PMID- 9229551
TI  - [The synchronous occurrence of acute myeloid leukemia and kidney carcinoma].
AB  - HISTORY AND CLINICAL FINDINGS: During the past year a 52-year-old man had
      developed quarterly bouts of fever, up to 38.5 degrees C, associated with fatigue
      and arthralgia. The fourth bout continued as undulating periods of fever with
      markedly impaired general state. Physical examination was unremarkable except for
      mild generalised lymphadenopathy. INVESTIGATIONS: Extensive imaging and
      serological studies failed to find an infectious or autoimmunological cause. But
      computed tomography and angiography revealed a space-occupying lesion in the left
      kidney, yet the suspected diagnosis of renal carcinoma insufficiently explained
      the clinical picture. DIAGNOSIS TREATMENT AND COURSE: Haematological tests having
      shown anaemia (Hb 8.1 g/dl) and blast cells (10%) in the peripheral blood a bone
      marrow biopsy was performed which indicated acute myeloid leukaemia. Three
      courses of intensive chemotherapy brought about only partial remission and the
      patient died 6 months later from a cerebral haemorrhage. An autopsy confirmed
      both the acute myeloid leukaemia and a renal carcinoma. CONCLUSION: The
      possibility of synchronous occurrence of two malignancies should always be kept
      in mind especially if the initially diagnosed tumor cannot explain the clinical
      symptoms.

PMID- 9229552
TI  - [Recurrent losses of consciousness in anaphylactic reactions].
AB  - HISTORY: Within one year a 36-year-old man had three episodes of loss of
      consciousness associated with a fall in blood pressure. No cause was established
      despite repeated hospital admissions. But an anaphylactic reaction was suspected
      as the cause after yet another syncope when the administration of antihistamines
      and steroids had quickly improved the patient's state. In retrospect it became
      clear that the loss of consciousness had occurred after the eating of bananas.
      INVESTIGATIONS: Total IgE level was 695 kU/l and there was marked sensitization
      to bananas (IgE radio-allergosorbent test [RAST] class 2) and latex (IgE RAST
      class 2), confirmed by marked immediate-type reactions to these substances in the
      prick test. PREVENTION: Dietary advice was given and the significance of the
      latex sensitization explained. The patient was given an allergy pass and drugs
      for emergency use. CONCLUSION: Anaphylactic reaction should be included in the
      differential diagnosis of loss of consciousness of uncertain cause. The prognosis
      of such a reaction is excellent only if treated at once. Both diagnosis and
      treatment are relatively simple.

PMID- 9229553
TI  - [Merkel cell tumor of the skin].

PMID- 9229554
TI  - [Naked DNA for inoculation and therapy].

PMID- 9229555
TI  - [Nuclear medicine diagnosis in the characterization of atherosclerotic plaques].

PMID- 9229556
TI  - [No authority of the health insurance plan for the general obtaining of medical
      opinion information in inpatient hospital treatment. The order of the Higher
      Social Court of Rheinland-Pfalz of 11 September 1995].

PMID- 9229557
TI  - [Cryofibrinogenemia caused by monoclonal antifibrinogen antibodies].

PMID- 9229558
TI  - [AIDS: David Ho's concept of virus elimination].

PMID- 9229559
TI  - [Formation, therapy and prevention of false aneurysm of the femoral artery
      following diagnostic and interventional heart catheterization].
AB  - OBJECTIVE: As pseudoaneurysm of the femoral artery after catheter introduction is
      a frequent complication, its causes and therapeutic options were investigated in
      a large patient collective. PATIENTS AND METHODS: In a prospective study with
      colour-Doppler duplex sonography of 6928 patients after diagnostic and of 3764
      after interventional cardiac catheterisation, pseudoaneurysms were diagnosed in
      80 patients (0.75%), 46 after diagnostic (0.66%) and 34 after interventional
      (0.9%) catheterisation. RESULTS: The incidence was higher in women than men
      (1.33% vs 0.58%; P < 0.05). Anticoagulation after sheath removal was the leading
      risk factor (n = 55, 68.8%), especially after interventional coronary
      intervention 85.3 vs 56.5%, P < 0.05). Local compression under duplex sonography
      monitoring was undertaken in 69 patients (86.3%), achieving aneurysmal
      obliteration in 53 (76.8%). Spontaneous thrombosis occurred in 15 of the
      remaining 27 patients, and surgical closure became necessary in 12. CONCLUSIONS:
      These data indicate a risk profile for the occurrence of pseudoaneurysm after
      cardiac catheterisation which can be dealt with by preventive measures. Local
      compression under duplex sonographic monitoring was the treatment of choice with
      a high success rate and low incidence of complications.

PMID- 9229560
TI  - [Primary sclerosing cholangitis with chronic pancreatitis].
AB  - HISTORY AND CLINICAL FINDINGS: A 68-year old man with insulin dependent diabetes
      mellitus was admitted to hospital because of diarrhoea, general weakness and 10
      kg weight loss over the preceding 3 months. Biliary tract enzymes were markedly
      elevated (alkaline phosphatase > 1000 U/l, gamma-glutamyl transferase > 300 U/l).
      Computed tomography (CT) was suggestive of a space occupying lesion in the head
      of the pancreas. INVESTIGATIONS: CT confirmed the space-occupying lesion and
      biopsy revealed chronic fibrosing pancreatitis. Radiology showed the typical
      picture of primary sclerosing cholangitis (PSC), in addition to inflammatory
      changes in the pancreatic duct. TREATMENT AND COURSE: Administration of
      ursodeoxycholic acid and substitution therapy for the exocrine and endocrine
      pancreatic insufficiency normalised the laboratory values. The patient gained 5
      kg and the changes in the biliary tract and pancreatic ducts markedly regressed.
      CONCLUSION: PSC is rarely associated with inflammatory pancreatic changes, which
      cause severe functional changes. Ursodeoxycholic acid improves both the
      biochemical changes and the histological lesions of the biliary tract and the
      pancreatic ducts.

PMID- 9229561
TI  - [Occlusion of finger arteries and thrombotic angiopathy of the retina during
      adjuvant tamoxifen therapy of a mammary carcinoma].
AB  - HISTORY AND CLINICAL FINDINGS: A 57-year-old woman had undergone partial
      mastectomy with subsequent radiotherapy for cancer of the breast. About 8 weeks
      after starting adjuvant treatment with tamoxifen (20 mg daily) pain, cooling and
      livid discoloration developed in her fingers and toes. Skin necroses over finger
      tips occurred and she was found to have visual field defects and double images.
      INVESTIGATIONS: There was no clinical or laboratory evidence of recurrence of the
      breast cancer. Tests of clotting and for inflammatory disease and complement
      levels were within normal limits. The antinuclear antibody titre was low (1:320)
      and the measured value of the rheumatoid factor reached the fourfold of normal
      level. Ophthalmoscopy revealed signs of retinal ischaemia, unilateral
      papilloedema, reduced visual acuity, visual field and abduction weakness. Duplex
      sonography and angiography demonstrated multiple occlusions of the finger
      arteries. TREATMENT AND COURSE: After tamoxifen had been discontinued and
      prostaglandin E1 administered (40 micrograms over one hour twice daily for 21
      days) the symptoms rapidly and markedly improved, the necroses of the finger tips
      healed and the ophthalmoscopic changes regressed almost completely. CONCLUSION:
      Tamoxifen, by inducing thrombophilia, can cause thromboembolic occlusions of
      peripheral arteries, and must in that case be discontinued.

PMID- 9229562
TI  - [Sleep apnea syndrome. Differential diagnostic reflections from the point of view
      of sleep medicine].

PMID- 9229563
TI  - [Prognosis factors in stomach carcinoma].

PMID- 9229564
TI  - [Epicondylitis of the radial humerus].

PMID- 9229565
TI  - [Loeffler's parietal fibroplastic endocarditis].

PMID- 9229566
TI  - [Fatty liver hepatitis].

PMID- 9229567
TI  - [Crystalluria and nephrolithiasis during therapy with the protease inhibitor
      indinavir].

PMID- 9229568
TI  - Parasites of the recently established round goby (Neogobium melanostomus) and
      tubenose goby (Proterorhinus marmoratus) (Gottidae) [corrected] from the St.
      Clair River and Lake St. Clair, Michigan, USA.

PMID- 9229569
TI  - Endoparasitic helminths of the European eel, Anguilla anguilla, from four
      disconnected meanders from the rivers Leie and Scheldt in western Flanders,
      Belgium.
AB  - The endoparasitic helminth communities of the European eel, Anguilla anguilla
      (L.), were investigated in four meanders, cut off from the rivers Leie and
      Scheldt in western Flanders, Belgium. Six species of helminths (2 cestodes, 2
      nematodes and 2 acanthocephalans) were found. The dominant parasite species was
      the nematode Anguillicola crassus (Kuwahara, Niimi et Itagaki, 1974) infecting
      79% of the eel population with intensities up to 112 specimens per fish. At two
      localities no acanthocephalans could be found, whereas these parasites were very
      common at the other sites. The prevalence, mean intensity, intensity and
      abundance, their correlation to the body length, and the frequency distributions
      were analysed. The site selection of parasites is in relation to food composition
      and feeding habits of eels, physiological and structural differences in the
      intestine and possible interspecific competition were discussed.

PMID- 9229570
TI  - The distribution of the metacercariae of Diplostomum phoxini in the brain of
      minnows, Phoxinus phoxinus.
AB  - Quantitative data are presented on the spatial distribution of metacercariae of
      the digenean trematode Diplostomum phoxini (Faust, 1918) in the brains of
      minnows, Phoxinus phoxinus (Linnaeus, 1758), from two Scottish populations.
      Sequential examination of serial histological sections revealed metacercariae to
      be unevenly distributed throughout the brain, aggregating in specific regions
      including the cerebellum, the medulla oblongata and the optic lobes. In addition,
      a number of metacercariae were found in the anterior part of the spinal cord. The
      inferior lobe of the cerebellum, pituitary, olfactory lobes and olfactory bulbs
      were largely free of metacercariae. Reasons for the uneven distribution of
      metacercariae within the brains of infected minnows are discussed, including the
      possibility that the parasite may have evolved to enhance its transmission to
      subsequent hosts by aggregating in regions known to be important in the control
      of the host's antipredator responses.

PMID- 9229571
TI  - Intense infections with a variant of Myxobolus procerus (Myxosporea) in muscle of
      trout-perch (Percopsis omiscomaycus) in Duluth Harbor, Lake Superior.
AB  - Intense infections of a variant of Myxobolus procerus (Kudo, 1934) are described
      from trout-perch (Percopsis omiscomaycus (Walbaum)) collected in Duluth Harbor,
      Lake Superior, USA. This particular population of parasites has spores that are
      identical in shape (narrow pyriform) to those described for M. procerus except
      that they are significantly smaller (13-14.5 microm long versus 15-17 microm
      long). In contrast to what was originally described for M. procerus, the
      plasmodia develop primarily within red and white striated muscle fibres and only
      rarely among the subdermal connective tissue. Most plasmodia were at or near the
      same stage of development. Typical development involves growth within the fibre.
      The parasite eventually replaces the entire content of the host cell and appears
      to halt development before rupturing the outer cell membrane. The only obvious
      host response was an occasional cyst being invaded by a localized cellular
      infiltrate. Infected fish appeared of normal health and no grossly evident
      myoliquefaction was seen. The infections involved several hundred plasmodia per
      fish and the question of why such unusually high levels of infection would
      develop in hosts inhabiting a polluted habitat is raised. It is suggested that
      proliferation of a pollution tolerant oligochaete (the suspected alternate host)
      in the harbour and/or a compromised host immune system may have increased the
      probability of successful transmission and development in trout-perch living in
      the harbour.

PMID- 9229572
TI  - Introduction to eicosanoids and the gastroenteric tract.
AB  - Eicosanoids are produced throughout the gastrointestinal tract and are
      significant mediators of physiologic and pathophysiologic processes.
      Understanding the precise role(s) of specific eicosanoid metabolites remains a
      significant challenge, but has led to the development of new pharmacologic
      strategies for treating NSAID-induced gastroenteropathy and IBD. Given the
      complex array of arachidonic acid metabolites, the development of more specific
      and potent inhibitors of these cyclooxygenase isoforms is important for future
      studies and possible therapeutic applications. Mice have been prepared that lack
      expression of COX-1 or COX-2. Once these animals have been carefully evaluated,
      understanding of the role of various pathways of eicosanoid formation in
      gastrointestinal function, development, and epithelial growth regulation might be
      improved. Considerable progress has been made in the understanding of arachidonic
      acid metabolism and in eicosanoid receptor biology. The identification and
      characterization of an inducible cyclooxygenase isoform has led to important
      studies evaluating the role of this enzyme in inflammation, neoplasia, and NSAID
      induced gastrointestinal injury. The demonstration that COX-2 overexpression in
      intestinal epithelial cells leads to specific phenotypic changes, such as
      increased adhesion and inhibition of apoptosis, indicates that this enzyme may
      alter the tumorigenic potential of epithelial cells and offers hope for the
      future development of improved chemopreventive agents.

PMID- 9229573
TI  - NSAIDs, gastrointestinal injury, and cytoprotection.
AB  - Gastrointestinal toxicity caused by nonsteroidal anti-inflammatory drugs (NSAIDs)
      is the most frequent drug side effect in the United States. NSAIDs are implicated
      in the development of complicated peptic ulcer disease and injury to the small
      bowel and colon. NSAIDs interfere with prostaglandin-mediated epithelial defense
      mechanisms and also cause direct epithelial toxicity. Current and future
      approaches to the prevention and management of NSAID injury are reviewed.

PMID- 9229574
TI  - NSAIDS and the microcirculation of the stomach.
AB  - In this article, the effect of NSAIDs on the gastric mucosal microcirculation was
      reported. Although the precise mechanism of NSAID-induced ulcerogenesis is still
      unknown, most NSAIDs have been shown to impair gastric mucosal microcirculation
      and cause gastric mucosal damage.

PMID- 9229575
TI  - Eicosanoids and inflammatory bowel disease.
AB  - IBD is a disease of unknown cause that involves an amplification of the
      inflammatory response in the intestinal mucosa. Although not the only offending
      agents leading to the disease, eicosanoids, the collective group of AA
      metabolites, may a significant role in the pathogenesis of IBD. This article
      reviewed the biochemical pathways of eicosanoid formation and the clinical
      relevance of eicosanoids to IBD. Potential strategies designed to interfere with
      various aspects of AA metabolism were also outlined. Further clinical trials of
      newer compounds may soon prove them effective in the management of IBD.

PMID- 9229576
TI  - NSAID use and decreased risk of gastrointestinal cancers.
AB  - The accumulating evidence suggests that aspirin or other NSAIDs may prevent or
      inhibit the development of colon and perhaps other digestive tract cancers.
      Although the clinical, experimental, and epidemiologic evidence is promising, the
      hypothesis remains unproven except in the models of chemically induced colon
      cancer in rodents and adenomatous polyps in patients with FAP. Clinicians should
      await the results of randomized trials before using NSAIDs for cancer prevention
      or treatment. Recommendations are as follows: 1. Experimental studies should
      define the mechanism or mechanisms by which NSAIDs inhibit tumorigenesis in the
      rodent model. 2. Experimental and clinical studies should define the optimal
      drug, dosage, and treatment regimen. The new, selective COX-2 inhibitors should
      be studied for efficacy and toxicity. 3. Epidemiologic studies should continue to
      explore the issues of dosage, duration, drug, and toxicity. Because full-scale,
      randomized trials are feasible only for studying intermediate end points such as
      polyp recurrence or proliferative indices in high-risk populations, epidemiologic
      studies have an ongoing role. 4. Carefully designed randomized, clinical trials,
      now underway, are needed to test the efficacy of NSAIDs in inhibiting colorectal
      polyps or cancer in humans. 5. Better criteria are needed as to who should take
      aspirin and who should not.

PMID- 9229577
TI  - NSAID-induced polyp regression in familial adenomatous polyposis patients.
AB  - NSAIDs inhibit prostaglandin synthesis. In 1983, Waddell et al first reported
      that sulindac, a NSAID (Clinoril), caused regression of rectal adenomatous polyps
      in several patients with familial adenomatous polyposis, an inherited form of
      colorectal cancer. Subsequently, NSAIDs have been used as chemopreventive agents
      in animal carcinogenesis models and adenoma regression had been confirmed in
      human trials with sulindac. This article summarizes these developments and
      describes possible mechanisms of colorectal neoplasia chemoprevention.

PMID- 9229578
TI  - Cyclooxygenase-2 inhibitors: a new class of anti-inflammatory agents that spare
      the gastrointestinal tract.
AB  - The NSAIDs are potent anti-inflammatory and analgesic agents. It is now believed
      that the NSAIDs exert their therapeutic activity through the inhibition of COX-2
      at the site of inflammation. Unfortunately, these compounds are equally capable
      of inhibiting constitutively expressed COX-1 in tissues such as the
      gastrointestinal tract and kidney, which results in serious, mechanism-based
      toxicities that limit the drug's therapeutic utility. With the identification of
      selective COX-2 inhibitors, alternatives to traditional NSAID therapy should be
      available that will provide clinical usefulness with reduced toxicity.

PMID- 9229579
TI  - The risks and costs of upper gastrointestinal disease attributable to NSAIDs.
AB  - NSAIDs, including both aspirin and nonaspirin NSAIDs, are among the most
      frequently used drugs, and their use may result in serious adverse
      gastrointestinal outcomes and significant medical costs. The increased risks for
      adverse upper GI hemorrhage and peptic ulcer disease associated with NSAID use
      have been demonstrated in observational studies and clinical trials; an overview
      of these results is presented in this article. The magnitude of these risks
      should play an important role in clinical decision making and should influence
      decisions regarding the use of this class of drugs.

PMID- 9229580
TI  - Prostaglandins in liver disease and liver transplantation.
AB  - This brief review summarizes the physiology and pharmacology of eicosanoids and
      describes how they have been tested for possible application in liver disease and
      transplantation. The objective is to trace the stepwise application from the
      laboratory to the bedside. Although many questions remain to be answered, the
      observations summarized in this article have opened up new and potentially
      rewarding prospects in application to liver disease.

PMID- 9229581
TI  - Isoprostanes--prostaglandin-like compounds formed in vivo independently of
      cyclooxygenase: use as clinical indicators of oxidant damage.
AB  - F2-isoprostanes are prostanoids produced independently of cyclooxygenase by free
      radical-catalyzed peroxidation of arachidonic acid-containing lipids.
      Quantification of F2-isoprostanes from biologic fluids and tissues represents an
      important advance in the detection and measurement of lipid peroxidation in vivo.
      In addition, efforts to understand both the biophysical effects of isoprostane
      containing lipids and the biologic effects of free isoprostanes should lead to a
      better understanding of the mechanisms responsible for oxidant stress-related
      alterations in homeostasis. Continued application of F2-isoprostane measurement
      in experimental models of free radical-induced injury and human disease may allow
      better design and evaluation of antioxidant therapeutic strategies.

PMID- 9229582
TI  - Inaugural address. Ethics in the third millennium.

PMID- 9229583
TI  - Reducing dietary fat: putting theory into practice. Symposium proceedings. New
      York, New York, December 10-11, 1996.

PMID- 9229585
TI  - OMERACT III. Outcome Measures in Arthritis Clinical Trials. Cairns, Australia,
      April 16-19, 1996. Proceedings.

PMID- 9229584
TI  - Visual hallucinations.

PMID- 9229586
TI  - Role of Hematopoietic Stem Cell Transplantation for Autoimmune Diseases.
      Proceedings of a conference. Seattle, Washington, October 27, 1995.

PMID- 9229587
TI  - Edema: pathophysiology and therapy. The Telesio Conference. Consenza, Italy,
      October 21-22, 1996. Proceedings.

PMID- 9229588
TI  - [Indications for eye muscle operations in adult patients].

PMID- 9229589
TI  - [Temporal trends in the etiology of blindness].
AB  - INTRODUCTION: Blindness prevention is a primary goal in ophthalmology. The long
      term success (in some respect) is reflected by the development of causes of
      blindness (e.g. in the interspeciality problem area of diabetic blindness). In an
      attempt to study long term developments in blindness epidemiology the German
      Committee for the Prevention of Blindness initiated the present study. MATERIALS
      AND METHODS: The present investigation reviewed (nearly) all German population
      based studies on the epidemiology of causes of blindness. Thus 35 studies
      covering more than 100 years have been included. Timely trends have been
      investigated by comparing relative frequencies of the prevalence of causes of
      blindness. RESULTS: Blindness prevalence increased in Germany during the
      historical observation time (present prevalence 138/100.000). The relative
      frequency of macular degeneration (presently the most frequent cause of blindness
      with approx. 15-20% share), diabetic retinopathy (present share approx. 5-7%) and
      high myopia (present share approx. 12-17%) have increased. The relative frequency
      of glaucoma (present share approx. 15%), tapetoretinal degenerations (present
      share approx. 5-10%) and retinal detachment (present share approx. 5-10%) have
      been more or less stable in the historical perspective. Cataract (present share
      approx. 5-10%), optic atrophy (present share approx. 5-10%), trauma (present
      share approx. < 5%), uveitis (present share approx. < 5%) and infections
      (presently only single cases) have diminished. DISCUSSION: Blindness prevalence
      has slightly increased in Germany over the last 100 years. Infections, traumas
      and uveitis have virtually disappeared as a cause of blindness. Macular
      degeneration, glaucoma and high myopia, on the other hand are increasingly
      responsible for blindness in Germany. CONCLUSION: From a preventive medicine
      standpoint the latter mentioned diseases should have priority in ophthalmologic
      research.

PMID- 9229590
TI  - [Use of a new optoelectronic vision aid for highly visually handicapped
      patients].
AB  - A new low vision aid (LVA)-the Low Vision Enhancement System or LVES, which were
      as developed at the Johns Hopkins University in Baltimore, is now commercially
      available. This instrument allows a magnification up to 10 times with control of
      contrast and luminance while the field of view is very large: 60 x 40 degrees. We
      present first results concerning LVES in comparison to conventional LVAs.
      PATIENTS AND METHODS: 60 consecutive patients suffering from macular dystrophy,
      macular degeneration, optic atrophy, tapetoretinal degeneration, or diabetic
      retinopathy were included in this study. We compared visual acuity with glasses,
      with telescope and using LVES. Furthermore we compared contrast acuity by the use
      of the Pelli-Robson-charts as well as the subjective impression of the patients.
      RESULTS: Improvement of visual acuity with LVES compared to correction with
      glasses was 8 log steps on average and up to 3 steps as compared to the use of
      telescopes. More important is the improvement of contrast sensitivity (0-16
      steps) and the reduced glare. Despite the subjective improvement of visual acuity
      and contrast sensitivity the majority of patients could not imagine to use LVES
      regularly. A significant improvement as compared to conventional low vision aids
      is possible for special applications such as office work, recognition of faces or
      images or for looking at a blackboard. CONCLUSION: In addition to traditional
      LVAs, the Low Vision Enhancement System opens up possibilities for a very small
      group of patients. Especially patients suffering from macular dystrophy or Lebers
      optic atrophy may benefit from this new system. The most important advantage of
      LVES is the improvement of contrast sensitivity and the significantly decreased
      glare sensitivity. Additionally the near working distance is changeable. The
      variable magnification allows an easier fitting to various tasks. Prior to the
      prescription of LVES a detailed and time consuming testing is necessary.

PMID- 9229591
TI  - [Dark adaptation for evaluating visual performance at twilight using the
      Trendelenburg eyeglasses].
AB  - Dark adaptation for testing visual acuity under mesopic conditions can be
      accomplished with Trendelenburg spectacles. The spectacle frames are in contact
      with the facial skin at all points, forming a light-tight seal so that no stray
      light reaches the eyes. The lenses are red filters, admitting no light below 630
      nm. When these spectacles are used, adaptation can be performed in a normally lit
      room.

PMID- 9229592
TI  - [Papular xanthoma of the eyelids].
AB  - BACKGROUND: Xanthomatous tumors are common tumors of the eyelid. We report the
      rare case of a patient with a papular xanthoma of the eyelid. CASE REPORT: The 87
      year old patient suffered from multiple xanthomatous lesion in the face and the
      trunk. The tumors were painless and elastic. A biopsy of the largest tumor was
      performed. RESULTS: The histologic examination revealed multiple histiocytes and
      giant cells of the Touton type. Immunohistochemistry showed a positive stain for
      CD68. CONCLUSIONS: The clinical, histologic and immunohistochemical findings are
      typical for a papular xanthoma and help to differentiate from other xanthomatous
      lesions such as xanthelasma, xanthoma disseminatum, necrobiotic xanthogranuloma
      and fibrous histiocytoma.

PMID- 9229593
TI  - [Aicardi syndrome and acquired retinal detachment].
AB  - BACKGROUND: The Aicardi syndrome is a complex of congenital anomalies consisting
      of agenesis of the corpus callosum, infantile spasms and pathognomonic
      chorioretinal lacunar lesions. An acquired detachment of the retina was reported
      only in one patient. HISTORY AND SIGNS: We report about a nine-month-old girl
      with Aicardi syndrome. She presented the typical signs of this syndrome and an
      acquired detachment in both eyes. THERAPY AND OUTCOME: We performed a translimbal
      vitrectomy with silicon-oil instillation on the right eye. CONCLUSION: On the
      basis of histological findings reported in the literature we suggest a combined
      pathogenesis of the ablatio retinae in our patient with Aicardi syndrome:
      traction and foramina.

PMID- 9229594
TI  - [Granular cell tumor of the eyelid].
AB  - A 54-year-old woman was evaluated for a right lower eyelid lesion that had been
      present for four months. Examination showed a firm, yellow to brown mass with
      associated loss of eyelashes. A complete resection of the lesion was performed
      and the lid was reconstructed with the Hughes procedure. Histologic features of
      the excised mass were consistent with a granular cell tumor. Immunohistochemical
      stains were positive for S-100 protein, neuron specific enolase, laminin, and
      various myelin proteins in the tumor cells. Ultrastructural examination displayed
      that tumor cells were distended by autophagic granules and some cells contained
      angulated bodies (Bangle bodies). Granular cell tumors probably origin from
      Schwann cells and rarely involve the eyelids.

PMID- 9229596
TI  - [Contact glass dynamometry].

PMID- 9229595
TI  - [Corneal lipofuscinosis--clinicopathologic study of 10 patients].
AB  - BACKGROUND: Lipofuscin pigments are considered indigestible residues of lysosomal
      activity associated with aging. We present the clinical and histopathological
      features of ten patients with corneal lipofuscinosis. PATIENTS AND METHODS: Ten
      patients (five female, five male, mean age 62 years, range 53 to 77 years)
      underwent penetrating keratoplasty for vascularized corneal scars. The clinical
      diagnoses were herpes simplex keratitis (5), zoster keratitis (1), phlyctenular
      keratitis (1), immunologic graft rejection (2) and corneal injury (1). The mean
      duration of disease was 6.5 years (range 3 to 11 years). On slit lamp examination
      both linear and diffuse deposits of yellow pigment were noted in the corneal
      stroma. All corneal buttons were processed for histopathologic and electron
      microscopic studies. RESULTS: The areas of yellowish pigmentation in the corneal
      stroma corresponded histopathologically to clusters of macrophages, keratocytes
      and occasional giant cells containing PAS-positive granules. The granules
      measured 1 to 3 micrometers and were also present extracellularly. Results of
      Gram stain were negative, but the material showed vivid autofluorescence.
      CONCLUSION: Corneal lipofuscin can be detected at the slit lamp as focal or
      diffuse yellowish deposits in both the superficial and deep corneal stroma of
      patients with long-standing keratitis. This is in contrast to corneal iron
      deposits, which appear as yellowish pigment in the corneal epithelium. The
      identification of corneal lipofuscin is possible using histochemical and
      autofluorescent studies. Further studies should address whether corneal
      lipofuscin predisposes to suture loosening.

PMID- 9229597
TI  - [Pericorneal vascular changes as an expression of systemic vascular processes].
AB  - BACKGROUND: To evaluate the extent of morphological changes of the perilimbal
      vessels of the conjunctiva in patients with general vascular disorders. MATERIALS
      AND METHODS: With a questionnaire systemic vessel diseases were investigated in
      285 patients (m:f = 145:140; mean age = 54 +/- 19 years) with pericorneal vessel
      alterations. Persons without any morphological alteration of the perilimbal
      vessels served as control group (n = 58; m:w = 44:14; mean age 26 +/- 13 years).
      RESULTS: In the patient group we found the following pericorneal vessel
      alterations: vessel ectasia in 79%, vessel aneurysm in 41%, vessel interruptions
      in 37% and avascular regions in 12%. The distribution of the three most frequent
      systemic vascular processes in the patient/control group was: peripheral vascular
      spasm (cold hands and/or feet) in 57%/19%, migraine in 39%/14% and arterial
      hypertension in 33%/3%. CONCLUSION: Alterations in perilimbal vessels seem to be
      correlated with systemic vascular disorders. In case of perilimbal vascular
      anomalies an internal medical examination should be considered.

PMID- 9229598
TI  - [Ultrasound biomicroscopy as a criterium of functional assessment of the supra
      choroidal cleft after chamber angle surgical interventions].
AB  - BACKGROUND: The new technique of ultrasonic biomicroscopy provides detailed
      information about the extension and width of suprachoroidal clefts during the
      follow-up period after cyclodialysis ab interno. PATIENTS AND METHODS: We
      examined a group of 9 patients suffering from dysgenetic glaucoma and secondary
      glaucoma. Ultrasonic biomicroscopy was performed before and after cyclodialysis
      ab interno. The results were compared to those of gonioscopy. RESULTS: These
      examinations revealed that even cyclodialysis clefts which appeared to be closed
      by gonioscopy were still open. This was proven by a broad choroidal cleft in the
      cyclodialysis area. CONCLUSIONS: Thus, ultrasonic biomicroscopy is a means of
      checking the outcome of cyclodialysis ab interno and may influence the
      indications for further surgical procedures.

PMID- 9229599
TI  - [Tectonic epikeratoplasty as an alternative to keratoplasty a chaud?].
AB  - PURPOSE: To compare the outcome of epikeratoplasty vs. penetrating keratoplasty
      in patients with corneal ulcer. PATIENTS AND METHODS: 24 patients had been
      treated by an epikeratoplasty and 20 patients by a penetrating keratoplasty
      within 5 years. The indication to operate was progression of a corneal ulcer,
      perforated ulcer or a descemetocele. In epikeratoplasty a complete cornea with
      adjacent scleral rim was fixed upon the recipient eye by scleral sutures. This
      transplant was removed after some weeks. In both groups the patients were
      reexamined and the anatomical and functional outcome was registered. RESULTS: In
      both groups all but one globe could be saved. The integrity of corneal surface
      was restored in 85% (n = 17) of the keratoplasty group and in 75% (n = 18) in
      epikeratoplasty. The vascularization of the cornea after removing the transplant
      in epikeratoplasty patients was increased by 70% (n = 17) and their corneas
      revealed more opacification than before. In the penetrating keratoplasty patient
      group the vascularization increased in 40% (n = 8) and in 20% (n = 4) of the
      patients the transplant became cloudy. The visual acuity improved in 13 cases in
      penetrating keratoplasty but only in two cases after epikeratoplasty. CONCLUSION:
      A corneal ulcer (with or without perforation) treated by a penetrating
      keratoplasty with removing the ulcerated tissue has a better outcome than an
      ulcer covered by an epikeratoplasty. In patients only able to tolerate a short
      time of surgery with minimal operative risk or if there is no possibility of
      microsurgical treatment epikeratoplasty may be an alternative to penetrating
      keratoplasty in saving the globe. However, in most patients penetrating
      keratoplasty has better functional results.

PMID- 9229600
TI  - [Endothelial cell loss after phacoemulsification with the "reversed tip and snip"
      technique compared with the "divide and conquer" technique].
AB  - BACKGROUND: The endothelial cell count after phakoemulsification is a sensitive
      parameter to compare different phakoemulsification techniques. PATIENTS AND
      METHOD: In a prospective study 30 patients in each group were operated upon the
      "Reversed Tip and Snip" and with the "Divide and Conquer"-Technique. The corneal
      endothelial cell count was measured before surgery and 4 weeks and 3 months after
      the operation. RESULTS: The endothelial cell count was reduced significantly
      about 10% after the the "Reversed Tip and Snip" and about 15% after the "Divide
      and Conquer"-Technique. The first mentioned technique had a significantly reduced
      cell loss than the latter. CONCLUSION: The "Reversed Tip and Snip"
      phakoemulsification technique causes less endothelial cell loss than the "Divide
      and Conquer"-Technique.

PMID- 9229601
TI  - [Measuring depth perception in stereoamblyopia by using a suprathreshold
      stimulus].
AB  - BACKGROUND: Stereotests based on random distribution pattern (global stereopsis)
      show disadvantages when giving larger disparation, because subjects with limited
      fusion-ability do not recognize them, while realistic shapes of objects (contour
      stereopsis) are usually fused. Because of this random dot tests can not always be
      utilized to verify subnormal stereo-ability. SUBJECTS AND METHODS: This paper
      describes a way of testing stereo-ability not by approaching stereo-angle
      thresholds but by presenting supra-threshold stimuli and evaluating the
      emphasized subjective "elevation level" readings. With this method I examined
      normosensoric healthy subjects and compared them to subjects with different
      binocular defects. RESULTS AND CONCLUSIONS: The subjective sensations correlate
      well with the clinical impression of what those patients, known at the department
      for long periods, should be able to differentiate. There is no evidence that
      healthy people are fully competent while "cured" strabismus cases should be
      incompetent. Indeed a gradual decrease of stereo-ability is seen. We strive for a
      really simple finger test in terms of subjective depth perception as a quick
      halfprecise office check.

PMID- 9229602
TI  - [Antazoline/tetryzoline eyedrops in comparison with levocabastine eyedrops in
      acute allergic conjunctivitis].
AB  - BACKGROUND: Allergic conjunctivitis is one of the most frequent allergic diseases
      of the anterior eye segment. METHODS: This multicentre, clinical trial was an
      investigation to compare the antiallergic efficacy, local tolerance and safety of
      Antazolin/Tetryzolin eye drops and Levocabastine eye drops. 69 patients were
      treated over a 2 weeks course of therapy. The subjective and objective ocular
      symptoms were documented over the treatment period. RESULTS: Both eye drops
      reduced subjective and objective ocular symptoms effective. The difference
      between the treatments (p = 0.0395) was the faster onset of action of
      Antazolin/Tetryzolin 30 minutes after administration of the first drop of trial
      medication. CONCLUSION: A fast and effective onset of action is of high clinical
      relevance. Therefore the benefits of using Antazolin/Tetryzolin eye drops was
      clearly outweigh.

PMID- 9229603
TI  - [The low vision cyclist: handicapped orientation and assessment with the
      nystagmogram].
AB  - BACKGROUND: Visually impaired individuals who are unable to obtain a driving
      licence may use a bicycle and feel fit for traffic as part of this "bio-physical
      model". MATERIALS AND METHODS: Five nystagmic amblyopes who claimed to ride a
      bicycle were tested in respect to visual acuity, peripheral vision and oculomotor
      functions. In three of these cases visual acuity amounted to 0.3, in one to 0.6,
      in another one only to 1/35. Eye movements were recorded by electro-oculography.
      The following qualities of gaze were determined: Fixation-saccadic eye movements
      pursuit eye movements-behaviour in light and dark-vestibulo-optokinetic movements
      eye positioning in resting states and influence of mood. RESULTS: In four of the
      cases oculomotor regularities were found. These were explained to the patients.
      One of the cases was affected with a form of chaotic nystagmus. CONCLUSION:
      Bicycling demands on both the vestibular and the visual system. Deficiencies
      relevant to behaviour in traffic and the possibilities to compensate for these
      may be estimated based on a oculographic evaluation. This should therefore be
      used to advise bicyclists with a visual impairment.

PMID- 9229604
TI  - [Mechanism of action and clinical effectiveness of immunomodulator
      glucosaminylmuramyl dipeptide (licopide)].

PMID- 9229605
TI  - [Differential diagnosis of heart valves changes in patients with bacterial
      endocarditis].

PMID- 9229606
TI  - [Exacerbation of hypertension and disturbances of the geomagnetic field].
AB  - The authors consider relationships between emergence of acute episodes of
      essential hypertension (hospital admittances) and disturbance of the geomagnetic
      field. The authors report male- and female-specific ranges of the geomagnetic
      field variations which are threatening for hypertensive subjects.

PMID- 9229607
TI  - [Late complications of combined therapy of lymphogranulomatosis].
AB  - Basing on the results of follow-up of 212 lymphogranulomatosis patients in long
      term remission, the authors have identified most frequent and serious
      complications. Contribution of different treatment components to development of
      these complications is specified. Signs of mono- and polyorganic lesions due to
      combined therapy are described, recommendations on the follow-up and prevention
      of the complications are provided.

PMID- 9229608
TI  - [Affection of myocardium in diabetes mellitus].
AB  - Echocardiography was performed in 67 patients with compensated diabetes mellitus
      (DM) type I and II. No signs of cardiovascular failure were noted. 20 patients
      have undergone myocardial scintigraphy. The patients were found to have
      hyperkinetic central hemodynamics resultant in DM type I from tachycardia, high
      rate of circulatory shortening of myocardial fibers, in DM type II from
      compensatory myocardial hypertrophy. In both diabetic types the function of
      myocardial relaxation was deteriorated as indicated by increased end diastolic
      volume and slow left ventricular relaxation. This evidences for initial cardiac
      failure. Myocardial scintigraphy registered perfusion defects in all the
      examinees, more profound in diabetes mellitus type II. The above findings explain
      the existence of marked coronarogenic and metabolic myocardial defects in DM.

PMID- 9229609
TI  - [Problems of differential diagnosis and prognosis of diabetes mellitus in
      adults].

PMID- 9229610
TI  - [Ultrasound findings in the zone of cholecystectomy and their role in prognosis
      of paralytic ileus development].
AB  - A comparative analysis of 112 patients' case histories with calculous
      cholecystitis has revealed that morphological alterations of the gallbladder wall
      and in the perevesicular area as well as the operative techniques are essential
      for the wound healing and ultrasound picture in cholecystectomy zone. Ultrasound
      investigation within postoperative 24 hours enables a significant prognosis of
      the onset of intestinal paresis, its severity and duration. This is important for
      conducting early prophylactic measures.

PMID- 9229611
TI  - [Thyroid gland and thyroid status in patients with chronic liver diseases].

PMID- 9229612
TI  - [High density lipoproteins composition in leg amputees].

PMID- 9229613
TI  - [Effects of eifitol on lipid metabolism in patients with clinically different
      ischemic heart diseases].

PMID- 9229614
TI  - [Syndrome X].

PMID- 9229615
TI  - [Efficacy of cordipin chronotherapy with reference to anginal patients'
      chronosensitivity].
AB  - A randomized trial has been conducted of cordipin conventional treatment versus
      chronotherapy in 40 patients with coronary heart disease, angina pectoris (class
      II and III), progressive angina. The patients entered 2 groups. Group 1 have
      received conventional treatment with cordipin in a dose 10 mg 3 times a day,
      group 2 patients received cordipin once a day in a dose 10 mg depending on their
      chronosensitivity to this drug, i.e. in the period of the highest hemodynamic
      activity of cordipin. Chronosensitivity to cordipin was determined in acute
      clinicopharmaceutical tests once a day for 4 days. As shown by chest tetrapolar
      rheography, echocardiography, exercise tolerance chronotherapy is effective
      because the antianginal effect was achieved 2 times more rapidly with 3 times
      reduced daily and course doses. Moreover, more potent hemodynamic support of the
      antianginal effect is provided.

PMID- 9229616
TI  - [Eating behavior abnormalities of psychosomatic origin in medical practice].

PMID- 9229617
TI  - [Meningeal syndrome in differential diagnosis of infectious diseases].

PMID- 9229618
TI  - [Diarrhea and constipation].

PMID- 9229619
TI  - [On diagnostic value of Whipple's triad: a case of insulinoma diagnosis].

PMID- 9229620
TI  - [Occupational diseases features and priorities in internal medicine].

PMID- 9229621
TI  - [Gastroduodenal lesions induced by non-steroidal antiinflammatory drugs].

PMID- 9229622
TI  - [Lymphogranulomatosis: current problems of clinical presentation, diagnosis and
      treatment].

PMID- 9229623
TI  - [Alcohol and stomach].

PMID- 9229624
TI  - [The role of nitric oxide in cardiology and gastroenterology].

PMID- 9229625
TI  - [New approaches to diagnosis and treatment of cholelithiasis in young
      occupational groups].
AB  - Cholelithiasis was treated in 107 pilots. Cholesterol choleliths were effectively
      treated with ursosan. In bilirubin or calcium stones ursosan combination with
      shock-wave lithotripsy is more effective. Promising is dissolving of the stones
      in the gall bladder by chemical solvents delivered through special drainage or
      catheters. In lithogenic bile it is recommended to conduct early prophylaxis of
      the stones with ursodeoxycholic acid compounds.

PMID- 9229626
TI  - [Characteristic of oxidative metabolism and microsomal enzyme system of the liver
      in patients with chronic circulation insufficiency].
AB  - The examination of 52 patients with circulation insufficiency class II-III (CI)
      provided evidence on suppressed monooxygenase system of the liver brought by
      lipid peroxidation (LPO) activation in CI of different etiology. The severity of
      the above changes was related to CI class. LPO intensification weakens anti
      oxidant defense and promotes enhancement of endogenic intoxication. The latter
      becomes most pronounced in CI of the III degree.

PMID- 9229627
TI  - [Changes of hemostasis in patients with acute hepatitis B and hepatic
      encephalopathy].

PMID- 9229628
TI  - [Essential aspects of differential diagnosis of coronarogenic and non
      coronarogenic myocardial lesions].

PMID- 9229629
TI  - [Fractional plasmapheresis in therapeutic experience: methodological approach].
AB  - The aim of the study was estimation of the incidence rate of complications
      arising in the course of fractional plasmapheresis (FPA), the analysis of their
      causes and design of prophylactic measures. 139 courses comprising 410 FPA
      sessions were delivered in 118 patients with various diseases. The highest rate
      of complications was 4.7%. If put on FPA without previous preparation, the
      patient experienced marked hypotension because of fast escape from circulation of
      500 ml of blood. Induction of short-term hypervolemia in patients with low
      arterial pressure prevents emergence of cardiovascular complications in the
      course of blood exfusion.

PMID- 9229630
TI  - [Administration of energostim in severe chronic cardiac failure due to alcoholic
      damage of heart].

PMID- 9229631
TI  - [Coronary heart disease: current status and prospects for the future].

PMID- 9229632
TI  - [Medications permitted for practical use by the RF Ministry of Health].

PMID- 9229633
TI  - [Ascites].

PMID- 9229634
TI  - [Treatment patients with ascites].

PMID- 9229635
TI  - [Hypothalamic hereditary diabetes insipidus in four generations].

PMID- 9229636
TI  - [A case of diagnosis of common variable immunodeficiency (CVID)].

PMID- 9229637
TI  - [Antiphospholipid syndrome].

PMID- 9229638
TI  - [Problem of diagnostic search in view of psychologic decision theory].

PMID- 9229639
TI  - [The analysis of R-R intervals variability in assessment of autonomic regulation
      of cardiac rhythm (review of some data reported at the XVII and XVIII Congresses
      of European Cardiology Society)].

PMID- 9229640
TI  - [History of organization and activities of Moscow Therapeutic Society].

PMID- 9229641
TI  - [Vladimir Kharitonovich Vasilenko (personal impressions)].

PMID- 9229642
TI  - [VK Vasilenko: some ideas in letters and communications (to his centenary
      birthday)].

PMID- 9229644
TI  - Proceedings of the 1st International Conference on Immunology and Aging.
      Bethesda, Maryland, June 16-19, 1996.

PMID- 9229643
TI  - [Helicobacter pylori: role in the onset of chronic gastritis and ulcer].

PMID- 9229645
TI  - [Landell traces Linne: physician and gardener].

PMID- 9229647
TI  - [Female physicians about their experiences from a national congress. They created
      strong networks in spite of contrary wind and suspicion].

PMID- 9229646
TI  - [Cooperation is task of the profession! High expectations put on consultants in
      general practice].

PMID- 9229648
TI  - [Is patient insurance something to count on?].

PMID- 9229649
TI  - [The AT-physicians should be guaranteed supervisory training].

PMID- 9229650
TI  - [Pay attention to the conditions of mentally ill in Russia!].

PMID- 9229651
TI  - [The generous administration of albumin].

PMID- 9229652
TI  - [Care of rheumatoid arthritis abroad is not comparable with hospital care].

PMID- 9229653
TI  - [Our role as physicians is to give service].

PMID- 9229654
TI  - [Virology. The art of controlling the geniality which even the smallest
      contagions show].

PMID- 9229655
TI  - [St John's wort against depression in favour again].
AB  - Extracts of Hypericum perforatum St. John's wort, have been used since antiquity
      for the treatment of depressive symptoms. In 25 controlled clinical trials where
      hypericum extract was compared with placebo and established antidepressants,
      improvement was obtained in 61 percent of patients on low-dose treatment (< 1.2
      mg hypericum extract), and in 75 percent of patients treated with a higher dose
      (2.7 mg). The side effects were mild and occurred at lower frequency than did
      those of other antidepressants. The constituent of hypericum extract that is
      responsible for the antidepressant effect has not been identified. Nor is the
      mechanism of action known, but a combination of low-grade monoamine oxidase
      inhibition and noradrenaline and serotonin reuptake blockade seems the most
      likely alternative, though other interesting mechanisms have also been proposed.
      Owing to their beneficial effect and low toxicity, preparations containing
      extracts from H perforatum might furnish an alternative to established therapy,
      especially among patients concerned about stigmatization or less apprehensive of
      herbal medication than of synthetic drugs.

PMID- 9229656
TI  - [Care of heart failure may be better].

PMID- 9229657
TI  - [New terminology for peripheral vascular malformations. A stringent
      classification is of advantage for the overall view].

PMID- 9229658
TI  - [Photodynamic therapy, laser therapy, brachytherapy, stents. Local control of
      lung cancer].
AB  - As only a small proportion of patients presenting with lung cancer can be cured,
      palliation has a very important place in their treatment. The local effects of
      lung cancer often entail substantial deterioration of the patient's quality of
      life. Recent advances in such techniques as laser treatment, brachytherapy,
      photodynamic therapy and prosthetic stents have enabled important improvements to
      be made in the control of lung cancer (both primary tumours and metastases).
      Laser treatment is mainly used to obtain bronchial patency rapidly, but needs to
      be followed up with other treatments. Photodynamic therapy is confined to the
      treatment of very small early cancers, but may be curative in such cases.
      Brachytherapy, the brief introduction of a source of radiation in the bronchi,
      may be effective both in endobronchial tumours, and in cases where there is
      compression due to a tumour outside the bronchi. The method can be used
      repeatedly, even in patients undergoing external beam radiation therapy. Finally,
      prosthetic stents are increasingly used to maintain bronchial patency, both in
      malignant and in certain non-malignant diseases. The achievement of optimal
      results often entails the use of a combination of the various methods, thus
      necessitating close cooperation between lung specialists, oncologists,
      radiologists, ENT surgeons and GPs.

PMID- 9229659
TI  - [A multicenter study shows alarming results. High antibiotic resistance within
      Swedish intensive care].

PMID- 9229660
TI  - [Treatment of acute urinary disorders. Simple tests and questions make the
      diagnosis and therapeutic choices easier].

PMID- 9229661
TI  - [Therapeutic results in rectal cancer surgery. Surgical technique is of great
      significance].

PMID- 9229663
TI  - [Fusion of clinics in Lund and Landskrona. Refined structure of work makes the
      surgery more efficient].

PMID- 9229662
TI  - [The nerve gas terrorist attack in Tokyo subway 1995. Cooperation during the
      relief work is necessary].

PMID- 9229664
TI  - [Standard demands concerning a new IUD are the same as for heart valves].

PMID- 9229665
TI  - Polly Matzinger: immunology's dangerous thinker.

PMID- 9229666
TI  - Court ruling means that Egypt embraces female circumcision again.

PMID- 9229667
TI  - Malaria outbreak hits refugees in Tanzania.

PMID- 9229668
TI  - Kuwait's health system charges look set to dissuade foreign workers.

PMID- 9229669
TI  - The signature of responsibility.

PMID- 9229670
TI  - [Genotoxicity of urban air particulate matter].
AB  - This paper reviews the genetic toxicology of urban air particulate. Dusts present
      in the urban environment are composed of a special type of soot, currently mainly
      emitted by motor vehicles. This soot contains variable quantities of adsorbed
      highly active genotoxic compounds (polycyclic aromatic hydrocarbons and their
      nitro derivatives, i.e., nitroarenes). Nitroarenes are among the compounds with
      the highest genotoxic activity according to the Ames test (genetic point mutation
      on bacteria), and are particularly abundant in ultrafine particulate matter (<
      1.1 microns) emitted by diesel engines, mainly trucks. Diesel emissions have been
      considered as probable carcinogenic agents for man by the International Agency
      for Research on Cancer (IARC). Highly mutagenic activity is present in the air of
      all the cities in the world, and there is increasing concern about possible
      carcinogenic effects on the general population as a result of exposure to urban
      particulate matter. Early epidemiological studies on city-dwellers exposed to
      heavy pollution indicate an excess of lung tumours. Lastly, there is a possible
      carcinogenic risk for occupationally exposed workers, such as traffic police and
      those working for city road cleaning services, etc., who are constantly obliged
      by their jobs to be exposed to polluted city air at work.

PMID- 9229671
TI  - [Environmental and biological monitoring of occupational exposure to
      perchloroethylene in dry cleaning shops].
AB  - Occupational exposure to perchloroethylene (PCE) was studied in a total of 106
      workers in 78 dry cleaning shops in the province of Pavia, Northern, Italy.
      Environmental monitoring was performed by personal passive sampling. The median
      time weighted average (TWA) level of PCE was 57 mg/m3, i.e., about 30% of the
      current Threshold Limit Value (TLV) proposed by the American Conference of
      Governmental Industrial Hygienists (ACGIH). However, in 12 workers exposure
      exceeded this limit. Biological monitoring was performed via measurement of
      urinary trichloroacetic acid (TCA), i.e. the exposure index currently used in
      Italy, and urinary excretion of unmodified perchloroethylene (PCE-U) in samples
      collected at the end of the half-shift. Median levels of TCA and PCE were 1.03
      mg/l and 17.7 micrograms/l respectively. The correlation coefficient between
      environmental TWA concentrations of perchloroethylene and PCE-U was 0.755 (0.809
      after logarithmic transformation), compared to 0.660 for TCA values. The subjects
      were then classified as "low exposed" and "heavily exposed" according to whether
      personal exposure was lower or higher than 57 mg/m3, the median TWA value of the
      whole group. PCE-U levels were significantly correlated to exposure in both
      subgroups whereas TCA was correlated only in the "heavily exposed subjects", but
      not in those with lower exposure. The results of the study show that in the
      majority of dry cleaning shops exposure to PCE was well below the current
      occupational limits. Nevertheless surveillance of dry cleaners is recommended as
      nearly 10% of the workers exceeded the environmental and biological limits.
      Urinary excretion of unmodified PCE appears to be a very reliable indicator for
      biological monitoring of PCE exposure in dry cleaning and is also significantly
      correlated to exposure at low levels. The estimated biological equivalent
      exposure level (BEEL) for PCE-U, corresponding to the current TLV-TWA proposed by
      the ACGIH, is 55 micrograms/l. Urinary TCA seems to be less suitable for
      assessment of individual exposure to perchloroethylene in dry cleaners as it is
      poorly representative of exposure to low levels of the solvent, which is a very
      common occurrence in this occupational group nowadays.

PMID- 9229672
TI  - [Occupational asthma: considerations on epidemiology and criteria of damage
      evaluation].
AB  - The authors review the available data on occupational asthma in Italy; it is
      estimated that 500-600 cases occur per year, although it is difficult to
      establish the real prevalence of this disease; it is in any case under estimated.
      The author also reviews the medical/legal criteria used for diagnosis and
      compensation purposes, and criteria are proposed for the assessment of residual
      permanent damage. This assessment should be based not only on the degree of
      bronchial obstruction (as in the case of pneumoconiosis and chronic bronchitis),
      but also on the degree of bronchial hyper-reactivity and the need to take drugs
      (mainly steroid drugs orally). As examples, the author quotes the guidelines of
      the American Thoracic Society and the compensation system in force in Quebec in
      Canada, where these aspects are adequately taken into account. Assessment of
      residual permanent damage can only be performed when the clinical conditions of
      the patient, the spirometry and bronchial hyper-reactivity levels are stabilized
      (usually two years after cessation of exposure to the agent responsible for the
      disease); otherwise the damage may be overestimated or a false underestimation
      may result. The author stresses the importance of medical rehabilitation and
      retraining of the occupational asthmatic if resumption of his former job, which
      caused the disease, is not feasible. Early diagnosis of occupational asthma is
      necessary not only in order to avoid clinical aggravation of the disease but also
      to limit the social and economic costs.

PMID- 9229673
TI  - [Noise exposure in a dry dock].
AB  - Personal monitoring of noise exposure was conducted in a small dry dock, where
      mainly tug-boats and high sea fishing-boats are refitted. Manual tools were the
      prevalent noise sources. Noise exposure could be affected and amplified by
      factors extraneous to workers' tasks. The workers might be employed in different
      jobs simultaneously also in confined and small areas, and were mainly involved in
      non-routine tasks. Six different tasks were investigated: dry-dock supervisor,
      welder/ship-wrights, painters, electricians, woodworkers and unskilled workers.
      The number of workers employed in the tasks, with the exclusion of the
      supervisor, might change from day to day according to the particular work phase
      carried out on the boat. Daily personal exposure was measured using Larson Davis
      mod. 700 integrating sound level meters. The all shift time history of short
      equivalent continuous sound level with 10 s integrating time was collected for
      each selected worker. A 1/2 inch microphone was attached to the helmet at a
      distance of 11 +/- 1 cm from the right outer ear. Measurements were repeated over
      13 days and randomly distributed over about four months. The number of data
      points collected was nine for the supervisor, twenty-seven for the welders,
      eighteen for the painters, twelve for the electricians, six for the woodworkers
      and eleven for the unskilled workers. Ranges of the daily noise exposure level
      were from 15 to 30 dBA for all tasks, with the exclusion of the woodworkers. The
      time histories relative to workers grouped in the same task were matched to
      verify the correlation. The daily exposure levels derived from correlated samples
      were substituted by their arithmetic mean. The analysis of variance applied to
      experimental distributions of daily exposure for four of the welders indicates
      that the difference of means (p > 0.3) is not significant. A similar conclusion
      is reached for painters when only this task is considered. If we take into
      account the exposures of painters employed also in different tasks, the
      probability is included in a range of lower significance, between 0.1 and 0.05.
      The experimental distributions of daily noise exposure for all tasks fit the
      normal distribution. The Kolmogorov-Smirnov test was used at a p > 0.1 confidence
      level. These results may have an important role in defining sampling strategies
      for collecting noise exposure data both for compliance and epidemiological
      purposes.

PMID- 9229674
TI  - [Indicators of dynamic work tolerability in healthy subjects].
AB  - This paper reports a study on the dynamics of tolerability in performing dynamic
      cycling in healthy subjects. Data on individually tolerable levels (power x
      duration) was obtained from 9 subjects by means of three submaximal tests on an
      ergometric bicycle lasting < or = 40 minutes, with constant load (50%, 65% and
      80% of maximum VO2 reached during a previous test of increasing difficulty within
      the limits of the symptoms). During performance of the test we monitored heart
      rate and subjective perception of fatigue (Borg's 10-point scale). We then
      defined the individual functions of "isoperception", which expressed the
      individual trend of the product "power x duration" at identical subjective
      perception score. On the basis of the metabolic parameters monitored, the
      individual isoperceptive functions at a "moderate" level of fatigue (3 on the
      Borg scale) were defined as "tolerability) threshold" for prolonged dynamic
      cycling. The product "power x duration" defined by the isoperceptive curves at a
      "moderate" level of fatigue does in fact reflect the individual aerobic capacity
      that can be sustained for prolonged dynamic activity (under 60 minutes). In order
      to validate the hypothesis of tolerability of the functions identified, three
      further short tests were performed (duration < or = 8.5 minutes) on an ergometric
      bicycle, with measurement of ventilatory and metabolic parameters.

PMID- 9229675
TI  - [Analysis of correlated data in occupational medicine: examples with binary
      data].
AB  - In a previous paper in this Journal we presented and discussed examples of
      analysis of correlated data when the response variable was continuous and
      normally distributed (the measurement of exposure to a toxic substance was the
      case in point). In this paper we extend the analysis and the discussion to take
      into account categorical (binary) variables (described in terms of proportions or
      odds); to favour the comprehension of the analogies (and discrepancies) between
      the two contexts we have fully developed an example that mimics the situation
      presented in the previous paper. Marginal, conditional, random effects and
      transitional models for correlated data are introduced in practical terms; the
      meaning of the different estimates obtained are interpreted for epidemiological
      purposes; the disadvantages of not considering correlation in the analysis are
      explained and the complexities connected to this type of analysis are fully
      appreciated. It is concluded that correlated data are very frequently encountered
      in occupational settings and that an appropriate analysis is necessary. This
      analysis requires sophisticated computer programs and statistical expertise,
      particularly in the case of categorical data.

PMID- 9229676
TI  - [Prevention of occupational risks and residual powers of investigation by work
      inspectors. Abnormal situations and penal solutions].

PMID- 9229677
TI  - [Muscular and bone disorders and hearing loss as diseases created by man: the
      primate of prevention].

PMID- 9229678
TI  - [A simple model of the optimal time for allogenic bone marrow transplantation in
      chronic granulocytic leukemia].
AB  - Allogenic bone marrow transplantation is the treatment of choice in chronic
      granulocyte leukemia patients, while the best results are achieved when it is
      performed in the chronic phase of the illness. That is why time optimization for
      bone marrow transplantation in chronic granulocyte leukemia means making priority
      lists for transplantation according to medical indications. This study comprises
      a very simple model of optimal time for bone marrow transplantation in chronic
      granulocyte leukemia. It is based on data of the International Bone Marrow
      Transplant Registry (IBMTR) on bone marrow transplantation results in different
      phases of chronic granulocyte leukemia and prognostic model for survival of
      younger leukemic patients according to which there are three groups of patients.
      The mathematical method estimated cumulative risks of the final therapeutic
      results. This model has shown that the time limit for transplantation is the
      fourth year of the disease in the low risk group; the third year of the disease
      in the medium risk group and the second year in the high risk group of patients.

PMID- 9229679
TI  - [Hepatologic parameters in health personnel after several years of occupational
      exposure to anesthetic gases].
AB  - The aim of this study was to indicate necessity of establishing sensitive methods
      for early detection of hepatobiliary tract disorders after exposure of medical
      staff to anesthetic gases, as well as to follow-up working conditions in
      operating rooms. The examined group comprised the medical staff of the Surgical
      Department of the Institute of Surgery in Novi Sad. In the group of examinees
      levels of bilirubin in blood were increased; prevalent increase of the indirect
      bilirubin occurred too, while she increase of the direct bilirubin concentration
      was almost insignificant. Alanine aminotransferase concentration was slightly
      increased in the examined group, while aspartate aminotransferase reacted in much
      more expressed concentration increase. On the basis of gathered results it can be
      concluded that there are, for now, slight functional hepatic changes in the
      exposed workers, which may be the consequence of exposure to anesthetic gases.

PMID- 9229680
TI  - [Delivery with vacuum extraction--indications, technique and complications].
AB  - This study is a retrospective analysis of data on deliveries which ended up in
      vacuum extraction at the Clinic of Gynecology and Obstetrics in Novi Sad during
      two periods: 1983-85, and 1993-95. The aim of this study was to analyze
      indications, technique and complications of deliveries which ended up in vacuum
      extraction. Out of the total number of deliveries-17,110 in the period 1983-85,
      4.86% ended up in vacuum extraction. The perinatal morbidity was 10.82%, the
      perinatal mortality 15.13/1000. In the period 1993-95, there were 18,599
      deliveries, whereas 2.65% ended up in vacuum extraction. The perinatal morbidity
      was 8.93%, while perinatal mortality 11.12/1000. The risk of morbidity occurring
      in surgical procedures can be decreased if prompt vacuum extraction is performed.

PMID- 9229681
TI  - [Visceral protein status and hyperlipoproteinemia in patients on hemodialysis].
AB  - Long-term therapy and inadequate diet regimens in terminal phase patients with
      renal insufficiency lead to loss of body weight which causes changes in
      anthropometric indexes. The occurrence of hypoalbuminemia in chronic hemodialysis
      patients without nephrotic syndrome, is a clear sign of malnutrition. The aim of
      this study was to establish the visceral protein status in these patients as well
      as to find if there is a difference in this status in regard to hyperlipemic and
      normolipemic patients. 45 chronic dialysis patients were examined: 26 males with
      a mean age of 52.4 years and 19 females with a mean age of 51.3 years. They were
      divided into two groups: the first group of 22 hyperlipemic patients and the
      second group of 23 normolipemic patients. The control group consisted of 18
      healthy subjects (9 females with a mean age of 58.3 years and 9 males with a mean
      age of 55.7 years). In regard to lipid fractions we determined the total
      cholesterol, HDL (high density lipoprotein), LDL (low density lipoprotein)
      cholesterol and triglycerides. The following anthropometric indexes have been
      used: BMI (body mass index) and muscle mass index (triceps). Albuminemia was
      performed in all subjects as an indicator of undernutrition. There was a
      significant difference in albumin level in hyperlipemic and healthy subjects (p =
      0.0001), as well as normolipemic and healthy subjects (p = 0.0001), whereas no
      significant difference was established between hyperlipemic and normolipemic
      subjects. Values for triceps as a muscle mass index significantly differed in the
      group of normolipemic subjects (p = 0.03). Body mass index did not significantly
      differ among groups. In the group of normolipemic subjects BMI was significantly
      in correlation with values for triceps (p = 0.001). Significant correlation
      between albumin level and anthropometric indexes was not established. Gathered
      results indicate that in the group of normolipemic hemodialysis patients
      malnutrition can be dangerous.

PMID- 9229682
TI  - [Health and social problems in the aged].
AB  - This study reviews data from a poll conducted in three municipalities of
      Vojvodina on health and social problems of 60-year old and older people (n =
      104). Poverty and illness are the main two problems aged people have to deal
      with, whereas exhaustion, pains, moving around with difficulty, poor vision,
      heart and breathing problems, as well as cardiovascular diseases and diseases of
      the musculoskeletal system are the most frequent health problems. Socializing is
      poor in the old age. Every third aged person visits nobody, while every fifth
      aged person is visited by nobody. About 3% of examinees describe their
      relationships with children as negative. That is why it is necessary to organize
      a health care of the aged which should maintain health and functional abilities
      into the old age with adequate social care of both closed and open type as long
      as possible.

PMID- 9229683
TI  - [Arthroplasty in the treatment of congenital anomalies of the hip in adults].
AB  - At the Clinic for Orthopedic Surgery and Traumatology in Novi Sad, 79 adult
      patients with osteoarthritic hip dysplasia underwent total joint replacement
      surgery in the period 1984-1993. 45 patients were followed-up for an average time
      of 4.2 years. The results obtained have been evaluated following the criteria of
      Postel-Merle-d'Aubigne's hip rating system. After surgery 37 (82.2%) patients had
      minimal or no pain at all, while the hip flexion was over 75 degrees in 35
      (75.5%) patients. 9% of patients could not walk longer than 20 minutes with a
      flexion under 50 degrees. Firm footfall and slight limp in exhaustion occurred in
      35 (75.5%) patients, while 7 (15.5%) patients were extremely unstable and were
      able to get about on crutches. The gathered results confirm that total hip
      replacement in patients with osteoarthritic dysplastic hip improves stability and
      hip joint movement as well as pain reduction.

PMID- 9229684
TI  - [Perineal endometriosis at the site of an episiotomy scar].
AB  - This study presents a case of vaginoperineal histologically verified
      endometriosis at the site of episiotomy scar in a 40-year female subject, 17
      years after delivery. Apart from episiotomy during delivery manual revision of
      the uterus was performed and the cervical rupture managed. Residue symptoms
      occurs 8 months after the first surgical excision. Clinical data indicate that
      decidua implantation at the site of episiotomy occurred during the manual
      revision of the uterine cavity during delivery.

PMID- 9229685
TI  - [The lungs in human immunodeficiency virus type 1 infection].
AB  - This report describes a case of two patients who were admitted to the Zadar
      hospital and according to clinical symptoms directed to the Department of Lung
      Diseases. Both patients were temporarily employed abroad. It has been established
      that they were infected with human immunodeficiency virus type 1 (HIV-1). One of
      the patients has been moved to the Department of Infectious Diseases and later to
      Zagreb, while the other has returned abroad. On admission to the hospital of the
      Zadar Medical Center none of them answered the question about being engaged in
      risky behavior. In 1990 there were 699 registered patients hospitalized and 745
      registered in the protocol of the Outpatient Clinic of the Department of Lung
      Diseases. 0.069% of patients were HIV-1-infected. In 1991, there were 520
      hospitalized and 453 outpatients, whereas 0.102% were HIV-1-infected and
      registered subjects. It must be pointed out that these are only numbers of
      registration and not subjects, because there were patients who were examined or
      hospitalized twice or more times during the corresponding calendar year. The aim
      of this study was to point to a new differentially-diagnostic problem present
      especially at the Department of Lung Diseases after AIDS has become part of our
      reality. There still remains a problem in regard to detection of HIV-1
      seropositivity in patients at departments with opportunistic infections such as
      tuberculosis.

PMID- 9229686
TI  - [The first physicians in Banat. I].
AB  - The first part deals with first physicians in Novi Knezevac, Kikinda and
      Zrenjanin. The first physician in Novi Knezevac was Dr. Sima Matejin-the first
      phthisiologist, and since then 139 physicians have been employed there, for
      example: Dr. Prokap Tokin, Dr. Marija Popav-Radulovic, Dr. Karpa Svircev and
      present director Dr. Dusan Ristic. Kikinda or Great Kikinda has been recorded in
      1416, as a district of Kikinda (1774-1876). The first Serbian physician there was
      Dr. Georgije Paunic written about in 1778, and then Dr. Johan Reid, Dr. Ferenc
      Kriner, Dr. Jovan Petrovic from Temisvar, Dr. Jovan Tihi, Dr. Hranislav
      Mihajlovic, Dr. Vrtipraski Radovan, Dr. Jovan Valovic, Dr. Lipler, Dr. Jovan Pacu
      and others. The Great Beckerek, Petrovgrad or Zrenjanin was first mentioned as a
      village in 1326 and the first physicians we know about were Dr. Gandzan Joanis,
      Dr. Refranciskus, Dr. Roka Macas, Dr. Djordje Cokerljan from Melenci, Dr. Karolj
      Bobor from Elemir, Dr. Antonius Bah from Segedin, Dr. Aleksandar Velisavljevic,
      Dr. Misa Matic, brothers Kamenkovic and others.

PMID- 9229687
TI  - [Information technology in medicine].

PMID- 9229688
TI  - [The epithelium of the periodontal pocket--an electron microscopy analysis].
AB  - The aim of this study was to examine intra- and intercellular changes that
      characterize the periodontal pocket epithelian. Biopsy specimens of human gingiva
      were prepared for an electron microscope study by a routine histological
      procedure. Results of the histological preparations analyses revealed changes
      significant for pathogenesis of gingivitis and periodontal disease because they
      cause destruction of epithelial barrier. Such a damaged periodontal pocket
      epithelium enables further invasion of harmful noxae and spreading of destructive
      processes into deeper parts of the periodontium.

PMID- 9229689
TI  - [Acute rubella virus infection in women of reproductive age in Vojvodina 1994
      1995].
AB  - In order to establish rubella virus serologic status in 1034 women of
      reproductive age in Vojvodina during a two year period, 319 nonpregnant and 715
      pregnant women were examined. The aim of this study was to examine the frequency
      of occurrence of acute rubella virus infections in women of reproductive age; to
      establish levels of sensitivity to rubella virus, as well as the impact of
      pregnancy on values of titer antihemagglutinine (HI--hemagglution inhibition)
      antibodies. By determining immune status against rubella in women of reproductive
      age high risk groups can be established so that severe consequences of congenital
      rubella can be prevented. On the basis of titer values of the virus rubella HI
      antibodies in even samples of sera it has been established that 97.3% of women of
      reproductive age in Vojvodina in 1994-1995 are immune to rubella. In this period
      2.7% of women were established to be vulnerable to rubella virus infection. On
      the basis of established IgM antibodies acute rubella was detected in 0.31% of
      nonpregnant women. 26.85% of pregnant women made risky contacts considering whole
      period of pregnancy. In such circumstances the percentage of pregnant women with
      acute infection in Vojvodina during the period 1994-1995 is low and makes 0.28%.

PMID- 9229690
TI  - [Clinical use of granulocyte colony stimulating-factors (GM-CSF and G-CSF].
AB  - Humoral regulation of granulocytopoiesis was proven 30 years ago by discovery of
      factors which stimulate production of granulocyte colonies (CSF-colony
      stimulating factors), while clinical utilization of recombinant human colony
      stimulating factors (rhGM-CSF and rh-CSF) is present for the last 10 years. On
      the basis of this, today we have a lot of experience in regard to indications,
      modes and results of their clinical utilization. Clinical utilization of CSF is
      divided into three fields: treatment of the neutropenic syndrome, utilization in
      oncologic patients and in bone marrow transplantation. The best results have been
      achieved in neutropenic syndrome therapy, both chronic (congenital, cyclic and
      idiopathic neutropenia, aplastic anemia and myelodysplastic syndrome) and acute
      (granulocytopenia drug induced, postirradiation neutropenia). In oncologic
      patients it is used to eliminate neutropenia which occurs after cytostatic
      therapy with standard doses or high dose cytostatic therapy with better effects
      on the tumor, but with myeloablation. Granulocyte colony-stimulating factor is
      also used for stimulating fast granulocytopoiesis in autologous or allogeneic
      bone marrow transplantation, in unsatisfactory transplants especially. In recent
      years it has been used for mobilization of progenitor CD34+ cells in the donor in
      order to perform their transplantation, especially in treatment of chronic
      myeloid leukemia. At our institution G-CSF has been successfully used in 17
      patients.

PMID- 9229691
TI  - [Opioid drugs in neonatal anesthesia].
AB  - This study deals with utilization of opioid drugs in newborns during anesthesia
      as well as pain management in the postoperative course. It is based on the
      author's 20-year experience in neonatal anesthesia.

PMID- 9229692
TI  - Destruction of the nasal septum by aspergillus infection after autologous bone
      marrow transplantation.

PMID- 9229693
TI  - Hepatitis G infection.

PMID- 9229694
TI  - Hepatitis G infection.

PMID- 9229695
TI  - A comparison of coronary-artery stenting with angioplasty.

PMID- 9229696
TI  - Disorders of the autonomic nervous system.

PMID- 9229697
TI  - Idiopathic biliary ductopenia.

PMID- 9229698
TI  - Delayed severe hypertriglyceridemia from tamoxifen.

PMID- 9229699
TI  - Ratio of specialists to family practitioners in the United States.

PMID- 9229700
TI  - Consent for clinical research.

PMID- 9229701
TI  - Subpoenas and science.

PMID- 9229702
TI  - Subpoenas and science.

PMID- 9229704
TI  - How to win the New York state lottery... Without buying a ticket.

PMID- 9229703
TI  - Problems of Drug Dependence 1996: Proceedings of the 58th annual scientific
      meeting.

PMID- 9229705
TI  - European Society for Paediatric Haematology and Immunology. 16th annual meeting.
      May 14-17, 1997, Thessaloniki, Greece. Abstracts.

PMID- 9229706
TI  - Alternative routes of drug administration--advantages and disadvantages (subject
      review). American Academy of Pediatrics. Committee on Drugs.

PMID- 9229707
TI  - Health care for children of immigrant families. American Academy of Pediatrics.
      Committee on Community Health Services.

PMID- 9229708
TI  - Ceftriaxone for acute otitis media.

PMID- 9229709
TI  - Ceftriaxone for acute otitis media.

PMID- 9229710
TI  - Potential fluoxetine chloride (Prozac) toxicity in a newborn.

PMID- 9229711
TI  - Varicella exposure at a summer pulmonary camp.

PMID- 9229712
TI  - Martin Couney's story revisited. The AAP Perinatal Section Ad Hoc Committee on
      Perinatal History.

PMID- 9229713
TI  - Cost-effectiveness of RespiGam at a university teaching hospital.

PMID- 9229714
TI  - Preventing childhood lead poisoning: screening practices in the United States.

PMID- 9229716
TI  - [Measures to take after exposure to blood].

PMID- 9229715
TI  - The use of synthetic dyes for identification of the amniotic sacs in multiple
      pregnancies.

PMID- 9229717
TI  - [Fast thin-layer densitometric determination of the nootropic piracetam in
      biological material].
AB  - After oral doses of piracetam this drug is detectable in serum as well as in
      urine after formation of the red Fe(III)-hydroxamatecomplex by thin-layer
      densitometry. Detection in serum requires extraction with a mixture of
      dichloromethane/ methanol, while urine can be used directly after dilution. The
      limit of quantification in urine is 100 micrograms/ml and in serum 4.0
      micrograms/ml. The new method was validated by HPLC. The coefficient of
      correlation was 0.9999% for determination in urine and 0.9986% for determination
      in serum.

PMID- 9229718
TI  - [The photostability of antimycotics. 3. Photostability of locally acting
      antimycotics].
AB  - The photochemical stability of a number of topical antimycotic drugs was tested.
      The light sensitivity decreases in the order naftifine, sulbentine, cloxiquin,
      tolnaftate and chlorphenesin. A liquid chromatography-mass spectrometry system
      was used to identify a number of photodegradation products. Light exposure of
      sulbentine leads to the formation of benzylisothiocyanate. Chlorphenesine
      solutions undergo photodehalogenation with the formation of varying
      photodegradation products depending on the solvent used. The photochemical
      reactions of naftifine are a cis-trans-isomerization and the formation of a dimer
      product. Drug preparations are also degraded under light exposure in a simulated
      topical application. Excipients in the drug preparations strongly influence the
      photodegradation kinetics and the chemical structure of photodegradation
      products.

PMID- 9229719
TI  - [Isolation and receptor binding properties of alkaloids and lignans from
      Valeriana officialis L].
AB  - In addition to the known Valeriana-Meanalkaloid, four 7,9':7'9-Diepoxylignans
      were isolated from the roots of Valeriana officinalis L. They were tested in
      different radioreceptorassays at the 5-HT1A-, GABAA-, benzodiazepin and mu-opiate
      receptor.

PMID- 9229720
TI  - [Equipment and stocks in a German hospital pharmacy in the 19th century].
AB  - Two inventories from the hospital pharmacy in Cologne, founded 1807, give insight
      into the equipment of such an institution in Germany during the nineteenth
      century. The lists dated 1818 and 1884 have been transcribed and are presented
      verbatim. Additionally, a stock list dated 1817 was investigated.

PMID- 9229721
TI  - [Effect of culture conditions on the production of cellulases by Trametes
      trogii].
AB  - Production of the components of the cellulase complex by Trametes trogii was
      investigated under different culture conditions. Endoglucanase, exoglucanase and
      beta-glucosidase were produced by Trametes trogii under shaken and stationary
      conditions using crystalline cellulose as the only carbon source. No marked
      differences were found for endo- and exoglucanase production between both culture
      conditions. In shaken cultures beta-glucosidase values doubled those obtained in
      stationary conditions. All maxima were reached approximately 10 days earlier in
      static cultures than in shaken ones. The addition of glucose to the culture
      medium improved growth but decreased abruptly the enzyme production. The optimal
      pH of the medium for the synthesis of the enzymes was 5.6, and the best
      incubation temperature was 25-28 degrees C. Enzyme activities were maximal at pH
      3.1 and 45 degrees C (endoglucanase), pH 4.1 and 50 degrees C (exoglucanase) and
      pH 5.3 and 60 degrees C (beta-glucosidase).

PMID- 9229722
TI  - [Inoculation of chickpeas with Rhizobium sp. native to the province of Cordoba,
      Argentina].
AB  - Native strains of Rhizobium were selected from a chickpea growing area with the
      purpose of producing inoculants tolerant to environmental conditions of the
      province of Cordoba. The strains were selected for nitrogen fixing capacity and
      specificity with four plant genotypes using the following parameters: number of
      nodules, plant biomass and nitrogen content. Native population of Rhizobium spp
      in the province of Cordoba showed better competition ability than foreign strains
      with similar response to different plant genotypes.

PMID- 9229723
TI  - [Combined activity of meliacin and foscarnet against different strains of herpes
      simplex virus type 1 using a three-dimensional model].
AB  - We evaluated the in vitro antiviral activity of meliacin combined with foscarnet
      on the herpes simplex type 1 (HSV-1) strains F and B2006 (tk-) replication. The
      effective concentrations for 50% inhibition of HSV-1 (F) were 12.5 micrograms/ml
      for meliacin and 15.7 micrograms/ml for foscarnet, while for HSV-1 (B2006) were
      3.1 micrograms/ml and 126 micrograms/ml, respectively. The data were analyzed for
      quantitation of synergism, additivity, and antagonism of multiple drug effect by
      the three-dimensional model. Some of the meliacin -foscarnet combinations
      synergistically inhibited HSV-1 (F) and HSV-1 (B2006) replication in vitro at
      concentrations that did not reduce cellular viability.

PMID- 9229724
TI  - [Seroprevalence of viral infections in llamas (Lama glama) in the Republic of
      Argentina].
AB  - This study reports the seroprevalence of bovine viral infections in llamas (Lama
      glama) in Argentina. This is the first study made in the country including 390
      llamas and testing antibodies against eight viruses. Samples were collected from
      nine farms distributed in three different provinces: Buenos Aires, Cordoba and
      Jujuy. The samples were tested for antibodies against eight viruses known to
      infect cattle: bovine herpesvirus type 1 (BHV-1), bovine viral diarrhea virus
      (BVDV), bovine adenovirus type 3 (BAdV III), bovine enterovirus (BEV), bovine
      rotavirus (BRV), bluetongue virus (BTV), bovine leukemia virus (BLV), and foot
      and-mouth disease virus (FMDV). The antibody prevalences detected in llamas were:
      BHV-1 in 0.7% of the samples (3/390), BVDV in 2.0% (8/390), BAdV III in 5.1%
      (20/390), BEV in 4.6% (18/390), BRV in 87.6% (342/390). No antibodies were
      detected against BTV, BLV and VIAA (viral infection associated antigen) in any of
      the analyzed camelids.

PMID- 9229725
TI  - [Bovine diarrhea virus: an update].
AB  - Bovine Viral Diarrhea Virus (BVDV) is a pathogen of cattle, member of the family
      Flaviviridae, genus pestivirus, which also includes Classical Swine Fever Virus
      (CSFV, or hog cholera virus), and Border Disease Virus of sheep (BDV). It causes
      important economical losses associated mainly with reproductive failure.
      Pestiviruses are small enveloped viruses, with a diameter of about 40 nm. The
      nucleocapsid is probably icosahedral . The genome consists of a single stranded
      positive RNA, encoding approximately 430 kD of proteic product. Genetic
      expression consists of the synthesis of a polyprotein which is co- and post
      translationally processed. According to its behavior "in vitro" two biotypes can
      be distinguished: non cytopathic (ncp) and cytopathic (cp), most probably derived
      from the ncp through mutations and/or recombination. BVDV is able to cross the
      placenta and infect the fetus, causing a variety of problems, from fetal death to
      the birth of a persistently infected (P) calf, according to the fetal age at the
      time of infection. PI animals are immunotolerant to the virus and shed it in all
      secretions. Only the ncp biotype has been isolated from PI animals. The
      superinfection of a PI animal with a cp strain causes mucosal disease, always
      fatal. Outbreaks of a severe, sometimes hemorrhagic disease, caused by ncp BVDV,
      have occurred in Canada and USA since 1993. Genomic and serological differences
      between the "traditional" strains and the viruses isolated from these outbreaks
      led to the division of BVDV in subtypes I and II, both including cp and ncp
      strains. Analyses of the non coding 5'-UTR zone of the genome of pestiviruses
      from different species (bovine, ovine, porcine) suggest that there are at least 3
      genotypes within the genus. A new classification of these viruses, based on
      genomic sequence instead of species of origin, has been proposed. Genomic
      heterogeneity exists in the BVDV genome, which presents 3 hypervariable zones, 2
      of them in the major neutralizing protein. In Argentina prevalence of BVDV
      antibodies in cattle population is 70%, and the prevalence of persistent
      infections is around 1%.

PMID- 9229727
TI  - [Methods of bioimaging and their principles].

PMID- 9229726
TI  - [Yeast infections: causative agents and their antifungal resistance in
      hospitalized pediatric patients and HIV-positive adults].
AB  - Candidiasis has increased its frequency over the last decade, particularly among
      hospitalized patients where it is accompanied with high rates of mortality, and
      in patients with AIDS who are predisposed to oropharyngeal or esophageal
      candidiasis. The aim of this study was to determine the frequency of appearance
      of different yeast species and the resistance profile to current antifungal drugs
      in hospitalized pediatric patients and adult HIV patients from 5 institutions of
      Buenos Aires City and suburbs, and La Plata City, during the period 1993-1995, in
      order to obtain local and updated information. Candida albicans was the etiologic
      agent recovered in 87% of the 214 HIV positive patients with oropharyngeal
      candidosis, and in 50% of the 209 hospitalized pediatric patients. In the latter
      group 28% of these infections were due to Candida parapsilosis and 18% to Candida
      tropicalis, but only 2% and 4% of oral candidosis were caused by these organisms.
      Detection of Malassezia furfur and Hansenula anomala, responsible of systemic
      infections, and Trichosporon beigelii, isolated from a burn patient, were
      considered remarkable since these organisms appear to be emerging pathogens.
      Azole resistant species as Candida krusei and C. glabrata were mostly recovered
      from HIV positive patients, exposed to fluconazole treatment. A very low number
      of amfotericin B "resistant" yeasts (n = 9) were observed in both groups.
      However, resistance to azole drugs, particularly to fluconazole, was found in
      pediatric patients (13%) and in HIV infected adults (34%).

PMID- 9229728
TI  - [The need for alfentanyl in total intravenous anesthesia. Comparison between
      laparoscopic cholecystectomy and subcostal laparotomy].
AB  - OBJECTIVE: To quantify intraoperative consumption of alfentanil in
      cholecystectomy by laparoscopy or by the traditional approach; to evaluate its
      relation to time until extubation, presence and intensity of postoperative pain
      and vomiting. PATIENTS AND METHODS: Prospective, non randomized study. Forty
      female physical status ASA I-II patients between 18 and 60 years of age scheduled
      to undergo subcostal cholecystectomy by subcostal laparotomy (group CSL, n = 20)
      or by laparoscopy (group CL, n = 20). Total intravenous anesthesia with propofol,
      alfentanil and atracurium was provided. A continuous infusion of alfentamil 1
      microgram/kg/min was used, with a supplement of 7 micrograms/kg when mean
      arterial pressure (MAP) rose more than 10% above baseline or with a supplement of
      14 micrograms/kg when MAP rose 20% or more above baseline. Variables measured
      were intraoperative alfentanil requirements, time until extubation, presence and
      intensity of pain in the immediate postoperative period and incidence of
      vomiting. RESULTS: Alfentanil consumption was 1.81 and 1.63 micrograms/kg/min and
      time to extubation was 17.5 and 14.05 min in the CL and CSL groups (p < 0.05),
      respectively. There was less pain in the early postoperative period in the CL
      group (36.8% for the CL patients as opposed to 85% in the CSL group, p < 0.01)
      and pain was less intense (p < 0.01). The incidence of vomiting was 42.1% in
      group CL and 25% in group CSL (p = NS). CONCLUSIONS: Insufflating the
      pneumoperitoneum for laparoscopic surgery brings about hemodynamic changes that
      increase intraoperative consumption of alfentanil during surgery, and this can
      lead to delayed awakening.

PMID- 9229729
TI  - [Low-flow anesthetic systems. Closed circuit].

PMID- 9229730
TI  - [The Internet web in anesthesiology-recovery].
AB  - The impact the growing body of information accessible by Internet may have on
      anesthesiology and intensive care recovery departments is described. A brief
      overview of the philosophy, content, characteristics and functioning of Internet
      communication is given, including how to gain access and what access may mean for
      a department or for an individual anesthesiologist's training. Finally, the main
      resources available on the Internet are listed.

PMID- 9229731
TI  - [Angiographic control of postpartum obstetrical hemorrhage. A clinical case and
      review of the literature].

PMID- 9229732
TI  - [Acquired neuromyotonia (Isaacs' syndrome): clinical characteristics and
      anesthesia implications].

PMID- 9229734
TI  - [Anesthesia in a patient with Klippel-Trenaunay-Weber syndrome].

PMID- 9229733
TI  - [Gas embolism secondary to intraoperative use of hydrogen peroxide].
AB  - Hydrogen peroxide solution (H2O2) is used to irrigate and clean wounds. When
      applied to tissue hydrogen peroxide decomposes rapidly as a result of the action
      of catalases, releasing oxygen in the process. High pressure irrigation of the
      washing of closed cavities can cause serious complications. We report a case of
      gas embolism arising from the use of hydrogen peroxide during surgery for
      hydatidosis of the liver. A 64-year-old woman underwent surgery for removal of a
      hydatid cyst of the liver. When pressurized injection of 10 ml of 3% hydrogen
      peroxide was applied to the cystic cavity, cardiac arrhythmias were observed, a
      long with decreased PetCO2, hypotension and a "water mill" heart murmur. Gas
      embolism was suspected and treatment was instated immediately. Clinical course
      was good and without complications. We wish to warn against the potential dangers
      of using peroxide during surgery and of the importance of capnography for early
      diagnosis of gas embolism.

PMID- 9229735
TI  - [Anesthesia implications in Klippel-Trenaunay syndrome].

PMID- 9229736
TI  - [Anesthesia for cesarean section in patients with mitral valve prolapse].

PMID- 9229737
TI  - [Apnea and retarded awakening following oral premedication with midazolam].

PMID- 9229739
TI  - [Anesthesiology and Internet].

PMID- 9229738
TI  - [Thoracic epidural anesthesia combined with general anesthesia with propofol for
      thymectomy in myasthenia gravis].

PMID- 9229740
TI  - [Relationship between laryngoscopy degree and intubation difficulty].
AB  - OBJECTIVES: To determine the relation between difficult intubation and grade of
      direct laryngoscopy, as well as the factors that influence them, and prognosis.
      PATIENTS AND METHOD: In 1,336 patients receiving general anesthesia, seven airway
      measurements were made to reflect degree of difficulty and predictive value of
      presurgical tests on direct laryngoscopy and intubation. RESULTS: The incidences
      of difficult laryngoscopic and intubation procedures were 1.4 and 3.0%,
      respectively. Difficult intubation was more frequent in women and in patients
      between 40 and 65 years of age (p < 0.05). In 105 intubations (64.8%) performed
      with moderate difficulty (use of a stylette, external laryngeal pressure or two
      tries) and 17 (41.5%) performed with difficulty (three or more tries), the
      laryngoscopic procedure was graded as easy (Cormack-Lehane grade I-II). In these
      cases (easy laryngoscopy with moderate/difficult intubation), the causes recorded
      were size of endotracheal tube in comparison with the laryngeal opening (n = 11);
      anterior glotis (n = 36); insufficient relaxation (n = 31); disease in or beyond
      the vocal cords (n = 29); or undetermined (n = 15). In the easy intubation cases,
      the laryngoscopic procedures were grade III in 2.9%. Intubation was difficult in
      16.3% (n = 39) of patients presenting some type of abnormality upon examination
      of the airway (p < 0.05). The airway characteristic that best predicted
      laryngoscopic difficulty was extension of the lower neck to 90 degrees (relative
      risk of 4.46), mouth opening less than 3.5 cm (3.92), presence of two airway
      abnormalities (4.25) and presence of three or more abnormalities (5.39) (p <
      0.01). CONCLUSION: The fact that cases of easy laryngoscopy coincide with
      difficult intubation suggests that, to the degree of intubation difficulty must
      be added extrinsic factors (individual skill, maneuvers performed,
      instrumentation, relaxation of the laryngeal musculature and others) that are
      hard to standardize and reflect when predicting an intubation by the grade of
      difficulty in laryngoscopy.

PMID- 9229741
TI  - [Total intravenous anesthesia with propofol in orthotopic liver transplantation
      in swine].
AB  - OBJECTIVE: To study the use of total intravenous anesthesia with propofol as an
      anesthetic model for orthotopic liver transplantation (OLT) in pigs. ANIMALS AND
      METHOD: Fifteen OLT were performed in pigs using portacava-jugular veno-venous
      shunt with an injector pump. Anesthesia was maintained by perfusion of 10 mg/kg/h
      propofol. Hemodynamic and biochemical measurements were recorded at the following
      times: AO, baseline; AI, five minutes before removal of the liver; B1, five
      minutes later but before starting the bypass injector pump; B2, five minutes
      after starting the injector pump; B3, five minutes before reperfusion; C1, five
      minutes after starting reperfusion, and C2, after aortic declamping. RESULTS: No
      cases of malignant hyperthermia appeared. When the liver was removed cardiac
      output decreased (p < 0.01), as did mean arterial pressure (p < 0.01), mixed
      venous saturation (p < 0.05), pulmonary capillary pressure and temperature (p <
      0.05). Pulmonary vascular resistances increased (p < 0.05). CONCLUSIONS: The use
      of total intravenous anesthesia with propofol is a satisfactory experimental
      anesthetic model for OLT in pigs, and it prevents the possible appearance of
      malignant hyperthermia.

PMID- 9229742
TI  - [Value of tumor markers for screening and diagnosis (except prognostic and
      surveillance values) in primary bronchial cancers].

PMID- 9229743
TI  - [Value of serial tumor markers for determining the prognosis and predicting
      treatment response and survival].

PMID- 9229744
TI  - [Value of tumor markers in surveillance of primary bronchial cancers and to
      evaluate therapy].

PMID- 9229745
TI  - [Value of serial tumor markers for the detection of recurrences].

PMID- 9229746
TI  - [Carcinoembryonic antigen].

PMID- 9229747
TI  - [CYFRA 21-1].

PMID- 9229748
TI  - [Neuron specific enolase].

PMID- 9229749
TI  - [Recommendations concerning the use of serial tumor markers in management of
      primary bronchial cancers. Society of French Pneumology. Synthesis and
      recommendations].

PMID- 9229750
TI  - [Which tumor markers should be used in primary bronchial cancers?].

PMID- 9229751
TI  - [Chronology of portal hypertension, decreased sodium excretion, and activation of
      the renin-angiotensin system in experimental biliary cirrhosis].
AB  - OBJECTIVES: 1) To evaluate the biochemical, renal, histological and splanchnic
      and systemic hemodynamic abnormalities induced by bile duct obstruction in rats,
      and 2) to study the temporal relationships between the start of portal
      hypertension, decrease of urinary sodium excretion and activation of the renin
      angiotensin system. METHODS: Bile duct obstruction was induced in 127 male Wistar
      rats, and renal function, hemodynamic, biochemical and liver histology were
      evaluated at weeks 1, 2, 3 and 4 after complete bile duct obstruction; the data
      were compared to that in 30 control rats. RESULTS: Portal pressure significantly
      increased at week 1 (11.7 +/- 1.5. vs. 7.8 +/- 1.5 mmHg, p < 0.05) while the mean
      arterial pressure remained stable until week 4 when a slight decrease was
      observed (91.3 +/- 6.6 vs. 96.1 +/- 8.6 mmHg in control rats). A significant
      decrease in urinary sodium excretion was observed at week 1 (1.1 +/- 0.5 mEq/24
      h) compared to control rats (2.3 +/- 0.6 mEq/24 h). In addition, hyperreninemia
      was observed at week 1 (5.1 +/- 0.2 vs. 2.4 +/- 1.3 ng Ang l/mL/h, p < 0.05) and
      hyperaldosteronism at week 2 (103 +/- 46 vs. 25.1 +/- 8.8 ng/24 h, p < 0.05)
      compared to control rats. CONCLUSION: A temporal relationship between the
      beginning of portal hypertension and a decrease of renal sodium excretion,
      hyperreninemia and hyperaldosteronism was observed in bile duct ligated rats.
      This experimental model could be used to evaluate the effects of new drugs to
      prevent biliary cirrhosis including the abnormalities in the renal handling of
      sodium.

PMID- 9229752
TI  - [Endocrine tumors of the pancreas at a Mexican institution].
AB  - OBJECTIVE: To analyze characteristics of patients with endocrine tumors of the
      pancreas seen between 1960 and 1992 at the Instituto Nacional de la Nutricion.
      MATERIAL & METHODS: The clinical records of 38 patients with endocrine tumors of
      the pancreas were reviewed. Overall characteristics, diagnostic studies,
      intraoperative findings, treatment and outcome were analyzed. The archival
      histological specimens were revised and immunohistochemical stainings were
      performed in the non-functioning tumors. RESULTS: Twenty patients had
      hyperinsulinism, 10 non-functioning tumors, and eight a Zollinger-Ellison
      syndrome. The mean age of patients with hyperinsulinism was 38 years (8 males and
      12 females); 18 were sporadic and two associated with MEN I syndrome. In 16
      patients an insulinoma was removed: (6 in the head, 5 in the body, 5 in the tail
      of the pancreas). A cure was documented in 14 patients with sporadic tumors but
      not in the two cases associated with MEN I; 15 tumors were benign. Three patients
      with the Zollinger-Ellison syndrome were males and five females with a mean age
      of 41 years. Seven tumors were sporadic and one associated with the MEN I
      syndrome; 70% were located in the gastrinoma triangle. Local excision was
      performed in five and gastrectomy in three. The cure rate was 60% and malignancy
      was documented in 40%. Two males and eight females with a mean age of 30 years
      had non-functioning tumors (9 sporadic and one associated to MEN I). There was a
      positive immunohistochemistry in 60% of the tumors; 90% were malignant and the
      cure rate was 10%. CONCLUSIONS: Insulinoma is the most common endocrine tumor of
      the pancreas in our hospital. The cure rate for insulinomas, gastrinomas and non
      functioning tumors was 90%, 60% and 10% and malignancy was documented in 5%, 40%
      and 90% respectively.

PMID- 9229753
TI  - Immunophenotypic characteristics of the blast crisis in chronic myeloid leukemia.
AB  - OBJECTIVE: To characterize the immunophenotype of blast crisis (BC) in Mexican
      patients with chronic myeloid leukemia (CML). MATERIAL AND METHODS: Mononuclear
      cells of 17 patients with CML in BC were immunophenotyped employing a panel of 18
      monoclonal antibodies: CD5, CD10, CD14, CD22, and anti-HLA-DR used in all
      patients; CD2, CD15, CD19, CD34, and CD41 in 13 to 16 patients; and CD3, CD7,
      CD13, CD20, CD21, CD33, CD42b, and CD61 in less than 10 patients. RESULTS:
      Myeloid was the most frequent type (9/17 cases) followed by lymphoid (6/17) and
      hybrid or mixed lineage (2/17). Four of the myeloid BC expressed
      megakaryocyte/platelet associated antigens; 5 of 6 cases with lymphoid BC showed
      an early precursor B cell immunophenotype (HLA-DR+, CD10+), and the other was an
      uncommon case of lymphoid B/T transformation (CD19+, CD5+). The CD34 antigen was
      present in 6 out of 15 cases: 4 patients with lymphoid BC, 1 with myeloid
      transformation, and 1 with megakaryoblastic BC. CONCLUSIONS: Our findings are
      comparable to those found in the literature comprising 192 patients. The present
      study confirms the lineage heterogeneity of CML BC and suggests that extensive
      immunophenotyping may allow insight for a more precise recognition of normal and
      leukemic ontogenesis.

PMID- 9229754
TI  - [Two cases of heterologous transplantation with peripheral blood].
AB  - The first two cases in Mexico of patients with hematological malignancies treated
      with heterologous peripheral blood stem cell transplantation are presented. The
      stem cells were mobilized in the siblings by means of filgrastim; in one case,
      the graft was obtained from an identical twin and in the other from an HLA
      identical sibling. In both instances the post-transplant aplasia lasted less than
      15 years and the engraftment was complete. In the allogeneic transplantation, the
      graft versus host disease was treated with immunosuppression. The approximate
      cost of each of these procedures was 20000 U.S. dollars. The advantages of
      grafting heterologous peripheral blood stem cells instead of bone marrow cells
      are briefly discussed, focusing on economic aspects.

PMID- 9229755
TI  - [A case of autoimmune thrombocytopenic purpura and dengue].
AB  - Dengue fever was detected in Yucatan in 1979. Since then, about 17,000 clinical
      cases have been reported, of which 1169 were confirmed by the presence of
      specific antibodies (IgM and IgG) and/or virologic studies; 10 of the cases were
      classified as dengue haemorrhagic fever and four died. The disease is endemic in
      the region and serotypes 1, 2 and 4 have been observed. This paper describes a
      patient with chronic autoimmune thrombocytopenic purpura who developed a primary
      dengue infection with hemorrhagic manifestations and responded to
      corticosteroids. We discuss the physiopathogeny of thrombocytopenia and analyze
      the utility of treatment with corticosteroids in patients with autoimmune
      disease.

PMID- 9229756
TI  - [Seroprevalence of various viruses and sociodemographic characteristics of women
      seeking HIV screening].
AB  - OBJECTIVES: To study the seroprevalence of syphilis, herpes simplex-2, hepatitis
      B and HIV, and main sociodemographic characteristics and sexual behavior in women
      seeking testing for human immunodeficiency virus (HIV) in Mexico City.
      METHODOLOGY: A self-applied questionnaire was used in 454 women; and a blood
      sample was taken for the detection of markers for syphilis, herpes simplex virus
      2 (HSV-2)), antibodies against core and surface antigens for hepatitis B virus
      (HBV), and ELISA and Western blot for HIV. RESULTS: Seroprevalences for
      antibodies against T. pallidum, HSV-2, HBV and HIV were 4.6%, 29.3%, 3.5% and
      4.0%, respectively. Forty-six percent of the women were 20 to 29 years old; 70%
      reported complete junior high school or higher education level; 75% were sexually
      active; 56% reported at least one stable male sexual partner, 17% reported at
      least one occasional male sexual partner in the last three months, and 60% had
      had at least one sexual relation in the last three months; of these, only 18% (n
      = 82) reported the use of a condom as a preventive measure. Almost 30% of the HIV
      positive women had a history of blood transfusion, while less than 10% of the HIV
      negative women had received a transfusion. In addition, 10.6% said that one of
      their sexual partners was infected with HIV or had AIDS. CONCLUSIONS: Risks of
      HIV/STD transmission for this group of self-selected women were linked to blood
      transfusion, low education and, most important, the risk from male sexual
      partners who were HIV seropositive. It is expected that these results will
      contribute to the improvement and development of strategies for the control and
      prevention of STD among this population group, as well as the general population
      in Mexico.

PMID- 9229757
TI  - [Changes in blood coagulation in HIV infection].
AB  - The human immunodeficiency virus (HIV) infection is becoming more complex.
      Hemostatic abnormalities occur frequently in the patient with HIV. HIV-related
      thrombocytopenia (Tr-HIV) is the most common hemostatic disorder with a high
      morbidity and affects patients from every risk group independently of age, sex,
      or stage of infection. Two mechanisms are responsible for the Tr-HIV: bone marrow
      failure and immunological disorders, namely, circulating immune complex deposited
      on the platelet membrane and the production of autoantibodies directed against
      platelets. The treatment of choice is zidovudine; other available options are not
      as effective as zidovudine. In addition, there are some abnormalities in the
      fluid phase of the coagulation cascade which can produce bleeding or thrombosis
      in the HIV patient. The most common are a prolonged partially activated
      thromboplastin time test, the production of a lupic anticoagulant and
      anticardiolipin antibodies, and several abnormalities in the natural-occurring
      anticoagulants. The thrombotic thrombocytopenic purpura recently associated with
      HIV has a clinical presentation and treatment alternatives that closely resemble
      those for the classical disease. The knowledge of these hemostatic abnormalities
      in the HIV seropositive patient allows a more rational care of these patients.

PMID- 9229758
TI  - [When should a disease be diagnosed early and whose disease?].
AB  - Screening programs may seem useful and effective. However, in many cases the
      benefit is not clear and may actually do more harm than good. Each time a
      clinician asks for an early diagnostic test, the scientific evidence and the
      attributed risks need to be defined. The effectiveness of any early diagnosis
      test relies on the characteristics of the test itself, the disease to be ruled
      out, and the side effects of the test. Such effects may be physical and emotional
      and the outcomes may be against the well being of the patient. In general, if an
      early diagnostic test does not lead to improvement in the survival and/or
      morbidity of patients, its utilization is not justified.

PMID- 9229759
TI  - [Molecular biology in medicine. VII. Molecular hybridization].

PMID- 9229760
TI  - [Relations between physicians and the pharmaceutical industry].

PMID- 9229761
TI  - Proposed air pollutant standards.

PMID- 9229762
TI  - When should fatherhood stop?

PMID- 9229763
TI  - Drug development.

PMID- 9229764
TI  - Endosomal targeting and the cytoplasmic tail of membrane immunoglobulin.

PMID- 9229766
TI  - Magnetic field-cancer link: will it rest in peace?

PMID- 9229765
TI  - The mouse that prompted a roar.

PMID- 9229767
TI  - New lesion found in diseased brains.

PMID- 9229768
TI  - The daunting challenge of keeping HIV suppressed.

PMID- 9229769
TI  - Recovering from the ravages HIV.

PMID- 9229770
TI  - Developing a new view of evolution.

PMID- 9229771
TI  - Growing pains: evo-devo researchers straddle cultures.

PMID- 9229772
TI  - Signaling vascular morphogenesis and maintenance.

PMID- 9229774
TI  - [Magic of the impact factor--degeneration of a phenomenon].

PMID- 9229773
TI  - Which came first, the hypha or the yeast?

PMID- 9229775
TI  - [Elbow injuries in childhood].
AB  - Fractures and dislocations of the elbow are some of the most common injuries in
      childhood and adolescence. The majority occur in sport and play activities, e.g.,
      a fall from gymnastics apparatus or a bike, or from popular sports items, such as
      skateboards or in-line skates. The injuries can be divided into pure dislocations
      of the joint and fractures of the distal humerus, proximal radius and ulna, or
      combinations of both. In addition, extra- and intraarticular fracture types are
      defined, with the latter as partial or complete joint lesions. Dislocations of
      the elbow joint or the radial head can occur as single injuries or in combination
      with a fracture. Supracondylar fractures and avulsion fractures of the medial
      epicondyle are the most frequent extraarticular lesions of the distal humerus.
      Fractures of the lateral condyle prevail is incomplete intraarticular lesions. In
      the forearm, radial head and neck fractures are predominant while typical and
      atypical Monteggia injuries have a special status. The complex joint construction
      and the age-dependent appearance of the epiphyseal ossification centers sometimes
      make a correct radiological diagnosis difficult. The trauma history and an exact,
      clinical examination help to verify the injury, as do comparative X-ray studies
      of the uninjured side when necessary (but not routinely). Unlike other anatomical
      areas, most elbow injuries-even in the growing skeleton-are treated operatively.
      Hereby, the growth plates have to be respected using minimal amounts of small
      implants. Additional immobilization in a cast for 2-4 weeks is necessary in most
      cases but does not lead to a functional deficit-in contrast to adults. The
      implants should be removed as early as possible. Despite all therapeutic efforts,
      a significant number of late sequelae, such as malunions and functional
      impairment, can be seen. The rate of long-term complications increases in cases
      of untreated displacement of fragments or joint instability. Corrective measures
      are performed only in selected cases and after the growth plates are closed. Our
      own treatment regime is demonstrated using exemplary clinical cases of the
      different injuries and the results of a long-term follow-up study on sports
      injuries of the elbow in children. Errors in diagnosis and therapy, as well as
      possible complications, are pointed out.

PMID- 9229776
TI  - [Bone lengthening osteotomy in malunited clavicular fracture].
AB  - Most fractures of the clavicle heal well with nonoperative treatment. On rare
      occasions, malunited clavicular fractures are associated with a pattern of
      disability that includes not only pain but also functional or neurovascular
      impairment. In these cases, clavicular osteotomy and correction of the deformity
      should be considered. In four patients with a malunited fracture of the clavicle
      following nonoperative treatment, we performed a clavicular osteotomy for
      deformity. In all four patients the clavicular fracture healed with shortening
      associated with pain and ipsilateral glenohumeral dysfunction. The deformity was
      not associated with neurovascular dysfunction. In preoperative X-ray studies, the
      shortening of the malunited clavicle was between 0.9 and 2.2 cm in comparison to
      the contralateral clavicle. All patients underwent an extension osteotomy of the
      clavicle with interposition of an autogenous iliac crest bone graft. The follow
      up was 1-4 years postoperatively. The functional outcome was evaluated using the
      Constant-Murley and the UCLA score. All patients had immediate pain relief
      following osteotomy and correction of the deformity. The shoulder function
      rapidly improved, and the functional outcome was good in three out of the four
      patients. If there is associated functional impairment in malunited clavicular
      fractures, extension osteotomy combined with autogenous bone grafting may produce
      predictably good results.

PMID- 9229777
TI  - [Mid-term outcome after surgically managed re-rupture of the anterior cruciate
      ligament].
AB  - This retrospective study shows the results in 30 patients of revision surgery on
      their reruptured ACL. The follow-up time was 30 months on average (range 10-54
      months). The follow-up examination included subjective (Lysholm score, Tegner
      activity level rating score), clinical and radiological criteria and also
      instrumental laxity testing with the KT-1000 arthrometer. The overall evaluation
      was done according to the IKDC score. The follow up showed subjective and
      objective results almost equal to those after primary surgery on ACL. The IKDC
      score revealed certain abnormal and highly abnormal results, which demonstrated
      that revision ACL surgery gives poorer results than primary surgery.
      Nevertheless, we recommend reconstruction of a torn ACL even in a revision case
      to restore the knee function and prevent further menisceal and chondral damage
      and degeneration.

PMID- 9229778
TI  - [Manual ultrasound of the knee joint. A general practice method for diagnosis of
      fresh rupture of the anterior cruciate ligament].
AB  - A prospective, arthroscopic controlled study was performed to evaluate the
      usefulness of mancal sonometry of the knee in the diagnosis of acute rupture of
      the anterior cruciate ligament (ACL). In 58 patients with an acute knee injury, a
      maximum of 30 days elapsed between accident and clinical examination
      (Lachmantest, pivot-shift/ McIntosh, 90 degrees anterior translation), manual
      sonometry and functional X-ray examination. Afterwards all patients were examined
      by arthroscopy. Nine patients showed a partial, 38 patients a total rupture of
      the ACL. If the ACL was completely ruptured, the average difference in anterior
      translation between the contralateral and the injured knee was 3.3 mm (p < or =
      0.001). Statistical analysis showed high sensitivity (85%), specificity (91%) and
      positive predictive value (98%) for manual sonometry. Clinical examination,
      apparative sonometry and functional X-ray were, overall, less effective than
      manual sonometry in detecting ligament rupture. Manual sonometry proved to be a
      good and practicable method for assessing acute rupture of the ACL.

PMID- 9229779
TI  - [Advantages of the unreamed tibial nail in comparison with external fixator in
      treatment of grade 3 B open tibial shaft fractures].
AB  - Between 1987 and 1993, 41 grade 3B open tibial shaft fractures were treated with
      the unreamed tibial nail (URTN n = 22) or an external fixator (FIX n = 19). The
      method of treatment was left to the choice of the operating surgeon. Three below
      the knee amputations were performed, three patients died, and three were lost to
      follow-up. In all, 32 patients were followed up to union or at least for 1 year.
      There were no significant statistical differences between the two groups (P <
      0.2, chi-squared, t-test) with respect to fracture type, fracture location, age,
      gender or accompanying injuries. The URTN group showed significantly better
      results regarding time to full weight-bearing (URTN 11 +/- 4 weeks; FIX 20 +/- 11
      weeks, P < 0.01 M-W) Mann-Whitney Test, number of reoperations (URTN 1.04; FIX
      2.89; P < 0.01 M-W), isolated bone grafting (URTN 3/22; FIX 8/19; P < 0.05 chi
      squared), and average Karlstrom and Olerud score (URTN 30 +/- 4; FIX 26 +/- 5; P
      < 0.05 M-W). In all, 15/17 URTN patients and only 6/15 FIX patients achieved
      unlimited walking distance (P < 0.01 M-W). Time to bony union, infection, and
      nonunion were not significantly different between groups.

PMID- 9229780
TI  - [Spinal stabilization in extradural metastatic disease. Indications and follow-up
      of 32 cases].
AB  - Over 4.5 years, 32 patients with spinal epidural metastases were decompressed and
      stabilized. Median survival was 9.5 months. Myelopathy was the predominant
      indication (41%) for the operation, intractable pain (microinstability) the
      second most important. The type of tumor spreading and biomechanics necessitated
      ventral decompression and stabilization in 65%. Corporectomy or extensive
      laminectomy was always combined with internal fixation and bone cement. With the
      exception of six patients (5 early deaths), all patients were able to walk after
      surgery. The Karnofsky index was improved significantly from 35 to 66%. The
      longest survival time was found in breast carcinomas and myelomas. Preoperative
      radiological embolization was a keystone in the treatment. Indication for surgery
      in spinal metastases is critical and needs an interdisciplinary approach. When
      the patient is suffering from higher degrees of paresis or even paralysis, he/she
      is no longer an ideal candidate for the operation. The same applies in the
      presence of uncontrolled primary tumors and neoplastic disease of the GI tract
      and the bronchus.

PMID- 9229781
TI  - [Treatment of infection by vacuum sealing].
AB  - Between 1 January 1992 and 31 July 1995, 313 patients with acute and chronic
      infections were treated by vacuum sealing (VS). The average duration of VS
      treatment was 16.7 days, and there was an average of 3.1 changes in the VS
      system. In acute infections (n = 203) the wounds were closed by secondary
      suturing (65.5%), spontaneous epithelialization (17.2%), skin grafting (12.3%)
      and flap transfer (2%). Six patients died (3%). Infection recurred in 3.9% and
      was cured by another VS treatment. Unstable scar formations (1%) were treated by
      free flap transfers. When compared with standard open-wound treatment, the low
      cost VS technique offers great advantages with regard to hospital hygiene,
      patient comfort and therapeutic results.

PMID- 9229782
TI  - [56th Annual Meeting of the American Association for the Surgery of Trauma. 19-21
      September 1996, Houston, USA].

PMID- 9229783
TI  - [Thrombosis in trauma and orthopedic surgery. Prevention, diagnosis, therapy].

PMID- 9229784
TI  - [Missed diagnosis in delayed recognition of bilateral simultaneous rupture of the
      quadriceps tendons].
AB  - In this article we report a very rare case of simultaneous and bilateral rupture
      of the quadriceps tendon in a 38-year-old patient. The initial diagnosis was
      "herniated vertebral disk". Although there was an extensive neurological and
      psychiatric examination in combination with several operations, it took almost 3
      months until the real reason was found. In this case report we describe our
      postoperative treatment of early mobilization and compare it with other
      therapies.

PMID- 9229785
TI  - [Mediators and antagonists in therapy of multiple trauma. Reliable outcome or
      wishful thinking?].
AB  - The response of the immune system to any trauma starts at the moment of injury.
      Macrophages are activated and produce proinflammatory mediators. All the stimuli
      of the cytokine system lead to a final common pathway where a therapeutic
      approach might start. However, any strategy of cytokine therapy cuts both ways.
      There are a lot of data derived from in vitro and animal studies. Both the
      classification and the clinical application of these results are rather
      difficult. Some therapeutic concepts seem promising, but the advantages and
      disadvantages have to be carefully considered. The aim of all strategies must be
      to improve or adjust the patient's immune defence system. First of all, the
      patient, the disease or the specific injury has to be treated, not only the
      mediators and cytokines. The philosopher's stone has not been found yet. There
      are several approaches, but it is still a long and difficult process to find new
      insights and effective treatments.

PMID- 9229786
TI  - [Harvesting the heart for preparation of heart valve allografts].
AB  - Allograft heart valves (AHV) are believed to be optimal prosthetic material for
      surgical aortic valve and/or root replacement and an ideal valved conduit for
      repair of some complex congenital heart defects. At the University Hospital Motol
      AHV were clinically used since 1983 (annually no more than twenty were
      collected). 1991 the Paediatric Transplant Centre was established and was
      entrusted to organise cadaveric hearts harvesting and to introduce the standard
      technology of AHV processing and banking. The results of co-operation with other
      Transplants Centres, as well as with coroners and forensic medicine specialists
      in 1992-1995 are presented. For the AHV processing 274 cadaveric hearts were
      collected in the Czech and Slovak Republics, 32 of them (11.7%) came from routine
      post-mortem and 242 (88.3%) were retrieved from multiorgan harvesting, 14 hearts
      were excluded for technical reasons and another five for the seropositivity of
      the donor (three HBSAg, one HCV and one VDRL). Another 14 AHV were not suitable
      for clinical use because of a congenital lesion (bicuspid aortic valve) or
      acquired pathology found during the AHV processing (advanced atherosclerosis) or
      retrospectively diagnosed at donors post-mortem (in vivo undiagnosed malignancy).
      The technology of processing, cryopreservation and banking of AHV as well as the
      clinical use of the tissue will be discussed separately.

PMID- 9229787
TI  - [Preparation, storage, transportation and use of heart valves for
      allotransplantation].
AB  - Thanks to the co-operation with Czech and Slovak Transplant Centres and with some
      of the Departments of Pathology and Forensic Medicine 274 hearts were collected
      for allograft heart valves (AHV) processing during 1992-1995. The Cardiac surgeon
      dissected the aortic valve with the root and the pulmonary artery trunk with the
      valve. Tissues were antibiotically (ATB) sterilised in cultivation medium E 199
      (24 hours at 37 degrees C). ATB concentrations (mg/ml): Cepharin 0.2, Azlocilin
      0.2, Tobramycin 0.08 and Amphotericin B 0.1 for harvesting at post-mortem (P) or
      Miconazol 0.05 for sterile retrieval during multiorgan harvesting (MOH). After
      sterilisation AHV were stored at 4 degrees C. 49 AHV were infected even after ATB
      treatment-15 of 35 collected at P (43%) and 35 of 218 procured during MOH (16%)
      (p < 0.01-ch2 test). After serological screening of the donor and microbiological
      testing the AHV were released for clinical use. Most AHV were programmed cooled
      to the temperature of liquid nitrogen (-196 degrees C), in which they were stored
      at the Allograft Heart Valves Cryobank. Cryoprotection was achieved by 10%
      dimethylsulphidoxide. CONCLUSION: A technology of harvesting, processing, storage
      and transportation of AHV, was introduced. It enabled the routine use in many
      cardiac surgical units. The AHV Cryobank was established. 131 AHV were used
      clinically between 1992 and 1995 (transportation as far as 1300 km). 108 AHV
      (82.4%) were used for repair of complex congenital heart defects, while 23
      (17.6%) were used for aortic valve and/or root replacement.

PMID- 9229788
TI  - [Transposition of the basilic vein in the arm for vascular access in
      hemodialysis].
AB  - The author presents an account on a less frequently used vascular approach
      suitable in particular in patients with repeated a-v shunts. The group comprises
      10 patients operated in 1994-1995. The patency up to one year was 80%, after two
      years 7 shunts are patent, one female patient died one year after establishment
      of the shunt with the shunt in a functional state. One shunt closed after six
      months and the second one 11 months after operation. Complications were recorded
      in three patients, in none of them abolition of the shunt was necessary. Based on
      the author's experience and data in the literature the authors assume that this
      approach is a useful alternative to secondary vascular approaches with better
      results than those of vascular prostheses.

PMID- 9229789
TI  - [The inferior epigastric artery. Short-term and one-year patency].
AB  - The authors analyse the advantages and disadvantages of revascularization of the
      myocardium via the arteria epigastrica inferior. They submit short-term and one
      year results in a group of 18 patients operated in 1992-1995. The short-term
      patency of the arteria epigastrica inferior was in the investigated group 87.5%
      and the one-year patency 83.3%. The limiting factor of this graft are technical
      problems associated with the establishment of the central anastomosis. The
      authors assume that the epigastric artery has its place in coronary surgery,
      although at present it is used mostly as a an alternative graft, mainly for the
      recascularization of less important coronary vessels.

PMID- 9229790
TI  - [Extensive metastases in the thoracic wall as an unusual manifestation of
      malignant hepatoma].
AB  - In a 53-year-old man an extensive tumour of the thoracic wall was extirpated. It
      was examined histologically and identified as a secondary of a malignant
      hepatoma. In the second stage a primary hepatic tumour was removed by extended
      right-sided lobectomy. The case-history provides evidence of a remote secondary
      of a malignant hepatoma and a successful palliative approach.

PMID- 9229791
TI  - [The laparoscopic fundoplication technique and postoperative complications].
AB  - The authors performed in the course of 3 years 200 laparoscopic fundoplications
      on account of oesophageal reflux. Only in one case they used the classical
      approach and once they converted to the classical procedure. The short-term
      results are encouraging. The number of complications was comparable with those
      reported abroad. A complete antireflux effect was achieved in 95% of the operated
      patients. In the authors opinion the main success of the operation is the sparing
      dissection of the hiatus, maximum sparing of the vagus innervation, the creation
      of a sufficiently large window behind the oesophagus and differentiated use of
      antireflux plastic operations, depending on the preoperative examination and the
      peroperative finding. The authors prefer the circular Nissen-Rossetti plastic
      operation, they do not use antitelescopic suture nor severing of the vasa brevia.
      To prevent penetration of the stomach into the mediastinum they use only in major
      diaphragmatic defects sparing suture of the hiatus or fixation of the upper
      suture of the cuff to the top of the hiatus. They resolve major defects by
      implantation of a net into the hiatus. Their favourable results make, when
      comparing conservative and surgical treatment, laparoscopic fundoplication the
      most desirable procedure.

PMID- 9229792
TI  - [Safe preparation of the hiatus--conditio sine qua non].
AB  - The authors discuss the method of laparoscopic fundoplication which is becoming
      the method of choice for surgical treatment of oesophageal reflux. They analyse
      crucial points of the operation with regard to its safety.

PMID- 9229793
TI  - [Repeat laparoscopy in the management of biliary leaks after laparoscopic
      cholecystectomy].
AB  - The incidence of bile leaks increased with the introduction of laparoscopic
      cholecystectomy in surgery. The present paper is focused on biliary leaks-their
      diagnosis and treatment in a large group of patients, with special emphasis on a
      miniinvasive approach. Nine biliary leaks were found (i.e. 0.72%). Four leaks
      resolved spontaneously, five were treated surgically with good results.

PMID- 9229794
TI  - [Initial experience with anorectal manometry with the PC Polygraf apparatus in
      surgery].
AB  - The authors present their initial experience with anal manometry using a PC
      Polygraph of Synectics Medical Co. They discuss the manometric examination of 14
      patients with ulcerative colitis, incl. 12 who were operated. In all 12 patients
      an ilea-pouch-anal anastomosis was made. By manometry a postoperative drop of
      pressures at rest was found and partly also of pressures during muscular
      contraction as well as shortening of the zone of high anal pressure. The
      resulting values, however, did not influence continence, except for temporary
      soiling, the frequency of bowel movements being 2-8. Anal manometry is an
      important objective examination of the sphincter function as it makes it possible
      to compare values before and after therapy. It must be however combined with
      other anorectal physiological tests such as endosonography, EMG, defaecography
      etc.

PMID- 9229795
TI  - [Theodor Billroth (I. and II.)].
AB  - The two parts of the paper present a brief account of the life, work, time and
      social impact of the great surgeon Theodor Billroth. The first part deals with
      Billroth's scientific development and main parts of his life-long work. The
      second part presents Billroth as a universal genius who was engaged in the
      cultural and social life of his time and thus opened the road for surgery.

PMID- 9229796
TI  - Current diagnosis and treatment of patients with cardiac arrhythmias - a
      guideline. South African Society of Cardiac Practitioners Annual Ses . Karos
      Indaba Hotel, Johannesburg, 20-23 July 1995.

PMID- 9229797
TI  - [Detection of t(15;17) using cytogenetic, fluorescent in situ hybridization, and
      molecular techniques. Comparative study of 11 patients with acute promyelocytic
      leukemia].
AB  - OBJECTIVES: Analysis and comparison of the sensitivity for the detection of t(15;
      17) with conventional cytogenetic (CC), Southern blotting (SB), metaphase
      fluorescence in situ hybridization (M-FISH), interphase fluorescence in situ
      hybridization (I-FISH) and polymerase chain reaction (PCR) techniques. PATIENTS
      AND METHODS: 11 acute promyelocytic leukaemia (APL) patients (9 M3 and 2 M3v)
      were studied at diagnosis and partial remission and analyzed with CC (11 cases),
      SB (7 cases), I-FISH (2 cases) and PCR (3 cases) techniques. RESULTS: The
      percentages of detection of t(15;17) were: 90.9% (CC), 71.4% (SB), 85.7% (M-FISH)
      and 100% (I-FISH and PCR). Additional chromosomal abnormalities were detected in
      2 cases with CC techniques. CONCLUSIONS: 1.- There is a very good correlation in
      the detection of t(15; 17) between the techniques analyzed. 2.- At diagnosis,
      partial remission and relapse, M-FISH and PCR provide a reliable diagnosis of
      t(15; 17). Nevertheless, it is important to perform a CC analysis because it
      enables the recognition of additional chromosome abnormalities with putative
      prognostic importance. 3.- At complete remission, I-FISH and PCR provide a rapid
      and safe screening of putative residual cells. 4.- The great sensibility of the
      techniques available for the detection of t(15; 17) translocation allows the use
      in each laboratory of the most appropriate techniques according to their
      substructure and the patients' clinical stage.

PMID- 9229798
TI  - [Evaluation of bone-marrow cell cryopreservation using long-term cultures].
AB  - PURPOSE: Autologous bone marrow transplantation (ABMT) is frequently used in the
      treatment of neoplastic diseases. It involves several manipulations of bone
      marrow cells in vitro that can damage the stem cells responsible for grafting.
      Long-term marrow cultures (LTBMC) support hematopoiesis in vitro for several
      weeks. We analyzed the effect of bone marrow cryopreservation on haematopoiesis
      when using this technique. PATIENTS AND METHODS: 9 bone marrow from healthy
      donors (Group A) and 15 from patients who were about to undergo ABMT (Group B)
      were assayed in LTBMC. In all cases, cultures were initiated after cell
      concentration and also after cryopreservation in group B patients. Adherent cell
      layer formation, supernatant nucleated cell counts and CFU-GM growth from the non
      adherent fraction were assessed. Statistical analysis were evaluated using
      Wilcoxon test for paired results and Mann-Whitney test for unpaired results.
      RESULTS: No significant statistical differences were observed when the LTBMC from
      group A controls were compared to those from group B patients prior to cell
      cryopreservation. There was a significant statistical difference between
      cumulative cell recoveries among the cultures developed prior to and after
      cryopreservation of BM cells from group B patients. CONCLUSION: The results
      supports the use of LTBMC to obtain information on the extent of the injury of BM
      cells during manipulations.

PMID- 9229800
TI  - [Automated hematology: its evolution envisioned by "an old hematologist"].

PMID- 9229799
TI  - [Immunohematologic study and transfusion approach to patients with public
      antibodies].
AB  - OBJECTIVES: To analyze the different immunohematologic studies required to
      identify anti-red cell antibodies directed against high incidence antigens and
      comment the best tranfusion management. PATIENTS AND METHODS: Five patients with
      suspected anti-red cell alloantibodies directed against high frequency antigens
      are reported. After a positive antibody screening test (AST), an agglutination
      test with a commercial panel of 24 red cells was performed. Red cells were
      treated with proteolytic enzymes and AET to try to identify the circulating
      antibody. However, it was necessary to send the samples to reference laboratories
      for definitive identification. In order to evaluate the haemolytic potential of
      the antibody serum samples were treated with DTT and immunoglobulin subtype was
      studied with the capillary agglutination test. Finally, we analyze the half life
      of Cr51 labelled red cells. To obtain compatible blood for transfusion,
      autologous transfusion and cross-match with blood from direct relatives were
      performed. RESULTS: AST was positive in every case. A decrease in the
      agglutination test was observed after ficin treatment in two patients, and an
      increase in the remaining. The treatment of red cells with ZZAP and AET resulted
      in a decrease of agglutination in three cases and an increase in the remaining
      two. Specificity of the antibodies was as follows: anti-Cellano (two cases), anti
      Ku (one case) and anti-Yta (two cases). Anti-Kell antibodies were IgG1 and anti
      Cartwright antibodies were IgG4. One patient was transfused with autologous blood
      alone, another patient received compatible blood from direct relatives. A third
      patient was transfused both with autologous and allogeneic compatible blood. The
      fourth patient did not need red cell transfusion and, finally the last patient
      had to be transfused with incompatible blood but no postransfusion haemolysis was
      observed. CONCLUSIONS: In patients with anti-red cell antibodies against high
      frequency antigens, red blood cells treatment with proteolytic enzymes (ZZAP,
      ficin) and AET are useful techniques to approach to their identification. Beside
      this, the study of type and subtype of Ig are necessary to know the haemolytic
      activity of the antibody. Regarding the transfusional management, autologous
      transfusion, crossmatch with blood from direct relatives and cryopreservation of
      compatible blood are the most adequate attitudes to cover future needs.

PMID- 9229801
TI  - [Evaluation of the Coulter MAXM. Differential leukocyte count and left-shift
      alarm].
AB  - PURPOSE: To assess the reliability of the differential leucocyte count (DLC) and
      the left shift flagging (LSF) system provided by the Coulter MAXM (MAXM)
      haematology analyzer. MATERIAL AND METHODS: 380 blood specimens (drawn with tri-K
      EDTA as anticoagulant) were studied. RESULTS: By using the reference method
      (NCCLS H20-A), 50 out of the 380 blood specimens presented abnormal DLC (bands >
      6%). Of from these, in 39 (80%) the MAXM displayed LSF of "bands 1 or 2". In 118
      left shift flagged specimens (MAXM) with normal manual DLC, 87 (74%) had the
      "bands 1" alarm and 31 (26%) the "bands 2" alarm. Accordingly if the LSF "bands
      1" is overlooked, the percentage of FP decreases from 36% to 10% but the
      percentage of false negatives (FN) increases from 22% to 58%. In order to improve
      the appreciation of LSF by decreasing the need of manual revisions, the visual
      examination of the leucocyte distribution scattergram (LDS), also provided by the
      MAXM, was conveniently evaluated. This study was performed on 190 blood specimens
      from which the MAXM displayed a normal DLC in 122 (64%), the LSF of "bands" in 44
      (23%) and the LSF of "bands 2" in 24 (12.6%). Of from the 122 specimens with
      normal DLC, four were FN, of from the 44 specimens with "bands 1" LSF, 37 were FP
      and of from the 24 specimens with "bands 2" LSF, 16 were FP. The visual
      appreciation of the LDS showed in the majority of samples with "bands 1" and
      "bands 2" a definitely different shape consisting in a sharper image up to the
      top of the picture when compared to samples with normal DLC (without flags).
      According to this criteria, all the 122 specimens with normal DLC displayed a
      normal LDS and all the 24 specimens with "bands 2" flag displayed abnormal LDS.
      Of from the 44 specimens with "bands 1" flag, 26 (59%) showed an abnormal LDS and
      18 (41%) a normal LDS. It is noteworthy that of from the 26 specimens with
      abnormal LDS only 7 were true positive (TP), whereas the 18 specimens with normal
      LDS all showed a normal DLC according to the reference method. These data allow
      us to conclude that manual revision was required in 26 out of 68 specimens with
      "bands 1" and abnormal LDS (13% of the total) and in all the 24 specimens with
      "bands 2" flag. Therefore by using the information provided by the LDS the need
      of manual revision decreases to 73% of the total sample with LSF. CONCLUSION: Our
      results give further support to the idea that th VCS method used by the Coulter
      MAXM provides a high quality DLC with specific left shift detection.

PMID- 9229802
TI  - [Cytokines and chronic B-cell lymphatic leukemia].

PMID- 9229803
TI  - [Granulocytic sarcoma as a tumor presentation of myeloid hemopathies].

PMID- 9229804
TI  - [Treatment of thrombocytopenic thrombotic purpura].

PMID- 9229805
TI  - [9th Antonio Raichs memorial lecture. Myelodysplastic syndromes].

PMID- 9229806
TI  - [Hypocholesterolemia in hematologic neoplasms].
AB  - PURPOSE: To evaluate the cholesterol metabolism in oncohaematologic patients and
      its inclusion as a biochemical marker as well as other parameters in the
      diagnostic period (leukocytes, deshidrogenase lactate, erithrosedimentation,
      haptoglobine). Many different epidemiological studies discuss the relation
      between the high risk for cancer mortality and low blood cholesterol in patients
      with colon, rectum, ovary and brain cancer as well as in chronic myeloid
      leukaemia, acute leukaemia and policytemia vera. PATIENTS AND METHODS: Two groups
      were studied: a normal group (n = 32) was confronted to a group of
      oncohaematologic patients (n = 37) (15 lymphoma, 4 acute leukaemia, 7 chronic
      myeloid leukaemia, 1 chronic myelomonocytic leukaemia, 3 policytemia vera, 5
      myeloma and 2 chronic lymphoid leukaemia). In all the cases we determinated the
      total cholesterol, HDL cholesterol, LDL cholesterol, A1 y B apolipoproteins.
      RESULTS: The means obtained in the normal group were 184.63 mg/dL, 50.34 mg/dL,
      116.38 mg/dL, 140.93 mg/dL, 79.57 mg/dL while in the pathologic group were 163.43
      mg/dL, 38.19 mg/dL, 106.60 mg/dL, 102.81 mg/dL and 101.23 mg/dL, respectively.
      There was a significant difference in the total cholesterol, HDL cholesterol and
      apolipoprotein A1. These values were lower for leukocytes higher than 10.0 x
      10(9)/L. Furthermore the lowest total cholesterol value was seen in myeloma
      patients. CONCLUSION: The cholesterol, its fractions and the apolipoproteins
      determinations might be considered as a biochemical marker while diagnostic is
      being made, since they are known to play an important role in the tumoral cell
      metabolism.

PMID- 9229807
TI  - [Granulocytic sarcoma: unusual form of presentation for acute nonlymphoblastic
      leukemia].
AB  - A case of acute non-lymphoblastic leukaemia is reported which appeared as
      granulocytic sarcoma (GS) with no leukaemic expression in peripheral blood. Aside
      of the patient's advanced age, the rarity of this entity at the onset of ANLL and
      the location of the tumour, on the back of the patient's left upper thigh are
      outstanding features. The difficult diagnosis of such non-leukaemic cases is also
      stressed here, with regard to the differential diagnosis with non-Hodgkin's
      lymphoma (NHL). It is concluded that the incidence of GS as a tumour of soft
      tissues in the extremities is more common in patients over 75 years of age, its
      frequency being 17-fold that of NHL for the same age and location.

PMID- 9229808
TI  - [Chronic myeloid leukemia developing into a multifocal extramedullary blast
      crisis].
AB  - A 47-old male with accelerated-phase chronic myelogenous leukaemia is presented.
      In spite of a good response to hydroxyurea and interferon treatment, the patient
      developed multiple foci of granulocytic sarcoma as a special form of blastic
      crisis. A review was carried out of the different aspects of this entity, stress
      being laid on the diagnostic characteristics and the current therapeutic approach
      in such cases.

PMID- 9229809
TI  - [KI-1-positive, anaplastic, large-cell lymphoma related to Hodgkin's disease].
AB  - We report a case of lymphoma associated with lung carcinoma that shows
      morphological and immunohistochemical features of anaplastic large cell Ki-1
      positive lymphoma and Hodgkin's disease, with positivity for Ki-1 (CD-30)
      (characteristic of both lymphomas) and Leu-M1 (CD-15) (normally dosent absent in
      anaplastic lymphoma). This subtype of lymphoma is designated anaplastic large
      cell Hodgkin's related lymphoma (ALCL related to HD) and is considered by some
      authors as a secondary anaplastic large-cell lymphoma.

PMID- 9229810
TI  - [Erythroblastopenia, myelodysplastic syndrome and cytogenetic study].

PMID- 9229811
TI  - [Chronic myeloid leukemia after kidney transplantation].

PMID- 9229812
TI  - [A new case of chronic neutrophilic leukemia].

PMID- 9229813
TI  - [Leukemia cutis in acute promyelocytic leukemia].

PMID- 9229814
TI  - [Chronic myelomonocytic leukemia and renal carcinoma: a rare association].

PMID- 9229815
TI  - [Mast cells in the peripheral blood as a presenting form of malignant
      mastocytosis].

PMID- 9229816
TI  - [Chylothorax as a complication of chronic lymphatic leukemia].

PMID- 9229817
TI  - [Agranulocytosis secondary to acute hepatitis B with a good response to G-CSF].

PMID- 9229818
TI  - [A functional-morphological study of the mucociliary system at stages in the
      disease in patients with chronic bronchitis].
AB  - Combined morpho-functional study of the mucociliary system in patients with
      chronic bronchitis at different stages of its development was made. Regional
      mucociliary clearance was evaluated by dynamic aerosol scintigraphy and electron
      microscopy. Radiography of bronchial biopsies was performed, rheological
      properties of bronchial content were also determined. Special characteristics of
      mucociliary main chains were established at each stage of chronic bronchitis
      development as well as depending on the type of bronchitis, bronchial tree level
      and phase of the disease. New hypothesis on chronic obstructive bronchitis
      genesis was substantiated.

PMID- 9229819
TI  - [The treatment of patients with chronic obstructive bronchitis by using a low
      power laser at a general rehabilitation center].
AB  - 100 patients with chronic obstructive bronchitis were examined and treated in the
      therapeutic department of rehabilitation center. Combined treatment including low
      energy laser radiation produced good results. Laser therapy has improved
      bronchial permeability, sensitivity of bronchial beta 2-receptors to
      sympathomimetics. As a result, their intake was reduced or discontinued. Laser
      radiation combined well with other non-pharmacological modalities.

PMID- 9229820
TI  - [The characteristics of the clinical course and treatment of chronic obstructive
      lung diseases against a background of lymphoproliferative diseases].
AB  - The authors studied expectoration, cough clearance and immunity in 48 patients
      with exacerbation of chronic obstructive pulmonary affections (COPA) associated
      with lymphoproliferative diseases (chronic lymphoid leukemia, lymphocytic
      lymphoma, myeloma) versus 16 control patients suffering from COPA alone. patients
      of the test group received cytostatics and steroids according to standard
      schemes. They are shown to develop aggravation of immune defects with emergence
      of persistent secondary immunodeficiency, more marked disturbance of
      tracheobronchial clearance with more frequent occurrence of persistent ciliary
      dyskinesia. This resulted in slower relief of clinical symptoms, more severe
      course dictating the necessity of longer treatment, the addition of
      immunocorrectors, antibacterial drugs without immunosuppressive action.

PMID- 9229821
TI  - [The morphometric characteristics of the blood and sputum eosinophils in
      bronchial asthma patients].
AB  - The authors investigated principal morphometric parameters of peripheral blood
      and sputum eosinophils in 18 patients with moderate bronchial asthma receiving
      combined treatment, in healthy donors and BA patients treated for a long time
      with sodium cromoglycate (SC). In BA exacerbation there appeared eosinophils with
      large-size cells, cytoplasm and nucleus. The treatment resulted in a decrease in
      the cell and cytoplasm area, enlargement of the nucleus. SC cause morphometric
      alterations in eosinophils. The change in morphometric characteristics of the
      blood and sputum eosinophils, relationships between different cell
      characteristics in the course of treatment evidence for alterations of synthetic
      processes in the blood and sputum eosinophils, for replacement in cell the cell
      pool.

PMID- 9229822
TI  - [R proteins in the assessment of the inflammation in bronchial asthma].
AB  - Serum R-protein titers were determined in 106 patients with mild, moderate and
      severe bronchial asthma. The titers were found high, their elevation being in
      close correlation with absolute blood count of eosinophils and severity of
      clinical symptoms.

PMID- 9229823
TI  - [The efficacy of inhaled glucocorticosteroids in different dosage regimens and in
      combination with theophylline preparations in bronchial asthma patients].
AB  - The authors compare basic body plethysmography and peak flowmetry parameters,
      quality of life in 37 patients suffering from moderate or severe bronchial
      asthma. They received for 8 months low-dose glucocorticosteroids (group 1), high
      dose glucocorticosteroids (group 2) and combination of low-dose
      glucocorticosteroids with long-acting theophyllin drugs (group 3). All the
      parameters assessed, quality of life was better in groups 2 and 3 (p < 0.05).
      Patients from these groups had also less frequent exacerbations of the disease
      which appeared less severe. From group 3 patients those who suffered longer and
      had marked emphysema showed a greater response.

PMID- 9229824
TI  - [The effect of polyunsaturated fatty acids of the omega-3 class on the late phase
      of the allergic reaction in bronchial asthma patients].
AB  - Placebo-controlled study of changes in the course of atopic bronchial asthma
      (ABA) induced by supplement of the diet with polyunsaturated fatty acids of omega
      3 class in 13 patients compared to placebo-treated subjects allowed the
      conclusion on significant attenuation of late allergic response in patients who
      had taken eiconol for two weeks. The effects of the acids are explained by a
      comparative replacement of arachidonic acid in the membranes of cell effectors of
      the inflammation with omega-3 fatty acids leading to inhibition of production of
      inflammation lipid mediators.

PMID- 9229825
TI  - [The effect of polyunsaturated fatty acids on the biochemical indices of
      bronchial asthma patients].
AB  - A placebo-controlled study was made of the efficacy of diet additive of omega-3
      polyunsaturated fatty acids (diet oil eiconol) in 27 patients with bronchial
      asthma (BA). It was found that eiconol causes qualitative changes in the disease
      course: severe attacks of asphyxia occurred less frequently, drug doses were
      reduced. Provocative tests with allergen after two-week intake of eiconol versus
      placebo intake showed a significant decline of late allergic response due to
      compitative replacement of arachidonic acid in cell membranes of inflammation
      cell effectors by omega-3 polyunsaturated fatty acids inhibiting production of
      lipid mediators of inflammation.

PMID- 9229826
TI  - [The efficacy of the magnesium sulfate aerosol treatment of bronchial asthma
      patients].
AB  - Action of magnesium sulphate (MS) aerosol (solution osmolality 260 mmol/l, pH
      6.6) on bronchial sensitivity and reactivity to acetylcholine(AC) and graded
      exercise as well as bronchial permeability assessed by general plethysmography
      and pneumotaxography were studied in 49 patients with mild and moderate bronchial
      asthma. It is shown that when compared to placebo, MS inhalations conducted in
      the time of attenuating asthma exacerbation improved immediate and long-term
      responses in atopic and effort asthma. Both in single doses and course
      administration MS reduced non-specific bronchial hyperreactivity and secretory
      activity of mast cells. Positive dynamics of bronchoprovocative AC test suggested
      response to treatment in most BA patients.

PMID- 9229827
TI  - [The effect of the liposomal form of hydrocortisone on the status of cellular and
      humoral immunity in patients with steroid-dependent bronchial asthma].
AB  - The authors present the results of treatment of 78 patients with steroid
      dependent bronchial asthma. The most noticeable effect was observed in the
      patients on combined therapy including impulse irrigation of the bronchi (during
      sparing fiber bronchoscopy) with liposome and hydrocortisone as compared to the
      controls receiving this procedure with liposome without hydrocortisone, and a
      group of patients who had received systemic corticosteroids by a routine method.
      In the attack period inhibition of both cellular and humoral immunity was
      observed in all the examinees with steroid-dependent bronchial asthma who had
      received systemic corticosteroids. A positive therapeutic effect consisting in
      elimination of inflammation in the tracheobronchial tree and normalizing the
      indices of cellular and humoral immunity was observed earlier in patients
      receiving therapeutic fiber bronchoscopy with liposome and hydrocortisone. The
      efficacy of the use of impulse irrigation of the bronchi with liposome in steroid
      dependent bronchial asthma was emphasized.

PMID- 9229828
TI  - [The effect of positive end-expiratory pressure on respiratory biomechanics in
      bronchial asthma].
AB  - The influence of PEEP breathing has been studied in 43 patients with exacerbation
      of bronchial asthma (BA) during 20 min in resistance of 5, 7 or 9 sm. Sputum
      expectoration and inspiration were found improved after PEEP breathing. Moreover,
      in some patients mild BA attacks relieved. Lung hyperinflation, bronchial
      obstruction reduced. A positive effect was observed in moderate asthma in PEEP
      breathing of 7 and 9 sm more frequently. This, PEEP breathing can be applied in
      the treatment of BA.

PMID- 9229829
TI  - [A hyperventilation syndrome in a patient with hereditary mesenchymal dysplasia].

PMID- 9229830
TI  - [The relationships between the broncholytic and diuretic effects of theophylline
      in patients with obstructive lung diseases combined with oxalosis].

PMID- 9229831
TI  - [Chronic obstructive bronchitis (its definition, etiology, pathogenesis, clinical
      picture and therapeutic program)].

PMID- 9229832
TI  - [The use of a new marker and test systems for the diagnosis of lung cancer with a
      study of bronchoalveolar washings].
AB  - Diagnostic value of enzyme immunoassays and immunoagglutination kits based on
      monoclonal antibodies ICO 25 was investigated. Antigen CAg 25 occurred in minimal
      quantities (5 micrograms/ml maximum) or was absent in the bronchoalveolar lavage
      of patients with bronchial asthma, chronic bronchitis or free of pulmonary
      affection. The concentration 9-19 micrograms/ml was registered in epidermoid
      bronchial cancer and peripheral lung cancer. It is stated that test systems able
      to detect a new antigen CAg 25 in BAL are diagnostically significant.

PMID- 9229833
TI  - [Atrial fibrillation and the short P-Q interval syndrome].

PMID- 9229834
TI  - [The effect of different factors on cardiac rhythm variability in patients with
      arterial hypertension].
AB  - The purpose of this study was to evaluate the influence of different factors,
      among them left ventricular hypertrophy (LVH) on long-term heart rate variability
      (HRV) in patients with hypertension. 38 patients with arterial hypertension of
      different genesis were included in the study. Ischemia was excluded in all the
      patients by the data of clinical and instrumental methods of investigation. LVH
      data obtained from HRV of 20 healthy subjects was used as control. HRV was
      evaluated by estimating variations for short intervals of a rhythmogram (VSI). A
      HRV decrease did not depend on sex, but essentially depended on patients'a age,
      disease duration and the form of hypertension. A marked tendency leading to the
      rate variability decrease was observed only in moderate LVH. In cases of original
      LVH variability data did not differ from those in patients without signs of LVH.
      Low or marginal HRV was more often observed in patients with essential
      hypertension and in those with hypertension of endocrine genesis. As far as renal
      hypertension is concerned low variability was less frequent. There were a lot of
      factors which affect the change of HRV. The more significant of them were the
      patients' age, hypertension genesis and form of hypertension. Factors leading to
      the rate variability decrease were the following age above 40, endocrine or
      essential hypertension and moderate form of hypertension.

PMID- 9229835
TI  - [The effect of the new angiotensin-converting enzyme inhibitor moexipril on the
      circadian rhythms of arterial pressure in hypertension patients].
AB  - 24-hour monitoring of arterial pressure was performed before, 3 and 9 weeks after
      moexipril treatment (daily dose 7.5-15 mg) for mild and moderate hypertension. Of
      15 patients treated 66.6% responded to the 9-week course. Adjuvant hypothiazid
      elevated the effect to 73.6%. Moexipril lowered mean 24-h diastolic pressure
      without changing the 24-h pressure curve or heart rate. Antihypertensive
      moexipril effect was higher in the day time. Variability of diastolic arterial
      pressure was lower at night.

PMID- 9229836
TI  - [A clinico-pharmacological study of the antianginal and anti-ischemic efficacy of
      a new drug form of diltiazem with delayed release].

PMID- 9229837
TI  - [Aspirin-induced asthma (its clinical picture, pathogenesis and treatment)].

PMID- 9229838
TI  - [The role of nitric oxide in regulating pulmonary functions].

PMID- 9229839
TI  - [Humoral transport of the bronchi and its correction in bronchial asthma].

PMID- 9229840
TI  - [The hantavirus pulmonary syndrome (its etiology, epidemiology, pathogenesis,
      clinical manifestations and the diagnosis of a new infectious disease)].

PMID- 9229841
TI  - [The importance of coronary angiography in patients with an acute myocardial
      infarct].

PMID- 9229842
TI  - [Chronic obstructive lung diseases: the diagnostic problem].

PMID- 9229843
TI  - [The functional activity of pulmonary surfactant in chronic bronchitis].
AB  - Lung surfactant (LS) was examined in the course of chronic bronchitis (CB)
      development in 25 subjects with CB risk factors (RF), 80 with prebronchitis (PB),
      30 with chronic non-obstructive bronchitis (CNOB) and 45 with chronic obstructive
      bronchitis (COB). Biochemical study of the expirates covered total phospholipids
      (TP), fractions of neutral lipids, several fatty acids (FA), malonic dialdehyde
      (MDA), antiradical activity (ARA). Development of CB was accompanied with shifts
      in LS functional activity. In patients with RF the shifts reflected adaptation.
      In PB, CNOB and COB patients LS got damaged. The damage was detected by
      biochemical markers: elevated level of polyunsaturated FA, accumulation of MDA
      and low ARA.

PMID- 9229844
TI  - [Determination of the content of common protein in biological samples using
      chemical stabilizers].
AB  - Proteins of biological samples in the process of storage are subject to microbe
      contamination as well as the destruction by their own lipoprotein lipases. It is
      established that N-thymol compounds of formulas 52 and 82 stabilize blood serum
      samples of donors and preserve the content of total protein in them unchanged for
      7, 15 and 40 days, respectively. The obtained stabilizers can be used when
      studying protein metabolism in the organism of cosmonauts performing long-term
      space flight, depots of nuclear submarines, participants of long-term Alpine,
      desert, polar and other expeditions.

PMID- 9229845
TI  - [Research of Academician O.V. Palladin and his school in the field of
      biochemistry and physiology of muscles].
AB  - The paper deals with the history of development of one of the basic trends in
      scientific activity of Academician O. V. Palladin and world-known biochemical
      school created by him: biochemistry and physiology of muscular activity.
      Retrospective analysis of the works by O. V. Palladin and his pupils, dedicated
      to the mentioned problem permits judging of realization of his ideas, when
      studying the process of training, work to fatigue by means of determining the
      content of energy sources in muscles (creatine, creatine phosphoric acid,
      carnosine cholesterin, glycogen), some redox enzymes (catalase, dehydrogenases),
      lactic acid, vitamins (ascorbic acid, B1). It is emphasized that the scientific
      legacy of O. V. Palladin's school is of great practical importance for rational
      substantiation of regimes of physical loads of sportsmen and physical culture
      men, production sphere workers. The works of this school have exerted
      considerable influence on the solution of labour physiology problem.

PMID- 9229846
TI  - [Organization and development of neurochemical research in the Dnepr area (the 60
      80s)].
AB  - The development of neurochemical investigations at the Institute of Biochemistry
      of the National Academy of Sciences of Ukraine initiated by Academician A. V.
      Palladin, has impelled specialists in some regions of the country to start
      research in this trend. The Department of Biophysics and Biochemistry of
      Dniepropetrovsk State University founded and headed by Professor O. D. Reva
      became one of such centres in the Dnieper area. The chief developments of
      scientific-research inventions were devoted to radiational neurochemistry, O. D.
      Reva should be accounted as a pioneer of the study of chemical composition and
      metabolism in functional and morphologically logically different sites of cats
      spinal cord lumbar enlargement. Thus, the significant statement, proposed by A.
      V. Palladin, was confirmed about the presence of biochemical differentiation in
      cerebrum besides the morphological and functional ones. While analysing the test
      data concerning the biochemical and biophysical indices of roentgen irradiation
      of cats in different terms and conditions an original scheme of radiation
      biophysical and radiation-biochemical injury of spinal cord was proposed. Some
      tissue proteinases, as well as some neurospecific proteins in the norm and under
      the gamma-irradiation were selected and assayed. An immunoelectrophoretic
      technique for estimating glyolic fibrilar acid protein and cellular adhesion (N
      CAM) in blood and surrounding fluid, as well as in human brain tumour was
      developed and a method of early prenatal diagnosis of embryo developmental
      disorders was proposed in order to prevent the birth of the underdeveloped
      infants.

PMID- 9229847
TI  - [Inhibition of cholinesterases of varying origin by ordinary and betaine
      vinylphosphates].
AB  - The comparative study of irreversible inhibitory action of some substituted vinyl
      phosphates (in usual and betaine forms on cholinesterases from different
      biological sources such as the human blood erythrocytes, the horse and the hen
      blood serum and optic ganglia of the squid) has been carried out. It is shown
      that betaines obtain lesser inhibitory activity as compared with the
      corresponding ordinary vinylphosphates. Some of tested inhibitors display
      expressed selectivity of action. So, the compound GL-2 reacts with cholinesterase
      of optic ganglia of the squid 450 000 times faster than with cholinesterase of
      the hen blood serum. The application of vinylphosphates as inhibitors of
      cholinesterases allows displaying additional differences in properties of
      enzymes. It is very important for comparative enzymology. These compounds may be
      used for detalization of type belonging and to make the classification of
      cholinesterases more accurate. Moreover, the estimation of anticholinesterase
      activity of vinylphosphates is important because these compounds may be used both
      in medicine and agriculture.

PMID- 9229848
TI  - [Effect of withdrawal of phenazepam and nicotinamide on the status of the system
      of reception of benzodiazepines and NAD].
AB  - Comparative investigations in reception of NAD, benzodiazepines and GABA by
      synaptic membranes under a single and multiple administration of phenazepam and
      nicotinamide to animals as well as after withdrawal of long-term administration
      of these drugs have been carried out. The both drugs activate GABA-inhibiting
      system of synaptic membranes. Both the sections of specific binding of
      benzodiazepines and of NAD take part in realization of "cancellation" syndrome.
      Chronic administration of phenazepam and nicotinamide results in the change of
      coupling in GABA-benzodiazepine receptor complex. After the withdrawal of chronic
      administration of nicotinamide the function of GABA-benzodiazepine receptor
      complex is normalized more quickly.

PMID- 9229849
TI  - [Treatment of intact myometrial cells with oxytocin inhibits Mg2+, ATP-dependent
      accumulation of Ca2+ in endoplasmic reticulum].
AB  - Uterotonic peptide hormone oxytocin has been studied for its effect on ATP
      dependent accumulation of Ca2+ nonsensitive to the effect of ruthenium red (10
      microM) that is potentiated by Ca2+-precipitating anion - oxalate. That was
      studied in experiments made on the suspension of myometrium cells from
      estrogenized rats processed by digitonin (0.1 mg/ml) with the aim
      permeabilization of plasmatic membrane. The preliminary processing of intact
      myocytes by oxytocin solution (final concentration 100 mM) to permeabilization of
      plasmatic membrane causes partial inhibition (stimulated by oxalate by 25-30% (0
      10 mM) of Mg2+, ATP-dependent accumulation of Ca2+ in nonmitochondrion
      intracellular calcium depot of perforates smooth-muscled cells. The value of the
      component of power-dependent accumulation of Ca2+, that is inhibited by oxytocin,
      increased with both the incubation time and oxalate concentration. Thapsigargin
      and cyclopiasonium acid, selective inhibitors of calcium pump of
      endo(sarco)plasmatic reticulum, when used in saturation concentration (50 mM and
      10 mM, respectively), completely inhibit the component of Mg2+, ATP-dependent
      accumulation of Ca2+ in nonmitochondrial intracellular calcium depot that is
      stimulated with oxalate (< 10 mM) and inhibited with oxytocin (100 mM). It is
      concluded that oxytocin partially inhibits Mg2+, ATP-dependent calcium pump of
      myometrium cell endoplasmic reticulum.

PMID- 9229850
TI  - [Interaction of precursors of secretory proteins and components of a cell-free
      protein-synthesizing system with phospholipid membranes].
AB  - Translocation of eucaryotic secretory proteins across the phospholipid membrane
      containing, no protein components has been studied on the model system. The level
      of translocation was found to depend critically on physical and chemical
      properties of membranes. It was found that the cell-free system components can
      exhibit membrane activity.

PMID- 9229851
TI  - [Interaction of ribosomes with membranes in vitro].
AB  - Fluorescent "fusion-reporting" probe (R18) was used to study the interaction of
      ribosomes with membranes in vitro. The latter was incorporated both in the
      membranes, and ribosomes. The interaction of R18-labeled ribosomes with non
      labeled liposomes (of different size and composition) or microsomes increased the
      fluorescence observed, i.e., the dilution of fluorescent probe took place. The
      dependence of interaction process on the change of liposomes indicates that the
      interaction between ribosomes and negatively charged liposomes was more
      efficient, than that with neutral ones. It is shown that ribosomes can interact
      with phospholipid membranes even after degradation of protein components
      accessible for proteins. The interaction of R18-labeled membranes with non
      labeled ribosomes results in the increase of fluorescence too. Results obtained
      indicate to the possibility of direct interaction between ribosomes and
      membranes.

PMID- 9229852
TI  - [Effect of stress on lipid peroxidation and physico-chemical status of
      endoplasmic reticulum membranes in liver of adult and old rats].
AB  - As a result of experiments carried out on adult (6-8 months) and old (24-26
      months) male rats of the Wistar line it is established that emotional-pain stress
      results (in one day) in essential increase in the activity of spontaneous, NADPH-
      and ascorbate-dependent peroxidation of lipids in the liver microsomes, which is
      expressed in the old animals rather than in the adult ones. The induced
      peroxidation of lipid six days after the stress effect remains activated in the
      adult rats and decreases to the control level in the old ones. Accumulation of
      lipoperoxidation products in the membrane structure of hepatocytes is accompanied
      by the changes of physico-chemical parameters of microsomal membranes,
      microviscosity and surface potential in particular. Availability of
      conformational shifts of membrane proteins of microsomes under the conditions of
      lipoperoxidation activation evoked by the stress is accompanied by changes of
      physico-chemical parameters of microsomal membranes. Changes in the membrane
      structure are expressed to the less extent in the microsomes of old rats liver as
      well, that evidences for the age-dependent differences of adaptational capacities
      of the organism.

PMID- 9229853
TI  - [Effect of L-carnitine on lipid peroxidation and lipid composition in blood serum
      in hemic hypoxia].
AB  - Sodium nitrite has been studied for its effect on lipid metabolism of Wistar line
      rats. It is shown that a single administration of sodium nitrite in account 5 mg
      per 100 g of the body weight results in the intensification of lipids
      peroxidation, hyperbetalipoproteinemia, hypertriglyceridemia,
      hypercholesterolemia and to the decrease of the coefficient
      phospholipids/cholesterin/. Prophylactic administration of carnitine chloride in
      account of 20 mg per 100 g of the body weight stabilizes the level of lipids
      peroxidation, decreases concentration of total lipids, triglycerides, total
      cholesterin, phospholipids, lipoproteids of low and very low density, in the rat
      blood serum, normalizes the coefficient phospholipids/cholesterin.

PMID- 9229854
TI  - [Effect of cations of transition metals on respiration and H+ production in liver
      mitochondria].
AB  - Results obtained prove that respiration stimulation of mitochondria Ca2+, Sr2+,
      Mn2+ is determined by transport of these cations to the indicated subcellular
      structures with participation of Ca2(+)-uniporter. Effect of Cd2+ on respiration
      of mitochondria is of two-phase character. Concentration of Cd2+ being above 100
      microM the stimulation phase is accompanied by the further inhibition of
      mitochondria respiration. La3+ inhibits respiration of mitochondria. However La3+
      and Cd2+ stimulate H+ production by mitochondria, that is not blocked by
      ruthenium red (10 microM). Probably, the effect of La3+ and Cd2+ on respiration
      of mitochondria is determined by the change of proton conductivity of
      mitochondrion membrane. Direct inhibiting effect of Cd2+ on the respiration chain
      of mitochondria has been established.

PMID- 9229855
TI  - [Anti-cataract activity of a vitamin E analog].
AB  - Anti-cataract activity of vitamin E analog with shortened side chain--2'-4'
      methyl-pentenyl-acetoxy-2,5,7-tetramethylchroman has been studied. It is shown on
      the model system that the analog of vitamin E inhibits the increase of the lens
      agent fluorescence under irradiation of its homogenates by polychrome light.
      Taking no negative effect on the lens capsule epithelium, the drug normalizes the
      content of vitamin E in the blood and increases activity of Na+, K+, ATPase in
      the cortex and capsule of rabbits lenses in dynamics under simulation of light
      cataract in vivo.

PMID- 9229856
TI  - [Effect of trental on collagen proteolysis in experimental aseptic infarction of
      the lone bone].
AB  - Dynamics of biochemical parameters of the connective tissue and morphometric
      parameters of lesion were studied in rabbits with induced embolic aseptic
      infraction of the femur without and with the trental (pentoxiphylline) treatment.
      The correlation was found between the pairs of indices: proteolytic activity and
      bone marrow necrosis volume: collagenase activity and bone cortex remodelling
      rate: concentration of protein bound with hydroxyproline fraction and endosteal
      regenerate volume.

PMID- 9229857
TI  - [Chromatin-protective action of the biologically active preparation BTK-8L in
      tetrachloromethane and chlorophos poisoning].
AB  - Results obtained from the study of the interaction between the phytosteroid
      preparation (BTK-8L) and fractionated rat liver nuclear chromatin under
      conditions of the tetrachloromethane and chlorophos intoxications are described.
      It is shown that preventive injection of BTK-8L to the animals has a partial
      protective effect on transcriptionally active and repressed liver chromatin. This
      preparation interacts with chromatin histone proteins binding with them and
      changes the nucleoprotein complex structure as a results of which the chromatin
      fraction components become less accessible to the damaging action of
      tetrachloromethane and chlorophos. The BTK-8L protective effect is exhibited on
      the DNA replication and transcriptional levels under conditions of
      tetrachloromethane and chlorophos intoxications.

PMID- 9229858
TI  - Stoichiometry of glucose and xylose fermentation in Butyrivibrio fibrisolvens
      787.
AB  - Glucose and xylose are the principal monomeric units of plant carbohydrates.
      Butyrivibrio fibrisolvens, an important rumen bacterium, converted both sugars to
      formate, acetate, butyrate and lactate. More metabolites and less cell biomass
      was formed from xylose than from glucose. In cultures with both substrates,
      glucose was utilized preferentially. Growth on glucose was more rapid than on
      xylose. No phosphoketolase activity (EC 4.1.2.9) was detected in this strain.
      More carbohydrate and less protein was found in glucose-grown cells than in cells
      grown on xylose. Growth yields of protein were higher on xylose, in spite of the
      fact, that yields of cellular dry matter were higher on glucose.

PMID- 9229859
TI  - Levels of free gamma-aminobutyric acid and other neuroactive amino acids in
      cerebrospinal fluid of patients with neurological disorders.
AB  - Concentrations of free gamma-aminobutyric acid, other neuroactive amino acids and
      related compounds were determined in CSF of 42 patients with ischemic stroke, 8
      patients with vascular encephalopathy and 14 patients with neurological syndromes
      of spine degenerative disorders. CSF levels of amino acids were obtained by
      isocratic HPLC with electrochemical detection after precolumn derivatization. The
      results obtained indicate that the correlations between assay compounds alter,
      absolute amounts of their content being unchanged.

PMID- 9229860
TI  - [Role of calcium ions in the mechanism of action of acetylcholine on energy
      metabolism in rat liver mitochondria].
AB  - It is shown that administration of acetylcholine to animals (50 micrograms per
      100 g of body weight) leads to the activation of respiration and oxidative
      phosphorylation in the rat liver mitochondria under oxidation of alpha
      ketoglutarate; this effect depends on the concentration of calcium ions in the
      incubation medium of mitochondria. The rate of ADP-stimulated respiration of
      mitochondria of experimental animals reaches its maximum level under lower
      concentrations of Ca2+ than in the control animals. The results of investigation
      of dependence of acetyl choline effect on respiration of mitochondria on the
      concentration of alpha-ketoglutarate in calcium and calcium-free incubation
      medium have shown that the half-maximum effect of acetylcholine is observed in
      calcium medium at lower concentration of the substrate than in calcium-free
      medium. The latter indicates to the increase of affinity of alpha-ketoglutarate
      dehydrogenase to alpha-ketoglutarate under these conditions. It is found out that
      acetylcholine (1.10(-8) M) increases the rate of ADP- and Ca(2+)-stimulated
      respiration of mitochondria of isolated perfused rat liver, while mutual effect
      of verapamyl and niphedipin removes this effect.

PMID- 9229862
TI  - [Method of determining factor IX activity].
AB  - Modification of the method for factor IX activity determination was proposed. A
      mixture of chicken plasma and human plasma was used as factor IX-deficient
      substrate plasma. Moreover determinations were performed in the lack of kaolin
      activator of factor XII. This allowed simplifying the assay performance. The
      described modification may be used to determine factor IX activity in its
      concentrates with the aim of diagnosis of haemophilia B and control of the
      disease treatment.

PMID- 9229861
TI  - [Effect of thyroxine on synthesis of ceramide, sphingomyelin and
      phosphatidylcholine in rat hepatocytes].
AB  - The aim of the study was to investigate the role of thyroxine in the regulation
      of [14C] palmitic acid incorporation into ceramide, sphingomyelin and
      phosphatidylcholine of hepatocytes isolated from 90-day old rats liver. It was
      found that in intact cells the label [14C] incorporation was more pronounced for
      ceramide and phosphatidylcholine. It has been determined that thyroxine activates
      the sphingolipids synthesis. However, the phosphatidylcholine acylation increases
      under hormone action only during the first 5 min of hepatocyte incubation and
      decreases during the following period of incubation.

PMID- 9229863
TI  - [Average length of life and health status of Danes towards the year of 2000].

PMID- 9229864
TI  - [Is alcohol poisonous for the liver?].

PMID- 9229865
TI  - [Hospital rehabilitation of patients with severe traumatic brain injury. I:
      Current status and organization in Denmark and abroad].
AB  - New in-patient rehabilitation methods for the treatment of patients with severe
      traumatic brain injury have been introduced in recent years. These methods are
      primarily characterized by very early start of rehabilitation, by being
      organized, specialized and intensive, and by a multidisciplinary approach. The
      article gives a general description of the present in-patient rehabilitation in
      Denmark, and outlines the principles of new models introduced internationally. In
      conclusion, the in-patient rehabilitation offered in Denmark to patients with
      severe traumatic brain injury is characterized by a lack in the general planning
      and organization of this service, and by being non-specialized, non-intensive,
      and initiated at a late stage.

PMID- 9229866
TI  - [Hospital rehabilitation of patients with severe brain injuries. II: Prognosis
      and effect of early intensive, specialized rehabilitation].
AB  - This article describes the prognosis of patients with severe traumatic brain
      injury, including patients in long-standing coma and persistent vegetative state,
      and presents the scientific evidence of the effect of organized, specialized,
      multidisciplinary, early and intensive rehabilitation of patients with severe
      traumatic brain injury. It is concluded that the introduction of newly developed
      models for the rehabilitation of patients with severe traumatic brain injury in
      Denmark may lead to a substantial improvement in outcome, and may also be cost
      efficient.

PMID- 9229867
TI  - [Significance of intentional weight loss on health].
AB  - The aim of the present study was critically to review how intentional weight loss
      in overweight and obesity influences mortality. No randomized weight loss
      intervention trial has included mortality as an end-point. However, even minor
      weight loss causes beneficial changes in risk factors for cardiovascular disease,
      whereas the vast majority of observational studies have linked weight loss to
      excess mortality. Most observational studies do not have information on
      intentionality of weight loss and suffer from other methodological limitations
      making inferences from these studies difficult. Given the available observational
      evidence, the possibility that intended weight loss may cause some increased
      mortality cannot be excluded. However, considering the totality of the evidence
      on effects of intended weight loss among overweight and obese subjects, there may
      be other benefits, such as: psycho-social and physical well-being, risk factor
      improvement, decreased morbidity, and in certain high-risk subgroups decreased
      mortality. Treatment of obesity is therefore recommended, particularly in the
      presence of risk factors or complications.

PMID- 9229868
TI  - [Changing life expectancy in the 1980's. Why was Denmark different from Sweden?].
AB  - The aim of the present study was to identify the contribution from specific
      causes of death to the changes in life expectancy at birth in Denmark relative to
      Sweden in different age groups during the 1980s and to compare the difference in
      life expectancy between the two countries in 1990. Mortality data from WHO
      mortality tapes grouped in smaller series of clinically meaningful categories
      were used to calculate the contribution of each of these categories at each ten
      year age group to the difference in life expectancy at birth in each country
      between 1979 and 1990 and between the two countries. During the period from 1979
      to 1990 life expectancy increased in both Denmark and Sweden. However, Sweden
      experienced the greatest increase in life expectancy (more than two years) while
      it increased less than one year in Denmark. In both countries a decrease in
      cardiovascular disease mortality contributed most to the increase in life
      expectancy among males as well as females. Both among males and females the less
      favourable development in Denmark was mainly caused by differences in mortality
      trends related to cardio-vascular diseases, respiratory and non-respiratory
      cancer. Over a short period of time two Nordic countries experienced remarkable,
      but different changes in mortality. These findings suggest that mortality rates
      are sensitive to even minor differences in social and cultural factors across
      countries and over short time periods.

PMID- 9229869
TI  - [Alcohol consumption, S-LDL-cholesterol and risk of ischemic heart disease. 6
      year follow-up in The Copenhagen Male Study].
AB  - A high intake of saturated fat is associated with an increase in serum low
      density lipoprotein cholesterol (LDL) and an increase in risk of ischaemic heart
      disease (IHD). In some parts of France a high intake of fat is not associated
      with increased risk of IHD, an apparent discrepancy named the French paradox. It
      has been suggested, but never tested prospectively, that regular use of alcohol
      might explain this low risk. We investigated the interplay between use of
      alcohol, LDL and risk of IHD in a prospective study controlling for a number of
      relevant confounders including other lipid fraction, including 2,826 males aged
      53-74 years without overt IHD. The incidence of IHD during a six year follow-up
      period was registered. One hundred and seventy-two men (6.1%) had a first IHD
      event. There was an overall inverse association between alcohol intake and risk
      of IHD. The association was highly dependent on LDL. In men with a high LDL (> or
      = 5.25 mmol/l), cumulative incidence rates of IHD were 16.4% for abstainers, 8.7%
      for those who drank 1-21 beverages/week and 4.4% for those who drank 22+. Using
      abstainers as reference, adjusted for confounders, corresponding relative risks
      (95% CI) were 0.4 (0.2-1.0), p < 0.05, and 0.2 (0.1-0.8), p < 0.01. In men with a
      low LDL (< 3.63 mmol/l) use of alcohol was not associated with risk. The
      attributable risk (AR) of IHD among men with LDL > or = 3.63 mmol/l who abstained
      from drinking alcohol was calculated; AR with 95% confidence limits was 43% (10
      64%). To conclude, in middleaged and elderly men the inverse association between
      alcohol consumption and risk of IHD was highly dependent on the level of LDL.
      These results support the suggestion that alcohol intake may at least in part
      explain the French paradox.

PMID- 9229870
TI  - [Puerperal fever. A survey of an epidemic using a case-controlled study].
AB  - Puerperal fever caused by group A streptococci (GAS) is a most serious infection
      deriving from the birth canal after childbirth or caesarian section and is
      manifest by fever and/or local signs of infections. Secundary infections in the
      umbilicus or skin can occur in the newborn child. As approximately 5% of the
      Danish population are carriers of GAS in nose, throat, rectum and/or vagina the
      risk of infection is present especially in childbirth. GAS epidemics in the
      community result in increased risk of hospital-acquired GAS infections. In the
      literature it is recommended to take action and implement preventive strategies
      when two simultaneous cases occur in one department. We describe the course of
      seven GAS infections in six patients (two children) in the same obstetric ward
      over a seven-week period, the elucidation by case-control analysis and the
      implementation of preventive measures. The importance of good hygienic practices
      is highlighted.

PMID- 9229871
TI  - [Synchronous variations in the incidence of temporal arteritis and polymyalgia
      rheumatica in Danish counties. Association with epidemics of Mycoplasma pneumonia
      infection].
AB  - The incidences of temporal arteritis and polymyalgia rheumatica during a twelve
      year period were studied in different regions of Denmark. Data concerning the
      incidences of these diagnoses were obtained from two general hospitals from 1982
      to 1994 and from the National Patient Register of all diagnoses from all
      hospitals in 13 of 16 Danish counties from 1982 til 1993. Data from all temporal
      artery biopsies in two counties were also obtained. Serological epidemiological
      surveillance data concerning infections causing epidemics in Denmark were
      obtained from Statens Serum Institut. Data concerning 10,818 patients from 13
      counties and 2651 temporal artery biopsies from two counties were analysed. The
      incidence rate of temporal arteritis in the population aged 50 years and over was
      20.4 per 100,000 (95% CI 19-23), and that of polymyalgia rheumatica 41.3 per
      100,000 (95% CI 30-67). Significantly higher incidence rates were found in
      locations with a high population density. The incidence rate of histologically
      proven temporal arteritis in two counties was 15.1 per 100,000 > 50 years (95% CI
      11-20). Pronounced quarterly and annual variations of the incidence were found,
      with a clustering in five peaks. These cyclic fluctuations were seen
      simultaneously in several regions. Two periods with an increased incidence of
      temporal arteritis and polymyalgia rheumatica occurred in close relation to
      epidemics of Mycoplasma pneumoniae infection. Two peak incidence rates were
      partly related to epidemics of Parvovirus B19 and one peak to an epidemic of
      Chlamydia pneumoniae. The synchronous variations in the incidences of temporal
      arteritis and polymyalgia rheumatica recorded in several regions of Denmark
      strongly indicate that an environmental infectious factor influences the
      frequencies. The close concurrence with the above-mentioned epidemics suggests
      that temporal arteritis and polymyalgia rheumatica may be triggered by certain
      viral and/or bacterial agents.

PMID- 9229872
TI  - [Neurogenic pain following Palestinian hanging].
AB  - The number of refugees around the world who have fled political or ethnic
      persecution has increased. An increasing proportion of these refugees are
      survivors of torture. Many of these suffer physical as well as psychological
      sequelae to torture. In trying to evaluate the torture claims of the refugees, it
      is important for the physician to learn about types of torture and to look for
      symptoms. After positional torture, in which the victims are suspended by their
      wrists which are tied behind their back (Palestinian hanging), severe lasting
      nerve, ligament, or tendon damage is seen. In this paper we present two cases of
      brachial plexus injury. Only sensory nerves were affected causing a neurogenic
      pain condition including dysaesthesia and neuralgia.

PMID- 9229873
TI  - [Lowered number of CD4+cekks--reduced influx or increased loss?].

PMID- 9229874
TI  - [Percutaneous dilatation tracheostomy].

PMID- 9229875
TI  - [Diagnostic invasive examination in primary lung cancer].

PMID- 9229876
TI  - [Over-the-counter slimming products--2].

PMID- 9229877
TI  - [Growth hormone and Creutzfeldt-Jakob disease].

PMID- 9229879
TI  - [New cytogenetic examination methods].

PMID- 9229878
TI  - [Indomethacin reduces cerebral blood flow and the intracranial pressure].

PMID- 9229880
TI  - [The human hematopoietic stem cell biology and clinical use].

PMID- 9229881
TI  - [Cerebral blood flow and indomethacin. The effect of different doses administered
      as continuous intravenous infusions or as suppositories in healthy adults].
AB  - Administration of indomethacin may aid treatment of intracranial hypertension,
      and the present study was conducted to determine the optimal dose. In healthy
      volunteers, cerebral blood flow (CBF) has been shown to decrease considerably
      after a bolus dose of indomethacin, 0.4 mg/kg, followed by continuous infusion,
      0.4 mg/kg/h. This decrease was sustained for 6 h without any evidence of
      adaptation. In a randomized study in healthy volunteers, indomethacin, 0.1, 0.2
      and 0.3 mg/kg, was given as bolus, followed by continuous infusion of 0.1, 0.2
      and 0.3 mg/kg/h. CBF decreased from normal levels (52-74 ml/100 mg/min) to 38-51
      ml/100 g/min. There were no differences among the three groups in CBF reduction,
      and the reduction was sustained during the 6-h infusion period. Rectal
      application of 100 mg indomethacin was found to reduce CBF from normal levels (54
      74 ml/100 mg/min) to 33-48 ml/100 mg/min. These low levels were only sustained
      for 2 h, and values returned to normal over the next 6 h. We observed no rebound
      phenomenon 2 h after stopping the infusion and no rebound after 100 mg of
      rectally applied indomethacin. Since a dose as low as 0.1 mg/kg/h is effective,
      it is possible to treat most patient in a 24-h schedule without going over
      maximum recommended doses.

PMID- 9229883
TI  - [Prolonged sick-leave: the role of general practitioner].
AB  - The aim was to study why long sick leave benefit cases had taken a long time with
      special focus on the communication between the general practitioner and the
      social service department. An explorative study was made of the development and
      communication in 27 consecutive lengthy sick leave cases that had lasted more
      than 13 weeks, that were discussed at three audit panels with participation of
      the social worker/officer in charge, the general practitioner and the
      representatives from the local hospital. The study took place in Aarhus County in
      1994. The results were that many of the same problems were found in various
      cases, such as insufficient certificates, inappropriate use of benefit
      certificates, waiting times for examinations, treatment and especially
      rehabilitation. In the more complicated cases, of which there were many, a
      coordinating person would have helped matters. The GP's were willing to take on
      this role. The main reasons for lengthy benefit cases were that the illness was
      medically complicated and of a long duration.

PMID- 9229882
TI  - [Effect of indomethacin on the intracranial pressure].
AB  - Twenty patients subjected to craniotomy for supratentorial cerebral tumours were
      anaesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2
      level averaging 4.8 kPa was achieved. The patients were randomized to intravenous
      indomethacin 50 mg or placebo administrated after exposure of the dura. A
      significant decrease in intracranial pressure from 6.5 to 1.5 mmHg (medians) was
      found after indomethacin administration. This decrease was caused by a
      significant decrease in cerebral blood flow associated with a significant
      increase in the arterio-venous oxygen difference. Indomethacin did not affect
      cerebral oxygen uptake, arteriovenous difference in lactate or the lactate/oxygen
      index, suggesting that indomethacin did not provoke global cerebral ischaemia. In
      the indomethacin group, dura was sufficiently relaxed in eight of nine patients,
      and dura was opened without the occurrence of cerebral swelling. In the placebo
      group, mannitol supplemented with hypocapnia was applied in five patients. These
      findings suggest that perioperative treatment with indomethacin is an excellent
      treatment of intracranial hypertension during normocapnic isoflurane anaesthesia
      for craniotomy.

PMID- 9229884
TI  - [The impact of postal invitations and user fee on influenza vaccination among the
      elderly. A randomized controlled trial in general practice].
AB  - Influenza epidemics are accompanied by considerable excess morbidity and
      mortality especially among the elderly and the chronically ill. In the influenza
      season 1995 a controlled, randomized trial was carried out to examine the impact
      of postal invitations and user fee on influenza vaccination rates. Five hundred
      and eighty-five patients aged 65 years or older participated. They were all
      recognized by their general practitioner (GP) to be in the risk group to whom
      influenza vaccination is recommended. One third were invited to free influenza
      vaccination. Another third received postal invitations to influenza vaccination
      paying the usual fee ($40-$60 US). The last third served as a control group,
      being vaccinated on their own request and paying the usual fee. In the control
      group 25% (19-31%, 95% confidence interval) of the patients were vaccinated,
      compared to 49% (42-56%) in the group which received a postal reminder and paid
      the usual fee, and 72% (65-78%) in the group invited to be vaccinated free of
      charge.

PMID- 9229885
TI  - ["Blue rubber bleb nevus syndrome"--or Bean's syndrome].
AB  - We describe a case of the blue rubber bleb naevus syndrome, an uncommon systemic
      disorder characterized by multiple bluish haemangiomas of the skin and
      gastrointestinal tract. The syndrome is commonly associated with iron deficiency
      anaemia due to gastrointestinal bleeding. The syndrome is likely to be caused by
      a gene mapping to chromosome 9p and showing autosomal dominant inheritance. This
      is the first Danish report of this unusual disease. We hope that this case will
      heighten the awareness of this condition, because early recognition is essential
      for appropriate medical intervention and genetic counselling.

PMID- 9229886
TI  - [Xenotransplantation--research progress and new problems].

PMID- 9229887
TI  - [District psychiatry].

PMID- 9229888
TI  - [Benign congenital hypotonia].

PMID- 9229889
TI  - [Intra-abdominal undescended testis with seminoma].

PMID- 9229890
TI  - [The focus on the patient].

PMID- 9229891
TI  - [Physical activity and cancer].

PMID- 9229892
TI  - [Medical treatment of cancer].

PMID- 9229893
TI  - [Guidelines for treatment of bronchial asthma in children. Dansk Paediatrisk
      Selkabs Astma- og Allergiudvalg].

PMID- 9229894
TI  - [Combined radiotherapy of uveal melanoma].
AB  - Fifteen patients with uveal melanoma were exposed to combined radiotherapy:
      transscleral exposure of melanoma using a ruthenium ophthalmoapplicator and
      intracorporeal administration of 59Fe. Radiation reaction of the tumor was
      potentiated by combined exposure.

PMID- 9229895
TI  - [Experimental therapy of perforating wounds of cornea with adhelon].
AB  - The efficacy of Adhelon, a new stimulator of repair regeneration belonging to the
      group of adhesion factors, was experimentally assessed in the treatment of ocular
      injuries on a model of perforating untreated wound of the cornea. Clinical and
      histologic studies in two groups of rabbits persuasively demonstrated the benign
      effect of adhelon on the course of wound process: the period of inflammatory
      reaction shortened, infectious complications were prevented, the wound edges
      closed sooner, epithelialization and reconstruction of newly formed cicatricial
      tissue was accelerated. Application of adhelon led to the formation of more
      delicate, compact, and vessel-free cicatrices and accelerated the repair
      regeneration of the wounded cornea.

PMID- 9229896
TI  - [Structural and functional disorders of transcapillary metabolism if retina in
      patients with diabetic retinopathy].
AB  - Transcapillary metabolism of the retina and effects of triglycerides on the
      transcapillary function of the retina in diabetes mellitus were examined in 79
      patients (mean age 45.4 +/- 3 years) with various stages of diabetic retinopathy
      (DR) by fluorometry of the vitreous body. The filtration in the blood-retina
      direction was 1.2-1.3 times higher than in the control as early as during the
      functional and preclinical stages of DR, and the coefficient of fluorescein
      withdrawal from the vitreous body was 4.5 to 6.2% decreased. As DR progressed,
      the permeability of the blood-retinal barrier in the blood-retina direction
      increased and the discharge from the retina to the blood was decelerated, which
      was confirmed by a progressive prolongation of diffusion of 0.1 ml of 1%
      fluorescein solution injected subconjunctivally: from 1.3 +/- 0.2 and 1.4 +/- 0.5
      h in the functional and preclinical stages, respectively, to 2.7 +/- 0.3 h in the
      proliferative stage of DR versus 1.05 +/- 0.01 h in the control. The level of
      serum triglycerides and coefficients of fluorescein entry in and withdrawal from
      the vitreous body, time of papule diffusion, and vascular changes in the
      microcirculatory vessels reliably correlated.

PMID- 9229897
TI  - [Clinical and laboratory assessment of therapeutic efficacy of maxaquin in
      treatment of chlamydial conjunctivitis].
AB  - Maxaquin (lomefloxacin), a new fluoroquinolone antibiotic, was used in combined
      therapy of chlamydial conjunctivitis. The results of treatment of 72 patients
      were assessed by the clinical manifestations and the laboratory time course of
      Chlamydia trachomatis antigen in smears from the conjunctiva, detected by enzyme
      immunoassay. Clinical and laboratory findings proved the high efficacy of the
      drug and its advantages over traditional therapy and other fluoroquinolones.

PMID- 9229898
TI  - [Therapy of chronic allergic conjunctivitis with sodium cromoglycate (lecrolin)].
AB  - The efficacy of lecrolin (2% sodium cromoglycate) eye drops was assessed in 22
      patients with allergic conjunctivitis. Positive effect was attained in all the
      patients on day 4.0 +/- 1.2. Signs of the disease exacerbation completely
      disappeared in 68% of patients in 8.3 +/- 2.4 days. No side effects of any type
      were observed for a month of using lecrolin eye drops.

PMID- 9229899
TI  - [Status of vision organ in children who were born after extracorporeal
      fertilization].
AB  - The status of the organ of vision was assessed in 11 infants born after
      extracorporeal fertilization and transplantation of the embryo with due
      consideration for the general somatic status. The eyes were normal in 5 of the
      examinees. In the rest 6 visual disorders were found. Four of these were
      absolutely blind because of developmental defects and brain hypoxia.

PMID- 9229900
TI  - [A new method for accommodation training].
AB  - A new method for accommodation training making use of a computer is proposed. A
      specially generated dynamic grid of concentric rings serves the stimulus. Changes
      of the accommodation parameters (the nearest and farthest points of clear vision)
      were examined in 11 display users aged 30 to 50 during a training session and in
      the course of 15 sessions. The training improved the accommodation volume by an
      average of 0.9 diopters at the expense of approximating the nearest and
      withdrawing the farthest clear vision points. In 4 subjects anisoaccommodation
      disappeared almost completely. The proposed method may be used to normalize the
      accommodation of display users.

PMID- 9229901
TI  - [Functional topography of the on and off channels of retinal cone system in
      diagnosis of initial glaucoma].
AB  - A new method-achromatic static campymetry-was used for the early diagnosis of
      visual function disorders in glaucoma. It was realized through IBM personal
      computer in the DOS system with SVGA monitor. The method permits examination of
      the functional topography of the on and off channels of the retinal cone system,
      in other words, it detects the early disorders of contrast sensitivity in each
      site of the visual field. Achromatic static campymetry revealed changes in 100%
      of patients with the initial primary open-angle glaucoma in whom the traditional
      static perimetry using Perimat 206 showed no disorders of the central and
      paracentral visual field in the presence of normal ophthalmic tone.

PMID- 9229902
TI  - [Surgical treatment of retinal detachment with multiple, giant and post
      equatorial ruptures].
AB  - A method for surgical treatment of grave detachment of the retina with multiple,
      giant, and postequatorial ruptures has been developed. The method consists in
      combined extrascleral filling making use of bichannel silicon explants. A total
      of 78 patients (78 eyes) were operated on. For control the results of 30
      interventions on 30 eyes (30 patients) with similar injuries have been analyzed;
      in this group traditional methods of combined filling with standard silicon
      explants were used. The patients were followed up for up to 7 years. In the main
      group adherence of the retina was observed in 71.8% of cases in remote periods
      and in 82% after repeated surgery (relapses of retinal detachment occurred in
      15.4% of cases). In controls complete adherence was attained in 60% of cases and
      in 76.7% of those operated on repeatedly (relapses occurred in 23.3%). The
      developed models of bichannel silicon explants are simpler and more effective
      than the traditional methods.

PMID- 9229903
TI  - [Study of antibodies to DNA in patients with bilateral and unilateral endogenous
      uveitis].
AB  - The study was aimed at elucidating the contribution of autoimmune factors to the
      development of bilateral uveitis in children and adults. Sera of 59 children
      (aged 3 to 15) and 34 adults (aged 18 to 60) with unilateral and bilateral
      endogenous uveitis were tested for antibodies to DNA in ELISA. In children aged 3
      to 10 years with bilateral uveitis antibodies to n-DNA were detected more often
      than in those with unilateral involvement. This difference was most expressed
      during the active stage of the disease (p < 0.02). In adult patients the results
      were the contrary. Antibodies to d-DNA were more often found in subjects with
      unilateral uveitis (p < 0.05). Accumulation of anti-DNA antibodies in children
      may be an early sign of systemic immunity disorders, conducive to augmentation of
      ophthalmopathy and to the development of a bilateral process. A lower incidence
      of anti-DNA antibodies in adult patients with bilateral uveitis is probably due
      to the formation of specific circulating immune complexes but not to
      normalization of immunity. These findings permit us to hypothesize that DNA
      autoimmunization is one pathogenetic factor of bilateral development of uveitis.

PMID- 9229904
TI  - [Programmed complex for automated prophylactic check-ups of chronic outpatients.
      Communication 1. Tasks and fundamentals].
AB  - The authors present the fundamentals of making outpatient computer case histories
      for prophylactic check-ups of chronic outpatients with ocular diseases. They
      validate the necessity of creating mononosological versions of computer histories
      which should not only describe the underlying diseases in detail, but reflect any
      concomitant ocular disease as well. The basic criteria formulated by the authors
      helped create a computer history of a modulus type, which may be easily mastered
      by physicians within just 2-3 hours and be adapted to research of this or that
      patient population. The authors emphasize the importance of creating and wide use
      of software in everyday practical medicine.

PMID- 9229905
TI  - [Use of modified standard intraocular lenses in nonstandard situations].

PMID- 9229906
TI  - [Perikom, a static automated perigraph, some aspects of prospective
      standardization of perimetric studies].
AB  - Discusses the functional and operation potentialities of a modern static
      automated perigraph PERIKOM intended for investigating the visual field and
      detecting scotomas of different severity. Presents the basic aspects of
      standardization of perimetric studies in medical institutions of different
      levels.

PMID- 9229907
TI  - [Quantum therapy in ophthalmology: therapy of progressive myopia by ASO devices].
AB  - Progressive myopia was treated by a novel method: quantum ophthalmotherapy.
      Highly effective drug-free treatment is based on the biorhythmical exposure of
      the organ of vision to low-intensive light at different wavelengths. The new
      method helps arrest the progress of myopia, restore the accommodation volume, and
      improve the vision acuity in at least 95% of patients. High efficacy and absence
      of complications confirmed by numerous cases recommend quantum ophthalmotherapy
      with ASO devices for the treatment of progressive myopia.

PMID- 9229908
TI  - [Binocular vision and its role in car driving].

PMID- 9229909
TI  - [Immunohemostatic mechanisms in the development of primary open-angle glaucoma].

PMID- 9229910
TI  - [Diplopia of muscular origin. Etiology, diagnosis and treatment].

PMID- 9229911
TI  - [Some aspects of endocapsular microsurgery in extracapsular cataract extraction].
AB  - Discusses the advantages of preparing the lens sac like an envelope for
      extracapsular cataract extraction with implantation of intraocular lens into the
      lens sac. Aspiration-irrigation evacuation of the lenticular mass from the
      equatorial zone of the lens sac is the cardinal moment in endocapsular
      microsurgery. The authors recommend a common glass syringe with a modified piston
      for evacuating the lenticular mass. The parameters of the piston groove for the
      tightening silicon ring pad are changed, which appreciably improves the
      aspiration characteristics of the syringe and permits effectively and rapidly
      clear the lens sac "envelope" using just 5-10 ml of irrigation solution.

PMID- 9229912
TI  - [Results of direct revascularization of choroid: an experimental study].
AB  - The morphology of histological slices of tissue at the site of direct
      revascularization of the choroid was assessed in various periods (15 days, 1, 3,
      and 6 months) after surgery. The surgical method was as follows: a collagen
      hemostatic sponge, a strip of subconjunctival tissue, and tissue of the external
      rectal muscle were put onto an exposed 4 x 4 mm site of the choroid and closed
      with an episcleral flap fixed with nodular sutures without pulling. Experiments
      were carried out on 13 rabbits (26 eyes). Direct revascularization of the choroid
      was performed in all animals. The animals were sacrificed by air embolism 15
      days, 1, 3, and 6 months after surgery. Vascular filling was carried out. The
      eyes were enucleated, paraffin slices were prepared from tissues at the site of
      operation, and the slices were stained with hematoxylin-eosin, tholuidine blue,
      and after Van Gieson. After direct revascularization of the choroid with
      episcleral, muscular, and subconjunctival tissue and collagen sponge numerous
      full-value vascular formations are seen at the site of the intervention as early
      as 3 months after surgery; these vascular formations connect the extraorbital
      tissues rich in vessels with the vascular coating; the number of newly formed
      vessels increases by 6 months postoperation. The results of experiments give good
      grounds for clinical use of the method.

PMID- 9229913
TI  - [Clinical significance of positional nystagmus].
AB  - Clinical and otoneurological examinations were carried out during 35 years in
      1176 patients with various vestibular disorders. Positional nystagmus (PN) was
      found in 478 patients (40.4%). Horizontal-rotatory or rotatory PN was reported in
      the inner ear disorders; bilateral, horizontal, vertical, diagonal and multiple
      PN occurred only in disturbances of the central nervous system. It was found that
      PN and spontaneous nystagmus (SN) are the signs of different phases of the same
      process; the appearance of the PN after SN in the labyrinthine lesions is the
      symptom of partial compensation of the vestibular function. The examination of
      the PN is important to widen potentialities of the neuro-otological diagnosis
      especially in out patient clinic.

PMID- 9229914
TI  - [Otoneurological symptoms and their changes after removal of pineal tumors].
AB  - The authors analyze otoneurological symptoms in 120 patients with pineal tumors.
      A marked cochleovestibular syndrome was found characterized by bilateral
      neurosensory hypoacusis with vocal-tonal dissociation, head noises, vertigo,
      multiple spontaneous nystagmus including a converging one, impaired optokinetic
      nystagmus, enhanced vestibulovegetative reactions. 39 cases are reported with
      pineal tumors removed microsurgically. Otoneurological symptoms were followed up
      in 32 patients early after surgery (within 20 postoperative days) and in 6
      patients 1 to 5 years after radiotherapy. As evident from otoneurological
      examination, electronystagmography, tonal and speech audiometry, positive
      postoperative changes in auditory and vestibular functions occurred in most of
      the patients. The response persisted long in 5 patients.

PMID- 9229915
TI  - [Early diagnosis of neurosensory component in various forms of conductive hearing
      loss].
AB  - Audiological examination including routine methods, tonal threshold audiometry
      (10000-20000 Hz frequency range), noise resistance of the acoustic analyzer in
      contralateral masking with noises of different intensity has been made to
      identify early subclinical neurosensory hypoacusis in 96 patients with acute and
      chronic inflammation of the middle ear aged 17-75 years. 140 subjects with normal
      hearing served control. The findings show the ability of such tests to assess
      noise resistance of the acoustic analyzer and tonal threshold audiometry in wide
      range of frequencies to detect latent neurosensory hypoacusis which is
      correctable if discovered early.

PMID- 9229916
TI  - [Criteria of the evaluation of tubal function in patients with secretory otitis
      media].
AB  - Tubular function was assessed in patients with secretory otitis media before and
      after surgery (an original version of anterior tympanostomy). Preoperative
      tubular function was measured by impedance tympanometry. After tympanostoma was
      placed the acoustic tube was subjected to direct manometry. Perioperative
      measurements were made for tube patency for liquid (hydrocortisone). The tests of
      pressure adjustment implied routine spirit manometry and updated impedancemetry.
      Technical specifications of modern impedance meters met the criteria of clinical
      fitness for post-tympanostomy patients. The criteria of assessment and
      correlating quantitative values of the draining and ventilation capacities of the
      acoustic tube were determined. This was the basis for an original classification
      of tubular function grades. It was established that in secretory otitis media
      drainage dysfunction of the acoustic tube was registered in two thirds of the
      patients (66%), ventilatory dysfunction occurred in 100% of patients. There was a
      correlation between these functions. This fact was used for design of a simple
      screening variant of ear manometry i.e. registration of the threshold of acoustic
      tube passive opening. Screening manometry is convenient for following up
      postoperative changes in the tubular function and defining duration of carrying
      tympanostomy in secretory otitis.

PMID- 9229917
TI  - [Controlled irrigation using sinus catheter IaMIK-5 in the treatment of chronic
      sinusitis].
AB  - A new modification of sinus-catheter RMNK-5 is proposed enabling simultaneous
      irrigation of the nasal cavity and evacuation of the discharge from the paranasal
      sinuses. Details of the technique are provided. A positive effect consisting in
      attenuation of the inflammation, prolongation of the remission improvement of
      life quality is illustrated in the analysis of 6 cases.

PMID- 9229918
TI  - [Experimental study of biological tissue permeability to Nd-YAG laser irradiation
      with wave length 1.06 and 1.32 mm].
AB  - The author studied penetration of YAG-Nd laser radiation (1.06 and 1.32 mm)
      through some biological tissue. The least penetration of the laser rays occurred
      in the bone and cartilage tissue. Maximal difference in the penetration rate was
      recorded in more transparent for this radiation media - blood agar and nasal
      polyps. The above methodological approach and its results may be used for
      estimation of the energy needed for reaching different biotissue layers in remote
      and contact exposure to YAG-Nd laser.

PMID- 9229919
TI  - [100th anniversary of the Moscow Scientific-Practical Society of
      Otorhinolaryngology].

PMID- 9229920
TI  - [Local use of polymer-based cytostatic agents in surgical treatment of patients
      with laryngeal cancer].
AB  - To improve the outcomes of surgical or combined treatment of patients with
      laryngeal cancer stage III-IV in terms of preventing the recurrences and
      metastases, the authors placed biocompatible polymer material saturated with
      cytostatic in the operative wound in the end of the surgical intervention. The
      response assessed in 107 patients with laryngeal cancer treated with prospidin on
      polymer film (20 cases) versus 87 prospidin-untreated controls was more positive
      in the test group (5-year survival was higher).

PMID- 9229921
TI  - [Treatment of children with congenital diseases of the larynx and trachea].
AB  - +33 cases of vascular tumors, 15 of congenital membranes, 12 of papillomatosis, 5
      of cysts, 12 of abnormal laryngeal cartilages, 3 of tracheomalacia, 9 of stridor,
      1 of fibrous polyp and 1 of mucous membrane folding in the interarytenoid region
      are reported. Operative interventions primarily endoscopic laser surgery were
      performed in children with congenital vascular tumors, membranes, cysts. Removal
      of papillomas in congenital papillomatosis conducted with the use of micro
      instruments and CO2-laser was combined with immunomodulation. Children with
      laryngeal cartilage anomalies, tracheomalacia and stridor were subjected to
      prolonged nasotracheal intubation of even tracheotomy only in case of severe
      respiratory failure..

PMID- 9229922
TI  - [Analysis of the pathological process in chronic otitis media: surgical tactics].
AB  - The outcomes of 200 radical operations for otitis media purulenta (OMP) have been
      summarized for 11 years (1985-1995). The analysis of the cases enabled prognosis
      of OMP complications. It is concluded that in epitympanitis surgery should be
      made as early as possible, each case of chronic purulent epitympanitis is a
      threat not only for acoustic and vestibular function but also for the patient'
      life.

PMID- 9229923
TI  - [Giant cholesteatoma of the middle ear destroying the pyramid and exposing the
      cranial fossa].

PMID- 9229924
TI  - [A case of accessory lobe of the thyroid gland located in the area of upper
      esophageal narrowing].

PMID- 9229925
TI  - [A rare foreign body of the tympanic cavity (acryl) necessitating surgical
      intervention in the middle ear].

PMID- 9229926
TI  - [Wegener's granulomatosis: a case report].

PMID- 9229927
TI  - [From the history of the treatment of nasal polyps].

PMID- 9229928
TI  - Experimental measles. II. Infection and immunity in the rhesus macaque.
AB  - Measles infection and the host immune response to measles virus was compared
      using naive and immunized rhesus monkeys. The monkeys were experimentally
      challenged with a wild-type strain of measles virus inoculated intranasally.
      After pathogenic virus challenge, measles virus was detected in mononuclear cells
      of peripheral blood, lymph node, and spleen in naive monkeys and viremia peaked
      on Day 7. However, only one of five vaccinated monkeys had a lower virus titer in
      peripheral blood mononuclear cells at one time point after challenge. No virus
      was detected in the lymphoid tissues from an immunized monkeys that was
      euthanized on Day 7 of infection. Measles-specific IgM, IgG, neutralizing
      antibody, and cytotoxic T lymphocytes were detected in vaccinated monkeys before
      challenge, but antibody titers were significantly lower in immunized monkeys than
      in naive monkey after challenge. Measles-specific IgG antibody and cytotoxic T
      cell responses were still detected more than 1 year after vaccination or
      infection. This animal model is useful for the further study of measles
      pathogenesis, immunosuppression, and immunologic memories.

PMID- 9229929
TI  - [Post-gunshot wound lesions of the peripheral nerves which may be prevented with
      adequate primary surgical wound care].
AB  - The retrospective study includes 24 wounded persons with iatrogenic peripheral
      nerve lesion and 94 wounded whose neural damage occurred due to peripheral nerve
      engagement in scar tissue after main artery reconstruction, missile bone fracture
      or after soft tissues defects covering by Tiersch transplants. The authors
      analyzed frequency and localization of these lesions, intraoperative findings,
      applied operative procedures and clinical findings during preoperative follow-up.
      It is recommended to create the new bad for exposed peripheral nerve from
      adjacent muscles as part of primary surgical wound treatment. This procedure
      eliminates the risk of subsequent epineural scar formation in all situations that
      have been described (soft tissue defects, artery reconstruction and bone
      fracture) and makes the later operations on peripheral nerves unnecessary.

PMID- 9229930
TI  - [Adaptation problems of soldiers to the military environment].
AB  - Sixty six conscripts were examined during the first 30 days of military service,
      in the period of adaptation to the military environment. Out of total number of
      the examined soldiers, 83.33% of them enlisted with previous problems from the
      civilian life. Two thirds of the examined soldiers experience difficulties
      enduring the conditions of the soldiers' life, and 2/3 of the examined soldiers
      encountered problems in interpersonal relations in the unit. The most frequent
      diagnosis was emotionally immature personality (39.39%), then intellectual
      deficiency (24.14%). 43.94% of soldiers were referred to the Military Medical
      Board with the recommendation of 'temporary disability' and 28.79% with the
      recommendation of 'permanent disability' for the military service, while 21.21%
      of soldiers were returned to their units are 'capable' for the military service.

PMID- 9229931
TI  - [Care of injured and ill patients in combat areas in the former Yugoslavia 1991
      1992].
AB  - Large number of military and civilian physicians took part in war on the
      territory of former Yugoslavia during 1991/1992, managing the medical service or
      in medical units of Yugoslav Peoples' Army and civilian health institutions.
      Their vast war experiences were presented in their reports and numerous papers
      published in proceedings of congresses and meetings, held in the period from 1992
      till today. This is an attempt to systematize those experiences and to draw out
      some conclusions significant for the further development of doctrinaire approach
      to the organization and functioning of the medical service of the Army of
      Yugoslavia at war.

PMID- 9229932
TI  - [Ear acupuncture has a hypotonic effect on the gastrointestinal tract].
AB  - The effect of auricular acupuncture (AAP) on the motility and tone of
      gastrointestinal tract was investigated in 60 patients, by comparison of the
      width of corpus and antrum of the stomach, as well as duodenum before and after
      the application of AAP. The obtained results showed that the effects of AAP and
      usual drugs were equal. The fact that AAP was applied without any side effects
      and contraindications pointed to the possibility of its wider application in
      clinical practice.

PMID- 9229933
TI  - [Repair of a severed nerve with denatured muscle graft--preliminary results of a
      new surgical technic].
AB  - In Neurosurgical Clinic of Military Medical Academy prospective study about the
      use of denatured muscle graft in nerve repair is in progress, based on numerous
      experimental and sporadic clinical literature data. The first, experimental part
      of the investigation is directed to operative technique details and also to find
      out the manner and duration of muscle denaturation which provide ideal conditions
      for regenerating axons sprouting. It is concluded that greater pectoral muscle
      have to be muscle graft donor for nerve defects shorter than 6 cm, and sartorius
      muscle for those longer than 6 cm. Denaturation for 30 seconds in liquid nitrogen
      and after that in distilled water for 3 minutes results in micromorphological
      status in muscle graft which is optimal for axonal regeneration. In the second,
      clinical part of the work reparations of missile neurotmesis of radial nerve with
      denatured muscle grafts are performed. Preliminary results 9 months after
      operation are quite comparable with results after sural nerve graft reparation.

PMID- 9229934
TI  - [Definition and classification of unstable angina pectoris].

PMID- 9229935
TI  - [Mechanisms of excitatory neurotoxicity and perspectives in therapy with
      excitatory amino acid antagonists].

PMID- 9229936
TI  - [Delayed "re-do" reconstruction of the femoral vein with a panel-graft--case
      report].

PMID- 9229937
TI  - [The cerebrovascular circulation steal syndrome].

PMID- 9229938
TI  - [Multiple and recurrent infection in a child with the rat tapeworm, Hymenolepis
      diminuta].

PMID- 9229939
TI  - [History of the Department of Gynecologic Diseases at the Academy of Military
      Medicine in Belgrade].

PMID- 9229940
TI  - [Carbon dioxide inhibits the generation of active forms of oxygen in human and
      animal cells and the significance of the phenomenon in biology and medicine].
AB  - Carbon dioxide (CO2) influence in generation of active oxygen forms (AOF) in
      human mononuclear cells (blood phagocytes and alveolar macrophages) and animal
      cells (tissue phagocytes, parenchymal and interstitial cells of liver, kidney,
      lung, brain and stomach) was investigated. The AOF generation was examined by the
      methods of chemiluminiscence (CL) using luminol, lucigenin and NBT (nitro blue
      tetrazolium) reaction. It was established that CO2 in concentrations similar to
      those in blood (5.1%, pCO2 37.5 mmHg) and at high concentrations (8.2%, pCO2 60
      mmHg; 20%, pCO2 146 mmHg) showed pronounced inhibitory effect on the AOF
      generation in all the studied cells (usually reducing it 2 to 4 times). Those
      results were obtained not only after the direct contact of isolated cells with
      CO2, but also after the whole body exposure to CO2. Besides, it was established
      that venous blood gas mixture (CO2 - 45 mmHg, +O2 - 39 mmHg, + N2 - 646 mmHg)
      inhibited the AOF generation in cited cells more than the arterial blood gas
      mixture (CO2 - 40 mmHg, + O2 - 95 mmHg, + N2 - 595 mmHg). Carbon dioxide action
      mechanism was developed partially through the inhibition of the OAF generation in
      mitochondria and through deceleration of NADPH oxidative activity. Finally, it
      was established that CO2 led to the better coordination of oxidation and
      phosphorylation and increased the phosphorylation velocity in liver mitochondria.
      The results clearly confirmed the general property of CO2 to inhibit
      significantly the AOF generation in all the cell types. This favors the new
      explanation of the well-known evolutionary paradox: the Earth life and organisms
      preservation when the oxygen, that shows toxic effects on the cells through the
      AOF, occurs in the atmosphere. The results can also be used to explain in a new
      way the vasodilating effect of CO2 and the favorable hypercapnotherapy influence
      on the course of some bronchial asthma forms. The results are probably
      significant for the analysis of important bio-ecological problem, such as the
      increase of CO2 concentration in the atmosphere and its effect on the humans and
      animals.

PMID- 9229941
TI  - [Analysis of the occurrence of degenerative changes in the spinal column in
      military tank personnel in relation their body height].
AB  - The relation of tankers' body height to the level of their spinal column
      degenerative changes, as well as the frequency of painful vertebral syndrome,
      have been examined to note the effect of constrained body position on the onset
      of vertebral syndrome. Fifty examinees, tank commanders, divided into 2 body
      height groups, were included in the study. There were 25 examinees with body
      height up to 1,750 mm in group A and 25 examinees with body height > 1,760 mm in
      group B. The average body height of the studied population was 1,752 mm-1,716 mm
      in group A and 1,788 mm in group B. The investigation established no significant
      difference between studied groups - neither in degenerative changes on spinal
      column frequency, nor in painful vertebral syndrome frequency, which favors the
      conclusion that the total studied population had inappropriate body height for
      tank conditions, and therefore it reacted homogeneously to the tested harmful
      environment.

PMID- 9229942
TI  - [Personal experience in the treatment of tuberculosis in patients in war areas].
AB  - In the four-year period (1991-1995), 96 tuberculosis patients from the war areas
      of former Yugoslavia were treated in the Clinic for Lung Diseases of Military
      Medical Academy, that makes 31% of total number of sick and treated for
      tuberculosis-309 (100%). In group I (patients from war areas) there were 45 cases
      of cavernous pulmonary tuberculosis (47%), 28 bilateral (29%), 16 pleurisy
      (16.7%) and 6 cases of extensive pulmonary tuberculosis (5.1%). Among 213
      patients (100%) from group II (patients from FR Yugoslavia), 81 patients had
      cavernous pulmonary tuberculosis (38%), 49 patients had bilateral (23%), 33
      patients had pleurisy (15.5%) and 6 patients had extensive pulmonary tuberculosis
      (2.8%). In group I the diagnosis was bacteriologically and/or histopathologically
      proved in 94.8% cases: by finding of acid-resistant bacilli in sputum and other
      biological materials in 69 patients (72%), by positive Lowenstein's cultures in
      73 patients (76%) and by histopathological result of tuberculosis inflammation in
      34 patients (35.4%). In group II tuberculosis was bacteriologically and/or
      histopathologically proved in 134 patients (63%) by acid-resistant bacilli in
      sputum and other biological materials, in 141 patient (66%) by positive
      Lowenstein's culture and in 71 patient by positive histopathological results.
      Pulmonary tuberculosis in war areas is characterized by greater frequency of
      severe clinical forms (cavernous, bilateral and extensive) and by high direct
      bacillarity.

PMID- 9229943
TI  - [Endemic nephropathy in the region of Bela Crkva in Banat].
AB  - The village of Kusic is situated 8 km southwestern of Bela Crkva, at the very
      border, separated from Romania by the river Nera. Due to frequent disease
      occurrence in the village Kusic, the pelustration of population was done in 1978
      and 1989, and during the later follow-up, many patients were examined either in
      hospital or in outpatient clinics. The aim was to confirm a suspicion on the
      existence of the focus of endemic nephropathy in the village of Kusic. In 1978
      and 1989 abnormal proteinuria was found in 17.7% and 16.7% examines from the
      village of Kusic, respectively-significantly higher than in surrounding villages:
      Grebenac, Vracev Gaj, Banatska Palanka and Kruscica (p < 0.01). Slow progression
      to the lasser degree of anemia was found in the patients with proteinuria,
      compared to the control group. Eight of 10 regularly dialyzed patients died, and
      in 4 patients urothelial carcinoma was diagnosed. In all of them
      nephroureterectomy was performed, and one patient with advanced disease died 6
      months after surgery. On the basis of cited data, by their comparison and further
      prospective observation of the patients from the village of Kusic, it was
      concluded that the new focus of endemic nephropathy existed in southeastern
      Banat.

PMID- 9229944
TI  - [IgA nephropathy--IgA1 disease].
AB  - The aim of this study was to prove the increased IgA1 production in patients with
      IgA nephropathy compared to the control group of healthy subjects, by
      determination of serum subclasses IgA, IgA1 and IgA2 levels. That with the
      exclusive presence of IgA1 in kidney tissue, justified the assertion that IgAN
      was IgA1 disease. Eighteen patients with IgA nephropathy, 15 male and 3 female,
      average age 17-54 (mean +/- SD = 34.1 +/- 5.18) were included in the prospective
      study. The diagnosis was proved by immunofluorescent assay of bioptic kidney
      material obtained by ultrasonically guided biopsy. The total serum IgA and IgA1
      and IgA2 subclasses levels were determined in the patients and healthy conscripts
      from the control group. The methods of immunonephelometry and radial
      immunodiffusion were used. Increased IgA values were found in 22.75% and of IgA1
      subclass in 38.85% patients. Patients with IgA nephropathy had significantly
      higher IgA1 values (p < 0.01), compared to the control group. There was no
      significant difference in IgA2 subclass levels. Renal function did not
      significantly affect IgA1 and IgA2 subclasses values.

PMID- 9229945
TI  - [Microbiological findings on Vikopres paste after functional impressions of the
      upper jaw].
AB  - The microbiological status and disinfecting effect of Vikopres zinc-oxide eugenol
      paste was investigated after the functional impression was taken. The examinees
      were persons with edentulous maxilla (n = 32). The silicon paste of similar
      viscosity applied in the same persons was used as the control. The samples for
      microbiological tests were taken immediately, 30 minutes later and 3 hours after
      the impression was made. Significantly less samples with positive bacteriological
      findings were found on Vikopres paste, compared to the control one.

PMID- 9229946
TI  - [The significance of physical activity and anthropometric parameters for the
      development of breast cancer].
AB  - The significance of physical activity and some anthropometric parameters (body
      mass, body height, body mass index) in breast cancer genesis was examined in the
      study. Anamnestic study included 106 women with breast cancer and 106 hospital
      controls, age-matched (+/-3 years). The data about risk factors for breast cancer
      genesis were collected by the targeted epidemiological questionnaire. The basic
      statistic parameters (mean, standard error) and t-test were calculated. The
      results indicated that physical activity and body height higher values appeared
      to be protective, while body mass and body mass index higher values could be
      considered as risk factors for breast cancer.

PMID- 9229947
TI  - [The cytoprotective agent amifostine (WR-2721): current clinical use and trends
      in its development].

PMID- 9229948
TI  - [Fleroxacin--a new quinolone antibiotic].

PMID- 9229949
TI  - [Interaction of microorganisms with the host immune system].

PMID- 9229950
TI  - [Suprasellar and pineal germinoma with spinal dissemination].

PMID- 9229951
TI  - [Parinaud's syndrome: causes and pathophysiologic mechanisms in patients].

PMID- 9229952
TI  - [Standards of physical fitness in Yugoslav military personnel].
AB  - With the aim to develop the standards of aerobic capacity as one of the basic
      elements of physical fitness of the military personnel, the authors worked out an
      original method, based on determination of energy requirements for different
      military activities, and on WHO principle for estimation of working capacity.
      According to the data on application of these standards in the group of 176
      officers in the Yugoslav Armed forces, shown in the paper, even 53.4% og the
      officers have the aerobic capacity less than required for the duties they
      perform. Comparing their standards to those used in some other armies, the
      authors point out the validity of the same and an imperative to be introduced
      into Yugoslav Armed forces.

PMID- 9229953
TI  - [Craniocerebral injuries at the Vukovar battlefield].
AB  - In Neurosurgical Clinic of Military Medical Academy 33 wounded persons with
      craniocerebral injuries (CCI) from Vukovar battlefield were treated from
      September 16 to December 3. After the follow-up period of average 48 months the
      outcome of treatment was analyzed compared to the clinical status on admission
      and to the extent of cerebral lesion. All wounded with minor CCI (GCS = 15) and
      majority with mild injuries (GCS = 13-14) had the good outcome, and all the
      wounded with severe injuries (GCS = 3-8) died (p < 0.01). After unilobar
      penetrating CCI the outcome was mostly good, but after multilobar and
      transventricular injuries the outcome was worse or lethal (p < 0.01). Total
      mortality rate was 27.3%. Our conclusion is that bad clinical status on admission
      and more extensive cerebral lesions correlate with worse outcome of treatment of
      war CCI.

PMID- 9229954
TI  - [Radioprotective agents in the decontamination of rats poisoned with
      percutaneously administered mustard gas].
AB  - The efficacy of rat skin decontamination by radioprotective agents AET and
      cystamine were tested. Results were compared to standard decontaminants
      alcoholate, clay and fuller's earth. It was found that all the animals
      decontaminated with standard decontaminants had survived 4 LD50 of poison for 21
      days. All the animals poisoned by 6 LD50 had survived for 1 day except for those
      decontaminated with alcoholate where 50% survived throughout the observation
      period. Alcoholate and clay protected all, and fuller's earth 70% of animals
      poisoned by 12 LD50, but no longer than 24 h. AET and cystamine protected all
      rats from 1.7 LD50 for 3 days, from 1 LD50 for 2 days, and from 2 LD50 for 1 day.
      When higher doses of poison were used (1.7-6.8 LD50) only partial protection was
      achieved. Our results support the conclusion that radioprotective agents could be
      convenient means for improvised decontamination of persons poisoned by sulfur
      mustard, so additional investigations are necessary.

PMID- 9229955
TI  - [Evaluation of the efficacy of electroconvulsive therapy in the treatment of
      delusional, congruently delusional and non-congruently delusional subtypes of
      unipolar affective disorders].
AB  - In this retrospective pilot study we tried to find out whether there were any
      differences in therapeutic response to electroconvulsive therapy in the patients
      with diagnosed unipolar affective disorder due to the presence and type of
      delusions in the clinical course of the disease. The sample consists of 45
      inpatient unipolar depressives, 15 male and 30 female, divided into 3
      experimental groups: nondelusional depressions, depressions with congruent
      delusions and depressions with incongruent delusions. Two variables were used to
      estimate the therapeutic response: number of received ECT treatments and
      proportion of full remissions. Our results showed significant differences between
      all the groups for both variables with the best therapeutic response in the group
      of incongruent delusional depressions and the worst in the group of nondelusional
      depressions.

PMID- 9229956
TI  - [Penicillin resistance in strains of Streptococcus pneumoniae].
AB  - The values of minimal inhibitory concentration (MIC) of penicillin were
      determined using the agar-dilution method for 114 strains of Streptococcus
      pneumoniae isolated during 1994 in the patients treated in hospital and
      outpatient clinics. Diminished susceptibility to penicillin was determined in 50
      (43.8%) strains. High level of penicillin resistance was observed in 12 (10.5%)
      strains. Streptococcus pneumoniae cannot any more be regarded as the agent with
      presumed susceptibility to penicillin, but every isolated strain must be tested.

PMID- 9229957
TI  - [Electromyography recording of the silent period in masseter muscles in persons
      with total dental prostheses with various vertical occlusal dimensions].
AB  - Silent period is reflex pause or period suppressed activity after some kind of
      simulation during or after muscular contraction. In dentistry
      electromyographically registered silent period has important place as method of
      functional diagnosis. The aim of this investigation was to establish duration of
      silent period in both masseter muscles of persons with complete dentures in
      normal increased and decreased occlusal vertical dimensions. Subjects of
      investigation were 4 men and 4 women, average of 65 years. Occlusal vertical
      dimensions were established electromyographically. For every subject tree sets of
      complete dentures were made: with normal, increased and decreased occlusal
      vertical dimension for 4 mm. Silent period was registered by "Medlec" Mystro-MS
      20 apparatus with intramuscular leads. The differences of silent period duration
      were registered among all three vertical dimensions, especially between and
      increased occlusal vertical dimensions.

PMID- 9229958
TI  - [Diagnostic and prognostic significance of oncogenes in pulmonary carcinoma].

PMID- 9229959
TI  - [The significance of specific oligonucleotides in clinical medicine and their use
      in the treatment of patients with infective diseases].

PMID- 9229960
TI  - [Modern therapy of idiopathic nephrotic syndrome].

PMID- 9229961
TI  - [History of the development of surgery of the greater omentum].

PMID- 9229962
TI  - [Fundamentals of computer analysis of bioelectric signals].

PMID- 9229963
TI  - [Case report of herpetiform pemphigus].

PMID- 9229964
TI  - [Results of repair of severed nerves in war injuries].
AB  - The results of surgical treatment of 397 wounded with 482 neurotmeses (64 median,
      97 ulnar, 100 radial, 7 musculocutaneal, 120 peroneal and 94 tibial nerves) were
      analyzed. The treatment outcome was determined 12-36 months postoperatively by
      analyzing the sensorimotor recovery, EMNG status and operated person's attitude
      to the repair outcome. The change of all the four mentioned parameters was graded
      from 0 to 5 points, and the outcome was qualified as poor, moderate, good or
      excellent according to the point sum total. The majority of good and excellent
      results was obtained after radial (85%) and musculocutaneal (100%) nerve repairs
      and the less after peroneal nerve repair (13.3%). Based on the obtained results,
      it was concluded that radial and musculocutaneal neurotmeses should always be
      repaired, disregarding the height of lesion. Repair of high ulnar and peroneal
      lesions was unsuccessful. High lesions of tibial and median nerves should be
      repaired because of the possible recovery of protective sensibility in autonomous
      nerve zone.

PMID- 9229965
TI  - [The Miles-Thompson-Bricker method of total pelvic exenteration in malignant
      tumors of the rectum with urinary bladder infiltration].
AB  - The radical method of surgical treatment of malignant rectal neoplasms, total
      pelvic exenteration by Miles-Thompson-Bricker, was introduced in the Clinic for
      General and Vascular Surgery of Military Medical Academy in October, 1993, 45
      years after the first operation of that kind in the world. This method of
      surgical treatment was indicated in 3% of our patients with malignant neoplasms
      of the distal part of rectum that infiltrated the urinary bladder. The life of
      patients with two stomas though not easy, was prolonged.

PMID- 9229966
TI  - [Serologic diagnosis of Crimean hemorrhagic fever in Kosovo and Metohia].
AB  - In the period June-November 1995, 292 sera from 159 patients and 80 healthy
      persons from Kosovo and Metohia were tested for the presence of antibodies
      against the causative agents of Crimean hemorrhagic fever (CHF) and hemorrhagic
      fever with renal syndrome (HFRS). Diffusion precipitation test in agar gel and
      indirect immunofluorescence assay were used. Specific antibodies against CHF
      virus were found in 6.9% and against HFRS virus in 15.1 patient's sera.
      Antibodies against CHF virus were proved in sera of patients on the fifth day
      from the disease onset at the earliest. No wanted antibodies were found in
      healthy persons' sera. The results of sera testing on antibodies against CHF
      virus were analyzed in detail.

PMID- 9229967
TI  - [Clinico-laboratory characteristics and treatment of patients with trichinosis].
AB  - The severity of clinical features of trichinosis and cardiac involvement
      incidence were examined in the study. The values of eosinophiles, serum enzymes
      and serologic response to T. spiralis were determined in relation to the disease
      severity. Twenty-nine patients, of mean age from 24 to 29 years treated in the
      Clinic in the period from January to April 1995 were presented-7 with severe form
      of trichinosis, 10 with moderately severe and 12 with light. The fever was
      noticed in 93.1% of patients, gastrointestinal disorders in 65.5%, myalgias in
      96.6%, facial edema in 79.3%, cardiac disorders in 31% and rash in 20.7%.
      Positive IIF test result was found in 100% of patients with severe clinical
      features, and only in 58.3% of patients with light clinical features. The
      patients were treated with mebendazole in the dose of 25 mg/kg BM a day during 14
      days. It was concluded that severe trichinosis forms were frequently followed by
      myocardial damage, that severe forms responded faster and better serologically to
      trichinella and those patients should be treated with high mebendazole doses.

PMID- 9229968
TI  - [Percutaneous needle biopsy of the distal part of the choledochal duct].
AB  - The indication for the biopsy was the finding of stenosis of uncertain etiology
      even after the endoscopy and the attempt of endoscopic or brush biopsy. The
      experiences with needle biopsy in 6 patients were presented in the study. The
      biopsy was done with the needles with diameter less than 1 mm (Chiba needle 0.6
      0.95 mm), Otto-cut 0.8 mm and Vacu-cut 0.8 mm. Percutaneous cholangiography that
      was firstly performed, showed the site of stenosis of common bile duct distal
      part and simultaneously the other structures of interest for biopsy performance.
      The needle was guided under radioscopic control in one attempt. In that way, the
      precise diagnosis of pathologic process, which induced the obstruction in the
      early disease stage was made in all six patients. On the basis of cited results,
      the percutaneous needle biopsy was found to be efficient and safe method to
      reveal the type of lesion in this region, if necessary conditions existed.
      Percutaneous needle biopsy is a very valuable method, less invasive and less
      expensive compared to the surgical biopsies and other methods. It demonstrated
      reliable results in our conditions.

PMID- 9229969
TI  - [Clinical and laboratory studies of cholinergic urticaria].
AB  - The clinical and laboratory study of 80 patients (75 males, 5 females) with
      cholinergic urticaria (CHU), treated from 1971 to 1996 is presented. The mean age
      at CHU occurrence was 22.3 years (10-50). The disease lasted at the time of
      examination from 3 months to 14 years, on an average 2 years and 11 months. Among
      30 studied patients, the disease ceased after 1-3 in 5 patients, and it lasted
      from 3 to 24 years, on an average 9 years, in the remaining 25 patients. Exercise
      induced anaphylaxis occurred in 8 patients and simultaneously cold urticaria
      occurred in 7 patients. The increase of histamine level in blood, following the
      exercise and/or heat test was found in 12 examined patients. The higher increase
      was noticed after the exercise, than after the heat test, which was well
      correlated with the severity of clinical features and the duration of skin
      manifestations. Repeated heat and/or cold test, performed at the same day, showed
      the weaker or no reaction at all. The role of the sweat, acetylcholine and
      histamine in CHU occurrence was discussed.

PMID- 9229970
TI  - [Euthanasia].

PMID- 9229971
TI  - [Active mediators in the pathogenesis of septic shock and the importance of their
      neutralization in the treatment of patients].

PMID- 9229972
TI  - [Tardive dyskinesia with special emphasis on tardive dyskinesia caused by
      neuroleptics].

PMID- 9229973
TI  - [The syndrome of disseminated demyelinating disease of the central nervous system
      and chronic inflammatory demyelinating polyradiculoneuropathy].

PMID- 9229975
TI  - The Belgian Association for Cancer Research. Liege, January 25, 1997. Abstracts.

PMID- 9229974
TI  - [A century since the discovery of x-rays--the development of radiology at the
      Academy of Military Medicine].

PMID- 9229976
TI  - Mapping the genes for IgE production and allergy.

PMID- 9229977
TI  - [Ethics in intensive medicine. The practice of medical decision making].

PMID- 9229978
TI  - [Ethics in intensive medicine].
AB  - In more than 30 years of development of intensive care medicine (ICM), our
      specialty has acquired moral and ethical standpoints, although not without public
      pressure and discussions. Special commissions dealing, e.g., with brain death,
      terminal care, ethics of foregoing life-sustaining treatment in the critically
      ill, withholding or withdrawing mechanical ventilation, and other issues have
      been formed in a number of medical societies. International consensus conferences
      have helped to clarify some of the issues. With increasing experience, a
      multitude of ethical problems have arisen in ICM that have to be dealt with, such
      as the issue of quality of life. What is an unworthy life? Are we allowed to make
      judgments for our patients? What is cost-effectiveness in ICM? Other restrictions
      include bed and equipment shortages in the intensive care unit (ICU), the
      necessity for triage--undisputed in catastrophe medicine--and how one should
      proceed in managing elective patients? In situations of limited ICU bed
      availability, sicker patients will be admitted, sparing out patients who are less
      ill for observation and those with poor quality of life and poor prognosis. For
      the future, it will likely be necessary to define the patients who should be
      admitted to an ICU more than those who should not be admitted. An ICU treatment
      entitlement index would be directly proportional to the probability of successful
      outcome and the quality of the remaining life, and would be inversely related to
      costs for achieving success. The ICU outcome with survival, hospital mortality,
      and follow-up of ICU patients is considered. DNR (do not resuscitate), the dying
      patient, terminal care, terminal weaning--DNT (do not treat)--active and passive
      euthanasia, living wills, quality of life, and cost-effectiveness for ICU
      patients are defined. Their application in the ICU will be discussed and problems
      pointed out. Outcome predictions using scores (APACHE III, SAPS II, MPM) have
      been developed based on previous experience, but should only be applied to
      patient groups and for quality assurance in ICUs. The most frequent and difficult
      problem in the ICUs is the vegetative state, which requires an exact diagnosis.
      The differential diagnosis from other comatose states such as coma, brain death,
      and locked-in-syndrome is depicted. The ethics of interrupting life-sustaining
      treatment in critically ill patients have been worked out by a Task Force on
      Ethics of the Society of Critical Care Medicine (1990). A consensus was found
      that the patient may judge to forego therapy; ethically it is then appropriate to
      withhold or withdraw therapy. According to the consensus, withdrawing an already
      initiated treatment should not necessarily be regarded as more problematic than a
      decision not to initiate treatment. In my mind, however, there is a great
      difference between withdrawing or withholding, e.g., ventilation. A dissentive
      opinion by some members of the Task Force stated that hydration and nutrition
      other than high-technology or parenteral nutrition are key components of patient
      care, and should not be equated with medical intervention. The ethical problems
      associated with active euthanasia (physician-assisted suicide or death) as
      practised in the Netherlands are also discussed. In most countries this practice
      seems unacceptable. From 30 years experience in ICM, there are many more ethical
      questions and case reports without clear solutions. Care decisions for single
      patients in unacceptable situations should be made after medical evaluation by
      the intensivist with the medical team and, if possible, by the patient and/or his
      or her surrogate. Legislation and solutions cannot be expected for single
      patients, but ethics committees could be helpful in decision-making.

PMID- 9229979
TI  - [Ethical conflicts during anesthesia. "Do not resuscitate" orders in the
      operating room].
AB  - Patients have the right to make decisions concerning their health care. The right
      to consent to or refuse treatment is based on the ethical principle of autonomy.
      Respecting a patient's autonomy has emerged as one of the leading principle in
      medical ethics in the last years. In the United States, the Patient Self
      Determination Act of 1991 stated that all patients admitted to hospital have to
      be informed about their right to prepare advance directives and to refuse life
      prolonging treatment. Do-not-resuscitate (DNR) orders have been established to
      provide a mechanism for withholding specific resuscitative therapies in the event
      of cardiac arrest. Patients may write DNR orders to express in advance their
      preferences at a time when they are capable of making informed decisions.
      Terminally ill patients may need palliative surgical interventions to relieve
      pain or facilitate care. In patients with DNR orders undergoing anaesthesia and
      surgical procedures, the DNR status in the operating room is increasingly a
      matter of ethical conflict. Anaesthetic care virtually always implies the
      provision of resuscitative measures if necessary. Interventions like intubation,
      mechanical ventilation, or administration of vasoactive drugs may be regarded as
      a part of resuscitative efforts. There is a remarkable lack of consistency in
      policies and practices in hospitals regarding interpretation of DNR orders during
      the perioperative period. Considering policies automatically suspending DNR
      orders prior to anaesthetic care, the American Society of Anesthesiologists (ASA)
      in 1993 introduced "Ethical guidelines for the anesthesia care of patients with
      do not resuscitate orders or other directives that limit treatment". To address a
      patient's right to self-determination in a responsible and ethical way, the ASA
      recommends explicitly discussing with the patient all limitations of therapeutic
      interventions. A list of relevant items that should be considered, like
      defibrillation and chest compression, but also blood product transfusion or the
      administration of antibiotics, has been provided by the ASA. These statements can
      provide some order to an increasing state of the uncertainty, but guidelines
      might also be regarded as imposing restrictions that compromise the
      anaesthesiologist's autonomy. I believe that defining accepted and refused
      interventions in advance is not an appropriate approach to DNR orders during
      anaesthesia and surgery, as it will be difficult to find a definition of what
      constitutes resuscitation in this context. Communication with the patient and
      exchange of information are essential factors promoting ethical decisions.
      Knowing the individual patient's preferences and fears, a more suitable approach
      seems to be the perioperative suspension of the DNR order for a limited period of
      time, with the assurance that therapeutic procedures instituted during surgery
      will be discontinued postoperatively in reconsideration of the DNR order and if
      the underlying disease process turns out to be non-reversible.

PMID- 9229980
TI  - [Ethical conflicts in emergency medicine].
AB  - OBJECTIVE: Thirty years ago, cardiopulmonary resuscitation (CPR) was primarily
      developed for otherwise healthy individuals who experienced sudden cardiac
      arrest. Today, CPR is widely viewed as an emergency procedure that can be
      attempted on any person who undergoes a cessation of cardiorespiratory function.
      Therefore, the appropriateness of CPR has been questioned as a matter of the
      outcome, the patient's preferences, and the cost. The objective of this article
      is to analyse ethical issues in prehospital resuscitation. ARGUMENTS: CPR is
      bound by moral considerations that surround the use of any medical treatment.
      According to Beauchamp and Childress, the hierarchy of justification in
      biomedical ethics consists of ethical theories, principles, rules, and particular
      judgements and actions. The decision to start CPR is based on the medical
      judgement that a person is suffering from circulatory arrest. The decision is
      justified by the moral rule that the victim of a cardiac arrest has the right to
      survive and to receive CPR. Moral rules are more specific to contexts and are
      based on ethical principles. The principle of beneficence means the provision of
      benefits for the promotion of welfare. Talking about beneficence in resuscitation
      means once again reporting stories of success, as many victims of pre- and in
      hospital sudden death have been saved in the past. Nevertheless, resuscitative
      efforts still remain unsuccessful in the majority of cases, involving the
      principle of nonmaleficence. There is potential harm in CPR. Survivors may
      recover cardiac function, but sustain severe hypoxic brain damage, at worst
      surviving without awakening for months or years. In particular, post-traumatic
      CPR is associated with an extremely poor outcome, leading to the issue of
      futility. However, futility should be defined in a strict fashion, as there might
      be an individual chance of survival. The principle of respect for autonomy means
      the right of a patient to accept or reject medical treatment, which continues in
      emergency conditions and after the patient has lost consciousness. The time frame
      in CPR requires medical decision-making within seconds, and CPR is usually
      initiated without the patient's involvement. If the patient's wish's can be
      ascertained later on, life-sustaining therapies might be withdrawn at the time.
      Terminally ill but still competent patients should be encouraged to write a no
      CPR document, which does not deny patients relief from severe symptoms, but might
      facilitate withholding resuscitative efforts at the scene. The principle of
      justice affects priorities in the allocation of health care resources. The
      decision made for a particular patient might delay or prevent emergency treatment
      in other patients who could receive greater benefit. CONCLUSIONS: The standard of
      care remains the prompt initiation of CPR. However, ethical principles such as
      beneficence, nonmaleficence, autonomy, and justice have to be applied in the
      unique setting of emergency medicine. Physicians have to consider the therapeutic
      efficacy of CPR, the potential risks, and the patient's preferences.

PMID- 9229981
TI  - [Esters and stereoisomers].
AB  - This review discusses concepts of isomers, stereoisomers, chirality, and
      enantiomers as applied to drugs used in anaesthesia. The inhalational
      anaesthetics enflurane and isoflurane are examples of stereoisomers. A chiral
      centre is formed when a carbon or quaternary nitrogen atom is connected to four
      different atoms. A molecule with one chiral centre is then present in one of two
      possible configurations termed enantiomers. A racemate is a mixture of both
      enantiomers in equal proportions. Many of the drugs used in anaesthesia are
      racemic mixtures (the inhalation anaesthetics, local anaesthetics, ketamine, and
      others). The shape of the atracurium molecule is comparable to that of a dumb
      bell:the two isoquinoline groups representing the two bulky ends connected by an
      aliphatic chain. In each isoquinoline group there are two chiral centres, one
      formed by a carbon and the other by a quaternary nitrogen atom. From a geometric
      point of view, the connections from the carbon atom to a substituted benzene ring
      and from the quaternary nitrogen to the aliphatic chain may point in the same
      direction (cis configuration) or in opposite directions (trans configuration).
      The two isoquinoline groups in atracurium are paired in three geometric
      configurations: cis-cis, trans-trans, or cis-trans. However, the two chiral
      centres allow each isoquinoline group to exist in one of four stereoisometric
      configurations. In the symmetrical atracurium molecule, the number of possible
      stereoisomers is limited to ten. Among these, 1 R-cis, 1'R-cis atracurium was
      isolated and its pharmacologic properties studied. This isomer, named cis
      atracurium, offers clinical advantages over the atracurium mixture, principally
      due to the lack of histamine-releasing propensity and the higher neuromuscular
      blocking potency. The ester groups appear in one of two steric configurations
      true and reverse esters. In the true esters, oxygen is positioned between the
      nitrogen atom and the carbonyl group, while in the reverse esters in its
      positioned on the other side of the carbonyl group. True esters, suxamethonium
      and mivacurium, are hydrolysed by the enzyme plasma cholinesterase
      (butyrylcholinesterase), albeit at different rates. The more rapid degradation of
      suxamethonium is responsible for its fast onset and short duration of action in
      comparison with mivacurium. The reverse esters, atracurium, cisatracurium, and
      remifentanil, are hydrolysed by nonspecific esterases in plasma
      (carboxyesterases). Remifentanil is hydrolysed rapidly; the degradation leads to
      its inactivation and short duration of action. Cis-atracurium is preferentially
      degraded and inactivated by a process known as Hofmann elimination. In a second
      step, one of the degradation products, the monoester acrylate, is hydrolysed by a
      nonspecific esterase.

PMID- 9229982
TI  - [Low-flow anesthesia with desflurane].
AB  - OBJECTIVES: Due to its low solubility and negligible metabolism, desflurane is
      assumed to be especially suitable for application by low-flow anaesthetic
      techniques. The aim of this clinical investigation was the development of a
      standardised dosing scheme for low-flow and minimal-flow desflurane anaesthesia.
      METHODS: One hundred six ASA status I-II patient were assigned to six groups
      according to the duration of the initial high-flow phase, fresh gas flow, and
      fresh-gas desflurane concentration. The median age, height, body weight, and
      constitution of the groups was comparable. After an initial high-flow phase using
      4.4 l/min, the fresh gas flow was reduced to 0.5 l/min (minimal-flow anaesthesia)
      or 1.0 1/min (low-flow anaesthesia). Inspired nitrous oxide concentrations were
      maintained at 60% to 70%. Using different standardised schemes of vaporizer
      settings, inspired desflurane concentrations were applied in the range from 3.4%
      to 8.7%, i.e., between 1 and 1.5 MAC. Inspired and expired desflurane
      concentrations were measured continuously by the side-stream technique and
      recorded on-line. Venous blood samples were taken immediately prior to induction
      and 45 min after flow reduction for measurement of carboxyhaemoglobin (COHb)
      concentration). RESULTS: In the 10- to 15-min initial phase during which a high
      fresh gas flow of 4.4 l/min was used, the inspired desflurane concentration
      reached values in the range of 90%-95% of the fresh gas concentration. In low
      flow anaesthesia this concentration could be maintained without any alteration of
      the vaporizer setting, whereas in minimal-flow anaesthesia with flow reduction
      the fresh gas concentration had to be increased by 1% to 2%: The quotient
      calculated by division of the inspired desflurane concentration by its fresh gas
      concentration (Q = CI/CF) ranges between 0.65 and 0.75 in animal-flow and between
      0.80 and 0.85 in low-flow anaesthesia. If use was made of the wide output range
      of the desflurane vaporizer, the inspired concentration could be increased
      rapidly by about 5% in 8 min, although the flow was kept constant at 0.5 l/min.
      Compared with its value prior to induction (2.13 +/- 1.05%), the COHb
      concentration decreased statistically significantly by about 0.7% during the 1st
      hour of minimal-flow anaesthesia (1.42 +/- 1.01%). In no case was a COHb
      concentration observed that exceeded threatening or even toxic values, although
      the soda lime was changed routinely only once a week. CONCLUSIONS: The
      pharmacokinetic properties of desflurane, resulting in especially low individual
      uptake, and the wide output range of the vaporizer facilitate the use of low-flow
      anesthetic techniques in routine clinical practice. Even in minimal-flow
      anesthesia, the duration of the initial high-flow phase can be shortened to min.
      If the flow is reduced to 1 l/min, the inspired desflurane concentration achieved
      in the initial high-flow phase can be maintained without any alteration of the
      vaporizer setting. In minimal-flow anesthesia, however, with flow reduction to
      0.5 l/min, the fresh gas concentration has to be increased to a value 1%-2%
      higher than the inspired nominal value. Due to the wide dialing range of the
      desflurane vaporizer, the amount of vapour delivered into the breathing system
      can be increased to about 110 ml/min even at a flow of 0.5 l/min. The large
      amount of agent that can be delivered into the system even under low-flow
      conditions, together with the very low individual uptake, results in a time
      constant that is sufficient short for the clinically required rapid increase in
      inspired desflurane concentrations. The short time-constant of low-flow
      desflurane anaesthesia improves the control of the anaesthetic concentration. If
      all measures are taken to safely avoid inadvertent drying out of the soda lime,
      there is no evidence that low-flow anaesthesia with desflurane is liable to
      increase the risk of accidental carbon monoxide poisoning. (ABSTRACT TRUNCATED)

PMID- 9229983
TI  - [The effects of aprotinin. Blood loss and coagulation parameters in orthotopic
      liver transplantation: A clinical-experimental, prospective and randomized double
      blind study].
AB  - The effect of aprotinin (2,000,000 IU as a bolus +500,000 JU/h until the end of
      the operation) on transfusion requirements and coagulation parameters in
      orthotopic liver transplantation (study group: n = 9; placebo group: n = 9) was
      investigated in a randomised, double-blind study. Coagulation parameters were
      monitored intraoperatively using a mobile laboratory. In contrast to the
      published results, no effect on transfusion requirements could be demonstrated.
      However, aprotinin showed a positive effect on some coagulation parameters in the
      reperfusion phase. The mechanism appeared to be inhibition of the contact
      activation of the intrinsic system with less thrombin generation in the study
      group.

PMID- 9229984
TI  - [The necessity for perioperative cortisol substitution. Spontaneous and
      stimulated ACTH and cortisol secretion during unilateral adrenalectomy for renal
      cell carcinoma].
AB  - Impaired adrenal function during perioperative stress carries the risk of acute
      cortisol (Cs) deficiency (Addisonian crisis), which may be critical without Cs
      supplementation. Thus, with evidence of dysfunction of the adrenal glands
      perioperative substitution is indicated. However, it is unclear whether
      unilateral adrenalectomy may attenuate the adrenocorticoid response.
      Glucocorticosteroids are potent agents with several well-known side effects. The
      purpose of the present study was to evaluate if routine Cs supplementation is
      justified and necessary in patients undergoing adrenalectomy during nephrectomy
      for renal-cell cancer. METHODS: Ten consecutive patients with renal-cell cancer
      (5 male, 5 female; age 58 +/- 10 years; ASA class I-II) who underwent
      adrenalectomy with radical nephrectomy were included in this study. None of them
      had received steroids for at least 5 years prior to the current surgery.
      Anaesthesia was induced with propofol, fentanyl, and vecuronium and maintained
      with isoflurane (PetIso: 0.8 +/- 0.3 vol.%) in nitrous oxide (66%) and oxygen.
      The patients did not receive any Cs treatment perioperatively. Monitoring
      included heart rate (beats/min), mean arterial pressure (mm Hg), central venous
      pressure (mm Hg), O2 saturation (%), and body temperature (degrees C, rectal).
      Plasma analyses included Cs (Cs radioimmunoassay IBL; normal 120-250 ng/ml),
      adrenocorticotropic hormone (ACTH) (ACTH-II IRMA; normal (10-50 pg/ml), glucose,
      and electrolytes determined as follows: preoperatively (8 a.m.); 1-6 h (60-min
      intervals) after surgery; pre-corticotropin-releasing hormone (CRH) (Corticobiss:
      2 micrograms/kg i.v.) administration (1st postop. day at 8 a.m. and after 30, 60,
      90, and 120 min. The study was completed with plasma analyses on postoperative
      days 2 and 3 (8 a.m.). RESULTS: None of the patients showed any clinical signs of
      plasma parameter of adrenal insufficiency due to the unilateral adrenalectomy.
      Serum levels (median: 25%/75% percentiles) of Cs (maximum [max.]:253 [217/288]
      ng/ml) and ACTH (max.:347 ([68/405] pg/ml) were elevated above the normal range
      postoperatively). After intravenous stimulation with CRH (1st postoperative day),
      Cs (max.:273 [248/310] ng/ml) and ACTH (max.: 107 ([75/275] pg/ml) were also
      increased above normal. During postoperative days 2 and 3 (8 a.m.) Cs and ACTH
      remained in the high-normal range. CONCLUSIONS: Data from this study indicate
      that unilateral adrenalectomy was associated with adequate spontaneous Cs
      secretion by the remaining adrenal gland. Moreover, stimulation with CRH
      demonstrated adequate reactivity of the pituitary-adrenal axis. None of the
      patients showed any signs of Cs deficiency by clinical or serum parameters.
      Therefore, we do not recommend routine Cs supplementation in patients undergoing
      adrenalectomy during tumor nephrectomy, nevertheless, Cs supplementation remains
      necessary for patients with primary hypothalamic-pituitary-adrenal dysfunction
      (Addison's disease) or hyperfunction (Cushing's disease).

PMID- 9229986
TI  - [Continuous measurement of jugular venous blood gas. A case of subarachnoid
      bleeding].
AB  - INTRODUCTION: Recently, a compact multisensor device 0.5 mm in diameter has
      become available with a miniaturised Clark electrode for measuring blood oxygen
      tension and two optical fibres for measuring CO2 tension, pH, and temperature
      (Paratrend 7, Biomedical Sensors, High Wycombe, UK). We used this new probe for
      continuous blood gas monitoring in the jugular bulb as an alternative to the
      commonly used fiberoptic spectrophotometric oximetric measurement of haemoglobin
      saturation. RESULTS: A 64-year-old patient was admitted for surgery of a right
      sided intracranial aneurysm. During surgery, with no artefacts or evidence of
      catheter drift, a normal jugular venous pO2 (pjvO2) of 39 +/- 3 mmHg was
      measured. Over the period of weaning, two declines in pjvO2 occurred (22.5 and
      18.7 mm Hg) associated with a decline in CO2 tension and a rise in pH. We treated
      these events successfully by analgosedation, controlled ventilation with an
      inspired oxygen fraction of 70%, and elevation of the mean arterial blood
      pressure to over 100 mmHg. Extubation was possible about 24 h later. Furthermore,
      3 h after extubation pjvO2 values could be monitored without difficulty despite
      movement of the patient. DISCUSSION: The technique of polarographically measuring
      pjvO2 with a Clark-type probe appears superior to fibreoptic jugular venous
      oximetry due to the clearly lower incidence of faulty measurements, especially in
      the intensive care unit, where patients undergo frequent nursing interventions
      and tend to awaken. We did not even observe artefacts due to patient movement
      after extubation. A limitation of the new multisensor system might be the
      distance of 4 cm between the sensor tip and the end of the insertion catheter,
      which makes samples drawn for in vitro blood gas analyses to control the
      continuous monitoring less comparable. Improvements in the construction of the
      probe are recommended.

PMID- 9229985
TI  - [Small-volume resuscitation for hypovolemic shock. Concept, experimental and
      clinical results].
AB  - The concept of small-volume resuscitation, the rapid infusion of a small volume
      (4 ml/kg BW) of hyperosmolar 7.2-7.5% saline solution for the initial therapy of
      severe hypovolemia and shock was advocated more than a decade ago. Numerous
      publications have established that hyperosmolar saline solution can restore
      arterial blood pressure, cardiac index and oxygen delivery as well as organ
      perfusion to pre-shock values. Most prehospital studies failed to yield
      conclusive results with respect to a reduction in overall mortality. A meta
      analysis of preclinical studies from North and South America, however, has
      indicated an increase in survival rate by 5.1% following small-volume
      resuscitation when compared to standard of care. Moreover, small-volume
      resuscitation appears to be of specific impact in patients suffering from head
      injuries with increased ICP and in severest trauma requiring immediate surgical
      intervention. Results from clinical trials in Austria, Germany and France have
      demonstrated positive effects of hyperosmolar saline solutions when used for
      fluid loading or fluid substitution in cardiac bypass and in aortic aneurysm
      surgery, respectively. A less positive perioperative fluid balance, a better
      hemodynamic stability and improved pulmonary function were reported. In septic
      patients oxygen consumption could significantly be augmented. The most important
      mechanism of action of small-volume resuscitation is the mobilisation of
      endogenous fluid primarily from oedematous endothelial cells, by which the
      rectification of shock-narrowed capillaries and the restoration of nutritional
      blood, flow is efficiently promoted. Moreover, after ischemia reperfusion a
      reduction in sticking and rolling leukocytes have been found following
      hyperosmolar saline infusion. Both may be of paramount importance in the long
      term preservation of organ function following hypovolemic shock. An increased
      myocardial contractility in addition to the fluid loading effects of hyperosmolar
      saline solutions has been suggested as a mechanism of action. This, however,
      could not be confirmed by pre-load independent measures of myocardial
      contractility. Some concerns have been raised regarding the use of hyperosmolar
      saline solutions in patients with a reduced cardiac reserve. A slower speed of
      infusion and adequate monitoring is recommended for high risk patients. Recently,
      hyperosmolar saline solutions in combination with artificial oxygen carriers have
      been proposed to increase tissue oxygen delivery through enhanced O2 content.
      This interesting perspective, however, requires further studies to confirm the
      potential indications for such solutions. Many hyperosmolar saline colloid
      solutions have been investigated in the past years, from which 7.2-7.5% sodium
      chloride in combination with either 6-10% dextran 60/70 or 6-10% hydroxyethyl
      starch 200,000 appear to yield the best benefit-risk ratio. This has led to the
      registration of the solutions in South America, Austria, The Czech Republic, and
      is soon awaited for North America.

PMID- 9229987
TI  - [Remifentanil with propofol or isoflurane. A comparison of the recovery times
      after arthroscopic surgery].
AB  - OBJECTIVES: Due to its unique pharmacokinetics, the new esterase-metabolised
      opioid remifentanil results in rapid post-anesthesia recovery. The aim of this
      clinical investigation was to compare recovery times after remifentanil
      anaesthesia in combination with hypnotic concentrations of either propofol or
      isoflurane. Dosages used in the study protocol were based on recommendations by
      the pharmaceutical manufacturer. METHODS: Patients (ASA status I-II) scheduled
      for elective arthroscopy were included in this trial. Without premedication in
      the morning, anaesthesia was induced identically in both groups: remifentanil
      bolus (1 microgram/kg), start of remifentanil-infusion (0.5 micrograms/kg/min),
      followed immediately by propofol (ca. 2 mg/kg). For maintenance of anaesthesia
      remifentanil (0.25 micrograms/kg/min) was combined with either a propofol
      infusion of 0.1 mg/kg/min or 0.5 MAC isoflurane (= 0.6 vol. %) in O2/air.
      Anaesthetic delivery was discontinued simultaneously with termination of surgery
      and recovery times were recorded. RESULTS: A total of 40 patients were studied at
      random in two groups of 20 each with comparable demographic data and anaesthetic
      technique (Tables 1 and 2). In both groups emergence was very rapid. Recovery
      times were significantly shorter for remifentanil-isoflurane than for
      remifentanil-propofol (Table 3): spontaneous ventilation 5.1 vs 8.1 min (P <
      0.05), extubation 5.5 vs 8.6 min (P < 0.02), post-anaesthesia recovery score > or
      = 9 of 10 points 6.2 vs 11.3 min (P < 0.01), and arrival at PACU 16.2 vs 19.2 min
      (P < 0.01). Mild to moderate shivering was noted in 40% of all patients (9 cases
      following isoflurane, 7 following propofol). CONCLUSIONS: Using the
      manufacturer's recommended dosages, emergence after remifentanil anaesthesia is
      more rapid with 0.5 MAC isoflurane than with 0.1 mg/kg/min propofol. These
      results are most probably due to the different pharmacological properties of both
      co-anaesthetics, especially the applied dosages, and to different interactions
      with remifentanil. Present clinical experience suggests that a further dose
      reduction, especially for propofol, is possible. For both remifentanil groups
      emergence was remarkably rapid between return of consciousness and the awake
      state (on-off phenomenon), which might contribute to post-anaesthesia safety.

PMID- 9229988
TI  - [Organ specific expression pattern of a carbon monoxide generating stress protein
      (hemoxygenase-1/heatshock protein 32) following hemorrhagic shock].
AB  - OBJECTIVE: Recent evidence suggests a possible role for Haeme oxygenase (HO)
      derived carbon monoxide (CO) in the regulation of vascular tone through elevation
      of cyclic 3'-5' guanosine monophosphate (cGMP). Previous work from our laboratory
      has shown that blockade of the HO pathway by tin-protoporphyrin-IX (SnPP) after
      resuscitation from hemorrhage leads to a specific and profound increase in portal
      resistance while neither systemic nor hepatic arterial resistance are affected.
      We therefore investigated the organ-specific expression pattern of the stress
      inducible protein haeme oxygenase-1/heat shock protein 32 after haemorrhage and
      resuscitation. MATERIALS AND METHODS: After approval of the protocol by the local
      review board, male Sprague-Dawley rats (n = 6/group) were anaesthetised with
      pentobarbitone, instrumented for assessment of central haemodynamics and
      subjected to haemorrhagic hypotension (40 mm Hg for 1 h) followed by
      resuscitation with 60% shed blood and Ringer's solution or a time-matched sham
      protocol. Samples of liver, spleen, kidney intestine, aorta, and lungs were
      harvested 5 h after the onset of resuscitation and subjected to Western-blot
      analysis using a specific anti-rat HO-1/hsp 32 antibody (StressGen, Sidney,
      Canada). RESULTS: Resuscitation with shed blood/Ringer's solution restored
      central haemodynamics and acid-base status while significant haemodilution was
      observed. Haemorrhage and resuscitation led to strong induction of HO-1 in the
      liver and slight induction in aortic tissue, while no increase in steady-state
      protein levels was observed in the other organs studied. CONCLUSION: These
      results suggest a specific contribution of the HO/CO pathway to maintenance of
      low hepatic portal resistance in vivo in a clinically relevant model of
      haemorrhagic shock and adequate resuscitation.

PMID- 9229989
TI  - [Ethical-judicial aspects of postoperative patient support].

PMID- 9229990
TI  - [New muscle relaxants. Update on mivacurium, rocuronium and cis-atracurium].

PMID- 9229991
TI  - [Therapy reduction in intensive care "allowing the patient to die" by concious
      withdrawal of medical procedures. Remarks on the work of T. Prien and P. Lawin.
      Anaesthesist (1996) 45:176-182].

PMID- 9229992
TI  - [The laryngeal mask--a valuable instrument for difficult intubation in children.
      Remarks on the work of R. Ofer and H. Dworzak. Anaesthesist (1996) 45:268-270].

PMID- 9229993
TI  - [The difficult intubation in adults. Remarks on the work of H. Langenstein and G.
      Cunitz Anaesthesist (1996) 45:372-383].

PMID- 9229994
TI  - [Post-traumatic splenectomy].

PMID- 9229995
TI  - [Observations of the development of the equine distal interphalangeal joint
      cavity concerning the pelvic limb of fetuses, fillies and adult horses].
AB  - Ten horses, younger than 1 year, were used to investigate the articulatio
      interphalangea distalis of the pelvic limb. The expansion of the dorsal recess
      was compared to those of adult horses. The recessus dorsalis always formed a
      shape like the letter 'm' or like a triangle with oblique angles. Consequently
      the great proximo-distal expansion on the medial side of the dorsal recess very
      probably has nothing to do with the age of horses.

PMID- 9229996
TI  - Twenty-five years of Annals of Emergency Medicine: a history.

PMID- 9229997
TI  - Cultural malpractice. The growing obsolescence of psychology with the changing
      U.S. population.
AB  - With the changing demographics occurring in the United States, psychology must
      make substantive revisions in its curriculum, training, research, and practice.
      Without these revisions, psychology will risk professional, ethical, and economic
      problems because psychology will no longer be a viable professional resource to
      the majority of the U.S. population. In particular, this article discusses the
      need for psychology to address issues of ethnicity/culture, gender, and sexual
      orientation.

PMID- 9229998
TI  - Clinical features of genetic hemochromatosis in women compared with men.
AB  - BACKGROUND: The clinical expression of hemochromatosis is presumed to be less
      frequent and less severe in women than in men because of the iron loss associated
      with menses and pregnancy, but this hypothesis has not been validated. OBJECTIVE:
      To compare the clinical features of women who have genetic hemochromatosis with
      those of men who have the disease. DESIGN: Cross-sectional study. SETTING:
      Tertiary referral centers for hemochromatosis in France and Canada. PATIENTS: 176
      women and 176 men with hemochromatosis, matched for year of birth. MEASUREMENTS:
      Age at presentation, clinical symptoms, transferrin saturation, serum ferritin
      level, hepatic iron concentration, and hepatic iron index. RESULTS: Hepatic iron
      concentration and hepatic iron index were similar in men and women. Women had
      lower serum ferritin levels than men did (911 micrograms/L compared with 1911
      micrograms/L; mean difference, 1000 micrograms/L [95% CI, 669 micrograms/L to
      1331 micrograms/L]) and less iron removed by venesections (5.5 g and 8.6 g; mean
      difference, 3.1 g [CI, 1.5 g to 4.8 g]). Compared with women, men had a higher
      incidence of cirrhosis (25.6% and 13.8%; mean difference, 11.8 percentage points
      [CI, 3.2 to 20.4 percentage points]) and diabetes (15.9% and 7.4%; mean
      difference, 8.5 percentage points [CI, 1.9 to 5.2 percentage points]). Compared
      with men, women had a higher incidence of fatigue (64.8% and 42%; mean
      difference, -22.8 percentage points [CI, -32.9 to -12.5 percentage points]) and
      pigmentation (48% and 44.9%; mean difference, -13.1 percentage points [CI, -23.4
      to 2.7 percentage points]). Hepatic iron concentration and hepatic iron index
      were greater in women in whom menstruation had stopped before 50 years of age.
      Serum ferritin levels and transferrin saturation were normal in 6.2% of women and
      0% of men. CONCLUSIONS: Women with genetic hemochromatosis can have full
      phenotypic expression of the disease, including cirrhosis. Recognizing the
      nonspecific nature of presenting symptoms in women is essential for early
      diagnosis and treatment.

PMID- 9229999
TI  - Coronary heart disease incidence and survival in African-American women and men.
      The NHANES I Epidemiologic Follow-up Study.
AB  - BACKGROUND: Relatively few data are available on risk for or survival with
      coronary heart disease in African-American persons. OBJECTIVE: To determine
      whether incidence of coronary heart disease, rate of survival with the disease,
      and rate of coronary surgery differ between ethnic groups. DESIGN: Prospective
      cohort study. SETTING: United States. PARTICIPANTS: Persons who responded to the
      National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow
      up Study. Included in this analysis were 11406 white persons and African-American
      persons aged 25 to 74 years who had no history of coronary heart disease. Average
      follow-up for survivors was 19 years (maximum, 22 years). MEASUREMENTS: Incident
      coronary heart disease. RESULTS: Compared with that in white persons, the age
      adjusted risk for coronary heart disease was higher in African-American women
      aged 25 to 54 years (relative risk, 1.76 [95% CI, 1.36 to 2.29]) but was lower in
      African-American men within each age subgroup. The age-adjusted risk was lower in
      African-American men for all ages combined (25 to 74 years) (relative risk, 0.78
      [CI, 0.65 to 0.93] for coronary heart disease and 0.62 [CI, 0.42 to 0.92] for
      acute myocardial infarction). The higher rate in African-American women aged 25
      to 54 years could be explained statistically by the higher risk factor levels in
      these women. Ethnic groups did not significantly differ in survival after the
      first hospitalization for coronary heart disease. However, the incidence of
      coronary procedures after hospitalization for coronary heart disease was markedly
      lower in African-American persons than in white persons (age- and sex-adjusted
      relative risk, 0.40 [CI, 0.16 to 0.99]). CONCLUSIONS: Total incidence of coronary
      heart disease is higher in African-American women aged 25 to 54 years than in
      white women of the same ages and is lower in African-American men aged 25 to 74
      years than in white men of the same ages.

PMID- 9230000
TI  - Crystalluria and urinary tract abnormalities associated with indinavir.
AB  - BACKGROUND: Indinavir, a protease inhibitor widely used to treat patients with
      HIV infection, has been associated with nephrolithiasis. Distinctive urinary
      crystals and a spectrum of urologic disorders were noted in patients receiving
      indinavir. OBJECTIVE: To determine the composition of urinary crystals and the
      frequency of asymptomatic crystalluria and urinary tract symptoms in patients
      receiving indinavir. PATIENTS: Patients with HIV infection who were enrolled in
      studies conducted at the National Institutes of Health. MEASUREMENTS: Microscopic
      urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry
      of urinary crystals and stones, and clinical evaluation of patients with urologic
      symptoms. RESULTS: Of 240 patients receiving indinavir, 142 provided urine
      specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like
      rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC
      confirmed that these crystals were composed of indinavir. Of 40 patients who were
      not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the
      240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7
      (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed
      syndromes: crystalluria associated with dysuria and crystalluria associated with
      back or flank pain. Four of the patients with the latter syndrome had
      radiographic evidence of intrarenal sludging. CONCLUSIONS: Indinavir forms
      characteristic crystals in the urine. This crystalluria may be associated with
      dysuria and urinary frequency, with flank or back pain associated with intrarenal
      sludging, and with the classic syndrome of renal colic.

PMID- 9230001
TI  - Emergency department use of aspirin in patients with possible acute myocardial
      infarction.
AB  - BACKGROUND: Efforts have been made to improve the suboptimal use of aspirin after
      hospitalization. OBJECTIVE: To assess the frequency and timing of aspirin
      administration in emergency department patients with possible myocardial
      infarction. DESIGN: Retrospective record review. SETTING: Emergency departments
      of four hospitals affiliated with the same university. PATIENTS: All patients who
      were admitted to the four hospitals in 1994 for evaluation and treatment of
      suspected acute myocardial infarction. MEASUREMENTS: The frequency and timing of
      aspirin administration and the definitive diagnosis established before discharge
      from the hospital. RESULTS: Aspirin was not given to 253 of 463 emergency
      department patients (55%) who had a definitive diagnosis of acute myocardial
      infarction. Seventy-eight percent of patients who did receive aspirin received it
      more than 30 minutes after arrival in the emergency department. CONCLUSION:
      Aspirin therapy is underutilized as the first intervention in patients who are
      admitted with suspected myocardial infarction.

PMID- 9230002
TI  - Culture-confirmed infection and reinfection with Borrelia burgdorferi.

PMID- 9230003
TI  - Short-course, low-dose amphotericin B lipid complex therapy for visceral
      leishmaniasis unresponsive to antimony.
AB  - BACKGROUND: Visceral leishmaniasis (kala-azar) is a worldwide, disseminated
      intracellular protozoal infection for which prolonged, conventional therapy with
      pentavalent antimony has become increasingly less effective. OBJECTIVE: To
      determine the efficacy and minimal effective dose of short-course therapy with
      amphotericin B lipid complex in visceral leishmaniasis. DESIGN: A randomized,
      open-label study. SETTING: Inpatient kala-azar treatment unit in the state of
      Bihar in northeast India, where visceral leishmaniasis is endemic. PATIENTS: 60
      patients with active infection who had not responded to or who had relapse after
      receiving conventional (> 30 days) treatment with pentavalent antimony.
      INTERVENTION: Intravenous amphotericin B lipid complex was given once daily for 5
      consecutive days by 2-hour infusion. Patients were randomly assigned to receive
      1, 2, or 3 mg/kg of body weight per day (total doses of 5, 10, or 15 mg/kg,
      respectively). MEASUREMENTS: Clinical and parasitologic responses (the latter
      were measured by parasite density score of the splenic aspirate) were determined
      14 days after treatment. Definitive responses were assessed 6 months after
      treatment according to clinical outcomes and findings on examination of bone
      marrow aspirate. RESULTS: All 60 patients responded to 5 days of treatment.
      Fourteen days after therapy, all patients had parasite-free splenic aspirates and
      were considered to have an apparent clinical and parasitologic response. Six
      months after therapy, definitive responses were documented in 16 of 19 (84% [95%
      Cl, 60% to 97%]), 18 of 20 (90% [Cl, 68% to 99%]), and 21 of 21 (100% [Cl, 84% to
      100%]) patients who received total doses of 5, 10, and 15 mg/kg, respectively.
      CONCLUSION: Short-course therapy with low-dose amphotericin B lipid complex is
      effective for visceral leishmaniasis and is an important therapeutic alternative
      in the management of this serious intracellular protozoal infection.

PMID- 9230004
TI  - Maintaining the confidentiality of medical records shared over the Internet and
      the World Wide Web.
AB  - The Boston Electronic Medical Record Collaborative is working to develop a system
      that will use the World Wide Web to transfer computer-based patient information
      to clinicians in emergency departments. Maintaining adequate confidentiality of
      these records while still facilitating patient care is paramount to this effort.
      This paper describes an explicit protocol that would make it possible to
      electronically identify patients and providers, secure permission for release of
      records, and track information that is transmitted. It is hoped that other,
      similar efforts now underway will be able to use and build on this model. Comment
      on this proposal is invited from all parties with an interest in confidentiality.
      The system will be used only with "scrubbed" data-data from which all identifiers
      have been removed-until it is generally agreed that the confidentiality methods
      proposed here are appropriate and sufficient.

PMID- 9230005
TI  - Observations on asthma mortality.
AB  - The rate of death from asthma in the United States has been increasing over the
      last decade, but such deaths still remain uncommon. Mortality rates differ
      markedly by region and ethnicity, and case-fatality rates are highest in black
      men living in inner cities. In general, patients in greatest jeopardy are those
      with severe, unstable disease who are not being objectively monitored; however,
      death can occur in anyone if the attack is intense enough. Sudden catastrophic
      episodes of asthma occur but are very rare. Failure to recognize the seriousness
      of the terminal episode or to treat the episode appropriately remains the chief
      contributing cause of poor outcome. Little compelling evidence shows that adverse
      effects of medications play much of a role in asthma-related death. The disease
      characteristics that place patients at risk remain inadequately defined. Of those
      suggested, only a history of recurrent hospitalization and the need for
      ventilatory assistance are specific enough to be helpful. These characteristics,
      however, are found in only 36% and 6% of cases, respectively; thus, their absence
      is of no value in assessing risk. The prognosis after a near-fatal episode of
      asthma is poor, and approximately 10% of patients die in the year after the
      event. Given the current state of knowledge, it is wise to view all exacerbations
      of asthma that last longer than a few days as potentially fatal and to treat them
      accordingly. This is especially true in patients who have previously had a severe
      episode of asthma.

PMID- 9230006
TI  - Mr. Gates's summer vacation: a centennial remembrance.
AB  - In 1897, Frederick T. Gates, a Baptist minister and adviser to John D.
      Rockefeller Sr., read the entire second edition of The Principles and Practice of
      Medicine by William Osler while on a summer vacation at Lake Liberty, New York.
      The book reinforced the low opinion Gates had of the efficacy of medicine but
      convinced him that medical science would be a wise investment for the Rockefeller
      fortune. The results of this investment included the Rockefeller Institute for
      Medical Research, the General Education Board, the Rockefeller Foundation, and
      the International Health Board. Gates sponsored Rockefeller funding of full-time
      clinical professorships, an idea that Osler opposed but that eventually became
      the prevailing model for medical departments at universities in the United
      States.

PMID- 9230007
TI  - Putting some muscle into osteoarthritis.

PMID- 9230008
TI  - Global eradication of poliomyelitis and measles: another quiet revolution.

PMID- 9230009
TI  - On retirement.

PMID- 9230010
TI  - Hyponatremia and myelinolysis.

PMID- 9230011
TI  - Pregnancy-related thromboembolism.

PMID- 9230012
TI  - Pregnancy-related thromboembolism.

PMID- 9230013
TI  - Pregnancy-related thromboembolism.

PMID- 9230014
TI  - Update in infectious diseases.

PMID- 9230015
TI  - The illusion of deterministic rules.

PMID- 9230016
TI  - The illusion of deterministic rules.

PMID- 9230017
TI  - Hantavirus antibodies in New York.

PMID- 9230018
TI  - Paraneoplastic autoimmune xerostomia.

PMID- 9230019
TI  - Intracranial hypertension and minocycline.

PMID- 9230020
TI  - Thyrotoxicosis factitia veterinarius.

PMID- 9230021
TI  - Mycobacteriosis in the Pliocene.

PMID- 9230022
TI  - Protracted cholestatic hepatitis after the use of prostata.

PMID- 9230023
TI  - Fatal phenformin-associated lactic acidosis.

PMID- 9230024
TI  - A return to Farr and Nightingale.

PMID- 9230025
TI  - Twain: differences of opinion on the worthiest of all occupations.

PMID- 9230026
TI  - On bedside teaching.

PMID- 9230027
TI  - On bedside teaching.

PMID- 9230028
TI  - On bedside teaching.

PMID- 9230029
TI  - On bedside teaching.

PMID- 9230030
TI  - On bedside teaching.

PMID- 9230031
TI  - On bedside teaching.

PMID- 9230032
TI  - On bedside teaching.

PMID- 9230033
TI  - Doing the little things.

PMID- 9230034
TI  - Physician-assisted suicide.

PMID- 9230035
TI  - Quadriceps weakness and osteoarthritis of the knee.
AB  - BACKGROUND: The quadriceps weakness commonly associated with osteoarthritis of
      the knee is widely believed to result from disuse atrophy secondary to pain in
      the involved joint. However, quadriceps weakness may be an etiologic factor in
      the development of osteoarthritis. OBJECTIVE: To explore the relation between
      lower-extremity weakness and osteoarthritis of the knee. DESIGN: Cross-sectional
      prevalence study. SETTING: Population-based, with recruitment by random-digit
      dialing. PARTICIPANTS: 462 volunteers 65 years of age or older. MEASUREMENTS:
      Radiographs of the knee were graded for the presence of osteoarthritis. Knee pain
      and function were assessed with the Western Ontario and McMaster Universities
      Arthritis Index, the strength of leg flexors and extensors was assessed with
      isokinetic dynamometry, and lower-extremity lean tissue mass was assessed with
      dual-energy x-ray absorptiometry. RESULTS: Among participants with
      osteoarthritis, quadriceps weakness, but not hamstring weakness, was common. The
      ratio of extensor strength to body weight was approximately 20% lower in those
      with than in those without radiographic osteoarthritis. Notably, among women with
      tibiofemoral osteoarthritis, extensor weakness was present in the absence of knee
      pain and was seen in participants with normal lower-extremity lean mass (extensor
      strength, 30.1 lb-ft for those with osteoarthritis and 34.8 lb-ft for those
      without osteoarthritis; P < 0.001). After adjustment for body weight, age, and
      sex, lesser quadriceps strength remained predictive of both radiographic and
      symptomatic osteoarthritis of the knee (odds ratio for prevalence of
      osteoarthritis per 10 lb-ft loss of strength, 0.8 [95% CI, 0.71 to 0.90] for
      radiographic osteoarthritis and 0.71 [CI, 0.51 to 0.87] for symptomatic
      osteoarthritis). CONCLUSION: Quadriceps weakness may be present in patients who
      have osteoarthritis but do not have knee pain or muscle atrophy; this suggests
      that the weakness may be due to muscle dysfunction. The data are consistent with
      the possibility that quadriceps weakness is a primary risk factor for knee pain,
      disability, and progression of joint damage in persons with osteoarthritis of the
      knee.

PMID- 9230036
TI  - B Lymphocytes and Autoimmunity. Proceedings of a conference. Prague, Czech
      Republic, May 21-25, 1996.

PMID- 9230038
TI  - Ross-Konno operation with resection of endocardial fibroelastosis for critical
      aortic stenosis with borderline-sized left ventricle in neonates.

PMID- 9230037
TI  - Blue nodules in a newborn. Neuroblastoma.

PMID- 9230039
TI  - Defining cooking salt intakes for patient counselling and policy making.
AB  - The role of salt (NaCl) in the development of high blood pressure has been a
      matter of debate, however, the Intersalt Study showed that sodium (Na) intake in
      various areas of the World is related to the slope of blood pressure with age.
      Accurate amounts of the total salt intake or that coming from a particular source
      are needed, both, for physicians who need to consider the salt intake of their
      patients and for public health workers who are in charge of the implementation of
      public health programs where salt is used as a carrier of other nutrients. An
      analysis of the literature suggests that exaggerated values for total salt
      intakes have often been obtained from indirect estimates; discretionary salt use,
      i.e. home-cooking salt has invariably been overestimated. A method is described
      for measuring the contribution of cooking salt to total salt intake since it is a
      confusing area where inappropriate methods have been used to assess its
      contribution. The method described is based on the use of small amounts of
      lithium carbonate fused with NaCl. Validation experiments were undertaken to
      determine the naturally occurring lithium (Li) in a number of foods including
      fresh, frozen and tinned vegetables, and the use of Li tagged salt for cooking
      vegetables and for direct use in cooked foods. We also assessed whether Li was
      taken up proportionally with Na into foods during cooking. In general vegetables
      contained variable but only small amounts of Li except aubergine and spinach, and
      Li was taken up proportionally with Na in a variety of vegetables. Results showed
      that 36, 35 and 21% of the salt added during cooking was recovered in carrots,
      runner beans and potatoes respectively, the rest being discarded in the cooking
      water. This suggest that about a third of salt added during the cooking of
      vegetables will be ingested by the household. Attempts to rely simply on the
      total use of household salt supplies will clearly exaggerate, markedly, the true
      intake of individuals.

PMID- 9230040
TI  - A unique cellular myosin II exhibiting differential expression in the cerebral
      cortex.

PMID- 9230041
TI  - EPR study of the mixed-valent diiron sites in mouse and herpes simplex virus
      ribonucleotide reductases. Effect of the tyrosyl radical on structure and
      reactivity of the diferric center.
AB  - Reduction of ribonucleotide reductase (EC 1.17.4.1) R2 proteins in a frozen
      glycerol-buffer solution at 77 K by mobile electrons generated by gamma
      irradiation produces EPR-detectable iron sites in mixed-valent Fe(II)/Fe(III)
      states. The primary EPR signals give information about the ligand arrangement of
      the diferric form of the iron site, whereas secondary signals observed after
      annealing of the sample show the effects of structural relaxation. In recombinant
      metR2 proteins (without free radical) from mouse and herpes virus type 1, the
      mixed-valent sites trapped at 77 K give rise to axial S = 1/2 EPR spectra with g
      values in the range 1.79-1.94, observable at temperatures up to 110 K. The
      spectra are assigned to mu-oxo-bridged dinuclear iron sites. In mouse metR2, the
      primary EPR spectrum is a mixture of two components. Annealing the R2 samples to
      160-170 K transforms the primary EPR signals into rhombic spectra, characterized
      by gav < 1.8, and observable only below 25 K. These spectra are assigned to
      partially relaxed forms with a mu-hydroxo bridge, formed by protonation of the
      oxo bridge. Further annealing at 220 K produces new rhombic EPR spectra, which
      are closely similar with those observed and found to be stable after chemical
      reduction at room temperature. The EPR signal of the primary mixed-valent iron
      site in active mouse R2 protein with a tyrosyl radical also has two components.
      Both are different from those observed in metR2. In herpes simplex virus type 1
      protein R2, one primary mixed-valent component was observed for the met protein.
      The dose-yield curve for the mixed-valent state in active mouse R2 is sigmoidal
      in shape, indicating that the tyrosyl radical is reduced by mobile electrons
      before the iron site. Kinetic experiments on the reduction by dithionite on mouse
      R2 without and with radical show a significantly enhanced rate for reduction of
      the iron site in the protein without radical. The results suggest that in active
      mouse R2 only complete diferric sites with neighboring radicals give rise to the
      mixed-valent spectra, and that these sites may exist in two structurally distinct
      forms. The results on the mouse R2 proteins confirm and extend previous results
      obtained on the Escherichia coli protein R2 showing that the presence of the
      tyrosyl radical significantly affects not only the structure but also the
      reactivity of the iron site.

PMID- 9230042
TI  - A naturally occurring protective system in urea-rich cells: mechanism of osmolyte
      protection of proteins against urea denaturation.
AB  - Trimethylamine N-oxide (TMAO) is a solute concentrated in the urea-rich cells of
      elasmobranchs and coelacanth to offset the damaging effects of urea on
      intracellular protein structure and function. On the basis of transfer free
      energy measurements, favorable interaction of TMAO with amino acid side chains
      promote protein denaturation. This effect is more than offset by highly
      unfavorable TMAO-peptide backbone interactions that not only oppose denaturation
      but also provide stabilization against denaturation by urea. By combining
      transfer free energies of side chains and backbone with surface area exposure in
      the native and unfolded states of ribonuclease T1, the transfer free energies of
      native and unfolded protein from water to 1 M TMAO are estimated as 1.7 and 5.9
      kcal/mol, respectively. These estimates agree favorably with the respective
      values of 1.2 and 5.4 kcal/mol determined experimentally by Lin and Timasheff
      [(1994) Biochemistry 33, 12695-12701]. The unfavorable transfer free energies of
      native and unfolded protein from water to TMAO provides a molecular level
      rationale for preferential hydration of proteins by osmolytes. Promotion of
      denaturation by urea is found to be offset by TMAO in a manner that is roughly
      additive of the combined effects of both solutes. The favorable interaction of
      urea with the backbone provides the dominant driving force for protein unfolding
      by this denaturant, and the unfavorable interaction of TMAO with backbone is the
      dominant force opposing urea denaturation. In solutions that contain significant
      organic solute concentration, the ascendance of the role of the peptide backbone
      over that of side chains can explain many observed effects in protein
      denaturation and stability induced by a variety of stabilizing and destabilizing
      organic solutes.

PMID- 9230043
TI  - Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein.
AB  - The backbone 1H, 13C, and 15N resonances of the c-Ha-Ras protein [a truncated
      version consisting of residues 1-171, Ras(1-171)] bound with GMPPNP (a slowly
      hydrolyzable analogue of GTP) were assigned and compared with those of the GDP
      bound Ras(1-171). The backbone amide resonances of amino acid residues 10-13, 21,
      31-39, 57-64, and 71 of Ras(1-171).GMPPNP, but not those of Ras(1-171).GDP, were
      extremely broadened, whereas other residues of Ras(1-171).GMPPNP exhibited amide
      resonances nearly as sharp as those of Ras(1-171). GDP. The residues exhibiting
      the extreme broadening, except for residues 21 and 71, are localized in three
      functional loop regions [loops L1, L2 (switch I), and L4 (switch II)], which are
      involved in hydrolysis of GTP and interactions with other proteins. From the
      temperature and magnetic field strength dependencies of the backbone amide
      resonance intensities, the extreme broadening was ascribed to the exchange at an
      intermediate rate on the NMR time scale. It was shown that the Ras(1-171) protein
      bound with GTP or GTPgammaS (another slowly hydrolyzable analogue of GTP)
      exhibits the same type of broadening. Therefore, it is a characteristic feature
      of the GTP-bound form of Ras that the L1, L2, and L4 loop regions, but not other
      regions, are in a rather slow interconversion between two or more stable
      conformers. This phenomenon, termed a "regional polysterism", of these loop
      regions may be related with their multifunctionality: the GTP-dependent
      interactions with several downstream target groups such as the Raf and RalGDS
      families and also with the GTPase activating protein (GAP) family. In fact, the
      binding of Ras(1-171).GMPPNP with the Ras-binding domain (residues 51-131) of c
      Raf-1 was shown to eliminate the regional polysterism nearly completely. It was
      indicated, therefore, that each target/regulator selects its appropriate
      conformer among those presented by the "polysteric" binding interface of Ras. As
      the downstream target groups exhibit no apparent sequence homology to each other,
      it is possible that one target group prefers a conformer different from that
      preferred by another group. The involvement of loop L1 in the regional
      polysterism might suggest that the negative regulators, GAPs, bind to the
      polysteric binding interface (loops L2 and L4) of Ras and cooperatively select a
      conformer suitable for transition of the GTPase catalytic center, involving loops
      L1 and L4, into the highly active state.

PMID- 9230044
TI  - Refined structure, DNA binding studies, and dynamics of the bacteriophage Pf3
      encoded single-stranded DNA binding protein.
AB  - The solution structure of the 18-kDa single-stranded DNA binding protein encoded
      by the filamentous Pseudomonas bacteriophage Pf3 has been refined using 40 ms 15N
      and 13C-edited NOESY spectra and many homo- and heteronuclear J-couplings. The
      structures are highly precise, but some variation was found in the orientation of
      the beta-hairpin denoted the DNA binding wing with respect to the core of the
      protein. Backbone dynamics of the protein was investigated in the presence and
      absence of DNA by measuring the R1 and R2 relaxation rates of the 15N nuclei and
      the 15N-1H NOE. It was found that the DNA binding wing is much more flexible than
      the rest of the protein, but its mobility is largely arrested upon binding of the
      protein to d(A)6. This confirms earlier hypotheses on the role of this hairpin in
      the function of the protein, as will be discussed. Furthermore, the complete DNA
      binding domain of the protein has been mapped by recording two-dimensional TOCSY
      spectra of the protein in the presence and absence of a small amount of spin
      labeled oligonucleotide. The roles of specific residues in DNA binding were
      assessed by stoichiometric titration of d(A)6, which indicated for instance that
      Phe43 forms base stacking interactions with the single-stranded DNA. Finally, all
      results were combined to form a set of experimental restraints, which were
      subsequently used in restrained molecular dynamics calculations aimed at building
      a model for the Pf3 nucleoprotein complex. Implying in addition some similarities
      to the well-studied M13 complex, a plausible model could be constructed that is
      in accordance with the experimental data.

PMID- 9230045
TI  - The structure of L-aspartate ammonia-lyase from Escherichia coli.
AB  - The X-ray crystal structure of l-aspartate ammonia-lyase has been determined to
      2.8 A resolution. The enzyme contains three domains, and each domain is composed
      almost completely of alpha helices. The central domain is composed of five long
      helices. In the tetramer, these five helices form a 20-helix cluster. Such
      clusters have also been seen in delta-crystallin and in fumarase. The active site
      of aspartase has been located in a region that contains side chains from three
      different subunits. The structure of the apoenzyme has made it possible to
      identify some of the residues that are involved in binding the substrate. These
      residues have been examined by site-directed mutagenesis, and their putative
      roles have been assigned [Jayasekera, M. M. K., Shi, W., Farber, G. K., & Viola,
      R. E. (1997) Biochemistry 36, 9145-9150].

PMID- 9230046
TI  - Evaluation of functionally important amino acids in L-aspartate ammonia-lyase
      from Escherichia coli.
AB  - The high-resolution structure of l-aspartate ammonia-lyase from Escherichia coli
      has recently been determined [Shi, W., Dunbar, J., Jayasekera, M. M. K., Viola,
      R. E., & Farber, G. K. (1997) Biochemistry 36, 9136-9144]. An examination of the
      putative active site has been carried out, with the active site located in a
      cleft that contains the functionally significant lysine 327. A list of potential
      active site residues has been generated based on their proximity to this active
      site lysine, sequence homology comparisons with other members of the aspartase
      fumarase enzyme family, and the necessity for chemically reasonable
      functionalities for the proposed roles. The five most likely candidates in the
      putative active site cleft have been examined by site-directed mutagenesis to
      test their feasibility for either substrate binding or acid-base catalytic roles.
      Arginine and lysine residues have been identified that appear to function in the
      orientation and binding of aspartic acid at the enzyme active site. Some
      tentative assignments have also been made of the acid and base catalytic groups
      that are proposed to be involved in the deamination reaction.

PMID- 9230047
TI  - Phosphorylation and regulation of the Na+/H+ exchanger through mitogen-activated
      protein kinase.
AB  - We examined mitogen-activated protein kinase-mediated phosphorylation and
      activation of the Na+/H+ exchanger isoform type 1. A rabbit skeletal muscle
      extract was fractionated by FPLC chromatography. Four main fractions had the
      ability to phosphorylate the carboxyl-terminal region of NHE1. Western blot
      analysis and immunoprecipitation showed that three of these were associated with
      MAP kinase-dependent phosphorylation. Phosphorylation studies using purified MAP
      kinase showed that the region involved was the carboxyl-terminal 178 amino acids
      of the protein and that the stoichiometry was 1 phosphate/mol of protein. In-gel
      kinase assays showed that cytosolic extracts from smooth muscle cells also
      phosphorylate the carboxyl-terminal of NHE1 and that the MAP kinase-dependent
      phosphorylation could be activated by PDGF and AngII. Mutant cell lines with an
      inducible dominant negative MAP kinase showed decreased serum activation of
      Na+/H+ exchange but normal hypertonic activation of the protein. The results show
      that MAP kinase is intimately involved in regulation of the Na+/H+ exchanger,
      possibly through phosphorylation of one amino acid of the carboxyl-terminal
      cytosolic domain.

PMID- 9230048
TI  - Inhibition of preprotein translocation and reversion of the membrane inserted
      state of SecA by a carboxyl terminus binding mAb.
AB  - SecA is the peripheral subunit of the preprotein translocase of Escherichia coli.
      SecA consists of two independently folding domains, i.e., the N-domain bearing
      the high-affinity nucleotide binding site (NBS-I) and the C-domain that harbors
      the low-affinity NBS-II. ATP induces SecA insertion into the membrane during
      preprotein translocation. Domain-specific monoclonal antibodies (mAbs) were
      developed to analyze the functions of the SecA domains in preprotein
      translocation. The antigen binding sites of the obtained mAbs were confined to
      five epitopes. One of the mAbs, i.e., mAb 300-1K5, recognizes an epitope in the C
      domain in a region that has been implicated in membrane insertion. This mAb,
      either as IgG or as Fab, completely inhibits in vitro proOmpA translocation and
      SecA translocation ATPase activity. It prevents SecA membrane insertion and, more
      strikingly, reverses membrane insertion and promotes the release of SecA from the
      membrane. Surface plasmon resonance measurements demonstrate that the mAb
      recognizes the ADP- and the AMP-PNP-bound state of SecA either free in solution
      or bound at the membrane at the SecYEG protein. It is concluded that the mAb
      actively reverses a conformation essential for membrane insertion of SecA. The
      other mAbs directed to various epitopes in the N-domain were found to be without
      effect, although all bind the native SecA. These results demonstrate that the C
      domain plays an important role in the SecA membrane insertion, providing further
      evidence that this process is needed for preprotein translocation.

PMID- 9230049
TI  - Conformational changes in cholera toxin B subunit-ganglioside GM1 complexes are
      elicited by environmental pH and evoke changes in membrane structure.
AB  - Fluorescence resonance energy transfer (FRET) was used to monitor pH-dependent
      structural changes in the cholera toxin B subunit (CTB) and the membranes with
      which CTB associates. The distance separating the single tryptophan (Trp88) of
      each CTB monomer and a pyrene probe linked to the membrane-imbedded tail of
      ganglioside GM1 is not influenced by pH in a range from 3.5 to 7.5, consistent
      with the position of Trp88 in the GM1 binding site of CTB. In contrast, the
      distance between the pyrene probe on GM1 and coumarin, stilbene, or fluorescein
      probes covalently linked to specific sites on CTB appears to increase
      significantly as the pH is lowered to 5.0 or less. This conformational change is
      not accompanied by detectable changes in the distance between Trp88 and these
      extrinsic probe positions in the presence of nonfluorescent GM1. However, when
      the distance from Trp88 to the extrinsic probes is monitored as a function of pH
      in the absence of GM1, a conformational change is seen which indicates that
      receptor binding influences the character of pH-dependent conformational changes
      that occur within CTB. Interestingly, the observed change in CTB conformation is
      accompanied by a change in the relative position of GM1 within the membrane as
      judged by FRET from the pyrene probe on GM1 to a 7-nitrobenz-2-oxa-1,3-diazol-4
      yl (NBD) probe linked to the polar head group of phosphatidylethanolamine and
      positioned at the membrane surface. Taken together, the data imply that low
      endosomal pH is capable of inducing structural changes in CTB, which, in turn,
      exert effects on the structure of the membrane to which CTB is bound. These
      phenomena may have a role in (1) processing of cholera toxin within the endosomal
      compartments of some target cell types, (2) determining the lag time between
      cholera toxin binding and the target cell response to cholera intoxication, or
      (3) the efficiency of CTB and cholera toxin as mucosal adjuvants.

PMID- 9230050
TI  - Differential scanning calorimetry and CD spectrometry of acclimation temperature
      associated types of carp light meromyosin.
AB  - Differential scanning calorimetry and CD spectrometry were employed to study the
      thermal unfolding of light meromyosin (LMM) prepared from carp acclimated to
      different temperatures. The transition temperatures given by the major peaks at
      pH 8.0 in 0.6 M KCl for LMM from carp acclimated to 10 degrees C were 32.5 and
      39.5 degrees C with the calorimetric enthalpies (DeltaHcal) of 269 and 52
      kcal/mol, respectively. LMM from carp acclimated to 20 degrees C exhibited three
      peaks of transition temperatures at 34.5, 40.2, and 46.9 with DeltaHcal of 152,
      20, and 10 kcal/mol, respectively. On the other hand, LMM from carp acclimated to
      30 degrees C showed two different patterns. The first experiment gave two
      transition temperatures at 39.2 and 47.3 degrees C with DeltaHcal of 231 and 39
      kcal/mol, respectively. The second series of experiments resulted in showing
      three peaks of 34.4, 39.5, and 47.5 degrees C with DeltaHcal of 117, 123, and 28
      kcal/mol, respectively. N-terminal amino acid sequence analysis revealed that LMM
      at the second series of experiments with the 30 degrees C-acclimated carp
      contained component(s) predominant in the 20 degrees C-acclimated carp. Thermal
      unfolding responsible for these transition temperatures was well explained by
      melting of alpha-helices which could be determined by far-ultraviolet CD
      spectroscopy. These results clearly demonstrate that the 30 degrees C-acclimated
      carp contained the most thermostable LMM.

PMID- 9230051
TI  - Molecular basis for the coupling ion selectivity of F1F0 ATP synthases: probing
      the liganding groups for Na+ and Li+ in the c subunit of the ATP synthase from
      Propionigenium modestum.
AB  - The conserved glutamate residue at position 65 of the Propionigenium modestum c
      subunit is directly involved in binding and translocation of Na+ across the
      membrane. The site-specific introduction of the cQ32I and cS66A substitutions in
      the putative vicinity to cE65 inhibited growth of the single-site mutants on
      succinate minimal agar, indicating that both amino acid residues are important
      for proper function of the oxidative phosphorylation system. This growth
      inhibition was abolished, however, if the cF84L/cL87V double mutation was
      additionally present in the P. modestum c subunit. The newly constructed
      Escherichia coli strain MPC848732I, harboring the cQ32I/cF84L/cL87V triple
      mutation, revealed a change in the coupling ion specificity from Na+ to H+. ATP
      hydrolysis by this enzyme was therefore not activated by NaCl, and ATP-driven H+
      transport was not affected by this alkali salt. Both activities were influenced,
      however, by LiCl. These data demonstrate the loss of the Na+ binding site and
      retention of Li+ and H+ binding sites within this mutant ATPase. In the E. coli
      strain MPC848766A (cS66A/cF84L/cL87V), the specificity of the ATPase was further
      restricted to H+ as the exclusive coupling ion. Therefore, neither Na+ nor Li+
      stimulated the ATPase activity, and no ATP-driven Li+ transport was observed. The
      ATPase of the E. coli mutant MPC32N (cQ32N) was activated by NaCl and LiCl. The
      mutant ATPase exhibited a 5-fold higher Km for NaCl but no change in the Km for
      LiCl in comparison to that of the parent strain. These results demonstrate that
      the binding of Na+ to the c subunit of P. modestum requires liganding groups
      provided by Q32, E65, and S66. For the coordination of Li+, two liganding
      partners, E65 and S66, are sufficient, and H+ translocation was mediated by E65
      alone.

PMID- 9230052
TI  - Preferential solvation changes upon lysozyme heat denaturation in mixed solvents.
AB  - On the basis of scanning microcalorimetry data from literature and our own
      measurements, we have calculated the changes in preferential solvation of
      lysozyme upon heat denaturation in six solvent systems: water + methanol,
      ethanol, propanol [data from Velicelebi, G., & Sturtevant, J. M. (1979)
      Biochemistry 18, 1180], acetone, p-dioxane [data from Fujita, Y., & Noda, Y.
      (1983) Bull. Chem. Soc.Jpn. 56, 233], and dimethylsulfoxide [our data Kovrigin,
      E. L., Kirkitadze, M. D., & Potekhin, S. A. (1996) Biofizika 41, 549-553;
      Kovrigin, E. L., & Potekhin, S. A. (1996) Biofizika 41, 1201-1206]. These
      preferential solvation changes are (in effect) the numbers of cosolvent molecules
      entering or leaving the solvation shell of the protein upon denaturation. It has
      been shown that for a group of five substances in the initial activity range
      (approximately up to 0. 3) the denaturational changes of preferential solvation
      of lysozyme do not depend on the nature of the solvent and depend only on its
      activity. This suggests that lysozyme does not distinguish these substances in
      the initial activity range and preferential solvation has a nonspecific
      character. It has been shown also that preferential solvation DeltaGamma23 does
      not depend on the pH value at least for dimethylsulfoxide-water solutions. This
      indicates that the chargeable groups exposed on denaturation do not contribute
      significantly to preferential interaction of the protein surface with the
      solution components.

PMID- 9230053
TI  - Laser temperature jump study of the helix<==>coil kinetics of an alanine peptide
      interpreted with a 'kinetic zipper' model.
AB  - The kinetics of the helix<==>coil transition of an alanine-based peptide
      following a laser-induced temperature jump were monitored by the fluorescence of
      an N-terminal probe, 4-(methylamino)benzoic acid (MABA). This probe forms a
      peptide hydrogen bond to the helix backbone, which changes its fluorescence
      quantum yield. The MABA fluorescence intensity decreases in a single exponential
      relaxation, with relaxation times that are weakly temperature dependent,
      exhibiting a maximum value of approximately 20 ns near the midpoint of the
      melting transition. We have developed a new model, the kinetic version of the
      equilibrium 'zipper' model for helix<==>coil transitions to explain these
      results. In this 'kinetic zipper' model, an enormous reduction in the number of
      possible species results from the assumption that each molecule contains either
      no helical residues or a single contiguous region of helix (the single-sequence
      approximation). The decay of the fraction of N-terminal residues that are
      helical, calculated from numerical solutions of the kinetic equations which
      describe the model, can be approximately described by two exponential relaxations
      having comparable amplitudes. The shorter relaxation time results from rapid
      unzipping (and zipping) of the helix ends in response to the temperature jump,
      while the longer relaxation time results from equilibration of helix-containing
      and non-helix-containing structures by passage over the nucleation free energy
      barrier. The decay of the average helix content is dominated by the slower
      process. The model therefore explains the experimental observation that
      relaxation for the N-terminal fluorescent probe is approximately 8-fold faster
      than that for the infrared probe of Williams et al. [(1996) Biochemistry 35, 691
      697], which measures the average helix content, but does not account for the
      absence of observable amplitude for the slow relaxation in the fluorescence
      experiments (<10% slow phase). If we assume that the activation barrier for the
      coil-->helix rate is purely entropic, the model can also explain the maximum in
      the temperature dependence of the relaxation time for the fluorescent probe.
      Parameters that best reproduce the melting curves and the ratio of relaxation
      times predict a value of the cooperativity parameter sigma which is approximately
      3-fold larger than previously reported values obtained from fitting equilibrium
      data only. The helix growth rate of approximately 10(8) s-1 that reproduces the
      experimental relaxation times is approximately 100-fold slower than those
      observed in molecular dynamics simulations. These parameters can be used to
      simulate the kinetically cooperative formation of a helix from the all-coil
      state.

PMID- 9230054
TI  - Mitosene-DNA adducts. Characterization of two major DNA monoadducts formed by
      1,10-bis(acetoxy)-7-methoxymitosene upon reductive activation.
AB  - Reductive activation of racemic 1,10-bis(acetoxy)-7-methoxymitosene WV15 in the
      presence of DNA, followed by enzymatic digestion and HPLC analysis, revealed the
      formation of various DNA adducts. Reduction is a necessary event for adduct
      formation to occur. This reductive activation was performed under hypoxic
      conditions in various ways: (1) chemically, using a 2-fold excess of sodium
      dithionite (Na2S2O4), (2) enzymatically using NADH-cytochrome c reductase, (3)
      electrochemically on a mercury pool working electrode, and (4) catalytically,
      using a H2/PtO2 system. Five different mitosene-DNA adducts were detected. These
      adducts were also present when poly(dG-dC) was used instead of DNA, but were
      absent with poly(dA-dT). All were shown to be adducts of guanine. Reduction of 1,
      10-dihydroxymitosene WV14 in the presence of DNA did not result in detectable
      adduct formation, demonstrating the importance of good leaving groups for
      efficient adduct formation by these mitosenes. Finally, two of the adducts were
      isolated and their structures elucidated, using mass spectrometry, 1H NMR and
      circular dichroism (CD). The structures were assigned as the diastereoisomers N2
      (1"-n-hydroxymitosen-10"-yl), 2'-deoxyguanosine (n = alpha or beta). These type
      of adducts, in which the mitosene C-10 is covalently bonded to the N-2 of a
      guanosylic group, are different from the well-known mitomycin C 2'-deoxyguanosine
      monoadducts, that is linked via the mitomycin C C-1 position, demonstrating that
      the order of reactivity of the C-1 and C-10 in these mitosenes is reversed, as
      compared to mitomycin C. The 7-methoxy substituent of WV15 is a likely factor
      causing this switch. Evidence is presented that the 7-substituent of mitosenes
      also influences their DNA alkylation site. Adducts 4 and 5 represent the first
      isolated and structurally characterized covalent adducts of DNA and a synthetic
      mitosene.

PMID- 9230055
TI  - Ultraspiracle, a Drosophila retinoic X receptor alpha homologue, can mobilize the
      human thyroid hormone receptor to transactivate a human promoter.
AB  - We have analyzed the functional domains of the Drosophila orphan receptor
      Ultraspiracle (usp), a homologue of the vertebrate retinoic X receptor alpha, as
      well as the ability of heterodimers between usp and the thyroid hormone receptor
      beta (T3Rbeta) to transactivate the human apolipoprotein A-II (apoA-II) promoter.
      DNA binding assays demonstrated that heterodimers of usp and the human T3Rbeta
      can bind to the hormone response element (HRE) of the regulatory element AIIJ (
      734 to -716) of the human apoA-II promoter. Cotransfection experiments have shown
      that the combination of usp and T3Rbeta can transactivate the human apoA-II
      promoter in COS-1 cells 7-8-fold in the presence of thyroid hormone (T3). The
      observed transactivation was not affected by the deletion of the amino-terminal
      residues 1-85 of usp, which represent a putative transactivation domain,
      suggesting that the function of usp is to recruit T3Rbeta. Furthermore, a mutant
      usp, with impaired DNA binding properties, can form heterodimers with T3Rbeta in
      vitro but has reduced ability to transactivate the human apoA-II promoter. A
      minimal thymidine kinase (tk) promoter driven by four AIIJ regulatory elements is
      repressed to 20% of its original activity by T3Rbeta and the repression is
      relieved by usp/T3Rbeta heterodimers. Deletion analysis demonstrated that factors
      bound to the regulatory elements AIIJ, AIIAB, and AIIH participate in the
      usp/T3Rbeta-mediated transactivation of the human apoA-II promoter. Similarly to
      element AIIJ, element AIIAB binds usp/T3Rbeta heterodimers, whereas element AIIH
      binds a COS-1 nuclear activity that is supershifted with anti-hepatic nuclear
      factor 1 antibodies. The findings suggest that optimal transactivation of the
      apoA-II promoter by usp/T3Rbeta heterodimers requires complex interactions
      between these heterodimers and factors bound to other regulatory elements. The
      observed transcriptional activation through heterodimer formation between nuclear
      receptors from species as divergent in the evolutionary scale as insects and
      mammals indicates that the functional domains of these proteins have been highly
      conserved.

PMID- 9230056
TI  - Lipid domains in the membrane: thermotropic properties of sphingomyelin vesicles
      containing GM1 ganglioside and cholesterol.
AB  - The thermotropic behavior of palmitoylsphingomyelin vesicles containing GM1
      ganglioside and cholesterol has been investigated by high-sensitivity
      differential scanning calorimetry. The thermograms exhibited by binary
      palmitoylsphingomyelin/GM1 mixtures are resolvable into two components. The
      relative contribution of the minor component, undetectable in the absence of
      ganglioside, to the total enthalpy and its transition temperature (>40 degrees C)
      increase with the concentration of the glycolipid embedded in the vesicles. These
      data suggest the occurrence of lateral phase separation and that more ordered,
      higher melting GM1 ganglioside-enriched domains are present within the
      sphingomyelin bilayer. Studies on binary sphingomyelin/cholesterol mixtures
      confirmed the known tendency of the sterol to decrease the total enthalpy of
      sphingomyelin, forming cholesterol-enriched domains. The thermograms exhibited by
      ternary sphingomyelin/ganglioside/cholesterol mixtures in variable proportions
      (up to 20% molar GM1 or Chol) displayed, on increasing the content of either the
      sterol or the ganglioside, features addressable to sphingomyelin/cholesterol
      (peaks centered at temperature </=40 degrees C, decrease of enthalpy) or to
      sphingomyelin/GM1 mixtures (peaks centered at a temperature >40 degrees C),
      respectively. This trend was confirmed by deconvolution analysis, showing that
      the thermograms are resolvable into components addressable to GM1-enriched and to
      cholesterol-enriched domains. Taken all together, the results show that the
      architectural features of sphingomyelin bilayers are strongly dependent on the
      presence of GM1 ganglioside and cholesterol, whose presence is leading to the
      formation of separate, GM1-enriched and cholesterol-enriched distinct domains.
      Ganglioside-sphingomyelin and sphingomyelin-cholesterol, together with mutual
      ganglioside-ganglioside, interactions could contribute to maintain a network of
      bonds extending to proteins, forming specialized membrane domains, such as
      caveolae, or others, whose experimental clues are the glycolipid-enriched
      detergent-insoluble fractions that can be isolated from cell membranes.

PMID- 9230057
TI  - Role of lipids in the permeabilization of membranes by class L amphipathic
      helical peptides.
AB  - We studied the mechanism of membrane permeabilization by the 18L model peptide
      (GIKKFLGSIWKFIKAFVG), which features the consensus class L sequence averaged from
      the number of naturally occurring lytic peptides. Two aspects of membrane lipid
      composition significantly affected peptide-membrane interactions: the presence of
      acidic lipids and, in zwitterionic membranes, and the presence of nonbilayer
      forming lipids. In zwitterionic membranes, 18L peptide destabilizes the membrane,
      leading to a transient formation of large defects in the membrane which result
      generally in contents leakage, but in the presence of bilayer-bilayer contact can
      alternatively lead to vesicle fusion. In membranes containing acidic lipids
      (DOPC:DOPG, DOPG), 18L caused leakage but not fusion, probably due to mutual
      repulsion of acidic vesicles. While the extent of contents leakage was
      approximately the same as for zwitterionic membranes, the kinetics of leakage
      could be resolved only by using stopped-flow, leakage being essentially complete
      within the first minute. Previously, we reported that apolipoprotein (class A)
      and lytic (class L) peptide analogs have opposing effects on some properties of
      biological membranes. This reciprocal effect of 18L and Ac-18A-NH2, class A model
      peptide, is restricted to membranes with a high propensity for nonbilayer phase
      formation (DOPE, Me-DOPE, DOPC:DOPE, DOPC:Me-DOPE). The decrease in the content
      of nonbilayer phase forming lipid or the addition of acidic lipids reduces or
      eliminates the reciprocal effects. This suggests the importance of nonbilayer
      phase propensity for certain functions of biological membranes.

PMID- 9230058
TI  - Yeast protein farnesyltransferase. Site-directed mutagenesis of conserved
      residues in the beta-subunit.
AB  - Protein prenyltransferases catalyze the posttranslational modification of
      cysteines by isoprenoid hydrocarbon chains. A protein farnesyltransferase
      (PFTase) and a protein geranylgeranyltransferase (PGGTase-I) alkylate cysteines
      in a CaaX C-terminal tetrapeptide sequence, where a is usually an aliphatic amino
      acid and X is an amino acid that specifies whether a C15 farnesyl or C20
      geranylgeranyl moiety is added. A third enzyme, PGGTase-II, adds geranylgeranyl
      groups to both cysteines at the C-terminus of Rab proteins. All three enzymes are
      Zn2+ metalloproteins and also require Mg2+ for activity. The protein
      prenyltransferases are heterodimers. PFTase and PGGTase I contain identical alpha
      subunits and distinctive beta-subunits, which are responsible for the differences
      in substrate selectivity seen for the two enzymes. The subunits in PGGTase-II are
      similar, but not identical, to their counterparts in the other two enzymes. An
      alignment of amino acid sequences for the beta-subunits of all three enzymes
      shows five regions of high similarity. Thirteen of the conserved polar and
      charged residues in yeast PFTase were selected for substitution by site-directed
      mutagenesis. Kinetic studies revealed a subset of five enzymes, R211Q, D307A,
      C309A, Y310F, and H363A, with substantially reduced catalytic constants (kcat).
      Metal analyses of wild-type enzyme and the five least reactive mutants showed
      that the substitutions had compromised Zn2+ binding in the D307A, C309A, and
      H363A enzymes.

PMID- 9230059
TI  - Functional differences in the interaction of arrestin and its splice variant,
      p44, with rhodopsin.
AB  - Arrestin quenches signal transduction in rod photoreceptors by blocking the
      catalytic activity of photoactivated phosphorylated rhodopsin toward the G
      protein, transducin (Gt). Rod cells also express a splice variant of arrestin,
      termed p44, in which the last 35 amino acids are replaced by a single Ala. In
      contrast to arrestin, this protein has been reported to bind to both the
      phosphorylated and nonphosphorylated forms of the activated receptor. In this
      study, we analyzed formation of the rhodopsin-p44 complex in vitro. Like
      arrestin, p44 stabilized the meta II (MII) photoproduct relative to forms MI and
      MIII and did not interact measurably with the apoprotein opsin. However, several
      differences between p44 and its parent protein were found: (i) p44 binds to
      nonphosphorylated MII with a much lower affinity (KD = 0.24 microM) than to
      phosphorylated MII (P-MII) (KD = 12 nM); arrestin binds only to P-MII (KD = 20
      nM); (ii) p44 interacted also with truncated MII (329G-Rho MII), which lacked the
      sites of phosphorylation; (iii) with both MII and P-MII, the activation energy of
      complex formation with p44 was lower than that found for arrestin (70 kJ/mol
      instead of 140 kJ/mol); and (iv) InsP6 inhibited poorly the interaction between
      p44 and P-MII, but it strongly inhibited the interaction between arrestin and P
      MII. Extrapolation of the measured on-rates to physiological conditions yielded
      reaction times for the binding of p44 to activated rhodopsin. The data suggest
      that the splice variant, p44, and its parent protein, arrestin, play different
      roles in phototransduction. The physiological significance of these differences
      remains to be determined.

PMID- 9230060
TI  - Low-temperature interactions of NO with the S1 and S2 states of the water
      oxidizing complex of photosystem II. A novel Mn-multiline EPR signal derived from
      the S1 state.
AB  - The spin-1/2-carrying NO molecule interacts with both the S1 and S2 states of the
      water oxidizing complex. The intermediates of the interaction can be resolved and
      trapped by NO treatment at subzero temperatures. At -30 degrees C and in the
      presence of approx. 500-700 microM NO, S1 loses the ability to yield by
      illumination an EPR active S2-state with an approximate half-time of 40-60 min.
      At longer incubation times (t1/2 = 4-5 h), an intense new multiline signal
      develops. The new signal has a hyperfine splitting similar to the S2 multiline
      [Dismukes, G. C., & Siderer, Y. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 274
      278], but a modified shape with intense lines on the high field side. The NO
      modified S1 state can act as a low-temperature electron donor yielding an EPR
      silent state upon illumination at 200 K. NO interacts also with the S2 state of
      the water oxidizing complex rapidly at temperatures as low as -75 degrees C, to
      yield an EPR silent state. The rates of the latter interaction show analogies to
      the ammonia binding to the S2 state. It is possible, however, that NO, unlike
      ammonia, destabilizes the S2 state. On the basis of preliminary experiments with
      varying chloride concentrations in the range 0.1-50 mM, the S1 multiline state is
      attributed to binding of NO at a chloride sensitive site on the Mn cluster. The
      rapid interactions with the S2 state as well as the intermediate binding to the
      S1 state are less well understood at present, but they are tentatively assigned
      to the chloride-insensitive site of ammonia binding in the Mn cluster.

PMID- 9230061
TI  - Viscosity dependence of the electron transfer rate from bound cytochrome c to
      P840 in the photosynthetic reaction center of the green sulfur bacterium
      Chlorobium tepidum.
AB  - Anomalous high viscosity dependence was found in the rate of reaction between the
      bound cytochrome c and the primary donor bacteriochlorophyll dimer (P840) of the
      reaction center complex purified from the green sulfur bacterium Chlorobium
      tepidum. The cytochrome has a primary structure with the N-terminal three
      membrane-spanning helices connected to the extended C-terminal heme-containing
      hydrophilic moiety. The rate constant of the reaction decreased from 5.0 x 10(3)
      s-1 to 1.0 x 10 s-1 as the glycerol concentration increased from 0 to 60% (v/v)
      at 295 K, showing a linear dependence on the -2.4th power of the specific
      viscosity. The glycerol effect was fully reversible. The extraordinary high
      viscosity dependence cannot be explained by the simple diffusive Brownian
      fluctuation model and suggests that the electron transfer mechanism is dependent
      on the unique conformational fluctuations of the heme-containing moiety of
      cytochrome c.

PMID- 9230062
TI  - Reconstitution of the holoenzyme form of Escherichia coli porphobilinogen
      deaminase from apoenzyme with porphobilinogen and preuroporphyrinogen: a study
      using circular dichroism spectroscopy.
AB  - Porphobilinogen deaminase (PBG-D), an early enzyme of the tetrapyrrole
      biosynthetic pathway, catalyzes the formation of a tetrapyrrole chain,
      preuroporphyrinogen, from four molecules of porphobilinogen (PBG). The PBG-D
      apoenzyme is responsible for the autocatalytic synthesis and covalent attachment
      of a dipyrromethane cofactor at its active site. In this paper an efficient
      method for the purification of Escherichia coli PBG-D apoenzyme using an affinity
      chromatography resin is reported. Circular dichroism (CD) spectra of apoenzyme
      and holoenzyme were recorded and significant differences in both the backbone and
      aromatic region of the spectra were observed. The differences in the spectra
      allowed the reconstitution of holoenzyme from purified apoenzyme with PBG and
      preuroporphyrinogen in solution to be monitored separately by CD. Apoenzyme
      incubated with preuroporhyrinogen gave a CD spectrum that was much more like the
      CD spectrum of holoenzyme than apoenzyme incubated with PBG. The results showed
      clearly that the cofactor was generated much more rapidly from
      preuroporphyrinogen than from PBG. Changes in the CD spectrum associated with the
      aromatic side-chain region, in particular the contribution assigned to
      phenylalanine-62, were found to correlate well with the activity of the
      reconstituted enzyme. Phenylalanine-62 is located in close proximity to the
      cofactor and acts as a sensitive probe to active-site changes. The stability of
      the holoenzyme and apoenzyme were compared with respect to both heat and
      susceptibility to proteolysis. The results were consistent with a model for the
      apoenzyme in which, in the absence of the cofactor, the three domains of the
      protein are held less rigidly together, thereby making the protein more
      susceptible to heat denaturation and proteolysis. The CD spectrum of the
      holoenzyme was found to be similar at both pH 5.1 and 7.4, suggesting that the
      crystal structure, determined at pH 5.1, is likely to be similar at physiological
      pH values.

PMID- 9230063
TI  - Apoptosis in tumorigenesis and cancer therapy.
AB  - Apoptosis is a morphologically and biochemically distinct form of cell death
      which can be triggered by a variety of extracellular agents during both normal
      development as well as in adult pathological states. Much progress has recently
      been made in understanding the molecular pathways which regulate this process as
      well as new intersections between these. A direct interaction between components
      of the 'executioner'--the ICE-family of cysteine proteases--and the Bcl-2 family
      of proteins, which modulate a cell's propensity to undergo apoptosis, has
      recently been demonstrated. New pathways to cell survival, like the PI3-K/Akt
      signal transduction pathway, are also providing new clues as to the regulation of
      cell death by growth factors and extracellular matrix for example. The links
      which exist between apoptosis and cancer research are several. Genetic
      alterations in components of the apoptosis pathway occur during tumorigenesis and
      confer resistance to a variety of physiological (oncogene-induced cell death,
      loss of adhesion, growth under hypoxia) as well as therapeutic (chemotherapy and
      radiation) death triggers. Similarly, antineoplastic therapies are thought to
      induce tumor cell apoptosis, and consequently, common mutations in apoptosis
      regulatory genes carry a poor prognosis for the patient. A more detailed
      understanding of the biochemistry of apoptosis and the ways in which it is
      disabled in tumors will likely reveal new transformation selective death triggers
      which stimulate cell death in ways independent of components like p53 and
      increase the therapeutic window of these drugs in the clinics.

PMID- 9230064
TI  - Leukotriene C4 synthase: a critical enzyme for the biosynthesis of SRS-A.
AB  - Leukotriene (LT) C4 synthase catalyzes the conjugation of LTA4 with reduced
      glutathione (GSH) to form LTC4, the parent compound of cysteinyl leukotrienes. It
      is a 18 kDa protein that functions as homodimer. Cloning of LTC4 synthase cDNA
      reveals amino acid homology with 5-lipoxygenase activating protein (FLAP) and
      newly identified microsomal glutathione S-transferase II (mGST-II) but not with
      cytosolic GSTs or mGST-I. LTC4 synthase gene contains 5 exons and four introns.
      This gene has been localized to the long arm of human chromosome 5 at the region
      of 5q35 which is in close proximity to the cluster of genes that are involved in
      inflammation and asthma. Mutagenic studies reveals that amino acid residues Arg
      51 and Tyr-93 are critical for catalytic function. Arg-51 was proposed to open
      the epoxide ring of LTA4 and Tyr-93 to provide the thiolate anion of GSH.

PMID- 9230065
TI  - Pancreas transplantation: indications, clinical management, and outcomes.
AB  - Although many advances have been made, pancreas transplantation still poses
      several challenges to the surgeon, internist and patient. With success rates now
      above 80% and improving yearly, diabetic patients must make a major life-style
      decision when considering a pancreas transplant. The main concerns are will the
      benefits of insulin-independence off-set the risks of surgery and
      immunosuppression. For diabetics near dialysis and considering a kidney
      transplant, the decision may not be as difficult. However, for those patients who
      are failing insulin therapy (brittle control) and remain with good renal
      function, the options are limited. As the success of pancreas transplantation
      improves, the procedure may become routine at more centers and become accepted by
      more third-party carriers. However, as with other solid organs, the availability
      of pancreases is limited and the supply soon to be exhausted. Thus, further
      advances are required for the prevention and treatment of Type 1 diabetes.
      Hopefully, the new frontiers of the next century will allow physicians to
      identify and preventively treat those at risk for the development of diabetes.
      Thus, the population of patients suffering from the consequences of this dreadful
      disease will be greatly reduced. With new developments in immunosuppression and
      islet transplantation, diabetic patients of the future may be offered the option
      of a procedure with reduced risks, less morbidity, and improved long-term cure
      rates.

PMID- 9230066
TI  - Distinct tumor specific expression of TGFB4 (ebaf)*, a novel human gene of the
      TGF-beta superfamily.
AB  - We recently identified a novel gene of the TGF-beta superfamily, endometrial
      bleeding associated factor, TGFB4 (ebaf), that, throughout the menstrual cycle,
      exhibited a defined expression in human endometrium. Here, we report on the
      expression of TGFB4 (ebaf) in normal and neoplastic human tissues. The expression
      of this gene was absent in a host of normal tissues including lung, stomach,
      small bowel, liver, kidney, breast, lymph node, spleen, ovary and fallopian tube.
      However, a weak expression of the 2.1 kb variant of the TGFB4 (ebaf) mRNA was
      observed in rectal, ovarian, and testicular tissues and the 2.1 and 2.5 kb TGFB4
      (ebaf) mRNAs were observed in the pancreatic tissue. The expression of the mRNA
      of this gene was absent in sarcomas, Hodgkin's and non-Hodgkin's lymphomas,
      melanomas, squamous cell carcinomas, hepatocellular carcinomas, renal cell
      carcinomas, and adenocarcinomas of the breast, endometrium and lung. The
      expression of the TGFB4 (ebaf) mRNA was observed primarily in adenocarcinomas
      that exhibited a mucinous differentiation. This included colonic, duodenal, and
      ovarian adenocarcinomas. The expression of TGFB4 (ebaf) mRNA was absent in non-
      mucinous colonic, gastric and ovarian adenocarcinomas and adenocarcinomas of
      colon metastatic to the liver. However, some serous adenocarcinomas of the ovary
      also exhibited TGFB4 (ebaf) mRNA. The testicular tumors, seminomas and embryonal
      carcinomas, also expressed TGFB4 (ebaf) mRNA. These findings show that the TGFB4
      (ebaf) mRNA has distinct tumor specific expression.

PMID- 9230067
TI  - Role of the modular domains of SR proteins in subnuclear localization and
      alternative splicing specificity.
AB  - SR proteins are required for constitutive pre-mRNA splicing and also regulate
      alternative splice site selection in a concentration-dependent manner. They have
      a modular structure that consists of one or two RNA-recognition motifs (RRMs) and
      a COOH-terminal arginine/serine-rich domain (RS domain). We have analyzed the
      role of the individual domains of these closely related proteins in cellular
      distribution, subnuclear localization, and regulation of alternative splicing in
      vivo. We observed striking differences in the localization signals present in
      several human SR proteins. In contrast to earlier studies of RS domains in the
      Drosophila suppressor-of-white-apricot (SWAP) and Transformer (Tra) alternative
      splicing factors, we found that the RS domain of SF2/ASF is neither necessary nor
      sufficient for targeting to the nuclear speckles. Although this RS domain is a
      nuclear localization signal, subnuclear targeting to the speckles requires at
      least two of the three constituent domains of SF2/ASF, which contain additive and
      redundant signals. In contrast, in two SR proteins that have a single RRM (SC35
      and SRp20), the RS domain is both necessary and sufficient as a targeting signal
      to the speckles. We also show that RRM2 of SF2/ASF plays an important role in
      alternative splicing specificity: deletion of this domain results in a protein
      that, although active in alternative splicing, has altered specificity in 5'
      splice site selection. These results demonstrate the modularity of SR proteins
      and the importance of individual domains for their cellular localization and
      alternative splicing function in vivo.

PMID- 9230068
TI  - Xlrbpa, a double-stranded RNA-binding protein associated with ribosomes and
      heterogeneous nuclear RNPs.
AB  - We have cloned and characterized Xlrbpa, a double-stranded RNA-binding protein
      from Xenopus laevis. Xlrbpa is a protein of 33 kD and contains three tandemly
      arranged, double-stranded RNA-binding domains (dsRBDs) that bind exclusively to
      double-stranded RNA in vitro, but fail to bind either single-stranded RNA or DNA.
      Sequence data and the overall organization of the protein suggest that Xlrbpa is
      the Xenopus homologue of human TAR-RNA binding protein (TRBP), a protein isolated
      by its ability to bind to human immunodeficiency virus (HIV) TAR-RNA. In
      transfection assays, TRBP has also been shown to inhibit the interferon-induced
      protein kinase PKR possibly by direct physical interaction. To determine the
      function of Xlrbpa and its human homologue we studied the expression and
      intracellular distribution of the two proteins. Xlrbpa is ubiquitously expressed
      with marked quantitative differences amongst all tissues. Xlrbpa and human TRBP
      can be detected in the cytoplasm and nucleus by immunofluorescence staining and
      Western blotting. Sedimentation gradient analyses and immunoprecipitation
      experiments suggest an association of cytoplasmic Xlrbpa with ribosomes. In
      contrast, a control construct containing two dsRBDs fails to associate with
      ribosomes in microinjected Xenopus oocytes. Nuclear staining of Xenopus lampbrush
      chromosome preparations showed the association of the protein with nucleoli,
      again indicating an association of the protein with ribosomal RNAs. Additionally,
      Xlrbpa could be located on lampbrush chromosomes and in snurposomes.
      Immunoprecipitations of nuclear extracts demonstrated the presence of the protein
      in heterogeneous nuclear (hn) RNP particles, but not in small nuclear RNPs,
      explaining the chromosomal localization of the protein. It thus appears that
      Xlrbpa is a general double-stranded RNA-binding protein which is associated with
      the majority of cellular RNAs, ribosomal RNAs, and hnRNAs either alone or as part
      of an hnRNP complex.

PMID- 9230069
TI  - Plasma membrane translocation of fluorescent-labeled phosphatidylethanolamine is
      controlled by transcription regulators, PDR1 and PDR3.
AB  - The transcription regulators, PDR1 and PDR3, have been shown to activate the
      transcription of numerous genes involved in a wide range of functions, including
      resistance to physical and chemical stress, membrane transport, and organelle
      function in Saccharomyces cerevisiae. We report here that PDR1 and PDR3 also
      regulate the transcription of one or more undetermined genes that translocate
      endogenous and fluorescent-labeled (M-C6-NBD-PE) phosphatidylethanolamine across
      the plasma membrane. A combination of fluorescence microscopy, fluorometry, and
      quantitative analysis demonstrated that M-C6-NBD-PE can be translocated both
      inward and outward across the plasma membrane of yeast cells. Mutants, defective
      in the accumulation of M-C6-NBD-PE, were isolated by selectively photokilling
      normal cells that accumulated the fluorescent phospholipid. This led to the
      isolation of numerous trafficking in phosphatidylethanolamine (tpe) mutants that
      were defective in intracellular accumulation of M-C6-NBD-PE. Complementation
      cloning and linkage analysis led to the identification of the dominant mutation
      TPE1-1 as a new allele of PDR1 and the semidominant mutation tpe2-1 as a new
      allele of PDR3. The amount of endogenous phosphatidylethanolamine exposed to the
      outer leaflet of the plasma membrane was measured by covalent labeling with the
      impermeant amino reagent, trinitrobenzenesulfonic acid. The amount of outer
      leaflet phosphatidylethanolamine in both mutant strains increased four- to
      fivefold relative to the parent Tpe+ strain, indicating that the net inward flux
      of endogenous phosphatidylethanolamine as well as M-C6-NBD-PE was decreased.
      Targeted deletions of PDR1 in the new allele, PDR1-11, and PDR3 in the new
      allele, pdr3-11, resulted in normal M-C6-NBD-PE accumulation, confirming that
      PDR1-11 and pdr3-11 were gain-of-function mutations in PDR1 and PDR3,
      respectively. Both mutant alleles resulted in resistance to the drugs
      cycloheximide, oligomycin, and 4-nitroquinoline N-oxide (4-NQO). However, a
      previously identified drug-resistant allele, pdr3-2, accumulated normal amounts
      of M-C6-NBD-PE, indicating allele specificity for the loss of M-C6-NBD-PE
      accumulation. These data demonstrated that PDR1 and PDR3 regulate the net rate of
      M-C6-NBD-PE translocation (flip-flop) and the steady-state distribution of
      endogenous phosphatidylethanolamine across the plasma membrane.

PMID- 9230070
TI  - Regulation and function of the CD3gamma DxxxLL motif: a binding site for adaptor
      protein-1 and adaptor protein-2 in vitro.
AB  - Several receptors are downregulated by internalization after ligand binding.
      Regulation of T cell receptor (TCR) expression is an important step in T cell
      activation, desensitization, and tolerance induction. One way T cells regulate
      TCR expression is by phosphorylation/dephosphorylation of the TCR subunit
      clusters of differentiation (CD)3gamma. Thus, phosphorylation of CD3gamma serine
      126 (S126) causes a downregulation of the TCR. In this study, we have analyzed
      the CD3gamma internalization motif in three different systems in parallel: in the
      context of the complete multimeric TCR; in monomeric CD4/CD3gamma chimeras; and
      in vitro by binding CD3gamma peptides to clathrin-coated vesicle adaptor proteins
      (APs). We find that the CD3gamma D127xxxLL131/132 sequence represents one united
      motif for binding of both AP-1 and AP-2, and that this motif functions as an
      active sorting motif in monomeric CD4/ CD3gamma molecules independently of S126.
      An acidic amino acid is required at position 127 and a leucine (L) is required at
      position 131, whereas the requirements for position 132 are more relaxed. The
      spacing between aspartic acid 127 (D127) and L131 is crucial for the function of
      the motif in vivo and for AP binding in vitro. Furthermore, we provide evidence
      indicating that phosphorylation of CD3gamma S126 in the context of the complete
      TCR induces a conformational change that exposes the DxxxLL sequence for AP
      binding. Exposure of the DxxxLL motif causes an increase in the TCR
      internalization rate and we demonstrate that this leads to an impairment of TCR
      signaling. On the basis of the present results, we propose the existence of at
      least three different types of L-based receptor sorting motifs.

PMID- 9230071
TI  - A novel Rab9 effector required for endosome-to-TGN transport.
AB  - Rab9 GTPase is required for the transport of mannose 6-phosphate receptors from
      endosomes to the trans-Golgi network in living cells, and in an in vitro system
      that reconstitutes this process. We have used the yeast two-hybrid system to
      identify proteins that interact preferentially with the active form of Rab9. We
      report here the discovery of a 40-kD protein (p40) that binds Rab9-GTP with
      roughly fourfold preference to Rab9-GDP. p40 does not interact with Rab7 or K
      Ras; it also fails to bind Rab9 when it is bound to GDI. The protein is found in
      cytosol, yet a significant fraction (approximately 30%) is associated with
      cellular membranes. Upon sucrose density gradient flotation, membrane- associated
      p40 cofractionates with endosomes containing mannose 6-phosphate receptors and
      the Rab9 GTPase. p40 is a very potent transport factor in that the pure,
      recombinant protein can stimulate, significantly, an in vitro transport assay
      that measures transport of mannose 6-phosphate receptors from endosomes to the
      trans-Golgi network. The functional importance of p40 is confirmed by the finding
      that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy
      with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor
      transport. These data are consistent with a model in which p40 and Rab9 act
      together to drive the process of transport vesicle docking.

PMID- 9230072
TI  - Myosin II is involved in the production of constitutive transport vesicles from
      the TGN.
AB  - The participation of nonmuscle myosins in the transport of organelles and
      vesicular carriers along actin filaments has been documented. In contrast, there
      is no evidence for the involvement of myosins in the production of vesicles
      involved in membrane traffic. Here we show that the putative TGN coat protein
      p200 (Narula, N., I. McMorrow, G. Plopper, J. Doherty, K.S. Matlin, B. Burke, and
      J.L. Stow. 1992. J. Cell Biol. 114: 1113-1124) is myosin II. The recruitment of
      myosin II to Golgi membranes is dependent on actin and is regulated by G
      proteins. Using an assay that studies the release of transport vesicles from the
      TGN in vitro, we provide functional evidence that p200/myosin is involved in the
      assembly of basolateral transport vesicles carrying vesicular stomatitis virus G
      protein (VSVG) from the TGN of polarized MDCK cells. The 50% reduced efficiency
      in VSVG vesicle release from the TGN in vitro after depletion of p200/myosin II
      could be reestablished to control levels by the addition of purified nonmuscle
      myosin II. Several inhibitors of the actin-stimulated ATPase activity of myosin
      specifically inhibited the release of VSVG-containing vesicles from the TGN.

PMID- 9230073
TI  - Sphingolipid transport to the apical plasma membrane domain in human hepatoma
      cells is controlled by PKC and PKA activity: a correlation with cell polarity in
      HepG2 cells.
AB  - The regulation of sphingolipid transport to the bile canalicular apical membrane
      in the well differentiated HepG2 hepatoma cells was studied. By employing
      fluorescent lipid analogs, trafficking in a transcytosis-dependent pathway and a
      transcytosis-independent ('direct') route between the trans-Golgi network and the
      apical membrane were examined. The two lipid transport routes were shown to
      operate independently, and both were regulated by kinase activity. The kinase
      inhibitor staurosporine inhibited the direct lipid transport route but slightly
      stimulated the transcytosis-dependent route. The protein kinase C (PKC) activator
      phorbol-12 myristate-13 acetate (PMA) inhibited apical lipid transport via both
      transport routes, while a specific inhibitor of this kinase stimulated apical
      lipid transport. Activation of protein kinase A (PKA) had opposing effects, in
      that a stimulation of apical lipid transport via both transport routes was seen.
      Interestingly, the regulatory effects of either kinase activity in sphingolipid
      transport correlated with changes in cell polarity. Stimulation of PKC activity
      resulted in a disappearance of the bile canalicular structures, as evidenced by
      the redistribution of several apical markers upon PMA treatment, which was
      accompanied by an inhibition of apical sphingolipid transport. By contrast,
      activation of PKA resulted in an increase in the number and size of bile
      canaliculi and a concomitant enhancement of apical sphingolipid transport. Taken
      together, our data indicate that apical membrane-directed sphingolipid transport
      in HepG2 cells is regulated by kinases, which could play a role in the biogenesis
      of the apical plasma membrane domain.

PMID- 9230074
TI  - Thrombin stimulates glucose transport in human platelets via the translocation of
      the glucose transporter GLUT-3 from alpha-granules to the cell surface.
AB  - Increased energy metabolism in the circulating blood platelet plays an essential
      role in platelet plug formation and clot retraction. This increased energy
      consumption is mainly due to enhanced anaerobic consumption of glucose via the
      glycolytic pathway. The aim of the present study was to determine the role of
      glucose transport as a potential rate-limiting step for human platelet glucose
      metabolism. We measured in isolated platelet preparations the effect of thrombin
      and ADP activation, on glucose transport (2-deoxyglucose uptake), and the
      cellular distribution of the platelet glucose transporter (GLUT), GLUT-3.
      Thrombin (0.5 U/ml) caused a pronounced shape change and secretion of most alpha
      granules within 10 min. During that time glucose transport increased
      approximately threefold, concomitant with a similar increase in expression of
      GLUT-3 on the plasma membrane as observed by immunocytochemistry. A major shift
      in GLUT-3 labeling was observed from the alpha-granule membranes in resting
      platelets to the plasma membrane after thrombin treatment. ADP induced shape
      change but no significant alpha-granule secretion. Accordingly, ADP-treated
      platelets showed no increased glucose transport and no increased GLUT-3 labeling
      on the plasma membrane. These studies suggest that, in human blood platelets,
      increased energy metabolism may be precisely coupled to the platelet activation
      response by means of the translocation of GLUT-3 by regulated secretion of alpha
      granules. Observations in megakaryocytes and platelets freshly fixed from blood
      confirmed the predominant GLUT-3 localization in alpha-granules in the isolated
      cells, except that even less GLUT-3 is present at the plasma membrane in the
      circulating cells (approximately 15%), indicating that glucose uptake may be
      upregulated five to six times during in vivo activation of platelets.

PMID- 9230075
TI  - Fusion competence of myoblasts rendered genetically null for N-cadherin in
      culture.
AB  - Myoblast fusion is essential to muscle tissue development yet remains poorly
      understood. N-cadherin, like other cell surface adhesion molecules, has been
      implicated by others in muscle formation based on its pattern of expression and
      on inhibition of myoblast aggregation and fusion by antibodies or peptide mimics.
      Mice rendered homozygous null for N-cadherin revealed the general importance of
      the molecule in early development, but did not test a role in skeletal
      myogenesis, since the embryos died before muscle formation. To test genetically
      the proposed role of N-cadherin in myoblast fusion, we successfully obtained N
      cadherin null primary myoblasts in culture. Fusion of myoblasts expressing or
      lacking N-cadherin was found to be equivalent, both in vitro by intracistronic
      complementation of lacZ and in vivo by injection into the muscles of adult mice.
      An essential role for N-cadherin in mediating the effects of basic fibroblast
      growth factor was also excluded. These methods for obtaining genetically
      homozygous null somatic cells from adult tissues should have broad applications.
      Here, they demonstrate clearly that the putative fusion molecule, N-cadherin, is
      not essential for myoblast fusion.

PMID- 9230076
TI  - The mesodermal expression of rolling stone (rost) is essential for myoblast
      fusion in Drosophila and encodes a potential transmembrane protein.
AB  - In homozygous rolling stone embryos, the fusion of myoblasts to syncytial
      myotubes is diminished. Nevertheless, the visceral mesoderm, the heart mesoderm,
      and few somatic muscles are properly formed. Thus, we postulate a central role of
      rolling stone for the fusion process within the somatic mesoderm. We have cloned
      the rolling stone gene, and the deduced protein sequence is in accordance with a
      transmembrane protein, which agrees with the enrichment of Rost in the membrane
      fraction of Drosophila embryos. No homologous genes have been described so far.
      rolling stone is expressed in the embryonic nervous system and cells of the
      somatic mesoderm, most notable in muscle founder cells. To elucidate the function
      of rolling stone for myoblast fusion, we applied a knock-out strategy. The
      expression of an antisense rolling stone transcript specifically within the
      mesoderm of wild-type embryos results in fusion defects of myoblasts, proving
      that the rolling stone expression in the mesoderm is responsible for the rolling
      stone phenotype. We suggest that rolling stone is a member of a group of genes
      that are necessary for the fusion process during myogenesis.

PMID- 9230077
TI  - Talin-null cells of Dictyostelium are strongly defective in adhesion to particle
      and substrate surfaces and slightly impaired in cytokinesis.
AB  - Dictyostelium discoideum contains a full-length homologue of talin, a protein
      implicated in linkage of the actin system to sites of cell-to-substrate adhesion
      in fibroblasts and neuronal growth cones. Gene replacement eliminated the talin
      homologue in Dictyostelium and led to defects in phagocytosis and cell-to
      substrate interaction of moving cells, two processes dependent on a continuous
      cross talk between the cell surface and underlying cytoskeleton. The uptake rate
      of yeast particles was reduced, and only bacteria devoid of the carbohydrate
      moiety of cell surface lipopolysaccharides were adhesive enough to be recruited
      by talin-null cells in suspension and phagocytosed. Cell-to-cell adhesion of
      undeveloped cells was strongly impaired in the absence of talin, in contrast with
      the cohesion of aggregating cells mediated by the phospholipid-anchored contact
      site A glycoprotein, which proved to be less talin dependent. The mutant cells
      were still capable of moving and responding to a chemoattractant, although they
      attached only loosely to a substrate via small areas of their surface. With their
      high proportion of binucleated cells, the talin-null mutants revealed
      interactions of the mitotic apparatus with the cell cortex that were not obvious
      in mononucleated cells.

PMID- 9230078
TI  - Regulation of actin polymerization in cell-free systems by GTPgammaS and Cdc42.
AB  - We have established a cell-free system to investigate pathways that regulate
      actin polymerization. Addition of GTPgammaS to lysates of polymorphonuclear
      leukocytes (PMNs) or Dictyostelium discoideum amoeba induced formation of
      filamentous actin. The GTPgammaS appeared to act via a small G-protein, since it
      was active in lysates ofD. discoideum mutants missing either the alpha2- or beta
      subunit of the heterotrimeric G-protein required for chemoattractant-induced
      actin polymerization in living cells. Furthermore, recombinant Cdc42, but not Rho
      or Rac, induced polymerization in the cell-free system. The Cdc42-induced
      increase in filamentous actin required GTPgammaS binding and was inhibited by a
      fragment of the enzyme PAK1 that binds Cdc42. In a high speed supernatant,
      GTPgammaS alone was ineffective, but GTPgammaS-loaded Cdc42 induced actin
      polymerization, suggesting that the response was limited by guanine nucleotide
      exchange. Stimulating exchange by chelating magnesium, by adding acidic
      phospholipids, or by adding the exchange factors Cdc24 or Dbl restored the
      ability of GTPgammaS to induce polymerization. The stimulation of actin
      polymerization did not correlate with PIP2 synthesis.

PMID- 9230079
TI  - The human Arp2/3 complex is composed of evolutionarily conserved subunits and is
      localized to cellular regions of dynamic actin filament assembly.
AB  - The Arp2/3 protein complex has been implicated in the control of actin
      polymerization in cells. The human complex consists of seven subunits which
      include the actin related proteins Arp2 and Arp3, and five others referred to as
      p41-Arc, p34-Arc, p21-Arc, p20-Arc, and p16-Arc (p omplex). We have determined
      the predicted amino acid sequence of all seven subunits. Each has homologues in
      diverse eukaryotes, implying that the structure and function of the complex has
      been conserved through evolution. Human Arp2 and Arp3 are very similar to family
      members from other species. p41-Arc is a new member of the Sop2 family of WD
      (tryptophan and aspartate) repeat-containing proteins and may be
      posttranslationally modified, suggesting that it may be involved in regulating
      the activity and/or localization of the complex. p34-Arc, p21-Arc, p20-Arc, and
      p16-Arc define novel protein families. We sought to evaluate the function of the
      Arp2/3 complex in cells by determining its intracellular distribution. Arp3, p34
      Arc, and p21-Arc were localized to the lamellipodia of stationary and locomoting
      fibroblasts, as well to Listeria monocytogenes assembled actin tails. They were
      not detected in cellular bundles of actin filaments. Taken together with the
      ability of the Arp2/3 complex to induce actin polymerization, these observations
      suggest that the complex promotes actin assembly in lamellipodia and may
      participate in lamellipodial protrusion.

PMID- 9230080
TI  - CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo.
AB  - Through association with CDK1, cyclin B accumulation and destruction govern the
      G2/M/G1 transitions in eukaryotic cells. To identify CDK1 inactivation-dependent
      events during late mitosis, we expressed a nondestructible form of cyclin B
      (cyclin BDelta90) by microinjecting its mRNA into prometaphase normal rat kidney
      cells. The injection inhibited chromosome decondensation and nuclear envelope
      formation. Chromosome disjunction occurred normally, but anaphase-like movement
      persisted until the chromosomes reached the cell periphery, whereupon they often
      somersaulted and returned to the cell center. Injection of rhodamine-tubulin
      showed that this movement occurred in the absence of a central anaphase spindle.
      In 82% of cells cytokinesis was inhibited; the remainder split themselves into
      two parts in a process reminiscent of Dictyostelium cytofission. In all cells
      injected, F-actin and myosin II were diffusely localized with no detectable
      organization at the equator. Our results suggest that a primary effect of CDK1
      inactivation is on spindle dynamics that regulate chromosome movement and
      cytokinesis. Prolonged CDK1 activity may prevent cytokinesis through inhibiting
      midzone microtubule formation, the behavior of proteins such as TD60, or through
      the phosphorylation of myosin II regulatory light chain.

PMID- 9230082
TI  - Rapid retrograde tyrosine phosphorylation of trkA and other proteins in rat
      sympathetic neurons in compartmented cultures.
AB  - According to the current theory of retrograde signaling, NGF binds to receptors
      on the axon terminals and is internalized by receptor-mediated endocytosis.
      Vesicles with NGF in their lumina, activating receptors in their membranes,
      travel to the cell bodies and initiate signaling cascades that reach the nucleus.
      This theory predicts that the retrograde appearance of activated signaling
      molecules in the cell bodies should coincide with the retrograde appearance of
      the NGF that initiated the signals. However, we observed that NGF applied locally
      to distal axons of rat sympathetic neurons in compartmented cultures produced
      increased tyrosine phosphorylation of trkA in cell bodies/ proximal axons within
      1 min. Other proximal proteins, including several apparently localized in cell
      bodies, displayed increased tyrosine phosphorylation within 5-15 min. However, no
      detectable 125I-NGF appeared in the cell bodies/proximal axons within 30-60 min
      of its addition to distal axons. Even if a small, undetectable fraction of
      transported 125I-NGF was internalized and loaded onto the retrograde transport
      system immediately after NGF application, at least 3-6 min would be required for
      the NGF that binds to receptors on distal axons just outside the barrier to be
      transported to the proximal axons just inside the barrier. Moreover, it is
      unlikely that the tiny fraction of distal axon trk receptors located near the
      barrier alone could produce a measurable retrograde trk phosphorylation even if
      enough time was allowed for internalization and transport of these receptors.
      Thus, our results provide strong evidence that NGF-induced retrograde signals
      precede the arrival of endocytotic vesicles containing the NGF that induced them.
      We further suggest that at least some components of the retrograde signal are
      carried by a propagation mechanism.

PMID- 9230081
TI  - KLP38B: a mitotic kinesin-related protein that binds PP1.
AB  - We have identified a new member of the kinesin superfamily in Drosophila, KLP38B
      (kinesin-like protein at 38B). KLP38B was isolated through its two-hybrid
      interaction with the catalytic subunit of type 1 serine/threonine phosphoprotein
      phosphatase (PP1). We demonstrate that recombinant KLP38B and PP1 associate in
      vitro. This is the first demonstration of direct binding of a kinesin-related
      protein to a regulatory enzyme. Though most closely related to the Unc-104
      subfamily of kinesin-related proteins, KLP38B is expressed only in proliferating
      cells. KLP38B mutants show cell proliferation defects in many tissues. KLP38B is
      required for normal chromatin condensation as embryos from KLP38B mutant mothers
      have undercondensed chromatin at metaphase and anaphase. This is the first time
      that a kinesin-related protein has been shown to have such a role. Incomplete
      lethality of a strong KLP38B allele suggests partial redundancy with one or more
      additional kinesin-related proteins.

PMID- 9230083
TI  - Ezrin is an effector of hepatocyte growth factor-mediated migration and
      morphogenesis in epithelial cells.
AB  - The dissociation, migration, and remodeling of epithelial monolayers induced by
      hepatocyte growth factor (HGF) entail modifications in cell adhesion and in the
      actin cytoskeleton through unknown mechanisms. Here we report that ezrin, a
      membrane-cytoskeleton linker, is crucial to HGF-mediated morphogenesis in a
      polarized kidney-derived epithelial cell line, LLC-PK1. Ezrin is a substrate for
      the tyrosine kinase HGF receptor both in vitro and in vivo. HGF stimulation
      causes enrichment of ezrin recovered in the detergent-insoluble cytoskeleton
      fraction. Overproduction of wild-type ezrin, by stable transfection in LLC-PK1
      cells, enhances cell migration and tubulogenesis induced by HGF stimulation.
      Overproduction of a truncated variant of ezrin causes mislocalization of
      endogenous ezrin from microvilli into lateral surfaces. This is concomitant with
      altered cell shape, characterized by loss of microvilli and cell flattening.
      Moreover, the truncated variant of ezrin impairs the morphogenic and motogenic
      response to HGF, thus suggesting a dominant-negative mechanism of action. Site
      directed mutagenesis of ezrin codons Y145 and Y353 to phenylalanine does not
      affect the localization of ezrin at microvilli, but perturbs the motogenic and
      morphogenic responses to HGF. These results provide evidence that ezrin displays
      activities that can control cell shape and signaling.

PMID- 9230084
TI  - Cellular localization, expression, and structure of the nuclear dot protein 52.
AB  - Nuclear dots containing PML and Sp100 proteins (NDs) play a role in the
      development of acute promyelocytic leukemia, are modified after infection with
      various viruses, and are autoimmunogenic in patients with primary biliary
      cirrhosis (PBC). PML and Sp100 gene expression is strongly enhanced by
      interferons (IFN). Based on immunostaining with a monoclonal antibody (mAb C8A2),
      a third protein, nuclear dot protein 52 (NDP52), was recently localized in NDs.
      Here we analyzed the cellular localization, expression, and structure of NDP52 in
      more detail. Our NDP52-specific sera revealed mainly cytoplasmic staining but no
      ND pattern, neither in untreated nor in IFN-treated cells. Cells transfected with
      NDP52 expression vectors showed exclusively cytoplasmic staining. In subcellular
      fractionation experiments, NDP52 was found in cytoplasmic and nuclear fractions.
      Unlike as described for Sp100 and PML, NDP52 mRNA and protein levels were only
      marginally enhanced by IFN gamma and not enhanced at all by IFN beta. NDP52
      homodimerization but no heterodimerization with Sp100 or PML could be
      demonstrated. None of the 93 PBC sera tested contained autoantibodies against
      NDP52. Finally, mAb C8A2 reacted not only with NDP52 but also with a conformation
      dependent epitope on the Sp100 protein. These data imply that NDP52 forms
      homodimers but no heterodimers with Sp100 and PML, lacks autoantigenicity in PBC,
      localizes mainly in the cytoplasm, and is associated with the nucleus, but not
      with NDs. Finally, unlike Sp100 and PML, NDP52 expression is neither markedly
      enhanced nor localization detectably altered by type I and II IFNs.

PMID- 9230087
TI  - Renal transporters for organic anions and organic cations. Structural
      requirements for substrates.

PMID- 9230086
TI  - Interactions between germ cells and extracellular matrix glycoproteins during
      migration and gonad assembly in the mouse embryo.
AB  - Cells are known to bind to individual extracellular matrix glycoproteins in a
      complex and poorly understood way. Overall strength of adhesion is thought to be
      mediated by a combinatorial mechanism, involving adhesion of a cell to a variety
      of binding sites on the target glycoproteins. During migration in embryos, cells
      must alter their overall adhesiveness to the substrate to allow locomotion. The
      mechanism by which this is accomplished is not well understood. During early
      development, the cells destined to form the gametes, the primordial germ cells
      (PGCs), migrate from the developing hind gut to the site where the gonad will
      form. We have used whole-mount immunocytochemistry to study the changing
      distribution of three extracellular matrix glycoproteins, collagen IV,
      fibronectin, and laminin, during PGC migration and correlated this with
      quantitative assays of adhesiveness of PGCs to each of these. We show that PGCs
      change their strength of adhesion to each glycoprotein differentially during
      these stages. Furthermore, we show that PGCs interact with a discrete tract of
      laminin at the end of migration. Closer analysis of the adhesion of PGCs to
      laminin revealed that PGCs adhere particularly strongly to the E3 domain of
      laminin, and blocking experiments in vitro suggest that they adhere to this
      domain using a cell surface proteoglycan.

PMID- 9230088
TI  - Ion, fluid and charge transport across Necturus intestinal epithelium in response
      to alanine.
AB  - Fluxes of Na, Cl and volume were followed across Necturus small intestine under
      zero voltage clamp. 20 mM L-alanine doubles the net Na and fluid transfer.
      Although there is a ouabain-sensitive Na pump present in Necturus a major
      fraction of the net Na flux can be measured for an hour after application of 10(
      3) M ouabain. Collected fluid transferred by the epithelium is quasi-isotonic
      over a range of luminal osmolarities from 100 to 250 milliosmolar in alanine
      saline. The net Na fluxes account for the Na found in this transported fluid.
      Fluid transfer also shows a large ouabain-insensitive fraction after the addition
      of alanine. Compartmental analysis of 22Na-loaded epithelium was used to separate
      cellular and paracellular fluxes. The estimated Na concentration in the cell
      derived from its Na content is 9-10 mM, in agreement with that determined with
      microelectrodes. The Na efflux from cell to serosa is stimulated by alanine, but
      this increase accounts for only a quarter of the simultaneous rises in Na, fluid
      and current flow across the epithelium. The increase of Na efflux from the cell
      induced by alanine is apparently insensitive to ouabain although the cell Na
      content rises to circa 20 mM but no higher even after 20 hr. From the initial
      rate of rise of Na in the cell on treatment with ouabain the activity of the Na
      pump can be estimated to be approximately 92 pM/cm2 . sec, a value much smaller
      than the transepithelial net flux. The results are not consistent with the
      standard model in which Na-alanine influx stimulates the Na pump and enhances
      fluid transport by osmotic coupling in the lateral interspace system. A scheme is
      proposed based upon that for absorption in Necturus gallbladder by which alanine
      stimulates an active paracellular fluid transfer driven by motile elements of the
      junction.

PMID- 9230089
TI  - Fluid recirculation in Necturus intestine and the effect of alanine.
AB  - Fluid absorption by Necturus small intestine has been studied using radiolabeled
      dextrans as molecular probes of the paracellular pathway under voltage-clamped
      conditions. Fluxes of H3-dextrans of MW up to 20K were followed in both
      directions between mucosal (M) and serosal (S) baths by fractionating those that
      passed the epithelium as a function of molecular radius. Consideration of the
      unstirred layers in the baths and the surface geometry rules out any contribution
      made by solute polarization. The geometry of the paracellular system was measured
      by light microscopy, TEM and SEM, and values were used in conjunction with a
      program that calculates convective-diffusive coupling in the tight junctions,
      intercellular spaces and subepithelium in series. The results indicate that the
      net fluxes are due to the convection of fluid through two opposing paracellular
      fluid circuits with different size selectivity, resulting in net absorption at
      small radii. Alanine at 20 mM stimulates fluid and salt uptake by a factor of 2.
      Its effect on the two convective components is to increase the M to S flux and
      decrease the S to M. The selectivities are not significantly different from those
      before alanine treatment. The volume absorption predicted from the net probe
      fluxes is very close to that measured gravimetrically across the epithelium.

PMID- 9230085
TI  - Mitochondrial proliferation and paradoxical membrane depolarization during
      terminal differentiation and apoptosis in a human colon carcinoma cell line.
AB  - Herbimycin A, a tyrosine kinase inhibitor, induces cellular differentiation and
      delayed apoptosis in Colo-205 cells, a poorly differentiated human colon
      carcinoma cell line. Cell cycle analysis in conjunction with end labeling of DNA
      fragments revealed that G2 arrest preceded apoptotic cell death. Ultrastructural
      examination of herbimycin-treated cells demonstrated morphologic features of
      epithelial differentiation, including formation of a microvillar apical membrane
      and lateral desmosome adhesions. A marked accumulation of mitochondria was also
      observed. Fluorometric analysis using the mitochondrial probes nonyl-acridine
      orange and JC-1 confirmed a progressive increase in mitochondrial mass. However
      these cells also demonstrated a progressive decline in unit mitochondrial
      transmembrane potential (DeltaPsim) as determined by the DeltaPsim-sensitive
      fluorescent probes rhodamine 123 and JC-1 analyzed for red fluorescence. In
      concert with these mitochondrial changes, Colo-205 cells treated with herbimycin
      A produced increased levels of reactive oxygen species as evidenced by oxidation
      of both dichlorodihydrofluorescein diacetate and dihydroethidium. Cell-free
      assays for apoptosis using rat-liver nuclei and extracts of Colo-205 cells at 24
      h showed that apoptotic activity of Colo-205 lysates requires the early action of
      mitochondria. Morphological and functional mitochondrial changes were observed at
      early time points, preceding cleavage of poly (ADP-ribose) polymerase. These
      results suggest that apoptosis in differentiated Colo-205 cells involves
      unrestrained mitochondrial proliferation and progressive membrane dysfunction, a
      novel mechanism in apoptosis.

PMID- 9230091
TI  - Balance of electrostatic and hydrophobic interactions in the lysis of model
      membranes by E. coli alpha-haemolysin.
AB  - The relative weight of electrostatic interactions and hydrophobic forces in the
      process of membrane disruption caused by E. coli alpha-haemolysin (HlyA) has been
      studied with a purified protein preparation and a model system consisting of
      large unilamellar vesicles loaded with water-soluble fluorescent probes. Vesicles
      were prepared in buffers of different ionic strengths, or pHs, and the net
      surface charge of the bilayers was also modified by addition of negatively (e.g.,
      phosphatidylinositol) or positively (e.g., stearylamine) charged lipids. The
      results can be interpreted in terms of a multiple equilibrium in which alpha
      haemolysin may exist: aggregated HlyA <==> monomeric HlyA <==> membrane-bound
      HlyA. In these equilibria both electrostatic and hydrophobic forces are
      significant. Electrostatic forces become substantial under certain circumstances,
      e.g., membrane binding when bilayer and protein have opposite electric charges.
      Protein adsorption to the bilayer is more sensitive to electrostatic forces than
      membrane disruption itself. In the latter case, the irreversible nature of
      protein insertion may overcome electrostatic repulsions. Also of interest is the
      complex effect of pH on the degree of aggregation of an amphipathic toxin like
      alpha-haemolysin, since pH changes are not only influencing the net protein
      charge but may also be inducing protein conformational transitions shown by
      changes in the protein intrinsic fluorescence and in its susceptibility to
      protease digestion, that appear to regulate the presence of hydrophobic patches
      at the surface of the molecule, thus modifying the ability of the toxin to either
      aggregate or become inserted in membranes.

PMID- 9230090
TI  - Regulatory volume decrease by SV40-transformed rabbit corneal epithelial cells
      requires ryanodine-sensitive Ca2+-induced Ca2+ release.
AB  - The relationship between relative cell volume and time-dependent changes in
      intracellular Ca2+ concentration ([Ca2+]i) during exposure to hypotonicity was
      characterized in SV-40 transformed rabbit corneal epithelial cells (tRCE) (i).
      Light scattering measurements revealed rapid initial swelling with subsequent 97%
      recovery of relative cell volume (characteristic time (tauvr) was 5.9 min); (ii).
      Fura2-fluorescence single-cell imaging showed that [Ca2+]i initially rose by 216%
      in 30 sec with subsequent return to near baseline level after another 100 sec.
      Both relative cell volume recovery and [Ca2+]i transients were inhibited by
      either: (a) Ca2+-free medium; (b) 5 mM Ni2+ (inhibitor of plasmalemma Ca2+
      influx); (c) 10 microM cyclopiazonic acid, CPA (which causes depletion of
      intracellular Ca2+ content); or (d) 100 microM ryanodine (inhibitor of Ca2+
      release from intracellular stores). To determine the temporal relationship
      between an increased plasmalemma Ca2+ influx and the emptying of intracellular
      Ca2+ stores during the [Ca2+]i transients, Mn2+ quenching of fura2-fluorescence
      was quantified. In the presence of CPA, hypotonic challenge increased plasmalemma
      Mn2+ permeability 6-fold. However, Mn2+ permeability remained unchanged during
      exposure to either: 1.100 microM ryanodine; 2.10 microM CPA and 100 microM
      ryanodine. This report for the first time documents the time dependence of the
      components of the [Ca2+]i transient required for a regulatory volume decrease
      (RVD). The results show that ryanodine sensitive Ca2+ release from an
      intracellular store leads to a subsequent increase in plasmalemma Ca2+ influx,
      and that both are required for cells to undergo RVD.

PMID- 9230093
TI  - Large-conductance cation channels in the envelope of nuclei from rat cerebral
      cortex.
AB  - Eucaryotic nuclei are surrounded by a double-membrane system enclosing a central
      cisterna which is continuous with the endoplasmic reticulum and serves as a
      calcium store for intracellular signaling. The envelope regulates protein and
      nucleic acid traffic between the nucleus and the cytoplasm via nuclear pores.
      These protein tunnels cross through both nuclear membranes and are permeable for
      large molecules. Surprisingly, patch clamp recordings from isolated nuclei of
      different cell species have revealed a high resistance of the envelope, enabling
      tight seals and the resolution of single ion channel activity. Here we present
      for the first time single-channel recordings from nuclei prepared from neuronal
      tissue. Nuclei isolated from rat cerebral cortex displayed spontaneous long
      lasting large conductances in the nucleus-attached mode as well as in excised
      patches. The open times are in the range of seconds and channel activity
      increases with depolarization. The single-channel conductance in symmetrical K+
      is 166 pS. The channels are selective for cations with PK/PNa = 2. They are
      neither permeable to, nor gated by Ca2+. Thus, neuronal tissue nuclei contain a
      large conductance ion channel selective for monovalent cations which may
      contribute to ionic homeostasis in the complex compartments surrounding these
      organelles.

PMID- 9230092
TI  - Effects of thiol-modifying agents on a K(Ca2+) channel of intermediate
      conductance in bovine aortic endothelial cells.
AB  - Ca2+-activated K+ channels (K(Ca2+)) constitute key regulators of the endothelial
      cell electrophysiological response to InsP3-mobilizing agonists. Inside-out and
      outside-out patch clamp experiments were thus undertaken to determine if the
      gating properties of a voltage-insensitive K(Ca2+) channel of intermediate
      conductance present in bovine aortic endothelial (BAE) cells could be modified by
      specific sulfhydryl (SH) oxidative and/or reducing reagents. The results obtained
      first indicate that cytosolic application of hydrophilic oxidative reagents such
      as 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) (0.2 to 5 mM) or [(O
      carboxyphenyl)thio]ethyl mercury sodium salt (thimerosal) (0.5 to 5 mM) reduces
      gradually the K(Ca2+) channel activity with no modification of the channel
      unitary conductance. The inhibitory action of DTNB (1 to 5 mM) or thimerosal (1
      to 5 mM) was not reserved following withdrawal of the oxidative agents, but
      channel activity could partly be restored by the addition of the SH group
      reducing agents dithiothreitol (DTT) (5 mM) or reduced glutathione (GSH) (5 mM)
      in 53% and 50% of the inside-out experiments performed with DTNB and thimerosal
      respectively. Similar results were obtained using H2O2 at concentrations ranging
      from 500 microM to 10 mm as oxidative reagent. In contrast, the lipid soluble
      oxidative agent 4,4'-dithiodipyridine (4-PDS) (1 mM) appeared in inside-out
      experiments less potent than DTNB and thimerosal at inhibiting the K(Ca2+)
      channel activity, suggesting that the critical SH groups involved in channel
      gating are localized at the inner face of the cell membrane. This conclusion was
      further substantiated by a series of outside-out patch clamp experiments which
      showed that DTNB (5 mM) and thimerosal (5 mM) were unable to inhibit the K(Ca2+)
      channel activity when applied to the external surface of the excised membrane.
      Finally, no significant changes of the gating properties of the K(Ca2+) channel
      were observed in inside-out experiments where the SH group reducing agents DTT
      and GSH were applied immediately following membrane excision. However, the
      application of either GSH or DTT was found to partly restore channel activity in
      experiments where the K(Ca2+) channels showed significant rundown.

PMID- 9230095
TI  - Catabolic Gene Probe Analysis of an Aquifer Microbial Community Degrading
      Creosote-Related Polycyclic Aromatic and Heterocyclic Compounds

PMID- 9230094
TI  - A large-conductance chloride channel in pigmented ciliary epithelial cells
      activated by GTPgammaS.
AB  - A large-conductance (or maxi-) chloride channel was identified in bovine
      pigmented ciliary epithelial (PCE) cells using inside-out excised patch clamp
      recording. The channel had a mean conductance of 293 pS when excised patches were
      bathed in symmetrical 130 mm NaCl although the conductance decreased to 209 pS
      when the solution bathing the cytoplasmic face of the patch contained only 33 mm
      NaCl. The channel was highly selective for chloride, with a PCl/PNa = 24. A
      flickery, reversible block was produced by the diuretic stilbene 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid (SITS), while 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) produced a permanent block.
      The channel was rarely active in cell-attached patches and usually required
      several minutes of polarization before activity could be detected in excised
      patches, a process known as metagenesis. Once activated, the channel was voltage
      dependent and was mainly open within the voltage range -30 to +30 mV closing when
      the membrane was polarized to larger values. GTPgammaS (100 microM) activated the
      channel with a latency of 170 sec when applied to the cytoplasmic face of
      patches. This activation was not reversible upon return to control solution
      within the duration of the experiment. We assess the available evidence and
      suggest a role for this channel in volume regulation.

PMID- 9230097
TI  - Detection and Quantification with 16S rRNA Probes of Planktonic Methylotrophic
      Bacteria in a Floodplain Lake

PMID- 9230096
TI  - Distribution of the tfdA Gene in Soil Bacteria That Do Not Degrade 2,4
      Dichlorophenoxyacetic Acid (2,4-D)

PMID- 9230098
TI  - Bacterial Community Structure in Relation to the Carbon Environments in Lettuce
      and Tomato Rhizospheres and in Bulk Soil

PMID- 9230099
TI  - Antagonistic Activities of Epiphytic Bacteria from Soybean Leaves against
      Pseudomonas syringae pv. glycinea in vitro and in planta

PMID- 9230100
TI  - Microbial Diversity and Community Structure of Postdisturbance Forest Soils as
      Determined by Sole-Carbon-Source Utilization Patterns

PMID- 9230101
TI  - Microbial Response of a Freshwater Benthic Community to a Simulated Diatom
      Sedimentation Event: Interactive Effects of Benthic Fauna

PMID- 9230102
TI  - Coupling Between Rates of Bacterial Production and the Abundance of Metabolically
      Active Bacteria in Lakes, Enumerated Using CTC Reduction and Flow Cytometry

PMID- 9230103
TI  - Influence of Protozoa and Nutrient Availability on Nitrification Rates in
      Subsurface Sediments

PMID- 9230105
TI  - Co-operation of phosphatidylinositol transfer protein with phosphoinositide 3
      kinase gamma in the formylmethionyl-leucylphenylalanine-dependent production of
      phosphatidylinositol 3,4,5-trisphosphate in human neutrophils.
AB  - Phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol 3,4,5
      trisphosphate (PIP3) play an essential role in the regulation of neutrophil
      functions by the chemoattractant formylmethionyl-leucylphenylalanine (FMLP). Here
      we show that permeabilization of human neutrophils leads to loss of cytosolic
      components, including PI3Kgamma, and causes the loss of FMLP-dependent production
      of PIP3. FMLP-sensitive synthesis of PIP3 could be restored by reconstitution of
      permeabilized neutrophils with recombinant PI3Kgamma. Admixture of recombinant
      phosphatidylinositol transfer protein (PITP) to the reconstitution cocktail
      produced a further increase of PIP3 synthesis, whereas pertussis toxin suppressed
      the FMLP-dependent production of PIP3. We conclude that FMLP-sensitive PIP3
      formation in human neutrophils involves the FMLP receptor, heterotrimeric G
      proteins of the Gi type, PI3Kgamma and PITP.

PMID- 9230104
TI  - Interactions of polyamines with ion channels.
AB  - Endogenous polyamines, in particular spermine, have been found to cause block and
      modulation of a number of types of ion channel. Intracellular spermine is
      responsible for intrinsic gating and rectification of strong inward rectifier K+
      channels by directly plugging the ion channel pore. These K+ channels control the
      resting membrane potential in both excitable and non-excitable cells, and control
      the excitability threshold in neurons and muscle cells. Intracellular spermine
      causes inward rectification at some subtypes of Ca2+-permeable glutamate
      receptors in the central nervous system, again by plugging the receptor channel
      pore, and spermine can even permeate the ion channel of these receptors.
      Extracellular spermine has multiple effects at the N-methyl-d-aspartate (NMDA)
      subtype of glutamate receptor, including stimulation that increases the size of
      NMDA receptor currents, and voltage-dependent block. A number of polyamine
      conjugated arthropod toxins and synthetic polyamine analogues are potent
      antagonists of glutamate receptors, and represent new tools with which to study
      these receptors. Interactions of polyamines with other types of cation channels
      have been reported. This area of research represents a new biology and a new
      pharmacology of polyamines.

PMID- 9230106
TI  - Platelet-derived growth factor activation of mitogen-activated protein kinase
      depends on the sequential activation of phosphatidylcholine-specific
      phospholipase C, protein kinase C-zeta and Raf-1.
AB  - The mechanism of Raf-1 activation by platelet-derived growth factor (PDGF) is
      poorly defined. We previously reported that, in Rat-1 fibroblasts, PDGF activates
      a phosphatidylcholine-specific phospholipase C (PC-PLC) and that the product,
      diacylglycerol, somehow activates protein kinase C-zeta (PKC-zeta). Both PC-PLC
      and PKC-zeta activities were required for PDGF activation of mitogen-activated
      protein kinase (MAPK). Now we report that MAPK activation by exogenous PC-PLC
      depends on Raf-1 activation. PKC-zeta co-immunoprecipitates with, phoshorylates
      and activates Raf-1, suggesting that in the PDGF- and PC-PLC-activated MAPK
      pathway, PKC-zeta operates in a signalling complex as a direct activator of Raf
      1.

PMID- 9230107
TI  - The peptide LSARLAF causes platelet secretion and aggregation by directly
      activating the integrin alphaIIbbeta3.
AB  - A novel peptide (designed to bind to alphaIIbbeta3) caused platelet aggregation
      and aggregation-independent secretion of the contents of alpha-granules in an
      alphaIIbbeta3-dependent fashion. The agonist peptide induced secretion in the
      presence of prostaglandin E1. In cell-free assays, alphaIIbbeta3 bound
      specifically to immobilized agonist peptide and the peptide enhanced the binding
      of fibrinogen to immobilized alphaIIbbeta3. The agonist peptide apparently
      activates alphaIIbbeta3 by directly inducing a conformational change in the
      receptor. This change activates the platelets and causes secretion in a manner
      independent of fibrinogen binding.

PMID- 9230109
TI  - The study of cell-death proteins in the outer mitochondrial membrane by chemical
      cross-linking.
AB  - Chemical cross-linking was used to study the interactions of the anti-cell-death
      protein Bcl2 with other proteins in the outer mitochondrial membrane. Cross
      linking of mitochondrial surface proteins produced a large Bcl2-containing
      complex (>200 kDa), and a Bcl2-derived peptide was shown to cross-link
      specifically with a mitochondrial protein identified by immunoblotting as Raf-1
      kinase.

PMID- 9230110
TI  - New de-ubiquitinating enzyme, ubiquitin C-terminal hydrolase 8, in chick skeletal
      muscle.
AB  - We have previously shown that chick muscle extracts contained at least 10
      different ubiquitin C-terminal hydrolases (UCHs). Here we report the purification
      and characterization of one of the UCHs, called UCH-8, with 125I-labelled
      ubiquitin-alpha-NH-MHISPPEPESEEEEEHYC as a substrate. The purified UCH-8 behaved
      as a 240 kDa protein on a Superdex-200 column under non-denaturing conditions but
      as a 130 kDa polypeptide on analysis by PAGE under denaturing conditions,
      suggesting that the enzyme consists of two identical subunits. Thus this enzyme
      seems to be distinct in its dimeric nature from other purified UCHs that consist
      of a single polypeptide, except that UCH-6 is also a homodimer of 27 kDa
      subunits. UCH-8 was maximally active between pH 7.5 and 8, but showed little or
      no activity below pH 7 and above pH 9. Like other UCHs it was sensitive to
      inhibition by thiol-blocking agents such as N-ethylmaleimide, and by ubiquitin
      aldehyde. The purified UCH-8 hydrolysed not only ubiquitin-alpha-NH-protein
      extensions, including ubiquitin-alpha-NH-carboxy extension protein of 80 amino
      acid residues and ubiquitin-alpha-NH-dihydrofolate reductase, but also branched
      poly-ubiquitin that are ligated to proteins through epsilon-NH-isopeptide bonds.
      However, it showed little or no activity against poly-His-tagged di-ubiquitin,
      suggesting that UCH-8 is not involved in the generation of free ubiquitin from
      the linear poly-ubiquitin precursors. These results suggest that UCH-8 might have
      an important role in the production of free ubiquitin and ribosomal proteins from
      their conjugates as well as in the recycling of ubiquitin molecules after the
      degradation of poly-ubiquitinated protein conjugates by the 26 S proteasome.

PMID- 9230108
TI  - Bcl-xL overexpression attenuates glutathione depletion in FL5.12 cells following
      interleukin-3 withdrawal.
AB  - Bcl-xL and bax are bcl-2-related genes whose protein products either inhibit or
      promote apoptosis. Oxidative damage, including the loss of glutathione, has been
      implicated in the induction of apoptosis. The ability of the Bcl proteins to
      affect GSH was assessed in control, bax- and bcl-xL-transfected FL5.12 cells [an
      interleukin (IL)-3-dependent murine prolymphocytic cell line]. Overall levels of
      GSH were approximately the same in control and bcl-xL transfectants during the 6
      h incubation period, although levels increased in bcl-xL transfectants 24 h after
      replating. GSH in cells overexpressing bax was reduced by approximately 36%.
      There were no consistent differences between these cell lines in the activities
      of superoxide dismutase, catalase, glutathione peroxidase or glutathione
      reductase. Following IL-3 withdrawal, a condition known to cause apoptosis in
      these cells, a rapid loss of intracellular GSH occurred in control and bax
      transfectants, which preceded the onset of apoptosis. GSH depletion could not be
      attributed to intracellular oxidation but rather seemed to occur due to a
      translocation out of the cell. Cells overexpressing bcl-xL did not lose
      significant amounts of GSH upon withdrawal of IL-3, and no apoptosis was evident.
      These results suggest a possible role for GSH in the mechanism by which bcl-xL
      prevents cell death.

PMID- 9230111
TI  - Overexpression of arginine decarboxylase in transgenic plants.
AB  - The activity of arginine decarboxylase (ADC), a key enzyme in plant polyamine
      biosynthesis, was manipulated in two generations of transgenic tobacco plants.
      Second-generation transgenic plants overexpressing an oat ADC cDNA contained high
      levels of oat ADC transcript relative to tobacco ADC, possessed elevated ADC
      enzyme activity and accumulated 10-20-fold more agmatine, the direct product of
      ADC. In the presence of high levels of the precursor agmatine, no increase in the
      levels of the polyamines putrescine, spermidine and spermine was detected in the
      transgenic plants. Similarly, the activities of ornithine decarboxylase and S
      adenosylmethionine decarboxylase were unchanged. No diversion of polyamine
      metabolism into the hydroxycinnamic acid-polyamine conjugate pool or into the
      tobacco alkaloid nicotine was detected. Activity of the catabolic enzyme diamine
      oxidase was the same in transgenic and control plants. The elevated ADC activity
      and agmatine production were subjected to a metabolic/physical block preventing
      increased, i.e. deregulated, polyamine accumulation. Overaccumulation of agmatine
      in the transgenic plants did not affect morphological development.

PMID- 9230112
TI  - The cluster of basic amino acids in vitronectin contributes to its binding of
      plasminogen activator inhibitor-1: evidence from thrombin-, elastase- and plasmin
      cleaved vitronectins and anti-peptide antibodies.
AB  - Derivatives of vitronectin obtained by specific cleavage at its cluster of basic
      amino acids with thrombin, elastase and plasmin are shown to have a decreased
      ability to bind plasminogen activator inhibitor-1 (PAI-1). The identification and
      localization of the segment involved in the binding of PAI-1 (Lys348-Arg379) were
      carried out by purification of these cleaved vitronectins and their subsequent
      structural characterization (sequence analysis, phosphorylation of Ser378 with
      cAMP-dependent protein kinase and immunostaining with peptide-specific
      antibodies), then measurement of the vitronectin-PAI-1 interaction by (a) a two
      phase system (ELISA); (b) co-precipitation of the vitronectin-PAI-1 complex out
      of solution, and (c) analysis of the stereospecific interaction between the
      active conformation of PAI-1 and a peptide derived from the above-mentioned
      cluster; this interaction occurs when the peptide is composed of all-l-amino
      acids but not when it is composed of all-d-amino acids. Our results explain why
      workers who have used immobilized vitronectin to study this interaction could not
      have observed the involvement of the cluster of basic amino acids in PAI-1
      binding, since the immobilization of vitronectin is shown to render this cluster
      inaccessible for interaction. We propose that vitronectin binds active PAI-1 by
      interaction via amino acid residues that originate from distal locations in the N
      and C-termini of vitronectin.

PMID- 9230113
TI  - Localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase to
      the trans-Golgi network.
AB  - In order to determine the intracellular location of heparan N-deacetylase/N
      sulphotransferase, cDNAs encoding human heparan glucosaminyl N-deacetylase/N
      sulphotransferase were cloned from human umbilical vein endothelial cells. The
      deduced amino acid sequence was identical to that of the human heparan N
      sulphotransferase cloned previously [Dixon, Loftus, Gladwin, Scambler, Wasmuth
      and Dixon (1995) Genomics 26, 239-244]. RNA blot analysis indicated that two
      heparan N-sulphotransferase transcripts of approx. 8.5 and 4 kb were produced in
      all tissues. Expression was most abundant in heart, liver and pancreas. A cDNA
      encoding a Flag-tagged human heparan N-sulphotransferase (where Flag is an
      epitope with the sequence DYKDDDDK) was transfected into mouse LTA cells.
      Immunofluorescence detection using anti-Flag monoclonal antibodies demonstrated
      that the enzyme was localized to the trans-Golgi network. A truncated Flag-tagged
      heparan N-sulphotransferase was also retained in the Golgi, indicating that, as
      for many other Golgi enzymes, the N-terminal region of heparan N
      sulphotransferase is sufficient for retention in the Golgi apparatus.

PMID- 9230114
TI  - Co-amplification explains linkage disequilibrium of two mosquito esterase genes
      in insecticide-resistant Culex quinquefasciatus.
AB  - The mosquito Culex quinquefasciatus (Say) is a vector of human disease and a
      world-wide biting nuisance. Organophosphorus insecticides (OPs) have been widely
      used to control C. quinquefasciatus populations and this has led to the emergence
      of OP-resistance. Predominantly, resistance is caused by increased production of
      two non-specific carboxylesterases, Estalpha2(1) and Estbeta2(1). Increased
      abundance of these esterases is associated with the amplification of their
      respective genes. The estalpha21 and estbeta21 genes were cloned and sequenced
      from OP-resistant Sri Lankan C. quinquefasciatus; the two adjacent genes are in a
      head to head configuration, within a single amplification unit (amplicon). The
      homology between the two genes suggests that they arose from an ancient
      duplication event. The two genes have different numbers of exons (estalpha21 has
      seven and estbeta21 has four); however, the intron/exon boundaries in estbeta21
      are all conserved in estalpha21. The two genes are co-amplified in three other
      mosquito strains with the elevated Estalpha2(1)/Estbeta2(1) phenotype. Their
      complete linkage disequilibrium is explained by the location of the two genes
      involved in resistance within a single amplicon. In insecticide-susceptible C.
      quinquefasciatus, the non-amplified estalpha and estbeta gene loci are also found
      in a similar head to head configuration, but the size of the intergenic non
      coding region is approx. 1 kb less than in the amplicon. The smaller intergenic
      spacer is also found in a strain with amplified estbeta11, which suggests that
      extensive laboratory selection for this amplified esterase has not eliminated the
      non-amplified genes. The intergenic spacer regions have been subcloned and
      sequenced. They contain numerous possible TATA boxes, promoters and a number of
      possible regulatory elements with high homology to the consensus sequence of the
      Barbie box. These latter putative regulatory elements are more numerous in the
      larger intergenic spacer, which differs from the non-amplified spacer by two
      large (>>420 bp) and one small (5 bp) insertions.

PMID- 9230115
TI  - Evidence that multifunctional protein 2, and not multifunctional protein 1, is
      involved in the peroxisomal beta-oxidation of pristanic acid.
AB  - The second (enoyl-CoA hydratase) and third (3-hydroxyacyl-CoA dehydrogenase)
      steps of peroxisomal beta-oxidation are catalysed by two separate multifunctional
      proteins (MFPs), MFP-1 being involved in the degradation of straight-chain fatty
      acids and MFP-2 in the beta-oxidation of the side chain of cholesterol (bile acid
      synthesis). In the present study we determined which of the two MFPs is involved
      in the peroxisomal degradation of pristanic acid by using the synthetic analogue
      2-methylpalmitic acid. The four stereoisomers of 3-hydroxy-2-methylpalmitoyl-CoA
      were separated by gas chromatography after hydrolysis, methylation and
      derivatization of the hydroxy group with (S)-2-phenylpropionic acid, and the
      stereoisomers were designated I-IV according to their order of elution from the
      column. Purified MFP-1 dehydrated stereoisomer IV but dehydrogenated stereoisomer
      III, so by itself MFP-1 is not capable of converting a branched enoyl-CoA into a
      3-ketoacyl-CoA. In contrast, MFP-2 dehydrated and dehydrogenated the same
      stereoisomer (II), so it is highly probable that MFP-2 is involved in the
      peroxisomal degradation of branched fatty acids and that stereoisomer II is the
      physiological intermediate in branched fatty acid oxidation. By analogy with the
      results obtained with the four stereoisomers of the bile acid intermediate
      varanoyl-CoA, stereoisomer II can be assigned the 3R-hydroxy, 2R-methyl
      configuration.

PMID- 9230116
TI  - Adhesion of fibroblasts to fibronectin stimulates both serine and tyrosine
      phosphorylation of paxillin.
AB  - Tyrosine phosphorylation of paxillin by the focal adhesion kinase (FAK) has been
      implicated as a signal transduction mechanism associated with cell adhesion and
      cytoskeletal reorganization. The potential role of serine phosphorylation of
      paxillin in these events has not been well characterized. In this study we have
      examined the phosphorylation profile of paxillin both in vitro and in vivo. By
      using glutathione S-transferase-paxillin fusion proteins in precipitation-kinase
      assays in vitro we observed that a fusion protein spanning amino acid residues 54
      313 of paxillin, and containing a FAK-binding site, precipitated substantial
      serine kinase activity as well as FAK activity from a smooth-muscle lysate.
      Together these kinases phosphorylated paxillin on tyrosine residue 118, a site
      that has been identified previously as a target for FAK phosphorylation, and on
      serine residues 188 and/or 190. The binding site for the serine kinase, the
      identity of which is currently unknown, was further mapped to residues 168-191 of
      paxillin. To assess the physiological relevance of these sites phosphorylated in
      vitro, the profile of paxillin phosphorylation in vivo stimulated by seeding
      fibroblasts on fibronectin was characterized. As expected, plating cells on
      fibronectin enhanced the tyrosine phosphorylation of paxillin. However, 96% of
      the phosphorylation of paxillin occurred on serine residues. Comparison by two
      dimensional phosphopeptide analyses indicated that the major sites of tyrosine
      and serine phosphorylation detected in the assays in vitro co-migrate with
      phosphopeptides derived from paxillin phosphorylated in vivo in response to
      plating cells on fibronectin. These findings support a role for both tyrosine and
      serine kinases in the signal transduction pathway linking integrin activation to
      paxillin phosphorylation.

PMID- 9230117
TI  - Ca2+ and protein kinase C-dependent mechanisms involved in gastrin-induced
      Shc/Grb2 complex formation and P44-mitogen-activated protein kinase activation.
AB  - The proliferative effects of gastrin on normal and neoplastic gastro-intestinal
      tissues have been shown to be mediated by the gastrin/CCKB (G/CCKB) G-protein
      coupled receptors. We have recently reported that gastrin stimulates the tyrosine
      phosphorylation of Shc proteins and their subsequent association with the
      Grb2/Sos complex, leading to mitogen-activated protein kinase (MAPK) activation,
      a pathway known to play an important role in cell proliferation. We undertook the
      present study to characterize the signalling pathways used by this receptor to
      mediate the activation of the Shc/Grb2 complex. Since G/CCKB receptor occupancy
      leads to the activation of the phospholipase C (PLC)/protein kinase C (PKC)
      pathway, we examined whether PKC stimulation and Ca2+ mobilization contribute to
      the phosphorylation of Shc proteins and their association with Grb2 in response
      to gastrin. Our results indicate that Shc proteins are tyrosine phosphorylated
      and associate with Grb2 in response to phorbol esters, suggesting that activation
      of PKC is a potential signalling pathway leading to activation of the Shc/Grb2
      complex. Inhibition of PKC by GF109203X completely blocked the effect of PMA on
      Shc tyrosine phosphorylation and its subsequent association with Grb2, but had a
      partial inhibitory effect on the response to gastrin. Depletion of the
      intracellular Ca2+ pools by treatment with thapsigargin blocked the increase in
      intracellular free calcium concentration induced by gastrin and diminished the
      ability of the peptide to stimulate Shc phosphorylation and recruitment of Grb2.
      In addition, removal of extracellular Ca2+ partially inhibited the effect of
      gastrin on Shc phosphorylation as well as its association with Grb2, indicating
      that the effects of gastrin are also mediated by Ca2+-dependent mechanisms.
      Furthermore, we show that blockage of the two major early signals generated by
      activation of PLC, which induced the activation of the Shc/Grb2 complex, also
      blocked gastrin-induced MAPK activation.

PMID- 9230118
TI  - Asymmetry adjacent to the collagen-like domain in rat liver mannose-binding
      protein.
AB  - Rat liver mannose-binding protein (MBP-C) is the smallest known member of the
      collectin family of animal lectins, many of which are involved in defence against
      microbial pathogens. It consists of an N-terminal collagen-like domain linked to
      C-terminal carbohydrate-recognition domains. MBP-C, overproduced in Chinese
      hamster ovary cells, is post-translationally modified and processed in a manner
      similar to the native lectin. Analytical ultracentrifugation experiments indicate
      that MBP-C is trimeric, with a weight-averaged molecular mass of approx. 77 kDa.
      The rate of sedimentation of MBP-C and its mobility on gel filtration suggest a
      highly elongated molecule. Anomalous behaviour on gel filtration due to this
      extended conformation may explain previous suggestions that MBP-C forms a higher
      oligomer. The polypeptide chains of the MBP-C trimer are linked by disulphide
      bonds between two cysteine residues at the N-terminal junction of the collagen
      like domain. Analysis of an N-terminal tryptic fragment reveals that the
      disulphide bonding in MBP-C is heterogeneous and asymmetrical. These results
      indicate that assembly of MBP-C oligomers probably proceeds in a C- to N-terminal
      direction: trimerization at the C-terminus is followed by assembly of the
      collagenous domain and finally formation of N-terminal disulphide bonds. The
      relatively simple organization of MBP-C provides a template for understanding
      larger, more complex collectins.

PMID- 9230119
TI  - Influence of systematic error on the shape of the scatchard plot of tRNAPhe
      binding to eukaryotic ribosomes.
AB  - Scatchard plots of tRNAPhe binding to poly(U)-programmed human 80 S ribosomes can
      be curved, either concave upwards or concave downwards, depending on the
      experimental conditions. The influence of a systematic error on the shape of the
      Scatchard plots has been analysed in a model experiment where the binding
      proceeds at two independent sites. The Scatchard plot for this binding model has
      a concave-upwards shape. When the concentration of the ribosomes is kept
      constant, a small systematic error in tRNA concentration changes this Scatchard
      plot markedly to a concave-downwards plot as though a co-operative interaction
      occurred. In contrast, when the tRNA concentration exceeds the ribosomal
      concentration and their concentration ratio is constant, the Scatchard plot is
      stable with respect to the systematic error. We suggest the latter type of
      experiment to be more appropriate. The results also imply a non-co-operative
      interaction of tRNAPhe with the 80 S ribosome.

PMID- 9230120
TI  - Multiple C-terminal serine phosphorylation accompanies both protein kinase C
      dependent and -independent activation of cytosolic 85 kDa phospholipase A2 in
      macrophages.
AB  - Exposure of mouse macrophages to either phorbol ester or certain bacteria was
      previously shown to cause increased phosphorylation of the cytosolic 85 kDa
      phospholipase A2 as well as a stable increase in its catalytic activity. We have
      now attempted to map the major phosphorylation sites on the enzyme in such cells.
      Phosphorylation occurred on serine residues without a detectable increase in
      either phosphothreonine or phosphotyrosine. After CNBr cleavage five fragments
      showed increased 32P labelling. Among those the most heavily labelled fragment
      was identified as the most C-terminal (residues 698-749), containing six serine
      residues. This was true whether phorbol ester or bacteria, causing protein kinase
      C-independent phospholipase A2 activation, was used as stimulus. The heavy
      phosphorylation of the most C-terminal fragment and an analysis of tryptic
      peptides derived from it suggested that more than one of the six serine residues
      became phosphorylated. Smaller increases also occurred in other CNBr-cleaved
      fragments from the C-terminal part of the protein, including that carrying Ser
      505, a known target of the mitogen-activated protein kinase ERK-2 (extracellular
      signal regulated kinase). Dexamethasone treatment (1-100 nM for 20 h), which was
      earlier shown to dose-dependently down-regulate the 85 kDa phospholipase A2 and
      its activation by phorbol ester and zymosan, was here shown also to counteract
      the protein kinase C-independent activation and arachidonate release elicited by
      bacteria. It remains to be determined whether all phosphorylation sites are
      equally affected under those conditions.

PMID- 9230121
TI  - Activation of sea-urchin sperm motility is accompanied by an increase in the
      creatine kinase exchange flux.
AB  - The kinetics of the creatine kinase (CK) reaction were studied in suspensions of
      quiescent and active, intact sea-urchin spermatozoa in artificial seawater, using
      31P-NMR magnetization transfer. In inactive sperm, no CK-mediated exchange flux
      was detected, whereas in activated motile sperm, the forward pseudo-first-order
      rate constant was 0.13+/-0.04 s-1 at 10 degrees C, corresponding to a steady
      state CK flux of 3.1+/-0.5 mM.s-1. Intracellular pH shifted from 6.6+/-0.1 to
      7.6+/-0.1 upon activation. The phosphocreatine (PCr)/ATP and PCr/Pi ratios were
      only marginally reduced in activated sperm, whereas the estimated cytosolic free
      ADP concentration increased remarkably from 9 microM in quiescent, to 114 microM
      in activated spermatozoa. The elevation of CK flux upon sperm activation is
      discussed in the light of the proposition that in sea-urchin spermatozoa, which
      are fuelled entirely by oxidative phosphorylation, high-energy phosphate
      transport is mediated by a 'CK/PCr shuttle'.

PMID- 9230122
TI  - Glutathione conjugation of chlorambucil: measurement and modulation by plant
      polyphenols.
AB  - Chlorambucil (CMB), an anticancer drug, was cytotoxic at concentrations of 5-20
      microM to human colon adenocarcinoma cells. It inhibited [14C]thymidine uptake in
      a dose-dependent manner. Both effects were potentiated by simultaneous exposure
      of the cells to 10 microM plant polyphenols. In an attempt to explain the
      possible mechanism of action of the polyphenols in relation to these
      observations, an HPLC-radiometric method was developed to measure the conjugation
      of CMB with glutathione in these cells and to monitor the export of
      monochloromonoglutathionyl CMB (MG-CMB), its main glutathione conjugate. At
      micromolar concentrations, five polyphenols, namely quercetin, butein, tannic
      acid, 2'-hydroxychalcone and morin, inhibited the efflux of CMB significantly; an
      inhibition of 40% was observed with 10 microM quercetin. The glutathione S
      transferase (GST) activity of the cancer cells, measured with 1-chloro-2,4
      dinitrobenzene, was also inhibited by the polyphenols. Their combined action on
      GST and on the efflux of MG-CMB conjugate could provide an enhanced positive
      modulation of sensitivity of the tumour cells to CMB.

PMID- 9230123
TI  - Fatty acyl-CoA-acyl-CoA-binding protein complexes activate the Ca2+ release
      channel of skeletal muscle sarcoplasmic reticulum.
AB  - We previously reported that fatty acyl-CoA esters activate ryanodine
      receptor/Ca2+ release channels in a terminal cisternae fraction from rabbit
      skeletal muscle [Fulceri, Nori, Gamberucci, Volpe, Giunti and Benedetti (1994)
      Cell Calcium 15, 109-116]. Skeletal muscle cytosol contains a high-affinity fatty
      acyl-CoA-binding protein (ACBP) [Knudsen, Hojrup, Hansen, H.O., Hansen, H.F. and
      Roepstorff (1989) Biochem. J. 262, 513-519]. We show here that palmitoyl-CoA
      (PCoA) in a complex with a molar excess of bovine ACBP causes a discrete Ca2+
      efflux or allows Ca2+ release from the Ca2+-preloaded terminal cisternae fraction
      by sub-optimal caffeine concentrations. Both effects were abolished by elevating
      the free [Mg2+] in the system, which inhibits the Ca2+ release channel activity.
      Sensitization towards caffeine was a function of both the concentration of the
      complex and the [PCoA]-to-[ACBP] ratio. In all experimental conditions the
      calculated free [PCoA] was no more than 50 nM, and such concentrations by
      themselves were inactive on Ca2+ release channels. The KD for PCoA binding was
      approx. 2 nM for bovine and yeast ACBP, and slightly higher (8 nM) for rat ACBP.
      The PCoA-rat ACBP complex behaved in the same manner as the PCoA-bovine ACBP
      complex, whereas the ester complexed with yeast ACBP was more active in
      activating/sensitizing Ca2+ efflux. A non-hydrolysable analogue of PCoA bound to
      (bovine) ACBP also sensitized the Ca2+ release channel towards caffeine. These
      findings indicate that fatty acyl-CoA-ACBP complexes either interact directly
      with one or more components in the terminal cisternae membranes or, through
      interaction with the component(s), donate the fatty acyl-CoA esters to high
      affinity binding sites of the membrane, thus affecting (and possibly regulating)
      Ca2+ release channel activity.

PMID- 9230124
TI  - Perfluorodecanoic acid enhances the formation of oleic acid in rat liver.
AB  - The feeding of perfluorodecanoic acid (PFDA) to male rats at a dietary
      concentration of 0.005% (w/w) for 7 days resulted in a marked increase in the
      activity of microsomal stearoyl-CoA desaturation in the liver. This increase in
      the overall desaturation activity was due to the induction of terminal desaturase
      among the components comprising the desaturation system. In contrast, PFDA
      inhibited desaturation in vitro, seemingly due to interference with electron
      transport through the desaturation system. Accordingly, PFDA can be an inducer
      and also an inhibitor of delta9-desaturation. PFDA feeding enhanced the
      conversion of radioactive stearic acid into oleic acid in the liver in vivo,
      indicating that the induction of delta9-desaturase by PFDA functions in vivo.
      PFDA feeding increased the mass of octadecenoic acid (C18:1) in the liver and the
      proportion of C18:1 in microsomal lipid. A highly significant linear correlation
      existed between the microsomal desaturase activity and the proportion of C18:1 in
      microsomal lipid when compared using rats in five different physiological states:
      control, PFDA-fed, p-chlorophenoxyisobutyric acid (clofibric acid)-fed, starved
      and starved/refed. These results suggest that the increase in the hepatic level
      of C18:1 caused by feeding of PFDA to rats can be explained by the common concept
      of regulation, i.e. the hepatic level of C18:1 is under the control of delta9
      desaturase. The dietary administration of PFDA also increased the content of
      cytochrome P-450 and the activity of 7-ethoxycoumarin O-de-ethylase in the liver.

PMID- 9230125
TI  - Stimulation of DNA synthesis by natural ceramide 1-phosphate.
AB  - We found that natural (long-chain) ceramide 1-phosphate can be dispersed into
      aqueous solution when dissolved in an appropriate mixture of methanol/dodecane
      (49:1, v/v). This solvent mixture facilitates the interaction of this
      phosphosphingolipid with cells. Under these conditions, incubation of EGFR T17
      fibroblasts with natural ceramide 1-phosphate caused a potent stimulation of DNA
      synthesis. This effect was accompanied by an increase in the levels of
      proliferating-cell nuclear antigen. Concentrations of natural ceramide 1
      phosphate that stimulated the synthesis of DNA did not inhibit adenylate cyclase
      activity, nor did they stimulate phospholipase D. Natural ceramide 1-phosphate
      did not alter the cellular phosphorylation state of tyrosine residues or of
      mitogen-activated protein kinase. Furthermore, natural ceramide 1-phosphate
      failed to induce the expression of the proto-oncogenes c-myc and c-fos. Both the
      stimulation of DNA synthesis and the induction of proliferating-cell nuclear
      antigen by natural ceramide 1-phosphate were inhibited by natural ceramides. This
      work suggests that the use of methanol and dodecane to deliver natural ceramide 1
      phosphate to cells may be useful for elucidation of the biological function(s)
      and mechanism(s) of action of ceramide 1-phosphate.

PMID- 9230126
TI  - Description of a novel eukaryotic deoxyuridine 5'-triphosphate
      nucleotidohydrolase in Leishmania major.
AB  - A Leishmania major full-length cDNA encoding a functional dUTP
      nucleotidohydrolase (dUTPase; EC 3.6.1.23) was isolated from a cDNA expression
      library by genetic complementation of dUTPase deficiency in Escherichia coli. The
      cDNA contained an open reading frame that encoded a protein of 269 amino acid
      residues with a calculated molecular mass of 30.3 kDa. Although eukaryotic
      dUTPases exhibit extensive similarity and there are five amino acid motifs that
      are common to all currently known dUTPase enzymes, the sequence of the protozoan
      gene differs significantly from its eukaryotic counterparts. None of the
      characteristic motifs were readily identifiable and the sequence encoded a larger
      polypeptide. However, the products of the reaction were dUMP and PPi, competition
      experiments with other deoxyribonucleoside triphosphates showed that the reaction
      is specific for dUTP, and the protozoan gene complemented dUTPase deficiency in
      Escherichia coli. The gene is of single copy; Northern blots indicated a
      transcript of the same size as the cDNA isolated in the screening procedure. The
      enzyme can be efficiently overexpressed in a highly active form by using the
      expression vector pET-11c. The availability of recombinant enzyme in large
      quantities will now permit detailed mechanistic and structural studies, which
      might contribute to a rational design of specifically targeted inhibitors against
      dUTPase from L. major.

PMID- 9230127
TI  - Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein
      kinase cascade and functional activation of SHP-1 tyrosine phosphatase.
AB  - Angiotensin II type 2 (AT2) receptors are involved in the inhibition of cell
      proliferation as well as in apoptosis and neuronal differentiation, through
      intracellular signalling pathways that remain poorly defined. The present study
      examines the effect of AT2-receptor stimulation on growth-factor-induced pathways
      leading to the activation of mitogen-activated protein (MAP) kinases. In N1E-115
      neuroblastoma cells, AT2 receptors inhibit the activity of MAP kinases induced by
      serum as well as by epidermal growth factor. The inhibitory effect of angiotensin
      II (Ang II) is rapid and transient, and affects both ERK1 and ERK2 (extracellular
      signal-related protein kinase) isoforms of the enzyme. AT2-mediated MAP kinase
      inactivation is not sensitive to pertussis toxin or okadaic acid, but involves a
      vanadate-sensitive protein tyrosine phosphatase (PTP). Expression of MAP kinase
      phosphatase-1 (MKP-1) is not significantly modified upon AT2-receptor activation,
      and insensitivity to actinomycin D also rules out transcriptional induction of
      other MKPs as a possible mechanism for AT2-mediated inactivation of MAP kinases.
      In addition, we report here that both in N1E-115 cells and in Chinese hamster
      ovary cells expressing recombinant human AT2 receptors, Ang II rapidly stimulates
      the catalytic activity of SHP-1, a soluble PTP that has been implicated in
      termination of signalling by cytokine and growth-factor receptors. These findings
      thus demonstrate functional negative cross-talk between heptahelical AT2
      receptors and receptor tyrosine kinases, and suggest that SHP-1 tyrosine
      phosphatase is an early transducer of the AT2 receptor signalling pathway.

PMID- 9230129
TI  - Rabbit DNase I: purification from urine, immunological and proteochemical
      characterization, nucleotide sequence, expression in tissues, relationships with
      other mammalian DNases I and phylogenetic analysis.
AB  - DNase I from rabbit urine was purified approx. 3600-fold to apparent homogeneity
      with a 41% yield by affinity chromatography utilizing DNA-cellulose; the purity
      of the final preparation was assessed by SDS/PAGE, lack of contamination by other
      nucleases and production of a monospecific antibody against the enzyme. Although
      the proteochemical and enzymological properties of the purified enzyme resembled
      those of other mammalian DNases I, the enzymic activity of rabbit DNase I was
      less efficiently inhibited by monomeric actin than was that of human DNase I,
      probably due to substitution of an amino acid residue involved in actin binding
      (Tyr-65 to Phe). The effects of specific antibodies to human, rabbit and rat
      DNases I on the activities of the corresponding purified enzymes revealed that
      human DNase I lies between the rat and rabbit enzymes with regard to its
      immunological properties. An 1158 bp full-length cDNA encoding rabbit DNase I was
      constructed from the total RNA of rabbit pancreas using a combination of reverse
      transcriptase-PCR and rapid amplification of cDNA ends, followed by sequencing.
      This identified a 17- or 21-amino-acid signal sequence, with the mature enzyme
      containing 260 amino acids and a single N-glycosylation site at Asn-18. The amino
      acid sequence deduced from the cDNA sequence exactly matched that determined
      proteochemically from the purified enzyme up to residue 20. A systematic survey
      of DNase I distribution as measured by both enzymic activity and DNase I gene
      transcripts in 12 rabbit tissues showed the pancreas and parotid gland to produce
      equivalent levels, higher than those in other tissues. Enzymic activity and DNase
      I gene expression levels in each tissue correlated well. The results of
      phylogenetic and sequence identity analysis, immunological properties and tissue
      distribution patterns of DNase I indicated a closer relationship between the
      rabbit and human enzymes than for other mammalian DNases I. Furthermore,
      differences between the enzymic activities expressed in mammalian parotid gland
      and pancreas suggest that the distribution of DNase I in mammalian tissue is
      species-specific.

PMID- 9230130
TI  - Synthetic putative transmembrane region of minimal potassium channel protein
      (minK) adopts an alpha-helical conformation in phospholipid membranes.
AB  - Minimal potassium channel protein (minK) is a potassium channel protein
      consisting of 130 amino acids, possessing just one putative transmembrane domain.
      In this study we have synthesized a peptide with the amino acid sequence
      RDDSKLEALYILMVLGFFGFFTLGIMLSYI, containing the putative transmembrane region of
      minK, and analysed its secondary structure by using Fourier-transform IR and CD
      spectroscopy. The peptide was virtually insoluble in aqueous buffer, forming
      intermolecular beta-sheet aggregates. On attempted incorporation of the peptide
      into phospholipid membranes with a method involving dialysis, the peptide adopted
      a predominantly intermolecular beta-sheet conformation identical with that of the
      peptide in aqueous buffer, in agreement with a previous report [Horvath,
      Heimburg, Kovachev, Findlay, Hideg and Marsh, (1995) Biochemistry 34, 3893-3898].
      However, by using an alternative method of incorporating the peptide into
      phospholipid membranes we found that the peptide adopted a predominantly alpha
      helical conformation, a finding consistent with various proposed structural
      models. These observed differences in secondary structure are due to artifacts of
      aggregation of the peptide before incorporation into lipid.

PMID- 9230128
TI  - Ca2+-dependent interaction of the growth-associated protein GAP-43 with the
      synaptic core complex.
AB  - The synaptic vesicle exocytosis occurs by a highly regulated mechanism: syntaxin
      and 25 kDa synaptosome-associated protein (SNAP-25) are assembled with vesicle
      associated membrane protein (VAMP) to form a synaptic core complex and then
      synaptotagmin participates as a Ca2+ sensor in the final step of membrane fusion.
      The 43 kDa growth-associated protein GAP-43 is a nerve-specific protein that is
      predominantly localized in the axonal growth cones and presynaptic terminal
      membrane. In the present study we have examined a possible interaction of GAP-43
      with components involved in the exocytosis. GAP-43 was found to interact with
      syntaxin, SNAP-25 and VAMP in rat brain tissues and nerve growth factor
      dependently differentiated PC12 cells, but not in undifferentiated PC12 cells.
      GAP-43 also interacted with synaptotagmin and calmodulin. These interactions of
      GAP-43 could be detected only when chemical cross-linking of proteins was
      performed before they were solubilized from the membranes with detergents, in
      contrast with the interaction of the synaptic core complex, which was detected
      without cross-linking. Experiments in vitro showed that the interaction of GAP-43
      with these proteins occurred Ca2+-dependently; its maximum binding with the core
      complex was observed at 100 microM Ca2+, whereas that of syntaxin with
      synaptotagmin was at 200 microM Ca2+. These values of Ca2+ concentration are
      close to that required for the Ca2+-dependent release of neurotransmitters.
      Furthermore we observed that the interaction in vitro of GAP-43 with the synaptic
      core complex was coupled with protein kinase C-mediated phosphorylation of GAP
      43. Taken together, our results suggest a novel function of GAP-43 that is
      involved in the Ca2+-dependent fusion of synaptic vesicles.

PMID- 9230131
TI  - Subunit diversity and tissue distribution of human glutathione S-transferases:
      interpretations based on electrospray ionization-MS and peptide sequence-specific
      antisera.
AB  - Uncertainties about the composition and identities of glutathione S-transferases
      (GSTs) in human tissue have impeded studies on their biological functions. A
      rigorous protocol has therefore been developed to characterize the human
      proteins. Cytosolic GST subunits were resolved by reverse-phase HPLC methods,
      individual components were assigned to Alpha, Mu and Pi classes on the basis of
      their immunoreactivities, and peptide-sequence-specific antisera were used to
      distinguish among five different Mu-class subunits (GSTM1-GSTM5). Each subunit
      type was characterized and identified unambiguously by electrospray ionization
      MS. Acetylation of N-terminal residues in the GSTA1, GSTA2, GSTM3 and GSTM4
      subunits were the only natural post-translational modifications detected. The
      unique structure of GSTM3, with N- and C-terminal peptide extensions predicted
      from cDNA sequences, was confirmed. Only testis and brain were rich sources of
      GSTM3 subunits. Subunit profiles were distinct and characteristic of the
      particular tissue type, and this tissue specificity in GST expression was evident
      even in organs from different individuals. For instance, livers had relatively
      simple GST compositions, consisting of a preponderance of Alpha-class subunits
      and GSTM1 (when present). By contrast, representation of most subunit types was a
      characteristic feature of testis, which had the highest levels of GSTs. GSTM4 and
      GSTM5 subunits, here identified for the first time in human tissue extracts, were
      minor components, with GSTM5 found only in brain, lung and testis. Specimens
      devoid of GSTM1 subunits, particularly those from null-genotype individuals, were
      readily discerned at the protein level. Liver was the only rich source of the
      GSTM1 subunit (although it also constituted a major fraction of adrenal GSTs),
      and so the functional consequences of the GSTM1 gene deletion are likely to vary
      in extrahepatic tissues.

PMID- 9230132
TI  - Cytokines modulate glucose transport in skeletal muscle by inducing the
      expression of inducible nitric oxide synthase.
AB  - The principal goal of the present study was to test the hypothesis that cytokines
      modulate glucose transport in skeletal muscle by increasing nitric oxide
      production. Cultured L6 skeletal muscle cells were incubated in the presence of
      tumour necrosis factor-alpha, interferon-gamma or lipopolysaccharide (LPS) alone
      or in combination for 24 h. Neither cytokines nor LPS alone induced NO
      production, as measured by nitrite concentrations in the medium. However, when
      used in combination, the two cytokines significantly stimulated NO production,
      and this effect was synergistically enhanced by the presence of LPS. Reverse
      transcriptase-PCR (RT-PCR) analysis revealed that NO release was associated with
      the induction of inducible (macrophage-type) NO synthase (iNOS). The increase in
      iNOS expression was confirmed at the protein level by Western-blot analysis and
      NADPH/diaphorase histochemical staining. Cytokines and LPS markedly increased
      basal glucose transport in L6 myocytes. Insulin also stimulated basal glucose
      transport, but significantly less in cells chronically exposed to cytokines/LPS.
      The sensitivity of L6 muscle cells to insulin-stimulated glucose transport was
      also significantly decreased by cytokines/LPS treatment. The NOS inhibitor NG
      nitro-l-arginine methyl ester (l-NAME) inhibited nitrite production in
      cytokine/LPS-treated cells, and this prevented the increase in basal glucose
      transport and restored muscle cell responsiveness to insulin. Cytokines/LPS
      exposure significantly increased GLUT1 transporter protein levels but decreased
      GLUT4 expression in L6 cells. l-NAME treatment prevented the increase in GLUT1
      protein content but failed to restore GLUT4 transporter levels. These results
      demonstrate that cytokines and LPS affect glucose transport and insulin action by
      inducing iNOS expression and NO production in skeletal muscle cells. The data
      further indicate that cytokines and LPS increase the expression of the GLUT1
      transporter protein by an NO-dependent mechanism.

PMID- 9230133
TI  - Low concentrations of lipid hydroperoxides prime human platelet aggregation
      specifically via cyclo-oxygenase activation.
AB  - There is mounting evidence that lipid peroxides contribute to pathophysiological
      processes and can modulate cellular functions. The aim of the present study was
      to investigate the effects of lipid hydroperoxides on platelet aggregation and
      arachidonic acid (AA) metabolism. Human platelets, isolated from plasma, were
      incubated with subthreshold (i.e. non-aggregating) concentrations of AA in the
      absence or presence of hydroperoxyeicosatetraenoic acids (HPETEs). Although
      HPETEs alone had no effect on platelet function, HPETEs induced the aggregation
      of platelets co-incubated with non-aggregating concentrations of AA, HPETEs being
      more potent than non-eicosanoid peroxides. The priming effect of HPETEs on
      platelet aggregation was associated with an increased formation of cyclo
      oxygenase metabolites, in particular thromboxane A2, and was abolished by
      aspirin, suggesting an activation of cyclo-oxygenase by HPETEs. It was not
      receptor-mediated because the 12-HPETE-induced enhancement of AA metabolism was
      sustained in the presence of SQ29, 548 or RGDS, which blocked the aggregation.
      These results indicate that physiologically relevant concentrations of HPETEs
      potentiate platelet aggregation, which appears to be mediated via a stimulation
      of cyclo-oxygenase activity.

PMID- 9230134
TI  - Electrogenic H+ pathway contributes to stimulus-induced changes of internal pH
      and membrane potential in intact neutrophils: role of cytoplasmic phospholipase
      A2.
AB  - The potential role of cytosolic phospholipase A2 (cPLA2) in the regulation of the
      electrogenic arachidonic acid (AA)-activatable H+ translocator of neutrophils was
      investigated. (1) The trifluoromethyl ketone analogue of arachidonate (AACOCF3),
      a newly developed selective blocker of cPLA2, inhibited both the N
      formylmethionyl-leucylphenylalanine (fMLP)- and the phorbol-ester-induced
      rheogenic H+ efflux (K0.5 approximately 5 microM) and abrogated the stimulus
      triggered release of AA from these cells. The drug failed to reduce the fMLP
      evoked Ca2+ signal or protein tyrosine phosphorylation and did not affect the
      activity of protein kinase C. By using the patch-clamp technique we verified that
      the agent did not interfere with the voltage- and the pH-dependent activation of
      the H+ conductance of the peritoneal macrophages and therefore is not a direct
      blocker of the H+ channel itself. AACOCF3, however, slightly decreased the AA
      induced stimulation of the H+ currents. We conclude that AA, liberated by the
      agonist-induced stimulation of cPLA2, is a direct activator of H+ conductance.
      (2) AACOCF3 did not inhibit superoxide generation, indicating that activation of
      cPLA2 may not be a prerequisite for turning on NADPH oxidase. (3) Since neither
      acid generation by the oxidase, nor the basal or stimulated Na+/H+ exchange (the
      predominant acid-eliminating mechanism) were influenced by the drug, we could use
      AACOCF3 to address whether the H+ channel in fact opens and plays any
      physiological role during activation of neutrophils. Stimulus-induced cytosolic
      alkalinization was smaller, whereas depolarization became larger, in the presence
      of AACOCF3. Stimulated H+ conductance therefore does contribute to intracellular
      pH (pHi) homoeostasis and membrane potential changes of intact neutrophils.

PMID- 9230135
TI  - Evidence for interaction of the fusion protein alpha-SNAP with membrane lipid.
AB  - alpha-SNAP [soluble N-ethylmaleimide-sensitive fusion protein (NSF)-attachment
      protein] is required for fusion of transport vesicles with their target membrane.
      In this study, we have examined the membrane-binding properties of alpha-SNAP. We
      have found that in several tissues a much larger amount of alpha-SNAP per unit
      weight of protein is bound to membranes than is free in the cytosol. Biochemical
      analysis shows that a fraction of alpha-SNAP behaves in ways characteristic of
      hydrophobic, lipid-associated proteins. These findings suggest that membrane
      binding may be accounted for, at least in part, by interaction with membrane
      lipid. Consistent with this idea, binding of newly synthesized alpha-SNAP to
      brain membranes was found to be independent of functional SNAP receptors and
      could be accounted for by direct binding of alpha-SNAP to membrane lipid.
      Furthermore, membrane lipid enhanced the ability of alpha-SNAP to stimulate NSF
      dependent ATPase activity.

PMID- 9230137
TI  - Purification and characterization of three distinct types of phospholipase A2
      inhibitors from the blood plasma of the Chinese mamushi, Agkistrodon blomhoffii
      siniticus.
AB  - Three distinct types of phospholipase A2 (PLA2) inhibitory proteins (PLIalpha,
      PLIbeta, and PLIgamma) were isolated from the blood plasma of the Chinese
      mamushi, Agkistrodon blomhoffii siniticus. PLIalpha is an inhibitor that we have
      already purified and whose amino acid sequence we have already determined
      [Ohkura, Inoue, Ikeda and Hayashi (1993) J. Biochem. (Tokyo) 113, 413-419]. It
      inhibited selectively the group-II acidic PLA2s from Crotalidae venom. PLIbeta
      was a 160-kDa glycoprotein having a trimeric structure composed of 50-kDa
      subunits. The amino acid sequence of the first 30 amino acids of the N-terminal
      part of the 50-kDa subunit was determined and found to have no significant
      homology to that of known proteins. PLIbeta was a selective inhibitor against the
      group-II basic PLA2s from Crotalidae venom. Some amino acid residues located in
      or close to the interfacial binding surface of the group-II basic PLA2s were
      suggested to be involved in selective binding to PLIbeta. PLIgamma was a 100-kDa
      glycoprotein containing 25-kDa and 20-kDa subunits and inhibited all of the PLA2s
      investigated equally, including Elapidae venom PLA2s (group I), Crotalidae and
      Viperidae venom PLA2s (group II) and honey-bee PLA2 (group III). From the N
      terminal sequences of the two subunits, PLIgamma was found to be the same type of
      PLI that had been purified from Thailand cobra plasma.

PMID- 9230136
TI  - Inhibition of glycerol metabolism in hepatocytes isolated from endotoxic rats.
AB  - Sepsis or endotoxaemia inhibits gluconeogenesis from various substrates, the main
      effect being related to a change in the phosphoenolpyruvate carboxykinase
      transcription rate. In addition, sepsis has been reported to affect the oxidative
      phosphorylation pathway. We have studied glycerol metabolism in hepatocytes
      isolated from rats fasted and injected 16 h previously with lipopolysaccharide
      from Escherichia coli. Endotoxin inhibited glycerol metabolism and led to a very
      large accumulation of glycerol 3-phosphate; the cytosolic reducing state was
      increased. Furthermore glycerol kinase activity was increased by 33% (P<<0.01).
      The respiratory rate of intact cells was significantly decreased by sepsis, with
      glycerol or octanoate as exogenous substrates, whereas oxidative phosphorylation
      (ATP-to-O ratio or respirations in state 4, state 3 and the oligomycin
      insensitive state as well as the uncoupled state) was unchanged in permeabilized
      hepatocytes. Hence the effect on energy metabolism seems to be present only in
      intact hepatocytes. An additional important feature was the observation of a
      significant increase in cellular volume in cells from endotoxic animals, which
      might account for the alterations induced by sepsis.

PMID- 9230138
TI  - Preservation of the native structure and function of Ca2+-ATPase from
      sarcoplasmic reticulum: solubilization and reconstitution by new short-chain
      phospholipid detergent 1,2-diheptanoyl-sn-phosphatidylcholine.
AB  - The properties of Ca2+-ATPase purified and reconstituted from rabbit skeletal
      sarcoplasmic reticulum (SR) has been studied in comparison with the preparations
      obtained by the commonly used detergent poly(oxyethylene)8-lauryl ether (C12E8)
      and the bile salt detergents cholate and deoxycholate. 1,2-Diheptanoyl-sn
      phosphatidylcholine (DHPC) has been shown to be excellent for solubilizing a wide
      variety of membrane proteins [Kessi, Poiree, Wehrli, Bachofen, Semenza and Hauser
      (1994) Biochemistry 33, 10825-10836]. The DHPC method consistently gave higher
      yields of purified Ca2+-ATPase with a greater specific activity than the methods
      with C12E8, cholate, or deoxycholate. DHPC and C12E8 were superior to cholate and
      deoxycholate in active enzyme yields and specific activity. DHPC-solubilized Ca2+
      ATPase purified on a density gradient retained the E1Ca-E1(*)Ca conformational
      transition, whereas the enzyme from the C12E8 purification did not retain this
      transition. The coupling of Ca2+ transported to ATP hydrolysed in the DHPC
      purified enzyme was maximal and matched the values obtained with native SR,
      whereas the coupling was much lower for the C12E8-purified enzyme. The specific
      activity of Ca2+-ATPase reconstituted into dioleoylphosphatidylcholine vesicles
      with DHPC was up to 2-fold greater than that achieved with C12E8, and is
      comparable to that measured in the native SR. Finally, the dissociation of Ca2+
      ATPase into monomers by DHPC preserved the ATPase activity, whereas similar
      dissociation by C12E8 gave only one-sixth the activity of that obtained with
      DHPC. These studies show that the Ca2+-ATPase solubilized, purified and
      reconstituted with DHPC is superior to that obtained with C12E8 in significant
      ways, making it a preparation suitable for detailed studies on the mechanism of
      ion transport and the role of protein-lipid interactions in the function of
      membrane proteins.

PMID- 9230139
TI  - Regulation by phosphorylation of Xenopus laevis poly(ADP-ribose) polymerase
      enzyme activity during oocyte maturation.
AB  - Poly(ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme that is
      dependent on DNA breaks and nicks for its enzyme activity. These DNA nicks and
      breaks function as allosteric effectors of the enzyme activity. This reaction is
      important for efficient DNA base excision repair, although it is not a component
      of the elementary repair pathway itself. The physiological relevance of this
      reaction might be to ensure correct and efficient DNA repair. We have examined
      the enzyme activity of PARP in oocytes and eggs of Xenopus laevis. Although both
      oocytes and eggs contain approximately the same amounts of enzyme protein, there
      is no detectable enzyme activity in the oocytes, whereas in the eggs the enzyme
      is active. Enzyme activity appears during oocyte maturation, approx. 4 h after
      induction by progesterone. This enzyme activation coincides with the appearance
      of active maturation-promoting factor. Enzyme activation is accompanied by a
      shift in the electrophoretic mobility of the polypeptide, from an apparent
      molecular mass of 116 kDa to 125 kDa. Treatment with either bacterial or potato
      phosphatase reverses the mobility shift and abolishes enzyme activity. Incubation
      of maturing X. laevis eggs with radioactive inorganic phosphate and subsequent
      immunoprecipitation demonstrate that the PARP protein is phosphorylated in vivo.
      We show that maturation-promoting factor (Cyclin B/cdc2) cannot itself be
      responsible for the phosphorylation and activation of PARP in maturing X. laevis
      eggs. Together, these results demonstrate that the enzyme activity of PARP in X.
      laevis oocytes and eggs is regulated by post-translational, covalent
      phosphorylation.

PMID- 9230140
TI  - N-6 and n-3 polyunsaturated fatty acids stimulate translocation of protein kinase
      Calpha, -betaI, -betaII and -epsilon and enhance agonist-induced NADPH oxidase in
      macrophages.
AB  - The polyunsaturated fatty acids (PUFA), arachidonic acid (AA), eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) were poor inducers of oxygen-dependent
      respiratory activity (chemiluminescence) in human monocytes and macrophages, but
      markedly enhanced the response to the tripeptide, N-formylmethionyl-leucyl
      phenylalanine. The effects of these fatty acids were seen at concentrations of 1
      microg/ml. A similar enhancement was seen with PMA, a stimulus that acts on
      protein kinase C (PKC), or calcium ionophore (A23187), which increases
      intracellular calcium, suggesting that the effect of the fatty acids was post
      surface receptor binding. HL-60 cells, differentiated to macrophage-like cells by
      culture in the presence of vitamin D3, were similarly affected by the fatty
      acids. In experiments in which the time of pre-exposure of the monocytes to PUFA
      was varied, it was found that the priming effect induced by AA, EPA and DHA was
      maximal at 5 min. The ability of these fatty acids to synergize with other
      agonists was completely lost if the fatty acids were either methylated or
      oxidized to the hydro and hydroperoxy derivatives. Saturated fatty acids were
      inactive. Western blot analysis demonstrated that the PUFA induced the
      translocation of PKCalpha, -betaI, -betaII and -epsilon isoenzymes to a
      particulate fraction. The synergistic response between fatty acids and A23187 was
      completely inhibited by pretreating the cells with a PKC inhibitor, GF-109203X,
      or by pretreatment of monocytes with PMA for 18 h, to deplete PKC levels. From
      these investigations it is evident that PUFA prime macrophages, causing
      increased/synergistic oxidative respiratory burst activity to other stimuli and
      that this priming is dependent on PKC translocation and activation.

PMID- 9230142
TI  - Competitive reverse-transcriptase PCR: a useful alternative to northern blotting
      for quantitative estimation of relative abundances of specific mRNAs in precious
      samples.

PMID- 9230141
TI  - Two Rab proteins, vesicle-associated membrane protein 2 (VAMP-2) and secretory
      carrier membrane proteins (SCAMPs), are present on immunoisolated parietal cell
      tubulovesicles.
AB  - The tubulovesicles of gastric parietal cells sequester H+/K+-ATPase molecules
      within resting parietal cells. Stimulation of parietal cell secretion elicits
      delivery of intracellular H+/K+-ATPase to the apically oriented secretory
      canaliculus. Previous investigations have suggested that this process requires
      the regulated fusion of intracellular tubulovesicles with the canalicular target
      membrane. We have sought to investigate the presence of critical putative
      regulators of vesicle fusion on immunoisolated gastric parietal cell
      tubulovesicles. Highly purified tubulovesicles were prepared by gradient
      fractionation and immunoisolation on magnetic beads coated with monoclonal
      antibodies against the alpha subunit of H+/K+-ATPase. Western blot analysis
      revealed the presence of Rab11, Rab25, vesicle-associated membrane protein 2
      (VAMP-2) and secretory carrier membrane proteins (SCAMPs) on immunoisolated
      vesicles. The same cohort of proteins was recovered on vesicles immunoisolated
      with monoclonal antibodies against SCAMPs and VAMP-2. In contrast, whereas
      immunoreactivities for syntaxin 1A/1B and synaptosome-associated protein (SNAP
      25) were present in gradient-isolated vesicles, none of the immunoreactivity was
      associated with immunoisolated vesicles. The observation of VAMP-2 and two Rab
      proteins on immunoisolated H+/K+-ATPase-containing tubulovesicles supports the
      role for tubulovesicles in a regulated vesicle fusion process. In addition, the
      presence of SCAMPs along with Rab11 and Rab25 implicates the tubulovesicles as a
      critical apical recycling vesicle population.

PMID- 9230144
TI  - Intravascular ultrasound assessment of the prevalence and causes of angiographic
      "haziness" following high-pressure coronary stenting.
AB  - Haziness at sites of balloon angioplasty is believed to represent plaque
      fractures or platelet deposition. The etiology of haziness adjacent to coronary
      stents remains uncertain. This study examines the prevalence and etiology of
      "peri-stent" haziness following high-pressure deployment. Consecutive patients
      undergoing coronary stenting and intravascular ultrasound imaging were included.
      Haziness was defined as nonhomogeneous contrast density and/or indistinct vessel
      borders by consensus of 2 observers. Patients were excluded if angiography
      revealed an obvious cause of haziness (thrombus, dissection). Matched control
      segments without haziness were selected for comparison. The most diseased site
      within the reference segment was identified by ultrasound. Lumen and plaque
      areas, percent plaque area, and plaque echo density were assessed. Haziness was
      identified within 31 segments in 30 patients (15% of 201 angiograms examined). At
      hazy sites, ultrasound revealed a large percent plaque area in 15, dissections in
      14, and near-normal findings in 2 segments. In the absence of dissection, percent
      plaque area and lumen area step-down from the stent to the diseased reference
      were greater than controls (percent plaque area 64 +/- 12% vs 56 +/- 10%, p =
      0.04 and lumen step-down 35 +/- 20% vs 13 +/- 25%, p = 0.006). With dissections,
      percent plaque area and lumen step-down were not different from controls (p =
      0.13 and 0.30, respectively), but underlying plaques were more frequently
      echolucent (64% vs 23%, p = 0.02). Thus, in this study, peri-stent haziness was
      evident in 15% of patients after high-pressure coronary stent deployment.
      Etiologies identified by intravascular ultrasound included unrecognized reference
      plaque and angiographically occult dissections.

PMID- 9230143
TI  - Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to
      reduce low-density lipoprotein cholesterol <100 mg/dl in patients with
      hyperlipidemia and coronary artery disease.
AB  - The efficacy, safety, and tolerability of a moderate dose, 3-drug lipid-lowering
      regimen were evaluated among 29 male patients with hyperlipidemia and coronary
      artery disease. In an initial 12-month phase, regular niacin, 500 mg qid,
      lovastatin, 20 mg bid, and colestipol, 10 g/bid, were given with dose adjustment
      for lipid targets and side effects. This was followed by 2 random sequence
      crossover phases (8 months each) alternating regular niacin with a polygel
      controlled-release formulation of niacin for use in this regimen. Lipid,
      lipoprotein, apoprotein, and clinical chemistry determinations were obtained at
      baseline, during the initial phase, at the 2 crossover phases, and at 6 weeks
      after therapy. A final questionnaire queried specific side effects and overall
      preferences. Low-/high-density lipoprotein (LDL/HDL) changed from means of 215/46
      mg/dl at baseline, to 94/59 mg/dl after run-in, to 85/52 mg/dl after 8 months of
      controlled-release niacin, and to 98/56 mg/dl after 8 months of regular niacin
      (regular niacin vs controlled-release niacin, p <0.005/<0.05). The target of LDL
      < or = 100 mg/dl was achieved at 8 months by 83% of these patients with
      controlled-release niacin and by 52% with regular niacin (p <0.01). Compliance
      was 95% with controlled-release niacin versus 85% with regular niacin (p <0.001).
      The controlled-release niacin and regular niacin regimens did not differ in terms
      of uric acid, glucose, insulin, or asparate aminotransferase levels. Overall, 21%
      of patients called the 3 drugs "very easy" and 72% "fairly easy" to take. The
      controlled-release niacin-containing regimen was preferred by 21 patients and the
      regular niacin by 4. In conclusion, these regimens achieve striking lipid changes
      among hyperlipidemic patients. Controlled release is the preferred niacin
      preparation in terms of LDL reduction, compliance, patient preference, and
      achieving the National Cholesterol Education Program guideline of LDL < or = 100
      mg/dl. The 2 niacin preparations did not differ in evidence of toxicity.

PMID- 9230145
TI  - Frequency of family history of acute myocardial infarction in patients with acute
      myocardial infarction. Argentine FRICAS (Factores de Riesgo Coronario en America
      del Sur) Investigators.
AB  - The relation between family history of acute myocardial infarction (AMI) and the
      risk of AMI was analyzed using data of a case-control study conducted in
      Argentina between 1992 and 1994. Case patients were 1,060 subjects with AMI
      admitted to 35 coronary care units, and controls were 1,071 subjects admitted to
      the same network of hospitals where cases had been identified, for a wide
      spectrum of acute conditions unrelated to known or likely risk factors for AMI:
      31% of cases versus 15% of controls reported > or = 1 first-degree relative with
      history of AMI. Compared with subjects without family history of AMI, the odds
      ratio (OR) of AMI, after allowance for age, sex, cholesterolemia, smoking,
      diabetes, hypertension, body mass index, education, social class, and physical
      exercise, was 2.18 (95% confidence interval [CI] 1.74 to 2.74) for those with
      family history of AMI. The OR was 2.04 (95% CI 1.60 to 2.60) for subjects with 1
      relative, and 3.18 (95% C 1.86 to 5.44) for those reporting > or = 2 relatives
      with AMI. In women the OR for any family history of AMI was 2.83, and in men
      2.01. The association was of similar magnitude if the mother (OR 1.98), the
      father (OR 2.13), or a sibling (OR 2.48) had had an AMI. The association with
      family history was stronger at a younger age because the OR for subjects
      reporting > or = 2 more relatives with a history of AMI was 4.42 for subjects
      aged < 55 years, and 3.00 for those aged > or = 55 years. The association between
      AMI and family history of AMI was consistent across separate strata of education,
      social class, smoking, and serum cholesterol, but was less strong in subjects
      with history of diabetes and hypertension. When the interaction of known risk
      factors with family history of AMI was analyzed, hypercholesterolemia,
      hypertension, and smoking had approximately multiplicative effects on the
      relative risk. The OR was 4.50 for subjects with family history and cholesterol >
      or = 240 ml/dl, 4.52 for those with hypertension, and 5.77 for current smokers
      with family history of AMI. Thus, this study confirms that a family history of
      AMI is a strong and independent risk factor for AMI. In this population from
      Argentina, family history accounted for 14% of all cases of AMI in men and 26% in
      women.

PMID- 9230146
TI  - Nitroglycerin tolerance at the platelet level in patients with angina pectoris.
AB  - Suppression of platelet aggregation may be an important component of the
      therapeutic effect of nitroglycerin (NTG). Because of the phenomenon of
      hemodynamic tolerance to NTG, we tested the hypothesis that the anti-platelet
      effects of NTG in humans are also subject to tolerance induction. In patients
      with stable angina who had not received nitrates for at least 24 hours before
      study, sublingual administration of NTG (300 microg; n = 17) attenuated the
      reversal of adenosine diphosphate-induced platelet aggregation by NTG applied in
      vitro. Three minutes after in vivo NTG administration, concentration of NTG
      producing 50% reversal of aggregation (C50) increased from 7.9 +/- 1.9 x 10(-5)
      to 5.5 +/- 0.3 x 10(-4) M (p <0.01); this change persisted for at least 60
      minutes. There was no concomitant change in C50 values for sodium nitroprusside
      applied in vitro. Basal activity of platelet guanylate cyclase and its response
      to sodium nitroprusside were not affected after administration of NTG. Brief
      intravenous infusion of NTG (10 microg/min for 10 minutes) produced no
      significant changes in platelet responses to NTG in vitro. However, prolonged
      infusion of NTG (5 microg/min for 24 hours, patients with unstable angina
      pectoris, n = 11) caused suppression of in vitro platelet response to NTG.
      Platelets from patients receiving prophylactic nitrates (n = 19) were less
      responsive to the antiaggregatory effects of NTG in vitro than those from
      patients who had not received nitrates in the previous 24 hours (n = 21). Thus,
      clinical exposure to NTG, even in very low doses, induces tolerance to
      antiaggregatory effects of NTG. This phenomenon is not associated either with
      cross tolerance to sodium nitroprusside or with down-regulation of platelet
      guanylate cyclase.

PMID- 9230147
TI  - Identification of severe or extensive coronary artery disease in women by
      adenosine technetium-99m sestamibi SPECT.
AB  - To assess the ability of adenosine technetium-99m sestamibi myocardial perfusion
      single-photon emission computed tomography (SPECT) to identify high-risk women
      with severe or extensive coronary artery disease (CAD), we studied 130
      consecutive women who underwent adenosine sestamibi myocardial perfusion SPECT
      and catheterization within 2 months. Severe (> or = 50% stenosis of left main
      coronary artery, > or = 90% stenosis in the proximal left anterior descending or
      in > or = 2 coronary arteries) or extensive (> or = 70% stenosis in 3 vessels)
      CAD was present in 54 patients, whereas 76 had no CAD or mild to moderate CAD.
      Semiquantitative visual SPECT analysis used 20 segments and a 5-point scoring
      system (0 = normal, 4 = absent uptake). Among the clinical, hemodynamic and
      nuclear variables analyzed, univariate predictors of severe or extensive CAD
      included a higher prescan likelihood of CAD, history of myocardial infarction, a
      higher heart rate at rest, a lower increase in heart rate during adenosine
      infusion, a higher summed stress score, summed reversibility score, and
      multivessel scan abnormality. Multivariate logistic analysis of the most
      predictive clinical (prescan likelihood of CAD), hemodynamic (increase in heart
      rate during adenosine infusion), and scan variables (summed stress score)
      revealed summed stress score (chi-square = 32; p <0.0001) and prescan likelihood
      of CAD (chi-square = 6.4; p <0.05) as the only independent predictors of severe
      or extensive CAD. Based on these logistic models, we determined the probability
      for the presence of severe or extensive CAD in patients with low, intermediate,
      and high prescan likelihood of CAD across the range of values of a summed stress
      score. This revealed that there were incremental increases in the probability for
      severe or extensive CAD both as a function of prescan likelihood of CAD and
      summed stress score. A severely abnormal scan (summed stress score > 8) during
      adenosine technetium-99m sestamibi myocardial perfusion SPECT had a high
      sensitivity of 91% and a moderately high specificity of 70% for identifying high
      risk women with severe or extensive CAD. These results coupled with the
      previously defined prognostic significance of these findings suggest this test to
      be a useful diagnostic tool for the evaluation of CAD in women.

PMID- 9230148
TI  - Prognostic associations of Minnesota Code serial electrocardiographic change
      classification with coronary heart disease mortality in the Multiple Risk Factor
      Intervention Trial.
AB  - A central requirement for epidemiologic studies and clinical trials is a bias
      free, objective determination of cardiac incidence rates between comparison
      groups. Epidemiologic studies and clinical trials frequently use changes in the
      Minnesota Code to document incident ischemic events. An electrocardiographic
      (ECG) classification system was developed to document significant ECG pattern
      change using objective comparison rules for side-by-side annual ECG comparison.
      Previously, we showed that major evolving Q waves were strongly and independently
      associated with total and coronary disease mortality. Using baseline-to-annual
      ECG comparisons in the Multiple Risk Factor Intervention Trial, we evaluated
      major evolving Q waves, minor evolving Q waves combined with major evolving ST-T
      waves and major evolving ST-T waves alone for their prognostic associations with
      coronary, cardiovascular, and total mortality during 16 years of follow-up. The
      16-year coronary mortality rate in men with evolving minor Q waves plus evolving
      ST-T waves had an average adjusted relative risk of 4, equivalent to that of a
      major evolving Q wave. These risk ratios held whether a clinical infarction had
      occurred. Silent evolving ST-T waves without Q-wave change had an average
      adjusted relative coronary mortality risk of 1.6. Serial comparison methodology
      documents additional incident ischemic ECG events beyond the traditional major
      Minnesota Q-code change used in older epidemiologic studies. The procedure is
      standardized, quantitative, and repeatable. It is applicable for any study,
      present or past, that used Minnesota coding. The method is also well suited for
      incorporation in computer analysis programs.

PMID- 9230150
TI  - Hemorrhagic complications of intravenous heparin use.
AB  - To document the incidence of bleeding complications occurring in patients
      admitted to a cardiology service treated with intravenous heparin and to identify
      the major risk factors for these adverse events. Intravenous heparin is effective
      treatment for a variety of cardiologic conditions but is associated with a number
      of adverse effects, including hemorrhage. During the study, 1,253 consecutive
      patients were admitted for acute cardiac care and of these, 416 were treated with
      intravenous heparin. A total of 39 complications occurred in 37 heparin-treated
      patients (8.9%), of which 23 were hemorrhagic complications occurring in 21
      heparin-treated patients (5.5%). Of these hemorrhagic complications, 12 were
      directly related to a vascular access site and 11 were apparently "spontaneous"
      hemorrhages. There was no apparent relation between the dose (mean 1,021 U/hour
      [range 531 to 1,882]) or duration (6.7 +/- 5.7 days) of heparin therapy and
      hemorrhagic complications. In a multivariate analysis, female gender (odds ratio
      [OR] 4.76 [14.39 to 1.56]; p = 0.006), recent thrombolytic therapy (OR 12.9 [4.1
      to 40.6]; p <0.0001), and a reduced admission hemoglobin (OR 1.41 [0.52 to 0.97];
      p = 0.031) were significantly predictive of a hemorrhagic event. The incidence of
      cardiac catheterization procedures was not significantly higher in the
      complication group (OR 3.9 [0.84 to 18.4]; p = 0.082). Aspirin therapy, admission
      platelet count, and weight were noncontributory. Hemorrhagic complications
      occurred in 5.5% of patients receiving a continuous infusion of heparin. The use
      of thrombolytic therapy, female gender (independent of weight), and a reduced
      admission hemoglobin were significant independent predictors of hemorrhagic
      events.

PMID- 9230149
TI  - Plasma levels of tissue plasminogen activator and plasminogen activator inhibitor
      1 are correlated with the presence of transplant coronary artery disease in
      cardiac transplant recipients.
AB  - Hemostatic factors are involved in the pathogenesis of native coronary artery
      disease. However, their role in transplant coronary artery disease is less
      established. To assess the role of hemostatic factors in transplant coronary
      artery disease we studied 52 consecutive cardiac transplant patients. The
      presence of transplant coronary artery disease was determined by angiography.
      Plasma levels of tissue plasminogen activator (t-PA), plasminogen activator
      inhibitor-1 (PAI-1), von Willebrand Factor (vWF), and fibrin D-dimer were
      determined by enzyme-linked immunosorbent assays. Serum lipids were measured by
      enzymatic methods. Patients with transplant coronary artery disease had higher
      circulating t-PA (8.6 +/- 0.8 vs. 5.4 +/- 0.6 ng/ml, p = 0.021) and PAI-1 antigen
      concentrations (38.0 +/- 3.4 vs 25.8 +/- 2.2 ng/ml, p = 0.037). t-PA and PAI-1
      antigen concentrations correlated with the severity of angiographic disease (R =
      0.34; p = 0.014 for t-PA, and R = 0.45; p = 0.001 for PAI-1). Serum cholesterol
      levels were higher in patients with transplant coronary artery disease (221 +/-
      7.6 vs 191 +/- 9.2 mg/dl, p = 0.039). Serum triglycerides were also higher in
      patients with transplant coronary artery disease by angiography (246 +/- 38.3 vs
      139 +/- 20.8 mg/dl, p = 0.050). Multivariate analysis identified t-PA antigen (p
      = 0.003) and triglyceride levels (p = 0.038) as independent predictors for the
      presence of transplant coronary artery disease. We conclude that cardiac
      transplant patients with evidence of transplant coronary artery disease on
      coronary angiography have altered hemostatic function which is reflected by
      elevated levels of circulating t-PA and PAI-1 antigens. The interaction of the
      hemostatic system and serum lipids in the development of transplant coronary
      artery disease warrants further study.

PMID- 9230151
TI  - Safety of slow pathway ablation in patients with atrioventricular node reentrant
      tachycardia and a long fast pathway effective refractory period.
AB  - Radiofrequency catheter ablation is an accepted primary therapy for
      atrioventricular (AV) node reentrant tachycardia (AVNRT). There is concern that
      slow pathway ablation in patients with a long anterograde fast pathway effective
      refractory period (ERP) may potentially impair subsequent node conduction.
      Eighteen patients (14 women; age 53 +/- 20 years) with symptomatic AVNRT, whose
      fast pathway ERP at baseline was > or = 500 ms, underwent slow pathway ablation.
      Their outcome was compared with 24 consecutive control patients (17 women; age 42
      +/- 17 years) who underwent ablation for AVNRT whose fast pathway ERP at baseline
      was <500 ms (controls). Slow pathway ablation was successful in 16 patients
      (90%). One patient had inadvertent fast pathway ablation. In a second patient the
      slow pathway could not be ablated because of recurrent transient AV block.
      Ablation was successful in all patients in the control group. Transient AV block
      related to current application occurred in 4 patients (22%) versus 1 control (4%)
      (p = 0.07). After ablation, the AV node refractory period increased in patients
      (368 +/- 68 to 428 +/- 92 ms, p = 0.02) and in controls (282 +/- 35 to 336 +/- 55
      ms, p <0.0001), but the fast pathway ERP shortened in both groups (patients: 558
      +/- 63 to 428 +/- 92 ms, p = 0.003; controls: 356 +/- 53 to 336 +/- 55 ms, p =
      0.05). Furthermore, the slope of the regression line relating to shortening of
      the fast pathway ERP to the baseline ERP was markedly steeper in patients
      compared with controls (1.9 vs 0.4, p <0.0001). The shortening of the fast
      pathway ERP was greater in patients compared with controls (122 +/- 130 vs 21 +/-
      50 ms, p = 0.001). During a mean follow-up of 18 +/- 11 months, 1 patient with
      severe coronary artery disease died suddenly 2 years after ablation. There was no
      recurrence of clinical tachycardia, and none of the patients developed symptoms
      of bradycardia or required permanent pacing. Thus, slow pathway ablation in
      patients with AVNRT and a long fast pathway ERP is safe and effective.

PMID- 9230153
TI  - Usefulness of microalbuminuria in predicting cardiovascular mortality in treated
      hypertensive men with and without diabetes mellitus. Risk Factor Intervention
      Study Group.
AB  - In the present study we report on the predictive power of microalbuminuria for
      total and cardiovascular mortality in a prospective study (mean follow up 6.3
      years) of treated hypertensive men, aged 50 to 72 years, with (n = 94) and
      without (n = 345) maturity onset diabetes mellitus. Thirty-three (35.1%) of the
      hypertensive patients with diabetes mellitus died during the follow-up period
      compared with 57 patients (16.5%) in the hypertensive group without diabetes
      mellitus (p <0.0002). In those with diabetes mellitus and hypertension, a log
      rank test revealed a lower cardiovascular mortality in the normoalbuminuric group
      compared with both the microalbuminuric (p = 0.035) and the macroalbuminuric
      group (p = 0.002). The logarithm of urinary albumin excretion was a predictor of
      both total (p = 0.009) and cardiovascular (p = 0.001) mortality during the follow
      up period using Cox regression analysis. This relation remained significant even
      after adjustment for other risk factors. HbA1c was also an independent predictor
      of total and cardiovascular mortality. In patients without diabetes mellitus, the
      small group of patients with macroalbuminuria had a markedly increased
      cardiovascular mortality compared with both the microalbuminuric (p <0.0001) and
      the normoalbuminuric groups (p <0.0001). No difference was observed between the
      normoalbuminuric and the microalbuminuric groups. Smoking at entry and
      concomitant cardiovascular disease at entry were independent predictors of
      cardiovascular mortality in these patients. We conclude that microalbuminuria was
      an independent predictor for cardiovascular mortality in treated hypertensive men
      with maturity onset diabetes mellitus. Macroalbuminuria, but not
      microalbuminuria, predicted cardiovascular mortality in nondiabetic treated
      hypertensive men.

PMID- 9230152
TI  - QRS prolongation is associated with inducible ventricular tachycardia after
      repair of tetralogy of Fallot.
AB  - Prolonged QRS duration on the electrocardiogram has been found to predict adverse
      arrhythmic events in patients late after repair of tetralogy of Fallot. Whether
      QRS duration can also predict inducible ventricular tachycardia (VT) at
      electrophysiologic study is unknown. Between 1984 and 1995 we studied 135
      survivors of tetralogy of Fallot surgery whose age at surgery was 34 days to 37
      years (3.7 +/- 3.9, median 2.5) and age at electrophysiologic study was 1.4 to 43
      years (9.7 +/- 8.2, median 6.7). QRS duration was 80 to 240 ms (137 +/- 29) and >
      or = 180 ms in 9 patients. Sustained VT was induced in 22 patients (monomorphic
      in 17). Induced sustained monomorphic VT was related to QRS duration, right
      ventricular dimension, H-V interval, and presence of symptoms. QRS duration was
      also related to induced sustained monomorphic VT by multivariate analysis. QRS
      duration > or = 180 ms was 35% sensitive and 97% specific for induced sustained
      monomorphic VT. QRS duration was related to induced sustained monomorphic VT even
      when only asymptomatic patients were analyzed. A QRS duration > or = 180 ms was
      100% sensitive and 96% specific for detecting clinical VT. Prolonged QRS duration
      on the electrocardiogram is associated with induced sustained monomorphic VT on
      electrophysiologic study. The finding of prolonged QRS duration should suggest
      the need for further testing to determine the risk of adverse arrhythmic events
      in patients after repair of tetralogy of Fallot, even if they are asymptomatic.

PMID- 9230154
TI  - Survival and risk factor analysis for the Norwood procedure for hypoplastic left
      heart syndrome.
AB  - The optimal approach to hypoplastic left heart syndrome (HLHS) is controversial.
      The palliative Norwood operation, cardiac transplantation, and no surgical
      intervention have all been advocated. Centers that perform the Norwood operation
      have met with varied results, and conflicting reports exist regarding factors
      predictive of stage I outcome. From January 1990 to January 1996, 67 patients
      with HLHS were admitted with intent to perform the staged Norwood procedure.
      Fourteen patients did not undergo surgery. In the 53 patients treated surgically,
      outcome was reviewed, and 10 potential risk factors for first stage mortality
      were analyzed. Forty-one infants survived the Norwood I operation to hospital
      discharge (77% of the surgically treated patients and 61% of the entire group,
      including those who did not undergo operation) with 6 additional deaths 3 to 5
      months after operation. Univariate analysis showed cardiopulmonary bypass time
      and circulatory arrest time to be significant risk factors for hospital
      mortality. Multivariate analysis revealed only cardiopulmonary bypass time as
      significant (p <0.01). Of the 15 prenatally diagnosed newborns who underwent
      surgery, 11 survived (p = 0.72). Ten of 11 patients with preoperative organ
      damage survived (p = 0.42). Among the 35 bidirectional Glenn (Norwood II) and
      Fontan (Norwood III) procedures performed, there were 2 deaths. The 5-year
      actuarial survival for patients who underwent operations was 61%. The Norwood
      procedure is a favorable option for the infant with HLHS. Surgical survival may
      be affected by a prolonged cardiopulmonary bypass time, but is not affected by
      other factors analyzed, including prenatal diagnosis and preoperative organ
      damage.

PMID- 9230155
TI  - Absent right superior vena cava in visceroatrial situs solitus.
AB  - Absence of the right superior vena cava (SVC) in visceroatrial situs solitus is
      rare (0.07% to 0.13% of congenital cardiovascular malformations), and little is
      known about the type and frequency of additional heart defects and arrhythmias.
      We reviewed previous publications and present 9 new cases. Based on 121 known
      cases, we found that this anomaly is typically characterized by: (1) persistence
      of the left SVC draining into the right atrium by way of the coronary sinus, and
      (2) left-sided azygos vein draining into the left SVC. Less constant features
      were: (3) additional cardiovascular malformations (46%), and (4) rhythm
      abnormalities (36%) that usually appeared related to the complications of old
      age. Since absence of the right SVC is clinically silent, its status should be
      assessed echocardiographically prior to invasive medical or surgical procedures.
      This is important to avoid various management difficulties during the following
      procedures: (1) implantation of a transvenous pacemaker, (2) placement of a
      pulmonary artery catheter for intraoperative or intensive care unit monitoring
      without fluoroscopy, (3) systemic venous cannulation for extracorporeal membrane
      oxygenation, (4) systemic venous cannulation for cardiopulmonary bypass, (5)
      partial or total cavopulmonary anastomoses; and (6) orthotopic heart
      transplantation and endomyocardial biopsies.

PMID- 9230156
TI  - Relation of duration of symptoms with response to thrombolytic therapy in
      pulmonary embolism.
AB  - Five previous trials of pulmonary embolism (PE) thrombolysis showed individually
      that duration of symptoms did not affect lung scan reperfusion or angiographic
      clot lysis. We conducted an overview of 308 patients from these trials. Using 262
      pairs of pre- and postlysis lung scans and 222 pairs of angiograms, we evaluated
      the relation between duration of PE symptoms and changes in reperfusion and/or
      clot lysis following thrombolysis. When comparing baseline and 24-hour post
      thrombolysis lung scans, 77% of patients overall demonstrated improvement,
      including 69% who were treated 6 to 14 days after onset of symptoms. We detected
      an inverse relation between duration of symptoms and improvement on post
      treatment lung scan reperfusion scores. For each additional day of symptoms
      before PE thrombolysis, there was a decrement of 0.8% of lung tissue reperfusion
      on lung scanning (95% confidence interval [CI], 0.2% to 1.4%, p = 0.008).
      Adjustment for age and baseline lung scan defect had little effect on the results
      Similarly, on angiography, less clot lysis immediately following thrombolysis was
      observed in the group of patients with the longest duration of symptoms compared
      with those with the shortest symptom duration (mean = 1.0 score unit of
      angiographic improvement in those with symptoms for > or = 6 days vs 1.7 score
      units for < or = 1 day of symptoms, p = 0.03). This inverse relation between
      duration of symptoms and response to thrombolysis indicates that thrombolytic
      treatment should commence as soon as possible after PE is diagnosed. However,
      thrombolysis is still useful in patients who have had symptoms for 6 to 14 days.

PMID- 9230157
TI  - Effect of aspirin dosage and enteric coating on platelet reactivity.
AB  - Although aspirin is effective in the prevention and treatment of cardiovascular
      diseases, the optimal dose remains uncertain. The purpose of this study was to
      compare the platelet inhibitory and prostacyclin-sparing effects of 2 doses (81
      and 325 mg) and forms (enteric-coated and regular) of aspirin. Since platelet
      reactivity has been reported to increase after strenuous exercise, a known
      trigger of myocardial infarction, subjects were studied following maximal
      treadmill exercise as well as at rest. Forty male healthy subjects were evaluated
      using a randomized, double-blind, parallel study design. Blood samples were
      obtained before and after maximal treadmill exercise at baseline and after 7 days
      on aspirin therapy. Both enteric and regular aspirin in 81- and 325-mg dosages
      markedly inhibited adenosine diphosphate and epinephrine-induced aggregation at
      rest and after exercise. Aspirin also inhibited the platelet response to collagen
      as assessed by a longer lag time to aggregation. The prolongation of lag time was
      greater for 325 mg than for 81 mg (100 +/- 7 vs 91 +/- 7; p = 0.04, after
      exercise). There were no significant dose-related differences in plasma 6-keto
      prostaglandin F1alpha level; however, enteric-coated aspirin inhibited the
      exercise-induced increase in 6-keto-prostaglandin F1alpha to a lesser extent than
      regular aspirin. Although both doses (81 and 325 mg) and types (regular and
      enteric-coated) of aspirin inhibited adenosine diphosphate and epinephrine
      induced aggregation equally, the 325-mg dose inhibited collagen-induced
      aggregation to a greater extent than 81 mg. The greater platelet inhibition
      observed with 325 mg may be clinically relevant in acute coronary syndromes
      characterized by plaque rupture with extensive collagen exposure and platelet
      activation.

PMID- 9230158
TI  - The AVID trial: evidence based or randomized control trials--is the AVID study
      too late? Antiarrhythmics Versus Implantable Defibrillators.
AB  - A great body of clinical evidence has been accumulated--before and without the
      AVID trial--showing that implantable defibrillators prolong life better than
      currently available antiarrhythmic drugs. With this evidence already available,
      we question the validity of a trial that attempted, in effect, to place a price
      tag on life and quality of life.

PMID- 9230159
TI  - Prognostic significance of angina pectoris > or = 30 days before acute myocardial
      infarction in patients > or = 75 years of age.
AB  - We compared the prognostic significance of prior angina pectoris in 151 patients
      > or = 75 years of age admitted for acute myocardial infarction. There was a
      similar in-hospital course, but the long-term outcome was poorer in patients with
      prior angina.

PMID- 9230160
TI  - Intravascular therapeutic ultrasound thrombolysis in acute myocardial
      infarctions.
AB  - Catheter-delivered, therapeutic ultrasound was shown to effectively dissolve
      thrombus in vitro and in vivo. This first study in 14 patients with acute
      myocardial infarctions demonstrates that it is a safe and effective treatment
      alternative that deserves further clinical evaluation.

PMID- 9230161
TI  - Papillary muscle fractional shortening is a determinant of heart shape in
      patients with prior myocardial infarction.
AB  - To examine the relation between papillary muscle fractional shortening and heart
      shape, we performed quantitative echocardiography in 20 patients with prior
      myocardial infarction and 20 normal control subjects. Papillary muscle fractional
      shortening was markedly depressed in infarction patients and there was a high
      degree of correlation between papillary muscle fractional shortening and left
      ventricular shape, which was evident over a wide range of ejection fraction and
      shape.

PMID- 9230163
TI  - Community practice of primary angioplasty for myocardial infarction.
AB  - Results obtained with primary angioplasty at the community level do not duplicate
      the results of the published trials. Major changes in current community practice
      patterns are needed to achieve the success rates of the published trials.

PMID- 9230162
TI  - Effect of propranolol versus no propranolol on total mortality plus nonfatal
      myocardial infarction in older patients with prior myocardial infarction,
      congestive heart failure, and left ventricular ejection fraction > or = 40%
      treated with diuretics plus angiotensin-converting enzyme inhibitors.
AB  - At 32-month follow-up of older patients with prior myocardial infarction,
      congestive heart failure, and a left ventricular ejection fraction > or = 40%
      treated with diuretics plus angiotensin-converting enzyme inhibitors, and also
      with digoxin if atrial fibrillation was present, propranolol caused a 35%
      significant reduction in total mortality and a 37% significant decrease in total
      mortality plus nonfatal myocardial infarction compared with no propranolol. At 1
      year follow-up, propranolol caused a significantly greater increase in left
      ventricular ejection fraction (6%) and a significantly greater reduction in left
      ventricular mass (34 g) than did no propranolol (2% and 20 g, respectively).

PMID- 9230164
TI  - Response of symptomatic myocardial ischemia in ischemic cardiomyopathy to
      intensive vasodilator therapy.
AB  - To determine the cardiovascular protective effects of angiotensin-converting
      enzyme inhibitors, we examined the response to intensive vasodilator therapy in
      patients with ischemic cardiomyopathy and ongoing angina pectoris. We found that
      for patients with ischemic cardiomyopathy and ongoing active angina, intensive
      vasodilator therapy with angiotensin-converting enzyme inhibition and nitrates
      improved not only heart failure-related symptoms, but also resulted in a
      significant improvement in symptomatic ischemia and ischemia-related morbid
      events.

PMID- 9230165
TI  - Circadian release of serotonin across the coronary bed in patients with
      endothelial dysfunction.
AB  - Transcardiac serotonin differences in nonischemic patients with endothelial
      dysfunction significantly increased in the early morning. Platelet secretion
      could occur without coronary stenosis.

PMID- 9230166
TI  - Activated factor VII levels in patients with angiographically confirmed coronary
      artery disease.
AB  - We have examined factor VIIa levels in consecutive consenting patients undergoing
      coronary angiography (n = 702) to determine if levels are related to the presence
      of coronary arterial narrowing and to the degree and extent of that narrowing.
      Both men and women with clinically defined coronary artery disease (> or = 50%
      stenosis in at least 1 vessel) had factor VIIa levels that were similar to men
      and women with less stenosis or normal coronary arteries.

PMID- 9230167
TI  - Risk factors for the development of slow flow during rotational coronary
      atherectomy.
AB  - We investigated the clinical and angiographic risk profile of slow flow during
      rotational atherectomy. Lesion length, angina at rest, and use of beta blockers
      correlated independently with slow flow in the univariate as well as in the
      multivariate analysis.

PMID- 9230168
TI  - Femoral complications and bed rest duration after coronary arteriography.
AB  - This randomized study using a pneumatic compression device found no significant
      difference in the femoral complication rate between 4 and 6 hours of bed rest
      after Judkin's coronary arteriography. The positive implications for the
      organization of an efficient service in busy tertiary centers include reduced
      patient discomfort, earlier ambulation and discharge, efficient staff deployment,
      and enhanced throughput.

PMID- 9230169
TI  - Management of cardiac allograft vasculopathy by transmyocardial laser
      revascularization.
AB  - Transmyocardial laser revascularization provides a unique and effective
      intervention for symptomatic relief and improvement of myocardial perfusion in
      diffuse cardiac allograft vasculopathy.

PMID- 9230170
TI  - Failure of single- and multisite high-frequency atrial pacing to terminate atrial
      fibrillation.
AB  - This study determined the efficacy of single- and multisite atrial pacing for
      terminating episodes of atrial fibrillation induced in patients in the
      electrophysiology laboratory. One- to 5-second bursts of atrial pacing at a cycle
      length of 20 ms were not effective in terminating atrial fibrillation, when
      delivered either in the high right atrium or when delivered simultaneously at the
      high right atrium, midseptum, and coronary sinus.

PMID- 9230171
TI  - Negative lead I P waves during anteroseptal accessory pathway orthodromic
      reciprocating tachycardia.
AB  - Although a negative retrograde P wave in lead I during orthodromic reciprocating
      tachycardia is thought to indicate a left free wall accessory pathway, we
      describe similar negative P waves in lead I during orthodromic reciprocating
      tachycardia through anteroseptally situated accessory pathways.

PMID- 9230172
TI  - Predictors of fracture in the Accufix Atrial "J" lead.
AB  - The Accufix atrial lead has a "J"-shaped retention wire at the distal end that
      has been reported to fracture. Our findings suggest that the more deformed the J,
      the higher the incidence of fracture.

PMID- 9230173
TI  - Anatomy of atrioventricular nodal reentry investigated by intracardiac
      echocardiography.
AB  - Intracardiac echocardiography was used to evaluate posteroseptal space anatomy in
      patients with atrioventricular nodal reentrant tachycardia compared with patients
      with other mechanisms of tachycardia. The posteroseptal space was found to be
      significantly wider in patients with atrioventricular nodal reentry, suggesting
      an anatomic basis for dual atrioventricular nodal physiology.

PMID- 9230174
TI  - Predictors of natural killer cell-mediated cytotoxicity deficiency in advanced
      heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.
AB  - The effect of psychologic variables (situational emotional state and psychiatric
      diagnosis) and physiologic variables (plasma norepinephrine, decreased cardiac
      exercise capacity, and elevated pulmonary capillary wedge pressure) on natural
      killer cell activity was evaluated in 19 patients with advanced heart failure of
      ischemic or idiopathic origin. Only peak exercise capacity was independently
      predictive of natural killer cell deficiency.

PMID- 9230175
TI  - Effect of inadequate cardiac output reserve on exercise tolerance in patients
      with moderate mitral stenosis.
AB  - Twenty-nine patients with moderate mitral stenosis and 29 age-matched normal
      controls underwent symptom-limited upright bicycle exercise testing with
      simultaneous hemodynamic monitoring. Exercise tolerance in the mitral stenosis
      group was found to be limited by inadequate cardiac output reserve and not by
      resting mitral valve area or exercise pulmonary capillary wedge pressure.

PMID- 9230176
TI  - Late (five to nine years) follow-up after balloon dilation of valvular pulmonary
      stenosis in adults.
AB  - The transvalvular gradient was investigated in 14 patients with pulmonary
      stenosis 5 to 9 years after balloon valvuloplasty. None of the patients had
      developed restenosis, and in those who had a peak gradient >100 mm Hg before
      valvuloplasty, the gradient decreased further due to resolution of subvalvular
      muscular hypertrophy within 3 months after intervention.

PMID- 9230177
TI  - Effect of multiple coil closure of patent ductus arteriosus on blood flow to the
      left lung as determined by lung perfusion scans.
AB  - Lung perfusion scans reveal that multiple-coil closure of the ductus does not
      interfere with pulmonary blood flow. However, caution is necessary when placing
      multiple coils in small infants.

PMID- 9230178
TI  - Ischemic chest pain and global T-wave inversion in women with normal coronary
      angiograms.
AB  - Patients presenting with ischemic chest pain and electrocardiographic evidence of
      global T-wave inversion are most frequently women with intact left ventricular
      function and no critical stenosis of major coronary vessels. Hence, this syndrome
      has a good immediate and long-term prognosis.

PMID- 9230179
TI  - Relation of direct assessment of cardiac autonomic function with
      metaiodobenzylguanidine imaging to heart rate variability in diabetes mellitus.
AB  - Myocardial metaiodobenzylguanidine uptake predicts autonomic function in patients
      with diabetes mellitus and is significantly related to indexes reflecting
      sympathetic neural modulation of heart rate variability.

PMID- 9230180
TI  - A unique heart disease associated with a unique cancer: carcinoid heart disease.

PMID- 9230181
TI  - Filament disassembly and loss of mammary myoepithelial cells after exposure to
      lambda-carrageenan.
AB  - Carrageenans are naturally occurring sulfated polysaccharides, widely used in
      commercial food preparation to improve the texture of processed foods. Because of
      their ubiquity in the diet and their observed preneoplastic effects in intestinal
      cells, their impact on human mammary myoepithelial cells in tissue culture was
      studied. At concentrations as low as 0.00014%, lambda-carrageenan was associated
      with disassembly of filaments with reduced immunostaining for vimentin, alpha
      smooth muscle-specific actin, and gelsolin; increased staining for cytokeratin
      14; and cell death. The absence of mammary myoepithelial cells is associated with
      invasive mammary malignancy; hence, the destruction of these cells in tissue
      culture by a low concentration of a widely used food additive suggests a dietary
      mechanism for mammary carcinogenesis not considered previously.

PMID- 9230182
TI  - Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear
      cell carcinoma of the kidney.
AB  - The MN/CA9 protein is a tumor-associated antigen that has been shown to have
      diagnostic utility in identifying cervical dysplasia and carcinoma. MN/CA9
      expression is limited to very few normal tissues. We have now extended those
      observations to further investigate expression of the MN/CA9 protein in
      histological sections and fine-needle aspiration biopsy smears of normal kidney,
      benign renal cell lesions, all categories of renal cell carcinomas
      (clear/granular/spindle cell, chromophilic cell, chromophobic cell, and
      collecting duct cell RCCs), metastatic RCCs, and non-renal cell clear cell
      adenocarcinomas. We have found that high levels of MN/CA9 expression is seen in
      all primary RCCs, cystic RCCs, and metastatic RCCs, with the exception of two
      cases of the chromophobe cell type, which were MN/CA9 negative. Identical MN/CA9
      immunostaining was also observed in the aspiration cytological smears. In
      contrast, all benign lesions, including pyelonephritis, renal cysts, adenomas,
      oncocytomas, and normal kidney, did not express the MN/CA9 protein. Thus, we
      conclude that MN/CA9 protein expression could serve as a valuable adjunct to the
      cytological and histological diagnosis of benign renal cysts versus cystic RCC,
      adenoma versus RCC, and oncocytoma versus granular cell RCC. Diffuse membraneous
      staining of all RCCs (with the exception of chromophobic cell RCC) suggests that
      MN/CA9 protein expression might have an important clinical utility in the early
      detection and treatment of RCC. Absence of MN/CA9 expression in non-renal cell
      clear cell adenocarcinoma also indicates that MN/CA9 protein expression may be
      used as a differential diagnostic biomarker of metastatic clear cell RCC.

PMID- 9230183
TI  - Butylated hydroxytoluene exposure is necessary to induce lung tumors in BALB mice
      treated with 3-methylcholanthrene.
AB  - Chronic butylated hydroxytoluene (BHT) treatment after a single administration of
      a carcinogen increases lung tumor multiplicity in some inbred strains of mice. We
      report that BALB/cOla and BALB/cByJ mice given a low dose (10 microg/g of body
      weight) of 3-methylcholanthrene (MCA) develop no lung tumors unless this is
      followed by chronic BHT exposure. Slightly higher MCA doses (15 and 25 microg/g)
      induce low lung tumor multiplicities (0.6 and 1.9 tumors/mouse, respectively)
      that are increased 12-26-fold by chronic BHT administration. This low-dose
      MCA/BHT model in BALB mice will facilitate the identification of genes regulating
      susceptibility to lung tumor promotion and pulmonary chemopreventative agents
      that act at a postinitiation site.

PMID- 9230184
TI  - Aryl hydrocarbon receptor knockout mice (AHR-/-) exhibit liver retinoid
      accumulation and reduced retinoic acid metabolism.
AB  - Livers from aryl hydrocarbon receptor-null mice showed a 3-fold increase in
      retinoids and a 65% decrease in retinoic acid metabolism. Levels of expression of
      the retinoic acid 4-hydroxylase, P450RAI, did not change, whereas cytochrome
      P4501A2 levels were lower in the null mouse, as shown earlier; however, this
      enzyme was found not to be active toward retinoic acid. These data suggest that
      aryl hydrocarbon receptor controls retinoic acid catabolism, through modulation
      of an unidentified target gene. Aldehyde dehydrogenases 1 and 2 were down
      regulated markedly in the aryl hydrocarbon receptor-deficient mouse liver.
      2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P4501A2 but not the
      aldehyde dehydrogenases in wild-type mice, suggesting that aryl hydrocarbon
      receptor is not involved directly in the down-regulation of this gene.
      Transglutaminase II, a retinoic acid-responsive gene product, was increased 2
      fold, consistent with the liver fibrosis phenotype observed in the null mice.
      These findings suggest a molecular connection between xenobiotic-activated
      receptor signaling and retinoid homeostasis.

PMID- 9230185
TI  - Benzene poisoning, a risk factor for hematological malignancy, is associated with
      the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone.
AB  - Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary
      in their response to this toxic agent. To evaluate the impact of interindividual
      variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1)
      benzene and its metabolites, we carried out a case-control study in Shanghai,
      China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we
      show is itself strongly associated with subsequent development of acute
      nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk,
      70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were
      determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the
      fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50
      controls. Subjects with both a rapid fe(6-OH). and two copies of the NQO1 609C-
      >T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of
      BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type
      NQO1 alleles. In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP
      risk. This is the first report that provides evidence of human susceptibility to
      benzene-related disease. Further evaluation of susceptibility for hematotoxicity
      and hematological malignancy among workers with a history of occupational
      exposure to benzene is warranted.

PMID- 9230186
TI  - Calorie restriction induces a p53-independent delay of spontaneous carcinogenesis
      in p53-deficient and wild-type mice.
AB  - We reported previously that calorie restriction (CR) delays spontaneous
      carcinogenesis in p53-deficient (p53-/-) mice, suggesting that CR modulates
      carcinogenesis by p53-independent mechanisms. To further evaluate the role of
      p53, we monitored tumor development in p53-/- and wild-type (p53+/+) mice fed ad
      libitum (AL) or a CR regimen (60% of AL calorie intake). CR delayed tumor
      mortality in p53-/- and p53+/+ mice (mean time to death, 169 and 648 days,
      respectively) relative to AL feeding (104 and 470 days). The estimated age
      specific cancer death rate AL:CR ratios were 4.3 for p53-/- mice and 4.4 for
      p53+/+ mice. Thus, despite the accelerated onset of carcinogenesis in p53-/-
      mice, the tumor-delaying effect of CR was similar in the two genotypes.

PMID- 9230187
TI  - Heat inactivation of Ku autoantigen: possible role in hyperthermic
      radiosensitization.
AB  - Heat shock prior, during, or immediately after ionizing radiation synergistically
      increases cell killing, a phenomenon termed hyperthermic radiosensitization.
      Recently, we have shown a constitutive DNA-binding factor in rodent cells that is
      inactivated by heat shock to be identical to Ku autoantigen. Ku, consisting of an
      Mr 70,000 (Ku70) and an Mr 86,000 (Ku80) subunit, is a heterodimeric nuclear
      protein and is the DNA-binding regulatory component of the mammalian DNA
      dependent protein kinase DNA-PK. Recent genetic and biochemical studies indicate
      the involvement of Ku and DNA-PK in DNA double-strand break repair and V(D)J
      recombination. On the basis of these findings, we propose that heat-induced loss
      of the DNA-binding activity of Ku may lead to hyperthermic radiosensitization. To
      test this hypothesis, we examined and compared the DNA-binding activity of Ku,
      the DNA-PK kinase activity, and hyperthermic radiosensitization in rodent cells
      immediately after heat shock and during post-heat shock recovery at 37 degrees C.
      Our results show that the heat-induced loss of Ku-DNA binding activity correlates
      well with an increased radiosensitivity of the heat-shocked cells, and
      furthermore, the loss of synergistic interaction between heat and radiation
      parallels the recovery of the DNA-binding activity of Ku. On the other hand, the
      heat-induced decrease of DNA-PK activity did not correlate with hyperthermic
      radiosensitization. Our data, for the first time, provide evidence for a role of
      Ku protein in modulating the cellular response to combined treatments of heat
      shock and ionizing radiation.

PMID- 9230188
TI  - Cyclin-dependent kinase 6 is the principal target of p27/Kip1 regulation of the
      G1-phase traverse in 1,25-dihydroxyvitamin D3-treated HL60 cells.
AB  - Control of cell proliferation remains of intense interest in cancer research. In
      the 1,25-dihydroxyvitamin D3 HL60 cell system, G1 arrest has been shown to be
      mediated by elevated levels of p27/Kip1 protein. We show here that the main
      target of the elevated p27/Kip1 in this system is cyclin-dependent kinase (Cdk)
      6. The activity of Cdk2 is also down-regulated, and this is associated with
      altered and reduced levels of cyclin E in the kinase complex. Paradoxically, the
      kinase activity of Cdk4 is elevated, in spite of an almost complete G1 block.
      These data show that the functions of Cdk4 and Cdk6 are not redundant and that
      Cdk6 and Cdk2 activities are regulated by 1,25-dihydroxyvitamin D3.

PMID- 9230189
TI  - Expression of transforming growth factor beta type II receptor reduces
      tumorigenicity in human gastric cancer cells.
AB  - Expression of transforming growth factor beta (TGF-beta) receptor type II (RII)
      is required for the growth-inhibitory effects of TGF-beta on proliferating
      epithelial cells. TGF-beta RII mutations have been identified in a broad spectrum
      of human epithelial malignancies, including colon and gastric cancers, and are
      highly correlated with development of TGF-beta resistance in cell lines derived
      from these tumors. In this study, the role of TGF-beta RII in regulating the
      tumorigenic potential of the SNU-638 human gastric cancer cell line was
      investigated by infecting these cells with retroviral construct (MFG) expressing
      TGF-beta RII. The SNU-638 cell line displays the DNA replication error phenotype
      and encodes a truncated, inactive TGF-beta RII protein. Infection of these cells
      with retroviral constructs expressing wild-type TGF-beta RII led to significant
      increases in TGF-beta RII mRNA and protein expression. These cells responded to
      exogenous TGF-beta with reduced proliferation compared to that of control cells
      infected with retroviral vector expressing chloramphenicol acetyltranferase.
      Addition of TGF-beta-neutralizing antibodies led to increased proliferation of
      wild-type TGF-beta RII-expressing SNU-638 cells but had no effect on control
      cells. The latter finding suggests that TGF-beta acts in an autocrine fashion to
      inhibit cell proliferation in SNU-638 cells. When transplanted into athymic nude
      mice, wild-type TGF-beta RII-expressing SNU-638 cells showed decreased and
      delayed tumorigenicity compared with control cells. This study suggests a strong
      association between the expression of wild-type TGF-beta RII and the degree of
      malignancy in human gastric cancer cells.

PMID- 9230190
TI  - Marked genetic differences between stage pTa and stage pT1 papillary bladder
      cancer detected by comparative genomic hybridization.
AB  - Little is known about the genetic changes underlying invasive tumor growth in
      bladder cancer. Because alterations that are linked to invasive tumor growth may
      be detectable in minimally invasive (stage pT1) but not in noninvasive (stage
      pTa) tumors, we searched for genetic differences between 28 pTa and 28 papillary
      pT1 bladder tumors by comparative genomic hybridization. Losses of 9q (54%), 9p
      (39%), and Y (28%) and gains of 1q (14%) were most prevalent in pTa tumors. These
      changes may play a role in the initiation of noninvasive papillary bladder
      cancer. The total number of aberrations was higher in pT1 tumors (6.5 +/- 5.4)
      than in pTa tumors (2.3 +/- 2.1; P = 0.0003), suggesting an increased genetic
      instability at stage pT1. Specific alterations, which were significantly more
      frequent in pT1 than in pTa tumors (P < or = 0.05), included deletions at 2q (36%
      of pT1 tumors), 8p (32%), and 11p (21%) and gains at 1q (54%), 8q (32%), 3p, 3q,
      5p, 6p, and 10p (18% each). These loci are candidates for carrying genes involved
      in invasive tumor growth in bladder cancer. High-level amplifications at 1q22-24,
      3p24-25, 6p22, 8p12, 8q21-22, 10p12.1-14, 11q13, 12q15-21, 13q31-33, Xp11-13, and
      Xq21-22.2 may pinpoint the location of oncogenes with relevance for bladder
      cancer.

PMID- 9230191
TI  - Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant
      adenovirus-transduced murine dendritic cells.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that process and
      present antigenic peptides and are capable of generating potent T-cell immunity.
      A murine tumor model was developed to evaluate methods of genetic immunization to
      the human MART-1/Melan-A (MART-1) melanoma antigen. A poorly immunogenic murine
      fibrosarcoma line (NFSA) was stably transfected with the MART-1 gene. This
      transfected tumor [NFSA(MART1)] grows progressively in C3Hf/Kam/Sed (H-2k) mice.
      Partial protection against a challenge with NFSA(MART1) could be achieved with
      i.m. injections of a MART-1 expression plasmid or with systemic administration of
      an adenovirus vector expressing MART-1. However, superior protection was achieved
      when granulocyte macrophage colony-stimulating factor/interleukin-4
      differentiated murine DCs transduced with an adenovirus vector expressing MART-1
      were used for immunization. Both partial and complete protection could be
      achieved with i.v. administration of MART-1-engineered DCs. Splenocytes from
      immunized mice contained MHC class 1-restricted CTLs specific for MART-1. This
      preclinical model of genetic immunization supports a therapeutic strategy for
      human melanoma.

PMID- 9230192
TI  - Biological properties of Ret with cysteine mutations correlate with multiple
      endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and
      Hirschsprung's disease phenotype.
AB  - We investigated the transforming activity of the ret proto-oncogene with a
      mutation in cysteine 609, 611, 618, 620, 630, or 634 detected in patients with
      multiple endocrine neoplasia type 2A (MEN 2A), familial medullary thyroid
      carcinoma (FMTC), or Hirschsprung's disease. Of these cysteine mutations, codon
      634 mutations are known to be correlated with the development of MEN 2A, whereas
      codon 609, 618, or 620 mutations were detected in two-thirds of FMTCs and in
      several cases of Hirschsprung's disease. Analysis of a total of 18 mutant genes
      revealed that codon 634 mutations have the highest transforming activity. The
      activity of ret with a codon 609, 611, 618, or 620 mutation and with a codon 630
      mutation was approximately 3- to 5-fold and 2-fold lower than that of ret with a
      codon 634 mutation, respectively. In addition, different amino acid substitutions
      for the same cysteine displayed comparable transforming activity. The expression
      of the cell surface form of Ret with codon 609, 611, 618, or 620 mutation was
      very low compared with that of Ret with codon 634 mutation, indicating that the
      former four mutations might impair transport of Ret to the plasma membrane, as
      observed for several Hirschsprung mutations affecting the Ret extracellular
      domain. These results thus suggest that mutations in cysteine 609, 611, 618, or
      620 may have the potential to develop Hirschsprung's disease in addition to MEN
      2A and FMTC.

PMID- 9230193
TI  - Inositol hexaphosphate inhibits cell transformation and activator protein 1
      activation by targeting phosphatidylinositol-3' kinase.
AB  - Inositol hexaphosphate (InsP6) is the most abundant inositol phosphate found in
      plants. In mammalian cells, the concentrations of InsP6 are between 10 and 100
      microM. Previous work has indicated that InsP6 is an effective cancer
      chemopreventive and chemotherapeutic agent. However, the molecular mechanisms
      involved in the inhibition of carcinogenesis by InsP6 remain unclear. In this
      study, we investigated the influence of InsP6 on tumor promoter-induced cell
      transformation and signal transduction pathways leading to activator protein 1
      activation, which is considered to play a crucial role in tumor promotion. InsP6
      markedly blocks epidermal growth factor-induced phosphatidylinositol-3 (PI-3)
      kinase activity in a dose-dependent manner in JB6 cells and directly in vitro.
      Blocking PI-3 kinase activity by InsP6 profoundly impairs epidermal growth factor
      or phorbol ester-induced JB6 cell transformation and extracellular signal
      regulated protein kinases activation, as well as activator protein 1 activation.
      These results provide the first evidence that the molecular mechanism of InsP6
      antitumor promotion effect targets and blocks PI-3 kinase activation and
      demonstrate that PI-3 kinase can serve as a molecular target for the development
      of cancer chemopreventive agents.

PMID- 9230194
TI  - Infant acute leukemias show the same biased distribution of ALL1 gene breaks as
      topoisomerase II related secondary acute leukemias.
AB  - The ALL1 gene (also called MLL, HRX, or Htrx1) at the cytogenetic band 11q23 is
      consistently altered by chromosome rearrangements in acute leukemias (ALs) of
      early infancy, in ALs developed after exposure to topoisomerase (topo) II
      inhibitory drugs, and in a small subset of de novo ALs in children and adults.
      Because exposure to natural or medicinal substances blocking topo II during
      pregnancy have been proposed as etiological agents for infant leukemia, we have
      compared the distribution of ALL1 gene breakpoints in infant leukemias with an
      altered ALL1 gene configuration to those in secondary leukemia associated with
      prior exposure to topo II targeting drugs and in reference to the major topo
      consensus binding site in exon 9. ALL1 gene breakpoint distribution was
      determined by Southern blot hybridization and/or reverse transcription-PCR of the
      ALL1/AF4 fusion cDNA in 70 patients. Using restriction enzyme analysis, the 8.3
      kb ALL1 breakpoint cluster region was divided in a centromeric portion of 3.5 kb
      (region A) and telomeric portion of a 4.8 kb (region B). ALL1 breakpoint were
      located in region A in 8 of 28 (28.5%) cases of infant ALs, 16 of 24 (66%) cases
      of de novo ALs, and 0 of 5 cases of therapy-related (TR) ALs. Conversely, ALL1
      breakpoints in region B were detected in 20 of 28 (71.5%) cases of infant AL, 8
      of 24 (33%) cases of de novo AL, and 5 of 5 (100%) cases of TR AL (P = 0.002).
      These results were confirmed by direct sequencing of the ALL1/AF4 fusion
      transcript in 30 cases (19 infants and 11 child and adult de novo cases). The
      analysis of ALL1/AF4 junction types showed that children and adults with de novo
      leukemia had ALL1 breakpoints in intron 6 (9 cases) or intron 7 (2 cases),
      whereas breakpoints in infant cases were mainly located in intron 8 (14 cases)
      and less frequently in intron 6 (4 cases) and intron 7 (1 case). The difference
      in ALL1 breakpoint location between infant and noninfant AL patients with
      ALL1/AF4 fusion was statistically significant (P = 0.00005). These data
      demonstrated that infant and TR ALs share a similar biased clustering of ALL1
      gene breakpoints, which supports the possibility that topo II inhibitors may also
      operate in utero and play a crucial role in the etiology of infant leukemia.

PMID- 9230195
TI  - Hepsin, a cell surface serine protease identified in hepatoma cells, is
      overexpressed in ovarian cancer.
AB  - Extracellular proteases mediate the digestion of neighboring extracellular matrix
      components in initial tumor growth, allow shedding or desquamation of tumor cells
      into the surrounding environment, provide the basis for invasion of basement
      membranes in target metastatic organs, and are required for release and
      activation of many growth and angiogenic factors. We identified overexpression of
      the serine protease hepsin gene in ovarian carcinomas and investigated the
      expression of this gene in 44 ovarian tumors (12 low malignant potential tumors
      and 32 carcinomas) and 10 normal ovaries. Quantitative PCR was used to determine
      the relative expression of hepsin compared to that of beta-tubulin. The mRNA
      expression levels of hepsin were significantly elevated in 7 of 12 low malignant
      potential tumors and in 27 of 32 carcinomas. On Northern blot analysis, the
      hepsin transcript was abundant in carcinoma but was almost never expressed in
      normal adult tissue, including normal ovary. Our results suggest that hepsin is
      frequently overexpressed in ovarian tumors and therefore may be a candidate
      protease in the invasive process and growth capacity of ovarian tumor cells.

PMID- 9230196
TI  - Normal polymorphism in the incomplete trinucleotide repeat of the arginine-rich
      protein gene.
AB  - The arginine-rich protein (ARP) gene was recently cloned and localized to human
      chromosome band 3p21. Recent reports have suggested that ARP is mutated in a high
      percentage of different human tumors. We amplified and sequenced the multiple
      arginine coding area of the ARP gene in primary head and neck, non-small cell
      lung, and renal cell cancers. We found a high frequency of genetic changes in
      this region, including a single base pair substitution and deletions of arginine
      repeats in primary tumors. However, these changes were always present in matched
      normal controls. Thus, the variations in the ARP trinucleotide repeat region
      represent normal polymorphisms rather than tumor-specific mutations.

PMID- 9230197
TI  - Retinoids suppress epidermal growth factor-induced transcription of
      cyclooxygenase-2 in human oral squamous carcinoma cells.
AB  - Cyclooxygenase-2 (Cox-2), the inducible form of cyclooxygenase, is up-regulated
      in tumors and transformed cells. Because this enzyme catalyzes the formation of
      prostaglandins from arachidonic acid, chemopreventive strategies that suppress
      its expression could be useful for preventing cancer. We investigated whether
      retinoids suppressed basal expression of Cox-2 or EGF-mediated induction of Cox-2
      in human oral squamous carcinoma cells. Treatment with retinoids [all-trans
      retinoic acid (all-trans-RA), 9-cis-RA, 13-cis-RA, and retinyl acetate]
      suppressed both basal levels of Cox-2 and EGF-mediated induction of Cox-2 protein
      and synthesis of prostaglandin E2. Retinoids also suppressed the induction of Cox
      2 mRNA by EGF. Transient transfection experiments showed that EGF caused about a
      100% increase in Cox-2 promoter activity, an effect that was suppressed by
      retinoids. Levels of epidermal growth factor receptor were unaffected by
      retinoids. Epidermal growth factor caused a nearly 10-fold increase in mitogen
      activated protein kinase activity; this effect was not blocked by retinoids.

PMID- 9230198
TI  - Phenobarbital causes apoptosis in conditionally immortalized mouse hepatocytes
      depending on deregulated c-myc expression: characterization of an unexpected
      effect.
AB  - The CHST8 mouse hepatocyte cell line, conditionally immortalized with the
      temperature-sensitive SV40 large T antigen gene, rapidly proliferates at 33
      degrees C with active expression of the c-myc proto-oncogene but, due to the heat
      labile nature of the mutant T antigens, becomes growth arrested and
      morphologically senescent at 39 degrees C; this is accompanied by the
      disappearance of c-myc transcripts. In a previous study, we transfected the CHST8
      cells at 33 degrees C with an activated c-H-ras or a c-myc, both of which are
      frequently involved in mouse hepatocarcinogenesis in vivo. When the temperature
      was shifted to 39 degrees C, cells with only one of the exogenous oncogenes did
      not escape from the senescence, but those containing both exhibited an immortal
      phenotype. In the present study, using this in vitro model of
      hepatocarcinogenesis, we demonstrated that phenobarbital, a tumor promoter of
      rodent hepatocarcinogenesis, triggers remarkable apoptosis specifically in the c
      myc-transfected CHST8 cells at 39 degrees C, which show abundant c-myc expression
      despite growth arrest. Dissociation of p53 proteins from degrading T antigens
      followed by a phenobarbital and c-myc-dependent, 15-fold induction of Bax
      protein, known to activate the apoptotic pathway downstream of p53, occurred in
      association with this phenomenon. The effects of phenobarbital and c-myc in
      increasing Bax on shifting the temperature from 33 degrees C to 39 degrees C were
      additive, with both having similar degrees of influence on the protein level.
      Interestingly, subsequent introduction of an activated c-H-ras oncogene into the
      c-myc-transfected CHST8 cells resulted not only in escape from the growth arrest
      at 39 degrees C but also in complete inhibition of the phenobarbital-inducible
      apoptosis along with de novo induction of the Bax antagonist, Bcl-2. These
      findings strongly suggest that the phenobarbital-inducible apoptosis is mediated
      by Bax. Although it is a common notion that phenobarbital promotes liver tumor
      development through suppression of apoptosis, our results, together with the
      known fact that phenobarbital occasionally inhibits hepatocarcinogenesis in mice,
      indicate a problematic complexity in its biological activities.

PMID- 9230199
TI  - Genetic resistance to urethan-induced pulmonary adenomas in SMXA recombinant
      inbred mouse strains.
AB  - Development of pulmonary adenomas (PAs) in mice is under the genetic control of
      multiple host genes. We have established a new set of SMXA recombinant inbred
      strains from PA-susceptible A/J and PA-resistant SM/J mice. The number of urethan
      induced PAs was variable among substrains of the SMXA recombinant inbred strains,
      indicating the involvement of multiple genes. SMXA24 mice were highly resistant
      to PA, although they had susceptible alleles at all four known susceptibility
      genes, including kras2 and MHC. To identify the resistance gene in SMXA24,
      progeny of reciprocal F1 crosses and progeny of backcrosses to A/J were given
      urethan at 4 weeks of age and examined for induced PA at the age of 5 months. In
      reciprocal F1 cross progeny, the incidence of PA was very low, indicating that
      the resistance was a semidominant trait. Quantitative trait analysis of the
      backcross generation revealed significant linkages to loci on chromosome 12
      (logarithm of odds score, 6.47) and chromosome 11 (logarithm of odds score,
      4.35). To date, two PA resistance (PAR) genes, Par1 (located on chromosome 11)
      and Par2 (located on chromosome 18), have been reported. From the map position,
      one of the resistance genes on chromosome 11 was indistinguishable from Par1.
      However, another resistance gene on chromosome 12 was new, and we named this gene
      Par3. A likely candidate gene for Par3 is nPKCn, which is expressed exclusively
      in skin and lung and is down-regulated in PA. Par1 and Par3 seemed to act
      synergistically.

PMID- 9230200
TI  - Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats
      without reducing prostaglandin levels.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac, have cancer
      chemopreventive properties by a mechanism that has been suggested to involve
      cyclooxygenase inhibition and reduction of prostaglandin (PGE2) levels in the
      target tissue. To test this hypothesis, we studied the effect of dietary sulindac
      sulfone (500-2000 ppm), a metabolite of sulindac reported to lack cyclooxygenase
      inhibitory activity, on tumor formation and PGE2 levels in the azoxymethane model
      of colon carcinogenesis. Rats treated with sulindac at 400 ppm and piroxicam at
      150 ppm were used as positive controls. Rats received two s.c. injections of
      azoxymethane (15 mg/kg) for 2 weeks and were fed either experimental or control
      diets until necropsy. After 31 weeks of sulfone treatment, a dose-related
      increase in sulfone levels in both serum and cecal contents was measured; there
      was no evidence of metabolic conversion to sulindac or other metabolites. Rats
      treated with sulfone at 1000 and 2000 ppm, sulindac, and piroxicam had
      significantly fewer colonic adenomas and carcinomas compared with rats fed
      control diet as measured by tumor incidence, multiplicity, and tumor burden.
      Sulfone-treated rats also showed a dose-response relationship for inhibiting all
      tumor parameters. Colons from rats treated with sulindac or piroxicam contained
      PGE2 levels that ranged from approximately 16-49% of control levels. PGE2 levels
      in rats treated with sulfone up to 2000 ppm ranged from 78-118% of control
      levels. Moreover, the effects of sulindac sulfone on various enzymes responsible
      for regulating prostaglandin levels were evaluated. No significant inhibitory
      effects were observed for cyclooxygenase, lipoxygenase, or phospholipase A2.
      These results suggest that reduction of prostaglandin levels in the target tissue
      may not be necessary for the chemopreventive properties of sulindac.

PMID- 9230201
TI  - Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro
      angiogenesis.
AB  - Consumption of a plant-based diet can prevent the development and progression of
      chronic diseases associated with extensive neovascularization, including solid
      malignant tumors. In previous studies, we have shown that the plant-derived
      isoflavonoid genistein is a potent inhibitor of cell proliferation and in vitro
      angiogenesis. In the present study, we report that certain structurally related
      flavonoids are more potent inhibitors than genistein. Indeed, 3-hydroxyflavone,
      3',4'-dihydroxyflavone, 2',3'-dihydroxyflavone, fisetin, apigenin, and luteolin
      inhibited the proliferation of normal and tumor cells, as well as in vitro
      angiogenesis, at half-maximal concentrations in the low micromolar range. We have
      previously demonstrated that genistein concentrations in the urine of subjects
      consuming a plant-based diet is 30-fold higher than in subjects consuming a
      traditional Western diet. The wider distribution and the more abundant presence
      of flavonoids in the plant kingdom, together with the present results, suggest
      that flavonoids may contribute to the preventive effect of a plant-based diet on
      chronic diseases, including solid tumors.

PMID- 9230202
TI  - Tirapazamine-induced cytotoxicity and DNA damage in transplanted tumors:
      relationship to tumor hypoxia.
AB  - Tirapazamine (TPZ) is a hypoxia-selective bioreductive drug currently in Phases
      II and III clinical trials with both radiotherapy and chemotherapy. The response
      of tumors to TPZ is expected to depend both on the levels of reductive enzymes
      that activate the drug to a DNA-damaging and toxic species and on tumor
      oxygenation. Both of these parameters are likely to vary between individual
      tumors. In this study, we examined whether the enhancement of radiation damage to
      tumors by TPZ can be predicted from TPZ-induced DNA damage measured using the
      comet assay. DNA damage provides a functional end point that is directly related
      to cell killing and should be dependent on both reductive enzyme activity and
      hypoxia. We demonstrate that TPZ potentiates tumor cell kill by fractionated
      radiation in three murine tumors (SCCVII, RIF-1, and EMT6) and two human tumor
      xenografts (A549 and HT29), with no potentiation observed in a third xenograft
      (HT1080). Overall, there was no correlation of radiation potentiation and TPZ
      induced DNA damage in the tumors, except that the nonresponsive tumor xenograft
      had significantly lower levels of DNA damage than the other five tumor types.
      However, there was a large tumor-to-tumor variability in DNA damage within each
      tumor type. This variability appeared not to result from differences in activity
      of the reductive enzymes but largely from differences in oxygenation between
      individual tumors, measured using fluorescent detection of the hypoxia marker
      EF5. The results, therefore, suggest that the sensitivity of individual tumors to
      TPZ, although not necessarily the response to TPZ plus radiation, might be
      assessed from measurements of DNA damage using the comet assay.

PMID- 9230203
TI  - A tumor suppressor gene, Cx26, also mediates the bystander effect in HeLa cells.
AB  - The connexin 26 (Cx26) gene suppresses the growth of HeLa cells in vitro and in
      vivo. We explored the possibility that the Cx26 gene not only suppresses growth
      but can also mediate the bystander effect that is observed in some gene therapy.
      In gene therapy mediated by the herpes simplex virus thymidine kinase, the
      toxicity of ganciclovir affects not only the cells transduced with the gene but
      also affects neighboring tumor cells; it has been suggested that gap junctional
      intercellular communication (GJIC) may play a role in such a bystander effect.
      HeLa cells expressing the Cx26 gene (Cx26+) or not expressing the Cx26 gene were
      transfected with the herpes simplex virus thymidine kinase (tk+) gene, producing
      Cx26(-)-tk-, Cx26(-)-tk+, Cx26+-tk-, and Cx26+-tk+ cells. By making different
      kinds of cocultures of these cells, we observed a clear bystander killing effect,
      assessed by the neutral red toxicity test, in the coculture of Cx26+-tk-/Cx26+
      tk+ cells. The bystander effect was markedly prevented by a long-term inhibitor
      of GJIC, 18-alpha-glycyrrhetinic acid, demonstrating that a major part of the
      bystander effect seen occurred through Cx-mediated GJIC. These data suggest the
      possibility of using of Cxs as both tumor suppressor genes and as diffusers of
      ganciclovir toxicity in therapeutic approaches.

PMID- 9230205
TI  - Antitumor immune response of human peripheral blood lymphocytes coengrafted with
      tumor into severe combined immunodeficient mice.
AB  - Here, it is established that human peripheral blood lymphocytes (HuPBLs),
      injected s.c. with a human lung tumor into severe combined immunodeficient (SCID)
      mice, engraft and display antitumor cytotoxic activity. Initial studies used
      HuPBLs from normal donors and an allogeneic tumor cell line derived from biopsy
      tissue of a patient with a squamous cell carcinoma of the lung. Evidence of HuPBL
      antitumor activity was revealed by a cell dose-dependent suppression of the tumor
      xenograft. Tumor suppression was shown to be dependent upon both CD8+ T cells and
      CD56+ natural killer cells in the donor HuPBLs. By titrating the antitumor
      activity of HuPBLs in SCID mice with and without cytokines, it was established
      that interleukin (IL)-12 enhanced the HuPBL-mediated tumor suppression and that
      IL-2 had a synergistic effect upon the IL-12 enhancement of cytotoxicity.
      Subsequent studies revealed that a lung cancer patient's PBLs also suppress the
      growth of the patient's (autologous) tumor when coinjected s.c. with the tumor
      cells into SCID mice. The patient's antitumor immunity was shown to be mediated
      by CD8+ T cells and CD56+ natural killer cells. The data presented here indicate
      that the s.c. coengraftment of HuPBLs and tumor into SCID mice represents a
      viable model with which to study (and to periodically monitor) patients' immune
      responses to their tumors for extended periods of time and suggest that this
      SCID/Winn assay could be used to evaluate novel immunotherapeutic approaches,
      such as bolus injections of cytokines, cytokine gene therapy, or vaccination
      strategies for the treatment of human cancer.

PMID- 9230206
TI  - Infiltration of cervical cancer tissue with human papillomavirus-specific
      cytotoxic T-lymphocytes.
AB  - CTLs specific for high-risk human papillomaviruses (HPVs) have recently been
      found in the peripheral blood of cervical cancer patients. Although cell-mediated
      immunity is thought to be important in the control of HPV infection, the
      functional relevance and site of activation of HPV-specific CTLs are unclear. We
      identified HLA-A*0201-restricted HPV-16 E7 peptide-specific CTLs in the
      peripheral blood (four of five patients), draining lymph nodes (three of four
      patients) and tumors (one of three patients) of cervical cancer patients. In four
      of four cancer patients, the frequency of CTLs specific for a recombinant
      vaccinia virus expressing HPV-16 and -18 E6/E7 gene products was found to be
      higher in tumors and lymph nodes compared with that of peripheral blood. HPV
      specific CTLs were not identified in any of seven healthy controls, but primary
      responses could be generated by peptide-pulsed dendritic cells (four of four
      controls). In a non-HLA-A*0201 subject with invasive carcinoma, other HLA alleles
      also presented HPV antigens. This is the first demonstration that virus-specific
      CTLs infiltrate the virus-associated tumor, where they may play an important role
      in restricting disease progression.

PMID- 9230204
TI  - Methylator resistance mediated by mismatch repair deficiency in a glioblastoma
      multiforme xenograft.
AB  - A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in
      athymic nude mice was established by serially treating the parent xenograft D-245
      MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine,
      temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9
      aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG
      (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N
      nitrosourea, and busulfan, but they were sensitive to the other agents. Both D
      245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA
      alkyltransferase activity, and their levels of glutathione and glutathione-S
      transferase were similar. D-245 MG xenografts expressed the human mismatch repair
      proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

PMID- 9230207
TI  - Transformation properties of the ETO gene, fusion partner in t(8:21) leukemias.
AB  - The (8;21)(q22;q22) translocation, reported in 40% of M2-subtype acute myeloid
      leukemias (AMLs), is the second-most frequently observed example of a nonrandom
      genetic alteration associated with AML. Juxtaposition of the AML1 gene on
      chromosome 21 to the ETO gene on chromosome 8 fuses the NH2-terminal portion of
      AML1 to near-full length ETO, creating AML1/ETO. Previous work has been focused
      on perturbation of AML1 gene function by the chimeric fusion protein as a
      mechanism of leukemogenesis. Here, we demonstrate that ETO itself has
      transforming properties. Ectopic ETO expression in NIH/3T3 cells led to foci of
      transformation and colony growth in soft agar. ETO-expressing cells grew to
      higher saturation densities and induced tumors following injection into
      irradiated and splenectomized nude mice. Our data suggests that ETO may play an
      important role in the leukemic transforming potential of the AML1/ETO fusion
      protein.

PMID- 9230208
TI  - Mismatch repair in extracts of Werner syndrome cell lines.
AB  - Werner syndrome (WS) is an autosomal recessive disease, the phenotype of which is
      a caricature of premature aging. WS cells and cell lines display several types of
      genetic instability, and WS patients have an increased risk of developing cancer.
      The WS locus (WRN) encodes a protein that shows significant sequence homology to
      the RecQ family of DNA helicases. Because a DNA helicase may function in DNA
      mismatch repair, we examined extracts of WS cell lines for mismatch repair
      activity. Extracts from four different WS lymphoblastoid cell lines containing
      different WRN mutations and from three within-pedigree control cell lines were
      all proficient in mismatch repair. In marked contrast, extracts from three
      independent WS fibroblastoid cell lines were deficient in repair of base-base and
      insertion/deletion mismatches. Extracts of one of these lines restored activity
      to extracts of mismatch repair-deficient tumor cells with defined mutations in
      hMSH2, hMSH3, hMSH6, hMLH1, or hPMS2. This suggests that the WRN mutation in this
      fibroblast line is not a dominant negative inhibitor of mismatch repair activity
      and that the repair defect does not reside in these five known mismatch repair
      genes. Defective mismatch repair in fibroblastoid but not lymphoblastoid cells is
      consistent with the possibility that WRN protein could have a cell type- and/or
      tissue-specific role in mismatch repair. Alternatively, a mutation in WRN could
      predispose cells to mutations in other genes required for mismatch repair
      activity, at least one of which could be an unknown gene.

PMID- 9230209
TI  - CaSm: an Sm-like protein that contributes to the transformed state in cancer
      cells.
AB  - A novel gene encoding a protein containing Sm motif-like domains was found to
      have elevated expression in pancreatic cancer and in several cancer-derived cell
      lines. CaSm (for Cancer-associated Sm-like) mRNA is up-regulated in 87.5% (seven
      of eight) of pancreatic tumor/normal pairs. Similarly, cell lines from cancers
      originating in liver, ovary, lung, and kidney show increased CaSm expression
      compared to their normal tissue cognates. CaSm encodes a 133-amino acid open
      reading frame that contains the two Sm motifs found in the common snRNP proteins,
      with the greatest homology to the Sm G protein (60% similarity). Two hypothetical
      proteins from Caenorhabditis elegans and Saccharomyces cerevisiae share even
      greater similarity (72.8 and 67.7%, respectively), suggesting a broad family of
      proteins containing Sm motifs. Antisense CaSm RNA is able to alter the
      transformed phenotype of pancreatic cancer cells by reducing their ability to
      form large colonies in soft agar when compared to untransfected cells. Therefore,
      CaSm expression appears to be necessary for maintenance of the transformed state.

PMID- 9230210
TI  - Cloning and characterization of p10, an alternatively spliced form of p15 cyclin
      dependent kinase inhibitor.
AB  - We have cloned an alternatively spliced form of cyclin-dependent kinase (CDK)
      inhibitor p15 from human placenta. The alternative splice arises from an
      alternative 5' donor site in intron 1. An in-frame stop codon within the new
      exon, called exon 1beta, leads to translation of a Mr 10,000 protein identical to
      the NH2 terminus of p15 but contains a novel, basic COOH terminus. The
      alternatively spliced form, termed here as p10, is ubiquitously expressed in
      normal and tumor cell lines as shown by Northern hybridization and reverse
      transcription-PCR. Transforming growth factor beta1 induces the expression of p10
      similarly to p15 in human HaCaT keratinocytes. Expression and analysis of p15 and
      epitope-tagged p10 in cells by immunohistochemistry showed similar localization
      of both to the cytoplasm and nucleus in mink epithelial cells and cytoplasmic
      localization in mouse fibroblasts. Analysis of the effects of p10 and p15 on cell
      growth indicated that both were transiently growth inhibitory in Mv1Lu and NIH
      3T3 cells, but their stable expression did not significantly reduce the number of
      cell colonies. In contrast to p15, CDK4 and CDK6 did not coimmunoprecipitate p10
      in transient expression assays in COS-7 cells. Furthermore, overexpression of p10
      together with p15 in COS-7 cells did not interfere with the complex formation of
      p15 with CDK4 or CDK6. Thus, in the absence of detectable CDK binding, p10 is
      transiently able to restrain cell cycling, indicating that the alternative
      splicing of the CDK inhibitors presents further complexity in their regulation
      and functions.

PMID- 9230211
TI  - Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced
      apoptosis.
AB  - CDC 25 is a dual phosphatase responsible for dephosphorylation and, thus,
      activation of CDC 2 kinase in G2. Abnormal activation of cyclin B-associated CDC
      2 kinase has been implicated in apoptosis induced by cancer chemotherapeutic
      agents such as paclitaxel (Taxol) and etoposide (VP-16). In this study, we found
      that the CDC 2 kinase could be transiently activated when nasopharyngeal
      carcinoma NPC-TW01 cells were treated for 3 h with a new anticancer agent, GL331.
      GL331 treatment also induced a concomitant increase in CDC 25A phosphatase
      activity and a reduced level of Tyr-15-phosphorylated CDC 2 in NPC-TW01 cells.
      Furthermore, subsequent apoptotic DNA fragmentation induced by GL331 could be
      interrupted by treatment of the cells with the cyclin B1-specific antisense
      oligonucleotides, suggesting that abnormal activation of cyclin B1-associated CDC
      2 kinase and CDC 25A phosphatase was involved in GL331-induced apoptosis. Raf-1
      has been shown to associate with CDC 25A and, thus, to stimulate its phosphatase
      activity. Our results revealed that GL331 could facilitate the association of CDC
      25A with Raf-1, resulting in the cascade of CDC 25A phosphatase activation and
      CDC 2 kinase activation, as well as related signaling pathways, and ultimately
      causing apoptosis in cancer cells.

PMID- 9230212
TI  - Differential down-regulation of the UDP-glucuronosyltransferase 1A locus is an
      early event in human liver and biliary cancer.
AB  - One of the most important processes controlling cellular detoxification is
      carried out in the endoplasmic reticulum by glucuronidation, and most likely
      plays an important role in the defense mechanism against chemical-induced
      carcinogenesis. The human UDP-glucuronosyltransferase UGT1A locus encodes up to
      12 unique transferases that are transcribed through selective exon sharing.
      Little is known about how this locus is regulated in human tissues. We present
      evidence that the UGT1A gene products are differentially expressed in normal
      liver tissue, which is composed of hepatocellular and biliary tissue, as well as
      in malignant and premalignant tumor tissue. In liver, UGT1A1, UGT1A3, UGT1A4, and
      UGT1A9 are expressed, and are all significantly down-regulated in malignant
      hepatocellular carcinoma and its premalignant precursor, hepatic adenoma, but not
      in benign focal nodular hyperplasia. UGT1A6, which is expressed abundantly in
      liver, is not significantly regulated in liver tumors. UGT1A10, a newly
      discovered UGT1A gene product, is expressed only in biliary and not
      hepatocellular tissue and is also significantly down-regulated in
      cholangiocellular carcinoma. Differential regulation between normal biliary
      tissue and tumor is also observed with UGT1A4. These findings implicate the
      regulation of the UGT1A locus as a putative early event in hepatocarcinogenesis
      that discriminates between benign and malignant hepatotumorigenesis and indicates
      that a complex mode of cellular control underlies the regulation of this locus.

PMID- 9230213
TI  - p53-dependent p21 induction following gamma-irradiation without concomitant p53
      induction in a human peripheral neuroepithelioma cell line.
AB  - We previously generated cell hybrids between a derivative of the E6-containing
      HeLa cell line and a p53 null peripheral neuroepithelioma (PNET) cell line.
      Although p53 protein from the hybrids was genotypically wild type, it did not
      demonstrate wild-type behavior. Therefore, in the present study, we introduced
      wild-type p53 into the PNET parent to investigate whether p53 retained wild-type
      function within this cell line. Although the p53 null PNET parent lacked
      detectable p21 protein, introduction of wild-type p53 resulted in a detectable
      expression of p21 protein in all clones tested, suggestive of wild-type p53
      function. In addition, p53 expression was necessary for induction of p21 in
      response to irradiation, and, furthermore, we show this induction to occur at the
      transcriptional level. Although introduction of wild-type p53 seems to be
      responsible for p21 induction, the overall protein levels of p53 were not
      induced. The involvement of p53 in up-regulating p21 is further substantiated by
      the observation that p21 up-regulation was dependent on the introduction of the
      wild-type protein. Our results suggest that wild-type p53 is capable of up
      regulating p21 in response to DNA damage in the absence of p53 induction.

PMID- 9230214
TI  - Susceptibility to the development of pigment cell tumors in a clone of the Amazon
      molly, Poecilia formosa, introduced through a microchromosome.
AB  - The Amazon molly Poecilia formosa is a gynogenetic fish that reproduces through
      the development of ameiotic diploid eggs triggered by insemination by males of
      related species without following karyogamie. This leads to clonal offspring. In
      rare cases, however, this gynogenesis is leaky, and paternal DNA in the form of
      small supernumerary chromosomes is included into the maternal genome. We have
      obtained a clone where one such microchromosome contains a pigmentary locus,
      resulting in macromelanophore pigmentation of the carrier. Approximately 5% of
      these fish spontaneously develop exophytic nodular or papillomatous pigment cell
      tumors. The tumors display considerable differences with respect to growth
      characteristics and invasiveness, despite the genetic uniformity of the affected
      animals. Following transplantation to syngeneic hosts, a remarkable clonal
      variability was observed. Oncogenes that are involved in tumorigenesis in
      hereditary melanoma of the closely related fish Xiphophorus appear not to be
      instrumental for induction of the P. formosa pigment cell tumors. Moreover, a new
      genetic locus is defined that mediates susceptibility to pigment cell tumor
      development and leads to transformation of chromatoblasts.

PMID- 9230215
TI  - Clonal origin of adenovirus type 12-induced hamster tumors: nonspecific
      chromosomal integration sites of viral DNA.
AB  - The mechanism of tumor induction by human adenovirus type 12 (Ad12) in newborn
      Syrian hamsters (Mesocricetus auratus) has been investigated further. Tumors were
      produced in newborn hamsters by the s.c. injection of CsCl-purified Ad12. In 60
      70% of the surviving animals, tumors have been observed between 33 and 47 days
      after injection. In 60 independently elicited tumors, the patterns of Ad12 DNA
      integration have been studied by restriction enzyme analyses and Southern blot
      hybridization using Ad12 DNA or its terminal DNA fragments as hybridization
      probes. Moreover, the integrated viral genomes have been localized on different
      hamster chromosomes by the fluorescence in situ hybridization technique using
      either nonradioactively labeled digoxigenin probes and fluorescent antibodies or
      biotinylated probes and fluorescent avidin. In all of the tumors, 20 and more
      copies of viral DNA have been found covalently linked to cellular DNA, as
      apparent from the off-size restriction fragments that do not comigrate during
      electrophoreses with any of the known virion DNA fragments. In Ad12-induced
      tumors or Ad12-transformed hamster cell lines, there is no evidence for the
      persistence of nonintegrated, free viral DNA copies. In general, the multiple
      copies of Ad12 DNA are inserted into a single chromosomal cellular site, which is
      different for each tumor. Only in one tumor cell line have the integrated Ad12
      DNA copies been localized on two different chromosomes. The off-size fragment
      patterns generated by restriction and Southern blotting experiments are also
      unique and different for each tumor. These off-size fragments represent the sites
      of linkage between viral and cellular DNA but may also contain rearranged viral
      DNA sequences. We conclude that, upon Ad12 tumor induction in hamsters, Ad12 DNA
      does not integrate at specific insertion sites or nucleotide sequences into the
      cellular genome. It is still possible that selective elements exist at the sites
      of viral DNA insertion, e.g., specific chromatin structures due to
      transcriptional activity. The data presented also demonstrate (a) that each tumor
      cell carries Ad12 DNA; (b) that the insertion site appears to be the same in each
      tumor cell in a given tumor; (c) that, upon continued passage of the tumor cells
      in culture, the chromosomal site of Ad12 DNA insertion does not change, at least
      up to 25-32 passages, which correspond to about 75-96 cell generations beyond the
      tumor stage; and (d) that the integrated Ad12 DNA is localized on different
      chromosomes in individual tumors. Hence, the Ad12-induced tumors are of clonal
      origin. Another peculiarity of this viral tumor system is the frequent occurrence
      of more than one tumor in one animal. By the criteria established above, each
      individual tumor is characterized by its specific chromosomal integration site
      and restriction pattern. Thus, multiple induced tumors in one animal exhibit
      separate and individual clonality. During the time of maximally 7 weeks of
      observation of Ad12-induced tumors in the animals, metastases into different
      organ systems have not been observed.

PMID- 9230216
TI  - Human thymine-DNA glycosylase maps at chromosome 12q22-q24.1: a region of high
      loss of heterozygosity in gastric cancer.
AB  - Spontaneous hydrolytic deamination of 5-methylcytosine leads to T:G mismatches in
      double-stranded DNA and comprises a major threat for the integrity of both the
      DNA primary sequence as well as the epigenetic information stored in the DNA
      methylation pattern. Failure of the cellular DNA repair machinery to recognize
      and repair such mismatched nucleotides can lead to a mutator phenotype and
      subsequent carcinogenesis. A thymine-DNA glycosylase (TDG) has been described
      that initiates T:G mismatch repair by specifically excising the mismatched T. We
      have studied the TDG genomic locus and the expression of this enzyme to evaluate
      its role in cancer development. TDG is highly expressed in thymus and is
      expressed at lower levels in all human tissues analyzed. The TDG gene has 10
      exons covering a region of >25 kb and is located on chromosome 12q22-q24.1.
      Because gastric tumors have been shown to contain a high percentage of C-->T
      mutations at CpG sites, we used a microsatellite found in intron 8 of the TDG
      locus to screen gastric tumor samples for loss of heterozygosity. Although our
      analysis showed loss of heterozygosity in 10 of 24 samples (42%), none of those
      tumor samples revealed a mutation in the coding sequence of the remaining TDG
      allele as analyzed by single-strand conformational polymorphism. Expression of
      the TDG was not determined because of the limited availability of RNA in these
      primary tumor samples. At present, we have found no evidence that TDG is central
      to the development of gastric cancer, limiting the importance of TDG in T:G
      mismatch repair and subsequent carcinogenesis.

PMID- 9230217
TI  - Human ornithine decarboxylase-overproducing NIH3T3 cells induce rapidly growing,
      highly vascularized tumors in nude mice.
AB  - Overexpression of human ornithine decarboxylase (ODC) under the control of strong
      promoters induces morphological transformation of immortalized NIH3T3 and Rat-1
      fibroblasts [M. Auvinen et al., Nature (Lond.), 360: 355-358, 1992]. We
      demonstrate here that ODC-overproducing NIH3T3 cells are tumorigenic in nude
      mice, giving rise to rapidly growing, large fibrosarcomas at the site of
      inoculation. The tumors are capable of invading host fat and muscle tissues and
      are vascularized abundantly. To disclose the molecular mechanism(s) driving the
      tumorigenic, invasive, and angiogenic phenotype of the tumors, the ODC
      overproducing cell lines and tumor tissues were analyzed for the expression of
      various potential regulators and mediators of cell proliferation, matrix
      degradation, and angiogenesis. The tumorigenicity of ODC transformants was
      associated with elevated polyamine levels and down-regulated growth factor
      receptors. The invasiveness of the ODC-induced tumors could not be attributed to
      overexpression of various known extracellular matrix-degrading proteases or
      matrix metalloproteinases. The induction of the tumor neovascularization proved
      not to be elicited by vascular endothelial growth factor or basic fibroblast
      growth factor. Instead, the ODC-overexpressing cells appeared to secrete a novel
      angiogenic factor(s) that was able to promote migration of bovine capillary
      endothelial cells in collagen gels and increase the proliferation of human
      endothelial cells in vitro. In parallel, ODC-transformed cells displayed down
      regulation of thrombospondin-1 and -2, the negative regulators of angiogenesis.
      Thus, the induction of the angiogenic phenotype of the ODC transformants is
      likely due both to increased expression and secretion of the new angiogenesis
      stimulating factor(s) and decreased production and release of the antiangiogenic
      thrombospondins.

PMID- 9230218
TI  - Tumor-specific expression of cytochrome P450 CYP1B1.
AB  - Cytochrome P450 CYP1B1 is a recently cloned dioxin-inducible form of the
      cytochrome P450 family of xenobiotic metabolizing enzymes. An antibody raised
      against a peptide specific for CYP1B1 was found to recognize CYP1B1 expressed in
      human lymphoblastoid cells but not to recognize other forms of cytochrome P450,
      particularly CYP1A1 and CYP1A2. Using this antibody, the cellular distribution
      and localization of CYP1B1 were investigated by immunohistochemistry in a range
      of malignant tumors and corresponding normal tissues. CYP1B1 was found to be
      expressed at a high frequency in a wide range of human cancers of different
      histogenetic types, including cancers of the breast, colon, lung, esophagus,
      skin, lymph node, brain, and testis. There was no detectable immunostaining for
      CYP1B1 in normal tissues. These results provide the basis for the development of
      novel methods of cancer diagnosis based on the identification of CYP1B1 in tumor
      cells and the development of anticancer drugs that are selectively activated in
      tumors by CYP1B1.

PMID- 9230219
TI  - Enhanced degradation of I-kappaB alpha contributes to endogenous activation of NF
      kappaB in Hs294T melanoma cells.
AB  - The expression of the CXC chemokine MGSA is often deregulated during viral
      infection, chronic inflammation, and melanoma tumor progression. In Hs294T
      melanoma cells, the increased constitutive expression of MGSA is due to increased
      gene transcription. Moreover, nuclear extracts from unstimulated Hs294T cells
      contain 19-fold more immunoreactive NF-kappaB p65 than that observed in normal
      retinal pigment epithelial (ARPE) cells. This increase in NF-kappaB p65
      correlates with increased NF-kappaB DNA binding activity in Hs294T nuclear
      extracts. After stimulation with interleukin 1, Western and electrophoretic
      mobility shift assay analysis indicate that in both cell types, additional
      activated NF-kappaB p65 is translocated to the nucleus. However, the rate of
      postinduction repression of NF-kappaB DNA binding is delayed in Hs294T melanoma
      cells compared to ARPE cells. Western analysis of whole-cell lysates from both
      Hs294T and ARPE cells indicates that protein levels of the inhibitor of NF
      kappaB, I-kappaB alpha, are 3-fold lower in Hs294T cells. The decrease in I
      kappaB alpha cannot be attributed to alterations in the transcription or
      translation of I-kappaB alpha. Rather, the posttranslational processing has been
      altered. In Hs294T cells, the half-life of the I-kappaB alpha protein is 45 min,
      compared to 120 min in ARPE cells. These results indicate that in Hs294T melanoma
      cells the equilibrium between I-kappaB alpha degradation and resynthesis has been
      altered, leading to constitutive nuclear translocation and activation of NF
      kappaB. Similar mechanisms could also operate in other tumorigenic processes, as
      well as in viral and chronic inflammatory disorders, to produce high constitutive
      and unregulated chemokine expression.

PMID- 9230220
TI  - Suppression of experimental lung colonization of mouse colon adenocarcinoma 26 in
      vivo by an anti-idiotype monoclonal antibody recognizing a platelet surface
      molecule.
AB  - The interaction between platelets and tumor cells is important in the formation
      of pulmonary metastasis. We previously established the 8F11 monoclonal antibody
      (mAb) by immunizing rats with the NL-17 cell line, a highly metastatic variant of
      mouse colon adenocarcinoma 26. 8F11 could inhibit the platelet aggregation in
      vitro and suppress the pulmonary metastasis in vivo by NL-17 cells. 8F11
      recognized the Mr 44,000 sialoglycoprotein (gp44) on NL-17 cells, and the
      affinity-purified gp44 alone could induce platelet aggregation. Therefore, 8F11
      might inhibit gp44-induced platelet aggregation by masking the epitope of gp44
      that interacted with unknown molecule(s) on the platelet surface. To identify the
      platelet antigen that interacted with gp44, we generated anti-idiotype mAbs by
      immunizing rats with 8F11. Two of the established mAbs, AIP1 and AIP4, recognized
      not only 8F11 but also the Mr 160,000 platelet surface protein. AIP4 mAb could
      also inhibit the NL-17 cell-induced platelet aggregation in a dose-dependent
      manner. Furthermore, pretreatment of mice with AIP4 mAb suppressed the pulmonary
      metastasis of NL-17 cells in vivo. These results suggest that the Mr 160,000
      platelet antigen participates in the NL-17 cell-induced platelet aggregation and
      colonization of NL-17 cells in the lung by interacting with the gp44 of NL-17
      cells.

PMID- 9230221
TI  - Breast cancer cells have lower activating protein 1 transcription factor activity
      than normal mammary epithelial cells.
AB  - To determine whether normal breast cells have different levels of activating
      protein 1 (AP-1) expression and activation relative to breast cancer cells, we
      have compared the level of c-Jun and c-Fos expression and AP-1 activity in human
      mammary epithelial cells (HMECs) at different stages of transformation (normal
      proliferating HMECs, immortal HMECs, oncogene-transformed HMECs, and breast
      cancer cell lines). These studies demonstrated that normal and immortal HMECs
      have a high basal level of expression of cJun and cFos and higher AP-1 DNA
      binding and transcriptional activating activities than do oncogene-transformed
      HMECs or human breast cancer cells, with a gradual decrease in AP-1
      transactivating activity as cells progress through the carcinogenesis pathway
      (normal > immortal > oncogene-transformed > cancer cell lines). The AP-1 activity
      in normal or immortal cells was not modulated by growth factor supplementation or
      oncogene overexpression, as it is in breast cancer cells. However, the addition
      of suramin, a nonspecific growth factor antagonist, did inhibit AP-1 in these
      HMECs, suggesting that this high level of AP-1 present in normal HMECs may be due
      to autocrine stimulation of growth factor pathways. The differences in AP-1
      activity in normal and malignant breast cells may indicate that normal cells are
      more dependent on AP-1-mediated signals for their growth than are breast cancer
      cells.

PMID- 9230222
TI  - CaN19 expression in benign and malignant hyperplasias of the skin and oral
      mucosa: evidence for a role in regenerative differentiation.
AB  - CaN19, a member of the S100 family of calcium-binding proteins, is known to be
      "underexpressed" in cultured breast carcinoma-derived cell lines relative to
      their normal counterparts. By Northern blotting, we confirm these results and
      find that CaN19 is also markedly "underexpressed" in several carcinoma-derived
      cell lines of the skin, oral mucosa, and urogenital tract. However, exceptions to
      the inverse correlation between CaN19 expression and malignancy have been
      identified, bringing into question the hypothesis that CaN19 functions as a tumor
      suppressor gene. Unexpectedly, CaN19 mRNA was strongly expressed in bulk
      specimens of basal and squamous cell carcinomas of the skin and oral cavity.
      However, in situ hybridization revealed only limited CaN19 expression in tumor
      cells themselves; the bulk of expression is localized to hyperplastic
      perilesional epidermis. Tumor cell expression of CaN19 was similar in primary and
      locally metastatic tumors, indicating that this gene is not necessarily down
      regulated during tumor progression. Coordinate overexpression of CaN19 and the
      "hyperproliferalive" keratin K6a was observed only in tissues undergoing squamous
      differentiation. Taken together with other recent results from our laboratory,
      these findings suggest the hypothesis that CaN19 participates in an epidermal
      growth factor receptor-dependent pathway of regenerative squamous
      differentiation.

PMID- 9230224
TI  - Pulmonary gas exchange on Mount Everest.

PMID- 9230223
TI  - A.S. Lubbe et al., Preclinical experiences with magnetic drug targeting:
      tolerance and efficacy. Cancer Res., 56: 4694-4701, 1996; and Clinical
      experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin
      in 14 patients with advanced solid tumors. Cancer Res., 56: 4686-4693, 1996.

PMID- 9230225
TI  - Viruses and idiopathic pulmonary fibrosis.

PMID- 9230226
TI  - Airway mucus.

PMID- 9230227
TI  - Gas exchange at extreme altitude: results from the British 40th Anniversary
      Everest Expedition.
AB  - Since Messner and Habeler climbed to the summit of Mount Everest (8,848 m)
      without oxygen in 1978, there has been controversy between scientists trying to
      explain this feat. Field studies have suggested better respiratory performance
      than that found during a simulated climb in a hypobaric chamber, but the lack of
      data at extreme altitude has hampered the debate. We measured arterial oxygen
      saturation (Sa,O2) and alveolar partial pressure of oxygen (PA,O2) in nine
      subjects as they climbed from 3,500 to 8,000 m. Four of the climbers reached
      8,000 m and one reached the summit. We also tested the effects of breathing
      supplementary oxygen on Sa,O2 at 6,550 and 8,000 m. At all altitudes tested, we
      found that both PA,O2 and Sa,O2 were higher than expected from low pressure
      chamber studies. We also found that standard rates of supplementary oxygen (2 L x
      min(-1)) were insufficient to restore Sa,O2 above 90% at 8,000 m. The respiratory
      performance of climbers at extreme altitude is better than expected from sea
      level chamber studies, which may, in part, explain why humans can reach the
      summit (8,848 m) without added oxygen. The better performance is likely to be due
      to more appropriate acclimatization.

PMID- 9230228
TI  - Detection of adenovirus E1A DNA in pulmonary fibrosis using nested polymerase
      chain reaction.
AB  - The history of patients with idiopathic pulmonary fibrosis (IPF) shows that the
      disease may be preceded by a viral-like illness. Although viruses have not been
      demonstrated, it is possible that viruses were not detected in culture because
      they do not replicate during latency. We investigated the presence of adenovirus
      in IPF and interstitial pneumonia associated with collagen vascular disease (CVD
      IP), using the nested polymerase chain reaction (PCR) and in situ hybridization
      (ISH) for the E1A region of the adenovirus genome. Studies were performed on lung
      tissues obtained by transbronchial lung biopsy from 19 patients with IPF, 10
      patients with CVD-IP and, for comparison, from 20 patients with sarcoidosis. The
      E1A DNA was present in 3 out of 19 (16%) cases of IPF, in 5 of 10 (50%) cases of
      CVD-IP, and in 2 of 20 (10%) cases of sarcoidosis. The incidence of E1A DNA in
      CVD-IP was significantly higher than that in sarcoidosis (p<0.05). In patients
      with IPF and CVD-IP, E1A DNA was more prevalent in patients treated with
      corticosteroids (6 out of 9 cases; 67%) than in those without it (2 out of 20
      cases; 10%) (p<0.01). ISH studies showed that 1 out of 8 cases of IPF and CVD-IP,
      in which E1A DNA was detected by PCR, was positive for E1A DNA. We conclude that
      adenovirus E1A is unlikely to be aetiologically involved in the pathogenesis of
      idiopathic pulmonary fibrosis or interstitial pneumonia associated with collagen
      vascular disease. However, a latent adenovirus infection may be reactivated or
      may newly infect the host following corticosteroid administration.

PMID- 9230229
TI  - Relationship between respiratory muscle function and quality of life in
      sarcoidosis.
AB  - In sarcoidosis, pulmonary and general symptoms often do not correlate with
      radiographic stage and routinely performed lung function tests. Asymptomatic
      muscle involvement in sarcoidosis is common, but little is known about
      respiratory muscle involvement. The aim of this study was to investigate any
      relationships between persistent complaints and/or quality of life and
      respiratory muscle strength and endurance, respectively. Measurements of maximal
      inspiratory and expiratory mouth pressures (PI,max and PE,max), respiratory
      muscle endurance and routine lung function were made in 18 patients with
      sarcoidosis. To assess health status and quality of life, patients completed the
      Sickness Impact Profile (SIP). Respiratory muscle strength and endurance time
      were lower in the patient group than in a group of healthy controls (p=0.05).
      Compared to a general population, the patients with sarcoidosis were found to be
      limited in physical and psychosocial functioning. The respiratory muscle
      endurance time correlated with the SIP subscales "mobility" (r=-0.56; p<0.01),
      and "body care and movement" (r=-0.79; p<0.001). The total lung capacity (TLC),
      inspiratory vital capacity (IVC) and forced expiratory volume in one second
      (FEV1) were normal in all subjects. In conclusion, patients with sarcoidosis and
      normal lung function showed reduced respiratory muscle strength and endurance
      time. Correlations were found between these indices and both symptoms and certain
      Sickness Impact Profile domains. Therefore, we suggest inclusion of measurements
      of respiratory muscle strength in the assessment and follow-up of patients with
      sarcoidosis.

PMID- 9230230
TI  - Early diagnosis of lentivirus-induced infiltrative lung disease in sheep by high
      resolution computed tomography.
AB  - The visna-maedi lentivirus can induce an interstitial pneumonitis in sheep, and
      provides a convenient example to study natural or experimental lentiviral
      pathology. We wanted to determine whether high resolution computed tomography
      (HRCT) is able to detect early morphological changes following lentiviral
      infection in the lungs. Spontaneously infected adult sheep (n=3) and
      experimentally infected lambs (n=5) were compared to uninfected controls (n=4).
      The HRCT scans generally showed abnormal features in infected animals, including:
      increased parenchymal density; alveolar oedema; thickened interlobular septa; and
      increased density in peribronchiolar areas. HRCT was more sensitive than chest
      radiography for the early diagnosis of interstitial pneumonitis, although one
      sheep with advanced disease and radiographic and histopathological abnormalities
      had a paradoxically normal scan. One control animal showed minor abnormalities on
      scanning, which were probably due to the procedure used for anaesthesia. The HRCT
      observations were confirmed by postmortem histological examination of the lungs.
      In conclusion, high resolution computed tomography provides a noninvasive means
      of following the development of lung pathology in a natural ovine model of
      lentiviral disease.

PMID- 9230231
TI  - Higher asthma occurrence in an urban than a suburban area: role of house dust
      mite skin allergy.
AB  - Understanding of geographical differences in asthma prevalence may be helpful in
      explaining recent increases in the occurrence of asthma. We wondered whether
      differences in allergic sensitization or other factors could explain differences
      in reported occurrence of asthma between an urban centre and a neighbouring
      suburban area. From the European Community Respiratory Health Survey (ECRHS)
      questionnaire, responses on asthma symptoms and risk factors and results of 11
      skin allergy tests were available from 656 young adults living in urban or south
      suburban Antwerp, Belgium. Answers to five asthma questions were selected as
      dependent variables, and eight personal or environmental risk factors, as well as
      house dust mite (HDM) allergy, as independent variables. The effect of each
      independent variable on the association of asthma variables with area was
      assessed. Prior asthma diagnosis, present asthma symptoms, the selected risk
      factors and HDM allergy were all more frequently recorded in urban Antwerp.
      Difference in HDM allergy accounted for most of the difference in prior (mostly
      childhood) asthma diagnosis, since correction for it decreased the odds ratio
      from 2.10 to 1.65. On the contrary, the regional differences in recent asthma
      symptoms were not explained by HDM allergy differences nor by any other factor
      under study. This urban-suburban comparison indicated that house dust mite
      allergy is a major determinant of prior (childhood) asthma, whereas factors
      contributing to higher urban prevalence of present asthma symptoms could not be
      identified. Furthermore, our results indicate that it may be inappropriate to
      combine data from neighbouring areas, when their similarity has not been
      verified.

PMID- 9230232
TI  - Relationship between allergic manifestations and Toxocara seropositivity: a cross
      sectional study among elementary school children.
AB  - Toxocara (the cause of visceral larva migrans in humans) and allergy have in
      common both elevated immunoglobulin E (IgE) levels and eosinophilia. In the
      present study, we investigated: 1) associations between Toxocara seropositivity
      and allergic manifestations; 2) risk factors for Toxocara infection; and 3)
      differences in Toxocara seroprevalence, allergic manifestations and the
      associations between these two, in children from urban and rural environments.
      Blood samples from 1,379 Dutch urban and rural elementary schoolchildren, were
      examined for Toxocara antibodies, eosinophil numbers, total IgE concentrations,
      and the occurrence of inhaled allergen-specific IgE. Questionnaires investigating
      respiratory health and putative risk factors for infection were completed. It was
      found that 8% of the children had Toxocara antibodies, occurring significantly
      less often in females than in males. The means of total serum IgE levels and
      blood eosinophils were significantly higher in the Toxocara-seropositive than in
      the seronegative group. Allergic asthma/recurrent bronchitis was found in 7% of
      the children, allergic reaction on animal contact in 4%, and IgE to at least one
      inhaled allergen in 16%. These variables were associated with Toxocara
      seroprevalence. Inhaled allergen-specific IgE and asthma/recurrent bronchitis
      occurred significantly less often in rural than in urban areas, and significantly
      less often among girls than among boys. Furthermore, occurrence of allergen
      specific IgE increased significantly with age. No association existed between
      Toxocara seroprevalence and assumed risks, i.e. contact with pet animals and
      public playgrounds. In conclusion, our results indicate that allergic
      manifestations occur more often in Toxocara-seropositive children. A relationship
      with an already existing allergic condition is plausible.

PMID- 9230233
TI  - Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from
      atopic subjects prolongs eosinophil survival.
AB  - Eosinophilia is a feature of nasal polyposis. The aim of this study was to
      determine the role of cytokines and allergen in maintaining the eosinophilic
      infiltrate in this condition. Polyp fragments from house dust mite (HDM)
      sensitive atopic individuals and nonatopic individuals were cultured in the
      presence of HDM, or phytohaemagglutinin (PHA) or culture medium alone. Culture
      supernatants were assayed for interleukins (IL) 3, 5, and 8 and granulocyte
      macrophage colony stimulating factor (GM-CSF), and eosinophil survival enhancing
      activity (ESEA) in vitro. Significant ESEA was produced spontaneously. When polyp
      tissue from atopics, but not from nonatopics, was stimulated with allergen for 2
      days there was a further increase in ESEA associated with a median 12 and
      fourfold increase in IL-8 and GM-CSF, respectively. This increased ESEA was
      markedly reduced with anti-GM-CSF and, to a lesser extent, anti-IL-8 blocking
      antibodies. When stimulated with PHA, polyp tissue from atopic subjects also
      produced increased ESEA, implicating possible T-cell involvement. This was
      associated with a small (twofold), but significant, increase in IL-8 and a less
      consistent increase in GM-CSF. However, anti-IL-8 or anti-GM-CSF blocking
      antibodies failed to reduce the ESEA in these supernatants, suggesting
      involvement of other mechanisms. This study suggests that in sensitized
      individuals, allergen may contribute to polyp eosinophilia by stimulating the
      production of granulocyte/macrophage colony stimulating factor and interleukin 8.

PMID- 9230234
TI  - Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide
      in asthmatic patients.
AB  - Increased concentrations of exhaled nitric oxide (NO) occur in patients with
      asthma, and exhaled NO may be useful for assessing the effect of drug therapy on
      airway inflammation. Beta2-agonists have been proposed to have both
      proinflammatory and anti-inflammatory effects. We therefore assessed exhaled NO
      after beta2-agonists in asthmatic patients. Two randomized, double-blind, placebo
      controlled studies were conducted. Firstly, exhaled NO was measured in 18
      asthmatics (9 taking inhaled glucocorticosteroids (GCS)) before and after
      nebulized salbutamol (5 mg), or identical placebo (0.9% saline). Exhaled NO and
      forced expiratory volume in one second (FEV1) were measured at 15 min intervals
      for 1 h (Study 1). Secondly, the effect of 1 week of treatment with the long
      acting beta2-agonist, salmeterol (50 microg b.i.d.), added to either budesonide
      (800 microg b.i.d.) or placebo, was studied in eight mild asthmatic subjects
      (Study 2). Exhaled NO was measured by a chemiluminescence analyser, adapted for
      on-line recording. In Study 1, exhaled NO showed no significant change at any
      time-point in patients not taking inhaled GCS. In asthmatics on inhaled GCS,
      exhaled NO increased compared to placebo at 15 and 30 min, but this did not reach
      statistical significance. In Study 2, treatment with salmeterol increased FEV1,
      but exhaled NO levels were not significantly changed, either after budesonide
      treatment (143+/-35 to 179+/-67 ppb), or after placebo (201+/-68 to 211+/-65
      ppb). Our results confirm that single high dose salbutamol does not increase
      exhaled nitric oxide in asthmatics not taking inhaled glucocorticosteroids.
      Salbutamol may increase exhaled nitric oxide in asthmatics taking inhaled
      glucocorticosteroids. However, regular use of salmeterol resulted in no change in
      exhaled nitric oxide, either used alone or in combination with inhaled
      glucocorticosteroids.

PMID- 9230236
TI  - Distribution of inhaled fluticasone propionate between human lung tissue and
      serum in vivo.
AB  - High retention of inhaled glucocorticoids in the airways means prolonged anti
      inflammatory action and low delivery into the serum. The objective of this study
      was to investigate the retention in and distribution of inhaled fluticasone
      propionate (FP) between central and peripheral human lung tissue and serum in
      vivo. In 17 patients undergoing lung resection surgery, a single 1.0 mg dose of
      FP was inhaled at varying time-points (range 2.8-21.7 h) preoperatively.
      Peripheral and central lung tissue was obtained, and blood was drawn
      simultaneously. FP concentrations in central lung tissue were approximately three
      to four times higher than peripheral lung tissue concentrations, which in turn,
      exceeded those found in serum by 10 times. FP was detectable up to 21 and 16 h,
      respectively, after inhalation, with drug levels falling almost in parallel in
      peripheral lung tissue and in serum. The results of this study demonstrate that
      fluticasone propionate is retained in lung tissue for a long time. Serum
      concentrations after a single inhaled dose are low. Retention of high
      concentrations of fluticasone propionate in the airways may promote high topical
      anti-inflammatory activity.

PMID- 9230235
TI  - Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil
      survival and GM-CSF secretion.
AB  - Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may
      be due to an effect on the release of epithelial cell products responsible for
      promoting eosinophil survival. We investigated the effect of fluticasone
      propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the
      release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on
      eosinophil survival induced by secretions from cultured nasal epithelial cells.
      Human epithelial cell-conditioned media (HECM) were generated by cultured
      epithelial cells obtained from healthy subjects undergoing corrective nasal
      surgery. Normodense eosinophils isolated from peripheral blood were incubated
      with HECM generated with and without the drugs. All of the drugs tested inhibited
      eosinophil survival, and response was dose-dependent. Fluticasone propionate had
      the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M),
      followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25
      1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was
      the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M),
      followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25
      13x10(-8) M), and nedocromil sodium (IC25 >10(-5) M). A significant correlation
      was found between both inhibitory effects (r=0.955; p<0.05). Topical anti
      inflammatory drugs may decrease eosinophil survival by abrogating the promoting
      effect of epithelial cells. These drugs may exert part of their therapeutic
      effect by modulating GM-CSF release. The following rank of potency was observed:
      fluticasone propionate > budesonide > beclomethasone dipropionate > nedocromil
      sodium. The study of the interaction between epithelial cells and eosinophils may
      be a useful method for investigating and comparing the potency of topical drugs.

PMID- 9230237
TI  - Nedocromil sodium in obstructive airways disease: effect on symptoms and plasma
      protein leakage in sputum.
AB  - In patients with asthma or chronic obstructive pulmonary disease, there is
      chronic airway inflammation with increased leakage of plasma proteins into the
      airway lumen, which can be reduced by inhaled glucocorticosteroids. Nedocromil
      sodium is an anti-inflammatory drug, and we questioned whether it also affects
      the leakage of plasma proteins. In a double-blind placebo-controlled study we
      investigated the effect of 12 weeks of treatment with nedocromil on forced
      expiratory volume in one second (FEV1), provocative concentration of histamine
      causing a 20% fall in FEV1 (PC20), peak flow, symptom scores, and plasma protein
      leakage in sputum, in 31 patients with obstructive airways disease and sputum
      production (mean (range) FEV1 61% of predicted (42-87%); geometric mean (range)
      PC20 0.39 (0.04-2.9) mg x mL(-1)). As a measure for plasma protein leakage we
      calculated the relative coefficients of excretion (RCE) of proteins from serum to
      the soluble phase of sputum. There was a small increase in morning and evening
      peak flow (p<0.05) and a decrease in night-time bronchodilator use (p<0.02) in
      favour of nedocromil. The RCE of alpha2-macroglobulin to albumin significantly
      decreased after treatment with nedocromil (p=0.03). The results show limited
      clinical efficacy of nedocromil in our study group. They further suggest that the
      anti-inflammatory properties of nedocromil extend to inhibition of plasma protein
      leakage into the airways.

PMID- 9230238
TI  - Short-term knemometry and urine cortisol excretion in children treated with
      fluticasone propionate and budesonide: a dose response study.
AB  - Few thorough comparisons of the systemic effects of inhaled corticosteroids in
      children are available. The aim of this study was to compare the effect of
      budesonide and fluticasone propionate on short-term lower leg growth. Fluticasone
      propionate, budesonide and placebo were administered for 2 weeks in a randomized,
      double-blind, double-dummy, cross-over design. Twenty four children aged 6-12 yrs
      received 200 microg x day(-1) of each drug, or placebo. Another 24 children aged
      6-12 years received 400 microg x day(-1) of each drug, or placebo. Dry powder
      inhalers were used. Lower leg length was measured by knemometry twice a week
      during all three treatment periods, and 24 h cortisol excretion in the urine was
      measured at the end of each period. In the low-dose group, lower leg growth rate
      was the same during treatment with placebo (0.35 mm x week(-1)), fluticasone
      propionate (0.38 mm x week(-1)) or budesonide (0.26 mm x week(-1)). No
      significant difference (p=0.39) in lower leg growth rate was found between
      treatment with 400 microg x day(-1) budesonide (0.30 mm x week(-1)) and 400
      microg fluticasone propionate treatment (0.37 mm x week(-1)). Growth rate during
      treatment with budesonide, 400 microg x day(-1), was significantly lower than
      during placebo treatment (0.52 mm x week(-1)). Cortisol excretion in the urine
      during treatment with 200 microg x day(-1) fluticasone propionate was
      significantly reduced as compared with placebo (p=0.006), but not when compared
      with 200 microg x day(-1) budesonide (p=0.07). Budesonide 200 microg x day(-1)
      was not significantly different from placebo. Fluticasone propionate and
      budesonide, both at 400 microg x day(-1), resulted in a significant reduction in
      cortisol excretion in the urine as compared with placebo (p=0.001). It is
      concluded that, dose-for-dose, budesonide Turbuhaler and fluticasone propionate
      Diskhaler have similar systemic effects.

PMID- 9230239
TI  - Prevalence and intensity of rhinoconjunctivitis in subjects with occupational
      asthma.
AB  - Subjects with occupational asthma may also report symptoms of
      rhinoconjunctivitis. The aims of this study were: 1) to assess the prevalence of
      rhinoconjunctivitis in association with occupational asthma, and the severity of
      rhinoconjunctivitis according to the type of agent (high (HMW) and low (LMW)
      molecular weight agents) causing occupational asthma; and 2) to evaluate the
      timing of occurrence of symptoms of rhinoconjunctivitis in relation to those of
      occupational asthma. A questionnaire on symptoms of rhinoconjunctivitis and its
      timing in relation to the development of chest symptoms was prospectively
      addressed to 143 subjects consecutively referred to an occupational asthma
      clinic. Objective testing through specific inhalation challenges confirmed the
      diagnosis of occupational asthma in 40 subjects. Symptoms of rhinitis were
      reported at some time by 37 of the 40 subjects (92%), and of conjunctivitis by 29
      of the 40 subjects (72%). The prevalence of symptoms was not different for HMW
      and LMW agents, although rhinitis was more intense for HMW (19 out of 24 subjects
      with three or more of the following symptoms: runny nose, itchy nose, nasal
      blockage, and sneezing) than for LMW (5 out of 14 subjects) (p<0.01). There were
      significantly fewer subjects with occupational asthma due to LMW agents, with
      rhinitis appearing before asthma (p=0.03). Figures for conjunctivitis showed a
      similar trend, but did not reach statistical significance. In conclusion,
      symptoms of rhinoconjunctivitis are often associated with occupational asthma.
      Rhinitis is less pronounced in the case of low molecular weight agents, but more
      often appears before occupational asthma in the case of high molecular weight
      agents.

PMID- 9230240
TI  - Effects of repeated swine building exposures on normal naive subjects.
AB  - Exposure to swine confinement buildings has a negative impact on respiratory
      health. A short exposure to this environment results in an acute airway
      inflammatory response. The present study was performed to confirm and further
      define the acute effects of working in a swine building, and to determine whether
      these effects are reproducible. Seven previously nonexposed normal subjects
      underwent evaluations that included hourly measurement of forced expiratory
      volume in one second (FEV1), methacholine challenge (the provocative
      concentration producing a 20% fall in FEV1 (PC20)), bronchoalveolar lavage (BAL),
      nasal lavage (NL), and blood analyses, before (control) and after each of two 5 h
      exposures to a swine building environment. The exposures were conducted 8 days
      apart. The levels of total dust, endotoxins, and ammonia (NH3) in the confinement
      building were measured on each day of exposure. Both exposures resulted in a
      significant reduction in FEV1 (mean+/-SEM change in FEV1: control = 7+/-2%;
      exposure 1 = 15+/-3%; exposure 2 = 23+/-3%), decrease in PC20 (median value (25th
      75th percentile): 223 (23-256), 20 (15-198) and 20 (11-71), respectively; p=0.05)
      and increase in BAL cells (129+/-20, 451+/-43 and 511+/-103x10(3) cells x mL(-1),
      respectively) and NL cells (6+/-4, 126+/-58 and 103+/-26x10(3) cells x mL(-1),
      respectively), mostly neutrophils. Levels of interleukin-8 (IL-8), but not
      interleukin-1 (IL-1) or tumour necrosis factors (TNF-alpha), increased both in
      BAL and nasal fluids with exposure. In normal naive subjects, repeated exposure
      to the environment of a swine building induced a marked and reproducible
      reduction in forced expiratory volume in one second, increase in airway
      responsiveness, and increased neutrophilic inflammatory response. These results
      could not be accounted for by any of the environmental factors measured.

PMID- 9230241
TI  - Short-term ventilatory effects in workers exposed to fumes containing zinc oxide:
      comparison of forced oscillation technique with spirometry.
AB  - Following the occurrence of metal fume fever in some subjects after the
      installation of an electric furnace in a steel plant, a survey was undertaken to
      examine whether subjects exposed to fumes containing zinc oxide would exhibit a
      detectable impairment in ventilatory function, and whether a forced oscillation
      technique (FOT) was more suited for this detection than conventional spirometry.
      Pulmonary function measurements were made in 57 exposed workers (production or
      maintenance) and 55 nonexposed workers (maintenance or strandcasting department)
      at the beginning and near the end of a work shift (day or night). Maximal
      expiratory volumes and flows were measured by means of a pneumotachograph, and
      respiratory resistance (Rrs) and reactance at various frequencies by means of a
      FOT. These measurements were repeated 1 day later. During the day shift, there
      were no significant differences in pulmonary function between exposed and control
      workers. However, during the night shift, an influence of exposure on pulmonary
      function was revealed both by spirometry and by FOT: workers exposed at night
      showed a slight decrease in vital capacity (VC) and in forced expiratory volume
      in one second (FEV1), and a decline in respiratory resistance (Rrs) with
      oscillation frequency, that were more marked than in unexposed subjects. In
      contrast to the frequency dependence of Rrs, the changes of lung volumes and
      expiratory flows were related to differences in initial values between exposed
      and nonexposed workers. The decrease in FEV1 was maintained the day after
      exposure. The forced oscillation technique proved at least as sensitive as
      spirometry to detect small across-shift changes in ventilatory function. Although
      the effects on pulmonary function were small, it is likely that they represent a
      subclinical response to the inhalation of small quantities of zinc oxide.

PMID- 9230242
TI  - Community-acquired pneumonia: the annual cost to the National Health Service in
      the UK.
AB  - The aim of this study was to estimate the direct annual healthcare costs to the
      UK National Health Service (NHS) of managing community-acquired pneumonia. Using
      a prevalence-based burden of illness approach, health service resource use and
      corresponding costs attributable to the management of community-acquired
      pneumonia during 1992/1993 in the UK were obtained from published sources and
      commercial databases, and supplemented by a telephone survey of general
      practitioners, finance directors, community nurses, receptionists and nurses in
      out-patient respiratory clinics, ambulance services, and consultant respiratory
      physicians. The study was appraised by a Peer Review Panel, representing a cross
      section of experts from different locations. This study was a predefined subgroup
      analysis of a previous, larger study that estimated the annual cost to the NHS of
      treating all community-acquired lower respiratory tract infections. The analysis
      shows that there are 261,000 episodes of community-acquired pneumonia annually in
      the UK, costing 440.7 million pounds at 1992/1993 prices (32% of the annual cost
      for all community-acquired lower respiratory tract infections). Approximately
      83,153 annual cases of community-acquired pneumonia are treated in hospital (32%
      of all episodes) and account for 96% of the annual cost. The average cost for
      managing pneumonia in the community is 100 pounds per episode, compared to 1,700
      5,100 pounds when the patient is hospitalized, depending on the length of
      hospitalization. Hospitalization accounts for 87% of the total annual cost. In
      conclusion, community-acquired pneumonia in the UK incurs a direct healthcare
      cost of 440.7 million pounds annually at 1992/1993 prices. Developing and
      implementing strategies to prevent and minimize hospitalization will
      significantly reduce this annual cost and should be assessed in future studies.

PMID- 9230243
TI  - Attenuation of influenza-like symptomatology and improvement of cell-mediated
      immunity with long-term N-acetylcysteine treatment.
AB  - N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has
      been in clinical use for more than 30 yrs as a mucolytic drug. It has also been
      proposed for and/or used in the therapy and/or prevention of several respiratory
      diseases and of diseases involving an oxidative stress, in general. The objective
      of the present study was to evaluate the effect of long-term treatment with NAC
      on influenza and influenza-like episodes. A total of 262 subjects of both sexes
      (78% > or = 65 yrs, and 62% suffering from nonrespiratory chronic degenerative
      diseases) were enrolled in a randomized, double-blind trial involving 20 Italian
      Centres. They were randomized to receive either placebo or NAC tablets (600 mg)
      twice daily for 6 months. Patients suffering from chronic respiratory diseases
      were not eligible, to avoid possible confounding by an effect of NAC on
      respiratory symptoms. NAC treatment was well tolerated and resulted in a
      significant decrease in the frequency of influenza-like episodes, severity, and
      length of time confined to bed. Both local and systemic symptoms were sharply and
      significantly reduced in the NAC group. Frequency of seroconversion towards
      A/H1N1 Singapore 6/86 influenza virus was similar in the two groups, but only 25%
      of virus-infected subjects under NAC treatment developed a symptomatic form,
      versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a
      progressive, significant shift from anergy to normoergy following NAC treatment.
      Administration of N-acetylcysteine during the winter, thus, appears to provide a
      significant attenuation of influenza and influenza-like episodes, especially in
      elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus
      influenza infection but significantly reduced the incidence of clinically
      apparent disease.

PMID- 9230244
TI  - Pulmonary infection with Nocardia species: a report of 10 cases and review.
AB  - Pulmonary nocardiosis (PN) is an infrequent and severe infection due to Nocardia
      spp., microorganisms that may behave both as opportunists and as primary
      pathogens. The aim of this study and review was to evaluate the clinical
      features, evolution and prognostic factors of PN. The study group comprised 10
      consecutive patients with pulmonary nocardiosis acquired in a community setting,
      diagnosed and followed in a tertiary teaching hospital. Chronic obstructive
      pulmonary disease (COPD), neoplastic disease and human immunodeficiency virus
      (HIV) infection were the most frequent predisposing factors. Four patients were
      receiving corticosteroid treatment. Clinical course was chronic and diagnosis was
      delayed 3 weeks or more in seven of the patients. Lobar or multilobar
      condensation was the most frequent radiographic pattern. Antimicrobial
      susceptibility testing showed: 100% sensitivity for amikacin; 83% for imipenem;
      71% for cefotaxime; and 71% for trimethoprim-sulphamethoxazole. The disease
      remained localized in the lung in five cases, with a trend toward chronicity in
      one with bronchiectasis. In the other five, the disease disseminated, affecting
      subcutaneous tissue, the central nervous system and the kidney. Three patients
      died, one with disseminated disease and two who were receiving corticosteroid
      therapy. The following conclusions were reached: 1) pulmonary nocardiosis is
      difficult to diagnose, diagnosis is frequently delayed and a high level of
      suspicion is, thus, required in patients with underlying diseases or chronic
      corticosteroid therapy; 2) there is frequent dissemination and high mortality;
      and 3) antimicrobial combinations with proven synergy, such as imipenem and
      amikacin, are recommended for initial therapy.

PMID- 9230245
TI  - Prospective evaluation of computed tomography and mediastinoscopy in mediastinal
      lymph node staging.
AB  - Precise mediastinal lymph node (LN) staging is imperative in otherwise operable
      non-small cell lung cancer (NSCLC), as it determines subsequent treatment and
      possible inclusion in a neoadjuvant trial. The roles of mediastinoscopy and
      computed tomography (CT) remain controversial. To determine the accuracy of
      current CT scanners, a prospective study was performed. From April 1993 until
      September 1995, 100 consecutive patients with NSCLC without distant metastases
      underwent staging by CT and cervical mediastinoscopy. Naruke's map was used for
      classification, and LNs larger than 1 cm were considered CT positive. There were
      91 males and 9 females, with a mean age of 64 (range 45-82) yrs. Fifty nine
      tumours were central and 41 peripheral, 64 right-sided and 36 left-sided.
      Thoracotomy with mediastinal LN sampling was performed in 74 patients,
      nonoperated patients having multilevel stage IIIA or stage IIIB disease. Twenty
      five (25%) mediastinoscopies were positive and three were false-negative (3%).
      There were 29 false-positive CT scans and 12 false-negative. Overall sensitivity
      and specificity of CT were 63 and 57%, respectively, and of mediastinoscopy 89
      and 100%, respectively. Positive and negative predictive values of CT were 41 and
      77%, respectively, and of mediastinoscopy 100 and 96%, respectively. Accuracy of
      CT was 59% and of mediastinoscopy 97%. Accuracy of CT was lowest for left-sided
      and centrally located tumours, and for LN station 7. Even with current computed
      tomography scanners, sensitivity and specificity remain low. Although overall
      cost may increase, routine cervical mediastinoscopy is necessary for precise
      staging of non-small cell lung cancer, and subcarinal lymph nodes should be
      routinely sampled.

PMID- 9230246
TI  - Survey on the treatment of non-small cell lung cancer (NSCLC) in England and
      Wales.
AB  - As an adjunct to a meta-analysis of chemotherapy for non-small cell lung cancer
      (NSCLC), a survey was conducted in England and Wales of clinicians' views on the
      role of chemotherapy in NSCLC and the benefits it would have to offer to lead
      them to change their practice. Radiotherapists, medical oncologists, surgeons and
      physicians specializing in thoracic medicine, and physicians of palliative
      medicine were asked their views on the treatment of three case histories of 65 yr
      old men: Case 1, resected tumour involving a hilar lymph node (tumour (T)2, node
      (N)1, metastasis (M)0); Case 2, tumour that had spread to mediastinal lymph nodes
      bilaterally (T2, N3, M0); and Case 3, metastatic cancer (M1) accompanied by minor
      haemoptysis. Six hundred and ninety eight (85%) of the 821 clinicians responded.
      For Case 1, 74% would not recommend any adjuvant treatment, 24% would recommend
      radiotherapy, and <1% chemotherapy, and there was little expectation that
      adjuvant treatment would improve survival. For Case 2, 68% would recommend
      radiotherapy, 11% chemotherapy, and 1% surgery, 7% recommending a combination.
      Adjuvant treatment, regardless of modality, was expected to improve survival. For
      Case 3, only 11% would recommend chemotherapy, but 26% if the patient was aged <
      or = 50 yrs. There was little expectation of survival beyond 1 yr, or of
      improving survival with chemotherapy. For all three cases, most of those not
      recommending chemotherapy would require it to achieve substantially improved
      survival for them to use it routinely. Surgery alone is currently considered
      sufficient for resectable non-small cell lung cancer. Chemotherapy is rarely
      recommended for disease of any stage.

PMID- 9230247
TI  - Exercise testing in the preoperative evaluation of patients with bronchogenic
      carcinoma.
AB  - The aim of this study was to evaluate which parameters of preoperative spirometry
      and cardiopulmonary exercise test are the best predictors of postoperative
      morbidity and mortality in patients with bronchogenic carcinoma. Ninety seven
      patients were prospectively and consecutively examined. All patients had
      preoperative maximal exercise test and dynamic spirometry. Postoperative
      complications and causes of death were registered. Logistic regression was used
      and models explaining the relationship between preoperative variables and
      postoperative complications and deaths were constructed. We found significant
      differences in preoperative maximal workload and carbon dioxide output between
      groups, with and without cardiopulmonary-related complications, but not in
      spirometry variables. Logistic regression showed maximal workload to be the only
      predictor of cardiopulmonary complications. Maximal oxygen uptake was predictive
      of cardiopulmonary deaths. Maximal oxygen uptake and forced expiratory volume
      were predictive of postoperative complications. A maximal oxygen uptake <50%
      predicted was associated with high risk of death from cardiopulmonary causes.
      Kaplan-Meier survival curves showed that maximal oxygen uptake was correlated to
      long-term survival, while spirometric variables were not. Exercise testing can be
      used in the preoperative evaluation of patients with nonmetastatic bronchogenic
      carcinoma. A combination of the results of variables from spirometry and exercise
      testing is proposed to be used as a preoperative criterion for operability.

PMID- 9230248
TI  - Urokinase-type plasminogen activator in carcinomatous pleural fluid.
AB  - Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant
      cells during proliferation and migration, and is associated with tumour cell
      invasion and metastasis. This study was undertaken to evaluate whether u-PA is
      significantly increased in carcinomatous pleural fluids compared to those due to
      other aetiologies, and to identify the cells in the pleural space that are
      involved in its accumulation. Using an enzyme-linked immunosorbent assay, we
      quantified u-PA in the pleural fluid specimens of 40 patients with carcinomatous
      pleuritis, 18 with tuberculosis, 18 with parapneumonic pleuritis and 11 with
      congestive heart failure (CHF). The level of u-PA was elevated in carcinomatous
      pleural fluid compared with the level in transudative pleural fluid from patients
      with CHF (p<0.0001). The levels of u-PA were not statistically different between
      patients with cancer and tuberculosis, or between patients with cancer and
      pneumonia. The levels of u-PA in patients who did not respond to chemical
      pleurodesis were significantly higher than those who had complete response
      (p=0.0001). In immunocytochemical and immunoblotting studies, cancer cells in
      pleural fluids as well as mesothelial cells contained u-PA. u-PA was detected in
      the culture supernatants of viable pleural cells in the majority of patients with
      carcinomatous pleuritis. Our results suggest that local release of urokinase-type
      plasminogen activator by viable cells, including cancer cells and mesothelial
      cells, may affect the levels of urokinase-type plasminogen activator in pleural
      fluids.

PMID- 9230249
TI  - Home assessment of activities of daily living in patients with severe chronic
      obstructive pulmonary disease on long-term oxygen therapy.
AB  - In patients with severe chronic obstructive pulmonary disease (COPD) using long
      term oxygen therapy (LTOT), few studies have investigated activities of daily
      living (ADL). We examined the relationships between ADL, quality of life, mood
      state and airways obstruction in patients using long-term oxygen therapy (LTOT)
      and in patients not requiring LTOT. We studied 23 patients (14 males, 9 females;
      median age 71, range 60-84 yrs) with COPD who received LTOT using oxygen
      concentrators (LTOT group). We also studied a control group of 19 patients (14
      males, 5 females; median age 72, range 62-75 yrs) with COPD but without severe
      hypoxaemia (non-LTOT group). We found no significant difference between groups in
      health status using the St George's Respiratory Questionnaire (SGRQ). Median
      Nottingham Extended Activities of Daily Living (EADL) total scores were: LTOT
      group 10, non-LTOT 17; (p=0.01). Significant correlations (p<0.001) with
      Nottingham EADL score were found for Hospital Anxiety and Depression (HAD) score
      (rho=0.59), SGRQ Total score (rho=0.65) and percentage predicted forced
      expiratory volume in one second (FEV1) (rho=0.66). In conclusion, in patients
      with severe chronic obstructive pulmonary disease and broadly similar health
      status, those using long-term oxygen therapy were less independent in activities
      of daily living than those not requiring long-term oxygen therapy. Reduced
      independence in activities of daily living is, however, associated with the
      extent of airflow limitation, depression and poor health status, and does not,
      therefore, appear to be simply a result of restriction in movements imposed by
      the stationary device.

PMID- 9230250
TI  - Body composition and health-related quality of life in patients with obstructive
      airways disease.
AB  - This study evaluated the effects of body weight and lean mass abnormalities on
      health-related quality of life (HRQL) in obstructive airways disease. Body
      weight, lean mass (using dual-energy X-ray absorptiometry), and HRQL (using the
      St George's Respiratory Questionnaire (SGRQ)) were measured in 50 patients. Low
      lean mass was defined as a lean mass index (lean mass/height2) below the fifth
      percentile of a control population. Dyspnoea was measured by the baseline
      dyspnoea index. The mean (SD) age was 69+/-9 yrs; the forced expiratory volume in
      one second (FEV1) was 39+/-19% of predicted. Patients had 2.4+/-4.1 kg less lean
      mass than predicted. Increased dyspnoea was the most influential predictor of
      poor HRQL. Compared to normal-weight patients, those who were underweight had
      significantly greater impairment in activity, impact, and total SGRQ scores,
      while those who were overweight had greater impairment in impact and total SGRQ
      scores. Low lean mass was associated with greater impairment in symptoms,
      activity and impact subscores and the total SGRQ score. When dyspnoea was added
      to the model as a covariate, neither weight nor lean mass remained significantly
      related to HRQL. Thus, although body weight and lean mass abnormalities influence
      health-related quality of life, their effects appear to be mediated through
      increased levels of dyspnoea.

PMID- 9230251
TI  - Effects of psychotherapy in moderately severe COPD: a pilot study.
AB  - Anxiety is common in the "pink puffer" syndrome associated with chronic
      obstructive pulmonary disease (COPD). The degree of anxiety correlates well with
      perceived dyspnoea. This pilot study examines the effect of group psychotherapy
      on anxiety, exercise tolerance, dyspnoea and quality of life. Ten patients with
      moderately severe, stable COPD (mean forced expiratory volume in one second
      (FEV1)-1.15 L) had six 90 min sessions of cognitive and behavioural psychotherapy
      at weekly intervals. Patients completed the Hospital Anxiety and Depression Scale
      (HADS), Medical Research Council Questionnaire (MRCQ) and St George's Respiratory
      Questionnaires (SGRQ), 1 week before and after therapy. FEV1, forced vital
      capacity (FVC), slow vital capacity (SVC), blood gas tensions and 6 min walking
      distance (6MWD) were measured. Eight control patients attended weekly for lung
      function and 6MWD for 6 weeks, but had no psychotherapy. Mean baseline HADS score
      was significantly higher in the psychotherapy group (12) than in controls (7),
      but otherwise there were no differences in lung function, blood gas tensions,
      6MWD, or the other questionnaire scores between groups. After treatment, the
      physiological and psychological parameters where unchanged in both groups with
      the exception of the mean 6MWD, which had improved in the psychotherapy group
      only, from 351 to 423 m (p<0.001), an increase of 24%. Three months after
      treatment, the 6MWD was still 16% above the baseline value (p=0.02). In
      conclusion, six sessions of cognitive and behavioural psychotherapy produced a
      sustained improvement in exercise tolerance in a group of 10 anxious patients
      with severe chronic obstructive pulmonary disease, without any change in anxiety
      scores on the Hospital Anxiety and Depression Scale. Further studies of more
      prolonged, intensive psychotherapy would establish whether better symptom and
      quality of life scores accompany more dramatic increases in exercise tolerance in
      "pink puffers".

PMID- 9230252
TI  - A double-blind randomized trial of nicotine nasal spray as an aid in smoking
      cessation.
AB  - The objective of the study was to evaluate the therapeutic efficacy of nicotine
      nasal solution (NNS) for smoking cessation from the stopping day up to 3 months.
      We also followed the participants for 2 yrs after ceasing smoking to assess what
      happens after stopping using NNS. In a placebo-controlled, double-blind, 2 yr
      prospective study, 157 smokers were given either NNS, one dose containing 1 mg of
      nicotine per 100 microL (n=79), or placebo (n=78). Treatment was continued for up
      to 1 yr. One day after quitting smoking, the average number of daily doses was 11
      in the group assigned NNS and 14 in the group assigned the placebo, and after 6
      weeks, 14 and 6 doses, respectively, among abstinent participants still using
      spray. After 3 months, 65% of the abstainers in the nicotine group were still
      using the NNS. The abstinence rates were 51, 39 and 29% after 6 weeks, 3 and 6
      months, respectively, as compared to 24, 19 and 18% in the placebo group
      (p=0.0003; p=0.003; p=0.050). The proportion abstinent at the 1 yr (25 vs 17%)
      and 2 yr follow-ups (19 vs 14%) was higher among those assigned to the nicotine
      than to the placebo group, but not significantly so for the numbers used in the
      study. In conclusion, the use of nicotine nasal spray significantly increased the
      abstinence rate during the first 6 months following the quitting day.

PMID- 9230253
TI  - Published models and local data can bridge the gap between reference values of
      lung function for children and adults.
AB  - The aim of this study was to create reference equations for pulmonary function
      tests (PFTs) that span the age range from childhood to young adulthood. PFT
      results (forced vital capacity (FVC), forced expiratory volume in one second
      (FEV1), ratio of FEV1 to FVC (FEV1/FVC), total lung capacity (TLC), transfer
      factor) of 348 healthy 13-24 yr old Caucasian never-smokers from a local
      population study were compared with 13 selected sets of published reference
      equations. Predicted and observed PFT results differed significantly for 63 of 92
      reference equations tested, and most equations accounted poorly for the increase
      in PFT variables which takes place during adolescence. We selected the equations
      with the best fit and adjusted their parameters, so that the level and variance
      of predicted values agreed with the local data. For subjects older than 18 yrs,
      we selected the European Community for Steel and Coal (ECSC) equations. For
      subjects younger than 18 yrs, we chose European summary equations for FVC, FEV1,
      and FEV1/FVC, and recent British equations for TLC and transfer factor. The
      customized reference equations are the best available (maximum likelihood) for
      analysing PFTs of patients tested in our laboratory. Our approach can be used
      whenever generally accepted reference equations are lacking and a local sample of
      normal subjects is available.

PMID- 9230254
TI  - Measurement of the specific airway resistance by plethysmography in young
      children accompanied by an adult.
AB  - The purpose of this study was to evaluate a procedure for measurement of specific
      airway resistance (sRaw) by whole body plethysmography in young awake children
      accompanied by an adult. sRaw was measured by a single-step procedure, omitting
      the measurement of the thoracic gas volume. The frequency dependency of sRaw was
      investigated and the accuracy of simulating body temperature, atmospheric
      pressure and saturation with water vapour (BTPS) conditions by electronic
      compensation was assessed. One hundred and thirty one children with asthma were
      studied. In 57 children (mean (SD) age 5.6 (1.8) yrs) who performed measurements
      with and without an accompanying adult, the mean value of sRaw was 1.45 (0.36)
      and 1.44 (0.38) kPa x s, respectively, with a mean difference of 0.008 (0.152)
      kPa x s, and mean within-subject coefficients of variations (CV) of 8% and 10%,
      respectively. In 52 children (mean age 3.3 (0.8) yrs), for whom measurements made
      only in the presence of an accompanying adult, the CV was 8.5%. No measurements
      could be obtained in 22 children (17%) (mean age 2.8 (0.5) yrs). Measurements
      exhibited a significant frequency dependency, and electronic BTPS compensation
      substantially overestimated SRaw. In conclusion, the use of electronic
      compensation for simulating body temperature, atmospheric pressure and saturation
      with water vapour introduces a bias that affects the accuracy of the estimate of
      specific airway resistance. Nevertheless, plethysmographic measurements with and
      without an accompanying adult yielded comparable and equally repeatable estimates
      of specific airway resistance. The single-step plethysmographic procedure with an
      accompanying adult is a clinically useful method for evaluating airway function
      in children too young to perform plethysmographic measurements alone.

PMID- 9230255
TI  - Pulmonary function in infants with neonatal chronic lung disease with or without
      hyaline membrane disease at birth.
AB  - We studied whether neonatal chronic lung disease (NCLD), hyaline membrane disease
      (HMD) and differences in ventilatory support affected pulmonary function during
      the first year of life, in 65 infants born prematurely. The relationship between
      body weight and oxygen consumption (V'O2) was also analysed. The study comprised
      14 infants without cardiorespiratory disease, 19 infants with HMD but without
      NCLD, 9 infants with NCLD without prior HMD, and 23 infants with NCLD following
      HMD. At 6 and 12 months corrected postnatal age, static respiratory system
      compliance (Crs) was measured by weighted spirometry and the functional residual
      capacity by closed circuit helium dilution (FRCHe) combined with assessment of
      ventilation distribution from the mixing index (MI). Ventilatory support during
      the first 5 days of therapy was quantified from peak inspiratory pressure (PIP),
      mean airway pressure (MAP) and fractional inspiratory concentration of oxygen
      (FI,O2). Infants with NCLD had a shorter duration of gestation and lower birth
      weight than those without NCLD (Wilcoxon, p=0.002 and p=0.001, respectively).
      Pulmonary function at 6 and 12 months corrected age was not different between
      NCLD infants with or without HMD at birth. Infants with NCLD had lower Crs and MI
      than those without NCLD (analysis of variance (ANOVA), p<0.011), but their FRCHe
      was not different. V'O2 adjusted for body weight was comparable in the four
      groups. PIP and FI,O2 were higher (Wilcoxon, p<0.01) in the NCLD infants than in
      those with HMD alone, but MAP was not different. Except for FI,O2, these indices
      were not different among the infants with NCLD. We conclude that birth weight is
      the major determinant of the development of neonatal chronic lung disease. At 6
      and 12 months corrected age, the abnormal pulmonary function is not associated
      with prior hyaline membrane disease.

PMID- 9230256
TI  - Breathing pattern and respiratory mechanics in patients with amyotrophic lateral
      sclerosis.
AB  - The aim of this study was to evaluate the time course of breathing pattern and
      respiratory mechanics in patients with amyotrophic lateral sclerosis (ALS). A
      study was conducted on 25 out of 38 eligible ALS patients. Neurological status,
      arterial blood gases (ABGs), spirometry, breathing pattern (minute ventilation
      (V'E), tidal volume (VT), respiratory frequency (fR), duty cycle (duration of
      inspiration/duration of total breathing cycle (tI/ttot)), respiratory drive
      (P0.1)), respiratory mechanics (oesophageal pressure (Ppl), dynamic compliance
      (CL,dyn), pressure time product (PTP) and index (PTI), work of breathing (WOB)),
      and respiratory muscle (RM) strength as assessed by maximal oesophageal pressure
      (Ppl,max) were evaluated at presentation (to) in all patients and after 6 months
      (t6) in 11 patients. At to, the mean values of the degree of neurological
      impairment were 60+/-20 and 103+/-30 as assessed by the Norris scale and Medical
      Research Council (MRC) score, respectively. From the time of the first
      neurological symptom, survival time ranged 7-50 months. Diurnal ABGs were normal.
      A mild restrictive pattern was observed, a forced vital capacity (FVC) <70% of
      predicted being present in 45% of patients, only FVC % pred (r=0.59; p<0.05),
      forced expiratory volume in one second (FEV1) % pred (r=0.53; p<0.05) and
      survival (r=0.64; p<0.05) showing a significant correlation with the Norris
      scale. A Ppl,max <30 cmH2O was associated with a significantly greater mortality,
      Ppl,max being correlated with survival (r=0.79, p<0.05). At t6, fR, fR/VT,
      P0.1/Ppl,max, were significantly increased in comparison to to, while FVC % pred,
      vital capacity (VC) % pred, FEV1 % pred, VT and Ppl,max were significantly
      reduced. These results suggest a progressive deterioration in breathing pattern
      and in respiratory muscle strength with progression of disease.

PMID- 9230257
TI  - Respiratory mechanics in patients with tense cirrhotic ascites.
AB  - Lung volumes are decreased by tense ascites and increase after large volume
      paracentesis (LVP). The overall effect of ascites and LVP on the respiratory
      function is poorly understood. We studied eight cirrhotic patients with tense
      ascites before and after LVP. Inspiratory muscle force (maximal
      transdiaphragmatic pressure (Pdi,max), and the lowest pleural pressure (Pp1,min))
      was assessed while the patients were seated. Rib cage and abdominal volume
      displacements, as well as pleural and gastric pressures were measured during
      quiet breathing while the patients were supine. Pdi,max and Ppl,min were normal
      and did not change after LVP (from 84.2+/-19.7 to 85.2+/-17.0 cmH2O and from
      68.3+/-19.7 to 74+/-15.9 cmH2O, respectively). The abdominal contribution to the
      generation of tidal volume was greater than that of the rib cage (79 vs 21%), a
      pattern which did not change after LVP (73 and 27%). Before LVP, tidal swings
      both of pleural pressure (Ppl,sw) and transdiaphragmatic pressure (Pdi,sw) were
      large (15.3+/-4.3 and 18.5+/-3.9 cmH2O, respectively) and the load on inspiratory
      muscles was increased as a consequence of elevated dynamic elastance of the lung
      (El,dyn) (11.4+/-2.6 cmH2O x L(-1)) and ("intrinsic") positive end-expiratory
      pressure (PEEPi) (4.3+/-3.5 cmH2O). LVP reduced the load on the inspiratory
      muscles, as shown by the significant decrease in Ppl,sw (10.6+/-2.0 cmH2O),
      Pdi,sw (12.8+/-3.0 cmH2O), El,dyn (10.0+/-2.0 cmH2O x L(-1)) and PEEPi (1.1+/-1.3
      cmH2O). The amount of fluid removed was closely related to changes in Ppl,sw and
      PEEPi. We conclude that the strength of the inspiratory muscles is normal or
      reduced in seated cirrhotic patients. In the supine position, tense ascites
      results in an increase in lung elastic load and development of positive end
      expiratory pressure, with a consequent overload and increased activation of
      inspiratory muscles. Large volume paracentesis decreases overloading and
      activation, but does not change the strength of the inspiratory muscles.

PMID- 9230258
TI  - A new device for in vivo measurement of nasal transepithelial potential
      difference in cystic fibrosis patients and normal subjects.
AB  - Measurement of transepithelial potential difference (PD) on the nasal mucosa has
      been proposed to test for defective ion transport in cystic fibrosis (CF), and
      its possible correction after gene therapy or other treatments. The "classical"
      method records nasal PD under the inferior turbinate, with the disadvantage that
      the tip of the electrode is not seen by the operator. We have developed a purpose
      designed perfusion electrode for PD recording on the visible, medial/posterior
      aspect of the turbinate. We wanted to determine whether such PD recordings
      adequately discriminate between CF patients and normal subjects. Measurements of
      baseline PD and response to a standardized perfusion protocol were performed in
      20 normal subjects and 12 CF patients. Solutions of amiloride, with or without
      low chloride buffer were applied for 3 min. Increased baseline PD and
      depolarization after amiloride discriminated CF patients from normal subjects.
      Only one CF patient overlapped with the normal range. Superfusion of low chloride
      buffer with amiloride and terbutaline caused repolarization in 18 out of 20
      normal subjects (90%), consistent with physiological Cl- secretion process, but
      in none of the CF patients. We conclude that measurements of potential difference
      on the medial/posterior aspect of the turbinate can discriminate between cystic
      fibrosis patients and normal subjects. At this site, visual control of the
      measurement is possible, and the mucosa is easily accessible for subsequent
      cytological sampling or biopsy.

PMID- 9230259
TI  - A new use for an old Holter monitor: an ambulatory cough meter.
AB  - Cough is commonly used as an outcome measure in clinical studies, although the
      subjective reporting of cough is unreliable when compared to objective measures.
      We describe an inexpensive new ambulatory cough meter that is based on a disused
      Holter monitor. The cough meter consists of a Holter monitor and a cough
      processor, designed on a computer to select the most appropriate filters. The
      cough meter was then validated against the overnight tape recorder on 21
      occasions in 18 children (aged 6-15 yrs). The agreement between the cough meter
      and the tape recorder was good (mean difference of -0.3 coughs x h(-1); limits of
      agreement -2.2 to 1.7 coughs x h(-1)). We conclude that our newly described
      ambulatory cough meter provides a valid and inexpensive method of objectively
      monitoring cough for up to 24 h.

PMID- 9230260
TI  - Glucocorticoid-resistant asthma: pathogenesis and clinical implications for
      management.
AB  - At the present time, emphasis is placed on viewing asthma as a manifestation of
      chronic airway inflammation, possibly secondary to allergen hypersensitivity.
      Consequently, one aspect of management is to institute measures of environmental
      control to minimize the inflammatory response related to allergen stimulation,
      and to administer anti-inflammatory therapy to resolve inflammation and prevent
      progression of disease. Most patients respond very favourably to conventional
      therapy, as recommended in recent guidelines for asthma management. Some cases,
      however, remain very difficult to control despite high-dose inhaled
      glucocorticoids, even combined with oral glucocorticoid therapy. Management of
      these patients raises questions about the conditions that alter response to
      glucocorticoid therapy. The patient with difficult to control asthma not only
      presents a challenge to clinical management but raises new questions concerning
      our ability to control the progression of disease. Is difficult to control asthma
      secondary to overwhelming or ongoing allergen exposure? Do anti-inflammatory
      medications, specifically inhaled glucocorticoids, really control the progression
      of the disease? Are these patients destined to become severe asthmatics at birth
      due to the inherent characteristics of their airways, or is this indeed a
      consequence of progressive inflammation? This review will summarize present
      concepts of glucocorticoid-resistant asthma, current knowledge of the mechanisms
      of persistent inflammation, and the implications for management. The gaps in
      information will also be addressed in order to stimulate interest in further
      research that could lead to better understanding of the disease and potential
      windows for therapeutic intervention.

PMID- 9230261
TI  - Pleurodesis: state of the art.
AB  - Pleurodesis aims to achieve a symphysis between parietal and visceral pleural
      surfaces, in order to prevent accumulation of fluid or air in the pleural space.
      Its major indications are malignant effusions and pneumothorax, and a re
      expandable lung is essential for the success of the technique. Moreover,
      expectation of a reasonably long survival is important before attempting
      pleurodesis. A successful lung re-expansion is unlikely if the pleural pressure
      falls more than 20 cmH2O x L(-1) of fluid removed, because there is a central
      bronchial obstruction or the lung is trapped by tumour and/or fibrin. Pleural
      fluid pH (<7.20) is a good indicator of the presence of trapped lung; moreover, a
      successful pleurodesis is less likely when pH is low, and this parameter is also
      a good predictor for survival of the patients. Among the many sclerosing agents
      that have been used for pleurodesis, talc has achieved the best results, with an
      average success rate of approximately 90%. The cellular and biochemical
      mechanisms involved in pleurodesis may be specific to the agent used, however,
      they may all follow a common final pathway leading to activation of the pleural
      coagulation cascade, the appearance of fibrin networks, and the proliferation of
      fibroblasts. The details of these mechanisms are still unclear and need to be
      further elaborated.

PMID- 9230262
TI  - Airway mucosa: secretory cells, mucus and mucin genes.
AB  - The airway mucosa is lined by a continuous epithelium comprised of multiple cell
      phenotypes, several of which are secretory. Secretions produced by these cells
      mix with a variety of macromolecules, ions and water to form a respiratory tract
      fluid that protects the more distal airways and alveoli from injury and
      infection. The present article highlights the structure of the mucosa,
      particularly its secretory cells, gives a synopsis of the structure of mucus, and
      provides new information on the localization of mucin (MUC) genes that determine
      the peptide sequence of the protein backbone of the glycoproteins, which are a
      major component of mucus. Airway secretory cells comprise the mucous, serous,
      Clara and dense-core granulated cells of the surface epithelium, and the mucous
      and serous acinar cells of the submucosal glands. Several transitional phenotypes
      may be found, especially during irritation or disease. Respiratory tract mucins
      constitute a heterogeneous group of high molecular weight, polydisperse richly
      glycosylated molecules: both secreted and membrane-associated forms of mucin are
      found. Several mucin (MUC) genes encoding the protein core of mucin have been
      identified. We demonstrate the localization of MUC gene expression to a number of
      distinct cell types and their upregulation both in response to experimentally
      administered lipopolysaccharide and cystic fibrosis.

PMID- 9230263
TI  - Pulmonary hyperinflation and ventilator-dependent patients.
AB  - Pulmonary hyperinflation is a major medical problem in patients with advanced
      chronic obstructive pulmonary disease (COPD) or acute asthma. The apparent
      beneficial effects of pulmonary hyperinflation on lung mechanics, such as an
      increased airway patency and lung elastic recoil, are by far overwhelmed by the
      deleterious effects on the pressure generating capacity of the respiratory
      muscles. Moreover, the ventilatory workload can be remarkably increased: 1) by
      the displacement of the respiratory system toward the upper, flat portion of the
      pressure-volume curve; 2) by the need to expand the chest wall and not only the
      lungs; and 3) by the intrinsic positive end-expiratory pressure (PEEPi)
      systematically associated with dynamic hyperinflation. In mechanically ventilated
      patients, the mechanisms underlying pulmonary hyperinflation as well as its
      pathophysiological consequences do not differ from those described in
      spontaneously breathing patients. However, there are some specific issues that
      should be taken into account, namely the effect of the endotracheal tube and the
      mode and setting of the ventilator. In mechanically ventilated patients,
      pulmonary hyperinflation increases the risk of barotrauma and may hamper weaning
      due to the excessive burden of PEEPi, which can even lead to ineffective
      inspiratory efforts. Because of its harmful consequences, pulmonary
      hyperinflation must be treated aggressively by pharmacological therapy and, when
      needed, by ventilatory treatment. The setting of the ventilator must be
      predetermined to ensure the longest possible time for expiration, and positive
      end-expiratory pressure can be applied to prevent an excessive workload for the
      patient and ineffective inspiratory efforts.

PMID- 9230264
TI  - Superior vena cava syndrome caused by encapsulated pleural effusion.
AB  - Pleural effusion is often a manifestation of the superior vena cava (SVC)
      syndrome. However, pleural effusion has never been reported to be a cause of the
      SVC syndrome. We report the case of a 68 yr old male patient who presented with
      SVC syndrome and respiratory failure, both attributable to an encapsulated
      pleural effusion over the right upper mediastinum. Simple drainage was performed
      as a diagnostic and therapeutic procedure. The pleural effusion was confirmed to
      be a tuberculous empyema. Chest computed tomography (CT) scan is the most
      appropriate initial diagnostic procedure for superior vena cava syndrome.

PMID- 9230265
TI  - Gastropleural fistula due to gastric lymphoma presenting as tension pneumothorax
      and empyema.
AB  - The formation of a gastropleural fistula is an uncommon complication of a number
      of conditions. The case of a patient with gastropleural fistula, as a
      complication of gastric lymphoma, is presented. The patient developed a tension
      pneumothorax and empyema. On cytological examination of the empyematous fluid,
      the presence of food debris aided diagnosis. The patient died 2 days after a
      total gastrectomy. The development of this complication in gastric lymphoma
      appears to have a particularly poor prognosis.

PMID- 9230266
TI  - Clinical, radiographic and lung function features of diffuse congenital cystic
      adenomatoid malformation of the lung in an adult.
AB  - Congenital cystic adenomatoid malformation of the bronchi with bilateral lung
      involvement has only previously been reported in one possible adult case. This
      report describes a young man with bilateral diffuse lung involvement,
      characteristic histological features, and a mixed restrictive/obstructive lung
      function pattern.

PMID- 9230267
TI  - Exhaled and nasal nitric oxide measurements: recommendations. The European
      Respiratory Society Task Force.

PMID- 9230268
TI  - Bacterial colonization as a potential source of nosocomial respiratory infections
      in spirometers.

PMID- 9230269
TI  - Genotypes of glutathione transferase M1 and P1 and their significance for lung
      DNA adduct levels and cancer risk.
AB  - The A-G polymorphism at codon 104 in the glutathione S-transferase P1 (GSTP1)
      gene was examined in 138 male lung cancer patients and 297 healthy controls. The
      patients had significantly higher frequency of the GG genotype (15.9%) and a
      lower frequency of AA (38.4%) than the controls (9.1% and 51.5%, respectively).
      The level of hydrophobic DNA-adducts were determined in lung tissue from 70
      current smokers. Patients with the GG genotype had a significantly higher adduct
      level than patients with AA (15.5 +/- 10.2 vs 7.9 +/- 5.1 per 10(8) nucleotides,
      P = 0.006). We also analyzed the deletion polymorphism in the GSTM1 gene in 135
      male patients and 342 controls. The patients were stratified according to
      histology, smoking dose, age, adduct level and mutational types found in the
      tumors (Ki-ras and p53 genes). The results consistently indicated that the GSTM1
      null genotype was associated with a slightly increased lung cancer risk. When the
      combined GST M1 and P1 genotypes were examined, patients with the combination
      null and AG or GG had significantly higher adduct levels than all other genotype
      combinations (P = 0.011). The distribution of combined genotypes was also
      significantly different in cases and controls, mainly due to increased frequency
      of the combination GSTM1 null and GSTP1 AG or GG among patients.

PMID- 9230270
TI  - Aflatoxin B1-induced DNA adduct formation and p53 mutations in CYP450-expressing
      human liver cell lines.
AB  - Epidemiological evidence has been supporting a relationship between dietary
      aflatoxin B1 (AFB1) exposure, development of human primary hepatocellular
      carcinoma (HCC) and mutations in the p53 tumor suppressor gene. However, the
      correlation between the observed p53 mutations, the AFB1 DNA adducts and their
      activation pathways has not been elucidated. Development of relevant cellular in
      vitro models, taking into account species and tissue specificity, could
      significantly contribute to the knowledge of cytotoxicity and genotoxicity
      mechanisms of chemical procarcinogens, such as AFB1, in humans. For this purpose
      a non-tumorigenic SV40-immortalized human liver epithelial cell line (THLE cells)
      which retained most of the phase II enzymes, but had markedly reduced phase I
      activities was used for stable expression of the human CYP1A2, CYP2A6, CYP2B6 and
      CYP3A4 cDNA. The four genetically engineered cell lines (T5-1A2, T5-2A6, T5-2B6
      and T5-3A4) produced high levels of the specific CYP450 proteins and showed
      comparable or higher catalytic activities related to the CYP450 expression when
      compared to human hepatocytes. The T5-1A2, T5-2A6, T5-2B6 and T5-3A4 cell lines
      exhibited a very high sensitivity to the cytotoxic effects of AFB1 and were
      approximately 125-, 2-, 2- and 15-fold, respectively, more sensitive than the
      control T5-neo cells, transfected with an expressing vector which does not
      contain CYP450 cDNA. In the CYP450-expressing cells, nanomolar doses of AFB1
      induced DNA adduct formation including AFB1-N7-guanine, -pyrimidyl and -diol
      adducts. In addition, the T5-1A2 cells showed AFM1-DNA adducts. At similar levels
      of total DNA adducts, both the T5-1A2 and T5-3A4 cells showed, at codon 249 of
      the p53 gene, AGG to AGT transversions at a relative frequency of 15x10(-6). In
      contrast, only the T5-3A4 cells showed CCC to ACC transversion at codon 250 at a
      high frequency, whereas the second most frequent mutations found in the T5-1A2
      cells were C to T transitions at the first and second position of the codon 250.
      No significant AFB1-induced p53 mutations could be detected in the T5-2A6 cells.
      Therefore, the differential expression of specific CYP450 genes in human
      hepatocytes can modulate the cytotoxicity, DNA adduct levels and frequency of p53
      mutations produced by AFB1.

PMID- 9230271
TI  - Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is
      associated with colorectal tumours containing a GC-->AT transition in the K-ras
      oncogene.
AB  - O6-alkylguanine DNA-alkyltransferase (ATase) provides protection against the
      toxic, mutagenic and carcinogenic effects of alkylating agents, principally by
      removing the promutagenic lesion O6-alkylguanine from DNA. Differences in ATase
      activity in human tissue may thus determine mutational susceptibility. As GC-->AT
      transitions, which can be induced by O6-alkylguanine in DNA, are commonly
      observed in the K-ras oncogene of alkylating agent induced animal tumours and in
      human colorectal tumours, we have examined whether differences in ATase activity
      may affect the risk of K-ras mutations in humans with colorectal tumours. NTase
      activity in normal tissue from individuals with a K-ras mutation in colorectal
      tissue and more specifically a GC-->AT transition (but not a transversion
      mutation) was significantly lower than that in individuals without a mutation (P
      < 0.01). Thus, individuals with low ATase activity in normal tissue (i.e. below
      the median) were at increased risk of having a transition (OR 10.1; 95% CI 1.9
      99.0), but not a transversion mutation (OR 1.7; 95% CI 0.3-12.2). There were no
      significant differences in tumour ATase activity in individuals with or without a
      mutation. These results suggest that ATase can protect colorectal tissue against
      the mutagenic effects of alkylating agents and furthermore, that alkylating agent
      exposure plays a role in the aetiology of colorectal tumours containing a GC-->AT
      transition in the K-ras oncogene.

PMID- 9230272
TI  - Decreased hepatocyte growth factor level by Wy-14,643, non-genotoxic
      hepatocarcinogen in F-344 rats.
AB  - We examined the role of hepatocyte growth factor (HGF) in the
      hepatocarcinogenesis caused by [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]
      acetic acid (Wy-14,643), a peroxisome proliferator. Wy-14,643 (100 mg/kg body wt
      or 0.1% (w/w) in diet) was given orally to male F-344 rats for up to 78 weeks. At
      78 weeks the hepatocarcinomas or adenomas in the livers of Wy-14,643-treated rats
      were observed. Markedly decreased amounts of hepatic HGF mRNA were observed in
      rats fed Wy-14,643 for 78 weeks. The degree of reduction was higher in the tumour
      portions of the liver than in the normal portions. After 7 days of treatment with
      Wy-14,643 (100 mg/kg body wt), the expression of hepatic HGF mRNA was slightly
      decreased. Wy-14,643 treatment resulted in a time-dependent decrease in hepatic
      HGF mRNA levels to 63% of the control level after 14 days of treatment. In long
      term treatment (18-40 weeks), hepatic HGF mRNA levels were reduced further,
      reaching 44% of the control level at the 40-week stage. As shown by ELISA, the
      amounts of hepatic and plasma HGF were significantly decreased by 60 and 50%,
      respectively, compared with controls. The degree of the reduction correlated with
      the level of hepatic HGF mRNA. In the lung and kidney, also HGF secretory organs,
      Wy-14,643 slightly reduced the amount of HGF mRNA. In the colony assay using
      preneoplastic or neoplastic cells from Wy-14,643-treated livers, 5-15 ng/ml of
      HGF, which induces proliferation in normal hepatocytes, inhibited the colony
      formation of neoplastic or preneoplastic cells. The inhibitory effect was
      dependent on HGF concentration. In the presence of 300 ng/ml HGF, the growth of
      colonies was suppressed to 36% of the control level. These findings indicate that
      reductions in hepatic HGF levels, induced by Wy-14,643, may play an important
      role in the promotion of neoplastic or preneoplastic cell growth.

PMID- 9230273
TI  - Site- and strand-specific mismatch repair of human H-ras genomic DNA in a
      mammalian cell line.
AB  - Defective mismatch repair has recently been implicated as the major contributor
      towards the mutator phenotype observed in tumour cell lines derived from patients
      diagnosed with hereditary non-polyposis colon cancer (HNPCC). Cell lines from
      other cancer-prone syndromes, such as xeroderma pigmentosum, have been found to
      be defective in nucleotide excision repair of damaged bases. Some genetic
      complementation groups are defective specifically in transcription-coupled
      excision repair, although this type of repair defect has not been associated with
      cancer proneness. Mechanisms contributing to the high incidence of activating
      point mutations in oncogenes (such as H-ras codon 12) are not understood. It is
      possible that novel mechanisms of misrepair or misreplication occur at these
      sites in addition to the above DNA repair mechanisms. In this study, we have
      compared the rate of strand-directed mismatch repair of four mispairs (G:A, A:C,
      T:C and G:T) at the H-ras codon 12, middle G:C position. Our results indicate
      that, although this location is not a 'hot spot' for bacterial mismatch repair,
      it is a 'hot spot' for decreased repair of specific mismatched bases within NIH
      3T3 cells. NIH 3T3, unlike Escherichia coli, have an extremely low repair rate of
      the G:A mispair (35%), as well as the A:C mispair (58%) at this location. NIH 3T3
      also have a moderately low repair rate of the T:C mispair (80%) at the codon 12
      location. Conversely, NIH 3T3 repair of G:T (100%) is comparable to E. coli
      repair (94%) of this mismatch. These results demonstrate that a mismatch
      containing an incorrect adenine on either strand at the H-ras codon 12 middle
      base pair location is most likely to undergo a mutational event in NIH 3T3 cells.
      Conversely, a mismatch containing an incorrect thymine in the transcribed strand
      is least likely to undergo a mutational event.

PMID- 9230274
TI  - Changes in the expression of gap junction proteins (connexins) in hamster tongue
      epithelium during wound healing and carcinogenesis.
AB  - We examined changes in the expression and localization of connexin proteins and
      transcripts by means of immunofluorescence and in situ hybridization in normal
      conditions, wound healing and carcinogenesis using hamster tongue epithelium, in
      which differentiation, migration and growth of keratinocytes takes place
      physiologically and pathologically. In normal hamster tongue epithelium,
      immunofluorescent staining showed that Cx26 and Cx43 proteins were localized
      differently during differentiation of keratinocytes, but in in situ
      hybridization, the localization of Cx26 and Cx43 transcripts overlapped
      considerably, suggesting that the different localization of Cx26 and Cx43
      proteins in squamous epithelium is largely regulated at post-transcriptional
      levels. During wound healing, the expression and localization of connexin
      proteins and transcripts were changed drastically. Shortly (6 h) after injury the
      expression of Cx26 and Cx43 proteins decreased at wound edges, but by 1-3 days
      after injury the expression of both proteins increased and both proteins co
      localized to the same spots in the epithelium near wound edges. During
      carcinogenesis, the increased expression of Cx26 and Cx43 proteins and their
      transcripts and co-localization of both proteins occurred in papillomas, and the
      expression of Cx26 was reduced as cancer cells became morphologically less
      differentiated. We also found, that during wound healing in papillomas, squamous
      cell carcinomas and keratinocytes, Cx26 and Cx43 proteins were localized
      aberrantly in the cytoplasm, especially around nuclei, rather than on plasma
      membranes. These results indicate that quantitative and qualitative changes in
      connexin expression are associated with differentiation, migration and
      proliferation of keratinocytes in squamous epithelium.

PMID- 9230275
TI  - Folate, vitamin B12, homocysteine status and chromosome damage rate in
      lymphocytes of older men.
AB  - Deficient levels of folic acid and vitamin B12 are associated with elevated
      chromosome damage rate and high concentrations of homocysteine in the blood. We
      have therefore performed a study to determine the prevalence of folate
      deficiency, vitamin B12 deficiency and hyperhomocysteinemia in 64 healthy men
      aged between 50 and 70 years, and evaluate the relationship of these
      micronutrient levels in the blood with the micronucleus frequency in peripheral
      blood lymphocytes. We also performed a placebo-controlled, double-blind
      intervention study to determine whether supplementation of the diet with a daily
      dose of 0.7 mg (as a supplement in cereal) or 2.0 mg (in a tablet) over a period
      of 4 months resulted in a significant alteration of folate status, homocysteine
      status and the micronucleus index. Twenty-three per cent of the men were serum
      folate deficient (<6.8 nmol/l), 16% were red blood cell folate deficient (<317
      nmol/l), 4.7% were vitamin B12 deficient (<150 pmol/l) and 37% has plasma
      homocysteine levels >10 micromol/l. In total, 56% of the men had one or more
      abnormal blood values for folate, vitamin B12 or homocysteine. The micronucleus
      index of these men (n = 34) in cytokinesis-blocked binucleated cells (19.2 +/-
      1.1) was significantly elevated (P = 0.02) when compared to the micronucleus
      index of the rest of the men who had normal levels of folate, vitamin B12 and
      homocysteine (16.3 +/- 1.3, n = 30). Interestingly, the micronucleus index in men
      with normal folate and vitamin B12, but homocysteine levels >10 micromol/l (19.4
      +/- 1.7, n = 15) was also significantly higher (P = 0.05) when compared to those
      with normal folate, vitamin B12 and homocysteine. This novel result was also
      supported by the observation that the micronucleus index and plasma homocysteine
      were significantly (P = 0.0086) and positively correlated (r2 = 0.172) in those
      subjects who were not deficient in folate or vitamin B12. The micronucleus index
      was not significantly correlated with folate indices, but there was a significant
      (P = 0.013) negative correlation with serum vitamin B12 (r2 = 0.099). Daily
      supplementation of the diet with 0.7 mg free folic acid in cereal for 2 months
      followed by 2.0 mg free folic acid via a tablet produced a 4-fold increase in
      plasma folate, a 2.6-fold increase in red blood cell folate and a 11% reduction
      in plasma homocysteine; however, these changes were not accompanied by a
      reduction in the micronucleus index. In conclusion, it is apparent that elevated
      homocysteine status, in the absence of vitamin deficiency and low, but not
      deficient, vitamin B12 status are important risk factors for increased chromosome
      damage in lymphocytes.

PMID- 9230276
TI  - Suppression of azoxymethane-induced rat colon carcinoma development by a fish oil
      component, docosahexaenoic acid (DHA).
AB  - The effects of intragastric gavage administration of docosahexaenoic acid (DNA) ,
      a major component of fish oil, on azoxymethane (AOM)-induced colon carcinogenesis
      in rats was investigated. Male F344 rats were treated with 15 mg/kg body wt of
      AOM once a week, for two weeks. The animals were given either 1 ml of DHA or
      water intragastrically 5 times a week, starting the day before the first
      carcinogen treatment. The numbers of AOM-induced aberrant crypt foci in the rats
      given DHA were 76% and 62% of the control values, at 4 and 12 weeks,
      respectively. After 36 weeks of DHA treatment, colon tumors were counted and
      examined histologically. The blood plasma levels of prostaglandin E2 (PGE2) and
      polyunsaturated fatty acids were also quantified. The incidences of colon cancer
      did not differ, being 96% and 92% in the AOM and AOM+DHA groups, respectively.
      Colon cancer multiplicity was, however, significantly decreased by the DHA
      treatment; 3.65 +/- 2.18 in the AOM group and 2.41 +/- 1.58 in the AOM+DHA group
      (P <0.01). Notably, the numbers of moderately differentiated adenocarcinomas in
      the middle and distal colon in the DHA-treated group were lower than in the AOM
      group. The levels of PGE2 and arachidonic acid in the blood plasma of DHA-treated
      rats were also significantly lower than in the AOM group. These results suggest
      that DHA exerts its inhibitory effect on colon carcinogenesis by modulating lipid
      metabolism and inhibiting the arachidonic cascade.

PMID- 9230277
TI  - Effects of administration of the chemoprotective agent oltipraz on CYP1A and
      CYP2B in rat liver and rat hepatocytes in culture.
AB  - The success of oltipraz (OPZ) [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] as
      a chemoprotective agent against aflatoxin B1 (AFB1)-induced hepatocarcinogenesis
      in the rat is thought to depend principally on its ability to enhance
      detoxication by inducing phase II enzymes, especially glutathione transferases.
      However, in primary cultures of human hepatocytes, we recently demonstrated that
      OPZ also has an important inhibitory effect on the major cytochromes P450 (CYPs)
      of human hepatic AFB1 metabolism. This has prompted a detailed study of the
      effect of OPZ on some CYPs involved in metabolism of AFB1 in the rat. Primary
      cultures of rat hepatocytes behaved similarly to human hepatocytes and responded
      to OPZ by inhibition of ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin
      O-depentylase (PROD) activities mainly associated, respectively, with CYP1A and
      CYP2B. A time-course shows that this inhibition is largely reversible, with EROD
      and PROD activities reaching a minimum at 12 h and tending towards control values
      within 24 h. As is to be expected, the incubation of isolated microsomes with OPZ
      also inhibits CYP1A and 2B. The effect of OPZ on CYP1A is not a phenomenon
      limited to cells in culture, but also occurs in vivo. Using the whole animal, we
      were able to demonstrate that OPZ also transiently inhibited CYP1A activity in a
      rat given caffeine, by measuring the amounts of methylxanthines found in the
      serum. However, microsomes isolated from rats, that had been treated with OPZ in
      vivo, show no such inhibition, presumably because, since OPZ is a reversible
      inhibitor, it dissociates and is lost during the course of conventional
      procedures of microsomal preparation. This explains some earlier failures in
      studies of isolated microsomes to observe the inhibition of CYPs by OPZ. In
      addition to inhibiting their enzymatic activity, OPZ is also an inducer of CYP1A
      and 2B as shown by the increased levels of their mRNAs and of caffeine metabolism
      in vivo after 24 h or more. It is concluded that the mechanism of chemoprotection
      by OPZ, of toxic chemical metabolism in the rat, is complex and involves
      competitive inhibition of activation succeeded by induction of the enzymes of
      both activation and detoxication.

PMID- 9230278
TI  - Relationship between acetylator status, smoking, and diet and colorectal cancer
      risk in the north-east of England.
AB  - Some previous studies have suggested that the fast phenotype of the N
      acetyltransferase NAT2 may confer susceptibility to colorectal cancer because of
      greater activation of dietary heterocyclic amines, particularly in individuals
      who also consume well-done red meat, but other studies have not supported this.
      We describe a large case-control study examining the interaction between dietary,
      smoking and drinking habits, and acetylation genotype in relation to
      susceptibility to colorectal cancer. One-hundred-and-seventy-four incident cases
      and 174 matched controls were recruited. Genotyping for polymorphisms in NAT2 was
      performed using a method that detects >95% of slow alleles and data on personal
      habits were collected using a standardized questionnaire. We found no difference
      in the frequency of the fast acetylator genotype between cases and controls [odds
      ratio = 0.95 (95% CI 0.61-1.49)], and analysis by sex, age and site also revealed
      no difference in acetylator genotype. There was, however, considerable
      heterogeneity in dietary risk factors between fast and slow acetylators. Analysis
      by acetylator type shows that recent smoking was more frequent in slow acetylator
      cases than matched controls [OR = 2.31 (1.16-4.6)] and that heavy alcohol
      consumption was also more frequent in the slow acetylator cases than controls [OR
      = 2.5 (1.02-7.29)]. In contrast, frequent fried meat intake was seen more
      frequently in fast acetylator cases than matched controls [OR = 6.0 (1.34-55)].
      The odds ratio for the combination of fast acetylator status and frequent fried
      meat consumption in cases was 6.04 (1.6-26). Our study suggests that there may be
      different risk factors for colorectal cancer in slow and fast acetylators, and
      reveals a new observation that slow acetylators may be at risk of colon cancer
      from smoking. In our community, the overall effect of acetylator status on
      colorectal cancer risk is neutral.

PMID- 9230279
TI  - Differences in the p53 gene mutational spectra of prostate cancers between Japan
      and Western countries.
AB  - Mutations of the p53 gene are related to development of human cancers and their
      frequencies and spectra, the latter representing fingerprints left by
      carcinogens, provide information about the molecular epidemiology of the disease.
      Prostate cancer is the most common neoplasm in American males and although its
      incidence is still relatively low in Japanese people, it has recently been
      increasing with the westernization of life style. To assess the frequency and
      spectrum of p53 gene mutations in Japanese prostate cancers, we examined a series
      of 90 lesions using polymerase chain reaction (PCR)-single-strand conformation
      polymorphism (SSCP) analysis. The patients' mean age was 69.3 years (range 57
      87). Of the total, six were well-, 34 moderately- and 50 poorly-differentiated
      adenocarcinomas, and the median Gleason score was 7.9. Eleven of the 90 cases
      (12%) had mutations in exons 2-11 of the p53 gene: none of the five clinical
      stage A, one of 25 stage B (4%), three of 35 stage C (9%) and seven of 25 stage D
      (28%) cancers. The correlation with an advanced stage was statistically
      significant. One insertion and 10 base pair substitutions were encountered,
      comprising six transversions (55%) and four transitions (36%). Two of the latter
      involved methylated cytosine-guanine (CpG). These 11 mutations were combined with
      18 other mutations in previous reports concerning Japanese prostate cancers to
      facilitate comparison of the p53 gene mutational spectrum with those reported for
      American and European prostate cancers. In the latter, 61% were transitions and
      33% were transversions. The greater proportion of transversions in the Japanese
      population suggests that there are different factors responsible for
      carcinogenesis of the prostate glands in the various countries.

PMID- 9230280
TI  - Synergistic induction of DNA strand breakage by cigarette tar and nitric oxide.
AB  - Cigarette smoking is a major cause of human cancer at a variety of sites,
      although its carcinogenic mechanisms remains unestablished. Cigarette smoke can
      be divided into two phases, gas phase and particulate matter (tar). Both phases
      contain high concentrations of oxidants and free radicals, especially nitric
      oxide (NO) and nitrogen oxides in the gas phase and quinone/hydroquinone complex
      in the tar. We have found that incubation of pBR322 plasmid DNA with aqueous
      extracts of cigarette tar and a NO-releasing compound (diethylamine NONOate)
      caused synergistic induction of DNA single-strand breakage, whereas either
      cigarette tar alone or NO alone induced much less strand breakage. This
      synergistic effect of cigarette tar and NO on DNA strand breakage was prevented
      by high concentrations of superoxide dismutase, carboxy-PTIO (an NO-trapping
      agent) or N-acetylcysteine, whereas hydroxyl radical scavengers such as
      dimethylsulfoxide, ethanol and D-mannitol did not show inhibitory effects.
      Possible mechanisms for this synergistic effect mediated by cigarette tar and NO
      are proposed, including involvement of peroxynitrite, which is a strong oxidant
      and nitrating agent formed rapidly by the reaction between NO and O2.-. NO is
      present in the gas phase of smoke and may be formed by a constitutive or
      inducible NO synthase in the lung, whereas O2.- is generated by auto-oxidation of
      polyhydroxyaromatic compounds such as catechol and 1,4-hydroquinone present in
      cigarette tar. Thus, potent reactive species including peroxynitrite formed by
      the interaction between cigarette tar and NO may play an important role in
      smoking-related diseases including lung cancer.

PMID- 9230282
TI  - Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant
      crypt foci inhibition.
AB  - Oligofructose and inulin, naturally-occurring fermentable chicory fructans, have
      been shown to stimulate the growth of bifidobacteria which are regarded as
      beneficial strains in the colon and inhibit colon carcinogenesis in the
      laboratory animal models. The present study was designed to determine the effect
      of oligofructose and inulin on the azoxymethane (AOM)-induced preneoplastic
      lesions such as aberrant crypt foci (ACF) formation in the colon of male F344
      rats. At 5 weeks of age, groups of animals were fed the AIN-76A (control) and the
      experimental diets containing 10% oligofructose or inulin. At 7 weeks of age, all
      animals received s.c. injection of AOM dissolved in normal saline at a dose rate
      of 15 mg/kg body wt, once weekly for 2 weeks. The animals were necropsied 7 weeks
      after the last AOM injection, and the ACF were visualized under light microscopy
      in the formalin-fixed, unsectioned methylene blue-stained colons. They were
      distinguished by their increased size, more prominent epithelial cells and
      pericryptal space. The feeding of oligofructose or inulin significantly inhibited
      the ACF formation and the crypt multiplicity in the colon. The degree of ACF
      inhibition was more pronounced in animals fed inulin than in those fed
      oligofructose. The findings suggest that chicory fructan supplements inhibit ACF
      formation, an early preneoplastic marker of malignant potential in the process of
      colon carcinogenesis.

PMID- 9230281
TI  - Power frequency magnetic fields do not contribute to transformation of JB6 cells.
AB  - The potential for power frequency magnetic fields to enhance neoplastic
      transformation has been investigated in vitro using promotion-sensitive mouse
      epidermal JB6 cells. In a soft agar assay, 60-Hz magnetic fields of 0.01, 0.1,
      1.0, or 1.1 mT flux density did not induce anchorage-independent growth. In
      addition, these magnetic fields did not enhance tumor promoter-induced
      transformation showing no increase in the maximum number of transformed colonies
      and no shift in the dose-response curve. Thus, these data do not support the
      notion that environmental exposures to magnetic fields contribute to
      transformation.

PMID- 9230283
TI  - Induction of cathepsin D protein during estrogen carcinogenesis: possible role in
      estrogen-mediated kidney tubular cell damage.
AB  - We have proposed that an early step in estrogen carcinogenesis in the hamster
      kidney is tubular damage followed by reparative cell proliferation. This tubular
      injury is progressive and increases in severity with continued estrogen
      treatment; one pertinent feature is a marked rise in the number of both secondary
      and tertiary lysosomes. Data presented herein indicate that cathepsin D, an
      estrogen-responsive lysosomal proteolytic enzyme, is increased in the kidney
      following estrogen treatment in the hamster. Three isoforms of cathepsin D were
      detected in estrogen-treated kidneys, 52, 31, and 27 kDa, the major being 52 kDa.
      At 1 and 3 months of estrogen treatment, 52-kDa cathepsin D content increased 1.4
      to 1.6-fold. These changes coincided with a rise in renal estrogen receptor
      levels during the same estrogen treatment periods. More pronounced rises in
      cathepsin D levels, 2.7- and 3.5-fold, were seen after 4 and 5 months of estrogen
      treatment, respectively. A concomitant, 3.0- to 4.0-fold rise in estrogen
      receptor content was also observed. At 5 months of estradiol or DES treatment,
      both 27- and 31-kDa isoforms were present in hamster kidneys, in addition to the
      52-kDa form. Neither progesterone nor DHT treatment affected the untreated levels
      of cathepsin D. Interestingly, either concomitant tamoxifen or DHT and estrogen
      treatment prevented the rise in cathepsin D and estrogen receptor content
      observed after estrogen treatment alone. Primary estrogen-induced renal tumors
      and their metastases exhibited markedly elevated levels of all three isoforms of
      cathepsin D. Immunohistochemical analysis of cathepsin D in kidney sections
      confirmed the Western blot findings. These data suggest a novel role for estrogen
      induced cathepsin D in the hamster kidney during tumorigenesis; that is,
      mediating renal tubular damage as a prelude to reparative cell proliferation,
      thus initiating a multi-step estrogen-driven process which leads to renal tumor
      formation.

PMID- 9230284
TI  - TGF-alpha sustains clonal expansion by promoter-dependent, chemically initiated
      rat hepatocytes.
AB  - A series of promoting and non-promoting barbiturates and hydantoins were examined
      for their ability to sustain the growth of a phenobarbital (PB)-dependent
      hepatocyte line in cell culture. The effective liver tumor promoters,
      pentobarbital, allobarbital and 5-ethyl-5-phenylhydantoin, replaced PB and
      supported 6/27C1 hepatocyte colony formation in vitro at 52-87% of the level
      induced by PB. The weak promoters secobarbital and amobarbital supported colony
      formation at only 11-19% of the PB control. A significant correlation was
      observed for in vivo and in vitro promotion activities of barbiturates and
      hydantoins, indicating that clonal expansion by 6/27C1 hepatocytes was promoter
      dependent. Cell density also appeared to influence hepatocyte growth in vitro.
      Hepatocyte colonies acquired the ability to grow in the absence of PB, such that
      after 10 days incubation with PB, approximately 50% of colonies continued to grow
      in the absence of promoter. This phenomenon of clone-size-dependent hepatocyte
      growth suggested the operation of an autocrine growth factor pathway. Addition of
      the hepatocyte mitogen and autocrine growth factor, transforming growth factor
      alpha (TGF-alpha), to culture medium lacking PB induced a dose-dependent increase
      in 6/27C1 hepatocyte colony formation. At the optimal concentration of 3 ng/ml,
      TGF-alpha sustained hepatocyte clonal expansion at 84% of the level induced by 2
      mM PB. Individual 6/27C1 colonies that grew from single cells in the presence of
      TGF-alpha were tested for promoter-dependent colony formation. Either PB or TGF
      alpha supported colony formation by these cells at similar levels and when
      combined at optimal concentrations, the response appeared to be saturated. When
      these factors were tested in combination at suboptimal concentrations, the two
      compounds were additive for supporting colony formation by the parental 6/27C1
      line. The ability of TGF-alpha to replace PB and sustain hepatocyte clonal
      expansion was confirmed with the tumorigenic 6/15 hepatocyte line. These results
      suggest that TGF-alpha and PB may promote hepatocarcinogenesis by stimulating a
      common signal transduction pathway.

PMID- 9230285
TI  - Iron-induced apoptosis in mouse renal proximal tubules after an injection of a
      renal carcinogen, iron-nitrilotriacetate.
AB  - Redox-active iron was demonstrated in mouse kidney by Timm's sulphide-silver
      staining after an injection of a renal carcinogen, iron-nitrilotriacetate (Fe
      NTA). The iron was on the apical site of tubular epithelia of the renal proximal
      convoluted portion and in the tubules of the straight portion 30 min after the Fe
      NTA injection. As the epithelial cells of the proximal tubules died, the iron
      disappeared in the dead cells and was stored in the cytoplasm of the more distal
      tubular epithelia. Biochemically, redox-active iron in the kidney rapidly
      increased to four times higher than the control 30 min after the Fe-NTA
      injection, then decreased to a plateau which was still higher than the control.
      Iron tightly stored in iron-storage proteins increased gradually by 3 h after the
      injection and then decreased at 5 h. The iron-induced free radical injuries, such
      as lipid peroxidation and protein oxidation, were demonstrated in the renal
      proximal tubules by histochemistry. The nuclei of the proximal tubular epithelia
      shrank and fragmented with the free radical injuries, and were positive for
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling.
      DNA ladder was demonstrated in the mice renal cortexes by agarose gel
      electrophoresis. It was elucidated that redox-active iron caused free radical
      injuries in the proximal tubules of mice kidneys after the injection of a renal
      carcinogenic iron (Fe-NTA) and induced the apoptosis of the proximal tubular
      epithelial cells.

PMID- 9230286
TI  - Orthovanadate, an inhibitor of protein tyrosine phosphatases, acts more potently
      as a promoter than as an initiator in the BALB/3T3 cell transformation.
AB  - The phosphorylation and dephosphorylation of proteins are critical in cellular
      signal transduction. Phorbol esters and okadaic acid, which affect protein
      phosphorylation, are potent promoters in mouse skin carcinogenesis and cell
      transformation in vitro. Orthovanadate inhibits protein tyrosine phosphatases and
      causes hyperphosphorylation of cellular proteins. We have performed two-stage
      transformation assays using BALB/3T3 cells to determine the major activity of
      orthovanadate (1-10 microM) for transformation. This chemical acted as a weak
      initiator because its initiating treatment produced a significant, though small,
      number of transformed foci in the presence of promoting treatment by 12-O
      tetradecanoylphorbol-13-acetate (TPA) but not in the absence of TPA. Promoting
      treatment by orthovanadate markedly enhanced the transformation of the cells
      pretreated by a subthreshold dose of 3-methylcholanthrene (MCA) but not of non
      pretreated cells. Superiority of promoting over initiating activity of
      orthovanadate was confirmed by an assay carried out in the reversed treatment
      sequence (orthovanadate and then MCA), where the transformation frequency was
      conspicuously decreased compared with the regular treatment sequence. The
      transformed foci in the cultures treated by orthovanadate, following MCA
      treatment, continued to grow in normal medium, showing cell proliferation
      independent of orthovanadate. Orthovanadate, in addition to TPA and okadaic acid,
      will be a useful reagent for studying the signaling cascades responsible for
      tumor promotion.

PMID- 9230287
TI  - Epstein-Barr virus episomes as targets for cigarette smoke- and gamma-irradiation
      induced DNA damage: studies on the EBNA-1 region by a new gene-specific
      technique.
AB  - Following our demonstration of cytochrome P450-independent DNA damage induced by
      aqueous solutions of cigarette smoke in human mucosal cells in vivo, and in a
      lymphoblastoid cell line, we have developed a new technique to demonstrate gene
      region specific DNA damage, with the EBNA-1 gene present in multiple nuclear
      matrix-attached episomes in Raji cells serving as an amplified target. DNA was
      extracted from Raji cells treated by gamma-irradiation or aqueous solutions of
      cigarette smoke; adducted bases or other damage were removed chemically by
      depurination/alkali treatment. Single-strand breaks induced directly by cigarette
      smoke as well as DNA cleaved at the site of former adducts were end-labelled
      either with alpha-[32P]dCTP or with biotin-16-dUTP. With 32P-labelling, a dose
      dependent increase in DNA labelling was seen for different concentrations of
      cigarette smoke; undiluted smoke produced a similar amount of damage as 22.4 Gy
      of gamma-irradiation. For isolation of DNA regions that contained biotin label at
      the sites of former damage, DNA was cut by restriction endonucleases and 3-kb
      fragments including the target gene, EBV-EBNA-1, were isolated by agarose-gel
      electrophoresis. Those containing biotin were selected on streptavidin-coated
      magnetic beads. PCR amplification of the bound DNA revealed EBNA-1 DNA only when
      cells were pretreated with either cigarette smoke or gamma-irradiation. The
      presented method thus provides a new approach for detecting gene-specific damage
      in a readily accessible target, EBV episomes. The method is also potentially
      applicable for studying single-copy genes such as p53, the types of adducts
      involved, and quantitative aspects of DNA damage and its repair.

PMID- 9230288
TI  - Detection of DNA damage by Escherichia coli UvrB-binding competition assay is
      limited by the stability of the UvrB-DNA complex.
AB  - To investigate the use of UvrB-binding to detect DNA damage, mobility shift gel
      electrophoresis was used to detect binding of UvrB protein to a 136 bp DNA
      fragment that was randomly adducted with aflatoxin B1 8,9-epoxide and end
      labelled with 32P. After polyacrylamide gel electrophoresis, the shifted band
      that contained DNA bound by UvrB was quantified as a percentage of total
      radioactive substrate DNA. This method was applied to analyse plasmid DNA that
      was adducted with various DNA modifying agents in vitro. These adducts competed
      for UvrB-binding to the labelled substrate. By competing for UvrB-binding with 10
      ng of plasmid DNA that was adducted with known levels of aflatoxin B1, 2-amino-3
      methylimidazo[4,5-f]quinoline, or benzo[a]pyrene diol epoxide, UvrB competition
      could be quantified for DNA adducted with between one adduct in 10(2) and one
      adduct in 10(5) normal nucleotides. However, plasmid DNA exposed to N-methyl-N
      nitrosourea or methylene blue + visible light, did not compete for UvrB-binding,
      even though the presence of UvrABC sensitive sites were confirmed on this DNA by
      a UvrABC incision assay. Mono-adducted 96-bp DNA substrates, which contained an
      internal 32P-label and either a single apurinic site, aflatoxin B1-guanine
      adduct, O6-methylguanine, 8-oxo-deoxyguanosine or non-adducted guanine, were also
      used as substrates for UvrA- and UvrB-binding to examine the stability of UvrB
      DNA complexes with specific adducts. Under similar conditions used for the
      competition assay, significant UvrB-binding was seen only for the aflatoxin
      adducted substrate. These results suggest that stability of UvrB-binding varies
      greatly between bulky and non-bulky adducts. It was also found that rat liver DNA
      from untreated rats inhibited UvrB-binding to the substrate DNA in the
      competition assay, to a degree that was equivalent to competition with plasmid
      adducted at one adduct in 10(3) normal nucleotides.

PMID- 9230289
TI  - Chemopreventive agents-induced regression of azoxymethane-induced aberrant crypt
      foci with the recovery of hexosaminidase activity.

PMID- 9230290
TI  - Enhanced levels in neonatal rat liver of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8
      hydroxydeoxyguanosine), a major mutagenic oxidative DNA lesion.
AB  - The purpose of this study was to determine whether the level of 7,8-dihydro-8-oxo
      2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine) (8-oxo-dG), a major mutagenic DNA
      oxidation product, is enhanced in newborn rat liver DNA as a consequence of
      oxidative stress incurred during the early postnatal period. 32P-postlabeling
      showed this adduct to increase approximately 2-fold from the 20th day of
      gestation (2 days before birth) to a peak level at 50-53 h after birth. Postnatal
      levels exceeded fetal levels at all time points investigated, i.e. 0.5-1, 8, 24,
      50-53, 100, 216 and 432 h after birth. Increased formation of this mutagenic DNA
      lesion during the critical postnatal phase when there is rapid cell proliferation
      in all tissues is proposed to contribute to carcinogenesis in susceptible tissues
      later in life.

PMID- 9230291
TI  - Similar incidence of K-ras mutations in lung carcinomas of FVB/N mice and FVB/N
      mice carrying a mutant p53 transgene.
AB  - Mutated p53 genes are capable of complementing activated ras genes in the
      transformation of primary rat embryo fibroblasts in vitro. Mutations in both
      genes have also been found in several human cancers, including lung carcinomas.
      We generated transgenic mice containing a p53 construct with a missense mutation
      in exon 5 (ala135val) to study the role of p53 mutations in lung tumorigenesis,
      and to facilitate identification of other genetic events that might complement
      p53 mutations in mouse lung carcinogenesis. The p53 transgenic lines exhibited a
      higher frequency of lethal lung tumors than the parental FVB/N strain. We
      examined the spontaneously-arising lung carcinomas from mice expressing the
      mutated p53 transgene for K-ras mutations using single-stranded conformation
      polymorphism (SSCP) and/or direct sequencing approaches. Fifteen of 29 (52%)
      carcinomas contained mutations in the K-ras oncogene. Six of 15 of the K-ras
      mutations were in codon 61 and 9/15 were in codon 12. Subsequent analysis of
      spontaneous lung carcinomas from mice of the FVB/N parental strain showed that
      9/12 (75%) carcinomas examined contained K-ras mutations. Two of these were in
      codon 12, one in codon 13, and 6 were in codon 61. These results demonstrate that
      the frequency of ras mutations does not differ between the p53 FVB/N transgenic
      mice and their parental FVB/N strain but suggest that a high frequency of
      mutations K-ras can be correlated with lung tumorigenesis in both groups of mice.

PMID- 9230292
TI  - Absence of mutations in the transforming growth factor-beta type II receptor in
      sporadic lung cancers with microsatellite instability and rare H-ras1 alleles.
AB  - The transforming growth factor-beta type II receptor (RII) is commonly mutated in
      colon and gastric cancers with microsatellite instability (MI). We utilized our
      series of lung cancers with MI and rare alleles of the H-ras1 gene to determine
      the association between MI and RII mutations and searched the entire RII coding
      region in 33 lung cancers with MI by polymerase chain reaction-single-strand
      conformation polymorphism analysis. We found no mutations, and these data support
      other recent evidence that RII mutations rarely occur except in colon and gastric
      tumors with MI.

PMID- 9230293
TI  - Population-based study of glutathione S-transferase mu gene deletion in adult
      glioma cases and controls.
AB  - Gene deletion at the glutathione S-transferase mu locus (GSTM1) has previously
      been associated with increased risk for environmentally-induced cancers (e.g.
      smoking-related lung cancer). In the present study we examined the hypothesis
      that GSTM1 deletion is a risk factor for malignant brain tumors in adults. We
      compared the prevalence of the GSTM1 homozygous deletion polymorphism in 158
      Caucasian adults with gliomas with 157 controls. Cases and controls were drawn
      from a large population-based case-control study of brain cancers in six San
      Francisco Bay area counties. Overall, the prevalence of the GSTM1 deletion was
      similar in cases (83/158; 53%) and controls (78/157; 50%). Among brain tumor
      cases, analysis of variance modeling indicated a significant interaction of GSTM1
      genotype and gender associated with age at diagnosis (P = 0.02). This effect was
      due to the fact that women with GSTM1 deletion were younger on average at
      diagnosis than women who were GSTM1 positive (43.9 years versus 52.4 years,
      respectively). Age at diagnosis among men was similar for those who were GSTM1
      deleted and GSTM1 positive (49.4 years and 47.2 years, respectively). The younger
      age at diagnosis of GSTM1 null female cases compared with GSTM1 positive cases
      was observed in astrocytoma as well as the higher grade tumors (e.g. glioblastoma
      multiforme). There was no association of GSTM1 deletion with age or gender in
      controls. These studies suggest that among female cases, GSTM1 deletion may be
      associated with earlier age at onset. Confirmation of these findings could
      provide important clues to gene-environment interactions in the etiology of
      malignant brain tumors.

PMID- 9230294
TI  - Re: Barcelo, S., Gardiner, J.M., and Gescher, A. and Chipman, J.K. (1996) CYP2E1
      mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane.
      Carcinogenesis, 17, 277-282.

PMID- 9230295
TI  - Facts and artifacts of ancient DNA.

PMID- 9230296
TI  - Recognition of a transmembrane domain: another role for the ribosome?

PMID- 9230297
TI  - Circadian pacemakers blowing hot and cold--but they're clocks, not thermometers.

PMID- 9230298
TI  - Molecular mechanisms in cell-mediated cytotoxicity.

PMID- 9230299
TI  - Neandertal DNA sequences and the origin of modern humans.
AB  - DNA was extracted from the Neandertal-type specimen found in 1856 in western
      Germany. By sequencing clones from short overlapping PCR products, a hitherto
      unknown mitochondrial (mt) DNA sequence was determined. Multiple controls
      indicate that this sequence is endogenous to the fossil. Sequence comparisons
      with human mtDNA sequences, as well as phylogenetic analyses, show that the
      Neandertal sequence falls outside the variation of modern humans. Furthermore,
      the age of the common ancestor of the Neandertal and modern human mtDNAs is
      estimated to be four times greater than that of the common ancestor of human
      mtDNAs. This suggests that Neandertals went extinct without contributing mtDNA to
      modern humans.

PMID- 9230300
TI  - Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated
      from inside the ribosome during membrane protein integration.
AB  - Portions of the nascent chain are exposed to the lumen, the cytosol, or neither
      at different stages during the cotranslational integration of a protein into the
      ER membrane, as shown by compartment-specific collisional quenching of
      fluorophores incorporated into the polypeptide. The opening or closing of each
      end of the aqueous translocon pore is tightly controlled and occurs in a sequence
      that does not compromise the membrane's permeability barrier. Surprisingly, these
      structural changes at the membrane are effected by the transmembrane segment in
      the nascent protein from inside the ribosome. Thus, the ribosome, not the
      translocon, first recognizes the transmembrane segment and triggers long-range
      structural changes at the translocon that may be involved in shifting its
      function from translocation to integration.

PMID- 9230301
TI  - A small, stable RNA induced by oxidative stress: role as a pleiotropic regulator
      and antimutator.
AB  - Exposure of E. coli to hydrogen peroxide induces the transcription of a small RNA
      denoted oxyS. The oxyS RNA is stable, abundant, and does not encode a protein.
      oxyS activates and represses the expression of numerous genes in E. coli, and
      eight targets, including genes encoding the transcriptional regulators FhlA and
      sigma(S), were identified. oxyS expression also leads to a reduction in
      spontaneous and chemically-induced mutagenesis. Our results suggest that the oxyS
      RNA acts as a regulator that integrates adaptation to hydrogen peroxide with
      other cellular stress responses and helps to protect cells against oxidative
      damage.

PMID- 9230302
TI  - A proteinaceous gene regulatory thermometer in Salmonella.
AB  - Novel utilization of the coiled-coil motif is presented that enables TlpA, an
      autoregulatory repressor protein in Salmonella, to sense temperature shifts
      directly and thereby to modulate the extent of transcription repression.
      Salmonella cells shifted to higher temperatures, such as those encountered at
      host entry, showed derepressed tlpA activity. tlpA::lacZ fusions indicated that
      the promoter itself is insensitive to thermal shifts and that transcription
      control was exerted by the autorepressor TlpA only. In vitro studies with highly
      purified TlpA showed concentration and temperature dependence for both fully
      folded conformation and function, indicating that the thermosensing in TlpA is
      based on monomer-to-coiled-coil equilibrium.

PMID- 9230303
TI  - Identification and structural characterization of the ATP/ADP-binding site in the
      Hsp90 molecular chaperone.
AB  - Hsp90 molecular chaperones in eukaryotic cells play essential roles in the
      folding and activation of a range of client proteins involved in cell cycle
      regulation, steroid hormone responsiveness, and signal transduction. The
      biochemical mechanism of Hsp90 is poorly understood, and the involvement of ATP
      in particular is controversial. Crystal structures of complexes between the N
      terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a
      specific adenine nucleotide binding site homologous to the ATP-binding site of
      DNA gyrase B. This site is the same as that identified for the antitumor agent
      geldanamycin, suggesting that geldanamycin acts by blocking the binding of
      nucleotides to Hsp90 and not the binding of incompletely folded client
      polypeptides as previously suggested. These results finally resolve the question
      of the direct involvement of ATP in Hsp90 function.

PMID- 9230304
TI  - The translocating RecBCD enzyme stimulates recombination by directing RecA
      protein onto ssDNA in a chi-regulated manner.
AB  - Double-stranded DNA break repair and homologous recombination in E. coli are
      initiated by the RecBCD enzyme, which unwinds and simultaneously degrades DNA
      from a double-stranded DNA end. This process is stimulated by cis-acting DNA
      elements, known as chi sites. Using both in vitro pairing and nuclease protection
      assays, we demonstrate that the translocating RecBCD enzyme, which has been
      activated by chi, coordinates the preferential loading of the homologous pairing
      protein, RecA, onto the resultant single-stranded DNA downstream of chi. This
      facilitated loading of RecA protein results in a substantial increase in both the
      efficiency and rate of in vitro recombination reactions and offers an explanation
      for stimulation of recombination and repair in vivo by chi.

PMID- 9230305
TI  - Holliday junctions accumulate in replication mutants via a RecA homolog
      independent mechanism.
AB  - The Holliday junction recombination intermediate, an X-shaped DNA molecule
      (xDNA), was analyzed at rDNA in mitotically growing yeast. In wild-type cells,
      xDNA is only detected at S phase, suggesting that recombination is stimulated to
      repair replication-related lesions. A search for mutations that increase the
      level of xDNA uncovered a gene encoding a subunit of DNA polymerase alpha.
      Systematic examination of replication mutants revealed that defects in polymerase
      alpha and delta but not the epsilon complex stimulate the level of xDNA. These
      xDNAs are Holliday junctions and not replication intermediates. The level of
      Holliday junctions is greatly reduced in rad52 mutants, but surprisingly, not in
      mutants defective in the three known mitotically expressed yeast RecA homologs.

PMID- 9230306
TI  - Stimulation of RAR alpha activation function AF-1 through binding to the general
      transcription factor TFIIH and phosphorylation by CDK7.
AB  - The activity of the N-terminal activation function AF-1 of RAR alpha1 is
      abrogated upon mutation of a phosphorylatable serine residue (Ser-77).
      Recombinant RAR alpha was phosphorylated by a variety of proline-directed protein
      kinases in vitro. However, only the coexpression of cdk7 stimulated Ser-77
      phosphorylation in vivo and enhanced transactivation by RAR alpha, but not by a
      S77A RAR mutant. Both free CAK (cdk7, cyclin H, MAT1) and the CAK-containing
      general transcription factor TFIIH phosphorylated Ser-77 in vitro. Furthermore
      RAR alpha bound free CAK and purified TFIIH in vitro, and RAR alpha-TFIIH
      complexes could be isolated from HeLa nuclear extracts. These findings represent
      the first example of activation of a transactivator through binding to and
      phosphorylation by a general transcription factor.

PMID- 9230307
TI  - FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor
      GATA-1 in erythroid and megakaryocytic differentiation.
AB  - The hematopoietic transcription factor GATA-1 is essential for development of the
      erythroid and megakaryocytic lineages. Using the conserved zinc finger DNA
      binding domain of GATA-1 in the yeast two-hybrid system, we have identified a
      novel, multitype zinc finger protein, Friend of GATA-1 (FOG), which binds GATA-1
      but not a functionally inactive mutant lacking the amino (N) finger. FOG is
      coexpressed with GATA-1 during embryonic development and in erythroid and
      megakaryocytic cells. Furthermore, FOG and GATA-1 synergistically activate
      transcription from a hematopoietic-specific regulatory region and cooperate
      during both erythroid and megakaryocytic cell differentiation. These findings
      indicate that FOG acts as a cofactor for GATA-1 and provide a paradigm for the
      regulation of cell type-specific gene expression by GATA transcription factors.

PMID- 9230308
TI  - Developmentally regulated mitochondrial fusion mediated by a conserved, novel,
      predicted GTPase.
AB  - The Drosophila melanogaster fuzzy onions (fzo) gene encodes the first known
      protein mediator of mitochondrial fusion. During Drosophila spermatogenesis,
      mitochondria in early postmeiotic spermatids aggregate, fuse, and elongate beside
      the growing flagellar axoneme. fzo mutant males are defective in this
      developmentally regulated mitochondrial fusion and are sterile. fzo encodes a
      large, novel, predicted transmembrane GTPase that becomes detectable on spermatid
      mitochondria late in meiosis II, just prior to fusion, and disappears soon after
      fusion is complete. Missense mutations that alter conserved residues required for
      GTP binding in other GTPases inhibit the fusogenic activity of Fzo in vivo but do
      not affect its localization. Fzo has homologs of unknown function in mammals,
      nematodes, and yeast.

PMID- 9230309
TI  - Mis6, a fission yeast inner centromere protein, acts during G1/S and forms
      specialized chromatin required for equal segregation.
AB  - Disorder in sister chromatid separation can lead to genome instability and
      cancer. A temperature-sensitive S. pombe mis6-302 frequently loses a
      minichromosome at 26 degrees C and abolishes equal segregation of regular
      chromosomes at 36 degrees C. The mis6+ gene is essential for viability, and its
      deletion results in missegregation identical to mis6-302. Mis6 acts before or at
      the onset of S phase, and mitotic missegregation defects are produced only after
      the passage of G1/S at 36 degrees C. Mis6 locates at the centromeres throughout
      the cell cycle. In the mutant, positioning of the centromeres becomes abnormal,
      and specialized chromatin in the inner centromeres, which give the smear
      micrococcal nuclease pattern in wild type, is disrupted. The ability to establish
      correct biorientation of sister centromeres in metaphase cells requires the Mis6
      containing chromatin and originates during the passage of G1/S.

PMID- 9230310
TI  - ACF, an ISWI-containing and ATP-utilizing chromatin assembly and remodeling
      factor.
AB  - We describe the purification and characterization of ACF, an ATP-utilizing
      chromatin assembly and remodeling factor. ACF is a multisubunit factor that
      contains ISWI protein and is distinct from NURF, another ISWI-containing factor.
      In chromatin assembly, purified ACF and a core histone chaperone (such as NAP-1
      or CAF-1) are sufficient for the ATP-dependent formation of periodic nucleosome
      arrays. In chromatin remodeling, ACF is able to modulate the internucleosomal
      spacing of chromatin by an ATP-dependent mechanism. Moreover, ACF can mediate
      promoter-specific nucleosome reconfiguration by Gal4-VP16 in an ATP-dependent
      manner. These results suggest that ACF acts catalytically both in chromatin
      assembly and in the remodeling of nucleosomes that occurs during transcriptional
      activation.

PMID- 9230311
TI  - Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an
      alternate pathway in oligosaccharide biosynthesis.
AB  - Alpha-mannosidase-II (alphaM-II) catalyzes the first committed step in the
      biosynthesis of complex asparagine-linked (N-linked) oligosaccharides (N
      glycans). Genetic deficiency of alphaM-II should abolish complex N-glycan
      production as reportedly does inhibition of alphaM-II by swainsonine. We find
      that mice lacking a functional alphaM-II gene develop a dyserythropoietic anemia
      concurrent with loss of erythrocyte complex N-glycans. Unexpectedly, nonerythroid
      cell types continued to produce complex N-glycans by an alternate pathway
      comprising a distinct alpha-mannosidase. These studies reveal cell-type-specific
      variations in N-linked oligosaccharide biosynthesis and an essential role for
      alphaM-II in the formation of erythroid complex N-glycans. alphaM-II deficiency
      elicits a phenotype in mice that correlates with human congenital
      dyserythropoietic anemia type II.

PMID- 9230313
TI  - The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway
      that regulates embryonic axis formation.
AB  - Mutations at the mouse Fused locus have pleiotropic developmental effects,
      including the formation of axial duplications in homozygous embryos. The product
      of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein
      Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial
      duplications disrupt the major mRNA, suggesting that Axin negatively regulates
      the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus
      embryos inhibits dorsal axis formation by interfering with signaling through the
      Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS
      domain induces an ectopic axis, apparently through a dominant-negative mechanism.
      Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in
      embryonic axis formation in mammals and amphibians.

PMID- 9230312
TI  - Pax6 controls progenitor cell identity and neuronal fate in response to graded
      Shh signaling.
AB  - Distinct classes of motor neurons and ventral interneurons are generated by the
      graded signaling activity of Sonic hedgehog (Shh). Shh controls neuronal fate by
      establishing different progenitor cell populations in the ventral neural tube
      that are defined by the expression of Pax6 and Nkx2.2. Pax6 establishes distinct
      ventral progenitor cell populations and controls the identity of motor neurons
      and ventral interneurons, mediating graded Shh signaling in the ventral spinal
      cord and hindbrain.

PMID- 9230314
TI  - Clarity of judgment during amoral times in a society addicted to codified law.
      Neel Distinguished Research Lecturer.

PMID- 9230315
TI  - Medical ethics in today's society.

PMID- 9230316
TI  - Effect of sinus surgery on quality of life.
AB  - Although sinus surgery may reduce the incidence of recurrent infection in
      patients with chronic sinusitis, little is known about the effect of such surgery
      on a patient's quality of life. One hundred eight patients undergoing ethmoid
      sinus surgery were prospectively evaluated with statistically validated measures
      of sinusitis-specific and general health-related quality of life. Twelve months
      after surgery significant improvements were found in sinus-specific health
      status, including a reduction in symptoms (p < 0.001) and medication usage (p <
      0.001). An overall improvement was found in 82% of patients, whereas 11% were
      worse, and 7% remained unchanged. Measures of general health status demonstrated
      preoperative decrements in five of eight subscales as compared with the normal
      population. Six months after surgery significant improvements were noted in six
      categories (p < 0.05), and most attained near-normative levels. Individuals with
      asthma demonstrated greater overall improvement in general health status than did
      other cohorts (p < 0.05). We conclude that patients with chronic sinusitis
      achieve large improvements in sinusitis-specific quality-of-life measures 12
      months after sinus surgery, as well as improvements in general health status.

PMID- 9230317
TI  - Mucoceles of the maxillary sinus.
AB  - The maxillary sinus is an uncommon site for mucoceles within the paranasal
      sinuses. In this study nine patients with maxillary sinus mucoceles are
      presented. Six of these patients were treated by open approaches, and three were
      treated by endoscopic drainage alone. For uncomplicated maxillary sinus
      mucoceles, endoscopic drainage appears to be a reasonable approach, whereas for
      more complicated cases extending outside the sinus, open approaches may be
      required.

PMID- 9230318
TI  - Evaluation of the nasal cavity by acoustic rhinometry in normal and allergic
      subjects.
AB  - With acoustic rhinometry, one can detect a difference in response to a topical
      decongestant between normal and allergic subjects at the minimal cross-sectional
      area. The minimal cross-sectional area corresponds in most cases to the anterior
      end of the inferior turbinate or the first valley, which occurs after the nose
      piece of the acoustic rhinometer on the acoustic rhinometry graph. Allergic
      patients typically have an increase in nasal mucosal swelling, which leads to a
      decrease in the nasal volume and area and, subsequently, to an increase in
      congestion. In this study acoustic rhinometry was used to test normal and
      allergic subjects before and after the application of a topical decongestant (1%
      phenylephrine (Neo-Synephrine)). Symptoms were measured by a five-point scale.
      Results showed that increasing symptom scores demonstrated a trend toward being
      related to decreasing area as measured at the minimal cross-sectional area or
      nasal valve. The average total percent change at the minimal cross-sectional area
      was calculated for both groups and compared. The normal subjects had an average
      total percent area change at the minimal cross-sectional area of 15.6% +/- 14.8%,
      and the allergic subjects had a percent change of 24.6% +/- 20.8%. This
      represents a significant difference between the normal and allergic subjects in
      response to the topical decongestant at the minimal cross-sectional area (p =
      0.04). However, the average total percent change was not significantly different
      between the two groups at the second and third valleys. At the second valley, the
      normal subjects had a percent change of 40% +/- 17.5%, and the allergic subjects
      had a percent change of 36% +/- 18.5%. At the third valley, the normal subjects
      had a percent change of 35% +/- 15.4%, and the allergic subjects had a percent
      change of 32% +/- 20.6% (p = 0.4 and 0.5, respectively). The total area was
      calculated by adding measurements from both right and left nasal cavities for
      each subject in an attempt to control the effect of the nasal cycle. Acoustic
      rhinometry makes it possible to detect a trend in the relationship between either
      a decrease in area at the minimal cross-sectional area or a decrease in the total
      volume from 0 to 7 cm into the nasal cavity and congestion. A statistically
      significant difference between normal and allergic subjects in their response to
      a topical decongestant at the minimal cross-sectional area was detected by
      acoustic rhinometry at the nasal valve.

PMID- 9230319
TI  - Endoscopic treatment of allergic fungal sinusitis.
AB  - Fungal sinusitis has been seen increasingly in immunocompetent individuals. The
      literature has stressed the importance of diagnosing these cases. Surgical
      debridement is the treatment of choice. Six immunocompetent individuals with
      allergic fungal sinusitis were seen at West Virginia University between January
      1992 and December 1993. After adequate evaluation, endoscopic surgical
      debridement was performed. After surgery they were treated with systemic or
      topical steroids and oral antibiotics for several weeks. Two patients required a
      second procedure within a year. Four of our six patients had positive fungal
      cultures for Aspergillus or Curvularia. None of our patients had evidence of
      invasive disease on histopathology, and systemic antifungal therapy was not
      required. Patient course and response will be discussed in detail along with a
      brief review of allergic fungal sinusitis.

PMID- 9230320
TI  - Prognosis for allergic fungal sinusitis.
AB  - Allergic fungal sinusitis is a recently described clinical entity that has gained
      increased attention as a cause of chronic sinusitis. The diagnosis can be
      established by demonstrating (1) type I hypersensitivity confirmed by history,
      skin tests, or serology; (2) nasal polyposis; (3) characteristic CT scan; (4)
      eosinophilic mucus without fungal invasion into sinus tissue; and (5) positive
      fungal stain of sinus contents removed intraoperatively or during office
      endoscopy. The exact pathogenesis of allergic fungal sinusitis remains
      controversial, and no treatment modality has proved to be consistently effective.
      Several reports during the last decade have suggested that allergic fungal
      sinusitis recurs more frequently than chronic bacterial sinusitis, but no studies
      have specifically addressed the prognosis of allergic fungal sinusitis. During
      the past two and a half years, we have treated 26 patients with allergic fungal
      sinusitis. The treatment always included functional endoscopic sinus surgery,
      topical nasal steroids, postoperative nasal saline irrigations, and endoscopic
      cleaning in the office. Adjuvant medical therapy included systemic steroids, oral
      antifungals, a combination of systemic steroids and oral antifungals, or in some
      cases, no additional treatment. Outcome was graded subjectively as improved,
      unchanged, or worse. Mean follow-up was 14.5 months. Twenty-two of 26 patients
      were improved. In reviewing postoperative outcomes, we observed endoscopic
      recurrent disease that generally preceded patient symptoms. Consequently, we
      developed an endoscopic staging system to record postoperative clinical status.
      Use of this staging system allowed evaluation of various treatments and enabled
      classification of patient outcome. Nineteen of 24 patients examined with
      extensive follow-up had objective signs of recurrent disease. It appears that
      this is a chronic disease characterized by physical signs that appear before the
      return of subjective clinical symptoms.

PMID- 9230321
TI  - Eosinophil cationic protein in mucosal biopsies from patients with allergy and
      otitis media with effusion.
AB  - Nine patients with persistent middle ear effusion and allergy confirmed by skin
      testing were evaluated for eosinophils by histochemical staining of middle ear
      mucosal biopsy specimens for eosinophil cationic protein. The study was designed
      to determine whether eosinophils were present in the middle ear mucosa of these
      patients and whether the elevated levels of eosinophil cationic protein reported
      in effusion from patients with chronic otitis media with effusion and allergy
      might originate within the mucosa itself. Seven of nine patients with otitis
      media with effusion had eosinophil cationic protein containing eosinophils (12 to
      15 per high-power field) and degranulated eosinophil cationic protein material in
      the stroma of their mucosal biopsy specimens. Positive and negative biopsy
      findings correlated directly with respective high and low effusion levels of
      eosinophil cationic protein (p = 0.03), reflecting an intrinsic immune-mediated
      process occurring within the middle ear mucosa.

PMID- 9230322
TI  - Epistaxis: a retrospective review of hospitalized patients.
AB  - A 2-year retrospective study (August 1, 1992, to July 31, 1994) reviews medical
      records of 249 hospitalized epistaxis patients at seven Baltimore-area hospitals.
      This review represents the first multihospital study of patients hospitalized
      with epistaxis. The study evaluates multiple factors associated with epistaxis:
      demographics, underlying medical diseases, use of anticoagulation medication,
      site of epistaxis, and month of hospital admission. Blood transfusion
      requirement, hematocrit level, length of stay, treatment, and local/systemic
      complications are studied as well. The month of hospital admission was evenly
      distributed without a wintertime predominance, and the mean length of stay was 4
      days. Treatment and outcome were similar in all hospitals, and more than 83% of
      patients responded to packing, balloon placement, local cautery, or a combination
      thereof. Of the 249 patients reviewed, 30 underwent surgical endoscopic cautery,
      3 required formal surgical arterial ligation, and 1 underwent arterial
      embolization. All 30 endoscopic cauterizations successfully stopped the
      epistaxis, and this technique proved to be a useful adjunct for patients who
      required multiple interventions. The review identified a 3% complication rate of
      epistaxis and its treatment, including synechiae, aspiration, angina, myocardial
      infarction, and hypovolemia. No deaths were directly attributable to epistaxis or
      its treatment.

PMID- 9230323
TI  - The screening RAST: is it a valid concept?
AB  - Dr. William King in 1982 advocated the use of a "miniscreen" panel of six
      antigens to cost-effectively initiate allergy testing. In a study of 100
      consecutive patients, we found that a "midiscreen" of nine antigens was more
      sensitive and efficient and more accurately identified negative responders.
      However, the miniscreen was also effective if adjusted for regional antigen
      differences.

PMID- 9230324
TI  - Cardiopulmonary compromise after use of topical and submucosal alpha-agonists:
      possible added complication by the use of beta-blocker therapy.
AB  - We report the specifics of 12 cases of severe hypertension after the
      intraoperative use of topical phenylephrine, submucosal epinephrine, or both. Ten
      of these 12 patients also developed severe pulmonary edema. Seven of the twelve
      were treated with beta blockers; 3 of whom suffered cardiac arrest. We propose a
      common mechanism: the vasoconstrictors caused systemic hypertension, increased
      left ventricular afterload, decreased left ventricular compliance, and decreased
      cardiac output. In those patients treated with beta blockers, decreased
      contractility and inability to increase heart rate further compromised
      cardiopulmonary function.

PMID- 9230325
TI  - Negative-pressure pulmonary edema in the otolaryngology patient.
AB  - It is estimated that 11% of all patients requiring active intervention for acute
      upper airway obstruction develop negative-pressure pulmonary edema. This
      pathologic process typically has a benign and rapidly resolving clinical course
      with the prompt use of mechanical ventilation and positive end expiratory
      pressure. A review of the literature, however, has revealed a morbidity and
      mortality rate of 11% to 40% in reported series. During the years 1991 through
      1993, six patients were identified in whom negative-pressure pulmonary edema
      developed after various otolaryngologic procedures. Five (84%) of the six
      patients had complete resolution of the pulmonary edema within 24 hours, and the
      sixth patient progressed to prolonged mechanical ventilation and eventual death.
      In an effort to further understand the pathophysiology of this disease, a cardiac
      evaluation was performed by use of echocardiography on all six patients. In three
      of the six patients, studies revealed an underlying cardiac anomaly not
      previously identified by history or physical examination. Findings included one
      case of hypertrophic cardiomyopathy and two cases of pulmonary and tricuspid
      valvular insufficiency. This 50% incidence of cardiac anomalies is striking, in
      contrast to the less than 1% incidence of these anomalies in the general adult
      population. To our knowledge, this is the first study to implicate an underlying
      cardiac cause for the generation of negative-pressure pulmonary edema. On the
      basis of this study, we recommend that echocardiography be a part of the routine
      evaluation of all patients who manifest negative-pressure pulmonary edema.

PMID- 9230326
TI  - Current perspective on temporal bone trauma.
AB  - The improved survival of patients sustaining massive head injuries has increased
      the number of temporal bone fractures being managed by otolaryngologists and
      neurosurgeons. We performed a prospective analysis of 35 patients with head
      injury with temporal bone trauma. The major emphasis of this study was to
      investigate the incidence, management, and outcome of facial nerve injury in such
      patients and to evaluate the importance of electrodiagnostics in the surgical
      management of the facial nerve. The results of this study indicate an incidence
      of fracture type, hearing loss, and facial nerve paralysis similar to that
      already recorded in the literature. This study underscores the importance of
      evoked electromyography, or electroneuronography, in assessing facial nerve
      function. Electroneuronography provided the indications for surgical intervention
      for facial paralysis. All patients having surgery for facial paralysis as
      determined by electroneuronographic findings had pathology of the facial nerve.

PMID- 9230327
TI  - Factors predictive of poor compliance with follow-up care after facial trauma: a
      prospective study.
AB  - We performed a prospective study of 59 consecutive patients with facial trauma
      who were treated at an urban public hospital. We obtained demographic and
      clinical data before treatment, then recorded compliance with clinic follow-up
      care. As expected, young, minority male patients, victims of assault, and blunt
      mechanisms of injury predominated in our series, and midface fractures and soft
      tissue injuries were most commonly seen. Thirty-one (52%) patients were admitted,
      and 28 (48%) were treated as outpatients. Although 66% of patients kept their
      initial follow-up appointment, only 46% of patients were seen to completion of
      the follow-up period. We used univariate and multivariate analyses to identify
      factors predictive of poor compliance with follow-up care. Factors predictive of
      poor compliance with the initial follow-up appointment identified in the
      multivariate analysis were orbital injury site (p < 0.001), Caucasian race (p =
      0.007), and not having a telephone at home (p = 0.043). Factors predictive of
      poor compliance with completion of follow-up were failure to keep initial
      appointment (p < 0.001), and treatment with observation, suture only, or open
      reduction internal fixation only (p = 0.018). Age, marital status, employment
      status, education level, and hospital admission of the patient were not
      predictive of compliance with follow-up care. Because compliance with follow-up
      care may be poor, patients with facial trauma should be managed aggressively
      initially. In particular, patients with orbital fractures, and those treated with
      watchful waiting only may have poorer long-term compliance with follow-up care.

PMID- 9230329
TI  - Multicenter study of the efficacy and safety of oral ciprofloxacin in the
      treatment of chronic suppurative otitis media in adults. The French Study Group.
AB  - Chronic suppurative otitis media is a common and potentially dangerous clinical
      condition that is difficult to treat because the most common infecting organisms
      are often resistant to many antibiotics. Recently, fluoroquinolones such as
      ciprofloxacin have provided a new therapeutic possibility, offering a wide range
      of antibacterial activity and proven concentration in the middle ear. Therefore
      in the current study, we assessed the efficacy and safety of oral ciprofloxacin
      (500 mg twice daily for 10 days) in the treatment of suppurative chronic otitis
      media in adults. One hundred sixty-four patients were enrolled during a 3-month
      period by 49 ear, nose, and throat physicians in general practice. The mean
      duration of symptoms was 158 months, with the acute exacerbation lasting 72.5
      days. Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis were
      most commonly isolated. At the end of treatment, the otorrhea had disappeared in
      104 of the 155 (67.1%) evaluated patients. The bacteriologic eradication rate was
      64.5%. After 4 weeks of follow-up care, 93.2% of patients had no recurrence of
      infection. In 4 patients, treatment was discontinued prematurely after an adverse
      event. We conclude that ciprofloxacin is an effective and well-tolerated general
      practice treatment for suppurative chronic otitis media in adults.

PMID- 9230328
TI  - A comparison of ibuprofen versus acetaminophen with codeine in the young
      tonsillectomy patient.
AB  - OBJECTIVE: To compare the use of ibuprofen with the use of acetaminophen with
      codeine for posttonsillectomy management. BACKGROUND: We were not satisfied with
      our traditional pain-management practice for tonsillectomy patients. We hoped to
      find a new approach for improved patient comfort and avoid scheduled, abusable
      drugs such as codeine. DESIGN: Intervention, prospective, randomized control
      trial. Follow-up was 1 month. SETTING: University referral center; institutional
      pediatric practice, ambulatory. PATIENTS: 110 children undergoing tonsillectomy
      with or without other procedures. Consecutive patients were offered
      participation. Enrollees were randomly assigned to one of two classes and
      analyzed with the initial assignment. No patients withdrew for adverse effects,
      although 12 in group 2 used codeine and 5 of those used acetaminophen, whereas 2
      in group 1 received ibuprofen. INTERVENTIONS: Patients received either
      acetaminophen with codeine (group 1) or ibuprofen (group 2) for postoperative
      pain control. MAIN OUTCOME MEASURES: The main outcomes, determined before
      initiation of the study, were assessment of (1) postoperative bleeding, (2) pain,
      (3) efficacy of relief of pain by drug, (4) nausea, (5) emesis, (6) readmission
      to hospital, (7) average temperature, and (8) highest temperature after surgery.
      RESULTS: The only statistically significant difference is less nausea in patients
      receiving ibuprofen (p = 0.0049). Of note, no difference existed in postoperative
      bleeding, pain, or temperature control. CONCLUSIONS: Ibuprofen is at least as
      effective as acetaminophen with codeine for postoperative pain control in
      children after tonsillectomy.

PMID- 9230330
TI  - Postoperative hypertension after radical neck dissection.
AB  - Postoperative hypertension after radical neck dissection was detected in 20.2% of
      109 neck dissections in our department between 1989 and 1993. It was probably
      caused by carotid sinus denervation and appeared after the vasodilation generated
      by anesthesia had subsided. If postoperative hypertension was encountered after
      the first operation, the risk of such hypertension after surgery on the
      contralateral side significantly increased.

PMID- 9230331
TI  - The use of lidocaine in microvascular reconstruction.
AB  - Vasospasm is known to have an adverse effect on the survival of free tissue
      transfers. Prolonged vasoconstriction decreases blood flow to the flap and
      promotes thrombosis at the anastomotic site. Because of its wide availability and
      rapid effect, topically applied lidocaine is used by many surgeons to prevent and
      correct vasospasm. Mucosal absorption of lidocaine is known to be rapid.
      Absorption by the surgical bed during microvascular reconstruction has not
      previously been determined. We had three specific aims: (1) to determine whether
      systemic absorption occurs, (2) if so, to determine the degree of absorption, and
      (3) to determine whether the type of reconstruction affects the degree of
      absorption. Twelve consecutive patients were entered into the study, four in a
      myocutaneous reconstructive group and eight in a fasciocutaneous group. Baseline
      serum lidocaine levels were drawn. After the initial application of lidocaine,
      levels were drawn every 30 minutes. Final levels were drawn 120 minutes after the
      last application. The total amount of lidocaine used ranged from 720 mg to 2600
      mg. Application ranged from 7.5 mg/minute to 34.7 mg/minute (2 to 9 times the
      estimated toxic dose of 4 mg/minute for a patient weighing 70 kg). Results ranged
      from undetectable (<0.5 microg/ml) to minimal therapeutic levels (1.6 microg/ml).
      Toxic levels (>6.0 microg/ml) were not encountered. Significant (p < 0.05)
      differences were found between the fasciocutaneous group, which generally had no
      detectable serum levels, and the myocutaneous group, which had detectable
      subtherapeutic to minimally therapeutic levels. Doses considered toxic by
      intravenous or mucous membrane application may safely be applied topically.
      Greater absorption was found in the myocutaneous group, which is believed to be a
      result of the richer absorption surface provided by the muscular tissue.

PMID- 9230332
TI  - Treatment of massive or life-threatening hemangiomas with recombinant alpha(2a)
      interferon.
AB  - OBJECTIVE: To assess the response of massive, life-threatening, or function
      impairing hemangiomas in pediatric patients receiving daily alpha(2a)-interferon
      subcutaneously. METHODS: The effect of 3 or more months of subcutaneous alpha(2a)
      interferon (3 mU/m2) was prospectively evaluated in 10 patients with hemangiomas
      necessitating medical intervention. Hemangioma characteristics and extent were
      initially assessed by radiographic imaging in all but one patient. alpha(2a)
      Interferon tolerance was monitored, and reduction in hemangioma size was recorded
      as marked (>50%), moderate (25% to 50%), or minimal (<25%). RESULTS: Hemangiomas
      were apparent at birth in 8 of 10 patients, and alpha(2a)-interferon was
      initiated at a median age of 4.5 months. Symptoms necessitating therapeutic
      intervention included congestive heart failure, airway obstruction, dysphagia,
      infection, failure to thrive, external auditory canal occlusion, visual axis
      impairment, and severe facial deformity. Four patients received treatment before
      referral that included systemic steroids (n = 2), intralesional steroids (n = 1),
      or surgical/laser excision (n = 2). alpha(2a)-Interferon therapy was well
      tolerated. Most patients had a temporary elevation in body temperature during the
      first month of therapy. One patient with anorexia required nasogastric feedings
      and a temporary reduction in her alpha(2a)-interferon dose. An additional patient
      with irritability was withdrawn from the study at his parents' request even
      though this symptom persisted after drug cessation. Hemangioma response to
      alpha(2a)-interferon was marked in six patients, moderate in two, and minimal in
      one whose lesion had features suggestive of a vascular malformation. Early signs
      of involution were usually evident within 6 weeks and often heralded by cutaneous
      blanching. alpha(2a)-interferon therapy was concluded in four patients after a
      mean duration of 20 months. CONCLUSIONS: Daily subcutaneous alpha(2a)-interferon
      is well tolerated in pediatric patients and appears effective in hastening
      involution of symptomatic hemangiomas. A significant response is unlikely in
      lesions with features suggestive of a vascular malformation.

PMID- 9230333
TI  - Perioperative strategies in the management of carotid body tumors.
AB  - Despite the availability of noninvasive neuroradiographic techniques for the
      evaluation of head and neck neoplasms, paragangliomas of the carotid body often
      achieve substantial size before definitive diagnosis. Surgical "exploration" for
      the attempted resection of these lesions often results in significant blood loss,
      inadvertent cranial nerve injury, and procedure abandonment with partial tumor
      removal. Sixteen carotid body tumors were surgically resected at our institution
      between July 1988 and January 1995. Four of these patients had undergone
      cytologic examination by fine-needle aspiration (FNA) and another 6 patients
      underwent failed attempted resection of their lesions as the result of
      intraoperative hemorrhage. Of the remaining 6 patients referred for the first
      time evaluation of a "neck mass," the diagnosis was made by patient history,
      physical examination, magnetic resonance imaging, or magnetic resonance
      angiography. Complete tumor removal was accomplished in all 16 patients using a
      variety of lateral transcervical and skull base approaches. This article focuses
      on the clinicoradiographic diagnosis of carotid body tumors that do not need
      preoperative histologic confirmation. Specific intraoperative techniques for
      tumor removal, carotid artery management, and cranial nerve preservation are
      demonstrated through case presentations. Perioperative morbidity and overall
      results are detailed for this series of patients.

PMID- 9230334
TI  - Low-grade adenocarcinoma of nasal passages.

PMID- 9230335
TI  - Fine-needle aspiration: clinical pearls.

PMID- 9230336
TI  - Subcutaneous and retropharyngeal emphysema after dental procedures.

PMID- 9230337
TI  - Arteriovenous fistula after temporomandibular joint arthroscopy treated with
      external carotid embolization.

PMID- 9230338
TI  - Minimal access surgery of the frontonasal duct through a simultaneous
      transfrontal and intranasal approach.

PMID- 9230339
TI  - Middle cranial fossa surgery with image-guided instrumentation.

PMID- 9230340
TI  - New safety skin hooks.

PMID- 9230341
TI  - Endoscopic appearance of laryngeal atresia.

PMID- 9230342
TI  - Angiosarcoma of the scalp.

PMID- 9230343
TI  - Pulmonary metastasis to the nasal tip.

PMID- 9230344
TI  - GLUT1 is adequate for glucose uptake in GLUT2-deficient insulin-releasing beta
      cells.
AB  - GLUT2 may play an important role in pancreatic beta-cell glucose metabolism. A
      decrease in glucose uptake due to underexpression of GLUT2 has been considered as
      the cause of beta-cell dysfunction in diabetes with different pathogenesis.
      However, this view has been challenged by recent studies, in which the
      underexpression of GLUT2 was not accompanied by a decrease in glucose uptake. Our
      present aim is to evaluate the presumed importance of GLUT2 in maintaining the
      efficiency of beta-cell glucose uptake. We studied the kinetic characteristics of
      3-O-methylglucose uptake in two beta-cell lines. One of these is the beta TC3
      cell line which expresses GLUT1 and the other is the beta HC9 cell line which
      expresses both GLUT1 and GLUT2. Under equilibrium exchange conditions, 3-O
      methylglucose transport in these two cell lines showed similar values of K(m) and
      V(max). The apparent IC50 of cytochalasin B for inhibiting 3-O-methylglucose
      transport in beta HC9 cells was nine times as high as in beta TC3 cells,
      indicating that GLUT1 is the critically important glucose transporter in the beta
      TC3 cell line and GLUT2 in the beta HC9 cell line. In both cell lines, the rates
      of glucose uptake were at least three times as fast as that of glucose
      phosphorylation. Our results suggest that GLUT1 is able to compensate for GLUT2
      loss as it occurs in beta TC3 and maintains a commensurately high capacity of
      glucose uptake to sustain glucose metabolism in pancreatic beta-cells.

PMID- 9230346
TI  - Regulation of islet growth: reports from the Second Seattle Islet Symposium.

PMID- 9230345
TI  - Metformin does not alter diabetes incidence in the NOD mouse.
AB  - In insulin-dependent (type 1) diabetes mellitus, increasing peripheral insulin
      sensitivity might be a useful approach in controlling the process leading to beta
      cell destruction by reducing insulin output and thereby reducing the antigenicity
      associated with its release. The aim of this study was to investigate whether the
      use of a biguanide, Metformin, which has been suggested to increase insulin
      sensitivity, was capable of modifying the natural history of diabetes in a model
      of type 1 diabetes, the non-obese diabetic (NOD) mouse. Using age-, sex- and
      litter-matched groups, three groups of 32 animals each were treated with
      Metformin in their drinking water at a high dose of 200 mg/kg body weight and at
      a low dose of 20 mg/kg body weight; the third group of mice acted as controls.
      Diabetes incidence at 30 weeks of age was similar in all groups. No significant
      differences in the calculated index of insulitis were observed in treated or
      control animals. We conclude that Metformin does not affect the disease process
      leading to clinical diabetes in this animal model.

PMID- 9230347
TI  - Transcription factors contributing to the pancreatic beta-cell phenotype.
AB  - Insulin promoter factor-1 (IPF1) (renamed to pancreatic-duodenal homeobox factor
      1, PDX1) was originally cloned and characterized as an islet beta-cell specific
      insulin gene transcription factor (1) and later shown to be essential for the
      formation of the mature pancreas (2, 3). In the adult normal pancreas PDX1 is
      almost exclusively expressed in the beta-cell compartment and generally absent
      from the alpha-cell while it is widely expressed in the pancreatic epithelium
      during development. Using pluripotent rat islet tumor cultures and derived
      insulinomas and glucagonomas we have analyzed differential expression of a large
      number of genes including the transcription factors PDX1, Nkx6.1, Pax6, and
      NeuroD. While NeuroD and Pax6 expression was detectable among all phenotypes,
      PDX1 was expressed in the pluripotent culture and maintained in the insulinoma,
      while Nkx6.1 was selectively co-induced with insulin during insulinoma formation.
      Both factors were not detectable in the glucagonoma. Nkx6.1 proved to have a
      highly beta-cell restricted expression in the adult rat. Forced expression of
      recombinant PDX1 in the glucagonoma resulted in efficient transcriptional
      activation of the endogenous insulin and IAPP genes, but did not affect glucagon
      gene activity. In this hybrid alpha/beta-cell phenotype the endogenous Nkx6.1
      gene remained silent. We conclude that PDX1 in synergy with NeuroD specifies part
      of the beta-cell phenotype including transcriptional activation of insulin and
      IAPP genes, but that other factors such as Nkx6.1 and Pax6 are required for
      additional features of the fully mature beta-cell phenotype.

PMID- 9230348
TI  - In vitro-generation of islets in long-term cultures of pluripotent stem cells
      from adult mouse pancreas.
AB  - Pancreatic islets of Langerhans exhibit an architecture and cellular organization
      ideal for rapid, yet finely controlled, responses to changes in blood glucose
      levels. In type I, insulin-dependent diabetes (IDD), this organization is lost as
      a result of the progressive autoimmune response which selectively destroys the
      insulin-producing pancreatic beta cells. Since beta cells are perceived as end
      stage differentiated cells having limited capacity for regeneration in situ,
      individuals with IDD resulting from beta cell loss or dysfunction require life
      long insulin therapy. Efforts to produce islet neogenesis or initiate islet
      growth in vitro from either fetal or adult tissue have had minimal success. We
      now report that pancreatic-derived, pluripotent islet-producing stem cells
      (IPSCs), isolated from prediabetic mice, can be grown in long-term cultures and
      differentiated into immature functional islet-like structures containing cells
      which express low levels of insulin, glucagon and/or somatostatin. When such in
      vitro grown islets were implanted into clinically diabetic NOD mice, the
      implanted mice were successfully weaned from insulin long-term (>50 days) without
      ill effects. The implanted mice maintained blood glucose levels just above
      euglycemic (180-220 mg/dl) and showed no signs of disease. Thus, this technical
      breakthrough provides new therapeutic approaches to diabetes as an alternative to
      insulin therapy.

PMID- 9230349
TI  - Induction of pancreatic islet neogenesis.

PMID- 9230350
TI  - Neurotrophin and neurotrophin receptors in islet cells.
AB  - A large number of proteins are found specifically in insulin-producing cells and
      in neuronal cells. The function of neurotrophins in beta cells and the molecular
      mechanism leading to their expression include the expression of functional
      receptors for different neurotrophins. Studies of islet neogenesis also suggest
      that neurotrophins may be important to beta cell maturation. Finally, neuronal
      markers are often detected in beta cells perhaps due to the absence of negative
      regulators of neuron-specific genes.

PMID- 9230351
TI  - Peptide hormone regulation of islet cells.

PMID- 9230352
TI  - Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced
      insulin secretion and the role of lactogenic hormones.
AB  - Pregnancy is a unique event in the life span of islet beta-cells. Under the
      influence of pregnancy islet beta-cells undergo major long term up-regulatory
      structural and functional changes in response to the increased demand for
      insulin. Adaptive changes that occur in islets during normal pregnancy include:
      1) increased glucose-stimulated insulin secretion with a lowered threshold for
      glucose-stimulated insulin secretion, 2) increased insulin synthesis, 3)
      increased beta-cell proliferation and islet volume, 4) increased gap-junctional
      coupling among beta-cells, 5) increased glucose metabolism, and 6) increased c
      AMP metabolism. Of the islet changes that occur during pregnancy the increase in
      beta-cell division and enhanced glucose sensitivity of insulin secretion are most
      notable. The increase in beta-cell division leads to an increase in islet mass
      that contributes to the ability of islets to respond to the increased need for
      insulin. However, the increased glucose sensitivity of beta-cells is likely to be
      more important. The lowering of the threshold for glucose stimulated insulin
      secretion is the primary mechanism by which beta-cells can release significantly
      more insulin under normal blood glucose concentrations. Although the hormonal
      changes which occur during pregnancy are complex, it appears that lactogenic
      influences (either placental lactogen and/or prolactin) are sufficient to induce
      all of the up-regulatory changes that occur in islets during pregnancy. We have
      demonstrated that rat placental lactogens I and II are the hormones responsible
      for up-regulating islets during rodent pregnancy. Although most studies have been
      done using rodent islets, available evidence strongly suggests that human
      placental lactogen and/or human prolactin are the responsible lactogens for up
      regulating islets during human pregnancy. A model for how lactogens up-regulate
      islets during pregnancy is proposed.

PMID- 9230353
TI  - Islet regeneration in IFNgamma transgenic mice.
AB  - The adult pancreas is a developmentally stable organ with limited mitotic
      activity. This minimal mitotic activity proves critical in insulin-dependent
      diabetes mellitus (IDDM) since the pathogenesis is characterized by a selective
      and permanent destruction of islet beta cells. The IFNgamma transgenic mouse
      model of islet regeneration elucidates the differentiation pathway involved in
      the regeneration of functional beta cells from ductal precursors and reveals the
      functional plasticity of the adult pancreas.

PMID- 9230354
TI  - Transgenic overproduction of islet amyloid polypeptide (amylin) is not sufficient
      for islet amyloid formation.
AB  - Islet amyloid polypeptide forms islet amyloid deposits in non-insulin-dependent
      diabetes mellitus. We have generated transgenic mice which express human islet
      amyloid polypeptide in their pancreatic beta cells yet do not develop islet
      amyloid deposits despite producing levels of the amyloidogenic human peptide 2 -
      3 fold higher than the native (mouse) peptide. To determine whether marked
      overproduction of islet amyloid polypeptide is a potential cause of islet amyloid
      formation, we increased expression of this transgene by producing homozygous
      transgenic animals and by making heterozygous mice experimentally insulin
      resistant with nicotinic acid. Pancreatic content of islet amyloid polypeptide
      like immunoreactivity in homozygous and nicotinic acid-treated mice was 2-fold
      (25 +/- 7 fmol/microg; n = 6) and 3.5-fold (47 +/- 20 fmol/microg; n = 3) higher,
      respectively, than that of untreated heterozygous animals (13+/-2 fmol/microg; n
      = 11; both p < 0.05). Despite this marked increase in production of islet amyloid
      polypeptide, neither group of mice developed gross islet amyloid deposits even
      after 16 months of age. We conclude that overproduction of islet amyloid
      polypeptide, even as produced by extreme insulin resistance, is not in itself
      sufficient for islet amyloid formation.

PMID- 9230355
TI  - Does regulatory protein play a role in glucokinase localization?
AB  - The enzyme glucokinase has recently been found to be largely responsible for
      glucose homeostatic responses of both the liver and pancreas. The mechanism(s) of
      these responses remains unknown but recent studies suggest that the intracellular
      localization of glucokinase, controlled by glucokinase regulatory protein, may be
      important. This protein is known to bind to and inhibit glucokinase in a
      phosphofructose-sensitive manner, and we present evidence for the interaction of
      these proteins with F-actin. Glucokinase regulatory protein gelled F-actin, and
      gelation was specifically inhibited by glucokinase and the regulatory protein
      effectors fructose-1-phosphate (F1P) and fructose-6-phosphate (F6P). These
      results suggest that glucokinase regulatory protein may play a role in metabolism
      sensitive glucokinase localization in vivo.

PMID- 9230356
TI  - Commentary on the objectives and efficacy of proficiency testing in microbiology.

PMID- 9230357
TI  - Molecular diagnosis of cat scratch disease: a two-step approach.
AB  - Amplification of Bartonella henselae DNA has been proposed as a diagnostic test
      for cat scratch disease (CSD). The sensitivities of the following three PCR
      assays were compared. PCR/rRNA with universal primers amplifies part of the 16S
      rRNA gene, followed by hybridization with a specific B. henselae probe; PCR/CS
      and PCR/HSP amplify portions of the gltA and the htrA genes, respectively, each
      followed by restriction fragment length polymorphism analysis. The threshold of
      detection of B. henselae DNA in pus was 10(-4), 10(-3), and 10(-2) ng for
      PCR/rRNA, PCR/CS, and PCR/HSP, respectively. By these three assays, B. henselae
      DNA was detected in 100, 94, and 69% of 32 pus and lymph node specimens from CSD
      patients, respectively. The similar sensitivities of the PCR/rRNA and the PCR/CS
      assays for detecting B. henselae DNA in clinical specimens are in contrast to the
      10-fold difference in sensitivities in favor of PCR/rRNA demonstrated with
      purified B. henselae DNA in sterile pus, suggesting that in the majority of
      cases, the bacterial load in clinical specimens is large enough to be identified
      by the PCR/CS assay. A two-step approach is suggested to achieve maximal
      sensitivity for detecting B. henselae in clinical specimens: initial testing by
      PCR/CS (which does not require hybridization), followed by PCR/rRNA with PCR/CS
      negative specimens when CSD is strongly suspected.

PMID- 9230358
TI  - Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella
      henselae-based indirect fluorescence assay and enzyme-linked immunoassay.
AB  - The diagnostic value of the detection of immunoglobulin G (IgG) and IgM by
      Bartonella henselae-based indirect fluorescence assay (IFA) and enzyme-linked
      immunoassay (EIA) for the diagnosis of cat scratch disease (CSD) was evaluated.
      The IFA was performed either with B. henselae that was cocultivated for a few
      hours with Vero cells or with noncocultivated B. henselae as the antigen.
      Additionally, the performance of a Bartonella PCR hybridization assay based on
      the 16S rRNA gene was determined and compared with those of the serologic assays.
      The study group consisted of 45 patients suspected of suffering from CSD by
      fulfilling one or more of the classical criteria. The specificities of the
      immunoassays were set at > or = 95% by analysis of sera from 60 healthy blood
      donors. It is shown that the sensitivities of the IgG assays are very low (40.9%
      for the IFA with noncocultivated B. henselae as antigen) and that those of the
      IgM assays are higher (71.4% for the EIA) for patients who fulfilled two or more
      criteria for CSD. The IgM EIA showed the highest sensitivity: 71.4% in patients
      with two or more criteria for CSD and 80.6% for patients with a positive
      Bartonella PCR result. The results indicate that the specificities of both IFA
      and EIA IgG serologies and the sensitivity of the IFA IgM serology need to be
      improved. The PCR hybridization assay showed a sensitivity of 86.4% for patients
      who fulfilled two or more criteria for CSD and 100% for seven patients who
      fulfilled three or more criteria. The kinetics of IgG and IgM antibody production
      were studied in 18 patients with CSD on the basis of a positive B. henselae IFA
      IgM serology. The results indicate that there is no standard course of anti-B.
      henselae IgG and IgM production in patients with CSD, because some patients
      produced high levels of both IgG and IgM, others produced only high levels of
      IgM, and a few patients produced only low levels of antibodies.

PMID- 9230359
TI  - Evaluation of a commercial enzyme-linked immunosorbent assay for detection of
      immunoglobulin M antibody in diagnosis of human leptospiral infection.
AB  - The PanBio Leptospira immunoglobulin M (IgM) enzyme-linked immunosorbent assay
      (ELISA) is a commercially available screening test for the diagnosis of acute
      leptospiral infection. The ability of the test to diagnose early or recent
      Leptospira interrogans infection was assessed by testing sera with known
      microagglutination test (MAT) titers to serovars pomona, hardjo, copenhageni, and
      australis. The IgM ELISA detected all 41 cases of early or recent leptospiral
      infection (sensitivity, 100%), with a positive ELISA result seen in many cases
      before MAT antibody titers reached 1:50. Thirty-eight of 41 patients showed
      seroconversion (fourfold or greater increase in titer by MAT, 2 of 41 patients
      had a single sample with elevated titer, and 1 patient from whom leptospires were
      isolated from a blood sample failed to show MAT titers, despite a seroconversion
      (negative to positive result) in the ELISA. Follow-up sera obtained from 8 of 12
      patients (67%) for 3 to 48 months after the acute stage of illness showed
      persisting IgM antibody. However, the range of levels detected in these samples
      (maximum ELISA ratio, 2.0) was lower than the range seen when infection was
      recent. Reactivity in the IgM ELISA was observed for only 1 of 59 serum samples
      from asymptomatic donors (specificity, 98%) and 16 of 233 serum samples from
      patients with Ross River virus, brucella, Epstein-Barr virus, cytomegalovirus,
      mycoplasma, Q-fever, toxoplasma, hepatitis A virus, Treponema pallidum, or
      Borrelia burgdorferi infection (specificity, 93%), with the majority of these
      patients showing lower levels of IgM in comparison to those in patients with
      leptospiral infection. We conclude that this ELISA is sufficiently sensitive for
      use as an initial screen for leptospiral infections, with subsequent confirmation
      of positive test results by MAT.

PMID- 9230360
TI  - A case of tick-borne encephalitis in Japan and isolation of the the virus.
AB  - A case of tick-borne encephalitis (TBE) has not been reported for many years in
      Japan, although a serological survey of sera from domestic animals suggested the
      presence of TBE foci in Hokkaido, the northern island of Japan. Studies were
      conducted to prove the presence of an endemic focus of TBE virus in Japan by
      means of serology and virus isolation. In October 1993 in Hokkaido, a severe case
      of encephalitis in a dairy farmer's wife was diagnosed as TBE. Serological
      examination of paired serum specimens showed a rise in the neutralization
      antibody titer to Russian spring summer encephalitis virus. A
      seroepizootiological survey of dogs showed that the TBE-related virus was
      prevalent in the area. Three virus isolates were obtained from the blood of
      sentinel dogs, and antigenic analysis grouped the isolates into TBE-related
      viruses. Sequence analysis of the envelope protein gene identified one of the
      isolates as being of the same subtype as the Russian spring summer encephalitis
      (Far Eastern TBE) virus. The results provide evidence that TBE is endemic in a
      certain area of Japan.

PMID- 9230361
TI  - Evaluation of transport media for Pasteurella multocida isolates from rabbit
      nasal specimens.
AB  - A suitable medium for the transport of Pasteurella multocida in nasal specimens
      from rabbits was investigated by using pure cultures of the organism and nasal
      swabs from infected rabbits. First, the ability of eight transport media to
      preserve the viabilities of P. multocida strains isolated from rabbits was
      studied. Cary-Blair medium and Leibovitz medium no. 15 (L-15) were found to be
      superior to the other six media tested, enabling survival of the organism for
      more than 14 days at room temperature. Second, the survival of P. multocida in
      nasal specimens was evaluated on both Cary-Blair medium and L-15. The recovery
      rate of the organism from these two media was more than 80 to 90% during 4 days
      of storage and decreased gradually with increasing preservation time. There were
      no significant differences (P > 0.05) in recovery rates of the organism between
      Cary-Blair medium and L-15. On the basis of these results, we recommend the use
      of Cary-Blair medium for the transport of P. multocida in rabbit nasal specimens
      because of the ease of transport of nasal swabs by mail.

PMID- 9230362
TI  - HEp-2 cell adherence patterns, serotyping, and DNA analysis of Escherichia coli
      isolates from eight patients with AIDS and chronic diarrhea.
AB  - Three morphologic patterns of interaction between bacteria and enterocytes have
      been observed in colonic biopsy specimens from AIDS patients with chronic
      diarrhea in the United States. The DNA encoding virulence factors and the HEp-2
      cell adherence patterns of Escherichia coli strains isolated from the stools of
      eight symptomatic AIDS patients were compared with those of five control strains
      with known adherence patterns. One clinical isolate from a patient with attaching
      and-effacing enteropathy displayed the localized adherence attaching-and-effacing
      pattern typical of enteropathogenic E. coli on HEp-2 cells, five isolates
      displayed the "stacked-brick" aggregative adherence pattern typical of
      enteroaggregative E. coli strains, and one isolate showed the pattern
      characteristic of diffusely adherent E. coli. One patient's isolate displayed
      features of all three patterns. No clinical isolate hybridized with standard
      probes for enteropathogenic, enteroaggregative, diffusely adherent,
      enterotoxigenic, and enteroinvasive E. coli strains. Thus, isolates from
      symptomatic AIDS patients in the United States can display the same interactive
      patterns with HEp-2 cells as the agents of pediatric or traveler's diarrhea, but
      lack their typical virulence factors.

PMID- 9230363
TI  - Heterogeneity and clonality among isolates of Mycobacterium kansasii:
      implications for epidemiological and pathogenicity studies.
AB  - The reservoir and transmission route of Mycobacterium kansasii are largely
      unknown. In addition, culturing of M. kansasii from human sources is not proof of
      disease because it may represent colonization rather than infection.
      Unfortunately, investigation of the epidemiology and pathogenicity of M. kansasii
      is complicated by evidence of heterogeneity within the species. A comprehensive
      study by detailed genotypic analysis of a large collection of M. kansasii
      isolates (n = 276) from various geographical sources within Europe was conducted.
      Five defined subtypes of M. kansasii were identified; of these subtypes, type I
      represents the most common isolate from humans. Although phylogenetic analysis
      confirmed its relationship to the other M. kansasii types, significant sequence
      divergence was found at the 16S-23S intergenic spacer. Analysis of the
      chromosomal polymorphism of type I demonstrated a marked clonal structure for
      this particular organism. Because M. kansasii is becoming a significant pathogen
      among immunodeficient hosts, future epidemiological and pathogenicity studies
      should take into consideration both the heterogeneity within the species and the
      apparent clonality of the most prevalent M. kansasii isolates infecting humans.

PMID- 9230364
TI  - Analysis of the thermostable direct hemolysin (tdh) gene and the tdh-related
      hemolysin (trh) genes in urease-positive strains of Vibrio parahaemolyticus
      isolated on the West Coast of the United States.
AB  - Urease-positive (Ure+) and urease-negative (Ure-) strains of Vibrio
      parahaemolyticus isolated from patients on the West Coast of the United States
      between 1979 and 1995 were analyzed for the thermostable direct hemolysin (tdh)
      gene and the tdh-related hemolysin (trh) genes (trh1 and trh2). The DNA colony
      hybridization method with the polynucleotide probes was used to determine the
      distribution of the genes. Of 60 Ure+ strains, 59 strains (98%) had the trh
      (either trh1 or trh2) gene and 54 strains (90%) carried the tdh gene. The absence
      of the trh gene or a related sequence in an exceptional Ure+ strain was confirmed
      by Southern blot analyses. The stronger correlation with the trh gene than with
      the tdh gene was mostly attributable to strains possessing only the trh2 gene. Of
      25 Ure- strains, 20 strains (80%) had the tdh gene but none had the trh gene.
      These results indicate a very strong correlation between the Ure+ phenotype and
      the trh gene and are consistent with those reported for strains isolated in Asia.
      The Ure+ strains carrying the trh genes were not restricted to a unique group of
      the strains. The O4:K12 strains carrying the trh1 gene have predominantly been
      isolated since 1979. However, strains of various non-O4:K12 serovars carrying
      either the trh1 or the trh2 gene became predominant after 1992. In addition,
      analysis by the arbitrarily primed PCR method revealed two subgroups within the
      selected Ure+ O4:K12 strains. Hybridization tests with oligonucleotide probes
      demonstrated that the trh1 sequences of the West Coast strains differ to some
      extent from those of Asian strains. Nevertheless, a PCR method previously
      established to detect both the trh1 and the trh2 genes in Asian strains could
      detect 98% of those genes in the West Coast strains.

PMID- 9230365
TI  - Improved diagnosis of primary Toxoplasma gondii infection in early pregnancy by
      determination of antitoxoplasma immunoglobulin G avidity.
AB  - The ability to discriminate between primary Toxoplasma gondii infection acquired
      in early pregnancy and infection that occurred prior to pregnancy was assessed by
      an enzyme immunoassay (EIA) to determine the avidity of toxoplasma-specific
      immunoglobulin G (IgG). The results were compared to those of the Platelia Toxo
      IgM EIA and the dye test. The mean IgG avidity of 73 serum samples collected
      within 20 weeks after the estimated time of infection was 5.9%. Among 26 serum
      samples showing latent infection (toxoplasma-specific IgG positive and IgM
      negative) and 56 IgM-positive serum samples with a low dye test titer (<300
      IU/ml), the mean avidities were 51.3 and 57.5%, respectively. A total of 72.8% of
      92 IgM-positive serum samples with a high dye test titer (>300 IU/ml), suggesting
      a recent toxoplasma infection, had an IgG avidity of >20%, indicating that the
      infection started more than 20 weeks earlier. By introducing high IgG avidity as
      a criterion in the first half of pregnancy to exclude the possibility that
      toxoplasma infection was acquired during gestation, many women will avoid
      unnecessary examinations, treatment, and anxiety.

PMID- 9230366
TI  - Corynebacterium imitans sp. nov. isolated from patients with suspected
      diphtheria.
AB  - A 5-month-old boy of a Romanian family traveling via Ukraine to Poland developed
      a respiratory disease that resembled and that was initially diagnosed as
      pharyngeal diphtheria. The child recovered after treatment with antidiphtheria
      antitoxin. A coryneform bacterium had been isolated from a nasopharyngeal
      specimen from the child and was initially identified as an atypical
      Corynebacterium diphtheriae strain. Seven adults who had contact with either the
      child or an adult contact person also developed symptoms of pharyngeal
      diphtheria, were also treated with antitoxin, and recovered uneventfully.
      Coryneform bacteria similar to that originating from the index patient were also
      isolated from the throat swabs of three adults. Detailed biochemical and
      chemotaxonomic investigations revealed that the coryneform bacteria belonged to
      the genus Corynebacterium and could be differentiated from all other defined
      species of this genus. Ribotyping and pulsed-field gel electrophoresis
      demonstrated that all four patients' isolates were of clonal origin. The
      diphtheria toxin gene and its product were not detected either by PCR assays or
      by the Elek test, making a possible disease association of the Corynebacterium
      more unlikely. Comparative 16S rRNA gene sequence analysis revealed that the
      coryneform bacterium represented a new subline within the genus Corynebacterium,
      for which the name Corynebacterium imitans sp. nov. is proposed. The type strain
      is NCTC 13015 (DSM 44264; CCUG 36877).

PMID- 9230367
TI  - Exfoliative toxin detection using reversed passive latex agglutination: clinical
      and epidemiologic applications.
AB  - A rapid and simple method for detecting exfoliative toxin serotypes A and B from
      clinical isolates has been developed as a test kit (EXT-RPLA; Denka Seiken Co.
      Ltd., Niigata, Japan). This method is based on reversed passive latex
      agglutination. The detection limit of the EXT-RPLA observed for purified
      exfoliative toxin serotypes A and B was 1 ng/ml. We evaluated the clinical and
      epidemiologic uses of the EXT-RPLA. A total of 381 isolates of Staphylococcus
      aureus, 292 from various clinical specimens and 89 from the skin of dermatologic
      patients, were studied. The EXT-RPLA detected 19 exfoliative toxin producers,
      including 16 serotype A producers and 3 serotype B producers, but no double
      producers. The sensitivity and specificity of the EXT-RPLA were confirmed by the
      newborn mouse bioassay and a PCR assay for the structural genes for exfoliative
      toxin serotypes A and B (eta and etb, respectively). The overall positivity rate
      of exfoliative toxin producers was 5.0% (19 of 381), including 16 serotype A
      isolates and 3 serotype B isolates. Of the 89 isolates from the skin of
      dermatologic patients, 12 (13.5%) were positive for exfoliative toxin production.
      Only 2 (1.3%) of the 153 methicillin-resistant S. aureus isolates produced
      exfoliative toxin, while 17 (7.5%) of the 228 methicillin-sensitive isolates
      produced exfoliative toxin. The EXT-RPLA assay is a simple and reliable method
      for detecting exfoliative toxin, and we recommend its use for the rapid diagnosis
      of staphylococcal scalded skin syndrome. We also recommend its use for detection
      of this syndrome so that effective control measures can be taken against the
      spread of this syndrome.

PMID- 9230368
TI  - Phylogenetic placement and characterization of a new alpha-2 proteobacterium
      isolated from a patient with sepsis.
AB  - An alpha-2 proteobacterium, previously unknown as determined by its phylogenetic
      characteristics and the DNA sequence of its 16S rRNA gene, was isolated from a
      patient who presented an unusual clinical picture, including high remitting fever
      and multiorgan involvement. The bacterium was detected in multiple plasma
      samples, obtained during the acute phase of the disease, after cocultivation in
      cell culture media. Electron microscopy of the organism showed a three-layer
      laminar cell wall and electron-dense granules within the cytoplasm, as well as a
      polar flagellum. By means of PCR followed by sequencing of amplified 16S
      ribosomal DNA fragments, the bacterium was found to differ from all species for
      which ribosomal sequence information is available. It is here provisionally named
      the Rasbo bacterium. At a subsequent relapse, the bacterium was identified in
      pericardial fluid both by PCR/sequencing and by direct electron microscopy. At a
      second relapse, it was again cultured from plasma. After in vitro adaptation to
      solid media, the MICs of various antibiotics could be determined. A transient
      immunoglobulin M (IgM) but no IgG response to the bacterium was found by an
      indirect immunofluorescence test, as well as by an immobilization test during the
      acute phase of the disease.

PMID- 9230369
TI  - Evaluation of the semiautomated Abbott LCx Mycobacterium tuberculosis assay for
      direct detection of Mycobacterium tuberculosis in respiratory specimens.
AB  - Five hundred twenty processed respiratory specimens from 326 patients received
      for the diagnosis of tuberculosis or other mycobacterial infections were tested
      by means of the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories,
      which uses ligase chain reaction technology for the direct detection of M.
      tuberculosis complex in respiratory specimens. The results of the LCx M.
      tuberculosis Assay were compared with the results of culture and staining
      techniques. After a combination of culture results and the patient's clinical
      data, a total of 195 specimens were collected from 110 patients who were
      positively diagnosed as having pulmonary tuberculosis. Twenty-three of these 195
      specimens which corresponded to 10 patients with a history of pulmonary
      tuberculosis (TB) and anti-TB treatment ranging from 1 to 6 months were culture
      negative. The other 172 specimens were culture positive for M. tuberculosis. With
      an overall positivity rate of 37.5% (195 of 520 specimens), the sensitivity,
      specificity, and positive and negative predictive values were 90.8, 100, 100, and
      94.7%, respectively, for the LCx M. tuberculosis Assay; 88.2, 100, 100, and
      93.4%, respectively, for culture; and 82.6, 92, 72.9, and 97.6%, respectively,
      for acid-fast staining. For 161 specimens (82.6%) from patients smear positive
      for the disease and 34 specimens (17.4%) from patients smear negative for the
      disease, the sensitivity values for the LCx M. tuberculosis Assay were 98.8 and
      53%, respectively. There were no statistically significant differences in the
      sensitivities and specificities between the LCx M. tuberculosis Assay and culture
      (P > 0.05). Conclusively, the LCx M. tuberculosis Assay has proved to have an
      acceptable sensitivity and a high specificity in detecting M. tuberculosis and
      has the potential of reducing the diagnosis time to an 8-h working day.

PMID- 9230370
TI  - Microbiologic and clinical value of primary broth cultures of wound specimens
      collected with swabs.
AB  - In order to assess the microbiologic and clinical value of primary broth culture
      of wound specimens collected with swabs and submitted to the laboratory in
      transport medium, we compared the results of primary agar culture with the
      results of a corresponding primary broth culture for 344 aerobic specimens and
      176 anaerobic specimens. While 8.7% (45 of 520) of the specimens yielded
      organisms from the primary broth culture that were not recovered from the
      corresponding primary agar culture, only 5.0% (26 of 520) of the specimens
      yielded organisms from the primary broth culture other than Staphylococcus
      epidermidis, viridans group streptococci, and Corynebacterium spp. Moreover, the
      primary broth culture of only 0.6% (3 of 520) of the specimens yielded organisms
      not recovered from the primary agar culture that caused a change in the therapy
      of the patient. Our conclusion is that primary broth cultures are unnecessary for
      the processing of wound specimens properly collected with swabs.

PMID- 9230371
TI  - Controlled comparison of bioMerieux VITAL and BACTEC NR-660 systems for detection
      of bacteremia and fungemia in pediatric patients.
AB  - The bioMerieux VITAL automated blood culture system measures a decrease in
      fluorescence to detect the presence of microorganisms in blood. To assess the
      performance of VITAL with AER aerobic medium versus that of the nonradiometric
      BACTEC NR-660 PEDS PLUS medium for the detection of sepsis in children, a total
      of 12,146 blood specimens were collected at three university medical centers and
      inoculated into AER and PEDS PLUS bottles that were weighed before and after
      filling. The sample volumes were considered adequate in 6,276 bottle pairs. The
      total yield of isolates was 629, of which 489 (78%) were judged to be the cause
      of true infections. Staphylococci (P < 0.001) and yeasts (P < 0.05) were detected
      more often in PEDS PLUS bottles, as were all microorganisms combined (P < 0.001).
      The improved detection in the PEDS PLUS medium was most marked for patients on
      antimicrobial therapy (P < 0.001), but remained statistically significant even
      for patients not on therapy (P < 0.025). There were 431 episodes of sepsis,
      including 407 considered adequate for analysis. Of the 363 unimicrobial episodes,
      278 were detected by both bottles, 64 were detected by PEDS PLUS bottles only,
      and 21 were detected by AER bottles only (P < 0.01). No false-negative cultures
      were detected by terminal subculture of the PEDS PLUS bottles when the companion
      AER bottle was positive. However, there were 14 false-negative cultures (7
      yeasts, 5 staphylococci, 1 Enterococcus faecalis, and 1 Enterobacter sp.) on
      terminal subculture of the AER bottles when the companion PEDS PLUS bottle was
      positive. When both systems were positive, the VITAL system detected bacteria
      earlier than did the BACTEC system by a mean of 1.6 h. Also, false-positive
      signals were less common with the VITAL system. We conclude that the VITAL system
      with AER medium must be modified to improve the detection of clinically important
      staphylococci and yeasts if it is to perform comparably to the BACTEC NR-660
      nonradiometric system with PEDS PLUS medium for a pediatric population.

PMID- 9230372
TI  - Flow cytometric detection of Cryptosporidium oocysts in human stool samples.
AB  - Cryptosporidium parvum is an important pathogen that causes diarrhea in virtually
      all human populations. Improved diagnostic methods are needed to understand the
      risk factors, modes of transmission, and impact of cryptosporidiosis. In the
      present study, we fluorescently labeled and counted C. parvum oocysts by flow
      cytometry (FC) and developed a simple and efficient method of processing human
      stool samples for FC analysis. Formed stool (suspended in phosphate-buffered
      saline) from an asymptomatic, healthy individual was seeded with known
      concentrations of oocysts, and oocysts were labeled with a cell wall-specific
      monoclonal antibody and detected by FC. The method described herein resulted in a
      mean oocyst recovery rate of 45% +/- 16% (median, 42%), which consistently
      yielded a fourfold increase in sensitivity compared to direct fluorescent
      antibody assay of seeded stool samples. However, in many instances, FC detected
      as few as 10(3) oocysts per ml. Thus, FC provides a reproducible and sensitive
      method for C. parvum oocyst detection.

PMID- 9230373
TI  - Ehrlichia phagocytophila genogroup rickettsiae in ixodid ticks from California
      collected in 1995 and 1996.
AB  - A total of 1,246 ixodid ticks collected in 1995 and 1996 from seven California
      counties were examined for the presence of Ehrlichia phagocytophila genogroup
      rickettsiae by using a nested PCR technique. Of 1,112 adult Ixodes pacificus
      Cooley and Kohls ticks tested, nine pools, each containing five ticks, were
      positive (minimum percentage of ticks harboring detectable ehrlichiae, 0.8%).
      Positive ticks were limited to four of the seven counties (Sonoma, El Dorado,
      Santa Cruz, and Orange). In Santa Cruz County, three positive pools were
      identified at the home of an individual with prior confirmed human granulocytic
      ehrlichiosis. In El Dorado County, positive ticks were found at sites where cases
      of granulocytic ehrlichiosis in a horse and a llama had recently occurred. Among
      47 nymphal I. pacificus ticks collected in Sonoma County, one positive pool was
      identified. Fifty-seven adult Dermacentor occidentalis Marx and 30 adult D.
      variabilis Say ticks, collected chiefly in southern California, were negative.
      These data, although preliminary, suggest that the prevalence of E.
      phagocytophila genogroup rickettsiae in ixodid ticks of California may be lower
      than in cognate vector populations (i.e., I. scapularis Say = I. dammini
      Spielman, Clifford, Piesman, and Corwin) in the eastern and midwestern United
      States.

PMID- 9230375
TI  - Rapid characterization schemes for surveillance isolates of vancomycin-resistant
      enterococci.
AB  - Surveillance cultures for vancomycin-resistant enterococci (VRE) and subsequent
      characterization of the isolates can be extremely burdensome and difficult.
      Therefore, efficient and reliable schemes for the characterization of
      surveillance isolates are needed. In this study, a commercial agar (bile esculin
      azide agar with 6 microg of vancomycin per ml [BEAA]; Remel, Lenexa, Kans.) was
      used in the initial screening step to establish relatively rapid (i.e., in < or =
      24 h from the time of isolation) phenotype-based and PCR-based schemes for the
      detection and characterization of VRE. The phenotype-based scheme included Gram
      staining of growth on BEAA and subculture of cocci on sheep blood agar plates for
      vancomycin disk diffusion and pyrazinamidase (PYR) testing. For the PCR scheme,
      inocula for van gene detection were taken directly from the BEAA plates. The
      phenotypic approach was applied to 378 surveillance cultures that yielded growth
      on BEAA. Gram staining quickly eliminated gram-positive bacilli from further
      testing, and a negative PYR test classified 25 additional isolates as probable
      pediococci. A positive PYR test reliably identified 121 single-patient VRE
      isolates that included 83 Enterococcus faecium, 33 E. gallinarum, and 5 E.
      casseliflavus strains. The vancomycin inhibition zone size clearly distinguished
      VanA and VanB strains from VanC strains within 24 h of BEAA isolation. All VanA
      and VanB strains failed to produce zones of >6 mm, while only one VanC strain
      produced a zone of < 15 mm. Challenging this phenotypic scheme with 47 stock VRE
      isolates produced similar findings. In direct PCR analyses, false-negative vanA
      and vanB results occurred with 12% of the specimens. Many of the false-negative
      reactions also failed to produce an internal control product, which underscores
      the need for including control primers when a PCR scheme is used. In summary, the
      phenotype- and the PCR-based schemes provide efficient methods for characterizing
      VRE within 24 h of isolation.

PMID- 9230374
TI  - Mycobacterium growth indicator tube testing in conjunction with the AccuProbe or
      the AMPLICOR-PCR assay for detecting and identifying mycobacteria from sputum
      samples.
AB  - We have compared the ability of the Mycobacterium Growth Indicator Tube (MGIT)
      system, a new culture method with an oxygen-sensitive fluorescent sensor, to
      recover mycobacteria from sputum samples with the abilities of egg-based medium
      and the Septi-Chek AFB system. We have also assessed the clinical utility of the
      AccuProbe or the AMPLICOR-PCR assay to directly identify Mycobacterium
      tuberculosis complex and M. avium-M. intracellulare complex (MAC) from positive
      MGITs. From 382 sputum samples, 99 isolates of M. tuberculosis complex and 20
      isolates of MAC were recovered. The MGIT system had the highest recovery rates
      for M. tuberculosis complex (97.0%) and MAC (100%), compared to recovery rates of
      51.5 and 65.0%, respectively, with the egg-based medium and 81.8 and 85.0%,
      respectively, with the Septi-Chek AFB system. The shortest recovery times were
      also achieved with the MGIT system: 16.6 days for M. tuberculosis complex and
      12.0 days for MAC, compared to 27.1 and 20.1 days, respectively, with the egg
      based medium and 21.4 and 13.2 days, respectively, with the Septi-Chek AFB
      system. The AccuProbe identified 74 (77.1%) of the 96 M. tuberculosis complex
      positive MGITs and 17 (85.0%) of the 20 MAC-positive vials. The AMPLICOR system
      correctly identified 94 (97.9%) of the 96 M. tuberculosis complex-positive MGITs
      and all 20 MAC-positive vials. Therefore, the MGIT system used in conjunction
      with the AMPLICOR system is a rapid and sensitive method for detecting and
      identifying M. tuberculosis complex and MAC isolates from sputum samples.

PMID- 9230376
TI  - Identification of Candida species by randomly amplified polymorphic DNA
      fingerprinting of colony lysates.
AB  - We have characterized a method that produces simple yet diagnostic fingerprints
      that are unique to isolates of Candida species. DNA from individual colonies can
      be amplified from crude single-colony lysates. Randomly amplified polymorphic DNA
      (RAPD) fingerprints generated from a single primer correctly identified the
      species of most (>98%) of the isolates identified with CHROMagar Candida plates
      as non-Candida albicans Candida species. RAPD fingerprints were much more
      informative than the plates, since they distinguished between all tested species
      and required less time. Most (91%) of these identifications agreed with those
      assigned by API 20C tests. In almost every incident of species identity mismatch,
      electrophoretic karyotyping showed that the RAPD fingerprint was correct. This
      underscores the improved objectivity and reliability of this method over those of
      conventional diagnostic tools. The identities of approximately 30% of C. albicans
      isolates identified in clinical laboratories by positive germ tube tests are not
      verified by either testing on CHROMagar Candida plates or RAPD fingerprinting.
      Data suggest that clinical isolates conventionally identified as C. albicans in
      clinical settings are heterogeneous, consisting of both misidentified and
      atypical yeasts. RAPD fingerprints obtained from primary culture plate colonies
      allows for rapid, highly accurate determinations of Candida species, hence
      permitting earlier selection of appropriate antifungal agents in the clinical
      setting.

PMID- 9230377
TI  - Pseudo-outbreak of septicemia due to rapidly growing mycobacteria associated with
      extrinsic contamination of culture supplement.
AB  - Between April and December 1994, 23 blood cultures from human immunodeficiency
      virus-infected patients grew rapidly growing mycobacteria suspected to be
      Mycobacterium chelonae at a hospital in New Jersey. The isolates were later
      identified as M. abscessus. Several bacterial species, including M. abscessus,
      were cultured from an opened multidose supplement vial (BBL Septi-Chek AFB
      Supplement) that had been used for mycobacterial blood cultures. The M. abscessus
      isolates from case patients and the supplement vial had identical multilocus
      enzyme electrophoresis and antimicrobial susceptibility patterns. Finding a
      contaminated vial of supplement, together with the lack of a distinct syndrome in
      case patients, was consistent with a pseudo-outbreak.

PMID- 9230378
TI  - Application of a nested, multiplex PCR to psittacosis outbreaks.
AB  - We developed a nested, multiplex PCR for simultaneous detection of three species
      of chlamydiae in human and avian specimens. The PCR was designed to increase
      sensitivity and to circumvent inhibitors of PCR present in clinical specimens.
      The target sequence was the 16S rRNA gene. The first-step PCR was genus specific,
      and the second-step PCR was multiplexed (i.e., had multiple primer sets in the
      same tube) and could discriminate among Chlamydia pneumoniae, Chlamydia psittaci,
      and Chlamydia trachomatis on the basis of the molecular weight of the amplicon.
      The limit of detection of each of the two PCR steps was 5 inclusion-forming
      units. We used PCR and serologic evidence during outbreaks of psittacosis to
      infer that C. psittaci had been transmitted from birds purchased in pet stores to
      humans. We also used this method to test both live and dead birds from pet stores
      for infection with C. psittaci. Compared with culture, the application of PCR to
      avian specimens increased the rate of C. psittaci detection.

PMID- 9230379
TI  - Use of recombinant human antibody fragments for detection of cytomegalovirus
      antigenemia.
AB  - The determination and quantitation of peripheral blood leukocytes (PBLs)
      expressing human cytomegalovirus (HCMV) antigens is widely employed in clinical
      virology for rapid diagnosis of HCMV-related infections. We describe how CMV
      antigenemia may be accurately detected by means of human recombinant monoclonal
      Fab fragments rescued from a combinatorial phage display library prepared from an
      HCMV-infected donor. Fourteen recombinant Fabs were tested against HCMV-positive
      PBLs from a patient with ongoing HCMV infection. Three clones were found to react
      specifically with the nuclei of these cells. These three recombinant Fabs were
      subsequently tested, individually and pooled together, against 60 PBL samples
      taken from immunosuppressed patients. The reactivity observed was comparable to
      that obtained with mouse monoclonal antibodies commercially available for this
      purpose. The three recombinant Fabs were shown to react specifically with the 65
      kDa viral tegument phosphoprotein encoded by UL83 (pUL83), which is the most
      abundant viral antigen in HCMV-infected PBLs.

PMID- 9230380
TI  - Evaluation of the premier EHEC assay for detection of Shiga toxin-producing
      Escherichia coli.
AB  - An enzyme-linked immunosorbent assay for the detection of Shiga toxins (Premier
      EHEC assay; Meridian Diagnostics, Inc.) was compared to conventional sorbitol
      MacConkey culture for the recovery of enterohemorrhagic Escherichia coli. A total
      of 74 enteric pathogens, including 8 E. coli O157:H7 isolates, were recovered
      from 974 stool specimens. Two of these specimens were not tested by Premier
      assaying due to insufficient sample and are not considered in the data analysis.
      The Premier EHEC assay detected the 6 evaluable specimens which were culture
      positive for E. coli O157:H7 and identified an additional 10 specimens as
      containing Shiga toxin. Seven isolates were recovered from these 10 specimens by
      an immunoblot assay and were confirmed as toxin producers by a cytotoxin assay.
      Of these seven, four isolates were serotype O157:H7, one was O26:NM, one was O6:H
      , and one was O untypeable:H untypeable. Three specimens contained Shiga toxin by
      both EHEC immunoassaying and cytotoxin testing; however, no cytotoxin-producing
      E. coli could be recovered. The sorbitol-MacConkey method had a sensitivity and a
      specificity of 60 and 100%, respectively, while the Premier EHEC assay had a
      sensitivity and a specificity of 100 and 99.7%, respectively, for E. coli O157:H7
      only. The Premier EHEC assay also detected an additional 20% Shiga toxin
      producing E. coli (STEC) that were non-O157:H7. Thus, the Premier EHEC assay is a
      sensitive and specific method for the detection of all STEC isolates. Routine use
      would improve the detection of E. coli O157:H7 and allow for determination of the
      true incidence of STEC other than O157:H7. The presence of blood in the stool
      and/or the ages of the patients were poor predictors of the presence of STEC.
      Criteria need to be determined which would allow for the cost-effective
      incorporation of this assay into the routine screen for enteric pathogens in high
      risk individuals, especially children.

PMID- 9230382
TI  - Detection and clinical significance of extended-spectrum beta-lactamases in a
      tertiary-care medical center.
AB  - The prevalence of extended-spectrum beta-lactamase (ESBL)-mediated resistance
      remains unknown for most hospitals, and national guidelines for testing and
      reporting ESBL-mediated resistance have not yet been developed. We undertook a
      study to determine the prevalence of ESBLs and the clinical need for testing in
      our tertiary-care medical center. Members of the family Enterobacteriaceae
      isolated over a 6-month period for which ceftazidime or ceftriaxone MICs were
      greater than 1 microg/ml were tested for production of ESBLs by the double-disk
      synergy method. Approximately 1.5% of isolates of the family Enterobacteriaceae
      (50 of 3,273), which were isolated from 1.2% of patients (23 of 1,844), were
      found to express ESBLs. ESBL-producing strains included eight different species
      and were isolated from patients located throughout the hospital, including
      outpatient clinics. By using the interpretive guidelines of the National
      Committee for Clinical Laboratory Standards, 26 to 39% of the isolates would have
      been reported to be susceptible to ceftazidime, depending upon the routine
      susceptibility method used. However, tests with cefpodoxime found all of the ESBL
      producing strains to be resistant or intermediate. Nine patients infected with
      ESBL-producing isolates were treated with therapy which included an expanded
      spectrum cephalosporin. Seven were cured. The deaths of the other two patients
      were not attributed to bacterial resistance missed by routine susceptibility
      testing. These observations suggest that in our tertiary-care medical center, it
      may not be clinically necessary or cost-effective at this time to institute
      additional testing on a routine basis to detect ESBL production in all clinical
      isolates of the family Enterobacteriaceae.

PMID- 9230383
TI  - Mycobacterial growth and bacterial contamination in the mycobacteria growth
      indicator tube and BACTEC 460 culture systems.
AB  - The BACTEC 460 system currently provides the most rapid detection of
      mycobacterial growth, but the system is radiometric and requires needles to
      inoculate specimens through the bottle's septum. The Mycobacteria Growth
      Indicator Tube (MGIT) system has a liquid medium, like the BACTEC system, and
      does not require needles when inoculating specimens. We compared mycobacterial
      growth from 510 specimens in the two systems. Average time to acid-fast bacillus
      (AFB) detection and identification to the species level was less with the BACTEC
      system, but this result was statistically significant only for AFB detection in
      specimens containing Mycobacterium avium-M. intracellulare complex. The
      contamination rate with MGIT was 29%; the BACTEC rate was 5%. To investigate MGIT
      contamination, we initiated a second study with changes in specimen processing.
      The MGIT contamination rate was reduced to 12%; the BACTEC rate was not
      significantly affected (5.5%). The most likely explanation for the contamination
      in MGIT is the richness of its medium compared to the BACTEC medium. Cost
      analysis for the two systems in a laboratory that processes 4,500 specimens a
      year is presented. The data suggest that the BACTEC 460 and the MGIT systems are
      approximately equivalent in cost and ability to support the growth of AFB. The
      MGIT system appears safer and easier to use and was preferred by laboratory
      personnel, but it cannot currently be used for blood specimens or
      antituberculosis susceptibility testing.

PMID- 9230381
TI  - Genotypic analysis of Burkholderia cepacia isolates from 13 French cystic
      fibrosis centers.
AB  - Burkholderia cepacia has been involved in outbreaks of pulmonary infection among
      patients with cystic fibrosis (CF), and the spread of a highly transmissible
      clone has been reported throughout the United Kingdom and Canada. These data
      prompted a DNA-based typing study of the strains recovered in French CF centers.
      Ninety-five isolates recovered from 71 patients attending 13 CF centers in 9
      regions of France were characterized by randomly amplified polymorphic DNA (RAPD)
      analysis and pulsed-field gel electrophoresis (PFGE). Twenty-one genotypes were
      identified among the 95 isolates, and the results of RAPD and PFGE were
      concordant for 89 isolates (94%). Cross-colonization was demonstrated in 7 of the
      13 CF centers. The investigation of serial isolates showed that most chronically
      colonized patients harbored a single B. cepacia strain. A geographically
      clustered distribution of B. cepacia genotypes was observed, except for one
      genotype, which was detected in four regions but was proven to be different from
      the genotype of the British-Canadian highly transmissible strain. The present
      study confirms the ability of B. cepacia to spread among CF communities in France
      and the importance of epidemiological surveys in the institution of prevention
      policies.

PMID- 9230384
TI  - Evaluation of a nonradiometric system (BACTEC 9000 MB) for detection of
      mycobacteria in human clinical samples.
AB  - This study was carried out to evaluate the rate of recovery and time required for
      detection of mycobacteria from pulmonary and extrapulmonary human clinical
      samples, by using a fluorescence-quenching-based oxygen sensor (BACTEC 9000 MB;
      Becton Dickinson Microbiology Systems, Sparks, Md.). The results were compared
      with those obtained by microscopy, conventional culture in Lowenstein-Jensen (LJ)
      medium, and a BACTEC radiometric system (BACTEC 460 TB; Becton Dickinson). Of the
      779 clinical samples processed, 364 from pulmonary sites and 415 from
      extrapulmonary sites, 62 (7.9%) were positive for mycobacterial isolates; of the
      positive samples, 59 (95.1%) were detected with the fluorescent BACTEC 9000 MB
      system, 57 (91.9%) were detected with the radiometric system (BACTEC 460 TB), and
      43 (69.3%) were detected with LJ conventional culture. The mean times to
      detection of all mycobacteria with BACTEC 9000 MB and BACTEC 460 TB were similar
      (10.3 and 10.0 days, respectively). The results obtained indicate that the
      nonradiometric BACTEC (BACTEC 9000 MB) system is as efficient as Bactec 460 TB
      and significantly more efficient than LJ for the rapid recovery of mycobacteria
      from both pulmonary and extrapulmonary clinical specimens. Though the BACTEC 9000
      MB system is recommended for respiratory specimens, we demonstrated that it can
      be successfully used also for recovery of mycobacteria from clinical specimens
      from various extrapulmonary sites.

PMID- 9230385
TI  - Multiplex reverse transcription-PCR for surveillance of influenza A and B viruses
      in England and Wales in 1995 and 1996.
AB  - Multiple-target (multiplex) reverse transcription-PCR (RT-PCR) for detection,
      typing, and subtyping of the hemagglutinin gene of influenza type A (H3N2 and
      H1N1) and type B viruses was developed and applied prospectively to virological
      surveillance of influenza in England in the 1995-1996 winter season. During this
      season both influenza A H3N2 and H1N1 viruses were circulating, although at
      different times. Six hundred nineteen combined nose and throat swabs taken by
      general practitioners in sentinel practices from individuals presenting with
      "influenzalike illness" were analyzed by culture, multiplex RT-PCR, and
      immunofluorescence. Of the 619 samples, 246 (39.7%) were positive by multiplex RT
      PCR compared with 200 (32.3%) which yielded influenza viruses on culture. There
      was 100% correlation between multiplex RT-PCR typing and subtyping and the
      influenza types and subtypes obtained from culture. There was also excellent
      correlation between the temporal detection of influenza A H3N2 and H1N1 viruses
      by multiplex RT-PCR and by culture. During the peak weeks of influenza virus
      activity, a total of 259 specimens were received, of which 101 (38.9%) yielded
      influenza viruses on culture while 149 (57.5%) were positive in multiplex RT-PCR,
      providing an increase in detection of influenza viruses of approximately 20%. The
      increased detection of influenza virus occurred in all the age groups sampled.
      Samples which were positive by multiplex RT-PCR but negative by culture were not
      detected significantly earlier or later in the winter of 1995-1996 but were
      detected during the peak weeks of clinical influenza virus activity. Multiplex RT
      PCR was successfully used in surveillance of influenza to provide accurate,
      sensitive diagnosis directly on clinical specimens sent through the post.

PMID- 9230386
TI  - Application of the Etest to the antimicrobial susceptibility testing of
      Mycobacterium marinum clinical isolates.
AB  - Mycobacterium marinum, a well-recognized cutaneous pathogen, is usually treated
      by chemotherapy without available standardized in vitro susceptibility testing
      information. In this study, we have attempted to apply the stable-gradient method
      (Etest; AB Biodisk, Solna, Sweden) to susceptibility testing of M. marinum in
      order to assess the activities of eight antimicrobial agents against 60 recent
      clinical strains of M. marinum collected from 10 geographic sites within the
      United States. Two plated media (5% sheep blood Mueller-Hinton agar and
      Middlebrook 7H11 agar) were compared, and 7H11 agar was found to be superior in
      supporting the growth of all strains. Four reference strains of M. marinum were
      tested on five occasions with eight drugs (160 tests) in order to evaluate Etest
      reproducibility. Results were observed to be within 1 log2 dilution of the all
      test median MIC for 97.5% of the Etests. Our MIC results for the 60 strains
      clearly demonstrate the best in vitro potency against M. marinum isolates to be
      as follows (rank order): trimethoprim-sulfamethoxazole (MIC at which 90% of the
      isolates are inhibited [MIC90], 0.25 and 4.25 microg/ml, respectively) =
      ethambutol > clarithromycin (MIC90, 1 microg/ml) > minocycline = doycycline
      (MIC90, 4 microg/ml) > amikacin (MIC90, 8 microg/ml). Rifampin was only
      marginally active against the M. marinum strains tested (MIC90, at the National
      Committee for Clinical Laboratory Standards) breakpoint of 1 microg/ml), and
      ciprofloxacin was not active (MIC90, 8 microg/ml). These data should enhance the
      empiric drug selection for contemporary M. marinum infections and also provide
      evidence that the Etest can be utilized to guide chemotherapy with alternative
      agents.

PMID- 9230387
TI  - PCR amplification and comparison of nucleotide sequences from the groESL heat
      shock operon of Ehrlichia species.
AB  - Degenerate PCR primers derived from conserved regions of the eubacterial groESL
      heat shock operon were used to amplify groESL sequences of Ehrlichia equi,
      Ehrlichia phagocytophila, the agent of human granulocytic ehrlichiosis (HGE),
      Ehrlichia canis, Bartonella henselae, and Rickettsia rickettsii. The groESL
      nucleotide sequences were less conserved than the previously determined 16S rRNA
      gene sequences of these bacteria. A phylogenetic tree derived from deduced GroEL
      amino acid sequences was similar to trees based on 16S rRNA gene sequences.
      Nucleotide sequences obtained from clinical samples containing E. equi, E.
      phagocytophila, or the HGE agent were very similar (99.9 to 99.0% identity), and
      the deduced amino acid sequences were identical. Some divergence was evident
      between nucleotide sequences amplified from samples originating from the United
      States (E. equi and the HGE agent) and sequences from the European species, E.
      phagocytophila. A single pair of PCR primers derived from these sequences was
      used to detect E. chaffeensis and HGE agent DNA in blood samples from human
      patients with ehrlichiosis.

PMID- 9230388
TI  - Development of an antimicrobial susceptibility testing method suitable for
      performance during space flight.
AB  - Very little is known regarding the effects of the microgravity environment of
      space flight upon the action of antimicrobial agents on bacterial pathogens. This
      study was undertaken to develop a simple method for conducting antibacterial
      susceptibility tests during a space shuttle mission. Specially prepared
      susceptibility test research cards (bioMerieux Vitek, Hazelwood, Mo.) were
      designed to include 6 to 11 serial twofold dilutions of 14 antimicrobial agents,
      including penicillins, cephalosporins, a beta-lactamase inhibitor, vancomycin,
      erythromycin, tetracycline, gentamicin, ciprofloxacin, and trimethoprim
      sulfamethoxazole. MICs of the drugs were determined by visual reading of color
      end points in the Vitek research cards made possible by incorporation of a
      colorimetric growth indicator (alamarBlue; Accumed International, Westlake,
      Ohio). This study has demonstrated reproducible susceptibility results in the
      testing of isolates of Staphylococcus aureus, group A Streptococcus species,
      Enterococcus faecalis, Escherichia coli (beta-lactamase-positive and -negative
      strains), Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas
      aeruginosa. In some instances, the MICs were comparable to those determined by a
      standard broth microdilution method, while in some cases the unique test media
      and format yielded slightly different values that were themselves reproducible.
      The proposed in-flight experiment will include inoculation of the Vitek cards on
      the ground prior to launch of the space shuttle, storage of inoculated cards at
      refrigeration temperature aboard the space shuttle until experiment initiation,
      and then incubation of the cards for 18 to 48 h prior to visual interpretation of
      MICs by the mission's astronauts. Ground-based studies have shown reproducible
      MICs following storage of inoculated cards for 7 days at 4 to 8 degrees C to
      accommodate the mission's time schedule and the astronaut's activities. For
      comparison, ground-based control (normal gravity) MIC values will be generated by
      simultaneous inoculation and incubation of a second set of test cards in a
      laboratory at the launch site. This procedure can provide for a safe and compact
      experiment that should yield new information on the effects of microgravity on
      the biological activities of various classes of antibiotics.

PMID- 9230389
TI  - Evidence that mortality from Vibrio vulnificus infection results from single
      strains among heterogeneous populations in shellfish.
AB  - Vibrio vulnificus is the leading cause of food-related mortality reported in the
      state of Florida. It is normal microflora in marine environments, where seawater
      and molluscan shellfish are the primary vectors of V. vulnificus disease. Risk
      correlates with seasonally high numbers of V. vulnificus bacteria during the
      summer months. Currently, the infectious dose for humans, as well as whether the
      disease is caused by single or multiple strains found in molluscan shellfish, is
      unknown. In this work, we studied pulsed-field gel electrophoresis profiles of V.
      vulnificus strains isolated from blood and oysters associated with V. vulnificus
      disease. Results showed that ca. 10(3) V. vulnificus bacteria/gram of oyster and
      higher concentrations were associated with human infections and that a single V.
      vulnificus strain, evidenced by pulsed-field gel electrophoresis profiles, was
      isolated from human tissues.

PMID- 9230390
TI  - Evaluation of the Vidas Chlamydia test to detect and verify Chlamydia trachomatis
      in urogenital specimens.
AB  - The Vidas Chlamydia test (CHL) is an automated enzyme-linked immunofluorescence
      assay for the detection of Chlamydia trachomatis. Positive and equivocal results
      are confirmed with a blocking assay. A mouse monoclonal antibody directed against
      the chlamydial lipopolysaccharides was used for the test. The CHL assay is widely
      used in Europe, but U.S. experience with it is limited. Three clinical test sites
      (The Arlington Hospital, Arlington, Va., Indiana University, Indianapolis, and
      the University of California, San Francisco) compared CHL with tissue culture
      (TC) for the identification of chlamydia in urogenital specimens (2,453 females
      and 850 males). True positives (TP) were defined as either TC positive or TC
      negative and CHL positive by a positive direct fluorescent-antibody assay or PCR
      test. Overall prevalence was 5.5% for females, 10.3% for male urethral swabs, and
      10.7% for combined male TC urethral swabs and CHL with first catch urine (FCU)
      specimens. Compared to TP, CHL and TC had sensitivities of 89.6 and 94.1% with
      female cervical swabs and 90.9 and 86.4% with male urethral swabs, respectively.
      CHL sensitivity was 81.2 for male FCU specimens and 77.7% for matching male TC
      swabs. There were relatively few false-positive results, with all specificities
      being >99.4%. With the blocking assay, Vidas CHL specificity was >99.7%. However,
      male FCU specimen sensitivity was compromised because 9.2% (7 of 76) of the TP
      were initially positive but were not confirmed. An improvement in the Vidas
      blocking assay is needed before we can recommend its use with male urine.
      Alternatively, one could argue that the specificity of the test is so high that a
      confirmatory assay is not needed. For male and female swabs, the Vidas CHL assay
      has a performance that is similar to that of TC.

PMID- 9230391
TI  - Detection of group B rotaviruses in fecal samples from diarrheic calves and adult
      cows and characterization of their VP7 genes.
AB  - Groups A, B, and C rotaviruses have been identified in cattle. Group B
      rotaviruses are associated with sporadic cases of diarrhea in calves and adult
      cows. From diagnostic submissions to our laboratory, 90 fecal samples from cases
      of calf diarrhea, 81 fecal samples from cases of adult cow diarrhea (winter
      dysentery), and 20 fecal samples from case control normal adult cows were tested
      for group B rotaviruses by polyacrylamide gel electrophoresis (PAGE), and reverse
      transcription (RT)-PCR (targeting 279 bp of the VP7 gene). In addition, 53 fecal
      samples from diarrheic adult cows were tested for group B rotaviruses by immune
      electron microscopy (IEM). By RT-PCR, five samples from calves were group B
      rotavirus positive (5.6%). Fifteen samples from adult cows with diarrhea were
      group B rotavirus positive (18.5%), and none of the control fecal samples from
      normal cows were positive for group B rotaviruses. By PAGE, one calf sample (RT
      PCR positive) was group B rotavirus positive (short electropherotype), but none
      of the adult cow samples were positive for group B rotaviruses. By IEM, 5 (9.4%)
      of the 53 fecal samples from diarrheic adult cows were group B positive (all were
      also RT-PCR positive). The VP7 genes of three strains (WD653 from an adult cow
      and the ATI and Mebus calf strains) were sequenced. The VP7 genes from the three
      bovine strains showed high (over 90%) nucleotide and deduced amino acid
      homologies, but lower homologies (48 to 61%) were seen between these genes and
      the genes from rodent (IDIR) and human (ADRV) group B rotaviruses. Although there
      were some differences of degree, all inoculated gnotobiotic calves (n = 6) showed
      abnormal feces between 1 and 3 days after inoculation with each of three strains
      of group B bovine rotaviruses, and group B rotaviruse, were detected in the feces
      for up to 2 weeks by RT-PCR but for shorter periods by PAGE or IEM.

PMID- 9230392
TI  - Molecular epidemiology of Streptococcus pyogenes in an area where acute
      pharyngotonsillitis is endemic.
AB  - During an open clinical trial in an area where streptococcal infections are
      hyperendemic, we studied the genetic polymorphism of Streptococcus pyogenes
      isolates collected from patients and from healthy carriers living in close
      contact with them. The clonal diversity of isolates was analyzed by pulsed-field
      gel electrophoresis with three restriction enzymes (SmaI, ApaI, and SacII). The
      pharynx of each patient and healthy carrier was colonized by a single clone,
      suggesting the clonal nature of streptococcal colonization in individuals. Among
      52 isolates obtained from patients with acute pharyngotonsillitis, we found 14
      genetically unrelated clones, showing the genetic diversity of S. pyogenes.
      However, two clones belonging to the M1 and M12 serotypes represented about 70%
      of isolates in carriers and patients. Pharyngeal colonization in cured patients
      was monitored for 3 to 4 months. After the initial elimination of S. pyogenes
      following antibiotic therapy, the rate of recolonization was high by day 30
      (about 20%) and was also at that level between days 90 and 120; this was similar
      to the carriage rate in family contacts. Thus, cured patients can be
      recontaminated by unrelated clones, suggesting that colonization of healthy
      carriers might be a potential source of spread and redistribution of S. pyogenes
      isolates.

PMID- 9230393
TI  - Multicenter laboratory evaluation of the bioMerieux Vitek antimicrobial
      susceptibility testing system with 11 antimicrobial agents versus members of the
      family Enterobacteriaceae and Pseudomonas aeruginosa.
AB  - A four-center study in which a total of 1,082 recent clinical isolates of members
      of the family Enterobacteriaceae and Pseudomonas aeruginosa were examined versus
      11 antimicrobial agents with the bioMerieux Vitek susceptibility test system
      (Hazelwood, Mo.) and the GNS-F6 card was conducted. In addition, a challenge set
      consisting of the same 200 organisms was examined in each of the four
      participating laboratories. Results obtained with the Vitek system were compared
      to MICs determined by a standardized broth microdilution method. For purposes of
      comparison, susceptibility categories (susceptible, intermediate, or resistant)
      were assigned on the basis of the results of both methods. The result of the
      broth microdilution test was considered definitive. The total category error rate
      with the Vitek system and the recent clinical isolates (11,902 organism
      antimicrobial comparisons) was 4.5%, i.e., 1.7% very major errors, 0.9% major
      errors, and 1.9% minor errors. The total category error rate calculated from
      tests performed with the challenge set (i.e., 8,800 organism-antimicrobial
      comparisons) was 5.9%, i.e., 2.2% very major errors, 1.1% major errors, and 2.6%
      minor errors. Very major error rates higher than the totals were noted with
      Enterobacter cloacae versus ampicillin-sulbactam, aztreonam, ticarcillin, and
      ticarcillin-clavulanate and with P. aeruginosa versus mezlocillin, ticarcillin,
      and ticarcillin-clavulanate. Major error rates higher than the averages were
      observed with Proteus mirabilis versus imipenem and with Klebsiella pneumoniae
      versus ofloxacin. Excellent overall interlaboratory reproducibility was observed
      with the Vitek system. The importance of inoculum size as a primary determinant
      in the accuracy of susceptibility test results with the Vitek system was clearly
      demonstrated in this study. Specifically, when an inoculum density fourfold
      higher than that recommended by the manufacturer was used, high rates of false
      resistance results were obtained with cell wall-active antimicrobial agents
      versus both the Enterobacteriaceae and P. aeruginosa.

PMID- 9230394
TI  - Coinfection with Bartonella clarridgeiae and Bartonella henselae and with
      different Bartonella henselae strains in domestic cats.
AB  - Bartonella clarridgeiae and several strains of Bartonella henselae, the agent of
      cat scratch disease, with variations in the 16S rRNA gene have been found to
      infect the blood of cats. An epidemiologic study of Bartonella infection in
      domestic French cats revealed that of 436 cats sampled, 5 cats (1.1%) were
      coinfected with B. henselae and B. clarridgeiae and 2 cats (0.5%) were coinfected
      with two strains of B. henselae with variations in the 16S rRNA gene, B. henselae
      type I and type II. In an indirect immunofluorescence assay, coinfected cats
      tested positive for both Bartonella species at titers of > or = 128.
      Identification of the colonies was achieved by preformed enzyme analysis, PCR
      restriction fragment length polymorphism analysis of the citrate synthase gene,
      and 16S rRNA gene sequencing. Colony size differences in mixed culture allowed
      differentiation of the Bartonella species. The coinfection of cats with two
      Bartonella species or variants of the same species raises concern about the
      possibility of dual infection in humans. The development of a polyvalent vaccine
      targeted against the most pathogenic or invasive strains may be a means of
      protecting cats and man from infection.

PMID- 9230395
TI  - Detection and identification of mycobacteria by amplification of RNA and DNA in
      pretreated blood and bone marrow aspirates by a simple lysis method.
AB  - A sodium dodecyl (lauryl) sulfate method was evaluated for the preparation of
      blood specimens and bone marrow aspirates for use in two amplification procedures
      (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test [AMTDT] and Roche
      Amplicor M. avium/M. intracellulare [MAI] Test) for the detection and
      identification of Mycobacterium tuberculosis and M. avium and M. intracellulare,
      respectively. The AMTDT is based on amplification of rRNA, whereas the Amplicor
      MAI Test amplifies a specific DNA region of the 16S rRNA gene. The results of
      amplification techniques were compared with those of standard culture and culture
      in BACTEC 13A and BACTEC 12B liquid media. A total of 121 blood specimens and 15
      bone marrow aspirates were collected from 136 AIDS patients. Mycobacterial growth
      was recovered for 103 specimens; 35 yielded M. tuberculosis, 62 yielded M. avium,
      5 yielded M. genavense, and 1 yielded M. kansasii. The values of sensitivity and
      specificity in pretreated specimens for detection of M. tuberculosis by the AMTDT
      were 94.3 and 100%, respectively, and those for detection of M. avium by the
      Amplicor MAI Test were 91.9 and 100%, respectively. The simple lysis method
      described in the present work allows the recovery of mycobacteria from blood
      specimens and bone marrow aspirates and may be used in combination with the AMTDT
      and the Amplicor MAI Test to detect and identify different members of the genus
      Mycobacterium. This method might also be applicable for the identification of
      mycobacteria from blood culture fluids with acridinium-ester-labeled DNA probes.

PMID- 9230397
TI  - Diagnosis of genitourinary Chlamydia trachomatis infections by using the ligase
      chain reaction on patient-obtained vaginal swabs.
AB  - We compared the ligase chain reaction (LCR) assay to cell culture for diagnosis
      of genitourinary chlamydial infections in women using swab specimens obtained by
      clinicians from the endocervix and by patients from their own vaginas. Specimens
      from 40 (12.9%) of 309 patients were positive for chlamydial infection by
      culture, while the specimens of 50 (16.2%) patients were positive by LCR.
      Chlamydia trachomatis infection was verified for 9 of 10 patients whose LCR
      specimens were positive but whose cultures were negative. Vaginal and cervical
      swab specimens were positive by LCR for 46 (93.9%) and 44 (89.8%) of 49 chlamydia
      infected patients, respectively. These data suggest that LCR testing for
      chlamydia with vaginal swab specimens obtained by patients themselves is as
      sensitive as cervical LCR and more sensitive than cell culture.

PMID- 9230396
TI  - Diagnosis of Neisseria gonorrhoeae infections in women by using the ligase chain
      reaction on patient-obtained vaginal swabs.
AB  - The increased sensitivities of nucleic acid amplification tests such as ligase
      chain reaction (LCR) have the potential to simplify specimen collection for
      gonorrhea diagnosis. In this study patients took their own vaginal swab specimens
      for gonorrhea culture and LCR testing. Immediately following specimen collection
      by patients, a trained clinician obtained endocervical swab specimens for the
      same tests. By using LCR to diagnose gonorrhea, 54 (17.5%) of 309 patients had
      positive tests. Forty-five patients with positive cervical LCR tests also had
      positive vaginal LCR tests; for one patient, only a cervical LCR specimen was
      positive, and for eight patients, only vaginal specimens were positive. For
      specimens from patients whose gonorrhea cultures were positive, all vaginal swab
      specimens were positive by LCR and 42 (91%) of 46 cervical swab specimens were
      positive by LCR. LCR-positive specimens from eight patients with negative
      cultures (four with positive vaginal specimens only, one with a positive cervical
      specimen only, and three with positive vaginal and cervical specimens) were
      further evaluated with unrelated probe sets for gonococcal pilin B. Following
      resolution of the discrepancies between culture-negative and LCR-positive
      specimens, a diagnosis of gonorrhea could be confirmed for 52 of 54 patients with
      positive LCR tests. LCR testing with vaginal swabs was 100% sensitive and 99.6%
      specific and had a positive predictive value of 98.1% and a negative predictive
      value of 100%. In this study LCR testing of vaginal swab specimens obtained by
      patients themselves was significantly more sensitive for gonorrhea diagnosis of
      women than cervical LCR or culture (100% versus 84.6% for cervical LCR or
      culture; Mantel-Haenszel chi-square test result, 8.58; P = 0.003).

PMID- 9230398
TI  - Maxillary sinusitis caused by Pleurophomopsis lignicola.
AB  - An immunocompetent 59-year-old man developed sinusitis over a 6- to 8-month
      period after cutting down a rotted maple tree (Acer sp.). A polypoid obstruction
      with a bloody drainage was evident in his right nasal cavity. A computed
      tomographic scan showed an opacification of the maxillary sinus. Surgery was
      performed to remove a fungus ball that had extended into the patient's medial
      sinus cavity. Sections of the sinonasal mucosa revealed marked acute and chronic
      sinusitis with inflammation, congestion, and hemorrhage. Sections from the pasty
      brown to black debrided material revealed a fungus ball consisting of an
      extensive network of brown-pigmented, septate, profusely branched hyphae. When
      grown on oat agar, the phaeoid fungus produced pycnidia and was identified as
      Pleurophomopsis lignicola. The genus Pleurophomopsis includes seven species,
      which are all known from plant material. This report documents for the first time
      a coelomycetous fungus, P. lignicola, causing sinusitis in an immunocompetent
      patient.

PMID- 9230399
TI  - Pretreatment of clinical specimens with sodium dodecyl (lauryl) sulfate is not
      suitable for the mycobacteria growth indicator tube cultivation method.
AB  - When using the Mycobacteria Growth Indicator Tube (MGIT), pretreatment of
      clinical specimens with N-acetyl-L-cysteine-NaOH is recommended by the
      manufacturer. Processing of clinical specimens (n = 1,000) with sodium dodecyl
      (lauryl) sulfate-NaOH resulted in both poor recovery and delayed mean time to
      detection of acid-fast bacilli. Values were comparable to those obtained on solid
      media.

PMID- 9230400
TI  - Identification of a new strain of fastidious enterovirus 70 as the causative
      agent of an outbreak of hemorrhagic conjunctivitis.
AB  - A 1994 outbreak of acute hemorrhagic conjunctivitis in Israel was caused by an
      enterovirus 70 strain that was distinct from previously reported strains.
      Characterization was by electron microscopy (eye washes), reverse transcription
      PCR (RT-PCR; eyewash, specimens, eye swabs, and tears), and sequence analysis of
      RT-PCR-amplified fragments from the 5' noncoding region and VP1.

PMID- 9230401
TI  - A case of peritonitis caused by Roseomonas gilardii in a patient undergoing
      continuous ambulatory peritoneal dialysis.
AB  - A case of peritonitis caused by Roseomonas gilardii in a patient receiving
      continuous ambulatory peritoneal dialysis is presented. The patient's domestic
      water supply was implicated as the probable source of infection. This is the
      first report of R. gilardii causing such an infection.

PMID- 9230402
TI  - Frequency of isolation of Staphylococcus intermedius from humans.
AB  - We collected 3,397 consecutive isolates of coagulase-positive staphylococci from
      various specimens of hospitalized patients. All were retrospectively classified
      as Staphylococcus aureus, except two which were identified as S. intermedius: one
      isolated from the nasal flora of a healthy carrier and the other isolated from
      pleural fluid, probably as a sample contaminant.

PMID- 9230403
TI  - Simple color tests based on an alanyl peptidase reaction which differentiate
      Listeria monocytogenes from other Listeria species.
AB  - The hydrolysis of DL-alanine-beta-naphthylamide and D-alanine-p-nitroanilide for
      identification of Listeria spp. has been studied with 227 cultures. All species
      of Listeria, except L. monocytogenes, hydrolyzed these substrates. The reactions
      were detected by simple chromogenic reactions and could substitute for the CAMP
      test.

PMID- 9230404
TI  - Evaluation of a rapid air thermal cycler for detection of Mycobacterium
      tuberculosis.
AB  - The Air Thermal Cycler (ATC) (Idaho Technology, Idaho Falls, Idaho) utilizes the
      unique technology of small-volume glass capillary tubes and high-velocity air for
      the heating and cooling medium for the PCR. Standard heat block thermal cycler
      (HBTC) and ATC performance characteristics were compared for the detection of
      Mycobacterium tuberculosis. Sensitivity was 100% for all smear-positive, M.
      tuberculosis culture-positive specimens for both the HBTC and the ATC. Of smear
      negative, M. tuberculosis culture-positive specimens, sensitivity was 42.9% with
      the HBTC and 22.0% with the ATC. Specificity was 100% for both assay systems.
      Total assay time was 6.5 and 4 h and the reagent cost was 84 and 32 cents for the
      HBTC and ATC, respectively. The ATC offered an excellent alternative to the
      traditional HBTC for diagnosis of M. tuberculosis in smear-positive specimens by
      PCR.

PMID- 9230406
TI  - Emergence of Clostridium botulinum type B-like nontoxigenic organisms in a
      patient with type B infant botulism.
AB  - We encountered a patient with infant botulism caused by a single clone of
      Clostridium botulinum type B. In the early convalescent phase, a C. botulinum
      type B-like nontoxigenic organism emerged in the feces instead. Growth inhibition
      of toxigenic strains by nontoxigenic strains was examined.

PMID- 9230405
TI  - Characterization of a neurotoxigenic Clostridium butyricum strain isolated from
      the food implicated in an outbreak of food-borne type E botulism.
AB  - Neurotoxigenic Clostridium butyricum was isolated from the food implicated in an
      outbreak of clinically diagnosed type E botulism in China. PCR assay showed that
      the isolate (LCL 155) contained the type E botulinum toxin gene. This appears to
      be the first report of neurotoxigenic C. butyricum causing food-borne botulism.

PMID- 9230407
TI  - Laboratory diagnosis of respiratory virus infections in 24 hours by utilizing
      shell vial cultures.
AB  - Immunofluorescence staining of centrifugation-enhanced shell vial (SV) cultures
      for respiratory viruses (RV) after 24 h of incubation, rather than the more
      commonly prescribed times of 48 h and 5 days, allowed for the detection of 77% of
      the RV-positive specimens that would ordinarily not have been detected as
      positive until 48 h. Staining SVs at 24 h also permitted earlier detection of
      viruses that were missed by rapid antigen detection methods.

PMID- 9230408
TI  - Invasive amoebiasis in two patients with AIDS and cytomegalovirus colitis.
AB  - Homosexual persons or human immunodeficiency virus (HIV)-infected patients
      frequently excrete cysts of nonpathogenic strains of Entamoeba histolytica
      ("Entamoeba dispar"). However, invasive amoebiasis is rare. We report two
      patients with AIDS and cytomegalovirus colitis in whom invasive amoebiasis was
      histologically diagnosed. It is concluded that E. histolytica has to be
      considered in HIV-infected patients with colitis.

PMID- 9230409
TI  - Evaluation of the AnaeroPack system for growth of anaerobic bacteria.
AB  - Growth of anaerobic bacteria in the AnaeroPack (Mitsubishi Gas Chemical America,
      Inc., New York, N.Y.) anaerobic atmosphere generation systems, both the
      AnaeroPack jar and pouch and the AnaeroPack in a GasPak jar were considered
      equivalent to or better than growth obtained in the corresponding GasPak jar or
      pouch system (Becton Dickinson Microbiology Systems, Cockeysville, Md.) for 89
      (86%) of the 103 anaerobes tested. There were a total of 26 discrepancies after
      48 h of incubation, with 16 discrepancies unresolved after 96 h of incubation.
      The AnaeroPack jar and pouch never failed to reduce the anaerobic indicator. The
      AnaeroPack systems are easy to use and performed at least as well as or better
      than the BBL GasPak systems for growth of anaerobic bacteria.

PMID- 9230411
TI  - Indwelling device-related bacteremia caused by serum-susceptible Campylobacter
      coli.
AB  - Two isolates of serum-susceptible Campylobacter coli were recovered in a 7-day
      interval from blood from a patient with hepatocellular carcinoma and liver
      cirrhosis whose peritoneal-caval (Denver's) shunt malfunctioned. Identical random
      amplified polymorphic DNA fingerprints, cellular fatty acid chromatograms, and
      antibiograms of the two isolates indicate that C. coli has the ability to cause
      catheter-related bacteremia following its colonization of the catheter.

PMID- 9230410
TI  - Pediatric bacteremia due to Staphylococcus warneri: microbiological,
      epidemiological, and clinical features.
AB  - Between 1991 and 1995, an apparent high rate of Staphylococcus warneri
      bacteremias at the Royal Children's Hospital, Melbourne, Victoria, Australia,
      raised the possibility of a virulent nosocomial strain. In a retrospective review
      of 30 S. warneri bacteremias in children, organisms were viable and verified in
      22 episodes, 12 representing significant bacteremias. Of these 12 episodes, 2
      pairs shared chromosomal DNA pulsed-field gel electrophoresis patterns in
      unconnected patients, dispelling concerns about a single virulent strain.

PMID- 9230412
TI  - Detection of equine arteritis virus in the semen of carrier stallions by using a
      sensitive nested PCR assay.
AB  - A nested PCR, developed for the detection of equine arteritis virus (EAV) in
      semen, detected less than 2.5 PFU of EAV per ml of naturally infected seminal
      plasma. Based on results from testing 88 semen samples from 70 stallions, the
      sensitivity and specificity of the test were 100 and 97%, respectively.

PMID- 9230414
TI  - Dilution of samples collected and transported for Gen-Probe PACE 2 processing
      facilitates detection of Chlamydia trachomatis by Roche Amplicor PCR.

PMID- 9230413
TI  - Prevalence of bacterial resistance to quinolones and other antimicrobials among
      avian Escherichia coli strains isolated from septicemic and healthy chickens in
      Spain.
AB  - Antimicrobial therapy is an important tool in reducing the enormous losses in the
      poultry industry caused by Escherichia coli infections (colibacillosis). However,
      resistance to existing antimicrobials is widespread and of concern to poultry
      veterinarians. Antimicrobial resistance testing of 468 avian E. coli strains
      isolated in Spain showed very high levels of resistance to trimethoprim
      sulfamethoxazole (67%) and the new fluoroquinolones (13 to 24%). As these
      antimicrobial agents may cause cross-resistance with human enteric pathogens,
      prudent use of them in veterinary medicine is highly recommended.

PMID- 9230415
TI  - Detection of anti-Toxoplasma immunoglobulin M in pregnant women.

PMID- 9230416
TI  - The practical use of PCR for rapid detection of methicillin resistance among
      staphylococcal clinical isolates from Turkish hospitals.

PMID- 9230417
TI  - Two cheers for the multilateral malaria initiative.

PMID- 9230418
TI  - Canada wins biotech boost of cancer vaccine project.

PMID- 9230419
TI  - Japan's life sciences take integrated road.

PMID- 9230420
TI  - Clinton backs Congressional efforts on genetic discrimination.

PMID- 9230421
TI  - NIH urged to address chimp care 'crisis'.

PMID- 9230422
TI  - Malaria meeting charts rocky path ahead.

PMID- 9230423
TI  - Limit the number of grants per person.

PMID- 9230424
TI  - A molecular handle on the Neanderthals.

PMID- 9230425
TI  - Spongiform encephalopathies. Tracking turncoat prion proteins.

PMID- 9230426
TI  - Symbiosis. Making light work of adaptation.

PMID- 9230427
TI  - Immunodeficiency viruses. Spoilt for choice of co-receptors.

PMID- 9230428
TI  - Familial Parkinson's disease. The awakening of alpha-synuclein.

PMID- 9230429
TI  - Fatigue, alcohol and performance impairment.

PMID- 9230430
TI  - Metallothionein in snail Cd and Cu metabolism.

PMID- 9230431
TI  - A new SIV co-receptor, STRL33.

PMID- 9230432
TI  - A multivalent PDZ-domain protein assembles signalling complexes in a G-protein
      coupled cascade.
AB  - How are signalling molecules organized into different pathways within the same
      cell? In Drosophila, the inaD gene encodes a protein consisting of five PDZ
      domains which serves as a scaffold to assemble different components of the
      phototransduction cascade, including the principal light-activated ion channels,
      the effector phospholipase C-beta and protein kinase C. Null inaD mutants have a
      dramatically reorganized subcellular distribution of signalling molecules, and a
      total loss of transduction complexes. Also, mutants defective in a single PDZ
      domain produce signalling complexes that lack the target protein and display
      corresponding defects in their physiology. A picture emerges of a highly
      organized unit of signalling, a 'transduclisome', with PDZ domains functioning as
      key elements in the organization of transduction complexes in vivo.

PMID- 9230433
TI  - A high deuterium abundance at redshift z = 0.7.
AB  - Of the light elements, the primordial abundance of deuterium relative to
      hydrogen, (D/H)p, provides the most sensitive diagnostic for the cosmological
      mass density parameter, omegaB. Recent high-redshift D/H measurements are highly
      discrepant, although this may reflect observational uncertainties. The larger
      primordial D/H values imply a low omegaB (requiring the Universe to be dominated
      by non-baryonic matter), and cause problems for galactic chemical evolution
      models, which have difficulty in reproducing the steep decline in D/H to the
      present-day values. Conversely, the lower D/H values measured at high redshift
      imply an omegaB greater than that derived from 7Li and 4He abundance
      measurements, and may require a deuterium-abundance evolution that is too low to
      easily explain. Here we report the first measurement of D/H at intermediate
      redshift (z = 0.7010), in a gas cloud selected to minimize observational
      uncertainties. Our analysis yields a value of D/H ((2.0 +/- 0.5) x 10[-4]) which
      is at the upper end of the range of values measured at high redshifts. This
      finding, together with other independent observations, suggests that there may be
      inhomogeneity in (D/H)p of at least a factor of ten.

PMID- 9230434
TI  - Landscape ecology of algal symbionts creates variation in episodes of coral
      bleaching.
AB  - Reef-building corals are obligate, mutualistic symbioses of heterotrophic animals
      and phototrophic dinoflagellates (Symbiodinium spp.). Contrary to the earlier,
      widely accepted belief that corals harbour only one symbiont, we found that the
      ecologically dominant Caribbean corals Montastraea annularis and M. faveolata can
      act as hosts to dynamic, multi-species communities of Symbiodinium. Composition
      of these communities follows gradients of environmental irradiance, implying that
      physiological acclimatization is not the only mechanism by which corals cope with
      environmental heterogeneity. The importance of this diversity was underlined by
      analysis of a natural episode of coral bleaching. Patterns of bleaching could be
      explained by the preferential elimination of a symbiont associated with low
      irradiance from the brightest parts of its distribution. Comparative analyses of
      symbionts before and after bleaching from the same corals supported this
      interpretation, and suggested that some corals were protected from bleaching by
      hosting an additional symbiont that is more tolerant of high irradiance and
      temperature. This 'natural experiment' suggests that temporal and spatial
      variability can favour the coexistence of diverse symbionts within a host,
      despite the potential for destabilizing competition among them.

PMID- 9230435
TI  - Multistability of cognitive maps in the hippocampus of old rats.
AB  - Hippocampal neurons provide a population code for location. In young rats,
      environments are reliably 'mapped' by groups of neurons that have firing
      locations ('place fields') that can be stable for several months. Old animals
      exhibit deficits in spatial memory, raising the question of whether the quality
      or stability of their hippocampal 'cognitive maps' is altered. By recording from
      large groups of neurons, we observed the hippocampal spatial code to be
      multistable. In young rats, the place field maps were reliable both within and
      between episodes in a familiar environment. In old rats, place field maps were
      accurate and stable during an episode, but frequently exhibited complete
      rearrangements between episodes. In a spatial memory task, both young and old
      rats exhibited bimodal performance, consistent with map multistability early in
      training. However, the performance of young rats became almost unimodal with
      further training, whereas that of old rats remained markedly bimodal. The
      multistability of the hippocampal map provides an insight into the dynamics of
      neural coding in high-level cortical structures and their changes during ageing,
      and may provide an explanation for the frequent failure of place recognition in
      elderly humans.

PMID- 9230436
TI  - cAMP-induced switching in turning direction of nerve growth cones.
AB  - Development of the nervous system depends on the correct pathfinding and target
      recognition by the growing tip of an axon, the growth cone. Diffusible or
      substrate-bound molecules present in the environment may serve as either
      attractants or repellents to influence the direction of growth-cone extension.
      Here we report that differences in cyclic-AMP-dependent activity in a neuron may
      result in opposite turning of the growth cone in response to the same guidance
      cue. A gradient of brain-derived neurotrophic factor normally triggers an
      attractive turning response of the growth cone of Xenopus spinal neurons in
      culture, but the same gradient induces repulsive turning of these growth cones in
      the presence of a competitive analogue of cAMP or of a specific inhibitor of
      protein kinase A. This cAMP-dependent switch of the turning response was also
      found for turning induced by acetylcholine, but not for the turning induced by
      neurotrophin-3 (NT-3). Thus, in the presence of other factors that modulate
      neuronal cAMP-dependent activity, the same guidance cue may trigger opposite
      turning behaviours of the growth cone during its pathfinding in the nervous
      system.

PMID- 9230437
TI  - Synapse specificity of long-term potentiation breaks down at short distances.
AB  - Long-term potentiation (LTP), the long-lasting increase in synaptic transmission,
      has been proposed to be a cellular mechanism essential for learning and memory,
      neuronal development, and circuit reorganization. In the original theoretical and
      experimental work it was assumed that only synapses that had experienced
      concurrent pre- and postsynaptic activity are subject to synaptic modification.
      It has since been shown, however, that LTP is also expressed in synapses on
      neighbouring neurons that have not undergone the induction procedure. Yet, it is
      still believed that this spread of LTP is limited to adjacent postsynaptic cells,
      and does not occur for synapses on neighbouring input fibres. However, for
      technical reasons, tests for 'input specificity' were always done for synapses
      relatively far apart. Here we have used a new local superfusion technique, which
      allowed us to assess the synaptic specificity of LTP with a spatial resolution of
      approximately 30 microm. Our results indicate that there is no input specificity
      at a distance of less than 70 microm. Synapses in close proximity to a site of
      potentiation are also potentiated regardless of their own history of activation,
      whereas synapses far away show no potentiation.

PMID- 9230438
TI  - Molecular assessment of the potential transmissibilities of BSE and scrapie to
      humans.
AB  - More than a million cattle infected with bovine spongiform encephalopathy (BSE)
      may have entered the human food chain. Fears that BSE might transmit to man were
      raised when atypical cases of Creutzfeldt-Jakob disease (CJD), a human
      transmissible spongiform encephalopathy (TSE), emerged in the UK. In BSE and
      other TSE diseases, the conversion of the protease-sensitive host prion protein
      (PrP-sen) to a protease-resistant isoform (PrP-res) is an important event in
      pathogenesis. Biological aspects of TSE diseases are reflected in the
      specificities of in vitro PrP conversion reactions. Here we show that there is a
      correlation between in vitro conversion efficiencies and known transmissibilities
      of BSE, sheep scrapie and CJD. On this basis, we used an in vitro system to gauge
      the potential transmissibility of scrapie and BSE to humans. We found limited
      conversion of human PrP-sen to PrP-res driven by PrP-res associated with both
      scrapie (PrP[Sc]) and BSE (PrP[BSE]). The efficiencies of these heterologous
      conversion reactions were similar but much lower than those of relevant
      homologous conversions. Thus the inherent ability of these infectious agents of
      BSE and scrapie to affect humans following equivalent exposure may be finite but
      similarly low.

PMID- 9230439
TI  - A minK-HERG complex regulates the cardiac potassium current I(Kr).
AB  - MinK is a widely expressed protein of relative molecular mass approximately 15K
      that forms potassium channels by aggregation with other membrane proteins. MinK
      governs ion channel activation, regulation by second messengers, and the function
      and structure of the ion conduction pathway. Association of minK with a channel
      protein known as KvLQT1 produces a voltage-gated outward K+ current (I[sK])
      resembling the slow cardiac repolarization current (I[Ks]). HERG, a human
      homologue of the ether-a-go-go gene of the fruitfly Drosophila melanogaster,
      encodes a protein that produces the rapidly activating cardiac delayed rectifier
      (I[Kr]). These two potassium currents, I(Ks) and I(Kr), provide the principal
      repolarizing currents in cardiac myocytes for the termination of action
      potentials. Although heterologously expressed HERG channels are largely
      indistinguishable from native cardiac I(Kr), a role for minK in this current is
      suggested by the diminished I(Kr) in an atrial tumour line subjected to minK
      antisense suppression. Here we show that HERG and minK form a stable complex, and
      that this heteromultimerization regulates I(Kr) activity. MinK, through the
      formation of heteromeric channel complexes, is thus central to the control of the
      heart rate and rhythm.

PMID- 9230440
TI  - P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane
      protein and complement-receptor 1.
AB  - The factors determining disease severity in malaria are complex and include host
      polymorphisms, acquired immunity and parasite virulence. Studies in Africa have
      shown that severe malaria is associated with the ability of erythrocytes infected
      with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form
      rosettes. The molecular basis of resetting is not well understood, although a
      group of low-molecular-mass proteins called rosettins have been described as
      potential parasite ligands. Infected erythrocytes also bind to endothelial cells,
      and this interaction is mediated by the parasite-derived variant erythrocyte
      membrane protein PfEMP1, which is encoded by the var gene family. Here we report
      that the parasite ligand for rosetting in a P. falciparum clone is PfEMP1,
      encoded by a specific var gene. We also report that complement-receptor 1 (CR1)
      on erythrocytes plays a role in the formation of rosettes and that erythrocytes
      with a common African CR1 polymorphism (S1(a-)) have reduced adhesion to the
      domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive
      function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans
      that influence the interaction between erythrocytes and PfEMP1 may protect
      against severe malaria.

PMID- 9230441
TI  - Expression cloning of new receptors used by simian and human immunodeficiency
      viruses.
AB  - Several members of the chemokine-receptor family serve, in conjunction with CD4,
      as receptors for the entry of human immunodeficiency virus type I (HIV-1) into
      cells. The principal receptor for entry of macrophage-tropic (M-tropic) HIV-1
      strains is CCR5, whereas that for T-cell-line-tropic (T-tropic) strains is CXCR4.
      Unlike HIV-1, infection with either M-tropic or T-tropic strains of simian
      immunodeficiency virus (SIV) can be mediated by CCR5, but not CXCR4. SIV strains
      will also infect CD4+ cells that lack CCR5, which suggests that these strains use
      as yet unidentified receptors. Here we use an expression-cloning strategy to
      identify SIV receptors and have isolated genes encoding two members of the seven
      transmembrane G-protein-coupled receptor family that are used not only by SIVs,
      but also by strains of HIV-2 and M-tropic HIV-1. Both receptors are closely
      related to the chemokine-receptor family and are expressed in lymphoid tissues.
      One of the receptors is also expressed in colon and may therefore be important in
      viral transmission. Usage of these new receptors following experimental infection
      of non-human primates with SIV strains may provide important insight into viral
      transmission and the mechanisms of SIV- and HIV-induced acquired immune
      deficiency syndrome.

PMID- 9230442
TI  - X-linked IAP is a direct inhibitor of cell-death proteases.
AB  - The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved
      role in regulating programmed cell death in animals ranging from insects to
      humans. Ectopic expression of human IAP proteins can suppress cell death induced
      by a variety of stimuli, but the mechanism of this inhibition was previously
      unknown. Here we show that human X-chromosome-linked IAP directly inhibits at
      least two members of the caspase family of cell-death proteases, caspase-3 and
      caspase-7. As the caspases are highly conserved throughout the animal kingdom and
      are the principal effectors of apoptosis, our findings suggest how IAPs might
      inhibit cell death, providing evidence for a mechanism of action for these
      mammalian cell-death suppressors.

PMID- 9230443
TI  - Drosophila Mad binds to DNA and directly mediates activation of vestigial by
      Decapentaplegic.
AB  - The TGF-beta (transforming growth factor-beta)-related signalling proteins,
      including Decapentaplegic (Dpp) in Drosophila-and bone morphogenic proteins and
      activin in vertebrates, affect the growth and patterning of a great variety of
      structures. However, the mechanisms by which these ligands regulate gene
      expression are not understood. Activation of complexes of type I with type II
      receptors results in the phosphorylation and nuclear localization of members of
      the SMAD protein family, which are thought to act as co-activators of
      transcription, perhaps in conjunction with sequence-specific cofactors. Here we
      show that the amino-terminal domain of the Drosophila Mothers against dpp protein
      (Mad), a mediator of Dpp signalling, possesses a sequence-specific DNA-binding
      activity that becomes apparent when carboxy-terminal residues are removed. Mad
      binds to and is required for the activation of an enhancer within the vestigial
      wing-patterning gene in cells across the entire developing wing blade. Mad also
      binds to Dpp-response elements in other genes. These results suggest that Dpp
      signalling regulates gene expression by activating Mad binding to target gene
      enhancers.

PMID- 9230444
TI  - Influence of acetaminophen treatment and hydrogen peroxide treatment on the
      release of a CINC-related protein and TNF-alpha from rat hepatocyte cultures.
AB  - Western blot analysis of conditioned media from hepatocytes exposed to H2O2
      revealed that a 28 kDa protein was released dose-dependently in response to 1-10
      mM H2O2. The 28 kDa protein was present in freshly isolated hepatocytes and
      exhibited cross-reactivity towards an antibody against CINC/gro. The
      intracellular amount of the protein decreased in parallel to the H2O2-induced
      release into the medium. The CINC-related protein was absent in media harvested
      after 1 h of treatment. The delivery of CINC-related protein correlated with the
      extent of cell damage as judged from lactate dehydrogenase leakage. Likewise,
      exposure of hepatocytes to 10-50 mM acetaminophen resulted in a dose-dependent
      release of the CINC-related protein after 24 h of culture. In contrast, monomeric
      CINC (molecular weight approximately 6.5 kDa) but not the 28 kDa CINC-related
      protein was released by lipopolysaccharide (LPS)-stimulated Kupffer cells. The
      amount of monomeric CINC liberated by Kupffer cells was diminished upon
      acetaminophen-treatment. Also, the release of tumor necrosis factor-alpha by
      hepatocytes was reduced after exposure to high acetaminophen doses (40-50 mM). In
      contrast to this finding, TNF-alpha release from hepatocyte cultures was not
      affected after H2O2 treatment. These data suggest that damaged hepatocytes
      release proinflammatory cytokines which may aggravate liver injury through
      activation of neutrophils and monocytes. The results indicate that the appearance
      of the CINC-related protein is due to impairment of plasma membrane integrity as
      the consequence of massive cell damage. In addition, APAP inhibited the release
      of monomeric CINC from LPS-activated Kupffer cells and of TNF-alpha from
      hepatocytes even at concentrations that were not sufficient to affect cell
      viability.

PMID- 9230445
TI  - Role of bile salts in colchicine-induced hepatotoxicity. Implications for
      hepatocellular integrity and function.
AB  - Colchicine, a microtubule-disrupting agent, induces hepatotoxicity in
      experimental animals at the doses commonly employed to explore vesicular
      transport in the liver. The effect of manipulations of the bile salt pool on
      colchicine-induced hepatotoxicity was studied in rats to determine the role of
      bile salts in this phenomenon. Leakage of enzyme markers of liver-cell damage
      into plasma and bile induced by colchicine pre-treatment displayed a sigmoidal
      log dose-effect curve, the half-maximal effect being reached at 0.12 micromol per
      100 g body wt. Lumicolchicine, instead, showed no harmful effect. Maximal
      increment of biliary LDH discharge induced by colchicine was reduced from 950 +/-
      124% to 216 +/- 29% by bile diversion leading to a marked reduction in bile salt
      output, and this parameter was further decreased to 100 +/- 13% and 157 +/- 39%
      by subsequent repletion of the bile salt pool with the hydrophilic bile salts
      taurodehydrocholate and tauroursodeoxycholate, respectively. Conversely, infusion
      of taurocholate into non-bile salt depleted, colchicine-treated rats led to
      cholestasis and massive discharge of enzymes into both blood and bile. Our data
      show conclusively that colchicine-induced hepatotoxicity depends on the magnitude
      and composition of the bile salt flux traversing the liver. They also support the
      view that functional integrity of vesicular mechanisms presumably involved in
      membrane repair are indispensable to protect the hepatocytes from the damaging
      effect of bile salts during normal bile formation.

PMID- 9230446
TI  - Gadolinium chloride reduces cytochrome P450: relevance to chemical-induced
      hepatotoxicity.
AB  - The Kupffer cell inhibitor, gadolinium chloride (GdCl3), protects the liver from
      a number of toxicants that require biotransformation to elicit toxicity (i.e. 1,2
      dichlorobenzene and CCl4), as well as compounds that do not (i.e. cadmium
      chloride and beryllium sulfate). The mechanism of this protection is thought to
      result from reduced secretion of inflammatory and cytotoxic products from Kupffer
      cells (KC). However, since other lanthanides have been shown to decrease
      cytochrome P450 (P450) activity, the following studies were designed to determine
      if GdCl3 pretreatment alters hepatic P450 levels or activity. The toxicological
      relevance of GdCl3-mediated alterations in P450 activity was also estimated by
      determining the effect of GdCl3 pretreatment on the susceptibility of primary
      cultured hepatocytes to CCl4 and cadmium chloride (CdCl2). Male and female
      Sprague-Dawley rats were given GdCl3 (i.v., 10 mg/kg). Twenty-four hours later,
      livers were either processed for preparation of microsomes or for primary
      cultures of hepatocytes. Gadolinium chloride treatment reduced total hepatic
      microsomal P450 as well as aniline hydroxylase activity by approximately 30% in
      males and 20% in females. In hepatocytes isolated from rats pretreated with
      GdCl3, the toxicity caused by CCl4, but not CdCl2 was reduced. Interestingly,
      when GdCl3 was administered in vitro to microsomes, there was no effect on either
      the microsomal P450 difference spectra or p-hydroxylation of aniline. However,
      when GdCl3 was incubated with isolated hepatocytes, the cytotoxicity of CCl4 (but
      not CdCl2) was partially attenuated. These results suggest that, in addition to
      its inhibitory effects on KC, GdCl3 produces other effects which may alter the
      susceptibility of hepatocytes to toxicity caused by certain chemicals.

PMID- 9230447
TI  - Suppression of Kupffer cell function prevents cadmium induced hepatocellular
      necrosis in the male Sprague-Dawley rat.
AB  - Exposure of humans to toxic metals and metalloids is a major environmental
      problem. Many metals, such as cadmium, can be hepatotoxic. However, the
      mechanisms by which metals cause acute hepatic injury are in many cases unknown.
      Previous reports suggest a major role for inflammation in acute cadmium induced
      hepatotoxicity. In initial experiments we found that a non-hepatotoxic dose of
      cadmium chloride (CdCl2; 2.0 mg/kg, i.v.) markedly increased the clearance rate
      of colloidal carbon from the blood, which is indicative of enhanced phagocytic
      activity by Kupffer cells (resident hepatic macrophages). Thus. the objective
      these studies was to determine the involvement of Kupffer cells in cadmium
      induced liver injury by inhibiting their function with gadolinium chloride
      (GdCl3). Male Sprague-Dawley rats were administered GdCl3 (10 mg/kg, i.v.)
      followed 24 h later by a single dose of CdCl2 (3.0 and 4.0 mg/kg, i.v.). Twenty
      four hours after CdCl2 administration animals were killed and the degree of liver
      toxicity was assessed using plasma alanine aminotransferase (ALT), as well as
      light microscopy. Cadmium chloride administration produced multifocal
      hepatocellular necrosis and increased plasma ALT activity. Pretreatment with
      GdCl3 significantly reduced both the morphological changes and hepatic ALT
      release caused by CdCl2. However, the protection was specific to the liver, and
      did not alter CdCl2 induced testicular injury, as determined by histopathological
      damage. In many cases, the inducible cadmium-binding protein, metallothionein
      (MT) is often an essential aspect of the acquisition of cadmium tolerance in the
      liver. Although cadmium caused a dramatic induction of hepatic MT (32-fold),
      GdCl3 caused only a minor increase (2-fold). Combined CdCl2 and GdCl3 treatment
      did not induce levels to an extent greater than CdCl2 alone. As expected, GdCl3
      also caused a slight increase in the amount of cadmium associated with the liver.
      In cultured hepatocytes isolated from GdCl3 pretreated rats, CdCl2 induced
      cytotoxicity was not significantly altered compared to control hepatocytes,
      indicating that the mechanism of tolerance required the presence of other cell
      types. Thus, GdCl3 attenuation of CdCl2 induced hepatotoxicity does not appear to
      be caused by increased tissue MT content or a decreased susceptibility of
      hepatocytes to cadmium. From these data, we concluded that tolerance to cadmium
      induced hepatotoxicity involves the inhibition of Kupffer cell function which
      results in a decreased inflammatory response and an altered progression of
      hepatic injury. These data further indicate that Kupffer cell function is
      critical to cadmium induced hepatocellular necrosis.

PMID- 9230449
TI  - Graphical information retrieval by browsing meta-information.
AB  - This paper discusses an approach to alleviate the problem in information
      retrieval of finding the right information. This problem arises in traditional
      query-based systems when users do not have enough knowledge about the domain or
      if they do not have an articulate information need. We address this problem by
      combining information about the documents and about the domain of the documents.
      This meta-information can then be browsed by the users with a graphical browser.
      Several navigation aids help the user to find his way. The system contains a
      representation of the medical domain and records from the Medline literature
      database. The paper discusses the representation of the meta-information, the
      browser and the evaluation of the system.

PMID- 9230448
TI  - Diesel exhaust particles and carbon black have adjuvant activity on the local
      lymph node response and systemic IgE production to ovalbumin.
AB  - The possible adjuvant effect of diesel exhaust particles (DEP) on the response to
      the model allergen ovalbumin (OA) was studied in BALB/c mice using the popliteal
      lymph node (PLN) assay. In addition to changes in PLN weight, cell numbers and
      cell proliferation, specific serum IgE anti-OA antibody levels were measured. OA
      inoculated together with DEP into one hind footpad gave a significantly augmented
      response (increase in weight, cell numbers and cell proliferation) in the
      draining popliteal lymph node as compared to DEP or OA alone. Also, the local
      lymph node response was of longer duration when DEP were given with the allergen.
      Experiments in thymus-deficient nu/nu mice indicated that the lymph node response
      observed in BALB/c mice was of a specific immunologic character and not an
      unspecific inflammatory reaction. The OA-specific IgE response was increased in
      mice receiving OA together with DEP as compared to the response in mice receiving
      OA without DEP. Carbon black (CB) was given with and without OA in some
      experiments, as a surrogate for the non-extractable core of DEP. CB was found to
      resemble DEP in its capacity to increase the local lymph node response and serum
      specific IgE response to OA, but CB appeared to be slightly less potent than DEP.
      Thus, both DEP and CB had a significant adjuvant effect on the local immune
      mediated inflammatory response and on the systemic specific IgE response to
      allergen. The results indicate that the non-extractable particle core contributes
      substantially to the adjuvant activity of DEP.

PMID- 9230450
TI  - A SAS macro for constructing simultaneous confidence intervals for multinomial
      proportions.
AB  - Quesenberry and Hurst (1964), Goodman (1965) and Fitzpatrick and Scott (1987)
      proposed simultaneous construction of confidence intervals for multinomial
      proportions, however. statistical computing packages do not generally give one
      the option of specifying the type of construction to be used. We have written a
      SAS macro using PROC IML that takes multinomial cell counts as input and returns
      simultaneous confidence intervals with the user-specified coverage probability.
      Two main features of the macro are its ease of use and its flexibility in
      allowing the user to choose among six methods of constructing confidence
      intervals for multinomial proportions. Based on simulation May and Johnson (1997)
      recommended the intervals proposed by Goodman (1965) in most practical
      applications.

PMID- 9230451
TI  - SWEEPS: a program for the acquisition and analysis of neurophysiological data.
AB  - I describe SWEEPS, a program for the acquisition and analysis of
      neurophysiological data written with LabWindows/CVI. SWEEPS includes many
      features of general interest to neurobiologists, such as digital filtering,
      window discrimination, and the construction of peristimulus time histograms. As
      the program is written using LabWindows/CVI, a C-programming system which
      includes routines for many data-processing and display tasks, it can be easily
      modified to accommodate new analysis needs as they arise.

PMID- 9230452
TI  - QC Validator 2.0: a computer program for automatic selection of statistical QC
      procedures for applications in healthcare laboratories.
AB  - A computer program has been developed to help healthcare laboratories select
      statistical control rules and numbers of control measurements that will assure
      the quality required by clinical decision interval criteria or analytical total
      error criteria. The program (QC Validator 2.0 (QC Validator and OPSpecs are
      registered trademarks of Westgard Quality Corporation, which has applied for a
      patent for this automatic QC selection process. Windows is a registered trademark
      of Microsoft Corporation)) runs on IBM compatible personal computers operating
      under Windows. The user enters information about the method imprecision,
      inaccuracy, and expected frequency of errors, defines the quality required in
      terms of a medically important change (clinical decision interval) or an
      analytical allowable total error, then initiates automatic selection by
      indicating the number of control materials that are to be analyzed (1, 2, or 3).
      The program returns with a chart of operating specifications (OPSpecs chart) that
      displays the selected control rules and numbers of control measurements. The
      automatic QC selection process is based on user editable criteria for the types
      of control rules that can be implemented by the laboratory, total numbers of
      control measurements that are practical, maximum levels of false rejections that
      can be tolerated and minimum levels of error detection that are acceptable for
      detection of medically important systematic or random errors.

PMID- 9230453
TI  - EasyMA: a program for the meta-analysis of clinical trials.
AB  - Meta-analysis of clinical trial data is an increasingly important method in
      clinical research, particularly in the field of therapeutic evaluation. This
      method uses some specific statistical techniques which are not all available on
      standard packages and therefore require specific developments. This paper
      describes a program designed to help medical researchers perform meta-analyses of
      clinical trial data with dichotomous outcomes. This program includes the various
      statistical methods of meta-analysis and enables cumulative meta-analysis and sub
      groups to be performed. A robustness index can be determined and the results
      obtained in table and graphic formats. Data-editing and data-manipulating
      facilities are also possible. Much care has been taken to make the user interface
      as user-friendly as possible, so that the program is within the reach of all
      medical researchers.

PMID- 9230454
TI  - A computer program for constructing multivariate reference models.
AB  - From a statistical point of view the simultaneous interpretation of multiple
      variables should be performed with a multivariate reference model rather than
      with multiple univariate reference intervals. A computer program for constructing
      and testing multivariate reference models is described. The use of the computer
      program is illustrated with a data set of total serum calcium concentrations and
      serum albumin concentrations from 222 2nd year medical students. Using a single
      univariate reference interval for total serum calcium, 17 students were
      classified as having an abnormal calcemic status while using a bivariate
      reference model for total serum calcium and serum albumin, 13 of these 17
      students had in fact normal total serum calcium concentrations, taking into
      account their serum albumin concentrations.

PMID- 9230455
TI  - A computer model and program for xenobiotic disposition during pregnancy.
AB  - A physiologically based pharmacokinetic computer model and program have been
      developed that depict internal disposition of chemicals during pregnancy in the
      mother and embryo/fetus. The model is based on human physiology but has been
      extended to simulate laboratory animal data. The model represents the
      distribution, metabolism, and elimination of two chemicals in both the maternal
      and embryo/fetal systems; the program handles the two chemicals completely
      independently or interactively with the two chemicals sharing routes of
      metabolism and/or elimination. The FORTRAN program computes the concentration of
      the two chemicals in 26 organs/tissues in the pregnant mother and 15
      organs/tissues in the embryo/fetus using a 486DX4 or Pentium PC. Adjustments for
      embryo/fetal organ and tissue volumes as a function of developmental age are made
      utilizing the Gompertz growth equation for the developing embryo/fetus and
      allometric relationships for the developing organs. Various changes in the
      maternal compartments which could affect the distribution of a xenobiotic during
      pregnancy are also included in the model. Input files require estimates of
      binding coefficients, first- and/or second-order metabolism constants, level of
      interaction between the two chemicals, and dosing information. Different possible
      routes of administration are included (e.g., i.v., infusion, oral, dermal, and
      inhalation, as well as repeated doses or exposures). Regression analysis can be
      conducted on any combination of these various parameters to fit actual data.
      Output concentration-time curves are available simultaneously from all 82
      differential equations. An illustrative example compares observed data with
      simulations for imipramine and its demethylated metabolite, desipramine, in both
      the maternal rat and her fetuses. Methyl mercury data for the non-pregnant and
      pregnant rat also are compared with human data. Based on parameters determined
      from analysis of rat data, the model is readjusted for human physiology and
      predicts human maternal and fetal tissue concentrations as a function of time.

PMID- 9230456
TI  - Nonconventional protease catalysis in frozen aqueous solutions.
AB  - During the past decade proteases have been widely used as catalysts in peptide
      synthesis. Unfortunately, they are not ideal ligases. Enzymatic peptide synthesis
      in frozen aqueous systems has been developed as an approach towards the
      suppression of competitive reactions. This paper summarizes reports concerning
      the behaviour of non-enzymatic as well as of enzyme-catalysed reactions when the
      reaction mixture is frozen. The advantages of freezing the reaction mixture in
      serine and cysteine protease-catalysed peptide synthesis, the influence of
      modified reaction conditions and the possible reasons for the yield-increasing
      effect of freezing are discussed.

PMID- 9230457
TI  - Delta-selective opioid peptides containing a single aromatic residue in the
      message domain: an NMR conformational analysis.
AB  - The sequence of deltorphin I, a delta-selective opioid agonist, has been
      systematically modified by inserting conformationally constrained C alpha, alpha
      disubstituted apolar residues in the third position. As expected, substitution of
      Phe with Ac6c, Ac5c and Ac3c yields analogues with decreasing but sizeable
      affinity. Surprisingly, substitution with Aib yields an analogue with almost the
      same binding affinity of the parent compound but with a greatly increased
      selectivity. This is the first case of a potent and very selective opioid peptide
      containing a single aromatic residue in the message domain, that is, only Tyr1.
      Here we report a detailed conformational analysis of [Aib3]deltorphin I and
      [Ac6c3]deltorphin I in DMSO at room temperature and in a DMSO/water cryomixture
      at low temperature, based on NMR spectroscopy and energy calculations. The
      peptides are highly structured in both solvents, as indicated by the exceptional
      finding of a nearly zero temperature coefficient of Val5 NH resonance. NMR data
      cannot be explained on the basis of a single structure but it was possible to
      interpret all NMR data on the basis of a few structural families. The
      conformational averaging was analysed by means of an original computer program
      that yields qualitative and quantitative composition of the mixture. Comparison
      of the preferred solution conformation with two rigid delta-selective agonists
      shows that the shapes of [Aib3]deltorphin I and [Ac6c3]deltorphin I are
      consistent with those of rigid agonists and that the message domain of opioid
      peptides can be defined only in conformational terms.

PMID- 9230458
TI  - Solid-phase synthesis of omega-agatoxin IVA, a P-type calcium channel blocker.
AB  - omega-Agatoxin IVA, isolated from the venom of funnel web spider Agelenopsis
      aperta, blocks potently and selectively P-type calcium channels. This toxin,
      composed of 48 amino acids and containing 8 cysteine residues, was synthesized by
      the solid-phase procedure. The Cys residues were protected by acetamidomethyl
      (Acm) groups which were removed by mercuric acetate. During treatment with
      mercuric acetate, a by-product was detected, involving modification of tryptophan
      residues by the Acm groups. This side reaction can be completely prevented by
      addition of an excess of tryptophan in the reaction medium during Acm
      deprotection. The resulting peptide was submitted to an oxidative refolding, in
      different conditions, in order to determine the most favourable protocol. After
      formation of the four disulphide bonds, the toxin was purified by successive
      preparative HPLC, on two different supports, and fully characterized by
      analytical HPLC, capillary electrophoresis, amino acid analysis, mass
      spectrometry and Edman degradation. It was found to block the P-type calcium
      channel with a similar biological potency as described for the natural product.

PMID- 9230459
TI  - The immunomodulatory activity of peptides related to the DNA contacting loop of
      p53 protein.
AB  - Taking into account the sequence homology existing between thymopoietin II and
      the DNA-binding domain of p53 protein, a series of octapeptides was synthesized,
      related to the wild p53 type protein as well as to its mutated forms, appearing
      in some human tumours. The wild type octapeptide has immunostimulative activity
      with regard to the humoral immune response, but is inactive in the cellular
      immune response. The mutated peptides of p53 differ in their immunomodulatory
      activity from the wild type octapeptide. The Ser5 analogue of the wild peptide is
      a strong stimulant of the humoral immune response and enhances TNF-alpha
      production, while at the same time suppressing the cellular immune response. The
      data suggest that the mutations of p53, which favour tumour development and
      growth, may also change the immune activity of respective p53 fragments.

PMID- 9230460
TI  - An exploration of the effects of constraints on the phosphorylation of synthetic
      protein tyrosine kinase peptide substrates.
AB  - We synthesized by classical solution methods three conformational constrained
      analogues of EDNEYTA, a heptapeptide sequence that represents the common major
      autophosphorylation site of the protein tyrosine kinases (PTKs) of the Src
      family. The correlation between the different structural properties induced by
      the modifications of the native sequence and the propensity of the peptides to
      act as PTK substrates was examined. The kinetic data obtained indicate that the
      introduction of the tyrosine-analogue constraints Tic(OH) and MeTyr, which block
      the ring flexibility, completely prevents the phosphorylation catalysed by the
      kinases Lyn and Fgr. On the other hand PTKIIB/p38syk can phosphorylate the two
      derivatives albeit with an efficiency lower than that found with the native
      sequence. A third derivative contained side chain to side chain cyclization. This
      analogue, in which the freedom of the phenolic moiety is not altered, can be
      phosphorylated by all the PTKs tested with kinetic constants comparable to the
      parent peptide.

PMID- 9230462
TI  - Solution conformation of [D-Pen2, D-Pen5] enkephalin in water: a NMR and
      molecular dynamics study.
AB  - The solution conformation of [D-Pen2, D-Pen5] enkephalin (DPDPE), a highly potent
      delta-selective opioid agonist, was examined by means of NMR, molecular mechanics
      and molecular dynamics methods. The structural information in the solvent water
      was obtained employing one- and two-dimensional methods of 1H and 13C-NMR
      spectroscopy. Based on the distance geometry technique using the ROE data as
      input, 400 conformers were obtained and considered in the structure analysis.
      Alternatively, about 2000 conformers were stochastically generated and related to
      the NMR data after energy minimization. The structure analysis provides one
      conformer in agreement with all NMR data, which belongs to the lowest energy
      conformation group. This structure may serve as a reference conformer for DPDPE
      analogues synthesized with the aim of activity increase.

PMID- 9230461
TI  - Preparation of site-specific isotopically labelled zervamicins, the antibiotic
      peptaibols produced by Emericellopsis salmosynnemata.
AB  - A simple procedure for the preparation of the specifically labelled peptide
      antibiotic zervamicins IC, IIA and IIB has been developed. The zervamicin
      molecules are labelled with stable isotopes by culturing the Emericellopsis
      salmosynnemata on a well-defined synthetic medium containing the highly
      isotopically enriched amino acid. To obtain the peptide with the specifically and
      highly enriched amino acid residue, precautions have been taken to prevent any de
      novo biosynthesis of the particular amino acid from unlabelled precursors. The
      enrichment of the labelled peptide is determined by mass spectrometric analysis.
      Following this method we have incorporated [2',4',5',6',7'-2H5]-L-Trp-1, [1'-15N]
      L-Trp-1 and [2',3',4',5',6'-2H5]-L-Phl-16 into zervamicins IC, IIA and IIB on the
      preparative scale and without scrambling of the label. Thus, using the procedures
      described, isotopically labelled zervamicins can be prepared, allowing them to be
      studied by solid-state NMR.

PMID- 9230463
TI  - Design of peptides using alpha, beta-dehydro-residues: synthesis, crystal
      structure and molecular conformation of N-Boc-L-Val-delta Phe-delta Phe-L-Ala
      OCH3.
AB  - To obtain general rules of peptide design using alpha, beta-dehydro-residues, a
      sequence with two consecutive delta Phe-residues, Boc-L-Val-delta Phe-delta Phe-L
      Ala-OCH3, was synthesized by azlactone method in solution phase. The peptide was
      crystallized form its solution in an acetone/water mixture (70:30) in space group
      P6(1) with a = b = 14.912(3) A, c = 25.548(5) A, V = 4912.0(6) A3. The structure
      was determined by direct methods and refined by a full matrix least-squares
      procedure to an R value of 0.079 for 2891 observed [I > or = 3 delta (1)]
      reflections. The backbone torsion angles phi 1 = 54(1) degrees, psi 1 = 129(1)
      degrees, omega 1 = -177(1) degrees, phi 2 = 57(1) degrees, psi 2 = 15(1) degrees,
      omega 2 = -170(1) degrees, phi 3 = 80(1) degrees, psi 3 = 7(2) degrees, omega 3 =
      -177(1) degrees, phi 4 = -108(1) degrees and psi T4 = -34(1) degrees suggest that
      the peptide adopts a folded conformation with two overlapping beta-turns of types
      II and III'. These turns are stabilized by two intramolecular hydrogen bonds
      between the CO of the Boc group and the NH of delta Phe3 and the CO of Val1 and
      the NH of Ala4. The torsion angles of delta Phe2 and delta Phe3 side chains are
      similar and indicate that the two delta Phe residues are essentially planar. The
      folded molecules from head-to-tail intermolecular hydrogen bonds giving rise to
      continuous helical columns which run parallel to the c-axis. This structure
      established the formation of two beta-turns of types II and III' respectively for
      sequences containing two consecutive delta Phe residues at (i + 2) and (i + 3)
      positions with a branched beta-carbon residue at one end of the tetrapeptide.

PMID- 9230464
TI  - Towards the understanding of the folding of methylene units in the glutamine
      residue.
AB  - The conformational preferences of the methylenic sequence in the side chain of
      the glutamine residue were investigated by ab initio and semi-empirical quantum
      mechanical calculations and examination of both the Brookhaven Protein Databank
      and Cambridge Structural Data Base. The results were analysed on the basis of our
      previous findings about the folding of methylene groups in aliphatic segments.
      Both energy calculations and the crystallographic structure of small peptides
      indicate that methylene units of the glutamine residue tend to fold in a gauche
      conformation. In contrast, such groups usually adopt an all-trans conformation in
      proteins due basically to the entropic and solvent contributions. These results
      have been demonstrated by computing the entropic correction to the free energy
      and evaluating the solvent effects through SCRF calculations.

PMID- 9230465
TI  - The use of crown ethers in peptide chemistry-V. Solid-phase synthesis of peptides
      by the fragment condensation approach using crown ethers as non-covalent
      protecting groups.
AB  - We have previously described the conditions by which peptide synthesis by the
      solid-phase fragment condensation approach can be carried out using crown ethers
      as non-covalent protection for the N alpha-amino group. Here we demonstrate that
      the procedure can be extended to large, partially protected peptide fragments
      possessing free Lys and/or Arg residues. The first step was to ensure that
      complex formation on the side chain of amino acids was not detrimental to the
      methodology and exhibited the same solubility and coupling properties as N alpha
      complexed peptides. Thus, a model hexapeptide was synthesized using Fmoc
      chemistry containing Lys and Arg residues, which, when complexed with 18-Crown-6,
      was readily soluble in DCM and coupled quantitatively to a resin-bound
      tetrapeptide. Two tripeptides were then prepared, one containing a free Ser
      residue, the other free Tyr, to examine the possible occurrence of side
      reactions. After coupling using standard conditions only the former tripeptide
      exhibited the formation of the O-acylation by-product (5%). Another model
      hexapeptide containing Lys, Tyr, Ser and Asp protected with a TFA-stable
      adamantyl group was complexed with 18-Crown-6 and coupled to the resin-bound
      tetrapeptide with near quantitative yield. Extending the length of the peptide to
      21 and 40 residues, which represent sequences Gly52 to Leu72 (21-mer) and Pro33
      to Leu72 (40-mer) from Rattus norvegicus chaperonin 10 protein, respectively,
      resulted in partially protected fragments that were readily soluble in water,
      thus enabling purification by RP-HPLC. Complexation with 18-Crown-6 gave two
      highly soluble products that coupled to resin-board tetramer with 68% and 50%
      coupling efficiencies for the 21-mer and 40-mer, respectively. Treatment with 1%
      DIEA solutions followed by acidolytic cleavage and purification of the major
      product confirmed that the correct product has been formed, when analysed by
      amino acid analysis and ESI-MS. These results served to extend the methodology of
      non-covalent protection of large partially protected peptide fragments for the
      stepwise fragment condensation of polypeptides.

PMID- 9230466
TI  - Folded structures in protonated reduced dipeptides.
AB  - Reduced dipeptides with the general formula RCO-Xaa-rXbb-N+HR'R" (rXbb, reduced
      analogue of residue Xbb: NH-C alpha HR1-CrH2) are shown to adopt a folded
      conformation in solution and in the solid state. The protonated reduced amide
      bond is an active proton donor capable of interacting with a peptide carbonyl to
      give a strong hydrogen bond topologically equivalent to the i+2 or i+3-->i
      interaction. The resulting conformation is similar to the y- or beta-turn
      structure found in peptides and proteins.

PMID- 9230467
TI  - On the mechanism of hormone recognition and binding by the CCK-B/gastrin
      receptor.
AB  - Lipidation with long-chain di-fattyacyl-glycerol moieties was used to anchor
      gastrin in CCK peptides irreversibly to lipid bilayers lipopeptide transfer to
      model phospholipid bilayers is fast and quantitative, leading to a different mode
      of insertion of lipo-gastrin and lipo-CCK in lipid layers. Lipo-gastrin remains
      exposed to the bulk solvent in a predominantly random coil structure as a
      consequence of electrostatic repulsion, whereas lipo-CCK exhibits a pronounced
      tendency to form peptide domains with insertion of its C-terminus into more
      hydrophobic compartments of the bilayers. Thereby Ca2+ at physiological
      concentrations favours this aggregational phenomenon. Since both lipo-peptides
      were found to retain almost full receptor affinity despite their irreversible
      anchorage to the bilayer, a membrane-bound pathway in the receptor recognition
      and binding process is indeed possible. According to the data collected in this
      study, CCK might possibly use this pathway, whereas accumulation of gastrin on
      the cell membrane with prefolding of the ligand at the water/lipid interface is
      hardly conceivable. Nevertheless the observed receptor interaction of the
      deliberately membrane-anchored gastrin offers interesting constraints for
      computational docking experiments on a modelled CCK-B/gastrin receptor by
      additionally taking into account information derived from mutagenesis studies.
      Despite the limitations of such modelling experiments, the resulting picture of
      the gastrin/receptor complex allowed the visualization and rationalization of the
      experimental results of the extensive structure-function studies performed
      previously on this family of gastrointestinal hormones.

PMID- 9230468
TI  - Synthesis, characterization and conformational analysis of gp 120-derived
      synthetic peptides that specifically enhance HIV-1 infectivity.
AB  - A series of peptides patterned on the principal neutralizing domain of the HIV-1
      envelope glycoprotein gp 120 have been synthesized by solid-phase techniques.
      Interestingly, in vitro experiments have shown that some of these peptides
      specifically interact with CD4 and, in particular, that the peptide corresponding
      to the sequence 307-330 of the HIV-1 MN isolate was able to enhance infection in
      a dose-specific and not a strain-restricted way. To bypass problems observed in
      preliminary runs, peptides were synthesized by both Fmoc and Boc chemistry.
      Comparison of the two strategies has allowed the set up of convenient protocols
      for the preparation of the target peptides in good yield, and with the high
      purity grade needed for biological and physiochemical studies. Since the
      biological effects were present in the carboxyl-free C-terminal linear peptide
      but not in the amidated C-terminal analogue, preliminary conformational studies
      by circular dichroism and nuclear magnetic resonance techniques were also
      performed in an attempt to correlate these effects with possible contributions of
      structured conformations as predicted by theoretical calculations. The
      possibility of a beta-turn structure for the crucial Gly-Pro-Gly-Arg sequence has
      been confirmed by 2D NMR experiments. Ongoing studies suggest the exploitation of
      the activating properties of the MN-derived peptides to design a more sensitive
      and innovative serological test based on the virus itself and not on anti-HIV
      antibodies, as is the case for the large majority of tests currently in use.

PMID- 9230470
TI  - Improved detection of human antibodies to a Plasmodium antigen using a peptide
      modified with Aib residues.
AB  - A 17-mer sequence was selected as a model to study the influence of modifications
      of terminal ends both on the conformational of a peptide and on its antigenicity
      towards naturally developing antibodies. This sequence corresponded to a tandemly
      repeated motif, found in a long repetitive region, with high helical propensity,
      of a Plasmodium falciparum liver-stage antigen (LSA-1), immunogenic in man. Our
      model peptide was synthesized with ionizable or non-ionizable ends, or modified
      in both extremities by introduction of the helix-promoting residue alpha
      aminoisobutyric acid (Aib). Helical contribution, absent in the 17 amino-acid
      sequence possessing ionizable ends, was detectable when non-ionizable ends were
      introduced, and dramatically increased in the Aib-modified analogue. The presence
      of ionizable ends totally abolished reactivity towards human sera, otherwise
      detectable with the peptide possessing non-ionizable ends. While modification by
      Aib residues was neither detrimental nor beneficial to antigenicity in solution,
      it clearly resulted in an improved sensitivity of the specific antibody detection
      when used as solid-phase antigen in ELISA.

PMID- 9230469
TI  - Position three in vasopressin antagonist tolerates conformationally restricted
      and aromatic amino acid substitutions: a striking contrast with vasopressin
      agonists.
AB  - We report the solid-phase synthesis and some pharmacological properties of 12
      position three modified analogues (peptides 1-12) of the potent non-selective
      antagonist of the antidiuretic (V2-receptor), vasopressor (V1a-receptor)
      responses to arginine vasopressin (AVP) and of the uterine contracting (OT
      receptor) responses to oxytocin (OT), [1(-beta mercapto-beta,beta
      pentamethylenepropionic acid)-2-O-ethyl-D-tyrosine 4-valine] arginine vasopressin
      [d(CH2)5D-Tyr(Et)2VAVP] (A) and two analogues of (B) (peptides 13,14), the
      1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid3 (Tic3) analogue of (A).
      Peptides 1-12 have the following substituents at position three in (A): (1) Pro;
      (2) Oic; (3) Atc; (4) D-Atc; (6) D-Phe; (7) Ile; (8) Leu; (9) Tyr; (10) Trp; (11)
      Hphe; (12) [HO]Tic; Peptide (13) is the Tyr-NH2(9) analogue of (B): Peptide (14)
      is the D-Cys(6) analogue of (B). All 14 new peptides were evaluated for agonistic
      and antagonistic activities in in vivo V2 and V1a assays and in vitro (no Mg2+)n
      oxytocic assays. With the exception of the D-Phe3 peptide (No. 6), which exhibits
      very weak V2 agonism (approximately 0.0017 U/mg), none of the remaining 13
      peptides exhibit any agonistic activities in these assays. In striking contrast
      to their deleterious effects on agonistic activities in AVP, the Pro3, Oic3, Tyr3
      and Hphe3 substitutions in (A) are very well tolerated, leading to excellent
      retention of V2, V1a and OT antagonistic potencies. All are more potent as V2
      antagonists than the Ile3 and Leu3 analogues of (A). The Tyr-NH2(9) and D-Cys(6)
      substitutions in (B) are also well tolerated. The anti-V2 pA2 values of peptides
      1-5 and 7-14 are as follows (1) 7.77 +/- 0.03; (2) 7.41 +/- 0.05; (3) 6.86 +/-
      0.02; (4) 5.66 +/- 0.09; (5) approximately 5.2; (7) 7.25 +/- 0.08; (8) 6.82 +/-
      0.06; (9) 7.58 +/- 0.05; (10) 7.61 +/- 0.08; (11) 7.59 +/- 0.07; (12) 7.20 +/-
      0.05; (13) 7.57 +/- 0.1; (14) 7.52 +/- 0.06. All analogues antagonize the
      vasopressor responses to AVP, with anti-V1a pA2 values ranging from 5.62 to 7.64,
      and the in vitro responses to OT, with anti-OT pA2 values ranging from 5.79 to
      7.94. With an anti-V2 potency of 7.77 +/- 0.03, the Pro3 analogue of (A) is
      surprisingly equipotent with (A), (anti-V2 pA2 = 7.81 +/- 0.07). These findings
      clearly indicate that position three in AVP V2/V1a antagonists, in contrast to
      position three in AVP agonists, is much more amenable to structural modification
      than had heretofore been anticipated. Furthermore, the surprising retention of V2
      antagonism exhibited by the Pro3, Oic3, Tyr3, Trp3 and Hphe3 analogues of (A),
      together with the excellent retention of V2 antagonism by the Tyr-NH2(9) and D
      Cys6 analogues of (B) are promising new leads to the design of potent and
      possibly orally active V2 antagonists for use as pharmacological tools and/or as
      radioiodinatable ligands and for development as potential therapeutic agents for
      the treatment of the hyponatremia caused by the syndrome of the inappropriate
      secretion of the antidiuretic hormone (SIADH).

PMID- 9230471
TI  - Purification, sequence determination and synthesis of seminal plasma peptides and
      synthesis of some of their analogues.
AB  - Three peptides were isolated from bovine seminal plasma and purified to
      homogeneity. The amino acid sequences, as determined by FAB mass spectrometry,
      are the following: pGlu-Ala-Glu-Ser-Asn-OH, pGlu-Ala-Glu-Ser(PO3H2-Asn-OH and
      pGlu-Val-Gly-Glu-Ser-Glu-Asn-OH. These three peptides and some of their analogues
      were synthesized using liquid- and solid-phase techniques. The pentapeptide pGlu
      Ala-Glu- Ser-Asn-OH showed a remarkable affinity for kinase NII and a strong
      inhibiting activity in DNA transcription. These findings support the hypothesis
      that phosphorylated acidic domains of nuclear non-histone proteins could bind to
      DNA, thereby controlling transcription.

PMID- 9230472
TI  - Lipid-induced secondary structures and orientations of (Leu5)-enkephalin: helical
      and crystallographic double-bend conformers revealed by IRATR and molecular
      modelling.
AB  - Lipid-induced secondary structures and orientations of the two enantiomeric
      [Leu5]-enkephalins, L-Tyr-Gly-Gly-L-Phe-L-Leu, and D-Tyr-Gly-Gly-D-Phe-D-Leu, on
      flat multi-bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      were examined with polarized attenuated total reflection IR (IRATR) spectroscopy
      and molecular mechanics procedures. The membrane-bound peptides showed identical
      IR spectra in the amide I and II band regions that indicated membrane-induced
      secondary structures and specific orientations of the non-zwitterionic molecules.
      A Lorentzian band shape analysis based on second derivatives of the original
      curves and observed band polarizations suggested the presence of helical
      structures (beta III- and alpha-turns), oriented more or less perpendicular to
      the membrane surface. Other folded structures, e.g. beta I- and gamma turns, were
      not excluded. Molecular modelling of non-zwitterionic (Leu5)-enkephalin with two
      beta III-turns or an alpha-turn resulted in essentially four low-energy
      conformers containing (i) two beta III-turns, (ii) one alpha-turn, (iii) a beta
      III-turn fused to an alpha-turn, and (iv) a beta III-turn fused to a beta I-turn
      as in the crystallographic molecular conformation described by Aubry et al.
      [Biopolymers 28, 27-40 (1989)]. Zwitterionic [Leu5]-enkephalin with two beta III
      turns collapsed to a C13 turn (a distorted alpha-turn) bridged by a gamma I-turn
      (v). The alignment of the amide I oscillators within the helical structures, (i),
      (ii) and (iii), and the double-bend structures, (iv) and (v), explained the
      observed amide I and II polarizations. Differences between these and other lipid
      induced [Leu5]-enkephalin conformers reported in the literature may be caused by
      the lipid polymorphism of the model membranes used. Possible implications of the
      new conformers for the molecular mechanism of opioid receptor selection are
      discussed in terms of the membrane compartments theory.

PMID- 9230473
TI  - Computational study of the conformational domains of peptide T.
AB  - The conformational preferences of peptide T (ASTTTNYT) were analysed by means of
      computational methods. A thorough exploration of the conformational space was
      carried out within the framework of the molecular mechanics approach, using
      simulated annealing as a searching strategy. Specifically, in order to obtain a
      subset of low-energy conformations with energies close to the global minimum as
      complete as possible, a simulated annealing protocol was repeated several times
      in a recursive fashion. The results of the search indicate that the peptide
      exhibits a alpha-helical character although most of the conformations
      characterized, including the global minimum, can be described as bent
      conformations. Conformations exhibiting beta-turn motives previously proposed
      from NMR studies were also characterized, although they are not very predominant
      in the set of low-energy conformations.

PMID- 9230474
TI  - Enzymatic peptide synthesis in frozen aqueous solution: use of N alpha
      unprotected peptide esters as acyl donors.
AB  - The ability of the endopeptidase alpha-chymotrypsin (EC 3.4.21.1) to catalyse the
      reaction of various N alpha-unprotected di- and tripeptide ester derivatives with
      H-Leu-NH2, and with a series of C-terminal free di- and tripeptides at -15
      degrees C in frozen aqueous solution was investigated. The enzyme is able to
      synthesize N- and C-terminal unprotected penta- and hexapeptides in up to 92%
      yield, depending on the amino component used, in a single-step segment
      condensation reaction. Freezing the reaction mixture resulted in significantly
      increased peptide yields compared with the reaction at room temperature. The
      enzyme shows a modified nucleophilic specificity in frozen solution compared with
      room temperature. Nucleophilic amino components with positively charged amino
      acids in P2'-position are accepted.

PMID- 9230475
TI  - Neoglycopeptide synthesis and purification in multi-gram scale: preparation of O
      (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-N alpha-fluoren-9-yl
      methoxycarbonyl-hydroxyproline and its use in the pilot-scale synthesis of the
      potent analgesic glycopeptide O1.5-beta-D-galactopyranosyl [DMet2,
      Hyp5]enkephalinamide.
AB  - The preparation of a beta-galactosylated hydroxyproline derivative and its use in
      the multi-gram solid-phase synthesis of the potent analgesic neoglycopeptide O1.5
      beta-D-galactopyranosyl [D-Met2, Hyp5]enkephalinamide is described in this paper.
      The most closely related impurities have been identified, isolated and
      characterized. Significant aspects of the synthesis and purification affecting
      yields and purity of both the building block and the target neoglycopeptide are
      discussed.

PMID- 9230476
TI  - Conformational characterization of the 1-aminocyclobutane-1-carboxylic acid
      residue in model peptides.
AB  - A series of N- and C-protected, monodispersed homo-oligopeptides (to the
      dodecamer level) from the small-ring alicyclic C alpha, alpha-dialkylated glycine
      1-aminocyclobutane-1-carboxylic acid (Ac4c) and two Ala/Ac4c tripeptides were
      synthesized by solution methods and fully characterized. The conformational
      preferences of all the model peptides were determined in deuterochloroform
      solution by FT-IR absorption and 1H-NMR. The molecular structures of the amino
      acid derivatives Z-Ac4c-OH and Z2-Ac4c-OH, the tripeptides Z-(Ac4c)3-OtBu, Z-Ac4c
      (L-Ala)2-OMe and Z-L-Ala-Ac4c-L-Ala-OMe, and the tetrapeptide Z-(Ac4c)4-OtBu were
      determined in the crystal state by X-ray diffraction. The average geometry of the
      cyclobutyl moiety of the Ac4c residue was assessed and the tau(N-C alpha-C') bond
      angle was found to be significantly expanded from the regular tetrahedral value.
      The conformational data are strongly in favour of the conclusion that the Ac4c
      residue is an effective beta-turn and helix former. A comparison with the
      structural propensities of alpha-aminoisobutyric acid, the prototype of C alpha,
      alpha-dialkylated glycines, and the other extensively investigated members of the
      family of 1-aminocycloalkane-1-carboxylic acids (Acnc, with n = 3, 5-8) is made
      and the implications for the use of the Ac4c residue in conformationally
      constrained peptide analogues are briefly examined.

PMID- 9230477
TI  - Synthesis and screening of an indexed motif-library containing non-proteinogenic
      amino acids.
AB  - In an effort to increase the probability of finding novel peptides in resin-bound
      combinatorial libraries displaying affinity to various macromolecular targets, we
      increased the diversity of a solid-phase library considerably by synthesizing
      multiple structures on each bead - a motif-library - including 45 building
      blocks. The building blocks consist of L-aa, D-aa and eight hydrophobic non
      proteinogenic alpha-amino acids. A library with the format O-Z0-1-O-Z0-1-O-XX
      resin was synthesized giving the four motifs OOOXX, OZOOXX, OOZOXX, OZOZOXX
      corresponding to 364.500 different motifs (45(3) x 4 theoretical combinations).
      The positions O are defined amino acids while Z represents three mixtures pi,
      omega, phi, where pi is a mixture of polar and charged residues, omega is a
      mixture of aliphatic residues and phi is a mixture of aromatic residues. X
      represents a mixture of all 45 residues. The library was screened with the
      macromolecular target streptavidin which served as a model receptor. Binding
      peptides were sequenced by microsequencing. We included small amounts of
      norvaline and norleucine in the library, which served as index residues to be
      able to distinguish between LD-amino acids and other residues with the same
      retention time in the HPLC system. Beads that interact with the receptor were
      found, and the binding motifs that appeared had no homology to known binding
      motifs found in either L-aa or D-aa libraries, instead motifs with the non
      proteinogenic residues L-phenylglycine, O-benzyl-L-hydroxyproline and O-benzyl-L
      tyrosine dominated. The novel peptides inhibit binding of biotin to streptavidin
      but do not bind to avidin, and the affinity is higher than the peptides found in
      linear all L-aa peptide libraries.

PMID- 9230478
TI  - Constrained refinement based on NOE and chemical shift information: the monomer
      form of arginine-vasopressin-like insect factor.
AB  - Via the refinement process of the monomer form of an arginine-vasopressin-like
      insect factor, the paper analyses the most relevant NMR information to define the
      solution structure of a flexible peptide. The relative importance of the
      different NOE constraints is discussed.

PMID- 9230479
TI  - Evaluation of carbodiimides using a competition method.
AB  - A competitive reaction of activated Boc-Ala-OH and Boc-Phe-OH with H-Leu-resin
      has been developed for assessing the relative efficiencies of different
      carbodiimides. This allowed a comparison of the efficiency of the carbodiimides
      N,N'-dicyclohexylcarbodiimide,N,N'-diisopropylcarbodiimide, N-tert-butyl-N'
      methylcarbodiimide and N-tert-butyl-N'-ethylcarbodiimide. Comparable results were
      obtained when these reagents were used for the preformation of symmetrical
      anhydrides or of 1-hydroxybenzotriazole esters in situ. Differential
      incorporation was observed when asymmetrical carbodiimides were used for peptide
      bond formation by the direct carbodiimide procedure.

PMID- 9230480
TI  - Lipopeptides with improved properties: structure by NMR, purification by HPLC and
      structure-activity relationships of new isoleucyl-rich surfactins.
AB  - The biosynthesis of bacterial isoleucyl-rich surfactins was controlled by
      supplementation of L-isoleucine to the culture medium. Two new variants, the
      [Ile4,7]- and [Ile2,4,7]surfactins, were thus produced by Bacillus subtilis and
      their separation was achieved by reverse-phase HPLC. Amino acids of the
      heptapeptide moiety were analysed by chemical methods, and the lipid moiety was
      identified by beta-hydroxy anteiso pentadecanoic acid by combined GC/MS.
      Sequences were established on the basis of two-dimensional NMR data. Because
      conformational parameters issuing from NMR spectra suggested that the cyclic
      backbone fold was globally conserved in the new variants, structure-activity
      relationships were discussed in details on the basis of the three-dimensional
      model of surfactin in solution. Indeed, both variants have increased surface
      properties compared with that of surfactin, and this improvement is assigned to
      an increase of the hydrophobicity of the apolar domain favouring micellization.
      Furthermore, the additional Leu-to-Ile substitution at position 2 in the
      [Ile2,4,7]surfactin leads to a substantial increase of its affinity for calcium,
      when compared with that of [Ile4,7]surfactin or surfactin. This effect is
      assigned, from the model, to an increase in the accessibility of the acidic side
      chains constituting the calcium binding site. Thus, the propensities of such
      active lipopeptides for both hydrophobic and electrostatic interactions were
      improved, further substantiating that they can be rationally designed.

PMID- 9230481
TI  - Proteolytically stable peptides by incorporation of alpha-Tfm amino acids.
AB  - A series of model peptides containing alpha-trifluoromethyl-substituted amino
      acids in five different positions relative to the predominant cleavage site of
      the serine protease alpha-chymotrypsin was synthesized by solution methods to
      investigate the influence of alpha-Tfm substitution on the proteolytic stability
      of peptides. Proteolysis studies demonstrated absolute stability of peptides
      substituted to the P1 position and still considerable proteolytic stability for
      peptides substituted at the P2 and P'2 positions compared with the corresponding
      unsubstituted model peptide. Comparison with peptides containing the fluorine
      free disubstituted amino acid alpha-aminoisobutyric acid allowed to separate
      electronic from steric effects. Furthermore, the absolute configuration of the
      alpha-Tfm-substituted amino acid was found to exert considerable effects on the
      proteolytic stability, especially in P'1 substituted peptides. Investigations of
      this phenomenon using empirical force field calculations revealed that in the
      (S,R,S)-diasteromer the steric constraints exhibited by the alpha-Tfm group can
      be outweighed by an advantageous interaction of the flourine atoms with the
      serine side chain of the enzyme. In contrast, a favourable interaction between
      substrate and enzyme is impossible for the (S,S,S)-diastereomer.

PMID- 9230482
TI  - The structural and aggregation properties of the synthetic C-terminal half (104
      mer) polypeptide from HIV p24gag resemble those of full-length protein.
AB  - The aggregation and structural properties of the synthetic C-terminal half
      [Ala330, Ala350(270-373; 104-mer)] polypeptide from HIV-1 p24gag were studied. In
      concentrated solutions the synthetic polypeptide aggregated to tetramers which,
      upon dilution, gave a mixture of monomeric and dimeric and dimeric species. These
      results correlated well with the in vitro aggregation properties of recombinant
      p24. The tetrameric form of the synthetic polypeptide had a pI which differed by
      about four units from that of the mixture of monomeric and dimeric species. CD
      studies indicated that the latter contained, in aqueous solutions, a compact
      molecule lacking, however, a defined tertiary structure. Addition of MeOH to
      aqueous solutions of both tetramer and monomer/dimer mixture induced a more
      defined structure, which was assigned to that of an alpha + beta protein in
      agreement with secondary structure predictions. A model of the dimeric form of
      the 104-mer, which takes into account the results presented here and those from a
      study on the specificity of a set of anti-104-mer MoAbs, is presented. Finally,
      the results indicated that the structure of the 104-mer in its dimeric form is
      similar to that adopted by the same sequence when part of full-length p24.

PMID- 9230483
TI  - New caerin antibacterial peptides from the skin glands of the Australian tree
      frog Litoria xanthomera.
AB  - The secretion of the skin glands of the 'orange-thighed frog' Litoria xanthomera
      contains seven peptides. One of these is the know hypotensive peptide caerulein.
      Two new peptides, caerin 1.6 [GLFSVLGAVAKHVLPHVVPVIAEKL(NH2)], and caerin 1.7
      [GLFKVLGSVAKHLLPHVAPVIAEKL(NH2)] show antibacterial properties. Two other
      peptides lack the first two amino acid residues of caerins 1.6 and 1.7 and show
      no antibacterial activity. The identification of the peptides in Litoria
      xanthomera confirms that this species is related to Litoria caerula, Litoria
      gilleni and Litoria splendida but not as closely as those three species are
      related to each other.

PMID- 9230484
TI  - Solid-phase synthesis of tyrosyl H-phosphonopeptides and methylphosphonopeptides.
AB  - Phosphopeptides are a useful tool for the investigation of phosphorylation as a
      reversible posttranslational modification. There is a growing interest in using
      mimics of phosphoamino acids involved in phosphorylation in order to study the
      enzymes concerned in these processes. These mimics should contain a non
      hydrolysable or isoelectrically modified phosphate moiety to be used as a
      specific inhibitor of phosphatases and kinases. We introduce sold-phase synthesis
      of H- and methylphosphonopeptides as a new class of mimics of phosphotyrosyl
      peptides. The peptides were synthesized on solid phase using the standard
      fluorenyl-methyloxycarbonyl (Fmoc) strategy. Tyrosine residues were incorporated
      as allyl-protected derivatives, which were selectively deprotected on the resin
      by treatment with Pd(PPh3)4. The peptide resin carrying the side-chain
      unprotected tyrosine of the model peptide Gly-Gly-Tyr-Ala was phosphonylated with
      di-tert-butyl-N,N-diethyl-phosphoramidite in the presence of 1H-tetrazole,
      yielding H-phosphonopeptides after trifluoroacetic acid (TFA) cleavage.
      Alternatively, phosphonylation of the unprotected tyrosine with O-tert-butyl-N,N
      diethyl-P-methylphosphonamidite catalysed by 1H-tetrazole and followed by
      oxidation led to the methyphosphonopeptides after TFA cleavage. We obtained both
      the H-phosphonopeptides and the methylphosphonopeptides of the tetrapeptide in
      high yields and purities above 90%, according to reversed-phase high-performance
      liquid chromatography (RP-HPLC). To investigate the general applicability of our
      new methodology, we synthesized phosphonopeptides up to 13 amino acids long,
      corresponding to recognition sequences of tyrosine kinases. After cleavage and
      deprotection, all phosphonopeptides were obtained in high yields and purities of
      about 90%, as shown by mass spectrometry. The only by-product found was the
      unmodified peptide.

PMID- 9230485
TI  - Total synthesis of zervamicin IIB and its deuterium-labelled analogues.
AB  - For the first time the total synthesis of the peptaibol zervamicin IIB is
      described. Synthesis of this peptaibol was achieved by the Fmoc/tert-butyl
      strategy in solution using a fragment condensation approach. Three fragments of
      zervamicin IIB were obtained by stepwise elongation with Fmoc amino acids using
      BOP as a coupling reagent. For the introduction of the highly sterically hindered
      alpha-aminoisobutyric acid residues BOP/DMAP activation was applied. The fmoc
      group was removed by reaction with 0.1 M NaOH in dioxane/methanol/water (30/9/1,
      v/v/v). Peptide fragments were coupled by means of a new coupling reagent, CF3
      PyBOP. Using the strategy developed, zervamicin IIB and two analogues
      specifically deuterium-labelled at different positions of the glutamine-11
      residue have been synthesized in 40% overall yield based on the isotopically
      labelled amino acid and with 98 +/- 2% of isotope enrichment. FAB mass
      spectroscopy, 600 MHz 1H-NMR spectroscopy and high-performance liquid
      chromatography provided convincing evidence that the synthetic products,
      zervamicin IIB and its deuterium-labelled analogues, fully correspond to the
      naturally occurring zervamicin IIB.

PMID- 9230486
TI  - Positional dependence of the effects of negatively charged Glu side chains on the
      stability of two-stranded alpha-helical coiled-coils.
AB  - The effects on protein stability of negatively charged Glu side chains at
      different positions along the length of the alpha-helix were investigated in the
      two-stranded alpha-helical coiled-coil. A native coiled-coil has been designed
      which consists of two identical 35 residue polypeptide chains with a heptad
      repeat QgVaGbAcLdQeKf and a Cys residue at position 2 to allow the formation of
      an interchain 2-2' disulphide bridge. This coiled-coil contains no intra- or
      interchain electrostatic interactions and served as a control for peptides in
      which Glu was substituted for Gln in the e or g heptad positions. The effect of
      the substitutions on stability was determined by urea denaturation at 20 degrees
      C with the degree of unfolding monitored by circular dichroism spectroscopy. A
      Glu substituted for Gln near the N-terminus in each chain of the coiled-coil
      stabilizes the coiled-coil at pH 7, consistent with the charge-helix dipole
      interaction model. This stability increase is modulated by pH change and the
      addition of salt (KCl or guanidine hydrochloride), confirming the electrostatic
      nature of the effect. In contrast, Glu substitution in the middle of the helix
      destabilizes the coiled-coil because of the lower helical propensity and
      hydrophobicity of Glu compared with Gln at pH7. Taking the intrinsic differences
      into account, the apparent charge-helix dipole interaction at the N-terminus is
      approximately 0.35 kcal/mol per Glu substitution. A Glu substitution at the C
      terminus destabilizes the coiled-coil more than in the middle owing to the
      combined effects of intrinsic destabilization and unfavourable charge-helix
      dipole interaction with the negative pole of the helix dipole. The estimated
      destabilizing charge-helix dipole interaction of 0.08 kcal/mol is smaller than
      the stabilizing interaction at the N-terminus. The presence of a 2-2'disulphide
      bridge appears to have little influence on the magnitude of the charge-helix
      dipole interactions at either end of the coiled-coil.

PMID- 9230487
TI  - Large-scale production of peptides using the solid-phase continuous flow method.
      Preparative synthesis of the novel tachykinin antagonist MEN 10627.
AB  - The large-scale solid-phase continuous flow synthesis of the bicyclic peptide MEN
      10627, a new potent Neurokinin A receptor antagonist, is described using the Fmoc
      polyamide method on both macrosorb 125 and Macrosorb 250 resin. A new synthesizer
      designed in-house was realized by assembling Whitey valves and Waters pump in
      order to allow small-scale (0.0001 mol; 1 x 10 cm Omnifit columns) synthetic
      studies which were strongly predictive of the conditions required for large-scale
      (0.01-0.10 mol; 3.6 or 5.9 x 46 cm Buchi columns) production, performed on the
      same apparatus.

PMID- 9230489
TI  - A field trial of the effectiveness of behavioral treatment for sexual
      dysfunctions.
AB  - The present study was a field trial of behavioral sex therapy for 365 married
      couples presenting with a range of sexual dysfunctions. Treatment occurred at an
      outpatient sexual dysfunction clinic of a large medical center using a
      multidisciplinary staff. Findings supported the external validity of behavioral
      sex therapy. The success rate for the total sample (65%) was comparable to that
      of previous investigations, and there were very few dropouts (1.6%) from
      treatment. In addition, outcomes did not vary significantly as a function of
      diagnoses, gender, or a history of sexual abuse. The amount of sensate focus
      completed in the last week of treatment was the strongest predictor of successful
      treatment. For some diagnoses, however, couple comorbidity reduced treatment
      success. Results indicated that behavioral sex therapy is effective in real-world
      clinical settings.

PMID- 9230488
TI  - Conformational analysis of the dipeptide taste ligand L-aspartyl-D-2-aminobutyric
      acid-(S)-alpha-ethylbenzylamide and its analogues by NMR spectroscopy, computer
      simulations and X-ray diffraction studies.
AB  - A dipeptide taste ligand L-aspartyl-D-2-aminobutyric acid-(S)-alpha
      ethylbenzylamide was found to be about 2000 times more potent than sucrose. To
      investigate the molecular basis of its potent sweet taste, we carried out
      conformational analysis of this molecular and several related analogues by NMR
      spectroscopy, computer simulations and X-ray crystallographic studies. The
      results of the studies support our earlier model that an L-shape molecular array
      is essential for eliciting sweet taste. In addition, we have identified an
      aromatic group located between the stem and the base of the L-shape, which is
      responsible for enhancement of sweetness potency. In this study, we also assessed
      the optimal size of the essential hydrophobic group (X) and the effects of the
      chirality of the second residue toward taste.

PMID- 9230490
TI  - Changes in premarital counseling as related to older cohorts of married couples.
AB  - Within a sample of 256 current and former members of the Christian Church
      (Disciples of Christ), it was found that the longer the time since husbands or
      wives had married, the less likely they were to report that premarital counseling
      had been available and voluntary, that it involved more hours of training, and
      that they had participated in it. However, the reported effectiveness of their
      premarital counseling experience was not significantly related to years since
      marriage. It is possible that even though the quality of premarital counseling
      may have improved over time, the challenges and complexity of marriage may have
      changed at a similar rate, resulting in no net change in the perceived
      effectiveness of such interventions.

PMID- 9230491
TI  - Construction of scales for the Center for Marital and Sexual Health (CMASH)
      Sexual Functioning Questionnaire.
AB  - The objective of this study was to identify a set of scales for summarizing the
      results of the Center for Marital and Sexual Health Sexual Functioning
      Questionnaire (CMASH SFQ). Scales for this instrument were constructed using
      patients' responses to the CMASH SFQ in a recent clinical trial of prostaglandin
      E1 (PGE1, alprostadil), an injectable vasodilator used to treat erectile
      dysfunction. A set of items was identified as a scale if they met predetermined
      standards of internal consistency, discriminant validity, and convergent
      validity. The reproducibility of the scales was then evaluated, and the extent to
      which the scales reliably measured change in treatment-related quality of life
      was assessed. Reliable and responsive scales for four domains related to sexual
      functioning were identified. Items in these scales were generally internally
      consistent; items in the scales and the scores for the scales generally satisfied
      criteria of discriminant validity; and the scales generally satisfied the
      standard for convergent validity. Evaluating patients' responses to the CMASH SFQ
      with scores for four reliable and responsive scales allows easier summarization
      of patients' sexual functioning and increases the statistical power of
      evaluations of the effects of interventions designed to improve sexual
      functioning.

PMID- 9230492
TI  - Therapeutic and iatrogenic interventions with adults who were sexually abused as
      children.
AB  - The field of sexual victimization and trauma has generated incompatible paradigms
      that confuse conceptualization, assessment, and treatment for adult survivors of
      child sexual abuse. It is crucial to be aware of potential iatrogenic concepts
      and interventions, especially those involving litigation, obscessing about past
      trauma, self-esteem as a victim, quest for external validation, identification
      with the victim movement, exploration of repressed memories as a goal in itself,
      and focus on the past at the expense of being a survivor in the present. Core
      therapeutic concepts are accepting oneself as a survivor; experiencing adult
      sexuality as voluntary, mutual, and pleasure-oriented, and feeling deserving of
      healthy sexuality; and focusing on living well in personal, sexual, marital, and
      parenting roles.

PMID- 9230493
TI  - Resolution of erectile dysfunction and inhibited male orgasm in a single
      homosexual male and transfer of inhibited male orgasm cure to his partner: a case
      report.
AB  - The following case study illustrates the treatment of a single male with an
      erectile dysfunction as well as an inability to achieve orgasm by partner
      stimulation. His partner also suffered from the latter dysfunction. Although we
      never saw his partner, we were able to cure both dysfunctions in the patient and
      reportedly his partner's difficulty as well.

PMID- 9230494
TI  - Pretending orgasm during sexual intercourse: correlates in a sample of young
      adult women.
AB  - Although popular media have addressed the issue of women pretending orgasm during
      sexual intercourse, the research literature on the phenomenon is sparse. In the
      current study, 161 young adult women provided data regarding lifetime sexual
      experience, objective and subjective physical attractiveness, sexual attitudes
      (erotophobia-erotophilia), sexual esteem, and general tendencies toward self
      monitoring of expressive behavior in social situations. Overall, more than one
      half of the women reported having pretended orgasm during sexual intercourse. In
      univariate analyses, the "pretenders" and "non-pretenders" did not differ in
      experimenter-rated facial attractiveness, self-rated body attractiveness, or
      general self-monitoring. However, pretenders were significantly older; viewed
      themselves as facially more attractive, reported having had first intercourse at
      a younger age; reported greater numbers of lifetime intercourse, fellatio, and
      cunnilingus partners; and scored higher on measures of sexual esteem and
      erotophilia. In multivariate analyses, only sexual esteem was uniquely related to
      having pretended orgasm. The findings are discussed with regard to possible
      explanations and implications, as well as directions for future research.

PMID- 9230495
TI  - Therapeutic implications of conservative clergy views on sexuality: an empirical
      analysis.
AB  - This research attempts to close the gap in the literature on clergy views of
      sexuality by surveying pastors of a large conservative evangelical denomination
      in a metropolitan southern California county (n = 31) on moral attitudes,
      understandings of God's view of sexuality, and the role of the church regarding
      issues of sexuality. These pastors held quite conservative moral principles while
      also affirming sensuality within the context of a marital relationship. Pastors
      saw the role of the church as mainly to serve and influence the sexual practices
      of the people within the church but also affirmed the church's involvement in the
      influence of the local community. Religion and sexuality were entirely compatible
      concepts for these pastors. Therapeutic implications and suggestions are offered.

PMID- 9230496
TI  - Erotomania following an orchiectomy: a case report.
AB  - A case report of young male patient with erotomania following seminoma and
      orchiectomy is described in this article. The probable dynamics that lead to this
      delusion are then discussed. This case report demonstrates the cooperation
      between the oncology ward and the psychiatric liaison service.

PMID- 9230497
TI  - Continuous measurements of intra-vascular pO2 in the pig optic nerve head.
AB  - BACKGROUND: The measurement of oxygen concentration in the microvasculature of a
      tissue is important for the understanding of oxygen delivery. MATERIAL AND
      METHODS: A technique was developed to measure in a continuous manner the partial
      pressure of oxygen (pO2) in the optic nerve microvasculature of the minipig. This
      technique is based on the quenching by oxygen of the phosphorescence emitted by a
      dye that is injected intravenously. It provides measurements of the intra
      vascular pO2 and was applied simultaneously with measurements of the extra
      vascular pO2 with microelectrodes and blood flow by laser Doppler flowmetry.
      RESULTS: We demonstrate for the first that the optic nerve head intra-vascular
      pO2 increases during dark adaptation. Furthermore no change in extra-vascular pO2
      and blood flow could be detected. CONCLUSIONS: Based on Krogh's model, these
      results suggest that oxygen consumption by the optic nerve head tissue increases
      during dark adaptation.

PMID- 9230499
TI  - Specific detection of mousepox virus by polymerase chain reaction.
AB  - Polymerase chain reaction was applied to the rapid identification and detection
      of mousepox virus. This was accomplished by selection of primers targeting the A
      type inclusion body protein gene. By investigating 20 strains belonging to five
      different species of the genus Orthopoxvirus, amplification was achieved only
      with the seven mousepox virus strains examined. The size of the resulting DNA
      fragment accounted for 116 base pairs and contained a recognition site for the
      restriction enzyme HindII, thus confirming its viral origin. Amplification of
      mousepox virus specific sequences was also possible from infected mouse lung
      tissue and serum.

PMID- 9230498
TI  - Microbiological monitoring of laboratory pigs.
AB  - Purpose-bred minipigs, are often used as the non-rodent species in toxicology.
      Infections may interfere with animal experiments, and there are no scientific
      reasons why the non-rodent species should be of a lower microbiological quality
      than the rodent species. Therefore, a system for health monitoring of pigs was
      developed in order to raise the quality of laboratory pigs to the level of
      laboratory rodents. This system, which includes screening for several viruses,
      bacteria and ecto- and endoparasites, was used for monitoring minipigs from a
      barrier unit with the same standards applied to rodents units. In these pigs only
      rotaviruses are found, which was shown by both serological antibody detection and
      by detection of rotaviral antigen in faeces. In minipigs from another unit with
      far less hygienic protection rotaviruses were also found along with certain
      influenza- and coronaviruses, as well as Pasteurella spp. It is concluded, that
      it is possible to raise pigs of a microbiological quality comparable to the
      quality of rats and mice, and that advanced microbiological monitoring in pigs
      will reveal useful information.

PMID- 9230500
TI  - Outbreaks of hyperkeratotic dermatitis of athymic nude mice in northern Italy.
AB  - Hyperkeratotic dermatitis of athymic nude mice is an infectious disease caused by
      a coryneform bacterium. During the spring of 1995, outbreaks of hyperkeratotic
      dermatitis were observed in several nude mice facilities in northern Italy. In
      this report we describe the clinical, histopathological and microbiological
      features of the disease in two different animal facilities. Affected animals
      showed a typical 'scaly' appearance with small white flakes of material adherent
      to the skin. In one of the outbreaks (facility 2) the lesions were less severe
      and involved only limited areas of the body. The infection spread very quickly
      and the morbidity reached more than 80% in a few days, while the mortality was
      about 1%. The lesions resolved spontaneously within 7-10 days. Histological
      examination of affected skin revealed orthokeratotic hyperkeratosis, acanthosis
      and dermal inflammatory infiltration which were more severe in mice from facility
      1. In Gram-stained sections groups of rods consistent with coryneform bacteria
      were detectable in the keratin layers covering the epidermal surface. A
      coryneform bacterium, biochemically typed as Corynebacterium bovis, was isolated
      from 11 out of 11 mice from facility 1 and from 8 out of 11 mice from facility 2.

PMID- 9230501
TI  - A serological indication of the existence of a guineapig poliovirus.
AB  - Attempts were made to clarify whether laboratory guineapigs may harbour a
      poliovirus which, in 1911, was described as the cause of a disease called
      guineapig lameness. By the use of ELISA for antibodies against the poliovirus,
      Theiler's murine encephalomyelitis virus (TMEV), it was shown that two pet shop
      guineapigs suffering from lameness had extremely high titres against poliovirus,
      while healthy guineapigs from the same pet shop were negative. Clearly positive
      results were also found in 35 out of 152 laboratory guineapig sera. Positive
      results were found in only two out of six breeding centres, but in three out of
      three experimental units, all of which purchased guineapigs from one of the
      seropositive breeding colonies. The diseased guineapigs recovered fully after
      treatment with vitamins in the drinking water, a treatment used for guineapig
      lameness by small animal practitioners. A theory that vitamin C deficient
      guineapigs are, due to an impaired steroid secretion, predisposed to succumbing
      to infection and develop demyelinating disease similar to that in TMEV infected
      mice is discussed briefly. Guineapig sera were also tested serologically for
      other infections. Antibodies against lymphocytic choriomeningitis virus,
      Clostridium piliforme and Toxoplasma gondii were not found, but one breeding
      colony was infected with adenovirus, pneumonia virus of mice, reovirus type 3,
      Sendai virus, parainfluenza (simian) virus type 5 and Encephalitozoon cuniculi.
      Two other breeding colonies were infected with both reovirus type 3 and E.
      cuniculi. In all three experimental units infection with adenovirus was observed,
      and in two of these Sendai virus and E. cuniculi antibodies were also found. The
      pet shop guineapigs were infected with adenovirus, reovirus type 3 and E.
      cuniculi.

PMID- 9230502
TI  - Transrectal ultrasound guided manipulation of the canine prostate with minimum
      intervention.
AB  - The canine prostate is a widely used and well established animal model for the
      assessment of therapeutic effects of laser technology in the search for better
      options for the treatment of benign prostatic hyperplasia. Conventionally for
      such experiments, the canine prostate is approached by laparotomy or
      transperineal urethrotomy. We have demonstrated a technique involving the use of
      ultrasound guided biopsy of the liver and prostate, and percutaneous laser
      treatment of the prostate, which has proved to be effective in reducing adverse
      effects on the experimental animals but without compromising scientific
      requirements for the experiments. We conclude that state-of-the-art percutaneous
      procedures not only refine animal intervention significantly but are also
      technically feasible for most laser studies using the canine prostate as an
      experimental model in the live animal.

PMID- 9230503
TI  - Portacaval shunt control animals: physiological consequences derived from the
      sham operation.
AB  - The portacaval shunt in the rat is a frequently used experimental model of
      portosystemic encephalopathy. Among other consequences of this surgical
      preparation is an important decrease in hepatic and testicular volume. Different
      sham-operation methods including a laparotomy were used as controls in each case.
      Given that the liver volume varies greatly in comparison to body weight in the
      sham-operated animals, this paper aims to evaluate the possible consequences of
      the sham operation. It concludes that control animals without manipulation, in
      addition to the respective controls of portacaval shunt, should be used in every
      case.

PMID- 9230504
TI  - Method for long-term intestinal access in the dog.
AB  - A variety of devices have been used to establish long-term intestinal access in
      laboratory animals. Their use is complicated by infection, tissue reaction, and a
      frequent need for single housing to prevent implant damage. Intussuscepted nipple
      valves have long been used in the human field of surgery for various applications
      where there is a need to create a reservoir without leakage. With the use of the
      nipple valve it was possible to establish long-term intestinal access in dogs
      with minimal post-operative complications, no leakage and, because no foreign
      material was used, no complications due to tissue rejection. The advantages of a
      nipple valve over the similar technique of a straight stoma is less postoperative
      complications in the form of leakage as well as enhanced access due to the design
      of the nipple valve. Encouraging results prompted us to widen the use of nipple
      valves to 14 dogs in which it has been possible to establish long-term colonic or
      duodenal/ileal access at one or two sites. Nine of the dogs are still in use with
      duration of instrumentation for some animals exceeding 60 weeks. This method
      requires minimal maintenance, does not prevent group housing of instrumented dogs
      or outdoor activities nor does it compromise the quality of life for the animals.

PMID- 9230506
TI  - A new hereditary cataract mouse with lens rupture.
AB  - A new cataract model originated in a recombinant inbred (RI) strain, CXS4 or CXSD
      (D), between BALB/cHeA(BALB/c or C) and STS/A(STS or S) mice. Opacity appeared as
      a white pinpoint focus in unpigmented eyes of albino mice from 5 weeks old. All
      the mice were bilaterally affected by 14 weeks old. They were fully viable and
      fertile. There was no sex difference in incidence of cataract. Histologically,
      the 3-4 months old mice showed vacuoles in the lens cortex. The vacuoles were
      spread all over the lens cortex in advanced cases. Ruptures of the lens nucleus
      to the vitreous chamber was a typical occurrence. For elucidation of the mode of
      inheritance, F1 hybrids (CXD and SXD) and backcross progenies [(CXD)F1XD and
      (SXD)F1XD] were analysed. No affected mice were observed in F1 hybrids. In
      backcross progenies, the segregation ratio of affected and normal mice was close
      to 1:1 in both matings. We conclude that the cataract is inherited by an
      autosomal single recessive gene. This mutant gene is provisionally named 'lens
      rupture 2' (gene symbol 1r2, Mouse Genome Database Accession No. MGD-JNUM-37399).
      The new cataract model mouse will be a good tool for the genetic analysis and
      molecular biological study of cataractogenesis.

PMID- 9230505
TI  - The Han:SPRD rat is not a genetic model of human autosomal dominant polycystic
      kidney disease type 1.
AB  - Human autosomal dominant polycystic kidney disease (ADPKD) is a high incidence
      disorder leading to renal failure in many patients. The majority of cases results
      from a mutation in the PKD1 gene. The only well documented animal model of ADPKD
      is the Han:SPRD-Pkd strain. Its genetic basis is unknown as yet. In the current
      study we determined whether the disease in these rats is genetically linked to
      the rat homologue of the PKD1 gene. We used the protamine gene as a polymorphic
      marker (Prm1) of the PKD1 region. Matings of Han:SPRD-Pkd with BB rats and
      backcross of the offspring with BB yielded animals informative for linkage
      analysis. This analysis revealed random segregation of the defect and the Prm1
      marker, indicating that the model is not caused by a mutation in the PKD1 gene.
      We conclude that the Han:SPRD-Pkd rat strain is not a genetic model of PKD1.

PMID- 9230507
TI  - The morphological changes of intestinal mucosa in growing rabbits.
AB  - The study aimed to increase understanding of digestive function from the
      development of the digestive tract from suckling to maturity in rabbits. The
      relative weights of the digestive tract (in relation to body weight) in different
      segments increase linearly during the rapid growth period between 2 and 8 weeks
      of age, thereafter intestinal weight gain is slower. An underdeveloped mucosal
      histology was observed in the hindgut of suckling rabbits at 2 weeks compared
      with 4 weeks of age. From SEM micrographs, the small intestinal mucosal villi
      look more slender and finger-like in the suckling period, thereafter becoming
      broader or tongue-like or plate-shaped in mature rabbits. The micrographs showed
      a compact arrangement in the underdeveloped hindgut mucosa at 2 weeks, but after
      weaning as hindgut fermentation becomes significant the mucosa increased in
      surface area.

PMID- 9230508
TI  - In vivo mucosal uptake, mucosal transfer and retention of iron in mice.
AB  - An improved and sensitive method for studying iron absorption in mice with
      alterations in body iron stores is described. Mice with varying iron status were
      given a double isotope-labelled test dose containing 59Fe and 51Cr as a non
      absorbable indicator, via an oroesophageal needle. Using a whole-body counter it
      was possible to measure in vivo the initial mucosal iron uptake and long-term
      iron retention and to calculate mucosal iron transfer. A significant difference
      was demonstrated between normal and both anaemic and dietary iron-loaded mice
      with regard to the various steps of iron absorption. When mice were tested twice
      for iron absorption, the results were highly reproducible. In conjunction with
      other parameters, the method described is useful in studying the mechanism and
      the regulation of iron absorption in mice.

PMID- 9230509
TI  - Orbital bleeding in rats while under diethylether anaesthesia does not influence
      telemetrically determined heart rate, body temperature, locomotor and eating
      activity when compared with anaesthesia alone.
AB  - The question addressed was whether orbital bleeding in rats, while under
      diethylether anaesthesia, affects their locomotor activity body core temperature,
      heart rate rhythm and eating pattern. Roman High Avoidance (RHA) and Roman Low
      Avoidance (RLA) rats were used to enhance generalization of the results. Orbital
      bleeding when the rats were under diethylether anaesthesia was compared with
      diethylether anaesthesia alone. To take into account any effects of handling, the
      rats were also subjected to sham anaesthesia. The RHA rats urinated more during
      anaesthesia, needed more time to recover from the anaesthesia and showed a
      greater endocrine stress response to diethylether anaesthesia when compared with
      the RLA rats. During anaesthesia, the RHA rats showed a greater fall of body
      temperature and bradycardia than did the RLA rats. Diethylether anaesthesia
      reduced locomotor activity in the RHA rats, but had no effect in the RLA rats. In
      neither RHA nor RLA rats did anaesthesia plus orbital puncture, versus
      anaesthesia alone, influence body temperature, heart rate rhythm, locomotor and
      eating activity. The lack of effect of orbital puncture occurred both in the
      short term (within 2h) and long term (within 48 hours) and thus this study
      indicates that orbital puncture had, at least with respect to variables measured
      in the present study, no effect superimposed on that of diethylether anaesthesia.

PMID- 9230510
TI  - Rapid increase in inspired desflurane concentration does not elicit a
      hyperdynamic circulatory response in the pig.
AB  - The effects of a rapid increase in inspired desflurane concentration on systemic
      haemodynamics and plasma catecholamines were studied in seven pigs (22-30 kg).
      Following premedication (flunitrazepam 0.4 mg/kg i.m.), anaesthesia was induced
      (propofol 2.5 mg/kg i.v., vecuronium 0.2 mg/kg i.v.), the trachea orally
      intubated, and ventilation controlled. Anaesthesia was maintained with N2O/O2
      (70%/30%), propofol (50 micrograms/kg/min), desflurane (2% end-tidal
      concentration), and vecuronium (0.3 mg/kg/h). After cannulation of both femoral
      arteries for subsequent simultaneous systemic pressure measurements and blood
      sampling for determination of epinephrine (E) and norepinephrine (NE) plasma
      levels, N2O and propofol were discontinued, and FiO2 and end-tidal concentration
      of desflurane increased to > 0.9 and 3%, respectively. Forty minutes later, the
      inspired concentration of desflurane was abruptly increased to 15%. Mean arterial
      pressure (MAP), heart rate (HR), and plasma concentrations of E and NE were
      determined before and 1, 2, 4, 8, 16, and 32 min after increasing the desflurane
      concentration. Plasma concentrations of E and NE were determined by high
      performance liquid chromatography (HPLC) with electrochemical detection. Data
      were analysed by repeated measures ANOVA (significance level P < 0.05). The
      abrupt increase in inspired desflurane concentration caused an insignificant
      increase (11%) in HR at 1, 2 and 4 min. There was an immediate decrease in MAP.
      Plasma levels of E and NE remained unchanged throughout. In conclusion, in
      contrast to findings in humans, a rapid increase in inspired desflurane
      concentration does not cause a hyperdynamic circulatory response in the pig.

PMID- 9230512
TI  - A strategy for abdominal pain.

PMID- 9230511
TI  - A medical reveals a slightly raised PSA.

PMID- 9230513
TI  - When you suspect abuse: what next?

PMID- 9230514
TI  - Key developments of the year in paediatrics.

PMID- 9230515
TI  - Childhood eczema: empowering the parent.

PMID- 9230516
TI  - When to treat the child who wheezes.

PMID- 9230517
TI  - Normal variant or orthopaedic abnormality?

PMID- 9230518
TI  - Easier communication with children.

PMID- 9230519
TI  - A new protocol for back pain.

PMID- 9230520
TI  - Thermal comfort properties of cotton and nonwoven surgical gowns with dual
      functional finish.
AB  - The purpose of this study was to evaluate thermal comfort properties of surgical
      gowns made of dual functional finish cotton and nonwoven fabrics which have
      barrier properties of blood and micro-organism. Four types of surgical gowns,
      which were made of nonwoven fabrics with finish or without and were made of
      cotton with finish or without, were tested. The thermal insulations of four
      surgical gowns were measured with thermal manikin. Subjective experiments on
      thermal comfort, skin temperature and clothing microclimate were conducted. Six
      male subjects, between 26 and 28 years age old, participated in the wear trials
      tests. Typical activities for surgeons in the operation theater were simulated
      during the experimental sessions. Air temperature in a climate chamber was kept
      at 22 degrees C and its humidity was 60% RH. Air velocity was controlled at less
      than 0.15 m/s. Inner radiant temperature was almost equal to the air temperature.
      Basic thermal insulation of the dual functional finished nonwoven surgical gown
      was 0.87 clo, which was slightly higher than that of untreated (0.84 clo).
      However, the skin temperature of the subject wearing a dual functional finished
      surgical gown was significantly lower at P < .05. When the subject wears the dual
      functional finished gown, the amount of sweating was less than that when wearing
      untreated. Microclimate temperature and humidity of dual functional finished
      surgical gown were lower than untreated and it was statistically significant.
      There was no significant difference in subjective humid and overall comfort
      sensation between finished and untreated ones. Thermal sensation of dual
      functional finished one was significantly different from untreated one only
      during the first exercise. The results of this study indicate that the dual
      functional finish surgical gown allowed heat to be transferred from the skin of
      subject to the atmosphere better than untreated. The nonwoven surgical gown
      showed no difference in comfort properties from cotton one.

PMID- 9230521
TI  - The effects of air mattress upon sleep and bed climate.
AB  - The purpose of this study was to investigate the effects of an air mattress upon
      sleep and bed climate. This air mattress, which employs a pump and timer to
      increase or decrease the inflation pressure in order to cure and prevent
      decubitus was tested. Six healthy female volunteers, aged 18 to 23, served as
      subjects. The experiments were carried out under three conditions: using regular
      Futon (Futon), the air mattress with pump and timer activated (Air+) and the same
      mattress without pump and timer activated (Air-). Room temperature and relative
      humidity were controlled at 22-23 degrees C and RH 50-60% respectively. Subjects'
      sleep was monitored by using EEG machine throughout the night, and subject's body
      temperature and bed climate were also continuously checked. Subjective estimation
      of bed and sleep were obtained before and after the recording sessions. Sleep
      onset latency and wake after sleep onset tended to be reduced in Air+ compared to
      Futon and Air-. The time and percentage of Stage 3 was increased significantly in
      the middle one third of the night in Air+. A significant difference was observed
      in bed climate of the waist area. Temperature tended to be higher in Futon than
      in Air+ and Air-, while relative and absolute humidity were significantly higher
      in Air+ and Air-. Significant difference between Air+ and Air- was observed only
      during one hour after sleep recordings started. Thermal sensation in the morning
      was cooler and comfort sensation tended to be better in Air+ and Air-. Subjective
      sleep estimation was somewhat good under all conditions. These results suggest
      that although these air mattresses do not affect sleep, we have to be cautious in
      using these mattresses as relative and absolute humidity were kept higher than
      with Futon. Further study on materials and construction of these air mattresses
      to decrease the humidity is needed.

PMID- 9230522
TI  - Effects of the morning irradiation of light with different wavelengths on the
      behavior of core temperature and melatonin in humans.
AB  - Following the previous studies on the influence of light with different
      wavelengths on human biological rhythms during nighttime, present experiments
      were conducted to investigate the influence of morning light on the behavior of
      the core temperature and melatonin in humans. The experiments were carried out in
      four subjects with normal color vision. The subjects were exposed between 4:00 h
      to 9:00 h to red, green and blue light of 1,000 lux and 2,500 lux, and with an
      incandescent light of 50 lux as control. The main results were as follows: No
      differences in the behavior of core temperature and melatonin were found under
      the influences of red, green and blue light of 1,000 lux and the control light of
      50 lux. On the other hand, a tendency to promote the increase of core temperature
      and the fall of melatonin secretion was found after exposure to green light of
      2,500 lux, compared with control and red light. These results indicate that the
      behavior of core temperature and melatonin differs according to the wavelength of
      light, and that the phenomenon arises with morning as well as nocturnal
      irradiation. However, the intensity of light required to bring about the
      phenomenon seems to be different between morning and evening; an irradiation of
      1,000 lux x 5h at night in the previous report, and one of 2,500 lux x 5h in the
      morning in the present experiments, were found to be necessary for green light to
      cause the effects.

PMID- 9230524
TI  - Interaction between auditory and visual processing in car audio: simulation
      experiment using video reproduction.
AB  - To clarify the effect of listening to music on the impression obtained from the
      landscape viewed from the car, a simulation experiment using video reproductions
      was conducted. The impression left by the landscapes and that of the music
      excerpts were measured by a semantic differential method. The impression of the
      landscapes is more pleasant when music excerpts are reproduced than when no music
      is presented. The pleasantness of the landscapes is the highest when relaxing
      music is being played. The impression of the landscapes is more powerful when
      music is present. In particular, agitated music has a strong effect to make the
      impression of the landscape more powerful. Music generally has an effect to
      'lighten' the landscape impression. However, very heavy music makes the landscape
      much heavier. Musical tempo is an important factor to determine the impression of
      music and affects the impression of landscape.

PMID- 9230523
TI  - Evaluation of evaporative heat transfer characteristics of helmets.
AB  - The prime purpose of a safety helmet is to protect against occupational hazards.
      However, thermal comfort is one important ergonomics requirement for a helmet to
      be accepted by its wearer. To design and manufacture a thermally comfortable
      helmet, a method for testing and evaluating the thermal properties is essential.
      Research has long focused on the evaluation of dry heat transfer (conduction,
      convection and radiation). Evaporative heat transfer was not much addressed. In
      order to analyze the wet heat transfer (evaporation) component, a sweating
      thermal head manikin has been used. In this study the method has been further
      improved by constructing a new sweating head manikin. The surface of the head
      manikin is divided into five zones which can provide more detailed information
      about the environmental effects on the heat transfer from the head when a helmet
      is worn. Water supply (simulated sweating) is also improved by use of an
      electronic pumping system which provides a steady and adjustable flow rate of
      water to the head manikin. Experiments were conducted within a climatic chamber
      with this improved method under different test conditions: the ambient
      temperature and the head manikin surface temperature are set at the same level:
      34 +/- 0.5 degrees C; two levels of head surface wettedness: 0.44 and 1.0; two
      levels of ambient humidity: 30% and 60%; and two levels of wind speed: 0.4 m/s
      and 1.0 m/s. Seven different helmets were used in the experiments. The results
      showed that the improved method revealed more detailed information about the
      evaporative heat transfer; it is easier to use and control; less error is
      involved with the measurement.

PMID- 9230525
TI  - Fused 2-thiohydantoin derivatives: evaluation as potential antioxidants.
AB  - A series of fused 5,5-diphenyl and 5-arylidene-2-thiohydantoin derivatives were
      examined for their oxygen free radical inhibitory and radical scavenging
      properties (RSC) using both an enzymic and non-enzymic biological generators of
      free radicals. Non-enzymic lipid peroxidation (OH. radicals) was assayed as the
      amount of malondialdehyde (MDA) that had been formed during incubation of boiled
      rat liver microsomes in the presence of ascorbic acid and ferric ions. Superoxide
      anions (.O2- anion radicals) were generated enzymatically in the xanthine
      xanthine oxidase system. Among the 20 investigated compounds only four fused
      arylidene 2-thiohydantoin derivatives showed weak antioxidant activity scavenging
      OH. radicals. There is a relationship between the electrophilic OH. radical
      scavenging properties (RSC) of the tested molecules and the value of their HOMO
      energy derived from semiempirical MO calculations.

PMID- 9230527
TI  - N-omega-carbethoxypentyl-4-quinolones: a new class of leukotriene biosynthesis
      inhibitors.
AB  - 6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed
      and synthesized as inhibitors of the production of arachidonic acid metabolites.
      The inhibitory activities were assayed in vitro by evaluation of serum
      leukotriene B4 and thromboxane B2 production. While all 6-[(4
      quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl
      4-quinolones, obtained as by-products in their synthesis, were found to be a new
      class of leukotriene biosynthesis inhibitors.

PMID- 9230526
TI  - Search for New Anticonvulsant Compounds, Part 2. Structure-activity relationship
      studies of new N-substituted amides of alpha-piperazine-gamma-hydroxybutyric acid
      as active anticonvulsants.
AB  - In a search for new anticonvulsants, two series of compounds, viz. derivatives of
      N-benzylamides of alpha-(4-phenylpiperazine)-gamma-hydroxybutyric acid (A) and
      derivatives of N-benzylamides of alpha-(4-benzylpiperazine)-gamma-hydroxybutyric
      acid (B), were investigated. These amides were obtained by aminolysis of 3-(4
      phenyl-, or 4-benzylpiperazine)-tetrahydrofuran-2-one with primary
      arylalkylamines (i.e. 2-phenylethylamine and 2,3,4-substituted derivatives of
      benzylamine). Preliminary pharmacological tests, a maximal electroshock (MES) and
      a subcutaneous metrazole (scMet), and a rotorod toxicity assay were employed. All
      compounds displayed anticonvulsant activity at range of doses 100-300 mg/kg in
      the MES screens. In order to point to some structural features correlating with
      the MES anticonvulsant activity crystal structure analysis followed by
      conformational analysis was carried out on two representative compounds of series
      A and B.

PMID- 9230528
TI  - New benzothiophene compounds related to propafenone.

PMID- 9230529
TI  - Small peptide libraries: combinatorial split-mix synthesis followed by
      combinatorial amino acid analysis of selected variants.
AB  - Peptides from small combinatorial libraries, covalently attached to polymeric
      TentaGel beads, can be directly sequenced using amino acid analysis. For
      libraries with restricted diversity, generated by the split-mix synthesis method,
      the amino acids on a selected single bead identified by pre-column derivatization
      with o-phthaldialdehyde (OPA) correlate directly with the sequence of a given
      peptide. This is shown on a tripeptide (343 different compounds) and a
      tetrapeptide (4096 different compounds) library. This method allows for rapid
      peptide sequence determination without relying on complex encoding strategies.

PMID- 9230530
TI  - Structure-activity relationships of sandalwood odorants: synthesis and odour of
      methyl-beta-santalol.
AB  - The synthesis and odour properties of the new santalol analogue, methyl-beta
      santalol, are described. The additional methyl group adjacent to the hydroxyl
      function of the standard molecule, beta-santalol, deprives the new compound of
      the sandalwood note. The synthesis and the odour evaluation of this compound
      supports the proposed model for sandalwood fragrance as it shows that the methyl
      group located at the osmophoric center prevents association of the molecule with
      the hypothetical receptor.

PMID- 9230531
TI  - Antibiotic resistance of Shigella spp., Salmonella spp., and Yersinia spp.
      isolated in Quebec.

PMID- 9230532
TI  - Shigella vaccine research and development.

PMID- 9230533
TI  - The contribution of recent advance in pediatric gastroenterology on child health.

PMID- 9230534
TI  - Current treatment of Helicobacter pylori infection and peptic ulcer disease.
AB  - Since the initial report by Warren and Marshall in 1984, Helicobacter pylori has
      assumed an increasingly important role in the pathogenesis of peptic ulcer
      disease and gastric carcinoma in all ages. A recent National Institutes of Health
      Consensus Development conference acknowledges the relationship between H. pylori
      infection and peptic ulcer disease and recommends that the medical community
      treat H. pylori infection in all patients with Helicobacter pylori and peptic
      ulcer. Although the same organism, the response to Helicobacter pylori infection
      in childhood differs somewhat from that seen in adults. The paediatric patient
      mounts a different inflammatory response, has different macroscopic appearances
      and has a markedly diminished peptic ulcer disease frequency compared with their
      adult counterparts. The appearances of antral nodularity appear to be
      characteristic of Helicobacter pylori infections. The appearances, however, are
      unrelated to symptoms and the underlying cause for this nodularity remains
      obscure. Younger children with peptic ulcer diseases are more likely to be
      Helicobacter pylori negative. This may suggest an increased susceptibility to
      gastric acid or possibly a very transient Helicobacter pylori infection rather
      than the well described lifelong infection without treatment. It is well known
      that the epidemiology of Helicobacter pylori would suggest that the incidence of
      infection increases with age. There is also geographical variations with the
      incidence being higher in countries of a third world background. These
      epidemiological observations fly in the face of all other infections where the
      major period of acquisition is in childhood. There has been recent evidence to
      suggest that in fact the incidence in childhood is decreasing in developed
      countries which could support the observation that there is a decreasing positive
      serology with successive decades in some countries. It is felt that the most
      likely mode of transmission to Helicobacter pylori is faecal to oral or oral to
      oral route. These are similar modes of transmission to Hepatitis A infections. It
      is obvious that most infections in childhood remain asymptomatic. It is also
      clear that there is no relationship between chronic recurrent abdominal pain of
      childhood syndrome and the presence of Helicobacter pylori infections. It remains
      to be seen as to who should be treated, what with and when. All of these issues
      will be discussed in the paper.

PMID- 9230535
TI  - Therapeutic endoscopy: removal of gastrointestinal foreign bodies in children.
AB  - Endoscopic removal of foreign bodies (FBs) is an important part of therapeutic
      endoscopy in children. The majority of FB ingestion occur in children under 5
      years. Children most often ingest coins, pins, keys, round stones or marbles,
      nails, rings, batteries and toys, and coins are the most common in the pediatric
      series of 139 children, who underwent endoscopic removal in Seoul National
      University, Children's Hospital. The management of FBs in children depends on the
      type (sharp or dull, pointed or blunt, and toxic or nontoxic) and the-size, along
      with the location of FB in the gastrointestinal tract. The endoscopist should
      decide whether endoscopic intervention is necessary and how urgently it has to be
      done. Indications for removal of FBs from the gastrointestinal tract in children
      are 1) all esophageal FBs. 2) gastric and duodenal FBs if they are sharp or
      pointed, if more than 4 cm long or 2 cm wide in young infants and children, if
      containing toxic substances and if blunt objects after 2 weeks observation in the
      stomach or 1 week observation in the duodenum. All FBs impacted in the esophagus
      should be removed within 24 hours because of the risks of perforation and serious
      fistula formation. Disk batteries can cause corrosive injury to the esophagus
      within 4 hours, and should be removed as soon as possible. Coin retrieval can be
      done very securely by the W-shape FB grasping forcep without an endotracheal
      general anesthesia. Blunt FBs, such as marbles can be best removed with a stone
      retrieval basket, which can be made from a condom. Disk batteries can not be
      grasped with the FB forceps and snares, but very safely with the powerful magnet
      attached to the tip of the scope. Overtubes and protective rubber hoods are
      useful for removing sharp or pointed objects. It is important to test the
      available grasping accessories on a duplicate of the FB as a "dry run" to
      determine which accessories will grasp the FB securely.

PMID- 9230536
TI  - A critical appraisal of current management practices for infant regurgitation.
AB  - Regurgitation is a common manifestation in infants below the age of one year and
      a frequent reason of counseling of general practitioners and paediatricians.
      Current management starts with postural and dietary measures, followed by
      antacids and prokinetics. Recent issues such as an increased risk of sudden
      infant death in the prone sleeping position and persistent occult gastro
      oesophageal reflux in a subset of infants receiving milk thickeners or thickened
      "anti-regurgitation formula" challenge the established approach. Therefore, the
      clinical practices for management of infant regurgitation have been critically
      evaluated with respect to their efficacy, safety and practical implications. The
      updated recommendations on the management of infant regurgitation contain 5
      phases: (1A) parental reassurance; (1B) milk-thickening agents; (2) prokinetics;
      (3) positional therapy as an adjuvant therapy; (4A) H2-blockers; (4B) proton pump
      inhibitors; (5) surgery.

PMID- 9230537
TI  - Clinical analysis of 22 infants with afebrile cluster seizures.
AB  - The inclusion criteria for afebrile cluster seizures in infancy are defined as
      follows: (1) frequency of afebrile seizures at least 2 episodes within 72 hours;
      (2) seizure onset between 2 months and 3 years of age; (3) excluding febrile
      convulsion, central nervous system infections, status epilepticus, well-known
      epileptic syndromes in infancy (e.g. early myoclonic encephalopathy, early
      infantile epileptic encephalopathy, benign myoclonic epilepsy, infantile spasms.
      Lennox-Gastaut syndrome), electrolyte imbalance, watery diarrhea, head injury and
      intoxication. From 1986 to 1996, retrospectively and prospectively 22 patients
      were collected who fulfilled the above criteria. Based on whether or not a strong
      family history was present and a history of mild diarrhea was associated with
      seizure onset, they were divided into three groups: Group I, benign infantile
      familial convulsions (4 patients); Group II, cluster seizures with mild diarrhea
      in infancy (5 patients); Group III, cluster seizures without diarrhea in infancy
      (13 patients). Before seizure onset and during follow-up, all of the patients had
      normal development. The seizure pattern in all was generalized, most tonic type
      with duration of seizure less than five minutes in the majority. Recurrence rate
      was 100% in Group I and no recurrence in Group II. In 16 patients who were
      seizure-free over 12 months, the duration of persistence varied from 1 day to 8
      months, and was shortest in Group II (range, 1 to 3 days). It was concluded that
      the vast majority of afebrile cluster seizures in infancy are benign in nature.
      Whether anticonvulsant therapy is justified must be individualized.

PMID- 9230538
TI  - Anterior cerebral artery Doppler ultrasonography for prediction of outcome after
      perinatal asphyxia.
AB  - During a five-year period, 47 term neonates with a history of asphyxia were
      investigated on the first day of life using intracranial Doppler ultrasonography
      to measure the Pourcelot resistance index (RI) of anterior cerebral artery.
      Another 30 healthy term neonates were also studied as controls. The results
      showed no significant differences in the gestational age and birth body weight
      between these two groups. However, the RI value of the Asphyxiated Group was
      significantly lower than that of the Control Group (mean +/- SD: 0.61 +/- 0.09 vs
      0.71 +/- 0.03, respectively). End diastolic flow velocity (mean +/- SD: 10.8 +/-
      3.1 vs 8.8 +/- 1.4 cm/sec) and mean flow velocity (mean +/- SD: 18.0 +/- 4.2 vs
      15.6 +/- 2.1 cm/sec) of the Asphyxiated Group were significantly higher than
      those of the Control Group. The asphyxiated patients were divided into three
      groups according to RI values. There were significant differences among Group A
      (RI < 0.55). Group B (0.55 < or = RI < 0.6) and Group C (RI > or = 0.6). These
      patients were followed up clinically for 15 to 65 months (mean: 39 months).
      Twenty patients in the Asphyxiated Group had neurodevelopmental delay with mild
      to moderate handicaps, whereas none in the Control Group had neurological
      sequelae in the follow-up period. This study demonstrates that, on the first day
      of life, a low RI value for asphyxiated neonates is associated with an adverse
      prognosis and may be considered as one of the earliest indicators for poor
      neurodevelopmental outcome.

PMID- 9230539
TI  - Long QT syndrome in children.
AB  - Long QT syndrome is a disease that can cause syncope, seizures and sudden death.
      From June 1990 to June 1996, 11 children (male/female: 714; ages: 1 day-13 years
      with a median of 5.4 years) from different families were found to have long QT
      syndrome. Their corrected QT intervals (QTc) were 0.46-0.59 sec (median: 0.53
      sec). All patients had normal hearing. One patient had Marfan syndrome with
      mitral valve prolapse. The presentation symptoms were: sudden death (2), seizures
      (6) and syncope (3). Their electrocardiogram abnormalities included: torsades de
      pointes (7), sinus bradycardia (4), T wave abnormalities (4), monomorphic
      ventricular tachycardia (2) and congenital complete atrioventricular block (1).
      All patients were treated with beta-blockers and one had pacemaker implantation.
      In a follow-up period of 0.5-6 years, 6 were symptom free, 1 died of ventricular
      tachycardia and 2 had recurrent syncope.

PMID- 9230540
TI  - Real-time ultrasonography of the pancreas in normal Chinese children in Taiwan.
AB  - The real-time ultrasound images of the pancreas in 142 children without clinical
      or laboratory evidence of pancreatic disease prospectively were analyzed to
      determine normal pancreatic size in Chinese children in Taiwan. Sonographic
      examinations of the pancreas were performed by sagittal scanning at the
      epigastrium; the long axis and short axis of the oval cross-sections of both the
      pancreatic head and body were measured. The relationships between pancreatic
      dimensions and body height, body weight, surface area and age were evaluated with
      linear regression analysis. Correlations with body height and age were better
      than those obtained with body surface area and body weight. Since all the
      physical parameters had better correlations with the long, rather than the short,
      axis of the pancreas, this indicated that the growth of the pancreas in children
      is primarily in the craniocaudal direction rather than the anteroposterior
      direction.

PMID- 9230541
TI  - Cutis marmorata telangiectatica congenita: report of one case.
AB  - Cutis marmorata telangiectatica congenita is an uncommon, congenital cutaneous
      lesion. It is usually present at birth, and is characterized by persistent fixed,
      flat, blue-violet cutaneous marmorata, telangiectasia, and phlebectasia.
      Frequently, there is associated skin atrophy and ulceration. There is an
      association with other abnormalities in at least 50% of the patients with cutis
      marmorata telangiectatica congenita. Thus, obtaining a thorough history and
      detailed physical examination are needed. We present a 38-day-old female infant
      with cutis marmorata telangiectatica congenita, with uneven growth of bilateral
      lower limbs, and review the literature on this rare lesion.

PMID- 9230542
TI  - Lipomyelomeningocele associated with necrotizing enterocolitis in a term neonate.
AB  - A six-day-old full-term female infant with lipomyelomeningocele, confirmed by
      magnetic resonance imaging, suffered from necrotizing enterocolitis (NEC) when he
      was four-day-old. The clinical presentations were bloody stool and abdominal
      distension. A plain abdominal film demonstrated pneumatosis intestinalis and air
      in the portal vein. An emergent laparotomy was performed and revealed diffuse
      gangrenous change of both small and large bowels. A jejunostomy was done and
      strong antibiotics were given, but the baby died two days after the operation. In
      this paper report, the relation between lipomyelomeningocele and NEC is
      discussed.

PMID- 9230543
TI  - Endocarditis due to Neisseria sicca: report of one case.
AB  - Many species of the Neisseria, which are respiratory commensals in humans, have
      been regarded as being nonpathogenic or as causing disease in only
      immunocompromised hosts. We report a case in which Neisseria sicca was the cause
      of infective endocarditis in a child with a ventricular septal defect and review
      the literature on endocarditis due to N. sicca infection. Most of these patients
      had an underlying heart disease. Dental caries and poor oral hygiene may be two
      factors that predispose patients to the infection. N. sicca endocarditis usually
      results in a subacute onset of symptoms and, if not diagnosed early and treated,
      is associated with a high rate of embolic complications.

PMID- 9230544
TI  - Bronchial stenosis mimicking the scimitar syndrome: report of one case.
AB  - The scimitar syndrome, also known as hypogenetic lung syndrome, has the classic
      radiological appearance of hypoplasia of the right lung, dextroposition of the
      heart, and a curvilinear density in the right lower lung that courses to the
      right cardiophrenic angle known as a scimitar sign. We report a case with
      stenosis of the main stem of the left bronchus and an emphysematous change of the
      left lung which shifted the heart to the right side and compressed the right
      lung. A curvilinear density was also noted in the right lower lung field. All
      these radiological findings together mimic the chest radiographic appearance of
      the scimitar syndrome.

PMID- 9230545
TI  - Robinow syndrome: report of one case.
AB  - We report a 2-month-old infant with Robinow syndrome. Clinical manifestations
      included short stature, characteristic facies, mesomelic brachymelia,
      brachydactyly, camptodactyly, duplication of thumbs, hypoplasia of clitoris, and
      deformed pronated foot. A cytogenetic study revealed a normal female karyotype.
      Chest radiography showed rib anomalies, a vertebral anomaly in T8, narrowing of
      interpedicular distances and flaring with slight thickening of the bone cortex in
      the bilateral humeral bone. Hand and foot radiography showed generalized
      shortening include unequal size of metacarpal, metatarsal and phalangeal bones.
      In our case, sporadic or autosomal recessive inheritance was most likely. The
      literature is reviewed.

PMID- 9230546
TI  - Implications of genetic research for medical practice and education.

PMID- 9230547
TI  - Information technology in the health care industry.
AB  - The health care information systems market has grown to a multibillion dollar
      industry, with a predicted average annual growth rate of 12% through the year
      2000. This paper provides an overview of information and management technology
      applications in health care for (a) medical diagnosis and treatment; (b) health
      care administrative functions; and (c) special applications of information
      technology to health care problems.

PMID- 9230548
TI  - Temporal trends in maternal characteristics and pregnancy outcomes: their
      relevance to the provision of health services. Hawaii, 1979-1994.
AB  - This paper examines changes in maternal sociodemographic characteristics and
      pregnancy outcomes in Hawaii during the period 1979-1994. The more striking
      changes were increases of 129% in the proportion of births to women > 35 years
      old and of 67% in the proportion of births to unmarried mothers. The percentage
      of low birth weight and small-for-gestational age infants decreased while the
      proportion of premature births increased. Identified changes were not limited to
      selected population groups, but were found in various degrees in all ethnic
      groups. These findings are relevant to all health practitioners and will assist
      in the provision of appropriate care and counseling to individual women.

PMID- 9230549
TI  - Irish guidelines for surgeons in the management of breast cancer. Irish Society
      of Surgical Oncology.

PMID- 9230550
TI  - The psychiatric and social background to suicide--the problem of prevention.

PMID- 9230551
TI  - Fibromyalgia syndrome.

PMID- 9230552
TI  - Fishing around for genes with fluorescence in situ hybridisation (FISH):
      applications in clinical genetics.

PMID- 9230553
TI  - Tuberculosis mortality--deaths with, rather than from tuberculosis?

PMID- 9230554
TI  - The National Maternity Hospital casualty department--a review.
AB  - This is a review of obstetrical and gynaecological patients presenting to our
      maternity unit after clinic hours from 1991 to 1993. Patient data was collected
      prospectively. The number of patients seen after clinic hours increased by 35%,
      from 2241 in 1991, to 3014 in 1993. Analysis of data from 1991 revealed that the
      majority of patients were self referred, General Practitioner referrals
      accounting for only 9% of patients seen. Antenatal patients were the largest
      group at 77%, 10% were postnatal and 13% had gynaecological complaints. Unbooked
      patients presenting with first trimester bleeding accounted for one third of all
      antenatal patients. Thirty eight percent of patients seen were admitted. The
      number of out-of-clinic hours patients constituted a sizeable proportion of our
      hospital population. We conclude that this service is a necessary and important
      part of patient care at a large maternity unit.

PMID- 9230555
TI  - Stercoral perforation associated with parathyroid adenoma.
AB  - We describe the case of a patient who presented with stercoral perforation of the
      sigmoid colon in association with hypercalcaemia caused by a parathyroid adenoma.
      Colonic resection was followed by successful parathyroidectomy and resulted in a
      satisfactory outcome. This unusual association is discussed.

PMID- 9230556
TI  - Lateral and anterior reciprocal electrocardiographic changes: relationship to ST
      segment elevation and underlying coronary artery disease in inferior myocardial
      infarction.
AB  - The electrocardiogram in patients with acute inferior myocardial infarction
      frequently displays ST depression in non-infarct leads. The significance of this
      finding is uncertain. The relationship between ST depression, ST elevation and
      arteriographic severity of coronary artery disease was explored. 22 patients with
      acute inferior myocardial infarction, receiving thrombolysis and undergoing acute
      (within seven hours of the onset of chest pain) coronary angiography were studied
      prospectively. The electrocardiographic ST segment elevation in the inferior
      leads and ST segment depression in the lateral and in the anterior precordial
      leads were measured. In each group of leads, the maximum value of ST deviation in
      any lead as well as the sum of the values for ST deviation in the individual
      leads was determined. Gensini scores of total coronary artery disease and
      component scores for the major coronary arteries were determined from the
      coronary arteriogram. There was a strong correlation of maximum inferior ST
      elevation with both maximum lateral ST depression (r = 0.96, p < 0.001) and with
      maximum anterior precordial ST depression (r = 0.78, p < 0.001). The
      corresponding correlations for sum of ST deviations were r = 0.91, p < 0.001 and
      r = 0.79, p < 0.001 respectively. There was no relationship between Gensini
      scores of coronary artery disease and measures of electrocardiographic ST segment
      depression or elevation. Electrocardiographic ST depression in non-infarct leads
      in patients with inferior myocardial infarction, does not provide information
      regarding the degree of coronary artery disease. The ST depression in both
      lateral and anterior precordial leads correlates with and is a reflection of
      inferior ST elevation.

PMID- 9230557
TI  - Renal revascularisation by gastroduodenal-renal bypass as treatment of renal
      artery stenosis.
AB  - We report the case of a 63 year old hypertensive male who presented with acute
      renal failure following treatment of his hypertension with the ACE antagonist,
      captopril. He was documented to have bilateral renal artery stenosis, which was
      treated by left renal artery angioplasty and revascularisation of the right
      kidney by anastomosis of the right renal artery to the superior gastroduodenal
      branch of the hepatic artery. Postoperatively, he made an excellent recovery,
      with restoration of his renal function to normal and improved control of his
      hypertension.

PMID- 9230558
TI  - Recurrent life-threatening thrombocytopenia in a patient with chronic "Parstelin"
      dependence.
AB  - Several cases of Tranylcypromine dependence have been reported, with a typical
      profile emerging. We describe a woman with a chronic dependence on the drug
      combination "Parstelin" who develops a recurrent severe thrombocytopenic purpura.

PMID- 9230559
TI  - Childhood accidents at home.
AB  - Accidents are the leading cause of death in children and a major factor in lost
      productive life. This case-control study investigates childhood accidents in the
      home by randomly surveying children presenting to a Dublin Accident and Emergency
      Department. Risk factors for home accidents are examined by comparing cases
      (those with accidental injuries sustained at home) with controls. Of the 174
      accident attenders, 59.2% were boys; 66% of all surveyed were under 5 years.
      Cases were more likely to belong to Social Class 5-6 (P < 0.01), their fathers
      were less likely to be employed (p < 0.01) and mothers were less likely to be
      working outside the home (P < 0.01). Over 50% of injuries were due to falls
      (50.8%). Blows and cuts accounted for 22.6% of injuries, while 13% were due to
      burns, 7.9% were due to poisoning, and 5.7% due to foreign bodies. Children under
      5 were more likely than older children to have been supervised at the time of the
      accident. Most of the injuries were minor. However, 34 children (19.5%) required
      hospital admission. Measures to prevent accidents at home should be targeted
      towards those at most risk-parents of pre-school children and the lower social
      class groups. Accident prevention requires a three-pronged approach i.e.
      environmental change, enforcement of legislation and educational measures.

PMID- 9230560
TI  - 'Saturday flit, short sit'--a strong influence of a superstition on the timing of
      hospital discharges?
AB  - 'Saturday Flit, Short Sit' is a phrase recognised by 58% of our patient
      population. The superstition implies that leaving hospital on a Saturday is bad
      luck and will mean early re-admission to hospital. 13.7% of all patients
      interviewed would refuse to go home on a Saturday and 40% of doctors would allow
      postponement of discharge because of the patients superstition.

PMID- 9230561
TI  - Knowledge and attitudes to prescribed drugs in young and elderly patients.
AB  - Increasing patient knowledge of drug therapy is said to improve compliance and
      may reduce adverse drug reactions. We assessed patient knowledge of prescribed
      drugs in fifty patients attending a hypertension clinic [outpatients] and in
      elderly patients on admission to (n = 129) and on discharge from (n = 100) an
      acute geriatric assessment unit. We found that 88% of outpatients, 40% of elderly
      admissions, and 41% of elderly discharges knew the indications for their therapy;
      only 40% of outpatients, 8% of elderly admissions and 12% of elderly discharges
      could name their medications. Patients said that their information came
      principally from the prescribing doctor. In a further study we assessed doctor,
      nurse, young and elderly patients' ability to discriminate between commonly
      prescribed white tablets. Errors were made by the doctors on 25% occasions,
      nurses on 40% occasions and patients on 61% occasions. Young patients made errors
      67% of the time and elderly patients 55% of the time. These studies indicate that
      both inpatients and outpatients, both young and elderly have poor knowledge of
      their medications. In addition, many commonly prescribed drugs are not easily
      distinguishable by patient, prescriber or drug administrator. We conclude that
      there is a need to improve knowledge both in patients and in prescribers. We
      suggest that prescribers should consider the colour and shape of medications
      prescribed concurrently as many "little white tablets" are difficult to tell
      apart.

PMID- 9230562
TI  - Diabetes mellitus in childhood cystic fibrosis.
AB  - Since 1984, five patients in the cystic fibrosis (CF) clinic at Cork Regional
      Hospital have developed diabetes mellitus (DM) and were treated with Insulin.
      None had received systemic corticosteroids but two had high calorie naso-gastric
      feeding regimes. Two died from lung disease. A fifteen year old boy developed
      bilateral cataracts. In nine other paediatric CF clinics in the Republic of
      Ireland (total: 420 patients), three patients have DM, two receiving Insulin.
      Abnormal glucose tolerance is becoming more common in CF as patients survive
      longer. The possible role of corticosteroid treatment and intensive carbohydrate
      feeding regimes in development of glucose intolerance must be considered. DM in
      CF differs from the usual childhood DM. Regular screening and early Insulin
      supplementation may be beneficial.

PMID- 9230563
TI  - Patterns of inheritance in Irish and Italian families with neural tube defects:
      comparison between high and low rate areas.
AB  - Neural tube defects (NTDs) may result from a genetic susceptibility interacting
      with environmental exposures occurring early in pregnancy. Current research is
      concerned with enlarging our understanding of the action of folic acid, a B group
      vitamin, which has been shown to prevent the occurrence of NTDs in clinical
      trials. Despite the epidemic waves in the incidence of NTDs and the existence of
      areas with very high rates, there have been few studies that explored the genetic
      contribution to NTDs in high rates versus low rate areas. We investigated the
      genetic epidemiologic factors that occur in NTD families and compared their
      frequency in a high rate area-Ireland-with a low rate area-Italy. We explored the
      existence of three features indicative of hereditary factors and found that all
      three factors were higher in Ireland than in Italy. These factors were (i)
      sibling recurrence risk (3.3% vs 1.6%; p = 0.2), (ii), other malformations in
      siblings (11.5% vs 3.3%; p < 0.001) and (iii) average number of children in
      mothers' families vs fathers' families (average difference in Ireland 1.0 vs 0.4
      in Italy; p < 0.1). These results support the motion that geographic differences
      in occurrence of NTDs are due at least in part to differing prevalences of
      genetic susceptibility factors. Further epidemiological and molecular studies are
      needed to confirm this observation. In addition, studies of the interactions
      between environmental agents and genetic susceptibility will be important in
      determining their relative contributions.

PMID- 9230564
TI  - Evaluation of Ames DCA 2000 for the rapid measurement of HbA1c in an outpatient
      clinic.
AB  - Comparison of the Ames DCA 2000, a new device for the rapid measurement of HbA1c,
      with the established laboratory method (Dako HbA1c system) was made in 58
      children routinely attending a diabetic outpatient clinic. Results showed that
      DCA 2000 and laboratory estimations of HbA1c were closely correlated throughout
      the range of values (R = 0.95). The mean difference between values was 1.83% with
      a 95% range of agreement of 0.23-3.4%. The DCA 2000 can be used to provide a
      rapid estimate of HbA1c upon which decisions on changes in treatment can be based
      at diabetic clinics.

PMID- 9230565
TI  - Invermectin and the environment.

PMID- 9230566
TI  - N-acetylcysteine (NAC)--a safe antidote in paracetamol poisoning?

PMID- 9230567
TI  - Silicone breast implants. Can emerging medical, legal, and scientific concepts be
      reconciled?

PMID- 9230568
TI  - Human experimentation. Protecting patient autonomy through informed consent.

PMID- 9230569
TI  - A global measure of access to mental health services for a managed care
      environment.
AB  - The growing influence of managed care in mental health services has raised
      important questions about access to services. This article introduces and
      demonstrates a global measure of access that is based on the relationship between
      service utilization and the need for services. This measure has become practical
      because of recent advances in measurement technology that provide more valid and
      reliable estimates of the prevalence of mental illness in general populations and
      of the number of people who receive mental health services across service
      sectors. The methodology is used to produce a report card type profile of access
      to inpatient mental health services (in state, general, private, and veterans
      hospitals) by residents of one state. This global measure can provide a powerful
      and efficient tool for monitoring and comparing the impact of managed care plans
      on access to mental health services.

PMID- 9230570
TI  - Use of the Child and Adolescent Functional Assessment Scale to predict service
      utilization and cost.
AB  - The Child and Adolescent Functional Assessment Scale (CAFAS) is a
      multidimensional measure of impairment that assesses the extent of interference
      in day-to-day functioning secondary to emotional, behavioral, or substance use
      problems. Respondents were 984 youths, aged 5 to 17, who were referred for mental
      health services. They were assessed at intake and at 6 and 12 months postintake
      with a battery of measures administered by evaluation staff who were independent
      of treatment. Utilization indicators included restrictiveness of care, total
      cost, number of bed days, and total number of days of service received. The CAFAS
      total score at intake was a significant predictor of service utilization and cost
      determined at 6 and 12 months postintake. The CAFAS score was also the best
      predictor when compared with other measures of psychopathology. Only the CAFAS
      and presence of conduct disorder contributed to the prediction of service
      utilization and cost at 12 months.

PMID- 9230571
TI  - Housing costs for adults who are mentally ill and formerly homeless.
AB  - The goal of this study was to evaluate the costs, under two different housing
      conditions, to the state mental health agency of caring for adults who are
      homeless and mentally ill. One hundred and twelve clients of the Massachusetts
      Department of Mental Health, living in psychiatric shelters, were randomly
      assigned to one of two housing types: Evolving Consumer Households or Independent
      Living apartments. For the next 18 months each client was followed so that the
      cost of treatment, case management, and housing could be collected and compared.
      The authors found that treatment and case management costs did not vary by
      housing type, but housing costs were significantly higher for those assigned to
      Evolving Consumer Households. Regardless of original housing assignment,
      treatment costs were lower for clients who remained where they were originally
      placed. The authors conclude that providing support for clients that increases
      housing stability reduces their need for treatment and that independent living
      arrangements may be a more cost-effective policy choice.

PMID- 9230572
TI  - Conceptualizing services research on outpatient commitment.
AB  - Issues affecting the research of outcomes of involuntary outpatient commitment
      (OC) of persons with serious mental illness are explored. These issues include
      the reliance on hospital recidivism as a primary measure of outcome, the role of
      family members and coercion in the process of outpatient commitment, and the
      conceptualization and design of studies. A conceptual framework that attempts to
      incorporate responses to these issues is proposed. Continued research on OC
      should build on conceptual models that include family role and burden, services
      delivered, an accounting for varied coercive mechanisms, and client-level
      outcomes. Rehospitalization should be conceptualized as an intermediate variable
      between OC and client-level outcomes rather than as an ultimate outcome.

PMID- 9230573
TI  - Measuring treatment outcome for adults and adolescents: reliability and validity
      of BASIS-32.
AB  - This article examines the reliability and validity for adults and adolescents of
      Behavioral and Symptom Identification Scale (BASIS-32), a 32-item patient-report
      instrument designed to facilitate psychiatric outcome assessment of adult
      inpatient populations. This study extends the original analysis of the
      psychometric properties of BASIS-32 to a different site, using a self-report
      rather than interview format and samples of both adult and adolescent patients.
      Responses to the BASIS-32 are reported for two groups of patients consecutively
      admitted between 1991 and 1994: adults over 18 years old (n = 462) and
      adolescents between 12 and 18 (n = 244). Results of this investigation confirm
      the utility of BASIS-32 as an easily administered and scored self-report outcome
      assessment tool for adult psychiatric patients. Its utility for adolescent
      patients was not as clearly demonstrated.

PMID- 9230574
TI  - An exploratory study of male recovering substance abusers living in a self-help,
      self-governed setting.
AB  - Adult men (n = 132; 92% of the population) with histories of alcohol/drug use
      disorders were interviewed upon their entry to 11 Oxford Houses located in the
      state of Illinois. Individuals still in residence at a six-month follow-up (n =
      48) were reinterviewed; prior to the follow-up interview, 42 men had left
      voluntarily and 42 men had been evicted for abuse or disruptive behavior. The men
      remaining in residence tended to be older (M age = 37 years), were
      disproportionately African American (56%), and were less pessimistic about their
      future. At the intake interview, individuals who would be evicted reported a
      lower expectation for abstinence social support from the other residents in
      Oxford House. The Oxford House model of social support for recovery from alcohol
      and drug dependence appears to help some residents maintain sobriety.

PMID- 9230575
TI  - An economic and clinical rationale for changing utilization review practices for
      outpatient psychotherapy.
AB  - The growth of managed care has led to greater cost consciousness in the financing
      and delivery of mental health and substance abuse services. The authors examine
      whether pressures to reduce the costs associated with mental health and substance
      abuse treatment have led to the overapplication of a popular managed care
      strategy, utilization review (UR), to the management of outpatient psychotherapy
      benefits. Several arguments are presented highlighting why changing outpatient
      psychotherapy UR practices would be in the best economic and clinical interests
      of all involved parties, including payers, managed care organizations (MCOs),
      mental health consumers, and providers. A number of alternatives to the
      aggressive management of outpatient psychotherapy benefits are outlined and
      discussed.

PMID- 9230576
TI  - Suicide risk factors among veterans: risk management in the changing culture of
      the Department of Veterans Affairs.
AB  - Suicide risk management in the Department of Veterans Affairs (VA) health care
      system is particularly challenging because of both patient characteristics and
      aspects of the delivery system. The prototypical suicide-prone person is an older
      white male with alcoholism, depression, physical problems, and poor psychosocial
      support. This describes a large portion of the veteran patient population.
      Suicide risk factors that are common in VA patients include male gender, older
      age, diminished social environment support (exemplified by homelessness and
      unmarried status), availability and knowledge of firearms, and the prevalence of
      medical and psychiatric conditions associated with suicide. A variety of
      characteristics of the VA system complicate suicide management. Efforts under way
      to emphasize ambulatory care and decrease the VA culture of reliance on inpatient
      treatment heighten the importance of accurate suicide assessment. The authors
      recommend several strategies that VA administrators can consider for improving
      the assessment and management of veterans with long-term suicide risk factors.

PMID- 9230577
TI  - Managing depression in general practice in Pakistan: do we need to re-invent the
      wheel?

PMID- 9230578
TI  - Evaluation of adrenal function in long standing pulmonary tuberculosis: a study
      of 100 cases.
AB  - Tuberculosis is a major public health problem in Pakistan and adrenal involvement
      in long-standing tuberculosis has been found to be common. A multi-center study
      was conducted to assess the adrenal function using short Synacthen test in one
      hundred patients with tuberculosis of more than 6 months duration at three
      hospitals of Rawalpindi and Islamabad. Forty patients demonstrated impaired
      response to Synacthen test. In 21 (52.5%) the increment from basal level was less
      than 300 nmol/L with a peak level increasing to over 600 mmol/L in 15 (37.5%)
      patients, the increment from basal level was less than 300 nmol/L as well as the
      peak level was also less than 600 nmol/L. In 4 (10%) patients the increment was
      more than 300 nmol/L but they were not able to obtain a peak level of 600 nmol/L.
      No significant difference was found between the patients with normal response and
      the impaired response with regards to their clinical features, duration of
      illness, body mass index (BMI), blood pressure variation and routine biochemical
      profile. It is concluded that adrenal dysfunction is common in patients with long
      standing tuberculosis. Diagnosis of hypoadrenalism is not possible on clinical
      grounds and routine biochemical examinations. Synacthen stimulation test is
      necessary for its diagnosis.

PMID- 9230579
TI  - Genetic markers and duodenal ulcer.
AB  - Serum pepsinogen, alpha 1-antitrypsin (alpha 1-AT) and blood groups were studied
      as genetic markers in 32 patients with endoscopically proven duodenal ulcer and
      44 control subjects with no family history of ulcer disease. Serum pepsinogen was
      determined by the modified method of Edward et al, alpha 1-AT by single radial
      immunodiffusion (RID) and phenotyping was carried out by isoelectric focusing
      (IEF). Duodenal ulcer patients with hyper- pepsinogenemia (28%) and low serum
      alpha 1-AT (35%) had a dominant blood group O, lower mean age, an early onset of
      disease, a higher frequency of gastrointestinal (GI) bleeding and ulcer
      perforation. These parameters were found considerably different in patients with
      normal serum pepsinogen and alpha 1-AT. Phenotype analysis of alpha 1-AT revealed
      that four duodenal ulcer patients had partial deficiency of the protease
      inhibitor and none of the normal exhibited the deficiency pattern. The etiology
      of the disease appears to be genetic anomaly in 28% of patients while the rest
      (72%) had ulcers as a result of neuroendocrinological or environmental factors.

PMID- 9230580
TI  - Bone marrow changes in human malaria: a retrospective study.
AB  - The bone marrow reports of 1966 patients admitted to a provincial teaching
      hospital between January, 1992 to April, 1995 were retrospectively analyzed.
      Twenty-six (1.3%) bone marrows showed the presence of malarial parasites. Sixteen
      (62%) patients had Plasmodium falciparum 9 (34%) Vivax malaria and one (4%) mixed
      infection. All these patients gave a history of prolonged illness and had low
      parasite counts. Plasmodium vivax malaria was not associated with any significant
      pathology in the bone marrow, except iron deficiency anaemia. The bone marrows
      with Plasmodium falciparum malaria showed myeloid hyperplasia, erythroid
      hyperplasia, megaloblastosis and hypoplasia in different proportions. No evidence
      of dyserythropoiesis was found in this series. The possible mechanisms producing
      these changes and the factors responsible for the discrepancy in bone marrow
      findings in different geographical areas are discussed.

PMID- 9230581
TI  - Efficacy and safety of mebendazole in children with worm infestation.
AB  - Children aged between 2-16 years, were screened for worm infestation. Fifty-five
      children fulfilling the inclusion criteria were included in the study. They were
      treated with mebendazole 100 mg twice daily for three consecutive days and
      followed-up for 15 days to assess cure rate and side effects. Fifty children
      completed the study with their stools being tested by direct smear and
      concentration methods and blood CBC done before treatment and at the end of the
      study. The cure rate for ascaris was 100% and for trichuris 75%. The drug was
      well tolerated and apart from mild diarrhoea occurring in 22% children, no
      untoward effects were reported. Nemazole (mebendazole) has shown promise and
      seems useful in treating children with worm infestation.

PMID- 9230582
TI  - Morphological and morphometrical study of human lens in senile cataract.
AB  - Histological changes were studied in 34 senile cataractous lenses removed
      surgically from patients aged 50 to 78 years. Sixty-eight percent had nuclear
      sclerosis, 44% swollen cells and morgagnian globular changes, 23% calcium
      deposition, 15% migration of epithelial cells beneath posterior capsule and
      villous projection in posterior in 7%. Several cases had more than one
      histological abnormality. There was significant reduction in the diameter of
      epithelial cells of the cataract and insignificant change in capsular thickness.

PMID- 9230583
TI  - Guillain-Barr'e syndrome.

PMID- 9230584
TI  - Acute spontaneous spinal epidural hematoma--a life-threatening emergency.

PMID- 9230585
TI  - Shigella septicaemia in an infant.

PMID- 9230586
TI  - Claude Shannon and communication theory.

PMID- 9230587
TI  - Effects of gender on the doctor-patient relationship.
AB  - The sociopolitical changes that have occurred during the past 30 years include
      profound changes in the gender roles of men and women. As clinicians we must
      strive to be attuned to the whole spectrum of issues in our patients and in
      ourselves. We must take note of the affective climate, using our own feelings as
      the barometer, as we strive to make meaning of our patients' experiences.

PMID- 9230588
TI  - It's time for intranets.

PMID- 9230589
TI  - Ensuring access to online health information and telemedicine.

PMID- 9230590
TI  - Implications of java technology.

PMID- 9230591
TI  - HIV risk assessment: a video doctor seeks patient disclosure.
AB  - We assessed the influence of a "video doctor's" affective communication style
      (warm vs. neutral) and of a preamble to questions about sexual activity on
      patients' disclosure of risky sexual behavior and injectable drug use. To isolate
      the effects of the independent variables, we created an interactive multimedia
      program for HIV risk assessment using a video doctor portrayed by an actor.
      Participants were assigned to one of four conditions: no preamble and a neutral
      physician, no preamble and a warm physician, a preamble and a neutral physician,
      or a preamble and a warm physician. Almost 60% of a convenience sample of 393
      subjects reported engaging in two or more risky behaviors. Disclosure of risky
      behaviors was not significantly affected by the preamble. A warm communication
      style elicited more disclosure than a neutral style, suggesting that physicians'
      communication style is important in determining how much sensitive information
      patients are willing to reveal.

PMID- 9230592
TI  - From minimum data to maximum impact: using clinical data to strengthen patient
      care.
AB  - Society mandates that health care be both effective and affordable. Currently,
      data about costs of care are more readily obtainable than data about quality,
      especially in relation to nursing and other nonphysician aspects of patient care.
      Assessing effectiveness of care requires standardized data aggregated in
      databases for comparisons across times, conditions, and institutions. Historical
      and contemporary efforts to identify elements of a minimum data set and develop
      standards have brought progress but have not resolved all the critical issues. A
      project involving the University Hospital Consortium and its member institutions
      has produced a valid and reliable set of standard terms and codes compatible with
      an existing patient-level database. Future developments need to include better
      methods for determining resource consumption and for capturing clinical data. The
      time is near when databases built from clinical data will lead to knowledge that
      will strengthen patient care.

PMID- 9230593
TI  - EndNote Plus 2.2, including an add-in for Microsoft Word.

PMID- 9230594
TI  - The mathematical theory of communication. 1963.

PMID- 9230595
TI  - Stroke in young.

PMID- 9230596
TI  - Biomedical research funding in India.

PMID- 9230597
TI  - Ischaemic stroke in the young adult: clinical features, risk factors and outcome.
AB  - BACKGROUND: Stroke is an important cause of morbidity and mortality in young
      adults, especially in developing countries. This study aimed to evaluate the
      clinical features, risk factors and outcome of ischaemic stroke in young adults
      aged 15-45 years. METHODS: A retrospective review was done of the medical records
      of 177 patients seen in a tertiary referral centre in Thiruvananthapuram, Kerala
      between January 1988 and March 1994. RESULTS: There were 135 males and 42 females
      with a mean (SD) age of 34.7 (8) years at onset of stroke. An aetiological
      categorization of stroke was obtained in 111 (63%) patients and it was uncertain
      or unknown in the rest. Athero-thrombotic stroke and cardio-embolic stroke
      occurred in 24% and 17%, respectively. Hypertension, smoking, hyperlipidaemia and
      athero-thrombotic stroke were significantly more prevalent in the 31-45 year age
      group compared to the 15-30 year age group. There was only one patient with
      postpartum intracranial sinovenous thrombosis. At a mean follow up of 7 months
      (range 1-62 months), 75% of the patients were independent or only mildly
      disabled. The case-fatality rate was 1%. CONCLUSION: Ischaemic stroke in the
      young adult is more frequent in males. The aetiopathogenesis can be determined in
      the majority and the athero-thrombotic process predominates. The mortality is
      negligible and the functional outcome is good in most patients.

PMID- 9230599
TI  - Response to purified chick embryo cell rabies vaccine administered intradermally
      for post-exposure prophylaxis.
AB  - BACKGROUND: Post-exposure immunization of rabies with presently available cell
      culture vaccines in the regular five-dose intramuscular schedule is expensive for
      developing countries. In view of the latest World Health Organization
      recommendation on the use of the abbreviated intradermal regimen (now routinely
      followed in Thailand), we evaluated this regimen for the purified chick embryo
      cell vaccine. METHODS: Twenty-five subjects who had nursed or casually handled a
      rabies patient were administered purified chick embryo cell vaccine. RESULTS:
      There was 100% seroconversion and all the subjects developed neutralizing
      antibody levels higher than the adequate level of 0.5 i.u./ml. Only minor side
      effects were observed in some subjects. CONCLUSION: The feasibility of using this
      regimen in routine practice needs to be evaluated further.

PMID- 9230598
TI  - Prevalence of iodine deficiency disorders among school children of Delhi.
AB  - BACKGROUND: Iodine deficiency disorders (IDDs) are an important cause of mental
      handicap and poor educability of children. Though Delhi does not lie in the
      classical Himalayan goitre belt, it has been shown that IDD was endemic in Delhi.
      Studies of school children in Delhi reported a total goitre rate of 55% which
      indicates severe endemicity. The sale of uniodized salt has been banned in Delhi
      since July 1989. This study was done five years later to assess the impact of
      this measure on IDD prevalence in Delhi. METHODS: A cross-sectional study was
      done among class VI students studying in government schools of Delhi. A complete
      list of government middle schools in Delhi was obtained and 30 were selected on
      the basis of 'probability proportion to size'. A sample size of 1200 was decided
      based on an expected prevalence of 50% with 5% error and design effect of three.
      All children in class VI of each school were clinically examined by a trained
      doctor for the presence of goitre and casual urine samples were collected in
      capped plastic tubes. The urinary iodine estimation was done by the wet ashing
      method. RESULTS: The total goitre rate was 20.5%. If the results were limited to
      children in the age group of 10-12 years it was 19.7%. The urinary iodine was
      less than the recommended 100 micrograms/L of urine in 23.6% of the children;
      7.6% had no iodine in the urine. It is possible that some children could have
      substituted water in place of urine. The median urinary iodine level was 198
      micrograms/L of urine. CONCLUSION: The study showed that IDD continues to be
      prevalent in mild endemic proportions. Compared to the results of previous
      surveys, the IDD rates have declined in the last few years. However, it continues
      to be an important public health problem in Delhi. It is essential to monitor the
      iodine content of salt on a regular basis. IDD control activities should be
      strengthened in Delhi and repeat surveys should be done every 3-5 years to
      monitor the progress achieved in eliminating IDD.

PMID- 9230600
TI  - Aetiology of hyperkalaemia in hospital inpatients.
AB  - BACKGROUND: Hyperkalaemia is a common metabolic disorder; if left untreated it
      can lead to life-threatening consequences. We conducted this study to determine
      the common aetiological factors for hyperkalaemia in hospital inpatients.
      METHODS: This prospective cross-sectional study was conducted in a referral
      teaching hospital in south India. One hundred and forty-three patients with
      hyperkalaemia (> 5 mEq/L) were selected on 20 random week days over a 3-month
      period. All the patients were clinically and biochemically evaluated for the
      aetiology of hyperkalaemia. RESULTS: Hyperkalaemia was twice as common amongst
      males. Potassium supplementation and drugs were the leading causes for
      hyperkalaemia, with renal failure being a distant second. Hyperkalaemia developed
      after admission to hospital in more than 75% of the patients. Severe
      hyperkalaemia (> 6 mEq/L) was seen in one-third of the patients. CONCLUSION:
      Potassium supplementation and other iatrogenic conditions lead to hyperkalaemia
      in inpatients. Males are at increased risk for hyperkalaemia.

PMID- 9230601
TI  - Brain death and organ donation.
AB  - Brain death is the irreversible cessation of all brain functions. Brainstem death
      is the 'physiological core' of brain death. The Indian Parliament has given legal
      recognition to brain death though it applies only in the context of performance
      of organ transplantation. Brain death is diagnosed if there is irreversible loss
      of consciousness, absence of brainstem reflexes and apnoea. Care and diligence in
      the application of the criteria for brain death provide important safeguards for
      Individual patients and the community in general. These criteria also allow death
      to be diagnosed with certainty prior to the occurrence of circulatory arrest.
      Solid organ transplantation has become possible through the diagnosis of brain
      death but is not the primary consideration; the management of a potential organ
      donor, who is brain dead, is also vital. If optimal preservation of organs for
      transplantation is to be achieved the clinician needs to understand the
      pathophysiology and consequences of changes occurring in various organs after
      brain death and active management is required to reverse or control these
      changes. Discussions about organ donation with relatives of brain deed patients
      are never easy. These should always be frank and sympathetic. It has been
      suggested that those whose interests lie in transplantation must bear the
      responsibility of educating the general public. This will help intensivists who
      expose themselves knowingly to the unpleasant aspects of organ donation.

PMID- 9230602
TI  - Vaginal hysterectomy.
AB  - The authors report on their experience of vaginal hysterectomy in a prospective
      series of 14 patients with myomatous uteri of the size of 14 to 20 weeks'
      gestation. The mean uterine volume at the time of surgery was that of 16 1/2
      weeks' gestation. The largest myoma had a diameter of 11.6 cm. Five of the
      patients were also scheduled to undergo bilateral oophorectomy. The paracervical
      tissues were infiltrated with a dilute solution of lignocaine and adrenaline.
      Circumferential incision and reflection of the vaginal wall, dissection of the
      bladder cephalad, opening of the vesico-uterine fold anteriorly and the pouch of
      Douglas posteriorly were performed initially. This was followed by clamping,
      division and ligation of the sacro-uterine and cardinal ligaments and of the
      uterine vessels, as is done during a vaginal hysterectomy. The next step depended
      on the size and other features of the uterine corpus and included bisection,
      myomectomy, morcellation and coring. BISECTION: The cervix was grasped on both
      sides and the uterus was bisected sagittally towards the fundus, using a knife.
      The bisection, carried out first along the posterior uterine wall, was aided by
      the repeated repositioning of the vulsella close to the apex of the incision,
      combined with rotation of the cervical portion of the uterus around the public
      arch. If necessary, the uterus was rotated back to its original position and the
      bisection pursued anteriorly. Complete bisection often allowed half the uterus to
      be delivered through the vagina and the ovarian pedicle to be secured; the same
      was then done with the other half of the uterus. Myomectomy was frequently
      combined with bisection or morcellation. Smaller myomas were removed in one piece
      while larger ones were morcellated and removed in fragments, one of the vulsella
      always being attached to the residual bulk of the myoma. Morcellation was carried
      out on the uterus when despite bisection or myomectomy no further descent was
      possible. Bisection was recommenced as soon as further descent of the uterus
      could be achieved after myomectomy and morcellation. Coring was performed instead
      of bisection when dealing with smaller uteri without any distinct large myoma. A
      circumferential incision was made at the level of the uterine isthmus about 5 mm
      into the substance of the corpus. A central core of tissue around the uterine
      cavity was then excised by progressively undercutting the serosal surface of the
      uterus towards the fundus. Once the uterus was delivered into the vagina, the
      hysterectomy was completed in the usual fashion. All 14 procedures with or
      without oophorectomy or salpingo-oophorectomy were completed successfully. The
      mean weight of the uteri was 639 g (range 380-1100 g), the mean operating time
      was 84 minutes (range 30-150 minutes) and the mean operative blood loss was
      estimated at 296 ml (range 100-800 ml). One patient was given a blood transfusion
      immediately postoperatively. Six women had macroscopic haematuria that cleared up
      within 24 hours. There were no other important complications. Postoperative
      hospital stay averaged 3.7 days (range 2-9 days). Only 2 patients remained in
      hospital for more than 4 days after surgery. All women had recovered fully by the
      time of their follow up appointment.

PMID- 9230603
TI  - Immune response to beta casein in insulin-dependent diabetes mellitus.

PMID- 9230604
TI  - Setback to immunotherapy strategies of breast cancer.

PMID- 9230605
TI  - Conjunctivitis and red eye.

PMID- 9230606
TI  - Reproductive health in India's primary health care system.

PMID- 9230607
TI  - Defining hypertension in the Indian population.

PMID- 9230608
TI  - Problems of patients testing positive for HIV.

PMID- 9230609
TI  - The Wishaw E. coli O157:H7 outbreak.

PMID- 9230610
TI  - 'Integrated' medical care combines allopathic and alternative treatments.

PMID- 9230612
TI  - Generic prescription and anti-amoebic drugs.

PMID- 9230611
TI  - Dr B.S. Narang memorial symposium: biochemistry in medical education-1, molecular
      biology in undergraduate teaching, New Delhi, 16 November 1996.

PMID- 9230613
TI  - A partogram to reduce maternal and infant morbidity and mortality.

PMID- 9230614
TI  - Bone marrow transplantation from unrelated volunteer donors. An overview.
AB  - Marrow transplantation from a phenotypically identical unrelated donor has become
      a feasible and curative form of treatment for patients with several malignant and
      nonmalignant disorders who lack an HLA-matched sibling donor. Given the rapid
      growth of registries of HLA-typed volunteers-including nearly 3,000,000 people-it
      is now possible to identify a suitable unrelated marrow donor for up to 50% of
      patients. In this review the recent acquisitions regarding the structure of HLA
      complex, the new molecular typing technologies and clinical results obtained with
      unrelated marrow transplants, will be considered.

PMID- 9230615
TI  - The reliability of evoked spinal cord potentials elicited by direct stimulation
      of the cord as a monitor of spinal cord ischemia during temporary occlusion of
      the thoracic aorta.
AB  - Paraplegia is a severe and disastrous complication of operations on the thoracic
      aorta. For preventing this complication, we employed evoked spinal cord
      potentials elicited by direct stimulation of the cord (ESPs-dsc) during
      operations on 83 patients with various aortic lesions (37 dissecting and 46 cases
      of nondissecting aneurysms, 35 descending and 48 thoracoabdominal aortic
      aneurysms). All of the patients had some form of circulatory adjunct during
      aortic cross-clamping. Of the 83 patients, three had "immediate" paraparesis and
      five had "immediate" paraplegia, whereas three other patients had "delayed"
      paraplegia. During operation, four types of ESPs-dsc response pattern were
      observed: (1) no change (n = 57), (2) change with return (n = 15), (3) change
      with inconsistent return (n = 6), (4) change without return (n = 5). "Delayed"
      paraplegia occurred in two patients with "no change" and "change with return"
      response (3%), "immediate" paralysis occurred in three and "delayed" paraplegia
      occurred in one of those with "change with inconsistent return" response (67%),
      and all of those with "change with inconsistent return" response (67%), and all
      of those with "change without return" response developed "immediate" paraplegia
      (100%). We conclude that intraoperative monitoring of spinal cord function
      utilizing ESPs-dsc is a good indicator of spinal cord ischemia and we can improve
      the outcome according to its changes.

PMID- 9230616
TI  - The involvement of immune reactions in cardiac damage during acute myocardial
      infarction: role of cell-mediated immune response.
AB  - This study was undertaken with the aim of investigating humoral and cell-mediated
      immune response in acute myocardial infarction (AMI) as possible mechanisms
      involved in the infarction enlargement. Twenty three patients with first AMI and
      15 healthy volunteers were examined. Of the AMI patients, 14 had extensive
      infarction (group A), while 9 patients had small infarction (group B).
      Immunologic analyses were performed at admission, and repeated after 3, 7, 14 and
      21 days of the acute event. Following parameters were tested: number of CD3+,
      CD4+, CD8+ and CD20+ cells; serum IgG, IgA, IgM, C3, C4, immune complex and
      anticardiac antibody levels; polymorphonuclear cell (PMN) function (chemotaxis,
      phagocytosis, metabolic activity); leukocyte migration in vitro in the presence
      of water-soluble homologous heart extract. It was demonstrated that the number of
      B cells, serum IgG, C3, immune complex and anticardiac antibody levels were
      elevated from 7th-14th days after AMI. Concerning these parameters, however, no
      significant differences were obtained between group A and group B of AMI
      patients. Chemotaxis and metabolic activity of peripheral blood PMN, but not
      phagocytosis, were enhanced during AMI, again changes of PMN did not correlate
      with the extension of infarction. In contrast, leukocyte migration inhibition in
      vitro revealed that only patients with extensive AMI have developed positive
      reaction during the first 14 days after the onset of the disease, while leukocyte
      inhibition reaction appeared in patients with nonextensive AMI not earlier than
      the 21st day after the infarction. These findings demonstrate generation of
      immune reactivity during AMI and indicate that humoral immune response seems more
      likely to be an epiphenomenon related to tissue necrosis, while cell-mediated
      immune reactions could influence the extensiveness of cardiac damage.

PMID- 9230617
TI  - Influence of twist on vein and PTFE graft hemodynamics: an ex vivo experimental
      study.
AB  - OBJECTIVE: In an ex vivo infusion model, the effect of different factors
      affecting the critical level of twist in vein and PTFE grafts was analysed.
      SETTING: University Hospital, Department of Surgery. EXPERIMENTAL DESIGN: Saline
      perfusion of grafts with various diameter and length under constant high (90
      ml/min) and low (50 ml/min) flow rates against various peripheral resistance was
      performed. MEASURES: The pressure changes in the grafts were measured at
      increasing increments of twisting. RESULTS: The critical level of twist appears
      to be dependent on the diameter, length, stretching, status of peripheral
      resistance, amount of volume flow and the type of graft material, varying between
      90 to more than 360 degrees. In vein grafts critical twisting appeared earlier
      with a decrease in diameter, shortening in length, high peripheral resistance,
      high flow rate and stretching. PTFE grafts especially with external spiral
      support were resistant to twist. CONCLUSIONS: These data suggest that the
      critical level of graft twist is dependent upon multiple factors and moderate or
      even high grade twist with especially externally supported PTFE grafts regardless
      of length and long mobilized vein grafts do not lead to hemodynamic changes. On
      the other hand total cessation of flow occurs at lower degrees of twist in
      stretched, short vein grafts.

PMID- 9230618
TI  - Haemostatic parameters in patients with primitive venous hypertension.
AB  - In twenty patients with primitive venous hypertension and in ten healthy subjects
      we have determined the plasmatic levels of: Thrombomodulin (TM), beta
      Thromboglobulin (beta-TG), D-Dimer (DD), the tissue activator of the plasminogen
      (t-PA) and the inhibitor of the activator of the plasminogen (PAI-1). The levels
      of the parameter we studied have shown in the patients a significant difference
      of beta-TG (p < 0.01) and PAI-1 (p < 0.01) compared to the controls, whereas
      there was no significant difference in the other parameters we studied. Our data
      underline, in patients with primitive venous hypertension, the importance that
      the activation of the platelets and the reduction of the potential fibrinolytic
      can assume, together with the stasis, regarding the onset of thrombotic
      complications.

PMID- 9230619
TI  - Long-term prevention of atrial fibrillation after coronary artery surgery.
AB  - We researched the necessity of quinidine fumarate or acebutolol prophylaxis in
      patients in whom atrial fibrillation occurred in the postdischarge period and
      returned to sinus rhythm after coronary artery surgery. DESIGN: Prospective
      review. PATIENTS: Since 1992, 60 patients were chosen in whom atrial fibrillation
      occurred in early postoperative period. There were no significant differences
      between them and they were separated into 3 groups. In group I (20 patients) we
      did not give any drug, in group II (20 patients) quinidine fumarate was given and
      in group III (20 patients) acebutolol was given and patients were controlled for
      90 days. RESULT: Atrial fibrillation occurred in one patient in group I, (5%),
      two in group II (10%) and two in group III (10%), (p < 0.05). Different from the
      other groups, atrial fibrillation was asymptomatic with low ventricular response
      in group III. CONCLUSIONS: There were no significant differences among three
      groups statistically, so we suggested that long-term prevention of atrial
      fibrillation with quinidine fumarate or acebutolol was not necessary after
      coronary artery surgery.

PMID- 9230621
TI  - Physics in medicine: a potential unfolding in the radiological sciences.
AB  - Advances in civilization often depend upon a vision which reduces the complex to
      the simple, and fundamental. This paper presents an essential, reductionist
      understanding of biosystems in terms of electrogravitational circuits. This
      conceptualization yields innumerable ideological appendages one of which is
      Jacobson Resonance, a general mechanism explaining electromagnetic field
      bioeffects. Biological amplification of hyperfine, ultrafine and dipole-dipole
      interactions, biological time dilation, molecular vibrational frequencies and
      biophotonic-phonon transductions are explained in detail. In this paper, Jacobson
      theory gives the reader food for epistemological thought, viewing biological
      matter in terms of general physical principles, which yield a fresh insight for
      solving a diverse array of health problems.

PMID- 9230620
TI  - Reliability of ultrasounds in detecting common bile duct stones before biliary
      surgery. A retrospective analysis.
AB  - The aim of this study is to evaluate the diagnostic benefit of US in the
      preoperative screening for CBD stones in patients submitted to surgery for
      biliary lithiasis. MATERIALS AND METHODS: We analyzed the data of 135 patients
      admitted for biliary lithiasis, jaundice or biliary pancreatitis in the last
      three years. Mean age was 63 years (54.8% females), 48% of the cases had an
      urgent admission. US of the liver and biliary ducts was the first examination
      performed and the patients were divided in 2 groups on the bases of the results:
      those with the diameter of the CBD < 1 cm (101 pts-group A) and those with a
      diameter > 1 cm (34 pts-group B). RESULTS: In group A were subsequently
      performed: 35 IV cholangiographies (6 showed CBD stones, 1 was a false negative
      for CBD stones), 15 intraoperative (I.O.) cholangiographies (1 positive for CBD
      stones), 9 ERCP for jaundice or pancreatitis (2 positive for CBD stones). The
      incidence of CBD stones was 8.9% in this group. In group B were performed: 7 IV
      cholangiographies (2 showed CBD stones), 12 I.O. cholangiographies (6 showed CBD
      stones), 10 ERCP for jaundice or pancreatitis (7 showed CBD stones). The
      incidence of CBD stones was 44% in this group. CBD stones were detected by US in
      2 cases (22%) in group A and in 6 cases (40%) in group B. CONCLUSIONS: In our
      patients there is a relatively high incidence of CBD stones (8.9%) in spite of a
      normal CBD at US. Considering that the minimally invasive approach for the
      gallbladder stones is becoming the "gold standard" and the laparoscopic treatment
      of the CBD stones is not widely diffused, it is important to know the presence of
      CBD stones before surgery. With this in mind US does not seem to be a reliable
      diagnostic tool and we suggest that before surgery an IV cholangiography
      (sensitivity > 95% in our experience) should be performed together with US and
      ERCP in selected cases. Moreover this could reduce the number of preoperative
      ERCP leaving the possibility to treat more selectively by endoscopic
      papillosphincterotomy the patients with CBD stones before laparoscopic
      cholecystectomy.

PMID- 9230622
TI  - Successful non operative management of late infrainguinal polytetrafluoroethylene
      vascular graft infection with antibiotics alone: a report of two cases.
AB  - Polytetrafluoroethylene (PTFE) prosthetic vascular graft infection is a serious
      complication of arterial reconstructive surgery. Traditional management is
      primarily surgical and may result in long hospital stay with significant
      morbidity and mortality. The authors describe two cases of infected
      femoropoliteal PTFE grafts which were managed non operatively with antibiotic
      therapy alone, resulting in early return to normal activities and excellent
      resolution of infection on Indium labelled leucocyte scanning. The authors
      suggest that in selected cases antibiotic therapy alone is a valuable tool in the
      management of infrainguinal PTFE prosthetic sepsis.

PMID- 9230623
TI  - Extension of the Taylor patch concept to infrainguinal sequential arterial
      bypass.
AB  - Infra-inguinal bypass to popliteal and tibial vessels for limb salvage is a well
      established procedure with excellent results when saphenous vein is used as a
      conduit for the bypass. Infra-popliteal bypass, using a prosthetic conduit, is
      generally accompanied by poor results Taylor et al. recently obtained impressive
      results using PTFE as a conduit and a vein patch at the distal anastomosis.
      Extension of the Taylor patch concept to infrainguinal sequential arterial bypass
      in case report form is presented.

PMID- 9230624
TI  - Urgent coronary artery revascularization with different arteries.
AB  - Authors present the case report of a young man with advanced coronary artery
      disease of the left main trunk, and the large tributaries of the left coronary
      system, leading to sudden onset of many ventricular fibrillation, associated with
      unconsciousness requiring several reanimation. The condition was treated with
      coronary artery surgery with the use of three different arterial conduits (right
      radial artery, right gastroepiploic artery as free grafts and the left internal
      mammary artery in situ) with an additional saphenous vein bypass graft. Details
      of surgical activity as well as the documents of the early postoperative course
      and of the 1 month follow-up are described.

PMID- 9230625
TI  - Simultaneous ileal intussusception and volvulus after jejunoileal bypass for
      morbid obesity.
AB  - OBJECTIVE: The aim of this work is to consider the mechanical complications of
      jejunoileal bypass for morbid obesity which can have a serious outcome because of
      the occult nature of the symptoms. DESIGN: The mechanical complications of
      jejunoileal bypass are mainly intussusception of the bypassed ileal segment,
      internal herniation of the ileal loops through the mesenteric defects and
      laparocele. SETTING AND PATIENTS: A recent case is reported in which, most
      unusually, intussusception and volvulus were both present, with ischaemia and
      necrosis of the bypassed segment. Moreover, the general health of the patient
      remains normal despite the severity of the complication. MAIN OUTCOME MEASURES:
      Examination of blind loop with CT scan which showed an abdominal mass of
      uncertain interpretation. INTERVENTION: A laparotomy revealed a volvulus of
      bypassed ileal loops, probably caused by a simultaneous ileal intussusception and
      an adhesion. On account of the extensive nature of the process and the degree of
      advanced ischaemia and gangrene patches in the folds of the ileum, resection of
      the entire bypassed segment as far as the previous jejunoileal anastomosis was
      necessary. CONCLUSION: The authors point out the occult nature of the
      manifestations of this type of complication: aspecific abdominal pains in all
      quadrants, fever, non vomiting, normal passing of faeces and gas and suggested
      that simultaneous diverticulitis of the colon (frequently found in the obese) can
      further complicate and delay diagnosis.

PMID- 9230626
TI  - The use of bifurcated and not reversed saphenous vein. Report of two cases.
AB  - BACKGROUND: This study was designed to determine the use of bifurcated and not
      reversed saphenous vein in different cases. CASE DESCRIPTION: We report two cases
      treated in the department of vascular surgery (Busto Arsizio, Varese, Italy) in
      which different arterial tracts had to be revascularized at the same time using
      not reversed autologus greater bifurcated saphenous vein. They are two different
      clinical situations (infection and very distal revascularization) treated by the
      same surgical technique. The two patients were subjected to angiographic
      examination in the pre- and postoperative period. During their follow-up, we
      carried out noninvasive surveillance (Doppler c.w.). The second were also
      subjected to bacterial culture and antibiogram to establish an adequate
      antibiotic therapy. The mean follow-up was 22 months: during this period rest
      pain disappeared and the trophic lesion recovered. CONCLUSIONS: In our
      experience, the use of not reversed and bifurcated vein was haemodynamically
      valid and able to maintain an arterial blood flow on the receiving arteries.

PMID- 9230627
TI  - Suggested new operative approach in the treatment of Lutembacher's syndrome, with
      moderately hypoplastic left ventricle.
AB  - Lutembacher's syndrome or ASD secondum and rheumatic mitral stenosis is treated
      with surgery but in some instances of presence of small left ventricle surgery
      will lead to death. Nazem's approach which is our Staged Suggested Method has
      saved several patients with this kind of pathology.

PMID- 9230628
TI  - Use of the Oximeter-539 WTW, equipped with a sensor Trioxmatic-300, for the
      functional analysis of dilute solutions of human Hb-A.
AB  - Dissociation curves for oxygen of dilute samples of human adult Hb-A were
      evaluated on this occasion, by using the Oximeter-539 WTW with its sensor, and a
      suitable spectrophotometer. At this purpose, Hb samples were desaturated in
      oxygen upon given experimental conditions, by bubbling pure nitrogen in them, and
      their re-oxigenation in air was followed, step by step, by multiple oximetries.
      In addition, all the spectrophotometric measurements of the saturation of Hb-O2%,
      corresponding to each individual oximetry, were carried out parallely but
      separately. Dilution of Hb-A was maintained at 0.1 mM in heme. The p50 at pH 7.3
      was 4.435 +/- 0.299 Torr, with the n-value of 2.7 +/- 0.2; Bohr effect was -0.55
      +/- 0.08, within a pH range between 6.8, 7.3 and 7.8, whereas chloride and DPG
      effects at pH 7.3 (the most useful value) were 0.42 +/- 0.44 and 0.453 +/- 0.0187
      respectively. In conclusion, these results are similar to those obtained with
      automated procedures, upon comparable experimental conditions, but do not require
      expensive and sophisticated instruments. Such a technique could be very useful in
      the hemoglobinopathies, which are common in Italy, and it could be easily adapted
      to perform comparative studies on animal hemoglobins not far from human species.

PMID- 9230629
TI  - NIH: gearing up for the twenty-first century.

PMID- 9230630
TI  - Persistent changes in corticotropin-releasing factor systems due to early life
      stress: relationship to the pathophysiology of major depression and post
      traumatic stress disorder.
AB  - In addition to a genetic contribution to the vulnerability for mood and anxiety
      disorders, such as major depressive disorder (MDD) and post-traumatic stress
      disorder (PTSD), a preeminent role of early adverse life events in the
      pathogenesis of these disorders has been postulated. Corticotropin releasing
      factor (CRF), which has been conclusively documented to be the major regulator of
      the mammalian stress response, may be the seminal neurobiological substrate
      mediating the effects of early life stress on subsequent psychopathology. Central
      administration of CRF produces many of the physiological and behavioral effects
      of stress and of anxiety and depression. Clinical studies have provided evidence
      for increased activation of CRF neuronal systems in both MDD and PTSD. Similar
      hyperactivity of CRF neurons and sensitization of the pituitary-adrenal stress
      response has been observed in adult animals exposed to stress early in life. We
      propose that early adverse life events might render the human individual
      vulnerable to the effects of stress later in life, resulting in an increased risk
      for developing psychopathology via long-lived alterations in CRF-containing
      neural circuits. Based on these findings, new therapies including early
      intervention can now be developed to treat individuals exposed to severe stress
      early in life.

PMID- 9230631
TI  - A view on noradrenergic, hypothalamic-pituitary-adrenal axis and
      extrahypothalamic corticotrophin-releasing factor function in anxiety and
      affective disorders: the reduced growth hormone response to clonidine.

PMID- 9230632
TI  - The thyroid axis and mood disorders: overview and future prospects.
AB  - For over 200 years, the relationships between neuroendocrine systems and mental
      illness have been studied. Research has focused in substantial part on mood
      disorders and thyroid axis function. This review presents a brief examination of
      the history and the progress in this area of investigation. Consideration is
      given to mood states in thyroid disorders, as well as to thyroid function in mood
      disorders. Thyroid hormones, usually in conjunction with standard medications,
      can be used to treat both manic and depressed phases of mood disorders. The
      review with a presentation of some of the many issues that merit further
      investigation.

PMID- 9230633
TI  - Neuroregulatory role of gonadal steroids in humans.

PMID- 9230634
TI  - Gender, estrogen, and schizophrenia.
AB  - Most of the evidence to support an association between estrogen and psychosis is
      indirect and comes from clinical studies of gender differences in schizophrenia
      and from studies of fluctuating levels of psychopathology in different phases of
      the menstrual cycle. Our data, as well as those of other investigators, suggest a
      significantly later age at onset of schizophrenia in women than in men. There is
      somewhat more direct evidence from animal studies indicating that estrogen
      modulates dopamine systems in a manner similar to neuroleptics, although there
      are some inconsistencies in the literature. Few studies have examined the effects
      of estrogen administration in conjunction with neuroleptics on psychotic
      symptoms. We present a case report of a postmenopausal women with schizophrenia
      who had an improvement in positive symptoms with estrogen replacement therapy.
      Long-term double-blind treatment studies are needed to investigate the effects of
      estrogen on psychotic symptoms in women with schizophrenia.

PMID- 9230635
TI  - The influence of estrogen on monoamine oxidase activity.
AB  - The enzyme monoamine oxidase (MAO) has generated considerable interest as a
      biological marker. The serendipitous discovery that iproniazid was a weak MAO
      inhibitor (MAOI) led to the development and widespread use of MAOIs as
      antidepressants in the early 1950s. The-discovery of the two isoenzymes of MAO
      has led to the development of selective MAOIs that may have a more favorable side
      effect profile. The regulation of MAO is multifactorial, and there is evidence
      that it involves estrogens. Improvement in mood and cognition reported in women
      on estrogen replacement therapy may also involve changes in MAO activity. The
      literature in this regard is reviewed here, and possible implications of the
      effects of estrogens on MAO activity are discussed.

PMID- 9230636
TI  - Gender differences in psychotropic drug metabolism.

PMID- 9230638
TI  - Nortriptyline and its hydroxymetabolites in breastfeeding mothers and newborns.
AB  - We previously reported the serum nortriptyline levels of a series of
      breastfeeding mother-infant pairs. Nortriptyline was below the level of
      detectability in the infants' sera; however, two young infants aged 10 weeks or
      less had low concentrations of 10-hydroxy-nortriptyline. Because very young
      breastfeeding infants are likely to be at increased risk for toxicity, we have
      focused our study on breastfeeding newborns. We present additional data from six
      mothers and their infants (4 weeks of age), as well as data from one prematurely
      born baby. We were able to quantify nortriptyline in one infant and another had
      higher levels of hydroxymetabolites than previously reported, although still very
      low. No adverse clinical effects were observed in the infants.

PMID- 9230637
TI  - Effects of the postpartum period on nortriptyline pharmacokinetics.
AB  - The objective of this research was to investigate sequential serum levels and
      level/dose ratios of the tricyclic antidepressant nortriptyline (NTP) through the
      first 17 postpartum weeks. The initial NTP dose was given immediately postpartum
      to 16 mothers and increased gradually to 70 mg over the first week. A dose of 75
      mg was prescribed until adjustment according to serum levels. Serum levels of NTP
      and its metabolites Z- and E-OH-NTP were determined. At postpartum Week 2, the
      women developed a mean level/dose (L/D) ratio for NTP of 1.11 (range 0.37 to
      3.23), and subsequently experienced an increase in the L/D ratios which continued
      through Week 6. At Week 8, the NTP L/D ratios declined, and became relatively
      stable at Week 11 and beyond. For postpartum women treated with NTP, side effect
      profiles should be carefully followed during the first 6 weeks after delivery as
      a clinical marker for elevation of serum levels. Since our highest L/D ratios for
      NTP occurred at Week 6, a serum level is recommended at this time. If the dose
      needs to be lowered to maintain a nontoxic level, a repeat serum level should be
      obtained at Week 11, at which time an increase in dose may be required.

PMID- 9230640
TI  - Sertraline in coexisting major depression and diabetes mellitus.
AB  - As many as 25 percent of patients with diabetes mellitus may also have depressive
      symptoms. Tricyclic antidepressants (TCAs) may produce increased appetite and
      weight gain with adverse consequences for diabetes. The selective serotonin
      reuptake inhibitors (SSRIs), however, may improve fasting blood sugar in
      laboratory studies. In an initial application, sertraline was administered at a
      dose of 50 mg/day in a 10-week open study to 28 non-insulin-dependent diabetes
      mellitus (NIDDM) patients with DSM-III-R major depression after a 2-week single
      blind placebo washout period with a minimum 17-Item Hamilton Rating Scale for
      Depression (HAM-D) score of 18. The patient group included 16 males and 12
      females with a mean age of 54.2 +/- 8.8 years. Results indicated (1) significant
      improvement in mean HAM-D (22.6 +/- 3.4 to 4.9 +/- 5.9, p < .001) and in mean
      Beck Depression Inventory (BDI) scores (21.9 +/- 10.5 to 12.7 +/- 8.3, p < .001);
      (2) fall in platelet serotonin (5-HT) content (79.7 +/- 22.5 to 13.6 +/- 12.7
      ng/10(8) platelets, p < .001); (3) correlation of baseline platelet 5-HT content
      with response to sertraline by BDI scores (r = 0.51, p < .05); (4) improved
      dietary compliance for those with baseline value below 70 percent (59.7% to
      69.1%, p < .005); and (5) 13 of 17 patients with baseline glycosylated hemoglobin
      A (HbA1c) levels greater than 8.0, showed a reduction (p = .018). Sertraline may
      be an effective antidepressant in patients with diabetes mellitus and response
      may be predictable by higher baseline platelet 5-HT content, with the potential
      to improve dietary compliance and reduce HbA1c measures. As with all open
      studies, replication is essential.

PMID- 9230639
TI  - Acute alpha 2 blockade by idazoxan increases insulin and lowers plasma glucose
      during positron emission tomography.
AB  - The sympathetic nervous system can modulate glucose levels through a variety of
      mechanisms, including inhibition of insulin release by alpha2-adrenergic
      receptors. Such effects could potentially confound measurements of brain glucose
      metabolism during studies of the central actions of sympathomimetic drugs. Plasma
      glucose, insulin, and sympathetic responses to alpha2 blockade were measured
      following infusion of idazoxan, a selective alpha2 antagonist, or placebo, in 33
      healthy volunteers (idazoxan: n = 23, placebo: n = 10). These measures were
      compared with estimates of global brain metabolism obtained from positron
      emission tomography (PET) scans before and after the infusion. Glucose levels
      fell and fractional levels of insulin rose after idazoxan, compared with placebo.
      Relative increases in insulin correlated with increases in epinephrine after
      active drug. The increases in insulin are consistent with the hypothesized role
      of alpha2-adrenoceptors in regulating insulin release. Estimates of global brain
      glucose metabolism did not appear to be influenced by the modest changes in
      plasma glucose.

PMID- 9230641
TI  - Neuroendocrine effects of electroconvulsive therapy (ECT).
AB  - Reliable observation of ECT-induced hormone release requires that other processes
      that affect hormone levels remain constant and not obscure it. This article
      reviews principles and pitfalls in making such observations. Clinical
      applicability and limitations of measurements of prolactin, cortisol, oxytocin,
      vasopressin, and other hormones are described. Applications include elucidation
      of ECT physiology and seizure quality, comparison of ECT techniques, and
      description of illness severity. Accounting for each of these different effects
      can be needed to characterize any of them. An important but unrealized
      application of neuroendocrine measurement is prediction of the stability of
      individual ECT response.

PMID- 9230642
TI  - Use of thyroid hormone to diminish the cognitive side effects of psychiatric
      treatment.
AB  - Electroconvulsive therapy (ECT) and lithium are highly effective treatments for
      mood disorders. Both treatments, however, are associated with cognitive side
      effects which reduce patient compliance and treatment satisfaction. Both
      therapies also have a significant effect on hypothalamic-pituitary-thyroid axis
      (HPT) activity. Preliminary results from a double-blind, placebo-controlled study
      of adjunctive thyroid hormone (T3) and ECT showed better memory function in
      patients receiving T3 compared with placebo. This neuroprotective effect of T3
      has been confirmed using electroconvulsive shock (ECS) in rats, and shown to be
      independent of the number of electrical stimulations. Results of studies in
      patients with bipolar disorder taking lithium have demonstrated that cognitive
      deficits are significantly related to diminished thyroid status, but not lithium
      levels. Preliminary evidence also shows that adjunctive thyroid hormone improves
      cognitive functioning in patients taking lithium. These findings, if replicated
      and confirmed, indicate a potential role for adjunctive thyroid hormone in
      reducing the cognitive side effects of these important psychiatric treatments.
      This, in turn, may lead to improved treatment compliance, diminished overall
      morbidity, and reduced healthcare utilization.

PMID- 9230643
TI  - Hormonal interventions with psychopharmacological potential: an overview.
AB  - The better understanding of how hormones modulate cognition and behavior is
      associated with the application of hormones as psychotropic medications. Several
      natural and synthetic hormones are used as adjuncts to antidepressant medications
      or as treatments in their own right. We discuss pharmacotherapeutical aspects of
      estrogen, thyroid hormones, cortisol suppressors, and melatonin as examples of
      current trends in the field. In addition to the putative roles of these hormones
      in the treatment of affective disorders, estrogen might also be used as a
      cognition-enhancer, and both estrogen and thyroid hormones might have roles as
      mood stabilizers. The psychotropic effects of melatonin have recently received
      significant attention, but the exact role of that hormone still needs to be
      clarified.

PMID- 9230644
TI  - Estrogen in geriatric psychopharmacology.

PMID- 9230645
TI  - The role of estrogen in late-life depression: opportunities and barriers to
      research.

PMID- 9230646
TI  - Androgens in the elderly: will androgen replacement therapy improve mood,
      cognition, and quality of life in aging men and women.

PMID- 9230648
TI  - Gonadotropin-releasing hormone agonist in the treatment of premenstrual symptoms
      with and without ongoing dysphoria: a controlled study.
AB  - Gonadotropin-releasing hormone (GnRH) agonists have been shown to reduce symptoms
      of premenstrual syndrome (PMS). This randomized, placebo-controlled study
      examined the efficacy of the GnRH agonist, leuprolide acetate depot, in a clearly
      defined PMS sample versus women with premenstrual symptoms in combination with
      dysphoric symptoms throughout the cycle, termed the premenstrual exacerbation
      (PME) group. Evaluation included the Structured Clinical Interview for DSM-III-R,
      administered in the follicular phase, and the subject Penn Dally Symptoms Report
      (DSR) maintained throughout the study. Thirty-three eligible women were
      randomized to double-blind treatment and administered 3.75 mg of depot leuprolide
      or a placebo once a month for 3 months. The subjects were seen for efficacy
      evaluations at the end of each cycle. Outcome measures were the DSRs and the 17
      item Hamilton Depression Rating Scale (HAM-D17). The PMS leuprolide subjects
      improved significantly compared with the PMS placebo and PME leuprolide groups.
      The PME leuprolide group, who had dysphoric symptoms throughout the cycle, did
      not improve. Depression symptoms were at clinical levels premenstrually in the
      PMS and PME groups; following treatment they remitted in the PMS group but not in
      the PME leuprolide subjects. Efficacy did not occur until after several months of
      leuprolide treatment, but there was no evidence that PMS symptoms worsened with
      the onset of treatment. These results replicate the findings in our preliminary
      open-label study. Leuprolide reduced PMS symptoms to minimal levels where
      symptoms were limited to the luteal phase. Leuprolide was not effective for women
      with ongoing dysphoric symptoms, suggesting that premenstrual depression may have
      mechanisms different from those of other dysphoric mood disorders.

PMID- 9230647
TI  - Progesterone: does it affect response to drug?
AB  - This article presents an overview of the gamma-aminobutyric acid (GABA)
      benzodiazepine receptor complex (GBRC) and its in vitro modulation by THP, a
      metabolite of progesterone, as well as the results of a single-dose study of
      progesterone and triazolam in 16 post-menopausal women. The study results
      indicate that a 300 mg oral dose of progesterone administered 2.5 hours prior to
      a challenge dose of triazolam significantly increases sensitivity to triazolam:
      concentration values required for 50 percent of maximum effect (EC50) decreased
      by 20 to 32 percent after pre-treatment with progesterone. These data support the
      In vitro findings that THP enhances binding of benzodiazepines to the GBRC. The
      full clinical implications of these data, including extensions to other steroids,
      need to be explored.

PMID- 9230649
TI  - Anxiety and mood disorders associated with gonadotropin-releasing hormone agonist
      therapy.
AB  - Gonadotropin-releasing hormone (GnRH) agonists are synthetic derivatives of the
      native decapeptide produced by the hypothalamus. These agents cause a reversible
      suppression of the synthesis and release of luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) by the anterior pituitary gland. With GnRH agonist
      therapy, there is a resulting loss of endogenous ovarian gonadotropin stimulation
      and a severe hypo-estrogen state consistent with castrate levels of estrogen.
      Recently, GnRH agonists such as leuprolide and goserelin have been noted to be
      effective in treating mild to severe endometriosis. Side effects of these agents
      are consistent with the physiological effects of ovarian suppression, such as
      vasomotor instability, vaginal dryness, and headaches. However, despite some
      reports of emotional lability as an adverse effect of GnRH agonists, it appears
      that the occasional, rather severe psychiatric consequences of these agents are
      underappreciated. In this article, we present the case reports of 4 women of
      reproductive age with no prior psychiatric history who were treated with a GnRH
      agonist for endometriosis. These women developed symptoms consistent with various
      psychiatric disorders, including panic disorder and major depression with and
      without psychotic features. Three of these patients were given sertraline while
      on GnRH agonist therapy, which improved their mood and anxiety symptoms. Women
      undergoing GnRH agonist therapy may provide a model with which to investigate
      mood disorders during the perimenopausal stage of life.

PMID- 9230650
TI  - Access to health care. Part 3: Older adults.
AB  - OBJECTIVES: This report examines access to health care for older adults, 65 years
      of age and over. In the United States for 1993. Access indicators include having
      a regular source of care, place of care, main reason for no regular source of
      care, unmet health care needs, and use of clinical and preventive services.
      Sociodemographic characteristics include sex, age, race, income, health status,
      and health insurance coverage. METHODS: Data are from the 1993 Access to Care,
      Health insurance, and Year 2000 Surveys of the National Health interview Survey
      (NHIS), a continuing household survey of the civilian noninstitutionalized
      population of the United States. The sample for the Access to Care and Health
      insurance surveys contained 61,287 persons in 24,071 households. The sample for
      the Year 2000 survey was 21,028 persons. RESULTS: Persons with Medicare and
      private or Medicare and public coverage were more likely to have a regular source
      of medical care than elderly persons with Medicare only. Over 3.3 million elderly
      persons had at least one unmet need in 1993. Older adults on Medicare and public
      or Medicare only coverage were twice as likely to have unmet medical needs than
      those with Medicare and private coverage. Persons with Medicare and private
      coverage were more likely to receive immunizations than elderly persons with
      Medicare and public coverage or Medicare only. CONCLUSIONS: Although the majority
      of older adults have Medicare, this only provides a basic level of access to the
      health care system. Older adults who do not supplement Medicare with private
      coverage are at the greatest risk of having unmet health care needs.

PMID- 9230651
TI  - Access to health care. Part 1: Children.
AB  - OBJECTIVES: This report presents national estimates of access to medical care and
      unmet health care needs for children through 17 years of age by selected
      sociodemographic variables including sex, age, race and/or ethnicity, family
      income, family structure, place of residence, and health status. In addition, the
      impact of children's health insurance status on access to care is described.
      METHODS: Data from the 1993 Access to Care and Health Insurance questionnaires of
      the National Health Interview Survey (NHIS) are analyzed to examine access
      indicators. The NHIS is a continuing household survey of the civilian
      noninstitutionalized population of the United States. The sample included 16,907
      children from infants through 17 years of age from 24,071 households. RESULTS: In
      1993, over 7.3 million U.S. children had at least one unmet health care need or
      had medical care delayed because of worry about the cost of care. These health
      care needs included medical care, dental care, prescription medicine, glasses,
      and mental health care. In addition, almost 4.2 million children lacked a regular
      source of health care. Factors related to access indicators included health
      insurance, family income, race and/or ethnicity, family structure, and place of
      residence. The lack of health insurance or inability to afford care was the main
      reason given by respondents for children lacking a regular source of medical
      care. CONCLUSIONS: In the United States, millions of children do not receive
      needed health care services. Uninsured children and those in families with low
      income are at the greatest risk of having unmet health needs.

PMID- 9230652
TI  - Reducing the occupational risk of infections for the surgeon: multicentric
      national survey on more than 15,000 surgical procedures.
AB  - The objective of this study was to find the incidence of accidental exposures to
      blood and body fluids among surgeons during operations and to describe their
      dynamics. A probabilistic model was also used to predict the cumulative 30-year
      risk to the surgeon of contracting hepatitis B and C viruses (HBV, HCV) or human
      immunodeficiency virus (HIV) infection and estimate the effect of preventive
      strategies in reducing this risk. A multicentric prospective survey, based on
      self-administered questionnaires, was conducted during a period of 6 months in 39
      Italian hospitals. As accidental exposure to blood or body fluids occurred in
      9.2% of 15,375 operations. In about 2% of procedures a parenteral-type injury,
      such as actual skin puncture or eye contamination, was suffered by the operating
      surgeon. A needle-stick injury was the commonest accident, and its occurrence was
      found to vary with the phase of the procedure and its length. The current
      lifetime risk of acquiring HBV, HCV, and HIV infection in our regions was
      estimated to be as high as 42.7%, 34.8%, and 0.54%, respectively. The adoption of
      preventive strategies is expected to reduce this risk to 21% for HBV, 16.6% for
      HCV, and 0.23% for HIV infection. Active immunization of surgeons against HBV is
      strongly recommended. The case is also made for the use of a face-shield combined
      with a permanent change in our surgical practice capable of reducing the current
      high rate of parenteral injuries.

PMID- 9230653
TI  - Effects of polyglycolic acid and polypropylene meshes on postoperative adhesion
      formation in mice.
AB  - The purpose of this study was to investigate the effects of polyglycolic acid
      (PGA), an absorbable (ABS) mesh, and polypropylene (PP), a nonabsorbable (NA)
      mesh, on intestinal adhesion formation. Altogether 72 mice were divided into a
      control group of 24, an ABS mesh group of 23, and an NA mesh group of 25. All
      three groups were divided into two subgroups for evaluation of adhesion severity
      at postoperative (po) days 5 and 90. Adhesion severity was measured with adhesion
      grading and tissue hydroxyproline (OHP) levels. Adhesion degree was minimal (1)
      in all subjects on day 5. Also there was no difference in tissue OHP levels
      between three groups on day 5 (p > 0.05). Adhesion degree and tissue OHP levels
      as determinants of adhesion severity were higher in the PGA mesh group than the
      control group and the PP mesh group on day 90 (p < 0.001). There was no
      difference between the control group and the PP mesh groups (p > 0.05). Adhesion
      degree was higher on day 90 than on day 5 in the control group and the PGA mesh
      group (p < 0.05), whereas tissue OHP level was higher on day 90 than on day 5 in
      all three groups (p < 0.001). Also there was linear correlation between adhesion
      degree and tissue OHP levels (r = 0.86, p < 0.001). The study demonstrates that
      ABS PGA mesh has higher potential for adhesion formation than the NA PP mesh,
      probably related to the increased foreign body and inflammatory reactions during
      the absorption process of the mesh.

PMID- 9230654
TI  - Evaluation of enoxaparin given before and after operation to prevent venous
      thromboembolism during digestive surgery: play-the-winner designed study.
AB  - A total of 316 patients were included in a play-the-winner (PTW) designed study
      comparing the safety of enoxaparin started preoperatively versus postoperatively
      as prophylaxis against venous thromboembolism for digestive surgery. In a PTW
      designed study the treatment of any next patient depends on the outcome of the
      previous patient. If successful, the next patient receives the same treatment, if
      not, the comparative regimen is given. Excessive bleeding according to specified
      criteria, severe adverse reactions, clinically detected deep venous thrombosis
      (DVT), or pulmonary embolism (PE) were criteria for classification as "loser."
      The PTW design allocates most patients to the superior treatment. The main
      variable in PTW studies is the number of consecutive patients receiving the same
      treatment. In this study 163 patients were allocated to postoperatively started
      and 153 to preoperatively started prophylaxis with enoxaparin. The frequency of
      "winners" was found to be 82.8% and 78.4% in the post- and preoperatively treated
      groups, respectively. No significant differences were found between the groups
      with regard to frequency of "winners" or the number of consecutive patients
      before change of treatment. The percentile of survival distribution did not
      detect superiority of any group. Prophylaxis against postoperative venous
      thromboembolism for digestive surgery using enoxaparin can safely be started
      preoperatively.

PMID- 9230655
TI  - Early and late results of ascending aorta surgery: risk factors for early and
      late outcome.
AB  - This study was designed to evaluate risk factors for in-hospital mortality and
      midterm survival in patients undergoing ascending aorta surgery at a single
      institution during an 11-year period. Between 1984 and 1994 a total of 158
      patients underwent an ascending aorta procedure at our institution. Their mean
      age was 59.6 +/- 12.3; 115 (73%) were male, 33 (21%) had a history of congestive
      heart failure, 61 (39%) had an acute type A dissection, 21 (13%) underwent redo
      operations, and 55 (35%) were operated on an emergency basis. In-hospital
      mortality was 9.7% (10/103) for elective procedures and 36.4% (20/55) for
      emergency operations (p < 0.0001). Multivariable stepwise logistic regression
      analysis identified the cardiopulmonary bypass time [odds ratio (OR) = 1.01/min,
      p = 0.0021], emergency operation (OR = 2.27, p = 0.0022), arch replacement (OR =
      2.71, p = 0.0067), and the need of femoral vein cannulation at intervention (OR =
      1.89, p = 0.0375) as independent predictors of in-hospital death. When this kind
      of analysis was performed, evaluating only the variables known before surgery,
      acute type A dissection (OR = 2.21, p = 0.0009) and preoperative NYHA class (OR =
      1.88 per class, p = 0.0290) were independent risk factors for in-hospital death.
      Follow-up ranged from 10 to 126 months (median 42 months), with Kaplan-Meier
      survivals of 69 +/- 4%, and 60 +/- 5% at 5 and 7 years, respectively; survival
      rates for hospital survivors were 85 +/- 4% and 67 +/- 7% at 5 and 7 years,
      respectively. Cox regression analysis has identified arch replacement [relative
      risk (RR) = 2.48, p < 0.0001], perioperative myocardial infarction (RR = 2.44, p
      = 0.0003), preoperative NYHA class (RR = 1.97 per class, p = 0.0009), acute type
      A aortic dissection (RR = 1.44, p = 0.0238), the need of femoral vein cannulation
      at intervention (RR = 1.55, p = 0.0332), and redo operation (RR = 1.44, p =
      0.0851) as independent predictors of reduced survival at follow-up. When this
      kind of analysis was performed on hospital survivors only, postoperative
      tracheostomy (p = 0.0003, RR = 3.42), reexploration for bleeding (p = 0.0003, RR
      = 3.77), and the occurrence of postoperative ventricular arrhythmias (p = 0.0007,
      RR = 2.45) emerged as risk factors. Multiple factors affect the early and late
      outcome after ascending aorta surgery; our data suggest that the preoperative
      clinical status of the patients and the priority of surgery and aortic dissection
      are the main determinants of the early results; on the other hand, the early
      postoperative course is the main determinant of the late outcome of hospital
      survivors.

PMID- 9230656
TI  - Mortality after esophagectomy: risk factor analysis.
AB  - Esophageal resection is associated with a high incidence of operative mortality,
      suggesting the need for predictors of operative risk. A retrospective analysis
      was performed for esophagectomy patients using univariate and multivariate
      analyses; relative risks (RR) were calculated. Of the 269 patients, 35 (13%)
      died. The optimal model for the preoperative prediction of risk of mortality was
      defined by age (p = 0.001; RR = 2.6) and performance status (p = 0.04; RR = 1.9).
      Delimiting the data pool using a calculated risk of 0.2 accurately identified
      outcomes in 79% of patients and predicted 41% of deaths. The optimal model for
      the overall prediction of risk of mortality was defined by age (p = 0.001; RR =
      3.9), intraoperative blood loss (p < 0.001; RR = 1.7), pulmonary complications (p
      = 0.002; RR = 6.6), and the need for inotropic support (p = 0.003; RR = 10.2).
      The individual risk of mortality after esophagectomy can be predicted
      preoperatively with a model based on patient age and performance status. The
      findings underscore the importance of preoperative evaluation of cardiopulmonary
      function, meticulous operative technique, and aggressive respiratory care in the
      management of the esophagectomy patient.

PMID- 9230658
TI  - Fundoplication avoiding complications of the Nissen procedure: prospective
      evaluation.
AB  - The purpose of this study was to evaluate the results of a fundoplication aimed
      to avoid complications of the Nissen procedure. The procedure combined a
      posterior hemifundoplication and a short circular fundoplication and their
      fixation to crura. A total of 67 consecutive patients were prospectively
      evaluated before and after surgery (median follow-up 24 months). Typical and
      atypical signs of reflux were present in 96.9% and 28.1% of cases, respectively,
      before operation versus 12.5% and 6.3% after. Patients alleged dysphagia in 26.6%
      of cases before surgery and 20.3% after. After operation belching and vomiting
      were impossible in 6.3% and 29.7% of cases, respectively. The pH test did not
      demonstrate any pathologic acid esophageal exposure in 93.3% cases after surgery.
      The mean duration of acid esophageal exposure was 45.1 +/- 21.8% (10-100%) before
      operation versus 1.9 +/- 4.9% (0-30%) after (p < 0.001). The mean lower
      esophageal sphincter pressure increased from 12.4 +/- 6.1 cm H2O (0-28 cm H2O)
      before operation to 20.5 +/- 7.3 cm H2O (11-50 cm H2O) after (p < 0.0001). The
      velocity of esophageal waves increased from 2.8 +/- 1.1 cm/sec (1.2-5.5) before
      surgery to 3.1 +/- 1.5 cm/sec (1.4-7.7 cm/sec) after (p < 0.001). None of the
      Nissen complications were observed, and it was not necessary to reoperate any
      patient. In conclusion, this procedure is effective, improves esophageal motor
      activity, and prevents the occurrence of complications of the Nissen procedure.
      It does not, however, alleviate side effects.

PMID- 9230657
TI  - Tailored antireflux surgery for gastroesophageal reflux disease: effectiveness
      and risk of postoperative dysphagia.
AB  - The Nissen fundoplication is not the proper antireflux procedure for patients
      with poor esophageal peristalsis as it does not strengthen impaired esophageal
      peristalsis. The aim of this study was to investigate if tailoring of antireflux
      surgery according to esophageal contractility is an effective treatment of
      gastroesophageal reflux disease (GERD) with a low incidence of postoperative
      dysphagia. The Toupet fundoplication was laparoscopically performed on 32
      patients with poor esophageal peristalsis and the Nissen fundoplication on 17
      patients with normal peristalsis. After a median follow-up of 15 months, only 1
      of the 49 patients (2.04%) complained of heartburn. Acute esophagitis was found
      in none of them on endoscopy. Of 40 patients tested postoperatively, 2 (5%)
      underwent pathologic esophageal pH monitoring. Postoperative dysphagia was found
      in two patients (4.1%) compared with 25 (51%) preoperatively (p < 0.05). There
      was a significant reduction of dysphagia following the Toupet fundoplication.
      Both procedures increased the resting pressure of the lower esophageal sphincter
      (LES) significantly, which was more pronounced following the Nissen
      fundoplication. Relaxation of the LES was significantly better following the
      Toupet than after the Nissen fundoplication. There was significant improvement of
      esophageal peristalsis following the Toupet fundoplication. Tailored antireflux
      surgery is an effective strategy for treatment of GERD. The incidence of
      postoperative dysphagia is low owing to improvement of impaired esophageal
      peristalsis following the Toupet fundoplication. It may be due to the fact that
      the Toupet fundoplication causes less esophageal outflow resistance than the
      Nissen fundoplication.

PMID- 9230659
TI  - New approach to surgical management of early esophageal thoracic perforation:
      primary suture repair reinforced with absorbable mesh and fibrin glue.
AB  - Esophageal perforation is a life-threatening situation and represents a major
      therapeutic challenge. Results have improved in recent years particularly as a
      result of progress in antibiotic therapy and the use of total parenteral
      nutrition. Surgical management retains a predominant role, involving early
      primary closure and thoracic drainage. We have made an addition to the surgical
      management by applying an absorbable mesh and fibrin glue to the repaired site.
      Seven patients (ages 38-79 years) were treated as described. The mean interval
      from leak to surgery was 28 hours. Six patients had an uneventful postoperative
      course with a mean hospital stay of 34 days (range 26-45 days). In one case the
      technique failed and the patient required an exclusion-diversion procedure. All 7
      patients recovered without mortality. We believe that this technique provides a
      real improvement for this precarious esophageal repair.

PMID- 9230661
TI  - Predictive factors for conversion of laparoscopic cholecystectomy.
AB  - Reliable predictive factors for conversion of laparoscopic cholecystectomy (LC)
      would be extremely useful in the preparation and planning of admission for
      patients with symptomatic cholelithiasis. Data from 783 patients in whom LC was
      attempted in a university clinic from June 1990 to December 1995 were
      retrospectively analyzed. The aim of this study was to determine preoperative
      indicators that can be useful for predicting conversion to open cholecystectomy
      (OC). Conversion was required in 58 (7.4%) patients, of which 48 (83%) were
      elective and 10 (17%) emergency. Factors evaluated were age, sex, obesity,
      duration of gallstone disease, co-morbid factors, indication for surgery,
      previous abdominal surgery, fever, physical examination findings, white blood
      cell (WBC) count, liver function tests, ultrasound findings, and the experience
      of the surgeon. Acute cholecystitis, rigidity in the right upper abdomen, fever,
      thickened gallbladder wall on ultrasonography, elevated alkaline phosphatase
      (ALP), liver transaminases and the WBC count were significant predictors of
      conversion in the univariate analysis. Multivariate logistic regression analysis
      on these significant predictors showed that acute cholecystitis [odds ratio (OR)
      = 3.12], thickened gallbladder wall on ultrasonography (OR = 3.75), elevated ALP
      (OR = 2.23), and WBC count (OR = 3.69) were jointly significant.

PMID- 9230660
TI  - Lack of benefit of combined pancreaticosplenectomy in D2 resection for proximal
      third gastric carcinoma.
AB  - Of the 2790 patients with gastric carcinoma who underwent surgery between January
      1978 and December 1993, there were 224 who underwent a D2 resection for cancer of
      the proximal third of the stomach. Survival in these patients was retrospectively
      analyzed with special reference to the survival benefit of pancreaticosplenectomy
      (PS). The D2 resection involved a splenectomy in 129 patients, a PS in 38
      patients, and neither in 57 patients, with 5-year survivals of 74%, 59%, and 91%,
      respectively. Although these differences in survival were attributable to the
      apparent deviation in the incidence of prognostic variables, no significant
      survival benefit of PS was observed for patients with the same clinical stage
      disease (stages II and III) or the same modal status (n1 and n2). Because PS was
      associated with a significant increase in the incidence of anastomotic dehiscence
      and length of hospital stay, the dismal survival benefit implies that it should
      not be performed routinely with the D2 resection but should be employed only for
      lesions with direct invasion of the pancreas.

PMID- 9230662
TI  - Prognostic significance of proliferative cell nuclear antigen in carcinoma of the
      extrahepatic bile duct.
AB  - Bile duct cancers are still difficult to cure, and even if curatively resected
      locoregional recurrences are frequent. Biologic proliferative activity of the
      cancer may influence postoperative recurrence and the prognosis. A retrospective
      study was performed with the medical records of 44 consecutive patients who
      underwent surgery for histologically extrahepatic bile duct cancer (stage 3 or 4)
      at Osaka Police Hospital during the period 1980 to 1992. Univariate analysis
      suggested that the stage according to the UICC classification, curability, DNA
      ploidy, proliferating cell nuclear antigen (PCNA), S-phase and G2M-phase
      fractions, and histologic differentiation were significant prognostic factors.
      The Cox's proportional hazard model indicated that PCNA and histologic
      differentiation were independent prognostic factors for crude and cause-specific
      survival. When PCNA was omitted from the analysis, DNA ploidy and histologic
      differentiation were independent prognostic factors for both crude and cause
      specific survival. These results suggested that proliferative activity influenced
      the postoperative prognosis of extrahepatic bile duct cancer.

PMID- 9230663
TI  - Comparison of pancreatogastrostomy and pancreatojejunostomy after
      pancreatoduodenectomy performed by one surgeon.
AB  - Pancreatogastrostomy (PG) for restoring pancreaticoenteric continuity after
      pancreatoduodenectomy (PD) has been recommended by a few surgeons on the basis of
      certain theoretic and practical advantages of this procedure over
      pancreatojejunostomy (PJ). The purpose of this study was to determine whether PG
      can be a safe alternative to PJ. Eighty-six PDs performed by the same surgeon for
      periampullary carcinoma were analysed to compare early and late postoperative
      results of PJ (n = 38) and PG (n = 48). The two groups were comparable for age,
      sex, diagnosis, stage, and operation time. PJ leakage developed in six patients
      (15.8%) and PG leakage in one (2.1%) (p < 0.05). Overall rates of
      morbidity/hospital mortality were 34.2/7.9% and 18.8/4.2% in the PJ and PG
      groups, respectively. In conclusion, PG showed a more favorable early outcome
      than PJ. PG is recommended for surgeons who encounter difficulties with PJ for
      reconstruction after PD.

PMID- 9230664
TI  - Reoperative thyroid surgery.
AB  - Reoperative thyroid surgery is an uncommon operation associated with a high
      complication rate. We retrospectively reviewed the data of 115 patients to study
      the incidence of complications after reoperative thyroid surgery. There were 107
      women and 8 men (13.4:1.0) with an average age of 42.8 years (range 18-80 years).
      The most frequent indication for reoperation was completion thyroidectomy for a
      carcinoma identified by permanent sections (50 patients, 43.5%). Reoperative
      surgery was performed on 13 (11.3%) patients with recurrent thyroid cancer. The
      remaining 52 patients underwent reoperation for recurrent thyrotoxicosis (12
      patients, 10.4%), recurrent nodular goiter (28 patients, 24.3%) or recurrent
      multinodular goiter (12 patients, 10.4%). Seven patients with recurrent nodular
      goiter and one patient with recurrent thyrotoxicosis underwent total
      thyroidectomy for the presence of malignancies that were identified by frozen
      sections. Overall, the interval between the initial and reoperative procedures
      ranged from 1 day to 33 years (2335 +/- 272 days). The length of hospital stay
      was 5.8 +/- 0.5 days. The length of time needed for reoperative thyroid surgery
      was 122.0 +/- 6.2 minutes. There was no 30-day perioperative mortality. The
      postoperative complications consisted of transient hypoparathyroidism in six
      patients (5.2%), permanent hypoparathyroidism in two patients (1.7%), transient
      RLN palsy in 3 patients (2.6%), and permanent recurrent laryngeal nerve palsy in
      two patients (1.7%). Reoperative thyroid surgery can be performed safely with
      little morbidity to the patient.

PMID- 9230665
TI  - Bullets and their role in sepsis after colon wounds.
AB  - The objective of this study was to determine the relation between the presence of
      a bullet (gunshot) after injury to the colon and the incidence of sepsis in its
      track and the soft tissue where it is retained. A retrospective review was
      carried out of the charts of consecutive patients admitted for abdominal gunshot
      wounds with proved colon injury during laparotomy where the bullet was either
      retained in the soft tissue or exited the body. The review covered a period of 4
      years beginning January 1, 1990. Three groups were identified for analysis: (1)
      patients from whom the bullet was surgically removed, with additional cleansing
      and debridement of the area (n = 21); (2) patients who did not undergo surgical
      removal of the bullet (n = 81); and (3) patients in whom the bullet exited
      spontaneously and in whom only debridement of the skin was carried out (n = 83).
      Similar risk factors were noted among the groups (age, ATI score, colostomy
      rate), except for a higher incidence of shock in group 3 (p = 0.003). The
      incidence of sepsis in soft tissue was least in group 1. It was five and seven
      times greater in groups 2 and 3, respectively. After an abdominal gunshot with
      colon injury, the missile should be removed if feasible and the local tissue
      debrided. If the bullet has exited spontaneously, its internal track must be
      debrided and lavaged extensively.

PMID- 9230667
TI  - Sir Thomas Peel Dunhill (1876-1957).

PMID- 9230666
TI  - Restorative proctocolectomy or rectum-preserving surgery in patients with
      familial adenomatous polyposis: results of a prospective study.
AB  - Surgical treatment of familial adenomatous polyposis (FAP) is still
      controversial. From 1984 we carried out a prospective evaluation of total
      colectomy with ileorectal anastomosis (IRA) and restorative proctocolectomy with
      ileal pouch-anal anastomosis (IPAA) to determine differences in postoperative
      complications, functional results, occurrence of desmoids, and recurrence of
      polyps in the rectal stump. IRA was performed below the peritoneal reflection and
      was indicated in the absence of rectal cancer and in the presence of fewer than
      10 polyps or minute polyposis in the last 10 cm of the rectal mucosa. IRA
      patients underwent a regular endoscopic follow-up and prolonged sulindac
      administration (100 mg twice daily). When criteria for IRA were absent, IPAA was
      performed adopting a manual anastomosis at the pectinate line. Fourteen patients
      were operated with IRA and 24 with IPAA. There was no difference in sex and age
      between the two groups of patients. The number of rectal polyps was significantly
      different in the two groups. Immediate postoperative complications were observed
      in only five IPAA patients, three of whom (12%) required reoperation. Late
      postoperative complications occurred more frequently in IRA patients (14%) than
      in IPAA patients (4%). Desmoids developed in both groups (five in the IRA group
      and four in IPAA group). The number of bowel movements was similar in both
      groups, but 25% of IPAA patients complained of nocturnal fecal soiling.
      Fulguration or polypectomy for recurrent polyps was necessary in all but two IRA
      patients at follow-up. The rectal stump was easily eradicated by polyps in all
      but four patients with minute polyps at surgery. In the latter patients a diffuse
      or carpeting rectal polyposis occurred. IPAA can give optimum control of
      colorectal polyposis in FAP patients with an acceptable incidence of
      postoperative complications and satisfactory functional results. This type of
      surgical procedure is indicated in most FAP patients, and IRA should be reserved
      for patients without polyps or with fewer than 10 polyps in the rectal stump;
      otherwise growth of polyps cannot be adequately controlled.

PMID- 9230668
TI  - War surgeon of the twentieth century.

PMID- 9230669
TI  - A thought-provoking insight into the current and future use of recombinant
      technology as an alternative to human blood.

PMID- 9230670
TI  - In vitro activity of climbazole, clotrimazole and silver-sulphadiazine against
      isolates of Malassezia pachydermatis.
AB  - Malassezia pachydermatis is a yeast-like, mainly zoophilic fungus, also known as
      Malassezia canis. It can be isolated in 20-50% from normal ear cerumen specimen
      from dogs or cats and has an even higher prevalence in non-suppurative otitis
      externa in animal species such as these. The genus Malassezia contains the two
      species M. furfur, a mainly anthropophilic fungus which physiologically occurs on
      human skin, and M. pachydermatis. We performed Minimal Inhibitory Concentration
      (MIC)-testings of 40 clinical isolates of M. pachydermatis against climbazole
      (CLIM), clotrimazole (CLOT) and silver-sulphadiazine (SILV). While CLOT and CLIM
      are broad-spectrum antimycotics of the azole-type, SILV is a sulphonamide
      compound with antibacterial and antimycotic properties used topically in
      veterinary medicine. For CLIM, the range of MICs was between < 0.06 and 1
      micrograms/ml with an empirical median mean of 0.06 microgram/ml; for CLOT the
      range was between < 0.06 and 32 micrograms/ml (mean = 4 micrograms/ml),
      respectively. The MICs for SILV ranged between 0.25 and > 64 micrograms/ml (mean
      = 16 micrograms/ml) against all tested strains. In conclusion, the two azole
      antimycotics CLIM and CLOT showed good in vitro activity against M.
      pachydermatis. The activity of CLIM was even higher than that of CLOT, which
      might be due to the better water solubility of CLIM. The activity of SILV was
      significantly lower.

PMID- 9230671
TI  - Possible migration of harderian gland immunoglobulin A bearing lymphocytes into
      the caecal tonsil in chickens.
AB  - This study was designed to evaluate the significance of the Harderian gland (HG)
      in the chicken IgA-production system by investigating the influence of HG on the
      increase of surface IgA (sIgA)-positive cells in other lymphoid organs and also
      the possibility of migration of HG lymphocytes into other organs. Non-contact
      culture of splenic or caecal tonsil (CT) lymphocytes with HG whole cells did not
      enhance the expression of sIgA. The experiment of HG lymphocyte transfer showed
      that the transferred HG lymphocytes migrated mainly into the CT in the 3-week-old
      recipient, and mainly into the CT and bursa of Fabricius (BF) in the 6-week-old
      recipient. It was also found that the transferred sIgA-positive HG lymphocytes
      migrated selectively into CT in both 3-week-old and 6-week-old recipients. These
      results indicated that chicken HG plays a central role not only in governing the
      local immunity in the eyes and respiratory tract but also as an organ which
      supplies precursory IgA-producing cells involved in local immunity in the
      intestine.

PMID- 9230672
TI  - Antibiotic residues and prevalence of mastitis pathogen isolation in heifers
      during early lactation following prepartum antibiotic therapy.
AB  - The present study was conducted to determine if antibiotic treatment of heifer
      mammary glands earlier in the prepartum period reduced the occurrence of residues
      in milk without compromising efficacy in treatment of intramammary infections.
      Heifers were assigned randomly to two groups: 1. untreated negative control (n =
      42); and 2. intramammary infusion of 200 mg cephapirin sodium (n = 40) 14 days
      prior to expected calving. Mammary secretions were collected before treatment and
      during early lactation, and were analyzed for residues by the Bacillus
      stearothermophilus disc assay. Only four of 127 samples (3.1%) obtained from
      cephapirin-treated mammary glands at 3 days after calving were positive for
      residues and most (three of four) were from a heifer that calved within 3 days of
      treatment. Mammary secretions were also collected before treatment, and at 3 and
      30 days after calving for microbiological evaluation. For untreated control
      heifers, mastitis pathogens were isolated from 67.3% of samples obtained from
      mammary glands 14 days prior to expected calving, 55.6% obtained 3 days after
      calving and 36.4% of samples obtained 30 days postpartum. A similar percentage of
      samples (63.8%) was positive for mastitis pathogens at 14 days before expected
      calving prior to antibiotic treatment. However, only 15.1% of samples obtained at
      3 days after calving and 7.9% of samples obtained 30 days postpartum from mammary
      glands of antibiotic-treated heifers contained mastitis pathogens. Coagulase
      negative staphylococci were isolated most frequently. Intramammary infusion of
      antibiotics earlier in the prepartum period markedly reduced the occurrence of
      residues in milk during early lactation without affecting efficacy.

PMID- 9230673
TI  - Computer aided assignment of motile Aeromonas strains to genospecies level by
      standard biochemical tests.
AB  - A procedure is given for differentiation of motile Aeromonas spp. Based on nine
      to 12 biochemical properties it allows an assignment of isolated Aeromonas
      strains first to phenotypes and, in the second step, to hybridization groups
      (HGs) 1-13 as well as to the genotypically defined species Aer. allosaccharophila
      and Aer. encheleia. The computer aided classification is carried out according to
      the principles of numerical taxonomy. Using this differentiation scheme 23
      Aeromonas strains, which were isolated from food, and two reference strains were
      speciated. A total of 16 strains were assigned to Aer. hydrophila, six strains to
      Aer. caviae and one strain to Aer. sobria. Of the 16 Aer. hydrophile strains, 11
      were attached to HG 1, one to HG 2 and four could not be classified clearly as HG
      3 or HG 1. All six Aer. caviae isolated were assigned to HG 5 and the Aer. sobria
      strain was ranked among HG 8. The reference strains were assigned to the same
      genotypes by this method than by DNA-DNA hybridization assays.

PMID- 9230674
TI  - Experimental infection with Ehrlichia phagocytophila and Babesia divergens in
      cattle.
AB  - Nine Norwegian Red Cattle, 9-12 months old, were inoculated simultaneously with
      Ehrlichia (Cytoecetes) phagocytophila and Babesia divergens. Ten cattle of the
      same breed and age were kept as controls. Clinical evaluation was done on a daily
      basis and rectal temperatures were recorded every morning for 4 weeks post
      inoculation. Blood and serum samples were collected regularly during the
      observation period. Sera were examined for the presence of antibodies to E.
      phagocytophila and B. divergens by an indirect immunofluorescence antibody test.
      All infected animals showed two periods of fever that corresponded to the
      proliferation of B. divergens and E. phagocytophila in the peripheral blood. The
      simultaneous infection did not induce more severe clinical symptoms than
      infection with either organism alone. Compared with the control group, there was
      a 25% decrease in the mean haematocrit. The leukogram showed a biphasic pattern
      and corresponded to the changes seen in infection with either organism alone. The
      simultaneous infection did not suppress antibody formation towards E.
      phagocytophila or B. divergens.

PMID- 9230675
TI  - Molecular and phenotypic features of aeromonads isolated from snails (Helix
      aspersa) affected with a new summer disease.
AB  - Forty-four aeromonads were isolated during the summer of 1994 from snails (Helix
      aspersa) affected or not by a newly described disease. Snta 1 rRNA gene
      restriction patterns (ribotyping) and nine selected conventional phenotypic tests
      were performed to retrospectively determine relationships among these isolates
      regarding the disease. Results from ribotyping were found highly discriminant in
      strain differentiation and suggest the possible existence of a group of Aeromonas
      associated with the disease. Biochemical and molecular characterizations
      indicated that most of these disease-associated aeromonads could belong to the
      phenospecies A. hydrophila. Phenospecies of aeromonads from healthy snails were
      distinct from those isolated from diseased snails and could be identified as A.
      caviae or remained undetermined. To the authors' knowledge, this is the first
      report of a probable pathogenic aeromonad found in snails, extending the host
      pathogen spectrum of Aeromonas.

PMID- 9230676
TI  - A fatal case of Listeria endocarditis in a man following his tending of goats
      suggests an epidemiological link which is not supported by the results.
AB  - A man died in endocarditis due to listeriosis in the late autumn. He had been
      looking after two goats during the summer. Listeria monocytogenas was isolated
      from a rectal swab from one of the goats. The goat faeces isolate and the human
      blood isolate were of identical serovar. The two isolates, however, were shown to
      be different by multilocus electrophoretic enzyme analysis and ribotyping, as
      well as by biotyping. Thus, these results do not support the hypothesis that the
      man was infected by the goat.

PMID- 9230677
TI  - Generation of biotin/avidin/enzyme nanostructures with maskless photolithography.
AB  - Micrometer-sized domains of a carbon surface are modified to allow derivatization
      to attach redox enzymes with biotin/avidin technology. These sites are spatially
      segregated from and directly adjacent to electron transfer sites on the same
      electrode surface. The distance between these electron transfer sites and enzyme
      loaded domains must be kept to a minimum (e.g., less than 5 microns) to maintain
      the fast response time and high sensitivity required for the measurement of
      neurotransmitter dynamics. This is accomplished through the use of
      photolithographic attachment of photobiotin using an interference pattern from a
      UV laser generated at the electrode surface. This will allow the construction of
      microscopic arrays of active enzyme sites on a carbon fiber substrate while
      leaving other sites underivatized to facilitate electron transfer reactions of
      redox mediators, thus maximizing enzyme activity and detection of the enzyme
      mediator. The ultimate sensitivity of these sensors will be realized only through
      careful characterization of the carbon electrode surface with respect to its
      chemical structure and electron transfer properties following each step of the
      enzyme immobilization process. The characterization of specific modifications of
      micrometer regions of the carbon surface requires analytical methodology that has
      both high spatial resolution and sensitivity. We have used fluorescence
      microscopy with a cooled CCD imaging system to visualize the spatial distribution
      of enzyme immobilization sites (indicated by fluorescence from Texas Red-labeled
      avidin) across the carbon surface. The viability of the enzyme attached to the
      surface in this manner was demonstrated by imaging the distribution of an
      insoluble, fluorescent product. An atomic force microscope was used to obtain
      high-resolution images that probe the heterogeneity of the enzyme sites.

PMID- 9230679
TI  - Application of optical chromatography to immunoassay.
AB  - Optical chromatography, a new separation technique involving the use of a
      radiation force and a medium flow, is used for trace analysis of protein. Two
      polystyrene beads, coated with antibody (anti-mouse IgG), are combined in the
      presence of an antigen (mouse IgG). The bound (B) and free (F) beads are readily
      separated by optical chromatography, and the B/F ratio can be correlated with the
      concentration of antigen (protein). Nanomolar concentrations of protein can be
      measured by this technique. The rates of the forward and reverse immunological
      reactions were independently determined by measuring the time of formation and
      dissociation, respectively, of the immunobeads.

PMID- 9230678
TI  - A conducting salt-based amperometric biosensor for measurement of extracellular
      lactate accumulation in ischemic myocardium.
AB  - In this paper, fabrication, characterization, and physiological application of a
      miniaturized amperometric lactate biosensor are described. The sensor is based on
      cross-linked lactate oxidase and tetrathiafulvalene-tetracyano-quinodimethane
      (TTF-TCNQ) charge transfer complex. The sensor was developed for continuous
      quantitative measurement of the lactate accumulation in ischemic myocardium under
      severe depletion of oxygen. The sensor was evaluated in vitro at an applied
      potential of 0.15 V vs Ag/AgCl; it proved to combine all the performance
      characteristics desired for the present application, such as proper response in
      absence of oxygen, good operational stability, good accuracy and precision (103.5
      +/- 1.2%), adequate response time (t95% = 80 s), and wide linear dynamic range up
      to 27 mM (r = 0.9998) in N2-saturated solutions and at 37 degrees C. The prepared
      sensors (n = 12) showed sensitivity of 380 +/- 90 nA/mM, and a background current
      of 240 +/- 50 nA. The lower limit of detection is 0.4 +/- 0.15 mM with a S/N
      ratio equal to 3. Results obtained for direct lactate monitoring in ischemic
      rabbit papillary muscle under no-flow conditions and PO2 < 6 mm Hg are presented.

PMID- 9230680
TI  - Calicheamicin derivatives conjugated to monoclonal antibodies: determination of
      loading values and distributions by infrared and UV matrix-assisted laser
      desorption/ionization mass spectrometry and electrospray ionization mass
      spectrometry.
AB  - Calicheamicin derivatives (MW approximately 1500) and monoclonal antibodies
      (MoAbs) conjugated to calicheamicin derivatives (MW approximately 150,000) were
      analyzed by UV-MALDI/MS, IR-MALDI/MS, and ESI/MS. These materials are potent
      anticancer agents. Calicheamicin derivatives and conjugates rapidly degrade upon
      UV irradiation but are relatively stable during IR irradiation and under ESI
      conditions. A unique feature of IR-MALDI/MS is a 2 times enhancement in
      resolution relative to UV-MALDI/MS for masses above approximately 50,000 Da
      resulting in a molecular ion envelope containing a series of partially resolved
      peaks of the calicheamicin-MoAb conjugates. The mass shift difference between the
      peak maxima corresponded to the mass change due to the covalent addition of
      calicheamicin derivatives to the monoclonal antibody. The distribution of the
      calicheamicin derivatives in the monoclonal antibodies was computed by
      deconvoluting the partially resolved peak envelope. A unique feature of the ESI
      mass spectra, under unit resolution conditions, is that the distribution of the
      carbohydrates can be well resolved for pure MoAbs and can be only partially
      resolved for conjugated MoAbs. Average loading values for calicheamicia
      derivatives when conjugated to MoAbs were computed from UV-MALDI/MS, IR-MALDI/MS,
      and ESI/MS data and the results compared with the average loading values obtained
      by UV absorption spectrometry. Very low average loading values were computed from
      UV-MALDI/MS data due to the degradation of the conjugated calicheamicin
      derivatives during the UV irradiation process. The IR-MALDI/MS average loading
      values, obtained with glycerol as the matrix, were consistent with the UV
      absorption spectrometry values for conjugates having hydrolytically stable
      linkers, but not when the linker contained a hydrolytically labile hydrazone.
      ESI/MS average loading values were generally lower than the corresponding values
      obtained by IR-MALDI/MS. The average loading values and distributions obtained
      using IR-MALDI/MS were more reliable than the corresponding ESI/MS values because
      the partially resolved, singly and doubly charged peaks in the IR-MALDI spectra
      can be mathematically deconvoluted, while the overlapping, highly multiply
      charged peaks of the electrospray spectra can only be partially deconvoluted.

PMID- 9230682
TI  - Capillary isoelectric focusing of physiologically derived proteins with on-line
      desalting of isotonic salt concentrations.
AB  - Capillary isoelectric focusing within capillaries (cIEF) is a powerful and
      practical method for high-resolution separation of components within complex
      biological mixtures. However, a major problem has always existed; separation
      performance is usually degraded by the presence of salts within the sample.
      Normally this requires the removal of these components by some off-line sample
      cleanup method, prior to analyte separation by cIEF. In this study, we have shown
      it is possible to efficiently remove high salt levels from samples by on-line
      voltage ramping of the applied CE voltage. To allow this technique to be used
      effectively, a customized version of an existing method to internally coat a
      fused-silica capillary has been developed and examined for interexperimental
      reproducibility. We describe the systematic examination of the desalting process
      and its optimization through the use of model protein systems. Furthermore, we
      demonstrate the automated application of this on-line desalting cIEF scheme to
      studies of whole human blood and human cerebrospinal fluid which have undergone
      no manipulation or work up prior to cIEF analysis.

PMID- 9230683
TI  - Microanalysis of lung airway surface fluid by capillary electrophoresis with
      conductivity detection.
AB  - The thin layer of fluid that covers the surface of the epithelia lining the
      conducting airways plays an important role in primary pulmonary defense, and its
      composition may be a critical factor in the pathogenesis of several lung diseases
      including cystic fibrosis. Despite its physiological importance, the composition
      of airway surface fluid (ASF) is poorly understood due to considerable
      difficulties in sample collection from the 5-30 microns thick layer and
      subsequent analysis. We have used a novel technique for sample collection and
      microanalysis of ASF (nanoliter sample required) by capillary electrophoresis
      with conductivity detection. Limitations on the diameters of capillary required
      for the sample injection process and for the conductivity detector require the
      use of coupled separation capillaries with different external diameters. Two
      different methods were used to construct a butt-joint coupling for capillaries of
      different outer diameters. Reasonable efficiency is observed with the coupled
      capillaries (N = 100000 plates m-1) compared to an unbroken single capillary (N =
      180000 plates m-1). The use of conductivity detection allows greater flexibility
      in method development and the possibility of determining a greater variety of
      ions than with a previous indirect-UV method. In the present study, we describe
      the analysis of cations (Na+, K+, Ca2+, Mg2+) and anions (Cl-, NO2-, NO3-, SO4(2
      ), PO4(2-), HCO3-) in rat ASF. Particular attention was paid to developing
      washing procedures which limited fouling of the conductivity sensor. In healthy
      rats, ASF was found to be hypotonic compared to plasma levels, consistent with
      some observations made in human airways.

PMID- 9230684
TI  - 2-Methyl-3-oxo-4-phenyl-2,3-dihydrofuran-2-yl acetate: a fluorogenic reagent for
      detection and analysis of primary amines.
AB  - A new fluorogenic reagent, 2-methyl-3-oxo-4-phenyl-2,3-dihydrofuran-2-yl acetate,
      has been developed for the analysis of primary amines and aminated carbohydrates
      by means of HPLC, CE, and MALDI/MS. Peptides at 1 pmol (2 x 10(-7) M) levels were
      successfully labeled and analyzed through CE. The fluorescent derivatives have
      good stability in both acidic and basic solutions, making their further
      manipulation and structural analysis possible. The derivatives can be analyzed in
      reversed-phase HPLC due to the hydrophobic nature of this fluorescent tag.
      Characteristic elution intervals between the diastereomeric peaks of the chiral
      peptide derivatives may be used in structural verification. The labeled peptides
      and neutral oligosaccharides are also readily detectable through MALDI/MS in its
      positive mode.

PMID- 9230686
TI  - Dorso-ventral limb polarity and origin of the ridge: on the fringe of
      independence?
AB  - Molecular and developmental studies of limb pattern formation have recently
      gained widespread attention. The fact that vertebrate limbs are amenable to both
      genetic and embryological manipulations has established this model system as a
      valuable paradigm for studying vertebrate development. Limb buds are polarised
      along all three major axes and the establishment of the dorso-ventral (DV)
      polarity is dependent upon cues localised in the trunk, where a DV ectodermal
      interface is produced by confrontation of dorsal and ventral identities. By
      analogy to Drosophila imaginal disc development, this interface has been proposed
      to determine and position an ectodermal organising centre, the Apical Ectodermal
      Ridge (AER), controlling limb bud outgrowth. Recent fate mapping studies and
      studies of genes regulating DV limb polarity, AER formation and differentiation
      suggest, however, that DV patterning and AER induction, though coordinately
      regulated during limb bud outgrowth, may early on be more dissociated than
      expected.

PMID- 9230687
TI  - Homeosis and polyposis: a tale from the mouse.
AB  - Homeobox genes play essential roles in specifying the fates of different cell
      types during embryogenesis. In Drosophila, the homeotic gene caudal is important
      for the generation of posterior structures. In the mouse, the caudal homologue
      Cdx2 has been implicated in directing early processes in intestinal morphogenesis
      and in the maintenance of the differentiated phenotype. A recent study showed
      that Cdx2 null mutation was embryonically lethal, whereas Cdx2+/- mice developed
      multiple intestinal polyps in the proximal colon in addition to developmental
      defects. There are striking phenotypic similarities and differences between
      Cdx2+/- and other mice predisposed to intestinal neoplasia. The possible role of
      Cdx2 in human colorectal tumorigenesis is discussed.

PMID- 9230688
TI  - A telomerase mutant defective in sister chromatid separation at mitosis.
AB  - The telomere is a functional domain of the chromosome, located at the extreme
      ends, and is essential for normal chromosome stability. Chromosomes lacking
      telomeres are inherited improperly, and mutations in the telomeric repeat
      sequences are thought to lead to senescence and possibly to cancer. The molecular
      mechanisms maintaining chromosomes by telomeres, however, have been unclear.
      Results recently reported by Kirk et al, offer an insight into new telomerase
      function. They have identified a novel telomerase mutation that blocks sister
      chromatid separation in mitosis.

PMID- 9230689
TI  - Structural studies on myosin II: communication between distant protein domains.
AB  - Understanding how chemical energy is converted into directed movement is a
      fundamental problem in biology. In higher organisms this is accomplished through
      the hydrolysis of ATP by three families of motor proteins: myosin, dynein and
      kinesin. The most abundant of these is myosin, which operates against actin and
      plays a central role in muscle contraction. As summarized here, great progress
      has been made towards understanding the molecular basis of movement through the
      determination of the three-dimensional structures of myosin and actin and through
      the establishment of systems for site-directed mutagenesis of this motor protein.
      It now appears that the generation of movement is coupled to ATP hydrolysis by a
      series of domain movements within myosin.

PMID- 9230690
TI  - The phytochromes: a biochemical mechanism of signaling in sight?
AB  - The biochemical mechanism by which the phytochrome family of plant sensory
      photoreceptors transmit perceived informational light signals downstream to
      transduction pathway components is undertermined. The recent sequencing of the
      entire genome of the cyanobacterium Synechocystis, however, has revealed a
      protein that has an NH2-terminal domain with striking sequence similarity to the
      photosensory NH2-terminal domain of the phytochromes, and a COOH-terminal domain
      strongly related to the transmitter histidine kinase module of bacterial two
      component sensors. The Synechocystis protein is capable of autocatalytic
      chromophore ligation and exhibits photoreversible light-absorption changes
      analogous to the phytochromes, indicating its capacity to function as an
      informational photoreceptor. Together with earlier observations that the COOH
      terminal domains of the plant phytochromes also have sequence similarity to the
      histidine kinases, these data suggest that the cyanobacteria utilize
      photoregulated histidine kinases as a sensory system and that the plant
      phytochromes may be evolutionary descendants of these photoreceptors.

PMID- 9230691
TI  - Transforming growth factor-beta: the breaking open of a black box.
AB  - Transforming growth factor-beta (TGF-beta) and its related proteins regulate
      broad aspects of body development, including cell proliferation, differentiation,
      apoptosis and gene expression, in various organisms. Deregulated TGF-beta
      function has been causally implicated in the generation of human fibrotic
      disorders and in tumor progression. Nevertheless, the molecular mechanisms of TGF
      beta action remained essentially unknown until recently. Here, we discuss recent
      progress in our understanding of the mechanism of TGF-beta signal transduction
      with respect to the regulation of gene expression, the control of cell phenotype
      and the potential usage of TGF-beta for the treatment of human diseases.

PMID- 9230692
TI  - The function of inositol high polyphosphate binding proteins.
AB  - The inositol phosphate metabolism network has been found to be much more complex
      than previously thought, as more and more inositol phosphates and their
      metabolizing enzymes have been discovered. Some of the inositol phosphates have
      been shown to have biological activities, but little is known about their signal
      transduction mechanisms except for that of inositol 1,4,5-trisphosphate. The
      recent discovery, however, of a number of binding proteins for inositol high
      polyphosphate [inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6
      pentakisphosphate, or inositol hexakisphosphate] enables us to speculate on the
      physiological function of these compounds. In this article we focus on two major
      issues: (1) the roles of inositol high polyphosphates in vesicular trafficking,
      especially exocytosis, and (2) pleckstrin homology domain-containing IP4 binding
      proteins involved in the Ras signaling pathway.

PMID- 9230694
TI  - Controlling the molecular motor of neutrophil chemotaxis.
AB  - Our defence against microbes depends largely on the ability of neutrophils to
      migrate from the blood stream to sites of infection. Although the ability of
      animal cells to move may be primitive, and also fundamental for a number of
      phenomena in biology, the cellular mechanism by which neutrophils are able to
      move rapidly towards the infection remains an enigma. Even though the structures
      of the receptors involved have been sequenced and many of the molecules involved
      in neutrophil adherence and traction identified, the essential mechanisms that
      control and regulate the neutrophil motor remain obscure. Here, an outline of the
      fundamental inadequacies in our current understanding is given, along with some
      recent developments that promise to produce some significant advances.

PMID- 9230693
TI  - The SCL/TAL1 gene: roles in normal and malignant haematopoiesis.
AB  - SCL (TAL1/TCL5) is a member of the helix-loop-helix family of transcription
      factors. Originally identified because of its involvement in a tumour-specific
      chromosomal translocation, overexpression of the SCL gene is the most common
      molecular abnormality found in human T cell leukaemia. Transgenic models have now
      formally demonstrated that overexpression of SCL within the T cell lineage is
      capable of causing malignant transformation. Gene targeting experiments have
      revealed that the SCL gene is crucial for the development of primitive
      haematopoiesis in the mouse and is also required for the generation of all adult
      haematopoietic lineages. Biochemical studies have indicated some of the proteins
      which interact with SCL and this has refined the hypotheses concerning the
      mechanisms by which SCL plays a role in leukaemogenesis and haematopoietic
      development.

PMID- 9230695
TI  - Set-aside cells in maximal indirect development: evolutionary and developmental
      significance.
AB  - In the maximal form of indirect development found in many taxa of marine
      invertebrates, embryonic cell lineages of fixed fate and limited division
      capacity give rise to the larval structures. The adult arises from set-aside
      cells in the larva that are held out from the early embryonic specification
      processes, and that retain extensive proliferative capacity. We review the
      locations and fates of set-aside cells in two protostomes, a lophophorate and a
      deuterostome. The distinct adult body plans of many phyla develop from homologous
      set-aside cells within homologous larvae. We argue that the stocks from which
      these phyla arose utilized these respective larvae, and the diversity of their
      adult body plans reflects diverse pattern formation processes executed in their
      set-aside cell populations. Chordates and arthropods develop directly, but share
      adult characters with indirectly developing phyla. Thus the deuterostome and
      protostome stocks that were ancestral to chordates and arthropods, respectively,
      also utilized maximal indirect development.

PMID- 9230696
TI  - Encystation of entamoeba parasites.
AB  - Entamoeba histolytica is a protozoan parasite of humans, and the causitive agent
      of intestinal amebiasis. The disease-causing stage of the parasite is an
      osmotically sensitive ameboid form, which differentiates into a thick-walled cyst
      for transmission from person to person. The conditions within the human intestine
      that induce encystment of the amoeba are unknown, but studies using an amoebic
      parasite of reptiles are now yielding information about the molecules and
      host:parasite interactions involved in the process. An understanding of the
      amoeba's obligatory encystment pathway should provide an approach for
      interrupting the transmission of this parasite, for which there is currently no
      vaccine.

PMID- 9230697
TI  - In pursuit of influenza: Fort Monmouth to Valhalla (and back).
AB  - In reviewing 50 years of personal research on influenza, I have journeyed,
      literally and figuratively, from an army camp epidemic in Fort Monmouth NJ in
      1947 to a (literal and figurative) Valhalla, where I now conduct my research.
      Having entered the field as a physician, I have always sought practical
      applications of my work, yet in every instance, such applications have led me to
      seek further answers in basic research as new questions arose. I entered the area
      of influenza virus genetics by the back door through an interest in the effects
      of corticosteroid hormones on viral replication, used the genetic approach in
      analyzing the morphological variation of the virus and, in so doing, exploited
      the finding of a linkage of high-yield growth to spherical morphology. Today, all
      influenza vaccine viruses are high-yield genetic reassortants. Subsequent study
      of reassortant viruses facilitated the identification and isolation of the two
      major antigens of the virus in antigenic hybrids and showed their differing
      functions in the induction of immunity. In turn, a new approach to influenza
      vaccination has been discovered and is presently under clinical investigation.

PMID- 9230698
TI  - Phonotactics and syllable stress: implications for the processing of spoken
      nonsense words.
AB  - Two experiments using bisyllabic CVCCVC nonsense words that varied in phonotactic
      probability and stress placement were conducted to examine the influences of
      phonotactic and metrical information on spoken word recognition. Experiment 1
      examined participants' intuitions about the phonological "goodness" of nonsense
      words. Experiment 2 examined processing times for the same stimuli in a speeded
      auditory repetition task. The results of both studies provide further evidence
      that the phonotactic configuration and stress placement of spoken stimuli have
      important implications for the representation and processing of spoken words.

PMID- 9230699
TI  - Backwards signing and ASL syllable structure.
AB  - A recurrent question raised by the study of signed languages concerns the
      linguistic effect of the modality in which the language is produced. Is the
      modality difference between speech and sign reflected merely in the nature of the
      phonetic features that map into production and perception, or is it the case that
      there might be higher level organizational differences between the two linguistic
      modalities? The present study addresses the nature of the modality effect inside
      the syllable, namely whether syllables in ASL display evidence of segmental
      composition. Data from backwards signing are presented to demonstrate that the
      phonological representations that must be available to signers when they perform
      backwards signing tasks cannot be adequately represented with the current models
      that posit segmental composition of ASL syllables. Instead, it is argued that it
      is sufficient to make reference to distinctive features, in syllable initial and
      syllable final positions, and that there is no support for any further internal
      segmental divisions.

PMID- 9230700
TI  - Electron transfer quenching of the rose bengal triplet state.
AB  - The potential for electron transfer quenching of rose bengal triplet (3RB2-) to
      compete with energy transfer quenching by oxygen was evaluated. Rate constants
      for oxidative and reductive quenching were measured in buffered aqueous solution,
      acetonitrile and in small unilamellar liposomes using laser flash photolysis.
      Biologically relevant quenchers were used that varied widely in structure,
      reduction potential and charge. Radical ion yields (phi i) were measured by
      monitoring the absorption of the rose bengal semireduced (RB.3-) and semioxidized
      (RB.-) radicals. The results in solution were analyzed as a function of the free
      energy for electron transfer (delta G) calculated using the Weller equation
      including electrostatic terms. Exothermic oxidative quenching was about 10-fold
      faster than exothermic reductive quenching in aqueous solution. The quenching
      rate constants decreased as delta G approached zero in both aqueous and
      acetonitrile solution. Exceptions to these generalizations were observed that
      could be rationalized by specific steric or electrostatic effects or by a change
      in mechanism. The results suggest that electron transfer reactions with some
      potential quenchers in cells could compete with formation of singlet oxygen [O2(1
      delta g)]. Values of phi i were generally greater for reductive quenching and,
      for oxidative quenching, greater in acetonitrile than in buffer. Electron
      transfer quenching of 3RB2- in liposomes, below the phase transition temperature
      was slower than in solution for both lipid-soluble and water-soluble quenchers
      indicating that these reactions may not compete with formation of O2(1 delta g)
      during cell photosensitization.

PMID- 9230701
TI  - Photochemical and photobiological studies with acridine and phenanthridine
      hydroperoxides in cell-free DNA.
AB  - The acridine and phenanthridine hydroperoxides 3 and 7 were synthesized as
      photochemical hydroxyl radical sources for oxidative DNA damage studies. The
      generation of hydroxyl radicals upon UVA irradiation (lambda = 350 nm) was
      verified by trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide and
      benzene. The enzymatic assays of the damage in cell-free DNA from bacteriophage
      PM2 caused by the acridine and phenanthridine hydroperoxides 3 and 7 under near
      UVA irradiation revealed a wide range of DNA modifications. Particularly,
      extensive single-strand break formation and DNA base modifications sensitive to
      formamidopyrimidine DNA glycosylase (Fpg protein) were observed. In the
      photooxidation of calf thymus DNA, up to 0.69 +/- 0.03% 8-oxo-7,8-dihydroguanine
      was formed by the hydroperoxides 3 and 7 on irradiation, whose yield was reduced
      up to 40% in the presence of the hydroxyl radical scavengers mannitol and tert
      butanol. The acridine and phenanthridine hydroperoxides 3 and 7 also induce DNA
      damage through the type I photooxidation process, for which photoinduced electron
      transfer from 2'-deoxyguanosine to the singlet states of 3 and 7 was estimated by
      the Rehm-Weller equation to possess a negative Gibb's free energy of ca -5 kcal/
      mol. Control experiments with the sensitizers acridine 1 and the acridine alcohol
      4 in calf thymus and PM2 DNA confirmed the photosensitizing propensity of the UVA
      absorbing chromophores. The present study emphasizes that for the development of
      selective and efficient photochemical hydroxyl radical sources, chromophores with
      low photosensitizing ability must be chosen to avoid type I and type II
      photooxidation processes.

PMID- 9230702
TI  - Energy transfer spectroscopy for measuring mitochondrial metabolism in living
      cells.
AB  - Microscopic energy transfer spectroscopy was established using mixed solutions of
      reduced nicotinamide adenine dinucleotide (NADH) and the mitochondrial marker
      rhodamine 123 (R123). This method was applied to probe mitochondrial malfunction
      of cultivated endothelial cells from calf aorta incubated with various inhibitors
      of specific enzyme complexes of the respiratory chain. Autofluorescence of the
      coenzyme NADH as well as energy transfer efficacy from excited NADH molecules
      (energy donor) to R123 (energy acceptor) were measured by time-gated fluorescence
      spectroscopy. Because intermolecular distances in the nanometer range are
      required for radiationless energy transfer, this method is suitable to probe
      selectively mitochondrial NADH. Autofluorescence of endothelial cells usually
      exhibited a weak increase after specific inhibition of enzyme complexes of the
      respiratory chain. In contrast, pronounced and statistically significant changes
      of energy transfer efficacy were observed after inhibition of the same enzyme
      complexes. Detection of NADH and R123 in different nanosecond time gates
      following the exciting laser pulses enhances the selectivity and improves
      quantification of fluorescence measurements. Therefore, time-gated energy
      transfer spectroscopy is suggested to be an appropriate tool for probing
      mitochondrial malfunction.

PMID- 9230703
TI  - A preparative method for crosslinking proteins to DNA in nuclei by single-pulse
      UV laser irradiation.
AB  - Photocrosslinking of proteins to DNA by single-pulse UV laser has been used only
      in analytical experiments, carried out with reconstituted complexes of a single
      DNA binding protein and a labeled target sequence. Here we propose a large-scale
      technique for irradiation of nuclei, generating preparative quantities of
      covalently linked protein-DNA complexes for further analysis of the partner
      molecules. The use of a flow cuvette allows a milligram of DNA in either nuclei
      or chromatin to be irradiated by a single pulse within few minutes. The
      efficiency of crosslinking varies from 6 to 12% of the total nuclear proteins.
      The presence of histones and other chromosomal proteins in the crosslinked
      protein-DNA complexes was demonstrated by using specific antibodies. The
      irradiation procedure can be fully automated using a microcomputer.

PMID- 9230704
TI  - Photochemical and photobiological studies of a furonaphthopyranone as a benzo
      spaced psoralen analog in cell-free and cellular DNA.
AB  - Photobiological activities of the benzo-spaced psoralen analog
      furonaphthopyranone 3 have been investigated in cell-free and cellular DNA. The
      molecular geometry parameters of 3 suggest that it should not form interstrand
      crosslinks with DNA. With cell-free DNA no evidence for crosslinking but also not
      for monoadduct formation was obtained; rather, the unnatural furocoumarin 3
      induces oxidative DNA modifications under near-UVA irradiation. The enzymatic
      assay of the photosensitized damage in cell-free PM2 DNA revealed the significant
      formation of lesions sensitive to formamidopyrimidine DNA glycosylase (Fpg
      protein). In the photooxidation of calf thymus DNA by the furonaphthopyranone 3,
      0.29 +/- 0.02% 8-oxo-7,8-dihydroguanine (8-oxoGua) was observed. With 2'
      deoxyguanosine (dGuo), the guanidine-releasing photooxidation products oxazolone
      and oxoimidazolidine were formed predominately, while 8-oxodGuo and 4-HO-8
      oxodGuo were obtained in minor amounts. The lack of a significant D2O effect in
      the photooxidation of DNA and dGuo reveals that singlet oxygen (type II process)
      plays a minor role; control experiments with tert-butanol and mannitol confirm
      the absence of hydroxyl radicals as oxidizing species. The furonaphthopyranone 3
      (Ered = -1.93 +/- 0.03V) should act in its singlet-excited state as electron
      acceptor for the photooxidation of dGuo (delta GET ca -6 kcal/mol), which
      corroborates photoinduced electron transfer (type I) as a major DNA-oxidizing
      mechanism. A comet assay in Chinese hamster ovary (CHO) AS52 cells demonstrated
      that the psoralen analog 3 damages cellular DNA upon near-UVA irradiation;
      however, no photosensitized mutagenicity was observed in CHO AS52 cell cultures.

PMID- 9230705
TI  - Fluorescence and absorption contrast mechanisms for biomedical optical imaging
      using frequency-domain techniques.
AB  - The ability to optically image or detect diseased tissue volumes located deep
      within tissues depends upon the degree of contrast provided by differences in
      local optical properties. In this report, we show that the exogenous contrast
      offered by fluorescent compounds is superior to that provided by nonfluorescing,
      light-absorbing compounds when time-dependent measurements are employed. In
      addition, we show that the induced contrast is not only moderated by the
      preferential uptake of fluorescent agents into diseased tissue volumes of
      interest but also by the fluorescent optical properties and the fluorescence
      dynamics in the specific tissue volume. Using tissue phantom studies, we
      demonstrated experimentally that near-infrared-absorbing and fluorescent dyes
      such as indocyanine green can provide detection of diseased tissue volumes from
      fluorescence measurements made at the periphery of tissue when there is perfect,
      100-fold and 10-fold partitioning in diseased tissues over that in surrounding
      normal tissues. Experimental results of common laser dyes show the contrast is
      also mediated by the quantum yield and lifetime parameters that may be dependent
      upon the local tissue environment.

PMID- 9230706
TI  - Interaction between cytochrome b2 core and flavodehydrogenase from the yeast
      Hansenula anomala.
AB  - The binding of cytochrome b2 core (a monomer) to flavodehydrogenase (a tetramer),
      both purified from Hansenula anomala flavocytochrome b2, has been studied in the
      presence of 2-p-toluidinylnaphthalene-6-sulfonate (TNS). The association constant
      of the TNS-flavodehydrogenase complex was found to be equal to 0.64 microM-1 with
      a stoichiometry of one TNS per tetramer. Binding of cytochrome b2 core to
      flavodehydrogenase was followed by monitoring changes in the TNS fluorescence.
      Our results indicated that the binding is cooperative, with a stoichiometry of
      four cytochrome b2 cores per tetramer of flavodehydrogenase.

PMID- 9230707
TI  - In situ action spectra suggest that DNA damage is involved in ultraviolet
      radiation-induced immunosuppression in humans.
AB  - The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to
      study the immunomodulatory effects of UV radiation. The in vitro action spectrum
      for the MECLR showed that the UV-induced suppression of the MECLR responses is
      associated with UV-induced DNA damage. To investigate whether in vivo DNA damage
      also leads to the abrogation of the MECLR, in situ action spectra were made for
      the MECLR and the induction of thymine dimers (T < > T). Human skin, obtained
      from plastic surgery, was exposed to monochromatic light of 254, 297, 302 and 312
      nm. After irradiation, epidermal cells were isolated and used as stimulator cells
      in the MECLR or processed for flow cytometric detection of T < > T. On the basis
      of dose-response curves for each wavelength, the action spectra for suppression
      of the MECLR and the induction of T < > T were calculated. These spectra showed
      close similarities, suggesting that, also in situ, UV-induced DNA damage is
      involved in the UV-induced suppression of the MECLR. Both action spectra showed a
      small decline from 254 nm to 302 nm, followed by a steep decline to 312 nm. These
      data show that, in situ, UVC can efficiently induce DNA damage and modulate
      cutaneous immune responses.

PMID- 9230708
TI  - Triplet energy transfer between the primary donor and carotenoids in Rhodobacter
      sphaeroides R-26.1 reaction centers incorporated with spheroidene analogs having
      different extents of pi-electron conjugation.
AB  - Three carotenoids, spheroidene, 3,4-dihydrospheroidene and 3,4,5,6
      tetrahydrospheroidene, having 8, 9 and 10 conjugated carbon-carbon double bonds,
      respectively, were incorporated into Rhodobacter (Rb.) sphaeroides R-26.1
      reaction centers. The extents of binding were found to be 95 +/- 5% for
      spheroidene, 65 +/- 5% for 3,4-dihydrospheroidene and 60 +/- 10% for 3,4,5,6
      tetrahydrospheroidene. The dynamics of the triplet states of the primary donor
      and carotenoid were measured at room temperature by flash absorption
      spectroscopy. The carotenoid, spheroidene, was observed to quench the primary
      donor triplet state. The triplet state of spheroidene that was formed
      subsequently decayed to the ground state with a lifetime of 7.0 +/- 0.5
      microseconds. The primary donor triplet lifetime in the Rb. sphaeroides R-26.1
      reaction centers lacking carotenoids was 60 +/- 5 microseconds. Quenching of the
      primary donor triplet state by the carotenoid was not observed in the Rb.
      sphaeroides R-26.1 reaction centers containing 3,4-dihydrospheroidene nor in the
      R-26.1 reaction centers containing 3,4,5,6-tetrahydrospheroidene. Triplet-state
      electron paramagnetic resonance was also carried out on the samples. The
      experiments revealed carotenoid triple-state signals in the Rb. sphaeroides R
      26.1 reaction centers incorporated with spheroidene, indicating that the primary
      donor triplet is quenched by the carotenoid. No carotenoid signals were observed
      from Rb. sphaeroides R-26.1 reaction centers incorporating 3,4-dihydrospheroidene
      nor in reaction centers incorporating 3,4,5,6-tetrahydrospheroidene. Circular
      dichroism, steady-state absorbance band shifts accompanying the primary
      photochemistry in the reaction center and singlet energy transfer from the
      carotenoid to the primary donor confirm that the carotenoids are bound in the
      reaction centers and interacting with the primary donor. These studies provide a
      systematic approach to exploring the effects of carotenoid structure and excited
      state energy on triplet transfer between the primary donor and carotenoids in
      reaction centers from photosynthetic bacteria.

PMID- 9230709
TI  - Rapid tyrosine phosphorylation of HS1 in the response of mouse lymphoma L5178Y-R
      cells to photodynamic treatment sensitized by the phthalocyanine Pc 4.
AB  - The ability of photodynamic treatment (PDT) with the phthalocyanine Pc 4 to
      activate cellular signal transduction pathways in murine lymphoma L5178Y-R cells
      has been assessed by observing increases in protein tyrosine phosphorylation at
      early times post-PDT. Western blot analysis with an anti-phosphotyrosine antibody
      revealed a dramatic increase in phosphorylation of two major protein bands of Mr
      approximately 80,000 and approximately 55,000 in response to PDT. The increase
      was PDT dose-dependent, occurred as early as 20 s after initiation of light
      exposure of Pc 4-preloaded cells and was amplified by the presence of the protein
      tyrosine phosphatase inhibitor, sodium orthovanadate (NaVO4). By
      immunoprecipitation, one of the Mr approximately 80,000 phosphorylated proteins
      has been identified as HS1, a substrate of nonreceptor-type protein tyrosine
      kinases. Although vanadate greatly enhanced the level and extent of PDT-induced
      phosphorylation, it had no influence on overall photocytotoxicity or on the rate
      of apoptotic DNA fragmentation. Genistein, an inhibitor of protein tyrosine
      kinases, diminished tyrosine phosphorylation of the Mr approximately 80,000 and
      other proteins and dramatically potentiated cell killing induced by PDT but did
      not significantly affect PDT-induced apoptosis. The results suggest that PDT
      rapidly activates a membrane-associated src family kinase(s) in L5178Y-R cells,
      one substrate of which is HS1, and that protein tyrosine phosphorylation is part
      of a stress response, protecting a portion of the cells from the lethal effects
      of PDT but not altering the mechanism by which they die.

PMID- 9230710
TI  - Ex vivo application of delta-aminolevulinic acid induces high and specific
      porphyrin levels in human skin tumors: possible basis for selective photodynamic
      therapy.
AB  - In photodynamic therapy with topically applied delta-aminolevulinic acid
      porphyrins are acting as photosensitizers. The profile of porphyrin metabolites
      in normal or in neoplastic skin after administration of delta-aminolevulinic acid
      has not been determined in detail yet. Thus, to study porphyrin biosynthesis in
      human skin an organ culture model was developed. Explant pieces of normal skin,
      keratoacanthoma, and basal cell carcinoma were incubated with 1 mM delta
      aminolevulinic acid for 36 h. Levels of delta-aminolevulinic acid, porphyrins and
      porphyrin metabolites were measured in tissues and supernatants. After incubation
      with delta-aminolevulinic acid, higher porphyrin levels were demonstrated in
      tumors as compared to normal skin. In supernatants, most of formed porphyrins,
      preferentially highly carboxylated porphyrin metabolites, were measured. The
      pattern of synthesized porphyrins differed between normal and neoplastic skin
      explants. In tissues of basal cell carcinomas protoporphyrin was preferentially
      shown and tissues of keratoacanthomas were characterized by a predominance of
      coproporphyrin as compared to normal skin. The results show that explant cultures
      offer an easy approach to examine the porphyrin biosynthesis of various tissues.
      The tumor-specific delta-aminolevulinic acid metabolism indicates additional
      porphyrin metabolites such as coproporphyrin apart from protoporphyrin as
      effective photosensitizers and may offer a novel approach to tumor-selective
      photodynamic damage.

PMID- 9230711
TI  - Seasonal variation in urocanic acid isomers in human skin.
AB  - Urocanic acid (UCA) is a major chromophore for UV in the skin and has been
      suggested to act as an initiator of UV-induced immunosuppression. It converts
      from the naturally occurring trans-isomer to the cis-isomer on UV exposure.
      Isomerization is dose dependent until the photostationary state is reached, and
      the seasonal variation in irradiance from the sun may lead to changes in the
      percentage of UCA present as cis-UCA throughout the year. Thirty young healthy
      subjects, skin types I-IV, were followed from early summer till spring. At each
      of six visits (June, July, August, October, December, March), pigmentation and
      the concentration of UCA isomers were measured at six body sites: forehead, upper
      chest, upper back, outer upper arm, inner upper arm and buttock. In exposed as
      well as unexposed regions a variation in pigmentation was found, peak values
      being recorded in August. Total UCA concentration was lower in July and August
      than in the rest of the year, irrespective of body site. In July, the percentage
      of cis-UCA was close to the maximal obtainable (50-60%) at all sites except the
      buttock. In the three winter months the percentage of cis-UCA was below 7% in all
      regions except for the forehead, where the mean cis-UCA was 18% in October and
      March. No consistent relationship was found between UCA isomers and pigmentation
      or skin type.

PMID- 9230712
TI  - European Association of Cardiothoracic Anaesthesiologists 12th annual meeting.
      Thessaloniki, Greece, 25-28 Jun 1997. Abstracts.

PMID- 9230713
TI  - British Association of Urological Surgeons 1997 annual meeting. 24-27 June 1997.
      Abstracts.

PMID- 9230714
TI  - The 8th International Catecholamine Symposium. Pacific Grove, California, October
      13-18, 1996, Abstracts.

PMID- 9230715
TI  - Joint Meeting of the 16th Biennial Meeting of the International Society for
      Neurochemistry and 28th Annual Meeting of the American Society for
      Neurochemistry. Boston, Massachusetts, July 20-26, 1997. Abstracts.

PMID- 9230716
TI  - 7th Symposium on Mechanisms of Vasodilatation. Maastricht, The Netherlands, July
      6-9, 1997. Abstract.

PMID- 9230717
TI  - Cytomegalovirus: the monster in the closet?

PMID- 9230718
TI  - Inhaled bronchodilator therapy in mechanically ventilated patients.

PMID- 9230719
TI  - Effects of a potent platelet-activating factor antagonist, SR27417A, on allergen
      induced asthmatic responses.
AB  - Platelet-activating factor (PAF) is a lipid-derived mediator that has been
      implicated in the pathophysiology of airway inflammation in asthma. Its actions
      include chemotaxis and activation of inflammatory cells, particularly
      eosinophils. Inhaled PAF causes bronchoconstriction and increased airway
      responsiveness in human subjects. However, PAF antagonists have so far failed to
      show benefits in allergen challenge or in the treatment of chronic asthma.
      SR27417A is a novel PAF antagonist with increased potency compared with
      previously tested compounds. Twelve asthmatic subjects received treatment with
      either SR27417A or placebo for 1 wk in a double-blind crossover study. After
      treatment each subject underwent allergen challenge. Effects were assessed in
      terms of early and late asthmatic responses and allergen-induced effects on
      airway responsiveness. Baseline lung function and airway responsiveness were also
      examined. Treatment with SR27417A significantly attenuated the late asthmatic
      response (AUC LAR4-10h: 107 +/- 24 after placebo, 79 +/- 17 after SR27417A, p <
      0.05; mean maximal percent fall in FEV1 LAR: 29 +/- 6% after placebo, 23.5 +/-
      5.4% after SR27417A, p < 0.05). There were no effects on early asthmatic
      responses, allergen-induced airway responsiveness, or baseline lung measurements.
      SR27417A is the most potent PAF antagonist to date, and it has a modest
      inhibitory effect on the late asthmatic response. This suggests that PAF has a
      small role in allergic inflammation.

PMID- 9230720
TI  - Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in
      mild asthma is not due to bronchodilation.
AB  - Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange
      abnormalities provoked by platelet-activating factor (PAF) challenge in normal
      persons. To further explore the intriguing dissociation between spirometric
      abnormalities and gas exchange defects shown in patients with asthma, we
      investigated whether the salbutamol-induced improvement in gas exchange
      disturbances after PAF is the result of bronchodilation by comparing this effect
      with that of ipratropium bromide. We hypothesized that ipratropium bromide, an
      anticholinergic agent without vascular effects, should block PAF-induced
      bronchoconstriction but not interfere with its systemic, neutropenic, and gas
      exchange effects. We studied eight nonsmokers with mild asthma (26 +/- 2.0 SE yr
      of age) who, prior to PAF challenge (18 micrograms), inhaled either ipratropium
      bromide (80 micrograms) or salbutamol (300 micrograms) in a randomized, double
      blind, crossover fashion 1 wk apart. Peripheral blood neutrophils, respiratory
      system resistance (Rrs), arterial blood gases and ventilation-perfusion (VA/Q)
      inequalities were measured 5, 15, and 45 min after PAF. Compared with
      pretreatment with salbutamol, ipratropium bromide also blocked the increase of
      respiratory system resistance (Rrs) but did not prevent facial flushing and
      neutropenia (p < 0.03) at 5 min nor the decrease of PaO2 (p = 0.08 and 0.05), the
      increase of AaPO2 (p < 0.02 each), and the deterioration of VA/Q relationships (p
      < 0.05 each) at 5 and 15 min, respectively. This functional pattern was similar
      to that observed previously in normal subjects and in nonpremedicated asthmatic
      patients after PAF, with return to baseline values at 45 min. By contrast,
      salbutamol blocked PAF-induced increased Rrs, in addition to all the other PAF
      induced abnormalities. These findings indicate that, in patients with mild
      asthma, salbutamol inhibits PAF-induced neutropenia and gas exchange
      abnormalities by mechanisms involving other than airway smooth muscle narrowing,
      possibly by acting on both the bronchial and pulmonary circulations.

PMID- 9230721
TI  - Sensitization to cat allergen is associated with asthma in older men and predicts
      new-onset airway hyperresponsiveness. The Normative Aging Study.
AB  - To explore the relationship between sensitization to inhalant allergens and adult
      asthma, we performed two nested case-control studies of men being followed in the
      VA Normative Aging Study. In Study A, 46 subjects (mean age, 61.2 +/- 8.1 yr)
      with symptoms of asthma and an abnormal methacholine challenge test (cases) were
      compared with 92 age- and smoking-history-matched subjects, who denied symptoms
      and had normal methacholine challenge tests (controls). The age of onset of
      wheezing symptoms for the cases was 49.0 +/- 15.7 yr. Serum IgE reactivity to the
      aeroallergens Der P 1 and 2, cat, ragweed, and mouse was compared in cases and
      controls. Cases were more likely to be sensitized to cat allergen (23.9% versus
      4.4%, p < 0.001) than were controls. Prevalences of sensitization to Der p 1, Der
      p 2, ragweed, and mouse were low and similar in the two groups. In Study B, 33
      cases who developed new onset airway hyperresponsiveness on methacholine
      challenge testing were compared with 66 age-matched controls who maintained
      normal methacholine challenge tests. Cases had a higher prevalence of serum IgE
      reactivity to cat allergen (18.2% versus 6.1%, p = 0.059) and Der p 2 (21.2%
      versus 10.6%, p = 0.153) measured in serum obtained 3 yr before the development
      of airway hyperresponsiveness. These results suggest that in older men,
      sensitization to cat allergen is associated with asthma and that sensitization
      predates airway hyperresponsiveness to methacholine.

PMID- 9230722
TI  - Systemic corticosteriod rapidly reverses bronchodilator subsensitivity induced by
      formoterol in asthmatic patients.
AB  - There is evidence that downregulation and desensitization of airway beta 2
      adrenoceptors (beta 2-AR) develops after continuous exposure to long-acting beta
      2-agonists such as formoterol and salmeterol. To investigate the facilitatory
      effects of acute administration of systemic corticosteroid on bronchodilator
      subsensitivity, as might occur in the setting of acute asthma, 12 subjects with
      moderately severe asthma, with a mean FEV1 of 66% predicted, of whom were all
      receiving inhaled corticosteriod, were randomized to receive either inhaled
      placebo (PL) or inhaled formoterol (FM) 24 micrograms twice daily for 4 wk in a
      double-blind crossover study. Subjects were also genotyped in terms of beta 2-Ar
      polymorphism at loci 16 and 27. A dose-response curve (DRC) and duration-time
      profile for FM (12 to 108 micrograms) was produced 1 h after administration of
      placebo tablets and after injection at 3 wk, and 1 h after administration of oral
      prednisolone, 50 mg, and intravenous hydrocortisone, 200 mg, at 4 wk. Comparisons
      between treatments were made with area-under-curve (AUC) measurements as the
      change from baseline. There was a significant rightward shift in the DRC after FM
      as opposed to placebo for delta FEV1 (as AUC, L.h): 2.51 versus 4.22 (95% CI:
      0.54 to 2.89; p = 0.01) and delta FEF25-75 (as AUC, L x 10(3)): 11.30 versus
      19.94 (95% CI: 2.12 to 15.12; p = 0.01). This was significantly reversed by
      steroid (S) for FEV1 (FM versus FM+5): 2.51 versus 3.57 (95% CI: 0.11 to 2.27; p
      = 0.03) and for FEF25-75: 11.30 versus 18.47 (95% CI: 2.52 to 11.70; p = 0.005).
      Lymphocyte beta 2-AR density (log Bmax; fmol/10(6) cells) showed significant
      upregulation 3 h after steroid (FM+5 versus FM): 0.34 versus 0.24 (95% CI: 0.02
      to 0.18; p = 0.01). For heart-rate response (as AUC, beats), there was
      subsensitivity with FM versus PL: 2,700 versus 5,200 (95% CI: 40 to 5,000; p <
      0.001), and this was reversed by steroid (FM+5 versus FM): 9,600 versus 2,700
      (95% CI: 4,900 to 8,800; p < 0.001). This reversal by systemic corticosteroid
      appears to be generally independent of beta 2-AR polymorphism at loci 16 and 27.
      In conclusion, we have demonstrated that bronchodilator subsensitivity occurs
      after regular inhaled FM in asthmatic patients, and is rapidly reversed by
      systemic corticosteroid. Thus, in acute asthma, systemic corticosteroid should be
      administered a soon as possible, in order to restore normal airway beta 2-AR
      sensitivity, particularly in patients who are receiving regular long-acting beta
      2-agonists.

PMID- 9230723
TI  - Diesel exhaust particles enhance antigen-induced airway inflammation and local
      cytokine expression in mice.
AB  - Previous experimental studies have suggested that nasal instillation of diesel
      exhaust particles (DEP) can enhance nasal IgE response and cytokine production.
      However, there is no experimental evidence for the relation of DEP to allergic
      asthma. We investigated the effects of DEP inoculated intratracheally on antigen
      induced airway inflammation, local expression of cytokine proteins, and antigen
      specific immunoglobulin production in mice. DEP aggravated ovalbumin-induced
      airway inflammation characterized by infiltration of eosinophils and lymphocytes
      and an increase in goblet cells in bronchial epithelium. DEP with antigen
      markedly increased interleukin-5 (IL-5) protein levels in lung tissue and
      bronchoalveolar lavage supernatants compared with either antigen or DEP alone.
      The combination of DEP and antigen induced significant increases in local
      expression of IL-4, granulocyte macrophage-colony stimulating factor (GM-CSF),
      and IL-2, whereas expression of interferon-gamma was not affected. In addition,
      DEP exhibited adjuvant activity for the antigen-specific production of IgG and
      IgE. These results provide the first experimental evidence that DEP can enhance
      the manifestations of allergic asthma. The enhancement may be mediated mainly by
      the increased local expression of IL-5, and also by the modulated expression of
      IL-4, GM-CSF, and IL-2.

PMID- 9230724
TI  - No evidence for effects of family environment on asthma. A retrospective study of
      Norwegian twins.
AB  - The risk of developing asthma contingent upon the co-twins' history of asthma was
      analyzed in a population-based study of 5,864 Norwegian twins. A primary aim was
      to assess the significance of shared environment for the development of asthma
      from infancy through age 25. Retrospective reports were collected when the twins
      were 18 to 25 yr of age. The risk of developing asthma, contingent upon the co
      twin's history of asthma, was estimated using survival analyses, and genetic and
      environmental sources of variation in liability for asthma were analyzed with
      structural equation models. The cumulative incidence of asthma was 6% for males
      and 5.4% for females. The relative risk of developing asthma among twins whose co
      twin had a positive history of asthma compared with those whose co-twin had no
      history of asthma was 17.9 (95% CI, 10.3 to 31.0) for identical, and 2.3 (95% CI,
      1.2 to 4.4) for fraternal twins. Although shared environment encompasses many of
      the exposures that are putative risk factors for asthma in this age range, there
      is no evidence of shared environmental influences for asthma. Rather, 75% of the
      variation in liability for asthma was explained by genetic effects and the
      remaining variation was due to nonshared environmental influences. These results
      suggest that the familial risk for asthma is primarily, genetic.

PMID- 9230725
TI  - Clinical improvement of asthma after anthelminthic treatment in a tropical
      situation.
AB  - Intestinal helminths are among the most common infectious organisms of humans,
      particularly in tropical regions, and can induce the production of large
      quantities of IgE antibody. Part of this response is directed against the
      helminths own antigens, but a polyclonal stimulation also occurs that may
      increase the allergic reactivity toward environmental allergens. The importance
      of this in the symptomatology of asthma in these regions is, however, uncertain.
      In the present study we evaluated the effect of regular anthelminthic treatment
      with albendazol for 1 yr on a group of asthmatic patients in a zone in which
      these parasites are endemic. The number of asthmatic crises, need for maintenance
      therapy with inhaled steroids, and use of inhaled beta 2-agonists were compared
      both with those in the year prior to the study for the treated patients, and with
      those in a group of asthmatic subjects evaluated in parallel, but in whom the
      parasitic infections were not controlled. Significant improvement in all of these
      indicators of clinical status occurred in the treated group, not only for the
      period of anthelminth administration, but also for the year following. However,
      after 2 yr without treatment, the severity of asthma reverted to the initial
      state. No significant changes were observed in the control group over the entire
      period of evaluation. At the beginning of the study, the patients' pulmonary
      function was below the levels predicted for normal individuals, but this was not
      changed by the anthelminthic treatment. The patients' total serum IgE levels,
      which were elevated at the beginning of the study, were significantly diminished
      by the anthelminth administration, as were the specific IgE antibody levels and
      positivity in skin tests for immediate hypersensitivity to the common
      environmental allergen Dermatophagoides sp. However, the specific response to
      Ascaris lumbricoides, a common helminth in the area, was maintained despite
      treatment. These results indicate that intestinal helminthic infections can
      contribute to the clinical symptoms of asthma in an endemic situation. This may
      occur via a direct response to the parasite and/or a nonspecific potentiation of
      allergic reactivity to environmental allergens.

PMID- 9230726
TI  - Reliability of inspiratory capacity for estimating end-expiratory lung volume
      changes during exercise in patients with chronic obstructive pulmonary disease.
AB  - The inspiratory capacity (IC) maneuver is increasingly used to monitor exercise
      induced dynamic hyperinflation in patients with COPD. However, the reliability of
      this method in patients with COPD exercising to symptom limitation has not been
      systematically studied and presented. The purpose of the present study was
      therefore to evaluate the reliability of the IC maneuver in assessing changes in
      end-expiratory lung volume (EELV) by assessing the pressure developed during IC
      maneuvers, in patients with COPD during incremental bicycle exercise to
      exhaustion. Fifteen patients with stable COPD performed bicycle exercise to
      symptom limitation. During the experiment, the patients performed IC efforts
      during resting breathing and at the end of each exercise work load. Esophageal
      pressure (Pes) measured at peak inspired volume plateau (zero flow) was -13.5 +/-
      1.9 and -13.4 +/- 1.9 cm H2O (p = 0.79) during IC maneuvers at resting breathing
      and during the final exercise work load, respectively. When the Pes values at the
      peak inspired volume plateau during IC efforts at each exercise level were
      expressed as a percentage of those during resting breathing, the great majority
      of the ratios were above 90% with the lowest at 84%, and these ratios were
      independent of exercise intensity. Despite a constant Pes during IC, there was a
      progressive decrease in IC with increasing exercise work load in most patients,
      suggesting an increase in EELV. At the highest exercise work load achieved, delta
      EELV calculated as the decrease in IC was 0.26 +/- 0.06 L (p < 0.001). We
      conclude that repeated IC maneuver is a simple and reliable method for estimating
      EELV changes during exercise to exhaustion in patients with COPD.

PMID- 9230727
TI  - Thoracoscopic lung volume reduction surgery reduces dyspnea and improves exercise
      capacity in patients with emphysema.
AB  - Improved ventilation and exercise capacity follows thoracoscopic lung volume
      reduction surgery (TLVRS) in patients with severe emphysema. This improvement
      could be related to changes in inspiratory and expiratory flows following
      surgery, with consequent improvement in dyspnea indices. Changes in
      inspiratory/expiratory flows at rest and exercise and their relation to
      subjective improvement in dyspnea after TLVRS are not well known. We studied 25
      patients with severe emphysema who underwent unilateral TLVRS performed in well
      defined zones with decreased perfusion in nuclear medicine lung scans. Early
      follow-up after surgery (4.2 +/- 0.8 mo) showed significant improvements in
      exercise tolerance: The distance covered over a 6 min walk test increased from
      934 +/- 297 to 1,071 +/- 241 ft (p = 0.01). Exercise tolerance using a bicycle
      ergometer showed increased exercise endurance from 4.43 +/- 1.7 to 5.71 +/- 1.8
      min (p < 0.001). The maximum workload tolerated increased from 37 +/- 19 to 52 +/
      21 W (p < 0.01) and VO2 max changed from 9.7 +/- 2 to 11.8 +/- 3 (ml.kg)/min (p
      < 0.01). This increment was achieved by generating significantly larger minute
      ventilation (VE), from 24 +/- 11 to 29 +/- 10 L/min, reached through larger tidal
      volumes (increasing from 951 +/- 330 to 1,145 +/- 367 ml), while maintaining the
      same maximum respiratory rates. Increased VE was also accompanied by significant
      increases in both average inspiratory and expiratory flows measured during
      exercise: from 0.89 +/- 0.41 L/s to 1.06 +/- 0.08 L/s, and from 0.77 +/- 0.37 to
      0.90 +/- 0.32 L/s respectively (p < 0.01). The parallel increment in flows
      resulted in constant T1/Ttot relationship. These functional changes correlated
      with increased inspiratory flows at rest measured with pulmonary function tests
      (forced inspiratory volume in one s [FIV1], expiratory flows [FVC, FEV1], and
      increased maximum voluntary ventilation [MVV]) following the surgically induced
      reduction in residual volume (RV). These objective changes occurred parallel to
      improved dyspnea indices. The Baseline Focal Score was 3.36 +/- 1.47 and the
      Transition Focal Score was 6.12 +/- 0.7. The objectively measured variables at
      rest that best correlated with subjective improvement in dyspnea were the change
      in MVV, change in resting arterial PaO2, and change in FEV1 following TLVRS.
      Exercise variables did not have significant correlation with subjective markers
      indicating improvement in dyspnea, with the exception of the change in Dyspneic
      Index [(VE/MVV)100] at maximum exercise.

PMID- 9230728
TI  - Atopy, asthma, and emphysema in patients with severe alpha-1-antitrypysin
      deficiency.
AB  - Bronchial asthma is characterized by episodic airway obstruction and associated
      with wheezing, a bronchodilator response, an elevation in total serum IgE, and
      atopy. To determine whether asthma is more common in subjects with severe alpha 1
      antitrypsin deficiency (alpha 1-ATD) and airway obstruction, we compared 38
      patients who had this condition (Group 1) with 22 control patients with chronic
      obstructive pulmonary disease (COPD) (Group 2) and with five subjects with alpha
      1-ATD and normal spirometry (Group 3). Subjects were evaluated with a symptom
      questionnaire, pulmonary function testing, intradermal allergen testing, and
      serum IgE measurement. Self-reported wheezing was a common symptom in all patient
      groups, but attacks of wheezing with dyspnea were significantly more common in
      Group 1. Of those patients with airway obstruction, more than 50% showed a
      bronchodilator response whether suffering from alpha 1-ATD or not. Atopy was more
      common in Group 1 than in Group 2 (48% versus 27%). Mean serum IgE for all groups
      was similar but significantly greater in patients with atopy. We estimated the
      prevalence of asthma in the study groups on the basis of the criteria of attacks
      of wheezing, reversible airway obstruction, atopy, and that increased IgE. The
      proportion of patients with asthma in Group 1 was significantly greater than that
      in Group 2 (22% versus 5%, p < 0.05). Our study shows that with control for the
      degree of airway obstruction, asthma, as defined, is more common in patients with
      alpha 1-ATD than in those without it. We suggest that a lack of alpha 1-AT in
      airways increases the propensity to develop asthma.

PMID- 9230729
TI  - Site of pulmonary vasodilation by inhaled nitric oxide in microembolic lung
      injury.
AB  - We investigated the site of pulmonary vasodilation and associated effects on gas
      exchange in response to inhaled NO in acute microembolic lung injury. Pulmonary
      arterial (Ppa) and effective capillary (Pc') pressures versus cardiac output (Q)
      plots were generated in anesthetized dogs before and after, successively, (1)
      embolization with 100 microns glass beads, (2) administration of either a placebo
      (n = 5) or 80 ppm inhaled NO followed by cyclooxygenase inhibition by aspirin 1 g
      given intravenously and again 80 ppm inhaled NO (n = 8). Pc' was estimated from
      the pressure decay curve after pulmonary artery balloon occlusion. Embolism
      increased pulmonary vascular resistance, with a slight decrease in its
      precapillary component, from 77 to 66%. NO decreased Ppa at the highest levels of
      Q, and aspirin increased Ppa at all levels of Q. Neither NO nor aspirin affected
      Pc'/Q plots or pulmonary shunt. We conclude that pulmonary vascular resistance in
      microembolic lung injury increases at the periphery of the pulmonary arterial
      tree, with partial reversibility by inhaled NO and by endogenous products of the
      cyclooxygenase pathway upstream from the site of effective capillary resistance.
      Reduced pulmonary vascular tone does not improve gas exchange in this model of
      acute lung injury.

PMID- 9230730
TI  - Inhomogeneities of ventilation and the diffusing capacity to perfusion in various
      chronic lung diseases.
AB  - Although impairment of gas exchange caused by ventilation-perfusion (VA/Q)
      mismatch has been extensively analyzed, there have been no systematic studies
      focused on determining the distributions of diffusion properties in dose
      connection with those of VA/Q. We attempted to clarify the simultaneous
      distributions of VA/Q and diffusion capacity to perfusion (D/Q) in patients with
      idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease
      (COPD). To assess pathologic determinants causing functional abnormalities, we
      compared VA/Q and D/Q distributions with the findings on high-resolution computed
      tomography. O2, CO2, and CO together with six foreign inert gases were used as
      indicator gases. We transformed the measured data on indicator gases in arterial
      blood into a continuous distribution of Q in the VA/Q-D/Q field. In IPF, active
      alveolitis or acinitis played a major role in producing low D/Q regions impeding
      gas exchange via a diffusion limitation, whereas extensive fibrosis with minimal
      inflammation accounted for low D/Q as well as low VA/Q regions. In COPD, no
      regions with low D/Q ratios were observed, but an abnormality in the VA/Q
      distribution with low or high VA/Q ratios was identified. Emphysematous lesions
      produced high VA/Q regions, whereas peripheral airway involvement yielded low
      VA/Q regions. These findings suggest that hypoxemia in patients with IPF is
      caused by inhomogeneous distributions of D/Q in combination with those of VA/Q.
      Hypoxemia in patients with COPD is attributable primarily to inhomogeneities in
      VA/Q rather than in D/Q distributions.

PMID- 9230731
TI  - Characterization of platelet-activating factor acetylhydrolase in human
      bronchoalveolar lavage.
AB  - Platelet-activating factor (PAF) is a mediator produced in human airways during
      acute and chronic inflammatory lung diseases. The levels of PAF are regulated by
      acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine
      whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was
      obtained from normal donors (n = 18) and from adult patients with mild bronchial
      asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently
      found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory
      phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is
      inhibited as much as 95% by exposure to an oxygen radical-generating system
      (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number
      of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH
      both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF
      alpha) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 +/-
      0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in
      normal donors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity
      in patients with lung fibrosis (6.13 +/- 0.81 pmol/min) is higher than that found
      in normal donors (p < 0.01). The variations in BAL-AH activity in patients with
      bronchial asthma or lung fibrosis are due to a reduction and to an increase,
      respectively, in the number of active molecules rather than to changes in enzyme
      affinity. These data demonstrate that human BAL fluid contains an extracellular
      AH activity that inactivates PAF released in the airways. BAL-AH is secreted by
      alveolar macrophages and is highly sensitive to oxygen radical-induced damage.
      The secretion and inactivation of BAL-AH may influence the levels of this enzyme
      in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately,
      regulate the proinflammatory activities of PAF in these disorders.

PMID- 9230732
TI  - Clinical predictors of mortality from asbestosis in the North American Insulator
      Cohort, 1981 to 1991.
AB  - Recorded mortality from asbestosis has increased markedly in the United States in
      recent decades, from 0.49 to 3.06 per million persons between 1970 and 1990.
      Although asbestosis is generally considered to be a slowly progressive disorder,
      little is known about how clinical and exposure parameters among individuals with
      asbestosis quantitatively predict subsequent risk of death from asbestosis. We
      followed 2,609 insulators from the North American insulator cohort 10 yr to
      determine cause of death and to relate clinical findings to risk of death. This
      group had undergone clinical and radiologic examination between 1981 and 1983 in
      19 cities in the United States. Seventy-four (11.0%) of 674 deaths during the
      subsequent 10 yr were due to asbestosis, according to the best clinical and
      radiologic evidence available at the time of death. The 10 yr risk of death
      (expressed as a percentage) due to asbestosis rose sharply with increasing
      interstitial fibrosis as identified on the baseline chest X-ray, from 0.9% to
      2.4%, 10.8%, and 35.4% for International Labor Office (ILO) profusion categories
      0, 1, 2, and 3, respectively. Dyspnea, a low FVC, and/or physical examination
      findings typical of interstitial fibrosis (rales, clubbing, or cyanosis) raised
      the risk of subsequent death from asbestosis by 2- to 6-fold. The effect of
      cigarette smoking on risk of death from asbestosis was small and disappeared
      after adjustment for ILO profusion score.

PMID- 9230733
TI  - Pulmonary epithelial cell injury and alveolar-capillary permeability in
      berylliosis.
AB  - Inhaled beryllium induces specific sensitization and nonspecific effects leading
      to chronic beryllium disease (CBD). It is not known whether beryllium induces
      epithelial cell injury and increases alveolar-capillary leak. We hypothesize that
      lung injury is an early event in this disease and that markers of lung injury
      reflect severity of CBD. We measured serum and bronchoalveolar lavage fluid
      (BALF) KL-6 level, a marker of epithelial cell injury, and BALF/serum albumin, a
      marker of alveolar-capillary permeability, in 26 patients with CBD, 15 beryllium
      sensitized subjects without disease (BeS), and 32 control subjects (Ctrl). We
      examined the association of these markers, BAL cellularity, pulmonary function,
      gas exchange, serum angiotensin-converting enzyme, chest radiograph, the effects
      of glucocorticoid therapy, and clinical course. BALF/serum albumin and serum KL-6
      increased in CBD and were discriminative markers for CBD. BALF KL-6 and
      BALF/serum albumin reflected mainly lung cellular and granulomatous inflammation.
      Serum KL-6, like and BALF KL-6, was associated with permeability change and
      reflected functional and radiologic abnormalities. Serum KL-6 detected early lung
      injury in BeS. Epithelial injury and permeability changes occur early in CBD,
      indicating disease severity. Monitoring of these events with serum KL-6 may be
      useful for management of CBD.

PMID- 9230734
TI  - The relationship between maximal expiratory flow and increases of maximal
      exercise capacity with exercise training.
AB  - We previously reported that patients with mild to moderate airflow limitation
      have a lower exercise capacity than age-matched controls with normal lung
      function, but the mechanism of this reduction remains unclear (1). Although the
      reduced exercise capacity appeared consistent with deconditioning, the patients
      had altered breathing mechanics during exercise, which raised the possibility
      that the reduced exercise capacity and the altered breathing mechanics may have
      been causally related. Reversal of reduced exercise capacity by an adequate
      exercise training program is generally accepted as evidence of deconditioning as
      the cause of the reduced exercise capacity. We studied 11 asymptomatic volunteer
      subjects (58 +/- 8 yr of age [mean +/- SD]) selected to have a range of lung
      function (FEV1 from 61 to 114% predicted, with a mean of 90 +/- 18% predicted).
      Only one subject had an FEV1 of less than 70% predicted. Gas exchange and lung
      mechanics were measured during both steady-state and maximal exercise before and
      after training for 30 min/d on 3 d/wk for 10 wk, beginning at the steady-state
      workload previously determined to be the maximum steady-state exercise level that
      subjects could sustain for 30 min without exceeding 90% of their observed maximal
      heart rate (HR). The training workload was increased if the subject's HR
      decreased during the training period. After 10 wk, subjects performed another
      steady-state exercise test at the initial pretraining level, and another maximal
      exercise test. HR decreased significantly between the first and second steady
      state exercise tests (p < 0.05), and maximal oxygen uptake (VO2max) and
      ventilation increased significantly (p < 0.05) during the incremental test,
      indicating a training effect. However, the training effect did not occur in all
      subjects. Relationships between exercise parameters and lung function were
      examined by regression against FEV1 expressed as percent predicted. There was a
      significant positive correlation between VO2max percent predicted and FEV1
      percent predicted (p < 0.02), and a negative correlation between FEV1 and end
      expiratory lung volume (EELV) at maximal exercise (p < 0.03). There was no
      significant correlation between FEV1 and maximal HR achieved during exercise;
      moreover, all subjects achieved a maximal HR in excess of 80% predicted,
      suggesting a cardiovascular limitation to exercise. These data do not support the
      hypothesis that the lower initial VO2max in the subjects with a reduced FEV1 was
      due to deconditioning. Although increased EELV at maximal exercise, reduced
      VO2max and a reduced VO2max response with training are all statistically
      associated with a reduced FEV1, there is no direct evidence of causality.

PMID- 9230735
TI  - Efficacy of combined inspiratory intercostal and expiratory muscle pacing to
      maintain artificial ventilation.
AB  - Many patients with ventilator-dependent quadriplegia have coincident phrenic
      nerve injury and therefore cannot be offered phrenic nerve pacing. The purpose of
      this study was to assess the utility of combined inspiratory intercostal and
      expiratory muscle pacing to provide complete ventilatory support. Studies were
      performed in 15 anesthetized dogs. An electrode was positioned on the epidural
      surface of the upper thoracic spinal cord to activate the inspiratory intercostal
      muscles; a separate electrode was positioned on the epidural surface of the lower
      thoracic spinal cord to activate the expiratory muscles. In an attempt to
      replicate the effects of inspiratory intercostal pacing alone in humans, stimulus
      parameters during upper thoracic spinal cord stimulation were adjusted to provide
      suboptimal levels of ventilation (end-tidal PCO2 of 55 to 60 mm Hg). Expiratory
      muscle activation was triggered electrically by the inspiratory signal with a 4.2
      s delay resulting in alternate inspiratory and expiratory muscle pacing at a
      combined rate of 14 breaths/min. Combined pacing was maintained for an arbitrary
      period of 3 h. Initial intercostal muscle pacing alone resulted in an end-tidal
      PCO2 of 57.1 +/- 1.1 mm Hg. After the addition of expiratory muscle pacing, end
      tidal PCO2 fell to 36.3 +/- 1.2 mm Hg. Tidal volume during both inspiratory and
      expiratory muscle pacing and end-tidal PCO2 remained stable throughout the study
      period. Our results suggest that combined alternate inspiratory and expiratory
      muscle pacing may be a viable alternative method of artificial ventilation in
      ventilator-dependent quadriplegic patients.

PMID- 9230736
TI  - Upper airway anesthesia reduces phasic genioglossus activity during sleep apnea.
AB  - We hypothesize that stimulation of upper-airway mechanoreceptors during
      obstructive apnea augments upper airway muscle activity. If so, upper-airway
      anesthesia (UAA) should reduce mechanoreceptor output and therefore upper-airway
      muscle activity. To test this hypothesis, we studied the effect of UAA on the
      relationship between the phasic activity of the moving-time average (MTA) of the
      genioglossus electromyogram (EMG-GG) and the esophageal pressure deflection (DP)
      during obstructive apneas in non-rapid-eye-movement (NREM) sleep in a group of
      six men with severe sleep apnea. Before UAA, the phasic EMG-GG was linearly
      related to the deflections in esophageal pressure (DP) during the last three
      occluded breaths (both progressively increased). After UAA, the mean ratio of EMG
      GG to DP decreased to 23% of the control value, from 0.17 +/- 0.04 to 0.04 +/-
      0.01 (mean +/- SEM) arbitrary units/cm H2O (p < 0.05). The mean slope of the EMG
      GG-versus-DP regression lines also decreased to 23% of the control value, from
      0.22 +/- 0.03 to 0.05 +/- 0.01 arbitrary units/ cm H2O (p < 0.01). These findings
      suggest that stimulation of upper-airway mechanoreceptors during obstructive
      apnea in NREM sleep augments phasic genioglossus activity.

PMID- 9230737
TI  - Relationship between chronic hypercapnia and inspiratory-muscle weakness in
      myotonic dystrophy.
AB  - We studied 134 patients with Steinert's myotonic dystrophy (MD) in order to
      determine the prevalence of chronic hypercapnia, the level of muscle weakness and
      forced expiratory volume at which hypercapnic respiratory failure is likely to
      occur, and how clinical assessment might help predict hypercapnic respiratory
      failure. Subjects were divided into five classes with a muscular disability
      rating scale (MDRS): 0 = no clinical impairment (n = 9), I = minimal signs of
      impairment (n = 11), II = distal weakness (n = 41), III = moderate proximal
      weakness (n = 62), and IV = nonambulatory (n = 11). The prevalence of hypercapnia
      (PaCO2 > or = 43 mm Hg) was found to be 0%, 27%, 29%, 45% and 55% for MDRS 0 to
      4, respectively (p = 0.03). A multiple regression analysis limited to clinical
      data showed that daytime hypersomnolence was a significant cofactor with the MDRS
      (p = 0.01) in predicting PaCO2 (r = 0.40). Among respiratory parameters, FVC,
      respiratory muscle strength (RMS), and maximal inspiratory pressure against
      occluded airways (PImax) were found to be predictors of nearly equal strength,
      explaining 16%, 15%, and 14% of the PaCO2 variance, respectively. In multiple
      regression analysis, sex, daytime sleepiness, and the expected/observed FVC ratio
      for a given RMS were found to be significant cofactors with PImax in predicting
      PaCO2 (r = 0.51). It is concluded that respiratory insufficiency should be
      suspected in MD patients with proximal weakness or daytime sleepiness. The
      likelihood of hypercapnia also increases with volume restriction and respiratory
      muscle weakness. Our study suggests that the combination of inspiratory muscle
      weakness and loading plays a predominant role in the pathogenesis of chronic
      alveolar hypoventilation in MD patients. The occurrence of daytime
      hypersomnolence suggests that other factors, such as low central ventilatory
      drive or sleep apnea, might play an additional role.

PMID- 9230738
TI  - Increased superoxide production during fatigue in the perfused rat diaphragm.
AB  - This study test the hypothesis that a temporal relationship exists between the
      production of superoxide anion (O2-) and the contractile activity of perfused rat
      diaphragm. O2- levels were determined minute to minute by measuring the reduction
      of cytochrome c in the perfusate as the diaphragms were subjected to various
      levels of contractile activity. After equilibrating at low contractile rates (one
      500 ms 80 Hz train/min), diaphragms were fatigued by increasing their contractile
      activity for 5 min (one 500 ms 80 Hz train/s) and then allowed to recover for 30
      min (one 500 ms 80 Hz train/min). During equilibration, diaphragms did not
      produce O2- above the background level measured in the presence of superoxide
      dismutase (SOD). Within the first minute of fatigue-inducing stimulation,
      however, the rate of O2- production increased to 0.70 +/- 0.17 nmol/min and
      remained elevated until the recovery period when production returned towards
      baseline. SOD blocked this stimulation-related increase of O2-. Tension (+/-SOD)
      fell to 12% of the control value during the fatigue-inducing stimulation. During
      recovery the contractile response returned to 51% of control, indicating long
      lasting effects on the contractile machinery. SOD did not limit fatigue or
      improve recovery, probably because it is a large protein that cannot cross cell
      membranes and protect the cells by scavenging O2- at its site of production.

PMID- 9230739
TI  - Respiratory response to CO2 during pressure-support ventilation in conscious
      normal humans.
AB  - The respiratory response to CO2 during pressure-support ventilation (PSV) was
      studied in 16 conscious normal humans. The subjects breathed through a mouthpiece
      connected to a ventilator in PSV mode, with pressure set to the highest
      comfortable level for each subject (10.1 +/- 0.6 cm H2O, mean +/- SE). Compared
      with breathing spontaneously through the ventilator (CPAP mode with zero positive
      end-expiratory pressure), with PSV, tidal volume (VT) increased significantly
      (1.16 +/- 0.1 versus 0.85 +/- 0.04 L), whereas breathing frequency (f) remained
      stable (16.0 +/- 0.9 versus 15.6 +/- 1.1 breaths/min). As a result, the subjects
      hyperventilated, decreasing significantly end-tidal PCO2 (PETCO2, 23.5 +/- 1.2
      versus 35.5 +/- 1.1 mm Hg). Fraction of inspired CO2 (FICO2) was then increased
      in steps, and changes in respiratory motor output were quantitated from changes
      in f, VT, ventilation (VI), peak inspiratory flow (Vpeak), and muscle pressure
      (Pmus). Pmus was calculated by the equation of motion, based on respiratory
      system mechanics, which were measured previously by airway occlusion at end
      inspiration, VT, VI, and Pmus increased significantly with increasing PETCO2, and
      the response was detectable even below eupneic levels; f remained relatively
      stable over a wide range of PETCO2 (23 to 45 mm Hg) and increase significantly
      only when PETCO2 approached 50 mm Hg. These results indicate that in conscious
      normal humans during PSV, CO2 responsiveness extends well into hypocapnia and is
      expressed principally as an increase in intensity of respiratory motor output
      with little change in respiratory rate.

PMID- 9230740
TI  - Ventilatory-control abnormalities in familial sleep apnea.
AB  - The role of ventilatory-control abnormalities in predisposing to familial sleep
      disordered breathing (SDB) was assessed in 31 subjects 28 +/- 10 yr of age (mean
      +/- SD). Subjects with (n = 10) and without SDB (n = 12) were recruited from 13
      families having two or more members with SDB. Nine age- and gender-matched
      controls were recruited from families having no member with SDB. Respiratory
      responses to eucapnic hypoxia, and ventilatory and occlusion pressure responses
      to hyperoxic hypercapnia with and without added resistive loads (6.5 cm H2O/L/s),
      were assessed through rebreathing. Age, FEV1, and FVC did not differ among the
      groups. Hypoxic responses (delta VE/delta SaO2) were significantly lower among
      the first-degree relatives of SDB families than among controls (-0.76 +/- 0.47
      L/min/% SaO2, and -1.32 +/- 0.92 L/min/% SaO2, respectively, p < 0.05).
      Respiratory responses to hypercapnia during unloaded conditions were similar
      among the groups. With resistive loading, inspiratory impedance, as measured
      through the relationship of mouth occlusion pressure (P100) to inspiratory flow
      (VT/TI), increased with increasing hypercapnia to a greater extent in members of
      SDB families than in controls (0.169 +/- 0.054 cm H2O/L/min versus 0.122 +/-
      0.051, respectively, p < 0.05). These data suggest that familial SDB may be based
      partly on a familial abnormality in ventilatory control associated with blunting
      of the hypoxic ventilatory response. The greater increase in impedance during
      inspiratory loading in members of affected families also suggests a propensity
      for dynamic airway narrowing.

PMID- 9230741
TI  - Surfactant composition in infants and young children with cystic fibrosis.
AB  - We tested the hypothesis that the composition of bronchial surfactant is normal
      in infants with cystic fibrosis (CF) in the absence of active lung disease but
      that it is altered by lower respiratory tract infection and inflammation. We
      examined the total phospholipid (PL), disaturated phospholipid (DSP), surfactant
      protein-A (SP-A), surfactant protein B (SP-B), and surface activity in
      bronchoalveolar lavage fluid from 27 subjects with CF whose mean age was 22.7 (SD
      14.5) mo. Six infants with stridor served as non-CF controls. Twelve of the
      subjects with CF (CF-I group) had evidence of active pulmonary infection or
      inflammation which was absent in the remaining 15 subjects (CF-NI group). We
      found no differences in the surfactant composition or activity between controls
      and the CF-NI group. In contrast, the DSP/PL ratio was lower in the CF-I subjects
      than in both the CF-NI subjects (p = 0.05) and controls (p < 0.01) suggesting a
      disturbance of surfactant function. SP-A concentrations were higher in the CF-I
      group compared to the other two groups (p < 0.05). These results suggest that the
      bronchial surfactant of infants with CF is altered following lower airway
      infection and inflammation and is not a primary abnormality associated with this
      disorder.

PMID- 9230742
TI  - Revisited physicochemical and transport properties of respiratory mucus in
      genotyped cystic fibrosis patients.
AB  - We investigated the physicochemical and transport properties of sputum samples
      collected in physiotherapy from a well-documented group of 27 cystic fibrosis
      (CF) patients with identified CF genotypes. Sputum samples were characterized ex
      vivo for their water content, surface properties (surface tension and contact
      angle), rheologic properties (viscosity and elastic modulus), and transport
      properties (mucociliary and cough transport). These data were analyzed in
      relation to the clinical status of the patients (FEV1, FVC, Shwachman score,
      Brasfield score, nutritional status), their genotype, and the degree of infection
      of their sputa (leukocyte and Pseudomonas aeruginosa counts). We observed
      negative and significant correlations between mucociliary transport and elastic
      modulus of the patients' sputum (r = -0.63, p < 0.01), and between the cough
      transport and contact angle of the sputum (r = -0.81, p < 0.0001), respectively.
      The P. aeruginosa count was also significantly correlated with the sputum water
      content (r = -0.53, p < 0.02) as well as with the cough transport of the sputum
      (r = -0.62, p < 0.01). In CF patients with a sputum leukocyte count > 2,000/mm3,
      the sputum water content (p < 0.02), FEV1 (p < 0.05) and FVC (p < 0.02) were
      significantly lower than those of CF patients with a leukocyte count < or =
      2,000/mm3. CF patients with a homozygous delta F 508 genotype had significantly
      greater values of sputum water content (p < 0.05), and cough-transport capacity
      (p < 0.05) than did heterozygous patients. No correlation was observed between
      the sputum properties and any of the clinical data. These results suggest that
      the control of infection should be emphasized in CF, since it can directly or
      indirectly modulate the degree of hydration, and therefore the physicochemical
      and transport properties, of airway secretions.

PMID- 9230743
TI  - Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic
      saline alone and in combination with recombinant human deoxyribonuclease I.
AB  - Treatment with recombinant human deoxyribonuclease I (rhDNase) is currently used
      as therapy for cystic fibrosis (CF) lung disease. Hypertonic saline (HS) acts as
      an expectorant promoting mucus secretion and augmenting the volume of sputum. We
      evaluated the individual and combined effects of HS and rhDNase in vitro on the
      viscoelasticity of CF sputum. Sputum samples were collected from nine CF patients
      to use for in vitro testing. Aliquots of CF sputum (0.20 to 0.40 g) were
      subjected to the following protocols: (1) negative control sample without any
      treatment; (2) positive control sample, adding 10% volume of normal saline (0.9%
      NaCl); (3) application of hypertonic saline (HS-3% NaCl); (4) combining
      approximately 100 nM concentration of rhDNase with protocols 2 and 3. The samples
      in protocols 2 through 4 were incubated for 30 min at 37 degrees C. For each
      protocol, CF sputum was analyzed at baseline and at 30 min for spinnability by
      filancemeter and viscoelasticity by magnetic microrheometry. Spinnability
      decreased for the sputum samples that were treated with rhDNase, in combination
      with either HS or normal saline. Treatment with HS alone and combined treatment
      with rhDNase and HS decreased log G* (the principal viscoelasticity index) to the
      same degree. Saline alone and rhDNase in normal saline both increased the
      predicted cough clearability of the sputum; however, the combined treatment with
      rhDNase and hypertonic saline had the best overall effect on cough clearability.
      The change in predicted mucociliary clearability, although greatest after HS, was
      not significant. These in vitro results suggest that combined treatment with
      rhDNase and HS should be evaluated further as a potential mucotropic approach to
      augment the clearance of purulent sputum in CF lung disease.

PMID- 9230744
TI  - Repetitive prenatal glucocorticoids improve lung function and decrease growth in
      preterm lambs.
AB  - We evaluated the effects of multiple fetal exposures to glucocorticoids on
      postnatal lung function and growth. Ewes were randomized to receive 1 to 4 doses
      of 0.5 mg/kg betamethasone or saline placebo at 7 d intervals from 104 d to 118 d
      and at 124 d gestation. All lambs were delivered preterm at 125 d gestation, and
      postnatal lung function was evaluated. There were sequential improvements in
      compliance, ventilation efficiency, and lung volumes for two, three, and four
      doses of betamethasone. The maximal effect was a 150% increase in compliance and
      a 4-fold increase in lung volume after fetal exposure to four doses of
      betamethasone. However, birth weights decreased (15% after one dose, 19% after
      two doses, and 27% after three and four doses). There were no changes in lung to
      body weight ratios, lung dry to wet weight ratios, lung protein to body weight
      ratios, or lung hyaluronan content. Prenatal glucocorticoid exposure also altered
      postnatal cortisol, thyroid, and catecholamine plasma levels. Repetitive 7-d
      interval exposures of fetal lambs to glucocorticoids progressively enhanced
      postnatal lung function and resulted in growth and endocrine abnormalities.

PMID- 9230745
TI  - Resource allocation in neonatal and medical ICUs. Epidemiology and rationing at
      the extremes of life.
AB  - This study compared resource allocation to patients who eventually die in
      neonatal ICUs (NICUs) and adult medical ICUs (MICUs). It was performed via
      retrospective, chart review study at ICUs at the University of Chicago-an inner
      city, tertiary care, academic medical center. All patients were admitted to the
      neonatal, general medical, or coronary ICU during 1 calendar yr. Overall
      mortality in the NICU (66/827; 7.9%) was significantly lower than in the adult
      ICUs (219/1320; 16.5%) (p < 0.001). However, mortality for the smallest newborns
      (< 751 g; 51% mortality) was higher than for the oldest adults (> 54 yr; 30%
      mortality) (p = 0.05). Fifty-six percent (37/66) of all neonates who died in the
      NICU did so within the first 48 hr of life. In contrast, nearly two-thirds
      (134/219) of adult ICU deaths occurred after 48 hours in the ICU (p < 0.02). The
      percentage of ICU bed-days devoted to nonsurviving adults (28.8%) was
      significantly larger than the percentage of NICU bed-days devoted to nonsurviving
      babies (7.8%). Even among babies at greatest risk to die (birth weight < 751 g),
      the percentage of NICU bed-days allocated to nonsurviving infants was less than
      20%. In contrast, for the oldest ICU patients (> 84 yr) this value exceeded 50%,
      for ICU patients > 84 yr old who required mechanical ventilation, the percentage
      of ICU bed-days allocated to nonsurvivors approached 90%. Care for the elderly in
      MICUs involves a far greater proportional expenditure of money toward those who
      will not survive than does care for newborns in NICUs. To the extent that
      allocation decisions are driven by concerns about distributive justice and the
      efficient use of scarce resources, it would be more justifiable to ration
      intensive care for the very old than the very young.

PMID- 9230746
TI  - Respiratory syncytial virus infection in infants is associated with predominant
      Th-2-like response.
AB  - Viral infections have been associated with cellular immune responses and
      production of Th-1 cytokines. Respiratory syncytial virus (RSV), however, induces
      virus-specific IgE, which might be a consequence of a Th-2-like activation. To
      test this hypothesis we quantified interferon-gamma (IFN-gamma) and interleukin-4
      (IL-4) in the supernatant of peripheral blood mononuclear cells cultured for 24
      and 48 h in the presence or absence of phytohemaglutinin and pokeweed mitogen and
      the lymphocyte phenotypes to analyze subsets and their activation markers, from
      15 hospitalized infants during an acute lower respiratory infection caused by RSV
      and 17 healthy control infants from 1 to 15 mo of age. Compared with the control
      infants, those infected with RSV had an increase in the number of B-cells (p <
      0.02) and decreases in both CD8+ T-cells (p < 0.01) and activated CD8+/CD25+
      suppressor/ cytotoxic T-cells (p < 0.007). In RSV-infected infants, IFN-gamma
      production was subtotally suppressed, whereas IL-4 production was decreased to a
      lesser degree, giving significantly (p < 0.001) increased IL-4/IFN-gamma ratio
      compared with that in the control infants. These findings suggest a predominant
      Th-z-like response in RSV-infected infants, which could explain some aspects of
      the immunopathogenesis of RSV infection and the RSV-specific and nonspecific IgE
      antibody responses observed.

PMID- 9230747
TI  - The value of routine microbial investigation in ventilator-associated pneumonia.
AB  - The use of microbiologic investigations in routine clinical practice, their value
      in guiding antibiotic prescription, and their influence on outcome were
      prospectively studied in 113 consecutive adults who developed ventilator
      associated pneumonia (VAP). Blood cultures were performed in 78.7% of cases,
      protected specimen brushing in 95.5%, and bronchoalveolar lavage in only 45.1%.
      No causative agent was identified in 13 episodes (11.5%), and results of
      microbial tests directed a change in therapy in 43 (38.0%). Bronchoscopic results
      revealed inadequate initial selection of antibiotic therapy in 27 cases (23.9%)
      and led to a change in antibiotic treatment. Inadequate initial selection was
      still associated with a significantly greater increase in related mortality than
      adequate initial therapy (37.0% versus 15.4%, p < 0.05), although the change in
      therapy permitted clinical resolution in 17 (62.9%) of these 27 episodes, and 10
      patients were discharged alive. Bronchoscopic results also permitted the
      reduction of the antibiotic spectrum in seven episodes (6.1%). This study
      suggests that in patients with VAP, bronchoscopic results are frequently
      associated with changes in antibiotic therapy. Nevertheless, our findings also
      emphasize the critical importance of an appropriate early antibiotic therapy.

PMID- 9230748
TI  - Risk of tuberculin conversion according to occupation among health care workers
      at a New York City hospital.
AB  - Concern about the risk to health care workers of occupationally acquired
      tuberculosis has resulted in extensive and frequently revised guidelines from the
      Centers for Disease Control and Prevention (CDC). Most recent studies, however,
      have determined that community, rather than occupational, exposure is the more
      significant risk for tuberculin conversion. To assess the relative contribution
      of community versus occupational risk, we reviewed the health records of 1,303
      persons employed from 1991 to 1994 at St. Clare's Hospital in New York City, a
      hospital with a high tuberculosis case-rate. Demographic information included
      age, gender, postal zone of residence, country of birth, and BCG vaccination
      status, while occupations were placed into one of five groups. In multivariate
      analysis, occupation was significantly associated with risk of tuberculin
      conversion, while postal zone of residence was not. The group that included
      housekeeping, laundry, and security personnel and the physician-nurse group had
      the highest conversion rates. After implementation of CDC guidelines, there was a
      significant improvement in the employee tuberculin conversion rate. At our
      hospital, occupation was strongly associated with risk of tuberculin conversion.

PMID- 9230749
TI  - Glass bottle workers exposed to low-dose irritant fumes cough but do not wheeze.
AB  - Workers exposed to irritant fumes experience symptoms both during the acute
      episode and afterwards. High-dose irritant exposure can result in permanent
      asthma, but the effects of chronic low-dose irritant exposure are not known.
      Glass bottle workers are exposed to irritant fumes, and have previously been
      reported to have an excess of symptoms. We designed a study to compare irritant
      exposed glass bottle workers with hospital workers matched for socioeconomic
      group, area of residence, age, sex, smoking habit, and allergic history. Symptoms
      reported, spirometry, flow cytometric indices of lymphocyte activation, and past
      medical and employment histories were compared. We also investigated the
      prevalence of bronchial hyperresponsiveness to inhaled methacholine and the cough
      response after inhalation of citric acid and capsaicin. Glass bottle workers
      showed an excess of upper respiratory tract symptoms, cough, and shortness of
      breath compared with matched hospital control workers. There was a significant
      excess of cough induced by citric acid and capsaicin in the bottle workers.
      However, wheeze, baseline spirometry, flow cytometry, and methacholine challenge
      were not significantly different between the two groups. These findings suggest
      that chronic irritant exposure produces an excess of symptoms and increased cough
      sensitivity but not asthma.

PMID- 9230750
TI  - A systematic evaluation of mechanisms in chronic cough.
AB  - We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is
      present in patients with chronic cough of diverse etiology. We determined the
      frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the
      upper airway, sputum eosinophilia, pulmonary aspiration, and psychological
      symptoms in adults with chronic cough. Consecutive adults (n = 30) presenting to
      a tertiary referral clinic with chronic cough were compared with a group of 20
      asymptomatic adults. Measurements included histamine provocation testing with
      measurement of flow volume curves to determine inspiratory and expiratory airflow
      obstruction; hypertonic saline induced sputum for analysis of eosinophils, mast
      cells and lipid-laden macrophages; and a validated psychological symptom
      questionnaire. Symptomatic rhinitis and gastroesophageal reflux were common
      causes of chronic cough. BHR occurred in seven patients (23%) and in no control
      subjects (p < 0.05). UAHR occurred in 40% of patients with cough and in four
      (20%) control subjects (p > 0.05). Eosinophils were present in the sputum of more
      patients with cough than control subjects (50% versus 19%; p < 0.05). High
      degrees of eosinophilia were present in six patients with cough, including three
      without BHR. No subject had significant lipid-laden macrophages. There was
      greater somatization in patients with chronic cough; ten subjects scored in the
      clinically significant range (p < 0.05). Abnormalities in one or more of these
      tests were 7.67-fold (95% CI 1.83-34.52) more likely to occur in cough patients
      than control subjects. We conclude that chronic cough is a nonspecific symptom
      that is associated with several apparently unrelated mechanisms. These include
      UAHR, somatization, BHR, and eosinophilic bronchitis. UAHR cannot be implicated
      as a single unifying mechanism. These findings emphasize the need to
      systematically evaluate several different causes of cough in patients who present
      with chronic cough.

PMID- 9230751
TI  - Impairment of neural nitric oxide-mediated relaxation after antigen exposure in
      guinea pig airways in vitro.
AB  - Nitric oxide (NO), a neurotransmitter of inhibitory nonadrenergic noncholinergic
      (iNANC) nerves in airways, is a radical with a short half-life, and its function
      may be modified by airway inflammation. To test this hypothesis, we examined
      whether airway allergic inflammation affects iNANC responses mediated by NO in
      guinea pigs in vitro. Animals sensitized with ovalbumin (OA) were challenged with
      0.03% OA (OA group) or saline (saline group) by inhalation on 3 consecutive days.
      On the day after the final challenge, iNANC responses elicited by electrical
      field stimulation (2 to 16 Hz) or relaxation responses to 3-morpholinosydnonimine
      (SIN-1), 10(-8) to 10(-4) M, were obtained in the tracheal strips precontracted
      by histamine (3 x 10(-6) M) in the presence of atropine and propranolol (both 10(
      6) M). The INANC responses of the OA group were significantly attenuated compared
      with those of the saline group (p < 0.05), and the inhibitory effect of a NO
      synthase (NOS) inhibitor, Nm-nitro-L-arginine methyl ester, on the INANC
      responses was abolished in the OA group. SIN-1-induced tracheal smooth muscle
      relaxation was also significantly affected by antigen exposure (p < 0.05), the
      effect of which disappeared in the presence of a NO scavenger, carboxy PTIO (3 x
      10(-6) M). The impairment of the INANC responses after antigen exposure was
      significantly restored by superoxide dismutase (1,000 U/ml), especially at lower
      frequencies. Histochemical demonstration of NADPH-diaphorase-positive nerves
      representing neural NOS density was not different between the two groups. These
      results suggest that allergic airway inflammation impairs neural NO-induced
      relaxation, presumably by inhibiting the access of neural NO to the airway smooth
      muscle.

PMID- 9230752
TI  - Expression of inducible nitric oxide synthase by macrophages in rat lung.
AB  - Nitric oxide (NO) is a short-lived free radical that is secreted by pulmonary
      macrophages (Mo). An inducible isoform of NO synthase (iNOS) catalyses the
      production of NO and is activated by lipopolysaccharide and certain T-helper(h) 1
      cytokines, including interferon-gamma and TNF-alpha. In the present study, iNOS+
      interstitial cells were demonstrated in the alveolar wall of normal Lewis rat
      lung. Enzymatic digests of normal lung showed that approximately one third of
      pulmonary ED1+ interstitial Mo (IM) were iNOS+ and secreted modest amounts of NO
      without ex vivo stimulation, whereas normal alveolar macrophages (AM) were iNOS-
      and showed no basal NO secretion. When incubated with heat-killed Listeria
      monocytogenes (HKL) in vitro, AM secreted larger amounts of NO than did IM.
      Recombinant murine GM-CSF stimulated production of NO by AM but not by IM.
      However, when IM were costimulated with GM-CSF and IFN-gamma, they expressed a
      marked increase in NO production. Intratracheal challenge with HKL yielded
      decreased NO production by IM. We conclude that iNOS+ IM are present in normal
      rat lung, where they regulate the pulmonary cell-mediated immune response to
      antigen.

PMID- 9230753
TI  - Increased vascularity of the bronchial mucosa in mild asthma.
AB  - Airway-wall remodeling leading to thickening of the bronchial wall in asthma has
      been invoked to account for airflow obstruction and increased bronchial
      reactivity to provocative stimuli. Bronchial-wall changes characteristic of
      asthma are thought to include increased vascularity with vasodilatation. The
      contention that inflammatory mediators cause bronchial vasodilatation and that
      growth factors may induce increased vascularity is based on little structural
      evidence. We took bronchoscopic biopsies from the major airways of 12 subjects
      with mild asthma and 11 control subjects, and evaluated bronchial vessel numbers
      and size, using computerized image analysis after staining for type IV collagen
      in vessel walls. The airways of asthmatic subjects were significantly more
      vascular (17.2 +/- 4.2 versus 10.3 +/- 1.9%, p < 0.001), with more vessels (738
      +/- 150 versus 539 +/- 276 vessels/mm2 [mean +/- SD], p < 0.05) than those of the
      controls. There were significantly more asthmatic bronchial than control vessels
      with a cross-sectional area greater than 300 microns2 (19.4 versus 12.7%, p <
      0.05). These findings provide the first confirmatory evidence that bronchial
      biopsies from patients with mild asthma are more vascular than those of normal
      controls, that there are more vessels in asthmatic airways, and that asthmatic
      bronchial vessels are larger than controls.

PMID- 9230754
TI  - Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced
      airway inflammation and hyperresponsiveness.
AB  - Cytokine-induced neutrophil chemoattractant (CINC) is a rat chemokine with potent
      chemoattractant effects on neutrophils. We determined the involvement of CINC in
      ozone-induced airway neutrophilia and bronchial hyperresponsiveness (BHR) in the
      rat. We found a marked increase in lung CINC messenger RNA (mRNA) within 2 h
      after cessation of ozone exposure (1 ppm for 3 h), as measured by Northern blot
      analysis, whereas rats exposed to room air had no detectable CINC mRNA. Ozone
      exposure induced a significant neutrophilia in bronchoalveolar lavage fluid
      (BALF) at 24 h after exposure (air-exposed rats: 4.2 +/- 2.0 x 10(4), versus
      ozone-exposed rats: 16.1 +/- 3.7 x 10(4)); prior treatment with a goat anti-CINC
      antibody (1 mg, intravenously) suppressed the neutrophilia (3.1 +/- 0.9 x 10(4)).
      When administered intratracheally, the antibody (230 micrograms) partially
      inhibited the influx of neutrophils. The increase in bronchial responsiveness to
      acetylcholine observed after ozone exposure was not inhibited by the anti-CINC
      antibody. The anti-CINC antibody (1 mg, intravenously) also inhibited BALF
      neutrophilia induced by exposure to a higher concentration of ozone (3 ppm, 3 h),
      without an effect on BHR. CINC is an important chemokine causing ozone-induced
      neutrophil chemoattraction, but is not involved in the induction of ozone-induced
      BHR. The neutrophil is unlikely to contribute to BHR in this model.

PMID- 9230755
TI  - Matrix metalloproteinase expression and production by alveolar macrophages in
      emphysema.
AB  - The aim of this study was to examine the hypothesis that alveolar macrophages
      represent a significant source of matrix-degrading proteinases in the
      emphysematous lung. Macrophages from bronchoalveolar lavage fluid of 10 patients
      with emphysema and 10 normal volunteers were maintained in vitro for 24 h and
      assessed semiquantitatively for mRNA transcript levels of the matrix
      metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME),
      and interstitial collagenase. Release of these MMPs into the culture medium and
      secretion of neutrophil elastaselike activity was also assessed. Elevated levels
      of mRNA transcripts for gelatinase B (p < 0.0005) and interstitial collagenase (p
      < 0.0005) were observed in macrophages from emphysematous patients. Increased
      collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were
      also measured in conditioned medium from patient macrophages. With gelatinase B,
      complexed forms of the enzyme were secreted by patient but not by control
      macrophages. No difference in transcript levels of gelatinase A or MME was
      observed between patient and control samples, and neither enzyme was detected in
      macrophage-conditioned media from either group. These results directly
      demonstrate that alveolar macrophages from the emphysematous lung produce
      elevated quantities of matrix-degrading enzymes with both elastolytic and
      collagenolytic activities.

PMID- 9230756
TI  - Quantification of pulmonary emphysema from lung computed tomography images.
AB  - A texture-based adaptive multiple feature method (AMFM) for evaluating pulmonary
      parenchyma from computed tomography (CT) images is described. This method
      incorporates multiple statistical and fractal texture features. The AMFM was
      compared to two previously published methods, namely, mean lung density (MLD) and
      the lowest fifth percentile of the histogram (HIST). First, the ability of these
      methods to detect subtle differences in ventral-dorsal lung density gradient in
      the prone normal lung was studied. Second, their abilities to differentiate
      between normal and emphysematous whole lung slices were compared. Finally,
      regional analyses comparing normal and emphysematous regions were performed by
      dividing the lungs. In the CT slices into six equal regions, ventral to dorsal,
      and analyzing each region separately. The results demonstrated that the AMFM
      could separate the ventral from the dorsal one-third of the normal prone lung
      with 89.8% accuracy, compared to an accuracy of 74.6% with the MLD and 64.4% with
      the HIST methods. The normal and emphysematous slices were separated on a global
      basis with 100.0% accuracy using the AMFM as compared to an accuracy of 94.7% and
      97.4% using the MLD and HIST methods, respectively. The regional normal and
      emphysematous tissues were discriminated with an average accuracy of 97.9%,
      89.9%, and 99.1% with the AMFM, MLD, and HIST methods, respectively. The three
      methods and the pulmonary function tests in the normal and emphysema groups were
      poorly correlated. Quantitative texture analysis using adaptive multiple features
      holds promise for the objective noninvasive evaluation of the pulmonary
      parenchyma.

PMID- 9230757
TI  - Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis.
AB  - It has recently been shown that an insertion (I)/deletion (D) polymorphism exists
      in the angiotensin-converting enzyme (ACE) gene, and that this polymorphism
      affects the serum ACE level. There are three genotypes: DD, DI, and II, with the
      ACE level highest in DD, intermediate in DI, and lowest in II. In the present
      investigation of the possible significance of the polymorphism for sarcoidosis, a
      total of 207 patients and 314 normal control subjects were examined. There were
      no significant differences in the I/D ratio and the genotype distribution between
      the two groups, and no significant variation in organ involvement (i.e., eye,
      skin, and heart) was noted among the three genotypes. To determine any prognostic
      influence of the polymorphism, we examined the disappearance ratio of abnormal
      shadow on chest radiography over 3 and 5 yr. No significant difference among the
      three genotypes was observed. New normal ranges of serum ACE level were
      determined for each genotype, and found to be 22% more sensitive overall than the
      conventional normal range and 39% more so for II type, suggesting an advantage
      for diagnosis and assessment of the disease activity of sarcoidosis.

PMID- 9230758
TI  - Effects of neutrophil elastase inhibitor on bleomycin-induced pulmonary fibrosis
      in mice.
AB  - Neutrophils play an important role in the pathogenesis of idiopathic pulmonary
      fibrosis (IPF). To elucidate the possible involvement of neutrophil elastase (NE)
      in pulmonary fibrosis, we investigated the efficacy of a new specific NE
      inhibitor (ONO-5046 Na) in a murine model of human IPF, bleomycin-induced
      pulmonary fibrosis. Bronchoalveolar lavage (BAL) and histopathological analysis
      were performed on bleomycin-treated mice (group A), bleomycin and ONO-5046 Na
      treated mice (group B), and saline control groups at 1, 15, and 29 d after the
      end of bleomycin treatment. At 29 d, multifocal fibrosis was observed in group A,
      whereas no fibrotic regions were observed in group B. Interleukin-1 beta and
      macrophage inflammatory protein-2 mRNA levels in BAL cells on day 1, and platelet
      derived growth factor-A and insulin-like growth factor-1 mRNA levels on days 1
      and 15, were significantly lower in group B than in group A. Thus, we
      demonstrated an inhibitory effect of ONO-5046. Na on pulmonary fibrosis in mice,
      indicating the involvement of NE in the pathogenesis of pulmonary fibrosis. We
      propose that this effect might be related to suppressed expression of particular
      cytokines in alveolar macrophages and that this specific NE inhibitor could be a
      novel therapeutic agent for IPF.

PMID- 9230759
TI  - Erythromycin modulates IL-8 expression in normal and inflamed human bronchial
      epithelial cells.
AB  - Erythromycin (EM) and its 14-member macrolide analogues have attracted attention
      for its effectiveness in a variety of airway diseases, including diffuse
      panbronchiolitis (DPB), sinobronchial syndrome, and chronic sinusitis. However,
      its mechanisms of action remain unelucidated. We evaluated the effects of several
      antibiotics on IL-8 expression by normal and transformed human bronchial
      epithelial cells, an important source of this potent chemokine involved in cell
      recruitment into the airways. EM and clarithromycin (CAM) uniquely suppressed
      mRNA levels as well as the release of IL-8 at the therapeutic and noncytotoxic
      concentrations (% inhibition of IL-8 protein release: 25.0 +/- 5.67% and 37.5 +/-
      8.99%, respectively, at 10(-6) M). The other antimicrobes, including a 16-member
      macrolide josamycin, showed no effect. Bronchial epithelial cells from very
      peripheral airways as well as from main bronchi were obtained from patients with
      chronic airway inflammatory diseases, and EM and CAM inhibited IL-8 release from
      these cells. Among five patients who underwent bronchoscopy before and after
      macrolide treatment, four showed decreased levels of IL-8 expression in airway
      epithelium as assessed by reverse transcription and polymerase chain reaction.
      Our findings showed these 14-member macrolides had inhibitory effect on IL-8
      expression in human bronchial epithelial cells, and this new mode of action may
      have relevance to their clinical effectiveness in airway diseases.

PMID- 9230760
TI  - Intraalveolar expression of tumor necrosis factor-alpha gene during conventional
      and high-frequency ventilation.
AB  - The effects of conventional mechanical ventilation (CMV) and high-frequency
      oscillatory ventilation (HFO) on intraalveolar expression of the tumor necrosis
      factor-alpha (TNF-alpha) gene were studied in surfactant-depleted rabbits. After
      lung lavage with saline, 13 rabbits were administered either CMV (n = 6) or HFO
      (n = 7) for 1 h at an FiO2 of 1.0 and a mean airway pressure of 13 cm H2O. Lung
      lavage was then repeated. The rabbits' RNA was extracted from the lavage cells,
      and mRNA for TNF-alpha was quantitated by reverse-transcription polymerase chain
      reaction using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an internal
      standard. At 1 h of ventilation, PaO2 was slightly lower with CMV than HFO, while
      lavage cell counts and cytology were similar between the two groups. The ratio of
      TNF-alpha mRNA to GAPDH mRNA increased with CMV (control, 0.48 +/- 0.04 [SE]
      versus 1 h, 1.02 +/- 0.14, p < 0.01) but did not change with HFO (0.55 +/- 0.07
      versus 0.73 +/- 0.09). In a separate series of experiments, ten surfactant
      depleted rabbits continued to be ventilated for 4 h either by CMV (n = 5) or HFO
      (n = 5). Conventional mechanical ventilation resulted in a progressive hypoxemia,
      decreased lung compliance, increased number of neutrophils in lung lavage fluid,
      and substantial morphological changes including hyaline membrane formation and
      neutrophil accumulation, whereas HFO was associated with minimal changes in such
      physiological and pathological abnormalities. These results suggest that
      activation of alveolar macrophages and production of proinflammatory cytokines
      may play a pivotal role in the early stage of ventilator-induced lung injury, and
      that ventilator mode (CMV or HFO) substantially modulates macrophage activation
      and hence the degree of lung injury.

PMID- 9230761
TI  - Endothelin-1 production during the acute chest syndrome in sickle cell disease.
AB  - To investigate the role of the endothelial-derived vasoactive mediator endothelin
      (ET-1) in the acute chest syndrome (ACS), we incubated bovine pulmonary artery
      endothelial cells (BPAEC) with red blood cells (equivalent to a hematocrit of
      20%) and/or autologous plasma (1:10 dilution) from two patients during ACS and
      during routine clinic visits. Cellular RNA was analyzed for ET-1 transcripts by
      Northern analysis and ET-1 protein levels in BPAEC supernatants and in plasma
      measured by radioimmunoassay. ET-1 mRNA expression and protein levels increased
      in BPAEC exposed to plasma obtained during ACS; in contrast, exposure to plasma
      obtained during routine clinic visits did not alter BPAEC ET-1 mRNA expression or
      protein levels. Plasma ET-1 level was elevated during ACS, decreased during
      resolution, and remained slightly elevated during routine clinic visits. Plasma
      obtained from one patient 4 d prior to hospitalization for vasoocclusive crisis
      contained the highest ET-1 level and markedly increased BPAEC ET-1 mRNA
      expression and protein levels. In both patients, BPAEC ET-1 mRNA and protein
      expression in vitro and plasma ET-1 levels in vivo correlated with stage of
      disease and occurred in the absence of direct erythrocyte contact in vitro. These
      observations suggest that ET-1 production contributes to development of ACS.

PMID- 9230762
TI  - Use of bronchoalveolar lavage semiquantitative cultures in cystic fibrosis.
AB  - To assess bronchoalveolar lavage (BAL) in adult CF patients with respiratory
      symptoms, we studied BAL fluid (BALF) culture results from 28 bronchoscopies in
      11 patients. Patients were asked to provide sputum for culture. All but two
      patients were receiving antibiotics at the time of bronchoscopy, with 13
      bronchoscopies done on patients who had been receiving antibiotics for more than
      10 d. Gram stain of the BALF was positive in 18 cases. In all but one BALF, >
      10,000 colony-forming units per milliliter (cfu/ml) BALF of one or more pathogens
      was identified. The final case grew Burkholderia cepacia, which was not grown in
      the sputum. In only six cases (21%) were the sputum and BALF culture results the
      same. Prior to 11 bronchoscopies, the sputum was not adequate. The remaining 11
      cases either had different pathogens in the BAL (six cases), or had some but not
      all of the BALF pathogens in the sputum. BALF cultures changed therapy in 13
      (48%) of cases. Semiquantitative culture of BALF was a useful diagnostic tool in
      CF in patients in whom empiric therapy failed.

PMID- 9230763
TI  - Sand aspiration with near-drowning. Radiographic and bronchoscopic findings.
AB  - Sand and foreign-body aspiration may accompany drowning and near-drowning, but
      few details regarding such patients are available in the literature. We report a
      26-yr-old woman who suffered near-drowning after a motor-vehicle accident.
      Initial attempts at ventilation were compromised by increased peak airway
      pressures, which decreased following the removal of large amounts of sand from
      the patient's endotracheal tube. Chest radiographs and computed tomographic (CT)
      scans of the patient obtained upon her arrival in the emergency department
      demonstrated sand bronchograms within the lower lobes of both lungs, and sand
      within the maxillary sinuses and stomach. We present the radiographic,
      bronchoscopic, and microbiologic findings within hours after this patient's
      accident, with a review of the literature and provisional recommendations for the
      management of such patients.

PMID- 9230764
TI  - Cerebral metabolism in sleep apnea. Evaluation by magnetic resonance
      spectroscopy.
AB  - Repeated apneic episodes during sleep may lead to cerebral damage in patients
      with obstructive sleep apnea (OSA). We performed proton magnetic resonance (MR)
      spectroscopic studies to examine cerebral metabolism in patients with OSA. We
      studied 15 healthy subjects and 23 patients with OSA who displayed no anatomical
      abnormalities on MR imaging. The patients were classified into two groups based
      on the results of polysomnography: mild OSA (11 patients) or moderate to severe
      OSA (12 patients). All the subjects were examined with two-dimensional chemical
      shift imaging. The N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cre), and
      Cho/Cre ratios for cerebral cortex and white matter were calculated separately. A
      statistically significant intergroup difference was found for the NAA/Cho ratio
      in cerebral white matter (p < 0.005). This ratio was significantly lower in
      patients with moderate to severe OSA than in patients with mild OSA (p < 0.01)
      and healthy subjects (p < 0.01). Our findings indicate that cerebral metabolic
      changes occur in normal-appearing brain tissue in patients with moderate to
      severe OSA. The findings of a decreased NAA/Cho ratio suggests the presence of
      cerebral damage, probably caused by repeated apneic episodes. Proton MR
      spectroscopy may be useful for evaluating cerebral damage in patients with OSA.

PMID- 9230766
TI  - Effect of inspiratory flow rate on respiratory rate in intubated ventilated
      patients.
AB  - It has previously been demonstrated that in normal subjects using a volume-cycled
      ventilator, increasing inspiratory flow rate increases respiratory rate. We
      undertook the current study to determine (1) whether this effect is also present
      in patients with respiratory disease and (2) whether the effect is independent of
      upper airway receptors. Eight ventilator-dependent patients in the intensive care
      unit were studied. Patients were ventilated in the assist-control mode with the
      back-up rate set at 0.5 breaths/min to ensure that all breaths were patient
      triggered. While tidal volume was held constant, flow was changed from a baseline
      flow of 60 L/min. Trials involved changing flow to either 30 or 90 L/min. There
      was a significant decrease in respiratory rate (-3.4 +/- 0.6 min-1, p < 0.001)
      when flow was decreased from 60 to 30 L/min. There was a significant increase in
      respiratory rate (2.3 +/- 0.8 min-1, p < 0.05) when flow was increased from 60 to
      90 L/min. As a result of the change in respiratory rate, TE (expiratory time)
      showed a variable response to changes in flow rate, with some patients actually
      demonstrating a reduced TE with higher flow rates. No patients experienced the
      increase in TE that would have been predicted without a change in respiratory
      rate. We conclude that in intubated ventilated patients, spontaneous respiratory
      rate is sensitive to inspiratory flow rate. This effect appears to be independent
      of upper airway receptors, since it was observed with a by-passed upper airway.
      The increase in respiratory rate seen at higher flow rates undermines attempts to
      increase TE by increasing flow rates. It may also cause a tendency toward
      respiratory alkalosis.

PMID- 9230765
TI  - Safety of one method of sputum induction in asthmatic subjects.
AB  - To assess the safety of sputum induction in asthmatic subjects, we conducted a
      retrospective review of data from 351 sputum inductions in 78 subjects from our
      institution. The sputum induction protcol consisted of baseline FEV1,
      pretreatment with albuterol 180 micrograms, postbronchodilator spirometry 15 min
      later, the induction procedure itself (inhalation of 3% saline for 20 min), and
      postsputum induction spirometry. We found that sputum induction was usually well
      tolerated, although some subjects developed wheeze and dyspnea. Overall, 11 of
      the 78 subjects (14%) had a fall in FEV1 of > or = 20% from the
      postbronchodilator baseline ("excessive bronchoconstriction") during their first
      sputum induction (range: -20 to -69%); no subject developed refractory
      bronchoconstriction requiring hospitalization or emergency room treatment. Only
      one of the 54 subjects (1.9%) with a baseline prebronchodilator FEV1 > 80% had
      excessive bronchoconstriction, whereas 10 of the 24 subjects (42%) whose baseline
      FEV1 was < or = 80% predicted did so. The change in FEV1 during sputum induction
      was significantly correlated with the baseline prebronchodilator FEV1% predicted,
      the baseline postbronchodilator FEV1% predicted, the PC20 for methacholine, and
      the percentage of eosinophils in induced sputum. We conclude that 180 micrograms
      albuterol does not prevent excessive bronchoconstriction in all asthmatic
      subjects undergoing sputum induction, especially in asthmatic subjects with a low
      baseline FEV1. Pulmonary function should be monitored regularly during sputum
      induction in asthmatic subjects to monitor for excessive bronchoconstriction.

PMID- 9230767
TI  - Nasal inhalation of l-menthol reduces respiratory discomfort associated with
      loaded breathing.
AB  - To test the hypothesis that stimulation of cold receptors in the upper airway may
      alleviate the sensation of respiratory discomfort, we investigated the effects of
      nasal inhalation of l-menthol (a specific stimulant of cold receptors) on the
      respiratory sensation and ventilation during the loaded breathing in 11 normal
      subjects. Subjects were asked to rate their sensation of respiratory discomfort
      using a visual analog scale (VAS) while breathing on a device with a flow
      resistive load (180 cm H2O/L/s) or with an elastic load (75.5 cm H2O/L). The
      effects of inhalation of l-menthol on ventilation and respiratory sensation were
      evaluated by comparing the steady-state values of ventilatory variables and VAS
      scores obtained before, during, and after l-menthol inhalation. In 8 of 11
      subjects inhalation of strawberry-flavored air instead of l-menthol was performed
      during loaded breathing. Both during the flow-resistive loading and the elastic
      loading, inhalation of l-menthol caused a significant reduction in sensation of
      respiratory discomfort (flow-resistive loading: 62 +/- 14 [mean +/- SD] VAS units
      before inhalation versus 36 +/- 16 during inhalation, p < 0.01; elastic loading:
      68 +/- 13 before inhalation versus 55 +/- 17 during inhalation, p < 0.01) without
      a significant change in breathing pattern and ventilation. Comparison of the
      effects between the flow-resistive loading and the elastic loading also revealed
      that the reduction in VAS score was more during the flow-resistive loading than
      during the elastic loading (p < 0.01). Inhalation of strawberry-flavored air
      caused neither changes in VAS score nor changes in breathing pattern and
      ventilation, indicating that olfaction is not a contributing factor in the relief
      of respiratory discomfort. We concluded that stimulation of cold receptors in the
      upper airway with nasal inhalation of l-menthol reduces the sensation of
      respiratory discomfort associated with loaded breathing. This effect is more
      effective during the flow-resistive loading than during the elastic loading.

PMID- 9230768
TI  - Effects of growth and development on lung function. Models for study of childhood
      asthma.

PMID- 9230769
TI  - Pretreatment evaluation of non-small-cell lung cancer. The American Thoracic
      Society and The European Respiratory Society.

PMID- 9230770
TI  - Bronchodilators and acute cardiac death.

PMID- 9230771
TI  - Theoretical basis for improvement following reduction pneumoplasty in emphysema.

PMID- 9230772
TI  - Insomnia in young men and subsequent depression. The Johns Hopkins Precursors
      Study.
AB  - The Johns Hopkins Precursors Study, a long-term prospective study, was used to
      study the relation between self-reported sleep disturbances and subsequent
      clinical depression and psychiatric distress. A total of 1,053 men provided
      information on sleep habits during medical school at The Johns Hopkins University
      (classes of 1948-1964) and have been followed since graduation. During a median
      follow-up period of 34 years (range 1-45), 101 men developed clinical depression
      (cumulative incidence at 40 years, 12.2%), including 13 suicides. In Cox
      proportional hazards analysis adjusted for age at graduation, class year,
      parental history of clinical depression, coffee drinking, and measures of
      temperament, the relative risk of clinical depression was greater in those who
      reported insomnia in medical school (relative risk (RR) 2.0, 95% confidence
      interval (CI) 1.2-3.3) compared with those who did not and greater in those with
      difficulty sleeping under stress in medical school (RR 1.8, 95% CI 1.2-2.7)
      compared with those who did not report difficulty. There were weaker associations
      for those who reported poor quality of sleep (RR 1.6, 95% CI 0.9-2.9) and sleep
      duration of 7 hours or less (RR 1.5, 95% CI 0.9-2.3) with development of clinical
      depression. Similar associations were observed between reports of sleep
      disturbances in medical school and psychiatric distress assessed in 1988 by the
      General Health Questionnaire. These findings suggest that insomnia in young men
      is indicative of a greater risk for subsequent clinical depression and
      psychiatric distress that persists for at least 30 years.

PMID- 9230773
TI  - Temporal trends and factors associated with survival after Pneumocystis carinii
      pneumonia in California, 1983-1992.
AB  - The authors investigated quarterly trends in survival after the diagnosis of
      Pneumocystis carinii pneumonia for 19,607 patients in California in the decade
      from January 1, 1983, through December 31, 1992. Subjects included all cases for
      whom P. carinii pneumonia was the initial (and only) acquired immunodeficiency
      syndrome (AIDS)-defining diagnosis as reported to the California human
      immunodeficiency virus/AIDS surveillance registry. There was a period of rapidly
      improving survival from approximately June 1986 until April 1988, coincident with
      the widespread introduction of antiretroviral therapy (zidovudine) and the
      institution of P. carinii pneumonia prophylaxis (with cotrimoxazole and
      pentamidine). There was no evidence, however, of meaningful improvements in
      survival for these patients after that period. The association of several
      covariates (risk transmission group, gender, race/ethnicity, certainty of P.
      carinii pneumonia diagnosis, age, region of residence, availability of CD4 count,
      and level of CD4 count) were also studied both by proportional hazards regression
      and by recursive partitioning (i.e., tree-based) survival analysis. The
      availability of a CD4 count (regardless of its level) was the single factor most
      strongly associated with survival (median survival 36 months among those with and
      14 months among those without reported CD4 counts, p < 0.05). Data from this
      large, population-based surveillance registry of AIDS in California suggest that,
      despite earlier improvements in survival after the diagnosis of P. carinii
      pneumonia, the long-term survival of these patients remains poor (39% alive 2
      years after diagnosis) and that no improvement in survival has occurred since
      1988.

PMID- 9230774
TI  - Environmental tobacco smoke and breastfeeding duration.
AB  - The effect of smoking on breastfeeding duration was investigated in a population
      based birth cohort study of 1,098 Brazilian infants. There were few losses to
      follow-up (3.2%) in the first 6 months. Maternal smoking was strongly associated
      with breastfeeding duration, even after adjustment for confounding. Compared with
      nonsmokers, mothers smoking 20 or more cigarettes daily presented an odds ratio
      of 1.94 for breastfeeding for less than 6 months. Environmental tobacco smoke was
      also an independent risk factor. After adjustment for maternal smoking and other
      confounders, households where more than 10 cigarettes were smoked daily by
      persons other than the mother presented an odds ratio of 1.48 compared with those
      without smokers. These results remained unchanged after stratification for
      maternal smoking. This is the first report of a possible effect of environmental
      tobacco smoke on breastfeeding duration.

PMID- 9230775
TI  - Use of multivitamin/mineral prenatal supplements: influence on the outcome of
      pregnancy.
AB  - The objective of this study was to examine the association of prenatal
      multivitamin/mineral supplement use during the first and second trimesters of
      pregnancy by low income, urban women in the Camden Study (1985-1995, n = 1,430)
      and preterm delivery (< 37 completed weeks) and infant low birth weight (< 2,500
      g). Prenatal supplement use was corroborated by assay of circulating
      micronutrients at entry to care (no differences) and week 28 gestation (increased
      concentrations of folate and ferritin for supplement users). Compared with women
      who entered care during the first or second trimester but did not use prenatal
      supplements, supplement use starting in the first or second trimester was
      associated with approximately a twofold reduction in risk of preterm delivery.
      After controlling for potential confounding variables, risk of very preterm
      delivery (< 33 weeks' gestation) was reduced more than fourfold for first
      trimester users and approximately twofold when use dated from the second
      trimester. Infant low birth weight and very low birth weight (< 1,500 g) risks
      were also reduced. Risk of low birth weight was reduced approximately twofold
      with supplement use during the first and second trimester. Diminution in risk was
      greater for very low birth weight infants, amounting to a sevenfold reduction in
      risk of very low birth weight with first trimester supplementation and a greater
      than sixfold reduction when supplement use started in the second trimester. Thus,
      in low income, urban women, use of prenatal multivitamin/mineral supplements may
      have the potential to diminish infant morbidity and mortality.

PMID- 9230776
TI  - Hostility and increased risk of mortality and acute myocardial infarction: the
      mediating role of behavioral risk factors.
AB  - Cynical hostility has been associated with increased cardiovascular morbidity and
      mortality; yet few studies have investigated this relation in population-based
      samples, and little is known about underlying mechanisms. This study examined the
      association between hostility, measured by the eight-item Cynical Distrust Scale,
      and risk for all-cause and cardiovascular mortality and incident myocardial
      infarction. Subjects were 2,125 men, ages 42-60 years, from the Kuopio Ischemic
      Heart Disease Risk Factor Study, a longitudinal study of unestablished and
      traditional risk factors for ischemic heart disease, mortality, and other
      outcomes. There were 177 deaths (73 cardiovascular) in 9 years of follow-up. Men
      with hostility scores in the top quartile were at more than twice the risk of all
      cause mortality (relative hazards (RH) 2.30, 95% confidence interval (CI) 1.47
      3.59) and cardiovascular mortality (RH 2.70, 95% CI 1.27-5.76), relative to men
      with scores in the lowest quartile. Among 1,599 men without previous myocardial
      infarction or angina, high scorers also had an increased risk of myocardial
      infarction (RH 2.18, 95% CI 1.01-4.70). Biologic and socioeconomic risk factors,
      social support, and prevalent diseases had minimal impact on these associations,
      whereas adjustments for the behavioral risk factors of smoking, alcohol
      consumption, physical activity, and body mass index substantially weakened the
      relations. Simultaneous risk factor adjustment eliminated the observed
      associations. Results show that high levels of hostility are associated with
      increased risk of all-cause and cause-specific mortality and incident myocardial
      infarction and that these effects are mediated primarily through behavioral risk
      factors.

PMID- 9230777
TI  - Long-term prognosis of women after myocardial infarction. SPRINT Study Group.
      Secondary Prevention Reinfarction Israeli Nifedipine Trial.
AB  - Women sustaining myocardial infarction fare worse than men during
      hospitalization. Reports on long-term survival in women surviving an acute
      myocardial infarction are controversial. The Secondary Prevention Reinfarction
      Israeli Nifedipine Trial (SPRINT) registry includes 5,839 consecutive myocardial
      infarction patients who were hospitalized in 13 coronary care units in Israel
      between 1981 and 1983. The authors examined sex differences in the long-term
      survival of 4,808 hospital survivors (1,120 women and 3,688 men). Women exhibited
      a significantly poorer long-term survival than men. After age adjustment,
      differences between men and women decreased, leaving a survival probability
      difference of 11% at the end of 12 years of follow-up. In a subgroup analysis,
      women exhibited poorer survival than men in a comparison of patients with and
      without periinfarction congestive heart failure or a history of myocardial
      infarction preceding the index infarction. The multivariate adjusted hazard
      ratios associated with female sex in diabetic and nondiabetic patients were 1.46
      and 1.13, respectively. In conclusion, a cumulative survival disadvantage for
      women in comparison with men is still evident after 12 years of follow-up. The
      mortality difference is diminished but not erased after age adjustment or
      multivariate adjustment for confounders. The authors' results are compatible with
      a hypothesis that the main factor underlying the increased long-term mortality in
      women after myocardial infarction, besides older age, is diabetes mellitus.

PMID- 9230778
TI  - Breast cancer clusters in the northeast United States: a geographic analysis.
AB  - High breast cancer mortality rates have been reported in the northeastern part of
      the United States, with recent attention focused on Long Island, New York. In
      this study, the authors investigate whether the high breast cancer mortality is
      evenly spread over the Northeast, in the sense that any observed clusters of
      deaths can be explained by chance alone, or whether there are clusters of
      statistical significance. Demographic data and age-specific breast cancer
      mortality rates for women were obtained for all 244 counties in 11 northeastern
      states and for the District of Columbia for 1988-1992. A recently developed
      spatial scan statistic is used, which searches for clusters of cases without
      specifying their size or location ahead of time, and which tests for their
      statistical significance while adjusting for the multiple testing inherent in
      such a procedure. The basic analysis is adjusted for age, with further analyses
      examining how the results are affected by incorporating race, urbanicity, and
      parity as confounding variables. There is a statistically significant and
      geographically broad cluster of breast cancer deaths in the New York City
      Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4%
      higher mortality rate than the rest of the Northeast. The cluster remains
      significant when race, urbanicity, and/or parity are included as confounding
      variables. Four smaller subclusters within this area are also significant on
      their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p =
      0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p =
      0.0001). The elevated breast cancer mortality on Long Island might be viewed less
      as a unique local phenomenon and more as part of a more general situation
      involving large parts of the New York City-Philadelphia metropolitan area. The
      several known and hypothesized risk factors for which we could not adjust and
      that may explain the detected cluster are most notably age at first birth, age at
      menarche, age at menopause, breastfeeding, genetic mutations, and environmental
      factors.

PMID- 9230779
TI  - Diet and the risk of salivary gland cancer.
AB  - Cancer of the major salivary glands is relatively rare, and little is known about
      its etiology. The only established risk factors are radiation exposure and a
      prior cancer. The role of diet in the development of salivary gland tumors has
      not been addressed previously. The results from a population-based case-control
      study conducted in the greater San Francisco-Monterey Bay area examining the
      association between dietary intake and salivary gland cancer risk are presented.
      Of 199 cases diagnosed with salivary gland tumors between 1989 and 1993, 150
      (75%) were interviewed. Nine cases were subsequently excluded based on review of
      pathology specimens. Of 271 controls identified through random-digit dialing and
      the Health Care Finance Administration files, 191 (70%) were interviewed. Eight
      cases and seven controls who over- or underreported dietary intake were excluded
      from analysis. Vitamin C intake of > 200 mg/day compared with < or = 100 mg/day
      was associated with a 60% decrease in salivary gland cancer risk (odds ratio (OR)
      = 0.40, 95% confidence interval (CI) 0.22-0.70). Inverse associations observed
      for carotene, vitamin E, and fiber from fruits and vegetables were diminished
      when adjusted for vitamin C intake. Fiber from been sources was associated with a
      51% decrease in risk after adjusting for vitamin C intake (OR = 0.49, 95% CI 0.26
      0.92 for > 1.4 g/day compared with < or = 0.4 g/day). Cholesterol intake was
      associated with elevated risk (OR = 1.67, 95% CI 1.2-2.4 for a 10% increase in
      calories from cholesterol). These findings suggest that preventive strategies
      developed for common chronic diseases, such as increased consumption of fruits
      and vegetables and limiting foods high in cholesterol, also may be effective in
      preventing these rare tumors.

PMID- 9230780
TI  - Short-term effects of ambient oxidant exposure on mortality: a combined analysis
      within the APHEA project. Air Pollution and Health: a European Approach.
AB  - The Air Pollution and Health: a European Approach (APHEA) project is a
      coordinated study of the short-term effects of air pollution on mortality and
      hospital admissions using data from 15 European cities, with a wide range of
      geographic, sociodemographic, climatic, and air quality patterns. The objective
      of this paper is to summarize the results of the short-term effects of ambient
      oxidants on daily deaths from all causes (excluding accidents). Within the APHEA
      project, six cities spanning Central and Western Europe provided data on daily
      deaths and NO2 and/or O3 levels. The data were analyzed by each center separately
      following a standardized methodology to ensure comparability of results. Poisson
      autoregressive models allowing for overdispersion were fitted. Fixed effects
      models were used to pool the individual regression coefficients when there was no
      evidence of heterogeneity among the cities and random effects models otherwise.
      Factors possibly correlated with heterogeneity were also investigated.
      Significant positive associations were found between daily deaths and both NO2
      and O3. Increases of 50 micrograms/m3 in NO2 (1-hour maximum) or O3 (1-hour
      maximum) were associated with a 1.3% (95% confidence interval 0.9-1.8) and 2.9%
      (95% confidence interval 1.0-4.9) increase in the daily number of deaths,
      respectively. Stratified analysis of NO2 effects by low and high levels of black
      smoke or O3 showed no significant evidence for an interaction within each city.
      However, there was a tendency for larger effects of NO2 in cities with higher
      levels of black smoke. The pooled estimate for the O3 effect was only slightly
      reduced, whereas the one for NO2 was almost halved (although it remained
      significant) when two pollutant models including black smoke were applied. The
      internal validity (consistency across cities) as well as the external validity
      (similarities with other published studies) of our results on the O3 effect
      support the hypothesis of a causal relation between O3 and all cause daily
      mortality. However, the short-term effects of NO2 on mortality may be confounded
      by other vehicle-derived pollutants. Thus, the issue of independent NO2 effects
      requires additional investigation.

PMID- 9230781
TI  - Cohort mortality study of pulp and paper mill workers in British Columbia,
      Canada.
AB  - The authors studied a cohort of 30,157 male pulp and paper workers in British
      Columbia, Canada. Of these, 20,373 worked in kraft mills only, 5,249 in sulfite
      mills only, and 4,535 in both kraft and sulfite mills. All workers with at least
      1 year of employment on January 1, 1950, or thereafter until December 31, 1992,
      were studied. Standardized mortality ratios (SMRs) were used to compare the
      mortality rates of the cohort with those of the Canadian male population. Ninety
      percent confidence intervals (CIs) for the SMRs were obtained. Cancer risks
      significantly associated with work duration and time from first employment of 15
      years or more were observed: 1) total cohort: pleura (SMR = 3.61, 90% CI 1.42
      7.58); kidney (SMR = 1.69, 90% CI 1.13-2.43); brain (SMR = 1.51, 90% CI 1.03
      2.16); 2) workers in kraft mills only: kidney (SMR = 1.92, 90% CI 1.04-3.26); 3)
      workers in sulfite mills only: Hodgkin's disease (SMR = 4.79, 90% CI 1.29-12.37);
      4) workers ever employed in both kraft and sulfite mills: esophagus (SMR = 1.91,
      90% CI 1.00-3.33). These malignancies have been associated with the following
      known or suspected carcinogens to which pulp and paper workers may have been
      exposed: asbestos (pleura), biocides (kidney), formaldehyde (kidney, brain,
      Hodgkin's disease), hypochlorite (esophagus). A nested case-control study with
      detailed exposure assessment is under way to help determine whether excess risks
      for specific cancers reflect exposure among subsets of workers.

PMID- 9230782
TI  - Logistic regression when the outcome is measured with uncertainty.
AB  - In epidemiologic research, logistic regression is often used to estimate the odds
      of some outcome of interest as a function of predictors. However, in some
      datasets, the outcome of interest is measured with imperfect sensitivity and
      specificity. It is well known that the misclassification induced by such an
      imperfect diagnostic test will lead to biased estimates of the odds ratios and
      their variances. In this paper, the authors show that when the sensitivity and
      specificity of a diagnostic test are known, it is straightforward to incorporate
      this information into the fitting of logistic regression models. An EM algorithm
      that produces unbiased estimates of the odds ratios and their variances is
      described. The resulting odds ratio estimates tend to be farther from the null
      but have greater variance than estimates found by ignoring the imperfections of
      the test. The method can be extended to the situation where the sensitivity and
      specificity differ for different study subjects, i.e., nondifferential
      misclassification. The method is useful even when the sensitivity and specificity
      are not known, as a way to see the degree to which various assumptions about
      sensitivity and specificity affect one's estimates. The method can also be used
      to estimate sensitivity and specificity under certain assumptions or when a
      validation subsample is available. Several examples are provided to compare the
      results of this method with those obtained by standard logistic regression. A SAS
      macro that implements the method is available on the World Wide Web at
      http:@som1.ab.umd.edu/Epidemiology/software.h tml.

PMID- 9230783
TI  - Impaired microcirculation and tissue oxygenation in human cerebral malaria: a
      single photon emission computed tomography and near-infrared spectroscopy study.
AB  - Serial single photon emission computed tomography (SPECT), near-infrared
      spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were
      performed to investigate changes of cerebral perfusion and tissue oxygenation in
      a patient with complicated cerebral malaria that have been acquired in Nigeria.
      On admission to the Neurologic Intensive Care Unit in Innsbruck, Austria, SPECT
      and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen
      saturation, respectively, correlating exactly to the patient's right hemispheric
      localizing signs. In contrast, TCD examinations of the basal cerebral vessels
      revealed normal flow patterns. The patient showed an initial Plasmodium
      falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral
      mefloquine therapy. He was discharged without neurologic symptoms. Follow-up
      SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation
      patterns in both cortical hemispheres. In summary, the presented findings provide
      first evidence that noninvasive SPECT and NIRS may be important diagnostic tools
      in the evaluation of impaired cerebral microcirculation in patients with P.
      falciparum malaria.

PMID- 9230784
TI  - Detection of Trypanosoma cruzi with the polymerase chain reaction and in situ
      hybridization in infected murine cardiac tissue.
AB  - Chagas' disease is caused by the hemoflagellate protozoan Trypanosoma cruzi,
      which is predominantly found in South and Central America and Mexico. Although
      the parasite is present in the United States, confirmed cases of human disease
      are rare. The most serious manifestation of chronic Chagas' disease is a
      progressive inflammatory cardiomyopathy. However, T. cruzi has not been
      consistently demonstrated with histologic techniques in inflammatory cardiac
      lesions. In this study, we used both polymerase chain reaction (PCR)
      amplification of extracted DNA from hematoxylin and eosin-stained tissue
      scrapings, and in situ hybridization to detect the presence of T. cruzi in
      infected murine cardiac tissue sections. Three T. cruzi-specific DNA sequences
      were used: a 122-basepair (bp) sequence localized within the minicircle network
      (MCS), a 188-bp nuclear repetitive sequence (RS), and a 177-bp sequence within
      the open reading frame of a gene coding for a flagellar protein (FPS). We found
      that all three sequences are amplifiable from scrapings of murine cardiac tissue.
      The MCS and RS are detected at 0.167 and 0.24 amastigote DNA equivalents, while
      FPS is barely detected at 0.24 amastigote DNA equivalents. On the other hand, in
      situ hybridization with all three sequences allowed for the detection of T. cruzi
      amastigotes within the tissue. The MCS and FPS, however, consistently yielded a
      more intense signal. These results indicate that PCR and in situ hybridization
      may prove useful in establishing the prevalence of T. cruzi in human chagasic
      cardiomyopathy.

PMID- 9230785
TI  - Chagasic megacolon associated with colon cancer.
AB  - Two cases of chagasic megacolon associated with colon cancer are reported. This
      is the first communication with complete clinical details of this association.
      Our two cases presented tumors (adenocarcinomas) in a nondilated segment of the
      transverse colon. The associated tumor lesions were diagnosed by a barium enema.
      Both patients had a typical clinical epidemiology and history of chagasic
      megacolon.

PMID- 9230786
TI  - Secondary impairment of pancreatic function as a cause of severe malabsorption in
      intestinal giardiasis: a case report.
AB  - We report the case of a 54-year-old male patient hospitalized for diarrhea and
      weight loss (8 kg over the previous three months). At admission, we observed pale
      oral and conjunctival mucosa and peripheral edema of the lower limbs. Stool
      frequency was 8-10 per day. Laboratory data were as follows: hemoglobin, 11 g/dL;
      total proteins, 4.3 g/dL; albumin, 2 g/dL; pseudocholinesterase, 1248 U/L;
      triglycerides, 54 mg/dL; serum cholesterol, 102 mg/dL; calcium, 7.9 mg/dL. Fecal
      fat was 8.2 g/24 hr. Fecal chymotrypsin (FCT) was 2.3 U/g. A duodenal probe was
      performed after administration of intravenous secretin and cerulein stimulation,
      and a contemporaneous mucosal biopsy was taken at the ligament of Treitz.
      Microscopic examination showed numerous Giardia lamblia in the fluid collected.
      Pancreatic enzyme activity in the duodenal fluid showed a severe reduction in
      lipase: 120 U/ml/min (normal value = 600 U/ml/min). Small bowel bacterial
      overgrowth was excluded by microbiologic examination of intestinal fluid. The
      patient was treated with metronidazole, leading to a complete remission of
      symptoms. Immediately after stopping treatment, the FCT was 15.2 U/g. Four months
      after hospitalization, the patient's weight had increased by 11 kg and he was
      asymptomatic; total proteins were 6.7 g/dL; albumin, 3.8 g/dL; triglycerides, 104
      mg/dL; cholesterol, 152 mg/dL; pseudocholinesterase, 3,567 mg/dL; calcium, 10
      mg/dL; steatorrhea was 3.6 g/24 hr and fecal chymotrypsin was 88 U/g. This case
      describes a severe, reversible impairment in pancreatic function leading to
      clinical malabsorption in the presence of Giardia infection.

PMID- 9230787
TI  - Granulomatous amebic encephalitis due to Balamuthia mandrillaris (Leptomyxiidae):
      report of four cases from Mexico.
AB  - In this report, we describe four cases of granulomatous amebic encephalitis
      caused by Balamuthia (Leptomyxid ameba) in four previously healthy Mexican
      patients. All four cases were characterized by focal neurologic signs, increased
      intracranial pressure, and cerebral hyperdense lesions in computed tomography
      scans of the head. These patients underwent craniotomies for evaluation of mass
      lesions for possible brain tumors. Granulomatous chronic inflammatory reaction
      and amebic trophozoites were found in brain biopsies. At autopsy, areas of
      hemorrhagic encephalomalacia were located in both basal frontal lobes, right
      parieto-occipital lobes, and, less often, in the brainstem and cerebellum.
      Angiitis, necrotizing granulomatous encephalitis, and large numbers of amebic
      trophozoites in perivascular spaces were present. Amebic trophozoites were seen
      in the left adrenal gland in one of the cases. The amebas in all four cases were
      identified as Balamuthia mandrillaris (Leptomyxiidae) based on their reactivity
      with the anti-Balamuthia (Leptomyxiidae) serum in an immunofluorescence test.

PMID- 9230788
TI  - Short report: one case of nasal human myiasis caused by third stage instar larvae
      of Oestrus ovis.
AB  - This is a report of a case of human nasal myiasis caused by third instar larvae
      of the sheep nasal bot fly, Oestrus ovis. Female flies rarely deposit first
      instar larvae in the eye, nostrils, and external auditory canal of humans, where
      they usually survive only a few days without further development. One human
      infestation by third instar larvae of O. ovis has been recorded in an patient
      infected with human immunodeficiency virus (HIV) in the United Kingdom. Our
      report describes a new case of nasal myiasis caused by the third instar larvae of
      the sheep bot fly in a patient without HIV or signs of any other disease.

PMID- 9230789
TI  - Human Bertiella studeri in Spain, probably of African origin.
AB  - A mature tapeworm and gravid proglottids of Bertiella studeri were reported from
      the stools of a 33-year-old pregnant Spanish woman. The patient had spent the six
      months preceding this discovery in Kenya. The evidence suggests a case of
      parasitism imported to Spain from the African continent. The patient presented no
      symptoms related to the parasite and the discovery in stools of a number of
      active, white structures led her to collect them. A morphologic and morphometric
      description of the material obtained is presented. Mebendazole failed to remove
      the parasite but niclosamide was effective.

PMID- 9230790
TI  - Open randomized trial of oral artemether alone and a sequential combination with
      mefloquine for acute uncomplicated falciparum malaria.
AB  - One hundred fifty-one patients with acute uncomplicated falciparum malaria were
      enrolled in a randomized, open-label study of oral artemether given alone for
      five or seven days or a sequential treatment of oral artemether followed by
      mefloquine. Forty patients received oral artemether, 100 mg initially, then 50 mg
      every 12 hr for a total dose of 500 mg over a five-day period: Group I. Fifty
      eight patients received oral artemether, 100 mg initially, then 50 mg every 12 hr
      for a total dose of 750 mg over a seven-day period: Group II. Fifty-three
      patients received oral artemether, 200 mg every 8 hr for a total dose of 600 mg,
      followed 8 hr later with mefloquine (1,250 mg divided into two doses given 6 hr
      apart: Group III. All patients were admitted to the hospital for 28 days to
      exclude reinfection and 131 patients remained through the 28-day follow-up. Only
      two, nine, and nine patients in Groups I, II, and III, respectively, left the
      hospital prior to study completion for reasons unrelated to their treatment. Cure
      rates for the three groups were 74% (28 of 38) for Group I, 98% (48 of 49) for
      Group II, and 98% (43 of 44) for Group III. Mean fever and parasite clearance
      times were not significantly different (32.8, 27.5, and 31.4 hr for fever
      clearance times and 40.2, 40.6, and 36.7 hr for parasite clearance times of
      Groups I, II, and III, respectively) nor were any adverse effects seen. In vitro
      drug susceptibility testing of admission and recrudescent parasite isolates was
      conducted for 10 patients. These data showed no decreased response to artemether
      or dihydroartemisinin in recrudescent isolates when compared with admission
      isolates. The results of this study suggest that sequential treatment for two
      days with oral artemether (600 mg) followed by mefloquine (1,250 mg) is effective
      and well-tolerated in patients with acute uncomplicated falciparum malaria and
      may be an alternative treatment for multidrug-resistant falciparum malaria,
      particularly useful for treating patients in rural areas where the period of
      admission to the hospital should be as short as possible. A seven-day regimen of
      artemether alone (750 mg) is also very effective, yet requires prolonged
      administration of drug after malaria symptoms disappear.

PMID- 9230791
TI  - Whole blood chloroquine concentrations with Plasmodium vivax infection in Irian
      Jaya, Indonesia.
AB  - Whole blood concentrations of self-administered chloroquine (CQ) and its
      metabolite desethylchloroquine (DCQ) were measured in 168 patients with
      microscopically confirmed infection by Plasmodium vivax in northeastern Irian
      Jaya, Indonesia. The study consisted of both survey and passive case detection in
      four separate villages between 1992 and 1994. The subjects were Javanese people 4
      51 years old who had lived in the Arso region for up to two years. The sum of CQ
      and DCQ ranged from 0 to 8,342 ng/ml of whole blood, and 122 subjects (73%) had >
      or = 100 ng/ml of CQ plus DCQ, the estimated minimally effective concentration
      (MEC) in whole blood against chloroquine-sensitive P. vivax. Among 56 subjects
      reporting to a clinic with symptoms of malaria, 53 (95%) had ordinarily effective
      levels of chloroquine in blood. Among 109 largely asymptomatic malaria patients
      found by survey case detection, 69 (63%) had chloroquine blood levels greater
      than the MEC. Virtually all clinical and most subclinical vivax malaria in this
      region occurs despite ordinarily effective levels of chloroquine in blood.

PMID- 9230792
TI  - Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence
      and whole blood chloroquine levels.
AB  - To develop criteria for the diagnosis of resistance to chloroquine using an in
      vivo test, we examined published records of early clinical trials of quinine and
      chloroquine against Plasmodium vivax. These data established the timing of
      relapse by tropical P. vivax relative to therapy by these drugs. The first
      relapse occurred 17 days after initiating and three days after terminating
      quinine therapy. The median day of relapse was day 23, and 59% of the patients
      had relapsed by day 30 (n = 333). In contrast, no relapse occurred until day 36
      following chloroquine treatment (n = 256). Data from our laboratory may help
      explain this difference; among 91 Indonesian patients with malaria, the mean
      whole blood levels of chloroquine (CQ) and desethylchloroquine (DCQ) were 141
      ng/ml (95% confidence interval = 115-167) on day 28 after initiating standard
      therapy (25 mg base/kg in three doses over a 48-hr period). This exceeds the
      estimated minimal effective concentration of chloroquine (100 ng/ml of whole
      blood). Thus, chloroquine lingering in the blood for at least 28 days after
      starting standard therapy was sufficient to eliminate or at least suppress
      chloroquine-sensitive tropical P. vivax. We conclude that a parasitemia by P.
      vivax recurring in the 28 days after full compliance to standard chloroquine
      therapy demonstrates resistance. If the recurrence appears before day 16, it is
      almost certainly a recrudescence and between days 17 and 28 it may be either a
      recrudescence or a relapse by chloroquine-resistant parasites. Recurrences beyond
      day 28 could be relapse by chloroquine-sensitive P. vivax.

PMID- 9230793
TI  - In vivo resistance to chloroquine by Plasmodium vivax and Plasmodium falciparum
      at Nabire, Irian Jaya, Indonesia.
AB  - A survey of resistance to chloroquine by Plasmodium vivax and P. falciparum was
      conducted during May 1995 at three mesoendemic villages 30 km southeast of
      Nabire, near the central northern coast of Irian Jaya, Indonesia. The prevalence
      of malaria at Urusumu (n = 157), Margajaya (n = 573), and Topo (n = 199) was 18%.
      9%, and 9%, respectively, with spleen rates among children of 79%, 10%, and 27%.
      Infected patients among those screened formed a study population of 64 subjects
      eligible for a 28-day in vivo test of resistance to chloroquine. Sixty-three
      patients successfully completed the test; 45 males and 18 females 1-60 years of
      age, of whom 29 were Javanese transmigrants of five years residence in Irian Jaya
      and 34 were native to Irian Jaya. The seven-day day cumulative incidence of
      therapeutic failure for P. vivax and P. falciparum was 15% (n = 34) and 30% (n =
      37). The 14- and 28-day estimates of cumulative incidence were 45% and 64% for P.
      vivax and 58% and 89% for P. falciparum. Almost all recurrences appeared in the
      face of ordinarily effective levels of chloroquine and its major metabolite,
      desethylchloroquine, in whole blood (> or = 100 ng/ml). Four infections by P.
      malariae in subjects enrolled in this study cleared by day 2 and none reappeared
      within 28 days. Chloroquine no longer provides effective therapy for falciparum
      or vivax malaria along the northern coast of Irian Jaya, Indonesia.

PMID- 9230794
TI  - Attempt to correlate urine arsenic excretion with clinical course during
      melarsoprol therapy of patients with Rhodesian trypanosomiasis.
AB  - This study enrolled 28 CNS-involved patients with Trypanosoma brucei rhodesiense
      at the Kenya Trypanosomiasis Research Institute (Alupe, Kenya) to examine
      treatment efficacy and toxicity of melarsoprol in relation to renal
      excretion/dose relationships. This study complied with World Health Organization
      treatment recommendations, initially treating with suramin followed by three
      courses of melarsoprol. Traced study patients had a relapse rate of 4.1%. The
      toxicity and crude death rate was 7.1%. Total urine arsenic output was measured
      between 24 and 48 hr after the last dose for each course. The range of means of
      total urine arsenic output between the three treatment courses was 356-511
      micrograms. There was no correlation comparing melarsoprol dose, estimated
      creatine clearance, or urine arsenic output. Urinary pharmacokinetic parameters
      are not predictive of toxicity or therapeutic efficacy.

PMID- 9230795
TI  - Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal
      parasitic infections associated with acquired immunodeficiency syndrome in
      tropical Africa.
AB  - Eighteen patients hospitalized with intestinal parasitic infections associated
      with diarrhea and dehydration completed a study of nitazoxanide in the treatment
      of Cryptosporidium parvum and other intestinal parasitic infections. Seventeen of
      the 18 patients were positive for human immunodeficiency virus. Twelve patients
      were diagnosed with clinical Stage 4 acquired immunodeficiency syndrome (AIDS)
      according to the 1990 World Health Organization proposed clinical classification
      system and cryptosporidiosis. Nitazoxanide (500 mg tablets) were administered
      orally, one tablet twice a day for seven consecutive days. Cryptosporidium parvum
      oocysts were eradicated or reduced by more than 95% in seven of the 12 Stage 4
      AIDS patients who completed the study based upon two post-treatment fecal
      examinations conducted on days 7 and 14 following the initiation of treatment.
      The elimination or reduction of C. parvum oocysts was associated with a complete
      resolution of diarrhea in four of the seven patients. The test drug was also
      effective against cases of Isospora belli, Entamoeba histolytica, Giardia
      lamblia, Ascaris lumbricoides, Enterobius vermicularis, Hymenolepis nana, and
      Dicrocoelium dentriticum. Treatment with nitazoxanide was well tolerated by the
      patients. There were no abnormalities in blood chemistry or hematology data that
      were considered to be attributable to nitazoxanide therapy. Transient episodes of
      vomiting were observed in four patients, all with Stage 4 AIDS and
      cryptosporidiosis, which resolved spontaneously without discontinuation of
      treatment and were not considered to be related to administration of
      nitazoxanide.

PMID- 9230796
TI  - Chronicity in Strongyloides stercoralis infections: dichotomy of the protective
      immune response to infective and autoinfective larvae in a mouse model.
AB  - Strongyloidiasis is an intestinal disease that can last for decades due to the
      occurrence of autoinfective larvae (L3a) in an infected person, which contribute
      to the maintenance of the population of adult worms in the intestine. The goal of
      the present study was to determine if L3a are susceptible to the protective
      immunity that targets the infective stage of the worm, the third-stage larvae
      (L3). Mice immunized and challenged with Strongyloides stercoralis L3 kill more
      than 90% of challenge larvae contained within diffusion chambers. The L3 do not
      remain antigenically static in mice, however, but undergo some degree of
      antigenic change before they are killed, becoming host-activated larvae (L3+).
      The L3/L3+ are killed in this model system by the combined effects of both
      parasite-specific IgM and eosinophils. Mice immunized with L3 were able to kill
      L3/L3+, but did not kill L3a, in challenge infections. Eosinophils were, however,
      present in diffusion chambers containing L3a, and IgM bound to the surface of
      L3a. We hypothesized that differential IgM recognition of soluble L3a, L3, and
      L3+ antigens is the reason why the immune response generated against L3 could not
      kill L3a. Many common antigens on L3, L3+, and L3a were recognized by serum from
      mice immunized with L3, as determined by immunoblotting. However, several unique
      L3, L3+, and L3a antigens were also recognized by immune serum, thus indicating
      that antigen recognition with IgM antibodies is different between the L3, L3+,
      and L3a stages. This difference in antigen recognition could explain why L3a are
      able to evade the immune response that targets L3/L3+ in chronically infected
      hosts.

PMID- 9230797
TI  - Assessment of age-dependent immunity to malaria in transmigrants.
AB  - Sixty-six Javanese transmigrants moving from Java, an area of very low malaria
      transmission, to Irian Jaya, an area of high malaria transmission, were monitored
      to evaluate the effects of exposure to malaria transmission and age on resistance
      to infection and the induction of humoral immunity. The risk of acquiring
      Plasmodium falciparum parasitemia was not statistically greater in children (5-15
      years of age) than in adults (> 15 years of age) during the first 14 months of
      exposure. However, during the cross-sectional survey at 14 months of exposure.
      children did have significantly higher P. falciparum asexual blood-stage parasite
      densities. Serum antibody titers to R32LR, a peptide containing sequences from
      the P. falciparum circumsporozoite repeat region, and MSP19, a proteolytic
      fragment of merozoite surface protein-1 (MSP-1) from P. falciparum, were measured
      by enzyme-linked immunosorbent assay. Exposure for both six and 14 months
      produced statistically significant increased antibody titers to both R32LR and
      MSP-1; no age-dependent difference in antibody titers was observed. In this
      population, exposure to malaria transmission induced antibodies to antigens
      associated with immunity to malaria. In addition, we noted an age-dependent
      difference in the parasitemia density of P. falciparum.

PMID- 9230799
TI  - Measuring the economic cost of malaria to households in Sri Lanka.
AB  - The economic cost at the household level of labor days lost due to malaria and
      other illnesses was estimated in a rural community in Sri Lanka. Over a one-year
      period, 223 episodes of malaria were recorded from the 298 inhabitants of the
      village. Based on daily activity records, the economically active age group was
      defined as 14-60 years. In this age group, 1.8% of working days were lost due to
      malaria and 5.2% due to all other illnesses. The value of a labor day lost was
      based on the actual rural wage rate for children, women, and men, with weeks
      during periods of high labor demand weighting more than weeks during lean
      agricultural periods. In this way the annual economic loss per household amounted
      to US $15.56 for malaria and US $47.46 for all other illnesses. This corresponded
      to a loss of 6% and 18% of annual household net income, respectively. Although
      the overall economic impact was limited, malaria cases were concentrated in an
      important agricultural season. During this season, 5.6% of working days were lost
      due to malaria. In addition, children, who were not part of the economically
      active population, lost 10% of school days due to malaria during the high
      transmission season. In estimating the socioeconomic impact of malaria and in
      measuring cost-benefits of malaria control interventions, these costs have to be
      considered together with direct expenditures incurred by households such as on
      treatment and travel and with costs for the service providers.

PMID- 9230798
TI  - Immunodiagnosis of human leptospirosis by dot-ELISA for the detection of IgM,
      IgG, and IgA antibodies.
AB  - A dot-ELISA was evaluated using antigen obtained from Leptospira interrogans
      cultures of the serovars brasiliensis, canicola, cynopteri, hebdomadis, and
      icterohaemorrhagiae for the detection of human IgM, IgG, and IgA. Single serum
      samples from 63 patients with the icterohemorrhagic form of leptospirosis in the
      acute phase, collected 3-14 days (mean = 7 days) after the onset of symptoms were
      tested. Ten patients were examined during convalescence and followed up for a
      period of 4-12 months. For a control group, serum samples from 10 apparently
      healthy individuals with no clinical or epidemiologic history of leptospirosis,
      and from 38 patients with nonleptospiral illnesses were used. In the acute phase,
      IgM antibodies were detected in 62 (98%) of 63 patients and IgG and IgA were
      observed in 70% and 76% of them, respectively. For the admission serum samples,
      the predictive value negative of the dot-ELISA was 98% for IgM, 72% for IgG, and
      76% for IgA detection. All 10 patients followed-up during convalescence showed
      IgM antibodies up to the sixth month, decreasing to 57% by the 10th month, and
      persisting in only one of six patients during the 11th and 12th months of follow
      up. Immunoglobulin G was detected in six patients up to the fourth month and in
      two of six individuals up to the end of follow-up. Immunoglobulin A was observed
      in all patients up to the end of the first month, decreasing progressively up to
      the sixth month, and was no longer detected in any patients from seventh to the
      12th months of follow-up. The dot-ELISA can be used as an important laboratory
      screening test, especially when detecting IgM antibodies. It proved to be
      effective in the diagnosis of human leptospirosis, and appears to have advantages
      in terms of yield, time, and case of execution and low cost.

PMID- 9230800
TI  - Venezuelan equine encephalitis and Oropouche virus infections among Peruvian army
      troops in the Amazon region of Peru.
AB  - An outbreak of a febrile illness characterized by headache, ocular pain, myalgia,
      and arthralgia occurred during June 1994 among Peruvian army troops in Northern
      Peru. On June 14-16, 1994, clinical data and blood samples were obtained from
      eight soldiers with a febrile illness, and from 26 others who had a history of
      febrile illness during the past three months. A follow-up blood sample was
      obtained 107 days later from four of the febrile and seven of the afebrile
      soldiers. Serum samples were tested for dengue (DEN), Oropouche (ORO), and
      Venezuelan equine encephalitis (VEE) IgM and IgG antibodies by an enzyme-linked
      immunosorbent assay (ELISA). Virus isolation was performed by inoculation of
      newborn mice and Vero cell cultures. Viral isolates were identified by
      immunofluorescence, ELISA, and nucleotide sequencing. A VEE virus infection was
      confirmed in three of the eight febrile soldiers, two by virus isolation, and one
      by serology. Antigenic analysis indicated that one of the virus isolates was
      similar to VEE subtype I, variety ID, viruses previously isolated in Colombia and
      Venezuela. Nucleotide sequence data showed that both viral isolates were
      identical to one another and closely related to VEE ID viruses previously
      isolated in Peru, Colombia, and Venezuela. Serologic results showed that two of
      26 afebrile soldiers had IgM antibody to VEE and four had IgG antibody to VEE;
      two febrile soldiers had IgG antibody in their first serum samples. Oropouche
      specific IgM antibody was detected in one of the eight febrile and five of the
      afebrile soldiers, and 18 of the 34 soldiers had low titers of ORO IgG antibody
      titers, which did not meet the diagnostic criteria for confirmed cases. All
      soldiers were negative for DEN IgM antibody, and 10 had flavivirus IgG antibody
      that reacted with DEN antigens. These data indicated that VEE ID virus was one of
      the causes of illness among Peruvians soldiers and that this was the first
      association of this VEE subtype with human disease in Peru.

PMID- 9230801
TI  - Evaluation of a stage-specific proteolytic enzyme of Schistosoma mansoni as a
      marker of exposure.
AB  - Cercarial elastase (CE) is one of the first proteins released in the host by
      invading schistosome cercariae. An enzyme-linked immunosorbent assay (ELISA)
      formatted immunoassay has been developed to detect antibodies to the stage
      specific CE antigen of Schistosoma mansoni as marker of exposure. We have
      evaluated this test system as an epidemiologic tool, using well-characterized
      sera collected from S. mansoni- and S. haematobium-infected subjects residing in
      endemic areas and from control subjects living in nonendemic areas in Egypt.
      Urine, stool specimens, and blood samples were collected from a sample of 272
      endemic subjects randomly selected to represent different age groups in the range
      of 2-20 years of age. Of 47 S. mansoni-infected subjects, 41 (87.2%) had anti-CE
      IgG antibodies. Of 52 S. haematobium-infected cases, 38 (73.0%) had IgM
      antibodies to CE and 43 (82.7%) had IgG antibodies to CE. Of 173 egg-negative
      people in the endemic area, 84 (48.6%) were IgM positive and 99 (57.2%) were IgG
      positive. The mean IgM and IgG antibody levels were similar in the infected
      groups but were significantly lower in the egg-negative group (P = 0.001). All
      sera from young children (2-3 years of age) were uniformly ELISA negative. The
      prevalence of IgM and IgG antibodies to CE in children less than six years of age
      were significantly lower than in other age groups. There was no significant
      difference in prevalence rates of IgM and IgG anti-CE antibodies between subjects
      having other parasites present in the endemic area (Ascaris lumbricoides,
      Entrobius vermicularis, Hymenolepis nana, H. diminuta, Trichostrongylus spp., and
      Entamoeba histolytica) and those without any parasitic infection. All nonendemic
      sera (58), including those with other helminth infections, were uniformly ELISA
      negative for antibodies to CE. These findings suggest that antibodies to elastase
      indicate exposure, but not necessarily active schistosome infection.

PMID- 9230802
TI  - High prevalence of hantavirus antibodies in bank voles (Clethrionomys glareolus)
      captured in the vicinity of households afflicted with nephropathia epidemica.
AB  - Puumala virus, the causative agent of nephropathia epidemica (NE), occurs
      endemically in Europe and is spread mainly by the bank vole (Clethrionomys
      glareolus). In the vicinity of each of four households afflicted with NE, we
      studied rodents with regard to population density and prevalence of Puumala virus
      specific antibodies. For each case area, a control area was randomly selected 10
      km away, without regard to the presence of human settlement. During 6,000 trap
      nights, 328 rodents were caught, of which 299 were C. glareolus. The mean rodent
      densities of case and control areas were 6.6 and 3.7 animals per 100 trap nights
      (P < 0.001). The prevalence of serum antibodies was 15.9% in case areas compared
      with 5.6% in control areas (P < 0.05). In three of the case areas, where NE had
      occurred 3-10 weeks before trapping, the rodent density and seroprevalence were
      much higher than in the fourth area, where NE occurred 38 weeks before trapping.
      In conclusion, C. glareolus seropositive for Puumala virus occurred more
      frequently near households afflicted with NE than in control areas 10 km away.

PMID- 9230803
TI  - Short report: geographic distribution of different genetic types of Ehrlichia
      chaffeensis.
AB  - The 120-kD protein gene of Ehrlichia chaffeensis was used to characterize
      ehrlichial DNA from seven pools of adult Amblyomma americanum ticks. Ticks from
      Missouri, Kentucky, and North Carolina contained E. chaffeensis DNA of the
      Arkansas strain genotype. Ticks from North Carolina also contained ehrlichiae of
      the Sapulpa strain genotype, originally identified in Oklahoma.

PMID- 9230804
TI  - Pancreatic mucinous ductal ectasia and intraductal papillary neoplasms. A single
      malignant clinicopathologic entity.
AB  - OBJECTIVE: The purpose of the study is to review a single institutional
      experience with mucinous ductal ectasia (MDE) and intraductal papillary neoplasms
      (IPNs) and to compare the clinicopathologic features of the two groups of tumors.
      SUMMARY BACKGROUND DATA: Mucinous ductal ectasia and IPNs represent newly
      recognized categories of pancreatic exocrine tumors, previously confused with
      pancreatic cystic neoplasms. The natural history of MDE and IPN is not well
      understood, and it is unclear whether MDE and IPN represent two distinct tumors
      or the same clinicopathologic entity. METHODS: The authors reviewed the clinical
      presentation, treatment, histopathology, and outcomes of 23 patients diagnosed
      with MDE or IPN at their institution over the past 6 years. RESULTS: The mean age
      at presentation for the cohort of patients with MDE and IPN was 62.5 years. The
      prevalence of abdominal pain was 75%, jaundice 25%, weight loss 42%, steatorrhea
      37.5%, diabetes 37.5%, and history of pencreatitis 29%. Serum CA 19-9 levels
      ranged from 0 to 5350 units/mL with high levels reflecting advanced disease.
      There were no significant differences between MDE and IPN with respect to these
      parameters. Both MDE and IPN comprised papillary villous epithelial neoplasms
      involving the main and large pancreatic ducts. The tumors ranged from a few
      millimeters in size to panductal and were distinguished easily from cystic
      neoplasms in all cases. Invasive carcinoma was present in 11 (46%) of 24
      patients, carcinoma in situ in an additional 10 (42%) of 24 patients, and low
      grade dysplasia in the remaining 3 (12%) of 24 patients. Mucinous ductal ectasia
      and IPN differed histopathologically only in degree of mucin secretion and tumor
      location. Mucinous ductal ectasia, but not IPN, was characteristically mucin
      hypersecreting and more frequently involved the head of the gland than did IPN
      (11/16 vs. 1/8 p < 0.04). All patients were explored surgically and 20 (83%) of
      24 of the tumors were resectable with frozen section control of the duct margins
      (9 pancreatoduodenectomies, 4 distal pencreatectomies, 7 total pancreatectomies).
      Despite the 88% prevalence of cancer, the overall survival at a mean follow-up of
      21 months was 13 (87%) of 15 for MDE and 5 (71%) of 7 for IPN. CONCLUSIONS:
      Intraductal papillary neoplasms with or without MDE represent a spectrum of main
      duct papillary tumors ranging from adenoma to carcinoma with differing amounts of
      extracellular mucin production. Malignant IPNs with or without MDE typically
      exhibit extensive intraductal growth but are slow to invade the periductal
      tissues and slow to metastasize. The majority of patients with these tumors have
      resectable disease and a favorable prognosis; endoscopic therapy is
      inappropriate. The encompessing term intraductal papillary-mucinous tumors is
      appropriate.

PMID- 9230805
TI  - A randomized, prospective comparison of the Nissen fundoplication versus the
      Toupet fundoplication for gastroesophageal reflux disease.
AB  - OBJECTIVE: A prospective, randomized trial was performed to determine which of
      two antireflux procedures, a complete wrap (Nissen) or a 200N wrap (Toupet), was
      more effective with fewer sequelae. SUMMARY BACKGROUND DATA: Laparoscopic
      procedures for gastroesophageal reflux disease appear to be as effective as those
      done by open laparotomy. The Nissen fundoplication is used most frequently, but
      postoperative bloating, inability to belch, and dysphagia occur. The partial wrap
      has been said to be as effective with less unfavorable postoperative symptoms.
      METHODS: Patients with reflux esophagitis were approached laparoscopically using
      a six-port technique. After division of the short gastric vessels and dissection
      of the terminal esophagus and fundus of the stomach to allow performance of
      either procedure, patients randomly were assigned one of the procedures by a card
      drawn in the operating room. RESULTS: Forty patients underwent operation, but 1
      was excluded when an open procedure became necessary. Twenty-three patients
      received a complete wrap and 16 received a partial wrap. The average operating
      time was 155 minutes for the Nissen procedures and 162 minutes for the Toupet
      procedures. The postoperative stay averaged 2.7 days for the Nissen procedures
      and 2.5 days for the Toupet procedures. There were no deaths. Including the
      patient converted to an open procedure, three patients had operative
      complications. At follow-up, Visick scores after the complete wraps were I-13, II
      8, III-2 and after the partial wrap were I-12 and II-3. Two patients indicated
      they would not have the operation again. CONCLUSIONS: A partial or a complete
      wrap after division of the short gastric vessel offers effective therapy for
      reflux esophagitis with > 90% patient satisfaction. The authors' study shows no
      clear advantage of one wrap (partial or complete) over the other.

PMID- 9230806
TI  - Laparoscopic Heller myotomy and fundoplication for achalasia.
AB  - OBJECTIVE: The goal of this study was to review the authors' results with
      laparoscopic cardiomyotomy and partial fundoplication for achalasia. SUMMARY
      BACKGROUND DATA: Pneumatic dilatation and botulinum toxin (BOTOX) injection of
      the lower esophageal sphincter largely have replaced cardiomyotomy for treatment
      of achalasia. After a brief experience with a thoracoscopic approach, the authors
      elected to perform cardiomyotomy laparoscopically, in combination with a partial
      fundoplication (anterior or posterior). PATIENTS AND METHODS: Forty patients were
      treated between July 1992 and November 1996. Thirty patients had previous therapy
      of achalasia, 21 with pneumatic dilation, 1 with BOTOX, 6 with balloon and BOTOX,
      and 2 with transthoracic cardiomyotomy. Three patients had previous laparoscopic
      fundoplication for gastroesophageal reflux. Symptom scores (0 = none to 4 =
      disabling) were obtained before surgery and after surgery. Barium swallows and
      esophagogastroduodenoscopy were performed in all patients. Esophageal motility
      study was performed in 36 patients. Laparoscopic Heller myotomy and
      fundoplication was performed through five upper abdominal trocars. A 7-cm myotomy
      extended 6 cm above the GE junction and 1 cm below the GE junction. A posterior
      fundoplication was performed in 32 patients, anterior fundoplication in 7
      patients, and no fundoplication in 1 patient. Statistical inference was performed
      with a Wilcoxon signed rank test. RESULTS: Mean operative duration was 199 +/-
      36.2 minutes. Mean hospital stay was 2.75 days (range, 1-13 days). Dysphagia was
      alleviated in all but four patients (90%), and regurgitation in all but two
      patients (95%) (p < 0.001). Chest pain and heartburn improved significantly (p <
      0.01) as well. Intraoperative complications included mucosal laceration in six
      patients and hypercarbia in one. Postoperative pneumonia developed in two
      patients, and one patient had moderate hemorrhage from an esophageal ulcer 2
      weeks after surgery. CONCLUSIONS: Laparoscopic cardiomyotomy and fundoplication
      appears to provide definitive treatment of achalasia with rapid rehabilitation
      and few complications.

PMID- 9230808
TI  - Proximal gastric cancers resected via a transabdominal-only approach. Results and
      comparisons to distal adenocarcinoma of the stomach.
AB  - OBJECTIVE: The purpose of this study is to compare the outcome of patients with
      proximal gastric cancer (PGC) treated by a transabdominal-only resection to that
      of patients with distal gastric cancer (DGC). SUMMARY BACKGROUND DATA: It has
      been suggested that PGC is inherently more aggressive than DGC. The worse
      survival of PGC compared with that of DGC may be in part, because of the
      difficulty distinguishing PGC from distal esophageal adenocarcinoma. By defining
      a subset of PGC resected using an transabdominal-only approach, one may
      discriminate true PGC from distal esophageal adenocarcinoma. This subset of
      patients is a more appropriate comparison group when analyzing outcome relative
      to patients with DGC. METHODS: A review of the prospective database for gastric
      adenocarcinoma at Memorial Sloan-Kettering Cancer Center between July 1985 and
      August 1995 identified 98 patients with PGC resection via a transabdominal-only
      approach. Of these, 65 underwent proximal gastrectomy and 33 underwent total
      gastrectomy. For DGC, 258 required a distal gastrectomy and 71 required total
      gastrectomy. RESULTS: The overall 5-year survival of patients with PGC was 42%
      (median survival, 47 months), whereas the 5-year survival for patients with DGC
      was 61% (median survival, 106 months, p = 0.03). Within each stage, there were no
      significant survival differences, but in all stages, survival was better for
      patients with DGC. More important, the site of the primary tumor appears to
      affect survival, with a worse outcome as the tumor moves proximally. CONCLUSIONS:
      Despite excluding distal esophageal cancers, survival for patients with PGC
      remains worse than for those with DGC. Late stage of presentation could not
      explain this difference. It appears that PGCs are inherently more aggressive than
      are DGCs. In addition, site of the primary tumor appears to affect outcome, with
      a trend toward a worse outcome as the tumor moves proximally.

PMID- 9230807
TI  - Randomized prospective trial comparing ileal pouch-anal anastomosis performed by
      excising the anal mucosa to ileal pouch-anal anastomosis performed by preserving
      the anal mucosa.
AB  - OBJECTIVE: The purpose of the study is to compare the results of ileal pouch-anal
      anastomosis (IPAA) in patients in whom the anal mucosa is excised by handsewn
      techniques to those in whom the mucosa is preserved using stapling techniques.
      SUMMARY BACKGROUND DATA: Ileal pouch-anal anastomosis is the operation of choice
      for patients with chronic ulcerative colitis requiring proctocolectomy.
      Controversy exists over whether preserving the transitional mucosa of the anal
      canal improves outcomes. METHODS: Forty-one patients (23 men, 18 women) were
      randomized to either endorectal mucosectomy and handsewn IPAA or to double
      stapled IPAA, which spared the anal transition zone. All patients were diverted
      for 2 to 3 months. Nine patients were excluded. Preoperative functional status
      was assessed by questionnaire and anal manometry. Twenty-four patients underwent
      more extensive physiologic evaluation, including scintigraphic anopouch angle
      studies and pudendel never terminal motor latency a mean of 6 months after
      surgery. Quality of life similarly was estimated before surgery and after
      surgery. Univariate analysis using Wilcoxon test was used to assess differences
      between groups. RESULTS: The two groups were identical demographically. Overall
      outcomes in both groups were good. Thirty-three percent of patients who underwent
      the handsewn technique and 35% of patients who underwent the double-stapled
      technique experienced a postoperative complication. Resting anal canal pressures
      were higher in the patients who underwent the stapled technique, but other
      physiologic parameters were similar between groups. Night-time fecal incontinence
      occurred less frequently in the stapled group but not significantly. The number
      of stools per 24 hours decreased from preoperative values in both groups. After
      IPAA, quality of life improved promptly in both groups. CONCLUSIONS: Stapled
      IPAA, which preserves the mucosa of the anal transition zone, confers no apparent
      early advantage in terms of decreased stool frequency or fewer episodes of fecal
      incontinence compared to handsewn IPAA, which excises the mucosa. Higher resting
      pressures in the stapled group coupled with a trend toward less night-time
      incontinence, however, may portend better function in the stapled group over
      time. Both operations are safe and result in rapid and profound improvement in
      quality of life.

PMID- 9230809
TI  - The incidence, morbidity, and mortality of surgical procedures after orthotopic
      heart transplantation.
AB  - OBJECTIVE: The authors present their experience with patients having undergone
      orthotopic heart transplantation (OHT) in whom surgical conditions subsequently
      developed that required operative intervention. The incidence, morbidity, and
      mortality of these procedures are reported. SUMMARY BACKGROUND DATA: Several
      studies have evaluated the management options of biliary tract disease after OHT.
      Multiple reports of patients having undergone OHT who subsequently underwent
      peripheral vascular reconstructions, plastic reconstructive, and thoracic
      procedures also have been published. METHODS: A chart review of 349 patients who
      underwent OHT between 1985 and 1996 was conducted to identify surgical procedures
      that were required in the post-transplant period. Their outcomes are reported.
      RESULTS: Of 349 patients who underwent OHT, conditions requiring 94 surgical
      procedures developed in 54 patients (15%). Biliary tract disease developed in 17
      patients (5%) who required cholecystectomy, 2 of the 5 patients with acute
      cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no
      operative mortality. Flap advancements for sternal wound infections were
      performed in five patients and four deaths occurred. Seventeen thoracic
      procedures were performed in 11 patients with an overall mortality of 45%. Twenty
      one vascular procedures were performed on 17 patients with 1 delayed death due to
      a malignancy. Seven patients underwent procedures of the colon and rectum with no
      mortality. Seven patients underwent repair of inguinal or incisional hernias with
      no mortality. Various infections occurred with one resultant death after
      operative intervention. Six procedures were performed for diseases of the small
      intestine with no resultant mortalities. CONCLUSIONS: Patients having undergone
      OHT and chronic immunosuppression are at increased risk of having complications
      develop from infection. Acute cholecystitis and sternal wound infection caused an
      inordinate risk of complications and death. Malignancies developed in four
      patients who required surgical intervention. A heightened awareness of coexisting
      peripheral vascular disease in patients transplanted for ischemic cardiomyopathy
      should exist. Close screening before surgery and surveillance after surgery to
      identify risk factors for infection and vascular disease and to screen for
      malignancies are essential.

PMID- 9230810
TI  - Ventricular assist devices as a bridge to cardiac transplantation. A prelude to
      destination therapy.
AB  - OBJECTIVE AND BACKGROUND: Ventricular assist devices (VADs) have been used for
      temporary circulatory support pending transplantation or recovery of the native
      heart. Outcome in 38 patients treated at the authors' institution with VADs
      pending transplantation was analyzed to provide information relevant to the
      future use of VADs as permanent implants. METHODS: Thoratec (Thoratec
      Laboratories, Pleasanton, CA) or HeartMate (Thermo Cardiosystems, Woburn, MA)
      VADs were used in all cases. Patients were considered for VAD placement if they
      were candidates for cardiac transplantation and fulfilled the criteria for the
      Food and Drug Administration investigational Device Exemption trials. The
      following adverse events were included in the analysis; death during VAD support,
      device malfunction, bleeding, neurologic events, support-related events that
      preclude transplantation, and device-related infections. Patient survival and
      complication rates were quantified using the Kaplan-Meier method, competing risk
      analysis, and hazard functions. RESULTS: Nineteen patients had transplantation.
      Three patients had VAD removal after cardiac recovery and 16 died without
      transplantation. The duration of VAD support ranged from 0 to 279 days. The
      hazard function for death during VAD support had an early phase that lasted for 2
      weeks after VAD placement, and early death was related to the preimplant
      condition of the patient. Device-related infections were noted in 11 patients.
      Seven of these patients had transplantation after clearing the infection, whereas
      four died without transplantation. Neurologic events occurred in seven patients.
      There were no device malfunctions that led to patient death. CONCLUSIONS: The
      absence of fatal device malfunctions suggests that longer term support with
      current VAD designs is feasible. Appropriate patient selection, infection
      control, and avoidance of thromboembolic neurologic complications will be crucial
      to the success of permanent VAD use.

PMID- 9230812
TI  - Crohn's disease and ulcerative colitis are associated with the DNA repair gene
      MLH1.
AB  - OBJECTIVE: The purpose of this study was to determine whether there is an
      association between Crohn's disease and ulcerative colitis with MLH1. SUMMARY
      BACKGROUND DATA: Identification of genes involved in the etiology of inflammatory
      bowel disease may lead to the development of markers that objectively can define
      disease and permit therapy. The treatment of Crohn's disease of the colon and
      ulcerative colitis also is complicated by difficulties in differentiating the two
      conditions. METHODS: The DNA and clinical data were obtained on 126 unrelated
      individuals (45 Crohn's disease, 36 ulcerative colitis, and 45 control subjects
      without intestinal disease). Polymerase chain reaction products were analyzed by
      single-strand conformation polymorphisms (MLH1 exons 9, 11, 14, 15, and 16) and
      polyacrylamide gel electrophoresis (markers D3S1611 and D3S1768). All comparisons
      were analyzed by chi square test. The association between single haplotypes and
      disease was expressed as relative odds. RESULTS: MLH1 exons 9, 11, 14, and 16
      were monomorphic. Two, four, and six alleles were detected in MLH1 exon 15,
      D3S1611, and D3S1768, respectively. Significant associations were observed for
      MLH1 exon 15/D3S1611 haplotypes AB (OR = 5.5; p = 0.007) and BA (p = 0.002) with
      Crohn's disease and for haplotypes AB (OR = 4.0; p = 0.042), BA (p = 0.035), and
      BC (OR = 6.1; p = 0.016) with ulcerative colitis. Family history of inflammatory
      bowel disease was associated with D3S1768/D3S1611 (p = 0.05) and MLH1 exon
      15/D3S1611 haplotypes (p = 0.03). D3S1611/D3S1768 haplotype CD (OR = 11.3; p =
      0.03) was associated with disease, whereas MLH1 exon 15/D3S1611 haplotype AA (OR
      = 0.25; p = 0.02) was protective. Comparisons of MLH1 exon 15/D3S1611 haplotypes
      of Crohn's colitis and patients with ulcerative colitis were significant (p =
      0.037). CONCLUSIONS: This study identifies a novel genetic and clinical
      association between MLH1 and inflammatory bowel disease.

PMID- 9230811
TI  - Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity
      after parenteral nutrition.
AB  - OBJECTIVE: The authors characterize the recovery of parenteral nutrition-induced
      changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract
      immunity with enteral nutrition and provide further information defining the
      effects of enteral feeding on mucosal immunity. SUMMARY BACKGROUND DATA: The
      small intestine plays a prominent role in development and maintenance of mucosal
      immunity, both intestinal and extraintestinal, primarily through immunoglobulin A
      (IgA)-mediated mechanisms. Prior research has shown that mice fed total
      parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible
      for IgA production, as well as impaired upper respiratory tract immunity to viral
      challenge of previously immunized animals. The recovery of TPN-induced changes in
      GALT and upper respiratory tract immunity after enteral refeeding is studied.
      METHODS: Male institute of Cancer Research mice received 5 days of TPN followed
      by 0 to 4 days of chow. Small intestinal GALT was characterized by flow
      cytometry. In a second experiment, animals were immunized intranasally with
      moused-adapted influenza virus. Three weeks later, one group received a 5-day
      course of TPN followed by enteral refeeding for 5 days. A second group received
      TPN alone. Both groups were challenged with intranasal virus and killed 40 hours
      postchallenge to determine viral shedding from the upper respiratory tract.
      RESULTS: Animals fed TPN only had significantly fewer GALT lymphocytes compared
      with those chow-fed control subjects. Peyer's patch counts increased after a
      single day of refeeding, returning to normal levels by 48 hours. Lamina propria
      counts remained significantly depressed after 24 hours of refeeding, but also
      returned to normal after 48 hours of refeeding. The T-cell and B-cell populations
      mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal
      only after 72 hours of refeeding. None of the 9 animals refed enterally for 5
      days were positive for viral shedding, compared with 8 of 12 matched TPN-fed
      animals. CONCLUSIONS: Enteral refeeding after TPN is associated with rapid
      repletion of GALT cellularity, initially within Peyer's patches and subsequently
      within the lamina propria. Refeeding corrects the impairment of IgA-mediated
      upper respiratory tract antiviral immunity occurring with TPN administration.
      This work further enhances the authors' knowledge of the underlying immunologic
      differences influenced by routes of nutrition.

PMID- 9230813
TI  - Association of breast cancer with the finding of atypical ductal hyperplasia at
      core breast biopsy.
AB  - OBJECTIVE: The purpose of the study is to evaluate the prevalence of occult
      breast carcinoma in surgical breast biopsies performed on nonpalpable breast
      lesions diagnosed initially as atypical ductal hyperplasia (ADH) by core needle
      biopsy. BACKGROUND: Atypical ductal hyperplasia is a lesion with significant
      malignant potential. Some authors note that ADH and ductal carcinoma in situ
      (DCIS) frequently coexist in the same lesion. The criterion for the diagnosis of
      DCIS requires involvement of at least two ducts; otherwise, a lesion that is
      qualitatively consistent with DCIS but quantitatively insufficient is described
      as atypical ductal hyperplasia. Thus, the finding of ADH in a core needle breast
      biopsy specimen actually may represent a sample of a true in situ carcinoma.
      METHODS: Between May 3, 1994, and June 12, 1996, image-guided core biopsies of
      510 mammographically identified lesions were performed using a 14-gauge automated
      device with an average of 7.5 cores obtained per lesion. Atypical ductal
      hyperplasia was found in 23 (4.5%) of 510 lesions, and surgical excision
      subsequently was performed in 21 of these cases. In these 21 cases,
      histopathologic results from core needle and surgical biopsies were reviewed and
      correlated. RESULTS: Histopathologic study of the 21 surgically excised lesions
      having ADH in their core needle specimens showed seven (33.3%) with DCIS.
      CONCLUSIONS: In the authors' patient population, one third of patients with ADH
      at core biopsy have an occult carcinoma. A core needle breast biopsy finding of
      ADH for nonpalpable lesions therefore warrants a recommendation for excisional
      biopsy.

PMID- 9230814
TI  - Improved results of cervical reoperation for medullary thyroid carcinoma.
AB  - OBJECTIVE: The purpose of the study is to determine whether reoperation for
      medullary thyroid carcinoma (MTC), performed with low morbidity in carefully
      selected patients, consistently results in improvement as determined by lowering
      of stimulated calcitonin levels. BACKGROUND: Persistent or recurrent elevation of
      stimulated plasma calcitonin levels occurs in > 50% of patients after primary
      operation for MTC. Success of reoperation with clearance of metastatic cervical
      nodal disease has been hampered by failure to identify patients with distant
      metastases and by inadequate removal of involved nodal groups. METHODS: Since
      1992, the authors have evaluated 115 patients with recurrent or residual MTC.
      Fifty-three patients have not undergone operation because of extent of disease,
      previous extensive treatment, medical condition, or patient choice. Sixty-two
      patients underwent surgery. Ten patients had laparoscopic or open examination of
      the liver, the results of which showed liver metastases. Seven patients had
      palliative debulking of cervical tumor. In 45 patients without evidence of
      distant metastases, cervical operation was carried out with curative intent.
      Removal of central, upper mediastinal, and lateral nodes (levels II, III, IV, VI,
      and VII) was done. RESULTS: Seven of eight patients who had palliative resections
      are alive without symptoms. In patients who underwent curative resections,
      postoperative stimulated calcitonin levels were in the normal range in 17
      patients (38%) and were not significantly lowered in 6 patients (13%). There were
      no deaths, and no transfusions were used. CONCLUSIONS: These results are a
      significant improvement over the authors' previous series and reflect better
      preoperative identification of patients with disease confined to the neck and
      improved operative strategy based on knowledge of the pattern of nodal spread of
      MTC.

PMID- 9230815
TI  - Poor outcome from peritonitis is caused by disease acuity and organ failure, not
      recurrent peritoneal infection.
AB  - OBJECTIVE: The purpose of the study is to determine whether organ failure
      develops in patients despite control of peritoneal infection and whether the
      process is, in part, neutrophil (polymorphonuclear leukocyte [PMN]) mediated.
      SUMMARY BACKGROUND DATA: Peritonitis generally responds to prompt surgical
      intervention and systemic antibiotics; however, some patients continue a septic
      course and progress to organ failure and death. METHODS: One hundred five
      consecutive patients with peritonitis between 1988 and 1996 who required
      operation and a postoperative hospital stay greater than 10 days were studied.
      Mice were injected with a monoclonal anti-PMN antibody 24 hours before cecal
      ligation and puncture (CLP) to deplete PMNs. RESULTS: Thirty-eight patients died,
      and all but 1 had identified organ failure. Seventy-seven patients had either
      pulmonary failure alone (25 patients) or as a component of multisystem organ
      failure (52 patients). All but one of these patients showed resolution of their
      intraperitoneal infection as evident by clinical course, abdominal computed
      tomographic scan, second-look laparotomy, or autopsy. Recurrent intra-abdominal
      infection developed in 15 patients, but only 1 had organ failure, and 2 died. At
      18 hours after CLP, lung injury, PMN content, interleukin-1 mRNA expression, and
      liver injury were significantly reduced by anti-PMN treatment, whereas serum
      endotoxin levels actually increased. CONCLUSIONS: Disease acuity and organ
      failure, and not recurrent peritoneal infection, are the major causes of adverse
      outcome in patients with peritonitis. The authors' experimental data indicate
      that such organ injury is, in part, PMN mediated but not endotoxin mediated.
      Attraction of PMNs toward the site of primary infection, and thereby away from
      remote organs, is a logical future therapeutic approach in such patients who are
      critically ill with peritonitis.

PMID- 9230816
TI  - Integrin stimulation regulates polymorphonuclear leukocytes inflammatory cytokine
      expression.
AB  - OBJECTIVE: The purpose of these studies is to investigate the role of integrin
      binding on the regulation of polymorphonuclear leukocyte (PMN) cytokine receptor
      expression. SUMMARY BACKGROUND DATA: Current knowledge in this area revolves
      around the ability of beta 2 integrins to mediate PMN adherence and chemotaxis.
      The role of alpha 1-6/beta 1 integrins in regulating cytokine receptor expression
      has not been probed. METHODS: Purified human PMN were adhered on plastic,
      fibronectin, or laminin-coated surfaces followed by the addition of iodine 125
      (125I) monoclonal antibodies (mAbs) directed against tumor necrosis factor-alpha
      R (TNF-alpha R) p60, p80, or interleukin-1 beta R (IL-1 beta R) types I, II.
      Receptor expression was calculated based on the counts per minute (cpm) bound.
      The role of individual beta 1 integrins was assessed using mAbs directed against
      the alpha 1-6 subunit of the beta 1 complex, and integrin cross-linkage was
      achieved using secondary goat antimouse F(ab')2 antibodies. Polymorphonuclear
      leukocytes were pretreated with herbimycin A to determine the role of protein
      tyrosine kinase in mediating the effect of the beta 1 integrins. RESULTS:
      Adherence of PMN to Ln decreased IL-1 beta types I, II receptor expression,
      whereas adherence to Fn increased TNF-alpha R p60 and p80 expression. Anti-VLA-5
      (CD49e) but not anti-VLA-1 through VLA-4 and VLA-6, blocked the effect of Fn on
      TNF-alpha receptors, whereas anti-VLA-6 but not anti-VLA-1 through VLA-5 blocked
      the effect of Ln on IL-1 beta receptors. Modulation of IL-1 beta and TNF-alpha
      receptors by VLA-5 and VLA-6 required protein tyrosine kinase activation as
      herbimycin A (10 micrograms/mL) blocked the affect of Fn and Ln. Changes in PMN
      cytokine receptor expression led to parallel changes in functional activity as
      assessed by the binding of 125I IL-1 beta and TNF-alpha. CONCLUSIONS: Integrin
      stimulation regulates the cell surface expression of PMN cytokine receptors.
      Ligation of CD49e upregulates TNF-alpha receptor expression, whereas binding of
      CD49f downregulates IL-1 beta receptor expression. Both processes are protein
      tyrosine kinase dependent. Changes in PMN cytokine receptor expression led to
      corresponding changes in functional activity. These results provide the first
      demonstration that chemotaxis of PMN into the interstitium provides a mechanism
      for ongoing participation in the local inflammatory response and is regulated by
      matrix protein integrin receptors.

PMID- 9230817
TI  - Management of the infected median sternotomy wound with muscle flaps. The Emory
      20-year experience.
AB  - OBJECTIVE: The purpose of the study is to define those patient variables that
      contribute to morbidity and mortality of median sternotomy wound infection and
      the results of treatment by debridement and closure by muscle flaps. BACKGROUND:
      Infection of the median sternotomy wound after open heart surgery is a
      devastating complication associated with significant mortality. Twenty years ago,
      these wounds were treated with either open packing or antibiotic irrigation, with
      a mortality approaching 50% in some series. In 1975, the authors began treating
      these wounds with radical sternal debridement followed by closure using muscle or
      omental flaps. The mortality of sternal wound infection has dropped to < 10%.
      METHODS: The authors' total experience with 409 patients treated over 20 years is
      described in relation to flap choices, hospital days after sternal wound closure,
      and incidence rates of morbidity and mortality. One hundred eighty-six patients
      treated since January 1988 were studied to determine which patient variables had
      impact on rates of flap closure complications, recurrent sternal wound infection,
      or death. Variables included obesity, history of smoking, hypertension, diabetes,
      poststernotomy septicemia, internal mammary artery harvest, use of intra-aortic
      balloon pump, and perioperative myocardial infarction and were analyzed using chi
      square tests. Fisher's exact tests, and multivariable logistic regression
      analysis. RESULTS: The mortality rate over 20 years was 8.1% (33/49). Additional
      procedures for recurrent sternal wound infection were necessary in 5.1% of
      patients. Thirty-one patients (7.6%) required treatment for hematoma, and 11
      patients (2.7%) required hernia repair. Among patients treated since 1988,
      variables strongly associated with mortality were septicemia (p < 0.00001),
      perioperative myocardial infarction (p = 0.006), and intra-aortic balloon pump (p
      = 0.0168). Factors associated with wound closure complications were intra-aortic
      balloon pump (p = 0.0287), hypertension (p = 0.0335), and history of smoking (p =
      0.0741). Factors associated with recurrent infection were history of sternotomy
      (p = 0.008) and patients treated for sternal wound infection from 1988 to 1992 (p
      = 0.024). Mean hospital stay after sternal wound reconstruction declined from
      18.6 days (1988-1992) to 12.4 days (1993-1996) (p = 0.005). To clarify management
      decisions of these difficult cases, a classification of sternal wound infection
      is presented. CONCLUSIONS: Using the principles of sternal wound debridement and
      early flap coverage, the authors have achieved a significant reduction in
      mortality after sternal wound infection and have reduced the mean hospital stay
      after sternal wound closure of these critically ill patients. Further reductions
      in mortality will depend on earlier detection of mediastinitis, before onset of
      septicemia, and ongoing improvements in the critical care of patients with
      multisystem organ failure.

PMID- 9230819
TI  - Suitability and durability of multiple internal thoracic artery coronary artery
      bypasses.
AB  - OBJECTIVE: The authors evaluate operative and extended outcomes of coronary
      artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as
      bypass grafts. The authors conclude that the procedure is viable and of long-term
      benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met
      with early enthusiasm by the surgical profession, but skepticism and controversy
      arose with reports of increased operative morbidity, insufficient graft blood
      flow, a high incidence of failure of the right ITA, and uncertainty about
      durability and long-term benefits. METHODS: To assess the actual incidence and
      impact of these complications and long-term results, the authors prospectively
      studied 500 consecutive patients with multiple ITA bypasses, constituting the
      closely observed and carefully documented experience of one surgeon over an 11
      year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%,
      perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal
      wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine
      patients (1.8%) were returned to the operating room to control bleeding. One
      hundred ninety-eight patients who had abnormal stress test results before surgery
      were retested within 3 months of surgery. Ninety-four percent of these were
      normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of
      7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and
      93.2% of this group have experienced continuing good clinical results (New York
      Heart Association class I or II). Eighty-nine patients who underwent an angiogram
      had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only
      two patients required repeat operations. CONCLUSIONS: The operative results did
      not support the contention that the coronary artery bypass using ITA procedure
      produces higher than acceptable mortality and morbidity rates. Multiple ITA
      bypasses can be performed without excessive morbidity, with low reoperation rates
      and long-term outcomes that should encourage skeptics to reconsider the
      procedure's clinical value.

PMID- 9230818
TI  - Effect of repair strategy on hospital cost for infants with tetralogy of Fallot.
AB  - OBJECTIVE: This study compares the total hospital cost (HC) for one-stage versus
      "two-stage" repair of tetralogy of Fallot (TOF) in infants younger than 1 year of
      age. SUMMARY BACKGROUND DATA: Total (one-stage) correction of TOF is now being
      performed with excellent results in infancy. Alternatively, a two-stage approach,
      with palliation of infants in the first year of life, followed by complete repair
      at a later time can be used. In some institutions, the two-stage approach is
      standard practice for infants younger than 1 year of age or is used selectively
      in patients with an anomalous coronary artery across the right ventricular
      outflow tract (RVOT), "small pulmonary arteries," multiple congenital anomalies,
      critical illnesses (CI), which increase the risk of bypass (e.g., sepsis or DIC),
      or severe hypercyanotic spells (HS) at the time of presentation. The cost
      implications of these two approaches are unknown. METHODS: The authors reviewed
      22 patients younger than 1 year of age who underwent repair of TOF at their
      institution between 1993 and 1995. Eighteen patients had one-stage (1 degree)
      repair (mean age, 3.4 +/- 3.1 months; range, 3 days-9 months) and 4 patients were
      treated by a staged approach with initial palliation (1.6 +/- 0.4 month; range,
      1.5-2 months) followed by later repair (14.75 +/- 1.5 months; range, 13-16
      months). The reasons for palliation were severe HS at time of presentation (two
      patients), anomalous coronary artery (one patient) and CI (one patient). In the
      18 patients undergoing 1 degree repair, 3 (16.6%) presented with HS, 6 (33.3%)
      had a transanular repair, and 6 (33.3%) were able to be repaired through an
      entirely transatrial approach (youngest patient, 1.5 months). The HC (1996
      dollars) and hospital length of stay (LOS; days) were evaluated for all patients.
      The HCs were calculated using transition I, which is a cost accounting system
      used by our medical center since July 1992. Transition I provides complete data
      on all direct and indirect hospital-based, nonprofessional costs. RESULTS: There
      was no mortality in either group. The group undergoing 1 degree repair had an
      average LOS of 14.5 +/- 11.2 days compared to an average LOS for palliation of 14
      +/- 6.4 days. When the palliated group returned for complete repair, the average
      LOS was 28.8 +/- 25 days, yielding a total LOS for the two-stage strategy of 43
      +/- 30.8 days (p = 0.003 compared to 1 degree repair). The HC for 1 degree repair
      was $32,541 +/- $15,968 compared to $25,737 +/- $1900 for palliation (p = not
      significant compared to 1 degree repair) and $54,058 +/- $39,395 for subsequent
      complete repair (p = not significant compared to 1 degree repair) (total two
      stage repair HC = $79,795 +/- $40,625; p = 0.001 compared to 1 degree repair).
      The LOS and HC for the two-stage group combine a total of palliation plus later
      repair and, as such, reflect two separate hospitalizations and convalescent
      periods. To eliminate cost outliers, a best-case analysis was performed by
      eliminating 50% of patients from each group. Using this analysis, the two-stage
      approach resulted in an average (total) LOS of 16.5 +/- 2.1 days compared to 8.5
      +/- 1.4 days for the 1 degree group. Total cost for the two-stage strategy in
      this best-case group was $44,660 +/- $3645 compared to $22,360 +/- $3331 for 1
      degree repair (p = 0.00001). CONCLUSIONS: The data from this review show that
      palliation alone generates HC similar to that from 1 degree infant repair of TOF,
      and total combined HC and LOS for palliation plus eventual repair of TOF (two
      stage approach) are significantly higher than from 1 degree repair. Furthermore,
      these data do not include additional costs for care delivered between palliation
      and repair (e.g., outpatient visits, cardiac catheterization, serial
      echocardiography). Although there may be occasions when a strategy using initial
      palliation followed by later repair may seem prudent, the cost is clearly higher
      and use of health care resources greater.

PMID- 9230820
TI  - Aortic valve replacement in the elderly. Risk factors and long-term results.
AB  - OBJECTIVE: The current study was undertaken to determine long-term results of
      aortic valve replacement (AVR) in the elderly, to ascertain predictors of poor
      outcome, and to assess quality of life. SUMMARY BACKGROUND DATA: Aortic valve
      replacement is the procedure of choice for elderly patients with aortic valve
      disease. The number of patients aged 70 and older requiring AVR continues to
      increase. However, controversy exists as to whether surgery devoted to this
      subset reflect a cost-effective approach to attaining a meaningful quality of
      life. METHODS: This study reviews data on 247 patients aged 70 to 89 years who
      underwent isolated AVR between 1980 and 1995; there were 126 men (51%) and 121
      women (49%). Follow-up was 97% complete (239/247 patients) for a total of 974.9
      patient-years. Mean age was 76.2 +/- 4.8 years. Operative mortality and actuarial
      survival were determined. Patient age, gender, symptoms, associated diseases,
      prior conditions, New York Health Association class congestive heart failure,
      native valve disease, prosthetic valve type, preoperative catheterization data,
      and early postoperative conditions were analyzed as possible predictors of
      outcome. Functional recovery was evaluated using the SF-36 quality assessment
      tool. RESULTS: Operative mortality was 6.1% (15/247). Multivariate logistic
      regression showed that poor left ventricular function and preoperative pacemaker
      insertion were independent predictors of early mortality. After surgery,
      infection was predictive of early mortality. Overall actuarial survival at 1, 5,
      and 10 years was 89.5 +/- 2% (198 patients at risk), 69.3 +/- 3.4% (89 patients
      at risk), and 41.2 +/- 6% (13 patients at risk), respectively. Cox proportional
      hazards model showed that chronic obstructive pulmonary disease and urgency of
      operation were independent predictors of poor long-term survival. Postoperative
      renal failure also was predictive of poor outcome. Using the SF-36 quality
      assessment tool, elderly patients who underwent AVR scored comparably to their
      age-matched population norms in seven of eight dimensions of overall health. The
      exception is mental health. CONCLUSIONS: Aortic valve replacement in the elderly
      can be performed with acceptable mortality. Significant preoperative risk factors
      for early mortality include poor left ventricular function and preoperative
      pacemaker insertion. Predictors of late mortality include chronic obstructive
      pulmonary disease and urgency of operation. These results stress the importance
      of operating on the elderly with aortic valve disease; both long-term survival
      and functional recovery are excellent.

PMID- 9230821
TI  - Minimally invasive coronary artery bypass grafting decreases hospital stay and
      cost.
AB  - OBJECTIVE: The authors performed a retrospective cost analysis for patients
      undergoing revascularization of their left anterior descending (LAD) coronary
      artery either by standard coronary artery bypass grafting (CABG), percutaneous
      transluminal coronary angioplasty (PTCA), or minimally invasive coronary artery
      bypass grafting (MICABG). SUMMARY BACKGROUND DATA: Minimally invasive CABG has
      become a safe and effective alternative treatment for single-vessel coronary
      artery disease. However, the acceptance of this procedure as a routine
      alternative for the treatment of coronary artery disease will depend on both long
      term graft patency rates as well as a competitive market cost. METHODS: The
      authors conducted a retrospective analysis of three patient groups undergoing LAD
      coronary revascularization from January 1995 to July 1996. Ten patients were
      selected randomly from this period after PTCA of an LAD lesion with or without
      stenting. Nine patients underwent standard CABG on cardiopulmonary bypass with a
      left internal mammary artery. Nine patients received MICABG via a limited left
      anterior thoracotomy and left internal mammary artery to LAD grafting without the
      use of cardiopulmonary bypass. RESULTS: Percutaneous transluminal coronary
      angioplasty (n = 10) was unsuccessful in two patients. One patient in the MICABG
      group (n = 9) was converted successfully to conventional CABG because of an
      intramyocardial LAD and dilated left ventricle. There was no operative morbidity
      or mortality in any group. Average length of stay postprocedure was decreased
      significantly for both the MICABG and PTCA groups when compared with that of
      conventional CABG (n = 9) (2.7 + 0.26, p = 0.009, and 2.6 + 0.54, p = 0.006, vs.
      4.8 + 0.46, respectively). Total hospital costs for the MICABG and PTCA groups
      were significantly less when compared with those of standard CABG ($10,129 +
      1104, p = 0.0028, and $9113 + 3,039, p = 0.0001, vs. $17,816 + 1043,
      respectively). There were no statistically significant differences between the
      MICABG and PTCA groups. CONCLUSIONS: The final role of minimally invasive CABG is
      unclear. This procedure is clearly cost effective when compared with that of PTCA
      and conventional CABG. The long-term patency rates for MICABG will determine its
      overall efficacy.

PMID- 9230822
TI  - Evaluation of endothelial cell changes 1 year after excimer laser in situ
      keratomileusis.
AB  - OBJECTIVE: To investigate changes in the human corneal endothelium after excimer
      laser in situ keratomileusis for the correction of high myopia. METHODS:
      Preoperative and serial postoperative specular microscopy of the central corneal
      endothelium was performed on 31 patients (45 eyes) (group A) who underwent laser
      in situ keratomileusis for the correction of myopia ranging from -8.25 to -18.50
      diopters. Twenty-one patients (30 eyes) were contact lens wearers (group B), and
      10 patients (15 eyes) had never worn contact lenses (group C). The central
      endothelium was analyzed for cell density, coefficient of variation in cell size,
      and hexagonality. The preoperative data were compared with those obtained 3, 6,
      and 12 months after surgery in all groups. RESULTS: In group A, the postoperative
      mean cell density increased significantly (2.3%) at 6-month follow-up (P = .04);
      the coefficient of variation decreased at all follow-ups (P < .001); and the
      percentage of hexagonal cells increased at all follow-ups (P < .05). In group B,
      there was a significant postoperative increase in cell density at the 3- (2.36%)
      and 6-month (3.74%) follow-ups (P < .05); the coefficient of variation decreased
      at all follow-ups (P < .001); and the hexagonality was also significantly higher
      at all follow-ups than it was before treatment (P < .05). In group C, no
      significant differences in mean cell density or morphometric indexes were found
      between preoperative and postoperative values. CONCLUSIONS: Laser in situ
      keratomileusis caused no damage to the central corneal endothelium. The
      postoperative improvements in endothelial cell density and morphometric indexes
      are related to postoperative discontinuation of contact lens use.

PMID- 9230823
TI  - A 1-year study of brimonidine twice daily in glaucoma and ocular hypertension. A
      controlled, randomized, multicenter clinical trial. Chronic Brimonidine Study
      Group.
AB  - OBJECTIVE: Brimonidin tartrate is a highly selective alpha 2-agonist. This study
      investigates the safety and efficacy of 0.2% brimonidine administered twice daily
      for 1 year in patients with glaucoma or ocular hypertension. METHODS: The study
      design was a multicenter, double-masked, randomized, parallel-group, active
      controlled comparison clinical trial. Subjects instilled 0.2% brimonidine or 0.5%
      timolol maleate twice daily for 12 months. Subjects were examined at baseline,
      week 1, and months 1, 2, 3, 6, 9, and 12. A subset of subjects was examined at
      week 2. RESULTS: Of 443 subjects enrolled in this study, 374 met the entry
      criteria; 186 received brimonidine and 188 received timolol. Brimonidine-treated
      subjects showed an overall mean peak reduction in intraocular pressure (IOP) of
      6.5 mm Hg; timolol-treated subjects had a mean peak reduction in IOP of 6.1 mm
      Hg. Brimonidine lowered mean peak IOP significantly more than timolol at week 2
      and month 3 (P < .03); no significant difference was observed between the groups
      for this variable at other visits throughout the 1-year course of the study. No
      evidence of tachyphylaxis was seen in either group. Allergy was seen in 9% of
      subjects treated with brimonidine. Dry mouth was more common in the brimonidine
      treated group than in the timolol-treated group (33.0% vs 19.4%), but complaints
      of burning and stinging were more common in the timolol-treated group (41.9%)
      than in the brimonidine-treated patients (28.1%). Headache, fatigue, and
      drowsiness were similar in the 2 groups. In general, the tolerance to medication
      was acceptable. CONCLUSIONS: Brimonidine is safe and effective in lowering IOP in
      glaucomatous eyes. Brimonidine provides a sustained long-term ocular hypotensive
      effect, is well tolerated, and has a low rate of allergic response.

PMID- 9230824
TI  - Daily cost of beta-adrenergic blocker therapy.
AB  - OBJECTIVE: To evaluate the daily cost of beta-blocker therapy among commercially
      available products. METHODS: Ten different beta-adrenergic blocker preparations,
      each in 10-mL bottles (except Timoptic-XE [Merck brand of timolol maleate gel
      forming solution], which was in a 5-mL bottle), were acquired from a local
      pharmacy. Each of 10 subjects dispensed 10 drops from each bottle onto an
      analytical scale. The mean drop volume for each preparation was then calculated.
      The fill volume of each bottle and the amount of each medicine that was wasted
      upon dispensing also were determined. Additionally, 60 pharmacies in the United
      States were randomly chosen to determine the average cost of each preparation
      studied. Based on all data obtained, an average daily cost of each medicine was
      calculated. RESULTS: The generic formulation of timolol maleate (Falcon) ($0.55)
      and Betimol (Ciba Vision Ophthalmics brand of timolol hemihydrate) ($0.57)
      demonstrated the lowest cost per day of therapy. In contrast, Betoptic-S (Alcon
      brand of betaxolol hydrochloride) ($1.60) and Betagan (Allergan brand of
      levobunonol hydrochloride) ($1.35) had the highest daily cost of therapy.
      Ocupress (Otsuka America brand of carteolol hydrochloride) had the smallest drop
      volume (31 microL) and Timoptic-XE had the highest (49 microL). Most preparations
      were close to their stated bottle fill volume. The amount of wasted medicine
      varied and was least with Ocupress (27%) and greatest with Betoptic-S (54%). The
      mean pharmacy price for a 10-mL bottle was lowest for OptiPranolol (Bausch & Lomb
      brand of metipranolol) ($25.51) and Betimol ($28.28); Betoptic-S ($44.80) and
      Betagan ($43.67) were the most expensive. CONCLUSION: Although all commercially
      available beta-adrenergic blockers effectively lower intraocular pressure, one
      differential factor between medicines is cost, which may be influenced by the
      price at the pharmacy, volume of medication per bottle, drop size, and medicine
      wastage.

PMID- 9230825
TI  - Latanoprost and physostigmine have mostly additive ocular hypotensive effects in
      human eyes.
AB  - OBJECTIVE: To investigate if a pronounced ciliary muscle contraction, induced by
      physostigmine salicylate, can abolish the ocular hypotensive effect of
      latanoprost, a prostaglandin analogue, via inhibition of the uveoscleral outflow.
      DESIGN: A randomized, crossover study that was double-masked for latanoprost.
      Physostigmine was the second factor in a 2(2) factorial experiment. PARTICIPANTS:
      A total of 20 male and female healthy volunteers (median age, 25 years; age
      range, 17-30 years). INTERVENTIONS: Between 7 AM and 7 PM, 1 drop of
      physostigmine salicylate (8 mg/mL) was instilled in 1 eye every other hour. At 8
      AM, 1 drop of either latanoprost (50 mg/L) or placebo was instilled in both eyes.
      This protocol was repeated a second time with latanoprost administered to
      previously placebo-treated eyes and vice versa. MAIN OUTCOME MEASURES:
      Intraocular pressure differences were measured with Goldmann applanation
      tonometry hourly for 13 hours. RESULTS: Latanoprost reduced the intraocular
      pressure significantly at 3 to 12 hours after application with a maximal effect
      at 8 hours after the administration of the dose. The reduction that was obtained
      with physostigmine administered every other hour was more pronounced, was
      observed at 1 hour after the administration of the first dose, and increased
      throughout the day. A significant interaction was seen between 3 and 6 PM (i.e.,
      at 7-10 hours after application of latanoprost). CONCLUSIONS: Latanoprost and
      physostigmine have a mainly additive ocular hypotensive effect. Thus, high doses
      of physostigmine did not abolish the eye pressure-lowering effect of latanoprost,
      but some interaction was seen at low intraocular pressures. It was concluded that
      any mechanical effect on the uveoscleral flow achieved with physostigmine is
      short-lasting compared with the effect obtained with latanoprost, and that
      latanoprost and miotics can be combined.

PMID- 9230826
TI  - Interferon alfa-2a is ineffective for patients with choroidal neovascularization
      secondary to age-related macular degeneration. Results of a prospective
      randomized placebo-controlled clinical trial. Pharmacological Therapy for Macular
      Degeneration Study Group.
AB  - BACKGROUND: Interferon alfa-2a has been shown to be effective as an
      antiangiogenic agent for several systemic human angiogenic disorders and has
      shown antiangiogenic activity in the laboratory. OBJECTIVE: To evaluate the
      safety and efficacy of interferon alfa-2a for the treatment of choroidal
      neovascularization secondary to age-related macular degeneration. METHODS: A
      randomized, placebo-controlled, parallel, multicenter double-blind trial was
      performed at 45 ophthalmic centers worldwide. Four hundred eighty-one patients
      were randomly assigned to 4 treatment groups: placebo or interferon alfa-2a
      (Roferon-A), 1.5, 3.0, or 6.0 million international units (MIU). Visual acuity
      testing, clinical examination, fluorescein angiography, and indocyanine green
      angiography were evaluated, with the primary end point being a comparison of the
      number of patients who experienced a loss of 3 lines or more of vision at 1 year.
      RESULTS: At 52 weeks, 40 (38%; 95% confidence interval, 29%-48%) of 105 placebo
      treated patients had lost at least 3 lines of vision (with 12% unavailable for
      follow-up), compared with 142 (50%; 95% confidence interval, 44%-55%) of 286 in
      the 3 active treatment groups combined. The difference in proportions was not
      statistically significant. However, a pairwise comparison of these proportions
      for the placebo group vs the group that received interferon alfa-2a, 6 MIU (with
      26% unavailable for follow-up), showed a statistically significant difference in
      favor of the placebo group (P = .02) and a nearly significant difference for the
      placebo vs the 1.5-MIU group (P = .05) (with 16% unavailable for follow-up),
      again favoring the placebo group. The 3-MIU group (with 22% unavailable for
      follow-up) did not show a statistically significant difference in pairwise
      comparison (P = .48), suggesting that a dose-response relationship was not
      evident. CONCLUSION: Interferon alfa-2a provides no benefit as a treatment for
      choroidal neovascularization secondary to age-related macular degeneration and
      may be associated with a poorer visual outcome when given at a dose of 6 MIU.
      However, the absence of a clear dose-response relationship raises the possibility
      that the observed differences result from chance.

PMID- 9230827
TI  - Subretinal fibrosis in diabetic macular edema. ETDRS report 23. Early Treatment
      Diabetic Retinopathy Study Research Group.
AB  - OBJECTIVE: To describe the characteristics of and risk factors for subretinal
      fibrosis (SRF) in patients with diabetic macular edema. PATIENTS AND METHODS: A
      total of 109 eyes (in 96 persons) with SRF, defined as a mound or sheet of gray
      to white tissue beneath the retina at or near the center of the macula, were
      identified during the Early Treatment Diabetic Retinopathy Study, which is a
      randomized clinical trial of photocoagulation and aspirin treatment in patients
      with mild to severe nonproliferative or early proliferative diabetic retinopathy.
      The patients and the ocular characteristics of these 109 eyes, all of which had
      clinically significant macular edema, were compared with those of 5653 eyes in
      which clinically significant macular edema, but not SRF, was observed during the
      trial. RESULTS: In 9 of 109 eyes, the development of SRF may have been directly
      related to focal photocoagulation. Seventy-four percent of the eyes in which SRF
      developed had very severe hard exudates in the macula prior to the development of
      SRF, while this level of hard exudates was seen in only 2.5% of the eyes with
      clinically significant macular edema in which SRF did not develop (P < .001). Of
      the 264 eyes with this level of hard exudates at baseline (n = 29) or during
      follow-up (n = 235), SRF developed in 30.7% of the eyes, while this complication
      developed in only 0.05% of 5498 eyes with clinically significant macular edema
      without this level of hard exudates. CONCLUSIONS: Subretinal fibrosis is an
      infrequent complication of diabetic macular edema. Although it has been reported
      to be associated with photocoagulation burn intensity, in only 9 of 109 eyes in
      which SRF developed was it located adjacent to a photocoagulation-related scar
      (among 4823 eyes that received focal photocoagulation for treatment of macular
      edema). The strongest risk factor for the development of SRF is very severe hard
      exudate.

PMID- 9230828
TI  - Familial internal limiting membrane dystrophy. A new sheen retinal dystrophy.
AB  - OBJECTIVE: To describe the clinicopathologic features of a previously unreported
      retinal dystrophy. METHODS: Fourteen members of a single family were examined.
      The medical records of 2 additional family members were reviewed. Pathologic
      examination was performed on 2 eyes of 1 affected patient. RESULTS: Five
      individuals were identified with a retinal dystrophy characterized by a
      glistening inner retinal surface throughout the posterior pole. Visual loss
      occurred in 3 affected patients in later life owing to superficial polycystic
      retinal edema and retinal folds. Electroretinographic testing revealed a
      selective diminution of the b wave. Pathologic examination revealed an abnormal
      internal limiting membrane with schisis cavities in the inner retina. Endothelial
      cell swelling, pericyte degeneration, and basement membrane thickening were
      present in retinal capillaries. CONCLUSIONS: A previously unreported sheen
      retinal dystrophy is described. Pedigree analysis suggests an autosomal dominant
      mode of inheritance. A primary defect in Muller cells is the suspected, but
      unproved, cause. No effective treatment for the associated visual loss is known.
      The term familial internal limiting membrane dystrophy is proposed to describe
      this condition.

PMID- 9230829
TI  - Mortality in patients with small choroidal melanoma. COMS report no. 4. The
      Collaborative Ocular Melanoma Study Group.
AB  - OBJECTIVE: To describe the clinical characteristics and survival experience of a
      prospectively followed up group of patients with small choroidal melanoma.
      METHODS: The Collaborative Ocular Melanoma Study (COMS) is a set of clinical
      trials designed to compare the role of radiotherapy and enucleation in the
      treatment of medium and large-size choroidal melanoma. From December 1986 to
      August 1989, patients with small choroidal melanoma, not large enough to be
      eligible for the COMS clinical trials, were offered participation in a
      nonrandomized prospective follow-up study. Small choroidal melanomas were defined
      as 1.0 to 3.0 mm in apical height and at least 5.0 mm in basal diameter. A total
      of 204 patients were enrolled in the study. Patients were followed up annually
      through August 1989. Two additional assessments of treatment status and mortality
      were conducted in 1993-1994 and 1995-1996. The median length of follow-up was 92
      months. Eight percent of patients were treated at the time of study enrollment
      and an additional 33% were treated during follow-up. RESULTS: Twenty-seven
      patients have died; 6 deaths were reported by the clinical center as due to
      metastatic melanoma. The Kaplan-Meier estimate of 5-year all-cause mortality was
      6.0% (95% confidence interval, 2.7%-9.3%) and 8-year all-cause mortality was
      14.9% (95% confidence interval, 9.6%-20.2%). CONCLUSIONS: Otherwise healthy
      patients, average age of 60 years, without a previous diagnosis of malignant
      disease who have small choroidal lesions judged to be melanoma have a low risk of
      dying within 5 years.

PMID- 9230830
TI  - Clear cell differentiation in choroidal melanoma. COMS report no. 8.
      Collaborative Ocular Melanoma Study Group.
AB  - OBJECTIVE: To describe 2 enucleated eyes of patients enrolled in the
      Collaborative Ocular Melanoma Study that contained primary choroidal melanoma
      with clear cell features. METHODS: During a 9-year period, 1493 eyes enucleated
      as part of the Collaborative Ocular Melanoma Study routinely processed for
      histologic examination were evaluated by the pathology review committee (H.E.G,
      D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were
      identified and immunostained for S100 protein and HMB 45. Portions of the tumors
      were processed for electron microscopic examination. RESULTS: Results of electron
      microscopic examination of both tumors displayed malignant melanoma (mixed cell
      type with many malignant cells with clear cytoplasm). The cytoplasm of the clear
      cells stained with periodic acid-Schiff and failed to stain when pretreated with
      diastase. Results of immunohistochemical stains in both tumors were positive for
      S100 protein and HMB 45 in the tumor cells. Results of electron microscopic
      examination showed that the cytoplasm of the clear cells contained scattered
      glycogen granules, premelanosomes, and melanosomes. CONCLUSION: These cases
      represent a clear cell variant of malignant melanoma of the choroid. This tumor
      should not be confused with metastatic clear cell carcinoma to the choroid.

PMID- 9230831
TI  - Interaction between infrared radiation and vitreous substitutes.
AB  - OBJECTIVE: To characterize the interaction between midintrared radiation of
      cutting lasers used or proposed for vitreoretinal surgery and fluid vitreous
      substitutes commonly used in vitreoretinal surgery. METHODS: Optical
      transmittance of vitreous substitutes was measured with a double-beam
      spectrophotometer. Measurements were performed in a wide spectral range of
      infrared radiation, including the 2120-nm wavelength of the holmium-YAG laser and
      the water absorption peaks at 1440, 1930, and 2940 nm. RESULTS: The wavelengths
      considered have a penetration depth varying from 410 to 1 microns in Ringer's
      solution, balanced salt citrate-buffered solution, balanced salt bicarbonated
      buffered solution, hyaluronate sodium, and hydroxypropyl methylcellulose
      ophthalmic solution, from 2000 to 13 mm in perfluorocarbon liquid, and from 52 to
      2.5 mm in silicone and fluorosilicone oils. CONCLUSIONS: Midinfrared optical
      radiation exhibits dramatic differences of penetration depth in different
      vitreous substitutes. High-absorbing liquids should be used mainly with contact
      laser procedures and could provide a shield for remote structures. Low-absorption
      vitreous substitutes allow noncontact laser surgical procedures, but they also
      may cause direct optical damage to remote tissues. The knowledge of wavelength
      transmittance of vitreous substitutes is necessary to evaluate and optimize the
      efficacy and safety of cutting laser sources.

PMID- 9230832
TI  - Assessment of the phenotypic range seen in Doyne honeycomb retinal dystrophy.
AB  - OBJECTIVE: Using molecular genetics as the basis for diagnosis, to assess the
      phenotype in the family originally described as having dominantly inherited Doyne
      honeycomb retinal dystrophy (DHRD) linked to chromosome 2p16. DESIGN: Clinical
      examination including fluorescein angiography was undertaken in 107 family
      members. Nine affected patients underwent electroretinography, perimetry, dark
      adaptometry, color-contrast sensitivity measurement, and autofluorescent fundus
      imaging. PATIENTS: The disease-associated haplotype used to allocate disease
      status was based on our further refinement of the DHRD locus to between loci
      D2S2739 and D2S378. The study identified 50 affected patients. In addition,
      previously published information on a further 8 individuals was used. The study
      population represented 6 generations of a 9-generation pedigree. RESULTS: Three
      types of deposits were seen: large, soft drusen at the macula and abutting the
      optic nerve head; small, hard deposits that in some patients radiated from the
      macula; and autofluorescent deposits. Most younger affected individuals exhibited
      small hard drusen only at the macula and had normal visual function. Information
      on 2 patients suggested that DHRD can be a cause of childhood-onset blindness.
      Advanced disease was associated with severe visual loss and posterior pole
      atrophy without signs of drusen. Advanced age was not invariably associated with
      severe visual loss. CONCLUSIONS: Previously identified characteristics of DHRD
      were confirmed and new features identified. Contrary to previous reports, the
      constancy and severity of radial (basal laminar) drusen seen clinically are the
      only features that can be used to differentiate between DHRD and malattia
      leventinese. The highly variable phenotype suggests that the influence of the
      DHRD-mutant gene may be modulated by other genetic and/or environmental factors.

PMID- 9230833
TI  - Prostaglandins and cholinomimetics.

PMID- 9230834
TI  - Cost of beta-blocker therapy.

PMID- 9230835
TI  - We are very spoiled.

PMID- 9230836
TI  - Should rates of cataract surgery vary by insurance status?

PMID- 9230837
TI  - Iron overload is a risk factor for zygomycosis.
AB  - Well-recognized risk factors for zygomycosis include diabetic ketoacidosis,
      immunocompromise, and deferoxamine therapy for iron or aluminum overload, usually
      in patients undergoing kidney dialysis. We report a case of fatal nasal-orbital
      cerebral zygomycosis in an 82-year-old man with known myelodysplasia and well
      controlled diabetes. He was not receiving deferoxamine. Despite radical surgery
      and amphotericin B therapy, he died; primary hemochromatosis with gross iron
      overload was found post mortem. Experimental evidence suggests iron overload
      without deferoxamine therapy may be a risk factor for zygomycosis; the findings
      in this case would support this hypothesis.

PMID- 9230838
TI  - Giant epidermoid involving 3 cranial bones.
AB  - We describe a patient with an incidental finding of an expansile osteolytic
      lesion centered in the sphenoid involving 3 cranial bones-frontal, temporal, and
      sphenoid-and invading the brain parenchyma and orbit. Biopsy demonstrated an
      epidermoid. The lesion was excised through frontotemporal craniotomy. Despite the
      benign nature of the tumor, the epidermoid had a destructive pattern of growth.
      Complete resection was needed to adequately address the inflammatory mass effect
      of the large lesion.

PMID- 9230839
TI  - Catastrophic complications of automated lamellar keratoplasty.

PMID- 9230840
TI  - Neurotrophic and anhidrotic keratopathy treated with substance P and insulinlike
      growth factor 1.

PMID- 9230841
TI  - Subretinal fluid associated with membranoproliferative glomerulonephritis type 2.

PMID- 9230842
TI  - Surgical treatment of a macular hole secondary to accidental laser burn.

PMID- 9230843
TI  - Restrictive strabismus after ocular surgery for retinitis pigmentosa in Cuba.

PMID- 9230844
TI  - Use of galeal or pericranial flaps for reconstruction or orbital and eyelid
      defects.
AB  - The use of galeal or pericranial flaps for craniofacial reconstruction is well
      recognized. The excellent blood supply of the flap permits vascularized support
      for skin, bone, or cartilage grafts in otherwise unsatisfactory recipient sites.
      The pericranial flap was used in 1 patient with a large orbital bony defect and
      the galeopericranial flap was used in 3 patients with various periocular defects
      produced by trauma or following tumor extirpation. In the case of an orbital
      defect induced by chronic cocaine abuse, the pericranial flap successfully
      sequestered the orbit from the nasal cavity while providing support for the
      globe. In 3 of the 4 cases involving eyelid reconstruction, the galeopericranial
      flap served a dual function in providing vascular supply to the underlying free
      tarsal graft and to the overlying free skin graft. This tissue flap is analogous
      to a median forehead flap, except skin is not transposed and a second-stage inset
      revision is not required.

PMID- 9230845
TI  - Epithelial rejection rings.

PMID- 9230846
TI  - Growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO syndrome)
      with congenital glaucoma.

PMID- 9230847
TI  - Retinal artery obstruction in young patients.

PMID- 9230848
TI  - Nonarteritic anterior ischemic optic neuropathy: role of nocturnal arterial
      hypotension.

PMID- 9230849
TI  - Smoking is also associated with age-related macular degeneration in persons aged
      85 years and older: The Rotterdam Study.

PMID- 9230850
TI  - The formation of crystals in ganciclovir used for intraocular injection.

PMID- 9230851
TI  - Surgery in Egypt.
AB  - The history of medicine can never be complete without referral to ancient
      Egyptian medicine. Imhotep has been identified as the god of medicine. There are
      13 faculties of medicine in Egypt; the oldest is the Kasr El Aini Faculty, which
      started in 1925. We review undergraduate and postgraduate education in Egypt. The
      Egyptian Society of Surgeons organizes the scientific surgical activities.
      Schistosomiasis is a national health problem. Health care is provided by many
      types of hospitals, including university, teaching, Ministry of Public Health,
      military, and private hospitals.

PMID- 9230852
TI  - Multiple organ failure, multiple organ dysfunction syndrome, and systemic
      inflammatory response syndrome. Why no magic bullets?
AB  - The concept of multiple organ failure and related abnormalities was first
      developed in the 1970s. Multiple organ failure became evident when the support
      systems in intensive care units were able to keep patients alive long enough for
      multiple organ problems to develop in them. The high mortality of patients with
      multiple organ failure provided a focus for the problems that ultimately led to
      death for many patients in the intensive care unit. The frequency of infection,
      sepsis, or inflammation in producing multiple organ failure led to clinical
      trials of so-called magic bullets for the treatment of patients with sepsis.
      These trials have had either limited success or negative results, despite
      considerable evidence for efficacy or protection by such agents in experimental
      animals and in studies of normal human volunteers. I believe a major reason for
      these negative results has been the use of general entry criteria for the trials
      rather than the treatment of specific diseases or injuries.

PMID- 9230853
TI  - Laparoscopic vs open appendectomy. Prospective randomized study of outcomes.
AB  - OBJECTIVE: To compare open appendectomy (OA) with laparoscopic appendectomy (LA)
      for length of the operation, complications, postoperative pain control, length of
      hospitalization, postdischarge recovery time, and hospital charges. DESIGN:
      Prospective randomized clinical trial of patients with acute appendicitis.
      SETTING: Tertiary care, urban teaching hospital. PATIENTS: A population-based
      sample of patients (aged > or = 12 years; weight, > 49.7 kg) admitted to a
      surgical teaching service with a clinical diagnosis of acute appendicitis.
      Patients were prospectively randomized to either OA or LA during a 20-month
      period (from April 1, 1994, to December 31, 1995). Fifty-seven patients were
      initially enrolled in the study; 7 did not complete the study because of a
      protocol violation. All remaining patients completed the study, including
      postdischarge follow-up. INTERVENTIONS: Two (7.4%) of the 27 patients in the LA
      group required conversion to OA because of technical difficulties. One patient
      (in the OA group) underwent a second surgical procedure for drainage of a pelvic
      abscess. Three patients (in the LA group) required second surgical procedures.
      For analysis, no crossovers were allowed and all patients remained in their
      originally randomized group. MAIN OUTCOME MEASURES: Length of the operation,
      intraoperative and postoperative complications, postoperative pain control,
      length of hospitalization, postdischarge recovery time, and hospital charges.
      RESULTS: Fifty patients (19 women and 31 men) were examined. Twenty-seven
      patients underwent LA, 2 requiring conversion to an OA. Twenty-three patients
      underwent an OA. Patient demographics were similar between groups. Statistical
      differences between the 2 groups were found for (1) length of the operation
      (median, 81.7 vs 66.8 minutes, LA vs OA groups: P < .002), (2) operating room
      charges (median, $3191 vs $1514, LA vs OA group; P < .001), and (3) total
      hospital charges (median, $5430 vs $3673, LA vs OA group; P < .001). No
      statistical differences between the 2 groups were found for (1) length of
      hospitalization (median, 1.1 vs 1.2 days, LA vs OA group), (2) pain control
      (mean, 4 vs 3.7 of 10 [0 indicates least pain; 10, most pain], LA vs OA group),
      (3) recovery time (time necessary before returning to work or school) (median,
      14.0 days for both groups), and (4) complications (5 vs 1, LA vs OA group).
      CONCLUSIONS: Laparoscopic appendectomies and OAs are comparable for
      complications, postoperative pain control, length of hospitalization, and
      recovery time. Patients who underwent an OA had a shorter operative time and
      lower operating room and hospital charges. Laparoscopic appendectomy does not
      offer any proved benefits compared with the open approach for the routine patient
      with acute appendicitis.

PMID- 9230854
TI  - Abdominal operations after lung transplantation. Indications and outcome.
AB  - OBJECTIVE: To assess the outcomes of abdominal operations in patients with lung
      transplants and identify adverse risk factors. DESIGN: Matched cohort study.
      SETTING: University referral center. PARTICIPANTS: Twelve lung transplant
      recipients who required abdominal operations (hereafter referred to as case
      patients) and 12 age-, sex-, and pulmonary diagnosis-matched lung transplant
      recipients who had not undergone an abdominal procedure (hereafter referred to as
      control patients). INTERVENTIONS: Elective abdominal operations including
      laparoscopic cholecystectomies (n = 5), laparoscopic repair of a colovaginal
      fistula (n = 1), and open colectomy for a benign colovesical fistula (n = 1) and
      urgent operations including bowel resections (n = 3), subtotal pancreatectomy (n
      = 1), and hepatorrhaphy for an iatrogenic liver injury (n = 1). MAIN OUTCOME
      MEASURES: Morbidity and mortality. RESULTS: Abdominal operations were performed
      in 12 (11%) of the patients undergoing lung transplantation at the university
      referral center since 1987, with an associated mortality rate of 25%. Morbidity
      and mortality rates of electively performed procedures were 28% and 14%,
      respectively. An urgent indication for abdominal procedure was associated with
      100% morbidity and 40% mortality. Compared with a matched group of 12 control
      patients, the long-term survival of the case patients was reduced (18% vs 64% at
      4 years). Case patients undergoing an abdominal procedure in the
      posttransplantation period tended to have a higher prevalence of previous
      rejection (67% vs 25%), a higher perioperative steroid dosage (53 mg/d vs 36
      mg/d), and a significantly lower posttransplantational forced expiratory volume
      in 1 second (FEV1, 1.23 L vs 1.91 L; P < .05). CONCLUSIONS: Elective abdominal
      operations are relatively safe in properly prepared lung transplant recipients.
      However, laparotomy for urgent surgical conditions is associated with increased
      morbidity and mortality rates caused in part by the magnitude of the abdominal
      operation and influenced by the status of the lung transplant as manifested by
      previous rejection episodes, perioperative steroid dosages, and FEV1 values.

PMID- 9230855
TI  - Nissen fundoplication prevents shortening of the sphincter during gastric
      distention.
AB  - OBJECTIVE: To determine the dynamic effects of a Nissen fundoplication on a
      volume-stressed lower esophageal sphincter (LES). DESIGN: Before and after
      experimental study in 10 baboons. SETTING: University animal research unit.
      INTERVENTIONS: Continuous manometric evaluation of the esophagus, cardia, and
      stomach during distention of the stomach with water. Slow motorized pull-through
      of the LES after each successive intragastric increment of 50 mL of water. Tests
      were performed again after a Nissen fundoplication. MAIN OUTCOME MEASURES: Lower
      esophageal sphincter length and frequency of common cavity episodes after each
      volume increment. The pressure and intragastric volume at the yield point are
      defined as the point of permanent loss of the gastroesophageal pressure gradient.
      RESULTS: Gastric distention of the stomach with water resulted in a progressive
      decrease in LES length and competency. The median +/- interquartile range LES
      length decreased by 1.5 +/- 0.3 mm for every 1-mm Hg increase in gastric pressure
      before fundoplication and by 0.2 +/- 0.1 mm after fundoplication (P < .02). With
      gastric distention there was an indirect correlation between the degree of LES
      length and the frequency of reflux episodes (r = -0.70). This correlation was
      abolished by a Nissen fundoplication (r = -0.31). The median +/- interquartile
      range frequency of common cavity episodes (2.19 +/- 2.05 episodes per minute)
      before fundoplication decreased significantly (P < .001) to 0 +/- 0.59 episodes
      per minute after fundoplication. The median +/- interquartile range yield
      pressure (13 +/- 9 mm Hg) and yield volume (825 +/- 855 mL) were significantly (P
      < .01) improved after Nissen fundoplication to 39 +/- 36 mm Hg and 1250 +/- 750
      mL, respectively. CONCLUSION: By preventing sphincter shortening, a Nissen
      fundoplication improves competency of the LES to progressive degrees of gastric
      distention.

PMID- 9230856
TI  - Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett
      esophagus.
AB  - OBJECTIVE: To evaluate the alteration of apoptosis in the esophageal epithelium
      during the esophagitis-Barrett esophagus-adenocarcinoma sequence. DESIGN:
      Archival tissue samples of 85 lesions in 58 cases were used. The lesions
      represented 7 groups: normal esophagus (n = 10), reflux esophagitis (n = 12),
      Barrett metaplasia (n = 21), Barrett low-grade dysplasia (n = 17), Barrett high
      grade dysplasia (n = 5), well- or moderately differentiated adenocarcinoma (n =
      10), and poorly differentiated adenocarcinoma (n = 10). Apoptotic cells with
      fragmented DNA were detected by the terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL)
      method. Monoclonal antibodies against bcl-2 protein were applied using the avidin
      biotin complex immunoperoxidase method. RESULTS: The esophagitis group showed
      many apoptotic cells on the epithelial surface; in the other groups, few
      apoptotic cells were seen. Weak bcl-2 expression was seen in the basal cells in
      normal subjects and those with esophagitis. There was overexpression of bcl-2 in
      72% of Barrett metaplasia, 100% of Barrett low-grade dysplasia, 25% of Barrett
      high-grade dysplasia, 40% of well- or moderately differentiated adenocarcinoma,
      and 20% of poorly differentiated adenocarcinoma. CONCLUSIONS: Increased apoptosis
      in reflux esophagitis may be a protective mechanism counteracting increased
      proliferation. Inhibition of apoptosis by overexpression of bcl-2 protein occurs
      early in the dysplasia-carcinoma sequence of Barrett esophagus. The resulting
      prolongation of cell survival may promote neoplastic progression. Despite the
      absence of apoptosis, bcl-2 was not widely overexpressed in Barrett high-grade
      dysplasia and adenocarcinoma, suggesting that cells acquire other ways of
      avoiding apoptosis as malignancy appears.

PMID- 9230857
TI  - Advances in critical care monitoring.
AB  - A critical evaluation of monitoring in critical illness must recognize first that
      there are many different types of monitoring that may take place, and that each
      type of monitor may be evaluated appropriately by different standards. Monitoring
      may occur with imaging devices, analyzers that require the permanent removal of
      tissue or fluid for analysis, or monitors that observe physiology with either
      invasive or noninvasive methods without requiring an ex vivo sample.

PMID- 9230858
TI  - How accurate is computed tomography in predicting the real size of adrenal
      tumors? A retrospective study.
AB  - BACKGROUND: The ability to accurately assess tumor size is an important
      consideration during the preoperative evaluation of adrenal tumors, particularly
      solid nonfunctioning masses (incidentalomas or adrenalomas). Does the
      histological size of the adrenal tumor correspond to the preoperative computed
      tomography (CT)-estimated size? OBJECTIVE: To evaluate the accuracy of CT in
      predicting the real size of adrenal tumors. DESIGN: Retrospective review of all
      clinical records of patients who underwent adrenalectomy from 1984 through 1995.
      The mean tumor size reported from CT examinations was compared with the
      corresponding size obtained from the pathology reports and the statistical
      difference was evaluated. SETTING: University and private hospitals in Athens,
      Greece. PATIENTS: Seventy-six patients who underwent adrenalectomy for various
      adrenal diseases and who met strict entry criteria. RESULTS: For the entire
      population, the mean diameter of the tumors was estimated (CT reports) at 4.64
      cm, but the real value (pathology reports) was 5.96 cm (P < .001). The
      underestimation held true for all of the studied subgroups that were defined by
      the different proposed cutoffs for malignancy. Three patients were incidentally
      found to have adrenal cancer, with the tumors measuring from 2.6 to 2.9 cm on CT.
      In addition, 4 pheochromocytomas were clinically and laboratory "silent" at the
      time of their discovery. The regression line (y = 0.85 + 1.09x) relating CT
      estimated and histological tumor size was linear (r = 0.90, P < .001).
      CONCLUSIONS: Computed tomography underestimates the real size of adrenal tumors.
      The CT-estimated value should be corrected accordingly to obtain the real size.
      The size of an adrenal tumor, even when corrected, cannot predict the tumor's
      clinical behavior in many cases. Surgeons should always cautiously interpret the
      proposed diagnostic cutoffs, especially when considering surgical or conservative
      management of small nonfunctioning adrenal tumors.

PMID- 9230859
TI  - Safety, efficacy, and cost of pancreaticoduodenal resection in a specialized
      center based at a community hospital.
AB  - OBJECTIVE: To determine whether pancreaticoduodenal resection (PDR) for benign
      and malignant disease can be performed safely, efficiently, and economically at a
      50-bed community hospital. DESIGN: Retrospective review of 39 consecutive PDRs
      performed in an 18-month period. Indications for surgery, length of hospital
      stay, complications, and patient charges were analyzed. SETTING: A suburban 50
      bed community hospital. PATIENTS: Thirty-nine patients (15 male and 24 female)
      referred for PDR for benign and malignant disease. MAIN OUTCOME MEASURES:
      Mortality and morbidity rates, length of hospital stay, care, and cost. RESULTS:
      Of 39 patients who underwent PDRs, 1 patient (2.6%) died of myocardial infarct.
      Intraoperative blood transfusions were required by 3 patients (8%). The mean
      postoperative hospital stay was 11 days. Twenty-four patients (62%) were
      discharged by day 11. Fifteen patients (38%) were hospitalized 11 to 24 days.
      Complications in 10 patients (28%) included pancreatic or biliary fistula (n =
      6), upper gastrointestinal tract bleeding (n = 1), partial wound dehiscence (n =
      1), bacteremia (n = 1), and pneumonia (n = 1). No patient required reoperation.
      Three patients were rehospitalized within 1 month. Mean patient charges were
      $21,864, and mean reimbursements were $19,669. CONCLUSIONS: Pancreaticoduodenal
      resection can be accomplished with low morbidity and mortality rates and a short
      stay at a community hospital. Thorough preoperative investigations to exclude
      unresectable lesions must precede every PDR for malignant disease. Mortality and
      morbidity rates in this series were similar to those for patients with similar
      diagnoses who were operated on in academic centers. Cost for and length of
      hospital stay of these 39 patients were significantly lower than those in other
      reported series.

PMID- 9230860
TI  - Prospective evaluation of vacuum pleural drainage after thoracotomy in patients
      with esophageal carcinoma.
AB  - OBJECTIVE: To evaluate the safety and efficacy of vacuum pleural drainage systems
      in selected patients. DESIGN: Prospective nonrandomized study. SETTING: Division
      of Upper Gastrointestinal Surgery at a tertiary care center. PATIENTS AND
      INTERVENTION: Between January 1, 1995, and December 31, 1995, 32 patients
      underwent a right-sided posterolateral thoracotomy for the resection of
      esophageal carcinoma. A vacuum drain was employed in 21 patients (group 1) and an
      under-water drain in 11 patients (group 2). The selection of patients for vacuum
      drainage was based on minimal pleural adhesions and technical ease of the
      operation. MAIN OUTCOME MEASURE: Data on drainage efficiency, total drainage
      output and duration of the drain being left in situ, and postoperative pulmonary
      complications were analyzed. RESULTS: The median total drainage outputs were 1280
      mL and 1230 mL (P = .92, Mann-Whitney U test) in groups 1 and 2, respectively,
      and the median duration of chest drains being left in situ was 7 days and 6 days
      (P = .11, Mann-Whitney U test) in groups 1 and 2, respectively. Postoperative
      pulmonary complications occurred in 5 patients (24%) enrolled in group 1 and 5
      patients (45%) enrolled in group 2 (P = .09, Fisher exact test). No hospital
      mortality was reported during the study. CONCLUSION: The vacuum drain has proved
      to be as safe and efficient as the traditional underwater drain, imposing less
      discomfort and allowing early mobilization. The vacuum drain is, therefore,
      recommended in selected patients undergoing thoracotomy for esophageal resection.

PMID- 9230861
TI  - Transforming growth factor beta 3 (TGF beta 3) accelerates wound healing without
      alteration of scar prominence. Histologic and competitive reverse-transcription
      polymerase chain reaction studies.
AB  - BACKGROUND: Transforming growth factor (TGF) beta 3 is a new isoform of the TGF
      beta superfamily and is presumed to play an important role in wound repair and
      scarring. OBJECTIVE: To examine the effects of TGF beta 3 on wound healing and on
      reducing scarring. DESIGN AND INTERVENTIONS: Dermal ulcers were created on the
      ears of 75 anesthetized young female rabbits. Either TGF beta 3 or vehicle was
      applied topically to the wounds. Wounds were bisected and analyzed histologically
      at postwounding day 7. A second group of wounds was treated with topical TGF beta
      3 and TGF beta 2 or vehicle at days 0 and 3 and harvested at days 21 through 42
      as an excessive scarring model. The third group of wounds was treated with TGF
      beta 1, TGF beta 2, and TGF beta 3 and vehicle. The granulation tissue was
      harvested at day 7, and cellular RNA was extracted for performing competitive
      reverse-transcription polymerase chain reaction. MAIN OUTCOME MEASUREMENT: The
      amount of new epithelium and granulation tissue was measured in TGF beta 3- and
      vehicle-treated wounds. The hypertrophic index was calculated for scarring wounds
      treated with TGF beta 2 and TGF beta 3 or vehicle. Levels of TGF beta 1 messenger
      RNA were measured in those wounds that were treated with TGF beta 1, TGF beta 2,
      and TGF beta 3 and in their controls. RESULTS: The use of TGF beta 3 (0.3-0.75
      microgram per wound) increased granulation tissue formation by more than 100% (P
      < .005). Epithelialization showed a biphase, either increasing 30% (P < .04) or
      decreasing 25% (P < .001) dependent on dose. No significant difference in the
      hypertrophic index was noted in TGF beta 3-treated wounds compared with controls.
      Levels of TGF beta 1 messenger RNA increased (7.1- to 14.9-fold) in those wounds
      treated with TGF beta s compared with controls at day 7. CONCLUSIONS: Exogenous
      TGF beta 3 displays substantial vulnerary properties in wound healing and may be
      useful in treating nonhealing wounds. However, the observation that TGF beta 3
      can reduce scarring was not confirmed in this study, and the messenger RNA level
      in response to TGF beta 3 suggests that it behaves similarly to TGF beta 1.

PMID- 9230862
TI  - Laparoscopic-assisted resection of rectosigmoid carcinoma. Immediate and medium
      term results.
AB  - BACKGROUND: The technique of laparoscopic-assisted resection of colorectal
      carcinoma has been established. However, whether such a procedure is beneficial
      to patients is uncertain. OBJECTIVE: To review the immediate and medium-term
      results of laparoscopic-assisted resection in patients with rectosigmoid
      carcinoma. PATIENTS AND INTERVENTIONS: We attempted laparoscopic-assisted sigmoid
      colectomy or anterior resection in 50 patients with rectosigmoid carcinoma (ie,
      the study group). The results were compared with those of 50 matched patients who
      underwent conventional open resection in the immediate prelaparoscopic era (ie,
      the control group). RESULTS: The median follow-up times for the study and control
      groups were 32.8 and 39.1 months, respectively. The operating time was
      significantly longer (P < .001, Student t test), while the analgesic requirement
      was significantly less (P < .001, Mann-Whitney U test) and the duration of
      hospitalization was significantly shorter (P = .001, Mann-Whitney U test), in the
      study group than in the control group. The oncological clearance (ie, the number
      of lymph nodes removed and the distal resection margin), the complication rate,
      the disease-free rate, and the survival rate were comparable in the 2 groups.
      CONCLUSION: The immediate and medium-term results of laparoscopic-assisted
      resection of rectosigmoid carcinoma are promising.

PMID- 9230863
TI  - Comparing preincisional with postincisional bupivacaine infiltration in the
      management of postoperative pain.
AB  - OBJECTIVE: To determine if preemptive local anesthesia yields better
      postoperative pain control than infiltration of local anesthetic at the time of
      wound closure. DESIGN: Prospective, randomized trial. SETTING: Private community
      teaching hospital. PATIENTS: Two-hundred consecutive patients undergoing elective
      laparotomy were enrolled in the study between September 1993 and April 1995.
      Eighty-eight patients were excluded from the study for violation of protocol,
      leaving a total of 112 patients to be evaluated. Patients were divided into 2
      groups: preincisional (n = 52) and postincisional (n = 60). INTERVENTIONS:
      Patients in the preincisional group received 40 mL of 0.25% bupivacaine
      (Marcaine) 5 minutes before the incision; patients in the postincisional group
      received 40 mL of 0.25% bupivacaine immediately after approximation of the fascia
      and before closure of the skin. MAIN OUTCOME MEASURES: The control of the long
      term (3-day) postoperative pain in relationship to timing of local anesthetic
      given. RESULTS: Study groups were comparable for age, weight, sex, operative
      time, and length of incision. No significant difference in the amount of morphine
      used or subjective evaluation of pain was noted between the preincisional and the
      postincisional groups. CONCLUSIONS: Based on the theory of "dorsal horn
      hypersensitivity," several clinical trials have shown significant improvement in
      pain control with preincisional infiltration of local anesthetic. Our results
      indicate that pain was no better controlled with preincisional infiltration than
      with postincisional infiltration of bupivacaine, raising the question of the
      benefit of preemptive anesthesia at the local level in long-term postoperative
      care.

PMID- 9230864
TI  - Results of 1001 pancreatic resections for invasive ductal adenocarcinoma of the
      pancreas.
AB  - OBJECTIVE: To evaluate the recent results of pancreatic resection in patients
      with invasive ductal adenocarcinoma of the pancreas. DESIGN: Retrospective study.
      SETTING: Seventy-seven medical facilities belonging to the Japan Society of
      Pancreatic Surgery. PATIENTS: One thousand one patients who underwent a resection
      of the pancreas between January, 1, 1991, and December 31, 1994. MAIN OUTCOME
      MEASURES: Morbidity and survival after surgery for pancreatic cancer according to
      the modified TNM classification of the International Union Against Cancer.
      RESULTS: After pancreatic resection, the cumulative postoperative survival rates
      at 1 and 3 years were 44.5% and 10.3%, respectively. Patients with early-stage
      cancers had a more prolonged survival time, ie, the cumulative 3-year survival
      rates for patients with stage I or stage II cancers were 50.4% and 45.5%,
      respectively; the survival rates for patients with stage III and stage IVa and
      IVb cancers were 17.6%, 5.7%, and 0%, respectively. The survival rate for
      patients with N1 or N2 metastasis did not differ appreciably, and both groups had
      significantly better survival rates than patients with N3 metastasis (P < .001).
      A significant difference in the postoperative survival time of N1 metastasis was
      observed between patients with no lymph node dissection (mean survival, 326.4
      days) and patients who received a lymph node dissection (D1) (mean survival,
      478.2 days) (P < or = .01). CONCLUSIONS: The recent results of pancreatic
      resection for invasive ductal adenocarcinoma of the pancreas are generally
      unsatisfactory. Although the outcome of the patients with an N1 metastasis can be
      improved if they receive N1 lymph node dissection (D1), an extensive lymph node
      dissection in advanced cancers does not necessarily produce a favorable
      prognosis.

PMID- 9230865
TI  - Spinal cord injury. A preventable public burden.
AB  - BACKGROUND: Spinal cord injury (SCI) is a devastating occurrence with important
      consequences for the individual and society. Previous studies have documented the
      epidemiology and costs of SCI and the rehabilitation needs after SCI; however,
      data about the preventability of SCI are lacking. OBJECTIVE: To test the
      hypotheses that most SCIs are preventable and that much of the cost of SCI is
      borne by the public. DESIGN: Retrospective review of medical records and trauma
      registry data. SETTING: A 417-bed county hospital with a level I trauma center.
      METHODS: To evaluate the preventability of SCI, the records of trauma patients
      sustaining SCI from July 1, 1990, through June 30, 1995, were reviewed. The
      criteria for preventability of blunt injuries included the following: failure to
      use restraint devices; intoxication of drivers, motorcyclists, or pedestrians;
      and falls or diving accidents involving the use of drugs or alcohol. The criteria
      for preventability of penetrating injuries included the following: illegal
      possession of a firearm, accidental discharge of a weapon, and suicide attempts.
      Statistics were performed with the paired Student t test and chi 2 with
      significance attributed to a P value less than .05. RESULTS: Spinal cord injury
      occurred in 150 patients; 71% of the injuries were the result of blunt trauma.
      Injury was potentially preventable in 74% of the blunt injuries and 66% of the
      penetrating injuries (P = .15). Patients with a penetrating SCI were younger (P <
      .001) and relied more on public funding than did those with a blunt SCI (65% vs
      81%; P = .05). CONCLUSIONS: Most SCIs are preventable with strict enforcement of
      existing statutes. Furthermore, the financial burden of these preventable
      injuries is largely borne by the public.

PMID- 9230866
TI  - Molecular genetic analysis of a patient with hereditary nonpolyposis colorectal
      cancer syndrome.
AB  - Hereditary nonpolyposis colorectal cancer types I and II constitute approximately
      5% to 10% of the cases of colorectal cancer annually. Recognition of its clinical
      features and identification of affected families are imperative for appropriate
      medical and surgical management. Furthermore, molecular analysis can be performed
      in such families because the DNA mismatch repair genes have been identified as
      being mutated, thereby leading to microsatellite instability. We describe a 33
      year-old woman with ovarian, uterine, and colorectal cancer, whose family, on
      close examination, had features consistent with hereditary nonpolyposis
      colorectal cancer. The patient had evidence of microsatellite instability in her
      colon cancer.

PMID- 9230867
TI  - Simple technique for pancreatogastrostomy and the histological findings of
      pancreatogastric anastomosis.
AB  - The leakage of pancreatic juice is the most serious complication after
      pancreatoduodenectomy. In an attempt to lessen the incidence of this
      complication, we have developed a simple technique for the anastomosis of
      pancreatogastrostomy. Since March 14, 1995, we have already performed surgical
      procedures on 8 cases of pancreatogastrostomy using this technique and as yet
      have never experienced fatal complications. We report the autopsy findings of
      pancreatogastric anastomosis histologically. The specimen taken from the
      anastomosis reveals good mucosal continuity. This result suggests the importance
      of reliable sutures between the pancreatic parenchyma and the full thickness of
      the gastric wall for the anastomosis of pancreatogastrostomy.

PMID- 9230869
TI  - Vitamin E supplements. Clinical practice is changing with new data on preventive
      care of older patients.

PMID- 9230868
TI  - Cardiopulmonary resuscitation: a promise as yet largely unfulfilled.
AB  - After failure of initial external defibrillation, restoration of spontaneous
      circulation is largely contingent on rapid and effective reversal of myocardial
      ischemia by both mechanical and pharmacologic means. Despite the introduction of
      modern cardiopulmonary resuscitation (CPR) more than 35 years ago, its universal
      acceptance, and its wide implementation, no improvements in outcome excepting
      early defibrillation have been documented over these many years. The science of
      CPR therefore is still in its infancy. It was incorrectly assumed that all that
      needs to be known is known and that the need for scientific research was
      therefore not apparent. Accordingly, serious resuscitation research was neither
      encouraged nor equitably supported. The ABCs of CPR currently provide for the
      establishment of a patent airway (A) and intermittent positive pressure
      ventilation, preferably with oxygen-enriched air (B). These are to be immediately
      followed with precordial compression (C). This ordering of priorities, however,
      is based on consensus rather than objective outcome measurements. The ABCs
      recently have been seriously challenged on the basis of results of both
      experimental and clinical studies. Conventional external precordial compression
      restores systemic blood flow. It may be used by both professional and
      nonprofessional CPR providers, especially bystanders, because of its apparent
      simplicity and noninvasiveness. However, manual or mechanical external precordial
      compression typically generates cardiac outputs that represent less than 30% of
      normal values. Coronary blood flow, which is critical for restoration of
      spontaneous circulation, is correspondingly reduced. Accordingly, several
      alternatives to conventional precordial compression have been proposed with the
      intent of increasing cardiac output and both coronary and cerebral blood flows.
      Among the large number of pharmaceutical agents initially recommended for cardiac
      resuscitation, only agents that produce peripheral vasoconstriction are of proved
      benefit. Epinephrine has been the preferred vasopressor agent for the management
      of cardiac arrest for more than 35 years because of its alpha-adrenergic effects.
      However, the potentially adverse effects of epinephrine are related to its beta
      adrenergic inotropic actions. The beta-adrenergic actions account for
      disproportionate increases in myocardial oxygen consumption with increased
      severity of myocardial ischemic injury and provocation of ectopic ventricular
      tachycardia and ventricular fibrillation. Nevertheless, epinephrine remains the
      drug of choice, although adrenergic drugs with selective alpha-adrenergic actions
      or nonadrenergic vasoconstrictor drugs are likely to emerge as useful
      alternatives. Experimental and clinical observations have led to identification
      of continuous monitoring of both end-tidal carbon dioxide and ventricular
      fibrillation waveforms as practical noninvasive guides because they are highly
      correlated with both cardiac output and coronary blood flow. Both end-tidal
      carbon dioxide and ventricular fibrillation waveforms now serve as predictors of
      the likelihood of successful resuscitation. These two measurements may now be
      used to guide interventions and especially to assure optimal precordial
      compression. It is well established that sudden death among adults is
      predominantly due to malignant ventricular arrhythmias and ventricular
      fibrillation. Early defibrillation serves as an unequivocally effective immediate
      intervention. Minimally trained first responders and members of the general
      public are being enfranchised to use automated external defibrillators for very
      early defibrillation. Use of these devices by bystanders is the most promising
      new intervention since CPR was first proposed in the early 1960s.
      Postresuscitation ventricular dysrhythmias and heart failure are now called
      postresuscitation myocardial dysfunction. This complication has been recognized
      as a leading cause of the high postresuscitation mor

PMID- 9230870
TI  - Geriatrics photo quiz. Pulmonary embolism.

PMID- 9230871
TI  - Pruritic eruption of the eyes. Red, scaly, and crusted plaques appear following
      weekly manicure.

PMID- 9230872
TI  - Antibiotic resistance: why is it increasing in nursing homes?
AB  - Causes of the apparent increase in antibiotic resistance in the bacterial flora
      of nursing homes are multifactorial. Today's nursing home patients are older, in
      poorer health, and less able to function independently than has been true in the
      past. Infection and antibiotic use in this population may increase selective
      pressure for the emergence of resistant strains. The efficient transfer to
      nursing homes of patients from acute-care settings also contributes to the
      increase in colonization or infection with highly resistant bacteria. Prudent
      restraint in the use of antibiotics and better infection control in nursing homes
      may reduce or retard the increase or spread in resistant infections.

PMID- 9230873
TI  - Fecal incontinence: three steps to successful management.
AB  - Fecal incontinence is a socially disruptive problem that occurs with increased
      frequency in older individuals. The causes of incontinence in this age group
      include abnormalities of rectal storage capacity, fecal impaction with overflow
      incontinence and disorders of rectosphincteric continence mechanisms. Evaluation
      consists of a careful history and physical examination, followed by studies of
      anorectal structure and function in selected patients. Therapeutic approaches
      include disimpaction and colonic cleansing, dietary modifications, pharmacologic
      agents, biofeedback techniques, and surgery. Most patients can be treated
      successfully with nonsurgical measures, with improvement in their quality of
      life.

PMID- 9230874
TI  - Midlife crisis: helping patients cope with stress, anxiety, and depression.
AB  - Midlife may be associated with changes and losses, including declining health
      status, retirement, caregiving for aging parents, and unexpected responsibility
      for adult children or grandchildren. Suicide rates increase with age. Depression
      and substance abuse are common but often under-recognized and undertreated. The
      primary care physician can promote healthy aging by appropriately diagnosing and
      treating midlife depression and substance abuse, making appropriate referrals for
      psychotherapy, and utilizing the support and educational resources of community
      and national organizations.

PMID- 9230875
TI  - Acute abdominal pain: a medical emergency in older patients.

PMID- 9230876
TI  - Promise and problems of Bcl-2 antisense therapy.

PMID- 9230877
TI  - Ductal carcinoma in situ of the breast: a new model.

PMID- 9230878
TI  - Are changes in end-of-life cancer care coming? IOM, ASCO tackle issues.

PMID- 9230879
TI  - Virtual reality researchers seek to minimize invasive diagnostic procedures.

PMID- 9230880
TI  - Keying educational messages to high-risk populations.

PMID- 9230881
TI  - A science for the art of consensus.

PMID- 9230882
TI  - Tocopherols and the etiology of colon cancer.
AB  - Colorectal cancer is the second most common cause of cancer deaths in the United
      States for both sexes. Considerable evidence suggests that the risk of this
      cancer is increased by the mutagenic actions of free radicals, which are produced
      during oxidation reactions. Dietary factors, the intestinal flora (bacteria), and
      endogenously produced metabolites contribute to the production of free radicals
      in the colon. Dietary antioxidants, such as vitamin E, should reduce the levels
      of these harmful oxidation products. In the absence of vitamin E, polyunsaturated
      fats can be oxidized in the colon to produce mutagens, such as lipid
      hydroperoxides and malondialdehyde. Furthermore, fecal bacteria can generate a
      high flux of reactive oxygen species (e.g., the superoxide radical [O2*-]) at the
      surface of the intestinal lumen, and inflammatory cells in close proximity to the
      colon can produce reactive nitrogen species (e.g., nitrogen dioxide [NO2]).
      Increasing evidence suggests that the different chemical (e.g., alpha- and gamma
      tocopherol) and stereochemical (e.g., RRR- and all-racemic-alpha-tocopherol)
      forms of vitamin E have distinct biologic potencies, pharmacokinetics, and
      different abilities to prevent neoplastic transformation. This review considers
      and evaluates recent studies relating vitamin E and oxidative stress to colon
      cancer, emphasizing the distinct roles of alpha- and gamma-tocopherols. In
      addition, recent findings on the antioxidant/pro-oxidant status of the digesta
      (ingested food) are discussed with respect to the use of antioxidants in chemo
      prevention trials for colon cancer.

PMID- 9230883
TI  - National Institutes of Health Consensus Development Conference Statement: Breast
      Cancer Screening for Women Ages 40-49, January 21-23, 1997. National Institutes
      of Health Consensus Development Panel.
AB  - OBJECTIVE: To provide health care providers, patients, and the general public
      with a responsible assessment of currently available data regarding the
      effectiveness of mammography screening for women ages 40-49. PARTICIPANTS: A non
      Federal, nonadvocate, 12-member panel representing the fields of oncology,
      radiology, obstetrics and gynecology, geriatrics, public health, and epidemiology
      and including patient representatives. In addition, 32 experts in oncology,
      surgical oncology, radiology, public health, and epidemiology, presented data to
      the panel and to a conference audience of 1,100. EVIDENCE: The literature was
      searched through Medline and an extensive bibliography of references was provided
      to the panel and the conference audience. Experts prepared abstracts with
      relevant citations from the literature. Scientific evidence was given precedence
      over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering
      predefined questions, developed its conclusions based on the scientific evidence
      presented in open forum and the scientific literature. The panel composed a draft
      statement that was read in its entirety and circulated to the experts and the
      audience for comment. Thereafter, the panel resolved conflicting recommendations
      and released a revised draft statement at the end of the conference. The final
      statement with a minority report was completed within several weeks after the
      conference. CONCLUSIONS: The Panel concludes that the data currently available do
      not warrant a universal recommendation for mammography for all women in their
      forties. Each woman should decide for herself whether to undergo mammography. Her
      decision may be based not only on an objective analysis of the scientific
      evidence and consideration of her individual medical history, but also on how she
      perceives and weighs each potential risk and benefit, the values she places on
      each, and how she deals with uncertainty. However, it is not sufficient just to
      advise a woman to make her own decision about mammograms. Given both the
      importance and the complexity of the issues involved in assessing the evidence, a
      woman should have access to the best possible relevant information regarding both
      benefits and risks, presented in an understandable and usable form. Information
      should be developed for women in their forties regarding potential benefits and
      risks to be provided to enable each woman to make the most appropriate decision.
      In addition, educational material to accompany this information should be
      prepared that will lead women step by step through the process of using such
      information in the best possible way for reaching a decision. For women in their
      forties who choose to have mammography performed, the costs of the mammograms
      should be reimbursed by third-party payors or covered by health maintenance
      organizations so that financial impediments will not influence a woman's
      decision. Additionally, a woman's health care provider must be equipped with
      sufficient information to facilitate her decisionmaking process. Therefore,
      educational material for physicians should be developed to assist them in
      providing the guidance and support needed by the women in their care who are
      making difficult decisions regarding mammography. The two panel members writing a
      minority report believed the risks of mammography to be overemphasized by the
      majority and concluded that the data did support a recommendation for mammography
      screening for all women in this age group and that the survival benefit and
      diagnosis at an earlier stage outweigh the potential risks.

PMID- 9230884
TI  - Induction of apoptosis in small-cell lung cancer cells by an antisense
      oligodeoxynucleotide targeting the Bcl-2 coding sequence.
AB  - BACKGROUND: The emergence of resistance to chemotherapy remains a major problem
      in the treatment of patients with small-cell lung cancer. Elevated expression of
      Bcl-2, a protein that inhibits programmed cell death or apoptosis, has been
      associated with radiation and drug resistance and has been observed in the
      majority of small-cell lung cancer specimens and cell lines. PURPOSE: To test the
      hypothesis that Bcl-2 expression levels are critical for inhibiting apoptosis in
      small-cell lung cancer cells, we used an antisense strategy to reduce Bcl-2
      expression in these cells in an attempt to restore the natural occurrence of
      apoptosis. METHODS: Thirteen antisense oligodeoxynucleotides (ODNs) targeting
      various regions of the bcl-2 messenger RNA and a control scrambled-sequence ODN
      were tested to identify the most effective sequence(s) for reducing Bcl-2 protein
      levels. Northern and western blot analyses were used to examine basal bcl-2
      messenger RNA and protein levels, respectively, in four human small-cell lung
      cancer cell lines (SW2, NCI-H69, NCI-H82, and NCI-N417). SW2 cells were treated
      with the antisense ODNs in the presence of cationic lipids (to facilitate
      uptake), and cytotoxic effects were measured by use of a cell viability assay.
      Flow cytometric analysis of DNA fragmentation and cell morphology was also
      performed. The cytotoxic effect of the most potent antisense ODN was also tested
      on the three other cell lines. RESULTS: The viability of SW2 cells was
      effectively reduced by ODNs that targeted the translation initiation and
      termination sites of the bcl-2 messenger RNA, but ODN 2009 that targeted the
      coding region was the most cytotoxic. Treatment of SW2 cells with 0.15 microM ODN
      2009 for 96 hours reduced their viability by 91% (95% confidence interval [CI] =
      88%-94%) and caused a dose-dependent reduction in Bcl-2 levels that became
      detectable 24 hours after treatment and persisted up to 96 hours; analysis of
      cellular morphology demonstrated that viability was reduced through apoptosis.
      Moreover, ODN 2009 at 0.15 microM was cytotoxic to NCI-H69, NCI-H82, and NCI-N417
      cells, resulting in decreases in cell viability of 82% (95% CI = 78%-86%), 100%,
      and 100%, respectively, after 96 hours of treatment. The cytotoxic effects were
      inversely correlated with the basal Bcl-2 levels in the cell lines (r = -9964). A
      control scrambled-sequence oligodeoxynucleotide had no statistically significant
      effect on the cell lines (P values ranging from .38 to .89). CONCLUSION: We have
      identified a novel antisense ODN sequence (ODN 2009) that effectively reduces the
      viability of small-cell lung cancer cells by reducing Bcl-2 levels and
      facilitating apoptosis.

PMID- 9230885
TI  - Characterization of p53 and p21 functional interactions in glioma cells en route
      to apoptosis.
AB  - BACKGROUND: Alterations of the p53 (also called TP53) gene are one of the most
      common abnormalities in gliomas. We have previously reported that restoration of
      wild-type p53 protein function in glioma cells results in programmed cell death
      (apoptosis). Since p53 functions are mediated by genes that directly control the
      tumor suppressor effect of the p53 protein, understanding the relationship
      between p53 and p53-related genes in glioma cells will aid in the design of more
      rational treatment strategies for brain tumors. PURPOSE: We conducted this study
      to examine the timing of the p53-mediated events preceding apoptosis. More
      specifically, we undertook this work to characterize the genetic and cell cycle
      related factors that may increase the resistance of glioma cells to p53-induced
      apoptosis. METHODS: Two human glioma cell lines (U-251 MG and U-373 MG) that
      express mutant p53 protein and two (U-87 MG and EFC-2) that express wild-type p53
      protein were used. Replication-deficient adenovirus was utilized as an expression
      vector to transfer exogenous p53 and p21 complementary DNAs into the glioma
      cells; control cells were infected with the viral expression vector alone. To
      monitor gene transfer and the expression of exogenous genes (as well as the
      expression of endogenous genes), we used western blot analyses and
      immunohistochemistry analyses. Flow cytometry studies of cellular DNA content
      were performed to determine the cell cycle phenotype of the glioma cells before
      and after treatment. RESULTS: p53-mediated apoptosis was preceded by elevation in
      the levels of the p21 (cell cycle-related) and Bax (apoptosis-related) proteins.
      In addition, cell cycle analyses showed that glioma cells were arrested in the G2
      phase before undergoing cell death. Transfer of p21 induced a G2 block but did
      not induce apoptosis. Moreover, coexpression of p21 and p53 prevented glioma
      cells from undergoing apoptosis. Expression of exogenous p53 in wild-type p53
      cells did not induce elevation of Bax levels, arrest in G2 phase, or apoptosis.
      CONCLUSIONS AND IMPLICATIONS: Our data confirmed the ability of wild-type p53 to
      induce apoptosis in p53 mutant glioma cells. In addition, our results document
      that p21 plays a role in protecting cells from p53-mediated programmed cell death
      and suggest that p53-mediated apoptosis and p21 induction may represent, at least
      in certain cases, opposite signals. Finally, our data suggest that over
      expression of p21 in gliomas may be related to resistance to treatments that
      induce apoptosis.

PMID- 9230886
TI  - Association of tumor angiogenesis with bone marrow micrometastases in breast
      cancer patients.
AB  - BACKGROUND AND PURPOSE: The microscopic detection of tumor cells
      (micrometastases) in bone marrow and the extent of blood vessel formation
      (angiogenesis) in primary tumor specimens are recognized as independent
      prognostic markers in patients with breast cancer. Since micrometastases occur as
      a consequence of interaction between the neoplastic cells and the tumor
      neovasculature, we have examined the relationship between these markers to
      determine whether the degree of angiogenesis is related to the presence of
      micrometastases. METHODS: Micrometastases were identified in bone marrow
      aspirates collected from multiple sites in 214 breast cancer patients prior to
      surgery (mastectomy or lumpectomy). Tumor cells were detected through an
      examination of epithelial membrane antigen expression and an analysis of cell
      morphology. Tumor vascularity was graded semiquantitatively or quantitatively
      (Chalkley point count) after immunohistochemical staining of the CD31 antigen
      expressed by the endothelial cells. The reproducibility and accuracy of the
      vascular grading were validated by use of kappa statistics. Associations between
      micrometastases and clinicopathologic characteristics, including angiogenesis,
      were examined using chi-squared and logistic regression techniques. All tests of
      statistical significance were two-sided. RESULTS: Of the 214 patients, 42 (20%)
      were positive for bone marrow micrometastases and 75 (35%) had tumors of high
      vascular grade. There was 86% agreement between vascular grades assessed twice
      for 35 tumors (kappa statistic = 0.66); for 22 evaluated tumors, there was
      absolute concordance between vascular grade and Chalkley point count. There were
      significant positive associations between tumor angiogenesis and micrometastasis
      (P = .01), tumor grade (P = .003), and estrogen receptor expression (P = .007);
      however, no significant associations were observed with tumor size (P = .9),
      lymph node status (P = .33), vascular invasion (peritumoral blood or lymph
      vessels) (P = .9), menopausal status (P = .17), or age (P = .12). Adjusting for
      confounding factors, multivariate analysis showed that only tumor angiogenesis
      (odds ratio = 2.7; P = .016) and vascular invasion (odds ratio = 2.7; P = .012)
      were significant determinants for the presence of micrometastases. CONCLUSIONS:
      This study suggests that an assessment of tumor angiogenesis and vascular
      invasion gives a reliable indication of the likelihood of the presence of bone
      marrow micrometastases in patients with breast cancer and that both processes
      contribute to metastases.

PMID- 9230887
TI  - Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12
      (IL-12) or other cytokines compared with exogenous IL-12.
AB  - BACKGROUND: Numerous animal model studies have examined the ability of
      genetically engineered tumor cells to release cytokines and to elicit an immune
      memory against the parental tumor. Often only a single cytokine is studied, and
      few comparative studies have been conducted. PURPOSE: We evaluated the antitumor
      efficacy of adenocarcinoma cells engineered to release interleukin (IL)-12 in a
      mouse model system. The efficacy of this cytokine was compared with that of other
      cytokines released by engineered adenocarcinoma cells and that of exogenous IL-12
      administered both locally and intraperitoneally. METHODS: BALB/cAnCr mice were
      inoculated with syngeneic parental mammary adenocarcinoma (TSA) cells in
      quantities sufficient to lead to tumors in all inoculated mice. TSA cells
      engineered to release IL-12 (TSA-IL12) were also injected into normal and
      selectively immunosuppressed BALB/cAnCr mice. Tumor incidence, growth, and
      rejection patterns were evaluated by the measurement of neoplastic masses and by
      the study of the histologic and ultrastructural features of the tumor site. The
      effects of local or intraperitoneal administration of recombinant IL-12 (rIL-12)
      on tumor-bearing animals were also studied. RESULTS: Most mice rejected TSA-IL12
      cells through a CD8-positive, T-lymphocyte-dependent reaction associated with
      macrophage infiltration, vessel damage, and necrosis. The systemic immunity of
      mice that had rejected TSA-IL12 cells to a subsequent challenge with parental TSA
      cells was less efficient than that elicited by TSA cells engineered to release IL
      4 or IL-10 but equivalent to that elicited by TSA cells engineered to release IL
      2, IL-7, and interferon alfa. Compared with TSA cells engineered to produce other
      cytokines, TSA-IL12 cells were the most efficient in curing mice with established
      TSA tumors; injection of 0.1 million proliferating cells contralaterally to the
      tumor growth area cured five of 15 mice bearing 1-day-old tumors; injection of
      the same dose of proliferating cells into the tumor growth area cured two of 20
      tumor-bearing mice. However, two 5-day courses with a nontoxic dose (0.1
      microgram) of rIL-12 given intraperitoneally cured a similar proportion of these
      animals (six of 20). Only two of 20 mice with 7-day-old TSA tumors were cured by
      vaccination with proliferating TSA-IL12 cells, whereas 24 of 30 mice with such
      tumors were cured by intraperitoneal administration of rIL-12. CONCLUSIONS: TSA
      cells engineered to release IL-12 are rejected by most mice; the ensuing immune
      memory for TSA parental cells, however, was less efficient than that elicited by
      proliferating TSA cells engineered to release other cytokines (e.g., IL-4, IL-10,
      and possibly interferon gamma). The immune reaction elicited by TSA-IL12 cells
      was the most efficient in curing mice with established TSA tumors; notably
      though, the same or a better cure rate was obtained with rIL-12 given
      intraperitoneally.

PMID- 9230888
TI  - Assessment of hormone dependence of comedo ductal carcinoma in situ of the
      breast.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) represents 20%-30% of breast cancers
      detected by clinical screening (i.e., mammography). More than 50% of DCIS lesions
      may be estrogen receptor negative and, therefore, hormone independent. However,
      the role of estrogen in the natural history of DCIS is unknown. PURPOSE: A novel
      in vivo (i.e., xenograft) model was developed to determine to what degree DCIS
      lesions depend on estrogen for growth. METHODS: Specimens of breast tissue were
      collected from 52 women during diagnostic or therapeutic surgical procedures.
      Portions of each specimen were randomly selected and analyzed by histology and
      thymidine labeling (to measure cell proliferation). The remainder of each
      specimen was implanted into five to 18 athymic BALB/c nu/nu mice (depending on
      the amount of tissue available), with eight pieces of approximately 2 mm x 2 mm x
      1 mm implanted at different locations on the back of each mouse. Half of the mice
      received implants containing estrogen (2 mg 17 beta-estradiol), and the other
      half received placebo implants. Levels of cell proliferation in xenografts,
      recovered after 14, 28, 42, or 56 days in the mice, were measured by thymidine
      labeling or by immunohistochemistry through use of an antibody specific for the
      Ki-67 nuclear antigen. Immunohistochemistry was also used to measure the levels
      of estrogen receptor in the tissue specimens. Serum 17 beta-estradiol levels in
      the mice were measured by radioimmunoassay. RESULTS: Initial levels of cell
      proliferation were approximately 10-fold higher in 10 specimens with estrogen
      receptor-negative, comedo (i.e., more malignant in appearance) DCIS than in four
      specimens with estrogen receptor-positive DCIS (mean proliferation indices: 22%
      versus 1.9%, respectively; two-sided P < .001). Xenografts from the majority of
      specimens survived up to 56 days in the mice and maintained good architectural
      and cellular preservation. Estrogen treatment of the xenograft-bearing mice had
      no effect on the high level of cell proliferation observed in estrogen receptor
      negative, comedo DCIS specimens (two-sided P = .89). In contrast, increased
      levels of cell proliferation in response to estrogen supplementation were
      measured in three estrogen receptor-positive, noncomedo DCIS specimens (two-sided
      P < .001). However, even with estrogen treatment, cell proliferation levels in
      estrogen receptor-positive DCIS specimens did not reach those seen in estrogen
      receptor-negative DCIS specimens. CONCLUSION AND IMPLICATION: Estrogen receptor
      negative, comedo DCIS lesions appear to be estrogen independent; therefore,
      antiestrogen (e.g., tamoxifen) therapy may not benefit patients with comedo DCIS.

PMID- 9230889
TI  - Benzene and the dose-related incidence of hematologic neoplasms in China. Chinese
      Academy of Preventive Medicine--National Cancer Institute Benzene Study Group.
AB  - BACKGROUND: Benzene is a widely distributed environmental contaminant known to
      cause leukemia, particularly acute nonlymphocytic leukemia, and perhaps other
      hematologic neoplasms and disorders. Few epidemiologic studies, however, have
      been able to address relationships between the extent of benzene exposure and the
      level of risk. PURPOSE: A large cohort study was carried out in China to evaluate
      the risks of developing specific hematologic neoplasms and selected related
      disorders in relationship to quantitative estimates of occupational benzene
      exposure. METHODS: A cohort of 74828 benzene-exposed and 35805 unexposed workers
      employed from 1972 through 1987 in 12 cities in China was identified and followed
      to determine the incidence of hematologic neoplasms and related disorders.
      Estimates of benzene exposure were derived from work histories and available
      historic benzene measurements. Existing pathologic material and supporting
      medical records were reviewed to establish diagnoses of disease. Relative risks
      (RRs) (i.e., ratios of incidence rates for specific hematologic neoplasms and
      related disorders in the benzene-exposed group to incidence rates in the
      unexposed group) were determined by use of Poisson regression analysis, with
      stratification by age and sex. RESULTS: For workers historically exposed to
      benzene at average levels of less than 10 parts per million (ppm), the RR for all
      hematologic neoplasm combined was 2.2 (95% confidence interval [CI] = 1.1-4.2),
      and, for the combination of acute nonlymphocytic leukemia and related
      myelodysplastic syndromes, the RR was 3.2 (95% CI = 1.0-10.1). For individuals
      who were occupationally exposed to benzene at constant levels of 25 ppm or more,
      the RR for the combination of acute nonlymphocytic leukemia and related
      myelodysplastic syndromes was 7.1 (95% CI = 2.1-23.7). Workers with 10 or more
      years of benzene exposure had an RR of developing non-Hodgkin's lymphoma of 4.2
      (95% CI = 1.1-15.9), and the development of this neoplasm was linked most
      strongly to exposure that had occurred at least 10 years before diagnosis (i.e.,
      distant exposure) (P for trend = .005, two-sided). In contrast, the risk for the
      combination of acute nonlymphocytic leukemia and related myelodysplastic
      syndromes was significantly increased among those with more recent benzene
      exposure (P for trend = .003, two-sided), but it was not linked to distant
      exposure (P for trend = .51, two-sided). CONCLUSIONS: The results of this study
      suggest that benzene exposure is associated with a spectrum of hematologic
      neoplasms and related disorders in humans. Risks for these conditions are
      elevated at average benzene-exposure levels of less than 10 ppm and show a
      tendency, although not a strong one, to rise with increasing levels of exposure.
      The temporal pattern of benzene exposure appears to be important in determining
      the risk of developing specific diseases.

PMID- 9230890
TI  - Aspartame consumption in relation to childhood brain tumor risk: results from a
      case-control study.

PMID- 9230891
TI  - Clinical application of ultrasensitive prostate-specific antigen assays.

PMID- 9230892
TI  - Re: Neuroblastoma screening test may do more harm than good.

PMID- 9230893
TI  - Mapping QTLs for submergence tolerance in rice by AFLP analysis and selective
      genotyping.
AB  - By combining the amplified fragment length polymorphism (AFLP) technique with
      selective genotyping, we constructed a linkage map for rice and assigned each
      linkage group to a corresponding chromosome. The AFLP map, consisting of 202 AFLP
      markers, was generated from 74 recombinant inbred lines (RIL) which were selected
      from both extremes of the population (250 lines) with respect to the response to
      complete submergence. Map length was 1756 cM, with an average interval size of
      8.5 cM. To assign linkage groups to chromosomes, we used 50 previously mapped
      AFLP markers as anchor markers distributed over the 12 chromosomes. Other AFLP
      markers were then assigned to specific chromosomes based on their linkage to
      anchor markers. This AFLP map is equivalent to the RFLP/AFLP map constructed
      previously as the anchors were in the same order in both maps. Furthermore, tests
      with two restriction fragment length polymorphism (RFLP) markers and two sequence
      tagged site (STS) markers showed that they mapped in the expected positions.
      Using this AFLP map, a major gene for submergence tolerance was localized on
      chromosome 9. Quantitative trait loci (QTL) associated with submergence tolerance
      were detected on chromosomes 6, 7, 11, and 12. We conclude that the combination
      of AFLP mapping and selective genotyping provides a much faster and easier
      approach to QTL identification than the use of RFLP markers.

PMID- 9230894
TI  - Comparative analysis in three fungi reveals structurally and functionally
      conserved regions in the Mig1 repressor.
AB  - The Mig1 repressor is a key effector in glucose repression in the yeast
      Saccharomyces cerevisiae. To gain further insights into structure-function
      relationships, we have now cloned the MIG1 homologue from the yeast Kluyveromyces
      marxianus. The amino acid sequence deduced from KmMIG1 differs significantly from
      ScMig1p outside the highly conserved zinc fingers. However, 12 discrete conserved
      motifs could be identified in a multiple alignment that also included the K.
      lactis Mig1p sequence. We further found that KmMig1p is fully functional when
      expressed in S. cerevisiae. First, it represses the SUC2 promoter almost as well
      as ScMig1p. This repression requires the Cyc8 and Tup1 proteins and is dependent
      on a C-terminal region comprising several conserved leucine-proline repeats.
      Second, KmMig1p is regulated by glucose in S. cerevisiae, and a KmMig1-VP16
      hybrid activator is inhibited by the ScSnf1p kinase in the absence of glucose.
      This suggests that KmMig1p has retained the ability to interact with several S.
      cerevisiae proteins, and reinforces the notion that the conserved motifs are
      functionally important. Finally, we found that the physiological role of Mig1p
      also is conserved in K. marxianus, since KmMig1p represses INU1, the counterpart
      of SUC2 in this organism.

PMID- 9230895
TI  - Molecular and biochemical characterization of a proteasome subunit from rice and
      carrot cells.
AB  - Proteasomes function mainly in the ATP-dependent degradation of proteins that
      have been conjugated with ubiquitin. We isolated a cDNA clone for a rice protein
      that exhibited high homology to subunit C2 of proteasomes. Southern blot analysis
      revealed that the corresponding gene was present as a single copy in the rice
      genome. After fractionation of a crude extract from cultured cells, a 35-kDa
      protein that cross-reacted with antibodies against the C2 subunit was recovered
      in the peak fraction of both 20 S and 26 S complexes. The same antibodies cross
      reacted with two proteins in seedlings, one of which was the same as that
      detected in cultured cells. The level of the protein was reduced in roots under
      conditions of high salinity. The 35-kDa protein was not detected in the nuclei of
      rice of carrot cells. However, during somatic embryogenesis of carrot cells, the
      C2 subunit was found in the nucleus at the globular stage, and it gradually
      disappeared in the period from the heart to the torpedo stage. Cells at the
      globular stage are proliferating rapidly, thus, it is possible that proteasomes
      are associated with the proliferation of plant cells.

PMID- 9230896
TI  - Molecular evolution and functional relevance of the chalcone synthase genes of
      pea.
AB  - We have isolated seven genomic chalcone synthase (CHS) genes and six classes of
      CHS cDNA from elicitor-treated pea tissues. Comparison of the nucleotide
      sequences of the coding regions revealed the existence of eight members of the
      CHS gene family in pea. These can essentially be divided into three groups
      (PSCHS1, 2 and 8; PSCHS3, 4 and 5; and PSCHS6 and 7) on the basis of nucleotide
      and or amino acid sequence comparisons of the coding regions, introns and
      promoter regions. We previously reported that the accumulation of CHS mRNAs is
      induced by elicitor treatment. Accumulation of CHS mRNA was observed mainly in
      roots and very little was found in floral organs. To specifically detect
      expression of each CHS gene in various types of pea cells. S1 nuclease protection
      assays were performed. Interestingly, the classification of the eight members of
      the CHS gene family based on the sequence identity was found to reflect their
      expression patterns as determined by the S1 nuclease protection assay. The first
      group of CHS genes, PSCHS1, 2 and 8, was strongly induced not only by elicitor
      treatment and UV irradiation but is also constitutively expressed in root and
      flower tissues. The second group, PSCHS3, 4 and 5, was also strongly induced by
      elicitor treatment and UV irradiation but is constitutively expressed only in
      root. Expression of the third group, PSCHS6 and 7 was barely detectable in any of
      the organs tested and was not influenced by environmental stimuli such as
      elicitor or UV. Furthermore, sequence analysis of the promoter region of each
      member of the CHS gene family revealed that putative cis-regulatory elements,
      such as Box-I. Box-II and G-Box, were conserved only in PSCHS1, 2, 3, 4 and 5.
      From these results we propose that an ancestral CHS gene might have given rise to
      defense response-related (UV irradiation- and elicitor-responsive) and -unrelated
      (unresponsive) genes at an early stage of evolution, followed by divergence
      within these subclasses based upon the developmental program in pea.

PMID- 9230897
TI  - A meiotically reproducible chromosome length polymorphism in the ascomycete
      fungus Ophiostoma ulmi (sensu lato).
AB  - We have followed the transmission of Ophiostoma ulmi s.l. chromosome length
      polymorphisms (CLPs) into the F2 generation to determine the reproducibility of a
      genome rearrangement culminating in the conversion of a 1.0 Mb chromosome into a
      800 kb chromosome. The 1.0 Mb chromosome in strain CESS16K is thus far unique
      among O ulmi s.l. wild-type strains, as no other wild-type strains have been
      observed with chromosomes smaller than 2.3 Mb. It has been previously shown that
      the 1.0 Mb chromosome is mitotically stable, carries at least one normally
      expressed gene, and is transmitted through meiosis. In this study, a series of
      crosses were performed to further elucidate the pattern of inheritance of the 1.0
      Mb chromosome and the process of conversion of the 1.0 Mb species to 800 kb. In
      crosses where the 1.0 Mb chromosome was allowed to pair with itself or with the
      800 kb chromosome, all progeny inherited a copy of the 1.0 Mb or 800 kb form,
      further demonstrating the A-type nature of these small chromosomes. When a cross
      was repeated between the strains CESS16K (1.0 Mb chromosome) and FG245Br-O (no
      1.0 Mb or 800 kb chromosome), the occurrence of a 800 kb chromosome was observed
      in 9% of the progeny. A reciprocal cross between an 800 kb strain and a strain
      with no 800 kb or 1.0 Mb chromosome was conducted, and a progeny strain
      containing a 1.0 Mb chromosome was recovered. The reproducibility and
      reciprocality of the 1.0 Mb to 800 kb chromosome conversion demonstrates that
      meiotic processes are responsible for this CLP, and that O. ulmi s.l. strains
      with various divergent genome architectures can remain sexually compatible.

PMID- 9230898
TI  - Alloplasmic wheats with Aegilops crassa cytoplasm which express photoperiod
      sensitive homeotic transformations of anthers, show alterations in mitochondrial
      DNA structure and transcription.
AB  - Alloplasmic wheat. Triticum aestivum cv. Norin 26, with Aegilops crassa
      cytoplasm, shows photoperiod-sensitive cytoplasmic male sterility (PCMS). This
      alloplasmic line expresses pistillody of anthers only when grown in long-day
      conditions (> 15 h light). To assess the molecular basis of the PCMS, we carried
      out Southern and Northern hybridization analyses on mitochondrial DNAs and RNAs
      isolated from seedlings of alloplasmic lines showing various PCMS phenotypes
      using probes for twelve mitochondrial genes. All RFLP patterns of mitochondrial
      DNA from alloplasmic lines greatly differed from those of common wheat, and were
      slightly changed from those of the parental species, i.e., Ae. crassa. This
      indicates that nuclear substitutions between related plant species induce
      structural alterations in the mitochondrial genome. Furthermore, RFLP patterns of
      (cr)-N61 and FR-mutant probed with coxIII and orf25 were identical with each
      other, but different from those of the other alloplasmic lines, indicating that
      the nuclei of N61 and FR-mutant harbor some gene(s) that induces structural
      alterations of the mitochondrial genome in the coxIII and orf25 regions. The
      transcription patterns of atp6 and cob in Ae. crassa type were different from
      those of T. aestivum type. Furthermore, the orf25 transcript in alloplasmic
      wheats was about 300 nucleotides longer than that of euplasmic lines, including
      the Ae. crassa pure line, suggesting that transcription patterns of orf25 are
      associated with recovery from the PCMS phenomenon. These data clearly show the
      mutual cross-talk between the nuclear genome and chondriome. These observations
      raise the possibility that the dysfunction of mitochondria caused by the failure
      of a cooperative control of mitochondrial gene(s) expression influences the
      pathway of flower morphogenesis, especially in the process that determines organ
      identity.

PMID- 9230899
TI  - Lack of correlation between binding of EcoRII methyltransferase to DNA duplexes
      containing mismatches and the promotion of C to T mutations.
AB  - The cytosine methyltransferases (MTases) M. HhaI and M. HpaII bind substrates in
      which the target cytosine is replaced by uracil or thymine, i.e. DNA containing a
      U:G or a T:G mismatch. We have extended this observation to the EcoRII MTase (M.
      EcoRII) and determined the apparent Kd for binding. Using a genetic assay we have
      also tested the possibility that MTase binding to U:G mismatches may interfere
      with repair of the mismatches and promote C:G to T:A mutations. We have compared
      two mutants of M. EcoRII that are defective for catalysis by the wild-type enzyme
      for their ability to bind DNA containing U:G or T:G mismatches and for their
      ability to promote C to T mutations. We find that although all three proteins are
      able to bind DNAs with mismatches, only the wild-type enzyme promotes C:G to T:A
      mutations in vivo. Therefore, the ability of M. EcoRII to bind U:G mismatched
      duplexes is not sufficient for their mutagenic action in cells.

PMID- 9230900
TI  - Genetic analysis of sterile mutants in the dpy-5 unc-13 (I) genomic region of
      Caenorhabditis elegans.
AB  - Essential genes were identified in the 1.5-map unit dpy-5 unc-13 region of
      chromosome I in the Caenorhabditis elegans genome by rescuing lethal mutations
      using the duplication sDp2. In this paper, we report the mapping and
      complementation testing of lethal mutations, 45 of which identify 18 new,
      essential genes. This analysis brings the number of essential genes defined by
      the sDp2 rescue of lethal mutants to 97; 64 of these map between dpy-5 and unc
      13. 61% of these essential genes are identified by more than one allele.
      Positioning of the mutations was done using the breakpoints of six duplications.
      The mutant phenotypes of 14 loci essential for fertility were characterized by
      Nomarski microscopy and DAPI staining. None of the mutants were rescued by wild
      type male sperm. The cytological data showed that four genes produced mutants
      with defects in gonadogenesis. let-395. let-603, let-605 and let-610. Mutations
      in seven genes, let-355, let-367, let-384, let-513, let-544, let-545 and let-606,
      affected germ cell proliferation or gametogenesis. Mutants for the remaining
      three genes, let-370, let-599 and let-604, produced eggs that failed to develop
      or hatch. thereby acting as maternal effect lethals. We observed a nonrandom
      distribution of arrest phenotypes with regard to map position.

PMID- 9230901
TI  - Alignment of the genetic and physical maps in the dpy-5 bli-4 (I) region of C.
      elegans by the serial cosmid rescue of lethal mutations.
AB  - Lethal mutations in the 0.5 map unit region between dpy-5 and bli-4 on chromosome
      I in Caenorhabditis elegans were serially rescued using cosmid-containing
      transgenic strains. All the lethal mutations analyzed came from a set of 495 EMS
      induced, sDp2-rescued lethals described previously. Germline transformation with
      cosmid DNA was used to create 25 transgenic strains bearing heritable
      extrachromosomal arrays. These arrays were used as small duplications for the
      fine-scale mapping of essential genes, via the rescue of lethal mutations. Lethal
      mutations in 13 essential genes have been phenotypically rescued, allowing the
      alignment of the genetic and physical maps in this region. Extrachromosomal
      arrays were found to be transmitted 2- to 7-fold less frequently in oocytes than
      in hermaphrodite sperm for 12 of the 16 arrays that were examined. Three of these
      strains showed a subsequent 4- to 13-fold increase in array stability in oocytes.
      This phenomenon may be influenced by cosmid sequences. Early mitotic loss of the
      arrays was observed in all 17 transgenic strains examined, suggesting that loss
      of the array can occur at any time during development when cell divisions are
      occurring. As a result of this work, 13 of the essential loci positioned between
      dpy-5 and bli-4 are anchored to the physical map, thereby providing links between
      the physical and genetic maps on average every 85 kb.

PMID- 9230902
TI  - The geranylgeranyl diphosphate synthase gene of Gibberella fujikuroi: isolation
      and expression.
AB  - The rice pathogen, Gibberella fujikuroi, produces large amounts of gibberellins,
      a group of natural plant hormones, which induce the superelongation (bakanae)
      disease of rice. Gibberellins are diterpenoid compounds which are synthesized via
      the isoprenoid pathway. Here we report the isolation and molecular
      characterization of the geranylgeranyl diphosphate synthase (ggs) gene from G.
      fujikuroi. Geranylgeranyl diphosphate synthase is a key enzyme in isoprenoid
      biosynthesis. Southern blot analysis showed that G. fujikuroi has a single copy
      of the ggs gene, which is not linked to the farnesyl diphosphate synthase gene.
      This indicates that the genes of the isoprenoid pathway are not clustered in the
      fungal genome. The ggs gene is not interrupted by an intron and codes for a
      polypetide of 418 amino acids. Peptide sequence comparison showed a high degree
      of similarity to the corresponding Neurospora crassa gene (al-3). However,
      transcription analyses revealed that the ggs gene, in contrast to the analogous
      N. crassa gene, is not regulated by blue light. Ammonium and glucose did not
      affect the transcription of the G. fujikuroi ggs gene, indicating that it is not
      subject to nitrogen and carbon catabolite repression. The G. fujikuroi gene
      complements a N. crassa al-3 mutant.

PMID- 9230903
TI  - Homologous recombination involving cox2 is responsible for a mutation in the cmS
      specific mitochondrial locus of Petunia.
AB  - We have characterized the only mutation detected so far in S-Pcf, the
      mitochondrial cytoplasmic male sterility (CMS)-specific locus of petunia. This
      locus consists of three open reading frames (ORFs): the first contains part of
      atp9, an intron-less cox2 pseudogene (which does not contain the original cox2
      ATG) and the unidentified reading frame urf-s; the second and third ORFs
      correspond to the only copies of nad3 and rps12 genes in the genome,
      respectively. In the cell line R13-138, which was generated from a male-sterile
      somatic hybrid (line SH13-138), a change in the first ORF of the S-Pcf locus has
      been characterized: the atp9 sequence has been lost, while exonl of the normal
      copy of the cox2 gene (including the original ATG sequence) and the adjacent 5'
      sequence of the petunia recombination repeat, have been introduced. The data
      suggest that this reorganization of mtDNA is the consequence of a homologous
      recombination event involving part of the cox2 coding region, and that the cox2
      coding region may serve as an active site for inter- or intra-mtDNA homologous
      recombination. The results further suggest that in line SH13-138 (or during its
      maintenance in tissue culture), segregation of the S-Pcf-containing mtDNA
      molecules has occurred, and the mutant mtDNA is now predominant in the
      population.

PMID- 9230904
TI  - Germ line transposition of the copia retrotransposon in Drosophila melanogaster
      is restricted to males by tissue-specific control of copia RNA levels.
AB  - Germ line transposition rates of the retrotransposon copia were directly measured
      in males and females of an inbred Drosophila melanogaster line, 2b3, which is
      highly polymorphic for copia insertion sites. The elevated germ line
      transposition rate of copia in this line (3-8 x 10(-3) per generation per
      element) is confined to males, with transposition in females being undetectable
      under the conditions of the experiment but at most 50-fold lower than the rate
      for males. To determine the molecular basis of this effect, copia RNA levels were
      measured in whole bodies and germ lines of male and female flies of both the
      unstable 2b3 line and a stable line, Oregon RC-iso, which shows normal rates of
      copia transposition. Both male and female 2b3 flies contain much more copia RNA
      than flies of the stable line. However, 2b3 male germinal tissues contain much
      higher levels of copia RNA than the equivalent female tissues. The highest copia
      expression is detected in maturing primary spermatocytes. Our data show that high
      rates of germ line copia transposition are restricted to males by tissue-specific
      control of RNA levels and suggest that transposition of copia only occurs in fly
      tissues containing more than a relatively high threshold level of copia RNA.

PMID- 9230906
TI  - 1st European Cytogenetics Conference. Athens, Greece, June 22-25, 1997.
      Abstracts.

PMID- 9230905
TI  - Lack of polymorphism within the rRNA operons of group A streptococci.
AB  - Polymerase chain reaction (PCR) ribotyping of many bacterial species has shown
      that polymorphism of the ribosomal RNA (rRNA) operons, within and between
      strains, is common. Restriction fragment length polymorphism (RFLP) analysis of
      the rRNA operons of thirty-two genetically and geographically distinct strains of
      group A streptococci (GAS) revealed that there are only two major HaeIII PCR
      ribotypes. This variation is due to a single nucleotide change within the 16S-23S
      intergenic spacer regions of these operons. As in many other bacterial species,
      this spacer region in streptococci also contains the gene for tRNA(ala). Within
      each GAS isolate, hybridization results are consistent with the presence of six
      rRNA operons. Interestingly, for a given strain, irrespective of its origin, all
      six rRNA operons have the same RFLP pattern. This contrasts with the findings in
      many other bacteria species, where heterogeneity of the rRNA operons within a
      genome is a common feature. This lack of heterogeneity of rRNA operons in an
      organism that is known to acquire genetic sequences through horizontal transfer
      is intriguing.

PMID- 9230907
TI  - International Conference on Chromosome 21 and Medical Research on Down Syndrome.
      Barcelona, Spain, March 14-15, 1997. Abstracts.

PMID- 9230908
TI  - The multiple roles of tumour stroma.
AB  - Since the work of Judah Folkman in the 1970s demonstrating the importance of
      vascularization on tumour growth the many roles played by tumour stroma have been
      demonstrated. Vascular endothelial growth factor/vascular permeability factor
      appears to be the main in vivo inducer of both stromal blood vessels and other
      components of the tumour stroma. Its action is probably mediated through its
      strong and long-lasting effect on microvascular permeability leading to fibrin
      extravasation and organisation ("tumours are wounds that do not heal"). During
      tumour invasion, stromal fibroblasts participate in the degradation of the
      extracellular matrix (ECM) by secreting matrix degrading proteases as well as
      their downstream-activators. Stroma derived factors such as scatter
      factor/hepatocyte growth factor as well as interactions between neoplastic cells
      and the ECM can play a role in both tumour cell migration and proliferation. The
      ECM may also act as a reservoir for growth factors. A novel transcription factor
      encoded by the c-ets 1 proto-oncogene is likely to be involved in the
      transcriptional regulation of both tumour vascularization and invasion. This
      contribution summarizes recent developments in the tumour stroma field.

PMID- 9230909
TI  - Solitary fibrous tumour: clinicopathological, immunohistochemical, and
      ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and
      nasopharynx, urinary bladder and prostate.
AB  - The clinicopathological features of 12 extraserosal solitary fibrous tumours
      (SFT) are described. The age of the patients ranged from 18 to 72 years (mean:
      48.2 years; median: 54 years); 5 were female patients. Seven lesions arose in
      soft tissue (5 in perifascial, and 1 each in subcutaneous and intramuscular
      tissues). They were situated in the groin (2 cases) and the neck, right buttock,
      left scapula, upper arm, and anterior abdominal wall (1 case each). One polypoid
      lesion was seen in in the nasal cavity and 1 in the nasopharynx; 2 neoplasms
      arose in the urinary bladder and 1 was located in the prostate and periprostatic
      tissue. Nine lesions were excised; in 1 patient wide excision was performed and
      in 2 patients, transurethral resection. Limited follow-up of 3 cases revealed a
      benign clinical course. The size of the neoplasms ranged from 1.7 cm to 20.0 cm
      (mean: 5.4 cm; median: 3.5 cm). Histologically, the neoplasms were well
      circumscribed and composed of cytologically bland spindle cells arranged without
      an obvious pattern; focally storiform or fascicular growth patterns were seen.
      Tumour cells were separated by thick bands of collagen demonstrating foci of
      keloid-like hyalinization. Prominent vascularity showing a haemangiopericytoma
      like vascular pattern and vessels with thick, hyalinized vessel walls were seen
      in all cases. Increased mitotic activity was noted in 2 soft tissue cases (4-6
      mitoses in 10 high-power fields); the other cases showed fewer than 2 mitotic
      figures in 10 highpower fields. Immunohistochemically, all cases tested stained
      positively for vimentin, CD34 and CD99, and 2 cases showed focal myofibroblastic
      differentiation. Two cases examined ultrastructurally showed a fibroblastic
      phenotype; focally pinocytic vesicles and microfilaments were identified. SFT
      represents a distinct neoplasm that should be included in the differential
      diagnosis of spindle-cell neoplasms in soft tissue, nasal cavity and nasopharynx,
      urinary bladder, and prostate. Strict diagnostic criteria are necessary to avoid
      overdiagnosis or confusion with more aggressive neoplasms in these locations.

PMID- 9230910
TI  - Polysialylated N-CAM, chromogranin A and B, and secretogranin II in
      neuroendocrine tumours of the lung.
AB  - Highly alpha 2-8-sialylated N-CAM (neural cell adhesion molecule) impairs N-CAM
      mediated cell adhesion. We investigated polysiaN-CAM immunoreactivity in a range
      of neuroendocrine lung tumours: 15 typical carcinoids, 21 atypical carcinoids, 2
      large cell neuroendocrine carcinomas and 12 small cell lung carcinomas were
      selected on a morphological basis and by their immunoreactivity for chromogranin
      A and B and secretogranin II. A progressive loss of chromogranin expression,
      particularly of chromogranin B, was paralleled by the up-regulation of polysiaN
      CAM in histologically more aggressive tumours (P = 0.001). These data support the
      hypothesis that loss of cell-cell adhesion properties might be a relevant factor
      in the origin of the aggressivity of lung neuroendocrine tumours.

PMID- 9230911
TI  - Expression patterns of erbB receptor family in normal urothelium and transitional
      cell carcinoma. An immunohistochemical study.
AB  - The class I tyrosine kinase growth-factor receptors include epidermal growth
      factor receptor (EGFR), ErbB2 (c-erbB-2, HER-2/neu), ErbB3 and ErbB4. To
      elucidate their role in the regulation of homeostasis and carcinogenesis, we
      examined the expression of the receptors in normal urothelium and in urothelial
      carcinoma by immunohistochemistry. EGFR was expressed in the basal cells of
      normal urothelium, while ErbB2, ErbB3 and ErbB4 were present mainly in the
      superficial layer. A distinct reciprocal distribution was observed between the
      EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein
      and Ki-67 antigen (MIB-1) showed a strong positive association with EGFR (P =
      0.002) and an inverse correlation with ErbB2, ErbB3 or ErbB4 (P = 0.0004, 0.0000,
      and 0.001, respectively). With regard to carcinoma, there was no important
      relationship between receptor overexpression and tumour grading (P > 0.1), while
      only EGFR overexpression was correlated with muscular invasion (P = 0.02).
      Coexpression of EGFR-ErbB3 and ErbB3-ErbB4 was more often detected in high-grade
      tumours and correlated with the extent of tumour invasion. Our data indicate that
      class I receptors are differentially expressed in normal urothelium in vivo, but
      an orchestrated expression pattern does not exist during tumorigenesis.

PMID- 9230912
TI  - Effect of spatial arrangement of the basement membrane on cultured pleomorphic
      adenoma cells. Study by immunocytochemistry and electron and confocal microscopy.
AB  - In a cell line from human pleomorphic adenoma (AP2 cells) we studied the response
      of these cells to basement membrane proteins. The culture was characterized as
      myoepithelial-like by transmission electron microscopy and immunocytochemistry.
      AP2 cells were grown in contact with a reconstituted basement membrane
      (Matrigel). Cells grown on Matrigel showed conspicuous phenotypic alterations,
      depending on how the substrate was applied. Cells grown on the top of Matrigel
      developed a dendritic phenotype, exhibiting thin, long and intercommunicating
      cytoplasmic extensions resembling normal myoepithelial cells. Cells grown inside
      Matrigel formed multi-layered clusters. Light, confocal and transmission electron
      microscopy showed that these clusters were formed by double-layered epithelioid
      cells delimiting luminal spaces. The cells facing the lumen were cuboidal,
      showing microvilli at the apical plasmalemmal and junctional complexes. The
      spatial arrangement of basement membrane is a key modulator of morphogenetic
      changes and cytodifferentiation of tumour myoepithelial cell lineage in culture.

PMID- 9230913
TI  - Visceral organ involvement and extracellular matrix changes in beta 2
      microglobulin amyloidosis--a comparative study with systemic AA and AL
      amyloidosis.
AB  - Patterns of amyloid distribution and extracellular matrix changes in the heart
      and gastrointestinal tract were compared among beta 2-microglobulin (B2M), AA
      (secondary), and AL (primary and multiple myeloma-associated) amyloidosis cases.
      B2M amyloid was found to be mainly distributed in the small arterioles, venules,
      endocardium and muscularis propria of these organs, the deposits
      characteristically forming subendothelial nodular lesions in the vessels. A
      marked increase of chondroitin sulfate (CS) was consistently detected in B2M
      amyloid. Heparan sulfate (HS) also showed an increase in amyloid deposits, but
      with less reactivity than CS in the small arterioles or venules. Basement
      membrane structures stained positively for laminin and collagen type IV were
      replaced by negative amyloid deposits. In the AL cases, the muscularis propria of
      the gastrointestinal tract was involved in amyloid deposits, as seen for the B2M
      type, but the vascular amyloid deposits were localized in the media and
      adventitia of larger vessels. Immunoreactivity for HS was more intense than that
      for CS, and no increase in laminin or collagen type IV was observed. In the AA
      cases, amyloid deposits were distributed in the capillaries, small arterioles,
      interstitium of the myocardium and mucosa. Immunoreactivity for laminin and
      collagen type IV was marked, and more intense than that for HS and CS. Although
      the existence of a direct relationship between increase in extracellular matrix
      material and amyloidogenesis remains to be proven, the observed variation in
      extracellular matrix changes in the background of each type of amyloidosis may
      indicate different binding sites of the amyloid precursor proteins, resulting in
      the specific histological features and distribution.

PMID- 9230914
TI  - Diffuse mesangial sclerosis associated with Kawasaki disease: an analysis of
      alpha chains (alpha 1-alpha 6) of human type IV collagen in the renal basement
      membrane.
AB  - A case of diffuse mesangial sclerosis (DMS) associated with Kawasaki disease is
      reported. A previously healthy Japanese girl, aged 4 months, presented with
      clinical features of Kawasaki disease. At week 10 of the illness, she developed
      the nephrotic syndrome, which was refractory to steroid therapy. Renal biopsy
      demonstrated a diffuse mesangial proliferative glomerulonephritis with
      microcystic tubular dilatation and, ultrastructurally, marked thinning of the
      lamina densa in the glomerular basement membrane (GBM) and the tubular basement
      membrane (TBM) of the proximal tubule. She went into chronic renal failure and
      died at the age of 11 months. At autopsy, the kidney revealed DMS.
      Histologically, we found Finnish microcystic disease in its early stages in the
      biopsy. Using a newly developed monoclonal antibody, we analysed the alpha chains
      (alpha 1-alpha 6) of type IV collagen in the GBM and TBM. There was no defective
      constitution of alpha chains on the thin GBM, but the thin TBM of the microcystic
      proximal tubule showed a weak or discontinuous reactivity for alpha 1 and alpha 2
      chains, suggesting faulty formation of the basement membrane. The sclerosing
      glomeruli of the DMS did not depend on collapse of the GBM, which was positive
      for alpha 3-alpha 5 chains, but mainly on the proliferation of mesangial matrix,
      which was positive for alpha 1 and alpha 2 chains.

PMID- 9230915
TI  - A hybrid carcinoma: adenoid cystic carcinoma and salivary duct carcinoma of the
      salivary gland. An immunohistochemical study.
AB  - Hybrid tumours of the salivary glands are very rare entities composed of two
      different tumours, each of which conforms with an exactly defined category. We
      describe an unusual hybrid carcinoma of the palate; it was comprised of an
      adenoid cystic carcinoma and a salivary duct carcinoma with a transitional
      region. These two different compartments showed different characteristics as
      regards cellular differentiation, proliferative activity, and expression of
      oncogene and tumour suppressor oncogene proteins, as revealed by using markers
      for muscle actin, keratin, vimentin, S-100 protein, GFAP, Ki-67, p53, and c-erbB
      2 proteins. This case is the first reported with overexpression of p53 and c-erbB
      2 proteins in the tumour entities. Salivary gland tumours consist of
      heterogeneous histological groups, and each has morphological diversity. This
      case indicates that some of the oncogene and tumour suppressor oncogene proteins
      may help to produce the histological heterogeneity of the salivary gland tumour.

PMID- 9230916
TI  - Ameloblastoma of the mandible metastasizing to the orbit with malignant
      transformation. A histopathological and immunohistochemical study.
AB  - We report here a case of ameloblastoma of the mandible with multiple local
      recurrences and metastasis to the orbit. The patient was a 63-year-old Japanese
      woman with visual disturbance of her right eye. Diagnostic imaging revealed a
      mass occupying the right orbital apex with partial intracranial involvement. She
      had been surgically treated for mandibular ameloblastoma 27 years previously, and
      the tumour had recurred three times in the past 5 years. The orbital tumour and
      recurrent ameloblastomas were investigated histopathologically and
      immunohistochemically. The tumour changed in morphology as it recurred, from
      follicular ameloblastoma without atypia to apparent malignant tumours disclosing
      undifferentiated or squamoid features. On immunohistochemical analysis, staining
      for cytokeratin was positive in the squamoid cells but not in the
      undifferentiated cells. Both histopathologically and immunohistochemically, the
      orbital tumour was almost identical to the undifferentiated recurrent tumour. The
      orbital tumour was distinct from the primary site or sites of recurrence of
      ameloblastoma, and we concluded that the mandibular ameloblastoma underwent
      malignant transformation with multiple recurrences and finally metastasized to
      the orbit.

PMID- 9230917
TI  - What type of chromogranin does PHE5 monoclonal antibody react with?

PMID- 9230918
TI  - Hair follicle involvement in herpes zoster.

PMID- 9230919
TI  - Alternative respiratory pathways of Escherichia coli: energetics and
      transcriptional regulation in response to electron acceptors.
AB  - The electron-transport chains of Escherichia coli are composed of many different
      dehydrogenases and terminal reductases (or oxidases) which are linked by quinones
      (ubiquinone, menaquinone and demethylmenaquinone). Quinol:cytochrome c oxido
      reductase ('bc1 complex') is not present. For various electron acceptors (O2,
      nitrate) and donors (formate, H2, NADH, glycerol-3-P) isoenzymes are present. The
      enzymes show great variability in membrane topology and energy conservation.
      Energy is conserved by conformational proton pumps, or by arrangement of
      substrate sites on opposite sides of the membrane resulting in charge separation.
      Depending on the enzymes and isoenzymes used, the H+/e- ratios are between 0 and
      4 H+/e- for the overall chain. The expression of the terminal reductases is
      regulated by electron acceptors. O2 is the preferred electron acceptor and
      represses the terminal reductases of anaerobic respiration. In anaerobic
      respiration, nitrate represses other terminal reductases, such as fumarate or
      DMSO reductases. Energy conservation is maximal with O2 and lowest with fumarate.
      By this regulation pathways with high ATP or growth yields are favoured. The
      expression of the dehydrogenases is regulated by the electron acceptors, too. In
      aerobic growth, non-coupling dehydrogenases are expressed and used
      preferentially, whereas in fumarate or DMSO respiration coupling dehydrogenases
      are essential. Coupling and non-coupling isoenzymes are expressed
      correspondingly. Thus the rationale for expression of the dehydrogenases is not
      maximal energy yield, but could be maximal flux or growth rates. Nitrate
      regulation is effected by two-component signal transfer systems with membraneous
      nitrate/nitrite sensors (NarX, NarQ) and cytoplasmic response regulators (NarL,
      NarP) which communicate by protein phosphorylation. O2 regulates by a two
      component regulatory system consisting of a membraneous sensor (ArcB) and a
      response regulator (ArcA). ArcA is the major regulator of aerobic metabolism and
      represses the genes of aerobic metabolism under anaerobic conditions. FNR is a
      cytoplasmic O2 responsive regulator with a sensory and a regulatory DNA-binding
      domain. FNR is the regulator of genes required for anaerobic respiration and
      related pathways. The binding sites of NarL, NarP, ArcA and FNR are characterized
      for various promoters. Most of the genes are regulated by more than one of the
      regulators, which can act in any combination and in a positive or negative mode.
      By this the hierarchical expression of the genes in response to the electron
      acceptors is achieved. FNR is located in the cytoplasm and contains a 4Fe4S
      cluster in the sensory domain. The regulatory concentrations of O2 are 1-5 mbar.
      Under these conditions O2 diffuses to the cytoplasm and is able to react directly
      with FNR without involvement of other specific enzymes or protein mediators. By
      oxidation of the FeS cluster, FNR is converted to the inactive state in a
      reversible process. Reductive activation could be achieved by cellular reductants
      in the absence of O2. In addition, O2 may cause destruction and loss of the FeS
      cluster. It is not known whether this process is required for regulation of FNR
      function.

PMID- 9230920
TI  - A competitive inhibition of the mitochondrial NADH-ubiquinone oxidoreductase
      (complex I) by ADP-ribose.
AB  - Considerable quantitative variations in the competitive inhibition of NADH
      oxidase activity of bovine heart submitochondrial particles (SMP) by different
      samples of NAD- were observed. ADP-ribose (ADPR) was identified as the inhibitory
      contaminating substance responsible for variations in the inhibition observed.
      ADPR competitively inhibits NADH oxidation with Ki values (25 degrees C, pH 8.0)
      of 26 microM, 30 microM, and 180 microM for SMP, purified Complex I and three
      subunit NADH dehydrogenase (FP), respectively. ADPR decreases NADH-induced flavin
      reduction and prolongs the cyclic bleaching of FP during aerobic oxidation of
      NADH. Ki for inhibition of the rotenone-sensitive NADH oxidase in SMP by ADPR
      does not depend on delta mu H+. The initial rate of the energy-dependent NAD+
      reduction by succinate is insensitive to ADPR. The inhibitor increases the steady
      state level of NAD+ reduction reached during aerobic succinate-supported reverse
      electron transfer catalyzed by tightly coupled SMP. The results obtained are
      consistent with the proposal on different nucleotide-binding sites operating in
      the direct and reverse reactions catalyzed by the mitochondrial NADH-ubiquinone
      reductase.

PMID- 9230921
TI  - Mutations at tyrosine-235 in the mobile loop region of domain I protein of
      transhydrogenase from Rhodospirillum rubrum strongly inhibit hydride transfer.
AB  - Transhydrogenase from mitochondrial and bacterial membranes couples proton
      translocation to hydride transfer between NAD(H) and NADP(H). The enzyme has
      three domains, of which domains I and III protrude from the membrane. These
      possess the NAD(H)- and NADP(H)-binding sites, respectively, whereas domain II
      spans the membrane. In domain I there is a mobile loop which emanates from the
      surface of the protein, but which closes down upon NAD(H) binding. In this report
      we show that the NADP(H)-dependent reduction of acetylpyridine adenine
      dinucleotide by NADH catalysed by Rhodospirillum rubrum transhydrogenase has
      'ping-pong' kinetics, confirming that the reaction is cyclic. We then describe
      the kinetic and thermodynamic properties of mutants of recombinant domain I
      protein from the R. rubrum enzyme, in which Tyr-235 in the mobile loop has been
      substituted with Phe or Asn residues (dI.Y235F and dI.Y235N, respectively). (1)
      Equilibrium dialysis measurements show that dI.Y235F and dI.Y235N bind NADH more
      weakly than wild-type domain I protein (the Kd increases twofold and fourfold,
      respectively). (2) Reverse transhydrogenation rates (in steady state) of domain I
      depleted membrane vesicles reconstituted with either dI.Y235F or dI.Y235N are
      inhibited by about 50% and 78%, respectively, relative to those obtained in
      reconstitutions with wild-type domain I protein. (3) Reverse transhydrogenation
      rates (in steady state) of mixtures of recombinant domain III protein and either
      dI.Y235F or dI.Y235N are inhibited only by about 10% and 20%, respectively,
      relative to those obtained in mixtures with wild-type protein. (4) Forward
      transhydrogenation rates (in both the complete enzyme and in domain I:III
      complexes) are inhibited even less by the mutations than the reverse reactions.
      (5) In contrast with (1), (2) and (3), cyclic transhydrogenation was strongly
      inhibited in both the reconstituted membrane system and in the recombinant domain
      I:III complexes (only 7-8% activity remains with dI.Y235F, and only 2-3% with
      dI.Y235N). It was recently established that, in contrast to forward and reverse
      transhydrogenation, the cyclic reaction is substantially limited by the rate of
      hydride transfer. It is therefore concluded that mutations at Tyr-235 in the
      mobile loop severely disrupt the hydride transfer step in the catalytic reaction
      of transhydrogenase.

PMID- 9230922
TI  - Characterization of the alpha and beta-subunits of the F0F1-ATPase from the alga
      Polytomella spp., a colorless relative of Chlamydomonas reinhardtii.
AB  - The isolation and partial characterization of the oligomycin-sensitive F0F1-ATP
      synthase/ATPase from the colorless alga Polytomella spp. is described.
      Purification was performed by solubilization with dodecyl-beta-D-maltoside
      followed by Sepharose Hexyl ammonium chromatography, a matrix that interacts with
      the F1 sector of mitochondrial ATPases. The alpha-subunit, which migrates on SDS
      polyacrylamide gels with an apparent molecular mass of 55 kDa, was identified by
      the N-terminal sequencing of 47 residues. This subunit exhibited a short
      extension at its N-terminus highly similar to the one described for the
      unicellular alga Chlamydomonas reinhardtii (Nurani, G. and Franzen L.-G. (1996)
      Plant Mol. Biol. 31, 1105-1116). In whole mitochondria, the alpha-subunit was
      susceptible to limited proteolytic digestion induced by heat. An endogenous
      protease removed the first 22 residues of the mature alpha-subunit. Subunit beta
      was also identified by N-terminal sequencing of 31 residues. This subunit of 63
      kDa exhibited a higher apparent molecular mass than alpha, as judged by its
      mobility on denaturing polyacrylamide gel electrophoresis. This beta-subunit is 7
      8 kDa larger than the beta-subunits of other mitochondrial ATPases. It is
      suggested that the beta-subunit from Polytomella spp. may have a C-terminal
      extension similar to that described for the green alga C. reinhardtii (Franzen,
      L.-G. and Falk, G.(1992) Plant Mol. Biol. 19, 771-780). In addition, it was found
      that the C-terminal extension of the beta-subunit of C. reinhardtii showed
      homology with the endogenous ATPase inhibitors from various sources and with the
      epsilon-subunit from the F0F1-ATP synthase from Escherichia coli, which is
      considered to be a functional homolog of the inhibitor proteins. The data
      reported here provide the first biochemical evidence for a close relationship
      between the colorless alga Polytomella spp. and its photosynthetic counterpart C.
      reinhardtii. It is also suggested that the C-terminal extensions of the beta
      subunits of the ATP synthases from these algae, may play a regulatory role in
      these enzymes.

PMID- 9230923
TI  - On the relationship between matrix free Mg2+ concentration and total Mg2+ in
      heart mitochondria.
AB  - The matrix free magnesium ion concentration, [Mg2+]m, estimated using the
      fluorescent probe furaptra, averaged 0.67 mM in 15 preparations of beef heart
      mitochondria containing an average of 21 nmol total Mg2+ per mg protein. [Mg2+]m
      was compared with total Mg2+ during respiration-dependent uptake and efflux of
      Mg2+ and during osmotic swelling. In the absence of external Pi these
      mitochondria contain about 32 nmol/mg non-diffusible Mg-binding sites with an
      apparent Kd of 0.34 mM. [Mg2+]m depends on both the size of the total Mg2+ pool
      and the ability of matrix anions to provide Mg-ligands. Pi interacts strongly
      with Mg2+ to decrease [Mg2+]m and, in the absence of external Mg2+, promotes
      respiration-dependent Mg2+ efflux and a decrease in [Mg2+]m to very low levels.
      The uptake of Pi by respiring mitochondria converts delta pH to membrane
      potential (delta psi) and provides additional Mg-binding sites. This permits
      large accumulations of Mg2+ and Pi with little change in [Mg2+]m. Nigericin also
      converts delta pH to delta psi in respiring mitochondria and induces a large and
      rapid increase in both total Mg2+ and [Mg2+]m. Mersalyl increases the
      permeability of the mitochondrial membrane to cations and this also induces a
      marked increase in both total Mg2+ and [Mg2+]m. These results suggest that
      mitochondria take up Mg2+ by electrophoretic flux through membrane leak pathways,
      rather than via a specific Mg2+ transporter. Mitochondria swollen by respiration
      dependent uptake of potassium phosphate show decreased [Mg2+]m, whereas those
      swollen to the same extent in potassium acetate do not. This suggests that
      [Mg2+]m is well-buffered during osmotic volume changes unless there is also a
      change in ligand availability.

PMID- 9230924
TI  - Tracking prions: the neurografting approach.
AB  - The physical nature of the agent that causes transmissible spongiform
      encephalopathies (the 'prion'), is the subject of passionate controversy.
      Investigation of it has benefited tremendously from the use of transgenic and
      knockout technologies. However, prion diseases present several other enigmas,
      including the mechanism of brain damage and how the affinity of the agent for the
      central nervous system is controlled. Here we show that such questions can be
      effectively addressed in transgenic and knockout systems, and that pathogenesis
      may be clarified even before we can be certain about the nature of the infectious
      agent. Availability of mice overexpressing the Prnp gene (which encodes the
      normal prion protein) and Prnp knockout mice allows for selective reconstitution
      experiments aimed at expressing PrP in specific portions of the brain or in
      selected populations of hemato- and lymphopoietic origin. We summarize how such
      studies can offer insights into how prions administered to peripheral sites can
      gain access to central nervous tissue, and into the molecular requirements for
      spongiform brain damage.

PMID- 9230925
TI  - Intake of olive oil can modulate the transbilayer movement of human erythrocyte
      membrane cholesterol.
AB  - Transbilayer movement of erythrocyte membrane cholesterol is impaired in patients
      affected with essential hypertension. This is an inherited disorder, but
      environmental factors are also involved. Dietary fats might play a role in the
      prevention and/or treatment of such abnormality in the kinetic pools of membrane
      cholesterol. We tested this hypothesis by using a diet (in which 30% of the
      energy came from fat) rich in olive oil or in high-oleic sunflower oil (as
      natural sources of monounsaturated fatty acids, MUFAs) and determining their
      influence on the movement of cholesterol into the lipid bilayer of the
      erythrocyte membrane after a four-week period. We concluded that dietary olive
      oil is helpful in normalizing the impaired transbilayer movement of membrane
      cholesterol in erythrocytes of eight normocholesterolaemic and eight
      hypercholesterolaemic hypertensive patients. However, the effects cannot be
      attributed exclusively to the content of MUFAs (mainly oleic acid) in the diet,
      as high-oleic sunflower oil was unable to induce favourable changes.

PMID- 9230926
TI  - Biosynthetic pathway for producing the sex pheromone component (Z,E)-9,12
      tetradecadienyl acetate in moths involves a delta 12 desaturase.
AB  - Sex pheromones are used by insects as a form of chemical communication for the
      purpose of attracting conspecific mates. Female moths Cadra cautella and
      Spodoptera exigua use the diene (Z,E)-9,12-tetradecadienyl acetate as the major
      pheromone component. Biosynthesis of this pheromone component was demonstrated to
      occur through delta 11 desaturation of hexadecanoic acid (palmitate) to produce
      (Z)-11-hexadecenoic acid which is then chain-shortened to (Z)-9-tetradecenoic
      acid. A unique delta 12 desaturase uses the (Z)-9-tetradecenoic acid to produce
      (Z,E)-9,12-tetradecenoic acid which is reduced and acetylated to form the acetate
      ester pheromone component. Both moths also use a pheromonotropic peptide to
      stimulate pheromone biosynthesis.

PMID- 9230927
TI  - Annexins: what are they good for?
AB  - Annexins comprise a unique family of calcium- and phospholipid-binding proteins.
      At least one of the twenty members thus far described from this family can be
      found expressed in nearly every eukaryotic cell type. As common as these proteins
      may be, no one clear function for all has been established. Historically,
      individual members of this family have been given various names describing their
      ability to associate with a host of intra- and extracellular proteins and with
      cellular lipid membranes. The collection of reviews in this issue of CMLS
      represents an effort to offer a coordinated view of the research activities in
      the field and to extract structural and functional commonalities.

PMID- 9230928
TI  - Annexin gene structures and molecular evolutionary genetics.
AB  - Annexins provide an exemplary model for studying the pattern and process of
      molecular evolution in multigene families. Their related gene structures, broad
      dispersal in eukaryotic genomes and abundant coding sequences permit a
      phylogenetic reconstruction of their genetic history. The emerging picture is one
      of prolific expansion by gene duplication to more than 27 paralogous subfamilies
      that have undergone steady sequence divergence, speciation and differential
      selection. Homologous recombination via the common tetrad of internal repeats
      has, nevertheless, strictly preserved this core structure for over 1200 million
      years, implying a basic functional role. The existence of multiple annexins with
      unique 5' coding and regulatory regions has facilitated their adaptation to the
      varying ontogenetic and cell-specific needs of diverse organisms. Computational
      and cladistic sequence analyses have permitted the determination of original gene
      duplication dates and mutation rates for the ten known vertebrate annexins.
      Molecular genetic and evolutionary studies of annexins can help to define their
      structure-function relationships elucidate their individual physiological roles
      and ultimately link them to hereditary phenotypes.

PMID- 9230929
TI  - Three-dimensional structure of annexins.
AB  - Annexins constitute a family of structurally related calcium- and phospholipid
      binding proteins whose molecular structure has been investigated in detail in the
      crystalline and membrane-bound form. Their polypeptide chain is folded into four
      or eight alpha-helical domains of similar structure with a central hydrophilic
      pore. Bound to phospholipid membranes, the four-domain arrangement of the annexin
      molecule is conserved. A peripheral binding mode has been well documented by
      electron microscopy and a variety of other techniques.

PMID- 9230930
TI  - Participation of annexins in protein phosphorylation.
AB  - Simultaneous discovery of members of the annexin family of calcium and
      phospholipid binding proteins by several groups is intimately linked to the
      possibility that these proteins may be controlled by phosphorylation. Indeed,
      annexin I and annexin II have been identified as major substrates for the
      tyrosine kinase activity associated with epidermal growth factor receptor (EGF-R)
      and for the retrovirus encoded protein tyrosine kinase pp60v-arc. Both annexins
      are also in vitro and/or in situ substrates for platelet derived growth factor
      (PDGF), insulin and hepatocyte growth factor/scatter factor (HGF/SF) receptor
      tyrosine kinases. In addition, to serve as substrates for tyrosine protein
      kinases some annexins are cellular targets for serine threonine protein kinases
      such as protein kinase C (PKC) and cAMP-dependent protein kinase A (PKA).
      Although the role of annexin phosphorylation has not been studied in detail, it
      is thought to influence their vesicle aggregation and phospholipid binding
      properties. Some annexins are also potent inhibitors of various serine/threonine
      and tyrosine kinases. The physiological functions of the annexins have still not
      been clearly defined. Therefore the identification of the ability of these
      proteins to undergo phosphorylation may be helpful in assigning them a precise
      biological role.

PMID- 9230931
TI  - Annexin V, the regulator of phosphatidylserine-catalyzed inflammation and
      coagulation during apoptosis.
AB  - Annexin V belongs to a family of phospholipid binding proteins, the Annexins. It
      binds in the presence of Ca(2+)-ions with high affinity to negatively charged
      phospholipids like phosphatidylserine (PS). On the basis of its protein structure
      and biological activity Annexin V is considered as a protein exhibiting its
      hitherto unknown function within the intracellular environment. One argument
      comes from the understanding that PS is predominantly located in membrane
      leaflets, which face the cytosol. However, recent findings show that each cell
      type has the molecular machinery to expose PS at its cell surface. This machinery
      is activated during the execution of apoptosis. Once PS is exposed at the cell
      surface it exhibits procoagulant and proinflammatory activities. Annexin V will
      bind to the PS-exposing apoptotic cell and can inhibit thereby the procoagulant
      and pro-inflammatory activities of the dying cell. These findings together with
      the presence of Annexin V in the extracellular space depict a novel
      (patho)Physiological significance for Annexin V in vivo.

PMID- 9230932
TI  - Annexins in the secretory pathway.
AB  - Among the multiplicity of roles suggested for proteins of the annexin family,
      those implicating these proteins in regulated exocytosis remain among the most
      convincing. Studies in this area of annexin biology have focused on annexin II,
      which because of its unusually low Ca(2+)-requirement for phospholipid-binding
      has many of the requisite properties of a membrane fusogenic Ca2+ sensor. Other
      annexins are also good candidates for exocytotic mediators, especially annexins I
      and VII, which have strong vesicle-aggregating activities. In contrast, annexin
      VI appears to block vesicle aggregation, perhaps acting as a negative regulator
      of exocytosis. In this review, we consider the evidence for and against annexins
      having functions in the secretory pathway.

PMID- 9230933
TI  - Annexin V interactions with collagen.
AB  - Annexin V was originally identified as a collagen-binding protein called anchorin
      CII and was isolated from chondrocyte membranes by affinity chromatography on
      native type II collagen. The binding of annexin V to native collagen type II is
      stable at physiological ionic strength when annexin V is reconstituted in
      liposomes. The binding to native collagen types II and X, and to some extent to
      type I as well, was confirmed using recombinant annexin V. A physiological role
      for annexin V interactions with extracellular collagen is consistent with the
      localization of annexin V on the outer cell surface of chondrocytes, microvilli
      of hypertrophic chondrocytes, fibroblasts and osteoblasts. A breakthrough in our
      understanding of the function of annexin V was made with the discovery of its
      calcium channel activity. At least one of several putative functions of annexin V
      became obvious from studies on matrix vesicles derived from calcifying cartilage.
      It was found that calcium uptake by matrix vesicles depend on collagen type II
      and type X binding to annexin V in the vesicles and was lost when collagens were
      digested with collagenase: calcium influx was reconstituted after adding back
      native collagen II or V. These findings indicate that annexin V plays a major
      role in matrix vesicle-initiated cartilage calcification as a collagen-regulated
      calcium channel.

PMID- 9230935
TI  - Annexins in cancer and autoimmune diseases.
AB  - Several annexins have been implicated in the pathogenesis of benign and malignant
      neoplasms of different origins. In some tumours a suppressive action of annexins
      has been shown, whereas studies of other tumours indicate an involvement of
      annexins in tumour progression. In the light of the expression of annexins at
      distinct episodes of fetal development these observations point towards a
      functional role of annexins in cellular development and differentiation. This
      view is supported by data that link certain annexins to distinct pathways of
      signal transduction. Auto-antibodies against several annexins have been detected
      in patients with autoimmune diseases such as systemic lupus erythematosus,
      rheumatoid arthritis and inflammatory bowel disease. Until now it is unclear
      whether their presence reflects a relevant pathogenetic mechanism or merely
      represents an unspecific expression of a raised autoimmunity in these patients.

PMID- 9230934
TI  - Structures and functions of annexins in plants.
AB  - The first evidence that higher plants contain annexins was presented in 1989.
      Since that time, annexins have been purfied and characterized from a variety of
      plant sources. Analyses of the deduced proteins encoded by annexin cDNAs indicate
      that the majority of these plant annexins possess the characteristic four repeats
      of 70 to 75 amino acids and possess motifs proposed to be involved in Ca2+
      binding. Like animal annexins, plant annexins bind Ca2+ and phospholipids and are
      abundant proteins, but there are indications that the number of distinct plant
      annexin genes may be considerably fewer than that found in animals. Regarding
      function, a number of studies show that various members of the annexin family of
      plants may play roles in secretion and/or fruit ripening, show interaction with
      the enzyme callose (1.3-beta-glucan) synthase, possess intrinsic nucleotide
      phosphodiesterase activity, bind to F-actin, and/or have peroxidase activity.

PMID- 9230936
TI  - Clinical outcome of digital replantation using the fibrin glue-assisted
      microvascular anastomosis technique.
AB  - A series of 36 digital replants is reported in which microvascular anastomoses
      were each performed with four to six stitches and topically applied fibrin glue.
      Thirty-two digits survived, comparable to survival with conventional
      microvascular anastomosis. The average operative time per replanted digit was 3.2
      hours, considerably less than documented with standard replantation technique
      (4.5 hours per digit). These clinical findings indicate that fibrin glue-assisted
      microvascular anastomosis does not compromise replant outcome and can reduce the
      operative time by reducing the number of microsutures that need to be placed in
      each anastomosis.

PMID- 9230937
TI  - Replantation-revascularization and primary amputation in major hand injuries.
      Resources spent on treatment and the indirect costs of sick leave in Sweden.
AB  - Thirty consecutive patients with amputation or devascularizing injuries of the
      thumb or two or more fingers proximal to the PIP joint were reviewed.
      Replantation or revascularization had been done in 27 patients, in 24
      successfully. Three patients had primary amputation. The distribution of
      calculable costs was dominated by those for sick leave (49%), operation (26%) and
      ward costs (20%). Out-patient care, physiotherapy and travel together constituted
      only 6%. The cost of a successful replantation was equal to 1.6 times the mean
      annual salary of these patients and that of primary amputation about half as
      much. Mobility, power and performance of a standardized grip test were better for
      the successfully replanted or revascularized patients. Subjective evaluation of
      23 parameters of function, cosmesis and quality of life did not disclose any
      differences. All patients except three had returned to their original work within
      2 years.

PMID- 9230938
TI  - Functional anatomy of the triangular fibrocartilage complex.
AB  - The functional anatomy of the triangular fibrocartilage complex (TFCC) was
      investigated in 20 fresh cadavers. Dynamic changes in the TFCC during rotation
      were also examined from both the proximal and distal aspects. In our analysis,
      the TFCC was separated into three components. The distal component was stable,
      functioning like a hammock to suspend the ulnar carpus. The proximal component
      was the fan-shaped triangular ligament, the true radioulnar ligament. This was
      found to originate from the fovea of the ulna in a vertical fashion and was
      easily twisted during rotation. The third component, the ulnar collateral
      ligament, also twisted during rotation. When analysed by coronal section, the
      internal portion of the TFCC was found to be loose, and probably serves as a
      cushion to absorb local deformities in the TFCC during rotation.

PMID- 9230939
TI  - A cadaveric study of the anatomy and stability of the distal radioulnar joint in
      the coronal and transverse planes.
AB  - Fifty preserved cadaver wrist specimens were studied. The anatomy of the distal
      radioulnar joint is complex, with varying configurations in the transverse and
      midcoronal planes. There is disparity in the radii of curvature of the sigmoid
      notch and the ulna-articular surface in the transverse plane, with resultant
      articular incongruity. Motion at the distal radioulnar joint is, hence, likely to
      be a combination of sliding and rotation with a small area of true appositional
      contact. The palmar osteocartilaginous lip of the sigmoid notch, along with the
      interosseous membrane, may be of importance in distal radioulnar stability.
      Palmar and dorsal radioulnar ligaments may act as "check-rein" ligaments,
      especially when seen with the "flat face" (type A) sigmoid notch.

PMID- 9230940
TI  - Venous pumps of the hand. Their clinical importance.
AB  - Oedema remains one of the most common causes of hand stiffness. Local venous
      return is intimately associated with oedema formation and management. To
      elucidate the underlying mechanisms of venous return, the venous pumping systems
      in the hand were objectively and quantitatively investigated using Doppler
      ultrasound, cadaveric dissection and venography. It was demonstrated that
      functionally there are three independent venous systems: the superficial palmar,
      deep palmar and dorsal veins, which are activated by palm compression, isometric
      intrinsic muscle contraction, and dorsum compression, respectively. Each system
      was investigated independently and found to increase venous blood velocity in
      both the cephalic and ulnar veins. These systems were also shown to act in
      synergy, producing the greatest velocity increase when concurrently activated
      during fist-clenching. The volume of blood pumped during fist-clenching could
      also be potentiated by preloading by digit abduction. The clinical applications
      of these findings are discussed.

PMID- 9230941
TI  - A new technique for the assessment of wrist movement using a biaxial flexible
      electrogoniometer.
AB  - A new electrogoniometer technique is described for the measurement of wrist
      movements, including circumduction, with the results being displayed as figures.
      Clinical validation has been performed and the system found to be highly accurate
      and reliable. Applications of the technique are illustrated. It is suggested this
      technique should in the future be used to assess wrist movement in clinical and
      research applications.

PMID- 9230942
TI  - The motion analysis system and the maximal area of fingertip motion. A
      preliminary report.
AB  - We have used the motion analysis system to evaluate the maximal area of fingertip
      motion. Some modification in setting the cameras and use of a smaller marker is
      required. In this series, 58 examinations have been accomplished on 28 fingers
      with various traumatic injuries. The closed curve derived from the motion
      analysis system and the area calculated from it were easier to interpret and
      could be compared in serial examinations. A high linear correlation between the
      fingertip motion area and total active motion was found. The computer-aided
      motion analysis system complements the traditional methods of assessing an
      injured finger.

PMID- 9230943
TI  - Congenital triggering of the index finger at the A2 pulley.
AB  - A case of trigger index finger is reported. The diagnosis was made in the
      neonatal intensive care unit. The proximal interphalangeal joint (PIP) was locked
      in a flexed position. A nodular thickening of the flexor tendon was felt at the
      A2 pulley level. Surgery revealed thickening of both the A2 pulley and the radial
      slip of the flexor superficialis tendon. Division of the A2 pulley released the
      PIP joint locking.

PMID- 9230944
TI  - "Congenital" trigger thumb caused by intratendinous granulation tissue.

PMID- 9230945
TI  - Diagnosis of closed central slip injuries. A cadaveric analysis of non-invasive
      tests.
AB  - Four non-invasive tests for central slip integrity were analysed using 20 fresh
      frozen cadaver fingers. A pre-boutonniere deformity was simulated by dividing the
      central slip. A passively correctable boutonniere was simulated by dividing the
      central slip, triangular ligament and oblique fibres of the extensor expansion.
      The test described by Boyes, which evaluates distal interphalangeal joint
      flexion, was found not to be reliable for the diagnosis of either injury. The
      test described by Elson, which evaluates distal interphalangeal joint rigidity
      while actively extending the flexed proximal interphalangeal joint, was the only
      manoeuvre which was able to discern central slip integrity in both simulated
      injuries. The central slip tenodesis test and testing resistance of active
      proximal interphalangeal joint extension should be performed with the proximal
      interphalangeal joint in flexion to weaken the effectiveness of the lateral
      bands.

PMID- 9230946
TI  - Extensor indicis opposition transfer in the ulnar and median palsied thumb in
      leprosy.
AB  - Twenty seven opponensplasties for ulnar and median paralysis in 25 leprosy
      patients were performed using extensor indicis proprius. An additional transfer
      of the radial half of flexor pollicis longus to extensor pollicis longus was done
      to stabilize the metacarpophalangeal joint of the thumb. The biomechanical
      aspects of extensor indicis proprius tendon transfer were studied and results
      evaluated using various anatomical and functional parameters. Extensor indicis
      proprius provides adequate strength to position the thumb. However, sometimes it
      does not reach its new insertion. There is no significant deficit at the donor
      site but in a few cases the index finger may lose its capability for independent
      extension and sometimes a proximal interphalangeal joint contracture may develop.

PMID- 9230947
TI  - Evaluation of the results of opponensplasty.
AB  - A comprehensive evaluation system for opponensplasties has been described taking
      into consideration several variables. Each variable has been assigned a score
      depending upon its significance in the normal hand. The total score of the hand
      is used for grading the results as good, fair and poor.

PMID- 9230948
TI  - Flexor tendon repair in zone 2 followed by early active mobilization.
AB  - The results following primary and delayed primary repair in zone 2 flexor tendon
      injuries were evaluated prospectively in 88 fingers of 71 patients using two
      different early postoperative mobilization programmes. In 33 patients, the
      Kleinert rubber band passive flexion method was used. In the remaining 38
      patients, the early active mobilization programme was used. All patients were
      reviewed 1 year after operation and the results assessed by the Strickland
      criteria. During this evaluation maximum grip strength was also measured. The
      results were excellent or good in 78% of digits and mean grip strength was 84% of
      the uninjured hand in the Kleinert rubber band passive flexion group. In the
      early active mobilization group, excellent or good results were achieved in 85%
      of the digits and the mean grip strength was 90% of the uninjured hand. There
      were two early ruptures in each group.

PMID- 9230949
TI  - A new technique of attachment of flexor tendons to the distal phalanx without a
      button tie-over.

PMID- 9230950
TI  - Restoration of metacarpophalangeal extension of the thumb in inflammatory
      arthritis.
AB  - Nine patients (11 cases) with inflammatory arthritis who had an early boutonniere
      deformity of the thumb treated by rerouting of the extensor pollicis longus
      tendon were reviewed. Preoperatively, all patients complained of pain, disability
      in activities of daily living and extensor lag of the MP joint ranging from 10 to
      60 degrees. At a mean follow-up of 38 months, nine thumbs had equal active and
      passive MP joint extension. Two thumbs had a moderate extensor lag. Functional
      strength assessment demonstrated no deleterious effect of the procedure in the
      operated compared to the non-operated thumb. Subjectively, all patients but one
      were satisfied. This procedure appeared to correct or to limit the progression of
      the deformity. A deficit of interphalangeal extension in five patients may
      require a modification of the procedure to tighten the extensor pollicis longus
      distal to the MP joint.

PMID- 9230951
TI  - An unreported cause of rupture of the extensor pollicis longus tendon.
AB  - Avulsion fractures of the index metacarpal at the insertion of extensor carpi
      radialis longus are rare. We report such a fracture and the resulting
      complication of division of the extensor pollicus longus tendon, by the avulsed
      bony fragment. Careful clinical assessment and appropriate radiological
      examination is needed to diagnose this rare fracture and internal fixation is
      recommended.

PMID- 9230952
TI  - Matrix synthesis and cell proliferation in repaired flexor tendons within e-PTFE
      reconstructed flexor tendon sheaths.
AB  - Expanded polytetrafluoroethylene (e-PTFE) may be used as a barrier to reduce
      formation of restrictive adhesions following tendon surgery within the flexor
      tendon sheath region. In order to assess its effects on the cellular activity of
      healing tendons, synthesis and contents of matrix components and synthesis of DNA
      were compared in divided and sutured flexor tendons that either had been covered
      with e-PTFE membranes or with sham-operated tendon sheaths in 30 rabbits. At
      intervals of up to 12 weeks segments of the tendon repair sites were harvested,
      placed in wells and labelled with 35S-sulphate, 3H-proline and 3H-thymidine
      during short-term culture in vitro. Adverse tissue reactions and tendon
      disruptions were not observed at harvest. At each time interval synthesis of
      matrix components and DNA and contents of protein and collagen in the repaired
      tendon segments were similar in the two groups. Measured over all intervals,
      synthesis of non-collagen protein and contents of protein and collagen were lower
      in the e-PTFE groups. These results show that reconstruction of flexor tendon
      sheaths with e-PTFE membranes may not significantly impair cell proliferation but
      to some extent may reduce protein synthesis of healing tendons.

PMID- 9230953
TI  - Arthrogryposis multiplex congenita in a monozygotic twin. An intrauterine lesion?
AB  - Arthrogryposis multiplex congenita is a specific, well-defined congenital
      deformity which primarily affects muscles of limbs resulting in secondary joint
      deformities. The aetiology is still uncertain. One of monozygotic twin brothers
      with classical arthrogryposis multiplex congenita is presented, proving that this
      specific condition is not genetically transmitted.

PMID- 9230954
TI  - Finger duplication in Apert's syndrome.
AB  - Three cases of unilateral duplication of the little finger in children with
      Apert's syndrome are presented. They provide additional evidence that the hands
      in Apert's syndrome are not always symmetrically affected.

PMID- 9230955
TI  - Extremity gangrene in utero.
AB  - A neonate with extremity gangrene resulting from intrauterine embolization of
      infarcted placental substances is discussed. This rare clinical entity is thought
      to be most commonly a manifestation of embolic phenomenon during maturation of
      the neonatal circulatory system. Management of neonatal gangrene is conservative,
      delaying amputation as long as possible since the line of demarcation tends to
      migrate distally. Evidence of multiple emboli should be carefully sought prior to
      definitive treatment.

PMID- 9230956
TI  - Idiopathic multicentric osteolysis principally affecting the phalanges of the
      hands and feet.
AB  - The case of a 64-year-old man with idiopathic symmetrical osteolysis affecting
      both hands and feet is presented. The phalanges were principally affected, with
      relative sparing of the carpus and tarsus. The relevant literature has been
      reviewed and this reveals that the distribution of osteolysis in this case is
      unique. We suggest that this case represents a different disease entity, which
      has not been described previously.

PMID- 9230957
TI  - Selective reinnervation of regenerating mixed nerve fibres across a silicone tube
      gap. Further experimental evidence of neurotropism.
AB  - This study investigated specific regeneration of a mixed motor and sensory nerve
      by the method of spinal dorsal root ganglions resection. A 10 mm segment of
      tibial nerve was resected and the nerve ends inserted in a silicone tube.
      Fourteen weeks later, dorsal root ganglia from L6 to S1 were resected on the
      experiment side. Twenty weeks later, the regenerating motor nerve fibres of mixed
      nerves selectively grew into motor branches. The rate of misdirected growth in
      mixed nerves was less than 6%. These results suggest that regenerating motor and
      sensory axons of mixed nerves are able to select their distal target organs
      accurately. Better results may be obtained using the entubulation repair method.

PMID- 9230958
TI  - Pressure changes in Guyon's canal after carpal tunnel release.
AB  - We measured pressure changes in Guyon's canal and the carpal tunnel before and
      after endoscopic (11 cases) and open (10) carpal tunnel release. We found that
      release of the flexor retinaculum by endoscopic and open techniques measurably
      decreased pressure in both the carpal tunnel and Guyon's canal. This study
      provides an explanation for relief of ulnar tunnel syndrome symptoms following
      carpal tunnel release and may indicate that carpal tunnel release alone may be
      sufficient to provide symptomatic relief for most patients with carpal and ulnar
      tunnel syndromes.

PMID- 9230959
TI  - Compression neuropathy of the palmar cutaneous branch of the median nerve by the
      antebrachial fascia.
AB  - An isolated compression neuropathy of the palmar cutaneous branch of the median
      nerve is described in a woman who presented with a small tender mass over the
      anterior aspect of her distal forearm and complete numbness over the thenar
      eminence. Surgical exploration revealed thickening of the palmar cutaneous nerve
      as it passed upwards through the antebrachial fascia on the ulnar aspect of the
      flexor carpi radialis tendon. Neurolysis of two separate fascicles of the palmar
      cutaneous branch of the median nerve and excision of a window of antebrachial
      fascia resulted in complete return of sensation over the thenar eminence.

PMID- 9230960
TI  - Complete endoscopic carpal tunnel release in long-term haemodialysis patients.
AB  - The roof of the carpal tunnel (or canal) consists of the distal portion of the
      flexor retinaculum, the flexor retinaculum (or the transverse carpal ligament)
      and the proximal portion of the flexor retinaculum. We tried to determine which
      anatomical structures were relevant to complete endoscopic carpal tunnel
      decompression in long-term haemodialysis patients with carpal tunnel syndrome.
      Carpal tunnel pressure was measured using the continuous infusion technique
      before and after endoscopic release of the flexor retinaculum, distal portion of
      the flexor retinaculum and the proximal portion of the flexor retinaculum
      respectively in 257 hands. We concluded that release of the distal portion of the
      flexor retinaculum, in addition to the flexor retinaculum, is essential for
      complete carpal tunnel decompression in long-term haemodialysis patients.

PMID- 9230961
TI  - A severe infection following endoscopic carpal tunnel release.
AB  - A 59-year-old patient underwent endoscopic carpal tunnel release by Chow's two
      portal technique. He developed a pyogenic tenosynovitis and an infection within
      the ulnar and radial bursae, an abscess in the middle palmar, thenar and Parona's
      space, and a pyogenic wrist arthritis. Surgical treatment included a wide
      exposure of the infected region, debridement, irrigation, application of a
      resorbable collagen sponge containing gentamicin, insertion of two drains and
      primary wound closure. The infection was brought under control and hand function
      restored.

PMID- 9230962
TI  - Total middle ray amputation.
AB  - Eight patients underwent middle ray amputation with excision of the whole of the
      middle metacarpal and careful soft tissue repair. Excision of the base of the
      middle metacarpal allowed easier approximation of the index and ring rays without
      the tendency of these fingers to either scissor on finger flexion or to remain
      slightly apart. Complete removal of the middle metacarpal appears to allow the
      bases of the index and ring metacarpals to migrate together. The removal of the
      metacarpal base caused no functional problems and the technique created a good
      three-finger hand from both a functional and cosmetic point of view.

PMID- 9230963
TI  - Hand trauma and herpes infection.
AB  - A herpes simplex type 2 infection of the hand after injury is described in a 26
      year-old man. The management and implications of such an unusual hand infection
      are discussed.

PMID- 9230964
TI  - Giant cell tumours of the hand.
AB  - A study of seven cases of giant cell tumours of the hand is reported. All tumours
      were treated by an en bloc excision of the tumour or by whole ray resection. En
      bloc resection of the tumour and reconstruction with a fibular graft where
      necessary should be considered as the treatment of choice in giant cell tumour of
      the hand.

PMID- 9230965
TI  - Osteoid osteoma of the radial diaphysis.
AB  - We report a case of osteoid osteoma of the radial diaphysis. Excision of the
      nidus relieved pain.

PMID- 9230966
TI  - Myxoma of the hand.
AB  - A rare case of myxoma of the dorsal aspect of the little finger is described.
      Classification of myxomas of the upper limb is discussed.

PMID- 9230967
TI  - A small cavernous vascular malformation in the hand mimicking a glomus tumour.
AB  - A case of a subcutaneous haemangioma of the hand clinically mimicking a glomus
      tumour is described. Other discrete small hand tumours that may present with the
      triad of pain, tenderness and cold intolerance are discussed.

PMID- 9230968
TI  - Brachial plexus palsy and carotid artery dissection.
AB  - We report a case of stroke due to carotid artery dissection in a young man
      following a traumatic brachial plexus palsy associated with a pseudoaneurysm of
      the axillary artery.

PMID- 9230969
TI  - Long-term follow-up of 50 Duke silicone prosthetic fingers.
AB  - Thirty-three patients with single and multiple digital amputations were fitted
      with a total of 50 prosthetic silicone fingers over a mean period of 4 years. The
      prosthetic fingers were custom made using a special method which has been
      modified at our institution. This study provides a detailed analysis of patients'
      occupational and cosmetic usage of and satisfaction with their prostheses, as
      well as describing the fabrication technique.

PMID- 9230971
TI  - Occupation as a risk factor for impaired sensory conduction of the median nerve
      at the carpal tunnel.

PMID- 9230970
TI  - Return to work after endoscopic and open carpal tunnel decompression.

PMID- 9230972
TI  - Non-puerperal induced lactation in a Nigerian community: case reports.
AB  - Six Nigerian women aged from 22 to 56 years who had not recently been pregnant
      were successfully relactated by breast suckling alone. All of them produced
      enough milk to exclusively breastfeed 'motherless' infants. All except one child
      have continued to breastfeed up to the time of this report and show adequate
      growth.

PMID- 9230973
TI  - Epidemiology of influenza virus infections in children with acute respiratory
      infections in Zambia.
AB  - A viral aetiological and epidemiological study of acute respiratory infections
      (ARI) in children was carried out in Lusaka, Zambia between June 1993 and
      September 1995. A total of 3,760 throat swab specimens were collected for virus
      isolation from children under 5 years of age who had ARI and were attending three
      health centres in Lusaka. Between June and November 1993, 52 cases of the
      influenza A/H3N2 viruses were isolated. Between May and July 1994, 34 influenza B
      cases were isolated. In 1995, one A/H3N2 influenza virus was isolated in January
      and then the same type of influenza virus was isolated from 55 samples between
      June and August. The isolation rate of influenza virus was highest at 14.3%
      (20/139) in August 1993, at 15.1% (18/119) in June 1994 and at 25.4% (43/169) in
      July 1995. This is the first report of a consecutive study of influenza virus
      infections in Zambia and the results reveal that influenza virus infections are
      one of the most important pathogens of ARI in children in the cool, dry season
      (June-August) in this country.

PMID- 9230974
TI  - Pneumocystis carinii pneumonia in Malawian children.
AB  - Sixty children aged between 1 and 23 months admitted to Queen Elizabeth Central
      Hospital in Blantyre, Malawi for diagnosis of acute lower respiratory tract
      infections (ALRI) were investigated for laboratory diagnosis of Pneumocystis
      carinii pneumonia (PCP) by indirect immunofluorescence assay on nasopharyngeal
      secretions. P. carinii was found in five of the 60 children. Three PCP cases had
      AIDS. The clinical presentation of children with PCP was of little diagnostic
      value and all the children were infants. Arterial oxygen saturation was
      significantly lower in PCP cases. Of the five PCP cases, four died, indicating
      that the marked hypoxaemia was associated with poor prognosis. These results
      indicate that an immunofluorescence assay on nasopharyngeal secretions could be
      used for first-line diagnosis of PCP in Africa.

PMID- 9230975
TI  - Acute lower respiratory tract infections in children in Kuwait.
AB  - The features of community-acquired acute lower respiratory tract infections in
      390 children are described. Half (50%) presented with bronchiolitis, 37% with
      pneumonia and 13% with croup. Respiratory syncytial virus was the commonest agent
      identified (52% of bronchiolitis, 29% of pneumonia, 51% of croup). Positive
      bacterial blood cultures were obtained in 10% of the patients, all except one
      with pneumonia. Fever (> 39 degrees C), a toxic ill look, bronchial breathing,
      WCC > 20 x 10(9)/l, neutrophils > 5 x 10(9)/l, platelet count > 500 x 10(9)/l,
      ESR > 45 mm/hr, lobar consolidation and pleural effusion were more likely to be
      associated with bacterial than with viral pneumonia (relative risk > 1.81; p <
      0.05). In areas with limited resources, a high fever, a toxic ill look, bronchial
      breathing and simple laboratory tests may help to identify patients with
      bacterial pneumonia.

PMID- 9230976
TI  - Ulceration of a previously healed BCG scar in suspected disseminated BCG
      infection.
AB  - A 2.5-year-old boy with disseminated tuberculosis, highly suspected to be
      disseminated BCG infection which occurred against a background of secondary
      immunodeficiency due to measles and malnutrition, is presented. The initial
      diagnosis was post-measles bronchopneumonia, meningitis and marasmus. The final
      diagnosis was arrived at only because of a high clinical index of suspicion of
      tuberculosis which is needed in all communities with a high prevalence of
      tuberculosis. The absence of AIDS and the extreme rarity of ulceration of a
      previously healed BCG scar are noted.

PMID- 9230977
TI  - The clinical manifestations of cerebral malaria among Nigerian children with the
      sickle cell trait.
AB  - In order to describe the interaction between haemoglobin type and the clinical
      manifestations of cerebral malaria, we studied 60 children aged between 6 and 60
      months at University College Hospital, Ibadan, Nigeria. Haemoglobin AS
      individuals with cerebral malaria did not exhibit major differences in clinical
      and laboratory characteristics when compared with their haemoglobin AA
      counterparts. There were no deaths among the Hb AS children compared with an 18%
      mortality in the Hb AA group. Blood transfusion rates were higher in the AS than
      in the AA children (86% vs 44%). The higher transfusion rates in the AS group is
      consistent with in-vitro observations of sickling of parasitized red cells
      containing Hb S which in vivo would be cleared by the reticuloendothelial system.
      It is concluded that the clinical manifestations of cerebral malaria are
      essentially similar in children with haemoglobins AS and AA but the former have
      higher transfusion needs and are less likely to die.

PMID- 9230978
TI  - Lead levels in deciduous teeth of children in Bahrain.
AB  - To determine lead exposure among children in Bahrain, a total of 280 shed
      deciduous whole teeth were collected from 269 children. Teeth were analyzed for
      lead concentrations using atomic absorption spectrophotometry with electrothermal
      atomization. Children were between 5 and 15 years old. The study period extended
      from July 1993 to April 1994. The study showed that the overall mean tooth-lead
      level was 4.3 micrograms/g dry weight with a range of 0.1-60.8 micrograms/g dry
      weight. The cumulative frequency distribution revealed that 35% of the teeth had
      a lead concentration of more than 4 micrograms/g dry weight. The tooth-lead
      concentrations differed according to the tooth type age. The child's sex,
      nationality, area of residence and socio-economic status had no impact on tooth
      lead level. In conclusion, lead is present in toxic concentrations in 35% of the
      teeth of the children studied. Urgent measures are needed to eliminate lead from
      gasoline, paint and other sources in the environment.

PMID- 9230979
TI  - Consanguineous marriages in a Saudi population and the effect of inbreeding on
      prenatal and postnatal mortality.
AB  - Consanguineous marriages are strongly favoured in the Saudi population. A
      population-based study of consanguineous marriages was conducted in the Riyadh
      area. The prevalence rate of consanguineous marriages was 51.3% with an average
      inbreeding coefficient of 0.02265, which is high compared with many other
      countries. The most important variables affecting inbreeding were the regional
      background of the family (p < 0.001) and the level of education, which was
      inversely associated with consanguineous marriage (p < 0.001). Perinatal and
      postnatal mortalities were not significantly different between consanguineous and
      non-consanguineous families.

PMID- 9230980
TI  - Invasive retroperitoneal infection due to Basidiobolus ranarum with response to
      potassium iodide--case report and review of the literature.
AB  - We report a case of invasive retroperitoneal zygomycotic infection caused by
      Basidiobolus ranarum in a healthy 8-year-old boy. The youngster responded
      dramatically to potassium iodide. The clinical and pathological features are
      reviewed to highlight the problems encountered in the management of this rare
      infection.

PMID- 9230981
TI  - Cryptococcal meningitis in African children.
AB  - Three cases of cryptococcal meningitis in Malawian children aged 6 weeks, 3 years
      and 9 years are described. Only 23 cases of cryptococcal meningitis in children
      have been described previously, but in children from Europe and the USA. These
      are therefore the first cases of cryptococcosis to be described in African
      children.

PMID- 9230982
TI  - Hypertension and acute renal failure in Nigerian children with Burkitt's
      lymphoma: report of three cases and review.

PMID- 9230983
TI  - Intraosseous infusion in an emergency situation: a case report.
AB  - An 18-month-old boy who had cardiopulmonary arrest secondary to penicillin
      anaphylaxis was successfully resuscitated by intraosseous administration of
      emergency resuscitative medications because peripheral vascular access was
      impossible. He was discharged 2 weeks later in a satisfactory clinical condition.

PMID- 9230985
TI  - [Therapeutic non-compliance: hard truth to say or hard truth to hear?].

PMID- 9230984
TI  - Inaccuracy of the Schwartz formula in estimating glomerular filtration rate in
      Nigerian children.
AB  - The accurate estimation of renal function is of vital importance in the
      management of a child with renal disease. Given the well known difficulties of
      obtaining an accurately timed 24-hour urine sample from children and lacking the
      resources for estimating glomerular filtration rate (GFR) using radionuclide
      methods, the clinician practising in a developing country often has to resort to
      the use of height/plasma creatinine formulae when a rapid assessment of GFR is
      needed. In order to assess the accuracy of one of the better known formulae
      (Schwartz formula) in predicting GFR, 34 children with the nephrotic syndrome and
      30 apparently healthy children with no evidence of renal disease were studied at
      the University College Hospital, Ibadan. Two methods, Altman-Bland analysis and
      correlation coefficients, were used to assess agreement between measured GFR (by
      endogenous creatinine clearance) and GFR estimated by formula. The results show
      that the height/plasma creatinine formula of Schwartz et al. is a poor predictor
      of GFR as measured by endogenous creatinine clearance in Nigerian children and
      that it overestimated GFR in over two-thirds of the children. These observations
      may be due to differences in the constant, k, in the formula, which was found to
      vary widely in this study with a mean value of 0.45 compared with 0.55 in the
      formula. It is suggested that height/creatinine formulae for predicting GFR be
      tested and validated for accuracy in a given environment before routine use in
      clinical settings.

PMID- 9230986
TI  - [Elective phagocytosis of polynuclear neutrophils caused by medullary macrophages
      and autoimmune neutropenia in children].
AB  - Autoimmune neutropenia (AIN) is a frequent cause of chronic neutropenia
      especially in youngest children. Its diagnosis is established by immunological
      proof of the autoimmune mechanism. The aim of this study is to better describe
      this autoimmune process and to show the contribution of bone marrow smears to
      this diagnosis. PATIENTS AND METHODS: Ten children, six girls and four boys, were
      examined between 1990 and 1995. Eight of them had typical AIN, confirmed by the
      presence of antibodies against neutrophils. Two other patients were included on
      the basis of bone marrow pictures. Five non-neutropenic children with normal bone
      marrow smears were chosen as controls. Bone marrow analysis was always performed
      by the same cytologist according to a reproducible technique. RESULTS: Six out of
      ten patients had important features of elective phagocytosis of neutrophils by
      marrow macrophages (unlike controls) without signs of dysgranulopoiesis or
      hemophagocytosis. Antibodies against neutrophils were detected in six patients
      with phagocytosis and in four patients without these cytological features. In two
      other children presenting the same bone marrow picture and clinical profile, an
      autoimmune process was probable, even in the absence of antibodies against
      neutrophils. Some patients had several infections and were given immunoglobulins
      and/or granulocyte colony-stimulating factor (G-CSF) therapy. The efficacy of
      Immunoglobulin was not constant, whereas G-CSF was effective at low doses and
      shortened the duration of infections. CONCLUSION: Prolonged neutropenia in
      childhood must lead to look for phagocytosis by marrow macrophages in bone marrow
      smears, as a possible sign of autoimmunity. Growth factors may temporarily be
      used associated with antibiotics therapy in severe and prolonged infections.

PMID- 9230987
TI  - [Diagnostic value of granulocyte elastase determination in cord blood of newborn
      infants at risk for maternofetal infection].
AB  - BACKGROUND: Polymorphonuclear elastase is an early and sensitive indicator of
      neonatal infection when performed at the beginning of clinical symptoms. PATIENTS
      AND METHODS: To investigate the diagnostic value of elastase measurement in cord
      blood immediately after birth, 211 neonates (103 boys vs 108 girls, 154 vaginal
      delivery vs 57 cesarean section). Mean gestational age 38.9 weeks (range: 30-42),
      mean birth weight 3,260 g (range: 1,430-4,920 g). After clinical, bacterial and
      biological screening, the infants were classified in three groups. Group A (n =
      118): none infectious risk factor neither clinical signs of infection; group B (n
      = 79): one or more risk factors but no evidence of infection; group C (n = 14):
      proved or probable infection. Polymorphonuclear elastase was measured in cord
      blood of all infants using an heterogeneous enzyme-linked-immunosorbent assay.
      RESULTS: We observed higher elastase values in group C (176 +/- 67 micrograms/L)
      than in group A (91 +/- 64 micrograms/L) and B (67 +/- 61 micrograms/L) (mean +/-
      SD, P = 0.0001). With a cutoff value fixed at 80 micrograms/L, the sensitivity of
      this test applicated to neonates presenting materno-fetal infectious risk
      factor(s) was 85% (12/14), specificity 74% (59/79), positive predictive value
      37%, and negative predictive value 96%. CONCLUSION: Because two of the 14
      infected infants (15%) were not detected by elastase dosage in cord blood, this
      test cannot be used as an early indicator of materno-fetal infection.

PMID- 9230988
TI  - [Post-natal diagnostic strategy of urinary tract malformations detected by
      prenatal screening].
AB  - BACKGROUND: The increasing experience with prenatal ultrasonographic diagnosis
      allows detection of more and more mild urinary tract anomalies. Thus, the
      clinical significance of many pyelectasis detected before birth is not known.
      PATIENTS AND METHODS: From a retrospective study of 78 patients, we determined
      the positive predictive value (PPV) of prenatal ultrasound findings for urinary
      tract malformations. RESULTS: This PPV was 27.3% when the prenatal pelvic
      dilatation was isolated, but grew up to 100% if a caliceal dilatation was
      associated. Renal pelvic diameter in the third trimester of pregnancy could
      predict the degree of post-natal renal impairment, as pelvic size was 6.7 +/-
      2.15 mm for the post-natal pyelectasis group, significatively smaller than 13.4
      +/- 3 mm in the ureteropelvic junction obstruction group (grade 1) and than 17 +/
      9 mm in other pathological renal units. On the other hand, antenatal ultrasound
      had a bad sensibility for vesico-ureteral reflux detection, four primary reflux
      among 14 being detected without homolateral antenatal ultrasound anomaly.
      CONCLUSION: According these results, we propose a post-natal diagnostic strategy.
      Urological explorations are performed when the prenatal renal pelvic diameter is
      larger than 10 mm. If the postnatal ultrasound shows an isolated pyelectasis
      below this level, a clinical follow-up is advised, the parents being informed of
      the possibility of vesico-ureteral reflux and of the necessity to perform a
      cytobacteriological exam of urines in case of unexplained fever.

PMID- 9230989
TI  - [Adnexal torsion in children: plea for early laparoscopic diagnosis and
      treatment].
AB  - BACKGROUND: Experience with adnexa torsion in children, a rare but potentially
      severe pathology, is still disappointing despite constant radiological progress.
      PATIENTS AND METHODS: The files of 19 patients with adnexial torsion treated
      between 1985 and 1995 were retrospectively reviewed and compared to those
      reported. RESULTS: Eight adnexectomies, six oophorectomies, five detorsions with
      cystectomy and one salpingectomy were performed. There were only five salvaged
      adnexa in this series. Three tumors were found; all other cases, except three,
      were torsions induced by voluminous functional cysts. DISCUSSION AND CONCLUSION:
      Clinical context (sudden right pelvic pain without fever) seems important to
      note. Sonographic examination is first necessary, but its results are not
      accurate enough to confirm the torsion. Endo-rectal ultrasonography should become
      the best diagnostic method in cases of complicated ovaries. In order to increase
      the percentage of salvaged adnexa, the authors recommend a laparoscopic approach
      in emergency when clinical examination was doubtful.

PMID- 9230990
TI  - [Septic sacroiliac arthritis in an adolescent].
AB  - BACKGROUND: Septic sacroiliitis is often difficult to diagnose because the
      clinical findings can be misleading and the radiological signs delayed. CASE
      REPORT: A 16-year-old adolescent was hospitalized with a history of fever and
      painful hip. The initial hypothesis of hip osteoarthritis was not confirmed by
      ultrasonography or CT-scan. The bone scan was also normal. The definitive
      diagnosis of sacroiliitis was made 1 week later based on the clinical evolution
      and a positive blood culture. It was confirmed by a second bone scan and MR
      imaging. CONCLUSION: Examination of the sacroiliac joint needs several different
      tests. Although the initial bone scan may be normal, an osteoarticular infection
      cannot be definitively ruled out and iterative radiological investigation is
      warranted. MR imaging may be an additional diagnostic tool for detecting
      sacroiliitis.

PMID- 9230991
TI  - [Angiostrongylosis in infants in Reunion and Mayotte. Apropos of 3 cases of
      eosinophilic meningitis including 1 fatal radiculo-myeloencephalitis with
      hydrocephalus].
AB  - BACKGROUND: Eosinophilic meningitis caused by Angiostrongylus cantonensis is
      widespread in Southeast Asia and Pacific islands. Adults develop a transient
      meningitis with a benign course but severe or fatal disease may occur in
      pediatric patients. CASE REPORT: Case 1. A 11-month-old boy living in Mayotte
      island was hospitalized a few days with fever and skin rash following by seizure,
      coma, flaccid quadraplegia, absence of deep tendon reflexes, urinary retention
      and anal incontinence. Eosinophilia was observed in peripheral blood and
      cerebrospinal fluid. He further developed a triventricular hydrocephalus treated
      by ventriculoperitoneal shunt. The child died 3 weeks later. A serodiagnosis of
      angiostrongylus infestation was restrospectively established. Case reports 2 and
      3.-Two infants, 10 and 11-month-old-boys, living in Reunion island, developed
      fever and vomitings, irritability and, for one of them, unilateral sixth cranial
      nerve palsy. There was eosinophilia in the peripheral blood and in the
      cerebrospinal fluid. All symptoms progressively disappeared with complete
      recovery. The suspected diagnosis of angiostrongylus infestation was confirmed by
      the serology. CONCLUSION: We report the first case of Angiostrongylus cantonensis
      infection in the French island of Mayone (Comoro Islands) and we confirm the
      presence of this disease in Reunion island. In this Indian Ocean area,
      eosinophilic meningitis occurs most of the time in infants with sometimes severe
      radiculomyeloencephalitic forms.

PMID- 9230992
TI  - [Severe streptococcal complications in varicella].
AB  - BACKGROUND: An increase in the incidence of group A beta hemolytic streptococcal
      (GABHS) infections in children has been recently noted with a frequent
      association with varicella. CASE REPORTS: Two children, 3 and 4.5 years old,
      developed varicella. The first one was febrile and presented a phlyctene on his
      left foot. Few hours after his admission, he presented a septic shock; GABHS was
      isolated from blood. Despite immediate adapted antibiotherapy, he developed a
      right tibial osteomyelitis with abscess. The second child also developed
      varicella and was hospitalized because of fever, bad general condition, right
      cervical adenitis and edema on the left wrist. Edema rapidly extended to the hand
      and upper arm. One purulent lesion was noted on the upper arm from whom
      Staphylococcus aureus and GABHS were isolated. Blood samples were sterile. The
      clinical course was favorable with adapted antibiotherapy. A cutaneous
      desquamation was observed on the 9th day and we concluded that it was a GABHS
      cellulitis. CONCLUSION: These two cases confirm the recent report of increase in
      GABHS infections associated with varicella. Such complications must be looked for
      in patients with varicella remaining abnormally febrile and/or presenting unusual
      manifestations.

PMID- 9230993
TI  - [Primary hypothyroidism revealing pseudohypoparathyroidism without hypocalcemia
      and hyperphosphoremia].
AB  - BACKGROUND: Type la pseudohypoparathyroidism is due to a molecular defect causing
      Gs protein deficiency. It is responsible for multi-hormonal resistance and
      skeletal abnormalities. Parathyroid hormone resistance can be subtle so that the
      diagnosis can be difficult in patients with atypical manifestations. CASE REPORT:
      A 10-year-old boy was first referred for growth retardation (height standard
      deviation score: -2.8). He had short metacarpals, and scaphocephaly. Laboratory
      findings revealed an elevation of plasma TSH (8,8 microU/mL) with normal thyroid
      hormone levels. The investigations ruled out common causes of compensated
      hypothyroidism. Despite normal blood calcium and phosphate levels, parathyroid
      hormone was elevated to 358 pg/mL (normal values: 10-60) without renal failure,
      suggestive of hormonal resistance. The diagnosis of pseudohypoparathyroidism type
      la was confirmed by a 50% reduction of Gs activity. Melanodermia, associated with
      an elevation of ACTH was suggestive of ACTH resistance without MSH resistance.
      Moreover, skeletal radiography showed a narrow lumbar canal. CONCLUSION: Type la
      pseudoypoparathyroidism could be part of the etiological diagnosis of primary
      hypothyroidism, even in the absence of hypocalcemia and hyperphosphatemia.
      Similarly, skeletal abnormalities extend beyond the classical features of
      Albright's osteodystrophy.

PMID- 9230994
TI  - [Smith-Magenis syndrome].
AB  - BACKGROUND: The main features of the Smith-Magenis syndrome include broad flat
      midface, brachycephaly, broad nasal bridge, brachydactyly, hoarse deep voice,
      speech and developmental delay, and behavioral anomalies. This syndrome is due to
      interstitial deletion of chromosome 17p11.2. CASE REPORT: A 7-year-old girl was
      admitted for mental retardation. Clinical examination showed brachycephaly, broad
      flat midface, broad nasal bridge, malar hypoplasia, brachydactyly, decreased or
      absent deep tendon reflexes, and hoarse deep voice. She had a mild deafness,
      behavioral problems, and sleep disturbances. Chromosome analysis on lymphocytes
      identified a microdeletion of one chromosome subband 17p11.2. Molecular studies
      indicated loss of maternal allele. CONCLUSION: The Smith-Magenis syndrome is
      probably underdiagnosed because of its usually mild clinical features. High
      resolution chromosome analysis is needed for diagnosis.

PMID- 9230995
TI  - [Severe trauma in children].
AB  - Trauma are responsible for approximately 50% of the deaths of the pediatric
      population between 1-15 years of age. This high mortality rate, associated with
      frequent sequelae, leading sometimes to severe handicaps, is a major problem of
      public health in the developed countries. Pediatric trauma have some
      particularities, due to anatomical and physiological differences, and to specific
      injury mechanisms. Management of a patient with severe trauma is best performed
      by trained physicians, working in a multidisciplinary team with a two steps
      approach: 1) emergency rapid clinical assessment and resuscitation. 2) a
      secondary complete clinical evaluation associated with medical imaging, mainly
      based on CT scan. Head injuries are frequent and represent the main prognosis
      factor, mass lesions being less frequent and cerebral oedema more frequent in
      children, than in adult; brain swelling appears to be less frequent than
      initially reported. Management of head trauma has evolved in recent years, and is
      now largely directed towards the prevention of secondary ischemic brain injury:
      new monitoring devices are proposed to pursue that goal: transcranial doppler and
      continuous jugular vein oxygen saturation monitoring. Spinal cord injuries are
      rare but may be severe: cervical and spinal cord injuries without radiological
      abnormality (SC/WORA) appear to be more frequent than in adult. Most often,
      abdominal plain viscera injuries are treated with a conservative non operative
      approach. Among chest injuries, pulmonary contusion is the most frequent, with a
      favorable outcome in most cases within 3-4 days. Child abuse must be suspected in
      any case where there is no clear injury mechanism or when there is a discrepancy
      between the severity of the injury and the alleged mechanism.

PMID- 9230996
TI  - [Treatment of infectious osteoarthritis in children].
AB  - Treatment of septic arthritis is an emergency; therefore antibiotherapy must be
      started rapidly following the bacteriological sampling. The risk for the articles
      justifies that treatment be started with two antibiotics given intravenously, the
      choice of the antibiotics being dependent upon the clinical history. If the
      bacteria is isolated, an adopted monotherapy is then maintained. A drainage of
      the joint can be performed by needle aspiration or by a percutaneous catheter,
      and in case of difficulty to control the sepsis, by surgical debridment.
      Intravenous antibiotherapy is maintained for 7 to 15 days. Whenever a good
      response is observed the treatment is continued orally for a total duration of 4
      to 6 weeks.

PMID- 9230997
TI  - [Orthopedic treatment of scoliosis: new technique using impression by optic
      procedure].
AB  - The authors present a new procedure for acquiring the whole external trunk shape.
      The construction of braces starts with corrected a positive mold using computer
      assisted design software connected to a digital tooling machine. The computer
      assisted design and construction of braces enable the determination, measurement,
      and modification of a three-dimensional image of the trunk, which allows the
      positive to be corrected. The outer-trunk can be re-balanced, derotated or
      rectified in the sagittal or frontal plane and the inner modeling of the spine
      and chest can be rectified. Moreover, in the case of scoliosis or kyphosis, the
      software produces automatic correction. This rapid (acquisition time < 2
      seconds), non invasive, safe and painless procedure can also be used to detect
      and follow mild spinal deformities.

PMID- 9230998
TI  - [Apropos of families where parents are battered by their children].
AB  - Although the reported prevalence rate of children who assault their parents is
      high, ranging from 0.6 to 16%, publications dealing with this subject are rare.
      Based upon data from the literature and a personal experience the family
      structure of such aggressive parents-children relationships are described in an
      attempt to define causative mechanisms. This may help to early recognition and
      prevention of this type of familial violence.

PMID- 9231000
TI  - [Radiological case of the month. Aneurysmal malformation of the vein of Galen].

PMID- 9230999
TI  - [Protection of the thyroid in children and fetuses in case of nuclear accident].
AB  - The administration of stable iodine in order to keep the thyroid gland away from
      radioactive iodine isotope contamination has long been regarded with caution by
      the health authorities, mainly because of the potential toxicity of iodine in
      newborns, young children and adults with thyroid pathology. Therefore, the risk
      of oral stable iodine given for a limited period of time must be compared to the
      risk of cancer due to radioactive exposure. The analysis of complications
      following the nuclear accidents of Marshall Islands in 1954 and Tchernobyl in
      1986 has shown that newborn infants and young children, have the highest risk,
      the main complications being cancer (papillary carcinoma) and hypothyroidism. In
      the most exposed areas of Bielorussia, the incidence of child thyroid cancer has
      been approximately multiplied by 100. On the other hand, studies of children from
      Utah who were contaminated after nuclear tests in the Nevada desert have shown
      that following mild iodine radioactive exposure, the risk is not significant.
      Among complications attributed to stable iodine, only those related to an oral
      intake over a limited period of time should be considered. On the basis of
      nuclear medicine experience and scientific literature, the risk can be considered
      as negligible in adults but not in children. However, the Polish experience in
      children has reported a low risk and only benign complications, mainly transient
      hypothyroidism. Thus from current knowledge, it appears that the potent risks
      linked to stable iodine administration should not contraindicate the collective
      preventive stable iodine administration in case of nuclear accident.

PMID- 9231001
TI  - [Necrosis of the nasal columella secondary to nasal continuous positive airway
      pressure].

PMID- 9231002
TI  - [Discharge of premature infants: benefits and contraindications].

PMID- 9231003
TI  - [Incidence of rheumatoid purpura in children and frequency of associated
      nephropathy in the Loire region].

PMID- 9231004
TI  - Cerebrospinal fluid rhinorrhoea.

PMID- 9231005
TI  - The effect of changes in barometric pressure on the risk of rupture of
      intracranial aneurysms.
AB  - Several meteorological variables have been linked with an altered incidence of
      cerebrovascular disease. In particular, we had noticed that, following abrupt
      changes in weather, patients with aneurysmal subarachnoid haemorrhage (SAH) often
      presented in groups. This study was undertaken to determine whether changes in
      barometric pressure would be an important factor. A retrospective analysis of a
      two year period was carried out. Daily mean, peak and trough atmospheric
      pressures had been recorded independently by a weather bureau. Of the 157
      patients with SAH due to a berry aneurysm, confirmed by CT and angiography, 60
      were entered into the study. Patients residing outside the weather bureau region
      (n = 86), or where there was uncertainty of their day of ictus (n = 11), were
      excluded. Daily peak to trough pressure changes and mean monthly pressure
      fluctuations showed no association with an increased risk of SAH. However, a
      significant relationship between the incidence of onset of symptoms indicative of
      a rupture of the aneurysm and a change in barometric mean pressure (BMP) of > 10
      hectapascals from the previous day was found (p = 0.0247). The calculated odds
      ratio of sustaining a SAH with this associated BMP change was therefore 2.7 times
      with a risk of 1-13 times at a 95% confidence level (p = 0.035).

PMID- 9231007
TI  - Intrinsic brainstem tumours in childhood: a report of 35 children followed for a
      minimum of 5 years.
AB  - The presentation, pathology and outcome of 35 children with intrinsic brainstem
      tumours treated at our institution between 1980 and 1990 have been reviewed.
      Eight children remain alive. There were 19 girls and 16 boys. Mean age at
      diagnosis was 5 years. The mean duration of symptoms prior to diagnosis was 5
      months. The diagnosis was made by computed tomography (CT) in all children and
      magnetic resonance imaging (MRI), in addition, for 24 children. Twenty-seven
      tumours (77%) were diffuse, three (8.6%) were predominantly cystic, three (8.6%)
      were exophytic and two (5.7%) were focal. Cervicomedullary tumours were not
      included in this study. Definitive histology was obtained in 13 children (37.1%),
      eight (22.9%) by biopsy alone and five (14.3%) after surgery to debulk the
      tumours. Eleven of these cases were astrocytomas and two were primitive
      neuroectodermal tumours (PNET). Twelve children (34.3%) required shunt placement
      for hydrocephalus. Twenty-eight children (80%) were irradiated using
      conventionally fractionated radiotherapy to a total dose between 50 and 55 Gy.
      Six children (17.1%) also received chemotherapy. The overall mean survival time
      was 10 months, but five of six children who had their tumours debulked survived
      free of progressive disease for more than 5 years following their diagnosis. The
      prognosis for brainstem tumours in children remains poor with only a minority
      falling into the surgically resectable (good prognosis) group.

PMID- 9231006
TI  - Effects of photodynamic therapy on glioma spheroids.
AB  - The present study describes the sensitivity of glioma cells to a haematoporphyrin
      derivative (Photosan-3) under laser activation (argon-pumped dye laser). The
      effects of photodynamic therapy (PDT) on cell growth, directional migration and
      cell invasion were investigated on two human glioma cell lines (GaMg and U-251
      Mg). The directional cell migration and spheroid growth was determined for both
      cell lines exposed to increasing laser energy output (15-35J/cm2) with
      concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a
      dose-dependent migratory response to increasing laser irradiation, that was more
      prominent in the 7 micrograms/ml treatment group. This effect occurred during the
      first 4 days after drug exposure. Also, spheroids from both cell lines showed a
      drug and laser output energy dose-dependent inhibition of growth which became
      apparent after a lag period of 6 days. The lag period was characterized by a
      decreased growth rate as compared with the control group. During this period the
      outer cell layers of the spheroids fell apart. The remaining spheroid tissue was
      not able to migrate and to regrow when exposed to the highest laser energy
      outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed,
      however, the ability for invasion when confronted with normal brain cell
      aggregated in vivo. Light microscopic observations of co-cultures between tumour
      tissue and brain cell aggregates revealed a normal tumour morphology. This
      indicates that the remaining tumour cells were not dead and could be stimulated
      to invade the normal tissue when exposed to a normal brain microenvironment.

PMID- 9231008
TI  - Prognostic factors in delayed ischaemic deficit with vasospasm in patients
      undergoing early aneurysm surgery.
AB  - We have examined prognostic factors in delayed ischaemic deficit attributed to
      vasospasm following subarachnoid haemorrhage (SAH) and early aneurysm surgery.
      Among 605 patients with SAH, 201 patients developed a delayed ischaemic deficit
      and 137 of these underwent early surgery. These 137 patients were classified into
      groups A and B by outcome at 3 months after SAH (group A: the delayed ischaemic
      deficit was associated with an adverse outcome; group B: no adverse outcome).
      Factors indicating an unfavourable outcome were as follows: (i) older age; (ii)
      poor WFNS grade on admission; (iii) Fisher's scale of 4; (iv) intracerebral
      haemorrhage; (v) delayed ischaemic deficit following rerupture; (vi)
      complications of surgical intervention; (vii) delayed ischaemic deficit with
      disturbance of consciousness; (viii) lack of immediate improvement with
      hypervolaemic therapy; and (ix) intracranial complications after hypervolaemic
      therapy. We suggest that the reversibility of a delayed ischaemic deficit is
      determined by preceding brain damage and/or surgical complications.

PMID- 9231009
TI  - Increased levels of cholesterol esters in glioma tissue and surrounding areas of
      human brain.
AB  - The proliferation of glioma cells requires cholesterol, which could be provided
      by synthesis within the cells or by uptake of cholesterol esters in particles of
      Low Density Lipoprotein (LDL). Cholesterol esters and cholesterol were therefore
      analysed in human glioma tissue, its surrounding areas and serum from 40
      patients. The analyses revealed an increased concentration of cholesterol esters
      up to 100 times (0.1-10 mumol/g) in both tumour-tissue and surrounding areas
      compared with control material (< 0.1 mumol/g). The analyses also demonstrated
      that cholesterol esters in tumour tissue eminated mainly from serum. The
      cholesterol concentrations were significantly lower in tumour tissue compared
      with surrounding areas as expected. These results indicate that tumour cell
      proliferation utilises serum derived cholesterol esters presumably carried by LDL
      particles.

PMID- 9231010
TI  - Preliminary experience of carbon fibre cage prostheses for treatment of cervical
      spine disorders.
AB  - The objective of this study was to assess the technical feasibility, and the
      clinical and radiological results of interbody fusion with a carbon fibre cage
      following anterior cervical discectomy. Nineteen consecutive patients, eight male
      and 11 female, with an age range from 28 to 75 years (mean 45) underwent anterior
      cervical discectomy and interbody fusion with a carbon fibre cage at one or two
      levels. Subjective assessment of symptomatic improvement and radiological
      assessment of cervical spine alignment and stability was made. All complications
      were recorded. The procedure was technically feasible. There was no increased
      morbidity and the length of procedure was no longer when compared with the
      similar operation but using tricorticate bone graft. All patients initially lost
      their radicular symptoms and the patients with myelopathy had subjective
      improvements of their symptoms. Fourteen of the 17 patients with neck pain showed
      some improvement. Bony fusion was achieved in all cases.

PMID- 9231011
TI  - Spinal intradural extramedullary cavernous angiomas: report of four cases and
      review of the literature.
AB  - Spinal cavernous haemangiomas are rare and an intradural extramedullary location
      is rarer still. We give a detailed report of four such cases with a review of 12
      cases reported in the past. The clinical presentation, investigations and
      treatment are discussed.

PMID- 9231012
TI  - Arterial and venous paragangliomas: the value of a preoperative pacemaker and a
      multidisciplinary approach.
AB  - Non-chromaffin paragangliomas are very rare tumours. They arise from
      chemoreceptor cells at multiple sites throughout the body. They are usually very
      vascular and most arise in intimate contact with vital structures making their
      excision a surgical challenge. We describe in this paper four cases of
      paragangliomas in the carotid body and the jugular bulb. Their presentation was
      unusual. Two cases underwent excisional surgery and two had radiation treatment
      because they were not fit for surgery. We had to use a temporary pacemaker for
      preoperative preparation of the carotid body because of an associated
      hypersensitive carotid sinus syndrome. The clinical presentation and the surgical
      management will be described in this paper.

PMID- 9231013
TI  - Dorsal root entry zone lesion performed with Nd:YAG laser.
AB  - Thermocoagulation of the dorsal root entry zone (DREZ) is the current surgical
      management of deafferentation pain syndromes. It is usually performed with the
      assistance of specially designed lesion generators. We report a patient who
      underwent a DREZ lesion with a Nd:YAG laser as an alternative to standard
      thermocoagulation technique. A 62-year-old woman with a 5-year history of
      bilateral dysaesthetic (burning) type of leg pain, after a crush fracture of the
      fourth thoracic vertebra and complete cord transection, was managed by inducing a
      bilateral dorsal root entry zone lesion at T2-T5 myelotomes using a Nd:YAG laser,
      which was used as an alternative to the conventional electrically generated
      thermocoagulation. A significant reduction of deafferentation type of pain was
      achieved.

PMID- 9231014
TI  - Neuroblastoma and venous sinus thrombosis in an adult patient.
AB  - A 35-year-old woman developed symptoms consistent with intracranial venous sinus
      occlusions that were demonstrated by MR angiography. After a few weeks of
      anticoagulant therapy, she became paraplegic due to haemorrhages in the caudal
      spinal canal. A decompressive laminectomy did not improve her neurological
      deficits. Up to this point, we assumed her condition to be caused solely by the
      intracranial venous thrombosis and complications of the treatment. A tumour
      diagnosis had so far not been considered. A few months later she became
      tetraplegic. MRI revealed fresh bleeding in the upper spinal cord and a
      dissemination of tumour along the entire craniospinal axis. Biopsy specimens
      obtained from the spinal canal contained tumour cells with the characteristics of
      neuroblastoma.

PMID- 9231015
TI  - Transoral evacuation of a clivus extradural haematoma with good recovery: a case
      report.
AB  - We report a case of traumatic atlanto-axial dislocation with a clivus and upper
      cervical extradural haematoma causing tetraplegia and respiratory paralysis.
      Surgical evacuation via the transoral route with posterior atlanto-axial fixation
      resulted in survival with a good outcome.

PMID- 9231016
TI  - Multiple primary cerebral hydatid cysts: case report.
AB  - The authors report the case of a patient with primary multiple cerebral hydatid
      cysts emphasizing the role played by MRI in planning the surgical approach. The
      indications for medical treatment of such lesions are also discussed.

PMID- 9231017
TI  - Intracerebral osteoma: case report.
AB  - A 28-year-old woman presented with 6 months of intractable left frontal headache
      that was proved to be due to an intracranial lesion. After successful surgical
      removal, it was found to be an intracerebral osteoma without a dural attachment.
      The literature of intracerebral osteoma is reviewed.

PMID- 9231018
TI  - Pneumocephalus associated with fracture of thoracic spine: case report.
AB  - A 53-year-old man presented with pneumocephalus following a thoracic vertebral
      fracture. Computed tomography (CT) myelography revealed a leakage of contrast
      medium from the thecal sac in the vicinity of the vertebral fracture and was used
      to confirm the origin of a subarachnoid-pleural fistula.

PMID- 9231019
TI  - Granular cell tumour of the spinal cord in a patient with Rubenstein-Taybi
      syndrome.
AB  - A case of cervical spinal cord granular cell tumour in a patient with Rubenstein
      Taybi syndrome is described. A granular cell tumour arising from the spinal cord
      itself has never been previously described. Complete excision of the tumour could
      not be achieved owing to its location. It subsequently recurred and was treated
      with radiotherapy. The patient made a complete recovery with no further
      recurrence after 2 years of follow-up.

PMID- 9231020
TI  - Delayed aneurysm formation following surgery for a giant serpentine aneurysm.
AB  - We report a case of a giant serpentine aneurysm of the right middle cerebral
      artery (MCA) that was treated by total excision of the aneurysm with cerebral
      blood flow control management. Four years later the patient presented with a
      three month history of headache and angiograms showed a new aneurysm on a
      different branch of the MCA which is thought to have been caused by the previous
      surgical dissection.

PMID- 9231021
TI  - Intradural tuberculous granuloma.

PMID- 9231022
TI  - Glomus tumours of the skull base.

PMID- 9231024
TI  - A lesson--a biter bit?

PMID- 9231023
TI  - Multicystic lesions of the brainstem. Reply to Dr Poirier.

PMID- 9231025
TI  - Be still my beating heart.

PMID- 9231026
TI  - Compensated cardiac hypertrophy: arrhythmogenicity and the new myocardial
      phenotype. I. Fibrosis.
AB  - The high incidence of arrhythmias in compensated cardiac hypertrophy is related
      to two independently regulated components-fibrosis and the adaptational
      phenotypic changes in membrane proteins linked to cardiac hypertrophy, and
      fibrosis. During the regression of hypertensive cardiopathy in middle-aged
      spontaneously hypertensive rats, the roles of cardiac hypertrophy and fibrosis
      can be analysed separately, revealing that both correlate independently with
      arrhythmias. In an experimental model of myocardial infarction it is possible to
      prevent arrhythmias with propranolol at the same time as cardiac hypertrophy,
      despite ventricular fibrosis. Fibrosis would appear to create arrhythmias both by
      anatomical uncoupling and by a re-entry mechanism generated by the zig-zag
      propagation of the transverse waveform. Triggered activity and automaticity
      depend on the membrane phenotype of the cardiocyte. They also play an important
      role, which is aggravated by myocardial heterogeneity.

PMID- 9231027
TI  - Reactive oxygen metabolites and arterial thrombosis.
AB  - Arterial thrombus formation is the result of complex events which require the
      interaction of damaged vessel walls with blood cellular elements and coagulation
      factors, and in which several mediators may play a role. In this context, the
      role of 'classical' chemical mediators such as thrombin, thromboxane or serotonin
      in initiating and/or amplifying intravascular thrombus formation is well
      established. However, it is now being recognized that certain chemical species
      formed in the metabolism of oxygen may also be involved in the process of
      arterial thrombosis. This review will focus on recent evidence in this field.

PMID- 9231028
TI  - Role of interventricular dispersion of repolarization in acquired torsade-de
      pointes arrhythmias: reversal by magnesium.
AB  - OBJECTIVE: The mechanism of acquired torsade-de-pointes arrhythmias (TdP) is not
      clear but is suggested to be based on several parameters including early
      afterdepolarizations (EADs) and/or dispersion of repolarization (delta APD). In
      our animal model of TdP (anaesthetized dogs with chronic AV block), we assessed
      the relevance of interventricular dispersion for the initiation of TdP. METHODS:
      In 24 experiments, multiple endocardial monophasic action potential (MAP)
      recordings were made at baseline, after d-sotalol (2 mg/kg), and after MgSO4 (100
      mg/kg, n = 11) to measure regional differences in action potential duration
      (APD). Rate-dependent behavior of the interventricular delta APD (APD of left
      minus right ventricle) and intraventricular dispersion was studied under the
      different circumstances. RESULTS: Dogs with induction of TdP by d-sotalol and
      pacing (11/20 = 55%) had longer cycle lengths of idioventricular rhythm, longer
      QT-durations, increased presence of EADs (14/22 vs 5/18 MAPs, P < 0.05) and
      increased interventricular delta APD (135 +/- 55 vs 60 +/- 40 ms. P < 0.05)
      compared with non-inducible dogs. There were no differences in intraventricular
      dispersion. MgSO4 diminished delta APD (110 +/- 45 to 55 +/- 60 ms, P < 0.05) and
      prevented TdP (4/4). In contrast to intraventricular dispersion, interventricular
      delta APD is clearly bradycardia-dependent. CONCLUSIONS: Next to bradycardia,
      prolonged repolarization, and EADs, we propose that delta APD should be added to
      the relevant factors for the initiation of TdP. Interventricular dispersion is
      much larger than intraventricular dispersion and demonstrates a very strong
      bradycardia dependence.

PMID- 9231029
TI  - Effects of renin inhibition compared to angiotensin converting enzyme inhibition
      in conscious dogs with pacing-induced heart failure.
AB  - OBJECTIVE: To compare the effects of angiotensin converting enzyme inhibition
      (ACEI) (captopril 1 mg/kg i.v.) to direct renin inhibition (CP80794 3 mg/kg i.v.)
      on left ventricular and systemic hemodynamics and peripheral blood flows in
      advanced congestive heart failure (CHF). METHODS: Conscious chronically
      instrumented dogs (n = 14) were treated with captopril, 1 mg/kg, i.v., or
      CP80794, 3 mg/kg, i.v., before and after development of advanced CHF induced by 4
      7 weeks of rapid ventricular pacing. After advanced CHF, comparisons between the
      inhibitors were made at equihypotensive doses. RESULTS: In advanced CHF, both
      agents caused comparable reductions in mean arterial pressure (MAP) (-22% from 79
      +/- 4 mmHg) and comparable increases (P < 0.01) in cardiac output (CP80794, 1.4
      +/- 0.3 to 1.8 +/- 0.1 l/min; captopril, 1.4 +/- 0.1 to 1.9 +/- 0.1 l/min).
      Neither agent had a significant effect on LV contractility. In contrast, CP80794
      caused a greater (P < 0.05) increase in renal blood flow (66 +/- 6% from 64 +/- 5
      ml/min) compared to captopril (33 +/- 4% from 66 +/- 7 ml/min). CONCLUSIONS:
      Renin inhibition with CP80794 and ACEI with captopril caused comparable
      hemodynamic effects in advanced CHF. However, CP80794 caused significantly
      greater increases in renal blood flow and suppressed renin activity to a greater
      degree than captopril.

PMID- 9231030
TI  - Cardiac depression after experimental air embolism in pigs: role of addition of a
      surface-active agent.
AB  - OBJECTIVE: Air bubbles entering the coronary artery may have harmful effects on
      cardiac function. From the physical point of view it is the relatively high
      surface tension of the blood-air interface which causes bubbles to trap in small
      vessels. The aim of the present study was to reduce depression of myocardial
      function from air embolism by lowering the surface tension of air bubbles.
      METHODS: The effect of using antifoam as a surface-tension-reducing agent on air
      bubble entrapment and cardiac function was investigated in 6 anesthetized pigs
      (27 +/- 1 kg) and analyzed using a two-compartment diffusion model. Air bubbles
      with a diameter of 150 microns were selectively injected into the left anterior
      descending coronary artery (LADCA) in a carrying fluid in the presence or absence
      of antifoam. Myocardial systolic segment shortening in the LADCA region (SS
      LADCA) was measured by sonomicrometry. Presence of emboli was detected by
      measuring the amount of reverberation of ultrasound scattered by trapped air
      bubbles. RESULTS: SS-LADCA transiently decreased after injections of air bubbles
      in both the absence and presence of antifoam. However, in the presence of
      antifoam the regional depression recovered to normal sooner, the average depth of
      the depression was reduced, and bubbles from the embolized area cleared faster.
      These observations can be explained by a model derived from Laplace's law.

PMID- 9231031
TI  - Age dependence of the development of ventricular arrhythmias in a canine model of
      sudden cardiac death.
AB  - OBJECTIVES: The age-dependence of the development of ventricular arrhythmias was
      studied in German shepherd dogs with inherited ventricular arrhythmias and sudden
      death. BACKGROUND: A colony of German shepherd dogs has been established that
      exhibit inherited ventricular arrhythmias and sudden death. The incidence of
      arrhythmias increases with age. Because ventricular tachycardia is associated
      with bradycardia, it was hypothesized that the increased incidence of arrhythmias
      was related to age-dependent slowing of heart rate. METHODS: Arrhythmia counts
      and RR intervals were measured from serial ambulatory ECG recordings obtained in
      71 dogs (1-48 weeks). In addition, 19 dogs were challenged with phenylephrine (10
      micrograms/kg i.v.) at 15, 28, and 45 weeks of age, 10 dogs were challenged with
      epinephrine (1 microgram/kg i.v.) at 3, 5, 7, 9, 11, 18, and 28 weeks of age, and
      10 dogs were challenged at 28 weeks with epinephrine (2.5 micrograms/kg i.v.),
      before and after propranolol (0.5 mg/kg i.v.). RESULTS: The incidence and
      severity of ventricular arrhythmias increased between 7 and 28 weeks of age and
      decreased between 28 and 44 weeks of age. The age-dependent increase in the
      incidence of ventricular tachycardia was associated with age-dependent reductions
      in sinus rate. Baroreflex-mediated slowing of the heart rate unmasked arrhythmias
      in young animals that did not spontaneously display arrthythmias and exacerbated
      existing arrhythmias in older animals. However, the magnitude of baroreflex
      induced bradycardia was similar from 7-18 weeks of age, yet the incidence of
      arrhythmias increased progressively. Moreover, the waning of ventricular
      arrhythmias in older animals was not associated with more rapid sinus rates.
      CONCLUSION: The risk for sudden death in dogs with inherited ventricular
      arrhythmias increases with age in part because of age-dependent slowing of heart
      rate and in part because of other heart-rate-independent factors. The
      correspondence between the development of ventricular tachycardia and sinus
      pauses is consistent with the hypothesis that ventricular arrhythmias are
      initiated by early afterdepolarization-induced triggered activity.

PMID- 9231032
TI  - Effect of streptomycin on wall-stress-induced arrhythmias in the working rat
      heart.
AB  - OBJECTIVE: To assess whether streptomycin, an inhibitor of mechano-sensitive
      cation channels, has an effect on arrhythmias-induced by an increase of
      ventricular wall stress in the rat heart. METHODS: The isolated working rat heart
      preparation was used. Arrhythmias were induced by increasing the afterload (i.e.,
      aortic pressure) against which the left ventricle (LV) pumped for 20 s. This led
      to an increase of LV pressure, stretch of the LV and an increase in LV wall
      stress. The number of ventricular premature beats induced by each afterload step
      was compared in the absence and presence of streptomycin, a compound known to
      block mechano-sensitive cation channels in the heart. RESULTS: Perfusion with 200
      microM streptomycin caused a significant reduction in wall-stress-induced
      arrhythmias. The effect of streptomycin on arrhythmias reached steady-state
      within 10 min of application. In the presence of streptomycin, arrhythmias
      elicited by a 40 mmHg afterload increase were reduced to 38% of control.
      Arrhythmias induced by an 80 mmHg afterload increase were reduced to 61% of
      control. Complex arrhythmias (ventricular tachycardia) induced by an afterload
      increase were also reduced in the presence of 200 microM streptomycin. There was
      no change in inotropic state with streptomycin, as assessed either by cardiac
      output or by maximum developed LV pressure. Streptomycin 50 microM (a typical
      therapeutic plasma concentration in patients) had no effect on wall-stress
      induced arrhythmias. CONCLUSIONS: The results were inconsistent with streptomycin
      acting by modulating inositol phosphate production, or altering the level of
      intracellular calcium or inotropic state. The anti-arrhythmic effect of
      streptomycin appears more consistent with inhibition of mechano-sensitive cation
      channels, suggesting that these ion channels might be involved in causing wall
      stress-induced arrhythmias.

PMID- 9231033
TI  - Red cell flux during the cardiac cycle in the rabbit myocardial microcirculation.
AB  - OBJECTIVE: (1) To measure regional phasic myocardial red cell flux during a
      cardiac cycle using a laser Doppler velocimeter. (2) To test the responses of
      regional red cell flux to a vasodilator (adenosine), a vasoconstrictor
      (angiotensin II), and an inotrope (isoproterenol). METHODS: Using an
      anaesthetised open-chest rabbit with the pericardium intact a 140-micron-tip
      fibre optic probe was placed in the left ventricular myocardium in various
      locations. With the fibre in place drugs were given to alter myocardial loading
      conditions while red cell flux was registered. RESULTS: Phasic red cell flux was
      similar in the epicardium to endocardium giving an average endo/epi ratio of 1.14
      in the rabbit heart. At least two peaks of increased red cell flux within a
      single cardiac cycle were observed. Some unique patterns for red cell flux were
      observed in specialised myocardial structures. Adenosine increased red cell flux
      but minimally changed the pattern of phasic flux throughout the cycle.
      CONCLUSIONS: Laser Doppler velocimetry permits the recording of phasic red cell
      flux during the cardiac cycle in the myocardial microcirculation. Its pattern is
      determined by both coronary arterial inflow and venous outflow. The pattern of
      red cell flux may be characteristic for a region-probably determined by
      difference in tissue pressure (attributable to the pattern of muscle fibre
      shortening and collagen tethering) and changes in capillary length and density.

PMID- 9231034
TI  - Cardiac morphology at late fetal stages in the mouse with trisomy 16:
      consequences for different formation of the atrioventricular junction when
      compared to humans with trisomy 21.
AB  - OBJECTIVE: The mouse with trisomy 16 (Ts16) is held to be a genetic model for
      humans with Down's syndrome (Ts21). Both trisomies are associated with
      atrioventricular septal defects, but the precise morphology in the mouse remains
      unclear. We have therefore characterised cardiac morphology in the mouse with
      Ts16. METHODS: Ts16 fetuses, from a Rb(11.16)2H/Rb(16.17)7Bnr x C57BL/6J cross,
      were collected on gestational days 17 or 18 (full term = 19 days) and studied
      using scanning electron microscopy and serial sections. RESULTS: The hearts
      showed a spectrum of deficient atrioventricular septation which we categorised
      into two types. In one, a common atrioventricular junction was separated into
      right and left orifices by a tongue of tissue joining two valvar leaflets that
      bridged the ventricular septum to varying extent. In the other, a common
      atrioventricular junction was connected exclusively to the left ventricle. All
      hearts had ostium primum atrial and ventricular septal defects, together with
      abnormal ventriculo-arterial connections. No heart had the typical morphology
      seen in the human with Down's syndrome, namely a balanced common atrioventricular
      junction, guarded by a common valve, with the aorta connected exclusively to the
      left ventricle. CONCLUSIONS: The cardiac defects seen in Ts16 mice show marked
      differences from the typical anatomy in human Ts21, suggesting more complex
      mechanisms of cardiac dysmorphogenesis in Ts16. The mouse model will prove
      valuable in elucidating the mechanism of normal expansion of the atrioventricular
      junctions, and help in charting the precise steps involved in atrial and
      ventricular septation.

PMID- 9231035
TI  - Cardiac output distribution in the chick embryo from stage 36 to 45.
AB  - OBJECTIVE: The distribution of cardiac output to different organs is well
      described in the mammalian fetus. Chick embryos are not often used in perinatal
      cardiovascular research and therefore it is not known whether they can serve as
      an animal model for this purpose. In this study we documented cardiac output
      distribution in chick embryos at increasing incubation time. METHODS: Fertilized
      eggs from day 10 to 19 with an incubation time of 21 days were studied in 3
      increasing incubation time groups (10-13, 14-16 and 17-19 days). For the
      experiment, the egg was placed in a holder in an incubator. The egg was opened at
      the air cell and a small vein of the chorioallantoic membrane was catheterized.
      Twenty thousand fluorescent 15 microns microspheres in 0.2 ml were injected.
      After 5 min, the embryo was sacrificed and the different organs were dissected
      and digested for microsphere isolation and subsequent fluorescence analysis.
      RESULTS: The chorioallantoic membrane, which is the placenta equivalent of the
      chick embryo, received a relatively large fraction of the combined cardiac
      output: 52.08% (interquartile range [IQR] 12.67%) on days 10-13 and 40.95% (IQR
      27.24%) on days 17-19. Relatively small fractions were distributed: to the heart
      2.03% (IQR 1.58) on days 10-13 and 3.18% (IQR 1.95) on days 17-19, and to the
      brain 3.20% (IQR 1.80) on days 10-13 and 5.02% (IQR 3.39) on days 17-19. As
      incubation time advanced, the fraction of the combined cardiac output to the
      chorioallantoic membrane and yolk-sac decreased significantly in favor of the
      heart and brain. CONCLUSION: This distribution shows great similarity to the one
      found in the mammalian fetus. The chick embryo is an attractive model for
      perinatal cardiovascular research.

PMID- 9231036
TI  - Effects of 17 beta-estradiol and progesterone on migration of human monocytic THP
      1 cells stimulated by minimally oxidized low-density lipoprotein in vitro.
AB  - OBJECTIVE: Many epidemiological studies have shown that postmenopausal hormone
      replacement therapy (HRT) has a beneficial effect on atherosclerotic
      cardiovascular disease. The aim of this study was to investigate the effects of
      estrogen and progestin on the migration of monocytes induced by minimally
      oxidized low-density lipoprotein (m-ox-LDL) in vitro. METHODS: Human monocytic
      THP-1 cells were used for the study. Migration assay was performed using a
      modified Boyden chamber. RESULTS: The presence of estrogen receptors was
      determined in THP-1 cells by Western and Northern blot analysis. Although native
      LDL had no significant effects on the migration of THP-1 cells, m-ox-LDL
      increased the migration of THP-1 cells in a dose-dependent manner. Although 17
      beta-estradiol (E2, 10(-9)-10(-6) M) inhibited the 10 micrograms/ml-induced
      migration of THP-1 cells in a dose-dependent manner, estrone (E1), estriol (E3)
      and progesterone (P) had no significant effects. The combination of P (10(-9)-10(
      6) M) did not show any effect on the inhibitory effect of 10(-7) M E2.
      Preincubation of THP-1 cells with the anti-estrogenic agent, tamoxifen (10(-6)
      M), significantly antagonized the inhibitory effect of 10(-7) M E2. m-ox-LDL
      stimulated MCP-1 secretion from THP-1 cells, which was reduced by E2. Anti-human
      MCP-1 neutralizing antibody inhibited the migration of THP-1 cells stimulated by
      m-ox-LDL. E2 also inhibited the 10 ng/ml MCP-1-induced migration of THP-1 cells
      in a dose-dependent manner. CONCLUSIONS: These findings suggest that the
      inhibitory effect of E2 on the migration of monocytes might be one of the factors
      involved in the decreased incidence of atherosclerotic cardiovascular disease in
      premenopausal women and postmenopausal HRT.

PMID- 9231037
TI  - The role of cAMP- and cGMP-dependent protein kinases in the cardiac actions of
      the new calcium sensitizer, levosimendan.
AB  - OBJECTIVE: The role of phosphodiesterase III inhibition and calcium sensitization
      in the cardiac actions of levosimendan, (R)-[[4-(1,4,5, 6-tetrahydro-4-methyl-6
      oxo-3-pyridazinyl)phenyl]hydrazono]propane dinitrile, was studied. METHODS:
      Various heart preparations were used to investigate positive inotropy,
      chromotropy, coronary flow and calcium sensitivity of contractile proteins. The
      cAMP- and cGMP-dependent protein kinases (PKA and PKG) were inhibited by KT5720
      and KT5823, respectively. Furthermore, the synthesis of cAMP was stimulated by
      forskolin and increased phosphorylation of troponin I was induced by
      isoprenaline. RESULTS: In Langendorff guinea-pig heart, levosimendan (0.01-1
      microM) and milrinone (0.1-10 microM) increased the left ventricular systolic
      peak pressure almost to the same extent. In the presence of KT5720 (1 microM)
      milrinone was devoid of positive inotropic activity. In contrast, KT5720 did not
      antagonize the inotropic effect of levosimendan at < or = 0.03 microM (-up to the
      EC50 of levosimendan). The effects of levosimendan and milrinone on heart rate
      and coronary flow were not affected by KT5720. The PKG inhibitor, KT5823 (1
      microM), on the other hand, potentiated the levosimendan-induced increase in
      coronary flow while it had no effect on the increase induced by milrinone. The
      mechanical parameters were not affected by KT5823. In the papillary muscle, the
      positive inotropic effect of milrinone but not that of levosimendan was
      potentiated by forskolin (0.1 microM). In contrast to milrinone, the positive
      inotropy by levosimendan was decreased by isoprenaline pretreatment (0.1 microM;
      3 min). In line with this, the calcium-sensitizing effect of levosimendan was
      decreased in skinned fibers prepared from isoprenaline-treated hearts.
      CONCLUSIONS: Our results indicate that the cardiac effects of levosimendan at its
      therapeutically relevant concentrations were not mediated through PKA or PKG and
      its positive inotropy is therefore most probably due to the previously reported
      troponin-C-mediated calcium sensitization of contractile proteins.

PMID- 9231038
TI  - Alteration in the control of mitochondrial respiration by outer mitochondrial
      membrane and creatine during heart preservation.
AB  - OBJECTIVE: This study aimed to evaluate the nature and extent of mitochondrial
      alterations during heart preservation. METHODS: Rat hearts, isolated after
      cardioplegia in situ, were preserved for 6 or 15 h at 4 degrees C either by
      immersion in cardioplegic solution or by low-flow perfusion (0.3 ml/min) with
      cardioplegic solution. The energy state of hearts at the end of preservation was
      determined by 31P-NMR spectroscopy and functional recovery was evaluated on
      reperfusion. Variables of mitochondrial respiration (maximal rate of respiration
      in the presence of ADP = delta Vmax, apparent Km for ADP, effect of creatine)
      were evaluated on skinned fibers and compared with those determined in controls
      and in hearts subjected to 1 hour of ischemia at 37 degrees C. RESULTS: Serious
      mitochondrial alterations were detected in fibers from 15 h immersed hearts:
      decrease of delta Vmax and of apparent Km for ADP, loss of the stimulatory effect
      of creatine, and disruption of the outer mitochondrial membrane. The extent of
      alternations was more accentuated in fibers from normothermic ischemic hearts, in
      which some damage of the inner mitochondrial membrane also occurred. In fibers
      from hearts preserved for 6 h, no significant changes in mitochondrial variables
      could be detected. When the hearts were preserved under low-flow perfusion for 15
      h, only the stimulatory effect of creatine on respiration was significantly
      decreased. The extent of the loss of the stimulatory effect of creatine
      paralleled the accumulation of inorganic phosphate (Pi) during preservation and
      the decrease in left ventricular function on reperfusion. CONCLUSIONS:
      Alterations related to the outer membrane and the intermembrane space are among
      the earliest signs of damage to mitochondrial function during heart preservation.
      These alterations could be attributed to the swelling of mitochondria under the
      effect of Pi. The determination of mitochondrial parameters in biopsy samples
      could allow a simple and rapid evaluation of energy-producing and transfer
      capacities of the myocardium.

PMID- 9231039
TI  - Contrasting structure of the saphenous vein and internal mammary artery used as
      coronary bypass vessels.
AB  - OBJECTIVES: To report quantitatively on the three-dimensional layered
      organization of the collagen and smooth muscle component of the two most
      successful vessels for coronary bypass-the internal mammary artery (IMA) and the
      long saphenous vein (SV). Our aim was to provide an explanation for the
      differential structural stiffness of these two vessels (both functioning at
      arterial pressures in their new environment), and how they might be susceptible
      to endothelial thickening. METHODS: Eleven human saphenous veins and 23 internal
      mammary arteries were fixed at arterial distending pressure of 110 mmHg, and were
      sectioned in cross-section at 7 microns thickness. A subset of these was also
      sectioned tangentially. Measurements of the three-dimensional alignment of
      collagen and smooth muscle fibers within the vessel wall were made using
      polarized light microscopy and the universal stage attachment. Data were plotted
      and analysed using circular statistics. RESULTS: The IMA, structured like an
      elastic artery, is dominated by a media with discrete lamellae of wavy collagen
      and smooth muscle, aligned nearly circumferentially, with a low variability of
      alignment (mean circular SD 12 degrees). The SV is more variable in its size and
      structure, characteristically with a narrow circumferential media comprised
      mostly of collagen which is straightened and highly aligned at arterial pressures
      (mean circular SD 9 degrees). Circumferential collagen in the vein was often
      adjacent to longitudinal bundles of smooth muscle and collagen. CONCLUSIONS: The
      strikingly aligned structure of the SV complements the known high mechanical
      stiffness of this vessel when at arterial distending pressure. The high fraction
      of longitudinal muscle, in addition to the circumferential muscle cells in the SV
      make it vulnerable to any pre-implant surgical preparation, and to the cyclical
      luminal pressures and longitudinal strains characteristic for epicardial
      arteries.

PMID- 9231040
TI  - Dyslipidemia and endothelium-dependent relaxation in internal mammary arteries
      used for coronary bypass surgery.
AB  - OBJECTIVE: Impairment of endothelium-dependent relaxation is related to
      dyslipidemia and may be an early marker for atherosclerosis in angiographically
      smooth arteries. The aim of the present study was to relate preoperative serum
      lipids to endothelium-dependent relaxation in internal mammary arteries of
      patients undergoing coronary bypass surgery. METHODS: The study group consisted
      of 37 patients, from whom segments of the internal mammary artery were obtained
      during surgery. Measurements of endothelium-dependent relaxation were performed
      in organ baths by adding methacholine (10 nM-10 microM). RESULTS: All internal
      mammary arteries dilated in response to methacholine, ranging from 4 to 112% of
      the precontraction to 10 mumol phenylephrine. In a multiple regression model,
      increased total serum cholesterol appeared to be the best predictor for impaired
      endothelium-dependent relaxation. A 1 mmol increase of total cholesterol was
      associated with a 11.2% decrease of endothelium-dependent relaxation (P = 0.006).
      When total cholesterol was omitted from the model, LDL-cholesterol became the
      best predictor of endothelium-dependent relaxation (regression coefficient
      10.3%/mmol; P = 0.02). No other variable was significantly associated with
      endothelium-dependent relaxation, and none of the preoperative variables was
      associated with endothelium-independent relaxation, expressed as the response to
      sodium nitrite (10 mM). CONCLUSION: Our study showed that endothelium-dependent
      relaxation in apparently non-diseased internal mammary arteries used for coronary
      bypass surgery was independently related to preoperative (LDL)-cholesterol
      levels.

PMID- 9231041
TI  - Chronic ACE inhibition by quinapril modulates central vasopressinergic system.
AB  - OBJECTIVE: The role of the brain as a target for angiotensin converting enzyme
      (ACE) inhibitors in the treatment of heart failure and hypertension is unclear.
      To test the hypothesis that ACE inhibitors may modulate other central
      neuropeptide systems such as the central vasopressin system, we studied the
      effects of chronic treatment with the ACE inhibitor, quinapril, on ACE activity
      and on central vasopressin content in specific brain areas in rats. METHODS: 22
      rats were chronically treated with quinapril (6 mg.kg-1 BW per gavage daily for 6
      weeks; untreated controls, n = 14). ACE density in various brain regions was
      assessed by in vitro autoradiography using the specific ACE inhibitor, 125I-351A.
      Vasopressin content was determined in 19 brain areas (micropunch technique) known
      to be involved in cardiovascular regulation. RESULTS: Following chronic quinapril
      treatment ACE was significantly decreased in the thalamus (-38%), hypothalamus (
      37%), hypophysis (-35%), cerebellum (-36%) choroid plexus (-20%), and locus
      coeruleus (-35%). Additionally, a marked reduction in serum ACE activity (-97%)
      was observed. Plasma levels of vasopressin were significantly decreased after
      quinapril treatment (0.97[s.e.m. 0.11] vs. 1.63[0.24] pg.ml-1 in controls, P <
      0.05). Vasopressin content was significantly reduced in 9 of 19 specific brain
      areas. Regarding the hypothalamic vasopressin-producing nuclei, vasopressin was
      decreased in the paraventricular (292[197] vs. 2379[585] pg.mg-1 crotein in
      controls; P < 0.001) and supraoptic nuclei (13618[1979] vs. 24525[3894] pg.mg-1
      protein; P < 0.05), but not in the suprachiasmatic nucleus. Vasopressin content
      was significantly reduced in brain areas connected by vasopressinergic fibres
      originating in the hypothalamic paraventricular nucleus: namely central gray,
      subcommissural organ, organum vasculosum laminae terminalis, dorsal raphe
      nucleus, and locus coerules. Vasopressin content was also significantly reduced
      in the median eminence (5887[1834] vs. 28321[4969] pg.mg-1 protein, P < 0.001),
      where the hormone is mainly concentrated in the hypothalamo-hypophysial tract.
      CONCLUSIONS: Autoradiographic studies in vitro indicate that orally administered
      quinapril suppresses central ACE activity after chronic treatment. ACE inhibition
      by quinapril strongly influences vasopressin content in important brain areas
      which are involved in central cardiovascular regulation. Therefore, central
      modulatory effects of ACE inhibitors may also contribute to overall therapeutic
      efficacy.

PMID- 9231042
TI  - Transesophageal multiplane imaging of the human pulmonary artery: a comparison of
      MRI and multiplane transesophageal two-dimensional echocardiography.
AB  - OBJECTIVE: To evaluate the anatomical relationship between the esophagus and
      pulmonary artery including assessment of the correct transesophageal Doppler
      insonation angle into the mid-pulmonary artery trunk. METHODS: We evaluated the
      anatomical relationship between the esophagus and pulmonary artery (PA) from
      comparable magnetic resonance (MR) and transesophageal echocardiographic (TEE)
      multiple two-dimensional images (0 degree, 45 degrees, 90 degrees and 135 degrees
      clockwise rotation of the standard transverse scanning plane when seen bearfrom
      the esophagus) obtained in 10 healthy, young volunteers. RESULTS: The main PA
      could be visualized with both techniques in all 10 volunteers and provided highly
      identical images of good quality. A mean insonation angle of 35 degrees (range 26
      degrees-46 degrees) for a fictive esophageal Doppler beam into the main PA was
      disclosed. The PA trunk was short with a mean length of 23.4 mm (range 17-30 mm).
      CONCLUSIONS: These anatomical data contradict the general assumption of alignment
      of the pulmonary artery and the transesophageal Doppler beam. Angle correction
      should be applied in the clinical setting using MTEE by rotation of the scanning
      plane to approximately 45 degrees. Ignoring the insonation angle of approximately
      35 degrees may cause 20% underestimation of blood flow velocity and cardiac
      output in the PA.

PMID- 9231043
TI  - Non-specific inhibition by human lipoproteins of endothelium dependent relaxation
      in rat aorta may be attributed to lipoprotein phospholipids.
AB  - OBJECTIVE: In vitro incubation of low-density lipoprotein (LDL) is reported to
      attenuate endothelium dependent relaxation mediated by acetylcholine (ACh) while
      not affecting endothelium-independent relaxation. This study was designed to
      examine the effects of other lipid-carrying lipoproteins as well as to study
      their effects on responses mediated by endothelium dependent agonists other than
      ACh. METHODS: The effects of human LDL, very-low-density lipoprotein (VLDL) and
      high density lipoprotein (HDL) on endothelium-dependent relaxation by ACh,
      histamine and the calcium ionophore, A23187, and endothelium-independent
      relaxation by sodium nitroprusside (SNP) were investigated is rat isolated aortic
      rings. The effects of combined LDL and HDL incubation on responses mediated by
      ACh were also examined. Control experiments included experiments examining the
      effects of bovine serum albumin on responses mediated by ACh. Thiobarbituric-acid
      reactive substances (TBARS) measured before and after organ bath incubation
      indicated little oxidation of the lipoproteins used. RESULTS: Maximal responses
      to ACh were inhibited by LDL, VLDL and HDL (0.02 and 0.2 mg protein/ml), to
      histamine by LDL (0.2 mg protein/ml), VLDL (0.02 and 0.2 mg protein/ml) and HDL
      (0.02 mg protein/ml) and to A23187 by LDL (0.2 mg protein/ml). VLDL (0.2 mg
      protein/ml) and HDL (0.02 and 0.2 mg protein/ml). A small but significant
      correlation (r = 0.54, P = 0.01) was observed between the level of inhibition of
      the endothelium-dependent responses and lipoprotein phospholipid concentration in
      the organ bath but not between the level of inhibition and cholesterol (free and
      esterified) or triglyceride concentrations. Responses to SNP were unaffected by
      LDL, VLDL and HDL. Combined incubation of tissues with LDL (0.2 mg protein/ml)
      and HDL (0.2 mg protein/ml) significantly increased maximal responses to ACh (pre
      lipoproteins 81.8 +/- 5.7 vs plus-LDL/HDL 100 +/- 0.0; P < 0.05). Bovine serum
      albumin had no effect on the maximal responses to ACh. CONCLUSIONS: We conclude
      that inhibition by human lipoproteins of endothelium-dependent agonists occurs
      with LDL, HDL and VLDL and suggest that this may be due to the phospholipid
      content of each lipoprotein. However, combined incubation of HDL with LDL negates
      this effect and an increased maximal response to ACh is reported.

PMID- 9231045
TI  - More about adenosine and arrhythmias.

PMID- 9231044
TI  - Homocysteine induces synthesis of a serine elastase in arterial smooth muscle
      cells from multi-organ donors.
AB  - OBJECTIVES: In heart transplant recipients with diffuse coronary arteriopathy, we
      have previously demonstrated the prevalence of elevated homocysteinemia, also
      known as an independent risk factor for myocardial infarction and stroke. In
      hyperhomocysteinemic mini-pigs we also observed early detectable pathologic
      changes in the elastic laminae. We hypothesized that homocysteine causes
      premature breakdown in the arterial elastic fibers by activation of the
      elastolytic activities. METHODS: We examined the effect of homocysteine on
      elastase-like production by smooth muscle cells from sub-inguinal arteries of
      multi-organ donors (23.4 +/- 3.4 yr, n = 8). The freshly isolated cells were
      incubated for 0-72 h with homocysteine (0-250 microM), in the presence or absence
      of specific protease inhibitors. RESULTS: Homocysteine was devoid of a direct
      effect, but after 18 h incubation the elastase-like activities increased by 5-6
      fold in the extracellular medium. The enzymes were characterized as serine
      proteases. Incubation of cells with a nucleic acid synthesis inhibitor
      (actinomycin D) or a protein synthesis inhibitor (cycloheximide) suppressed the
      enzyme induction. CONCLUSIONS: This is the first report of serine protease
      induction by homocysteine in vascular smooth muscle cells. The process may
      require protein synthesis and account for the early alterations of the arterial
      elastic structures in heart transplant recipients, and in other
      hyperhomocysteinemic patients, as well.

PMID- 9231046
TI  - Standardization of human follicle-stimulating hormone for therapy and diagnosis:
      report of an International Workshop, National Institute of Biological Standards &
      Control, UK, 21-22 March 1996.

PMID- 9231047
TI  - A comparison of different methods for diagnosing acromegaly.
AB  - OBJECTIVE: The present study was designed to assess the diagnostic value of
      different single measurements in comparison to the classic time-consuming method,
      the oral glucose tolerance test (OGTT), in acromegaly. DESIGN, PATIENTS AND
      MEASUREMENTS: IGF-I, free IGF-I, 24-hour-urinary GH (uGH), serum IGFBP-3 and 24
      hour-urinary IGFBP-3 (uIGFBP-3) were measured in 12 patients with untreated
      active acromegaly, in 29 patients who had been treated but were not cured, in 13
      patients with cured acromegaly and in 14 healthy control subjects, and compared
      with the results of the OGTT. RESULTS: In all patients with active acromegaly,
      whether they had been treated or not, nadir GH in OGTT was > 3 mU/l, whereas
      nadir GH was < 1.8 mU/l in the cured patients and the control subjects. In
      patients with untreated active acromegaly IGF-I, free IGF-I, uGH and IGFBP-3, but
      not uIGFBP-3, were significantly higher than in healthy individuals (P < 0.0001).
      Only IGF-I values did not overlap with the control group. In those patients with
      acromegaly who had been treated but not cured these parameters overlapped with
      the control group. In patients with acromegaly there was a significant
      correlation between nadir GH levels in OGTT and IGF-I (r = 0.71), free IGF-I (r =
      0.76), IGFBP-3 (t = 0.73) and uGH (r = 0.81) (P < 0.0001), but no correlation
      with uIGFBP-3. CONCLUSIONS: Only be means of the OGTT could patients with active
      acromegaly be completely distinguished from the control subjects and from cured
      patients. IGF-I, free IGF-I, IGFBP-3 and uGH were useful in the diagnosis of
      acromegaly, but of limited value in the follow-up of acromegalic patients after
      treatment. The determination of free IGF-I, which has yet not been investigated
      in acromegaly, offered no advantage over that of total IGF-I and IGFBP-3; uIGFBP
      3 was not useful in the diagnosis of acromegaly.

PMID- 9231048
TI  - Absence of desensitization by hexarelin to subsequent GH releasing hormone
      mediated GH secretion in patients with anorexia nervosa.
AB  - OBJECTIVE: Both the basal levels and the neuroregulation of GH secretion are
      perturbed in patients with anorexia nervosa. It is unknown if these alterations
      are due to severe undernutrition or if they reflect basic neurotransmitter
      alterations of the patient's neural pathways. On the other hand, prior
      administration of the GH secretagogue hexarelin in normal subjects blocks the GH
      releasing capability of GH releasing hormone (GHRH) administered 2 hours later.
      In the present work a sequential test was performed using the administration of
      hexarelin as first stimulus followed 120 minutes later by GHRH. The two aims of
      the study were: (a) to evaluate the interaction of GHRH and hexarelin, and (b) to
      further understand the alterations in GH neuroregulation in patients with
      anorexia nervosa. DESIGN: The GH stimuli used were hexarelin (1 micrograms/kg
      i.v.), a GH stimulus whose main action is hypothalamic, followed 120 minutes
      later by GHRH (1 micrograms/kg i.v.) as a pituitary stimulus. Each woman was
      tested once. PATIENTS: Thirty-two woman matched for age participated in the
      study: six normal-weight women as controls, 14 women with anorexia nervosa, seven
      women with secondary amenorrhoea due to voluntary weight loss for aesthetic
      reasons, and five normal-weight women after 72 hours of a controlled hypocaloric
      diet (800 cal/day). MEASUREMENTS: Plasma GH levels were measured by time-resolved
      fluoroimmunosasay, each value shown is the mean +/- SE in mU/l. RESULTS: The
      administration of hexarelin to the normal-weight women induced a clear-cut GH
      secretion (expressed as mean +/- SE of GH peak in mU/l of 77.5 +/- 21.8, but
      blocked the GH-releasing capability of GHRH administered 120 minutes later (6.6
      +/- 2.8, P < 0.05). In contrast, the women with anorexia nervosa showed a normal
      GH response after the two stimuli: hexarelin 64.8 +/- 9.2. GHRH 71.1 +/- 14.2.
      The absence of heterologous desensitization was specific to anorexia nervosa,
      because the women with amenorrhoea due to voluntary weight loss but with a normal
      energy intake showed a pattern similar to the controls (GH after hexarelin 60.3
      +/- 9.5 and to GHRH 120 minutes later 6.2 +/- 1.0 (P < 0.05)). Similarly, the
      women after the short-term hypocaloric diet showed a hexarelin-mediated GH
      secretion of 99.6 +/- 17.8, which blunted the subsequent administration of GHRH
      (GH mean peak of 9.9 +/- 2.9, P < 0.05 vs hexarelin). CONCLUSIONS: In the normal
      subjects, the administration of hexarelin induced clear-cut GH secretion, but
      inhibited the action of GHRH when administered 120 min later, while this
      heterologous desensitization was not observed in the patients with anorexia
      nervosa. This sequentially delayed test may be of some value in the clinical
      setting for assessing the status of patients with anorexia nervosa.

PMID- 9231049
TI  - The thyroid gland in acromegaly: an ultrasonographic study.
AB  - OBJECTIVE: An association between acromegaly and goitre is well recognized. We
      have studied the incidence and morphology of goitre in acromegaly, and examined
      the role of IGF-I and TSH in goitre pathogenesis. DESIGN AND SUBJECTS: Thirty
      seven subjects with acromegaly, active or in remission, were assessed by
      ultrasound to determine thyroid volume (TV) and morphology, and compared with
      normal controls. Nine subjects with acromegaly were also studied again following
      treatment with octreotide for 1 year. RESULTS: Compared with controls, TV was
      greater (28.7 +/- 18.3 ml vs 5.4 +/- 2.6 ml, P < 0.001) and IGF-I levels were
      higher (62.0 +/- 34.8 nM vs 28.9 +/- 10.9 nM, P < 0.001) in subjects with
      acromegaly. Those with active disease tended to have larger glands (30.0 +/- 17.2
      ml vs 22.2 +/- 16.7 ml, P = 0.18). The overall incidence of goitre was 92%.
      Twenty-seven subjects (73%) had nodules or heterogeneous thyroid echotexture.
      Subjects with nodular goitre had a longer duration of acromegaly than those with
      homogeneous glands (12.1 +/- 5.7 vs 7.6 +/- 4.0 years, P = 0.032). Those with
      nodular glands also had larger goitres than those with homogeneous glands (35.2
      +/- 18.8 ml vs 19.5 +/- 11.9 ml, P = 0.032). Thyroid volume correlated with IGF-I
      levels (r2 = 0.38, P = 0.002) and body mass index (r2 = 0.24, P < 0.001), and
      there was an inverse relationship with TSH levels (r2 = 0.46, P = 0.032).
      Patients studied again after treatment with octreotide for 1 year had a reduction
      in TV from 32.6 +/- 16.1 to 27.6 +/- 17.0 ml (P = 0.041). CONCLUSIONS: This study
      confirms that goitre is a common finding in acromegaly. Our findings suggest that
      early in the course of the disease, diffuse goitre occurs. Subsequently, thyroid
      autonomy and nodule formation develop, and further growth may occur independent
      of TSH. With control of GH hypersecretion, a reduction in thyroid size occurs,
      but this may be limited by the extent of thyroid nodularity.

PMID- 9231050
TI  - A CTLA-4 gene polymorphism is associated with both Graves disease and autoimmune
      hypothyroidism.
AB  - OBJECTIVE: The autoimmune thyroid diseases, Graves disease and autoimmune
      hypothyroidism, result from a complex interaction between genetic, environmental
      and endogenous factors. The genetic loci conferring susceptibility remain
      unclear. A recent report has demonstrated an association between a microsatellite
      polymorphism of the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves'
      disease in Caucasian patients in the USA. The aim of the present study was to
      confirm this association in UK patients and to determine whether this
      polymorphism is also associated with autoimmune hypothyroidism. DESIGN: Analysis
      of Caucasian patients with autoimmune thyroid disease from a single clinic,
      compared to local Caucasian controls. PATIENTS: We studied 112 patients with
      Graves' disease, 44 with autoimmune hypothyroidism and 91 controls. MEASUREMENTS:
      CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain
      reaction amplification of genomic DNA and resolution of the products on
      sequencing gels. RESULTS: As in previous studies, 21 alleles of the CTLA-4
      microsatellite region were detected. Allele 106 was significantly increased in
      patients with Graves' disease (P = 0.006) and in those with autoimmune
      hypothyroidism (P = 0.02) when compared to controls. There was no significant
      difference between the groups in the distribution of the other alleles and no
      association between allele 106 and sex, HLA-DR or -DQ specificities or the
      presence of ophthalmopathy in the Graves' patients. CONCLUSIONS: These results
      confirm that the CTLA-4 gene, or one closely associated with it, confers
      susceptibility to Grave's disease but is not specific as the CTLA-4 106 allele is
      also associated with autoimmune hypothyroidism. This association seems to be with
      autoimmune thyroid disease in general.

PMID- 9231051
TI  - Combined beta FSH and beta LH response to TRH in patients with clinically non
      functioning pituitary adenomas.
AB  - OBJECTIVE: 'Paradoxical' responses of LH, FSH, alpha-subunits and beta LH to TRH
      have previously been reported in individuals with clinically non-functioning
      pituitary tumours (NFT). The present study was designed to assess the in vivo and
      in vitro responses of beta FSH to TRH in NFT. We further examined the possibility
      that a TRH challenge with combined measurement of beta FSH and beta LH will
      identify a common anomalous secretory pattern in patients with NFT. DESIGN,
      PATIENTS AND MEASUREMENTS: Forty patients with NFT underwent a standard TRH test
      (400 micrograms intravenously). Blood samples for the determination of beta FSH,
      beta LH, FSH and LH were collected prior to TRH as well as 15, 30, 45, 60 and 90
      minutes following injection. Additionally, cultured adenomatous cells from eight
      to these patients were exposed to TRH in the absence and presence of octreotide
      and gonadotropin subunits were determined. RESULTS: TRH elicited a marked rise in
      circulating beta FSH in 29 of 40 individuals and in beta LH in 28 of 36 patients
      with NFT. In a subgroup of eight individuals whose tumours were harvested during
      surgery and cultured for 7-21 days, TRH increased beta FSH or beta LH and alpha
      subunit release in cultured adenomatous cells in all cases, including tumours
      from subjects not responding to TRH in vivo. In this subgroup of patients
      octreotide inhibited basal beta FSH secretion but not basal beta LH secretion
      both in vivo and in primary cultures of NFT cells. Both the in vivo and in vitro
      beta FSH, beta LH and alpha-subunit responses to TRH were entirely inhibited by
      octreotide. In all, 38 of the 40 subjects could be identified by either elevated
      basal beta FSH or beta LH levels and/or an abnormal rise in either beta FSH or
      beta LH in response to TRH. CONCLUSION: The measurement of basal and TRH
      stimulated beta-FSH and beta-LH levels identifies an abnormal hormonal secretory
      pattern in the vast majority (> 90%) of patients with clinically nonfunctioning
      pituitary tumours.

PMID- 9231052
TI  - Triiodothyronine (T3) reflects renal graft function after renal transplantation.
AB  - OBJECTIVE: Abnormalities in thyroid function are observed in patients with end
      stage renal disease. However, there are no data available evaluating sequential
      changes of thyroid function after renal transplantation. Therefore, we have
      studied thyroid hormone function in the immediate post-operative period after
      renal transplantation in order to determine the relationship between improving
      renal function and changes in thyroid hormone economy. DESIGN AND PATIENTS:
      Thyroid function was evaluated in 22 patients before and on days 1, 3, 7 and 15
      after renal transplantation. All patients received prednisone and cyclosporin as
      immunosuppressive therapy. Twelve patients with normal renal function undergoing
      comparable surgical procedures served as a control group. MEASUREMENTS: Serum
      creatinine and thyroid hormone parameters (total T4, total T3, free T4, free T3,
      thyroxin binding globulin (TBG), reverse T3, T3 sulphate and TSH) were measured.
      RESULTS: According to post-operative kidney function after renal transplantation,
      patients could be subdivided into three groups: five patients had primary graft
      function (group I); seven patients had delayed graft function because of acute
      renal failure (group II); 10 patients had delayed graft function requiring high
      doses of prednisone and some also of OKT3 because of acute rejection (group III).
      There was a significant fall in T3 and T4 concentrations with a concomitant rise
      in reverse T3 in all patients up to 3 days after renal transplantation. However,
      only patients in group I reached pre-operative values on day 15 after renal
      transplantation (serum creatinine 167 +/- 52 microM), whereas patients in group
      II (creatinine 609 +/- 118 microM) and group III (creatinine 839 +/- 71 microM)
      continued to have T3 concentrations well in the hypothyroid range (group I, 1.68
      +/- 0.28 nM) vs 0.87 +/- 0.09 nM in group II and 0.76 +/- 0.10 nM in group III; P
      < 0.01). Serum T4 concentrations were also low in group III (47.7 nM vs 100.2 nM
      in group I; P < 0.05) 15 days after renal transplantation. These changes were
      accompanied by a concomitant fall in T3/TBG ratio and in free T3. Elevated
      reverse T3 returned to normal values in all groups on the 15th day after renal
      transplantation. TSH fell significantly on the first post-operative day, but did
      not return to pre-operative values in renal transplantation patients. In the
      control group, TSH did not change during the study period. T3 sulphate, known to
      be elevated in chronic renal failure, remained above normal in all patients
      irrespective of graft function during this study period. CONCLUSIONS: T3
      concentrations reflect renal graft function after renal transplantation. T3 is
      below normal in patients with delayed graft function (acute renal failure or
      acute rejection). The post-operative period (up to 3 days after renal
      transplantation) is associated with a low T3 syndrome. TSH does not return to pre
      operative values even in patients with primary graft function. This might be due
      to the administration of prednisone. T3-sulphate is elevated before and after
      renal transplantation irrespective of graft function.

PMID- 9231053
TI  - Treatment of radiation-induced growth hormone deficiency with growth hormone
      releasing hormone.
AB  - In children with hypothalamic causes for GH deficiency there are theoretical
      reasons why a GHRH analogue might be better than conventional GH therapy in
      promoting growth. OBJECTIVE: We have aimed to determine the efficacy and safety
      of growth hormone-releasing hormone (GHRH) (1-29)-NH2 given as a twice daily
      subcutaneous injection in the treatment of growth failure in children with
      radiation-induced GH deficiency. DESIGN: A multicentre study comparing growth
      before and after 1 year of treatment with GHRH (1-29)-NH2, 15 micrograms/kg twice
      daily, by subcutaneous injection in children with radiation-induced GH
      deficiency. On completion of the study year all children were treated with GH
      (0.5 U/kg/week) and growth parameters were documented over the next year.
      PATIENTS: Nine children (six boys) with radiation-induced GH deficiency following
      cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant
      from the hypothalamic-pituitary axis (n = 8) or prophylaxis against central
      nervous system leukaemia (n = 1) were studied. All were prepubertal when the
      study commenced, which was at least 2 years from radiotherapy. MEASUREMENTS:
      Anthropometry and pubertal staging were carried out at 3-monthly intervals and
      bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing
      height velocities were compared with values during the year of GHRH treatment and
      then after the first year of GH therapy. In those that had received craniospinal
      irradiation, a change in leg-length Standard deviation score (SDS) was noted
      before and after GHRH therapy. Changes in skin-fold thickness and bone age during
      the GHRH study year were documented. Adverse events and 3-monthly measurements of
      clinical chemistry, haematology, lipid profile and thyroid function were
      recorded. RESULTS: There was a significant increase in height velocity from 3.3
      (SD 1.1) cm/year before treatment, to 6.0 (SDS 1.5) cm/year after 1 year of GHRH
      treatment (P = 0.004). GHRH maintained or improved the leg length SDS in children
      who had received craniospinal irradiation. Bone age increased by a mean of 1.1
      years/chronological year during treatment with GHRH. Subsequent height velocity
      during 1 year of GH therapy was 7.5 (SD 1.5)cm/year. No adverse changes in
      biochemical or hormonal analyses were noted or adverse events that could be
      attributed to GHRH therapy. One child went into puberty during the GHRH study
      year and three were pubertal during the first year of GH therapy. CONCLUSION: In
      cranially irradiated children, GHRH was effective in increasing growth velocity
      but this was less than that seen in response to GH therapy, although it matched
      that in children with isolated idiopathic GH deficiency treated with the same
      dose and schedule of GHRH administration.

PMID- 9231054
TI  - Insulin-like growth factor-I in growth hormone-deficient adults: relationship to
      population-based normal values, body composition and insulin tolerance test.
AB  - BACKGROUND: Although an insulin tolerance test (ITT) is the most commonly used
      method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements
      of serum insulin-like growth factor-I (IGF-I) may also be of value. OBJECTIVE: To
      validate the use of serum IGF-I concentration in the diagnosis of GHD in adults.
      DESIGN: A cross-sectional study. PATIENTS: One hundred and four patients, 60 men
      and 44 women, with known pituitary disease and verified GHD based on ITT.
      MEASUREMENTS: Serum IGF-I was determined by radioimmunoassay after acid-ethanol
      extraction. Body composition was estimated with total body potassium combined
      with total body water assessments. RESULTS: According to age- and sex-adjusted
      population-based references values, 51 patients had serum IGF-I concentrations
      below -2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty
      seven per cent of the patients aged 41 years (25th percentile) or below and 39%
      of the patients aged 57 years (75th percentile) or above had serum IGF-I
      concentrations below -2 SD. Women had lower mean IGF-I SD scores than men (P <
      0.01). Serum IGF-I was correlated with peak GH response during ITT (r = 0.40; P <
      0.001), age (r = -0.27; P < 0.01), duration of hypopituitarism (r = -0.52; P <
      0.001), number of pituitary hormonal deficiencies (r = -0.35; P < 0.001), body
      cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak
      GH response during ITT correlated with spontaneous GH secretion, duration (P = 
      0.48; P < 0.001) and number of deficiencies (r = -0.50; P 0.001). CONCLUSION: The
      measurement of serum IGF-I concentrations is not suitable as a single diagnostic
      test for growth hormone deficiency in adults. Even as a screening test, its use
      appears to be limited, especially in elderly subjects. The serum level of IGF-I
      was influenced by several factors in addition to GH, such as age, gender,
      anthropodometry and serum insulin level. The peak GH response during the insulin
      tolerance test appears to be influenced to a lesser degree by these factors.

PMID- 9231055
TI  - Components of biological variation, including seasonality, in blood
      concentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy
      volunteers.
AB  - OBJECTIVE: There are few detailed studies of annual or seasonal variations in
      hormone concentrations in man. This study examines the components of biological
      variation, including seasonality, in plasma TSH, total T3 (TT3), free T4 (FT4),
      PRL, cortisol and testosterone in healthy volunteers. DESIGN: Monthly blood
      samplings for the assay of the above hormones were collected during one calendar
      year. SUBJECTS: Thirteen normal men and 13 normal women participated in the
      present study (mean age 38.7 +/- 13.4 years). MEASUREMENTS: Assays of TSH, TT3
      and FT4 were carried out by means of immunoradiometric assays (IRMA), PRL by
      ELISA, cortisol by a fluorescence immunoassay, and testosterone with RIA. The
      time series were analysed by means of (bivariate or multivariate) spectral and
      cosinor analyses. RESULTS: Significant annual, four-monthly and biannual rhythms
      were detected in serum TSH; the lowest TSH values were observed in spring. A
      significant annual rhythm was detected in TT3, with lower values in spring and
      summer than in the other seasons. The peak-trough differences in the yearly
      variation expressed as a percentage of the mean were 29.1% and 8.2% for TSH and
      TT3, respectively. The yearly variation in plasma cortisol was significantly
      different between men and women: in men, 5.9% of the variation was explained by
      an annual rhythm, while in women 14.7% was explained by the fourth and seventh
      harmonical wave. The peak-trough differences in the yearly variation in plasma
      cortisol were 17.6% and 31.8% in men and women, respectively. There were no
      significant seasonal rhythms in PRL, FT4 or testosterone. The
      intraindividual/interindividual CV values were: TSH 29.3/48.4%, TT3 9.4/ 18.5%,
      FT4 7.1/9.1%, PRL 39.2/65.0%, cortisol 21.7/ 46.2%, and testosterone 12.6/40.8%.
      CONCLUSIONS: The degree of individuality measured in the plasma hormones is such
      that conventional population-based reference ranges may not correctly identify
      major alterations in these hormones in individual subjects.

PMID- 9231056
TI  - The c-erbB-2/neu proto-oncogene in human pituitary tumours.
AB  - OBJECTIVE: The aetiology of most pituitary tumours remains unknown. We have
      examined the potential role of neu receptor proto-oncogene in human pituitary
      tumorigenesis. MATERIALS AND METHODS: Ten non-tumorous pituitary glands and 16
      morphologically characterized functional and clinically non-functioning pituitary
      adenomas were studied. Protein expression was examined by immunohistochemistry,
      mRNA expression by RT-PCR and competitive PCR, gene amplification by differential
      PCR, and point mutations by DNA sequencing. RESULTS: Cytoplasmic positivity for
      neu was identified in a few scattered cells of the non-tumorous adenohypophysis
      using an antibody to the intracytoplasmic domain of neu, but no membrane staining
      was found with an antibody to the extracellular domain; the latter is said to
      reflect gene amplification. mRNA transcript signals of the expected size were
      identified in the normal adenohypophysis and in all 16 adenomas examined. No
      increase in the degree of mRNA expression, however, was noted in the different
      tumour types compared to normal human pituitary tissue as determined by
      competitive PCR. As neu can be activated to an oncogene by a point mutation in
      the transmembrane region, nucleotide substitutions in this domain were
      investigated. Direct sequencing of codon 659 revealed no point mutations in any
      of the tumours. Furthermore, since amplification of neu has been noted in various
      human malignancies, DNA from these tumours was examined by differential PCR. No
      detectable differences were noted between the neu gene and the single-copy
      reference gene IFN-gamma. CONCLUSION: The neu gene is expressed in
      adenohypophysial cells and their tumours. In pituitary adenomas, this expression
      is not associated with gene amplification or activating mutations to suggest a
      direct role in pituitary tumorigenesis.

PMID- 9231057
TI  - Metyrapone pre-treated inferior petrosal sinus sampling in the differential
      diagnosis of ACTH-dependent Cushing's syndrome.
AB  - BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful investigative
      technique in the differential diagnosis of ACTH-dependent Cushing's syndrome.
      Diagnostic accuracy is improved by the administration of corticotrophin releasing
      factor (CRF) during the procedure to stimulate ACTH secretion. We hypothesized
      that, given the unavailability of CRF in Australia, stimulation of ACTH secretion
      from tumorous corticotrophs with metyrapone treatment before IPSS may be useful.
      AIMS: To describe our clinical experience with a novel diagnostic test, and to
      compare results between IPSS with and without metyrapone pre-treatment. SETTING:
      Metropolitan, Australian university teaching hospital. PATIENTS: 18 patients were
      studied on 21 occasions: three with Cushing's disease without metyrapone
      treatment prior to IPSS (M-), 11 with Cushing's disease with metyrapone
      pretreatment (M+), three with ectopic ACTH syndrome, and one with pseudo
      Cushing's syndrome. TREATMENT: Patients received oral metyrapone, median dose 750
      mg 6 hourly, for 24 h before IPSS. RESULTS: No major side effects were noted.
      Metyrapone increased serum 11-deoxycortisol concentration to a median of 400
      nmol/l (range 36-1310) on the morning of the test. Radiological confirmation of
      correct catheter placement was shown in 36/42 inferior petrosal sinuses (86%).
      Median peak central: peripheral ACTH ratios were 9.8 for M- pituitary adenomas
      (range 5.7-13.6), 12.9 for the technically successful M+ pituitary adenomas
      (range 8-54.1), and 1.6 for M+ ectopic ACTH syndrome cases (range 1.2-3.4).
      Repeat studies in unoperated patients with ectopic ACTH syndrome showed ratios <
      1.6. IPSS showed median peak ACTH concentrations of 190 ng/l for M- pituitary
      adenomas (range 83-205), 595 ng/l for the technically successful M+ pituitary
      adenomas (range 80-7630; P = 0.035 compared to M-), and 62 ng/l for M+ ectopic
      ACTH syndrome cases (range 47-220). IPSS correctly identified the pituitary
      source of ACTH production in all cases of Cushing's disease (except one technical
      failure where MRI revealed a lesion). MRI scanning correctly identified a lesion
      in 3/14 operated Cushing's disease cases. IPSS correctly lateralized 1/3 M- and
      7/8 M+ Cushing's disease cases where the procedure was technically successful and
      surgical descriptions adequate. Pituitary exploration revealed a visible lesion
      in 75% of cases corresponding to the side predicted by IPSS; 'blind' hemi
      hypophysectomy was performed on the side predicted from IPSS in the remainder.
      All cases of Cushing's disease were cured or improved following surgery, with a
      median follow-up of 2.8 years (range 0.7-5.9). CONCLUSIONS: Metyrapone pre
      treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH
      output from pituitary corticotroph adenomas. The technique has allowed accurate
      localization and treatment of pituitary corticotroph microadenomas.

PMID- 9231058
TI  - Expression of adrenocorticotrophic hormone receptor mRNA in human adrenocortical
      neoplasms: correlation with P450scc expression.
AB  - OBJECTIVE: Adrenocorticotrophin (ACTH) is the main hormone-regulating steroid
      secretion from the adrenal cortex. The ACTH receptor (ACTH-R) has recently been
      cloned, allowing systematic evaluation of its expression and function in adrenal
      tumorigenesis. We investigated ACTH-R and P450 side-chain cleavage enzyme
      (P450scc) mRNA expression in a variety of neoplastic adrenocortical tissues by
      Northern blot and reverse-transcriptase-PCR (RT-PCR). PATIENTS AND MEASUREMENTS:
      We studied tissue from eight normal adrenals, six diffuse adrenocortical
      hyperplasias in patients with ACTH-dependent Cushing's syndrome, 22 adrenal
      adenomas, six carcinomas and two carcinoma cell lines. Poly A mRNA was
      electrophoresed, immobilized on a nylon membrane and hybridized using alpha 32P
      CTP labelled human ACTH-R and P450scc cDNAs. RESULTS: Mean ACTH-R mRNA expression
      showed significant differences between groups (P = 0.0001), but appeared to be
      independent of plasma ACTH concentrations. Compared to normal adrenal (= 100 +/-
      12%), expression was low in non-functional adenomas (23 +/- 11%) and carcinomas
      (19 +/- 12%), intermediate in adrenocortical hyperplasias (88 +/- 6%) and
      cortisol-producing adenomas (81 +/- 15%) and high in aldosteronomas (175 +/-
      29%). In adenomas, ACTH-R mRNA expression correlated closely with the expression
      of P450scc mRNA(r = 0.8, P = 0.0001) suggesting regulation by similar factors.
      However, carcinomas and cancer cell lines did not show a positive correlation
      between these two parameters (r = -0.44, P = 0.3). CONCLUSIONS: We have
      demonstrated that plasma ACTH is not the major factor influencing ACTH-receptor
      mRNA expression in neoplastic adrenal tissue. In benign tumours of the adrenal
      cortex there was a close positive correlation between ACTH-receptor mRNA and
      P450scc mRNA which was missing in adrenocortical carcinomas, probably as a result
      of tumour dedifferentiation.

PMID- 9231059
TI  - Type III hyperlipidaemia with primary hypothyroidism: a unique clinical course of
      hyperlipidaemia during replacement therapy of thyroid hormone.
AB  - A patient is described with type III hyperlipidaemia and primary hypothyroidism
      who had a unique clinical course of hyperlipidaemia. The patient was a 65-year
      old man with primary hypothyroidism. His plasma total cholesterol, triglyceride
      and high density lipoprotein-cholesterol concentrations 1 year after starting
      thyroid hormone replacement therapy were 7.98, 4.04 and 0.72 mmol/l,
      respectively. His plasma apolipoprotein (apo) E level was 0.29 g/l and its
      phenotype was E2/2. Remarkably, this patient had no hyperlipidaemia before
      starting thyroid hormone replacement therapy but it became overt only after the
      hypothyroidism had been treated. Although we have not confirmed the mechanism for
      this, we speculate that a decrease in enzyme activities responsible for
      cholesterol production may have been sufficient to surpass the effect of
      apolipoprotein E2/2 and the decrease in enzyme activities involved in degrading
      and excreting plasma cholesterol, resulting in normolipidaemia.

PMID- 9231060
TI  - Galactorrhoea and amenorrhoea due to an intradural neurinoma originating from a
      thoracic intercostal nerve radicle.
AB  - A 42-year-old woman had galactorrhoea and amenorrhoea. Four years previously she
      complained of sensory disturbance of her legs, with galt disturbance. Serum PRL
      level was 1408 mU/l. Magnetic resonance imaging showed a spindle-shaped mass in
      the spinal canal at the level of the ninth thoracic vertebra. The tumour was
      removed and histologically was found to be a neurinoma originating from the right
      ninth intercostal nerve radicle. Soon after the operation, galactorrhoea,
      amenorrhoea and neurological symptoms disappeared. Prolactin levels normalized at
      346 mU/l. These findings indicate that hyperprolactinaemia occurred as a result
      of the stimulation of afferent fibres from an intercostal nerve in a patient with
      intradural neurinoma of the intercostal nerve radicle.

PMID- 9231061
TI  - In vivo and in vitro effects of somatostatin and insulin on glucagon release in a
      human glucagonoma.
AB  - Inhibition of pancreatic glucagon secretion has been reported to be mediated by
      glucose, insulin and somatostatin. As no human pancreatic alpha-cell lines are
      available to study in vitro the relative importance of insulin and glucose in the
      control of pancreatic glucagon release, we investigated a patient presenting with
      a malignant glucagonoma who underwent surgical resection of the tumour.
      Functional somatostatin receptors were present as octreotide administration
      decreased basal glucagon and insulin secretion by 52 and 74%, respectively. The
      removed tumour was immunohistochemically positive for glucagon, chromogranin A
      and pancreatic polypeptide but negative for insulin, gastrin and somatostatin.
      The glucagonoma cells were also isolated and cultured in vitro. Incubation
      experiments revealed that change from high (10 mM) to low (1 mM) glucose
      concentration was unable to stimulate glucagon secretion. A dose-dependent
      inhibition of glucagon release by insulin was however, observed at low glucose
      concentration. These findings demonstrate that insulin could inhibit glucagon
      secretion in vitro in the absence of elevated glucose concentrations. These data
      suggest, as observed in vivo and in vitro in several animal studies, that
      glucopenia-induced glucagon secretion in humans is not mediated by a direct
      effect of low glucose on alpha-cells but possibly by a reduction of insulin
      mediated alpha-cell suppression and/or an indirect neuronal stimulation of
      glucagon release.

PMID- 9231062
TI  - Comparison of tests of stress-related cortisol secretion in pituitary disease
      (Clinical Endocrinology 1996:45:135-40)

PMID- 9231063
TI  - Adrenal tumour associated with silent 21-hydroxylase deficiency in a male.

PMID- 9231064
TI  - Euro targeting in Leiden: the fourth meeting of the EWGT, University of Leiden,
      14-17 November 1996.

PMID- 9231065
TI  - Gene therapy for Parkinson's disease: current knowledge and future perspective.

PMID- 9231066
TI  - Gene therapy strategies for asthma.
AB  - Asthma is a disease which is increasing in frequency and severity despite the
      incontestable advances in the understanding of its physiology and treatment. New
      therapeutic strategies are therefore required and at the time when a new
      treatment, that of gene therapy, is giving hope for the treatment of so far
      incurable illnesses, it would seem to us to be useful to discuss the possible use
      of this treatment in severe asthma and in particular in the case of the most
      severe asthmatic patients requiring continuous oral steroid treatment (referred
      to as steroid-dependent). These patients are those who require particular medical
      attention, they often need to be admitted to hospital and they represent over 50%
      of the total costs associated with asthma. No satisfactory alternative therapy is
      currently available. In this regard, a variety of gene-based strategies have
      recently been proposed for inflammatory and immunologic disorders. It is thus the
      purpose of this review to consider its application to asthma therapy, although
      there are very few published works that directly bear on gene therapy linked to
      asthma. After a brief outline of the epidemiology of asthma, its genetics and the
      available animal models, we will focus on its immunopathology slanting the
      discussion towards the possibility of a gene-based treatment.

PMID- 9231067
TI  - Factors controlling the efficiency of cationic lipid-mediated transfection in
      vivo via intravenous administration.
AB  - The factors controlling the transfection efficiency of cationic lipid carrier
      systems following intravenous administration are poorly understood. Using N-[1
      (2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) combined with
      Tween 80 as a carrier system and cDNA of luciferase or beta-galactosidase gene as
      a reporter, we investigated the importance of DOTMA to DNA ratio and the ratio of
      DOTMA to Tween 80 in the lipid formulation in determining the site and level of
      transgene expression following intravenous administration. The data show that all
      of the internal organs, including lung, liver, spleen, heart and kidneys,
      expressed the transgene upon systemic administration into animals with 25
      micrograms of plasmid DNA when complexed with DOTMA-Tween 80 lipid formulation.
      The transfection efficiency was dependent on both DOTMA to DNA, and DOTMA to
      Tween 80 ratios. Among the organs examined, the lung appeared to be more
      transfectable than other organs. A better transfection activity was obtained with
      higher DOTMA to DNA and DOTMA to Tween 80 ratios. Time-response curve shows that
      gene expression was transient with a maximal level between 10 and 24 h after
      injection. Results from tissue distribution studies with 125I-labeled plasmid DNA
      and Southern analysis suggest that the transient expression is the result of the
      loss of transgene from the transfected cells. These results suggest that cationic
      lipid-based delivery systems can be efficient for gene delivery if the
      composition of the DNA-lipid complexes is properly controlled.

PMID- 9231068
TI  - Adenovirus-mediated gene transfer into monocyte-derived macrophages of patients
      with X-linked chronic granulomatous disease: ex vivo correction of deficient
      respiratory burst.
AB  - The underlying cause of X-linked chronic granulomatous disease (X-CGD) is
      mutations in the gp91phox coding gene. Gp91phox is the larger subunit of the
      cytochrome b558, the membrane-bound terminal redox centre of the respiratory
      burst oxidase (NADPH oxidase). We have constructed a recombinant adenovirus which
      contains a functional copy of the human gp91phox cDNA under the control of the
      cytomegalovirus (CMV) enhancer/promoter region. This vector was used to infect
      monocyte-derived macrophages of gp91phox-deficient CGD patients. Expression of
      the gp91phox transgene resulted in ex vivo reconstitution of the respiratory
      burst activity. Nitroblue-tetrazolium staining indicated that 74% of the patient
      cells could be phenotypically corrected when compared with a corresponding
      control culture of normal monocyte-derived macrophages. Adenoviral gene transfer
      may become a promising tool and gain therapeutical potential by the targeting of
      autologous monocytes. Genetically corrected autologous monocytes may be used for
      supportive treatment of X-CGD patients to overcome acute life-threatening
      infections. Establishment of adenovirus-mediated reconstitution of gp91phox
      deficient monocytes therefore represents a first step towards the development of
      a clinically applicable supportive transient somatic gene therapy in CGD.

PMID- 9231069
TI  - Intracellular inhibition of HIV-1 replication using a dual protein- and RNA-based
      strategy.
AB  - Exporting unspliced human immunodeficiency virus type 1 (HIV-1) RNA from the
      nucleus to the cytoplasm, through an interaction between the viral regulatory Rev
      protein and Rev response element (RRE) RNA, is a critical step in the HIV-1 life
      cycle. Disruption of either Rev or the RRE will completely inhibit HIV-1
      replication. As such, a strategy for somatic gene therapy to treat HIV-1
      infection by intracellular expression of an anti-HIV-1 Rev single chain variable
      fragment (SFv) and a ribozyme which specifically targets the RRE was developed.
      The anti-Rev D8SFv, which specifically targets the Rev activation domain, may be
      a key component of combination intracellular immunization, as it has been
      previously shown to potently inhibit Rev function, thereby inhibiting viral
      replication. In the present studies, different HIV-1 RRE region-specific
      hammerhead ribozymes were constructed and their anti-HIV-1 replication effects
      were assayed in diverse RNA polymerase (pol) II and III promoters and vector
      systems in cell culture. Utilizing this combination of an SFv and a ribozyme as a
      dual strategy to block HIV-1 replication, both at the protein and RNA level, data
      from these studies demonstrated that potent inhibition of HIV-1 replication can
      be achieved via this approach. Combination gene therapies hold promise, analogous
      to combination chemotherapeutic regimens, for the in vivo treatment of HIV-1
      infections.

PMID- 9231070
TI  - Employment of the mdr1 promoter for the chemotherapy-inducible expression of
      therapeutic genes in cancer gene therapy.
AB  - Numerous approaches in gene therapy of human cancers are focused on the
      establishment of cell type specific or inducible expression vectors allowing the
      targeted and regulated expression of therapeutic genes. Various conditionally
      active vectors have been created carrying promoters responding to certain factors
      or therapeutic modalities (eg hormones, irradiation). The promoter of the
      multidrug resistance gene (mdr1) harbors such responsive elements and two of
      these elements have been related to drug responsiveness. In earlier studies we
      and others have characterized the mdr1 drug responsive-element in CAT reporter
      assays demonstrating its inducibility by MDR-associated drugs. To exploit this
      property, we linked the mdr1 promoter sequence to the human tumor necrosis factor
      alpha (TNF) cDNA in a retroviral vector and transduced the vector into human
      mammary and colon carcinoma cell lines. These cells were treated with various
      mdr1-associated drugs to induce TNF expression in vitro. We have shown that the
      mdr1 promoter-driven TNF expression is drug-inducible and that this induction is
      drug concentration and time dependent. The studies demonstrate the feasibility of
      the novel vector system for a chemotherapy-inducible expression of a
      chemosensitizing cytokine that is successful at enhancing cytotoxicity of drugs
      in cancer therapy.

PMID- 9231071
TI  - Pathogenic lymphoid cells engineered to express TGF beta 1 ameliorate disease in
      a collagen-induced arthritis model.
AB  - Collagen-induced arthritis in DBA/1 mice is a model of rheumatoid arthritis with
      marked synovitis and erosions. The disease can be adoptively transferred to SCID
      mice with arthritogenic splenocytes from DBA/1 mice injected with bovine collagen
      type II. However, infection of arthritogenic splenocytes with a retrovirus
      expressing TGF beta 1 inhibits development of arthritis in SCID mice. When DBA/1
      mice, at onset of arthritis have additional arthritogenic splenocytes
      transferred, exacerbation occurs, reflected in a rapid increase in the number of
      arthritic joints, increased paw swelling and higher levels of anti-collagen
      antibody. By infecting arthritogenic splenocytes ex vivo with TGF beta 1
      retrovirus, this exacerbation was inhibited. TGF beta 1 was effective in lowering
      inflammation of joints with already established arthritis and inhibiting the
      spreading of the disease to other joints. Transient reduction in anti-collagen
      antibody levels could also be obtained using purified T cells infected with TGF
      beta 1 retrovirus. In addition, expression of TGF beta 1 in lymphocytes reduced
      the levels of gelatinase (MMP2) activity in inflamed joints.

PMID- 9231072
TI  - Potential of Varicella zoster virus thymidine kinase as a suicide gene in breast
      cancer cells.
AB  - To investigate the potential of the thymidine kinase gene from Varicella zoster
      virus (VZVtk) to act as a suicide gene, VZVtk was transferred via a dicistronic
      retroviral construct into MCF7, T-47D and MDA-MB-435 human breast cancer cells.
      The cytotoxicity of antiviral drugs was then evaluated in vitro on the wild-type
      and transduced cells. Acyclovir and ganciclovir did not show any selective
      toxicity for the modified cells. In contrast, (E)-5-(2-bromovinyl)-2'
      deoxyuridine (BVDU) was extremely toxic for the VZVtk expressing cells, with IC50
      values of 0.6 microM, 0.1 microM and 0.06 microM for MCF7, T-47D and MDA-MB-435
      cells, respectively. The selectivity index of BVDU (ie the IC50 value ratio of
      the wild-type to the VZVtk cells) was 400 for MCF7, 750 for T-47D and 2000 for
      MDA-MB-435 cells. To test the system in vivo, VZVtk carrying MDA-MB-435 cells
      were inoculated subcutaneously into nude mice. An intraperitoneal treatment with
      BVDU administered at the emergence of the tumors, led to a prolonged arrest of
      the tumor growth and a reduced tumor mass. This effect was BVDU dose-dependent.
      No bystander effect of BVDU killing could be demonstrated in vitro on mixed
      populations of VZVtk positive and negative MDA-MB-435 cells. However, an
      important bystander effect was observed in identical experiments performed on 9L
      rat gliosarcoma cells infected with the VZVtk-carrying vector. These results
      demonstrate the efficiency of VZVtk as a suicide gene when BVDU is used as
      prodrug. The bystander effect measured in vitro, depends however on the tumoral
      cell type used.

PMID- 9231073
TI  - Co-expression of the herpes simplex virus thymidine kinase gene potentiates
      methotrexate resistance conferred by transfer of a mutated dihydrofolate
      reductase gene.
AB  - We have previously shown that transfer of a mutated dihydrofolate reductase
      (DHFR) confers resistance to methotrexate (MTX) to infected cells. We report
      herein the construction of a retrovirus vector, DC/SV6S31tk, which carries the
      herpes simplex virus thymidine kinase gene (HSVtk) as well as the mutated Serine
      31 DHFR (S31) cDNA. 3T3 cells infected with DC/SV6S31tk are more resistant to MTX
      than cells infected with DC/SV6S31, which carries the S31 and Neo gene. In
      DC/SV6S31tk-infected cells, a fraction of cells (20-40%) were more resistant to
      MTX compared with DC/SV6S31-infected cells, and these cells survived a 5-day
      exposure to 200 microM of MTX. The mechanism of this augmented resistance is
      attributed to the salvage of thymidine by HSVtk, as the augmentation is reversed
      when dialyzed serum is used for cytotoxicity assays. The cells that survive high
      dose MTX selection have high levels of expression of S31 DHFR and HSVtk, although
      copy numbers of the proviral sequences do not increase significantly.
      Transduction of cells with the DC/SV6S31tk vector also sensitizes cells to
      ganciclovir (GCV). Co-expression of a metabolically related gene in a retroviral
      vector to potentiate the resistance imparted by a drug resistance gene may be
      useful for gene therapy for cancer patients.

PMID- 9231074
TI  - The bystander effect exerted by tumor cells expressing the herpes simplex virus
      thymidine kinase (HSVtk) gene is dependent on connexin expression and cell
      communication via gap junctions.
AB  - To elucidate the role gap junctions play in the bystander effect, we examined the
      cytotoxic effect of herpes simplex virus thymidine kinase (HSVtk) modified tumor
      cells on gap junction communication-deficient tumor cells and their connexin
      transfectants. Communication competent Walker 256 tumor cells engineered to
      express the HSVtk gene (Walker-tk+) when cocultured with N2A mouse neuroblastoma
      and PC12 rat pheochromocytoma cells with absent endogenous junctional conductance
      showed no bystander cytotoxicity. Transfection of N2A cells with the rat
      connexin37 gene (5Q) and PC12 cells with the human connexin43 gene rendered them
      susceptible to bystander cell death. Additionally, communication-deficient N2A
      cells transfected with the HSVtk gene failed to exert a bystander effect, whereas
      N2A transfectants coexpressing the connexin37 and HSVtk genes (5Qtk+ cells)
      exerted bystander cytotoxicity on gap junction communication-competent 5Q but not
      on communication-deficient N2A cells in vitro. In vivo experiments also showed
      tumor growth inhibition of communication-competent 5Q but not communication
      incompetent N2A cells by 5Qtk+ cells. In conclusion, these results indicate that
      in several cellular environments the bystander effect is dependent on connexin
      expression and gap junctional communication between HSVtk-positive and HSVtk
      negative cells.

PMID- 9231075
TI  - H1 and HMG17 extracted from calf thymus nuclei are efficient DNA carriers in gene
      transfer.
AB  - In this article we describe the chromatographic separation of acid nuclear
      protein fractions which have previously been shown to be active in DNA
      transfection experiments. By combining anionic and cationic ion exchangers, we
      were able to separate and identify some of the active proteins. In addition to
      HMG1, already known for its transfection activity, we have identified histone H1
      and HMG17 as further transfection-active proteins. The highest transfection
      activity was associated with H1 and another nonidentified protein showing a
      somewhat higher electrophoretic mobility than H1. We have also found that the
      presence of CaCl2 in a low concentration in the cell culture medium is an
      important requirement for transfection.

PMID- 9231076
TI  - Antiretroviral effect of a gag-RNase HI fusion gene.
AB  - We have previously shown that a molecule consisting of a fusion of a Ca(2+)
      dependent nuclease (from Staphylococcus aureus) to a retroviral coat protein
      specifies a potent antiviral specific for that retrovirus. Genes specifying such
      fusion proteins can be delivered to virus-susceptible cells, providing an
      antiviral gene therapy aimed at limiting virus spread. We report here the results
      of experiments to vary the nuclease moiety of such fusion proteins. We found that
      one nuclease. Serratia marcescens nuclease, was extremely toxic to host cells and
      hence not likely to be useful for therapeutic purposes. A second nuclease,
      Escherichia coli RNase Hl was found to be nontoxic and highly effective against a
      murine leukemia virus when it was fused to the leukemia virus coat protein. The
      fusion protein was enzymatically active and stably expressed, without apparent
      toxicity to host cells. Reduction in infectious virus output was as high as 97
      99%. These studies provide a model system for the development of gene therapeutic
      agents aimed at combating retroviral infections in vivo.

PMID- 9231077
TI  - Novel retroviral packaging cell lines: complementary tropisms and improved vector
      production for efficient gene transfer.
AB  - We report increased transduction of human hematopoietic progenitor cells through
      a combination of novel retroviral vector packaging cell lines, and improved
      vector supernatant production. The new ProPak packaging cell lines produce either
      murine leukemia virus (MLV) xenotropic (ProPak-X cells) or amphotropic particles
      (ProPak-A cells), and ProPak-based producer cells were demonstrated to be free of
      replication-competent retrovirus (RCR) by stringent testing. Vector supernatants
      from ProPak or existing packaging cell lines producing different pseudotyped
      particles (amphotropic MLV, xenotropic MLV or gibbon ape leukemia virus) were
      compared for the ability to transduce clinically relevant human hematopoietic
      cells. All vector types transduced primary human CD34-positive or CD4-positive
      cells, regardless of tropism. However, consistently higher transduction of target
      cells was achieved with ProPak-derived amphotropic vector than with PA317
      packaged amphotropic vector. The highest transduction of human hematopoietic
      progenitor cells was achieved with vector supernatant generated from a coculture
      of the ProPak-X and ProPak-A cell lines. This ping-pong amplification yielded
      supernatant containing vector targeted to two distinct receptors present on human
      cells, and did not result in detectable RCR formation. In addition, we describe
      conditions for improved vector supernatant production in a packed-bed bioreactor.

PMID- 9231078
TI  - Antibody to CD40 ligand inhibits both humoral and cellular immune responses to
      adenoviral vectors and facilitates repeated administration to mouse airway.
AB  - Adenoviral vectors have been used successfully to transfer the human CFTR cDNA to
      respiratory epithelium in animal models and to CF patients in vivo. However,
      studies done primarily in mice, indicate that present vector systems have
      limitations. Among other things, transgene expression in the lung is transient
      and the production of neutralizing antibodies against adenovirus correlates with
      a reduced ability to readminister a vector of the same serotype. Here we
      demonstrate that in mice, a transient blockade of costimulation between activated
      T cells and B cells/antigen presenting cells using a monoclonal antibody (MR1)
      against murine CD40 ligand inhibits the development of neutralizing antibodies to
      adenoviral (Ad) vector. MR1 also decreased the cellular immune response to Ad
      vector and allowed an increase in persistence of transgene expression.
      Furthermore, when administered with a second dose of Ad vector to mice
      preimmunized against vector, MR1 was able to interfere with the development of a
      secondary antibody response and allowed for high levels of transgene expression
      upon a third administration of vector to the airway.

PMID- 9231079
TI  - Copy number-dependent expression of a YAC-cloned human CFTR gene in a human
      epithelial cell line.
AB  - Initial studies for gene therapy of cystic fibrosis have used heterologous
      promoters to drive expression of the cystic fibrosis transmembrane regulator
      (CFTR) cDNA. An alternative approach would be to have constructs based on the
      endogenous promoter which could give tissue-specific and normal, regulated levels
      of expression. The DNA elements necessary for this remain unidentified so we have
      investigated CFTR expression from a 310 kb yeast artificial chromosome (YAC)
      clone which contains the intact human CFTR gene consisting of 27 exons spread
      over 230 kb of genomic DNA and also about 50 kb of 5' DNA. In order to
      distinguish the gene on the YAC, a restriction site change was introduced into
      the 3' untranslated region of the gene in the YAC. The YAC was then transferred
      into the human colonic adenocarcinoma cell line Caco-2 which expresses endogenous
      CFTR. The CFTR gene on the YAC was found to be well expressed in the Caco-2 cells
      and, in the two cell lines analysed, the ratio of YAC-derived mRNA to endogenous
      mRNA was the same as the ratio of YAC DNA to endogenous DNA. This indicates that
      each copy of the CFTR gene on a YAC integrated in the Caco-2 cells is being
      expressed at approximately the same level as each of the endogenous genes. Thus,
      the YAC clone contains all the long-range elements necessary to confer full
      levels of expression, independent of position of integration, in human Caco-2
      cells. Deletion of this YAC clone should allow the elucidation of the DNA
      elements controlling human CFTR expression and the development of constructs for
      gene therapy.

PMID- 9231081
TI  - Should ENT surgeons undertake pituitary surgery?

PMID- 9231080
TI  - Incorporation of beta-globin untranslated regions into a Sindbis virus vector for
      augmentation of heterologous mRNA expression.
AB  - Polynucleotide immunization has been employed as a means of inducing immune
      responses through the introduction of antigen-encoding DNA. While immunization
      against specific tumor antigens may be achieved through this strategy, various
      candidate tumor antigens may not be approached via DNA-based vaccines as they
      represent transforming oncogenes. As an alternative approach, we have explored
      the utility of mRNA vectors for polynucleotide immunization. The transient
      expression achieved by mRNA may provide an efficient and safe system for
      stimulating immune responses to tumor-specific antigens. Our previous work
      demonstrated that a self-replicating RNA enhances the magnitude and duration of
      transgene expression for this application. Here we further modify the vector for
      optimal use in gene therapy through the incorporation of untranslated regions
      flanking the encoded transgene. The beta-globin 5' and 3' untranslated regions
      (UTRs) were inserted directly flanking the luciferase gene in both nonreplicative
      and replicative RNA constructs. In both cases, elevated and prolonged levels of
      luciferase expression were detected from the beta-globin UTR-flanked luciferase
      as compared to luciferase without these sequences. These modifications improve
      the ability of replicative RNA vectors to produce high, yet transient transgene
      expression for cancer immunotherapy strategies.

PMID- 9231082
TI  - Visual evoked potentials in endoscopic and anterior skull base surgery: a review.
AB  - The anterior visual pathway can be damaged during surgery of the anterior skull
      base, the sellar and parasellar area, the orbit, or the paranasal sinuses.
      Clinical per-operative monitoring of the visual pathway is difficult and damage
      to the optic nerve is often only determined late. Visual evoked potentials may
      provide an early indication of reversible change to the visual system and various
      per-operative monitoring techniques have been used. These techniques show promise
      but at present they are too cumbersome and give results which are too variable to
      be reliable in per-operative monitoring.

PMID- 9231083
TI  - Revision myringoplasty.
AB  - This retrospective study was undertaken to review the short- and long-term
      results of 70 revision and 16 re-revision myringoplasty operations. Of the
      former, 43 cases (61.4 per cent) had initial success, six weeks following
      surgery. The leading causes of immediate failure (27 cases) were associated with
      a complete no-take of the graft, infection with graft necrosis and poor anterior
      adaptation of the graft in decreasing order. Six out of the 43 patients developed
      late re-perforations during the follow-up period, thus reducing the success rate
      of revision myringoplasty to 52.8 per cent. Late re-perforations were attributed
      to insidious atrophy of the tympanic membrane or episodes of acute otitis media.
      Sixteen patients underwent re-revision myringoplasty and their success rate was
      62.5 per cent. The overall success rate of revision and re-revision myringoplasty
      was 54.7 per cent. It has been concluded that results of revision myringoplasty
      were independent of patients' age, location and size of perforation and the
      seniority of the surgeon.

PMID- 9231084
TI  - Extensive cholesteatoma: long-term results of three surgical techniques.
AB  - During the years 1979-81, three different surgical techniques were used in the
      treatment of 87 ears with extensive cholesteatoma. All procedures were performed
      in one stage by the same surgeon. Ten to 13 years after the operations about 70
      per cent of ears operated on by the canal wall up technique had developed a new
      cholesteatoma, which in most cases was recurrent, or a deep retraction pocket. A
      modification of this technique with mastoid obliteration resulted in a similar
      failure rate. In contrast, ears operated on by the canal wall down technique (in
      most cases with mastoid obliteration) had acceptable stability with a long-term
      recurrence rate of about 15 per cent. Most patients in the canal wall down group
      had a dry ear without significant cavity problems. Hearing in these patients was
      as least as good as hearing in patients with a preserved canal wall. We conclude
      that a meticulous one-stage canal wall down technique in ears with extensive
      cholesteatoma results in a high percentage of unproblematic, stable ears with
      satisfactory function. In contrast, if the posterior canal wall is preserved,
      recurrent cholestealoma is the rule more than the exception.

PMID- 9231085
TI  - The Singapore swing.
AB  - The use of a rotation pedicled flap, entitled the 'Singapore Swing', comprising
      temporalis fascia and mastoid periosteum, is presented as a new method of
      promoting healing in 'open' mastoid surgery for chronic ear discharge. Cadaver
      studies show that the main blood supply of the flap is derived from a branch of
      the postauricular artery which enters the pedicle near the mastoid tip. A review
      of the first 14 operations showed complete healing with dry ears and intact
      tympanic membranes in all instances, three cases requiring secondary grafting of
      residual perforations. We consider the results sufficiently encouraging to merit
      an extended trial of the technique.

PMID- 9231086
TI  - Squamous cell carcinomas of the head and neck: descriptive analysis of 1293
      cases.
AB  - Medical reports of 1293 patients with squamous cell carcinoma (SCC) of the head
      and neck were retrospectively evaluated. The patients were classified according
      to their age, sex, primary tumour localization and tumoral stage. There were 1181
      males (91.3 per cent) and 112 females (8.7 per cent), with a male to female ratio
      of 10.5:1. The peak incidences for all primary tumour localizations were observed
      in the fifth decade. Most common primary tumour localizations were the larynx
      (71.1 per cent), the nasopharynx (10.1 per cent) and the oral cavity (8.8 per
      cent). Of all patients in whom staging was complete, 43.1 per cent presented at
      early and 56.9 per cent at advanced stages. The proportion of patients presenting
      with metastatic neck nodes was 34.4 per cent and the incidence of metastatic neck
      nodes increased with increasing T stage. The supraglottic region was the most
      common primary site among all laryngeal SCC, with a supraglottic to glottic SCC
      ratio of 1.5:1. Glottic SCC presented at earlier stages compared to supraglottic
      SCC. The incidence of nodal metastases increased with increasing T stage for SCC
      of the larynx, the oral cavity and the oropharynx.

PMID- 9231087
TI  - The use of Indermil (n-butyl cyanoacrylate) in otorhinolaryngology and head and
      neck surgery. A preliminary report on the first 33 patients.
AB  - The authors present their initial experience of a new sterile medical grade
      cyanoacrylate adhesive (Indermil) in otolaryngeal and head and neck surgery.
      Thirty-three patients who underwent a variety of head and neck operations
      consented to have their skin incisions closed using the adhesive and 10 of those
      also underwent repair of the tympanic membrane, either as part of tympanoplasty
      or mastoid surgery. The history of the use of this class of adhesive is presented
      with an explanation of the chemical properties of these compounds. Advantages of
      using cyanoacrylate adhesives and future possible applications in otolaryngology
      and head and neck surgery are discussed.

PMID- 9231088
TI  - Paediatric neck masses--a diagnostic dilemma.
AB  - Three hundred and sixty children who had a head and neck mass excised during 1987
      to 1992 at the Royal Hospital for Sick Children, Glasgow were studied. There were
      210 males and 150 females with a mean age of 60.7 months (0.5 to 198 months).
      Pilomatrixomata/sebaceous cysts (34 per cent), thyroglossal cysts (13 per cent),
      branchial remnants (nine per cent) and dermoids (nine per cent) accounted for
      almost two-thirds of the 264 non-lymphadenomatous benign lesions excised. Ninety
      three lymphadenopathy masses consisted of 60 with reactive hyperplasia, 21 with
      Mycobacterium infection and 12 lymphomas. There were three solid malignant
      tumours, two were rhabdomyosarcomata and one disseminated round cell tumour. The
      correlation between clinical diagnosis and histopathology of benign non-lymph
      node masses and solid tumours was 90 per cent and 100 per cent respectively, in
      benign lymph nodes, 66 per cent, but was poor in differentiating lymph node
      content. The mean time from presentation of a swelling to its excision was almost
      a year and the mean in-patient stay for excision of a mass was almost five days.
      The role of fine needle aspiration cytology (FNAC) in arriving at a diagnosis and
      reducing patient morbidity is discussed.

PMID- 9231089
TI  - Retropharyngeal abscess: a clinical review.
AB  - Retropharyngeal abscesses are uncommon but potentially lethal infections,
      especially in the paediatric population under the age of five years. Abscesses in
      this group are classically secondary to upper respiratory infections especially
      oropharyngeal infections, while in the adult group they are usually secondary to
      trauma, foreign bodies, or as a complication of dental infections. Early
      diagnosis and the wide spread use of antibiotics have made these infections less
      common today. Between the years 1985-1996, 19 cases of retropharyngeal abscesses
      were treated in our department. Factors such as age, sex, aetiology, presenting
      signs, symptoms, methods of diagnosis, treatment and complications were reviewed.
      Thirty-two per cent of the cases were secondary trauma. A lateral neck film
      showing widening of the prevertebral space was the most important diagnostic
      tool, computed tomography (CT) scan was used in 63 per cent of cases to verify
      the signs of an abscess and to provide more accurate anatomical localization.
      Thirteen cases required surgical drainage. The single most commonly-isolated
      pathogen was Streptococcus pyogenes. There were no deaths and only one recurrence
      requiring repeated surgical drainage. One case was complicated by a spinal canal
      abscess. We also report two cases of retropharyngeal abscess in children caused
      by swallowing of unusual foreign bodies.

PMID- 9231090
TI  - The evaluation of salivary gland tumours using proliferating cell nuclear
      antigen.
AB  - In order to assess its discriminating and prognostic value, we studied the
      immunoreactivity for proliferating cell nuclear antigen (PCNA) in tissue from 52
      human salivary gland tumours using the murine monoclonal antibody PC10. The PCNA
      percentage count, namely, the average number of positive nuclei counted per 100
      randomly selected tumour cells was recorded for each tumour. Anaplastic carcinoma
      was used as a positive control and histologically 'normal' salivary gland and
      tonsil served as a negative control. A PCNA count of 30 per cent was postulated
      to predict malignancy within a given salivary gland tumour i.e. a PCNA count of
      30 per cent or above would indicate malignant potential. This gave a sensitivity
      of 96.9 per cent and a specificity of 95.2 per cent and a positive predictive
      value of determining malignancy of 96.8 per cent. We conclude that PCNA
      immunoreactivity is useful in discriminating between benign and malignant
      salivary gland tumours and that it may have prognostic value in this diverse
      group of neoplasms.

PMID- 9231091
TI  - Parotidectomy. Preserving the posterior branch of the great auricular nerve.
AB  - The great auricular nerve is often sacrificed in superficial parotidectomy, even
      though its posterior branch often can be preserved. By cautious dissection of the
      great auricular nerve it is possible to preserve the posterior branch in 70.5 per
      cent of the operations. Ninety-five patients who had undergone superficial
      parotidectomy were included. A significantly higher number of patients had
      subjective sequelae if the posterior branch of the nerve had been cut, compared
      to the patients with a preserved nerve. A significantly higher rate of sensory
      morbidity was found if the nerve had been cut. In patients with a preserved
      posterior branch of the great auricular nerve there was no increase in other
      potential sequelae after parotidectomy. Therefore, this additional dissection
      should be considered, where appropriate, in routine parotid surgery.

PMID- 9231092
TI  - Aspergillus mastoiditis in a patient with acquired immunodeficiency syndrome.
AB  - We present the case history of a patient who was severely immunocompromised due
      to infection with the human immunodeficiency virus (HIV), and who subsequently
      developed acute mastoiditis due to Aspergillus fumigatus. Fungal otomastoiditis
      is a rarely reported complication of HIV infection. A high index of suspicion is
      required in these patients to facilitate early diagnosis and appropriate therapy.

PMID- 9231093
TI  - Reversible sensorineural hearing loss in Lyme disease.
AB  - We report a case of bilateral sensorineural hearing loss of two years duration
      which appears to have been due to late Borrelia burgdorferi infection. The 39
      year-old woman presented with bilateral deafness and multiple other neurological
      complaints some six months after developing a 'target' lesion on the lower leg
      after walking in the New Forest. 'Serology' for Borrelia burgdorferi became
      positive and the patient made a complete recovery from both her deafness and her
      other neurological problems after a five-week course of oral antibiotic therapy.

PMID- 9231094
TI  - Ectopic pituitary adenoma in the sphenoid causing Nelson's syndrome.
AB  - An ectopic functioning pituitary in the sphenoid is an extremely rare occurrence,
      and even rarer is pituitary adenoma causing symptoms of Nelson's syndrome. A case
      is presented of a young female diagnosed and treated in our clinic. The only
      functioning hypophyseal tissue was detected inside the sphenoid, as the pituitary
      gland had been radiated because of Cushing's syndrome 10 years before and imaging
      studies revealed an empty sella.

PMID- 9231095
TI  - Laryngeal inflammation mimicking laryngeal carcinoma.
AB  - A case of severe inflammation with an exuberant granulation lesion of the larynx
      that mimicked laryngeal tumour is presented. A patient who was a chronic smoker,
      with a history of hoarse voice underwent multiple endoscopies and biopsies,
      confirmed histopathologically as acute and, subsequently, as chronic
      inflammation. The tumour-like tissue in the larynx responded dramatically to
      prolonged antibiotic treatment. We emphasize the importance of histological
      confirmation before embarking on removal of an essential organ or part of the
      body which could lead to physical or emotional scarring.

PMID- 9231096
TI  - Primary non-Hodgkin's lymphoma of the larynx.
AB  - Three cases of primary non-Hodgkin's lymphoma of the larynx are described.
      Histologically, two tumours belonged to the category of low grade B-cell
      lymphomas of the small cell type (extranodal marginal zone B-cell lymphoma and
      lymphoplasmacytoid lymphoma), and the third was classified as a peripheral T-cell
      lymphoma of unspecified type. The clinical stage was IE in two cases, and IV in
      another case. In two cases, complete remission was obtained with radical
      radiotherapy. But in the other case, which was histologically lymphoplasmacytoid
      lymphoma, the response to radiotherapy was poor, and surgery was required. There
      was no relapse subsequent to treatment. Primary non-Hodgkin's lymphoma of the
      larynx is rare. Several reported cases have clinical features similar to those of
      MALT-type lymphomas arising in other extranodal sites. Although most of the
      reported cases have been cured with radiotherapy, in some cases dissemination to
      other extranodal sites may occur. Therefore careful periodic evaluation is
      imperative.

PMID- 9231097
TI  - An unusual case of laryngeal carcinoma metastasizing to the small intestine.
AB  - An unusual case of laryngeal carcinoma metastasizing to the small intestine is
      reported. The patient was admitted to our hospital due to hoarseness, sore throat
      and dyspnoea. Pathological examination on the laryngeal mass revealed it to be
      moderately differentiated squamous cell carcinoma, staged as T4N0M0. A total
      laryngectomy and right modified neck dissection were performed. Over two years
      after the operation a small intestinal tumour was found, with a resultant
      resection of the ileum and sigmoid colon. An infiltration of the cell nests of
      squamous cell carcinoma were present at the submucosal regions of the ileum.
      These findings indicated that the laryngeal cancer had already metastasized to
      the small intestine at the time of the initial treatment.

PMID- 9231098
TI  - Parapharyngeal abscess: a rare complication of elective tonsillectomy.
AB  - We report a case of parapharyngeal abscess complicating an elective tonsillectomy
      in a healthy thirty-three-year-old woman. The clinical features and management of
      this very rare complication are discussed. In addition, we review the possible
      aetiology and pathogenesis of this potentially life-threatening condition.

PMID- 9231099
TI  - Simultaneous occurrence of metastatic tonsillar squamous cell carcinoma and
      angioimmunoblastic T-cell lymphoma in a cervical lymph node.
AB  - Non-Hodgkin's lymphoma (NHL) is a frequent head and neck malignancy. Squamous
      cell carcinoma of the tonsil is the second most common head and neck carcinoma.
      We report a case of a tonsillar carcinoma metastasis in an angioimmunoblastic
      transformedlymph node. To our knowledge this is the first description and
      histopathological documentation of such a case in the literature.

PMID- 9231100
TI  - Combined forceps and catheter extraction of an oesophageal foreign body.
AB  - The extraction of impacted foreign bodies from the oesophagus is frequently
      performed using forceps under endoscopic guidance. We report the case of a 23
      year-old prisoner who ingested a lump of cannabis resin which could not be
      removed from the upper oesophagus with forceps alone. We recommend the use of a
      Fogarty balloon catheter in conjunction with toothed forceps in such cases.

PMID- 9231101
TI  - Extracapsular haemorrhage from a parathyroid adenoma presenting as a massive
      cervical haematoma.
AB  - Spontaneous massive haemorrhage from a parathyroid adenoma is rare. It can cause
      extensive cervical ecchymosis as well as compression of structures within the
      neck. We present a case, discuss the diagnostic features and review the
      literature.

PMID- 9231102
TI  - Capillary haemangioma of the parotid in an adult: an unusual case and a review of
      the literature.
AB  - Haemangioma of the parotid gland is a well-described condition that accounts for
      50 per cent of parotid tumours presenting during the first year of life. Parotid
      haemangiomas in adults are much rarer and until now only the cavernous variety
      have been reported. We report a case of a capillary haemangioma in an adult and
      discuss the literature.

PMID- 9231103
TI  - Cavernous lymphangioma in the adult parotid.
AB  - Cavernous lymphangioma is a benign congenital lesion that usually appears in
      childhood. It rarely presents in the adult but may be diagnosed at this late
      stage due to the slow growing nature of the tumour. It is rarely found in the
      salivary glands and when it does occur, the gland is usually incorporated by
      lymphangioma of surrounding tissue. We present and discuss the case of a
      cavernous lymphangioma in the parotid gland of an adult male.

PMID- 9231104
TI  - The surgical treatment of snoring.

PMID- 9231105
TI  - Homage: Steven Abrahamson.

PMID- 9231107
TI  - Videotaped interviewing of non-English speakers: training for medical students
      with volunteer clients.
AB  - In a multicultural society such as Australia, with over 20% of its population
      born overseas, interpreters are often required to facilitate medical interviews.
      However, where a patient has some proficiency in English, medical interviews are
      sometimes conducted across the boundaries of culture and language. This is a
      report of an educational innovation to teach interviewing skills to pre-clinical
      medical students with the assistance of volunteers of non-English-speaking
      backgrounds. Pre-clinical students interviewed community volunteers on topics of
      general life history in a sequence of 16 tutorials. Each student conducted two
      interviews. Teaching methods included feedback from the volunteers, tutorial
      discussion facilitated by playback of videotapes, and modelling of skills by the
      teachers. Evaluations by volunteers and students indicated high satisfaction with
      the teaching methods and outcomes. Students gained confidence in interviewing
      people from different cultures. Evaluation of students' pairs of videotapes by an
      independent rater achieved satisfactory reliabilities and indicated significant
      gains in inquiry skills and the communication of positive attitudes. Skills in
      communicating empathy and in using simple language did not improve measurably.

PMID- 9231106
TI  - Language as a barrier to the acquisition of anatomical knowledge.
AB  - The language of instruction for medical students at the University of Hong Kong
      is English, which is their second language. This presents a potential barrier to
      their academic learning. We have studied the extent of this problem by looking at
      the amount of terminology students have to assimilate during their anatomy course
      and the way in which the terminology is structured and explained (this provides,
      more generally, an indication of the factual loading to which medical students
      are exposed). We have also investigated the effect of the quality of students'
      language skills on their examination results in anatomy class tests and MBBS
      exams. It was found that students' entrance levels in English correlated well
      with their final examination results and that the quality and quantity of their
      English also correlated highly with scores in class tests. On this basis, we
      conclude that language is one of the most important barriers to students'
      academic success in the department and that current teaching materials may not be
      appropriate.

PMID- 9231108
TI  - Audit in general practice: educating medical students.
AB  - This paper describes the third stage in the evolution of methods of teaching on
      audit in general practice at the Department of General Practice, University of
      Glasgow. The authors asked the final year students to develop, carry out and
      submit a written report on an audit project devised by themselves, after briefing
      and with continued support. Every student asked was successful in producing a
      report and the standard was generally very high, although only two students
      completed the audit cycle in the 4 week period. More than half the students
      (51.7%) found the project valuable or very valuable. As many as 90.6% understood
      audit better or much better after doing the project and 83.4% thought that the
      project should continue to be part of the GP attachment. Seventy-eight per cent
      of the GP tutors thought that teaching audit to undergraduates in general
      practice was valuable or very valuable, 64.4% reported that the audit had been of
      benefit to their practice, and 89.9% thought that audit should continue to be
      part of the GP attachment. This method of teaching students about audit was the
      most successful of three methods tried. It has produced benefits both for
      students and for the general practices to which they were attached, ultimately
      producing benefits for patients.

PMID- 9231109
TI  - Does knowledge of drug prescribing predict drug management of standardized
      patients in office practice?
AB  - Drug prescribing for the elderly is an important area of medical knowledge since
      inappropriate prescribing may lead to significant adverse drug events. The
      objective of this study was to evaluate the association between knowledge of drug
      use and quality of drug management by general practitioners in practice. A cross
      sectional study design was used to evaluate a sample of 37 GPs in practice. A set
      of common musculoskeletal problems was chosen to evaluate doctors' knowledge of
      non-steroidal anti-inflammatory drug use, while performance in practice was
      assessed using elderly standardized patients. The reliability of knowledge test
      scores was evaluated using measures of internal consistency. The relationship
      between knowledge of drug use and quality of therapeutic management in practice
      was evaluated by rank order and linear correlation analysis. Demographic
      characteristics of participating and non-participating doctors were similar. The
      reliability of the knowledge test was 0.55. The reliability of performance scores
      was 0.66. The correlation between overall performance on the standardized patient
      cases and total knowledge test score was 0.22 (95% confidence interval = 0-0.63).
      Knowledge test scores were poorly correlated with quality of therapeutic
      management in office practice. This indicates that knowledge tests alone cannot
      predict quality of performance with regard to drug prescribing for the elderly in
      primary care office practice.

PMID- 9231110
TI  - The workload of trainees in general practice.
AB  - During their first training period in general practice the authors felt that they
      did not encounter the balanced workload which is the foundation for learning to
      be a GP. Previous studies confirmed the existence of differences in overall and
      specific workload between trainees and trainers. From their own experience and
      from the relevant literature they addressed several factors which might affect
      the workload of trainees. A study was undertaken to determine differences in
      workload between trainees and trainers, and to investigate whether certain
      characteristics of practice and of trainees affect the workload of trainees.
      Details of surgery consultations with 34 trainee-trainer partnerships were
      recorded in the north of the Netherlands over 2 weeks. Questionnaires were filled
      in by trainers, trainees and practice assistants from these 34 general practices.
      The total number of contacts recorded was 10,103. It was found that trainees see
      fewer elderly and female patients, less chronic and oncological conditions, but
      more minor illnesses. They see only 30% of patients with problem behavior.
      Factors that influence the trainees' workload, as compared to their trainers'
      are: list size; selection in the allocation of patients; trainee's experience
      prior to starting the training stage, and the trainee's sex. Except for problem
      behaviour, trainees generally see a cross-section of their trainer's practice
      population. Selection would provide a more balanced workload for trainees.

PMID- 9231112
TI  - Acquisition of basic clinical skills in the general practice setting.
AB  - Undergraduate medical education in the UK is changing due to both education
      pressure (from the General Medical Council) and changes in the hospital service.
      As a result the role of general practice in providing core clinical experience is
      under debate. The purpose of this study was to determine the clinical contact
      available for junior clinical medical clerks (third year) attached to five
      general practices. We report here on the clinical experience recorded by students
      during 106 sessions (74% of possible sessions). One hundred and one patients were
      seen, 54% females; ages ranging from 14 to 92. Four hundred and twenty-six
      symptoms were recorded; the largest category (36%) was CVS/respiratory followed
      by neurological (20%). Shortness of breath was the commonest single symptom (46%
      in the CVS/respiratory category). Three hundred and seventy-one signs were
      recorded; 48% were in the CVS/respiratory category, 33% in the neurological
      category. Cardiac murmurs were the commonest single sign (34% of the
      CVS/respiratory category). Sixty-nine separate comments were made by students
      about the range of clinical experience available; all were favourable. Forty
      eight per cent of comments highlighted the availability of patients with
      appropriate symptoms and signs. This study has demonstrated that general
      practices can provide appropriate clinical exposure which complements hospital
      teaching for junior students.

PMID- 9231111
TI  - Clinical skills assessment with standardized patients.
AB  - Previous projects (Combell I & II) to assess clinical skills were conducted in
      medical schools in Catalonia, in order to introduce a model of such an assessment
      using standardized patients (SP). The aim of this study (Combell III) was to
      measure selected characteristics of our model. Seventy-three medical students in
      the final year at the Bellvitge teaching unit of the University of Barcelona
      participated in a clinical skills assessment (CSA) project that used 10 SP cases.
      The mean group scores for the four components of clinical skills for each day of
      testing were studied, and ratings for each student in the 10 sequential
      encounters were checked. The study also compared the clinical skills scores with
      their academic grades. The total case mean score (mean score of history-taking,
      physical examination and patient notes scores) was 51.9%, and the mean score for
      communication skills was 63.6%. The clinical skills scores over the 8 testing
      days showed no day-to-day differences. The study did not find differences among
      the sequential encounters for each student (training effect). There was a lack of
      correlation between clinical skills scores and academic grades. The project
      demonstrated the feasibility of the method for assessing clinical skills,
      confirmed its reliability, and showed that there is no correlation between scores
      with this method and academic examinations that mainly reflect knowledge.

PMID- 9231113
TI  - Teaching and learning in day surgery units: a UK survey.
AB  - Recent increases in day case surgery offer new opportunities for medical student
      learning, whilst the reduction in surgical beds and length of hospital stays has
      reduced opportunities in traditional inpatient settings. To establish the extent
      and nature of undergraduate medical education in day surgery units in the UK, the
      authors undertook a postal questionnaire survey. Of the 227 units which replied,
      45% are used for teaching. In 83% of these, students attend only single operating
      lists, and only 7% of units take students for more than 1 day per week. This
      suggests that students have very limited teaching in day surgery units.
      Diagnosis, common surgical procedures and rehabilitation are increasingly carried
      out in outpatient, day case and community settings. These may be missed by
      students unless educational programmes are responsive to trends in health care
      delivery. Day surgery units could play an increased role in medical education.

PMID- 9231114
TI  - Curriculum change: the importance of team role.
AB  - This paper describes a study examining aspects of team role in the management of
      curriculum change. The Belbin Team Role Self-Perception Inventory was completed
      by 25 members (83%) of a faculty curriculum development team. Overall the group
      showed a preference for the implementer and shaper roles, whilst the completer
      finisher role was relatively weakly represented, ranking fifth out of eight
      possible roles. Older and more senior team members favoured the co-ordinator
      role, whilst younger and more junior members favoured the team-worker and
      completer-finisher roles. Some implications of these findings are discussed in
      the light of the current trend for widespread change in undergraduate medical
      curricula and the challenges faced by medical schools in a resource constrained
      environment.

PMID- 9231116
TI  - Interviewing skills: self-evaluation by medical students.
AB  - In an independent learning project, 52 third-year medical students carried out a
      structured self-assessment of two videotaped psycho-social interviews they had
      conducted with volunteer clients 1 year earlier, as part of a previous course.
      The interviews had been conducted in small tutorials with feedback from their
      clients, fellow students and tutors, facilitated by videotape playback. During
      the sequence of 16 tutorials each student had carried out an early and a late
      interview and had observed and participated in the discussion of the interviews
      of 14 peers. Students were asked to tally the frequencies of various interview
      behaviours, to evaluate the quality of their behaviours, and to establish
      priorities for future learning. The videotapes were also reliably rated by an
      independent observer. Students' overall self-assessments correlated 0.46 with
      those of the independent observer. This correlation was higher than is typically
      reported in studies of the validity of self-assessment. In absolute terms, the
      students' mean rating of interviewing performance was 3.2 (adequate plus) which
      was significantly lower than the observer's mean of 3.6 (adequate to good).
      Results are discussed in terms of Gordon's (1992) two recommendations for
      improving the validity of self-assessments and two further suggestions, for
      paired comparisons and low-threat learning environments, are added.

PMID- 9231115
TI  - Measuring knowledge and clinical reasoning skills in a problem-based curriculum.
AB  - The purpose of this study was to investigate the validity of the Progress Test
      that was specially designed for measuring the growth of knowledge and clinical
      reasoning skills in a problem-based medical curriculum. Scores and subscores of
      students from the different categories of the Progress Test were compared with
      their scores on a Clinical Reasoning Tests. Both the Progress Test and the
      Clinical Reasoning Test revealed the same pattern of increasing scores over the
      years, and had a high intercorrelation. Further analyses revealed that the
      clinical sciences subscore in the progress test explained the variations in the
      clinical reasoning test scores. The knowledge of the behavioural sciences
      subscore made a small but independent contribution. The knowledge of the
      biomedical sciences subscore did not have this independent effect. These outcomes
      are discussed in this paper from the perspective of development of medical
      expertise research and theory. Some educational consequences are also discussed.

PMID- 9231117
TI  - Postgraduate training. Policy paper prepared by the Subcommittee on Postgraduate
      training: Permanent Working Group of European Junior Hospital Doctors.
AB  - The Permanent Working Group of European Junior Hospital Doctors (PWG) represents
      the interests, in international matters, of trainees from 23 member states. The
      PWG recognizes the importance of postgraduate training (PGT) in the maintenance
      of high quality health care delivery, and in this paper presents its current
      policy on PGT. This replaces its policy previously published in Medical Education
      1989, 23, 339-47. The paper examines the context within which PGT occurs, and
      calls for an urgent review of its provision and funding. Basic principles, such
      as PGT existing within a continuum of medical education and the application of a
      quality assurance-based model, underpin the development of later sections on the
      structure, process and outcomes of PGT. These recommend the establishment of
      structured training programmes which should incorporate modern educational
      practice in the provision and monitoring of PGT. Emphasis is placed on the
      opportunities for training in the clinical setting and the utilization of a range
      of educational techniques. Evaluation and guidance by and of clinical supervisors
      and designated trainers is linked with the responsibilities of the trainee, and
      is placed within the context of a system of accountability, thus closing the
      quality assurance cycle. It is recommended that the views of the consumers of
      PGT, the trainees, are more fully considered in the development of training
      programmes. Finally, the potential for further harmonization is considered, with
      cautious advances being proposed.

PMID- 9231118
TI  - Training experiences immediately after medical school.
AB  - Trainees in all teaching hospitals in New South Wales were surveyed using a self
      completion, postal questionnaire to assess perceptions of the quality and extent
      of training received for interactional and technical skills. The response rate
      was 67.1%. Mean age was 25.4 years and 38.8% were female. Overall, training was
      found to be generally poor in terms of time and educational strategies used.
      Interactional skills were found to receive lower levels of training than
      technical skills both prior to and during the intern year with significantly
      fewer (P < 0.000) educational strategies reported for training received in
      interactional skills than for technical skills. Trainees' perceptions of the
      adequacy of training was significantly more negative for interactional than
      technical skills (P < 0.001). Assessment of competence was also significantly
      lower for interactional than technical skills (P < 0.001). On average, fewer than
      one in three trainees considered themselves to be competent in interactional
      skills compared to two-thirds who reported themselves as competent for technical
      skills. The findings of this study highlight the need for improved efforts with
      regard to both the quality and quantity of training provided during the intern
      year. Considerable scope exists for improved educational experiences for both
      interactional and technical skill areas, but particularly for interactional
      skills. Overall, greater use of a range of basic educational strategies such as
      the provision of 'observation' and 'critical feedback' is indicated. Efforts also
      need to be directed toward the training of clinical educators to optimize the
      potential of the preregistration period.

PMID- 9231119
TI  - Doctor-patient communication: a study of junior house officers.
AB  - This study evaluates junior house officers' perceptions of their communication
      skills with cancer patients; the usefulness of their undergraduate communication
      skills training; and their sources of emotional support. All 42 junior house
      officers employed at Guy's and Lewisham Hospitals in August 1994 were interviewed
      using a study-specific, semi-structured interview. Sixty-seven per cent of junior
      house officers felt they had adequate communication skills in relation to medical
      issues, but only 36% felt they had adequate skills in relation to psychological
      issues. Thirty-one per cent of doctors reported that they never, or nearly never,
      enquired about the emotional adjustment of dying patients. Lack of time was the
      most commonly reported reason for avoiding asking about psychological problems
      (62% of junior house officers), followed by wishing to avoid awkward questions
      (51%) and inadequacy of skills to deal with such issues (44%). Ninety-eight per
      cent of junior house officers had attended the 1-week undergraduate communication
      skills course at Guy's and St Thomas's Hospital Medical School (UMDS). Sixty
      seven per cent of those who had attended found the course helpful and 62% felt
      they would benefit from further training as junior house officers. Seventy-four
      per cent felt they could discuss their work-related concerns with colleagues and
      95% felt they could talk to friends. In contrast only about 9% felt they could,
      if needed, talk to a counsellor. Although the majority of the junior house
      officers reported benefit from their communication skills training, the course
      does not appear to be meeting all their communication training needs. Junior
      house officers require further training opportunities at the undergraduate and
      postgraduate levels. Traditional counselling services for junior house officers
      may not be meeting their support needs.

PMID- 9231121
TI  - Rewards for teaching excellence: practice in South African medical schools.
AB  - Excellence in teaching through recruitment of good teachers, rewarding good
      teaching and the creation of staff development programmes are priorities in the
      mission statement of most universities. Often, reality belies intention. At many
      universities serious attempts to ensure maximum teacher effectiveness, overt
      recognition of teaching excellence, and specific development funding are lacking.
      This study examines the extrinsic (i.e. financial) reward systems which operate
      at the eight medical schools attached to South African universities and reports
      on the current situation. Replies indicated that a reward system of some type
      operates within the university at seven South African universities which have
      faculties of medicine and embraces all faculties. One university rewards medical
      school teachers specifically but, at another, no reward system exists at all. The
      monetary value of rewards varies greatly. Significant criticism of all systems
      was the inability to meet their design aims. There was criticism of the criteria,
      such as they are and where they exist, used to identify teaching excellence and
      to reward recipients. All replies indicated support for an impartial and
      equitable system of reward for effectiveness and excellence in teaching.

PMID- 9231120
TI  - Portfolio-based learning: continuing medical education for general practitioners-
      a mid-point evaluation.
AB  - In October 1994 a project was initiated by the General Practice Continuing
      Medical Education Tutors in the Department of General Practice at Sheffield
      University. The project sought to evaluate the efficiency (effort expended) and
      effectiveness (distance travelled) of a model of continuing professional
      development for general practitioners through individual portfolio-based learning
      in co-mentoring groups. Learning demonstrated through the portfolio was
      accredited for the postgraduate education allowance of participants. This paper
      addresses the process of portfolio development at the mid-point of a year-long
      trial to ascertain the strengths, weaknesses and possible future development of
      such a process within the context of continuing medical education.

PMID- 9231122
TI  - Teaching and assessing clinical skills: a competency-based programme in China.
AB  - The objective of this study was to develop a competency-based clinical skills
      teaching and assessment programme in China utilizing modern teaching techniques.
      Medical teachers from three schools agreed on items for inclusion in the complete
      physical examination of an asymptomatic adult, an outline for an adult and
      paediatric history, and important interviewing skills. Lesson plans, performance
      checklists, and written and videotape training materials were developed.
      Standardized patients were trained at one school to assist with the teaching at
      that school and with the assessment at all three schools. A national, a
      provincial, and a local medical school in China were used. Before beginning the
      new curriculum for students in their first year of clinical training, baseline
      data were collected on skills of students at various levels of training in the
      previous curriculum at all three schools. Although in the previous curriculum
      there was some improvement in clinical skills among advanced compared to more
      junior students, performance was lower than expected by staff. One year after
      implementation of the new curriculum, students were evaluated. These students
      significantly outperformed their counterparts as well as the more senior level
      students tested the previous year. This project has established a competency
      based teaching and assessment programme in China that allows for rapid
      improvement in the clinical skills of students. Within a short time, a
      sophisticated group of medical educators has been formed, who now function as
      consultants to other educators in their own country. Many aspects of this
      programme are being adapted throughout China and are applicable to medical
      schools throughout the world.

PMID- 9231123
TI  - Student identification of ethical issues in a primary care setting.
AB  - Ethical issues in the clinical arena have received significant attention during
      the past few decades. Limited focus has been directed toward ethical issues in
      the primary care office setting. A study was conducted to determine the ethical
      perspectives through critical review discussions between medical students and
      their preceptors during the PCP programme. Major ethical themes and percent of
      occurrence emerging from an analysis of the summaries of their discussions
      included decision-making (40%), professional standards (16%), locus of care
      (12%), community responsibility (10%), and confidentiality (10%). This study adds
      to the evidence that while the ethical issues prevalent in the primary care
      setting are less dramatic than those in a hospital, they are sufficiently
      frequent to warrant inclusion in the curriculum, enabling students to become more
      sensitive to their existence.

PMID- 9231125
TI  - Special study modules: an opportunity not to be missed.
AB  - The General Medical Council's (GMC's) Tomorrow's Doctors has proposed a radical
      rethink of undergraduate medical education. The two main planks of the proposals
      are the core curriculum and special study modules (SSMs) or options. Medical
      schools around the country have been much exercised in creating their core
      curricula but there has been less time given to a consideration of the SSMs. This
      paper looks at the GMC's proposals for SSMs and emphasizes their importance in
      introducing innovation and originality. Three different categories of SSM are
      described and a justification made for including each in the curriculum. The
      focus is on what non-medical subjects might contribute to medical education.

PMID- 9231124
TI  - The Medical Skills Centre at the University of Calgary Medical School.
AB  - The aim of the Medical Skills Centre at the University of Calgary is to provide a
      predictable learning environment and standardized teaching methods in the area of
      clinical skills teaching. The centre uses volunteer patients and trained actors
      for all levels of medical education and evaluation. A computer database enables
      easy access to groups of patients and varying medical issues. This article
      describes the organization and operation of the Medical Skills Centre and notes a
      variety of courses which use the unique facilities of the centre.

PMID- 9231126
TI  - Effective teaching of communication skills for medical practice: selecting an
      appropriate clinical context.
AB  - Increasingly, courses in communication skills are being incorporated into medical
      training. In order for communication skills to be effectively maintained in post
      training medical practice, they must be taught within an appropriate clinical
      context. The present paper describes and provides rationale for seven criteria by
      which to select clinical issues which are appropriate foci for communication
      skills courses. The criteria are: (1) the issue must be one which is encountered
      frequently in clinical practice; (2) the issue must be associated with a high
      burden of illness; (3) there must be evidence that practitioners need to improve
      skills for dealing with the issue; (4) there must be an intervention, of which
      communication skills are an integral component, that is demonstrably effective
      for dealing with the clinical issue; (5) the intervention must represent a cost
      effective means of dealing with the issue; (6) the intervention must be
      acceptable to doctors and be able to be incorporated into routine medical
      practice; (7) the intervention must be acceptable to patients. Examples of
      clinical issues which fit these criteria are given in the paper and include
      smoking, hazardous alcohol consumption, non-adherence to treatment instructions,
      overdue cervical screening, inappropriate diet, recovery from medical
      interventions, and breaking bad news to patients.

PMID- 9231128
TI  - Continuing medical education: the question of evaluation.
AB  - This paper examines the question of evaluation which has been largely neglected
      in the credit-based systems of continuing medical education adopted by the
      Medical Royal Colleges. These systems are seen to encourage a training model of
      continuing education and a scientific model of evaluation as measurement. By
      contrast, humanistic evaluation is interpretative and differs not only in its
      criteria and methods, but also in its underpinning curricular ideologies and
      values. This model has closer links with concepts of education and professional
      practice associated with continuing professional development. Decisions about who
      should conduct the evaluation, what is to be evaluated, how it should be carried
      out, and about the goals and purposes of evaluation are outlined, noting that
      they presuppose an ideological view of the relationship of professional
      knowledge, values and practice. In a concluding discussion of evaluation and the
      control of professional knowledge, it is argued that the narrow, professional
      control of evaluation, buttressed by the quality assurance and monitoring
      mechanisms of the Colleges, is inappropriate, given the increasingly diverse
      accountabilities which affect medical professionals.

PMID- 9231127
TI  - Cultural diversity in Australian medical education.
AB  - The present study sought to explore the relevance of cultural dimensions and
      cultural diversity among overseas and local medical students. The main comparison
      among the fourth year medical students studied was between Asian origin and
      Anglophone background students. The measures used included cultural variation,
      reasons for studying medicine, learning approaches and strategies, patient
      interaction confidence, and medical practices anxieties. Results indicated
      cultural differences between the two groups, and relationships between cultural
      variables and, in particular, reasons for studying medicine, learning approaches
      and strategies, and patient interaction confidence. Results were interpreted
      according to Hofstede's (1980, 1986) theory of cultural dimensions as they may
      apply in the educational setting.

PMID- 9231130
TI  - Medical schools without walls.

PMID- 9231129
TI  - Certification of specialists: the Portuguese system and future relation to
      European Boards.

PMID- 9231131
TI  - The reform of medical education in Iran.
AB  - In order to investigate the path of medical education in Iran, indicators of
      medical education were searched from 1970 to 1994. There have been rises in the
      number of educational institutions from 10 to 46; student admissions in
      programmes of medical sciences from 1387 to 18,141; medical student admissions
      from 632 to 3630; teaching staff from 1573 to 7979; and teaching-bed to student
      ratio from 1.05 to 2.08. The numbers of students in clinical specialty and MS
      degrees have increased, and various programmes in clinical sub-specialty and PhD
      degrees have been initiated. The quality of medical education has improved with
      increasing field and ambulatory care training, with more emphasis on teaching
      preventive medicine and a significant rise in the research activities. Most
      qualitative and quantitative progress has been achieved following the
      establishment of a joint Ministry of Health and Medical Education in 1985. The
      results of this review demonstrate the success of Iran in upgrading medical
      education by the unification of health services and medical education in one
      ministry.

PMID- 9231132
TI  - Predicting stress in first year medical students: a longitudinal study.
AB  - While there is ample documentation that medical training is stressful, less is
      known about predictive variables that might identify students who have the most
      difficulty in managing stress during medical training. Depression and anxiety in
      first year medical students were investigated in a longitudinal design. One
      hundred and twenty-one medical students (81% of the class) were surveyed. The
      first survey took place immediately prior to the beginning of medical training
      (wave 1); the second survey was approximately 8 months after the beginning of
      classes (wave 2). Medical students who began their first year with relatively low
      'A' level grades, high ratings of state anxiety and depression, high trait
      anxiety and low dispositional optimism, and reliance on avoidant coping
      strategies were found to be at higher risk for developing depression and anxiety
      symptoms at wave 2. Students reported increased concern about curriculum and
      environment, personal competence and endurance, and time to have a life outside
      medical school at wave 2, compared to their reports at wave 1. Increase in
      concerns correlated with an increase in depression and anxiety. At both surveys,
      use of avoidant coping strategies resulted in increased depression and anxiety;
      at wave 2, active coping and positive reinterpretation resulted in decreased
      depression and anxiety. These findings suggest characteristics of vulnerable
      students who might be identified early in their first year and provided with
      additional support. Educating students to expect an increase in concerns about
      environment and personal ability to manage the academic load might make these
      concerns less overwhelming. In addition, information about effective coping
      strategies (i.e. active coping efforts) and ineffective means of dealing with
      stress (avoidant coping efforts) might be helpful in preventing distress.

PMID- 9231133
TI  - Smoking behaviour and attitudes among Australian medical students.
AB  - Teaching about tobacco and related diseases is essential in the undergraduate
      medical course in order for students to gain knowledge about smoking and how to
      intervene with patients who smoke. The objective of the study was to assess
      students' smoking-related behaviour, knowledge and attitudes towards tobacco, and
      perceptions of their future role as doctors. Data were collected from two
      consecutive years of year 1 and year 5 medical students at the University of New
      South Wales, Sydney. A total of 594 (79%) of students across the 2 years
      completed the survey: 90% of year 1 students, and 69% of year 5 students. The
      daily smoking rate among the total medical students was 2.9%: 11.8% in year 1
      (2.3% daily, 9.5% occasional) and 13.7% in year 5 (3.3% daily, 10.4% occasional).
      There were significantly more male than female smokers in year 5 (P < 0.05). The
      overall smoking rates for males in years 1 and 5 were 12.4% and 19.3%, and the
      smoking rates for females were 11.2% and 8%. Knowledge about the causal role of
      tobacco in the development of specific diseases improved significantly from year
      1 to year 5 (P < 0.001). Nevertheless, in year 5 there remained a lack of
      knowledge about the relationship of smoking and some diseases. Fifty-seven per
      cent of students thought that their current knowledge was sufficient to counsel
      smokers, with year 5 students (89%) being far more positive than year 1 students
      (34%) (P < 0.001). Teaching medical students about smoking-related diseases and a
      patient-centred smoking cessation intervention results in an increase in
      knowledge, as well as positive perceptions about their future role in intervening
      with smokers.

PMID- 9231134
TI  - Basic sciences in problem-based learning and conventional curricula: students'
      attitudes.
AB  - The purpose of this study was to compare the attitudes toward basic sciences of
      students in a preclinical problem-based curriculum and a conventional lecture
      based curriculum at the end of their second year of medical school. The results
      showed that the PBL class had more positive attitudes toward basic sciences than
      students in the conventional class. These results may reflect a learning
      environment where students meet many scientist role models as teachers and where
      basic science is learnt in the context of clinical problems.

PMID- 9231135
TI  - Teaching of medical ethics: implications for an integrated curriculum.
AB  - This paper reports on an investigation into the teaching of medical ethics and
      related areas in the medical undergraduate course at the University of
      Queensland. The project was designed in the context of a major curriculum change
      to replace the current 6 year course by an integrated, problem-based, 4 year
      graduate medical course, which began in 1997. A survey of clinical students,
      observations of clinical teaching sessions, and interviews with clinical teachers
      were conducted. Data obtained have contributed to curriculum development and will
      provide a baseline for comparison and evaluation of the graduate course in this
      field. A view of integrated ethics teaching is advanced in the light of the data
      obtained.

PMID- 9231136
TI  - Skills of pre-registration house officers: gender differences reported in Norway.
AB  - During training pre-registration house officers should acquire skills, practical
      clinical procedures, and good clinical judgement, in order to be able to practice
      on their own. This is not always the case (Flaatten et al. 1987). Ten years ago
      the Norwegian Health Authorities issued a regulation regarding the content of
      hospital training (6 months internal medicine and surgery, respectively). A
      number of practical skills to be learned were listed. As part of an assessment of
      the quality of the internship, a study was carried out into what extent the pre
      registration house officers had acquired these clinical skills.

PMID- 9231137
TI  - Student feedback: influencing the quality of teaching in a paediatric module.
AB  - The aim of this study was to assess the impact of feedback on the quality of
      tutorials. Students completed structured feedback questionnaires on the perceived
      usefulness of teaching sessions. They perceived significant differences in the
      quality of tutorials delivered by experienced and inexperienced teachers (P <
      0.01), although the differences tended to become less throughout the year. In the
      second year, teachers had advice from an experienced tutor in planning the
      sessions, in addition to receiving feedback from the students. During the second
      year, the students did not perceive any difference in the usefulness of these
      tutorials to them. The study showed that the quality of tutorials can be improved
      by passing structured feedback to the teacher, but that some skills training was
      also required to completely eliminate perceived differences.

PMID- 9231138
TI  - Pelvic manikins as learning aids.
AB  - The use of pelvic trainers in undergraduate teaching was evaluated, using a
      questionnaire based on examination findings of a series of four pelvic trainers
      by 20 medical students and 34 gynaecologists. The main outcome measures were the
      ability to correctly identify pelvic findings in the trainers, and the numbers of
      false positive findings. There were two adnexal masses in two of the trainers.
      One was correctly identified by 33 (14 (70%) medical students and 19 (56%)
      doctors) in one trainer, whereas the other was missed by 52 of 54 examiners.
      Prolapse was missed by 41 of 54. The normal pelvis was correctly identified by 30
      (16 (80%) medical students and 20 (59%) doctors. There were 15 false positive
      identifications of adnexal masses (6 by medical students and 9 by doctors) and 22
      false positive identification of uterine enlargements (5 by medical students and
      17 by doctors). The pelvic trainers were of value in demonstrating the process of
      pelvic and speculum examination. Some of the clinical conditions emulated were
      missed by most of the gynaecologists, suggesting that they were not suitable for
      training students in abnormal findings. Although the figures were not
      statistically significant, there was a trend for qualified doctors rather than
      medical students to make false positive findings.

PMID- 9231139
TI  - Computer-based learning materials for medical education: a model production.
AB  - Computer-based learning materials (CBL or courseware) have the potential to be
      valuable learning resources for medical education. However, CBL has failed to
      realize its potential primarily because of unstructured approaches towards design
      and development. This paper describes the courseware development model (CDM), a
      conceptual model produced and used by the Medical Education Unit at The
      University of Liverpool. The model describes a structured multi-disciplinary
      approach to the design and production of CBL materials. It promotes meticulous
      planning, communication and organization. The CDM draws on three areas of
      expertise: (1) education; (2) computer science; and (3) medical content.

PMID- 9231140
TI  - Kabisa: an interactive computer-assisted training program for tropical diseases.
AB  - In Europe, tropical pathology is usually taught in special short courses,
      intended for those planning to practise in developing countries. The theoretical
      knowledge to be assimilated during this short period is considerable, and turning
      such newly acquired knowledge into competence is difficult. Kabisa is a computer
      based training program for tropical diseases. Instead of concentrating on
      strictly tropical diseases, students are trained in recognizing diseases in
      patients presenting randomly in an imaginary reference hospital in a developing
      country. Databases are compiled by experts from experiences in various parts of
      Africa, Asia and tropical America. Seven languages and three levels of competence
      can be chosen by the student. Updating of all databases is possible by teachers
      who want to describe a particular setting. A 'consistency checker' verifies the
      internal consistency of a new configuration. The logical engine is based upon
      both a 'cluster' and a Bayesian logic, with built-in corrections for related
      disease characteristics. This correction allows calculated probabilities to stay
      closer to real probabilities, and avoids the 'probability overshoot' that is
      inherent to 'idiot Bayes' calculations. The program provides training in
      diagnostic skills in an imaginary second-line setting in a tropical country. It
      puts tropical and cosmopolitan diseases in perspective and combines applied
      clinical epidemiology and pattern recognition within varying sets of presenting
      symptoms. Students are guided in searching for the most relevant disease
      characteristics, in ranking disease probability, and in deciding when to stop
      investigating.

PMID- 9231141
TI  - A regionalized perinatal continuing education programme: successful adaptation to
      a foreign health care system and language.
AB  - Much of the decline in perinatal mortality over the past two decades in the
      United States has been attributed to regionalization of perinatal care. Outreach
      education from regional medical centres to community hospitals is an essential
      component of regionalization. The Perinatal Continuing Education Program (PCEP)
      has been successfully used for outreach education in more than 30 states since
      1979. This project tested the efficacy of implementing the PCEP strategy in
      Poland. PCEP was adapted to Polish conditions, translated, and implemented in
      four phases. The scheme allowed gradual transfer of ownership to Polish leaders
      and use of the existing regional structure to disseminate information from
      regional centres to community hospitals. Evaluation included measures of
      programme use (participation and completion rates) and acceptance (participant
      evaluation forms), cognitive knowledge (pre- vs. post-tests), and patient care
      (chart reviews). Of 2093 doctors, nurses and midwives who began, 1615 (77%)
      completed the programme, with higher completion by regional centre than community
      hospital staff. All participant groups responded favourably to the materials and
      expressed moderate confidence in their mastery of the information and skills.
      Test scores improved significantly for all phases and for all disciplines, with
      baseline and final scores consistent with degrees of previous professional
      education. Large baseline and inter-hospital variations in chart review data
      restricted analysis of care practices. A comprehensive perinatal education
      programme can be successfully transferred to a foreign health care system. We
      believe the following to be particularly important: multidisciplinary instructors
      and students; a self-instructional format; content aimed at practice rather than
      theory; and an organized implementation strategy co-ordinated by local personnel.

PMID- 9231142
TI  - Audit and summative assessment: system development and testing.
AB  - Registrars in general practice have to submit an audit project as one of four
      parts of summative assessment. A criterion-referenced marking schedule has been
      developed in the West of Scotland, consisting of five independent criteria all of
      which have to be judged above minimum competence to pass. A system was developed
      to test the instrument using a marking exercise which calculated the sensitivity
      and specificity of the assessment process, for different combinations of
      assessors. One hundred and two registrar audit projects were then assessed by
      three independent assessors. Ninety-two (90%) passed and 10 projects (10%) were
      referred back to the registrar as being below minimum competence. After
      resubmission six projects (6%) passed, two projects (2%) were still below minimum
      competence, and two (2%) were not resubmitted. A referral process for assessing
      the audit projects of general practice registrars has been developed to maximize
      the opportunity of finding a project below minimum competence.

PMID- 9231143
TI  - Computer awareness among medical students: a survey.
AB  - The objective of the study was to assess the attitude of Edinburgh University
      medical students towards computers and to evaluate the effects of changes in the
      curriculum and intercalated BSc towards computer knowledge. During March to
      November 1995 a questionnaire was distributed in lectures, seminars and tutorials
      to all Edinburgh University medical students. Overall, 65% of students returned
      the questionnaire, divided equally between both genders. Only 2% of students had
      not used a computer in the previous year. The most frequent application used was
      E-mail and the most frequent site, the Greenfield suite micro lab, within the
      medical school. The average score for self-perceived computer knowledge on a
      scale of 0-10 was 4.19. This score was significantly higher for the students who
      own a computer and who have an intercalated BSc honours degree as well as the pre
      clinical students compared to the clinical students. There is also a strong
      correlation between computer use and doing a second year special option module.
      With regards to attitude towards computers, 86% of students agreed that computer
      skills will be beneficial to them in their future career and 62% of all students
      wanted a structured course in computer use as part of the MB ChB course. There
      has been a general increase in computer literacy amongst the medical students in
      Edinburgh. This is specially so for the pre-clinical students who have had the
      brunt of the changes in the curriculum. The tendency for both the lower knowledge
      and use by the clinical students can, in part, be due to the accessibility of
      computers to these students.

PMID- 9231145
TI  - Reports on the excellence of the postgraduate training system in Portugal.

PMID- 9231144
TI  - Computer-assisted instruction in nutrition: a creative tool for medical
      education.

PMID- 9231146
TI  - Effects of auditory/visual and lexical/non-lexical comparisons on event-related
      potentials in a memory-scanning task.
AB  - A late parietal positivity (P3) and behavioural measures were studied during
      performance of a two-item memory-scanning task. Stimuli were digits presented as
      memorized items in one modality (auditory or visual) while the following probe,
      also a digit, was presented in the same or the other modality. In a separate set
      of experiments, P3 and behaviour were similarly studied using only visual stimuli
      that were either lexical (digits) or non-lexical (novel fonts with the same
      contours as the digits) to which subjects assigned numerical values. Reaction
      times (RTs) and P3 latencies were prolonged to non-lexical compared to lexical
      stimuli. Although RTs were longer to auditory than to visual stimuli, P3
      latencies to memorized items were prolonged in response to visually compared to
      auditorily presented memorized items, and were further prolonged when preceding
      visual probes. P3 amplitudes were smaller to auditory than to visual stimuli, and
      were smaller for the second memorized item when lexical/non-lexical comparisons
      were involved. The most striking finding was scalp distribution variations
      indicating changes in relative contributions of brain structures involved in
      processing memorized items, according to the probes that followed. These findings
      are compatible, in general, with a phonological memorization, but they suggest
      that the process is modified by memorizing the item in the same terms as the
      expected probe that follows.

PMID- 9231147
TI  - Prospective memory and divided attention.
AB  - In three experiments, we manipulated the processing demands of a concurrent task
      to test the hypothesis that an event-based prospective memory task satisfies a
      criterion of automaticity proposed by Hasher and Zacks (1979). As in the previous
      studies, a prospective memory task (pressing a key whenever a target word was
      presented) was embedded within a short-term memory task (remembering seven
      words). In addition, participants performed a concurrent memory task which varied
      in difficulty. Participants repeated either 0 to 6 randomly generated digits or a
      single word. In all three experiments, short-term memory performance was
      influenced by the concurrent memory load. Prospective performance, in contrast,
      was not affected by the memory load even though an attempt was made to increase
      the difficulty of the prospective task by manipulating the specificity of the
      target instructions (Experiment 2) and the number of target words (Experiments 2
      and 3). The results are discussed within the framework of automatic processing.

PMID- 9231148
TI  - Age-related differences in episodic odour recognition: the role of access to
      specific odour names.
AB  - This study addressed the relationship between semantic memory variables and
      episodic odour recognition across the adult lifespan. Young (19-34 years), young
      old (60-69 years), and old women (70-79 years) were tested in a number of
      measures of semantic memory: letter fluency, category fluency, vocabulary, odour
      familiarity, and odour naming. Odour recognition memory was assessed on two
      occasions: immediately after and 48 hours after inspection. Young women
      outperformed both groups of older women in odour recognition and odour naming,
      although the two older age groups did not differ. For all age groups, performance
      declined from immediate to delayed testing. Individual differences in fluency and
      vocabulary did not predict performance in odour recognition. Rather, odour
      recognition was related to the subjects' specific semantic knowledge of the
      odour, as indexed by familiarity and accuracy in odour naming. Hierarchical
      regression analyses indicated that age and odour naming were the most potent
      variables in predicting performance in both immediate and delayed odour
      recognition. Controlling for odour naming resulted in the effect of age
      disappearing, indicating the pivotal role of accessibility of odour names for
      successful episodic odour recognition, and for age-related differences in odour
      recognition.

PMID- 9231149
TI  - Differences in intentional retrieval during inclusion and exclusion tasks.
AB  - The process dissociation approach assumes that intentional retrieval processes
      operate in the same manner during inclusion and exclusion tasks. The present
      research shows that this assumption is not always tenable. After completing a
      word stem according to inclusion or exclusion instructions, subjects were asked
      whether they had recalled a word presented during study while completing the
      stem. Stem completion latencies were also recorded. When the exclusion task was
      described as a creativity test (Experiment 2), subjects recalled almost twice as
      many words during inclusion than during exclusion trials. Also, completion
      latencies were longer on inclusion trials, suggesting that on these trials
      subjects tried hard to remember old words. When instructions stressed that recall
      of old words was as important on exclusion as on inclusion trials (Experiment 1),
      recall rates did not differ significantly between both kinds of trials. However,
      completion latencies were significantly longer on inclusion trials, showing that,
      despite instructions, subjects still invested more effort in trying to remember
      old words during inclusion trials. The implications of these findings for future
      process dissociation research are discussed.

PMID- 9231150
TI  - Processing instructions and the generation effect: a test of the multifactor
      transfer-appropriate processing theory.
AB  - We report two experiments designed to test further the multifactor transfer
      appropriate processing explanation of generation effects (deWinstanley, Bjork, &
      Bjork, 1996). The present research focuses on the following assumptions: (a) that
      processing resources are limited and, thus, the processing of one type of
      information can be, and often is, incompatible with the processing of other types
      of information; and (b) that reading and generating differ in terms of the
      flexibility they permit for the distribution of the subject's processing
      resources across the available information in an experimental context. These
      assumptions were tested by examining the consequences of processing instructions
      on the occurrence of generation effects, and the lack thereof, in free recall and
      cued recall. Across both experiments, identical processing instructions had
      strikingly different consequences on the later free-recall and cued-recall
      performance of subjects who encoded targets by generating them versus reading
      them, a pattern consistent with the foregoing assumptions.

PMID- 9231151
TI  - Does articulatory suppression remove the irrelevant speech effect?
AB  - Salame and Baddeley (1982) reported that the effect of irrelevant speech on the
      serial recall of visually presented sequences was abolished when subjects
      performed articulatory suppression during presentation and recall of the target
      items. They argued that this is because suppression isolates visually presented
      material from the phonological store, which they consider to be the locus of the
      irrelevant speech effect. In the present experiment, an alternative
      interpretation of Salame and Baddeley's findings was investigated. Salame and
      Baddeley used nine-item sequences, and observed very low levels of recall when
      articulation was suppressed. It is therefore possible that Salame and Baddeley's
      failure to observe any additional effect of irrelevant speech reflects either a
      floor effect or else a strategic choice by subjects to abandon the use of a
      phonological memory code because of task difficulty. In the experiment reported
      here, this issue was investigated by using both six- and nine-item sequences.
      Results revealed no effect of irrelevant speech under articulatory suppression
      even at the shorter sequence length. The results therefore replicate and extend
      the findings of Salame and Baddeley (1982), and provide support for their view
      that visually presented material must be articulated before it becomes
      susceptible to interference from irrelevant speech.

PMID- 9231153
TI  - Pathogenic mechanisms of neuronal damage in the AIDS dementia complex.

PMID- 9231154
TI  - Routine diagnosis of large granular lymphocytic leukaemia by Southern blot and
      polymerase chain reaction analysis of clonal T cell receptor gene rearrangement.
AB  - AIMS: To compare the polymerase chain reaction (PCR) assay with standard Southern
      blot (SB) hybridisation for the detection of clonal T cell receptor (TCR) gene
      rearrangements in large granular lymphocyte (LGL) proliferations; to evaluate the
      reliability and practicality of the methods for routine diagnostic use; and to
      determine the sensitivity of the PCR method. METHODS: Blood lymphocytes were
      isolated from 12 patients with persistent CD3+CD8+ lymphocytosis with LGL
      morphology. Clonal rearrangements of the TCR gene were demonstrated by SB
      hybridisation with a TCR beta constant probe, and by PCR amplification of
      portions of the TCR beta and TCR gamma genes. RESULTS: Monoclonal TCR beta gene
      rearrangements were detected in eight patients (67%) by PCR analysis and five
      patients (42%) by SB hybridisation. PCR analysis also showed that seven patients
      (58%) had monoclonal TCR gamma gene rearrangements. All cases which had TCR beta
      clonal rearrangements shown by SB hybridisation were similarly identified by PCR.
      Sensitivity tests suggested that the TCR beta PCR technique was capable of
      detecting clonality in as little as 50 pg of DNA. The TCR beta primers could
      detect one clonal cell in approximately 200 or more normal cells (< 0.5%), a
      sensitivity level that at least doubles that of the SB hybridisation technique.
      CONCLUSIONS: The use of PCR technology proved to be superior to SB hybridisation
      for the routine investigation of suspected cases of LGL leukaemia. Nine patients
      (75%) in this study were found to have TCR beta and/or TCR gamma monoclonal gene
      rearrangements. This approach is ideal for distinguishing between reactive and
      clonal LGL proliferation in a routine diagnostic laboratory.

PMID- 9231152
TI  - CD44 and the adhesion of neoplastic cells.
AB  - CD44 is a family of transmembrane glycoproteins that act mainly as a receptor for
      hyaluronan. It can also bind some other extracellular matrix ligands (chondroitin
      sulphate, heparan sulphate, fibronectin, serglycin, osteopontin) with lower
      affinity. CD44 is encoded by a single gene containing 20 exons, 10 of which (v1
      v10) are variant exons inserted by alternative splicing. The standard,
      ubiquitously expressed isoform of CD44, does not contain sequences encoded by
      these variant exons. Numerous variant isoforms of CD44 containing different
      combinations of exons v1-v10 inserted into the extracellular domain can be
      expressed in proliferating epithelial cells and activated lymphocytes. CD44 plays
      a significant role in lymphocyte homing. Both alternative splicing and
      glycosylation influence receptor function of the molecule, usually reducing its
      affinity to hyaluronan. The cytoplasmic domain of CD44 communicates with the
      cytoskeleton via ankyrin and proteins belonging to the ezrin-moesin-radixin
      family. Relatively little is known about the intracellular events following
      interactions of CD44 with its ligands. Some variant isoforms, especially those
      containing sequences encoded by v6-v10, are overexpressed in both human and
      animal neoplasms. In a rat pancreatic adenocarcinoma model one of the variant
      CD44 isoforms was proved to be determinant in the metastatic process. For some
      human neoplasms (carcinomas of the digestive tract, non-Hodgkin's lymphomas,
      thyroid carcinomas, and others) correlations have been made between the
      particular pattern of CD44 variants produced by neoplastic cells and
      clinicopathological parameters of tumours, such as grade, stage, presence of
      metastases, and survival. In vitro studies indicate that modifications of CD44
      expression result in different ligand recognition and influence cell motility,
      invasive properties, and metastatic potential of experimental tumours.
      Investigation of CD44 neoexpression can be useful both in early cancer diagnosis
      and in predicting tumour behaviour. It can also contribute to better
      understanding of molecular mechanisms leading to neoplastic transformation.

PMID- 9231155
TI  - Expression of a novel mRNA in human head and neck squamous cell carcinoma cells.
AB  - AIMS: The differential display reverse transcription polymerase chain reaction
      (DDRT-PCR) technique was used to search for differences between the mRNA
      expression profiles of squamous cell carcinoma (SCC) cell lines established from
      head and neck tumours and normal keratinocytes from the mucosa of the upper
      aerodigestive tract. METHODS: Total RNA prepared from both cell types was reverse
      transcribed into cDNA then amplified in a PCR mixture. To compare the
      electrophoretic patterns, mRNAs were amplified by nested PCR using specific
      oligonucleotides. Additionally, using labelled cDNA probes, northern
      hybridisation was carried out on three cancer cell lines of different origin, a
      biopsy from a parotid gland pleomorphic adenoma, healthy mucosa, and
      keratinocytes. RESULTS: Comparison of the separated bands revealed a fragment
      with a differential expression pattern in the SCC cells. This cloned sequence of
      a 336 base pair mRNA fragment exhibited no significant homology with known
      transcripts. Additionally, after amplification and sequencing of the 3' end of
      the fragment no homology with a known human gene sequence was found. However, low
      homology with a genomic sequence of a nematode was found. Northern hybridisation
      confirmed the selective expression of this fragment in SCC cells versus the
      cancer cell lines of different origin, the biopsy of the pleomorphic adenoma,
      keratinocytes, and healthy mucosa. CONCLUSIONS: This is the first differentially
      expressed human genome transcript of squamous cell carcinoma of the head and neck
      identified by DDRT-PCR. It may prove useful, in the future, to characterise this
      tumour type.

PMID- 9231156
TI  - Fas ligand is not only expressed in immune privileged human organs but is also
      coexpressed with Fas in various epithelial tissues.
AB  - AIMS: To confirm the recent data obtained in mice, showing that the Fas ligand
      (FasL) is involved in the phenomenon of "immune privilege" (the apparent defect
      of the immune system in specific anatomical sites) and to extend this finding to
      humans. METHODS: The expression of FasL was analysed in a panel of histologically
      normal human tissues by reverse transcriptase polymerase chain reaction and
      Western blotting. The tissues sampled were brain, breast, bone marrow,
      oesophagus, kidney, liver, lung, lymph node, ovary, pancreas, pituitary gland,
      prostate, spleen, stomach (antrum and fundus), striated muscle, testis, thyroid,
      and uterus. These were obtained from patients with various neoplastic and non
      neoplastic disorders; placental tissue was obtained after normal obstetric
      delivery, and spontaneous or voluntary abortion. RESULTS: Strong FasL expression
      was detected in testis and placenta. FasL expression was also detectable,
      although it was seen to a lesser extent, in oesophagus, prostate, lung, and
      uterus, which also coexpressed variable amounts of Fas mRNA or protein or both.
      The other organs tested for FasL expression were all negative. CONCLUSIONS: FasL
      in humans is expressed predominantly in immune "sanctuaries" such as testis and
      placenta, suggesting that, similar to mice, this expression may contribute to the
      immune privileged status of these organs, by preventing dangerous inflammatory
      responses. The coexpression of FasL and Fas in particular epithelia suggests that
      the physiological cell turnover of some tissues may be regulated by the Fas-FasL
      apoptotic pathway.

PMID- 9231157
TI  - Interphase ribosomal RNA cistron silver staining in refractory anaemias with and
      without excess blasts.
AB  - AIM: To evaluate the haemopoietic function of bone marrow blood forming cells in
      human myelodysplastic syndromes (MDS) by silver staining of nucleolar organiser
      regions (AgNORs). METHODS: Nucleoli were investigated in bone marrow blast cells
      and in erythroid, granulocytic, and megakaryocytic cells from 12 haematologically
      healthy subjects, and from 26 patients with MDS, including 14 with refractory
      anaemia (RA), nine with RA with excess blasts (RAEB), and three with RAEB in
      transformation (RAEB-t). The investigation was performed before treatment using a
      one step silver staining method. In each case 50 to 100 blasts, promyelocytes,
      myelocytes, immature (pronormoblastic and basophilic normoblastic) and mature
      (polychromatic normoblastic) erythroid elements, and megakaryocytes were
      evaluated for the mean numbers of nucleoli and AgNORs per nucleus. Student's t
      test was used to compare the patient and control groups. Other statistical
      analyses were carried out by the computer assisted "HEMA" system. RESULTS:
      Compared with controls, the number of AgNORs in blasts, promyelocytes, immature
      erythroid elements, and megakaryocytes was decreased, whereas in myelocytes and
      polychromatic normoblasts it was similar. There was also a difference in the
      AgNOR scores in blood forming cells from patients with RAEB/ RAEB-t v RA.
      CONCLUSIONS: The loss of AgNOR sites in cellular series in MDS may result from
      the decrease of their proliferative potential with disease progression, intrinsic
      defects in maturation, and extensive apoptosis.

PMID- 9231159
TI  - Absence of human papillomavirus genomic sequences detected by the polymerase
      chain reaction in oesophageal and gastric carcinomas in Japan.
AB  - AIMS: To estimate the occurrence of human papillomavirus (HPV) infection in
      oesophageal or gastric carcinomas in patients in Japan. METHODS: 103 oesophageal
      and 99 gastric carcinomas were investigated by polymerase chain reaction (PCR)
      assays using two consensus (targeting either the L1 or the E6-E7 regions) and two
      type specific (type 16 and 18) primer sets. A beta globin gene specific primer
      set was also applied to examine the quality of the extracted DNA. RESULTS:
      Amplification of beta globin gene was clearly visible in 92 (89.3%) of the 103
      oesophageal, and 89 (89.8%) of the 99 gastric carcinoma specimens. However, the
      entire series of tumour DNA was negative for HPV sequences by PCR assay using all
      four primer sets. CONCLUSION: HPV is not likely to be involved in oesophageal or
      gastric tumorigenesis in Japanese patients.

PMID- 9231158
TI  - HHV8 and Kaposi's sarcoma: a time cohort study.
AB  - AIMS: The recent finding that human herpes virus 8 (HHV8) is found in the
      majority of Kaposi's sarcoma (KS) cases supports the epidemiological observation
      that the tumour may be caused by an infectious agent. This study aimed to address
      when and how HHV8 evolved. METHODS: A cohort of African endemic KS (49 samples
      from 45 patients) and European KS (18 samples from 13 patients), spanning 27
      years, was assessed for the presence of HHV8 by both standard solution phase
      polymerase chain reaction (PCR) and the newly described technique of TaqMan PCR.
      RESULTS: HHV8 was present in approximately 49% (24 of 49 tissue samples) of the
      African cases and in more than 90% (16 of 18 tissue samples) of the European
      cohort, in keeping with recent seroepidemiological data. CONCLUSIONS: HHV8 is
      strongly linked to the development of KS; however, in some patients, other
      factors may operate. The utility and flexibility of TaqMan PCR in detecting low
      copy viral target in human tissues was demonstrated.

PMID- 9231160
TI  - Novel method for detection of small amounts of RNA based on the semi-nested
      polymerase chain reaction.
AB  - A technique for the amplification of very small quantities of cDNA based on a
      semi-nested polymerase chain reaction system has been developed. The technique
      uses an additional blocking oligonucleotide "primer" in the second round nest
      which is complementary to one of the first round primers. This prevents
      amplification of first round product or of any other unwanted products dependent
      on that primer, but allows amplification of second round product, using first
      round product as the template. The second round primers are added through the oil
      layer, eliminating the possibility of introducing first round product aerosol
      into the atmosphere, as would be the case in a fully nested system. Contamination
      is therefore minimised, while amplification of the desired product is maximised.

PMID- 9231161
TI  - p53 gene mutations, and CYP1A1 and GSTM1 genotypes in pulmonary squamous cell
      carcinomas.
AB  - To investigate mechanisms causing p53 mutations in lung cancer cases, relations
      between p53 gene mutations and aetiological factors such as smoking history or
      family history of cancers cases. The contribution of genotypes related to
      carcinogen metabolism (CYP1A1 and GSTM1) was also analysed. p53 mutations were
      observed in 13 cases (37.5%). Seven (53.8%) of the 13 patients with p53 mutation
      compared with five (22.7%) of 22 patients without had a family history of cancer.
      However, there was no significant relation between p53 mutation or family history
      of cancer and CYP1A1 or GSTM1 genotypes. In conclusion, p53 mutation might be
      associated with the inherited characteristics that result in familial aggregation
      of lung cancer; however, this association was not explained by genotypes of
      enzymes related to carcinogen metabolisms.

PMID- 9231162
TI  - Cell cycle regulatory proteins--an overview with relevance to oral cancer.
AB  - The cell cycle is controlled by a number of highly conserved proteins, found in
      species as diverse as yeast and mammals. The study of these proteins is a rapidly
      advancing field that is increasing our understanding of normal and abnormal cell
      division. Disruption of the cell cycle has been demonstrated in several different
      types of neoplasm, and there is increasing evidence that, in head and neck
      tumours, there is aberrant control of cyclins, cell cycle protein kinases and
      their inhibitors. Because of the phase specificity of some of the control
      proteins, antibodies to them are proving to be of value in studying cell kinetics
      of both normal tissues and malignant tumours.

PMID- 9231163
TI  - Glutathione S-transferase pi expression in matched human normal and malignant
      oral mucosa.
AB  - Over-expression of glutathione S-transferase pi (GST-pi) class isozyme is often
      associated with malignant transformation and/or drug resistance. To determine
      whether GST-pi is implicated in betel and tobacco related oral carcinogenesis
      and/or drug resistance, its expression was studied in oral untreated primary
      squamous cell carcinomas (SCCs), recurrent tumours and matched normal oral
      tissues by immunohistochemical and immunoblotting techniques. The GST-pi
      expression in primary tumours predominantly varied from mild to moderate levels
      and no significant difference in its expression was observed in the matched
      normal tissue surrounding these lesions. Mild to moderate levels of GST-pi
      expression in the oral mucosa of consumers of betel and tobacco observed in the
      matched normal tissues may support the physiological role of this detoxification
      enzyme in the metabolism of xenobiotics and elimination of toxic constituents of
      tobacco. The hallmark of the study is the significant increase in GST-pi
      expression in recurrent oral SCCs, compared to the matched normal tissues, as
      well as primary oral tumours, suggesting its potential role as an indicator of
      prolonged exposure to carcinogens, or prognosis of the disease.

PMID- 9231164
TI  - Risk of tongue cancer associated with tobacco smoking and alcohol consumption: a
      case-control study.
AB  - Recent studies indicate that cancer of the tongue is increasing rapidly among the
      younger population in many parts of the world. Few studies, however, have
      directly examined the risk factors for the disease. A case-control study was
      conducted in Beijing, China to investigate risk factors for tongue cancer. A
      total of 111 cases and 111 controls aged 20-80 years were included in this study.
      The results show that risk of tongue cancer is significantly elevated among ex
      smokers (OR = 2.24, 95% CI = 1.09-4.62) and among current smokers (OR = 2.73, 95%
      CI = 1.26-5.91). The risk increases with increasing tobacco consumption, as
      reflected by both cigarette equivalents smoked per day and lifetime pack-years of
      tobacco smoking. Quitting smoking was associated with a reduction of the risk of
      tongue cancer. The numbers of cases in the study, however, is small, preventing
      further analyses during the years after quitting smoking. Overall, alcohol
      drinking was not found to be significantly associated with the risk of tongue
      cancer in this study (OR = 1.20, 95% CI = 0.58-2.50 for current drinkers).
      However, a marginally significant association was found for those who drank
      spirits at least 5 days a week (OR = 2.34, 95% CI = 0.90-6.06). A suggestion of
      effect modification for smoking and alcohol drinking was observed in this study.

PMID- 9231165
TI  - Mixed odontogenic tumours and odontomas. Considerations on interrelationship.
      Review of the literature and presentation of 134 new cases of odontomas.
AB  - Based on a world-wide literature survey of published cases of "mixed odontogenic
      tumours" (ameloblastic fibroma, fibrodentinoma and fibro-odontoma) and
      complex/compound odontomas (including 134 own cases of odontomas) the authors
      present data showing the complex nature of these lesions. The authors suggest the
      following work hypothesis regarding the pathogenesis and relationship between the
      "mixed odontogenic tumours" and the odontomas. The tumours develop along two
      separate lines: (I) the neoplastic line comprising only one tumour, the
      ameloblastic fibroma (AF) and the closely related ameloblastic fibrodentinoma
      (AFD). (II) The hamartomatous (or the developing complex odontoma (DCO) line
      comprising: (1) The AF (and AFD). Differences in age and biological behaviour
      indicate that some AF are true benign neoplasms, whereas others are hamartomas
      presenting the first stage in the DCO-line. (2) The AF-O represents the second
      stage of the DCO-line developing into (3) the fully mineralized complex odontoma.
      Lastly, the authors suggest that the compound odontoma should be considered not
      as an alternative final stage to the complex odontoma but rather as a
      malformation (with a high degree of histomorphological differentiation)
      pathogenetically closely related to the process producing hyperodontia, "multiple
      schizodontia" or locally conditioned hyperactivity of the dental lamina.

PMID- 9231166
TI  - Attitude towards smoking and oral cancer prevention among northern Italian
      dentists.
AB  - The aim of the study was to evaluate the smoking habits of Northern Italian
      dental practitioners and their basic skills in the prevention of oral cancer. 217
      of the 250 dental practitioners (86.8%) contacted by telephone from September to
      December 1994, answered a simple questionnaire. One third of the sample
      interviewed was formed by current smokers; nevertheless 60.8% of them always
      advise their patients to give up smoking. Only a relatively small percentage of
      the questioned dental practitioners (10.6%) do not examine the oral mucosa of the
      patients on a regular basis and 40% of responders had made a clinical diagnosis
      of oral cancer in the past. The lack of a specific dental education was
      associated with less scrupulous examination of the oral soft tissues and minor
      experience of cancer diagnosis. Despite their smoking habit, Northern Italian
      dental practitioners self-reported encouraging behaviour towards primary and
      secondary oral cancer prevention.

PMID- 9231167
TI  - Experimental tongue cancer in desalivated rats.
AB  - A group of 39 rats underwent excision of the submandibular and sublingual glands
      and ligation of the parotid ducts through the midventral incision of the neck,
      while the control group (41 rats) underwent a sham operation. All rats were
      administered 4NQO in a final concentration of 0.001% in drinking water. At 7, 14,
      22 and 28 weeks after administering 4NQO, both groups of rats were killed and
      their tongues dissected, inspected and then fixed in 10% buffered formalin for
      histopathological examination. Clinical examination during the first 14 weeks
      revealed that rats in both groups looked healthy and no differences in body
      weight were noticed. Afterwards, the average weight gain of the desalivated rats
      was lower than in the control group (P < 0.01). The number of macroscopic oral
      lesions increased with time in both groups. However, in the desalivated rats, the
      first identifiable lesions were seen as early as week 7, whereas in the control
      group macroscopic lesions were seen only after 22 weeks. Histological examination
      revealed more affected rats in the desalivated group in the first 14 weeks after
      administering the carcinogen; lesions showed more severe pathological changes
      including two cases with evidence of squamous cell carcinoma. The differences
      between the desalivated groups and control decreased after 22 weeks with almost
      no differences at the end of the experiment.

PMID- 9231169
TI  - Adenolymphoma and non-Hodgkin's lymphoma of the salivary glands and oral cavity
      in immunocompetent patients are not associated with latent Epstein-Barr virus.
AB  - The presence of Epstein-Barr virus (EBV) was studied in specimens of 50 primary
      non-Hodgkin's lymphomas (NHL) of the salivary gland and the oral cavity and 11
      solitary adenolymphomas of the parotid gland, using EBER-1/2 in situ
      hybridisation and by immunohistochemistry for the detection of latent membrane
      protein-1 (LMP-1). None of the patients were tested for HIV-infection, nor were
      there any clinical signs to suspect HIV-infection. In one adenolymphoma, few
      reactive EBER-1/2 positive cells were detected. In this case staining for LMP-1
      was negative. In one oral B-cell NHL, EBER-1/2 positive lymphoma cells were
      identified; these cells also expressed LMP-1. None of the 31 oral (30 B-cell and
      one T-cell) and 18 salivary gland (all B-cell) NHLs and none of the 10
      adenolymphomas were EBER-1/2 positive or expressed LMP-1. These results indicate
      that EBV is not involved in the pathogenesis of oral and salivary gland primary
      NHL and adenolymphoma in immunocompetent patients.

PMID- 9231168
TI  - Atypical mitoses in lesions of the oral mucosa: a new interpretation of their
      impact upon tumorigenesis.
AB  - With regard to the classification of precancerous lesions, this is the first
      approach to compare modes of the cell cycle in benign lesions and neoplasia in
      oral mucosa. The main objective of this study was to find parameters that
      indicate possible progress in tumorigenesis. In this respect, histomorphological
      changes were compared with the DNA content of individually identified nuclei in
      interphase and division. Thus, hyperplastic tissue was discriminated from
      neoplastic tissue by investigating pyogenic granulomas (27 cases), epulides (17),
      simple forms of ulcers (12), low-grade dysplasias (14), high-grade dysplasias
      (15) and carcinomas (41). After diagnosis, Feulgen DNA was quantified from
      interphase nuclei and chromosome division figures (CDFs) in 8- and 15-micron
      sections. Interphase nuclei from cases of hyperplasia were constantly found in
      the range of mitotic amounts, i.e. 2 c-4 c DNA. A 4 c value was therefore
      recorded for mitotic figures. Measurements in this type of lesion were carried
      out with a high degree of accuracy (CV at 0.05). However, cases of neoplasia
      showed CDFs that were frequently beyond the mitotic range (> 4.8 c) in
      morphologically identified prophases, metaphases and both hemispheres of
      telophases. The distribution profile of interphase nuclei was characterised by
      DNA aneuploidy, with a 5 c exceeding rate (ER) > 5%. This biological variability
      in the amount of nuclear DNA was reflected by CV > 0.20. The quantitative results
      corroborated the morphological two-level classification of premalignant lesions
      caused by endoreplication associated with neoplasia. Thus, regular mitotic
      replication appeared to be progressively substituted by genome multiplication.

PMID- 9231170
TI  - Radiotherapy in the treatment of verrucous carcinoma of the oral cavity.
AB  - Verrucous carcinomas are considered to have poor radioresponsiveness and
      radiotherapy has been reported to induce anaplastic transformation. Surgery has
      been considered to be the primary mode of treatment for these tumours. The
      clinical features, response to radiotherapy, survival and prognostic factors of a
      group of 53 patients with oral verrucous cancers, were studied and compared to
      patients with oral well-differentiated, squamous cancers, treated during the same
      time period. The buccal mucosa was the commonest primary site in both groups. 42
      patients with verrucous cancer underwent primary radiotherapy and 11 underwent
      primary surgery. Complete response to radiotherapy was achieved in 76% of
      patients with verrucous cancer and partial response in 24%. Patients with
      verrucous cancer had a five year actuarial disease-free survival of 66% and
      overall survival of 86%. The corresponding survival figures were 43% and 56% in
      well-differentiated squamous cancers (P = 0.004). Composite stage of disease was
      a significant predictor of disease-free survival in both groups. None of the 16
      patients with verrucous cancers that recurred after radiotherapy, had features of
      anaplastic transformation. Oral verrucous carcinoma appears to have similar
      radioresponsiveness and improved disease-free survival, compared to well
      differentiated squamous cancers. The treatment policies for other oral squamous
      cancers are applicable to these tumours.

PMID- 9231171
TI  - Intensive chemotherapy using cisplatin and fluorouracil followed by radiotherapy
      in advanced head and neck cancer.
AB  - This protocol was designed to achieve an improvement in the overall and disease
      free survival in locally advanced, previously untreated carcinoma of the head and
      neck. 53 patients (pts) with locally advanced Stages III and IV, MO squamous cell
      carcinoma of the nasopharynx, larynx, paranasal sinuses, oral cavity, oropharynx,
      hypopharynx and one of unknown origin were treated with intensive chemotherapy
      followed shortly thereafter by radiotherapy. Induction chemotherapy consisted of
      two cycles of cisplatin 100 mg/m2 over 60 min on day 1, plus 5FU 1000 mg/m2
      continuous infusion over 24 h on days 2-5, with a 10-day interval between the two
      cycles, followed by definitive radiotherapy after 10 days. The overall response
      rate to chemotherapy was 79%, with a 28% complete response (CR) rate and a 51%
      partial response (PR) rate. The overall CR rate after radiotherapy was 70%. With
      a median follow-up period of 48 months, the 5-year actuarial survival and disease
      free survival rates were 67% and 45%, respectively. No difference was found in
      the survival probability of pts with carcinoma of the nasopharynx, larynx or
      other primary sites. The survival of pts with a performance status (PS) < or = 1
      was better than pts with PS > 1, 72% versus 51% (not significant). The survival
      probability of complete responders to chemotherapy was superior than the survival
      of non-complete responders to chemotherapy, 100% versus 54% [P = 0.001]. The main
      toxicity was mucositis during radiotherapy. In conclusion, this treatment regimen
      demonstrated a high CR rate and survival probability in pts with locally advanced
      and mostly inoperable head and neck cancer.

PMID- 9231172
TI  - Non secretory multiple myeloma involving the maxilla: report of a case with
      update of biology and new approaches to management.
AB  - Non-secretory myeloma of the maxilla is a rare occurrence. A case involving the
      maxillary tuberosity is presented along with an update on current understanding
      of myeloma biology, recent insights which provide, for the first time, hope of
      significant longer term survival. New therapies and diagnostic methods, as well
      as the importance of involvement of the special care dentist, in management of
      the impacting effects of both disease and treatments are discussed.

PMID- 9231174
TI  - Granular cell ameloblastoma versus central odontogenic granular cell tumor.

PMID- 9231173
TI  - Basaloid squamous cell carcinoma of the maxilla.
AB  - The study reports the first case of basaloid squamous cell carcinoma (BSCC)
      involving both the oral mucosa and the tuberosity area of the maxilla. The tumour
      showed many histological similarities to cases previously reported, though
      mitoses were not frequent. The immunoreactivity for cytokeratin, S-100, vimentin,
      Ki-67, p53, c-erbB-2 and bcl-2 was also investigated. Immunostaining for the bcl
      2 protein showed a high extent of positive cells, although only a moderate
      staining intensity. Staining for c-erbB-2 was negative. The pathological findings
      and the immunoreactivity may indicate that BSCC is not as high a grade carcinoma
      as previously suggested. Additional studies are thus clearly needed to confirm or
      reject this impression.

PMID- 9231175
TI  - Acupuncture treatment of patients with radiation-induced xerostomia.

PMID- 9231176
TI  - [Psychosomatics in orthopedics].
AB  - Psychosomatics applies to orthopaedic surgery in several ways. Illness, accident,
      pain, physical handicap present an individual and subjective meaning in each
      patient story. Every one can date his first symptom back to an important
      emotional event. The way the illness and its symptoms break out, reveals patient
      personality. Illness, accident, and their surgical treatment may be felt as a
      psychic traumatism which troubles mental stability. Discussion with a
      psychologist enables to reveal the meaning which everyone gives to his symptoms,
      and to understand why it is sometimes difficult for the patient to give them up.
      Finally, psychosomatics shows that the healing function of orthopaedic surgery
      can sometimes concern negotiation of a compromise between acceptable physical
      pain and bearable physical pain, more than the desire to totally suppress painful
      or functional complaint.

PMID- 9231177
TI  - [A morphometric study of the femoro-patellar joint from lateral x-ray view].
AB  - PURPOSE OF THE STUDY: The goal of this study was to specify criteria of femoro
      patellar joint normality on lateral view. MATERIAL: This study was based on
      radiological examination of 102 knees in 51 adults (average age 26.1 years). It
      concerned 29 women and 22 men that had never suffered from their knee and were
      supposed healthy. METHODS: The radiological protocol was the following: a lateral
      view at 45 degrees of flexion, two lateral views in extension, with and without
      quadriceps contraction. The analysis was focused on patellar surface aspect, its
      height, its depth and covering measurement. RESULTS: We found 83.7 per cent of so
      called "normal" patellar surface, and 12.7 per cent of "abnormal" patellar
      surface (dysplasia) in the absence of pain. DISCUSSION: We have confirmed figures
      advanced in others series of the literature concerning patellar height and
      patellar surface, as well as patellar surface depth and covering. We have
      underlined the interest of lateral views; in extension with quadriceps contracted
      and relaxed. Finally, we have defined a trochleo-patellar sign that allows to
      correlate patellar height to patellar surface height (ITP = 0.35 to 0.84).
      CONCLUSION: This study insists on the interest of radiological lateral views of
      the knee and determine criteria for normalities.

PMID- 9231179
TI  - [Treatment of metaphyseal fractures of the tibia by the Ilizarov external
      fixator].
AB  - PURPOSE: This external fixation was used for 46 of 60 cases of proximal tibial
      metaphyseal fractures, over a 10 years period. The choice of an external fixation
      was determined by the poor reputation of internal fixation for even complex
      closed fractures. The reasons for the choice of the Ilizarov device were: the
      possibility of fitting the fixation pins close to the knee joint if necessary,
      the circular nature of the system, and finally the possibility of adding an
      intrafocal mounting (I.F.M.) which can bring the displaced bone fragments
      together using shaped blockstops pins. The program theoretically foresaw an
      initial sequence using external fixation until bone continuity was achieved,
      followed by a complementary plaster for one or two months. MATERIALS: 7 of the 46
      fractures were lost for follow-up. Of the remaining 39 cases, there were 5 early
      complications: one knee septic arthritis which led to stop the method before the
      second month. Each of these 5 failures were due to improper use of the method. 34
      cases have been followed for more than two years. RESULTS: 29 cases of
      consolidation of which 3 initial displacements were wrongly considered as
      acceptable. There was no case of displacement while the fixation was in place.
      There were 5 nonunions: 2 at the diaphyseal level in long metaphyso-diaphyseal
      fractures, 2 were comminutive metaphyseal fractures in which the fixation had
      been removed by error before the third month. With this fixation, neither the
      traumatic opening, nor the presence of a fibular fracture significantly affected
      consolidation. The healing period was however longer when the fracture was more
      extensive and comminutive. The bone gaps were treated by interfocal mounting
      (I.F.M.) but loss of bone stock persisted; they affected the occurrence of
      nonunion. CONCLUSION: Each failure of the method is explained by its improper
      use. The Ilizarov fixation is an excellent mechanical response to these
      fractures: on condition that the technical rules are respected, that an
      intrafocal mounting is used to remove interfragmentary gaps, and that the fixator
      is kept in place long enough, according to the size and comminutive nature of the
      fracture. This fixation is reliable in these conditions but does not compensate
      intrafocal bone loss exceeding 40 per cent of the metaphyseal bone mass.

PMID- 9231178
TI  - [Post-traumatic epiphysiodesis of the distal end of the tibia in children].
AB  - PURPOSE OF THE STUDY: Thirteen distal traumatic epiphyseal closures of the lower
      end of the tibia are studied. A bony bridge resection was performed in nine
      cases. The aim of this study was to define the kind of injury that drives to
      epiphysiodesis in this localisation, and secondly to define the factors that may
      influence the results of de-epiphysiodesis. MATERIALS AND METHODS: One hundred
      and eighty-eight children were hospitalized between 1981 and 1995 for the
      treatment of a fracture of the lower end of the tibia. Six epiphysiodesis
      followed a Mac Farland lesion. Six epiphysiodesis followed a Salter and Harris
      Type-II injury. One epiphysiodesis followed a triplane fracture. The diagnostic
      of epiphysiodesis was performed at an average of 12 months after injury. The bony
      bridge interested less than 50 per cent of the growth plate in all cases. There
      was a varus deformation between 7 degrees and 20 degrees in six cases (average
      13.8 per cent). Ten surgical procedures were performed: one fibular bi-focal
      epiphysiodesis and nine tibial de-epiphysiodesis including a resection of the
      bony bridge filled with acrylic cement. Two children were not operated because
      they were close to the end of growth and there was no varus deformation. One
      child was not reviewed. RESULTS: There was a significant correlation between the
      children age and the importance of the ankle varus deformation. The younger the
      children were and the more important the varus deformation was. Only three de
      epiphysiodesis had a good clinical and radiological result. In five cases, a
      second surgical procedure was necessary. Fibular bi-focal epiphysiodesis gave a
      good clinical result. DISCUSSION: In this location, Harris and Salter type II
      fractures may have a poor prognosis for growth if the injury occurred with high
      energy. Varus deformation is a common way to discover epiphysiodesis in this
      location. There was no correlation between the children age and the result of the
      de-epiphysiodesis, and between the delay since injury and the de-epiphysiodesis
      result. There was a correlation between the result and the presence of a varus
      dexasation in the ankle. The more important the varus was and the poorer the
      result was. CONCLUSION: Mac Farland lesion and Salter and Harris type II lesion
      drive to epiphysiodesis more often than any other distal tibial fracture. Varus
      desaxation is more important in younger children and seems to determine de
      epiphysiodesis results. But over all, de-epiphysiodesis has a poor prognosis in
      more than 60 per cent of cases.

PMID- 9231180
TI  - [Conservative treatment of stress fractures of the tarsal navicular in athletes].
AB  - PURPOSE OF THE STUDY: The purpose of the study was to propose an algorhythm for
      nonoperative treatment of partial tarsal navicular stress fractures in athletes,
      based on the results of the authors prospective research, conducted in 17
      athletes. MATERIALS AND METHODS: The series included 17 patients with 18 partial
      tarsal navicular stress fractures (9 women and 8 men), average age 20.1 years.
      Patients were 10 track and field athletes mainly sprinters, 3 basketball players,
      two handball players, one soccer player and one volleyball player. After
      undergoing detailed physical examination which included x-ray examination, all
      patients also underwent bone scanning, and some kind of tomographic imaging (CT,
      MR) was done in all patients. Since all patients suffered from partial tarsal
      navicular stress fracture (fracture spreaded saggitally to maximal dorsal half of
      the bone) nonoperative treatment was conducted. Immobilization in a non weight
      bearing short-leg cast for a period of 6-8 weeks was followed by rehabilitation
      treatment consisting of 4 consecutive stages, each lasting 2 weeks. Control
      examination after each stage determined if patients could proceed to the
      following stage or if they should remain in the same stage for another two weeks.
      RESULTS: Patients were followed up from one to five years (average 33.9 months)
      and proposed algorhythm of nonoperative treatment resulted in all, except two
      athletes, returning to their previous level of competition activity. The average
      time period between initiation of treatment and resumption of full sports
      activity was 24 weeks (range 17 to 32 weeks). One stress fracture recurrence was
      encountered although all patients returned to sports activities and are
      constantly being monitored. DISCUSSION: No complex tarsal navicular stress
      fractures was found in our series. In our opinion the diminishing number of
      complete fractures is a consequence if quicker and more precise diagnosis. The
      period between the onset of symptoms and the time of correct diagnosis is
      becoming shorter. In our patients, this period was 3.3 months. The nonoperative
      treatment for tarsal navicular stress fractures was suggested with a wide variety
      of procedures. Based on the results if their prospective study the authors
      propose an algorhythm of conservative procedures in the treatment of partial
      tarsal navicular stress fracture. CONCLUSION: If clinical indication of tarsal
      navicular stress fracture is confirmed by a positive bone-scan, a CT or MRI
      exploration is required to distinguish stress reaction from stress fracture. In
      partial tarsal navicular stress fractures, immobilisation in a short-leg cast
      with nonweightbearing for 6 to 8 weeks depending of the magnitude of the fracture
      is required. This is followed by a treatment consisting of 4 two-weeks stages
      which clinically monitored. The previous phase can be repeated for another two
      weeks, depending of clinical findings. This algorhythm of nonoperative treatment
      of partial tarsal navicular stress fractures allowed in all athletes a return to
      competitive activity.

PMID- 9231181
TI  - [Pyogenic sacroiliitis in children. Apropos of 11 cases].
AB  - PURPOSE OF THE STUDY: Sacroiliitis in children is a rare disease. Since 1878,
      only 100 cases have been reported in the international literature. MATERIALS AND
      METHODS: We reviewed a series of 11 cases (mean age of 7.75 years) with a delay
      of 45 months. All the patients had limp, and hip pain. RESULTS: The clinical
      examination found each time F.A.B.E.R.E. and Glaensen signs. The hip mobility was
      limited most of time. There was a non specific inflammatory syndrome.
      Roentgenogram signs were delayed, and associated widening of the joint, geodes,
      condensation, and at an ultimate stage, fusion of the joint. Tc 99m scintigraphy
      always showed the localisation. DISCUSSION: This examination shortened the
      diagnosis delay, C-T scan was performed twice. It allowed visualize the local
      extension and complication such as abscess. It facilitated the indication of the
      surgical approach, and results can be appreciated through follow up CT scan
      studies. The germ was rarely determined as it has been reported in the
      literature. Therefore an articular ponction must be performed each time a
      sacroiliitis is suspected, under general anesthesia and associated to an
      arthrography or under CT scan control. Surgical drains were placed five times
      only. The authors limited their indication to an important collection, an
      abscess, or an intra-articular sequestra. CONCLUSION: At the maximum follow up
      (mean 45 months) all patients had a normal clinical exam. Each time there were
      joint modification on the roentgenogramm but without any functional correlation.

PMID- 9231182
TI  - [Ultrasonography in the diagnostic approach of septic arthritis].
AB  - PURPOSE OF THE STUDY: Septic arthritis is frequent in Tunisia and is responsible
      for orthopedic sequela. The purpose of this study was to establish the indication
      and the viability of ultrasound scanning in the early diagnosis of septic
      arthritis. MATERIAL AND METHODS: 82 patients were explored by ultrasonography for
      suspected septic arthritis. Mean age was 7 years (range 2 months to 37 years).
      All sonographic studies were performed using a 7.5 MHZ transducer. 52 patients
      were surgically treated or had joint aspiration. Only 39 patients had septic
      arthritis. The hip and the knee were the most frequent localisation (respectively
      20 and 12 cases). RESULTS: Statistical analysis showed that the ultrasound
      scanning in the diagnosis of joint effusion had a sensitivity of 93.4 per cent
      and a specificity of 100 per cent. Matter floating within the joint effusion was
      noted in 50 per cent of septic arthritis. These changes were not found in other
      arthritis. The thickness of synovialis and joint capsule was not specific of
      septic arthritis. In hip septic arthritis (51 per cent of localisation) the mean
      width of the anterior synovial recess was 11.7 mm (5-20 mm). In the asymptomatic
      opposite hip, the mean width was 3.6 mm (2.6-5 mm). Cortical irregularities had
      suggested osteomyelitis of femoral neck in osteoarthritis of the hip in 4 cases.
      Subperiosteal abscess of the femoral neck was directly visualized in another
      patient. DISCUSSION AND CONCLUSION: Our expense highlights that sonography may be
      a useful tool in the management of patient with suspect septic arthritis.
      Sonography allows early diagnosis of joint effusion with high accuracy.
      Hyperechoic or mixed aspects of the fluid joint suggest septic origin.

PMID- 9231183
TI  - [Value of a synthetic osseous model obtained by stereo-lithography for
      preoperative planning. Correction of a complex femoral deformity caused by
      fibrous dysplasia].
AB  - PURPOSE OF THE STUDY: The authors investigated the application of life-sized bone
      models obtained by stereolithography in orthopaedics. MATERIALS: The method was
      applied to planify correction of a severe femoral bone deformity secondary to
      fibrous dysplasia in a 27 years old man. This deformity was responsible for
      abnormal hip range of motion 70 degrees/-10 degrees (flexion-extension), -20
      degrees/60 degrees (abduction-adduction), -30 degrees/60 degrees (external
      internal rotation), and restricted walking ability because of lack of abduction
      and external rotation. A "shepherd-cross" deformity was identified on X-rays. A
      correction osteotomy was considered but we were unable to planify the angle of
      osteotomy on plain X-rays. CT scan identified 100 degrees of varus cervical
      deformity and 90 degrees of cervical antetorsion, but CT scan was helpless to
      choose the position for the osteosynthesis device. METHODS: 2D pictures obtained
      by CT scan were introduced and treated on a Silicon Graphics Indigo2 hardware.
      Mimics software authorized 2D and 3D views of bone which were separated of soft
      tissue by color separation process. CTM software authorized the 3D bone surface
      reconstruction (3D files). The 3D files were used to obtain life-sized bone model
      in 6 hours by stereolithographic process (scale 1/1). RESULTS: We planified a 70
      degrees valgus and 40 degrees derotation and chose the best location for
      osteosynthesis device considering the fibrous dysplasia (best location was the
      posterior and superior aspect of the femoral neck). The planified osteotomy was
      performed and we obtained the stability of a nail-plate in the femoral neck.
      During surgery, we observed the bone model and the deformed femur had the same
      shape. Likewise, the model strongly indicated the inside bone structure (ie
      distribution of fibrous dysplasia tissue). Bone healing was obtained after 5
      months with improvement of range of motion [(70/0) (20/30) (30/20)]. Histologic
      examination diagnosed fibrous dysplasia without malignancy features. CONCLUSION:
      Computer-generated life-sized bone models are available from computer tomographic
      data by means of stereolithographic process. This technic was helpful to improve
      planification of this complex proximal femoral osteotomy. Obtaining life-sized
      bone models could improve preoperative planning in case of multidirectional
      deformity, unusual site for osteotomy, or severe deformity impairing the choice
      for fixation device or its position into bone extremities. The indications for
      this method should be restricted to unusual and severe bone deformities, with
      inadequate preoperative assessment by standard X-rays or CT scans. Likewise, this
      method could be indicated for preoperative planning of technically demanding
      osteotomies such as oblique plane.

PMID- 9231184
TI  - [Malignant transformation of multiple chondroma. Apropos of a case].
AB  - Malignant transformation of multiple chondromas observed in Ollier's disease is a
      well known possibility. In the clinical case of a 52 year old woman reported
      here, the sarcomatous transformation of two endochondromatous foci occurred
      successively in less than one year. One was located in the calcaneus, the other
      within the proximal metaphysis of the ipsilateral fibula. This case is worth
      reporting for two reasons: the successive occurrence of these sarcomatous lesions
      led to a amputation below the knee, later completed by an extended radical
      resection of the fibula. This combination allowed to preserve the knee with a
      good functional result and without local recurrence, this clinical case may be
      compared with that reported by Goodman in 1984. Both cases show that sarcomatous
      transformations may occur almost simultaneously after a long quiscent period and
      suggest the existence of a factor that could trigger or favor a malignant
      transformation process.

PMID- 9231185
TI  - [Pigmented villonodular synovitis of the wrist. Apropos of a case].
AB  - The authors presented a case of pigmented villonodular synovitis of the wrist
      with extrinsic bony defects on opposing articular surfaces, seen after two
      recurrences following excision surgery. They performed a total synovectomy
      followed by curettage and autogenous bone grafting of the carpal and radiocubital
      bone lesions. Four years after the procedure, the patient-a woman aged 44-was
      symptom-free and there was no objectivable evidence of recurrence. Pigmented
      villonodular synovitis (PVNS) is an uncommon, benign, chronic process that causes
      synovial proliferation. Its etiology is unknown. The majority of patients is
      young to middle-aged adults. Especially the knee but other joints are involved
      including the hip, ankle, wrist, hand, and foot. Both soft tissue and bone
      abnormalities occur in PVNS. Magnetic resonance imaging (MRI) shows a
      heterogenous synovial mass with intermediate and low signal intensity areas on T1
      and T2-weighted images, consistent with hemosiderin deposition. Computed
      tomography defines clearly the extrinsic bone erosions and excavations, which
      usually exhibit a sclerotic margin, produced by intraosseous invasion of the
      expanding synovia. After excision recurrence is common, leading eventually to
      arthrodesis, arthroplasty and even radiation therapy. The etiology of PVNS is
      controversial. First approach is conservative surgical treatment with total
      synovectomy and curettage of the osteolytic foyers. Bone grafts are employed for
      filling the sites of osteolysis. The sensitivity of MRI permits early detection
      of the process and may obviate the need for radical management options in PVNS.

PMID- 9231186
TI  - TB or not TB?
AB  - These 3 cases illustrate what we believe to be unusual presentations of
      tuberculosis. In no case was there conclusive proof of infection with
      Mycobacterium tuberculosis using histological, microbiological or radiological
      techniques. All were treated empirically with anti-tuberculous medication, with
      complete recovery. With the re-emergence of tuberculosis, there may be a rise in
      such cases, and the importance of their recognition and empirical treatment is
      discussed.

PMID- 9231187
TI  - Assessment of cochlear damage after pneumococcal meningitis using otoacoustic
      emissions.
AB  - Three cases are reported of children in Ghana with pneumococcal meningitis and
      differing degrees of hearing loss. The children were examined up to 12 d after
      admission by means of otoacoustic emissions. The technique is objective, non
      invasive, quick (< 5 min per ear) and suitable for use in paediatric wards.

PMID- 9231188
TI  - Transmission and control of vivax malaria in Afghan refugee settlements in
      Pakistan.
AB  - Regular biting collections were conducted in 1993-1994 to investigate seasonal
      fluctuations in the abundance of anophelines in Afghan refugee villages in north
      western Pakistan. Enzyme-linked immunosorbent assay were used to test heads-plus
      thoraces for the presence of malaria sporozoites. Anophelines giving positive
      results for Plasmodium vivax were captured in every month except January. Nine
      species were positive. Biting rates showed a marked increase in May, after the
      spring rains, and thus spring transmission of vivax malaria seems certain.
      However, transmission of vivax malaria reached its peak only after the monsoon in
      July. To determine the optimal time to control vivax malaria by indoor spraying
      with residual insecticide, spray campaigns were conducted in either spring or
      summer in 14 refugee villages. Villages sprayed in July 1994 showed a mean
      reduction in annual incidence of 62% (95% confidence interval [CI] +/-6%)
      relative to the previous year, whereas villages sprayed in April 1994 showed only
      a 15% reduction (95% CI +/- 32%). Parasite prevalence surveys conducted in April
      and October 1994 confirmed the greater efficacy of spray campaigns waged in July.
      The insecticide malathion proved as effective as the pyrethroid
      lambdacyhalothrin, even though several species of anopheline were resistant to
      malathion.

PMID- 9231189
TI  - The epidemiology of severe malaria in an area of low transmission in Thailand.
AB  - The predisposing factors, clinical presentation, and outcome of severe malaria in
      a Karen community living on the western border of Thailand were studied over a
      period of 2 years. This was an area of low malaria transmission (approximately
      one infection per person per year), where asymptomatic malaria is unusual. In a
      population of 4728 persons, who had good access to facilities for malaria
      diagnosis and treatment, there were 2573 cases of vivax malaria, none of whom
      died, and there were 5776 cases of falciparum malaria, 303 (5%) of whom had
      severe malaria and 11 (0.2%) of whom died-a case fatality rate of 1.9 per 1000
      (95% confidence interval [CI] 1.0-3.3). The risks of developing severe malaria
      and dying declined steadily with age. The clinical features of severe malaria
      differed between children and adults. Anaemia was more common in children under 5
      years old than in older children and adults, whereas the incidence of cerebral
      involvement increased with age. Severe malaria was 3 times (95% CI 1.4-6.2) more
      common in pregnant than in non-pregnant women, but was 4.2 times (95% CI 2.3-7.9)
      less common in patients with mixed Plasmodium falciparum and P. vivax infections
      than in those with P. falciparum alone, suggesting that P. vivax may attenuate
      the severity of P. falciparum malaria.

PMID- 9231190
TI  - Epidemiological and genetic observations on human schistosomiasis in Kinshasa,
      Zaire.
AB  - A survey for Schistosoma intercalatum conducted in Kinshasa, Zaire, in September
      1994 revealed a prevalence of 3.6% (n = 167). Three isolates of schistosomes were
      made by exposing Bulinus wrighti to miracidia hatched from eggs collected from 2
      infected children. Characterization of the isolates by biochemical (isoenzymes of
      phosphoglucomutase), molecular (restriction fragment length polymorphism and
      randomly amplified polymorphic deoxyribonucleic acid analysis) and morphological
      (egg measurements) techniques confirmed the existence of an autochthonous
      transmission focus of S. intercalatum in Kinshasa. The study also provided
      evidence of the occurrence of natural hybridization between S. intercalatum and
      S. haematobium. No potential snail host for either species was found in the 2
      rivers examined. Apart from Bu. globosus from Zambia and Bu. wrighti, snail
      infection experiments showed an incompatible relationship between the parasite
      isolates and snails belonging to the Bu. forskalii group, the Bu. iruncatus/Bu.
      tropicus complex, and the Bu. africanus group.

PMID- 9231191
TI  - The distribution of Necator americanus and Ancylostoma duodenale among
      schoolchildren in Lagos, Nigeria.

PMID- 9231192
TI  - Hepatitis C antibody prevalence in blood donors in different governorates in
      Egypt.
AB  - Markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were
      sought in serum samples from 2644 blood donors in 24 of Egypt's 26 governorates.
      Of the 2644 samples, 656 (24.8%) were shown to contain anti-HCV immunoglobulin G
      antibody by Abbott second generation enzyme immunoassays (EIA). Of 85 EIA
      positive samples tested by recombinant immunoblot assay, 72 (85%) were positive.
      HCV seroprevalence in the governorates ranged from zero to 38%; 15 governorates
      (62%) had an HCV antibody prevalence greater than 20%, and 6 (25%) greater than
      30%. Governorates with higher sero-prevalences were located in the central and
      north-eastern Nile river delta, and south of Cairo in the Nile river valley.
      Subjects from areas in and adjoining the Sinai peninsula, in the eastern and
      western desert, and in southernmost Egypt, had the lowest prevalence of HCV
      antibody. The large urban governorates of Cairo and Alexandria had antibody
      prevalences of 19% and 11%, respectively. A total of 39.4% subjects had evidence
      of HBV infection (and-HBV core antigen total antibody). HCV infections were
      detected more frequently in donors with markers for HBV infections than in
      uninfected subjects (36% versus 18%, P < 0.001).

PMID- 9231194
TI  - Comparative evaluation of four techniques for the diagnosis of Plasmodium
      falciparum infections.
AB  - Four diagnostic techniques for Plasmodium falciparum infection were evaluated
      against serial parasite dilutions and on identical field samples. These were (i)
      Giemsa-stained thick blood films (GTF), (ii) acridine orange-stained thick (AOTF)
      and thin (AOTnF) blood films, (iii) the quantitative buffy coat technique (QBC);
      and (iv) the ParaSight-F dipstick test (PS). PS had a consistently higher
      sensitivity and speed, was easiest to learn, and required no laboratory facility.
      The 100% sensitivity cut-off points against known parasite densities (per mm3)
      were: PS, 30; GTF, 84; QBC, 84; AOTnF, 84; AOTF, 149. In the field study, test
      sensitivities compared with examination of 800 microscope fields of a Giemsa
      stained thin blood film were PS, 96.6%; AOTF, 93.1%; GTF, 91.4%; QBC, 89.7%;
      AOTnF, 82.8%. In the dilution study, one false positive result was recorded with
      QBC; in the field study there was one false positive each with PS, AOTnF and
      AOTF. When a newly trained microscopist examined samples of the parasite
      dilutions, the 100% sensitivity cut-off points were AOTF, 84; GTF, 140; QBC, 390.
      Total handling time was shortest with PS regardless of whether samples were
      processed individually or in batches of 10 or 100. The ParaSight-F test is
      recommended as the diagnostic tool for the future.

PMID- 9231193
TI  - Crimean-Congo haemorrhagic fever virus infection in the western province of Saudi
      Arabia.
AB  - In 1990, an outbreak of suspected viral haemorrhagic fever involving 7
      individuals occurred in Mecca in the Western Province of Saudi Arabia. Congo
      Crimean haemorrhagic fever (CCHF), not previously known to be present in Saudi
      Arabia, was incriminated. A study of the epidemiology of this virus was therefore
      carried out in Mecca, and in nearby Jeddah and Taif in 1991-1993; 13 species of
      ixodid ticks (5 Hyalomma spp., 5 Rhipicephalus spp., 2 Amblyomma spp., 1
      Boophilus sp.) were collected from livestock (camels, cattle, sheep, goats), and
      of these 10 were capable of transmitting CCHF. Camels had the highest rate of
      tick infestation (97%), and H. dromedarii was the commonest tick (70%). Attempts
      to isolate virus from pools of H. dromedarii and H. anatolicum anatolicum were
      unsuccessful. The source of infection in 3 confirmed cases of CCHF was contact
      with fresh mutton and, in a suspected case, slaughtering sheep. An investigation
      in Mecca, which included a serological survey of abattoir workers, identified 40
      human cases of confirmed or suspected CCHF between 1989 and 1990, with 12
      fatalities. Significant risk factors included exposure to animal blood or tissue
      in abattoirs, but not tick bites. It is suspected that the CCHF virus may have
      been introduced to Saudi Arabia by infected ticks on imported sheep arriving at
      Jeddah seaport, and that it is now endemic in the Western Province.

PMID- 9231195
TI  - Detection and characterization of Leishmania in tissues of patients with post
      kala-azar dermal leishmaniasis using a specific monoclonal antibody.
AB  - Sections from skin lesions and draining lymph nodes of patients with post kala
      azar dermal leishmaniasis were examined using an immunoperoxidase method and a
      monoclonal antibody directed against Leishmania donovani. Parasites were detected
      in 22 of 25 biopsies (88%). In parallel sections stained by haematoxylin and
      eosin, parasites were detected in only 5 of 25 of the biopsies (20%). The
      demonstration of whole parasites or parasite antigen is diagnostic.

PMID- 9231197
TI  - Detection of urinary schistosomiasis in a low prevalence region.

PMID- 9231198
TI  - An enzyme-linked immunosorbent assay using Schistosoma mansoni purified egg
      antigen for the diagnosis of schistosomiasis in Saudi Arabia.
AB  - The enzyme-linked immunosorbent assay (ELISA) using purified Schistosoma mansoni
      egg antigen (CEF6) was compared with standard parasitological diagnostic tests
      (potassium hydroxide digestion of faeces and urine filtration) for diagnosis of
      schistosomiasis in humans in Saudi Arabia. Faecal, urine and finger-prick blood
      samples were collected from 2 groups of individuals of both sexes, aged 1-50
      years, in 2 areas in the western region of Saudi Arabia: 983 in a schistosomiasis
      endemic area (Al-Hijaz highlands) and 192 in a non-endemic area (Jeddah). In the
      non-endemic area, almost 90% of the blood samples gave optical density readings
      at 492 nm (OD) < 0.25. The mean OD in the schistosome endemic area (0.31) was
      much higher than in the non-endemic area (0.14). The prevalence of S. mansoni
      infection by faecal examination in the endemic area was 10.2% and the specificity
      and sensitivity of the ELISA using a cut-off OD of 0.25 were 55% and 90%,
      respectively. In the endemic area, there was a positive correlation between egg
      intensity and OD value. No S. haematobium was detected. In the non-endemic area,
      the specificity was 90%. The main reasons for false positive results may have
      been inapparent or cured S. mansoni infection.

PMID- 9231199
TI  - Bancroftian filariasis: long-term effect of the DEC provocative day test on
      microfilaraemia.
AB  - The diethylcarbamazine (DEC) provocative day test has been widely used for
      daytime diagnosis of Wuchereria bancrofti infections in areas where microfilariae
      exhibit nocturnal periodicity. Since DEC is also the primary drug for treatment
      of bancroftian filariasis, we examined the long term effect of the test on
      microfilaraemia in 2 groups of individuals receiving either 100 mg of DEC (n =
      51) or placebo (n = 20). The low dose of DEC had a significant therapeutic
      effect. One year after treatment, the geometric mean in-tensity of
      microfilaraemia was reduced by 86.1%, and 10.6% of the individuals were
      amicrofilaraemic. No significant reduction of microfilaraemia was observed in the
      placebo group. The results imply that the DEC provocative day test should not be
      used as a diagnostic tool in follow-up studies on microfilaraemias.

PMID- 9231200
TI  - Tuberculous lymphadenitis, a diagnostic problem in areas of high prevalence of
      HIV and tuberculosis.
AB  - The human immunodeficiency virus (HIV) epidemic is associated with a marked
      increase of tuberculosis cases. The influence of HIV on diagnostic methods for
      tuberculous lymphadenitis is less clear. In an environment of high HIV and
      tuberculosis prevalence in Blantyre, Malawi, a prospective study compared results
      of basic procedures diagnosing tuberculous lymphadenitis with the outcome of
      histology and/or culture. One hundred out-patients, aged 15-55 years, with extra
      inguinal lymphadenopathy not responding to general antibiotics, entered the
      study. Among 52 cases, with whom all procedures were carried out in accordance
      with the protocol, 38 (73%) were diagnosed as tuberculous lymphadenitis; 84% of
      the latter (32/38) were seropositive for HIV. Needle aspirate and biopsy smears
      stained by the Ziehl-Neelsen technique contributed little to detecting
      tuberculosis, 8% and 11% respectively. In contrast, macroscopic caseation of
      excised lymph nodes showed a high yield of 82%, which was similar to histology,
      and higher than that of Lowenstein-Jensen culture (61%). The study suggested that
      HIV positivity of tuberculous lymphadenitis patients decreased the possibility of
      histology and culture both being indicative of tuberculosis (odds ratio 0.10; P =
      0.06). Consequently histology results, often used as the single definitive
      method, failed to diagnose 18% (7/38) of tuberculosis cases. However, it was
      reassuring that 4 simple methods, which can safely be carried out at district
      level, could be expected to diagnose 80-95% of tuberculous lymphadenitis cases in
      a timely and cost-effective manner.

PMID- 9231201
TI  - Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with
      malaria.
AB  - Nitric oxide is an important host defence molecule as well as being a mediator in
      many pathophysiological processes. To investigate its role in severe malaria, we
      measured plasma nitrate and nitrite concentrations in 70 children with malaria
      (54 with severe malaria) and 48 control subjects (33 with medical conditions and
      15 surgical patients). We related these measurements to plasma lactate
      concentrations, an established marker of disease severity in malaria. Plasma
      lactate levels were significantly elevated in patients with deep coma (P =
      0.0007) and those with a fatal outcome, but mean nitrogen oxide concentrations
      were not significantly different in the 2 outcome categories and were not related
      to depth of coma (P > 0.5). In patients whose cerebrospinal fluid (CSF) was
      examined, lactate concentrations were elevated in fatal cases (geometric mean 8.2
      mmol/L, n = 5) compared with survivors (3.4 mmol/L, n = 13; P = 0.032);
      corresponding CSF nitrogen oxide concentrations were 10.7 microM in fatal cases
      compared with 12.5 microM in survivors (P = 0.5). Plasma nitrogen oxide
      concentrations were negatively correlated with admission parasitaemia (r = -0.41,
      n = 70; P < 0.0001). In our population, elevations of plasma lactate, but not
      nitrite or nitrate, reflected disease severity in malaria.

PMID- 9231202
TI  - Serum creatinine levels and reactive nitrogen intermediates in children with
      cerebral malaria in Papua New Guinea.
AB  - Serum from 41 of 92 children admitted to Madang Hospital, Papua New Guinea, with
      cerebral malaria, previously assessed for serum levels of reactive nitrogen
      intermediates (RNI: nitrate plus nitrite), were re-assessed for creatinine levels
      on the day of admission. Further analysis of RNI levels on day 21 compared to day
      0 was carried out. Children with the highest RNI levels on admission, and with
      the longest duration of coma, did not have elevated creatinine levels. The
      highest levels of creatinine occurred among those with the lightest coma and
      creatinine levels were similar in those with short (< 48 h) and long (> 48 h)
      duration of coma. Between days 0 and 21, RNI decreased in 30 of 57 children,
      increased in 23, and did not change in 4. There was a significant relationship
      between the decrease in RNI relative to the level of RNI on admission and the
      duration of coma. For children with a coma duration < 48 h (48/57), there was no
      difference between the numbers showing an increase or a decrease in RNI level,
      but 6 of the 9 children with coma duration > 48 h showed a decrease in RNI
      greater than 50% of the RNI levels on admission. None of these 9 children had
      elevated creatinine levels. Elevated RNI levels in severe cases were thus not
      associated with renal function in these children in Papua New Guinea.

PMID- 9231203
TI  - Changes in procalcitonin and interleukin 6 levels among treated African patients
      with different clinical forms of malaria.

PMID- 9231204
TI  - Ultrasonography of periportal fibrosis in schistosomiasis mansoni in Brazil.
AB  - In patients with hepatosplenic schistosomiasis, characteristic thickening of the
      walls of the portal vein in the hilus and its central and peripheral branches is
      observed. In an area of high prevalence of the disease in Brazil, 424 individuals
      older than 5 years have been examined by abdominal ultrasonography and 146
      presented fibrosis, classified as central in 31 (21%), peripheral in 56 (38%),
      and both central and peripheral in 59 (40%). The mean ages of the subjects in the
      3 groups were 45.7, 24.1 and 31.9 years, respectively (P < 0.05). The presence of
      central fibrosis was associated with the presence of peripheral fibrosis (odds
      ratio 10.7, P < 0.000001). Splenomegaly was found in 16% and 15% of individuals
      with peripheral and both central and peripheral fibrosis, respectively. No
      subject with central but no peripheral fibrosis and splenomegaly was identified.
      We conclude that central fibrosis occurs among older subjects but should not be
      considered a criterion for advanced disease.

PMID- 9231205
TI  - Specific liver autoreactivity in schistosomiasis mansoni.
AB  - To investigate the possible involvement of autoimmune mechanisms in the
      development of hepatosplenic schistosomiasis (HSS), 234 patients with chronic
      Schistosoma mansoni infections were screened for a wide range of non-organ
      specific autoantibodies as well as for antibodies reacting with the GOR peptide
      and with a liver-specific autoantigen, the hepatic asialoglycoprotein receptor
      (ASGP-R). Thirty-five (15.0%) were seropositive for antinuclear, smooth muscle or
      gastric parietal cell antibodies at low titres (< or = 1:80), and 15/176 (8.5%)
      had anti-GOR, all of whom had concomitant hepatitis C viral (HCV) infections.
      Anti-ASGP-R was found in 64 (27.4%) of the 234 patients at titres similar to
      those found in 18 untreated auto-immune hepatitis patients studied concurrently.
      Anti-ASGP-R seropositivity occurred significantly (P < 0.005) more frequently in
      patients with HSS (62/190, 32.6%) than in those with hepatointestinal
      schistosomiasis (2/44, 4.5%), but did not correlate with severity of liver
      disease or with the presence of the non-organ-specific autoantibodies. Anti-ASGP
      R was found significantly (P < < 0.0005) less frequently in HSS patients who had
      had a splenectomy for portal hypertension (5/86, 5.8%) than in those who had not
      had a splenectomy (57/104, 54.8%). The findings suggest that liver-specific
      autoreactivity may play a role in the development of HSS.

PMID- 9231206
TI  - Onchocerciasis and reproductive health in Ecuador.
AB  - A retrospective study was performed comparing the number of spontaneous abortions
      in a hyperendemic area for onchocerciasis in Ecuador before and after invermectin
      treatment with that of a comparable non-endemic area. The frequency of
      spontaneous abortions was associated with a change in the community microfilarial
      load, suggesting that there may be a relationship between spontaneous abortions
      and infection with Onchocerca volvulus. In the endemic area, a significantly
      greater rate of spontaneous abortions was seen in the period before ivermectin
      distribution compared to that after the start of ivermectin treatments every 6
      months. In the non-endemic area, no change in the rate of spontaneous abortions
      was seen over the same time period. In addition to the well-documented
      improvements in skin and ocular disease, ivermectin may also improve the
      reproductive health of endemic populations.

PMID- 9231207
TI  - Nosocomial transmission of tuberculosis in Africa documented by restriction
      fragment length polymorphism.

PMID- 9231208
TI  - Snake bites in Kenya: a preliminary survey of four areas.
AB  - Primary data were collected on the incidence, severity and species responsible
      for snake bites in 4 areas of Kenya: (i) Kakamega and western Kenya, (ii) Lake
      Baringo and Laikipia, (iii) Kilifi and Malindi, and (iv) northern Kenya. The
      overall average frequency of snake bite was 13.8 per 100,000 population per year
      (range 1.9-67.9). The minimum rate of snake bite mortality was 0.45/100,000/year.
      Thirty-four of the 50 units visited reported no knowledge of death from snake
      bite in the last 5 years. Possible reasons for the low estimates are discussed.
      Traditional treatments were common, especially the use of herbal remedies and
      incisions at the wound site.

PMID- 9231209
TI  - Chlorproguanil/dapsone for uncomplicated Plasmodium falciparum malaria in young
      children: pharmacokinetics and therapeutic range.
AB  - The disposition of chlorproguanil/dapsone (one daily dose for 3 d of 1.2 and 2.4
      mg/kg respectively) has been studied in young children with Plasmodium falciparum
      malaria, to provide data complementary to a clinical trial of this drug
      combination. Unbound concentrations of chlorcycloguanil (the active metabolite of
      chlorproguanil) and dapsone in clinical samples have been related to the unbound
      drug concentrations which produced defined outcomes in tests in vitro of drug
      efficacy and toxicity. Twelve children with uncomplicated malaria were treated:
      all cleared parasitaemia within 72 h and made uneventful recoveries. After the
      first dose of chlorproguanil/dapsone the maximum unbound chlorcycloguanil
      concentration in clinical samples (19 ng/mL [about 60 nM]) was 2 orders of
      magnitude above the 50% inhibitory concentration (IC50) value for this drug
      against the K39 stain of P. falciparum, while falling 2 orders of magnitude below
      its IC50 against human bone marrow cells; the maximum unbound dapsone
      concentration in clinical samples (160 ng/mL [about 645 nM]) was 10-fold higher
      than its IC50 against the K39 strain. However, because of the rapid elimination
      of chlorproguanil from the body (half-life 12.6 +/- 6.3 h), the minimum
      fractional inhibitory concentrations of unbound chlorcycloguanil/dapsone against
      the K39 strain were probably exceeded for no more than 6 d. These data, together
      with the clinical trial, will be helpful in deciding whether current
      chlorproguanil/dapsone doses are optimal for the treatment of falciparum malaria.

PMID- 9231210
TI  - alpha, beta-Arteether for the treatment of complicated falciparum malaria.
AB  - alpha, beta-Arteether is an ethyl ether derivative of artemisinin which is an
      efficient schizontocidal drug in mild falciparum malaria. The present study
      reports the efficacy of the drug in severe falciparum malaria. Fifty patients
      with severe falciparum malaria were given intramuscular arteether, 150 mg, once
      daily on 3 consecutive days. The median fever clearance time was 72 h (range 12
      120 h) and the median parasite clearance time was 2 d (range 1-4 d). Rapid
      recovery from coma was observed in cerebral malaria patients (after a median of
      18 h, range 6-72 h). The recovery from other complications was also faster and
      complete. Two patients died; both had cerebral malaria and haemolytic jaundice,
      one had respiratory distress needing ventilatory support and the other had severe
      anaemia. Recrudescence within 28 d was observed in 7 patients. Drug toxicity or
      significant side effects were not noticed in any patient.

PMID- 9231212
TI  - Comparison of artemisinin suppositories, intramuscular artesunate and intravenous
      quinine for the treatment of severe childhood malaria.
AB  - Severe malaria remains a major cause of mortality and morbidity for children
      living in many tropical regions. With the emergence of strains of Plasmodium
      falciparum resistant to both chloroquine and quinine, alternative antimalarial
      agents are required. The artemisinin group of compounds are rapidly effective in
      severe disease when given by intramuscular or intravenous injection. However,
      these routes of administration are not always available in rural areas. In an
      open, randomized comparison 109 Vietnamese children, aged between 3 months and 14
      years, with severe P.falciparum malaria, were allocated at random to receive
      artemisinin suppositories followed by mefloquine (n = 37), intramuscular
      artesunate followed by mefloquine (n = 37), or intravenous quinine followed by
      pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4
      artesunate and 5 quinine-treated children. There was no difference in fever
      clearance time, coma recovery, or length of hospital stay among the 3 groups.
      However, parasite clearance times were significantly faster in artemisinin and
      artesunate-treated patients than in those who received quinine (P < 0.0001). Both
      artemisinin and artesunate were very well tolerated, but children receiving these
      drugs had lower peripheral reticulocyte counts by day 5 of treatment than those
      in the quinine group (P = 0.011). No other adverse effect or toxicity was found.
      There was no treatment failure in these 2 groups, but 4 patients in the quinine
      group failed to clear their parasites within 7 d of starting treatment and
      required alternative antimalarial therapy. Artemisinin suppositories are easy to
      administer, cheap, and very effective for treating children with severe malaria.
      In rural areas where medical facilities are lacking these drugs will allow
      antimalarial therapy to be instituted earlier in the course of the disease and
      may therefore save lives.

PMID- 9231213
TI  - Prevention and morbidity of malaria in non-immune subjects; a case-control study
      among Italian troops in Somalia and Mozambique, 1992-1994.
AB  - The impact of malaria on Italian troops taking part in 1992-1994 in the United
      Nations Organization humanitarian missions in Somalia and Mozambique is
      discussed. In Somalia, 18 cases of Plasmodium falciparum malaria occurred among
      11,600 soldiers; the overall attack rate was 0.4 cases/1000/month of exposure and
      the risk of malaria was effectively reduced by chemoprophylaxis with chloroquine
      plus proguanil (C+P) (odds ratio [OR] = 0.05, 95% confidence limits [95% CL] 0.02
      0.16). In Mozambique, 119 cases of P.falciparum malaria occurred among 4800
      soldiers; most cases (100) occurred in the first months of deployment (late March
      June 1993), with an attack rate of 17 cases/1000/month, when C+P was the
      recommended chemoprophylactic regimen; the remaining 19 cases occurred
      subsequently, with an attack rate of 1.8 cases/1000/month, after C+P was replaced
      by mefloquine in July 1993. Protection achieved by C+P was unsatisfactory (OR =
      0.37, 95% CL 0.21-0.67), while chemoprophylaxis with mefloquine effectively
      reduced the risk of malaria in Mozambique (OR = 0.03; 95% CL 0.01-0.10). A
      significant number of malaria infections was also detected among soldiers
      following their return home from Somalia (147 cases) and Mozambique (40 cases);
      these were due mainly to P. vivax. Fifteen of 113 P. vivax primary infections
      imported from Somalia (13.3%) relapsed 2-13 months after the primary attack.
      Because of the small proportion of relapsing P. vivax tropical strains,
      primaquine may be limited to radical treatment of relapses or, more extensively,
      of all P. vivax infections, but it should not be necessarily given to all
      asymptomatic subjects returning from tropical endemic areas, as is generally
      suggested for particular groups at risk.

PMID- 9231211
TI  - The disposition of intramuscular artemether in children with cerebral malaria; a
      preliminary study.
AB  - The disposition of intramuscular artemether (AM) was studied in 26 Kenyan
      children with cerebral malaria. Antimalarial activity determined by bioassay was
      compared with total plasma AM plus dihydroartemisinin (DHA) determined by high
      power liquid chromatography (HPLC). Therapeutic levels were achieved in most
      subjects (21/26) within 1 h of receiving intramuscular AM (3.2 mg/kg), with close
      correlation between bioassay and HPLC measurements (r = 0.706). However, there
      was marked inter-individual variation, antimalarial activity was undetectable in
      5 subjects ('non-absorbers'), and plasma concentrations were lower in subject
      with respiratory distress. The 50% parasite clearance time was significantly
      longer in non-absorbers (mean = 13.1 h, SD = 10.8 vs. mean = 7.8 h, SD = 5.5; P =
      0.013). We conclude that the bioavailability of intramuscular AM in children with
      severe malaria may be highly variable, particularly in the presence of
      respiratory distress, and may be associated with an inadequate therapeutic
      response.

PMID- 9231214
TI  - Short courses of ofloxacin for the treatment of enteric fever.
AB  - Typhoid fever continues to be a major public health problem in tropical
      countries, exacerbated in recent years by the spread of multi-drug resistant
      strains of Salmonella typhi. Short treatment courses of fluoroquinolones are
      effective, and have the advantage of reduced cost and increased compliance, but
      the optimal length of treatment is unknown. In an open, randomized comparison,
      107 adults with uncomplicated enteric fever (95 of whom had positive blood
      cultures for S. typhi and 5 for S. paratyphi) were treated with oral ofloxacin,
      15 mg/kg/d for 2 d or 10 mg/kg/d for 3 d. Mean fever clearance times were the
      same in the 2 treatment groups (97 h). There were 7 treatment failures, one in
      the 2 d group and 6 in the 3 d group (P = 0.07). Three of the 5 patients infected
      with nalidixic acid resistant strains of S. typhi had treatment failures,
      compared with 4 of 90 with nalidixic acid sensitive isolates (P < 0.0001;
      relative risk 13.5, 95% confidence interval 4.1-43%). Treatment with ofloxacin
      for 2 or 3 d is equally effective in adults with uncomplicated enteric fever
      caused by nalidixic acid sensitive strains of S. typhi. The epidemiology and
      management of nalidixic acid resistent typhoid needs further investigation.

PMID- 9231215
TI  - Human infection with Onchocerca volvulus does not affect the T helper cell
      phenotype of the cellular immune response to mycobacterial antigen.
AB  - In order to determine whether infection with Onchocerca volvulus might modify the
      immune response to mycobacterial antigen, the proliferative and cytokine
      responses of peripheral blood mononuclear cells from 117 persons infected with O.
      volvulus and 36 non-endemic control subjects were compared. Tuberculin-stimulated
      cellular proliferative responses and production of Th1-type cytokines (interferon
      gamma) were reduced in persons infected with O. volvulus compared to controls.
      However, there was no evidence of polarization of the immune response towards a
      Th2-type phenotype (interleukin 5) in infected individuals compared to controls.

PMID- 9231216
TI  - Molecular characterization of Bulinus globosus and B. nasutus on Zanzibar, and an
      investigation of their roles in the epidemiology of Schistosoma haematobium.
AB  - The ribosomal internal transcribed spacer (ITS) regions of both Bulinus globosus
      and B. nasutus from Zanzibar were amplified and restricted with 6 enzymes.
      Restriction products were separated by polyacrylamide gel electrophoresis and
      visualized by ethidium bromide staining. Considerable genetic variation was
      observed at 3 levels: (i) between species, (ii) among populations and (iii) among
      individuals. In addition, the 18S ribosomal deoxyribonucleic acid gene was
      amplified from both species and the products were also restricted with several
      enzymes. No variation was detected. Nucleotide diversity of the ITS was estimated
      to be approximately 0.019 for both species and nucleotide divergence between
      species was estimated to be 0.03. Restriction profiles differentiated these snail
      species and may prove useful for identification purposes. Only B. globosus
      populations were found to be naturally infected with Schistosoma haematobium.
      From laboratory infection studies of progeny snails, B. nasutus appeared to be
      refractory to S. haematobium, whereas certain B. globosus populations were
      susceptible to laboratory challenge.

PMID- 9231217
TI  - Ribotyping and DNA macrorestriction analysis of isolates of Burkholderia
      pseudomallei from cases of melioidosis in Malaysia.
AB  - Forty-nine isolates of Burkholderia pseudomallei from sporadic cases of
      melioidosis in Malaysia over the past 18 years were examined by BamHI ribotyping
      and pulsed-field gel electrophoresis (PFGE) of XbaI digests of total
      deoxyribonucleic acid (DNA). Twenty-four patients had septicaemic melioidosis
      with a mortality of 70%; mortality in the non-septicaemic disease was 16%. Five
      ribotype patterns were identified, 2 of which accounted for 90% of all isolates.
      PFGE revealed a number of different strains within these ribotypes, but some
      pairs of isolates from unrelated cases gave closely similar DNA profiles. These
      results are in agreement with Australian studies which showed a high prevalence
      of a few ribotypes of B. pseudomallei which are further divisible by genotyping,
      in areas where melioidosis is endemic.

PMID- 9231218
TI  - PCR amplification of DNA from malaria parasites on fixed and stained thick and
      thin blood films.
AB  - Under some circumstances, polymerase chain reaction (PCR) amplification of
      deoxyribonucleic acid (DNA) from Plasmodium may become necessary from infections
      for which only blood slides are available. Established methods used for DNA
      preparation do not work in that case. We have developed a reliable and controlled
      method for DNA preparation from malaria parasites on fixed and stained blood
      films. 162 slides from 2 different locations, some stored for at least one year,
      have been analysed by PCR amplification of the polymorphic loci for MSA1 and
      MSA2. In 92% of microscopically positive slides, a PCR product could be detected
      using material derived from thick blood films. When thin blood films with scanty
      parasitaemia were used, a PCR product could be obtained with only 71% of samples.
      In all unsuccessful cases, DNA preparation was the limiting factor, which was
      controlled for by amplification of a control human template.

PMID- 9231219
TI  - An alternative to serum for cultivation of Plasmodium falciparum in vitro.

PMID- 9231220
TI  - Possible health hazards from birds in the rural environment.

PMID- 9231221
TI  - Modified urine filtration to detect eggs of Schistosoma haematobium.

PMID- 9231222
TI  - The effect of an interrupted daily period of normal visual stimulation on form
      deprivation myopia in chicks.
AB  - The aim of this study was to determine whether an integrator of neural activity
      influences the amount of myopia and axial elongation resulting from deprivation
      of form vision. The effects on ocular parameters of a continuous period of 30 min
      per day of normal vision was compared to two exposures of 15 min duration each,
      or three exposures of 10 min each. For the remaining time, chicks had monocular
      translucent occlusion in a 12 hr light/12 hr dark diurnal cycle, for either 2 or
      3 weeks. Fellow eyes and the eyes of bilaterally unoccluded chicks were used as
      controls. We found that several short periods of normal visual stimulation per
      day were more effective in preventing the development of form deprivation myopia
      and axial elongation than was one single period of the same total duration, after
      both 2 and 3 weeks of treatment. This study suggests that the level of neural
      activity in the retina may have a cumulative effect in influencing ocular growth.

PMID- 9231223
TI  - Dependencies of motion assimilation and motion contrast on spatial properties of
      stimuli: spatial-frequency nonselective and selective interactions between local
      motion detectors.
AB  - Two sets of experiments were carried out to examine dependencies of two types of
      induced motion (motion assimilation and motion contrast) on spatial properties of
      stimuli in terms of spatial-frequency tuning of local motion detectors. In the
      first set, the magnitudes of motion assimilation and motion contrast for a
      sinusoidal grating were measured at a function of the spatial frequency of the
      inducing gratings, with the spatial frequency of the test grating as a parameter.
      In the second set, the magnitudes were measured as a function of the height of
      the inducing gratings with the spatial frequencies of the test and the inducing
      gratings as parameters. For motion assimilation, the magnitude was characterized
      by a low-pass function of the spatial frequency of the inducing gratings, and the
      critical height of the inducing gratings, which demarcates the extent of the
      spatial pooling, varied systematically depending on the spatial frequency of the
      inducing gratings. For motion contrast, on the other hand, the magnitude was
      characterized by a hand-pass function, and the critical height depended on the
      frequency of the test grating. These results suggest that motion assimilation is
      mediated by the spatial-frequency nonselective interaction between the local
      detectors, in which the motion signals of the detectors tuned to different
      spatial frequencies are integrated with each other. Motion contrast is mediated
      by the spatial-frequency selective interaction, in which the motion signals of
      the local detectors tuned to the same or similar spatial frequencies are compared
      and differentiated.

PMID- 9231224
TI  - Visual motion sensation yielded by non-visually driven attention.
AB  - When a visual stimulus (the "cue") is presented and followed by a line, the line
      is perceived to grow rapidly from the cued side even when it is presented
      physically simultaneously (the "line-motion effect"). We now report that the same
      line motion can be observed when the cue is presented in a non-visual modality,
      such as auditory or somatosensory. A beep sound was presented either from the
      left or the right speaker as an auditory cue, or an electric pulse was applied to
      a finger put on the left or the right side of a CRT display as a somatosensory
      cue. A line probe was then presented between the two possible cue positions. Both
      the auditory and the somatosensory cues led to line motion, thus the line motion
      could not be interpreted as a variation of within-modality effects, such as
      visual apparent motion. When the cue lead time was manipulated, the obtained time
      courses of the effects were similar across the three cue modalities (Experiment
      1). The minor differences could be explained simply in terms of latency of
      detection, according to results of another experiment (Experiment 2). Finally,
      the line-motion task was compared with a task of temporal order judgment, where
      two targets were presented simultaneously at the cued and the uncued sides, and
      the subject was asked to judge which of the targets had appeared first. As a
      result, similar dependencies on cue lead time were obtained between the two tasks
      within subjects (Experiment 3). Thus, the non-visual cue seems to facilitate
      "prior entry" of a visual stimulus nearby in the spatial representation, much the
      same way as a visual cue does. These effects should be attributed to modality non
      specific spatial attention, i.e., a "gradient" of information processing
      efficiency across various locations.

PMID- 9231225
TI  - Simultaneous color contrast in goldfish--a quantitative study.
AB  - A set of 9-15 colored test fields was presented to goldfish. In Experiment 1,
      test field hues ranged from green through yellow to red; in Experiment 2, the
      hues varied from blue through gray to yellow. In the training conditions, the
      test fields were presented with a gray or black surround. The fish learned to
      choose one intermediate test field hue by rewarding them with food. In the test
      conditions, the color of the surround was changed from gray to green, or red
      (Experiment 1), and from black to blue, or yellow (Experiment 2). The choice
      behavior of the goldfish changed substantially: one of the test fields other than
      the training test field was preferred. Direction and strength of simultaneous
      color contrast was quantified in goldfish color space. The effect of spatial
      stimulus configuration was investigated by changing test field size and using
      narrow annular surrounds. With test field radii ranging between 2 and 7.5 mm
      simultaneous color contrast was optimal whenever the ratio between surround width
      and test field radius had a value of about 1:1.

PMID- 9231226
TI  - Principles of an adaptive method for measuring the slope of the psychometric
      function.
AB  - Recent developments in the efficient estimation of threshold are here extended to
      the problem of how best to estimate the slope of the psychometric function. An
      adaptive method is described for selecting stimulus intensities that are optimal
      for slope estimation. A two-dimensional array of probabilities of different
      thresholds and slopes is used to calculate the stimulus intensity for the next
      trial; this array is updated after the trial, using Bayes' theorem to incorporate
      information from the subject's response. The practical implementation and
      efficiency of the method are demonstrated and discussed.

PMID- 9231227
TI  - The computation of binocular visual direction: a re-examination of Mansfield and
      Legge (1996)
AB  - Mansfield and Legge (1996) reported recently that a target's perceived binocular
      direction is dependent on the ratio of contrasts presented to the two eyes.
      Although their main conclusion concerned the dependence of perceived direction on
      interocular contrast, they also argued that the change in perceived direction is
      due to a shift in the position of the cyclopean eye and that the relative
      directions of binocular targets are unaffected by eye position. We take issue
      with both of these arguments. With regard to the former, their task was an
      alignment task, not an egocenter task, so it did not provide information relevant
      to the position of the cyclopean eye. Indeed, their data can be explained by the
      conventional theory of binocular visual directions with a fixed cyclopean eye
      (e.g., Hering, 1879; Ono, 1981) once a simple, but important modification is
      added. With regard to their conclusion concerning eye position, we show that the
      vergence of the eyes has a clear and systematic effect on perceived relative
      directions in the setup used by Mansfield and Legge.

PMID- 9231228
TI  - The early phase of horizontal optokinetic responses in the pigmented rat and the
      effects of lesions of the visual cortex.
AB  - Horizontal optokinetic responses of pigmented rats were studied both in intact
      animals and in animals that had received lesions of the visual area of the
      cerebral cortex. In response to uniform velocity stimulation, there was an
      initial phase of rapid acceleration, larger than that reported in earlier
      studies, followed by a period of fairly uniform acceleration until the eye
      velocity approached that of the stimulus. As reported previously, responses to
      monocular stimulation were highly asymmetric, with the responses to nasotemporal
      stimulation being much weaker than those to temporonasal stimulation. Responses
      to sinusoidal stimulation were also studied. No significant effect of cortical
      lesions on the responses was seen.

PMID- 9231229
TI  - Ocular responses to motion parallax stimuli: the role of perceptual and
      attentional factors.
AB  - When human subjects are presented with visual displays consisting of random dots
      moving sideways at different velocities, they perceive transparent surfaces,
      moving in the same direction but located at different distances from themselves.
      They perceive depth from motion parallax, without any additional cues to depth,
      such as relative size, occlusion or binocular disparity. Simultaneously, large
      field visual motion triggers compensatory eye movements which tend to offset such
      motion, in order to stabilize the visual image of the environment. In a series of
      experiments, we investigated how such reflexive eye movements are controlled by
      motion parallax displays, that is, in a situation where a complete stabilization
      of the visual image is never possible. Results show that optokinetic nystagmus,
      and not merely active visual pursuit of singular elements, is triggered by such
      displays. Prior to the detection of depth from motion parallax, eye tracking
      velocity is equal to the average velocity of the visual image. After detection,
      eye tracking velocity spontaneously matches the slowest velocity in the visual
      field, but can be controlled by attentional factors. Finally, for a visual
      stimulation containing more than three velocities, subjects are no longer able to
      perceptually dissociate between different surfaces in depth, and eye tracking
      velocity remains equal to the average velocity of the visual image. These data
      suggest that, in the presence of flow fields containing motion parallax,
      optokinetic eye movements are modulated by perceptual and attentional factors.

PMID- 9231230
TI  - Gaze stabilization by optokinetic reflex (OKR) and vestibulo-ocular reflex (VOR)
      during active head rotation in man.
AB  - Vestibulo-ocular reflex (VOR)-optokinetic reflex (OKR) interaction was studied in
      normal human subjects during active sine-like head movements in the horizontal
      plane for a variety of vestibular-optokinetic stimulus combinations (frequency
      range, 0.05-1.6 Hz). At low to mid frequencies (< 0.2 Hz) the eyes tended to be
      stabilized on the optokinetic pattern, independently of whether the head, the
      pattern, or both were rotated. At higher frequencies, the OKR gain was attenuated
      and, in each of the differing stimulus combinations, the eyes became increasingly
      stabilized in space. Qualitatively similar results were obtained when, for the
      same visual-vestibular combinations, the head was passively rotated at 0.05 and
      0.8 Hz. The data could be simulated by a model which assumes a linear interaction
      of vestibular and optokinetic signals. It considers the OKR with its negative
      feedback loop of primordial importance for image stabilization on the retina and
      the VOR only as a useful addition which compensates for the limited bandwidth of
      the OKR during high frequency/velocity head rotations in a stationary visual
      environment.

PMID- 9231231
TI  - Testing the Perrone and Stone (1994) model of heading estimation.
AB  - Human observers cannot judge heading accurately in the presence of simulated gaze
      rotations under many conditions [Royden et al. (1994). Vision Research, 34, 3197
      3214]. They make errors in the direction of rotation with magnitudes proportional
      to the rotation rate. Two hypotheses have been advanced to explain this
      phenomenon. The extra-retinal-signal hypothesis states that the observer's
      estimate of gaze rotation is always based on an extra-retinal signal such as an
      efference copy. In the absence of such a signal, the observer assumes that no
      rotation has taken place and responds accordingly. The retinal-image hypothesis
      states that visual input dominates when the extra-retinal signal is small or
      absent; under this hypothesis, errors with simulated rotations are the
      consequence of faulty visual mechanisms. Perrone and Stone [(1994). Vision
      Research, 34, 2917-2938] proposed a model that purports to account for these
      errors using retinal-image information (optic flow) alone; its assumptions make
      it inefficient under some conditions. The most important of these assumptions is
      that the fixated target is stationary with respect to the world (the gaze
      stabilization constraint). I compared the model's performance to human data from
      two experiments of Royden et al. [(1994). Vision Research, 34, 3197-3214]. One
      experiment simulated translation while tracking a target attached to the scene
      (gaze-stabilized), while the other simulated translation while tracking a target
      that was not attached (gaze-unstabilized). The incorporation of the gaze
      stabilization constraint leads to a predicted asymmetry for the errors in the
      gaze-unstabilized experiment that is not observed in human data. I conclude that
      the model as it stands is not consistent with human behavior. It is possible,
      however, that the predicted asymmetry is masked in human data by a counteracting
      asymmetry in a hypothetical processing stage subsequent to the heading estimation
      that extrapolates the observer's future path of self-motion.

PMID- 9231232
TI  - Becoming a "Greeble" expert: exploring mechanisms for face recognition.
AB  - Sensitivity to configural changes in face processing has been cited as evidence
      for face-exclusive mechanisms. Alternatively, general mechanisms could be fine
      tuned by experience with homogeneous stimuli. We tested sensitivity to configural
      transformations for novices and experts with nonface stimuli ("Greebles"). Parts
      of transformed Greebles were identified via forced-choice recognition. Regardless
      of expertise level, the recognition of parts in the Studied configuration was
      better than in isolation, suggesting an object advantage. For experts,
      recognizing Greeble parts in a Transformed configuration was slower than in the
      Studied configuration, but only at upright. Thus, expertise with visually similar
      objects, not faces per se, may produce configural sensitivity.

PMID- 9231233
TI  - A physiological model for motion-stereo integration and a unified explanation of
      Pulfrich-like phenomena.
AB  - Many psychophysical and physiological experiments indicate that visual motion
      analysis and stereoscopic depth perception are processed together in the brain.
      However, little computational effort has been devoted to combining these two
      visual modalities into a common framework based on physiological mechanisms. We
      present such an integrated model in this paper. We have previously developed a
      physiologically realistic model for binocular disparity computation (Qian, 1994).
      Here we demonstrate that under some general and physiological assumptions, our
      stereo vision model can be combined naturally with motion energy models to
      achieve motion-stereo integration. The integrated model may be used to explain a
      wide range of experimental observations regarding motion-stereo interaction. As
      an example, we show that the model can provide a unified account of the classical
      Pulfrich effect (Morgan & Thompson, 1975) and the generalized Pulfrich phenomena
      to dynamic noise patterns (Tyler, 1974; Falk, 1980) and stroboscopic stimuli
      (Burr & Ross, 1979).

PMID- 9231234
TI  - Hepatic retinopathia. Changes in retinal function.
AB  - In patients suffering from hepatic failure, the brain is subject to defined
      morphological and functional changes known as hepatic encephalopathia (HE). The
      morphological changes are dominated by glial cells (Alzheimer-type II
      astrocytes). It has recently been possible to demonstrate, that the retinal glia
      (Muller) cells undergo similar morphological changes. The present study was
      carried out in order to reveal if these Muller cell changes cause any
      characteristic functional deficits. We examined 11 patients with different stages
      of HE due to liver cirrhosis. Six patients were at stage 0 or 1 (group I) and
      five at stage 2 or 3 (group II). They underwent ophthalmological routine
      examination, colour vision testing and standard ERG recording. None of the
      patients reported impaired vision, in daylight or at night. There were no fundus
      abnormalities except very mild changes of the pigment epithelium and abnormal
      reflexes of the inner limiting membrane, especially in the higher HE stages. The
      number of confusions in the colour arrangement test increased with the higher
      stages of HE, preferably in the tritan axis. The scotopic a- and b-waves of the
      electroretinogram (ERG) were almost unchanged in group I and significantly
      decreased and delayed in group II. The photopic ERG b-wave amplitudes were
      changed in a similar fashion. Oscillatory potentials proved to be most sensitive
      to hepatotoxic changes. Their latencies were significantly delayed even in group
      I. Amplitudes were decreased significantly only in group II. Patients suffering
      from hepatic failure and accompanying HE display functional abnormalities of the
      retina. These are best demonstrated by the ERG, and correlate well with the
      degree of HE. A hypothesis is presented that relates the observed functional
      changes to altered neurotransmitter levels and impaired retinal glial-neuronal
      interaction, due to Muller cell damage caused by elevated ammonia levels.

PMID- 9231235
TI  - Influence of varied progestogen treatments on ovarian follicle status and
      subsequent ovarian superstimulatory responses in cows.
AB  - The influence of ovarian follicle status and follicle dominance on the response
      to superstimulatory treatment with FSH was examined in cows. In Experiment 1,
      oestrus was synchronised using Crestar and on Days 4-6 of the ensuing oestrous
      cycle cows were assigned to: Group NO (n = 9), control, endogenous CL and no
      treatment; Group N1 (n = 15), injected with a luteolytic dose of cloprostenol
      (500 micrograms) and implanted with one implant (3 mg) of the synthetic
      progestogen, norgestomet; Group N8 (n = 18), injected with 500 micrograms
      cloprostenol and implanted with eight (24 mg) implants of norgestomet. On Days 9
      11, seven implants were removed from six cows in Group N8 and these cows, plus
      eight Group N1 and all Group N0 cows, were superstimulated with porcine FSH
      (Folltropin-V) over 4 days (360 mg total dose). The remaining implants were
      removed from cows in Groups N1 and N8 on Days 11-13, and all cows received 500
      micrograms cloprostenol. Numbers and sizes of ovarian follicles, and CL, were
      recorded by trans-rectal ultrasonography; the largest follicle > 10 mm in
      diameter was considered morphologically dominant (DF). On Days 9-11, the
      proportions of cows with a DF were: Group N0, 3/9; Group N1, 14/15; Group N8,
      0/18. Total follicles on the 4th day of FSH treatment were greater (P < 0.05) for
      cows in Group N1 (21.6 +/- 4.2) compared with Group N0 (10.9 +/- 2.4), with cows
      in Group N8 (13.2 +/- 0.9) not different from the other two groups. Subsequent
      numbers of CL were lower (P < 0.05) for cows in Group N1 (5.0 +/- 1.3) compared
      with Group N0 (9.4 +/- 2.0), with cows in Group N8 (8.5 +/- 1.0) not different
      from the other two groups. In Experiment 2, oestrus was synchronised in cows and
      on Days 4-6, cows were assigned to: Group C0 (n = 7), control, endogenous CL and
      no treatment; Group C3 (n = 6), received three CIDR-B intra-vaginal devices that
      delivered progesterone. On Days 9-11, two CIDR-B were removed from cows in Group
      C3 and all cows treated with FSH as in Experiment 1. The remaining CIDR-B was
      removed from cows in Group C3 on Days 11-13 and all cows injected with 500
      micrograms cloprostenol. Proportions of cows with a DF on Days 9-11 and diameter
      of largest follicle were: Group C0, 6/7 and 12.6 +/- 0.9 mm; Group C3, 2/6 and
      9.6 +/- 0.8 mm. Numbers of CL on Day 8 after oestrus were: Group C0, 20.0 +/-
      7.1; Group C3, 14.8 +/- 4.8 (P > 0.05). Exposure to low dose norgestomet allowed
      development of a persistent dominant follicle, resulting in a reduced response to
      superstimulation with FSH. High dose progestogen restricted follicle growth
      without apparent effects on responses to superstimulation.

PMID- 9231236
TI  - Contribution of the scrotum, testes, and testicular artery to scrotal/testicular
      thermoregulation in bulls at two ambient temperatures.
AB  - The objective of this study was to determine the contribution of the scrotum,
      testes, and the testicular artery to scrotal/testicular thermoregulation in bulls
      at two ambient temperatures. Crossbred beef bulls, 1.5 years of age, were placed
      in controlled environment chambers at ambient temperatures of 15 degrees C (n =
      5) or 25 degrees C (n = 6). The distal lateral aspects and entire ventral part of
      the scrotum was incised under caudal epidural anaesthesia (xylazine, 0.07 mg kg
      1. Both testes were withdrawn from the scrotum and then replaced and maintained
      by clamping the scrotal incisions with towel clamps. One testis was randomly
      chosen to be the exposed testis and was withdrawn prior to temperature
      measurements. Surface and internal temperature were measured with infrared
      thermography and needle thermocouples, respectively. Temperature gradients
      (degree C; difference in temperature from top to bottom at 15 and at 25 degrees
      C) were: scrotal surface (with testis), 1.5 and 1.3; scrotal surface (without
      testis), 2.1 and 1.6; surface of exposed testis, -0.6 and 0.0; sub-tunic of
      exposed testis, -2.2 and -0.6; intratesticular (covered testis), 0.0 and 0.4; and
      intratesticular (exposed testis), -1.3 and 0.4. The scrotum markedly affects
      testicular temperature but the testes have limited influence on scrotal surface
      temperature. The bovine scrotum and testes have opposing temperature gradients
      that complement one another, resulting in a relatively uniform intratesticular
      temperature. These temperature gradients are attributed in part to the testicular
      artery, which goes from the top of the testis to the bottom, divides into several
      branches and ramifies dorsally and laterally before entering the testicular
      parenchyma. Intra-arterial temperatures (measured with needle thermocouples) were
      lower (P < 0.05) where the artery entered the testis than at both the bottom and
      top of the testis for both the covered (31.7, 33.4 and 34.3 degrees C) and
      exposed testis (29.6, 32.0 and 32.5 degrees C) at an ambient temperature of 15
      degrees C. Temperature differences were similar, but less pronounced, at 25
      degrees C (covered testis, 34.8, 36.3 and 36.5 degrees C; exposed testis, 32.4,
      33.5, 33.9 degrees C). Results supported the hypothesis that blood within the
      testicular artery has a similar temperature at the top of the testis (just
      ventral to the testicular vascular cone) compared with the bottom, but
      subsequently cools before entering the testicular parenchyma.

PMID- 9231237
TI  - The effects of neurotransmitter antagonists and glucose on luteinizing hormone
      secretion in growth-restricted wethers.
AB  - Chronic undernutrition results in reduced secretion of luteinizing hormone (LH).
      Two experiments were conducted in wethers whose LH secretion was suppressed by
      growth restriction caused by feeding a maintenance ration. The first study
      examined neurotransmitters that may be actively inhibiting LH secretion during
      growth restriction. The effects of various neurotransmitter antagonists were
      investigated: pimozide (PIM, dopamine), cyproheptadine (CYP, serotonin),
      pyrilamine (PYR, H1), cimetidine (CMT, H2) and propranolol (PRO, beta-adrenergic)
      in wethers specifically fed to maintain a body weight of 28 kg (GR, n = 7) and in
      full fed control wethers (n = 5). Blood samples were taken at 15 min intervals
      for 4 h before and after drug administration. Serum LH concentrations were
      determined by radioimmunoassay (RIA). Only PIM increased (P < 0.01) serum LH
      pulse frequency in the GR wethers (pre 0.5 +/- 0.2 pulses per 4 h vs. post 2.6 +/
      0.9 pulses per 4 h). None of the drugs tested had an effect on the control
      wethers. Experiment 2 examined the effect of glucose administration (50, 100, or
      150 mg i.v.) on LH secretion in GR wethers. Only the 150 mg dose significantly (P
      < 0.05) increased LH pulse frequency compared to the pre-injection period (1.1 +/
      0.3 vs. 2.0 +/- 0.4 pulses per 4 h). After refeeding, LH pulse frequency and
      serum glucose concentrations increased. Proglumide, a cholecystokinin (CCK)
      antagonist, did not block this increase (2.1 +/- 0.4 vs. 2.2 +/- 0.3 pulses per 4
      h). These data suggest that dopamine inhibits LH secretion in GR wethers and that
      increasing serum glucose concentrations increased LH secretion.

PMID- 9231238
TI  - The circulating concentrations of FSH, LH and prolactin in the oestradiol
      implanted ovariectomized ewe treated with caffeine.
AB  - Caffeine, a trimethylxanthine alkaloid, is a psycho-active drug that effects a
      wide range of physiological systems, including the reproductive system. Reports
      of infants with intra-uterine growth retardation and lowered birth weight as a
      result of in utero exposure to caffeine, are increasing. The drug is also known
      to alter steroidogenesis but it is not certain whether this is a direct and/or an
      indirect effect with the involvement of the central nervous system. Thus, an
      experiment was designed to determine the effect of acute caffeine administration
      on the circulating concentrations of gonadotrophins and prolactin in the
      ovariectomized oestradiol-implanted ewe. A single intravenous dose of caffeine
      (20 mg kg-1 bodyweight) did not affect circulating gonadotrophin concentrations
      with the parameters for the pulsatile secretion of luteinizing hormone (LH) and
      the mean concentration of follicle stimulating hormone (FSH) being similar in
      both experimental and control groups. Circulating prolactin levels, on the other
      hand, were significantly (P < 0.01) elevated following intravenous treatment with
      caffeine. The effect was immediate following caffeine administration with
      elevated concentrations being maintained over the next 3 h before their return to
      pre-treatment concentrations. The response was bi-phasic with peaks of prolactin
      concentrations at 1 and 3 h. The results of this experiment show that acute
      caffeine exposure does not affect the secretion of gonadotrophins from the
      anterior pituitary gland. Furthermore, they show that acute administration of
      caffeine stimulates prolactin secretion via an action that is independent of
      oestradiol feedback and which we suggest, may involve the ACTH/adrenal axis.

PMID- 9231239
TI  - Ovulation rate and the concentrations of LH, FSH, GH, prolactin and insulin in
      ewes infused with tryptophan, tyrosine or tyrosine plus phenylalanine during the
      luteal phase of the oestrous cycle.
AB  - Dietary amino acid precursors for cathecholamineric and serotonergic
      neurotransmitters may be important in the mechanism of nutritional effects on
      ovulation rate. This paper reports the results of three experiments that examined
      the effect of such amino acids on ovulation rate and the concentrations of FSH
      and LH in sheep. In three separate experiments, groups of ewes were infused, over
      Days 9 to 13 of the oestrous cycle, with either tryptophan (n = 11), tyrosine (n
      = 11) or a mixture of tyrosine and phenylalanine (n = 11). Control ewes (n = 12
      in each experiment) were infused with a vehicle over the same period. None of the
      amino acids infused effected ovulation rate or plasma concentrations of LH, FSH,
      GH or prolactin. The infusion of a mixture of tyrosine and phenylalanine
      increased insulin concentrations. The infusion of these amino acids was not
      associated with changes in gonadotrophin concentrations and therefore the effect
      of nutrition on ovulation rate in ewes does not seem to involve an increase in
      the availability of tryptophan, tyrosine or phenylalanine. Increasing the uptake
      of other amino acids that compete with tryptophan, tyrosine or phenylalanine for
      the large neutral amino acid transporter may cause a decrease in the availability
      of tryptophan, tyrosine or phenylalanine thereby eliciting the effects of
      nutrition on ovulation rate. However, this hypothesis remains to be tested.

PMID- 9231240
TI  - Assessment of the acrosomal status of membrane-intact ram spermatozoa after
      freezing and thawing, by simultaneous lectin/Hoechst 33258 staining.
AB  - We have evaluated the effect of freezing and thawing on the acrosomal status of
      ram spermatozoa, especially those that withstood cryopreservation as assessed by
      membrane integrity. To this end, we performed simultaneous lectin/Hoechst 33258
      staining, and compared the ability of three fluoresceinated lectins. Ram
      spermatozoa were treated with fluorescein isothiocyanate-labelled Pisum sativum
      lectin (PSA), fluorescein isothiocyanate-labelled Arachis hypogea lectin (PNA)
      and fluorescein isothiocyanate-labelled Triticum vulgaris lectin (WGA) and
      simultaneously with Hoechst 33258 for determination of membrane integrity and
      acrosomal status. In all cases, three forms were readily distinguished by their
      distribution pattern. For both PSA and PNA, the most abundant form found in fresh
      semen consisted of fluorescence on the acrosomal area. This form corresponds to
      acrosome-intact spermatozoa, as assessed by Differential Interference Contrast
      (DIC) microscopy. Two minor forms showed weak fluorescence on the equatorial
      segment or no fluorescence on the head. DIC microscopy revealed that both forms
      were associated with acrosome-lost spermatozoa. WGA labelling showed two forms,
      one of which consisted of fluorescence on the entire head, albeit more intensely
      on its anterior segment. Spermatozoa in this form were acrosome-intact by DIC.
      The other form lacked fluorescence on the acrosomal region, but still showed
      faint fluorescence in the posterior region. This form was acrosome-lost by DIC.
      Incubation of fresh spermatozoa with calcium ionophore A23187 for up to 1 h
      significantly increased the percentage of those forms identified as acrosome
      reacted as described above. This was confirmed by the time-dependent accumulation
      of these forms, as well as by DIC microscopy. At all times, differences among
      values obtained using these three lectins were not significant. Freezing and
      thawing led to a decrease of both membrane integrity and acrosomal integrity,
      irrespective of the lectin used. However, almost all spermatozoa that withstood
      cryopreservation, as evaluated by Hoechst exclusion, showed intact acrosomes. In
      this case, no differences between fresh and frozen/thawed samples were observed.
      These results suggest that the structural integrity of ram spermatozoa is mostly
      unaffected after cryopreservation, suggesting that it is damage to the plasma
      membrane that is primarily responsible for the low fertility of cryopreserved
      samples.

PMID- 9231241
TI  - Effect of experimental infection with Listeria monocytogenes on the development
      of pregnancy and on concentrations of progesterone, oestrone sulphate and 15
      ketodihydro-PGF2 alpha in the goat.
AB  - The effect of Listeria monocytogenes infection on hormone levels in pregnant
      goats was studied. Four goats (Group I) received an intravenous inoculation of a
      bacterial culture (Type 1) on Days 69-77 and another four goats (Group II)
      received a similar inoculation on Days 105-106 of gestation. Five non-inoculated
      goats were used as controls. Plasma was analysed for progesterone, oestrone
      sulphate and 15-ketodihydro-PGF2 alpha. The status of the foetus was followed
      using real-time ultrasonography. Three of the four goats in Group I aborted 8-10
      days after inoculation. The fourth goat gave birth to a normal live kid at term.
      The three goats which aborted showed clinical signs of disease in connection with
      abortion. In Group II, all goats aborted after 9-11 days. All the goats showed
      clinical symptoms of disease from a few days after inoculation and the symptoms
      continued until abortion. The clinical symptoms of disease were more pronounced
      in Group II than in Group I. L. monocytogenes was isolated from all aborted
      foetuses. None of the control goats aborted. Ultrasound examination revealed
      foetal death either immediately before or up to 2 days before abortion.
      Mummification had begun in the foetus that had been dead for 2 days before
      expulsion. In comparison with pre-inoculation plasma levels in Group I, a
      significant decrease (P < 0.05) in progesterone levels and an increase in 15
      ketodihydro-PGF2 alpha levels were observed from Days 4 and 6 after inoculation,
      respectively. In Group II, a significant decrease (P < 0.05) in progesterone
      levels and an increase in 15-ketodihydro-PGF2 alpha levels in plasma were
      observed from Days 8 and 6, respectively. The oestrone sulphate levels decreased
      slightly in the inoculated goats a few days before abortion. The pattern of
      changes in levels around abortion was similar to the pattern present in the
      control animals around parturition. However, oestrone sulphate levels did not
      increase in the inoculated groups before abortion in contrast to goats which
      delivered healthy kids. The changes in levels of 15-ketodihydro-PGF2 alpha in
      goats that aborted indicated that the endocrine foetal-placental function was
      disturbed, which was most likely due to the establishment and development of L.
      monocytogenes in the placenta and foetus.

PMID- 9231242
TI  - Superovulation in cattle: effect of FSH type and method of administration on
      follicular growth, ovulatory response and endocrine patterns.
AB  - Although different FSH preparations and injection regimens are used to
      superovulate cattle, the optimum treatment regimen and blood concentrations of
      FSH to induce effective superovulatory responses are currently not known. The
      current objective was to evaluate the pattern of follicular growth, oestradiol-17
      beta(E2) concentrations and yield of embryos in heifers following superovulation
      with two different pFSH preparations reportedly differing in LH content. In
      experiment 1, 90 synchronised heifers were superovulated at mid-cycle using a 2 x
      2 factorial design comparing Folltropin (Vetrepharm; low LH) with Pluset
      (Serovet; FSH:LH ratio 1:1) administered either as a single or multiple (8 for
      Folltropin, MF and 10 for Pluset, MP) injections. Animals were inseminated during
      oestrus which was induced with prostaglandin F2 alpha analogue and embryos were
      recovered 7 days later. Overall, Pluset treatments compared with Folltropin
      resulted in more ovulations and unfertilized or degenerate embryos (P < 0.05).
      Multiple injections resulted in more (P < 0.05) freezable (MF = 55 +/- 1.2; MP =
      3.8 +/- 1.0) and transferable embryos (MF = 2.68 +/- 0.9; MP = 2.71 +/- 0.9) than
      single injections (SF = 2.2 +/- 0.5 and 1.0 +/- 0.3 respectively; SP = 2.6 +/-
      0.8 and 1.3 +/- 0.4 respectively); there was also a higher (P < 0.05) percentage
      embryo recovery rate. In two subsequent experiments, animals (n = 17) were
      superovulated with either single or multiple injections of Folltropin or Pluset
      as described and blood samples were collected and analysed for E2 concentrations.
      Ovarian scanning was carried out until 72 h after the first FSH injection, to
      count medium (5-9 mm) and large (> or = 10 mm) follicles. Heifers treated with SP
      had higher E2 concentrations in comparison with heifers treated with SF at 18, 36
      48 and 84-96 h after the FSH injection. There were no differences in E2
      concentrations in heifers treated with MF or MP treatments. Heifers treated with
      SP had greater numbers of follicles compared to SF treated heifers (21.0 +/- 3.1
      vs 13.9 +/- 2.2; P = 0.089) on the third day after FSH injection. There were no
      differences between the numbers of medium and large follicles in heifers treated
      with MF or MP at any time throughout the experimental period. These data indicate
      that a single injection of Folltropin or Pluset can result in multiple ovulations
      and that the E2 profiles are different following single injections of either
      Folltropin or Pluset.

PMID- 9231243
TI  - Continuous infusion of relaxin on periparturient progesterone, oxytocin and
      relaxin plasma concentrations and time of parturition in beef heifers.
AB  - These studies were designed to determine whether continuous i.v. infusion of
      increasing dosages of porcine relaxin during late pregnancy in beef heifers would
      influence circulating blood concentrations of relaxin, progesterone and oxytocin,
      and time of onset of parturition. Beef heifers were bred by artificial
      insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone
      infusion and blood sampling from Day 277 to Day 286. Intravenous infusion of
      purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at
      increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280,
      500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283-286).
      Phosphate-buffered saline (PBS, 10 ml h-1) was infused during these same times to
      control animals (n = 6). Relaxin treatment steadily increased the circulating
      plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared
      with less than 0.5 ng ml-1 in PBS-treated controls. Relaxin infusion in
      increasing dosages over the treatment time was associated with a significant
      decrease (P < 0.01) in plasma progesterone concentration compared with the PBS
      controls. The rate of change in progesterone levels between pRLX and PBS groups
      differed (P < 0.05) at 300 U h-1, 600 U h-1 and 700 Uh-1 dosage intervals,
      respectively. Plasma levels of oxytocin at 4 h intervals remained similar (P >
      0.05) during the pretreatment period and throughout continuous infusion of pRLX
      and PBS. Mean concentrations of oxytocin in PBS control heifers peaked at 0.95
      pgml-1 during the corresponding infusion of 700 Uh-1 pRLX, which peaked at 0.77
      pgml-1. Although continuous i.v. infusion of relaxin resulted in a decrease in
      circulating blood levels of progesterone, it did not significantly reduce the
      interval between the beginning of pRLX treatment and parturition compared with
      the PBS-infused control heifers. These results indicate that continuous i.v.
      infusion of high levels of porcine relaxin resulted in a decrease in progesterone
      secretion in late pregnant beef heifers.

PMID- 9231244
TI  - Efficiency of the OVATEC unit for estrus detection and calf sex control in beef
      cows.
AB  - Seventy five spring calving Gelbvieh and Angus cows were utilized over a three
      year period to evaluate the usefulness of the OVATEC intravaginal probe for
      indicating the onset of estrus and providing the possibility to influence the sex
      of the offspring by choosing a breeding time in relation to critical changes in
      cervical mucus conductivity. Cows were randomly assigned by breed each year into
      one of four treatments: (1) probed and inseminated when impedance values
      declined, creating conditions expected to favor X-bearing sperm and with it an
      increase in the conception of females (PF); (2) probed and inseminated when
      impedance values were rebounding, expected to favor Y-bearing sperms and with it
      an increase in the conception of males (PB); (3) standing estrus (AI); or (4)
      natural service by bull (NS). Cows grazed or were fed hay from tall fescue-legume
      pastures. Lutalyse was used to synchronize estrus in a two injection scheme.
      Vaginal probe readings were taken at first injection, second injection and every
      12 h thereafter for 6 days. Visual observations for estrus were obtained for PF,
      PB and AI every 12 h postsecond injection. Rectal palpations of ovaries were
      obtained at standing heat in all but NS treatments. In cycling cows, probe
      readings increased prediction of estrus onset (P < 0.10) compared to visual
      observations and were similar (P > 0.95) to rectal palpations in all probed cows.
      PF cows delivered heifer calves at greater rates (P < 0.025) than all other
      treatments whereas PB cows delivered bulls at greater rates (P < 0.05) than all
      other treatments. Heifer to bull ratios were not different (P > 0.95) for AI or
      NS treatments. The results of this study indicate that the potential exists for
      increasing female offspring conceptions utilizing cervical mucus conductivity as
      a gauge for insemination times.

PMID- 9231245
TI  - Fertility of sperm from a tetraparental chimeric bull.
AB  - The purpose of the present study was to examine the ability of a tetraparental
      Chimera in producing IVF embryos. Cumulus oocytes complexes (COCs) were matured
      in vitro for 22 h. Frozen-thawed sperm of a Chimera (CH), as well as Japanese
      Black (JB), Limousin (L), Japanese Brown (JBr), Holstein (H) bulls were used for
      IVF. The chromosome preparations were made from peripheral lymphocytes. Based on
      chromosome analysis the Chimera had apparently normal chromosomes (29 acrocentric
      pairs, one large sub metacentric X chromosome and one small sub metacentric Y
      chromosome). The proportion of acrosome reacted spermatozoa after 1 h incubation
      was higher (P < 0.01) with the Chimera (CH) than with the Holstein and in
      Japanese Brown bulls, but did not differ from Japanese Black and Limousin bull
      sperm (79.0%, 71.2%, 72.5%, 57.8% and 57.0% for CH, JB, L, JBr and H sperm,
      respectively). Fertilization rates observed after 5 h of sperm-oocyte incubation
      with Chimera (O-CH) sperm were higher (P < 0.05) than with Japanese Brown (O-JBr)
      and (P < 0.01) than with Holstein (O-H) sperm, but did not differ from Japanese
      Black (O-JB) and Limousin (O-L) sperm (36/44, 81.8%; 28/35, 80.0%; 25/36, 69.4%;
      19/43, 44.2% and 6/33, 18.2% for O-CH, O-JB, O-L, O-JBr and O-H, respectively).
      The cleavage rates of IVM oocytes inseminated with Chimera sperm were also higher
      (P < 0.001) than in Holstein, (P < 0.01) Japanese Brown and (P < 0.05) Limousin,
      but did not differ from Japanese Black sperm (181/239, 75.7%; 123/171, 71.9%;
      108/186, 58.1%; 80/196, 40.8% and 30/186, 16.1% for O-CH, O-JB, O-L, O-JBr and O
      H, respectively). The blastocyst rates of IVM oocytes inseminated with sperm were
      higher (P < 0.05) than in Limousin, Japanese Brown and Holstein, but did not
      differ from Japanese Black (69/181, 38.1%; 48/123, 39.0%; 27/108, 25.0%; 7/30,
      23.3% and 16/80, 17.8% for O-CH, O-JB, O-L, O-JBr and O-H, respectively). Three
      findings suggested the sperm from this tetraparental Chimeric bull were able to
      be used for producing bovine IVF embryos.

PMID- 9231246
TI  - The effect of sperm preparation on the timing of penetration in bovine in vitro
      fertilization.
AB  - Five hundred and seventy three follicular bovine cumulus oocyte complexes were
      matured in vitro and in vitro fertilization (IVF) carried out with the native
      semen of a brown bull. Half the cultures were fertilized with transmigrated
      spermatozoa (TM), the other with sperm suspensions prepared using the swim-up
      (SU) process. Five, six and seven h after IVF the oocytes were fixed and stained.
      Using a phase-contrast microscope, both the incidence of penetration and
      polypenetration and the stage of development of a pronucleus were determined.
      With the TM samples, five hours after IVF penetration was observed in 39.3 per
      cent of the oocytes, whereas with the SU samples the first instances of
      penetration were observed only two hours later (4.2%). By this time a normal
      looking pronucleus was observed in 16.4 per cent of the oocytes in the TM group.
      Polypenetration was seen only after seven hours of incubation. This study showed
      that TM spermatozoa penetrate the oocyte earlier than SU spermatozoa.

PMID- 9231247
TI  - Influence of an antiprogestin (onapristone) on in vivo and in vitro
      fertilization.
AB  - The effects of a progesterone antagonist (onapristone) on heat synchronization,
      luteinizing hormone (LH) surge, ovulation, oocyte maturation and fertilization of
      superovulated ewes were studied. Its effects on in vitro bovine oocyte maturation
      and fertilization were also studied. Estrus synchronization and superovulation
      treatments were applied to 39 adult ewes using an intravaginal sponge with
      fluorgestone acetate for 9 days with injections of prostaglandin F2 alpha and
      pregnant mare's serum gonadotrophin given 24 h before sponge withdrawal. The
      animals were randomly assigned to four different groups; T1 receiving only the
      synchrony treatment (n = 11); T2 ewes received two injections of onapristone (1
      mg kg-1, i.v.) 12 h apart from 3 h after sponge withdrawal (n = 10); T3 ewes
      received two injections of progesterone 12 h apart from sponge withdrawal (n =
      10); and, T4 ewes received both onapristone and progesterone as described (n =
      8). Ewes were mated by a fertile male during estrus. Progesterone and LH were
      measured during the superovulation period in plasma samples taken every 4 h.
      Uterine flushings for ova recovery were performed at 5 days (n = 25), 48 h (n =
      5) and 24 h (n = 5). Non-fertilized oocytes collected at 24 and 48 h were checked
      for meiosis resumption. The effects of two doses of onapristone (D1 and D2) on in
      vitro bovine oocyte maturation (control = 100, D1 = 100 and D2 = 100) and
      fertilization (control = 107, D1 = 40 and D2 = 75) were also studied. The
      percentage of animals showing heat signs was significantly lower in group T3 (50%
      vs. 100%). The onset of oestrus (27.6, 24.8, 68.8 and 25.5 h, respectively for
      T1, T2, T3 and T4) and an LH surge (32.3, 28.8, 76.5 and 30.5 h, respectively for
      T1, T2, T3 and T4) after sponge withdrawal were significantly delayed in group
      T3. There were no significant differences in the intervals between estrus and LH
      surge among groups (4.61 +/- 0.75 h). The response and ovulation rates until 40 h
      after sponge withdrawal (group T3 excluded) were similar among groups, but the
      fertilization rates were significantly lower in groups T2 and T4 when compared
      with T1 (2% and 3% vs. 41%, respectively; P < 0.001) due to sperm arrest in the
      cervix. Ova recovery rate decreased significantly from 24-48 h to 5 days and was
      not affected by treatments (76.9% vs. 37.1% respectively). Onapristone did not
      affect the resumption of meiosis. Fertilization of bovine oocytes in vitro
      decreased significantly only in group D2 when compared to control (48% vs. 62.6%,
      respectively). In conclusion, onapristone treatment during the preovulatory
      period did not interfere with normal synchronization of estrus, ovulation and
      oocyte maturation but severely compromised fertilization by arresting spermatozoa
      in the cervix.

PMID- 9231248
TI  - Effect of progesterone pre-treatment on steroid secretion rates and follicular
      fluid insulin-like growth factor-1 concentrations in seasonally anoestrous ewes
      treated with gonadotrophin releasing hormone.
AB  - Progesterone priming is known to prevent premature luteal regression in
      seasonally anoestrous ewes induced to ovulate with small dose multiple injections
      of gonadotrophin releasing hormone (GnRH), but the precise mechanisms involved
      are poorly understood. The main objective of the present study was to investigate
      the effect of progesterone priming, before and after a period of treatment with
      GnRH, on the biochemical activity of ovarian follicles collected from seasonally
      anoestrous ewes. Ewes in Groups 1 and 2 (6 ewes/group) received progesterone
      priming or vehicle alone, respectively, and were slaughtered 72 h later. Ewes in
      Groups 3 and 4 (6 ewes/group) were similarly primed with progesterone or vehicle
      only, respectively, and then 72 h later received 2-hourly injections of 250 ng
      GnRH for 20 h, followed 2 h later by a single bolus injection of 300 micrograms
      GnRH. They were then slaughtered 2 h after the bolus injection. All normal
      growing follicles > or = 2.0 mm diameter were dissected from the ovaries of all
      ewes and after measurement of their diameter, were incubated in Eagle's Basal
      Medium for 2 h to measure their steroid secretion rates. The fluid from each
      follicle was then aspirated and assayed for total insulin-like growth factor-1
      (IGF-1) content. The luteinizing hormone receptor content of the whole follicle
      was estimated using 125I-labelled human chorionic gonadotropin (hCG). The
      follicles were classified as either non-oestrogenic or oestrogenic if their
      oestrogen production rate was < or = 300 or > 300 pg/ml/2h, respectively. The
      mean diameter of oestrogenic follicles (5.72 +/- 0.25 mm) was significantly (P <
      0.001) larger than that of non-oestrogenic ones (3.93 +/- 0.25 mm). The mean
      numbers of oestrogenic and non-oestrogenic follicles were not significantly
      different among the four treatment groups. Oestradiol production rate was
      significantly (P < 0.001) increased as a result of GnRH treatment, but only in
      large oestrogenic follicles. Testosterone production rate was, however,
      significantly (P < 0.05) increased by both GnRH and progesterone in both classes
      of follicle. While GnRH treatment tended to decrease IGF-1 concentrations in
      small non-oestrogenic follicles, it significantly (P < 0.05) increased
      concentrations in large oestrogenic ones. IGF-1 concentrations were, however,
      significantly (P < 0.05) increased in both classes of follicle collected from
      progesterone-primed ewes treated with GnRH. Regardless of treatment, follicular
      fluid IGF-1 concentrations were significantly (P < 0.001) higher in small non
      oestrogenic follicles compared to large oestrogenic ones. An increase in 125I-hCG
      binding to large oestrogenic follicles was observed in response to progesterone
      (P-0.07) in GnRH treated ewes. These results indicate differences in the
      biochemical activity of follicles attributable to progesterone priming which may
      be casually related to defective luteal function after ovulation.

PMID- 9231249
TI  - Effect of the rate of progesterone decline at luteolysis on the ovulatory
      follicles and subsequent estrous cycle length in ewes.
AB  - Follicular and interestrous characteristics were examined in 34 ewes after
      experiencing either a rapid decline in plasma concentrations of progesterone at
      luteolysis [prostaglandin F2 alpha (PGF2 alpha)-induced] or a slow rate of
      decline, lasting over 72 h. All ewes were given PGF2 alpha on day 10 (day 0 =
      estrus). A slow rate of decline was established in 17 ewes by the intravenous
      infusion of progesterone initially at 72 ml h-1, delivering 4.5 mg progesterone h
      1, then decreasing the infusion rate by 1 ml h-1 for the next three days.
      Seventeen additional ewes, predestined to experience a rapid decline in
      progesterone, were infused with vehicle. In Experiment 1, after infusion, ewes (6
      ewes/group) were necropsied at the onset of estrus and follicle diameter was
      determined, follicular fluid was aspirated and the remaining follicular wall was
      microscopically examined to determine the number of granulosa cell layers. In
      Experiment 2, the interestrous interval, after infusion, was observed in both
      groups of ewes (11 ewes/group). Ewes experiencing a rapid rate of progesterone
      decline at luteolysis had no differences in follicle diameter nor follicular
      concentration of progesterone or estradiol but their ovulatory follicles
      contained fewer (P < 0.01) granulosa cell layers and the resulting estrous cycle
      was longer (P < 0.05) than ewes experiencing a slow rate of progesterone decline.

PMID- 9231251
TI  - The arena test and cortisol response of sheep as indirect selection criteria for
      the improvement of lamb survival.
AB  - As part of a study of possible indirect selection criteria for the genetic
      improvement of lamb survival in the Australian Merino, two experiments were
      conducted. These experiments involved ewes from two flocks, one selected for
      superior lamb survival (Fertility Flock) the other an unselected flock (Random
      Flock). In the first experiment, the behaviour in an arena test of ewes from the
      two flocks was measured under two conditions; the ewes were tested either singly
      or in a group of four and the ewes were tested when in oestrus or not. When the
      ewes were tested singly, differences were detected between the two flocks in the
      total distance travelled, the minimum distance from a human operator in the arena
      and in the number of bleats. When the ewes were tested in a group of four, the
      differences in distance travelled and number of bleats disappeared; the
      difference in closest approach was maintained but the order of the two flocks was
      reversed; a difference appeared in the furthest distance from the operator. The
      experiment also showed that arena behaviour was not affected by the oestrous
      state of the ewes. In the second experiment, the cortisol response of the adrenal
      gland to stimulation by ACTH or by an external influence (barking dog) was
      examined in ewes from the two flocks. There were no differences between the two
      flocks in cortisol response to any of the stimuli. The results show that the
      behaviour of sheep in the two types of test is different, that the single-animal
      test may be the more appropriate when improvement in lamb survival is the
      objective and that the response of the adrenal gland shows little promise as an
      indirect criterion for selection.

PMID- 9231250
TI  - Simultaneous detection of the acrosomal status and viability of incubated ram
      spermatozoa using fluorescent markers.
AB  - Incubation of diluted ram spermatozoa at 39 degrees C results in a high
      percentage of acrosome reactions, but previously we have not been able to
      demonstrate the viability of these cells. Detection of the viability and stages
      of acrosomal exocytosis, either spontaneous or induced, was carried out using
      fluorescent probes. Propidium iodide (PI) was used to determine cell viability
      and, simultaneously, FITC-Pisum sativum lectin (FITC-PSA) was used to assess
      acrosomal status by staining glycoproteins in the acrosome of permeabilised
      spermatozoa. Diluted ram semen was incubated for 6 hours at 39 degrees C. At 2
      hourly intervals, samples were taken and examined for evidence of a spontaneous
      acrosome reaction. In addition, calcium ionophore A23187 was used to induce the
      acrosome reaction and samples were examined at 10 minute intervals. PI was added
      and then washed out by filtration. Smears were made and air-dried, permeabilised
      with absolute ethanol and then stained with FITC-PSA. The slides were later
      viewed under the fluorescence microscope with a peak excitation wavelength of 488
      nm. With this combination of two fluorescent probes using a single excitation
      wavelength, both the cell viability and the acrosomal status could be
      simultaneously and easily visualized. Results showed four categories of staining:
      PI-ve/PSA + ve (Live and acrosome-intact), PI + ve/PSA + ve (dead and acrosome
      intact), PI - ve/PSA - ve (live and acrosome-reacted) and PI + ve/PSA - ve (dead
      and acrosome-degenerated). About 75% spermatozoa that were acrosome-reacted were
      still viable after 4 h incubation in the absence of ionophore, and approximately
      90% spermatozoa were acrosome-reacted and still viable after 30 min incubation in
      the presence of ionophore.

PMID- 9231252
TI  - Induction of hydrometra in goats by means of active immunization against
      prostaglandin F2 alpha.
AB  - Hydrometra is a pathological condition of the uterus which is characterized by
      accumulation of aseptic fluid in the presence of a persistent corpus luteum. It
      forms a major cause of subfertility in goats. Active immunization against
      prostaglandin F2 alpha (PGF2 alpha), the luteolytic hormone in this species, was
      used to explore the possibility for artificial induction of this pseudopregnant
      condition. During the breeding season, 11 goats (group I) were immunized with 5
      mg PGF2 alpha-ovalbumin conjugate in Freund's complete adjuvant, 4 goats were
      control-immunized (group CI) and 5 goats remained untreated (group C). Jugular
      blood samples were taken twice a week (monday and thursday) for measurements of
      plasma progesterone and binding of 3HPGF2 alpha. In conjunction with blood
      sampling, transcutaneous ultrasonographic examination of the uterus took place to
      detect the presence of fluid in the uterus. Before and immediately after
      immunization, the mean (+/-SD) duration of luteal phases (progesterone
      concentrations > or = 1 ng ml-1) was 16.7 +/- 1.6 (n = 39), 17.8 +/- 1.3 (n = 23)
      and 16.9 +/- 1.1 (n = 18) days in animals of group I, CI and C respectively. Ten
      goats of group I developed an antibody titre. Persistence of luteal function
      (mean duration +/-SD: 150.3 +/- 23.5 days) occurred in 6 of these animals and in
      1 goat of group CI. Accumulation of fluid in the uterus in group I was first
      observed between day 31 and 38 of the prolonged luteal phase. Discharge of
      uterine fluid occurred as soon as the plasma progesterone concentration reached a
      level lower than 0.5 ng ml-1. It is concluded that immunization against PGF2
      alpha is an effective method to induce pseudopregnancy in goats, providing a
      model for studies on luteal maintenance and uterine function in the absence of a
      conceptus.

PMID- 9231253
TI  - Lack of effects of growth hormone administration on ovarian function of lactating
      goats.
AB  - Exogenous growth hormone (GH, 5 mg d-1) was given daily to lactating goats for 4
      weeks (Experiment 1) and 100 days (Experiment 2). Treatment effects on milk
      production and milk composition were assessed. At the end of treatment, goats
      were slaughtered and one ovary was processed for histological analysis while the
      largest follicles of the other ovary were dissected, measured and incubated in
      vitro (Experiment 1). In Experiment 2, following a synchronisation treatment, a
      superovulatory regime of pregnant mare's serum gonadotrophin (eCG) was given and
      ovulation rate measured at laparoscopy. In both experiments, GH administration
      raised milk yield (28.6% and 17% in Experiments 1 and 2 respectively).
      Circulating IGF1 concentrations were also increased following treatment. In
      contrast, no treatment effects were detected on the ovaries. In Experiment 1, the
      total population of antral follicles, their atresia, the number in specific size
      classes and the size of the largest healthy or atretic follicles were similar in
      control and GH treated ovaries. In addition, steroidogenesis (oestradiol and
      testosterone) by large follicles was also unaffected by treatment. In Experiment
      2, eCG induced ovulation rate (control 6.9 +/- 7.6, treated 4.2 +/- 2.8) was also
      similar between groups. It is concluded that GH administration to lactating
      goats, while increasing milk production has no detrimental or positive
      consequences on ovarian function.

PMID- 9231254
TI  - Oestrus, ovulation and peri-ovulatory hormone profiles in tethered and loose
      housed sows.
AB  - Multiparous sows that had been tethered during lactation were put in two
      different housing conditions after weaning (Day 0); the sows were either tethered
      by neck chain, or individually housed in a pen of approximately 6 m2. After two
      months, ten tethered and eleven loose housed sows were used to assess stress and
      reproductive parameters. Stereotypic behaviour after the afternoon feeding was
      assessed from Day 18 onwards; at Day 53 stereotypic behaviour tended to occur
      during a higher percentage of time in the tethered sows (P = 0.11) and at Day 66,
      the differences were significant (tethered, 78 +/- 5 vs. loose-housed, 40 +/- 10%
      of time (mean +/- sem); P = 0.03). At Day 35 and 55, cortisol profiles after
      afternoon feeding were similar for the two groups of sows (P > 0.10). Around
      oestrus (approximately Day 64), the profiles of oestradiol-17 beta, luteinizing
      hormone and progesterone were measured and proved to be similar for both
      treatment groups (P > 0.10). The duration of oestrus was shorter in the tethered
      sows (42 +/- 4 vs. 63 +/- 2 h; P < 0.001) and, consequently, the timing of
      ovulation during oestrus (h after onset of oestrus) was advanced in the tethered
      sows (28 +/- 2 vs. 41 +/- 2; P < 0.001). The duration of ovulation did not differ
      (tethered, 2.9 +/- 0.5 vs. loose-housed, 2.1 +/- 0.2 h; P = 0.16). The sows were
      sacrificed at Day 5 after ovulation; ovulation rate, fertilization rate, embryo
      development and embryo diversity were similar for the two groups, as were adrenal
      weight and size of adrenal cortex. Duration of oestrus and the levels of
      stereotypies at Day 60 tended to be negatively related in the tethered sows (P =
      0.07), but not in the loose-housed sows (P = 0.65). In conclusion, sows that had
      been tethered during pregnancy and lactation, and were housed loose or were
      tethered again at weaning within two months differed both in stereotypic
      behaviour and in duration of oestrus, without apparent effects on reproductive
      hormones.

PMID- 9231256
TI  - The effects of contact frequency and transport on the efficacy of the boar
      effect.
AB  - Ninety six Large White/Landrace cross-bred gilts were used in this study, sixteen
      gilts being allocated to each of six treatments. The treatments compared the
      effects on puberty attainment of exposing gilts to boar contact either 0, 1 or 3
      times daily (C, D and 3D), with or without the addition of transport "stress"
      (T). Treatments began at a mean gilt age of 160 days and continued for 40 days.
      The duration of each period of boar contact was 20 min. Those gilts receiving
      transport "stress" were placed on a trailer daily for the first ten days of the
      study and driven at a constant speed for 20 min. There was no significant effect
      of transport alone on the timing of gilt puberty attainment. Boar exposure
      significantly increased the proportion of gilts attaining puberty within 40 days
      of the commencement of treatments (P < 0.05) compared with gilts not receiving
      boar contact. Boar exposure three times daily significantly reduced mean gilt age
      at puberty relative to no boar exposure (190.2 vs. 202.3 days of age
      respectively, P < 0.01) while once-daily boar exposure gave an intermediate value
      (196.7 days). In addition, a significant (P < 0.01) interaction occurred between
      boar contact frequency and transport in this study. It is concluded that (a)
      transport alone does not provide a significant stimulus for early puberty
      attainment in the gilt, (b) the pubertal response of the gilt to the boar effect
      is enhanced when boar contact occurs several times each day compared with a
      single boar contact period, and (c) a combination of frequent boar contact and
      transport may result in a greater degree of gilt puberty stimulation than
      frequent boar contact alone.

PMID- 9231255
TI  - Relaxin and estrogen synergistically accelerate growth and development in the
      uterine cervix of prepubertal pigs.
AB  - This study was designed to determine the development and growth-promoting effects
      of relaxin with or without estrogen on the uterine cervix of prepubertal gilts.
      Twenty littermate gilts of similar body weight (33 +/- 3 kg; mean +/- SE) at 80
      days of age were randomly assigned to four treatments: Vehicle (CONTROL, 1 ml PBS
      and 1 ml vegetable oil, n = 5); Relaxin (Relaxin, in PBS, 1 ml, 167 micrograms ml
      1, n = 5); Estradiol Benzoate (EB, in vegetable oil, 1 ml, 2 mg ml-1, n = 5); and
      Relaxin plus EB (Relaxin + EB, at the same doses, n = 5), total six intramuscular
      injections for all treatments. Twenty four hours after the last injection,
      hysterectomy was performed, and the uterine tissues were immediately frozen at 
      80 degrees C. Samples were taken from the middle portions of the cervix and the
      uterine horns and dried to a constant weight to determine the dry weight and
      water concentration. Homogenates of uterine horns and cervices were analyzed for
      concentrations and contents of protein, hydroxyproline (collagen index) and DNA.
      Relaxin alone had no significant effect on any parameters (i.e., wet weight,
      Relaxin vs. CONTROL: 36 +/- 5 vs. 28 +/- 3 g uterus-1, dry weight 5.6 +/- 0.6 vs.
      4.4 +/- 0.4 g uterus-1). EB alone increased significantly (P < 0.05) wet weight
      of the uterus (EB vs. CONTROL: 85 +/- 23 vs. 28 +/- 3 g uterus-1), dry weight (EB
      vs. CONTROL: 14.5 +/- 3 vs. 4.4 +/- 0.4 g uterus-1), and hydroxyproline content
      (EB vs. CONTROL: 47.2 +/- 13 vs. 12.6 +/- 4 mg cervix-1). In the presence of EB,
      relaxin treatment increased all measurements compared with CONTROL (i.e., wet
      weight, Relaxin + EB vs. EB: 136 +/- 34 vs. 28 +/- 3 g uterus-1). Compared with
      EB, Relaxin + EB significantly (P < 0.05) increased the uterine wet weight
      (Relaxin + EB vs. EB: 136 +/- 34 vs. 85 +/- 23 g uterus-1), the hydroxyproline
      content (Relaxin + EB vs. EB: 91 +/- 29 vs. 47 +/- 13 mg cervix-1), and DNA
      content (Relaxin + EB vs. EB: 8.1 +/- 2 vs. 5.4 +/- 1 mg cervix-1). These results
      indicate that the growth-promoting effects of relaxin on the uterus and cervix
      may be, at least partly, estrogen-dependent and that the growth and development
      of the uterus and cervix can be accelerated by a combination of relaxin and
      estrogen treatment.

PMID- 9231258
TI  - A comparison of dissected follicle numbers and follicle counts on the ovarian
      surface for the evaluation of ovarian follicular populations in Bos indicus cows.
AB  - Ovaries (n = 140) from 70 mixed-age multiparous, lactating Brahman cross (3/4 -
      7/8 Bos indicus) cows were used to examine the hypothesis that counts of
      follicles visible on the surface of the ovaries of Bos indicus cows and their
      classification into diameter size classes, are closely correlated with numbers of
      follicles in those size classes found by complete dissection of the ovary.
      Immediately after ovariectomy, mean diameters (long and short axes averaged) of
      all follicles > or = 2 mm visible on the surface of each ovary were measured. All
      follicles > or = 2 mm were dissected from the ovaries, excess stroma removed and
      follicle diameters measured under a stereomicroscope using an ocular graticule.
      For each ovary, follicles were classified in either small (< 4 mm), medium (4-8
      mm) or large (> 8 mm) categories based on either diameters of surface or
      dissected follicles. Data for numbers of surface and dissected follicles (mean +/
      SE) in small, medium, large categories and total follicle numbers, respectively,
      were 24.4 +/- 1.6 vs. 28.0 +/- 1.9, 1.6 +/- +0.2 vs. 11.6 +/- 1.0, 0.5 +/- 0.1
      vs. 0.7 +/- 0.1 and 26.4 +/- 1.6 vs. 40.4 +/- 2.5. Correlation coefficients (r)
      for counts of surface and dissected follicles in small, medium, large and total
      follicle numbers were 0.76, 0.40, 0.69 and 0.79, respectively. Medium size
      follicles presented only a small translucent area on the surface of the ovary,
      leading to an underestimate of numbers when categorised by surface evaluation.
      Counts of follicles visible on the surface of the ovaries of Bos indicus cows and
      their classification into size classes based on estimated diameter, are closely
      correlated with numbers of follicles in those size classes found at dissection of
      the ovary for small (< 4 mm), large (> 8 mm) and total follicles but not for
      medium sized (4-8 mm) follicles.

PMID- 9231257
TI  - Retention of functional characteristics by bovine oviduct and uterine epithelia
      in vitro.
AB  - The composition of fluids within the bovine oviduct and uterine lumen, important
      in fertilisation and early embryonic development, is ultimately determined by the
      transport properties of the epithelial cells which line the lumen. A preparation
      has therefore been devised to study the role of these cells in oviduct and
      uterine fluid formation. Pure preparations of epithelial cells, as judged
      immunocytochemically, were isolated by enzyme digestion, and grown on collagen
      filters in primary culture. The cells re-establish intercellular junctions to
      form a confluent epithelial layer. Serial samples from the apical and basal media
      were analysed for K+, Na+, Ca2+, glucose and lactate. Bovine oviduct epithelial
      cells maintained gradients of K+ and Ca2+ (apical > basal) for up to 14 days
      after confluence, while bovine uterine epithelial cells maintained apical > basal
      gradients of K+. Both types of epithelium exhibited a small transepithelial
      electrical potential difference and a higher uptake of glucose and production of
      lactate in the basal, as opposed to apical medium. There were no consistent
      differences in any of these parameters with the stage of the oestrous cycle at
      which the cells were removed. The data indicate that bovine oviduct and uterine
      epithelia may be isolated and grown as polarised layers in primary culture. The
      preparations will now enable the mechanisms underlying the secretion of ions and
      non-electrolytes to be determined.

PMID- 9231260
TI  - Effect of selenium on cultured bovine luteal cells.
AB  - The present study examined the possibility that selenium (Se) directly affects
      the corpus luteum (CL) and contributes to the maintenance of reproductive
      function. Primary culture of bovine CL was used to investigate this possibility.
      Se addition from 5 to 200 ppb elevated progesterone concentration of the culture
      medium in a dose-dependent manner which was associated with an increase in cell
      proliferation rather than an increase in progesterone production per cell, and
      decreased the lipid peroxide content of luteal cells. However, the luteal cells
      in which hormone production was increased by LH treatment, accumulated more lipid
      peroxide than in control incubations. The results suggest that Se is involved in
      the degradation of lipid peroxides which are by-products of active progesterone
      production by luteal cells. The increase of cell proliferation observed in this
      experiment was associated with the removal of these toxic peroxides.

PMID- 9231259
TI  - Effect of 48 h treatment with 17 beta-oestradiol or progesterone on follicular
      wave emergence and synchrony of ovulation in Bos indicus cows when administered
      at the end of a period of progesterone treatment.
AB  - The objective of this study was to determine the effect of treatment with
      additional progesterone (P4) or 17 beta-oestradiol (E2) at the end of a period of
      P4 treatment on ovarian follicular development, ovulation time, and plasma
      gonadotrophin and steroid hormone concentrations of Bos indicus cows. Initially,
      two injections of PGF2 alpha were given 14 days apart, and at the time of the
      second injection (Day 0) all cows received a single P4-releasing controlled
      internal drug release (CIDR) device that was removed 10 days later. Control cows
      (Group 1, n = 8) received no other treatment. On Day 8, cows in Group 2 (n = 8)
      and Group 3 (n = 8) received either a s.c. implant containing E2, or a second
      CIDR device, respectively. All CIDR devices and E2 implants were removed at a
      similar time on Day 10. Treatment with E2 or P4 delayed mean (+/- SD) time of
      ovulation (113.1 +/- 25.6 h, 153.4 +/- 44.5 h and 150.8 +/- 25.1 h for Groups 1,
      2 and 3, respectively; P < 0.05) and the mean time (+/- SD) of the luteinising
      hormone (LH) peak (87.4 +/- 24.5 h, 124.3 +/- 45.0 h and 122.3 +/- 25.04 h for
      Groups 1, 2 and 3, respectively; P < 0.05). Both treatments delayed the mean (+/-
      SD) day of emergence of the ovulatory follicle (7.7 +/- 3.6 days, 11.3 +/- 1.7
      days and 11.1 +/- 1.5 days for Groups 1, 2 and 3, respectively; P < 0.05), and
      reduced the variability in the day of emergence of the ovulatory follicle (P <
      0.05) compared with the control cows. Variability in age and duration of
      dominance of the ovulatory follicle was greater in control animals compared with
      treated animals (P < 0.05). Treatment with E2 on Days 9 and 10 did not alter mean
      concentrations of gonadotrophins in the cows in Group 2 compared with control
      cows (P > 0.05), whereas treatment of cows with an additional CIDR device
      resulted in greater mean concentrations of FSH and lesser concentrations of LH on
      Day 9 (P < 0.05) compared with cows in Groups 1 and 2. By Day 10 mean
      concentrations of gonadotrophins were similar among cows in all three groups.
      Concentrations of E2 were less in cows in Group 3 compared with cows in Groups 1
      and 2 from Day 9 to Day 11 (P < 0.05). We conclude that treatment with either E2
      or P4 can influence the pattern of ovarian follicular development and ovulation
      in cattle; however, the mechanism of action of the two treatments may differ.
      Atretogenic treatments for ovarian follicles applied at the end of a period of
      progesterone treatment did not improve synchrony of ovulation.

PMID- 9231261
TI  - Use of a GnRH antagonist in conjunction with low amplitude, high frequency LH
      pulses to induce follicular growth without an LH surge and ovulation in ewes.
AB  - The present study was undertaken to develop an experimental sheep model which
      could be used to investigate the abnormal follicle growth that is associated with
      the absence of the LH surge. On Day 10 of the oestrous cycle, 16 ewes were
      treated with an analogue of prostaglandin (cloprostenol; PG) and blood sampled
      every 4 h thereafter to determine the normal timing of the preovulatory LH surge.
      Three oestrous cycles later, all ewes were simultaneously treated with PG and a
      gonadotrophin-releasing hormone (GnRH) antagonist ([Ac-DNal1, D4C1Phe2, DTrp3,
      DArg6, DAla10] GnRH.HOAc; 50 micrograms kg-1 subcutaneously). Group 1 ewes (n =
      6) received no further treatment. Group 2 ewes (n = 5) were additionally treated
      for a total of 7 days, starting at the time of PG injection, with purified ovine
      luteinising hormone (LH; preparation P 3 R3-5; equivalent to 1.25 micrograms NIH
      oLH-S26) administered i.v. over a 2 min period. For the first 24 h, LH was given
      at 3 h intervals for 12 h, then every 2 h for 12 h, and thereafter hourly for 6
      days. Group 3 ewes (n = 5) were treated as Group 2 but at 72 h received an
      additional antagonist injection (50 micrograms kg-1 subcutaneously). Mean values
      of LH from 24 to 96 h were significantly lower in untreated controls and Group 1
      than in the other two groups (0.58 +/- 0.2 ng ml-1 and 0.55 +/- 0.2 ng ml-1 vs.
      1.63 +/- 0.5 and 1.68 +/- 0.6 ng ml-1, respectively; P < 0.01). After treatment
      with PG alone in the untreated control group, the preovulatory LH surge began in
      all ewes at 59.9 +/- 2.8 h after PG. All Group 1 ewes also had an LH surge but
      the period from PG injection to the onset of the surge was 124 +/- 17.3 h (range
      96-152 h). Only two of the Group 2 ewes had an LH surge (at 160 and 168 h,
      respectively) and no surge was detected in Group 3 ewes. In Group 1, mean values
      of follicle-stimulating hormone (FSH; 0.78 +/- 0.07 ng ml-1) were not affected by
      treatment with antagonist alone; however, in the two groups receiving exogenous
      LH pulses there was a marked decrease in FSH concentrations during the period 24
      96 h. Progesterone concentrations increased 9 days after PG treatment in five out
      of six ewes in Group 1. In Group 2, there was evidence of a variable
      luteinisation response, but in Group 3 progesterone remained less than 0.08 ng ml
      1 throughout. Endoscopy 112-115 h after PG confirmed that none of the 16
      antagonist-treated ewes had ovulated; an event normally expected approximately 80
      h after PG in sheep. The experimental protocol of Group 3 provides the basis for
      a model which will enable examination of the long-term functional capacity of
      ovarian follicles which have not been exposed to an LH surge.

PMID- 9231262
TI  - Alterations in follicular maturation associated with within-breed variation in
      ovulation rate in Chios sheep.
AB  - Within-breed comparisons may be helpful to identify, in a given genetic
      background (Chios sheep), ovarian strategies and control mechanisms associated
      with altered ovulation rate. High and low ewes were identified from two large
      groups (n = 27 and n = 33 in Exp. 1 and Exp. 2 respectively) of Chios ewes
      submitted to repeated laparoscopies (24 times in Exp. 1 and six times in Exp. 2).
      High ovulatory ewes (n = 6 and n = 7 in Exp. 1 and Exp. 2 respectively) had mean
      ovulation rates of 4.3 (Exp. 1) and 4.2 (Exp. 2) while low ovulatory ewes (n = 6
      and n = 7 in Exp. 1 and Exp. 2 respectively) had mean ovulation rates of 2.5
      (Exp. 1) and 1.9 (Exp. 2). In Exp. 1, follicular function was compared in these
      two groups of ewes using follicles obtained at 30 h following luteolysis in the
      same ewes before and after unilateral ovariectomy (ULO). In Exp. 2, circulating
      follicle stimulating hormone (FSH) concentrations were measured from the end of
      the luteal phase up to the preovulatory surge in high and low ewes. Thereafter,
      to demonstrate a causal link between high FSH and high ovulation rate, pituitary
      downregulation was achieved by a 17-day gonadotrophin releasing hormone (GnRH)
      agonist treatment and the ovarian response to similar amounts of exogenous
      gonadotrophins compared between high and low ewes. Numbers of oestrogenic (in
      vitro oestradiol > 250 pg ml-1 h-1) follicles on the first ovary removed (Exp. 1)
      were 2.16 +/- 0.5 vs. 1.33 +/- 0.17 in high and low ewes (P = 0.1). Following
      ULO, these numbers were 3.33 +/- 0.33 and 2.5 +/- 0.18 (P < 0.05 between high and
      low ewes). There were no significant differences between the first and second
      ovaries for any of the parameters studied. Follicles from high ovulatory ewes (n
      = 33) differed from those of low ovulatory ewes (n = 23) by a smaller size (P <
      0.01), a reduced number of granulosa cells (P < 0.01) together with decreased
      oestradiol (P < 0.05) and testosterone (P < 0.01) production in vitro. However,
      steroid production per cell (oestradiol per granulosa cell, testosterone per
      thecal cell) was similar in the two groups of sheep. FSH concentrations (Exp. 2)
      in high ovulatory ewes were significantly higher than those of low ovulatory ewes
      during the late luteal phase, and the decrease in FSH concentrations was steeper
      (1.4 ng) during the early follicular phase for high ovulatory ewes than low
      ovulatory ewes. Chemical hypophysectomy achieved by a 17-day treatment with a
      GnRH agonist demonstrated that these high FSH concentrations may be important to
      generate the high ovulation rate of the 'high' ewes as ovulation rate of high and
      low ewes was similar following chemical hypophysectomy followed by administration
      of similar amounts of exogenous gonadotropins to both groups of ewes. It is
      concluded that, despite different genetic control of their high ovulation rate
      (Chios-polygenic; Booroola-major gene), alterations in follicular function and
      its control are very similar in high ovulatory Chios and in FecB carriers.

PMID- 9231263
TI  - Estrus synchronization in dairy goats: use of fluorogestone acetate vaginal
      sponges or norgestomet ear implants.
AB  - The ultimate aim of any estrus synchronization method is to allow artificial
      insemination at a predetermined time after the end of treatment. This requires a
      very tight synchronization of estrus which is not observed in goats after
      administration of the usual fluorogestone acetate (FGA)/prostaglandin (PG) F2
      alpha/equine chorionic gonadotrophin (eCG) treatment. The possibility to improve
      the synchronization of estrus and luteinizing hormone (LH) peak with different
      progestagens (FGA versus norgestomet) and routes of administration (vaginal
      sponge versus subcutaneous ear implant) was evaluated in two experiments where
      goats received one of three progestagen treatments: (1) a vaginal sponge
      impregnated with 45 mg of FGA, (2) a half-implant of norgestomet, or (3) a whole
      implant containing 3 mg of norgestomet. The progestagens were left in place for
      11 days and intramuscular injections of 400 or 500 IU of eCG (according to milk
      yield) and 50 micrograms of an analogue of PGF2 alpha (cloprostenol) were given
      48 h prior to progestagen removal. In Experiment 1, 117 cycling goats were
      checked for the time of onset of estrus, preovulatory LH peak and ovulation rate
      following estrus synchronization treatment. Goats treated with half-implants came
      into estrus earlier than those receiving vaginal sponges (27.8 +/- 5.0 h vs. 33.0
      +/- 6.6 h, respectively; P < 0.05). No effect of progestagen priming was observed
      on the variability of the onset of estrus. However, the interval between the time
      of onset of estrus and LH peak was more variable (P < 0.05) in goats treated with
      half-implants. In Experiment 2, 170 non-cycling goats were monitored for the time
      of onset of estrus, percentage of females ovulating, fertility and prolificacy
      after estrus induction treatment and artificial insemination with frozen-thawed
      semen performed 24 h after the onset of estrus. No effect of progestagen
      treatment was observed either on the time or the variability of onset of estrus.
      The percentage of goats ovulating and overall fertility rate were higher (P <
      0.05) in goats receiving vaginal sponges (98.2% and 75.0%, respectively) than
      those treated with half-implants (81.8% and 45.5%, respectively). However, no
      significant difference was observed, for the same parameters, in animals
      receiving implants (86.3% and 58.8%, respectively). In conclusion, estrus
      synchronization with a norgestomet implant or half-implant did not reduce the
      variability in the onset of estrus and LH peak. The fertility tended to be lower
      in goats treated with a whole implant and was significantly decreased in goats
      which received a half-implant.

PMID- 9231264
TI  - Restricting maternal space during parturition in the pig. Effects on oxytocin,
      vasopressin and cortisol secretion following vagino-cervical stimulation and
      administration of naloxone.
AB  - This experiment studied the effects on endocrine and birth parameters of
      parturient pigs produced by restricting maternal freedom of movement without
      otherwise altering environment. Six primiparous pigs (gilts) were each given a
      jugular catheter under anaesthesia 7 days before parturition and commenced birth
      in a strawed pen, 2.0 m x 1.5 m in size. Continuous automated blood sampling (3
      ml min-1) from unrestrained gilts began following the birth of the first piglet
      (stage 1) and continued for 2 h. After at least 30 min of blood collection,
      maternal space was reduced to 2.0 m x 0.55 m by placing rails across the pen
      (stage 2). The scope for movement in stage 2 was similar to that offered by a
      farrowing crate. After at least 25 min each gilt was given the opioid antagonist
      naloxone (1 mg kg-1 i.v.: stage 3). At each stage, vagino-cervical stimulation
      (VCS) was applied to mimic foetal ejection. Non-cervically stimulated oxytocin
      (OT) secretion between stages 1 and 2 was unchanged (P > 0.05) but increased
      significantly relative to both stages 1 and 2 following naloxone treatment for 15
      20 min (P < 0.05, paired t-tests on log10 data). Following VCS in all stages
      plasma OT rose (P < 0.05) for 1-2 min in a similar way to that seen previously
      following foetal ejection, the increases being proportionally similar
      irrespective of stage or baseline secretion. Cortisol secretion did not increase
      as a consequence of space restriction (mean +/- SEM concentrations were 28.6 +/-
      8.51 pmol l-1 and 32.3 +/- 11.8 pmol l-1 in stages 1 and 2, respectively). In
      addition, VCS did not significantly affect cortisol output. Lysine vasopressin
      concentrations were not affected as a consequence of either stage or VCS.
      Parturition was not interrupted following space restriction of gilts. These data
      suggest that reducing maternal space allowance during parturition is not
      stressful when the process does not involve the movement of animals to novel
      surroundings.

PMID- 9231266
TI  - Failure of melatonin implants to alter onset of puberty in gilts.
AB  - Forty crossbred gilts (Hampshire x Yorkshire x Landrace x Duroc) weighing 55.4 +/
      0.5 kg at 4.2 +/- 0.1 months of age received either melatonin implants (N = 20)
      or served as controls (N = 20). Gilts were housed in a temperature controlled
      room (21 degrees C) with a light (L):dark (D) cycle of 10L:14D. Initially, four
      implants (12 mg melatonin each, Wildlife Pharmaceuticals, Ft. Collins, CO) were
      placed in one ear subcutaneously. At 2-week intervals, five, six, seven or eight
      implants were placed in ears of the gilts (one implant per 11.8 kg body weight).
      Throughout the trial, blood samples were collected twice weekly by jugular
      venipuncture. All gilts were exposed to mature boars for 15 min on alternate
      days. Age of puberty was determined from serum concentrations of progesterone and
      visual observations of estrus. Serum concentrations of melatonin were elevated (5
      10 fold) throughout the trial in those gilts that received melatonin implants.
      Average daily gain (P = 0.51) and age at puberty (P = 0.57) were similar between
      gilts that received melatonin implants or no implants. Even though gilts
      continued to receive melatonin after they attained puberty, elevated serum
      concentrations of melatonin did not alter the length of subsequent estrous cycles
      (P = 0.90). These data indicate that elevation of serum concentrations of
      melatonin via implants did not alter the onset of puberty or length of subsequent
      estrous cycles.

PMID- 9231265
TI  - Insulin-like growth factor-I in the porcine endometrium and placenta:
      localization and concentration in relation to steroid influence during early
      pregnancy.
AB  - To initiate the establishment of an epitheliochorial placenta, the developing
      porcine conceptuses contact the maternal endometrium on its mesometrial side. The
      porcine conceptuses secrete estrogens which, together with circulating maternal
      hormones, govern variations in the structure as well as expression and levels of
      steroid receptors and growth factors during early pregnancy. Mesometrial samples
      of endometrium or placenta were collected from 15 early pregnant (8-30 days after
      the onset of estrus) and six cycling (days 1-14) gilts. The variations in tissue
      morphology and immunohistochemical localization of insulin-like growth factor-I
      (IGF-I) were related to the tissue levels (by enzyme immunoassay) of receptors
      for estrogen (ER) and progesterone (PR), as well as mRNA (by solution
      hybridization) concentrations for the two receptors and IGF-I. IGF-I
      immunoreactivity was present in samples from all animals, being principally
      located in maternal epithelium, trophoblast, endothelium and vascular smooth
      muscle; the latter showing the strongest labeling. The levels of receptor
      proteins, as well as mRNAs, were highest in the non-pregnant animals at estrus
      and metestrus. The pregnant animals showed decreasing concentrations to
      consistently low levels after day 14. Temporal changes in the studied parameters
      were clearly coincidental with the peak (days 13-14) in conceptus estrogen
      secretion, e.g. the more uniform IGF-I immunolabeling in the uterine glands (days
      8-13) compared with the later stages studied; the conspicuous accumulation and
      release of secretory vesicles in the endometrial glands (days 8-13), marking the
      change in secretory quality and quantity, leading to a gradual shift from
      histotrophic to hemotrophic nutrition of the conceptuses, and finally, the
      peaking level of IGF-I mRNA in the pregnant endometrium (days 12-13) which
      decreased considerably thereafter. It is concluded that IGF-I activity in the
      porcine uterus changes with the early development of the placenta.

PMID- 9231267
TI  - Superovulation in llamas (Lama glama) with pFSH and equine chorionic
      gonadotrophin used individually or in combination.
AB  - The purpose of this experiment was to evaluate the efficacy of pFSH and/or equine
      chorionic gonadotrophin (eCG) for inducing superovulation in llamas. Sixteen
      adult llamas weighing on average 130 kg (range 110-140) and which had been
      showing signs of oestrus for 5 days were randomly allocated to three treatment
      groups and one control group (n = 4). Llamas in Group A received eCG (500 IU,
      i.m.) once daily for 3 days, those in Group B received pFSH i.m., in decreasing
      doses every 12 h for 5 days for a total of 220 mg, while those in Group C
      received eCG (500 IU, i.m.) once, and pFSH (total of 156 mg, i.m.) in decreasing
      doses for the next 4 days. Llamas in Group D (control) received saline (5 ml,
      i.m.) every 12 h for 5 days. All llamas were allowed to be mated on the evening
      of Day 5 and were given hCG (750 IU, i.m.) at that time; a second mating was
      carried out 12 h later. A non-surgical ova/embryo collection technique was
      performed 7 days after the first mating and then the ovarian response was
      evaluated by way of laparoscopy. All 16 llamas were mated successfully. The mean
      (SEM) number of ovulations (7.3 +/- 3.1) in Group B was significantly higher (P <
      0.05) than in the other groups (1.5 +/- 0.5, 2.0 +/- 0.7, and 0.3 +/- 0.3 for
      groups A, C and D, respectively). The number of follicles > 10 mm at the time of
      ova/embryo collection was significantly higher (P < 0.05) in the groups treated
      with eCG. A total of 21 ova/embryos was recovered from the all flushed llamas,
      corresponding to 47.7% of corpora lutea observed. Of the 21 ova, 15 were
      fertilised; 13 of those were classified as excellent blastocysts and the
      remaining 2 were classified as dead or degenerating. Results demonstrate that
      llamas can be successfully ovarian superstimulated while expressing behavioural
      oestrus and suggest that pFSH is more effective than eCG to induce
      superovulation.

PMID- 9231268
TI  - Seasonal effects on gestation length and birth weight in alpacas.
AB  - Gestation lengths and birth weights were measured in 162 pregnancies in alpacas
      (Lama pacos) farmed in the high country of the South Island of New Zealand. A
      comparison of pregnancies from spring (mid-October to mid-December) and autumn
      (mid-February to late April) matings showed that gestation lengths were 12.5 days
      longer in spring (348.9 +/- 1.4 days vs. 336.4 +/- 1.2 days; P < 0.0001). For
      each day later in spring that a female was mated there was an increase in
      gestation length of 0.11 days (P < 0.05), whereas for each day later in autumn
      the gestation was reduced by 0.24 days. There were no significant effects of sex
      of cria or age of dam on gestation length. After adjustment for gestation length,
      crias born in autumn weighed 1.0 kg more than those born in spring (8.8 +/- 0.15
      kg vs. 7.8 +/- 0.18 kg: P < 0.001). Female crias weighed 0.4 kg less than males
      at birth (P < 0.05). The results suggest that in this environment it will be
      difficult to maintain spring-mated females in a 12 month breeding cycle.

PMID- 9231269
TI  - Fertility of the male alpaca: effect of daily consecutive breeding.
AB  - The fertility of the male alpaca under different frequencies of daily consecutive
      matings was evaluated. Fifteen adult male Huacaya alpacas were divided randomly
      into three groups of five each to breed lactating female alpacas. The schedule of
      daily matings was two, four and six consecutive breeding per group and for nine
      consecutive days. Ovulation was determined by progesterone at seven days after
      breeding. Pregnancy was determined by ultrasonography at 15 and 30 days after
      breeding. Two hundred and eighty females were bred with some males not fulfilling
      their schedule of breeding. There were differences (P < 0.05) in the fertility
      rate of males breeding two and four times daily (76%) in contrast to 59% for
      males breeding six times. There were also differences (P < 0.05) in the fertility
      of individual males. Length of copulation was affected (P < 0.05) by schedule of
      matings, day of breeding and male. Ovulation was independent of length of
      copulation. Overall, it seems the fertility of the male alpaca is affected
      significantly when consecutive matings are over four times a day and for nine
      consecutive days.

PMID- 9231270
TI  - Effect of sperm count on the fertility and prolificity rates of meat rabbits.
AB  - The effect of sperm count per insemination dose was evaluated on fertility and
      litter size at birth. In the first experiment, 124 receptive multiparous does
      were inseminated with 16, 4, 2 and 1 million spermatozoa. Does were slaughtered
      12 days after insemination and the number of implanted embryos were recorded.
      Does inseminated with 16 or 4 million sperm showed no differences in pregnancy
      rate (90%) and number of implanted embryos (10.7). Does inseminated with 2
      million sperm had a lower pregnancy rate (66%, P < 0.05) and does inseminated
      with 1 million sperm had lower fertility (23%, P < 0.05) and number of implanted
      embryos (4.9, P < 0.05). In the second experiment, 395 receptive does in
      different reproductive status were inseminated with 16 or 4 million spermatozoa.
      No differences were found in fertility (74%) and litter size at birth (9.0). No
      interactions between sperm count and reproductive status were observed.

PMID- 9231271
TI  - Pastoral care and moral government: early nineteenth century nursing and
      solutions to the Irish question.
AB  - This paper re-examines the role of the early nineteenth century nurses,
      conventionally depicted in nursing histories as the well-meaning but untrained
      Catholic nursing nuns or, in post-Reformation Europe, servants and fellow
      patients. It will be argued here that professional and capable nursing had begun
      to transform the care of the sick poor and to demonstrate its importance to the
      success of medical/surgical innovation long before Florence Nightingale and her
      call to Scutari. Moreover, the case is put that the emergence of nineteenth
      century forms of care for the sick occurred in response to the pressing problems
      of population management in Ireland, Great Britain and North America. The
      pastoral concerns of the first Irish nurses, with their expertise in both the
      spiritual and material domains, provided the prototype for what was to follow: a
      spiritual form of life that addressed the governmental concerns of its time.
      Finally, it is argued that given the overt moral imperatives of nineteenth
      century nurses of all persuasions, the depiction of nursing history as a crossing
      from the religious to the secular domain is challenged.

PMID- 9231272
TI  - Integration of therapeutic approaches: a new direction for mental health nurses?
AB  - In this paper, the author reviews the value of the taking up of a specific
      therapeutic school or base for practice in mental health nursing, such as
      cognitive behavioural therapy or client-centred therapy. This is examined against
      a background of increased interest in non-'purist' forms of therapeutic approach
      in the fields of psychotherapy and counselling. The common factors present in
      effective helping relationships are highlighted, along with a way of
      understanding the fundamental form of a given helping relationship which is
      perhaps independent of theoretical orientation. Thinking in this mode cuts across
      traditional 'models of nursing/therapy' speak. This may allow the mental health
      nurse to adopt appropriate client-need-driven interventions, which are not
      hamstrung by theoretical dogma. Given this, the paper suggests an 'honourable
      position' of eclecticism for mental health nurse education and practice.

PMID- 9231273
TI  - Psychiatric nurses' satisfaction: the effects of closure of a hospital.
AB  - A survey by questionnaire was carried out to examine the level of nursing staff
      satisfaction with the acute psychiatric services. Comparisons were made between
      views of older psychiatric hospitals and newer district general hospital units,
      and before and after the closure of Friern Barnet Hospital, London, England when
      the service was reorganized to include fewer beds. The importance of nurses
      having their say is emphasized, and areas in which improvements can be made are
      suggested.

PMID- 9231274
TI  - A longitudinal study of feeding difficulty and nursing intervention in elderly
      patients with dementia.
AB  - Structural equation modelling has already been used to study the relationship
      between feeding difficulty and nursing intervention in elderly people with
      dementia. Four models were tested and one provided an acceptable fit to the data.
      However, there were limitations in terms of sample size and the scales used to
      measure the variables related to feeding difficulty and nursing intervention. In
      the present study the sample size has been increased and the scaling of variables
      has been improved and an additional model has been tested. The best fitting model
      introduces a latent state variable to explain the relationship between feeding
      difficulty and nursing intervention. In order to study this relationship further
      several lines of investigation are suggested, including trait validation and
      state experimentation. These will be explained in the paper.

PMID- 9231275
TI  - Attitudes towards mental illness: testing the contact hypothesis among Chinese
      student nurses in Hong Kong.
AB  - This study investigated whether previous contact with mental illness affected the
      attitudes to mental illness (AMI) of general student nurses in Hong Kong-the
      contact hypothesis. We employed a quasi-experimental design. We compared the
      attitudes to mental illness of students who had previous contact with mental
      illness through having taken a psychiatric secondment with those who had not
      taken a psychiatric secondment. Also, we compared the AMI of: students who had
      taken other courses related to mental illness with those who had not; those who
      had a family history of mental illness with those who had not; and those who
      lived with a mentally ill relative with those who did not. We found that previous
      contact with mental illness had no significant effect on the attitudes to mental
      illness of the students. In other words our findings do not support the contact
      hypothesis. Our sample expressed positive general attitudes to mental illness
      when presented with general issues about mental illness. However, their attitudes
      were less positive when presented with specific issues about mental illness that
      might impinge upon their daily lives. We discuss the implications of these
      findings for mental health nursing practice, education and research.

PMID- 9231276
TI  - Finnish public health nurses' experiences of primary health care based on the
      population responsibility principle.
AB  - Implementation of a 'population responsibility' principle in Finnish health
      centres began in the late 1980s. The aim of this study was to describe public
      health nurses' (PHNs') experiences of primary health care based on this principle
      and to identify contextual and personal factors related to their experiences. The
      sample consisted of PHNs in 10 health centres. A questionnaire was developed
      based on a qualitative study. The survey was conducted in 1990 and repeated in
      1992. The response rate was 84% for the 1990 sample (n = 102) and 91% for the
      1992 sample (n = 131). In the multivariate analysis of variance type of community
      (urban/rural), size of the target population, task division model and existence
      of regular teamwork between social and health care personnel were chosen as
      contextual factors studied. Age, length of professional experience and having
      specialist education in midwifery were chosen as personal factors. Dependent
      variables were subscales on: experiences of planning and implementation,
      perceived influence of population responsibility on nurse-client relationships,
      comparison with previous experiences, views and experiences on comprehensiveness
      of care and job satisfaction. The majority of the PHNs experienced only minor
      changes in their work after the implementation of population responsibility. They
      were most critical about the way these changes were planned and implemented.
      Changes were mainly perceived as positive. There were some differences in the two
      samples, reflecting a shift from both positive and negative responses towards
      more neutral or more positive responses. Several contextual factors were multi
      dimensionally related to the PHNs' experiences.

PMID- 9231277
TI  - Illuminating environmental influences on women's caring.
AB  - Current health care reform is resulting in increasing demands on women to care
      for others. Little is known about the process of women's caring or the effects of
      caring on women. This feminist grounded theory study resulted in a substantive
      theory that explains how women manage the problematic aspects of caring and
      explicates the ways that environment influences women's responses to caring
      demands. Of particular concern is the evidence that the existing social structure
      creates and intensifies problems for women caring. The discussion considers the
      implications of the findings for health policy and nursing practice.

PMID- 9231278
TI  - Information needs of women during early treatment for breast cancer.
AB  - This study assessed the information needs of 70 women with breast cancer being
      treated by surgery, chemotherapy or radiation therapy. Information needs were
      measured by the breast cancer version of the Toronto Informational Needs
      Questionnaire (TINQ-BC). All women had high information needs, irrespective of
      type of treatment received. They mainly wanted information about their disease,
      treatments and investigative tests. An examination of individual items on the
      TINQ-BC revealed that all women wanted information about recurrence, specifically
      they wanted to know if the cancer would come back and how to tell if it had
      recurred. The results provide nurses with some direction as to what information
      to give women receiving early treatment for breast cancer.

PMID- 9231279
TI  - Vulnerability, health and health care.
AB  - The concept of vulnerability is an important one for nurses because of its
      implications for health. The experience of vulnerability creates stress and
      anxiety which affects physiological, psychological and social functioning.
      Although everyone is vulnerable at different times in his or her life, some
      individuals are more likely to develop health problems than others. Vulnerability
      is affected by personal factors as well as factors within the environment. Trends
      in society indicate that increasing numbers of vulnerable people will create
      additional demands on an already over-burdened health care system. Vulnerability
      is an area that requires much further research and application.

PMID- 9231280
TI  - Assessment of quality of life with the Nottingham Health Profile among patients
      with coronary heart disease.
AB  - The aim was to describe the quality of life of people suffering from coronary
      artery disease. The patients had been treated with medication (n = 80),
      percutaneous transluminal coronary angioplasty (n = 100) and coronary artery
      bypass surgery (n = 100). Of the 280 patients, 189 were men and 91 women. The
      patients who participated in this study were seriously ill, as nearly half of
      them had three or more stenosed coronary arteries. Male patients were most
      numerous in the bypass surgery group and female patients in the angioplasty
      group. The quality of life was evaluated using the Nottingham Health Profile
      (NHP) instrument relation to an age- and sex-matched general population, the
      background factors and the severity of the coronary disease. The NHP
      questionnaire consists of 38 statements on health problems, making up six
      dimensions of subjective health: physical mobility, pain, sleep, energy,
      emotional reactions and social isolation. The health-related quality of life of
      coronary patients before the invasive procedures was significantly poorer on all
      the six dimensions than the quality of life in an age- and sex-matched general
      population. The most obvious differences were seen on the following dimensions:
      energy, pain, emotional reactions, sleep and physical mobility. The smallest
      differences occurred in social isolation. Both males and females had the lowest
      value for energy and social isolation in the youngest age group (35-54 years).
      The index values of emotional reactions in the two youngest groups were
      significantly higher among females than males, which reflects poor quality of
      life. The women in the age group of 35-54 years found the manifestation of a
      serious disease extremely hard to face. Our findings clearly suggest that while
      choosing the mode of treatment, the patient's quality of life should be
      considered along with the clinical severity of the disease, especially in the
      case of young women. From the societal and social points of view, the patient's
      symptoms and quality of life are even more important than the objective medical
      outcome. In clinical decision-making, the goal is to integrate the results of
      health-related quality of life assessments with clinical decisions, and this
      underlines the need to evaluate whether the treatment given is congruent with the
      patient's quality of life. On the basis of the present findings, the NHP
      instrument seems to be applicable to quality of life measurements among coronary
      patients. It does not, however, necessarily give an accurate and profound view of
      an individual's overall quality of life.

PMID- 9231282
TI  - Understanding nurses' communication with patients in accident & emergency
      departments using a symbolic interactionist perspective.
AB  - Much research has examined the nature and duration of nurse-patient
      communication. However, few studies sufficiently acknowledge the extent to which
      communication is influenced by the meanings and perceptions of those involved or
      the social context in which it occurs. This paper reports on a study which used
      in-depth interviews with 21 nurses in two accident and emergency departments to
      explore how their perceptions of their work and patients influenced communication
      and the way in which patients' anxieties were addressed. A grounded theory
      approach was used to guide the process of data collection and analysis, and
      interpretation of findings discussed with reference to a symbolic interactionist
      perspective. The core category was identified as 'Defining the role of the
      accident and emergency department nurse'. This category illuminates the nurses'
      perception of their role and purpose as being primarily concerned with dealing
      with emergencies and providing urgent physical care. Two other categories,
      'Nurses' priorities and patients' anxieties' and 'Keeping the department running
      smoothly', delineate the impact this view had on the organization and delivery of
      nursing care in accident and emergency departments and its effect on nurse
      patient communication.

PMID- 9231281
TI  - Patients' perceptions of the pre-operative information they need about events
      they may experience in the intensive care unit.
AB  - Through a descriptive survey, this study examined the pre-operative information
      which patients need about the events they may experience in intensive care, when
      they are admitted there following elective surgery. A subsidiary aim was to find
      out how they felt this information should be delivered. Questionnaires were
      posted to a convenience sample of 57 people who had been admitted post
      operatively to one ICU in the past year. Forty-three (75%) of the questionnaires
      were returned and were analysed with the five returned in the pilot study. The
      results suggested that pre-operative information about ICU was perceived helpful
      by all respondents, particularly the management of pain and nausea, the likely
      site of pain, mouth care, the high nurse:patient ratio and having a urinary
      catheter. Information rated helpful less frequently, included noise levels,
      visiting times and men and women being nursed in the same room. The most popular
      method for receiving the information was via a pre-operative visit from a nurse
      working in ICU. In view of the sampling procedure and the validity of data
      collection methods, these findings cannot be generalized.

PMID- 9231284
TI  - Learning from errors in nursing practice.
AB  - Little attention is paid to the issue of errors in nursing practice. Staff are
      reluctant to discuss or publicize them. However, as clinical audit and quality
      management become more important and established in the health service, there is
      now a greater need to investigate and monitor the incidence of errors. The
      purpose of this study was to examine the causes and consequences of errors as
      well as the potential for errors to initiate changes in practice. One hundred and
      twenty-nine nurses answered a 22-item questionnaire relating to an error they had
      made. Nurses reported that the most common causes of errors were lack of
      knowledge or information, work overload, stressful atmosphere and lack of support
      from senior staff. Nurses were found to have recourse to a number of coping
      strategies in the aftermath of the error. Accepting responsibility and planful
      problem-solving were found to lead to positive changes in practice, whereas
      distancing and self-controlling strategies were associated with defensive
      changes, particularly with a tendency not to divulge the error. The findings also
      showed that errors had the potential to effect learning. The study suggests the
      need for staff to be encouraged to accept responsibility for their error within
      the framework of support. Strategies should be developed so that errors can be
      managed in a more constructive manner.

PMID- 9231283
TI  - Building a relationship: communications and relationships between staff and
      stroke patients on a rehabilitation ward.
AB  - Communications among staff and patients on a stroke rehabilitation ward form the
      focus of this article, which reports on some aspects of a larger study using a
      grounded theory approach. Tape-recorded interviews were transcribed and analysed
      concurrently according to recommendations for the approach. A main theme entitled
      building a relationship was identified, and this process was found to occur in a
      context varying from participative at one end of a continuum to hierarchical at
      the other. Building a relationship was found to be influenced by role, personal
      qualities and organizational context. Appropriate relationships between role
      holders were subject to negotiation, leading to a resulting congruence or
      incongruence between participants' expectations of each other and their roles.
      Personal qualities were brought into play in the process, with patients' views of
      staff and staff views of patients both being influential. Some of these views
      seemed to parallel what has been described in earlier literature as 'the sick
      role' and the labelling of patients as 'good' or 'bad'. Responses to personal
      qualities led to nurses ascribing meaning to patients' behaviour in terms of
      adjustment to their stroke, giving time to them to help them to adjust, and
      withdrawal and handing over to other staff if this strategy failed.
      Organizational context also had an influence on building a relationship, with
      time constraints being identified particularly by nurses, and the need to fit in
      the most essential aspects of care. Place was also important, in that nurses were
      confined to the ward as a work location, whereas other therapists and doctors
      worked in other places and sometimes had the facility to take patients off the
      ward to concentrate on therapy. The findings are discussed against the background
      of related literature and the conclusion is drawn that the crucial role of nurses
      in rehabilitation is not recognized and valued, and that shortages of resources
      especially suitably qualified and trained nursing staff-are a negative influence
      on building the relationships which are vital to successful rehabilitation.

PMID- 9231285
TI  - The problem of arriving at a phenomenological description of memory loss.
AB  - This paper discusses a methodological difficulty that arose when uncovering the
      conscious experience of being nurtured as an in-patient with depression on a
      psychiatric ward. It considers the problem of arriving at a phenomenological
      description of memory loss in a patient who had undergone electroconvulsive
      therapy (ECT). The paper begins by describing the prevalence of depression and
      its significance for nurses working in in-patient settings. Examples of empirical
      research into memory loss in depression are used to show what researchers must
      set aside if they are to arrive at a phenomenological description of memory loss.
      The choice of a phenomenological approach to the wider study from which the
      methodological problem discussed here arose is then justified. The phenomena of
      memory is introduced to show the methodological significance of attempting to
      arrive at a phenomenological description of the statement made by one of the
      participants, a woman being treated as an in-patient for major depression. A
      possible description of the phenomena of memory loss based on the existential
      phenomenology of Sartre is offered to call into question the ability of
      researchers to bracket their assumptions. The significance for nurses of the
      wider study from which our example is taken is then described. Finally it is
      argued that despite the methodological difficulty described, a phenomenological
      perspective based on the philosophy of Husserl can point nurses in the direction
      of meeting the human needs of their patients.

PMID- 9231286
TI  - A critical review of the belief that technology is a neutral object and nurses
      are its master.
AB  - This paper discusses technology in relation to nursing practice. The purpose of
      the paper is to introduce to nursing literature a critique of an important and
      common assumption concerning the relationship between nurses and technology. The
      discussion centres on the belief that technology is a neutral influence upon the
      practice of nursing. Technology is argued to be more pervasive an influence upon
      the politics of practice, the values of individuals, nursing practice and
      decision making, than many nurses identify. Therefore adequate understanding of
      the relationship between technology and nursing practice must address the need to
      be more critical of the belief that technology is a neutral object, and
      originates from being cognisant of arguments which both support and oppose the
      assertion.

PMID- 9231287
TI  - Adherence: a matter of self-efficacy and power.
AB  - This paper examines the relationship between self-efficacy and social power
      (expert and referent) and how the application of this relationship, leads to
      client adherence and compliance. Referent power is defined, including methods
      that health care professionals may use to develop and apply referent power.
      Expert power is defined and addressed in the context of referent power, self
      esteem and self-efficacy as a means of promoting adherence. Self-efficacy as a
      concept is defined and explored in the context of social power. The relationships
      between self-efficacy and social power (expert and referent) are shown as
      important determinants of adherence and compliance. The theory of the application
      of referent and expert power in relationship with self-efficacy has been compared
      with an effective programme, yielding high compliance, at Western Psychiatric
      Institute and Clinic, showing the theory's relevance and applicability in
      determining compliance. Explored are the reasons for non-compliance in the
      elderly population and how the theory model can remedy these detriments for
      compliance. The empowerment of elderly patients through the application of this
      theory to medication compliance is examined. The determination of adherence and
      compliance is shown by the application of the relationship between self-efficacy
      and both expert and referent power.

PMID- 9231288
TI  - Theory-based nursing practice.
AB  - Theory provides nurses with a perspective with which to view client situations, a
      way to organize the hundreds of data bits encountered in the day-to-day care of
      clients, and a way to analyse and interpret the information. A theoretical
      perspective allows the nurse to plan and implement care purposefully and
      proactively. When nurses practice purposefully and systematically, they are more
      efficient, have better control over the outcomes of their care, and are better
      able to communicate with others. Health care agencies can designate a specific
      nursing theory to guide the nursing practice within the entire organization. The
      critical component in choosing a nursing theory for an organization is the 'fit'
      between the philosophical assumptions of the organization and the theory.
      Modelling and role-modelling, a theory and paradigm for nursing, can be
      implemented in any setting. Hospice is a concept of care, not a place. Hospice
      care illustrates the excellent 'fit' between an existing philosophy of care and
      theory-based nursing practice. The 'fit' is based on the similarity of the
      philosophical assumptions of hospice and the nursing theory of modelling and role
      modelling.

PMID- 9231289
TI  - What should nurse teachers be doing? A preliminary study.
AB  - There is little doubt that the role of the nurse teacher is complex and
      multifaceted in nature. The apparently conflicting demands of NHS trusts and
      education in the United Kingdom, at the time of integration of nurse education
      into the higher education sector, further complicates the role. This recognition
      underlines the need to capture and measure key aspects of nurse teacher function
      in order to maximize educational gain. Using a comprehensive literature review,
      focus group discussions and a small number of individual semi-structured
      interviews, this preliminary study explored the issue of teacher workload, from
      the perspective of the principal stakeholders in nurse and higher education.
      Competing research and clinical practice objectives for nurse teachers are
      identified against a background of changing health care provision, reduced
      availability of placements and an increased need for evidence-based practice.

PMID- 9231290
TI  - Defining quality student feedback in distance learning.
AB  - The quality of student feedback is of critical importance in distance learning.
      Students studying such courses may be geographically far removed from tutors, and
      limited contact opportunities necessitate a sharp and accurate focus upon aspects
      of study which link theory, research, clinical practice and written assessment
      closely together. An understanding of quality feedback begins with an
      appreciation of the role of distance learning course tutors and the education
      models which can usefully guide them. Quality also relies upon a close evaluation
      of support to students as courses are planned, launched and then monitored
      through course boards or their equivalent.

PMID- 9231291
TI  - Project 2000: perceptions of the philosophy and practice of nursing: shifting
      perceptions--a new practitioner?
AB  - This is the first of two papers which address aspects of the findings of a large
      scale study commissioned by the English National Board which set out to examine
      the impact of Project 2000 on perceptions of the philosophy and practice of
      nursing. The findings presented here suggest that there have been fundamental
      shifts in perceptions of the nature and discipline of nursing. Students and
      diplomates of the course perceive themselves as knowledgeable doers, with their
      practice well grounded in theory and research. They value the interpersonal
      skills teaching and place the patient firmly at the centre of care delivery,
      viewing the patient holistically and being prepared to be fierce patient
      advocates where necessary. It is difficult to determine the extent to which these
      shifts can be attributed to the Project 2000 course, although the Project 2000
      approach to education appears to be an important factor.

PMID- 9231292
TI  - The biological sciences in nursing: an empirical paper reporting on the
      applications of physiology to nursing care.
AB  - This action research study was undertaken to address practical concerns over
      curriculum development in nursing. The applied physiology component of a post
      registration nursing diploma was evaluated in terms of its impact on patients
      rather than on the nurses themselves. The reported data were triangulated, all
      the findings indicated that patient care could be enhanced when nurses applied
      their knowledge of physiology to practice. Despite its limitations of scale, this
      study contributes to the curriculum debate in nurse education.

PMID- 9231293
TI  - Attitudes towards the relevance of biological, behavioural and social sciences in
      nursing education.
AB  - This paper explores the perceptions of staff and students regarding the
      supporting sciences within nursing education and how they feel such content
      relates to the 'real world' of nursing. A qualitative study examining the
      perceptions of students and teaching staff, particularly the concept of
      relevance, was conducted to explore factors which impact upon the integration of
      theory and practice. The teaching approaches used, assessment items selected, and
      the perceptions held about what nurses actually do all impinge upon what, and
      how, students learn in subjects which are essentially non-nursing in their
      orientation. Through an awareness of factors affecting how students and teaching
      staff actually approach supporting sciences content, better informed curriculum
      decisions can be made.

PMID- 9231294
TI  - Husserl, phenomenology and nursing.
AB  - Discussions of phenomenological research in nursing consistently appeal to either
      Husserl or Heidegger in justifying the technical and conceptual resources they
      deploy. This paper focuses on Husserl, and examines the relationship between his
      phenomenology and the accounts of it that are to be found in the nursing
      literature. Three central ideas are given particular attention: the
      phenomenological reduction, phenomena, and essence. It is argued that nurse
      researchers largely misunderstand these concepts and that, as a result, their
      version of Husserl's philosophy bears little resemblance to the original. A
      further consequence is that the project of identifying the 'essential structure'
      of a phenomenon, typically adopted by the nurse researchers who cite Husserl as
      an authority, comes close to being unintelligible. It is suggested that, while
      the methods used in 'phenomenological' nursing research may still have some
      legitimacy, they cannot achieve what they are alleged to achieve, and they should
      be detached from the framework of Husserlian ideas and terminology which is
      supposed to justify them.

PMID- 9231295
TI  - Intuition: a critical review of the research and rhetoric.
AB  - This paper will explore the concept of intuition in nursing from an acute care
      and community nursing perspective. It will consider definitions of intuition and
      examine the research which can inform our understanding of this important
      component of decision making. In the current health service climate, which
      demands measurable research-based evidence, the involvement of intuition as an
      element of judgement is often denigrated. The result is that many nurses are
      being forced to be covert in their use of this crucial aspect of judgement and
      focus solely on the conscious elements of decision-making. However, research
      evidence would suggest that intuition occurs in response to knowledge, is a
      trigger for action and/or reflection and thus has a direct bearing on analytical
      processes in patient/client care. The authors therefore argue that the essential
      nature of intuition cannot be ignored in the practice, management, education and
      research of nursing.

PMID- 9231296
TI  - Heuristics, servants to intuition, in clinical decision-making.
AB  - This paper explores intuitive judgements of nurses in clinical decision-making
      situations. The qualities of intuition are presented from both theoretical and
      practical perspectives and attitudes towards intuition from both nurses
      themselves and other health professionals are identified. An heuristic framework
      from cognitive psychology is applied to intuitive aspects of the clinical
      judgements that nurses have made. This interpretation is proposed as a partial
      explanation of intuition, and its use in advancing the understanding of intuition
      is recommended.

PMID- 9231297
TI  - Sociology and the nursing curriculum: a further comment.

PMID- 9231298
TI  - An open study of the effects of sertraline on adolescent major depression.
AB  - This open study investigated the effects of sertraline in treating 13
      adolescents, ages 12 to 18, who were hospitalized for treatment of a major
      depressive episode. The sample included 7 adolescents with nonendogenous
      depression and 6 with endogenous depression, as diagnosed by both Research
      Diagnostic Criteria (RDC) and Kiddie-SADS-P DSM-III-R endogenous subtype
      criteria. These patients were followed for an inpatient length of stay ranging
      from 9 to 38 days (mean 19 days), with later outpatient follow-up for a total of
      12 weeks. Measures of depression were found to improve significantly, including
      suicidal ideation and most of the DSM-III-R symptoms of major depression.
      Sertraline (mean 110 mg or 1.96 mg/kg daily) significantly decreased scores on
      the 24-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression
      Rating Scale from premedication baseline to treatment week 12, and also between
      weeks 1 (after a large week 1 improvement, presumably due to nondrug effects) and
      12. There was a small but significant improvement on the Children's Global
      Assessment Scale between baseline and week 12, but the Family Global Assessment
      Scale showed no significant change; neither global assessment scale showed
      significant effects between weeks 1 and 12. Sleep disturbance was common (69%)
      after 12 weeks of treatment, but clinically significant improvements in sleep
      patterns were also observed. This open-label prospective study suggests that
      sertraline might be useful in treating adolescents with major depression. Adverse
      effects, mainly insomnia and drowsiness, were relatively common but usually
      manageable. One patient developed mania after 8 days of sertraline treatment at a
      dose of 100 mg daily.

PMID- 9231299
TI  - Management of blood-drawing fears in adolescents with comorbid anxiety and
      depressive disorders.
AB  - As more pharmacologic treatment and research on child and adolescent psychiatric
      patients are conducted, the common problem of blood-drawing fears will need to be
      addressed. Avoidance of blood-drawing could jeopardize an individual's physical
      and mental health, and inhibit the collection of data aimed at furthering the
      study of psychiatric disorders in youth. This report describes the naturalistic
      application of specific techniques for managing severe blood-drawing fears in
      adolescent subjects undergoing a clinical trial. The adolescents (ages 12-18)
      were 44 consecutive school refusers with comorbid anxiety and major depressive
      disorders. Of the school-refusing adolescents, 27% (12 of 44) were observed to
      have a severe fear of blood-drawing. A management strategy comprised of providing
      information, distraction, supportive reassurance, and exposure appeared
      successful in managing the fears of blood-drawing in all of the adolescents,
      except two. These 2 adolescents refused to enter the treatment study due to a
      marked fear of blood-drawing. All 10 subjects who exhibited a fear of blood
      drawing and were able to complete the initial blood test, using the interventions
      noted, were able to obtain subsequent venipunctures with minimal or no avoidance
      behavior. These preliminary findings suggest that blood-drawing fears can be
      effectively managed in most cases, though controlled studies of these
      interventions are needed.

PMID- 9231301
TI  - Use of risperidone in psychotic disorder following ischemic brain damage.
AB  - Risperidone, a novel atypical neuroleptic agent, was used to treat a psychotic
      disorder secondary to ischemic brain damage in a 19-year-old adolescent, who had
      been treatment-refractory to two conventional antipsychotic agents and valproate.
      Clinically significant reductions in behavioral agitation and psychotic thinking
      initially appeared within the first 4 days of treatment with risperidone 3 mg
      twice daily. Risperidone was well tolerated despite this adolescent's severe
      cardiac and pulmonary illnesses. There was no evidence of increased neurotoxic
      symptoms in the presence of the ischemic brain damage. With its favorable side
      effect profile, risperidone may hold promise in the treatment of patients with
      psychotic disorders due to general medical conditions.

PMID- 9231300
TI  - Urinary catecholamine excretion and behavioral differences in ADHD and normal
      boys.
AB  - Urinary catecholamine excretion was assessed in 15 boys with attention
      deficit/hyperactivity disorder (ADHD) and 16 normal controls during a defined
      physical and mental task. Dihydroxyphenylalanine, dopamine, norepinephrine (NE),
      epinephrine (EPI), 3,4-dihydroxyphenylacetic acid, and 3,4-dihydroxyphenylglycol
      (DOPEG) concentrations were assayed by high-pressure liquid chromatography with
      electrochemical detection. The urinary concentration of DOPEG, an NE metabolite
      that has not been previously measured in ADHD, was significantly lower in the
      ADHD subjects than in the normal controls. There was also a trend for lower
      urinary EPI levels in the hyperactive boys. Stepwise multiple regression analyses
      demonstrated that DOPEG and EPI each contributed significantly to the variance in
      the behavioral symptoms within the full sample. The results are consistent with
      previous reports of abnormal metabolism of norepinephrine and epinephrine in
      ADHD. These neurochemical findings may be due to differences between ADHD and
      normal boys in neuronal (central or peripheral) or nonneuronal (e.g., adrenal,
      renal) activity. The results are also consistent with prior findings in normal
      children of an inverse relationship between EPI excretion and inattentive,
      restless behaviors. Together, these findings suggest caution in ascribing
      metabolite changes to ADHD or to ADHD-like behaviors that may be seen in normal
      children.

PMID- 9231302
TI  - Risperidone in young children with pervasive developmental disorders and other
      developmental disabilities.

PMID- 9231303
TI  - Severe weight loss induced by Adderall in a child with ADHD.

PMID- 9231304
TI  - Correlated changes in symptoms and neurotransmitter indices during maintenance
      treatment with clozapine or conventional neuroleptics in adolescents and young
      adults with schizophrenia.
AB  - A study of 40 young patients (age 14-22 years) with DSM-III-R schizophrenia
      (without substance abuse) was conducted following a mean of 3.4 years of
      neuroleptic treatment. After failing on conventional agents in clinical trials
      lasting a mean of 2 years, 20 patients were prospectively maintained on open
      label clozapine (mean 324 mg daily), and another 20 patients continued on typical
      neuroleptics (mean 465 mg chlorpromazine-equivalents daily). Patients were then
      sampled for biochemical measures and assessed for psychopathology (Brief
      Psychiatric Rating Scale, Scales for the Assessment of Positive/ Negative
      Symptoms) on six occasions at consecutive 6-week intervals-during maintenance
      treatment on clozapine or conventional neuroleptics. There were 22-fold
      interindividual differences in clozapine levels and also high intraindividual
      differences over time. Maintenance dosage was linearly related to plasma levels
      of clozapine and its metabolites. Prolactin levels were elevated with typical
      neuroleptics but not clozapine. Blood levels of serotonin,
      methoxyhydroxyphenylglycol (MHPG), norepinephrine, and epinephrine (but not
      dopamine) were significantly higher in clozapine-treated patients than in
      conventionally treated patients. Higher serotonin levels were associated with
      significantly fewer negative symptoms, whereas higher MHPG levels were correlated
      with less depression. These findings suggest involvement of norepinephrine and
      serotonin in the pathophysiology of schizophrenia (with depression associated
      with lower MHPG levels and negative symptoms associated with lower serotonin
      levels) and in the therapeutic actions of clozapine. Speculatively, a treatment
      strategy of targeting specific neurotransmitter systems might be based on the
      presence of specific symptoms in adolescents and young adults with schizophrenia.

PMID- 9231305
TI  - Erythromycin interaction with risperidone or clomipramine in an adolescent.
AB  - An adverse event is described which appeared when the macrolide antibiotic
      erythromycin was added to a regimen of risperidone 0.5 mg bid and clomipramine 50
      mg tid in a 15-year-old male being treated for Tourette's, obsessive-compulsive,
      and attention-deficit hyperactivity disorders. An acute onset of behavioral
      symptoms, including agitation, labile mood, incessant talking, and
      argumentativeness, began within 24 h of starting the erythromycin and persisted
      for 9 days after its discontinuation. It was followed by a return to stable
      functioning on the prior risperidone-clomipramine regimen. Erythromycin,
      risperidone, and clomipramine are all metabolized by the hepatic cytochrome P450
      system. It is postulated that the addition of erythromycin, a known inhibitor of
      CYP3A and CYP1A2, resulted in alterations in the metabolism of clomipramine and
      risperidone. Clomipramine metabolism is dependent upon the isoenzymes CYP2D6 and
      CYP1A2, and risperidone is a substrate for CYP2D6. Erythromycin would inhibit
      demethylation of clomipramine at the 1A2 isoenzyme and lead to a dual interaction
      between risperidone and clomipramine at the CYP2D6 isoenzyme. The subsequent
      increases in plasma levels of clomipramine, risperidone, their metabolites, or a
      combination of these agents could explain the adverse effects noted in this
      patient. In the absence of risperidone, clomipramine could have been
      metabolically cleared by CYP2D6. In the absence of clomipramine, risperidone
      clearance would not be affected by erythromycin. So the proposed mechanism
      requires an interaction involving all three agents: erythromycin, clomipramine,
      and risperidone. Alterations in plasma protein binding may also have played a
      role, because all three agents are extensively protein bound. Caution is urged
      when prescribing erythromycin with psychotropic drugs that are highly protein
      bound and/or are metabolized by the same P450 isoenzymes.

PMID- 9231306
TI  - Differential response of psychotic and obsessive symptoms to risperidone in an
      adolescent.
AB  - A 13-year-old boy with psychotic, depressive, and obsessive-compulsive symptoms
      initially presented with auditory and visual hallucinations and a lifetime of
      excessive worries about contamination. Family history was significant for
      schizophrenia and compulsive behavior. When treated with clomipramine 100 mg
      daily (plasma level 85 ng/mL), obsessive-compulsive symptoms but not the
      hallucinations improved significantly, and racing thoughts and grandiosity
      developed later. Haloperidol 0.5 mg daily reduced the psychotic symptoms but was
      poorly tolerated, and then trifluoperazine 3 mg daily was ineffective, so
      clomipramine was discontinued (without worsening of OCD symptoms).
      Trifluoperazine in combination with lithium 1500 mg daily (0.9 meq/L), and then
      with the addition of carbamazepine 250 mg daily (3.7 micrograms/mL), was only
      partially helpful. Dose reductions in any medication led to increased psychotic
      symptoms within days. Trifluoperazine was then replaced by risperidone 3 mg twice
      daily. Within 2 weeks of starting risperidone, psychotic symptoms ceased but the
      patient experienced an incapacitating exacerbation of obsessive-compulsive
      symptoms, experiencing the most severe symptoms in his illness. Sertraline 50 mg
      reduced the OCD symptoms only briefly. After 5 months on risperidone, risperidone
      and sertraline were discontinued, and the obsessive-compulsive symptoms
      significantly decreased within 2 weeks. These clinical observations suggest that
      even when risperidone has a therapeutic antipsychotic effect, it may exacerbate
      obsessive-compulsive symptoms in predisposed adolescents.

PMID- 9231308
TI  - Neuroleptic malignant syndrome: a psychopharmacogenetic perspective.

PMID- 9231307
TI  - Opportunities on the Internet for child and adolescent psychopharmacologists: net
      access and mailing lists.
AB  - The Internet, a system linking computers around the world, provides clinical and
      research psychopharmacologists with a convenient and efficient way to exchange
      information and offers a growing number of services to facilitate patient care.
      These opportunities are not theoretical, not in the future, and not for a select
      few. Many patients are already benefitting from practitioners who have sought
      guidance for their clinical work on the Internet. This article describes, for the
      novice user, how to begin the Internet journey. It also discusses
      psychopharmacology-related mailing lists, including a site that specializes in
      child and adolescent psychopharmacology. Subsequent articles will (1) show how to
      use Medlines to conduct literature searches and retrieve abstracts and articles
      from the computer screen, (2) describe ways to enter and traverse the World Wide
      Web (the "multimedia" portion of Internet), and (3) survey the use of "Web
      browsers" to find specialized psychopharmacology resources and databases,
      electronic journals, pertinent bulletin boards, and support services for patients
      and families-all with an emphasis on direct benefits to the practicing
      psychopharmacologist.

PMID- 9231309
TI  - The association between major depression and headache: results of a longitudinal
      epidemiologic study in youth.
AB  - Retrospective epidemiologic research in adults suggests that a long-term
      association between major depression and headache arises during childhood or
      adolescence. This study uses data from a prospective epidemiologic study to
      examine the association between major depression and headache from late childhood
      into early adulthood. An epidemiologically selected sample of 776 youth, aged 9
      18, was assessed psychiatrically in 1983 using DISC interviews with both youth
      and parent informants. Reassessments were conducted in 1985-1986 and 1992.
      Current and past histories of functionally impairing migraine or chronic headache
      were elicited in both 1985-1986 and 1992. Regression analyses examined the
      relationships between major depression and headache status. The prevalence of
      current functionally impairing headache was approximately 10% in both 1985-1986
      and 1992. There were lifetime and cross-sectional associations between headache
      and major depression. Headache was approximately twice as common in depressed
      adolescents compared with nondepressed adolescents. Major depression in
      adolescents, without current or past headache, prospectively predicted the new
      onset of headaches in young adulthood. Among adolescents who had no history of
      chronic impairing headache in 1985-1986, those with current major depression
      faced a nearly tenfold increased risk of developing such headaches at some time
      during the next 7 years. Consistent with findings of retrospective studies among
      adults, a longitudinal/ developmental relationship between major depression and
      functionally impairing headache was found in this prospective epidemiologic study
      of youth. These findings suggest that (1) neurochemical and pharmacologic
      commonalities between depression and headache should receive further
      investigation and that (2) it may be clinically useful to inquire about family
      history of headache syndromes in adolescents with major depression because such
      questioning may provide insight about the risk of subsequent functionally
      impairing headache in a depressed adolescent.

PMID- 9231310
TI  - Open-label treatment of comorbid depression and attentional disorders with co
      administration of serotonin reuptake inhibitors and psychostimulants in children,
      adolescents, and adults: a case series.
AB  - Attention-deficit hyperactivity disorder (ADHD) and major depression are common
      ailments that can cause significant dysfunction throughout the life cycle. These
      two disorders may occur comorbidly. This case series describes 7 pediatric
      patients (aged 10-16 years) and 4 adults (aged 38-44 years) whose ADHD and
      comorbid major depression were treated in a naturalistic open clinical fashion.
      For all 11 patients, symptoms of major depression appeared to respond well to
      either fluoxetine or sertraline monotherapy. Using starting doses of fluoxetine
      10 mg or sertraline 25 mg daily, we did not observe any adverse behavioral
      activation or clinical deterioration. However, no improvement in ADHD symptoms
      was observed in any patient during fluoxetine or sertraline monotherapy.
      Adjunctive treatment with a psychostimulant seemed necessary for chronic ADHD
      symptoms to be effectively addressed. The psychostimulants did not appear to
      provide observable antidepressant effects. With the exception of one adult who
      had a 20 mm Hg increase in diastolic pressure on methylphenidate monotherapy at
      22.5 mg daily, the administration and coadministration of these agents were not
      associated with significant changes in blood pressure or heart rate. No patient
      developed suicidality, increased aggressiveness, mania, or other problematic side
      effects. This combination therapy was well tolerated and appeared to be effective
      in ameliorating both ADHD and depressive symptoms. These cases support previous
      suggestions that adjunctive treatment with psychostimulants might be a safe and
      effective intervention for children treated with fluoxetine or sertraline who
      have persistent ADHD symptoms and suggests that such combined treatment may be
      suitable for adults as well.

PMID- 9231311
TI  - Use of risperidone in pervasive developmental disorders: a case series.
AB  - A series of 14 children and adolescents (ages 9-17 years, 10 males) were treated
      with risperidone for pervasive developmental disorder. The rationale for using an
      atypical neuroleptic agent is based on its ability to target both positive and
      negative symptoms of schizophrenia. It was postulated that symptoms similar to
      the positive and negative symptoms of schizophrenia may be observed in the
      pervasive developmental disorders and might respond favorably to risperidone.
      Twelve of the 14 youths had been treated previously with several psychotropic
      drugs, often concurrently. Risperidone was initiated at a starting dose of 0.25
      mg twice daily and increased in 0.25 mg/day increments every 5-7 days. Optimal
      dosages ranged from 0.75 to 1.5 mg daily in divided doses. Thirteen of the 14
      youths appeared to benefit from risperidone. Improvement in functionality on the
      Children's Global Assessment Scale was demonstrated in 13 of 14 cases. Disruptive
      behaviors, when present, markedly decreased on risperidone. Ten patients showed a
      marked reduction in agitation and anxiety. Social awareness improved markedly in
      10 patients, moderately in 3, and only slightly in 1. All but 1 patient
      demonstrated a lessening in obsessional behaviors. Effects on attention were
      uniformly positive. Side effects were minimal at the dosages used in this study;
      5 patients had initial sedation. Neither extrapyramidal side effects nor
      agitation was observed in any case. Ten of 14 youths could be managed with
      risperidone monotherapy. During the follow-up period (mean 7 months), none of the
      patients experienced a major relapse while taking risperidone. Positive and
      negative symptoms, as typically characterized in schizophrenia, were both found
      to improve equally well with risperidone treatment. Based on these findings, a
      prospective clinical trial with a randomized controlled design is warranted.

PMID- 9231312
TI  - Behavioral therapy in children and adolescents with obsessive-compulsive
      disorder: a pilot study.
AB  - Despite advances in pharmacotherapy for obsessive-compulsive disorder (OCD),
      medication treatments are not always effective. This pilot project examined the
      feasibility of a structured behavioral therapy program in the treatment of
      children and adolescents with OCD. Ten subjects with a primary diagnosis of OCD
      were invited to participate in the treatment program. Seven youngsters, 5 boys
      and 2 girls (age range 10.8-15.8, mean 13.0 years), participated and were treated
      for a mean of 14 sessions. These 7 subjects showed a broad range of OCD severity,
      as measured by the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS score
      range 12-29). Five subjects were also receiving antiobsessional medication (dose
      was not changed during the trial), and 2 subjects were treated without
      medication. All 7 youngsters showed a clinically significant reduction in the
      CYBOCS score at treatment endpoint (mean change 61%, range 30%-90%, effect size
      2.04, p < 0.05), and the therapeutic gains were stable for at least 3 months
      after treatment. One of 5 children who had been receiving concurrent
      antiobsessional medication was able to tolerate a dose reduction following
      behavioral treatment. Two to three booster sessions within 6 months posttreatment
      were effective in preventing relapse in 4 of 6 subjects. The 3 children who
      declined behavioral treatment showed no improvement at 3-month and 6-month follow
      up. Behavioral treatment appeared to be a useful adjunct to medication in
      children and adolescents with OCD. Further research could evaluate whether
      behavioral treatment would lower the dose requirements for children receiving
      antiobsessional medications. Randomized clinical trials are also needed to
      confirm the effectiveness of behavioral therapy alone or in combination with
      medication.

PMID- 9231313
TI  - A possible clonidine-trazodone-dextroamphetamine interaction in a 12-year-old
      boy.
AB  - A 12-year-old boy on a dextroamphetamine-clonidine-trazodone treatment regimen
      had a recurrence of insomnia, and his bedtime trazodone dose was doubled from 50
      mg to 100 mg. Within 45 mins after taking the first 100-mg trazodone dose on an
      empty stomach, the patient had a syncopal episode associated with hypotension,
      bradycardia, and sedation. The drug reaction could have resulted from either
      trazodone or clonidine, but it is more likely to have resulted from a
      pharmacodynamic clonidine-trazodone interaction, presumably aggravated by rapid
      absorption (on an empty stomach) of a recently increased dose of trazodone. It is
      conceivable but less likely that the psychostimulant was a clinically significant
      factor. However, a drug interaction between clonidine and D-amphetamine does not
      need to be postulated to explain this child's syncopal reaction. The authors
      advise that (1) if trazodone and clonidine are used concurrently, the doses of
      both agents should be changed slowly, (2) blood pressure and pulse should be
      carefully monitored at baseline and then periodically during treatment, and (3)
      administration of trazodone on an empty stomach, and especially dose increases on
      an empty stomach, should be avoided. Physicians should remain aware that
      trazodone has the potential to produce hypotension and sedation, especially when
      combined with other agents (such as clonidine) that might produce the same
      adverse effects.

PMID- 9231314
TI  - Erythromycin and clomipramine: noncompetitive inhibition of demethylation.

PMID- 9231315
TI  - Double-blind versus open evaluations of stimulant drug response in children with
      attention-deficit hyperactivity disorder.
AB  - Although placebo controls and double-blind conditions are considered to be
      essential for the unbiased scientific assessment of drug effects, there is very
      little research on these procedures in the pediatric psychopharmacology
      literature. To examine the impact of controlled assessment procedures on the
      magnitude of observed drug effects, two groups of children with attention-deficit
      hyperactivity disorder (ADHD) were evaluated for response to methylphenidate
      under two different assessment procedures. One group (n = 33) was part of a
      placebo-controlled, double-blind crossover research protocol, with randomized
      dose sequences, compliance checks, numerous dependent measures, written informed
      consent, and a considerable amount of staff involvement. The other group (n = 43)
      received pharmacotherapy at a community-based child psychiatry outpatient service
      where they were followed in a routine clinical manner, with "no treatment" as the
      only control condition, standard fixed-dose titration, parental responsibility
      for data collection, use of form letters, and minimal staff involvement. Each
      individual in both groups received divided doses of 0.3 and 0.5/0.6 mg/kg daily
      for a minimum of 1 week at each dose. Comparisons of teacher ratings obtained for
      the two assessment procedures revealed highly similar findings. The results of
      this study are discussed with regard to both their methodological and clinical
      implications.

PMID- 9231316
TI  - Methylphenidate slows right hemisphere processing in children with attention
      deficit/hyperactivity disorder.
AB  - To examine the effects and particularly, any potential detrimental effects of
      methylphenidate on right hemisphere processing in children with attention
      deficit/hyperactivity disorder (ADHD), the performance of 26 children (aged 8-15
      years) with ADHD was compared under methylphenidate and placebo on various
      cognitive tasks in a double-blind within-subjects design. Results indicated that
      reaction times on a tachistoscopic task were slower on methylphenidate for
      stimuli that produced a left visual field advantage (reflecting better right
      hemisphere functioning) but not for stimuli that produced a right visual field
      advantage (reflecting better left hemisphere functioning) or for bilateral
      stimuli. It is argued that methylphenidate induces a slower response on tasks
      involving right hemisphere processing, resulting in slower reaction times and
      unchanged accuracy rates. Findings on two tasks that more closely reflect
      classroom-type tasks revealed an improvement in performance on methylphenidate,
      suggesting that any stimulant-induced benefits on learning style may have
      overcome detrimental effects on unilateral processing. These findings may help
      understand the complex, diverse, and sometimes unpredictable effects of
      psychostimulants on cognitive functioning that are observed clinically in
      individuals treated for ADHD.

PMID- 9231317
TI  - An open trial of venlafaxine in the treatment of attention-deficit/hyperactivity
      disorder in children and adolescents.
AB  - A 5-week open trial of venlafaxine was conducted in 16 children and adolescents
      (mean age 11.6 years) with attention-deficit/hyperactivity disorder (ADHD) in
      order to estimate the appropriate dosage range and to determine the extent of
      side effects. Subjects were evaluated using a structured clinical interview and a
      computerized diagnostic assessment, and subjects diagnosed with ADHD and without
      comorbid depression were asked to enter the study. Conners Parent Rating Scale
      (CPRS) and Conners Continuous Performance Test (CPT) were performed at baseline
      and at the end of the 5-week trial. Two subjects were lost to follow-up. Of the
      remaining 14 patients, 7 subjects displayed a decrease of at least one standard
      deviation from their baseline on one of the CPRS subscale scores and had
      subjective reports from parents of improved behavior. There were no statistically
      significant effects of venlafaxine on reaction times or on the number of
      commission and omission errors on CPT. Three ADHD subjects displayed a worsening
      of their hyperactivity and required discontinuation of venlafaxine, and nausea
      led to drug discontinuation in 1 patient. The mean daily dose of venlafaxine was
      60 mg (1.4 mg/kg), administered 2-3 divided doses, there were no effects on blood
      pressure or heart rate. In this sample, low doses of venlafaxine appeared to be
      effective in reducing behavioral but not cognitive symptoms of ADHD in 7 of 16
      children and adolescents (44%), and adverse effects were not tolerable in 4 of 16
      patients (25%). These preliminary results suggest that venlafaxine may aggravate
      symptoms of hyperactivity, consistent with the behavioral activation reported
      with fluoxetine and sertraline in children.

PMID- 9231318
TI  - Risperidone in the treatment of children and adolescents with schizophrenia: a
      retrospective study.
AB  - Risperidone is a newly available atypical antipsychotic agent that has been
      reported to be associated with fewer extrapyramidal side effects (EPS) than
      conventional neuroleptics in adults with schizophrenia. This study assessed the
      safety and efficacy of risperidone in 16 children and adolescents (aged 9-20
      years, mean 14.9 years) who were clinically diagnosed with psychotic disorders:
      13 patients met DSM-III-R criteria for schizophrenia, 2 met criteria for
      schizoaffective disorder, and 1 had schizophreniform disorder. Eleven of the 16
      patients had previous unsuccessful neuroleptic trials. Patient charts were
      reviewed by the patients' child and adolescent psychiatrist for diagnoses,
      clinical changes, and adverse events. Clinical response was assessed
      retrospectively using the Brief Psychiatric Rating Scale (BPRS) and the Clinical
      Global Impression (CGI) scale. With the risperidone dose titrated gradually, an
      optimal clinical response was found at a mean daily risperidone dose of 5.93 mg
      (range 2-10 mg). All but one of the 16 patients had an adequate clinical response
      to risperidone therapy. Statistically significant improvements were found in the
      CGI (p < 0.0001), the BPRS Total Score (p < 0.0001), and the BPRS Negative
      Symptom Score (p < 0.001). In general, only mild drug-induced side effects were
      experienced, with 5 patients developing mild sedation and 3 developing EPS.
      Risperidone appeared to be safe and effective in ameliorating symptoms of
      schizophrenia in this age group. It is speculated that the gradual titration of
      risperidone was crucial in achieving a relatively low rate of EPS.

PMID- 9231319
TI  - Electroconvulsive treatment in adolescents with pharmacotherapy-refractory
      depression.
AB  - The effectiveness and safety of ECT in pharmacotherapy-refractory depression was
      examined in 11 hospitalized adolescents (ages 16.3 +/- 1.7 years, 10 females)
      with a primary DSM-III-R diagnosis of mood disorder, which had failed to respond
      to three or more adequate trials of antidepressant pharmacotherapy. After a
      thorough diagnostic evaluation, patients received a course of ECT involving 11.2
      +/- 2.0 (range 8-15) administrations. ECT was commenced with bilateral treatment
      in 2 adolescents and nondominant right electrode placement in 9 patients; 5 of
      the 9 patients were subsequently changed to bilateral treatment. All 11 patients
      improved to a clinically significant degree. Significant improvements were noted
      in scores on the Children Depression Rating Scale-Revised (CDSR-R) and the Global
      Assessment of Functioning Scale (GAF) (p < 0.05). Euthymia, defined as CDRS-R
      score < or = 40, was achieved by 64% (7/11) of patients. The Mini-Mental State
      Examination showed no significant decline in cognitive functioning.
      Neuropsychological testing completed in 5 subjects both before ECT and 1-5 days
      after the last treatment, indicated a significant decline in attention,
      concentration, and long-term memory search. Minor side effects, experienced
      within the first 12 hours of treatment, were headache (80% of patients) and
      nausea/vomiting (64%). The potentially serious complication of tardive seizure
      (after full recovery of consciousness) occurred in 1 adolescent. Prolonged
      seizures (> 2.5 minutes) were noted in 7 of the 11 patients (9.6% of the 135 ECT
      administrations). Pending further research on ECT in youth, it is recommended
      that ECT should only be administered to youth in hospital settings, that all
      regularly administered psychotropic medications (including antidepressants) be
      discontinued before ECT and restarted after the final administration of ECT, and
      that physicians be aware that 12 treatments are usually sufficient, but that 15
      treatments may occasionally be necessary for treating depressed adolescents. With
      the understanding that scientific evaluation of ECT in youth is lacking, it
      appears that ECT can be an effective and relatively safe treatment for depressed
      adolescents who have failed to respond to antidepressant pharmacotherapy.

PMID- 9231320
TI  - Open trial lamotrigine in the treatment of self-injurious behavior in an
      adolescent with profound mental retardation.
AB  - This single case reports an open trial of lamotrigine in the treatment of self
      injurious behavior (SIB) and epilepsy in an 18-year-old female diagnosed with
      generalized seizure disorder, stereotypic movement disorder, and compulsive SIB
      in the context of profound mental retardation. Animal models of SIB suggest that
      the glutamate neurotransmitter systems, involved in the generation of epileptic
      seizures, may also have a role in the pathophysiology of SIB. Data suggesting
      that lamotrigine may decrease glutamate release encouraged an empirical trial of
      lamotrigine for treatment of SIB. After 4 weeks of treatment of lamotrigine 200
      mg daily, decreases in agitation and fearfulness were clinically observed, along
      with a 50% reduction in the frequency of SIB as measured by standardized scales.
      Good seizure control was maintained throughout the trial. No significant adverse
      effects were observed. Positive effects persisted at 1-year follow-up. Symptoms
      of stereotypic movement disorder appeared unchanged. Because these findings are
      preliminary, no clinical recommendations for the treatment of SIB with
      lamotrigine can be made until controlled studies have been completed.

PMID- 9231321
TI  - Sertraline-induced behavioral activation during the treatment of an adolescent
      with major depression.
AB  - Symptoms of behavioral activation in children and adolescents have been reported
      as possible adverse effects of treatment with fluoxetine and sertraline. A 15
      year-old with a single major depressive episode, dissociative periods, and
      anxious hyperventilation attacks was started on sertraline 50 mg (1 mg/kg) daily
      and, within 4 days, raised to 100 mg daily. All major symptoms resolved by 4
      weeks with no apparent side effects or adverse behavioral changes. Ratings of
      Global Assessment of Functioning and Clinical Global Impression Severity of
      Illness ratings reflected marked clinical improvement. The adolescent remained
      euthymic for 6 months but then experienced a return of some depressive symptoms.
      Within 3 days of raising the dose to 150 mg daily, the patient began to exhibit
      difficulty in falling asleep, hypermotoric behavior, and hypertalkativeness (in
      association with tremor and blurred vision). This episode was not of sufficient
      duration and did not fulfill a sufficient number of DSM-IV criteria to qualify as
      hypomania. The symptoms of behavioral activation lasted for 3 days and
      disappeared when sertraline was discontinued, but depressive and hyperventilation
      symptoms returned quickly. Reinstatement of 100 mg produced enduring recovery
      without the adverse effects. This case appears to suggest that rapid dose
      elevation may not be as important as dose quantity in eliciting adverse
      behavioral effects from sertraline. Judging from the few cases now in the medical
      literature, it appears that sertraline-induced behavioral activation may emerge
      at doses that vary considerably among individual youths (25-200 mg daily). In
      short, this drug-induced behavioral activation appears to be dose-dependent, but
      dose threshold varies widely among patients.

PMID- 9231322
TI  - The importance of the peptide bond at position 2 in HCO-Met-Leu-Phe-OMe analogues
      as shown by studies on human neutrophils.
AB  - The formylpeptides formyl-methionyl-N-methylleucyl-phenylalanine methyl ester
      [for-Met-(NMe)Leu-Phe-OMe] 1, formyl-methionyl-2-aminotetralin-2-carboxyl
      phenylalanine methyl ester [for-Met-Atc-Phe-OMe] 2, formyl-methionyl-1,2,3,4
      tetrahydroisoquinoline-3-carboxyl-phenylalanine methyl ester [for-Met-Tic-Phe
      OMe] 3 and formyl-methionyl-2-aminoxy-4-methylvaleryl-phenylalanine methyl ester
      [for-Met-OLeu-Phe-OMe] 4 were synthesized in order to investigate the role of the
      amide bond at position 2 on biological activities on human neutrophils. Only
      analogue 2, which keeps the NH group at position 2, was found to retain activity
      though sterically encumbered.

PMID- 9231323
TI  - Structural polymorphism of gramicidin A channels: ion conductivity and spectral
      studies.
AB  - The relation between the various spatial structures of the gramicidin A channels
      and their ionic conductance has been studied. For this aim, various conformations
      of the peptide were pre-formed in liposomal bilayer and after subsequent fusion
      of liposomes with planar lipid bilayer the measured channel conductance was
      correlated with gramicidin structures established in liposomes. To form the
      single-stranded pi 6.3 pi 6.3 helix the peptide and lipid were co-dissolved in
      TFE prior to liposome preparation. THF and other solvents were used to form
      parallel and antiparallel double helices. Conformation of gramicidin in liposomes
      made by various phosphatidylcholines was monitored by CD spectroscopy, and
      computer analysis of the spectra obtained was performed. After fusion of
      gramicidin containing liposomes with planar bilayer membranes from asolectin, the
      histograms of single-channel conductance were obtained. The histograms had one or
      three distinct peaks depending on the liposome preparation. Assignment of the
      structure of the channel to conductance levels was made by correlation of CD data
      with conductance histograms. The channel-forming analogue, des(Trp-Leu)2
      gramicidin A, has been studied by the same protocol. The channel conductances of
      gramicidin A and the shortened analogue increase in the following order:
      antiparallel < parallel < pi 6.3 pi 6.3. Single-channels formed by double helices
      have higher dispersity of conductance than the pi 6.3 pi 6.3 helical channel.
      Lifetimes of the double helical and the pi 6.3 pi 6.3 helical channels are very
      close to each other. The data obtained were compared with theoretically predicted
      properties of double helices [1].

PMID- 9231324
TI  - Synthesis of fragments of the peptide component of pseudobactin.
AB  - Pseudobactin is a structurally complex and physiologically important siderophore
      (microbial iron chelator] from Pseudomonas putida-fluorescens. Various fragments
      of the unusual peptide component of pseudobactin listed below were prepared by
      solution-phase peptide synthesis. L-Lys.D-threo-beta-OH Asp.L-Ala.D-allo-Thr.L
      Ala L-Lys.D-threo-beta OH Asp.L-Ala.D-allo-Thr D-threo-beta-OH Asp.L-Ala.D-allo
      Thr.L-Ala.D-N-OH-cycloOrn D-threo-beta-OH-Asp.L-Ala.D-allo-Thr.L-Ala L-Ala.D-allo
      Thr.L-Ala.D-N-OH-cycloOrn A class of related peptides named pseudomycins have
      shown promising antifungal activity. To examine if these peptide fragments above
      would elicit similar activity, the fragments were tested and found to have no
      antifungal activity in limited bioassays.

PMID- 9231326
TI  - Conformational analysis of neuropeptide Y segments by CD, NMR spectroscopy and
      restrained molecular dynamics.
AB  - Neuropeptide Y (NPY), a peptide amide comprising 36 residue has been shown to act
      as a potent vasoconstrictor. In order to shed light on the structural
      requirements for the biological activities with respect to the different
      prerequisites for affinity to the NPY receptor subtypes Y1 and Y2, in the present
      study the syntheses and conformational analyses of two C-terminal segments,
      NPY(18-36) and NPY(13-36), are described. The results obtained by CD
      measurements, two-dimensional NMR spectroscopy and a conformational refinement of
      the NMR-derived structure by molecular mechanics stimulations support the
      findings of previously published structure-activity relationship studies for
      biologically active and selective compounds. In particular, the alpha-helical
      conformation as well as an appropriate exposure of the side chains of the
      critical C-terminal dipeptide within NPY(18-36) are in agreement with the
      prerequisites proposed for Y2 receptor binding of that segment.

PMID- 9231325
TI  - A combinatorial peptide library around variation of the human immunodeficiency
      virus (HIV-1) V3 domain leads to distinct T helper cell responses.
AB  - The hypervariable domain of the HIV gp120, the V3 loop domain, represents a
      target for neutralizing antibodies and for HIV vaccine strategies. In this study,
      we have investigated in murine species the potential cross-reactivity of immune
      responses elicited by immunization either with individual V3 peptides, derived
      from distinct HIV sequences (BRU, RF, SF2, MN and ELI sequences), or with a V3
      combinatorial peptide library. We observed that individual V3 peptides are
      immunogenic but elicit a specific B- and T-cell immune response that is mainly
      restricted to the sequence of the immunizing peptide. In particular, T-cell
      responses that depend on T-cell receptor recognition of peptides bound to the
      molecules encoded by the major histocompatibility complex were significantly
      influenced by small differences in the peptide amino acid sequence. The
      combinatorial V3 peptide library, previously described as B- and T-cell
      immunogens, induced a more broadly reactive immune response, specially when T
      cell cytokine secretion was used as a readout for restimulation of T-cells with
      individual V3 peptides. These data suggest that amino acid variations in the
      sequence of an antigenic peptide could lead to the induction of different
      transducing signals in the primed T-cell population and to the activation of T
      cells with distinct cytokine secretion properties. These observations may have
      implications in the understanding of antigenic variability and in the design of
      vaccine strategies.

PMID- 9231327
TI  - Current concepts in intestinal peptide absorption.
AB  - Today there is considerable interest in oral peptide delivery. However, oral
      administration of peptides is limited by a low bioavailability and a high
      variability in plasma levels. A review is given of the literature describing the
      major barriers in peptide absorption, the basic mechanisms of intestinal peptide
      transport, the experimental models and the pharmaceutical approaches currently
      used in the investigation of peptide and protein absorption processes.

PMID- 9231328
TI  - Multiple column synthesis of a library of T-cell stimulating Tn-antigenic
      glycopeptide analogues for the molecular characterization of T-cell-glycan
      specificity.
AB  - A series of peptides and glycopeptides derived by amino acid and glycosyl amino
      acid scans through the self peptide from CBA/J mouse haemoglobin Hb (67-76).
      VITAFNEGLK, was synthesized by multiple column peptide synthesis (MCPS).
      Investigation of glycopeptide binding to the mouse major histocompatibility class
      II molecule Ek showed that glycans in position 72 did not interfere with the
      binding to Ek. Immunization experiments revealed that glycopeptides with the
      glycan in position 72 were immunogenic. Therefore a series of N-linked and O
      linked glycopeptides with the glycan attached in the position 72 either to
      serine, threonine or asparagine was synthesized by MCPS. The glycan structure was
      furthermore varied with respect to monosaccharide component, size of
      oligosaccharide, anomer configuration and stereochemistry of essential hydroxyl
      groups in order to investigate the specificity of the interaction with the T-cell
      receptor. Easy synthesis of ready to use Ser and Thr building blocks
      corresponding to mucin core 1, the Tn-antigen and its beta-anomer were developed
      using trichloroacetimidates as glycosyl donors and reduction with in situ
      acetylation of the azide containing glycosylation products. Synthesis of an alpha
      linked GlcNAc-Thr building block was achieved by glycosylation of Fmoc-Thr-OPip
      with 2-azido-2-deoxy-3,4,6-tri-O-acetyl-D-glycopyranosyl trichloroacetimidate as
      a glycosyl donor. Other building blocks were obtained by previously described
      procedures.

PMID- 9231329
TI  - Hydrophobic effects on antibacterial and channel-forming properties of cecropin A
      melittin hybrids.
AB  - The design of cecropin-melittin hybrid analogues is of interest due to the
      similarities in the structure of the antimicrobial peptides cecropin and melittin
      but differences in their lytic properties. We suspected that a hydrophobic
      residue in position 2 of milittin (Ile8 in the hybrid) plays an important role in
      the activity of the 15-residue hybrid, KWKLFKKIGAVLKVL-NH2, [CA(1-7)M(2-9)NH2]
      and have now examined its role in the analogue toward five test bacteria.
      Deletion of Ile8 reduced activity, and it was not restored by lengthening to 15
      residues by addition of another threonine at the C-terminus. Replacement of Ile8
      by a hydrophobic leucine maintained good activity and Ala8 was equally active for
      four organisms, although less active against Staphylococcus aureus. Replacement
      by the hydrophilic Ser8 strongly reduced potency against all five organisms.
      Deletion of Leu15 decreased activity, but addition of Thr16 maintained good
      activity. The presence of hydrophobic residues appears to have a significant
      effect on the process of antibacterial activity. These peptide analogues showed
      voltage-dependent conductance changes and are capable of forming ion-pores in
      planar lipid bilayers. The antibacterial action of the peptides is thought to be
      first an ionic interaction with the anionic phosphate groups of the membrane
      followed by interaction with the hydrocarbon core of the membrane and subsequent
      reorientation into amphipathic alpha-helical peptides that form pores (ion
      channels), which span the membrane. The analogue also showed an increase in alpha
      helicity with an increase in hexafluoro 2-propanol concentration.

PMID- 9231330
TI  - The use of proton chemical shifts to define the solution structure of a dimeric
      peptide.
AB  - For flexible peptides, nuclear Overhauser Effects (NOE) experiments do not
      provide enough information to ensure a correct definition of their solution
      structure. The use of distance constraints, derived from the knowledge of proton
      chemical shifts, is developed to restrict the number of possible conformations.
      In the case of flexible molecules, randomization appears as an important factor
      of the correct estimation of the chemical shifts from the 3D structure. The
      refinement of the solution structure of the highly flexible AVP-like parallel
      dimer is described to illustrate this process.

PMID- 9231331
TI  - Inclusion volume solid-phase synthesis.
AB  - Solid-phase synthesis of peptides was carried out using only the volume of the
      solvent included in the swollen solid-phase resin heads (inclusion volume
      synthesis). This approach enables (i) the use of higher concentrations of
      activated amino acids, resulting in increased coupling rates, (ii) drastically
      decreased consumption of solvents, and (iii) the construction of multiple peptide
      synthesizers having virtually no reaction vessels.

PMID- 9231332
TI  - Multivalent ligand system carrying enkephalin and neurotensin coimmobilized on
      liposomes.
AB  - A multivalent ligand system was constructed by coimmobilization of two kinds of
      peptide ligands, enkephalin and neurotensin derivatives having a dioctadecyl
      group, on dimyristoylphosphatidylcholine (DMPC) liposomes. The enkephalin
      derivatives are Tyr-D-Ala-Gly-Trp-Leu-(Sar-Sar-Pro)n-[N(C18H37)2] (Enk3nD, n = 0,
      1, 2), where a dioctadecyl group was connected to the C-terminal side of
      enkephalin directly or through a hydrophilic and flexible spacer chain of
      different lengths. The neurotensin derivatives are Ac-Glu[N(C18H37)2l-(Sar-Sar
      Pro)n-Arg-Arg-Pro-Tyr-Ile-Leu-OH (D3nNT, n = 0, 1, 2, 3). The derivatives were
      spontaneously immobilized on DMPC liposomes by overnight incubation. The receptor
      affinity of the enkephalin derivatives became significantly higher upon
      immobilization on liposomes. The highest affinity was obtained for the delta
      receptor by Enk6D immobilized on DMPC liposomes. This affinity is higher than
      that of enkephalinamide. Neurotensin derivatives coimmobilized with large amounts
      of Enk3D on the DMPC liposomes show higher affinity than the neurotensin
      derivatives immobilized alone. The effect of Enk3D on the receptor affinity of
      the coimmobilized neurotensin derivative disappeared by the addition of [Ala2,
      MePhe4, Glyol5]enkephalin (DAGO). Therefore, the receptor affinity of a peptide
      hormone is altered by immobilization on DMPC liposomes and by coimmobilization
      with other peptide hormones. It was confirmed by fluorescent microscopy that the
      multivalent ligand system binds to receptors without release of the bound ligands
      from DMPC liposomes.

PMID- 9231333
TI  - Immunogenicity studies with haptenated melittin peptides: implication for
      membrane involvement during the recognition step.
AB  - Melittin peptides carrying 2,4-dinitro-6-carboxyphenyl (Dncp) haptenic groups
      regularly evoked anti-hapten IgG responses in mice or guinea pigs when the hapten
      was C-terminally attached. Single haptens on the N-terminal helix in several
      positions gave poor or no responses in the early stages but adequate titres after
      prolonged immunization. Peptides with Dncp at the C-terminus as an invariant
      feature and a second Dncp in various positions along the peptide chain did not
      fail to produce adequate responses. The hampering effect is not due to a defect
      at the T-cell level but involves the recognition step on the B-cell. It is
      implied that the haptenic interaction with the paratope of the recognizing
      immunoglobulin on the B-cell involves the cell membrane in an important way. It
      is also suggested that late antibody responses should not be overlooked during
      the development of proteinaceous immunogens for vaccination.

PMID- 9231335
TI  - Cysteine racemization in peptide synthesis: a new and easy detection method.
AB  - A new method has been developed for the rapid determination of D-cysteine
      contents in synthetic peptides. It is based on the reduction of cystine residues,
      when present, with tris-alkylphosphines, selective derivatization of the cysteine
      residues with 4-vinylpyridine, followed by acid hydrolysis of the (4
      pyridylethyl)cysteine-peptides. Baseline enantiomeric resolution of the D,L-S
      beta-(4-pyridylethyl)cysteine, and thus quantification of D-enantiomer contents
      at levels < or = 1%, is easily achieved by capillary zone electrophoresis
      exploiting the host-guest complexation principle with crown ethers or by gas
      chromatography on chiral glass capillary columns upon conventional derivatization
      of the hydrolysate. The acid-stability of the (4-pyridylethyl)cysteine derivative
      prevents racemization via thiazoline intermediates and allows for standardization
      of the acid hydrolysis-dependent racemization.

PMID- 9231334
TI  - Backbone cyclization of the C-terminal part of substance P. Part 1: The important
      role of the sulphur in position 11.
AB  - Novel backbone-to-side chain and backbone-to-backbone cyclic analogues of
      substance P (SP) were prepared by solid-phase synthesis and screened for
      biological activity. An analogue containing a thioetherlactam ring between
      positions 9 and 11 showed an EC50 value of 20 nM toward the neurokinin 1 (NK-1)
      and was inactive toward the NK-2 and NK-3 receptors. On the other hand, in a
      multiple backbone cyclic peptide library of similar analogues, in which the
      sulphur was excluded from the ring, very low activity was detected. The activity
      was re-evaluated and was found to be even lower (EC50 = 0.11 mM) than the
      previously published data. These results indicate that the thioether moiety has a
      crucial role in receptor activation. The results also show tolerance of the NK-1
      receptor, but not NK-2 or NK-3, to cyclization of the C-terminal portion of the
      SP6-11 hexapeptide.

PMID- 9231336
TI  - Release characteristics of implantable cylindrical polyethylene matrices.
AB  - The geometrical relationship between a hemisphere and a cylinder has been
      investigated for controlled-release systems. The relationship was tested by
      comparing dissolution results with results from mathematical calculation based on
      the principles of diffusion for matrix systems. A procedure has been developed
      for producing implantable, cylindrical, low-density polyethylene matrices,
      uncoated or coated with a thin impermeable film and a thick paraffin layer except
      for a hole on the flat faces of the cylinder. Drug matrices were prepared from a
      blend of sodium salicylate and polymer compressed in an appropriately designed
      stainless-steel mould at 150 degrees C. Differential scanning calorimetry
      revealed that no decomposition product was formed in the matrix. When the surface
      area and the number of holes is increased, drug release also increases. When
      density is increased, however, drug release decreases significantly. Zero-order
      drug release was obtained from high-density covered one-hole and two-hole
      matrices. The diffusion coefficient was calculated as 0.067 day-1. The study
      suggested that true zero-order drug release could be obtained by drug diffusion
      from a hole, rather than from geometric shapes in the matrix systems. In
      addition, for constant release the diffusion area has to increase by
      approximately 25 mm2 every day, compared to the area of the previous day, because
      the diffusion distance increases logarithmically.

PMID- 9231337
TI  - Influence of moderate haemodilution with fluosol or normal saline on carbaryl
      disposition in Sprague-Dawley rats.
AB  - In rats carbaryl undergoes extensive biotransformation involving both albumin
      mediated hydrolysis and cytochrome P-450-mediated metabolism; studies have
      suggested that approximately one-half of a carbaryl dose is hydrolysed and one
      half is metabolized. Fluosol is known to be an inducer of cytochrome P-450, and
      Fluosol haemodilution reduces plasma albumin concentrations. The disposition of
      carbaryl was, therefore, determined in rats for 72 h after 40 mL kg-1
      haemodilution with Fluosol or normal saline (0.9% NaCl). Volumes of distribution
      were significantly reduced after saline haemodilution for 72 h but only at 48 h
      after Fluosol haemodilution. Fluosol and saline haemodilution had little
      influence on carbaryl total body clearance (CL). These results indicate that both
      hepatic and non-hepatic clearance pathways were not influenced by the
      haemodiluents or the haemodilution procedure.

PMID- 9231338
TI  - In-vitro permeability of the human nail and of a keratin membrane from bovine
      hooves: penetration of chloramphenicol from lipophilic vehicles and a nail
      lacquer.
AB  - Lipophilic vehicles and especially nail lacquers are more appropriate for topical
      application on the nail than aqueous systems because of their better adhesion.
      This work has, therefore, studied the penetration through the human nail plate of
      the model compound chloramphenicol from the lipophilic vehicles medium chain
      triglycerides and n-octanol and from a lacquer based on quaternary poly(methyl
      methacrylates) (Eudragit RL). The results were compared with data obtained with a
      keratin membrane from bovine hooves. If the swelling of the nail plate or the
      hoof membrane is not altered by use of lipophilic vehicles, the maximum flux of
      the drug is independent of its solubility in the vehicle and is the same as that
      from a saturated aqueous solution. These vehicles are not able to enter the
      hydrophilic keratin membrane because of their non-polar character and so cannot
      change the solubility of the penetrating substance in the barrier. If the
      concentration of the drug in the nail lacquer is sufficiently high, the maximum
      flux through both barriers equals that from aqueous vehicles or even exceeds it
      because of the formation of a supersaturated system. Penetration through the nail
      plate follows first order kinetics after a lag-time of 400 h. The course of
      penetration through the hoof membrane is initially membrane-controlled and later
      becomes a matrix-controlled process because of the membrane's greater
      permeability. Chloramphenicol is dissolved in the lacquer up to a concentration
      of 31%. The relative release rates from these solution matrices are independent
      of the drug concentration but they decrease on changing to a suspension matrix.
      These results show that drug flux is independent of the character of the vehicle
      and that penetration of the drug is initially membrane-controlled and changes to
      being matrix-controlled as the drug content of the lacquer decreases.

PMID- 9231339
TI  - Synthesis of 3-amino-2-(3-indolyl)propanol and propanoate derivatives and
      preliminary cardiovascular evaluation in rats.
AB  - A series of tryptamine analogues has been prepared and tested for their 5-HT1
      receptor agonist properties. The incorporation of an alkoxy group at the C-5
      position of the indole nucleus resulted in a short-lived and dose-dependent
      immediate antihypertensive and bradycardic response in anaesthetized
      spontaneously hypertensive rats (SHR). In addition, a carbomethoxy function at
      the beta-position of the side-chain of the tryptamines significantly increased
      the mean resting arterial blood pressure (MAP) in pithed rats and also produced
      contraction of the canine basilar artery in a dose-dependent fashion. Structure
      activity relationships (SAR) suggest that the 5-alkoxy group is an important
      pharmacophore in the production of the antihypertensive effect and that the
      introduction of a hydroxymethylene group on the side-chain, instead of the
      carbomethoxy group, changed the receptor affinity profile.

PMID- 9231340
TI  - The role of mammalian intestinal bacteria in the reductive metabolism of
      zonisamide.
AB  - Zonisamide (1,2-benzisoxazole-3-methanesulphonamide), a new anticonvulsant, is
      mainly metabolized to 2-sulphamoylacetylphenol by reduction of the benzisoxazole
      ring. Recent studies have shown that mammalian liver enzymes are responsible for
      the reduction of zonisamide. Because intestinal bacteria can also mediate the
      reduction of xenobiotics, this study was designed to evaluate the role of
      intestinal bacteria in in-vivo reductive metabolism of zonisamide. Treatment of
      rats with antibiotics significantly reduced the urinary and faecal excretion of 2
      sulphamoylacetylphenol after oral administration of zonisamide. Re-contamination
      of the antibiotic-treated rats with microflora restored the excretion of the
      metabolite. The caecal contents of the control rats had significant zonisamide
      reductase activity, whereas little or no zonisamide reductase activity was
      observed with the caecal contents of the antibiotic-treated rats. Eight pure
      strains of intestinal bacteria were tested for zonisamide reductase activity and
      the highest was observed in Clostridium sporogenes. We concluded that intestinal
      bacteria play a major role in the reductive metabolism of zonisamide to 2
      sulphamoylacetylphenol in-vivo.

PMID- 9231341
TI  - Stereoselective N-demethylation of chlorpheniramine by rat-liver microsomes and
      the involvement of cytochrome P450 isozymes.
AB  - Previous studies have suggested that degradation of the two stereoisomers of
      chlorpheniramine in the liver might be catalysed by different types of cytochrome
      P450. Stereoselective N-demethylation of chlorpheniramine and the involvement of
      cytochrome P450 (CYP) isozymes have, therefore, been investigated in the liver
      microsomes of eight-week-old male rats. Incubation of racemic chlorpheniramine
      with liver microsomes from the male rat resulted in the formation of both
      enantiomers of monodesmethylchlorpheniramine (DMChp). Further metabolism of DMChp
      to didesmethylchlorpheniramine (DDMChp) did not, however, occur. The S/R
      enantiomeric ratio for intrinsic clearance (Vmax/Km) was approximately 2.0,
      suggesting that the N-demethylation was stereoselective for S-(+)
      chlorpheniramine. On the other hand, although the Vmax/Km value for the formation
      of S-(+)- and R-(-)-DMChp increased with phenobarbitone-inducible rat-liver
      microsomes, there was no difference between the rates of N-demethylation of the
      enantiomers. In contrast, 3-methylcholanthrene reduced the intrinsic clearance of
      S-(+)-chlorpheniramine by N-demethylation and increased its value for R-(-)
      chlorpheniramine, showing no stereoselectivity for the N-demethylation of
      chlorpheniramine. The difference between the intrinsic clearance of the two
      enantiomers by N-demethylation was because of differences in affinity for the
      catalysing enzyme. This is indicative of stereoselective involvement of the main
      enzyme concerned in the N-demethylation of the enantiomers, considered to be CYP
      2C11. Anti-CYP 2C11 also partially inhibited the N-demethylation of racemic
      chlorpheniramine in rat-liver microsomes exposed to phenobarbitone and 3
      methylcholanthrene. That CYP 2B1 was involved in the N-demethylation of both
      enantiomers was also supported by results from an experiment using phenobarbitone
      inducible rat-liver microsomes. CYP1A1 did not, however, catalyse the N
      demethylation of either enantiomer. These results indicate that N-demethylation
      of the S-(+)-enantiomer of chlorpheniramine occurs preferentially in the
      microsomes, demonstrating the stereoselective contribution of CYP2C11.
      Immunoinhibition studies suggest, moreover, that the N-demethylation of both
      chlorpheniramine enantiomers is catalysed by CYP2B1, but not by CYP1A1.

PMID- 9231342
TI  - Optimization of the chiral inversion of 2-phenylpropionic acid by Verticillium
      lecanii.
AB  - Previous studies have demonstrated that Verticillium lecanii might be used as a
      microbial model of the inversion of 2-arylpropionic acids in man. This paper
      describes the optimization of the inversion process in respect of culture medium,
      pH, cell density and substrate concentration. The study demonstrates that optimum
      inversion occurs in Sorensen's phosphate buffer at pH 5.5. The extent and rate of
      inversion were also shown to be dependent on substrate concentration and cell
      density. This study will form the basis of the development of a microbial model
      of the metabolism of 2-arylpropionic acids which might be suitable for the in
      vitro screening of new compounds in this class.

PMID- 9231343
TI  - In-vitro binding of propiverine hydrochloride and some of its metabolites to
      serum albumin in man.
AB  - The distribution and pharmacological action of propiverine, a bladder spasmolytic
      agent, are affected by the extent of plasma-protein binding. Because attempts to
      assess the albumin-binding of propiverine have produced conflicting results, the
      binding parameters of the drug and some of its metabolites to serum albumin in
      man have been re-evaluated. In man propiverine is bound to serum albumin at a
      single site with high affinity (KA1 = 1.45 x 10(4) L mol-1) and at least two
      sites with low affinity (KA2 = 2.5 x 10(2) L mol-1). The metabolites of
      propiverine, namely M2 (dealkylated propiverine), M5 (the N-oxide of propiverine)
      and M6 (the N-oxide of M2), are less firmly bound to serum albumin; this is
      considered to be non-specific binding. Binding experiments with human serum
      revealed that there are additional binding proteins. At therapeutic plasma levels
      the extent of binding was calculated to be 90, 15, 60, and 20% for propiverine
      and the metabolites M2, M5, and M6, respectively. The strong binding of
      propiverine to serum proteins controls its availability to the liver. Because the
      metabolites are not tightly bound to serum proteins, after metabolism of
      propiverine its metabolites are easily eliminated.

PMID- 9231344
TI  - Fluorimetric determination of tissue distribution and differences between the
      activity of aspirin esterases I and II in mice and rats.
AB  - A modification of available fluorimetric methods, based on the native
      fluorescence of salicylic acid, has been used to assay the activity of aspirin
      esterases I and II in small amounts of several tissues from rats and mice. The
      results obtained showed that aspirin esterase I from mouse liver and kidney had
      the lowest activity and that the activity of aspirin esterase II from these
      organs was greater than that from the same organs from rats. Liver enzyme
      kinetics and tissue distribution in rats was shown to be similar to previous data
      obtained using a spectrophotometric method. This fluorimetric method, which is
      more sensitive and rapid than the spectrophotometric method, may be useful in
      studies on aspirin metabolism.

PMID- 9231345
TI  - Pharmacokinetics of heterologous and homologous immunoglobulin G, F(ab')2 and Fab
      after intravenous administration in the rat.
AB  - Because few pharmacokinetic studies of antibodies and their fragments have
      compared the influence of species origin and antibody size, the plasma
      pharmacokinetics of a single intravenous dose (0.7 mg kg-1) of 125I-labelled
      mouse, rat and human immunoglobulin G (IgG), and mouse F(ab')2 and Fab were
      investigated in the rat. IgG reached equilibrium after six distribution half
      lives, i.e. only 36-50 h post-dosing, and the distribution volume was about four
      times the rat plasma volume. IgG elimination half-lives ranged from 5.33 to 8.10
      days. Fragmentation of IgG into smaller fragments, F(ab')2 and Fab, resulted in
      pharmacokinetics that were molecular-weight-dependent with volume of distribution
      and systemic clearance values inversely related to antibody size. We conclude
      that antibody variability in terms of species origin and size influences antibody
      pharmacokinetics and should be carefully studied before selection of the best
      antibody for a clinical application.

PMID- 9231346
TI  - Pharmacokinetics and kinetic-dynamic modelling of aminophenones as methaemoglobin
      formers.
AB  - Methaemoglobin, the oxidized form of haemoglobin, can be formed by a variety of
      agents, most of which act to oxidize haemoglobin directly or indirectly. Cyanide
      has a higher affinity for methaemoglobin than for mitochondrial cytochromes,
      making methaemoglobin formation a basis for the treatment of cyanide poisoning.
      We used the beagle dog model to investigate the relationship between drug
      concentration and methaemoglobin levels for two candidate anti-cyanide compounds.
      The compounds studied were the aminophenones p-aminopropiophenone (PAPP) and p
      aminoheptylphenone (PAHP). Both PAPP and PAHP were given as intravenous boluses
      and as two different oral formulations. The kinetics of both compounds appeared
      to follow a three-compartment open model for intravenous bolus administration and
      a two-compartment open model for oral administration. The first distribution
      phase seen with the intravenous administration was obscured by the absorption
      phase during oral administration. Bioavailability for all formulations varied
      between 20 and 47%. For both compounds there was a delay between the appearance
      of drug in the plasma and the appearance of methaemoglobin (counter-clockwise
      hysteresis) which is suggestive of an active metabolite causing methaemoglobin
      formation. The pharmacodynamics were fit with an effect-compartment kinetic
      dynamic model linked to a sigmoid Emax pharmacodynamic model. Maximum amounts of
      methaemoglobin occurred between 2 and 4 h for PAHP and between 1 and 3 h for
      PAPP. When administered intravenously estimates of EC50 were lower than the
      estimates of EC50 from oral administration for both compounds. This might be
      because of oral first-pass inactivation or a 'first-pass' activation through the
      lungs contributing to the formation of an active metabolite. The phenones as a
      class appear to have the drug cleared and methaemoglobin return to near baseline
      within 12 h. Both compounds seem to produce sufficient methaemoglobin to treat
      acute cyanide poisoning and to serve as prophylactic agents against acute cyanide
      poisoning in a military setting.

PMID- 9231347
TI  - Saturable urinary excretion kinetics of famotidine in the dog.
AB  - An important elimination route of the histamine H2 antagonist famotidine is
      active tubular secretion via the renal organic cation transport system. To
      characterize the excretion kinetics of famotidine in-vivo, the relationship
      between plasma concentration and urinary excretion rate was investigated in the
      beagle dog over a wide concentration range. The maximum transport capacity and
      the apparent Michaelis-Menten constant of tubular secretion were estimated.
      Concentration-dependent renal clearance was determined either after intravenous
      infusion of high doses of famotidine for a short time or during continuous
      infusion. From individual experiments only indications of saturation were
      observed; these could not be quantified. A tubular titration curve, in which the
      active tubular famotidine secretion was plotted against the plasma concentration,
      was constructed from the data from all the experiments. Active tubular secretion
      was calculated for each experiment separately by subtracting the famotidine
      filtration rate from the total excretion rate. A tubular transport maximum of
      2400 +/- 220 micrograms min-1 and an apparent Michaelis-Menten constant for
      tubular secretion of 26 +/- 4 micrograms mL-1 (76 +/- 12 microM) were estimated
      from the curve. To the best of our knowledge, this is the first time that
      saturation of famotidine renal clearance has been fully quantified in-vivo.
      Considering the low therapeutic plasma concentrations of famotidine (< 0.1
      microgram mL-1), these results suggest that clinically the drug has a low
      interactive potential.

PMID- 9231348
TI  - Kinetics of bupivacaine after levcromakalim treatment in mice.
AB  - Previous workers have reported that 0.01 mg kg-1 of levcromakalim injected
      intraperitoneally did not modify bupivacaine-induced neurotoxicity but increased
      the duration of action of bupivacaine. This study was designed to document
      possible changes in the pharmacokinetic behaviour of bupivacaine and its main
      metabolite, N-desbutylbupivacaine in mice after a single 0.01 mg kg-1
      intraperitoneal injection of levcromakalim. The kinetic parameters of bupivacaine
      were determined after a single 20 mg kg-1 intraperitoneal injection of
      bupivacaine in controls and in levcromakalim-treated mice. It was found that
      levcromakalim did not change any kinetic parameters of bupivacaine or of its main
      metabolite, N-desbutylbupivacaine. The previously reported findings of the
      influence of the low dose (0.01 mg kg-1) of levcromakalim on bupivacaine-induced
      toxicity agree well with the lack of influence of 0.01 mg kg-1 of levcromakalim
      on bupivacaine and N-desbutylbupivacaine pharmacokinetics, although the reported
      increase in the duration of action of bupivacaine after levcromakalim treatment
      can hardly be explained by the pharmacokinetics of bupivacaine when associated
      with levcromakalim. We suggest that levcromakalim might interfere directly with
      ion-channel block caused by bupivacaine by altering conduction properties or
      indirectly by enhancing bupivacaine-induced voltage and time-dependent sodium
      channel block.

PMID- 9231349
TI  - The effect of the calcium antagonist nimodipine on the detoxification of soman in
      anaesthetized rabbits.
AB  - The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance
      of soman from blood was studied in anaesthetized rabbits intoxicated with soman
      (10.8 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and
      femoral artery were used to investigate soman detoxification. The concentrations
      of the soman isomers C+P- and C-P- in blood samples were determined by gas
      chromatography coupled with high-resolution mass spectrometry. During the
      sampling, 15-300 s after soman injection, the soman concentration in control
      animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with
      nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre
      treated with nimodipine the soman concentration was significantly reduced during
      the first minute of sampling. No differences were detected between soman
      concentrations in samples from the heart and femoral artery. Acetylcholinesterase
      inhibition was also used as an indicator of soman activity; there was no
      difference between the activity of this enzyme in different peripheral organs of
      control and nimodipine-treated animals. Nimodipine reduces the initial
      concentration of soman in the blood, which might be of significance in the
      treatment of soman intoxication.

PMID- 9231350
TI  - Neuromuscular and microvascular changes associated with chronic administration of
      an extract of Teucrium stocksianum in mice.
AB  - This work examines the effect on the weights of vital body organs, on blood
      biochemical variables, on neuromuscular coordination and on cerebral
      microcirculation of aqueous extracts of Teucrium stocksianum, given to mice in
      drinking water at concentrations of 2 and 4% for 56 days. The treatment caused
      progressive impairment of neuromuscular coordination, as evidenced by the time
      spent on the rota-rod. After photochemical challenge, the time for first
      observable platelet aggregation in arterioles was shorter than for the control
      group by 22 and 45% in the 2 and 4% T. stocksianum-treated groups, respectively.
      Platelet aggregation on the venular side was not affected by the treatment nor
      were microvascular diameters. Treatment with the plant extract produced no
      statistically significant effect on the plasma biochemical variables that are
      considered indices of liver and kidney function. Histologically, brains obtained
      from mice treated with T. stocksianum showed loss of cerebellar Purkinje cells.
      Although it is likely that the accelerated platelet aggregation might have
      contributed to an ischaemic effect which could, at least in part, have caused the
      cytotoxicological changes, this does not exclude the possibility of a direct
      cytotoxicological effect of the plant extract. Further pharmacological and
      toxicological investigations on Teucrium species seem warranted.

PMID- 9231351
TI  - Estimation of the chemosensitizing activity of modulators of multi-drug
      resistance via combined simultaneous analysis of sigmoidal dose-response curves.
AB  - The potency of modulators which re-establish sensitivity of resistant tumour
      cells to cytotoxic drugs is not usually described by ED50 values, even though
      such values are needed for comparison of modulator activity. Various methods are
      reported for the determination of ED50 values of propafenone-type modulators of
      multi-drug resistance in cytotoxicity assays. Best results were obtained by using
      a combined simultaneous analysis of dose-response curve families. This approach
      enables calculation of statistically highly significant ED50 values without any
      data reduction directly from the original data points obtained in daunomycin
      cytotoxicity assays. The method also enables extrapolation of the ED50 values of
      compounds with low activity or poor solubility, or both.

PMID- 9231352
TI  - Age-related changes in [3H]nimodipine and [3H]rolipram binding in the rat brain.
AB  - Ageing is associated with changes in neurotransmission which might be correlated
      with abnormal calcium metabolism. Because there is evidence that nimodipine can
      enhance the learning abilities of ageing animals and rolipram can enhance the
      excitability of neurons, providing a functional basis for cognition-enhancing
      activity, age-related alterations in the binding of voltage-dependent L-type
      calcium channels and calcium/calmodulin-independent cyclic adenosine
      monophosphate-selective phosphodiesterase (cyclic-AMP PDE) were studied in 3-week
      and 6-, 12-, 18- and 24-month-old Fisher 344 rats by use of receptor
      autoradiography. [3H]Nimodipine and [3H]rolipram were used to label the voltage
      dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP
      PDE, respectively. [3H]Nimodipine binding showed no obvious change in all brain
      areas of 12- and 18-month-old rats, as compared with 6-month-old animals. In 24
      month-old rats, however, [3H]nimodipine binding increased significantly in the
      striatum and hippocampal CA3 sector. In contrast, [3H]rolipram binding showed no
      significant change in most brain areas during ageing, except for a transient
      change only in the hippocampal CA1 sector of 12-month-old animals. [3H]Nimodipine
      and [3H]rolipram binding showed a significant increase in some brain areas of 3
      week-old rats compared with 6-month-old animals. The results indicate that in
      rats voltage-dependent L-type calcium channels are more susceptible to ageing
      processes than calcium/calmodulin-independent cyclic-AMP PDE. Our data also
      demonstrate that voltage-dependent L-type calcium channels and calcium/calmodulin
      independent cyclic-AMP PDE might play roles in developmental processes. These
      findings might help further elucidation of the relationship between age-related
      neurological deficits and behavioural pharmacology including cognitive function.

PMID- 9231353
TI  - Anticholinergic activity in mice and receptor-binding properties in rats of a
      series of synthetic tropane derivatives.
AB  - A tropane ester, three tropane ethers, atropine and mecamylamine were compared in
      mice for their anti-muscarinic and anti-nicotinic activity against arecoline
      induced tremor and nicotine-induced convulsions, respectively. Their receptor
      binding characteristics were studied in neuronal membranes prepared from rat
      cerebral cortex. The results showed that the tropane ester, 2 alpha R-tropanyl
      benzylate, was more potent than atropine in its anti-muscarinic activity, but the
      anti-muscarinic activity of the tropane ethers, 2 alpha-(2',2'-diphenyl-2'
      hydroxy-ethoxy)tropane (alpha-DPT) and its two isomers (1R,2 alpha R- and 1S,2
      alpha S-) were less potent than that of atropine. In contrast with their anti
      muscarinic potency, 2 alpha R-tropanyl benzylate and the three tropane ethers
      were equipotent in their anti-nicotinic activities. The order of potencies of
      these compounds to displace the binding of [3H]quinuclidinyl benzylate to brain
      membranes was similar to that of their anti-muscarinic potencies. The binding of
      [3H]nicotine to nicotinic receptors from brain was not inhibited by these
      compounds. Analyses of structure-activity relationships of these compounds
      suggested that it is the ester groups that determine the anti-muscarinic
      potencies of 2 alpha R-tropanyl benzylate; their anti-nicotinic activities were
      independent of the structural changes and of the anti-muscarinic activities of
      these compounds.

PMID- 9231354
TI  - A sensitive assay for studying dopaminergic activity in cultures of rat pituitary
      cells.
AB  - The dopaminergic and antidopaminergic activity of drugs is frequently assayed in
      pituitary cell cultures. Here we describe a modified version of the assay based
      on the use of pituitary cells from prepubertal female rats. Under our
      experimental conditions (50,000 cells well-1, 2-day culture and 2-h drug
      exposure) the assay yielded high selectivity and sensitivity for drug
      dopaminergic activity. D2 agonistic activity of bromocriptine could be observed
      at a concentration as low as 10(-15) M, the antagonistic activity of haloperidol
      at 10(-16) M. The assay also proved reproducible and simple enough for routine
      screening of dopaminergic activity. The assay enabled dopaminergic agonist and
      antagonist activity to be revealed at very low drug concentrations. The high
      sensitivity of the assay could be of advantage in studying dopaminergic activity
      in samples containing active substances present at low concentrations or for
      disclosing the activity of substances with low dopaminergic potency.

PMID- 9231355
TI  - Influence of certain calcium-channel blockers on some aspects of lorazepam
      dependence in mice.
AB  - The effect of acute and chronic treatments of the calcium-channel blockers,
      isradipine, diltiazem and flunarizine in protecting against lorazepam dependence
      has been demonstrated in mice. Dependence was induced by twice-daily
      administration of lorazepam (1 mg kg-1) for 10 days, doubling the dose during the
      next 10 days. Withdrawal symptoms and changes in the noradrenaline, dopamine and
      5-hydroxytryptamine content of different regions of the brain were observed after
      either 24-h withdrawal or flumazenil administration. Isradipine inhibited
      lorazepam withdrawal symptoms, the effect being accompanied in the 24-h
      withdrawal group by significant decreases in the noradrenaline and dopamine
      content of the thalamus and hypothalamus and in the noradrenaline content of the
      mid-brain. In the flumazenil-treated group isradipine produced significant
      decreases in mid-brain noradrenaline and dopamine levels and in the dopamine
      content of the thalamus and hypothalamus. Diltiazem did not, on the other hand,
      afford significant protection against lorazepam withdrawal symptoms and did not
      induce any significant change in the neurotransmitters studied. Flunarizine
      significantly inhibited lorazepam withdrawal symptoms, an effect accompanied by
      significant reduction in noradrenaline and dopamine levels in the thalamus and
      hypothalamus. Dopamine was also significantly reduced in the cerebral cortex.
      Similar effects were produced in the flumazenil-treated group, and the
      noradrenaline content was reduced in the medulla, pons and cerebellum. It was
      concluded that isradipine and flunarizine might be of value in ameliorating
      lorazepam withdrawal symptoms.

PMID- 9231356
TI  - The effects of a triterpene fraction isolated from Crataegus monogyna Jacq. on
      different acute inflammation models in rats and mice. Leucocyte migration and
      phospholipase A2 inhibition.
AB  - The plant Crataegus monogyna has action against cardiac insufficiency, angina and
      arrhythmia. The anti-inflammatory properties of the cycloartenol fraction from
      this plant have been investigated. Chromatographic fractionation of the hexane
      extract of Crataegus monogyna Jacq. (Rosaceae) furnished a triterpene fraction
      containing cycloartenol as the main component (80.87%). The anti-inflammatory
      activity of the fraction was tested against hind-paw oedema induced by
      carrageenan in rats. At the highest oral dose (40 mg kg-1) inhibition was 61.5
      and 52.5% at 3 and 5 h respectively. In the mouse carrageenan peritonitis test,
      the triterpene fraction given orally inhibited peritoneal leucocyte infiltration
      (41.9, 64.7 and 89.4% at 10, 20 and 40 mg kg-1, respectively). The fraction also
      showed weak inhibition of phospholipase A2 (PLA2) in-vitro. These results suggest
      that the fraction containing cycloartenol as the main component exerts an
      important anti-inflammatory action in-vivo by reducing the oedema.

PMID- 9231357
TI  - Comparison of HPLC and enzymatic recycling assays for the measurement of oxidized
      glutathione in rat brain.
AB  - Glutathione (reduced, GSH and oxidized, GSSG) concentrations were analysed in rat
      cerebellar homogenate using high performance liquid chromatography with
      ultraviolet detection (HPLC-UV) or enzymatic recycling assays. GSSG levels found
      using the HPLC-UV assay were 200-fold higher than those obtained with the
      enzymatic recycling procedure. Reduction of synthetic GSSG by glutathione
      reductase showed total conversion to GSH as assessed by HPLC-UV analysis. In
      contrast, only approximately 50% of the HPLC peak for GSSG could be reduced by
      glutathione reductase. Increasing the period of incubation with glutathione
      reductase for longer than 15 min did not alter GSSG levels. These results suggest
      that another substance present in brain tissue is derivatized and eluted at the
      same time as GSSG using the HPLC-UV assay, thus contributing to the apparently
      high GSSG levels found employing this technique.

PMID- 9231358
TI  - Antidiabetic efficacy of BRL 49653, a potent orally active insulin sensitizing
      agent, assessed in the C57BL/KsJ db/db diabetic mouse by non-invasive 1H NMR
      studies of urine.
AB  - High resolution 1H nuclear magnetic resonance (NMR) spectroscopic analysis of
      biofluids is a recently established tool for evaluating inherited and acquired
      errors in metabolic control. In the present study 1H NMR analysis of urine was
      used to monitor efficacy of BRL 49653, a potent and selective antihyperglycaemic
      agent, following oral administration for up to 36 weeks to the genetically
      diabetic C57BL/KsJ db/db mouse. The effects of BRL 49653 on carbohydrate and
      fatty acid metabolism were monitored by determination of changes in
      concentrations of low molecular weight urinary metabolites. A qualitative
      comparison of the NMR spectra of urine from untreated diabetic mice with those of
      lean littermates and literature examples revealed several abnormalities, the
      majority of which could be explained in terms of the non-insulin dependent
      diabetes syndrome exhibited by these animals. Quantitatively the most prominent
      was the extreme glycosuria of both young (8-12 weeks; 0.9 g glucose kg-1 h-1) and
      older (42 weeks; 2 g glucose kg-1 h-1) diabetic mice. This was accompanied by the
      excretion of a number of unassigned sugar derivatives and by ketone bodies.
      Administration of BRL 49653 (3 mumol kg-1) to db/db mice for 24 days reduced
      blood glucose concentrations to values comparable with non-diabetic lean
      littermates and reduced glycosuria by > 90%. BRL 49653 significantly reduced
      excretion of unassigned sugars, acetate, lactate, and the ketone bodies,
      acetoacetate, 3-D-hydroxybutyrate and acetone. The anti-diabetic efficacy of BRL
      49653, assessed from the pattern of urinary metabolites, was maintained over a 36
      week treatment period. These results demonstrate the value of 1H NMR to evaluate
      non-invasively the efficacy of novel therapeutic agents.

PMID- 9231359
TI  - Peculiarities of the osmotic response in dehydrated erythrocytes.
AB  - Human erythrocytes were dehydrated in concentrated sucrose solutions and
      rehydrated in isotonic NaCl solution. The osmotic responses of erythrocytes
      dehydrated in media with osmolarities over 1 M corresponded to the ideal osmotic
      behaviour. This was also true of the ghosts formed during rehydration of
      dehydrated erythrocytes irrespective of the initial osmolarity. Fresh
      erythrocytes as well as erythrocytes dehydrated in sucrose media with osmolarity
      of 0.5-0.6 M displayed nonideal responses (volume changes were lower than
      predicted). In contrast to the cells dehydrated at 0 degree C, the peculiarities
      of the osmotic response of the cells dehydrated within the osmolarity range of
      0.7-0.8 M at 37 degrees C can be detected spectrophotometrically. The data
      obtained suggest that the nonideal osmotic response of human erythrocytes is
      probably due to a specific state of hemoglobin.

PMID- 9231360
TI  - In vitro effect of hydrocortisone on calcium distribution in rat thymocytes.
AB  - Chlorotetracycline (CTC) was used as a fluorescence indicator to investigate the
      intracellular membrane-bound Ca2+ redistribution in the hydrocortisone (HC)
      treated rat thymocytes. The effect of HC (0.1-1 microM) on the thymocytes
      incubated in Ca2+ containing media for 60-120 min increased 1.5-fold the quantity
      of membrane-bound Ca2+ in the plasma membrane. When thymocytes were incubated in
      Ca(2+)-free media, no HC-induced changes in the Ca2+ pool of plasma membrane were
      revealed. In the presence of inhibitors of respiration and oxidative
      phosphorylation, the CTC fluorescence intensity in the HC-treated cells decreased
      to a greater extent than in the control, thereby indicating an increase in the
      mitochondrial Ca2+ pool. Using inhibitors of endoplasmic reticulum Ca(2+)-ATPase
      (vanadate, BHQ). HC was shown to decrease the non-mitochondrial Ca2+ pool.
      Calmodulin blockers (triphthasine and R24) slightly decreased the CTC
      fluorescence intensity in the HC-treated cells as compared to the control. HC was
      found to inhibit the calmodulin-mediated Ca2+ accumulation in the thymocyte
      membrane. Based on the experiments using AlF4, we concluded that HC stimulates
      the activity of G-proteins through the receptor-mediated mechanism. A possible
      role of the observed Ca2+ redistribution between the thymocyte intracellular
      compartments, specifically between mitochondria and reticulum, is discussed.

PMID- 9231361
TI  - Effects of triton X-100 and concanavalin A on the properties of 5'-nucleotidase
      in rat liver and adipose plasma membranes: a role of membrane structure in the
      regulation of enzyme activity.
AB  - The kinetic and thermodynamic properties of 5'-nucleotidase (EC 3.1,3.5) were
      investigated in rat liver and adipose plasma membranes (PM) after their
      structural modification with nonionic detergent Triton X-100 (TX-100) or lectin
      concanavalin A (Con-A). The apparent K(m) value of 5'-nucleotidase decreased
      after PM treatment with subsolubilizing TX-100 concentrations (0.005-0.015%) and
      then tended to grow at higher TX-100 concentrations (0.03-0.05%). Treatment of PM
      with Con-A resulted in the noncompetitive inhibition of 5'-nucleotidase in a dose
      dependent manner. The Arrhenius plot of the 5'-nucleotidase activity in the
      control PM exhibited a single well defined break at about 28-31 degrees C with a
      lower activation energy at the upper slope of the graph. The shape of the
      Arrhenius graphs and the thermodynamic parameters of 5'-nucleotidase were
      specifically modified upon the PM treatment with increasing concentrations of TX
      100 or Con-A. It was suggested that the functional activity of 5'-nucleotidase
      and its conformation within the membrane matrix may be directly regulated by the
      structural states of the enzyme specific microenvironment and of the membrane
      lipid bilayer. Moreover, the existence of the spatial and/or compositional optima
      for the relationship between the enzyme molecule and its lipid surrounding may be
      reasonably supposed.

PMID- 9231362
TI  - The spatial structure of lipids in human leukocytes: studies by nonradiative
      energy transfer.
AB  - The spatial structure of lipids in living human lymphocytes and granulocytes has
      been studied using the energy transfer between lipophilic fluorescent probes. One
      of the probes, an energy donor (DMC), was localized in the lipid interior,
      whereas another donor (K-68) and an energy acceptor (DSP-12) were near the
      lipid/water interface. The energy transfer in lymphocytes was the same as in
      artificial lipid membranes (liposomes). Obviously, in lymphocytes as in
      liposomes, both donors are localized near the lipid surface (the distance from
      the donors to the lipid surface is less than Forster's radius R0, i.e., 3.4-5
      nm). On the contrary, in granulocytes, the energy transfer from K-68 was 2.2
      times more efficient than from the lipid-immersed DMC. It was suggested that a
      fraction of DMC molecules was immersed into some lipid particles, and the
      distance from the molecules to the surface of the particles was greater than R0.
      The positions of the DMC fluorescence spectrum maxima in lymphocytes and in
      liposomes were the same, but in granulocytes the spectrum was blue-shifted (as in
      the case of lipoproteins). After subcellular fractionation the DMC fluorescence
      intensity correlated only with phospholipid concentration in different fractions
      but not with protein or nucleic acid concentrations. It was suggested that lipid
      organelles are the main source of the DMC fluorescence. The studies of cell
      lipoprotein model mixtures support the suggestion that lipids in lymphocytes are
      mainly present as lamellar structures (membranes); the presence of lipoprotein
      like particles of rather small radius can not be excluded either. On the other
      hand, in addition to membrane lipids, granulocytes have lipid-containing
      particles similar to large serum very low density lipoproteins.

PMID- 9231363
TI  - Redistribution of lipid probes at early stages of bilayer lipid membrane fusion.
AB  - Redistribution of hydrophobic probes (R18 and dipicrylamine DPA-) through a water
      gap between two bilayer lipid membranes (BLM) was studied. Both probes are widely
      used for monitoring lipid redistribution in different cell systems. The donor
      membrane loaded with the probe was brought into a close contact with the acceptor
      membrane, and the redistribution of the probe, was recorded as changes in the
      permittance of the acceptor membrane. It was shown that DPA- easily penetrated
      the water gap, whereas R18 was not detected in the acceptor membrane 30 min after
      the close contact formation. After fusion, R18 rapidly spread into the acceptor
      membrane; hence, only R18 reflects the behaviour of membrane lipids in the fusion
      process.

PMID- 9231364
TI  - Effects of triterpenoid glycosides of the dammaran series and their aglycons on
      phase transitions of dipalmitoylphosphatidylcholine.
AB  - The effects of triterpenoid glycosides from Korean red ginseng Panax C.A. Meyer
      and their aglycons on the phase transitions of model DPPC membranes were studied
      by microcalorimetry. Glycosides Rb1, Rg1, 20(S) protopanaxadiol only slightly
      interacted with the DPPC gel phase and caused no formation of new phases. At
      concentrations close to equimolar values, the glycosides slightly disturbed the
      packing of lipids and induced the formation of the second phases with more dense
      lipid packing but smaller sizes of the cooperative domains as compared with pure
      lipid. Cholesterol (3%) produced no effect on the DPPC interaction with Rb1, Rg1
      and panaxatriol but affected the DPPC interaction with panaxadiol. At equimolar
      panaxadiol/DPPC ratio and in the presence of 3% cholesterol, panaxadiol
      completely eliminated the main transition.

PMID- 9231365
TI  - Interaction of copper ions with stearic acid Langmuir monolayers and formation of
      cluster structures in monolayers and Langmuir-Blodgett films.
AB  - The interaction of copper ions with a stearic acid Langmuir monolayer resulting
      in an extremely high level of copper binding to the monolayer in amounts much
      larger than the number of stearic acid molecules in the monolayer was studied.
      The shape of the pressure-area isotherm changed drastically upon pH changes from
      4 to 6 in the presence of copper ions in the aqueous phase (at concentrations of
      10(-5) to 10(-3)(M) or upon addition of copper ions to the aqueous phase under
      different monolayer compressions. The copper ion concentration changes in the
      bulk phase, caused by binding to the monolayer, were studied by EPR at the
      equilibrium after intensive mixing of the bulk phase and were found to depend on
      pH of the aqueous phase and the extent of monolayer compression. The highest
      level of binding (up to 100 copper ions per stearic acid molecule, pH 5.6,
      initial copper concentration 5.10(-4) M) was observed at a surface pressure of
      about 20 mN/m; further compression of the monolayer and the respective increase
      in surface pressure caused the reverse growth of aqueous phase copper ion
      concentration. At the collapse and destruction of the monolayer, the copper ion
      concentration in the bulk phase was similar to that in the absence of the
      monolayer. The EPR spectra and SAXS diffractograms of copper-containing stearic
      acid monolayers confirmed the high copper content in LB films obtained. An STM
      study of pure stearic acid and the copper-containing monolayer LB films,
      transferred to graphite wafers from the water subphase surface (pH 5.4) at
      various copper concentrations, discovered nanosized (about 5 nM) cluster
      formations on the monolayer surface. The data obtained indicate that the
      interaction of a charged Langmuir monolayer with copper ions and formation of
      copper-containing nanostructures depends on monolayer compression and is
      determined by the arrangement, order, mobility of the monolayer stearic acid
      molecules and by electrostatics at the interface.

PMID- 9231366
TI  - Reversibility of structural rearrangements in lipid membranes induced by
      adsorption-desorption of a polycation.
AB  - Interaction of poly(N-ethyl-4-vinylpyridinium bromide) with mixed
      cardiolipin/phosphatidyl-choline (1/9) liposomes was studied by differential
      scanning calorimetry and photon correlation spectroscopy. It was found that the
      adsorption of polycation on the surface of liquid liposomes was accompanied by
      transmembrane migration of negatively charged cardiolipin molecules from the
      inner to outer membrane leaflet and lateral lipid segregation. At the same time,
      the liposome integrity was retained, and the adsorbed polycation can be displaced
      from the membrane by recomplexation with polyanions. As a result, the initial
      transmembrane and lateral lipid distribution in the membrane was restored.

PMID- 9231367
TI  - Langmuir films from antibodies based on amphiphilic polyelectrolytes.
AB  - A technique for forming Langmuir films from antibodies based on an amphiphilic
      polyelectrolyte was developed. The physicochemical and immunochemical properties
      of the Langmuir films obtained were studied. The interaction of HBsAg with the
      films was found to be described by a model with one binding site, whereas that of
      HBsAg with antibodies adsorbed on a polystyrene plate, by a model with a positive
      cooperativity. The use of the novel Langmuir films from antibodies increases the
      sensitivity of the immunoenzyme assay.

PMID- 9231368
TI  - A mechanism of skin appendage macropores electroactivation during iontophoresis.
AB  - A physical mechanism of activation of skin appendage macropores under the
      influence of an electric field is considered theoretically. The macropore is
      considered as a long cylinder tube which is closed and flattened out before the
      electric field is applied. The charging of the capacitance of the macropore walls
      is the driving force of electroactivation. During this process the free energy of
      the system decreases, which is energetically favourable and results in water
      pulled into the tube and to a gradual opening of the tube. It is shown that
      consideration of the macropore wall conductance leads to a considerable slowdown
      of electroactivation. The opening time of a separate macropore is estimated. It
      is equal to 30 min for a macropore 4 mm in length. The dependence of the surface
      density of activated macropores on time is calculated theoretically. The obtained
      theoretical results are in a good agreement with the literature data.

PMID- 9231369
TI  - A possible role of the redox interactions in the dual, activatory and inhibitory,
      action of DPI 201-106 on the potential-dependent Na+ channels.
AB  - Dual, activatory and inhibitory, effects of a cardiotonic drug DPI 201-106 on Na+
      channels were compared with the redox properties of the DPI itself and of the
      constituents of its molecule, indole and piperazine. The indole component
      accepted electrons from radical intermediates of the light excited dye; the
      piperazine part of DPI acted as an electron donor in the same radical reactions.
      These data extend the previously obtained results which characterized organic
      blockers of Na+ and Ca2+ channels as electron donors, whereas activators of these
      channels were shown to be electron acceptors in test radical reactions. The whole
      DPI 201-106 molecule revealed both the electron-donor and electron-acceptor
      activity. The described electrophysiological effects of this compound (G. Wang et
      al., 1989) are discussed within the framework of the Na+ channel redox model (B.
      Marinov, 1991).

PMID- 9231371
TI  - Effect of temperature on oxygen stores during aerobic diving in the freshwater
      turtle Mauremys caspica leprosa.
AB  - Oxygen stores available for aerobic diving were studied in the freshwater turtle
      (Mauremys caspica leprosa) at three constant body temperatures (15 degrees, 25
      degrees, and 35 degrees C) and during the thermal transient (30 degrees-15
      degrees C) induced by immersion in cold water. The term "aerobic dive limit" has
      been defined as the maximal duration of the dive before lactate increases. This
      increase occurs when a critical PO2 value is reached, and it is well
      characterized at lung level by a sharp increase in the lung apnoeic respiratory
      quotient. Kinetic analysis of lung gas composition during forced dives at fixed
      body temperature shows that critical PO2 values rise with temperature and that
      the postventilatory PO2 at the beginning of a dive decreases, so that the two
      temperature-dependent factors lead to a significant decrease with temperature in
      the lung O2 stores available for aerobic diving. During dives with transient body
      cooling, a natural condition in M. caspica leprosa, temperature equilibration
      occurs fast enough to expand aerobic scope by bearing the critical PO2 to the
      same value obtained at a fixed temperature of 15 degrees C. These dives are
      characterized by reversed CO2 transport (from lung to tissues) and therefore by
      negative values of the lung respiratory quotient; a decrease in temperature
      increases CO2 capacitance of tissues, resulting in a fall in PCO2 at constant CO2
      content. Because this does not occur in the gas phase, PCO2 difference can lead
      to diffusion in the direction opposite from normal. This pattern may favour lung
      to-tissue O2 transfer, through the Bohr effect. Therefore, the aerobic dive limit
      is reduced at high temperature not only through a metabolic rate effect but also
      through a marked decrease in the available O2 stores; fast body cooling (30
      degrees-15 degrees C) associated with immersion in cold water extends the O2
      stores available for aerobic diving to a level similar to that of immersions at
      constant body temperatures that are in equilibrium with water temperature.

PMID- 9231370
TI  - The ctenophore Mnemiopsis leidyi has a flow-through system for digestion with
      three consecutive phases of extracellular digestion.
AB  - The ctenophore (comb jelly) Mnemiopsis leidyi is a periodically abundant and
      voracious predator in U.S. coastal waters. Mnemiopsis leidyi is especially
      competitive at high prey concentrations because of its very efficient
      extracellular digestion. We investigated the functional basis for these
      outstanding digestion capabilities. Extracellular digestion takes place in the
      pharynx and consists of three distinct and consecutive phases. The three phases
      take place in different regions of the pharynx so that various prey items can be
      treated simultaneously in each phase. The first phase is acidic, while the second
      and the third are alkaline. Extracellular digestion is completed by ciliary
      currents that mechanically disrupt the predigested food. Bulky indigestible food
      fragments are expelled through the mouth. Except for a small area, the paths for
      ingestion and egestion are separate. Hence, both ingestion and egestion can occur
      simultaneously. The flattened and elongated shape of the pharynx provides the
      morphological basis for this flow-through system with various regions for
      different digestive treatments of the food. This system is highly elaborated
      compared with those of other lower invertebrates and allows for an efficient,
      fast, and simultaneous digestion of many prey items, which accounts for the
      outstanding feeding capabilities of M. leidyi.

PMID- 9231372
TI  - Validation of the doubly labeled water method in bald eagles (Haliaeetus
      leucocephalus) and a comparison of two equations for the calculation of energy
      expenditure.
AB  - We validated the doubly labeled water (DLW) technique for measurement of energy
      expenditure in bald eagles (Haliaeetus leucocephalus) in captivity by
      simultaneously measuring metabolizable energy intake in a feeding trial. We
      calculated CO2 production using two equations, one typically used by animal
      ecologists (the "one-pool" equation) and the other typically used by human
      nutritionists (the "two-pool" equation). Metabolizable energy intake, as
      determined by feeding trials, for two adult eagles eating rats averaged 1,160 +/-
      89 kJ d-1 and for four nestlings eating fish averaged 2,124 +/- 40 kJ d-1. Energy
      expenditure measured from DLW turnover using the one-pool equation averaged 2.2%
      +/- 7.1% higher than metabolizable energy intake measured by feeding trials (not
      significantly different, P > 0.50), but when the two-pool equation was used,
      energy expenditure measured with DLW averaged 17.7% +/- 6.7% lower than
      metabolizable energy intake measured by feeding trials (significantly different,
      0.025 < P < 0.05). Thus, the use of the DLW technique with CO2 production
      calculated by the one-pool equation was validated for bald eagles.

PMID- 9231373
TI  - The energy assimilation efficiency of emperor penguins, Aptenodytes forsteri, fed
      a diet of Antarctic krill, Euphausia superba.
AB  - Captive emperor penguins in Antarctica hand-fed Antarctic krill assimilated an
      average of 70.5% +/- 1.7% (n = 3) of the energy in the diet. Water intake
      estimated by tritiated water turnover was 9.4% +/- 2.4% less than that measured
      gravimetrically. Tritium took 1.5 h from injection to equilibrate with the
      penguins' body water pools.

PMID- 9231374
TI  - Seasonal variations in the temperature acclimation response of the channel
      catfish, Ictalurus punctatus.
AB  - Channel catfish were collected on 11 different dates from October 1991 to July
      1993 and acclimated in the laboratory to 7 degrees C, 15 degrees C, or 25 degrees
      C for 6 wk. Hepatosomatic index, mg protein mg-1 DNA, total liver DNA and
      protein, and the activities of liver glucose-6-phosphate dehydrogenase, 6
      phosphogluconate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase
      were measured to examine seasonal variation in the acclimation response. Liver
      and muscle cytochrome oxidase and lactate dehydrogenase activities were measured
      to compare tissue-specific responses. Hepatosomatic indexes of fall and winter
      channel catfish were highest at 7 degrees C, with values at 15 degrees C higher
      than at 25 degrees C, while spring and summer fish had the highest values at 15
      degrees C, with values at 7 degrees C higher than those at 25 degrees C.
      Acclimation patterns for total liver protein and DNA, mg protein mg-1 DNA, and
      glycogen were generally higher in cold temperatures but varied seasonally in an
      unpredictable manner. Glucose-6-phosphate dehydrogenase, 6-phosphogluconate
      dehydrogenase, and malate dehydrogenase demonstrated positive acclimation in the
      fall and winter; fish collected in the spring and summer showed little or inverse
      acclimation. Liver lactate dehydrogenase activity showed little or no positive
      compensation at any time of the year. Cytochrome oxidase activity showed positive
      acclimation in muscle but not liver. All liver enzymes, even those that showed
      marginal acclimation on a protein basis, showed positive acclimation when
      activity was expressed on a whole-liver basis.

PMID- 9231375
TI  - Respiratory exchange and ventilation during nocturnal torpor in hummingbirds.
AB  - In mammals that undergo torpor and hibernation, a period of CO2 storage is often
      a prelude to, and may be required for, the onset of a bout of torpor. Storage of
      CO2 has been hypothesized to induce an energy-conserving metabolic suppression in
      torpid mammals. It is unclear whether CO2 storage also occurs in birds that
      undergo torpor. To study these questions, we measured rates of oxygen consumption
      (VO2) and carbon dioxide production (VCO2) during normothermy, entrance into
      torpor, steady-state torpor, and spontaneous arousal in Selasphorus hummingbirds.
      The respiratory exchange ratio (RER) declined from about 0.86 to about 0.71 in
      both normothermic and torpid individuals, suggesting a shift from carbohydrate
      oxidation to lipid oxidation during the night. Torpor metabolism ranged from 5%
      to 42% of normothermic values. In most individuals that became torpid, a brief
      period of CO2 storage occurred during entrance into torpor, beginning after VO2
      had fallen considerably below normothermic rates. The volume of CO2 stored
      averaged 0.048 mL CO2 g-1, somewhat less than reported for mammalian hibernators.
      Some individuals entered torpor without measurable CO2 storage. There was no
      abrupt change in RER at the start of arousal, although mean arousal RER exceeded
      the RER during steady-state torpor. The change in metabolic rate between
      normothermia and torpor had a Q10 of 1.9-2.2 in birds that did not regulate body
      temperature in torpor. We conclude that a normal Q10 effect is sufficient to
      explain the metabolic rate of torpid hummingbirds and that transient CO2 storage
      may occur during entrance into torpor but is not a prerequisite for entrance.
      Similarly, CO2 release is not a prerequisite for arousal.

PMID- 9231376
TI  - Body temperatures and activity patterns of Tasmanian devils (Sarcophilus
      harrisii) and eastern quolls (Dasyurus viverrinus) through a subalpine winter.
AB  - During a field study of carnivorous dasyurid marsupials in subalpine Tasmania,
      the trapping success for Tasmanian devils (Sarcophilus harrisii), but not for
      spotted-tailed quolls (Dasyurus maculatus) or eastern quolls (Dasyurus
      viverrinus), was significantly lower when winter weather conditions turned to
      sleet or snow or when deep snow lay on the ground. This field study was
      instigated to determine if devils and eastern quolls spend more time in burrows
      in severe weather conditions and if they enter torpor. Torpor is known to occur
      in eutherian mammals as large as devils and in a similar-sized congeneric
      marsupial, the western quoll (Dasyurus geoffroyi). Using radiotelemetry, body
      temperatures of Tasmanian devils and eastern quolls ranging freely in their
      natural habitat were monitored throughout winter. Neither species was observed in
      torpor, even under prolonged severe weather conditions, and the number of hours
      spent active not did differ between summer and winter or between moderate and
      severe winter weather conditions. Body temperatures averaged 36.5 degrees C (SD =
      0.079, range of 33.5 degrees-38.6 degrees C) for the three male eastern quolls
      and 35.7 degrees C (SD = 0.575, range of 31.3 degrees-37.5 degrees C) for the
      four (male and female) devils. A diel cycle in body temperature occurred in both
      species; temperatures rose each evening when animals became active, remained high
      throughout the night despite ambient temperatures falling to the diel minima, and
      were lower during the day when the individuals were inactive in dens. The
      amplitude of this cycle was greater in eastern quolls (1.1 degrees C, SD = 0.142)
      than in devils (0.6 degree C, SD = 0.252).

PMID- 9231378
TI  - Corticosterone, reproductive status, and body mass in a cooperative breeder, the
      Florida scrub-jay (Aphelocoma coerulescens).
AB  - In the cooperatively breeding Florida scrub-jay, nonbreeders are subordinate to
      the breeders with which they share a territory. Corticosterone is secreted in
      response to a wide range of stressors, including social stress, and suppresses
      reproductive and territorial behaviors in several taxa; thus, elevated baseline
      levels of corticosterone might be a causal mechanism of reproductive suppression.
      To test the hypothesis that nonbreeder Florida scrub-jays are reproductively
      suppressed through the actions of corticosterone, we compared corticosterone
      levels of nonbreeders and breeders and found no differences. However, baseline
      corticosterone levels only provide information about a bird's current hormonal
      status. Virtually all species exhibit a rapid rise in glucocorticoids in response
      to an acute stressor. If the adrenocortical response of nonbreeders is greater
      than that of breeders, this might be a mechanism whereby nonbreeders remain
      reproductively quiescent. We compared the responses of breeders and nonbreeders
      to the acute stress of being captured and held for 1 h. Both exhibited
      significant but equivalent increases in corticosterone titers. Because in some
      species heavier or fatter individuals have reduced glucocorticoid responses to
      stressors, we examined whether body mass was correlated with corticosterone
      titers. Both baseline and maximum corticosterone levels covaried with body mass,
      and the effect of body mass on corticosterone levels explained the increase due
      to capture and handling. Our data do not support the hypothesis that Florida
      scrub-jay nonbreeders are reproductively suppressed through the actions of
      corticosterone.

PMID- 9231377
TI  - Glycolytic enzyme binding during entrance to daily torpor in deer mice
      (Peromyscus maniculatus).
AB  - Associations of glycolytic enzymes with the subcellular particulate fraction of
      skeletal muscle and heart were examined during entrance to daily torpor in deer
      mice (Peromyscus maniculatus). In skeletal muscle a significant decrease in
      enzyme binding occurred during torpor entrance for phosphofructokinase,
      glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase, with an additional
      significant decrease for phosphofructokinase and pyruvate kinase during the
      deepest state of torpor. Reductions in enzyme binding during torpor entrance also
      occurred in heart; significant changes were observed in hexokinase,
      glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase binding. Contrary
      to the finding of additional reductions in enzyme binding seen in skeletal
      muscle, significant increases in enzyme binding during the deepest torpor state
      were observed for hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate
      dehydrogenase, pyruvate kinase, and lactate dehydrogenase in heart. These results
      suggest that a decrease in the binding of glycolytic enzymes to subcellular
      structures in skeletal muscle and heart may be at least partially responsible for
      initiating the reduction in metabolic rate during torpor entrance. This decreased
      binding may continue to mediate the metabolic reduction in skeletal muscle
      throughout torpor; heart, however, may require the use of different molecular
      mechanisms. The increased binding in heart during the deepest state of torpor may
      represent an anticipatory response in preparation for increased activity during
      arousal.

PMID- 9231379
TI  - Timing of the calcium intake and effect of calcium deficiency on behaviour and
      egg laying in captive great tits, Parus major.
AB  - The calcium demand of egg-laying birds is much higher than in other vertebrates
      during reproduction. We showed elsewhere that a low level of calcium availability
      can greatly affect the eggshell quality and reproduction of free-living
      passerines. However, there are few data on calcium demand and calcium intake in
      relation to egg laying and behaviour and egg-laying performance under conditions
      of calcium shortage in nondomesticated birds. We examined these aspects in an
      experiment with captive great tits, Parus major, on a diet deficient in calcium,
      with or without snail shells as an additional calcium source. More than 90% of
      the calcium intake for egg production took place during the egg-laying period.
      Females ingested about 1.7 times as much calcium as they deposited in eggshells.
      Removing the snail shells after the first egg resulted in eggshell defects and
      interruptions of laying after 1-3 d. Females without snail shells doubled their
      searching effort and started to burrow in the soil and to eat sand, small stones,
      and their own eggs. Most calcium was consumed in the evening, probably to
      supplement the calcium available from the medullary bone with an additional
      calcium source in the gut during eggshell formation. The results demonstrated
      that eggshell formation requires accurate timing of the calcium intake and that
      obtaining sufficient calcium is time-consuming, even in calcium-rich
      environments. These factors pertaining to calcium intake greatly affect the
      ability of birds to collect sufficient calcium for eggshell formation in calcium
      poor areas.

PMID- 9231380
TI  - Ontogeny of the thermal limits in the harbor seal (Phoca vitulina).
AB  - We measured metabolic rates (mL O2 h-1, converted to kcal d-1), deep body
      temperatures (degree C), and skin temperatures (degree C) and calculated whole
      animal thermal conductances (mL O2 g-1 h-1 degree C-1) of five 3-yr-old harbor
      seals (Phoca vitulina concolor) at air temperatures between -20 degrees and 35
      degrees C. The mean thermal neutral zone of these seals extended from a lower
      critical temperature of -12.9 degrees +/- 1.6 degrees C (SD) to an upper critical
      temperature of 28.6 degrees +/- 1.7 degrees C. Hyperthermia was observed at an
      ambient air temperature of 35 degrees C. Mean standard metabolic rate was 1,553.6
      +/- 168.2 kcal d-1, about 1.2 times the value expected for adult animals of
      similar body mass (mean mass = 49.2 +/- 7.5 kg). Mean deep body temperature
      increased from 37.5 degrees +/- 0.30 degrees C at an ambient temperature of 30
      degrees C and reached 39.3 degrees +/- 0.33 degrees C at an ambient temperature
      of 35 degrees C. Skin temperature decreased with decreasing ambient temperature
      but remained well above ambient temperature. Mean whole-animal thermal
      conductance decreased from an ambient temperature of 35 degrees C until it
      reached a minimum value of 0.007 mL O2 g-1 h-1 degree C-1 at -4.0 degrees C; it
      then increased with a further decrease in ambient temperature. In comparison to
      the thermal limits of the same seals during their first year of life, the results
      indicate a broadening of the thermal neutral zone with age: an 11 degrees C
      decrease in the lower critical temperature and a 3.5 degrees C increase in the
      upper critical temperature. These findings suggest that warm ambient air
      temperatures should not pose any particular thermoregulatory problems for larger
      and older harbor seals, even beyond the limits of their current annual
      distribution.

PMID- 9231381
TI  - Sugar digestion efficiencies of Gurney's sugarbirds, malachite sunbirds, and
      black sunbirds.
AB  - This study determined the interaction between energy assimilation and digestive
      constraints on the foraging behaviour of nectarivorous Gurney's sugarbirds
      (Promerops gurneyi), black sunbirds (Nectarinia amethystina), and malachite
      sunbirds (Nectarinia famosa) in the laboratory. Rates of sugar intake and
      consumption, transit time, and the concentration of sugar in the excreta were
      measured when birds were fed 0.25 mol L-1 sucrose, 0.73 mol L-1 sucrose, and 0.73
      mol L-1 glucose. For each species, intake rates by volume were greater at low
      sugar concentrations, such that energy intakes per 90 min were similar,
      irrespective of diet, which supports the idea of regulated energy intake for
      these nectarivorous birds. All species were efficient at energy extraction,
      excreting 1% or less sucrose equivalent irrespective of the initial sugar
      concentration of each diet. Transit times of solutions ingested increased with an
      increase in sugar concentration. Birds maximized energy assimilation on high- and
      low-energy nectar diets by having high extraction efficiencies and short transit
      times. Sugarbird and sunbird foraging behaviours may be limited by digestive
      processes and the cost of carrying high-energy reserves as nectar sugar
      concentration increases.

PMID- 9231382
TI  - Respiratory, acid-base, and metabolic responses of the Christmas Island blue
      crab, Cardisoma hirtipes (Dana), during simulated environmental conditions.
AB  - The dependency of the Christmas Island blue crab, Cardisoma hirtipes, on fresh
      water for respiratory gas exchange and transport was investigated in laboratory
      simulations. The gas exchange rates of air-breathing C. hirtipes were similar to
      those of other land crabs but decreased to 20% in submerged crabs. Crabs with
      access to air maintained arterial and pulmonary O2 content (CO2) and partial
      pressure (PO2), while in submerged crabs the PO2 and CO2 rapidly decreased (by
      50%). There was no anaerobiosis, but haemolymph glucose concentration and cardiac
      output decreased when crabs were submersed, which suggests a hypometabolic state.
      Submersion induced a metabolic rather than a respiratory alkalosis, and since
      respiratory gas exchange was low, CO2 excretion to water was unimportant.
      Cardisoma hirtipes haemocyanin (Hc) has high O2 affinity but low pH sensitivity,
      which facilitates O2 uptake from hypoxic environments. The high Hc-O2 affinity
      supports O2 loading but may prevent access to a venous O2 reserve. Calcium,
      magnesium, and urate, but not L-lactate, were effectors of Hc-O2 affinity. In
      submerged crabs increased circulating urate maintained haemolymph O2 content. The
      CO2 capacitance and nonbicarbonate buffering of the haemolymph were relatively
      low. A significant Haldane effect seemed important for CO2 excretion but would
      require CO2 and O2 exchange to occur at the same organ (gills or lungs).
      Submersion interferes with respiration and is not needed for haemolymph acid-base
      balance; thus; C. hirtipes is an air-breathing crab.

PMID- 9231383
TI  - The influence of habitat and altitude on oxygen uptake in sub-Antarctic weevils.
AB  - Whole-organism oxygen uptake rate and its temperature sensitivity (determined
      using regression analyses and estimates of Q10) were examined in six closely
      related weevil species (Palirhoeus eatoni, Bothrometopus randi, Bothrometopus
      elongatus, Bothrometopus parvulus, Ectemnorhinus similis, and Ectemnorhinus
      marioni) from sub-Antarctic Marion Island over a short time period and using the
      same methods. Bothrometopus elongatus, B. parvulus, and the two Ectemnorhinus
      species have populations at both high and low elevations, and pairwise
      comparisons of these species were made. Regressions of the log of oxygen uptake
      rate on temperature and Q10 values revealed that the Ectemnorhinus species have a
      significantly greater thermal sensitivity than do species in the genera
      Bothrometopus and Palirhoeus. This may be considered an adaptation of the former
      to their moist lowland habitats and the requirements of angiosperm-feeding in E.
      similis. It is argued that elevated oxygen uptake rates and reduced slopes of the
      regression of the log of oxygen uptake rate on temperature in species and
      populations from high altitudes compared with those from low elevations provide
      evidence for metabolic cold adaptation. In addition, it seems likely that
      elevated oxygen uptake rates and their reduced thermal sensitivity within the
      genera Bothrometopus and Palirhoeus are an adaptation to the cold Neogene
      environments they evolved in. However, because data on the more basal taxa in the
      Ectemnorhinus group of weevils are not available, this temperature compensation
      could not be attributed conclusively to adaptation. Q10's of the lowland
      populations of all the species were negatively correlated with body water
      content, and it is suggested that the low temperature sensitivity of metabolism
      in P. eatoni and the Bothrometopus species may also be due to constraints imposed
      on them by their dry habitats.

PMID- 9231384
TI  - Composition of fuel stores and digestive limitations to fuel deposition rate in
      the long-distance migratory thrush nightingale, Luscinia luscinia.
AB  - During their autumn migratory phase, thrush nightingales (Luscinia luscinia)
      previously starved for 2 d were allowed to refuel under three different ambient
      temperature conditions (-7 degrees, 7 degrees, and 22 degrees C). During the
      refueling period, as well as during the preceding control and starvation periods,
      food intake, body mass, and feces production were monitored. In addition, daily
      energy expenditure was measured during the refueling period. The compilation of
      the energy balance during the refueling period revealed an energy density of the
      deposited tissue of 33.6 kJ g-1. Assuming that the deposited tissue consists of
      fat and protein exclusively, with energy densities of 39.6 and 5.5 kJ g-1 wet
      mass, respectively, we estimated the deposited tissue to consist of 82% fat and
      18% wet protein (6% dry protein and 12% water). Nitrogen balances during control,
      starvation, and refueling phases and during a period of prolonged and complete
      starvation indicated that 5% of the nutrient stores consisted of dry protein. Our
      results support recent findings that nutrient stores for migration often contain
      protein in addition to fat and consequently are 15%-25% less energy rich than
      pure fat stores. These proteins might be stored as muscle or other functional
      tissue and may be required to support the extra mass of the stores and/or reflect
      an incapacity of the metabolic machinery to catabolize far exclusively. Fuel
      deposition rate was positively related with ambient temperature, whereas food
      intake rate was unaffected by temperature. These results indicate that the rate
      of fuel deposition is limited by a ceiling in food intake rate; when this ceiling
      is reached, fuel deposition rate is negatively affected by daily energy
      expenditure rate. To a certain extent, the ceiling in food intake rate varies
      depending on feeding conditions over the previous days. These variations in food
      intake capacity probably reflect the building and breakdown of gut tissues and/or
      gut enzyme systems and might be insensible and not evolutionary adaptive.
      Significant energetic costs, however, are probably associated with the
      maintenance of gut tissues. It is therefore feasible that changes in digestive
      capacity are regulated and are directed at energy economization.

PMID- 9231385
TI  - The unusual adrenergic-like excitatory action of acetylcholine on the ventricular
      cardiac muscle of the horned shark, Heterodontus portusjacksoni.
AB  - The atypical excitatory effect of acetylcholine on cardiac ventricular muscle was
      investigated in the horned shark, Heterodontus portusjacksoni. Electrically paced
      ventricular strips produced a massive 391.45% (+/-26.39%) increase in basal force
      of contraction in response to exogenously applied acetylcholine. The response was
      similar in nature to that produced by applied adrenaline, which caused a 382.52%
      (+/-72.47%) increase. The response to acetylcholine was blocked by the muscarinic
      cholinoceptor antagonist atropine and the competitive beta-adrenoceptor
      antagonist propranolol and was reduced by bretylium, an agent known to inhibit
      the release of catecholamines from adrenergic nerves. These findings strongly
      suggest that acetylcholine mediates a localised release of a catecholamine via
      muscarinic cholinoceptors in shark heart. A cholinergically controlled
      catecholamine store has been proposed (cholinergic-adreno complex), implying that
      elasmobranchs may be capable of finer control of cardiac output than has
      previously been suspected. This complex may represent a transitional adrenergic
      state between humoral and neuronal regulation. The spontaneously beating atrium
      showed no evidence of such an excitatory response to applied acetylcholine but
      produced an atropine-sensitive slowing, a response typical of other vertebrates.

PMID- 9231386
TI  - Corticosterone and the stress response in young western screech-owls: effects of
      captivity, gender, and activity period.
AB  - We used a standard handling protocol to examine the stress response of captive
      young western screech-owls during their active (nighttime) and inactive (daytime)
      periods and to compare the stress responses of captive and free-living owls.
      Circulating corticosterone levels were significantly higher during the inactive
      period than in the active period in this nocturnal species. This suggests that
      the daily pattern of corticosterone secretion is reversed in nocturnal birds and
      is correlated with activity period rather than with the light/dark cycle. Young
      (ca. 4-5 mo old) screech-owls of both sexes showed increases in plasma
      corticosterone up to 30 min after capture, followed by significant decreases at
      60 min. This pattern is similar to those of other species of birds examined
      previously, except that decreases in corticosterone at 60 min rarely have been
      observed. Such decreases may be the result of physiological differences between
      adult and young birds, habituation to handling in captive birds, or the effects
      of body condition. Corticosterone levels and the response to capture and handling
      were comparable in captive and free-living owls, which suggests that the captive
      owls were not subjected to chronically high levels of stress.

PMID- 9231387
TI  - Seasonal adjustment of solar heat gain independent of coat coloration in a desert
      mammal.
AB  - Despite the apparent importance of solar radiation as a source of heat for free
      living animals, there exists no substantial body of empirical data describing
      physiological responses to solar radiation under the range of convective
      conditions likely to occur in nature. We therefore quantified effects of
      simulated solar radiation and wind on metabolic heat production in the rock
      squirrel, Spermophilus variegatus. This diurnal mammal inhabits the Sonoran
      Desert and seasonally replaces its pelage in a fashion in which it retains
      constant external appearance but incorporates optical and structural changes that
      are thought to significantly alter heat-transfer properties of the coat. At a
      given wind speed, the presence of 950 W m-2 of simulated solar radiation reduces
      metabolic heat production by 15% (at a wind speed of 4 m s-1) to 37% (at a wind
      speed of 0.25 m s-1). Independent of effects of irradiance, metabolic heat
      production significantly increases with wind speed such that as wind speed is
      increased from 0.25 m s-1 to 4.0 m s-1, metabolic heat production is elevated by
      66% (sunlight absent) or 88% (sunlight present). Previous analyses demonstrated
      that when exposed to identical radiative and convective environments rock
      squirrels with summer pelages accrue solar heat loads 33%-71% lower than those
      experienced by animals with winter coats. This reduction of solar heat gain
      during the extremely hot Sonoran Desert summer apparently constitutes a
      previously unappreciated mode of thermal adaptation by seasonal adjustment of
      radiative heat gain without changes in the animal's appearance.

PMID- 9231388
TI  - Freezing impairment of male reproductive behaviors of the freeze-tolerant wood
      frog, Rana sylvatica.
AB  - The wood frog (Rana sylvatica), a temperate-zone anuran that overwinters within
      the frost zone, is adapted to tolerate the freezing and thawing of its tissues.
      Because the effects of freezing on complex neurobehavioral function are unknown
      and because R. sylvatica encounters subfreezing temperatures during its late
      winter breeding season, we investigated the reproductive behaviors and physiology
      of male frogs after freezing (minimum body temperature, -2 degrees C) and
      postthaw recovery (4 degrees C). In tests simulating conditions at the breeding
      pool, these frogs, which otherwise behaved normally, exhibited reduced mate
      searching effort and fewer assaults on mates and did not amplex females until 16
      24 h after thawing. Although amplectic ability was ultimately restored in most
      frogs, they competed poorly for mates against never frozen controls. Further
      study suggested that the level of behavioral impairment depends on the severity
      of the freezing exposure. During freezing, tissues accumulated large quantities
      of the cryoprotectant glucose and desiccated extensively, responses that promote
      freezing survival. Freezing also caused marked hydroosmotic and metabolic
      perturbations, which may have impaired neuro-behavioral function, perhaps by
      interfering with the processing of audio, visual, and tactile stimuli.
      Individuals that encounter subfreezing temperatures shortly before arriving at
      the breeding pools may incur reduced reproductive success.

PMID- 9231389
TI  - Effects of ambient oxygen tension on flight performance, metabolism, and water
      loss of the honeybee.
AB  - Although the metabolic rate of resting insects is relatively insensitive to
      atmospheric O2 tensions, metabolic rates during flight increase by 20- to 100
      fold above resting levels. In this study we test whether O2 delivery limits
      metabolic rate during unladen hovering flight of the honeybee, Apis mellifera.
      Below 10 kPa PO2, wing-stroke frequency decreased, and at 5 kPa, bees could not
      fly. However, for PO2's ranging from 39 to 10 kPa, metabolic rate and wing-stroke
      frequency were unaffected by PO2. Evaporative water loss rates increased by 40%
      at the lowest O2 tensions, which suggests that flying honeybees compensated for
      decreasing ambient PO2 by modulating convective ventilatory flow. Under normal
      sea-level conditions, O2 delivery does not limit flight metabolic rate in
      unladen, hovering honeybees and does not limit maximal metabolic rate. At
      altitudes above 3,000 m, the convective component of O2 delivery may, however,
      limit flight metabolic rate and flight capacity in honeybees.

PMID- 9231390
TI  - Effect of tannins on galliform cecal partitioning.
AB  - Winter diets of ruffed grouse (Bonasa umbellus) and other galliformes are high in
      tannins. We fed quebracho, a condensed tannin, to ruffed grouse and found no
      effect on dry matter intake or body mass at levels up to 6% of the diet. However,
      a high-fiber diet with 8% quebracho resulted in reduced dry matter intake and
      body mass loss. Grouse could not tolerate a diet with 8% tannic acid, a
      hydrolyzable tannin, which caused a large reduction in dry matter intake and body
      mass. Northern bobwhite (Colinus virginianus) and ruffed grouse responded to
      dietary quebracho tannin by increasing the proportion of digesta that was
      excreted from the ceca. In the northern bobwhite, 59%-76% of the tannin recovered
      from the feces was in cecal feces. There was no difference in average passage
      rates of liquid and fiber digesta, although variation was high in tannin-fed
      birds. The role of the ceca in handling tannin requires further investigation.

PMID- 9231391
TI  - Respiratory, blood-gas transport, and acid-base response of Leptograpsus
      variegatus to long-term immersion and hyposaline exposure.
AB  - The respiratory and acid-base responses of the supratidal crab Leptograpsus
      variegatus to immersion in either 100% or 50% seawater were measured over a 3-wk
      period. Leptograpsus maintained haemolymph PO2 and CO2 during immersion, owing
      partly to elevated cardiac output and without recourse to hyperventilation. Both
      haemolymph PCO2 and CCO2 were reduced following 3 wk of immersion, and L-lactate
      remained low, but nonetheless Leptograpsus exhibited a marked metabolic acidosis.
      Specific responses to 50% seawater exposure were observed in Leptograpsus when
      compared with control crabs immersed in 100% seawater. Improved O2 delivery
      concomitant with elevated perfusion and ventilation maintained haemolymph
      oxygenation. In hyposaline-exposed Leptograpsus, both PCO2 and CCO2 were reduced
      after 24 h, while pH was elevated after 15 min and remained so during the 3-wk
      immersion. The marked acidosis exhibited in Leptograpsus exposed to 100% seawater
      was partially reduced in those in 50% seawater, presumably because of net acid
      excretion associated with elevated Na+ uptake. Immersion of Leptograpsus reduced
      Hc-O2 affinity to a greater extent in hyposaline-immersed individuals, while the
      cooperativity of O2 binding by Leptograpsus Hc decreased at low pH in both
      salinities. When immersed, the respiratory status of Leptograpsus resembles that
      of water-breathing crabs. Exposure to 50% seawater causes a twofold increase in
      energetic cost but does not perturb the immersed condition. The metabolic
      acidosis induced by chronic immersion is partially compensated at the lower
      salinity. Leptograpsus thus has the ability to take advantage of habitats ranging
      from supratidal through brackish to fully marine.

PMID- 9231392
TI  - Mechanical work as a determinant of prey-handling behavior in the tokay gecko
      (Gekko gecko).
AB  - In this study an in vitro analysis of the force and mechanical work required to
      bite prey items of different size and physical character is combined with an in
      vivo analysis of prey-handling behavior in the tokay gecko (Gekko gecko). The
      force required to bite and the work of biting increase with prey size, but the
      rate of increase is prey specific, with crickets (Acheta domestica) requiring
      substantially more force and work per bite than larvae (Galleria mellonella and
      Manduca sexta) for all but the smallest prey. Prey-handling behavior is also prey
      specific. Geckos exert more bites per feeding event on small crickets than on
      small insect larvae, but the number of bites increases faster with prey mass for
      larvae than for crickets. Combination of the in vitro mechanical measurements
      with the in vivo behavior analysis allows the calculation of total mechanical
      work per feeding event and indicates that total work increases with prey size but
      that the difference between prey types is far less than predicted from the
      differences in structural properties of the prey. This occurs because the number
      of bites and work per bite relationships tend to cancel the differences in the
      total work necessary to process each prey type. Thus, when considering the effect
      of prey size, a 13-fold greater rate of increase in bite force and an 18-fold
      greater rate of increase of work per bit for crickets over larvae was partially
      compensated for by a threefold increase in the number of bites used on larvae
      relative to crickets. These results can be interpreted in two ways. The effect of
      mechanical work in feeding behavior suggests that the energetics of jaw adductor
      musculature could play a greater role in governing the feeding behavior of this
      lizard than has previously been expected. Alternatively, the scaling of work in
      feeding over a range of prey sizes suggests distinct differences in the geometric
      features of the prey that determine how they are processed.

PMID- 9231393
TI  - Determinants of the postfeeding metabolic response of Burmese pythons, Python
      molurus.
AB  - The relatively large meal sizes consumed by sit-and-wait-foraging snake species
      make them favorable for investigating specific dynamic action, the rise in
      metabolic rate associated with digestion. Hence, we measured O2 consumption rates
      (VO2) before and up to 20 d after Burmese pythons (Python molurus) either had
      only constricted and killed rodent meals or had also been allowed to consume
      meals ranging in size from 5% to 111% of their body mass. Postprandial VO2 peaked
      within 2 d at a value that increased with meal size, up to 44 times standard
      metabolic rate for the largest meals. In addition to being the largest known
      magnitude of postprandial metabolic response, this also exceeds the factorial
      increase in VO2 during peak physical activity for all studied animals except
      perhaps racehorses. Specific dynamic action, calculated from the extra VO2 above
      standard metabolic rate over the duration of digestion, increased with meal size
      and equaled 32% of ingested meal energy. The allometric exponent for body mass
      was 0.68 for standard metabolic rate, 0.90 for peak postprandial VO2, and 1.01
      for specific dynamic action. Specific dynamic action is higher, and standard
      metabolic rate is lower, in sit-and-wait-foraging snake species than in actively
      foraging snake species. This suggests that sit-and-wait-foraging snakes, which
      consume large meals at long and unpredictable intervals, reduce standard
      metabolic rate by allowing the energetically expensive small intestine and other
      associated organs to atrophy between meals but thereby incur a large specific
      dynamic action while rebuilding those organs upon feeding.

PMID- 9231394
TI  - Is diet shifting facilitated by modulation of intestinal nutrient uptake? Test of
      an adaptational hypothesis in yellow-rumped warblers.
AB  - Yellow-rumped warblers (Dendroica coronata) are one of many avian species that
      change their diet seasonally. Using them, we tested the predictions that uptake
      of D-glucose and the amino acid L-leucine will increase as dietary levels of
      carbohydrate and protein, respectively, are increased and that mediated uptake
      capacity of the entire small intestine will match nutrient loads from daily food
      intake. Birds were fed three semisynthetic diets, formulated from fruit, insects,
      or seeds, for 7 d. Mediated D-glucose uptake in vitro was affected by diet, but
      contrary to our a priori prediction, fruit eaters eating the diet highest in
      carbohydrates had the lowest uptake rate. Na(+)-dependent L-leucine uptake at a
      low concentration (0.01 mmol L-1) was higher in insect and seed eaters, which is
      consistent with the prediction of adaptation to dietary protein, though dietary
      fat may also play a role. Mediated D-glucose uptake summed over small intestine
      length could explain only a small percentage of the estimated whole-animal
      absorption rate. We thus reject the predictions for carbohydrate but suggest an
      alternative interpretation of our results that is consistent with economical
      design.

PMID- 9231395
TI  - Urea recycling in muskrats (Ondatra zibethicus): a potential nitrogen-conserving
      tactic?
AB  - The rate of 14C-urea hydrolysis was determined in 32 field-acclimatized muskrats
      maintained on natural diets during spring, summer, fall, and winter. We
      hypothesized that urea recycling occurs in muskrats during all seasons and that
      the conservation of tissue nitrogen via this mechanism is most prevalent in fall
      and winter, when forage protein levels are lowest. Muskrats exhibited higher
      rates of urea hydrolysis and a lower serum urea nitrogen-to-creatinine ratio in
      fall and winter than in spring and summer. Even after correcting for seasonal
      differences in blood urea pool size, the adjusted rate of urea hydrolysis was 67%
      higher in fall and winter than in spring and summer. There was no evidence that
      the maintenance nitrogen requirements of muskrats fed natural vegetation were
      affected by seasonal changes in the amino acid composition of the diet. We
      suggest that increased levels of urea recycling, coupled with adaptive mechanisms
      for reducing nitrogen excretion and possibly conserving carbon skeletons of
      essential amino acids, may allow muskrats to reduce their nitrogen requirements
      on fall and winter diets. Our finding that 14C-urea hydrolysis occurred during
      all four sampling periods suggests that nitrogen derived from this source may
      also be critical to supporting large hindgut microbe populations that enable this
      rodent to exploit the appreciable fiber content of its aquatic plant diet
      throughout the year.

PMID- 9231396
TI  - Dietary lipid and intestinal brush border membrane phospholipid fatty acid
      composition and glucose transport of channel catfish.
AB  - Although the influences of dietary carbohydrate and protein on intestinal brush
      border membrane functions are well known, the responses to different dietary
      lipids are less clear, particularly for ectotherms. Therefore, we examined
      intestinal brush border membrane phospholipid fatty acid composition and rates of
      glucose transport of catfish fed two diets with different fatty acid profiles.
      Intestinal brush border membranes of fish fed a diet containing stearic acid had
      higher concentrations of monoenes, dienes, and trienes but were lower in polyenes
      and had a lower unsaturation index than those of fish fed a diet with menhaden
      oil. Rates of glucose transport at low, mid, and high temperatures were higher
      for intact tissues and vesicles prepared from the brush border membrane of fish
      fed the stearic acid diet. Our findings indicate that dietary lipids influence
      intestinal brush border membrane fatty acid composition and the relationship
      between temperature and rates of glucose transport. However, we can not exclude
      the possibility that dietary lipids can induce changes in transporter site
      densities and/or the physical characteristics of membrane microdomains in which
      the transporters might reside.

PMID- 9231397
TI  - Energetics, growth, and body composition of Adelie penguin chicks, Pygoscelis
      adeliae.
AB  - Adelie penguins are very abundant in Antarctica and constitute a large biomass of
      predatory consumers in the Antarctic ecosystem. Adelies eat almost exclusively
      krill (Euphausia spp.), and to determine krill requirements by Adelies,
      information on energetics is needed, including energy intake of the chicks. I
      measured energy use and growth in Adelie penguin chicks, using both field and
      laboratory techniques. Field metabolic rate was quite variable, but mass-specific
      rates were not correlated with body mass. Growth followed the logistic equation:
      the growth constant was 0.143 d-1, and the asymptote for growth to fledging was
      3,200 g. Different body organs had similar energy densities (in kilojoules per
      gram of dry mass), and total body energy density did not vary with chick mass.
      However, proportional mass of the skin increased rapidly as chicks grew, making
      the skin an important energy store in larger chicks. Metabolic efficiency
      measured in the laboratory averaged 69% and did not vary with chick mass. Total
      energy ingested over the 50-d development period was 162 MJ, which corresponds to
      approximately 33.6 kg of fresh krill. Previous studies of Adelie energetics have
      focused on adult energy balance and have calculated chick energy requirements
      indirectly on the basis of adults' stomach loads of krill and frequency of
      feeding chicks. Values from previous studies do not agree with those from the
      present study. The method used in the present study is more informative and
      accurate for measuring energy use by chicks, since measurements are made directly
      from chicks.

PMID- 9231398
TI  - Ecophysiological adaptations to dry thermal environments measured in two
      unrestrained Namibian scorpions, Parabuthus villosus (Buthidae) and
      Opisthophthalmus flavescens (Scorpionidae).
AB  - The daily changes in body temperature experienced by Parabuthus villosus
      (Buthidae), a scorpion found on the gravel plains around Gobabeb, Namibia, and by
      Opisthophthalmus flavescens (Scorpionidae), a dune-dwelling species from the same
      area, were measured under similar field conditions. Thermocouples implanted under
      the segments of the mesosoma measured maximum temperatures as high as 43 degrees
      C in the shade. Air temperatures reached a maximum of 33 degrees C during the
      daytime and a minimum of 12 degrees C at night. Very low metabolic rates compared
      with those of other nonsedentary invertebrates were recorded in both species;
      oxygen consumption ranged from 8 microL g-1 h-1 at 16 degrees C to 115 microL g-1
      h-1 at 40 degrees C. A pulsed Doppler system was used to measure heart rate in
      situ in free-moving scorpions. At night, heart rate declined to about 4 beats min
      1 in resting undisturbed scorpions. During daylight excursions and while
      scorpions hunted for food, heart rates as high as 180 beats min-1 were observed.
      Heart rate was linearly correlated with temperature in P. villosus, with a slope
      of 2.37 (Q10 = 2.18), but in O. flavescens only a limited correlation was
      observed, with a slope of 1.18 (Q10 = 1.69). In O. flavescens, heart rate showed
      hysteresis as body temperature rose during daylight and then decreased during the
      late afternoon and evening; the reverse was observed in P. villosus. In both
      species, haemocyanin-oxygen affinity was independent of temperature, with a
      higher oxygen affinity and a larger pH sensitivity in O. flavescens. The Q10's of
      oxygen consumption and heart rate are quite different in O. flavescens but not as
      different in P. villosus. Although changes in the cardiovascular system, such as
      stroke volume, may also play a role in meeting increased oxygen demand, the
      features of the haemocyanin oxygen transport system, such as the absence of
      temperature sensitivity and a marked pH sensitivity, can also influence the
      maintenance of VO2 under temperature stress. The differences in the normal
      thermal habitats of the two species may be used to explain the distinctions
      between the evolved physiological responses to temperature increase shown by the
      two species.

PMID- 9231399
TI  - Crustacean endocrinology: a retrospective, prospective, and introspective
      analysis.
AB  - From the first discovery of a hormone in a crustacean in the 1920s until the
      present, the field of crustacean endocrinology has undergone, as do many
      crustaceans during their development, a marked metamorphosis. The field has moved
      from the classical era of endocrinological techniques, such as extirpation and
      additive methods, to the modern era of sophisticated biochemistry and molecular
      biology. As new investigatory techniques have been devised, crustacean
      endocrinologists have quickly adopted them and, as a consequence, have made major
      advances. Nevertheless, there is still much room (and need) for the older
      techniques, particularly because there is still a vast gap in our knowledge of
      the endocrine mechanisms of the less highly evolved crustaceans. The bulk of the
      information we have about crustacean endocrinology has been derived from studies
      of decapods. Crustacean endocrinology not only provides information about the
      basic biology of this important group of organisms but also has the potential of
      greatly enhancing our ability to culture species used as food sources for humans.

PMID- 9231400
TI  - Effects of tannins on digestion and detoxification activity in gray squirrels
      (Sciurus carolinensis).
AB  - Acorn tannins may affect food preferences and foraging strategies of squirrels
      through effects on acorn palatability and digestibility and squirrel physiology.
      Captive eastern gray squirrels (Sciurus carolinensis) were fed 100% red oak
      (Quercus rubra) or white oak (Quercus alba) acorn diets to determine effects on
      intake, digestion, and detoxification activity. Red oak acorns had higher phenol
      and tannin levels, which may explain the lower dry matter intakes and apparent
      protein digestibilities and the higher glucuronidation activities observed in
      squirrels. Although the white oak acorn diet had lower apparent protein
      digestibilities than the reference diet, it did not suppress dry matter intake
      for a prolonged period or stimulate glucuronidation. Negative physiological
      effects of a 100% red oak acorn diet suggest gray squirrels may require other
      foods to dilute tannin intake and provide additional nutrients. To distinguish
      the roles of different tannin types in the observed effects of acorn diets on
      squirrels, squirrels were fed rat chow containing no tannins, 4% or 8% tannic
      acid (hydrolyzable tannin), or 3% or 6% quebracho (condensed tannin). Apparent
      protein digestibilities were reduced by tannic acid and quebracho diets. Only the
      8% tannic acid diet tended to increase glucuronidation. Specific effects of
      tannins may largely depend on tannin type, composition, and source and on other
      nutritional and physiological factors.

PMID- 9231401
TI  - The ratio of amount of haemoglobin to total surface area of erythrocytes in birds
      in relation to body mass, age of nestlings, and season of the year.
AB  - The research examined differences in haemoglobin concentration (g%), number of
      erythrocytes (mm-3), length and width of red blood cells (micron), and
      haematocrit value (%) in adult birds of 21 species with body mass ranging from 8
      to 170 g, in eight species of altricial birds during the course of their
      development and in two species throughout the seasons of the year. Erythrocyte
      total surface area was taken to be the product of the surface area of a single
      red blood cell and the erythrocyte count, and the ratio of haemoglobin to the
      total surface area of erythrocytes was then determined. Erythrocyte total surface
      area scaled with haemoglobin concentration in all three of the above situations,
      with the result that the ratio of haemoglobin to total surface area of
      erythrocytes was constant at a mean of 0.53 +/- 0.11 pg micron-2. Changes in the
      total surface area of erythrocytes occur as a consequence of simultaneous changes
      in the size and number of erythrocytes, with haematocrit values remaining
      relatively constant. The constant value of the ratio of haemoglobin to total
      surface area of erythrocytes may be optimal for haemoglobin saturation with
      oxygen in the lungs of birds.

PMID- 9231402
TI  - Renal glomerular and tubular effects of antidiuretic hormone and two antidiuretic
      hormone analogues in house sparrows (Passer domesticus).
AB  - We infused arginine vasotocin, the natural avian antidiuretic hormone, and two
      antidiuretic hormone analogues into house sparrows (Passer domesticus) to
      evaluate the vascular and tubular components of antidiuresis in a small (25-g)
      bird. During control infusion of 25 mmol L-1 NaCl (0.6 mL h-1), urine flow rate
      was 0.73 mL h-1, glomerular filtration rate was 10.0 mL h-1, the ratio of
      polyethylene glycol (PEG) in the urine relative to that in the plasma was 16.4,
      and urine osmolality was 279 mOsmol kg-1. Infusion of arginine vasotocin (0.4 ng
      kg-1 min-1) decreased urine flow rate by 50% and glomerular filtration rate by
      27%, while urine osmolality and the ratio of urine PEG to plasma PEG rose to 150%
      and 140% of control values, respectively. A higher dose of arginine vasotocin
      (1.6 ng kg-1 min-1) accentuated these changes. Infusion of the antidiuretic
      hormone analogue dPTyr(Me)AVT, designed as an antagonist to the V1 (mammalian
      vascular) receptors for arginine vasopressin, by itself (4.0 ng kg-1 min-1) had
      no effect on any measured variable (P > or = 0.1). Infusion of the analogue along
      with arginine vasotocin (0.4 ng kg-1 min-1) abolished the effect of arginine
      vasotocin on glomerular filtration rate, which suggests that this analogue
      blocked vascular receptors for arginine vasotocin in house sparrows. Under these
      circumstances, changes in urine flow rate, the ratio of urine PEG to plasma PEG,
      and urine osmolality were reduced to nonsignificance. The analogue d(CH2)5[D
      Ile2,Ile4,Ala-MH2]AVP, designed as an antagonist to the effects of arginine
      vasopressin at V2 (mammalian renal tubular) receptors, also was without effect by
      itself. However, in the presence of this analogue, the effects of arginine
      vasotocin on urine flow rate and the ratio of urine PEG to plasma PEG were
      significantly enhanced, and this occurred without any enhanced diminution of
      glomerular filtration rate. Thus, this analogue appeared to activate a tubular
      mechanism of antidiuresis. Overall, the data suggest that action of arginine
      vasotocin at renal vascular receptors plays an important role in effecting
      antidiuresis in house sparrows. Blockade of renal vascular actions of arginine
      vasotocin by a V1 antagonist suggest that these receptors may be similar to the
      mammalian vascular (V1) receptor. The data also suggest a separate action of
      arginine vasotocin at the renal tubules, but the receptors there apparently
      differ from the mammalian tubular (V2) receptor.

PMID- 9231403
TI  - The thermal biology of digestion in rubber boas (Charina bottae): physiology,
      behavior, and environmental constraints.
AB  - Coadaptation predicts a match between the thermal physiology and thermoregulatory
      behavior of reptiles. We tested this prediction by studying the digestive biology
      of rubber boas (Charina bottae). We measured the thermal dependence of gastric
      digestive rate and passage rate in rubber boas from 10 degrees C to 35 degrees C.
      We examined the effect of digestion on their thermal preference by measuring the
      temperatures of C. bottae in a thermal gradient before and after feeding. While
      the passage rates calculated from the body temperatures of digesting snakes were
      higher than the passage rates calculated from the body temperatures of
      nondigesting snakes, there was no difference in calculated digestive rates. These
      results indicate that the thermoregulatory behavior of C. bottae may be more
      tightly correlated with factors affecting passage rate than with digestive rate
      alone. Results of simulating the constraints of the thermal environment on the
      digestive biology of C. bottae showed that digestion would take more than twice
      as long in the spring as in the summer. In addition, during the summer, snakes
      thermoregulating as digesting snakes would pass food 12% faster than those
      thermoregulating as nondigesting snakes. These results demonstrate how
      interpretation of laboratory studies can be improved when combined with
      measurements of appropriate environmental conditions.

PMID- 9231404
TI  - Osmotic balance in the eggs of the turtle Chelodina rugosa during developmental
      arrest under water.
AB  - The tropical Australian turtle Chelodina rugosa normally lays its hard-shelled
      eggs in mud, under shallow freshwater, during the monsoon season. The eggs
      undergo developmental arrest until the water recedes and oxygen is able to
      diffuse into the embryo. This period of arrest can exceed 12 wk without embryonic
      mortality. To understand how the eggs avoid osmotic absorption of water leading
      to shell rupture and embryonic death, this study investigates the solute
      concentrations and volumes of the albumen and yolk compartments during
      submergence in distilled water. The albumen loses considerable sodium through the
      shell, particularly during the first week, and its osmotic concentration drops
      from 234 mmol/kg at laying to about 23 mmol/kg. Meanwhile, water from the albumen
      slowly moves through the vitelline membrane into the yolk compartment, which
      enlarges at a constant rate until it approaches the inside of the shell at about
      22 wk. Osmotic uptake dilutes yolk solutes, decreasing the osmotic concentration
      from 281 mmol/kg at laying to 132 mmol/kg at 157 d. Loss of embryonic viability
      is associated with contact of the vitelline membrane with the inside of the
      shell. The principal adaptation of this species for protracted developmental
      arrest under water is a vitelline membrane of such low permeability to water that
      the expansion of the yolk compartment occurs about 10 times more slowly than in
      other chelonians.

PMID- 9231405
TI  - Standard and maximal metabolic rates of goannas (Squamata:Varanidae)
AB  - Standard metabolic rate and maximal metabolic rate during forced exercise are
      examined for nine species of goanna (genus Varanus), with body mass varying from
      10 to 3,750 g. At 35 degrees C, the common pooled mass exponent for standard
      metabolic rate is 0.97 and at 25 degrees C it is 0.89, with considerable
      variation between species (0.43-1.20). Standard metabolic rate at 35 degrees C
      scales interspecifically with body mass0.92 and at 25 degrees C with body
      mass0.87. The Q10 for standard metabolic rate is approximately 2.5 between 25
      degrees and 35 degrees C. At 35 degrees C, maximal metabolic rate scales
      intraspecifically with body mass0.79 and scales interspecifically with body
      mass0.72. Factorial metabolic scope ranges from nine for the larger species to 35
      for the smaller species; it scales with body mass-0.199 at 35 degrees C. The
      maximal metabolic rate of 6.36 mL O2 g-1 h-1 for Varanus caudolineatus is the
      highest recorded for any squamate. Variations from the interspecific regression
      line appear to have some ecological significance. Varanus tristis (a widely
      foraging arboreal goanna) and Varanus eremius (a widely foraging terrestrial
      goanna) have a higher standard metabolic rate than Varanus acanthurus (a
      sedentary terrestrial goanna). The three arboreal goannas (Varanus caudolineatus,
      Varanus gilleni, and Varanus tristis) have a higher maximal metabolic rate than
      the terrestrial species (Varanus brevicauda, V. eremius, V. acanthurus, Varanus
      gouldii, Varanus rosenbergi, and Varanus panoptes).

PMID- 9231406
TI  - Dynamics of brown fat thermogenesis in week-old rats: evidence of relative
      stability during moderate cold exposure.
AB  - Neonates of many mammalian species, including humans, depend primarily on
      thermogenesis by brown adipose tissue as a defense against cold challenge.
      Although the steady-state thermogenic responses of brown adipose tissue to
      various air temperatures are well known, the dynamic responses have received
      relatively little attention. In this article, we examine the relative stability
      of brown adipose tissue thermogenesis during brief perturbations of air
      temperature. Specifically, week-old rats were allowed to settle at one of two
      levels of cold exposure. These two levels were defined on the basis of previous
      work as being moderate (30.5 degrees C) or extreme (23 degrees C). After pups had
      settled at these temperatures, they were exposed to positive or negative air
      temperature perturbations of approximately 3.7 degrees C. Pups experiencing
      perturbations from the moderate air temperature, unlike those exposed to the
      extreme air temperature, exhibited organized thermogenic responses that allowed
      them to return quickly to their preperturbation conditions. These data suggest
      that brown adipose tissue thermogenesis is more stably controlled than has
      previously been suspected.

PMID- 9231407
TI  - Daily torpor and energy expenditure in Sminthopsis macroura: interactions between
      food and water availability and temperature.
AB  - Endothermy allows maintenance of a constant internal thermal milieu for optimal
      physiological functions but results in high energy expenditure and water loss.
      Since torpor can reduce both expenditure of energy and loss of water and thus
      reduces food and water requirements, we determined how different food and water
      regimes affect torpor occurrence and patterns in the dasyurid marsupial
      Sminthopsis macroura at ambient temperatures of 18 degrees C (well below the
      thermoneutral zone) and 28 degrees C (close to the thermoneutral zone). At 18
      degrees C, torpor was more frequent and more pronounced than at 28 degrees C.
      Withdrawal of food reduced the average daily metabolic rate by 20%; withdrawal of
      water alone had little effect. The average daily metabolic rate of individuals
      displaying torpor was 20% lower than that of individuals remaining normothermic.
      At 28 degrees C, the average daily metabolic rate under food restriction was 85%
      of that with food available ad lib. However, this reduction of average daily
      metabolic rate at 28 degrees C seems due not to the use of torpor but mainly to a
      reduction of the resting metabolic rate. The results suggest that at low
      temperature, torpor is used to adjust energy expenditure to availability of food,
      whereas at high temperature, reductions of resting metabolic rate are employed.

PMID- 9231408
TI  - The effects of plant and tooth structure on intake and digestibility in two small
      mammalian herbivores.
AB  - We investigated the interaction between plant structure and animal tooth
      structure and how it can affect digestive performance in two small mammalian
      herbivores. Mastacomys fuscus, an exclusively herbivorous rodent, and Rattus
      lutreolus, a less herbivorous rodent, were fed diets varying in fibre structure
      and level (18%-45% neutral detergent fibre). On high-fibre whole wheat diets, R.
      lutreolus was not able to maintain body mass. M. fuscus was able to maintain body
      mass, and this was related to a much greater intake by M. fuscus on this diet. We
      attribute this result to more effective physical processing by M. fuscus as a
      consequence of a highly developed dentition. On a milled-wheat diet, intake by R.
      lutreolus increased significantly compared with the whole wheat diet, although
      intake was still not great enough to maintain body mass. On diets that were lower
      in fibre than the wheat diet, and with different fibre arrangements, R. lutreolus
      was able to achieve intakes great enough to maintain body mass. This suggests
      that, in addition to gut constraints, the physical form of the plant diet and
      dental structure can have a significant effect on digestive performance by
      animals in feeding trials.

PMID- 9231410
TI  - Basal metabolic rate in relation to body composition and daily energy expenditure
      in the field vole, Microtus agrestis.
AB  - Basal metabolic rate in the field vole (Microtus agrestis) was studied in
      relation to body composition and daily energy expenditure in the field. Daily
      energy expenditure was measured by means of doubly labelled water (D2 18O). In
      the same individuals, basal metabolic rate was subsequently derived from O2
      consumption in an open-circuit system in the laboratory. Body composition was
      obtained by dissecting the animals and determining fresh, dry, and lean dry mass
      of different organs. Daily energy expenditure for free-living field voles ranged
      from 1.8 to 4.5 times basal metabolic rate, with an average of 2.9 times basal
      metabolic rate. Variation in both daily energy expenditure and basal metabolic
      rate was best explained by body mass. Gender or reproductive activity did not
      have significant additive effects. Daily energy expenditure and basal metabolic
      rate showed significant positive relationships to body mass with similar mass
      exponents of 0.493 and 0.526, respectively. Overall, there was a significant
      correlation between daily energy expenditure and basal metabolic rate, but the
      mass-independent residuals (deviations from the allometrically predicted values)
      did not correlate. Carcass analysis revealed that a number of organs were
      slightly better predictors for daily energy expenditure and basal metabolic rate
      than was fresh body mass. Mass-independent residuals of lean dry heart mass and
      basal metabolic rate were positively correlated, which is in agreement with the
      idea that basal metabolic rate reflects the size of metabolically active organs.
      The study does not provide support for an intraindividual association of basal
      metabolic rate with daily energy expenditure in the field.

PMID- 9231409
TI  - Effects of thyroid status on cold-adaptive thermogenesis in Brandt's vole,
      Microtus brandti.
AB  - Hyper- and hypothyroidism were induced by subcutaneous injection of thyroxine and
      by oral administration of methimazol in Brandt's voles. The effects of the two
      treatments on metabolic thermogenesis at 25 degrees C and 4 degrees C were
      investigated. The level of resting metabolic rate was closely related to thyroid
      status: high in the hyperthyroid case and low in the hypothyroid case. However,
      no increase in resting metabolic rate occurred in either case during further cold
      acclimation. Hyperthyroidism resulted in an increased nonshivering thermogenesis,
      which was much enhanced by lower temperature, but hypothyroidism led to a
      suppressed nonshivering thermogenesis in the cold. The state-4 and state-3
      respirations and the activities of cytochrome-c oxidase of liver mitochondria
      were elevated in hyperthyroid animals but attenuated in hypothyroid ones.
      However, these levels were scarcely changed after further cold acclimation. Both
      hyperthyroidism and cold acclimation induced the recruitment of brown adipose
      tissue, but brown adipose tissue was different biochemically in the two cases: in
      hyperthyroidism, the total protein was reduced, while fat content increased; in
      cold acclimation, the total and mitochondrial proteins were increased. However,
      in hypothyroid voles, the normal adaptive changes in brown adipose tissue were
      impaired in further cold acclimation. The activity of cytochromec oxidase in
      brown adipose tissue was increased by hyperthyroidism and enhanced in further
      cold. In contrast, its activity was inhibited in hypothyroid animals, though
      activated to some extent in cold. These results demonstrate that normal thyroid
      function is essential for the cold-induced increase of resting metabolic rate and
      nonshivering thermogenesis and that there is a synergism between thyroid hormone
      and cold acclimation in the regulation of nonshivering thermogenesis in Brandt's
      vole. In addition, the blunted response of brown adipocytes to the cold may be
      the cytological mechanism for the suppressed nonshivering thermogenesis found
      with hypothyroidism.

PMID- 9231411
TI  - A test for passive absorption of glucose in yellow-rumped warblers and its
      ecological implications.
AB  - In an earlier study, we found that yellow-rumped warblers had in vitro active
      uptake rates of D-glucose that were only a few percent of the glucose absorption
      rate achieved at the whole-animal level. Here we used a pharmacokinetic technique
      to test whether a substantial amount of sugar can be absorbed passively. We used
      yellow-rumped warblers (Dendroica coronata), known for their seasonal frugivory,
      freely feeding on a synthetic mash formulated with naturally occurring
      concentrations of D-glucose. Birds absorbed 89.8% +/- 1.0% (SE) of the D-glucose
      in the mash. When fed the same mash with trace-labeled 3H L-glucose, the
      stereoisomer that does not interact with the intestinal Na(+)-glucose
      cotransporter, 3H appeared in plasma, an indication that this stereoisomer of
      glucose was absorbed. We used 3H levels in plasma and excreta in a
      pharmacokinetic model to calculate L-glucose extraction efficiency (i.e., the
      percent absorbed). Calculated mean extraction efficiency for the passively
      absorbed L-glucose averaged 91% +/- 23%. Our finding of considerable passive
      absorption reconciles the in vitro and in vivo results for D-glucose absorption
      and is in concert with results from five other avian species. The passive pathway
      appears to provide birds with an absorptive process that can respond quickly to
      changing luminal concentration and that is energetically inexpensive to maintain
      and modulate in real time but that may bear a cost. Less discriminate passive
      absorption might increase vulnerability to toxins and thus constrain foraging
      behavior and limit the breadth of the dietary niche.

PMID- 9231412
TI  - Regulation of nitrogen fixation in Azospirillum brasilense.
AB  - The regulation of nitrogen fixation in Azospirillum brasilense is very
      complicated, and it responds to exogenous fixed nitrogen or a change of oxygen
      concentration. This regulation occurs at both transcriptional and
      posttranslational levels. Unlike regulation seen in Klebsiella pneumoniae,
      transcription of nifA does not require NTRB/NTRC in A. brasilense and the
      expression of nifHDK is controlled by posttranslational regulation of NIFA
      activity. Addition of NH4+ or a shift from microaerobic to anaerobic conditions
      also causes a rapid loss of nitrogenase activity in A. brasilense. This
      posttranslational regulation of nitrogenase activity involves the DRAT/DRAG
      regulatory system, which is similar to that of Rhodospirillum rubrum. Both DRAT
      and DRAG activities are regulated in vivo, but the mechanisms for their
      regulation are unknown.

PMID- 9231413
TI  - A flagellar-specific ATPase (FliI) is necessary for flagellar export in
      Helicobacter pylori.
AB  - Although flagellar motility is essential for the colonisation of the stomach by
      Helicobacter pylori, little is known about the regulation of flagellar
      biosynthesis in this organism. We have identified a gene in H. pylori, designated
      fliI, whose deduced amino acid sequence revealed extensive homology with the
      FliI/LcrB/InvC family of proteins which energise the export of flagellar and
      other virulence factors in several bacterial species. An isogenic mutant of fliI
      was non-motile and synthesised reduced amounts of flagellin and hook protein
      subunits. The majority (> 99%) of mutant cells were completely aflagellate. These
      results suggest that FliI is a novel ATPase involved in flagellar export in H.
      pylori.

PMID- 9231414
TI  - Histidine-44 of the A subunit of Escherichia coli enterotoxin is involved in its
      enzymatic and biological activities.
AB  - We examined the role in toxicity of histidine-44 of the A subunit of Escherichia
      coli enterotoxin, which is located in the active site cavity close to glutamic
      acid-112. Although amino acid substitution of histidine-44 usually renders a
      mutant toxin unstable to trypsin, one mutant, alanine-44 (His44Ala) was found to
      be stable. His44Ala did not show any agmatine:ADP-ribosyltransferase activity in
      the presence or absence of recombinant ADP-ribosylation factor. It showed no
      diarrheal or rabbit skin permeability activity and was a competitor in
      enterotoxin-ADP-ribosyltransferase assays containing recombinant ADP-ribosylation
      factor. These results suggest that like glutamic acid-112, histidine-44 plays an
      essential role in toxicity. A tentative model, which explains NAD+ catalysis and
      the transfer of the ADP-ribosyl moiety to a target amino acid, is proposed for
      histidine-44 and glutamic acid-112.

PMID- 9231415
TI  - Amended structure of side chains in a cell wall mannan from Candida albicans
      serotype A strain grown in yeast extract-Sabouraud liquid medium under acidic
      conditions: detection of the branched side chains corresponding to antigenic
      factor 4.
AB  - In a previous study, we reported the excess production of alpha-1,3-linked
      mannose residues with the complete disappearance of beta-1,2-linked mannose
      residues in cell wall mannans of Candida albicans serotype A strain cells, which
      were grown in yeast extract-Sabouraud liquid medium at pH 2.0. In the present
      study, we examined the immunochemical reactivity of the same mannan of NIH A-207
      with an enzyme-linked immunosorbent assay (ELISA) using several antisera to
      antigenic factors of the genus Candida (FAbs) and the structure of the mannan by
      two-dimensional homonuclear Hartmann-Hahn analysis. The ELISA showed that the
      mannan reacts to FAb 4 but not to FAbs 13b and 34, which are reported to be
      antibody factors against linear side chains containing an alpha-1,3-linked
      mannose residue. In the Hartmann-Hahn analysis, we found two branched side
      chains, Man alpha 1-2Man alpha 1-3[Man alpha 1-6]Man alpha 1-(2Man alpha 1
      )(2)2Man and Man alpha 1-3[Man alpha 1-6]Man alpha 1-(2Man alpha 1-)(2)2Man,
      instead of the previously reported linear side chains. The branched side chains
      are oversynthesized under acidic conditions.

PMID- 9231416
TI  - Localization of germination-specific spore-lytic enzymes in Clostridium
      perfringens S40 spores detected by immunoelectron microscopy.
AB  - The localization of germination-specific spore-lytic enzymes, an amidase and a
      muramidase, in Clostridium perfringens S40 spores was examined by immunoelectron
      microscopy with respective antisera raised against the enzymes and a colloidal
      gold-immunoglobulin G complex. For both antisera, immunogold particles were
      visualized on the outside of the cortex of dormant spores, and they were not
      detected in germinated spores and decoated spores.

PMID- 9231417
TI  - Radiation-induced chromosomal rearrangement as an aid to analysis of the genetic
      constitution of Phaffia rhodozyma.
AB  - Electrophoretic karyotypes of 80 auxotrophic and morphological mutants obtained
      from two Phaffia rhodozyma strains (ATCC 24203 and ATCC 24229) by gamma-radiation
      were investigated. Contour-clamped homogeneous gel electrophoresis separation of
      the chromosomal size DNAs revealed 29 new chromosomal patterns after mutagen
      treatment. No correlation was found between a given type of chromosomal
      aberration and any phenotypic character. However, analysis of the chromosomal
      rearrangements proved to be useful for a more exact determination of chromosome
      number and genome size. The total genome size of ATCC 24229 was found to be 19.3
      Mb, with nine chromosomes, while analysis of the mutant derivatives of ATCC 24203
      suggested the presence of 11 chromosomes, with an estimated total genome size of
      22.2 Mb. The advantages of the analysis of mutant electrophoretic karyotypes for
      genome characterization are discussed.

PMID- 9231418
TI  - A plasmid-mediated CMY-2 beta-lactamase from an Algerian clinical isolate of
      Salmonella senftenberg.
AB  - Multiresistance to antibiotics including beta-lactams, e.g. cefoxitin, was
      transferred by conjugation to Escherichia coli strain C1a from a clinical isolate
      of Salmonella senftenberg recovered from stools of an Algerian child. The
      susceptibility pattern to beta-lactams was similar to the profile mediated by an
      AmpC-type beta-lactamase. By biochemical analysis, typical AmpC-type enzyme
      substrate and inhibition profiles were obtained. Finally, an ampC plasmid-encoded
      beta-lactamase gene was cloned and sequenced. Its deduced amino acid sequence
      confirmed its identity as a class C beta-lactamase. It showed 99.5% sequence
      identity with the plasmid-mediated beta-lactamase CMY-2. The differences in the
      amino acid sequences of the two enzymes were located in the signal peptide.

PMID- 9231419
TI  - On the unidirectionality of arginine uptake in the yeast Saccharomyces
      cerevisiae.
AB  - The reversibility of arginine accumulation was followed in exponentially growing
      cells of Saccharomyces cerevisiae and in the same cells transferred to non
      growing energized conditions. Under non-growing conditions the accumulated
      arginine is retained in the cells while in exponentially growing cells the
      accumulated radioactivity is released after the addition of high external
      concentrations of arginine. There are indications that the process is saturable.
      The accumulated arginine is not exchanged for other related amino acids (L
      citrulline, L-histidine). Only L-lysine (a low-affinity substrate of the specific
      arginine permease) provokes partial radioactivity efflux from the cells. The
      switch of the arginine-related radioactive label efflux to its complete retention
      in the cells after changing the growth conditions occurs within a few minutes and
      is tentatively attributed to two concomitantly occurring events: (1) the actual
      presence of radioactive arginine (not its metabolite(s)) in the cell and (2) a
      modification of the specific arginine permease. The specific exchange of arginine
      described in the present study contrasts with the currently widely accepted
      opinion of unidirectionality of amino acid fluxes in yeast. The reasons why this
      phenomenon has not been observed before are discussed.

PMID- 9231420
TI  - Neuraminidase (sialidase) activity of Haemophilus parasuis.
AB  - Neuraminidase (sialidase), a potential virulence factor in bacteria, was
      demonstrated in Haemophilus parasuis, an invasive swine pathogen, but not in four
      other pathogens of the Pasteurellaceae family: H. influenzae, H. somnus, H.
      paragallinarum, or Actinobacillus pleuropneumoniae. H. parasuis neuraminidase had
      an acidic pH optimum and a specificity for several substrates also cleaved by
      other bacterial neuraminidases. Similar to the neuraminidase of Pasteurella
      multocida, H. parasuis neuraminidase was cell associated and did not require
      divalent cations for activity. Exogenous sialic acid added to growth medium of H.
      parasuis was cleared after a lag of about 10 h and these cultures grew to a
      greater final density than cultures without added sialic acid, indicating that
      exogenous sialic acid is metabolized. The role of sialidase in providing
      nutrients to H. parasuis may be an important factor in its obligate parasitism.

PMID- 9231421
TI  - OHIO-1 beta-lactamase mutants: Asp179Gly mutation confers resistance to
      ceftazidime.
AB  - The Asp179Gly mutant of the OHIO-1 beta-lactamase, an SHV enzyme, was constructed
      to investigate the effect of disruption of the omega loop on beta-lactamase
      activity in this class A enzyme. In Escherichia coli DH5 alpha the strain
      possessing the Asp179Gly mutation of the OHIO-1 beta-lactamase demonstrated
      increased susceptibility to all beta-lactams except ceftazidime and ceftriaxone.
      The minimum inhibitory concentrations for ceftazidime and ceftriaxone increased
      from 0.25 and 0.015 microgram/ml to 4.0 and .25 micrograms/ ml respectively. For
      ceftazidime, a substrate not hydrolyzed by the wild-type enzyme (K(m) > or = 500
      microM), the K(m) of the Asp179Gly mutant beta-lactamase was measured to be 7
      microM and the Vmax was 0.13 microM/min. The minimum inhibitory concentrations,
      K(m), and Vmax for all other beta-lactams decreased. Our analysis of this OHIO-1
      beta-lactamase mutant suggests that disruption of the salt bridge in the omega
      loop by substitution of a glycine at position 179 markedly decreases the
      catalytic efficiency of the enzyme.

PMID- 9231422
TI  - Microbial flora in the deepest sea mud of the Mariana Trench.
AB  - In an attempt to characterize the microbial flora on the deepest sea floor, we
      isolated thousands of microbes from a mud sample collected from the Mariana
      Trench. The microbial flora found at a depth of 10897 m was composed of
      actinomycetes, fungi, non-extremophilic bacteria, and various extremophilic
      bacteria such as alkaliphiles, thermophiles, and psychrophiles. Phylogenetic
      analysis of Mariana isolates based on 16S rDNA sequences revealed that a wide
      range of taxa were represented.

PMID- 9231423
TI  - Mutants of Saccharomyces cerevisiae defective in vacuolar function confirm a role
      for the vacuole in toxic metal ion detoxification.
AB  - To directly define vacuolar role(s) in metal detoxification, we have examined the
      responses of vacuole-deficient mutants of Saccharomyces cerevisiae to several
      potentially toxic metals known to be mainly detoxified in the cytosol (Cu, Cd) or
      the vacuole (Co, Mn, Ni, Zn). Three mutants, deficient in targeting of vacuolar
      proteins, were used with JSR18 delta 1 being devoid of any vacuole-like structure
      while ScVatB and ScVatC were deficient in specific protein subunits of the V
      ATPase. The results obtained show that the absence of a vacuole or a functional
      vacuolar H(+)-ATPase was associated with increased sensitivity and a largely
      decreased capacity of the vacuole-deficient strains to accumulate Zn, Mn, Co and
      Ni, confirming an essential role for the vacuole in detoxification of these
      metals. In addition, the lack of vacuolar involvement in detoxification of Cu and
      Cd was confirmed since these metals did not exhibit increased toxicity towards
      the vacuolar mutants nor were there significant differences in Cu or Cd
      accumulation between parental and mutant strains.

PMID- 9231425
TI  - Low-temperature-induced desaturation of fatty acids and expression of desaturase
      genes in the cyanobacterium Synechococcus sp. PCC 7002.
AB  - Changes in response to temperature of lipid classes, fatty acid composition and
      mRNA levels for acyl-lipid desaturase genes were studied in the marine
      unicellular cyanobacterium, Synechococcus sp. PCC 7002. The degree of
      unsaturation of C18 fatty acids increased in cells grown at lower temperature for
      all lipid classes, and omega 3 desaturation occurred specifically in cells grown
      at low temperature. While the level of 18:1(9) fatty acids declined, desaturation
      at the omega 3 position of C18 fatty acids increased gradually during a 12-h
      period after a temperature shift-down to 22 degrees C. However, the mRNA levels
      of the desA (delta 12 desaturase), desB (omega 3 desaturase) and desC (delta 9
      desaturase) genes increased within 15 min after a temperature shift-down to 22
      degrees C; the desaturase gene mRNA levels also rapidly declined within 15 min
      after a temperature shift-up to 38 degrees C. Therefore, the elevation of mRNA
      levels for the desaturase genes is not the rate-limiting event for the increased
      desaturation of membrane lipids after a temperature shift-down. The rapid, low
      temperature-induced changes in mRNA levels occurred even when cells were grown
      under light-limiting conditions for which the growth rates at 22 degrees C and 38
      degrees C were identical. These studies indicate that the ambient growth
      temperature, and not some other growth rate-related process, regulates the
      expression of acyl lipid desaturation in this cyanobacterium.

PMID- 9231424
TI  - Expression of P, S, and F1C adhesins by cytotoxic necrotizing factor 1-producing
      Escherichia coli from septicemic and diarrheic pigs.
AB  - Nineteen papC-positive cytotoxic necrotizing factor 1 (CNF1)-producing
      Escherichia coli isolates from pigs with septicemia or diarrhea were tested for
      the presence of pap-, sfa-, and afa-related sequences encoding P/Prs, S/F1C, and
      Dr/AFA adhesins respectively. Production of adhesins by isolates was tested by
      mannose-resistant hemagglutination (MRHA), sialidase treatment of erythrocytes
      and particle agglutination tests. Production of P, S, and F1C fimbriae by
      isolates was also examined by immunofluorescence. All isolates were pap+ by PCR.
      Eighteen isolates (95%) were MRHA for ovine and human A erythrocytes and
      exhibited GalNac-GalNac receptor specificity associated with class III P(Prs)
      adhesins. Fifteen (79%) of the 19 isolates reacted with antisera specific for one
      or more different P fimbrial serotypes on immunofluorescence. Three of these
      isolates also demonstrated Gal-Gal receptor specificity associated with class I
      or II P fimbrial adhesins. Fifteen (79%) of the isolates were sfa+ by PCR. Seven
      of these isolates exhibited sialidase-sensitive MRHA of bovine and human O
      erythrocytes and reacted with serum specific for S fimbriae on
      immunofluorescence. Seven of the 8 sfa+ isolates which were MRHA-negative for
      bovine erythrocytes reacted with serum specific for F1C fimbriae on
      immunofluorescence. All isolates produced type 1 fimbriae as determined by
      mannose-sensitive agglutination of yeast cells. None of the isolates were afa+ by
      PCR or colony hybridization. Results suggest that most pap+ porcine CNF1
      producing E. coli isolates express P fimbriae bearing class III (Prs) type
      adhesins. In addition, most of these isolates also produce S or F1C fimbriae.

PMID- 9231426
TI  - Purification and characterization of a GroEL homologue from the moderately
      eubacterial halophile Pseudomonas sp. #43.
AB  - We have purified to apparent homogeneity and characterized a molecular chaperonin
      GroEL homologue (hpGroEL) from a moderately halophilic eubacterium, Pseudomonas
      sp. #43. Although this halophilic bacterium requires 1-2 M NaCl for growth,
      hpGroEL did not require a high concentration of salt for its stability, ATPase
      activity and refold-promoting activity for denatured protein. The ATPase activity
      was even more halo-sensitive than that of GroEL from Escherichia coli. The
      hpGroEL protein promotes Mg(2+)-ATP-dependent refolding of urea-denatured alpha
      glucosidase in the presence of E. coli-GroES, indicating that chaperonins 60 and
      10 isolated from halophilic and nonhalophilic eubacteria, respectively, can
      cooperate with each other.

PMID- 9231427
TI  - Regulation of chitin synthase activity in the dimorphic fungus Benjaminiella
      poitrasii by external osmotic pressure.
AB  - The effects of changes in external osmotic pressure on chitin synthase activity
      of a dimorphic fungus, Benjaminiella poitrasii, have been investigated. Mycelial
      and yeast cells incubated in medium of low osmolality (distilled water, 0 mOsm)
      for 10 min had 2-3-fold higher specific activities of native chitin synthase in
      mixed membrane preparations than cells that had been subjected to a high
      osmolality medium (1.2 M sorbitol in distilled water, 1612 mOsm). Cells suspended
      in media of different osmolalities for 10 min were also affected in the extent of
      germ tube formation. Germ tube formation was highest in cells incubated in low
      osmolality medium. The addition of protein phosphatase inhibitors (cyclosporin A,
      1.2 micrograms/ml; cantharidin, 20 microM) abolished the effect of hypo-osmotic
      stress on chitin synthase activation of yeast mixed membrane preparations. The
      presence of protein kinase inhibitors (genistein, 40 micrograms/ml; H-7, 100
      microM) and a Ca2+ channel blocker (verapamil, 50 microM) reduced chitin synthase
      activity to 50-60% of that observed in cells under hypo-osmotic shock. These
      inhibitors also inhibited germ tube formation. This suggests that chitin synthase
      activity and yeast hyphal morphogenesis are both subject to regulation by osmotic
      pressure, phosphorylation and calcium.

PMID- 9231428
TI  - Oral bacteria inhibit Helicobacter pylori growth.
AB  - Various oral bacterial species were found to inhibit the growth of Helicobacter
      pylori strains. The growth inhibitory activities of most of these oral bacteria
      were adversely affected by heating at 80 degrees C for 60 min or by protease
      treatment, indicating that these bacteria produce bacteriocin-like inhibitory
      proteins against H. pylori strains. The antagonistic effects of oral bacteria
      against H. pylori may restrain colonization by this organism in the oral cavity.

PMID- 9231429
TI  - Determination of specific DNA strand discontinuities with nucleotide resolution
      in exponentionally growing bacteria harboring rolling circle-replicating
      plasmids.
AB  - Plasmid replication by the rolling circle mechanism and conjugative transfer of
      plasmids require the generation of a specific strand discontinuity in the DNA. In
      both processes cleavage at the so-called nic site is catalyzed by plasmid-encoded
      proteins. The strand discontinuities at the conjugative origins of transfer of
      plasmid pE194 and pMV158 were determined in Bacillus subtilis and Streptococcus
      pneumoniae, respectively, with a recently developed runoff DNA synthesis assay.
      The positions of intracellular cleavage within the respective transfer origins
      were shown to coincide with the site predicted for pE194 and with the nic site
      determined in vitro for pMV158. For pMV158, the influence of a mutation in the S.
      pneumoniae polA gene on the efficiency of replication was investigated. In
      addition, the nic site within the double-stranded origin of the-rolling circle
      replicating plasmid pMV158 in S. pneumoniae as well as that of pFX2 in
      Escherichia coli was mapped with nucleotide resolution.

PMID- 9231431
TI  - Conjoint and dissociable effects of syntactic and semantic context.
AB  - Manipulating the semantic relatedness of noun and verb targets in contexts where
      they are grammatically appropriate or inappropriate allows for simultaneous
      examination of syntactic and semantic context effects. A lexical-decision
      experiment showed both a syntactic context effect and a semantic relatedness
      effect that was stronger in syntactically appropriate conditions. Thus, latencies
      appeared to be conjointly determined by syntactic and semantic context. In
      contrast, naming experiments also showed both semantic and syntactic effects, but
      the syntactic context effect was independent of semantic relatedness and was
      observed in the virtual absence of sensitivity to semantic anomaly. Thus,
      syntactic and semantic processing are largely dissociable in the naming task. In
      conjunction with other findings in the literature, this suggests the existence of
      an isolable level of syntactic assignment that precedes semantic integration of
      content words in sentence comprehension.

PMID- 9231430
TI  - A PCR-based method to characterise and identify benzimidazole resistance in
      Helminthosporium solani.
AB  - Control of Helminthosporium solani, the cause of silver scurf in potato tubers,
      has been impaired by selection of benzimidazole-resistant strains as a result of
      repeated use of the fungicide thiabendazole. Identification of thiabendazole
      resistant strains of H. solani by conventional techniques takes several weeks.
      Primers designed from conserved regions of the fungal beta-tubulin gene were used
      to PCR amplify and sequence a portion of the gene. A point mutation was detected
      at codon 198 in thiabendazole-resistant isolates causing a change in the amino
      acid sequence from glutamic acid to alanine or glutamine. Species-specific PCR
      primers designed to amplify this region were used in conjunction with a
      restriction endonuclease to cause cleavage in sensitive isolates only and thus
      provide a rapid diagnostic test to differentiate field isolates.

PMID- 9231433
TI  - Effects of orthographic neighborhood in visual word recognition: cross-task
      comparisons.
AB  - Effects of orthographic neighborhood in visual word recognition in Spanish were
      examined in 5 paradigms: progressive demasking, standard lexical decision,
      lexical decision with blocking of neighborhood density, naming, and semantic
      categorization. The results showed inhibitory effects of neighborhood frequency
      in the progressive-demasking task, in both lexical-decision tasks, as well as for
      low-density words in the naming task, and for high-density words in the semantic
      categorization task. Higher levels of neighborhood density produced an inhibitory
      trend in the progressive-demasking task, facilitation in lexical decision
      (significant only when neighborhood density was blocked), and a robust
      facilitation effect in naming (only for words with higher frequency neighbors). A
      global analysis across tasks and one simulation study helped outline some of the
      underlying task-specific and task-independent mechanisms.

PMID- 9231434
TI  - Recollective and automatic uses of memory.
AB  - Three cued-recall experiments examined the effects of learning conditions and set
      size on recollective and automatic uses of memory. Words were studied under
      different conditions and had either small or large preexisting associative sets.
      Results based on the process-dissociation procedure showed that learning
      conditions and set size influenced recollective uses of memory, whereas only set
      size influenced automatic uses. Other results indicated that process-dissociation
      and direct-indirect test procedures produce similar results. The findings suggest
      that the relative contributions of recently acquired information and preexisting
      information depend on how memory is being used. Recollective uses of memory are
      affected by the nature of recent study and by what such study activates in long
      term memory. In contrast, automatic uses of memory are more affected by what the
      test cue automatically activates than by what has been learned during recent
      study.

PMID- 9231435
TI  - Context memory and the selection of frequency estimation strategies.
AB  - When people estimate event frequency, they sometimes retrieve and count event
      instances. This study demonstrates a direct relation between the use of these
      enumeration-based strategies and the contents of memory. In 3 experiments,
      participants studied target-context word pairs, estimated presentation frequency
      for target words, and recalled context words. Study time, target-context
      relatedness, and study-phase instructions were manipulated, producing large
      differences in memory for context words. When context memory was best, estimation
      time increased sharply with presentation frequency, and the steepness of this
      estimation time-presentation frequency function decreased with context memory.
      These results indicate that enumeration was common only when context memory was
      good, that encoding factors determine how frequency is represented, and that the
      contents of memory restrict strategy selection.

PMID- 9231436
TI  - Attenuating verbal overshadowing through color retrieval cues.
AB  - Five experiments showed that interference resulting from verbalizing visual
      stimuli (verbal overshadowing) can be reduced by reintroducing visual cues
      present at encoding. Object color and background color were used as cues.
      Participants learned either easy- or hard-to-name figures and then performed an
      image rotation task. Before performing the imagery task, participants were re
      presented with the color patch associated with each figure. Color re-presentation
      attenuated the impairment associated with easy-to-name stimuli (Experiment 1) as
      well as labeled hard-to-name stimuli (Experiment 2). However, background color
      cues had no effect on imagery performance (Experiment 3). Experiment 4 showed
      that naming the object colors at encoding makes color retrieval cues ineffective.
      Finally, Experiment 5 showed that object color cues can help participants to
      overcome previously exhibited impairment resulting from covert verbalization.

PMID- 9231437
TI  - The role of examples and rules in the acquisition of a cognitive skill.
AB  - In 3 experiments, participants memorized 8 examples, each exemplifying a
      different rule. Participants were asked to extend these rules to new examples.
      They practiced applications of the rules to examples over a period of 4 days
      (Experiment 1) or 5 days (Experiments 2 and 3). Although these rules were
      bidirectional, an asymmetry gradually built up such that participants became more
      facile in using the rules in the practiced direction. Participants also showed an
      advantage when the initial study example was repeated or when test examples were
      repeated. It is argued that skill acquisition involves development of a complex
      set of strategies based on use of rules and retrieval of examples. Four
      overlapping stages of skill acquisition are described.

PMID- 9231438
TI  - What makes an analogy difficult? The effects of order and causal structure on
      analogical mapping.
AB  - In 4 experiments, the author tested 2 factors that affect the difficulty of
      analogies: order of presentation of information and causal structure. Experiments
      1, 2, and 4 showed robust order effects for the positioning of sentences-sentence
      pairs in a variety of mapping problems. Experiments 2, 3, and 4 revealed the
      effects of causal structure in these analogies. Experiment 3 showed that the
      beneficial effects of causal structure are most marked in thematic, mapping
      problems presented in a casual question-answering context. Experiment 4 dealt
      with the interaction between order and causal structure and showed that order
      effects occur only in the presence of causal structure. Of all the analogy models
      in the literature, the incremental analogy machine is the best predictor of these
      results.

PMID- 9231439
TI  - Extrapolation: the sine qua non for abstraction in function learning.
AB  - Abstraction was investigated by examining extrapolation behavior in a function
      learning task. During training, participants associated stimulus and response
      magnitudes (in the form of horizontal bar lengths) that covaried according to a
      linear, exponential, or quadratic function. After training, novel stimulus
      magnitudes were presented as tests of extrapolation and interpolation.
      Participants extrapolated well beyond the range of learned responses, and their
      responses captured the general shape of the assigned functions, with some
      systematic deviations. Notable individual differences were observed, particularly
      in the quadratic condition. The number of unique stimulus-response pairs given
      during training (i.e., density) was also manipulated but did not affect training
      or transfer performance. Two rule-learning models, an associative-learning model,
      and a new hybrid model with associative learning and rule-based responding
      (extrapolation-association model [EXAM]) were evaluated with respect to the
      transfer data. EXAM best approximated the overall pattern of extrapolation
      performance.

PMID- 9231440
TI  - Dissociations of grammaticality and specific similarity effects in artificial
      grammar learning.
AB  - Three artificial grammer learning experiments investigated the memory processes
      underlying classification judgments. In Experiment 1, effects of grammatically,
      specific item similarity, and chunk frequency were analogous between
      classification and recognition tasks. In Experiments 2A and 2B, instructions to
      exclude "old" and "similar" test items, under conditions that limited the role of
      conscious recollection, dissociated grammaticality and similarity effects in
      classification. Dividing attention at test also produced a dissociation in
      Experiment 3. It is concluded that a dual-process model of classification,
      whereby the grammaticality and specific similarity effects are based mostly on
      automatic and intentional memory processes, respectively, is consistent with the
      results, whereas a unitary mechanism account is not. This conclusion is further
      supported by evidence indicating that chunk frequency had both implicit and
      explicit influences on classification judgments.

PMID- 9231441
TI  - Using numerosity judgments to determine what is learned during automatization.
AB  - An important question in learning is the nature of the information required to
      support skilled, or automatic, performance. In 2 experiments, participants
      counted patterns of 8-10 objects displayed on a computer screen for 4 sessions of
      240 trials each before being transferred to a different set of patterns for a
      final session of 240 trials. The patterns in the final session differed from
      those seen in the 4 training sessions in either overall configuration (Experiment
      1) or identity of constituents (Experiment 2). Results indicated that both types
      of information are important in learning and automatization of a counting task
      and support the idea that what is attended to during training will be necessary
      to support subsequent automatic performance.

PMID- 9231442
TI  - A community prevention trial to reduce alcohol-involved accidental injury and
      death: overview.
AB  - The 5-year "Preventing Alcohol Trauma: A Community Trial" project in the United
      States was designed to reduce alcohol-involved injuries and death in three
      experimental communities. The project consisted of five mutually reinforcing
      components: (1) Community Mobilization Component to develop community
      organization and support, (2) Responsible Beverage Service Component to establish
      standards for servers and owner/managers of on-premise alcohol outlets to reduce
      their risk of having intoxicated and/or underage customers in bars and
      restaurants, (3) Drinking and Driving Component to increase local DWI enforcement
      efficiency and to increase the actual and perceived risk that drinking drivers
      would be detected, (4) Underage Drinking Component to reduce retail availability
      of alcohol to minors, and (5) Alcohol Access Component to use local zoning powers
      and other municipal controls of outlet number and density to reduce the
      availability of alcohol. This paper gives an overview of the rationale and causal
      model, the research design and outline of each intervention component for the
      entire prevention trial.

PMID- 9231443
TI  - Community mobilization: evaluation of an environmental approach to local action.
AB  - "Community mobilization" in the Community Trials Project refers to organizing
      community members to support and implement policies to reduce alcohol-involved
      trauma. This paper defines the conceptual model of mobilization used in the
      project. In evaluating the project, we were guided by the conceptual model and we
      used structured materials from interviews with local staff in all three
      experimental communities; we found that the overall goal of mobilization
      (implementation of policies) was achieved. Additional observations based on
      naturalistic case studies of the communities include: (1) the importance of an
      established research base, (2) the varying role and problematic nature of
      coalitions, (3) the strategic advantage of early project support among the
      general population, (4) the role played by key leaders in mobilization, (5) the
      advantages of a multi-component design, and (6) the key role played by media
      advocacy.

PMID- 9231444
TI  - Media advocacy in community prevention: news as a means to advance policy change.
AB  - Media advocacy within the Community Trials Project refers to the strategic use of
      news media to advance a social or public policy initiative. First, this paper
      presents a conceptual model that guided analyses of media advocacy. Secondly, it
      documents increases in alcohol-related news coverage. Thirdly, it compares
      changes in perceived risk of arrest after drinking and driving that can be linked
      to increased DUI news coverage. Fourthly, it examines community awareness of
      enforcement efforts in terms of both media advocacy efforts and traditional
      public information campaigns. Results indicate that: (1) training in media
      advocacy can increase coverage of news events generated by local community
      members including volunteers, (2) increased news coverage can be generated for
      both electronic (television) and print media, (3) increased news coverage did
      focus public attention on specific issues in support of prevention components,
      (4) while there are differential audiences/readers for the print (newspaper) and
      electronic (TV) media, both audiences are affected and (5) media advocacy can be
      more effective than a paid public information campaign in increasing public
      awareness of alcohol issues.

PMID- 9231445
TI  - Drinking and driving prevention in the community: program planning and
      implementation.
AB  - This paper describes the rationale, development and implementation of the
      Drinking and Driving Component, which is one of five components of the Community
      Trials Project conducted by the Prevention Research Center, Berkeley, California
      (USA). It traces the background of drunk driving enforcement technology and
      practice against which the programs at the three sites were implemented. A
      conceptual model for the enforcement component of a comprehensive community
      alcohol-related trauma project is presented and its implementation at the three
      sites is described. Limitations in the available police department resources
      delayed the implementation of local programs. Media advocacy tied to specific
      operations proved to be successful in publicizing sensors and sobriety
      checkpoints were only partially accepted. Overall, the community trials sites
      increased or held steady their arrest rates in contrast to the comparison sites
      where DUI arrests declined.

PMID- 9231446
TI  - The effect of drinking and driving interventions on alcohol-involved traffic
      crashes within a comprehensive community trial.
AB  - The Drinking and Driving Component, one of five elements of the Community Trials
      Project, involved the implementation of a special drink driving countermeasure in
      the three experimental communities, one in Northern California, one in Southern
      California and another in South Carolina. This intensified enforcement of driving
      under the influence (DUI) was designed to deter potential drinking drivers by
      increasing their perception of the risk of being arrested leading to a reduction
      in the consumption of alcohol before driving. See component detailed description
      in Voas (1997, this issue). The evaluation found that media advocacy training and
      technical assistance resulted in increased DUI news coverage and that additional
      police officer hours for DUI enforcement, greater use of breathalyzer equipment,
      increased officer training and more checkpoints produced increased DUI
      enforcement. The combined effects of increased DUI news coverage and DUI
      enforcement yielded increased public perceived risk of arrest and subsequently
      less drinking and driving. Overall the evaluation found that alcohol-involved
      traffic crashes were reduced as a result of this component in the experimental
      communities as contrasted with the matched comparison communities.

PMID- 9231447
TI  - A community-wide Responsible Beverage Service program in three communities: early
      findings.
AB  - Evidence accumulating over the past 10 years or so suggests that commercial
      servers of alcoholic beverages will intervene to reduce levels of impairment
      among their patrons and will refuse service to intoxicated customers. While some
      Responsible Beverage Service (RBS) programs have had significant effects on
      server and patron behavior, others have not. This leads us to consider issues of
      implementation and program effectiveness. In the current paper, a community-wide
      RBS program is described in some detail. The program was comprised by a larger
      comprehensive community intervention project in three sites across California and
      South Carolina. Process evaluation data, to track program implementation and
      proximal effects, provide early findings. Expressed support for RBS principles
      was high for both the public and the hospitality industry in all sites. A
      telephone survey of managers also suggests that prevention policies at bars and
      restaurants are beginning to show up, but a direct measure of server intervention
      with heavy drinkers does not yet demonstrate a program effect.

PMID- 9231448
TI  - Preventing sales of alcohol to minors: results from a community trial.
AB  - This paper reports an evaluation of a community-based approach to prevent
      underage sales of alcohol. The interventions focused on (a) enforcement of
      underage sales laws, (b) responsible beverage service (RBS) training and (c)
      media advocacy. The interventions were implemented in three experimental
      communities located in California and South Carolina. Purchase survey data were
      obtained before and after the interventions in each experimental community and in
      three matched comparison communities. Logistic regression analyses of the
      purchase survey data for the individual community pairs and for the combined
      communities showed that sales to apparent minors were significantly reduced in
      the experimental sites. The findings indicate that these environmental
      interventions are promising prevention tools for communities that seek to reduce
      underage drinking.

PMID- 9231450
TI  - Use of spatial models for community program evaluation of changes in alcohol
      outlet distribution.
AB  - Alcohol outlets have geographic and spatial characteristics which are important
      for researchers to consider when planning and evaluating community prevention
      programs. Community-level data used in monitoring alcohol problems across
      community areas and over time exhibit spatial dependencies. Statistical
      procedures which depend on assumptions of independence may fail to give proper
      results in such a situation. Specific statistical techniques have been developed
      which adjust for the effects of spatial dependencies in measures across
      geography. This paper provides an example of the creation and use of computer
      Geographic Information Systems to display community alcohol outlets and alcohol
      involved problems and the use of statistical analysis techniques which account
      for such spatial dependencies over time. This paper introduces the concepts,
      terminology, and justification for considering spatial analysis in community
      prevention planning, research and evaluation. The selection of a geographical
      unit of analysis will be discussed. Finally, as a demonstration, a variety of
      spatial statistics are applied to community spatial data for evaluation.

PMID- 9231449
TI  - Community prevention and alcohol retail access.
AB  - This paper describes the design, rationale and implementation of the Alcohol
      Access Component within the Community Trials Project of the Prevention Research
      Center. The Alcohol Access Component was to reduce the concentration or density
      of alcohol outlets in each experimental community by a combination of local
      zoning and land-use planning approaches which was an effect to occur over several
      years. During the time of this trial, local regulations of alcohol outlets and
      public sites for drinking were changed in all three experimental communities. The
      amount of such alcohol policy change exceeded the goals for this component.

PMID- 9231451
TI  - Application of local policy to prevent alcohol problems: experiences from a
      community trial.
AB  - Alcohol policy conventionally has been established at the national or regional,
      state and provincial levels. Alcohol policy at any level is not actually limited
      to the regulation and control of alcohol production, wholesale distribution, and
      retail sales. There are a number of alternatives for setting alcohol policies
      within a local community. Building upon existing national and state/provincial
      laws, policy makers at the community level can set priorities for allocating
      resources and enforcing laws related to drinking and driving, underage alcohol
      sales, alcohol serving practices of bars and restaurants and geographical density
      of alcohol outlets in the community. This paper concludes from the Community
      Trials Project that policies established at the local level can reduce alcohol
      problems.

PMID- 9231452
TI  - Summing up: lessons from a comprehensive community prevention trial.
AB  - This paper presents the findings and lessons from a community prevention trial
      involving three experimental communities in the United States to reduce alcohol
      involved trauma. The paper provides recommendations for other community
      prevention efforts. Effectiveness was demonstrated by: (a) 78 fewer alcohol
      involved traffic crashes as a result of the Drinking and Driving Component alone
      (approximately a 10% reduction); (b) a significant reduction in underage sales of
      alcohol, i.e. off-premise outlets sold to minors about one-half as often as in
      comparison communities; (c) increased implementation of responsible beverage
      service policies by bars and restaurants; and (d) increased adoption of local
      ordinances and regulations to reduce concentrations of alcohol outlets.

PMID- 9231453
TI  - Screening for osteoporosis.

PMID- 9231454
TI  - Cytokines in human breast milk.
AB  - In early life humans derive all their nutrients from milk. Human milk provides
      the neonate with not only a food source but also a source of biologically active
      molecules such as hormones, growth factors and cytokines. Cytokines are
      multifunctional glycoproteins involved in cell communication and immune system
      activation. Two of these cytokines, granulocyte-colony stimulating factor (G-CSF)
      and interleukin-6 (IL-6), are present in variable concentrations in human milk.
      We measured G-CSF and IL-6 concentrations in healthy nursing mothers. The 30 milk
      samples assayed contained G-CSF levels from 14 pg/mL to > 2500 pg/mL. Of the 28
      milk samples assayed for IL-6, 24 contained levels from 0.81 pg/mL to 306 pg/ mL.
      The remainder had levels below the detection limit of the assay. These
      biologically active molecules may play a role in neonatal growth and development,
      and may also protect the infant against infection.

PMID- 9231455
TI  - Sectioning fresh human bone: the reduction of aerosol and physical hazards.
AB  - Musculoskeletal research demands an accurate model on which to work, and fresh
      frozen human bone is an ideal material. However, there is increasing concern over
      the biohazard that this represents. A method is reported that reduces the
      biohazard, and two research situations are described. Both use
      polymethylmethacrylate (PMMA) bone cement as an interface between the human
      tissue and the cutting device, which allows solid and suitable geometry for vice
      fixation. A method of bone cutting that enables remote operation is described;
      this method may reduce the risk of disease transmission by aerosol, and prove
      useful to all in this field of research.

PMID- 9231456
TI  - Activities of potential tumour marker enzymes during induced differentiation in
      HL-60 and U-937 cells.
AB  - HL-60 and U-937 cells were used as models to assess the involvement of the
      enzymes of thymidine metabolism in differentiation. Both cell types showed
      decreased thymidine kinase and thymidylate synthase but increased thymidine
      phosphorylase activities in response to the induction of differentiation by
      dimethylsulfoxide and 12-O-tetradecanoylphorbol 13-acetate. This was accompanied
      by a greater than three-fold increase in the stimulation of superoxide production
      in both cell lines. Thymidylate synthase and thymidine kinase activities were
      noted as potential markers of leukaemic cell proliferation while thymidine
      phosphorylase and superoxide production correlated well with differentiated
      phenotypes. Prolonged treatment of U-937 by 12-O-tetradecanoylphorbol 13-acetate
      resulted in a marked de-differentiation, indicating overstimulation of one or
      more of the isoforms of protein kinase C.

PMID- 9231457
TI  - Serum sialic acid and its relationship to various haematological parameters,
      including erythrocyte sedimentation rate.
AB  - Serum total sialic acid (TSA) has been reported to be a marker or risk factor for
      cardiovascular disease. The reason for this is not clear, although it has been
      suggested that serum TSA is a marker of the acute phase response. We measured
      serum TSA and various haematological parameters in 40 subjects. Significant
      correlations of serum TSA with erythrocyte sedimentation rate (ESR) (r = 0.65, P
      < 0.0001), platelet count (r = 0.65, P < 0.0001) and neutrophil count (r = 0.33,
      P < 0.05) were found. There was an inverse correlation with haemoglobin
      concentration (r = -0.62, P < 0.0001) and erythrocyte count (r = -0.42, P <
      0.01).

PMID- 9231458
TI  - Immunoglobulin G sub-class concentrations in South African adults: ethnic
      differences and reference ranges.
AB  - Serum samples from healthy adult volunteers (n = 149) were selected at random
      from disputed paternity cases, laboratory staff and volunteers attending clinical
      trials. Total immunoglobulin G (IgG) and IgG sub-class (IgGSc) concentrations
      were determined by a radial immunodiffusion technique (RID). Standard statistical
      analyses were used to determine differences between groups. Reference ranges of
      IgGSc concentrations were calculated on the resultant groups of data. Total IgG
      and IgGSc concentrations in men and women of the same racial group were similar,
      except for IgG4 which was slightly higher in white males than in white females
      (median: 0.36 g/L vs 0.20 g/L respectively). IgGSc concentrations were higher in
      blacks than in whites (median values: IgG: 17.1 vs 12.1 g/L; IgG1: 11.1 vs 7.6
      g/L; IgG2: 4.3 vs 3.2 g/L; IgG3: 1.2 vs 0.90 g/L respectively) with the exception
      of IgG4 which was similar in both groups (median: 0.29 g/L). It would appear that
      IgGSc values differ among the ethnic groups. Ethnicity must therefore be
      considered when calculating reference ranges. The reference ranges for the IgG
      sub-classes in the two ethnic groups are intended for use in our laboratory and
      in others in South Africa that use the RID technique.

PMID- 9231459
TI  - Toxic shock syndrome in the burned patient.
AB  - Toxic shock syndrome (TSS) has gained notoriety because of its association with
      tampon use. However, there is an increasing awareness of the syndrome on many of
      the specialised burn units in hospitals through the United Kingdom. TSS primarily
      affects children with small-percentage burns, and it is this group of patients
      that normally would be expected to make an uneventful recovery. One unit, where
      100-150 children are admitted per year, has seen four cases of confirmed TSS over
      a two-year period. There does not appear to be the same risk of TSS in adult
      burned patients, and this lower incidence may be the result of an increase in the
      production of antibodies to toxic shock toxins with increase in age.

PMID- 9231460
TI  - Biochemical assay of serum bile acids: methods and applications.
AB  - Immunoassays and bioluminescence assays of bile acids in serum have provided
      relatively simple and sensitive methods for assessing the concentration of
      selected sub-groups of bile acids. However, these assays do not provide full data
      for each of the individual bile acids. The recent development of sensitive
      techniques such as high-performance liquid chromatography (HPLC) and gas-liquid
      chromatography-mass spectrometry (GLC-MS) have made possible the separation and
      quantification of free and conjugated bile acids in biological samples. Several
      studies have demonstrated the value of individual serum bile acid levels and bile
      acid ratios when assessing the hepatic function of experimental animals treated
      with various hepatoxic agents, and in humans with various hepatic disorders.
      Current data show that individual serum bile acids are more sensitive and
      specific as early predictors of hepatic injury, and are an accurate independent
      prognostic indicator. These studies have provided further insight into the
      various determinants of serum bile acid levels in physiological and pathological
      conditions affecting the liver. Future studies using these techniques and perhaps
      monoclonal antibodies, fast atom bombardment-mass spectrometry (FAB-MS) and
      nuclear magnetic resonance (NMR) for bile acid assays may provide both researcher
      and clinician with a reliable, sensitive and specific indicator of hepatic
      injury.

PMID- 9231461
TI  - Nuclear DNA in histological and cytological specimens: measurement and prognostic
      significance.
AB  - In recent years molecular biology techniques have provided new insights into the
      nuclear mechanisms associated with carcinogenesis. These have led to renewed
      interest in the measurement of nuclear DNA for diagnosis, prediction of
      prognosis, and assessing tumour response to therapy. Cytogenetics has been used
      successfully for this purpose for several decades, but technical problems have
      largely restricted this to haematological malignancies. However, technological
      improvements in flow cytometry and image analysis, together with new molecular
      biology techniques for measuring nuclear DNA, are providing useful information on
      nuclear ploidy and proliferative activity in solid tumours. Although many
      problems remain in this field, these new and improved techniques for measuring
      nuclear DNA are beginning to find a role in diagnostic pathology.

PMID- 9231463
TI  - Column agglutination technologies.

PMID- 9231462
TI  - Protamine sulphate used in combination with thrombin to remove fibrinogen prior
      to electrophoresis of heparinised plasma.

PMID- 9231464
TI  - Interference by mannitol in total protein estimation.

PMID- 9231465
TI  - Mental health care in the community: what should be on the agenda?

PMID- 9231466
TI  - Quality improvement in general practice.

PMID- 9231467
TI  - Poles apart? The views of general practitioners and family health services
      authority advisers on prescribing cost issues.
AB  - BACKGROUND: In 1994, an Audit Commission report estimated that Pounds 425 million
      could be saved from the national drug budget if general practitioners (GPs)
      altered their prescribing in various ways. AIM: To assess the views of GPs and
      family health services authority (FHSA) advisers on issues similar to those
      raised in the Audit Commission report. METHOD: A questionnaire was sent to a 1 in
      20 sample of GPs from 33 randomly selected FHSA areas (n = 576) and all FHSA
      advisers (n = 285). RESULTS: A total of 419 (72.7%) GPs and 234 (82.1%) advisers
      replied. There were statistically significant differences (P < 0.01) between GPs
      and advisers on all but one of the statements. In particular, there were marked
      differences on some of the statements relating to substitution with cheaper
      similar drugs. Differences were smaller for statements on the use of drugs of
      limited therapeutic value, the range of drugs prescribed, and practice
      prescribing policies. Differences were noted between subgroups of GPs in response
      to some of the statements. CONCLUSION: The majority of GPs in this survey gave
      responses that were supportive of many of the types of suggestion made by the
      Audit Commission. However, it is suggested that differences of opinion between
      GPs and FHSA advisers may have implications for the development of strategies to
      control prescribing costs.

PMID- 9231468
TI  - Determining priorities for change in primary care: the value of practice-based
      needs assessment.
AB  - BACKGROUND: Primary care is being expected to expand the range of services it
      provides, and to take on many of the tasks traditionally provided in secondary
      care. At the same time, general practitioners (GPs) will become increasingly
      responsible for assessing their patients' health care needs and commissioning
      care from other providers. This article describes an approach taken in one
      general practice to meet these difficult challenges. AIM: To examine whether
      information on health and health care needs, when used as the basis for a
      priority setting exercise, can provide a useful first step in planning primary
      care provision within a practice. METHOD: A three-stage process of information
      gathering from a number of sources, including continuous data recording of
      patient contacts and a postal survey of all adults registered with the practice,
      identification of key findings and discussion of associated issues, and priority
      setting of proposals for practice development using the nominal group technique.
      RESULTS: Continuous data recording of patient contacts with GPs and the practice
      nurse provided data on 4489 GP contacts with 2027 patients, 1000 district nurse
      contacts with 101 patients, and 361 health visitor contacts with 172 clients.
      More than 70% of patient records had been computerized, with 600 diagnostic READ
      codes identified and 11,500 separate entries made. The socioeconomic and health
      survey questionnaire achieved an 84% response rate. Following the priority
      setting exercise, 28 proposed practice developments were identified. These were
      reduced to a final list of eight. CONCLUSION: A comprehensive method of practice
      based needs assessment, when used as the basis for some form of priority setting,
      has great potential in helping to plan primary care services within a practice.
      The success of such initiatives will require a substantial investment of
      resources in primary care and fundamental changes to the way in which primary
      care is funded.

PMID- 9231469
TI  - Selection for postgraduate training for general practice: the role of knowledge
      tests.
AB  - BACKGROUND: Postgraduate training for general practice is a legal requirement in
      most countries of the European Community, and includes posts in general practice
      as well as in hospitals. The effectiveness of the training has not been fully
      evaluated, and it is largely unknown whether the results are satisfactory or what
      the impact of the separate training components is--nor is it known which
      characteristics or prior achievements of the trainee influence the end-of
      training performance. AIM: To determine the value of knowledge tests in the
      context of entry selection for postgraduate training in general practice.
      METHODS: Three (equated) knowledge tests were administered during the two years'
      postgraduate training of 85 Dutch trainees. The first test was taken at entrance,
      the second eight months later, and the third shortly before the end of the entire
      training period. Complete data for 57 trainees were available for analysis. A
      multiple regression analysis was performed to estimate the predictive values of
      test 1 and test 2 scores, separately and in combination, for test 3 scores. Since
      the knowledge test may be used for selection purposes, the analysis was repeated
      using logistic regression with two pass/fail criteria: a 'minimum criterion' and
      an 'excellence criterion'. RESULTS: Neither of the two analyses yielded a
      predictive value of test 1 that was high enough to warrant the use of knowledge
      tests in the context of entry selection. A 'below minimum' score on test 2
      correlated 100% with a 'below minimum' score on test 3. However, the positive
      predictive value of an above minimum score on test 2 was only 86%. CONCLUSIONS:
      The knowledge tests used in this study are not suitable in the context of entry
      selection. However, trainees that score 'below minimum' after eight months of
      training may be regarded as 'at risk' in that they will probably score 'below
      minimum' at the end of training.

PMID- 9231471
TI  - Physical activity promotion through primary health care in England.
AB  - BACKGROUND: There is increasing research supporting the argument for a beneficial
      link between physical activity and health maintenance and, in the past five
      years, this has led to a growth in physical activity promotion schemes involving
      primary health care. AIM: To document and critically examine the extent and
      nature of physical activity promotion in general practice in England. METHOD: A
      postal survey to all family health services authorities and primary care
      facilitators was conducted to identify existing and planned activity promotion
      schemes involving primary health care. Telephone interviews with leaders from 50
      selected schemes and further detailed case studies of 11 schemes provided
      descriptive information of the nature of physical activity promotion. RESULTS:
      The initial phase revealed 157 existing schemes and a further 35 planned schemes.
      Two basic models of physical activity promotion were identified that were
      distinguishable by the primary location of the management of the patient.
      Practice-managed interventions (32%) involve on-site counselling to change the
      behaviour of patients. Leisure centre-managed projects (68%), sometimes termed
      'exercise by prescription' or 'general practitioner referral for exercise'
      schemes, involve the identification of suitable patients and their referral to 10
      to 12-week-long leisure centre based exercise induction courses. The projects in
      the planning stage were all of the latter type, indicating this as the favoured
      model. Although such schemes were generally successful in attracting patients, in
      all cases they involved less than 1% of the patient base from which they were
      drawn. CONCLUSION: There is evidence of successful recruitment, increased short
      term physical activity and fitness, and improvements in the well-being of
      patients. However, schemes are inadequately resourced for rigorous long-term
      evaluation; therefore, conclusions regarding the cost-effectiveness of the two
      models are not possible.

PMID- 9231470
TI  - Population-based prevention of influenza in Dutch general practice.
AB  - BACKGROUND: Although the effectiveness of influenza vaccination in high-risk
      groups has been proven, vaccine coverage continues to be less than 50% in The
      Netherlands. To improve vaccination rates, data on the organizational factors,
      which should be targeted in population-based prevention of influenza, is
      essential. AIM: To assess the organizational factors in Dutch general practice,
      which were associated with the influenza vaccination rate in 1994. METHOD: A
      retrospective questionnaire study was undertaken in 1586 of the 4758 Dutch
      general practices, which were randomly selected. A total of 1251 (79%) practices
      returned a questionnaire. The items verified were practice profile, urbanization,
      delegation index, use of computer-based patient records, influenza vaccination
      characteristics and influenza vaccination rate. RESULTS: No differences were
      found with regard to the percentage of single-handed practices (65%), practices
      situated in urban area (38%), practices with a pharmacy (12%), patients insured
      by the National Health Service (59%) and use of computer-based patient records
      (57%) when compared with national statistics. The mean overall influenza
      vaccination rate was 9.0% (SD 4.0%). Using a logistic regression analysis, a high
      vaccination rate (> or = 9%) was associated with the use of personal reminders
      (odds ratio (OR) 1.7, 1.3-2.2), monitoring patient compliance (OR 1.8, 1.3-2.4),
      marking risk patients in computer-based patient records (OR 1.3, 1.0-1.6), a
      small number of patients per full-time practice assistant (OR 1.5, 1.1-1.9),
      urban areas (OR 1.6, 1.3-2.1) and single-handed practices (OR 1.5, 1.1-1.9).
      CONCLUSION: Improvement of vaccination rates in high-risk patients may be
      achievable by promoting the use of personal reminders and computer-based patient
      records, as well as monitoring patient compliance. In addition, the role of
      practice assistants with regard to preventive activities should be developed
      further. Practices situated in rural areas and group practices may need more
      support with a population-based approach for the prevention of influenza.

PMID- 9231472
TI  - Finding diabetics--a method of screening in general practice.
AB  - BACKGROUND: It is well known that many diabetic patients go undiagnosed until
      complications have started to develop. Screening can be expensive in time and
      money, and ineffective, and is therefore unpopular with general practitioners
      (GPs). AIM: This study aimed to develop a screening method that was cost
      effective and practical within the setting of an ordinary general practice.
      METHOD: Urine-testing sticks for glucose were sent with an explanatory letter to
      all (1736) non-diabetic subjects over 50 years old in a general practice. At the
      same time, diabetic recall and care were audited and improved in the practice.
      RESULTS: Reply slips were received from 1204 patients (69.4%). Of these, 2.6%
      were positive and 97.4% were negative. Eight new diabetic patients were therefore
      found at a cost of 78.25 pounds each. CONCLUSION: This method of screening a
      selected part of a general practice population is practical and effective. Apart
      from the human cost, the financial cost of finding a new diabetic patient is
      small compared with that of caring for a diabetic patient who is blind or an
      amputee.

PMID- 9231473
TI  - A pilot study of a randomized controlled trial of pragmatic eradication of
      Helicobactor pylori in primary care.
AB  - We report on a pilot study for a randomized control trial of pragmatic
      eradication of Helicobacter Pylori in primary care. Although the sample size is
      small, pragmatic eradication is likely to be cost-effective for patients with
      documented or suspected peptic ulcer disease on maintenance acid suppression
      therapy in primary care.

PMID- 9231474
TI  - Analgesics: a comparison of therapeutic knowledge and inter-professional liaison
      between general practitioners and community pharmacists.
AB  - The aim of this study was to ascertain general practitioners' (GPs') and
      pharmacists' knowledge of analgesics, to establish professional opinion on their
      use, and to assess the extent of pharmacist input into the prescribing of
      analgesics. Pharmacists displayed a better knowledge of analgesics than their
      colleagues in general practice, but had little input into the prescribing
      decisions made by GPs. Pharmacists' knowledge is not being put to best use in
      contributing to the preparation of practice formularies, and links between these
      two health professional groups need to be developed further.

PMID- 9231475
TI  - Practice charters: a survey in south and west Devon.
AB  - A postal survey was conducted in 1995 in South and West Devon to explore the
      perceived value of practice charters; 79 (77%) of the practices surveyed had a
      charter and 24 (23%) did not. Three-quarters of responding practices with a
      charter felt that its effects were neither positive nor negative. Fears about
      charters raising patients' expectations and increasing the number of complaints
      appear to have been unfounded, but at least 14 of the practices were still not
      intending to produce their own charter.

PMID- 9231478
TI  - Quality-of-life measures in asthma--do they matter to the GP?
AB  - Asthma is a condition which incurs a great cost to the National Health Service,
      to the economy and above all to the patient in terms of loss of quality of life.
      Treatments for asthma need to be evaluated for their cost-effectiveness.
      Traditional outcome measures, such as airflow measurements have their
      limitations, especially in mild to moderate asthma. Quality-of-life measurements
      represent the impact of asthma on the everyday lives of asthmatics across the
      whole disease spectrum. Disease specific quality-of-life questionnaires, such as
      the Asthma Quality-of-Life Questionnaire (AQLQ), provide reliable instruments in
      reflecting disease severity, but also in detecting changes in quality of life
      produced by different asthma treatments. Quality-of-life measures are becoming
      increasingly important and are end-points of therapeutic asthma trials in primary
      care, but should be used in conjunction with more surrogate markers of asthma
      severity such as peak flow.

PMID- 9231476
TI  - Is vasectomy harmful to health?
AB  - Since the late 1960s, vasectomy has been a popular and widely used form of
      contraceptive in Britain for couples who do not want to have any more children.
      However, throughout the past decade there has been considerable concern about the
      safety of this procedure. This paper reviews the current opinion on the possible
      health considerations associated with this operation and shows that the latest
      news is mostly reassuring.

PMID- 9231479
TI  - William Pickles Lecture 1997. A liberal education: teaching, learning and
      research in general practice.

PMID- 9231477
TI  - Endometrial sampling and general practice.
AB  - Endometrial sampling is an 'office' technique that has gained widespread
      acceptance in the United States (US). It is as accurate as dilatation and
      curettage (D&C) in the diagnosis of endometrial atypia and carcinoma. It appears
      to be the most suitable method of endometrial assessment for general practice. It
      has the potential for the earlier detection of endometrial abnormality and for
      increasing the number of women with abnormal vaginal bleeding who can be wholly
      managed within primary care. However, research is lacking on the effect of the
      widespread introduction of the technique into general practice. This paper puts
      forward recommendations for the use of endometrial sampling by general
      practitioners (GPs) based on current evidence.

PMID- 9231480
TI  - Breastfeeding problems.

PMID- 9231481
TI  - Benign prostatic hyperplasia.

PMID- 9231482
TI  - Randomized controlled trials.

PMID- 9231483
TI  - General practice--a postmodern specialty?

PMID- 9231484
TI  - General practice--a postmodern specialty?

PMID- 9231485
TI  - General practice--a postmodern specialty?

PMID- 9231486
TI  - Resuscitation equipment and general practitioners.

PMID- 9231487
TI  - Management of involuntary childlessness.

PMID- 9231488
TI  - Practice nurse intervention.

PMID- 9231489
TI  - The risk of cardiovascular disease in hypertensive patients.

PMID- 9231490
TI  - Non-compliance to long-term asthma treatment--our greatest challenge [corrected].

PMID- 9231491
TI  - Six characters in search of an author.

PMID- 9231492
TI  - Cutaneous infection in meatworkers.
AB  - Cutaneous infections occurring in abattoir workers are an under-recognized cause
      of occupational morbidity. This study examined the incident rates of cutaneous
      infection in a medium sized metropolitan abattoir in Adelaide, South Australia.
      The results show that cutaneous infections are common (0.65 per 1,000 working
      days) and that there exists an association between the nature of the work task
      within the abattoir and infection rates. Specifically, those individuals handling
      animal hides have higher rates of infection compared to other workers. The
      implications of these findings are discussed with particular emphasis on the
      prevention of these infections.

PMID- 9231493
TI  - Status and development of critical incident stress management services in the
      United Kingdom National Health Service and other emergency services combined:
      1993-1996.
AB  - Surveys conducted amongst members of the Association of NHS Occupational
      Physicians indicate few changes in the status and development of Critical
      Incident Stress Management Services (CISMS) in the United Kingdom National Health
      Service between 1993 and 1996. Limited CISMS are confirmed by the majority of
      respondents in the two surveys with developments having typically occurred within
      long-established staff care services such as counselling. In 1996 NHS provision
      is typically based on the independent use of own resources. A 1996 comparison of
      NHS with pooled returns from Ambulance Services, Fire Brigades and Social
      Services Departments indicates few variations in status, provision and levels of
      expertise in the delivery of CISMS. Other emergency services co-operate to a
      greater extent with each other than does the health care sector. Occupational
      Health Department responders confirm availability of expertise resources to
      provide CISMS, but low priority status frustrates delivery of CISMS. Survey
      results indicate the NHS is at risk of not fulfilling its duty to care for staff
      after major incidents. The establishment of regional centres of CISMS excellence
      with local and national responsibilities is advocated.

PMID- 9231494
TI  - Methods to persuade higher management to invest in health promotion programmes in
      the workplace.
AB  - This study was conducted to find effective methods to persuade higher management
      to invest in workplace health promotion (WHP) programmes. The study included 639
      occupational health professionals selected from the directory of the Japan
      Society for Occupational Health. A questionnaire survey was mailed to health
      professionals throughout Japan in 1992, and all respondents were asked to
      identify themselves. We received 242 replies, which constituted a response rate
      of 38%. Eighty-one per cent of the respondents had attempted to persuade higher
      management to implement a WHP programme. Health professionals frequently
      presented their case to higher management through a safety and health committee
      (SHC), and advice provided at the SHC was perceived to be the most effective
      method by occupational nurses (ONs) and safety and health supervisors (SHSs).
      This method was rated second by occupational physicians (OPs), who thought
      recommendations from OPs stipulated by the Industrial Safety and Health Law to be
      most effective. Statistics on medical examinations constituted the data most
      frequently used to persuade higher management, followed by reports on worksite
      inspections and health care plans. Nearly 90% of OPs and 80% of ONs and SHSs felt
      that the above methods were fairly successful.

PMID- 9231495
TI  - Chronic fatigue syndrome and occupational health.
AB  - Chronic fatigue syndrome (CFS) is a controversial condition that many
      occupational physicians find difficult to advise on. In this article we review
      the nature and definition of CFS, the principal aetiologic hypotheses and the
      evidence concerning prognosis. We also outline a practical approach to patient
      assessment, diagnosis and management. The conclusions of this review are then
      applied to the disability discrimination field. The implications of the new UK
      occupational health legislation are also examined. Despite continuing controversy
      about the status, aetiology and optimum management of CFS, we argue that much can
      be done to improve the outcome for patients with this condition. The most urgent
      needs are for improved education and rehabilitation, especially in regard to
      employment. Occupational physicians are well placed to play an important and
      unique role in meeting these needs.

PMID- 9231496
TI  - The performance of the ICEROSS prostheses amongst transtibial amputees with a
      special reference to the workplace--a preliminary study. Icelandic Roll on
      Silicone Socket.
AB  - A clinical trial was conducted to evaluate the efficiency of ICEROSS on randomly
      selected 46 male transtibial amputees. After rejection, only 27 (58.69%) amputees
      volunteered for various stages of the ICEROSS trial. All 27 were categorized into
      Group A-persons in employment (n = 16) and Group B-persons out of employment or
      economically inactive (n = 11). The study was conducted on the basis of
      questionnaire information, clinical examination and objective tests. The pre- and
      post-ICEROSS status were compared between the groups. Group A was younger and did
      better. Trauma was the main cause of amputation. There were certain changes of
      the stump before and after ICEROSS. The amputees with ICEROSS suspension
      performed better and had improved mobility in Group A. At the workplace, dynamic
      activities were less than the static activities (p < 0.001) and there were
      overall improvements in comfort and performance of amputees with ICEROSS.

PMID- 9231497
TI  - Health and safety behaviour and compliance in electroplating workshops.
AB  - Skin problems are reputedly common in electroplaters. To examine the steps taken
      by employers and employees to prevent or control skin problems, we visited six
      randomly selected electroplating establishments in Dorset and interviewed the
      employers and 50 of the employees using structured questionnaires. Several of the
      companies had not complied with the statutory requirements of the Control of
      Substances Hazardous to Health (COSHH) Regulations 1988, and deficiencies were
      evident in assessment, control and health surveillance. A third of the employees
      had current or recent work-related skin problems, typically dermatitis. Workers
      were generally ignorant about the hazards of materials handled. They knew about
      personal protective equipment, but did not always use it, or used gloveware that
      was deficient or contaminated. Only one in five employees adopted a rudimentary
      skin care programme; many were unaware of the provision for skin care. There is
      an urgent need for better training and more attention to skin care in
      electroplating workshops.

PMID- 9231498
TI  - Ethical and metaethical criteria for an emerging technology: risk assessment.
AB  - This paper examines ethical criteria for the shaping of an emerging technology
      applied internationally in environmental regulation: quantitative risk assessment
      risk management. The role of the physician in its application, especially in the
      genetic testing that will be employed, underlines the importance of understanding
      the nature and prospects for reshaping of this technology to enable ethical
      practice. The Cartesian or mechanistic model (which currently dominates the
      technology) excludes factors of emotion, making the connection between assessment
      and management unfruitful functionally and ethically, and makes the model
      unresponsive to human needs. The emotional factors, nested and mediated in the
      organic hierarchy of the ecologically-defined community, constitute key
      psychological, social, cultural and political elements of the total burden of
      risk. Ethical criteria consistent with an open society are suggested for
      reshaping the model to enable effective management.

PMID- 9231499
TI  - Planning research.
AB  - The starting point for any research project should be a question. Once this has
      been defined and the relevant scientific literature reviewed, a protocol should
      be drawn up. This will be used not only as a guide to the conduct of the study
      and in the preparation of the final report, but also in seeking any financial
      support and approvals that are required for the investigation. A protocol is
      normally arranged in sections covering the background to the study, the
      question(s) that it will address, the methods that will be used for the
      collection and analysis of data, the statistical power of the investigation
      (where relevant), any ethical considerations, and the financial input that will
      be needed. A pilot study is often helpful where aspects of the study method are
      untried or of uncertain validity.

PMID- 9231502
TI  - [Pharmacovigilance off the beaten track: herbal surveillance or pharmacovigilance
      of medicinal plants].
AB  - For several years, herbal medicines have been increasingly consumed by patients
      without prescription. They are traditionally innocuous but as medicinal products
      they require drug surveillance in order to identify their risks. However, the
      first concern is to give them a legal status, to evaluate their efficacy and to
      control their safety. Published data show that the risk is due either to a
      contaminant or to an added drug or falsification. Since 1985, the Regional
      Pharmacovigilance Centres have received about 341 reports of undesirable effects
      due to herbal medicines: among them 30 cases of hepatitis were reported
      associated with germander which has been now withdrawn from the French market.
      This example well illustrates the role of the national system and its
      responsibility for collecting and evaluating ADRs due to herbal medicines.

PMID- 9231501
TI  - [Side effects of mesotherapy].

PMID- 9231500
TI  - Occupational asthma and rhinitis caused by 1,2-benzisothiazolin-3-one in a
      chemical worker.
AB  - We report a case of occupational asthma and rhinitis caused by inhalation of 1,2
      benzisothiazolin-3-one, an additive used as a microbicidal in detergent
      production, in a 26-year-old man employed in a chemical factory producing
      detergents. The subject's task consisted of pouring raw materials into the
      recipient of a machine which mixed the substances. Two months after the beginning
      of this job the patient complained of rhinitis and asthma at the workplace. The
      specific challenge test with 1,2-benzisothiazolin-3-one, one of the raw materials
      to which the subject was exposed, provoked an immediate prolonged asthmatic
      response and nasal symptoms, whereas exposure to other agents (e.g., alpha
      amylase, alcalase or bezalkonium chloride) to which the patient was also exposed
      at work did not. To our knowledge this is the first case of occupational asthma
      and rhinitis caused by this compound.

PMID- 9231503
TI  - [Pharmacovigilance of self-medication].
AB  - Self-medication can be defined as obtaining and consuming one (or more) drug (s)
      without the advice of a physician either for diagnosis, prescription or
      surveillance of the treatment. Self-medication accounts for around 5 to 10 per
      cent of drug sales in France. There are few data on side effects of self
      medication in France. The side effects of drugs taken by self-medication and
      reported to the Midi-Pyrenees drugs surveillance centre between January 1993 and
      June 1996 were investigated in the present study. There were 65 reports, mainly
      in women (58 per cent), i.e. around 2 per cent of the reports to the regional
      drugs surveillance centre. The most frequent side effects are neurological (32
      per cent: mainly headache, vertigo, agitation, etc.), dermatological (18 per
      cent, mainly allergy), hepatic (10 per cent), digestive (7 per cent, mainly
      diarrhoea). There were 10 cases of anaphylactic shock and/or Quincke oedema. The
      drugs most frequently involved were analgesics and non-steroidal anti
      inflammatory drugs (47 cases), neuropsychotropic drugs (7 cases), dermatological
      drugs (6 cases) or otorhinolaryngological drugs (6 cases).... 'Serious' side
      effects occurred in 40 per cent of the cases including 3 deaths. 'Severe' side
      effects were observed in 77 per cent of the reports. This study shows that the
      side effects of self-medication are relatively frequent and can be serious. They
      occurred more often in women than in men, mainly with analgesic and anti
      inflammatory drugs. These data permit a better analysis of the risk/benefit ratio
      of self-medication. Drug surveillance studies of self-medication must be
      developed.

PMID- 9231504
TI  - [Treatment with low dose methotrexate in rheumatoid arthritis: risk factors for
      severe complications].
AB  - Treatment with low dose methotrexate in rheumatoid arthritis is associated with
      serious side effects in about 5 per cent of cases (respiratory, haematological or
      infectious). The goal of a null risk seems unrealistic because of the
      idiosyncrasy of some of the risks and our poor understanding of others (enzymatic
      polymorphisms might be operational, and infectious agents could act as co
      factors). However, risk can be greatly reduced by a careful selection of
      patients. Some contraindications are strict: poor compliance and the possibility
      of mistake in the timing of the administration; pregnancy or desire for
      pregnancy; treatment with trimetoprim; haemodialysis; renal insufficiency
      (clearance < or = 50 ml/min) (and therefore old age), alcoholism. Others remain
      relative although well established; hypoalbuminaemia, diabetes mellitus, obesity,
      past infection with hepatitis virus. Others are dubious: starvation,
      macrocytosis, surgical stress, NSAIDs. An extensive large study of side effects
      is warranted.

PMID- 9231505
TI  - [Pharmacovigilance of new antidepressants: evaluation of neuro-psychobehavioral
      disorders].
AB  - Drug surveillance data can be obtained from different sources: spontaneous French
      and European reporting, data from WHO, bibliographic analysis. We are more
      interested, in this paper, in the type of data obtained than in the surveillance
      of each antidepressant. Our study is focused on psychiatric and neurobehavioural
      effects of antidepressants. The French drug surveillance database was examined
      for reactions associated with fluoxetine. Psychiatric side effects are not the
      most frequent. The psychiatric safety profiles of the three SSRIs (fluoxetine,
      fluvoxamine and paroxetine) are similar. However withdrawal reactions with
      fluvoxamine and paroxetine occur in a greater proportion of reports (13 and 14
      per cent) than with fluoxetine (1.5 per cent). In contrast, pharmacodependance
      was observed in 79 per cent of reports with amineptine. Tricyclic antidepressants
      do not seem to confer increased risk of teratogenesis. Preliminary data regarding
      risk of prenatal exposure to fluoxetine suggest that its use during pregnancy is
      relatively safe. Data regarding neurobehavioural effects of prenatal exposure are
      lacking for all antidepressants. Cognitive disorders induced by antidepressants
      are complex, due to the involvement of several factors that can intervene in the
      pathogenesis and evaluation of these disorders : most studies evaluate the
      modifications of neurobehavioural effects in healthy subjects, few studies
      concern chronic patients. Proposals are made to improve the evaluation of these
      side effects.

PMID- 9231506
TI  - [Good practices of publication of clinical cases of pharmacovigilance: comments,
      Groupe de Travail sur les Bonnes Pratiques de Publication de Cliniques en
      Pharmacovigilance: commentary].
AB  - This paper introduces some comments on the complete text of Good
      Pharmacovigilance Publishing Practices, which forms appendix number 2 of the Good
      Pharmacovigilance Practices now published by the French Drug Agency, as was Good
      Clinical Practices. Each good practice is printed in italic and presented in a
      frame; the following comments are designed to facilitate its application. The
      technical terms that are used in this text are presented according to the
      glossary in Good Pharmacovigilance Practices.

PMID- 9231507
TI  - [Pharmacokinetics of methotrexate in rheumatoid arthritis: therapeutic
      implications].
AB  - The fraction of oral methotrexate (MTX) absorbed averages 70 per cent at low
      doses (< or = 10 mg/m2), both fasting and after food. The mean binding of MTX to
      serum albumin is 42-57 per cent. Less than 10 per cent of MTX is oxidised to 7-OH
      MTX. Furthermore, MTX is partly converted to polyglutamate derivatives which
      accumulate in some cells resulting in sustained efficacy of the drug in spite of
      its relatively short plasma elimination half-life. MTX is mainly excreted by the
      kidney as intact drug. Accordingly careful monitoring of renal function is
      justified. MTX undergoes bidirectional transport within the renal tubules leading
      to drug interactions. Oral, intramuscular and subcutaneous routes of
      administration were reported to result in comparable bioavailability. There is a
      marked interindividual variability in MTX disposition. Conversely, the
      intraindividual variability is moderate even over a long time period. Finally, no
      clear relationship between pharmacokinetic parameters and clinical response or
      toxicity has been found in patients with rheumatoid arthritis.

PMID- 9231508
TI  - [Methotrexate and non-steroidal anti-inflammatory agent combination in rheumatoid
      arthritis].
AB  - It is well known that methotrexate (MTX), used at high dosage in cancer patients,
      must not be combined with a non-steroidal anti-inflammatory drug (NSAID) because
      of high risk of side effects; prescribed at low dosage (< or = 15 mg per week) in
      rheumatoid arthritis patients, MTX is often combined with an NSAID. Some cases
      reported in the literature underline the potential toxicity of the association of
      low dose MTX with an NSAID, but most of the pharmacological studies do not
      confirm this hypothesis. Except for salicylates, NSAIDs do not affect the
      absorption, distribution, protein binding, area under the curve, half-life, or
      the elimination of MTX. Therefore, if necessary, MTX (< or = 15 mg per week) can
      be combined with an NSAID during the treatment of rheumatoid arthritis.

PMID- 9231509
TI  - [Mycophenolate mofetil, a new immunosuppressive agent. Is pharmacokinetic
      monitoring justified?].
AB  - Mycophenolate mofetil is a new immunosuppressive agent which is indicated in
      combination with cyclosporin A and a corticosteroid for the prophylaxis of acute
      transplant rejection in patients receiving allogenic renal transplants. It is an
      ester prodrug rapidly hydrolysed to mycophenolic acid, an active metabolite. The
      mechanism of action of mycophenolic acid is different from that of other known
      immunosuppressive drugs: it inhibits the activity of inosine monophosphate
      deshydrogenase, an enzyme responsible for the de novo pathway of guanosine
      nucleotide synthesis in B and T lymphocytes and slows down their proliferative
      response. Should mycophenolic acid plasma concentrations be monitored? To date,
      all available data are assessed and more particularly:--the doses of 1 or 1.5 g
      administered twice daily,--a pilot, open-label multicentre study which showed a
      decreased incidence of acute rejection episodes in patients with steady state
      AUC0-12 h plasma levels < 40 micrograms.ml-1.h.--adverse events (mainly
      gastrointestinal, blood and lymphatic disorders) which appear more frequently in
      patients receiving 3 g/day than in patients receiving 2 g/day and which do not
      seem to be correlated with plasma concentrations of mycophenolic acid. The
      examination of these data clearly shows that additional investigations are
      necessary to better clarify the relationship between plasma mycophenolic acid
      concentration and side effects in order to provide a scientific rationale for
      monitoring the plasma concentrations on a regular basis.

PMID- 9231510
TI  - [Apropos of recent antidepressant drugs: some pharmacological comments].
AB  - Since the discovery of imipramine by Kubn in 1958, several hypotheses have been
      developed in order to explain the antidepressant properties of thymoanaleptic
      drugs. These hypotheses have successively used the results of predictive
      psychopharmacology, biological psychiatry and more recently biochemistry of
      depression. These data have led to the discovery of new products with clear
      antidepressant properties but with a stereotyped 'mono' aminergic mechanism of
      action. Among these drugs, the currently most prolific family is the group of
      'selective' serotonin reuptake inhibitors (SSRI). This review discusses the
      mechanism of action of the recently marketed antidepressant drugs, their
      selectivity, drug-induced changes in the synaptic cleft after short and long term
      treatment, the differences in pharmacodynamics, pharmacokinetics,
      pharmacogenetics and drug surveillance between the different agents as well as
      the perspective for the development of new antidepressants.

PMID- 9231511
TI  - [Value of protecting mitochondrial functions during treatment with cyclosporin
      A].
AB  - The use of cyclosporin A is often limited by its nephrotoxicity. This dose
      dependent toxicity can occur in all kinds of transplantation and is reversed with
      drug withdrawal. Cyclosporin A induces a vasoconstriction leading to an increase
      of renal vascular resistance and a reduction of glomerular filtration.
      Histochemical studies show mitochondrial alterations and an excess of cytosolic
      and mitochondrial calcium leading to a decrease of ATP synthesis. Two strategies
      can be evoked for limiting cyclosporin-A-induced nephrotoxicity. First, the use
      of drugs counteracting the vasoconstriction has been proposed. Second, drugs
      acting by restoration of ATP synthesis could also be of interest. For example,
      calcium channel blockers may be used for limiting the Ca2+ fluxes into cells.
      Another way to protect ATP synthesis is to inhibit the cyclosporin-A-induced
      increase of mitochondrial Ca2+ concentrations; Trimetazidine has shown its
      efficiency in vitro for protecting mitochondria against these modifications of
      Ca2+ homeostasis and is under clinical evaluation.

PMID- 9231512
TI  - [Acute poisoning by risperidone and ionic and electrocardiographic changes].

PMID- 9231513
TI  - Expanding the auxiliaries debate.
AB  - The recent debate about the registration of dental auxiliaries and their role in
      the dental team of the future has been a vigorous one, with strongly held
      opinions expressed on all sides. I would like to approach the subject from a
      different perspective by suggesting that the debate so far has been incomplete
      and has omitted the role that other health professionals might play in delivering
      dental care in the community, in particular, the highly qualified community nurse
      or nurse practitioner.

PMID- 9231514
TI  - Evidence-based dentistry--but where is the evidence?

PMID- 9231515
TI  - Treating oral candidiasis: potentially fatal.

PMID- 9231516
TI  - Children's dentistry in the GDS.

PMID- 9231517
TI  - Accidental needle stick injuries.

PMID- 9231518
TI  - The future of dental amalgam: a review of the literature. Part 6: Possible
      harmful effects of mercury from dental amalgam.
AB  - This is the sixth article in a series of seven on the future of dental amalgam.
      It considers the possible toxic and allergic effects which could occur as a
      result of exposure to mercury from dental amalgam. The main toxic effects covered
      are neurotoxicity, kidney dysfunction, reduced immunocompetence, effects on the
      oral and intestinal bacterial flora, fetal and birth effects and effects on
      general health. The relevant studies in all these areas are described and
      extensively discussed. In addition, the possible development of hypersensitivity
      to mercury from amalgam is described and the production of delayed
      hypersensitivity contact reactions on the skin and mucous membrane, including
      lichenoid lesions, are considered.

PMID- 9231519
TI  - An assessment of capitation in the General Dental Service contract 2. Patterns of
      treatment provided to regularly attending patients.
AB  - OBJECTIVE: To compare the patterns of treatment of general dental practitioners
      working under fee-for-service in 1987/88 with those working under capitation in
      1992/93. DESIGN: 73 randomly selected general dental practitioners working under
      capitation in three contrasting areas in England retrospectively recorded the
      treatment provided during 1992/93 to a random selection of their regularly
      attending 6-12- and 14-15-year-old patients. RESULTS: Mean numbers of
      examinations per year reduced in the three areas from 1.7-1.8 in 1987/88 to 1.2
      1.4 in 1992/93. Mean numbers of visits per patient dropped from 2.5-2.9 to 1.8
      2.2. Mean numbers of fillings in permanent teeth reduced from 0.15-1.04 to 0.09
      0.52 and in deciduous teeth from 0.28-0.53 to 0.24-0.31. Mean percentages of
      children per dentist having extractions fell from 9.3-28.1% to 4.7-16.2% while
      the radiographs reduced from 14.0-9.0% to 6.0-10.6%. Mean percentages of children
      per dentist receiving oral hygiene instruction rose from 18-31% in 1987/88 to 26
      33% in 1992/93. Dietary advice increased from 3-18% to 11-20% and fissure
      sealants from 3-6% to 3-12%. CONCLUSIONS: In 1992/93, dentists working under
      capitation were carrying out fewer examinations, fillings and extractions and
      were taking fewer radiographs for their regularly attending child and adolescent
      patients than dentists working under fee-for-service in 1987/88. These patients
      also attended less frequently for treatment but received marginally more
      preventive care and advice.

PMID- 9231521
TI  - A conservative prosthodontic option for the treatment of edentulous patients with
      atrophic (flat) mandibular ridges.
AB  - The purpose of this article is to highlight the clinical problems encountered in
      the treatment of edentulous patients with atrophic (flat) mandibular ridges. With
      provision of complete dentures in general dental practice in mind, an impression
      technique is described and illustrated. The specific objective of the technique
      discussed is that patients, for whom implant treatment is not a realistic'
      option, may have improved denture function of their lower complete dentures.

PMID- 9231522
TI  - Wilfred Fish Lecture. Self regulation--dentists, discipline and defence.

PMID- 9231520
TI  - Infective endocarditis and the dental practitioner: a review of 53 cases
      involving litigation.
AB  - OBJECTIVE: To review episodes of infective endocarditis involving dental
      procedures that have resulted in litigation and to determine if any clinical
      recommendations can be obtained. DESIGN: 13-year retrospective study.
      INTERVENTION: Patient records were analysed to identify the probable cause of
      infective endocarditis. All were judged to be caused by dental manipulations on
      the basis of dental procedure, cardiac pathology, infecting micro-organism and
      time between onset of infection and dental manipulation. MAIN OUTCOME MEASURES:
      Cases were analysed to check if appropriate national guidelines on antibiotic
      prophylaxis were followed. Status of patient dental records was also evaluated.
      RESULTS: Dental procedures implicated in infective endocarditis were exodontia
      (23), scaling (21), root canal therapy with extra-canal instrumentation (7) and
      minor oral surgery (2). No medical history was recorded in 10 patients. In a
      further 31 medical history was inadequate or out of date. Dentists involved with
      these cases failed to give prophylactic antibiotics (48), prescribed incorrect
      antibiotics (2), or gave antibiotics at inappropriate times (2). There was one
      episode of prophylaxis with amoxycillin failing despite it being given correctly.
      CONCLUSIONS: If litigation is to be avoided dental practitioners must keep
      accurate dental records, take an appropriate medical history that is kept up to
      date and adhere to national guidelines on antibiotic prophylaxis.

PMID- 9231523
TI  - Research on mental health services for Hispanics: targets of convergence.
AB  - In reaching to serve the mental health needs of new catchment neighborhoods, the
      1963 federally funded Community Mental Health Center (CMHC) program stimulated
      culturally oriented research on the effectiveness of mental health services for
      Hispanics. The research, at first scattered and diffuse, has converged on a
      number of targets. This article examines four of the targets of research and how
      they can be brought into a unified perspective if they are viewed in temporal
      order as sequenced disadvantages Hispanics confront in using mental health
      services. The targets can be arrayed longitudinally: reasons for Hispanics'
      underutilization of professional mental health services, difficulties in
      retaining Hispanics in such services, errors in evaluating their mental health,
      and the problems of adapting treatment modalities to their needs.

PMID- 9231524
TI  - Developing theory as a personal response to systemic entrapment.
AB  - The author describes her personal experience with professional powerlessness in
      relation to the attempt by an all-White agency to offer services to a diverse
      clientele and to increase diversity in staff. Her efforts to cope with (a) the
      challenge which this endeavor presented to current knowledge and practice, and
      (b) the ensuring conflict, confusion, and political machinations that occurred
      among staff led her to develop concepts and theory that elucidate the multilevel
      aspects of the interaction between diversity and power.

PMID- 9231525
TI  - Who treats minorities?
AB  - We studied the characteristics of psychological service providers who treat
      ethnic minority clients in a representative random sample of psychologists listed
      in the National Register of Health Service Providers (NR) in 1986. Ethnic
      minority providers saw more than twice the proportion of ethnic minority clients
      than did non-Latino White providers (24.0% and 11.7%, respectively). Providers
      with cognitive-behavioral clinical/theoretical orientations saw significantly
      more ethnic minority clients than did those with psychodynamic or other
      orientations. Providers with eclectic orientations saw significantly more ethnic
      minority clients than did those with psychodynamic orientations, but eclectic
      providers did not differ from any other provider orientation group. The results
      suggest that more ethnic minority providers are needed and that other providers
      need to increase their ethnic minority clientele.

PMID- 9231526
TI  - Psychiatric symptoms of Hawaiian adolescents.
AB  - The purpose of this study was to examine the interrelationship of depressive
      symptoms with symptoms of anxiety, aggression, and substance abuse in Native
      Hawaiian adolescents. A total of 1,819 Native Hawaiian students were recruited
      from three high schools as part of the initial phase of an ongoing, 4-year,
      longitudinal, cross-sequential study. Psychiatric symptoms were measured with the
      Center for Epidemiological Studies-Depression Scale (CES-D), Spielberger's State
      Anxiety Inventory (SAI), Braver Aggression Dimension Scale (BADS), and Substance
      Abuse Subtle Screening Inventory-Abbreviated (SASSI-A). Scales were standardized
      for this minority population. Depressive symptoms were strongly associated with
      symptoms of anxiety and aggression but only weakly associated with self-reported
      substance abuse. Girls had substantially higher scores than boys on all scales.
      Ninth graders reported more aggressive symptoms than did 12th graders. The
      educational level of the adolescent's main caregiver was not associated with
      symptoms reported in any of the scales. Native Hawaiian adolescents report
      similar symptoms and symptom clusters as do adolescents on the mainland U.S.
      However, Native Hawaiian adolescent girls report a greater number of symptoms in
      all categories when compared to boys. This distinguishes them from most mainland
      adolescent populations.

PMID- 9231527
TI  - Stress, social support, and college adjustment among Latino students.
AB  - This study examined the role of social support and stress on adjustment to
      college among Latino students. Measures of social support, stress, and adjustment
      to college were obtained from 77 Latino college students. Social support was
      positively associated with adjustment and negatively associated with stress. A
      negative relationship was found between stress and adjustment in bivariate
      analyses indicating that exposure to stress interferes with adequate adjustment.
      However, stress did not significantly contribute to adjustment when included with
      social support in multivariate analyses. The functional nature of support was
      also examined in this study. Emotional support was associated with better overall
      and academic adjustment and less stress than instrumental support. there was a
      significant negative relationship between support from friend/other and stress.
      Finally, support from friend/other was negatively correlated with stress from
      exposure to racism. Implications of the study in terms of future research and
      college programs for Latino students are discussed.

PMID- 9231528
TI  - The cultural context of psychology: questions for accurate research and
      appropriate practice.
AB  - This article summarizes the contents of the recent conference, "The Cultural
      Context of Psychology," held in New York City in August 1995. Using an innovative
      format of small-group discussions, 22 facilitators posed a total of over 100 key
      unanswered questions in multicultural psychology. There questions, organized
      along three categories-awareness, knowledge, and skills-form the foundation of
      this article. This article serves as a cognitive map for needed research and
      discussion on multicultural issues in mental health. The references were
      carefully selected to provide the interested reader with resources for follow-up
      work on the topics presented.

PMID- 9231529
TI  - Addressing the repressed needs of the Arabic client.
AB  - In comparison to families in Western society, the traditional Arabic family plays
      a relatively greater role in providing support for adult progeny. This serves to
      condition adult offspring to continue to comply with the will and values of the
      family. Therefore, in exchange for familial support, Arabic individuals learn to
      repress authentic needs and emotions, and within that process they relinquish the
      need for self-actualization. Arabic society discourages individualism and opposes
      self-actualization by means of simultaneous punishment and moralization. Thus,
      there is a relatively greater development of the social value system (or
      superego) and comparatively less development of the self (or ego). In comparison
      to Western society, Arabic individuals continue to experience greater oppression
      during adulthood. Given these cultural differences, the processes of reliving and
      activating repressed needs and emotions, which ultimately serves to promote self
      actualization, will transform intrapsychic conflicts into interpersonal and
      social ones. Thus, personal actions typically encouraged during Western
      psychotherapy are likely to produce significant social oppression. Indeed,
      promoting awareness of repressed needs and emotions often leads the Arabic client
      to become more helpless, because such wishes will rarely be socially sanctioned
      or satisfactorily fulfilled. Therefore, when addressing repressed needs and
      emotions in psychotherapy, ego strength, cultural identity, and degree of
      strictness of the client's family of origin must be considered.

PMID- 9231530
TI  - Constructing common ground: borderland experiences in America.
AB  - Distinguishing among there different versions of diversity, the author provides
      an autobiographical account of a situation in which racial differences were
      treated as mutually enhancing resources. Drawing on additional historical and
      contemporary examples, he suggests that American social "borderlands" are sites
      that encourage and facilitate the flowering of inclusive, multidimensional
      identifies.

PMID- 9231531
TI  - Understanding cross-cultural prognostic variability for schizophrenia.
AB  - Research suggests that critical and negatively charged family environments
      correlate with poor prognosis for schizophrenia across cultures. International
      research also suggests that the increasing industrial status of a country is
      associated with a less favorable outcome for the disorder. This article reviews
      the literature on culture and schizophrenia. An argument is made for using an
      attribution-affect model to help identify factors that may lead to unfavorable
      emotional reactions toward individuals with schizophrenia. In addition, specific
      sociocultural values and beliefs are proposed that are hypothesized to contribute
      to a favorable clinical course for schizophrenia in less industrialized
      countries.

PMID- 9231532
TI  - "Missed, dissed, and pissed": making meaning of neighborhood risk, fear and anger
      management in urban black youth.
AB  - The risk factor, stress engagement, and coping experiences of African American
      youth are not well understood. Given the stressors of racism, hopeless
      perceptions of urban youth, and violence experience and exposure, anger
      experience and expression are reasonable resilient and risky reactions to this
      atmosphere of hostility. This study analyzed the impact upon the anger management
      of adolescents when calamity fears, neighborhood social capital, and kinship
      social support are known. The findings suggest that when the calamity fears of
      youth are high, their anger experience and expression is minimized. This finding
      was prominent for adolescents living in high-risk neighborhoods. Kinship social
      support showed a positive relationship to anger suppression for youth in high
      risk environments. Implications for understanding the phenomenological stress and
      coping experiences of African American youth are discussed.

PMID- 9231534
TI  - Intergroup similarities in judgements of psychiatric symptom severity.
AB  - Researchers have stated that racial/ethnic groups, even if residing in the same
      locale, differ substantially in their judgments of the severity of psychiatric
      symptoms. Severity was defined as the degree to which a symptom would lead to the
      belief that the person manifesting the symptom had some form of mental
      disturbance or psychological problem needing treatment. Research participants
      residing in Hawaii's, varying in sex, age, educational level, and ethnicity,
      rated the severity of 49 psychiatric symptoms. All groups were in close agreement
      with one another in their severity ratings, suggesting that group differences in
      beliefs may be far less than had been claimed.

PMID- 9231533
TI  - Predictors of hostility in a group of relocated refugees.
AB  - The objective of this research was to determine whether early postmigration
      demographic and psychosocial factors associated with cultural marginality would
      predict hostility one decade after flight and relocation. In this longitudinal
      study, participants, who had spent 1 year in a refugee comp, were studied at 1.5,
      3.5, and 9 years postrelocation in the United States (i.e., Times 1, 2, and 3).
      Earlier data were compared with hostility at 9 years. Participants were
      interviewed primarily in their homes, although a few were interviewed elsewhere
      at their request (i.e., community center, University of Minnesota clinical
      offices). The 102 Hmong participants in this study, originally from Laos,
      comprised the first group of Hmong refugees, aged 15 to 72 years old (M = 31.0,
      SD = 13.1), to be relocated from Thailand to Minnesota by the Immigration and
      Naturalization Service in 1976. Hmong research assistants collected these data
      using a questionnaire format at 1.5, 3.5, and 9 years postrelocation. Hostility
      was measured using the Hostility subscale of the 90-item Symptom Checklist (SCL
      90). Female gender, animistic belief, absence of a leadership role, and high
      scores on the SCL-Hostility predicted higher SCL-Hostility scores. Increased
      hostility was associated with greater financial, marital, and mental-emotional
      problems. This study suggests that demographic factors associated with
      marginality and loss of control predict hostility in a group of refugee
      immigrants. Losses and stressors from a decade earlier in Asia did not predict
      hostility.

PMID- 9231535
TI  - Isolated sleep paralysis in African Americans with panic disorder.
AB  - Isolated sleep paralysis (ISP) was assessed in African Americans and Whites
      diagnosed with panic disorder and other anxiety disorders. Participants were
      recruited from an outpatient clinic where they were diagnosed with panic
      disorder, generalized anxiety disorder, obsessive-compulsive disorder, social
      phobia, and simple phobia. Control groups of volunteers without a history of
      psychiatric disorder were included. All research participants completed a
      questionnaire to assess for ISP. Group differences were analysed through a series
      of chi-square analyses. The incidence of recurrent ISP was significantly higher
      in African Americans with panic disorder (59.6%) as compared with African
      Americans with other anxiety disorders (11.1%), African American control group
      participants (23%), Whites with panic disorder (7.5%), Whites with other anxiety
      disorders (0%), and White control group participants (6%). Recurrent ISP was
      found to be more common among African American participants, particularly for
      those with panic disorder. African Americans with panic disorder may experience
      recurrent ISP as a feature of their disorder.

PMID- 9231536
TI  - Parent and family support groups with African American families: the process of
      family and community empowerment.
AB  - This article describes a process of family and community empowerment in which
      psychologists, along with community, school and religious leaders, intervened on
      a multisystemic level and formed a parent and family support group to empower
      families in helping their at-risk adolescents to succeed. The adolescents, who
      were predominantly African American, had been arrested for fighting at school and
      were experiencing academic and behavioral difficulties. Critical incidents in the
      group development and the family and community empowerment process are described.

PMID- 9231537
TI  - Bilingual telephone-assisted computerized speech-recognition assessment: is a
      voice-activated computer program a culturally and linguistically appropriate tool
      for screening depression in English and Spanish?
AB  - The purpose of this study was to evaluate an automated voice-interactive program
      for screening depression in English and Spanish. The Center for Epidemiological
      Studies-Depression Scale (CES-D) was administered in two interview formats: a
      speech recognition program presented by cellular telephone, and a face-to-face
      method. In a single-session counterbalanced design, 32 English speakers and 23
      Spanish speakers completed randomly ordered administrations of the two CES-D
      methods, the Beck Depression Inventory (BDI), and the Short Acculturation Scale
      (SAS). There was strong evidence that the two CES-D methods were psychometrically
      equivalent, reliable, and valid in both languages. The two methods were highly
      rated by both language groups. The Spanish speakers did not display a preference
      for either method, but the English speakers preferred the face-to-face method.
      The results also suggested that verbal response latency time was positively
      correlated with depression scores. Last, the Spanish-speakers' acculturation
      levels were not correlated with depression scores. Differences in age, education,
      and income between the language groups were confounded by unequal sample sizes.
      The findings generally supported the viability of the automated CES-D as a
      culturally and linguistically appropriate tool for screening depression in
      English and Spanish. Furthermore, the analyses of respondent voice
      characteristics show promise as a method for screening depression in both
      languages.

PMID- 9231538
TI  - Cognitive testing with culturally diverse children.
AB  - This special section discusses how the psychological status of minority children
      can be enhanced if psychologists adopt an integrated approach in establishing
      linkages and in examining interactions and reciprocal effects when assessing
      ethnically, linguistically, and culturally different children. Implications for
      conducting culturally relevant assessments of intelligence are discussed. A
      bioecological model for incorporating these suggested techniques into a program
      evaluation is suggested.

PMID- 9231539
TI  - The cognitive assessment of limited-English-proficient children: current problems
      and practical recommendations.
AB  - Children from limited-English-proficient backgrounds are frequently assessed for
      the purposes of classification, educational placement decisions, and intervention
      planning. Problems inherent in the process of identifying their intellectual
      strengths and weaknesses are discussed, including questionable special education
      referrals, the use of English as the language of testing, the use of
      interpreters, the administration of normed tools, and the use of translated
      tests. Among the practical recommendations explored are prereferral activities,
      assessment of language dominance and proficiency, training of bilingual
      personnel, the integration of multiple assessment tools, adaptation of available
      measures, and alternative assessment models.

PMID- 9231540
TI  - Bio-ecological approach to cognitive assessment.
AB  - Because determining a child's educational program usually takes into
      consideration the child's cognitive functioning, it is vital that those who are
      involved in this enterprise recognize that many variables contribute to and
      explain performance. Thus, careful consideration, assessment, and planning are
      mandatory to plan a child's individual educational program. This article
      emphasizes that cognitive assessment is both a formal and an informal process
      that occurs in several contexts-the school, the home, and the community.
      Therefore, when psychological evaluators assess the cognitive performance of a
      child, it is necessary to analyze the complete of his or her social/emotional
      environments that have contributed to his/her current cognitive performance
      levels. Thus, it is vital to examine the orientation of family members, the
      academic assistance students receive at home, as well as the current and previous
      classroom environments in which the student has been educated. Six
      nonpsychometric measures (using item equivalency, test-teach-retest, and
      contextualization) were developed by the authors and are presented in recognition
      that there are many factors that one must consider when interpreting the
      performance of a child.

PMID- 9231542
TI  - Ostial lesions of the left anterior descending coronary artery: should we
      balloon, atherectomize, stent, rotablate, synergise or graft?

PMID- 9231541
TI  - A bio-ecological case study: a Caribbean child.
AB  - The present article presents how the bio-ecological assessment system is applied
      in assessing a child's cognitive intelligence beyond a psychometric intelligence
      test. The recognition that there are many types of intelligence, such as musical
      and bodily kinesthetic, is exemplified. The case presented is that of a child
      with deficient cognitive functioning on the psychometric tests, but advanced
      functioning on the "Other Intelligence Assessment Measure." Diagnostic
      impressions are given and implications for report writing and interventions are
      suggested.

PMID- 9231543
TI  - Selection of optimal pacing mode.

PMID- 9231544
TI  - Improvement in contractility of infarct zone after dobutamine infusion predicts
      good (TIMI II or III) flow in infarct related artery.
AB  - Eighteen patients of 'Q' wave acute myocardial infarction (AMI) (age 50 +/- 6.2
      years), underwent dobutamine stress echocardiography (DSE) before hospital
      discharge (7.2 +/- 1.3 days after AMI) to find out the correlation between
      response of infarct zone to dobutamine infusion and TIMI grade flow in infarct
      related artery (IRA). The aim of study was to test the hypothesis that infarct
      zone which shows improvement in contractility after dobutamine infusion has
      viable myocardial tissue and would have good flow (TIMI II or III) in IRA.
      Echocardiographically, improvement in contractility in the centre of infarct zone
      by at least 1 grade (on a scale of 4) was termed as positive response on DSE. The
      mean dose of dobutamine was 19.4 micrograms/kg/min. Ten patients had positive
      response on DSE; 8 of them had good antegrade flow in IRA. Eight patients had no
      improvement in contractility of infarct zone on DSE; 6 of them had poor flow in
      IRA. Clinical markers of reperfusion (relief of chest pain, early ST settlement,
      peak CPK-MB levels), age of patient, site of AMI, time to thrombolysis, resting
      left ventricular ejection fraction, wall motion score of the infarct zone and
      presence of collaterals were not significantly different in patients with good or
      poor flow in IRA. Thus, improvement in contractility of infarct zone after
      dobutamine infusion can predict good flow (TIMI II or III) in IRA with 80 percent
      sensitivity, 75 percent specificity, 80 percent diagnostic accuracy, 80 percent
      positive predictive value and 75 percent negative predictive value.

PMID- 9231545
TI  - Study of HLA-A, B, C, DR, DQ profile of patients with established rheumatic heart
      disease in Kashmir.
AB  - This study included 54 unselected patients with rheumatic heart disease (RHD)
      with or without history of rheumatic fever and 224 control subjects, all
      Kashmiris. HLA-A19 was increased in 42.59 percent of patient population as
      against 23.66 percent of controls, with a relative risk of 2.39. HLA-DR4 was
      positive in 56 percent of patients as against 31.69 percent in controls with a
      relative risk of 2.74. DQ3 was also present in 72 percent of patient population
      as against 50.7 percent of controls. These findings suggest a genetic
      predisposition to rheumatic fever/RHD. More family studies are warranted.

PMID- 9231546
TI  - Age and intrinsic left ventricular myocardial contractility.
AB  - The purpose of this study was to compare the left ventricular (LV) intrinsic
      contractile function in normal elderly (age > or = 60 years, mean age 66 +/- 4
      years) and young (age < or = 35 years, mean 27 +/- 9 years) healthy volunteers by
      stress-shortening and stress-length relationship using a co-variate analysis.
      Echocardiographically determined meridional and circumferential wall stress were
      plotted against LV fractional shortening, velocity of circumferential fibre
      shortening, end-systolic volume and diameter. LV ejection fraction, preload
      (denoted by end-diastolic volume) and afterload (expressed as circumferential
      wall stress) were similar in the two groups. Stress-shortening and stress-length
      relationships using the circumferential wall stress showed no difference in the
      two groups, although meridional wall stress was greater in the elderly
      population. Our results suggest that circumferential wall stress is a better
      method to detect intrinsic contractile abnormality in the elderly. Intrinsic LV
      ejection performance is within the normal range in the elderly healthy
      individuals.

PMID- 9231547
TI  - Comparison of clinical outcome of fixed-dose subcutaneous low molecular weight
      heparin (tinzaparin) with conventional heparin in unstable angina: a pilot study.
AB  - Forty patients who were hospitalized for unstable angina were randomized to
      receive treatment with either regular heparin (Group I) in conventional dose as
      continuous infusion for 5 days or fixed-dose low molecular weight heparin (LMWH)
      (Group II), 3500 units subcutaneous twice daily for a period of 5 days. Both the
      groups were evenly matched with regard to age, sex presence of risk factors and
      adjunctive drug therapy. The clinical endpoints at the end of 5 day therapy were:
      recurrence of angina, occurrence of myocardial infarction and need for urgent
      revascularization. In Group I, 6 out of 20 patients had recurrence of angina, of
      whom 3 required urgent coronary angiography and revascularization. In Group II, 4
      out of 20 patients had recurrence of angina, of whom one patient required urgent
      angiography and angioplasty. There were no bleeding complications in either of
      the groups. The recurrent anginal episodes in the conventional heparin group
      correlated with low aPTT values at the time of angina. Thus, this pilot study
      suggests that LMWH is equally effective in the treatment of unstable angina, the
      advantage of LMWH being the ease of administration and no need for monitoring
      aPTT levels during therapy.

PMID- 9231548
TI  - Elective coronary stenting after recanalization for chronic total occlusion:
      clinical and angiographic follow-up results.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) for chronic totally
      occluded coronary arteries is associated with a significant residual stenosis and
      a high incidence of restenosis. Between March 1995 to February 1997,
      recanalization of chronic total occlusion (CTO) was attempted in 95 patients, of
      whom 79 (83.1%) were dilated successfully using balloon angioplasty, rotablation
      or both. Forty two patients underwent elective stent implantation to evaluate the
      influence of stenting on immediate results and clinical as well as angiographic
      outcome on long-term follow-up. There were 39 males and 3 females, with a mean
      age of 51 +/- 8 years. The majority (69.1%) had multivessel disease. The target
      vessel was LAD in 25 (58.1%), RCA in 12 (27.9%), LCx-OM in 5 (11.6%) and ramus in
      1 (2.3%). After recanalization and adequate predilatation, various types of
      stents were deployed successfully at the target site in all patients, using high
      pressure intrastent balloon dilatation. The luminal diameter stenosis reduced to
      47 +/- 15 percent after balloon angioplasty and < 10 percent in all, after stent
      implantation. There were no in-hospital major complications, including subacute
      stent thrombosis, myocardial infarction, need for emergency bypass graft surgery
      or death. The follow-up data is available in 36 patients, ranging from 1-22
      months (mean: 7.4 +/- 4.7; median: 6). Of these, 32 (88.8%) were free of angina
      at their last visit, 3 (8.3%) required target lesion revascularization and 2
      patients died, one at 3 weeks and the other at 6 months after the procedure. The
      event-free survival, estimated by the Kaplan-Meier survival curve was 97.3, 82.8
      and 77.25 percent at one, 6, and 12 months, respectively after stenting. Out of
      29 eligible patients, 20 underwent repeat coronary angiography after 6 months,
      which revealed restenosis in 5 (25%). In conclusion, our study shows that
      elective coronary stenting following successful recanalization of chronic total
      occlusion produces an excellent immediate result and reduces the recurrence of
      angina, target lesion revascularization and angiographic restenosis on long-term
      follow-up.

PMID- 9231549
TI  - Coronary artery stenting in acute myocardial infarction.
AB  - Little information is available on the use of coronary stents to treat suboptimal
      results during direct angioplasty in acute myocardial infarction (AMI). In this
      study, we report 16 cases of AMI who underwent stent implantation in infarct
      related artery for suboptimal results and their 6 months angiographic follow-up.
      Immediate angiographic success was achieved in all patients. The minimal luminal
      diameter increased from 0.06 +/- 0.12 mm to 2.89 +/- 0.12 mm (p < 0.001). One
      patient died in the hospital on day 8 due to subacute stent thrombosis. No
      patient required emergency bypass surgery. Two patients required blood
      transfusion for groin haematoma and one required intracoronary thrombolysis. All
      patients underwent exercise stress test at 1 month and at 3 months and coronary
      angiography at 4 months or earlier it indicated. At the end of 6 months follow
      up, 4 patients had a positive exercise test and coronary angiography revealed
      angiographic restenosis in 3 and progression of disease in other vessels in 1
      patient. We conclude that stent deployment is a viable option to treat suboptimal
      results after direct angioplasty in AMI.

PMID- 9231550
TI  - Anaesthetic management of patients undergoing surgery for tachyarrhythmias.
      Initial experience with 16 patients.
AB  - Sixteen patients suffering from various cardiac arrhythmias were treated
      surgically. Intraoperative computerised electrophysiologic mapping was used in
      14. Thirteen patients were suffering from Wolff-Parkinson-White syndrome. They
      underwent surgical division or cryoablation of accessory pathways. Two patients
      who had rheumatic mitral stenosis with left atrial clot underwent "Maze III"
      procedure with open mitral commissurotomy and clot removal. One patient with
      paroxysmal refractory ventricular tachycardia and a left ventricular aneurysm had
      an aneurysmectomy with subendocardial resection of the arrhythmic focus. All
      antiarrhythmic medications were discontinued preoperatively. Morphine was the
      principal anaesthetic agent, supplemented with halothane. Muscle relaxation was
      provided with pancuronium bromide. The various problems encountered included
      hypotension and arrhythmia during placement of epicardial band array for mapping
      (4 patients), ventricular tachycardia during internal jugular vein cannulation (1
      patient) and continuance of delta wave after cryoablation in 2 patients.
      Halothane may have interfered with electrophysiologic mapping and accurate
      localization of accessory pathway leading to persistence of delta wave. The
      choice of anaesthetic agents should be guided by the electrophysiologic effects
      and potential influence of these agents on the accessory pathways.

PMID- 9231552
TI  - Coronary embolism in a patient with mitral prosthesis treated by coronary
      angioplasty--a case report.

PMID- 9231551
TI  - Myocardial infarction following electric shock.

PMID- 9231553
TI  - Isolated right atrial infarction in a patient with corpulmonale. A
      clinicopathological report.

PMID- 9231554
TI  - Palliative blade-balloon atrial septostomy in primary pulmonary hypertension.

PMID- 9231555
TI  - Percutaneous coil embolization of coronary to pulmonary arterial fistula in a
      forty-six year old patient.

PMID- 9231556
TI  - Self-expanding wallstent for management of severe abdominal coarctation due to
      non-specific aortoarteritis.

PMID- 9231557
TI  - Enalapril-induced renal artery thrombosis in unilateral renal artery stenosis.

PMID- 9231558
TI  - Radiofrequency ablation of an unusual variant of atrial flutter.

PMID- 9231559
TI  - Radiofrequency catheter ablation of accessory pathways in association with
      congenital heart disease.

PMID- 9231560
TI  - Single lung Rastelli repair.
AB  - A four year old severely cyanotic child was diagnosed to have double outlet right
      ventricle, large subpulmonic ventricular septal defect, severe pulmonic valve
      stenosis with absent left pulmonary artery and bilateral superior vena cavae
      without any connecting vein. A Rastelli type repair was performed utilizing the
      right pulmonary artery as the only run-off for the right ventricle. Immediate
      post-pump right ventricular (RV) pressures were 90 percent of the systemic. Six
      months later, echocardiographically estimated RV pressure was 60 percent of the
      systemic. The child is doing well at 6 months follow-up.

PMID- 9231561
TI  - Pleuro-pericardial communication: demonstration by pleural contrast
      echocardiography.

PMID- 9231563
TI  - Ethics of authorship of scientific papers.

PMID- 9231562
TI  - A new system of classification and nomenclature for coronary artery disease
      subsets.

PMID- 9231565
TI  - Limitation of computerized averaging of ECG during stress testing.

PMID- 9231564
TI  - National PTCA registry of India data for 1996.

PMID- 9231566
TI  - Association of cardiomyopathy with welding.

PMID- 9231567
TI  - Coronary artery disease in South Asians.

PMID- 9231568
TI  - Education in geriatric psychiatry.
AB  - The UK has seen many significant developments during the last 30 years in
      geriatric psychiatry, with emphasis on multi-disciplinary working and on the
      integration of services for the elderly. Accompanying these changes has been a
      growing public consciousness of the psychiatric disorders of later life and of
      the needs of old people and their carers. With a huge increase this century in
      the proportion of very elderly people, care of the elderly has achieved greater
      recognition in the medical training of both generalists and specialists. Greater
      emphasis also is being given to gerontology, both social and biological. In this
      paper the authors examine recent developments in medical education in the UK and
      show how changing approaches to medical training are shaping developments in
      geriatric psychiatry education. They describe recent innovations in both teaching
      styles and assessment methods and consider how developments in Computer Aided
      Learning can be applied to the teaching of geriatric psychiatry.

PMID- 9231569
TI  - History of geriatric psychiatry in Israel.
AB  - This article describes the history of a relatively new branch in Israel's
      psychiatry, geriatric psychiatry. The unique features of Israel are described: a
      young country with an ancient history, uninterrupted migration waves, including
      the elderly strata, the reactivation of traumatic experiences in elderly
      Holocaust survivors and the impact of the security situation in particular on the
      elderly population. There is a growing awareness of the importance of geriatric
      psychiatry, in connection with the above features, with a quite rapid development
      of this branch in the country. Developing services are described, as are research
      projects and the contribution made by Israel's geriatric psychiatrists in the
      development of the field.

PMID- 9231570
TI  - Psychopathology in dementia.
AB  - The purpose of this overview is to describe the psychological and behavioral
      symptoms of dementia reported in the professional literature in recent years.
      This subject, a relatively neglected one, is considered in order to focus
      attention on a number of the symptoms most troublesome to the demented person's
      surroundings which lead to his/her hospitalization, with all the implications
      this has on the patients, their families and the community's health budget. To
      carry out an early and effective intervention, professionals need to define and
      recognize these symptoms and gain experience in treating them, either by
      intervention in the environment or by medication. This survey attempts to examine
      the state of the art in this field, while analyzing the difficulties that emerge
      in studying it.

PMID- 9231571
TI  - "Failure to thrive" in elderly depressed patients: a new concept or a different
      name for an old problem?
AB  - With increasing frequency one may encounter the term "failure to thrive (FTT)" as
      applied to elderly patients. FTT in elderly patients is characterized by an
      insidious deterioration in their self-care abilities, loss of weight, loss of
      interest in social activities, a gradual decline in physical and/or cognitive
      function, and increased dependency on family members. The deterioration is beyond
      the expected, age-associated, "normal" decline. Depression is considered to be
      only one of the possible causes of FTT in the elderly. However, we suggest that
      the term, "FTT," as applied to elderly, depressed patients, does not appear to
      have intrinsic clinical value in that it describes a situation which represents
      an extreme form of the depressed syndrome rather than a separate clinical entity.
      It seems that early recognition of FTT would lead to appropriate supportive
      treatment being instituted before an advanced level of deterioration is reached.
      However, early diagnosis of the depression should have the same result and should
      lead to appropriate antidepressant treatment combined with vigorous nutritional
      intervention as well. The clinical problem which may lead to a delay in treatment
      of "FTT" affected elderly depressed patients is not a failure to diagnose "FTT"
      but a failure to diagnose depression.

PMID- 9231572
TI  - Length of hospitalization and disposition of elderly vs younger delirium patients
      in psychiatric hospitals.
AB  - Although it is commonly accepted that delirium patients require the full
      facilities of general hospitals, practical experience has shown that delirium
      patients of all ages continue to be admitted to psychiatric institutions. The
      present study was designed to detect any differences in the length of
      hospitalization and disposition (discharge back to the community, transfer to a
      general hospital, death during the index hospitalization, transfer to another
      psychiatric hospital) between elderly (> 65 years) and younger delirium patients
      admitted to psychiatric hospitalization. Our hypothesis was that the prognosis
      (represented in this study by the above-mentioned measures) of elderly delirium
      patients in a psychiatric hospital would be poorer compared with younger delirium
      patients. We studied psychiatric case register data of 805 patients with delirium
      admitted to psychiatric hospitals during the period 1984-1993. Our sample was
      divided into four ICD-9-CM categories: delirium in dementia, delirium tremens
      (DT), drug-induced delirium, and acute and subacute delirium. No significant
      differences in the length of hospitalization were found between < 65- and > 65
      year-old patients in the categories studied. There were disposal differences
      between the two age groups in the acute and subacute delirium parameters, but
      findings in the other categories were similar. Practical implementation of the
      results in terms of appropriate place of management of delirium patients in a
      psychiatric hospital is discussed.

PMID- 9231573
TI  - Recurrent toxic delirium in a patient treated with SSRIs: is old age a risk
      factor?
AB  - We present the case of a 71-year-old female suffering from bipolar affective
      disorder type 2 and an old lacunar brain infarct who, under the combined
      treatment of fluoxetine for depression and low dose trazodone for the
      accompanying insomnia, developed a toxic delirium. The subject presented with
      mental state changes (confusion and agitation), hyperreflexia, diaphoresis,
      nausea, vomiting, fever, and a general tonic-clonic seizure which developed soon
      after an increase in the trazodone dose. One year prior to the above episode, she
      was hospitalized for a transient episode of agitated confusion while being
      treated with fluvoxamine for depression, alprazolam and brotazolam for the
      accompanying anxiety and insomnia. Both episodes subsided spontaneously when
      treatment was discontinued. This case reports the possible existence of increased
      vulnerability to hyperserotonergic states in elderly patients suffering from
      concomitant psychiatric and neurological disorders.

PMID- 9231574
TI  - Primary hyperparathyroidism: neuropsychiatric manifestations and case report.
AB  - We describe an elderly patient with primary hyperparathyroidism and dementia who
      was admitted to a psychogeriatric department because of delusions of new onset.
      While hospitalized he had three episodes of delusions that coincided with mild
      hypercalcemia. Treatment for the hypercalcemia resulted in rapid remission of the
      delusional state, but did not induce any change in his cognitive abilities or in
      the severity of dementia. We review the relevant literature and offer
      recommendations for treatment and follow-up of elderly patients with
      hyperparathyroidism associated with a delusional state.

PMID- 9231575
TI  - Social and psychological adjustment of Soviet-born and Israeli-born adolescents:
      the effect of the family.
AB  - This study examined the impact of family functioning on the educational, social
      and emotional behavior of Soviet-born and Israeli-born adolescents in Israel. The
      parents of the Israeli-born adolescents were born in Russia; thus, this study
      controlled for their national background. The results showed that the two groups
      were similar in their perception about the way their families function. Both
      groups perceived that social and psychological well-being among adolescents were
      significantly related to family functioning. Multivariate analysis revealed that
      family functioning was the major factor predicting the level of self-esteem and
      peer relationships among adolescents, as well as a myriad of psychological
      symptoms. Directions for future research are discussed.

PMID- 9231576
TI  - Suicide ideation among recent immigrants: an epidemiological study.
AB  - This paper reports preliminary results of an epidemiological survey of suicide
      ideation among recent adult immigrants from the former Soviet Union to Israel.
      The study presents one-month prevalence rates of suicide ideation, and the
      relationship of suicide ideation with demographics, self-rated psychological
      distress, depression, emotional isolation and social support. Results show that
      the one-month prevalence rate of suicide ideation in the population is 16.9%.
      Suicide ideation was most frequent among socially and emotionally isolated
      immigrants with lower social support. The strongest predictor of suicide ideation
      for both sexes was level of psychological distress, whereas the severity of
      depression predicted suicide ideation only in females. The findings can be used
      as a point of departure for the development of suicide prevention programs.

PMID- 9231577
TI  - Jews and their intraethnic vulnerability to affective disorders, fact or
      artifact? II: Evidence from a cohort study.
AB  - This paper, which complements a prior review of published studies, reports
      findings from a community-based survey of 4,914 Israel-born offspring of
      immigrants from Europe (Ashkenazim) and North Africa. Respondents were examined
      by psychiatrists using the Schedule for Affective Disorders and Schizophrenia,
      Israel version, and diagnosed with the Research Diagnostic Criteria. Unlike
      previous studies, this investigation found that Israelis of North African origin
      had significantly higher rates of affective disorders, including major depressive
      and intermittent depressive disorders. The Ashkenazim, however, had higher rates
      of bipolar I disorder at the definite level of diagnosis. Differential patterns
      in help-seeking may account for the divergent findings between this community
      based study and earlier treatment-based reports. These results suggest the need
      to further investigate social and genetic etiological factors that may explain
      the differential rates.

PMID- 9231578
TI  - Domestic social integration and suicide in Israel.
AB  - In time-series studies of Israeli suicide rates from 1960 to 1989, male and
      female suicide rates were positively associated with marriage rates. Divorce
      rates were positively associated with male suicide rates but negatively with
      female suicide rates, while the pattern for the association between birth rates
      and suicide rates was reversed. These results were not as consistent with
      predictions from Durkheim's theory of suicide as were the results from the USA
      for the same time period.

PMID- 9231579
TI  - The influence of sociopolitical events on the content of delusions.

PMID- 9231580
TI  - Prolegomena to a declaration.

PMID- 9231581
TI  - Advance directives affecting medical treatment choices.
AB  - Advance directives theoretically enhance individual autonomy and facilitate
      treatment decision making at the end of life. There is little empirical evidence
      to support this, however. Based on a national postal survey of 2172 randomly
      selected medical practitioners (response rate 73%), this paper examines the
      effect advance medical directives have on (a) treatment prescribing for
      terminally ill people and (b) the degree of difficulty practitioners experience
      in making treatment choices. A hypothetical patient with Alzheimer's disease and
      an acute life-threatening illness was presented with and without an advance
      directive. With a directive, respondents were more uniform in their choice of
      treatment, with 86% choosing as the patient had requested. Difficulty with
      decision making was also less with the directive, 31% vs 45% with no directive.
      The data indicate that advance directives do affect practitioners' treatment
      choices in favor of patient wishes and reduce the difficulty practitioners may
      experience in making them.

PMID- 9231583
TI  - Physician perspectives on unconventional cancer therapies.
AB  - The popularity of unconventional therapies has grown dramatically in recent
      years. This paper reports on the results of a pilot study investigating the
      perspectives of physicians involved with cancer care regarding their reactions to
      this trend and their ways of trying to meet associated challenges. Nine
      oncologists, nine general practitioners, and one surgeon were interviewed over
      the telephone, employing open-ended questions. The physicians were unanimously
      interested in having information available about unconventional therapies. They
      also expressed a desire to be supportive of patient choices in this area,
      provided conventional therapy was not compromised. However, there was little
      interest in initiating communication about unconventional therapies, with most
      seeing such discussions as a poor use of their time. Suggestions for future
      research, as well as educational and policy strategies, are addressed.

PMID- 9231582
TI  - Multicentre study on the prevalence of symptoms and symptomatic treatment in HIV
      infection. Central Italy PRESINT Group.
AB  - We investigated the prevalence and intensity of symptoms and the use of drugs for
      symptom control among all HIV-infected patients reporting to the outpatient
      clinics or wards of 15 clinical centres in central Italy, recording clinical and
      epidemiological data on three consecutive days. A total of 1128 patients were
      observed and tabulated. Their most frequent symptoms were asthenia (65%),
      anorexia (34%), cough (32%), pain (29%), and fever (29%). Opioid analgesics were
      used in 3% of these patients and non-opioid analgesics in 13%. A large majority
      of HIV-infected patients presented with symptoms regardless of the stage of their
      disease. Pain was present in fewer than one third of patients but nonetheless
      seemed to be undertreated. Pain was more frequent and more intense among
      intravenous drug users. Based on our study, a greater effort to control symptoms
      in HIV patients seems to be warranted.

PMID- 9231584
TI  - A way to screen for suffering in palliative care.
AB  - We report a new tool for screening the suffering of terminally ill patients in a
      palliative care service. We systematically asked 371 terminal oncological and
      AIDS patients on 665 different occasions, "How long did yesterday seem to you?";
      we then asked them to assess their current condition. The simple answer about
      subjective length of time correlated well with subjective suffering in
      approximately half the patients. Thus it may be a good starting point for future
      assessment and more extensive explorations.

PMID- 9231585
TI  - Development and evaluation of a protocol to manage fecal incontinence in the
      patient with cancer.
AB  - Fecal incontinence is an important yet often overlooked clinical problem in the
      care of patients with cancer. This paper presents a protocol for the assessment
      and management of this distressing symptom. The objective of the protocol is to
      regulate bowel motion, thereby minimizing fecal incontinence and improving
      patients' physical functioning, self-esteem, dignity, and quality of life. A
      comprehensive assessment addressing the patient's physical status, previous
      elimination routines, dietary habits, and medications provides the foundation for
      successful management. Components of the intervention include dietary
      modification, pharmacotherapy with laxatives and suppositories, and attention to
      routines that capitalize on the normal, involuntary gastrointestinal reflexes.
      Promotion of normal bowel elimination patterns, positioning, and comprehensive
      patient teaching and support are also critical components of the intervention.
      Our experience with this protocol and the outcomes achieved in a small series of
      patients are discussed.

PMID- 9231587
TI  - "Alan".

PMID- 9231586
TI  - Data collection as the first step in program development: the experience of a
      chronic care palliative unit.
AB  - This retrospective descriptive study of 73 patients who died in St. Peter's
      Hospital examines and contrasts the patients profile and referral sources of a
      palliative care unit in a chronic care hospital over two six-month periods during
      1994 and 1995. Shortened length of stay (83.8 and 43.2 days respectively),
      documentation issues, CPR practices (CPR was desired by seven patients up to the
      time of death), and lack of referrals from long-term care facilities have led St.
      Peter's Hospital to ask further questions of its palliative care program, e.g.
      given the lack of referrals from long-term care facilities, how is palliative
      care being managed in this sector? In Ontario, palliative care has been placed
      under the domain of chronic care and program development depends in part on the
      knowledge of the population it serves. This study is a first step.

PMID- 9231588
TI  - A continuum of palliative care services: reflections on an Australian model of
      care.

PMID- 9231589
TI  - Trigeminal neuralgia managed by a change in lifestyle.

PMID- 9231590
TI  - Successful multidimensional intervention in a patient with intractable
      neuropathic cancer pain.

PMID- 9231591
TI  - Opportunity to present our observations and opinions on slow euthanasia.

PMID- 9231592
TI  - An oversupply in the offing?

PMID- 9231593
TI  - When to remove a tooth.

PMID- 9231594
TI  - Reader's Digest.

PMID- 9231595
TI  - Reader's indigestion.

PMID- 9231596
TI  - Mixed messages?

PMID- 9231597
TI  - Treatment decision making.

PMID- 9231598
TI  - New uses for tetracyclines.

PMID- 9231599
TI  - Emergency medicine: beyond the basics.
AB  - Medical emergencies can arise in the dental office. Preparedness for these
      emergencies is predicated on an ability to rapidly recognize a problem and to
      effectively institute prompt and proper management. In all emergency situations,
      management is based on implementation of basic life support, as needed. The
      author describes the appropriate management of two common emergency situations:
      allergy and chest pain.

PMID- 9231600
TI  - Fluoride concentrations of infant foods.
AB  - Infants who ingest high amounts of fluoride can be at risk of dental fluorosis.
      The authors analyzed the fluoride concentration of 238 commercially available
      infant foods. Fluoride concentrations ranged from 0.01 to 8.38 micrograms of
      fluoride per gram, with the highest fluoride concentrations found in infant foods
      containing chicken. Infant foods, especially those containing chicken, should be
      considered when determining total fluoride intake.

PMID- 9231601
TI  - Assessing the cariogenic potential of some infant formulas, milk and sugar
      solutions.
AB  - Using a desalivated rat model, the authors found that several commonly used
      infant formulas had significant cariogenic potential. Sucrose was by far the most
      cariogenic and cows' milk the least cariogenic of all the products examined. The
      data show that dental practitioners and other health care professionals should
      discourage the use of sugar in baby bottles and provide information on which
      formulas are least likely to induce caries when continuous bottle feeding is
      unavoidable.

PMID- 9231602
TI  - Use of panoramic radiography among an ambulatory dental population to detect
      patients at risk of stroke.
AB  - Panoramic radiographs of 3.6 percent of 1,175 newly accepted dental school
      patients displayed calcifications in the area of the carotid vasculature. The
      authors interviewed the patients with calcifications to determine whether they
      exhibited any recognized atherosclerosis, risk factors. One patient had symptoms
      of atherosclerosis, and a statistically significant correlation was found for
      obesity among the patients interviewed. The authors concluded that panoramic
      radiography is useful for identifying some asymptomatic patients with carotid
      calcifications. These patients should be referred to their physicians promptly
      for a cerebrovascular work-up as part of an active stroke-prevention strategy.

PMID- 9231603
TI  - Guided tissue repair of complete buccal dehiscences associated with periapical
      defects: a clinical retrospective study.
AB  - Apical surgery can enhance the success of restoring certain endodontically
      treated teeth. New regenerative surgical modalities, with emphasis on guided
      tissue regeneration, or GTR, have expanded clinicians' ability to retain teeth
      that previously were considered to be beyond restoration. The retrospective
      clinical study described in this article demonstrates that the use of GTR without
      the use of allograft demineralized bone achieves regeneration that is clinically
      and radiographically indistinguishable from the surrounding bone. The author
      presents the indications and contraindications for case selection, surgical
      management and postoperative findings for this treatment option.

PMID- 9231604
TI  - Comparing prospective and retrospective evaluations of temporomandibular
      disorders after orthognathic surgery.
AB  - The authors conducted a study to document agreement between prospective
      examinations performed by trained clinical trial examiners and retrospective
      surgical chart reviews in identifying signs and symptoms of temporomandibular
      disorders, or TMD. Only a small fraction of the signs and symptoms identified by
      clinical trial examiners were documented in the surgical charts. Studies relying
      on retrospective chart reviews may seriously underestimate signs and symptoms of
      TMD.

PMID- 9231605
TI  - Advisory statement. Antibiotic prophylaxis for dental patients with total joint
      replacements. American Dental Association; American Academy of Orthopaedic
      Surgeons.
AB  - An expert panel of dentists, orthopaedic surgeons and infectious disease
      specialists convened by the American Dental Association and the American Academy
      of Orthopaedic Surgeons, or AAOS, performed a thorough review of all available
      data to determine the need for antibiotic prophylaxis to prevent hematogenous
      prosthetic joint infections in dental patients who have undergone total joint
      arthroplasties. The result is this report, which has been adopted by both
      organizations as an advisory statement. The panel's conclusion: Antibiotic
      prophylaxis is not indicated for dental patients with pins, plates and screws,
      nor is it routinely indicated for most dental patients with total joint
      replacements. However, it is advisable to consider premedication in a small
      number of patients who may be at potential increased risk of hematogenous total
      joint infection.

PMID- 9231606
TI  - Multirooted anomalies in the primary dentition of Native Americans.
AB  - The dental literature contains a small number of reports of primary multirooted
      anomalies and even fewer reports on the clinical significance of these findings.
      When conducting routine clinical examinations, the authors found multirooted
      anomalies in three Native American children. The anomalies included a primary
      bifurcated maxillary left canine, a primary three-rooted mandibular right first
      molar and bilateral primary three-rooted mandibular first and second molars. The
      clinical significance of these types of anomalies is discussed.

PMID- 9231607
TI  - Achieving tight contacts in Class II direct resin restorations.

PMID- 9231609
TI  - Sex, enamel and forensic dentistry: a search for identity.

PMID- 9231608
TI  - Body piercing involving oral sites.
AB  - The authors present a case report on body piercing involving oral sites. Common
      locations and types of oral jewelry and piercing techniques are discussed. Oral
      considerations of intraoral piercing are emphasized.

PMID- 9231610
TI  - What category of impression material is best for your practice?

PMID- 9231611
TI  - Patient rights, provider rights: balancing the conflict.

PMID- 9231612
TI  - Circumcision. Could we all get on the same page please.

PMID- 9231613
TI  - 1997 legislative wrap-up.

PMID- 9231614
TI  - Neonatal circumcision: anatomic contraindications.
AB  - Complications from neonatal circumcision may result from inexperience or poor
      technique, but may also result from poor patient selection based on penile
      anatomy. The anatomic contraindications to neonatal circumcision are therefore
      presented in an effort to prevent complications.

PMID- 9231615
TI  - Total facility evacuation at Helena Regional Medical Center.

PMID- 9231617
TI  - The effects of hypokalemia on the heart.

PMID- 9231616
TI  - Retrograde extension of a chronic type III aortic dissection.

PMID- 9231618
TI  - Hepatitis C--a threat to public health.

PMID- 9231619
TI  - HIV in Arkansas.

PMID- 9231620
TI  - Radiological case of the month. Gallstone ileus.

PMID- 9231621
TI  - ECG of the month. On the fast or slow lane? Narrow-QRS tachycardia.
AB  - The continuous rhythm strip shown below, limb lead II, belongs to a 37-year-old
      woman. She has a long-standing history of palpitations, for which she has been
      hospitalized many times. She is not compliant with treatment.

PMID- 9231622
TI  - Cystic hygromas of the head and neck.
AB  - Cystic hygroma is a congenital lymphatic malformation with a predilection for the
      head and neck and that usually presents in the pediatric population. This is a
      benign lesion but is often challenging to deal with. This paper reviews some of
      the characteristic features of this lesion including its presentation,
      pathophysiology, evaluation, and treatment.

PMID- 9231623
TI  - Radiology case of the month. Knee pain: intra-articular mass. Pigmented
      villonodular synovitis (PVNS).

PMID- 9231624
TI  - The journal 100 & 150 years ago. New Orleans Medical and Surgical Journal. July
      1847 & 1897.

PMID- 9231625
TI  - Liver transplantation: perspectives after 250 liver transplants at the Ochsner
      Clinic.
AB  - At the Ochsner Clinic we recently performed our 250th liver transplant. Reaching
      this milestone has led us to reflect back on the history of liver transplant,
      both at our own institution and nationally, noting the many achievements and
      improvements in liver transplantation during the relatively brief history of this
      therapeutic modality. Furthermore, there are a number of issues both medical and
      political which will likely be affecting how liver transplantation is performed
      in the future.

PMID- 9231626
TI  - Renal biopsy in a child with nephrotic syndrome.
AB  - A 6-year-old girl with nephrotic syndrome was treated with prednisone, without
      response. A renal biopsy was obtained. Following the format used at the Tulane
      Renal Biopsy Conferences, the clinical presentation, differential diagnosis and
      clinical discussion in this young patient will be presented first. The second
      part will include the renal biopsy findings, the final diagnosis and the
      pathology discussion.

PMID- 9231628
TI  - Takayasu's arteritis: management of a complex case and literature review.
AB  - Takayasu's arteritis, also known as pulseless disease, is an unusual cause of
      symptomatic peripheral vascular disease. It was first reported in 1908 by a
      Japanese ophthalmologist who described retinal arteriovenous shunts which
      appeared in a wreath-like distribution around the optic disc and microaneurysms
      of the retinal vessels in a 19-year-old Japanese woman. Onishi found similar
      findings in association with cool, pulseless upper extremities. Since that time
      the syndrome has been described as Takayasu's arteritis. The current report is of
      a 36-year-old black woman who presented with the complaints of blurred vision,
      dysphagia, headaches, and near syncopal episodes who had been diagnosed with
      Takayasu's arteritis 12 years previously. The presentation and operative
      management is described and this report also reviews the literature on the
      management of this syndrome.

PMID- 9231629
TI  - Meningococcal meningitis.

PMID- 9231630
TI  - Mode of presentation and progress of childhood diabetes mellitus in the Sultanate
      of Oman.
AB  - We surveyed the clinical presentation, initial management and subsequent course
      of a prospectively registered cohort of 60 children with insulin-dependent
      diabetes mellitus (IDDM) diagnosed before age 15 years in the Sultanate of Oman
      between January 1990 and December 1993. Clinical details from the time of
      diagnosis were available on all the children. At diagnosis 9 (15 per cent)
      presented with severe ketoacidosis (DKA) with pH less than 7.1 or plasma
      bicarbonate less than 10 mmol/l, and 16 (27 per cent) had mild to moderate
      ketoacidosis with pH 7.1-7.35 or plasma bicarbonate 10-18 mmol/l. During DKA
      electrolyte disturbances included: hypokalemia (K < 3.5 mmol/l) 25 per cent),
      hyperkalemia (K > 5.5 mmol/l) (18 per cent) and hyponatremia (Na < 130 mmol/l)
      (40 per cent). Serum creatinine concentrations were high in 25 per cent of
      children with DKA. Within the first year of diagnosis, 17 of the 60 children (28
      per cent) experienced symptomatic hypoglycaemia, which in six (10 per cent) led
      to one or more admissions. Re-admission for unstable glycaemic control, excluding
      acute hypoglycaemia occurred at least once in six children (10 per cent) within 1
      year of diagnosis and in 10 (17 per cent) within 2 years. Statural growth
      velocity (GV) and GVSDS (6.9 +/- 0.85 cm/year and 0.75, respectively) were
      significantly higher in the group of children with good glycaemic control (HbA1C
      = 7.9 +/- 0.4 per cent) compared to those children (3.7 +/- 0.44 cm/ year and 
      1.6, respectively) with bad glycaemic control (HbA1C = 12.5 +/- 1.5 per cent).
      Insulin-like growth factor-I (IGF-I) concentrations were significantly higher
      (260 +/- 21 ng/ml) in the group with good glycemic control v. the group with bad
      control (149 +/- 15 ng/ml). In summary, greater public and medical awareness of
      the presenting features of diabetes in young children is needed to reduce the
      frequency of DKA at presentation, and improvement of patient and family education
      is necessary to reduce the incidence of DKA and hypoglycaemia in children with
      IDDM.

PMID- 9231631
TI  - Acute respiratory infections in children: a community-based longitudinal study in
      rural Bangladesh.
AB  - A community-based logitudinal study conducted in Matlab, a rural area in
      Bangladesh, investigated acute respiratory infections (ARI) among children. A
      cohort of 696 children under 5 years of age was followed for 1 year yielding
      183,865 child-days of observation. Trained field workers visited the study
      children every fourth day. Data on symptoms suggesting ARI, such as fever, cough,
      and nasal discharge, were collected for the preceding 3 days by recall. To
      determine the type and severity of ARI, the field workers conducted physical
      examinations (temperature, rate of respiration, and chest indrawing) of children
      reporting cough and/or fever. The overall incidence of ARI was 5.5 episodes per
      child-year observed; the prevalence was 35.4 per hundred days observed. Most of
      the episodes (96 per cent) were upper respiratory infections (URI). The incidence
      of acute lower respiratory infections (ALRI) was 0.23 per child per year. The
      incidence of URI was highest in 18-23-month-old children, followed by infants 6
      11 months old. The highest incidence of ALRI was observed in 0-5-month-old
      infants followed by 12-17-month-old children. Among 559 children who were
      followed for 6 months or longer, about 9 per cent did not suffer any URI episode
      and about 16 per cent suffered one or more ALRI episodes. About 46 per cent of
      URI and 65 per cent of ALRI episodes lasted 15 days or more. The incidence rates
      of URI were higher during the monsoon and pre-winter periods, and that of ALRI at
      the end of the monsoon and during the pre-winter periods. Sociodemographic
      variables were not associated with the incidence of URI or ALRI. The study
      documents ARI to be a major cause of morbidity among rural Bangladeshi children.

PMID- 9231632
TI  - Infantile cholestasis in the Central-Eastern Province Saudi Arabia.
AB  - In the King Khalid University Hospital (Central Province) and King Fahad Hospital
      of the University (Eastern Province) Saudi Arabia, we identified 64 infants with
      cholestasis. The causes of cholestasis were idiopathic neonatal hepatitis in 29;
      extrahepatic biliary atresia in 17; neonatal hepatitis secondary to Rubella and
      Cytomegalovirus in six and four infants, respectively; paucity of intrahepatic
      bile ducts in six and galactosaemia in two. The diagnosis was confirmed by liver
      biopsy and or operative cholangiography, in all infants.

PMID- 9231633
TI  - Profile and outcome of the respiratory distress syndrome among newborns in
      Karachi: risk factors for mortality.
AB  - Although survival data on very low birth weight (VLBW) infants from developing
      countries indicates that mortality rates are high, there is considerable
      disagreement on the relative contribution of respiratory distress syndrome to
      neonatal morbidity and mortality. With improving facilities for newborn care, it
      is now possible to provide basic respiratory support to some babies with RDS in
      selected centres. We prospectively evaluated the profile and outcome of newborn
      infants with respiratory distress admitted to the newborn services at Aga Khan
      University Hospital in Karachi. The overall mortality for newborns with
      documented RDS was 81/200 (41 per cent), and was highest (70 per cent) for babies
      weighing < 1000 g at birth. Univariate and logistic regression analysis of
      factors significantly associated with high risk of dying despite respiratory
      support, included low apgar score at one minute (P = 0.003), admission AaDO2
      value > 400 (P = 0.001), development of acute renal failure (Relative risk 6.2,
      95 per cent confidence interval 1.0-40.0), intraventricular haemorrhage (RR 2.6,
      95 per cent CI 1.3-5.2) and pneumothorax (RR 3.7, 95 per cent CI 1.8-7.7). Our
      data highlight the importance of the immediate postnatal period in infants with
      RDS and suggest that close attention to early stabilization of VLBW infants with
      RDS, may further reduce the mortality associated with this disorder.

PMID- 9231634
TI  - Depletion of glomerular anionic sites and proteineuria in nephrotic syndrome of
      children.
AB  - The number and distribution of glomerular anionic sites using polyethyleneimine
      (PEI) and the ultrastructural changes in the adjacent glomerular basement
      membrane (GBM) of 33 children with nephrotic syndrome were studied. Compared to
      the number of PEI-labelled anionic sites in the lamina rara externa per 1000 nm
      length of the GBM in eight controls (mean +/- SD, 25.0 +/- 1.49); there was a
      significant decrease in four patients with minimal change nephrotic syndrome
      (MCNS; 15.25 +/- 2.98, P < 0.05); 10 patients with focal glomerulosclerosis (16.0
      +/- 5.1, P < 0.014); 14 patients with membranous nephropathy (14.1 +/- 3.83, P <
      0.009), and five patients with membranoproliferative glomerulonephritis (20.04 +/
      1.69, P < 0.036). A moderate inverse correlation between anionic site numbers
      and proteineuria (estimated by urinary protein creatinine ratio) was found in
      MCNS only (r = -0.6). These findings suggest that a reduction in the glomerular
      anionic sites may be only partly responsible for proteineuria in the different
      types of childhood nephrosis, except for minimal change nephrotic syndrome, where
      it probably plays a major role.

PMID- 9231635
TI  - Anaerobes in neonatal septicaemia: a cause for concern.
AB  - The purpose of this study was to determine the prevalence and vertical
      transmission of anaerobic infection in early onset neonatal septicaemia in babies
      born to mothers with adverse perinatal factors. One-hundred neonates born to
      mothers with one or more adverse perinatal factors were prospectively studied.
      Aerobic and anaerobic blood cultures were drawn in addition to rapid diagnostic
      tests. High vaginal swabs were also taken from all mothers prior to delivery.
      Anaerobic Clostridium species infection was found in 5 per cent babies and all of
      them were symptomatic. Fifteen babies had aerobic infection. There was one baby
      with concomitant aerobic and anaerobic infection. There was no significant
      difference in sex distribution, birth weight, or gestational age between babies
      with aerobic and anaerobic infection. Similarly, there were no symptoms unique to
      anaerobic infection. None of the rapid diagnostic tests had a good sensitivity
      for anaerobic infection. Fifty-two per cent of the mothers had anaerobic growth
      in their vaginal swabs, but none had transmitted to their babies. All five babies
      recovered within 24-72 h of commencing therapy. This study shows that anaerobes
      have a role in early onset neonatal septicaemia. They cause serious morbidity,
      but carry a good prognosis. For identification of such infection blood culture is
      mandatory.

PMID- 9231636
TI  - An analysis of prognostic variables in acute lymphocytic leukaemia in a
      heterogenous South African population.
AB  - The records of all 96 children below the age of 15 years diagnosed with acute
      lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South Africa
      between 1983 and 1995 were reviewed to determine risk factors which may predict
      poor outcome. Age < 2 and > 8 years, and white cell count > 20 x 10(9)/l at
      diagnosis were significant predictors of poor outcome. Sex, FAB classification,
      immunophenotype, hepatomegaly, splenomegaly, BFM risk score, and the presence of
      mediastinal glands did not predict outcome. The presence of the established risk
      factors could not adequately explain the difference in 5-year event-free survival
      in the three ethnic groups which was 67 per cent in white, 17 per cent in black,
      and 38 per cent in children of mixed ethnic origin. In an attempt to improve
      survival in black children, our stratification of risk groups will in future be
      based on factors that include ethnicity, age and WCC > or = 20 x 10(9)/l at
      diagnosis. Pediatric oncology services in developing countries should adapt
      therapy to the risk factors of their local populations.

PMID- 9231637
TI  - Human fascioliasis: clinical features and diagnostic difficulties in Egyptian
      children.
AB  - Human fascioliasis (HF) has been reported in children worldwide and occasionally
      from Egypt. In the past 7 years we diagnosed 16 children aged 3.5-11 years (mean
      age: 6.5 years), 13 of them were boys, as HF. They were referred to Cairo
      University, Paediatric Hospital (CUPH), with pyrexia of undetermined origin (PUO)
      and abdominal pain. Diagnosis was based on high peripheral blood eosinophilia (14
      82 per cent) in all patients along with Fasciola hepatica egg detection on direct
      stool smear in three or stool concentration in four, antibody detection by
      indirect haemagglutination test (IHAT) in seven egg-negative patients and
      ultrasonographic detection of hepatic and/or biliary lesions of HF in two egg
      negative patients. Percutaneous liver biopsy confirmed the diagnosis of an
      eosinophilic abscess (parasitic granuloma) in 12 of 13 patients. Therefore, HF
      does occur in Egyptian children and its diagnosis needs a high index of suspicion
      supported by stool microscopy, serology, imaging procedures, and probably liver
      biopsy.

PMID- 9231638
TI  - Cost-effectiveness of surfactant replacement therapy in a developing country.
AB  - A comparison study was conducted to evaluate the cost effectiveness of surfactant
      replacement therapy in the treatment of hyaline membrane disease (HMD). Study
      population included neonates admitted because of HMD severe enough to require
      assisted ventilation with FiO2 greater that 0.4 per cent. This group (n = 44) was
      compared with the outcome for neonates treated in the same centre 1 year before
      surfactant became available (n = 39). Comparison between the two groups was made
      in relation to cost of care depending on the duration of hospitalization. The
      duration of hospitalization in the survivors of the treated group was shorter (P
      = 0.06); accordingly, the cost of care was less. A savings of US $11,880 per
      patient survived in the treated group was expected, the nationwide financial
      impact of this treatment modality is discussed.

PMID- 9231639
TI  - Neonatal resuscitation and newborn outcomes in rural Kenya.
AB  - Neonatal resuscitation methods vary in developing countries. This study describes
      the delivery experience at one rural Kenyan mission hospital, retrospectively
      analysing delivery data and newborn outcomes for a 12-month period, and
      prospectively characterizing neonatal resuscitation practices. Thirty-six of 878
      newborns (4 per cent) suffered unfavourable outcomes, significantly associated
      with caesarean, breech, and vacuum deliveries (nine infants, P < 0.01) and
      birthweight of 2000 g or less (10 infants, P < 0.001). Observed neonatal
      resuscitation practices were inconsistent and notable for umbilical vein
      injections given in lieu of bag and mask ventilation. A basic neonatal
      resuscitation protocol was developed. It is concluded that at one Kenyan
      hospital, unfavourable newborn outcomes were significantly associated with
      delivery other than normal vaginal and with birthweights of 2000 g or less.
      Neonatal resuscitation methods could be modified for use in this setting, and
      might be most useful for term infants delivered by caesarean, breech, or vacuum
      deliveries.

PMID- 9231640
TI  - Intraventricular haemorrhage in premature infants: a study from Oman.
AB  - In a prospective study at Sultan Qaboos University Hospital, 95 premature infants
      with birthweights equal or less than 1500 g were screened for intraventricular
      haemorrhage (IVH) using cranial ultrasound. Nineteen (20 per cent) were found to
      have developed IVH. Eight out of fourteen variables studied showed a significant
      difference between infants who did and those who did not develop IVH. These
      variables were Apgar score at 1 and 5 min, mechanical ventilation (IPPV), blood
      transfusion, receiving boluses of sodium bicarbonate for correction of metabolic
      acidosis, the degree of acidosis, the degree, and duration of hypercarbia (CO2 >
      8 kPa).

PMID- 9231641
TI  - Sexually-transmitted disease (STD) markers in multitransfused children in
      relation to human immunodeficiency virus type-1 (HIV-1) infection: impact of STD
      markers in blood donors.
AB  - Association of serological markers for various sexually transmitted diseases
      (STDs) with Human Immunodeficiency Virus type 1 (HIV-1) infection among
      heterosexually promiscuous blood donors is well recognized. However, possibility
      of similar association among children receiving transfusion from these donors has
      not been adequately explored. Study on the association of some STD markers with
      HIV-1 infection in multitransfused (MT) children showed that both HIV-1 positive
      and HIV-1 negative groups of children had significantly higher prevalence of
      hepatitis B virus (HBV) markers, i.e. HBsAg (23 and 30 per cent), anti-HBs (46
      and 57 per cent), anti-HBc (18 and 23 per cent), antibodies to cytomegalovirus of
      IgM class (36 and 37 per cent) and IgG class (72.7 and 70 per cent), IgG
      antibodies to Herpes Simplex Virus type-2 (23 and 23 per cent) compared to
      control group. However, seropositivity for HIV-1 infection could not be
      attributed as a risk factor for any of these markers in the group of MT children.
      On the contrary, significant association of anti HBc, anti HCV, CMV IgG and
      antitreponemal antibody with HIV-1 infection could be recorded in the group of
      blood donors. It appeared that due to low prevalence of HIV-1 infection among
      blood donors in India, both HIV-1 positive and HIV-1 negative groups of MT
      children received transfusion from HIV negative donors predominantly resulting in
      a comparable prevalence of STD markers in both the groups of MT children due to
      cumulative effect of transfusion from HIV-1 negative donors.

PMID- 9231642
TI  - Transfontanelle ultrasonography in infants: comparative study with cranial
      computed tomography.
AB  - The findings of transfontanelle ultrasonography, undertaken in 36 infants with
      clinical evidence of central nervous system (CNS) disorders, were compared with
      the findings of cranial computed tomography (CT). Considering the CT scan
      findings as gold standard, cranial ultrasonography had a sensitivity of 82 per
      cent and a specificity of 75 per cent in identifying cerebral pathology. The
      positive predictive value was 92 per cent and negative predictive value was 45
      per cent.

PMID- 9231644
TI  - Leprosy: an unusual cause of arthritis in children. A report of two cases.

PMID- 9231643
TI  - Prevalence of beta-thalassaemia trait in 1124 students from Aegean region of
      Turkey.
AB  - Although the beta (beta) thalassaemia carrier frequency in Turkey was stated to
      be 2 per cent, the prevalence rate varies widely in different regions and there
      is limited data confirming the disorder in Aegean region. This prevalence study
      was planned to determine frequency of beta thalassaemia trait in the Aegean
      region among 1124 high school students, between 13 and 18 years old, who were
      selected as target population. Sensitivity of mean corpuscular volume (MCV) and
      mean corpuscular haemoglobin (MCH) in prediction of beta thalassaemia trait were
      evaluated. Venous blood samples were obtained for haemoglobin electrophoresis,
      HbA2 and HbF, serum iron and total iron binding capacity from students in whom
      the levels of haemoglobin (Hb), haemotocrite (Hct), MCV, or MCH, were low
      compared to normal values. The prevalence of beta thalassaemia trait in Aegean
      region was 3 per cent. Sensitivity of MCV and MCH for determining beta
      thalassaemia trait were 100 and 96 per cent, respectively.

PMID- 9231645
TI  - Neutralizing antibodies to poliovirus types 1 and 3 in cord blood of Nigerian
      children.

PMID- 9231646
TI  - Cardioprotective effect of carnitine in fulminant diphtheria.

PMID- 9231647
TI  - Scientific and political impediments to successful islet transplantation.
AB  - Islet transplantation is a treatment for diabetes that has the potential to
      normalize glucose levels and prevent the development of complications. In spite
      of the simplicity of the concept and the urgent need to provide such a treatment
      to patients, there has been a frustrating lack of progress. This perspective
      delves into the scientific and political impediments to success. The scientific
      barriers are the need to find a satisfactory source of insulin-producing tissue
      and the requirement to prevent this tissue from being destroyed by immune
      rejection and autoimmunity. The problems and potential of allografts, xenografts,
      and the development of cell lines are discussed. Multiple approaches to the
      prevention of immune destruction are considered, including immunobarrier devices,
      immunosuppression, development of tolerance, and genetic manipulation. The
      political barriers discussed include the problems of high expectations, the
      controversy surrounding targeted research, the balance between basic and applied
      research, the roles of industry and academia, the concerns about
      xenotransplantation, and the difficulties in developing a planned approach to the
      problem.

PMID- 9231648
TI  - CL-316,243, a beta3-specific adrenoceptor agonist, enhances insulin-stimulated
      glucose disposal in nonobese rats.
AB  - Administration of the murine-selective beta3 adrenoceptor agonist CL-316,243
      corrects obesity and elevated blood glucose in diabetic rodents. This antiobesity
      effect is attributed to an increase in the thermogenic activity of brown adipose
      tissue (BAT). The antidiabetic effect is unknown, but has been attributed to the
      decline in body weight and plasma free fatty acids (FFAs). This study using the
      euglycemic-hyperinsulinemic clamp method was performed in nonobese, nondiabetic
      Sprague-Dawley rats fed normal rodent chow to determine if the beta3 agonist
      could improve insulin sensitivity and/or responsiveness in the absence of weight
      loss or lowering of circulating FFAs. Subcutaneous miniosmotic pumps delivered
      either saline to control or 1 mg x kg(-1) x day(-1) of CL-316,243 for 10-12 days.
      Fed plasma glucose, insulin, and FFA levels were similar between the groups.
      Significant increases in food consumption, resting metabolic rates, and body core
      temperatures occurred, but only after 7 days of treatment. A 14% decrease in the
      respiratory quotient was also observed. Plasma glucose and insulin excursions in
      response to an oral glucose load (2 g/kg) on day 11 were unaltered. Cl-316,243
      treatment resulted in a decrease in abdominal and epididymal white fat pad
      weights, while interscapular brown adipose tissue (IBAT) weight doubled. Basal
      and insulin-stimulated whole-body glucose disposal rates were increased, while
      hepatic glucose output was suppressed to a greater extent in the CL-316,243
      animals after 10 days of uninterrupted treatment. Chronic treatment with CL
      316,243 resulted in an increase in basal and insulin-stimulated [3H]2
      deoxyglucose (2-DG) uptake by the retroperitoneal and epididymal white tissue and
      IBAT, but skeletal muscle 2-DG uptake under the same conditions was unaltered.
      These studies demonstrate that treatment with CL-316,243 improves basal and
      insulin-stimulated glucose disposal, and these effects occurred in the absence of
      a decrease in body weights and FFA concentrations. A particularly interesting
      observation was that the tissues responsible for this effect were white and brown
      adipose tissue, while skeletal muscle remained unaffected.

PMID- 9231649
TI  - Preserved GLP-I effects on glycogen synthase a activity and glucose metabolism in
      isolated hepatocytes and skeletal muscle from diabetic rats.
AB  - To search if biological effects of GLP-I on glucose metabolism in extrapancreatic
      tissue are present in diabetic states, we have studied the action of GLP-I and
      insulin on glycogen-enzyme activity, glycogen synthesis, and glucose metabolism
      in isolated hepatocytes and soleus muscle from adult streptozotocin (STZ)- and
      neonatal STZ-treated diabetic rats. This work confirms the previously reported
      insulin-like effects of GLP-I on glucose metabolism in both muscle and liver
      tissue from normal rats (control). The present study extends those observations
      to the muscle and liver tissue of diabetic animals. In both muscle and liver
      tissue, the metabolism of D-glucose, in the absence of added peptides, was more
      severely affected in adult STZ (IDDM model) than in neonatal STZ (nSTZ; NIDDM
      model) rats, and the magnitude of hormonal effect on metabolic variables was
      lower in diabetic rats than in control rats, as a rule. Nevertheless, in liver
      and muscle tissue of diabetic rats, GLP-I was able to increase glycogen synthase
      activity, augment the net rate of D-[U-14C]glucose incorporation into glycogen,
      and increase D-[5-3H]glucose utilization, D-[U-14C]glucose oxidation, and lactate
      production. In conclusion, GLP-I exerts insulin-like effects on D-glucose
      metabolism in both muscle and liver tissue in IDDM or NIDDM animal models, and
      present observations reinforce the view that GLP-I may represent a most promising
      tool in the treatment of diabetic patients.

PMID- 9231650
TI  - Value of antibodies to islet protein tyrosine phosphatase-like molecule in
      predicting type 1 diabetes.
AB  - Islet antigens associated with type 1 diabetes include a recently identified
      protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular
      fragment IA-2ic. To determine whether combinations of antibodies including those
      to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2,
      IA-2ic, glutamic acid decarboxylase (GAD65), and islet cell antibodies (ICAs) in
      1) 60 newly diagnosed type 1 diabetic patients followed for 1 year, 2) 31
      monozygotic twin pairs discordant for type 1 diabetes followed up to 12 years (11
      twins developed diabetes), 3) 18 dizygotic twin pairs discordant for type 1
      diabetes, and 4) normal healthy control subjects. Newly diagnosed type 1 diabetic
      patients frequently had antibodies to IA-2 (62%), IA-2ic (67%), GAD65 (77%), and
      ICAs (85%). The intracellular fragment of IA-2 probably contains the
      immunodominant epitope as 137 of 143 samples with IA-2 antibodies from type 1
      diabetic patients also had IA-2ic antibodies. Monozygotic twins were usually
      discordant for antibody specificities. Concordance was higher in monozygotic than
      matched dizygotic twins for both antibody combinations (33 vs. 6%, P < 0.05) and
      the development of diabetes (33 vs. 0%, P < 0.01). In monozygotic twins, all the
      antibodies were highly predictive of type 1 diabetes (positive predictive values
      all >87%), although antibodies were also detected in twins at low risk of
      disease. In summary, IA-2 emerges as a major antigen associated with type 1
      diabetes and distinct from GAD65. Type 1 diabetes-associated autoimmunity, which
      is probably induced by environmental factors, does not necessarily herald
      progression to the disease. However, genetic factors may influence the
      development of combinations of disease-associated antibodies and the progression
      to type 1 diabetes.

PMID- 9231651
TI  - beta-cell function in normal rats made chronically hyperleptinemic by adenovirus
      leptin gene therapy.
AB  - Leptin was overexpressed in the liver of normal Wistar rats by infusing
      recombinant adenovirus containing the cDNA encoding leptin. Plasma leptin levels
      rose to 12-24 ng/ml (vs. <2 ng/ml in control rats), and food intake and body
      weight fell. Visible fat disappeared within 7 days. Plasma insulin fell to <50%
      of normal in association with hypoglycemia, suggesting enhanced insulin
      sensitivity. Although beta-cells appeared histologically normal, the pancreases
      were unresponsive to perfusion with stimulatory levels of glucose and arginine.
      Since islet triglyceride content was 0, compared with 14 ng/islet in pair-fed
      control rats, we coperfused a 2:1 oleate:palmitate mixture (0.5 mmol/l). This
      restored insulin responses to supranormal levels. When normal islets were
      cultured with 20 ng/ml of leptin, they too became triglyceride-depleted and
      failed to respond when perifused with glucose or arginine. Perifusion of fatty
      acids restored both responses. We conclude that in normal rats, hyperleptinemia
      for 2 weeks causes reversible beta-cell dysfunction by depleting tissue lipids,
      thereby depriving beta-cells of a lipid-derived signal required for the insulin
      response to other fuels.

PMID- 9231653
TI  - Mitochondrial DNA in beta-cells is a sensitive target for damage by nitric oxide.
AB  - Increasing evidence indicates that nitric oxide (NO) may play a role in immune
      mediated injury to beta-cells. One site for the action of this agent is the
      mitochondrion. Although the exact targets for damage within this organelle have
      yet to be fully elucidated, a potential location for injury is mitochondrial DNA
      (mtDNA). Therefore, experiments were initiated to evaluate damage to mtDNA caused
      by NO. Both exogenous NO generation (spermine/NO adduct [sper/NO]) and endogenous
      production of NO (IL-1beta) were studied. To study the effects of exogenously
      produced NO, neonatal rat islet cells in monolayers were exposed to varying doses
      of sper/NO for 30 min. Total cellular DNA was isolated and treated with alkali to
      produce strand breaks at abasic sites resulting from exposure to NO. Damage to
      mtDNA was evaluated using a quantitative Southern blot technique. The results
      showed that sper/NO caused dose-dependent damage to mtDNA. Additionally, mtDNA
      was found to be more sensitive to injury generated by either source than a
      similarly sized fragment of nuclear DNA. To evaluate the effects of endogenously
      produced NO, beta-cell cultures were treated with IL-1beta for 18 h. Other
      cultures were treated with IL-1beta and an inhibitor of the inducible form of
      nitric oxide synthase, aminoguanidine. DNA was evaluated as described for the
      sper/NO studies. IL-1beta caused appreciable damage to mtDNA, and this damage was
      reduced in mtDNA from cultures treated with IL-1beta and aminoguanidine. These
      studies show that mtDNA is a sensitive target for NO generated both endogenously
      and exogenously and that this DNA is more vulnerable to NO-induced damage than
      nuclear DNA.

PMID- 9231652
TI  - Demonstration of two different processes of beta-cell regeneration in a new
      diabetic mouse model induced by selective perfusion of alloxan.
AB  - To clarify the regeneration process of pancreatic beta-cells, we established a
      new mouse model of diabetes induced by selective perfusion of alloxan after
      clamping the superior mesenteric artery. In this model, diabetes could be induced
      by the destruction of beta-cells in alloxan-perfused segments, while beta-cells
      in nonperfused segments were spared. Intraperitoneal glucose tolerance tests
      showed glucose intolerance, which gradually ameliorated and was completely
      normalized in 1 year with a concomitant increase of insulin content in the
      pancreas. Histological examination showed neo-islet formation in the alloxan
      perfused segment and the proliferation of spared beta-cells in the nonperfused
      segment. In the alloxan-perfused segment, despite a marked reduction of islets in
      size and number at an early stage, both the number of islets, including islet
      like cell clusters (ICCs), and the relative islet area significantly increased at
      a later stage. Increased single beta-cells and ICCs were located in close contact
      with duct cell lining, suggesting that they differentiated from duct cells and
      that such extra-islet precursor cells may be important for beta-cell regeneration
      in beta-cell-depleted segment. In addition to beta-cells, some nonhormone cells
      in ICCs were positive for nuclear insulin promoter factor 1, which indicated that
      most, if not all, nonhormone cells positive for this factor were beta-cell
      precursors. In the nonperfused segment, the islet area increased significantly,
      and the highest 5-bromo-2-deoxyuridine-labeling index in beta-cells was observed
      at day 5, while the number of islets did not increase significantly. This
      indicated that the regeneration of islet endocrine cells occurs mostly through
      the proliferation of preexisting intra-islet beta-cells in the nonperfused
      segment. In conclusion, the regeneration process of beta-cells varied by
      circumstance. Our mouse model is useful for studying the mechanism of
      regeneration, since differentiation and proliferation could be analyzed
      separately in one pancreas.

PMID- 9231654
TI  - Proprotein-processing endoprotease furin controls growth of pancreatic beta
      cells.
AB  - We have previously reported that in the well-differentiated beta-cell line MIN6
      cells, the beta-cell-specific differentiated characteristics, such as insulin
      content, expression of prohormone convertases PC2 and PC3, and glucose-regulated
      insulin secretion, diminished when the proprotein-processing endoprotease furin
      was highly expressed. Since furin converts many growth-related protein precursors
      to their bioactive forms, we compared the four pancreatic islet cell lines
      RINm5F, betaTC3, betaHC9, and MIN6 with respect to cell growth rate, furin
      expression, endoprotease activity, and insulin content. RINm5F cells exhibited
      the strongest furin expression, higher furin-type endoprotease activity, and the
      fastest cell growth, but had the least insulin content. In contrast, MIN6 cells
      exhibited only a weak furin expression, little furin-type endoprotease activity,
      and the slowest cell growth, but had the highest insulin content. To test whether
      furin-expressing cells secrete growth-promoting factors cleaved by furin, we
      prepared conditioned media from RINm5F and furin cDNA-introduced MIN6 (MIN6-F)
      cells. The conditioned media from RINm5F and MIN6-F induced increased DNA
      synthesis and promoted the growth of normal MIN6 cells, compared with the medium
      from the empty vector-introduced MIN6-0 cells. We then examined the effect of the
      protease inhibitors alpha1-antitrypsin and its variants by infecting their
      vaccinia recombinants to the four cell lines. All conditioned media from each
      cell line expressing the furin-specific alpha1-antitrypsin variant exhibited the
      least DNA synthetic capacity on normal MIN6 cells. Furthermore, all three
      sublines of MIN6-F grew faster than MIN6-0 and MIN6. Thus, we suggest that the
      islet cells with higher furin expression may induce increased production of
      growth factors, which result in an increase in cell growth, through an
      autocrine/paracrine mechanism.

PMID- 9231655
TI  - Energetic requirement of insulin secretion distal to calcium influx.
AB  - A number of agents that inhibit oxidative phosphorylation by different mechanisms
      (carbonyl cyanide mchlorophenylhydrazone [CCCP], sodium azide, oligomycin)
      induced an increase of cytoplasmic Ca2+ concentration ([Ca2+]i) in pancreatic
      beta-cells, as measured by microfluorimetry with digital imaging. All three
      agents are known inhibitors of insulin secretion, and the secretory response to
      20 mmol/l glucose was found to be abolished in spite of elevated [Ca2+]i. Two
      reasons could account for this dissociation between increase of [Ca2+]i and
      insulin secretion: 1) the increase did not take place at a site critical for
      exocytosis, 2) a threshold concentration of a metabolism-derived factor like ATP
      exists for the induction of exocytosis. The increase of [Ca2+]i by CCCP and
      sodium azide involved release of Ca2+ from internal stores, whereas oligomycin
      induced a slow D 600-inhibitable Ca2+ influx. Because CCCP and sodium azide, but
      not oligomycin, decreased the mitochondrial membrane potential concomitantly with
      the increase of [Ca2+]i, release of Ca2+ from the mitochondria most probably
      plays a decisive role for the internal mobilization. A Ca2+ influx induced by 40
      mmol/l K+ or 250 micromol/l tolbutamide was unimpaired in the presence of
      oligomycin, but oligomycin completely abolished insulin secretion in response to
      these agents. While CCCP and sodium azide opened ATP-sensitive K+ channels,
      oligomycin was virtually ineffective, although it could be shown to significantly
      reduce beta-cell ATP production. By comparison of the effects of different
      inhibitors of oxidative phosphorylation, we conclude that the initiation of
      exocytosis in beta-cells is particularly sensitive to a decrease of energy
      metabolism, more than ATP-sensitive K+ channels or voltage-dependent Ca2+
      channels. Thus, any increase of [Ca2+]i in beta-cells that occurs in a situation
      of a decreased ATP supply is unlikely to elicit a secretory response.

PMID- 9231656
TI  - Atrial natriuretic peptide and cyclic nucleotides affect glucose-induced Ca2+
      responses in single pancreatic islet beta-cells: correlation with (Ca[2+] + Mg2+)
      ATPase activity.
AB  - Glucose stimulation of pancreatic islets is characterized by an initial decline
      in intracellular Ca2+ concentration ([Ca2+]i) (phase 0), followed by an increase
      in peak [Ca2+]i (phase 1). The effect of atrial natriuretic peptide (ANP) and
      cyclic nucleotides on the glucose-induced phase 0 [Ca2+]i was investigated by
      Fura-2 fluorescent imaging in single beta-cells from isolated islets of rats
      maintained at 1.67 mmol/l glucose. ANP (1 nmol/l to 1 micromol/l) inhibited the
      glucose (8.2 mmol/l)-induced phase 0 [Ca2+], in a concentration-dependent manner.
      Forskolin, 8-bromo-cyclic AMP (8BrcAMP), and 8-bromo-cyclic guanosine
      monophosphate (8BrcGMP) also inhibited the glucose-induced phase 0 [Ca2+]i. The
      Ca2+ channel blocker, D 600, prevented the response to 8BrcAMP but not to ANP or
      8BrcGMP on phase 0 [Ca2+]i. Thapsigargin (TG) also inhibited phase 0 [Ca2+]i by
      90%. ANP, 8BrcGMP, and TG also reduced the time required for glucose to initiate
      the phase 1 increase in [Ca2+]i, and each of these agents potentiated the effect
      of glucose on peak [Ca2+]i. Furthermore, sarco(endo)-plasmic reticulum (Ca[2+] +
      Mg2+)-ATPase (SERCA) activity in RINm5F insulinoma cells was inhibited by 8BrcGMP
      and TG, but not 8BrcAMP. Thus, ANP and cGMP modulate [Ca2+]i regulation in
      pancreatic beta-cells perhaps through mechanisms involving changes in SERCA
      activity and Ca2+ influx.

PMID- 9231657
TI  - Tissue distribution and quantification of the expression of mRNAs of peroxisome
      proliferator-activated receptors and liver X receptor-alpha in humans: no
      alteration in adipose tissue of obese and NIDDM patients.
AB  - Members of the peroxisome proliferator-activated receptor (PPAR) family might be
      involved in pathologies with altered lipid metabolism. They participate in the
      control of the expression of genes involved in lipid metabolism and adipocyte
      differentiation. In addition, thiazolidinediones improve insulin resistance in
      vivo by activating PPAR gamma. However, little is known regarding their tissue
      distribution and relative expression in humans. Using a quantitative and
      sensitive reverse transcription (RT)-competitive polymerase chain reaction (PCR)
      assay, we determined the distribution and relative mRNA expression of the four
      PPARs (alpha,beta, gamma1, and gamma2) and liver X receptor-alpha (LXR alpha) in
      the main tissues implicated in lipid metabolism. PPAR alpha and LXR alpha were
      mainly expressed in liver, while PPAR gamma1 predominated in adipose tissue and
      large intestine. We found that PPAR gamma2 mRNA was a minor isoform, even in
      adipose tissue, thus causing question of its role in humans. PPAR beta mRNA was
      present in all the tissues tested at low levels. In addition, PPAR gamma mRNA was
      barely detectable in skeletal muscle, suggesting that improvement of insulin
      resistance with thiazolidinediones may not result from a direct effect of these
      agents on PPAR gamma in muscle. Obesity and NIDDM were not associated with change
      in PPARs and LXR alpha expression in adipose tissue. The mRNA levels of PPAR
      gamma1, the predominant form in adipocytes, did not correlate with BMI, leptin
      mRNA levels, or fasting insulinemia in 29 subjects with various degrees of
      obesity. These results indicated that obesity is not associated with alteration
      in PPAR gene expression in abdominal subcutaneous adipose tissue in humans.

PMID- 9231658
TI  - Effects of differing antecedent hypoglycemia on subsequent counterregulation in
      normal humans.
AB  - The aim of the study was to determine the effects of specific levels of
      antecedent hypoglycemia on subsequent autonomic, neuroendocrine, and metabolic
      counterregulatory responses. Eight healthy, overnight-fasted male subjects were
      studied during 2-day protocols on four separate randomized occasions separated by
      at least 2 months. On day 1, insulin was infused at a rate of 9 pmol x kg(-1) x
      min(-1) and 2-h clamped euglycemia (plasma glucose 5.2 +/- 0.2 mmol/l) or
      differing hypoglycemia (plasma glucose 3.9 +/- 0.1, 3.3 +/- 0.1, or 2.9 +/- 0.1
      mmol/l) was obtained during morning and afternoon. The next morning after an
      evening meal and 10-h overnight fast, each subject underwent a 2-h
      hyperinsulinemic (9 pmol x kg(-1) x min[-1]) hypoglycemic (2.9 +/- 0.1 mmol/l)
      clamp study. Despite equivalent day 2 plasma glucose and insulin levels,
      differing levels of antecedent hypoglycemia produced specific blunting of
      subsequent counterregulatory responses. Day 1 hypoglycemia of 3.9 mmol/l resulted
      in significantly (P < 0.01) blunted epinephrine, muscle sympathetic nerve
      activity, and glucagon responses. Day 1 hypoglycemia of 3.3 mmol/l resulted in
      additional significant blunting (P < 0.01) of pancreatic polypeptide,
      norepinephrine, growth hormone, endogenous glucose production, and lipolytic
      responses. Deeper day 1 hypoglycemia of 2.9 mmol/l produced similar day 2
      counterregulatory failure as day 1 hypoglycemia of 3.3 mmol/l. In summary, in
      healthy overnight-fasted men, mild antecedent hypoglycemia of 3.9 mmol/l
      significantly blunts sympathoadrenal and glucagon, but not other forms of
      neuroendocrine counterregulatory responses, to subsequent hypoglycemia.
      Antecedent hypoglycemia of 3.3 mmol/l resulted in additional significant blunting
      of all major neuroendocrine and metabolic responses to subsequent hypoglycemia.
      We conclude that in normal humans, there is a hierarchy of blunted
      counterregulatory responses that are determined by the depth of antecedent
      hypoglycemia.

PMID- 9231659
TI  - Skeletal muscle myosin heavy chain synthesis in type 1 diabetes.
AB  - Although insulin's anticatabolic effect on protein metabolism in type 1 diabetes
      has been clearly shown to be related to the inhibition of protein breakdown,
      insulin's effect on muscle protein synthesis remains controversial. Cross-limb
      studies and measurements of synthesis rates of mixed muscle protein have yielded
      conflicting results. These measurements represent the mean synthesis of several
      muscle proteins and may miss changes in the synthesis rates of individual muscle
      proteins. We measured the fractional synthesis rates of myosin heavy chain (MHC),
      the principal muscle contractile protein, and mixed muscle protein (MMP) in six
      type 1 diabetic patients during insulin deprivation and insulin treatment.
      Comparisons were made with six healthy control subjects. Muscle biopsies were
      taken at 2 h and 8 h during a primed continuous infusion of L-[1-13C]leucine. MHC
      was purified by a preparative continuous elution gel electrophoresis, and
      fractional synthesis rates were calculated. We found that in type 1 diabetic
      subjects, the fractional synthesis rates of MHC and MMP during insulin treatment
      are similar to those of control subjects. Acute insulin deprivation did not
      affect either the synthesis rate or the ratio of MHC to MMP in type 1 diabetic
      subjects. In the postabsorptive state, acute insulin deprivation has no effect on
      MHC or MMP synthesis in type 1 diabetic patients.

PMID- 9231660
TI  - Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity
      in Pima Indian children.
AB  - Hyperinsulinemia is commonly associated with obesity, but it has not been
      determined which defect comes first. Some have proposed that hyperinsulinemia may
      precede obesity in populations prone to NIDDM, such as Pima Indians or Pacific
      Islanders. In contrast, longitudinal studies in adults show that insulin
      sensitivity and low fasting insulin concentrations are associated with increased
      weight gain, whereas insulin resistance seems to protect against weight gain. The
      present study examined whether fasting plasma hyperinsulinemia is a risk factor
      for weight gain in prepubertal children in the Pima Indian population-a
      population that is prone to obesity. Fasting plasma insulin concentration was
      measured in 328 5- to 9-year-old Pima Indian children (147 boys and 181 girls)
      with normal glucose tolerance. Follow-up weight was obtained an average of 9.3 +/
      1.9 years (means +/- SD) later at age 15-19 years. Fasting plasma insulin
      concentration correlated with the rate of weight gain per year in both boys (r =
      0.42; P < 0.0001) and girls (r = 0.20; P < 0.01) and was associated with the rate
      of weight gain, independent of known determinants of weight change, i.e., initial
      relative weight, change in height, age, and sex. Similar relationships were found
      between fasting plasma insulin concentration and the change in relative weight
      and in triceps skinfold thickness-two indicators of obesity. In conclusion,
      fasting hyperinsulinemia may be a risk factor for the development of obesity in
      young children.

PMID- 9231661
TI  - Differential effects of streptozotocin-induced diabetes on cardiac lipoprotein
      lipase activity.
AB  - Lipoprotein lipase (LPL) is an endothelial-bound enzyme that is rate determining
      for the clearance of triacylglycerol-rich lipoproteins. Previous studies using
      rats with streptozotocin (STZ)-induced diabetes have reported inconsistent
      effects on cardiac LPL activity or immunoreactive protein. To examine the
      contribution of the severity and duration of diabetes on cellular and heparin
      releasable cardiac LPL activity, Wistar rats were administered a high (100 mg/kg;
      D100) or moderate (55 mg/kg; D55) dose of STZ, and LPL activity was examined at
      various times after diabetes induction. Heparin perfusion of the isolated
      Langendorff control heart induced the release of LPL activity as an initial fast
      phase followed by a slow phase of release. With increasing age, the second phase
      of LPL release became more pronounced. Severe STZ-induced diabetes reduced
      heparin-releasable LPL activity by 1 week in the D100 rats. However, in D55 rat
      hearts, peak heparin-releasable LPL activity was higher than that in control
      animals at 2 and 12 weeks after STZ injection, with a complete absence of the
      delayed phase at 12 weeks. The elevated heparin-releasable LPL peak could not be
      explained by an enhanced LPL synthesis because both cellular and surface-bound
      LPL activities in myocytes from D55 rats were low, relative to control. Chronic
      (12-day) insulin treatment of D55 rats prevented the rise in heparin-releasable
      LDL and the reduction in cell-associated LPL activity. Moreover, acute (90-min)
      treatment of D55 rats with rapid-acting insulin also reduced the heparin
      releasable LPL activity to normal levels, although it had no effect on the low
      cellular LPL activity. When the heparin-releasable LPL pool was allowed to
      recover for 1 h after removal of the enzyme, D55 rat hearts continued to
      demonstrate a higher peak LPL activity after a second heparin perfusion. These
      studies demonstrate that in moderate but not severe diabetes, there is an
      augmented peak heparin-releasable LPL activity. Whether or not this enhanced
      heparin-releasable LPL activity has a pathological role in the diabetic heart has
      yet to be determined.

PMID- 9231662
TI  - Dyslipidemia and hyperglycemia predict coronary heart disease events in middle
      aged patients with NIDDM.
AB  - Patients with NIDDM are at increased risk for coronary heart disease (CHD).
      However, information on the predictive value of cardiovascular risk factors and
      the degree of hyperglycemia with respect to the risk for CHD in diabetic patients
      is still limited. Therefore, we carried out a prospective study on risk factors
      for CHD, including a large number of NIDDM patients. At baseline, risk factor
      levels of CHD were determined in 1,059 NIDDM patients (581 men and 478 women),
      aged from 45 to 64 years. These patients were followed up to 7 years with respect
      to CHD events. Altogether, 158 NIDDM patients (97 men [16.7%] and 61 women
      [12.8%]) died of CHD and 256 NIDDM patients (156 men [26.8%] and 100 women
      [20.9%]) had a serious CHD event (death from CHD or nonfatal myocardial
      infarction). A previous history of myocardial infarction, low HDL cholesterol
      level (<1.0 mmol/l), high non-HDL cholesterol (> or =5.2 mmol/l), high total
      triglyceride level (>2.3 mmol/l), and high fasting plasma glucose (>13.4 mmol/l)
      were associated with a twofold increase in the risk of CHD mortality or
      morbidity, independently of other cardiovascular risk factors. High calculated
      LDL cholesterol level (> or =4.1 mmol/l) was significantly associated with all
      CHD events. The simultaneous presence of high fasting glucose (>13.4 mmol/l) with
      low HDL cholesterol, low HDL-to-total cholesterol ratio, or high total
      triglycerides further increased the risk for CHD events up to threefold. Our 7
      year follow-up study provides evidence that dyslipidemia and poor glycemic
      control predict CHD mortality and morbidity in patients with NIDDM.

PMID- 9231663
TI  - Leptin directly alters lipid partitioning in skeletal muscle.
AB  - Leptin, an adipocyte-derived hormone that directly regulates both adiposity and
      energy homeostasis, decreases food intake and appears to partition metabolic
      fuels toward utilization and away from storage. Because skeletal muscle expresses
      the leptin receptor and plays a major role in determining energy metabolism, we
      studied leptin's effects on glucose and fatty acid (FA) metabolism in isolated
      mouse soleus and extensor digitorum longus (EDL) muscles. One muscle from each
      animal served as a basal control. The contralateral muscle was treated with
      insulin (10 mU/ml), leptin (0.01-10 microg/ml), or insulin plus leptin, and
      incorporation of [14C]glucose or [14C]oleate into CO2 and into either glycogen or
      triacylglycerol (TAG) was determined. Leptin increased soleus muscle FA oxidation
      by 42% (P < 0.001) and decreased incorporation of FA into TAG by 35% (P < 0.01)
      in a dose-dependent manner. In contrast, insulin decreased soleus muscle FA
      oxidation by 40% (P < 0.001) and increased incorporation into TAG by 70% (P <
      0.001). When both hormones were present, leptin attenuated both the antioxidative
      and the lipogenic effects of insulin by 50%. Less pronounced hormone effects were
      observed in EDL muscle. Leptin did not alter insulin-stimulated muscle glucose
      metabolism. These data demonstrate that leptin has direct and acute effects on
      skeletal muscle.

PMID- 9231664
TI  - Pancreatic islet expression studies and polymorphic DNA markers in the genes
      encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6.
AB  - The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha
      and HNF-4alpha play a critical role in normal pancreatic beta-cell function.
      Mutations in these liver-enriched transcription factors result in two forms of
      early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3
      and MODY1, which are characterized by impaired glucose-stimulated insulin
      secretion, early disease onset, and autosomal dominant inheritance. The
      transcriptional hierarchy of HNFs suggests that other proteins of the regulatory
      cascade might be responsible for other forms of MODY and/or late-onset type 2
      diabetes. In this study, we show that HNF-3alpha, -3beta, -3gamma, -4gamma, and 
      6 are expressed in pancreatic beta-cells. We report the identification and
      characterization of simple tandem repeat DNA polymorphisms in the genes encoding
      HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to
      chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. These
      markers will be useful to study the role of genetic variation in these genes in
      the pathogenesis of type 2 diabetes.

PMID- 9231665
TI  - Evidence for acute stimulation of fibrinogen production by glucagon in humans.
AB  - Fibrinogen, an acute-phase protein, and glucagon, a stress hormone, are often
      elevated in many conditions of physical and metabolic stress, including
      uncontrolled diabetes. However, the possible mechanisms for this association are
      poorly known. We have studied the acute effects of selective hyperglucagonemia
      (raised from -200 to -350 pg/ml for 3 h) on fibrinogen fractional secretion rate
      (FSR) in eight normal subjects during infusion of somatostatin and replacement
      doses of insulin, glucagon, and growth hormone. Fibrinogen FSR was evaluated by
      precursor-product relationships using either Phe (n = 8) or Leu (n = 2) tracers.
      Hyperglucagonemia did not change either plasma Phe or Tyr specific activity.
      After hyperglucagonemia, fibrinogen FSR increased by approximately 65% (from 12.9
      +/- 3.6 to 21.5 +/- 6.1% per day, P < 0.025) using plasma Phe specific activity
      as the precursor pool. FSR increased by approximately 80% (from 16.6 +/- 4.8 to
      29.4 +/- 8.8% per day, P < 0.025) if plasma Phe specific activity was corrected
      for the ketoisocaproate/Leu enrichment (or specific activity) ratio to obtain an
      approximate estimate of intrahepatic Phe specific activity. FSR increased by
      approximately 60% when using plasma Tyr specific activity as precursor pool (n =
      8) (P < 0.05), as well as when using the Leu tracer precursor-product
      relationship (n = 2). In conclusion, selective hyperglucagonemia for
      approximately 3 h acutely stimulated fibrinogen FSR using a Phe tracer method.
      Thus, glucagon may be involved in the increase of fibrinogen concentration and
      FSR observed under stressed or pathologic conditions.

PMID- 9231666
TI  - Physician/patient-driven risk assignment in radiation oncology: reality or fancy?
AB  - PURPOSE: Treatment plan optimization in radiation oncology entails designing
      multiple x-ray beams to irradiate a tumor to a dose that will achieve
      locoregional control while minimizing normal tissue complications. For some
      anatomical sites, it is possible to estimate tumor control probabilities (TCP)
      and normal tissue complication probabilities (NTCP) as a function of radiation
      dose. Thus, treatment plan optimization can be based on biologic end points
      rather than on dose calculations alone. Given multiple plans with different NTCPs
      and TCPs, a tradeoff must be made between maximizing TCP and maintaining an
      acceptable NTCP. How do physicians reach these decisions? Can the process be
      quantified? Should patients participate in the process? METHODS AND MATERIALS:
      Physicians and patients were asked to rank a series of treatment plans having
      different combinations of TCP and NTCP. Responses were parametrized into a figure
      of merit (FM) equation which quantifies predilections of TCP and NTCP. RESULTS:
      Physician-based FM equations are site- and patient-specific. Variations exist
      among physicians, but treatment plan selection is often conservative in
      accordance with the primum non nocere dictum. FM equations generated from the
      responses of patients suggest that some patients may be willing to accept higher
      treatment toxicity in exchange for increased TCP. CONCLUSION: The term "optimized
      treatment plan" contains inherently subjective criteria which reflect one's
      willingness to accept treatment morbidity in exchange for probability of cure.
      These criteria may differ among patients and/or physicians. A quantifiable FM may
      permit the design of custom-made treatment plans that include physician and
      patient input.

PMID- 9231667
TI  - High PCNA index in meningiomas resistant to radiation therapy.
AB  - PURPOSE: Meningiomas are common intracranial tumors, often well controlled with
      surgical resection alone. While the efficacy of radiation therapy in improving
      local control and progression-free survival is well documented, prognostic data
      substantiate factors that are predictive of poor local control following
      definitive radiation therapy. PCNA is a DNA polymerase expressed at the highest
      levels in the S-phase, the most resistant portion of the cell cycle to ionizing
      radiation in vitro. We investigated the possible correlation between the levels
      of PCNA expression and the clinical outcome of patients treated with definitive
      radiation therapy. METHODS AND MATERIALS: Archival tissue was collected from 33
      cases of meningioma treated at our institution for definitive radiation therapy
      between 1970 and 1990. Age-matched normal meningeal tissue and asymptomatic
      meningiomas removed at autopsy served as tissue controls. A standard ABC
      immumoperoxidase technique employing antibodies to PCNA, PC-10 (Dako, California)
      was used to stain specimen slides for PCNA. PCNA index was defined as the number
      of positive nuclei per 10 high-power fields at 400x magnification. Two
      independent observers scored the slides without prior knowledge of the cases at
      hand. RESULTS: Patients with high PCNA index were less likely to be controlled by
      therapeutic radiation (p < 0.001, Kaplan-Meier). All patients with a PCNA index
      greater that 25 failed radiation therapy. Using multivariate analyses, malignant
      (but not atypical), histology and PCNA index were significant predictors of
      progression following radiation therapy (p < 0.05, log rank). CONCLUSION: PCNA
      index may be a useful adjunct to more standard histopathologic criteria in the
      determination of meningioma local control and progression-free survival following
      therapeutic irradiation. Data on a more expanded population evaluated on a
      prospective basis will be needed before such criteria are routinely employed in
      the clinical setting.

PMID- 9231668
TI  - The effect of M-stage on patterns of failure in posterior fossa primitive
      neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk
      patient population.
AB  - PURPOSE: To analyze patterns of failure in patients (pts) with high-risk
      posterior fossa primitive neuroectodermal tumors (PF-PNETs) treated with combined
      modality therapy on a large, randomized multiinstitutional study. METHODS AND
      MATERIALS: One hundred eighty-eight prospectively staged pts with PF-PNET
      confirmed by central pathology review, with high-risk features, were treated on
      Children's Cancer Group Study 921 (CCG-921), comparing two chemoradiotherapy
      regimens. Patterns of initial sites of failure were analyzed, specifically
      evaluating the impact of Chang M-stage. RESULTS: Progression-free survival (PFS)
      correlated with the presence or absence of metastatic disease (p < 0.001), with 5
      year PFS of 68 +/- 5.8% for M0 vs. 43 +/- 6.8% for M+ pts. The cumulative
      incidence functions (CIF) of recurrence were different (p = 0.005) and at 5 years
      were 29 +/- 4.7% for M0 pts and 48 +/- 5.5% for M+ pts. Involvement of the PF at
      time of initial failure as measured by CIF correlated with M-stage (p = 0.047)
      and occurred in 18 +/- 3.9% of M0 pts and 8 +/- 2.9% of M+ pts overall; PF as the
      only site of relapse also correlated with M-stage (p = 0.019) and was seen in 6
      +/- 2.5 and 0% of M0 and M+ pts, respectively, at 5 years. Relapse in the spine
      and/or cerebrospinal fluid (CSF) at initial recurrence was correlated with M
      stage (p < 0.002), with 5-year cumulative incidences of 14 +/- 3.7%, 26 +/- 8.2%,
      40 +/- 15%, and 40 +/- 7.7% for M0, M1, M2, and M3 pts, respectively. Isolated
      spine/CSF recurrence correlated with M-stage (p = 0.034) and occurred in 2 +/-
      1.5% of M0 and 9 +/- 3.2% of M+ pts by 5 years. The median time to relapse for
      pts who failed was 1.2 years (range 0.2-5.3). Ninety percent of all relapses
      occurred by 3 years. CONCLUSIONS: Original sites of disease are at the highest
      risk for relapse, but the entire neuraxis remains at significant risk, despite
      combined-modality treatment. M-Stage was prognostic for spine/CSF relapse as well
      as PFS and may be an important tool in guiding therapy. A more aggressive
      approach to local control in the neuraxis is warranted, especially in M+
      patients.

PMID- 9231669
TI  - Potential role of proton therapy in the treatment of pediatric
      medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial
      target volume.
AB  - PURPOSE: One of the components of radiotherapy (RT) in medulloblastoma/primitive
      neuroectodermal tumors is the prophylactic irradiation of the whole brain (WBI).
      With the aim of reducing late neuropsychologic morbidity a CT-scan-based
      dosimetric study was undertaken in which treatment was confined mainly or
      exclusively to supratentorial sites considered at high risk for disease
      recurrence. METHODS AND MATERIALS: A comparative dosimetric study is presented in
      which a three field (two laterals and one posterior) proton plan (spot scanning
      method) is compared with a two-field conventional WBI 6 MV x-ray plan, to a 6
      field "hand-made" 6 MV x-ray plan, and to a computer-optimized 9-field "inverse"
      15 MV x-ray plan. For favorable patients, 30 Gy were delivered to the ventricles
      and main cisterns, the subfrontal and subtemporal regions, and the posterior
      fossa. For the unfavorable patients, 10 Gy WBI preceeded a boost to 30 Gy to the
      same treatment volume chosen for favorable patients. The dose distribution was
      evaluated with dose-volume histograms to examine the coverage of the targets as
      well as the dose to the nontarget brain and optical structures. In addition, the
      risks of radiation-related late neuropsychologic effects after WBI were collected
      from the literature and used to predict normal tissue complication probabilities
      (NTCPs) for an intelligence quotient deficit after treatment with photon or
      proton beams. RESULTS: Proton beams succeeded better in reducing the dose to the
      brain hemispheres and eye than any of the photon plans. A 25.1% risk of an IQ
      score <90 was predicted after 30 Gy WBI. Almost a 10% drop in the predicted risk
      was observed when using proton beams in both favorable and unfavorable patients.
      However, predicted NTCPs for both optimized photon plans ("hand made" and
      "inverse") were only slightly higher (0.3-2.5%) than those of proton beams. An
      age-modifying factor was introduced in the predictive NTCP model to assess for IQ
      differences in relation with age at irradiation. Children with ages between age 4
      to 8 benefitted most from the dose reduction in this exercise (similar NTCP
      predictions for both proton and "inverse" plans). CONCLUSION: Modulated proton
      beams may help to significantly reduce the irradiation of normal brain while
      optimally treating the supratentorial subsites at higher risk for relapse. A
      decrease in morbidity can be expected from protons and both optimized proton
      plans compared to WBI.

PMID- 9231670
TI  - Complications from arteriovenous malformation radiosurgery: multivariate analysis
      and risk modeling.
AB  - PURPOSE/OBJECTIVE: To assess the relationships of radiosurgery treatment
      parameters to the development of complications from radiosurgery for
      arteriovenous malformations (AVM). METHODS AND MATERIALS: We evaluated follow-up
      imaging and clinical data in 307 AVM patients who received gamma knife
      radiosurgery at the University of Pittsburgh between 1987 and 1993. All patients
      had regular clinical or imaging follow up for a minimum of 2 years (range: 24-96
      months, median = 44 months). RESULTS: Post-radiosurgical imaging (PRI) changes
      developed in 30.5% of patients with regular follow-up magnetic resonance imaging,
      and were symptomatic in 10.7% of all patients at 7 years. PRI changes resolved
      within 3 years developed significantly less often (p = 0.0274) in patients with
      symptoms (52.8%) compared to asymptomatic patients (94.8%). The 7-year actuarial
      rate for developing persistent symptomatic PRI changes was 5.05%. Multivariate
      logistic regression modeling found that the 12 Gy volume was the only independent
      variable that correlated significantly with PRI changes (p < 0.0001) while
      symptomatic PRI changes were correlated with both 12 Gy volume (p = 0.0013) and
      AVM location (p = 0.0066). CONCLUSION: Complications from AVM radiosurgery can be
      predicted with a statistical model relating the risks of developing symptomatic
      post-radiosurgical imaging changes to 12 Gy treatment volume and location.

PMID- 9231671
TI  - Stereotactic radiosurgery for glomus jugulare tumors: a preliminary report.
AB  - PURPOSE: This study was conducted to evaluate the toxicity and efficacy of
      stereotactic radiosurgery treatment of glomus jugulare tumors. METHODS AND
      MATERIALS: Between March 1990 and January 1995, nine patients underwent
      stereotactic radiosurgery with the Leksell Gamma Knife Unit for glomus jugulare
      tumors. Previous treatment had failed in four patients. The seven female and two
      male patients had a median age of 67 years. RESULTS: The median time from
      stereotactic radiosurgery to the most recent clinical follow-up was 20 months
      (range 7-65 months). Subjectively, 7 of 9 patients noted a decrease in the
      intensity of their symptoms. Objectively, 8 of 9 tumors remained stable in size
      by serial magnetic resonance imaging scans and one was smaller. There was no
      acute or chronic toxicity. CONCLUSION: This early experience suggests that
      stereotactic radiosurgery is a promising treatment for glomus jugulare tumors.

PMID- 9231672
TI  - Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical
      experience in squamous cell carcinoma of the tonsillar fossa and soft palate.
AB  - PURPOSE: Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR)
      brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate
      (LDR) interstitial radiation therapy (IRT) schedules, have been developed for
      clinical use. This article reports the initial results using these novel
      schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or
      soft palate (SP). METHODS AND MATERIALS: Between 1990 and 1994, 38 patients with
      TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR
      brachytherapy, either alone or in combination with external irradiation (ERT).
      Half of the patients were treated with fr.HDR, which entailed twice-daily
      fractions of > or = 3 Gy. The other 19 patients were administered PDR, which
      consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative
      dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients
      treated by brachytherapy were compared to 72 patients with similar tumors treated
      in our institute with curative intent, using ERT alone. The median cumulative
      dose of ERT-only series was 70 Gy (range 40-77). RESULTS: Excellent locoregional
      control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38)
      developing local failure, and salvage surgery being possible in three of the
      latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP)
      significantly influenced local control rates. The type and severity of the side
      effects observed are comparable to those reported in the literature for LDR-IRT.
      These results contrast sharply with our ERT-only series, in which 39% of patients
      (28 of 72) developed local failure, with surgical salvage being possible only in
      three patients (11%). Taking the data set of 110 patients, in a univariate
      analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10
      (biological effective dose with a correction for the OTT) were significant
      prognostic factors for local relapse-free survival (LRFS) and overall survival
      (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and
      BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as
      well as for OS (p < 0.001 and 0.003, respectively). With regard to the current
      (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response
      relationships were established, significant, however, only for the BEDcor10 (p =
      0.03). CONCLUSION: The 3-year LRFS of approximately 90% for TF and SP tumors
      reported here is comparable with the best results in the literature, particularly
      given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors.
      When compared with our historical (ERT-only) controls, the patients treated with
      IRT had superior local control. A dose-response relationship was established for
      the BEDcor10.

PMID- 9231673
TI  - External beam radiation therapy for squamous cell carcinoma of the soft palate.
AB  - PURPOSE: External beam radiation therapy for carcinoma of the soft palate aims to
      achieve loco-regional control with normal speech, nasal function, swallowing
      mechanism, and minimal side effects such as nasal speech and regurgitation of
      food into the nasopharynx. In this report we present our results of radiotherapy
      in the treatment of 24 patients with squamous cell carcinoma of the soft palate.
      METHODS AND MATERIALS: A total of 24 patients with squamous cell carcinoma of the
      soft palate were treated at the Veterans Administration Medical Center
      Minneapolis, MN, between February 1977 and May 1992. Of the 24 patients 2 had T1,
      19 T2, 1 T3, and 2 had T4 lesions. Nineteen patients did not have clinical nodal
      disease, stage (N0), 1 had N1, 2 N2, and 2 N3 disease (Table 1). All the patients
      were treated by 4 MeV linear accelerator. A 1.75 Gy median dose was administered
      per fraction to a total of 70 Gy median dose. Bilateral opposed compensated
      shrinking fields technique was used. RESULTS: The 3-year disease free survival
      rate after external beam radiation therapy was 100% (1 out of 1), 64.7% (11 out
      of 17), 100% (1 out of 1), and 0%, for patients with T1, T2, T3, and T4 disease,
      respectively. Salvage surgery for recurrent disease was successful in 57.1% (4
      out of 7 patients (Table 2). The ultimate 3-year disease free survival rate for
      the entire group, including surgical salvage, was 81% (17 out of 21) (Fig 1).
      CONCLUSION: Radiation therapy alone in our institution resulted in tumor control
      and survival rates compare favorably to previously published reports in the
      literature. Surgery can be reserved as salvage procedure.

PMID- 9231674
TI  - Superior vena cava obstruction in small-cell lung cancer.
AB  - PURPOSE: To identify prognostic or treatment factors influencing the response of
      superior vena cava obstruction (SVCO), time to SVCO recurrence, and overall
      survival of SCLC patients with SVCO at presentation; and to assess the role of
      retreatment in patients with SVCO at recurrent or persistent disease. METHODS AND
      MATERIALS: Between January 1983 and November 1993, 76 consecutive patients who
      had small-cell lung cancer (SCLC) with SVCO were treated in our institution.
      Analysis was done according to the disease status at diagnosis of SVCO. The first
      analysis concerned a group of 50 patients who had SVCO at initial presentation.
      The second analysis concerned a group who had SVCO as a manifestation of
      persistent or recurrent disease. RESULTS: In the first analysis, 93% had
      significant improvement in symptoms of SVCO after chemotherapy and 94% after
      mediastinal radiation. Response is almost universal despite a wide range of
      radiation fractionation and total dose used. Seventy percent remained SVCO-free
      before death. Thirty percent developed recurrence of SVCO symptoms 1-16 months
      (median 8) after the start of initial treatment. Those who received combined
      chemotherapy and radiation had a longer time to SVCO recurrence (p = 0.018)
      compared to those who received chemotherapy alone. This effect is mainly seen in
      limited-stage patients. The presence of SVCO recurrence tends to have an adverse
      effect on the overall survival (p = 0.077) irrespective of the time when the
      recurrences occurred (p = 0.296). The median survival of this whole group of 50
      patients in the first analysis was 9.5 months, and the 2-year survival was 10%.
      Stage was strongly predictive of survival (p < 0.001). Sixteen percent (3 of 19)
      of the patients with limited-stage diseases were long-term survivors (two
      patients survived 35 months and one survived 70 months). The early mortality from
      SVCO was 2%. In the second analysis, 85% had previously been treated with
      chemotherapy alone. The response rate of SVCO in the analysable patients (n = 39)
      was 77%. There was no significant difference in the response rate of SVCO to
      treatment comparing patients treated by chemotherapy first or mediastinal
      radiation first (p = 0.653), but most patients [82% (32 of 39)] received
      radiation as the initially treatment of SVCO. Ninety-three percent (38 of 41)
      received mediastinal radiation as a part of their ultimate retreatment regimen,
      and 68% (28 of 41) received mediastinal radiation as their sole retreatment
      regimen. Thirty-two percent (13 of 41) received chemotherapy as a part of their
      ultimate retreatment regimen, and only 7% received chemotherapy alone as their
      sole retreatment regimen. Eighty-three percent (25 of 30) of those whose SVCO
      responded remained free of SVCO before death, with a median survival of 3 months
      after recurrent or persistent disease documented. CONCLUSION: Chemotherapy or
      mediastinal radiation is very effective as an initial treatment in SCLC patients
      with SVCO at presentation and at recurrent or persistent disease. There is no
      obvious need to use big radiation fraction sizes for the first few radiation
      treatment as was previously believed. In patients with recurrent or persistent
      SCLC with SVCO, especially in those who previously received chemotherapy only, we
      have more experience in incorporating mediastinal radiation as a major component
      of the palliative regimen with highly effective and durable palliation achieved.

PMID- 9231675
TI  - Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung
      cancer.
AB  - PURPOSE: Among patients with Stage I nonsmall cell lung cancer (NSCLC), those
      treated with conventional radiotherapy show poorer prognosis than those treated
      by surgery. To improve the prognosis of such patients, we have used
      hyperfractionated radiation therapy. METHODS AND MATERIALS: Between 1988 and
      1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy
      twice daily to a total dose of 69.6 Gy. All patients were technically operable,
      but 29 had medical problems and 20 refused surgery. The median age and Karnofsky
      Performance Status was 63 years and 90, respectively. No patient received
      chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not
      given. RESULTS: The median survival time was 33 months, and the 5-year survival
      rate was 30%. The rate at 5 years for freedom from each of relapse, local
      recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%,
      55%, 89%, and 75%, respectively. Univariate analysis revealed that higher
      Karnofsky Performance Status score, absence of weight loss before treatment, and
      T1 stage were associated with better survival, although the T stage became
      insignificant on multivariate analysis. There were two Grade 3 acute toxicities
      and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity.
      CONCLUSION: The results of this study compare favorably with those of most
      previous studies employing conventional fractionation. Further studies on
      hyperfractionation seem to be warranted for Stage I NSCLC.

PMID- 9231676
TI  - Impact of cradle immobilization on setup reproducibility during external beam
      radiation therapy for lung cancer.
AB  - PURPOSE: To compare the setup accuracy during fractionated radiation therapy for
      two patient groups with lung cancer treated with and without an immobilization
      cradle. METHODS: Three hundred ninety-seven port films from 30 patients
      immobilized in the Alpha Cradle were compared with 329 port films from 30
      patients who were not immobilized with the cradle. All patients were treated with
      curative intent for nonmetastatic lung cancer. The frequency of physician
      requested isocenter shifts were compared in the two groups using a two-tailed chi
      square test. Initial port films taken on the first day of treatment, routine
      films taken usually weekly during radiation therapy, and requested films taken
      after a requested shift were considered separately. The immobilization device
      consisted of a custom-made foam cradle that extended from above the head to the
      knees. Patients were generally treated with their arms above their heads, and
      treatment setup marks in the immobilized patients were placed on both the
      patients' skin and the immobilization cradle. For the noncradle patients, setup
      marks were placed only on the patients' skin. RESULTS: For the routine films, the
      frequency of physician-requested isocenter shifts was lower in immobilized
      patients than in the nonimmobilized group (p = 0.139). Most of this reduction was
      seen on oblique fields (p = 0.038). No benefits were seen among initial or
      requested films. The two groups were well balanced with regard to stage, age,
      field size, and total dose. CONCLUSIONS: The use of aggressive immobilization
      improves the setup reproducibility in patients receiving external beam radiation
      therapy for lung cancer, especially during treatment with oblique fields. This
      improvement in treatment accuracy might improve the therapeutic ratio.

PMID- 9231677
TI  - Does additional brachytherapy improve the effect of external irradiation? A
      prospective, randomized study in central lung tumors.
AB  - PURPOSE: Endobronchial brachytherapy has become more widely used to increase the
      total local dose of irradiation ("boost") applied for the treatment of lung
      cancer. Apart from treatment for local stenosis, endobronchial brachytherapy in
      combination with external irradiation (EI) has the potential to improve local
      tumor control and perhaps prolong survival, but the real benefit has not been
      proven yet. To evaluate the possible effects of external irradiation with an
      additional boost of high dose rate (HDR) brachytherapy, we conducted a
      prospective randomized study. METHODS AND MATERIALS: Design-two groups were
      compared: Group 1 was treated with external radiotherapy alone (planned dose 60
      Gy); Group 2 received an additional boost of HDR brachytherapy of scheduled 4.8
      Gy each (at 10 mm from the source axis) before and after external irradiation.
      Patients-98 patients with advanced inoperable lung cancer were included in the
      study, 42 in Group 1 and 56 in Group 2. Both groups were comparable with respect
      to age, sex, tumor stage, Karnofsky performance status (KPS), and histology.
      RESULTS: A mean total external irradiation dose of 50.5 +/- 14.1 Gy in Group 1
      and 50 +/- 12.5 Gy in Group 2 was applied. Group 2 received an additional dose of
      7.44 +/- 2.6 Gy (at 10 mm depth) through brachytherapy. The median survival time
      in both groups was comparable (28 weeks and 27 weeks, respectively). In patients
      with squamous cell carcinoma (68 patients) Group 2 showed an advantage in median
      survival with borderline significance (40 vs. 33 weeks, p = 0.09). Group 2 showed
      also a better local tumor control in all patients; patients with squamous cell
      carcinoma had a significantly longer period of local tumor control. Fatal
      hemoptysis was the cause of death in 6 (14.2%) patients in Group 1 and 11 (18.9%)
      in Group 2 (p = 0.53). CONCLUSIONS: High dose rate brachytherapy in patients with
      inoperable lung cancer increased local control in our randomized study when used
      in combination with external irradiation. Survival time was also longer, but with
      no clear statistical significance. This applied especially to patients with
      squamous cell carcinomas. There was no statistically significant difference in
      the incidence of fatal hemoptysis between the two groups.

PMID- 9231678
TI  - Long-term follow-up of axillary node-positive breast cancer patients receiving
      adjuvant systemic therapy alone: patterns of recurrence.
AB  - PURPOSE: Prognostic factors for locoregional failure have been poorly documented.
      The purpose of this retrospective review is to examine the patterns of failure of
      320 patients with Stage II or III axillary node-positive breast cancer who
      received adjuvant chemotherapy without locoregional radiation. METHODS AND
      MATERIALS: The records of 735 patients who were referred to the London Regional
      Cancer Centre between 1980 and 1989 with a diagnosis of Stage II or III breast
      cancer were reviewed. Three hundred and twenty patients were identified who
      underwent segmental mastectomy with axillary dissection or modified radical
      mastectomy and adjuvant chemotherapy without adjuvant locoregional radiation.
      Seventy-one percent of these patients had undergone a modified radical
      mastectomy, 40% had T1 tumors, 49% T2, and 11% T3. Resection margins were
      positive in 13 patients. The median number of axillary nodes removed was 11.
      Fifty-four percent had one to three positive axillary nodes, 27% had four to
      seven positive nodes, and 19% had in excess of seven positive nodes. RESULTS:
      Median follow-up for the 320 patients was 77 months. One hundred and fourteen
      patients developed a locoregional recurrence as the site of first relapse (31 in
      the intact breast, 29 on the chest wall, 21 in the axilla, 22 in the
      supraclavicular fossa, 1 in the internal mammary chain, and 10 in multiple
      sites). Thirty-three percent of segmental mastectomy patients and 13% of modified
      radical mastectomy patients developed local recurrence. Seven percent of patients
      recurred in axillary or supraclavicular nodes each. Factors with regard to
      locoregional recurrence which on univariate analysis were significant included
      type of mastectomy (i.e., segmental vs. modified radical), size of primary tumor,
      positive resection margins, and percentage of ideal chemotherapy dose intensity
      (< 66% vs. > or = 66%). After multivariate analysis, only type of mastectomy,
      size of primary tumor, and percentage of ideal chemotherapy dose intensity
      retained significance. The number of positive axillary nodes was not a
      significant factor. Number of positive axillary nodes plus the above four
      clinical factors were analyzed in terms of regional recurrence specifically. By
      univariate and multivariate analysis, only size of primary tumor retained
      significance. Again, the number of positive axillary nodes was not a relevant
      factor. CONCLUSION: Patients receiving adjuvant chemotherapy who are at high risk
      of locoregional recurrence include those who undergo segmental mastectomy and
      those with larger tumors (> 5 cm in diameter). Breast or chest wall radiation is
      recommended for these groups. Supraclavicular radiation is recommended for
      patients with tumors larger than 5 cm in diameter. Axillary recurrences were
      relatively infrequent in patients who had undergone an adequate Level I and II
      axillary dissection, and therefore, axillary radiation was not recommended.

PMID- 9231679
TI  - Extracapsular axillary node extension in patients receiving adjuvant systemic
      therapy: an indication for radiotherapy?
AB  - PURPOSE: This is a retrospective review into the patterns of failure of 82
      patients with Stage II or III breast cancer who had extracapsular extension (ECE)
      of axillary nodal metastases and who received systemic chemotherapy or hormonal
      therapy without loco-regional radiation. METHODS AND MATERIALS: The clinical
      records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III
      breast cancer seen at the London Regional Cancer Centre between 1980-1989 were
      reviewed. Patients were identified who underwent segmental mastectomy with
      axillary node dissection or modified radical mastectomy and received adjuvant
      chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two
      patients within this group had pathologic evidence of extracapsular axillary node
      extension (ECE). For 45 of these patients the extension was extensive, and for
      the remaining 37 it was microscopic. This ECE-positive group was compared to a
      subgroup of 172 patients who did not have pathologic evidence of extracapsular
      axillary node extension but had metastatic carcinoma confined within the nodal
      capsule. RESULTS: Median age of the 82 ECE-positive patients was 56 years. Twenty
      five patients had had a segmental mastectomy, the remainder a modified radical
      mastectomy. Median actuarial survival was 60 months, with a median disease-free
      and loco-regional failure-free survival of 38 months. Seventy-eight percent of
      these patients developed a recurrence, which was loco-regional in 60% (21% local,
      21% regional, 2% local and regional, and 16% loco-regional and metastatic). There
      was a 36% recurrence rate in intact breast, 14% the chest wall following modified
      radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and
      1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients
      with a group of 172 ECE-negative patients determined that there was a
      statistically significant difference between the two groups in terms of survival
      (overall and disease-free) and loco-regional recurrence. Univariate analysis of
      the entire 254 node-positive patient group revealed extracapsular nodal extension
      (ECE) to be a prognostically significant factor for actuarial and disease-free
      survival as well as for loco-regional failure, but ECE did not remain an
      independently prognostic factor after multivariate analysis. Segmental
      mastectomy, positive resection margins, and ER negative status increased the risk
      of loco-regional recurrence within the ECE-positive group. CONCLUSIONS:
      Extracapsular axillary node extension is a prognostically significant factor for
      actuarial survival, disease-free survival, and loco-regional failure but not
      independent of other adverse prognostic factors. It is a marker for increased
      loco-regional recurrence associated with doubling of breast, chest wall, and
      supraclavicular recurrence rates. The risk of axillary relapse in patients who
      have had an adequate level I and II axillary dissection but demonstrate
      extracapsular extension is low (7%). We recommend breast/chest wall and
      supraclavicular radiation for all patients with pathologic evidence of such
      extranodal extension who have had a level I and II axillary dissection regardless
      of the number of positive axillary nodes. Axillary irradiation should be
      considered for patients who have had only an axillary sampling or level I
      axillary dissection.

PMID- 9231680
TI  - A pilot study of concomitant boost accelerated superfractionated radiotherapy for
      stage III cancer of the uterine cervix.
AB  - PURPOSE: Retrospective studies suggest that prolonged treatment time adversely
      affects control rates of squamous carcinomas managed by radiotherapy. From 1989
      to 1994 a prospective clinical trial was conducted to assess the feasibility and
      efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy
      for advanced uterine cervical carcinoma. METHODS AND MATERIALS: Twenty newly
      diagnosed patients with FIGO stage III squamous cell carcinoma of the cervix were
      irradiated using a CBASF regimen. Patients received 45 Gy administered to the
      whole pelvis in 25 fractions in 5 weeks. On Monday, Wednesday, and Friday of the
      last 3 weeks, an additional 1.6 Gy boost was given 6 hours after the whole pelvis
      treatment. The 9 boost treatments, totaling 14.4 Gy, were given via lateral
      fields encompassing the parametria and primary tumor for a cumulative tumor dose
      of 59.4 Gy. A single low-dose rate brachytherapy procedure was performed within 1
      week after the external beam radiotherapy to raise the point A dose to 85-90 Gy
      in 42 days. Primary endpoints of analysis were local control, complications, and
      patterns of failure. Results are compared with the outcomes of 21 patients
      treated with conventionally fractionated (CF) radiotherapy during the same years.
      RESULTS: Median total treatment time was 46 days in the CBASF group (range 37
      62). Median follow-up interval among surviving CBASF patients is 3.8 years. The
      four-year actuarial local control rates are 78% and 70% in the CBASF and CF
      groups, respectively (p = ns). Only 2 CBASF patients required a treatment break
      because of acute toxicity, but severe late complications occurred in 8/20 CBASF
      patients for a crude rate of 40%. Distant failure was more common than local
      failure in the CBASF group, and para-aortic node failure occurred in six of the
      eight CBASF patients with distant failure. CONCLUSIONS: In the management of
      stage III cervix cancer, the CBASF regimen produced a trend toward improved local
      control when compared with the CF regimen, shifting the patterns of failure
      toward a higher rate of isolated distant failures. The high frequency of para
      aortic node failure warrants consideration of elective treatment to this region
      in stage III patients treated with curative intent. Although the high local
      control rate of the CBASF regimen supports further investigation of accelerated
      treatment regimens for locally advanced cervix cancer, the unacceptable risk of
      late complications necessitates refinement in technique and scheduling to improve
      the therapeutic ratio.

PMID- 9231681
TI  - Early stage prostate cancer treated with radiation therapy: stratifying an
      intermediate risk group.
AB  - PURPOSE: This study identifies two early prostate cancer populations within the
      T1/T2AB, Gleason 2-7, pretreatment prostate specific antigen (PSA) 4-15 ng/ml
      grouping. By demonstrating different outcomes we may be able to more
      appropriately select a subgroup for whom adjuvant therapy trials or altered
      treatment techniques are indicated. MATERIALS AND METHODS: One hundred forty-six
      patients with T1/T2AB, Gleason score 2-7, PSA 4-15 ng/ml prostate cancer were
      treated with external beam radiotherapy alone from November 1987 to October 1993.
      The median pretreatment PSA was 8.6 and the mean 8.7. Minimum follow-up was 2
      years with a median of 38 months (mean 42 months, range 24-87). The median age
      was 70 years (range 58-83) and the median central axis dose delivered was 7240
      cGy (mean 7273, range 6541-7895 cGy). Eleven patients received conventional
      radiotherapy while 135 were treated using conformal techniques. As there is
      evidence that a low PSA nadir is an early marker for long term biochemical
      control, time to post treatment PSA < 1 ng/ml was actuarially analyzed by Gleason
      score, pretreatment PSA, radiation dose, stage, and the presence of perineural
      invasion. Pretreatment PSA was the only patient characteristic predictive of
      achieving a PSA level < 1.0 ng/ml. Biochemical relapse free (bNED) control (non
      rising PSA) was then compared for patients above and below the approximate median
      pretreatment PSA level of 8 ng/ml. bNED control rates and the time to PSA < 1.0
      ng/ml were estimated using Kaplan-Meier methodology, and differences in bNED
      control and PSA < 1.0 ng/ml according to PSA level were evaluated using the log
      rank test. RESULTS: Results from actuarial analysis revealed that pretreatment
      PSA was the only significant variable predictive of a PSA < 1.0 ng/ml. Ninety
      eight percent of patients with pretreatment PSA < 8 achieved a PSA level < 1.0
      ng/ml within 3 years compared to 78% for patients with a PSA > 8 ng/ml (p =
      0.0003). bNED control for the two groups separated at a pretreatment PSA of 8
      ng/ml confirms a favorable outcome, 88% bNED control at 5 years for < 8 ng/ml and
      74% for a pretreatment PSA > or = 8 ng/ml (p = 0.007 for overall curve
      comparison). CONCLUSION: For early prostate cancer patients (T1/T2AB, Gleason 2
      7, pretreatment PSA 4-15) there is a significant break in bNED control following
      external beam radiation at a pretreatment PSA level of 8 ng/ml. Patients with
      pretreatment PSA < 8 have a very favorable bNED response with radiation alone
      while those with a pretreatment PSA 8-15 have a significant decrease in bNED
      response. The 27% failure rate at 5 years in the PSA 8-15 ng/ml patients may
      justify altered treatment techniques or clinical trials of adjuvant androgen
      deprivation in this group.

PMID- 9231682
TI  - Enhancement of prostate tumor volume definition with intravesical contrast: a
      three-dimensional dosimetric evaluation.
AB  - PURPOSE: To assess the impact of intravesical contrast during computed tomography
      (CT) simulation on prostate tumor volume definition and dose distribution.
      METHODS AND MATERIALS: Sixteen patients with localized adenocarcinoma of the
      prostate underwent CT-based virtual simulation in preparation for definitive
      radiotherapy. Patients were immobilized with a foam cradle and an initial CT was
      performed after oral but without intravesical contrast (noncontrast scan). A
      second scan was performed following administration of intravesical contrast
      (contrast scan). Beam apertures were designed on the noncontrast scans and
      digitized into the contrast scan file. Beam apertures were also designed on the
      contrast scans. Isodose plans were generated for several beam apertures and
      arrangements. RESULTS: There was enhanced visualization of the prostate at the
      cephalad portion of the field for 15 of the 16 cases. The mean differences
      between the noncontrast and contrast volumes was significant (p = 0.0001). The
      mean percent underdosage to the prostate ranged from 3.9% to 18.6%, depending
      upon the target volume and beam arrangement. CONCLUSION: This study demonstrates
      the necessity of using intravesical contrast for defining the location of the
      prostate during CT simulation. The underestimation of the extent of the prostate
      when omitting intravesical contrast leads to significant underdosage. The value
      of intravesical contrast is most evident when small (prostate only) conformal
      fields are used.

PMID- 9231683
TI  - Is combined modality therapy necessary for advanced Hodgkin's disease?
AB  - PURPOSE: To determine whether single-modality therapy is optimal management for
      patients with Stage III-IV Hodgkin's disease. METHODS AND MATERIALS: All patients
      with advanced (Stage III and IV) Hodgkin's disease treated at the University of
      Florida from 1964 through 1989 (n = 141) were studied retrospectively for factors
      predictive of good outcome with single-modality therapy. Treatment modalities
      varied and were distributed as follows: combined-modality therapy (CMT), 55
      patients; chemotherapy alone (CX), 50 patients; and radiotherapy alone (RT), 36
      patients. RESULTS: Ten-year rates of freedom from relapse and overall survival
      for all Stage III patients were 66% and 59% compared with 36% and 35% for Stage
      IV patients. The RT subset was highly selected with the majority of patients
      having nonbulky Stage IIIA disease. Within the RT group, multivariate analysis
      identified the degree of splenic involvement and age as the factors most
      associated with freedom from relapse. In patients treated with CX, multivariate
      analysis identified bulky tumor (maximum transverse tumor dimension > 6 cm) as
      the most important prognostic factor for relapse. In patients without bulky
      disease (< or = 6 cm), the probabilities of freedom from relapse and overall
      survival at 10 years, respectively, according to treatment group were 53% and 58%
      for RT patients, 60% and 56% for CX patients, and 83% and 71% for CMT patients.
      For patients without bulky disease, the probability of freedom from relapse was
      significantly better for the CMT group than for CX patients (p = 0.03) or RT
      patients (p = 0.04), but there was no statistical difference in overall survival
      among the three groups. In patients with bulky disease (> 6 cm), the
      probabilities of freedom from relapse and overall survival at 10 years were 44%
      and 45% for RT patients, 9% and 0% for CX patients, and 72% and 58% for CMT
      patients. Freedom from relapse and overall survival were significantly better (p
      = 0.0001) for CMT patients compared with CX patients. Fatal hematopoietic
      disorders developed in 10 patients: 2 of 36 RT patients, 2 of 50 CX patients, and
      6 of 55 CMT patients. Nine patients had received chemotherapy, and eight had six
      or more cycles of alkylator-based chemotherapy. CONCLUSION: This retrospective
      study suggests that combined-modality therapy is preferable to single-modality
      therapy in the majority of patients with advanced Hodgkin's disease.

PMID- 9231684
TI  - Long-term outcome of treatment for Ann Arbor Stage I Hodgkin's disease:
      prognostic factors for survival and freedom from progression.
AB  - PURPOSE: The earliest stages of Hodgkin's disease are associated with excellent
      short-term survival with radiation therapy. This has led to controversies
      regarding pretreatment evaluation, the extent of irradiation, the role of
      chemotherapy, and the relative importance of prognostic factors. Long-term
      results were sought to address these controversies. METHODS AND MATERIALS: A
      retrospective study was conducted of patients with Stage I Hodgkin's disease
      treated at the M. D. Anderson Cancer Center from 1967 through 1987. The median
      age at presentation of 145 patients was 31 years, and the male-to-female ratio
      was 1.8. Pretreatment evaluation included lymphangiography and bone marrow
      aspiration and biopsy in all patients. Laparotomy was performed in 101 of the 145
      patients (70%). There were 133 patients with supradiaphragmatic presentations; 12
      patients had infradiaphragmatic adenopathy. Only five patients had B symptoms
      (3.5%). Histologic subtypes of the disease included lymphocyte predominance
      17.9%, nodular sclerosis 40.7%, mixed cellularity 40.7%, and one unclassified
      Hodgkin's disease with primary splenic involvement. All patients were treated
      with radiotherapy, and 16 (11%) also received combination chemotherapy as part of
      their initial treatment. Radiotherapy techniques included involved/regional field
      in 49%, extended field in 42.7% (mantle or inverted Y), and subtotal nodal
      irradiation in 8.3%. Follow-up extended from a minimum of 30-339 months, with a
      median period of observation of 16.5 years. RESULTS: The median survival was 13.7
      years. The 10- and 20-year survival rates were 83% and 66%, respectively. The
      only factor important for decreased survival was age >40 years at diagnosis (p <
      0.0001). Out of 43 deaths, 11 were the result of Hodgkin's disease and the
      remaining 32 resulted from intercurrent disease, including treatment-related
      causes. Median freedom from progression was 10.5 years, and the 10- and 20-year
      freedom from progression were 76% and 69%, respectively. Out of 39 relapses, 5
      (13%) occurred beyond 10 years. Women had higher freedom from progression (p =
      0.0534) than men. Age, histology, bulk of disease, site of involvement including
      the mediastinal presentations, and the addition of chemotherapy did not influence
      the freedom of progression. Although very few patients (12 of 145) received
      subtotal nodal irradiation, the freedom from progression at 10 years was 91.7%
      for this group versus 64.7% for the group of patients who were treated with more
      limited techniques. CONCLUSION: Treatment with radiation therapy for patients
      with Stage I Hodgkin's disease leads to an excellent outcome, but patients
      require long-term surveillance as late relapses are not rare. Age is the only
      factor that affects survival, and gender marginally affects freedom from
      progression. Subtotal nodal irradiation may improve freedom from progression;
      further investigation of this treatment is justified.

PMID- 9231685
TI  - Palliation of AIDS-related primary lymphoma of the brain: observations from a
      multi-institutional database.
AB  - PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are
      presumed to have primary central nervous system lymphoma (PCNSL). To document the
      palliative efficacy of cranial irradiation (RT) relative to the endpoints of
      complete and overall response for the respective symptoms. METHODS: An analysis
      of 163 patients with AIDS-related PCNSL who were evaluated at nine urban
      hospitals was performed. These patients were treated for PCNSL after the
      establishment of a tissue diagnosis or on a presumptive basis after failing
      empiric treatment for toxoplasmosis. All patients were treated between 1983 and
      1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and
      steroids (>90% dexamethasone). Because multiple fractionation schemes were used,
      prescriptions were converted to biologically effective doses according to the
      formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha
      beta value of 10. RESULTS: The overall palliative response rate for the entire
      group was 53%. In univariate analysis, trends were present associating complete
      response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 =
      17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of
      higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20%
      vs. 5%). In multivariate analysis of factors predicting complete response, both
      higher KPS and higher BED retained independent significance. A separate
      univariate analysis identified high performance status (KPS > or = 70 vs. KPS <
      or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as
      factors significantly correlating with the endpoint of the overall response. In
      multivariate analysis, high performance status and the delivery of higher
      biologically effective doses of irradiation correlated significantly with higher
      overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from
      primary lymphoma of the brain can achieve some palliation from a management
      program that includes cranial irradiation. Young patients with excellent
      performance status are most likely to respond to treatment. The delivery of
      higher biologically effective doses of irradiation also may increase the
      probability of achieving a palliative response.

PMID- 9231686
TI  - Radiation treatment in patients with recurrent Kimura's disease.
AB  - PURPOSE: To assess the benefits of radiotherapy for patients with recurrent
      Kimura's disease and to document the role of radiation treatment as a successful
      mode of therapy. METHODS AND MATERIALS: From 1985 to 1991, a total of 26 patients
      with Kimura's disease were treated by local excision and/or systemic steroids at
      Yonsei University, Yonsei Cancer Center Hospital. Seventeen patients among them
      eventually had local recurrence after surgical excision. The 17 patients with
      recurrent Kimura's disease were divided into two groups on the basis of those who
      received radiation treatment and those who did not. Eight patients in the
      nonradiation group were treated by systemic steroids alone with individualized
      doses and schedules. The remaining nine patients in the radiation group were
      treated by external beam irradiation. The prescribed radiation doses varied from
      21.6 to 45 Gy. A comparative analysis on treatment results between both groups
      was undertaken retrospectively. RESULTS: The majority of the recurrent cases in
      the nonradiation group treated by steroids alone experienced rapid rerecurrence
      of the disease. In contrast, all of the patients except one case in the radiation
      group achieved excellent local control with moderate doses of radiation. There
      was a significant difference in the rerecurrence rate between the patients of the
      radiation group (11%) and the nonradiation group (75%). No clear dose-response
      relationship could be derived from the patients of the radiation group. No
      secondary malignancies in the irradiated areas have been observed. CONCLUSION:
      Our results suggest that radiation treatment is preferable as an alternative
      option for patients with recurrent Kimura's disease who have failed to achieve
      local control by other modalities.

PMID- 9231687
TI  - Potential benefits of eliminating planning target volume expansions for patient
      breathing in the treatment of liver tumors.
AB  - PURPOSE: To investigate potential benefits derived from reduction or elimination
      of planning target volume (PTV) margins associated with patient breathing through
      examination of hepatic tumors treated with conformal therapy. METHODS AND
      MATERIALS: We reviewed the treatment plans of 50 patients who had previously
      received conformal partial organ liver irradiation for treatment of hepatic
      malignancies. PTVs for these plans included expansions (1-2 cm) for patient
      breathing. Data consisted of the three-dimensional dose distributions computed
      for the conformal plans generated for these volumes, and also for plans using
      identical beam arrangements but smaller block margins to treat planning target
      volumes that did not include the expansions for breathing. We calculated
      effective volumes (V(eff)) and normal tissue complication probabilities (NTCP)
      using dose-volume histograms for normal liver and analyzed changes in: V(eff),
      NTCP at the prescription dose, doses associated with selected NTCP levels, and
      tumor control probabilities (TCP) at these new dose levels. RESULTS: Elimination
      of the patient breathing components of the PTVs for these conformal treatments of
      liver tumors: (a) decreased the average V(eff) by 5%; (b) decreased the average
      predicted NTCP at the prescription (isocenter) dose used to treat the patients by
      4.5%; (c) increased the average target volume (isocenter) dose associated with
      low (1-10%) predicted normal liver NTCP by 6-8 Gy, which corresponded to (d) a
      predicted average 6-7% increase in TCP for aggressive liver tumors. Plans with
      PTV expansions for breathing that occurred mostly within the liver showed
      greatest potential benefit. CONCLUSIONS: Elimination of the margin added to
      hepatic target volumes for patient ventilation could lead to clinically
      meaningful increases in dose without increasing the predicted frequency of
      complications.

PMID- 9231688
TI  - Hyperbaric oxygen treatment for radiation proctitis.
AB  - PURPOSE: Our objective was to assess, retrospectively, the efficacy of hyperbaric
      oxygen treatment in radiation proctitis in all patients who have completed
      treatment for this disease at the Fremantle Hyperbaric Oxygen Unit. This unit is
      the only one of its kind in Western Australia. METHODS AND MATERIALS: Patients
      were assessed by a review of hospital records, blood bank records, and clinic
      review (if this was convenient), and all patients responded to a telephone
      survey. Patients were questioned regarding radiation proctitis symptoms and the
      degree to which each had improved. RESULTS: Most patients had previously been
      treated with radiotherapy for prostate carcinoma. Patients with proctitis mainly
      suffered from bleeding, diarrhoea, incontinence, and pain. In more than half of
      these patients, symptoms partially or completely resolved after hyperbaric oxygen
      treatment. CONCLUSION: Radiation-induced proctitis is a difficult clinical
      problem to treat and will probably become more significant with the rising
      incidence of diagnosis of prostate cancer. Hyperbaric Oxygen should be considered
      in the treatment of radiation-induced proctitis. Further prospective trials with
      strict protocol guidelines are warranted.

PMID- 9231689
TI  - Effect of radiation and paclitaxel on p53 expression in murine tumors sensitive
      or resistant to apoptosis induction.
AB  - PURPOSE: Tumors are thought to differ in their response to cytotoxic agents for a
      variety of reasons including cell cycle kinetics, degree of hypoxia, differential
      repair, and ability to survive when stressed. Our previous studies showed that
      murine mammary carcinoma MCA-4 tumors are relatively sensitive to both radiation
      and paclitaxel and exhibit a significant apoptotic response following treatment
      in vivo. In contrast, murine squamous cell carcinoma SCC-VII tumors are
      relatively resistant to radiation and paclitaxel and exhibit relatively little
      apoptosis following treatment. Since dysfunctional p53 has been shown to be
      associated with tumor resistance, perhaps through a dysregulated cell loss
      mechanism, we examined the role of p53 expression in the differential apoptotic
      response of these two tumors following cytotoxic treatment in vivo. METHODS AND
      MATERIALS: Mice bearing 8-mm tumors were treated with 40 mg/kg paclitaxel i.v. or
      15 Gy local tumor irradiation, and tumors were harvested at several time points
      up to 2 days following treatment. Histological sections of the tumors were then
      assessed micromorphometrically for mitotic arrest and apoptosis and
      immunohistochemically for p53 and p21 expression. RESULTS: In the apoptosis
      sensitive MCA-4 tumors, p53 expression increased rapidly following radiation from
      13% at baseline to a peak of 45% within 3 h, and expression remained elevated for
      more than 24 h. Radiation also upregulated p21 suggesting that radiation-induced
      apoptosis in MCA-4 tumor is p53 dependent. Paclitaxel also induced an increase in
      both p53 and p21 expression in MCA-4 cells; however, the increase was delayed
      compared to that after irradiation. This upregulation occurred after the onset of
      apoptosis which would suggest that paclitaxel-induced apoptosis is p53
      independent. Both radiation and paclitaxel caused p53 upregulation in the
      apoptosis-resistant SCC-VII tumors. The untreated SCC-VII tumor has 25% cells p53
      positive and has a very high level of p21 (87% cells positive) which suggests a
      downstream defect in p53 response. CONCLUSION: These results show that tumor
      responsiveness to paclitaxel and radiation, measured by tumor growth delay, was
      associated with apoptotic response. However, although both agents upregulated p53
      expression in these tumors, the association between this upregulation and
      induction of apoptosis was not clear. Additional studies using these and other
      tumors are warranted to elucidate the role of p53 and its downstream effectors in
      the in vivo responsiveness of tumors to paclitaxel and radiation.

PMID- 9231690
TI  - Calculation of integrated biological response in brachytherapy.
AB  - PURPOSE: To present analytical methods for calculating or estimating the
      integrated biological response in brachytherapy applications, and which allow for
      the presence of dose gradients. METHODS AND MATERIALS: The approach uses linear
      quadratic (LQ) formulations to identify an equivalent biologically effective dose
      (BEDeq) which, if applied to a specified tissue volume, would produce the same
      biological effect as that achieved by a given brachytherapy application. For
      simple geometrical cases, BED multiplying factors have been derived which allow
      the equivalent BED for tumors to be estimated from a single BED value calculated
      at a dose reference point. For more complex brachytherapy applications a voxel-by
      voxel determination of the equivalent BED will be more accurate. Equations are
      derived which when incorporated into brachytherapy software would facilitate such
      a process. RESULTS: At both high and low dose rates, the BEDs calculated at the
      dose reference point are shown to be lower than the true values by an amount
      which depends primarily on the magnitude of the prescribed dose; the BED
      multiplying factors are higher for smaller prescribed doses. The multiplying
      factors are less dependent on the assumed radiobiological parameters. In most
      clinical applications involving multiple sources, particularly those in
      multiplanar arrays, the multiplying factors are likely to be smaller than those
      derived here for single sources. The overall suggestion is that the
      radiobiological consequences of dose gradients in well-designed brachytherapy
      treatments, although important, may be less significant than is sometimes
      supposed. The modeling exercise also demonstrates that the integrated biological
      effect associated with fractionated high-dose-rate (FHDR) brachytherapy will
      usually be different from that for an "equivalent" continuous low-dose-rate
      (CLDR) regime. For practical FHDR regimes involving relatively small numbers of
      fractions, the integrated biological effect to tissues close to the treatment
      sources will be higher with HDR than for LDR. Conversely, the integrated
      biological effect on structures more distant from the sources will be less with
      HDR. This provides quantitative confirmation of an idea proposed elsewhere, and
      suggests the existence of a potentially useful biological advantage for HDR
      brachytherapy delivered in relatively small fraction numbers and which is not
      apparent when considering radiobiological effect only at discrete reference
      points. CONCLUSION: The estimation and direct calculation of integrated
      biological response in brachytherapy are both relatively straightforward.
      Although the tabular data presented here result from considering only simple
      geometrical cases, and may thus overestimate the consequences of dose gradients
      in multiplanar clinical applications, the methods described may open the way to
      the development of more realistic radiobiological software, and to more
      systematic approaches for correlating physical dose and biological effect in
      brachytherapy.

PMID- 9231691
TI  - Selection of coplanar or noncoplanar beams using three-dimensional optimization
      based on maximum beam separation and minimized nontarget irradiation.
AB  - PURPOSE: The design of an appropriate set of multiple fixed fields to achieve a
      steep dose gradient at the tumor edge, with minimal normal tissue exposure, is a
      very difficult problem, since a virtually infinite number of possible beam
      orientations exists. In practice we have selected beams in an iterative and often
      time-consuming process. This work proposes an optimization method, based on
      geometric and dose elements, to effectively arrive at a set of beam orientations.
      METHODS AND MATERIALS: Beams are selected by minimizing a goal function including
      an angle function (beam separation for steep dose gradient at target edge) and a
      length function (related to normal tissue dose volume histogram). The relative
      importance of these two factors may be adjusted depending on the clinic
      situation. The model is flexible and can include case specific practical anatomic
      and physical considerations. RESULTS: In extremely simple situations, the goal
      function yields results consistent with well-known analytical solutions. When
      applied to more complex clinical situations, it provides clinically reasonable
      solutions similar to those empirically developed by the clinician. The
      optimization process takes approximately 25 min on a UNIX workstation.
      CONCLUSION: The optimization scheme provides a practical means for rapidly
      designing multiple field coplanar or noncoplanar treatments. It overcomes
      limitations in human three-dimensional visualization such as trying to visualize
      beam directions and keeping track of the hinge angle between beams while
      accounting for anatomic/machine constraints. In practice, it has been used as a
      starting point for physicians to make modifications, based on their clinical
      judgment.

PMID- 9231693
TI  - Estimates of whole-body dose equivalent produced by beam intensity modulated
      conformal therapy.
AB  - PURPOSE: To estimate the dose delivered to patients by photons and neutrons
      outside the radiation fields when beam intensity modulation conformal
      radiotherapy is given. These estimates are then used to compute the risk of
      secondary cancers as a sequela of the radiation therapy. MATERIALS AND METHODS:
      The x-ray and neutron leakage accompanying two beam-intensity modulation
      techniques delivered by currently available linear accelerators were estimated
      for 6-MV, 18-MV, and 25-MV x-ray energies. Estimates of whole-body dose
      equivalents were determined using leakage measurements reported in the literature
      and treatment parameters derived for two modulated beam-intensity conformal
      therapy techniques. Risk values recommended by the National Council on Radiation
      Protection and Measurements (NCRP) were used to estimate the resulting risk of
      fatal radiation-induced cancer for 70.00 Gy prescribed tumor doses. RESULTS: The
      computed worst-case risks of secondary cancers increased in the range from 1.00%
      for 6-MV x-rays to 24.4% for 25-MV x-rays. CONCLUSIONS: Careful consideration
      should be made of the risks associated with secondary whole-body radiation before
      implementation of beam intensity modulated conformal therapy at x-ray energies
      greater than 10 MV.

PMID- 9231692
TI  - Whole body doses from linear accelerator-based stereotactic radiotherapy.
AB  - PURPOSE: The objective of this work was to measure whole body radiation doses in
      a humanoid phantom from linear accelerator-based cranial stereotactic
      radiosurgery/therapy (SRS/T), using different beam arrangements. METHODS AND
      MATERIALS: A standard noncoplanar five-arc beam arrangement and a four-arc
      technique without a sagittal arc were used to deliver 20 Gy in a single fraction
      to a midline spherical target volume in the corpus callosum region of an Alderson
      Rando anthropomorphic phantom using (i) a 20-mm and (ii) a 40-mm circular
      collimator. Whole body dose measurements were made using lithium fluoride
      thermoluminescent dosimetry. Whole body isodose plots in the sagittal and coronal
      planes and organ doses were compared for the two arcing beam arrangements. An
      ionization chamber was used to record the exit dose at intervals along the length
      of the phantom at midline and 4.5 cm off-axis for (i) a single fixed field and
      (ii) a solitary 90 degrees sagittal arc using a 40-mm circular collimator.
      RESULTS: The sagittal arc was the major contributor to neck and trunk doses when
      the five- and four-arc arrangements were compared, with fourfold greater thyroid
      dose. The gonad dose was increased by the sagittal arc, but was largely due to
      leakage radiation. The dose from a fixed field exiting down the long axis of the
      phantom was tenfold greater than that from a solitary 90 degrees sagittal arc.
      When the fixed field or arc traversed the lung or exited through the pharynx and
      major upper airways, the dose measurements below the diaphragm were 30-40% higher
      than those along the exit path of maximum soft tissue density. CONCLUSION: When
      SRS/T is used in nonmalignant conditions such as cranial arteriovenous
      malformations or benign tumors the exit paths of arcing beams or fixed fields
      should be taken into account when deciding upon the final treatment plan. Such
      consideration should minimize the risk of radiation-induced malignancy, notably
      in the thyroid gland of younger patients.

PMID- 9231694
TI  - Requiring institutions to inform participants who have completed therapy on SWOG
      8892 (RT +/- cisplatin for nasopharyngeal cancer) about early study closure:
      right idea, wrong patients.

PMID- 9231695
TI  - Regarding Chao et al. IJROBP 33(4):831-835; 1995.

PMID- 9231696
TI  - Neither platelet activating factor nor leukotrienes are critical mediators of
      liver injury after lipopolysaccharide administration.
AB  - The intravenous administration of lipopolysaccharide (LPS) to rats results in
      liver lesions characterized by the infiltration of both platelets and neutrophils
      into the liver and by midzonal hepatocellular necrosis. The liver injury is
      dependent on neutrophils, platelets and the coagulation system, as removal or
      inhibition of any of these components inhibits the development of hepatocellular
      necrosis. Platelet activating factor (PAF) and the cysteinyl leukotrienes (LTs)
      are potent inflammatory lipids that are critical for the development of some LPS
      mediated alterations. To test the hypothesis that PAF, alone or in combination
      with LTs, contributes to the development of liver injury during LPS exposure, we
      conducted studies with the PAF receptor antagonist, WEB 2086, and the 5
      lipoxygenase inhibitor, Zileuton. Female, Sprague-Dawley rats were pretreated
      with WEB 2086 (10 mg/kg, i.p.) alone or with Zileuton (40 mg/kg, p.o.) 1 h before
      the administration of LPS (4 mg/kg, i.v.) or its saline vehicle. Treatment with
      WEB 2086, alone or in combination with Zileuton, did not inhibit LPS-mediated
      hepatic neutrophil infiltration or liver injury, as assessed by histologic
      evaluation and increases in plasma alanine aminotransferase activity.
      Pretreatment with these agents also had no effect on the activation of the
      coagulation system or on the thrombocytopenia induced by LPS. These results
      suggest that PAF, alone or in combination with 5-lipoxygenase products, is not a
      critical mediator of LPS-induced hepatocellular injury in this model.

PMID- 9231697
TI  - Maternal and developmental toxicity of polychlorinated diphenyl ethers (PCDEs) in
      Swiss-Webster mice and Sprague-Dawley rats.
AB  - Polychlorinated diphenyl ethers (PCDEs) are industrial byproducts found in many
      ecosystems at low levels. PCDEs are not markedly toxic to adult rodents, but
      their developmental toxicity has not previously been examined. We evaluated the
      maternal and perinatal toxicity of nine PCDE congeners to outbred mice when
      compounds were administered from gestation day (GD) 6 through GD 15.
      2,2',4,4',5,6'-hexaCDE and 2,3',4',6-tetraCDE decreased the number of pups born
      per female mated and the number of pups surviving per litter born. 2,2',4,4',5,5'
      hexaCDE and 2,2',4,5,6'-pentaCDE decreased the number of litters born per female
      mated, without decreasing postnatal survival. The other PCDEs did not decrease
      survival either pre- or postnatally. None of the PCDEs caused absence of
      Harderian glands in surviving offspring at the doses administered. Neither
      induction of cytochromes P450 nor tissue residues of individual congeners
      correlated well with developmental toxicity. Three PCDEs were also evaluated in
      outbred (Sprague-Dawley) rats: 2,2',4,5,6'-pentaCDE and 2,3',4',6-tetraCDE,
      because of their toxicity to mice; 2,2',4,4',5,5'-hexaCDE, because it should
      exhibit PCB-like toxicity. Each congener was administered at three dose levels
      from GD 6 through GD 15. 2,2',4,5,6'-pentaCDE decreased the number of litters
      born at 100 mg/kg/day, and the survival of pups in litters carried to term, at
      both 50 and 100 mg/kg per day. Postnatal weight gain was also reduced. In
      contrast to its action in mice, 2,3',4',6-tetraCDE decreased neither the numbers
      of litters born nor postnatal survival of rat offspring, but did suppress
      postnatal weight gain at least through PD 5. As in mice, induction of cytochromes
      P450 was not well correlated with the developmental toxicity of individual
      congeners.

PMID- 9231698
TI  - Study of the effects of theophylline-related changes in total, free, short- chain
      acyl and long-chain acyl carnitine concentrations in rat heart.
AB  - This study is conducted to investigate the effect of oral theophylline
      administration on total (TC), free (FC), short-(SC), long-chain acyl (LC), acyl
      (AC) carnitine concentrations and acyl to free carnitine (AC/FC) ratio in rat
      heart. Theophylline was administrated at 100 mg/kg wt/day, and effects were
      monitored after a treatment period that lasted between a week and five weeks. The
      results indicated that theophylline feeding leads to significantly higher
      concentrations of TC, FC, SC, LC and AC in heart tissue as compared to those of
      control and placebo groups (P < 0.001). Moreover, the ratio of AC/FC was
      significantly increased (P < 0.001) as compared to either control or placebo
      groups. These changes may result from theophylline-enhanced mobilization of
      lipids from adipose tissues, which consequently stimulates an increased carnitine
      transport into the heart tissues to form fatty acylcarnitines for subsequent beta
      oxidation inside the heart mitochondria.

PMID- 9231699
TI  - Tolerance to the hypothermic and hyperthermic effects of chlorpyrifos.
AB  - Hypothermia is a commonly reported thermoregulatory response in rodents acutely
      exposed to organophosphates (OP); however, our laboratory has recently found a
      delayed hyperthermic response following the initial hypothermia when exposed to
      the OP, chlorpyrifos. It is well known that rodents display tolerance to OP
      induced hypothermia but little is known about tolerance to OP-induced
      hyperthermia. Twenty female rats of the Long-Evans strain were made tolerant to
      chlorpyrifos by administering 0 or 10 mg/g chlorpyrifos by gavage daily for four
      days. Core temperature (T[c]) and motor activity (MA) were monitored continuously
      by telemetry. Twenty-four hours after the fourth 10 mg/kg injection, the animals
      were administered a challenge dose of 25 mg/kg chlorpyrifos or corn oil while the
      telemetry data were monitored for the next 72 h. Non-tolerant rats displayed an
      initial hypothermic response with reduced MA followed by a delayed increase in
      T(c) 24 h after exposure. The tolerant animals displayed a blunted hypothermic
      response with virtually no change in MA, but a delayed increase in T(c) similar
      to that of non-tolerant animals. The hyperthermic response of the non-tolerant
      animals persisted for two days, whereas the tolerant animals recovered by the
      second day. The data indicate that tolerance to the hypothermic and hyperthermic
      effects of chlorpyrifos involve separate neurochemical pathways.

PMID- 9231700
TI  - Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice
      treated with toxic doses of paracetamol.
AB  - Paracetamol, in toxic doses, is associated with extensive liver damage. This
      represents one of the common causes of morbidity and mortality in drug poisoning
      cases. This study was undertaken to investigate the possible potentiation of the
      hepatoprotective action of N-acetylcysteine (NAC) by cimetidine (CMD), an
      inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine
      and the two in combination, administered 2 h post-paracetamol dose, on mortality,
      plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase
      activities and hepatic reduced glutathione (GSH) levels were investigated in mice
      24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC
      and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT
      activities. In addition, they prevented the depletion of hepatic GSH contents.
      However, concomitant administration of NAC and cimetidine produced a 100%
      survival rate and a marked reduction in plasma GOT and GPT activities to within
      the normal range, while significantly raising hepatic GSH concentrations to
      values close to those measured in saline-treated control animals. It is therefore
      concluded that cimetidine and N-acetylcysteine may have an additive
      hepatoprotective action in the treatment of paracetamol overdose.

PMID- 9231702
TI  - Transport of iron in the blood-brain-cerebrospinal fluid system.
AB  - Iron is an important constituent in brain and, in certain regions, e.g., the
      basal nuclei, reaches concentrations equivalent to those in liver. It has a role
      in electron transfer and is a cofactor for certain enzymes, including those
      involved in catecholamine and myelin synthesis. Iron in CSF is likely to be
      representative of that in interstitial fluid of brain. Transferrin in CSF is
      fully saturated, and the excess iron may be loosely bound as Fe(II). Brain iron
      is regulated in iron depletion, suggesting a role for the blood-brain barrier
      (BBB). Iron crosses the luminal membrane of the capillary endothelium by receptor
      mediated endocytosis of ferric transferrin. This results in an initial linear
      uptake of radioactive iron into brain at an average rate relative to serum of
      about 3.3 x 10(-3) ml x g of brain(-1) x h(-1) in the adult rat. This corresponds
      to about 80 nmol x kg(-1) x h(-1). Much higher rates occur in the postnatal rat.
      These increase during the first 15 days of life and decline thereafter. Within
      the endothelium, most of the iron is separated from transferrin, presumably by
      the general mechanism of acidification within the endosome. Iron appears to be
      absorbed from the vesicular system into cytoplasm and transported across the
      abluminal plasma membrane into interstitial fluid as one or more species of low
      molecular weight. There is some evidence that ionic Fe(II) is involved. Certainly
      Fe(II) ions presented on the luminal side rapidly cross the complete BBB, i.e.,
      luminal and abluminal membranes. Within interstitial fluid, transported iron will
      bind with any unsaturated transferrin synthesized or transported into the brain
      CSF system. Oligodendrocytes are one site of synthesis. From interstitial fluid,
      ferric transferrin is taken up by neurones and glial cells by the usual receptor
      mediated endocytosis. Calculations of the amount of iron leaving the system with
      the bulk flow of CSF indicate that most iron entering brain across the capillary
      endothelium finally leaves the system with the bulk outflow of CSF through
      arachnoid villi and other channels. A system in which influx of iron into brain
      is by regulated receptor-mediated transport and in which efflux is by bulk flow
      is ideal for homeostasis of brain iron.

PMID- 9231701
TI  - Glutathione peroxidase and catalase modulate the genotoxicity of arsenite.
AB  - The X-ray hypersensitive Chinese hamster ovary (CHO) cells, xrs-5, are also more
      sensitive to sodium arsenite in terms of cell growth and micronucleus induction
      than CHO-K1 cells. Since reactive oxygen species are suggested to be involved in
      arsenic toxicity, we have measured antioxidant mechanisms in xrs-5 as well as CHO
      K1 cells. There were no apparent differences in the activities of superoxide
      dismutase, glutathione S-transferase, glutathione reductase, and the levels of
      glutathione between xrs-5 and CHO-K1 cells. However, the activities of
      glutathione peroxidase and catalase were 5.4- and 5.8-fold lower, respectively,
      in xrs-5 cells. The addition of catalase or glutathione peroxidase to cultures
      reduced the arsenite-induced micronuclei in xrs-5 cells. Whereas, simultaneous
      treatment with mercaptosuccinate, an inhibitor of glutathione peroxidase, and 3
      aminotriazole, an inhibitor of catalase, synergistically increased the arsenite
      induced micronuclei. These results suggest that both catalase and glutathione
      peroxidase are involved in defense against arsenite genotoxicity. The xrs-6
      cells, another line of x-ray hypersensitive CHO cells, which had 1.6-fold higher
      catalase activity and 2.5-fold higher glutathione peroxidase activity than xrs-5
      cells, were also more sensitive than CHO-K1 cells but were less sensitive than
      xrs-5 cells to cell growth inhibition of arsenite. Moreover, a 1.6-fold increase
      of glutathione peroxidase activity by selenite adaptation effectively removed the
      arsenite-induced micronuclei in CHO-K1 cells. These results suggest that
      glutathione peroxidase is more important than catalase in defending against
      arsenite toxicity. Our results also suggest that increasing the intracellular
      antioxidant level may have preventive or therapeutic effects in arsenic
      poisoning.

PMID- 9231703
TI  - Cloning, characterization, and expression of a calcitonin receptor from guinea
      pig brain.
AB  - A calcitonin receptor was cloned from guinea pig brain by using a degenerate
      reverse transcription-polymerase chain reaction (RT-PCR) strategy. When the
      cloned guinea pig calcitonin receptor was transfected into COS 1 cells, salmon
      calcitonin stimulated intracellular cyclic AMP accumulation with an EC50 of 0.1
      nM, whereas human calcitonin was >250-fold less potent (EC50 27.6 nM). Related
      neuropeptides rat alphaCGRP and rat amylin did not activate the guinea pig
      calcitonin receptor at physiologic concentrations. Stimulation of the transfected
      guinea pig calcitonin receptor by salmon calcitonin also resulted in
      phosphatidylinositol hydrolysis with an EC50 of 2.5 nM. Expression of the
      calcitonin receptor was mapped by a combination of RT-PCR, northern analysis, and
      expression in Xenopus oocytes. The guinea pig calcitonin receptor was most highly
      expressed in diencephalon and a single subtype was detected.

PMID- 9231704
TI  - Subfamily of olfactory receptors characterized by unique structural features and
      expression patterns.
AB  - The complex chemospecificity of the olfactory system is probably due to the large
      family of short-looped, heptahelical receptor proteins expressed in neurons
      widely distributed throughout one of the several zones within the nasal
      neuroepithelium. In this study, a subfamily of olfactory receptors has been
      identified that is characterized by distinct structural features as well as a
      unique expression pattern. Members of this receptor family are found in mammals,
      such as rodents and opossum, but not in lower vertebrates. All identified
      subtypes comprise an extended third extracellular loop that exhibits amphiphilic
      properties and contains numerous charged amino acids in conserved positions.
      Olfactory sensory neurons expressing these receptor types are segregated in small
      clusters on the tip of central turbinates, thus representing a novel pattern of
      expression for olfactory receptors. In mouse, genes encoding the new subfamily of
      receptors were found to be harbored within a small contiguous segment of genomic
      DNA. Based on species specificity as well as the unique structural properties and
      expression pattern, it is conceivable that the novel receptor subfamily may serve
      a special function in the olfactory system of mammals.

PMID- 9231705
TI  - Demonstration of an E-box and its CNS-related binding factors for transcriptional
      regulation of the mouse type 1 inositol 1,4,5-trisphosphate receptor gene.
AB  - The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) is expressed abundantly
      in the CNS, such as in cerebellar Purkinje cells and the hippocampus. We
      established a tissue-specific cell-free transcription system and studied
      regulatory properties of the 5' upstream region of the IP3R1 gene by use of this
      system. Deletion analyses of the promoter revealed several cis elements that
      function significantly in brain nuclear extracts. Among those elements, sequences
      from -398 to -295 showed the most predominant cerebellum-specific positive
      function. Footprint analyses demonstrated a factor-binding region from -334 to 
      318, termed box-I, that contained an E-box consensus sequence. Electrophoretic
      mobility shift assay revealed CNS-related basic helix-loop-helix proteins for the
      box-I. Mutational studies using the function assay and competitive
      electrophoretic mobility shift assays demonstrated a good correlation between the
      box-I-binding factors and the activated transcription. Box-I-binding factors were
      present abundantly in adult mouse CNS, whereas their existence was restricted in
      embryonic and nonneural tissues. Transient chloramphenicol acetyltransferase
      assay for the IP3R1 promoter revealed the requirement of box-I in Neuro2a
      neuroblastoma cells. In the postnatal CNS, multiple basic helix-loop-helix
      factors are expressed abundantly, some of which are suggested to activate IP3R1
      gene expression in the mammalian CNS.

PMID- 9231706
TI  - Cloning and localization of exon 5-containing isoforms of the NMDAR1 subunit in
      human and rat brains.
AB  - Nine isoforms of the rat NMDAR1 receptor subunit have been previously identified,
      of which several have an alternatively spliced N-terminal insert believed to be
      important in proton sensitivity of the receptor. The cloning of the human
      homologues of NMDAR1-3b (hNMDA1-1) and NMDAR1-4b (hNMDA1-2), both bearing the
      insert, is reported here. A monoclonal antibody generated against the N-terminal
      region of these isoforms showed reactivity with at least two distinct human brain
      proteins of approximately 115 kDa. This antibody was further characterized by
      using a series of truncated fusion proteins and splice variants of NMDAR1
      demonstrating its specific recognition of an epitope within the 21-amino acid N
      terminal insert, encoded by exon 5. Western blot and immunocytochemical studies
      were performed to examine the expression of the exon 5-containing isoforms of the
      NMDAR1 subunit in both rat and human brain.

PMID- 9231707
TI  - Polysialic acid synthase (ST8Sia II/STX) mRNA expression in the developing mouse
      central nervous system.
AB  - A comparative study was undertaken to correlate the immunohistochemical
      localization of polysialic acid (PSA) and the in situ localization of ST8Sia II
      mRNA. In situ hybridization of postnatal day 3 mouse brain showed high levels of
      ST8Sia II mRNA expression in the cerebral neocortex, striatum, hippocampus,
      subiculum, medial habenular nucleus, thalamus, pontine nuclei, and inferior
      colliculus; intermediate-level expression in the olfactory bulb, hypothalamus,
      superior colliculus, and cerebellum; and low-level expression in other regions.
      The distribution of ST8Sia II mRNA in the neocortex and cerebellum coincided with
      the immunohistochemical localization of PSA. During brain development, ST8Sia II
      mRNA started decreasing and had almost disappeared by postnatal day 14.
      Comparison between ST8Sia II and IV mRNA expression was also undertaken by
      northern blot analysis and competitive PCR analysis. During the late embryonic to
      early postnatal stages of the mouse CNS, the ST8Sia II mRNA showed abundant mRNA
      expression compared with the ST8Sia IV mRNA. Competitive PCR analysis of the
      adult mouse CNS showed weak expression of the two genes in the olfactory bulb,
      thalamus, hippocampus, and eyes. The regional and transient expression of ST8Sia
      II mRNA coincides with that of PSA, suggesting that ST8Sia II is closely involved
      in the biosynthesis and expression of PSA in the developing mouse CNS.

PMID- 9231708
TI  - Apoptosis of retinal photoreceptors during development in vitro: protective
      effect of docosahexaenoic acid.
AB  - When rat retinal cells are cultured in a serum-free medium, the photoreceptor
      cells start dying after 7 days. The addition of docosahexaenoic acid (DHA) to the
      cultures prevents the selective death of photoreceptors. Here it is shown that,
      unlike other retinal neurons, photoreceptors die through an apoptotic pathway.
      Hallmarks of apoptosis, such as nuclear fragmentation and condensation and DNA
      cleavage forming a ladder pattern on an agarose gel, were observed. The timing
      and high selectivity of the triggering of photoreceptor cell apoptosis suggest
      the existence of a programmed cell death. Compared with other fatty acids, DHA
      not only was the most effective in promoting photoreceptor survival, but also the
      only one to decrease the number of apoptotic nuclei. The results suggest that DHA
      is important among the factors preventing apoptosis of photoreceptors in the
      developing retina. A limitation in the availability of this fatty acid might
      trigger apoptosis as a result of the failure to develop functional photoreceptor
      outer segments.

PMID- 9231709
TI  - BCL-2-related protein expression in apoptosis: oxidative stress versus serum
      deprivation in PC12 cells.
AB  - Expression of the BCL-2 protein family members, BAX, BAK, BAD, BCL-xL, BCL-xS,
      and BCL-2, was measured (by western blotting using specific antibodies) in PC12
      cells before and during apoptosis induced by either H2O2 treatment or by serum
      deprivation and during rescue from apoptosis by nerve growth factor (NGF). H2O2
      induced apoptosis, as measured by DNA fragmentation, caused: (a) a dose-dependent
      increase in BAX, (b) a dose-independent increase in BAK, and (c) a dose-dependent
      inhibition of BAD expression. By comparison, apoptosis induced by serum
      deprivation resulted in a time-dependent decrease in both BAX and BAK, along with
      a dramatic and sudden decrease in BAD expression. However, when PC12 cells were
      incubated in an apoptosis-sparing medium (i.e., NGF-supplemented serum-free
      medium), both BAX and BAK were increased significantly, whereas BAD expression
      remained inhibited. BCL-xL expression was increased by H2O2 but unaffected by
      serum deprivation or long-term NGF treatment. Neither BCL-2 nor BCL-xS expression
      could be detected in PC12 cells under the experimental conditions tested. Our
      results show that the expression of BAX, BAK, BAD, and BCL-xL is altered in a
      stimulus-dependent manner but cannot be used to define whether a cell will
      undergo or survive apoptosis. The similarity between changes in expression of BCL
      2-related proteins induced by H2O2 exposure and NGF rescue could reflect
      activation in part of a common antioxidant pathway.

PMID- 9231710
TI  - Mitochondrial permeability transition in the central nervous system: induction by
      calcium cycling-dependent and -independent pathways.
AB  - Isolated rat CNS mitochondria and cultured cortical astrocytes were examined for
      behavior indicative of a mitochondrial permeability transition (mPT). Exposure of
      isolated CNS mitochondria to elevated calcium or phosphate or both produced loss
      of absorbance indicative of mitochondrial swelling. The absorbance decreases were
      prevented by ADP and Mg2+ and reduced by cyclosporin A, dithiothreitol, and N
      ethylmaleimide. Ruthenium red prevented calcium cycling-induced, but only
      attenuated phosphate-induced losses of absorbance. In cultured astrocytes
      permeabilized with digitonin or treated with the calcium ionophore, 4-bromo
      A23187, elevations of external calcium altered mitochondrial morphology
      visualized with the dye, JC-1, from rod-like to rounded, swollen structures.
      Similar changes were observed in digitonin-permeabilized astrocytes exposed to
      phosphate. The incidence of calcium-induced changes in astrocyte mitochondria was
      prevented by Mg2+ and pretreatment with dithiothreitol and N-ethylmaleimide, and
      was reduced by cyclosporin A, ADP, and butacaine alone or in combinations.
      Ruthenium red and the Na+/Ca2+ exchange inhibitor CGP 37157 blocked calcium
      cycling and prevented mitochondrial shape changes in digitonin-treated, but not
      ionophore-treated astrocytes. Thus, the demonstrated induction conditions and
      pharmacological profile indicated the existence of an mPT in brain mitochondria.
      The mPT occurred consequent to activation of calcium cycling-dependent and 
      independent pathways. Induction of an mPT could contribute to neuronal injury
      following ischemia and reperfusion.

PMID- 9231711
TI  - Two waves of cyclin B and proliferating cell nuclear antigen expression during
      dopamine-triggered neuronal apoptosis.
AB  - The neurotransmitter dopamine is capable of inducing apoptosis in postmitotic
      sympathetic neurons via its oxidative metabolites. To detect genes whose
      expression is transcriptionally regulated during the early stages of dopamine
      triggered apoptosis, we applied the differential display method to cultured
      sympathetic neurons. One of the up-regulated genes was identified as cyclin B2,
      which exhibited two waves of induction and destruction, both at the mRNA and
      protein levels, resembling the sequential oscillations typical of two successive
      mitotic events in proliferating cells. The time window between the two waves was
      characterized by a change in expression of other cell-cycle stage-specific genes,
      and oscillations in proliferating cell nuclear antigen and alterations in cyclin
      A were observed. Cyclin D1 and cyclin-dependent kinases were undetected and no
      sign of active DNA synthesis could be observed, indicating that activation of
      cell-cycle components is incomplete. In comparison with a normal cell cycle,
      temporal expression profile of these mediators was unsynchronized. Whereas the
      first wave of cell-cycle changes occurred prior to the commitment of the cells to
      the death process and could be tolerated by the cells, the second wave of changes
      coincided with the death commitment point. Our findings indicate that
      inappropriate and incomplete activation of some cell cycle-related genes in
      postmitotic neurons occurs during dopamine-triggered neuronal apoptosis.

PMID- 9231712
TI  - Comparison between the timing of JNK activation, c-Jun phosphorylation, and onset
      of death commitment in sympathetic neurones.
AB  - We have investigated the relationship between c-Jun N-terminal kinase (JNK)
      activity, apoptosis, and the potential of survival factors to rescue primary rat
      sympathetic neurones deprived of trophic support. Incubation of sympathetic
      neurones in the absence of nerve growth factor (NGF) caused a time-dependent
      increase in JNK activity, which became apparent by 3 h and attained maximal
      levels that were three- to fourfold higher than activity measured in neurones
      maintained for the same periods with NGF. Continuous culture in the presence of
      either NGF or the cyclic AMP analogue 4-(8-chlorophenylthio) cyclic AMP (CPTcAMP)
      not only prevented JNK activation from occurring, but also suppressed JNK
      activity that had been elevated by prior culture of the neurones in the absence
      of trophic support. When either NGF or CPTcAMP was added to cultures that had
      been initially deprived of neurotrophic support for up to 10 h, this resulted in
      complete suppression of total JNK activity, arrest of apoptosis, and rescue of
      >90% of the neurones that did not display apoptotic morphology by this time.
      However, when either agent was added after more protracted periods of initial
      neurotrophin deprivation (> or = 14 h), although this also resulted in near
      complete suppression of total JNK activity and short-term arrest of apoptosis,
      not all of the neurones that appeared to be nonapoptotic at the time of agent
      addition were rescued. The lack of death commitment after 10 h of maintained JNK
      activity was not due to a late induction of c-Jun expression, because the
      majority of newly isolated sympathetic neurones had already been expressing high
      levels of c-Jun in their nuclei for several hours, yet were capable of being
      rescued by NGF. Elevation of JNK activity as a result of neurotrophic-factor
      deprivation was also associated with enhanced phosphorylation of c-Jun, assessed
      by immunoblot analysis and immunocytochemistry, and addition of NGF to cultures
      previously deprived of neurotrophic support resulted in a reversion of the state
      of phospho-c-Jun to that observed in cultures that had been maintained in the
      continuous presence of trophic support. We conclude that activation of JNK and c
      Jun phosphorylation are not necessarily rate-limiting for apoptosis induction. In
      some neurones undergoing prolonged NGF deprivation, suppression of JNK activity
      and c-Jun dephosphorylation by NGF may be insufficient to effect their rescue.
      Thus, if c-Jun mediates death by increasing the expression of "death" genes,
      these must become effective very close to the death commitment point.

PMID- 9231713
TI  - Microtubule dynamics regulates the level of endothelin-B receptor in rat cultured
      astrocytes.
AB  - We investigated the effect of cytoskeleton modulators on endothelin-B (ET(B))
      receptor expression in rat primary cultured astrocytes. Northern blot analysis
      and a binding study revealed that colchicine and nocodazole, microtubule
      disrupting agents, decreased the levels of both ET(B) receptor mRNA and the
      number of ET-1 binding sites in quiescent astrocytes. Down-regulation of both
      ET(B) receptor mRNA and the number of binding sites for ET-1 was also observed in
      quiescent astrocytes treated with taxol, a microtubule-stabilizing agent. In
      contrast, neither beta-lumicolchicine, an inactive isomer of colchicine, nor
      cytochalasin D, a microfilament-disrupting agent, influenced ET(B) receptor
      expression. The level of ET(B) receptors in astrocytes was affected by the cell
      state, namely, proliferative, quiescent, or differentiated state. The order of
      ET(B) receptor expression according to the cell state was proliferative state <
      quiescent state << differentiated state induced by dibutyryl cyclic AMP. Also, in
      proliferative astrocytes and differentiated astrocytes, colchicine significantly
      down-regulated both ET(B) receptor mRNA and the number of binding sites for ET-1.
      However, thymidine assay revealed that colchicine did not change quiescent
      astrocytes and differentiated astrocytes to a proliferative state. Furthermore,
      the increase in glutamine synthetase activity in differentiated astrocytes was
      not affected by colchicine. These results suggest that microtubule dynamics
      possibly regulates ET(B) receptor expression in astrocytes without affecting the
      cell state.

PMID- 9231715
TI  - Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) reduction.
AB  - 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction is
      one of the most frequently used methods for measuring cell proliferation and
      neural cytotoxicity. It is widely assumed that MTT is reduced by active
      mitochondria in living cells. By using isolated mitochondria from rat brain and
      B12 cells, we indeed found that malate, glutamate, and succinate support MTT
      reduction by isolated mitochondria. However, the data presented in this study do
      not support the exclusive role of mitochondria in MTT reduction by intact cells.
      Using a variety of approaches, we found that MTT reduction by B12 cells is
      confined to intracellular vesicles that later give rise to the needle-like MTT
      formazan at the cell surface. Some of these vesicles were identified as endosomes
      or lysosomes. In addition, MTT was found to be membrane impermeable. These and
      other results suggest that MTT is taken up by cells through endocytosis and that
      reduced MTT formazan accumulates in the endosomal/lysosomal compartment and is
      then transported to the cell surface through exocytosis.

PMID- 9231714
TI  - 4-Hydroxynonenal, an aldehydic product of lipid peroxidation, impairs signal
      transduction associated with muscarinic acetylcholine and metabotropic glutamate
      receptors: possible action on G alpha(q/11).
AB  - Considerable data indicate that oxidative stress and membrane lipid peroxidation
      contribute to neuronal degeneration in an array of age-related neurodegenerative
      disorders. In contrast, the impact of subtoxic levels of membrane lipid
      peroxidation on neuronal function is largely unknown. We now report that 4
      hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, disrupts
      coupling of muscarinic cholinergic receptors and metabotropic glutamate receptors
      to phospholipase C-linked GTP-binding proteins in cultured rat cerebrocortical
      neurons. At subtoxic concentrations, HNE markedly inhibited GTPase activity,
      inositol phosphate release, and elevation of intracellular calcium levels induced
      by carbachol (muscarinic agonist) and (RS)-3,5-dihydroxyphenyl glycine
      (metabotropic glutamate receptor agonist). Maximal impairment of agonist-induced
      responses occurred within 30 min of exposure to HNE. Other aldehydes, including
      malondialdehyde, had little effect on agonist-induced responses. Antioxidants
      that suppress lipid peroxidation did not prevent impairment of agonist-induced
      responses by HNE, whereas glutathione, which is known to bind and detoxify HNE,
      did prevent impairment of agonist-induced responses. HNE itself did not induce
      oxidative stress. Immunoprecipitation-western blot analysis using an antibody to
      HNE-protein conjugates showed that HNE can bind to G alpha(q/11). HNE also
      significantly suppressed inositol phosphate release induced by aluminum fluoride.
      Collectively, our data suggest that HNE plays a role in altering receptor-G
      protein coupling in neurons under conditions of oxidative stress that may occur
      both normally, and before cell degeneration and death in pathological settings.

PMID- 9231716
TI  - Extracellular calcium sensing by glial cells: low extracellular calcium induces
      intracellular calcium release and intercellular signaling.
AB  - Glial cells in primary mixed cultures or purified astrocyte cultures from mouse
      cortex respond to reduced extracellular calcium concentration ([Ca2+]e) with
      increases in intracellular calcium concentration ([Ca2+]i) that include single
      cell Ca2+ oscillations and propagated intercellular Ca2+ waves. The rate and
      pattern of propagation of low [Ca2+]e-induced intercellular Ca2+ waves are
      altered by rapid perfusion of the extracellular medium, suggesting the
      involvement of an extracellular messenger in Ca2+ wave propagation. The low
      [Ca2+]e-induced Ca2+ response is abolished by thapsigargin and by the
      phospholipase antagonist U73122. The low [Ca2+]e-induced response is also blocked
      by replacement of extracellular Ca2+ with Ba2+, Zn2+, or Ni2+, and by 100 microM
      La3+. Glial cells in lowered [Ca2+]e (0.1-0.5 mM) show an increased [Ca2+]i
      response to bath application of ATP, whereas glial cells in increased [Ca2+]e (10
      15 mM) show a decreased [Ca2+]i response to ATP. These results show that glial
      cells possess a mechanism for coupling between [Ca2+]e and the release of Ca2+
      from intracellular stores. This mechanism may be involved in glial responses to
      the extracellular environment and may be important in pathological conditions
      associated with low extracellular Ca2+ such as seizures or ischemia.

PMID- 9231717
TI  - Selective changes in cell bodies and growth cones of nerve growth factor
      differentiated PC12 cells induced by chemical hypoxia.
AB  - Cytosolic free Ca2+ concentration ([Ca2+]i) was measured in differentiated PC12
      cells to test whether chemical hypoxia selectively alters intracellular Ca2+ in
      growth cones and cell bodies. Hypoxia increased [Ca2+]i and exaggerated its
      response to K+ depolarization in both parts of the cells. [Ca2+]i in the cell
      bodies was greater than that in the growth cones under resting conditions and in
      response to K+ or hypoxia. Ca2+-channel blockers selectively altered these
      responses. The L-channel blocker nifedipine reduced [Ca2+]i following K+
      depolarization by 67% in the cell bodies but only 25% in the growth cones. In
      contrast, the N-channel blocker omega-conotoxin GVIA (omega-CgTX) diminished K+
      induced changes in [Ca2+]i only in the growth cones. During hypoxia, nifedipine
      was more effective in the cell bodies than in the growth cones. During hypoxia,
      omega-CgTX diminished K+-induced changes by 50-75% in both parts of the cell, but
      only immediately after depolarization. The combination of nifedipine and omega
      CgTX diminished the [Ca2+]i response to K+ with or without hypoxia by >90% in the
      cell body and 70% in the growth cones. Thus, the increased Ca2+ entry with K+
      during hypoxia is primarily through L channels in the cell bodies, whereas in
      growth cones influx through L and N channels is about equal. The results show
      that chemical hypoxia selectively alters Ca2+ regulation in the growth cone and
      cell body of the same cell.

PMID- 9231718
TI  - Regulation of astrocyte nitric oxide synthase type II expression by ATP and
      glutamate involves loss of transcription factor binding to DNA.
AB  - Pretreatment of astrocytes with either glutamate or ATP, acting via specific
      receptors, suppresses subsequent cytokine-induced expression of type II nitric
      oxide synthase (NOS). This effect is downstream from the activation and
      translocation of nuclear factor (NF)-kappaB, as western blotting revealed no
      difference in accumulation of the p50 subunit in nuclear extracts from agonist
      treated vs. nontreated cells. However, evidence from gel-shift assay suggests
      that the binding of nuclear protein from agonist-treated cells to NF-kappaB and
      activator protein-1 consensus oligonucleotides is markedly reduced. Selective
      inhibitors of protein kinases A and C could not restore either binding of
      transcription factors to DNA or type II NOS mRNA expression in agonist-pretreated
      cells. The modulation of proinflammatory cytokine-evoked type II NOS expression
      by ATP and glutamate may play an important role in CNS pathologies associated
      with stroke and trauma.

PMID- 9231719
TI  - Apoptosis induced via AMPA-selective glutamate receptors in cultured murine
      cortical neurons.
AB  - We have investigated the mechanisms of cell death induced by long-term exposure
      to the glutamate receptor agonist (S)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate [(S)-AMPA]. Using primary cultures of pure neurons (95%)
      grown in serum-free conditions, we found that 24-h exposure to (S)-AMPA (0.01
      1,000 microM) induced concentration-dependent neuronal cell death (EC50 = 3 +/-
      0.5 microM) with cellular changes including neurite blebbing, chromatin
      condensation, and DNA fragmentation, indicative of apoptosis. (S)-AMPA induced a
      delayed cell death with DNA fragmentation occurring in approximately 50% of cells
      at concentrations between 100 and 300 microM detected using terminal transferase
      mediated dUTP nick end-labeling (TUNEL) and agarose gel electrophoresis.
      Apoptotic chromatin condensation was detected using 4,6-diamidino-2-phenylindole,
      a fluorescent DNA binding dye. Cell death induced by (S)-AMPA was attenuated by
      the AMPA receptor-selective antagonist LY293558 (10 microM) and the non-NMDA
      receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM),
      yielding EC50 values of 73 +/- 5 and 265 +/- 8 microM, respectively, and was
      unaffected by the NMDA receptor antagonist MK-801 (10 microM). The number of
      apoptotic nuclei induced by 300 microM (S)-AMPA (57%) was also reduced
      substantially by the antagonists LY293558 and CNQX, with only 20% and 18% of
      neurons, respectively, staining TUNEL-positive at 24 h. In addition,
      cycloheximide (0.5 microg/ml) also inhibited (S)-AMPA-induced DNA fragmentation
      and cell death. Our results show that long-term exposure to AMPA can induce
      substantial neuronal death involving apoptosis in cultured cortical neurons,
      suggesting a wide involvement of AMPA-sensitive glutamate receptors in
      excitotoxic injury and neurodegenerative pathologies.

PMID- 9231720
TI  - The N-methyl-D-aspartate receptor subunits NR2A and NR2B bind to the SH2 domains
      of phospholipase C-gamma.
AB  - The NMDA receptor has recently been found to be phosphorylated on tyrosine. To
      assess the possible connection between tyrosine phosphorylation of the NMDA
      receptor and signaling pathways in the postsynaptic cell, we have investigated
      the relationship between tyrosine phosphorylation and the binding of NMDA
      receptor subunits to the SH2 domains of phospholipase C-gamma (PLC-gamma). A
      glutathione S-transferase (GST) fusion protein containing both the N- and the C
      proximal SH2 domains of PLC-gamma was bound to glutathione-agarose and reacted
      with synaptic junctional proteins and glycoproteins. Tyrosine-phosphorylated PSD
      GP180, which has been identified as the NR2B subunit of the NMDA receptor, bound
      to the SH2-agarose beads in a phosphorylation-dependent fashion. Immunoblot
      analysis with antibodies specific for individual NMDA receptor subunits showed
      that both NR2A and NR2B subunits bound to the SH2-agarose. No binding occurred to
      GST-agarose lacking an associated SH2 domain, indicating that binding was
      specific for the SH2 domains. The binding of receptor subunits increased after
      the incubation of synaptic junctions with ATP and decreased after treatment of
      synaptic junctions with exogenous protein tyrosine phosphatase.
      Immunoprecipitation experiments confirmed that NR2A and NR2B were phosphorylated
      on tyrosine and further that tyrosine phosphorylation of each of the subunits was
      increased after incubation with ATP. The results demonstrate that NMDA receptor
      subunits NR2A and NR2B will bind to the SH2 domains of PLC-gamma and that
      isolated synaptic junctions contain endogenous protein tyrosine kinase(s) that
      can phosphorylate both NR2A and NR2B receptor subunits, and suggest that
      interaction of the tyrosine-phosphorylated NMDA receptor with proteins that
      contain SH2 domains may serve to link it to signaling pathways in the
      postsynaptic cell.

PMID- 9231721
TI  - Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule
      cells occurs via facilitated diffusion.
AB  - N-Arachidonoylethanolamine (anandamide, AEA) is a putative endogenous ligand of
      the cannabinoid receptor. Intact cerebellar granule neurons in primary culture
      rapidly accumulate AEA. [3H]AEA accumulation by cerebellar granule cells is
      dependent on incubation time (t(1/2) of 2.6 +/- 0.8 min at 37 degrees C) and
      temperature. The accumulation of AEA is saturable and has an apparent Km of 41 +/
      15 microM and a Vmax of 0.61 +/- 0.04 nmol/min/10(6) cells. [3H]AEA accumulation
      by cerebellar granule cells is significantly reduced by 200 microM phloretin
      (57.4 +/- 4% of control) in a noncompetitive manner. [3H]AEA accumulation is not
      inhibited by either ouabain or removal of extracellular sodium. [3H]AEA
      accumulation is fairly selective for AEA among other naturally occurring N
      acylethanolamines; only N-oleoylethanolamine significantly inhibited [3H]AEA
      accumulation at a concentration of 10 microM. The ethanolamides of palmitic acid
      and linolenic acid were inactive at 10 microM. N-Arachidonoylbenzylamine and N
      arachidonoylpropylamine, but not arachidonic acid, 15-hydroxy-AEA, or 12-hydroxy
      AEA, compete for AEA accumulation. When cells are preloaded with [3H]AEA,
      temperature-dependent efflux occurs with a half-life of 1.9 +/- 1.0 min.
      Phloretin does not inhibit [3H]AEA efflux from cells. These results suggest that
      AEA is accumulated by cerebellar granule cells by a protein-mediated transport
      process that has the characteristics of facilitated diffusion.

PMID- 9231722
TI  - Comparison of [3H]phosphatidylinositol and [3H]phosphatidylinositol 4,5
      bisphosphate hydrolysis in postmortem human brain membranes and characterization
      of stimulation by dopamine D1 receptors.
AB  - Assessing the function of the phosphoinositide signal transduction system in
      membranes prepared from postmortem human brain by measuring the hydrolysis of
      exogenous labeled phosphoinositides has been applied to studies of a variety of
      CNS disorders in recent years. Two issues concerning such studies were addressed
      in the current investigation: how do [3H]phosphatidylinositol and
      [3H]phosphatidylinositol 4,5-bisphosphate compare as substrates, and how do
      dopamine D1 receptors influence phosphoinositide signaling? Comparisons of
      [3H]phosphatidylinositol and [3H] phosphatidylinositol 4,5-bisphosphate
      hydrolysis stimulated by guanosine-5'-O-(3-thiotriphosphate)-activated G proteins
      and by several receptor agonists demonstrated that in most cases each substrate
      gave similar relative results in membranes prepared from prefrontal cortices of
      six individuals. However, using optimal assay conditions,
      [3H]phosphatidylinositol produced a greater signal-to-noise ratio compared with
      [3H] phosphatidylinositol 4,5-bisphosphate. Dopamine D1 receptors were
      demonstrated to be directly coupled to phosphoinositide hydrolysis in human brain
      membranes, and this response was shown to be mediated by the G(q/11) G protein
      subtype and by the beta-subtype of phospholipase C. Therefore, these results
      demonstrate that [3H]phosphatidylinositol is a suitable substrate to measure
      phosphoinositide hydrolysis in human brain membranes and that dopamine D1
      receptors directly stimulate this signaling system.

PMID- 9231723
TI  - Dopaminergic properties of cultured rat carotid body chemoreceptors grown in
      normoxic and hypoxic environments.
AB  - Using dissociated carotid body (CB) cultures prepared from neonatal (postnatal
      days 5-7; P7) or juvenile (postnatal day 19-20; P20) rats, we compared
      catecholaminergic properties and mechanisms of O2 sensing in glomus cells grown
      in normoxic (Nox; 20% O2) and chronically hypoxic (CHox; 6% O2) environments for
      up to 2 weeks. In Nox cultures, basal dopamine (DA) release, determined by HPLC
      and normalized to the number of tyrosine hydroxylase-positive glomus cells
      present, was similar for P7 and P20 cultures (approximately 0.3 pmol/1,000
      cells/15 min) and was unaffected by culture duration (2 vs. 12 days). Acute
      hypoxia (5 and 10% O2) caused a dose-dependent stimulation (6x and 3x basal,
      respectively) in DA release, that was inhibited by nifedipine (10 microM). DA
      release was also stimulated by high extracellular K+ (30 mM) and iberiotoxin (200
      nM), a selective blocker of PO2-regulated, Ca-dependent K+ channel in glomus
      cells. The stimulatory effect of iberiotoxin was similar to 5% O2 in P20
      cultures, but substantially less (about one-half) in P7 cultures. In contrast, in
      CHox cultures, basal DA release was substantially elevated, approximately 8x Nox
      levels, although this did not correlate with significant differences in stores.
      Further, whereas acute hypoxia (5% O2) and high K+ also stimulated DA release in
      CHox cultures (approximately 2x and approximately 3x basal), iberiotoxin (200 nM)
      did not. Thus, after chronic hypoxia in vitro, there is an enhanced basal
      catecholamine release and an apparent down-regulation of functional Ca-dependent
      K+ channels in CB chemoreceptors. These cellular adaptations may relate to
      changes in CB chemosensitivity during chronic hypoxemia.

PMID- 9231724
TI  - Brain tissue acidosis: effects on the extracellular concentration of N
      acetylaspartate.
AB  - N-Acetylaspartate (NAA) is characterized by a high tissue-to-extracellular
      concentration ratio under normal conditions and is released from neurons during
      hypoosmotic cell swelling. As cell volume regulation and acid-base homeostasis
      share common processes, we have examined by microdialysis whether the
      extracellular concentration of NAA is altered by various acidotic challenges.
      Twenty-minute perfusion of 50 mM NH4+ through the microdialysis probe
      progressively lowered dialysate pH by 0.18, followed by a sudden, additional
      reduction after NH4+ removal. The latter effect indicated extrusion of cellular
      H+ because it was suppressed by blockade of Na+/H+ exchange with 5-(N,N
      dimethyl)amiloride (1 or 5 mM in perfusion medium). NH4+ increased dialysate
      levels of NAA and lactate by approximately two- and threefold their initial
      values, respectively. These data demonstrate that pronounced intracellular
      acidosis is associated with NAA efflux, presumably from neurons. Whether this
      effect is linked directly to acid-base homeostasis or is secondary to acidosis
      induced cell swelling remains to be clarified. Hypercapnia and perfusion of acid
      medium failed to increase dialysate NAA, probably because acidosis was not severe
      enough or the associated cellular swelling was not followed by regulatory volume
      decrease. As cellular swelling and acidosis are key features of cerebral
      ischaemia, further investigations into the role of NAA, and the development of
      sophisticated magnetic resonance spectroscopic methods capable of resolving intra
      /extracellular NAA redistribution, would be especially relevant to clinical
      practice.

PMID- 9231725
TI  - Eating-induced dopamine release from mesolimbic neurons is mediated by NMDA
      receptors in the ventral tegmental area: a dual-probe microdialysis study.
AB  - This study was aimed at identifying the neuronal pathways that mediate the eating
      induced increase in the release of dopamine in the nucleus accumbens of the rat
      brain. For that purpose, a microdialysis probe was implanted in the ventral
      tegmental area and a second probe was placed in the ipsilateral nucleus
      accumbens. Receptor-specific compounds acting on GABA(A) (40 microM muscimol; 50
      microM bicuculline), GABA(B) (50 microM baclofen), acetylcholine (50 microM
      carbachol), NMDA [30 microM (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic
      acid (CPP)], and non-NMDA [300 microM 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX)] receptors were infused into the ventral tegmental area by retrograde
      dialysis, whereas extracellular dopamine was recorded in the ipsilateral nucleus
      accumbens. Intrategmental infusion of muscimol or baclofen decreased
      extracellular dopamine in the ipsilateral nucleus accumbens; CPP and CNQX were
      without effect, and bicuculline and carbachol increased dopamine release. During
      infusion of the various compounds, food-deprived rats were allowed to eat for 10
      min. The infusions of muscimol, bicuculline, baclofen, carbachol, and CNQX did
      not prevent the eating-induced increase in extracellular dopamine in the nucleus
      accumbens. However, during intrategmental infusion of CPP, the eating-induced
      increase in extracellular dopamine in the nucleus accumbens was suppressed. These
      results indicate that a glutamatergic projection to the ventral tegmental area
      mediates, via an NMDA receptor, the eating-induced increase in dopamine release
      from mesolimbic dopamine neurons.

PMID- 9231726
TI  - Inhibition of inducible nitric oxide synthase expression by endothelin in rat
      glial cells prepared from the neonatal rat brain.
AB  - In primary cultured rat glial cells, a combination of inflammatory cytokines such
      as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)
      stimulates production of nitrite via expression of the inducible form of nitric
      oxide synthase (iNOS). In these cells, simultaneous addition of endothelin (ET)
      decreased iNOS expression and nitrite accumulation induced by TNF-alpha/IL-1beta.
      The inhibitory effect of ET on TNF-alpha/IL-1beta-stimulated iNOS expression
      appears to be mediated by ET(B) receptors, because (1) both ET-1 and ET-3
      inhibited the effects of TNF-alpha/IL-1beta on iNOS expression and nitrite
      accumulation, (2) a selective ET(B) receptor agonist, Suc-[Glu(9),Ala(11,15)]-ET
      1 (8-21) (IRL1620), decreased the effects of TNF-alpha/IL-1beta, and (3) a
      selective ET(B) receptor antagonist, N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma
      methylleucyl-D- 1-methoxycarbonyltryptophanyl-D-norleucine, abolished the
      inhibitory effects of ETs and IRL1620. Incubation of glial cells with
      lipopolysaccharide (LPS) caused an increase in iNOS expression. Simultaneous
      addition of ET-3 decreased the effects of LPS (10 and 100 ng/ml) on iNOS
      expression. Furthermore, cyclic AMP-elevating agents (dibutyryl cyclic AMP and
      forskolin) inhibited TNF-alpha/IL-1beta-induced and LPS-induced iNOS expression
      and nitrite accumulation. These findings suggest that ETs can decrease TNF
      alpha/IL-1beta-induced and LPS-induced iNOS expression via ET(B) receptors and
      that cyclic AMP may be involved in this process.

PMID- 9231727
TI  - Normal binding and reactivity of copper in mutant superoxide dismutase isolated
      from amyotrophic lateral sclerosis patients.
AB  - In some families with amyotrophic lateral sclerosis (ALS), the disease is linked
      to mutations in the gene encoding CuZn-superoxide dismutase. The mutant CuZn
      superoxide dismutases appear to cause motor neuron degeneration by a toxic
      property, suggested to be linked to an altered reactivity of the active-site Cu
      ions. Asp90Ala mutant CuZn-superoxide dismutase was isolated from six patients
      with ALS, allowing properties of the mutant enzyme synthesized and conditioned in
      patients with ALS to be examined. The molecular mass of the Asp90Ala mutant CuZn
      superoxide dismutase was 45 Da lower than that of the wild-type enzyme, as
      expected from the amino acid exchange. The mobility after sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was markedly increased, however, suggesting
      altered properties of the polypeptide. The mutant CuZn-superoxide dismutase
      showed a minimal reduction in stability but did not differ significantly from the
      wild-type enzyme in enzymic activity, in content and affinity for active-site Cu
      ions and in the propensity to catalyze formation of hydroxyl radicals. Our
      findings suggest that the deleterious effect of mutant CuZn-superoxide dismutases
      on motor neurons in ALS is not related to altered reactivity of active-site Cu
      ions, resulting in increased oxidant stress. Attention should therefore also be
      directed at other mechanisms and properties of the mutant polypeptides and their
      degradation products.

PMID- 9231728
TI  - Effects of ketone bodies on astrocyte amino acid metabolism.
AB  - The effects of acetoacetate and 3-hydroxybutyrate on glial amino acid metabolism
      were studied in primary cultures of astrocytes. The exchange of nitrogen among
      amino acids was measured with 15N as a metabolic probe and gas chromatography
      mass spectrometry as a tool with which to quantify isotope abundance. Addition of
      either acetoacetate or 3-hydroxybutyrate (5 mM) to the incubation medium did not
      alter the initial rate of appearance of [15N]glutamate in the glia, but it did
      inhibit transamination of glutamate to [15N]aspartate. Addition of acetoacetate
      also inhibited formation of [2-(15)N]glutamine, but 3-hydroxybutyrate had a
      stimulatory effect. The presence in the medium of sodium acetate (5 mM) was also
      associated with diminished production of [15N]aspartate and [2-(15)N]glutamine
      with [15N]glutamate as precursor. Studies with [2-(15)N]glutamine as precursor
      indicated that treatment of the astrocytes with ketone bodies did not alter flux
      through the glutaminase pathway. Nor did the presence of the ketone bodies reduce
      significantly the flux of nitrogen from [15N]GABA to [2-(15)N]glutamine when the
      former species served as a metabolic tracer. The concentration of internal
      citrate increased in the presence of acetoacetate, 3-hydroxybutyrate, and
      acetate. Studies with purified sheep brain glutamine synthetase showed that
      citrate inhibited this enzyme. These findings are considered in terms of the
      known anticonvulsant effect of a ketogenic diet.

PMID- 9231729
TI  - Domoic acid neurotoxicity in cultured cerebellar granule neurons is mediated
      predominantly by NMDA receptors that are activated as a consequence of excitatory
      amino acid release.
AB  - The participation of NMDA and non-NMDA receptors in domoic acid-induced
      neurotoxicity was investigated in cultured rat cerebellar granule cells (CGCs).
      Neurons were exposed to 300 microM L-glutamate or 10 microM domoate for 2 h in
      physiologic buffer at 22 degrees C followed by a 22-h incubation in 37 degrees C
      conditioned growth media. Excitotoxic injury was monitored as a function of time
      by measurement of lactate dehydrogenase (LDH) activity in both the exposure
      buffer and the conditioned media. Glutamate and domoate evoked, respectively, 50
      and 65% of the total 24-h increment in LDH efflux after 2 h. Hyperosmolar
      conditions prevented this early response but did not significantly alter the
      extent of neuronal injury observed at 24 h. The competitive NMDA receptor
      antagonist D(-)-2-amino-5-phosphonopentanoic acid and the non-NMDA receptor
      antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) reduced
      glutamate-induced LDH efflux totals by 73 and 27%, respectively, whereas,
      together, these glutamate receptor antagonists completely prevented neuronal
      injury. Domoate toxicity was reduced 65-77% when CGCs were treated with
      competitive and noncompetitive NMDA receptor antagonists. Unlike the effect on
      glutamate toxicity, NBQX completely prevented domoate-mediated injury. HPLC
      analysis of the exposure buffer revealed that domoate stimulates the release of
      excitatory amino acids (EAAs) and adenosine from neurons. Domoate-stimulated EAA
      release occurred almost exclusively through mechanisms related to cell swelling
      and reversal of the glutamate transporter. Thus, whereas glutamate-induced injury
      is mediated primarily through NMDA receptors, the full extent of
      neurodegeneration is produced by the coactivation of both NMDA and non-NMDA
      receptors. Domoate-induced neuronal injury is also mediated primarily through
      NMDA receptors, which are activated secondarily as a consequence of alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor-mediated
      stimulation of EAA efflux.

PMID- 9231730
TI  - Metabotropic glutamate receptor subtype mGluR1alpha stimulates the secretion of
      the amyloid beta-protein precursor ectodomain.
AB  - To examine the effects of glutamatergic neurotransmission on amyloid processing,
      we stably expressed the metabotropic glutamate receptor subtype 1alpha (mGlu
      R1alpha) in HEK 293 cells. Both glutamate and the selective metabotropic agonist
      1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) rapidly increased
      phosphatidylinositol (PI) turnover four- to fivefold compared with control cells
      that were transfected with the expression vector alone. Increased PI turnover was
      effectively blocked by the metabotropic antagonist alpha-methyl-4
      carbophenylglycine (MCPG), indicating that heterologous expression of mGluR1alpha
      resulted in efficient coupling of the receptors to G protein and phospholipase C
      activation. Stimulation of mGluR1alpha with glutamate, quisqualate, or ACPD
      rapidly increased secretion of the APP ectodomain (APPs); these effects were
      blocked by MCPG. The metabotropic receptors were coupled to APP processing by
      protein kinases and by phospholipase A2 (PLA2), and melittin, a peptide that
      stimulates PLA2, potently increased APPs secretion. These data indicate that
      mGluR1alpha can be involved in the regulation of APP processing. Together with
      previous findings that muscarinic and serotonergic receptor subtypes can increase
      the secretion of the APP ectodomain, these observations support the concept that
      proteolytic processing of APP is under the control of several major
      neurotransmitters.

PMID- 9231731
TI  - Changes in the activity and mRNA levels of phospholipase D during ceramide
      induced apoptosis in rat C6 glial cells.
AB  - N-Acetylsphingosine (C2-ceramide), a membrane-permeable analogue, induced
      apoptosis in C6 glial cells. Phase-contrast micrographs showed that the round
      cells appeared 3 h after exposure to 25 microM C2-ceramide and the number of
      floating cells increased time-dependently. Staining with Hoechst 33258 dye showed
      condensed or fragmented nuclei in round cells at 12 h. DNA fragmentation was also
      observed by agarose gel electrophoresis at 12 h. To understand the mechanism
      underlying glial cell death induced by C2-ceramide treatment, changes in
      phospholipase D (PLD) activity in response to guanosine 5'-O-(3-thiotriphosphate)
      (GTPgammaS) and expression of mRNA levels of PLD isozymes were examined. In cell
      lysate, GTPgammaS-dependent PLD activity was down-regulated after ceramide
      treatment in a time-dependent manner. In the in vitro PLD assay, membrane
      associated PLD activation in response to recombinant ADP-ribosylation factor 1
      was greatly suppressed. Furthermore, levels of rPLD1a and rPLD1b mRNAs were found
      to be down-regulated, whereas the level of rPLD2 mRNA increased gradually,
      peaking at 3 h, followed by a slow decrease, as inferred by reverse transcription
      polymerase chain reaction. Decreases in GTPgammaS-dependent PLD activity were
      well correlated with those in rPLD1a and rPLD1b mRNAs levels. Taken together,
      these data suggest that levels of PLD enzymes might be decreased by ceramide
      treatment.

PMID- 9231732
TI  - Oleic acid inhibits gap junction permeability and increases glucose uptake in
      cultured rat astrocytes.
AB  - The role of oleic acid in the modulation of gap junction permeability was studied
      in cultured rat astrocytes by the scrape-loading/Lucifer yellow transfer
      technique. Incubation with oleic acid caused a dose-dependent inhibition of gap
      junction permeability by 79.5% at 50 microM, and no further inhibition was
      observed by increasing the oleic acid concentration to 100 microM. The oleic acid
      mediated inhibition of gap junction permeability was reversible and was prevented
      by bovine serum albumin. The potency of oleic acid-related compounds in
      inhibiting gap junction permeability was arachidonic acid > oleic acid > oleyl
      alcohol > palmitoleic acid > stearic acid > octanol > caprylic acid > palmitic
      acid > methyloleyl ester. Oleic acid and arachidonic acid, but not methyloleyl
      ester, increased glucose uptake by astrocytes. Neither oleic acid nor arachidonic
      acid increased glucose uptake in the poorly coupled glioma C6 cells. These
      results support that the inhibition of gap junction permeability is associated
      with the increase in glucose uptake. We suggest that oleic acid may be a
      physiological mediator of the transduction pathway leading to the inhibition of
      intercellular communication.

PMID- 9231733
TI  - Hydrogen peroxide-induced phospholipase D activation in rat pheochromocytoma PC12
      cells: possible involvement of Ca2+-dependent protein tyrosine kinase.
AB  - The mechanism for hydrogen peroxide (H2O2)-induced phospholipase D (PLD)
      activation was investigated in [3H]palmitic acid-labeled PC12 cells. In the
      presence of butanol, H2O2 caused a great accumulation of [3H]phosphatidylbutanol
      in a concentration- or time-dependent manner. However, treatment with H2O2 of
      cell lysates exerted no effect on PLD activity. Treatment with H2O2 had only a
      marginal effect on phospholipase C (PLC) activation. A protein kinase C (PKC)
      inhibitor, Ro 31-8220, did not inhibit but rather slightly enhanced H2O2-induced
      PLD activity. Thus, H2O2-induced PLD activation is considered to be independent
      of the PLC-PKC pathway in PC12 cells. In contrast, pretreatment with tyrosine
      kinase inhibitor herbimycin A, genistein, or ST638 resulted in a concentration
      dependent inhibition of H2O2-induced PLD activation. Western blot analysis
      revealed several apparent tyrosine-phosphorylated protein bands after the H2O2
      treatment and tyrosine phosphorylation of these proteins was inhibited by these
      tyrosine kinase inhibitors. Moreover, depletion of extracellular Ca2+ abolished
      H2O2-induced PLD activation and protein tyrosine phosphorylation. Extracellular
      Ca2+ potentiated H2O2-induced PLD activation in a concentration-dependent manner.
      Taken together, these results suggest that a certain Ca2+-dependent protein
      tyrosine kinase(s) somehow participates in H2O2-induced PLD activation in PC12
      cells.

PMID- 9231734
TI  - Phosphorylation of neurofilament heavy-chain side-arm fragments by cyclin
      dependent kinase-5 and glycogen synthase kinase-3alpha in transfected cells.
AB  - The side-arm domain of neurofilament heavy-chain (NF-H) is heavily phosphorylated
      in axons. Much of this phosphate is located within a multiphosphorylation repeat
      (MPR) domain situated toward the carboxy terminus of the molecule. The MPR domain
      contains the repeat motif KSP of which there are two broad categories, KSPXX and
      KSPXK. In mouse NF-H, the KSPXK repeats are situated toward the latter part of
      the MPR domain. We have expressed in mammalian cells fragments of mouse NF-H side
      arm containing all of the MPR domain, the latter part of the MPR domain
      containing the KSPXK repeats, and the complementary amino-terminal part of the
      MPR domain, which contains the KSPXX repeats. By cotransfecting these fragments
      with the neurofilament kinases cyclin-dependent kinase-5 (cdk-5)/p35 and glycogen
      synthase kinase-3alpha (GSK-3alpha), we show that cdk-5 induces cellular
      phosphorylation of the KSPXK-containing fragment of NF-H. Using the transfected
      fragments, we also map the epitopes for several commonly utilised NF-H monoclonal
      antibodies and describe the effects that phosphorylation by cdk-5 and GSK-3alpha
      have on their reactivities.

PMID- 9231735
TI  - Inhibition of [3H]MK-801 binding by ferrous (II) but not ferric (III) ions in a
      manner different from that by sodium nitroprusside (II) in rat brain synaptic
      membranes.
AB  - The addition of sodium nitroprusside (SNP) significantly inhibited binding of (+)
      5- [3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) to
      an ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in a
      concentration-dependent manner at concentrations of >1 microM in rat brain
      synaptic membranes not extensively washed. However, neither S-nitroso-N
      acetylpenicillamine nor S-nitroso-L-glutathione inhibited binding even at 100
      microM. Of the two compounds structurally related to SNP (II), similarly potent
      inhibition was induced by potassium ferrocyanide (II) but not by potassium
      ferricyanide (III). In addition, ferrous chloride (II) induced much more potent
      inhibition of binding than ferric chloride (III), at a similar concentration
      range. In contrast, iron chelators prevented the inhibition by ferrous chloride
      (II) without markedly affecting that by SNP (II) and potassium ferrocyanide (II).
      Pretreatment with ferrous chloride (II) also led to potent inhibition of [3H]MK
      801 binding in a manner insensitive to subsequent addition of the iron chelators.
      Pretreatment with Triton X-100 resulted in significant potentiation of the
      ability of ferrous chloride (II) to inhibit [3H]MK-801 binding irrespective of
      the addition of agonists, moreover, although binding of other radioligands to the
      non-NMDA receptors was unaltered after pretreatment first with Triton X-100 and
      then with ferrous chloride (II). These results suggest that ferrous ions (II) may
      interfere selectively with opening processes of the NMDA channel through
      mechanisms entirely different from those underlying the inhibition by both SNP
      (II) and potassium ferrocyanide (II) in rat brain.

PMID- 9231736
TI  - Characterization of glutamate-induced formation of N-acylphosphatidylethanolamine
      and N-acylethanolamine in cultured neocortical neurons.
AB  - Glutamate-induced formation of N-acylethanolamine (NAE) and N
      acylphosphatidylethanolamine (NAPE) was studied in primary cultures of mouse
      neocortical neurons prelabeled with [14C] ethanolamine. The formation of these
      two lipids was dependent on the maturity of the cell culture; i.e., no glutamate
      induced formation was seen in 2-day-old cultures, whereas glutamate induced a
      pronounced formation in 6-day-old cultures. The calcium ionophore A23187 (2
      microM) stimulated, within 2 h, formation of NAPE in 2-day-old cultures
      (fourfold) as well as in 6-day-old cultures (eightfold). Glutamate exerted its
      effect via NMDA receptors as seen by the inhibitory action of the NMDA-selective
      receptor antagonists D-(-)-2-amino-5-phosphonovalerate and N-(1-(2
      thienyl)cyclohexyl)piperidine and the lack of effect of the alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid (AMPA)/kainate-receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). In 6-day-old cultures, exposure to NMDA (100
      microM for 24 h) induced a linear increase in the formation of NAPE and NAE as
      well as a 40-50% neuronal death, as measured by a decrease in cellular formazan
      formation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay]. The increase in NAPE and NAE could be detected earlier than the neuronal
      death. Neither cyclic AMP, cyclic GMP, nitric oxide, protein kinase C, nor
      peroxidation appears to be involved in the formation of NAPE and NAE, as assessed
      by the use of different pharmacological agents. Exposure to 5 mM NaN3 for 8 h
      resulted in a >80% decrease in the cellular MTT staining and a pronounced linear
      increase in the formation of NAE and NAPE (reaching 25-30% of total labeling).
      [14C]Anandamide was also formed in [14C]arachidonic acid-labeled neurons exposed
      to NaN3. No NAPE formation was detected in A23187-stimulated mouse astrocytes,
      rat Leydig cells and cardiomyocytes, and several other cells. These results
      suggest that the glutamate-induced formation of NAPE and NAE was mediated by the
      NMDA receptor and the formation of these lipids may be associated with neuronal
      death.

PMID- 9231737
TI  - Cross talk between substance P and melittin-activated cellular signaling pathways
      in rat lactotroph-enriched cell cultures.
AB  - We have investigated the possible interaction (cross talk) between the
      phospholipase A2 (PLA2) and inositol 1,4,5-trisphosphate/protein kinase C (PKC)
      signaling pathways in rat lactotroph-enriched cell cultures. Melittin, a bee
      venom peptide, stimulated release of [3H]arachidonic acid ([3H]AA) from [3H]AA
      labeled enriched lactotrophs in a dose-dependent manner. Moreover, melittin and
      exogenous AA induced a redistribution of PKC catalytic activity and PKC alpha and
      beta immunoreactivity from the soluble to the particulate fraction in resting and
      substance P (SP)-stimulated cells. Melittin had no effect on phospholipase C
      (PLC) activity. Pretreatment of cell cultures with the PLA2 inhibitors quinacrine
      and aristolochic acid resulted in a dose-dependent inhibition of melittin
      stimulated PKC isozyme translocation as did the inhibitor of lipoxygenase,
      nordihydroguaiaretic acid, whereas the cyclooxygenase inhibitor indomethacin had
      no effect. SP and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA)
      dose-dependently increased levels of [3H]AA released from cells. Pretreatment of
      cell cultures with quinacrine reduced the effect of SP on [3H]AA formation. After
      long-term treatment (24 h) of cells with TPA, the effect of TPA on [3H]AA
      production was not different from control, whereas SP still displayed [3H]AA
      releasing abilities although not at full scale. Pretreatment of cells with
      thapsigargin, U 73122, methoxyverapamil, and RHC 80267, an inhibitor of
      diacylglycerol lipase, all resulted in reduced SP-stimulated [3H]AA liberation.
      Treatment of cell cultures with pertussis toxin (PTX) reduced the release of
      [3H]AA induced by SP, whereas PTX had no effect on SP-stimulated generation of 3H
      inositol phosphates. On the basis of these results, it is concluded that (1) the
      PLA2 pathways interfere with the phosphoinositide-PLC signaling system at the
      level of PKC isozymes alpha and beta, the product responsible for this
      interaction being either AA or a metabolite produced by the action of
      lipoxygenase; (2) SP and TPA are able to activate the PLA2 pathway at a level at
      or beyond PLA2, and this effect is mediated, in part, through PKC alpha and beta
      species and (for SP) intracellular Ca2+ recruited from internal stores as well as
      from external sources; and (3) SP also activates PLA2 through a PTX-sensitive
      pathway distinct from the one coupled to phosphoinositide-PLC, which is PTX
      insensitive.

PMID- 9231738
TI  - Biochemical analysis of myelin proteins in a novel neurological mutant: the taiep
      rat.
AB  - Hemispheres, spinal cords, and sciatic nerves were taken from taiep, carrier, and
      control rats at ages ranging from 1 day to 16 months. Absolute myelin yields from
      CNS taiep tissues peaked at approximately 2 months and then decreased until they
      reached a low but stable level. Myelin yield from the affected hemispheres
      expressed as a percentage of age-matched controls decreased continuously from 2
      weeks until it reached a stable level of approximately 10-15%. The same was true
      for the spinal cords, but here the myelin yield reached a plateau at a slightly
      higher percentage of 20-25%. In comparison with control rats, isolated CNS myelin
      fractions from the affected rats had a greater content of high molecular weight
      proteins. Western blot analyses of CNS homogenates revealed that myelin basic
      protein (MBP), proteolipid protein, and 2',3'-cyclic nucleotide 3'
      phosphodiesterase were all present but decreased to levels generally consistent
      with the deficiencies of myelin. However myelin-associated glycoprotein (MAG)
      levels always were reduced much more than those of the other three myelin
      proteins, and at younger ages the apparent molecular weight for MAG was increased
      in the mutants. Western blot analyses of sciatic nerve homogenates showed that
      the levels of MBP, MAG, and P0 were not significantly different in control and
      mutant animals. These results suggested an early hypomyelination of the CNS, with
      peak levels of myelin at 2 months, followed by a prolonged period of myelin loss,
      until a very low but stable myelin level was reached. The consistently greater
      loss of MAG, in comparison with other CNS myelin proteins, is different from most
      other hypomyelinating mutants in which MAG is relatively preserved in comparison
      with the proteins of compact myelin. This might be due to microtubular
      abnormalities in the taiep mutant interfering with transport of myelin proteins
      and having the greatest effect on MAG because of its most distal location in the
      periaxonal oligodendroglial membranes.

PMID- 9231739
TI  - p53-knockout mice are protected against the long-term effects of methamphetamine
      on dopaminergic terminals and cell bodies.
AB  - p53-knockout mice provide a useful model to test the role of p53 in the
      neurotoxic effects of drugs in vivo. To test the involvement of p53 in
      methamphetamine (METH)-induced toxicity, wild-type mice, as well as heterozygous
      and homozygous p53-knockout male mice, were administered four injections of three
      different doses (2.5, 5.0, and 10.0 mg/kg) of the drug given at 2-h intervals
      within the space of 1 day. METH caused a marked dose-dependent loss of dopamine
      transporters in both the striatum and the nucleus accumbens of wild-type mice
      killed 2 weeks after drug administration. However, this METH-induced decrease in
      dopamine transporters was attenuated in both homozygous and heterozygous p53
      knockout mice, with homozygous animals showing significantly greater protection.
      The possibility for p53 involvement in METH-induced toxicity was also supported
      by the observation that METH caused marked increases in p53-like immunoreactivity
      in the striata of wild-type mice and very little change in heterozygous p53
      knockout mice, whereas no p53-like immunostaining was detected in the homozygous
      p53-knockout mice. Further support for p53 involvement was provided by the fact
      that METH treatment caused significant decreases in dopamine transporter mRNA and
      the number of tyrosine hydroxylase-positive cells in the substantia nigra pars
      compacta and the ventral tegmental area of wild-type but not homozygous p53
      knockout mice killed 2 weeks after cessation of METH administration. These
      results provide concordant evidence for a role of the tumor suppressor, p53, in
      the long-term deleterious effects of a drug acting on brain dopamine systems.

PMID- 9231740
TI  - Functional mapping of dorsal and median raphe 5-hydroxytryptamine pathways in
      forebrain of the rat using microdialysis.
AB  - Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT)
      pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus
      (MRN) have measured extracellular 5-HT in brain regions with reported
      preferential DRN or MRN 5-HT inputs. Here, we have tested whether electrical
      stimulation of the DRN and MRN releases 5-HT in rat forebrain regions in a
      pattern that fits the reported distribution of DRN/MRN pathways. The effect on
      extracellular 5-HT of electrical stimulation (5 Hz, 300 microA, 20 min) of the
      DRN, and then MRN, was determined in six regions of the anaesthetised rat.
      Stimulation of the DRN evoked a short-lasting but clear-cut release of 5-HT (+70
      100%) in regions (frontal cortex, dorsal striatum, globus pallidus, and ventral
      hippocampus) reported to receive a 5-HT projection from the DRN. Regions
      receiving an MRN innervation (dorsal hippocampus, medial septum, and ventral
      hippocampus) released 5-HT (+70-100%) in response to MRN stimulation. Regions
      reported to receive a preferential DRN innervation (frontal cortex, dorsal
      striatum, and globus pallidus) did not respond to MRN stimulation. Of two regions
      (dorsal hippocampus and medial septum) reported to receive a preferential MRN
      innervation, one did not respond to DRN stimulation (dorsal hippocampus) although
      the other (medial septum) did. In summary, electrical stimulation of the DRN and
      MRN released 5-HT in a regionally specific pattern. With the exception of one
      region (medial septum), this pattern of release bears a strong relationship to
      the distribution of 5-HT projections from the DRN and MRN reported by anatomical
      studies. The combination of raphe stimulation with microdialysis may be a useful
      way to study the in vivo neurochemistry of DRN/MRN 5-HT pathways.

PMID- 9231742
TI  - GABA(A) receptors containing the alpha4-subunit: prevalence, distribution,
      pharmacology, and subunit architecture in situ.
AB  - Recombinant GABA(A) receptors, expressed from alpha-, beta-, and gamma2-subunits,
      are diazepam-insensitive when the alpha-subunit is either alpha4 or alpha6. In
      situ, diazepam-insensitive receptors containing the alpha6-subunit are almost
      exclusively expressed in the granule cell layer of the cerebellum. However,
      diazepam-insensitive receptors are also expressed in forebrain areas. Here, we
      report on the presence of diazepam-insensitive GABA(A) receptors in various brain
      areas containing the alpha4-subunit. GABA(A) receptors immunoprecipitated with a
      newly developed alpha4-subunit-specific antiserum displayed a drug binding
      profile that was indistinguishable from those of alpha4beta2gamma2-recombinant
      receptors and diazepam-insensitive [3H]Ro 15-4513 binding sites in rat brain
      membranes. In addition, alpha4-subunit containing receptors and forebrain
      diazepam-insensitive receptors are present at comparably low abundance in rat
      brain and exhibit virtually identical patterns of distribution. Analysis of the
      subunit architecture of alpha4-subunit containing receptors revealed that the
      alpha4-subunit contributes to several receptor subtypes. Depending on the brain
      region, the alpha4-subunit can be coassembled with a second type of alpha-subunit
      variant being alpha1, alpha2, or alpha3. The data demonstrate that native
      receptors containing the alpha4-subunit are structurally heterogeneous, expressed
      at very low abundance in the brain, and display the drug binding profile of
      diazepam-insensitive [3H]Ro 15-4513 binding sites. Pharmacologically, these
      receptors may contribute to the actions of nonclassical ligands such as Ro 15
      4513 and bretazenil.

PMID- 9231741
TI  - Mechanisms of GABA- and glycine-induced increases of cytosolic Ca2+
      concentrations in chick embryo ciliary ganglion cells.
AB  - We used fura-2 microfluorometry and the gramicidin-perforated patch clamp
      technique in an attempt to clarify the mechanisms underlying the GABA- and
      glycine-induced increases in the cytosolic Ca2+ concentration ([Ca]in) in acutely
      isolated chick embryo ciliary ganglion neurons. GABA, glycine, and isoguvacine,
      but not baclofen, increased [Ca]in in a dose- and a Ca2+-dependent manner. The
      GABA-induced [Ca]in increase was inhibited by bicuculline and picrotoxin, and
      potentiated by pentobarbital, flunitrazepam, and alphaxalone, whereas the glycine
      induced [Ca]in increase was inhibited by strychnine but not by bicuculline or
      picrotoxin. L- and N-type Ca2+ channel blockers inhibited the GABA- and glycine
      induced [Ca]in increases, whereas Bay K-8644 potentiated these responses. These
      responses were also substantially potentiated by blockers of various K+ channels
      and by lowering the external Cl- concentrations. The high KCI- and nicotine
      induced [Ca]in increases were substantially reduced during continuous stimulation
      with either 2 microM GABA or 1 mM glycine. Electrophysiological studies indicated
      that the reversal potential of the GABA-induced current exhibited a more
      depolarized value than the resting membrane potential in 17 of the 25 cells
      examined. Taken together, these results suggest that both GABA and glycine
      depolarize the membrane potentials by increasing Cl- conductance via respective
      receptors and thus increase the Ca2+ influxes through L- and N-type voltage
      dependent Ca2+ channels.

PMID- 9231743
TI  - Effects of milnacipran and pindolol on extracellular noradrenaline and serotonin
      levels in guinea pig hypothalamus.
AB  - Milnacipran, a dual noradrenaline (NA) and serotonin (5-hydroxytryptamine, 5-HT)
      uptake inhibitor, increased extracellular levels of NA and 5-HT in hypothalamus
      of freely moving guinea pigs as measured by microdialysis. The basal levels of
      both monoamines, which were tetrodotoxin sensitive, were increased in a dose
      dependent manner and to a similar extent after the intraperitoneal administration
      of milnacipran (10 and 40 mg/ kg i.p.). Levels of the NA metabolite 4-hydroxy-3
      methoxyphenylglycol (MHPG) were decreased by milnacipran at 10 and 40 mg/kg i.p.,
      whereas those of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) showed
      no effect. Subcutaneous injection of 5-HT1A and beta-adrenergic receptor
      antagonist (-)-pindolol alone, at 10 mg/kg, had no effect on the extracellular
      levels of NA or 5-HT. The concomitant administration of (-)-pindolol (10 mg/kg
      s.c.) with milnacipran (10 mg/kg i.p.) increased severalfold the effect of
      milnacipran on the extracellular levels of NA and 5-HT. These results indicate
      that milnacipran, by blocking the uptake of NA and 5-HT, increases virtually
      equipotently the extracellular levels of NA and 5-HT, confirming previous in
      vitro studies. In addition, the antagonism of 5-HT1A autoreceptors by (-)
      pindolol potentiates the action of milnacipran on both NA and 5-HT systems,
      without modifying the ratio of these activities.

PMID- 9231744
TI  - Transfection of reaggregating embryonic chicken retinal cells with an antisense
      5'-DNA butyrylcholinesterase expression vector inhibits proliferation and alters
      morphogenesis.
AB  - The function of the enzyme butyrylcholinesterase (BChE) in the developing and
      mature brain is still unclear. We have inserted 577 bp of the 5' upstream region
      plus 106 bp of the exon 1 of the rabbit BChE gene in reverse orientation under
      control of an SV40 early promoter derivative in an expression vector. This vector
      was introduced by calcium phosphate-mediated transfection into embryonic chicken
      retina cells during the first days of reaggregation culture. Depending on the
      retinal origin, the transfected cell population forms histotypic retina-like
      spheres, so-called rosetted or stratified retinospheroids. We show that antisense
      5'-BChE gene expression decreased the steady-state mRNA level of BChE and the
      translation of the BChE protein, inhibited proliferation, and accelerated
      histogenesis in both cellular systems. The pronounced effects of antisense 5'
      BChE transfection of spheroids document a key role of BChE during the early
      reaggregation process of retinal cells, most likely by regulating their growth
      and differentiation.

PMID- 9231745
TI  - Two-dimensional characterization of paired helical filament-tau from Alzheimer's
      disease: demonstration of an additional 74-kDa component and age-related
      biochemical modifications.
AB  - PHF-tau proteins are the major components of the paired helical filament (PHF)
      from Alzheimer's disease (AD) neurofibrillary lesions. They differ both
      qualitatively and quantitatively in their degree of phosphorylation when compared
      with native tau proteins. However, little is known about the extent and
      heterogeneity of phosphorylated sites or the isoform composition and the
      isoelectric variants of PHF-tau. Therefore, we have characterized PHF-tau
      proteins from cortical brain tissue homogenates of 13 AD patients using two
      dimensional gel electrophoresis. Whatever the topographical origin of brain
      tissue homogenates, PHF-tau proteins shared the same two-dimensional gel
      electrophoresis profile made of a tau triplet of 55, 64, and 69 kDa. A 74-kDa
      hyperphosphorylated tau component was detected particularly in the youngest and
      most severely affected AD patients. This additional component of
      hyperphosphorylated tau was shown to correspond to the longest brain tau isoform.
      Furthermore, the isoelectric points of PHF-tau from older AD patients were
      significantly more basic, indicating a lower degree of phosphorylation. These
      results show that the severity of neurofibrillary degeneration of AD is modulated
      by age.

PMID- 9231746
TI  - Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide
      phosphodiesterase by dihydropyridine calcium antagonists.
AB  - Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) is one of the
      key enzymes involved in the complex interaction between the cyclic nucleotide and
      Ca2+ second-messenger systems. CaMPDE exists as tissue-specific isozymes, and
      initially these isozymes were designated according to their respective subunit
      molecular mass. A variety of pharmacological agents have been used to inhibit
      CaMPDE, and this inhibition occurs mostly via Ca2+-dependent association with the
      proteins. We have examined the effect of dihydropyridine Ca2+-channel blockers
      felodipine and nicardipine on CaMPDE. The results suggest that the 63-kDa (PDE
      1B1) and 60-kDa (PDE 1A2) CaMPDE isozymes are inhibited by felodipine and
      nicardipine by partial competitive inhibition and that these two Ca2+ antagonists
      appear to counteract each other. This study further demonstrates the existence of
      a specific site, distinct from the active site on CaMPDE, that exhibits high
      affinity binding of these drugs. Felodipine and nicardipine have similar
      affinities for 60-kDa CaMPDE isozymes but bring about different levels of enzyme
      inhibition, suggesting the possibility of designing specific drugs that can
      protect the enzyme from inhibition by dihydropyridine Ca2+-channel blockers.

PMID- 9231747
TI  - Lipopolysaccharide and interleukin-1beta augmented histidine decarboxylase
      activity in cultured cells of the rat embryonic brain.
AB  - We investigated the effect of lipopolysaccharide (LPS) and various inflammatory
      cytokines on the histidine decarboxylase (HDC) activity in cultured cells of the
      rat embryonic brain. Histaminergic neuronal cell bodies were supposed to exist in
      cultured cells of the diencephalon but not in those of the cortex. The HDC
      activity was elevated by adding LPS and interleukin-1 beta (IL-1beta) but not by
      tumor necrosis factor-alpha (TNF-alpha) and IL-6 to the mixed primary cultures of
      diencephalon. In the adherent cell fraction of the cultured diencephalon cells,
      HDC activity was also enhanced by LPS and IL-1beta. In a similar manner, LPS
      augmented HDC activity in the mixed primary culture of cerebral cortical cells
      and in its adherent cell fraction. The effects of IL-1beta but not LPS in the
      mixed primary culture of diencephalon were canceled by a prior exposure to
      cytosine-beta-D-arabinofuranoside. The changes in HDC activity after exposure to
      LPS for 12 h were not accompanied by increased mRNA levels. In these cell
      cultures, mast cells were not detected by Alcian Blue staining. These results
      indicated the presence of the third type of HDC-bearing cell besides neurons and
      mast cells in the brain. The increase of HDC activity by IL-1beta might be due to
      cell proliferation.

PMID- 9231748
TI  - Serum opens tight junctions and reduces ZO-1 protein in retinal epithelial cells.
AB  - We have shown previously that serum inhibits tight junction formation in a
      retinal epithelial cell culture model for the blood-brain barrier. We have now
      examined in detail the effects of serum on the tight junctions. Our data show
      that serum induces a breakdown in tight junction function as indicated by
      decreased transepithelial electrical resistance and increased permeability. Rat
      serum had effects similar to those of bovine serum, indicating that the activity
      is species-independent. The effect is concentration-dependent, reversible, and
      specific for the apical surface, suggesting the involvement of a specific
      receptor-ligand interaction. Differences in the time course, response magnitude,
      and structural manifestations between the serum-induced breakdown and that
      induced by switching the cultures to a low-calcium medium suggest fundamental
      differences in their mechanisms. The calcium switch results in an immediate and
      complete junctional breakdown with cell retraction and perinuclear translocation
      of both actin and the tight junction protein zonula occludens-1. The serum
      induced breakdown occurs slowly, is incomplete, and is manifested structurally by
      decreases in zonula occludens-1 protein, whereas actin organization is unchanged.
      Thus, serum induces a specific breakdown in retinal epithelial cell tight
      junctions that may be mediated by effects on the expression of zonula occludens
      1.

PMID- 9231749
TI  - Use of dipeptides for the synthesis of glutathione by astroglia-rich primary
      cultures.
AB  - The intracellular content of glutathione in astroglia-rich primary cultures
      derived from the brains of newborn rats was used as an indicator for the ability
      of these cells to use dipeptides for glutathione synthesis. For restoration of
      the glutathione level, after a 24-h starvation period in the absence of glucose
      and amino acids, glucose, glutamate, cysteine, and glycine have to be present in
      the incubation buffer. The dipeptides CysGly and gammaGluCys were able to
      substitute for cysteine plus glycine and glutamate plus cysteine, respectively.
      Half-maximal contents of glutathione were found at 20 microM CysGly and 3 mM
      gammaGluCys. In addition, the oxidized forms of the dipeptides CysGly and GlyCys
      could replace cysteine plus glycine for glutathione restoration, and the glycine
      containing dipeptides GlyGly, GlyLeu, GlyGlu, GlyGln, and gammaGluGly could
      partially substitute for the glycine necessary for the replenishment of
      glutathione. The glutathione resynthesis in the presence of CysGly plus glutamate
      was totally inhibited in the presence of buthionine sulfoximine, an inhibitor of
      gamma-glutamylcysteine synthetase. In contrast, glutathione restoration from
      gammaGluCys at a concentration of 10 mM in the presence of glycine was not
      influenced by the inhibitor. The use of CysGly or gammaGluCys was not affected by
      the presence of the dipeptidase inhibitors cilastatin or bestatin. In addition,
      carnosine and several other dipeptides applied in a 50-fold excess only slightly
      prevented the use of CysGly, hinting at the existence in astroglial cells of a
      transport system specific for CysGly. The results demonstrate that astroglial
      cells can use dipeptides for intracellular glutathione synthesis and that the
      dipeptides most likely are taken up as intact molecules into astroglial cells
      before intracellular hydrolysis occurs.

PMID- 9231750
TI  - Effect of cocaine on the histaminergic neuron system in the rat brain.
AB  - To examine the effect of cocaine on the brain histamine neuron system, histamine
      levels and histamine N-methyltransferase activity in the rat brain were measured
      after the administration of cocaine. Moreover, we examined the effect of L
      histidine on cocaine-induced wheel-running behavior. The administration of
      cocaine (20 mg/kg) increased histamine levels and histamine N-methyltransferase
      activity in the striatum, nucleus accumbens, and amygdala 1 h later. The
      pretreatment with L-histidine (350 and 700 mg/kg) inhibited the cocaine (20 mg/
      kg)-induced increase of wheel-running activity in a dose-dependent manner. These
      findings suggest that cocaine activates the brain histamine neuron system, which
      may play the role of inhibiting the cocaine-induced wheel-running behavior.

PMID- 9231751
TI  - Net glutamate release from astrocytes is not induced by extracellular potassium
      concentrations attainable in brain.
AB  - Elevated extracellular potassium concentration ([K+]e) has been shown to induce
      reversal of glial Na+-dependent glutamate uptake in whole-cell patch clamp
      preparations. It is uncertain, however, whether elevated [K+]e similarly induces
      a net glutamate efflux from intact cells with a physiological intracellular
      milieu. To answer this question, astrocyte cultures prepared from rat and mouse
      cortices were incubated in medium with elevated [K+]e (by equimolar substitution
      of K+ for Na+), and glutamate accumulation was measured by HPLC. With [K+]e
      elevations to 60 mM, medium glutamate concentrations did not increase during
      incubation periods of 5-120 min. By contrast, 45 min of combined inhibition of
      glycolytic and oxidative ATP production increased medium glutamate concentrations
      50-100-fold. Similar results were obtained in both rat and mouse cultures.
      Studies were also performed using astrocytes loaded with the nonmetabolized
      glutamate tracer D-aspartate, and parallel results were obtained; no increase in
      medium D-aspartate content resulted from [K+]e elevation up to 90 mM, whereas a
      large increase occurred during inhibition of energy metabolism. These results
      suggest that a net efflux of glutamate from intact astrocytes is not induced by
      any [K+]e attainable in brain.

PMID- 9231752
TI  - Differential vulnerability of the CA1 and CA3 subfields of the hippocampus to
      superoxide and hydroxyl radicals in vitro.
AB  - The relative roles of the superoxide and hydroxyl radicals in oxidative stress
      induced neuronal damage were investigated using organotypic hippocampal slice
      cultures. Cultures exposed to 100 microM duroquinone, a superoxide-generating
      compound, for 3 h developed CA1-selective lesions over a period of 24 h. The
      damage accounted for approximately 64% of the CA1 subfield, whereas CA3 showed
      just 6% damage, a pattern of damage comparable to that observed following
      hypoxia/ischaemia. Duroquinone-induced damage was attenuated by a spin-trap
      agent. In contrast, hydroxyl radical-mediated damage, generated by exposure to 30
      microM ferrous sulphate for 1 h, resulted in a CA3-dominant lesion. The damage
      developed over 24 h, similar to that observed with duroquinone, but with
      approximately 45% damage in CA3 compared with only 7% in CA1. These data
      demonstrate a selective vulnerability of the CA1 pyramidal neurones to superoxide
      induced damage and suggest that of the free radicals generated following
      hypoxia/ischaemia, superoxide, rather than hydroxyl radical, is instrumental in
      producing neuronal damage.

PMID- 9231753
TI  - Parathyroid hormone and osteocalcin--when friends become strangers.

PMID- 9231754
TI  - Parathyroid hormone (PTH 1-34) regulation of rat osteocalcin gene transcription.
AB  - Osteocalcin (OC) is a bone-specific extracellular matrix protein expressed by
      mature osteoblasts during late stages of differentiation. Previous studies have
      shown that forskolin, an activator of adenylate cyclase, stimulated OC
      production. Because PTH has been shown to activate several intracellular signal
      transduction pathways including cAMP, inositol phosphate and intracellular
      calcium mobilization, we investigated whether PTH action on cAMP accumulation
      leads to OC promoter activation. The rat OC promoter (1095 bp) was cloned into
      the promoterless luciferase gene reporter vector. The transcriptional activity of
      the rat OC promoter was evaluated after transfection of SaOS-2, an osteosarcoma
      cell line, with the OC promoter followed by treatment with PTH. Maximal OC
      promoter activity was observed within 4-8 h after the addition of 10(-8) M PTH,
      whereas very little induction was seen after 24 and 48 h of treatment. The
      induction of OC promoter activity by PTH was concentration dependent. PTH analogs
      (PTH 1-84, PTH 1-34, and PTH 1-31) that stimulate intracellular cAMP
      accumulation, induced OC promoter activity, whereas other PTH analogs (PTH 3-34,
      PTH 7-34, PTH 13-34, and PTH 53-84) that do not stimulate cAMP production had no
      effect on OC promoter activation. Furthermore, PTH activation of the OC promoter
      was significantly enhanced in the presence of 3-isobutyl-1-methylxanthine (IBMX),
      a phosphodiesterase inhibitor. Inactivation of cAMP-dependent protein kinase A
      activity by either a selective protein kinase A inhibitor, H-89 (N-[2-(p
      bromocinnamylamino)ethyl]-5 isoquinolinesulfonamide), or antisense
      oligonucleotide directed against the regulatory subunit of cAMP-dependent protein
      kinase A, led to a corresponding loss of OC promoter activation by PTH. 5'
      deletion analysis of the OC promoter demonstrated that the promoter (1095 bp)
      exhibited the greatest response to PTH, whereas the -198 bp construct of the OC
      promoter, containing only one cAMP response element and OC box, was no longer
      responsive. The constructs with further deletions (-120, -92, and -74) retained
      PTH responsiveness, but to a lesser extent. In summary, our results indicate that
      PTH activation of the OC promoter is a rapid event and mediated by the cAMP
      dependent protein kinase A pathway. Although the novel cAMP response region
      overlapping the OC box is required for activation, full activation may require
      several cis-acting cAMP response elements or other response elements.

PMID- 9231755
TI  - Androgens modulate nitric oxide synthase messenger ribonucleic acid expression in
      neurons of the major pelvic ganglion in the rat.
AB  - Expression and androgen regulation of the gene for neuronal nitric oxide synthase
      (NOS I) were examined in neurons of the major pelvic ganglia in male rats. Some
      of these postganglionic neurons innervate the penis and produce nitric oxide,
      which is believed to play a major role in penile erection. Rats were either
      castrated or sham operated and implanted with SILASTIC brand capsules filled with
      powdered testosterone (T) or 5alpha-dihydrotestosterone (5alphaDHT) or left
      empty. After 4 days, the number of neurons intensely stained for NADPH-diaphorase
      as well as those giving a NOS I signal in in situ hybridization experiments
      increased in castrated rats treated with testosterone by 31% and 42%,
      respectively, relative to those in untreated castrated rats. This suggests that
      the increase in NADPH-diaphorase activity resulted from enzyme synthesis and was
      due to a modification of NOS I messenger RNA (mRNA) accumulation. After 7 days,
      Northern blot analysis showed that castration produced a decrease in the amount
      of NOS I mRNA relative to that of ribosomal RNA. This decrease was almost
      prevented by T treatment. No significant differences were observed by reverse
      transcriptase-PCR between 7-day and 28-day treatments. However, in 7-day
      castrated rats treated with 5alphaDHT, NOS I signals relative to those of
      hypoxanthine phosphoribosyltransferase, taken as reference, were significantly
      higher than those in castrated rats and resembled those in sham-castrated rats,
      suggesting that 5alphaDHT was probably more potent than testosterone in
      preventing the decrease in NOS I mRNA levels elicited by castration. These
      results show that NOS I can be positively regulated by androgens and are
      consistent with the suggestion that these steroids play a role in the
      physiological processes of penile erection.

PMID- 9231756
TI  - Role of mitogen-activated protein kinase pathway in prostaglandin F2alpha-induced
      rat puerperal uterine contraction.
AB  - In this study, prostaglandin (PG) F2alpha was found to activate mitogen-activated
      protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal
      uterine myometrial cells. PGF2alpha stimulation also led to an increase in
      phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we
      examined the mechanism by which PGF2alpha induced MAP kinase phosphorylation.
      Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression
      of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor
      kinase 1 (betaARK1), which specifically blocks signaling mediated by the
      betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP
      kinase. Ritodrine (1 microM), which is known to relax uterine muscle contraction,
      attenuated PGF2alpha-induced tyrosine phosphorylation of MAP kinase. Moreover, to
      examine the role of MAP kinase pathway in uterine contraction, an inhibitor of
      MEK activity, PD098059, was used. Although MEK inhibitor had no effect on
      PGF2alpha-induced calcium mobilization, this inhibitor partially inhibited
      PGF2alpha-induced uterine contraction. These results provide evidence that
      PGF2alpha stimulates the MAP kinase signaling pathway in cultured rat puerperal
      uterine myometrial cells through Gbetagamma protein, suggesting that this new
      pathway may play an important role in the biological action of PGF2alpha on these
      cells.

PMID- 9231757
TI  - Effect of fasting on insulin-like growth factor (IGF)-IA and IGF-IB messenger
      ribonucleic acids and prehormones in rat liver.
AB  - The insulin-like growth factor I (IGF-I) gene generates by alternative splicing
      two IGF-I messenger RNAs (mRNAs) coding for IGF-I prehormones with different E
      domain sequences. In rats, these two mRNAs differ by the presence (IGF-IB) or
      absence (IGF-IA) of a 52-bp insert in the E domain coding region. The purpose of
      this study was to investigate the effect of nutritional perturbation on IGF-IA
      and -IB expression in rat liver. Northern blot analysis of liver mRNA revealed
      that the 1.5-1.9 kb and 0.9-1.2 kb IGF-I mRNA species were decreased in rats
      fasted for 48 h compared with either fasted-refed (48 h of each) or control-fed
      rats (each, P < 0.01), whereas the 7.5 kb IGF-I mRNA was decreased only when
      compared with the fasted-refed animals. Using semiquantitative RT-PCR, the IGF-IA
      transcript (114 bp amplicon) was not altered, whereas the IGF-IB transcript (166
      bp amplicon) was decreased in fasted rats compared with the other two groups
      (both P < 0.01). We confirmed the RT-PCR results by RNase protection assay (RPA),
      observing that the IGF-IA (224 and 100 bases protected) was not decreased and
      that the IGF-IB transcript (376 bases protected), accounting for only 23% of the
      total IGF-I transcripts of control fed rats, was decreased by fasting. Because
      the results from RT-PCR and RPA do not necessarily predict full-length
      translatable mRNA, we subjected hepatic IGF-I transcripts to in vitro
      translation, and we immunoprecipitated IGF-IA and -IB prehormones. Both
      prehormones were translated principally from exon 1-containing mRNAs, with
      molecular weights of about 17K and 18K, representing 80% and 20% of the total IGF
      I prehormones observed in control fed rats, respectively. Both peptides were
      reduced in fasted rats compared with controls (P < 0.01), and refeeding restored
      both. By immunoblotting of the protein extract from liver of fasted rats, IGF-IA
      was decreased by 77% compared with control-fed animals. Refeeding returned IGF-IA
      to normal. The lack of reduction of IGF-IA transcript at the alternative splice
      site suggests that posttranscriptional mechanisms are responsible for the
      reduction in steady-state IGF-I mRNAs that occurs during fasting. Additionally,
      we present evidence that biosynthesis of IGF-IA and -IB prehormones by liver is
      impaired at a posttranscriptional level.

PMID- 9231758
TI  - Lack of effect of thyroid hormone on late fetal rat brain development.
AB  - Studies were undertaken to test whether alterations in fetal brain thyroid
      hormone levels during the final week of gestation can prematurely induce gene
      expression in brain or affect cerebellar morphogenesis. Pregnant dams were
      treated either by administration of 0.025% methimazole (MMI) in the drinking
      water from day 14 post conception (PC14) or administration of 2.5 mg T4/100 g BW
      on PC15. On PC21, treatment with MMI resulted in a 53% fall in fetal brain T3
      levels and excess T4 resulted in a 2- to 3-fold increase to concentrations
      observed in adult brains. Neither excess nor reduced levels of T3 caused
      alterations in the expression of the myelin basic protein, Pcp-2 or calmodulin
      kinase IV genes. Cerebella of control brains showed early evidence of foliation
      and the presence of a several cell thick Purkinje cell layer and an external
      granule layer. No treatment induced effects were evident. Thus, at the late fetal
      stage in the rat, the developing brain appears to be unresponsive to thyroid
      hormone despite the presence of thyroid hormone receptors. We infer the presence
      of as yet unidentified factors that suppress precocious response to thyroid
      hormone or the absence of cofactors essential for such a response.

PMID- 9231759
TI  - Deletion of the thyroid hormone beta1 receptor increases basal and
      triiodothyronine-induced growth hormone messenger ribonucleic acid in GH3 cells.
AB  - The conserved diversity, restricted distribution, and differential regulation of
      the thyroid hormone receptor (TR) isoforms raise the possibility of isoform
      specific functions. We have addressed the roles of individual TRs in GH gene
      expression in GH3 cells by using an isoform-specific antisense RNA to delete
      TRbeta1. An antisense RNA vector, directed against the isoform-specific coding
      sequence of the parent TRbeta1 complementary DNA, was constructed. Stable
      transfected GH3-derived cell lines expressing this construct were established.
      Appropriate control cell lines were established in parallel. Depletion of TRbeta1
      in cells expressing the antisense construct was confirmed at both the messenger
      RNA and protein levels. Total TR expression was maintained in these cells by a
      reciprocal increase in TRbeta2 levels. This perturbation of the TR population was
      associated with a 10.5-fold increase in basal and a 5.0-fold increase in T3
      stimulated GH gene expression, but no increase in total T3 binding of nuclear
      extracts. In transient cotransfection experiments, there were no differences
      between control cells and those expressing the antisense construct in either
      basal or T3-stimulated expression of reporters containing a variety of thyroid
      hormone response elements. Depletion of TRbeta1 in GH3 cells results in a
      reciprocal increase in TRbeta2. These changes are associated with increased basal
      and T3-stimulated GH gene expression, which are not due to a nonspecific
      enhancement of basal or hormone-stimulated transcription. We demonstrate that
      TRbeta1 is not required for T3 induction of the GH gene in GH3 cells and that
      TRbeta1 and TRbeta2 are not equivalent in their effects on basal repression of
      the GH promoter. The data illustrate the potential for isoform- and promoter
      specific dissociation of the repression and activation properties of the TRs.

PMID- 9231760
TI  - Thyroid-specific expression of cholera toxin A1 subunit causes thyroid
      hyperplasia and hyperthyroidism in transgenic mice.
AB  - Thyroid cell growth and function are regulated by hormones and growth factors
      binding to cell surface receptors that are coupled via G proteins, Gs and Gq, to
      the adenylyl cyclase and phospholipase C signal transduction systems,
      respectively. Activating mutations of the TSH receptor and G alpha s have been
      documented in subsets of thyroid neoplasms. To test the oncogenic potential of
      activated G alpha s in transgenic mice, we used the cholera toxin A1 subunit that
      constitutively activates G alpha s and used the rat thyroglobulin gene promoter
      for targeting this transgene (TGCT) to thyroid follicular cells. Three (M1392,
      F1358, and F1286) of six founders identified were able to transmit the transgene
      to their offspring and thyroid glands from these mice contained elevated levels
      of cAMP. Concentrations of serum thyroxine were elevated as early as 2 months of
      age (M 1392 and F 1286). F1358 mice were euthyroid until 8 months of age, at
      which time they developed hyperthyroidism. All three TGCT lines developed thyroid
      hyperplasia independent of their thyroxine levels. DNA image analysis of thyroid
      follicular cells from both the hyper and euthyroid mice showed that DNA index and
      "S+G2/M" phase were increased compared with normal, changes similar to that seen
      in poor prognosis human carcinomas. These data suggest that the G alpha s
      adenylyl cyclase-cAMP pathway has an important role in thyroid hyperplasia and
      the transgenic mouse models reported herein will allow further examination of the
      role of this pathway in thyroid oncogenesis.

PMID- 9231761
TI  - Endothelin activates large-conductance K+ channels in rat lactotrophs: reversal
      by long-term exposure to dopamine agonist.
AB  - Endothelin-1 (ET-1) inhibits PRL secretion from cultured rat lactotrophs.
      However, ET-1 stimulates PRL secretion after cultured lactotrophs have been
      exposed for 48 h to dopamine or D2 dopamine agonists. In the present study, we
      have used cell-attached and inside-out patch recordings to establish an ionic
      basis for these effects. Bath application of 20 nM ET-1 to untreated lactotrophs
      evoked a robust and persistent activation of large-conductance K+ channels in
      cell-attached patches. This effect of ET-1 had a long latency to onset, was
      maintained for as long as ET-1 was present, and required at least 10 min of
      washing in control saline before complete recovery was achieved. The stimulatory
      effect of 20 nM ET-1 on these channels was markedly attenuated in the presence of
      the selective ET(A) receptor antagonist BQ-610 (200 nM), or after pertussis toxin
      (200 ng/ml, 16 h) pretreatment. The unitary slope conductance of the ET-1
      activated channels in cell attached patches was 165 and 95 pS when the recording
      electrodes contained 150 and 5.4 mM KCl, respectively. These channels were
      voltage-sensitive and their activity increased upon patch depolarization.
      Previously activated channels in cell-attached patches became quiescent
      immediately upon patch excision into Ca2+-free bath saline. Exposure of the
      intracellular surface to 0.1 microM Ca2+ restored the activity of these channels
      similar to the level seen before patch excision. In addition, preincubating the
      cells with the membrane-permeable Ca2+-chelator BAPTA-AM, or using Ca2+-free
      solution in the recording pipettes, prevented the activation of these channels by
      ET-1. The ET-1 activated large-conductance Ca2+-dependent K+ (BK(Ca)) channels
      were blocked by 20 mM tetraethylammonium but were insensitive to the K+ channel
      blockers apamin (1 microM), charybdotoxin (200 nM), or iberiotoxin (200 nM).
      Acute application of 10 microM dopamine and 20 nM ET-1 caused activation of
      BK(Ca) channels with indistinguishable kinetic properties, although the effect of
      dopamine occurred with shorter latency. After 48-h exposure to the specific D2
      dopamine receptor agonist (+/-)-2-(N-phenyl-N-propyl) amino-5-hydroxytetralin
      hydrochloride (PPHT, 500 nM), bath application of 20 nM ET-1 resulted in
      inhibition of spontaneously active BK(Ca) channels. These data suggest that both
      the stimulatory and inhibitory effects of ET-1 on PRL secretion are mediated, at
      least in part, by actions on BK(Ca) channels, and that long term exposure to
      dopamine or D2 agonists alters the signaling pathways from the ET(A) receptor to
      BK(Ca) channels.

PMID- 9231762
TI  - Expression of a murine gonadotropin-releasing hormone receptor-luciferase fusion
      gene in transgenic mice is diminished by immunoneutralization of gonadotropin
      releasing hormone.
AB  - A line of transgenic mice harboring a fusion gene consisting of 1900 bp of
      proximal 5'-flanking region from the murine GnRH receptor gene linked to the
      complementary DNA encoding luciferase was established to determine whether this
      promoter can direct tissue-specific expression in vivo and serve as a model for
      identifying the molecular mechanisms underlying hormonal regulation of this gene.
      Of 10 tissues screened, luciferase was detected predominantly in pituitary gland,
      but also in brain and testis. To assess hormonal regulation, luciferase activity
      was measured in intact males and ovariectomized females treated with an anti-GnRH
      serum alone, and in combination with testosterone or 17beta-estradiol. No effect
      of steroid treatment on transgene expression was detected. However,
      immunoneutralization of GnRH resulted in decreased serum LH concentrations and
      suppressed pituitary expression of luciferase. Furthermore, the effects of GnRH
      antiserum could be prevented by the administration of a noncross-reactive GnRH
      agonist. Thus, 1900 bp of 5'-flanking DNA from the murine GnRH receptor gene are
      sufficient to target luciferase expression in transgenic mice to established
      sites of GnRH receptor gene expression. Furthermore, we suggest that GnRH
      regulation of GnRH receptor gene expression is mediated by regulatory elements
      residing within 1900 bp of the 5'-flanking region.

PMID- 9231763
TI  - Oscillatory signaling and insulin release in human pancreatic beta-cells exposed
      to strontium.
AB  - Oscillatory signaling and insulin release were studied in isolated pancreatic
      islets and beta-cells obtained from human cadaveric organ donors. Taking
      advantage of Sr2+ as an analog for Ca2+, it was possible to demonstrate glucose
      induced rhythmic activity in individual beta-cells identified by immunostaining.
      Glucose-induced slow oscillations of Sr2+ (frequency, 0.1-1.0/min) were sometimes
      seen at a sugar concentration as low as 3 mM. Addition of 20 nM glucagon resulted
      in a broadening of the oscillations or in their transformation into sustained
      elevation. Moreover, the presence of glucagon resulted in the appearance of short
      transients of Sr2+, which disappeared after exposure to the intracellular Ca2+
      adenosine triphosphatase inhibitor thapsigargin. Digital image analyses indicated
      that slow oscillations can be synchronized among cells in small aggregates and
      intact islets. The rhythmic activity in the glucose-stimulated beta-cell had its
      counterpart in pulsatile insulin release when single islets were perifused with a
      Sr2+-containing medium. It is concluded that the human beta-cell has oscillatory
      signaling for insulin release similar to that observed in experimental animals.

PMID- 9231764
TI  - Developmentally regulated expression and activity of 17alpha-hydroxylase/C-17,20
      lyase cytochrome P450 in rat liver.
AB  - We have investigated the developmental pattern of expression and activity of
      17alpha-hydroxylase/C-17,20-lyase cytochrome P450 (cytochrome P450c17) in the
      liver, stomach, duodenum, and testis of rats from day 18 of pregnancy to
      adulthood. In the male liver, the enzyme became detectable at birth (135 pmol/mg
      protein x min) at a level comparable to that in the testis (188 pmol/mg protein x
      min). The activity then increased dramatically, reaching a peak at 8 days (691
      pmol/mg protein x min), which was more than 4-fold the testicular levels in rats
      of the same age or in adults. Thereafter it declined steadily, becoming
      undetectable from puberty onward. The hepatic peak followed a depression in
      testicular activity (58 pmol/mg protein x min) on day 6. Northern and immunoblot
      analyses showed a good temporal correlation between enzyme activity and the
      occurrence of P450c17 messenger RNA (mRNA) and protein. The same patterns of mRNA
      and protein occurrence were observed in female rat liver, indicating that the
      hepatic CYP17 expression is not sexually dimorphic. Sequencing confirmed a
      complete identity in the coding region between hepatic and gonadal mRNAs. Hepatic
      P450c17 mRNA, however, was 150-200 bases longer than the gonadal counterparts. No
      significant expression of mRNAs encoding P450scc and P450arom was observed in
      liver of either sex at any age. In stomach and duodenum, enzyme activity was much
      lower (maxima at 25 and 14 pmol/mg protein x min, respectively) than that in
      liver, but persisted from the time of weaning onward. It is suggested that the
      hepatic peak in P450c17 activity may serve to convert circulating progestogens
      into androgens for gonadal aromatization during Sertoli and granulosa cell
      proliferation.

PMID- 9231765
TI  - Retinoid X receptors in the kidney: their protein expression and functional
      significance.
AB  - Retinoid X receptors (RXRs) heterodimerize with 1,25-dihydroxyvitamin D3 (VD)
      receptor (VDR), and play important roles in VD-regulated transactivation. VD acts
      on many tissues including kidney for the regulation of calcium homeostasis. In
      the kidney, the expression of VDR in the tubular cells has been well studied. In
      contrast, little is known about the localization and the functional significance
      of RXRs there. In order to elucidate these questions, we first performed
      immunohistochemical analyses of rat kidney using isoform-specific antimouse RXR
      antibodies we have previously reported. Interestingly, all RXR isoforms,
      predominantly RXR alpha, mainly localized to the proximal and the distal tubules,
      but not to the glomeruli. The serial section staining using anti-VDR antibody
      showed the colocalization of RXR alpha and VDR in those tubular cells. In order
      to elucidate the functional significance of endogenous receptors in the tubular
      cells, we next performed transient transfection studies using the tubular-cell
      derived Madin-Darby bovine kidney cells, which express both endogenous VDR and
      RXR. We transfected a reporter plasmid containing direct repeat 3 (DR3) sequence,
      to which only RXR/VDR heterodimer can bind, and found that VD and 9-cis retinoic
      acid, as well as VD and RXR selective agonist LG100153, had an additive effect
      for the DR3 transactivation. Taken together, we speculate that endogenous RXRs co
      localize with VDR, and coregulate VD-dependent genes in the tubular cells of the
      kidney as RXR/VDR heterodimer.

PMID- 9231767
TI  - Prolactin receptor heterogeneity in bovine fetal and maternal tissues.
AB  - Study of diverse PRL actions at a variety of fetal and maternal targets during
      pregnancy is complicated by receptor heterogeneity and multiple ligands
      circulating at this time. In the present studies, we have examined PRL receptors
      at a variety of potential targets by reverse transcription-PCR and Western
      analysis. Bovine tissues contain two different transcripts for the PRL receptor;
      the one that encodes a short form includes an additional 39 bases at a position
      identical to the deviation from the long form found in rodents and sheep. Western
      analyses of PRL receptors in microsomal fractions from various maternal and fetal
      tissues revealed considerable size heterogeneity. Collectively, the larger
      immunoreactive moieties (apparent Mr 100 kDa or greater) and the smaller species
      (47-55 kDa) correlated well with the relative abundance of the transcripts for
      the different forms of the receptor and varied considerably among tissues. N
      Glycosylation was shown to be the major, but not the only, modification of both
      receptor forms when transiently transfected into COS-7 and END-6.2 cells. Much of
      the short form could be reduced to the mobility predicted from the complementary
      DNA by culture with tunicamycin; this was not true of the long form, suggesting
      modifications specific for its cytoplasmic domain. Differences in the pattern of
      immunoreactive species in the COS-7 and END-6.2 cells are consistent with cell
      specific modifications. The ability of these receptor forms to mediate a
      transcriptional response to PRL and its placental relative, placental lactogen,
      was evaluated with a PRL response element inserted upstream from a thymidine
      kinase promoter/reporter gene construct transiently transfected into CHO-K1
      cells. Both hormones were able to stimulate reporter gene expression through the
      long form, but not the short form, of the receptor. These studies will facilitate
      examination of tissue-specific actions of PRL and related hormones during
      pregnancy.

PMID- 9231766
TI  - Site-related specificities of the control by androgenic status of adipogenesis
      and mitogen-activated protein kinase cascade/c-fos signaling pathways in rat
      preadipocytes.
AB  - In rats, castration induces a complete defective adipose conversion of
      preadipocytes from the epididymal fat depots (Lacasa, D., B. Agli, D. Noynarol,
      and Y. Giudicelli, 1995, Endocrine 3: 789-793). The aim of this study was to
      establish the eventual site-specificity of this effect as well as the mechanisms
      involved. Therefore, the influence of androgenic status on the Fos protein
      induction and the Raf/mitogen-activated protein (MAP) kinase kinase (MEK)MAP
      cascade, which are all required for adipose conversion of preadipocytes, was
      compared in proliferating and differentiated preadipocytes from femoral sc and
      deep intraabdominal (epididymal and perirenal) fat depots. In epididymal and
      perirenal proliferating preadipocytes, increased proliferation due to castration
      is associated with increased MAP kinase activity. However, higher immunoreactive
      levels of the upstream activators of MAP kinase, Raf-1 and MEK, were observed
      only in epididymal cells. Moreover, in vivo testosterone treatment corrected the
      effects of castration on Raf-1 but not on MEK and MAP kinase. MAP kinase activity
      was decreased during the course of adipogenesis. In differentiated cells, MAP
      kinase activity showed variations according to the anatomical origin of
      preadipocytes but not to the androgenic status. In contrast, MEK and Raf-1
      immunoreactive levels were both sensitive to androgenic status but were
      differently affected depending on cell origin. Finally, the defective
      adipogenesis seen in epididymal preadipocytes from castrated rats was associated
      with reduced Fos protein induction in these cells, an alteration which was partly
      corrected by testosterone-treatment. Taken together, these results suggest that
      androgenic status affects adipogenesis from deep intraabdominal preadipocytes
      through alterations of some components of the MAP kinase cascade/Fos signaling
      pathways.

PMID- 9231768
TI  - Alterations in the insulin signaling pathway induced by immortalization and H-ras
      transformation of brown adipocytes.
AB  - In fetal brown adipocyte primary cultures, insulin rapidly (at 5 min) induced
      tyrosine phosphorylation of the insulin receptor beta-subunit; this effect was
      maximal at physiological concentrations (1 nM). Insulin also stimulated insulin
      receptor substrate-1 tyrosine phosphorylation and subsequently activated
      phosphatidylinositol 3-kinase. Moreover, a 3-fold increase in the Ras.GTP active
      form and a 6-fold increase in Raf-1 kinase activity were induced after insulin
      stimulation. An immortalized brown adipocyte cell line (by permanent simian virus
      40 large T antigen and pMEXneo cotransfection) showed a reduced maximal
      responsiveness to insulin in the same range of insulin concentrations studied (1
      100 nM). Transformed brown adipocyte cell line (by permanent simian virus 40
      large T antigen and pMEXneo H-ras(lys12) cotransfection) developed insulin
      resistance upstream from Ras, showing an impairment in the insulin receptor
      autophosphorylation, and in insulin receptor substrate-1 tyrosine phosphorylation
      and its association with phosphatidylinositol 3-kinase upon treatment with 1 nM
      insulin, although insulin receptor number and affinity (Kd) remained unaltered.
      This lack of effect was ameliorated upon treatment with higher insulin
      concentrations, in a dose-dependent manner. However, downstream from Ras, events
      such as formation of the Ras.GTP active form, and Raf-1 kinase and 12-O
      tetradecanoylphorbol-13-acetate response element-chloramphenicol transferase
      (transiently transfected) activities were overstimulated, compared with those in
      primary and immortalized cells, in an insulin-independent manner. Wheat-germ
      lectin-purified receptors from H-ras(lys12)-transformed brown adipocytes showed a
      marked phosphorylation in the basal state, which was suppressed by serine
      threonine phosphatase pretreatment. Moreover, alkaline phosphatase pretreatment
      restored the tyrosine kinase activity of the receptor in response to insulin. We
      conclude that the decreased tyrosine autophosphorylation rate of the insulin
      receptor from H-ras(lys12)-transformed brown adipocytes is a consequence of its
      basal serine/threonine phosphorylation, resulting in severe insulin resistance.

PMID- 9231769
TI  - Growth hormone-induced reorganization of the actin cytoskeleton is not required
      for STAT5 (signal transducer and activator of transcription-5)-mediated
      transcription.
AB  - We have investigated the effect of GH on the organization of the actin
      cytoskeleton within the cell. Human GH (hGH) treatment (50 nM) of Chinese hamster
      ovary (CHO) cells stably transfected with the complementary DNA for the rat GH
      receptor (CHO-GHR(1-638)) resulted in a reorganization of actin filaments in the
      cell that was not observed upon GH treatment of the untransfected parental CHO
      cell line. hGH initially induced depolymerization of actin stress fibers similar
      in magnitude to that induced by treatment of the cells with 100 nM human insulin
      like growth factor I. This loss of stress fibers was observed as early as 30 sec
      after addition of hGH to the medium, and maximal depolymerization of stress
      fibers was observed between 1-4 min after addition of hGH. This was followed by a
      slow, but submaximal, repolymerization of the stress fibers and the formation of
      localized focal filamentous actin containing complexes. Similar cytoskeletal
      changes were observed after hGH treatment in Swiss 3T3 fibroblasts and BRL cells
      stably transfected with rat GH receptor complementary DNA (BRL-GHR(1-6381)).
      Pretreatment of CHO-GHR(1-638) cells with wortmannin (a phosphatidylinositol 3
      kinase inhibitor) and verapamil (a calcium channel antagonist) both inhibited the
      hGH-induced actin reorganization. The integrity of the actin cytoskeleton was not
      required for GH-induced STAT5 (signal transducer and activator of transcription
      5)-mediated transcription, as treatment of cells with cytochalasins B and D did
      not alter the fold stimulation of the STAT5-mediated transcriptional response to
      GH. We conclude that GH induces a rapid reorganization of the actin cytoskeleton
      by a process requiring phosphatidylinositol 3-kinase activation and calcium
      influx, but this cytoskeletal reorganization is not required for the STAT5
      mediated transcriptional response to GH.

PMID- 9231771
TI  - Placenta-specific expression of the rat growth hormone-releasing hormone gene
      promoter in transgenic mice.
AB  - GH-releasing hormone (GHRH) is a hypothalamic peptide that plays a critical role
      in controlling the synthesis and secretion of GH in the anterior pituitary. Along
      with many other hypothalamic hormones, GHRH is also expressed in the placenta,
      although its physiological role in this tissue has not yet been determined. The
      placental prepro-GHRH is identical to that found in the hypothalamus. However,
      the placental and hypothalamic GHRH messenger RNAs differ in the region
      corresponding to the untranslated exon 1. A combined mechanism involving the use
      of tissue-specific promoters and the differential splicing of exon 1 generates
      the mature GHRH messenger RNAs in placenta and hypothalamus. As a first step
      toward the localization of the regulatory elements involved in the placenta
      specific expression of the GHRH gene, we have generated transgenic mice
      containing constructs in which potential regulatory sequences of the rat GHRH
      gene were fused to the chloramphenicol acetyltransferase (CAT) reporter gene.
      Construct GHRH-CAT1, which contains 7.5 kilobases of flanking sequences upstream
      to the placental transcription start site, did not promote CAT expression in the
      transgenic animals. In contrast, construct GHRH-CAT2, which differs from
      construct GHRH-CAT1 in having additional sequences located downstream to
      placental exon 1, exhibited high levels of CAT expression in brain and placenta.
      Our results show that the sequences included in construct GHRH-CAT2 contain the
      cis-acting regulatory elements necessary to direct developmentally regulated and
      cell type-specific expression of the CAT gene in the placenta. Unexpectedly, the
      expression of the transgene in the brain was detected in glial cells of different
      areas, but not in the hypothalamus.

PMID- 9231770
TI  - PRAP, a prolactin receptor associated protein: its gene expression and regulation
      in the corpus luteum.
AB  - We have recently identified, characterized, and cloned a luteal microsomal 32-kDa
      phosphoprotein that we named PRAP (for PRL-receptor associated protein), and we
      have demonstrated that PRAP binds to the intracellular domain of the short but
      not the long form of the PRL receptor. In this study, we used PRAP cDNA to
      examine the tissue specificity, the developmental expression, and the hormonal
      regulation of PRAP gene expression. Northern blot analysis revealed that in the
      corpus luteum, PRAP cDNA hybridized to multiple transcripts (5.5 kb, 4.3 kb, and
      1.8 kb), with the smallest transcript (1.8 kb) corresponding to the size of the
      cDNA clone. However, none of these transcripts were detected in any other tissues
      examined. PRAP appears to be tightly regulated by steroids and PRL. When pregnant
      rats were treated with aminoglutethimide, a steroid synthesis inhibitor, all
      three PRAP transcripts became barely detectable. Similar results were obtained
      when all luteotropic support was removed by hypophysectomy and hysterectomy.
      Estradiol up-regulated PRAP expression and, more specifically, the two lower
      transcripts. PRL had no stimulatory effect on PRAP messenger RNA (mRNA)
      expression but caused a substantial increase in the level of PRAP protein when
      administered to hypophysectomized pregnant rat, suggesting that PRL may stabilize
      this protein. Similar dissociation between levels of mRNA and protein were
      observed during luteal development. Although both PRAP mRNA and protein were
      barely detectable in early pregnancy, their expression increased abruptly from
      midpregnancy; however, whereas levels of PRAP mRNA declined from day 18, those of
      the protein remained elevated until parturition. In summary, results of this
      study have defined the tissue specificity and developmental expression of PRAP
      mRNA during pregnancy. The data have also revealed that the gene expression of
      this protein is up-regulated by estradiol, suggesting a pivotal role for PRAP in
      the synergistic action of estradiol and PRL on the function of the rat corpus
      luteum.

PMID- 9231772
TI  - Pituitary adenylate cyclase activating polypeptide stimulates rat Leydig cell
      steroidogenesis through a novel transduction pathway.
AB  - The aim of the present study was to evaluate the effects of pituitary adenylate
      cyclase activating polypeptide (PACAP) on testosterone production in isolated
      adult rat Leydig cells and its possible mechanisms of action. PACAP-38 stimulated
      testosterone secretion in a dose-dependent manner with a minimal and a maximal
      efficacious dose of 1.0 nM and 100 nM, respectively. PACAP-27 was without effect
      on testosterone secretion at any dose tested. Similarly, vasoactive intestinal
      peptide did not stimulate steroidogenesis nor interfere with PACAP-38 activity,
      as well as preincubation of Leydig cells with the vasoactive intestinal peptide
      antagonist [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-vasoactive intestinal peptide.
      Removal of extracellular Ca2+ did not inhibit the stimulatory effects of PACAP-38
      on Leydig cell testosterone production. Neither PACAP-38 nor PACAP-27 modified
      intracellular free Ca2+ and cAMP levels at any dose tested thus excluding a role
      for Ca2+ and cAMP in the stimulatory effects of PACAP. PACAP-38 was able to
      induce a plasma membrane depolarization that was dependent on an influx of Na+
      from the extracellular medium as confirmed by the monitoring of intracellular Na+
      with the Na+-sensitive fluorescent dye sodium benzofuran isophtalate. When Na+
      was removed from the extracellular medium, PACAP-38 did not stimulate
      testosterone production, demonstrating that Na+ influx through the plasma
      membrane is strictly related to the stimulatory effects of this peptide. In
      addition, preincubation of Leydig cells in the presence of pertussis-toxin (500
      ng/ml for 5 h) significantly reduced PACAP-38-stimulated effects both on plasma
      membrane depolarization and testosterone secretion. These results demonstrate
      that PACAP-38 stimulates testosterone secretion in isolated adult rat Leydig
      cells through the interaction with a novel PACAP receptor subtype coupled to a
      pertussis toxin sensitive G protein whose activation induces a Na+-dependent
      depolarization of the plasma membrane and testosterone production.

PMID- 9231773
TI  - Interaction of mouse placental lactogens and androgens in regulating progesterone
      release in cultured mouse luteal cells.
AB  - Pituitary hormones are essential for the maintenance of the corpus luteum in the
      pregnant mouse during the first half of gestation. Thereafter, hormones from the
      placenta take over the luteotropic role of the pituitary hormones. Mouse
      placental lactogen-I (mPL-I) and mPL-II, two PRL-like hormones produced in the
      placenta, are probably necessary for the maintenance of the corpus luteum in the
      latter half of pregnancy. A culture system of luteal cells from pregnant mice was
      developed to investigate the role of hormones from the placenta that may be
      important for the function of the corpus luteum. Mice were killed on days 10, 14,
      and 18 of pregnancy, and the corpora lutea were excised from the ovaries and
      digested in 0.1% collagenase, 0.002% DNase for 1 h. The resulting luteal cell
      suspension was plated onto 96-well plates coated with fibronectin (1 x 10(5)
      cells/well) and cultured for 1-3 days. Medium was changed daily. The cells were
      treated with various concentrations and combinations of mPL-I, mPL-II, mouse PRL,
      androstenedione, dihydrotestosterone, 17beta-estradiol (E2), testosterone,
      hydroxyflutamide, cycloheximide, actinomycin D, and fadrozole to study the
      effects of these different treatments on progesterone (P4) production. The three
      lactogens (mPL-I, mPL-II, and mouse PRL) all stimulated the release of P4 from
      the luteal cells. The potency of the lactogens was similar and did not depend on
      the stage of pregnancy at which the luteal tissue was obtained. However, the
      responsiveness of the cells to all hormone-stimulated P4 release was gradually
      reduced the later in pregnancy the tissue was collected. Androgens also
      stimulated the release of P4 from the luteal cells, and when administered
      together, the lactogens and the androgens acted synergistically to stimulate P4
      release. The androgens acted directly but not through conversion to E2, as
      determined by the findings that 1) the effects of the androgens could not be
      reproduced by E2 administration, 2) nonaromatizable androgen dihydrotestosterone
      was as effective as aromatizable androgens, and 3) aromatase inhibitor did not
      prevent the action of the androgens to stimulate the P4 release. The effect of
      the androgens on the P4 release was rapid, occurring within 15 min of hormone
      administration. It was not prevented by inhibitors of protein and RNA synthesis,
      and the intracellular androgen receptor antagonist hydroxyflutamide did not
      affect the androgen action. Therefore, the androgen effects were not mediated
      through the intracellular androgen receptor and de novo protein synthesis was not
      needed for androgen-stimulated P4 release.

PMID- 9231774
TI  - 3,5-diiodo-L-thyronine stimulates type 1 5'deiodinase activity in rat anterior
      pituitaries in vivo and in reaggregate cultures and GH3 cells in vitro.
AB  - Local deiodination of L-thyroxine (T4) to the active thyroid hormone T3 via two
      5'deiodinase isoenzymes (5'DI and 5'DII) plays an important role for various T3
      dependent functions of the anterior pituitary (AP). Recently, it was reported
      that 3,5-T2, the 5'deiodination product of T3, acts as a specific agonist in the
      feedback mechanism on TSH secretion at the pituitary level. We now examined the
      effects of 3,5-T2 on pituitary 5'deiodinase activities in vivo in male, adult
      rats and in vitro using rat AP reaggregate cultures and the somatomammotroph cell
      line GH3. 5'DI activity in the AP was transiently increased after a single
      injection of 3,5-T2. Serum TSH levels declined, and 24 h after 3,5-T2
      application, betaTSH steady-state mRNA levels in the APs were markedly lower. In
      reaggregate cultures of the AP, 3,5-T2 stimulated 5'DI activity 24 h after
      application, dose-dependently. Compared with 5'DI activities, those of 5'DII were
      an order of magnitude lower, in vivo as well as in vitro, and were rapidly and
      transiently decreased by the higher dose of 3,5-T2. GH3 cells responded to 3,5-T2
      and T3 by an 1.7-fold stimulation of 5'DI activity. Stimulation of DNA-binding
      was demonstrated in electrophoretic mobility shift assays for a specific RXR
      containing protein complex with a DR+4 thyroid hormone response element of the
      human type 1 5'DI promoter using nuclear extracts from GH3 cells treated with 3,5
      T2. In summary, 3,5-T2 and T3 exert direct thyromimetic effects on 5'DI activity
      and TSHbeta expression at the pituitary level. 5'DI is regulated by its
      substrate(s) and/or products and may serve an important function within the
      modulation of thyroid hormone-dependent gene expression in the AP.

PMID- 9231775
TI  - Chronic cold in adrenalectomized, corticosterone (B)-treated rats: facilitated
      corticotropin responses to acute restraint emerge as B increases.
AB  - Small elevations in corticosterone (B) administered exogenously exert potent
      inhibitory effects on both basal and stress-induced ACTH secretion. However,
      under conditions of chronic stress with chronic elevations in B, the hypothalamo
      pituitary-adrenal system appears to balance the negative feedback signal of B
      with central neural facilitation so that the system remains fully responsive to
      acute stressors. In these studies, we tested whether: 1) circulating B
      concentrations affect responses to acute restraint in rats exposed to 5 days at 5
      7 C (cold), compared with room temperature (control); and 2) facilitated ACTH
      secretion can be explained by increased CRF or vasopressin messenger RNA (mRNA)
      levels in the hypothalamic parvocellular paraventricular nuclei (PVN). Rats were
      adrenalectomized and supplied with B in doses that fixed plasma B at constant
      levels between approximately 2 and 20 microg/dl; rats were placed in cold or
      remained as controls. Increasing concentrations of fixed B decreased basal ACTH
      similarly in both groups. By contrast, as B levels increased, ACTH responses to
      restraint also increased in cold vs. control rats. Semiquantitative analysis of
      CRF mRNA by in situ hybridization revealed decreases of similar magnitude in both
      groups with increasing fixed B. Vasopressin mRNA levels also decreased with
      increasing fixed B in both groups, but with slightly less sensitivity to
      inhibition by B in cold exposed rats. Taken together, the decreases in mRNA for
      these major ACTH neuropeptide secretogogues in the parvocellular PVN are unlikely
      to explain facilitated ACTH responses in chronically stressed rats. We conclude
      that a brain site is stimulated by B that is proximal to the PVN; feedforward,
      positive effects of B are thus implicated in mediation of prior stress-induced
      facilitation of acute hypothalamo-pituitary-adrenal responses to stress.

PMID- 9231776
TI  - Identification, isolation, and characterization of a 41-kilodalton protein from
      rat germ cell-conditioned medium exhibiting concentration-dependent dual
      biological activities.
AB  - In this report, we describe the purification of a novel protease with dual
      biological actions from germ cell-conditioned medium (GCCM) where germ cells were
      isolated from adult rat testes using a mechanical procedure. Using multiple HPLC
      columns and two sequential high performance electrophoresis chromatography steps
      in association with an [125I]-collagen film assay to detect protease activity, a
      41-kDa polypeptide (41-kDa-P) was purified to apparent homogeneity from GCCM.
      Partial N-terminal amino acid sequence analysis of the purified protein revealed
      a sequence of NH2-KYEFYEIXLL that, when compared with the existing database at
      Protein Identification Resource (PIR), GenBank, and BLAST revealed that this is a
      unique protein. The purified protein, when incubated with [125I]-testin, a
      Sertoli cell secretory product that is localized at the intertesticular cell
      junction and is resistant to tryptic digest, was found capable of hydrolyzing
      testin dose dependently. The proteolysis of [125I]-testin by this 41-kDa protein
      was inhibited by alpha2-macroglobulin (a Sertoli cell secretory product) also in
      a dose-dependent manner. A study on the interactions between different classes of
      protease inhibitors and the purified 41-kDa protein revealed that it is a serine
      protease. At doses ranging between 0.5 and 50 ng/ml, 41-kDa-P induced a dose
      dependent inhibition of Sertoli cell secretory function using testin and
      clusterin as markers without any apparent proteolytic activity. However, at doses
      greater than 0.5 microg/ml, 41-kDa-P was found to cleave [125I]-collagen and
      [125I]-testin at physiological pH, indicating that this 41-kDa protein has dual
      biological activities whose primary action is concentration dependent. In view of
      the biological activities of this protease, it is postulated that this protein
      may be involved in facilitating germ cell migration in the epithelium.

PMID- 9231777
TI  - Tamoxifen attenuates glucocorticoid actions on bone formation in vitro.
AB  - Tamoxifen is a synthetic estrogen analog which may regulate osteogenesis in vivo
      by virtue of its antiglucocorticoid properties. We have examined tamoxifen
      regulation of glucocorticoid-induced osteogenesis in two different in vitro bone
      systems: the chicken periosteal osteogenesis model (CPO) and rat bone marrow
      stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma
      cell line, ROS 17/2.8. In the CPO model, alkaline phosphatase (AP) activity and
      collagen synthesis were stimulated by the glucocorticoid dexamethasone (Dex; 0.1
      microM). These Dex-mediated effects were inhibited by increasing concentrations
      of tamoxifen (10-100 microM). Similarly, in the RBMC model, Dex-dependent (0.01
      microM Dex) mineralized tissue formation and AP activity were blocked by
      tamoxifen (0.1 microM). Although tamoxifen inhibited Dex-mediated increases of AP
      activity in ROS 17/2.8 cells, it did not inhibit uptake of 3H-Dex or of 3H
      estrogen. Northern analyses showed that tamoxifen did not affect messenger RNAs
      (mRNAs) for AP. Tamoxifen did seem to reduce mRNA for collagen type I, but not
      bone sialoprotein, osteopontin, and osteocalcin. Dex-induced increases for all
      proteins mRNAs in the RBMC model were not reduced by tamoxifen. Similarly,
      tamoxifen had no effects on cellular proliferation. We conclude that tamoxifen
      has no direct effect on gene expression of bone-related proteins of osteoblastic
      cells. Further, in the ROS 17/2.8 cell line, the antiglucocorticoid properties of
      tamoxifen do not appear to be mediated through either Dex or estrogen receptors.

PMID- 9231778
TI  - Lipoprotein metabolism in the fat Zucker rat: reduced basal expression but normal
      regulation of hepatic low density lipoprotein receptors.
AB  - Hyperlipoproteinemia is one of the phenotypic characteristics of the fat Zucker
      rat that carries a mutation in the leptin receptor gene. In the present study, we
      studied the regulation of hepatic low density lipoprotein (LDL) receptor
      expression in lean and fat Zucker rats. Compared with lean rats, the fat ones had
      a pronounced (approximately 60%) reduction in hepatic LDL receptor expression,
      whereas the levels of receptor messenger RNA (mRNA) were not reduced. Fat rats
      had increased levels of very low density lipoproteins and high density
      lipoproteins, but their plasma apo B100 within LDL was reduced. Challenge with 2%
      dietary cholesterol for 8 days suppressed hepatic LDL receptor expression in lean
      animals to similar levels as seen in fat ones, whereas the reduction in mRNA
      levels was much less pronounced. Treatment with ethynylestradiol (5 mg/kg BW per
      day) for 4 days strongly stimulated hepatic LDL receptor expression in both lean
      and fat rats; this treatment also increased LDL receptor mRNA levels, but to a
      lesser extent. In conclusion, the basal expression of hepatic LDL receptors is
      reduced in fat Zucker rats, but the capacity for the regulation of the receptors
      remains intact.

PMID- 9231779
TI  - Identification of a nuclear protein from rat developing brain as
      heterodimerization partner with thyroid hormone receptor-beta.
AB  - Thyroid hormone receptors (TR) are ligand-activated transcription factors that
      modulate the expression of certain target genes in a developmental and tissue
      specific manner. These specificities are determined by the tissue distribution of
      the TR isoforms alpha1 and beta1, the structure of the thyroid hormone response
      element (TRE) bound by the receptor, and heterodimerization partners. Among
      these, retinoid X receptors (RXR) have been recognized as the principal partners
      for TR. The present work reports the identification of a novel nuclear protein
      from 19-day-old embryonic rat brain that displays a distinct interaction pattern
      with TR isoforms at the level of the TRE of two genes known to be differentially
      expressed and regulated by thyroid hormone (T3): the ubiquitous malic enzyme and
      the brain-specific myelin basic protein. Electrophoretic gel mobility shift
      assays demonstrate that only TRbeta1 forms a specific complex with the rat brain
      nuclear factor on the myelin basic protein-TRE, but not on the malic enzyme-TRE.
      Thus, the interaction is selectively determined by both the receptor isoform and
      the structure of the TRE. The expression of this brain nuclear factor is
      restricted to the perinatal period, when myelination is sensitive to T3. Gel
      supershift assays with RXR-specific antibodies indicate that this factor is not
      one of the known RXR isoforms. However, it is most likely a new member of the RXR
      subfamily because it could be supershifted with an antibody raised against the
      highly conserved DNA-binding domain of RXRs.

PMID- 9231780
TI  - 1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are
      androgen-dependent.
AB  - We and others have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25
      (OH)2D3] significantly inhibits cell proliferation and increases secretion of
      prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human
      prostate cancer cell line. The present study was designed to investigate the
      possible interactions between 1,25-(OH)2D3 and androgens in the regulation of
      LNCaP cellular function. LNCaP cell growth was dose-dependently inhibited by 1,25
      (OH)2D3 (60% inhibition at 10 nM) when cells were cultured in medium supplemented
      with FBS (FBS medium). 1,25-(OH)2D3-treated cells showed a 5-fold increase in PSA
      secretion, similar to the increase seen in dihydrotestosterone (DHT)-treated
      cells. In combination, 1,25-(OH)2D3 and DHT synergistically enhanced PSA
      secretion 22-fold. This synergistic effect was even greater when cells were
      cultured in medium supplemented with charcoal-stripped serum (CSS medium), where
      endogenous steroids are substantially depleted. Under these conditions, 1,25
      (OH)2D3 and DHT together stimulated PSA secretion up to 50-fold over the
      untreated control. Radioligand binding assays and Western blot analyses showed
      that the androgen receptor (AR) content was increased significantly by 1,25
      (OH)2D3 at 48 h. Furthermore, the steady-state mRNA level of AR was up-regulated
      approximately 2-fold by 1,25-(OH)2D3 at 24 h. When cells were grown in CSS
      medium, 1,25-(OH)2D3 alone no longer inhibited cell growth or induced PSA
      secretion. Titration experiments revealed that the addition of DHT at 1 nM to the
      medium restored the antiproliferative activity of 1,25-(OH)2D3. Conversely, an
      antiandrogen, Casodex, completely blocked 1,25-(OH)2D3 antiproliferative and PSA
      stimulation activities when cells were cultured in FBS medium. In conclusion,
      these results demonstrate that the antiproliferative and PSA induction activities
      of 1,25-(OH)2D3 in LNCaP cells are dependent upon androgen action and that AR up
      regulation by 1,25-(OH)2D3 likely contributes to the synergistic actions of 1,25
      (OH)2D3 and DHT in these cells.

PMID- 9231781
TI  - Association of the G protein alpha(q)/alpha11-subunit with cytoskeleton in
      adrenal glomerulosa cells: role in receptor-effector coupling.
AB  - In 3-day primary cultures of rat glomerulosa cells, a 30-min pre-incubation with
      either 10 microM colchicine (a microtubule-disrupting agent) or 10 microM
      cytochalasin B (a microfilament-disrupting agent) decreased angiotensin II (Ang
      II)-induced inositol phosphate accumulation by 50%. Moreover, both drugs
      decreased inositol phosphate production induced by fluoroaluminate (a nonspecific
      activator of all G proteins), indicating that both microtubules and
      microfilaments are essential for phospholipase C activation. Analysis of
      microfilament- and microtubule-enriched fractions and immunoprecipitation of
      actin and tubulin revealed that the alpha(q)/alpha11-subunit of the G(q/11)
      protein was associated with both structures. Ang II stimulation induced a rapid
      translocation of alpha(q)/alpha11, microfilaments, and microtubules to the
      membrane and induced a time-dependent increase in the level of alpha(q)/alpha11
      associated with both microfilaments and microtubules. Moreover, double
      immunofluorescence staining clearly showed a colocalization of the
      alpha(q)/alpha11-subunit of the G(q/11) coupling protein and microfilament
      distribution. These associations and plasma membrane redistribution under Ang II
      stimulation indicate that microfilaments and microtubules are both involved in
      phospholipase C activation and inositol phosphate production. Moreover, our
      results indicate that the alpha(q)/alpha11 protein is closely associated with
      cytoskeletal elements and is found both at the plasma membrane level as well as
      on intracellular stress fibers.

PMID- 9231782
TI  - Galparan: a powerful insulin-releasing chimeric peptide acting at a novel site.
AB  - Galparan is a 27-amino acid long chimeric peptide, GWTLNSAGYLLGP-INLKALAALAKKIL
      amide, consisting of galanin-(1-13) linked to mastoparan amide via a peptide bond
      to provide the mastoparan and galanin effector parts of the molecules. Galparan
      (10 microM) powerfully stimulates insulin secretion from isolated rat pancreatic
      islets in a reversible and dose-dependent manner; the stimulation is 26-fold at
      3.3 mM glucose and 6-fold at 16.7 mM glucose. Galparan also enhances insulin
      secretion to a similar extent from islets of diabetic GK rats. The stimulatory
      effect of galparan on insulin release is not directly dependent on extracellular
      Ca2+, nor can it be explained only by changes in free cytosolic Ca2+
      concentrations. Furthermore, galparan is effective in evoking insulin release in
      B cells depolarized by 25 mM KCl when ATP-sensitive K+ channels are kept open by
      diazoxide. Thus, galparan, like mastoparan, stimulates exocytosis of insulin at a
      distal site in the stimulus-secretion coupling of the B cell. This distal site is
      not identical to that used by mastoparan, as pertussis toxin pretreatment does
      not influence the insulinogenic effect of galparan. In conclusion, galparan
      evokes a large and reversible insulin secretion, acting at a yet unknown distal
      site and also promoting exocytosis in depolarized B cells from normal rats as
      well as diabetic GK rats.

PMID- 9231783
TI  - Testosterone acts directly at the pituitary to regulate gonadotropin-releasing
      hormone-induced calcium signals in male rat gonadotropes.
AB  - We have recently shown that castration alters GnRH-induced calcium (Ca2+)
      signaling in the gonadotropes of male rats. Instead of generating spike-plateau
      Ca2+ responses to high concentrations of GnRH (100 nM), the majority of
      gonadotropes from castrated rats have oscillatory Ca2+ responses, which are
      generally only seen with low concentrations of GnRH in the gonadotropes of intact
      rats. This change in the nature of GnRH-induced Ca2+ responses is prevented by in
      vivo testosterone treatment. The aims of the present study were, therefore, to
      determine if testosterone acts directly at the pituitary or via the regulation of
      hypothalamic GnRH secretion. Accordingly, castrated male rats were treated with a
      GnRH antagonist to ablate the effects of increased GnRH secretion at the
      pituitary gland. GnRH antagonist treatment (10 microg/100 g BW, twice daily for 7
      days from the time of castration) decreased the concentration of LH in the serum
      of castrated rats (0.4 +/- 0.1 ng/ml vs. 11.2 +/- 0.4 ng/ml in untreated
      castrated rats, mean +/- SEM) but had no effect on the proportion of gonadotropes
      having oscillatory Ca2+ responses to 100 nM GnRH when compared with untreated
      castrated rats (63% in antagonist-treated castrated rats vs. 70% in untreated
      castrated rats). The GnRH antagonist treatment did not, however, interfere with
      the ability of in vivo testosterone treatment (100 microg/100 g body weight/day)
      to decrease the proportion of gonadotropes having oscillatory Ca2+ responses to
      100 nM GnRH (26% in testosterone-treated rats vs. 25% in testosterone and
      antagonist-treated rats). These findings indicate that testosterone acts directly
      at the pituitary, and not by altered GnRH secretion, to modulate GnRH-induced
      Ca2+ signals. To confirm this suggestion, cultured gonadotropes of castrated male
      rats were treated in vitro with 10 nM testosterone. Testosterone treatment for
      twelve, but not 4 h, restored the proportion of gonadotropes having oscillatory
      Ca2+ responses to that seen in gonadotropes from intact rats. The in vitro
      effects of testosterone over 12 h were prevented by concomitant treatment with
      the protein synthesis inhibitor cycloheximide (10 microM), which, when given
      alone, had no effect on GnRH-induced Ca2+ signals in cells from castrate male
      rats. Taken together, these findings suggest that testosterone has a direct
      genomic action at the pituitary to regulate GnRH-induced Ca2+ signals, via a
      process that involves new protein synthesis.

PMID- 9231784
TI  - A role for neurotransmitters in early follicular development: induction of
      functional follicle-stimulating hormone receptors in newly formed follicles of
      the rat ovary.
AB  - The initiation of follicular growth in the mammalian ovary is a gonadotropin
      independent phenomenon. Although some of the intraovarian signaling molecules
      that control the later phases of this process have been recently identified, the
      factors involved in the acquisition of gonadotropin receptors by early growing
      follicles have not been fully defined. In the rat, development of the ovarian
      innervation precedes the onset of folliculogenesis and occurs before follicles
      acquire responsiveness to gonadotropins. Because vasoactive intestinal
      polypeptide (VIP) and norepinephrine (NE), two of the neurotransmitters contained
      in ovarian nerves, are present in the ovary before the gland becomes responsive
      to gonadotropins, we sought to determine if VIP and/or NE are able to act on
      early follicles to facilitate the process of molecular differentiation that leads
      to gonadotropin dependency. In vitro exposure of 2-day-old rat ovaries to
      isoproterenol (ISO), a beta-adrenoreceptor agonist, or VIP, a neurotransmitter
      contained in both sympathetic and sensory nerves, increased the steady state
      levels of the messenger RNAs encoding cytochrome P-450 aromatase (P-450arom) and
      FSH receptors (FSHR) within 8 h of treatment. A similar effect was observed
      following forskolin-induced activation of cAMP formation. In situ hybridization
      experiments revealed that both the P-450arom and FSHR hybridization signals were
      localized to follicles. The increase in FSHR messenger RNA was accompanied by
      formation of functional receptor molecules, as demonstrated by the ability of FSH
      to stimulate cAMP formation in ovaries preexposed to either ISO or VIP, but not
      in untreated ovaries. The stimulatory effect of ISO and VIP on the formation of
      FSHR coupled to the cAMP generating system was not reproduced by phenylephrine,
      an alpha-adrenergic agonist, or secretin, a member of the VIP family not
      recognized by ovarian VIP receptors. Treatment of VIP-primed ovaries with FSH
      resulted in follicular growth, demonstrating that exposure of the gland to the
      neurotransmitter led to the formation of a functional complement of FSH
      receptors. These results suggest that ovarian nerves, acting via
      neurotransmitters coupled to the cAMP generating system, contribute to the
      differentiation process by which newly formed primary follicles acquire FSH
      receptors and responsiveness to FSH. Follicles that begin to grow in more densely
      innervated ovarian regions, may have a selective advantage over those not exposed
      to neurotransmitter-activated, cAMP-dependent signals and, thus, may become more
      rapidly subjected to gonadotropin control.

PMID- 9231785
TI  - Estrogen and progesterone inhibit vascular smooth muscle proliferation.
AB  - Estrogen (E) has been identified in epidemiologic and prospective studies to
      protect against the development of cardiovascular disease in women. It is unclear
      whether progesterone (P) is similarly beneficial. The mechanisms by which E or P
      might act are incompletely defined. One possibility is that sex steroids inhibit
      the proliferation of vascular smooth muscle, an early/important event in vascular
      pathology. We examined the ability of E and P to inhibit the growth of human
      umbilical vein smooth muscle cells (hUVSMC) in culture, when stimulated by serum
      or the mitogen, endothelin-1 (ET-1). Serum and ET-1 stimulated hVSMC cell numbers
      by approximately 110% and 43% respectively, compared with control, after 3 days
      in culture. This stimulation was maximally reversed 75% by E and 64% by P. No
      synergistic or additive effects of the two steroids were found. ET-1 and serum
      stimulated mitogen-activated protein kinase (MAP-K) and MAP-kinase kinase
      activities, and these were critical for mitogenesis. Mitogen-stimulated MAP
      kinase kinase and MAP-K activities were significantly inhibited by either E or P.
      The steroids also inhibited mitogen-stimulated c-fos and c-myc, downstream
      targets for MAP-K action. Critical signaling and molecular events through which
      mitogens stimulate VSMC proliferation can be significantly inhibited by E or P,
      providing a potential cellular mechanism for their vascular protective actions.

PMID- 9231786
TI  - Molecular mechanisms of reappearance of luteinizing hormone receptor expression
      and function in rat testis after selective Leydig cell destruction by ethylene
      dimethane sulfonate.
AB  - Considering the major role of LH in the control of Leydig cell (LC) development
      and function, we aimed to characterize further the pattern of LH receptor (LHR)
      expression in two experimental paradigms: the rat treated with ethylene dimethane
      sulfonate (EDS), in which the selective destruction of preexisting mature LCs
      induces the proliferation and differentiation of newly formed LCs, a process that
      takes place in the presence of high levels of gonadotropins; and the EDS-rat
      treated with a high dose of testosterone (EDS + T), in which the LH secretion is
      suppressed, and consequently LC development after EDS arrested. In EDS rats,
      serum T was suppressed and testicular LHR binding became undetectable on days 5
      and 15 after treatment. The pattern of LHR messenger RNA (mRNA) expression was
      profoundly modified: only one of the splice variants [1.8-kilobase (kb)]
      persisted, whereas the others disappeared. On days 20 and 45 after EDS, along
      with LC repopulation, serum T and LHR binding recovered, and the pattern of LHR
      mRNA expression gradually returned to that resembling controls. In EDS + T rats,
      a similar drop in testicular LHR binding and change in the pattern of LHR mRNA
      expression was detected on days 5 and 15 after treatment. However, on days 20 and
      45, no recovery either in LHR binding or in expression of the longer LHR mRNA
      splice variants was observed, showing that LH is needed to induce LHR expression
      in repopulating LCs, at least to a quantitatively significant level. To gain
      further insight into the mechanism(s) by which LH acts on LC precursors, the
      translational status of the 1.8-kb LHR transcript, persistently expressed after
      EDS, was analyzed and compared with that of the 6.8-kb message. In polysome
      distribution analysis of total testicular RNA, the 6.8-kb LHR message was highly
      associated with polysomes, whereas the 1.8-kb variant was mainly localized to
      prepolysomal fractions, both in control and EDS testes, thus predicting lower
      translational efficiency. In addition, considering that only LCs express LHRs in
      the testis, the time course of the reappearance of functional receptors was
      mapped by evaluating testicular responsiveness to human recombinant LH in vitro.
      No response to LH stimulation was detected 5 days after EDS. However, cAMP
      response to LH was observed on days 15 and 20, regardless of the presence of high
      (EDS) or suppressed (EDS + T) LH in the donor animal. Hence, the appearance of
      functional LHRs, qualitatively, can take place in the absence of measurable LH
      levels. In EDS-treated rats, the appearance of the cAMP response coincided with
      those of pregnenolone, progesterone, and T. In contrast, no LH-induced steroid
      release was observed in EDS + T rats, indicating that steroidogenic response in
      developing LC requires LH priming. In conclusion, the appearance of functional
      LHRs, at a low level of expression, in LC precursors is an LH-independent
      developmental event, essential for the subsequent LH-dependent maturational
      steps, including the onset of steroidogenesis and increased LHR expression. In
      addition, our results cast doubt on a major functional role of the truncated (1.8
      kb) form of LHR mRNA, which persists after EDS at a high level of expression, in
      the early Leydig cell precursors.

PMID- 9231787
TI  - Direct administration of insulin-like growth factor to fetal rhesus monkeys
      (Macaca mulatta).
AB  - A potential treatment for the amelioration of fetal growth failure is insulin
      like growth factor-I (IGF-I). To address concerns of safety and efficacy, IGF-I
      (80 microg/kg; GroPep Pty.) was administered i.p. to healthy rhesus monkey
      fetuses via ultrasound guidance every other day between gestational days (GD) 110
      120 and 130-140 (third trimester; term = approximately GD 165 +/- 10; n = 6).
      Pregnancies were monitored sonographically, and fetal/maternal blood samples were
      collected for complete blood counts, immunophenotyping, and biochemical analyses.
      Blood samples, external measures of the fetus and newborn, and tissue and organ
      weights were collected at fetal necropsy (GD 150; n = 2) or at term delivery of
      neonates (GD 160; n = 4). The results of these investigations have shown no
      evidence of hypoglycemia in the fetus or dam during the course of treatment.
      Circulating concentrations of fetal, but not maternal, IGF-I increased with
      treatment (approximately 80 to approximately 1015 ng/ml), and there was no
      evidence of a change in serum IGF-II or an increase in IGF binding protein-3
      compared with historical control values. Fetal lymphocytes and select red cell
      parameters increased, and a significant elevation in circulating B cells and
      CD4/CD8 ratios in fetal lymph nodes was shown. Although no changes were detected
      in body weights, increases in thymic, splenic, and kidney weights and small
      intestine lengths occurred. Thus, administration of IGF-I to the fetal monkey is
      safe and results in 1) transient increases in circulating IGF-I, 2) a significant
      effect on fetal hematopoietic and lymphoid tissues, and 3) an increase in select
      fetal organ weights and measures. These data suggest that IGF-I may represent a
      potential candidate for therapeutic treatment of growth-compromised human fetuses
      in utero.

PMID- 9231788
TI  - Regional distribution of type 2 thyroxine deiodinase messenger ribonucleic acid
      in rat hypothalamus and pituitary and its regulation by thyroid hormone.
AB  - To identify the specific locations of type 2 deiodinase (D2) messenger RNA (mRNA)
      in the hypothalamus and pituitary gland and determine its regulation by thyroid
      hormone, we performed in situ hybridization histochemistry, Northern analysis,
      and quantitative RT-PCR in euthyroid, hypothyroid, and hyperthyroid rats. By in
      situ hybridization histochemistry, silver grains were concentrated over ependymal
      cells lining the floor and infralateral walls of the third ventricle extending
      from the rostral tip of the median eminence (ME) to the infundibular recess,
      surrounding blood vessels in the arcuate nucleus (ARC), and in the ME adjacent to
      the portal vessels and overlying the tuberoinfundibular sulci. Silver grains also
      accumulated over distinct cells in the midportion of the anterior pituitary. In
      hypothyroid animals, an increase in signal intensity was observed in the caudal
      hypothalamus, and a marked increase in the number of positive cells occurred in
      the anterior pituitary. Microdissection of the hypothalamus for Northern and PCR
      analysis established the authenticity of D2 mRNA in the caudal hypothalamus, and
      confirmed that the majority of D2 mRNA is concentrated in this region. The
      distribution of D2 mRNA suggests its expression in specialized ependymal cells,
      termed tanycytes, originating from the third ventricle. Thus, the tanycyte is the
      source of the high D2 activity previously found in the ARC-ME region of the
      hypothalamus. The results indicate that tanycytes may have a previously
      unrecognized integral role in feedback regulation of TSH secretion by T4.

PMID- 9231789
TI  - Aldosterone biosynthesis in the rat brain.
AB  - Messenger RNA (mRNA) for enzymes involved in adrenal steroid biosynthesis are
      expressed in the brain, and the coded enzymes have been shown to be active. The
      expression of mRNA for the cytochrome P-450 enzyme aldosterone synthase, crucial
      for the final step in the synthesis of aldosterone and the synthesis of
      aldosterone was studied in several anatomic areas of the rat brain. Expression of
      the mRNA for the aldosterone synthase was demonstrated by RT-PCR/Southern blot in
      adrenal, aorta, hypothalamus, hippocampus, amygdala, cerebrum, and cerebellum.
      Incubation of brain minces from intact and adrenalectomized rats demonstrated the
      synthesis of corticosterone and aldosterone from endogenous precursors.
      Incubations of brain minces with [1,2(3)H]-deoxycorticosterone, followed by
      extraction and three different successive TLCs, demonstrated the presence of
      labeled aldosterone, corticosterone, and 18-hydroxy-deoxycorticosterone.
      Incubation, in the presence of 10 microM cortisol or metyrapone, inhibited the
      synthesis of aldosterone or both aldosterone and corticosterone, respectively.
      These studies indicate that the rat brain has the enzymatic machinery for the
      synthesis of adrenal corticosteroids and is capable of synthesizing aldosterone.
      Aldosterone synthesized in the brain might play a paracrine role in the
      regulation of blood pressure.

PMID- 9231790
TI  - The adipose obese gene product, leptin: evidence of a direct inhibitory role in
      ovarian function.
AB  - Leptin, a recently-discovered hormonal product of the obese gene, circulates in
      the blood at levels paralleling those of fat reserves and regulates satiety and
      improves reproductive performance if injected into mice lacking circulating
      leptin. Therefore, we tested the hypothesis that leptin signals metabolic
      information to the reproductive system by directly affecting granulosa cell
      function. Doses of 10-300 ng/ml leptin had no effect (P > 0.10) on basal or
      insulin-induced numbers of granulosa cells cultured from small (1-5 mm) or large
      (> or = 8 mm) bovine follicles. Similarly, 30 and 300 ng/ml leptin had no effect
      (P > 0.10) on basal estradiol production. However, leptin, in a dose-dependent
      manner, inhibited (P < 0.05) insulin-induced progesterone and estradiol
      production by granulosa cells from small and large follicles. Leptin did not
      compete for specific 125I-insulin binding to granulosa cells. Furthermore,
      specific binding of 125I-leptin was demonstrable in granulosa cells. In
      conclusion, leptin, at physiological levels, can directly attenuate insulin
      induced steroidogenesis of granulosa cells without affecting proliferation of
      this ovarian cell type. These results provide evidence to support the hypothesis
      that leptin can act as a metabolic signal to the reproductive system via direct
      action at the ovarian level.

PMID- 9231791
TI  - Interleukin-6 and its soluble receptor regulate the expression of insulin-like
      growth factor binding protein-5 in osteoblast cultures.
AB  - Interleukin-6 (IL-6), a cytokine produced by bone cells, is known to influence
      bone resorption by stimulating the development of osteoclasts from precursor
      cells and to have mitogenic actions on osteoblastic cells. Insulin-like growth
      factors (IGFs) are important local regulators of bone formation, and IGF binding
      protein (IGFBP)-5 stimulates bone cell growth and enhances the effects of IGF-I.
      We tested the effects of IL-6 in the presence and absence of its soluble receptor
      (sIL-6R) on IGFBP-5 expression in cultures of osteoblast-enriched cells from 22
      day-old fetal rat calvariae (Ob cells). When tested individually, IL-6 and sIL-6R
      had a modest stimulatory effect on IGFBP-5 messenger RNA (mRNA) levels. In
      contrast, when IL-6 and sIL-6R were tested in combination, they caused a
      considerable increase in IGFBP-5 mRNA levels, and IL-6 at 100 ng/ml and sIL-6R at
      125 ng/ml increased IGFBP-5 transcripts by 5- to 7-fold after 24 h. The effect of
      IL-6 and sIL-6R on IGFBP-5 transcripts was not blocked by indomethacin, but
      cycloheximide markedly inhibited IGFBP-5 mRNA levels in control and treated
      cultures. IL-6 and sIL-6R did not modify the decay of IGFBP-5 mRNA in
      transcriptionally arrested Ob cells, and stimulated the rate of IGFBP-5
      transcription as demonstrated by a nuclear run-on assay. IL-6 and sIL-6R did not
      increase intact IGFBP-5 levels in the extracellular matrix and increased IGFBP-5
      fragments in the culture medium. Conditioned medium from Ob cells induced the
      proteolytic fragmentation of an IGFBP-5 standard, an effect that was accelerated
      and enhanced by conditioned medium from IL-6/sIL-6R-treated cultures and
      prevented by metalloprotease inhibitors. In conclusion, IL-6, in the presence of
      sIL-6R, stimulates IGFBP-5 mRNA expression in Ob cells by transcriptional
      mechanisms, and accelerates the fragmentation of the protein.

PMID- 9231792
TI  - Effect of dehydroepiandrosterone on bone mass, serum lipids, and
      dimethylbenz(a)anthracene-induced mammary carcinoma in the rat.
AB  - The present study investigated the effect of dehydroepiandrosterone (DHEA) on
      bone mass and serum lipids in the rat with dimethylbenz(a)anthracene (DMBA)
      induced mammary carcinoma. The animals received DHEA once daily, percutaneously,
      at the dose of 5, 10, or 20 mg for 9 months following a single dose of 20 mg DMBA
      at 50-52 days of age. Bone mineral content (BMC) and bone mineral density (BMD)
      of total skeleton, lumbar spine, and femur were measured by dual energy x-ray
      absorptiometry. A 9-month treatment with DHEA increased BMC and BMD of total
      skeleton by 14.2% to 14.5% (all P < 0.01) and 6.7% to 8.3% (all P < 0.01),
      respectively. Similarly, femoral BMC and BMD were stimulated by 13.6% to 14.7%
      (all P < 0.05) and by 8.1% to 9.5% (all P < 0.01), respectively. In addition, BMD
      of lumbar spine was increased by 10.4% to 10.8% (all P < 0.05), whereas the 9.4%
      to 11.1% increment in BMC of lumbar spine was not statistically significant.
      Treatment with DHEA led to 26% (NS), 60% (P < 0.01), and 62% (P < 0.01) decreases
      in serum triglyceride levels at the same doses. On the other hand, no significant
      change in serum cholesterol concentrations was observed. Two hundred and seventy
      nine days after DMBA administration, the incidence of mammary carcinoma had
      decreased from 95% in control animals to 73% (P < 0.05), 57% (P < 0.01), and 38%
      (P < 0.01) at the daily percutaneous doses of 5, 10, and 20 mg of DHEA,
      respectively. Moreover, the mean tumor number per tumor-bearing animal and the
      mean tumor area per tumor-bearing animal were also reduced by the same
      treatments. DHEA increased serum total alkaline phosphatase activity and
      decreased urinary calcium excretion, but had no effect on the urinary ratio of
      hydroxyproline to creatinine and urinary phosphorus excretion. These data show
      that DHEA exerts a stimulatory effect on bone mass and an inhibitory effect on
      serum triglycerides, as well as a preventive effect on the development of mammary
      carcinoma induced by DMBA in the rat. Such data suggest that while decreasing the
      risk of breast cancer, DHEA replacement therapy could also exert beneficial
      effects on the bone and lipid metabolism in women receiving DHEA replacement
      therapy.

PMID- 9231794
TI  - A critical period for thyroid hormone action on seasonal changes in reproductive
      neuroendocrine function in the ewe.
AB  - Thyroid hormones are obligatory for the annually recurring termination of
      reproductive activity in a spectrum of seasonal breeders, including sheep.
      Previous studies involving thyroidectomy and T4 replacement have led to the
      hypothesis that, in the ewe, thyroid hormones are necessary only during a limited
      interval late in the breeding season for the neuroendocrine processes that cause
      the transition to anestrus. The present series of experiments tested this
      hypothesis by assessing the influence of thyroidectomy, with or without T4
      replacement for specific durations and at different times of the year, on the
      transition to anestrus. Seasonal alterations in reproductive neuroendocrine
      activity were monitored by changes in serum LH concentration in ovariectomized
      ewes bearing s.c. SILASTIC brand silicon tubing implants containing estradiol.
      Thyroidectomy in mid-December, just before the putative period of thyroid hormone
      action, prevented the development of the neuroendocrine anestrous season (fall in
      LH in this animal model). T4 replacement for 90 days beginning in late December
      (i.e., during the postulated period of thyroid hormone action) overcame the
      blockade of anestrus, causing LH to fall in ewes thyroidectomized several months
      previously. The minimal effective duration of exposure to thyroid hormones
      required for the transition to anestrus was estimated to be 60-90 days. Further,
      exposure to T4 for 60-90 days beginning in late December was found to be the only
      time of the year that thyroid hormones were required to maintain seasonal changes
      in reproductive neuroendocrine activity. Finally, replacement of T4 for 90 days
      at a different time of year (beginning in August) failed to provoke development
      of neuroendocrine anestrus in thyroidectomized ewes. These results support the
      hypothesis that thyroid hormones are necessary only during a limited interval
      late in the breeding season to promote seasonal reproductive suppression in the
      ewe. Further, the reproductive neuroendocrine axis is not equally responsive to
      thyroid hormone at all times of the year. This suggests there is a critical
      period of responsiveness during which thyroid hormones must be present for
      anestrus to develop.

PMID- 9231793
TI  - Effects of leptin on insulin sensitivity in normal rats.
AB  - To determine whether leptin has insulin sensitizing effects in normal rodents, we
      measured plasma glucose and insulin concentrations in male Sprague-Dawley rats
      treated with leptin or vehicle by continuous s.c. infusion for 48 h. In
      additional experiments, we examined the acute effect of i.v. leptin upon insulin
      sensitivity under conditions of clamped glycemia. Subcutaneous leptin was
      administered at 10.0 and 1.0 microg/h. To avoid confounding effects of
      differences in food intake, both leptin- and vehicle-treated rats were fasted
      during the 48-h period of infusion. Infusion of leptin, 10 microg/h,
      significantly reduced both plasma glucose and insulin. Leptin, 1.0 microg/h, also
      decreased plasma glucose and insulin, although the effects on insulin did not
      achieve statistical significance. Leptin at either dose did not alter body weight
      or epididymal fat mass compared with vehicle treated controls. Leptin, 10
      microg/h, decreased circulating insulin-like growth factor-1 levels. No
      differences in GLUT-4 content in either in brown or epididymal fat were observed
      as a result of leptin-treatment. Leptin, 10 microg/h, significantly decreased
      urine osmolality, increased water intake, and reduced renal potassium excretion
      compared with vehicle-infused rats. In additional rats, we measured the acute
      effect of i.v. leptin on insulin sensitivity determined as whole body glucose
      utilization during hyperinsulinemic glucose clamps performed at glucose targets
      of 60 and 90 mg/100 ml. Glucose utilization was increased by 29% during the last
      135 min of glycemia clamped at 60 mg/100 ml (P < 0.05) and by 30% during the last
      135 min of glycemia clamped at 90 mg/dl (P < 0.01) in rats infused with leptin
      compared with vehicle. In summary, leptin increased insulin sensitivity in normal
      rats both under fasting conditions and in the presence of hyperinsulinemia at
      clamped glucose. These effects did not appear dependent on altered body weight.
      Leptin also altered salt and water metabolism under fasting conditions resulting
      in increased water intake and more dilute urine.

PMID- 9231795
TI  - Aldosterone rapidly represses protein kinase C activity in neonatal rat
      cardiomyocytes in vitro.
AB  - Aldosterone lowers protein kinase C (PKC) activity in myocyte-enriched cultures
      from neonatal Sprague-Dawley rat hearts, with activity measured by the transfer
      of phosphate to myristolated alanine-rich C-kinase substrate, in the presence of
      Ca2+, phosphatidylserine, and diolein. The effect is rapid, with a significant
      effect after 1 min exposure, half maximal at < or = 1 nM aldosterone, with
      steroids showing a hierarchy of potency aldosterone = 9alpha fluorocortisol >
      deoxycorticosterone > corticosterone > spironolactone. Both Ca2+-dependent and 
      independent PKC activity appear equally inhibited by aldosterone, and PMA
      stimulated increases in PKC activity appear similarly aldosterone-sensitive. No
      displaceable binding of [3H]aldosterone to purified PKC can be shown, evidence
      against a direct effect of aldosterone on PKC; aldosterone does not alter basal
      or PMA-stimulated PKC activity in cardiac fibroblasts, evidence for a cell
      specific mediator of the myocyte effect. Taken with the previous demonstration of
      the potentiation of aldosterone-specific MR-mediated effects by PKC activation,
      the present data argue for the existence of a complex cross-talk mechanism
      between aldosterone and factors affecting PKC activity in the heart.

PMID- 9231796
TI  - The proximal promoter region of the gene encoding human 17beta-hydroxysteroid
      dehydrogenase type 1 contains GATA, AP-2, and Sp1 response elements: analysis of
      promoter function in choriocarcinoma cells.
AB  - The 5'-flanking region from -78 to +9 in the HSD17B1 gene serves as a promoter,
      and an HSD17B1 silencer element is located in position -113 to -78. In the
      present studies, we have characterized three regulatory elements in the proximal
      5'-flanking regions of the gene, using electrophoretic mobility shift assays and
      reporter gene analysis. First, nuclear factors recognized by antibodies against
      Sp1 and Sp3 were found to bind the Sp1 motif in the region from -52 to -43.
      Mutation of the Sp1-binding site decreased the promoter activity to 30% in JEG-3
      cells and to 60% in JAR cells, suggesting that binding to the Sp1 motif has a
      substantial role in the complete functioning of the HSD17B1 promoter. Second, the
      binding of AP-2 to its motif in the region from -62 to -53 led to reduced binding
      of Sp1 and Sp3, and furthermore, mutation of the AP-2 element increased promoter
      activity to 260% in JEG-3 cells. The data thus implied that AP-2 can repress the
      function of the HSD17B1 promoter by preventing binding to the Sp1 motif. Finally,
      GATA factors, GATA-3 in particular, were demonstrated to bind their cognate
      sequence in the HSD17B1 silencer region, and mutations introduced into the GATA
      binding site increased transcriptional activity to the level seen in constructs
      not containing the silencer element. Thus, GATA-3 seems to prevent transcription
      in the constructs, and hence, the GATA motif also may operate as a negative
      control element for HSD17B1 transcription.

PMID- 9231798
TI  - Regulation of growth hormone (GH) gene expression and secretion during pregnancy
      and lactation in the rat: role of insulin-like growth factor-I, somatostatin, and
      GH-releasing hormone.
AB  - GH appears to play an important metabolic role during late pregnancy and in
      lactation maintenance. In this study, pregnant (days 8, 15, and 20 of gestation)
      and postpartum (days 3 and 8 postpartum, including lactating and nonlactating
      dams) Wistar rats were used to investigate pituitary GH gene expression and
      hormone secretion, and the potential alterations of the major signals regulating
      GH secretion and action [somatostatin (SS) and GH-releasing hormone (GHRH), GH
      receptor (GH-R), and insulin-like growth factor-I (IGF-I)]. GH and SS messenger
      RNA (mRNA) were quantitated by Northern blot, and both IGF-I and GH-R mRNA were
      analyzed by the ribonuclease protection assay technique. Pituitary IR-GH content
      and GH mRNA increased at midpregnancy. IR-GH content was decreased in lactating
      rats. Plasma GH levels progressively increased during pregnancy, whereas no
      significant alterations were shown during lactation. Elevated GH levels persisted
      during lactation. Levels at this time were higher in nonsuckling compared with
      suckling dams. Liver GH-R mRNA progressively decreased during pregnancy, but it
      remained unchanged during lactation. Plasma IGF-I and liver IR-IGF-I constantly
      decreased during pregnancy, and no significant modifications were seen either in
      suckling or in nonsuckling animals. IGF-I mRNA accumulation in the liver
      decreased during pregnancy. After delivery, a progressive decrease of liver IGF-I
      mRNA occurred. At the hypothalamic level, a progressive increase in the IR-SS
      content was found during pregnancy, with no SS mRNA modification. After delivery,
      a higher hypothalamic IR-SS content was found in lactating than in nonlactating
      rats, with no changes in SS mRNA levels. Hypothalamic IR-IGF-I also showed a
      progressive increase during pregnancy with no significant alterations during
      lactation. Hypothalamic IR-GHRH presented a nonsignificant mild increase during
      pregnancy with no modifications during lactation. In the pituitary, IR-IGF-I
      content progressively increased during gestation, reaching its highest
      concentration at day 20. During lactation, pituitary IGF-I did not change. In
      summary, our data show that the mechanisms of the increase in plasma GH levels
      occurring during pregnancy include an increase in GH gene expression in the
      pituitary, a decrease in SS secretion from the hypothalamus, an increase in IR
      IGF-I content in the hypothalamus and in the pituitary, and a significant
      decrease in circulating IGF-I. Plasma and liver IR-IGF-I and IGF-I mRNA in the
      liver decreased throughout gestation due to a lower GH-R gene expression in the
      liver. This state of GH resistance with a higher GH/IGF-I ratio could be
      important in providing supplementary nutrients to the fetus. During lactation, GH
      and its regulatory machinery did not show important modifications.

PMID- 9231797
TI  - Growth hormone-induced tyrosyl phosphorylation and deoxyribonucleic acid binding
      activity of Stat5A and Stat5B.
AB  - GH is known to activate JAK2 tyrosine kinase and members of the Stat family of
      transcription factors, including Stats 1, 3, and 5. The recent observation that
      at least two Stat5 proteins (Stat5A and Stat5B) exist in mouse and human, raises
      the question of whether GH activates both Stat5A and Stat5B and, if so, whether
      the requirements for activation are the same. An initial report investigating
      this issue demonstrated GH-dependent activation of Stat5A but not Stat5B. In this
      paper, we demonstrate (in COS cells expressing rat GH receptor (rGHR) and either
      Stat5A or Stat5B, 3T3-F442A fibroblasts, and CHO cells expressing rGHR) that GH
      induces tyrosyl phosphorylation of both Stat5A and Stat5B. Similar time courses
      of phosphorylation were observed for the two proteins. Interestingly, the pattern
      of observed bands differs for the two forms of Stat5. Two closely migrating
      Stat5A bands can be detected in cells treated with or without GH. Both of these
      bands become tyrosyl phosphorylated in response to GH. Three species of Stat5B
      are observed in untreated cells. An additional, more slowly migrating Stat5B
      band, appears upon treatment with GH. The three more slower migrating Stat5B
      bands observed in response to GH contain phosphorylated tyrosyl residues. We
      further demonstrate that GH induces binding of Stat5A and Stat5B, as well as
      Stat1, to the GAS-like element in the beta-casein promoter. We and others have
      demonstrated previously that specific regions of GHR are required for GH
      dependent activation of what is here identified as Stat5B. To gain insight into
      the mechanism by which GH promotes tyrosyl phosphorylation of Stat5A, GH
      dependent tyrosyl phosphorylation of Stat5A was examined in CHO cells expressing
      truncated and mutated rGHR. The results indicate that Stat5A and Stat5B require
      the same regions of rGHR for maximal activation by GH: the C-terminal half of the
      cytoplasmic domain; tyrosines 333 and/or 338 in the N-terminal half of the
      cytoplasmic domain; and the regions required for JAK2 activation. To dissect
      further the mechanism by which GH activates Stat5A and B, the requirement for
      JAK2 in GH-dependent Stat5 tyrosyl phosphorylation was assessed using JAK2
      deficient cells expressing GHR (gamma2A-GHR) and the wild-type parental cell line
      expressing GHR (2C4-GHR). GH-induced tyrosyl phosphorylation of Stat5B in 2C4-GHR
      cells but not in the JAK2 deficient, gamma2A-GHR cells, indicating that JAK2 is
      required for GH-dependent tyrosyl phosphorylation of Stat5B. Western blotting
      revealed that Stat5A is not expressed in this cell type. Taken together, these
      findings suggest that: 1) GH activates both Stat5A and Stat5B in several cell
      types; 2) the pattern of bands observed differs for Stat5A and Stat5B; 3) GH
      dependent tyrosyl phosphorylation of Stat5A requires specific regions of GHR, and
      these requirements are the same as for Stat5B; and 4) JAK2 kinase is required for
      GH-dependent tyrosyl phosphorylation of Stat5B and, most likely, Stat5A.

PMID- 9231799
TI  - Insulin-degrading enzyme does not require peroxisomal localization for insulin
      degradation.
AB  - Although considerable evidence implicates insulin-degrading enzyme (IDE) in the
      cellular metabolism of insulin in many cell types, its mechanism and site of
      action are not clear. In this study, we have examined the relationship between
      insulin-degrading enzyme's peroxisomal location and its ability to degrade
      insulin by mutation of its peroxisomal targeting signal (PTS), the carboxy
      terminal A/S-K-L tripeptide. Site-directed mutagenesis was used to destroy the
      peroxisomal targeting signal of human insulin-degrading enzyme by changing
      alanine to leucine (AL.pts), leucine to valine (LV.pts), or by deleting the
      entire tripeptide (DEL.pts). The alanine or leucine mutants, when expressed in
      COS cells, were indistinguishable from wild-type insulin-degrading enzyme with
      respect to size (110 kDa), amount of immunoreactive material, ability to bind
      insulin, in vitro activity, and cellular degradation of insulin. In contrast, the
      deletion mutant was shorter in size (approximately 0 kDa) and unable to bind the
      hormone. Thus, although the tripeptide at insulin-degrading enzyme's carboxy
      terminus appeared to confer enzyme stability, the conserved sequence was not
      required for insulin degradation. Finally, an immunocytofluorescence study showed
      that, whereas a significant amount of the wild-type protein was localized in
      peroxisomes, none of the peroxisomal targeting mutants could be detected in these
      organelles. These findings indicate that insulin-degrading enzyme does not
      require peroxisomal localization for insulin degradation and suggest that this
      enzyme has multiple cellular functions.

PMID- 9231800
TI  - Cyclic adenosine monophosphate signaling in the primate corpus luteum:
      maintenance of protein kinase A activity throughout the luteal phase of the
      menstrual cycle.
AB  - Recent studies from our laboratory (Endocrinology 136:4762-4768, 1995)
      demonstrating that the expression of cAMP-dependent nuclear transcription factor
      CREB (cAMP response element binding protein) is lost following ovulation in
      macaques has revealed a novel mechanism by which the cytoplasmic and nuclear
      actions the cAMP-protein kinase A (PKA) intracellular signaling system may be
      regulated independently. Implicit in this hypothesis is the assumption that PKA
      activity is maintained throughout the luteal phase of the menstrual cycle, yet to
      date there have been no published reports regarding PKA activity in the primate
      corpus luteum. PKA activity was assessed by the incorporation of 32P from
      radiolabeled ATP into a PKA-specific peptide substrate (kemptide) in the presence
      or absence of cAMP. Luteal cytosolic fractions were obtained from corpora lutea
      collected during the spontaneous luteal phase (days 3-5, 7-8, 10-11, 13-15, and
      postmenses) or obtained from animals on days 11 or 16 of the luteal phase after
      the animals received seven days of exogenous human CG (hCG) treatment.
      Examination of PKA activity in luteal slices from various aged CL maintained in
      short-term organ culture in the presence or absence of recombinant cynomolgus
      monkey LH was also performed. There were no significant differences in basal or
      cAMP-stimulated PKA activities in corpora lutea collected throughout the
      spontaneous luteal phase. Further, Western immunoblot analyses of the catalytic
      subunit of PKA (PKA C alpha) in corpora lutea collected throughout the luteal
      phase revealed immunoreactive protein bands with similar intensities. In vitro
      addition of recombinant cynomolgus LH and dibutyryl cAMP stimulated PKA activity
      in corpora lutea collected during the early, mid, and late luteal phases. In
      corpora lutea obtained from animals treated with hCG during the midluteal phase,
      basal PKA activity was decreased 65% as compared with untreated day 11 controls
      and in late luteal phase, hCG-exposed CL basal PKA activity was decreased 30% as
      compared with untreated day 16 controls. However, there were no measurable
      differences in cAMP-stimulated PKA activity in CL exposed to prior hCG treatment
      in vivo and Western immunoblot analyses for PKA C alpha in these tissues revealed
      immunoreactive protein bands that were comparable with corpora lutea collected
      from untreated animals. Further, immunoblot analyses for CREB in corpora lutea
      collected from hCG-treated animals revealed that CREB immunoreactivity remained
      undetectable following a treatment regimen with hCG that mimics early pregnancy.
      These results demonstrate that, although CREB expression ceases following
      ovulation, PKA activity is maintained throughout the luteal phase, which provides
      a mechanism by which the acute steroidogenic actions of LH may be separated from
      longer term trophic actions that may rely the transcriptional activity of CREB.

PMID- 9231801
TI  - Phosphoinositolglycan-peptides from yeast potently induce metabolic insulin
      actions in isolated rat adipocytes, cardiomyocytes, and diaphragms.
AB  - Polar headgroups of free glycosyl-phosphatidylinositol (GPI) lipids or protein
      bound GPI membrane anchors have been shown to exhibit insulin-mimetic activity in
      different cell types. However, elucidation of the molecular mode of action of
      these phospho-inositolglycan (PIG) molecules has been hampered by 1) lack of
      knowledge of their exact structure; 2) variable action profiles; and 3) rather
      modest effects. In the present study, these problems were circumvented by
      preparation of PIG-peptides (PIG-P) in sufficient quantity by sequential
      proteolytic (V8 protease) and lipolytic (phosphatidylinositol-specific
      phospholipase C) cleavage of the GPI-anchored plasma membrane protein, Gce1p,
      from the yeast Saccharomyces cerevisiae. The structure of the resulting PIG-P,
      NH2-Tyr-Cys-Asn-ethanolamine-PO4-6(Man1-2)Man1-2Man1-+ ++6Man1-4GlcNH(2)1-6myo
      inositol-1,2-cyclicPO4, was revealed by amino acid analysis and Dionex exchange
      chromatography of fragments generated enzymatically or chemically from the
      neutral glycan core and is in accordance with the known consensus structures of
      yeast GPI anchors. PIG-P stimulated glucose transport and lipogenesis in normal,
      desensitized and receptor-depleted isolated rat adipocytes, increased glycerol-3
      phosphate acyltransferase activity and translocation of the glucose transporter
      isoform 4, and inhibited isoproterenol-induced lipolysis and protein kinase A
      activation in adipocytes. Furthermore, PIG-P was found to stimulate glucose
      transport in isolated rat cardiomyocytes and glycogenesis and glycogen synthase
      in isolated rat diaphragms. The concentration-dependent effects of the PIG-P
      reached 70-90% of the maximal insulin activity with EC50-values of 0.5-5 microM.
      Chemical or enzymic cleavages within the glycan or peptide portion of the PIG-P
      led to decrease or loss of activity. The data demonstrate that PIG-P exhibits a
      potent insulin-mimetic activity which covers a broad spectrum of metabolic
      insulin actions on glucose transport and metabolism.

PMID- 9231802
TI  - Hypothalamic-pituitary-adrenocortical axis changes in a transgenic mouse with
      impaired glucocorticoid receptor function.
AB  - Recently, a transgenic mouse with impaired glucocorticoid receptor (GR) function
      was created to serve as an animal model for the study of neuroendocrine changes
      occurring in stress-related disorders, such as major depression. Here, we
      investigated the hypothalamic-pituitary-adrenocortical (HPA) axis changes in
      these transgenic mice. There were no significant differences between basal early
      morning plasma ACTH and corticosterone levels in normal and transgenic mice. When
      animals were exposed to a mild stressor, an enhanced response in plasma ACTH was
      observed in the transgenic mice, whereas plasma corticosterone responses were not
      different. In view of these differences in plasma ACTH and corticosterone
      responses, we directed our studies toward the regulation of ACTH secretion on the
      hypothalamic-hypophyseal level in vitro. Therefore, an in vitro model, the
      pituitary-hypothalamic complex (PHc) was developed and its ACTH release profile
      was compared with that of the pituitary (PI) alone. The basal ACTH release by PHc
      and PI from normal and transgenic mice was similar. Regardless of the strain
      under study, the basal ACTH release by PI was significantly lower than the
      release by PHc. Stimulation of tissues with either high K+ (56 mM) or CRH (10 or
      20 nM) produced an enhanced ACTH release from both PHc and PI, whereas the
      response in PI was larger than that in PHC. Moreover, the responses to these
      stimuli were markedly enhanced in tissues from transgenic mice. In tissues of
      normal mice, corticosterone inhibited both basal and CRH-stimulated ACTH release
      more potently in PHc than in PI. Furthermore, the feedback capacity of
      corticosterone to restrain both basal and CRH-stimulated ACTH release was highly
      impaired in tissues of transgenic mice, whereas the feedback in PHc appeared to
      be more affected than that in the PI of these animals. In conclusion, the in
      vitro data on PHc and PI revealed intrahypothalamic mechanisms operating 1) to
      fine-tune stimulus-evoked ACTH responses; and 2) to facilitate the negative
      feedback action of glucocorticoids. Moreover, in the transgenic tissues, the
      impaired GR function was found to cause augmented stimulus-evoked ACTH responses
      and an impaired glucocorticoid feedback efficacy which appeared to be mainly
      defective at the hypothalamic level. Thus, in the transgenic mice with life-long
      central GR dysfunction we found impaired negative feedback combined with "normal"
      (i.e. noncompensated) in vivo plasma corticosterone responses. This is a
      condition with potentially grave pathophysiological consequences and, therefore,
      this transgenic animal may be regarded as a valuable model for the study of
      functional glucocorticoid insufficiency at the central nervous system level.

PMID- 9231803
TI  - Characterization of amylin and calcitonin receptor binding in the mouse alpha
      thyroid-stimulating hormone thyrotroph cell line.
AB  - Recently, a high affinity amylin binding site was identified in the mouse alpha
      TSH thyrotroph cell line. In this study, we have characterized binding sites for
      125I-salmon calcitonin (125I-sCT), 125I-rat alpha-calcitonin gene-related peptide
      (125I-CGRP), and 125I-rat amylin in alpha-TSH cells. Using 125I-CGRP or 125I-rat
      amylin, equilibrium was rapidly reached, and binding was fully reversible.
      Competition binding revealed the relative potency of peptides was sCT>amylin,
      CGRP>>rCT, which is similar to the specificity profile of amylin receptors
      characterized in rat brain. Furthermore, specific binding of 125I-rat amylin and
      125I-CGRP to membrane preparations was reduced by 52% and 39%, respectively, in
      the presence of 20 microM GTP-gamma-s, indicating a requirement of G protein
      coupling for high affinity binding. In contrast, 125I-sCT binding reached
      equilibrium more slowly, was essentially irreversible, and was unaltered by GTP
      gamma-s. Competition binding studies using 125I-sCT as radioligand demonstrated
      only weak interaction by CGRP or amylin, consistent with other described CT
      receptors. Assessment of ligand-induced cAMP accumulation and intracellular
      calcium signaling revealed a relative specificity profile of sCT>rCT with little
      or no second messenger signaling stimulated by amylin or CGRP, consistent with a
      C1-CT receptor phenotype. RT-PCR amplification of messenger RNA indicated that
      the predominant isoform was the C1a CT receptor. In cross-linking studies, 125I
      rat amylin and 125I-CGRP specifically labeled a major band of relative molecular
      mass (Mr) approximately 80K, being approximately 10 kDa higher than the major
      125I-sCT binding protein. Full deglycosylation of N-linked carbohydrates with
      endoglycosidase F reduced the Mr of each of the labeled proteins to approximately
      50K. Cross-linked amylin or CT receptors were immunoprecipitated with C
      terminally directed antimouse or antirat CT receptor antibodies but were not
      immunoprecipitated with nonimmune sera or antihuman CT receptor antibodies. The
      current data demonstrate expression of two biochemically distinct receptor
      phenotypes in mouse alpha-TSH cells, a CT receptor phenotype and an amylin
      receptor phenotype that have highly similar protein backbones.

PMID- 9231804
TI  - Pheromone regulated production of inositol-(1, 4, 5)-trisphosphate in the
      mammalian vomeronasal organ.
AB  - Social behaviors of most mammals are profoundly affected by chemical signals,
      pheromones, exchanged between conspecifics. Pheromones interact with dendritic
      microvilli of bipolar neurons in the vomeronasal organ (VNO). To investigate
      vomeronasal signal transduction pathways, microvillar membranes from porcine VNO
      were prepared. Incubation of such membranes from prepubertal females with boar
      seminal fluid or urine results in an increase in production of inositol-(1, 4, 5)
      trisphosphate (IP3). The dose response for IP3 production is biphasic with a GTP
      dependent component at low stimulus concentrations and a nonspecific increase in
      IP3 at higher stimulus concentrations. The GTP-dependent stimulation is mimicked
      by GTPgammaS and blocked by GDPbetaS. Furthermore, the GTP-dependent component of
      the stimulation of IP3 production is sex specific and tissue dependent. Studies
      with monospecific antibodies reveal a G alpha(q/11)-related protein in
      vomeronasal neurons, concentrated at their microvilli. Our observations indicate
      that pheromones in boar secretions act on vomeronasal neurons in the female VNO
      via a receptor mediated, G protein-dependent increase in IP3. These observations
      set the stage for further investigations on the regulation of stimulus-excitation
      coupling in vomeronasal neurons. The pheromone-induced IP3 response also provides
      an assay for future purification of mammalian reproductive pheromones.

PMID- 9231805
TI  - Expression and hormonal regulation of transcription factors GATA-4 and GATA-6 in
      the mouse ovary.
AB  - Two members of the GATA-binding family of transcription factors, GATA-4 and GATA
      6, are expressed in the vertebrate ovary. To gain insight into the role of these
      factors in ovarian cell differentiation and function, we used in situ
      hybridization to determine the patterns of expression of GATA-4 and GATA-6 in
      mouse ovary during development and in response to hormonal stimulation. GATA-4
      messenger RNA (mRNA) was first evident in the ovary around the time of birth. In
      the adult ovary, abundant GATA-4 mRNA was detected in granulosa cells of primary
      and antral follicles, with lesser amounts of GATA-4 message detected in theca
      cells, germinal epithelium, and interstitial cells. Little or no GATA-4 mRNA was
      found in corpus luteum. GATA-6 message exhibited a different distribution in the
      ovary, with abundant expression evident in both granulosa cells and corpora
      lutea. Stimulation of 3-week-old females with PMSG or estrogen enhanced
      follicular expression of GATA-4 and GATA-6 transcripts. Subsequent induction of
      ovulation with human CG resulted in a decrease in GATA-4 mRNA expression in
      granulosa cells, whereas GATA-6 mRNA expression persisted in granulosa cells
      after ovulation and in corpora lutea. Moreover, follicular apoptosis was
      associated with a decrease in the expression of GATA-4 but not GATA-6 message.
      Stimulation of cultured gonadal cell lines with FSH resulted in increased
      expression of GATA-4 message, whereas GATA-6 mRNA expression was not affected. In
      light of these findings, the established role of other GATA-binding proteins in
      hematopoetic cell differentiation and apoptosis, and the presence of conserved
      GATA motifs in the promoters of genes expressed selectively in ovary, we propose
      that GATA-4 and GATA-6 play distinct roles in follicular development and
      luteinization.

PMID- 9231806
TI  - Decreases in cerebral microvasculature with age are associated with the decline
      in growth hormone and insulin-like growth factor 1.
AB  - Several reports have demonstrated that cerebral blood flow decreases with age and
      may contribute to neurodegenerative changes found in aging animals and man.
      Because GH and insulin-like growth factor 1 (IGF-1) decrease with age and have an
      important role in vascular maintenance and remodeling, we hypothesized that the
      decrease in cerebral blood flow is associated with a rarefaction of cerebral
      blood vessels resulting from a decline in GH and IGF-1. Measurements of vascular
      density (number of vessels/cortical surface area) in both Brown-Norway and Fisher
      344/Brown-Norway rats were made at 5, 13, and 29 months of age using chronic
      cranial window chambers that allowed viewing of the cortical surface and its
      corresponding vasculature. Correlations were made with plasma levels of IGF-1. In
      Brown-Norway rats, arteriolar density decreased from 15.53 +/- 1.08 to 9.49 +/-
      0.62 endpoints/mm2 in 7- and 29-month-old animals, respectively (P < 0.05). A
      decline was observed also in arteriolar anastomoses [3.05 +/- 0.21 to 1.42 +/-
      0.24 connections/mm2 in 7- and 29-month-old animals (P < 0.05)]. Venular density
      did not decrease with age. Similar changes were observed in Fisher 344/Brown
      Norway rats. The number of cortical surface arterioles was correlated with plasma
      IGF-1 levels at the time of vascular mapping (r = 0.772, P < 0.05), and injection
      of bovine GH (0.25 mg/kg, s.c., twice daily for 35 days) to 30-month-old animals
      increased both plasma IGF-1 and the number of cortical arterioles. These data
      indicate that: 1) vascular density on the surface of the cortex decreases with
      age; 2) vascular density is correlated with plasma levels of IGF-1; and 3)
      injection of GH increases cortical vascular density in older animals. We conclude
      that GH and IGF-1 have an important role in the decline in vascular density with
      age and suggest that decreases in vascular density may have important
      implications for the age-related decline in cerebral blood flow and brain
      function.

PMID- 9231807
TI  - Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic
      for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion
      gene.
AB  - We have previously developed a transgenic (TG) mouse model expressing the Simian
      virus 40 T-antigen (Tag), driven by a 6-kb fragment of the mouse inhibin alpha
      subunit promoter (inh-alpha). The mice develop metastasizing gonadal tumors, of
      granulosa/theca or Leydig cell origin, with 100% penetrance by the age of 5-8
      months. In the present study, we examined whether the appearance and growth of
      the gonadal tumors are dependent on gonadotropins. Gonadotropin suppression was
      achieved either by treatment of 3-month-old mice for 2-3 months with a GnRH
      antagonist (Cetrorelix, SB-75), or by cross-breeding the TG mice to the genetic
      background of the gonadotropin-deficient hypogonadal mutant mouse (hpg). Gonadal
      tumor growth was clearly inhibited by SB-75 treatment in one of the TG mouse
      lines (IT6-M), as indicated by the absence of macroscopically visible tumors and
      by reduced gonadal weights. Despite the suppressed gonadotropin secretion and Tag
      expression, hyperplasia of testicular Leydig, and ovarian stromal cells persisted
      in some of the treated mice. In another TG mouse line (IT6-F), with more
      aggressive tumorigenesis, the SB-75 treatment only partially inhibited gonadal
      tumor growth. None of the hypogonadotropic TG mice, homozygous for the hpg
      mutation, developed gonadal tumors. Their gonadal histology was indistinguishable
      from that of the non-TG hpg mice, suggesting total inhibition of gonadal
      tumorigenesis in the absence of gonadotropin stimulation. Tag expression and
      Leydig cell hyperplasia were apparent already in the postnatal TG mice but absent
      in those TG mice homozygous for the hpg mutation. In conclusion, the present
      results indicate that the gonadal tumorigenesis in our TG mouse model starts in
      early age as hyperplasia in specific somatic cells. Both this, and the subsequent
      malignant tumor growth, are gonadotropin dependent. A sufficient level of Tag
      expression, a prerequisite for gonadal tumorigenesis, only occurs upon
      gonadotropin stimulation.

PMID- 9231808
TI  - Origin of substrate specificity of human and rat 17beta-hydroxysteroid
      dehydrogenase type 1, using chimeric enzymes and site-directed substitutions.
AB  - Human 17beta-hydroxysteroid dehydrogenase (17-HSD) type 1 predominantly catalyzes
      the 17beta-reduction of estrone to estradiol. The present results, however, show
      that rat 17-HSD type 1 equally uses both estrone and androstenedione as
      substrates. Analyzing the activity of various rat/human chimeric enzymes
      indicated that the region between amino acids 148 and 268 is responsible for the
      difference in substrate specificity, which is in line with the structural data
      showing that the recognition end of the active site is primarily at residues 185
      230. The enzymes are highly conserved between amino acids 148-191, and the data
      indicate that in this region Asn152HisAsp153Glu and Pro187Ala variations are most
      closely related to the differential steroid specificity. The structural analyses
      furthermore suggested that the presence of His instead of Asn at position 152 of
      the human enzyme might result in considerable rearrangement of the loop located
      close to the beta-face of the A- and B-rings of the bound substrate, and that the
      Pro187Ala variation could modify the flexible region involved in substrate
      recognition and access of the substrate to the active site. Altogether, our
      results indicate that the Asn152His and Pro187Ala variations, together with
      several amino acid variations at the recognition end of the catalytic cleft built
      by residues 190-230, alter the structure of the active site of rat 17-HSD type 1
      to one more favorable to an androgenic substrate.

PMID- 9231809
TI  - Elevated luteinizing hormone in prepubertal transgenic mice causes
      hyperandrogenemia, precocious puberty, and substantial ovarian pathology.
AB  - In women, chronically elevated androgens have been associated with polycystic
      ovarian syndrome and infertility. Recently, we described transgenic mice with
      elevated serum LH secondary to targeted expression of a transgene encoding a
      chimeric LH beta-subunit. Mature transgenic females exhibit elevated androgens,
      anovulation, and a range of ovarian phenotypes including cysts, widespread
      luteinization, and tumors. In the present study we have examined serum levels of
      LH and testosterone and the concurrent development of the reproductive system in
      prepubertal mice. Serum LH in prepubertal females was elevated despite increased
      serum testosterone and estradiol, indicating a relative insensitivity to steroid
      negative feedback. Elevated serum LH and hyperandrogenemia resulted in
      accelerated vaginal opening and ovarian follicular development in transgenic
      females. Precocious antral follicle formation and conspicuous hypertrophy of the
      theca-interstitium preceded the development of large cysts with marked
      hemorrhage. Based on these studies we conclude that chronic prepubertal elevation
      of serum LH results in gonadotropin-dependent hyperandrogenemia, leading to
      abnormal sexual development and significant ovarian pathology.

PMID- 9231810
TI  - Expression and characterization of a putative high affinity human soluble leptin
      receptor.
AB  - Leptin, a circulating 16-kDa protein secreted by adipocytes, decreases body
      weight by reducing food intake and enhancing energy utilization. Leptin receptors
      that share homology to the glycoprotein gp130 have been recently cloned. In
      addition, differentially spliced leptin receptor messenger RNAs have been
      identified. Functional mutations in either the leptin or leptin receptor gene
      cause obesity. In the present study, expression of the full length human leptin
      receptor complementary DNA encoding the long cytoplasmic domain of leptin
      receptor in COS7 cells resulted in high affinity membrane binding of 125I-leptin
      (Ki approximately 200 pM); no detectable binding was present in the medium. In
      addition, we expressed the extracellular domain of human leptin receptor in COS7
      cells and identified a soluble leptin receptor in the conditioned medium that
      binds human and mouse leptin with high affinity comparable with the full length
      membrane receptor. Transfected COS7 cells expressing the soluble leptin receptor
      also demonstrated modest specific 125I-leptin binding in whole cells, presumably
      due to association of the soluble leptin receptor to cell membrane proteins. Data
      from cross-linking studies identified two specific bands in the 125I
      leptin/soluble leptin receptor complex with molecular masses of approximately 130
      150 kDa and 300 kDa. The 130-150 kDa molecular mass was confirmed in Western blot
      analysis and Coomassie staining of the purified soluble receptor and probably
      represents the glycosylated form of the receptor. The 300-kDa band most likely
      represents a homodimer of the soluble leptin receptor complex because HPLC gel
      filtration analysis of the 125I-leptin/soluble leptin receptor complex identified
      a single peak corresponding to a molecular mass of approximately 340 kDa. The
      soluble leptin receptor antagonized 125I-leptin binding to the membrane receptor,
      suggesting its potential utility as a functional tool for determining the role of
      endogenous leptin.

PMID- 9231811
TI  - Expression, exon-intron organization, and chromosome mapping of the human sodium
      iodide symporter.
AB  - The active iodide uptake of the thyroid gland in humans is mediated by the human
      sodium iodide symporter (hNIS). In this report, we show that hNIS expression was
      detected primarily in thyroid tissue, but also in breast, colon, and ovary
      tissues. Expression of hNIS is greatly reduced in thyroid tumors compared to
      normal thyroid tissue. Among tumor tissues, hNIS expression appears to be
      variable, consistent with the variable response to radioiodide treatment observed
      for thyroid carcinomas. The coding region of hNIS is interrupted by 14 introns,
      and the nucleotide sequence of each exon-intron junction is reported. Using this
      information, an alternatively spliced form of hNIS was identified. Finally, the
      chromosome location of the hNIS gene was mapped to chromosome 19p.

PMID- 9231812
TI  - A constitutively active version of the Ser/Thr kinase Akt induces production of
      the ob gene product, leptin, in 3T3-L1 adipocytes.
AB  - The expression of the ob gene product leptin in adipose tissues has been
      previously described to be regulated by insulin in vivo and vitro. Akt, a ser/thr
      kinase with a pleckstrin homology domain, has recently been identified to
      function in the insulin receptor signaling cascade. The aim of this study was to
      investigate the role of Akt in the production of leptin by adipocytes. Therefore,
      we examined leptin production by 3T3-L1 adipocytes stably expressing a
      myristoylated version of Akt which is constitutively active. Leptin levels in the
      supernatants of serum starved, nonstimulated 3T3-L1 adipocytes were determined by
      radioimmunoassay (RIA). Expression of the constitutively active Akt was found to
      induce a more than 20-fold increase in leptin levels whereas a control non
      myristoylated Akt had no effect. Leptin mRNA levels as determined by either RNase
      protection assay or reverse transcriptase (RT)-polymerase chain reaction (PCR)
      were not elevated by the constitutively active Akt. These results indicate that
      Akt can induce leptin production in 3T3-L1 adipocytes via a non-transcriptional
      mechanism.

PMID- 9231813
TI  - Ambulatory and home blood pressure normality in the elderly: data from the PAMELA
      population.
AB  - To determine ambulatory blood pressure (BP) means and distributions in an elderly
      population, we studied a random sample of 800 subjects stratified by sex and
      representative of residents aged 65 to 74 years of the city of Monza.
      Participation was 50%. Measurements consisted of clinic BP (average of three
      measurements with mercury sphygmomanometry), home BP (average of morning and
      evening measurements with a semiautomatic device), and ambulatory BP (SpaceLabs
      90207). Clinic BP was obtained before and after home and ambulatory BP
      measurements. In normotensive and untreated hypertensive subjects (n=248),
      clinic, home, and ambulatory BPs were significantly related (P<.001). The means
      of the clinic BPs obtained on consecutive days were very similar and markedly
      higher than 24-hour average BP (+25 mm Hg systolic and + 10 mm Hg diastolic,
      P<.001). Nighttime BP was markedly less than daytime BP (-14 and -13 mm Hg,
      P<.001), whereas home BP values occurred approximately midway between clinic and
      24-hour average BP values. Only minor differences existed between data in men and
      women, and the differences in clinic, home, and ambulatory BP values occurred in
      both normotensive and untreated hypertensive subjects. All BPs were similar in
      the untreated and treated hypertensive groups. Thus, as previously reported in
      subjects younger than 65 years, in the elderly fraction of the population, 24
      hour average BP is much lower than clinic BP. The upper limit of normality for 24
      hour average BP (calculated as the value corresponding to 140/90 mm Hg clinic BP)
      is about 120 mm Hg systolic and 76 mm Hg diastolic. At variance with data from
      younger subjects, home BP in the elderly is higher than 24-hour average BP.
      However, similar to data from younger subjects, clinic, home, and ambulatory BPs
      are higher in treated hypertensive than normotensive elderly subjects, indicating
      that in hypertensive elderly subjects, antihypertensive treatment does not
      commonly achieve full BP control both inside and outside the clinic environment.

PMID- 9231814
TI  - Safety of nifedipine in patients with hypertension: a meta-analysis.
AB  - Our objective was to compare cardiovascular event rates in patients with mild or
      moderate hypertension who received nifedipine with active drug controls. We
      performed a MEDLARS search using the MeSH heading "hypertension" and the text
      word "nifedipine" to identify all articles that were published between 1966 and
      August 1995 in English, French, German, Italian, and Spanish languages and that
      involved human subjects. The computerized search was supplemented by a manual
      search of article bibliographies. Review of 1880 citations revealed 98 randomized
      controlled clinical trials that met protocol criteria. Articles were extracted
      independently by two doctors who were blinded for author, institution, and
      treatment regimen, using a structured, pretested extraction form. Differences of
      opinion were resolved by consensus. Fourteen events occurred in 5198 exposures
      (0.27%) to nifedipine and 24 events in 5402 exposures (0.44%) to other active
      drug controls. Unadjusted odds ratios for nifedipine versus controls were 0.49
      (95% confidence interval [CI], 0.22-1.09) for definitive events (death, nonfatal
      myocardial infarction or stroke, revascularization procedure) and 0.61 (95% CI,
      0.31-1.17) for all events (definitive plus increased angina). The odds ratio for
      nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was
      nonsignificantly higher for definitive and all events (odds ratio, 1.40; 95% CI,
      0.49-4.03 and odds ratio, 1.39; 95% CI, 0.59-3.32, respectively). The odds ratio
      for nifedipine in combination with another drug was significantly lower for
      definitive and all events (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio,
      0.15; 95% CI, 0.03-0.65, respectively). Differences in odds ratio for nifedipine
      monotherapy and combined therapy were statistically significant (P=.02 for
      definitive events and P=.001 for all events). Results support the safety of
      sustained- and extended-release nifedipine in the treatment of mild or moderate
      hypertension when it is used in combination with other drugs.

PMID- 9231815
TI  - Endothelin-1-induced vasopressor responses in essential hypertension.
AB  - The potential role of endothelin-1 (ET-1) in essential hypertension in humans is
      still subject to debate. We recently reported strong sodium retention and renal
      vasoconstriction during pathophysiological increments in plasma ET-1. Apart from
      this vasoconstrictor action, ET-1 also has mitogenic properties that play a role
      in the pathophysiology of hypertension. On the other hand, some data refute an
      important role of ET-1 in hypertension. We therefore investigated in nine
      subjects with essential hypertension the constrictor actions of ET-1 by
      challenging these subjects with a systemic infusion of ET-1 (0.5 ng/kg per minute
      for 60 minutes, then 1.0 ng/kg per minute for 60 minutes, and finally 2.0 ng/kg
      per minute for 60 minutes). Furthermore, we studied whether these effects of ET-1
      could be modulated by oral use of the angiotensin-converting enzyme inhibitor
      enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD). ET-1
      infusion increased plasma ET-1 levels from 2.5+/-0.4 to 11.6+/-1.0 pmol/L
      (P<.05). Blood pressure rose by approximately 10 mm Hg (P<.05). Cardiac index
      decreased by 21+/-22%, whereas calculated systemic vascular resistance increased
      by 27+/-6% (P<.05). Renal blood flow decreased from 1051+/-94 to 707+/-60 mL/min
      at the end of the ET-1 infusion (P<.05), and calculated renal vascular resistance
      increased from 118+/-19 to 189+/-19 mm Hg x min/L (P<.05). Sodium excretion
      decreased from 227+/-39 to 111+/-15 micromol/min (P<.05). Both enalapril and
      nifedipine treatment prevented the systemic effects of ET-1 infusion in these
      subjects. However, during enalapril treatment, despite renal predilatation, ET-1
      reduced renal blood flow (from 1119+/-132 to 701+/-75 mL/min, P<.05) and
      increased renal vascular resistance (from 111+/-16 to 187+/-28 mm Hg x min/L,
      P<.05) to the same levels as during ET-1 infusion alone. Nifedipine pretreatment
      attenuated the ET-1-induced fall in renal blood flow (from 1088+/-93 to 907+/-68
      mL/min) and increase in renal vascular resistance (from 105+/-9 to 133+/-10 mm Hg
      x min/L). Although neither drug modulated the antinatriuretic effect of ET-1,
      nifedipine increased basal sodium excretion (P<.05), which compensated for the
      decrease during ET-1 infusion. In conclusion, essential hypertensive subjects are
      sensitive to the vasoconstrictor effects of ET-1. Both enalapril and nifedipine
      can prevent the systemic effects of ET-1, but nifedipine seems more effective in
      attenuating the renal constrictor effects of ET-1.

PMID- 9231816
TI  - Endogenous endothelin modulates blood pressure, plasma volume, and albumin escape
      after systemic nitric oxide blockade.
AB  - To assess whether acute nitric oxide (NO) blockade could unmask the vascular
      actions of endogenous endothelin, we tested the effects of the endothelin type
      A/type B (ET(A)/ET(B)) receptor antagonist bosentan and the selective ET(A)
      antagonist FR 139317 on blood pressure, plasma volume, and albumin escape after
      inhibition of NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME).
      Conscious, chronically catheterized rats received L-NAME in the absence and
      presence of 17.4 micromol/kg (10 mg/kg) bosentan or 3.8 micromol/kg (2.5 mg/kg
      I.V., 10 minutes before L-NAME) FR 139317. Red blood cell volume and plasma
      volume were determined with chromium-51-tagged erythrocytes and iodine-125
      labeled albumin, respectively. L-NAME (0.46 to 7.42 micromol/kg [0.125 to 2
      mg/kg]) induced a dose-dependent increase in blood pressure, which was attenuated
      by 60% and 48% with bosentan and FR 139317, respectively (P<.01). L-NAME (7.42
      micromol/kg) also increased hematocrit. This effect was associated with an
      increase in total-body albumin escape, which is reflected by a 14% reduction in
      plasma volume. Red blood cell volume remained unchanged. L-NAME promoted albumin
      escape primarily in the lung, heart, liver, kidney, and gastrointestinal tract.
      Both bosentan and FR 139317 markedly reduced these effects of L-NAME.
      Furthermore, L-NAME increased plasma levels of immunoreactive endothelin-1 from
      8.6+/-0.4 (n=10) to 14.7+/-1.4 pg/mL (n=9, P<.01). These results demonstrate that
      the pressor response, losses in plasma volume, and increase in albumin escape
      observed after inhibition of NO synthesis are in part the consequence of
      unmasking the actions of endogenous endothelin, which are mediated predominantly
      via ET(A) receptors. These findings suggest a role for endogenous endothelin in
      the regulation of vascular functions in conditions when NO formation by
      endothelial cells is impaired.

PMID- 9231818
TI  - Regulation of vascular type 1 angiotensin receptors by cytokines.
AB  - Although various cytokines are known to be expressed in atherosclerotic lesions,
      it is not known how these cytokines affect receptors for the peptide hormone
      angiotensin II (Ang II). We therefore examined the effects of interleukin-1 alpha
      (220 U/mL [10 ng/mL]), tumor necrosis factor-alpha (280 U/mL [100 ng/mL]), and
      interferon gamma (100 U/mL) on Ang II type 1 (AT1) receptors expressed in rat
      vascular smooth muscle cells. Treatment with interleukin-1 alpha caused a 1.4- to
      1.7-fold increase in AT1 binding after 24 hours (P<.01) and a 2.3-fold increase
      in AT1 mRNA (P<.05). Tumor necrosis factor-alpha and interferon gamma did not
      cause a significant change in AT1 binding when administered alone but caused a
      30% reduction in binding when administered together (P<.05). The maximal decrease
      in AT1 binding (60%, P<.01) was seen with the combination of interleukin-1 alpha
      with tumor necrosis factor-alpha and interferon gamma. Although the upregulation
      of AT1 by interleukin-1 alpha was unaffected by pretreatment of cells with N
      monomethyl-L-arginine or indomethacin, downregulation of AT1 by interleukin-1
      alpha combined with tumor necrosis factor-alpha/interferon gamma was inhibited by
      N-monomethyl-L-arginine (P<.01). Interleukin-1 alpha treatment enhanced Ang II
      induced [3H]uridine incorporation, whereas treatment with interleukin-1 alpha
      combined with tumor necrosis factor-alpha/interferon gamma attenuated Ang II
      induced [3H]uridine and [3H]leucine incorporation. These results demonstrate that
      interleukin-1 alpha upregulates AT1 receptors and enhances Ang II-stimulated
      hypertrophic responses. However, a combination of interleukin-1 alpha with tumor
      necrosis factor-alpha and interferon gamma downregulates AT1 receptors by a
      nitric oxide-dependent mechanism and reduces Ang II-stimulated trophic responses
      in vascular smooth muscle cells.

PMID- 9231817
TI  - Role for endothelin-1 in angiotensin II-mediated hypertension.
AB  - Experiments in cultured vascular smooth muscle cells have shown that angiotensin
      II (Ang II) stimulates expression of endothelin-1. We sought to examine role of
      endothelin-1 in the effects of Ang II in vivo. Ang II infusion in rats (0.7 mg/kg
      per day for 5 days) was associated with marked increases in vascular smooth
      muscle endothelin-1 levels, as assessed by immunostaining. Administration of the
      selective endothelin type A (ET(A)) receptor antagonist PD 155080 (50 mg/kg per
      day) abrogated the hypertensive response to a 5-day infusion of Ang II (0.7 mg/kg
      per day), as did losartan (25 mg/kg per day). ET(A) receptor blockade during Ang
      II-mediated hypertension was associated with marked elevations of plasma
      endothelin-1 levels. Ang II-mediated hypertension was associated with heightened
      vascular responsiveness to a variety of vasoconstrictor agents except endothelin
      1. Blockade of ET(A) receptor invariably corrected this vasoconstrictor
      hyperresponsiveness. We conclude that some of the vascular effects of Ang II
      thought to be unique to this hormone are likely mediated by endothelin-1.

PMID- 9231819
TI  - Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in
      tissues and its intracellular half-life in vivo.
AB  - Angiotensin II (Ang II) is internalized by various cell types via receptor
      mediated endocytosis. Little is known about the kinetics of this process in the
      whole animal and about the half-life of intact Ang II after its internalization.
      We measured the levels of 125I-Ang II and 125I-Ang I that were reached in various
      tissues and blood plasma during infusions of these peptides into the left cardiac
      ventricle of pigs. Steady-state concentrations of 125I-Ang II in skeletal muscle,
      heart, kidney, and adrenal were 8% to 41%, 64% to 150%, 340% to 550%, and 680% to
      2100%, respectively, of the 125I-Ang II concentration in arterial blood plasma
      (ranges of six experiments). The tissue concentrations of 125I-Ang I were less
      than 5% of the arterial plasma concentrations. 125I-Ang II accumulation seen in
      heart, kidney, and adrenal was almost completely blocked by a specific Ang II
      type 1 (AT1) receptor antagonist. Steady-state concentrations of 125I-Ang II were
      reached within 30 to 60 minutes in the tissues and within 5 minutes in blood
      plasma. The in vivo half-life of intact 125I-Ang II in heart, kidney, and adrenal
      was approximately 15 minutes, compared with 0.5 minute in the circulation. Thus,
      Ang II, but not Ang I, from the circulation is accumulated by some tissues, and
      this is mediated by AT1 receptors. The time course of this process and the long
      half-life of the accumulated Ang II support the contention that this Ang II has
      been internalized after its binding to the AT1 receptor, so that it is protected
      from rapid degradation by endothelial peptidases. The results of this study are
      in agreement with growing evidence of an important physiological role for
      internalized Ang II.

PMID- 9231820
TI  - Basal release of nitric oxide is decreased in the coronary circulation in
      patients with heart failure.
AB  - It is unknown whether basal release of endothelium-derived nitric oxide in the
      coronary artery is altered in heart failure in humans. The aim of the present
      study was to evaluate the effect of inhibition of nitric oxide synthesis on basal
      tone of the conduit and resistance coronary arteries in awake patients. Coronary
      blood flow velocity (Doppler guide wire) and coronary arterial diameter
      (quantitative coronary angiography) were measured in 14 patients with heart
      failure caused by nonischemic left ventricular dysfunction (7 idiopathic dilated
      cardiomyopathy and 7 valvular insufficiency) and 7 patients with normal
      ventricular function (controls). Intracoronary N(G)-monomethyl-L-arginine (L
      NMMA), an inhibitor of nitric oxide synthesis, at graded doses decreased coronary
      blood flow in both groups. However, the magnitude of flow reduction was smaller
      in patients with heart failure than in control patients (P<.0001). The magnitude
      of coronary blood flow reduction in response to L-NMMA inversely correlated to
      indexes of left ventricular contractile function (P<.01) but was not affected by
      the cause of heart failure. Constriction of the large epicardial coronary artery
      with L-NMMA also tended to be attenuated in patients with heart failure. In
      summary, vasoconstricting response to L-NMMA was blunted in the coronary
      resistance artery in heart failure in vivo. These findings suggest that basal
      release of nitric oxide in the coronary circulation is decreased in patients with
      heart failure.

PMID- 9231821
TI  - Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator
      function in hypercholesterolemic but not in hypertensive patients.
AB  - Hypercholesterolemic and hypertensive patients have impaired endothelium
      dependent vasorelaxation because of decreased nitric oxide activity, but the
      mechanism underlying this abnormality is unknown. This study sought to determine
      whether an increased breakdown of nitric oxide by xanthine oxidase-generated
      superoxide anions could participate in these forms of endothelial dysfunction. We
      studied vascular responses to intrabrachial infusion of acetylcholine (an
      endothelium-dependent vasodilator, 7.5 to 30 microg/min) and sodium nitroprusside
      (a direct smooth muscle dilator, 0.8 to 3.2 microg/min) by strain-gauge
      plethysmography before and during the combined administration of oxypurinol (300
      microg/min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patients,
      20 essential hypertensive patients, and 20 normal subjects. The vasodilator
      response to acetylcholine was blunted in hypercholesterolemic (highest flow,
      8.2+/-8 mL x min(-1) x dL(-1)) and hypertensive (8.5+/-4 mL x min(-1) x dL(-1))
      patients compared with control subjects (13.8+/- 6.6 mL x min(-1) x dL(-1)) (both
      P<.001); however, no differences were observed in the response to sodium
      nitroprusside. Oxypurinol did not change the response to acetylcholine in control
      subjects (P=.26) and improved, but did not normalize, its vasodilator effect in
      hypercholesterolemic patients (P<.01). Oxypurinol did not affect the response to
      acetylcholine in hypertensive patients (P=.34) and did not modify the response to
      sodium nitroprusside in any group. These results suggest that xanthine oxidase
      generated superoxide anions are partly responsible for the impaired endothelial
      vasodilator function of hypercholesterolemic patients. In contrast, this
      mechanism does not appear to play a significant role in essential hypertension.

PMID- 9231822
TI  - The sympathetic nervous system is involved in the maintenance but not initiation
      of the hypertension induced by N(omega)-nitro-L-arginine methyl ester.
AB  - Studies in anesthetized animals have advanced the theory that there is an
      important neurogenic component to the hypertension caused by pharmacological
      inhibition of nitric oxide, but studies in conscious animals have produced
      conflicting evidence for and against this theory. To try to reconcile the
      seemingly contradictory data, we hypothesized that the neurogenic component of
      this hypertension is time dependent such that the sympathetic nervous system is
      involved primarily in the maintenance, rather than the initiation, of the
      hypertension. We measured intra-arterial pressure in conscious, unrestrained rats
      with and without guanethidine-induced sympathectomy during varying durations of
      intravenous N(omega)-nitro-L-arginine methyl ester (L-NAME). The major new
      finding is that sympathectomy had no effect on the hypertensive response to bolus
      injections of L-NAME but in the same rats it produced a greater than 50%
      attenuation in the hypertension seen after 6 days of continuous L-NAME (change in
      mean arterial pressure, 23+/-4 versus 55+/-4 mm Hg, P<.01, sympathectomy versus
      control). Using 8-hour infusions of L-NAME, we found that 60 minutes was the
      minimum time required for detecting a sympathectomy-sensitive component of L-NAME
      induced hypertension. Furthermore, we demonstrate that the magnitude of this
      component increases further between 8 hours to 6 days of continuous L-NAME: it
      accounted for only 18% of the total hypertensive response at 8 hours but 61%
      after 6 days. From these experiments, we conclude that the importance of the
      sympathetic system in the pathogenesis of L-NAME-induced hypertension accrues
      slowly over hours and days, and thus its importance can be overlooked by focusing
      on the initial phase of the hypertension.

PMID- 9231824
TI  - Neurovascular compression of the rostral ventrolateral medulla related to
      essential hypertension.
AB  - The rostral ventrolateral medulla (RVLM) is thought to serve as a final common
      pathway for the integration of central cardiovascular information and to be
      important for the mediation of central pressor responses. An association between
      essential hypertension and neurovascular compression of the RVLM has been
      reported. To confirm this relationship and to quantitatively measure the
      distances between the RVLM and the neighboring arteries, we performed magnetic
      resonance imaging using a high-resolution 512x512 matrix and magnetic resonance
      angiography in 49 subjects (21 patients with essential hypertension, 10 patients
      with secondary hypertension, and 18 normotensive subjects). One patient with
      essential hypertension was excluded from the evaluations because of inadequate
      assessment due to poor images. Neurovascular compression of the RVLM was observed
      in 15 of 20 (75%) patients with essential hypertension. In contrast,
      neurovascular compression was observed in only 1 of 10 (10%) patients with
      secondary hypertension and only 2 of 18 (11%) normotensive subjects. The rate of
      observed neurovascular compression in the essential hypertension group was
      significantly higher than that in the secondary hypertension group and the
      normotensive group (P<.01 for both). The distances between the RVLM and the
      nearest arteries in the essential hypertension group were significantly shorter
      than those in the other groups (P<.05 for all). On the other hand, the distances
      between the surface of the medulla oblongata and the nearest arteries did not
      differ among these three groups. These results suggest that neurovascular
      compression of the RVLM, but not of the other regions of the medulla oblongata,
      is particularly related to essential hypertension.

PMID- 9231823
TI  - Plasma epinephrine and norepinephrine concentrations of healthy humans associated
      with nighttime sleep and morning arousal.
AB  - We assessed the activity of the sympathetic nervous system during undisturbed
      nocturnal sleep and periods of wakefulness directly before and after sleep in
      healthy young men. Changes induced by periods of rapid eye movement and by
      morning awakening, both periods reported to demonstrate an enhanced risk for the
      onset of cardiovascular diseases, were of particular interest. In 13 healthy men
      (age, 18 to 35 years), blood for determination of epinephrine and norepinephrine
      was drawn every 7 minutes between 9:30 PM and 8:30 AM with the subjects resting
      in a strictly horizontal position. Lights were switched off at 11 PM until
      awakening at 7 AM. At 8:30 AM, subjects stood up and a final blood sample was
      drawn. Sleep was monitored somnopolygraphically, and heart rate and blood
      pressure were continuously measured. Average epinephrine but not norepinephrine
      concentrations were significantly lower during nocturnal sleep than during
      wakefulness before and after sleep. In parallel, heart rate and blood pressure
      declined significantly during sleep. During rapid eye movement sleep, both
      epinephrine and norepinephrine concentrations were significantly lower than
      during sleep stages 1 and 2 and slow-wave sleep. Whereas epinephrine
      concentrations gradually began to increase after morning awakening,
      norepinephrine levels were not significantly enhanced. However, standing up at
      the end of the experiment sharply increased norepinephrine concentrations by
      180%, whereas epinephrine levels were less enhanced (46%) by the change of body
      position. This study suggests that the decrease in the activity of the
      sympathoadrenal branch of the sympathetic nervous system is probably due to an
      entrainment to the sleep-wake cycle, whereas the low activity of the
      noradrenergic branches depends mainly on horizontal body position during
      nocturnal sleep. The activities of the sympathoadrenal and noradrenergic branches
      of the sympathetic nervous system seem to be downregulated during rapid eye
      movement sleep. Awakening itself selectively enhances epinephrine levels.
      Subsequent orthostasis activates both the sympathoadrenal and, most prominently,
      the noradrenergic branches of the sympathetic nervous system.

PMID- 9231825
TI  - Clonidine and ST-91 may activate imidazoline binding sites in the heart to
      release atrial natriuretic peptide.
AB  - It is well established that the antihypertensive drug clonidine acts through
      specific imidazoline receptors in the brain and kidney to increase diuresis,
      natriuresis, and kaliuresis. We have previously shown that the effects of
      clonidine are associated with elevated plasma atrial natriuretic peptide (ANP).
      Similar to clonidine, ST-91, a clonidine analogue that does not cross the blood
      brain barrier, evokes renal responses that are also associated with elevated
      plasma ANP. The mechanisms of ANP increase elicited by these imidazoline drugs
      are unclear. Since ANP is primarily released from the cardiac atria, we
      investigated the direct effect of the imidazoline drugs on ANP release by
      incubating left and right atrial sections with 10(-6) mol/L ST-91 in the presence
      and absence of efaroxan, a selective imidazoline I1 receptor antagonist, for 30
      minutes at 37 degrees C. ST-91 significantly stimulated ANP release, and the
      effect was inhibited by 10(-6) mol/L efaroxan. Further studies using heart
      perfusion with the imidazoline drugs with and without antagonists over 30 minutes
      revealed that both clonidine and ST-91 gradually stimulated ANP release. Also,
      perfusion with these compounds resulted in a gradual decrease in heart rate, but
      bradycardia was significant only with clonidine. The effects of ST-91 were
      inhibited by 10(-6) mol/L efaroxan and to a lesser extent by 10(-6) mol/L
      yohimbine, implying that the actions of ST-91 were mainly mediated by I1
      receptors. On the other hand, the actions of clonidine were inhibited by 10(-5)
      mol/L efaroxan and by 10(-6) mol/L yohimbine, an alpha2-adrenoceptor antagonist,
      which may suggest that the actions of clonidine were preferentially mediated by
      alpha2-adrenoceptors in the heart. These results indicate that the peripheral
      actions of clonidine are probably mediated by alpha2 and imidazoline receptors
      and may involve direct stimulation of ANP release by the cardiac atria--an effect
      that may account for the increase in plasma ANP levels and diuresis and
      natriuresis observed in vivo after administration of clonidine and its analogues.

PMID- 9231826
TI  - Endogenous retroviral transcripts in myocytes from spontaneously hypertensive
      rats.
AB  - The spontaneously hypertensive rat (SHR) is a well studied animal model of
      genetic hypertension and heart disease of unknown cause. With the use of
      differential display, a transcript was found in SHR myocardium that on sequence
      analysis was identified as an endogenous retrovirus (ERV). ERV gene expression
      was greater than an order of magnitude increased in adult SHR hearts relative to
      age-matched normotensive Wistar-Kyoto rats and was further increased in hearts
      from SHR with heart failure. In situ hybridization studies demonstrated that
      increased ERV gene expression was localized to myocardial cells. Increases in ERV
      transcripts in SHR suggest a possible link between inherited proviral elements
      and genetic hypertensive heart disease.

PMID- 9231827
TI  - Elevation of ouabainlike compound levels with hypertonic sodium chloride load in
      rat plasma and tissues.
AB  - A major biologically active endogenous digitalis-like factor in the mammalian
      body may be an isomer of ouabain (ouabainlike compound, OLC). However, the exact
      role of OLC in sodium homeostasis is still unclear, and acute isotonic volume
      expansion does not enhance the secretion of OLC. We tested the hypothesis that
      OLC may be more important in the response to acute hypertonic NaCl load rather
      than isotonic volume expansion. We injected intraperitoneally 2 mL of 20% NaCl
      solution into male Wistar rats (n=34) and measured OLC levels in plasma,
      hypothalamus, pituitary, and adrenal at baseline (n=10) and 1, 2, and 4 hours
      (n=8 for each). In response to hypertonic NaCl loading, plasma Na-K ratio was
      elevated at 2 and 4 hours (P<.01). OLC levels in pituitary increased (P<.01) at 1
      hour. Thereafter, plasma OLC levels increased at 2 and 4 hours (P<.05; basal,
      75+/-11 pmol/L [+/-SEM]; 1 hour, 55+/-11; 2 hours, 130+/-24; 4 hours, 156+/-20).
      Concomitantly, OLC levels in adrenal increased at 2 and 4 hours (P<.01; basal,
      1.7+/-0.2 pmol/g; 1 hour, 4.5+/-0.9; 2 hours, 5.0+/-0.7; 4 hours, 6.8+/-2.2). A
      significant correlation was observed between OLC levels in plasma and adrenal
      (P<.05). Plasma Na-K ratio positively correlated with OLC levels in plasma
      (r=.51, P<.01) and adrenal (r=.48, P<.01). Similar injection of physiological
      saline solution or hypertonic sucrose solution in physiological saline did not
      increase OLC levels in plasma and tissues. These findings indicate the elevation
      of OLC levels in plasma, pituitary, and adrenal in response to acute hypertonic
      NaCl load in rats and suggest that OLC may be involved in the response to the
      hypernatremic state.

PMID- 9231828
TI  - Erythrocyte sodium-lithium countertransport in non-modulating offspring and
      essential hypertensive individuals: response to enalapril.
AB  - Non-modulators are a subset of essential hypertensive individuals in whom renal
      hemodynamic and adrenal aldosterone responses to angiotensin II fail to modulate
      appropriately during high dietary salt intake. The main aim of this study was to
      investigate the familial aggregation of non-modulation and several erythrocyte
      Na+ transport systems in normotensive and hypertensive individuals as well as
      offspring of hypertensive parents. An additional aim was to evaluate the effect
      of treatment with enalapril on erythrocyte Na+ transport. We studied 15
      normotensive subjects (6 males, 27+/-6 years), 14 untreated modulating essential
      hypertensive subjects (7 males, 38+/-7 years), 12 untreated non-modulating
      essential hypertensive subjects (7 males, 38+/-6 years), 14 modulating offspring
      of hypertensive parents (8 males, 25+/-6 years), and 14 non-modulating offspring
      of hypertensive parents (8 males, 26+/-4 years). Blood pressure was recorded with
      an oscillometric device and renal plasma flow and glomerular filtration rate by
      clearances of para-aminohippurate and inulin, respectively. Non-modulating
      subjects were identified as individuals who failed to increase effective renal
      plasma flow by 30% and decrease filtration fraction by at least 30% 10 days after
      changing from a low (20 mmol/d) to a high (250 mmol/d) sodium intake. Erythrocyte
      Na+ transport was characterized by measurements of the Na+-K+ pump, Na+-Li+
      countertransport, Na+-K+-Cl- cotransport, passive Na+ permeability, and Na+
      content. After the initial studies, hypertensive individuals were treated with
      enalapril (20 mg/d P.O.) for 6 months, after which erythrocyte Na+ transport
      measurements were again made. The main findings were that Na+-Li+
      countertransport is increased in non-modulating hypertensive subjects and non
      modulating offspring of hypertensive parents, that the increase in blood pressure
      in response to high salt intake is greater in non-modulating than modulating
      hypertensive subjects, and that enalapril decreases Na+-Li+ countertransport
      activity to normal in non-modulating hypertensive subjects. These findings
      provide support for a possible genetic role in the development of salt
      sensitivity and suggest that Na+-Li+ countertransport and non-modulation are
      related phenotypes.

PMID- 9231829
TI  - Induction of mitogen-activated protein kinase phosphatase-1 during acute
      hypertension.
AB  - Recently, we demonstrated that elevated blood pressure activates mitogen
      activated protein (MAP) kinases in rat aorta. Here we provide evidence that the
      vascular response to acute hypertension also includes induction of MAP kinase
      phosphatase-1 (MKP-1), which has been shown to function in the dephosphorylation
      and inactivation of MAP kinases. Restraint or immobilization stress, which leads
      to a rapid rise in blood pressure, resulted in a rapid and transient induction of
      MKP-1 mRNA followed by elevated MKP-1 protein expression in rat aorta. That the
      induction of MKP-1 by restraint was due to the rise in blood pressure was
      supported by the finding that several different hypertensive agents
      (phenylephrine, vasopressin, and angiotensin II) were likewise capable of
      eliciting the response, and sodium nitroprusside, a nonspecific vasodilator agent
      that prevented the acute rise in blood pressure in response to the hypertensive
      agents, abrogated MKP-1 mRNA induction. The in vivo effects could not be mimicked
      by treatment of cultured aortic smooth muscle cells with similar doses of the
      hypertensive agents. These findings support a role for MKP-1 in the in vivo
      regulation of MAP kinase activity during hemodynamic stress.

PMID- 9231830
TI  - Mechanosensitive cation channels in aortic endothelium of normotensive and
      hypertensive rats.
AB  - In response to humoral and hemodynamic stimuli, vascular endothelium regulates
      vascular tone by releasing endothelium-derived vasoactive factors. Stretch
      activated cation channels have been postulated to act as endothelial
      mechanosensors that respond to changes in hemodynamic forces. We report the
      presence of a nonselective (n=98) and K+-selective (n=53) stretch-activated
      channel in rat intact aortic endothelium and isolated aortic endothelial cells.
      The nonselective channel showed a permeability ratio for Na+, K+, and Ca2+ of
      1:0.95:0.23 and was completely blocked by 50 micromol/L gadolinium, a blocker of
      stretch-activated channels. The K+-selective channel was selectively permeable
      for K+, with a K+-Na+ permeability ratio of 10.9:1. In whole-cell current
      recordings, hyposmotic cell swelling induced an increase in cell conductance. The
      swelling-induced current was completely blocked by 50 micromol/L gadolinium,
      showing that stretch-activated channels were activated by cell swelling and carry
      macroscopic cell currents. In a comparative study with normotensive Wistar-Kyoto
      rats (WKY) and spontaneously hypertensive rats (SHR), the K+-selective stretch
      activated channel was observed in a 4.4-fold higher density in adult SHR compared
      with WKY. Also, in adult SHR, the stretch sensitivity of the nonselective channel
      was nearly twice as high as in WKY. In contrast, channel properties were
      unchanged in young SHR (5 to 6 weeks old) compared with age-matched WKY. These
      data suggest that stretch-activated channels are regulated in their sensitivity
      and density when subjected to increased hemodynamic forces such as in
      hypertension. Since the channels are capable of acting as endothelial
      mechanosensors, the altered channel properties might contribute to an altered
      mechanoreception in hypertension.

PMID- 9231831
TI  - Reversal of microvascular rarefaction and reduced renal mass hypertension.
AB  - This study examined the microcirculatory and renin-angiotensin system changes
      following the reversal of hypertension in reduced renal mass rats. Nine-week-old
      Sprague-Dawley reduced renal mass rats were placed on a low or high sodium diet
      for 4 or 8 weeks or a combination of 4 weeks of high sodium followed by 4 weeks
      of low sodium. Blood pressure was directly measured during the development of
      hypertension and its reversal. Plasma renin activity, angiotensin-converting
      enzyme activity, and angiotensin II concentrations were measured throughout the
      experiment. The cremaster and hindlimb muscles were removed, and microvascular
      density was determined by quantitative stereology. Four weeks of high sodium
      increased blood pressure (152+/-7 mm Hg) and reduced microvessel density (13.7%).
      Reduced renal mass hypertension was rapidly reversed after the rats were returned
      to a low sodium diet (124+/-7 mm Hg after 3 days), and microvascular density
      returned to control levels. After 4 weeks of high sodium, circulating plasma
      renin activity and angiotensin II fell by 94% and 82%, respectively. Plasma
      angiotensin-converting enzyme activity was increased after 2 weeks of high sodium
      but returned to control levels after 4 weeks of high sodium. This study
      demonstrates that microvascular density is reduced in reduced renal mass
      hypertensive rats following exposure to high sodium diet and this is associated
      with a fall in circulating plasma renin activity and angiotensin II levels.
      Microvascular density can return to normal levels after a reactivation of the
      circulating renin-angiotensin system. This study provides further evidence for
      the hypothesis that modulation of the renin-angiotensin system is important in
      the regulation of microvascular structure.

PMID- 9231832
TI  - Blood pressures and cardiovascular homeostasis in mice having reduced or absent
      angiotensin-converting enzyme gene function.
AB  - We studied cardiovascular phenotypes in wild-type (+/+), heterozygous (+/-), and
      homozygous mutant (-/-) mice for an insertional inactivation of the angiotensin
      converting enzyme (ACE) gene (Ace in mice, ACE in humans). Compared with +/+
      mice, baseline mean arterial pressure was not significantly altered in +/- mice
      but was reduced by 51+/-4 mm Hg in -/- mice. Although the pressor response to
      injected angiotensin II did not differ significantly in the three genotypic
      groups, the pressor response to angiotensin I was strongly affected by Ace
      genotype: Compared with the response in the +/+ group (+26% of baseline), the
      response to Ang I was close to half normal (+12%) in the +/- group and virtually
      abolished (+1%) in the -/- group. The depressor response to injected bradykinin
      was significantly enhanced in the +/- and -/- groups compared with the +/+ group.
      Ace expression and ACE activity were directly related to functional Ace copy
      number, and renin and angiotensinogen mRNA levels were inversely related to Ace
      copy number. Angiotensin type 1A receptor mRNA levels were not significantly
      different in the +/+, +/-, and -/- groups. We conclude that (1) ACE is essential
      for the maintenance of normal blood pressure; (2) subnormal levels of ACE affect
      the blood pressure responses to infused angiotensin I and bradykinin in vivo; and
      (3) compensations for inactivation of one Ace copy, which include increased
      expression of renin, normalize blood pressure in heterozygotes.

PMID- 9231833
TI  - Increased transforming growth factor-beta production and gene expression by
      peripheral blood monocytes of hypertensive patients.
AB  - Cultured human peripheral blood monocytes are known to secrete and express
      transforming growth factor-beta (TGF-beta), a multifunctional cytokine that can
      be involved in myocardial and vascular remodeling. In addition,
      monocytes/macrophages have been demonstrated to be colocalized with fibrosis of
      hypertrophied heart and in the vascular wall of hypertensive vessels. In this
      study, we tested TGF-beta production and mRNA expression in peripheral blood
      monocytes from hypertensive patients with myocardial hypertrophy and increased
      carotid myointimal thickness with respect to healthy normotensive control
      subjects. We found an increased TGF-beta activity in the conditioned medium of
      monocytes from hypertensive patients compared with control subjects as evaluated
      by inhibition of [3H]thymidine incorporation by mink lung epithelial cells (-83%
      and -18% in hypertensive and normotensive subjects; P<.001). Western blot
      analysis confirmed a significant difference in the amount of TGF-beta protein
      secreted in the conditioned medium of hypertensive patients compared with that of
      normotensive subjects. Finally, we also observed a 4.2- and 5.5-fold increase in
      the amount of TGF-beta1 and TGF-beta2 transcripts, respectively. Our results
      indicate an upregulation of the TGF-beta system in the peripheral blood monocytes
      of hypertensive patients with cardiovascular structural changes, suggesting a
      possible role of TGF-beta monocyte production in hypertensive disease.

PMID- 9231834
TI  - Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a
      multicenter placebo-controlled trial. Treatment in Obese Patients With
      Hypertension (TROPHY) Study Group.
AB  - Because obesity-associated hypertension has unique hemodynamic and hormonal
      profiles, certain classes of antihypertensive agents may be more effective than
      others as monotherapy. Thus, we compared the efficacy and safety of the
      angiotensin-converting enzyme inhibitor lisinopril and the diuretic
      hydrochlorothiazide in a 12-week, multicenter, double-blind trial in 232 obese
      patients with hypertension. Patients with an office diastolic pressure between 90
      and 109 mm Hg were randomized to treatment with daily doses of lisinopril (10,
      20, or 40 mg), hydrochlorothiazide (12.5, 25, or 50 mg), or placebo. Mean body
      mass indexes were similar for all patients. At week 12, lisinopril and
      hydrochlorothiazide effectively lowered office diastolic (-8.3 and -7.7 versus 
      3.3 mm Hg, respectively; P<.005) and systolic (-9.2 and -10.0 versus -4.6 mm Hg,
      respectively; P<.05) pressures compared with placebo. Ambulatory blood pressure
      monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered
      24-hour blood pressure compared with placebo (P<.001). Significant dose-response
      differences were observed between treatments. Sixty percent of patients treated
      with lisinopril had an office diastolic pressure <90 mm Hg compared with 43% of
      patients treated with hydrochlorothiazide (P<.05). Responses to therapies
      differed with both race and age. Neither treatment significantly affected insulin
      or lipid profiles; however, plasma glucose increased significantly after 12 weeks
      of hydrochlorothiazide therapy compared with lisinopril (+0.31 versus -0.21
      mmol/L; P<.001). Hydrochlorothiazide also decreased serum potassium levels by 0.4
      mmol/L from baseline. In conclusion, lisinopril was as effective as
      hydrochlorothiazide in treating obese patients with hypertension. Treatment with
      angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy
      at lower doses compared with thiazide diuretics, may have a more rapid rate of
      response, and may offer advantages in patients at high risk of metabolic
      disorders.

PMID- 9231835
TI  - Roles of systolic and pulse pressures.

PMID- 9231836
TI  - Serum haptoglobin and ferritin during a competitive running and swimming season.
AB  - The purpose of the study was to examine ferritin, haptoglobin, and red cell
      indices during a competitive running and swimming season. Male runners (N = 8)
      and swimmers (N = 5) were tested four times during their respective seasons. The
      runners were tested before the start of organized practice (RT1), after 3 wk of
      increased training (RT2), 3 wk prior to the conference championship (pre-taper,
      RT3), and 3 d after the conference championship (post-taper, RT4). The swimmers
      were tested after the first 9 wk of training (ST1), after completing 2 wk of hard
      training (ST2), after an additional 6wk of training (pre-taper, ST3), and 1 wk
      following the conference championship (post-taper, ST4). For the runners,
      hemoglobin, hematocrit, and red blood cell number were lower (p < 0.05) at RT2
      and were not accompanied by significant changes in other red cell indices or
      haptoglobin. Serum ferritin in the runners was lower at RT3 and RT4 compared to
      RT1 despite an adequate dietary iron intake. Hemoglobin and mean cell hemoglobin
      concentration were lower and mean cell volume was higher in the swimmers at ST3
      and ST4. No significant changes were observed in other red cell indices for
      swimmers; however, serum haptoglobin tended (p = 0.07) to be reduced at ST2. In
      conclusion, collegiate male runners and swimmers do not demonstrate clinical
      hypoferritinemia, hypohaptoglobinemia, or alterations in red cell indices
      suggestive of the early stage of anemia with or without iron deficiency during
      their respective season.

PMID- 9231837
TI  - Plasma insulin-like growth factor-I and high affinity growth hormone-binding
      protein levels increase after two weeks of strenuous physical training.
AB  - The high affinity growth hormone-binding protein (GHBP) circulates in human blood
      and represents the extracellular domain of the growth hormone (GH) receptor. It
      is well known that repetitive bouts of endurance type exercise result in
      increased integrated GH secretion. As the effects of chronic exercise on plasma
      GHBP levels have never been studied systematically, we investigated the effect of
      2 weeks of intense endurance training on plasma GHBP as well as on plasma insulin
      like growth factor (IGF)-I levels in 10 healthy, young, non-obese men. IGF-I was
      measured as an indicator of the effects of GH release. We also studied 10 control
      subjects matched for sex, age and activity, who were instructed not to change
      their customary activities. GHBP was determined by FPLC size exclusion
      chromatography and subsequent Scatchard plot analysis of the binding data; IGF-I
      levels were measured by RIA. The results showed that plasma IGF-I and GHBP levels
      were increased in the subjects who followed the training program. IGF-I and GHBP
      changed from 252 +/- 56 ng/ml and 912 +/- 59 pmol/l before training, to 344 +/-
      61 ng/ml (p < 0.01) and 1020 +/- 48 pmol/l (p < 0.01), respectively. Another
      effect of the training was that the aerobic capacity of these subjects was better
      utilized and endurance was improved. In contrast, plasma IGF-I, GHBP, utilization
      of aerobic capacity and endurance did not change significantly in the control
      subjects. We conclude that two weeks of strenuous endurance training lead to
      increased plasma IGF-I and high affinity GHBP levels.

PMID- 9231839
TI  - The acute effects of exercise on bone turnover.
AB  - Exercise is known to have long-term benefits on bone mass, but little is known
      about the short-term effects of exercise on bone turnover. The purpose of this
      study was to investigate whether acute effects of exercise on bone remodelling
      could be detected by measuring blood and urinary markers of bone turnover. We
      measured biochemical markers of bone turnover in ten healthy, young men before
      and up to 32 hours after 30 minutes of brisk treadmill walking. Blood samples
      were taken before, immediately after and at 0.5, 1, 8, 24 and 32 hours after the
      exercise. These were assayed for osteocalcin and bone specific alkaline
      phosphatase. Twenty-four hour urine samples were taken over three days (day
      before, day of and day after exercise) and measured for pyridinoline and
      deoxypyridinoline crosslinks. Crosslink excretion was standardised for total body
      bone mineral content (TBBMC) and urinary creatinine. Total body bone mineral
      density (and content) and body composition were measured by dual energy X-ray
      absorptiometry. No changes in the levels of either osteocalcin or alkaline
      phosphatase were seen at any time point following the exercise. Both urinary
      crosslinks exhibited an increase in levels on the day of the exercise and a
      further significant increase the day after (pyridinoline 38.7%, p = 0.05;
      deoxypyridinoline 42.3%, p = 0.025; median, corrected for TBBMC). There were
      significant negative correlations between the crosslinks, osteocalcin and body
      fat percentage. In conclusion, the exercise appears to have stimulated bone
      resorption within 32 hours of moderate exercise, but there was no measurable
      effect on bone formation after 32 hours. A longer study period may be necessary
      to detect changes in bone formation.

PMID- 9231838
TI  - Resistance training in the treatment of non-insulin-dependent diabetes mellitus.
AB  - Aerobic endurance exercise has traditionally been advocated in the treatment of
      non-insulin-dependent diabetes mellitus (NIDDM). However, the effect of aerobic
      endurance exercise programs on long-term glycaemic control is small to moderate.
      The aim of the present study was to determine the effect of circuit resistance
      training on long-term glycaemic control (HbA1c) and to examine the potential
      association between muscle size and glycaemic control in NIDDM subjects. Eight
      NIDDM subjects participated in a 3 month individualized progressive resistance
      training program (moderate intensity, high-volume) twice a week with measurements
      of HbA1c, lipids, blood pressure, VO2max and thigh muscle cross-sectional area.
      There was a significant improvement in HbA1c (8.8% - 8.2%; p < 0.05). Muscle
      endurance increased by 32 +/- 23% (p < 0.05), and the cross-sectional area of m.
      vastus lateralis increased by 21% (p < 0.001). There was a strong inverse
      correlation between HbA1c and muscle cross-sectional area (knee extensors) after
      the exercise period (r = -0.73; p < 0.05). Circuit resistance training seems to
      be feasible in moderately obese, sedentary elderly NIDDM subjects and the
      inclusion of circuit resistance training in exercise training programs for NIDDM
      subjects should be considered.

PMID- 9231840
TI  - Effects of a 110 kilometers ultra-marathon race on plasma hormone levels.
AB  - To assess changes of sex hormones, cortisol, prolactin (PRL) and beta-endorphins
      in an exhaustive aerobic performance, blood samples were taken in 11 endurance
      trained runners (R) along an ultra-marathon race of 110 km (T1 before the start,
      T2 at km 33, T3 at km 75 and T4 immediately after completing the race). Results
      were compared to a control group (C) who followed the race. Cortisol (p < 0.001)
      and beta-endorphins (p = 0.009) showed a significant increase during the race
      without significant modification after T2. Testosterone decreased along the race
      (p = 0.02). Luteinising hormone (LH) was lower at the end of the race as compared
      to the start in the R. No modification of PRL was noticed in the runners. Most of
      the modifications except for testosterone were observed from the start to T2,
      even in exhaustive performance no further modification was noticed from that
      point onwards.

PMID- 9231841
TI  - Growth hormone and insulin-like growth factor I responses to moderate submaximal
      acute physical exercise in man: effects of octreotide, a somatostatin analogue,
      administration.
AB  - We evaluated growth hormone (GH) and insulin-like growth factor I (IGF-I)
      response to moderate submaximal acute short-term physical exercise under basal
      conditions and after the administration of octreotide, a somatostatin analogue
      (SA), in a double-blind, counter-balanced experimental protocol. Seven untrained
      male volunteers performed two identical exercise tests, each on a treadmill (2.5%
      slope) for 30 minutes (min) at 60% of VO2max. Before starting the exercise test
      all the subjects received a single administration of placebo or octreotide and
      vice versa at two different sessions. Plasma GH, IGF-I and lactate assays were
      evaluated before starting, during, at the end and in the recovery phase. In the
      placebo-treated group GH rose significantly both during exercise and recovery
      whereas no significant modifications in IGF-I levels were observed. SA
      administration inhibited the exercise-dependent GH secretion, which showed a
      small rise only during exercise and returned to basal levels during recovery. In
      the same group, IGF-I decreased significantly after exercise compared to basal
      values. The results suggest that 1) in our experimental conditions acute physical
      exercise at aerobic threshold does not modify IGF-I concentration 2) SA is able
      to inhibit the exercise-dependent GH secretion and to decrease post-exercise IGF
      I concentration.

PMID- 9231842
TI  - Dynamics of respiratory response to sinusoidal work load in humans.
AB  - The present study was undertaken to investigate possible distortion in responses
      of respiratory variables including O2 uptake (VO2), CO2 output (VCO2), and
      ventilation (VE) to sinusoidal work load, and to find out whether the
      conventional transfer models were applicable to analyze the dynamics of these
      variables. Six healthy subjects performed exercise for 32 min on a bicycle
      ergometer with electro-magnetic braking. The work load was varied sinusoidally
      between 30 W and 60% of maximum O2 uptake (VO2max) during periods from 1 to 16
      min. The respiratory variables were measured on a breath-by-breath basis with a
      mass spectrometer and a computer system. The responses of VO2, VCO2, and VE to
      sinusoidal work load were not completely sinusoidal in form but were somewhat
      distorted, forming saw-tooth waves with steeper down-slopes during periods of 4
      16 min, but this distortion was not observed at 1 min or 2 min periods. However,
      the results could be approximately described by a first-order model without or
      with time delay. Time constants of the first-order model without time delay were
      46 sec for VO2, 62 sec for VCO2, and 73 sec for VE, respectively. We also found a
      close relationship between the time constants of VO2 and VCO2 and VO2max. These
      results suggested that exponential functions may be applied and are expected to
      yield valid results in assessing physical fitness, although the control of
      ventilatory and gas exchange in exercise does show non-linear characteristics.

PMID- 9231844
TI  - Economy during a simulated laboratory test triathlon is highly related to Olympic
      distance triathlon.
AB  - This study examined the relationship between Olympic distance triathlon (swim
      over 1.5 km, cycle over 40.0 km, and run over 10.0 km) and economy during a
      simulated laboratory test triathlon. Seventeen male triathletes conducted both
      maximal exercise tests and simulated laboratory triathlon. The latter test
      consisted of swimming (S), cycling (C) and running (R) stages as a continuous
      task using a flume-pool, a cycle ergometer and a treadmill, respectively. The
      exercise intensity and duration were 60% of VO2max during swimming, cycling and
      running for 30, 75 and 45 min, respectively. The index of economy was determined
      by the % VO2max at the last min of each stage during a simulated laboratory test
      triathlon. Results indicated that Olympic distance triathlon (total time) was
      correlated to swimming-VO2max (r = -0.621, p < 0.001), cycling-VO2max (r = 
      0.873, p < 0.001), running-VO2max (r = -0.891, p < 0.001), S-Economy (r = 0.208,
      ns), C-Economy (r = 0.601, p < 0.001) and R-Economy (r = 0.769, p < 0.001). There
      were also significant correlations between swimming time and swimming-VO2max (r =
      -0.648, p < 0.01), between cycling time and cycling-VO2max (r = -0.819, p
      <0.001), between running time and running-VO2max (r = -0.726, p < 0.001), between
      swimming time and S-Economy (r = 0.550, p < 0.05), between cycling time and C
      Economy (r = 0.613, p < 0.01), and between running time and R-Economy (r = 0.548,
      p < 0.05). These results demonstrated that the larger VO2max during maximal
      exercise tests and smaller increment of VO2 during a simulated laboratory test
      triathlon indicating good economy were good predictors to determine the Olympic
      distance triathlon.

PMID- 9231843
TI  - Changes in plasma tryptophan/branched chain amino acid ratio in responses to
      training volume variation.
AB  - The major symptoms of overtraining including decreased exercise performance,
      altered mood states, and depleted muscle glycogen stores closely resemble the
      effects of brain serotonin, the level of which is dependent on the plasma ratio
      of tryptophan to branched-chain amino acids (BCAA). To examine the relation
      between plasma amino acids and overtraining, ten highly-trained endurance runners
      underwent two weeks of base training (normal training) before increasing their
      training volume by 40% for two weeks to achieve a state of short-term
      overtraining (or overreaching). The overtraining period was followed by two weeks
      of recovery in which training volume was reduced by 41% of the base training. For
      the whole group, no significant changes were observed in running economy and
      maximum oxygen uptake. There were no changes in resting heart rate, blood
      pressure, resting metabolic rate, and serum cortisol level in response to the
      changes in training volume. The runners experienced a significant increase (p <
      0.05) in fatigue score for the profile of mood states when the training volume
      was increased. The elevated fatigue score returned to baseline when the training
      volume was reduced. Plasma free or total tryptophan, BCAA, and the
      tryptophan/BCAA ratio were not significantly altered throughout the course of
      this study. We concluded that proposed physiological markers of overtraining,
      including plasma tryptophan and BCAA levels, were unchanged despite a 40%
      increase in training volume.

PMID- 9231845
TI  - Is the Olympic boardsailor an endurance athlete?
AB  - The present study was carried out in order to describe the physiological profile
      of top Olympic boa rdsailors of both genders and to measure the energy cost
      during actual boardsailing with particular attention to the most demanding
      conditions. Fourteen elite Olympic boardsailors (7 males and 7 females)
      volunteered to participate in the study. Each subject underwent a maximal cycle
      ergometer test in orderto measure VO2peak and ventilatory threshold (Tvent).
      Additionally, anthropometric measurements including body fat percentage were
      taken. The cardiorespiratory demand and the energy cost of actual boardsailing
      were assessed by means of a very light telemetric device (K2 Cosmed) which
      allowed the measurements of VO2, VE and HR. VO2peak was 63.6 +/- 2.3 ml x kg(-1)
      x min(-1) (Tvent 70% of maximum) and 49.2 +/- 4.1 (Tvent 60% of maximum) in males
      and females, respectively. The data recorded during actual boardsailing show that
      this sport activity can be classified as aerobic, the VO2 values being above or
      very close to those of Tvent values (75% and 60% of the maximum in males and
      females). Furthermore the mean blood lactate values obtained at the end of each
      regatta testing were 6 +/- 2 mMol x l(-1) in males and 5 +/- 1.5 mMol x l(-1) in
      females indicating a partial involvement of anaerobic metabolism, which in some
      regatta phases could represent a limiting factor for performance.

PMID- 9231846
TI  - The prognosis of ankle sprains.
AB  - We developed a new diagnostic tool for predicting the severity of ankle sprains
      just after injury. Since hard data obtained by diagnostic imaging techniques are
      still imperfect, we decided to use data from individual medical history and signs
      and symptoms that are part of the admission routine. During a three month-period
      data were collected on thirty-five patients with lateral ankle sprains who
      visited the first aid department of the University Hospital of Maastricht.
      Assessments took place at admission and at two and four weeks after injury.
      Assessors were the first-aid physician, a physiotherapist and the patient.
      Dependent variables were healed ankle in two and four weeks. Predicting variables
      were the data obtained at admission by the physician, the physiotherapist and the
      patient. The ability to predict outcome after two and four weeks was determined
      in a bivariate analysis, followed by logistic modelling. Accurate prediction of
      recovery time at admission appeared to be possible. Best two weeks predictor was
      the modified function score, an accuracy of 97% was achieved. Four weeks
      prediction was most accurate when function score was used together with the
      report mark from the doctor and the palpation score (accuracy of 81%).

PMID- 9231847
TI  - Knee flexion to extension peak torque ratios and low-back injuries in highly
      active individuals.
AB  - The purpose of this study was to investigate for possible relationships between
      knee flexion to extension peak torque ratios (F1/Ext(rat)) and low-back injuries
      in highly active males and females. Forty-eight male (age 25.9 +/- 4.5 years) and
      41 female (age 27.3 +/- 2.6 years) competitive rowers, and 20 male (age 26.6 +/-
      6.0 years) professional ballet dancers volunteered for the study. Each subject
      performed a test of lumbar and knee flexor flexibility, isokinetic dynamometry
      and completed a self-administered questionnaire. Flexibility was assessed by
      using the sit-and-reach test. Knee flexion to extension peak torques were
      bilaterally monitored at the angular velocities of 1.04 and 4.19 rad x s(-1). The
      questionnaire was designed to obtain information regarding the number of days off
      action (e.g., training, competition, and rehearsals), due to low-back injuries,
      for the 12-month period prior to testing. Results revealed significant negative
      correlation coefficients between knee F1/Ext(rat), obtained at 1.04 rad x s(-1),
      and days off physical activity for oarsmen (r = - 0.69; p < 0.01), oarswomen (r =
      -0.62; p < 0.01) and male dancers (r = -0.57; p < 0.05). No such correlations
      were found for either knee F1/ Ext(rat) obtained at the angular velocity of 4.19
      rad x s(-1) or between the sit-and-reach test results and low-back injuries. A
      sub-group of 22 female rowers was re-tested after a 6-8 month period, during
      which a special hamstring strength training programme was introduced. The main
      conclusions were: a) the lower the F1/Ext(rat) the greater the degree of low-back
      injury, b) at least in female rowers, 6-8 months of hamstring strength training
      can contribute to a reduction of the incidence of low-back injury, and c)
      isokinetic assessment of quadriceps and hamstrings obtained at lower compared to
      higher angular velocities is more prognostic of low back injury.

PMID- 9231848
TI  - Reduced ultrasound velocity in tibial bone of young ballet dancers.
AB  - Young ballet dancers are at risk both for osteopenia, due to low body weight,
      inadequate nutrition and gonadal dysfunction, as well as for lower limbs stress
      fractures. However, a direct relationship between stress fractures and bone mass
      in dancers could not be demonstrated, raising the possibility that qualitative
      aspects of bone, such as elasticity, may be adversely affected in the dancers. To
      test this hypothesis, speed of sound, a physical parameter that reflects both
      quantitative and qualitative properties of bone, was determined at the tibial
      bone of 27 dance students and 27 non-dance students. The results were compared to
      bone mineral density at the tibia and the lumbar spine, measured by dual-energy x
      ray absorptiometry. All three bone measurements were lower in the dance group,
      but the difference was statistically significant only for the tibial speed of
      sound. The role of tibial speed of sound measurement in assessing bone status in
      athletes warrants further exploration.

PMID- 9231849
TI  - Endurance running performance in relation to cardiovascular risk indicators in
      adolescents.
AB  - We evaluated endurance running performance and body mass index (BMI) in relation
      to biochemical cardiovascular disease (CVD) risk indicators (s-lipids, s-insulin,
      s-ferritin), and blood pressure in 14- and 17-year-old healthy Swedish
      adolescents (n = 879), also considering current dietary intake and physical
      activity. Endurance running performance was assessed using a 3 km running test
      and height, body weight, waist and hip circumference, and skinfolds were measured
      at clinical examination. Physical activity and dietary intake were evaluated
      using self-reported 7-day-records. The results showed that high endurance running
      performance was related to a favourable CVD risk indicator profile. Multiple
      regression analyses including running time, BMI, physical activity, dietary fat
      and iron intake, and age as independent and s-lipids, s-insulin, and s-ferritin
      as dependent variables revealed that, in both boys and girls, low BMI was
      associated to a favourable s-lipid profile and lower s-insulin values and, in
      boys but not in girls, also to lower s-ferritin values. There were, however, no
      independent associations between level of physical activity or endurance running
      performance on the one side and s-lipids, s-insulin, or s-ferritin values on the
      other. High dietary fat intake was associated to s-lipids in a non-atherogenic
      direction; in boys to higher HDL-C and in girls to lower TG. In conclusion the
      study showed that body mass seems to be the most important factor explaining the
      differences in s-lipid and s-insulin values between adolescents with different
      level of physical performance capacity. An interesting finding was, that s
      ferritin, being a proposed risk factor for CVD, in the older boys related to body
      mass in a similar way as s-lipids and s-insulin.

PMID- 9231851
TI  - How should multiple organ dysfunction syndrome be assessed? A review of the
      variations in current scoring systems.
AB  - There are many scores for evaluating multiple organ dysfunction (MODS) which
      differ appreciably, and this makes it difficult to compare results from different
      research groups. In addition the variables used to describe organ dysfunction are
      not always as organ-specific as they should be. In this review we have studied 20
      MODS scoring systems to illustrate the variety in variables used to assess organ
      dysfunction.

PMID- 9231850
TI  - Four years of practice-based and exercise-supported behavioural medicine in one
      community of the German CINDI area. Countrywide Integrated Non-Communicable
      Diseases Intervention.
AB  - The main goal of the preventive intervention study in one community of the German
      CINDI (Countrywide Integrated Non-Communicable Diseases Intervention programme of
      the WHO) area was to improve cardiovascular health by reducing the risk factors
      smoking, hypertension, obesity, hypercholesterolaemia, and by changing sedentary
      lifestyle. The intervention was performed by using the special "Three-Level
      Strategy", which is characterised by activities of primary care physicians in the
      usual consulting hour (1st level), with patient groups in their practices (2nd
      level), and at community level (3rd level) where a special work group and a co
      ordinating general practice are co-operating. To evaluate the occurrence of the
      risk factors in practice and the local population, four cross-sectional random
      samples (N(total) = 4881) were carried out in seven practices from 1992 to 1995.
      On the community level, 23 special exercise-based health groups (N(total) = 600)
      were established and were investigated by means of a questionnaire, related to
      behaviour and health beliefs. A "Local Health Information System" facilitated the
      evaluation, the management of the data, and the organisation of the health
      programme. The results of the practice samples showed a significant reduction of
      smoking (-17.8%) and hypertension (-31.5%) (p < 0.01). The exercise-based groups
      were combined with nutritional counselling or relaxation and were accepted very
      well by the participants (83.8%). The participants considerably improved their
      health behaviour: 82% discussed health in their family, 37.3% stated an increase
      of healthy nutrition, 52% of relaxation; 86.2% intended to regularly increase
      physical activity in leisure time and 82 % could not imagine regular health
      training without exercise meetings. We conclude that the practice-based "Three
      Level-Strategy" provides a strong support for successful long-term prevention of
      cardiovascular risk, particularly, when exercise-based health training sessions
      are performed in order to change sedentary lifestyle. When organised on community
      level, they might have a positive impact on the health behaviour of the whole
      community. Physical activity can be used as a "prodrug" for health promotion in a
      holistic way.

PMID- 9231852
TI  - Successful management of eleven splanchnic artery aneurysms.
AB  - OBJECTIVE: To describe our experience with the management of aneurysms of the
      splanchnic arteries. DESIGN: Retrospective study. SETTING: Teaching hospital,
      Norway. SUBJECTS: Eleven consecutive patients with aneurysms of the splanchnic
      arteries treated between 1986 and 1996, six of them between 1994 and 1996. Four
      aneurysms were hepatic (37%), two splenic (18%), one coeliac (9%), one
      gastroepiploic (9%), one pancreaticoduodenal (9%), one superior mesenteric (9%),
      and one jejunal (9%). Five were pseudoaneurysms (46%). INTERVENTIONS: Six
      patients (55%) were treated by operation, four (36%) by embolisation and one (9%)
      expectantly. RESULTS: The pathogenesis was inflammatory (acute pancreatitis,
      anastomotic leak) in four patients (36%), athero-sclerotic in three (27%),
      arterial infusion of cytotoxic drugs in one (9%), and unknown in four (36%).
      Seven patients (64%) presented with rupture, two (18%) with other symptoms, and
      two patients (18%) were diagnosed incidentally. There was no mortality.
      CONCLUSION: There may be an increased incidence in splanchnic artery aneurysms,
      particularly those created by inflammatory lesions. The diagnosis should be
      suspected if acute bleeding occurs during the course of severe intra-abdominal
      inflammation. Arteriography should be used to diagnose an aneurysm in
      haemodynamically stable patients. Control of bleeding is obtained either by
      transarterial catheter embolisation or by operation.

PMID- 9231853
TI  - Curative resection in potentially resectable tumours of the gallbladder.
AB  - OBJECTIVE: To study the value of surgical treatment in patients with potentially
      resectable gallbladder cancer. DESIGN: Prospective non-randomised study. SETTING:
      University hospital, Chile. SUBJECTS: 109 Patients with gallbladder cancers, most
      of which were detected in the cholecystectomy specimen. INTERVENTIONS: 53
      Patients underwent reoperation with the aim of doing a lymphadenectomy and
      resecting the gallbladder bed. MAIN OUTCOME MEASURES: Morbidity and short and
      long term mortality RESULTS: Residual tumour after cholecystectomy was mainly
      observed in patients with serosal and adipose tissue infiltration. Lymph nodes
      and liver invasion were associated with recurrence. Survival analysis was focused
      on the group with subserosal infiltration because it is the largest subgroup in
      this study and prognosis is intermediate. Patients who underwent curative
      resection had a significantly better survival than those treated by simple
      cholecystectomy (p = 0.005). CONCLUSIONS: Extended cholecystectomy improved the
      prognosis of patients whose cancers were restricted to the subserosal layer.
      Additional treatments are necessary to improve the results obtained with
      operation alone.

PMID- 9231854
TI  - Estimating the probability of acute appendicitis using clinical criteria of a
      structured record sheet: the physician against the computer.
AB  - OBJECTIVE: To evaluate physicians' probability estimates of acute appendicitis
      based on structured collection of clinical data. DESIGN: Open prospective study.
      SETTING: District hospital, Norway. SUBJECTS: 304 patients admitted with
      suspected acute appendicitis. INTERVENTIONS: Initial diagnostic accuracy of
      physicians was compared with corresponding results from a computer model. MAIN
      OUTCOME MEASURES: The estimated probabilities of appendicitis in different
      testing groups were analysed using receiver operating characteristic (ROC)
      curves. RESULTS: Physicians' estimates had a mean area under ROC-curve of 0.81
      (95% CI 0.79 to 0.82), not significantly different from the computer model. Both
      correlated well with the actual rate of appendicitis, but the physicians tended
      to overestimate the probability by 10%. CONCLUSION: Physicians' probability
      estimates perform rather well. Further attempts to implement a probabilistic
      approach in the diagnostic process of acute appendicitis therefore seem
      justified.

PMID- 9231855
TI  - Comparison of clinical judgment and diagnostic ultrasonography in the diagnosis
      of acute appendicitis: experience with a score-aided diagnosis.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of clinical judgment and
      diagnostic ultrasonography (US) used routinely and to create a scoring system to
      aid diagnosis. DESIGN: Prospective, double-blind study. SETTING: University
      hospital, Denmark. SUBJECTS: 222 Consecutive patients suspected of having acute
      appendicitis admitted between 0800 and midnight from June 1990 to June 1992.
      INTERVENTIONS: 148 Patients (67%) underwent appendicectomy and the remaining 74
      patients were observed. 193 Patients (87%) had a diagnostic US examination. 21
      Predictive variables were collected prospectively to create a scoring system.
      MAIN OUTCOME MEASURES: Results of surgical pathological findings, clinical
      outcome (observed group), diagnostic US, and values of diagnostic score. RESULTS:
      The decision to operate was made by a junior surgeon solely on the clinical
      examination, which yielded a diagnostic accuracy of 76%, specificity of 58%, and
      negative appendicectomy rate of 36%. 193 Patients underwent diagnostic US
      conducted by the radiologist on call of whom 123 were operated on, 78 for
      histologically proven appendicitis. US had a diagnostic accuracy of 72%,
      sensitivity of 49%, and specificity of 88%. Of the 21 predictive factors for
      acute appendicitis 11 were significant (p < 0.05): total white cell count (WCC)
      (>10 x 10[9]/1), migration of pain to the right lower quadrant, gradual onset of
      pain, increasing intensity of pain, pain aggravated by movement, pain aggravated
      by coughing, anorexia, vomiting, indirect tenderness (Rovsing's sign), muscle
      spasm, and sex. These 11 predictors were assigned an appropriate weight, based on
      the likelihood ratio, and used to create a scoring system. The score performed
      poorly if it was used to separate patients for observation and those for
      appendicectomy. However, if the score was used with two cut-off points resulting
      in three test zones (low, intermediate, and high risk of having acute
      appendicitis), some diagnostic benefit was seen for those patients within the
      zones of high and low probability. CONCLUSION: The clinical judgment of a junior
      surgeon was disappointing, and diagnostic aids are desirable to reduce the
      negative appendicectomy rate. Diagnostic US performed poorly as a routine
      procedure. Application of an up to date scoring system might be of some help to
      patients with a high or low probability of acute appendicitis, but any conclusion
      about its clinical application cannot be drawn from this study.

PMID- 9231856
TI  - Comparison of polyglycolic acid and polypropylene mesh for rectopexy in the
      treatment of rectal prolapse.
AB  - OBJECTIVE: To compare the efficacy of absorbable and non-absorbable mesh for
      rectal fixation in abdominal rectopexy. DESIGN: Prospective open study. SETTING:
      University hospital, Israel. SUBJECTS: 37 consecutive patients with complete
      rectal prolapse. INTERVENTIONS: Posterior abdominal rectopexy with non-absorbable
      mesh (Polypropylene, Prolene, Ethicon Ltd) in 17 patients and with absorbable
      mesh (Polyglycolic acid, Dexon, Davis & Geck) in 20. MAIN OUTCOME MEASURES: There
      was no operative mortality, and there were no significant differences between the
      groups in the incidence of postoperative complications. Mean (SD) follow up was
      3.6(0.5) years and 3.8(0.7) years in the Dexon and Prolene groups, respectively.
      Preoperative and postoperative performance indices based on the Gastrointestinal
      Quality of Life Index were similar in both groups. CONCLUSIONS: Dexon mesh may be
      as effective as Prolene mesh in the treatment of complete rectal prolapse. A
      performance index seems to be a useful tool for evaluating the outcome of
      patients after repair of complete rectal prolapse.

PMID- 9231857
TI  - Catalytic activity of phospholipase A2 in serum in experimental fat embolism in
      pigs.
AB  - OBJECTIVE: To investigate the catalytic activity of phospholipase A2 in serum
      during the early phase of experimental fat embolism. DESIGN: Randomised
      controlled experimental study. SETTING: Animal laboratory, Finland. SUBJECTS: 18
      domestic pigs weighing 25-31 kg. INTERVENTIONS: Allogeneic bone marrow suspension
      at a dose of 100 mg/kg was infused intracavally in 9 anaesthetised, mechanically
      ventilated, and haemodynamically monitored pigs; 9 control pigs received saline.
      MAIN OUTCOME MEASURES: Central haemodynamics, blood gases, catalytic activity of
      phospholipase A2. RESULTS: In the fat embolism group, there were significant
      increases in mean pulmonary arterial pressure (p < 0.001), pulmonary vascular
      resistance (p < 0.001) and pulmonary shunting (p < 0.05) and simultaneously,
      systemic oxygenation was significantly impaired. The animals with fat embolism
      developed gradual fever and leucocytosis, whereas the catalytic activity of
      phospholipase A2 remained relatively unchanged. CONCLUSION: In this experimental
      model the measurement of serum phospholipase A2 activity does not provide a
      useful tool for the early detection of experimental fat embolism.

PMID- 9231858
TI  - Penile intracorporeal infusion--possible access to the systemic circulation.
      Pressure flow studies in dogs and humans.
AB  - OBJECTIVE: To assess penile intracorporeal infusion as a simple alternative
      method of intravenous access during the initial phase of fluid resuscitation in
      male patients. DESIGN: Laboratory pressure flow studies in dogs and in humans.
      SUBJECTS: 5 male mongrel dogs, and 10 male patients who were being investigated
      for psychogenic impotence (n = 5) or organic impotence (n = 5). INTERVENTIONS:
      Dogs- two 19G needles were inserted into the canine corpora cavernosa, one for
      fluid infusion, and the other for cavernosal pressure monitoring. Ringer's
      lactate solution was infused into the corpora cavernosa, through an infusion
      pump. The dogs were then bled until systolic blood pressure reached 60 mmHg, and
      resuscitated by transfusion of autologous blood into the corpora cavernosa.
      HUMANS: Ringer's lactate solution was infused into a corpus cavernosum through a
      19G scalp vein needle. Pressure monitoring was done through another 19 G needle.
      MAIN OUTCOME MEASURE: Fluid flow rates and in humans time taken to insert an
      intracorporeal needle. RESULTS: Mean (SD) infusion rate through the canine
      corpora was 110 (22) ml/minute for Ringer's lactate solution and 109 (18)
      ml/minute for autologous blood. Mean infusion rate into the human corpora was
      89.7 (12) ml/minute in the psychogenic impotent patients, and 88.2 (9) ml/minute
      in the organic impotent patients. Mean time taken to insert the needle was 15 (7)
      sec. CONCLUSIONS: An intracorporeal infusion line can be established in a short
      period of time and adequate quantities of fluids can be infused through the human
      and canine corpora cavernosa.

PMID- 9231860
TI  - Development of adenocarcinoma in Barrett's oesophagus after successful antireflux
      surgery.

PMID- 9231859
TI  - Effect of lactulose on bacterial translocation.
AB  - OBJECTIVE: To find out if lactulose can prevent the bacterial translocation that
      is induced by obstructive jaundice in rats. DESIGN: Laboratory experiment.
      SETTING: Teaching hospital, Turkey. MATERIAL: 50 male Wistar-albino rats.
      INTERVENTIONS: 10 rats were not operated on and used as controls; 20 rats
      underwent laparotomy and sham ligation of the common bile duct (CBD); 20 had the
      CBD ligated alone; and 20 had the CBD ligated and were given oral lactulose 2
      ml/day until death. All rats were killed after 14 days. MAIN OUTCOME MEASURES:
      Presence of Escherichia coli in mesenteric lymph nodes (MLN), and bacterial
      overgrowth as indicated by counts of E coli in the caecum. RESULTS: There was
      significantly less bacterial translocation to MLN in the group that had been
      given lactulose compared with CBD-ligated and lactulose not given (2/20 compared
      with 8/20, p = 0.06). There was also a significant reduction in the number of
      Gram negative bacteria in that group (p = < 0.01). CONCLUSION: Lactulose seems to
      reduce the incidence of translocation from the gut to MLN in rats with
      obstructive jaundice.

PMID- 9231861
TI  - Wernicke's encephalopathy after vertical banded gastroplasty for morbid obesity.

PMID- 9231862
TI  - Is 24-hour observation after laparoscopic cholecystectomy important for the
      identification of major vascular injury?

PMID- 9231863
TI  - Dyspareunia: more than bad sex.

PMID- 9231864
TI  - Differences among patients in opioid self-administration during bone marrow
      transplantation.
AB  - The distinctive features of individual patients, here termed individual
      differences, are inescapable aspects of day-to-day patient pain management, but
      classically designed research studies ignore such differences. This paper
      introduces statistical pattern visualization methodology for the study of complex
      individual differences in clinical settings. We demonstrate the application of
      such methods in patients undergoing bone marrow transplantation (BMT) and
      suffering severe oral mucositis as a consequence of the aggressive BMT
      preparative regimen. Oral mucositis produces severe pain and patients often
      require parenteral opioid medication for several weeks. Unfortunately, the opioid
      can cause side-effects that limit drug use for pain control. Patients differ in
      severity and duration of oral mucositis, analgesic response to opioids, and side
      effects. We identified and classified individual differences in patterns of drug
      use, pain control and side-effects in 33 BMT patients who received opioid drug
      via patient-controlled analgesia (PCA) systems for 7 days or more. These systems
      allowed bolus dosing and also provided a basic level of analgesic protection
      through continuous drug infusion. Continuous infusion levels increased or
      decreased in response to patient bolus self-administration. We employed
      statistical smoothing (moving average) techniques to remove random variation from
      the individual data sets and created three-way (trivariate) plots of change over
      time in drug use, pain and an opioid side-effect (impairment of concentration).
      The patterns apparent in these plots indicated that 24.2% of patients used PCA
      optimally (increases in drug use associated with reductions in pain and little or
      no side-effect), an additional 30.3% manifested a potentially optimal pattern
      limited by side-effect that worsened with dosing, and 36.4% used PCA suboptimally
      (modest pain control plus side-effects). In addition, for each subject we created
      a summary measure for the simultaneous change in three variables: the distance of
      each day's trivariate score from the origin of a three dimensional plot. This
      summary measure correlated significantly with the changing severity of patients'
      oral mucositis over time (r = 0.502). This study demonstrates how interactive
      graphic techniques can provide a basis for examining changes over time among
      multiple, correlated variables associated with a single individual. It
      illustrates the application of such techniques and demonstrates that individual
      subject data sets merit examination in cases where clinical data reflect human
      performance.

PMID- 9231865
TI  - Evidence for the involvement of spinal cord glia in subcutaneous formalin induced
      hyperalgesia in the rat.
AB  - Subcutaneous (s.c.) injection of formalin induces a rapid and prolonged
      hyperalgesia across widespread areas of the body. This hyperalgesic state
      involves a brain-to-spinal cord pathway, likely arising from the nucleus raphe
      magnus. The present study examined whether subsequent activation of spinal cord
      glia may be critical for the hyperalgesic state to be observed in rats. Glia were
      considered candidates as they can, upon activation, release a variety of
      substances known to be critical for the mediation of subcutaneous formalin
      induced hyperalgesia including glutamate, aspartate, nitric oxide, arachidonic
      acid and cyclooxygenase products such as prostaglandins. This series of
      experiments demonstrate that formalin-induced hyperalgesia in rats can be blocked
      by intrathecal administration of agents that: (a) disrupt glial function (using
      either 1 nmol fluorocitrate which is a glial metabolic inhibitor, or 9 microg CNI
      1493 which disrupts synthesis of nitric oxide and cytokines in monocyte-derived
      cells; ANOVA revealed reliable group effects for each drug with P < 0.0005); or
      (b) disrupt the action of glial products (using 10, 50, or 100 microg of a human
      recombinant interleukin-1 receptor antagonist or 10 microl antibody directed
      against nerve growth factor; ANOVA revealed reliable group effects for each drug
      with P < 0.001). Disruption appeared to be selective, as blockade of only select
      glial products was effective. That is, up to 120 microg of a functional
      antagonist of tumor necrosis factor-alpha (TNF binding protein) and 5 microl of
      an antibody against complement-3 produced no statistically reliable reduction in
      formalin-induced hyperalgesia. Taken together, the present series of experiments
      suggest an important role for spinal glial cells in the cascade of events that
      are initiated by descending signals following s.c. administration of formalin.

PMID- 9231866
TI  - Reversal of spinal cord non-opiate analgesia by conditioned anti-analgesia in the
      rat.
AB  - The spinal cord contains endogenous substances (such as cholecystokinin,
      FMRFamide, etc.) that can block the analgesic effects of opiates. Anti-opiate
      actions have been most commonly studied by exogenous administration of receptor
      agonists and receptor antagonists of these substances. However, we have recently
      demonstrated that anti-analgesia can be brought under environmental control
      through Pavlovian conditioning. Whereas analgesia can be conditioned to signals
      for danger, anti-analgesia can be conditioned to signals for safety. Using this
      paradigm, we have previously demonstrated that conditioned anti-analgesia can
      reverse a variety of opiate analgesic states, including those produced by
      conditioned danger signals, systemic morphine, and intrathecal mu- and delta
      opiate receptor agonists. These data raise the question of the generality of anti
      analgesia actions. The present series of experiments examined the ability of
      conditioned anti-analgesia to affect non-opiate analgesic states induced by
      spinal delivery of GABA(A), GABA(B), 5HT2 + 5HT1, and 5HT3 receptor agonists.
      While conditioned anti-analgesia had no effect on GABA(A) or 5HT2 + 5HT1 non
      opiate analgesias, conditioned anti-analgesia completely blocked GABA(B) and 5HT3
      non-opiate analgesias. These findings clearly demonstrate that conditioned anti
      analgesia can powerfully modulate non-opiate as well as opiate analgesias and
      bring into question whether putative anti-opiate neuroactive substances may have
      broader actions than previously suggested.

PMID- 9231867
TI  - The relationship between resting systolic blood pressure and cutaneous pain
      perception in cardiac patients with angina pectoris and controls.
AB  - In order to determine the influence of resting systolic blood pressure and stable
      angina on cutaneous pain perception, we studied 19 male cardiac patients with
      stable angina and 16 male controls. Pain perception was measured using a
      suprathreshold evaluation of pain intensity and pain unpleasantness to a series
      of thermal stimuli. We found that men with higher resting blood pressure had a
      decrease in the perception of pain intensity and pain unpleasantness. Similarly,
      we found that patients with stable angina perceived pain as less intense and
      unpleasant than controls. These differences in pain perception may be associated
      with different pain mechanisms: in the case of blood pressure, differences in
      opioid activity and baroreceptor-regulated pain systems; in the case of stable
      angina, patients may adapt to continued experiences of pain, altering internal
      frames of reference.

PMID- 9231868
TI  - The clinical significance of behavioral treatment for chronic low back pain: an
      evaluation of effectiveness.
AB  - The clinical effectiveness of behavioral treatment for chronic low back pain
      (CLBP) was evaluated using an empirical strategy to quantify individual patient
      change. Patients with CLBP (n = 17) presenting to an outpatient pain clinic were
      evaluated at baseline and six months posttreatment on variables of pain,
      disability and distress. Similar patients receiving usual medical care (n = 17)
      were evaluated on the same outcome measures and time line for purposes of
      descriptive comparison. Validated and widely-used measures of pain (McGill Pain
      Questionnaire), disability (Sickness Impact Profile), and depression (Beck
      Depression Inventory) served as outcome measures. Forty-seven percent of patients
      receiving behavioral treatment evidenced clinically significant improvement in at
      least one of the dimensions of pain, disability and depression associated with
      CLBP. However, clinically significant improvement across all three measures was
      rare. These findings are discussed in terms of the viability of behavioral
      treatment for CLBP, the need to enhance the degree of clinically significant
      outcome associated with behavioral treatments, and the value of empirical
      evaluation of clinically significant improvement following treatment
      interventions.

PMID- 9231869
TI  - A new automated method of pain scoring in the formalin test in rats.
AB  - The formalin test is a valuable tool widely used in animal pain studies. We offer
      a new automated technique based on continuous recording of movements of animals
      injected in a hindpaw with formalin (5%). This method, based on image processing,
      allows the discrimination of specific pain-induced behaviors and general motor
      activity. The comparison of the pain scores evaluated by manual and automated
      methods showed the same biphasic response. This new process was validated by
      using compounds known to alter pain responses to formalin: morphine and a non
      steroidal anti-inflammatory drug (ketoprofen). Morphine dose-dependently usually
      affects the two phases of formalin response with ED50 of 2.0 +/- 0.5 and 1.5 +/-
      0.5 mg/kg s.c. for the first and the second phase, respectively. The injection of
      ketoprofen significantly decreased pain scores of the second phase but not those
      of the first phase. The specificity of the method was studied by determining the
      effect of diazepam. This sedative compound induced a decrease in pain scores as
      well as a decrease in motor activity parameters. These data show that this
      automated technique can be considered as a relevant, sensitive and specific tool
      which allows the easier use of the formalin test especially for the screening of
      analgesic drugs.

PMID- 9231870
TI  - Inhibition of substance P release from spinal cord tissue after pretreatment with
      capsaicin does not mediate the antinociceptive effect of capsaicin in adult mice.
AB  - Substance P (SP) is released from primary afferent fibers in response to
      nociceptive stimuli. Capsaicin, which produces an initial hyperalgesic response
      followed by persistent antinociception, also elicits release of SP from primary
      afferent fibers. Capsaicin pretreatment decreases the content and release of SP
      from primary afferent fibers. This effect on SP has been hypothesized to mediate
      the antinociceptive effect of capsaicin. To test this hypothesis, mice were
      injected intrathecally (i.t.) with antinociceptive doses of capsaicin or SP(1-7)
      before superfusion of spinal cord tissue with 3 microM capsaicin 24, 48, 96 or
      168 h later. N-terminal metabolic fragments of SP that accumulate after capsaicin
      induced SP release and are involved in the antinociceptive effect of capsaicin,
      were also tested. Like capsaicin SP(1-3), SP(1-4) and SP(1-7) were each
      antinociceptive when injected 24 h before nociceptive testing. However, at this
      time there was no decrease in capsaicin-evoked release of SP in tissue from
      capsaicin- and SP(1-7)-pretreated animals compared to those injected with
      vehicle. In contrast, capsaicin-evoked SP release decreased significantly in
      tissue from mice pretreated with capsaicin or SP(1-7) 48 h prior to testing. D
      Substance P(1-7), which prevents antinociception, blocked capsaicin- and SP(1-7)
      induced decreases in SP release, indicating that these effects are mediated by SP
      N-terminal activity. Total spinal cord content of SP did not differ amongst
      treatment groups. These data indicate that antinociception does not appear to
      depend on decreases in SP release or content as antinociception precedes
      decreases in SP release.

PMID- 9231871
TI  - Enhancing sensitivity to facial expression of pain.
AB  - Clinicians have long appreciated the information communicated by a patient's
      facial expression. Advances in the measurement of facial movements, using the
      Facial Action Coding System (FACS) have allowed for identification of a universal
      expression of pain, which is primarily encoded in four facial movements. While
      the FACS provides a rigorous assessment of facial expression, the time required
      to learn the system and to analyze the facial expression by use of slow motion
      video recording, makes its use impractical in the clinical setting. The purpose
      of this research was to examine whether exposure to a brief training procedure,
      based on orienting subjects to the four facial movements, would increase
      sensitivity to pain communicated by facial expression. Seventy-five occupational
      and physical therapy student volunteers were randomly assigned to training or
      control groups. The trained group was exposed to a 30-min training session. Both
      groups were then asked to rate a videotape of patients undergoing assessment of a
      painful shoulder and rate the amount of discomfort the patients appeared to be
      experiencing. Analyses indicated that the trained group was significantly more
      sensitive to subtle facial movements associated with low levels of pain. Relative
      to the patients' ratings, there was a tendency for raters to underestimate pain
      particularly when these were at a high level. The findings lend hope to the
      feasibility of developing a tool which would be clinically useful though this may
      be more difficult for observers judging more complex facial expressions
      associated with high levels of pain.

PMID- 9231872
TI  - Distinct electrophysiological effects of two spinally administered membrane
      stabilising drugs, bupivacaine and lamotrigine.
AB  - A selective blockade of the relay of messages by C-fibres into the spinal cord is
      a logical approach to the reduction of nociceptive transmission. Here we compared
      the effect of two distinctly different sodium channel blockers, the local
      anaesthetic bupivacaine and the novel anti-epileptic lamotrigine, on the
      responses of dorsal horn neurones following noxious and innocuous stimulation.
      Dorsal horn neuronal responses following acute repetitive C-fibre electrical
      stimulation (three times the C-fibre threshold at 0.5 Hz) were recorded in intact
      halothane anaesthetised rats. Wind up, an enhanced C-fibre evoked response of
      dorsal horn neurones, and an associated post discharge were observed following
      repetitive stimulation. The effects of spinally administered bupivacaine and
      lamotrigine on the dorsal horn neuronal responses were investigated. Spinal
      bupivacaine (25-1000 microg/50 microl) dose dependently reduced the C-fibre
      evoked responses (r2 = 0.5, P < 0.0003), wind up (r2 = 0.4, P < 0.002) and the
      post discharge (r2 = 0.34, P < 0.005) of these neurones. The effects of
      bupivacaine were long lasting, up to 120 min post-administration. The Abeta-fibre
      evoked responses were not dose-dependently reduced by bupivacaine. Spinal
      lamotrigine (50-1000 microg/50 microl) did not significantly reduce the C- or
      Abeta-fibre evoked responses. In contrast there was a tendency for wind up and
      post discharge to be facilitated by lamotrigine. Although both bupivacaine and
      lamotrigine are sodium channel blockers, the effects of the two drugs on the C
      fibre and Abeta-fibre evoked responses were completely different. Bupivacaine
      reduced C-fibre evoked responses whereas lamotrigine had a tendency to facilitate
      responses. The profile of sodium channel blockers would appear highly diverse and
      the status of lamotrigine as a potential analgesic remains unclear.

PMID- 9231873
TI  - Accuracy of children's pain memories.
AB  - Despite its importance in clinical practice, little research has examined memory
      for pain in children. This prospective study tried to justify the use of
      children's pain recall in clinical practice. The purpose of this study was to (a)
      investigate the accuracy of children's recall of their worst and average pain
      intensity when controlling for the effects of repeated pain measurement and (b)
      examine the influence of children's anxiety, age, general memory ability and pain
      coping strategies on this accuracy. The accuracy of children's recalled pain
      intensities was studied in 55 inpatients aged 5-16 years by comparing the level
      of recorded pain intensity with the level of recalled pain intensity 1 day and 1
      week after recording using Bieri's Faces Pain Scale. The accuracy of children's
      recalled pain intensities was high and showed little decrement over 1 week. Older
      children had more accurate recall of their worst pain intensity. Anxiety, general
      memory ability and pain coping strategies were not related to accuracy of
      recalled pain intensities.

PMID- 9231874
TI  - Prostaglandin E receptor EP3 subtype is involved in thermal hyperalgesia through
      its actions in the preoptic hypothalamus and the diagonal band of Broca in rats.
AB  - The effects of microinjection of prostaglandin E2 (PGE2) (0.5 fg-500 pg/0.2
      microl) into the medial part of the preoptic area (MPO) on nociception were
      studied using a hot-plate test in rats. The intraMPO microinjection of PGE2 only
      at non-pyrogenic doses (5-50 fg) reduced the paw-withdrawal latency, suggesting
      hyperalgesia. Maximal reduction was obtained 15 min after the injection of PGE2
      at 50 fg. Subsequently, to determine which types of prostanoid receptors are
      involved in the hyperalgesic effect of PGE2 in the MPO, we administered PGE2
      receptor agonists, i.e., 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist),
      butaprost (an EP2 receptor agonist) and M&B28767 (an EP3 receptor agonist) into
      the MPO and observed the nociceptive behavior. The intraMPO injection of M&B28767
      (0.005 fg-50 pg), like that of PGE2, exhibited a U-shaped dose response
      characteristic, i.e., a significant decrease of the paw-withdrawal latency only
      at 0.05-5 fg with the maximal response at 0.5 fg. However, neither the
      administration of EP1 (0.5 fg-50 ng) nor EP2 (0.5 fg-500 pg) agonists had any
      effect on nociception. The microinjection of M&B28767 at 0.5 fg into the other
      parts of preoptic hypothalamus (the lateral part of the preoptic area and the
      median preoptic nucleus) and the diagonal band of Broca (DBB) produced
      hyperalgesia similar to the intraMPO-induced hyperalgesia in terms of magnitude
      and time course. Microinjection of M&B28767 (0.5 fg) into either the
      paraventricular nucleus, the ventromedial hypothalamus, the lateral hypothalamic
      area or the septal nucleus had no effect on nociception. These findings suggest
      that PGE2 at non-pyrogenic doses in the brain induces hyperalgesia, at least in
      part, through its actions on EP3 receptors in the preoptic hypothalamus and the
      DBB in rats.

PMID- 9231875
TI  - Antinociception induced by civamide, an orally active capsaicin analogue.
AB  - The antinociceptive effects of a novel capsaicin analogue, civamide (cis-8-methyl
      N-vanillyl-6-nonenamide), given orally to adult rats were examined. In the
      formalin test, civamide significantly suppressed the flinch response,
      particularly phase 2, in a dose-dependent fashion (20-200 mg/kg). This inhibitory
      effect started 1 h after application, and was maintained for 4-7 days. A
      competitive capsaicin antagonist, capsazepine (15 mg/kg, s.c.), reversed the
      antinociceptive action of civamide (200 mg/kg) on the formalin test when it was
      given either 5 min or 55 min after oral civamide delivery. In contrast,
      capsazepine delivered 2 days after civamide had no effect upon the depressed
      formalin response. Civamide produced a significant increase in the response
      latency on the thermal paw withdrawal test, which persisted for 2-3 days.
      Civamide produced a modest, but statistically significant, reversal of low
      tactile thresholds otherwise observed in the Chung neuropathic rats. Morbidity
      (approximately 10%) was observed which was secondary to bronchial constriction
      occurring with gastric reflux. Civamide at the doses given did not produce motor
      dysfunction. Neither calcitonin gene-related peptide (CGRP) nor substance P (SP)
      concentrations in dorsal or ventral spinal cord were altered by civamide (200
      mg/kg) up to 5 days, whereas CGRP, but not SP, in dorsal root ganglia (DRG) and
      sciatic nerves was modestly reduced at 1 day after the delivery. These data
      suggest that an orally bioavailable capsaicin analogue, civamide, possessed
      analgesic activity with respect to several noxious stimuli, including
      inflammation-induced hyperalgesia, noxious thermal stimulation and nerve injury
      induced tactile allodynia. The rapid onset and lack of change in the peptide
      levels in dorsal spinal cord suggests that the analgesic action of civamide is
      primarily a result of desensitization at the afferent terminals. The
      antinociception of civamide is probably mediated by at least two mechanisms: (i)
      an acute receptor occupancy dependent effect; and (ii) a persistent and receptor
      independent effect which is initiated by the acute exposure to the drug.

PMID- 9231876
TI  - Psychological dysfunction in patients with reflex sympathetic dystrophy.
AB  - Patients with reflex sympathetic dystrophy (RSD) often present with pain and
      disability that cannot be explained on the basis of objective physical findings.
      This has led some to speculate that RSD may be caused or mediated by non-organic
      factors. Unfortunately, there have been few studies using standardized measures
      of mood and illness behavior that have compared patients with RSD to patients
      with other chronic pain disorders. The goal of the present study, therefore, was
      to compare the pattern of psychological dysfunction in patients with RSD to the
      pattern of dysfunction in patients with chronic back pain and local neuropathic
      pain. Patients with back pain resemble those with RSD in that both may report
      symptoms that cannot be reconciled with objective physical findings. Patients
      with local neuropathy, by contrast, report pain that is both circumscribed and
      consistent with a known organic cause. The records of 253 patients attending a
      tertiary pain service were retrospectively reviewed and three distinct (non
      overlapping) diagnostic groups were formed: 25 were assigned to the RSD group; 44
      to the back pain group; and 21 to the local neuropathy group. Using a set of
      stringent criteria to diagnose RSD and an analysis of covariance to control for
      differences in symptom duration and age, the present study found no evidence to
      suggest that patients with RSD were psychologically unique. Instead, RSD patients
      were remarkably similar to those with local neuropathy in terms of their symptom
      reporting, illness behavior, and psychological distress. The only exception was
      that RSD patients had more disability days during the preceding 6 months than
      those with local neuropathy (P < 0.05). The back pain group, on the other hand,
      presented with more diffuse pain complaints (P < 0.05) and had a greater number
      of non-specific medical symptoms (P < 0.05) compared to either the RSD or local
      neuropathy group. In contrast to previous research using less stringent
      diagnostic criteria, there was no evidence of higher pain scores or lower levels
      of psychological distress among patients with RSD. In addition, a validated
      survey of childhood trauma found that sexual abuse, physical abuse, emotional
      abuse, and cumulative trauma were evenly distributed among all three diagnostic
      groups. The burden of proof would appear to be upon those who advocate the non
      organic hypothesis to provide credible evidence of psychological involvement in
      the etiology of RSD.

PMID- 9231877
TI  - A pain in the head.

PMID- 9231878
TI  - Computational gene identification.

PMID- 9231879
TI  - Familial glucocorticoid deficiency: one syndrome, but more than one gene.
AB  - Familial glucocorticoid deficiency is a rare autosomal recessive disease
      characterised by resistance to the action of ACTH. A number of mutations in the
      ACTH receptor have been demonstrated in patients with this disorder which are
      likely to lead to loss of receptor function and thus would account for the
      syndrome. Several patients, however, do not have mutations in the ACTH receptor
      gene coding region, and it can be demonstrated by segregation analysis that
      another distant gene must account for the disease in some of these cases. The
      nature of several candidate genes for this normal receptor form of the disease is
      discussed.

PMID- 9231880
TI  - Cellular and molecular analyses of major histocompatibility complex (MHC)
      restricted and non-MHC-restricted effector cells recognizing renal cell
      carcinomas: problems and perspectives for immunotherapy.
AB  - Renal cell carcinomas belong to the small group of tumors that are able to induce
      antitumor responses. Here we describe two general types of cytotoxic effector
      lymphocytes that can eliminate autologous tumor cells and discuss the role that
      major histocompatibility complex encoded molecules play in governing their
      specificities. Improved understanding of the cellular and molecular basis of
      renal cell carcinoma recognition opens new avenues of research with the potential
      to develop better immunotherapies for patients with metastatic disease.

PMID- 9231881
TI  - Testing for interference in human genetic maps.
AB  - Known methods of testing for interference in human genetic maps are reviewed. Two
      aspects of interference are distinguished, numerical interference referring to
      the numbers of crossovers occurring and positional interference referring to the
      positions of crossovers. Tests for interference generally address only one or the
      other of these two aspects. Published investigations of interference presume
      fully informative marker maps, while in reality genetic markers are of limited
      heterozygosity, which weakens some of the tests for interference. The conclusion
      is drawn that rigorous tests for interference have not yet been carried out for
      human data.

PMID- 9231882
TI  - The canalicular multispecific organic anion transporter and conjugated
      hyperbilirubinemia in rat and man.
AB  - The human Dubin-Johnson syndrome is an autosomal recessive liver disease
      characterized by a chronic conjugated hyperbilirubinemia. Patients have impaired
      hepatobiliary transport of many endogenous and xenobiotic compounds. A similar
      disease phenotype has been described for a naturally occurring mutant Wistar rat
      strain, the TR- rat, which is defective in the, functionally defined, canalicular
      multispecific organic anion transporter (cMOAT). The complementary DNA encoding
      this protein has been cloned from rat and recently from human liver. cMOAT is a
      new member of the ATP-binding cassette transporter family, and homologous to the
      multidrug resistance-associated protein 1. A mutation in the cMOAT gene is
      responsible for the phenotype observed in TR- rats. This information should soon
      lead tc a complete genetic characterization of the human Dubin-Johnson syndrome.

PMID- 9231883
TI  - Multistep carcinogenesis of breast cancer and tumour heterogeneity.
AB  - Breast cancer emerges by a multistep process which can be broadly equated to
      transformation of normal cells via the steps of hyperplasia, premalignant change
      and in situ carcinoma. The elucidation of molecular interdependencies, which lead
      to development of primary breast cancer, its progression, and its formation of
      metastases is the main focus for new strategies targetted at prevention and
      treatment. Cytogenetic and molecular genetic analysis of breast cancer samples
      demonstrates that tumour development involves the accumulation of various genetic
      alterations including amplification of oncogenes and mutation or loss of tumour
      suppressor genes. Amplification of certain oncogenes with concomitant
      overexpression of the oncoprotein seems to be specific for certain histological
      types. Loss of normal tumour suppressor protein function can occur through
      sequential gene mutation events (somatic alteration) or through a single
      mutational event of a remaining normal copy, when a germline mutation is present.
      The second event is usually chromosome loss, mitotic recombination, or partial
      chromosome deletion. Chromosome loci 16q and 17p harbour tumour suppressor genes,
      which seem to be pathognomonic for the development or progression of a specific
      histological subtype. There are an overwhelming number of abnormalities that have
      been identified at the molecular level which fit the model of multistep
      carcinogenesis of breast cancer. When the functions of all of these genes are
      known and how they participate in malignant progression, we will have the tools
      for a more rational approach to diagnosis, prevention and treatment. This review
      deals only with the factors that are involved in the conversion of a normal
      breast cell into a malignant cell rather than those required for invasion and
      metastases. A key critical long-term step in the molecular analysis of breast
      cancer will be to link the specific molecular damage with the effects of
      environmental carcinogens.

PMID- 9231884
TI  - Molecular regulation of human IgE synthesis.
AB  - Understanding the induction and regulation of IgE synthesis in human B cells is
      crucial to elucidate the molecular pathogenesis of IgE-dependent diseases.
      Experimental data, in part supported by clinical observations, suggests that IgE
      regulation is a complex process involving several cellular and molecular
      interactions. A two-signal model is accepted for the induction of IgE synthesis
      in human B cells. The first signal is provided by the cytokines interleukin 4 or
      13, which are secreted by T cells, mast cells, and basophils. The second signal
      for the induction of IgE synthesis requires cell contact between T and B cells.
      Engagement of the B cell antigen CD40 by the CD40 ligand (CD40L) expressed on T
      cells leads to subsequent isotype switching during immunoglobulin synthesis in B
      cells. The CD40-CD40L interaction is well established as a key signal for the
      induction of isotype switching while the elucidation of the role of other cell
      cell interactions, for example, through adhesion molecules, needs further study.
      An important counteracting cytokine for IgE synthesis is interferon (IFN) gamma
      which is produced mainly by T lymphocytes. Several cell-contact molecules,
      cytokines, and various hormones have been shown to modulate IgE synthesis in
      vitro, suggesting a complex network of molecular events to be involved in the
      production of IgE. However, the relevance of these factors for IgE production in
      vivo requires further elucidation. Here we describe the molecular mechanisms
      known to be involved in the induction and regulation of human IgE synthesis and
      discuss the role of various molecules during this process. Furthermore, evidence
      is presented that the understanding of IgE synthesis provides a potential key for
      new therapeutic strategies in patients with IgE mediated diseases including
      atopic dermatitis.

PMID- 9231885
TI  - Inhibition of intercellular adhesion molecule-1 (ICAM-1), soluble ICAM-1 and
      interleukin-4 by nitric oxide expression in migraine patients.
AB  - The mechanisms of the postulated "sterile" inflammation in migraine were studied
      utilizing flow cytometry (intercellular adhesion molecule 1, ICAM-1; interleukin
      1 receptor, IL-1R) and enzyme-linked immunosorbent assay (soluble intercellular
      adhesion molecule 1, sICAM-1; interleukin-4, IL-4). Twenty patients suffering
      from migraine without aura, 20 healthy subjects, and 10 patients suffering from
      episodic tension headache were selected. All of the migraine patients were
      studied during a migraine crisis experimentally induced by the administration of
      isosorbide dinitrate (a nitric oxide donor), and 10 out the 20 were also studied
      during a spontaneous migraine attack. A sharp decrease in the expression of ICAM
      1 (F=5.09, p<0.001 and F=2.46, p<0.05, respectively), sICAM-1 1 (F=6.21, p<0.0001
      and F=3.99, p<0.007, respectively) and serum IL-4 (F=6.23, p<0.001 and F=3.64,
      p<0.01, respectively) were observed in experimentally induced and spontaneous
      migraine attacks. There was no change with respect to IL-IR 1 receptor expression
      values. The two control groups, tested with the same experimental procedure,
      showed no changes in ICAM-1 and IL-1R or in in sICAM-1 and IL-4. Our data suggest
      that migraine patients are more sensitive to exogenous NO than controls. In
      addition, our results indicate that experimental migraine crisis, induced by an
      NO donor, is mediated by the inhibition of IL-4 and subsequently of ICAM-1. It is
      likely that the described ICAM-1 downregulation inhibits during a migraine attack
      the critical step of transendothelial migration into the cerebral tissues of
      activated leukocytes, as proposed in the "sterile inflammation" hypothesis.

PMID- 9231886
TI  - Linkage between postabsorptive amino acid release and glutamate uptake in
      skeletal muscle tissue of healthy young subjects, cancer patients, and the
      elderly.
AB  - Several diseases of varying etiology that are commonly associated with the loss
      of skeletal muscle mass were found to be associated with a decrease in muscular
      glutamate and glutathione levels and in glutamate uptake in the postabsorptive
      state. In view of the Na+ dependency and insulin responsiveness of glutamate
      transport we studied the postabsorptive glutamate exchange in more detail. Our
      study demonstrates a linkage between glutamate uptake and the export of other
      amino acids, suggesting that protein catabolism and the resulting coexport of
      amino acids plus Na+ substitute for insulin as a driving force for the Na+
      gradient in the postabsorptive state. The regression function of the correlation
      between relative glutamate exchange and cumulative amino acid exchange in cancer
      patients was lower than that in non-tumor-bearing subjects, suggesting that
      cancer patients must release more amino acids to achieve the same glutamate
      uptake. In addition, cancer patients had a lower average cumulative amino acid
      exchange rate than non-tumor-bearing subjects, suggesting that the abnormally low
      relative glutamate exchange capacity of cancer patients results mainly from
      inadequate postabsorptive protein catabolism in the skeletal muscle tissue. Both
      cancer patients and non-tumor-bearing elderly subjects had higher arterial
      glutamate levels and alanine release than young subjects, indicative of a
      substantial glycolytic activity in the skeletal muscle. However, elderly non
      tumor-bearing subjects showed, in contrast to cancer patients, in the
      postabsorptive state a stronger cumulative amino acid release and postabsorptive
      glutamate uptake than healthy young subjects. These changes are discussed in view
      of the age-related loss of skeletal muscle mass.

PMID- 9231887
TI  - Combination therapy: a key to comprehensive patient care.

PMID- 9231888
TI  - Blood pressure control for the hypertensive patient: what can we do better?

PMID- 9231889
TI  - Combination antihypertensive therapy: does it have a role in rational therapy?
AB  - The pharmacological treatment of hypertension allows one to reduce substantially
      the risk of developing a cardiovascular complication. It appears more and more
      important to bring blood pressure to normal values in order to get the maximal
      benefit from antihypertensive therapy. Blood pressure lowering drugs make it
      possible to control blood pressure in about half of the patients when
      administered as monotherapy. The fraction of patients with a normal blood
      pressure can be markedly increased by combining drugs acting by different
      mechanisms. Low doses of antihypertensive agents are generally enough when
      coadministered. This helps to keep the incidence of side effects minimal and
      facilitates the patient's compliance with long-term treatment. Low-dose, fixed
      dose combination therapy may therefore represent a valuable option not only to
      treat hypertensive patients unresponsive to drugs given as monotherapy, but also
      to initiate the treatment.

PMID- 9231890
TI  - Fixed-dose combination therapy with trandolapril and verapamil SR is effective in
      primary hypertension. Trandolapril Study Group.
AB  - We assessed the efficacy of monotherapy with trandolapril, an angiotensin
      converting enzyme (ACE) inhibitor, and of verapamil slow-release (SR), a calcium
      antagonist, each in a range of three doses as monotherapy, and in the nine
      possible combinations of therapy in patients with stage I to III diastolic
      hypertension. After 4 weeks of single-blind placebo, 746 patients in 39 study
      centers were randomized to one of the 16 double-blind treatments for 6 weeks
      (placebo; verapamil SR monotherapy 120, 180, or 240 mg; trandolapril monotherapy
      0.5, 2, or 8 mg; and trandolapril/verapamil SR combinations 0.5/120, 0.5/180,
      0.5/240, 2/120, 2/180, 2/240, 8/120, 8/180, or 8/240 mg. Both mono- and
      combination therapies achieved the primary efficacy parameters: lowered supine
      diastolic blood pressure (at trough) more than placebo, P < .01 (except 0.5 mg
      trandolapril, 0.5/180 and 2/120 combinations, P < .05, and the 120 mg verapamil
      SR, P = NS). The therapies yielded a trough to peak ratio of >0.52 and had higher
      percentages of responders as compared with placebo (P < .01, < .05). Supine
      systolic blood pressures were lowered more by combination therapy than the
      respective monotherapies, P < .05, P < .01, except the 8/120 combination.
      Combination therapy was more effective than monotherapy for sitting diastolic
      blood pressure, P < .05. The percentage of patients with adverse reactions were
      similar for mono- and combination therapy. Trandolapril had a greater "apparent"
      incremental effect on the systolic blood pressure reductions than verapamil SR.

PMID- 9231891
TI  - Cardiac effects of combination therapy.
AB  - Control of hypertension and treatment of concomitant pathophysiologic conditions
      require use of multiple drugs. Unfortunately, most studies regarding hypertensive
      disease have focused on monotherapy. Thus, our knowledge of combination therapy
      in the treatment of hypertension is, to a great extent, extrapolation from
      monotherapy. Angiotensin converting enzyme (ACE) inhibitors in combination with
      calcium antagonists should be particularly efficacious in reducing left
      ventricular hypertrophy (LVH). Drug classes that either stimulate the renin
      angiotensin system or the sympathetic nervous system are less likely to reduce
      LVH and should be avoided. In hypertensive patients with congestive heart
      failure, amlodipine should be added to triple therapy with an ACE inhibitor,
      whereas in the postmyocardial ischemia patient, verapamil may exert some
      additional beneficial effects with regard to reinfarction rates. Given that two
      drugs when used separately are beneficial in a disorder does not necessarily mean
      that their combination is equally or even more beneficial. Thus, combination
      therapy should primarily be used for lowering arterial pressure and only
      secondarily to possibly improve concomitant pathophysiologic conditions
      associated with hypertensive heart disease.

PMID- 9231892
TI  - Combination treatment in hypertension: the VeraTran Study.
AB  - In the past few years, the combination of two antihypertensive drugs has become a
      popular approach to hypertension treatment, because this procedure allows one to
      obtain satisfactory blood pressure control when monotherapy is partially
      ineffective and also to improve a patient's adherence to the therapeutic regimen,
      thereby enhancing the tolerance/effectiveness ratio of the treatment. This paper
      will briefly review the theoretical background and the requirements for an
      effective combination treatment. It will also discuss the results of the VeraTran
      Study, a multicenter study performed according to a double-blind parallel group
      design and aimed at assessing the antihypertensive efficacy of the fixed
      combination verapamil slow release (SR) and trandolapril, administered for 8
      weeks, on clinic and 24-h ambulatory blood pressure. The results of the study
      demonstrate that the fixed combination of a calcium antagonist and an angiotensin
      converting enzyme (ACE) inhibitor allows one to obtain an effective and balanced
      blood pressure control throughout the 24 h.

PMID- 9231893
TI  - Protecting the residual renal function: which drugs of choice?
AB  - Diabetic nephropathy is a major cause of illness and premature death in diabetic
      patients, largely through accompanying cardiovascular disease and end-stage renal
      failure. Proteinuria heralds the clinical nephropathy, and the worsening of
      proteinuria parallels the progression of renal disease towards chronic renal
      failure. A large body of evidence has accumulated that emphasizes the role of
      elevated blood pressure in the progression of renal disease, as well as the clear
      benefit of antihypertensive treatment. However, the choice of antihypertensive
      drug to protect renal function was less clear in the past. In earlier studies, a
      reduction in the rate of progressive renal failure in hypertensive subjects has
      been shown with diuretics, beta-blockers, and vasodilators. However, there is now
      increasing evidence that angiotensin converting enzyme (ACE) inhibitors and some
      calcium antagonists produce a more beneficial effect on nephropathy in terms of
      reducing proteinuria and slowing progression to renal failure. These drugs are
      attributed nephroprotective capacity beyond their systemic blood pressure
      lowering effects, and initial clinical trials with combinations have revealed
      additive nephroprotective effects. Finally, ACE-inhibitors and calcium
      antagonists have no adverse effects on glycemic control or lipid levels and may
      even improve insulin sensitivity. This further promotes these antihypertensives
      to first-line drugs when treating subjects at risk of metabolic disorders or
      people with diabetes.

PMID- 9231894
TI  - The challenge of managing multiple cardiovascular risk factors.
AB  - Hypertensive patients have an excess of other cardiovascular risk factors.
      Moreover, traditional therapy based on diuretics and beta-blockers may aggravate
      these risk factors. Therefore, attention must be given to the identification of
      all pertinent risk factors and their amelioration by appropriate therapy. Such
      therapy must include lifestyle changes including cessation of smoking, reduction
      of obesity, moderation of sodium intake and alcohol consumption, and increased
      physical activity. When antihypertensive drugs are chosen, consideration should
      be given to their potential influences, either negative or positive, on other
      cardiovascular risk factors. In particular, the adverse effects of diuretics and
      beta-blockers on lipids and insulin sensitivity may preclude their use. alpha
      Blockers and ACE inhibitors may have beneficial effects on these metabolic
      indices. Calcium antagonists are neutral in most regards. Whatever agents are
      chosen, the use of low doses in combination is being increasingly recognized as a
      better way to achieve the desired antihypertensive efficacy while minimizing
      adverse effects. As has been noted in the other papers in this supplement, the
      combination of an ACE inhibitor and a calcium antagonist is particularly
      attractive, not only to treat hypertension, but also to ameliorate other
      cardiovascular risk factors.

PMID- 9231895
TI  - Ta6Br(2+)12, a tool for phase determination of large biological assemblies by X
      ray crystallography.
AB  - The title compound Ta6Br(2+)12 is of interest for the analysis of biological
      structures as a heavy-metal derivative with great potential for the structure
      determination of large protein systems. In macromolecular crystallography the
      phases of the measured structure factor amplitudes have to be determined. The
      most widely used method for novel structures is isomorphous replacement by
      introducing electron-rich compounds into the protein crystals. These compounds
      produce measurable changes of the diffraction intensities, which allow phase
      determination. We synthetized the Ta6Br(2+)12 cluster in high yields,
      crystallized it, and determined its crystal structure by X-ray diffraction
      analysis at atomic resolution. The cluster is a regular octahedron consisting of
      six metal atoms with 12 bridging bromine atoms along the 12 edges of the
      octahedron. The cluster is compact, of approximately spherical shape with about
      4.3 A radius and highly symmetrical. One Ta6Br(2+)12 ion adds 856 electrons to a
      protein, a considerable contribution to the scattering power even of large
      proteins or multimeric systems. At low resolution all atoms of the cluster
      scatter in phase and act as a super heavy-atom, which is easy to locate in the
      difference Patterson map. We investigated its binding sites in the biologically
      significant high-resolution structures of an antibody V(L) domain, dimethyl
      sulfoxide reductase, GTP-cyclohydrolase I, and the proteasome. With the randomly
      oriented cluster, treated as a single site scatterer, phases could be used only
      up to 6 A resolution. In contrast, when the cluster is correctly oriented, phases
      calculated from its 18 atom sites can be used to high resolution. We present the
      atomic structure of the Ta6Br(2+)12, describe a method to determine its
      localization and orientation in the unit cell of protein crystals of two
      different proteins, and analyse its phasing power. We show that phases can be
      calculated to high resolution. The phase error is lower by more than 30 degrees
      compared to the single site approximation, using a resolution of 2.2 A.
      Furthermore, Ta6Br(2+)12 has two different strong anomalous scatterers tantalum
      and bromine to be used for phase determination.

PMID- 9231896
TI  - NMR analysis of the interaction between protein L and Ig light chains.
AB  - Protein L is a cell wall protein expressed by some strains of the anaerobic
      bacterial species Peptostreptococcus magnus. It binds to immunoglobulin (Ig)
      light chains predominantly of the kappa subtype from a wide range of animal
      species. This binding is mediated by five highly homologous repeats designated as
      B1-B5, each of which comprises 72 to 76 amino acid residues. The fold of the Ig
      light chain-binding B1 domain of protein L has previously been shown to comprise
      an alpha-helix packed against a four-stranded beta-sheet. The Ig-binding region
      of the protein L domain involves most of the residues in the second beta-strand,
      the C-terminal residues of the alpha-helix, and residues in the loop connecting
      the alpha-helix with the third beta-strand. In the present study, we have
      identified the protein L-binding site of an Ig light chain by use of stable
      isotope-assisted NMR spectroscopy. The light chain of a murine monoclonal anti
      17alpha-hydroxy-progesterone Fab fragment (IgG2b, kappa) was selectively labeled
      with 13C at carbonyl groups of Ala, Arg, Cys, Ile, Lys, Met, Phe, Trp, or Tyr.
      The residues in which the carbonyl 13C chemical shift was significantly perturbed
      upon binding of the protein L B1 domain were preferentially found in the second
      beta-strand of the variable kappa domain and parts of its flanking beta-strands.
      None of these residues were affected by the addition of the antigen against which
      the monoclonal Fab fragment is directed. Therefore, we conclude that protein L
      binds to the outer surface of the framework region of the V(L) domain, primarily
      involving the V(L) second strand, and that this binding is independent of antigen
      binding. The present NMR data, in combination with sequence comparisons between
      kappa light chains with and without protein L affinity, suggest that the amino
      acid substitutions at positions 9, 20, and/or 74 of the kappa light chains could
      crucially affect the interaction between protein L and the V(L) domain.

PMID- 9231897
TI  - Regulation of the "tetCD" genes of transposon Tn10.
AB  - In addition to the genes involved in tetracycline resistance, the loop region of
      the composite transposon Tn10 contains two other known genes, tetC and tetD,
      whose functions are unclear. Using primarily a genetic approach, we examined
      tetCD gene expression and regulation. The tetC gene product, TetC, is a
      diffusible repressor of both tetC and tetD transcription. Despite an earlier
      claim by others, we do not detect induction of either tetC or tetD by
      tetracycline (Tc) or several of its analogs. Although the 5' ends of the tetC and
      tetD messages overlap due to transcription from convergent promoters, we find no
      evidence for anti-sense RNA control. The operator for the TetC repressor has been
      localized. We also demonstrate that transcription from the tetD promoter probably
      terminates within IS10-Right and does not apparently interfere with Tn10 or IS10
      Right transposition or its regulation.

PMID- 9231898
TI  - Stable heterodimers from remodeling the domain interface of a homodimer using a
      phage display library.
AB  - Structure-guided phage display was used to select for combinations of interface
      residues for antibody C(H)3 domains that promote the formation of stable
      heterodimers. A C(H)3 "knob" mutant was made by replacement of a small residue,
      threonine, with a larger one, tryptophan: T366W. A library of C(H)3 "hole"
      mutants was then created by randomizing residues 366, 368 and 407, which are in
      proximity to the knob on the partner C(H)3 domain. The C(H)3 knob mutant was
      fused to a peptide flag and the C(H)3 hole library was fused to M13 gene III.
      Phage displaying stable C(H)3 heterodimers were recovered by panning using an
      anti-flag antibody. Phage-selected C(H)3 heterodimers differed in sequence from
      the previously designed heterodimer T366W-Y407'A, and most clones tested were
      more stable to guanidine hydrochloride denaturation. The thermal stability of
      individual C(H)3 domains secreted from Escherichia coli was analyzed by
      differential scanning calorimetry. One heterodimer, T366W-T366'S:L368'A:Y407'V,
      had a t(m) of 69.4 degrees C, which is 4.0 deg.C higher than that for the
      designed heterodimer and 11.0 deg.C lower than that for the wild-type homodimer.
      The phage-selected C(H)3 mutant maintained the preference for forming
      heterodimers over homodimers as judged by near-quantitative formation of an
      antibody/immunoadhesin hybrid in a cotransfection assay. Phage optimization
      provides a complementary and more comprehensive strategy to rational design for
      engineering homodimers for heterodimerization.

PMID- 9231899
TI  - Non-canonical interactions in a kissing loop complex: the dimerization initiation
      site of HIV-1 genomic RNA.
AB  - Retroviruses encapsidate two molecules of genomic RNA that are noncovalently
      linked close to their 5' ends in a region called the dimer linkage structure
      (DLS). The dimerization initiation site (DIS) of human immunodeficiency virus
      type 1 (HIV-1) constitutes the essential part of the DLS in vitro and is crucial
      for efficient HIV-1 replication in cell culture. We previously identified the DIS
      as a hairpin structure, located upstream of the major splice donor site, that
      contains in the loop a six-nucleotide self-complementary sequence preceded and
      followed by two and one purines, respectively. Two RNA monomers form a kissing
      loop complex via intermolecular interactions of the six nucleotide self
      complementary sequence. Here, we introduced compensatory mutations in the self
      complementary sequence and/or a mutation in the flanking purines. We determined
      the kinetics of dimerization, the thermal stabilities and the apparent
      equilibrium dissociation constants of wild-type and mutant dimers and used
      chemical probing to obtain structural information. Our results demonstrate the
      importance of the 5'-flanking purine and of the two central bases of the self
      complementary sequence in the dimerization process. The experimental data are
      rationalized by triple interactions between these residues in the deep groove of
      the kissing helix and are incorporated into a three-dimensional model of the
      kissing loop dimer. In addition, chemical probing and molecular modeling favor
      the existence of a non-canonical interaction between the conserved adenine
      residues at the first and last positions in the DIS loop. Furthermore, we show
      that destabilization of the kissing loop complex at the DIS can be compensated by
      interactions involving sequences located downstream of the splice donor site of
      the HIV-1 genomic RNA.

PMID- 9231900
TI  - The replisome organizer (G38P) of Bacillus subtilis bacteriophage SPP1 forms
      specialized nucleoprotein complexes with two discrete distant regions of the SPP1
      genome.
AB  - Initiation of Bacillus subtilis bacteriophage SPP1 DNA replication requires the
      products of genes 38, 39 and 40 (G38P, G39P and G40P). G38P specifically binds
      two discrete regions, which are 32.1 kb apart in a linear map of the SPP1 genome.
      One of these target sites, which maps at the left end of the phage genome, within
      gene 38, was shown to function as an origin of replication and was therefore
      termed left origin (oriL). The other site, which lies within a non-coding segment
      in the late transcribed region on the right end of the genome, was termed oriR.
      Both sites contain two types of repeated elements (termed Box AB and A + T-rich
      region). The K(app) for the G38P-oriL DNA and G38P-oriR DNA complexes was
      estimated to be 1 nM and 4 nM, respectively. G38P binds to the distant oriL and
      oriR sites cooperatively. DNase I footprinting experiments showed protection by
      G38P in Box AB, but not in the A + T-rich region. Electron microscopy analysis
      showed that G38P forms a higher-order nucleoprotein structure with the SPP1 oriL
      and oriR sites through protein-protein interaction. G38P binding at its cognate
      sites does not seem to modify the length of the DNA, but to bend it. These
      results suggest that G38P forms a nucleoprotein complex on the regions where the
      SPP1 replication origins were previously predicted.

PMID- 9231902
TI  - Crystal structure of the C-terminal tetrad repeat from synexin (annexin VII) of
      Dictyostelium discoideum.
AB  - Synexin (annexin VII) is a cytosolic Ca(2+)-binding protein that promotes
      membrane fusion and forms voltage-regulated ion channels in artificial and
      natural membranes. The crystal structure of the C-terminal tetrad repeat from
      recombinant synexin (annexin VII) of Dictyostelium discoideum was solved to 2.45
      A resolution. The protein crystallized in a dimeric form with two molecules
      joined face-to-face by their convex sides. Mainly hydrogen bonds and van der
      Waals contacts are involved in dimer formation, while not Ca2+ is bound to the
      conserved Ca(2+)-binding sites. The truncated N terminus is folded into a short
      antiparallel beta-sheet, from which the side-chain of Tyr111 penetrates sideways
      into the central, hydrophilic pore and may directly affect the ion channel
      activity. In order to investigate the structure of the missing N-terminal domain,
      we synthesized a 37-membered peptide of the N-terminal tail, (GYPPQQ)6G. CD and
      NMR studies showed a random coil conformation of the peptide in solution,
      suggesting for the synexin N terminus the lack of a well-ordered, three
      dimensional fold.

PMID- 9231901
TI  - An invariant lysine residue is involved in catalysis at the 3'-5' exonuclease
      active site of eukaryotic-type DNA polymerases.
AB  - A lysine residue, contained in the motif "Kx2h", has been invariantly found in
      the eukaryotic-type (family B) class of DNA-dependent DNA polymerases with a
      proofreading function. The importance of this lysine has been assessed by site
      directed mutagenesis in the corresponding residue (Lys143) of phi29 DNA
      polymerase. Substitution of this residue either by arginine or isoleucine
      severely impaired the catalytic efficiency of the 3'-5' exonuclease activity,
      giving a characteristic distributive pattern that contrasts with the processive
      pattern displayed by the wild-type phi29 DNA polymerase. Exonuclease assays
      carried out in the presence of a DNA trap, together with direct analysis of
      enzyme/ssDNA interaction, allowed us to conclude that this altered pattern was
      due to a reduction in the catalytic rate of these mutants, but not to a weakened
      association with ssDNA. These phenotypes indicate that the lysine residue of
      motif Kx2h plays an auxiliary role in catalysis of the exonuclease reaction, in
      very good agreement with recent crystallographic data showing that the lysine
      homologue of T4 DNA polymerase is indirectly involved in metal binding at the 3'
      5' exonuclease active site. In agreement with a critical role in proofreading,
      substitution of Lys143 of phi29 DNA polymerase by arginine or isoleucine produced
      mutator enzymes that displayed a high frequency of misincorporation. Mutants at
      Lys143 also showed a reduced DNA polymerization capacity, but only when DNA
      synthesis was coupled to strand-displacement, an intrinsic property of phi29 DNA
      polymerase that is specifically affected by mutations at residues directly or
      indirectly involved in metal binding at the 3'-5' exonuclease active site.

PMID- 9231903
TI  - Hydrogen exchange in chymotrypsin inhibitor 2 probed by denaturants and
      temperature.
AB  - Hydrogen exchange of chymotrypsin inhibitor 2 has been measured in the presence
      of low concentrations of GdmCl and at different temperatures. The study of
      exchange at different temperatures allows us to obtain the activation enthalpies
      for the local exchange processes, and the change in enthalpy between the closed,
      exchange-incompetent, forms and the open, exchange-competent, forms. From the
      GdmCl dependence of exchange, an m-value, which is a measure of the new surface
      area exposed to solvent in the equilibrium between open and closed forms, can be
      determined for individual protons. This parameter therefore provides information
      about the structural nature of the opening reactions. In the absence of
      denaturant, exchange from native and native-like states dominates. As GdmCl
      concentration is increased, opening reactions that involve global unfolding are
      selectively promoted for the majority of amide protons. Three classes of protons
      emerge: for one set of protons, there is a linear and weak dependence on
      denaturant, indicating that the dominant opening reaction is the same throughout
      the range of GdmCl concentrations and involves local fluctuations with exposure
      of little new surface. For another set of protons, the most slowly exchanging
      residues, a linear, but much stronger, denaturant dependence is observed. For
      these protons, global unfolding dominates, and the m-values are similar to that
      obtained by equilibrium GdmCl denaturation measured by fluorescence under
      identical conditions. For the remaining protons, the GdmCl-dependence is weak at
      low GdmCl concentrations and increases at higher GdmCl concentrations. No segment
      of sub-global unfolding could be identified. Rather, all protons appear to merge
      together at high GdmCl concentrations to the global unfolding reaction.

PMID- 9231904
TI  - Hydrogen exchange in chymotrypsin inhibitor 2 probed by mutagenesis.
AB  - Two-dimensional NMR spectroscopy has been used to monitor hydrogen-deuterium
      exchange in chymotrypsin inhibitor 2. Application of two independent tests has
      shown that at pH 5.3 to 6.8 and 33 to 37 degrees C, exchange occurs via an EX2
      limit. Comparison of the exchange rates of a number of mutants of CI2 with those
      of wild-type identifies the pathway of exchange, whether by local breathing,
      global unfolding or a mixture of the two pathways. For a large number of
      residues, the exchange rates were unaffected by mutations which destabilized the
      protein by up to 1.9 kcal mol(-1), indicating that exchange is occurring through
      local fluctuations of the native state. A small number of residues were found for
      which the mutations had the same effect on the rate constants for exchange as on
      the equilibrium constant for unfolding, indicating that these residues exchange
      by global unfolding. These are residues that have the slowest exchange rates in
      the wild-type protein. We see no correspondence between these residues and
      residues involved in the nucleation site for the folding reaction identified by
      protein engineering studies. Rather, the exchange behaviour of CI2 is determined
      by the native structure: the most protected amide protons are located in regions
      of hydrogen bonding, specifically the C terminus of the alpha-helix and the
      centre of the beta-sheet. A number of the most slowly exchanging residues are in
      the hydrophobic core of the protein.

PMID- 9231905
TI  - The role of Glu73 of barnase in catalysis and the binding of barstar.
AB  - Barnase, a small extracellular ribonuclease from Bacillus amyloliquefaciens and
      its intracellular inhibitor barstar have co-evolved to bind tightly and rapidly.
      Barnase has also evolved to be catalytically active. The active site of barnase
      and its binding site for barstar use the same subset of amino acids. The
      exception is Glu73 (the general base in catalysis), which although located at the
      centre of the binding site, is separated by three ordered water molecules from
      barstar. We examined in this work the contribution of Glu73 to both catalysis and
      barstar binding. Truncation mutants of the general base (Glu73 --> Ala or Ser)
      retain a residual RNase activity of about 0.3% while mutants with larger
      hydrophobic replacements (Glu 73 --> Trp or Phe) have virtually no catalytic
      activity. This, and binding data of 3'-GMP with the different barnase mutants
      suggest that the loss in activity results from the elimination of the general
      base, which can be substituted to some extent by water or other polar side-chains
      in truncation mutants. All of the Glu73 mutations lead to a weakening of the free
      energy of complex formation with barstar by 1.4 to 3.0 kcal/mol (including Gln).
      This is surprising, since Glu73 does not interact directly with barstar and there
      is an electrostatic repulsion between Glu73 on barnase and the negatively charged
      binding surface of barstar. A newly developed method of constructing double
      mutant cycles between multiple mutations at the same site appears to pinpoint a
      favourable interaction between Glu73 and one of its nearest neighbours in
      barstar, Asp39. The coupling energy between those residues is presumably
      indirect: the carboxylate of Glu73 organizes neighbouring positively charged
      groups in barnase, Lys27, Arg83, and Arg87 to interact with Asp39 in barstar.
      This emphasizes that an apparent interaction between a pair of residues as
      measured with double mutant cycles is the sum of their direct and indirect
      interactions.

PMID- 9231906
TI  - Ant colonies for the travelling salesman problem.
AB  - We describe an artificial ant colony capable of solving the travelling salesman
      problem (TSP). Ants of the artificial colony are able to generate successively
      shorter feasible tours by using information accumulated in the form of a
      pheromone trail deposited on the edges of the TSP graph. Computer simulations
      demonstrate that the artificial ant colony is capable of generating good
      solutions to both symmetric and asymmetric instances of the TSP. The method is an
      example, like simulated annealing, neural networks and evolutionary computation,
      of the successful use of a natural metaphor to design an optimization algorithm.

PMID- 9231907
TI  - A quantum-theoretical approach to the phenomenon of directed mutations in
      bacteria (hypothesis).
AB  - The Darwinian paradigm of biological evolution is based on the independence of
      genetic variations from selection which occurs afterwards. However, according to
      the phenomenon of directed mutations, some genetic variations occur mostly when
      the conditions favorable for their growth are created. I propose that the
      explanation of this phenomenon should not rely on any special 'mechanism' for the
      appearance of directed mutations, but rather should be based on the principles of
      quantum theory. I consider a physical model of adaptation whereby a polarized
      photon, passing through a polarizer, changes its polarization according to the
      angle of the polarizer. This adaptation occurs by selection of the 'fitted'
      polarized state which exists as a component of superposition in the initial state
      of the photon. However, since the same state of the incoming photon should be
      decomposed differently depending on the angle of the polarizer, in this case the
      set of variations subjected to selection depends upon the selective conditions
      themselves. This reveals the crucial difference between this model of adaptation
      and canonical Darwinian selection. Based on this analogy, the capacity of a cell
      to grow in particular conditions is considered an observable of the cell; the
      plating experiments are interpreted as measurement of this observable. The only
      nontrivial suggestion of the paper states that the cell, analogously to the
      polarized photon, may be in a state of superposition of eigenfunctions of the
      operator which represents this observable, and with some probability can appear
      as a mutant upon the measurement. Alternative growth conditions correspond to the
      decomposition of the same state vector into a different superposition, consistent
      with measurement of a different observable and appearance of different mutants.
      Thus, consistent with the suggested analogy, directed mutations are explained as
      a result of random choice from the set of outcomes determined by the environment.

PMID- 9231908
TI  - Generation of fractals from incursive automata, digital diffusion and wave
      equation systems.
AB  - This paper describes modelling tools for formal systems design in the fields of
      information and physical systems. The concept and method of incursion and
      hyperincursion are first applied to the fractal machine, an hyperincursive
      cellular automata with sequential computations with exclusive or where time plays
      a central role. Simulations show the generation of fractal patterns. The
      computation is incursive, for inclusive recursion, in the sense that an automaton
      is computed at future time t + 1 as a function of its neighbouring automata at
      the present and/or past time steps but also at future time t + 1. The
      hyperincursion is an incursion when several values can be generated for each time
      step. External incursive inputs cannot be transformed to recursion. This is
      really a practical example of the final cause of Aristotle. Internal incursive
      inputs defined at the future time can be transformed to recursive inputs by self
      reference defining then a self-referential system. A particular case of self
      reference with the fractal machine shows a non deterministic hyperincursive
      field. The concepts of incursion and hyperincursion can be related to the theory
      of hypersets where a set includes itself. Secondly, the incursion is applied to
      generate fractals with different scaling symmetries. This is used to generate the
      same fractal at different scales like the box counting method for computing a
      fractal dimension. The simulation of fractals with an initial condition given by
      pictures is shown to be a process similar to a hologram. Interference of the
      pictures with some symmetry gives rise to complex patterns. This method is also
      used to generate fractal interlacing. Thirdly, it is shown that fractals can also
      be generated from digital diffusion and wave equations, that is to say from the
      modulo N of their finite difference equations with integer coefficients.

PMID- 9231909
TI  - The atomic basis of biological symmetry and periodicity.
AB  - Geometric derivations and mathematical formulas have shown how the symmetrical
      patterns of plants, animals and crystals, follow similar mathematical solutions.
      These transformations have had the great value of indicating relationships
      between different types of patterns. However, they could neither shed light on
      the material processes that led to the emergence of symmetries in nature, nor
      explain their transfer to higher levels of organization, as evolution proceeded
      from simple molecular systems to complex living organisms. Several phenomena
      contribute to elucidate the material processes that have led to the emergence and
      transfer of symmetries. Their characteristics can be summarized: (1) symmetries
      are inherent to the structure of matter, since they already occur in the
      elementary particles, such as the neutrino; (2) simple atoms, such as oxygen and
      hydrogen produce a six-ray symmetry in water crystals a pattern from which these
      crystals cannot depart; (3) the mechanism of twinning, common in minerals,
      obliges several components to associate in a regular fashion guided by the
      properties of their atoms; (4) the symmetries of crystals are decided by the
      electronic properties of their constituent atoms. Since living organisms consist
      of the same atoms that are found in the minerals, it is not surprising that the
      symmetries of the minerals were transferred intact to the cell and organism
      levels; (5) another atomic property that has been preserved is periodicity. The
      existence of the Periodic Table of the elements shows how this phenomenon is so
      well established at the atomic level. This periodicity was also transferred to
      the living organism level. Both biological structures and functions display
      periodicity; (6) the recurrence of the same type of symmetry in minerals, plant
      organs and animal structures is an expression of the preservation of this
      periodicity; (7) another manifestation of the periodicity is found in the
      recurrence of the same symmetry in flowers of a large number of plant families
      which are not closely related in evolutionary terms; (8) the re-emergence of the
      same symmetry at different levels of organization is also elucidated by the fact
      that different atom combinations can display the same form and even the same
      function. This is what has been called molecular mimicry. Examples are the
      minerals with quite different chemical compositions which display the same
      symmetry and the proteins, that although they consist of different amino acid
      sequences, result in the same structural pattern and the same function. Due to
      the occurrence of molecular mimicry, in the cell's main macromolecules, an
      organism does not even need to have the same genes to exhibit a symmetry that
      appeared long ago in evolution; and (9) support for the concept that the
      biological periodicity is anchored on the chemical periodicity is found, among
      other features, on the fact that the six atoms that build the main macromolecules
      of the cell: the nucleic acids and proteins are all simple atoms that are located
      in a 'niche' on the right side of the Periodic Table of the chemical elements.
      The basis of biological symmetry and periodicity is now starting to be elucidated
      in atomic terms.

PMID- 9231910
TI  - Reinforcement of genetic coherence: a single-locus model.
AB  - Genetic coherence and genetic separation are the outcome of evolutionary
      mechanisms which maintain genetic variation within populations through
      recombination on the one hand, and which divide this variation via speciation
      between reproductively (recombinatorically) more or less isolated populations on
      the other. While mechanisms of speciation have received considerable attention in
      biology, their counterpart, mechanisms of genetic coherence, are addressed only
      implicitly, if at all. Usually, genetic coherence is intuitively associated with
      the forces maintaining genetic polymorphisms and thus potential for flexible
      adaptational reaction of populations. However, so far no models seem to exist
      which explain the evolution of genetic coherence as the natural counterpart of
      genetic separation or speciation. In this paper a single-locus model is analyzed,
      in which a mutant allele is introduced into a resident stable diallelic
      polymorphism, and where this allele is equivalent to one of the resident alleles
      in all respects with the exception of mating relations. The conditions for
      replacement of the resident allele by its selectively equivalent mutant are
      obtained with reference to the associated mating relations. It turned out that
      for heterozygote advantage the mutant replaces the selectively equivalent
      resident allele if it increases the mating preferences for carriers of other
      alleles. The evolution of lower such preferences requires heterozygote
      inferiority, which confirms the Wallace effect of speciation (by reinforcement).
      It is argued that this observation suggests that non-selective constituents of
      the mating system form the section of the genetic system that is responsible for
      moderating the genetic load implied by adapting selection while simultaneously
      securing the adaptational potential embodied in the resident allelic variation.
      Mating systems thus serve the preservation of adaptability.

PMID- 9231911
TI  - The gene for the naevoid basal cell carcinoma syndrome acts as a tumour
      suppressor gene in medulloblastoma.
AB  - Individuals with naevoid basal cell carcinoma (Gorlin) syndrome are at increased
      risk of developing medulloblastoma in childhood. We have shown that approximately
      5% of patients with Gorlin syndrome will develop this complication in the first
      few years of life, and in addition 10% of patients with medulloblastoma diagnosed
      at age 2 years or under have Gorlin syndrome. One out of three medulloblastomas
      occurring in patients with Gorlin syndrome was shown to have lost the wild-type
      allele on 9q, indicating that the Gorlin locus probably acts as a tumour
      suppressor in the development of this tumour. We have also confirmed this role in
      a basal cell carcinoma (BCC) from the same individual. Information from these
      families would suggest that Gorlin syndrome is more common than previously
      recognized and may not always be diagnosed on clinical grounds alone even in
      middle life.

PMID- 9231912
TI  - Absence of deletions but frequent loss of expression of p16INK4 in human ovarian
      tumours.
AB  - The cyclin-dependent kinase inhibitor p16 gene (P16, MTS1, CDKN2) has been shown
      to be altered by deletion or point mutation in some human tumours and cancer cell
      lines, suggesting that it works as a tumour suppressor. We analysed p16 gene
      mutation and p16 protein expression in 42 primary ovarian carcinomas and in five
      human ovarian cancer cell lines. Polymerase chain reaction (PCR) amplifications
      of exons 1 and 2 of the gene showed no deletion or gross rearrangement in the p16
      gene. The lack of deletion was further demonstrated by Southern blot analysis.
      Looking for point mutations, we used single-strand confirmation polymorphism
      (SSCP) analysis and, in half of the tumours, we sequenced both strands of exons 1
      and 2. No mutations were detected. In 11 out of 42 patients (26%), however, we
      detected no protein expression by Western blot analysis, suggesting that
      decreased expression of p16 rather than deletion of the gene can occur in a
      significant percentage of human ovarian cancers. In the same experiment CDK4
      protein was found homogeneously expressed in all the tumour specimens and in the
      five cell lines. The lack of expression of p16 was not due to hypermethylation of
      the gene assessed by digestion of genomic DNAs with a methylation sensitive
      enzyme, suggesting that other mechanisms, not yet identified, are involved in the
      decreased expression of the p16 gene in human ovarian tumours.

PMID- 9231913
TI  - Maternal handling during pregnancy reduces DMBA-induced mammary tumorigenesis
      among female offspring.
AB  - The present study investigated whether handling of pregnant rats would affect
      mammary tumorigenesis in their female offspring. Pregnant Sprague-Dawley rats
      were injected daily with 0.05 ml of vehicle between days 14 and 20 of gestation
      or were left undisturbed. Handling did not have any effects on pregnancy or early
      development of the offspring. The female offspring were administered 10 mg of
      7,12-dimethylbenz(a)anthracene (DMBA) at the age of 55 days. The rats whose
      mothers were handled during pregnancy had a significantly reduced mammary tumour
      incidence when compared with the offspring of non-handled mothers. Thus, on week
      18 after DMBA exposure, 15% of the handled offspring had developed mammary
      tumours, whereas 44% of the non-handled offspring had tumours. No significant
      differences in the latency to tumour appearance, in the size of the tumours or in
      their growth rates were noted. Daily handling performed during post-natal days 5
      and 20 produced similar data to that obtained for prenatal handling; on week 18
      after DMBA exposure, the mammary tumour incidence among the post-natally handled
      rats was 22% and among the non-handled rats 44%. Possible deviations in hormonal
      parameters were also studied in adult female rats exposed in utero to handling.
      The onset of puberty tended to occur later among the handled offspring, but no
      differences in the uterine wet weights or serum oestradiol levels between the
      groups were noted. In conclusion, maternal handling reduced the offspring's risk
      to develop mammary tumours, and this effect was independent of the oestrogenic
      environment at adulthood. We propose that handling of a pregnant rat reduces
      mammary tumorigenesis in her offspring by means of changing the morphology of the
      mammary gland, the pattern of expression of specific genes and/or immune
      functions.

PMID- 9231914
TI  - Microsatellite instability and loss of heterozygosity in mammary carcinoma and
      its probable precursors.
AB  - Microsatellite instability is a form of genetic damage that may be due to
      defective mismatch repair genes and may be a marker of processes leading to
      malignancy. We have analysed a series of epithelial hyperplasia of usual type,
      carcinomas in situ and invasive and metastatic carcinomas from the mammary gland
      on the assumption that they represent stages in the evolution of mammary
      carcinoma. Eight markers on chromosomes 3p, 4q, 9p, 11p, 14q, 17p, 17q and Xq
      were examined for microsatellite instability and loss of heterozygosity. High
      rates of loss on chromosomes 17p, 17q and Xq indicate that these chromosomal arms
      contain genes important in mammary carcinogenesis. The rate of microsatellite
      instability observed in this study was uniformly low, irrespective of the lesion.
      This implies that microsatellite instability is not a marker of malignancy in
      most instances of mammary neoplasia.

PMID- 9231915
TI  - Constitutive production of multiple cytokines and a human chorionic gonadotrophin
      beta-subunit by a human bladder cancer cell line (KU-19-19): possible
      demonstration of totipotential differentiation.
AB  - Bladder cancer cells have been shown to secrete a variety of factors that are not
      related to cells of urothelial origin. The histogenesis of these tumour
      developments is uncertain, and a variety of theories have been previously
      reported. In the present manuscript, we identify the factors constitutively
      produced by a human bladder cancer cell line (KU-19-19) that was found to produce
      beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating
      factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8).
      The cells were obtained from a case of metastatic carcinoma that was originally
      diagnosed to be a grade 3 (WHO classification), invasive transitional cell
      carcinoma of the bladder. On microscopic observation, the cultured cells
      exhibited an epithelial appearance with vacuole formation in their cytoplasm.
      Ultrastructural observations revealed relatively marked microvilli and a tight
      junction. Significant amounts of beta-hCG, G-CSF, GM-CSF, IL-1alpha, IL-6 and IL
      8 concentrations in the supernatant from cultured cells were demonstrated by
      enzyme-linked immunosorbent assays, while the expression of mRNA of these marker
      proteins in cancer cells was also significantly exhibited by reverse
      transcription polymerase chain reaction (RT-PCR). In addition, the expression of
      G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft
      transplantability using nude mice was observed in association with the presence
      of severe neutrophilia in the peripheral blood. These results indicate that this
      cell line appears to be an effective model for the study of transitional cell
      carcinoma of the bladder with multipotent differentiation potentials.

PMID- 9231916
TI  - Fas receptor is expressed in human lung squamous cell carcinomas, whereas bcl-2
      and apoptosis are not pronounced: a preliminary report.
AB  - We report a pilot study on the Fas receptor (APO-1, CD95) in vivo in 15 human
      squamous cell (non-small) carcinomas and ten normal bronchial specimens. The
      principal aim was to investigate whether the so-called death receptor, Fas, is
      present in these tumours. Ligation of Fas promptly induces apoptosis,
      particularly in T Jurkat cells in vitro, and expression of Fas on human cancer
      would thus theoretically be of great interest. The immunoreactivity for the anti
      apoptotic protein Bcl-2 was also investigated, and the degree of apoptosis was
      evaluated by TdT dUTP nick end labelling (TUNEL) and conventional morphological
      criteria. Fas was present in all initial tumours but absent in control tissue,
      that is in the potential precursor cells of bronchial epithelium (P = 0.001). Fas
      was not detectable after radiotherapy (P = 0.03). We propose that radiotherapy
      induces an early selection of tumour cells rather than a down-regulation of Fas.
      Both Bcl-2 and apoptosis (TUNEL) were generally expressed at a modest level. In
      agreement with other studies, we did not find any significant correlation between
      Bcl-2 and prognosis, or between Bcl-2 and TUNEL. Hence, in this preliminary
      report, we have demonstrated Fas receptor in human squamous cell carcinomas in
      vivo. This is a novel finding, and the apparent absence of Fas after radiotherapy
      may have important therapeutic implications.

PMID- 9231917
TI  - Apoptosis and 1-methyl-2-nitroimidazole toxicity in CHO cells.
AB  - The time course and characteristics of the selective hypoxic cytotoxicity of the
      2-nitroimidazole model compound 1-methyl-2-nitroimidazole (INO2) were analysed
      during prolonged time periods (up to 5 days post treatment). When control
      populations were seeded at the same cell density as drug-treated cells, they
      entered confluency at day 3 and underwent apoptosis at day 5, which appeared to
      be mediated by an autocrine mechanism. In subsequent studies of drug-treated
      cells, the seeding density of treated cells was adjusted to avoid this cell
      confluency effect. Treatment with a low INO2 concentration (2.5 mM) resulted in
      apoptotic DNA fragmentation (ladders), which was observed 4-5 days after an acute
      6-h hypoxic drug exposure. In contrast, at a high INO2 concentration (40 mM) for
      2 h, which was equitoxic to the low concentration, no characteristic DNA ladders
      were observed. Fluorescence microscopy revealed apoptotic bodies and pyknotic
      nuclei 5 days following hypoxic 2.5 mM INO2 exposure, whereas 40 mM INO2 hypoxic
      treatment produced cellular ghosts devoid of DNA 5 days after exposure,
      consistent with the DNA ladder results. However, characteristic apoptotic
      morphology was previously observed immediately after the acute hypoxic exposure
      of 40 mM INO2. Cell cycle analysis and DNA fragmentation as measured by the TdT
      assay suggested that dose-dependent differences in the apoptotic response occur
      post exposure after an equitoxic acute hypoxic exposure to either the low or the
      high INO2 concentration. This dose-dependent differential in response may be
      attributed to the degree of initial DNA damage as measured by the comet assay.

PMID- 9231918
TI  - Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head
      and neck squamous cell carcinoma cell lines.
AB  - Retinoids can reverse potentially premalignant lesions and prevent second primary
      tumours in patients with head and neck squamous cell carcinoma (HNSCC).
      Furthermore, it has been reported that acquired resistance to all-trans retinoic
      acid (RA) in leukaemia is associated with decreased plasma peak levels, probably
      the result of enhanced retinoid metabolism. The aim of this study was to
      investigate the metabolism of retinoids and relate this to growth inhibition in
      HNSCC. Three HNSCC cell lines were selected on the basis of a large variation in
      the all-trans RA-induced growth inhibition. Cells were exposed to 9.5 nM
      (radioactive) for 4 and 24 h, and to 1 and 10 microM (nonradioactive) all-trans
      RA for 4, 24, 48 and 72 h, and medium and cells were analysed for retinoid
      metabolites. At all concentrations studied, the amount of growth inhibition was
      proportional to the extent at which all-trans-, 13- and 9-cis RA disappeared from
      the medium as well as from the cells. This turnover process coincided with the
      formation of a group of as yet unidentified polar retinoid metabolites. The level
      of mRNA of cellular RA-binding protein II (CRABP-II), involved in retinoid
      homeostasis, was inversely proportional to growth inhibition. These findings
      indicate that for HNSCC retinoid metabolism may be associated with growth
      inhibition.

PMID- 9231919
TI  - Reversion of multidrug resistance with polyalkylcyanoacrylate nanoparticles:
      towards a mechanism of action.
AB  - Polyalkylcyanoacrylate (PACA) nanoparticles loaded with doxorubicin allowed
      multidrug resistance to be overcome in vitro. However, increased cytotoxicity is
      not always correlated with an increased level of intracellular drug. Although we
      have previously shown that PACA nanoparticles are not endocytosed by tumour
      cells, we report here that a direct interaction between nanoparticles and cells
      is a necessary requirement for overcoming resistance. In addition, the results
      showed that the degradation products of PACA (mainly polycyanoacrylic acid) in
      the presence of doxorubicin are able to increase both accumulation and
      cytotoxicity, thus suggesting the formation of a doxorubicin-polycyanoacrylic
      acid ion pair. It is therefore concluded that resistance is overcome as a result
      of both the adsorption of nanoparticles to the cell surface and increased
      doxorubicin diffusion by the accumulation of an ion pair at the plasma membrane.

PMID- 9231920
TI  - Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced
      cytotoxicity on bladder cancer cells.
AB  - This study was undertaken to investigate the intracellular induction of reactive
      oxygen species (ROS) by cis-dichlorodiammineplatinum (CDDP) and the augmentation
      of their cytotoxicity in bladder cancer cells (KU7) by enhancement of ROS
      generation by the glutathione (GSH) depletors buthionine sulphoximine (BSO) and
      diethylmaleate (DEM). CDDP-induced cytotoxicity in KU7 cells and its modulation
      by GSH depletors were determined using spectrophotometric measurement with
      crystal violet staining. The effects of GSH depletors on intracellular GSH levels
      were confirmed using the GSH reductase-DTNB recycling method. Intracellular ROS
      generation induced by CDDP with or without GSH depletors was estimated from the
      amount of intracellular dichlorofluorescein (DCF), an oxidized product of
      dichlorofluorescein (DCFH), which was measured with an anchored cell analysis and
      sorting system. The cytotoxic effects of CDDP (IC50 15.0 +/- 2.5 microM) were
      significantly enhanced by BSO (IC50 9.3 +/- 2.6 microM, P < 0.01) and DEM (IC50
      10.3 +/- 0.3 microM, P <0.01). BSO and DEM produced a significant depletion in
      intracellular GSH levels (9.6 +/- 0.4 nmol 10(-6) cells, 17.9 +/- 1.0 nmol 10(-6)
      cells) compared with the controls (30.5 +/- 0.6 nmol 10(-6) cells). Intracellular
      DCF production in KU7 cells treated with CDDP (1.35 +/- 0.33 microM) was
      significantly enhanced by the addition of BSO (4.43 +/- 0.33 microM) or DEM (3.12
      +/- 0.22 microM) at 150 min. These results suggest that ROS may play a
      substantial role in CDDP-induced cytotoxicity and that GSH depletors augment its
      cytotoxicity through an enhancement of ROS generation in bladder cancer cells.

PMID- 9231921
TI  - Cytotoxic activity of topotecan in human tumour cell lines and primary cultures
      of human tumour cells from patients.
AB  - The cytotoxic activity and cross-resistance pattern of the novel topoisomerase I
      inhibitor topotecan (Topo) were investigated in ten cell lines, representing
      different mechanisms of cytotoxic drug resistance, and in 218 fresh human tumour
      samples using the fluorometric microculture cytotoxicity assay (FMCA). Resistance
      to Topo in the cell lines was associated with expression of the multidrug
      resistance-associated protein (MRP), whereas the cell lines with P-glycoprotein
      (P-gp), topoisomerase II and glutathione-associated resistance did not show
      decreased sensitivity to the drug. Topo was more active in haematological than in
      solid tumour samples, but substantial activity was observed in carcinomas of the
      ovary and breast, sarcoma and childhood solid tumours. Cross-resistance to
      standard drugs representing different mechanisms of action was generally low in
      patient cells. The effect of Topo was better after longer exposure, but this time
      dependent effect was largely abolished when adjustment for in vitro exposure was
      made. Topo showed activity both in proliferative and non-proliferative cell
      systems. The results indicate that Topo is insensitive to major mechanisms of
      resistance except for MRP. Proliferation does not seem to be necessary for the
      effect of Topo, and no superiority for protracted dosing schedules was observed.
      The results also suggest that, for example, leukaemias, lymphomas, sarcomas and
      childhood solid tumours may be suitable targets for future phase II trials.

PMID- 9231922
TI  - Comparison of radiobiological effective depths in 65-MeV modulated proton beams.
AB  - To assess the achievement of uniformity of radiobiological effectiveness at
      different depths in the proton spread-out Bragg peak (SOBP), Chinese hamster
      ovary (CHO) cells were exposed to 65-MeV modulated proton beams at the Research
      Center for Nuclear Physics (RCNP) of Osaka University. We selected four different
      irradiation positions: 2 mm depth, corresponding to the entrance, and 10, 18 and
      23 mm depths, corresponding to different positions in the SOBP. Cell survival
      curves were generated with the in vitro colony formation method and fitted to the
      linear-quadratic model. With 137Cs gamma-rays as the reference irradiation, the
      relative biological effectiveness (RBE) values for a surviving fraction (SF)
      level of 0.1 are 1.05, 1.10, 1.12 and 1.19 for depths of 2, 10, 18 and 23 mm
      respectively. A significant difference was found between the survival curves at
      10 and 23 mm (P < 0.05), but not between 18 and 10 mm or between 18 and 23 mm.
      There was a significant dependence of RBE on depths in modulated proton beams at
      the 0.1 surviving fraction level (P < 0.05). Moreover, the rise of RBEs
      significantly depended on increasing SF level or decreased approximately in
      correspondence with irradiation dose (P = 0.0001). To maintain uniformity of
      radiobiological effectiveness for the target volume, careful attention should be
      paid to the influence of depth of beam and irradiation dose.

PMID- 9231923
TI  - 3-[211At]astato-4-fluorobenzylguanidine: a potential therapeutic agent with
      prolonged retention by neuroblastoma cells.
AB  - An analogue of meta-iodobenzylguanidine (MIBG) in which an aromatic hydrogen was
      replaced with fluorine has been found to possess many properties similar to those
      of the parent compound. Moreover, 4-fluoro-3-iodobenzylguanidine (FIBG) was
      retained in vitro by human neuroblastoma cells to a much greater extent than MIBG
      itself. Since alpha-emitters such as 211At could be valuable for the treatment of
      micrometastatic disease, an FIBG analogue in which the iodine atom is replaced by
      211At would be of interest. In this study, we have evaluated the in vitro and in
      vivo properties of 3-[211At]astato-4-fluorobenzylguanidine ([211At]AFBG). The
      specific binding of [211At]AFBG to SK-N-SH human neuroblastoma cells remained
      fairly constant over 2- to 3-log activity range and was similar to that of
      [131I]MIBG. The uptake of [211At]AFBG by this cell line was reduced by
      desipramine, ouabain, 4 degrees C incubation, noradrenaline, unlabelled MIBG and
      FIBG, suggesting that its uptake is specifically mediated through an active
      uptake-1 mechanism. Over the 16 h period studied, the amount of [211At]AFBG
      retained was similar to that of [131I]FIBG, whereas the per cent of retained meta
      [211At]astatobenzylguanidine ([211At]MABG) was considerably less than that of
      [131I]FIBG (53% vs 75%; P < 0.05). The IC50 values for the inhibition of uptake
      of [131I]MIBG, [211At]MABG, [125I]FIBG and [211At]AFBG by unlabelled MIBG were
      209, 300, 407 and 661 nM respectively, suggesting that the affinities of these
      tracers for the noradrenaline transporter in SK-N-SH cells increase in that
      order. Compared with [211At]MABG, higher uptake of [211At]AFBG was seen in vivo
      in normal mouse target tissues such as heart and, to a certain extent, in
      adrenals. That the uptake of [211At]AFBG in these tissues was related to the
      uptake-1 mechanism was demonstrated by its reduction when mice were pretreated
      with desipramine. However, the stability of [211At]AFBG towards in vivo
      dehalogenation was less than that of [211At]MABG, as evidenced by the higher
      uptake of 211At in thyroid, spleen, lungs and stomach.

PMID- 9231924
TI  - Stereologically estimated mean nuclear volume of prostatic cancer is a reliable
      prognostic parameter.
AB  - Although different histological grading systems of prostatic cancer refer to well
      described characteristics, results are hard to reproduce. The aim of this study
      was to obtain morphometric data that would enable objective and reproducible
      grading of prostatic cancers by stereological estimation of mean nuclear volume
      (MNV). The clinical records and tissue specimens from 100 patients who were newly
      diagnosed as having prostatic cancer from 1973 to 1990 and who were followed up
      for 5 years or longer were retrospectively examined. We analysed the relationship
      between MNV and clinical stage, Gleason score and histological grading according
      to the World Health Organization (WHO) classification. To evaluate prognostic
      predictors, a multivariate analysis of factors associated with cause-specific
      survival was performed. We found a good correlation between the MNV and clinical
      stage and between the MNV and histological grading. There was no correlation
      between MNVs and Gleason scores. Multivariate analysis revealed that the MNV was
      the only predictor of survival time (coefficient 0.005; P < 0.0001; hazard ratio
      1.005). We consider that the MNV is an excellent predictor of the prognosis in
      patients with prostatic cancer. Moreover, stereological estimation of MNV is a
      simple, quick, inexpensive and reliable morphometric procedure that enables the
      quantitative analysis of the histological and biological character of prostatic
      cancer.

PMID- 9231925
TI  - Elevated levels of the angiogenic cytokines basic fibroblast growth factor and
      vascular endothelial growth factor in sera of cancer patients.
AB  - The concentration of basic fibroblast growth factor (bFGF) and vascular
      endothelial growth factor (VEGF) was determined in the serum of 90 untreated and
      42 treated metastatic cancer patients, including patients with colorectal,
      breast, ovarian and renal carcinomas, with an enzyme-linked immunosorbent assay
      (ELISA). Levels higher than the 95th percentile of the concentrations of a
      control group, i.e. 7.5 pg ml(-1) for bFGF and 500 pg ml(-1) for VEGF, were
      identified as 'elevated'. One measurement during follow-up was included into the
      analysis per patient. For 19 treated patients, consecutive serum samples were
      analysed. Fifty-seven per cent of all untreated patients had elevated serum
      levels of one or both angiogenic factors. The fraction of patients with elevated
      serum levels of bFGF and/or VEGF was similar in the different tumour types.
      Agreement of bFGF levels and VEGF levels, classified in relation to their
      respective cut-off values, was present in 67% of all patients. Fifty-eight per
      cent of the patients with progressive disease during treatment compared with 15%
      of the patients showing response to treatment (chi-squared test P < 0.05) had
      elevated bFGF and/or VEGF serum levels. When consecutive serum samples were
      analysed, two-thirds of the patients showing progressive disease had increasing
      serum levels of the angiogenic factors compared with less than one-tenth of the
      patients showing response (chi-squared test P < 0.05). The lack of association
      between the serum bFGF and VEGF levels and the tumour type may suggest an
      aspecific host reaction responsible for solid tumour-related angiogenesis. The
      main determinants of the serum bFGF and VEGF concentration are the progression
      kinetics of the metastatic carcinomas.

PMID- 9231926
TI  - Elevated urinary transforming growth factor-beta1 level as a tumour marker and
      predictor of poor survival in cirrhotic hepatocellular carcinoma.
AB  - To assess the clinical relevance of transforming growth factor-beta1 (TGF-beta1)
      in hepatocellular carcinoma (HCC), urinary TGF-beta1 and serum alpha-fetoprotein
      (AFP) were determined in 94 patients with cirrhotic HCC, 94 age- and sex-matched
      patients with cirrhosis alone and 50 healthy adults. TGF-beta1 level in HCC was
      higher than in cirrhosis alone or in healthy controls (each P = 0.0001). There is
      an inverse correlation between TGF-beta1 and AFP levels (r = -0.292, P = 0.004).
      Significantly higher TGF-beta1 level was found in HCC patients with worsening
      Child-Pugh stages, diffuse HCC, tumour size > 3 cm, multilobular tumour and AFP <
      or = 20 ng ml(-1). TGF-beta1 level decreased after complete treatment with
      transcatheter arterial chemoembolization (P = 0.0001). The median survival in HCC
      patients with raised TGF-beta1 was shorter than those with normal TGF-beta1 (P =
      0.018). Multivariate analysis indicated that TGF-beta1 and AFP were significantly
      correlated with the presence of HCC. In addition, TGF-beta1 could be used as a
      diagnostic marker for HCC, particularly in tumours with low AFP production. In
      conclusion, elevated urinary TGF-beta1 level is a tumour marker and predictor of
      poor survival for cirrhotic HCC.

PMID- 9231927
TI  - Physical and psychosocial outcomes in cancer patients: a comparison of different
      age groups.
AB  - In a cross-sectional study, we investigated the relationship between age,
      physical health, social and economic resources, functional status, activities of
      daily living (ADL) and disease-related variables of 227 patients with cancer.
      Using multidimensional outcome measures we examined age differences in three age
      groups (< 45, 46-65, > 65 years) and identified predictors of performing ADL. The
      results indicated that older patients have outcomes similar to those of younger
      patients. There were no significant differences in quality of life, performance
      status and physical health among the three age groups. The only areas where age
      related differences were found were co-morbidity and cancer-related impairments.
      Patients aged 45-65 years and patients 65 years and older reported a higher level
      of co-morbidity and more cancer-related impairments than those aged 45 and
      younger. Although older patients had higher co-morbidity, they showed similar
      Karnofsky Performance Status (KPS) scores to those of their younger counterparts.
      The regression analysis revealed social resources, self-reported health,
      performance status and complexity of care as significant predictors of patients'
      ADL, but not age, co-morbidity or severity of treatment. The findings support the
      conclusion that differences in performing ADL between younger and older patients
      with cancer are minimal and tend to be due to co-morbidity. Thus, treatment
      should be decided by a patient's physical health rather than by age.

PMID- 9231928
TI  - Cerebral metastases of cutaneous melanoma.
AB  - Cerebral metastases of cutaneous melanoma carry a very poor prognosis. We report
      our experience of 31 patients who presented with cerebral metastasis of cutaneous
      melanoma in a 5-year period between mid-1991 and mid-1996. Cerebral metastases
      were diagnosed on computerized tomography (CT) scan after patients became
      symptomatic. The overall median survival in our series was 4 months. Seventeen
      patients (55%) received treatment with radiotherapy and dexamethasone with
      resolution of their symptoms, although median survival remained at 4 months. Six
      patients (19%) had surgery followed by whole brain radiotherapy, with median
      survival of 5 months. The remaining eight patients received dexamethasone alone.
      Data from patients surviving less than 2 months and over 6 months suggest that
      the poor prognostic factors are the presence of more than one cerebral metastasis
      and additional extracranial metastases.

PMID- 9231929
TI  - Carbogen and nicotinamide in the treatment of bladder cancer with radical
      radiotherapy.
AB  - Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia
      modifying agents during radical radiotherapy for bladder cancer using a standard
      daily 20-fraction schedule. Three groups of patients have received (a)
      nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in
      20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4
      weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4
      weeks. Ten patients were treated in each group. All patients completed carbogen
      and radiotherapy as prescribed, but only 45% completed daily nicotinamide over
      the 4-week treatment period. The end points of this study were acute bowel and
      bladder morbidity and local control at cystoscopy 6 months after treatment. An
      expected level of acute bowel and bladder morbidity was seen that reverted to
      normal in most patients by 12 weeks with no difference between the three
      treatment groups. Complete response rates at 6 months were seven out of ten
      (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen
      alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It
      is concluded that carbogen and nicotinamide may improve the results of daily
      fractionated radiotherapy in bladder cancer and that further evaluation is
      required.

PMID- 9231930
TI  - Phase II trial of raltitrexed ('Tomudex') in advanced small-cell lung cancer.
AB  - Raltitrexed, a thymidylate synthase inhibitor, was given to 21 patients with
      advanced small-cell lung cancer, at a dose of 3 mg m(-2) as a 15-min intravenous
      infusion at 21-day intervals. All of the patients had extensive disease and 17
      had received prior therapy. Patients with disease refractory to primary
      chemotherapy were excluded. Forty-one treatment cycles were given (median two,
      range one to four). The drug was well tolerated. No objective tumour response was
      documented. The patients had chemoresistant disease, as shown by a response in
      only one of ten patients who went on to receive alternative cytotoxic regimens.
      We conclude that raltitrexed given in this schedule is inactive as second line
      therapy for small-cell lung cancer.

PMID- 9231931
TI  - Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD)
      plus interferon alpha for metastatic melanoma: a multicentre phase II study.
AB  - High response rates in patients with metastatic melanoma have been achieved with
      combination chemoimmunotherapy. A response rate of 62% in 45 patients has been
      reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD)
      plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to
      confirm these results. Melanoma patients with distant metastases were treated as
      outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on
      days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on
      day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU
      daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the
      study. The median number of metastatic sites was three (range 1-5), and 81% of
      patients had visceral metastases. Nine patients had brain metastases, and seven
      patients were systemically pretreated. Among the 41 patients that were evaluable
      for response, the response rate was 27% (95% CI 14-3%), with one complete and ten
      partial remissions. The response rate in 25 previously untreated patients without
      brain metastases was 40% (95% CI 21-61%). Median duration of response was 6
      (range 2-14+) months; median overall survival was 5 (1-26) months. The main
      toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in
      metastatic melanoma. The lower response rate in our study compared with the
      previous report is probably related to patient selection, as in the previous
      study 46% of patients had stage III disease, whereas all our patients had stage
      IV disease, which is associated with a worse prognosis.

PMID- 9231933
TI  - Prognostic factors in gastric carcinoma.

PMID- 9231934
TI  - Physiological pacing for elderly patients: exploit the benefits but don't overdo
      it.

PMID- 9231932
TI  - Comparison of toremifene and tamoxifen in post-menopausal patients with advanced
      breast cancer: a randomized double-blind, the 'nordic' phase III study.
AB  - The study was planned to compare, in a prospective double-blind randomized trial,
      the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post
      menopausal patients with advanced breast cancer who have not had prior systemic
      therapy for advanced disease. Four hundred and fifteen post-menopausal patients
      with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were
      randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients
      were stratified to measurable and non-measurable but evaluable groups. They were
      assessed for response to therapy, time to progression (TTP), time to treatment
      failure (TTF), response duration, overall survival and drug toxicity. Two hundred
      and fourteen patients were randomized into TOR and 201 into TAM treatment. The
      response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P =
      0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to
      3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047).
      The 95% CI for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR
      patients (9.8%) and the TAM patients (18.9%) discontinued the treatment
      prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3
      vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89
      and the subsequent 95% CI 0.73-1.09. The median overall survival was 33.0 months
      for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95%
      CI of 0.73-1.22. The transient difference in TTP may be related to an imbalance
      in ER content of the tumours. When only patients with ER-positive tumours were
      considered (n = 238), no difference between two treatments was seen (P = 0.578).
      TAM was associated with an overall slightly higher frequency of adverse drug
      reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these
      events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and
      cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In
      conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and
      safe in the treatment of advanced post-menopausal ER-positive or ER-unknown
      breast cancer.

PMID- 9231935
TI  - Late-onset Huntington's disease: a clinical and molecular study.
AB  - Using the Huntington's disease register for South Wales, a total of 86 affected
      individuals were identified living in the counties of Mid Glamorgan, South
      Glamorgan and Gwent, giving a point prevalence rate for Huntington's Disease in
      South East Wales of 6.2/100,000. Only four (4.7%) of these individuals developed
      their symptoms after the age of 60 years. A subsequent retrospective search of
      the register identified a total of 33 individuals with clinical evidence of
      Huntington's disease and whose age of onset of symptoms occurred between the ages
      of 60 and 77 years. In this group the median time for disease duration from the
      onset of symptoms was 13 years (range 0.5-25 years), with survival up to age 86
      years recorded. Initial symptoms of Huntington's disease included disturbance of
      gait in 32 individuals; 31 had involuntary movements, and 20 had abnormality of
      speech. Major psychiatric symptoms were present in only six cases; but
      approximately a third (ten cases) had symptoms related to impaired cognitive
      function. Molecular analysis was possible on ten individuals in the series. The
      expanded CAG repeat sequence in the Huntington's disease gene was found in all
      cases, with a narrow range of 36-38 repeats, representing the smallest repeats
      seen in our Huntington's disease group. Our study suggests that Huntington's
      disease in elderly people causes predominantly motor disturbance at onset with
      relatively mild disability and a favourable outlook for both independent living
      and for life expectancy. However, the potential for under-diagnosis in this age
      group may have considerable genetic consequences, with transmission of the
      disorder to numerous descendants by the time its hereditary nature is recognized.

PMID- 9231936
TI  - Translation of clinical and neuropsychological instruments into French: the CERAD
      experience.
AB  - The increasing number of international and epidemiological studies of Alzheimer's
      disease points to the need for linguistically equivalent translations of measures
      for identifying the presence, types, and severity of dementia in cross-cultural
      populations. In translating the CERAD (Consortium to Establish a Registry for
      Alzheimer's Disease) neuropsychological instruments into French, several
      linguistic issues have emerged such as semantic, phonetic, and word-frequency
      equivalences. In verbal memory tests, these problems, though minor in appearance,
      can be major pitfalls in studies comparing cognitive function in populations
      differing in language. Description of the translation procedure and examples of
      problems encountered are presented, with measures taken to resolve them.

PMID- 9231937
TI  - Age-associated differences in sensori-motor function and balance in community
      dwelling women.
AB  - Tests of visual, vestibular, sensori-motor and balance function were administered
      to 550 women, aged between 20 and 99 years at a Balance and Gait Laboratory. All
      of the sensory, motor and balance system measures showed significant age
      associated differences. Multiple regression analyses revealed that the measures
      of lower limb sensation were the consistent sensori-motor factors contributing to
      balance under normal conditions (standing on a firm surface with eyes open or
      closed). Under more challenging conditions (standing on foam with eyes open)
      vision, strength and reaction time played significant roles, whilst when standing
      on foam with eyes closed, vestibular function also made a significant
      contribution. Analysis of percentage increases in sway under conditions where
      visual and peripheral sensation systems were removed or diminished, compared with
      sway under optimal conditions, indicated that up until age 65 there was an
      increased reliance on vision for balance control. Beyond this age, the
      contribution made by vision declined, so that in the oldest age-groups reduced
      vision was less able to supplement peripheral input, resulting in increased sway
      areas. Peripheral sensation however was the most important sensory system in the
      maintenance of static postural stability at all ages.

PMID- 9231938
TI  - Screening for anxiety and depression in elderly medical outpatients.
AB  - In a study of 45 consecutive new outpatients at geriatric medicine clinics, 17.8%
      were diagnosed as depressed and 2.2% as anxious using the Geriatric Mental Status
      Schedule. Of two screening instruments, the Geriatric Depression Scale (GDS), in
      either 30-item or 15-item version, performed well and the depression sub-scale of
      Goldberg and Bridges' screening questionnaire for depression and anxiety in
      medical settings was adequate. The anxiety sub-scale of the latter was poor.
      Detection by geriatricians of depression and anxiety disorders was poor. It is
      recommended that a short screening instrument for the detection of depression,
      such as the GDS, be incorporated into the clinic setting. As yet there is no
      satisfactory screening questionnaire for detecting anxiety disorders.

PMID- 9231939
TI  - The prevalence of depression in geriatric medical outpatients.
AB  - One hundred and fifty-nine patients attending a geriatric medical outpatient
      clinic were screened for depression using the geriatric depression scale (GDS)
      and brief assessment schedule depression cards (BASDEC). Twenty-two (13.8%)
      patients screened positive with one or other test, 13 (8.2%) being positive with
      both screening tests. There was a highly significant correlation between the two
      screening tests but the BASDEC instrument was quicker and easier to administer.
      Eighteen of 22 patients who screened as positive proved to have clinical
      depression. On subsequent re-testing of 17 of these patients 4-6 weeks later,
      eight were still positive, but nine patients were now negative and subjectively
      felt better. These findings suggest the possibility of a transient mood
      disturbance occurring in elderly patients akin to recurrent brief depression seen
      in younger subjects, and have implications for starting therapy in apparently
      depressed elderly people.

PMID- 9231940
TI  - Aluminium in antacids and cooking pots and the risk of hip fractures in elderly
      people.
AB  - The relationship between hip fractures and aluminium in antacids and cooking pots
      was examined in an epidemiological study in Sydney, Australia. A population-based
      case-control study was conducted and 416 men and women aged 65 years and over
      were recruited (209 cases and 207 controls). There was a significantly (p < 0.05)
      increased risk of hip fracture associated with use of aluminium cooking pots at
      age 20 years: the age- and sex-adjusted odds ratio was 1.9 [95% confidence
      interval (CI) 1.1-3.2]. No association was detected between risk of hip fracture
      and current use of aluminium cooking pots or use at age 50. There was some
      suggestion that long-term use of aluminium-containing antacids might increase the
      risk of hip fracture: the adjusted odds ratio comparing those who had used
      aluminium-containing antacids for more than 10 years with those who had never
      used them was 1.8 (95% CI 0.8-4.1). The findings of this study support the need
      for further research on the association between oral ingestion of aluminium and
      risk of hip fracture.

PMID- 9231942
TI  - Seasonal variation in 25-hydroxyvitamin D and parathyroid hormone concentrations
      in healthy elderly people.
AB  - Seasonal variation in serum 25-hydroxyvitamin D and parathyroid hormone
      concentration was examined longitudinally in 96 community-dwelling men and women
      aged 65-74 years. Mean 25-hydroxyvitamin D concentration was lowest in winter
      (22.7 mmol/l) and highest in summer (35.4 mmol/l); mean parathyroid hormone
      concentration was highest in winter (3.55 pmol/l) and lowest in summer (3.24
      pmol/l): these seasonal variations were highly significant (p < 0.0001).
      Parathyroid hormone concentrations were inversely related to 25-hydroxyvitamin D
      concentrations (p < 0.0001). Seasonal variation of 25-hydroxyvitamin D and
      parathyroid hormone concentration is marked in older healthy adults in Britain.
      Even in summer, mean 25-hydroxyvitamin D concentrations are low; maintaining more
      optimal vitamin D levels in the general population may have clinical and public
      health benefits.

PMID- 9231941
TI  - Spectral analysis of heart rate variability in evaluation of sympathetic function
      in elderly subjects.
AB  - Plasma concentration of noradrenaline is often used as a measure of sympathetic
      nervous activity. Recently, the method of spectral analysis of heart rate
      variability has been introduced to detect autonomic dysfunction. To examine
      whether spectral analysis of heart rate variability is useful in evaluating
      sympathetic function, changes in the heart rate variability in the low-frequency
      spectral band were compared with the change of plasma noradrenaline in response
      to head-up tilt in elderly hypertensives (n = 13) and diabetics (n = 13). In
      hypertensive subjects, there was an increase in relative low-frequency power (p =
      0.015) and an increase in plasma noradrenaline level (p = 0.040) in response to
      head-up tilt. Diabetics did not show corresponding changes. There was no change
      in absolute low-frequency power in either group. It is concluded that spectral
      analysis of heart rate variability can be useful in evaluating sympathetic
      function in elderly subjects.

PMID- 9231943
TI  - The development of a care-giving burden scale.
AB  - A burden scale is described that is conceptually specific by concentrating on an
      assessment of different aspects of distress of care-giving burden and
      conceptually sensitive by distinguishing two dimensions: the relationship of the
      carer and the care-receiver and the limitations in the personal life of the
      carer. To develop a burden scale an analysis was carried out on a database of an
      intervention study in which 89 informal caregivers of psychogeriatric patients
      were interviewed twice. A principal components analysis was carried out showing
      two main factors that could be interpreted as the two dimensions mentioned above.
      Reliability analysis showed a Cronbach's alpha of 0.84 for the total care-giving
      burden scale (13 items) and 0.77 for both subscales (7 and 6 items), confirmed in
      an independent sample. An analysis of the hierarchy of items (Mokken Scale
      Analysis) showed a strong and moderate hierarchy for the subscales and the total
      scale, respectively. Finally, an analysis of construct validity showed strong
      correlations of care-giving burden with depression of the carer and deviant
      behaviour of the patient.

PMID- 9231944
TI  - Evaluation of a clinical score for prognostic stratification of elderly stroke
      patients.
AB  - Orpington Prognostic Score (OPS) is a clinically derived score which incorporates
      measures of motor deficit, proprioception, balance and cognition. OPS and urinary
      continence were measured prospectively in 217 stroke survivors over 75 years of
      age at 1, 2 and 4 weeks after stroke and were correlated with dependence at
      discharge. Three levels of dependence were defined based on personal self-care
      abilities. OPS ranged from 2.0 to 3.2 (median 2.8) at 2 weeks after stroke in
      patients independent at discharge (n = 54). Their initial median Barthel index of
      4 improved by a median of 12. Urinary continence was achieved in 95% of these
      patients by 2 weeks. All patients were discharged home, 39 (72%) within 4 weeks.
      Patients with limited dependence at discharge (n = 129) had OPS of 3.2-4.8
      (median 4.0) at 2 weeks. Two-thirds were continent at 2 weeks. Their initial
      median Barthel index was 2 and changed by a median of 12. Seventy-one (55%) of
      these patients went home. OPS ranged from 5.2 to 6.8 (median 6.0) at 2 weeks in
      patients dependent at discharge (n = 34). About 20% of these patients were
      continent. Their initial median Barthel index of 2 improved by a median of 6 at
      discharge. Only five (15%) patients in this group went home. OPS was comparable
      with urinary incontinence for sensitivity (96% vs. 90%), specificity (36% vs.
      39%) and accuracy (75% vs. 66%) in identifying stroke patients achieving
      independent living. OPS had a greater predictive value than urinary incontinence
      in identifying patients requiring institutional care (82% vs. 57%). OPS is a
      simple objective predictor of outcome in elderly stroke patients, suitable for
      everyday clinical use. It also can facilitate stroke research by identifying a
      'middle group' of patients who would be most sensitive to changes in therapy or
      organization of stroke services.

PMID- 9231945
TI  - Predictors of nursing home placement and mortality of residents in intermediate
      care.
AB  - Assessments of sensorimotor function, cognitive status and health measures were
      made in 95 intermediate-care (hostel) residents (mean age 82.7 years). The
      residents were then followed up for 3 years to determine which measures were
      associated with nursing-home placement and/or death. Information on the outcome
      of 92 participants was available at the end of the 3-year period. At this time,
      53 residents (58%) were still residing at the hostel, seven (8%) had been
      transferred to nursing homes and 32 residents (35%) had died. Sixteen of the 32
      subjects who had died had been transferred to nursing homes. Discriminant
      function analysis identified tactile sensitivity, ankle dorsiflexion strength,
      reaction time, sway with eyes open on a compliant (foam rubber) surface and
      cognitive impairment as the variables that significantly discriminated between
      subjects who were still in intermediate care and subjects who had been
      transferred to nursing homes. This procedure correctly classified 88% of subjects
      into intermediate care or nursing home groups. These variables, with the
      exception of ankle dorsiflexion strength, were also included in the final
      discriminant model when predicting mortality, correctly classifying 71% of the
      subjects. The findings indicate that cognitive impairment and reduced functioning
      in a number of sensorimotor factors are strongly related to poor outcomes for
      residents in hostel care.

PMID- 9231946
TI  - Changes over time in the ADL status of elderly US veterans.
AB  - The ageing of the US veteran population has greatly out-paced that of the general
      US population in the last decade and the demographics of this subgroup have
      changed relative to the US general population. To address the concerns of policy
      makers within the US Department of Veterans' Affairs (VA), data on elderly US
      male veterans and non-veterans from the Longitudinal Survey on Aging in 1984,
      1986, 1988, and 1990 were used in a prospective study. Health status or well
      being was assessed through changes over time in ADL status, according to the
      following five categories; (I) the presence of no ADL dependence and not
      developing a dependence between survey periods, (II) no change in ADL dependence
      between survey periods, (III) an increase in ADL dependence status between survey
      periods, (IV) a decrease in ADL dependence between survey periods, and (V) the
      occurrence of death between survey periods. Using a polytomous logistic
      regression model, these five categories were assessed in relation to a set of
      variables representing social, health-care utilization, and socioeconomic
      characteristics. The estimated coefficients from the model indicate that family
      income, having worked in the last 12 months, having an increase or no change in
      levels of physical activity in the past 12 months and the presence of Medicare
      coverage are inversely associated with moving, over time, into a lower state of
      health status or well-being. The prior existence of an ADL limitation, the number
      of doctor and hospital visits in the past 12 months, level of education, having
      been widowed in the past 12 months and veteran status were all proportionally
      associated with the likelihood of moving into a lower state of health status or
      well-being. These findings lead to the conclusion that being a veteran in the US
      does make a difference in regard to moving into various states of health status
      or well-being. This difference is supported by the estimated coefficient for
      veteran status being significant at a p value of 0.01 and through an evaluation
      of the estimated transition likelihood, controlling for veteran status. Veterans
      are less likely to die than their non-veteran counterparts, but have a greater
      likelihood of transition into levels of ADL dependence. Similarly, given the
      existence of a prior ADL limitation, over time, veterans are less likely to die,
      but more likely to move into a state of increased ADL limitations.

PMID- 9231947
TI  - A multicentre, double-blind, randomized study to compare the safety and efficacy
      of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein
      thrombosis in patients with acute ischaemic stroke.
AB  - A multicentre, double-blind, randomized study was performed in 179 patients with
      acute ischaemic stroke resulting in limb paresis. The purpose was to compare the
      safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin
      sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT).
      Prophylaxis started within 72 hours of the onset of stroke and continued for at
      least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg
      scanning which, if found positive, was followed by venography. A first computed
      tomography scan of the brain was performed at screening to rule out cerebral
      haemorrhage and a second at cessation of treatment to detect any haemorrhagic
      transformations. At the 2-3-months' follow-up period the patients were examined
      for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat
      analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of
      those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary
      embolism was diagnosed in one patient in each group. Major conversion to a
      symptomatic haemorrhagic brain infarct was found in one patient in each group.
      Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of
      patients treated with heparin (p = 0.135, NS). Deaths were mainly related to
      pulmonary infection and cerebral oedema, thus considered to be due directly to
      the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily
      is both safe and as effective as 5000 IU of heparin sodium twice daily given for
      DVT prophylaxis in patients with acute ischaemic stroke of recent onset.

PMID- 9231949
TI  - Bradyphrenia and parkinsonism.

PMID- 9231948
TI  - Neuropsychological test performance as an indicator of silent cerebrovascular
      disease in elderly hypertensives.

PMID- 9231950
TI  - The alerting effects of short and long naps in narcoleptic, sleep deprived, and
      alert individuals.
AB  - Eleven narcoleptic patients and 22 age- and gender-matched normal controls
      participated in a study to determine the alerting effects of differing nap
      lengths. All narcoleptic patients had been previously diagnosed [mean sleep
      latency on the multiple sleep latency test (MSLT) < or = 5 minutes with two or
      more sleep-onset rapid eye movement periods (SOREMPs)]. Healthy, normal subjects
      with a mean sleep latency on the screening MSLT > or = 8 minutes were randomly
      assigned to one of two groups (i.e. sleep-deprived and alert). All subjects
      completed two experimental night and days with at least 5 days between sessions.
      On the evening prior to each experimental day, narcoleptic and alert subjects
      spent 8 hours in bed and sleep-deprived subjects spent 0 hours in bed. The
      following day, all subjects underwent one of two napping conditions, 15 or 120
      minutes in bed. Both naps were terminated at noon. Every subject underwent both
      conditions and the order of conditions was counterbalanced. From 1215 to 1355
      hours all subjects underwent a modified MSLT. At 1500 hours, the subjects had a 1
      hour nap. The results showed that the 120-minute nap condition was more
      beneficial than the 15-minute nap. Narcoleptic and sleep deprived subjects were
      shown to have comparable levels of sleepiness on the modified MSLT. However, a
      differential response pattern on their latency to sleep was noted on the 1-hour
      nap. Sleep-deprived subjects were shown to be differentially more alert following
      a 120-minute nap opportunity. In contrast, for narcoleptic patients the
      beneficial effects of the nap were lost when tested 3 hours later. These results
      show that narcoleptic patients benefit from a longer nap but that these benefits
      are short-lived.

PMID- 9231951
TI  - The alpha attenuation test: assessing excessive daytime sleepiness in narcolepsy
      cataplexy.
AB  - Daytime sleep tendency was assessed in 10 drug-free patients with narcolepsy
      cataplexy and 10 normals matched for age and gender. Following nocturnal
      polysomnography, the alpha attenuation test (AAT) and the multiple sleep latency
      test (MSLT) were administered during five sessions occurring at 2-hour intervals
      beginning at 0900 and 1000 hours, respectively. For the AAT, participants were
      polysomnographically recorded for 8 minutes while seated in an illuminated room
      with their eyes alternately opened and closed. Power spectral analyses of
      electroencephalograph (EEG) activity at 02-A1 (10 second epochs) were calculated
      using fast Fourier transformations (FFT) within the alpha frequency range (8-12
      Hz) to obtain ratios of mean eyes-closed to mean eyes-open alpha power (i.e. the
      alpha attenuation coefficient, AAC). The narcoleptics were sleepier than the
      normals as indicated by a significantly smaller mean AAC and a significantly
      shorter mean latency to stage 1 on the MSLT. These findings suggest that the AAT
      may provide a quick and practical objective assessment of the excessive daytime
      sleepiness (EDS) associated with narcolepsy.

PMID- 9231952
TI  - Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance
      decrements during a week of sleep restricted to 4-5 hours per night.
AB  - To determine whether a cumulative sleep debt (in a range commonly experienced)
      would result in cumulative changes in measures of waking neurobehavioral
      alertness, 16 healthy young adults had their sleep restricted 33% below habitual
      sleep duration, to an average 4.98 hours per night [standard deviation (SD) =
      0.57] for seven consecutive nights. Subjects slept in the laboratory, and sleep
      and waking were monitored by staff and actigraphy. Three times each day (1000,
      1600, and 2200 hours) subjects were assessed for subjective sleepiness (SSS) and
      mood (POMS) and were evaluated on a brief performance battery that included
      psychomotor vigilance (PVT), probed memory (PRM), and serial-addition testing,
      Once each day they completed a series of visual analog scales (VAS) and reported
      sleepiness and somatic and cognitive/emotional problems. Sleep restriction
      resulted in statistically robust cumulative effects on waking functions. SSS
      ratings, subscale scores for fatigue, confusion, tension, and total mood
      disturbance from the POMS and VAS ratings of mental exhaustion and stress were
      evaluated across days of restricted sleep (p = 0.009 to p = 0.0001). PVT
      performance parameters, including the frequency and duration of lapses, were also
      significantly increased by restriction (p = 0.018 to p = 0.0001). Significant
      time-of-day effects were evident in SSS and PVT data, but time-of-day did not
      interact with the effects of sleep restriction across days. The temporal profiles
      of cumulative changes in neurobehavioral measures of alertness as a function of
      sleep restriction were generally consistent. Subjective changes tended to precede
      performance changes by 1 day, but overall changes in both classes of measure were
      greatest during the first 2 days (P1, P2) and last 2 days (P6, P7) of sleep
      restriction. Data from subsets of subjects also showed: 1) that significant
      decreases in the MSLT occurred during sleep restriction, 2) that the elevated
      sleepiness and performance deficits continued beyond day 7 of restriction, and 3)
      that recovery from these deficits appeared to require two full nights of sleep.
      The cumulative increase in performance lapses across days of sleep restriction
      correlated closely with MSLT results (r = -0.95) from an earlier comparable
      experiment by Carskadon and Dement (1). These findings suggest that cumulative
      nocturnal sleep debt had a dynamic and escalating analog in cumulative daytime
      sleepiness and that asymptotic or steady-state sleepiness was not achieved in
      response to sleep restriction.

PMID- 9231953
TI  - Night-to-night variability in CPAP use over the first three months of treatment.
AB  - The purpose of this study was to examine the relationship between night-to-night
      variability and nightly duration of continuous positive airway pressure (CPAP)
      therapy over the first 9 weeks of treatment and to determine when patients begin
      to establish a nonadherent pattern of use. Data were analyzed from a study of
      daily CPAP use covertly monitored in 32 diagnosed patients with obstructive sleep
      apnea (OSA) using a microprocessor monitor encased in a CPAP machine. Patterns of
      CPAP use were bimodal, based on the frequency of nightly use. Approximately half
      the subjects were consistent users of CPAP, applying it > 90% of the nights for
      an average of 6.22 +/- 1.21 hours per night, while the other half comprised
      intermittent users who had a wide range of daily use averaging 3.45 +/- 1.94
      hours per night on the nights CPAP was used. The percent of days skipped was
      significantly correlated with decreased nightly duration (rho = -0.73, p <
      0.0001). Analysis of the night-to-night pattern of use revealed that the two
      groups differed significantly in the nightly duration of CPAP use by the fourth
      day of treatment (p = 0.001). Exploration of factors that potentially
      differentiate the two groups revealed no reliable predictors. However,
      intermittent users continued to report significantly greater OSA symptoms
      (snoring, snorting, and apnea) posttreatment, suggesting that they continued to
      experience sleep disordered breathing.

PMID- 9231954
TI  - Compliance with nasal CPAP can be improved by simple interventions.
AB  - Effectiveness of continuous positive airway pressure (CPAP) as a treatment of
      obstructive sleep apnea can be limited by poor compliance, but little is known
      about how to improve compliance. We performed a randomized, controlled clinical
      trial among 33 subjects of two interventions to improve compliance. One group of
      subjects received weekly phone calls to uncover any problems and encourage use,
      another received written information about sleep apnea and the importance of
      regular CPAP use, and a third served as control subjects. We found that
      intervention improved CPAP compliance (p = 0.059) and that the effect was
      particularly strong when intervention occurred during the first month of CPAP
      treatment (p = 0.004). Although the sample size did not allow definitive
      investigation of other explanatory variables, subjects with lower levels of
      education or those with relatives who used CPAP may have benefited from
      intervention more than other subjects. We conclude that simple, inexpensive
      efforts to improve compliance with CPAP can be effective, especially when applied
      at the start of CPAP treatment, but optimal intervention may vary with certain
      patient characteristics.

PMID- 9231955
TI  - Cigarette smoking as a risk factor or an exacerbating factor for restless legs
      syndrome and sleep bruxism.
AB  - Cigarette smoking has been associated with sleep disturbances. However, little is
      known about how smoking affects restless legs syndrome (RLS) and sleep bruxism,
      two movement disorders associated with sleep. From a nationwide survey of 2,019
      Canadian adults, we estimated the prevalence of smoking to be 36%. Although there
      was no difference between smokers and nonsmokers for RLS prevalence, almost twice
      as many smokers (12%) as nonsmokers (7%) were aware of experiencing sleep
      bruxism. The estimated risk of a smoker suffering from RLS was nonsignificant. On
      the other hand, the risk of a smoker grinding his or her teeth was moderate (odds
      ratio = 1.9). Analysis of sleep laboratory findings revealed no differences in
      motor RLS and periodic leg movements in sleep (PLMS) indices between smoking and
      nonsmoking patients; after adjustment for age, there were no differences in sleep
      efficiency, latency, number of awakenings, or the arousal index for the RLS/PLMS
      patients. Among those suffering from bruxism, smokers had more tooth-grinding
      episodes than did nonsmokers (35.0 vs. 7.0; p = 0.056); none of the sleep
      variables differentiated sleep bruxism smokers from nonsmokers. It appears that
      cigarette smoking does not influence RLS/PLMS, whereas the risk that smoking and
      tooth grinding are concomitant is moderate. Smoking was not significantly
      associated with more motor activity in RLS/PLMS, but more grinding was noted in
      sleep bruxism.

PMID- 9231956
TI  - Circadian characteristics of sleep propensity function in healthy elderly: a
      comparison with young adults.
AB  - Changes in sleep-wake patterns are among the hallmarks of biological aging,
      Elderly persons complain of daytime drowsiness and difficulties in initiating and
      maintaining sleep. The question of whether age-related changes in sleep-wake
      distribution are the result of a dimunition in amplitude of the endogenous
      circadian pacemaker, resulting in a decline in nocturnal sleep tendency and an
      increase in diurnal sleep tendency, or a manifestation of the impact of the
      medical and psychosocial burden on sleep has not yet been fully determined. In
      the present study, we utilized a 7/13 ultrashort sleep-wake paradigm to
      investigate the 24-hour sleep propensity function (SPF) in healthy elderly
      persons. Seventeen healthy, elderly males, aged 65-78 years, and eight young
      males, aged 19-26, participated in the study. All elderly subjects were living
      independently in the community and were vigorous, physically active, and socially
      engaged. The young adult subjects were students living on campus, all with the
      same daily schedule. As anticipated, polysomnographic measures from the night
      prior to experimental periods differed between the elderly and young subjects.
      Specifically, the elderly had a reduction in percentage of sleep stage 3/4 and in
      sleep efficiency. The results of the 7/13 ultrashort sleep-wake paradigm showed
      that although aging did not affect the overall structure of the SPF, there was an
      age-related trend toward lower circadian amplitude and advanced phase. Our
      findings suggest that these age-related changes in sleep propensity may
      contribute to the difficulties in initiating sleep and to the early morning
      awakening.

PMID- 9231957
TI  - A finger-tapping task and a reaction time task as behavioral measures of the
      transition from wakefulness to sleep: which task interferes less with the sleep
      onset process.
AB  - The aim of this study was to assess whether a finger-tapping task (FTT), in which
      normal subjects repeatedly tap on a button while falling asleep, could be less
      disturbing and provide comparable information on the sleep onset period (SOP)
      with respect to a reaction-time task (RTT) to acoustic stimuli, in which the
      onset of sleep can be delayed by the arousing effect of the acoustic stimuli.
      Twelve subjects slept at their homes and six slept in a sleep laboratory for four
      consecutive nights. After one adaptation night and one baseline night, subjects
      were required to fall asleep in the third and fourth nights, bimanually
      performing either a RTT or a FTT. The results indicate that the FTT interfaces
      less with the SOP compared to the RTT and suggest that the FTT provides further
      advantages as a behavioral measure of the transition from wakefulness to sleep.
      In fact, the tapping task is associated with significantly shorter behavioral and
      polysomnographic sleep onset latencies and with a greater proportion of slow-wave
      sleep (SWS) during the transition from wakefulness to sleep compared with the
      RTT. Furthermore, correlations among subjective, behavioral, and
      electroencephalograph (EEG) latencies confirm the validity of the finger-tapping
      task as a behavioral measure of sleep onset.

PMID- 9231958
TI  - Distribution of delta activity across nonrapid eye movement sleep episodes in
      healthy young men.
AB  - The distribution of delta activity across successive nonrapid eye movement (NREM)
      sleep episodes and its night-to-night stability across three consecutive nights
      were investigated by studying delta power with spectral analysis in 31 healthy
      young men. Repeated-measures analysis of variance (ANOVA) with polynomial
      contrast was applied to grouped data of absolute delta power and three indexes:
      (1) the rate of delta power per NREM episode to its duration, 2) the standardized
      rate for the last NREM episode, and 3) the logarithm of the standardized rate. A
      significant linear decrease across NREM episodes was observed for each variable
      in each successive night. In addition, using night as a second within-subjects
      factor, no night effect was observed. Yet, the subsequent analysis of the
      logarithmic data yielded greater F values in all three nights' data as well as a
      linear function that accounted for a greater proportion of total variance than
      the analysis of the nonlogarithmic data. Since a linear decline for the logarithm
      of a variable implies an exponential distribution for that variable, we conclude
      that delta activity is distributed exponentially across NREM episodes, and this
      finding shows a remarkable night-to-night stability.

PMID- 9231959
TI  - Neovascularization induced by anulus and its inhibition by cartilage endplate.
      Its role in disc absorption.
AB  - STUDY DESIGN: A study of neovascularization with respect to the anulus and the
      endplate. OBJECTIVES: To determine the ability of the anulus and the endplate to
      induce neovascularization and to study the effect of the endplate on the
      neovascularizing activity of the anulus. SUMMARY OF BACKGROUND DATA: Previous
      studies showed that herniations contain varying amounts of nucleus pulposus,
      anulus fibrosus, and endplate. Results of recent studies have shown preferential
      neovascularization around the herniated anulus rather than the endplate. METHODS:
      Human L4-L5 discs were harvested from three specimens. In the left cornea of New
      Zealand White rabbits, an anulus (AF group) or an endplate (EP group) was
      implanted 4 mm from the superior corneoscleral limbus. In a third group (AF and
      EP group), an endplate was implanted between the anulus and the limbus. Twelve
      assays were done for each group. Sham surgeries were done on a fourth group as a
      control. Neovascularization was monitored by stereomicroscopy and scored from 0
      (no neovascularization) to +5 (capillaries growing around the implant).
      Histologic studies were done at weekly intervals. RESULTS: In the AF group, the
      anulus induced neovascularization in 11 or 12 corneas. By the third week, the
      anulus appeared thinner, and the newly formed vessels regressed. In the EP group,
      only two corneas showed neovascularization; 10 corneas showed no vascularization.
      In the AF and EP group, three corneas showed no neovascularization, seven had
      sustained neovascularization, and two had vascularization. In the corneas
      containing the endplates, the implants remained unchanged. Control corneas did
      show vascularization. Histologic sections showed that neovascularization and cell
      infiltration were most abundant in the AF group, followed by the AF&EP and the EP
      groups. CONCLUSION: The reactions to anulus fibrosus and to cartilage endplate
      differ. Anulus fibrosus may contain soluble substances that induce
      neovascularization, leading to its degradation and absorption. Cartilage endplate
      fails to induce neovascularization or diminishes the neovascular response,
      preventing its degradation. Disc herniations that contain a significant amount of
      endplate may not be degraded nor absorbed, leading to failure in spontaneous
      remission of symptoms.

PMID- 9231960
TI  - Treatment of canine intervertebral disc displacement with chondroitinase ABC.
AB  - STUDY DESIGN: This study demonstrated the therapeutic value of chemonucleolysis
      with chondroitinase ABC to canine intervertebral disc displacement. OBJECTIVES:
      To determine the efficacy of Chondroitinase ABC in the management of canine
      intervertebral disc displacement. SUMMARY OF BACKGROUND DATA: No previous study
      has assessed the chemonucleolysis with chondroitinase ABC in the displaced discs.
      The changes of intervertebral disc syndrome were evaluated in this study.
      METHODS: Fifty-nine dogs with symptoms and signs of intervertebral disc
      displacement were treated with Chondroitinase ABC by a single intradisc
      injection. The changes in symptoms and signs of disc herniation in the dogs were
      followed from 7 days to 3 years after treatment. RESULTS: Forty-eight dogs were
      evaluated for the efficacy of the chemonucleolytic treatment with chondroitinase
      ABC. At 1 week after injection, 45 of 48 dogs showed some improvement in symptoms
      and signs. No adverse reactions were observed. There was no recurrence of
      symptoms in nine dogs who were observed from 14 months to 3 years after
      injection. CONCLUSION: Chemonucleolytic treatment with chondroitinase ABC is an
      effective and safe method for the management of canine intervertebral disc
      displacement.

PMID- 9231961
TI  - Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by
      a resorbable gel (ADCON-L).
AB  - STUDY DESIGN: A canine lumbar laminotomy and discectomy model was used to
      evaluate the effects of a resorbable gel, ADCON-L (Gliatech Inc., Cleveland, OH),
      in reducing peridural scar formation and to assess the healing progress of
      immediately adjacent normal structures. OBJECTIVES: To compare peridural scar
      formation and anulus fibrosis healing with and without the use of ADCON-L in an
      animal model that closely replicates the common human surgical procedure. SUMMARY
      OF BACKGROUND DATA: ADCON-L has been shown to reduce the development of peridural
      scars in rat, rabbit, and canine laminectomy models in previous investigations;
      discectomies were not performed in these previous studies, however, and thus
      anular healing could not be assessed. METHODS: Seven adult mongrel dogs underwent
      a three-level unilateral lumbar hemilaminotomy and anular fenestration. In each
      dog, the ADCON-L was applied to two randomly assigned sites around the
      discectomy, the nerve roots, and the hemilaminotomy. The third site underwent
      surgery, but was left untreated (sham surgery only). The canines were killed 8
      weeks after surgery, and a gross anatomic assessment of scar formation was done
      using microdissection by an observer blinded to treatment. A numerical rating
      system was developed to assess the relative amount and tenacity of the anterior
      scarring (discectomy site) and posterior scarring (hemilaminotomy site). The
      healing of the anular defect was assessed histologically. RESULTS: ADCON-L
      significantly reduced peridural fibrosis in this lumbar discectomy model compared
      with the sham treated sites (p < 0.05). Further, the superficial layers, the
      posterior longitudinal ligament, and the anulus fibrosus healed well in the ADCON
      L treated sites. CONCLUSIONS: ADCON-L reduced local peridural fibrosis after
      lumbar laminotomy and discectomy without impacting the healing of the surrounding
      tissues.

PMID- 9231962
TI  - An experimental study of lumbar destabilization. Restabilization and bone
      density.
AB  - STUDY DESIGN: An investigation of the effects of bone density on lumbar spine
      stability using destabilizing and restabilizing procedures. OBJECTIVES: To
      measure cadaveric vertebral bone densities computed tomographic scans and to
      correlate the measured densities with lumbar spine stability in the intact and
      during sequential destabilization and restabilization. SUMMARY OF BACKGROUND
      DATA: The stabilizing effects of lumbar pedicle screw fixation have been widely
      described. Numerous construct failure mechanisms have been observed, including
      screw loosening in osteoporosis. Although previous studies have analyzed the
      effect of bone density on the compression strength of bone similar to that used
      in interbody fusion and the relationship of pedicle screw pull-out strength to
      vertebral bone density, a combined study of bone density and construct stability
      using an interbody bone spacer with pedicle fixation has not been performed.
      METHODS: Bone densities were measured in 20 human cadaveric lumbar spines using
      computed tomography scans and a hydroxyapatite phantom. After the specimens were
      mounted in a testing frame, the L4-L5 motion segments were subjected to cyclic
      axial compression-torsional loads, and axial and rotational intervertebral
      displacements were monitored. Laminectomy, facetectomy, and pedicle screw-plate
      fixation were performed sequentially in three specimens. Ten others underwent
      these procedures with an additional destabilization procedure, discectomy, after
      facetectomy. Seven others underwent the same sequence as the previous group,
      followed by the insertion of interbody bone. Cyclic testing was resumed after
      each procedure. RESULTS: Average bone densities varied widely among the
      specimens. Average bone densities of the pedicle and of the vertebral body for
      individual specimens were well-correlated (r = 0.897). Displacements were
      recorded as a percentage of the intact state before destabilization; average
      percentages are reported as follows: axial displacements increased after
      facetectomy (145%) and subsequent discectomy (251%), and rotational displacements
      increased after facetectomy (295%) and discectomy (390%). Instrumentation without
      interbody bone resulted in specimens with decreased axial (126%) and rotational
      (156%) displacements. The addition of interbody bone further decreased axial
      (111%) and rotational (117%) displacements. The rotational stabilization provided
      by instrumentation was well-correlated with vertebral bone density (r = 0.804).
      This correlation was enhanced by the use of interbody bone (r = 0.939).
      CONCLUSION: The unstable lumbar spine can be partially stabilized using fixation.
      Interbody bone provides additional stability. The immediate stability provided by
      pedicle screws is greater in lumbar vertebrae with higher bone density.

PMID- 9231963
TI  - The effect of bone quality on pedicle screw loading in axial instability. A
      synthetic model.
AB  - STUDY DESIGN: In this biomechanical analysis of pedicle screw bending moments,
      custom-fabricated vertebral analogues were loaded in axial compression to produce
      sagittal bending forces. Moments were measured directly from internally
      instrumented pedicle screws. OBJECTIVES: To establish the role of cancellous
      vertebral modulus on pedicle screw bending moments within the vertebral body and
      the vertebral pedicle. SUMMARY OF BACKGROUND DATA: Pedicle screws are often used
      to manage axial instability of the spine. Clinical studies report a high
      incidence of screw bending failure, resulting in kyphosis and pain in some
      patients. Factors predisposing to bending failure are not well understood,
      although recent studies have shown that vertebral morphometry is important.
      METHODS: Axially canullated 7.0-mm pedicle screws, internally instrumented with
      paired strain gauges, were inserted into analogue vertebrae of uniform dimension.
      Cancellous modulus was varied from 25-100 MPa. Screws were rigidly mounted to a
      vertical testing frame, and axial loads were applied to the superior vertebral
      endplate, producing sagittal bending moments. Moments were recorded from gauges
      applied in the intrapedicular and intravertebral portions of the screw. Mean
      moments were compared using a Student's t test, with significance defined as P <
      0.05. RESULTS: Cancellous modulus did not affect bending moments experienced in
      either the intrapedicular or intravertebral portions of the pedicle screws. Gauge
      accuracy was excellent, and with no gauge drift. CONCLUSIONS: Although small
      changes in pedicle morphometry can alter screw bending moments significantly,
      changes in cancellous modulus had no measurable impact on bending moments at
      these same loads. Bone density is likely to play a limited role in screw bending
      failure.

PMID- 9231964
TI  - Natural history of scoliosis in the institutionalized adult cerebral palsy
      population.
AB  - STUDY DESIGN: Fifty-six residents with cerebral palsy and significant scoliosis
      or kyphosis at the Hazelwood Center in Louisville, Kentucky were studied
      periodically using radiographs to assess the degree of scoliosis, kyphosis, and
      pelvic obliquity and by clinical evaluation to assess functional status and skin
      condition. OBJECTIVES: This study followed the natural history of untreated
      scoliosis to determine whether a decline in functional status is related to curve
      progression and whether the development of decubiti is associated with the degree
      of pelvic obliquity. Identifying the factors that affect functional decline may
      help develop treatment plans to minimize it. SUMMARY OF BACKGROUND DATA:
      Significant structural deformities of the spine often accompany cerebral palsy.
      Despite the relatively large number of cases, little is known about the natural
      history of untreated scoliosis in the adult cerebral palsy population.
      Theoretically, curve progression will lead to pain, loss of ambulation or sitting
      balance, or even cardiopulmonary compromise, but few studies have been done to
      verify this. METHODS: Single-factor analysis of variance was used to compare the
      curve progression rate within groups based on the structure of the curve, and the
      two-sample student t test was used to compare the average initial curve, the
      average final curve, the progression rate, and the amount of progression between
      groups based on functional decline. The two sample t test also was used to
      correlate the average pelvic obliquity and the size of the final curve with the
      presence or absence of decubiti. RESULTS: Functionally, 10 patients (18%)
      declined during the course of the study. In these 10 patients, the average
      initial curve was 41.1 degrees, the average final curve was 80.6 degrees, and the
      average progression rate was 4.4 degrees per year. For the stable patients, the
      average initial curve was 33.9 degrees, the average final curve was 56.5 degrees,
      and the average progression rate was 3.0 degrees per year. The differences
      between the final curve and the absolute amount of progression were statistically
      significant (P = 0.018 and P = 0.03, respectively). Three patients developed
      decubiti. Their curve averaged 106 degrees, and their pelvic obliquity measured
      45 degrees, both of which were significantly higher than those of the patients
      without decubiti. CONCLUSIONS: The results of the present study demonstrate that
      in the adult patient with cerebral palsy and scoliosis, a definite correlation
      exists between deformity size and functional decline and decubiti. Progression
      rate also seems to be a factor in functional decline. Additional studies are
      needed to determine whether surgical intervention will halt or reverse the
      decline.

PMID- 9231965
TI  - Freeze-dried allograft for posterior spinal fusion in patients with neuromuscular
      spinal deformities.
AB  - STUDY DESIGN: The effectiveness and safety of freeze-dried allograft for
      posterior spinal fusion in patients with neuromuscular disorders were evaluated
      retrospectively. SUMMARY OF BACKGROUND DATA: Because the harvest of an adequate
      quantity of autogenous bone graft from patients with neuromuscular deformity who
      have instrumentation and fusion to the pelvis is difficult at best, an
      alternative graft source usually is needed. Allograft bone, most commonly
      processed fresh-frozen or freeze-dried, has been used frequently for posterior
      spinal fusion in patients with neuromuscular deformity. However, a relatively
      high risk of infection and pseudarthrosis has been reported for this procedure.
      METHODS: Forty patients with neuromuscular deformity with an average age at the
      time of surgery of 14 years and 2 months (range, 5 years, 4 months to 23 years, 8
      months) met the inclusion criteria. All of these patients underwent more than 2
      years of follow-up evaluation. They were evaluated for rates of infection,
      pseudarthrosis, and transmissible disease. RESULTS: Thirty-eight patients had
      solid fusion at the most recent follow-up visit. Definite pseudarthrosis was
      detected in one patient (2.5% of the study group), which was treated
      successfully. Another patient's (2.5%) spinal curve progression of more that 10
      degrees and rod breakage led the authors to diagnoses a probable pseudarthrosis.
      She had a stable spine that did not require revision at 68 months after surgery.
      For the 32 patients who underwent posterior surgery only, the pseudarthrosis rate
      was 3.1%. There were no acute deep wound infections. Superficial infection
      occurred in two patients (5%) and delayed deep sterile drainage in one patient
      (2.5%). All cases of infection resolved with appropriate management. Delayed deep
      wound infection developed in one patient (2.5%) as a result of staphylococcus
      coagulase negative at 34 months after surgery. Successful treatment has consisted
      of implant removal, debridement, and appropriate antibiotics. Transmissible
      disease attributable to allograft has not been detected to date. CONCLUSION:
      Freeze-dried allograft fusion is a reliable and effective method for posterior
      spinal fusion in the patients with neuromuscular deformity.

PMID- 9231966
TI  - Radiographic standing cervical segmental alignment in adult volunteers without
      neck symptoms.
AB  - STUDY DESIGN: A radiographic evaluation of standing cervical and global sagittal
      alignment in 100 adult volunteers with no neck or radicular arm symptoms was
      undertaken. OBJECTIVES: To document and define cervical standing lateral
      alignment and balance in a volunteer population without cervical problems.
      SUMMARY OF BACKGROUND DATA: Minimal data exist on cervical segmental sagittal
      alignment distributions in stance. METHODS: Radiographic measures of spinal
      alignment were collected and statistically analyzed. RESULTS: Data were
      categorized into two age- and sex-matched groups. Group 1 had no cervical or
      lumbar symptoms. Group 2 had no cervical symptoms, but had lumbar symptoms. Mean
      total and segmental cervical alignment distributions were not statistically
      different between groups. Mean total cervical lordosis in stance for the entire
      group was -40.0 +/- 9.7 degrees. Thoracic and lumbar alignment were within
      previously reported measures and not statistically different between groups.
      Plumb line markers at C7 and sacral reference points were not statistically
      different between groups. Pearson correlations revealed that cervical sagittal
      plane alignment vaired inversely with thoracic alignment. Independent
      orthopedists noted cervical osteoarthritis was present in 17% of each group of
      volunteers with substantial kappa agreement (0.73) between observers.
      Intraobserver and interobserver reliability of sagittal alignment measures of 30
      randomly remeasured radiographs revealed strong correlation between observations.
      CONCLUSIONS: No differences in total cervical lordosis were noted between
      cervical asymptomatic volunteers with or without low back pain. Most cervical
      lordosis occurred at the C1-C2 level in stance, whereas only 6 degrees (15%)
      occurred at the lowest three cervical levels (C4-C7). Changes in cervical
      lordosis correlated inversely with changes in thoracic alignment.

PMID- 9231967
TI  - Disorders of the back and spine in construction workers. Prevalence and
      prognostic value for disability.
AB  - STUDY DESIGN: A cohort study on back-related morbidity and its impact on early
      retirement resulting from disability among employees in the construction
      industry. OBJECTIVE: To describe the prevalence of back-related morbidity
      according to different measures in various occupational groups and to assess the
      prognostic value of these measures for early retirement resulting from
      disability. METHODS: The results of occupational health examinations conducted in
      1986-1988 among 4,958 employees of the German construction industry aged 40-64
      years were analyzed. Active follow-up evaluation was carried out between October
      1992 and July 1994 to ascertain employment status. RESULTS: Compared with that of
      white-collar employees, no excess risk for self-reported back pain or sciatica
      was seen for any of the manual professions. In contrast, the age-adjusted
      prevalence of clinical findings of the spine was elevated among all employees in
      manual professions, and the prevalence of a recorded diagnosis related to
      disorders of the back and spine (ICD-9 position 720-724) was elevated among
      bricklayers compared with white-collar employees. The relative risk of being
      granted a disability pension in the follow-up period was 1.6 (95% Confidence
      Interval [Cl], 1.3-2.1) for persons reporting back pain or sciatica, 1.8 (95% Cl,
      1.4-2.2) for persons with an abnormal clinical finding of the spine, and 1.5 (95%
      Cl, 1.2-1.8) for persons with a recorded medical diagnosis related to disorders
      of the back or spine (ICD-9 720-724). CONCLUSION: Patterns of morbidity varied
      according to the evaluated morbidity measure. All three measures qualified as
      significant predictors of disability and helped to identify high-risk occupations
      and high-risk employees.

PMID- 9231968
TI  - A familial predisposition toward lumbar disc injury.
AB  - STUDY DESIGN: A retrospective case-control study was performed. OBJECTIVES: To
      test the hypothesis that there is a familial predisposition to lumbar disc pain
      and injury. SUMMARY OF BACKGROUND DATA: The few studies that have addressed this
      question have suggested that a familial predisposition is present, but the
      techniques used for identifying discogenic pain and accounting for potentially
      confounding extrinsic factors make it difficult to formulate a clear conclusion.
      METHODS: Immediate relatives of index patients who had surgically proven lumbar
      disc herniations (disc/case subjects) or repetitive upper extremity overuse
      syndromes (upper extremity/control subjects) were given a questionnaire that had
      been tested previously and found to reliably identify discogenic lower back pain.
      The prevalence of lumbar disc pain and injury was determined in the two groups of
      patients; logistic regression was used to control for demographic factors and
      activities known to increase risk for lumbar disc injury. RESULTS: The
      questionnaire was returned by 60 (59%) of 102 disc subjects and 41 (50%) of 81
      upper extremity subjects. Sixteen (28%) disc subjects and one (2%) of the upper
      extremity subjects met questionnaire criteria for discogenic lumbar pain; seven
      (12%) disc subjects and no upper extremity subjects had received surgical therapy
      for lumbar disc pain. Logistic regression analysis identified familial grouping
      and a history of lifting as the only variables associated with a positive
      response on the questionnaire. Information obtained from index patients about
      their nonresponding relatives' history of significant back pain suggested similar
      findings. CONCLUSIONS: There is a familial predisposition toward lumbar disc pain
      and injury. This information may be helpful in occupational counseling or for
      targeting specific populations with preventative, interventional strategies.

PMID- 9231969
TI  - The effect of dynamic strength back exercise and/or a home training program in 57
      year-old women with chronic low back pain. Results of a prospective randomized
      study with a 3-year follow-up period.
AB  - STUDY DESIGN: A prospective, randomized investigation. OBJECTIVES: To compare the
      effect of dynamic strength back muscle training with that of a home training
      program and to evaluate the long-term effect of the home training program in
      patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: In a health
      survey of 57-year-old women, those with chronic low back pain were selected using
      the Nordic Questionnaire. Of 172 women with low back pain, 74 participated in the
      study. METHODS: The participants were randomly assigned to either dynamic
      strength back exercises at a fitness center and a home training program or to the
      home training program for the first 3 months, after which both groups continued
      to pursue the home training program. Follow-up observation was by examination at
      3 and 12 months and by mailed questionnaire after 3 years. The primary effect
      variables were disability, sick-leave, and use of health care services. RESULTS:
      Both training groups manifested significant improvement at the 3- and 12-month
      follow-up examinations, yet the adherence rate was much better in the group
      assigned to the fitness center. Those who adhered to the training program for the
      first year manifested significant improvement according to the 3-year follow-up
      questionnaire. There was a significant reduction in the number of women on sick
      leave and in use of health care services after 1 year, but not after 3 years.
      CONCLUSIONS: The home training program was as effective as the supervised dynamic
      strength muscle training program and yielded lasting improvement after at least 1
      year of adherence. The adherence rate was much better, however, when the training
      was supervised at the start.

PMID- 9231970
TI  - Relationship between subjective neck disorders and cervical spine mobility and
      motion-related pain in male machine operators.
AB  - STUDY DESIGN: In a single blinded procedure, quantified cervical clinical tests
      were performed on machine operators with and without subjective reports of neck
      pain. OBJECTIVES: To evaluate whether subjective reports of neck pain are
      associated with limited and painful cervical spine mobility. SUMMARY OF
      BACKGROUND DATA: Spinal motion evaluation and pain rating are commonly used for
      assessing impairment in patients with spinal disorders. However, it is still
      unclear how cervical spinal motion and corresponding pain rating are affected by
      subjective reports of neck pain. METHODS: Forty-nine male forest machine
      operators completed the Standardized Nordic questionnaire on musculoskeletal
      symptoms. Maximal voluntary cervical spinal flexion-extension, bilateral axial
      rotation, and lateral flexion were measured with a goniometer ad modum Myrin,
      while corresponding pain was rated on Borg's scale. RESULTS: Nineteen men (38.8%)
      reported no neck pain within the past 12 months, nine men (18.4%) reported pain
      during the past 12 months (but not during the past 7 days), and 21 men (42.8%)
      had experienced neck pain during the past 7 days. The results of two of the range
      of-motion tests (flexion and left axial rotation) and three of the pain ratings
      (during flexion, extension, and left axial rotation) differed significantly
      between men who reported pain the past 7 days and those with no pain, and they
      correlated significantly with the severity of pain as reported in the
      questionnaire. CONCLUSIONS: Many forest machine operators reporting neck pain in
      the Nordic questionnaire did have limited and painful cervical spine mobility.
      Range-of-motion tests may be useful tools to describe impairment and constitute a
      basis for assessment for therapeutic interventions.

PMID- 9231971
TI  - Lumbar-hip flexion motion. A comparative study between asymptomatic and chronic
      low back pain in 18- to 36-year-old men.
AB  - STUDY DESIGN: The amount of lumbar and hip flexion and the relative contribution
      within movement during standing forward bending was recorded on a group of
      asymptomatic men and a group of men with a history of chronic low back pain.
      OBJECTIVES: To compare the relative contribution of the hip and lumbar spine to
      forward bending in the two groups. SUMMARY OF BACKGROUND DATA: The hips and
      lumbar spine both contribute to the forward bending motion, and an aberrant
      pattern of contribution in one or both regions could be related to the presence
      of chronic low back pain. METHODS: Thirty-two white men aged 18-36 years (15 with
      chronic low back pain and 17 asymptomatic) were assessed using a three
      dimensional motion analysis system that allowed uninterrupted forward bending.
      RESULTS: The men with chronic low back pain demonstrated a significant reduction
      in the mean total range and mean maximum lumbar flexion relative to the
      asymptomatic group. Mean hip flexion was not significantly different. Data
      analysis for 120 degrees of gross flexion revealed a subgroup of men with chronic
      low back pain with a significant decrease in hip flexion. CONCLUSIONS: When
      assessing the relative motion of the lumbar spine and hips in standing forward
      flexion, there was measurable difference between asymptomatic men and a group of
      chronic low back pain patients. In particular, two subgroups of individuals with
      chronic low back pain appeared; one moved relatively similarly to the
      asymptomatic group, whereas the other sub-group demonstrated reduced hip
      mobility. These findings indicate the importance of assessing the lumbar and hip
      flexion motion in chronic low back pain patients to determine if a movement
      abnormality is present.

PMID- 9231973
TI  - Extension injury of the thoracolumbar spine.
AB  - STUDY DESIGN: This is a report of a patient with a rare fracture in the
      thoracolumbar spine. OBJECTIVES: To illustrate the previously undescribed
      fracture in the thoracolumbar spine and to propose a new mechanism of this rare
      lesion with a literature review. SUMMARY OF BACKGROUND DATA: Extension injury of
      the thoracolumbar spine is uncommon. Although there have been several reports of
      hyperextension injuries in the thoracolumbar spine, the injury mechanism of the
      present case was different from those in the previously reported cases. METHODS:
      The clinical findings, roentgenographic appearance, treatment, and follow-up
      result were presented, and the mechanism of this lesion was analyzed. RESULTS:
      Physical examination revealed no neurologic deficit. Radiographs showed the
      oblique fracture line extended from the middle region of the L1-L2 disc to the
      posteroinferior edge of the L2 vertebral body, with the widening of bilateral L2
      L3 facet joints. The patient was treated conservatively with a successful
      outcome. Two years after his injury, the patient had resumed his previous
      activity completely. CONCLUSIONS: The authors considered that the mechanism of
      this rare injury was a combination of hyperextension force and axial loading.

PMID- 9231972
TI  - The prognosis of low back pain in general practice.
AB  - STUDY DESIGN: A prospective cohort study on low back pain in consecutive patients
      in general practice, in which potential prognostic indicators at baseline and at
      the 1-year follow-up examination were assessed by means of four weekly
      questionnaires. OBJECTIVES: To identify prognostic indicators of the duration of
      low back pain in general practice and the occurrence of a relapse. BACKGROUND:
      Little is known about the prognosis of low back pain in general practice.
      Different designs and different results of preceding studies make drawing
      conclusions about the prognostic indicators, in any, of the course of low back
      pain in general practice difficult. METHODS: For a period of 2 years, 15 general
      practitioners from Amsterdam and surrounding areas studied consecutive patients
      with chronic low back pain and those with a recent onset of low back pain. A
      large number of potential prognostic indicators were assessed at the initial
      visit. After the initial visit, each patient was monitored for a period of 12
      months. The follow-up assessment was conducted with four weekly postal
      questionnaires. The associations among the potential prognostic indicators, the
      duration of the index episode, and the occurrence of a relapse were analyzed
      using multivariate Cox regression and logistic regression analysis, respectively.
      RESULTS: Of the 605 patients identified, 443 were included in the follow-up
      period of assessment; the questionnaires were completed by 269 patients. In
      general, patients with less severe low back pain participated less often or did
      not complete the follow-up study. Thirty-five percent of the population still
      experienced low back pain after 12 weeks, and 10% still experienced it after 1
      year. Approximately three of every four patients whose index episode ended before
      the end of the follow-up period had one or more relapses within a year. The
      analysis resulted in a model with four variables predicting the duration of the
      low back pain, including "the duration of the low back pain preceding the initial
      visit," "receiving physical therapy," "pain intensity", and "history of back
      surgery." Daily functioning appeared to be the only variable that was
      significantly associated with the occurrence of a relapse. CONCLUSIONS: Only a
      few variables appear to be related to the clinical course of low back pain seen
      in general practice. In particular, the duration preceding the initial visit and,
      unexpectedly, receiving physical therapy were both associated with a longer
      duration of low back pain.

PMID- 9231974
TI  - Neurologic safety in spinal deformity surgery.
AB  - Paralysis following surgery to correct spinal deformity can be a catastrophic
      problem. Surgeons must be aware that there are a multitude of risk factors
      related to the etiology and pattern of deformity and that there are a multitude
      of events and actions in the operating room and after the surgery that influence
      the development of paralysis. Patients and families need to know that although
      paralysis can occur, it is rare, and that it can occur despite the very best
      efforts of the surgeon. This is a review of the available literature on the
      subject and some personal experiences of the author.

PMID- 9231976
TI  - HIZ lesions.

PMID- 9231975
TI  - A system for reporting the size and location of lesions in the spine.
AB  - STUDY DESIGN: A description of a method for standardizing the nomenclature used
      in reporting the size and location of lesions in the lumbar or thoracic spine is
      presented. OBJECTIVES: To make the reporting of findings on computed tomography
      or magnetic resonance imaging scans simpler and more accurate. SUMMARY OF
      BACKGROUND DATA: Over the past 10 years, three other systems have been proposed,
      and parts of each have been incorporated in this system. METHODS: This is a
      multicenter report. A group of 12 prominent physicians, including radiologists,
      neurosurgeons, orthopedic surgeons, and physiatrists, at 11 centers collaborated
      in the formulation of this system. RESULTS: In this system, areas in the axial
      plane, i.e., medial to lateral, are called "zones," and in the caudocranial
      direction, they are called "levels." The zones are the central canal zone, the
      subarticular zone, the foraminal zone, and the extraforaminal zone. In the
      caudocranial direction, the levels from above downward are the suprapedicle
      level, the pedicle level, the infrapedicle level, and the disc level. The size of
      a lesion can be rated by the descriptive words normal, mild, moderate, moderately
      severe, and severe, or by the numbers 1 to 5, with the number 1 indicating normal
      and the number 5 indicating severe. CONCLUSIONS: The authors of the present study
      believe that all health care professionals who care for the spine will find this
      nomenclature valuable in communicating with each other, in writing medical
      reports, in presenting reports at meetings, or in writing scientific articles.

PMID- 9231977
TI  - Development of FIV-specific cytolytic T-lymphocyte responses in cats upon
      immunisation with FIV vaccines.
AB  - Vaccine protection has been achieved in cats against experimental infection with
      feline immunodeficiency virus (FIV). Such protection has been attributed to FIV
      specific humoral immunity, as well as cellular immunity of unknown mechanism(s).
      Since cell-mediated immunity plays a crucial role in the clearance of viral
      infections, this study evaluated the role of FIV-specific CTL in vaccine
      prophylaxis. Cats were immunised with inactivated FIV vaccines, reported to have
      > 90% vaccine efficacy. Significant levels of specific CTL activity were detected
      following the third immunisation. CTL activity persisted for several months and
      could be enhanced through a booster immunisation. The levels of CTL activity were
      comparable to those induced by a recombinant canarypoxvirus based FIV vaccine.
      These results suggest a possible role for CTL-mediated immunity in vaccine
      protection against FIV infection in cats.

PMID- 9231978
TI  - Effect of in vitro maedi-visna virus infection on adherence and phagocytosis of
      staphylococci by ovine cells.
AB  - This work was aimed at studying the effect of maedi-visna virus (MVV) infection
      in vitro on the ability of sheep cells to adhere to staphylococci (Staphylococcus
      aureus and Staphylococcus epidermidis), and phagocytose these bacteria. Adherence
      was studied in sheep choroid plexus cells (SCPC) using an ELISA test and
      phagocytosis was studied in pulmonary alveolar macrophages (PAM) by
      chemiluminescence. A 5- and 7-day of in vitro MVV infection resulted in syncytium
      formation and a significant increased adherence (P < 0.01) of SCPC to bacteria.
      SCPC endogenous fibronectin was significantly higher (P < 0.01) on days 5 and 7
      than on day 0 of MVV infection. A significantly decreased phagocytosis (P < 0.05)
      was also observed on days 5 and 7 of MVV infection in PAM when compared to MVV
      free controls. Comparatively, phagocytosis was highest for S. aureus non-slime
      producing strains, followed by S. epidermidis, and S. aureus slime producing
      strains, in that order. Finally, increased expression of both, class I and class
      II major histocompatibility antigens was also observed in MVV-infected PAM on
      days 5 and 7, whereas SCPC only demonstrated upregulation of MHC class I. These
      results, indicative of an alteration of some cell functions in MVV-infected
      cells, may help to understand interactions between MVV-infected cells and
      bacteria in simultaneous infections and may provide clues to the possible in vivo
      interactions of both pathogens.

PMID- 9231979
TI  - Turkey rhinotracheitis virus and Escherichia coli experimental infection in
      chickens: histopathological, immunocytochemical and microbiological study.
AB  - The aim of this study was to evaluate the response of chickens to a combined
      infection with turkey rhinotracheitis virus (TRTV) and Escherichia coli O78:K80.
      Groups of specific-pathogen-free chickens were inoculated by eyedrop and
      intranasal routes with TRTV and/or E. coli O78:K80. Presence of E. coli O78:K80,
      histopathological changes and tissue distribution of viral antigen in the
      respiratory tract of chickens were evaluated. Dual infection resulted in
      increased severity of clinical signs, and macroscopic and microscopic lesions
      compared with those groups given single infections. All 36 chickens inoculated
      with TRTV plus E. coli O78:K80 showed severe rhinitis. Moreover, periorbital
      edema and fibrinous airsacculitis and pericarditis were observed in one of the
      three chickens inoculated with both agents and sacrificed at day 5 p.i. In
      addition, purulent material in the air spaces of the cranial bones was seen in
      three of the six animals from the same group sacrificed at days 5 and 7 p.i. The
      distribution of viral antigen in tissues was similar in groups inoculated with
      TRTV and TRTV plus E. coli, but viral antigen was detected only in main bronchi
      of chickens from the latter group. The quantity of E. coli O78:K80 isolated from
      the nasal cavity was greater in the group given dual infection. The results
      obtained suggest that TRTV may act as primary agent, enhancing E. coli
      multiplication. The lesions observed in the group inoculated with both agents
      could correspond to an initial stage of swollen head syndrome (SHS) and
      contribute to the hypothesis that SHS could be due to a mixed infection with TRTV
      and E. coli.

PMID- 9231980
TI  - Sheep do not have a major role in bovine herpesvirus 1 transmission.
AB  - With regard to BHV1 eradication programs in cattle it is important to know
      whether sheep can be a reservoir of BHV1. We therefore performed an experiment
      that consisted of three phases. In phase 1, 10 sheep were inoculated with high
      doses of BHV1 and kept in close contact with 5 sheep and 5 calves. All inoculated
      sheep excreted BHV1 between 8 and 15 days post inoculation and seroconverted.
      Although BHV1 was isolated from the nasal mucosa of 3 out of 5 sentinel sheep,
      none of the sentinel sheep produced antibodies against BHV1. One sentinel calf
      excreted BHV1 through days 12-17; the remaining 4 calves excreted BHV1 between
      days 18 and 24 suggesting that the first calf was infected by sheep and the
      remaining 4 sentinel calves were infected by that calf and not by sheep. The
      bacic reproduction ratio (R0) of BHV1 between sheep and calves was estimated at
      0.1, and among calves it was estimated at > or = 9. In phase 2, all inoculated
      sheep were treated with dexamethasone and kept in close contact with 5 sheep and
      5 calves. All dexamethasone treated sheep re-excreted BHV1 over a 6- to 9-day
      period. None of the sentinel animals seroconverted. In phase 3, the sentinel
      sheep and calves of phase 1 were kept in two groups and were treated with
      dexamethasone. None of the sentinel sheep re-excreted BHV1, whereas 3 out of 5
      sentinel calves did. It is concluded that while BHV1 infection in sheep is
      possible, BHV1 does not spread from sheep easily to cattle.

PMID- 9231982
TI  - Porcine reproductive and respiratory syndrome virus: routes of excretion.
AB  - This study was conducted to delineate potential sites of exit and duration of
      shedding of porcine reproductive and respiratory syndrome virus (PRRSV). Two
      experiments of 6 pigs each were conducted. Pigs were farrowed in isolation,
      weaned at 7 days of age, and housed in individual HEPA filtered isolation
      chambers. In each experiment, 3 pigs served as controls and 3 were inoculated
      intranasally with PRRSV (ATCC VR-2402) at 3 weeks of age. In a first experiment,
      on days 7, 14, 21, 28, 35, and 42 post-inoculation (p.i.), pigs were anesthetized
      and intubated. The following samples were collected: serum, saliva, conjunctival
      swabs, urine by cystocentesis, and feces. Upon recovery from anesthesia, the
      endotracheal tube was removed, rinsed, and the rinse retained. In the second
      experiment, the sampling schedule was expanded and serum, saliva, and
      oropharyngeal samples were collected from day 55 to day 124 p.i. at 14 day
      intervals. Virus was isolated in porcine alveolar macrophages up to day 14 from
      urine, day 21 from serum, day 35 from endotracheal tube rinse, day 42 from
      saliva, and day 84 from oropharyngeal samples. No virus was recovered from
      conjunctival swabs, fecal samples, or negative control samples. This is the first
      report of isolation of PRRSV from saliva. Virus-contaminated saliva, especially
      when considered in the context of social dominance behavior among pigs, may plan
      an important role in PRRSV transmission. These results support previous reports
      of persistent infection with PRRSV with prolonged recovery of virus from tonsils
      of swine.

PMID- 9231981
TI  - Colorimetric detection of lagomorphs' calicivirus genomic sequences by polymerase
      chain reaction incorporating digoxigenin dUTP.
AB  - A method of reverse transcription followed by polymerase chain reaction (RT-PCR)
      has been implemented for the demonstration of the rabbit haemorrhagic disease
      virus (RHDV) genome in organ suspensions, leukocytes and excretions of infected
      rabbits. RT-PCR has been tested with 10 RHDV strains isolated at various
      geographic sites and times using a pair of primers coming from the gene region
      coding for the capsid protein VP60. The same primers were effective in the
      amplification of 4 of 5 European brown hare syndrome (EBHS) virus isolates. Non
      radioactive labelling of PCR products with digoxigenin during the amplification
      and a system of colorimetric assessment of hybridization reactions between a
      biotin-labelled RHDV capture probe and the chains of labelled amplicons (PCR
      ELISA) were used for specific analyses of nucleic acid synthesis. The sensitivity
      of the alternative procedure of analysis of the dig-labelled PCR products with
      PCR ELISA was two logs10 higher than that of conventional electrophoresis in
      agarose gel stained with ethidium bromide. The results of the hybridization
      reactions, carried out under various stringency conditions, have confirmed the
      presumption that the genomic similarity between the amplified and the probed
      areas of the capsid protein VP60 gene was not uniform within all the tested
      caliciviruses. A higher degree of heterogeneity was observed between the isolates
      of EBHSV and RHDV.

PMID- 9231983
TI  - Determinants of persistence in canine distemper viruses.
AB  - Viral persistence in the central nervous system is the driving force behind the
      chronic progressive disease caused by natural canine distemper virus (CDV)
      infection in dogs. Persistence of CDV is associated with non-cytolytic spread and
      impaired viral budding. Since budding is to a large extend dependent on the
      nucleocapsid-(N) and matrixproteins (M) of the virus, we analyzed the nucleotide-
      and deduced amino acid sequences of the corresponding genes of a spectrum of CDV
      strains, that differ with respect to virulence and persistence in vivo and in
      vitro. The wild type CDV (A75/17), which is capable of causing a persistent
      infection in vivo was compared to two tissue culture adapted CDV strains
      (passaged A75/17-CDV and Rockborn-CDV), which CDV strains, that differ with
      respect to virulence and persistence in vivo and in vitro. The wild type CDV
      (A75/17), which is capable of causing a persistent infection in vivo was compared
      to two tissue culture adapted CDV strains (passaged A75/17-CDV and Rockborn-CDV),
      which retain a residual virulence and the capacity to spontaneously persist in
      vitro. A modified distemper virus (Snyder Hill-CDV), which is neurovirulent but
      not capable of causing a persistent infection in vivo, and an avianized virus
      (Onderstepoort-CDV) which is completely apathogenic and spreads by budding in
      cell cultures were also examined. Differences were found in the C-terminal of the
      nucleocapsid protein, which--comparing the two extremes of the spectrum (wild
      A75/17-CDV and OP-CDV)--lead to changes of the predicted protein structure. Such
      changes could affect the budding process and thus play a role in persistence.
      Marked changes in the M-gene were found in its non-coding region: the nucleotide
      sequences of the SH-CDV and OP-CDV differed considerably from the other three
      strains. Moreover, an additional second open reading frame was detected in the
      'non-coding' region of the M gene in the wild A75-CDV, the two tissue culture
      adapted CDV strains and SH-CDV, but not in OP-CDV. The presence of this
      additional open reading frame correlated with the ability to cause a spontaneous
      persistent infection in vitro. Our findings support the notion that both N- and M
      genes of CDV harbor determinants of viral persistence.

PMID- 9231984
TI  - The time course of the specific antibody response by various ELISAs in pigs
      experimentally infected with Toxoplasma gondii.
AB  - With the aim of developing routine serological tests for monitoring the
      Toxoplasma infection status of Danish swine herds, four ELISAs based on
      tachyzoite antigen were set up: (1) an indirect ELISA for IgG-antibody; (2) a
      blocking ELISA for antibody to the membrane antigen, P30; (3) an indirect ELISA
      for IgM; (4) a reverse, antibody-catching IgM-ELISA. Groups of pigs (number
      between 6 and 10) were inoculated with tachyzoites of the RH-strain, tissue cysts
      of two complete strains, or oocysts in two doses (10(3) and 10(4). All
      inoculations were tolerated well. Irrespective of strain and stage used for
      inoculation, specific IgG and anti-P30 blocking activity appeared after 1-2
      weeks, with OD-values stabilizing after 3-6 weeks and persisting throughout the
      study period (3-4 months). Specific IgM appeared quickly, but was short-lived
      (approximately 2 weeks). A cut-off OD-value of 0.36 for positive seroreaction in
      the indirect IgG-ELISA was determined on the basis of 69 sera from four herds,
      investigated in the dye-test (serum dilution 1:10) and ELISA. The chosen cut-off
      gave optimal combined sensitivity and specificity of 0.94 and 0.92, respectively,
      using the dye-test as a standard. Corresponding figures for the blocking ELISA
      were 37% inhibition as cut-off, with sensitivity and specificity of 0.94 and
      0.94, respectively. Sera from a total of 87 pigs, experimentally infected with
      bacteria of the genera Salmonella, Yersinia or Actinobacillus and with the
      parasites Isospora suis, Trichinella spiralis or Ascaris suum, in no case
      produced cross-reactions in the IgG-ELISA. However, 3/9 pigs inoculated with 50
      000 sporocysts of Sarcocystis miescheriana gave maximal OD-readings of 0.40-0.45
      during the 13-15 weeks observation period. None of the sera from heterologously
      infected animals produced inhibitions in the anti-P30 blocking ELISA exceeding
      36%.

PMID- 9231985
TI  - An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies
      against Babesia bovis in cattle.
AB  - A method for the isolation of Babesia bovis merozoites from infected erythrocytes
      (Machado et al., 1994) and an enzyme-linked immunosorbent assay (ELISA) for the
      detection of anti-B. bovis antibodies were developed. This ELISA utilizes a
      soluble, alkali-digested B. bovis antigen. Sera from calves experimentally
      infected with B. bovis were screened by this technique from day 9 to day 233
      postinfection (PI). Maximum titers were reached between days 29 and 149 PI. Sera
      from calves (n = 62), heifers (n = 38) and cows (n = 49), raised in tick-infested
      areas of Sao Paulo State, showed higher antibody levels in heifers and cows. A
      higher percentage of negative sera (19.4%) was found among calves. Sodium dodecyl
      sulphate-polyacrylamide electrophoresis (SDS-PAGE) and immunoblotting have
      identified proteins of similar molecular mass in the two species. Sera from
      calves experimentally infected with B. bovis reacted with homologous antigens at
      the level of 95, 66 and 23 kDa. The same serum reacted with the 23 kDa band of
      heterologous antigen. Sera from calves experimentally infected with B. bigemina
      recognized 82, 66, 58, 36 and the 23 kDa polypeptides of homologous and
      heterologous antigens. The experimental ELISA described may prove to be a
      practical serological test for bovine Babesia infection with the choice of
      specific test antigen for B. bovis and B. bigemina.

PMID- 9231986
TI  - Cross-infection of moose (Alces alces) and reindeer (Rangifer tarandus) with
      Elaphostrongylus alces and Elaphostrongylus rangiferi (Nematoda,
      Protostrongylidae): effects on parasite morphology and prepatent period.
AB  - Moose (Alces alces) and reindeer (Rangifer tarandus) were experimentally cross
      infected with Elaphostrongylus rangiferi and Elaphostrongylus alces,
      respectively. Both Elaphostrongylus species completed their development in the
      alternate hosts but produced fewer larvae than in their usual host species.
      Reindeer infected with Elaphostrongylus alces developed patent infections after
      39-130 days. In moose, the prepatent period of this parasite was 39-73 days.
      Elaphostrongylus rangiferi infections were patent in moose after 133 days. The
      male morphological characteristic of E. alces in moose and reindeer, and E.
      rangiferi in moose and their migration pattern retained regardless of the host
      species. These results provide further evidence that E. alces and E. rangiferi
      are two distinct species.

PMID- 9231987
TI  - Persistence of immunity of Nematodirus battus infection in lambs.
AB  - Fifty-four Greyface Suffolk lambs aged 3 months were allocated to six groups of
      seven and one group of 12. Three groups were infected continuously with
      Nematodirus battus larvae (L3) over a 7-week period and three groups remained
      worm-free. One week after the last larval dose all six groups were treated with
      anthelmintic and challenged with a single dose of 30,000 N. battus L3 either 1, 6
      or 12 weeks post-treatment (PT) and killed 10 days later. A seventh continuously
      infected and treated group (n = 12) was segregated into four sub-groups of three
      lambs which were used as tissue cell count controls and provided data on local
      cellular responses prior to challenge. Lambs in the first sub-group were killed
      immediately after anthelmintic treatment and those in the other sub-groups were
      killed on the same day that the lambs in the other main groups were challenged.
      Overall post-challenge worm burdens did not differ significantly between
      previously infected and challenge control groups although they were significantly
      reduced in both treatment groups by Week 12 PT. The principal manifestation of
      acquired immunity that was maintained throughout 12 weeks without further
      infection was retardation in larval development. There was also evidence of
      preferential rejection of male worms from immune lambs. Local mast cell, but not
      eosinophil, responses were significantly enhanced by previous infection and
      persisted up to Week 12 PT. The numbers of bone marrow eosinophils were
      significantly increased as a result of previous infection and this response
      persisted up to Week 12 PT. During primary infection anti-L4 and anti-adult worm
      IgG responses were significantly increased in the previously infected lambs by
      Day 42 post-infection. Eosinophil responses during this period did not differ
      between groups. The inflammatory cell responses, coupled with the parasitological
      observations, suggest that immunity to previous infection is maintained for up to
      12 weeks PT without further antigenic stimulation. This 'immunological memory'
      may have waned partially after 6 weeks PT although the superimposition of age
      resistance may have masked the effect.

PMID- 9231988
TI  - Mitogenic stimulation of bovine peripheral blood mononuclear cells by Theileria
      sergenti antigen and inhibition by antibody from experimentally infected cattle.
AB  - Stimulation with a lysate of Theileria sergenti-parasitized red blood cells
      (PRBC) resulted in marked proliferation of normal bovine peripheral blood
      mononuclear cells (PBMC) in vitro. Partial inhibition of the proliferation was
      demonstrated by the addition of immunoglobulin (Ig) obtained from experimentally
      infected cattle when they revealed high levels of parasitemia and antibody
      titres. A mouse monoclonal antibody recognizing a 32 kDa antigen also showed
      inhibitory activity against the in vitro proliferation of bovine PBMC, but
      complete inhibition could not be achieved.

PMID- 9231989
TI  - Sudden death due to Paragonimus kellicotti infection in a dog.
AB  - A sudden death due to Paragonimus kellicotti infection in a dog that had had no
      previous clinical signs of illness until the day of admission to the veterinary
      hospital is documented. The clinical, haematological and biochemical
      abnormalities, as well as postmortem findings, are presented. This report
      represents the first case of canine paragonimiasis in Israel, and discusses the
      possibility of this fluke becoming established in the Middle East.

PMID- 9231990
TI  - Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a
      longitudinal study in patients treated with interferon-alpha.
AB  - The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte
      associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and
      sCD58) in human sera. Data concerning their role in chronic liver disease and
      their usefulness in disease monitoring are contradictory. We addressed the
      question whether elevated sCD54/sCD58 correlated either with disease activity or
      with decreased elimination secondary to reduced liver function in chronic
      hepatitis B. We studied 31 patients with chronic hepatitis B undergoing
      interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54
      and sCD58 were measured at four weeks interval by specific Sandwich ELISA during
      a follow-up period of ten months. The maximal difference in concentration of each
      biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was
      determined for each patient during the whole follow-up period. These differences
      were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58)
      at the respective time points. Using this method, we were able to eliminate
      interindividual differences in serum concentrations for sCD54 and sCD58 and to
      avoid bias due to preselection of patients. We found that delta sCD54 correlated
      with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such
      correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58
      levels. Neither hepatitis B viremia nor the immune response to hepatitis B during
      the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58
      levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and
      delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation
      was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings
      imply that sCD54 and sCD58 may be associated with a decrease in liver function
      that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful
      to monitor disease activity or response to interferon therapy in chronic
      hepatitis B. From our data we conclude, that decreased elimination of soluble
      adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible
      for increased serum concentrations detected.

PMID- 9231991
TI  - Cardiac tamponade--a rare complication in acute pancreatitis.
AB  - A patient with recurrent acute pancreatitis developed pericardial effusion and
      cardiac tamponade. His systolic blood pressure fell to 70 mmHg and sinus
      tachycardia (150/min) developed. The central venous pressure rose from 3 cm H2O
      to 27 cm H2O. A chest radiograph showed an enlargement of the cardiac shadow.
      Pericardial paracentesis was performed and 300 ml fluid was aspirated. This
      produced rapid clinical improvement. The literature related to this uncommon
      complication is reviewed and possible pathogenetic mechanisms are discussed.

PMID- 9231992
TI  - Fulminant primary manifestation of Crohn's colitis "Hot Crohn's disease".
AB  - Following the very short course of a disease with watery diarrhea, fever, nausea,
      meteorism and a severe feeling of general illness, a 22-year-old patient was
      diagnosed as having a toxic megacolon, and a subtotal colectomy was carried out.
      The postoperative progression was uncomplicated and the patient recovered
      quickly. The examination of the operation specimen revealed a serious ulcerous
      colitis with relative omission of the rectum and the distal sigmoid colon. After
      critical evaluation of the histological findings, it was judged to be a fulminant
      Crohn's colitis and, for the purposes of differential diagnosis, differentiated
      from ulcerative colitis and colitis indeterminate. The formal pathogenesis of the
      inflammatory-ulcerous processes is discussed, in particular with regard to the
      activation of the macrophages and the very short anamnesis in a clinically
      established primary manifestation of the disease.

PMID- 9231993
TI  - The influence of posttreatment mutual help group participation on the friendship
      networks of substance abuse patients.
AB  - The effect of 12-step mutual help groups (e.g., Narcotics Anonymous) on members'
      friendship networks has received little attention. This 1-year longitudinal study
      examined such effects in a sample of 2,337 male substance abuse inpatients, 57.7%
      of whom became significantly involved in 12-step activities (e.g., reading
      program literature, attending meetings) after treatment. An a priori model of the
      interplay of 12-step involvement) and friendship networks was tested using
      structural equation modeling, and found to have excellent fit to the data. Twelve
      step group involvement after treatment predicted better general friendship
      characteristics (e.g., number of close friends) and substance abuse-specific
      friendship characteristics (e.g., proportion of friends who abstain from drugs
      and alcohol) at follow-up. Results are discussed in terms of how mutual help
      group involvement benefits patients and how the self-help group evaluation
      paradigm should be broadened.

PMID- 9231994
TI  - Assessment of major life events for Hong Kong adolescents: the Chinese Adolescent
      Life Event Scale.
AB  - Previous Chinese research on adolescent life stress adopted life event scales
      that were directly translated from Western measures. To address the
      methodological and cultural issues overlooked by the "import" approach, the
      present research aimed at constructing a life event scale for Hong Kong
      adolescents. Study 1 was conducted to congregate items for the Chinese Adolescent
      Life Event Scale (CALES). The CALES contains 44 items derived from 618 Hong Kong
      adolescents. Study 2 revealed adequate test-retest reliability and criterion
      related validity for the CALES. Moreover, the CALES yielded stronger
      relationships with depression than did the translated life event measures.
      Results suggest that the CALES is appropriate for assessing life events for Hong
      Kong adolescents. Both unique features of the CALES and life events found only in
      the translated measures are examined. Implications for Chinese research on life
      stress are discussed.

PMID- 9231995
TI  - Informal caregiving to persons with AIDS in the United States: caregiver burden
      among central cities residents eighteen to forty-nine years old.
AB  - Characteristics and caregiving experiences of friends and family members caring
      for people with AIDS (PWAs) were examined. Based on a probability sample of
      informal AIDS caregivers ages 18-49 living in central cities of the United States
      (n = 260), analyses were conducted to (a) identify the sociodemographic
      characteristics of young central city caregivers; and (b) examine the effects of
      caregiver characteristics (relationship to PWA, gender, race/ethnicity, income,
      sexual orientation, HIV status, perceived susceptibility), and level of objective
      caregiving demands, on subjective caregiver burden. Results indicate that the
      largest group of caregivers in this age category are male friends of the PWA--a
      group not typically found among caregivers to persons with other types of
      illnesses. In general, gay or bisexual caregivers, caregivers who have
      traditional family ties to the PWA, men relative to women, and lower income
      caregivers, report the greatest burden. While level of caregiving demands
      represents the most influential predictor of caregiver burden, white and male
      caregivers experience greater burden, independent of level of involvement and
      other caregiver characteristics. Receiving instrumental support with caregiving
      buffers the impact of high objective demands on subjective burden.

PMID- 9231996
TI  - Control beliefs and faith as stress moderators for Korean American versus
      Caucasian American protestants.
AB  - Examined relationships among negative life events, four locus of control
      attributions (Internality, Powerful Others, Chance and God Control), and
      psychological distress for Korean American versus Caucasian American Protestants.
      Negative events and Powerful Others beliefs were positively related to distress,
      whereas Internality was negatively related to distress. Ethnicity and God Control
      interacted: The relationship between God Control beliefs and anxiety was negative
      for Caucasians but positive for Koreans. Three-way interactions (Ethnicity x
      Locus of Control x Negative Events) also emerged. As Caucasians' Powerful Others
      beliefs increased, the positive relationship between negative events and
      depression became stronger; Koreans' Powerful Others beliefs had no such effect.
      As Caucasians' God Control beliefs increased, the negative event-depression
      relationship changed from positive to negative; the reverse was true for Koreans.
      Findings support the value of assessing ethnoculture and religiousness in
      stressful life events research.

PMID- 9231997
TI  - The experience of caregiving among mothers of adults suffering from psychotic
      disorders: factors associated with their psychological distress.
AB  - To identify correlates of psychological distress among multiple indicators, 99
      women with adult children suffering from a psychotic disorder were interviewed.
      The women, who were recruited through hospitals and self-help groups, represented
      different socioeconomic levels. A face-to-face standardized interview was
      conducted, mainly in the participants' homes. Multiple hierarchical regression
      analysis showed that dimensions of burden and social support were strongly
      associated with distress reported by the participants. The negative interactions
      that participants had with their main confidant or spouse constituted a more
      powerful correlate than their perception of the quality of this relationship.
      Furthermore, a perception of their own health as poorer is a strong correlate of
      their distress. Since no control group was studied simultaneously, these results
      suggest, but do not prove, the presence of differences between mothers of adults
      with psychotic disorders and other mothers.

PMID- 9231999
TI  - Concentrations of selected contaminants in cabin air of airbus aircrafts.
AB  - The concentrations of selected air quality parameters in aircraft cabins were
      investigated including particle numbers in cabin air compared to fresh air and
      recirculation air, the microbiological contamination and the concentration of
      volatile organic compounds (VOC). The Airbus types A310 of Swissair and A340 of
      Lufthansa were used for measurements. The particles were found to be mainly
      emitted by the passengers, especially by smokers. Depending on recirculation
      filter efficiency the recirculation air contained a lower or equal amount of
      particles compared to the fresh air, whereas the amount of bacteria exceeded
      reported concentrations within other indoor spaces. The detected species were
      mainly non-pathogenic, with droplet infection over short distances identified as
      the only health risk. The concentration of volatile organic compounds (VOC) were
      well below threshold values. Ethanol was identified as the compound with the
      highest amount in cabin air. Further organics were emitted by the passengers--as
      metabolic products or by smoking--and on ground as engine exhaust (bad airport
      air quality). Cleaning agents may be the source of further compounds.

PMID- 9231998
TI  - Ethnocultural differences in prevalence of adolescent depression.
AB  - Data from an ethnically diverse sample of middle school (Grades 6-8) students (n
      = 5,423) are analyzed for ethnic differences in major depression. The point
      prevalence of major depression was 8.4% without and 4.3% with impairment. Data
      were sufficient to calculate prevalences for nine ethnic groups. Prevalences
      adjusted for impairment ranged from 1.9% for youths of Chinese descent to 6.6%
      for those of Mexican decent. African and Mexican American youths had
      significantly higher crude rates of depression without impairment, but only the
      latter had significantly higher rates of depression with impairment. Multivariate
      (logistic regression) analyses, adjusting for the effects of age, gender, and
      socioeconomic status (SES), yielded significant odds ratios for only one group.
      Mexican American youths were at elevated risk for both depression without (OR =
      1.74, p < .05) and depression with impairment (OR = 1.71, p < .05). There was no
      significant interaction of ethnicity and SES in relation to depression. Females
      had higher prevalences of depression with and without impairment, as did youths
      who reported that their SES was somewhat or much worse off than their peers. The
      data add to growing evidence that Mexican American youths are at increased risk
      of depression, and that community intervention efforts should specifically target
      this high-risk group.

PMID- 9232000
TI  - S-triazine residues in groundwater.
AB  - In the last years, the occurrence of pesticides and other chemicals in
      groundwater has been confirmed. The herbicide atrazine is among the pesticides
      most frequently detected in groundwater. In groundwater samples from the United
      States atrazine concentrations reached levels up to 10 micrograms/1. In our
      lysimeter experiments with radioactive labelled terbuthylazine we measured 2.87
      4.20% of the applied radioactivity after 1160 days in the leachate.

PMID- 9232001
TI  - Phospholipid fatty acid profiles in selected members of soil microbial
      communities.
AB  - Fatty acids derived from phospholipids and lipopolysaccharides were investigated
      from 33 taxonomically different organisms (bacteria, fungi and plant cells) known
      a priori to inhabit soil (except E. coli). The extended extraction procedure
      used, liberated non-ester-linked fatty acids in addition to ester-linked fatty
      acids, hydroxy substituted fatty acids in three different fractions. The amount
      of non-ester-linked fatty acids was as high as 70% of the total phospholipid
      fatty acids in some fungi and varied considerably in different organisms. The cis
      vaccenic acid constituted about 50% of phospholipid fatty acids in selected
      bacteria belonging to the alpha subclass of Proteobacteria. These fatty acids
      were not found in other selected organisms. A large amounts of branched chain
      fatty acids were found in various organisms. If the branching are localised on
      positions other than iso and anteiso they were strong indicators for gram
      positive bacteria. The cyclopropyl fatty acids are mainly localized in gram
      negative bacteria. The beta hydroxy fatty acid of the outer membrane are
      widespread among bacterial taxa and fungi. These fatty acids are not recommended
      to use as "signature" fatty acids for gram negative bacteria.

PMID- 9232002
TI  - Physiological basis in the assessment of ecotoxicity of pesticides to soil
      organisms.
AB  - Earthworms are universally accepted as one of the most suitable and
      representative soil animals to be used for assessing chemical pollution in soils.
      Therefore, in this work earthworm species diverse in habitat and life-pattern are
      used and the effects of sublethal concentrations of terbuthylazine and carbofuran
      on the reproductive processes, respiration and excretion are investigated. The
      results show that even low and moderate concentrations of the pesticides can
      induce measurable physiological effects. Species-specific and substance-specific
      effects are noticeable in the worms.

PMID- 9232003
TI  - Behaviour and ecotoxicology of aluminium in soil and water--review of the
      scientific literature.
AB  - The scientific literature on chemical and biological behaviour of aluminium
      products and aluminium compounds following exposure to environmental media is
      considered. Although many studies have been performed on corrosion of aluminium
      products, no precise information exists about the amount of aluminium released by
      dissolution of the protective layer of aluminium products. Since no data are
      available on the effect caused by introduction of anthropogenic aluminium into
      the environment a comparison between aluminium released as a result of human
      activity and geogenic aluminium is only possible by estimating the extent to
      which anthropogenic aluminium is released using purely theoretical premises. The
      important results in the literature about the availability and toxicological
      effects of metallic aluminium and aluminium compounds are presented. Finally, a
      general assessment of the environmental compatibility of aluminium products is
      given.

PMID- 9232004
TI  - Ionic composition of endolymph in teleosts: origin and importance of endolymph
      alkalinity.
AB  - Ionic (Na+, K+, Cl-, PO4(3-), pH), total CO2, total calcium and protein
      concentrations in the plasma and endolymph of the inner ear were compared in
      trout Oncorhynchus mykiss and turbot Scophthalmus maximus. In both species,
      saccular endolymph was characterized by high levels of K+ and total CO2 and in
      trout by an alkaline pH. The kinetic characteristics of proton secretion across
      the saccular epithelium of trout were investigation using a titration technique
      in which isolated saccules were mounted as closed sacs. The rate of proton
      secretion depends strongly on the pH of the Ringer's solution and secretion stops
      at a pH below 7.2. Proton secretion is driven by an energy-dependent mechanism
      involving basolateral ouabain-sensitive Na+/K+ exchangers. Proton secretion was
      partially inhibited by acetazolamide and completely inhibited in Na(+)-free
      Ringer or in the presence of 1 mmol l-1 amiloride. A cellular model stressing the
      importance of proton exchange through the saccular epithelium is proposed to
      explain the regulation of endolymph pH, a crucial factor for the deposition of
      otolith calcium.

PMID- 9232005
TI  - Role for adenosine in channel arrest in the anoxic turtle brain.
AB  - The remarkable ability of the turtle brain to survive anoxia is based on its
      ability to match energy demand flexibly to energy production. Earlier studies
      indicate that reduced ion leakage is an important mechanism for energy
      conservation during anoxia. We tested the hypothesis that extracellular adenosine
      plays a role in the reduction of K+ flux (channel arrest) that occurs in the
      anoxic turtle brain. Changes in extracellular K+ concentration ([K+]o in the in
      situ brain of the turtle Trachemys scripta were monitored following inhibition of
      Na+/K(+)-ATPase with ouabain. The time to reach full depolarization ([K+]o
      plateau) was three times longer in the anoxic brain than in normoxic controls and
      the initial rate of K+ leakage was reduced by approximately 70%. Superfusing the
      brain before the during anoxia with the general adenosine receptor blocker
      theophylline, or the specific adenosine A1 receptor blocker 8
      cyclopentyltheophylline, significantly shortened the time to full depolarization
      in the ouabain-challenged anoxic brain and increased the rate of K+ efflux. The
      results suggest that adenosine A1 receptors are involved in the expression of
      anoxia-induced ion channel arrest in the turtle brain.

PMID- 9232006
TI  - Three-dimensional kinematics and limb kinetic energy of running cockroaches.
AB  - We tested the hypothesis that fast-running hexapeds must generate high levels of
      kinetic energy to cycle their limbs rapidly compared with bipeds and quadrupeds.
      We used high-speed video analysis to determine the three-dimensional movements of
      the limbs and bodies of cockroaches (Blaberus discoidalis) running on a motorized
      treadmill at 21 cm s-1 using an alternating tripod gait. We combined these
      kinematic data with morphological data to calculate the mechanical energy
      produced to move the limbs relative to the overall center of mass and the
      mechanical energy generated to rotate the body (head + thorax + abdomen) about
      the overall center of mass. The kinetic energy involved in moving the limbs was 8
      microJ stride-1 (a power output of 21 mW kg-1, which was only approximately 13%
      of the external mechanical energy generated to lift and accelerate the overall
      center of mass at this speed. Pitch, yaw and roll rotational movements of the
      body were modest (less than +/- 7 degrees), and the mechanical energy required
      for these rotations was surprisingly small (1.7 microJ stride-1 for pitch, 0.5
      microJ stride-1 for yaw and 0.4 microJ stride-1 for roll) as was the power (4.2,
      1.2 and 1.1 mW kg-1, respectively). Compared at the same absolute forward speed,
      the mass-specific kinetic energy generated by the trotting hexaped to swing its
      limbs was approximately half of that predicted from data on much larger two- and
      four-legged animals. Compared at an equivalent speed (mid-trotting speed), limb
      kinetic energy was a smaller fraction of total mechanical energy for cockroaches
      than for large bipedal runners and hoppers and for quadrupedal trotters.
      Cockroaches operate at relatively high stride frequencies, but distribute ground
      reaction forces over a greater number of relatively small legs. The relatively
      small leg mass and inertia of hexapeds may allow relatively high leg cycling
      frequencies without exceptionally high internal mechanical energy generation.

PMID- 9232007
TI  - Working memory and on-line sentence comprehension in patients with Alzheimer's
      disease.
AB  - We examined the ability of patients with dementia of the Alzheimer's type (DAT)
      and normal controls to perform a sentence acceptability judgment task that
      required determining the referent for a reflexive pronoun. Performance on three
      different sentence types that differed in terms of syntactic complexity was
      assessed. Subjects performed the task alone and under two different dual-task
      conditions which required continuous, externally paced responses. DAT patients
      were more affected than controls by the dual-task conditions, but were not
      disproportionately impaired on the more complex sentence types. The failure of
      DAT patients to be disproportionately affected on the most complex sentence types
      in the dual-task conditions provides evidence for the separation of the
      processing resources that are used in sentence comprehension from those involved
      in other tasks.

PMID- 9232008
TI  - Language generation in schizophrenia and mania: the relationships among
      verbosity, syntactic complexity, and pausing.
AB  - We examined the relationships among verbosity, syntactic complexity, and pausing
      in the speech of 21 Diagnostic and Statistical Manual of Mental Disorders (3rd
      ed., rev.) (DSM-III-R) diagnosed schizophrenic participants and 19 DSM-III-R
      diagnosed manic participants. We found that less verbosity was associated with
      both less syntactic complexity and greater pausing. In addition, less syntactic
      complexity was associated with greater pausing. The strength of these
      associations did not differ significantly between the two diagnostic groups. We
      propose that deficits in verbosity, syntactic complexity, and pausing are all
      related to a disturbance in message generation. We discuss the consistency of
      this hypothesis with previous research linking information processing and frontal
      lobe deficits to disturbances in verbosity, syntactic complexity, and pausing.

PMID- 9232009
TI  - The continuum of deep/surface dyslexia.
AB  - A right-handed male sustained traumatic brain injury which resulted in anomia,
      dyslexia and agraphia. The most severe CT (computed tomography)-identified brain
      damage was located in the right parieto-temporal lobe. In the first months
      following the injury, the pattern of reading errors was similar to that
      associated with deep dyslexia. However, nonlexical derivation of phonology from
      print was not abolished. As the patient's ability to associate letter patterns
      with sounds improved, oral reading also improved. Although he no longer produced
      semantic errors in oral reading, he continued to produce oral reading errors that
      were visually and phonologically related to the targets. Four months after the
      injury, the error pattern observed in the patient's oral reading was consistent
      with very mild surface dyslexia. The significance of these observations to dual
      deficit models of acquired dyslexia is discussed, as are their implications for
      rehabilitation.

PMID- 9232010
TI  - Spontaneous imitation of fundamental frequency and speech rate by nonstutterers
      and stutterers.
AB  - Speech can be described either in terms of acoustics, as a perceptual outcome, or
      as a motor event. Central to theories of speech perception and production is an
      attempt to describe how these aspects of speech are interrelated. The present
      experiment investigated how the nonstutterers' and stutterers' reproductions of
      acoustically presented interrogative sentences were influenced by experimental
      variations of intonation (sentence initial vs. sentence final) and speech rate
      (normal vs. time compressed). We studied the effects of these stimulus
      manipulations on the speech rate and fundamental frequency (F0) of 10 adult
      German-speaking nonstutterers and seven stutterers. Experimental manipulations of
      intonation and speech rate significantly influenced the syllable duration and
      speech rate of both normal speakers and stutterers. The fundamental frequency of
      the subjects' responses were also significantly influenced by the intonation of
      the stimulus. But the stutterers' increase in F0 for stressed syllables was
      generally less pronounced than that of nonstutterers. These results imply that
      (a) the subject not only extract linguistic meaning from intonation but that they
      also store extragrammatical speech rate information, and (b) the speakers adopt
      these speech rate variations for their own productions. Generally, these results
      demonstrate that speech perception is not limited to extracting linguistically
      invariant information. The results show that speakers actively generate their own
      prosody and that this generative process is influenced by the prosodic structure
      of another speaker's antecedent speech. The implications of these results for
      theories of speech production are discussed.

PMID- 9232012
TI  - Comparing estimates of the effects of air pollution on human mortality obtained
      using different regression methodologies.
AB  - Studies using regression techniques report their results using a variety of
      statistics. Evaluation of the consistency of findings, such as in a metaanalysis,
      requires calculating the statistical estimates of the effect reported in each
      study in a comparable manner. In this paper, we consider multiple linear
      regression, multiple Poisson regression, and logistic regression estimates. We
      present results that are needed to calculate, on a common basis, the slope of the
      regression function at a specified value, the elasticity function of the
      regression function at a specified value, the relative risk at a specified value,
      and the odds ratio at a specified value. We apply these results to studies of the
      association of daily mortality in an area to the daily air pollution level of
      ozone and PM10. We calculate the estimated slope of the number of deaths per
      billion population associated with an increase of 1 ppb of ozone level in studies
      of daily mortality in three urban areas. These studies, in Los Angeles, New York,
      and St. Louis, produced very comparable results on a common basis, especially
      when compared to the coefficients as reported. We also calculated the estimated
      elasticity function of the daily mortality and daily PM10 level for eight areas
      and found that the elasticities varied within a factor of roughly two, much less
      than the variability in the coefficients as reported.

PMID- 9232011
TI  - Reading in Arabic orthography: the effect of vowels and context on reading
      accuracy of poor and skilled native Arabic readers in reading paragraphs,
      sentences, and isolated words.
AB  - This study investigated the effect of vowels and context on the reading accuracy
      of poor and skilled native Arabic readers in reading paragraphs, sentences, and
      words. Central to this study is the belief that reading theory today should
      consider additional variables, especially when explaining the reading process in
      Arabic orthography among poor and normal/skilled readers. This orthography has
      not been studied. Reading theory today is the sum of conclusions from studies
      conducted in Latin orthography. The subjects were 77 native Arabic speakers, 34
      of them poor readers and 44 normal/skilled readers. The subjects had to read in
      Arabic 15 paragraphs, 60 sentences, and 210 words. There were three reading
      conditions: fully vowelized, partially vowelized, and unvowelized texts. The
      results showed that vowels and contexts were important variables to facilitate
      word recognition in poor and normal/skilled readers in Arabic orthography.

PMID- 9232013
TI  - Compliance versus risk in assessing occupational exposures.
AB  - Assessments of occupational exposures to chemicals are generally based upon the
      practice of compliance testing in which the probability of compliance is related
      to the exceedance [gamma, the likelihood that any measurement would exceed an
      occupational exposure limit (OEL)] and the number of measurements obtained. On
      the other hand, workers' chronic health risks generally depend upon cumulative
      lifetime exposures which are not directly related to the probability of
      compliance. In this paper we define the probability of "overexposure" (theta) as
      the likelihood that individual risk (a function of cumulative exposure) exceeds
      the risk inherent in the OEL (a function of the OEL and duration of exposure). We
      regard theta as a relevant measure of individual risk for chemicals, such as
      carcinogens, which produce chronic effects after long-term exposures but not
      necessarily for acutely-toxic substances which can produce effects relatively
      quickly. We apply a random-effects model to data from 179 groups of workers,
      exposed to a variety of chemical agents, and obtain parameter estimates for the
      group mean exposure and the within- and between-worker components of variance.
      These estimates are then combined with OELs to generate estimates of gamma and
      theta. We show that compliance testing can significantly underestimate the health
      risk when sample sizes are small. That is, there can be large probabilities of
      compliance with typical sample sizes, despite the fact that large proportions of
      the working population have individual risks greater than the risk inherent in
      the OEL. We demonstrate further that, because the relationship between theta and
      gamma depends upon the within- and between-worker components of variance, it
      cannot be assumed a priori that exceedance is a conservative surrogate for
      overexposure. Thus, we conclude that assessment practices which focus upon either
      compliance or exceedance are problematic and recommend that employers evaluate
      exposures relative to the probabilities of overexposure.

PMID- 9232014
TI  - Exploring the "psychometric paradigm": comparisons between aggregate and
      individual analyses.
AB  - The "psychometric paradigm" developed by Slovic, Fischhoff, and Lichtenstein was
      a landmark in research about public attitudes toward risks. One problem with
      work, however, was that (at least initially) it did not attempt to distinguish
      between individuals or groups of people, except "experts" vs. "lay people." This
      paradigm produced a "cognitive map" of hazards, and the assumption seemed to be
      that the characteristics identified were inherent attributes of risk. This paper
      examines the validity of this assumption. A questionnaire survey similar to those
      designed by Slovic et al. was conducted, but the data were analyzed at both the
      aggregate level, using mean scores, and at the level of individuals (N = 131
      Norwich residents). The results reported here demonstrate that (1) individuals
      vary in their perception of the same risk issue; (2) individuals vary in their
      rating of the same risks characteristics on the same risk issue; and (3) some of
      the strong intercorrelations observed between risk characteristics at the
      aggregate level are not supported when the same data are analysed at the level of
      individuals. Despite these findings, the relationship between risk
      characteristics and risk perceptions inferred by the psychometric paradigm did
      hold true at the level of individuals, for most--but not all--of the
      characteristics. In particular, the relationship between "lack of knowledge to
      those exposed" and risk perceptions appears to be a complex one, a finding which
      has important implications for risk communication strategies.

PMID- 9232015
TI  - Risk perception, federal spending, and the Savannah River Site: attitudes of
      hunters and fishermen.
AB  - This paper examines the attitudes of 285 hunters and fishermen from South
      Carolina about hunting and fishing, risk, environmental issues, and future land
      use of the Savannah River Site, We test the null hypothesis that there is no
      difference in hunting and fishing rates, attitudes toward the safety of fish and
      deer obtained from SRS, attitudes toward future land use at SRS, and perceptions
      of the severity of environmental problems as a function of how far respondents
      lived from the site. Respondents hunted or fished an average of over 40 days a
      year, and only half felt that the fish and deer from SRS were safe to eat.
      Willingness to expend federal funds was correlated with perceptions of the
      severity of the problem. Preferences for future land use at SRS fell into three
      categories: high (environmental research park, hunting, fishing, camping), medium
      (nuclear production, factories, preserve only), and low (nuclear waste storage,
      residential). There were no differences in hunting and fishing rates, ranking of
      the severity of environmental problems, and willingness to expend federal funds
      as a function of distance of residence from SRS, but attitudes toward future land
      use differed significantly as a function of location of residence. Those living
      close to SRS were more willing to have the site used for factories, residential,
      nuclear material production and to store nuclear wastes than those living farther
      from the site. Our data on recreational rates, attitudes toward future land use,
      and willingness to expend federal funds to solve environmental problems reiterate
      the importance of assessing stakeholder attitudes toward decisions regarding
      future land use at DOE sites.

PMID- 9232016
TI  - Categorical regression analysis of acute exposure to tetrachloroethylene.
AB  - Exposure-response analysis of acute noncancer risks should consider both
      concentration (C) and duration (T) of exposure, as well as severity of response.
      Stratified categorical regression is a form of meta-analysis that addresses these
      needs by combining studies and analyzing response data expressed as ordinal
      severity categories. A generalized linear model for ordinal data was used to
      estimate the probability of response associated with exposure and severity
      category. Stratification of the regression model addresses systematic differences
      among studies by allowing one or more model parameters to vary across strata
      defined, for example, by species and sex. The ability to treat partial
      information addresses the difficulties in assigning consistent severity scores.
      Studies containing information on acute effects of tetrachloroethylene in rats,
      mice, and humans were analyzed. The mouse data were highly uncertain due to lack
      of data on effects of low concentrations and were excluded from the analysis. A
      model with species-specific concentration intercept terms for rat and human
      central nervous system data improved fit to the data compared with the base model
      (combined species). More complex models with strata defined by sex and species
      did not improve the fit. The stratified regression model allows human effect
      levels to be identified more confidently by basing the intercept on human data
      and the slope parameters on the combined data (on a C x T plot). This analysis
      provides an exposure-response function for acute exposures to tetrachloroethylene
      using categorical regression analysis.

PMID- 9232017
TI  - Perception of ecological risk to water environments.
AB  - This paper examines lay and expert perceptions of the ecological risks associated
      with a range of human activities that could adversely affect water resource
      environments. It employs the psychometric paradigm pioneered in characterizing
      perceptions of human health risks, which involves surveys to obtain judgments
      from subjects about risk items in terms of several important characteristics of
      the risks. The paper builds on a previous study that introduced ecological risk
      perception. This second study employs a larger, more diverse sample, a more
      focused topic area, and comparisons between lay and expert judgments. The results
      confirm that a small set of underlying factors explain a great deal of
      variability in lay judgments about ecological risks. These have been termed
      Ecological Impact, Human Benefits, Controllability, and Knowledge. The results
      are useful in explaining subjects' judgments of the general riskiness of, and
      need for regulation of, various risk items. The results also indicate several
      differences and areas of agreement among the lay and expert samples that point to
      potential key issues in future ecological risk management efforts for water
      resources.

PMID- 9232018
TI  - Estimating health risks from natural hazards using risk assessment and
      epidemiology.
AB  - Risk assessment is the process of estimating the likelihood that an adverse
      effect may result from exposure to a specific health hazard. The process
      traditionally involves hazard identification, dose-response assessment, exposure
      assessment, and risk characterization to answer "How many excess cases of disease
      A will occur in a population of size B due to exposure to agent C at dose level
      D?" For natural hazards, however, we modify the risk assessment paradigm to
      answer "How many excess cases of outcome Y will occur in a population of size B
      due to natural hazard event E of severity D?" Using a modified version involving
      hazard identification, risk factor characterization, exposure characterization,
      and risk characterization, we demonstrate that epidemiologic modeling and
      measures of risk can quantify the risks from natural hazard events. We further
      extend the paradigm to address mitigation, the equivalent of risk management, to
      answer "What is the risk for outcome Y in the presence of prevention intervention
      X relative to the risk for Y in the absence of X?" We use the preventable
      fraction to estimate the efficacy of mitigation, or reduction in adverse health
      outcomes as a result of a prevention strategy under ideal circumstances, and
      further estimate the effectiveness of mitigation, or reduction in adverse health
      outcomes under typical community-based settings. By relating socioeconomic costs
      of mitigation to measures of risk, we we illustrate that prevention effectiveness
      is useful for developing cost-effective risk management options.

PMID- 9232019
TI  - The two-stage model of carcinogenesis: overcoming the nonidentifiability dilemma.
AB  - The two-stage mathematical model of carcinogenesis has been shown to be
      nonidentifiable whenever tumor incidence data alone is used to fit the model
      (Hanin and Yakovlev, 1996). This lack of identifiability implies that more than
      one parameter vector satisfies the optimization criteria for parameter
      estimation, e.g., maximum likelihood estimation. A question of greater concern to
      persons using the two-stage model of carcinogenesis is under what conditions can
      identifiable parameters be obtained from the observed experimental data. We
      outline how to obtain identifiable parameters for the two-stage model.

PMID- 9232020
TI  - Some properties of the hazard function of the two-mutation clonal expansion
      model.
AB  - We discuss the hazard function of the two-mutation clonal expansion model with
      time-dependent parameters, with particular emphasis on identifiability of the
      parameters. We explicitly construct identifiable parameter combinations, and
      illustrate the properties of the hazard function under perturbations of the
      underlying biological parameters.

PMID- 9232021
TI  - Heavy metal contamination of settling particles in a retention pond along the A
      71 motorway in Sologne, France.
AB  - A retention pond is a part of a drainage system designed to control water flow
      during rainstorms and to trap contaminated solid particles washed off by runoff
      water from a motorway. A series of studies have been carried out concerning the
      physico-chemical characteristics of the particles which settle down in such a
      pond in order to evaluate the effectiveness of the pond as a trap for heavy
      metals such as Pb, Zn and Cd. The highly contaminated roadside soil and the
      uncontaminated background soil were also studied for comparison. The settling
      particles had heavy metal concentrations 2-8 times higher than the background
      Sologne soil, depending on the metals. Heavy metal concentrations in the roadside
      soil were 7-26 times higher than those in the former. Sequential extractions,
      using the procedure of Tessier et al. (1979) illustrate that the highly
      contaminated roadside soil consisted mainly of the readily soluble fractions for
      all three heavy metals, with a limited proportion of residual metals. In the
      settling particles, the proportion of the latter is significantly increased, up
      to one-third of the total. The high concentration differences between the
      roadside soil and the settling particles indicates that most of the heavy metals
      are lost to the surroundings even before reaching the retention pond. Cadmium
      exhibited a specific behavior in that the most soluble fraction (exchangeable),
      which is negligible for Pb and Zn, occupied as much as one-fourth of the total in
      the roadside soil. Based on the 'enrichment factor' normalized to Fe introduced
      by Helz in 1976, the degree of contamination by heavy metals for the roadside
      soil and the settling particles was evaluated. The level of contamination was
      very severe in the roadside soil, while it was not so great in the settling
      particles. Suggestions are made to improve their removal efficiency.

PMID- 9232022
TI  - A collective model for predicting the long-term behaviour of radionuclides in
      rivers.
AB  - Here I describe a collective model to predict the long term behaviour of 90Sr in
      river catchments. The model is applied to 11 Italian rivers contaminated by 90Sr
      due to nuclear explosions in the atmosphere over past decades. The uncertainty at
      the 68% confidence level of the model, when used as a generic tool for evaluating
      the concentration of the radionuclide in water, is a factor 1.8 around the
      predicted values. The reliability of the model output is due to the mutual
      compensation effects of different phenomena occurring in the catchments that lead
      to 'collective' behaviours which are scantily variable and uncertain despite the
      large range of catchment characteristics. The model is based on the assumption
      that the time behaviour of the 90Sr (Bq s-1) transported by water, following a
      single pulse of radionuclide deposition, is the sum of some exponential
      components. In the present paper the components were supposed characterised by
      the following decay constants: lambda 1 = 2.3 x 10(-7) s-1, lambda 2 = 4.2 x 10(
      9) S-1 and lambda 3 = 4.2 x 10(-10) S-1. The average value of 90Sr transfer
      coefficient from the catchment to the river, that, in the case of a pulse
      deposition, is approximately equal to the ratio between the radionuclide
      concentration in water and the deposition, is estimated to be 0.2 m-1.

PMID- 9232023
TI  - Serum copper in institutionalized elderly subjects: relations with dietary intake
      of energy, specific nutrients and haematological parameters.
AB  - The concentrations of serum copper were determined as an indicator of corporal
      status of Cu and its relation to aging in 93 institutionalized elderly subjects
      (24 men and 69 women) in Granada (Spain). We found that aging does not affect
      serum Cu levels in the two age groups included in the study: Group I < 80 years
      and Group II > or = 80 years. Application of linear regression analysis to the
      serum Cu levels and the intake of energy, fibre, iron and magnesium showed a
      statistically significant negative correlation (P < 0.05) among them in all the
      subjects. However, no correlation was observed when the serum Cu levels were
      related to the intake of zinc or vitamin C. Therefore, at the daily intake levels
      of these two nutrients, they do not interfere in the absorption of copper and
      hence do not affect the corporal status of this element in the elderly. Blood
      erythrocyte and haemoglobin concentrations do not show any significant
      correlation with the serum Cu concentrations (P > 0.05).

PMID- 9232024
TI  - A neurobehavioural study of long-term occupational inorganic lead exposure.
AB  - A group of 38 male workers at a secondary smelter (period of employment 2-35
      years; median 10 years) was divided into two subgroups depending on bone-lead
      concentration, arranged as 19 matched pairs according to age, education and job
      level. The median concentrations for finger-bone lead (Bone-Pb) were 16 vs. 32
      micrograms/g; for current blood-lead (B-Pb), 1.6 vs. 1.8 mumol/1; for
      retrospective peak blood-lead (Peak-Pb), 2.7 vs. 3.0 mumol/1; and for a
      retrospective cumulative blood lead index (CBLI), 143 vs. 233 mumol/l x months.
      Nineteen unexposed male workers from a nearby mechanical plant served as
      controls, using the same matching algorithm. The triplets were examined with a
      standardised neuropsychological test battery, and four questionnaires for self
      rating of symptoms and activity/stress level related to work environment. No sign
      of behavioural deterioration was observed in the exposed groups, either in
      objective cognitive tests or in subjective symptom/mood self-rating scales.
      Despite the limited sample size, the statistical power was sufficient to conclude
      that a concealed lead-associated effect was unlikely. Covariations between
      behavioural measures and lead exposure indices were generally low and non
      significant, as a whole not exceeding a random level. No confounding or effect
      modifying factor was detected that could explain the results as a type II error.
      To conclude, a current B-Pb of 1.8 mumol/l was not associated with adverse
      behavioural effects, and a long-term lead exposure around 2.0 mumol/l for 13
      years (mean values) was not associated with permanent brain dysfunction.

PMID- 9232025
TI  - Streamwater nitrate concentrations in six agricultural catchments in Scotland.
AB  - The concentrations of nitrate-N (NO3-N) in catchment inputs and outputs have been
      compared and contrasted between 6 farm catchments in Scotland, 3 in the West and
      3 in the North-East. Forms of intensive animal farming ranging between beef and
      dairy cattle, sheep and poultry give different sources for potential NO3-N
      leakage from the systems. While stream reaches bordered by intensive cereal
      production give rise to the largest inputs to surface waters, climatic influences
      result in the more-efficient use of fertilizer- and farm waste-N in the West, and
      an enhanced potential for N-loss to waters in the cooler North-East, regardless
      of the N-inputs being considerably lower in the latter region. Although the EC
      Nitrate Directive limit of 11.3 mg NO3-N 1(-1) was not exceeded, peak values
      occurring during summer baseflows and autumn soil rewetting were commonly larger
      than the 'target' maximum concentration of 5.65 mg NO3-N 1-1.

PMID- 9232026
TI  - Analysis of transgene integration sites in transgenic pigs by fluorescence in
      situ hybridization.
AB  - The production of pigs transgenic for human decay accelerating factor (hDAF) as
      potential donors for clinical organ xenotransplantation was reported several
      years ago. For this purpose it is required that high levels of hDAF are expressed
      at relevant sites in transplantable organs. Currently, homozygous lines have been
      produced as well as lines from crosses between heterozygous animals from
      different founder lines, termed 'jigsaw' pigs. The purpose of the 'jigsaw'
      crosses is to combine the desirable hDAF protein expression patterns found in
      different founder lines. Initial selection of the 'jigsaw' pigs is based on the
      inheritance of the hDAF integration sites from both lines. Litters with potential
      homozygous transgenics and 'jigsaw' transgenics were analysed by fluorescence in
      situ hybridization (FISH) and slot blot analysis. Results show that both slot
      blot analysis and FISH are suitable to distinguish between pigs that are
      heterozygous and homozygous fir hDAF. However, FISH has the advantage of
      producing results more rapidly. For the identification of 'jigsaw' pigs FISH
      analysis was required since slot blot analysis lacked the required accuracy. On
      basis of these results, FISH analysis was made part of the routine screening
      programme for hDAF transgenic pigs.

PMID- 9232027
TI  - Comparison of amyloid deposition in two lines of transgenic mouse that model
      familial amyloidotic polyneuropathy, type I.
AB  - We previously produced a transgenic mouse line designated MT-hMet30 by
      introducing the human mutant transthyretin (TTR) gene carrying the mouse
      metallothionein promoter, and showed that the presence of human variant TTR is
      sufficient for amyloid deposition in various tissues of these transgenic mice.
      However, the expression pattern of human mutant transthyretin gene in the mouse
      was different from that in man. To analyse pathologic processes, it is essential
      to establish a transgenic mouse line in which the development and tissue-specific
      expression of the human mutant TTR gene is the same as in man. Thus, we produced
      two additional transgenic mouse lines carrying the human mutant TTR gene
      containing either 0.6 kb (0.6-hMet30) or 6.0 kb (6.0- hMet30) of the upstream
      region. The expression levels of 6.0-hMet 30 gene in the liver and serum were the
      same as in man and about 10 times higher than those of 0.6-hMet30 gene in the
      liver and serum were the same as similar tissues to human patients except for the
      peripheral and autonomic nervous tissues. The amyloid deposition started earlier
      and was more extensive in 6.0-hMet30 than 0.6-hMet30 mice, suggesting that the
      serum levels of human mutant TTR are correlated with the occurrence and degree of
      amyloid deposition, to some extent. Neither amyloid deposition nor degenerative
      changes were observed in the peripheral and autonomic nervous systems despite the
      transgene expression in the choroid plexus of the 6.0-hMet30 mice. In the 6.0
      hMet30 mice, amyloid deposition started at 9 months of age, although the serum
      level of human mutant TTR reached the adult level at 1 month. These results
      suggest that intrinsic environmental factors other than the mutant gene are
      involved in the late-onset deposition of amyloid fibrils. Transgenic mice
      described here should be useful for analysing such factors.

PMID- 9232028
TI  - Recombinant human extracellular superoxide dismutase produced in milk of
      transgenic rabbits.
AB  - Expression of human extracellular superoxide dismutase (EC-SOD), a glycosylated,
      tetrameric metalloprotein, was targeted to the lactating mammary gland of
      transgenic rabbits. Efficient expression of the recombinant whey acidic
      protein/ec-sod gene was achieved and up to 3 mg ml-1 of the enzyme was secreted
      into the milk. Rabbit milk-produced recombinant EC-SOD was primarily found in the
      whey and purified by a two-step chromatographic method. To evaluate the rabbit
      milk-produced human EC-SOD, comparisons with native and Chinese hamster ovary
      cell (CHO)-produced EC-SOD were performed. All proteins were tetrameric and N
      glycosylated. The behaviour on SDS-PAGE and size-exclusion chromatography
      indicated that the masses, and thereby the extent of post-translational
      modification of the proteins was similar. The monosaccharide composition of both
      recombinant EC-SOD variants was analysed and indicated similarities in the
      attached N-glycans on the two proteins. Furthermore, the peptide maps of the
      three EC-SOD variants revealed that all proteins had similar polypeptide
      backbones.

PMID- 9232029
TI  - Expression of the human milk protein beta-casein in transgenic potato plants.
AB  - A 1177 bp cDNA fragment encoding the human milk protein beta-casein was
      introduced into Solanum tuberosum cells under control of the auxin-inducible,
      bidirectional mannopine synthase (mas1',2') promoters using Agrobacterium
      tumefaciens-mediated leaf disc transformation methods. Antibiotic-resistant
      plants were regenerated and transformants selected based on luciferase activity
      carried by the expression vector containing the human beta-casein cDNA. The
      presence of human beta-casein cDNA in the plant genome was detected by PCR and
      DNA hybridization experiments. Human beta-casein mRNA was identified in leaf
      tissues of transgenic plants by RT-PCR analysis. Human beta-casein was identified
      in auxin-induced leaf and tuber tissues of transformed potato plants by
      immunoprecipitation and immunoblot analysis. Human beta-casein produced in
      transgenic plants migrated in polyacrylamide gels as a single band with an
      approximate molecular mass of 30 kDa. Immunoblot experiments identified
      approximately 0.01% of the total soluble protein of transgenic potato leaf tissue
      as beta-casein. The above experiments demonstrate the expression of human milk
      beta-casein as part of an edible food plant. These findings open the way for
      reconstitution of human milk in edible plants for replacement of bovine milk in
      baby foods for general improvement of infant nutrition, and for prevention of
      gastric and intestinal diseases in children.

PMID- 9232030
TI  - Influence of the medium composition and plasmid combination on the growth of
      recombinant Escherichia coli JM109 and on the production of the fusion protein
      EcoRI::SPA.
AB  - Plasmid-free and plasmid-harbouring E. coli JM109 strains were investigated in
      shaken flasks, stirred tanks in batch and continuous operation. The shaken flask
      cultivations were performed in M9 minimal medium and in media with various
      protein supplements. The host hardly grows on M9 minimal medium as opposed to the
      plasmid-harbouring cells, which grow well on this medium. All of the investigated
      cells propagate well on protein-containing media. The influence of the
      combinations of repressor plasmid pRK248cI, the protection plasmid EcoR4 and the
      production plasmid pMTC48 were determined on the initial specific growth rate of
      the E. coli JM109 without gene expression, on the yield coefficient of cell
      growth, acetate concentration and acetate yield coefficient in the yeast extract
      containing (HM) medium. The influence of various media on the induction of the
      gene expression were evaluated. In cultivation media with protein supplement, the
      growth rate and yield coefficient increased. The variation of the volumetric and
      specific beta-lactamase activities with the cultivation time were determined in a
      stirred tank reactor in HM medium. With increasing dilution rate the process
      performance decreased. Simple relationships exist between the substrate uptake
      rate and the specific growth rate of the continuous cultivated cells in M9 and HM
      media. The influence of the dilution rate on the cell mass concentration, colony
      forming units, acetate formation, yield coefficients of growth and acetate
      formation, substrate uptake rate, CO2 production rate, ammonium formation rate
      and beta-lactamase activity in M9 and HM media were determined as well. Carbon
      balances of the batch and continuous cultivations indicated high carbon
      recoveries. On account of the higher growth rate of plasmid-harbouring cells than
      than of the plasmid-free cells, the behaviour of the investigated plasmid-free
      and plasmid-harbouring E. coli JM109 cells deviates from the published properties
      of other plasmid-free and plasmid-harbouring E. coli cells.

PMID- 9232031
TI  - Towards a molecular level understanding of protein stabilization: the interaction
      between lysozyme and sorbitol.
AB  - The paper is investigating the mechanism of stabilization of proteins by polyols
      at the molecular level. It is addressing the interactions of sorbitol, a polyol
      commonly used as a protein stabilizing agent, with hen egg white lysozyme, a well
      studied protein. Differential scanning calorimetry shows an increase in
      denaturation temperature of lysozyme upon addition of sorbitol at a concentration
      of 250 mM and above. Increasing sorbitol concentration also caused an increase in
      signal intensity of the CD spectrum of lysozyme in the wavelength region of 280
      300 nm. Two-dimensional nuclear magnetic resonance spectroscopy was used to
      examine interactions between lysozyme and sorbitol. Most significant changes are
      manifest in the anomalous relaxation properties of Ala and Thr methyl groups
      indicating modifications of local motions and possibly compression of the entire
      structure. This is further corroborated by new intra-protein nuclear Overhauser
      effects in the presence of sorbitol. There is also evidence that water is
      displaced from the enzyme surface close to Ile-88 upon addition of sorbitol. In
      combination these results reveal a complex interplay of different interactions.
      Comparison to NMR-spectra of lysozyme with a bound inhibitor (tri-N-acetyl
      glucosamine) shows that the interaction with sorbitol affects spatially disparate
      regions of the protein.

PMID- 9232032
TI  - Secretion of authentic 20-kDa human growth hormone (20K hGH) in Escherichia coli
      and properties of the purified product.
AB  - Using Bacillus amyloliquefaciens neutral protease gene (npr), we have constructed
      a secretion system of 20-kDA human growth hormone (20K hGH) in E. coli. The
      secretion-signal region from npr was modified inserting a fragment coding a 2Lys
      5Leu cluster. In this system we found that co-expression of glutathione reductase
      remarkably increased accumulation level of 20K hGH in periplasm and confirmed
      that secreted 20K hGH was correctly processed. The recombinant 20K hGH was highly
      purified and subjected to analyses of physicochemical properties and biological
      activities which are still unclear and controversial due to difficulty in
      preparing the sample with authentic structure. The secreted recombinant product
      had authentic disulfide linkages and showed molecular weight of 20,270.5 +/- 3.7
      (theoretical value, 20,269.9). The results suggest that the recombinant 20K hGH
      is a full agonist on rat growth promotion and lipolysis stimulation in isolated
      rat adipose tissues. In particular, the lipolysis-stimulating activity of 20K hGH
      was distinct as compared with that of 22K hGH under physiological concentration.
      Cell proliferation activity via prolactin-receptor in Nb-2 lymphoma was obviously
      low as compared with that of 22K hGH.

PMID- 9232033
TI  - Biosorption of lead and zinc from solutions using Streptoverticillium cinnamoneum
      waste biomass.
AB  - Mycelial wastes of microbial origin from fermentation industries have been
      recognized as potential biosorbents for decontamination of waste waters
      containing heavy metals. Dried, nonliving, granulated biomass of
      Streptoverticillium cinnamoneum was used for the recovery of lead and zinc from
      solutions. It was found that pretreatment of the biomass with boiling water for
      15 min increased the biosorption of lead and zinc by 52 and 41%, respectively.
      The optimum pH range for lead uptake was 3.5-4.5 while for zinc it was 5.0-6.0.
      The lead and zinc adsorption data when applied to Freundlich and Langmuir
      isotherm equations showed good correlation (r2 = 0.97) and hence equal conformity
      to both models. The Scatchard plots indicated clearly that more than one type of
      binding sites were involved in the adsorption of lead and zinc by the biomass.
      The maximum loading capacity of S. cinnamoneum biomass was found to be 57.7 mg/g
      for lead and 21.3 mg/g for zinc with boiling water pretreatment. The loaded
      metals could be desorbed effectively with dilute hydrochloric acid, nitric acid
      and 0.1 M EDTA. Treatment with 0.1 M sodium carbonate permitted reuse of the
      desorbed biomass although the metal loading capacity in the subsequent cycles
      decreased by 14-37%. The metal biosorbent granules prepared are a value-added
      product that has the potential for removal/recovery of lead and zinc from dilute
      solutions on a commercial scale.

PMID- 9232034
TI  - Self-assembling of glutathione S-transferase/calmodulin fusion protein on
      chemically modified gold surface.
AB  - The fusion protein technique was used to prepare an artificial polyfunctional
      protein from calmodulin (CaM) and glutathione S-transferase (GST). The fusion
      protein was designed, expressed, and then assembled to the glutathione self
      assembled gold surface. The protein assembly was confirmed through enzyme binding
      assay and enzyme immunoassay. Specific binding of the fusion protein to
      glutathione self-assembled on the gold surface was assessed via a quartz crystal
      microbalance (QCM). The fusion protein was reversibly adsorbed and desorbed by
      the competitive binding of glutathione present in a solution, thus showing that
      the binding of the fusion protein was specific and had a highly oriented
      molecular configuration.

PMID- 9232035
TI  - Fever revisited.

PMID- 9232036
TI  - Tobacco and children. An economic evaluation of the medical effects of parental
      smoking.
AB  - OBJECTIVE: To determine the economic influence of pediatric disease attributable
      to parental smoking. DATA SOURCES: Computerized bibliographic databases were
      searched. Subject headings included asthma, burn, cost, low birth weight, otitis
      media, respiratory syncytial virus bronchiolitis, sudden infant death syndrome,
      and tobacco smoke pollution. The following constraints were applied to the
      published articles we studied: publication time, January 1980 through May 1996;
      age range of children studied, neonate to 18 years; and written in English.
      Articles used specifically as references for cost issues were limited to studies
      performed in the United States. DATA EXTRACTION: This study is a literature
      synthesis, which uses as its primary source the results of previously published
      best estimates. This is not a meta-analysis of studies analyzing the
      relationships between childhood disease and smoking. RESULTS: Using data for
      relative risk, prevalence, and cost of illness and death, we calculated the
      attributable risk fraction and corresponding direct medical expenditures and
      costs for loss of life. Costs are adjusted to 1993 dollars. Estimated annual
      excess cases of childhood illness and death attributable to parental smoking
      include low birth weight (46,000 cases, 2800 perinatal deaths), sudden infant
      death syndrome (2000 deaths), respiratory syncytial virus bronchiolitis (22,000
      hospitalizations, 1100 deaths), acute otitis media (3.4 million outpatient
      visits), otitis media with effusion (110,000 tympanostomies), asthma (1.8 million
      outpatient visits, 14 deaths), and fire-related injuries (10,000 outpatient
      visits, 590 hospitalizations, and 250 deaths). CONCLUSIONS: Parental smoking is
      an important preventable cause of morbidity and mortality among American
      children; it results in annual direct medical expenditures of $4.6 billion and
      loss of life costs of $8.2 billion. Additional efforts to reduce children's
      exposure to tobacco smoke are warranted.

PMID- 9232037
TI  - Over-the-counter medications. Do parents give what they intend to give?
AB  - OBJECTIVE: To evaluate caregiver (parent or guardian) use of over-the-counter
      medications (OTCs) as related to the accuracy and correctness of dosing for
      children seen at a pediatric emergency department with nonemergent concerns.
      DESIGN: Prospective patient series. SETTING: A tertiary care pediatric emergency
      center. PARTICIPANTS: A representative sample of children with nonemergent chief
      complaints. INTERVENTIONS: A questionnaire about general demographic
      characteristics, recent OTC use, and medical history of the patients was given to
      each caregiver. A mock scenario was then presented that required the caregivers
      to determine and measure a correct dose of acetaminophen for their child. A dose
      of 9 to 16.5 mg/kg was considered correct. Accuracy of measuring was considered
      within +/-20% of the caregivers' stated intended dose for their child. RESULTS:
      One hundred caregivers were enrolled in the study. Mean caregivers' age was 29
      years, with 82% having at least a high school education. Seventy-seven percent of
      their children used OTCs within the previous 2 months, and Tylenol
      (acetaminophen) was the most commonly used. While 66% of the caregivers reported
      Tylenol use, only 8% reported the use of acetaminophen. During the dosing
      scenario, only 40% of the caregivers stated an appropriate dose for their child
      and only 67% accurately measured the amount of acetaminophen they intended. Forty
      three percent measured out a correct amount of acetaminophen for their child.
      However, almost one third of these occurred strictly by accident because they
      inaccurately measured an improper intended dose. Combining these results, only
      30% of the caregivers were able to demonstrate both an accurately measured and
      correct dose for their child. CONCLUSIONS: Although a large number of caregivers
      administer OTCs, knowledge of these medications, and accuracy and correctness of
      dosing remain a marked concern. Improved caregiver education on the accuracy and
      correctness of dosing OTCs is necessary.

PMID- 9232038
TI  - A national survey to understand why physicians defer childhood immunizations.
AB  - OBJECTIVE: To determine the causes of low childhood immunization rates based on
      physicians' knowledge, attitudes, and self-reported practices concerning
      childhood immunization. DESIGN: A standardized telephone survey conducted by
      trained interviewers. SETTING: Primary care physicians across the United States.
      PARTICIPANTS: A stratified random sample of office-based family physicians,
      pediatricians, and general practitioners younger than 65 years was selected from
      the American Medical Association master file list that includes nonmembers.
      Physicians seeing 5 or more patients per week younger than 6 years and having 50%
      or more primary care patients were eligible for study. Of 1769 eligible
      physicians who spoke directly with the interviewers, 70% (N = 1241) completed the
      questionnaire. INTERVENTIONS: The interview was designed to determine physicians'
      likelihood of recommending vaccination in common clinical scenarios and to probe
      reasons behind these decisions. RESULTS: Only 4% of physicians who thought the
      risk for side effects was increased by upper respiratory tract infection (URI)
      were likely to vaccinate a child with URI vs 55% of physicians who thought there
      would be no increased risk (P < .001). Eighty-three percent of those who thought
      the efficacy of measles, mumps, and rubella vaccine would not be affected by a
      URI recommended vaccination vs only 8% of physicians who thought efficacy would
      decrease (P < .001). Some respondents (11%) would not administer 3 injectable
      vaccines simultaneously based on beliefs about side effects, parental objections,
      and vaccine efficacy. Physicians' likelihood of vaccination also varied by type
      of visit: 47% were less likely to vaccinate a child with a URI in an acute care
      as opposed to a well-child setting. CONCLUSION: Physicians' beliefs and practice
      policies materially influence their likelihood of recommending vaccinations.

PMID- 9232039
TI  - Low birth weight and Latino ethnicity. Examining the epidemiologic paradox.
AB  - OBJECTIVE: To assess the relation between Latino ethnicity, Latino subgroup, and
      low birth weight (LBW). DATA SOURCES: From the MEDLINE computer data-base, we
      used the key words birth weight; infant, LBW; Latinos; Hispanic Americans; Cuban
      Americans; Mexican Americans; and Puerto Ricans to identify studies that analyzed
      LBW in Latinos. STUDY SELECTION: Thirty-two studies, published from 1982 to 1996,
      that analyzed US Latinos and whites or multiple Latino subgroups, that used the
      revised definition of LBW (< 2500 g), and had a large sample size (> 10,000) were
      selected. DATA EXTRACTION: Two reviewers extracted LBW rates and data on the
      relation between Institute of Medicine risk factors and LBW by maternal ethnicity
      and Latino subgroup. DATA SYNTHESIS: Low-birth-weight rates were similar for
      Latino (median, 6.2%) and white infants (median, 5.8%). By Latino subgroup, LBW
      rates were similar for Central/South American, Cuban, Mexican, and white infants.
      Puerto Rican infants had consistently higher LBW rates (median, 9.1%). Two risk
      factors-maternal birth-place and gestational weight gain-were identified as
      confounders of the relation between Latino ethnicity, Latino subgroup, and LBW.
      CONCLUSIONS: Low-birth-weight rates of Latinos and whites are similar, consistent
      with the "epidemiologic paradox" of unexpectedly favorable perinatal outcomes for
      Latinos. However, this paradoxical relation for all Latinos masks the notably
      elevated LBW risk among Puerto Ricans. Further study of LBW among Latinos,
      including cultural factors, is needed.

PMID- 9232040
TI  - Efficacy of Auralgan for treating ear pain in children with acute otitis media.
AB  - OBJECTIVE: To determine the efficacy of Auralgan otic solution (combination
      product of antipyrine, benzocaine, and glycerin) compared with an olive oil
      placebo in the management of moderate to severe ear pain in children with acute
      otitis media (AOM). DESIGN: Children 5 years or older who presented with ear pain
      and eardrum findings indicative of AOM were randomly assigned to treatment with
      Auralgan or olive oil drops instilled into the external auditory canal(s) of the
      affected ear(s). All children were also treated with 15 mg/kg of acetaminophen in
      a single dose. Ear pain was assessed by means of 2 visual analog seales-a linear
      scale and a color scale-at study entry and 10, 20, and 30 minutes later (T0, T10,
      T20, and T30, respectively). Results of the measurements on the 2 scales were
      evaluated independently and were averaged to determine an ear pain score. A
      baseline ear pain score of at least 3 points was required for study entry. Four
      outcome measures regarding ear pain score at T10, T20, and T30 were used: (1)
      proportion of subjects who showed 50% reduction, (2) proportion of subjects who
      showed 25% reduction, (3) proportion of subjects who showed a 1 or more point
      reduction, and (4) mean score over time. SETTING: Primary care center and
      emergency department of a children's hospital. PARTICIPANTS: Fifty-four children
      aged 5 to 19 years with ear pain and AOM. RESULTS: The Auralgan and placebo
      groups were comparable regarding age, sex, race, laterality of AOM, and T0 ear
      pain score. By each of the 4 measures used, the response to treatment
      consistently favored the Auralgan group, but only at T30 were any differences
      statistically significant. CONCLUSION: In children with AOM-associated ear pain
      who are treated with acetaminophen, topically applied Auralgan appears likely to
      provide additional relief in varying degree within 30 minutes.

PMID- 9232041
TI  - The impact on families of pediatric resident departure from a continuity clinic
      practice.
AB  - OBJECTIVE: To determine views of parents whose children were reassigned to new
      resident pediatricians at a continuity clinic because their previous
      pediatricians had completed residency. DESIGN: Cross-sectional survey. SETTING:
      Hospital-based resident continuity clinic. PARTICIPANTS: Ninety parents whose
      pediatricians were graduating were interviewed from June through August 1995.
      RESULTS: Most parents felt they knew their resident pediatrician well and that
      the resident knew their child well. Sixty-eight parents (76%) were sad about the
      transition, 33 (37%) were angry, 30 (33%) felt abandoned, and 6 (7%) were
      relieved. Three fourths of the parents thought it was very important for the
      family to be involved in the reassignment process, yet less than one fifth had
      been asked their opinion. Half of the families were experiencing their second or
      greater transition. Families undergoing their first, vs second or greater
      transitions, were more likely to feel they knew the resident well (P = .01), and
      that the resident knew their child well (P = .04). Despite the transitions, 86
      (96%) of families stated they would continue to have their child receive medical
      care at the current site because they knew their child would receive good care.
      CONCLUSIONS: Strong physician-patient-parent relationships develop when residents
      are the pediatric primary care providers. Parents want to be informed regarding
      transitions. Pediatricians need to be sensitive to the impact of transitions and
      to negotiate with families in choosing their future pediatrician. These results
      have implications for other practice sites where physician turnover occurs.

PMID- 9232042
TI  - One-year experience with an inpatient asthma clinical pathway.
AB  - OBJECTIVE: To study the effects of an inpatient asthma clinical pathway on the
      processes and outcomes for children who were admitted to a hospital for the
      treatment of asthma. DESIGN: Before-and-after study. SETTING: A private nonprofit
      academic children's hospital in Seattle, Wash. PATIENTS AND METHODS: Three
      hundred forty-two admissions of 297 patients in the first year of the asthma
      clinical pathway were compared with 353 admissions of 292 similar patients in the
      previous year. Patients who required intensive care, were younger than 2 years,
      or had a major chronic disease were excluded. INTERVENTION: Asthma was chosen for
      the development of a clinical pathway because of its large number of admissions,
      involvement of multiple health care providers (nurses, physicians, and
      respiratory therapists), predictable hospital course, and variable lengths of
      hospital stay. The pathway was a consensus-based guideline for patient management
      that was intended to be adapted to the care of an individual patient. Prior to
      the implementation of the clinical pathway, nurses, attending physicians, house
      staff, and respiratory therapists were trained in its use. The main hospital
      chart of each patient who was admitted to the pathway had a flowchart that
      outlined day-to-day guidelines for monitoring and care. Nursing staff were
      responsible for documenting when a patient's care varied from the pathway, and
      these variances were entered into a computer database. OUTCOME MEASURES: Use of
      peak flowmeters, steroids, laboratory studies, radiological studies, and
      respiratory therapy was assessed by analyzing the patients' electronic billing
      records. For patients enrolled in the pathway, additional data on process of care
      were obtained by analyzing the variance database. For both groups, the total
      charges, length of stay, and rate of readmission to the hospital were measured by
      use of the billing records. RESULTS: There were no significant differences in the
      use of steroids or peak flowmeters, average lengths of stay, or total charges
      between the 2 groups. However, patients in the "pathway group" had significantly
      lower average charges for laboratory ($26 vs $39; P < .05) and radiology ($32 vs
      $55; P < .001) services. Variances from the pathway guidelines were most often
      related to the patients' responses to therapy. CONCLUSIONS: The asthma clinical
      pathway had no effect on clinical outcomes and small effects on the use of
      resources. Further development, including physician and nurse training, computer
      and administrative support, and clinical severity scales, are needed to develop
      the potential utility of the clinical pathway as a research and quality assurance
      tool.

PMID- 9232043
TI  - Are immunizations an incentive for well-child visits?
AB  - OBJECTIVE: To assess the beliefs of parents and the visit patterns of their
      children to determine whether immunizations act as an incentive to use well-child
      care. DESIGN AND METHODS: Medical record audits provided data on immunizations
      and well-child visits. Two questions from a parent interview were used to
      identify 4 groups of parents: (1) motivated and (2) unmotivated to keep a well
      child care appointment regardless of whether immunizations are scheduled, (3)
      vaccine-motivated and (4) checkup-motivated (parents who were influenced
      negatively by the prospect of receiving vaccinations). The percentage of children
      with a visit at each age window for well-child visits and the percentage up-to
      date for their immunizations at given ages were compared across the 4 groups. The
      4 groups were also compared for other parental attitudes about immunizations and
      well-child visits, and on sociodemographic and access characteristics. RESULTS:
      Most (73.3%) of the 502 parents surveyed were classified as motivated and 5% as
      unmotivated to keep a well-child care appointment regardless of whether an
      immunization was scheduled. Only 18.3% were categorized as vaccine-motivated and
      3.4% as checkup-motivated. For all 4 groups, there was no discernible difference
      in attendance between immunization and nonimmunization visits. Attendance in the
      windows for well-child visits and percentage of children up-to-date on
      immunizations declined with increasing age. CONCLUSIONS: In this inner-city
      population, attendance patterns at visits did not support the incentive
      hypothesis. This finding should reassure clinicians that providing immunizations
      outside of regular well-child care visits will not necessarily decrease
      attendance at visits for well-child care.

PMID- 9232044
TI  - Mechanisms of pediatric electrical injury. New implications for product safety
      and injury prevention.
AB  - OBJECTIVES: To determine age-specific mechanisms of electrical injury in
      children, to examine product safety regulation of the major sources of electrical
      injury hazard, and to assess the adequacy of current prevention strategies.
      DESIGN: Case series of 144 pediatric and adolescent electrical injuries in
      patients seen in the specialized burn center and tertiary care hospital between
      1970 and 1995, examination of Consumer Product Safety Commission product recall
      reports for electrical injury hazards between 1973 and 1995, and review of the
      National Electric Code. RESULTS: Eighty-six cases of electrical injuries resulted
      from low-voltage (< 1000-V) exposures, all occurring within the home. In children
      aged 12 years and younger, household appliance electrical cords and extension
      cords caused more than 64 (63%) of 102 injuries, whereas wall outlets were
      responsible for only 14 (15%) of injuries. Fifty-eight cases resulted from high
      voltage exposures, accounting for 38 (90%) of 42 injuries in children older than
      12 years. No federal safety regulations for electrical cords exist, although
      voluntary standards have been adopted by many manufacturers. Among 383 consumer
      products identified by the Consumer Product Safety Commission to be electrical
      injury hazards, 119 were appliance cords, extension cords, or holiday stringed
      light sets. Several products numbered more than 1.5 million units in US household
      distribution prior to the investigation by the Consumer Product Safety
      Commission. CONCLUSIONS: Household electrical cords are the major electrocution
      hazard for children younger than 12 years, yet no federal safety mandates exist.
      Despite voluntary standards, noncompliant manufacturers can introduce vast
      numbers of unsafe cords onto the US household market every year. Conversion of
      existing voluntary safety guidelines into federally legislated standards may be
      the most effective intervention against pediatric electrocutions.

PMID- 9232045
TI  - A randomized controlled trial of penicillin vs clindamycin for the treatment of
      aspiration pneumonia in children.
AB  - OBJECTIVE: To compare the effectiveness of intravenous penicillin vs clindamycin
      for the treatment of aspiration pneumonia. DESIGN: A double-blind, randomized
      controlled trial. SETTING: A tertiary care pediatric hospital. PATIENTS: We
      enrolled 42 children, aged 6 months to 18 years, who were admitted to the
      hospital for the treatment of aspiration pneumonia. All of the children had
      underlying conditions that predispose to aspiration. INTERVENTION: The patients
      were randomly assigned to receive intravenous penicillin G sodium, 250,000 U/kg
      every 24 hours, or intravenous clindamycin phosphate, 30 mg/kg every 24 hours.
      MAIN OUTCOME MEASURE: The primary outcome measure was "time to ready for
      discharge" from the hospital. RESULTS: In an effectiveness (intention to treat)
      analysis, the median time (interquartile range) to ready for discharge from the
      hospital was 4.9 days (range, 2.8-6.5 days) in the penicillin-treated group and
      3.4 days (range, 2.3-6.8 days) in the clindamycin-treated group (P = .66).
      Results were not markedly altered when adjusted for the age difference of the
      groups or in the efficacy analysis (after the exclusion of 9 patients who
      withdrew from the trial). Rates for readmission to the hospital were similar in
      the 2 groups. CONCLUSION: Penicillin and clindamycin seem to be equally effective
      for the treatment of aspiration pneumonia in children hospitalized for this
      illness.

PMID- 9232046
TI  - The father's role during infancy. Factors that influence maternal expectations.
AB  - OBJECTIVE: To describe factors that influence maternal expectations of the
      father's role during infancy. RESEARCH DESIGN: Cross-sectional survey. SETTING:
      Postpartum obstetric ward of an inner-city teaching hospital. SUBJECTS: Mothers
      who were residents in the inner-city communities that surround the hospital and
      who were recently delivered of a newborn. SELECTION PROCEDURE: Consecutive
      sampling from March to May 1992. MEASUREMENTS: Through structured maternal
      interviews, the father's expected role was measured in terms of accessibility,
      engagement in child care tasks, and decision-making responsibility. Influences
      included demographics, the mother's desire for the father's involvement, and her
      perceptions of his motivation, prenatal support, and ability to parent. RESULTS:
      Of 226 eligible mothers, 197 (87%) were interviewed. Expectations varied widely.
      Concerning accessibility, 48% and 18% of the mothers expected to see the father
      daily and less than weekly, respectively. Concerning engagement, 81% of the
      mothers expected some paternal involvement; the average mother assumed that the
      father would participate in one third of child care tasks. Concerning decision
      making responsibility, 34% of the mothers expected to share all decisions; 30%
      expected to share none. In all areas, expectations were positively associated
      with the mother's desires, the strength of the parents' relationship, and the
      mother's perceptions of the father's motivation and ability to parent and the
      father's prenatal involvement (all, P < .001). Expected accessibility and
      engagement were greater for fathers who worked; expected engagement and decision
      making responsibility were greater for fathers without children from other
      relationships (all, P < .03). CONCLUSIONS: The maternal desire for the father's
      participation, the strength of the parents' relationship, the mother's perception
      of the father as a parent, and the father's prenatal involvement are all
      consistently associated with the maternal expectations of the father's role. The
      demographic characteristics of either parent are not as strongly or consistently
      associated with the maternal expectations.

PMID- 9232047
TI  - Preferences of pregnant women and physicians for 2 strategies for prevention of
      early-onset group B streptococcal sepsis in neonates.
AB  - OBJECTIVES: To assess preferences of pregnant women, pediatricians, and
      obstetricians for the policies of the American College of Obstetrics and
      Gynecology (ACOG) and American Academy of Pediatrics (AAP) for reducing the
      incidence of neonatal group B streptococcal (GBS) sepsis. DESIGN: An interactive
      interview using a computer-based decision-making model (analytic hierarchy
      process) and a self-administered survey assessing the interview process. SETTING:
      An obstetric clinic at a university center and offices of practicing physicians
      from the Birmingham, Ala, area. PARTICIPANTS: Ninety-two pregnant women selected
      by a systematic sampling technique and 40 pediatricians and 40 obstetricians
      selected randomly. MAIN OUTCOME MEASURE: Ranking of the ACOG and AAP policies and
      the 5 criteria on which the decision was based: risk of infection to an infant,
      knowledge of maternal GBS status, risk of anaphylaxis to mother, diagnostic tests
      received by healthy infants, and cost. Satisfaction with the interview process
      also was measured. RESULTS: Eighty-three women (90%), 40 pediatricians, and 40
      obstetricians (100%) provided responses suitable for analysis. Sixty-seven
      pregnant women (81%), 26 pediatricians (65%), and 6 obstetricians (15%) preferred
      the AAP strategy. The ACOG policy was the preferred strategy by 34 (85%)
      obstetricians. The 3 groups ranked risk of infection in an infant as the most
      important criterion in their decisions. Ranks for the other criteria differed
      among the 3 groups. Women ranked knowledge of maternal GBS status more important
      than did pediatricians and obstetricians. Thirty obstetricians (75%), 35
      pediatricians (87.5%), and 72 pregnant women (86.7%) liked the interview. Seventy
      three women (88%), 29 pediatricians (72.5%), and 17 obstetricians (42.5%) thought
      physicians should use this type of interview to assist in managing patients.
      CONCLUSIONS: Pregnant women, pediatricians, and obstetricians had different
      priorities when making a decision about GBS policies. These differences led
      obstetricians to prefer a different policy than that of pediatricians and
      pregnant women. Obstetricians were less likely to endorse the use of this
      decision-making technique in their practice than were patients and pediatricians.

PMID- 9232048
TI  - Costs of poison-related hospitalizations at an urban teaching hospital for
      children.
AB  - BACKGROUND: Childhood poisonings continue to exact a notable toll in injury
      related morbidity and economic cost. Because a substantial portion of this
      morbidity and economic cost is associated with hospitalization, an analysis of
      the cost of poisoning hospitalizations might help to identify areas in which
      medical care could be improved and costs could be reduced. OBJECTIVE: To assess
      the aggregate cost of poison-related hospitalizations and to analyze the trends
      in categorical poisoning costs during a 4-year period. DESIGN: Cost-benefit
      analysis of charge data and length of stay (LOS) for poison-related
      hospitalizations. SETTING: Admissions to one urban children's hospital. PATIENTS:
      Case mix data were reviewed to identify those children whose hospitalizations had
      a primary discharge diagnosis related to poisoning in fiscal years 1992 to 1995.
      MAIN OUTCOME MEASURES: Mean aggregate hospital charges and LOS for poisonings
      were compared for each of the 4 years of the study. Comparisons were also made
      with charges and LOS for hospitalizations for all other diagnoses during the same
      period. Trends in hospital charges and LOS for the most common specific types of
      poisoning were analyzed individually. Linear regression statistics were used to
      compare the costs and LOS of specific types of poisoning. RESULTS: There were 638
      poison-related hospitalizations during the 4-year study (0.9% of all pediatric
      hospital admissions). Charges per case decreased from $7934 in fiscal year 1992
      to $4968 in fiscal year 1995 (z = -2.74, P = .006); mean LOS decreased from 5.85
      days in 1992 to 3.45 days in 1995 (z = 2.84, P = .005). These trends exceeded
      smaller trends toward decreasing charges and LOS seen also for non-poison-related
      hospitalizations. Acetaminophen, lead, and antidepressant medications were the
      most common and most costly specific agents implicated in poison-related
      hospitalizations during the study period. Linear regression analysis showed a
      significant decrease in charges (F = 6.35, R2 = 0.09, P = .014) and LOS for
      acetaminophen (F = 4.30, R2 = 0.063, P < .04) but not for lead or antidepressant
      poison-related hospitalizations. CONCLUSIONS: Despite an increasing number of
      children hospitalized for poisoning at one institution during a 4-year period,
      per case hospital charges decreased substantially. The cost savings were
      associated with a marked decrease in LOS. Still, poison-related admissions to a
      single pediatric facility accounted for almost $1 million in hospital charges in
      fiscal year 1995. A few agents are overrepresented; new poisoning prevention
      measures aimed at these toxic agents are warranted. We conclude that further
      outcomes studies are needed to delineate cost-effective improvements in patient
      care targeted toward poisonings owing to those agents.

PMID- 9232049
TI  - Hospital infant formula discharge packages. Do they affect the duration of breast
      feeding?
AB  - OBJECTIVE: To determine whether the duration of breast-feeding is affected by the
      contents of the hospital discharge package. DESIGN: A randomized clinical trial
      with 2 experimental interventions (a discharge package containing a manual breast
      pump only and a discharge package containing a commercially prepared infant
      formula and a manual breast pump) and a control group who received a commercially
      prepared infant formula discharge package only. Sociodemographic characteristics
      and information concerning prior births (including feeding methods) were obtained
      from each mother within 48 hours of her infant's birth. Sources of influence on
      the mother's feeding decision, maternal attitudes concerning breast-feeding, and
      maternal feeding preferences were also assessed. PARTICIPANTS: The sample
      consisted of 763 women who had given birth who were admitted to the maternal
      fetal unit of a midwestern community hospital. MAIN OUTCOME MEASURES: Information
      concerning current method of infant feeding was obtained from telephone
      interviews conducted at 2-week intervals until the infant was 16 weeks old. The
      data were analyzed using descriptive statistics, multivariate analysis of
      variance, logistic regression analysis, and survival analysis. RESULTS: The
      content of the hospital discharge package did not affect whether the mother
      engaged in exclusive or partial breast-feeding during the 16-week follow-up
      interval. However, there was some evidence that providing formula samples at
      discharge from the hospital increased the duration of exclusive breast-feeding
      compared with providing a manual breast pump. CONCLUSION: This study does not
      support the assumption that inclusion of infant formula in hospital discharge
      packages decreases the duration of breast-feeding.

PMID- 9232051
TI  - Radiological case of the month. Pulmonary aplasia.

PMID- 9232050
TI  - Teaching residents to teach. An instructional program for training pediatric
      residents to precept third-year medical students in the ambulatory clinic.
AB  - OBJECTIVE: To provide second- and third-year pediatric residents with practical
      teaching skills for precepting third-year medical students in the outpatient
      clinic. DESIGN: Educational intervention with 3-month follow-up of participants.
      SETTING: University teaching hospital. PARTICIPANTS: Second- and third-year
      pediatric residents. INTERVENTION: A curriculum for a half-day workshop to
      provide residents with 6 key clinical teaching skills. Residents participated in
      the workshop and then were observed by trained faculty as they precepted third
      year medical students in the pediatric clinic. MAIN OUTCOME MEASURE: Direct
      observation of resident-student precepting encounters, noting the presence or
      absence of their use of clinical teaching skills taught in the workshop. RESULTS:
      Twenty-one of 23 pediatric residents participated in the workshop. Observation of
      56 resident teaching encounters before and after the workshop showed that the
      residents improved their clinical teaching skills. Residents valued the workshop,
      and many suggested it should also be considered for faculty development.
      CONCLUSIONS: Residents can be taught clinical teaching skills in a half-day
      workshop. These skills also are applicable in various clinical venues. With the
      increasing interest in using community-based primary care physicians for student
      and resident education, this curriculum is well suited for training practicing
      clinicians to teach in their own practice sites.

PMID- 9232052
TI  - Picture of the month. Facial nerve palsy secondary to Epstein-Barr virus
      infection.

PMID- 9232053
TI  - Pathological case of the month. Ectodermal dysplasia.

PMID- 9232054
TI  - Pathological case of the month. Arrhythmogenic right ventricular dysplasia.

PMID- 9232055
TI  - Velocardiofacial syndrome presenting as hypocalcemia in early adolescence.

PMID- 9232056
TI  - The diagnostic value of the respiratory rate in febrile children younger than 2
      years.

PMID- 9232057
TI  - [Morbid associations in Crohn's disease. Study of a series of 832 patients].
AB  - OBJECTIVES: Depending its frequency, the association in the same subject of
      Crohn's disease and another pathology can be fortuitous or the expression of
      genetic or environmental interrelationships. The aim of our study was to identify
      among a series of patients with Crohn's disease preliminary data which would be
      suggestive of a significant association between Crohn's disease and other
      pathologies. PATIENTS AND METHODS: Personal and familial histories were collected
      in 832 patients with Crohn's disease who were seen consecutively in the same
      hospital clinic from 1974 to 1994. RESULTS: We found 4 cases (0.5%) of associated
      Crohn's disease-multiple sclerosis and Crohn's disease-rheumatoid purpura in the
      same patient. Each of the following genetic diseases was associated with Crohn's
      disease in one patient (0.1%): Charcot-Marie-Tooth disease, deuteroanopia,
      multiple exostosis, familial ichthyosis, periodic disease. CONCLUSION: We
      describe for the first time sporadic cases of associated Crohn's disease and
      another rare disease, Charcot-Marie-Tooth disease, familial ichthyosis and
      periodic disease. We suggest that there is a significant interrelationship
      between personal and familial histories of Crohn's disease and multiple sclerosis
      which should be verified in prospective studies.

PMID- 9232059
TI  - [Struma ovarii or malignant ovarian goiter. A case].
AB  - BACKGROUND: We report a case of follicular struma ovarii observed in an ovary
      teratoma without metastatic dissemination. CASE REPORT: A right ovarian tumor was
      discovered at ultrasound examination in a 31-year-old woman complaining of low
      abdominal pain. The patient underwent laparoscopic exploration and a 4-cm cystic
      mass of the right ovary was removed. Microscopic examination showed a malignant
      struma ovarii of the follicular type with vascular space invasion; other
      teratomous elements were identified. Immunohistochemical staining for
      thyroglobulin confirmed the nature of the tumor. The patient was treated by
      complete right ovariectomy followed by total thyroidectomy and administration of
      radioactive iodine (99 mCi I-131). Repeat I-131 body scan performed at 6 months
      was normal. DISCUSSION: Struma ovarii is a rare type of ovarian teratoma,
      consisting mainly of thyroid tissue. The incidence of malignant struma ovarii is
      below 1% and fewer than two dozen cases with distant metastases have been
      reported. The major problem associated with struma ovarii has been the
      establishment of criteria for malignancy.

PMID- 9232058
TI  - [Polyclonal lymphocytosis with binucleated lymphocytes. Morphological,
      immunological, cytogenetic and molecular analysis in 15 cases].
AB  - OBJECTIVES: Describe the clinical, immunological, cytogenetic and molecular
      aspects of polyclonal lymphocytosis with binucleated peripheral lymphocytes in
      order to ascertain the therapeutic consequences. PATIENTS AND METHODS: Fifteen
      patients, 13 women, 2 men, with a total lymphocyte count persistently above 4 x
      10(9)/l at successive counts and binucleated lymphocytes on blood smears were
      studied. RESULTS: The syndrome is easily recognized at careful examination of
      blood smears which show binucleated lymphocytes and lymphoid cells with
      heterogeneous morphology. The lymphocytosis is polyclonal. The clinical situation
      remains stable without treatment despite cytogenetic clonality which contrasts
      with molecular polyclonality. DISCUSSION: Polyclonal lymphocytosis with
      binucleated lymphocytes is a clinical entity characterized by 1) nearly exclusive
      female predominance, mainly in young smokers; 2) lymphocyte counts above 4 x
      10(9)/l which persist (> 6 months), are unchanged over time and fortuitously
      discovered; 3) lymphocytosis with binucleated lymphocytes on blood smears; 4)
      polyclonal lymphocytosis; 5) increased polyclonal serum IgM; and 6) recurrent
      cytogenetic anomalies with an isochromosome supenumerary marker, e.g. +i (3q).
      The etiology remains unknown: the role of smoking genetic predisposition or viral
      factors remains to be determined.

PMID- 9232060
TI  - [Sister Mary Joseph's nodule].

PMID- 9232061
TI  - [Pulmonary complications disclosing polymyositis. 2 new cases].

PMID- 9232062
TI  - [Hospital follow-up of patients with HIV infection: towards new modalities of
      management].

PMID- 9232063
TI  - [Combined kidney-pancreas transplantation: what are the costs and benefits, who
      are the recipients?].
AB  - As the requirement for immunosuppressive therapy after pancreas transplantation
      for insulin-dependent diabetes, which has compromised its use in non-uremic
      patients, cannot be avoided in uremic patients undergoing kidney transplantation,
      the benefits of combined kidney-pancreas transplantation might be sufficient to
      counterbalance the risks of the procedure. The International Pancreas Transplant
      Registry has collected data on over 7000 combined transplantations, allowing
      evaluation of the risks involved, assessment of patient benefit and
      identification of indications. Compared with renal graft alone, survival after
      combined transplantation is equivalent in patients under 45 years of age, but
      decrease in older patients and those with a history of heart failure. Actuarial
      survival of the pancreas graft, defined as absence of insulinotherapy, is
      currently 78% at 1 year and 65% at 5 years. Although combined transplantation may
      not reach early expectations regarding its affect on the progression of diasets
      complications patients quality of life is greatly improved after successful
      grafting as the daily constraints of regular meals, insulin injections and
      glycemia controls disappear at the same time as the burden of dialysis treatment.
      Combining a pancreas graft with a kidney graft inevitably increases morbidity
      during the post-operative months, but experience has shown that many young
      patients are very willing to pay the price in order to benefit from a combined
      graft. We currently propose combined transplantation in patients under 45 who are
      free of severe cardiovascular disease and accept to reconsider candidates after
      myocardial revascularization. The recent introduction of new immunosuppressive
      drugs such as tacrolimus and mycophenolate offer hope for further improvement in
      success rates. Despite currently disappointing clinical results, pancreatic islet
      cell transplantation provides excitivy perspectives.

PMID- 9232064
TI  - [Homocysteine in case of coronary disease].

PMID- 9232066
TI  - [Analgesics in pediatrics. Before prescribing: recognize and evaluate pain,
      reassure].
AB  - CAREFUL ASSESSMENT: In pediatric clinics, it has become habitual to prescribe
      analgesics in all painful situations. Particular attention must be paid to pain
      experienced by the child and obtaining objective evidence allowing valid
      assessment prior to treatment. ACUTE PAIN: Usually clearly expressed by crying
      screams, agitation, retraction and protection of the painful area, signs of acute
      pain are nonspecific and not proportional to its intensity. PROLONGED PAIN:
      Sadness and depression confound the expression of prolonged pain. Diagnosis may
      be difficult; an association between a potentially painful situation, pain
      relieving positions, and retraction behavior is specific. ESTABLISH CONFIDENCE:
      For both the child and his family, an atmosphere of confidence and a clear
      explanation of the lesions and their treatments are essential to break the
      viscious cycle of pain and anxiety. EXAMINING A CHILD WITH PAIN: Patience is the
      essence of examining children, facial mimics, reactions, movements and positions
      all provide essential information. ASSESSING PAIN INTENSITY: Using the visual
      analogue scale, VAS, children over 5 years of age can show where the pain is on a
      drawing of the body. For those under 5, questioning the family and looking for
      specific signs is an essential source of information. The DEGR scale can be used
      to score prolonged pain in children from 2 to 6 or 8 years of age.

PMID- 9232065
TI  - [Parkinson disease: interrogations and solutions].
AB  - A NEURODEGENERATIVE DISEASE: Idiopathic Parkinson's disease is initially due to a
      selective and specific destruction of the pars compacta dopaminergic neurons in
      substantia nigra. Since the inaugural description in 1817 by J. Parkinson,
      therapeutic progress rapidly accelerated mainly due to a better knowledge of the
      neurobiology of the central nervous system dopaminergic pathways. THERAPEUTIC
      GOAL: The question today is not merely to give a short term pharmacological
      benefit but to maintain a long-term effect while avoiding motor complications
      such as fluctuations, dystonias and dyskinesias. This goal can be achieved while
      using low doses of levodopa, dopaminergic agonists and inhibitors of monoamine
      oxydase-B. PERSPECTIVES: Some more improvements are expected through new avenues
      (inhibitors of catechol-O-methyl transferase, thalamic stimulation, fetal
      grafts). The main challenge is represented by compounds potentially antagonizing
      cell death. In any case, the therapeutic approaches have to be guided by good
      quality clinical trials.

PMID- 9232067
TI  - [Analgesics in pediatrics. Drugs for pain relief in children].
AB  - FUNDAMENTAL: Analgesia is a fundamental part of management as it helps avoid the
      morbid effects of pain itself and improves confidence so the child and his
      parents can accept more easily the diagnosis and proposed treatment. The World
      Health Organization has established a classification of analgesics. USE OF
      PLACEBOS: The placebo effect depends on several factors including anxiety,
      confidence, and the patient's- and prescriber's-expectations and convictions). It
      is observed early in the first years of childhood. Use of placebos is not
      recommended as a favorable reaction can be interpreted wrongly, disqualifying the
      complaint. EFFICACY LEVELS: For level 1, paracetamol has little toxicity and is
      easily managed for first line use; aspirin and nonsteroid antiinflammatory drugs
      can also be used if there are no contraindications. Level 2 drugs, codeine or
      dextropropoxyphene (which is not available in a pediatric formulation) are
      required for any manifestation of pain not relieved by level 1 drugs. Level 3
      corresponds to strong central analgesics, mainly morphine. SPECIFIC PAIN:
      Antispasmodic agents in combination with paracetamol give partial relief of
      visceral pain without masking symptoms. Local anesthetics improve comfort without
      compromising safety. Neurogenic pain does not respond to usual analgesics and can
      be relieved with tricyclic antidepressors for burning sensations or antiepileptic
      drugs for fulgurant pain. TREATMENT-RELATED PAIN: Iatrogenic pain, by definition,
      must be systematically anticipated and prevented.

PMID- 9232068
TI  - [Mucus secreting tumor of the appendix (appendiceal mucocele)].

PMID- 9232069
TI  - [A comparative study of 4 diagnostic strategies in coronary artery disease. A
      theoretical approach].

PMID- 9232070
TI  - [A comparative study of 4 diagnostic strategies in coronary artery disease. A
      theoretical approach].
AB  - The prognosis of patients with coronary artery disease is constantly improving
      mainly due to better control of risk factors, to improved methods of myocardial
      revascularisation and better follow-up. For effective management, the diagnosis
      of coronary disease has to be established. The authors used a statistical model
      to study the efficacy of 4 diagnostic strategies used in daily practice: (i)
      three investigations in two stages: exercise stress testing, stress
      echocardiography or stress scintigraphy followed by coronary angiography when
      positive (EE, ECHO, SCINTI): (ii) one stage investigation: coronary angiography
      of first indication (CORO). When the a priori probability is low or moderate
      (less than 0.5) the efficacy of EE, ECHO and SCINTI is excellent as there are few
      false negative results. When the a priori probability of coronary disease is high
      (0.7 or more), the percentage of false negative results (patients with undetected
      significant coronary disease) becomes very high. At this level of risk the CORO
      strategy avoids the false negatives without increasing the costs with respect to
      the other strategies. In conclusion, the choice of diagnostic strategy of
      coronary artery disease should take into account the "a priori" risk of the
      patient. When high (> 0.7), coronary angiography of first intention seems to be
      statistically justified.

PMID- 9232071
TI  - [Orientated management towards reperfusion in the acute phase of myocardial
      infarction. Results in a cohort of 700 consecutive patients].
AB  - The principal objective of treatment of the acute phase of myocardial infarction
      is the obtention of TIMI 3 complete patency. Usually, only a minority of patients
      receives thrombolytic therapy and complete reperfusion in unusual. Between June
      1988 and April 1996, 700 consecutive patients were admitted to Bichat hospital
      within 6 hours of the onset of transmural myocardial infarction (81% men; age 59
      +/- 13 years). The objective of treatment was to obtain maximal coronary patency
      in the acute phase, either by thrombolysis (with systematic angiography at 90
      minutes and salvage angioplasty in case of failure), or primary angioplasty or
      conventional treatment (usually in cases of spontaneous reperfusion). The
      emergency angiography and angioplasty procedures were performed by a medical team
      on 24 hour duty. During the acute phase, 316 patients received intravenous
      thrombolysis (angiography at 90' in 302 patients with salvage angioplasty in 79
      patients), 304 underwent primary angioplasty (TIMI 3 artery in 85% of cases) and
      80 underwent conventional treatment (including 52 cases of angiographically
      documented spontaneous reperfusion). Therefore, a 81% (566/700) rate of patent
      TIMI 3 arteries was obtained. The hospital mortality was 8.9%, lower in TIMI 3
      arterial patency (6%) than TIMI 2 (20%) or TIMI 0-1 (23%), p < 0.001. The
      mortality was 4% in patients treated by thrombolysis. Therefore, a reperfusion
      strategy associating thrombolysis and/or angioplasty provides a high TIMI 3
      patency rate in the acute phase of myocardial infarction with a low mortality
      (6%) in consecutive, unselected patients.

PMID- 9232072
TI  - [What myocardial protection to select for isolated aortic valve replacement? A
      clinical prospective study of 3 cases of cardioplegia].
AB  - Isolated stenosis of the aortic valve leads to left ventricular hypertrophy which
      makes myocardial protection difficult during cardiac, surgery and the choice of
      optimal cardioplegia remains controversial. The authors compared three protocols
      of cardioplegia in patients operated for isolated aortic stenosis with left
      ventricular hypertrophy. Sixty consecutive patients with these criteria were
      randomly attributed to one of the three following groups (20 in each group):
      cardioplegia with continuous warm blood; cardioplegia with intermittent cold
      blood with warm reperfusion; cardioplegia with intermittent cristalloid using
      SLF11 solution. The preoperative data was comparable in three groups. There were
      no deaths. Patients undergoing cardioplegia with warm blood came off cardio
      pulmonary bypass more quickly (15 mn vs 21 mn for the other groups, p = 0.03).
      Cristalloid cardioplegia was associated with major acidosis in coronary sinus
      blood when the aorta was declamped (7.11 vs 7.38 for cardioplegia with cold blood
      and 7.39 for cardioplegia with warm blood, p < 0.0001) but with a low
      postoperative CPK-MB rise. Cardioplegia with cold blood induced higher CPK-MB
      liberation than the other forms of cardioplegia (at H-, 63 mcg/L vs 33 for warm
      blood and 45 for cristalloid cardioplegia, p = 0.0019). None of the protocols
      tested prevented myocardial lactate production at aortic declamping. Cardioplegia
      with warm blood offers therefore the best protection for hypertrophied myocardium
      during simple aortic valve replacement but it does not maintain strictly aerobic
      metabolism.

PMID- 9232073
TI  - [Endocoronary ultrasonography and quantitative coronary angiography. Correlations
      before and after transluminal coronary angioplasty].
AB  - A comparative study of the results of quantitative coronary angiography and
      endocoronary ultrasonography was performed in 37 patients undergoing percutaneous
      transluminal coronary angioplasty to determine the correlations between the two
      methods. The analyses were made before and after angioplasty at the site of
      stenosis and on a reference segment. A complete study before and after
      angioplasty using both techniques was only possible in 24 cases. The quantitative
      ultrasonographic analysis consisted of measurement of two orthogonal diameters,
      total surface area of the vessel, the endoluminal surface area and surface area
      of plaque. Transluminal coronary angioplasty acts mainly by forcing the plaque
      outwards. Ultrasonography showed a decrease in plaque area, from 10.5 +/- 6 mm2
      to 9.8 +/- 5.5 mm2 and the total surface area of the vessel increased from 12.8
      +/- 0.7 to 15.3 +/- 6.9 mm2 (p < 0.05). This accounted for the gain in main
      surface area of the stenosed lumen, from 2.28 +/- 1.28 to 5.9 +/- 2.65 mm2 (p <
      0.001). The correlations between quantitative coronary angiography and
      ultrasonography at the site of stenosis were only significant after angioplasty
      both the vessel diameter (r = 0.67; p < 0.0002) and endoluminal surface area (r =
      0.63; p < 0.0001). A correlation was not observed before angioplasty because of
      the complexity of the plaque and its excentric location. At the reference site,
      the correlations between ultrasonography and angiography before and after
      angioplasty were significant but not very close (Spearman coefficient 0.53 and
      0.82 respectively, p < 0.001). Therefore, correlations between quantitative data
      obtained by coronary angiography and ultrasonography are modest in patients
      undergoing transluminal coronary angioplasty. The ultrasonographic information is
      more qualitative, enabling a better understanding of the mechanism of the
      therapeutic procedure and allowing optimal choice of the appropriate tool.

PMID- 9232075
TI  - [Treatment of congenital heart diseases with pulmonary artery cerclage. Immediate
      and medium term results in 51 patients].
AB  - The aim of this study was to assess the results of pulmonary artery banding in a
      retrospective study of 51 consecutive children treated from January 1980 to
      December 1993. The study population was 24 girls and 27 boys with an average age
      of 6.2 months, of average weight of 4.01 kg. The cardiac conditions treated were
      ventricular septal defects in 24 cases (isolated and associated with one or more
      cardiovascular malformations or multiple), complete atrioventricular canal in 12
      cases (isolated or associated with several cardiovascular malformations), single
      ventricle in 7 cases, double outlet right ventricle in 3 cases, transposition of
      the great arteries with ventricular septal defect in 2 cases, tricuspid atresia
      in 2 cases, and a complex lesion with double discordance in one case. The average
      duration of banding was 2.35 years (n = 49). Hospital morality of banding was
      1.9% (1/51). Late mortality was 14.8% (7/47). Twenty-one patients (42.8%) had
      complications of banding. The survival rates of children who underwent banding
      was 86.8% at 1 year and 80.6% at 11 years. The low hospital mortality leaves a
      role for pulmonary artery banding as a palliative procedure in congenital heart
      disease in which early correction is impossible or carries and unacceptable risk.
      Complications of banding justify attempts to improve the technique, by making
      adjustable bands.

PMID- 9232074
TI  - [Clinical, echocardiographic and Doppler outcome in ischemic right ventricular
      dysfunction associated with inferior wall infarction].
AB  - Right ventricular involvement during inferior wall myocardial infarction does not
      seem to alter long-term clinical prognosis but its specific outcome has not been
      clearly studied. We have previously demonstrated that pulmonary regurgitant (PR)
      flow tracings doppler analysis allows the accurate diagnosis of RV involvement,
      especially when the pressure half-time of PR was < or = 150 ms and the ratio of
      the minimal velocity to the maximal velocity was < or = 0.5. We studied 40
      patients with acute inferior wall myocardial infarction and with PR flow. Doppler
      echocardiography was obtained during the first day, before discharge (early
      control) and between 12 and 24 months follow-up (late control). Among 22 patients
      with RV involvement defined with PR-derived doppler parameters (RVIPR). 8 had
      right ventricular enlargement and/or wall motion abnormalities, observed in 6
      cases at early control and in 4 at late control. Doppler analysis showed remnant
      RVIPR parameters in 9 patients at early control and 8 among these at late
      contorl, with no relation with pulmonary artery pressure or other
      echocardiographic parameters. No clinical, angiographic or therapeutic data
      predicted these distinct echocardiographic and doppler patterns and the long-term
      prognosis was not different. At late control, among 12 RVIPR patients which PR
      derived doppler parameters were normal at early control, two patients had still
      RVIPR pattern at late control and described ischemic recurrence. PR flow doppler
      analysis is a useful tool for diagnosis and outcome evaluation of RV involvement
      and shows a remnant diastolic dysfunction in half of the patients with acute RV
      involvement.

PMID- 9232076
TI  - [Radiofrequency ablation of resistant atrial flutter: a new anatomical approach].
AB  - Several reports have suggested that radiofrequency ablation could prevent atrial
      flutter resistant to antiarrhythmic therapy. The usual recommendation is to apply
      the radiofrequency current in a zone situated between the tricuspid valve and
      orifice of inferior vena cava. The aim of this study was to assess the efficacy
      of another site of ablation of flutter extending from the tricuspid valve to the
      orifice of the coronary sinus, either alone or associated with a site between the
      coronary sinus and the lateral wall of the right atrium. Twenty patients aged 42
      to 78 years (mean : 6 +/- 11 years) were included. Atrial flutter was paroxysmal
      in 15 patients and chronic in 5 patients. Each patients had documented failure of
      1 to 5 antiarrhythmic agents (average 3.1 +/- 1.6). The site of ablation was
      localised by anatomical criteria alone. During follow-up of 7 +/- 5 months (range
      1 to 18 months), 13 patients had no recurrence of atrial flutter after ablation,
      5 patients had recurrence and 2 patients had paroxysmal atrial fibrillation
      alone: the success rate was 15/20 (75%). This study suggests that the zone
      between the tricuspid valve and coronary sinus may be a site for radiofrequency
      ablation of atrial flutter. It is valuable alternative to the usually recommended
      technique.

PMID- 9232077
TI  - [Clinical, experimental and physiopathological aspects of restenosis after
      coronary angioplasty].
AB  - Restenosis is still the main limitation of coronary angioplasty. A comparison of
      clinical data and experimental observations from animal models showed the early,
      local and transient features of this phenomenon. Several hypotheses have been
      advanced to explain the mechanism. Intimal hyperplasia remains an important
      feature of restenosis in the human but probably does not play the exclusive role
      as used to be believed. Vascular remodelling which has several mechanisms seems
      to be a major contribution to reduction of the vessel lumen. The role of
      thrombosis remains controversial in the clinical setting but is an essential
      factor in the pig which is a very similar model to the human. Each of these
      different mechanisms participates in the development of restenosis but in
      proportion which remain to be defined.

PMID- 9232078
TI  - [Complete atrioventricular block disclosing Fabry's disease].
AB  - Fabry's disease is a hereditary sex-linked sphinglopidosis characterised by
      abnormal cellular lipid overload in most organs due to deficiencies in enzymes
      implicated in the catabolism of certain neutral glycolipids. There are two main
      clinical forms; cardiovascular manifestations usually congestive cardiac failure,
      and renal manifestations progressing to renal failure and death due to uraemic
      coma. The authors report a case presenting with juvenile, symptomatic complete
      infrahisian atrioventricular block. They describe the different cardiovascular
      complications of Fabry's disease from a review of the medical literature.

PMID- 9232079
TI  - [Value of MRI with injection of gadolinium in the diagnosis of mitral ring
      abscess. Apropos of a case].
AB  - Transoesophageal echocardiography is the investigation of choice for the
      diagnosis of valvular vegetations in infectious endocarditis but the diagnosis of
      an associated ring abscess is sometimes difficult especially in patients with
      valvular prostheses or calcifications which are in important source of artefacts.
      The authors report a case of mitral annular abscess confirmed at surgery and
      comment on the diagnostic and prognostic value of cardiac MRI. MRI showed an
      abnormal cavity directly related to the mitral annulus and separated from the
      left ventricle by a low intensity signal which increased after injection of
      gadolinium suggesting an inflammatory origin and therefore arising from the
      abscess. The cavity was heterogeneous in T1 associating zones of low intensity
      with high intensity signals increasing in T2 on the second echo (thrombus and
      necrosis). Cine-MRI showed non communication between the abscess cavity and the
      left ventricle or atrium.

PMID- 9232081
TI  - [Ventricular fibrillation after radiofrequency ablation of the atrioventricular
      node].
AB  - The authors report the case of a 77 year old patient who underwent radiofrequency
      ablation of the atrioventricular node for chronic. Invalidating atrial
      fibrillation, refractory to pharmacological therapy. A single chamber ventricular
      pacemaker was implanted one week before interruption of AV conduction. Eleven
      applications (7 on the right and 4 on the left side of the interventricular
      septum) were required for successful ablation. Four hours later, the patient
      developed episodes of non-sustained polymorphic ventricular tachycardia and
      torsades de pointe. These arrhythmias were initiated by long cycle-short cycle
      sequences and preceded by changes of ventricular repolarisation (prolongation of
      the spontaneous and paced QTc and JTc intervals). Eight days after ablation, the
      patient had an episode of ventricular fibrillation reduced by external DC shock.
      This arrhythmia was also preceded by changes in ventricular repolarisation. This
      case demonstrates the potential proarrhythmogenic effect of radiofrequency
      ablation of the AV node with changes in ventricular repolarisation which induces
      malignant ventricular arrhythmias. The authors suggest an appropriate preventive
      attitude. The progression in two distinct phases (immediate and late) imposes
      prolonged arrhythmia monitoring.

PMID- 9232080
TI  - [Fetal supraventricular tachycardia with anasarca complicating benign
      extrasystole: treatment with flecainide. Apropos of a case].
AB  - We report a case of fetal supraventricular tachycardia with intra-uterine cardiac
      failure, who complicate benign premature beats. It was treated with oral
      administration of flecainide acetate (Flecaine) to the mother. This treatment was
      rapidly effective. The fetus converted to sinus rhythm in 5 days and the ascites
      had completely resolved in 10 days. We conclude, that fetus with premature beats
      must be observed every 15 days, and we believe that flecainide acetate can be
      used as the "first line agent" to the fetal supraventricular tachycardias with
      cardiac failure.

PMID- 9232082
TI  - [Daniel Kalmanson (1927-1996)].

PMID- 9232083
TI  - Power and gender: violence and affection experienced by children in Barbados,
      West Indies.
AB  - Discourses on violence conceptualize the phenomenon as a property of (1)
      individuals, (2) social circumstances, and (3) social relationships. Rigorous
      comparative tests fail to support the first and second hypotheses. Survey data
      collected in 1990 from a national random sample of 407 men and women aged twenty
      to forty-five from the West Indian island of Barbados indicate that one of four
      experienced physical and emotional violence as children. Boys and girls were
      equally likely to be abused by both mothers (or other female caregivers) and
      fathers (or other male caregivers); stepparents were no more likely to treat
      children violently than were biological parents. However, the presence of a
      stepfather increased the likelihood that women battered their daughters and
      decreased the likelihood that women battered their sons. In general, powerful
      women protected their children from violence, treated them affectionately, and
      elicited affection for them from their men. The probability that a son
      experienced an affectionate relationship with a biological father rose with the
      length of time the two lived together, but only for sons with powerful mothers.
      By contrast, men battered powerless women and the children of powerless women.
      Powerless women battered their own children.

PMID- 9232084
TI  - Bringing political ecology into critical medical anthropology: a challenge to
      biocultural approaches.
AB  - This essay presents an effort to incorporate the "environment" into critical
      medical anthropology. Rather than relying upon the multifactorial approach
      characteristic of medical ecology or biocultural approaches in medical
      anthropology, it urges critical medical anthropologists to turn to the burgeoning
      literature on eco-Marxism, eco-socialism, or political ecology in their efforts
      to develop a political ecology of health. Given that political ecologists
      generally advocate democratic eco-socialism as a meaningful alternative to the
      capitalist world system, this essay also presents a critical examination of the
      environmental record of post-revolutionary societies.

PMID- 9232085
TI  - A changing Hausa diet.
AB  - We report results of a longitudinal study of shifting patterns of food
      consumption in a rural Hausa-Fulani village in northern Nigeria. While the broad
      outlines of diet did not change over the 12 years between two dietary surveys,
      important shifts occurred: a decline in the consumption of local cultigens, with
      a corresponding decrease in total caloric intake, as well as an embellishment of
      diet through the introduction of new foods. We suggest that this is best
      understood through the growing participation of this village in the wider
      economy. We juxtapose these dietary shifts to a model of disease risk that
      suggests, for the early period, that the coincidence of dietary elaboration and
      the periodicity of disease risk offered some degree of protection against malaria
      infection. For the more recent period, diet was no longer marked by conspicuous
      seasonal changes. To what extent these differences in diet patterns have affected
      the disease experience of this population is not yet clear.

PMID- 9232086
TI  - Sociocultural and behavioral influences on health status among the Mississippi
      Choctaw.
AB  - Native American populations in North America are at increased risk of a variety
      of health problems, including (but not limited to) diabetes. This risk is
      presumed to be a result of the interaction of environmental influences with a
      population genetic susceptibility. Anthropologists have subsumed those
      environmental influences under the term "acculturation." Here, we break that
      broad concept into physical, behavioral, and sociocultural components in an
      examination of the correlates of arterial blood pressure and plasma glucose among
      the Mississippi Choctaw. In a sample of 93 adults, higher plasma glucose was
      associated with the lower physical activity, higher body mass index, and higher
      lifestyle incongruity, after controlling for age, sex, and recency of food
      consumption. Higher arterial blood pressure was associated with higher body mass
      index and being single. These results suggest that the risk of disordered glucose
      metabolism within this Native American population is associated with
      acculturation broadly construed, but that refined models of health and disease
      must take into account the multiple dimensions of this concept. Physical,
      behavioral, and sociocultural factors combine to describe more precisely the
      concept of acculturation, and hence the factors contributing to the risk of
      disease in Native American communities.

PMID- 9232088
TI  - Pulmonary embolism in deep venous thrombosis of the upper extremity: more often
      in catheter-related thrombosis.
AB  - BACKGROUND: Pulmonary embolism (PE) is a major complication of deep venous
      thrombosis (DVT) of the lower extremities. The incidence is approximately 50%.
      The incidence of DVT of the upper extremity (DVTUE) is increasing mainly due to
      the increasing use of central venous catheters. The percentage of PE secondary to
      DVTUE is still being investigated. METHODS: The occurrence of PE in DVTUE was
      retrospectively analyzed in 78 patients with proven DVTUE. Furthermore, the
      literature was reviewed. RESULTS: Of the identified patients with DVTUE 16 showed
      a primary DVTUE and 62 a secondary DVTUE. Secondary DVTUE was catheter-related in
      41 (60%), which is 53% of all DVTUE. In this study the percentage of PE as a
      complication of DVTUE was 6 (95% CI: 0.2-30) in primary DVTUE, 13 (95% CI: 6-24)
      in secondary DVTUE and 17 (95% CI: 7-32) in catheter-related DVTUE. The relative
      risk for PE of catheter-related DVTUE versus other causes was 3.4 (95% CI: 0.4
      53.5). The overall percentage was 12 (95% CI: 5-21). The literature review showed
      a percentage of 7 (95% CI: 4-9) in the retrospective studies and 17 (95% CI: 12
      23) in the prospective studies. CONCLUSIONS: Indwelling catheters are the most
      common cause of DVTUE. PE is not an uncommon complication of DVTUE, and is more
      common in catheter-related DVTUE. The difference between the incidence of PE in
      DVTUE and DVT of the lower extremity may be explained by a number of factors,
      such as differences in fibrinolytic activity, mechanical forces and venous flow
      patterns.

PMID- 9232087
TI  - The effects of inhaled glucocorticoids on bone mass and biochemical markers of
      bone homeostasis: a 1-year study of beclomethasone versus budesonide.
AB  - Bone mass and biochemical bone markers were prospectively studied in 33 patients
      with chronic obstructive pulmonary disease treated for 1 year with inhaled
      beclomethasone 200 micrograms/q.i.d. (group A, 8 men and 4 women), inhaled
      budesonide 200 micrograms/q.i.d. (group B, 6 men and 5 women), or not requiring
      steroids (group C, 6 men and 4 women). Both inhaled corticosteroids decreased
      serum concentrations of the osteoblastic markers, osteocalcin and carboxy
      terminal propeptide of type I collagen (PICP). The osteoclastic marker cross
      linked carboxy-terminal telopeptide of type I collagen (ICTP) increased
      significantly more in patients on beclomethasone than in those on budesonide. The
      decrease in bone mineral density was more pronounced in patients treated with
      beclomethasone (1.1% in the spine 1.7% in the hip P < 0.05) compared to those
      treated with budesonide (0.6% in both spine and hip) or in the control group.
      Inhaled corticosteroids affect biochemical bone markers and bone mineral density,
      but there is a different effect for the two corticosteroids evaluated in the
      present study.

PMID- 9232089
TI  - Syndrome of inappropriate ADH secretion attributed to the serotonin re-uptake
      inhibitors, venlafaxine and paroxetine.
AB  - We report on 2 patients with the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) which developed a few weeks after they had started
      treatment with venlafaxine and paroxetine, respectively. Due to the temporal
      relationship and the exclusion of other potential causes, a causal relationship
      between the use of the antidepressants and SIADH seems likely. Diagnostic
      criteria for SIADH and the role of drugs, especially serotonin re-uptake
      inhibitors, are discussed.

PMID- 9232090
TI  - Successful catheter drainage of recurrent benign multicystic mesothelioma of the
      peritoneum.
AB  - The case history of a patient with pulmonary embolism 4 months following a kidney
      transplantation is presented. Ultrasonography of the abdomen suggested a large
      ovarian tumour for which she had a laparotomy. Histological examination after
      resection of the tumour revealed a benign multicystic mesothelioma of the
      peritoneum. During the course of 1 year the tumour recurred 5 times and different
      attempts to aspirate and obliterate the cyst were ineffective. Eventually, cure
      was achieved by permanent transvaginal catheter drainage, which resulted in
      infection and obliteration of the cyst.

PMID- 9232091
TI  - Duodenal diverticulitis.
AB  - The case history of a 56-year-old woman with an acute abdomen is presented.
      Laboratory data, a plain abdominal X-ray and ultrasound examination provided no
      clues for a definite diagnosis. Surprisingly, a duodenal diverticulitis was found
      at operation. Some aspects and complications of duodenal diverticula are
      discussed.

PMID- 9232092
TI  - Effects of inhaled corticosteroids on bone.
AB  - Inhaled corticosteroids (ICS) are the most effective therapy for asthma currently
      available. The increasing use of ICS raises the issue of possible adverse
      systemic effects. Since one of the most important side-effects of oral
      corticosteroids (OCS) is osteoporosis, this article focuses on current knowledge
      of the effects of ICS on bone. Generally, doses higher than 1.0 mg/day cause a
      dose-dependent decrease in serum osteocalcin levels. Decreases in bone density
      have been suggested after treatment with ICS, but in most studies it is
      impossible to quantify the contribution of previous treatment with OCS and other
      confounding factors to bone loss. The clinical relevance of the observed changes
      in the long term is unknown. To date, no fracture data have been reported in
      patients. Beclomethasone dipropionate, budesonide and fluticasone propionate do
      not appear to be different per milligram ICS. In general, the lowest clinically
      efficacious dosage of ICS should be aimed at.

PMID- 9232093
TI  - A survey of the diagnostic and therapeutic management of patients with suspected
      pulmonary embolism in the Netherlands.
AB  - BACKGROUND: Pulmonary embolism (PE) remains a complex diagnostic problem. Many
      diagnostic modalities are available. Several published guidelines have failed to
      yield a uniform approach. We have assessed the current diagnostic and therapeutic
      management of patients with clinically suspected PE in the Netherlands. METHODS:
      A questionnaire was sent to internists and pulmonologists, who were then asked to
      detail their diagnostic and therapeutic management in their last patient seen
      with suspected PE. RESULTS: 1571 questionnaires were sent out (response rate
      64%). 95% of the patients with suspected PE underwent a perfusion scan (in 91%
      within 24 h). 1.6% of the respondents had no available perfusion scan facility.
      Of those who underwent a perfusion scan, 62% had ventilation scan (66% with
      segmental defects, 80% with subsegmental defects, 27% with a normal perfusion
      scan). Tests for deep vein thrombosis were performed in 58% of the patients and
      pulmonary angiography was carried out in 6.1%. Anticoagulant treatment was
      instituted in 73.2% of all patients. CONCLUSIONS: The perfusion lung scan is
      appropriately used as the initial step in the diagnostic workup of patients with
      suspected PE. Ventilation scanning is overused in patients with subsegmental
      perfusion defects and normal scan results, whereas it is underused in patients
      with segmental defects. Additional ventilation scan results had a limited
      influence on treatment decisions. There is still considerable overtreatment of
      patients with suspected PE.

PMID- 9232094
TI  - Changes in regional cortical temperature and cerebral blood flow after cortical
      spreading depression.
AB  - Regional cerebral blood flow (rCBF) measurement by laser Doppler flowmetry and
      cortical temperature measurement using thermoencephaloscopy (TES) were performed
      to investigate the relationship between the changes in rCBF and cortical
      temperature after induced cortical spreading depression (CSD) in rats. TES showed
      a gradually expanding thermoresponse like an extending circular wave after CSD
      induced by application of KCl. Similarly, a transient increase in rCBF spread
      from the site of stimulation with a velocity of propagation of 2.5 mm/min.
      Simultaneous monitoring of rCBF and cortical temperature showed that the
      transient increase in rCBF was associated with an initial decrease in cortical
      temperature, followed by an increase in cortical temperature. We suggest that the
      cortical temperature is regulated mainly by neurogenic control of the pial
      microvascular blood supply that is precisely adjusted to the metabolic needs of
      the cerebral cortex. Non-injured cortex with the fine vascular architecture must
      be preserved during neurosurgery to allow heat transfer from deep areas of the
      cortex.

PMID- 9232095
TI  - Effects of repeated short versus single long episodes of focal ischemia on
      somatosensory evoked potentials and development of cerebral infarction in cats.
AB  - The effects of repeated short episodes of focal ischemia at 30-minute intervals
      or a single equivalent long episode of focal ischemia on neuronal function and
      development of cerebral infarction were compared using somatosensory evoked
      potential (SEP) recording and 2,3,5-triphenyltetrazolium chloride staining in a
      cat model. Seventeen cats underwent transorbital occlusion of the middle cerebral
      artery (MCA), using one of three procedures: sham-operation; single 1-hour
      occlusion of the MCA, followed by 3 hours of recirculation; or three 20-minute
      occlusions of the MCA at 30-minute intervals, followed by 3 hours of
      recirculation. Two of six cats in the single long-term occlusion group showed
      recovery of SEP, whereas all six cats in the repeated short-term occlusion group
      showed recovery of SEP at 3 hours after recirculation. All six cats in the single
      long-term occlusion group had cerebral infarction of various sizes, but only one
      cat in the repeated short-term occlusion group developed infarction. Repeated
      short episodes of focal ischemia are relatively less damaging than a single
      equivalent long episode of focal ischemia, even if the reperfusion interval is
      extended to 30 minutes.

PMID- 9232096
TI  - Sonic analysis for detection of cervical and intracranial vascular disease.
AB  - A sonic analysis system was developed for the detection of cervical and
      intracranial vascular disease. The system analyzes recorded sound signals
      converted to digital data, and plots the frequency, time interval after the QRS
      wave of the electrocardiogram, and amplitude on the graph using contour lines.
      Sonic analysis of 22 patients with and 23 patients without cerebrovascular
      disease identified a characteristic pattern of disease called the "circular
      pattern." Five of 10 patients with internal carotid artery stenosis, four of
      seven with cerebral aneurysms, three with cerebral arteriovenous malformation,
      and two of two with dural arteriovenous malformation showed the circular pattern.
      Only one of 23 control patients showed the circular pattern. This system is a
      promising method for cost-effective mass screening for the early detection of
      cerebrovascular disease.

PMID- 9232097
TI  - Choroidal detachment and dural carotid-cavernous sinus fistula--case report.
AB  - A 71-year-old female presented with the rare complication of choroidal detachment
      after endovascular treatment of a dural carotid-cavernous sinus fistula. Since
      the residual arteriovenous shunt flow was minimal and intraocular pressure was
      normal, the choroidal detachment was treated conservatively and disappeared
      within one month. The possibility of choroidal detachment during the clinical
      course of a dural carotid-cavernous sinus fistula should be recognized.

PMID- 9232098
TI  - Sinus pericranii associated with a cerebellar venous angioma--case report.
AB  - A 64-year-old male presented with sinus pericranii associated with a venous
      angioma draining through a large venous lake. Increased venous pressure and flow
      in the dural venous lake in contact with the venous sinus may have developed the
      sinus pericranii. Three-dimensional computed tomography was very useful in
      determining the site of the transcranial venous anastomotic channels, and
      magnetic resonance imaging was also very useful in detecting the intracranial
      vascular anomalies.

PMID- 9232099
TI  - Hypothalamic hamartoma associated with dural arteriovenous fistula of the
      transverse-sigmoid sinus--case report.
AB  - A 32-year-old female presented with a hypothalamic hamartoma associated with a
      dural arteriovenous fistula (DAVF) of the left transverse-sigmoid sinus. She
      complained of pulsatile tinnitus in the left retroauricular region and
      infertility. Endocrinological examination revealed that the luteinizing hormone
      reaction to luteinizing hormone-releasing hormone was exceedingly high. Magnetic
      resonance imaging demonstrated a distinct mass occupying the suprasellar cistern
      and protruding into the third ventricle. Left carotid angiography demonstrated a
      DAVF of the left transverse-sigmoid sinus, which was treated by embolization.
      Histological examination of a biopsy specimen of the tumor revealed a hamartoma.
      She was free from pulsatile tinnitus after treatment for the DAVF.

PMID- 9232101
TI  - Intracranial tuberculoma mimicking metastasis from renal tumor--case report.
AB  - A 63-year-old female presented with intracranial tuberculoma manifesting as
      severe headache. Systemic examination found a mass in the left kidney. The
      histological diagnosis was tuberculoma after kidney biopsy. Cranial computed
      tomography found two lesions, in the right frontal and occipital lobes. The
      intracranial lesions were considered to be tuberculomas. Tuberculosis
      chemotherapy was continued for 15 months. Her neurological deficit was resolved.
      Cranial computed tomography showed the lesion in the frontal lobe had disappeared
      and the lesion in the occipital lobe was reduced in size.

PMID- 9232102
TI  - Immunohistochemical detection of tumor marker in recurrent clivus enterogenous
      cyst--case report.
AB  - A 26-year-old male presented with recurrence of an enterogenous cyst in the
      intracranial region 10 years after the first operation. The cyst was drained and
      the cyst wall partially resected at both operations with good outcome.
      Histological examination showed a change from one layer epithelium in the first
      specimen to glandular structures in the second. Alcian blue, periodic acid
      Schiff, and immunohistochemical staining for epithelial membrane antigen, S-100
      protein antigen, keratin, and carcinoembryonic antigen were used to confirm the
      accurate diagnosis. Immunohistochemical staining showed CA19-9 antigen was
      positive in both specimens. The CA19-9 level in the cerebrospinal fluid was
      extremely high (621.5 U/ml) at the second operation. Patients with enterogenous
      cyst should be monitored to detect possible recurrence.

PMID- 9232100
TI  - Petrous bone meningioma originating from the jugular foramen--case report.
AB  - A 49-year-old female presented with a rare meningioma in the petrous bone. High
      resolution computed tomography and magnetic resonance imaging demonstrated that
      the tumor had developed in the jugular foramen and extended into the
      infralabyrinthine area of the petrous bone and intracranially into the
      cerebellopontine angle. The operative findings confirmed these observations.
      Meningiomas of the petrous bone may originate from the jugular foramen.

PMID- 9232103
TI  - Global health care and neurosurgeons.
AB  - The contributions that neurosurgeons can make to global health are discussed in
      the context of the author's clinical and research experience, his views on
      priorities and equity in research and economic development, and the state of
      health care in developed and developing countries. Ideas for establishing a new
      paradigm of health care for all are proposed, as well as more general
      interventions on behalf of human rights and peace. Neurosurgeons, other medical
      professionals, and those who are concerned about these global issues are urged to
      work in concert to remove inequalities in health care both locally and globally.

PMID- 9232104
TI  - Interview with Bonnie Kelly. Interview by Robin K. Levinson.

PMID- 9232105
TI  - Hope on the horizon for Alzheimer's patients.

PMID- 9232106
TI  - Malaria: experience at two hospitals.

PMID- 9232107
TI  - Cardiac paraganglioma in New Jersey.

PMID- 9232108
TI  - Safety in the workplace: OSHA inspections.

PMID- 9232109
TI  - The introduction of "606" in New Jersey.

PMID- 9232111
TI  - Educational excellence from AMNJ.

PMID- 9232110
TI  - Computer-integrated surgery.

PMID- 9232112
TI  - Detection of equine X chromosome abnormalities in equids using a horse X whole
      chromosome paint probe (WCPP).

PMID- 9232113
TI  - The pregnancy that doesn't stay--lessons from 25 years of observation.

PMID- 9232114
TI  - Paratuberculosis and molecular biology.

PMID- 9232115
TI  - Chlamydial disease--more than just abortion.

PMID- 9232116
TI  - Herpesviral abortion in domestic animals.
AB  - Abortion or neonatal disease may follow infection with several alpha, beta and
      gamma-herpesviruses. The alpha-herpesvirus, equid herpesvirus-1 (EHV-1), causes
      single or epizootic abortions or neonatal deaths in equids, and the closely
      related virus EHV-4 causes sporadic equine abortions. In cattle, the alpha
      herpesviruses, bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) and
      bovine herpesvirus-5 (bovine encephalitis virus), and a gamma-herpesvirus, bovine
      herpesvirus-4, have all been implicated as causes of abortion. In pigs, suid
      herpesvirus-1 (SHV-1: pseudorabies virus), an alpha-herpesvirus, and SHV-2
      (porcine cytomegalovirus), a beta-herpesvirus, each cause abortion or neonatal
      piglet losses. Caprine herpesvirus-1, canine herpesvirus and feline herpesvirus
      1, all alpha-herpesviruses, cause abortions or neonatal deaths in goats, dogs and
      cats, respectively. This review discusses the pathogenesis, pathology and
      laboratory diagnosis of these herpesviral abortions and neonatal diseases, with
      an emphasis on experimental studies of each disease. Alternative reviews covering
      other aspects of each infection, such as the genetic and antigenic structure of
      the viruses, host immune responses and approaches to vaccination and disease
      control are indicated at appropriate points in the text.

PMID- 9232117
TI  - The contribution of molecular biology to Mycobacterium avium subspecies
      Paratuberculosis research.
AB  - Molecular biology has contributed to our knowledge and understanding of the
      structure of Mycobacterium avium subspecies paratuberculosis and has been
      particularly useful in determining those components that elicit immune responses
      in the host or discriminate M. avium paratuberculosis from other closely related
      environmental mycobacteria. As such, it has made a significant impact in the
      field of diagnosis, and has been instrumental in the development of specific and
      sensitive diagnostic tests. The next decade will see exciting new developments in
      paratuberculosis research as a consequence of substantial advances made in the
      construction of gene transfer systems in mycobacteria. These will provide
      opportunities for applying new strategies to determine the genetic basis for
      pathogenesis and the mechanisms of drug resistance and will offer new prospects
      for the rational design of efficient vaccines.

PMID- 9232118
TI  - Detection of animal pathogens by using the polymerase chain reaction (PCR).
AB  - The polymerase chain reaction (PCR) is a nucleic acid-based technique that
      enables the rapid and sensitive detection of specific micro-organisms. Although
      this technique is widely used in veterinary research, it has not yet found
      applications in routine microbiological analysis of veterinary clinical samples.
      However, advances in sample preparation together with the increasing availability
      of specific gene sequences will probably lead to the more widespread diagnostic
      use of PCR in the future. PCR is likely to have a strong impact in the
      epidemiology, treatment and prevention of animal infectious diseases.

PMID- 9232119
TI  - Isolation of faecal chlamydia from sheep in Britain and their characterization by
      cultural properties.
AB  - Faeces samples were taken per rectum from sheep on 26 farms in England and Wales
      and examined for the presence of chlamydia by culture in McCoy cell monolayers.
      Thirteen of the farms were known to have had abortion outbreaks associated with
      Chlamydia psittaci (enzootic abortion) and 13 were free of this infection. The
      chlamydia isolated were characterized by cultural techniques. Chlamydia were
      isolated from the faeces of lambs on all 26 farms and the prevalence of infection
      varied form 5-50% on individual farms. There was no significant difference
      between the proportion of infected lambs on farms where enzootic abortion was
      present or absent. Lambs first showed infection when they were 3 months old and
      the prevalence rate of infection increased up to 9 months old. No chlamydia were
      isolated from the faeces of 316 adult ewes. The chlamydia were identified as
      enteric rather than abortion type and thus were C. pecorum rather than C.
      psittaci.

PMID- 9232120
TI  - Functional anatomy observations of the pharyngeal orifice of the equine guttural
      pouch (auditory tube diverticulum).
AB  - The pharyngeal orifice of the equine auditory tube has not been adequately
      described. Its larger size and position, further rostral within the nasopharynx
      compared with other species, cannot be easily explained, but could be important
      for the proposed brain-cooling function of the guttural pouches; however, unlike
      other species, it may not be the sole regulator of auditory tube aeration. A
      'second orifice' (representing the final entrance to the auditory tube
      diverticulum) deserves recognition in performing a role in air exchange between
      the auditory tube, diverticulum and middle ear. The results of this investigation
      suggest that regular guttural pouch ventilation during resting respiration does
      not occur. Previous reports may reflect, at least in part, a misinterpretation of
      air pressure measurements within the guttural pouches and nasopharynx. Small
      decreases in simulated inspiratory pressure consistently caused the passive
      opening of both the pharyngeal orifice and pouch ostium in horse cadavers
      suggesting that an active counter process may exist in the live horse to maintain
      closure of the guttural pouch openings during rest and light exercise. Intrinsic
      tone of the stylopharyngeus and pterygopharyngeus muscles may be part of this
      active process. The investigation offers theoretical evidence that opening of the
      equine auditory tubes to ventilate the guttural pouch occurs in two different
      ways, active and passive. The active process has two stages: (1) opening of the
      pharyngeal orifices by simultaneous contractions of the levator and tensor veli
      palatini and pterygopharyngeus muscles; then (2) opening of the pouch ostia by
      contractions of dorsal portions of the palatopharyngeus muscles. The alternative
      passive route involves reduction in tone of the stylopharyngeus and
      pterygopharyngeus muscles accompanied by increased inspiratory pressure.

PMID- 9232121
TI  - Endotoxaemia in dairy cattle: mechanism of reticulorumen stasis.
AB  - The objective of this study was to determine whether blockade of alpha(-2)
      adrenergic receptors would restore reticulorumen motility during toxaemia in
      cows. Reticulorumen contractions were measured via a water-filled balloon
      connected to a pressure transducer. Intravenous infusion of endotoxin (100 ng kg
      1 over 30 min) significantly decreased the number of reticulorumen contractions.
      Intravenous infusion of yohimbine (125 micrograms kg-1 over 30 min) alone did not
      affect reticulorumen contractions. However, when yohimbine (125 micrograms kg-1
      over 30 min) was infused concurrently with endotoxin (100 ng kg-1 over 30 min),
      the effects of endotoxin on reticulorumen contraction frequency decreased,
      suggesting that endotoxaemia causes reticulorumen stasis via a mechanism that
      involves alpha(-2) adrenergic receptors.

PMID- 9232122
TI  - Welfare implications of gas stunning pigs: 3. The time to loss of somatosensory
      evoked potentials and spontaneous electrocorticogram of pigs during exposure to
      gases.
AB  - Changes in the spontaneous electrocorticogram (ECoG) and somatosensory evoked
      potentials (SEPs) were recorded in 12 pigs in each of three gas killing
      treatments. The treatments were 90% argon in air with 2% residual oxygen; a
      mixture of 30% carbon dioxide and 60% argon in air with 2% residual oxygen; or 80
      90% carbon dioxide in air. The mean times to loss of SEPs were 15, 17 and 21 s,
      respectively. The mean time to loss of SEPs recorded during killing with a high
      concentration of carbon dioxide was significantly longer than those recorded for
      the other two gas killing treatments (P < 0.05). Slow waves (high amplitude and
      low frequency) appeared on average 15 s after exposure to argon. In some pigs
      killed with the carbon dioxide-argon mixture, a decrease in the frequency of
      electrical activity was apparent, although slow waves did not appear during
      killing with a higher concentration of carbon dioxide. A suppressed ECoG
      (reduction in amplitude of signals) was recorded at 22 and 20 s respectively,
      during exposure to the carbon dioxide-argon mixture and 80-90% carbon dioxide in
      air, but the onset of ECoG suppression could not be determined exactly during
      exposure to 90% argon in air. The time to onset of an isoelectric ECoG was 54,
      39d and 32 s after exposure to argon, carbon dioxide-argon mixture and a high
      concentration of carbon dioxide, respectively. The mean time to the onset of an
      isoelectric ECoG during exposure to argon was significantly longer than that
      recorded for the other two gas killing treatments (P < 0.05). Based on the time
      to loss of SEPs, it is concluded that during killing with a high concentration of
      carbon dioxide, pigs would have to endure a moderate to severe respiratory
      distress induced with this gas for a considerable period of time prior to the
      loss of brain responsiveness. Argon-induced anoxia appears to be the first choice
      from a welfare point of view for killing pigs, based on its lack of aversive
      properties and its effectiveness in rapidly abolishing brain responsiveness. A
      mixture of 30% carbon dioxide and 60% argon in air is considered to be more
      humane than using a high concentration of carbon dioxide, as the time to loss of
      brain responsiveness is similar to that using 90% argon in air.

PMID- 9232123
TI  - Age and hourly related changes of serum testosterone and spermiogram of
      prepubertal bulls fed two levels of nutrition.
AB  - Serum testosterone concentrations and the spermiograms of prepuberal bulls fed
      two levels of protein diets were investigated at 7, 10, 14 and 18 months of age.
      Scrotal circumference, body condition score and total sperm counts of those
      animals on a high protein diet were significantly (P < 0.05) higher than those on
      a low protein diet. However, sperm motility, total dead sperm and abnormal sperm
      did not differ between the treatment groups (P < 0.05). One bull fed a high
      protein diet had significantly higher testosterone concentrations (basal and
      peak) than a bull fed low protein throughout the four sampling periods (P <
      0.05). Testosterone concentrations, scrotal circumference, volume of semen, sperm
      concentration and sperm output of bulls on low and high protein diets increased
      significantly with age (P < 0.05). Peak testosterone concentrations ranged from
      1.1 ng ml-1 at 7 months to a maximum of 5.3 ng ml-1 at 18 months. The 24 h
      secretory patterns of testosterone were episodic, pulsatile or temporal in
      nature. The peaks occurred mostly in the morning hours and ranged from one to
      five in number. Protein intake in prepubertal bulls could have significant
      influence on spermiogram and testosterone production.

PMID- 9232125
TI  - Genetic divergence of Asiatic Bdellocephala (Turbellaria, Tricladida, Paludicola)
      as revealed by partial 18S rRNA gene sequence comparisons.
AB  - Polymerase chain reaction (PCR) and direct sequencing of small ribosomal RNA
      genes were used for analysis of genetic differences among Asiatic species of
      freshwater triclad genus Bdellocephala. Representatives of four species and four
      subspecies of this genus were used to establish homology between nucleotides in
      the 5'-end portion of small ribosomal RNA gene sequences. Within 552 nucleotide
      sites of aligned sequences compared, six variable base positions were discovered,
      dividing Bdellocephala into five different genotypes. Sequence data allow to
      distinguish two groups of these genotypes. One of them unites species from
      Kamchatka and Japan, another one unites Baikalian taxa. Agreement between
      available morphological, cytological and sequence data is discussed.

PMID- 9232126
TI  - Summarizing the effects of therapy: a new table and some more terms.

PMID- 9232127
TI  - Phenylephrine and inhaled nitric oxide in adult respiratory distress syndrome.
      When are two better than one?

PMID- 9232128
TI  - Obstetric anesthesia coverage. The problem in perspective.

PMID- 9232129
TI  - Permissive hypercapnia with and without expiratory washout in patients with
      severe acute respiratory distress syndrome.
AB  - BACKGROUND: Permissive hypercapnia is a ventilatory strategy aimed at avoiding
      lung volutrauma in patients with severe acute respiratory distress syndrome
      (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that
      enhances carbon dioxide removal during mechanical ventilation by reducing dead
      space. The goal of this prospective study was to determine the efficacy of EWO in
      reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe
      ARDS treated using permissive hypercapnia. METHODS: Seven critically ill patients
      with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no
      contraindications for permissive hypercapnia were studied. On the first day,
      hemodynamic and respiratory parameters were measured and the extent of lung
      hyperdensities was assessed using computed tomography. A positive end-expiratory
      pressure equal to the opening pressure identified on the pressure-volume curve
      was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm
      H2O was reached. On the second day, after implementation of permissive
      hypercapnia, EWO was instituted at a flow of 15 l/min administered during the
      entire expiratory phase into the trachea through the proximal channel of an
      endotracheal tube using a ventilator equipped with a special flow generator.
      Cardiorespiratory parameters were studied under three conditions: permissive
      hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia.
      RESULTS: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to
      53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/-
      0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P <
      0.05). The reduction in PaCO2 was accompanied by an increase in end-inspiratory
      plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2O (P = 0.001). Expiratory washout
      also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l.min-1.m-2 (P <
      0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P <
      0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01).
      CONCLUSIONS: Expiratory washout is an effective and easy-to-use ventilatory
      modality to reduce PaCO2 and increase pH during permissive hypercapnia. However,
      it significantly increases airway pressures and lung volume through expiratory
      flow limitation, reexposing some patients to a risk of lung volutrauma if the
      extrinsic positive end-expiratory pressure is not substantially reduced.

PMID- 9232131
TI  - Assessment of cytochrome P450 3A4 activity during the menstrual cycle using
      alfentanil as a noninvasive probe.
AB  - BACKGROUND: Gender-dependent differences in cytochrome P450 activity, drug
      metabolism, drug elimination, and their clinical consequences are increasingly
      apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is
      responsible for metabolizing a vast and diverse assortment of therapeutic agents,
      including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is
      higher in women, influenced by steroid hormone levels, and is speculated to vary
      during the menstrual cycle. This investigation tested the hypothesis that P450
      3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as
      a metabolic probe for P450 3A4 activity. METHODS: Alfentanil (20 micrograms/kg
      bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age,
      26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the
      same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21
      (progesterone peak). Venous plasma alfentanil concentrations were determined by
      gas chromatography-mass spectrometry. Alfentanil clearance was determined by
      noncompartmental methods and by a three-compartment model with both pooled
      population and two-stage analysis. RESULTS: There was no significant difference
      in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD)
      were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on
      days 2, 13, and 21 of the menstrual cycle. CONCLUSIONS: Alfentanil clearances
      were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no
      change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances
      do not contribute to interindividual variability in alfentanil disposition in
      women. If other P450 3A4 substrates are comparable, then menstrual cycle
      variability in their metabolism may not be a consideration in dosing or in the
      design of pharmacokinetic investigations.

PMID- 9232130
TI  - Improvement in oxygenation by phenylephrine and nitric oxide in patients with
      adult respiratory distress syndrome.
AB  - BACKGROUND: Inhaled nitric oxide (NO), a selective vasodilator, improves
      oxygenation in many patients with adult respiratory distress syndrome (ARDS).
      Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic
      pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO,
      and their combination in patients with ARDS. METHODS: Twelve patients with ARDS
      (PaO2/FIO2 <le> 180; Murray score <me> 2) were studied. Each patient received
      three treatments in random order: intravenous phenylephrine, 50-200
      micrograms/min, titrated to a 20% increase in mean arterial blood pressure;
      inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and
      blood gas measurements were made during each treatment and at pre- and
      posttreatment baselines. RESULTS: All three treatments improved PaO2 overall. Six
      patients were "phenylephrine-responders" (delta PaO2 > 10 mmHg), and six were
      "phenylephrine-nonresponders." In phenylephrine-responders, the effect of
      phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14
      mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the
      effect of phenylephrine+NO was greater than that of either treatment alone (PaO2
      from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders,
      phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not
      statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28
      mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are
      mean +/- SEM. CONCLUSIONS: Phenylephrine alone can improve PaO2 in patients with
      ARDS. In phenylephrine-responsive patients, phenylephrine augments the
      improvement in PaO2 seen with inhaled NO. These results may reflect selective
      enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which
      complements selective vasodilation by NO.

PMID- 9232132
TI  - The role of cytochrome P450 3A4 in alfentanil clearance. Implications for
      interindividual variability in disposition and perioperative drug interactions.
AB  - BACKGROUND: There is considerable unexplained variability in alfentanil
      pharmacokinetics, particularly systemic clearance. Alfentanil is extensively
      metabolized in vivo, and thus systemic clearance depends on hepatic
      biotransformation. Cytochrome P450 3A4 was previously shown to be the predominant
      P450 isoform responsible for human liver microsomal alfentanil metabolism in
      vitro. This investigation tested the hypothesis that P450 3A4 is responsible for
      human alfentanil metabolism and clearance in vivo. METHODS: Nine healthy male
      volunteers who provided institutionally approved written informed consent were
      studied in a three-way randomized crossover design. Each subject received
      alfentanil (20 micrograms/kg given intravenously) 30 min after midazolam (1 mg
      injected intravenously) on three occasions: control; high P450 3A4 activity
      (rifampin induction); and low P450 3A4 activity (selective inhibition by
      troleandomycin). Midazolam is a validated selective in vivo probe for P450 3A4
      activity. Venous blood was sampled for 24 h and plasma concentrations of
      midazolam and alfentanil and their primary metabolites 1'-hydroxymidazolam and
      noralfentanil were measured by gas chromatography-mass spectrometry.
      Pharmacokinetic parameters were determined by two-stage analysis using both
      noncompartmental and three-compartment models. RESULTS: Plasma alfentanil
      concentration-time profiles depended significantly on P450 3A4 activity.
      Alfentanil noncompartmental clearance was 5.3 +/- 2.3, 14.6 +/- 3.8, and 1.1 +/-
      0.5 ml.kg-1.min-1, and elimination half-life was 58 +/- 13, 35 +/- 7, and 630 +/-
      374 min, respectively, in participants with normal (controls), high (rifampin),
      and low (troleandomycin) P450 3A4 activity (means +/- SD; P < 0.05 compared with
      controls). Multicompartmental modeling suggested a time-dependent inhibition
      resynthesis model for troleandomycin effects on P450 3A4 activity, characterized
      as k10(t) = k10[1-phi e-alpha(t-tzero)], where k10(t) is the apparent time
      dependent rate constant, k10 is the uninhibited rate constant, phi is the
      fraction of P450 3A4 inhibited, and alpha is the apparent P450 3A4 reactivation
      rate. Alfentanil clearance was calculated as V1 k10 for controls and men
      receiving rifampin, and as V1.average k10(t) for men receiving troleandomycin.
      This clearance was 4.9 +/- 2.1, 13.2 +/- 3.6, and 1.5 +/- 0.8 ml.kg-1.min-1,
      respectively, in controls and in men receiving rifampin or troleandomycin. There
      was a significant correlation (r = 0.97, P < 0.001) between alfentanil systemic
      clearance and P450 3A4 activity. CONCLUSIONS: Modulation of P450 3A4 activity by
      rifampin and troleandomycin significantly altered alfentanil clearance and
      disposition. These results strongly suggest that P450 3A4 is the major isoform of
      P450 responsible for clinical alfentanil metabolism and clearance. This
      observation, combined with the known population variability in P450 3A4 activity,
      provides a mechanistic explanation for the interindividual variability in
      alfentanil disposition. Furthermore, known susceptibility of human P450 3A4
      activity to induction and inhibition provides a conceptual framework for
      understanding and predicting clinical alfentanil drug interactions. Finally,
      human liver microsomal alfentanil metabolism in vitro is confirmed as an
      excellent model for human alfentanil metabolism in vivo.

PMID- 9232133
TI  - Remifentanil versus remifentanil/midazolam for ambulatory surgery during
      monitored anesthesia care.
AB  - BACKGROUND: This study was designed to define the appropriate dose of
      remifentanil hydrochloride alone or combined with midazolam to provide
      satisfactory comfort and maintain adequate respiration for a monitored anesthesia
      care setting. METHODS: One hundred fifty-nine patients scheduled for outpatient
      surgery participated in this multicenter, double-blind study. Patients were
      randomly assigned to one of two groups: remifentanil, 1 microgram/kg, given over
      30 s followed by a continuous infusion of 0.1 microgram.kg-1.min-1
      (remifentanil), remifentanil, 0.5 microgram/kg, given over 30 s followed by a
      continuous infusion of 0.05 microgram.kg-1.min-1 (remifentanil+midazolam). Five
      minutes after the start of the infusion, patients received a loading dose of
      saline placebo (remifentanil) or midazolam, 1 mg, (remifentanil+midazolam). If
      patients were not oversedated, a second dose of placebo or midazolam, 1 mg, was
      given. Remifentanil was titrated (in increments of 50% from the initial rate) to
      limit patient discomfort or pain intraoperatively, and the infusion was
      terminated at the completion of skin closure. RESULTS: At the time of the local
      anesthetic, most patients in the remifentanil and remifentanil+midazolam groups
      experienced no pain (66% and 60%, respectively) and no discomfort (66% and 65%,
      respectively). The final mean (+/-SD) remifentanil infusion rates were 0.12 +/-
      0.05 microgram.kg-1.min-1 (remifentanil) and 0.07 +/- 0.03 microgram.kg-1.min-1
      (remifentanil+midazolam). Fewer patients in the remifentanil+midazolam group
      experienced nauses compared with the remifentanil group (16% vs. 36%,
      respectively; P < 0.05). Four patients (5%) in the remifentanil group and two
      patients (2%) in the remifentanil+midazolam group experienced brief periods of
      oxygen desaturation (SpO2 < 90%) and hypoventilation (< 8 breaths/ min).
      CONCLUSIONS: Remifentanil alone or combined with midazolam provided adequate
      analgesia and maintained adequate respiration at the doses reported. The low dose
      of remifentanil combined with 2 mg midazolam, compared with remifentanil alone,
      resulted in fewer side effects, slightly greater sedation, and less anxiety.

PMID- 9232134
TI  - Transmyocardial laser revascularization induces cerebral microembolization.
AB  - BACKGROUND: Transmyocardial laser revascularization may vaporize fluid in the
      left heart, allowing bubbles to form. This study aimed to determine whether the
      laser pulse resulted in cerebral emboli and to examine changes in middle cerebral
      artery flow velocity and jugular bulb oxygen saturation (SjO2) during
      transmyocardial laser revascularization. METHODS: Twelve patients (American
      Society of Anesthesiologists physical status III) were studied after the authors
      received institutional review board approval and the patients' informed consent.
      Monitored variables included mean arterial blood pressure (measured in
      millimeters of mercury), heart rate (measured as beats/min), and partial pressure
      of carbon dioxide (measured in millimeters of mercury). A 5-MHz transesophageal
      sonography system was used to record intraventricular events after laser
      injection. Mean blood flow velocity (Vmean; measured in centimeters per second)
      was monitored in the middle cerebral artery using transcranial Doppler
      sonography, and SjO2 (expressed as a percentage) was measured using a fiberoptic
      thermodilution catheter placed in the right jugular bulb. Data were recorded
      before, during, and for 4 min after laser injection. RESULTS: After laser
      injection, intraventricular echogenic contrast was seen in transesophageal
      sonography, and 2-4 s later high-intensity signals (microemboli) appeared in the
      transcranial Doppler sonography spectra. As long as mean arterial pressure
      remained stable during the observation period, Vmean and SjO2 did not change.
      CONCLUSIONS: These data show that microemboli can be detected after laser
      injection in the middle cerebral artery, although they do not effect Vmean and
      SjO2. The results suggest that these microemboli do not induce a global oxygen
      imbalance.

PMID- 9232135
TI  - Intracuff pressures do not predict laryngopharyngeal discomfort after use of the
      laryngeal mask airway.
AB  - BACKGROUND: The laryngeal mask airway (LMA) is a large foreign body that exerts
      pressure on the pharyngeal mucosa, which may lead to throat discomfort. To
      determine whether intracuff pressures are associated with such discomfort, a
      randomized, double-blind study was performed to determine the effect of high
      versus low intracuff pressures. METHODS: Seventy healthy women were randomly
      allocated to two groups with different LMA intracuff pressures: 30 mmHg (low
      pressure) or 180 mmHg (high pressure). Pressures were controlled with a
      microprocessor-controlled monitor. Insertion of the LMA was performed by one
      investigator and facilitated with propofol and verified fiberoptically.
      Anesthesia was maintained with enflurane and nitrous oxide. The LMAs were removed
      while the patients were still asleep. Patients assessed their laryngopharyngeal
      complaints (sore throat, dysphagia, hoarseness) at 8, 24, and 48 h after
      operation on a 101-point numerical rating scale. RESULTS: No significant
      difference was found in the overall incidence of complaints between both groups
      (low pressure: 50%; high pressure: 42%). On the day of surgery, dysphagia (38%)
      was more frequent than sore throat (16%) or hoarseness (6%) (P < 0.05) within the
      high-pressure group. In the low-pressure group, the incidence of these complaints
      was not significantly different (33%, 20%, and 23%, respectively). On the
      following day, dysphagia was still present in 20% of the women in both groups,
      and other symptoms comprised 10% or less of the reported complaints. CONCLUSIONS:
      Differences in LMA intracuff pressures did not influence either the incidence or
      severity of laryngopharyngeal complaints.

PMID- 9232136
TI  - Blockade of myocardial ATP-sensitive potassium channels by ketamine.
AB  - BACKGROUND: The adenosine triphosphate (ATP)-sensitive potassium (KATP) channel
      underlies the increase in potassium permeability during hypoxia and ischemia. The
      increased outward potassium current during ischemia may be an endogenous
      cardioprotective mechanism. This study was designed to determine the effects of
      ketamine on KATP channel in rat hearts. METHODS: Inside-out and cell-attached
      configurations of patch-clamp techniques and 3 M potassium chloride-filled
      conventional microelectrodes were used to investigate the effect of ketamine on
      KATP channel currents in single rat ventricular myocytes and on the action
      potential duration of rat papillary muscles, respectively. RESULTS: Ketamine
      inhibited KATP channel activity in rat ventricular myocytes in a concentration
      dependent manner. In the inside-out patches, the concentration of ketamine for
      half-maximal inhibition and the Hill coefficient were 62.9 microM and 0.54,
      respectively. In a concentration-dependent manner, ketamine inhibited pinacidil-
      and 2,4-dinitrophenol-activated KATP channels in cell-attached patches. The
      application of ketamine to the intracellular side of membrane patches did not
      affect the conduction of single-channel currents of KATP channels. Ketamine
      increased the action potential duration, which was then shortened by pinacidil in
      a concentration-dependent manner. CONCLUSIONS: Ketamine inhibited KATP channel
      activity in a concentration-dependent manner. These results suggest that ketamine
      may attenuate the cardioprotective effects of the KATP channel during ischemia
      and reperfusion in the rat myocardium.

PMID- 9232137
TI  - Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine.
      Assessment with closed spinal window technique.
AB  - BACKGROUND: Ropivacaine produces a vasoconstriction of cutaneous vessels in
      contrast to vasodilation produced by bupivacaine. To evaluate direct spinal
      microvascular actions of these local anesthetics, the authors investigated the
      concentration-related effects of ropivacaine and bupivacaine on spinal pial
      vascular diameters using the spinal window technique. METHODS: Anesthetized dogs
      (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were
      prepared for measurement of spinal pial vessel diameters by intravital microscopy
      in a spinal window preparation. The authors administered six concentrations of
      each drug (10(-8)-10(-3) M) under the window and directly measured the spinal
      pial arteriolar and venular diameters at sequential times. Physiologic data
      including mean arterial blood pressure (MAP) and heart rate (HR) were determined
      before and after topical application of each concentration of the drugs. In
      additional experiments (n = 18), the action of topical ropivacaine and
      bupivacaine solution on spinal vessels was evaluated in the presence of
      yohimbine, prazosin, and propranolol. RESULTS: Ropivacaine significantly
      constricted whereas bupivacaine dilated pial arterioles and venules, both in a
      concentration-dependent manner. Microvascular alteration was not blocked with any
      of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each
      of which per se did not affect pial vessel diameters. Topical application of
      ropivacaine or bupivacaine did not induce any change in MAP or HR. CONCLUSIONS:
      The present results indicate that ropivacaine constricts and bupivacaine dilates
      the pial vessels of the spinal cord in a concentration-dependent fashion, and the
      mechanisms involved in such actions do not seem to be mediated via alpha- or beta
      adrenoceptor of spinal vasculature.

PMID- 9232138
TI  - Mechanoenergetics of the negative inotropism of isoflurane in the canine left
      ventricle. No O2 wasting effect.
AB  - BACKGROUND: The mechanisms underlying the negative inotropic effects of
      isoflurane are incompletely understood. One suggested mechanism is that
      isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more
      free calcium would be needed to activate contractile proteins to the same degree,
      which would impose a greater requirement for myocardial oxygen consumption used
      in the cycling of calcium. In this study, the authors use the excised, cross
      circulated, canine heart model and the volume servopump technique to measure the
      effects of isoflurane on Emax (a contractile index) and on the relationship
      between pressure-volume area (PVA, a measure of total mechanical energy) and
      myocardial oxygen consumption per beat (VO2). METHODS: Effects of intracoronary
      isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics
      were studied during isovolumic contractions. The authors measured left
      ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen
      content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0%
      isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in
      control subjects and in those receiving 2.0% isoflurane. RESULTS: Emax, PVA, and
      VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not
      change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05). CONCLUSIONS:
      These mechanoenergetic findings suggest that the primary method by which
      isoflurane decreases contractility is not by decreasing Ca2+ sensitivity of
      contractile proteins but mainly by decreasing Ca2+ handling in the excitation
      contraction coupling without myocardial oxygen wasting effect.

PMID- 9232139
TI  - Halothane attenuation of calcium sensitivity in airway smooth muscle. Mechanisms
      of action during muscarinic receptor stimulation.
AB  - BACKGROUND: In airway smooth muscle, muscarinic receptor stimulation is thought
      to increase calcium (Ca2+) sensitivity via a guanosine 5'-triphosphate (GTP)
      binding protein/protein kinase C (PKC)-mediated mechanism. This study treated the
      hypothesis that halothane reduces Ca2+ sensitivity during muscarinic receptor
      stimulation by inhibiting these second messenger pathways. METHODS: A beta-escin
      permeabilized canine tracheal smooth muscle preparation was used in which the
      cytosolic Ca2+ concentration ([Ca2+]i) is controlled and the GTP-binding protein/
      PKC pathways remain intact and can be activated. The muscarinic receptor was
      activated with acetylcholine plus GTP; the GTP-binding proteins were directly
      activated with a nonhydrolyzable form of GTP, guanosine 5'-O-(3-thiotriphosphate;
      GTP gamma S); and PKC was directly activated with the PKC agonist phorbol 12,13
      dibutyrate (PDBu). RESULTS: Free Ca2+ caused a concentration-dependent increase
      in force. Acetylcholine plus GTP significantly decreased the median effective
      concentration for free Ca2+ from 0.52 +/- 0.06 microM to 0.21 +/- 0.02 microM,
      demonstrating an increase in Ca2+ sensitivity. Halothane (0.99 +/- 0.04 mM,
      equivalent to approximately 4 minimum alveolar concentration in dogs)
      significantly attenuated this increase in Ca2+ sensitivity induced by
      acetylcholine plus GTP, increasing the median effective concentration for free
      Ca2+ from 0.21 +/- 0.02 microM to 0.31 +/- 0.03 microM. However, halothane did
      not affect the increases in Ca2+ sensitivity induced by GTP gamma S or PDBu.
      CONCLUSIONS: Halothane had no effect on increased Ca2+ sensitivity caused by
      direct activation of GTP-binding proteins with GTP gamma S or PKC with PDBu,
      suggesting that halothane attenuates acetylcholine-induced Ca2+ sensitization via
      a mechanism independent of these pathways in beta-escin-permeabilized canine
      tracheal smooth muscle.

PMID- 9232140
TI  - Positive inotropic and lusitropic effects of triiodothyronine in conscious dogs
      with pacing-induced cardiomyopathy.
AB  - BACKGROUND: The effects of triiodothyronine (T3) on systemic hemodynamics,
      myocardial contractility (preload recruitable stroke work slope; Mw), and left
      ventricular (LV) isovolumic relaxation (time constant; tau) were examined before
      and after the development of pacing-induced cardiomyopathy in conscious dogs.
      METHODS: Dogs (n = 8) were chronically instrumented for measurement of aortic and
      LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs
      received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5
      min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after
      each dose and 24 h after the final dose. Dogs were then continuously paced at 220
      240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the
      development of severe LV dysfunction, and administration of T3 was repeated.
      RESULTS: T3 produced immediate and sustained (24 h) increases (P < 0.05) in Mw
      and dP/dtmax in dogs before the initiation of pacing, consistent with a positive
      inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3
      weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure,
      decreased mean arterial and LV systolic pressures, and caused LV systolic
      (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3
      caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/-
      7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to
      57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced
      myocardial contractility and shortened LV relaxation, respectively, in the
      presence of chronic LV dysfunction. In contrast to the findings in dogs with
      normal LV function, T3 did not affect heart rate and calculated indices of
      myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3
      during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs.
      CONCLUSIONS: The findings indicate that T3 produces favorable alterations in
      hemodynamics and modest positive inotropic and lusitropic effects in conscious
      dogs with LV dysfunction produced by rapid LV pacing.

PMID- 9232141
TI  - Intrathecal alpha 2-adrenergic agonists stimulate acetylcholine and
      norepinephrine release from the spinal cord dorsal horn in sheep. An in vivo
      microdialysis study.
AB  - BACKGROUND: Intrathecal injection of clonidine and dexmedetomidine produce
      behavioral analgesia by an alpha 2-adrenergic mechanism. Functional and anatomic
      studies suggest that this analgesia is mediated by cholinergic activation. This
      hypothesis was directly tested by measuring extracellular acetylcholine
      concentrations in spinal cord interstitial fluid by means of microdialysis after
      intrathecal injection of these alpha 2-adrenergic agonists in sheep. METHODS:
      Twelve sheep with chronically implanted thoracic intrathecal catheters were
      anesthetized with halothane. Multiple 200-micron-diameter dialysis fibers were
      inserted surgically at a mid-thoracic level through the dorsal horn and perfused
      with artificial cerebrospinal fluid. After baseline sampling, either clonidine
      (100 micrograms), dexmedetomidine (100 micrograms), or saline were injected
      intrathecally. Microdialysis samples were analyzed by high-pressure liquid
      chromatography for acetylcholine and norepinephrine. RESULTS: Both alpha 2
      adrenergic agonists increased acetylcholine in microdialysate, whereas
      intrathecal saline had no effect. Analysis of the raw data showed that all groups
      differed significantly, with greater levels of acetylcholine following
      administration of dexmedetomidine than clonidine or saline. Unexpectedly,
      intrathecal clonidine also increased microdialysate norepinephrine levels.
      CONCLUSIONS: These data are consistent with previous experiments measuring
      acetylcholine concentrations in cerebrospinal fluid and support analgesia from
      alpha 2-adrenergic agonists mediated in part by cholinergic activation. In
      addition, the increase in norepinephrine concentrations after intrathecal
      administration of clonidine suggest stimulation of norepinephrine release by this
      agent.

PMID- 9232142
TI  - Actions of phenylephrine, isoproterenol, and epinephrine with halothane on
      endocardial conduction and activation in canine left ventricular papillary
      muscles.
AB  - BACKGROUND: Myocardial sensitization by halothane to the arrhythmogenic effects
      of epinephrine involves synergistic actions mediated by alpha 1- and beta
      adrenoceptors. Halothane potentiates a transient a1-adrenoceptor-mediated
      negative dromotropic effect of epinephrine on Purkinje fibers. This study
      examines how halothane alters the actions of alpha 1- and beta-agonists and
      epinephrine on endocardial conduction. METHODS: Superfused canine papillary
      muscles were mapped to locate a Purkinje-ventricular muscle junction (PVJ), and
      bipolar electrodes were placed to measure Purkinje and endocardial conduction
      velocity and PVJ conduction time during stimulation of the Purkinje layer. The
      effects of exposure to 5 microM phenylephrine, 1 microM isoproterenol, or 5
      microM epinephrine on conduction were determined in the absence and presence of
      0.4 mM halothane in three groups of 10 preparations. RESULTS: Isoproterenol
      slightly increased Purkinje conduction velocity and markedly improved conduction
      at the PVJ and in the endocardium similarly in the presence or absence of
      halothane. Phenylephrine depressed Purkinje velocity (-12%) only in the presence
      of halothane and did not slow conduction at the PVJ or in the myocardium.
      Epinephrine transiently depressed Purkinje velocity, more so with (-22%) than
      without (-12%) halothane (P < or = 0.01), and simultaneously facilitated
      conduction at the PVJ and in the myocardium. CONCLUSIONS: The prodysrhythmic
      actions of epinephrine with halothane may involve disparate effects on
      conduction, including speeding on conduction at the PVJ and in the myocardium,
      similar to that produced by isoproterenol, accompanied by simultaneous but
      transient alpha 1-mediated depression of conduction in the Purkinje system.

PMID- 9232143
TI  - Assessment of the potency and intrinsic activity of systemic versus intrathecal
      opioids in rats.
AB  - BACKGROUND: One measure of an opioid's efficacy is its ability to retain its
      analgesic effect as the intensity of a noxious stimulus is increased. A few
      studies have assessed the ability of either spinal or systemic opioids to produce
      analgesia using low- and high-intensity stimulation. There are little data
      available to show whether there are differences in efficacy between systemic and
      intrathecal opioid administration. The purpose of this study was to assess the
      relative efficacy of several clinically useful opioids systemically and spinally
      and to determine whether intrathecal administration resulted in greater efficacy
      than systemic administration. METHODS: Groups of rats were administered multiple
      doses of meperidine, morphine, hydromorphone, fentanyl, sufentanil, or
      buprenorphine either subcutaneously or intrathecally via implanted catheters.
      Noxious radiant heat was applied sequentially to each hindpaw, one at low
      intensity (adjusted to a mean withdrawal latency of 10 s) and one at high
      intensity (adjusted to a mean withdrawal latency of 5 s). Paw withdrawal
      latencies were recorded; dose-response curves for each intensity and each route
      of administration were graphically recorded, and ED50s were calculated. Ratios of
      high-to low-stimulus intensity ED50s were calculated for both routes of
      administration for each drug, and the ratios of subcutaneous-to-intrathecal ED50s
      for low-intensity stimulation were calculated to assess the relative systemic
      versus spinal potencies for each drug. RESULTS: The ratios of the high-to-low
      intensity ED50s were meperidine, 11.8, morphine, 6.1, hydromorphone, 2.6,
      fentanyl, 2.3, sufentanil, 1.8, and buprenorphine, 24.0. For intrathecal
      administration, there was uniformity of the high- to low-intensity ED50 ratios
      for the agonist drugs (meperidine, 2.1; morphine, 2.1; hydromorphone, 1.9;
      fentanyl, 1.8; sufentanil, 1.6). For morphine and hydromorphone, the systemic
      ED50 doses were several hundred times the intrathecal ED50s whereas the systemic
      to-spinal ED50 ratios for the other drugs were 20 or less. CONCLUSIONS: As
      intensity of noxious stimulation is increased, the more potent opioid agonists,
      administered systemically, produce antinociception with lesser increases in dose
      compared with lower potency drugs such as meperidine or morphine. When given
      spinally all opioid agonists tested, including morphine and meperidine,
      demonstrated good efficacy, as measured by their ability to provide
      antinociception for high versus low intensity stimulation.

PMID- 9232144
TI  - Obstetric anesthesia work force survey, 1981 versus 1992.
AB  - BACKGROUND: In 1981, with support from the American Society of Anesthesiologists
      and the American College of Obstetricians and Gynecologists, anesthesia and
      obstetric providers were surveyed to identify the personnel and methods used to
      provide obstetric anesthesia in the United States. The survey was expanded and
      repeated in 1992 with support from the same organizations. METHODS: Comments and
      questions from the American Society of Anesthesiologists Committee on Obstetrical
      Anesthesia and the American College of Obstetricians and Gynecologists Committee
      on Obstetric Practice were added to the original survey instrument to include
      newer issues while allowing comparison with data from 1981. Using the American
      Hospital Association registry of hospitals, hospitals were differentiated by
      number of births per year (stratum I, > or = 1,500 births; stratum II, 500-1,499
      births; stratum III, < 500 births) and by U.S. census region. A stratified random
      sample of hospitals was selected. Two copies of the survey were sent to the
      administrator of each hospital, one for the chief of obstetrics and one for the
      chief of anesthesiology. RESULTS: Compared with 1981 data, there was an overall
      reduction in the number of hospitals providing obstetric care (from 4,163 to
      3,545), with the decrease occurring in the smallest units (56% of stratum III
      hospitals in 1981 compared with 45% in 1992). More women received some type of
      labor analgesia and there was a 100% increase in the use of epidural analgesia.
      However, regional analgesia was unavailable in 20% of the smallest hospitals.
      Spinal analgesia for labor was used in 4% of parturients. In 1981, obstetricians
      provided 30% of epidural analgesia for labor; they provided only 2% in 1992.
      Regional anesthesia was used for 78-85% (depending on strata) of patients
      undergoing cesarean section, resulting in a marked decrease in the use of general
      anesthesia. Anesthesia for cesarean section was provided by nurse anesthetists
      without the medical direction of an anesthesiologist in only 4% of stratum I
      hospitals but in 59% of stratum III hospitals. Anesthesia personnel provided
      neonatal resuscitation in 10% of cesarean deliveries compared with 23% in 1981.
      CONCLUSIONS: Compared with 1981, analgesia is more often used by parturients
      during labor, and general anesthesia is used less often in patients having
      cesarean section deliveries. In the smallest hospitals, regional analgesia for
      labor is still unavailable to many parturients, and more than one half of
      anesthetics for cesarean section are provided by nurse anesthetists without
      medical direction by an anesthesiologist. Obstetricians are less likely to
      personally provide epidural analgesia for their patients. Anesthesia personnel
      are less involved in newborn resuscitation.

PMID- 9232145
TI  - The effect of electronic record keeping and transesophageal echocardiography on
      task distribution, workload, and vigilance during cardiac anesthesia.
AB  - BACKGROUND: Electronic anesthesia record keeping (EARK) systems increasingly are
      used in the operating room, but studies have only recently begun to investigate
      their effect on anesthesia task performance. Teak analysis, workload assessment,
      and vigilance assessment techniques were used to study senior residents providing
      anesthesia for coronary artery bypass graft (CABG) procedures. The impact on
      anesthesia residents' workload of the routine use of transesophageal
      echocardiography (TEE) also was examined. METHODS: Before each case, the record
      keeping system was randomly selected as either electronic (Distek ARKIVE; EARK)
      or traditional manual recording (MAN). Twenty CABG procedures (10 EARK and 10
      MAN) were examined, with observation commencing with anesthetic induction and
      terminating on initiation of cardiopulmonary bypass. The activities of each
      resident, divided into 32 task categories (e.g., "laryngoscopy," "observe
      monitors," etc.), were recorded by a trained observer using a computer. The
      response latency to a randomly activated alarm light was used as a measure of
      vigilance ("vigilance latency"). Workload was rated by subject and observer at
      random 10- to 15-min intervals throughout the case. Data analysis included
      calculation of workload density (number of tasks/min multiplied by task-specific
      workload values) and task-links (relationship between sequential tasks). RESULTS:
      The two groups had a similar distribution of tasks before intubation. In only 4
      of the 20 cases studied did any manual record keeping occur before intubation.
      After intubation, the EARK group spent less time record keeping and using the TEE
      but more time observing the monitors and conversing with the attending physician
      than the MAN group did. All subjects reported significantly higher workload
      scores before intubation compared with after intubation. Similarly, vigilance
      latency was greater before intubation compared with after intubation (57 vs. 31
      s; P < 0.001). There were no significant differences between the two record
      keeping groups in subjective workload scores, workload density, or vigilance
      latency. During TEE use, vigilance latency was significantly longer, and workload
      density was greater than during other monitoring or recording tasks. CONCLUSIONS:
      This study provides an objective description of the task distribution and
      workload during the administration of anesthesia for cardiac surgery. Under the
      conditions of this study. EARK use modestly decreased the time spent record
      keeping during the postintubation prebypass period. However, there was no effect
      of EARK either on vigilance or several measures of workload. TEE use was
      associated with increased workload and possibly decreased vigilance.

PMID- 9232146
TI  - An algorithm for assessing intraoperative mean arterial pressure lability.
AB  - BACKGROUND: Intraoperative blood pressure lability may be related to risk
      factors, hypovolemia, light anesthesia, and morbid outcomes, but the measurements
      of lability in previous studies have been limited by imprecise and infrequent
      data collection methods. Computerized intraoperative data acquisition systems
      have provided an opportunity to readdress the issue of intraoperative blood
      pressure lability with more abundant and precise data. This study sought to
      derive and validate an algorithm (expert system) to measure mean arterial
      pressure (MAP) lability. METHODS: Two hundred thirty-nine computerized anesthesis
      records were reviewed retrospectively. Three anesthesiologists separately rated
      MAP as very stable, average, or very labile. The parameters of a computer
      algorithm that measured the change of median MAP between consecutive 2-min epochs
      were optimized to achieve the best possible agreement among the
      anesthesiologists. The algorithm was then validated on 229 additional anesthesia
      records. RESULTS: The proportion of consecutive 2-min epochs in which the
      absolute value of the fractional change of median MAP exceeded 0.06 (i.e., 6%)
      correlated strongly with the anesthesiologists' ratings (r = 0.78; P < 0.0001).
      The optimal sensitivity and specificity of the algorithm for detecting MAP
      lability were 98% and 59%, respectively. CONCLUSIONS: One potential application
      of expert systems to anesthesia practice is a "smart alarm" to detect blood
      pressure lability. It may also provide a better tool to assess the relation
      between lability and outcome than has been available previously.

PMID- 9232147
TI  - Whole lung torsion after a thoracoabdominal esophagogastrectomy.

PMID- 9232148
TI  - Intraoperative diagnosis of torsion of the left lung after repair of a disruption
      of the descending thoracic aorta.

PMID- 9232149
TI  - Severe maternal hypotension and fetal bradycardia after a combined spinal
      epidural anesthetic.

PMID- 9232150
TI  - Combined spinal and epidural anesthesia in a parturient with idiopathic
      hypertrophic subaortic stenosis.

PMID- 9232151
TI  - Maternal respiratory arrests, severe hypotension, and fetal distress after
      administration of intrathecal, sufentanil, and bupivacaine after intravenous
      fentanyl.

PMID- 9232152
TI  - Usable versus overall tracheal tube length: the difference may be critical.

PMID- 9232153
TI  - Response to "Ethical concerns in anesthetic care for patients with do-not
      resusitate orders".

PMID- 9232154
TI  - Response to "Ethical concerns in anesthetic care for patients with do-not
      resuscitate orders".

PMID- 9232155
TI  - Response to "Ethical concerns in anesthetic care for patients with do-not
      resuscitate orders".

PMID- 9232156
TI  - Do culture results tell us anything about the risk of infection with spinal
      catheters?

PMID- 9232157
TI  - Failure to ventilate due to glass ampule fragment occlusion of the breathing
      circuit.

PMID- 9232158
TI  - Does early extubation ("fast-tracking") of coronary artery bypass graft surgery
      patients truly decrease perioperative costs?: Appropriate analysis of direct
      variable costs.

PMID- 9232159
TI  - Oxygen insufflation through the fiberscope to assist intubation is not
      recommended.

PMID- 9232160
TI  - Kinking of the proximal end of a nasal RAE tube after intubation via laryngeal
      mask airway: an alternative stabilization approach.

PMID- 9232161
TI  - Laryngotracheal lidocaine administration.

PMID- 9232163
TI  - Oversize endotracheal tubes and intubation via laryngeal mask airway.

PMID- 9232162
TI  - Hybrid intravenous infusion connections and potential flow reduction.

PMID- 9232164
TI  - Sex hormones and vascular reactivity.
AB  - It is increasingly recognized that sex steroids have, among many other effects,
      the ability to cause vasodilation. The vasodilatory effects of estradiol have
      been the best documented and described. At low concentrations, estradiol has the
      ability to improve impaired endothelium dependent (nitric oxide mediated)
      relaxation in estrogen deficient subjects. At high concentrations, estradiol
      causes vasodilation principally by endothelium independent mechanisms, in a
      gender independent fashion, which appear to involve a number of pathways such as
      ATP-dependent K+ channels. Testosterone also has ability, at higher doses, to
      cause vasodilation of the coronary circulation, in a gender independent fashion.
      The mechanisms of sex steroid-induced vasodilation are reviewed in this article.

PMID- 9232167
TI  - Selective coronary artery perfusion in vitro: a method to study cardiac effects
      of contrast media.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated selective perfusion of the
      coronary arteries in the isolated rat heart as a model for studying contrast
      medium-induced cardiac effects and compared the effects of iodixanol, iotrolan,
      and ioxaglate with this model. MATERIALS AND METHODS: Isolated, spontaneously
      beating rat hearts were used. Control hearts were perfused in the Langendorff or
      the selective perfusion mode receiving Krebs Henseleit buffer. Contrast media
      were injected selectively into the left coronary artery. Left ventricular
      pressure and electrocardiographic parameters were monitored continuously
      throughout the experiments. RESULTS: The stability of the selective perfusion
      preparation was similar to that of the conventional Langendorff preparation.
      Ioxaglate (0.3 g iodine per kilogram body weight) significantly (P < .05)
      depressed left ventricular contractility and decreased (P < .05) left ventricular
      pressure. Iodixanol and iotrolan had minor cardiac effects. CONCLUSION: Selective
      coronary artery perfusion seems to be a suitable model for studying direct
      cardiac effects of contrast media. The nonionic dimers, iodixanol and iotrolan,
      induce only minor changes in cardiac function.

PMID- 9232166
TI  - MR and conventional angiography: work in progress toward assessing utility in
      radiology.
AB  - RATIONALE AND OBJECTIVES: The authors assessed health-related quality of life
      changes associated with peripheral x-ray angiography and magnetic resonance (MR)
      angiography. MATERIALS AND METHODS: Utility (the desirability or preference that
      individuals exhibit for a particular health state) was assessed in 30 patients
      with peripheral vascular disease referred for angiography by using a rating
      scale, additional categoric scaling questions to separate preference from
      experience, a willingness-to-pay technique, functional and cognitive status
      questions, and a time trade-off technique. All patients underwent both MR
      angiography and x-ray angiography. RESULTS: Patients reported significantly (P <
      .05) less anxiety after the test, less pain after the test, fewer new physical
      limitations, and less effect on performance of daily activities with MR
      angiography. Findings from the overall rating scale and categoric scaling
      questions also significantly (P < .05) favored MR angiography. Patients were
      willing to pay a mean of 2.12% of annual income to avoid MR angiography and a
      mean of 7.41% to avoid x-ray angiography. The median quality-adjusted life gain
      required by patients to undergo the procedures was 52.5-60 days for x-ray
      angiography and 10.5 days for MR angiography, without discounting. CONCLUSION: X
      ray angiography has more profound short-term adverse effects on life than does MR
      angiography. Preference-based measures can be adapted to elicit patient values
      for short-term health states as seen in radiology.

PMID- 9232165
TI  - The physiology and pathophysiology of the nitric oxide/superoxide system.
AB  - The endothelium modulates vascular tone by producing vasodilator vasoconstrictor
      substances. Of these, the most well characterized and potentially important are
      .NO and .02-. These small molecules exhibit opposing effects on vascular tone,
      and chemically react with each other in a fashion which negates their individual
      effects and leads to the production of potentially toxic substances. These
      dynamic interactions may likely have important implications, altering not only
      tissue perfusion but also contributing to the process of atherosclerosis. .NO is
      produced in endothelial cells by an enzyme termed nitric oxide synthase. The
      endothelial .NO-synthase is activated when the intracellular level of calcium is
      increased. This occurs in response to neurohormonal stimuli and in response to
      shear stress. Acetylcholine and substance P are examples of neurohumoral
      substances that are able to stimulate the release of nitric oxide and to assess
      endothelial regulation of vasomotor tone. Importantly, the vasodilator potency of
      nitric oxide released by the endothelium is abnormal in a variety of diseased
      states such as hypercholesterolemia, atherosclerosis and diabetes mellitus. This
      may be secondary to decreased synthesis of nitric oxide or increased degradation
      of nitric oxide due to superoxide anions. More recent experimental observations
      demonstrate increased production of superoxide in atherosclerosis, diabetes
      mellitus and high renin hypertension suggesting that endothelial dysfunction in
      these states is rather secondary to increased .NO metabolism rather than due to
      decreased synthesis of .NO. Superoxide rapidly reacts with nitric oxide to form
      the highly reactive intermediate peroxynitrite (ONOO-). Peroxynitrite can be
      protonated to form peroxynitrous acid which in turn can yield the hydroxyl
      radical (OH.). These reactive species can oxidize lipids, damage cell membranes,
      and oxidize thiol groups. .NO given locally, exerts potent antiatherosclerotic
      effects such as inhibition of platelet aggregation, inhibition of adhesion of
      leukocytes and the expression of leukocyte adhesion molecules. It is important to
      note, however, that in-vivo treatment with .NO (via organic nitrates) increases
      rather than decreases oxidant load within endothelial cells. It remains therefore
      questionable whether systemic treatment with .NO may have antiatherosclerotic
      properties or whether .NO may initiate or even accelerate the atherosclerotic
      process.

PMID- 9232168
TI  - Teleradiology consultation for a rural hospital: patterns of use.
AB  - RATIONALE AND OBJECTIVES: The authors documented quantitatively how teleradiology
      was used for contemporaneous consultation with a radiologist by physicians at a
      small rural hospital. MATERIALS AND METHODS: The authors collected 31/2 years
      worth of data at a small hospital on all patients (n = 327) for whom a
      radiologist's consultation by teleradiology was requested and compared the data
      with those from a control group of 309 patients whose studies were interpreted at
      the same hospital. RESULTS: Teleradiology consultation was requested by the
      attending physician in 3.6% (519 of 14,586) of all examinations performed during
      the study period. Physicians requested teleradiology consultation most often for
      patients with multiple examinations (average 1.59 vs 1.35 for controls).
      Examinations of infants were 10 times more prevalent in the teleradiology group
      than in the control group. The indication for most (52%) teleradiology
      consultations was trauma. Requests for interpretation of spine and abdominal
      radiographs were relatively more frequent than were those of other studies.
      CONCLUSION: Physicians in this rural practice used contemporaneous radiologic
      consultation for selected specific examinations, with emphasis on examinations
      for trauma, spine, abdomen, and the infant age group.

PMID- 9232169
TI  - Adequacy testing of training set sample sizes in the development of a computer
      assisted diagnosis scheme.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the performance changes of a
      computer-assisted diagnosis (CAD) scheme as a function of the number of regions
      used for training (rule-setting). MATERIALS AND METHODS: One hundred twenty
      regions depicting actual masses and 400 suspicious but actually negative regions
      were selected as a testing data set from a database of 2,146 regions identified
      as suspicious on 618 mammograms. An artificial neural network using 24 and 16
      region-based features as input neurons was applied to classify the regions as
      positive or negative for the presence of a mass. CAD scheme performance was
      evaluated on the testing data set as the number of regions used for training
      increased from 60 to 496. RESULTS: As the number of regions in the training sets
      increased, the results decreased and plateaued beyond a sample size of
      approximately 200 regions. Performance with the testing data set continued to
      improve as the training data set increased in size. CONCLUSION: A trend in a
      system's performance as a function of training set size can be used to assess
      adequacy of the training data set in the development of a CAD scheme.

PMID- 9232170
TI  - Assessment of respiration during video fluoroscopy of dysphagic patients.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the coordination of swallowing
      and respiration in dysphagic patients. MATERIALS AND METHODS: Video fluoroscopy
      and respirometry were performed simultaneously during 98 swallows in 33 patients
      (18 women, 15 men) with a median age of 70 years (interquartile range, 52-78
      years). Pharyngeal transit time, deglutition apnea, and the ratio between the two
      (swallowing safety index) were calculated. Presence of a misdirected swallow
      (aspiration or penetration) was indicated. RESULTS: Pharyngeal transit time was
      not associated with deglutition apnea. Misdirected swallow was associated with a
      slightly prolonged pharyngeal transit time, a slightly shorter deglutition apnea,
      and a significantly lower swallowing safety index (1.8 [1.0-4.2] vs 4.5 [2.4
      6.7]; P < .001) compared with normally directed swallow. The association between
      misdirected swallow and lower swallowing safety index was independent of
      pharyngeal transit time. CONCLUSION: Assessment of respiration is important in
      the evaluation of dysphagia. Aspiration, especially in elderly dysphagic
      patients, may be a consequence of primarily disturbed respiration. A low
      swallowing safety index may indicate risk of misdirected swallow.

PMID- 9232171
TI  - Interactive MR-guided, 14-gauge core-needle biopsy of enhancing lesions in a
      breast phantom mode.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to determine the accuracy of
      magnetic resonance (MR) imaging-guided core-needle biopsy performed with a
      titanium biopsy needle in a breast phantom. MATERIALS AND METHODS: Eight 6-7-mm
      lesions were created at random positions in a lard breast phantom. Each 0.2-mL
      lesion contained 0.118 mg of gadopentetate dimeglumine, 0.0025 mL of methylene
      blue dye, and 23.8 mg of gelatin. Rapid fast spin-echo MR imaging was used to
      guide placement of a 14-gauge titanium core-biopsy needle. A 1.5-T MR imager was
      used with an open-platform phased-array breast coil. RESULTS: Visualization of
      blue dye in core specimens confirmed successful biopsy in 16 of 16 attempts. One
      (n = 13) or two (n = 3) passes through the "skin" of the phantom were necessary
      for biopsy. The needle trajectory was adjusted less than three times for each
      pass through the "skin" in 15 of 16 biopsies. Cores that contained lesion
      material were obtained in the first sample in 15 of 16 biopsies. On T1-weighted
      images, needles cast 7-mm-diameter artifacts. CONCLUSION: MR imaging can be used
      accurately to guide core-needle biopsy of 6-7-mm lesions in a breast phantom.

PMID- 9232173
TI  - Recognizing and managing residents' problems and problem residents.

PMID- 9232172
TI  - Adjustable temporary venous spring filter: in vitro assessment.
AB  - RATIONALE AND OBJECTIVES: The authors performed an in vitro study to evaluate a
      temporary venous spring filter that can extend vessels of a wide range of
      diameters to a slit-shaped canal. MATERIALS AND METHODS: Filters were placed in
      thin polyethylene tubes or in porcine inferior vena cava specimens (diameter,
      10.0-16.0 mm). Physiologic saline was substituted for blood flow, and blood clots
      of three sizes (6 x 10, 6 x 20, and 9 x 20 mm) were funneled to the filter. Clot
      trapping ability was assessed by the degree of luminal extension. RESULTS: When
      the luminal extension was increased from 2.6r to 2.8r (where r is the original
      radius of the vein models), clot-trapping ability increased significantly (61.1%
      87.5% in polyethylene tubes and 15.8%-77.5% in venous specimens, P < .001). When
      the luminal extension was increased to 3.0r, more than 90% of the clots were
      trapped in all tubes. After trapping the small, medium, and large clots, mean
      intraluminal pressure elevation was 1.0, 1.0, and 17.0 cm of saline,
      respectively. CONCLUSION: Despite its simple design, the spring filter proved to
      be an efficient filtering device.

PMID- 9232175
TI  - International medical graduates.

PMID- 9232174
TI  - Radiologic education of pediatric residents during morning report.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the radiologic educational content
      of a pediatric morning report teaching conference to determine ways of improving
      radiologic education of pediatric residents. MATERIALS AND METHODS: The authors
      conducted a prospective, observational study from September 1995 to June 1996.
      Data collected from conference case presentations included types of radiologic
      studies shown and unanswered radiologic questions. RESULTS: During 388 case
      presentations, 559 radiologic studies were shown. Imaging modalities most
      commonly shown were plain radiography, computed tomography (CT), and ultrasound.
      The most common types of images shown were chest and abdominal plain radiographs
      and head CT scans. Common unanswered questions concerned radiologic study
      indications and techniques and radiologic appearance of diseases. CONCLUSION:
      Pediatric residents must learn basic radiologic interpretation methods, imaging
      approaches to common problems, and ways of using the radiologist as a consultant.
      A large part of their radiologic education occurs in morning report, from
      nonradiologists. Participating in a morning report is an important way for
      radiologists to enhance the education of primary care residents.

PMID- 9232176
TI  - Myxoid tissue: its morphology, histochemistry, and relationship with other
      supporting tissues.
AB  - Myxoid tissue was studied in the supporting organ of the cat epiglottis
      ("epiglottic cartilage"). Under the light microscope, myxoid tissue was
      characterized by stellate cells placed into an avascular acidic extracellular
      matrix. This extracellular matrix was alcianophilic at pH = 2.5, reacting with
      the colloidal iron stain, and staining metachromatically with toluidine blue O at
      pH = 5.0. Treatment of sections with testicular hyaluronidase abolished these
      reactions. In addition, staining persisted after methylation/saponification
      pretreatment, indicating hyaluronic acid as the main acidic component of myxoid
      extracellular matrix. Under the electron microscope, myxoid extracellular matrix
      formed flocculent electron dense precipitates. Stellate myxoid cells were
      characterized by bundles of intermediate (8 nm) cytoplasmic filaments. Myxoid
      cells were devoid of a basal lamina, contained a few small lipid droplets, and
      stored some glycogen. Bundles of collagen fibrils, 80-120 nm in diameter, were
      seen in myxoid areas. Myxoid cells reacted to S-100 protein, glial fibrillary
      acidic protein, and neuron specific enolase. Moreover, in adult animals, myxoid
      cells stained for neurofilament protein 200. All these markers were also present
      in chondrocytes of elastic and fibrous cartilage, indicating a close relationship
      between myxoid cells and chondrocytes. This was supported by the observation of
      continuous transitional forms of myxoid tissue into elastic or fibrous cartilage.
      In 8-week-old kittens, the supporting organ of the epiglottis was found mainly to
      consist of myxoid tissue with only a few interspersed islets of chondrocytes. It
      is therefore concluded that myxoid tissue can serve as a precursor of cartilage.

PMID- 9232177
TI  - Cationic colloidal gold staining of acidic glycoconjugates in mouse Paneth cells.
AB  - The acidic glycoconjugates of mouse ileum Paneth cells were examined with the aid
      of light and electron microscopy, using cationic colloidal gold (CCG) as a probe.
      Specimens of mouse ilea were fixed in half-strength Karnovsky's fixative and
      embedded in Lowicryl K4M resin. Semithin and ultrathin sections were cut of
      examination with light and electron microscopy, respectively. Examination of the
      sections using light microscopy revealed the positive staining of CCG at pH 1.0
      and pH 2.5, which was detected at the rim of secretory granules and at the
      supranuclear regions of the Paneth cells. At pH 4.0, in addition to staining of
      the secretory granule rim, weak staining was observed in the granule core. At pH
      7.2, the cytoplasm other than secretory granules exhibited positive CCG staining.
      Examination of the sections using electron microscopy, at pH 1.0, the trans
      lamellae of the Golgi apparatus, the rim of the secretory granules, and lysosomes
      were labeled selectively by CCG. At pH 2.5, labeling was also discernible over
      the same structures in the cells. However, at this pH, the labeling intensity was
      stronger than that at pH 1.0, due to the dual labeling of sulfated and sialylated
      glycoconjugates in these structures. At pH 4.0, the Golgi apparatus, rims and
      cores of secretory granules and ribosomes were labeled. Lysosomes and nuclei were
      also positively stained. At pH 7.2, the rims of secretory granules were not
      stained. The present results indicate that the CCG method gives good resolution
      and contrast when applied to staining, and therefore is useful for the specific
      staining of glycoconjugates such as sulfated, sialylated and phosphated
      glycoconjugates for light and electron microscopy.

PMID- 9232178
TI  - Analysis of apoptosis morphology in Epstein-Barr virus positive and negative
      Burkitt's lymphoma cells.
AB  - In recent studies of cycloheximide (CHX)-induced apoptosis in sublines of
      established Burkitt's lymphoma cell lines (BJA-B) both with and without Epstein
      Barr virus (EBV) infection, we noticed two distinct types of apoptosis
      morphology. In the present paper, we have classified these, and further carried
      out a statistical analysis of their incidence in untreated and CHX-treated EBV
      free (EBV(-)) and EBV-infected (EBV(+)) BJA-B cells. CLASSIFICATION: Both types
      of apoptosis morphology demonstrated typical nuclear and cytoplasmic
      condensation. However, "Type 1 apoptotic cells" (AP1) maintained a spherical or
      ovoid shape, but "Type 2 apoptotic cells" (AP2) were typified by the lobulation
      of their nuclear and cytoplasmic structures to form "clover leaf" shapes.
      Statistical analysis of incidence: The numbers of AP1 and AP2 cells were analysed
      using a chi 2 test, with results as follows: EBV(-) cells underwent AP1 in
      preference to AP2 (90.5% versus 9.5%) (p < 0.001), whilst EBV(+) cells had
      comparably more AP2, making AP1 and AP2 approximately equal (49.3% versus 50.7%)
      (p > 0.1). In EBV(-) cells, treatment with CHX had little effect on the ratios of
      differing apoptotic morphology. In contrast, in the EBV(+) cells, cell death was
      altered from AP2 (50.7%-->25.2%) towards AP1(49.3%-->74.8%) (p < 0.001). We
      propose that cellular proteins known to be associated with EBV infection not only
      protect the cells from apoptosis, but also affect the phenotype of apoptosis.
      This knowledge may be useful for defining possible mechanisms of apoptosis
      induction and/or inhibition in specific models.

PMID- 9232179
TI  - Immunocytochemical localization of taurine in the pineal organ and retina of an
      anadromous fish, Plecoglossus altivelis.
AB  - Light and electron microscopic immunolocalization of taurine, a sulfur-containing
      free amino acid, was investigated in the photoneuroendocrine pineal organ and the
      retinal photoreceptor and pigment epithelial layer of the ayu Plecoglossus
      altivelis, an anadromous fish. Intense immunostaining was found in the outer
      segments of pineal photoreceptors and retinal cone-like cells. Moderate but
      definite immunostaining was found in the cytoplasmic processes of pineal
      supporting cells, the outer segments of retinal rod-like cells, and the apical
      processes of pigment epithelial cells. Although the electron microscopic
      immunogold labeling was not completely coincident with the results of light
      microscopic immunostaining, concentrated immunogold particles appeared in the
      inner segments of photoreceptor cells, the cytoplasmic processes of pineal
      supporting cells, and the apical processes of pigment epithelial cells. These
      light and electron microscopic findings in taurine immunolocalization were
      discussed in relation to the functions of taurine known mainly from retinal
      physiology. It was suggested that the abundant taurine localization may be
      involved at least in the protection of photoreceptor outer segments against
      harmful factors, and in the transportation of nutrients and metabolites. The
      immunostaining for taurine is useful for the discrimination of different types of
      photoreceptor cells in the pineal organ and retina of fish.

PMID- 9232180
TI  - Suppression by platelet factor 4 of the myogenic activity of basic fibroblast
      growth factor.
AB  - The effect of platelet factor 4 (PF4) on myoblast cultures with or without basic
      fibroblast growth factor (bFGF) or other growth factors was investigated in the
      present in vitro experiments, with reference to bFGF binding to myoblast membrane
      fraction. When PF4 was added to the culture medium 1 day after myoblast
      cultivation, the nuclei of both myoblasts and myotubes were markedly reduced in
      number in a dose-dependent manner, whereas the inhibitory effect of PF4 on
      myoblast development was not observed when PF4 was added to the culture medium 3,
      7, or 14 days after myoblast cultivation. In contrast, bFGF significantly
      increased the numbers of myoblast and myotube nuclei. When bFGF and PF4 were
      simultaneously added to the culture medium, PF4 abolished the facilitatory
      effects of bFGF on myogenesis. The real-time biospecific interaction analysis
      (BLA) core system showed that the myoblast membrane fraction at 1 day after
      cultivation contains bFGF-binding elements which are blocked by PF4 in a dose
      dependent manner. Moreover, [126I]-bFGF binding experiments indicated the
      existence of both high and low affinity binding sites on myoblast membranes,
      although the high affinity binding sites decreased in number and the dissociation
      constant increased in value as the culture period was prolonged. Among the six
      other growth factors examined, acidic fibroblast growth factor and platelet
      derived growth factor-BB stimulated myogenesis, and their effects were blocked by
      PF4 treatment. These findings suggest that: 1) PF4 inhibits myoblast
      proliferation and myotube formation only for a limited initial period of
      cultivation, possibly because of the time-dependent down-regulation of high
      affinity bFGF receptors: and 2) PF4 may be used as a tool to investigate the
      function of endogenous heparin-binding growth factors upregulated transiently at
      a certain developmental stage or in case of tissue damage and repair, even though
      it is not monospecific to bFGF.

PMID- 9232181
TI  - Elimination of apoptotic granulosa cells by intact granulosa cells and
      macrophages in atretic mature follicles of the guinea pig ovary.
AB  - Phagocytic cells disposing of dying granulosa cells in the atretic ovarian
      follicles were morphologically studied in guinea pig ovaries at various stages of
      estrous cycle. Epon embedded semithin sections stained with toluidine blue were
      observed with a light microscope, and ultrathin sections were examined under a
      transmission electron microscope. Frozen sections were processed for acid
      phosphatase histochemistry and MR-1 (a monoclonal antibody against guinea pig
      macrophages) immunohistochemistry. In animals during the estrus period (days 1
      and 2) as well as the second half of the estrous cycle (days 11 and 16), there
      were numerous mature follicles in which massive groups of granulosa cells were
      undergoing apoptosis. Two kinds of phagocytic cells were identified in these
      follicles of the initial stage of atresia: one was intact granulosa cells
      ingesting neighboring dead granulosa cells, and the other was large round cells
      identified as macrophages due to their strong acid phosphatase activity and MR-1
      immunoreactivity. Mature follicles of the advanced stage of atresia were
      frequently recognized during the metestrus period (days 4 and 5). Small stellate
      cells were regarded as surviving granulosa cells, while large round cells showing
      intense reactions for acid phosphatase and MR-1 were identified as macrophages.
      This study demonstrates that both intact granulosa cells and macrophages
      participate in the elimination of apoptotic granulosa cells in atretic mature
      follicles of the guinea pig ovary, and remain even in the advanced stages of
      atresia.

PMID- 9232182
TI  - Developmental changes in mucous cells of the early postnatal rat parotid gland:
      an ultrastructural and histochemical study.
AB  - Previous studies on the development of the parotid gland in various mammals have
      demonstrated that terminal clusters and acini contain mucous cells during the
      early postnatal period. However, little information has been available concerning
      the exact fate of the secretory granules in the mucous cells, specifically as to
      whether or not the mucous cells differentiate into serous cells. The present
      study aimed to determine the time of appearance of the mucous cells in the rat
      parotid gland as well as the morphological and histochemical changes of their
      granules. Light microscopy showed that cells positively stained with periodic
      acid Schiff and alcian blue were sparsely distributed in the terminal clusters
      and acini on day 1 but had multiplied to a maximal level by day 5. They decreased
      in number on day 8 and were not recognizable at all by day 10. Electron
      microscopy revealed that the mucous cells initially contained granules of
      homogeneous low electron density, and then bipartite and tripartite granules with
      electron-dense cores were detected. By day 8 granules showing bipartite and
      tripartite structures and granules of homogeneous high electron density were seen
      to coexist in single cells. These observations suggest that mucous cells exist in
      parotid glands for a limited period of time and that, as the gland develops, the
      mucous granules come to resemble serous granules. Lectin histochemistry indicated
      that the secretory granules in the mucous cells were positive for peanut
      agglutinin, soybean agglutinin and wheat germ agglutinin, suggesting the
      occurrence of beta -D-galactose, alpha -D-N-acetyl galactosamine and beta -D-N
      acetyl glucosamine which are the same sugar residues as those found in the
      granules of mature parotid serous cells. Immunostaining showed that even the low
      electron-dense granules in the mucous cells were weakly reactive for anti-rat
      parotid gland amylase; this reactivity gradually increased with development.
      These results suggest that mucous cell secretory granules which contain abundant
      glycoconjugate for a limited period during the development of the gland may
      change into serous granules.

PMID- 9232183
TI  - Detection of mineral density on the surface of mouse parietal bones:
      backscattered electron imaging of low accelerating voltage scanning electron
      microscopy.
AB  - Backscattered electron (BSE) imaging of scanning electron microscopy (SEM) was
      applied to a study on the mineral density of the bone surface. The neonatal and
      adult mouse parietal bones freed of the periosteum and covering cells were
      examined in a field emission scanning electron microscope equipped with a high
      sensitivity BSE detector at 1-30 kV accelerating voltages. The mineral density of
      the bone surface was observable in BSE images at 5 kV accelerating voltage while
      only the topographic structures of the surface were obtained under an
      accelerating voltage less than 5 kV. As the accelerating voltages increased from
      5 kV, the bright areas were extended, probably due to the imaging of the
      calcified bone matrix under the uncalcified osteoid. The bone surface is usually
      divided into smooth and rough areas according to its irregularities. BSE images
      at 5 kV clearly showed that the smooth areas were further divided into dark and
      bright areas which apparently corresponded to the uncalcified osteoid and
      calcified bone matrix, respectively. Bright granules, about 1.0-3.0 microns in
      diameter, were sometimes observed at the border between the osteoid and calcified
      bone matrix; these granular calcified areas were regarded as the calcifying front
      forming the calcified bone matrix from the osteoid. The present study
      demonstrated that the distribution of the osteoid on the mouse parietal bone
      surface changes depending on age: the osteoid occupied a large area in the
      parietal bone surface in neonatal mice, but was small in adult mice. Thus, low
      accelerating voltage SEM using BSE provides new information on the distribution
      of the osteoid and the bone matrix calcification under both normal and
      pathological conditions.

PMID- 9232185
TI  - Model-based diagnosis in medicine.

PMID- 9232186
TI  - Abstract temporal diagnosis in medical domains.
AB  - Most current model-based diagnosis formalisms and algorithms are defined only for
      static systems, which is often inadequate for medical reasoning. In this paper we
      describe a model-based framework plus algorithms for diagnosing time-dependent
      systems where we can define qualitative temporal scenarios. Complex temporal
      behavior is described within a logical framework extended by qualitative temporal
      constraints. Abstract observations aggregate from observations at time points to
      assumptions over time intervals. These concepts provide a very natural
      representation and make diagnosis independent of the number of actual
      observations and the temporal resolution. The concept of abstract temporal
      diagnosis captures in a natural way the kind of indefinite temporal knowledge
      which is frequently available in medical diagnoses. We use viral hepatitis B
      (including a set of real hepatitis B data) to illustrate and evaluate our
      framework. The comparison of our results with the results of HEPAXPERT-I is
      promising. The diagnosis computed in our system is often more precise than the
      diagnosis in HEPAXPERT-I and we detect inconsistent data sequences which cannot
      be detected in the latter system.

PMID- 9232184
TI  - An immuno- and enzyme cytochemical study of the H(+)-K+ ATPase in human parietal
      cells after administration of tetragastrin and omeprazole.
AB  - The presence of subunit proteins, 1H9 for the alpha-subunit and 2B6 for the beta
      subunit, of H(+)-K+ ATPase and its activity in tubulovesicles and intracellular
      canaliculi of gastric parietal cells were immunocytochemically and enzyme
      cytochemically examined. Specimens were taken from healthy human volunteers by
      endoscopic biopsy in resting, tetragastrin-stimulated and omeprazole-inhibited
      conditions. H(+)-K+ ATPase was present in both intracellular canaliculi and
      tubulovesicles in these three conditions. Gold particles of the alpha-subunit
      decreased in number, and those showing the beta-subunit increased under both
      gastrin-stimulating and omeprazole-inhibiting conditions compared with parietal
      cells in the resting state. We suggest that the administration of tetragastrin
      and omeprazole alter the turnover rate of each subunit of H(+)-K+ ATPase,
      resulting in the difference of the proportions of alpha- and beta-subunits.
      Moreover, the activity of H(+)-K+ ATPase was detected strongly beneath the
      membrane of microvilli and weakly in that of tubulovesicles under these three
      conditions. After 7 days of daily oral omeprazole intake, H(+)-K+ ATPase in
      parietal cells were detected in intracellular canaliculi and tubulovesicles.
      However, the H(+)-K+ ATPase activity in tubulovesicles was diminished 1 h after
      omeprazole intake, and the activity in intracellular canaliculi was completely
      inhibited even 3 h after omeprazole administration. These results show that
      omeprazole inhibited the H(+)-K+ ATPase activity in both intracellular canaliculi
      and tubulovesicles.

PMID- 9232187
TI  - A temporal extension to the parsimonious covering theory.
AB  - In this paper, parsimonious covering theory is extended in such a way that
      temporal knowledge can be accommodated. In addition to causally associating
      possible manifestations with disorders, temporal relationships about duration and
      the time elapsed before a manifestation comes into existence can be represented
      by a graph. Precise definitions of the solution of a temporal diagnostic problem
      as well as algorithms to compute the solutions are provided. The medical
      suitability of the extended parsimonious cover theory is studied in the domain of
      food-borne disease.

PMID- 9232188
TI  - INKBLOT: a neurological diagnostic decision support system integrating causal and
      anatomical knowledge.
AB  - As an initial step in the diagnostic process, human neurologists often use
      anatomical localization to constrain the set of diagnostic hypotheses deserving
      further consideration. We describe an automated system, INKBLOT-1, which uses
      anatomical localization in much the same way as human neurologists. Given a set
      of manifestations, INKBLOT-1 generates a set of hypothetical localizations
      relative to a coordinate system of nested cubes and then uses these
      localization(s) to explain the manifestations. We trace the reasoning mechanism
      utilized by INKBLOT-1 for a particular set of symptoms and show how INKBLOT-1 is
      able to generate novel hypotheses that explain the observed manifestations. In
      doing this, INKBLOT-1 demonstrates capabilities not demonstrated by previously
      described systems.

PMID- 9232189
TI  - Avoiding premature closure in sequential diagnosis.
AB  - An important aspect of diagnostic reasoning is the ability to recognise when
      there is sufficient evidence to enable a working diagnosis to be made and thus
      avoid the unnecessary risks and costs of further testing. On the other hand, the
      reasoner must be careful to avoid the error, known as premature closure, of
      accepting a diagnosis before it is fully verified. In the absence of a more
      rigorous approach to verification, a pragmatic approach adopted in many programs
      for sequential diagnosis is to discontinue testing when the probability of the
      leading hypothesis reaches an arbitrary threshold. Experimental results are
      presented to illustrate the potential unreliability of this approach. A more
      reliable way to avoid premature closure is to discontinue testing only when the
      lower bound for the probability of the leading hypothesis reaches an acceptably
      high level. For example, a lower bound of 70% means that its probability can
      never be less than 70% regardless of any evidence that further testing may
      reveal. Another reason to discontinue testing may be that further evidence can at
      best increase the probability of the leading hypothesis by a small amount. For
      example, if the probability of the leading hypothesis is 72%, with a lower bound
      of 65% and an upper bound of 75%, further testing may be difficult to justify. As
      these examples illustrate, a termination strategy informed by upper and lower
      bounds for the probability of the leading hypothesis may help to avoid both
      premature closure and undue prolongation of the testing process. Finding upper
      and lower bounds for the probability of a diagnostic hypothesis as each new piece
      of evidence is obtained is feasible by existing techniques only when the number
      of remaining tests is small. However, new techniques are presented which can
      often produce a dramatic reduction in the computational effort required to find
      the upper and lower bounds. Based on the independence Bayesian framework, the
      theory presented extends a probabilistic model of hypothetico-deductive reasoning
      designed to enable programs for sequential diagnosis in medicine to emulate the
      reasoning processes of human diagnosticians.

PMID- 9232190
TI  - DAX1 gene expression upregulated by steroidogenic factor 1 in an adrenocortical
      carcinoma cell line.
AB  - Two nuclear hormone receptor superfamily members, DAX1 and SF1, are required for
      normal adrenal cortical development. Mutations in DAX1 are responsible for X
      linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism.
      Steroidogenic Factor 1 (SF1) regulates the expression of a number of
      steroidogenic genes and a putative SF1 response element (SF1-RE) in the DAX1
      promoter which binds SF1 specifically. Therefore, we examined deletions in the
      DAX1 promoter driving expression of beta-galactosidase, with and without
      coexpression of SF1, in the human adrenocortical carcinoma cell line NCI-H295. We
      defined the DAX initiation start site and localized the putative SF1-RE at -135
      to -143 bp. Loss of the putative SF1-RE region or specific removal of the 9-bp
      SF1 site resulted in decreased transcriptional activity by 2.3-to 2.5-fold. When
      cotransfected with 1550 bp of the DAX1 promoter, an SF1-containing expression
      vector increased the transcriptional activity of the DAX1 promoter by 4-fold. No
      significant change above baseline occurred when the cells were cotransfected with
      the 1541-bp fragment containing the entire 1550-bp promoter region minus the 9-bp
      SF1-RE. We conclude that the SF1-RE is an enhancer element within the DAX1
      promoter and speculate that SF1 may be a transcription factor that acts, at least
      in part, through DAX1 for normal adrenal cortical development.

PMID- 9232191
TI  - Identification of a splice site mutation in the cystathionine beta-synthase gene
      resulting in variable and novel splicing defects of pre-mRNA.
AB  - We used single-strand conformational polymorphism and direct nucleotide
      sequencing to identify a novel mutation in the cystathionine beta-synthase (CBS)
      gene of two siblings with homocystinuria. Both patients are heterozygous carriers
      of the G919A transition and the novel mutation which involves a G-to-A transition
      in the intron 12 splice donor site. Reverse transcription of RNA harvested from
      transformed lymphocytes followed by PCR showed a normal size product along with
      two shorter products involving the deletion of either exon 12 alone or both exons
      11 and 12. To our knowledge, the skipping of more than one exon through a single
      base substitution at a splice-donor site has not been previously reported. The
      normal size splice product was found to have either a G or an A at nucleotide
      position 919, indicating that normal size mRNA was produced by both alleles.

PMID- 9232192
TI  - Isolation and characterization of the murine homolog of the human EXT2 multiple
      exostoses gene.
AB  - Multiple exostoses is a polygenic disease of bone formation and development
      characterized by the presence of cartilage-capped osseous projections emanating
      from the end of the long bones. Two members of a recently defined multigene
      family of proteins (EXT1 and 2) were shown to be involved in this disease. To
      investigate the evolutionary relatedness of EXT genes across species we isolated
      the mouse EXT2 cDNA. As in the human counterpart, the mouse EXT2 cDNA contains an
      open reading frame of 2154 bp encoding a predicted protein of 718 amino acids.
      The nucleic acid sequence is 87% identical to the human EXT2 transcript,
      resulting in an amino acid sequence which is 95% identical to the human protein.
      The mouse EXT2 gene also shows significant sequence similarity to the mouse and
      human EXT1 gene. Northern blot analysis shows that this gene is expressed in
      early stages of embryonic development, and in situ hybridizations suggest that
      EXT2 plays a role in limb development. The identification of the mouse EXT2 gene
      will allow functional analysis through insertional inactivation and reverse
      genetics in mice in order to better understand the formation of exostoses during
      bone formation.

PMID- 9232193
TI  - Mutation (Q456H) is the most common cause of profound biotinidase deficiency in
      children ascertained by newborn screening in the United States.
AB  - Biotinidase deficiency is an autosomal recessive disorder that can result in
      neurologic and cutaneous symptoms if not treated with biotin supplementation. We
      have identified the most common cause of profound biotinidase deficiency in
      children ascertained by newborn screening in the United States. 1368A-->C results
      in a substitution of histidine for glutamine 456 (Q456H) in exon D of the
      biotinidase gene. This mutation was found in at least one allele in 14 unrelated
      children from 27 different families or 15 of 54 alleles studied (28%). This
      mutation was not identified in 41 normal adults using SSCA, nor was it found in
      296 normal newborns using allele-specific oligonucleotide analysis, suggesting
      that this change is not a polymorphism. In addition, biochemical data from a
      child homozygous for Q456H suggest that the aberrant enzyme has very low biotinyl
      hydrolase activity, lacks biotinyl-transferase activity, and is not recognized by
      antibody prepared to purified, normal human biotinidase. The ethnic backgrounds
      of the parents contributing the Q456H allele are varied but are generally
      northern European.

PMID- 9232194
TI  - Risk of neural tube defect-affected pregnancy is associated with a block in
      maternal one-carbon metabolism at the level of N-5
      methyltetrahydrofolate:homocysteine methyltransferase.
AB  - The disposition of whole blood mono-to hexaglutamyl methylfolate and plasma
      homocysteine (HCY) was used to evaluate potential lesion sites in one-carbon
      metabolism which could be responsible for neural tube defect(NTD)-affected
      pregnancies. An isocratic high-performance liquid chromatographic system (HPLC)
      with photodiode array detection was used to quantify and speciate whole-blood
      methylfolate into mono-, di-, tri-, tetra-, penta-, and hexaglutamate forms. This
      technique was also used with off-line radioassay to identify nonmethyl whole
      blood folates. Isocratic HPLC with fluorescence detection was used to quantify
      SBDF derivatized homocysteine in plasma. The study investigated blood from 11
      women who had experienced a previous NTD-affected pregnancy and 11 controls of
      similar age and social class. No subjects were pregnant. HCY levels were
      significantly higher in NTD subjects (P = 0.0486, 95% CI-2.799,0.001 using the
      Mann-Whitney test), as was the ratio of known intracellular (tri-to hexaglutamyl)
      methylfolate compared to extracellular (mono- and diglutamyl) methylfolate (P =
      0.0062 95% CI-0.543, 3.862 using the Mann-Whitney test). Vitamin B12, red cell
      folate, circulating total methylfolate, and circulating mono-to hexaglutamyl
      methylfolates showed no difference between population groups. The disposition
      between individual and cumulative glutamate chain lengths of methylfolate showed
      significant trends which differed between population groups: (i) total blood
      methylfolate (Glu1-6) appears to be utilized by N-5
      methyltetrahydrofolate:homocysteine methyltransferase (MS) in control blood but
      not NTD blood, where it appears to accumulate following a 45-min incubation; (ii)
      whole-blood hexaglutamyl methylfolate (5CH3-H4PteGlus) becomes a larger
      proportion of the total blood methylfolate in NTD than in control populations;
      and (iii) the intermediate glutamate chains of methylfolate (Glu1-5) remain
      relatively constant as 5CH3-H4PteGlu6 accumulates in NTD but appear to increase
      linearly with 5CH3-H4PteGlu6 in controls. The significant elevation of HCY in the
      NTD population is associated with the increasing proportion of 5CH3-H4PteGlu6
      relative to the total methylfolate, since, when corrected for HCY level, the
      proportion of 5CH3-H4PteGlus to total methylfolate is similar in NTD and control
      populations. These trends are consistent with a defect at the level of vitamin
      B12 dependent MS which "traps" folate at the 5CH3-H4PteGlus level.

PMID- 9232195
TI  - An enzyme immunoassay for neuron-specific enolase in cerebrospinal fluid.
AB  - A direct (as opposed to competitive) enzyme immunoassay (EIA) was developed to
      detect neuron-specific enolase (NSE) in cerebrospinal fluid (CSF). Most common
      methods of evaluating NSE levels have utilized radioimmunoassay. These are highly
      sensitive, but cannot be employed in laboratories not equipped or licensed for
      the use of radioisotopes. The EIA developed here shows sensitivity within the
      physiological range of values for CSF-NSE (> I ng/ml) and can be used in
      laboratories with appropriate densitometric scanning capabilities. The assay was
      applied to CSF samples obtained from patients with a variety of diagnoses at the
      time of surgical intervention for their respective disorders. While there were no
      diagnostically significant differences between the level of NSE in CSF from
      patients with different neurological disorders utilized in the development of
      this procedure, we were able to differentiate between marginally different levels
      of NSE. We conclude that we have developed a safe, fast, reliable, and sensitive
      assay for NSE in the CSF that can be used to study NSE levels in a variety of
      neurological cases.

PMID- 9232196
TI  - Comparison of the hydrolysis of the three types of natriuretic peptides by human
      kidney neutral endopeptidase 24.11.
AB  - The degradation of 3 human natriuretic peptides by human kidney neutral
      endopeptidase 24.11 has been investigated. The studies revealed that hANP-28 and
      hCNP-22 are the preferred substrates, whereas hBNP-32 is not. The enzyme has been
      known to inactivate hANP-28 from cleavage at the Cys-Phe bond at the beginning of
      its ring structure. Analysis of the cleavage sites of each peptide indicated that
      the initial cleavage site of hCNP-22 is analogous to that of hANP-28. The Cys-Phe
      bond of hBNP-32 was insensitive to this enzymatic cleavage. We speculate that the
      stability of hBNP-32 may result from the insusceptibility of its Cys-Phe bond at
      the beginning of the ring structure.

PMID- 9232197
TI  - Histidine modification of human serum butyrylcholinesterase.
AB  - The effects of histidine-modifying reagents on human serum butyrylcholinesterase
      (BChE) were investigated. The commercially available enzyme was further purified
      by chromatography on a Sepharose CI-6B column prior to use. In the modification
      studies, we found that the histidine-specific reagents tosylphenylalanine
      chloromethyl ketone (TPCK) and tosyllysine chloromethyl ketone (TLCE) did not
      modify the enzyme; however, they inhibited the enzyme reversibly. The kinetic
      parameters of enzyme inhibition calculated were alpha = 10.8, beta = 0.26, and Ki
      = 0.016 mM for TPCK. TLCK inhibition gave similar kinetic behavior, with alpha =
      41.6, beta = 0.065, and Ki = 0.039 mM. Tosyllysine, an analog of TLCK, did not
      inhibit the enzyme. Removal of TPCK and TLCK by dialysis resulted in significant
      reactivation of the enzyme. From kinetic studies, it was found that the
      inhibitions were hyperbolic mixed-type inhibitions. We concluded that the
      reagents competed with substrate for hydrophobic binding sites and inhibited the
      enzyme reversibly. On the other hand, in the modification studies with diethyl
      pyrocarbonate (DPC), it was observed that inactivation of the enzyme was
      irreversible and time-dependent. In the protection studies, the activity of the
      enzyme was partially protected from inactivation by DPC even at a 50 mM
      concentration of butyrylthiocholine. The results indicate that DPC modifies some
      essential histidine side chains in BChE, including the functional histidyl
      residue found at the active site.

PMID- 9232198
TI  - Diabetes-induced apoptosis in rat kidney.
AB  - Oxidative stress has been suggested to play a crucial role in the pathogenesis of
      diabetic complications including nephropathy. However, the exact mechanism of
      diabetic nephropathy is still not clearly understood. Since oxidative stress in
      known to be a major component in the induction of apoptosis, we investigated the
      occurrence of apoptosis in diabetic rat kidney. The status of oxidative stress
      was determined as thiobarbituric acid reactive substances (TBARS). The TBARS in
      the control and diabetic rat kidney were 2.00 +/- 0.963 and 3.83 +/- 0.715
      mumol/mg protein, respectively (P < 0.05). Apoptosis was determined by evaluating
      the DNA fragmentation using an enzyme-linked immunoassay and in situ end
      labeling. DNA fragmentation increased approximately fourfold in diabetic rat
      kidney compared to the normal kidney (P < 0.05). Apoptag in situ labeling
      displayed negligible apoptosis in nondiabetic kidney while significant areas of
      apoptosis were observed in diabetic kidney. Our results suggest that increased
      oxidative stress in diabetic kidney could induce apoptosis, which may contribute
      to the development of diabetic nephropathy.

PMID- 9232199
TI  - Leukotriene synthesis by isolated perinatal ovine intrapulmonary vessels
      correlates with age-related changes in 5-lipoxygenase protein.
AB  - Leukotrienes (LT) are potent vasoconstrictors in the pulmonary circulation. We
      have investigated the synthesis of LTC4 by intrapulmonary arteries and veins of
      perinatal lambs. Paired vessels of near-term fetal 146 +/- 2- and 2- to 7-day-old
      newborn lambs (each n = 7), were incubated for 10 min at 37 degrees C in
      baseline, with 1 mumol/L A32187 or 0.1 mmol/L arachidonic acid. Produced
      leukotriene C4 was assayed from media by ELISA. Baseline production of
      leukotriene (ng/mg tissue, means +/- SEM) by vessels for arteries was 0.006 +/-
      0.001 and 0.059 +/- 0.009 for fetus and newborn, respectively. In veins, the
      values were 0.013 +/- 0.003 and 0.073 +/- 0.007 for fetus and newborn,
      respectively. On stimulation with the calcium ionophore A23187, production by
      arteries increased 25-fold in the fetus, but 4-fold in the newborn. The
      corresponding values for stimulated veins were 37-fold and 9-fold in fetus and
      newborn, respectively. Generally, production by veins was greater than production
      by the matching arteries. In all instances, the fetal vessels produced less
      leukotrienes than the newborn vessels. Western analysis of stimulated and
      unstimulated vessel membrane protein showed greater expression of 5-lipoxygenase
      in veins than in arteries (P < 0.05). Our data show that veins produce more LTC4
      due to greater expression of 5-lipoxygenase in the vessels and thus suggest that
      veins of perinatal lamb lungs may be more susceptible to LT-induced
      vasoreactivity in the perinatal pulmonary circulation. We speculate that a higher
      production of LTC4 by fetal veins may be necessary to maintain a high venous tone
      in fetal lungs.

PMID- 9232200
TI  - Effects of dehydroepiandrosterone in rats injected with streptozotocin during the
      neonatal period.
AB  - Control rats and diabetic animals injected with streptozotocin during the
      neonatal period were either maintained on a standard diet or given access to food
      supplemented with dehydroepiandrosterone (DHEA, 0.2%) for 11 days before
      sacrifice. In both control and diabetic rats, DHEA feeding augmented the activity
      of the mitochondrial FAD-linked glycerophosphate dehydrogenase and cytosolic NADP
      linked malate dehydrogenase in liver, but not so in either the parotid gland or
      pancreatic islets. DHEA lowered, in both control and diabetic rats, the ratio
      between D-glucose oxidation and utilization and the rate of insulin release in
      pancreatic islets exposed to a high concentration of D-glucose, as well as the
      insulin concentration and insulin/glucose ratio in plasma. These findings support
      the view that, in diabetes, DHEA, by increasing sensitivity to insulin, may allow
      islet B-cells to avoid the otherwise unfavorable consequences of chronic
      hyperactivity.

PMID- 9232201
TI  - Inhibition of transforming growth factor beta 1 induction by dietary vitamin E in
      unilateral ureteral obstruction in rats.
AB  - Free radical species associated with bilateral ureteral obstruction (BUO) are
      considered important in the pathogenesis of the glomerular and tubulointerstitial
      injury in BUO rats. We seek to test the hypothesis that the use of an easily
      administered antioxidant, vitamin E, at sufficient plasma concentrations, can
      decrease this release of free oxygen radicals in kidney tissue and ameliorate the
      increase of the fibrogenic cytokine, transforming growth factor beta-1 (TGF beta
      1). We used the unilateral ureteral obstruction (UUO) rat model, because the
      presence of the uninjured contralateral kidney provides a nonuremic internal
      milieu, in contrast to the uremic, acidotic, and hypercholesterolemic BUO model.
      Compared to sham controls, the UUO animals showed a dramatic increase in renal
      cortical TGF beta-1 mRNA, as quantitated by Northern blot analysis with
      cyclophilin internal standards. This increase in TGF beta-1 mRNA was reversed in
      UUO rats treated with vitamin E. The plasma malondialdehyde (MDA) concentration,
      an index of lipid peroxidation and an indirect index of free radical release, was
      significantly elevated in UUO animals compared to sham animals. The vitamin E
      treated UUO animals showed a significant decrease in both plasma and renal
      cortical tissue MDA content. Taken together, these findings provide evidence of
      the important biological role of reactive free radical species in the
      tubulointerstitial injury of UUO and the novel role of vitamin E in modulating
      the mRNA of the fibrogenic TGF beta-1 in obstructive uropathy.

PMID- 9232202
TI  - The increased skeletal muscle protein turnover of the streptozotocin diabetic rat
      is associated with high concentrations of branched-chain amino acids.
AB  - Experimental streptozotocin-induced diabetes resulted in important changes in
      body weight which were associated with abnormalities in water and food intake. In
      addition, diabetic rats showed a clear muscle atrophy involving a decrease in
      both skeletal muscle size and protein content. This was accompanied by a marked
      loss of total carcass nitrogen. These changes were related to important
      alterations in protein turnover in skeletal muscle. Thus, the diabetic animals
      showed changes in the fractional protein rates of both synthesis (decreased by
      37%) and degradation (increased by 140%). The increased protein degradation
      observed in the muscle of the diabetic animals was associated with important
      changes in the concentration of both circulating and muscle amino acids.
      Interestingly, the diabetic animals did not show important changes in either
      liver or kidney protein turnover rates, in spite of having a clear increase (over
      50%) in kidney mass. In addition, and although the total amino acid concentration
      was not affected by the diabetic state, the chemically induced diabetic animals
      showed important elevations of branched-chain amino acids (leucine, isoleucine,
      and valine) in both blood and skeletal muscle. Similarly, important decreases in
      the blood concentrations of glutamate+glutamine, alanine, glycine, proline,
      serine, and threonine were also observed. These observations reinforce the idea
      of the association between muscle protein wasting, increased protein turnover,
      and alterations in branched-chain amino acids previously proposed by our group.

PMID- 9232203
TI  - Human seminal plasma soluble 5'-nucleotidase: regulatory aspects of the
      dephosphorylation of nucleoside 5'-monophosphates.
AB  - Human seminal plasma contains two enzyme activities both capable of
      dephosphorylating all nucleoside 5-monophosphates with different efficiency and
      specificity. Broad-spectrum soluble 5'-nucleotidase is the object of this paper
      which deals with the definition of the response of this enzyme to effectors, some
      physiological and others not naturally occurring. The enzyme did not show any
      product regulation as all the nucleosides tested caused a moderate effect on the
      hydrolysis of the substrates. Theophylline and other xanthine derivatives had no
      effect on enzyme activity, whereas glycerate 2,3-bisphosphate, like other soluble
      5'-nucleotidases, caused a stimulation of the enzyme, especially toward CMP and
      UMP. 5-Deoxy-5-isobutylthiadenosine resulted in no inhibition of the hydrolysis
      of AMP and IMP. The enzyme was affected neither by monovanadate nor by
      decavanadate, whereas it was strongly inhibited by Ap5 A. Variations in adenylate
      energy charge did not cause any alteration of the enzyme activity toward AMP and
      only a slight decrease of the hydrolysis of IMP. These regulatory properties,
      distinct from those of other soluble 5'-nucleotidases, show that this form, newly
      isolated from human seminal plasma, is subject to an almost unique, tissue
      specific regulation.

PMID- 9232204
TI  - Expression study of survival motor neuron gene in human fetal tissues.
AB  - In order to investigate the spinal muscular atrophy (SMA) disease processes, the
      expression of the survival motor neuron gene (SMN) has been analyzed in human
      fetal tissues using RT-PCR and in situ hybridization. These studies allowed the
      detection of SMN RNA in all the examined tissues, with no significant variation
      between different developmental stages. In particular, SMN mRNA was detected in
      spinal cord (dorsal and ventral portions), skeletal muscle, lung, heart, kidney,
      liver, and spleen. Moreover, RT-PCR studies demonstrated that the expression
      pattern of SMN isoforms was similar to that observed in adult tissues. The
      present data confirm a housekeeping role for the SMN protein and may have
      implications on the search for early therapeutic strategies.

PMID- 9232206
TI  - Active form of Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A
      reductase.
AB  - Based on multiple gel permeation chromatographic experiments, we report a Stokes
      radius of 59.7 A for Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A
      reductase (HMG-CoA reductase; EC 1.1.1.88) and its His381Asn, His381Gln, and
      His381Lys mutant enzymes. Comparison of this Stokes radius with the radius
      calculated from the crystal structure indicated that the active form of P.
      mevalonii HMG-CoA reductase was a hexamer and not a dimer as previously thought.
      The Stokes radius, an S26,w of 11.0, and an estimated V of 0.723 were used in the
      Svedberg equation to calculate an anhydrous molecular mass of 270,084 Da for P.
      mevalonii HMG-CoA reductase (monomer mass 45,538 Da), consistent with the enzyme
      being a hexamer in solution. The Stokes radii of all standard proteins examined
      correlated with the inverse error function complement of their partition
      coefficient, Kd. Kd did not correlate with logarithm of the standard protein's
      molecular weight. Eight nonstandard proteins had Stokes radii that matched their
      crystallographic radii of longest axis. This indicated that the frozen
      conformation of a protein in its crystal form can dictate restraints on its shape
      in solution.

PMID- 9232205
TI  - The mechanisms of compound 48/80-induced superoxide generation mediated by A
      kinase in rat peritoneal mast cells.
AB  - This investigation was undertaken to clarify the mechanisms of superoxide anion
      (O2-) generation in rat peritoneal mast cells. Compound 48/80, a typical
      histamine liberator mediated by calcium influx, elicited O2- generation from the
      mast cells in a dose-dependent fashion. It was demonstrated by
      immunohistochemical study and Western blot analysis that the mast cells contained
      the 47-kDa phagocyte oxidase (p47phox) protein, which was one cytosolic component
      of the NADPH oxidase system. Arachidonic acid stimulated O2- generation in the
      mast cells, but other unsaturated fatty acids had no effect. On the other hand,
      48/80-induced O2- generation was inhibited by phospholipase A2 inhibitors, such
      as arachidonyl trifluoromethyl ketone and manoalide. Forskolin, isoprenaline, and
      dibutyryl cyclic AMP inhibited the O2- generation, and KT-5720, a cyclic AMP
      dependent protein kinase (A-kinase) inhibitor, markedly enhanced the O2-
      generation. These findings suggest that O2- is generated by a NADPH oxidase-like
      enzyme system in mast cells and that this enzyme system is activated by
      arachidonic acid released by cytosolic phospholipase A2. Thus, it is regulated by
      the cyclic AMP-A kinase system.

PMID- 9232207
TI  - Antipsychotic regulation of hippocampal dopamine receptor messenger RNA
      expression.
AB  - Medial temporal lobe structures including the hippocampus and entorhinal cortex
      have been implicated in the pathophysiology of schizophrenia. Markers of
      dopaminergic neurotransmission indicate that these regions receive dopaminergic
      innervation. Accordingly, dysfunction of dopaminergic neurotransmission within
      the hippocampus and associated cortical areas may be associated with
      schizophrenia. Little is known, however, about the expression and regulation of
      dopamine receptors in these regions. We determined the effects of 14 days of
      clozapine or haloperidol treatment on dopamine receptor messenger RNA (mRNA)
      expression in medial temporal regions of the rat brain by in situ hybridization.
      These two drugs had different effects in the hippocampus and entorhinal cortex,
      particularly a dissociation of their effects on D2 and D3 receptor mRNA
      expression. There was a parallel down-regulation of D4 mRNA by both drugs. D1 and
      D5 transcripts were not regulated by either treatment. These results suggest a
      differential pattern of regulation of D2-like receptor expression by clozapine
      and haloperidol in some medial temporal lobe structures. These drugs also appear
      to cause changes in the expression of these transcripts that differ from what has
      been reported in the striatum, adding to a growing literature suggesting that
      hippocampal and striatal dopamine receptors are differentially regulated.

PMID- 9232208
TI  - Low cerebrospinal fluid corticotropin-releasing hormone concentrations in
      eucortisolemic depression.
AB  - Hypersecretion of corticotropin-releasing hormone (CRH) and resulting
      hypercortisolism have been implicated in the pathogenesis of major depression. To
      test this CRH hypersecretion hypothesis, cerebrospinal fluid (CSF) was
      continuously withdrawn from 11:00 AM to 5:00 PM via an indwelling subarachnoid
      catheter (placed at 8:00 AM), and immunoreactive CRH concentrations were
      determined at 10-min intervals in 10 depressed patients, the majority of whom
      exhibited at least one "atypical" symptom, and in 15 normal volunteers. CSF CRH
      was low, plasma adrenocorticotropin (ACTH) tended to be low, and plasma cortisol
      was normal in the depressed patients. Also, tobacco smokers had lower CSF CRH
      than nonsmokers. CRH increased acutely in response to lumbar puncture, had a
      brief half-life, showed rapid variability in concentration over time, and
      displayed a diurnal concentration rhythm that was preserved in fasting
      individuals and in most depressed patients. CSF CRH did not correlate with plasma
      ACTH or cortisol; this and its rapidly fluctuating levels suggest a primarily
      extrahypothalamic origin of lumbar CSF CRH.

PMID- 9232209
TI  - Plasma prolactin response to d-fenfluramine in obsessive-compulsive patients
      before and after fluvoxamine treatment.
AB  - The prolactin (PRL) responses to oral d-fenfluramine (30 mg) and placebo were
      assessed in 13 patients with obsessive-compulsive disorder (OCD) and in matched
      healthy subjects. After the neuroendocrine test, all patients were treated with
      fluvoxamine maleate (150-300 mg/day). At the end of the 10th week of treatment,
      10 patients underwent again the neuroendocrine assessment. In drug-free patients,
      the PRL response to d-fenfluramine was significantly lower than in the comparison
      group. After 10-week fluvoxamine treatment, the PRL response to the serotonergic
      agent normalized. These findings suggest that, at least at the neuroendocrine
      level, central serotonergic responsivity is reduced in drug-free OCD patients,
      and that long-term fluvoxamine administration is associated with its
      normalization.

PMID- 9232210
TI  - Effect of alpha-methyl-para-tyrosine on response to cocaine challenge.
AB  - This study evaluated the effect of an acute reduction in catecholamine synthesis
      produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor,
      on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g
      p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to
      intranasal administration of 2 mg/kg cocaine. AMPT, but not placebo, reduced
      plasma levels of the dopamine metabolite homovanillic acid and the norepinephrine
      metabolite 3-methoxy-4-hydroxyphenylglycol. AMPT also elevated prolactin levels,
      indicating inhibition of the tuberoinfundibular dopamine system. AMPT
      pretreatment produced a trend toward diminished cocaine "high" AMPT also tended
      to lower heart rate and blood pressure responses to cocaine, but had no effect on
      serum cocaine levels. Although we cannot rule out the therapeutic potential of
      the depletion strategy, our results with AMPT alone, at this dose, do not
      strongly support it.

PMID- 9232211
TI  - Sleep-onset rapid eye movement after electroconvulsive therapy is more frequent
      in patients who respond less well to electroconvulsive therapy.
AB  - The response to electroconvulsive therapy (ECT) was monitored with sleep
      polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with
      major depressive disorder (MDD). Patients included in this study met research
      diagnostic criteria for MDD and had been free of psychotropic medication for at
      least 10 days before SPS were performed. We compared ECT responders and
      nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters,
      regardless of the clinical response, changed significantly with ECT. The presence
      of delusions was significantly associated with SOREM post-ECT. The presence of
      sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS
      performed during a course of ECT may help identify patients at risk of responding
      less well to this modality of treatment.

PMID- 9232212
TI  - No early effects of electroconvulsive therapy on tryptophan metabolism and
      disposition in endogenous depression.
AB  - The possibility that a single electroconvulsive therapy (ECT) could increase
      tryptophan (Trp) availability to the brain for 5-hydroxytryptamine (5-HT,
      serotonin) synthesis was examined in 10 depressed patients before and during the
      1st hour following an ECT and in 4 control (minor ear, nose, and throat surgical)
      subjects receiving similar premedication. Trp availability to the brain,
      expressed as the serum Trp: competing amino acid ratio, and related aspects of
      Trp disposition were not significantly altered by ECT any differently than from
      preoperative stress and premedication. We suggest that Trp availability to the
      brain and, hence, cerebral 5-HT synthesis are not altered in depressed patients
      early after a single ECT.

PMID- 9232213
TI  - The effect of cholecystokinin tetrapeptide on respiratory resistance in healthy
      volunteers.
AB  - The effects of cholecystokinin tetrapeptide (CCK-4) on respiratory resistance
      were studied in 14 healthy volunteers by the registration of slow vital capacity
      and flow volume loop during forced respiration test. The administration of CCK-4
      (50 micrograms) was performed in a double-blind and placebo-controlled design.
      Injections of CCK-4 induced prominent and time-limited paniclike symptoms in all
      healthy volunteers. Four volunteers (29%) experienced a panic attack. Subjective
      dyspnea was experienced by the majority of subjects at the peak of CCK-4 effect
      and seemed related to a diminution in vital capacity parameters; however, the
      forced respiration test did not reveal bronchoconstriction after CCK-4 challenge.
      Administration of CCK-4 also induced a short-lasting increase in heart rate and
      skin blood flow. This study suggests that dyspnea induced by CCK-4 is not related
      to changes in respiratory resistance.

PMID- 9232214
TI  - Neuropathology of the cerebellum in schizophrenia--an update: 1996 and future
      directions.

PMID- 9232215
TI  - Apolipoprotein E-epsilon 4 frequency in patients with schizophrenia.

PMID- 9232217
TI  - Stimulant sensitization in humans.

PMID- 9232216
TI  - The calpain-calpastatin system in obsessive-compulsive disorder.

PMID- 9232218
TI  - Rapid quantification of DNA samples extracted from buccal scrapes prior to DNA
      profiling.

PMID- 9232219
TI  - Construction of a library for sequencing long regions of malarial genomic DNA.

PMID- 9232220
TI  - Reversal of RT-PCR inhibition observed in heparinized clinical specimens.

PMID- 9232221
TI  - mRNA differential display in agarose gels.

PMID- 9232222
TI  - Quantitative RT-PCR using a PCR-generated competitive internal standard.

PMID- 9232223
TI  - Combining multiplex and touchdown PCR to screen murine microsatellite
      polymorphisms.

PMID- 9232224
TI  - Minisatellite variant repeat coding using a semiautomatic system.

PMID- 9232225
TI  - Efficient non-PCR-mediated overlap extension of PCR fragments by exonuclease "end
      polishing".

PMID- 9232226
TI  - Combination of direct DNA sequencing with degenerate primer-mediated PCR and 5'
      /3'-RACE to screen novel cDNA sequences.

PMID- 9232227
TI  - Sequence-dependent separation of DNA fragments by capillary electrophoresis in
      the presence of SYBR Green I.

PMID- 9232228
TI  - Determination of molecular weights of nucleic acid-binding proteins by UV photo
      crosslinking and SDS-PAGE.

PMID- 9232229
TI  - EGFP-containing vector system that facilitates stable and transient expression
      assays.

PMID- 9232230
TI  - Reliable method of isolating transfected clones from the LNCaP human prostatic
      cell line.

PMID- 9232231
TI  - Rapid microplate assay for substrates and inhibitors of proteinase mixtures.

PMID- 9232232
TI  - Isolation of site-specific insert probes from chimeric YACs.

PMID- 9232233
TI  - Method of data analysis that elucidates contributions to the T-cell receptor
      repertoire.

PMID- 9232234
TI  - Intracellular expression and purification of the c-kit receptor kinase domain in
      Pichia pastoris.

PMID- 9232235
TI  - Generation of a moveable poly(A)+ cassette.

PMID- 9232236
TI  - Detection and analysis of living, growth-inhibited mammalian cells following
      transfection.

PMID- 9232237
TI  - Epitope tag-antibody combination useful for the detection of protein expression
      in prokaryotic and eukaryotic cells.

PMID- 9232238
TI  - Direct primer walking on P1 plasmid DNA.

PMID- 9232239
TI  - Fabrication of ion-selective microelectrodes by a centrifugation/suction method.

PMID- 9232240
TI  - Magnetic bead technology aids sequence determinations for the 3' and 5' ends of
      viral RNAs.

PMID- 9232241
TI  - Mini-exon epitope tagging for analysis of the protein coding potential of genomic
      sequence.
AB  - A novel approach to gene discovery and analysis is described. A small exon
      flanked by consensus 3' and 5' splice sites was synthesized. The exon contains
      open reading frames encoding 43 amino acid peptides. There are no stop codons in
      any of the three reading frames, and each reading frame contains an epitope
      recognized by the same monoclonal antibody. The exon can be inserted into the
      introns of genes, and the resulting small peptide will be incorporated into the
      protein encoded by the host gene, regardless of the class of intron. The protein
      can then be recognized by the antibody, permitting functional studies.

PMID- 9232242
TI  - Direct hybridization of large-insert genomic clones on high-density gridded cDNA
      filter arrays.
AB  - A major challenge to positional cloning approaches is the identification of
      coding sequences within a region of interest. Hybridization of genomic fragments
      that represent a cloned contig of a defined genomic region in appropriate cDNA
      libraries theoretically represents a direct solution to this problem. However,
      this is technically difficult and in general, success with this approach has been
      limited to the use of small fragments, such as those cloned in cosmids and
      phages. Since most physical maps are composed of genomic DNA cloned in vectors
      with significantly greater insert size capacity, there is a need to develop
      efficient methods to use these clones directly as hybridization probes. Here we
      describe a highly sensitive protocol for hybridization of P1-derived artificial
      chromosomes (PACs; average insert size, 120 kb) on a composite, normalized cDNA
      library comprised of 200000 clones spotted at high density on nylon filters.
      Because limited sequence information on more than 150000 of these clones is now
      available in the public domain, positive hybridization results can be rapidly
      converted to cDNA sequence information without recourse to any clone manipulation
      in the initial phases of a project. Using these protocols, we have been able to
      reproducibly detect coding exons that constitute as little as 0.2% of the total
      PAC insert.

PMID- 9232243
TI  - Cycle sequencing of filamentous phage DNA using a biotinylated primer and delta
      Taq DNA polymerase.

PMID- 9232244
TI  - Presence of RNase A causes aberrant DNA band shifts.
AB  - RNase A, which is routinely added during DNA purification to reduce contaminating
      RNA, causes shifting of DNA bands in agarose gels. DNA band sizes on agarose gels
      increase as much as 10%-20% when RNase A is present. The low concentrations of
      RNase A typically used to purify DNA cause shifting of select DNA bands, in
      contrast to higher concentrations of RNase A where all band are shifted and
      smeared. The binding of RNase A to the DNA is specific and the degree of the
      shift varies; not all DNA bands are retarded, and the deviation is more
      pronounced in certain buffers. Other proteins, such as bovine serum albumin or
      proteinase K, do not induce DNA band shift, suggesting the interaction is
      specific. The binding of RNase A to DNA is reversible. The formation of RNase:DNA
      complexes may affect experiments involving DNA:protein interactions such as gel
      shift, footprinting and filter binding assays. Researchers performing DNA
      characterization from miniprep protocols should be aware that RNase may cause the
      apparent sizes of DNA fragments to be altered and obscure the presence of very
      small cloned fragments.

PMID- 9232245
TI  - Amplification of 4-9-kb human genomic DNA flanking a known site using a panhandle
      PCR variant.
AB  - We present a method for the in vitro amplification of > 6.0 kb of DNA flanking a
      known site. This is accomplished by ligating an oligonucleotide to create an
      inverted repeat of a portion of the known sequence, followed by single-primer
      polymerase chain reaction (PCR) amplifications. This method generates a panhandle
      template following primer extension on the strand of interest. It does not
      involve template-directed extension from the ligated oligonucleotide, and it is
      carried out without DNA extractions. We have used this method to amplify 4.5-9.4
      kb of DNA flanking the original primer annealing sites directly from human
      genomic DNA.

PMID- 9232246
TI  - Protein/amphipathic polyamine complexes enable highly efficient transfection with
      minimal toxicity.
AB  - Ternary complexes of plasmid DNA, histone H1 protein and amphipathic polyamines
      (PAPA) were able to mediate the efficient transfection of 3T3. HeLa and COS cells
      in culture. Using both the beta-galactosidase and luciferase reporter gene
      systems, the transfection efficiency of PAPA complexes was comparable to that of
      DOSPA/PE cationic liposomes, considered to be a highly-efficient transfection
      reagent. Using three different assays of cellular toxicity (propidium iodide,
      BCECF-AM and Trypan Blue), the PAPA complexes caused minimal cellular toxicity.
      These results indicate that PAPA complexes are useful transfection reagents for
      the study of gene expression and function in cultured cells.

PMID- 9232247
TI  - Fluorescence imaging in human identity testing.
AB  - We have investigated the use of fluorescence detection and the FluorImager S1
      System (Molecular Dynamics) for analyzing a comprehensive set of human DNA typing
      tests. We used an alkaline phosphatase-conjugated YNH24 oligonucleotide probe to
      the repeat-containing D2S44 locus to detect both alleles in 50 ng of human
      genomic DNA (0.025 amol) by Southern hybridization using a chemifluorescent
      substrate. We used a similar approach to quantify human DNA using an enzyme
      conjugated oligonucleotide probe to the D17Z1 locus. Both fluorescent nucleic
      acid gel staining and direct fluorescent labeling methods were tested to detect
      PCR-based D1S80 and short tandem repeat (STR) multiplex allele profiles. The
      fluorescent staining method sensitively detected these allelic profiles in both
      denaturing and non-denaturing acrylamide gels using a simple, 10-min procedure.
      Fluorescent primers eliminate the doublet band patterns often seen with staining
      methods, which label both strands of the amplified products. This complicates
      interpretation of STR typing tests. Only one primer for each locus is labeled, so
      only one strand of the DNA product is detected. Fluorescein end-labeled primers
      were used in multiplex PCR to amplify, detect and type STRs.

PMID- 9232248
TI  - Peripheral stem cell mobilization and engraftment in patients over age 60.
AB  - Data from 225 multiple myeloma (MM) patients, undergoing peripheral stem cell
      (PBSC) mobilization with high-dose cyclophosphamide and hematopoietic growth
      factors, were analyzed for median CD34+ cell count and median time to post
      transplant neutrophil (ANC > 500/microliters) and platelet (> 50,000/microliters)
      recovery according to age groups (20-49, 50-59 and > or = 60 years) and duration
      of prior therapy (< or = 12, 13-24, or > 24 months). Fifty-seven of the 225
      patients were > or = 60 years. No difference in either the median number of CD34+
      cells collected or time to engraftment occurred between age groups, when adjusted
      for duration of prior therapy. These data support the concept that
      autotransplants can be performed safely in patients > or = 60 years and that
      these patients should not be excluded from the most effective treatment
      modalities.

PMID- 9232249
TI  - Allogeneic bone marrow transplantation for children with acute leukemia: long
      term follow-up of patients prepared with high-dose cytosine arabinoside and
      fractionated total body irradiation.
AB  - High-dose therapy and allogeneic matched sibling bone marrow transplantation
      (BMT) is considered to be the treatment of choice for children with relapsed
      acute lymphoblastic leukemia (ALL), or for children with acute myeloid leukemia
      (AML) in first remission. However, the rate of bone marrow relapse after
      transplant for either of these diseases remains high. In this study, we assessed
      the efficacy and toxicity of high-dose cytosine arabinoside and total body
      irradiation (TBI) followed by allogeneic BMT, for children with acute leukemia or
      myelodysplastic syndrome (MDS). Sixty-five pediatric patients underwent
      allogeneic related (n = 57) or unrelated (n = 8) BMT. Twenty-seven were
      transplanted for ALL in second remission (CR2), and 16 for AML in first remission
      (CR1). The other 22 were high risk patients: six were transplanted for ALL in
      third remission (CR3), two for AML in CR2, two for myelodysplastic syndrome (MDS)
      and 12 for acute leukemia in relapse. Patients were prepared with cytosine
      arabinoside 3000 mg/m2 per dose twice daily for 6 days followed by 12000 cGy TBI
      as 200 cGy fractions twice daily for 3 days. Minimum follow-up is 21 months. Five
      year event-free survival (EFS) and the actuarial relapse rate is 59 and 14% for
      patients with ALL in second remission, and 38 and 14+% for patients with AML in
      first remission. Twelve patients have relapsed (three are alive in remission
      after testicular or marrow relapse) and 28 have died of other causes. Acute GVHD
      with or without infection was the cause of death in 11 patients. Ten of the 11
      patients who died of acute GVHD were considered at 'high risk' for GVHD
      (inadequate GVHD prophylaxis, or mismatched family donor or a matched unrelated
      donor). Toxicities in the immediate post-BMT period included diarrhea,
      oropharyngeal mucositis and conjunctivitis. Significant late toxicities included
      short stature, avascular necrosis of bone, and poor school performance (most
      often in patients who had received prior cranial irradiation). Our conclusions
      are that high-dose Ara-C and TBI followed by allogeneic bone marrow
      transplantation is effective therapy for children in second complete remission of
      their acute leukemia. However, significant late toxicities occur, and it is clear
      that more effective, less toxic therapies are necessary for these patients.

PMID- 9232250
TI  - European results of matched unrelated donor bone marrow transplantation for
      chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia
      Working Party of the European Group for Blood and Marrow Transplantation.
AB  - We have retrospectively analyzed the impact of prognostic factors on the outcome
      of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose,
      we have studied a cohort of 366 patients transplanted in Europe between January
      1985 and December 1994. The median age of the 211 males and 155 females was 34
      years; 238 patients were transplanted in first chronic phase and 116 in advanced
      phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis
      consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell
      depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have
      been used to improve donor selection. We obtained complete data on 300
      donor/recipient (D/R) pairs. Among them, we have identified three groups of
      patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten
      patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one
      patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59
      from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The
      overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31
      +/- 3%. In univariate analysis, five variables had a favorable effect on LFS:
      transplant in first chronic phase (P = 0.0001), time interval from diagnosis to
      BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P +
      0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P =
      0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8%
      in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed
      that HLA-DRB1 matching was the most significant factor influencing survival (P =
      0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined
      a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA
      DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM
      and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%,
      respectively. This suggests that the long-term outcome of patients with favorable
      prognostic features can approach that of patients transplanted from geno
      identical siblings. In contrast, the TRM for patients transplanted for advanced
      disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly
      indicates that UD BMT is not justifiable for these individuals.

PMID- 9232251
TI  - Prognostic factors for survival after high-dose therapy and autologous stem cell
      transplantation for patients with relapsing Hodgkin's disease: analysis of 280
      patients from the French registry. Societe Francaise de Greffe de Moelle.
AB  - High-dose therapy with autologous stem cell transplantation (ASCT) has been
      widely proposed for patients with relapsed Hodgkin's disease (HD). From 1982 to
      1993, we selected (from the French registry for bone marrow transplantation) 280
      patients, who underwent ASCT for relapsed HD after initial treatment including
      chemotherapy. Patient characteristics at diagnosis were: sex ratio (M/F): 1.5;
      median age: 30 years (5-59 years), stage I, II: 43%; III, IV: 57%; 32% had
      chemotherapy, 68% chemo+ radiotherapy. All patients achieved complete remission
      after first-line therapy and subsequently relapsed. The median interval between
      diagnosis and high-dose therapy was 34 months. First relapse occurred in 78% of
      the patients at a median end-of-treatment to relapse time of 18 months. All
      patients received salvage chemotherapy before high-dose therapy, and the median
      time between relapse and high-dose therapy was 5 months. After this regimen, 84%
      of the patients were considered to have chemosensitive relapse. Conditioning
      regimens were: BEAM: 60%; CBV/BEAC: 26%. Transplant-related mortality was 6%.
      With a median follow-up of 3 years after high-dose therapy, overall and
      progression-free survivals at 4 years were 66 and 60%, respectively. Neither the
      conditioning regimen nor the stem cell source affected survival. Good prognostic
      factors for survival were: chemosensitivity of relapse (P < 0.01) and first
      relapse vs further relapse (P < 0.05). For 214 patients in first relapse, other
      significant factors for survival were: end-of-treatment to relapse interval < 12
      months (P < 0.05) and nodal vs extranodal relapse (P < 0.001). These two
      prognostic factors were used to validate a prognostic model with three
      significantly different subgroups: 0 (n = 59), 1 (n = 125), or 2 factors (n = 30)
      with 4-year survival, respectively, at 93, 59 and 43% (P < 0.001). Salvage
      therapy can be tailored in patients with relapsing HD: conventional treatment in
      the good prognosis group (0 factor), high-dose therapy after response to second
      line regimen (1 factor) and more intensive treatments for the bad prognosis group
      (2 factors).

PMID- 9232252
TI  - Photochemical purging of autologous bone marrow grafts: assessment of damage to
      stem cells and the microenvironment in long-term marrow cultures.
AB  - Toxicity of merocyanine 540 (MC540) was assessed in long-term (Dexter-type) bone
      marrow cultures and in a short-term in vitro clonal assay of fibroblast colony
      forming cells (CFU-F). Exposure of freshly explanted mouse bone marrow cells to
      MC540 (15 micrograms/ml) and white light (fluence: 126 kJ/m2) reduced CFU-F by
      approximately 2 logs but did not abrogate the cells' capacity to establish and
      maintain long-term bone marrow cultures. Fat cells were rare or absence in
      adherent layers established with photosensitized bone marrow cells but the
      cultures' capacity to generate non-adherent cells, granulocyte/macrophage
      progenitors (CFU-GM), and early erythroid progenitors (BFU-E) was only moderately
      (28-36%) reduced.

PMID- 9232253
TI  - Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate
      vaccines following autologous peripheral blood stem cell transplantation (PBSCT).
AB  - Accelerated granulocyte and platelet recovery following peripheral blood stem
      cell transplantation (PBSCT) are well documented. We hypothesize that functional
      immunity may also be enhanced in PBSCT and performed a phase II trial of
      immunizations in patients with lymphoma undergoing autologous transplantation
      with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT
      recipients were immunized at 3, 6, 12, and 24-months post-transplantation with
      Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines.
      IgG anti-HIB and anti-TT antibody concentrations were measured and compared
      between the two groups. Geometric mean IgG anti-HIB antibody concentrations were
      significantly higher for PBSCT recipients compared to BMT recipients at 24 months
      post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and
      following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P
      = 0.006). Similar results were noted for IgG anti-TT antibody with significantly
      higher geometric mean antibody concentrations in the PBSCT group at 24 months
      post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039).
      Protective levels of total anti-HIB antibody were achieved earlier in PBSCT
      recipients compared with those of BMT recipients. PBSCT recipients had higher
      antigen-specific antibody concentrations following HIB and TT immunizations.
      These results suggest enhanced recovery of humoral immunity in PBSCT recipients
      and earlier protection against HIB with immunization.

PMID- 9232254
TI  - Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed
      fungal infections in immunocompromised patients with hematologic malignancies.
AB  - Sixty-four adult patients (median age 43) with hematologic malignancies who were
      immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow
      transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B
      lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52)
      or proven (n = 16) fungal infection. The major indications for ABLC were failure
      of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment
      courses in 49 patients comprising 4-58 doses (median 10) were considered
      evaluable. Fourteen courses administered for confirmed infections resulted in
      nine complete and one partial responses, and four failures (71% response). Thirty
      nine empiric courses resulted in 18 complete and six partial responses, and 14
      failures (64% response). The overall response rate was 66%. Five of seven
      evaluable patients with aspergillus pneumonia responded. Response rates were
      comparable for chemotherapy, autograft and allograft recipients. The change in
      serum creatinine from the beginning to the end of therapy was -284 to +277
      mumol/l (median +24). The creatinine doubled during seven evaluable courses of
      therapy, five of which were associated with concomitant nephrotoxic therapy.
      Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal
      dysfunction necessitated discontinuation of ABLC in only four patients. These
      data suggest that ABLC is effective in presumed or confirmed fungal infections in
      immunocompromised patients after transplantation or chemotherapy.

PMID- 9232255
TI  - Antineutrophil cytoplasmic antibodies (ANCA) in chronic graft-versus-host disease
      after allogeneic bone marrow transplantation.
AB  - We studied the usefulness of monitoring antineutrophil cytoplasmic antibodies
      (ANCA) in chronic graft-versus-host disease (cGVHD), a major complication of
      allogeneic bone marrow transplantation. Antigen-specific ELISA and indirect
      immunofluorescence (IIF) were used to search for ANCA in 47 allogeneic bone
      marrow graft recipients who developed cGVHD and in 43 who did not (controls).
      Eight patients exhibited ANCA IIF positivity in the cGVHD group, but none in the
      controls. Specificity was confirmed in antigen-specific assays in only two cGVHD
      patients, both showing antilactoferrin (anti-LF) activity. One of these patients
      was followed-up, and the antilactoferrin antibodies were found only at the time
      of active but limited cGVHD. Among three ANCA IIF-positive patients, two had
      antinuclear autoantibodies and three antineutrophil alloantibodies secondary to
      blood transfusion, which may have been responsible for false ANCA IIF positivity.
      It is concluded that ANCA determination is not useful in patients with cGVHD.
      Polyclonal activation of B lymphocytes could result in ANCA activity during
      cGVHD. False-positive ANCA could be due to allo-immunization following blood
      transfusion. Rare patients may present antilactoferrin antibodies of unknown
      clinical significance.

PMID- 9232256
TI  - Lack of interaction between tacrolimus (FK506) and methotrexate in bone marrow
      transplant recipients.
AB  - Tacrolimus (FK506) is a macrolide lactone effective in the control of graft
      versus-host disease (GVHD). An interaction between high-dose methotrexate and a
      macrolide antibiotic (pristinamycin) leading to prolonged methotrexate exposure
      has been described. Because a randomized prospective trial comparing tacrolimus
      with cyclosporine (both in combination with methotrexate) following allogeneic
      BMT showed the tacrolimus plus methotrexate regimen to be more effective in
      prevention of GVHD, we assessed methotrexate pharmacokinetics in a subgroup of
      the participants of this trial to evaluate the possibility that an interaction of
      FK506 and methotrexate was the explanation for the clinical findings. Mean and
      median methotrexate levels at various time-points after the day 1 and 6
      methotrexate doses were comparable in the tacrolimus and cyclosporine cohorts and
      were elevated in only three of 70 study patients. Area under the curve (AUC)
      concentrations were also similar after the day 1 and 6 methotrexate doses. Thus,
      no significant interaction between tacrolimus and methotrexate is apparent and
      the differences in efficacy between tacrolimus and cyclosporine are unlikely to
      be attributable to pharmacologic interactions with methotrexate.

PMID- 9232257
TI  - Non-tunneled catheters for the collection and transplantation of peripheral blood
      stem cells in children.
AB  - We analyzed the use of non-tunneled (polyurethane, double lumen) central venous
      catheters (CVCs) for the collection, conditioning, transplantation and immediate
      post-transplantation periods in 56 children with various malignant diseases. A
      total of 71 leukaphereses were performed, with a mean of 1.2 apheresis per
      patient, following administration of granulocyte colony-stimulating factor (G
      CSF) using a continuous flow blood cell separator (Cobe Spectra). The mean TBV
      (total blood volume) processed was 4.5 +/- 1.2 s.d. (range 2.4-7). The mean flow
      rate was 30.6 ml/min and the duration of a single apheresis was 327 +/- 84 s.d.
      (range 175-511 min). The mean purities and efficacies of collections were 77.38
      +/- s.d. (range 42-100) and 42.78 +/- s.d. (range 24-80), respectively. The mean
      numbers of mononuclear cells (MNC) and CD34+ cells collected were 9.3 +/- 6.9
      s.d. x 10(8)/kg (range 2-49) and 6.2 +/- 7.2 s.d. x 10(6)/kg (range 1-42),
      respectively. We observed the following complications during catheter insertion
      for collection: pneumothorax (1.7%), mechanical dysfunction (3.5%) that resolved
      with thrombolytic therapy. Complications during conditioning, transplantation and
      immediate post-transplantation periods were entry site infection in five patients
      (8.92%), catheter-related infection in two (3.57%) and catheter-related sepsis in
      three (5.35%). Our results indicate that the collection of PBSC with non-tunneled
      catheters is safe, effective and dis associated with a low incidence of
      complications.

PMID- 9232258
TI  - Imprecision of counting CFU-GM colonies and CD34-expressing cells.
AB  - Determinations of committed haemopoietic progenitor cells, namely CFU-GM (colony
      forming unit-granulocyte/macrophage) and of CD34-expression haemopoietic cells as
      assessed by multiparameter flow cytometry are routine diagnostic tools in
      haemopoietic cell therapy. Generally, the tests are used to optimise the timing
      and management of cytapheresis and to assess the engraftment potential of the
      harvested cells. Both measurements, however, are at best surrogate markers, as an
      adequate routine test which effectively assesses the short- and long-term
      repopulating haemopoietic cell is not available. Nonetheless, cell threshold
      doses have been established. Above these thresholds rapid engraftment is almost
      invariable but below these thresholds the outcome is variable. In this study we
      have focussed on the imprecision in counting haemopoietic cells, as assessed as
      CFU-GM and as CD34-expressing cells. The data on both tests have been analysed
      from six European institutions. The coefficient of variation in CFU-GM colony
      counting was about 30%, whereas the coefficient of variation in flow cytometric
      counting of CD34-expressing cells was about 10%. These data suggest that the
      technical imprecision in enumerating progenitor cells, particularly CFU-GM, at
      low levels, might make a major contribution to the clinical variability observed
      after transplantation of sub-threshold progenitor cell dose.

PMID- 9232259
TI  - Peripheral blood stem cell transplantation in a multiple myeloma patient with end
      stage renal failure.
AB  - Multiple myeloma with IgG kappa monoclonal gammopathy and oliguric renal failure
      requiring hemodialysis was diagnosed in a 49-year-old man. Conventional therapy
      with VAD (vincristin, adriamycin, dexamethasone) failed to induce a complete
      response (CR) but this was subsequently obtained following two cycles of high
      dose intravenous melphalan (70 mg/m2). A relapse occurred 8 months after CR which
      was treated by intensive myeloablative therapy combining total body irradiation
      (6 Gy over 2 days) and high-dose intravenous melphalan (140 mg/m2) followed by
      supportive PBSC transplantation. Hemodialysis was performed every other day
      during the myeloablative therapy and subsequent aplasia. Fluid subtraction
      allowed 1500 Cal/day intravenous alimentation and the only adverse event observed
      was a severe mucositis. A second CR was obtained which lasted 14 months. This
      observation indicates that multiple myeloma patients with end-stage renal failure
      can receive intensive myeloablative therapy without major toxicity.

PMID- 9232260
TI  - Invasive fungal infections in lymphoma patients receiving immunotherapy following
      autologous bone marrow transplantation (ABMT).
AB  - Invasive fungal infections are quite rare (1-5%) following conventional ABMT for
      malignant lymphoma. Two high-risk lymphoma patients (one non-Hodgkin's lymphoma
      (NHL) and one Hodgkin's disease) underwent ABMT followed by immunotherapy as part
      of an experimental therapy given to 12 lymphoma patients aiming to prevent
      relapse following transplantation. The post-immunotherapy course in both patients
      was complicated by invasive fungal infections (pulmonary mucormycosis and
      generalized aspergillosis). The association between invasive fungal infection and
      immunotherapy following ABMT for malignant lymphoma patients is discussed.

PMID- 9232261
TI  - Allogeneic bone marrow transplantation from a donor with severe active rheumatoid
      arthritis not resulting in adoptive transfer of disease to recipient.
AB  - We report a patient who underwent allogeneic bone marrow transplantation from a
      sibling with longstanding untreated severe active rheumatoid arthritis. After 4
      years of follow-up there is no evidence of adoptive transfer of rheumatoid
      arthritis to the recipient. This case, along with another recently reported case,
      provides reassurance that haemopoietic stem cell transplantation from a donor
      with systemic autoimmune disease may not necessarily result in adoptive transfer
      of the disease. All previous reports of transfer of autoimmunity in humans have
      been of organ-specific autoimmune diseases and we speculate that
      pathophysiological differences might account for why systemic autoimmune disease
      is not transferred.

PMID- 9232263
TI  - Additional immunotherapy on the basis of increasing mixed hematopoietic chimerism
      after allogeneic BMT in children with acute leukemia: is there an option to
      prevent relapse?
AB  - The success of allogeneic BMT (allo-BMT) in children with acute leukemias is
      mainly affected by relapse. There is evidence that these patients have only a
      little or no benefit from additional immunotherapy if the treatment is started in
      frank hematological relapse. Recently we were able to demonstrate that pediatric
      patients with acute leukemias and increasing mixed chimerism (MC) post-transplant
      have a significantly enhanced risk of developing relapse. We asked whether there
      is a possibility of preventing relapse, eg by withdrawal of post-transplant
      immunosuppression or by administration of donor lymphocytes in an early phase of
      the development of relapse. We present the case reports of two children (MDS and
      AML) with rapidly increasing MC in whom withdrawal of post-transplant
      immunosuppression or donor lymphocyte infusion (DLI) did prevent relapse.

PMID- 9232262
TI  - Very low-dose methotrexate in the treatment of GVHD in children.
AB  - Acute GVHD is an important clinical problem frequently encountered in relation to
      stem cell transplantation. In its initial treatment glucocorticoids remain the
      established drug of choice. In the face of the side-effects related to therapy
      with glucocorticoids other, possibly less toxic, options for the initial
      treatment of acute GVHD might be of use. We report the successful treatment of
      progressive cutaneous acute GVHD up to grade II in five pediatric recipients of
      unrelated marrow grafts.

PMID- 9232264
TI  - Cyclosporin A/alpha interferon-induced autologous graft-versus-host disease
      following peripheral blood stem cell transplant for chronic myeloid leukaemia: a
      clinico-pathological study.
AB  - Autologous GVHD was induced using CsA and alpha-IFN in a patient undergoing
      autologous PBSCT for accelerated phase CML. We demonstrated that the autologous
      mixed lymphocyte reactions were extremely sensitive and specific for the
      detection of the GVHD when compared to skin biopsy. The resultant autologous GVHD
      was associated with an in vitro GVL effect, suggesting a potential clinical
      benefit of this therapeutic manoeuvre. The post-PBSCT period was associated with
      an improvement in normal haemopoiesis and reduction in the proportion of blood
      cells expressing the Philadelphia chromosome.

PMID- 9232265
TI  - An acute cerebellar syndrome following high-dose chemotherapy and a blood cell
      autotransplant.
AB  - A woman with high-risk stage III breast cancer developed acute cerebellar
      syndrome 75 days after high-dose chemotherapy and blood cell transplant (BCT). An
      extensive search for metastatic, vascular, metabolic, infectious, and
      paraneoplastic etiologies was negative. We postulate a delayed adverse effect of
      high-dose chemotherapy as the etiology.

PMID- 9232266
TI  - Red blood cell depletion and cryopreservation of umbilical cord blood (UCB)

PMID- 9232267
TI  - A Danish pilot study of population-based cord blood sampling.

PMID- 9232268
TI  - Cyclophosphamide 3 g/m2 and G-CSF is an effective and safe outpatient-based PBSC
      mobilising regimen: a single centre experience.

PMID- 9232269
TI  - Gene therapy strategies for carcinoma of the breast.

PMID- 9232270
TI  - Increased hematopoietic progenitor cell maintenance in long-term bone marrow
      cultures containing minimal numbers of contaminating breast cancer cells.
AB  - The maintenance of hematopoietic progenitor cells as assayed in the mixed colony
      (CFU-GEMM) assay in human long-term bone marrow cultures was compared between
      normal allogeneic marrow transplantation donor collections and those from
      candidates for high-dose therapy and autologous bone marrow transplantation
      (ABMT). To be eligible for ABMT, patients were required to have a histologically
      normal appearing bone marrow and therefore any tumor contamination was at minimal
      levels and detectable only after evaluation of the cultured harvests. Marrow from
      15 normal donors, 36 patients with breast cancer, and 30 patients with Hodgkin's
      disease was evaluated. The number of mononuclear cells placed in culture was
      standardized. In all groups, significantly more progenitor cells were recovered
      at 4-6 weeks of culture that at 12-14 weeks. At 4-6 and 12-14 weeks, there were
      no significant differences in the number of progenitor cells recovered from the
      cultures of normal donors and tumor negative cultures of breast cancer or
      Hodgkin's disease patients. However, following 4-6 and 12-14 weeks of culture,
      progenitor cell numbers of cultures which contained breast cancer cells were
      significantly higher than the pooled values for cultures from the concurrent
      normal controls, and those from breast cancer and Hodgkin's disease patients with
      tumor negative cultures. These results suggest that minimal breast cancer cell
      contamination of the bone marrow can influence the production of marrow
      progenitor cells. Exposure to prior chemotherapy or radiation therapy does not
      appear to be the cause of this effect. The most likely mechanism is the local
      production of cytokines by the tumor cells, although a process involving direct
      adhesive contact of the tumor cells with hematopoietic cells, which is sometimes
      observed in semisolid cultures, cannot be excluded.

PMID- 9232271
TI  - The expression of Ki-S1 and BCL-2 and the response to primary tamoxifen therapy
      in elderly patients with breast cancer.
AB  - Ki-S1, a marker of proliferation, and bcl-2, the gene product of which is an
      antagonist of apoptosis, have been measured in 51 ER-positive primary breast
      cancers before and during tamoxifen treatment and then related to clinical
      response. Both markers were detected in the majority of tumours before treatment
      and, quantitatively, initial expression of Bcl-2 protein, but not Ki-S1, was
      significantly related to the percentage reduction in tumour volume as assessed by
      ultrasound. Staining for both markers was lower in post treatment samples than in
      those taken prior to treatments, but concordant decreases in staining indices
      were seen in only 11 of the 51 tumours. The results demonstrate, using clinical
      material, that the response to tamoxifen may involve changes in proliferation
      and/or susceptibility to cell-death.

PMID- 9232272
TI  - Weight gain associated with adjuvant tamoxifen therapy in stage I and II breast
      cancer: fact or artifact?
AB  - There is a perception that tamoxifen causes weight gain in breast cancer
      patients. The purpose of this research study was to determine if weight gain is
      associated with tamoxifen therapy and to observe the impact of weight gain on
      recurrence and survival. Prognostic indicators, changes in weight, and disease
      status from diagnosis to the end of treatment were studied in 200 consecutive
      Stage I and II breast cancer patients, not receiving systemic chemotherapy,
      admitted from 1986 to the present, with observation periods ranging from 3-5
      years. A mean weight gain of 1.2 Kgs was seen in all patients; however, weight
      gain was not significantly different for those receiving tamoxifen vs. those not
      receiving tamoxifen, (P = 0.66, CI 95% for the difference -1.8 Kgs to +1.2 Kgs).
      Weight gain during treatment with tamoxifen was not correlated with treatment
      duration or with recurrence or survival. Age at diagnosis was positively
      correlated to weight gain in all groups. Our data failed to show that tamoxifen
      is associated with weight gain. The moderate weight gain observed in this patient
      population is comparable to the general aging disease-free population and may no
      be treatment-related. These findings may help to alleviate some concerns of both
      physicians and patients when tamoxifen is the drug of choice for adjuvant
      therapy.

PMID- 9232273
TI  - A point mutation in the human estrogen receptor gene is associated with the
      expression of an abnormal estrogen receptor mRNA containing a 69 novel nucleotide
      insertion.
AB  - A novel ER-like mRNA containing a 69 nucleotide insertion precisely between exon
      5 and 6 sequences was previously identified in human breast cancer biopsy
      samples. Data are presented which suggest that the 69 nucleotide sequence is
      normally present in intron 5 of the human estrogen receptor gene. The region
      corresponding to and surrounding this 69 nucleotide sequence was cloned and the
      nucleotide sequence determined. Cloning and sequencing of the corresponding
      region in genomic DNA isolated from a breast tumor expressing the 69 nucleotide
      inserted ER mRNA, revealed an A-->G point mutation immediately 3' to the 69
      nucleotide sequence. This point mutation resulted in the generation of a
      consensus splice donor site. A consensus splice acceptor site sequence is
      normally present immediately 5' to the 69 nucleotide sequence. These data are
      consistent with the 69 nucleotide sequence being recognized as an exon by the
      splicing machinery, and resulting in processing of a mature ER mRNA containing
      the 69 nucleotide insert.

PMID- 9232274
TI  - Isolation and analysis of different subpopulations of normal human breast
      epithelial cells after their infection with a retroviral vector encoding a cell
      surface marker.
AB  - The use of gene transfer procedures has greatly facilitated the investigation of
      cell lineage relationships and other developmental processes in a variety of
      primary tissues. In this report we described the infection and selection of
      primary human breast epithelial cells using retroviral vectors (Jzen-HSA-NEO and
      MSCV-HSA.NEO) containing the complete 228 bp coding sequence of a murine cell
      surface marker (Heat Stable Antigen, HSA) as well as the neomycin resistance
      (neo(r)) gene. Expression of the transduced HSA gene was detectable using either
      flow cytometry or immunohistochemistry after staining cells with an anti-murine
      HSA-specific antibody (M1/69). Expression of the transduced neo(r) gene conferred
      resistance to G418. In initial experiments with the MCF-7 breast cancer cell
      line, continued expression of both markers was demonstrated in a high proportion
      of cells for at least 4 weeks after their infection by positive M1/69 staining of
      cells that had been selected by prior incubation in G418. Evidence of gene
      transfer to early stage (< 9 days old) primary cultures of normal human breast
      epithelial cells (15 experiments with cells from 12 normal individuals) was also
      obtained using an infection protocol in which these calls were exposed to helper
      free viral supernatants (2 incubations, 4 to 6 hr each) after being subcultured
      for 12 to 18 hr to increase their rate of proliferation. The presence of 5-50%
      (mean = 26%) HSA+ cells was demonstrated in these experiments within 5 days after
      their infection and the HSA+ populations included both myoepithelial and luminal
      phenotypes. The transduced (HSA+) cells within both of these subpopulations could
      also be separately isolated by FACS and subcultured. These results should provide
      an important starting point for future studies of genetically modified or marked
      primary human breast epithelial cell populations.

PMID- 9232276
TI  - MRI in patients with axillary metastases of occult breast carcinoma.
AB  - In 4 women with adenocarcinoma metastasis in an axillary lymph node and no
      primary tumor found, we investigated whether Magnetic Resonance Imaging (MRI) of
      the breast could detect a clinically and mammographically occult breast tumor.
      MRI detected an enhancing lesion in 3 women and an enhancing double lesion in one
      patient. MRI directed ultrasound guided fine needle aspiration cytology confirmed
      the 5 breast carcinomas in the 4 women. In women with metastasis in an axillary
      lymph node consistent with breast cancer and without a primary tumor, MRI of the
      breast should added to clinical examination and mammography before defining it as
      an occult primary and planning therapy.

PMID- 9232275
TI  - Prognostic factors for metachronous contralateral breast cancer: a comparison of
      the linear Cox regression model and its artificial neural network extension.
AB  - The purpose of the present study was to assess prognostic factor for metachronous
      contralateral recurrence of breast cancer (CBC). Two factors were of particular
      interest, namely estrogen (ER) and progesterone (PgR) receptors assayed with the
      biochemical method in primary tumor tissue. Information was obtained from a
      prospective clinical database for 1763 axillary node-negative women who had
      received curative surgery, mostly of the conservative type, and followed-up for a
      median of 82 months. The analysis was performed based on both a standard (linear)
      Cox model and an artificial neural network (ANN) extension of this model proposed
      by Faraggi and Simon. Furthermore, to assess the prognostic importance of the
      factors considered, model predictive ability was computed. In agreement with
      already published studies, the results of our analysis confirmed the prognostic
      role of age at surgery, histology, and primary tumor site, in that young patients
      (< or = 45 years) with tumors of lobular histology or located at inner/central
      mammary quadrants were at greater risk of developing CBC. ER and PgR were also
      shown to have a prognostic role. Their effect, however, was not simple in
      relation to the presence of interactions between ER and age, and between PgR and
      histology. In fact, ER appeared to play a protective role in young patients,
      whereas the opposite was true in older women. Higher levels of PgR implied a
      greater hazard of CBC occurrence in infiltrating duct carcinoma or tumors with an
      associated extensive intraductal component, and a lower hazard in infiltrating
      lobular carcinoma or other histotypes. In spite of the above findings, the
      predictive value of both the standard and ANN Cox models was relatively low, thus
      suggesting an intrinsic limitation of the prognostic variables considered, rather
      than their suboptimal modeling. Research for better prognostic variables should
      therefore continue.

PMID- 9232277
TI  - International bioethics at the bedside.

PMID- 9232278
TI  - The impact of risk factors and pre-existing conditions on the mortality of burn
      patients and the precision of predictive admission-scoring systems.
AB  - Clinical experience has shown that concomitant diseases and risk factors have a
      significant influence on the patient's outcome. Since none of the currently
      available score systems consider the impact of concomitant diseases or risk
      factors on burn trauma mortality, the present study was planned to further
      evaluate the role of these factors. Four hundred and ninety-eight patients could
      be included in this retrospective analysis of prospectively collected data.
      Parameters documented were: sex, age, weight, height, laboratory data, TBSA,
      inhalation trauma (IHT), full thickness (3 degrees) burn and pre-existing
      conditions. Single-variable analysis (SVA), logistic regression and CART analysis
      were performed. The data confirm the role of age and TBSA as the strongest
      prognostic variables. Chronic alcohol abuse and smoking, IHT and pre-existing
      cardiac and neurologic conditions were also found to be significant. Borderline
      groups could be identified in the ABSI score (7-10), where the risk factors cause
      'mortality-shifting'. It can be concluded that risk factors and pre-existing
      conditions have a significant impact on the prognosis of burn mortality and
      should be incorporated into further refinements of burn admission scores.

PMID- 9232279
TI  - Skin replacement by cultured keratinocyte grafts: an Australian experience.
AB  - We have prepared and supplied cultured epithelial autografts (CEA) to treat 37
      burn patients around Australia. The method is a modification of the original
      methods of Green et al. The confluent 75 cm2 secondary cultures, obtained after
      less than 3 weeks, are 8-10 cell layers thick after detachment and have a
      shrinkage of only 7-14 per cent. The patients had full-thickness skin loss to 55
      95 per cent of their total body surface area (TBSA) or deep partial-thickness
      burns to 3-50 per cent TBSA owing to scald injuries. In the case of full
      thickness burns the CEA take in the 17 surviving patients for which data was
      available averaged 53 per cent (range 10-100 per cent). The take for seven
      patients with partial-thickness burns averaged 73 per cent (range 25-100 per
      cent). The variability and early graft failure is attributed largely to the
      presence of infection. The durability and percentage take of CEA grafts is
      discussed together with future developments in the replacement of both dermis and
      epidermis in burns injury.

PMID- 9232280
TI  - Effect of burn patient serum on fibroblast and keratinocyte cell morphology.
AB  - The effect of burn patient serum on fibroblast and keratinocyte cell morphology
      in culture was investigated using the scanning electron microscope. Serum was
      taken from five patients with burn injuries ranging from 8 to 65 per cent TBSA
      (10-65 per cent full-thickness). One patient had superficial burns. Pooled serum
      from 23 volunteers was used as the control serum. The cells were seeded onto
      collagen-coated glass coverslips and incubated for 5 days with culture medium
      containing 10 per cent (v/v) control serum or patient serum taken during the
      early postburn period. Scanning electron micrographs demonstrated a reduction in
      fibroblast cell density with serum from patients with full-thickness burns.
      Furthermore, the spindle shape of the fibroblast cell was greatly exaggerated
      compared with control cultures. The integrity of the keratinocyte sheet was
      destroyed when keratinocyte cells were incubated with serum fron patients with
      full-thickness burns. Globular-like structures or membrane protrusions were
      present in concentrated areas on keratinocyte cells which were not present in
      control cultures. This study demonstrated the vulnerability of cutaneous cells to
      systemic factors present in the early postburn serum. The extent of the effect
      appears to be related to the presence of full-thickness injury. This effect may
      further explain the frequent aberrant wound healing response to burn injury.

PMID- 9232281
TI  - Evolution and significance of circulating procalcitonin levels compared with IL
      6, TNF alpha and endotoxin levels early after thermal injury.
AB  - To determine the evolution and significance of circulating procalcitonin (ProCT),
      IL-6 TNF alpha and endotoxin levels early after thermal injury, we performed a
      prospective, single unit, longitudinal study. Forty burn patients with total body
      surface area (TBSA) > 30 per cent were studied, of whom 33 suffered an inhalation
      injury. Blood samples were taken on the day of admission, every 4 h during the
      first day and daily during the first week. All patients had increased ProCT and
      IL-6 levels without any proven infection. Endotoxin and TNF alpha levels remained
      very low or undetectable. ProCT and IL-levels correlated well with the severity
      of skin burn injury (respectively, p < 0.006 and p < 0.028, using the non
      parametric Kruskal-Wallis test). ProCT levels are not associated with smoke
      inhalation. ProCT and IL6 are prognostic factors of mortality at the time of
      admission but less reliable than the clinical UBS (unit burn standard) score.
      Endotoxin and TNF alpha were undetectable, suggesting that the problem of the
      early gut bacterial translocation remains to be proven.

PMID- 9232282
TI  - The use of aztreonam as an alternate therapy for multi-resistant Pseudomonas
      aeruginosa.
AB  - The emergence of multi-resistant Gram-negative bacteria has created a most
      alarming clinical situation. The armamentarium of antibiotics used against this
      group of organisms is rapidly being depleted. Our routine therapeutic approach to
      control and prevent these Gram-negative bacteria from gaining a foothold was the
      empirical use of an aminoglycoside combined with piperacillin. However,
      aminoglycoside resistance is now routine rather than unusual. We evaluated the
      role of the monobactam aztreonam in burn wound infections and compared it to the
      aminoglycosides amikacin and gentamicin as well as piperacillin for the
      Enterobacteriacae and Pseudomonas aeruginosa. A total of 1274 Gram-negative
      isolates including P. aeruginosa were evaluated for susceptibility to the above
      mentioned antibiotics from January 1995 to August 1995 (Table I). Among the
      Enterobacteriacae, aztreonam was more effective than amikacin and piperacillin
      (58.4 per cent vs. 45.8 per cent, respectively). However, it still fluctuated
      among the Enterobacteriacae as did the aminoglycosides. One major significant
      finding was that while susceptibility to aztreonam was variable for the
      Enterobacteriacae, P. aeruginosa remained 90 per cent susceptible to aztreonam
      and 90 per cent susceptible to piperacillin, whereas it was 79 per cent resistant
      to the aminoglycosides. Consequently, when choosing an antimicrobial in a
      suspected P. aeruginosa burn wound infection, aztreonam and piperacillin should
      be considered as the first line of defense.

PMID- 9232283
TI  - Can superoxide dismutase prevent postburn dermal ischemia?
AB  - Decreasing progressive dermal ischemia after burning could theoretically limit
      the amount of skin necrosis. It is controversial whether the use of free radical
      scavengers could prevent the progressive dermal ischemia of the postburn stasis
      zone. We evaluated the effect of superoxide dismutase (SOD) on preventing
      postburn dermal ischemia in animal models by the India ink perfusion and skin
      transparent preparation techniques. The closely clipped backs of guinea-pigs were
      bathed in 75 degrees C water for 10 s. Within 5 min postburn, SOD-treated groups
      were administered SOD (10,000 u/kg) intra-peritoneally every 6 h. All animals
      were perfused with 70 per cent India ink via cervical artery cannula by 16 kPa
      constant pressure at 0, 8, 16, 24 h postburn, and the skin transparent
      preparations were made, while the level of malonyl dialdehyde (MDA) in skin
      tissue was assessed. The results showed that with prolongation of postburn time,
      the rate of filling of India ink in skin capillary plexuses decreased gradually
      (p < 0.01). MDA increased continuously, which was related to postburn dermal
      ischemia (r = 0.689, p < 0.01). Though the level of MDA decreased in SOD-treated
      groups, the India ink filling rates showed no significant difference between
      controls and experimental groups (p > 0.05). The results were also confirmed by
      observation of skin transparent preparations and TEM. This study suggests that
      superoxide dismutase fails to prevent progressive dermal ischemia after burning.

PMID- 9232284
TI  - Effect of a prostaglandin I2 analogue, beraprost sodium, on burn-induced gastric
      mucosal injury in rats.
AB  - Stress ulcers still have a high mortality in critically burned patients and the
      pathophysiology remains relatively unknown. Impaired gastric mucosal perfusion is
      one of the factors contributing to gastric mucosal ulceration. Burn injury causes
      thrombosis and vascular occlusion by increasing the blood viscosity, resulting in
      decreased organ perfusion. Reduced blood flow is one of the most important
      factors in gastric mucosal ulceration. Beraprost sodium is a chemically stable
      prostaglandin I2 (PGI2) analogue with antiplatelet, vasodilator and
      cytoprotective actions. In the present study, we examined the effects of a PGI2
      analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan)
      on burn-induced gastric mucosal changes in rats. Twenty male Sprague-Dawley rats
      weighing an average of 400 g were burned with hot water (90 degree C) and then
      divided into two groups of 10 animals. One group received 0.015 mg of beraprost
      sodium intraperitoneally immediately after burn injury, while the control group
      received the same volume of saline. Gastric mucosal blood flow was measured with
      a laser Doppler flowmeter and the area of mucosal necrosis was also determined
      macroscopically and histologically. Gastric mucosal damage was significantly
      reduced in the beraprost sodium-treated rats and gastric mucosal blood flow was
      significantly improved (p < 0.05). These findings demonstrate that PGI2 plays a
      very important role in the pathophysiology of burn-induced Curling's ulcer and
      that beraprost sodium can improve gastric mucosal blood flow and reduce mucosal
      damage.

PMID- 9232285
TI  - Treating mass burns in warfare, disaster or terrorist strikes.

PMID- 9232286
TI  - Failure of therapeutic ultrasound in healing burn injuries.
AB  - Experimental observations suggest that therapeutic ultrasound stimulates wound
      healing. Despite the controversy concerning its efficiency, this procedure is
      commonly implemented. To study the effect of this treatment in burns, we
      conducted a randomized control trail in 20 Fischer rats. Two groups of 10 animals
      each were studied, In group 1 the experimental burn was treated with pulsed
      ultrasound (SATA 0.25 W/cm2), in group 2 with continuous ultrasound (0.3 W/cm2).
      No stimulating effect of ultrasound could be demonstrated in these two groups,
      monitored by histological examination and a size index. These results discourage
      the clinical administration of therapeutic ultrasound to enhance the healing of
      burns.

PMID- 9232287
TI  - Temperature profiles during resuscitation predict survival following burns
      complicated by smoke inhalation injury.
AB  - Temperature and resuscitation profiles of 15 non-survivors were compared with
      matched survivors of major burns. All patients were intubated and ventilated for
      smoke inhalation injury, survived more than 3 days postburn and had a cutaneous
      burn greater than 15 per cent of the body surface area (mean 32.3 +/- 11.0 per
      cent SD). Cases were matched for similar ages (within 10 years) and total body
      surface area burn (within 10 per cent). The rate of core temperature rise
      following admission to the burn unit was significantly greater in survivors (mean
      0.46 +/0 0.18 degree C/h) compared with matched non-survivors (mean 0.30 +/- 0.15
      degrees C/h; p < 0.01). Core temperature increased at a rate of 0.27 degrees C/h
      or greater in all survivors, whereas 7 non-survivors raised their core
      temperature at a rate less than this. The rate of skin temperature rise was also
      significantly greater in the survivors (mean 1.35 +/- 0.91 degrees C/h) compared
      with matched non-survivors (mean 0.63 +/- 0.43 degrees C/h, p < 0.01). In 13/15
      survivors, the skin temperature increased at a rate of 0.6 degree C/h or greater,
      whereas in 8/15 non-survivors skin temperature increased at a rate less than
      this. There was a negative relationship between initial core temperature and
      delay from time of burn to admission to the burns unit in non-survivors
      (correlation coefficient = -0.92; p < 0.01), whereas there was no effect of delay
      in the survivors. These findings suggest that patients with a high mortality
      probability can be detected early in their clinical course by means of
      temperature profiles.

PMID- 9232288
TI  - Complications in the use of diathermy.
AB  - Electrical burns in diathermy rarely occur but are not always recognized as such
      or thoroughly investigated. The literature has proved to be very sparse in terms
      of reference to complications, although prolonged courses of treatment are
      required in individual cases. This paper analyses and discusses the problems of
      burns associated with diathermy that occurred in seven patients.

PMID- 9232289
TI  - Laryngeal fistula following electrical burn.
AB  - A rare case of electrical burn resulting in laryngeal fistula is presented. The
      fistula manifested about 3 weeks postburn. This was successfully managed by using
      a pectoralis major myocutaneous flap. A 1 year follow-up of the patient is
      presented.

PMID- 9232290
TI  - Severe burns resulting from an exploding teat on a bottle of infant formula milk
      heated in a microwave oven.
AB  - Accidental injury to infants can result from the use of home microwave ovens. The
      spectrum of injury includes scald burns of the trachea, palate oropharynx and
      oesophagus due to aspiration and ingestion of foods that have been overheated.
      There is one previous case report of a child with second-degree burns of 6 per
      cent of his body area due to explosion of the plastic liner and nipple on a
      feeding bottle top. We present a case report of an infant who suffered 7 per cent
      full-thickness burns following explosion of the bottle teat and subsequent
      splattering with hot milk. He required mid-palmar amputation of his left hand
      including thumb, index and middle fingers. The full-thickness burns of left cheek
      and left shoulder were grafted but will result in significant scarring. It is
      common practice in many homes to heat infant feeds in the microwaves. We suggest
      that health professionals dealing with children need to be aware of the potential
      hazards so that appropriate education of parents can take place.

PMID- 9232291
TI  - Suicide attempted by burning in Brazil.
AB  - From 1984 through 1995, a total of 82 patients were admitted to the Burn Center
      of the University Hospital of Ribeirao Preto, University of Sao Paulo with a
      history of attempted suicide. Fifty-eight patients were female and 24 were male.
      The mean burned surface area (BSA) was 52.4 per cent and the mortality rate was
      44 per cent. Methyl alcohol was used by 87.5 per cent of the patients to ignite
      the fire.

PMID- 9232293
TI  - Recent references.

PMID- 9232294
TI  - Should we reassess the susceptibility of MH patients?

PMID- 9232292
TI  - Is the psoriatic skin of burn patients suitable for split-thickness skin
      autograft?

PMID- 9232295
TI  - Human immunodeficiency virus and health care workers: risking livelihood as well
      as life.

PMID- 9232296
TI  - Clinical reassessment of malignant hyperthermia in Abitibi-Temiscamingue.
AB  - PURPOSE: In 1992, 1812 individuals (1.2% of the population) were labelled at risk
      for malignant hyperthermia (MH) in seven families from Abitibi-Temiscamingue. To
      evaluate the effective risk in this population, a multidisciplinary study was
      undertaken which included clinical, genealogical and molecular aspects. This
      paper presents the clinical aspects of the study. METHOD: For each of the 1546
      individuals reached, all anesthetic exposures were screened for elements relevant
      to MH. Malignant hyperthermia events were analyzed with "the clinical grading
      scale." All 44 reports of caffeine halothane contracture tests were reappraised.
      Finally, genealogical study was done to complete each family tree up to the
      initial French settlers in order to identify links between these seven families
      through common ancestors. RESULTS: Following this reassessment, the families were
      compared and classified into four groups. Two families (1097 individuals) are not
      considered to be at a higher risk for MH than the population in general. Two
      families are still considered possibly at risk. Finally, one family (402
      individuals) is highly at risk and two other families are probably at risk.
      Family trees did not show any link up to the colonization of Abitibi
      Temiscamingue in the beginning of this Century but common ancestors were found
      around the 9th generation. CONCLUSION: This clinical reassessment will help to
      focus education and prevention on a much smaller group of individuals still
      considered potentially at risk for MH. By adequate evaluation of phenotypes,
      combined with the use of a genealogical approach, it will be possible to target
      families for molecular research.

PMID- 9232297
TI  - Patient-controlled epidural analgesia after caesarean section using meperidine.
AB  - PURPOSE: To determine the effects of the addition of a background infusion to
      patient-controlled epidural analgesia (PCEA) using meperidine for analgesia after
      Caesarean section. METHODS: In a randomized, double-blind study, we assigned 40
      patients having elective Caesarean section to receive postoperative analgesia by
      patient-controlled epidural analgesia (PCEA) using meperidine 5 mg.ml-1 with
      (group Pi) or without (group Po) a background infusion of 10 mg.hr-l. The PCEA
      settings (20 mg bolus, 10 min lockout interval, four-hour maximum dose 150 mg)
      were otherwise identical. We compared pain at rest, pain on coughing, side
      effects, number of PCEA demands, drug consumption and patient satisfaction
      between groups in the first 24 hr after surgery. RESULTS: Total consumption of
      meperidine was greater in group Pi (median 390 mg) than in group Po (median 240
      mg; P = 0.017) and the number of PCEA demands was greater in group Po (median 12)
      than in group Pi (median 7.5; P = 0.012). Analgesia, side effects and patient
      satisfaction was similar between groups. CONCLUSION: Addition of a background
      infusion to PCEA using meperidine after Caesarean section has no clinical
      benefit.

PMID- 9232298
TI  - Comparative topical anaesthesia of EMLA and liposome-encapsulated tetracaine.
AB  - BACKGROUND: The eutectic mixture of local anaesthetics (EMLA) provides effective
      topical anaesthesia after a minimum of 60 to 90 min application. Since liposome
      encapsulated tetracaine (LET) can provide rapid dermal penetration, the goal of
      this study was to compare the local anaesthetic effects of EMLA and LET in human
      volunteers after 60 min application. METHODS: After obtaining institutional
      approval and informed consent, healthy volunteers were recruited in a double
      blind, crossover, randomized trial. The study creams (0.5 ml EMLA and 0.5 ml LET
      5%) were applied randomly to opposite arms for 60 min. The discomfort of i.v.
      catheterization was assessed using a visual analogue pain score (VAS). Cutaneous
      side effects of the creams were recorded. RESULTS: Sixty-one subjects were
      studied. Twenty-one were excluded because of technical difficulties. Forty
      subjects completed the study and were included in the data analysis. The mean (
      +/- SD) VAS was lower for LET than for EMLA (10.9 +/- 9.0 mm vs 22.7 +/- 17.1 mm,
      P < 0.001). Erythema secondary to vasodilatation occurred more frequent in the
      LET group than in the EMLA group (33 vs 3, P < 0.001). One subject with a history
      of atopy developed a rash at the LET application site. CONCLUSION: Liposome
      encapsulated tetracaine can provide a more effective topical anaesthesia than
      EMLA for intravenous catheterization after 60 min application. Clinical
      evaluations are necessary to determine the efficacy and safety of LET in
      providing topical anaesthesia for various invasive percutaneous procedures in
      other patient populations.

PMID- 9232299
TI  - Monitoring orbicularis oculi predicts good intubating conditions after vecuronium
      in children.
AB  - PURPOSE: The aim of the study was to compare visual estimation of onset of
      neuromuscular blockade at both the adductor pollicis (AP) and the orbicularis
      oculi (OO) in children and to determine if monitoring the OO could predict good
      intubating conditions during vecuronium-induced neuromuscular blockade. METHODS:
      Thirty ASAI--II children (1.5-9 yr) were studied. Anaesthesia was induced with 6
      8 mg.kg-1 thiopentone. The ulnar nerve at the wrist and the temporal branch of
      the facial nerve were stimulated every 10 sec using train-of-four (TOF) stimuli.
      Vecuronium, 0.15 mg.kg-1, was administered as a bolus. The responses at both the
      OO and the AP were evaluated visually. Patients were randomly divided into two
      groups. In the AP group (n = 15), the trachea was intubated when the AP was
      completely blocked. In the OO group (n = 15), intubation was performed when the
      OO was completely blocked. Intubating conditions were scored on a scale of 1 to
      4. RESULTS: All the patients had complete blockade at both the orbicularis oculi
      and the adductor pollicis. In the two group, time from injection of vecuronium to
      complete neuromuscular blockade was shorter at the orbicularis oculi than at the
      adductor pollicis, 1.5 +/- 0.5 min vs 2.3 +/- 0.7 min, respectively, (P < 0.05;
      mean +/- SD) in the AP group, 1.7 +/- 0.3 min vs 2.3 +/- 0.8 min, respectively in
      the OO group (P < 0.05). Intubating conditions were excellent in all patient
      except one, where it was rated as good. They did not differ between groups.
      CONCLUSION: Following administration of 0.15 mg.kg-1 vecuronium in children,
      monitoring of the OO can detect good intubating conditions 0.7 min earlier than
      with monitoring of the AP.

PMID- 9232300
TI  - Reduction in post-intubation respiratory resistance by isoflurane and albuterol.
AB  - PURPOSE: This study examined the bronchodilating effects of 0.6 MAC and 1.1 MAC
      isoflurane (ISF) on respiratory system resistance (Rrs) following tracheal
      intubation and determined whether albuterol supplements that effect. METHODS:
      Sixty-seven adult patients were anaesthetized with 2 micrograms.kg-1 fentanyl and
      5 mg.kg-1 thiopentone and their tracheas intubated following administration of 1
      mg.kg-1 succinylcholine. Respiratory system resistance was measured following
      intubation and the patients then randomized to receive either 1.1 MAC ISF in
      oxygen or 0.6 MAC ISF in 50% nitrous oxide and oxygen. Ten minutes later, Rrs was
      again measured. Patients were then further randomized to receive albuterol or a
      placebo using incremental doses of 2, 5, and 10 puffs (albuterol puff = 90
      micrograms) delivered via a metered dose inhaler at ten minute intervals.
      RESULTS: Isoflurane at 1.1 MAC decreased post-intubation Rrs by 23 +/- 5% (mean
      +/- sem) whereas the decrease was only 7 +/- 5% for 0.6 MAC ISF (P < 0.01). Two
      puffs of albuterol resulted in a further decrease of 12 +/- 3% (mean +/- sem) in
      Rrs compared with a 2 +/- 4% decrease in the placebo groups (P < 0.05).
      Additional puffs of albuterol resulted in no further changes in Rrs. CONCLUSION:
      We conclude that following tracheal intubation the reduction in Rrs produced by
      ISF is highly concentration dependent. Albuterol results in a small further
      reduction in Rrs.

PMID- 9232301
TI  - Premedication with midazolam is more effective by the sublingual than oral route.
AB  - PURPOSE: This study compared the sedative effects of sublingual tablet midazolam
      (Roche Dormicum 7.5 mg) with the oral route as premedication. METHODS: One
      hundred ASA physical status I and II gynaecological patients were randomly
      selected to receive a 7.5 mg tablet of midazolam either sublingually or orally as
      premedication about one hour before elective surgery. There were 50 patients in
      each group. The degree of sedation was assessed according to the Ramsay scale
      initially and then at 20, 30, 45 and 60 min intervals by a second observer
      blinded to the route of administration. The time for complete drug dissolution
      was studied in the sublingual group by the inspection of tablet residue under the
      tongue every five minutes for 20 min, then the patients were interviewed
      regarding their acceptance of taste. RESULTS: The sedation scores in the
      sublingual group were higher than in the oral group at 30 and 60 min after drug
      administration. (P = 0.0054 and P = 0.008) Seventy-two percent of the sublingual
      group had complete drug dissolution within 10 min and 64% of the patients in the
      sublingual group found the tablet acceptable with regard to its taste.
      CONCLUSION: Midazolam 7.5 mg sublingual is a more effective pre-anaesthetic
      sedative than by the oral route.

PMID- 9232302
TI  - Treatment of acute respiratory failure by prolonged non-invasive ventilation in a
      child.
AB  - PURPOSE: To evaluate the feasibility and the efficacy of non-invasive ventilation
      (NIV) by nasal mask in a paediatric patient. CLINICAL FEATURES: A four-year-old
      girl with acute lymphocytic leukaemia (ALL L1, pre-pre B) complicated by acute
      respiratory failure was treated with NIV. ON admission she exhibited hyperpyrexia
      (40C), pancytopaenia and severe hypoxia with hypocapnia (PaO2 = 45 mmHg; PaCO2 =
      28.2 mmHG; pH = 7.30; SpO2 = 76%; ABE = -7.3 mmol.L-1. With NIV, PaO2 improved
      (PaO2 = 78 +/- 8 mmHG; SpO2 = 86 +/- 2; PaCO2 = 39 +/- 2) throughout the first
      day. Treatment was continued for six days until the patient was discharged. No
      complications were recorded. CONCLUSION: Non-invasive ventilation by nasal mask
      may represent a choice in the treatment of acute respiratory failure of
      parenchymal origin in paediatric haematological patients.

PMID- 9232303
TI  - Brainstem anaesthesia after peribulbar anaesthesia.
AB  - PURPOSE: To present a case of brainstem anaesthesia as a complication of
      peribulbar anaesthesia. CLINICAL FEATURES: A 75-yr-old woman received peribulbar
      anaesthesia for cataract surgery. A few seconds after the block performed, she
      had a respiratory arrest, became unconscious, and developed hypertension and
      tachycardia followed by hypotension and bradycardia. Ventilatory and haemodynamic
      support were performed before the patient regained adequate spontaneous
      breathing, and normal heart rate and blood pressure. CONCLUSION: Peribulbar
      anaesthesia generally carries a low risk of serious complications. However,
      respiratory arrest and brainstem anaesthesia may occur as complications of
      peribulbar blocks.

PMID- 9232304
TI  - Recombinant tissue type plasminogen activator treatment of thrombosed mitral
      valve prosthesis during pregnancy.
AB  - PURPOSE: Prosthetic heart valve thrombosis occurring during pregnancy is a life
      threatening complication. Surgical treatment requires clot removal under
      cardiopulmonary bypass (CPB) and carries a high mortality. We describe the
      successful use of thrombolytic therapy for recurrent thrombosed valve prosthesis
      in a pregnant patient. CLINICAL FEATURES: A 32-yr-old patient whose pregnancy was
      complicated by two episodes of a thrombosed St Jude mitral prosthesis is
      reported. The first episode occurred at 20 wk of pregnancy during the change of
      oral anticoagulant therapy (acenocoumarol 4 mg a day) to sc heparin. As the
      patient was in cardiogenic shock, the valve thrombus was treated by clot removal
      under CPB., with a cross clamp time of 32 min, a perfusion pressure above 70
      mmHG. There was no fetal cardiac rhythm during CPB which lasted < 45 min. The
      second episode occurred at the 28th gestational week in a patient in cardiogenic
      shock and because reoperation was thought to carry too high a risk, the thrombus
      was successfully treated with 50 mg recombinant tissue plasminogen activators
      (rtPA) i.v. Following this, the course of pregnancy was uneventful and carried to
      term and the patient delivered vaginally. Pain relief was achieved with
      intravenous patient-controlled analgesia with alfentanil (bolus 100 mug; lock out
      = five minutes). Although rtPA has been used before, this is the first report in
      which pregnancy was carried to term and standard vaginal delivery performed.
      CONCLUSION: This case provides evidence for the efficacy and relative safety of
      rtPA as thrombolytic therapy in the treatment of haemodynamically compromised
      valve heart thrombosis in pregnancy.

PMID- 9232305
TI  - Non-invasive quantification of diaphragm kinetics using m-mode sonography.
AB  - PURPOSE: The standard conditions of spirometry (i.e., wearing a noseclip and
      breathing through a mouthpiece and a pneumotachograph) are likely to alter the
      ventilatory pattern. We used "time motion" mode (M-mode) sonography to assess the
      changes in diaphragm kinetics induced by spirometry during quiet breathing.
      METHODS: An M-mode sonographic study of the right diaphragm was performed before
      and during standard spirometry in eight patients without respiratory disease (age
      34 to 68 yr). RESULTS: During spirometry, the diaphragm inspiratory amplitude
      (DIA) increased from 1.34 +/- 0.18 cm to 1.80 +/- 0.18 cm (P = 0.007), whereas
      the diaphragmatic inspiratory (T1 diaph) increased from 1.27 +/- 0.15 to 1.53 +/-
      0.23 sec, (P = 0.015, without change in diaphragmatic total time interval (Ttot
      diaph). Therefore, the diaphragm duty cycle (T1 diaph/Ttot diaph) increased from
      38% +/- 1% to 44% +/- 4% (P = 0.023). The diaphragm inspiratory (DIV) and
      expiratory (DEV) motion velocity (P = 0.007). CONCLUSION: M-mode sonography
      enabled us to demonstrate that the wearing of a nose clip and breathing through a
      mouthpiece and a pneumotachograph induce measurable changes in diaphragm
      kinetics.

PMID- 9232306
TI  - Continuous oesophageal aortic blood flow echo-Doppler measurement during general
      anaesthesia in infants.
AB  - PURPOSE: Invasive haemodynamic monitoring during general anaesthesia in infants
      is usually limited to very high risk operations, such as cardiac surgery.
      Nevertheless, different surgical procedures and/or anaesthetic techniques justify
      additional monitoring for children, as for adults. The aim of this preliminary
      study was to evaluate the feasibility of using a new echo-Doppler device (Dynemo
      3000) capable of measuring continuous aortic blood flow during general
      anaesthesia in infants. METHODS: Aortic blood flow (ABF) was measured with a
      small oesophageal probe designed for newborns and infants. The aortic flowmeter
      was connected with satellite devices to visualise the haemodynamic profile which
      included ABF, pre-ejection period (PEPi), left ventricular ejection time (LVETi),
      mean arterial pressure, heart rate, stroke volume and systemic vascular
      resistance. Twelve infants, aged 8-26 mo, undergoing surgery under general
      anaesthesia were successively included in the evaluation of this device.
      Isoflurane (1% end-expired concentration) was introduced to maintain anaesthesia
      after induction with halothane, midazolam, fentanyl and atracurium. RESULTS:
      Correct positioning of the probe was easily obtained in all cases and the
      recording quality was excellent, whatever the operative position. Recordings of
      haemodynamic data showed some myocardial depression from isoflurane: decreased
      ABF (indexed to body surface area) and lengthened PEP/LVET (2.24 +/- 0.53 L.min
      1.m-2 and 0.32 +/- 0.05 respectively, before introduction of isoflurane and 1.71
      +/ 0.53 L.min-1.m-2 (P = 0.027) and 0.39 +/- 0.06 (P = 0.007) with isoflurane).
      CONCLUSION: These preliminary results suggest that this continuous ABF echo
      Doppler device may be valuable for peri anaesthetic monitoring in infants.

PMID- 9232307
TI  - Electrocardiographic "pacemaker pseudo-spikes" and radio frequency interference.
AB  - PURPOSE: To present a case of apparent interference of an ECG monitor by
      radiofrequency interference (RFI) and to provide a brief review of RFI issues to
      critical care medicine. CLINICAL FEATURES: A 74-yr-old woman, with an implanted
      pacemaker, underwent major spinal surgery. In the post-anaesthesia care unit, the
      cardiac monitor demonstrated graphic evidence of pacemaker malfunction but there
      was no apparent effect on the patient. Investigation by the hospital's biomedical
      personnel led to the conclusion that RFI was being interpreted by the monitor as
      abnormal pacemaker activity. CONCLUSION: With the emergence of portable, battery
      operated communication devices, there is an increased risk of RFI within
      hospitals. Antennas and repeaters are required to receive and boost the signal
      levels of these devices to improve signal quality. They are located throughout
      hospitals and may be situated near patient care areas. Patient monitors may
      receive these signals, misinterpret them as being patient-generated and output
      erroneous information. In the case described, the monitor was presented with RFI
      signals and interpreted as pacemaker spikes, generating a tracing suggestive of
      pacemaker malfunction. Troubleshooting strategies and minimizing the potential
      impacts of RFI on patient monitors are discussed.

PMID- 9232308
TI  - Metabolic events with spontaneous malignant hyperthermia crisis in an
      anaesthetized pig.
AB  - PURPOSE: To analyze metabolic changes associated with a fulminant malignant
      hyperthermia (MH) crisis developed spontaneously in an MH susceptible pig which
      was part of 12 pigs undergoing metabolic investigation (six MH susceptible and
      six controls) and had been anaesthetized with a non-triggering agent
      (pentobarbitone). METHODS: The pig was placed in a cradle and then inserted into
      a 4.7 T magnet bore. The semi-membranous muscle was submitted to three repetitive
      stimulation-recovery sessions. 31-P magnetic resonance spectra and mechanical
      data were recorded. RESULTS: The pig developed a non-rigid MH crisis during
      recovery from the second set of experiments. Although no mechanical work was
      performed, dramatic metabolic changes were noted. Twitch tension decreased
      progressively reaching zero while mouth temperature continuously increased to
      44.5 degrees C. Phosphocreatine (PCr) consumption was coupled to Pi accumulation.
      Also, a marked intracellular acidosis and a large accumulation of
      phosphomonoesters (PME) were observed, probably as a result of massive glycolysis
      activation. Interestingly, ATP level remained constant. CONCLUSION: These
      irreversible mechanisms may constitute a metabolic dead-end coupling calcium
      pumping ATP-consuming processes and ATP synthesis through PCr breakdown and
      anaerobic glycolysis. They do not differ from metabolic changes previously
      reported in rigid forms of MH crisis.

PMID- 9232309
TI  - Nocifensive reflex thresholds in rats: measures of central nervous system effects
      of barbiturates.
AB  - PURPOSE: To characterize the pharmacodynamic relationships between plasma
      pentobarbitone and thiopentone concentrations and nocifensive reflexes during
      emergence from anaesthesia. METHODS: Forty-nine rats were studied. Plasma
      barbiturate concentrations were measured with high performance liquid
      chromatography. Nocifensive reflexes were assessed with the hindlimb withdrawal
      latency (WL) to heat and the somatic motor response threshold (SMRT) to tail
      pressure. In Protocol I, SMRT, WL, sedation, and the presence of paw-licking and
      the righting reflex were assessed in unrestrained rats before and every 10 min
      for two hours after an intraperitoneal injection of pentobarbitone (30 mg.kg-1).
      Plasma pentobarbitone kinetics were determined in a separate group of rats. In
      Protocol II, SMRT and drug concentrations were measured concurrently in partially
      restrained animals before and for 35 min after a computer-controlled i.v. bolus
      of thiopentone. In Protocol III the SMRT-plasma thiopentone relationship was
      determined during increasing and decreasing plasma thiopentone concentrations.
      RESULTS: Enhancement of both nocifensive reflexes was observed in the
      unrestrained animals. Enhancement of SMRT was maximal [175% (153-197) of control
      values] at a mean plasma thiopentone concentration of 11 (9-13) micrograms.ml-1.
      The SMRT-plasma thiopentone curve showed a mean efflux-influx difference in
      plasma thiopentone concentration of 4(2.3-5.7) micrograms.ml-1. CONCLUSIONS:
      Barbiturate-associated nocifensive reflex enhancement occurs in unrestrained
      animals with both thermal and pressure stimuli. The SMRT-plasma thiopentone
      concentration relationship during emergence from anaesthesia was similar to that
      observed previously during induction. The thiopentone plasma concentration-SMRT
      plot showed an equilibrium delay similar to that previously described by others
      for thiopentone at an electroencephalographic effect site.

PMID- 9232310
TI  - Propofol inhibits medullary pressor mechanisms in cats.
AB  - PURPOSE: Propofol may cause hypotension and the mechanism is complex. The present
      study was designed to determine the direct actions of propofol in medulla of
      cats. METHODS: Mean systematic arterial pressure (MSAP), heart rate (HR) and
      cardiac contractility (dp/dt) were compared before and after administration of
      propofol the femoral vein (2, 3, or 4 mg.kg-1), vertebral artery (1 mg.kg-1) or
      the lateral cerebral ventricle (0.5 mg.kg-1) in eight anaesthetized cats. To
      study the direct effect of propofol in medulla, pressor areas of the dorsomedial
      medulla (DM) and rostral ventrolateral medulla (RVLM), or the depressor area of
      the caudal ventrolateral medulla (CVLM) were first identified with electrical
      stimuli and then confirmed by pressure microinjection of glutamate (Glu, 0.25M,
      30 nl) via a multibarrel-micropipette in 28 cats. One hour later, propofol
      (0.001%, 50 nl) was microinjected at the same site. Electrical stimulation and
      Glu were applied again to compare changes of SAP, HR and dp/dt with that of the
      control. RESULTS: Propofol dose-dependently decreased SAP, HR and cardiac
      contractility. The percent increase of MSAP induced by Glu were reduced by
      propofol in DM (59 +/- 3% vs 13 +/- 2%, n = 11, P < 0.01) or in RVLM (56 +/- 4%
      vs 18 +/- 2%, n = 9, P < 0.01). In CVLM, propofol slightly but not significantly
      increased depressor responses elicited by Glu (-27 +/- 2% vs -33 +/- 3%, n = 5, P
      > 0.05). CONCLUSION: Our results show that propofol principally inhibits the
      vasomotor mechanism in the dorsomedial and ventrolateral medulla to effect its
      hypotensive actions.

PMID- 9232311
TI  - Symposium on ergonomics in drug delivery.

PMID- 9232312
TI  - Rare complication after stellate ganglion block.

PMID- 9232313
TI  - The LMA for the application of postoperative CPAP.

PMID- 9232314
TI  - Airway anaesthesia during fibreoptic endoscopy.

PMID- 9232315
TI  - Paradoxical vocal cord motion.

PMID- 9232316
TI  - Incorrect analysis of data leads to incorrect conclusions.

PMID- 9232317
TI  - A simple method with no additional cost for monitoring ETCO2 using a standard
      nasal cannulae.

PMID- 9232318
TI  - Elimination of intercellular junctional communication requires lower Ras(leu61)
      levels than stimulation of anchorage-independent proliferation.
AB  - One of the effects of transformation by a variety of factors is a decrease in gap
      junctional, intercellular communication (GJIC). To investigate the role of the
      Ras oncogene product in gap junction closure, and to incorporate GJIC into the
      gamut of transformation-related properties which can be regulated by increasing
      levels of oncogene expression, a panel of murine C3H10T1/2 and 3T3L1 fibroblasts
      was constructed in which graded increments of Ras(leu61) could reliably be
      obtained. The inducibly activated Ras(leu61) protein substantially reduced or
      eliminated GJIC at levels much lower than those needed for neoplastic
      transformation, as indicated by acquisition of the ability to proliferate in the
      absence of anchorage. These results indicate that disruption of GJIC, although
      necessary, is not sufficient for neoplastic transformation in this system.

PMID- 9232319
TI  - Detection of membrane-associated human chorionic gonadotropin and its subunits on
      human cultured cancer cells of the nervous system.
AB  - Cultured human cancer cells from the nervous system, which included brain
      cancers, neuroblastomas, medulloblastomas, and retinoblastomas, were analyzed by
      analytical flow cytometry for the presence of membrane-associated human chorionic
      gonadotropin (hCG), its subunits, and fragments. Live cells and a panel of
      monoclonal antibodies directed to epitopes located in three different sites of
      the hCG molecule were used in the analysis. For in vivo studies, the cultured
      human glioma cells were grown in athymic (nude) mice, and their tumors were
      excised and fixed in Bouin's fixative, and embedded in paraffin for subsequent
      immunocytochemical analysis of tissue sections. Cells from a benign uterine
      leiomyoma were used as a negative control. Membrane-associated and cytoplasmic
      hCG, its subunits, and its fragments were present in cells from all the cancers
      studied. These results correlate with our in vitro and in vivo studies which
      showed the presence of translatable levels of hCG beta mRNA in all cancers,
      including the cancers of the nervous system, proving that these malignant
      neoplasms are no different from carcinomas, sarcomas, malignant lymphomas, or
      leukemias in that they all have the same biochemical denominator. Our findings
      give the scientific basis for the use of active and/or passive immunization
      against hCG for prevention or as a primary adjuvant therapy for these types of
      cancers.

PMID- 9232320
TI  - Investigation of Vicia graminea lectin- and Vicia unijuga lectin-binding
      glycoproteins as novel oncofetal antigens in cyst and ascitic fluids of human
      ovarian tumors in benign, dysplastic, and malignant stages.
AB  - Perchloric acid-soluble fractions (PASFs) were obtained from cyst fluids of human
      benign ovarian mucinous cystadenoma, benign dermoid cyst, "borderline" mucinous
      cystadenoma, and malignant ovarian clear cell carcinoma, and from fluids of
      malignant embryonal carcinoma and malignant serous cystadenocarcinoma. PASFs from
      benign lesions did not react with Arachis hypogaea lectin (PNA), Vicia graminea
      lectin (VGA), or Vicia unijuga lectin (VUA). PASFs from "borderline" lesions
      reacted with PNA but did not react with VGA and VUA. PASFs from malignant tumors
      reacted with PNA, VGA, and VUA. These PASFs did not react positively against anti
      M or -N sera. These results show that VGA- and VUA-binding glycoprotein (Vgu
      glycoprotein) exist in PASFs from malignant ovarian tumors, and that PNA-binding
      glycoprotein was present in PASFs from malignant and "borderline" ovarian tumors.
      Furthermore, we found the existence of Vgu glycoprotein in PASFs from various
      human cancer cell lines; however, the antigens were not found in PASFs from
      benign human cell lines.

PMID- 9232321
TI  - The enhancing effect of sodium nitrite on virus-induced leukemia in mice.
AB  - A study of the effect of sodium nitrite (SN) on leukemia development in mice
      induced by Rauscher Leukemia virus (RLV) (Balb/c mice), Mazurenko leukemia virus
      (MaLV) (CC57Br mice), and Gross leukemia virus (GLV) (AKR/J mice) was performed.
      SN was administered in water (at concentrations of 5.0, 50.0, 500.0, and 2000.0
      mg/l, by NaNO2). A moderate, yet statistically significant acceleration of
      leukemia development was observed in some groups of SN-treated mice. Our findings
      and the literature provide evidence that SN has the capacity to enhance the
      carcinogenic effect of leukemia viruses in vivo.

PMID- 9232322
TI  - DNA content and thymidine labeling index correlate with prognosis in squamous
      cell carcinoma of the larynx.
AB  - The prognostic value of proliferative activity was determined in 48 cases of
      squamous cell carcinoma of the larynx. Tumor samples were obtained during
      surgery: DNA content was determined by static cytometry with an image analysis
      program, and cell kinetics were analyzed by the in vitro thymidine labeling index
      (T-LI). The DNA content analysis visualized a diploid cellular population in 32
      cases and an aneuploid cellular population in 16 cases. The DNA content was not
      significantly related to the sex and the age of the patients or the TN stage of
      the tumors, but to histological grade (p = 0.03). Similarly significant
      correlation was found between T-LI and age of the patients, indeed the median
      value was higher in patients older than 59 (p = 0.024). T-LI was not related to
      the sex of the patients, or to the histological grade or the TN stage of the
      tumors. In multivariate analysis, using the Cox model, T-LI was the most
      important prognostic parameter (p = 0.015), superior to DNA content (p = 0.021)
      and to TN stage (p = 0.047; p = 0.043). From the data obtained in this study it
      can be concluded that evaluation of DNA content and thymidine labeling index in
      squamous cell carcinoma of the larynx may be new independent parameters of
      prognosis and may contribute to optimal and individualized therapy.

PMID- 9232323
TI  - Detection of p53 nuclear protein accumulation in brushings and biopsies of
      Barrett's esophagus.
AB  - Alterations in the tumor suppressor gene p53 may represent a useful prognostic
      marker of premalignant or malignant disease in Barrett's dysplasia or esophageal
      adenocarcinoma. Immunohistochemistry was used to establish the ability to detect
      nuclear accumulation of altered p53 protein in esophageal brushings as well as
      biopsies, and to examine for p53 alterations in a group of 18 patients with
      Barrett's esophagus enrolled in a surveillance and endoscopy program, p53 protein
      accumulation was easily detected in esophageal brushings, and the results
      correlated well with matched biopsies (9/11). In patients enrolled in
      surveillance endoscopy, 1 brushing of 22 was positive for p53 protein
      accumulation. In this patient, who received preoperative radiation and
      chemotherapy, the positive p53 result correlated with positive cytology for
      residual adenocarcinoma. All Barrett's esophagus brushings negative for p53
      protein were benign by cytologic, morphologic criteria. The immunohistochemical
      detection of p53 alterations in esophageal brushing and biopsy specimens may
      provide useful information in patients undergoing surveillance for esophageal
      dysplasia and adenocarcinoma.

PMID- 9232324
TI  - Cell-cycle arrest in G0/G1 phase of growth factor-induced endothelial cell
      proliferation by various calcium channel blockers.
AB  - Calcium channel blockers cause antiproliferative effects on various cells in
      culture. Since angioneogenesis is a crucial step in the development of tumor
      growth, we examined the influence of different calcium channel blockers on human
      umbilical arterial endothelial cell (HUAEC) growth. Cell growth was measured by
      cell count, by [3H]thymidine incorporation, and by a 5-bromo-2-deoxyuridine (BrdU
      incorporation immunofluorescence assay. Cell-cycle analysis was performed by flow
      cytometric analysis. Nifedipine, isradipine, diltiazem, and verapamil dose
      dependently inhibited the basic fibroblast growth factor (bFGF)-induced
      [3H]thymidine incorporation. Fifty micromolars of nifedipine, isradipine,
      diltiazem, and verapamil completely inhibited bFGF-induced proliferation of
      HUAEC. Ten micromolars of each calcium channel blocker abolished the bFGF-induced
      increase in cell count. Five micromolars of isradipine completely blocked the
      bFGF-induced BrdU incorporation. Stimulation of HUAEC with bFGF (50 ng/ml) for 24
      h caused a 2-fold increase in cells that entered S and G2+M phase in comparison
      with control cells. Five micromolars of isradipine abolished this effect
      completely. We conclude that calcium channel blockers are able to inhibit cell
      proliferation by a cell-cycle arrest in G0/G1 phase.

PMID- 9232325
TI  - Preventive effect of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with
      uracil on colonic carcinogenesis induced by 1,2-dimethylhydrazine in rats.
AB  - Thymidylate synthetase (TS) and thymidine kinase (TK) are key enzymes in de novo
      and salvage pathways for pyrimidine nucleotide synthesis, respectively. A high
      incidence of colorectal adenocarcinomas with varied grades of cell
      differentiation can be induced by 1,2-dimethylhydrazine (DMH) in rats. The marked
      increases of TS and TK activities were found in the poorly and well
      differentiated adenocarcinomas of the colon, respectively. Oral administration of
      1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) markedly
      reduced the number and accumulated area of colonic carcinomas, and TS activity in
      the poorly differentiated adenocarcinomas. A potential balance between the de
      novo and the salvage pathways for pyrimidine nucleotide synthesis was suggested
      to be related with the histopathological grades of cell differentiation.
      Suppression of colonic TS activity by UFT administration reduced the colonic
      carcinogenesis and the potency of the poorly differentiated adenocarcinomas of
      the colon.

PMID- 9232326
TI  - Analysis of specific accumulation of radiolabeled anti-carcinoembryonic antigen
      monoclonal antibody CEA 102 in colorectal cancer using computed radiography.
AB  - The specific accumulation of radiolabeled anti-carcinoembryonic antigen (CEA)
      monoclonal antibody (MoAb) CEA 102 in colorectal cancers was investigated by
      autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five
      patients with colorectal cancer were injected intravenously with [13I]-labeled
      intact CEA 102 or its F(ab')2. Primary tumor and liver metastases were
      successfully detected by external scanning with gamma camera in four cases.
      Autoradiographic study using FCR showed predominant localization of [13I]-labeled
      CEA 102 in primary tumors and liver metastases in all cases. Even the small-sized
      liver metastasis (0.5 cm) was clearly visualized. The pixel distribution curves
      showed the heterogeneity of the distribution of administered MoAb in the tumors.
      In the quantitative distribution analysis of CEA 102, the uptake of the primary
      tumor was 10-fold greater than that of the normal colon mucosa. These results
      suggest that MoAb has great potential in radioimmunodetection as well as possible
      use in antibody-directed therapy.

PMID- 9232327
TI  - Epidermal growth factor receptor in human hepatocellular carcinoma.
AB  - To determine whether a relationship exists between expression of epidermal growth
      factor receptor (EGFR) and clinicopathological characteristics of hepatocellular
      carcinoma (HCC), EGFR was examined in 25 patients surgically treated for HCC
      using [125I]1-labeled EGF binding assay. Six cases were classified as stage I, 12
      as stage II, 4 as stage III, and 3 as stage IV. Partial hepatectomy was performed
      in 11 cases, segmentectomy in 6, and lobectomy in 8. The level of EGFR in HCC was
      8.9 (14.6) fmol/mg protein in HCC and 11.4 (9.2) fmol/mg protein in the adjacent
      noncancerous diseased liver tissues, and EGFR level in HCC was significantly
      lower than that of noncancerous liver tissues. HCC stage I + II had significantly
      lower levels of EGFR compared with stage III + IV (p < 0.05). Our study showed no
      obvious correlation between EGFR levels and other pathologic characteristics,
      such as tumor diameter, Edmondson's grade, extracapsular invasion, and vascular
      invasion. There was no significant difference in EGFR level between DNA diploid
      and aneuploid tumors. These results suggest that EGFR is not a relevant oncogenic
      factor for HCC.

PMID- 9232328
TI  - The association of ethnicity and the incidence of mammary carcinoma in situ in
      women: 11,436 cases from the California Cancer Registry.
AB  - Ethnic differences in the incidence of mammary carcinoma in situ (CIS) in women,
      as well as differences in the percentages of carcinomas diagnosed in the in situ
      stage, have been calculated from the 11,436 cases of CIS in the California Cancer
      Registry (CCR) for the years 1988 through 1992. White women have an average
      annual age-adjusted incidence (AAAIR) of 17.4/100,000; black women, 11.4/100,000;
      Hispanic women, 7.6/100,000; and Asian/other women, 8.3/100,000. White women have
      11.8% of their carcinomas diagnosed in the in situ stage; black women, 10.2%;
      Hispanic women, 9.7%; and Asian/other women, 12.2%. In all ethnicities, CIS is
      predominantly a disease of postmenopausal women and is first diagnosed at an
      earlier age in nonwhite women. All of these observations have implications in the
      planning and evaluation of health care delivery and cancer control activities.
      Moreover, the younger age at diagnosis of women with CIS compared with those with
      invasive carcinoma supports the concept that CIS proceeds to invasive cancer.

PMID- 9232329
TI  - Providing information about breast cancer via public forums.
AB  - This study examines whether persons who attended a breast cancer education summit
      or received written materials (i) exhibited improved knowledge about breast
      cancer; and (ii) used the information themselves, share it with others, or
      implemented community education/screening programs. Participants (92 lay persons,
      67 health professionals who attended; 44 who did not attend but received written
      materials) were primarily female, with a mean age of 47. They completed a 10-item
      knowledge questionnaire on four occasions (pre-conference, immediately post
      conference, 9 weeks, 6 months). On the third and fourth occasion, participants
      also were asked how they had used the information. Paired samples t tests
      revealed that lay individuals (p < 0.001) and health professionals (p < 0.001)
      exhibited improved knowledge of breast cancer after attending the conference,
      used the information in their personal health care, and shared it with others,
      and some implemented education and screening programs. Of nonattendees, only the
      health professional group retained knowledge gain over time. A conference can
      produce increased knowledge about breast cancer and stimulate attendees to use
      information for themselves and share it with others. For lay persons, conference
      attendance is superior (p < 0.01) to written materials alone, in achieving long
      term gain in knowledge.

PMID- 9232331
TI  - A case of self-experimentation.

PMID- 9232330
TI  - Employee response to a company-sponsored program of colorectal and prostate
      cancer screening.
AB  - Studies done in the mid-1970s documented increased risk for respiratory cancer
      and leukemia among employees in a chemical company manufacturing plant where
      chloromethyl ethers were used in production from 1948 to 1971. In the late 1980s,
      the company informed current and former employees about the results of follow-up
      studies which showed a moderation of risk of respiratory cancer and leukemia. New
      data showing elevated rates of mortality from colorectal, prostate, bladder, and
      pancreatic cancer in the population were also reported. Via mailed
      correspondence, the company made a no-cost program of colorectal and prostate
      cancer screening available to employees upon request; and information about
      bladder and pancreatic cancer was made available. Thirteen percent of employees
      in the population indicated interest in colorectal and prostate cancer screening
      (response). Thirty-one percent of these responders were screened (adherence).
      Multivariate analyses showed that education and length of employment in the plant
      were positively associated with response. Being white was positively associated
      with response for younger workers; while among older workers being male was
      positively associated with response. In terms of adherence, we found that older,
      more highly educated workers were more likely to have a screening examination.
      Findings indicate that employee participation in workplace-sponsored colorectal
      and prostate cancer screening can vary according to worker sociodemographic
      factors and length of employment in areas of potential exposure.

PMID- 9232332
TI  - Cigarette smoking and large cell carcinoma of the lung.
AB  - Large cell carcinoma is the fourth most common histological type of lung cancer
      in the United States. Cigarette smoking causes large cell lung cancer, but it is
      uncertain whether the effect varies with the amount and duration of smoking. This
      uncertainty stems from ambiguity in the histopathological classification of large
      cell cancer, especially before 1971, and the relatively infrequent occurrence of
      large cell cancer in epidemiological studies. The present case-control
      investigation demonstrates that the risk of large cell cancer increases with both
      the frequency and number of years of cigarette smoking. The odds ratio associated
      with smoking two or more packs/day was 37.0 (95% confidence interval, 16.4-83.2)
      in men and 72.9 (35.4-150.2) in women. It is concluded that cigarette smoking is
      the predominant cause of large cell lung cancer.

PMID- 9232333
TI  - Body mass index and the risk of cancers of the gastric cardia and distal stomach
      in Shanghai, China.
AB  - The divergent incidence patterns of gastric cardia and distal stomach cancers
      suggest different etiologies. Although obesity has recently been linked to cardia
      cancer in Western populations, its association with distal stomach cancer remains
      unclear. This study examined the relation of anthropometric measurements to risk
      by subsites of stomach cancer in a Chinese population. We identified 1124
      population-based cases of stomach cancer, ages 20-69 years, newly diagnosed
      between December 1988 and November 1989 in Shanghai, China. Controls (n = 1451)
      were randomly selected from permanent Shanghai residents and frequency-matched to
      cases by age and sex. Information on demographic characteristics, height and
      weight, diet, smoking, and other exposures was obtained by trained interviewers
      in person. The body mass index (BMI) was calculated as weight in kilograms
      divided by height in square meters and categorized into quartiles based on the
      distribution among controls. Odds ratios and 95% confidence intervals were
      estimated using logistic regression models, simultaneously adjusting for age,
      education, income, cigarette smoking (men only), alcohol drinking (men only),
      intake of total calories, and chronic gastric diseases. For gastric cardia
      cancer, the odds ratios among men were 1.4, 1.5, and 3.0 in the second, third,
      and fourth quartiles of usual BMI (P for trend, < 0.01). Among women, elevated
      risks also were associated with excess weight, but the gradient in risk was not
      smooth. Risk patterns for usual body weight, maximum BMI, and minimum BMI were
      similar to those found for usual BMI. For distal stomach cancer, no association
      with usual BMI was observed among men, but a slightly elevated risk was seen
      among women. Our observations in China support recent findings in Western
      populations that obesity contributes to the risk of gastric cardia cancer,
      especially among men.

PMID- 9232334
TI  - Serum micronutrients and prostate cancer in Japanese Americans in Hawaii.
AB  - Numerous dietary studies and several serum micronutrient studies have produced
      equivocal results on the relation of vitamins A and E to prostate cancer risk. To
      evaluate this association further, we conducted a nested case-control study in a
      cohort of 6860 Japanese-American men examined from 1971 to 1975. At the time of
      examination, a single blood specimen was obtained, and the serum was frozen.
      After a surveillance period of more than 20 years, 142 tissue-confirmed incident
      cases of prostate cancer were identified. Their stored sera and those of 142
      matched controls were measured by high-performance liquid chromatography for the
      following: total carotenoids, lutein, zeaxanthin, beta-cryptoxanthin, lycopene,
      alpha-carotene, beta-carotene, total retinoids, retinol, total tocopherols, alpha
      tocopherol, delta-tocopherol, and gamma-tocopherol. Odds ratios for prostate
      cancer, based on quartiles of serum micronutrient levels, were determined using
      conditional logistic regression analysis. The odds ratio for the highest
      quartiles were 1.8 (95% confidence interval, 0.9-3.9) for beta-cryptoxanthin, 1.6
      (0.8-3.5) for beta-carotene, 0.8 (0.4-1.5) for retinol, and 0.7 (0.3-1.5) for
      gamma-tocopherol, but none of the differences was statistically significant. For
      the other micronutrients, the results were also unremarkable. The findings of
      this study indicate that none of the micronutrients is strongly associated with
      prostate cancer risk.

PMID- 9232335
TI  - Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians
      of Los Angeles, California, a low-risk population for NPC.
AB  - Mutatins of the p53 tumor suppressor gene are rare in nasopharyngeal carcinoma
      (NPC) patients who reside in high-risk areas, such as Southeastern China. Among
      this high-risk group, a pre-existing infection with the EBV and consumption of
      Cantonese salted fish are closely associated with NPC. We investigated the
      prevalence of p53 mutations in 28 primary NPC specimens from white (including
      Hispanic) and African-American patients in Los Angeles, who are at low risk for
      NPC. Using PCR-based single-strand conformational polymorphism and direct
      sequencing, we found four mutations (14%) in exons 5-8 of the p53 gene in four
      patients. All were C-to-T transition mutations: two were present in exon 5-one at
      codon 142 [CCT (Pro)-->CTT (Leu)] and another at codon 144 [CAG (Gln)-->TAG (stop
      codon)]. The other two mutations were identified in exon 8: one at codon 273 [CGT
      (Arg)-->CAT (His)], a CpG site, and one at codon 271, a silent mutation [GAG
      (Glu)-->GAA (Glu)]. This is the first report investigating the presence of p53
      missense mutations in NPC among a low-risk population. Our data indicate that p53
      is also an infrequent event among NPC patients at low risk for the disease.

PMID- 9232336
TI  - p53 mutations in head and neck cancer: new data and evaluation of mutational
      spectra.
AB  - It has been suggested that the frequency, type, and location of p53 mutations
      (mutational spectra) can be linked to specific exogenous and endogenous
      carcinogenic agents and processes. Squamous cell carcinoma of the head and neck
      (SCCHN) provides an excellent tumor model to evaluate the utility of the p53
      mutational spectra, given that it has well-defined and strong risk factors
      (tobacco and alcohol). The purpose of this analysis was to establish the pattern
      of p53 mutations in SCCHN and evaluate this mutational spectrum in comparison to
      the spectra for other cancers with similar and different risk factors, including
      cancers of the esophagus, lung, and colon. p53 mutational data were obtained from
      head and neck tumors collected at the University of North Carolina Hospitals and
      the published literature. A total of 14 of 33 tumors from the University of North
      Carolina Hospitals (42%) were found to have a p53 mutation. The alterations
      included three transversions, seven transitions, two deletions, and two suspected
      codon 47 polymorphisms. In general, SCCHN and esophageal cancer share a similar
      mutational pattern in contrast to colon cancer. These two aerodigestive tract
      cancers were statistically different from lung cancer, despite sharing tobacco as
      a major risk factor. For example, G-->T transversions, a mutation type considered
      to be characteristic of exogenous DNA-damaging agents including tobacco smoke
      carcinogens, varied among tobacco-related cancer sites (14% SCCHN, 11%
      esophageal, and 31% lung) in contrast to colon cancer (6%). The comparison of
      mutational spectra for SCCHN and other cancers indicates that the effects of both
      tobacco and alcohol exposure may yield a pattern of p53 mutations that reflects
      elements of both exogenous and endogenous exposures.

PMID- 9232337
TI  - Urinary estrogen metabolites and breast cancer: a case-control study.
AB  - Preliminary studies suggest that the estrogen metabolite 16 alpha-hydroxyestrone
      is associated with breast cancer, whereas 2-hydroxyestrone is not. However,
      epidemiological studies evaluating this relationship and taking established risk
      factors for breast cancer into account are lacking. The purpose of this study was
      to examine the association of the ratio of the urinary estrogen metabolites (2
      hydroxyestrone and 16 alpha-hydroxyestrone) and of the individual metabolites
      with breast cancer. A spot urine sample, a brief history, and clinical data were
      collected from breast cancer cases (n = 42) and from women coming to the hospital
      for a routine mammogram or attending a free breast cancer screening (n = 64). 2
      Hydroxyestrone and 16 alpha-hydroxyestrone were measured by enzyme immunoassay,
      and the estrogen metabolite ratio (EMR; 2-hydroxyestrone:16 alpha-hydroxyestrone)
      was computed. Cases and controls were similar in terms of age (mean age of cases,
      53.8 +/- 15.1 years, versus 54.2 +/- 10.4 years for controls; P = 0.9) and
      demographics. Mean EMR was not associated with breast cancer overall (1.67 +/-
      0.80 versus 1.72 +/- 0.66; P = 0.7). However, in postmenopausal women, the mean
      EMR was significantly lower in cases compared to controls (1.41 +/- 0.73 versus
      1.81 +/- 0.71; P = 0.05). The multivariate adjusted odds ratios for the
      intermediate and lowest tertiles of the EMR relative to the highest among
      postmenopausal women were 9.73 (95% confidence interval, 1.27-74.84) and 32.74
      (95% confidence interval, 3.36-319.09), respectively. The test for trend was
      highly significant (P = 0.003). Analyses of the individual metabolites indicated
      that 16 alpha-hydroxyestrone was a strong risk factor. The EMR did not show any
      consistent associations with age, race/ethnicity, age at first birth, parity,
      body mass index, family history of breast cancer, smoking, or alcohol intake.
      These data suggest a strong, inverse association of the EMR and a strong positive
      association of 16 alpha-hydroxyestrone with breast cancer in postmenopausal
      women. Larger studies are needed to confirm these results and to assess the
      relationship of the EMR and of the individual metabolites with breast cancer,
      with attention to menopausal status and clinical factors and with adjustment for
      known breast cancer risk factors.

PMID- 9232338
TI  - Glutathione S-transferase class mu deletion polymorphism and breast cancer:
      results from prevalent versus incident cases.
AB  - A common deletion polymorphism in the gene coding for the glutathione S
      transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify
      carcinogenic epoxide intermediates and has been associated with increased breast
      cancer risk in some small studies. We studied the GSTM1 gene deletion
      polymorphism (conferring the null genotype) in 243 women who had prevalent breast
      cancer and 245 women without breast cancer, who were among the 32,826 women in
      the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent
      case series, the null genotype was slightly more common among cases (58%) than
      among controls (51%; age-adjusted odds ratio = 1.30; 95% confidence interval,
      0.91-1.86). Among cases, the prevalence of the GSTM1 deletion increased with
      duration of survival [68% for > or = 8 years since diagnosis; 57% for 4-8 years;
      51% for < 4 years; P (trend) = 0.04]. In an incident case series of 240 women who
      were diagnosed with breast cancer following blood collection and prior to June of
      1992 and compared with age-matched controls, the GSTM1 deletion was not
      associated with an elevation in risk (relative risk, 1.08; 95% confidence
      interval, 0.74-1.57). No significant interaction with cigarette smoking was
      evident. Thus, there was no significant increase in risk of incident breast
      cancer associated with the GSTM1 null genotype; however, the gene deletion
      polymorphism appeared to confer improved survival. These data suggest that odds
      ratios based upon prevalent cases in molecular epidemiologic studies may be
      biased due to differential survival. Further studies are required to determine
      whether this polymorphism is associated with improved breast cancer prognosis.

PMID- 9232339
TI  - Effects of indole-3-carbinol on the metabolism of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone in smokers.
AB  - Indole-3-carbinol (I3C) is a component of the human diet, occurring as a
      conjugate in certain cruciferous vegetables. I3C protects against carcinogenesis
      in a variety of animal models by modifying carcinogen metabolism. In mice, I3C
      decreases lung tumor formation by the tobacco-specific nitrosamine 4-(methyl
      nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by enhancing its hepatic clearance
      (M. A. Morse et al., Cancer Res., 50: 2613-2617, 1990). In this study, our goal
      was to determine whether I3C would have similar effects on NNK metabolism in
      smokers as it did in mice. Thirteen women took 400 mg of I3C on 5 consecutive
      days and maintained constant smoking habits during this period. Their urine was
      analyzed before and after the I3C treatment period for two metabolites of NNK: 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL
      Gluc). I3C treatment resulted in decreased levels of urinary NNAL, NNAL-Gluc, and
      NNAL plus NNAL-Gluc, and increased NNAL-Gluc:NNAL ratio in 10 of the 13 women.
      The mean decreases in NNAL (-0.27 +/- 0.09 pmol/mg creatinine, -23.4%) and NNAL
      plus NNAL-Gluc (-0.43 +/- 0.16 pmol/mg creatinine, -10.9%) were statistically
      significant as was the increase in NNAL-Gluc:NNAL ratio (1.1 +/- 0.5, 39.9%).
      These changes in urinary metabolites of NNK were consistent with those seen in
      mice treated with I3C and NNK; they suggest that I3C increased hepatic metabolism
      of NNK in our smokers. This is the first study to examine the effects of I3C on
      metabolism of an exogenous carcinogen in humans.

PMID- 9232340
TI  - Use of an improved method for analysis of urinary aflatoxin M1 in a survey of
      mainland China and Taiwan.
AB  - An improved monoclonal antibody immunoaffinity chromatography/high-pressure
      liquid chromatography/ fluorescence detection method was developed to measure
      aflatoxin (AF) exposure by quantifying AFM1 in human and rat urine samples.
      Analysis of different amounts of various AF metabolites showed that the
      immunoaffinity resin was highly selective for aflatoxin B1 (AFB1), AFB2, and
      AFM1. Recovery of added AFs increased with the amount of immunoaffinity resin and
      was virtually complete within the range of 0.01-10 ng of AFM1 by using 7 ml of
      resin. The detection limit of this method is 0.5 pg/ml urine. Rats dosed with
      tritiated AFB1 excreted in their urine tritiated AFM1, among other AF
      metabolites, as indicated by chemical derivative confirmation and
      cochromatography with authentic AFM1 and agreement of radioactivity and
      fluorescence quantitation. A linear dose-response relationship was found over the
      range of 0.05-50 micrograms/kg of body weight/day. Two humans dosed with 1.0
      microgram of pure AFB1 excreted 6-7% of the dose as urinary AFM1 over 5-7 days.
      Pooled urine samples from 30 men from each of 69 rural counties in mainland China
      and 16 survey areas in Taiwan, with two villages per county or area, were
      analyzed with this improved method (170 villages total). The correlation
      coefficient of urinary excretion of AFM1 compared between villages within all 85
      survey areas was 0.50 (P < 0.001). Sixty-five % of the samples contained
      detectable concentrations of AFM1 with an average excretion of 3.1 ng/12 h.
      Assuming an excretion rate of 2-6%, this AFM1 excretion corresponds to a very low
      average daily AF consumption of 0.1-0.3 microgram/day (possible range, 0-11
      micrograms/day). Patterns of urinary excretion of AFM1 were similar in mainland
      China and Taiwan.

PMID- 9232341
TI  - S phase determination in intact colonic crypts by histone H3 messenger RNA in
      situ hybridization and confocal microscopy.
AB  - Proliferating cells have a restricted three-dimensional spatial distribution
      within the crypt, which is the proliferative unit of the colon. Accurate
      quantitative and spatial analyses of S phase cells in the colon have therefore
      been limited by histological techniques. To overcome these limitations, S phase
      cells in microdissected intact colonic crypts of control, modified-starved, and
      refed rats were labeled by histone H3 in situ hybridization and analyzed by
      confocal microscopy. High-resolution digital images of the crypt cell nuclei
      stained with cyanine nucleic acid and of the labeled S phase cells were produced
      from confocal microscopic optical crypt sections. The S phase labeling index (LI)
      per whole crypt significantly (P < 0.001) discriminated the proliferative
      differences between control, modified-starved, and refed rats and correlated (r =
      0.92) with the LI determined from histological crypt sections of the same rats.
      The variance component of the LI attributable to differences between whole
      crypts, 0.44 (95% confidence interval, 0.38-0.51), was considerably smaller than
      that attributable to differences between histological crypt sections, 6.07 (95%
      confidence interval, 5.18-6.96). Confocal microscopy and histone H3 in situ
      hybridization of intact three-dimensional crypts enables precise in vitro
      quantitation and spatial analysis of the total and S phase crypt cells.

PMID- 9232343
TI  - Decrease of ornithine decarboxylase activity in premalignant gastric mucosa and
      regression of small intestinal metaplasia in patients supplemented with high
      doses of vitamin E.
AB  - The effect of high doses of vitamin E (Vit.E; 400 units/ day) on ornithine
      decarboxylase (ODC) activity and regression of small intestinal metaplasia (SIM)
      was studied in a 1-year double-blind intervention trial. Biochemical and
      morphological parameters were estimated in 14 evaluable SIM patients of 18 in the
      Vit.E group and in 16 of 18 intestinal metaplasia patients enrolled in control
      group (placebo). In the control group, there were no statistically significant
      changes in Vit.E content in blood plasma, ODC activity, and the rate of SIM in
      multiple biopsies from antrum gastric mucosa. In the Vit.E group, after 6 and 12
      months of intervention, the initial content of Vit.E in blood plasma increased
      from 6.4 +/- 0.9 up to 17.0 +/- 1.8 and 21.2 +/- 2.3 micrograms/ml, respectively,
      and the initial abnormally high activity of ODC, 62.6 +/- 7.8 units, decreased by
      53 and 65%, respectively. Histological analysis of multiple biopsies, taken from
      the gastric antrum of patients supplemented with Vit.E, revealed that in 8 of 14
      patients (57%) after 6 months and in 10 of 14 patients (71%) after 12 months, no
      signs of SIM were observed; gastroscopic dye procedure confirmed the regression
      of SIM in these cases and showed the presence of only small isolated stained
      areas identified as SIM.

PMID- 9232342
TI  - A clinical trial to evaluate the effect of vitamin C supplementation on in vitro
      mutagen sensitivity. The University of Texas M. D. Anderson Clinical Community
      Oncology Program Network.
AB  - Mutagen sensitivity, as measured by an in vitro assay, has been described as a
      risk factor for the development of several tobacco-related epithelial cancers. In
      vitro studies have indicated that sensitivity to the clastogenic effects of
      bleomycin on chromosomes was reduced with the introduction of ascorbic acid in a
      dose-dependent relationship. We report the results of a randomized clinical trial
      to determine whether increasing levels of oral ascorbic acid could reduce the
      levels of mutagen sensitivity. For this study, we recruited 228 healthy smokers
      from 21 centers around the country through the Clinical Community Oncology
      Program. Each individual was randomly assigned to one of four daily regimens:
      placebo, 1 g of ascorbic acid, 2 g of ascorbic acid, or 4 g of ascorbic acid.
      Treatments were administered for 16 weeks. Assessment of mutagen sensitivity was
      made at baseline and at weeks 4, 16, and 20 (4 weeks after cessation of
      treatment). Serum ascorbic acid levels were measured at baseline and at weeks 4
      and 16. Demographic and risk factor data were collected at baseline and at each
      measurement point. Analyses measured the differences of mutagen sensitivity
      levels across the four treatment arms, as well as investigating the correlation
      between serum ascorbic acid level and mutagen sensitivity levels in individuals.
      We did not find a dose-response relationship between ascorbic acid intake and
      mutagen sensitivity. Additionally, we did not find an association between serum
      ascorbic acid levels and mutagen sensitivity.

PMID- 9232344
TI  - DNA ploidy pattern and tumor suppressor gene p53 expression in gallbladder
      carcinoma.
AB  - The relationship between p53 gene expression and DNA content in advanced
      gallbladder carcinoma was studied. Fifty-three cases of advanced gallbladder
      carcinoma (45 primary tumors and 8 metastases) were analyzed, p53 protein
      expression was determined by immunohistochemistry, DNA content was measured by
      cytophotometric techniques. Study subjects included 45 (85%) female and 8 male
      patients, with an overall mean age of 58.6 years. Positive staining for p53
      protein was observed in 27 (51%) cases. In subserosal tumors, the expression was
      significantly less than that in tumors that reached the serosa (P = 0.01). Twenty
      nine (55%) cases were diploid and 24 were aneuploid. Sixty-seven % of primary
      tumors were diploid, whereas 87% of metastases showed an aneuploid DNA content.
      Both diploid and aneuploid tumors were positive for the p53 protein in the same
      proportion, and p53 was also expressed equally in both primary and secondary
      tumors. In advanced gallbladder carcinoma, the expression of the p53 gene was
      earlier than the accumulation of abnormal quantities of chromosomal DNA in the
      tumor cells. The determination of these events as markers in preneoplastic
      lesions is warranted in gallbladder carcinogenesis.

PMID- 9232345
TI  - Comparison of two enzyme-linked immunosorbent assay tests for diagnosis of
      Helicobacter pylori infection in China.
AB  - An ELISA based on a pool of United States strains of Helicobacter pylori was
      compared with a newly developed ELISA based on a pool of Chinese strains. Both
      assays were tested using sera from 132 Chinese study subjects with biopsy-proven
      H. pylori infection. Using cutpoints designed to yield equal specificities of
      94.9% in an uninfected control population, the sensitivity of the Chinese assay
      was 100.0%, compared to 97.7% for the United States assay (P = 0.25 by McNemar
      test). These results suggest that a H. pylori assay based on pooled antigens from
      United States strains will perform as well in the rural Chinese population as one
      based on antigens from Chinese strains.

PMID- 9232346
TI  - High [Ca2+]i domains, secretory granules and exocytosis.

PMID- 9232347
TI  - Distribution of Ca2+ extrusion sites on the mouse pancreatic acinar cell surface.
AB  - The localizations of Ca2+ extrusion sites in mouse pancreatic acinar cells during
      elevation of the intracellular free calcium concentration ([Ca2+]i) have been
      studied. During an agonist stimulated calcium elevation as well as when
      intracellular calcium is released from a 'caged compound', Ca2+ is primarily
      extruded from the apical secretory pole of the cells in spite of different
      spatial patterns of [Ca2+]i different sources of Ca2+, and the presence or
      absence of agonist. This is most likely due to a relatively high density of
      calcium pumps in the secretory granule region, although it could be explained by
      calcium pumps in this part of the cell having different characteristics from
      those in the basal membrane. The intensity of Ca2+ extrusion in the apical
      secretory pole is such that substantial (several millimoles per litre) changes of
      the free calcium concentration in the lumen of the acinus can occur during
      agonist stimulation.

PMID- 9232348
TI  - Effects of 1-methyladenine on nuclear Ca2+ transients and meiosis resumption in
      starfish oocytes are mimicked by the nuclear injection of inositol 1,4,5
      trisphosphate and cADP-ribose.
AB  - The treatment of prophase-arrested starfish oocytes with the hormone 1
      methyladenine (1-MA) induces the elevation of Ca2+ in both the cytoplasm and the
      germinal vesicle (nucleus), and is followed by the resumption of meiosis. The
      injection of the modulators of the intracellular Ca2+ channels inositol 1,4,5
      trisphosphate (InsP3) or cyclic adenosine diphosphate ribose (cADPr) into the
      germinal vesicle promoted meiosis resumption in the absence of 1-MA in about 50%
      of the oocytes. Caged InsP3 or caged cADPr were injected into the nuclei of
      oocytes together with the Ca2+ indicator calcium green dextran; their
      photoreleasing elicited nuclear calcium spikes which, in the case of cADPr, had
      repetitive behaviour. The spikes were abolished by the nuclear injection of
      antagonists or antibodies to the InsP3 or cADPr-sensitive Ca2+ channels. cADPr
      modulated channels were localized on the membranes of the nuclear envelope using
      specific antibodies conjugated with IgG-gold complexes.

PMID- 9232350
TI  - Characterization of the maitotoxin-induced calcium influx pathway from human skin
      fibroblasts.
AB  - Maitotoxin (MTX), a water-soluble polyether obtained from the marine
      dinoflagellate Gambierdiscus toxicus increased intracellular calcium in a
      concentration-dependent manner in fibroblasts obtained from human skin. The
      effect of this toxin was both saturable and of high affinity, showing an apparent
      half activation constant of 450 fM. The toxin did not release intracellular
      calcium storage compartments nor did the release of these compartments with
      thapsigargin or ionomycin affect the toxin response. The toxin effect was reduced
      significantly by pre-incubating the cells with 0.1% trypsin for 30 min, strongly
      suggesting that the toxin receptor is a plasmalemmal protein. The effect of MTX
      was partially inhibited by diphenoxylate.

PMID- 9232349
TI  - Receptor-dependent G protein-mediated Ca2+ sensitization in canine airway smooth
      muscle.
AB  - To determine the mechanisms of receptor-dependent Ca2+ sensitization in airway
      smooth muscle, canine tracheal smooth muscle (CTSM) was permeabilized with alpha
      toxin or beta-escin. Although the effects of 5-hydroxytryptamine (100 microM),
      histamine (100 microM), and the thromboxane A2 analogue U-46619 (100 microM) were
      negligible, carbachol (100 microM) and endothelin-1 (ET-1, 1 microM) evoked
      additional contractions of 47.0 +/- 5.90% and 25.0 +/- 5.37% (n = 6) at pCa 6.7
      with GTP (3 microM) (normalized to the maximum contraction at pCa 4.5) in alpha
      toxin-permeabilized CTSM. GDP-beta-S (1 mM) reversed the carbachol and ET-1
      responses completely. GTP-gamma-S (30 microM) and 4 beta-phorbol 12,13-dibutyrate
      (PDBu, 3 microM) increased the Ca2+ sensitivity (median effective pCa) of
      contraction by 1.8- and 4.4-fold, respectively (n = 4-11, P < 0.05). The effects
      of saturating concentrations of GTP-gamma-S and PDBu were additive. A synthetic
      peptide (T2) corresponding to the actin-binding site of calponin caused a dose
      dependent contraction of beta-escin permeabilized CTSM, with the peak effect (25
      +/- 4%, n = 4) at 1200 microM, PDBu (3 microM) caused contraction of the T2
      peptide-treated CTSM. In conclusion, Ca2+ sensitization of CTSM depends on
      receptor type and is mediated by G proteins and protein kinase C whose effects
      are additive, with a partial contribution by calponin.

PMID- 9232351
TI  - Novel variants of voltage-operated calcium channel alpha 1-subunit transcripts in
      a rat liver-derived cell line: deletion in the IVS4 voltage sensing region.
AB  - Using reverse transcriptase-PCR and Northern analysis, we have shown that the
      H4IIE cell line, derived from the Reuber H35 rat hepatoma, contains significant
      amounts of transcripts for the CaCh3 (neuroendocrine) and CaCh1 (skeletal muscle)
      L-type voltage-operated calcium channel alpha 1-subunits. Two of the CaCh3
      transcripts have a 45 bp deletion in the IVS4 membrane-spanning region which is
      the result of a mutation in genomic DNA. The deduced amino acid sequences of the
      PCR-derived clones of CaCh3 indicate that the mutation causes the loss of 15
      amino acids from the IVS4 region, including three of the six positively charged
      residues, which are thought to be part of the voltage-sensing mechanism of
      voltage-operated Ca2+ channels. Quantitative-PCR and Northern analysis indicate
      that one of the novel CaCh3 transcripts is present in sufficient amounts to imply
      it could play a functional role in Ca2+ inflow. RT-PCR analysis of hepatocytes
      isolated from rat liver detected transcripts of CaCh3 (without the IVS4 mutation)
      and CaCh2, but at considerably lower levels than observed for the isoforms in the
      H4IIE cell line. Transcripts of CaCh1 and CaCh2 were also detected at low levels
      in Jurkat T lymphocytes. Fluorimetric studies with the Ca(2+)-sensitive probe,
      Fluo-3, have shown that H4IIE cells exhibit receptor-activated and store
      activated (thapsigarin-induced), but not depolarisation (extracellular KCl)
      induced Ca2+ inflow. The mutant transcripts are unlikely to produce Ca2+ channels
      that are opened by membrane depolarisation. The idea that they may be opened by
      other mechanisms is briefly discussed.

PMID- 9232352
TI  - Kinetic and pharmacological properties of the calcium-activated chloride-current
      in macrovascular endothelial cells.
AB  - We have studied the kinetic and pharmacological properties of the Ca(2+)
      activated Cl- current (ICl,Ca) in cultured cell pulmonary artery endothelial
      (CPAE) cells by means of combined patch clamp and Fura-2 micro fluorescence
      measurements. The current was activated by loading the cells via the patch
      pipettes with Ca(2+)-buffered solutions. Currents activated slowly at positive
      potentials, and decayed rapidly at negative potentials. The time constant of
      activation decreased at more positive membrane potentials and more elevated
      intracellular Ca2+ concentrations ([Ca2+]i). The time constant of deactivation
      was Ca(2+)-independent and decreased at more negative potentials. Steady-state
      currents showed strong outward rectification, but the instantaneous current
      voltage relationship was almost ohmic. The calmodulin antagonists trifluoperazine
      (TFP) and calmidazolium inhibit ICl,Ca. Half maximal block for TFP occurred at
      5.7 +/- 2.1 microM (n = 16). GTP gamma S did not activate ICl,Ca, but activated a
      Cl- current similar to the volume-activated Cl- current (ICl,vol). [Ca2+]i for
      half maximal activation of ICl,Ca was voltage-dependent, and suggests that the
      apparent binding constant for Ca2+ decreases with depolarization. Its value at 0
      mV is 430 nM, and the binding site is 12% within the electrical field from the
      cytoplasmic side. The Hill-coefficient, nH, of the binding was larger than 1 and
      increased with depolarization. The maximal Cl- conductance at saturating [Ca2+]i
      did not depend on the membrane potential. RT-PCR experiments did not provide any
      evidence that the endothelial Ca(2+)-activated Cl- channel might be identical
      with a recently cloned Ca(2+)-sensitive Cl- channel (CaCC).

PMID- 9232353
TI  - cAMP-induced changes in the cytosolic free Ca2+ concentration in Dictyostelium
      discoideum are light sensitive.
AB  - The cytosolic free calcium concentration ([Ca2+]i) of the social amoeba
      Dictyostelium discoideum was analyzed after challenge with the chemoattractant
      cAMP. [Ca2+]i was measured by digital imaging in single cells loaded with the
      Ca2+ indicator Fura-2-dextran. Global stimulation with low concentrations of cAMP
      (0.1-1 microM) led to a global transient [Ca2+]i increase. This increase was
      abolished when cells were illuminated with high doses of light. However, after a
      short recovery period of several minutes, the cells again displayed the normal
      response. Inhibition of the [Ca2+]i elevation depended on the wavelength of
      illumination light. We compared the required recovery period of cells irradiated
      with either 340, 380, 405, 450 or 490 nm at defined intensities. Light of 405 nm
      had a pronounced effect; 340 nm alone or in combination with 380 nm was also
      effective, but to a lesser extent, whereas neither 450 nm nor 490 nm inhibited
      the [Ca2+]i increase, even at very high irradiance. The wavelength dependence
      matched the absorption spectrum of amoebae grown in darkness that contain a
      photopigment which seems to be responsible for phototaxis of single cells. Cells
      grown in darkness exhibited an increased sensitivity of the cAMP-induced [Ca2+]i
      transient towards light compared to light-grown cells. From these data we
      conclude that phototactic signaling could interfere with chemotactic signaling at
      the level of [Ca2+]i changes.

PMID- 9232354
TI  - Postprandial hypotension in Alzheimer's disease.
AB  - The degree of postprandial hypotension in patients with Alzheimer's disease (AD)
      is not known. We therefore studied ten AD patients and 23 controls before and
      after a meal. Seven AD patients but only six controls showed a fall in blood
      pressure (BP) of 20 mmHg or more. Maximum BP fall in AD patients was observed
      between 20 and 120 min after food ingestion. This differed from the time course
      in other groups with primary chronic autonomic failure. Postural hypotension
      occurred in two controls, but not in AD patients. Abnormalities in cardiac
      vasomotor regulation, gut peptide liberation or both could be responsible for
      postprandial hypotension in AD.

PMID- 9232355
TI  - Cardiovascular autonomic dysfunction in sickle cell anemia: a possible risk
      factor for sudden death?
AB  - Cardiovascular autonomic function tests were performed in 24 patients with sickle
      cell anemia (SCA). Twenty-five healthy Afro-Caribbean black subjects and 38
      healthy white subjects of Hispanic origin served as controls. Measurements based
      on heart rate variability (HRV) included the coefficient of variation (the
      standard deviation of the distribution of R-R intervals divided by the mean) and
      spectral analysis (low- and high-frequency bands) at rest, HRV during deep
      breathing (expiration-inspiration difference), Valsalva maneuver (Valsalva ratio)
      and lying-to-standing test (30:15 ratio). Fourteen patients (58.3%) were found to
      have cardiovascular autonomic dysfunction based on abnormal values for at least
      two cardiovascular autonomic function tests, whereas ten (41.7%) had preserved
      cardiovascular autonomic function. In contrast, all control subjects had normal
      cardiac autonomic function. SCA is known to be associated with sudden death.
      Involvement of autonomic nervous dysfunction in sudden death has been reported in
      various diseases and we suggest that this may be the case in SCA.

PMID- 9232356
TI  - Vagal control of heart rate variability in vasovagal syncope: studies based on 24
      h electrocardiogram recordings.
AB  - The autonomic nervous system has an important role in the pathophysiology of
      vasovagal syncope. The purpose of this investigation was to evaluate to what
      extent the autonomic system is involved in the mechanism of fainting and to
      characterize the profile of heart rate variability of individuals who are prone
      to undergo a critical event. Thirty patients (mean age 41 years) with vasovagal
      syncope and 15 comparable controls were monitored by 24-h electrocardiography.
      Heart rate variability was analysed over the whole 24 h and during the daytime
      and night-time using time domain parameters (average of heart periods, RR;
      standard deviation of heart periods, SDNN; standard deviation of the average of
      RR intervals over all the 5-min segments of the entire recording, SDANN;
      percentage of the total number of all RR intervals of pairs of adjacent RR
      intervals differing more than 50 ms over the entire recording, pNN50; the square
      root of the sum of the square of differences between adjacent RR intervals,
      rMSSD), as indicated by the Task Force for Clinical Use of Standard Measurements
      of Heart Rate Variability. These parameters explore the influence of the
      autonomic nervous system on sinus node function and provide information about the
      vagal control to the heart. Among these parameters, pNN50 and rMSSD were
      significantly reduced in individuals with vasovagal syncope when compared with
      controls, over each time period considered. The two parameters are related to
      high-frequency oscillations in the frequency domain and to the vagal influence of
      the heart. These results indicate that the vagal tone to the heart is altered in
      subjects who suffer from vasovagal syncope. The results of this study provide an
      insight into the pathophysiological mechanism of fainting and may offer another
      means of evaluating patients with syncope.

PMID- 9232357
TI  - Determinants of heart rate variability during deep breathing: basic findings and
      clinical applications.
AB  - The measurement of heart rate variation during forced breathing (HRDB) is a well
      known clinical test of parasympathetic function. It is known that normal values
      of HRDB are strongly dependent on age. However, little is known about other
      physiological factors that may lead to reduced HRDB values that may mimic
      parasympathetic failure. Thirty-two normal subjects (age 56.7 +/- 12.4 years) and
      32 neurological patients with pathological autonomic test findings (age 57.9 +/-
      10.2) were studied. Oscillations in heart rate and in mean arterial blood
      pressure were recorded in the supine position during forced breathing (6
      cycles/min) using the Finapres monitor. Amplitudes of heart rate and blood
      pressure waves at 6 cycles/min (HR6 and ABP6) as well as gain values (Gain6 =
      HR6/ABP6) and phase differences (delta phi 6) between HR and ABP waves were
      calculated by means of spectral analysis. The mean (+/-SD) HR6 in normal subjects
      was 6.34 +/- 3.36 cycles/min with a mean ABP6 of 5.11 +/- 2.49 mmHg. HR6
      correlated significantly with age (r = -0.426) and with ABP6 (r = 0.602). No
      significant correlation was found between HR6 and mean blood pressure, mean heart
      rate or sex. From 24 patients with pathological findings in the classical HRDB
      value, only nine could be classified as pathological when the effect of ABP6 was
      considered. In conclusion, ABP variations significantly influence the amplitude
      of heart rate variations during forced breathing. We interpret these findings in
      terms of a baroreflex mechanism of HRDB including both vagal and sympathetic
      efferents. Normal reference value tables for clinical HRDB studies should not
      only consider age but also the amplitude of blood pressure variations.

PMID- 9232358
TI  - Cardiovascular and hormonal responses to food ingestion in humans with spinal
      cord transection.
AB  - In sympathetic denervation due to primary autonomic failure, ingestion of food
      causes a fall in blood pressure (BP) and exacerbates postural hypotension. It is
      not known whether these responses occur in tetraplegics with physiologically
      complete cervical spinal cord transection, who also have sympathetic dysfunction
      because of disruption of descending spinal sympathetic pathways. We, therefore,
      studied the effect of a liquid meal on BP, heart rate (HR) and neurohormonal
      levels in tetraplegics. Paraplegics with low lesions and without sympathetic
      dysfunction served as controls. After food ingestion, there was no fall in BP in
      tetraplegics or in controls. HR did not change in either group. After fund,
      plasma noradrenaline was unchanged in tetraplegics, but rose in controls, while
      plasma renin activity (PRA) rose in tetraplegics but not in controls. The fall in
      BP and rise in HR on head-up tilt after the meal in tetraplegics was similar to
      that before the meal. There was no change in PRA following pre-prandial tilt in
      either group; post-prandial tilt raised levels in the tetraplegics, unlike in
      controls. Thus there is considerable variance in the responses to food between
      tetraplegics and paraplegic controls, and even greater differences when compared
      with published data in other autonomic disorders with sympathetic dysfunction;
      this may relate to the site and the nature of the sympathetic lesion and the
      ability to activate compensatory mechanisms.

PMID- 9232359
TI  - Effect of postural changes on arterial baroreflex sensitivity assessed by the
      spontaneous sequence method and Valsalva manoeuvre in healthy subjects.
AB  - The objective of this study was to compare the baroreflex sensitivity (BRS)
      assessed by the new, non-invasive, spontaneous sequence method (BRS-sequence)
      with the Valsalva manoeuvrebased BRS. Fourteen healthy volunteers were studied in
      the supine position, during 60 degrees head-up tilt (HUT) and during -30 degrees
      head-down tilt (HDT). Blood pressure and R-R intervals were continuously and non
      invasively recorded using a Finapres device. The BRS-sequence was assessed by
      analysing the slopes of spontaneously occurring sequences of three or more
      consecutive beats in which systolic blood pressure and R-R interval of the
      following beat increased or decreased in the same direction in a linear fashion;
      it was compared with data obtained during the Valsalva manoeuvre in each
      position. The time and frequency domain indices of R-R interval variability were
      also evaluated. The mean difference of BRS between the two non-invasive methods
      was 3.86 ms/mmHg with a standard deviation of 9.14 ms/mmHg. BRS was decreased
      during HUT and increased during HDT as assessed by both techniques. The changes
      in BRS were associated with vagal withdrawal and sympathetic activation during
      HUT and enhancement in the cardiac vagal tone and reduction in the sympathetic
      activity during HDT. We conclude that the BRS-sequence technique provides a
      reliable method to study the neural control of the circulation, although the body
      position in consecutive measurements needs to be standardized.

PMID- 9232360
TI  - Systemic and regional (including superior mesenteric) haemodynamic responses
      during supine exercise while fasted and fed in normal man.
AB  - The systemic and regional (including superior mesenteric artery, SMA) responses
      to exercise in the fasting and fed state were studied in ten normal subjects
      before, during and after 9 min of graded supine bicycle exercise on two separate
      occasions, when fasted and after a liquid meal. During exercise, blood pressure
      (BP) and cardiac index rose similarly in both states. Resting SMA blood flow was
      higher when fed (519 (282-619) versus 240 (133-255) ml/min, p < 0.01). SMA blood
      flow fell during exercise in both states, to 98 (63-154) ml/min, p < 0.01 when
      fasted and to 55 (42-149) ml/min, p < 0.01 when fed. SMA vascular resistance rose
      during exercise in both states, but rose less when fasted by 36 (6-57)% versus
      143 (36-240)% (NS). Resting forearm and leg blood flow (FBF and LBF) and vascular
      resistance (FVR and LVR) were similar fasted and fed. FBF and FVR did not change
      after exercise in either state. LBF rose and LVR fell similarly in both states.
      We conclude that in normal subjects, although splanchnic oxygen demand is likely
      to be greater after food, during light to moderate exercise splanchnic
      vasoconstriction contributes to maintenance of BP.

PMID- 9232362
TI  - Orthostatic hypotension in a case with multiple sclerosis.
AB  - A 37-year-old woman with a 5-year history of multiple sclerosis is reported. She
      began having recurrent syncope even in the sitting position; other neurological
      features included hiccup, faciooro-lingual flushing and clumsiness of the hands.
      She had alternating Horner's syndrome, mild hypoalgesia of the right face,
      exaggerated deep tendon reflexes of the upper extremities, decreased deep
      sensation and ataxia of the upper extremities, and incomplete transverse
      myelopathy with a T4 sensory level. Head-up tilt testing confirmed orthostatic
      hypotension with relative preservation of the heart rate increase. Magnetic
      resonance imaging indicated abnormal intensities in the paramedian tegmentum and
      base of the medulla, which may have been additionally responsible for orthostatic
      hypotension. Steroid pulse therapy and L-threo-3,4-dihydroxyphenylserine caused
      regression of brainstem signs and reduced syncopal attacks.

PMID- 9232363
TI  - Changing delivery methods for obstructive lung diseases.
AB  - There are three types of modalities for production of aerosolized medications,
      but numerous specific devices using these techniques are available. The
      recognition that children and adults need to use optimal methods to derive
      maximum therapeutic benefit with minimal side effects has resulted in recent
      developments such as spacers for pressurized metered-dose inhalers and breath
      actuated dry powder inhalers and nebulizers. These methods provide finer aerosols
      that can be readily inhaled and deposited in the lung with improved efficiency.
      Delivery systems designed specifically for particular formulations have generally
      been well studied, but there is a paucity of information from manufactures
      characterizing the drug aerosols available from their devices. Clinicians are
      guided by data from drug trials, but must also be furnished with details of the
      delivery systems to allow them to compare devices and make intelligent choices
      for their patients. The material presented in this review provides an evaluation
      of some of the systems currently available for treating asthma and other lung
      diseases as well as a discussion of devices planned for the future.

PMID- 9232361
TI  - Haemodynamic and hormonal effects of two different oral glucose loads in normal
      human subjects.
AB  - Systemic and regional haemodynamics and hormonal responses to two isovolaemic,
      iso-osmotic solutions of 0.5 and 1.0 g/kg of glucose were compared in ten normal
      young subjects (mean age 24 +/- 3 years). Measurements were made while subjects
      were supine before glucose and every 15 min for 60 min after ingestion of each
      solution. Superior mesenteric artery (SMA) blood flow rose similarly after each
      dose. There were corresponding reductions in SMA vascular resistance after each
      dose but no difference between doses. Pulsatility index of the SMA was lower
      after 1.0 g/kg. There was no change in blood pressure, heart rate, cardiac index
      or forearm muscle blood flow after either dose. Plasma glucose levels rose after
      each dose and were higher after 1.0 g/kg. There was no difference in the plasma
      insulin rise between doses. Plasma levels of noradrenaline and adrenaline did not
      change after either dose. These results suggest that with glucose loads within
      the ranges we used, changes in SMA blood flow are not dose-related and larger
      increases in SMA blood flow or in plasma insulin than we observed are needed to
      reflexly activate cardiac output and raise plasma noradrenaline levels in young
      normal subjects.

PMID- 9232364
TI  - Management of acute respiratory failure in chronic obstructive pulmonary disease.
AB  - Acute respiratory failure in the setting of preexisting chronic obstructive
      pulmonary disease (COPD) is a common reason for hospitalization and results in
      the consumption of a substantial amount of health care resources. In recent
      years, new therapies have been proposed, and new information about older
      therapies has become available. Noninvasive ventilation is finding an important
      place as a means of avoiding tracheal intubation. The role of bacterial infection
      as a frequent precipitant to acute respiratory failure in COPD remains poorly
      defined and presumptive antibiotic therapy remains controversial. Vasodilators of
      the pulmonary circulation have received much attention but so far have been
      disappointing in this situation. The role of several other traditional therapies,
      such as mucolytics and methods of secretion removal, have also been challenged in
      recent years. In this review we focus or recent advances in the assessment and
      management of acute respiratory failure in the setting of pre-existing COPD.

PMID- 9232365
TI  - The role of endotoxin in grain dust exposure and airway obstruction.
AB  - Grain dust exposure is a common cause of respiratory symptoms in grain workers,
      feed mill employees, and farmers. Many of these workers develop wheezing and
      acute and chronic bronchitis symptoms, which can be associated with obstructive
      changes on pulmonary function testing. It has recently been demonstrated that
      grain dust exposure causes neutrophilic airways inflammation and systemic
      symptoms related to release of interleukin-1, tumor necrosis factor, interleukin
      6, and other mediators of inflammation. Although grain dust is a heterogenous
      substance, endotoxin has received the greatest amount of attention as a possible
      cause of the airway inflammation that occurs after grain dust exposure. Although
      endotoxin undoubtedly causes a portion of the changes seen after grain dust
      exposure, it is becoming clear that other substances play a role as well.

PMID- 9232366
TI  - Occupational lung disease and the role of peptide growth factors.
AB  - Occupational lung disease can take many forms, including obstructive airway
      disease, asthma, and restrictive parenchymal fibrosis. It would not be useful to
      attempt an all-encompassing review of such a broad topic, even if one were
      restricted to the most recent literature. Thus, I have chosen a small corner of
      one disease process that relates to work ongoing in my laboratory, ie, the
      potential role of growth factors in the pathogenesis of fibroproliferative lung
      disease. This process is the cornerstone of interstitial pulmonary fibrosis,
      which is caused by inhaling such commonly used materials as asbestos and silica.
      Diffuse interstitial pulmonary fibrosis results from chronic exposures in the
      workplace, and the initial lesions of the fibroproliferative process that
      culminate in interstitial pulmonary fibrosis are readily produced in the
      laboratory by exposing rats and mice. The disease could be mediated by a
      combination of peptide growth factors and cytokines that are expressed at sites
      of lung injury.

PMID- 9232367
TI  - Clinical perspective of inorganic dusts, metals, and fumes exposures.
AB  - Although the clinical presentations of illnesses associated with dusts, metals,
      and fumes exposures remain unchanged, there is increasing insight into the
      mechanisms of these diseases, how these illnesses occur, and what might be
      necessary to alter their natural history. It is discouraging to note that despite
      aggressive measures designed to make workplace environments safe, workers
      continue to develop these preventable illnesses.

PMID- 9232368
TI  - Antileukotriene agents.
AB  - The antileukotriene agents, the first new class of asthma medications introduced
      in two decades, represent a promising new alternative in the continuing search
      for effective and safe therapy for chronic inflammation in asthma. The
      leukotrienes are inflammatory mediators whose effects on asthma include
      bronchoconstriction, increased vascular permeability, and increased mucus
      production. In chronic asthma, regular use of either leukotriene synthesis
      inhibitors or leukotriene receptor antagonists has improved pulmonary function
      and clinical symptoms significantly. Antileukotriene agents appear to be safe and
      well tolerated, although long-term studies will be needed to confirm this.

PMID- 9232370
TI  - New regimens in the management of posttraumatic respiratory failure.
AB  - Many individuals are now surviving their injuries to face the consequences of an
      activated immunoinflammatory system and the complications of supportive therapy.
      The pulmonary system bears the force of this insult. An understanding of the
      epidemiology of acute respiratory failure, as well as a greater knowledge of the
      cellular and subcellular mechanisms by which pulmonary dysfunction occurs, has
      led to novel approaches to the management of acute respiratory failure. It also
      appears that lung injury is caused, or at least exacerbated, by iatrogenic
      insults, such as positive-pressure ventilation. The purpose of this review is to
      discuss the etiology and pathophysiology of acute respiratory failure following
      severe injury and the novel therapeutic approaches. A combination of
      immunomodulating and mechanical ventilation strategies will likely provide the
      most successful approach to reducing the morbidity and mortality associated with
      acute respiratory failure following injury.

PMID- 9232369
TI  - Smoke inhalation is a multilevel insult to the pulmonary system.
AB  - Inhalation injury represents an ongoing threat to patients with thermal injury.
      The magnitude of the disease severity is related to the multilevel insult to the
      pulmonary system. Asphyxiants present in inhaled smoke can compromise oxygen
      delivery, resulting in cell death. Also, early changes in the microcirculation of
      the lung parenchyma, related to polymorphonuclear cell activation and oxygen free
      radical production, are responsible for early pulmonary edema. Perhaps the most
      significant pathologic change caused by smoke inhalation is loss of the
      respiratory epithelium and the formation of tracheobronchial casts. The recent
      application of high-frequency flow interruption ventilation and intrapulmonary
      percussive ventilation has made the largest impact on improved survival in
      patients suffering from smoke inhalation.

PMID- 9232372
TI  - Obstructive, occupational, and environmental diseases.

PMID- 9232371
TI  - Mechanisms of acute lung injury.
AB  - Acute lung injury is the end result of common pathways initiated by a variety of
      local or systemic insults leading to diffuse damage to the pulmonary parenchyma.
      Despite the accumulation of abundant information regarding the physiological and
      cellular basis of lung injury and increasingly sophisticated intensive care, an
      improvement in prognosis has lagged behind. It has become clear that there is not
      one mediator responsible for acute lung injury but rather a complex interplay
      exists between diverse proinflammatory (eg, lipopolysaccharide, complement
      products, cytokines, chemokines, reactive oxygen species, and eicosanoids) and
      anti-inflammatory (interleukin-10, interleukin-1-RA, PGI2) mediators. It is
      essential that we obtain a better understanding of the complexities of the acute
      inflammatory response if we are to successfully intervene to prevent or
      ameliorate tissue injury. The purpose of this review is to summarize recent
      developments that have contributed to our understanding of the basic mechanisms
      of lung injury. We focus on the persistence of the inflammatory response on a
      local and systemic level, including local mechanisms acting within the alveolar
      space regulating synthesis, release, and activation of inflammatory mediators;
      the balance of proteinases and antiproteinases; the abnormalities of surfactant;
      and the potential importance of endogenously released anti-inflammatory
      mediators. It is hoped that the results of these studies will provide insights
      into the pathogenesis of lung injury and lead to novel therapeutic strategies to
      prevent or ameliorate lung injury.

PMID- 9232373
TI  - Relational and overt aggression in preschool.
AB  - This research was designed as an initial attempt to assess relational aggression
      in preschool-age children. Our goal was to develop reliable measures of
      relational aggression for young children and to use these instruments to address
      several important issues (e.g., the relation between this form of aggression and
      social-psychological adjustment). Results provide evidence that relationally
      aggressive behaviors appear in children's behavioral repertoires at relatively
      young ages, and that these behaviors can be reliably distinguished from overtly
      aggressive behaviors in preschool-age children. Further, findings indicate that
      preschool girls are significantly more relationally aggressive and less overtly
      aggressive than preschool boys. Finally, results show that relational aggression
      is significantly related to social-psychological maladjustment (e.g., peer
      rejection) for both boys and girls.

PMID- 9232374
TI  - A developmental investigation of social aggression among children.
AB  - Social aggression consists of actions directed at damaging another's self-esteem,
      social status, or both, and includes behaviors such as facial expressions of
      disdain, cruel gossipping, and the manipulation of friendship patterns. In Study
      1, 4th, 7th, and 10th graders completed the Social Behavior Questionnaire; only
      boys viewed physical aggression as more hurtful than social aggression, and girls
      rated social aggression as more hurtful than did boys. In the 1st phase of Study
      2, girls participated in a laboratory task in which elements of social-aggression
      were elicited and reliably coded. In the 2nd phase of Study 2, another sample of
      participants (elementary, middle, and high school boys and girls) viewed samples
      of socially aggressive behaviors from these sessions. Girls rated the aggressor
      as more angry than boys, and middle school and high school participants viewed
      the socially aggressive behaviors as indicating more dislike than elementary
      school children.

PMID- 9232375
TI  - Relational aggression, gender, and peer acceptance: invariance across culture,
      stability over time, and concordance among informants.
AB  - It has been proposed that overt physical and verbal aggression are more prevalent
      among boys and that covert aggression in the context of interpersonal
      relationships is more typical of girls. The purpose of this study was to
      replicate and extend American research on this topic to Italy. Italian elementary
      school pupils (n = 314) and their teachers provided nominations for aggression
      and prosocial behavior on 2 occasions within a single school year. Both peer and
      teacher nominations were highly stable, though there was very poor concordance
      between them. Peer nominations for both overt and relational aggression were
      linked to peer rejection. Contrary to expectations, boys scored higher than girls
      in both overt and relational aggression. Nevertheless, on the basis of the gender
      composition of extreme groups, the authors conclude that the distinction between
      overt and relational aggression is as useful in facilitating research on
      aggressiveness among girls in Italy as it is in the United States.

PMID- 9232376
TI  - Engagement in gender normative versus nonnormative forms of aggression: links to
      social-psychological adjustment.
AB  - Although many important advances have been made in our understanding of childhood
      aggression in recent years, a significant limitation of prior studies has been
      the lack of attention to the possible moderating role of gender in the links
      between aggression and social-psychological adjustment. To address this issue,
      the author evaluated the adjustment status associated with engagement in gender
      normative versus gender nonnormative forms of aggression for both boys and girls.
      Indexes of social-psychological adjustment assessed included teacher and self
      reports of internalizing and externalizing difficulties (N = 1.166 children 9-12
      years old). Results showed that children who engaged in gender nonnormative forms
      of aggression (i.e., overtly aggressive girls and relationally aggressive boys)
      were significantly more maladjusted than children who engaged in gender normative
      forms of aggression and children who were nonaggressive.

PMID- 9232377
TI  - Mother-child participation in conversation about the past: relationships to
      preschoolers' theory of mind.
AB  - Forty 3.5 to 4.5-year-olds discussed 3 past events with their mothers and
      completed a set of theory of mind tasks indexing their ability to reason about
      conflicting mental representations and their understanding of knowledge.
      Semipartial correlations and analyses of covariance showed that children's theory
      of mind scores were related to their participation in memory conversations,
      independent of age and linguistic skill. The frequency with which mothers
      provided new information was related to children's theory of mind scores,
      although mothers' direct replies to children were generally unrelated to
      children's understanding of mind. This research takes an important step toward
      examining the relevance of theory of mind skills to real-world, social
      interaction. The results have implications for explaining the emergence of
      autobiographical memory.

PMID- 9232378
TI  - Young children's appreciation of the mental impact of their communicative
      signals.
AB  - This work addresses whether 30-month-olds appreciate that their communicative
      signals are being understood (or not) by another person. Infants produce a range
      of behaviors, such as repairing their failed signals, that have been construed as
      evidence that they have an implicit theory of mind. Such behavior could be
      interpreted as attempts to obtain some desired goal rather than as attempts to
      gain listener understanding. This study was designed to separate listener
      comprehension from obtaining a material goal. In 4 conditions, children either
      did or did not get what they wanted and the experimenter understood or
      misunderstood their request. As predicted, children clarified their signal more
      when the experimenter misunderstood compared to when she understood. Regardless
      of whether young children achieved their overt goal, they engaged in behaviors to
      ensure their communicative act had been understood.

PMID- 9232379
TI  - Morphological spelling strategies: developmental stages and processes.
AB  - The spelling of many words in English and in other orthographies involves
      patterns determined by morphology (e.g., ed in past regular verbs). The authors
      report a longitudinal study that shows that when children first adopt such
      spelling patterns, they do so with little regard for their morphological basis.
      They generalize the patterns to grammatically inappropriate words (e.g., sofed
      for soft). Later these generalizations are confined to the right grammatical
      category (e.g., keped for kept) and finally to the right group of words (regular
      verbs). The authors conclude that children first see these spelling patterns
      merely as exceptions to the phonetic system and later grasp their grammatical
      significance. The study included two new measures of grammatical awareness, both
      involving analogies, that predicted success with spelling inflectional morphemes
      in later sessions.

PMID- 9232380
TI  - Infants of depressed and nondepressed mothers exhibit differences in frontal
      brain electrical activity during the expression of negative emotions.
AB  - Studies have shown that infants of depressed mothers express negative emotions
      more frequently than infants of nondepressed mothers. The present study examined
      electrical brain activity during expression of negative and positive emotions in
      infants of depressed and nondepressed mothers. Infants, 11 to 17 months of age,
      were exposed to conditions designed to elicit positive and negative emotions
      while electroencephalographic (EEG) activity was measured from left and right,
      frontal and parietal regions. EEG activity was analyzed when infants were
      displaying prototypic expressions of emotions. Compared with infants of
      nondepressed mothers, infants of depressed mothers exhibited increased EEG
      activation in the frontal but not parietal region when expressing negative
      emotions (unfelt smiles and anger). The two groups of infants did not show
      reliable differences is brain activation during the expression of positive
      emotions (happiness, surprise) or neutral expressions. Compared with infants of
      nondepressed mothers, infants of depressed mothers exhibit greater frontal EEG
      activation during the expression of negative emotions.

PMID- 9232381
TI  - Gender-specific pathways between maternal depressive symptoms, family discord,
      and adolescent adjustment.
AB  - Relations among maternal depressive symptoms, family discord, and adolescent
      psychological adjustment were examined in a sample of 443 middle adolescents and
      their mothers. Histories of maternal depressive symptoms, gathered at 3 occasions
      with 6-month intervals, were related to subsequent adolescent reports of
      depressive symptoms, conduct problems, and academic difficulties for girls but
      not for boys. Mediational tests indicated that girls' greater vulnerability to
      family discord (e.g., marital discord, low family intimacy, parenting
      impairments) accounted for the impact of maternal depressive symptoms on their
      social and emotional adjustment. Analyses suggest that family discord is a strong
      mediator in the development of girls' conduct disturbances and a modest mediator
      of girls' depressive symptoms. Results are discussed within a framework that
      integrates interpersonal models of parental depressive symptoms with the gender
      intensification hypothesis.

PMID- 9232382
TI  - Mediators of gender differences in mathematics college entrance test scores: a
      comparison of spatial skills with internalized beliefs and anxieties.
AB  - This study was designed to investigate whether spatial skill, math anxiety, and
      math self-confidence functioned as mediators of a significant gender difference
      in the Mathematics Scholastic Aptitude Test (SAT-M) among the top third of a
      college-bound sample. Using path analytic techniques, the decomposition of the
      significant gender-SAT-M correlation into direct and indirect effects indicated
      that there were no direct effects of gender on SAT-M. Mental rotation and math
      self-confidence showed indirect effects, mediating the gender-SAT-M relationship;
      math anxiety did not. Of these indirect effects, 36% was mediated by math self
      confidence; 64% by mental rotation. For both these variables, most of the
      mediational effects of the gender-SAT-M relationship did not occur by way of the
      causal pathway leading through geometry grades. Thus, the mediational effects
      cannot simply be attributed to the presence of geometry items on the SAT-M or to
      math self-confidence acquired during prior geometry coursework.

PMID- 9232383
TI  - Infant attachment strategies, infant mental lag, and maternal depressive
      symptoms: predictors of internalizing and externalizing problems at age 7.
AB  - The predictive relations between assessments in infancy and parent- and teacher
      reported behavior problems at age 7 were investigated within a low-income sample.
      Infancy assessments indexed family adversity, parent-infant interaction at home,
      infant attachment, infant anger-distress at home, gender, and cognitive
      functioning. Among children at age 7 identified by teachers as highly
      externalizing, 83% were both disorganized in their attachment behavior in infancy
      and below the national mean in mental development scores at 18 months, compared
      with 13% of nonexternalizing children. Avoidant attachment behavior in infancy
      was associated with later internalizing symptoms rather than with externalizing
      symptoms. The behavior problem data reported by mother suggested the possibility
      of attachment-related biases in maternal report data. The results indicate that
      child mental lag in the context of a disorganized attachment relationship
      constitutes 1 early step on the pathway to school-age externalizing behavior.

PMID- 9232385
TI  - Children's attachment representations: longitudinal relations to school behavior
      and academic competency in middle childhood and adolescence.
AB  - A longitudinal study examined children's (N = 108) attachment representations in
      relation to behavior and academic competency at school during middle childhood
      and adolescence. Attachment representations were assessed from children's
      responses to a separation story at age 7 years. At ages 9, 12, and 15, teachers
      rated children on four dimensions of school behavior: attention-participation,
      extroversion, disruptive behavior, and insecurity about self. Children's grade
      point average (GPA) in school was also examined. Children's attachment
      representations (secure vs. insecure) did not predict either disruptive behavior
      or extroversion, but they were significantly linked to attention-participation,
      insecurity about self, and GPA, with secure representations being associated with
      more favorable outcomes. The study controlled for social class, gender, IQ,
      perspective-taking ability, and prior competency.

PMID- 9232384
TI  - Roles of temperamental arousal and gender-segregated play in young children's
      social adjustment.
AB  - The hypothesis that gender differences in children's adjustment is partially
      influenced by differences in temperament and interactions with same-sex peers was
      examined. Fifty-seven predominantly White, middle-class preschoolers (29 boys and
      28 girls, M age = 54.5 months) participated. Measures were taken of children's
      arousability, problem behaviors, and tendencies to play with same-sex peers. A
      semester later, children's peer status was assessed. Analyses revealed that
      arousability and same-sex peer play interacted to predict problem behaviors. For
      boys high in arousability, play with same-sex peers increased problem behaviors.
      In contrast, arousable girls who played with other girls were relatively unlikely
      to show problem behaviors. Moreover, the interaction of arousability and same-sex
      peer play predicted boys' (but not girls') peer status, and this relation was
      partially mediated by problem behaviors. The role of gender-related processes is
      discussed.

PMID- 9232386
TI  - Economically disadvantaged preschoolers: ready to learn but further to go.
AB  - Cognitive competencies and motivation were assessed in 233 preschool and
      kindergarten children in the fall and again in the spring. Cognitive assessments
      were given again in the spring of the following year (kindergarten or 1st grade)
      to a subsample of 88 children. The results revealed much poorer performance among
      the economically disadvantaged children compared with advantaged children on all
      8 of the cognitive tests. For most cognitive measures, gains were roughly equal
      and the socioeconomic status (SES) differences at the end of 1 or 2 years in
      school were similar to the differences at the beginning of the year. Only a few
      SES differences were found on the motivation measures assessing children's self
      confidence, attitude toward school, expectations for success, dependency, and
      preference for challenge; they did not systematically favor either disadvantaged
      or advantaged children. Classroom observations revealed some differences in
      disadvantaged and advantaged children's classroom behavior.

PMID- 9232387
TI  - The role of the ostiomeatal unit anatomic variations in inflammatory disease of
      the maxillary sinuses.
AB  - OBJECTIVE: The purpose of the study was to determine the correlation between bony
      anatomic variations of the ostiomeatal unit (OMU) and chronic maxillary
      sinusitis. The study was based on the hypothesis that the mucosal contact caused
      by the variations represents the critical factor in increasing the risk of
      maxillary sinusitis. MATERIALS AND METHODS: Thin section high resolution
      computerised tomography (CT) examinations of the paranasal sinuses in 73
      consecutive patients with 113 anatomic variations of the OMU were retrospectively
      reviewed. The following CT features were assessed: (1) Type of anatomic
      variations, (2) presence of a mucosal contact in the OMU and (3) presence of
      maxillary disease. Statistical evaluation was carried out using chi 2-test.
      RESULTS: The following bony anatomic variations were found: Concha bullosa (67
      cases), abnormalities of the uncinate process (18 cases), Haller's cells (24
      cases) and large ethmoidal bulla (four cases). Only 52 of the 113 anatomic
      variations were associated with ipsilateral maxillary disease (mucosal
      thickening, mucous retention cysts, polyps, retained secretions). Of 113
      variations, 44 caused a mucosal contact, 35 of these were associated with
      maxillary abnormalities, while in nine cases there were no pathologic changes. Of
      69 variations, 17 did not cause mucosal contact (P < 0.05). CONCLUSION: Our data
      shows that, in the presence of anatomic bony variations, a contact between the
      mucosal surface of the OMU is valuable in predicting the likelihood of a
      maxillary inflammatory disease.

PMID- 9232388
TI  - Virtual endoscopy of nasal cavity and paranasal sinuses.

PMID- 9232389
TI  - MR of malignant nasosinusal neoplasms. Frequently asked questions.
AB  - This paper focuses on the role of MR imaging of malignant neoplasms through a
      particular layout that emphasizes: (a) the rationale for the application of
      imaging; (b) the factors influencing the selection of sequences, planes and their
      proper arrangement; (c) the correlation between MR findings, imaging staging and
      clinical decision making. Since in most cases surgery is the treatment of choice,
      the precise assessment of the local extent and spread of tumour plays a key role
      in planning the surgical approach and influences either the therapy and the
      prognosis. However, the degree of spatial/anatomical detail required in treatment
      planning significantly differs between surgery and radiotherapy. Planning of the
      examination technique focuses on: (a) assembling sequences and planes in the
      shortest time possible; (b) the solution of specific problems: distinction
      between neoplasm and retained secretions within nasosinusal cavities; staging of
      submucosal spread toward the anterior cranial fossa, the orbit, the pterygo
      palatine and superior orbital fissures. Since the most effective barrier to
      spread of neoplasms beyond sinusal walls does not depend on the mineral content
      of bone, but on the periosteum, assessment of the integrity of periorbita or dura
      mater is an essential information. Although MR cannot detect focal erosions of
      the thin sinusal walls, it reliably demonstrates both residual barriers
      (periorbita and dura), even though the bone has been completely destroyed.
      However, the final decision concerning orbital exenteration is made according to
      intraoperative staging. MR imaging can accurately precise the degree of anterior
      cranial fossa involvement. Furthermore, since either MR and CT accurately
      indicate the need to perform an anterior craniofacial resection and adequately
      exclude neoplastic invasion requiring orbital exenteration, more comparative
      studies are required to demonstrate that MR preoperative staging of nasosinusal
      malignancies is cost-effective.

PMID- 9232390
TI  - Perineural tumor extension along the trigeminal nerve: magnetic resonance imaging
      findings.
AB  - OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) findings of 15
      patients with perineural tumor extension along the trigeminal nerve in
      correlation with clinical data. METHODS: The clinical records and MRI studies of
      15 patients with perineural tumor extension along the trigeminal nerve were
      retrospectively reviewed. Imaging studies included plain and contrast-enhanced
      thin section T1-weighted spin echo (T1-WSE) MRI with and without fat-suppression.
      The studies were compared to determine which sequence provided greatest tumor
      conspicuity and best depiction of tumor extent. The conspicuity of these tumors
      was assessed on the available sequences by two observers by consensus. RESULTS:
      The contrast-enhanced T1-weighted spin echo fat-suppressed images (T1-WSECEFS)
      demonstrated greatest tumor conspicuity and best depiction of tumor extent in the
      extracranial head and neck and skull base region. The conventional T1-weighted
      spin echo pre- and postcontrast images were, however, diagnostic of perineural
      tumor extension in 11 patients due to the presence of considerable tumor bulk and
      extension well above the skull base. In the other four patients the perineural
      tumor was poorly visualized on the conventional T1-WSE images and well visualized
      on the fat-suppressed images. The mandibular division of the trigeminal nerve
      (V3) was most commonly involved (n = 10), followed by the maxillary (V2; n = 5)
      and ophthalmic (V1; n = 2) division. Two patients had both mandibular as well as
      maxillary nerve involvement. The finding of perineural tumor extension had
      significant impact on patient management: based on the MR imaging study, the
      primary tumor was considered inoperable (n = 13), the extent of surgery was
      expanded (n = 2) and radiation therapy (RT) ports were extended (n = 12).
      CONCLUSION: Complete trigeminal nerve imaging is recommended when evaluating
      (suspected) head and neck malignancies with a high risk for perineural extension.
      In these cases thin section axial and coronal precontrast T1-WSE MR images and
      postcontrast T1-WSE MR images with fat-suppression should be obtained. In the
      rare event that artifacts degrade the quality of the fat-suppressed images,
      contrast-enhanced T1-WSE sequences without fat-suppression can additionally be
      used.

PMID- 9232391
TI  - Assessment of parotid masses: which MR pulse sequences are optimal?
AB  - The objective of this paper is to determine which MR pulse sequences are optimal
      for delineation of lesion and predicting pathologic nature of lesion with signal
      intensity. A prospective study was performed in 53 parotid masses (39 benign and
      14 malignant lesions) in 53 patients. Signal intensity of lesion was visually
      assessed and lesion/parotid contrast-to-noise ratios were measured. On visual
      assessment, detection sensitivity was 100% for nonenhanced nonfat-suppressed T1
      weighted images, 91% for nonfat-suppressed fast spin-echo (FSE) T2-weighted
      images, 83% for gadolinium-enhanced fat-suppressed T1-weighted images, and 75%
      for fat-suppressed FSE T2-weighted images. The highest contrast-to-noise ratios
      were obtained with nonenhanced T1-weighted images. Hypointensity of lesion
      relative to the parotid gland on nonfat-suppressed FSE T2-weighted images was
      seen in 11 of 14 malignancies, 12 of 15 Warthin tumors, and two of 18 pleomorphic
      adenomas. Cystic portion of hyperintensity on nonenhanced T1-weighted images was
      solely seen in benign tumors (n = 11). Thus, the highest accuracy (81%) (79%
      sensitivity and 82% specificity) for predicting malignancy was obtained with a
      criterion of hypointensity on nonfat-suppressed FSE T2-weighted images plus
      absence of cystic portion of hyperintensity on nonenhanced T1-weighted images.
      Nonenhanced T1-weighted images combined with nonfat-suppressed FSE T2-weighted
      images is optimal for delineation of lesion and prediction of pathologic nature
      of parotid masses.

PMID- 9232392
TI  - Ultrasonographic evaluation of superficial lymph node metastases in melanoma.
AB  - The aims of the present work were to assess the diagnostic accuracy of
      ultrasonographic evaluation of superficial lymph nodes in patients with cutaneous
      melanoma and to describe the sonographic characteristics which permit early
      detection of neoplastic nodal involvement. Eighty-seven patients (89 lymph node
      sites) were studied for approximately a 3-year period, with a minimal
      surveillance time of 1 year. The ultrasonographic imaging equipment utilized were
      a 10 MHz scanner with a mechanical and one with 10 MHz electronic linear probe.
      The characteristics considered indicative of possible metastatic involvement
      were: round shape (short to long axis ratio > 0.5), no central hilus, nodular
      areas within the lymph node, sinuosity of the lymph node edges and lymph node
      with regular morphology and echostructure but with maximum diameter greater than
      3 cm. Generally inguinal and axillary lymph nodes are larger than cervical ones.
      Of the 89 sites explored, 32 were considered 'suspect'. All 32 of these were
      subjected to cytology using ultrasound-guided, fine needle aspiration. The
      remaining 56 came in for a periodic control examination during a year. Thirteen
      of the 32 'suspect' lymph nodes proved positive at the pathologic examination.
      Two patients whose ultrasound diagnosis was negative developed metastases within
      2 to 4 months (ultrasound false negatives). Our study indicates that there are
      sonographic features indicative of lymph node metastases from melanoma even in
      the early stages of the disease. Ultrasound scanning, therefore, is a useful
      diagnostic tool in the follow-up of melanoma patients, identifying which should
      be subjected to further testing with needle biopsy.

PMID- 9232393
TI  - Nasopharyngeal cavity narrowing associated with posterior maxilla and pterygoid
      plate fracture: report of three cases.
AB  - The CT appearances of three cases with severe nasopharyngeal cavity narrowing are
      described. In all cases the facial trauma was due to a motor vehicle accident.
      These cases demonstrate that posterior maxilla and pterygoid plate fractures can
      cause significant nasopharyngeal soft tissues swelling, most likely due to
      haemorrhage and/or oedema. Severe nasopharyngeal cavity narrowing could cause
      difficulty in elective nasogastric tube and endotracheal tube intubation via the
      nasopharyngeal route.

PMID- 9232394
TI  - Warthin's tumor of the parotid gland with extension into the parapharyngeal
      space.
AB  - A case of Warthin's tumor of the parotid gland which extensively extended into
      the parapharyngeal space is presented. The tumor border against the parotid gland
      was ill-defined but the border towards the parapharyngeal structures was clear.
      Solid portions of the tumor appeared hypointense relative to the gland on both
      unenhanced T1- and T2-weighted MR images without fat suppression, whereas cystic
      portions appeared hypointense on T2-weighted images and hyperintense on
      unenhanced T1-weighted images. Pathologic study showed that the ill-defined
      margin was caused by inflammation and cystic material consisted of highly
      proteinaceous material. We concluded that the atypical extension into the
      parapharyngeal space of the tumor was caused by its location in the deep lobe of
      the parotid gland and its bulky size.

PMID- 9232395
TI  - Infected ossified lingual thyroid goitre.
AB  - Lingual thyroid is a rare embryologic migration failure. It may undergo goitrous
      changes and the ensueing complications as well as carcinomatous transformation
      [1,2]. We describe a case of an infected ossified lingual thyroid goitre with
      suspicion of carcinomatous transformation.

PMID- 9232396
TI  - Digital mammography using storage phosphor plate technique--optimizing image
      processing parameters for the visibility of lesions and anatomy.
AB  - Digital mammograms from a storage phosphor plate system for general radiography
      were compared to conventional mammograms by means of visual grading analysis
      (VGA). For the digital images, image processing parameters were optimized and
      evaluated through observer preference analysis (OPA). The results of the VGA
      showed significantly better gradings for the conventional mammograms for
      parenchyma, linear structures, and cysts, and significantly better gradings for
      the digital mammograms for the skin surface. For calcifications, no significant
      difference was seen. For the OPA, contrast enhanced mammograms graded
      significantly best. Using standard image processing, the digital mammograms were
      considered as adequate for diagnosis in 49% of the cases, as uncertain in 20%,
      and as inadequate in 31%. However, the observers differed considerably in their
      gradings both in the VGA and in the OPA.

PMID- 9232397
TI  - Incidentally discovered adrenal masses: evaluation with gadolinium enhancement
      and fat-suppressed MR imaging at 0.5 T.
AB  - The purpose of the study is to evaluate the ability of Gd-enhancement and fat
      suppressed MR imaging operating at midfield strength to characterize incidentally
      discovered adrenal masses. Sixty patients with 72 adrenal masses incidentally
      discovered during US or CT exams were studied with a 0.51 MR unit following
      clinical and laboratory evaluation. After Gd-DTPA intravenous administration a
      modified three-point Dixon technique was performed in all patients. This
      technique provided three images sets: conventional T1-weighted SE images, fat
      suppressed T1-weighted images and water-suppressed T1-weighted images. Diagnosis
      was established by means of surgery (11 lesions), fine-needle biopsy (21 lesions)
      and stability on ultrasonographic follow-up for at least 1 year (range, 12-87
      months) from adrenal lesion discovery (40 masses). In most of adenomas (n = 55)
      an homogeneous enhancement was observed on postcontrast T1WI; however, 15 out of
      these lesions showed a small focal spot of high intensity in Gd-enhanced fat
      suppressed images. On the contrary, malignant conditions (n = 6) and
      pheochromocytoma (n = 1), all had inhomogeneous signal intensities which were
      relatively higher after Gadolinium injection as compared with the liver. The fat
      suppression technique demonstrated areas of bright signal intensity related to
      high vascularity. The performance of three observers in order to differentiate
      malignant from benign conditions showed sensitivity, specificity, diagnostic
      accuracy, positive and negative predictive values of 100, 88.5, 90, 50 and 100%
      on the basis of gadolinium enhancement only, by utilizing the Dixon technique. In
      conclusion, although Gd-enhancement and fat-suppressed sequence helped correctly
      differentiate among the groups of incidentally discovered adrenal masses, the
      degree of overlap suggests that it is still difficult to characterize individual
      patients. However, the modified three-point Dixon technique after contrast
      material administration appears to be a further capability of midfield MRI in the
      characterization of adrenal tissue.

PMID- 9232398
TI  - Community acquired pneumonia caused by M. tuberculosis--diagnosis with CT.
AB  - A female Somalian patient presenting with a clinical picture compatible with
      community-acquired bilateral lobe pneumonia failed to respond to empirical anti
      microbial treatment. CT of the chest revealed cavitation of the apical segment of
      the right lower lobe, and this feature pointed to the correct diagnosis:
      tuberculous pneumonia, which was eventually confirmed with cultures taken during
      bronchoscopy. This is the first report of the use of chest CT in the diagnosis of
      lower lobe tuberculosis.

PMID- 9232399
TI  - Repositioning of a misplaced ureteral stent with a balloon catheter: technical
      note.

PMID- 9232400
TI  - 'Man-in-the-barrel' syndrome: MRI and SPECT imaging.

PMID- 9232401
TI  - Scoop biopsy of intracaval tumor thrombi: a preliminary report of a minimally
      invasive technique to obtain large samples.
AB  - PURPOSE: The purpose of this study is to safely improve the yield of intracaval
      biopsy. MATERIALS AND METHOD: A co-axial system was composed of an inner catheter
      with a smoothly tapered tip with a shark jaw, and an outer sheath. The biopsy
      procedure consisted of four steps: (1) the tip was stuck into the target thrombi;
      (2) the inner sheath was advanced deeply into the target and the jaw was opened
      within the mass; (3) the outer sheath was advanced to envelope the inner cather;
      (4) then the system was withdrawn. After simulation experiments seven patients
      underwent this scoop biopsy. RESULTS: A simulation experiment proved that this
      technique brought much larger samples with minimal damage of the target surface.
      Seven patients who had been suspected of intracaval tumor thrombi underwent this
      procedure and confidential pathological examination without any complications.
      CONCLUSION: This scoop biopsy procedure was thought to be helpful in obtaining
      large samples safely.

PMID- 9232402
TI  - Reasons for choice of family practice are debated.

PMID- 9232403
TI  - Too many family physicians or not enough?

PMID- 9232404
TI  - When your practice is under the microscope: how to survive a rural preceptorship
      site visit.

PMID- 9232405
TI  - Jane.

PMID- 9232406
TI  - A consortium, graduate medical education, and Buffalo: defining a common ground.
AB  - Regional graduate medical education (GME) consortia are a strategy to align
      public support for GME with societal goals. One such consortium was established
      in Buffalo, NY, to pool financial resources, facilitate processing of
      Accreditation Council for Graduate Medical Education requirements, guarantee
      quality education, and more appropriately use community resources. Cooperation
      has attracted external funding from state and federal governments and private
      foundations, fostering community-wide undergraduate medical education, as well as
      GME. The American Association of Medical Colleges has identified 36 GME consortia
      in the United States. New York may lead the nation on a strategy to use consortia
      for the distribution of all state-appropriated GME support. The relationships
      fostered by consortial interactions have benefitted family medicine and provided
      opportunities for leading regional medical education into a primary care
      specialty balanced future.

PMID- 9232407
TI  - Outdoor-based leadership training and group development of family practice
      interns.
AB  - BACKGROUND AND OBJECTIVES: Current trends in health care demand expanded
      competencies for future physicians, including group process skills that
      traditional medical curricula rarely address. One approach to enhancing group
      dynamics and teaching teamwork skills is outdoor-based experiential learning.
      This study examines the effect of an outdoor-based learning intervention on
      family practice interns' group problem solving, team building, and communication.
      METHODS: Two of 13 programs in the University of Washington Family Practice
      Residency Network included structured, outdoor-based experimental leadership
      training during intern orientation. The other 11 programs served as controls.
      Within 1 month following orientation, surveys were sent to all University of
      Washington Network interns. Respondents completed 27 questions designed to assess
      perceptions of trust, group awareness, group problem solving, group
      effectiveness, and interpersonal communication within an intern class. RESULTS:
      The survey response rate was 85%. Study and control groups were not significantly
      different with respect to age or gender. The study group scored higher on all
      individual questions and variables, with statistically significant differences on
      10 questions and three variables. CONCLUSIONS: Experiential, outdoor-based
      leadership training may positively influence intern class group formation and
      development. Experiential training early in residency may reduce intern stress by
      accelerating intra-class relationships and may represent a foundation on which to
      build effective group process curricula for residents.

PMID- 9232408
TI  - Incremental change in student knowledge during a third-year family medicine
      clerkship.
AB  - BACKGROUND AND OBJECTIVES: Family medicine clerkships compete with other clinical
      experiences for a limited amount of available curricular time. The overlap of
      clinical material covered by other departments raises the possibility that
      students will realize increased or diminished added value from a family practice
      rotation if they take it later in the third-year schedule. METHODS: All students
      (n = 420) in a required third-year clerkship in two geographically distant
      medical schools completed pre- and post-clerkship multiple choice examinations on
      the clinical content of family practice. School A has a lock-step schedule; all
      the clinical rotations are taken in a specific order by all students. School B
      has a random schedule. These examinations were random samples, stratified by
      clinical subject area, from the Exam. Kit database, based on the text Essentials
      of Family Medicine, Second Edition. The difference between the pre- and post
      clerkship scores determined the incremental performance. RESULTS: There was no
      significant change in incremental performance over the course of the year at
      either school. CONCLUSIONS: The increased fund of knowledge acquired during a
      family medicine clerkship, as measured by a multiple choice examination, is not
      diminished by prior clinical clerkships in other specialties.

PMID- 9232409
TI  - Family practice residency behavioral science training: influence on graduate
      practice activity.
AB  - BACKGROUND AND OBJECTIVES: The educational efficacy of family practice residency
      behavioral science training and how various educational approaches might
      influence graduate practice activity are poorly understood. In this study, we
      compare a traditional didactic and clinical block rotation approach to a problem
      based learning (PBL) and clinical, experiential behavioral science curriculum.
      METHODS: Surveys of pre- and post-intervention cohorts were used to assess
      graduates' perceptions of their understanding of broad behavioral science
      concepts, their competence to manage specific behavioral conditions, and their
      behavioral science practice activity. The two cohorts were University of
      California, Irvine family practice residency program graduates from 1984-1988
      (58) and residency graduates from 1993-1995 (27). American Board of Family
      Practice (ABFP) In-service Training Examination scores were also compared.
      RESULTS: No significant differences were detected in self-perceived competence
      and ABFP examination performance. Residency graduates in the post-intervention
      cohort more often included depression, marital counseling, and eating disorders
      in their practice and reported more frequent practice activity for situational
      stress and sexual dysfunction. The post-intervention group reported less
      involvement with alcohol and substance abuse problems. This group also reported
      practice activity that exceeded perceived levels of competence for attention
      deficit disorder, learning disorders, and eating disorders. CONCLUSIONS:
      Participants in a PBL-clinical experiential curriculum reported higher levels of
      practice activity for several common behavioral problems. It seems unlikely that
      these differences were due to curriculum changes. Further investigation of the
      influence of educational and other factors on residency graduate practice
      activity is needed.

PMID- 9232410
TI  - The reading habits of family practice residents.
AB  - BACKGROUND AND OBJECTIVES: Little is known about the reading habits of family
      practice residents. This study describes the reading practices of family practice
      residents, including how much time they spend reading and what information
      sources they use, identifies factors that may be used by educators to stimulate
      resident reading, and identifies factors that may inhibit or discourage reading.
      METHODS: A questionnaire about reading habits was mailed to 613 randomly selected
      resident members of the American Academy of Family Physicians in March 1994.
      RESULTS: Of 613 questionnaires sent, 314 (51%) were completed and returned.
      Participants reported reading an average of 3.7 hours per week and were most
      often motivated to read to obtain information related to clinical cases or to
      prepare for an upcoming presentation. Pocket manuals were the most frequently
      read and original scientific research the least frequently read sources of
      medical information. Fatigue and family responsibilities were the factors most
      important in preventing reading. Year in residency, moonlighting hours, age,
      gender, or household size were not associated with reported reading time.
      CONCLUSIONS: Clinical cases and upcoming presentations may be the best motivators
      of resident reading. Training programs need to continue to develop strategies to
      minimize resident fatigue, which may lead to increased reading among trainees.
      The importance of original scientific research articles during residency training
      is unclear.

PMID- 9232411
TI  - Evaluating domestic partner abuse in a family practice clinic.
AB  - BACKGROUND AND OBJECTIVES: Although national surveys indicate that approximately
      2 million women are victims of severe physical aggression by their partners each
      year, these women are underidentified by physicians. The assessment by medical
      personnel of partner abuse is hampered by lack of a simple and reliable
      instrument that systematically and quickly determines the occurrence and effect
      of abuse among patients. METHODS: Ninety (58% of an eligible pool) consecutive,
      consenting, eligible female patients at a suburban family practice clinic at a
      tertiary university hospital completed the Partner Abuse Interview to evaluate
      the 1-year prevalence and effect of abuse. RESULTS: The Partner Abuse Interview
      required as little as 3 minutes to administer. Results obtained with the
      interview instrument were internally consistent. Interrater reliability was high
      for the diagnosis of partner relationship problems with physical abuse by males,
      as reported by females. Approximately 15% of the women reported having sustained
      injury or being fearful of their partners as a result of their partners' physical
      aggression in the past year. CONCLUSIONS: The Partner Abuse Interview is a simple
      and reliable instrument that could be adapted for use by medical personnel to
      assess incidents of abuse among patients.

PMID- 9232412
TI  - Integration of mental health and medical records: practices and opinions of
      behavioral scientists.
AB  - BACKGROUND AND OBJECTIVES: This study provides information from a national sample
      of behavioral scientists about their practices and opinions about placement of
      mental health notes in the general medical record. METHODS: Using a mailed
      survey, behavioral scientists in US family practice residencies responded to
      questions about the location of mental health notes, the rationale for placement
      of notes, and opinions about integration of mental health notes into general
      medical records. RESULTS: The majority (71.8%) of behavioral scientists record
      mental health notes in the main body of the patient's medical chart, integrated
      with physician notes. Most respondents favor an integrated record to increase
      collaboration with medical providers. A variety of methods are used to minimize
      the chance of violating patient confidentiality. CONCLUSIONS: Although a majority
      of behavioral scientists integrate mental health notes in the medical chart and
      favor the practice of doing so, there is no consensus about this practice as
      reflected by divergent views and record-keeping methods.

PMID- 9232413
TI  - Focus groups: a useful tool for curriculum evaluation.
AB  - BACKGROUND AND OBJECTIVES: Focus group interviews have been used extensively in
      health services program planning, health education, and curriculum planning.
      However, with the exception of a few reports describing the use of focus groups
      for a basic science course evaluation and a clerkship's impact on medical
      students, the potential of focus groups as a tool for curriculum evaluation has
      not been explored. Focus groups are a valid stand-alone evaluation process, but
      they are most often used in combination with other quantitative and qualitative
      methods. Focus groups rely heavily on group interaction, combining elements of
      individual interviews and participant observation. This article compares the
      focus group interview with both quantitative and qualitative methods; discusses
      when to use focus group interviews; outlines a protocol for conducting focus
      groups, including a comparison of various styles of qualitative data analysis;
      and offers a case study, in which focus groups evaluated the effectiveness of a
      pilot preclinical curriculum.

PMID- 9232414
TI  - Support and rewards for scholarly activity in family medicine: a national survey.
AB  - BACKGROUND AND OBJECTIVES: This survey examined how time is allotted for family
      medicine faculty to pursue scholarly activities and how these activities are
      rewarded. METHODS: A survey was sent to all directors of family practice
      residency programs (n = 373) and chairs of family medicine departments (n = 112).
      Four primary questions were asked: 1) How is faculty time allotted for scholarly
      activities? 2) Does the residency or department use an explicit reward system? 3)
      What activities are rewarded? and 4) What rewards are used? RESULTS: A total of
      363 surveys were returned, for a response rate of 75%. Forty-nine percent of
      respondents have regular, protected faculty time for scholarly activities.
      Faculty at university-based residencies and departments were more likely to have
      protected time (68/93, 73%) than faculty at community-based residencies (93/238,
      39%). Thirty-eight percent of respondents have an explicit reward system.
      Activities rewarded and rewards used are department and program-type specific.
      CONCLUSIONS: Only 39% of community-based residencies and 73% of university
      programs allot regular protected time for faculty. The majority of programs and
      departments do not have an explicit reward system. Further studies are needed to
      determine if the use of protected time and reward systems enhance scholarly
      productivity.

PMID- 9232415
TI  - Teaching tips for clinical faculty from the Zen tradition.
AB  - BACKGROUND AND OBJECTIVES: Teachers of family medicine may improve their skills
      by examining teachers from other disciplines and cultures. The teaching
      traditions of Zen might be adapted to medical education. Zen teachers work to
      eliminate restrictive preconceptions about themselves, their teaching roles, and
      their students. They strive to encounter their students with their minds and
      their perceptions clear and to remain ever open to moments of spontaneity and
      creativity. Examples of how these principles may be used in medical education are
      presented.

PMID- 9232416
TI  - Intracellular signaling and endosomal trafficking of immunoreceptors. Shared
      effectors underlying MHC class II-restricted antigen presentation.
AB  - The cells of the immune system express a wide variety of receptors, defined as
      immunoreceptors because they are involved in antigen recognition. B and T
      lymphocytes express clonally distributed receptors which recognize either soluble
      antigens, through B-cell receptors (BcR), or peptides associated to major
      histocompatibility complex (MHC) molecules, through T-cell receptors (TcR). Many
      lymphoid or myeloid cells, such as B lymphocytes, macrophages or dendritic cells,
      express receptors for antigen-antibody complexes, which recognize the Fc portion
      of immunoglobulins (FcR). Although their ligands are different, immunoreceptors
      share both structural and functional homologies. The BcRs, TcRs and most FcRs,
      are multichain complexes composed of a ligand binding module, including one or
      two chains which determine the specificity of antigen recognition and a
      transducing module, which includes two to six chains containing a conserved motif
      in their cytoplasmic tail (A.D. Keegan and W.E. Paul, Immunol. Today 13 (1992) 63
      68). This motif, called ITAM for immunoreceptor tyrosine-based activation motif
      (M.G. Reth, Nature 338 (1989) 383-384 and J.C. Cambier, Immunol. Today 16 (1995)
      110-114) consists of five conserved amino acid residues precisely spaced over an
      amino acid sequence (D2xY2xL7x2xL). ITAMs couple receptors to intracellular
      effectors which induce a cascade of events leading to both cell activation and to
      down regulation of the receptors. This review focuses on recent data supporting
      the involvement of cytosolic effectors of cell activation in the endosomal
      transport of immunoreceptors. The possible role of these cytosolic factors in
      lysosomal transport and MHC class II restricted antigen presentation is
      discussed.

PMID- 9232417
TI  - T-cell development in the absence of the pre-T-cell receptor.
AB  - The development of pre-T-cells with productive T-cell receptor beta (TCR beta)
      rearrangements can be furthered by each of the pre-T-cell receptors (pre-TCR),
      the alpha beta TCR as well as the gamma delta TCR, albeit by distinct mechanisms.
      While the gamma delta TCR affects CD4-8- precursor cells irrespective of their
      TCR beta rearrangement status both the pre-TCR and the alpha beta TCR select only
      cells with productive TCR beta genes for expansion and maturation. The alpha beta
      TCR is much less effective than the pre-TCR because of the paucity of TCR alpha
      proteins in TCR beta positive precursors.

PMID- 9232418
TI  - Defective T-cell receptor gamma gene rearrangement in interleukin-7 receptor
      knockout mice.
AB  - T-cell receptor (TCR) genes need to be rearranged by a site specific-VDJ
      recombinase before they are expressed. This process, initiated in CD44+25+
      thymocytes, takes place during the early stage of T-cell differentiation in the
      thymus. Interleukin-7 receptor alpha chain knockout (IL-7R-/-) mice are severely
      deficient in B-lymphocytes and alpha beta T-cells and completely lack the gamma
      delta T-cell lineage. Thymocyte development is arrested at a very early stage (DN
      CD44+CD25-). Because this arrest is earlier than in mice with a block in VDJ
      recombination, we examined the rearrangement status of TCR genes in thymocytes
      from IL-7R-/- mice. The TCR beta locus showed a nearly normal pattern of VDJ
      rearrangements, consistent with the presence of alpha beta T-cells in these mice.
      However, TCR gamma locus rearrangement was absent or severely reduced for all the
      V gamma genes analyzed (V gamma 3, V gamma 4, V gamma 1.1, V gamma 1.2 and V
      gamma 2). In contrast, the delta locus showed little reduction in rearrangement.
      The defect in gamma rearrangements in IL-7R-/- thymocytes is not simply due to an
      absence of mature gamma delta T-cells, since TCR delta-/- mice, which also have
      only alpha beta T-cells, had normal levels of gamma and delta rearrangements.
      These findings indicate that one or both of the two known ligands of IL-7R, IL-7
      and thymic stromal lymphopoietin (TSLP) serves as an extrinsic signal to
      specifically rearrange the TCR gamma locus.

PMID- 9232419
TI  - Peptide mimics of a conformationally constrained protective epitopes of
      respiratory syncytial virus fusion protein.
AB  - AIMS: To identify peptides that mimic (mimotopesi conformational and protective
      epitopes of RSV fusion protein and to assess their efficacy as immunogens and
      potential vaccines. MATERIAL AND METHODS: An 8-mer solid-phase (TG resin) library
      was screened with a neutralising and protective RSV fusion protein specific
      monoclonal antibodies (Mab-19). After selection of positive beads, reactive
      sequences were identified by microsequencing and 8-mer peptides were synthesised.
      Improvement of binding was analysed by amino acid replacement using the SPOTs
      method. RESULTS: Mabs were not able to bind to the free and soluble peptides, nor
      did these peptides induce anti-RSV specific antibodies. However, several peptides
      re-synthesised on a TG resin (to produce de-protected 8-mer peptides linked to
      the resin) or as SPOTs reacted specifically. Therefore it was critical to be able
      to reproduce this conformation in order to use these mimotopes as immunogens and
      potential vaccines. Using C-terminal constrained versions of the mimotopes,
      strong binding of one of the Mabs to the peptides was demonstrated by surface
      plasmon resonance. Immunisation of Balb/c mice with these peptide-mimics produced
      anti-sera that: (1) reacted specifically with RSV; (2) inhibited the binding of
      the Mab to the virus; (3) neutralised RSV in vitro with high titres (range: 80
      640); and (4) reduce significantly the viral load in the lungs of mice challenged
      with RSV (P < 0.01). CONCLUSIONS: This report demonstrates for the first time
      that: (1) a protective epitope of the conserved RSV fusion protein can be
      mimicked by synthetic peptides; and (2) immunisations with these mimotopes
      induced specific anti-RSV neutralising antibodies and reduced viral load in vivo.
      These results represent a novel concept for the development of a vaccine against
      RSV.

PMID- 9232420
TI  - Gene therapy with recombinant adenovirus vectors: evaluation of the host immune
      response.
AB  - E1, E3-deleted, replication-deficient recombinant adenoviruses are widely studied
      as vectors for their capacity to transfer therapeutic genes in vivo. They can
      infect a wide variety of dividing and quiescent cells from different organs and
      possess a large packaging capacity. One of the major limitations in the use of
      these vectors for gene therapy is the transient expression of the transgene in
      vivo and the poor transduction efficiency when re-administered. Despite the
      deletion of the viral E1 region, low level of early and late viral genes are
      expressed in vivo. Thus, viral antigens plus those derived from transgene
      expression in transduced cells contribute to cellular immune responses leading to
      the destruction of these cells. Production of anti-adenovirus antibodies, the
      cellular immune response as well as the early non-specific clearance of the
      vectors, constitute barriers to successful gene therapy. New vectors have been
      derived with additional deletions in the E2a or the E4 regions. Such second
      generation vectors were evaluated in vivo. These studies have revealed the
      complexity of the immune mechanisms elicited by these vectors and the importance
      of several parameters in these evaluations (i.e. mouse strains, nature of the
      transgene, route of administration...). In order to inhibit the production of
      neutralizing antibodies to adenovirus that prevent from further readministration
      of the vectors, immunosuppressive strategies were undertaken. Treatment regimens
      with immunosuppressive drugs (cyclophosphamide, FK506) or with monoclonal
      antibodies that block either the T cell receptor or costimulation pathways allow
      prolonged transgene expression and/or readministration of adenoviral vectors. In
      addition, transduction efficiencies may be increased by transiently inhibiting
      non-specific immune mechanisms that lead to the dramatic early clearance of the
      vectors. Taken together, these strategies may improve further gene therapy
      protocols by decreasing the host immune response to adenoviral vectors.

PMID- 9232421
TI  - Granulocyte signal transduction and priming: cause without effect?

PMID- 9232422
TI  - T-cell anergy induced by antigen presenting cells treated with the hemolysin of
      Listeria monocytogenes.
AB  - Antigen presenting cells (APC) that are infected with listeriolysin (LLO)
      secreting Listeria lack the ability to stimulate MHC class II restricted T-cells
      by conventional antigens. Similarly, T-cell activation by native proteins but not
      by peptides was inhibited upon pretreatment of APC with purified listeriolysin.
      The inhibition is due to an irreversible inactivation of T-cells that recognize
      antigen on infected or LLO treated APC. Inhibition was found to dominate over
      stimulation by peptides. This condition is reminiscent of T-cells inactivation by
      antagonistic peptides and represents a novel type of immune escape.

PMID- 9232423
TI  - IL-12 enhances proliferation of peripheral blood mononuclear cells from Chagas'
      disease patients to Trypanosoma cruzi antigen.
AB  - Chagas' disease is caused by infection with Trypanosoma cruzi. Patients in the
      chronic phase of infection were grouped as belonging to the asymptomatic (or
      indeterminate), cardiac and cardiac plus digestive forms. Previous studies have
      described abnormal immune responsiveness by peripheral blood mononuclear cells
      (PBMC) from chronic chagasic patients. We report significant parasite antigen (T
      Ag)-stimulated PBMC proliferative responses to be present in all three groups of
      patients. Treatment of T-Ag-stimulated cultures with rIL-12 significantly
      amplifies proliferative responses in all patients' groups, with similar rates of
      increment. IL-12 enhances T-Ag-specific lymphoproliferation without increasing
      proliferation of unstimulated PBMC from normal individuals or from patients.
      Comparatively, treatment with rIL-2 enhances both T-Ag-specific and unstimulated
      proliferation by PBMC from patients and normals. Thus, IL-12 acts on pre
      activated cells while IL-2 also stimulates resting cells. No synergism was
      obtained by the combined use of IL-12 and IL-2. Therefore IL-12 can act as a more
      selective amplifier of T. cruzi reactive cells than IL-2. IL-12, by enhancing
      parasite-antigen specific immunity, could be of potential therapeutic use to
      control reactivated T. cruzi infections concomitant to AIDS or other situations
      of immunosuppression.

PMID- 9232424
TI  - Products from mast cells influence T lymphocyte proliferation and cytokine
      production--relevant to allergic asthma?
AB  - In IgE allergic diseases both mast cells and T lymphocytes play an important
      role. Whereas mast cels have been implicated in immediate allergic responses, T
      lymphocytes mediate subsequent late phase responses and chronic inflammation.
      Here we review possible links between the early mast cell activation and the
      later T lymphocyte stimulation. Products from mast cells were found to exert
      effects on T lymphocytes. Human Mast Cell line-1 (HMC-1) mast cells modulated
      proliferation and cytokine production of a human CD8+ T-cell clone in vitro.
      Activated mast cells seemed to drive this CD8+ T-cell clone towards a more
      pronounced T (helper) 1 type of response, simultaneously decreasing T-cell
      numbers. It is hypothesized that this might be a negative feed back mechanism
      operating in allergic subjects, by which the Th2-driven IgE production and
      eosinophilia are counteracted.

PMID- 9232425
TI  - Potential deleterious effect of anti-viral cytotoxic lymphocyte through the CD95
      (FAS/APO-1)-mediated pathway during chronic HIV infection.
AB  - The potential deleterious effect through a CD95-based pathway of anti-viral
      cytotoxic lymphocyte (CTL) during HIV-infection was studied. The present paper
      reports that a Nef specific CTL line derived from an HIV-infected person is able
      to kill not only Nef-expressing target cells but also CD95+ compliant Jurkat
      cells. The two mechanisms of cytotoxicity, i.e. perforin-vs-CD95-dependent were
      differentiated according to their respective Ca(2+)-dependence. The existence of
      the dual killing machinery in the anti-HIV CTL line was correlated with the
      coexpression in these cells of perforin and CD95-L molecules. A model of AIDS
      pathogenesis involving the deleterious effect through the CD95 pathway of the
      viral specific CTL response is discussed.

PMID- 9232426
TI  - Anti-acetylcholine receptor Fab fragments isolated from thymus-derived phage
      display libraries from myasthenia gravis patients reflect predominant
      specificities in serum and block the action of pathogenic serum antibodies.
AB  - Myasthenia gravis (MG) is a prototype antibody-mediated autoimmune disease in
      which antibodies against nicotinic acetylcholine receptors (AChR) induce loss of
      functional receptors at the neuromuscular junction. Germinal centers present in
      MG hyperplastic thymus contain activated B-cells spontaneously producing anti
      human AChR (huAChR) Ab in vitro. In order to access the anti-huAChR repertoire
      phage display Fab libraries of thymic lymphocytes were constructed from two MG
      patients. A total of four Fabs highly specific for huAChR were isolated that bind
      to determinants in or near the main immunogenic region (MIR). These anti-huAChR
      Fabs showed evidence of significant somatic mutations supporting the notion that
      the anti-huAChR Ab response in MG patients is driven by antigen. A total of two
      Fabs were able to inhibit up to 90% of donor serum anti-huAChR antibodies.
      Competition with serum anti-huAChR Ab was also observed in unrelated MG patients
      and indicate that anti-huAChR Fabs bind to epitopes on huAChR recognized by the
      majority of MG patients. In vitro antigenic modulation studies demonstrated that
      anti-huAChR Fabs were able to induce AChR loss when cross-linked by an anti-Fab
      antibody but not as monovalent Fab. Moreover, anti-huAChR Fabs were able to
      protect against AChR loss by antigenic modulation induced by MG serum antibodies
      suggesting a potential therapeutic role for these recombinant Fabs in patients
      with a myasthenic crisis.

PMID- 9232427
TI  - Dynamics of HIV variants and specific cytotoxic T-cell recognition in
      nonprogressors and progressors.
AB  - Infection with the human immunodeficiency virus (HIV) results in a disease
      characterized by a rapid viral replication, immunodeficiency and chronic immune
      activation. The vigorous polyspecific cytotoxic T-cell (CTL) response directed
      against multiple HIV epitopes reduces HIV-infected cell numbers, although unable
      to eradicate the virus. The plasticity of the specific CTL repertoire ensures
      adaptation to the high rate of viral variation that can be found in CTL epitopes
      of several HIV-1 proteins. However, viral persistence occurs despite continuous
      CTL recognition and although functional importance of conserved sites in the
      different HIV proteins may impose constraints to viral variation. In the reverse
      transcriptase (RT) which is a major target for antiretroviral therapy, the impact
      of the continuous pressure of drug therapy is more obvious than that of the CTLs.
      Shifts in immunodominant RT regions seem to allow the maintenance of the HIV-1 RT
      CTL recognition with disease progression and antiretroviral therapy. In respect
      to new highly active drug combinations, understanding the capacity of virus
      specific CTLs to control residual viral variants seems very important and may
      allow development of efficient immunotherapies to prevent drug-induced viral
      resistance.

PMID- 9232428
TI  - Generation of heat shock protein-based vaccines by intracellular loading of gp96
      with antigenic peptides.
AB  - Several studies have shown that immunization with heat shock proteins (HSPs)
      purified from tumors of virus-infected cells induces specific cytotoxic T-cell
      (CTL) activity. This immune response is directed against peptides bound to the
      HSPs rather than against the HSPs themselves. The peptides are derived from tumor
      or virus-specific proteins which are degraded in the course of normal protein
      turnover and processing for presentation by MHC class I molecules. The HSPs
      appear to function as carriers for the antigenic peptides. Upon immunization they
      ensure their uptake by specialized macrophages and their introduction into the
      MHC class I presentation route which is otherwise accessible only for
      intracellular proteins. Using influenza virus nucleoprotein (NP) as a model
      antigen, we have tested whether an HSP-based vaccine can be preduced by
      overexpressing an antigen in cultured cells prior to purification of the HSP's.
      The transfection system based on the Semliki Forest virus (SFV) replicon was
      employed to achieve high expression of NP. Since SFV-mediated transfection of
      murine cells was inefficient we used the hamster-derived cell line BHK21, which
      can be transfected with 100% efficiency, as a source for NP peptide-loaded gp96.
      The protein was purified from transfected cells and used for first vaccination
      studies. The hamster gp96 preparation was well tolerated in mice, an antibody
      response against the foreign protein was not observed. Preliminary results
      suggest that a cellular immune response against NP was indeed induced. SFV
      transfection is applicable for any known antigen and is therefore considered to
      be an elegant means for the production of HSP-based vaccines capable of inducing
      a cellular immune response.

PMID- 9232430
TI  - The matrix metalloproteinase RASI-1 is expressed in synovial blood vessels of a
      rheumatoid arthritis patient.
AB  - RASI-1 is a novel matrix metalloproteinase which we isolated from an expression
      cDNA library representing the mRNA of an inflamed synovium obtained from a
      patient with rheumatoid arthritis (RA). To investigate the involvement of RASI-1
      in the pathology of RA, we examined synovial specimens from RA patients with
      antibodies directed against an unique RASI-1-derived peptide. In comparison to
      interstitial collagenase, gelatinase A and B, and stromelysin 1, the RASI-1
      expression in the RA-synovium is located mainly in the tunica media of blood
      vessel walls and its synovial localization is not as ubiquitous as that of other
      MMPs. The tissue inhibitor of metalloproteinases (TIMP-1), although also widely
      expressed in the synovium, exhibits strong colocalization with RASI-1 in blood
      vessel walls. While RASI-1 is expressed in blood vessels of the inflamed synovium
      of an RA patient, its expression was not found in control synovial specimens from
      patients with luxation and arthrosis. However, RASI-1 expression can also be
      found in non-inflamed blood vessels of uterine ligaments and skin. RASI-1,
      although its function and substrates are unknown, could be involved in processes
      such as neovascularization and angiogenesis or lymphocyte extravasation and thus
      may participate in joint tissue destruction during RA.

PMID- 9232429
TI  - Early consequences of macrophage-Francisella tularensis interaction under the
      influence of different genetic background in mice.
AB  - The induction, regulation and expression of protective immunity against
      Francisella tularensis LVS infection is dependent on the results of primary
      interaction between the cells of host's immunoregulatory system and the microbe.
      The early events, at least on the side of macrophages, are under the genetic
      control. To determine the impact of genes that might be involved in the control
      of resistance to Francisella tularensis LVS infection, we have used three
      different inbred strains of mice with increasing resistance to this infection in
      order C3H/HeJ (Lpsd), C3H/HeN (Lpsn"), and C57B1/10N (Lpsn"). The controlled
      production of IL-10, IFN-gamma, and TNF-alpha coupled with increased production
      of reactive oxygen metabolites during early phase of infection distinguished less
      susceptible C3H/HeN mice from their more susceptible cogenic C3H/HeJ
      counterparts. The enhancement of oxidative metabolism that appeared on day 5
      after the infection of both C3H/HeN and C57B1/10N mice closely correlated with
      increasing resistance of these two strains of mice to Francisella tularensis LVS
      infection. These mice were also capable to reach the highest level of TNF-alpha
      on day 5 after the infection. At the same time interval, only C57B1/10N mice
      produced significantly enhanced level of nitric oxide. Overall, these parameters
      may suggest their possible biological role in early-phase resistance to
      Francisella tularensis LVS infection and their subsequent consequences for
      ultimate control of infection and its clearance.

PMID- 9232431
TI  - In vivo blocking of L-selectin rescues BALB/c mice from fatal Leishmania major
      infection.
AB  - Susceptibility and resistance to experimental Leishmania major (L. major)
      infection in mice are associated with a Th2- or Th1-type response, respectively.
      We have previously shown that immunological events occurring within the first 24
      h after infection in the lymph node (LN) draining the site of parasite challenge
      are critical for the development of either type of T-cell responses. In the
      present study we manipulated these events by preventing the entry of naive
      lymphocytes into the draining LN by injecting BALB/c mice with a single dose of
      the anti-L-selectin mAb MEL-14 one day prior to infection with L. major. In
      contrast to control BALB/c mice, in MEL-14 treated animals the primary lesion
      healed 12 weeks after infection. The parasite load in the spleen and lymph nodes
      of MEL-14 treated mice was significantly reduced. The healing was found to be
      associated with an increased production of IFN-gamma and with a decrease in IL-4
      production by LN cells. We observed a dramatic decrease in cellularity in the
      draining LN in Mel-14 treated L. major-infected mice within the first week of
      infection. Moreover, the cells in the LN of MEL-14 treated mice were highly
      enriched in activated cells as well as in cell influx in the draining LN after
      local L. major infection of BALB/c mice prevents fatal disease. The data suggest
      the MEL-14-induced enrichment of the draining LN in memory and activated cells is
      fundamental for the initiation of a protective Th1-type response.

PMID- 9232432
TI  - A non-XLA primary deficiency causes the earliest known defect of B cell
      differentiation in humans: a comparison with an XLA case.
AB  - We report a detailed comparison of B cell defects in two patients, one XLA and
      one non-XLA. Both had severe agammaglobulinemia with a total absence of CD19+
      cells in the periphery. In the non-XLA case, CD19 expression was also highly
      impaired in the bone marrow, resulting in the absence of both B and preB
      compartments. Early proB cells were present since CD34+CD10+ and some CD19+CD10+
      mostly CD34+ were identified, although diminished. By contrast, in the XLA
      patient the CD34+CD19+ proB cells were increased whereas the CD34-CD19+ preB cell
      population was low. Semi-quantitative RT-PCR analysis performed on mononuclear
      bone marrow cells from the non-XLA patient indicated that lambda-like, VpreB, Rag
      1, Rag-2 and TdT transcripts expressed during proB cell stages were found at
      normal levels whereas E2A, CD10, Syk, Pax-5, CD19, Ig alpha, Ig beta, VH-C mu and
      V kappa-C kappa transcripts characteristic of later stages were severely
      depressed. By contrast in the XLA patient most of these transcripts were observed
      in normal amounts. The phenotype of the non-XLA patient resembles that of Pax-5
      or Ig beta knock-out mice, but since the coding sequence of both cDNAs were shown
      to be normal, the blockage might rather result from an altered regulation of one
      of these genes or from defect of other genes. All these data indicate that the
      non-XLA patient suffers from a new genetic defect that results in an arrest of
      differentiation within the proB cell compartment, before the onset of Ig gene
      rearrangements. From all agammaglobulinemias reported so far, including XLA cases
      and those resulting from C mu gene defects, the non-XLA patient exhibits the
      earliest blockage in the B cell differentiation pathway.

PMID- 9232433
TI  - CD148, a membrane protein tyrosine phosphatase, is able to induce tyrosine
      phosphorylation on human lymphocytes.
AB  - CD148 is a new cluster of differentiation defined in the VI International
      Workshop on Leucocyte Differentiation Antigens. It has been identified as the
      hematopoietic form of a formerly described membrane protein tyrosine phosphatase
      called HPTP eta/ DEP-1. Previous data have demonstrated that this molecule is
      able to give rise to [Ca2+]i increase. In the present work we show its capability
      to induce protein tyrosine phosphorylation in human lymphocytes in spite of its
      intrinsic protein tyrosine phosphatase activity. The induction of kinase activity
      suggests the involvement of some protein tyrosine kinase based signaling pathway.
      The activation of this postulated kinase could be carried out through a direct
      association or via an adapter molecule.

PMID- 9232434
TI  - Relevance of the antibody response against human immunodeficiency virus type 1
      envelope to vaccine design.
AB  - Understanding the antibody response in HIV-1 infection is important to vaccine
      design. We have studied the antibody response to HIV-1 envelope at the molecular
      level and determined the characteristics of neutralizing and non-neutralizing
      antibodies. These antibodies were isolated from phage display libraries prepared
      from long-term seropositive asymptomatic individuals. The HIV-1 envelope is
      presented to the immune system in several antigenically distinct configurations:
      unprocessed gp160, gp120 and gp41 subunits and native envelope, each of which may
      be important in eliciting an antibody response in HIV-1 infection. The antibodies
      tested characteristically had poor affinities for native envelope as expressed on
      the surface of virions or infected cells, but had high affinities against non
      native forms of HIV-1 envelope (viral debris). An exceptionally potent
      neutralizing antibody in contrast, bound native envelope with equivalent or
      somewhat higher affinity than this. This indicates that the antibody response in
      HIV-1 infection is principally elicited by viral debris rather than virions, and
      that these antibodies bind and neutralize viruses sub-optimally. Potential
      vaccines should be designed to elicit responses against native envelope.

PMID- 9232435
TI  - The potential of combinatorial peptide libraries for the identification of
      inhibitors of TNF-alpha mediated cytotoxicity in vitro.
AB  - The use of random peptide libraries has recently received considerable attention
      as a new tool for identifying novel therapeutic molecules. The libraries
      represent an enormous number of peptide sequence displayed either on the virion
      surface of filamentous phage clones or on a solid phase synthetic support. In
      this minireview we summarize our recent findings on the use of combinatorial
      peptide libraries to identify antagonists of the biological activities of TNF
      alpha, a cytokine which plays a key role in immune and inflammatory responses.

PMID- 9232436
TI  - Effect of a CC chemokine receptor antagonist on collagen induced arthritis in
      DBA/1 mice.
AB  - Chemokines are small proteins that selectively activate and recruit leukocytes to
      sites of inflammation. Several of them, including the CC chemokines RANTES, MIP-1
      alpha, MIP-1 beta, MCP-1, and the CXC chemokines IL-8, GRO-alpha, ENA-78 have
      been identified in rheumatoid synovium, implicating a potential role for these
      molecules in rheumatoid arthritis. We have investigated the expression patterns
      of CC chemokine receptors in the joints of mice with collagen-induced arthritis,
      a model for human rheumatoid arthritis. In addition, we have investigated the
      incidence and severity of arthritis in mice receiving administration of
      MetRANTES, a modified chemokine which is a nanomolar antagonist of certain CC
      chemokine receptors. The mRNA expression pattern of the chemokines and their
      receptors in the joints of arthritic mice was investigated using reverse
      transcriptase-PCR and in situ hybridization. An upregulation of the CC chemokine
      receptors mCCR1, mCCR2; mCCR3 and mCCR5 was found in the joints from arthritic
      mice, compared to control animals. In addition, injections of MetRANTES reduced
      the incidence of disease in a dose dependent manner. Furthermore, in MetRANTES
      treated mice that did develop arthritis a significantly lower severity of disease
      was observed compared with control animals. Our data clearly demonstrate a role
      for CC chemokines and their receptors in inflammatory joint destruction and
      support the use of chemokine receptor antagonists as potential tools to control
      inflammatory diseases such as rheumatoid arthritis.

PMID- 9232437
TI  - NKRP1A molecule is involved in transendothelial migration of CD4+ human T
      lymphocytes.
AB  - Among human CD4+ T lymphocytes, 5-20% express the C-type lectin molecule NKRP1A.
      Interestingly, CD4+ NKRP1A+ T lymphocytes express high levels of beta 1 and beta
      2 integrins, thus representing a T lymphocyte subset that can possibly adhere and
      migrate through vascular endothelium. Indeed, resting CD4+ NKRP1A+ lymphocytes,
      differently from the CD4+ NKRP1A- subset, migrated across endothelial cell
      monolayers in a Transwell chamber system. This transendothelial migration was
      strongly reduced after pre-treatment with an anti-NKRP1A monoclonal antibody
      (mAb). In addition, the NKRP1A negative Jurkatt CD4+ T-cell line that had been
      stably transfected with NKRP1A cDNA, migrated more rapidly and efficiently than
      untransfected Jurkatt cells. Finally, mAb-mediated cross-linking of NKRP1A
      molecule in CD4+ T lymphocytes induced the upregulation of the LFA1 Mg2+ binding
      site as well as beta 1 and beta 2 integrin chains. Altogether, these findings
      indicate that NKRP1A molecule is involved in transendothelial migration of
      resting CD4+ T lymphocytes.

PMID- 9232438
TI  - Kinetics of immune functions and virus replication during HIV-1 infection.
AB  - INTRODUCTION: Kinetics of human immunodeficiency virus type 1 (HIV-1) cytotoxic T
      lymphocyte (CTL) responses and viral load were evaluated in HIV-1 infected
      homosexual men who progressed to AIDS within 3-6 years after seroconversion and
      in long-term survivors who remained AIDS-free for > 9 years with normal CD4+ T
      cell counts. METHODS: CTL against four major HIV-1 gene products (i.e. Gag,
      reverse transcriptase (RT), Nef and Env) were expanded in vitro under limiting
      dilution conditions using antigen specific stimulation. CTL activity was measured
      in standard split-well 51Cr-release assay. Viral load was measured both as serum
      HIV-1 RNA levels and frequency of circulating CD4+ T cells productively infected
      with HIV-1. Polyclonal T cell function in vitro was determined in whole blood
      lymphocyte cultures, measuring lymphoproliferative responses to CD3 monoclonal
      antibody. RESULTS: Long-term survival was associated with either persistently
      high or stable low HIV-1 specific CTL responses, accompanied by preserved in
      vitro polyclonal T cell reactivity and low viral load. In progressors, HIV-1
      specific CTL responses were initially generated with similar kinetics as compared
      to long-term survivors. However, with progression to AIDS antiviral CTL activity
      and T cell function deteriorated simultaneously, while viral load increased.
      CONCLUSIONS: Our results are consistent with the hypothesis that HIV-1 specific
      CTL are beneficial through control of viremia to the virologic set-point and
      contribute to maintenance of the asymptomatic phase. However, loss of HIV-1
      specific immune control as part of a more general loss of T cell function is the
      precipitating event in AIDS pathogenesis.

PMID- 9232439
TI  - Reconstitution of B cell subsets in Rag deficient mice by transplantation of in
      vitro differentiated embryonic stem cells.
AB  - In vitro differentiated embryonic stem (ES) cells contain a population which is
      similar to fetal liver pro/pre-B cells on the basis of cell surface antigens and
      cytoplasmic expression of immunoglobin heavy chain. This population was purified
      and transplanted into Rag-1 deficient recipients to characterize its
      developmental potential in vivo. Following intravenous transfer, these cells
      rapidly reconstituted the splenic B but not the T cell compartment.
      Reconstitution was transient, indicating the lack of long-term reconstituting
      capacity. Similar to fetal liver, B-1 type as well as conventional B cells were
      generated, accompanied by high serum IgM levels. Intraperitoneal injection
      generated high numbers of peritoneal B cells, predominately of the B-1a
      phenotype, with poor splenic repopulation and low serum IgM levels. These
      observations suggest the emergence of two different B lineage precursor
      populations during in vitro ES cell differentiation and define a possible role of
      the microenvironment in directing lymphoid development.

PMID- 9232440
TI  - T-cell reactivity to human HSP60 in oligo-articular juvenile chronic arthritis is
      associated with a favorable prognosis and the generation of regulatory cytokines
      in the inflamed joint.

PMID- 9232441
TI  - Regulation of macrophage gene expression following invasion by Mycobacterium
      tuberculosis.
AB  - INTRODUCTION: Mycobacteria are intracellular pathogens which survive and grow in
      host macrophages. M. tuberculosis bacilli enter the macrophage via binding to
      several distinct cell surface molecules. Following phagocytosis, sustained
      intracellular bacterial growth depends on the ability to avoid destruction by
      macrophage-mediated host defences such as lysosomal enzymes, reactive oxygen and
      the reactive nitrogen intermediates. We used differential display reverse
      transcription polymerase chain reaction (DD RT-PCR) to identify host genes which
      are regulated during infection and hence which might be involved in the host
      parasite cross talk. RESULTS: Live M. tuberculosis (strain H37Rv) was used to
      infect Balb/c peritoneal murine macrophages. mRNA from infected and uninfected
      macrophages was isolated at different time intervals after phagocytosis and
      subjected to DD RT-PCR. Oligo dT12NV and random 10mer primers were used for PCR
      amplification of cDNA. Macrophage genes which appeared to be differently
      regulated during infection were subjected to further reamplification by PCR in
      order to clone and sequence them. The differential expression of the selected
      bands was further analysed by an RNA protection assay and a Northern blot.
      RESULTS: Several differentially regulated bands were identified. One band, of 158
      bp, was down regulated after infection. Sequencing of this band revealed a high
      level of homology (95% identity) to mouse cytochrome c oxidase subunit VIIc. The
      downregulation was specific for live virulent Mtb, while live BCG, heat killed
      Mtb and latex beads-mediated phagocytosis did not affect the transcriptional
      level of this enzyme. CONCLUSIONS: The cytochrome oxidase enzyme complex of the
      inner mytochondrial membrane catalyzes the reaction between ferrocytochrome c and
      oxygen. The reaction is the terminal event in the electron transport scheme.
      Downregulation of cytochrome c oxidase subunit VIIc could interfere with: (1) the
      host apoptotic programme; or (2) the host respiratory burst.

PMID- 9232442
TI  - Nitric oxide production by macrophages stimulated by antigen-binding T-cell
      factors.
AB  - Contact sensitivity to small molecular weight compounds is accompanied by the
      production of antigen-specific T-cell factors (TCF) shortly after skin
      application of the sensitizing agents. In this study, we show that macrophages
      can be activated by these TCF to generate large amounts of nitric oxide (NO).
      Incubation of the murine macrophage cell line J774 for 24 h with TCF raised
      against dinitrofluorobenzene (DNFB) or picryl chloride (PCL) resulted in a
      nitrite accumulation in the culture medium. Priming of J774 with rIFN-gamma
      synergistically enhanced stimulation of NO synthesis by DNFB-F and PCL-F. A
      possible contribution of lipopolysaccharide (LPS) as a contaminant of the TCF was
      excluded. The enhanced production of NO after stimulation with TCF was
      accompanied with an increased expression of inducible NO synthase. Inclusion of
      inhibitors of protein tyrosine kinase and protein kinase C inhibited the TCF
      induced NO production by macrophages, indicating the involvement of both protein
      kinases in the signaling pathway activated by TCF. Since NO is an important
      biological mediator with many immunoregulatory properties, our results suggest a
      potential role for increased NO production by macrophages in the elicitation of
      contact sensitivity to small molecular weight compounds.

PMID- 9232443
TI  - Selective in vivo deletion of alloactivated TH1 cells by OKT3 monoclonal antibody
      in acute rejection.
AB  - The OKT3 monoclonal antibody (mAb) recognizing the CD3 complex on human T-cells
      has been shown to be an effective immunosuppressive agent for the treatment and
      the prevention of acute rejection episodes in allograft recipients [1]. Following
      the initial doses of OKT3 mAb, activation of T lymphocytes and monocytes is
      observed. This is accompanied by a massive cytokine release, particularly
      following the first injection. The mAb opsonizes the circulating T-cells and the
      coated cells disappear quickly from circulation. OKT3 mAb is commonly
      administered for 5-10 days. The manifestation of side effects weeks
      (cytomegalovirus infection/disease, bacterial and fungal infections) or even
      months (Epstein-Barr-Virus related lymphoproliferative disease) after therapy as
      well as the good long-term effects on graft function suggest long-lasting
      immunosuppressive effects. Since peripheral T-cells reappear in the circulation
      already during therapy (with modulated CD3/T-cell receptor complex) and T-cell
      counts reach commonly pretreatment levels within 2-3 days after cessation of OKT3
      mAb, the long-lasting immunosuppressive effects are not simply explainable by T
      cell depletion. We wondered whether T-cells reappearing in the circulation after
      cessation of therapy, were functionally different from those before OKT3 mAb
      therapy. Our data suggest a selective depletion of activated T-cells particularly
      of type 1-like T-cells by OKT3 mAb resulting in long-lasting immune deviation
      that may explain the long-term effects of OKT3 mAb treatment.

PMID- 9232444
TI  - Targeted expression of MHC class II genes to dendritic cells in vivo.

PMID- 9232445
TI  - Fc gamma receptor type IIb induced recruitment of inositol and protein
      phosphatases to the signal transductory complex of human B-cell.
AB  - Co-clustering of Fc gamma RIIb and B-cell receptor (BCR) inhibits cell activation
      by interrupting BCR stimulated signal transduction. The immunoreceptor tyrosine
      based inhibitory motif (ITIM) of Fc gamma RIIb becomes tyrosyl phosphorylated (P
      ITIM) upon co-clustering with BCR then P-ITIM interacts with several signalling
      molecules, some of which negatively regulate the cell activation process. The
      molecules recruited by the P-ITIM of human Fc gamma RIIb have not been
      characterised yet. In order to affinity isolate the potential functional partner
      molecules of human Fc gamma RIIb, synthetic peptides were designed to cover
      almost the entire intracellular Fc gamma RIIb domain, including Fc gamma RIIb2
      specific sequences and stretches containing the phosphorylated and non
      phosphorylated ITIM. We report here that several tyrosyl phosphorylated proteins
      bind to the P-ITIM peptide from both resting and activated B-cell lysates, the 53
      56 kDa being the most prominent one. A fraction of the 53-56 kDa bands were
      identified as the protein tyrosine kinase (PTK), Lyn which also bound to ITIM
      peptide, pointing to its role in initiating Fc gamma RIIb-mediated negative
      regulation. Among the P-ITIM associated tyr phosphorylated components, the 145
      kDa one was identified as the inositol polyphosphate 5-phosphatase, SHIP and the
      72 kDa protein as the protein tyrosine phosphatase (PTP) SHP2, whereas SHP1 was
      not detected. Phosphatase activity assays showed that P-ITIM bound about five
      times higher SHIP and four times higher PTP activity than the ITIM containing
      peptide. Furthermore, we detected PKC and MAPK in both ITIM and P-ITIM peptides
      precipitated samples. Since human B-cells express both Fc gamma RIIb1 and Fc
      gamma RIIb2, differing in a 19 amino acid insert in the cytoplasmic tail of the
      former, we investigated the components binding to Fc gamma RIIb1 and Fc gamma
      RIIb2 specific sequences. Synthetic peptide representing Fc gamma RIIb1 and Fc
      gamma RIIb2 specific sequences weakly bound unidentified tyr phosphorylated
      proteins at 50-56 kDa, while the insert itself did not bind a detectable amount
      of protein. Neither of the ITIM or P-ITIM bound molecules were observed in
      samples precipitated with peptides corresponding to Fc gamma RIIb1 or Fc gamma
      RIIb2 specific sequences. These observations suggest that protein kinases
      associate with both ITIM and P-ITIM of human Fc gamma RIIb, Lyn being responsible
      for the tyrosyl phosphorylation of ITIM. SHIP and SHP2 phosphatases selectively
      bind to the phosphorylated ITIM. Based on these data we assume that SHIP and SHP2
      recruited in vivo to the Fc gamma RIIb co-clustered BCR are responsible for the
      Fc gamma RIIb mediated negative regulation of human B-cell activation.

PMID- 9232446
TI  - Molecular analysis of the fyn-complex: cloning of SKAP55 and SLAP-130, two novel
      adaptor proteins which associate with fyn and may participate in the regulation
      of T cell receptor-mediated signaling.

PMID- 9232447
TI  - NF-ATp plays a prominent role in the transcriptional induction of Th2-type
      lymphokines.

PMID- 9232448
TI  - Allergen induced cytokine profiles in type I allergic individuals before and
      after immunotherapy.
AB  - Allergen immunotherapy (IT) involves subcutaneous injections of increasing doses
      of specific allergen over a period of time. It is recognised as highly effective
      in the treatment of patients with allergic rhinitis. However, the specific
      immunological mechanisms by which IT achieves its effect have not been fully
      elucidated. Recent studies, have shown that the clinical effects following IT of
      allergic individuals is concomitant with a reduced production of IL-4 by allergen
      specific CD4+ T-cells. The aim of the present study was to gain better knowledge
      about the immunological mechanisms by which IT exerts its beneficial effects. For
      this purpose, peripheral blood mononuclear cells (PBMC) from ten individuals
      receiving birch allergen or placebo in an IT-study performed in a double-blind
      manner, were analysed for IL-4, IFN-gamma, IL-5 and IL-10 mRNA expression at the
      onset of the study and during the pollen season, during treatment. Both
      spontaneous and in vitro allergen-induced cytokine mRNA expression was analysed
      using reverse transcriptase-polymerase chain reaction (RT-PCR). Spontaneous
      expression of IL-4 mRNA could be detected in most of the allergic patients, but
      not in healthy donors. The IT-treated patients showed a decrease in the
      spontaneous expression of IL-4 mRNA during the pollen season as compared to at
      the onset of the study, while in patients receiving placebo the IL-4 mRNA
      expression increased or remained unchanged. Similar results were obtained after
      in vitro stimulation with allergen. This was in contrast to the results for IFN
      gamma, which was readily detected in both patient groups with no significant
      differences between the groups at either timepoint. IL-5 was shown to be
      increased during the pollen season in both groups and thereby presumably not
      affected by allergen IT. Taken together, these observations suggest that the
      cytokine profiles in circulating T lymphocytes change as a consequence of
      allergen IT.

PMID- 9232449
TI  - A case of primary immunodeficiency due to a defect of the major
      histocompatibility gene complex class I processing and presentation pathway.
AB  - INTRODUCTION: We report a case of primary immunodeficiency due to a defect of the
      TAP transporter, an heterodimeric complex which controls the expression of HLA
      class I molecule by delivering peptides from the cytosol into the lumen of the
      endoplasmic reticulum. Since childhood, the 36 year old female suffered from
      recurrent sinusitis/bronchitis. She later developed bronchiectasis and
      destructive nasal epitheloid granulomata in conjunction with a generalized
      vasculitic syndrome that did not improve upon immunosuppression and antibiotics.
      METHODS: The class I monomorphic W6/32 was used for cell surface staining and
      immunoprecipitation of MHC class I molecules. Peptide transport assay was carried
      out in semi-permeabilized cells with iodinated peptides. Antigen presentation
      experiments were performed using chromium 51 labelled patient B cell line and EBV
      specific CTL. TAP1 and TAP2 specific antibodies were used for Western blotting
      and immunoprecipitation of the TAP complex. RESULTS AND CONCLUSIONS: A severe
      reduction of MHC class I molecules at the cell surface of the B-cell lines was
      observed, whereas MHC class II expression was not altered. Isoelectric focusing
      of metabolically labelled MHC class I molecules revealed that class I heavy
      chains remain unsialylated, consistent with a block of TAP dependent peptide
      translocation. These conclusions were confirmed by further experiments showing
      that peptide translocation was completely abolished. We also demonstrated that
      presentation of viral antigens through endogenous class I molecules was severely
      impaired. Immunoprecipitation and Western blotting of TAP1/2 complex showed that
      TAP2 was not detectable. Further, experiments are in progress to identify the
      site of the mutation.

PMID- 9232450
TI  - CD45RA-expressing memory/effector Th cells committed to production of interferon
      gamma lack expression of CD31.
AB  - It has been considered before that human naive and memory/effector CD4+ T-cells
      cannot be subdivided solely according to the differential expression of CD45
      isoforms. By the lack of expression of CD31 we have identified a subset of CD4+
      CD45RA+ CD31- cells which show distinct features of antigen-experienced Th1
      cells. Short term stimulation of highly purified human peripheral blood CD4+ T
      cells with PMA/ionomycin, followed by the cytometric analysis of intracellular
      cytokines, showed that a minor subpopulation of CD4+ CD45RA+ CD45RO- cells is
      able to produce interferon-gamma (IFN-gamma) rapidly, a characteristic of antigen
      experienced Th1 cells. Whereas among CD45RA+ CD4+ T-cells both CD31+ and CD31-
      subsets produce interleukin-2 (IL-2) upon PMA/ionomycin stimulation, only the
      CD31- subpopulation is able to produce IFN-gamma. Thus, our phenotypic and
      functional characterization of CD45RA+ CD45RO- Th cells shows that CD45RA+ CD45RO
      cells do not represent a homogeneous population of antigen-unexperienced, naive
      T-cells. We speculate that a certain subset of human CD4+, CD45RO+ memory T-cells
      reverts to expression of the CD45RA isoform, and that this subset can be
      identified by the lack of CD31 expression.

PMID- 9232452
TI  - Macrophage scavenger receptor MARCO: in vitro and in vivo regulation and
      involvement in the anti-bacterial host defense.

PMID- 9232451
TI  - Molecular mimicry as a therapeutic approach for an autoimmune disease: oral
      treatment of uveitis-patients with an MHC-peptide crossreactive with autoantigen-
      first results.
AB  - In the rat model of experimental autoimmune uveitis (EAU) we have demonstrated
      that a peptide from the sequence of human disease-associated MHC-class I antigens
      can induce uveitis upon immunization. Moreover, oral administration of this MHC
      peptide tolerized Lewis rats to the disease induced with two different retinal
      autoantigens, retinal S-antigen (S-Ag) and IRBP. In uveitis patients T cells
      responding to S-Ag peptide also respond to the MHC-peptide, which shows
      crossreactivity with the major epitope from S-Ag due to some shared discontinuous
      amino acid homologies. The 14-mer peptide B27PD is derived from the sequence of
      all HLA-B antigens that are statistically associated with uveitis (including HLA
      B27). Patients with long-lasting endogenous uveitis, suffering from side effects
      of conventional immuno-suppressive therapy or being therapy-refractive, were
      orally tolerized with peptide B27PD in this first open therapeutic trial.
      Patients received peptide three times a week over a 12 weeks period, while only
      low dose steroids were allowed as concomitant medication. The aims were (1) to
      investigate whether immunosuppressive therapy could be discontinued and steroids
      reduced while relapses of ocular inflammation reside and (2) to search for side
      effects. The Helsinki Declaration was strictly observed and the study design
      approved by the local ethical committee. The first patients orally tolerized with
      the HLA-peptide (two had stopped azathioprine immediately prior to onset of oral
      peptide treatment) could discontinue their steroids because of reduced
      intraocular inflammation. No side effects of therapy were observed. Oral
      tolerance induction with a peptide derived from the patients' own HLA-antigens
      and crossreactive with the organ-specific autoantigen seems to be a potent
      therapeutic approach.

PMID- 9232453
TI  - HLA-DM stabilizes empty HLA-DR molecules in a chaperone-like fashion.
AB  - HLA-DM (DM) is a non-classical major histocompatibility complex (MHC) class II
      molecule that interacts with classical MHC II molecules in acidic compartments.
      During this association DM is supposed to catalyze the release of invariant chain
      (II)-derived CLIP peptides thereby rendering the peptide binding groove
      accessible for antigenic peptide loading. However, in situations of peptide
      scarcity the fate of these DM:DR complexes is not known. We could show that DR
      molecules incubated at lysosomal pH in the absence of peptide rapidly undergo
      functional inactivation and aggregation. In the presence of DM, however, empty DR
      molecules were shown to be stabilised and kept receptive for peptide loading,
      with the degree of the stabilising effect of DM varying for different DR alleles.
      In addition, in lysosomal compartments a considerable fraction of DM was found to
      be stably associated with empty DR alpha beta dimers thereby preserving their
      functionality. Upon encounter with antigenic peptide the DM-associated DR
      molecules could be rapidly loaded, whereupon they did no longer bind to DM. Thus,
      DM seems to act as a dedicated class II-specific chaperone that rescues uncharged
      alpha beta dimers. In view of the suggested shortage of self-peptides in the
      loading compartment, empty class II molecules that are kept receptive for loading
      by the chaperone function of DM may enable the antigen processing system to
      respond promptly to the challenge by newly entering antigens.

PMID- 9232454
TI  - Cytomegaloviruses use multiple mechanisms to elude the host immune response.
AB  - The study of the effects of cytomegaloviruses on the MHC class I-restricted
      antigen presentation pathway has yielded an embarrassment of riches. The human
      cytomegalovirus (HCMV) encodes at least five to six different glycoproteins, each
      interfering in a different way with elimination of the virus by the host immune
      system. Most likely, it is the concerted action of these glycoproteins that
      allows HCMV to escape from elimination by the host immune system during acute and
      perhaps also persistent infection. Prime targets of these CMV glycoproteins are
      MHC class I glycoproteins: the very molecules that signal the presence of a
      virally infected cell to the immune system. Recently, several novel links in the
      multi-step process of immune evasion by HCMV have been discovered.

PMID- 9232455
TI  - Functional activity of murine CD44 variant isoforms in allergic and delayed type
      hypersensitivity.
AB  - There is ample evidence that the family of CD44 glycoproteins is involved in
      homing, maturation and activation of lymphocytes. Furthermore, recent evidence
      suggests that CD44 splice variants are particularly involved in the process of
      lymphocyte activation whereby it was hypothesized that different isoforms may
      fulfill distinct functions. We here addressed the question of CD44v6 and CD44v7
      being involved in TH1 and TH2 reactions using as model systems for TH1 activation
      a TNBS-induced colitis and a DNFB-induced DTH reaction and for TH2 activation a
      FITC-induced allergic dermatitis. With the exception of a small subpopulation of
      lymphocytes in Peyer's patches, expression of neither CD44v6 nor CD44v7 was noted
      in the absence of an antigenic stimulus. Both CD44 variant exons are transiently
      detected on T lymphocytes during mounting of an immune response. In vitro studies
      revealed that antibodies against both CD44v6 and CD44v7 inhibited lymphocyte
      proliferation and cytokine production. Based on these findings the efficiency of
      anti-CD44v6 and anti-CD44v7 treatment was evaluated in vivo in TH1 and TH2
      dependent autoimmune and DTH reactions. Anti-CD44v7 completely abrogated
      development of a death promoting colitis and anti-CD44v6 as well as anti-CD44v7
      significantly mitigated the DNFB-induced, TH1-mediated DTH reactions, while only
      anti-CD44v7 interfered with a FITC-induced, TH2-mediated allergic contact
      dermatitis. The in vitro analysis of cytokine producing cells supported the
      assumption. In conclusion, it could be demonstrated that CD44v6 and CD44v7 are
      differentially involved in TH1 and TH2 activation and, most importantly, a TH1
      mediated autoimmune disease could be prevented by local application of anti
      CD44v7.

PMID- 9232456
TI  - Economic evaluations and interventions for children and adolescents with mental
      health problems.
AB  - Economic evaluations of interventions for children and adolescents with mental
      health problems are comparatively rare, although the growing need for them is now
      quite widely recognized. This review paper first explains how demands for such
      evaluations have built up, and for what reasons, and then considers the response
      from evaluators. The various modes of economic evaluation are introduced and
      illustrated. Previous and current research is discussed by reference to five
      generic research questions commonly addressed in the wider health economics
      field: What treatment should be provided? When? Where? To whom? How? The review
      concludes with recommendations as to how economic evaluations should be taken
      forward in this increasingly important area of intervention.

PMID- 9232457
TI  - Cognitive neuropsychology and its application to children.
AB  - Cognitive neuropsychology has been used successfully in the analysis of adult
      neuropsychological disorders in both verbal and nonverbal domains. When applied
      to children, it aims to construct models on the basis of functional lesions
      manifest within developing systems and provides a theoretical framework within
      which patterns of intact and deficient skills can be charted over time. These
      patterns constrain possible underlying models. In highlighting potential
      individual differences in the acquisition of skills and indicating intact skills
      within subjects, cognitive neuropsychology may also enable a precise description
      of the locus of difficulty and potential circumventory routes for remediation
      around it. The theoretical assumptions of cognitive neuropsychology and issues
      relevant to its methodology are discussed, including the terminology and
      principles of modularity, the significance of individual differences and the use
      of case studies, the dynamics of developing systems, current views on plasticity,
      and distinctions between developmental and acquired disorders. The application of
      cognitive neuropsychology to children is discussed in relation to three cognitive
      areas: face recognition disorders, language disorders and arithmetical disorders.
      These illustrate the similarities that there are between many developmental
      cognitive neuropsychological disorders and those seen in adults following brain
      injury. Models derived from studies of adults are helpful in enabling
      understanding of both face recognition disorders and arithmetical disorders in
      childhood. Within language systems, a variety of different types of disorder are
      evident, which not only relate to receptive and productive difficulties but
      differentially affect the core components of the language system. All of the
      disorders discussed illustrate the limitations of functional plasticity in
      development. In each case, there is not a generalised deficit resulting from
      degradation of capabilities independent of task requirements. Rather, there are
      focal and selective disorders which affect subcomponents of cognitive systems. In
      some cases, genetic factors may constrain compensatory mechanisms.

PMID- 9232458
TI  - Connectionism and developmental psychology.
AB  - What features of brain processing and neural development support linguistic and
      cognitive development in young children? To what extent are the profile and
      timing of development in young children determined by a preordained genetic
      programme? Does the environment play a crucial role in determining the patterns
      of change observed in children growing up? These questions have been of central
      concern to developmental psychologists for well over a century. Yet none of them
      have received answers that are generally accepted by the profession. This article
      reviews some recent computational modelling of developmental change in children
      that promises to contribute to a deeper understanding of the issues behind these
      questions. The modelling work exploits artificial neural networks that mimic some
      of the basic properties of neural processing in the brain. These networks involve
      densely connected webs of simple processing units that propagate and transform
      complex patterns of activity. When exposed to a training environment, they
      undergo a process of self-organisation, yielding information processing systems
      that support new forms of behaviour. The study of the dynamics of these systems
      and their learning capabilities promises to provide us with important clues as to
      the nature of the mechanisms underlying development in infants and young
      children.

PMID- 9232460
TI  - Psychiatric aspects of hearing impairments.
AB  - Hearing impairment is a multifaceted condition with medical, social and cultural
      aspects. Children with hearing impairments follow many different developmental
      pathways, some growing up to join the Deaf community. Children with fluctuating
      hearing impairments are at greater risk of behavioural problems and language and
      reading delay. Children with permanent hearing impairment experience the same
      range of mental health problems as hearing children but their presentation,
      treatment and outcome can differ because of differences in communication and
      language use.

PMID- 9232459
TI  - Psychopathology in infancy.
AB  - The first three years of life present unique challenges to the study of
      psychopathology. We highlight four of the issues in a selective review of the
      developmental psychopathology of early childhood, including lack of specificity
      of risk and outcome variables, measurement difficulties, rapid developmental
      changes and the centrality of the relationship context in early childhood. We
      also highlight issues relevant to conceptualizations of disorders of infancy,
      emphasizing especially the need for efforts to validate clinical disorders. We
      consider two major domains of infant development that we believe are especially
      relevant to a discussion of psychopathology, namely, regulation of emotion and
      infant-caregiver attachment. Discussions of these two domains of infant
      development and their psychopathological extremes allow us to consider
      conceptualizations of psychopathology from the dual perspectives of developmental
      psychopathology and clinical disorders. We conclude by suggesting a number of
      strategies to build upon previous research.

PMID- 9232461
TI  - Pathogenesis of Tourette's syndrome.
AB  - This review presents a models of disease pathogenesis in the context of CNS
      development. It begins with an exploration of the clinical features and natural
      history of Tourette's syndrome. This is followed by a consideration of the role
      of genetic and nongenetic factors. An effort is then made to review the
      anatomical organization of the basal ganglia and related cortical sites. These
      circuits are intimately involved in the normal processing of sensorimotor,
      cognitive, and emotionally laden information. Evidence implicating these circuits
      in the pathobiology of Tourette's syndrome is then considered. The review closes
      with the prospects for advances in interdisciplinary research and therapeutics
      using this model as a guide.

PMID- 9232462
TI  - Transracial family placements.

PMID- 9232463
TI  - Practitioner review: psychosocial treatments for conduct disorder in children.
AB  - The present paper reviews promising treatments for conduct disorder among
      children and adolescents. The treatments include problem-solving skills training,
      parent management training, functional family therapy and multisystemic therapy.
      For each treatment, conceptual underpinnings, characteristics and outcome
      evidence are highlighted. Limitations associated with these treatments (e.g.
      paucity of long-term follow-up evidence and of evidence for the clinical
      significance of the change) are also presented. Broader issues that affect
      treatment and clinical work with conduct-disordered youths are also addressed,
      including retaining cases in treatment, what treatments do not work, who responds
      well to treatment, comorbidity, the use of combined treatments and the need for
      new models of treatment delivery.

PMID- 9232464
TI  - Infants of depressed mothers exhibit atypical frontal brain activity: a
      replication and extension of previous findings.
AB  - The left frontal brain region is specialized for expression of positive emotions
      (e.g. joy) whereas the right frontal region is specialized for negative emotions
      (e.g. sadness). Depressed adults have been found to exhibit reduced left frontal
      electroencephalographic activity. In this study, baseline frontal and parietal
      EEG activity was measured in 13-15-month-old infants of depressed and
      nondepressed mothers who were of middle income with no other major psychiatric
      problems. Compared to infants of nondepressed mothers, infants of depressed
      mothers exhibited reduced left frontal EEG activity. Infants of mothers with
      major depression exhibited lower levels of left frontal EEG activity than those
      of mothers with subthreshold depression.

PMID- 9232465
TI  - The impact of paternal alcoholism and maternal social position on boys' school
      adjustment, pubertal maturation and sexual behavior: a test of two competing
      hypotheses.
AB  - Two competing hypotheses concerning the effects of stressful environments on the
      onset of puberty were tested using longitudinal data for a sample of boys from
      low socioeconomic backgrounds. Paternal alcoholism and maternal social position
      were used as indicators of family stress. School placement was monitored from
      school entry to 14 years of age. Teachers rated the boys' disruptive and anxious
      behaviors, while the boys reported on parenting behaviors at 10 years of age.
      Pubertal maturation, age of first sexual intercourse and sexual behavior were
      assessed between 11 and 14 years of age. The prepubertal data indicated that boys
      with an alcoholic father, or a mother from a low social position, were more
      stressed and had more behavior problems: the boys with alcoholic fathers
      perceived their parents as being more punitive, and as setting fewer rules
      concerning their behavior; those who had at least one maladjusted parent were
      more often placed out of an age-appropriate regular classroom, and were rated
      more disruptive and more anxious by their teachers. Paradoxically, the results
      for the onset of puberty gave support to the two rival hypotheses. Paternal
      alcoholism led to a delay of male pubertal onset, as suggested by the hypothesis
      that stress activates the hypothalamic-pituitary-adrenal axis, and inhibits the
      hypothalamic-pituitary-gonadal axis. However, sons of alcoholic fathers had more
      frequent sexual intercourse and more sexual partners, as suggested by the
      evolutionary theory of socialization. High maternal social position acted as a
      protective factor for school placement of boys with an alcoholic father. These
      results challenged a key hypothesis of the evolutionary theory of socialization
      for males. They indicated that the link between childhood family environment,
      behavior development, pubertal maturation and sexual promiscuity are more complex
      than anticipated.

PMID- 9232466
TI  - The effects of neonatal jaundice and respiratory complications on learning and
      habituation in 5- to 11-month-old infants.
AB  - The influences of neonatal hyperbilirubinemia and respiratory complications were
      examined in 5- to 11-month-old infants in two studies. One study focused on
      habituation performance and the other on contingency learning. In both
      experiments, three neonatal jaundice conditions (no jaundice history, measured
      bilirubin, phototherapy) were crossed with two levels of neonatal respiratory
      risk (no oxygen intervention, oxygen intervention). For low respiratory risk
      subjects there were increasingly adverse effects for both habituation and
      learning the more severe the jaundice history. A complex pattern emerged for the
      high respiratory risk groups. Only for the learning task were the results
      consistent with a summative effect of neonatal jaundice and respiratory risk
      factors.

PMID- 9232467
TI  - Asperger syndrome, autism and attention disorders: a comparative study of the
      cognitive profiles of 120 children.
AB  - The Wechsler Intelligence Scale for Children-Revised (WISC-R) was applied (in a
      Swedish version) in 120 children with Asperger syndrome, autistic disorder, and
      attention disorders. Using stepwise logistic regression analysis, the WISC's
      discriminating ability was investigated. The overall rate of correct diagnostic
      classification was 63%. Further, WISC profiles were analysed within each group.
      The group with autistic disorder was characterised by a peak on Block Design. The
      Asperger syndrome group had good verbal ability and troughs on Object Assembly
      and Coding. The group with attention disorders had troughs on Coding and
      Arithmetic. The results suggest that Kaufman's Verbal Comprehension, Perceptual
      Organisation and Freedom from Distractibility factors rather than verbal IQ and
      performance IQ account for the variance on the WISC. Furthermore, the Asperger
      syndrome and autistic disorder groups differed in respect of "fluid" and
      "crystallised" cognitive ability.

PMID- 9232468
TI  - The identification of pervasive hyperactivity: is clinic observation necessary?
AB  - Three groups of hyperactive children (clinic observed, reported and situational)
      and a normal control group were compared on measures of behavioural,
      developmental and cognitive functioning. The clinic observed and reported groups
      did not differ significantly on any of the dependent variables. Situationally
      hyperactive children were less active, and had fewer behavioural and social
      difficulties than children with pervasive hyperactivity. Normal control subjects
      were distinguished by their better academic and social performance, and the
      absence of behaviour problems, language delay and hearing concerns. The data
      support the distinction between pervasive and situational hyperactivity, but not
      the separation of pervasive hyperactivity into clinic observable and reported
      hyperactivity.

PMID- 9232469
TI  - Do children need concurrent prompts in order to use lexical analogies in reading?
AB  - In two experiments, children were taught a word and then given reminders of that
      word while reading unfamiliar analogous words. Reminders of the pronunciation of
      taught words facilitated reading of rime analogous words (e.g. beak-peak) over
      head analogous words (e.g. beak-bean) in Experiment 1, and onset analogous words
      (e.g. stilt-stem), over medial analogous words (e.g. stilt-milk) in Experiment 2.
      Importantly, however, privileged improvement for rime and onset analogous words
      was not evident in the absence of these concurrent prompts. The findings suggest
      that the analogy model developed by Goswami (1993) may have limited applicability
      in naturalistic settings.

PMID- 9232470
TI  - Did Asperger's cases have Asperger disorder? A research note.
AB  - With publication of the fourth edition of the Diagnostic and statistical manual
      of mental disorders (DSM-IV), standardized criteria for Asperger Disorder, a
      putative subtype of Pervasive Developmental Disorder, are now available. This
      paper examines the four cases Asperger originally presented in his seminal paper
      (1991/1994), using DSM-IV criteria to determine whether a diagnosis of Autistic
      or Asperger Disorder is most appropriate. We found that all four cases met DSM-IV
      criteria for Autistic Disorder, rather than Asperger Disorder. This suggests that
      the syndrome Asperger originally described may not be captured by present
      diagnostic criteria. Implications for future research are discussed.

PMID- 9232471
TI  - A new instrument to assess sibling relationships in antisocial youth: the social
      interaction between siblings (SIBS) interview: a research note.
AB  - This paper presents psychometric information on a new interview (SIBS) designed
      to examine sibling influences on antisocial behavior. The feasibility of the
      instrument and internal consistency of the SIBS scales was documented in a sample
      of 29 children (ages 6-11) with a delinquent older brother. In addition, adequate
      to excellent test-retest reliability of the SIBS scales was demonstrated in an
      unselected sample. The potential utility of the SIBS interview for assessing the
      role of siblings in the development of antisocial behavior is discussed.

PMID- 9232472
TI  - Selective mutism: a population-based study: a research note.
AB  - Seven-year-olds to 15-year-olds in 2 school districts of Goteborg, Sweden, were
      screened for selective mutism by their teachers and follow-up was achieved for a
      full school year. Three girls and 2 boys met DSM-IV criteria for selective mutism
      and a further 25 had a combination of shyness and reticence that did not amount
      to clinical disorder. The rate of typical selective mutism was 18 in 10,000
      children. Shyness/reticence occurred in 89 in 10,000 children. Selective mutism
      was more common than suggested by earlier studies. Teachers of school age
      children need to be better informed about its existence.

PMID- 9232473
TI  - Outcome of anorexia nervosa in the younger patient.

PMID- 9232474
TI  - The aftercare of adolescents with deliberate self-harm.
AB  - The evaluation and aftercare of the adolescent suicide attempter is described.
      The assessment of suicidal risk is aimed at the identification of those factors
      present in the patient and environment that make repetition of suicidal behavior
      likely. These factors, along with the motivation and precipitant for the suicide
      attempt, are used to determine the intensity of care and targets of treatment.
      Important elements of treatment include: obtaining a no-suicide contract,
      addressing potential sources of noncompliance, determining proper intensity of
      treatment, provision of family psychoeducation addressing ongoing family
      difficulties, treatment of co-occurring psychopathology, and remediation of
      social skills and problem-solving deficits.

PMID- 9232475
TI  - The Emanuel Miller Memorial Lecture 1994. Depressive disorders in childhood: an
      impressionistic landscape.
AB  - To convey an impressionistic landscape of depressive disorders in childhood,
      studies of clinically referred and diagnosed patients as well as community
      samples, and data from experimental investigations are used to consider five
      questions: Are depressive syndromes morbid states in childhood? Should we be
      concerned about depression in childhood? How do very early-onset depressions
      arise? What happens to depressed children as they grow up? And how can we help
      youngsters who suffer from depression? The information is discussed with respect
      to its implications for the management of clinically depressed children, as well
      as the prevention of very early-onset depressive disorders.

PMID- 9232476
TI  - Adolescent dieting: healthy weight control or borderline eating disorder?
AB  - Dieting in adolescent girls is ubiquitous but its health significance is
      uncertain. On the one hand it might be seen as promoting healthy weight control
      and on the other it might be considered as a risk factor for eating disorders.
      Dieting levels were systematically assessed in a representative group of 2525
      Australian teenagers and classified using item response theory. In this group,
      38% of girls and 12% of boys were categorised as intermediate dieters; 7% of
      girls and 1% of boys fell into a group of extreme dieters. Body mass carried a
      strong positive association with intermediate dieting. Most female dieters,
      nevertheless, fell within a normal weight range. Psychiatric morbidity was the
      clearest factor associated with extreme dieting and 62% of extreme dieters
      reported high levels of depression and anxiety. Extreme dieting might reasonably
      be viewed as lying on a spectrum with clinical eating disorders. Most dieting is
      unjustified on the grounds of appropriate weight control and appears to reflect a
      widespread striving of teenage girls towards body shapes at the lower end of age
      adjusted norms.

PMID- 9232477
TI  - Mothers' representations of their infants assessed prenatally: stability and
      association with infants' attachment classifications.
AB  - The stability and predictive validity of classifications of mothers'
      representations of their infants as determined by the Working Model of the Child
      Interview (WMCI) were examined. Concordance between mothers' representations of
      their infants assessed prenatally and again one year later and infant Strange
      Situation (SS) attachment classifications at 12 months was also examined. WMCI
      classifications were stable over 12 months in 80% of mothers, compared to 51%
      expected by chance alone. Pregnancy WMCIs predicted infant SS classifications in
      74% of cases, compared to 54% expected by chance. Concordance between 11-month
      WMCI and 12-months SS classifications was 73% (vs. 55% expected by chance).
      Problems with the skewed distribution of the sample, the low concordance between
      pregnancy and 11 months for one of the three classifications, and future
      directions for research are discussed.

PMID- 9232478
TI  - Behavioural adjustment in school of very low birthweight children.
AB  - The school-based behavioural adjustment at 7-8 years of a cohort of 243
      prematurely born, very low birthweight (< 1501 g) children and their normal
      birthweight controls is reported. The findings indicate that the children born
      preterm (both male and female) were rated by their teachers as expressing more
      behaviour problems than their controls, and were less well adjusted to the school
      environment. The deficits noted in the preterms applied across the social
      classes, with no amelioration noted in preterms of higher social class. It is
      speculated that the problem behaviours reflect a failure in self-regulatory
      functions.

PMID- 9232479
TI  - Children with a pervasive developmental disorder, children with a language
      disorder and normally developing children in situations with high- and low-level
      involvement of the caregiver.
AB  - The social behaviour of low-functioning children with a Pervasive Development
      Disorder (PDD), high-functioning children with a PDD, children with a Language
      Disorder (LD) and normally developing children (ND) was investigated in a
      playroom session while they were interacting with one of their parents. High
      functioning children with a PDD were found to differ from the other groups in
      social responsivity. Low-functioning children with a PDD differed from high
      functioning children with a PDD in the total number of social bids, type of
      social bids, number of looks at parent and social responsivity. When parents
      structured the behaviour of their children, this resulted in an increase in
      number of social bids and looks in the low-functioning children with PDD.

PMID- 9232480
TI  - Autism and the immune system.
AB  - As our knowledge of the interactions of the immune, nervous and endocrine systems
      progresses, complex links with the origin and course of psychopathology in
      childhood are revealed. In this article the neuroimmunological literature on
      autism is reviewed. Relevant aspects of immune functioning and the neuroendocrine
      immune network are described. We present the immunological findings in autistic
      patients within two related conceptual frameworks: a viral and an autoimmune
      hypothesis. Interpretation of data is hampered by conceptual and methodological
      differences between studies. Both the clinical significance of the immune changes
      and the causal connection between immune changes and psychopathological phenomena
      in autism remain to be elucidated. Recommendations for further research are
      given.

PMID- 9232481
TI  - How specific are "specific developmental disorders"? The relevance of the concept
      of specific developmental disorders for the classification of childhood
      developmental disorders.
AB  - The concept of "specific developmental disorder" (SDD) refers to delays in
      developmental domains such as language and speech development, motor coordination
      or the development of scholastic skills, in the absence of sensory deficits,
      subnormal intelligence or poor educational conditions. The key element in this
      concept is the notion of a discrepancy between observed and expected level of
      development. In DSM-III-R and ICD-10, SDD serves as a conceptual umbrella,
      suggesting that the subsumed disorders are of the same type. In DSM-IV, the SDD
      umbrella is not used explicitly, but the notion of a discrepancy is present in
      the categories of Learning Disorders, Motor Skill Disorder and Communication
      Disorders, suggesting a close relationship between these disorders. One of the
      advantages of the use of SDD as a unifying concept is that it contributes to the
      standardisation of the description of the various disorders. However, based on
      reviews of research regarding the reliability and validity of the SDD categories,
      we argue that the application of a unifying SDD concept has been premature. For
      each of the categories for disorders in scholastic skills, language, speech and
      motor coordination, the notion of a discrepancy between observed and expected
      level of development should be elaborated and tested more thoroughly, before SDD
      can be used as a unifying concept in classification.

PMID- 9232482
TI  - Memories of childhood neglect and abuse: corroboration in a series of sisters.
AB  - Reports from 87 community-based sister-pairs, selected for high rates of neglect
      or abuse in childhood, have been used to establish validity of the CECA, a
      retrospective interview measure of childhood experience. Corroboration was based
      on independent assessments of sisters' accounts of what happened to each other in
      childhood. Corroboration of scales assessing parental neglect, physical abuse in
      the household and sexual abuse (either household or nonhousehold) was
      satisfactory, with a mean correlation for the three experiences of .60 (weighted
      kappa [Kw]). Concordance reflected the degree to which experience was shared and
      was judged by comparing the sisters' accounts of their own experience. Among
      sisters with shared (concordant) experience for neglect or abuse, corroboration
      was high (mean of .74), but for those with nonshared (nonconcordant) experience
      it was largely absent (mean of .01). The degree to which the experiences of
      neglect or abuse were concordant was related to whether the perpetrator was a
      member of the household. Neglect and physical abuse were by definition from
      household members (mainly parents) and involved high concordance of experience.
      Sexual abuse occurred from many sources and in practice was commonly from an
      adult living outside the household and such experiences were less likely to be
      shared by sisters. An overall index indicating the presence of at least one
      abusive experience before the age of 17 showed a concordance of .64 with
      corroboration between sisters as high as .70. Issues involving retrospective
      recall and measurement are discussed.

PMID- 9232483
TI  - Psychogenic disorders of vision in childhood ("visual conversion reactions"):
      perspectives from adolescence: a research note.
AB  - Fifteen adolescents who had exhibited psychogenic disorders of vision in
      childhood were compared with a control group of adolescents who had experienced
      childhood visual dysfunction of organic origin. The principal modes of assessment
      were clinical interviews, the Parental Bonding Instrument (PBI), and self-report
      measures concerning specific personality traits. Adolescents who had previously
      presented with psychogenic disorder were more likely to (1) report having
      experienced school difficulties and the loss of a significant figure at the time
      of presentation, (2) rate their mothers as over-involved on the PBI and (3)
      report adjustment difficulties and obsessional personality traits in adolescence.

PMID- 9232484
TI  - Treatment of childhood Phobias.

PMID- 9232485
TI  - Parent-reported problems in 211 adopted children: some risk and protective
      factors.
AB  - Parents of 211 adopted children, now young adults, were interviewed about their
      children's behaviour and development during childhood and adolescence. The
      children were placed for adoption at different ages. The quality of children's
      pre-placement care also varied, older-placed children generally experiencing
      adverse backgrounds prior to joining their adoptive parents. Depending on their
      quality of pre-placement care, the children were placed in one of three groups
      for the purposes of analysis: (a) baby adoptions, (b) older-children adoptions in
      which children had enjoyed satisfactory care as babies, and (c) older-children
      adoptions in which children had experienced adverse care as babies. The rate of
      adolescent problem behaviours varied between the three groups, with the older
      children adoptions/adverse baby care group showing the highest rates. Two
      subgroups were identified. A quarter of the baby-adopted children were reported
      to have had problem behaviours during adolescence. In contrast, no problem
      behaviours were reported in 28% of the older-adopted/adverse baby care children.
      Some possible risk and protective factors are explored.

PMID- 9232486
TI  - Subclinical hallucinations and delusions in nonpsychotic adolescents.
AB  - A number of studies have suggested that clinical populations of adolescents may
      report hallucinations and/or delusions without meeting criteria for a psychotic
      disorder. The purpose of this study was to provide information about the
      prevalence and symptom correlates of these subclinical hallucinations and
      delusions that occur in a nonpsychotic population of adolescents. Thirty-eight
      adolescents from a residential program and day treatment center were assessed
      with respect to hallucinatory experiences, ideas of reference, paranoid ideation,
      dissociative experiences, depressive symptomatology, and schizotypal cognitions.
      Results of this study indicated that 33% of the participants reported having
      experienced auditory hallucinations, and 24% reported having had delusional
      ideas. In addition, the results suggest that subclinical auditory hallucinations
      may have an especially strong relation with dissociative processes, whereas
      subclinical delusions appeared to be most strongly correlated with schizotypal
      thought processes. The results of this study begin to clarify the phenomenon of
      hallucinatory and delusional experiences in a nonpsychotic population.

PMID- 9232488
TI  - Diagnostic agreement between clinicians and the Diagnostic Interview for Children
      and Adolescents--DICA-R--in an outpatient sample.
AB  - The paper examines the diagnostic agreement between clinicians and the Diagnostic
      Interview for Children and Adolescents. One hundred and thirty-seven outpatients
      children and adolescents, and their parents-were diagnosed independently
      following DSM-III-R criteria by clinicians and by the DICA-R. The diagnostic
      concordance between clinicians and DICA-R ranged from low to moderate in the
      majority of the categories. The only exception was Conduct Disorder. Differences
      depending on the informant and the quality of the information (cognitive vs.
      observable) were observed. Combining the information from the child/adolescent
      and their parents ameliorates the concordance. The reasons for the scanty
      agreement found could be due to the fact that clinicians and structured
      interviews differ in what they evaluate (conditions on which they focus), how
      they evaluate (strictness in the criteria application, use of different
      informants and different information etc.), and when they evaluate (present
      condition vs. lifespan). After analysing the pros and cons of both, the use of
      structured interviews is advisable for research purposes. There is a clear need
      for a variety of informants, and the combination of information from different
      sources is recommended, depending on the age of the children and the type of
      disorder.

PMID- 9232487
TI  - Children with schizophrenia-spectrum disorders: thought disorder and
      communication problems in a family interactional context.
AB  - Thought disorder and communication patterns during an interactional task were
      examined in families of children with schizophrenia-spectrum disorders
      (schizophrenia and schizotypal personality disorder), depressed children, and
      normal controls. Children with schizophrenia-spectrum disorders showed
      significantly more thought disorder than their normal peers; levels of thought
      disorder among depressed children fell between those observed in the other two
      groups but did not differ significantly from either of them. Similarly, mothers
      of children with schizophrenia-spectrum disorders showed more thought disorder
      than mothers of normal control children but did not differ from mothers of
      depressed children. Children with schizotypal personality disorder did not differ
      from children with schizophrenia. These findings demonstrate that the thought
      disorder present in childhood-onset schizophrenia and schizotypal personality
      disorders is manifest in an important social context, the family.

PMID- 9232489
TI  - Effects of age of entry, day-care quality, and family characteristics on
      preschool behavior.
AB  - Teachers evaluated 155 4-5-year-old children attending Montreal day-care centers
      of excellent (N = 51), average (N = 60), or low (N = 44) quality using behavioral
      scales. Age of entry to day-care was also considered. Center quality was assessed
      by two observers using the Early Childhood Environment Rating Scale. Results
      point to the positive effects of longer exposure to high-quality group day-care
      (increased interest-participation), and the negative effects of longer exposure
      to low-quality centers (increased anger-defiance). Positive or negative family
      characteristics contributed further to these effects.

PMID- 9232490
TI  - Kindergarten-aged children's reactions to an emotionally charged naturalistic
      event: relations between cognitions, self-reported emotions, and emotional
      behaviour.
AB  - Relations between kindergarten-aged children's cognitions, self-reported
      emotions, and expressive behaviour regarding an emotion-eliciting event were
      examined by investigating 32 Dutch children's reactions to meeting "Sinterklaas",
      who they think brings presents for children, but who might also punish them.
      Measures included cognitions about Sinterklaas, emotion self-reports, and
      expressive behaviour when meeting Sinterklaas. Girls', but not boys', self
      reports were related to their expressive behaviour. Boys' cognitions were not
      related to their emotions, whereas girls' cognitions and emotions were related
      inversely. That is, girls who reported the most positive cognitions about
      Sinterklaas showed the most, rather than the least, fear.

PMID- 9232491
TI  - Anxiety, antisocial behavior, and heart rate regulation in adolescent males.
AB  - We explored relationships between anxiety and antisocial behavior and autonomic
      heart rate regulation in a homogenous sample (N = 175) of 15-year-old males.
      Measures of anxiety and antisocial behavior were obtained at yearly intervals
      over a period of 4-6 years. Components of heart rate variability associated with
      postural (sympathetic) and respiratory (vagal) change and transfer of respiratory
      to heart rate variability were estimated at age 15 using spectral analytic
      techniques. Anxiety and antisocial behavior were predictably related to enhanced
      and diminished levels of mean heart rate, respectively. Anxiety was also
      predictably related to enhanced sympathetic mediation of phasic postural effects
      on heart rate. Antisocial behavior was unexpectedly related to disruption of
      vagally mediated, phasic respiratory effects on heart rate. Anxiety and
      antisocial behavior showed distinct relationships to heart rate, and to the
      autonomically mediated components of heart rate variability from postural and
      respiratory sources. Spectral analytic techniques helped elucidate these unique
      regulatory patterns, suggesting utility for future research in this area.

PMID- 9232493
TI  - Child and family factors influencing the clinical referral of children with
      hyperactivity: a research note.
AB  - This study examined child and family factors associated with the clinical
      referral of pervasively hyperactive children. Fourteen children with pervasive
      hyperactive behaviour problems referred to a London child guidance service were
      compared with 13 nonreferred pervasively hyperactive children resident in the
      same geographic area. Child behaviour, parenting, and family life factors were
      examined as determinants of referral. Preliminary results suggest that both child
      and parenting factors play an important role in determining whether a child with
      hyperactivity will be referred for child guidance. The best predictors of
      clinical referral were a parent's ability to cope with child behaviour, child
      emotional disturbance, school relationship problems, and parental disciplinary
      indulgence. Implications of referral bias for research and service planning are
      discussed.

PMID- 9232494
TI  - Regnauld procedure in the surgical treatment of metatarsalgia: interpretation of
      follow-up X-ray imaging.
AB  - In lesser ray metatarsalgia (rays 2 through 5) due to an altered Lelievre's
      metatarsal formula (depending on the respective lengths of the metatarsals), the
      resection of metatarsal heads aims at restoring a correct metatarsal support.
      This being a destructive procedure, metatarsal head resection is best indicated
      in the treatment of severe forefoot deformities such as those resulting from
      rheumatoid arthritis. In all metatarsalgias that recognize biomechanical origin,
      the enclavement procedure, according to Regnauld's original report, should be
      preferred. The aim of this study is analysis of the radiographic evolution of the
      metatarsal epiphysis following the Regnauld procedure on the basis of anatomic
      and pathological events occurring during the attachment process. The procedure
      was performed on 31 feet and the patients were followed-up for 24 months
      postoperatively. The enclavement process evolved favorably in all cases. It
      consists of four anatomic/pathologic phases corresponding to typical radiographic
      features. While graft consolidation is achieved in 3 to 4 months postoperatively,
      complete recovery of the metatarsal bony architecture and functional adaptation
      requires 18 to 24 months.

PMID- 9232492
TI  - Early dentine lead levels and educational outcomes at 18 years.
AB  - The associations between early dentine lead levels measured at the age of 6-8
      years and educational outcomes measured at 18 years were examined in a birth
      cohort of 1265 New Zealand children. Analyses showed significant (p < .005)
      dose/response relationships between early dentine lead levels and later outcomes:
      at age 18 children with early elevated lead levels had poorer reading abilities,
      had more often left school early, had more often left school without
      qualifications, and had lower levels of success in school examinations. These
      associations persisted after statistical control for a range of social and
      familial confounding factors. A number of potential threats to the validity of
      the findings are examined, including sample selection bias, statistical
      undercontrol of covariates, and errors of measurement. It is concluded that the
      findings are consistent with the view that early mildly elevated lead levels have
      modest but detectable effects on individual achievement, with these effects
      extending to late adolescence.

PMID- 9232495
TI  - Superficial peroneal nerve entrapment in a young athlete: the diagnostic
      contribution of magnetic resonance imaging.
AB  - Fascial entrapment of the superficial peroneal nerve produced severe pain in the
      ankle and foot of a 16-year-old female athlete after several sprains of the same
      ankle. The pain coexisted with erythema and sensory alteration of the area
      involved. Magnetic resonance imaging confirmed the diagnosis of this unusual
      neuropathy. Limited fasciectomy, at the point where the nerve becomes
      subcutaneous, relieved all symptoms.

PMID- 9232496
TI  - Longitudinal peroneal tendon tears.
AB  - Longitudinal peroneal tendon tears are uncommon. Seven cases are presented: four
      involving peroneus brevis and three of the peroneus longus tendons. Evaluation
      and treatment methods are described along with a diagnostic algorithm. All
      patients noted relief of symptoms with surgical treatment. Magnetic Resonance
      imaging proved useful in aiding diagnosis prior to surgery, revealing a
      hypertrophied peroneal tendon.

PMID- 9232497
TI  - An unclassified fracture of the talus.
AB  - The following is a case report detailing what appears to be a previously
      unreported and unclassified osteochondral fracture of the posterior talar facet.
      This case report will detail the diagnosis and treatment of the fracture, as well
      as provide a brief history of previously reported osteochondral lesions involving
      the talus. The authors suggest a new classification method for these types of
      fractures.

PMID- 9232498
TI  - Navicular body fractures: computerized tomography findings and mechanism of
      injury.
AB  - The case reports of five patients with signs and symptoms of a fracture of the
      tarsal navicular body are presented. Each patient underwent a computerized
      tomography examination to determine the extent of this fracture. Based on the
      computerized tomography findings, surgical or conservative management was carried
      out. The computerized tomography examination, combined with the patient's
      history, has shed new light on a previously undescribed mechanism of injury for
      this fracture.

PMID- 9232500
TI  - The natural history of great toe amputations.
AB  - The purpose of this study is to report the prevalence of reamputation following
      resection of the great toe and first ray in adults with diabetes. We abstracted
      the medical records of 90 diabetic great-toe and first-ray amputees admitted
      between 1981 and 1991. The most common etiologies of initial amputations were
      ulcer with soft tissue infection (39%), ulcer with osteomyelitis (32%), and
      puncture wounds (12%). Sixty percent of all patients had a second amputation, 21%
      had a third, and 7% had a fourth. Fifteen percent of the patients who had a
      second amputation had it contralaterally. Seventeen percent subsequently
      underwent a below-knee amputation and 11% had a Transmetatarsal amputation on the
      same extremity, 3% had a below-knee amputation, and 2% a transmetatarsal
      amputation contralaterally. The mean time from the first to the second amputation
      was approximately 10 months. The results of this study suggest that a large
      proportion of patients undergoing an amputation at the level of the great toe or
      first ray have subsequent amputations in the first year following the initial
      procedure. Additionally, it appears that the contralateral foot may be at
      significant risk for distal amputation following resection of the hallux or first
      day.

PMID- 9232499
TI  - Coralline hydroxyapatite: a bone graft alternative in foot and ankle surgery.
AB  - The use of coralline hydroxyapatite has become a viable bone grafting
      alternative. Its efficacy has been well established through multiple human and
      animal studies. Coralline hydroxyapatite enhances osteogenesis by providing a
      biocompatible lattice for the passage and assembly of vascular, fibroblastic, and
      osteoblastic tissues. It also provides support for surrounding osseous
      structures. The uses of this material are expanding into the realm of foot and
      ankle surgery. Its consideration as an appropriate bone graft substitute as well
      as multiple case studies demonstrating its surgical applicability are discussed.
      The implants utilized at Thorek Hospital and Medical Center over the past eight
      years, with an average follow-up of three and one-half years, have proven to be a
      valuable resource for augmentation where an osseous defect has occurred.

PMID- 9232501
TI  - Technetium-99-labeled leukocytes in diagnosing diabetic osteomyelitis in the
      foot.
AB  - Hexamethylpropylamineoxine (HMPAO)-labeled leukocytes were studied to examine the
      scintigraphic significance of the procedure in diagnosing bone infection in
      patients with chronic nonhealing foot ulcerations. Fifty-two patients were
      scanned with Technetium-99-labeled white blood cells and scintigraphic results
      were compared with histological analysis, bone culture, and radiographic
      findings. Twenty-one patients demonstrated positive uptake with imaging and focal
      accumulation of leukocytes at the area of suspected infection. Sensitivity,
      specificity, and accuracy were calculated and found to be 86%, 90%, and 88%,
      respectively. Thirty-one members of the population were also scanned with Tc-99
      methylene diphosphate (MDP) triphasic scintigraphy. Sensitivity equaled 91% and
      specificity was found to be significantly lower (40%) when compared with the
      leukocyte-labeled scans. Technetium-99 (HMPAO) leukocyte scintigraphs
      demonstrated a significantly higher specificity and accuracy rate when compared
      with Technetium-99 (MDP) triphasic scans.

PMID- 9232502
TI  - Early clinical results of the use of radiofrequency lesioning in the treatment of
      plantar fasciitis.
AB  - In this paper the authors discuss plantar fascial heel pain, including its
      etiology and treatment. The results of a retrospective study using radiofrequency
      lesioning on plantar fascial heel pain are presented and discussed. Thirty-nine
      patients were treated with radiofrequency lesioning, and 92% of the patients
      experienced complete resolution of symptoms following the procedure.

PMID- 9232503
TI  - Bilateral os peroneum fractures: comparison of conservative and surgical
      treatment and outcomes.
AB  - Acute fracture of the os peroneum without concurrent rupture of the peroneus
      longus is a rarely cited injury. Sudden violent contraction of the peroneus
      longus muscle and direct trauma are documented mechanisms of injury. This injury
      can easily be overlooked due to its infrequency, and it may lead to chronic pain
      and impairment of function. Presented is a case of acute fracture of the os
      peroneum bilaterally. The fractures occurred approximately 21 months apart.
      Treatment varied with the right foot responding to 4 months of conservative
      therapy, and the left foot undergoing surgical excision of the fractured ossicle
      following 5 weeks of failed conservative therapy. This case is unique as it
      presents bilateral os peroneum fractures. This unique situation allows for a
      comparison of the two distinct treatment options. A fractured os peroneum without
      peroneus longus tendon rupture may be treated conservatively, however, surgical
      excision of the ossicle following 4 weeks of conservative therapy may expedite
      the recovery period and avoid chronic pain.

PMID- 9232504
TI  - Flexor digitorum accessorius longus muscle: an etiology of tarsal tunnel
      syndrome?
AB  - During routine lower extremity laboratory dissection at the Ohio College of
      Podiatric Medicine, an anomalous muscle, the flexor digitorum accessorius longus
      was uncovered on one male and one female cadaver. The muscles were located in the
      deep posterior compartment of the leg and were of differing sizes and origins.
      This anomalous muscle has been implicated as an etiology for tarsal tunnel
      syndrome. In cases of tarsal tunnel syndrome that undergo surgical decompression,
      the flexor digitorum accessorius longus muscle may be present and may be the
      cause of the tibial nerve compression.

PMID- 9232505
TI  - Subcutaneous phaeohyphomycosis: overview and case report.
AB  - Phaeohyphomycosis describes a heterogenous group of mycotic infections caused by
      pigmented fungi. Previously uncommon to the United States, the number of case
      reports in the American literature has steadily increased over the past two
      decades. This has been attributed to the ever increasing number of
      immunocompromised individuals as well as an influx of immigrants from areas where
      these opportunistic fungi are more commonly found. The authors present a
      generalized overview of phaeohyphomycosis as well as a more specific breakdown
      and case study involving subcutaneous phaeohyphomycosis.

PMID- 9232506
TI  - New procedure for stabilization of lesser metatarsophalangeal joints: a
      preliminary study.
AB  - The article presents initial experience with a novel technique for reduction of
      severely subluxed fifth metatarsophalangeal joints. This involves soft tissue
      realignments, and may be used for other lesser metatarsophalangeal joints. Twelve
      month success is noted on the longest follow-up of 10 procedures performed.

PMID- 9232508
TI  - Children and bioethics: uses and abuses of the best-interests standard.

PMID- 9232507
TI  - Wound management in the diabetic foot.
AB  - The multiple opinions expressed in this Grand Rounds section make it clear that
      management of the diabetic patient with a foot wound is complex at best. Several
      significant points are repeated many times. The need for a detailed history and
      physical exam, accurate assessment of neurologic, vascular, metabolic status, and
      addressing the etiologic factor involved are all essential. All authors point to
      multispecialty integrated treatment protocols to produce the greatest success.
      Little mention is made of the use of topical agents to accelerate healing. This
      is due to the lack of unbiased studies, and the many available reports that
      demonstrate rapid healing when a complete and objective protocol is followed. The
      aims of this Grand Rounds are to stimulate interest in this important subject,
      and to provide the practitioner with a scaffold with which to build their own
      wound care management protocols.

PMID- 9232509
TI  - Parenting and the best interests of minors.
AB  - The treatment decisions of competent adults, especially treatment refusals, are
      generally respected. In the case of minors something turns on their age, and
      older minors ought increasingly to make their own decisions. On the other hand,
      parents decide on behalf of infants and young children. Their right to do so can
      best be justified in terms of the importance of preserving intimate family
      relationships, rather than in terms of the child's best interests, although the
      child's best interests will most often follow from this arrangement.
      Nevertheless, there are and ought to be legal, ethical, and financial constraints
      on parental decision making.

PMID- 9232510
TI  - Genetic testing in children.
AB  - In this article, the author focuses on the allocation of decision-making
      authority between parents and physicians. She argues that parents should have
      substantial room to decide whether genetic testing is good for their child and
      that they may appropriately consider interests in addition to those of their
      child in making such choices. A physician, however, may refuse to act pursuant to
      parental views about testing, when in the physician's view, the parents' choices
      would pose a risk of significant harm to the child. The balance of control
      between parents and physicians is illustrated by discussion of a series of case
      vignettes. Refusal to perform requested testing is most often warranted for
      testing for carrier status and for genetic predisposition to late onset disease.
      The author concludes her analysis by discussing why it is appropriate to give
      increasing deference to the views of the child as the child grows older.

PMID- 9232511
TI  - Adolescent parents and medical decision-making.
AB  - The growing phenomenon of teenage pregnancy introduces the problem of who should
      serve as surrogate decision makers for the children of adolescent parents. The
      justifications which sanction society's grant of presumptive decision making
      authority for adult parents, and the rationales and empirical evidence supporting
      a central role for adolescents who wish to make medical decisions regarding their
      own care, together suggest that older adolescent parents should be viewed as the
      presumptive decision makers for their children. There is, however, empirical
      evidence that adolescent parents lack the cognitive abilities of childless
      adolescents of the same age and that many exhibit lower levels of emotional
      stability, sensitivity to infant needs, and social adjustment. These
      deficiencies, where present, undermine the very justifications for allowing
      adolescents to make medical decisions for their children. These findings are
      strong enough to justify a greater level of watchfulness over the competency and
      decisions of those adolescents who wish to make decisions for their children, but
      not definitive enough to conclude that, as a group, they be presumed incapable of
      making those decisions.

PMID- 9232512
TI  - The best-interests standard as threshold, ideal, and standard of reasonableness.
AB  - The best-interests standard is a widely used ethical, legal, and social basis for
      policy and decision-making involving children and other incompetent persons. It
      is under attack, however, as self-defeating, individualistic, unknowable, vague,
      dangerous, and open to abuse. The author defends this standard by identifying its
      employment, first, as a threshold for intervention and judgment (as in child
      abuse and neglect rulings), second, as an ideal to establish policies or prima
      facie duties, and, third, as a standard of reasonableness. Criticisms of the best
      interests standard are reconsidered after clarifying these different meanings.

PMID- 9232513
TI  - Prodrug strategies based on intramolecular cyclization reactions.
AB  - Several new prodrug systems for amines, alcohols, and peptides are reviewed. The
      design of these new prodrug systems takes advantage of several facile
      intramolecular cyclization reactions, that permit separate manipulation of the
      release kinetics independent of the structural features of the drug moiety. Such
      systems can be used for the preparation of esterase-, phosphatase-, and redox
      sensitive prodrugs of amines and alcohols and esterase-sensitive cyclic prodrugs
      of peptides and peptide mimetics.

PMID- 9232515
TI  - A cellular automata model of diffusion in aqueous systems.
AB  - A cellular automata model of a solute diffusing in water has been created and
      studied for the influential attributes. The results with this model are in
      agreement with experimental results; that is, that lipophilic solutes diffuse
      faster than do polar solutes. The model reveals that a solution composed of a
      relatively lipophilic solute permits a greater extent of diffusion of another
      solute. This observation is in agreement with the model showing a diffusion
      preference of a solute between two solutions made up of differing polarities. The
      solute diffuses farther into the lipophilic solution. A temperature-lipophilicity
      phase diagram shows the influence of these two attributes on the rate of
      diffusion. A model of diffusion through solutions containing stationary
      ingredients reveals a faster rate when the ingredient is lipophilic. We are led
      to a conclusion that the relative lipophilicity of solutes or stationary
      ingredients in a solution has a direct influence on the rates of diffusion of
      other solutes in their midst.

PMID- 9232514
TI  - A radioimmunoassay for LY315902, an analog of glucagon-like insulinotropic
      peptide, and its application in the study of canine pharmacokinetics.
AB  - Glucagon-like insulinotropic peptide (GLP-1) and its analogs are of interest
      because of their therapeutic potential in type II diabetes. LY315902 is a GLP-1
      (7-37)-OH analog with a modified N-terminus (IP7), an octanoic acid (C8) acylated
      on the lysine residue at position 34, and a substitution with arginine at
      position 26. We developed a sensitive and specific radioimmunoassay (RIA) for the
      determination of immunoreactive LY315902 in the plasma of animals. A
      homobifunctional cross-linker was used to couple the nonacylated form of LY315902
      [IP7-R26-GLP-1-(7-37)-OH] to carrier proteins to enhance its immunogenicity.
      Following immunization, animal antisera were screened by RIA for the presence of
      LY315902 antibodies. One rabbit produced a high-affinity antiserum that display
      insignificant cross-reactivity against two forms of native GLP-1 and possible
      major metabolites of LY315902. In this RIA method, plasma samples were combined
      with radioiodinated LY315902 and rabbit anti-IP7-R26-GLP-1-(7-37)-OH serum, and
      then incubated overnight at room temperature. The bound forms of LY315902 were
      separated by polyethylene glycol assisted second antibody precipitation. The
      sensitivity of the assay was estimated to be 19 pM. Inter-assay precision (%CV)
      and accuracy (recovery) for quality control samples in dog plasma ranged from
      8.0% to 14.7% and 92.8% to 107.3%, respectively. By applying this assay to
      measure plasma concentrations of immunoreactive LY315902 in dogs following twice
      daily subcutaneous injections of LY315902, we determined that the plasma half
      life of LY315902 is significantly longer than that of native GLP-1-(7-37)-OH. We
      concluded that the structural modifications which were made to produce LY315902
      prolonged its plasma half-life. The extended plasma half-life of LY315902
      correlated well with its prolonged pharmacology in dogs.

PMID- 9232516
TI  - Effects of absorption enhancers on the transport of model compounds in Caco-2
      cell monolayers: assessment by confocal laser scanning microscopy.
AB  - Three typical absorption enhancers, i.e., sodium caprate (Cap-Na), sodium
      deoxycholate (Deo-Na), and dipotassium glycyrrhizinate (Grz-K), were compared in
      terms of their permeability-enhancing effects on hydrophilic and hydrophobic
      model compounds in Caco-2 cell monolayers. The transepithelial electrical
      resistance (TEER) of the monolayers was reduced concentration-dependently by
      treatment with Cap-Na and Deo-Na, while treatment with Grz-K increased the TEER.
      Two patterns of TEER reduction were observed: one pattern indicated that Cap-Na
      had a rapid reducing effect, and another indicated that Deo-Na had a delayed
      reducing effect. These reductions in the TEER were accompanied by the increased
      transepithelial transport of two hydrophilic model compounds, sodium fluorescein
      (Flu-Na; MW = 376, log P = -1.52) and fluorescein isothiocyanate-dextran 4000 (FD
      4; MW = 4400, log P = -2.0), and one hydrophobic model compound, rhodamine 123
      hydrate (Rh123; MW = 381, log P = 1.13). The transport-enhancing effects of Cap
      Na and Deo-Na on these model compounds decreased in the following order: FD-4 >
      Rh123 > Flu-Na, while Grz-K was found to have no effect on the transport of any
      of these model compounds. Confocal laser scanning microscopy (CLSM) of Caco-2
      cell monolayers revealed that Cap-Na and Deo-Na enhanced the transepithelial
      transport of the hydrophilic model compounds via the paracellular route and that
      of the hydrophobic model compound via both paracellular and transcellular routes.
      Semiquantitative visual information obtained from CLSM images reflected the
      results of the transport experiment.

PMID- 9232517
TI  - Contribution of trypsin-sensitive proteins to binding of cationic liposomes to
      the mouse macrophage-like cell line RAW264.7.
AB  - We studied the binding of cationic liposomes, including didodecyl N-(alpha
      (trimethylammonio)acetyl)-D-glutamate chloride (TMAG), to a mouse macrophage-like
      cell line RAW264.7 to clarify which molecules contribute to the binding of TMAG
      liposomes to the cell surface. Several types of TMAG liposomes encapsulating
      [3H]inulin, intra-aqueous markers of liposomes, were prepared and their binding
      characteristics were compared with those of neutral and negatively charged
      liposomes. The binding of TMAG liposomes to cells was superior to those of
      neutral and negatively charged liposomes and increased with increasing TMAG
      content. Scatchard plots for the binding of TMAG liposomes to the cells were
      approximately linear, indicating a single class of binding sites. Pretreatment of
      the cell surface with heparinase, heparitiase, chondroitinase ABC, or
      neuraminidase did not reduce the binding of TMAG liposomes. These results
      suggested that neuraminic acid and glycosaminoglycan on the cell surface have
      little contribution to TMAG liposome binding. Pretreatment of the cells with
      trypsin reduced the binding of TMAG liposomes in a concentration-dependent manner
      but did not detach the cells from the culture plates. In addition, alpha
      chymotrypsin pretreatment had no effect even up to 5 micrograms/mL. Post
      treatment with trypsin enhanced the release of TMAG liposomes from the cell
      surface in a concentration-dependent manner. These results demonstrated that TMAG
      liposomes bind to trypsin-sensitive proteins on the cell surface.

PMID- 9232518
TI  - Percutaneous absorption of sunscreen agents from liquid paraffin: self
      association of octyl salicylate and effects on skin flux.
AB  - This study provides an investigation of the availability of octyl salicylate
      (OS), a common sunscreen agent, from liquid paraffin and the effect of OS on skin
      permeability. A model membrane system to isolate the vehicle effect from membrane
      permeability has been developed. Partitioning of OS between liquid paraffin and
      aqueous receptor phases was conducted. Partition coefficients increased with
      increase in OS concentration. A range of OS concentrations in liquid paraffin was
      diffused across human epidermis and synthetic membranes into 4% bovine serum
      albumin in phosphate-buffered saline and 50% ethanol. Absorption profiles of OS
      obtained from silicone and low-density polyethylene (LDPE) membranes were similar
      to each other but higher than for the high-density polyethylene [HDPE (3 times)]
      membrane and human epidermis (15 times). The steady state fluxes and apparent
      permeability coefficients (Kp') obtained from the diffusion studies showed the
      same trends with all membranes, except for the HDPE membrane which showed greater
      increase in flux and Kp' at concentrations above 30%. IR spectra showed that
      several bands of OS were shifted with concentrations, and the molecular models
      further suggested that the main contribution to the self-association is from non
      1,4 van der Waals interactions.

PMID- 9232519
TI  - Relationship of skin target site free drug concentration (C*) to the in vivo
      efficacy: an extensive evaluation of the predictive value of the C* concept using
      acyclovir as a model drug.
AB  - For the past few years, our laboratory has been involved in the development of a
      novel approach for predicting topical in vivo efficacy based on the estimation of
      skin target site free drug concentration (C*) from in vitro flux data. We have
      used acyclovir (ACV) as a model drug in the treatment of cutaneous herpes simplex
      virus type 1 infections in hairless mice. The goal of this study was to
      rigorously evaluate the applicability of this approach over the entire range of
      topical efficacy (i.e., from 0 to 100%). We employed a variety of ACV
      formulations differing in solvent compositions, enhancers, and excipients (and
      therefore in their efficacies) to achieve this goal. The C* values were estimated
      from the in vitro flux data obtained in an in vivo-in vitro experimental design
      that closely approximated the in vivo treatment protocol. For the in vivo
      antiviral efficacy studies, a finite dose of ACV formulation was applied twice a
      day, beginning the day after virus inoculation, for 4 days. The lesions were
      scored on the fifth day, and the efficacies were calculated as described earlier.
      Our results indicate that, for a variety of formulations over a wide range of
      efficacies, the predictions based on C* are in good agreement with the observed
      in vivo efficacies. These findings strongly demonstrate the predictive value of
      C* over the entire range of topical efficacy, thereby further strengthening its
      potential for future studies. The findings also indicate that although the
      excipients in a formulation may alter the rate and extent of available drug at
      the target site, in these cases, they do not seem to have any effect on the in
      vivo potency of the drug.

PMID- 9232520
TI  - Nasal absorption of dihydroergotamine from liquid and powder formulations in
      rabbits.
AB  - Nasal drug delivery is an interesting route of administration for
      dihydroergotamine in migraine therapy. The currently available formulation
      contains dihydroergotamine at 4 mg/mL. For a nasal dose of 2 mg, a volume of 0.5
      mL has to be administered, which sometimes leads to spillage of the formulation.
      The aim of the present study was to develop a nasal spray with a
      dihydroergotamine concentration of 10 mg/mL. To increase the solubility and
      stability of dihydroergotamine, randomly methylated beta-cyclodextrin was used.
      Liquid formulations and lyophilized powders of dihydroergotamine and randomly
      methylated beta-cyclodextrin were prepared. The liquid and powder formulations
      were compared by determining their pharmacokinetics and absolute bioavailability
      after nasal administration in rabbits. Nasal sprays were significantly more
      effective than drops in increasing the nasal bioavailability of
      dihydroergotamine, but the amount of randomly methylated beta-cyclodextrin in
      liquid sprays did not significantly alter the nasal absorption. For powder
      formulations, the dihydroergotamine absorption was dependent on the amount of
      methylated beta-cyclodextrin and powder volume, and the nasal bioavailability
      from the optimal powder was slightly, but not significantly, higher than that for
      liquids. In conclusion, the formulations investigated are a substantial
      improvement of the current commercial formulation, not only because the spray
      volume of the liquid spray can be reduced 2.5 times, but also because of the
      increased stability of liquid and powder sprays with randomly methylated-beta
      cyclodextrin.

PMID- 9232521
TI  - Pharmacokinetics of RheothRx injection in healthy male volunteers.
AB  - The objectives of this study were to evaluate the safety and tolerability of
      RheothRx (poloxamer 188) injection administered as an intravenous (i.v.) infusion
      to healthy male volunteers and to determine the pharmacokinetic profile of
      poloxamer 188. Thirty-six healthy male volunteers were enrolled in a randomized,
      double-blind, placebo-controlled, dose-escalation trial for RheothRx injection.
      The volunteers were randomized to three treatment groups (12 per treatment group,
      with eight receiving active therapy and four receiving placebo). In each
      treatment group, volunteers received RheothRx injection or placebo as an i.v.
      infusion on two occasions at least 3 weeks apart to make a total of six doses
      being studied (10, 30, and 45 mg/kg/h for 72 h, 60 mg/kg/h for 43.3 to 72 h, 60
      and 90 mg/kg/h for 24 h). Serial plasma samples were collected during and up to
      36 h after the end of the infusions; urine was collected over intervals from the
      start of the infusion until 36 h after the infusions were terminated. Plasma and
      urine samples were assayed for poloxamer 188 by gel-permeation chromatography.
      Pharmacokinetic parameter values were calculated by noncompartmental and
      compartmental methods. Poloxamer 188 was eliminated primarily by renal excretion.
      Estimates of clearance, elimination rate constant, and apparent volume of
      distribution at steady state values were independent of infusion rate. Poloxamer
      188 displayed no apparent infusion rate dependence in its pharmacokinetics.

PMID- 9232522
TI  - Mechanistic roles of neutral surfactants on concurrent polarized and passive
      membrane transport of a model peptide in Caco-2 cells.
AB  - The transport of the model peptide Acf(NMef)2NH2 across Caco-2 cell monolayers
      was studied in the apical (AP) to basolateral (BL) and the BL to AP direction in
      the presence of Polysorbate 80 or Cremophore EL in the AP compartment. Increasing
      surfactant concentrations resulted in increasing AP-->BL peptide permeability and
      decreasing BL-->AP permeability. In either direction, limiting permeabilities
      were achieved at concentrations less than the critical micellar concentrations
      (cmc's) of the surfactants, and remained constant at much higher concentrations.
      These plateau permeabilities were not equivalent in the two directions. This
      residual assymetry was abolished by increasing the peptide concentration.
      Altogether, the observations support the presence of at least two pumps in Caco-2
      cells for this peptide, polarized in the BL-->AP direction. These experimental
      results were analyzed within the context of a quantitative biophysical model
      incorporating concurrent passive diffusion across the AP and BL membranes
      accompanied by surfactant-inhibitable active polarized efflux across the AP
      membrane. The model was also used to locate the additional transport activity at
      the BL membrane as an uptake pump. Under conditions of complete inhibition, the
      intrinsic passive diffusional permeability of Acf(NMef)2NH2 was found to be 13 x
      10(-6) cm/s, essentially identical with results reported earlier with this
      peptide utilizing verapamil as an inhibitor. With respect to the mechanism of
      surfactant inhibition of the apical efflux transport, the monomeric species was
      found to be responsible with no contribution from micelles. Modeling the mode of
      inhibition as a noncompetitive Michaelis-Menten process gave identical Kis of 0.5
      microM for the two surfactants. Finally, increase of either surfactant beyond 750
      microM resulted in a decrease of peptide permeability in the AP-->BL direction.
      This was attributed to weak association of the peptide with micelles in the AP
      compartment, which effectively decreased the thermodynamic activity of the
      peptide at surfactant concentrations greater than 20 times their cmc. Both the
      experimental approach and accompanying theoretical model demonstrated in this
      work will allow for further characterization of the inhibitory potencies of
      surfactants for the nonpassive efflux pathway in vitro and in vivo.

PMID- 9232523
TI  - Determination of dexmedetomidine in rat plasma by a sensitive [3H]clonidine
      radioreceptor assay.
AB  - This paper describes the development and implementation of a sensitive
      radioreceptor assay (RRA) for determining concentrations of dexmedetomidine, an
      alpha-2 adrenergic agonist with anesthetic properties, in rat plasma. Calf retina
      membranes were selected as the alpha-2 adrenergic receptor source, and the alpha
      2 antagonist [3H]RX821002 and the alpha-2 agonist [3H]clonidine were evaluated as
      radioligands. We optimized the binding conditions for both radioligands and chose
      a radioligand for implementation in the RRA based on the characteristics of the
      inhibition binding curves with dexmedetomidine. The final method is based on
      competition between the radioligand [3H]clonidine and dexmedetomidine for high
      affinity binding sites present in calf retina membranes. The assay has a
      coefficient of variation of 8% in the range 23.7-592 pg for 0.2 mL of plasma.
      This assay can be applied to pharmacokinetic-pharmacodynamic studies of
      dexmedetomidine.

PMID- 9232524
TI  - Iron(III)-chelating properties of the novel catechol O-methyltransferase
      inhibitor entacapone in aqueous solution.
AB  - The iron(III) complex formation of entacapone, a novel catechol O
      methyltransferase (COMT) inhibitor, has been studied at 25 degrees C in aqueous
      0.1 mol/L NaCl solution by using the electromotive force titration method.
      Entacapone functions as a bidentate ligand chelating through the catecholate
      oxygen atoms and forms stable iron(III) complexes with the formation constant of
      a tris complex: log beta-613 ([FeL3(3-)][H]6+/[Fe3+][H2L]3) = -6.9 +/- 0.1.
      Distribution curves show that entacapone is highly effective for iron(III) in
      moderately dilute solution (10(-3) mol/L) whereas in very dilute solution (10(-6)
      mol/L) the iron hydroxo complexes together with FeL3(3-) dominate under
      physiological pH 7.4. Comparison of iron(III) species distribution in a
      competitive two-ligand entacapone-catechol system reveals that the complexation
      of entacepone is favored at high and low dilution.

PMID- 9232525
TI  - Antitumoral activity of liposomes and immunoliposomes containing 5-fluorouridine
      prodrugs.
AB  - Liposomes and immunoliposomes containing cytotoxic agents may be highly
      efficacious in intracavity therapy of malignancies confined principally to the
      peritoneal cavity. To assess the feasibility of this locoregional treatment, we
      prepared two derivatives of 5-fluorouridine (5-FUR), a highly cytotoxic
      metabolite of 5-fluorouracile, and incorporated them into REV liposomes, prepared
      with the reverse phase evaporation method. Encapsulation efficiency, drug
      leakage, and stability were determined, and size analysis and differential
      scanning calorimetry were carried out to evaluate the drug delivery potential of
      liposomes containing 5'-palmitoyl-5-FUR, 5'-succinyl-5-FUR, or the parent drug 5
      FUR. The most suitable drug for encapsulation, in terms of minimum leakage and
      encapsulation efficiency, was 5'-palmitoyl-5-FUR, which differential scanning
      calorimetry indicated as being firmly anchored to the lipid bilayer. Thus, 5'
      palmitoyl-5-FUR was chosen to prepare a chemotherapeutic liposome-monoclonal
      antibody conjugate (immunoliposome). The covalent linkage between antibody and
      liposome was realized by coupling the thiolated monoclonal antibody AR-3 with REV
      liposomes, containing N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine.
      The cytotoxic activity of drug-bearing liposomes and immunoliposomes was
      evaluated on the HT-29 human colon adenocarcinoma cell line; the immunoliposomes
      had higher cytotoxicity than liposomes or 5-FUR. To explore the potential of
      these drug formulations in anticancer therapy, we ip injected liposomes or
      immunoliposomes into athymic mice ip grafted with human HT-29 cell line. In this
      mouse model, the immunoliposome containing 5'-palmitoyl-5-FUR displayed the best
      antitumoral activity, since on day 27 postgraft only 5% of residual tumor mass
      was present, compared to control mice; there was a close relationship between
      exposure time of tumor tissue to the drug and antitumor potency.

PMID- 9232526
TI  - Application of neural networks to population pharmacokinetic data analysis.
AB  - This research examined the applicability of using a neural network approach to
      analyze population pharmacokinetic data. Such data were collected retrospectively
      from pediatric patients who had received tobramycin for the treatment of
      bacterial infection. The information collected included patient-related
      demographic variables (age, weight, gender, and other underlying illness), the
      individual's dosing regimens (dose and dosing interval), time of blood drawn, and
      the resulting tobramycin concentration. Neural networks were trained with this
      information to capture the relationships between the plasma tobramycin levels and
      the following factors: patient-related demographic factors, dosing regimens, and
      time of blood drawn. The data were also analyzed using a standard population
      pharmacokinetic modeling program, NON-MEM. The observed vs predicted
      concentration relationships obtained from the neural network approach were
      similar to those from NONMEM. The residuals of the predictions from neural
      network analyses showed a positive correlation with that from NONMEM. Average
      absolute errors were 33.9 and 37.3% for neural networks and 39.9% for NONMEM.
      Average prediction errors were found to be 2.59 and -5.01% for neural networks
      and 17.7% for NONMEM. We concluded that neural networks were capable of capturing
      the relationships between plasma drug levels and patient-related prognostic
      factors from routinely collected sparse within-patient pharmacokinetic data.
      Neural networks can therefore be considered to have potential to become a useful
      analytical tool for population pharmacokinetic data analysis.

PMID- 9232527
TI  - Structure-permeation relations of met-enkephalin peptide analogues on absorption
      and secretion mechanisms in Caco-2 monolayers.
AB  - Due to the low effective permeabilities of peptides at many absorption sites,
      their structure-permeation relations are of high interest. In this work structure
      permeation relations of Met-enkephalin analogues are presented using confluent
      Caco-2 cells as an in vitro permeation model. Four model peptides (Met
      enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid)
      were tested in terms of permeability, lipophilicity, charge, and molecular size.
      Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to
      9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No
      correlation of permeability and the log(apparent octanol/buffer partition
      coefficient) was observed. A 40-fold increase of the permeability of metkephamid
      in the presence of 10 mM EDTA suggested a significant contribution of
      paracellular transport. Independent support for this conclusion was obtained by
      visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by
      confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was
      observed in the intercallular space only. Metkephamid permeabilities were found
      to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were
      significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The
      addition of verapamil equalized the permeabilities in the a-to-b and b-to-a
      directions, suggesting the involvement of a P-glycoprotein-mediated secretion
      mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide,
      but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other
      analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at
      neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met
      enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met
      enkephalin). The data is in agreement with the literature showing that most
      compounds secreted by the P-glycoprotein transporter carry a positive charge.

PMID- 9232528
TI  - Ketoprofen sodium: preparation and its formation of mixed crystals with
      ketoprofen.
AB  - A simple two-step process for the preparation of ketoprofen sodium was developed.
      The procedure involved dissolution of ketoprofen in ethanolic NaOH followed by
      evaporation of the solvent. The resulting amorphous solid was crystallized by
      controlled precipitation from 96% ethanol. The sodium salt proved to be stable
      for 4 years and its aqueous solutions for at least 1 year (investigated period).
      Ketoprofen sodium appears to be an alternative bulk form to ketoprofen acid for
      production of formulations after further characterization of the compound.

PMID- 9232529
TI  - Development of a cell culture system to study antibody convection in tumors.
AB  - The convective transport of fluid and of a binding antibody through a cultured
      tumor cell layer was investigated with a mouse melanoma cell line (B16F10) grown
      on a microporous polycarbonate filter (Snapwell inserts). The inserts were
      precoated with Matrigel or collagen, or were uncoated. The cell layers were
      exposed to nominal pressure gradients from 5 to 25 cm H2O, and the volume flux
      was measured by collecting the effluent volume over time. The rate of convective
      transport of a binding monoclonal antibody that recognizes the murina transferrin
      receptor (a-TfR) was investigated at a nominal pressure gradient of 15 cm H2O and
      compared with that of an isotype matched, nonbinding control. The resistance, R,
      of the cell layer to fluid flow was quantified as the hydraulic conductivity, Lp
      (= 1/R); the ability of the cell layer to retard antibody transport was
      quantified as the reflection coefficient, sigma. The resulting Lp values
      decreased with increasing cell density, in a manner consistent with Poiseuille
      flow. Collagen or Matrigel precoating also decreased Lp values, with cells grown
      on Matrigel providing the greatest resistance. The sigma values were 0.67 (+/
      0.08) for the a-TfR antibody and 0.51 (+/-0.06) for the control, indicating that
      the cell layer acts as a semipermeable barrier to convective transport of
      antibody that is less permeable to the binding antibody.

PMID- 9232530
TI  - Prediction of distribution coefficient from structure. 1. Estimation method.
AB  - A method has been developed for the estimation of the distribution coefficient
      (D), which considers the microspecies of a compound. D is calculated from the
      microscopic dissociation constants (microconstants), the partition coefficients
      of the microspecies, and the counterion concentration. A general equation for the
      calculation of D at a given pH is presented. The microconstants are calculated
      from the structure using Hammett and Taft equations. The partition coefficients
      of the ionic microspecies are predicted by empirical equations using the
      dissociation constants and the partition coefficient of the uncharged species,
      which are estimated from the structure by a Linear Free Energy Relationship
      method. The algorithm is implemented in a program module called PrologD.

PMID- 9232531
TI  - Modifications in high-density lipoprotein lipid composition and structure alter
      the plasma distribution of free and liposomal annamycin.
AB  - Recent studies have shown that changes in lipoprotein cholesterol and
      triglyceride concentration alters the plasma distribution of free (Ann.) and
      liposomal annamycin (LAnn) and that the majority of Ann. is associated with high
      density lipoproteins (HDL) following the incubation in plasma of LAnn. To
      demonstrate that alterations in HDL lipid composition and HDL structure may
      influence the plasma distribution of Ann. and LAnn, Ann. and LAnn (20
      micrograms/mL) were incubated in plasma pretreated with dithionitrobenzoate
      (DTNB, a compound which inhibits the conversion of free cholesterol to esterified
      cholesterol) 18 h prior to the experiment or in untreated plasma for 60 min at 37
      degrees C. In addition, Ann. and LAnn were co-incubated with DTNB in plasma for
      60 min at 37 degrees C. Following incubation the plasma was separated into its
      HDL, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and
      lipoprotein-deficient plasma (LPDP) fractions by ultracentrifugation and assayed
      for Ann. by fluorimetry. The HDL plasma cholesterol:triglyceride concentration
      ratio was significantly decreased following 18 h of DTNB pretreatment compared to
      untreated plasma controls. No significant differences in LDL/VLDL plasma
      cholesterol:triglyceride concentration ratio following 18 h of DTNB pretreatment
      was observed. An increased number of discoidal HDL particles were observed
      following 18 h of DTNB pretreatment. When Ann. was incubated in plasma pretreated
      with DTNB for 18 h the percentage of Ann. recovered in the HDL, LDL, and VLDL
      fractions significantly increased. However, the percentage of Ann. recovered
      within the LPDP fraction was significantly decreased. When LAnn was incubated in
      plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL
      fraction significantly decreased. The percentage of Ann. recovered in the LPDP
      fraction significantly increased when LAnn was incubated in plasma pretreated
      with DTNB for 18 h. No significant differences in Ann. lipoprotein distribution
      were observed when Ann. and LAnn were co-incubated with DTNB in plasma for 1 h.
      These findings suggest that the cholesterol:triglyceride concentration ratio and
      physical structure of HDL maybe important in defining the capacity of HDL to
      sequester Ann.

PMID- 9232532
TI  - Administration of long-term tamoxifen therapy modifies the plasma lipoprotein
      lipid concentration and lipid transfer protein I activity in postmenopausal women
      with breast cancer.
AB  - Tamoxifen remains one of the most effective agents in the treatment of breast
      cancer. However, the development of persistent side effects from chronic
      administration of tamoxifen remains a concern. The objective of this project was
      to investigate the effect of long-term tamoxifen therapy (2 years) on the plasma
      lipoprotein concentration and lipid transfer activity in postmenopausal women
      diagnosed with breast cancer. Two distinct populations of breast cancer patients
      were recruited for this study: postmenopausal women diagnosed with breast cancer
      that have never been on tamoxifen and postmenopausal women diagnosed with breast
      cancer that have been on tamoxifen (20 mg once daily) for 2 years (n = 18 each
      group). Blood was collected for total and lipoprotein cholesterol (C) and
      triglyceride (TG) analysis by established enzymatic assays prior to and 2 years
      following the initial tamoxifen dose. To determine the effect of tamoxifen
      administration on lipid transfer between lipoprotein fractions, lipid transfer
      protein (LTP I) activity was measured. A significant decrease in total and low
      density lipoprotein (LDL) cholesterol levels and a moderate increase in high
      density lipoprotein (HDL) triglyceride levels were observed in plasma samples
      from postmenopausal women with breast cancer who were administered tamoxifen for
      2 years. No significant differences in total and lipoprotein C and TG plasma
      levels were observed in samples from women with breast cancer that never received
      tamoxifen. LTP I activity was significantly decreased in patients receiving
      tamoxifen compared to patients who never received tamoxifen. These specific
      tamoxifen-induced effects may be important for a number of reasons. Although the
      apparent decrease in total C and LDL-C levels are favorable for reducing the risk
      of cardiovascular disease, the elevated levels of HDL-TG have been related to the
      increased risk of ischemic heart disease. Furthermore, understanding how
      tamoxifen influences LTP I activity provides valuable insight into how the
      administration of tamoxifen modifies plasma lipoprotein-lipid levels.

PMID- 9232533
TI  - Ibuprofen and paracetamol: relative safety in non-prescription dosages.

PMID- 9232534
TI  - Modelling of the void space of tablets compacted over a range of pressures.
AB  - A previously developed computer model, named Pore-Cor, has been used to simulate
      the changes in the void-space dimensions which occur during the compaction of
      tablets over a range of pressures. The tablets were made by mixing pharmaceutical
      grade crystalline lactose and an anti-inflammatory compound in the proportion
      4:1. Compacts were made by placing a weighed amount of the mixed powder into a
      stainless-steel die and applying pressure with a hand-operated calibrated
      hydraulic press. Compacts were prepared at eight pressures over the hydraulic
      pressure range 1 to 8 ton in-2 (15.4-123.2 MPa) in 1 ton in-2 increments. Mercury
      intrusion curves were measured for the eight samples by use of a porosimeter and
      the Pore-Cor package was then used to simulate the mercury-intrusion curves and
      generate void-space models of the correct porosity. The experimental and
      simulated characteristic throat diameter, the experimental and simulated
      porosity, and the simulated permeability of the tablets have all been shown to
      follow expected trends. The successful modelling of void-structure parameters,
      which are difficult or impossible to measure experimentally, opens the way to an
      improved understanding of the strength of compacts.

PMID- 9232535
TI  - Effects of grinding and humidification on the transformation of conglomerate to
      racemic compound in optically active drugs.
AB  - The effects of grinding and humidification on the transformation of conglomerate
      to racemic compound have been investigated by X-ray powder diffraction (XPD),
      differential scanning calorimetry (DSC) and infrared (IR) spectroscopy for
      leucine, norleucine, valine, serine, tartaric acid and malic acid. Racemic
      physical mixtures were prepared by physical mixing of equimolar quantities of D
      and I. crystals using a mortar and pestle. Ground mixtures were obtained by
      grinding the physical mixtures with a vibrational mill. Humidification was
      performed by storing the physical mixtures and the ground mixtures in a
      desiccator containing saturated aqueous salt solutions at 40 degrees C. When
      physical mixtures of malic acid, tartaric acid and serine were ground, the XPD
      peaks of the racemic compounds were observed. The XPD patterns of humidified
      physical mixtures of these compounds also showed the formation of the racemic
      compounds. This indicated that grinding or humidification of malic acid, tartaric
      acid and serine induced the transformation of conglomerate to racemic compound
      crystals. When, on the other hand, the physical mixtures of valine, leucine and
      norleucine were ground, peaks of racemic compounds were not detected in the XPD
      pattern. After humidification of the ground mixtures of valine, leucine and
      norleucine, however, the XPD peaks of racemic compounds were observed. DSC and IR
      studies revealed consistent results. We concluded that grinding or humidification
      of malic acid, tartaric acid and serine could induce the transformation of a
      conglomerate to racemic compound. In contrast, humidifying after grinding was
      needed to bring about the transformation in leucine, norleucine and valine.

PMID- 9232536
TI  - Physical stability of solid dispersions containing triamterene or temazepam in
      polyethylene glycols.
AB  - The effect of storage on the physical stability of solid dispersions of
      triamterene or temazepam in polyethylene glycols was studied using differential
      scanning calorimetry (DSC), particle-size analysis and dissolution methods. The
      enthalpies of fusion of the carriers, without included drug and previously fused
      and crystallized, increased on storage. Analysis of similarly treated solid
      dispersions, containing either 10% temazepam or 10% triamterene, showed that each
      drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies
      and melting points of the solidus components of the dispersions' carriers were
      initially reduced after preparation, but on storage these increased. The particle
      sizes of the drugs dispersed in the PEGs increased on storage. The changes in
      dissolution after storage of triamterene or temazepam dispersions were smaller
      for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular
      weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was
      particularly marked during the first month of storage. The rank order of changes
      in dissolution were PEG 1500 < < PEG 2000 < PEG 4000 approximately PEG 6000.

PMID- 9232537
TI  - Characterization of the influence of some cyclodextrins on the stratum corneum
      from the hairless mouse.
AB  - Differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)
      spectroscopy and transmission electron microscopy (TEM) have been used to
      determine the influence of beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-CyD
      (HP-beta-CyD) and gamma-CyD on the structural properties of the stratum corneum
      from the hairless mouse. Some modest changes in the stratum corneum lipid
      transition temperature were induced by HP-beta-CyD and blue shifts were observed
      in the FTIR spectra of the C-H asymmetric and symmetric stretching of the lipids
      from the stratum corneum. Results from TEM studies indicated that HP-beta-CyD
      caused removal and possible disorganization of the lipid matrix that envelopes
      the corneocytes of the stratum corneum, whereas no effect was seen after
      treatment of the samples with beta-CyD and gamma-CyD. These results suggest that
      HP-beta-CyD can increase the permeability of the stratum corneum possibly as a
      result of extraction of lipids, and might thus enhance drug permeation through
      the skin.

PMID- 9232538
TI  - A comparison of the physicochemical and biological properties of mirtazapine and
      mianserin.
AB  - Although the chemical structures of the antidepressants mirtazapine and mianserin
      are closely related there are considerable differences in their biological
      properties. To find an explanation of this, various physicochemical properties of
      mirtazapine and mianserin were measured or calculated. Isosteric replacement of
      CH in mianserin by N in mirtazapine has profound effects on physicochemical
      properties. The charge distributions as indicated by NMR and calculated by semi
      empirical quantum mechanics differ, not only for the changed aromatic A-ring (as
      expected), but also in other regions of the molecule. The N5 atom in particular,
      which is conjugated to the changed aromatic ring, is less negatively charged in
      mirtazapine than in mianserin. Consequently the oxidation potential of
      mirtazapine is significantly higher than that of mianserin. Another result of
      this difference in charge distribution is that the (calculated) dipole-moment
      vectors of the compounds are oriented roughly perpendicular to each other. The
      dipole moment of mirtazapine is, moreover, three times larger than that of
      mianserin; mirtazapine is, therefore, more polar than mianserin and this is
      reflected in a lower retention index. Finally, the basicity of mirtazapine,
      expressed as the pKa value, is slightly but significantly lower than that of
      mianserin. The observed differences between the physicochemical properties of
      mirtazapine and mianserin result in different interactions of these two
      antidepressants with macromolecules, such as receptors, transporters and
      metabolizing enzymes; this might explain the differences observed in
      pharmacological activity and metabolic and kinetic behaviour, that is, the
      reduced affinity for the alpha 1-adrenoceptor and negligible noradrenaline
      reuptake of mirtazapine compared with mianserin.

PMID- 9232540
TI  - Neuromuscular blockade: offset anomalies. Are they simply potency-related
      receptor bonding effects?
AB  - Rapid making and breaking of bonds between quaternary ammonium compounds and
      cholinergic receptors is typical of ion-pair bonding, which is weak, and ion-pair
      reactions, which are extremely fast. These properties explain the observed rapid
      association and dissociation of turbocurarine at receptors. The time course
      receptor offset is determined by two factors, buffered diffusion due to
      repetitive bonding, and a potency-related offset-retarding effect. The strength
      of the latter is a function of chemical structure, which determines the
      microscopic molecular rate of drug-receptor association and dissociation.
      Together, buffered diffusion and the potency-related offset-retarding effect
      provide a complete rational physico-chemical explanation for the marked, yet
      variable, differences between onset and offset times of non-depolarizing
      neuromuscular blocking agents. The influence of a potency-related offset
      retarding effect together with differing structural requirements for
      neuromuscular blocking potency and plasma carboxyesterase hydrolysis, suggests
      that a high potency ultrashort duration block is unlikely to be achieved in a non
      depolarizing compound metabolized by plasma esterases alone.

PMID- 9232539
TI  - Behavioural subsensitivity induced by long-term administration of a low dose of
      haloperidol to rats.
AB  - This study examines the effects on open-field and stereotyped behaviour of rats
      of abrupt withdrawal from repeated treatment with a low (0.03 mg kg-1) dose of
      haloperidol. Single administration of this low dose of haloperidol significantly
      increased open-field locomotion without modifying apomorphine (0.5 or 2.0 mg kg
      1)-induced stereotyped behaviour. Forty-eight hours after abrupt withdrawal from
      0.03 mg kg-1 haloperidol (twice daily for 15 days) a significant decrease in
      locomotion frequency was observed, but no change was observed in apomorphine
      induced stereotypy. Our results suggest that dopamine autoreceptor
      supersensitivity might be evaluated in a behavioural situation of absence of
      postsynaptic dopamine receptor supersensitivity.

PMID- 9232541
TI  - Antihypertensive effect of some oxazolo[3,2-a]pyridines, thiazolo[3,2-a]pyridines
      and pyrido[2,1-b]oxazines in conscious spontaneously hypertensive rats.
AB  - The antihypertensive activity of eighteen 'oxazolo[3,2-a]pyridine, thiazolo[3,2
      a]pyridine and pyrido[2,1-b]oxazine derivatives has been evaluated in conscious
      spontaneously hypertensive rats (SHRs), and compared with that of nifedipine,
      used as reference. At a dose of 50 mg kg-1 (i.p.) eleven compounds resulted in a
      significant reduction in mean arterial blood pressure; four of the eleven were
      particularly effective, resulting in significant hypotension more than 6 h after
      administration and an effect that was still apparent after 24 h. The hypotension
      induced by nifedipine gradually decreased, disappearing 6-8 h after
      administration. The long-lasting activity shown by these compounds is, in
      general, not accompanied by reflex tachycardia. Intraperitoneal administration of
      two oxazolo[3,2-a]pyridine derivatives and two pyrido[2,1-b]oxazine derivatives
      resulted in potent and long-lasting antihypertensive action in SHRs. Further
      studies on the mechanism of action of these derivatives might help the
      determination of better structure-activity correlations and the design, synthesis
      and evaluation of better antihypertensive agents.

PMID- 9232542
TI  - The mechanism of excretion of trientine from the rat kidney: trientine is not
      recognized by the H+/organic cation transporter.
AB  - Trientine dihydrochloride is used to treat Wilson's disease by chelating copper
      and increasing its urinary excretion. The mechanism of renal excretion of
      trientine has been investigated in-vivo and in-vitro. Trientine clearance in the
      rat-was significantly faster than creatinine clearance. When trientine and the
      same number of moles of copper ions were administered simultaneously to the rat,
      however, trientine clearance decreased to almost the same level as the creatinine
      clearance. To clarify this active excretion system for trientine, the uptake of
      trientine and a physiological polyamine compound, spermine, was investigated
      using rat renal brush-border membrane vesicles. Although, because trientine and
      spermine are organic cations, the H+/organic cation transporter is expected to
      recognize these compounds, neither an outwardly directed H+ gradient nor an
      inward Na+ gradient stimulated trientine uptake. [14C]Spermine uptake was,
      nevertheless, trans-stimulated by both unlabelled spermine and trientine and the
      trans-stimulating effect of spermine on trientine uptake was, furthermore,
      completely abolished by addition of copper ions to the incubation medium. These
      results suggest that there is a specific transport system for spermine and
      trientine on the renal brushborder membrane. This transport system contributes to
      the secretion of trientine in the kidney proximal tubule but does not recognize
      the trientine-copper complex.

PMID- 9232543
TI  - Role of the endothelium in the relaxation induced by propofol and thiopental in
      isolated arteries from man.
AB  - Induction of anaesthesia with intravenous propofol and thiopental is often
      accompanied by hypotension. This study evaluates whether propofol and thiopental
      induce relaxation of isolated arteries from man and whether this effect is
      modulated by the endothelium. Mesenteric artery rings (with and without
      endothelium) from 12 patients were placed in organ baths and precontracted with
      phenylephrine before addition of propofol (10(-3) M) or thiopental (10(-3) M).
      Relaxation induced by propofol and thiopental was evaluated for rings with intact
      endothelium in the presence of the nitric oxide synthase inhibitor NG-nitro-L
      arginine methyl ester (L-NAME; 10(-4) M) or the cyclooxygenase inhibitor
      indomethacin (10(-5) M). The vasodilator effect of propofol was similar for
      intact and denuded endothelium rings whereas the relaxation induced by thiopental
      was significantly attenuated in denuded-rings. In intact endothelium rings, L
      NAME and indomethacin caused marked inhibition of the relaxation induced by
      thiopental, but not that induced by propofol. These results suggest that propofol
      induces endothelium-independent relaxation of isolated mesenteric arteries in
      man, whereas thiopental causes endothelium-dependent relaxation mediated by
      nitric oxide and prostaglandins.

PMID- 9232544
TI  - Analysis of the role of nitric oxide in the relaxant effect of the crude extract
      and fractions from Eugenia uniflora in the rat thoracic aorta.
AB  - This study has evaluated the possible role played by the L-arginine-nitric oxide
      pathway in the vasorelaxant action of the hydroalcoholic extract from Eugenia
      uniflora, and fractions from the extract, in rings of rat thoracic aorta. The
      addition of an increasing cumulative concentration of hydroalcoholic extract from
      E. uniflora (1-300 micrograms mL-1) caused a concentration-dependent relaxation
      response in intact endothelium-thoracic aorta rings pre-contracted with
      noradrenaline (30-100 nM). The IC50 value, with its respective confidence limit,
      and the maximum relaxation (Rmax) were 7.02 (4.77-10.00) micrograms mL-1 and
      83.94 +/- 3.04%, respectively. The removal of the endothelium completely
      abolished these responses. The nitric oxide synthase inhibitors N omega-nitro-L
      arginine (L-NOARG, 30 microM) and N omega-nitro-L-arginine methyl ester (L-NAME,
      30 microM), inhibited the relaxation (Rmax) to -10.43 +/- 7.81% and -3.69 +/-
      2.62%, respectively. In addition, L-arginine (1 mM), but not D-arginine (1 mM),
      completely reversed inhibition by L-NOARG. Methylene blue (30 microM), a soluble
      guanylate cyclase inhibitor, reduced the relaxation induced by the extract to
      14.60 +/- 7.40%. These data indicate that in the rat thoracic aorta the
      hydroalcoholic extract, and its fractions, from the leaves of E. uniflora have
      graded and endothelium-dependent vasorelaxant effects.

PMID- 9232545
TI  - Polyhydroxylated C60, fullerenol, a novel free-radical trapper, prevented
      hydrogen peroxide- and cumene hydroperoxide-elicited changes in rat hippocampus
      in-vitro.
AB  - The role of polyhydroxylated C60 (fullerenol), a novel free-radical trapper, in
      prevention of hydrogen peroxide- and cumene hydroperoxide-elicited damage was
      studied in hippocampal slices from the rat in-vitro. The interactions of
      polyhydroxylated C60, adenosine and 6,7-dinitroquinoxaline-2,3-dione (DNQX) were
      also compared. Hydrogen peroxide (0.006-0.02%) and cumene hydroperoxide (0.5-1.0
      mM) both reversibly reduced the amplitudes of CA1-evoked population spikes in the
      hippocampal slices. Deferoxamine (1 mM) had little effect on the population
      spikes. Deferoxamine (1 mM) significantly prevented the hydrogen peroxide
      (0.006%) elicited inhibition of the population spikes. Polyhydroxylated C60 (0.1
      mM) significantly prevented hydrogen peroxide- or cumene hydroperoxide-elicited
      reduction of the population spikes and also prevented the effects of hydrogen
      peroxide and cumene hydroperoxide on paired-pulse facilitation in the hippocampal
      slice. Adenosine reduced the amplitude of population spikes and promoted paired
      pulse facilitation in the CA1 region of the hippocampus. Polyhydroxylated C60 did
      not alter either of the effects of adenosine on the population spikes. DNQX
      reduced the amplitude of the population spikes in the CA1 region but did not
      affect the ratio of paired-pulse facilitation. Fullerenol did not alter either
      effect of DNQX on the population spikes. These results suggested that
      polyhydroxylated C60 prevented hydrogen peroxide- and cumene hydroperoxide
      elicited damage in the hippocampuss slices. These effects might be associated
      with the free-radical scavenging activity of polyhydroxylated C60.

PMID- 9232546
TI  - Biochemical basis for deficient paracetamol glucuronidation in cats: an
      interspecies comparison of enzyme constraint in liver microsomes.
AB  - Unlike most other mammalian species, domestic cats glucuronidate phenolic
      compounds poorly and are therefore highly susceptible to the toxic side effects
      of many drugs, including paracetamol. In this study, we evaluated the role of
      enzyme constraint, a characteristic that limits the activity of all uridine 5'
      diphosphoglucuronosyltransferase (UGT) enzymes, in the aetiology of this species
      dependent defect of drug metabolism. Detergent activation experiments were
      performed using hepatic microsomes from cats (4), dogs (4), man (4), and 6 other
      mammalian species (1 liver each). In addition, we used microsomes from Gunn rats
      which are sensitive to paracetamol toxicity because of a genetic defect affecting
      all family 1 UGTs. Increase in paracetamol-UGT activity at optimum concentrations
      of detergent was used as an index of enzyme constraint. Native activity (measured
      in the absence of detergent) was less than one-sixth in cats compared with other
      species. Optimum detergent treatment tended to enhance rather than abolish this
      difference, however, indicating relatively lower levels of constraint of
      paracetamol-UGT in cats compared with other species. Similarly, detergent
      treatment failed to reduce the native activity difference between homozygous
      mutant and normal Gunn rats. Initially CHAPS (3-(3-cholamidopropyl)
      dimethylammonio-1-propanesulphonic acid) was used as the detergent activator; in
      3 of 4 microsomal preparations from man, however, inhibition rather than
      activation was observed at all detergent concentrations used. Studies were
      repeated using the non-ionic detergent, Brij 58 (polyoxyethylene 20-cetyl ether),
      which resulted in similar although more profound activation and no inhibition. We
      conclude that deficient paracetamol glucuronidation in cats does not result from
      increased paracetamol-UGT constraint in this species compared with other
      mammalian species. Other causes, such as differences in enzyme protein
      concentration or substrate affinity might be responsible.

PMID- 9232547
TI  - Prediction of the plasma concentration profiles of orally administered drugs in
      rats on the basis of gastrointestinal transit kinetics and absorbability.
AB  - A new method based on gastrointestinal transit kinetics has been developed for
      estimation of the absorption profiles of drugs administered orally as aqueous
      solutions. The utility of the method was evaluated in rats. The gastrointestinal
      transit profile for each segment was estimated by in-vivo studies using phenol
      red, an unabsorbable marker. The gastrointestinal transit profile of phenol red
      was well explained by a linear gastrointestinal transit kinetic model with eight
      segments. We also introduced the absorption process into the gastrointestinal
      transit kinetic model and the plasma profile was predicted by the convolution
      method. The absorbability of drugs in each segment was assessed by an in-situ
      absorption study. The validity of the model was evaluated for model drugs with
      different absorption characteristics. The plasma profiles predicted for
      ampicillin, theophylline and cephalexin were in good agreement with those
      observed. The overestimated plasma profile of propranolol suggests that the low
      bioavailability of propranolol is a result of first-pass metabolism by the
      intestine wall and the liver, because the calculated absolute absorption is
      almost perfect. This proposed model is also suitable for estimation of segmental
      absorption, which is useful for the development of drug delivery systems. We have
      demonstrated that the plasma profile of orally administered drugs can be
      predicted by use of gastrointestinal transit and segmental absorbability
      information and that this method is especially useful for estimating separately
      the effect of absolute absorption and first-pass metabolism on the
      bioavailability of drugs.

PMID- 9232548
TI  - A comparative pharmacokinetic-pharmacodynamic study of the electrocardiographic
      effects of epinastine and terfenadine in rats.
AB  - The effects of epinastine hydrochloride and terfenadine on electrocardiographic
      (ECG) parameters in rats were investigated from a pharmacokinetic and
      pharmacodynamic perspective. Epinastine hydrochloride (1 or 3 mg kg-1 h-1) or
      terfenadine (5, 10 or 15 mg kg-1 h-1) was intravenously infused into rats
      anaesthetized with urethane and alpha-chloralose. The changes in the QT interval
      derived from limb lead II and the chest lead, heart rate and PR interval were
      analysed. The time-course of the plasma drug-concentration of each drug was also
      investigated. Terfenadine prolonged the QT interval in an infusion-rate-dependent
      manner, its EC50 value was 792-1039 ng mL-1. An obvious QT prolongation was,
      moreover, observed even at a plasma terfenadine concentration of 100-200 ng mL-1,
      which is clinically quite high, but might be achieved under a definite condition
      such as a restrained terfenadine metabolism. Terfenadine also induced PR
      prolongation and bradycardia in an infusion-rate dependent manner. Epinastine
      slightly increased the heart rate, but did not affect any of the other ECG
      parameters even at a plasma concentration of 400 ng mL-1, which is more than 10
      times the maximum concentration attained after an ordinary dosage regimen in man.
      We conclude that epinastine might have an advantage over terfenadine in avoiding
      adverse electrocardiographic reactions.

PMID- 9232549
TI  - Fatigue revisited.

PMID- 9232550
TI  - Mechanisms of muscle fatigue in intense exercise.
AB  - The manifestations of fatigue, as observed by reductions in the ability to
      produce a given force or power, are readily apparent soon after the initiation of
      intense activity. Moreover, following the activity, a sustained weakness may
      persist for days or even weeks. The mechanisms responsible for the impairment in
      performance are various, given the severe strain imposed on the multiple organ
      systems, tissues and cells by the activity. At the level of the muscle cell, ATP
      utilization is dramatically accelerated in an attempt to satisfy the energy
      requirements of the major processes involved in excitation and contraction namely
      sarcolemmal Na+/K+ exchange, sarcoplasmic reticulum Ca2+ sequestration and
      actomyosin cycling. In an attempt to maintain ATP levels, high-energy phosphate
      transfer, glycolysis and oxidative phosphorylation are recruited. With intense
      activity, ATP production rates are unable to match ATP utilization rates, and
      reductions in ATP occur accompanied by accumulation of a range of metabolic by
      products such as hydrogen ions, inorganic phosphate, AMP, ADP and IMP. Selective
      by-products are believed to disturb Na+/K+ balance, Ca2+ cycling and actomyosin
      interaction, resulting in fatigue. Cessation of the activity and normalization of
      cellular energy potential results in a rapid recovery of force. This type of
      fatigue is often referred to as metabolic. Repeated bouts of high-intensity
      activity can also result in depletion of the intracellular substrate, glycogen.
      Since glycogen is the fundamental fuel used to sustain both glycolysis and
      oxidative phosphorylation, fatigue is readily apparent as cellular resources are
      exhausted. Intense activity can also result in non-metabolic fatigue and weakness
      as a consequence of disruption in internal structures, mediated by the high force
      levels. This type of impairment is most conspicuous following eccentric muscle
      activity; it is characterized by myofibrillar disorientation and damage to the
      cytoskeletal framework in the absence of any metabolic disturbance. The specific
      mechanisms by which the high force levels promote muscle damage and the degree to
      which the damage can be exacerbated by the metabolic effects of the exercise
      remain uncertain. Given the intense nature of the activity and the need for
      extensive, high-frequency recruitment of muscle fibres and motor units in a range
      of synergistic muscles, there is limited opportunity for compensatory strategies
      to enable performance to be sustained. Increased fatigue resistance would appear
      to depend on carefully planned programmes designed to adapt the excitation and
      contraction processes, the cytoskeleton and the metabolic systems, not only to
      tolerate but also to minimize the changes in the intracellular environment that
      are caused by the intense activity.

PMID- 9232551
TI  - Energetics of high-intensity exercise (soccer) with particular reference to
      fatigue.
AB  - Soccer entails intermittent exercise with bouts of short, intense activity
      punctuating longer periods of low-level, moderate-intensity exercise. High levels
      of blood lactate may sometimes be observed during a match but the active recovery
      periods at submaximal exercise levels allow for its removal on a continual basis.
      While anaerobic efforts are evident in activity with the ball and shadowing fast
      moving opponents, the largest strain is placed on aerobic metabolism. On average,
      competitive soccer corresponds to an energy expenditure of about 75% maximal
      aerobic power. The energy expenditure varies with playing position, being highest
      among midfield players. Muscle glycogen levels can be reduced towards the end of
      a game, the level of reduction being reflected in a decrease in work rate. Blood
      glucose levels are generally well-maintained, although body temperature may rise
      by 2 degrees C even in temperate conditions. The distance covered by players
      tends to under-reflect the energy expended. Unorthodox modes of motion-running
      backwards and sideways, accelerating, decelerating and changing direction
      accentuate the metabolic loading. These are compounded by the extra requirements
      for energy associated with dribbling the ball and contesting possession. The
      overall energy expended is extreme when players are required to play extra-time
      in tournaments. Training, nutritional and tactical strategies may be used to
      reduce the effects of fatigue that may occur late in the game.

PMID- 9232552
TI  - Diet composition and the performance of high-intensity exercise.
AB  - The crucial role of muscle glycogen as a fuel during prolonged exercise is well
      established, and the effects of acute changes in dietary carbohydrate intake on
      muscle glycogen content and on endurance capacity are equally well known. More
      recently, it has been recognized that diet can also affect the performance of
      high-intensity exercise of short (2-7 min) duration. If the muscle glycogen
      content is lowered by prolonged (1-1.5 h) exhausting cycle exercise, and is
      subsequently kept low for 3-4 days by consumption of a diet deficient in
      carbohydrate (< 5% of total energy intake), there is a dramatic (approximately 10
      30%) reduction in exercise capacity during cycling sustainable for about 5 min.
      The same effect is observed if exercise is preceded by 3-4 days on a carbohydrate
      restricted diet or by a 24 h total fast without prior depletion of the muscle
      glycogen. Consumption of a diet high in carbohydrate (70% of total energy intake
      from carbohydrate) for 3-4 days before exercise improves exercise capacity during
      high-intensity exercise, although this effect is less consistent. The blood
      lactate concentration is always lower at the point of fatigue after a diet low in
      carbohydrate and higher after a diet high in carbohydrate than after a normal
      diet. Even when the duration of the exercise task is kept constant, the blood
      lactate concentration is higher after exercise on a diet high in carbohydrate
      than on a diet low in carbohydrate. Consumption of a low-carbohydrate
      isoenergetic diet is achieved by an increased intake of protein and fat. A high
      protein diet, particularly when combined with a low carbohydrate intake, results
      in metabolic acidosis, which ensues within 24 h and persists for at least 4 days.
      This appears to be the result of an increase in the circulating concentrations of
      strong organic acids, particularly free fatty acids and 3-hydroxybutyrate,
      together with an increase in the total plasma protein concentration. This
      acidosis, rather than any decrease in the muscle glycogen content, may be
      responsible for the reduced exercise capacity in high-intensity exercise; this
      may be due to a reduced rate of efflux of lactate and hydrogen ions from the
      working muscles. Alternatively, the accumulation of acetyl groups in the
      carbohydrate-deprived state may reduce substrate flux through the pyruvate
      dehydrogenase complex, thus reducing aerobic energy supply and accelerating the
      onset of fatigue.

PMID- 9232553
TI  - Aetiology of skeletal muscle 'cramps' during exercise: a novel hypothesis.
AB  - The aetiology of exercise-associated muscle cramps (EAMC), defined as 'painful,
      spasmodic, involuntary contractions of skeletal muscle during or immediately
      after physical exercise', has not been well investigated and is therefore not
      well understood. This review focuses on the physiological basis for skeletal
      muscle relaxation, a historical perspective and analysis of the commonly
      postulated causes of EAMC, and known facts about EAMC from recent clinical
      studies. Historically, the causes of EAMC have been proposed as (1) inherited
      abnormalities of substrate metabolism ('metabolic theory') (2) abnormalities of
      fluid balance ('dehydration theory'), (3) abnormalities of serum electrolyte
      concentrations ('electrolyte theory') and (4) extreme environmental conditions of
      heat or cold ('environmental theory'). Detailed analyses of the available
      scientific literature including data from recent studies do not support these
      hypothesis for the causes of EAMC. In a recent study, electromyographic (EMG)
      data obtained from runners during EAMC revealed that baseline activity is
      increased (between spasms of cramping) and that a reduction in the baseline EMG
      activity correlates well with clinical recovery. Furthermore, during acute EAMC
      the EMG activity is high, and passive stretching is effective in reducing EMG
      activity. This relieves the cramp probably by invoking the inverse stretch
      reflex. In two animal studies, abnormal reflex activity of the muscle spindle
      (increased activity) and the Golgi tendon organ (decreased activity) has been
      observed in fatigued muscle. We hypothesize that EAMC is caused by sustained
      abnormal spinal reflex activity which appears to be secondary to muscle fatigue.
      Local muscle fatigue is therefore responsible for increased muscle spindle
      afferent and decreased Golgi tendon organ afferent activity. Muscles which cross
      two joints can more easily be placed in shortened positions during exercise and
      would therefore decrease the Golgi tendon organ afferent activity. In addition,
      sustained abnormal reflex activity would explain increased baseline EMG activity
      between acute bouts of cramping. Finally, passive stretching invokes afferent
      activity from the Golgi tendon organ, thereby relieving the cramp and decreasing
      EMG activity.

PMID- 9232554
TI  - Fluid balance during team sports.
AB  - Sweat losses during team sports are influenced by the intermittent nature of the
      work rates (high-intensity exercise interspersed with low-level activity and both
      formal and informal rest periods), and a high level of inter- and intra
      individual variability in workloads. Since many team sports have evolved in
      countries with cool climates, traditions and rules governing the time of play,
      duration of play without a break, and the type of uniforms may lead to
      inappropriately high thermal stresses when these sports are played in hot
      environments (i.e. > 25 degrees C, 60% relative humidity). Fluid intake during
      team sports is largely determined by opportunities to drink during formal rest
      periods and during informal stoppages in play. Present regulations concerning
      fluid breaks in some sports may be inappropriate if fluid requirements of players
      competing in hot environments are to be met to prevent hypohydration and fatigue.
      Nevertheless, it appears that in most team sports, there are adequate
      opportunities for players to keep fluid deficits below 2% of body mass. Studies
      across a number of sports show that mean fluid intakes of up to 1000 ml h-1 can
      be achieved. Strategies are required to help team sport players realize the
      importance of optimal hydration, and to use or create opportunities within their
      sport to maximize fluid intake. Guidelines for hydration during training and
      competition are suggested with the proviso that these should be adapted for each
      individual and his or her own sport.

PMID- 9232555
TI  - Recovery from prolonged exercise: restoration of water and electrolyte balance.
AB  - Rapid and complete restoration of fluid balance after exercise is an important
      part of the recovery process, especially in hot, humid conditions, when sweat
      losses may be high. Rehydration after exercise can only be achieved if the
      electrolytes lost in sweat, as well as the lost water, are replaced. However, the
      amount of electrolytes lost in sweat is highly variable between individuals and
      although the optimum drink may be achieved by matching drink electrolyte intake
      with sweat electrolyte loss, this is virtually impossible in sport settings. The
      composition of sweat varies considerably not only between individuals, but also
      with time during exercise and it is further influenced by the state of
      acclimatization. A moderate excess of salt intake would appear to be beneficial
      as far as hydration status is concerned, without any detrimental effects on
      health, provided that fluid intake is in excess of sweat loss and the renal
      function is not impaired. To achieve effective rehydration following exercise in
      the heat, the rehydration beverage should contain moderately high levels of
      sodium (at least 50 mmol l-1), and possibly also some potassium. The addition of
      substrate is not necessary for rehydration, although a small amount of
      carbohydrate (< 2%) may improve the rate of intestinal uptake of sodium and
      water. The volume of beverage consumed should be greater than the volume of sweat
      lost to provide for the ongoing obligatory urine losses. Therefore, the
      palatability of the beverage is important. Many individuals may lose substantial
      amounts of sweat and will therefore have to consume large amounts of replacement
      fluids and this is more likely to be achieved if the taste is perceived as being
      pleasant. Water alone is adequate for rehydration purposes when solid food is
      consumed, as this replaces the electrolytes lost in sweat. However, there are
      many situations where intake of solid food is not possible or is deliberately
      avoided and, in these instances, the inclusion of electrolytes in rehydration
      beverages is essential. Where a second exercise bout has to be performed,
      replacement of sweat losses is an essential part of the recovery process.
      Exercise performance will be impaired if complete rehydration is not achieved.

PMID- 9232556
TI  - Nutritional strategies to minimize fatigue during prolonged exercise: fluid,
      electrolyte and energy replacement.
AB  - While the presence of palatable (20 mmol l-1) concentrations of NaCl in drinks
      containing carbohydrate consumed during intense exercise would not be expected to
      promote absorption or significantly help maintain fluid balance, there is no
      doubt that athletes should ingest some from of carbohydrate (other than fructose)
      during moderate-intensity exercise lasting > 90 min. As only approximately 20 g
      of ingested carbohydrate is oxidized in the first hour of exercise, athletes
      should probably consume 100 ml every 10 min of a dilute (3-5 g 100 ml-1)
      carbohydrate solution and thereafter increase the carbohydrate concentration to
      approximately 10 g 100 ml-1 to match the peak (approximately 1 g min-1) rates of
      plasma glucose oxidation. Drinking more than those amounts of carbohydrate may
      increase muscle glycogen oxidation by attenuating the fall in plasma insulin
      concentration and thereby delaying fat mobilization, especially at relatively low
      (55% of peak oxygen consumption) intensity exercise. As carbohydrate ingestion
      does not slow the rate of glycogen utilization in working muscle, it is also
      advisable for endurance athletes to start exercise with an adequate supply of
      muscle glycogen, irrespective of whether or not they ingest carbohydrate during
      exercise. While carbohydrate ingestion 'spares' conversion of liver glycogen to
      plasma glucose and prevents hypoglycemia, it does not delay the fatigue
      associated with a low (approximately 20 mmol kg-1) glycogen content in working
      muscle. Conversely, increases in glycogen content of working muscle at the start
      of exercise have no effect on the rates of plasma glucose oxidation. Higher
      initial rates of glycogen utilization by active muscles in 'carbohydrate-loaded'
      subjects decrease the indirect oxidation (via lactate) of non-working muscle
      glycogen, rather than the conversion of liver glycogen to plasma glucose. Hence,
      athletes should ingest carbohydrate during endurance exercise even if they have
      'carbohydrate-loaded' before exercise.

PMID- 9232557
TI  - Nutritional strategies for promoting fat utilization and delaying the onset of
      fatigue during prolonged exercise.
AB  - Carbohydrate ingestion before and during endurance exercise delays the onset of
      fatigue (reduced power output). Therefore, endurance athletes are recommended to
      ingest diets high in carbohydrate (70% of total energy) during competition and
      training. However, increasing the availability of plasma free fatty acids has
      been shown to slow the rate of muscle and liver glycogen depletion by promoting
      the utilization of fat. Ingested fat, in the form of long-chain (C16-22)
      triacylglycerols, is largely unavailable during acute exercise, but medium-chain
      (C8-10) triacylglycerols are rapidly absorbed and oxidized. We have shown that
      the ingestion of medium-chain triacylglycerols in combination with carbohydrate
      spares muscle carbohydrate stores during 2 h of submaximal (< 70% VO2 peak)
      cycling exercise, and improves 40 km time-trial performance. These data suggest
      that by combining carbohydrate and medium-chain triacylglycerols as a pre
      exercise supplement and as a nutritional supplement during exercise, fat
      oxidation will be enhanced, and endogenous carbohydrate will be spared. We have
      also examined the chronic metabolic adaptations and effects on substrate
      utilization and endurance performance when athletes ingest a diet that is high in
      fat (> 70% by energy). Dietary fat adaptation for a period of at least 2-4 weeks
      has resulted in a nearly two-fold increase in resistance to fatigue during
      prolonged, low- to moderate-intensity cycling (< 70% VO2 peak). Moreover,
      preliminary studies suggest that mean cycling 20 km time-trial performance
      following prolonged submaximal exercise is enhanced by 80 s after dietary fat
      adaptation and 3 days of carbohydrate loading. Thus the relative contribution of
      fuel substrate to prolonged endurance activity may be modified by training, pre
      exercise feeding, habitual diet, or by artificially altering the hormonal milieu
      or the availability of circulating fuels. The time course and dose-response of
      these effects on maximizing the oxidative contribution of fat for exercise
      metabolism and in exercise performance have not been systematically studied
      during moderate- to high-intensity exercise in humans.

PMID- 9232558
TI  - Training techniques to improve fatigue resistance and enhance endurance
      performance.
AB  - Despite their best efforts, sports scientists have found it difficult to persuade
      elite athletes to experiment with their training regimens. Thus, until recently,
      exercise physiologists have had limited impact on the training practices of
      successful athletes, with most of the innovations in the training patterns of the
      best athletes coming from the empirical observations of top-level coaches. One
      form of training recognized by sports scientists and used by athletes for several
      decades in interval/transition training. Such training consists of a number of
      exercise bouts alternated with short rest intervals of more slowly paced activity
      and is thought to improve the fatigue resistance of the active muscles by
      exposing them to sustained, high-intensity exercise at the athlete's maximal
      steady-state pace. Few scientific studies, however, have examined the effects of
      transition training on the performances of competitive athletes. This paper
      identifies the physiological factors associated with successful endurance
      performance, and summarizes the results of investigations on competitive
      endurance cyclists which examined the time-course of changes in performance in
      response to a sustained, high-intensity interval training programme.

PMID- 9232559
TI  - Modeling training and overtraining.
AB  - This paper adapts the dose-response research tool, well established in
      pharmacological studies, to an exercise and performance setting. Training is
      measured in quantitative units as the dosage inputs, and their effects on
      fitness, fatigue, overtraining and performance responses are modelled. In this
      way, one can answer such questions as 'what performance level would be predicted
      if a certain amount of training was undertaken?' More specifically, athletes and
      their coaches are interested in designing a training schedule to maximize
      performance potential at some future date and minimize the risk of overtraining
      during that time, for some minimal training inputs. This approach leads to the
      practical recommendation that athletes should train more intensely but only on
      alternate days, for a 5 month session, in a triangular-shaped training profile,
      with the heaviest training occurring between weeks 12 and 4 before competition.

PMID- 9232560
TI  - The 'worn-out athlete': a clinical approach to chronic fatigue in athletes.
AB  - Chronic fatigue in the athletic population is a common but difficult diagnostic
      challenge for the sports physician. While a degree of fatigue may be normal for
      any athlete during periods of high-volume training, the clinician must be able to
      differentiate between this physiological fatigue and more prolonged, severe
      fatigue which may be due to a pathological condition. As chronic fatigue can be
      the presenting symptom of many curable and harmful diseases, medical conditions
      which cause chronic fatigue have to be excluded. The clinician must then be able
      to differentiate between chronic fatigue associated with training or chronic
      fatigue from other medical causes, and also between the chronic fatigue syndrome
      and the overtraining syndrome. Once the clinician has excluded all of the above
      medical conditions which cause chronic fatigue in athletes, a significant
      proportion of fatigued athletes remain without a diagnosis. Novel data indicate
      that skeletal muscle disorders may play a role in the development of symptoms
      experienced by the athlete with chronic fatigue. The histological findings from
      muscle biopsies of athletes suffering from the 'fatigued athlete myopathic
      syndrome' are presented. We have designed a clinical approach to the diagnosis
      and work-up of the athlete presenting with chronic fatigue. The strength of this
      approach is that it hinges on the participation of a multidisciplinary team in
      the diagnosis and management of the athlete with chronic fatigue. The athlete,
      coach, dietician, exercise physiologist and sport psychologist all play an
      important role in enabling the physician to make the correct diagnosis.

PMID- 9232561
TI  - Oxidants, antioxidant nutrients and the athlete.
AB  - Strenuous physical exercise induces oxidative stress. There may be a number of
      sources of this oxidative stress, including mitochondrial superoxide production,
      ischaemia-reperfusion mechanisms and auto-oxidation of catecholamines. Severe or
      prolonged exercise can overwhelm antioxidant defences, which include vitamins E
      and C and thiol antioxidants, which are interlinked in an antioxidant network, as
      well as antioxidant enzymes. Evidence for oxidative stress and damage during
      exercise comes from direct measurement of free radicals, from measurement of
      damage to lipids and DNA, and from measurement of antioxidant redox status,
      especially glutathione. There is little evidence that antioxidant supplementation
      can improve performance, but a large body of work suggests that bolstering
      antioxidant defences may ameliorate exercise-induced damage, suggesting that the
      benefits of antioxidant intervention may be for the long term rather than the
      short term.

PMID- 9232562
TI  - Travel fatigue and jet-lag.
AB  - Travel across multiple time zones is a common feature of the lifestyle of
      contemporary international sport competitors. This entails a disruption of the
      body's circadian timing mechanisms. Symptoms of 'jet-lag' persist until circadian
      rhythms re-tune into local time. Exercise performance may be impaired during the
      period of adjustment to the new time zone. Behavioural and pharmacological
      strategies are available to help accelerate the resynchronization of circadian
      rhythms. It is recommended that sports administrators should consider the
      consequences of jet-lag and the time needed to overcome it when planning the
      international itineraries of travelling athletes.

PMID- 9232563
TI  - 1997 Charles T. Dotter Lecture. Will interventional radiology survive into the
      next millennium? Absolutely! Unequivocally! Definitely! .... I think so.

PMID- 9232564
TI  - Transrectal and transvaginal abscess drainage.
AB  - The TR and TV approaches to deep pelvic abscesses have been made safe and easy by
      improvements in endoluminal US technology. Most procedures take well under an
      hour, and standard intravenous sedation is usually sufficient for patient
      comfort. The simplest and safest technique employs a combination of endoluminal
      US, with biopsy guides for precision needle advancement, and fluoroscopy for
      dilating the tract and placing a drainage catheter. Patient acceptance of TR and
      TV catheters is high, and resolution can typically be expected within 3-5 days.
      In the majority of cases, catheter treatment, combined with antibiotic therapy,
      is curative.

PMID- 9232565
TI  - Preliminary experience with uterine artery embolization for uterine fibroids.
AB  - PURPOSE: To evaluate the potential usefulness of transcatheter uterine artery
      embolization as a treatment for fibroid-related vaginal bleeding and pelvic pain
      refractory to hormonal therapy and myomectomy. MATERIALS AND METHODS: Eleven
      patients (aged 27-55 years; mean, 44.2 years; none desiring future pregnancy)
      with refractory vaginal bleeding and/or chronic pelvic pain related to uterine
      leiomyomata underwent uterine artery embolization with use of polyvinyl alcohol
      (PVA) particles. Clinical improvement was assessed by detailed questionnaire at 2
      9 months (mean, 5.8 months) after the procedure. Sonographic measurements of the
      uterus and dominant masses were obtained before and at 2 months after the
      procedure. RESULTS: All 11 patients underwent technically successful
      embolization. Eight of nine women who completed the follow-up questionnaire
      reported noticeable symptomatic improvement, including three women with complete
      resolution of symptoms. One woman (the only patient undergoing unilateral
      embolization) exhibited no clinical response. Another patient developed
      endometritis and pyometra 3 weeks after the procedure, necessitating
      hysterectomy. Large reductions in uterine volume (average, 40%) and dominant
      fibroid size (average, 60%-65%) were sonographically demonstrated. CONCLUSION:
      Uterine artery embolization represents a promising new method of treating fibroid
      related menorrhagia and pelvic pain. Further investigation will be required to
      assess clinical response and durability, identify appropriate candidates, and
      define the optimal angiographic technique and PVA particle size.

PMID- 9232566
TI  - Percutaneous transcatheter renal ablation with absolute ethanol for uncontrolled
      hypertension or nephrotic syndrome: results in 11 patients with end-stage renal
      disease.
AB  - PURPOSE: Retrospective review of authors' experience with percutaneous
      transcatheter renal ablation in patients with uncontrolled hypertension and/or
      nephrotic syndrome. MATERIALS AND METHODS: Between April 1987 and September 1995,
      renal ablation was performed on 11 patients aged 10 months to 21 years. All
      patients had end-stage renal disease (ESRD) with uncontrolled hypertension (10
      patients) and/or nephrotic syndrome (four patients). Uncontrolled hypertension
      was defined as diastolic pressure greater than 90 mm Hg despite multidrug
      antihypertensive therapy. Nephrotic syndrome was defined as proteinuria exceeding
      960 mg/m2 per day, serum albumin level less than 3 g/dL, and generalized edema.
      Embolization was performed with absolute ethanol from a common femoral artery
      approach. In most cases, a balloon catheter was used to prevent alcohol reflux
      into the aorta or nontarget renal artery branches, such as the adrenal arteries.
      Angiographic stasis of contrast material in the renal arteries was the endpoint.
      RESULTS: All patients experienced a postembolization syndrome of 3-5 days
      duration, clinically manifested by variable degrees of nausea, vomiting, fever,
      and pain. Long-term improvement in hypertension was observed in nine patients.
      Improvement in hypertension was defined as diastolic blood pressure below 90 mm
      Hg while the patient received the same or fewer antihypertensive medications. The
      four patients with nephrotic syndrome were cured of their proteinuria and edema.
      CONCLUSIONS: Transarterial renal ablation with alcohol is efficacious for
      treatment of uncontrolled hypertension and nephrotic syndrome in patients with
      ESRD. The morbidity and mortality in our series were less than those reported for
      surgical nephrectomy.

PMID- 9232567
TI  - Anastomoses in recurrent epistaxis.

PMID- 9232568
TI  - Stent-grafts for revision of TIPS stenoses and occlusions: a clinical pilot
      study.
AB  - PURPOSE: To assess the clinical and technical results of stent-graft placement
      for revision of transjugular intrahepatic portosystemic shunt (TIPS) stenoses and
      occlusions. MATERIALS AND METHODS: Six patients who developed recurrent TIPS
      stenosis or occlusion of the parenchymal tract underwent shunt revision with use
      of polytetrafluoroethylene (PTFE) stent-grafts anchored at both ends by Z stents
      and centrally supported by Wallstents. RESULTS: Before graft placement, mean
      primary patency was 50 days (range, 9-100 days). Patients underwent one to eight
      revisions with angioplasty or stent placement (mean, 3.2). Three patients had
      biliary-TIPS fistulas documented with use of a prototype double occlusion balloon
      catheter. Stent-grafts were successfully placed within the obstructed shunt,
      creating an excellent lumen in all cases. The portosystemic gradient was
      decreased from a mean of 24.3 mm Hg (range, 12-35 mm Hg) to a mean of 10.3 mm Hg
      (range, 7-16 mm Hg). Five of six patients were asymptomatic and no complications
      occurred (median clinical follow-up, 331 days). One patient died of pre-existing
      multi-organ system failure. The duration of primary patency after stent-grafting
      was improved (mean, 229 days; range, 27-324 days) and the difference approached
      statistical significance despite the small sample size (P = .056, paired t test).
      Three patients remained primarily patent at a mean venographic follow-up of 315
      days. One shunt occluded at 1 month from residual thrombus in the portal vein,
      and one stenosis occurred that was secondary to misplacement of the original
      stent-graft. Patency was re-established in each of these patients. CONCLUSION:
      PTFE covered stent-grafts are effective for shunt revision in patients with tract
      stenosis or occlusion and appear to improve TIPS patency.

PMID- 9232569
TI  - Sonography of transjugular intrahepatic portosystemic shunts: detection of
      elevated portosystemic gradients and loss of shunt function.
AB  - PURPOSE: To evaluate the role of ultrasound (US) in the detection of elevated
      portosystemic gradients and loss of shunt function in patients with a
      transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: The
      authors' prospectively compared 151 Doppler hepatic sonograms with follow-up
      portal venograms in 64 patients with TIPS. Sonographic data from within the
      portal system, hepatic arteries, and three areas within the TIPS were collected.
      Statistical analysis of these parameters was used to establish the US criteria
      for shunt dysfunction. RESULTS: Midshunt velocity thresholds of less than 50 and
      less than 60 cm/sec yielded sensitivities and specificities of 46% and 93%, and
      57% and 89%, respectively, for the detection of portosystemic gradients exceeding
      15 mm Hg. Use of a threshold midshunt velocity of less than 60 cm/sec or main
      portal vein velocity of less than 40 cm/sec raised the shunt dysfunction
      detection sensitivity to 86%, with a specificity of 54%. CONCLUSION: Doppler US
      is an effective noninvasive screening tool for detecting elevated portosystemic
      gradients and evaluating the functional status of a TIPS. Midshunt velocities of
      less than 60 cm/sec or main portal vein velocities less than 40 cm/sec are a
      useful threshold for detecting shunt dysfunction.

PMID- 9232570
TI  - Incidence and management of arterial emboli from hemodialysis graft surgical
      thrombectomy.
AB  - PURPOSE: To determine the incidence and significance of arterial emboli resulting
      from surgical thrombectomy/revision of hemodialysis grafts. This information may
      help in determining the significance and management of similar emboli resulting
      from percutaneous hemodialysis graft thrombolysis. PATIENTS AND METHODS: Patients
      undergoing surgical thrombectomy/revision of clotted hemodialysis grafts are
      studied with postoperative fistulography per institutional protocol whenever
      possible. For this retrospective study, all postoperative fistulograms from a 1
      year period were reviewed for the presence of arterial emboli. Patients with
      documented arterial emboli were examined for evidence of hand/digital ischemia;
      only those patients with signs or symptoms of ischemia were treated. At clinical
      follow-up, repeated evaluation for hand/digital ischemia was performed. RESULTS:
      Ninety-one thrombectomy/revision procedures were performed during the study
      period. Postoperative fistulograms were obtained after 67 of these procedures in
      32 patients. One patient complained of hand pain during dialysis prior to
      acquisition of the postoperative fistulogram. Arterial emboli were documented in
      eight patients (12%; brachial, n = 3; radial, n = 2; ulnar, n = 2; radial/ulnar,
      n = 1). The single symptomatic brachial embolus was percutaneously removed; no
      intervention was undertaken in the remainder. At mean follow-up of 14 months, no
      patient had developed hand or digital ischemia. Subsequent fistulograms
      demonstrated partial (n = 2) or complete (n = 2) resolution of the untreated
      emboli. CONCLUSION: Arterial emboli are a relatively common occurrence with
      surgical thrombectomy/revision. Conservative management appears to be indicated
      in asymptomatic patients.

PMID- 9232571
TI  - Mechanical declotting of thrombosed dialysis grafts: experience in 86 cases.
AB  - PURPOSE: To evaluate the efficacy, safety, and primary patency of percutaneous
      mechanical declotting of thrombosed dialysis grafts using latex balloons.
      MATERIALS AND METHODS: Fifty-nine patients with 86 episodes of dialysis graft
      thrombosis underwent percutaneous mechanical declotting with balloons using
      crossing catheter or transjugular technique. Vital signs, peripheral oxygenation,
      technical success, procedure time, and complications were recorded prospectively.
      Technical success was defined as a patent graft at the completion of the
      procedure. Clinical success, defined as successful dialysis for 1 week, and
      primary patency were obtained retrospectively from review of the dialysis
      records. RESULTS: Technical success was achieved in 74 of 86 procedures (86%).
      Median procedure time was 115 minutes, including failed cases. Ten of the 12
      technical failures were due to resistant vascular stenoses precluding graft
      patency, despite removal of thrombus. There were no immediate complications. One
      patient died of sepsis 4 days after declotting. Clinical success was achieved
      after 65 of 86 procedures (76%); nine grafts thrombosed within 1 week of a
      technically successful declotting procedure. Primary patency (including technical
      failures) was 37% at 3 months, 31% at 6 months, and 17% at 12 months. CONCLUSION:
      Mechanical declotting is an effective means of restoring patency to thrombosed
      dialysis grafts.

PMID- 9232572
TI  - Flow characteristics of peripherally inserted central catheters.
AB  - PURPOSE: Clinical applications of peripherally inserted central catheters (PICCs)
      are limited by the relatively small lumina and long lengths of these devices.
      Quantitative analysis of the flow capabilities of a variety of PICCs was
      performed to aid in deciding which patients should have a PICC and in selecting
      the appropriate catheter. MATERIALS AND METHODS: Sixteen different PICCs from six
      manufacturers were infused at flow rates of 25-270 mL/h. Infusions were performed
      with distilled water, normal saline, total parenteral nutrition solution,
      intralipids, and blood. Flow versus pressure curves were generated for each PICC
      and infusate. Additional catheter data recorded included the working length,
      outer diameter (OD), and inner diameter (ID) of the PICCs. RESULTS: Because of
      the thin wall construction of polyurethane catheters, PICCs made from
      polyurethane showed much better flow rates than silicone PICCs of a comparable
      OD. The measured ODs of the PICCs were 4-6 F, whereas the IDs ranged from 0.012
      to 0.032 inch. Because of the small ID of some PICCs, infusing blood or
      intralipids is not practical. CONCLUSION: There is significant variability in the
      flow capabilities of available PICCs. Many of the PICCs require pressures greater
      than those that can be generated by commercially available infusion pumps.
      Matching PICC characteristics to the desired application will avoid many of the
      clinical problems currently encountered with PICCs.

PMID- 9232574
TI  - Acute Budd-Chiari syndrome caused by percutaneous placement of a transhepatic
      inferior vena cava catheter.

PMID- 9232573
TI  - Image-guided insertion of the Uldall tunneled hemodialysis catheter: technical
      success and clinical follow-up.
AB  - PURPOSE: To evaluate the technical success, complication rates, and survival time
      of the Uldall double-lumen catheter placed by interventional radiologists in
      patients presenting to a hemodialysis clinic. MATERIALS AND METHODS: Patients
      eligible for this study included those with end-stage renal disease (ESRD) who
      had failed peripheral vascular access or who were awaiting access at a
      hemodialysis unit between June 1993 and March 1996. All catheters were placed
      under fluoroscopic and ultrasound guidance in the angiography suite. RESULTS:
      Attempts were made to insert 130 catheters into jugular veins in a consecutive
      series of 61 patients with ESRD. The accumulated catheter experience in this
      cohort was 15,380 days and the median survival time was 141 days (95% confidence
      interval [CI]; 116 days-166 days). One hundred twenty-one catheters (93%) were
      successfully inserted, mainly (94%) into the internal jugular vein. Excellent
      dialysis blood flow rate was obtained-on average 365 mL/min (95% CI; 350-379
      mL/min). The overall infection rate, including exit site (n = 13), sepsis (n =
      19), and clavicular osteomyelitis (n = 1), was 2.1 episodes per 1,000 catheter
      days. CONCLUSIONS: This catheter is recommended for acute and longer term
      hemodialysis for patients without peripheral vascular access. It can be inserted
      percutaneously, the same internal jugular vein can be used repeatedly with few
      complications and good blood flow, and the technique can be easily learned by any
      experienced angiographer.

PMID- 9232576
TI  - Obtaining arterial access in trauma patients.

PMID- 9232575
TI  - Management of port infections.

PMID- 9232577
TI  - Placement of endothelial cells on the luminal surface of denuded arteries in
      vitro and in vivo.
AB  - PURPOSE: Experiments were performed to determine if the percutaneous placement of
      endothelial cells on denuded arterial surfaces is feasible. MATERIALS AND
      METHODS: For in vitro adhesion assays, rabbit microvascular endothelial cells
      were stained with a fluorescent marker and placed on the luminal surface of disks
      of denuded rabbit aorta. At varying times thereafter, the nonadherent cells were
      removed, and the adherent cells were quantitated with use of fluorescence
      microscopy. For in vivo studies, angioplasty was performed on external iliac
      arteries in five rabbits, and a double-balloon catheter, positioned at the
      dilatation site, was used to deliver fluorescent rabbit microvascular endothelial
      cells. Ten minutes (n = 2), 1 hour (n = 2), 1 day (n = 1), or 3 days (n = 1)
      after cell placement, the number of fluorescent cells remaining on each artery
      was determined. RESULTS: In vitro rabbit microvascular endothelial cell
      attachment was (a) serum-dependent, peaking with media containing 25% autologous
      serum; (b) time-dependent, peaking at 30 minutes; and (c) cell density-dependent.
      In vivo rabbit microvascular endothelial cell attachment was (a)
      noncircumferential, (b) appeared to be gravity-dependent, and (c) appeared
      unchanged over 3 days with respect to number of cells per cross-section and
      length of artery having endothelium. CONCLUSIONS: Percutaneous delivery of
      endothelial cells onto denuded arterial surfaces with use of optimal conditions
      is feasible and these cells remain adherent for at least 3 days.

PMID- 9232578
TI  - The dissected aorta: percutaneous treatment of ischemic complications--principles
      and results.
AB  - PURPOSE: Describe the principles and results of percutaneous treatment of
      ischemic complications of aortic dissection. MATERIALS AND METHODS: Twenty-four
      patients with aortic dissection complicated by ischemic compromise of the liver
      or bowel (n = 15), kidney (n = 18), or lower extremity (n = 13) were evaluated by
      means of aortography, intravascular ultrasound, and manometry, and were treated
      percutaneously. Visceral arteries were classified as obstructed or nonobstructed.
      Obstruction was classified as static, in which the dissecting hematoma extended
      into and narrowed the lumen of a branch artery, or dynamic, in which the
      dissection flap prolapsed into the vessel origin or narrowed the true lumen (TL)
      above it. Treatment consisted of vascular stents alone (n = 4), or balloon
      fenestration (n = 20) without (n = 8) or with (n = 12) vascular stents. RESULTS:
      Obstruction was present in 77 arteries and was static in 12 arteries, dynamic in
      45 arteries, static and dynamic in 17 arteries, and indeterminate in three
      arteries. Percutaneous treatment did not alter false lumen (FL) pressure, but
      reduced the peak systolic interluminal pressure gradient from 28 mm Hg to 2 mm Hg
      and restored flow in 71 of 77 arteries (92%). Six patients died within 30 days
      (25% operative mortality), none as a result of the procedure. Two additional
      patients died in follow-up from complications of an expanding FL. Technical
      complications in two patients due to altered hemodynamics after initial
      intervention were recognized and corrected percutaneously during the same
      procedure. CONCLUSIONS: Percutaneous fenestration and endovascular stent
      deployment are indicated to restore blood flow to arteries compromised by aortic
      dissection. The prognosis of patients is related to the ischemic injury sustained
      prior to the percutaneous interventional procedure and, in patients with acute
      type I dissection who have not undergone surgery, to the preoperative stability
      of the FL.

PMID- 9232579
TI  - Prolonged dilation improves an unsatisfactory primary result of femoropopliteal
      artery angioplasty: usefulness of a perfusion balloon catheter.

PMID- 9232580
TI  - Use of a curved needle for true lumen re-entry during subintimal iliac artery
      revascularization.

PMID- 9232581
TI  - Percutaneous treatment of a collapsed stent-graft.

PMID- 9232582
TI  - Covered gianturco stents for malignant biliary obstruction: preliminary clinical
      evaluation.
AB  - PURPOSE: To evaluate the effectiveness of covered Gianturco stents in patients
      with malignant biliary obstruction. MATERIALS AND METHODS: Three types of
      partially polyurethane-covered stents were implanted in 19 patients with
      malignant biliary obstruction located distal to the hilar confluence. A
      transhepatic approach was employed in all but one patient, in whom the stent was
      placed through a T-tube tract. RESULTS: Stent placement was possible in all
      patients. In 15 patients, the implanted stents were expanded to a mean of 81% of
      their original diameter. In the remaining four patients, the stents expanded to
      less than 40% of the original diameter, and balloon dilation and additional bare
      stent placement were required. All patients except one, who had impairment of
      liver function due to multiple liver metastases, showed relief of jaundice after
      stent placement. At follow-up, which ranged from 5 to 57 weeks (mean, 24.7
      weeks), one stent (5%) was occluded after 26 weeks due to tumor growth above the
      upper stent edge, and required secondary intervention. Complications in three
      patients included stent migration in one (5%) and cholangitis in two (11%).
      CONCLUSION: Preliminary results suggest that placement of covered Gianturco
      stents is feasible, the complication rate is acceptable, and short-term patency
      appears promising.

PMID- 9232583
TI  - Update on the use of percutaneous nephrostomy/balloon dilation for the treatment
      of renal transplant leak/obstruction.
AB  - PURPOSE: Retrospective evaluation of the efficacy of percutaneous nephrostomy and
      nephroureteral stent placement for treatment of post-transplant ureteral leak,
      and percutaneous nephrostomy and balloon dilation for treatment of post
      transplant ureteral obstruction. PATIENTS AND METHODS: Data were reviewed for all
      patients who underwent percutaneous therapy for complications after renal
      transplantation between January 1985 and June 1995. A total of 61 patients with
      complications (leak, n = 17; obstruction, n = 44) had been treated. Patients
      underwent percutaneous nephrostomy followed by antegrade placement of a
      nephroureteral stent. In addition, all patients with obstruction also underwent
      ureteral balloon dilation. Follow-up ranged from 9 weeks to 24 months. Positive
      outcome was defined as nonsurgical closure of leak, significant improvement in
      renal function, and removal of the nephroureteral stent with maintenance of
      stable renal function. RESULTS: Regarding ureteral leak, 10 of 17 patients (59%)
      healed after treatment. Seven patients (41%) did not respond and went on to
      surgical repair. All patients with early (n = 13) ureteral obstruction (< 3
      months after transplantation), had improved renal function (P < .025). Sixty-two
      percent of patients with early obstruction were cured (tube out with stable renal
      function) and 38% went to surgery for ureteral repair. In patients with late (n =
      31) obstruction (> 3 months after transplantation), renal function improved in
      only 58% (P < .01). Only 16% of patients with late obstruction were cured (tube
      out with stable renal function). Ureteral obstruction was persistent in the
      remaining patients and did not respond to multiple balloon dilations. All
      complications were minor and included 23 of 61 (38%) patients with urinary tract
      infections and nine of 61 (14%) patients with limited hematuria. CONCLUSION:
      Percutaneous nephrostomy is very effective in improving renal function in
      patients with early obstruction. It is moderately successful in treating ureteral
      leak. Ureteral balloon dilatation is moderately effective for treatment of
      obstruction in the early (< 3 months) postoperative period. However, balloon
      dilation is minimally successful in curing ureteric obstruction occurring more
      than 3 months after transplantation.

PMID- 9232584
TI  - Permanent ureteral occlusion with use of liquid polyacrylonitrile.

PMID- 9232585
TI  - Transhepatic transduodenal drainage of a pancreatic pseudocyst.

PMID- 9232586
TI  - Incorporation of digital images into an interventional radiology procedure note.

PMID- 9232587
TI  - Guidelines regarding HIV and other bloodborne pathogens in
      vascular/interventional radiology. SCVIR Technology Assessment Committee.

PMID- 9232588
TI  - Quality improvement guidelines for percutaneous transhepatic cholangiography and
      biliary drainage. Society of Cardiovascular and Interventional Radiology.

PMID- 9232589
TI  - Does cervical spinal cord injury induce a higher incidence of complications after
      prophylactic Greenfield filter usage?

PMID- 9232590
TI  - Use of intravenous digital subtraction angiography for imaging of the thoracic
      aorta.

PMID- 9232591
TI  - Cardiovascular and interventional technologists: their growing role in the
      interventional suite.

PMID- 9232592
TI  - Patterning the expression of a tissue-specific transcription factor in
      embryogenesis: HNF1 alpha gene activation during Xenopus development.
AB  - Tissue-specific transcription factors play an essential role in establishing cell
      identity during development. We review our knowledge of the molecular events
      involved in the activation of the gene encoding the tissue-specific transcription
      factor HNF1 alpha (LFB1). The available data suggest that the maternal factors OZ
      1, HNF4 alpha and HNF4 beta act as initial activators of the HNF1 alpha promoter.
      We present evidence suggesting that the mesoderm-inducing factor activin A plays
      a critical role by acting through the HNF4 binding site of the HNF1 alpha
      promoter. The activity of this embryonic morphogen seems to form a gradient
      opposing the distribution of the maternal HNF4 proteins that are concentrated at
      the animal pole of the egg. After zygotic gene transcription the HNF1 alpha
      related transcription factor HNF1 beta accumulates faster than HNF1 alpha itself
      and thus is likely to contribute to the activation of the HNF1 alpha
      transcription via the HNF1 binding site. The cofactor of the HNF1 proteins (DCoH)
      is present throughout development and thus cannot limit the activation potential
      of HNF1 alpha in early development. Our results provide a detailed description of
      setting up the expression pattern of a tissue-specific transcription factor
      during embryogenesis.

PMID- 9232593
TI  - The Drosophila don juan (dj) gene encodes a novel sperm specific protein
      component characterized by an unusual domain of a repetitive amino acid motif.
AB  - We identified and characterized the don juan gene (dj) of Drosophila
      melanogaster. The don juan gene codes for a sperm specific protein component with
      an unusual repetitive six amino acid motif (DPCKKK) in the carboxy-terminal part
      of the protein. The expression of Don Juan is limited to male germ cells where
      transcription of the dj gene is initiated during meiotic prophase. But Western
      blot experiments indicate that DJ protein occurs just postmeiotically.
      Examination of transgenic flies bearing a dj-promoter-lacZ reporter construct
      revealed lacZ mRNA distribution resembling the expression pattern of the
      endogenous dj mRNA in the adult testes, whereas beta-galactosidase expression is
      exclusively present in postmeiotic germ cells. Thus, these observations strongly
      suggest that dj transcripts are under translational repression until in
      spermiogenesis. To study the function and subcellular distribution of DJ in
      spermiogenesis we expressed a chimaeric dj-GFP fusion gene in the male germline
      exhibiting strong GFP fluorescence in the liver testes, where only elongated
      spermatids are decorated. With regard to the characteristic expression pattern of
      DJ protein and its conspicuous repeat units possible functional roles are
      discussed.

PMID- 9232594
TI  - Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective
      tissue and heart.
AB  - The molecular cloning of cDNAs encoding murine fibroblast growth factor-13 (FGF
      13/FHF-2) and three isoforms of murine FGF-12 (FHF-1) is described. Like their
      highly conserved human counterparts, murine FGF-12 and FGF-13 are part of a
      distinct subfamily of FGF-like proteins characterized by a greater degree of
      amino acid sequence cross-homology and by conserved N-terminal domains which do
      not include secretion signal sequences. In addition to their expression in
      several adult tissues, both of these FGF genes are prominently and regionally
      expressed in midgestation mouse embryos, as revealed by in situ hybridization.
      Fgf12 and fgf13. RNAs were detected in developing central nervous system in cells
      outside the proliferating ependymal layer, and fgf13 RNA was also found
      throughout the peripheral nervous system. Fgf12 is expressed in developing soft
      connective tissue of the limb skeleton and in presumptive connective tissue
      linking vertebrae and ribs. Both FGF genes are also expressed in the myocardium
      of the heart, with fgf12 RNA found only in the atrial chamber and fgf13 RNA
      detected in both atrium and ventricle. On the basis of their novel structure and
      patterns of expression, FGF-12 and FGF-13 are anticipated to perform embryonic
      functions distinct from other known FGF molecules.

PMID- 9232595
TI  - The chicken caudal genes establish an anterior-posterior gradient by partially
      overlapping temporal and spatial patterns of expression.
AB  - The caudal genes in vertebrates as in invertebrates assume a posterior position
      along the anterior-posterior axis and they appear to regulate the expression of
      the Hox genes. The third chicken caudal gene, Cdx-C, was cloned. Extensive
      comparisons of the sequence of this protein to the other known members of this
      homeobox family has lead to the suggestion that vertebrate genomes contain three
      members of the caudal homeobox family. A comparative study of the chicken Cdx-A
      and Cdx-C genes during gastrulation and neurulation revealed the differences
      between the genes. The caudal genes exhibit sequential activation in the newly
      formed neural plate and sequential extinction in axial midline structures during
      the primitive streak regression along the anterior-posterior axis. This pattern
      of expression suggests that the number and identity of caudal genes expressed
      along the anterior-posterior axis changes dynamically.

PMID- 9232596
TI  - Chicken NKx2-8, a novel homeobox gene expressed during early heart and foregut
      development.
AB  - cNkx2-8 represents a novel member of the NK2-family transcription factors. The
      gene contains three highly conserved regions, the TN-, NK2-, and homeodomains
      which are diagnostic for this group of proteins. cNkx2-8 is expressed during
      chick embryogenesis in ventral foregut endoderm, myocardial mesoderm, epithelium
      of the branchial arches and the dorsal mesocardium. While cNkx2-8 expression
      partially overlaps with other NK genes, such as Nkx2-5 and Nkx2-3, its onset and
      aspects of its expression domains are specific. Thus, structural data and the
      expression profile suggest that cNkx2-8 constitutes a new homeobox protein which
      may cooperate with its known relatives in defining an antero-ventral field
      including the developing heart and pharyngeal endoderm.

PMID- 9232597
TI  - Combinatorial signaling by Twisted Gastrulation and Decapentaplegic.
AB  - The Twisted Gastrulation (TSG) protein is one of five secreted proteins required
      to pattern the dorsal part of the early Drosophila embryo. Unlike the
      Decapentaplegic (DPP) protein that is required to pattern the entire dorsal half
      of the embryo, TSG is needed only to specify the fate of the dorsal midline
      cells. Here we have misexpressed the tsg gene with different promoters to address
      its mechanism of action and relationship to DPP. When expressed in a ventral
      stripe of cells, TSG protein can diffuse to the dorsalmost cells and can rescue
      the dorsal midline cells in tsg mutant embryos. Despite elevated levels that
      exceed that exceed those needed for biological activity, there was no change in
      dorsal midline or lateral cell fates under any conditions tested. We conclude
      that TSG does not modulate an activity gradient of DPP. Instead, it functions in
      a permissive rather than instructive role to elaborate cell fates along the
      dorsal midline after peak levels of DPP activity have 'primed' cells to respond
      to TSG. The interaction between TSG and DPP defines a novel type of combinatorial
      synergism.

PMID- 9232598
TI  - Survival of inner ear sensory neurons in trk mutant mice.
AB  - Analysis of trkB-/-; trkC-/- double mutant mice revealed that peripheral and
      central inner ear sensory neurons are affected in these mice. However, a
      substantial amount of cochlear and vestibular neurons survive, possibly due to
      maintenance or upregulation of TrkA expression. To clarify the function of the
      TrkA receptor during development of the cochlear and vestibular ganglion we
      analysed trkA-/- mice and the expression of this receptor in inner ear sensory
      neurons of trkB-/-; trkC-/- animals. TrkA homozygous mutant mice showed normal
      numbers of neurons and no TrkA expression was detected in neurons of trkB-/-;
      trkC-/- double mutant mice. We conclude that TrkA is not essential for inner ear
      development and that in the absence of any of the known catalytic Trk receptors
      peripheral inner ear sensory neurons are prone to undergo cell death or must use
      a different signaling mechanism to survive.

PMID- 9232599
TI  - A paired oocyte adhesion assay reveals the homophilic binding properties of the
      Xenopus maternal cadherins, XB/U- and EP-cadherin.
AB  - The homophilic nature of cadherin-mediated cell-cell adhesion provides an
      organism with the opportunity of altering the adhesive capabilities of its cells
      by selectively modulating the expression of different cadherin types.
      Differential cadherin expression is of major importance in regulating the cell
      rearrangements involved in the processes which shape tissues and organs during
      embryogenesis. The pregastrula embryo of Xenopus laevis expresses two maternally
      supplied cadherins: XB/U-cadherin and EP-cadherin. Since these two proteins are
      almost 92% identical at the amino acid level, it was unclear whether heterophilic
      interactions between them were possible. Different functional roles can only be
      ascribed to the two cadherins if the possibility of heterophilic binding between
      them can be excluded. We describe a simple and straightforward assay which can be
      used to assess interactions between adhesion molecules. A combination of
      antisense oligonucleotide and enzyme treatments eliminates endogenous cadherins
      in Xenopus oocytes and subsequent injection of a specific mRNA yields oocytes
      carrying only one or the other cadherin. After removal of the vitelline
      membranes, two oocytes expressing the appropriate cadherins will adhere to one
      another when they are placed in close contact. By scoring for adhesion in
      homotypic and heterotypic pairings, we demonstrate that XB/U-cadherin and EP
      cadherin do not interact with one another.

PMID- 9232600
TI  - Negative regulation of Raf activity by binding of 14-3-3 to the amino terminus of
      Raf in vivo.
AB  - In the developing eye of Drosophila the protein kinase D-Raf controls the
      specification of the R7 photoreceptor cells. We show that overexpression of wild
      type D-Raf inhibits the formation of R7 cells in a dose-dependent manner.
      Conversely, overexpression of mutant D-Raf proteins in which the conserved S388
      is replaced by A or by D promotes the formation of supernumerary R7 cells,
      indicating increased D-Raf activity in vivo. S388 in D-Raf corresponds to S259 in
      c-Raf; shown to be involved in binding of 14-3-3. We show that analogous
      substitutions of S259 in c-Raf prevent binding of 14-3-3 zeta to the amino
      terminus of c-Raf and cause a Ras-independent constitutively increased c-Raf
      kinase activity. Binding of 14-3-3 zeta to the second binding site at the carboxy
      terminal catalytic domain was unaffected by these mutations. These results
      suggest that the increased kinase activity of mutant D-Raf is caused by the
      selective loss of 14-3-3 binding to its amino terminus. Therefore, binding of 14
      3-3 to the amino terminus of Raf appears to negatively regulate Raf kinase
      activity in vivo.

PMID- 9232601
TI  - L-type calcium channel activation controls the in vivo transduction of the
      neuralizing signal in the amphibian embryos.
AB  - We have analyzed the transduction pathways involved in the triggering of neural
      induction, in amphibian embryos, in vivo. Using a plasmid construction, we have
      targetted the bioluminescent calcium probe aequorin to the plasma membrane of
      ectoderm cells of the amphibian Pleurodeles waltl before gastrulation. We have
      demonstrated that the in vivo triggering of neural induction depends on the
      activation of calcium-dependent pathways and involves L-type calcium channels.
      Furthermore, on excised ectoderm taken at the gastrula stage, we show that
      noggin, a protein currently considered as one of the natural inducers, also
      activates L-type calcium channels. This activation represents the first necessary
      event to determine cells of the dorsal ectoderm toward the neural pathway.

PMID- 9232602
TI  - Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation
      produces abnormalities in the early development and regionalization of the
      diencephalon.
AB  - Pax6 expression in the diencephalon of the mouse embryo is restricted both antero
      posteriorly and dorso-ventrally, with changes in level occurring at prosomere
      boundaries. Small eye (Pax6Sey-1Neu) mice homozygous for Pax6 mutations have
      multiple defects in early forebrain development. In the diencephalon of Pax6Sey
      1Neu/Pax6Sey-1Neu mice there is an apparent enlargement of the zona limitans (the
      boundary region between prosomeres p2 and p3), and a blurring of the p1-p2
      boundary. PAX6 function is also required for the normal development of the
      posterior commissure at the midbrain-p1 boundary. In the posterior diencephalon
      PAX6 appears to regulate its own transcription, and that of Wnt7b. In p2 and p3,
      ventral markers are expressed more dorsally than normal, and this is accompanied
      in p3 by a reduction in the size of the zona incerta. Thus, PAX6 is essential for
      the normal development and regionalization of the diencephalon.

PMID- 9232603
TI  - The inhibitory effect on neurite outgrowth of motoneurons exerted by the ligands
      ELF-1 and RAGS.
AB  - Eph-related receptor tyrosine kinases and ligands are expressed at high levels in
      the developing nervous system, giving rise to the proposal that they are involved
      in neuronal connection. Cek8 was found to be predominantly expressed on a subset
      of motoneurons innervating limb but not body muscles during motoneuron axonal
      growth. Here we show that the ligands RAGS and ELF-1 were expressed in limb buds
      and that they activated Cek8 when presented in membrane-bound or clustered forms
      of Fc chimeric proteins but not in unclustered soluble forms. When chick
      embryonic motoneurons enriched by panning were cultured on clustered forms of
      RAGS-Fc and ELF-1-Fc, the neutrite growth of motoneurons expressing Cek8 was
      inhibited. Our results show a relationship between receptor phosphorylation and
      neurite growth inhibition and suggest that Eph-related kinases and ligands have a
      regulatory effect on the axon growth of motoneurons during development.

PMID- 9232604
TI  - Control of midline glia development in the embryonic Drosophila CNS.
AB  - The midline glial cells are required for correct formation of the axonal pattern
      in the embryonic ventral nerve cord of Drosophila. Initially, six midline cells
      form an equivalence group with the capacity to develop as glial cells. By the end
      of embryonic development three to four cells are singled out as midline glial
      cells. Midline glia development occurs in two steps, both of which depend on the
      activation of the Drosophila EGF-receptor homolog and subsequent ras1/raf
      mediated signal transduction. Nuclear targets of this signalling cascade are the
      ETS domain transcription factors pointedP2 and yan. In the midline glia pointedP2
      in turn activates the transcription of argos, which encodes a diffusible negative
      regulator of EGF-receptor signalling.

PMID- 9232605
TI  - Matrix metalloproteinase inhibitors in the treatment of cancer.
AB  - Matrix metalloproteinases are a family of zinc-containing proteolytic enzymes
      that break down extracellular matrix proteins in normal physiological processes
      such as embryogenesis, tissue growth, and wound healing. The family includes
      collagenases, gelatinases, stromelysins and metalloelastase. Observational and
      experimental data from studies of human malignancy indicate that these
      proteinases are induced by the tumour in order to reconstruct adjacent normal
      tissue to allow neovascularisation, tumour growth and spread. Tumours have been
      shown to overexpress certain matrix metalloproteinases relative to normal tissue
      and recent studies have shown an association between high levels of expression
      and poor prognosis. A large series of synthetic inhibitors have been developed
      using the structure of a principal substrate, collagen. The inhibitors contain a
      chemical group that binds the zinc atom in the active site of the metalloenzyme.
      Inhibition is specific for the known matrix metalloproteinase family and is
      reversible. Studies with these inhibitors and native tissue inhibitors of matrix
      metalloproteinases have shown that they can prevent the growth and spread of
      experimental tumours. In other studies, the inhibitors have been shown to be
      directly anti-angiogenic. Synthetic matrix metalloproteinase inhibitors have now
      reached the stage of clinical testing and preliminary results indicate that the
      compounds may be effective in slowing tumour growth. Trials currently underway
      should reveal whether this approach will become a standard part of anti
      neoplastic therapy in the future.

PMID- 9232607
TI  - Enhanced expression of bcl-2 following antisense oligonucleotide mediated growth
      factor deprivation.
AB  - Although the role of bcl-2 in apoptosis has been described, its involvement in
      prostate cancer (CAP) progression is less well understood, but thought to be
      involved with the transition of CAP from androgen-sensitivity to androgen
      independence, where its expression is augmented following androgen ablation. For
      treating these recurrent androgen-independent tumors, following hormone treatment
      failure, a new tier of therapy based upon growth factor deprivation has been
      suggested, implemented by antisense oligonucleotides (oligos) directed against
      mRNA encoding a critical growth regulatory autocrine loop (comprised of
      transforming growth factor-alpha (TGF-alpha) and its binding site, the epidermal
      growth factor receptor (EGFR). To determine whether oligo-induced growth factor
      deprivation therapy similarly enhanced expression of bcl-2 (as follows androgen
      deprivation) human prostate cancer derived PC-3 cells were treated in vitro with
      oligos directed against TGF-alpha (MR-1) and/or EGFR (MR-2). After 5 days of
      treatment cells were immunochemically stained for human bcl-2. In similar
      experiments, cells were treated for 3 days prior to extraction of proteins,
      Western blot analysis, photography and computer evaluation of protein density by
      SigmaScan software. Immunostained cells treated with oligos directed against mRNA
      encoding TGF-alpha (MR-1) either alone or in combination with that directed
      against EGFR (MR-2) had increased bcl-2 expression (+3 to +5). In addition, the
      intensity of Western blots scanned for bcl-2 expression were 19%, 32% and 30%
      greater in cells treated with oligos directed against TGF-alpha, EGFR or their
      combination, respectively. We conclude that enhanced bcl-2 expression followed
      antisense oligo induced growth factor deprivation. This result is similar to that
      found upon androgen deprivation therapy, and also demonstrates additional
      biologic activity of this new class of molecular therapeutic agents.

PMID- 9232606
TI  - Bone marrow transplantation using unrelated donors for haematological
      malignancies.
AB  - Bone marrow transplantation from unrelated donors is increasingly used to treat
      haematological malignancies. There are almost 4 million volunteer donors now
      available. Therefore, it is possible to find an HLA-A, -B and -DR-identical donor
      for around 70% of the patients. The major obstacles to unrelated bone marrow
      transplantations have been rejection, severe acute graft-versus-host disease
      (GVHD) and prolonged immune recovery leading to frequent infections and a high
      transplant-related mortality. However, with improved tissue typing using DNA
      techniques, immunosuppression using T-cell depletion in vitro or in vivo, the
      frequency of acute GVHD is acceptable and the results approach those obtained
      with HLA-identical siblings. For patients with chronic myeloid leukaemia, the
      worldwide 3-year survival is around 40%. Other indications for bone marrow
      transplantation with unrelated marrow include acute leukaemia and myelodysplastic
      syndromes with high-risk features. Unrelated cord blood cells and unrelated
      peripheral blood progenitor cells will be increasingly used as alternative
      haematopoietic stem cell sources to bone marrow. Improved immunosuppression, more
      accurate tissue typing, growth factors and better management of infections is
      expected to improve outcome using unrelated haematopoietic stem cells for
      transplantation in the near future.

PMID- 9232608
TI  - Acute megakaryoblastic leukaemia in a patient with systemic lupus erythematosus.
AB  - We describe here a 72-year-old female patient with an acute megakaryoblastic
      leukaemia (M7 by FAB Classification) and systemic lupus erythematosus (SLE). The
      patient had not been pretreated with immunosuppressive therapy, which is
      potentially leukaemogenic. The karyotype displayed multiple, structural and
      numerical anomalies, suggesting a possible de novo rather than a secondary nature
      of leukaemia.

PMID- 9232609
TI  - Flow cytometric analysis of tumor DNA profile related to response to treatment
      and survival in small-cell lung cancer.
AB  - Flow cytometric (FCM) analysis of tumor DNA ploidy and S-phase fraction (SPF) has
      been widely used to predict prognosis and treatment response in many malignant
      tumors, but rarely in small-cell lung cancer (SCLC). In the present study, tumor
      DNA ploidy and SPF were measured from paraffin-embedded tumor biopsy samples of
      36 small-cell lung cancer patients treated with combination chemotherapy and
      radiotherapy. Aneuploidy was detected in 69% of the tumors. There was a
      statistically non-significant trend towards more aneuploidy among extensive
      disease (ED) patients as compared to patients with limited disease (LD): 80%
      versus 65%, respectively (p = 0.69). The mean SPF was 21.3% (+/-7.6) in patients
      with LD and 29.0% (+/-5.3) in patients with ED, the difference (7.6%) being
      statistically significant (p = 0.008, 95% CI for the difference 2.2-13.1). No
      significant differences was detected in the survival of aneuploid and diploid
      patients or patients with low (< or = 24.9%) and high (> 24.9%) SPF. Similarly,
      no significant difference was observed between aneuploid and diploid cases in
      relation to response to treatment or response duration. It is concluded that the
      difference detected in the SPF with LD and ED of SCLC may indicate the biological
      aggressiveness of extensive SCLC.

PMID- 9232610
TI  - FBL blood test as a predictive marker of breast cancer in high risk women.
AB  - The potential use of the ferritin bearing lymphocytes (FBL) blood test which
      enumerates oncofetal FBL as a biomarker for early breast cancer was explored.
      Analysis of the FBL positive test results carried out on high risk women who
      underwent biopsy in 1983-84 was found to be a significant predictor for early
      breast cancer (relative risk (RR) = 2.9, 95% confidence interval (CI) 1.4-5.8). A
      group of 635 women from the above study diagnosed in 1983-84 as having no
      evidence of breast cancer was further traced 8 years later with the aid of the
      National Cancer Registry. We identified 35 malignancies, including 19 cases of
      breast cancer. The RR of breast cancer for the FBL positive group was 2.51; 95%
      CI = 1.04-6.07 while for the other malignancies it was 0.93, 95% CI = 0.30-2.84.
      All the breast cancer cases in the FBL positive group were of the infiltrative
      duct carcinoma category and 71% were in early stage. In contrast, in the FBL
      negative group, 60% of the cases were infiltrative ductal carcinoma and most of
      them were at stage III. Positive FBL is associated with early manifestation of
      breast cancer and may be considered as a tool for the screening of breast cancer
      in high risk women.

PMID- 9232611
TI  - Therapeutic effect of cyclosporine A in thrombocytopenia after myeloablative
      chemotherapy in acute myeloid leukaemia.
AB  - Four patients with acute myelogenous leukaemia (AML), who developed isolated
      thrombocytopenia after anti-leukaemic chemotherapy, were treated with
      cyclosporine A and showed significantly enhanced platelet recovery. All four
      patients demonstrated decreased bone marrow megakaryocytes without dysplastic
      features, absence of identifiable peripheral autoimmune platelet destruction or
      cytogenetic evidence of secondary myelodysplasia. The duration of response to
      cyclosporine A ranged from 6 days to 40 months. The mechanism of cyclosporine A
      induced platelet recovery may include inhibition of negative modulators and
      induction of thrombopoietic cytokines mediated by bone marrow regulatory cells.

PMID- 9232612
TI  - Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy
      induced oral mucositis in non-neutropenic cancer patients.
AB  - The aim of this study was to assess prospectively the efficacy of granulocyte
      macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy
      induced oral mucositis in non-neutropenic cancer patients. In a prospective open
      study, 30 cancer patients with chemotherapy-induced, neutropenia-independent oral
      mucositis were treated with GM-CSF (Schering Plough Corp, Kenilworth, NJ)
      prepared as a mouthwash solution (5-10 micrograms ml-1). GM-CSF was administered
      within 24 hours of occurrence of oral mucositis x 4 to 6 times daily. Systemic GM
      CSF was not permissible. Oral mucositis was graded according to the modified
      Radiation Therapy Oncology Group criteria. Six patients were subsequently
      excluded as they experienced neutropenia during GM-CSF therapy. The remaining 24
      patients were all evaluable. Most patients had either Grade 3 or 4 gross (76%) or
      functional (54%) mucositis. The mean +/- SEM gross oral mucositis scores for all
      24 patients combined decreased from 3.08 +/- 0.18 at baseline to 2.04 +/- 0.19 (p
      < 0.0001) after 2 days, 0.92 +/- 0.16 (p < 0.0001) after 5 days, and 0.25 +/-
      0.09 (p < 0.0001) after 10 days of therapy. Likewise, the mean +/- SEM functional
      oral mucositis scores decreased from 2.71 +/- 0.18 at baseline to 1.58 +/- 0.19
      (p < 0.0001) after 2 days, 0.75 +/- 0.16 (p < 0.0001) after 5 days, and 0.17 +/-
      0.08 (p < 0.0001) after 10 days of therapy. The duration of severe oral mucositis
      was also shortened as Grade 0 or 1 (gross mucositis score) was evident in seven
      (29%), 20 (83%), and 24 (100%) patients by the 2nd, 5th, and 10th day of therapy,
      respectively. Similarly, Grade 0 or 1 (functional mucositis score) reported in 13
      (54%), 19 (79%), and 24 (100%) by the 2nd, 5th, and 10th day of therapy
      respectively. It was found that GM-CSF mouthwash as used in this study has a
      significant recuperative efficacy on the severity, morbidity, and duration of
      chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study
      is warranted to ascertain that benefit and determine the optimal dosages and
      schedule.

PMID- 9232613
TI  - Classical multidrug resistance in acute myeloid leukaemia.
AB  - Approximately 15-30% of acute myeloid leukaemia (AML) patients are primarily
      resistant to chemotherapy, and 60-80% of patients who achieve complete remission
      will inevitably relapse and succumb to their disease. The multidrug resistant
      (MDR) phenotype has been suspected as a major mechanism of therapy failure in
      AML; it is one of the best understood mechanisms of resistance to anticancer
      drugs. The classical MDR phenotype is characterized by the reduced ability of
      cells to accumulate drugs as compared to normal cells. The increased drug efflux
      is due to the activity of a 170 kDa glycoprotein, the P-glycoprotein (Pgp), a
      unidirectional drug-efflux pump which is encoded by the MDR1 gene. While studies
      of myeloid leukaemia and myeloma have provided the best evidence for the
      potential association between Pgp expression and clinical outcome, the lack of
      standardized methods for MDR detection and perhaps even more importantly,
      inconsistencies in the interpretation of MDR expression data account for
      divergent results in the literature. The clinicians' strong interest in MDR stems
      from the availability of agents capable of interfering with MDR, at least in
      vitro. If these laboratory results were reproducible in vivo, reversal of MDR
      would offer a rare opportunity to incorporate laboratory experience into the
      clinical management of patients.

PMID- 9232614
TI  - Acute leukaemia during tamoxifen therapy.
AB  - Tamoxifen treatment is a proven therapy for breast cancer that produces a
      survival advantage when used as an adjuvant, and reduces the incidence of
      recurrences and controlateral tumor evolution. Although this therapy has a very
      low toxicity profile, an increase in secondary cancers has been reported.
      Tamoxifen is suggested to be carcinogenic both through direct genotoxic and
      epigenetic mechanisms. It is activated by cytochrome P450 to form reactive
      metabolites that bind covalently to DNA to create adducts. We report two cases
      that developed acute myeloid leukaemia (AML) during tamoxifen therapy for breast
      cancer.

PMID- 9232615
TI  - Differentiation of Oesophagostomum bifurcum from Necator americanus by PCR using
      genetic markers in spacer ribosomal DNA.
AB  - Oesophagostomiasis in humans due to infection with Oesophagostomum bifurcum
      (nodular worm) is of major human health significance in northern Togo and Ghana
      where Necator americanus (human hookworm) also exists at high prevalence.
      However, very little is known about the transmission patterns of O. bifurcum,
      partly due to the difficulty in differentiating O. bifurcum from N. americanus at
      some life-cycle stages using morphological features. To overcome this limitation,
      a molecular approach utilizing genetic markers in the second internal transcribed
      spacer (ITS-2) of ribosomal (r) DNA was developed. The ITS-2 sequence of each
      species was determined, and specific oligonucleotide primers were designed to the
      regions of greatest sequence difference between the species. Utilizing these
      primers, rapid PCR assays were developed for the specific amplification of DNA of
      O. bifurcum or N. americanus, which have the potential to confirm the identity of
      eggs from faeces and larvae from the intestine or environment. The application of
      species-specific PCR has important implications for studying the epidemiology and
      population biology of O. bifurcum.

PMID- 9232616
TI  - Molecular discrimination between Campylobacter jejuni, Campylobacter coli,
      Campylobacter lari and Campylobacter upsaliensis by polymerase chain reaction
      based on a novel putative GTPase gene.
AB  - Polymerase chain reaction (PCR) mediated DNA fingerprinting has resulted in the
      identification of a novel Campylobacter jejuni gene, encoding a GTPase protein.
      The gene, consisting of 383 amino acids contained semi-conserved GTP-binding
      sites (designated G-1 to G-4), that are characteristic for members of the GTPase
      protein superfamily. Remarkably, this gene from C. Jejuni appears to encode a
      member of a novel family of GTP-binding proteins, containing two separate
      putative GTP-binding domains, each comprising a series of semi-conserved GTP
      binding motifs. Spacing between these motifs is highly conserved. Based on this
      novel gene, a general PCR strategy for the identification of C. jejuni, C. coli,
      C. lari and C. upsaliensis was developed. PCR primers were deduced from GTP
      binding motifs G-1 and G-3 of the first GTP-binding domain. These GTP-binding
      sites flank a variable region of precisely 117 bp in the four Campylobacter spp.
      that allowed the development of species-specific probes. This PCR-hybridization
      assay offers a novel tool for rapid molecular detection and specific
      identification of the thermophilic Campylobacter spp.

PMID- 9232617
TI  - Amplifiable hybridization probes containing a molecular switch.
AB  - In order to reduce background signals in Q beta replicase-mediated bioassays, a
      target-dependent probe amplification strategy has been proposed that utilizes
      recombinant RNA hybridization probes that contain an inserted molecular switch. A
      molecular switch is an internal region of the probe that undergoes a
      conformational change when the probe hybridizes to its target. We investigated
      whether non-hybridized probes (which cause background signals) could be
      selectively destroyed by incubating the probe-target hybrids with ribonuclease
      III, which should cleave the non-hybridized probes and leave the hybridized
      probes intact. Two problems with this assay design were observed. First,
      ribonuclease III cleaved probe-target hybrids non-specifically when the target
      was an RNA, thereby destroying all of the bound probes. And second, the expected
      conformational change in the molecular switch did not occur when the probes were
      bound to their targets, apparently because the hairpin stem formed by the
      molecular switch was too long. Although these results demonstrated that the
      original assay design could not work, they provided insights that have led to
      better designs for target-dependent amplification assays. In these assays, the
      probes will be DNA molecules containing short-stemmed molecular switches. Non
      hybridized probes will be selectively destroyed by incubation with a restriction
      endonuclease.

PMID- 9232618
TI  - Differentiation of Campylobacter jejuni and Campylobacter coli by polymerase
      chain reaction.
AB  - A multiplex PCR assay was developed using two primer sets for the identification
      and differentiation of Campylobacter coli and Campylobacter jejuni. Primer Set I
      amplifies a 460-bp fragment present in C. coli and C. jejuni. Set II amplifies a
      160-bp target unique to C. jejuni. When the assay was performed on reference
      strains, amplification of C. coli yielded only the 460-bp fragment. Amplification
      of C. jejuni generated both the 160- and 460-bp fragments. Campylobacter field
      strains (n = 85) isolated from raw poultry were identified by PCR and by
      conventional biochemical methods. Species determination by the two methods agreed
      for 83 of the 85 isolates examined. By PCR, 23 were identified as C. coli and 62
      as C. jejuni. One isolate was unidentifiable by biochemical testing. The PCR
      assay identified this isolated as C. coli. In addition, one strain which was
      identified as C. coli by biochemical testing was determined to be C. jejuni by
      PCR. The PCR assay offers an alternative to traditional biochemical typing
      methods for the identification and differentiation of C. coli and C. jejuni
      isolated from poultry. It is accurate, simple to perform, and can be completed
      within 8 h.

PMID- 9232619
TI  - Identification of parasitic nematodes by PCR-SSCP of ITS-2 rDNA.
AB  - Fourteen species of parasitic nematodes (order Strongylida) were characterized
      using a polymerase chain reaction-linked single strand conformation polymorphism
      technique (PCR-SSCP). The rDNA region spanning the second internal transcribed
      spacer (ITS-2) was amplified from parasite DNA by PCR. The PCR products were then
      denatured and subjected to electrophoresis on a non-denaturing gel matrix. PCR
      SSCP of the single stranded ITS-2 molecules generated characteristic and
      reproducible patterns for each species, and allowed the rapid delineation of all
      of the 14 species in one step. The method also allowed the display of variation
      in patterns within some species between different geographical isolates. These
      findings demonstrate the usefulness of PCR-SSCP of ITS-2 for the rapid
      identification of nematode species and indicate its potential for resolving
      variation in the ITS-2 sequence within a species.

PMID- 9232620
TI  - Multiplex PCR for avian pathogenic mycoplasmas.
AB  - Mycoplasma infections are of great concern in avian medicine, because they cause
      economic losses in commercial poultry production. A multiplex polymerase chain
      reaction (PCR) was optimized to simultaneously detect four pathogenic species of
      avian mycoplasmas. Four sets of oligonucleotide primers specific for Mycoplasma
      gallisepticum (MG), M. synoviae (MS), M. meleagridis (MM) and M. iowae (MI) were
      used in the test. By using agarose gel electrophoreses for detection of the PCR
      amplified DNA products, the sensitivity of detection was between 1 pg for MG, 1
      pg for MS, 100 fg for MM and 100 pg for MI after 35 cycles of PCR. Similar
      sensitivity of these primers was achieved with broth cultures of these four
      organisms.

PMID- 9232621
TI  - Clonal X-inactivation analysis of human tumours using the human androgen receptor
      gene (HUMARA) polymorphism: a non-radioactive and semiquantitative strategy
      applicable to fresh and archival tissue.
AB  - Assessment of clonality of cellular proliferations is important in experimental
      and clinical cancer research. X-chromosome inactivation studies are widely used
      to assess clonality, but most assays require relatively large amounts of high
      molecular weight DNA. Two PCR-based strategies, the phosphoglycerate kinase (PGK)
      and the human androgen receptor (HUMARA) clonality assays allow studies of small
      tissue samples. The HUMARA assay was adapted to non-radioactive analysis taking
      advantage of an automated sequencer providing high resolution of alleles and
      immediate quantitation. This assay was validated by comparison with X
      inactivation patterns obtained by Southern analysis with the probes M27 beta and
      PGK. Fifteen gastrointestinal carcinomas, 25 benign goiter nodules and normal
      peripheral leukocytes of 27 individuals (12 who were under 15 years and 15 over
      80 years) were analysed. Furthermore, DNA extracted from formalin-fixed paraffin
      embedded tissue (FPT) was analysed with the two PCR-based methods and compared
      with X-inactivation patterns determined by Southern analysis of high molecular
      weight (HMW) DNA. This modified HUMARA assay is reliable in most patients; as
      with other clonality assays, constitutive skewing in normal tissue precludes
      clonal analysis in some individuals. Extremely skewed X-inactivation patterns
      were found in normal peripheral leukocytes of 7 out of 15 old females (over 80
      years) and in 1 of 12 of the young females tested (under 15 years). Comparison of
      results obtained with HMW and FPT DNA yielded consistent results for the HUMARA
      assay whereas the PGK PCR assay was much less reliable. The HUMARA assay thus
      permits studies of selected areas of tissue sections without significant stromal
      components, allowing correlation of histological and genotype findings in fresh
      and archival specimens.

PMID- 9232622
TI  - Hereditary hemochromatosis: a HpaI polymorphism within the HLA-H gene.

PMID- 9232623
TI  - Absence of the L37P polymorphism in exon 1 of the CDKN2A gene.

PMID- 9232624
TI  - A splice-site mutation affecting the paired box of PAX3 in a three generation
      family with Waardenburg syndrome type I (WS1).
AB  - Waardenburg syndrome, an autosomal dominant disorder characterized by
      sensorineural hearing loss, pigmentary disturbances and other developmental
      defects, is the most frequent form of congenital deafness in humans. Mutations in
      the PAX3 gene, a transcription factor expressed during embryonic development, is
      associated with WS types I and III. Here we report the identification of a novel
      acceptor splice site mutation (86-2 A-->G) in the paired domain of the human PAX3
      gene causing WS type I in a three generation family.

PMID- 9232625
TI  - Detection and differentiation of Epstein-Barr virus strains by in situ polymerase
      chain reaction.
AB  - An in situ polymerase chain reaction (IS-PCR) technique was used to detect and
      differentiate strains of episomal Epstein-Barr virus (EBV) in infected cells. IS
      PCR was performed on cell monolayers in eight-chamber glass slides using EBV type
      specific primer pairs conserved within the EBV-encoded nuclear antigen (EBNA) 3C
      region. The amplicons in the cells were detected by in situ hybridization using
      EBV type-1 and type-2 specific 5'-biotinylated oligonucleotide probes and avidin
      conjugated alkaline phosphatase as secondary reagent. This method was
      successfully used to identify EBV strains not only in Burkitt's lymphoma cell
      lines but also in B cells obtained from a patient with infectious mononucleosis.
      The technique described on this report is a reliable method to detect latently
      infected EBV-positive cells and can potentially be used to identify and type EBV
      strains present in clinical specimens.

PMID- 9232626
TI  - Relation between free fatty acid and acyl-CoA concentrations in rat brain
      following decapitation.
AB  - To ascertain effects of total ischemia on brain phospholipid metabolism,
      anesthetized rats were decapitated and unesterified fatty acids and long chain
      acyl-CoA concentrations were analyzed in brain after 3 or 15 min. Control brain
      was taken from rats that were microwaved. Fatty acids were quantitated by
      extraction, thin layer chromatography and gas chromatography. Long-chain acyl
      CoAs were quantitated by solubilization, solid phase extraction with an
      oligonucleotide purification cartridge and HPLC. Unesterified fatty acid
      concentrations increased significantly after decapitation, most dramatically for
      arachidonic acid (76 fold at 15 min) followed by docosahexaenoic acid. Of the
      acyl-CoA molecular species only the concentration of arachidonoyl-CoA was
      increased at 3 min and 15 min after decapitation, by 3-4 fold compared with
      microwaved brain. The concentration of docosahexaenoyl-CoA fell whereas
      concentrations of the other acyl-CoAs were unchanged. The increase in
      arachidonoyl-CoA after decapitation indicates that reincorporation of arachidonic
      acid into membrane phospholipids is possible during ischemia, likely at the
      expense of docosahexaenoic acid.

PMID- 9232627
TI  - Role of NMDA receptors in pentobarbital tolerance/dependence.
AB  - Effects of continuous pentobarbital administration on binding characteristics of
      [3H]MK-801 in the rat brain were examined by autoradiography. Animals were
      rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300
      micrograms/10 microliters/hr for 7 days) by osmotic minipumps and dependent by
      abrupt withdrawal from pentobarbital. The levels of [3H]MK-801 binding were
      elevated in rats 24-hr after withdrawal from pentobarbital while there were no
      changes except in septum and anterior ventral nuclei in tolerant rats. For
      assessing the role of NMDA receptor in barbiturate action, an NMDA receptor
      antagonist (MK-801, 2.7 femto g/10 microliters/hr) was co-infused with
      pentobarbital. The pentobarbital-infused group had a shorter duration of
      pentobarbital-induced loss of righting reflex (sleeping time) than that of the
      control group, and MK-801 alone did not affect the righting reflex. However, co
      infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions
      induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal
      rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co
      infusion with MK-801. These results suggest the involvement of NMDA receptor up
      regulation in pentobarbital withdrawal and that the development of dependence can
      be attenuated by the treatment of subtoxic dose of MK-801.

PMID- 9232628
TI  - Effects of interferon and PKC modulators on human glioma protein kinase C, cell
      proliferation, and cell cycle.
AB  - The in-vitro effects of human interferon alpha-2b (HuIFN alpha-2b), protein
      kinase C (PKC) agonist [TPA (12-0-tetra-decanoyl-phorbol-13-acetate)] and PKC
      inhibitor (calphostin C) on human glioma (U-373 MG) PKC activity, cell
      proliferation and cell cycle were compared. HuIFN alpha-2b and TPA increased PKC
      activity, elevated the number of cells in DNA synthesis (S) phase and decreased
      cell proliferation by similar magnitudes. Calphostin C inhibited PKC activity,
      increased the number of cells in S phase and produced strong cytotoxic effects
      (IC50 150 nM). Higher concentrations of calphostin C with or without serum
      induced an additional block in gap2 and mitosis. We conclude that HuIFN alpha
      2b's mode of action may be directly or indirectly affecting PKC. The response
      produced by HuIFN alpha-2b is similar to TPA (potent PKC activation and S phase
      arrest).

PMID- 9232629
TI  - Changes in blood-brain barrier nutrient transport in the offspring of iodine
      deficient rats and their preventability.
AB  - Thyroid hormones affect the structure and function of biological membranes.
      Whether or not they affect the Blood-Brain Barrier nutrient transport, the rate
      limiting membrane transport regulating nutrient supply to brain is to be
      established yet. That the impaired brain development and function seen in iodine
      deficiency could be due to such an effect has been assessed in situ by the brain
      uptake index (BUI) method in Wistar/NIN rat pups born to dams subjected to
      dietary iodine deficiency/rehabilitation for different times. Compared to
      controls (C), there was a significant decrease in the BUI values of 2-Deoxy-D
      Glucose (2-DG) and L-leucine (Leu) in the pups (D1) bom to dams chronically fed
      low iodine test (LIT) diet through their active growth and subsequent pregnancy
      and lactation. Surprisingly transport of L-Tyrosine (Tyr) and sucrose (the
      background marker) was not altered, nor was the BBB transport of all these
      nutrients affected by feeding LIT diet during the mothers' gestation (D2) and
      lactation (D3) only. The hypothyroidism in D1 pups was only moderate and
      preventable by rehabilitation of mothers with control diet from conception (R1)
      or parturition (R2), as were the changes in BBB nutrient transport. The results
      suggest that chronic material dietary iodine deficiency impairs BBB nutrient
      transport in the offspring and this could be prevented by their rehabilitation
      with iodine.

PMID- 9232631
TI  - Identification of parvalbumin alpha in bovine hypothalamus: a partial primary
      structure.
AB  - In the course of the study of structure-functional properties and molecular
      mechanisms of neuropeptides and of low molecular weight proteins of the central
      nervous system we succeeded in isolating from the soluble fraction of bovine
      hypothalamus a protein having M(r) 11897.3, according to mass spectral analysis.
      The purification procedure was mainly based on reversed phase HPLC. As the N
      terminus of the molecule was found to be blocked, we have subjected it to CNBr
      degradation. By Edman microsequence analysis of the peptide fragments and by data
      base searching the isolated substance was identified as parvalbumin alpha (PRVA)
      one of the calcium-binding proteins. However, its primary structure was found not
      to be identical to that of the known PRVAs from other sources. One of the
      features of PRVA is its stability. Being subjected to an exhausting purification
      procedure it retains its complete structure. As neuropeptides and low molecular
      weight proteins are found to be polyfunctional, a central question concerns the
      biological role of PRVAs in terms of "where and when" they express their action.

PMID- 9232630
TI  - BDNF and trkB mRNA expression in neurons of the neonatal mouse barrel field
      cortex: normal development and plasticity after cauterizing facial vibrissae.
AB  - Development of the central somatosensory system is profoundly modulated by the
      sensory periphery. Cauterization of facial whiskers alters the segregation
      pattern of barrels in rodents only during a few days just after birth (critical
      period). Although a molecular basis of the segregation of barrel neurons and the
      critical period for the anatomical plasticity observed in layer IV barrel neuron
      is not clear yet, the accumulating evidence suggests that neurotrophins modulate
      synaptic connections including central nervous system. In this study, we showed
      by in situ hybridization that mouse barrel side neurons express brain-derived
      neurotrophic factor (BDNF) mRNA and both catalytic and non-catalytic forms of
      trkB mRNA. Cautery of row C vibrissae on the right side of the face within 24 h
      after birth (post natal day 0, PND0) reduced the expression of BDNF and trkB mRNA
      from the division region between the contralateral row C barrels at PND7. The
      vibrissae in row A, C, and E were cauterized at PND0 followed by quantitative RT
      PCR for BDNF and trkB mRNA with total RNA isolated from the barrel region at
      PND7. The result showed that BDNF, but not trkB, mRNA was increased several-fold
      in the contralateral barrel region. These data suggest that the expression of
      BDNF mRNA is differentially regulated between injured barrels and actively
      innervated barrels. The differential expression of the mRNA encoding
      neurotrophins and their receptors may be important in regulating the injury
      dependent re-segregation of barrels.

PMID- 9232632
TI  - Metal cations defibrillize the amyloid beta-protein fibrils.
AB  - Amyloid beta-protein (A beta) is the major constituent of amyloid fibrils
      composing beta-amyloid plaques and cerebrovascular amyloid in Alzheimer's disease
      (AD). We studied the effect of metal cations on preformed fibrils of synthetic A
      beta by Thioflavin T (ThT) fluorescence spectroscopy and electronmicroscopy (EM)
      in negative staining. The amount of cross beta-pleated sheet structure of A beta
      1-40 fibrils was found to decrease by metal cations in a concentration-dependent
      manner as measured by ThT fluorescence spectroscopy. The order of
      defibrillization of A beta 1-40 fibrils by metal cations was: Ca2+ and Zn2+ (IC50
      = 100 microM) > Mg3+ (IC50 = 300 microM) > Al3+ (IC50 = 1.1 mM). EM analysis in
      negative staining showed that A beta 1-40 fibrils in the absence of cations were
      organized in a fine network with a little or no amorphous material. The addition
      of Ca2+, Mg2+, and Zn2+ to preformed A beta 1-40 fibrils defibrillized the
      fibrils or converted them into short rods or to amorphous material. Al3+ was less
      effective, and reduced the fibril network by about 80% of that in the absence of
      any metal cation. Studies with A beta 1-42 showed that this peptide forms more
      dense network of fibrils as compared to A beta 1-40. Both ThT fluorescence
      spectroscopy and EM showed that similar to A beta 1-40, A beta 1-42 fibrils are
      also defibrillized in the presence of millimolar concentrations of Ca2+. These
      studies suggest that metal cations can defibrillize the fibrils of synthetic A
      beta.

PMID- 9232633
TI  - Myelin basic protein is a zinc-binding protein in brain: possible role in myelin
      compaction.
AB  - The zinc-binding proteins (ZnBPs) in porcine brain were characterized by the
      radioactive zinc-blot technique. Three ZnBPs of molecular weights about 53 kDa,
      42 kDa, and 21 kDa were identified. The 53 kDa and 42 kDa ZnBPs were found in all
      subcellular fractions while the 21 kDa ZnBP was mainly associated with
      particulate fractions. This 21 kDa ZnBP was identified by internal protein
      sequence data as the myelin basic protein. Further characterization of its
      electrophoretic properties and cyanogen bromide cleavage pattern with the
      authentic protein confirmed its identity. The zinc binding properties of myelin
      basic protein are metal specific, concentration dependent and pH dependent. The
      zinc binding property is conferred by the histidine residues since modification
      of these residues by diethyl-pyrocarbonate would abolish this activity.
      Furthermore, zinc ion was found to potentiate myelin basic protein-induced
      phospholipid vesicle aggregation. It is likely that zinc plays an important role
      in myelin compaction by interacting with myelin basic protein.

PMID- 9232634
TI  - Detection of cystathionine ketimine and lanthionine ketimine in human brain.
AB  - The sulfur containing imino acids cystathionine ketimine (CK) and lanthionine
      ketimine (LK) have been detected in the human brain by an HPLC procedure. The
      HPLC procedure takes advantage of the selective absorbance at 380 nm of the
      phenylisothiocyanate-ketimine adduct. Quantitation of cystathionine ketimine and
      lanthionine ketimine indicates a mean concentration (mean +/- SD, n = 4) of 2.3
      +/- 0.8 nmol/g for CK and of 1.1 +/- 0.3 nmol/g for LK in four human cerebral
      cortex samples of neurosurgical source. The identification of these cyclic
      ketimine derivatives of L-cystathionine and L-lanthionine as normal human
      metabolites in human nervous tissue may have interesting metabolic and
      physiological implications.

PMID- 9232635
TI  - L-alpha-aminoadipate inhibits kynurenate synthesis in rat brain hippocampus and
      tissue culture.
AB  - Intracerebral administration of L-alpha-aminoadipic acid (L-AAA) at 500 mg/kg
      body weight to rats caused a complex behavioral change with sporadic wet-dog
      shakes. Animals developed severe limbic seizures between 1 and 6 h after L-AAA
      injection, characterized by generalized convulsions. Twenty days after L-AAA
      injection kynurenine aminotransferase (KAT) activity measured in hippocampal
      brain tissue slices prepared with a McIlwain chopper at 30 microns showed a
      significant 43% decrease. Subcutaneous injection of kynurenine at 500 mg/kg
      showed a 63% increase in KAT activity twenty days later. This increase was offset
      by a concomitant administration of 500 mg/kg L-AAA stereotaxically on day one. In
      astrocyte culture kynurenic acid synthesis is inhibited by L-AAA and L-pipecolic
      acid. The possible involvement of kynurenic acid in the modulation of neuronal
      degeneration is discussed.

PMID- 9232636
TI  - Secretory vesicle pools and rate and kinetics of single vesicle exocytosis in
      neurosecretory cells.
AB  - Secretory vesicles are localized in specific compartments within neurosecretory
      cells. Morphometric, cytochemical and electrophysiological techniques have
      allowed the definition of secretory vesicle compartments. These are different
      pools in which vesicles are in various states of releasability. The transit of
      vesicles between compartments is not random, but an event controlled and
      regulated by Ca2+ and the cortical F-actin network. Cortical F-actin disassembly,
      a Ca(2+)-dependent event, controls the transit of secretory vesicles from the
      reserve compartment to the release-ready vesicle pool. Furthermore, the recent
      development of new technical approaches (patch-clamp membrane capacitance,
      electrochemical detection of amines with carbon-fibre microelectrodes) has now
      permitted us to understand the kinetics of single vesicle exocytosis.

PMID- 9232637
TI  - [Disinfection and sterilization of endoscopes in urology. The Committee on
      Infection of the French Association of Urology].

PMID- 9232638
TI  - Conformational substates in enzyme mechanism: the 120 K structure of alpha-lytic
      protease at 1.5 A resolution.
AB  - Insight into the dynamic properties of alpha-lytic protease (alpha LP) has been
      obtained through the use of low-temperature X-ray crystallography and multiple
      conformation refinement. Previous studies of alpha LP have shown that the
      residues around the active site are able to move significantly to accommodate
      substrates of different sizes. Here we show a link between the ability to
      accommodate ligands and the dynamics of the binding pocket. Although the
      structure of alpha LP at 120 K has B-factors with a uniformly low value of 4.8 A2
      for the main chain, four regions stand out as having significantly higher B
      factors. Because thermal motion should be suppressed at cryogenic temperatures,
      the high B-factors are interpreted as the result of trapped conformational
      substates. The active site residues that are perturbed during accommodation of
      different substrates are precisely those showing conformational substates,
      implying that substrate binding selects a subset of conformations from the
      ensemble of accessible states. To better characterize the precise nature of these
      substates, a protein model consisting of 16 structures has been refined and
      evaluated. The model reveals a number of features that could not be well
      described by conventional B-factors: for example, 40% of the main-chain residue
      conformations are distributed asymmetrically or in discrete clusters.
      Furthermore, these data demonstrate an unexpected correlation between motions on
      either side of the binding pocket that we suggest is a consequence of "dynamic
      close packing." These results provide strong evidence for the role of protein
      dynamics in substrate binding and are consistent with the results of dynamic
      studies of ligand binding in myoglobin and ribonuclease A.

PMID- 9232639
TI  - Conformational stability of ribonuclease T1 determined by hydrogen-deuterium
      exchange.
AB  - The hydrogen-deuterium exchange kinetics of 37 backbone amide residues in RNase
      T1 have been monitored at 25, 40, 45, and 50 degrees C at pD 5.6 and at 40 and 45
      degrees C at pD 6.6. The hydrogen exchange rate constants of the hydrogen-bonded
      residues varied over eight orders of magnitude at 25 degrees C with 13 residues
      showing exchange rates consistent with exchange occurring as a result of global
      unfolding. These residues are located in strands 2-4 of the central beta-pleated
      sheet. The residues located in the alpha-helix and the remaining strands of the
      beta-sheet exhibited exchange behaviors consistent with exchange occurring due to
      local structural fluctuations. For several residues at 25 degrees C, the global
      free energy change calculated from the hydrogen exchange data was over 2 kcal/mol
      greater than the free energy of unfolding determined from urea denaturation
      experiments. The number of residues showing this unexpected behavior was found to
      increase with temperature. This apparent inconsistency can be explained
      quantitatively if the cis-trans isomerization of the two cis prolines, Pro-39 and
      Pro-55, is taken into account. The cis-trans isomerization equilibrium calculated
      from kinetic data indicates the free energy of the unfolded state will be 2.6
      kcal/mol higher at 25 degrees C when the two prolines are cis rather than trans
      (Mayr LM, Odefey CO, Schutkowski M, Schmid FX. 1996. Kinetic analysis of the
      unfolding and refolding of ribonuclease T1 by a stopped-flow double-mixing
      technique. Biochemistry 35: 5550-5561). The hydrogen exchange results are
      consistent with the most slowly exchanging hydrogens exchanging from a globally
      higher free energy unfolded state in which Pro-55 and Pro-39 are still
      predominantly in the cis conformation. When the conformational stabilities
      determined by hydrogen exchange are corrected for the proline isomerization
      equilibrium, the results are in excellent agreement with those from an analysis
      of urea denaturation curves.

PMID- 9232640
TI  - Design and characterization of the anion-sensitive coiled-coil peptide.
AB  - As a model for analyzing the role of charge repulsion in proteins and its
      shielding by the solvent, we designed a peptide of 27 amino acid residues that
      formed a homodimeric coiled-coil. The interface between the coils consisted of
      hydrophobic Leu and Val residues, and 10 Lys residues per monomer were
      incorporated into the positions exposed to solvent. During the preparation of a
      disulfide-linked dimer in which the two peptides were linked in parallel by the
      two disulfide bonds located at the N and C terminals, a cyclic monomer with an
      intramolecular disulfide bond was also obtained. On the basis of CD and 1H-NMR,
      the conformational stabilities of these isomers and several reference peptides
      were examined. Whereas all these peptides were unfolded in the absence of salt at
      pH 4.7 and 20 degrees C, the addition of NaClO4 cooperatively stabilized the
      alpha-helical conformation. The crosslinking of the peptides by disulfide bonds
      significantly decreased the midpoint salt concentration of the transition. The 1H
      NMR spectra in the presence of NaClO4 suggested that, whereas the disulfide
      bonded dimer assumed a native-like conformation, the cyclic monomer assumed a
      molten globule-like conformation with disordered side chains. However, the cyclic
      monomer exhibited cooperative transitions against temperature and Gdn-HCl that
      were only slightly less cooperative than those of the disulfide-bonded parallel
      dimer. These results indicate that the charge repulsion critically destabilizes
      the native-like state as well as the molten globule-like state, and that the
      solvent-dependent charge repulsion may be useful for controlling the conformation
      of designed peptides.

PMID- 9232642
TI  - The crystal structure of human alpha-thrombin complexed with LY178550, a
      nonpeptidyl, active site-directed inhibitor.
AB  - The crystal structure of human alpha-thrombin in complex with LY178550, a
      nonpeptidyl, active site-directed inhibitor, has been solved to 2.07 A resolution
      by the method of X-ray crystallography. The final model of the complex has a
      crystallographic R-value of 21.5% (Rfree = 23.1%) with 0.014 A and 2.4 degrees
      standard deviation from ideal bond lengths and angles, respectively. Well-defined
      electron density was observed for the inhibitor in the active site. The inhibitor
      binds to the active site in an L-shaped manner, mimicking the bound conformation
      of the tripeptide arginal series of thrombin inhibitors (Chirgadze NY et al.,
      1992, American Crystallographic Association Meeting 20: 116 [Abstr. PB311]). The
      basic amidine of LY178550 forms a salt bridge with Asp 189 within the specificity
      pocket, while the 4-benzylpiperidine side chain engages in a number of
      hydrophobic interactions at the S2 and S3 binding sites. The inhibitor does not
      interact in any fashion with the active site sequence Ser 214-Gly 216, as occurs
      with many of the inhibitors studied previously. The indole N-H of the inhibitor
      forms a hydrogen bond to the gamma-oxygen of the catalytic serine (Ser 195).

PMID- 9232641
TI  - Synthesis and characterization of histidine-phosphorylated peptides.
AB  - Posttranslational phosphorylation of proteins is an important event in many
      cellular processes. Whereas phosphoesters of serine, threonine, and tyrosine have
      been studied extensively, only limited information is available for other amino
      acids modified by a phosphate group. The formation of phosphohistidine residues
      in proteins was discovered originally in prokaryotic organisms, but also has been
      found recently in eukaryotic cells. We describe methods for the synthesis and
      analysis of phosphohistidine-containing peptides, a prerequisite for the
      investigation of the role of this posttranslational modification in cellular
      processes.

PMID- 9232643
TI  - The crystal structure of the mouse glandular kallikrein-13 (prorenin converting
      enzyme).
AB  - A crystal structure of the serine protease, mouse glandular kallikrein 13 (mGK
      13) has been determined at 2.6-A resolution. This enzyme, isolated from the mouse
      submandibular gland, is also known as prorenin-converting enzyme and cleaves
      submandibular gland Ren-2 prorenin to yield active renin. The mGK-13 structure is
      similar to other members of the mammalian serine protease family, having five
      conserved disulfide bonds and an active site located in the cleft between two
      beta-barrel domains. The mGK-13 structure reveals for the first time an ordered
      kallikrein loop conformation containing a short 3(10) helix. This loop is
      disordered in the related porcine pancreatic kallikrein and rat submandibular
      tonin structures. The kallikrein loop is in close spatial proximity to the active
      site and is also involved in a dimeric arrangement of mGK-13. The catalytic
      specificity of mGK-13 for Ren-2 prorenin was studied by modeling a prorenin
      derived peptide into the active site of mGK-13. This model emphasizes two
      electronegative substrate specificity pockets on the mGK-13 surface, which could
      accommodate the dibasic P2 and P1 residues at the site of prorenin cleavage by
      mGK-13.

PMID- 9232644
TI  - Hydrophobic folding units at protein-protein interfaces: implications to protein
      folding and to protein-protein association.
AB  - A hydrophobic folding unit cutting algorithm, originally developed for dissecting
      single-chain proteins, has been applied to a dataset of dissimilar two-chain
      protein-protein interfaces. Rather than consider each individual chain
      separately, the two-chain complex has been treated as a single chain. The two
      chain parsing results presented in this work show hydrophobicity to be a critical
      attribute of two-state versus three-state protein-protein complexes. The
      hydrophobic folding units at the interfaces of two-state complexes suggest that
      the cooperative nature of the two-chain protein folding is the outcome of the
      hydrophobic effect, similar to its being the driving force in a single-chain
      folding. In analogy to the protein-folding process, the two-chain, two-state
      model complex may correspond to the formation of compact, hydrophobic nuclei. On
      the other hand, the three-state model complex involves binding of already folded
      monomers, similar to the association of the hydrophobic folding units within a
      single chain. The similarity between folding entities in protein cores and in two
      state protein-protein interfaces, despite the absence of some chain
      connectivities in the latter, indicates that chain linkage does not necessarily
      affect the native conformation. This further substantiates the notion that
      tertiary, non-local interactions play a critical role in protein folding. These
      compact, hydrophobic, two-chain folding units, derived from structurally
      dissimilar protein-protein interfaces, provide a rich set of data useful in
      investigations of the role played by chain connectivity and by tertiary
      interactions in studies of binding and of folding. Since they are composed of non
      contiguous pieces of protein backbones, they may also aid in defining folding
      nuclei.

PMID- 9232645
TI  - The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2:
      movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand
      binding.
AB  - Unliganded bovine alpha-thrombin and prethrombin-2 have been co-crystallized, in
      space group P21212, using either ammonium sulfate or polyethylene glycol 2000
      (PEG2K), and their structures determined at 2.2 A and 2.3 A, respectively.
      Initial phases were determined by molecular replacement and refined using XPLOR
      to final R factors of 0.187 (Rfree = 0.255) and 0.190 (Rfree = 0.282) for the
      salt and PEG2K models, respectively. The apo-enzyme form of bovine alpha-thrombin
      shows dramatic shifts in placement for the Tyr-Pro-Pro-Trp segment, for Glu-192,
      and for the catalytic residues His-57 and Ser-195, when compared to 4 thrombin
      complexes representing different states of catalysis, namely (1) the Michaelis
      complex (residues 7-19 of fibrinogen A alpha with a non-cleavable scissile bond),
      (2) enzyme-inhibitor complex (D-Phe-Pro-Arg chloromethylketone), (3) enzyme
      product complex (residues 7-16 of fibrinopeptide A), and (4) the exosite complex
      (residues 53-64 of hirudin). The structures of bovine and human prethrombin-2 are
      generally similar to one another (RMS deviation of 0.68 A) but differ
      significantly in the Arg-15/Ile-16 cleavage region and in the three activation
      domains, which are disordered in bovine prethrombin-2, analogous to that seen for
      trypsinogen.

PMID- 9232646
TI  - Absence of a stable intermediate on the folding pathway of protein A.
AB  - The B-domain of protein A has one of the simplest protein topologies, a three
      helix bundle. Its folding has been studied as a model for elementary steps in the
      folding of larger proteins. Earlier studies suggested that folding might occur by
      way of a helical hairpin intermediate. Equilibrium hydrogen exchange measurements
      indicate that the C-terminal helical hairpin could be a potential folding
      intermediate. Kinetic refolding experiments were performed using stopped-flow
      circular dichroism and NMR hydrogen-deuterium exchange pulse labeling. Folding of
      the entire molecule is essentially complete within the 6 ms dead time of the
      quench-flow apparatus, indicating that the intermediate, if formed, progresses
      rapidly to the final folded state. Site-directed mutagenesis of the isoleucine
      residue at position 16 was used to generate a variant protein containing
      tryptophan (the 116 W mutant). The formation of the putative folding intermediate
      was expected to be favored in this mutant at the expense of the native folded
      form, due to predicted unfavorable steric interactions of the bulky tryptophan
      side chain in the folded state. The 116 W mutant refolds completely within the
      dead time of a stopped-flow fluorescence experiment. No partly folded
      intermediate could be detected by either kinetic or equilibrium measurements.
      Studies of peptide fragments suggest that the protein A sequence has an intrinsic
      propensity to form a helix II/helix III hairpin. However, its stability appears
      to be marginal (of the order of 1/2 kT) and it could not be an obligatory
      intermediate on a defined folding pathway. These results explicitly demonstrate
      that the protein A B domain folds extremely rapidly by an apparent two-state
      mechanism without formation of stable partly folded intermediates. Similar
      mechanisms may also be involved in the rapid folding of subdomains of larger
      proteins to form the compact molten globule intermediates that often accumulate
      during the folding process.

PMID- 9232647
TI  - Structure-based subsite specificity mapping of human cathepsin D using statine
      based inhibitors.
AB  - Human cathepsin D is a lysosomal aspartic protease that has been implicated in
      breast cancer metastasis and Alzheimer's disease. Based on a crystal structure of
      a human cathepsin D-pepstatin A complex, a series of statine-containing
      inhibitors was designed, synthesized, and tested for inhibitory activity toward
      the enzyme in vitro. The compounds were modified systematically at individual
      positions (P4, P3, P2, P1, and P2t) with the aim of mapping the cathepsin D
      subsite preferences. The experimentally obtained SAR data were correlated on the
      basis of molecular modeling. Side-chain preferences for the peptidomimetic
      inhibitors differed from those found previously using peptide substrates
      (Scarborough PE et al., 1993, Protein Sci 2:264-276). In addition, the effects of
      single side-chain modifications were often nonadditive. Structure-activity
      relationships, modeling, and thermodynamic analysis indicated that entropy plays
      a major stabilizing role in inhibitor binding to cathepsin D.

PMID- 9232648
TI  - Statistical significance of hierarchical multi-body potentials based on Delaunay
      tessellation and their application in sequence-structure alignment.
AB  - Statistical potentials based on pairwise interactions between C alpha atoms are
      commonly used in protein threading/fold-recognition attempts. Inclusion of higher
      order interaction is a possible means of improving the specificity of these
      potentials. Delaunay tessellation of the C alpha-atom representation of protein
      structure has been suggested as a means of defining multi-body interactions. A
      large number of parameters are required to define all four-body interactions of
      20 amino acid types (20(4) = 160,000). Assuming that residue order within a four
      body contact is irrelevant reduces this to a manageable 8,855 parameters, using a
      nonredundant dataset of 608 protein structures. Three lines of evidence support
      the significance and utility of the four-body potential for sequence-structure
      matching. First, compared to the four-body model, all lower-order interaction
      models (three-body, two-body, one-body) are found statistically inadequate to
      explain the frequency distribution of residue contacts. Second, coherent patterns
      of interaction are seen in a graphic presentation of the four-body potential.
      Many patterns have plausible biophysical explanations and are consistent across
      sets of residues sharing certain properties (e.g., size, hydrophobicity, or
      charge). Third, the utility of the multi-body potential is tested on a test set
      of 12 same-length pairs of proteins of known structure for two protocols:
      Sequence-recognizes-structure, where a query sequence is threaded (without gap)
      through the native and a non-native structure; and structure-recognizes-sequence,
      where a query structure is threaded by its native and another non-native
      sequence. Using cross-validated training, protein sequences correctly recognized
      their native structure in all 24 cases. Conversely, structures recognized the
      native sequence in 23 of 24 cases. Further, the score differences between correct
      and decoy structures increased significantly using the three- or four-body
      potential compared to potentials of lower order.

PMID- 9232649
TI  - Effect of limited proteolysis on the stability and enzymatic activity of human
      placental S-adenosylhomocysteine hydrolase.
AB  - Human placental S-adenosylhomocysteine (AdoHcy) hydrolase was subjected to
      limited papain digestion. The multiple cleavage sites in the enzyme were
      identified to be Lys94-Ala95, Tyr100-Ala101, Glu243-Ile244, Met367-Ala368, Gln369
      Ile370, and Gly382-Val383. Despite multiple cleavage sites in the backbone of the
      protein, the digested enzyme was able to maintain its quaternary structure and
      retain its full catalytic activity. The enzyme activity of the partially digested
      AdoHcy hydrolase was essentially identical to that of the native enzyme at
      several pH values. The thermal stabilities of the native and partially digested
      enzymes were only slightly different at all temperatures tested. The stability of
      both native and partially digested enzymes were examined in guanidine
      hydrochloride and equilibrium unfolding transitions were monitored by CD
      spectroscopy and tryptophan fluorescence spectroscopy. The results of these
      experiments can be summarized as follows: (1) CD spectroscopic analysis showed
      that the overall secondary and tertiary structures of the partially digested
      enzyme are essentially identical with those of the native enzyme; and (2)
      tryptophan fluorescence spectroscopic analysis indicated that there are small
      differences in the environments of surface-exposed tryptophan residues between
      the partially digested enzyme and the native enzyme under unfolding conditions.
      The differences in the free energy of unfolding, delta(delta Gu) [delta
      Gu(native)-delta Gu(digested)], is approximately 1.3 kcal/mol. When NAD+ was
      removed from the partially digested enzyme, the secondary and tertiary structures
      of the apo form of the digested AdoHcy hydrolase were completely lost and the
      enzymatic activity could not be recovered by incubation with excess NAD+. These
      results suggest that AdoHcy hydrolase exists as a very compact enzyme with
      extensive intramolecular bonding, which contributes significantly to the overall
      global protein stabilization. Identification of the surface-exposed peptide
      bonds, which are susceptible to papain digestion, has provided some constraints
      on the spatial orientations of subunits of the enzyme. This information, in turn,
      has provided supplemental data for X-ray crystallographic studies currently
      ongoing in our laboratories.

PMID- 9232650
TI  - Temperature control for kinetic refolding of heat-denatured ovalbumin.
AB  - The folding of heat-denatured ovalbumin, a non-inhibitory serpin with a molecular
      size of 45 kDa, was examined. Ovalbumin was heat-denatured at 80 degrees C under
      nonreducing conditions at pH 7.5 and then cooled either slowly or rapidly. Slow
      cooling allowed the heat-denatured ovalbumin to refold to its native structure
      with subsequent resistance to digestion by trypsin. Upon rapid cooling, by
      contrast, the heat-denatured molecules assumed the metastable non-native
      conformations that were susceptible to trypsin. The non-native species were
      marginally stable for several days at a low temperature, but the molecules were
      transformed slowly into the native conformation. Considering data from size
      exclusion chromatography and from analyses of CD, intrinsic tryptophan
      fluorescence, and adsorption of the dye 1-anilinonaphthalene-8-sulfonate, we
      postulated that the non-native species that accumulated upon rapid cooling were
      compact but structureless globules with disordered side chains collectively as a
      folding intermediate. Temperature-jumped CD experiments revealed biphasic
      kinetics for the refolding process of heat-denatured ovalbumin, with the features
      of increasing and subsequently decreasing amplitude of the rapid and the slow
      phases, respectively, with the decrease in folding temperature. The temperature
      dependence of the refolding kinetics indicated that the yield of renaturation was
      maximal at about 55 degrees C. These findings suggested the kinetic partitioning
      of heat-denatured ovalbumin between alternative fates, slow renaturation to the
      native state and rapid collapse to the metastable intermediate state. Analysis of
      disulfide pairing revealed the formation of a scrambled form with non-native
      disulfide interactions in both the heat-denatured state and the intermediate
      state that accumulated upon rapid cooling, suggesting that non-native disulfide
      pairing is responsible for the kinetic barriers that retard the correct folding
      of ovalbumin.

PMID- 9232651
TI  - Binding of monoclonal antibody 4B1 to homologs of the lactose permease of
      Escherichia coli.
AB  - The conformationally sensitive epitope for monoclonal antibody (mAb) 4B1, which
      uncouples lactose from H+ translocation in the lactose permease of Escherichia
      coli, is localized in the periplasmic loop between helices VII and VIII (loop
      VII/VIII) on one face of a short helical segment (Sun J, et al., 1996,
      Biochemistry 35;990-998). Comparison of sequences in the region corresponding to
      loop VII/VIII in members of Cluster 5 of the Major Facilitator Superfamily (MFS),
      which includes five homologous oligosaccharide/H+ symporters, reveals interesting
      variations. 4B1 binds to the Citrobacter freundii lactose permease or E. coli
      raffinose permease with resultant inhibition of transport activity. Because E.
      coli raffinose permease contains a Pro residue at position 254 rather than Gly,
      it is unlikely that the mAb recognizes the peptide backbone at this position.
      Consistently, E. coli lactose permease with Pro in place of Gly254 also binds
      4B1. In contrast, 4B1 binding is not observed with either Klebsiella pneumoniae
      lactose permease or E. coli sucrose permease. When the epitope is transferred
      from E. coli lactose permease (residues 245-259) to the sucrose permease, the
      modified protein binds 4B1, but the mAb has no significant effect on sucrose
      transport. The studies provide further evidence that the 4B1 epitope is
      restricted to loop VII/VIII, and that 4B1 binding induces a highly specific
      conformational change that uncouples substrate and H+ translocation.

PMID- 9232652
TI  - Tetranectin, a trimeric plasminogen-binding C-type lectin.
AB  - Tetranectin, a plasminogen-binding protein belonging to the family of C-type
      lectins, was expressed in E. coli and converted to its native form by in vitro
      refolding and proteolytic processing. Recombinant tetranectin-as well as natural
      tetranectin from human plasma-was shown by chemical cross-linking analysis and
      SDS-PAGE to be a homo-trimer in solution as are other known members of the
      collectin family of C-type lectins. Biochemical evidence is presented showing
      that an N-terminal domain encoded within exons 1 and 2 of the tetranectin gene is
      necessary and sufficient to govern subunit trimerization.

PMID- 9232653
TI  - Structural studies of receptor binding by cholera toxin mutants.
AB  - The wide range of receptor binding affinities reported to result from mutations
      at residue Gly 33 of the cholera toxin B-pentamer (CTB) has been most puzzling.
      For instance, introduction of an aspartate at this position abolishes receptor
      binding, whereas substitution by arginine retains receptor affinity despite the
      larger side chain. We now report the structure determination and 2.3-A refinement
      of the CTB mutant Gly 33-->Arg complexed with the GM1 oligosaccharide, as well as
      the 2.2-A refinement of a Gly 33-->Asp mutant of the closely related Escherichia
      coli heat-labile enterotoxin B-pentamer (LTB). Two of the five receptor binding
      sites in the Gly 33-->Arg CTB mutant are occupied by bound GM1 oligosaccharide;
      two other sites are involved in a reciprocal toxin:toxin interaction; one site is
      unoccupied. We further report a higher resolution (2.0 A) determination and
      refinement of the wild-type CTB:GM1 oligosaccharide complex in which all five
      oligosaccharides are seen to be bound in essentially identical conformations.
      Saccharide conformation and binding interactions are very similar in both the CTB
      wild-type and Gly 33-->Arg mutant complexes. The protein conformation observed
      for the binding-deficient Gly 33-->Asp mutant of LTB does not differ
      substantially from that seen in the toxin:saccharide complexes. The critical
      nature of the side chain of residue 33 is apparently due to a limited range of
      subtle rearrangements available to both the toxin and the saccharide to
      accommodate receptor binding. The intermolecular interactions seen in the CTB
      (Gly 33-->Arg) complex with oligosaccharide suggest that the affinity of this
      mutant for the receptor is close to the self-affinity corresponding to the
      toxin:toxin binding interaction that has now been observed in crystal structures
      of three CTB mutants.

PMID- 9232654
TI  - Mutational analysis of hydrophobic domain interactions in gamma B-crystallin from
      bovine eye lens.
AB  - gamma B-crystallin is a monomeric member of the beta gamma-superfamily of
      vertebrate eye lens proteins. It consists of two similar domains with all-beta
      Greek key topology associating about an approximate two-fold axis. At pH 2, with
      urea as the denaturant, the domains show independent equilibrium unfolding
      transitions, suggesting different intrinsic stabilities. Denaturation experiments
      using recombinant one- or two-domain proteins showed that the N-terminal domain
      on its own exhibits unaltered intrinsic stability but contributes significantly
      to the stability of its C-terminal partner. It has been suggested that docking of
      the domains is determined by a hydrophobic interface that includes phenylalanine
      at position 56 of the N-terminal domain. In order to test this hypothesis, F56
      was substituted by site-directed mutagenesis in both complete gamma B-crystallin
      and its isolated N-terminal domain. All mutations destabilize the N-terminal
      domain to about the same extent but affect the C-terminal domain in a different
      way. Replacement by the small alanine side chain or the charged aspartic acid
      residue results in a significant destabilization of the C-terminal domain,
      whereas the more bulky tryptophan residue causes only a moderate decrease in
      stability. In the mutants F56A and F56D, equilibrium unfolding transitions
      obtained by circular dichroism and intrinsic fluorescence differ, suggesting a
      more complex denaturation behavior than the one observed for gamma B wild type.
      These results confirm how mutations in one crystallin domain can affect the
      stability of another when they occur at the interface. The results strongly
      suggest that size, hydrophobicity, and optimal packing of amino acids involved in
      these interactions are critical for the stability of gamma B-crystallin.

PMID- 9232655
TI  - Epitope and mimotope for an antibody to the Na, K-ATPase.
AB  - The epitope of a monoclonal antibody specific for the alpha 2 isoform of the Na,K
      ATPase was determined and its accessibility in native enzyme was examined.
      Protein fragmentation with N-chlorosuccinimide, formic acid, trypsin, and leucine
      aminopeptidase indicated binding near the Na,K-ATPase N-terminus but did not
      unambiguously delineate the extent of the epitope. The ability of the antibody to
      bind to denatured enzyme made it a good candidate for screening a random peptide
      library displayed on M13 phage, but the consensus sequence that emerged was not
      found in the Na,K-ATPase, Full-length cDNA for the Na,K-ATPase was randomly
      fragmented and cloned into beta-galactosidase to create a lambda gt11 expression
      library; screening with the antibody yielded a set of overlaps spanning 23 amino
      acids at the N-terminus. Chimeras of Na,K-ATPase alpha 1 and alpha 2 narrowed
      down the epitope to 14-19 amino acids. The antibody did not recognize fusion
      proteins constructed with shorter segments of this epitope. It did recognize a
      fusion protein containing the M13 library consensus sequence, however, indicating
      that this sequence, which is rich in proline and hydrophobic amino acids
      (FPPNFLFPPPP), was a mimotope. The natural epitope, unique to the Na,K-ATPase
      alpha 2 isoform, was GREYSPAATTAENG. Reconstitution of antibody binding in a
      foreign context such as M13 PIII protein or beta-galactosidase thus required a
      relatively large number of amino acids, indicating that antibody mapping
      approaches must allow for epitopes of significant size. The epitope was
      accessible in native enzyme and exposed on the cytoplasmic side, documenting the
      surface exposure of a stretch of amino acids at the N-terminus, where the Na,K
      ATPase isoforms differ most.

PMID- 9232656
TI  - Mutational analysis of the BPTI folding pathway: I. Effects of aromatic-->leucine
      substitutions on the distribution of folding intermediates.
AB  - The roles of aromatic residues in determining the folding pathway of bovine
      pancreatic trypsin inhibitor (BPTI) were analyzed mutationally by examining the
      distribution of disulfide-bonded intermediates that accumulated during the
      refolding of protein variants in which tyrosine or phenylalanine residues were
      individually replaced with leucine. The eight substitutions examined all caused
      significant changes in the intermediate distribution. In some cases, the major
      effect was to decrease the accumulation of intermediates containing two of the
      three disulfides found in the native protein, without affecting the distribution
      of earlier intermediates. Other substitutions, however, led to much more random
      distributions of the intermediates containing only one disulfide. These results
      indicate that the individual residues making up the hydrophobic core of the
      native protein make clearly distinguishable contributions to conformation and
      stability early in folding: The early distribution of intermediates does not
      appear to be determined by a general hydrophobic collapse. The effects of the
      substitutions were generally consistent with the structures of the major
      intermediates determined by NMR studies of analogs, confirming that the
      distribution of disulfide-bonded species is determined by stabilizing
      interactions within the ordered regions of the intermediates. The plasticity of
      the BPTI folding pathway implied by these results can be described using
      conformational funnels to illustrate the degree to which conformational entropy
      is lost at different stages in the folding of the wild-type and mutant proteins.

PMID- 9232657
TI  - Mutational analysis of the BPTI folding pathway: II. Effects of aromatic-
      >leucine substitutions on folding kinetics and thermodynamics.
AB  - The rates of the individual steps in the disulfide-coupled folding and unfolding
      of eight BPTI variants, each containing a single aromatic to leucine amino acid
      replacement, were measured. From this analysis, the contributions of the four
      phenylalanine and four tyrosine residues to the stabilities of the native protein
      and the disulfide-bonded folding intermediates were determined. While the
      substitutions were found to destabilize the native protein by 2 to 7 kcal/mol,
      they had significantly smaller effects on the intermediates that represent the
      earlier stages of folding, even when the site of the substitution was located
      within the ordered regions of the intermediates. These results suggest that
      stabilizing interactions contribute less to conformational stability in the
      context of a partially folded intermediate than in a fully folded native protein,
      perhaps because of decreased cooperativity among the individual interactions. The
      kinetic analysis also provides new information about the transition states
      associated with the slowest steps in folding and unfolding, supporting previous
      suggestions that these transition states are extensively unfolded. Although the
      substitutions caused large changes in the distribution of folding intermediates
      and in the rates of some steps in the folding pathway, the kinetically-preferred
      pathway for all of the variants involved intramolecular disulfide rearrangements,
      as observed previously for the wild-type protein. These results suggest that the
      predominance of the rearrangement mechanism reflects conformational constraints
      present relatively early in the folding pathway.

PMID- 9232658
TI  - Oligomerization state of S100B at nanomolar concentration determined by large
      zone analytical gel filtration chromatography.
AB  - S100B is a Ca(2+)-binding protein known to be a non-covalently associated dimer,
      S100B(beta beta), at high concentrations (0.2-3.0 mM) under reducing conditions.
      The solution structure of apo-S100B (beta beta) shows that the subunits associate
      in an antiparallel manner to form a tightly packed hydrophobic core at the dimer
      interface involving six of eight helices and the C-terminal loop (Drohat AC,
      Amburgey JC, Abildgaard F, Starich MR, Baldisseri D, Weber DJ. 1996. Solution
      structure of rat apo-S100B (beta beta) as determined by NMR spectroscopy.
      Biochemistry 35:11577-11588). The C-terminal loop, however, is also known to
      participate in the binding of S100B to target proteins, so its participation in
      the dimer interface raises questions as to the physiological relevance of dimeric
      S100B (beta beta). Therefore, we investigated the oligomerization state of S100B
      at low concentrations (1-10,000 nM) using large-zone analytical gel filtration
      chromatography with 35S-labeled S100B. We found that S100B exists (> 99%) as a
      non-covalently associated dimer, S100B (beta beta), at 1 nM subunit concentration
      (500 pM dimer) in the presence or absence of saturating levels of Ca2+, which
      implies a dissociation constant in the picomolar range or lower. These results
      demonstrate for the first time that in reducing environments and at physiological
      concentrations, S100B exists as dimeric S100B (beta beta) in the presence or
      absence of Ca2+, and that the non-covalent dimer is most likely the form of S100B
      presented to target proteins.

PMID- 9232660
TI  - Three-dimensional structures and contexts associated with recurrent amino acid
      sequence patterns.
AB  - We have used cluster analysis to identify recurring sequence patterns that
      transcend protein family boundaries. A subset of these patterns occur
      predominantly in a single type of local structure in proteins. Here we
      characterize the three-dimensional structures and contexts in which these
      sequence patterns occur, with particular attention to the interactions
      responsible for their structural selectivity.

PMID- 9232661
TI  - The first years of the Protein Data Bank.

PMID- 9232659
TI  - Cloning, purification, and preliminary characterization by circular dichroism and
      NMR of a carboxyl-terminal domain of the bacteriophage P22 scaffolding protein.
AB  - Assembly of double-stranded DNA viruses and bacteriophages involves the
      polymerization of several hundred molecules of coat protein, directed by an
      internal scaffolding protein. A 163-amino acid carboxyl-terminal fragment of the
      303-amino acid bacteriophage P22 scaffolding protein was cloned, overexpressed,
      and purified. This fragment is active in procapsid assembly reactions in vitro.
      The circular dichroism spectrum of the fragment, as well as the 1D-NMR and 15N-1H
      HSQC spectra of the uniformly-labeled protein, indicate that stable secondary
      structure elements are present. Determination of the three dimensional packing of
      these elements into the folded scaffolding protein fragment is underway.
      Structure-based drug design targeted at structural proteins required for viral
      assembly may have potential as a therapeutic strategy.

PMID- 9232662
TI  - Analysis of the cough sound: an overview.
AB  - Coughing is presented by a sudden air expulsion from the airways which is
      characterized by a typical sound. This sound is so characteristic that it allows
      identification of the cough and its distinction from other vocal manifestations.
      The cough sound is a very important symptom of well over 100 diseases and other
      conditions of medical significance. Changes in its character may have a
      considerable value in identifying the mechanisms of airway pathology present in
      respiratory diseases. The cough sound gives information about the
      pathophysiological mechanisms of coughing by indicating the structural nature of
      the tissue during therapy that leads to certain patterns of cough. Similarly the
      character of the cough sound gives information about the behaviour of the glottis
      and whether the glottis behaves differently in different pathological conditions.
      Analysis of the cough sound record has significant value in prognosis because its
      changes may indicate the effectiveness of therapy or the progress of disease.
      Despite recent progress in cough sound research the attention paid to this
      interesting physiological and clinical problem is still not sufficient to solve
      completely various open questions, including our correct knowledge of the
      mechanism of creation of cough sounds.

PMID- 9232663
TI  - Methods of recording and analysing cough sounds.
AB  - Efforts have been directed to evolve a computerized system for acquisition and
      multi-dimensional analysis of the cough sound. The system consists of a PC-AT486
      computer with an ADC board having 12 bit resolution. The audio cough sound is
      acquired using a sensitive miniature microphone at a sampling rate of 8 kHz in
      the computer and simultaneously recorded in real time using a digital audio tape
      recorder which also serves as a back up. Analysis of the cough sound is done in
      time and frequency domains using the digitized data which provide numerical
      values for key parameters like cough counts, bouts, their intensity and latency.
      In addition, the duration of each event and cough patterns provide a unique tool
      which allows objective evaluation of antitussive and expectorant drugs. Both on
      line and off-line checks ensure error-free performance over long periods of time.
      The entire system has been evaluated for sensitivity, accuracy, precision and
      reliability. Successful use of this system in clinical studies has established
      what perhaps is the first integrated approach for the objective evaluation of
      cough.

PMID- 9232664
TI  - Inhalation cough challenge in the investigation of the cough reflex and
      antitussives.
AB  - Inhalation cough challenge is a useful tool in the physiological and
      pharmacological investigation of the cough reflex. There are three types of
      challenge used, capsaicin and the vanilloids, organic acids, and distilled water
      challenge. In addition, challenge may be administered in a single dose or
      cumulative dose fashion. The correct combination of inhalation technology and
      tussive stimulus produces a sensitive and specific method for estimating the
      cough reflex.

PMID- 9232665
TI  - Cough and other reflexes on irritation of airway mucosa in man.
AB  - Both human and animal studies show that irritation of airway mucosa elicits a
      variety of reflex responses such as coughing, apnoea, and laryngeal closure. Most
      of the information concerning these reflex responses were obtained in
      anesthetized conditions with little applicability to awake conditions. Various
      aspects of cough and other reflexes on irritation of the airway mucosa are
      discussed. Studies on awake humans showed that stimulation of the laryngeal
      mucosa with a small amount of distilled water during wakefulness causes
      elicitation of the expiration reflex, cough reflex, and swallowing reflex while
      other types of responses are scarcely observed. In addition, the duration of
      these responses is remarkably short. In contrast, the same stimulation causes
      more variant, prolonged, and exaggerated responses during a light depth of
      anesthesia. An increase in depth of anesthesia abolishes expiratory efforts such
      as coughing and the expiration reflex whereas the apnoeic reflex and laryngeal
      closure reflex are resistant to the depressant effect of anesthesia. Also, the
      respiratory reflex responses to airway irritation varied, depending on the site
      of stimulation: both laryngeal and tracheal stimulation cause vigorous
      respiratory responses whereas bronchial stimulation causes little or no
      respiratory responses. These results indicate not only that the types and
      magnitude of reflex responses is greatly modified by the central nervous state
      but also that the site of stimulation is crucial for determining the pattern of
      respiratory responses elicited by airway stimulation in humans.

PMID- 9232666
TI  - Codeine, cough and upper respiratory infection.
AB  - Codeine is generally accepted as a standard or reference antitussive against
      which new antitussive medications can be compared. However there are very few
      studies which have investigated the antitussive efficacy of codeine using cough
      associated with upper respiratory tract infection (URTI) and there is little if
      any evidence to support the antitussive efficacy of codeine in this model. This
      paper discusses the mechanism of cough in man and describes some clinical
      investigations on the effects of codeine on cough associated with URTI. The
      recent clinical investigations do not provide any evidence to support an
      antitussive action of codeine in the treatment of cough associated with URTI yet
      there is evidence in the literature which indicates that codeine inhibits fictive
      cough in animal models and also has antitussive activity against both induced and
      chronic cough models in man. In order to explain these different effects of
      codeine on the different models of cough, a hypothesis is put forward that there
      are two cough pathways in man. A voluntary pathway associated with cough related
      to URTI which is not affected by codeine, and a reflex pathway associated with
      induced and chronic cough which is inhibited by codeine.

PMID- 9232667
TI  - Evaluation of antitussive agents in man.
AB  - Methodology to evaluate the efficacy of antitussive drugs rely largely on
      subjective methods and cough counts. There are few studies in cough due to
      natural disease especially using objective techniques. This paper presents data
      from a series of randomized, double blind, placebo controlled clinical trials in
      cough due to both chronic bronchopulmonary disease and acute upper respiratory
      tract infections. In these studies, cough was quantified using a standardized and
      validated computerized system for the acquisition and multidimensional analysis
      of the cough sound. Key objective parameters like cough counts, intensity,
      latency and total effort expended were studied. Guaiphenesin and bromhexine
      showed significant expectorant effects in patients with productive cough due to
      chronic bronchopulmonary disease. Differences were observed in speed of action,
      and objective and subjective measures, that probably indicate differences in drug
      action. More recently, three studies evaluated the antitussive drug
      dextromethorphan in non-productive cough due to uncomplicated upper respiratory
      tract infections. Reproducible cough suppressant effects were demonstrated after
      a single 30 mg dose using objective measures of cough counts, latency and total
      effort. These results establish the sensitivity and robustness of the cough
      quantitation methodology in the objective evaluation of cough treatments.

PMID- 9232669
TI  - The role of capsaicin-sensitive C-fibre afferent nerves in the cough reflex.
AB  - While airway rapidly adapting receptors can mediate the cough reflex, much
      evidence suggests that bronchial C-fibre receptors are also involved in guinea
      pigs and man. In man local and systemic C-fibre stimulants have a potent tussive
      action, which is blocked by low doses of local anaesthetics which leave the
      reflex bronchoconstriction intact. In guinea-pigs destruction of airway C-fibre
      receptors by large doses of capsaicin abolishes the cough reflex due to capsaicin
      and citric acid. Thus there may be subpopulations of airway C-fibres responsible
      for the different reflexes such as apnoea, cough and bronchoconstriction. The
      evidence for the role of C-fibre receptors in cough is described and discussed.

PMID- 9232668
TI  - Role of laryngeal afferents in cough.
AB  - The superior laryngeal nerve (SLN) is the main source of laryngeal afferent
      activity. A clear respiratory modulation can be noted when recording from the
      peripheral cut end of this nerve in several mammalian species. This modulation is
      due to three types of sensory endings: cold, pressure and 'drive' receptors.
      Although respiratory-modulated receptors play an important role in the function
      of the upper airway, they are not generally viewed as a primary factor in the
      elicitation of cough. Other more likely candidates for this role are thought to
      be the so-called 'irritant' endings. These are receptors that do not discharge in
      close association with the breathing cycle, but are usually silent or randomly
      active in control conditions. However, they are promptly recruited when the
      laryngeal mucosa is exposed to mechanical and/or chemical irritation. In fact,
      these receptors respond to well recognized tussigenic stimuli and are therefore
      thought to provide the triggering mechanisms for the cough reflex from the
      larynx. Endings with similar characteristics are also found in the most proximal
      areas of the tracheo-bronchial tree. On the basis of their response to irritants,
      these receptors are identified under the common denomination of 'irritant
      receptors'. However, within this category of endings we find a wide range of
      distinctive characteristics, be this in terms of responsiveness to water
      solutions of various osmolarity and composition or to particular responses to
      substances produced within the body (autacoids) or experimentally administered.

PMID- 9232670
TI  - Role of substance P in cough.
AB  - The sensory neuropeptide, substance P (SP), is present in human airway nerves,
      beneath and within the epithelium where the condensed localization of neutral
      endopeptidase (NEP), the major enzyme degrading SP, is observed. To test the
      hypothesis whether SP stimulates the cough reflex and NEP modifies the cough
      reflex, we studied the cough response to various stimuli in awake guinea-pigs.
      Inhibition of NEP with phosphoramidon caused cough, which was inhibited by
      systemic capsaicin treatment and by aerosols of a specific NK1 receptor
      antagonist FK 888. Aerosols of FK 888 also inhibited cough induced by
      bronchoconstricting agents such as acetylcholine and histamine in non-sensitized
      animals and by ovalbumin antigen in animals sensitized to ovalbumin. The number
      of coughs induced by histamine aerosols was inhibited by systemic capsaicin
      treatment and enhanced by pretreatment with a NEP inhibitor phosphoramidon.
      Likewise, FK 888 inhibited the augmented cough response to aerosolized capsaicin
      in female guinea-pigs treated with a long-term medication of an angiotensin
      converting enzyme inhibitor, cilazapril. In humans, aerosols of SP did not cause
      cough in normal subjects, whereas it did in patients with common colds. The SP
      fragment a major metabolite of SP produced by NEP, was less effective compared
      with SP in these patients, suggesting that damaged epithelium may facilitate the
      penetration of SP. These findings suggest that SP released from sensory nerves in
      response to stimuli may mediate cough and NEP may have a role in modulating SP
      induced effects.

PMID- 9232671
TI  - Tachykinin receptor antagonists and cough.
AB  - Several potent and selective antagonists for tachykinin receptors are now
      available and appear as powerful tools to investigate the physiological and
      pathological roles of tachykinins and to identify the type of receptor involved
      in their effect. Indeed, a lot of studies have shown that tachykinin NK2 receptor
      antagonists (SR 48968, MEN 10627) are able to inhibit cough induced by citric
      acid, capsaicin or allergen challenge in the unanesthetized guinea-pig or
      mechanical stimulation of the trachea in the cat. The effects of tachykinin NK1
      receptor antagonists are still debated, whereas an inhibitory effect of SR
      142801, a tachykinin NK3 receptor antagonist, has been reported against citric
      acid-induced cough in the guinea-pig. Experiments with tachykinin receptor
      antagonists which do not cross the blood brain barrier suggest that the site of
      action of tachykinin receptor antagonists is most probably peripheral, but a
      central action, at least in an area not protected by the blood brain barrier,
      cannot be excluded. Finally, tachykinin NK2 receptor stimulation seems to be
      involved in sensitisation of cough reflex.

PMID- 9232672
TI  - Modulation of cough and airway sensory fibres.
AB  - It is clear that there is still no definitive answer as to the role of RARs and C
      fibres in cough, although the evidence would appear to implicate both fibre
      types, depending on the stimulus (Fig. 2). An upregulation of the activity of
      these fibres during disease states, by the action of inflammatory mediators,
      could contribute to an enhanced cough reflex, although the possible involvement
      of central sensitization provides another exciting possibility. Whilst an
      inhibition of the activity of airway afferents should conceivably lead to an
      inhibition of the cough reflex there remain few examples where this occurs. The
      available evidence suggests that agents such as opioids and cromoglycate can act
      on C-fibres, contributing to their antitussive activity, whilst frusemide has an
      inhibitory effect, on C- and A delta-fibres, only against certain stimuli. A more
      generalized inhibition of airway sensory nerves could be achieved by ion channel
      modulators, since these might act on both myelinated and non-myelinated fibres.
      It is interesting that the only clear examples of an inhibition of sensory nerve
      activity coupled with antitussive effects are provided by sodium channel blockers
      (local anaesthetics) and a potassium channel opener (NS1619). However, it should
      be borne in mind that cough is essentially a defensive reflex, becoming
      inappropriate during disease states. It might be desirable therefore to inhibit
      only the enhanced activity of sensory nerves seen during these conditions.
      Whether this is possible awaits further information on the changes in sensory
      nerve properties during inflammation.

PMID- 9232673
TI  - Brainstem respiratory networks and cough.
AB  - The focus of this review is work that supports a model of the medullary neuronal
      network that is involved in producing the cough motor pattern of inspiratory and
      expiratory pump muscles. Evidence is presented that supports the following
      hypotheses: (1) Bulbospinal drive to respiratory motoneurons during cough arises,
      at least in part, from the same medullary neurons involved in providing drive
      during eupnoea. (2) Medullary Botzinger/ rostral ventral respiratory group
      neurons implicated in generating and shaping the eupnoeic pattern of breathing
      are also involved in producing the central cough motor pattern. The results were
      not consistent with a "cough centre" separate from the BOT/VRG. Observed neurons
      (in cats) included most of all previously identified respiratory modulated
      "types". The results showed that there were alterations in discharge patterns of
      all respiratory neurons during fictive cough. Many "types" responded as predicted
      by cough model network simulations. Based on neuron behaviours in our studies and
      inferred synaptic actions among BOT/VRG neurons, we propose a preliminary model
      for cough generation by the BOT/rVRG network.

PMID- 9232674
TI  - Role of opioidergic and serotonergic mechanisms in cough and antitussives.
AB  - This paper provides an overview of our current understanding of the serotonergic
      and opioidergic mechanisms of cough and antitussives. Systemic administration of
      8-OH-DPAT, at doses of 0.1 and 0.3 mg/kg, ip, markedly reduced the number of
      coughs in rats in a dose-dependent manner. The antitussive effects of 8-OH-DPAT,
      dihydrocodeine and dextromethorphan were significantly reduced by pretreatment
      with methysergide, but not with ketanserin. Therefore it is possible to speculate
      that 5-HT1 receptors, in particular the 5-HT1A receptors, may be more important
      than others with respect to the effect of antitussive drugs. DAMGO, a selective
      mu-opioid receptor agonist, and U-50,488H, a highly selective kappa-opioid
      receptor agonist, have potent antitussive effects when administered either icv or
      ip. However, we did not observe a cough-depressant effect of DPDPE, a selective
      delta-opioid receptor agonist. These results indicate that the antitussive
      effects of opioids are mediated predominantly by mu- and kappa-opioid receptors.
      On the other hand, naloxonazine, a selective mu 1-opioid receptor antagonist, had
      no effect on the antitussive effects associated with icv DAMGO. These results
      indicate that mu 2- rather than mu 1-opioid receptors are involved in mu-opioid
      receptor-induced antitussive affects. Antitussive effects of dextromethorphan and
      noscapine were significantly and dose-dependently reduced by pretreatment with
      rimcazole, a specific antagonist of sigma sites. However, rimcazole did not have
      a significant effect on the antitussive effect of morphine. These results suggest
      that sigma sites may be involved in the antitussive mechanism of non-narcotic
      antitussive drugs.

PMID- 9232675
TI  - Mechanisms of action of central and peripheral antitussive drugs.

PMID- 9232676
TI  - Assessment of the antitussive efficacy of codeine using cough sound pressure
      levels as a means of measuring cough.

PMID- 9232677
TI  - Effects of long-term high oxygen concentration breathing on defensive respiratory
      reflexes in guinea-pigs.

PMID- 9232678
TI  - Central 5-HT1A and 5-HT1D receptors modulate reflex bronchoconstriction in guinea
      pigs.

PMID- 9232679
TI  - The role of partial laryngeal denervation on the cough reflex in awake guinea
      pigs, rats and rabbits.

PMID- 9232680
TI  - Methods of assessing cough and antitussives in man.

PMID- 9232681
TI  - Role of the larynx in cough.

PMID- 9232682
TI  - Sensory mechanisms.

PMID- 9232683
TI  - Central nervous mechanisms in cough.

PMID- 9232684
TI  - The effect of hypoxia on the ventilatory response to carbon dioxide in man.
AB  - We used rebreathing with prior hyperventilation to measure ventilatory responses
      to CO2 at iso-oxic PO2's of 100, 80, 60 and 40 mmHg in seven subjects. The mean
      sub-threshold ventilation (S.E.) of 7.60 (1.31) L min-1 did not vary with iso
      oxic PO2. The mean peripheral-chemoreflex threshold of 41 (0.6)) mmHg PCO2 at an
      iso-oxic PO2 of 100 was greater than 39 (1.2) and 39 (0.6) at 60 and 40,
      respectively. The mean peripheral-chemoreflex sensitivity of 11.5 (5.2) L min-1
      mmHg-1 at an iso-oxic PO2 of 40 was significantly greater than 3.0 (1.3), 2.7
      (1.2) and 2.4 (1.2) at 60, 80 and 100, respectively. The mean central-chemoreflex
      threshold of 45 (1.5) mmHg PCO2 at an iso-oxic PO2 of 40 was significantly less
      than 48 (0.4) and 48 (0.7) at 80 and 100, respectively. The mean central
      chemoreflex sensitivity of 5.0 (1.1) L min-1 mmHg-1 did not vary with iso-oxic
      PO2. These findings provide insights into the control of breathing in humans,
      including the implication that CO2 must exceed its peripheral-chemoreflex
      threshold before hypoxia can effectively increase ventilation.

PMID- 9232685
TI  - Negative-impedance ventilation and pressure support ventilation: a comparative
      study.
AB  - Negative impedance ventilation (NIV) is a novel mode of assisted mechanical
      ventilation (AMV) in which the pressure support is regulated to continuously
      track inspiratory flow and/or volume. In this study, we have evaluated the
      efficacies of NIV and inspiratory pressure support (IPS) ventilation in a model
      of central airway obstruction in six rabbits. For both AMV modes there was an
      inverse relationship between the intrinsic work of breathing and alveolar
      pressure. Compared to IPS, NIV was found to: (1) achieve the same degree of
      ventilatory unloading and similar level of pulmonary ventilation with
      considerably lower alveolar pressure; (2) better restore the normal tidal volume
      and respiratory frequency; (3) yield a shorter inspiratory duty cycle, thereby
      helping to rest the respiratory muscles and preclude intrinsic positive end
      expiratory pressure. We conclude that NIV is more efficacious than IPS in
      negating airway obstruction and offers a better trade-off between the risks of
      respiratory muscle fatigue and pressure induced complications.

PMID- 9232686
TI  - Airway and tissue constrictions are greater in closed than in open-chest
      conditions.
AB  - We measured lung impedance (ZL) before and after four doses of methacholine (Mch)
      infusion in five intact chest (with esophageal balloon) and six open-chest dogs
      from 0.2 to 8 Hz with an optimal ventilator waveform. From ZL, we estimated
      airway resistance (R(aw)) and inertance (Iaw) and tissue viscance (GL) and
      elastance (HL). Two-way analysis of variance revealed that: (1) Mch had a strong
      influence on all parameters (p < 0.001), but small effect on hysteresivity, nL =
      GL/HL; (2) closed-chest GL and HL were significantly higher and Iaw lower than
      their open-chest values (p < 0.002, p < 0.05 and p < 0.0001); and (3) at the
      highest Mch dose, the relative increase in R(aw) was six times higher in the
      closed-chest condition. The reduced impact of Mch on open-chest mechanics may be
      due to constrictions superimposed on grossly different lung configurations and/or
      some humoral effects initiated by the thoracotomy. We conclude that Mch doses
      that elicit mild constriction in open-chest condition can cause a severe
      constriction in intact animals.

PMID- 9232687
TI  - Influence of thoracoabdominal pattern of breathing on respiratory resistance.
AB  - The purpose of this study was to test the hypothesis that voluntary changes in
      thoracoabdominal pattern of breathing may increase total respiratory resistance.
      Thirty-one normal subjects were asked to control their thoracoabdominal pattern
      of breathing by using a visual feedback. Thoracic and abdominal volume changes
      were measured by inductance plethysmography. Respiratory resistance and elastance
      were measured by forced oscillometry. The mean (+/-SD) percent thoracic
      contributions to tidal volume during thoracic or abdominal breathing were 75 (+/
      11) and 25% (+/-9), respectively. These changes induced small but significant
      increases in resistance (P < 0.005) and elastance (P < 0.002). The increased
      resistance was observed in 22 subjects for thoracic breathing (P < 0.016) and in
      21 subjects for abdominal breathing (P < 0.043). The mean value (+/-SD) of
      individual increases in resistance during thoracic or abdominal breathing,
      compared with normal breathing, were 9.2 +/- 17.5 and 9.4 +/- 19.9%,
      respectively. The fact that departing from spontaneous pattern increases
      respiratory resistance is consistent with the notion that breathing pattern is
      optimally adjusted on the basis of mechanical criteria.

PMID- 9232688
TI  - Influence of external loading and assisted ventilation on chest wall mechanical
      properties.
AB  - Instantaneous respiratory effective elastance (Eteff) and tissue resistance (Rt)
      may be measured by studying the relationship between flow at the airway opening
      and at the chest during forced oscillations; using that method it has been shown
      that Rt varies little during breathing while Eteff presents much larger phasic
      variations than can be explained by the curvature of the static pressure-volume
      curve (Tomalak et a1., 1997). The aim of this study was to test the hypothesis
      that the large variations of Eteff were related to the activity of respiratory
      muscles. For this, we studied in six healthy subjects the changes in Eteff and Rt
      induced by inspiratory and expiratory elastic loading (IEL and EEL,
      respectively), resistive loading (REL) and assisted ventilation (ASV) while
      keeping lung volume, ventilation and breathing pattern as constant as possible.
      IEL and EEL predominantly increased Eteff during the inspiratory and expiratory
      phases, respectively; in contrast, ASV decreased Eteff during inspiration and
      almost completely abolished its positive volume dependence. The changes of Rt
      usually paralleled those of Eteff. We conclude that respiratory muscle activity
      is responsible for most of the variations of Eteff during spontaneous breathing.

PMID- 9232689
TI  - Tachykinins do not cause plasma leakage in the rabbit trachea.
AB  - The aim of this study was to determine if neuropeptides mediate increases in
      airway microvascular leakage in the rabbit. New Zealand white rabbits were
      anaesthetised and challenged with either capsaicin (50 mg/kg s.c. or i.p.) or
      substance P (10(-3) or 10(-4) nebulised or 1 microgram/kg i.v.) or vagally
      stimulated with a range of pulse trains (5-15 Hz, 5-15 V, 0.2-2 msec).
      Microvascular leakage was assessed using the Evans blue dye technique. A further
      two groups of rabbits were challenged with nebulised metabisulphite (100 mg) or
      phosphate buffered saline to serve as positive and negative controls. Challenge
      with capsaicin, substance P or vagal stimulation did not significantly increase
      tracheal or bronchial Evans blue concentrations above negative control levels. We
      conclude that neuropeptides do not mediate increases in microvascular leakage in
      the major airways of the rabbit.

PMID- 9232690
TI  - The inhibitory effect of fluoride on carbachol-induced bovine bronchial
      contraction.
AB  - The effect of sodium fluoride (NaF) on the responsiveness of airway smooth muscle
      was investigated in bovine bronchial segments. NaF (0.5-10 mM) induced a delayed
      concentration-dependent active pressure (AP) and reduced the lactate
      concentration in the solution. Pyruvate (10 mM) increased the NaF-induced
      contraction. There was a 50 +/- 7% decrease in carbachol (10 microM)-induced AP
      when bronchi were pretreated with NaF (5 mM) and a 37 +/- 9% decrease when NaF (5
      mM) was added during the maintained carbachol-induced contraction. These
      inhibitory effects were enhanced by KCN and hypoxia. When bronchi were pre
      incubated with 10 microM verapamil, a calcium channel inhibitor, the contractile
      effect of 5 mM NaF was reduced to 8 +/- 3% of the control. PKC activity in
      bronchial smooth muscle was significantly increased by NaF (5 mM). Staurosporine
      (30 nM) abolished the contractile effect of NaF. These results suggest that: (1)
      NaF either contracts or relaxes bronchial smooth muscle depending on the
      experimental conditions; (2) the relaxing effect is related to the inhibitory
      action of NaF on glycolysis; (3) the contractile effect of NaF is possibly
      mediated by modulation of a calcium channel via a PKC-dependent pathway; (4)
      carbachol-induced contraction is glycolysis pathway dependent in the absence of
      NaF but switches to oxidative dependent in its presence.

PMID- 9232691
TI  - Histamine-evoked acetylcholine release in sensitized tracheal preparation.
AB  - The contractile response to histamine of tracheal muscle was studied in
      preparations from BSA-sensitized and non-sensitized guinea-pigs. Sensitization
      did not enhance the overall response to histamine. However, this response showed
      evidence of acetylcholine participation. In sensitized preparations, atropine
      (0.1 microM) caused a significant depression of the dose response to histamine (n
      = 11, p = 0.028), especially in the range 2-8 microM. Physostigmine (0.1 microM)
      significantly potentiated the effect of histamine (n = 8, p = 0.003), especially
      at greater than 4 microM histamine. The response to histamine of non-sensitized
      preparations was not altered by atropine (n = 11) or physostigmine (n = 8). The
      following agents did not discriminate between sensitized and non-sensitized
      preparations: Famotidine, an H2 antagonist; dimaprit, an H2 agonist;
      thioperamide, an H3 antagonist; alpha-methylhistamine, an H3 agonist; gallamine,
      an M2 antagonist, suggesting that muscarinic M2 receptor dysfunction alone is not
      sufficient to cause bronchial hyper-responsiveness. The results show that
      sensitization causes a change in the components of the contractile response to
      histamine rather than bronchial hyper-responsiveness to this agent.

PMID- 9232692
TI  - Na+/K+ ATPase mediates rhythmic spontaneous relaxations in canine airway smooth
      muscle.
AB  - In canine airway smooth muscle, cyclopiazonic acid (CPA; selective blocker of the
      sarcoplasmic reticulum Ca(2+)-pump) evokes a contractile response which is
      initially mediated via release of internally sequestered Ca2+, but is later
      supported almost exclusively by electromechanical coupling. As such, this second
      component is highly sensitive to inhibition of voltage-dependent Ca(2+)-influx
      (e.g. dihydropyridines, removal of external Ca2+) or to membrane
      hyperpolarization. In the present study, we describe relaxations which occur
      spontaneously during this second component of the CPA-evoked contraction. These
      relaxations are also electromechanically mediated, since they are abolished by
      depolarization of the membrane by high-K+ media. TEA has relatively little effect
      on the phasic activity, thus ruling out an involvement of Ca(2+)-dependent K+
      channels. On the other hand, the phasic activity is abolished by ouabain, by
      removal of external K+, or by cooling and is markedly slowed by removal of
      external Na+. These observations indicate that the phasic activity is mediated by
      the Na+/K(+)-ATPase.

PMID- 9232693
TI  - Treatment of segmental defects in long bones using osteopromotive membranes and
      recombinant human bone morphogenetic protein-2. An experimental study in rabbits.
AB  - The purpose of this study was to investigate whether barrier membranes that were
      earlier shown to promote bone healing in the craniofacial skeleton are capable of
      producing bone healing in long bone. defects by themselves or in combination with
      recombinant human bone morphogenetic protein 2 (rhBMP-2). Segmental defects (10
      mm long) in the rabbit radius, known to heal as pseudoarthrosis-like defects,
      were used as the experimental model. Treatment with expanded
      polytetrafluoroethylene membranes (GORE-TEX Membrane) (n = 10) resulted in only
      minor amounts of bone formation within the defect and collapse of the membranes
      was common. When placement of membranes was combined with implantation of rhBMP-2
      in a beaded biodegradable copolymeric PLA/PGA carrier, total bony bridging of the
      defects was accomplished within 10 weeks (n = 5). Osteopromotive membranes
      combined with mBMP-2 can therefore bring about complete healing of long bones.
      The membranes exclude soft tissue from the defect and at the same time keep the
      growth-stimulatory implant in place and maintain the anatomical contour of the
      bone. The combination of osteopromotive membranes and rhBMP-2 may be of. value in
      reconstructive bone surgery.

PMID- 9232695
TI  - Analysis of nuclear DNA and morphometry, and proliferating cell nuclear antigen
      in primary and metastatic malignant melanoma.
AB  - Sections from 23 primary malignant melanomas and 39 corresponding metastases were
      analysed for DNA content, nuclear morphometry, and proliferating cell nuclear
      antigen (PCNA). In 15 of 23 patients (65%) both primary and secondary tumours
      showed similar DNA patterns, whereas a disparity was found in the remaining eight
      patients (35%). The 23 primary tumours and groups of metastases (from different
      patients) located in skin, lymph nodes, and brain did not differ significantly in
      any of the variables investigated. Cox stepwise regression analysis indicated
      that a large variability (CV) of nuclear area in the first metastasis correlated
      with increased survival after recurrence (p = 0.039) as well as with survival (p
      = 0.031).

PMID- 9232694
TI  - The effect of diclofenac (Voltaren) on the contraction of collagen lattices.
AB  - The inhibition of prostaglandin synthesis by diclofenac was studied with regard
      to effects on connective-tissue contraction and on the chemotaxis of fibroblasts
      stimulated by platelet-derived growth factor type BB (PDGF-BB). Collagen lattices
      populated with human fibroblasts responded to diclofenac with significantly
      increased contraction; the peak effect occurred at a dose of 5 micrograms/ml.
      Using a two-chamber system, PDGF-BB significantly increased the chemotactic
      activity of fibroblasts, and addition of diclofenac further increased this
      activity. Higher doses of diclofenac resulted in cell death, which was also
      reflected in lessened contraction of lattices with 50 micrograms/ml diclofenac,
      half of the cells were dead. The study showed that inhibition of prostaglandin
      synthesis by diclofenac increases the contraction of collagen lattices populated
      with human fibroblasts and increases the chemotactic activity of fibroblasts
      stimulated with PDGF-BB.

PMID- 9232696
TI  - Heparin-chitosan complexes stimulate wound healing in human skin.
AB  - The effect of heparin ionically linked to chitosan on the stimulation of re
      epithelialisation of full thickness wounds in human skin was investigated in an
      in vitro model. After seven days of incubation, heparin-chitosan gel stimulated
      9/10 of the full thickness wounds to re-epithelialise compared with only 3/10 of
      the wounds that were covered with chitosan gel or membrane, and none of the
      wounds incubated without gel or membrane or with heparin solution alone. Both
      dermal and epidermal cells were viable after the incubation time. Furthermore,
      the stimulatory effect of the heparin-chitosan complexes depended on the
      concentration of heparin in the complex. We hypothesise that these effects are
      caused by stabilisation and activation of growth factors that bind to immobilised
      heparin.

PMID- 9232697
TI  - Clinical appearance of spontaneous and induced first and second branchial arch
      syndromes.
AB  - The clinical appearance was investigated of 29 patients with mandibulofacial
      dysostosis, 26 with hemifacial microsomia, and seven with thalidomide-induced
      malformations affecting derivatives of the first and second branchial arches.
      Malformations of the external ear, ear canal, middle ear, zygoma, maxilla,
      mandible, and lower eye lid were prominent features of the syndromes. Facial
      nerve and 6th cranial nerve paralysis as well as anophthalmia or microphthalmia
      were seen only in patients with hemifacial microsomia and in the thalidomide
      induced syndrome. We compared the clinical results with those in an animal model
      in which an induced first and second branchial arch syndrome depends on disturbed
      migration of neural crest cell during early embryogenesis. The critical time for
      a similar process in humans would be between the 20th and 29th days of pregnancy.

PMID- 9232698
TI  - Complete reduction of lymphoedema of the arm by liposuction after breast cancer.
AB  - The incidence of lymphoedema of the arm after mastectomy ranges between 8% and
      38%, and it is an appreciable problem from both functional and social aspects.
      Conservative and previous surgical regimens have not been completely successful.
      In the light of these experiences, liposuction clearly constitutes an interesting
      new surgical approach, which is potentially capable of effecting predictable and
      reliable improvements in patients with lymphoedema. Twenty eight women with
      lymphoedema of the arm after breast cancer were consecutively treated by
      liposuction. Limb compression with a compression garment was instituted
      immediately after operation. All patients had been given radiotherapy after the
      operation for breast cancer. Mean preoperative volume of oedema was 1845 ml
      (range 570-3915), and mean volume of aspirate was 2250 ml (range 1000-3850);
      volume of aspirate correlated linearly with the volume of preoperative oedema.
      There were no major surgical complications, but blood transfusion was necessary
      in eight patients whose volume of aspirate exceeded 2000 ml. After 12 months (n =
      24), an average reduction in volume of oedema of 106% was found. Such a
      normalisation can be expected in patients with oedema that amounts to about 2500
      ml. Although the oedema cannot be completely removed in more severe cases,
      substantial reduction is beneficial from both functional and cosmetic aspects. We
      conclude that liposuction is safe and effective for reducing lymphoedema of the
      arm after operations for breast cancer. In a one-stage procedure, oedematous and
      hypertrophic fat tissue can be removed with an excellent clinical outcome.

PMID- 9232699
TI  - Percutaneous sclerotherapy of venous malformations of the head and neck using
      sodium tetradecyl sulphate (sotradecol).
AB  - Thirty-eight patients with venous malformations of the face, neck, and tongue
      underwent percutaneous sclerotherapy with direct puncture and instillation of
      sodium tetradecyl sulphate (Sotradecol) (33-67% solution, mixed with contrast
      material) into the lesions. Each patient underwent from one to seven treatment
      sessions (mean 2.2), followed by reconstructive surgery in three cases. Of the 34
      patients who responded to the follow-up questionnaire, the late results were
      excellent or good in 23 patients (68%), moderate in eight, unchanged in three,
      and were worse in one. Compared with our previous experience of embolisation of
      such malformations with ethanol, the results with Sotradecol were slightly worse.
      There was one serious complication, unilateral loss of vision in a patient with a
      large malformation that extended to the orbit. In conclusion, percutaneous
      sclerotherapy with Sotradecol is effective treatment for venous malformations of
      the head and neck. Careful planning is essential to reduce the risks of the
      treatment.

PMID- 9232700
TI  - Treatment of keloid and hypertrophic scars by iontophoretic transdermal delivery
      of tranilast.
AB  - The feasibility of iontophoretic transdermal delivery of tranilast (N-(3,4
      dimethoxycinnamoyl) anthranilic acid) for the treatment of keloid and
      hypertrophic scars was evaluated in hairless rats and humans. A drug electrode
      containing tranilast 1.5 ml (8 mg/ml in ethanol/water (8/2, v/v) mixture) was
      placed on the dorsal skin surface of anaesthetised rats or the affected parts of
      patients, and connected to the negative pole; an electric current (0.5-4 mA for
      rats, 2 mA for people) was pulsed through at one minute intervals. Tranilast was
      effectively delivered transdermally iontophoretically into the restricted skin
      tissues of hairless rats and the affected parts of four patients with
      hypertrophic scars with no skin damage. In four other patients tranilast given
      iontophoretically for a period of 30 minutes a week reduced the patients'
      complaints of pain and itching after only one or two treatments although there
      were some variations among patients. These results indicate that the transdermal
      iontophoretic delivery of tranilast is a useful treatment for keloid and
      hypertrophic scars, particularly for relieving pain and itching, and is more
      beneficial than tranilast given orally.

PMID- 9232701
TI  - Closed reduction and external fixation of unstable fractures of the distal
      radius.
AB  - The anatomical and functional outcome and complications after closed reduction
      and external fixation of unstable fractures of the distal radius were reviewed in
      29 patients. The fractures were reduced by longitudinal traction and closed
      manipulation under fluoroscopic control, and the reduced position was retained by
      a standard half-frame Hoffmann external fixator for six to eight weeks. The mean
      follow-up time was four (3-7) years. The reduction failed in three patients after
      too early removal of the fixator (three to five weeks). For the rest of the
      patients the dorsal angulation, the radial length, the articular step-off, and
      the intra-articular gap between fragments were significantly improved. Twenty-two
      patients had excellent or good anatomical alignment and in seven it was fair. One
      patient had a superficial pin infection, six patients had transient
      paraesthesias, and one patient transient mild dystrophia. At follow-up one
      patient had some finger stiffness; this was the only persistent complication. The
      median Gartland and Werley functional score was 3. The functional end result was
      excellent or good in 22 patients, fair in four, and poor in three.

PMID- 9232702
TI  - Timing of free microsurgical tissue transfer for the acute phase of hand
      injuries.
AB  - Because of favourable survival rates in replantation surgery and a high standard
      of free tissue transfer the interval between injury and microsurgical
      reconstruction has become gradually shorter. The acute phase can be defined as
      the interval ranging from emergency procedures within 24 hours to urgent
      procedures done within 72 hours. Bearing in mind the infection rates that have
      been reported of 1.5% for the acute phase and 17.5% for the late phase, we should
      encourage emergency reconstructions. However, in most cases of upper extremity
      injuries, reconstruction with conventional flaps is possible. Between 1981 and
      1995 we did 72 acute post-traumatic free tissue transfers to the upper extremity
      in our unit within 72 hours (urgently). There were no significant differences in
      the incidence of infections when acute were compared with urgent procedures. As a
      result we support the concept of urgent operations. The following advantages are
      to be considered: urgent operations allow a second look operation, the viability
      of the extremity can be assessed, and the reconstructive procedure can be planned
      more precisely. Last but not least, the procedure is done during the day time
      with better operating conditions.

PMID- 9232703
TI  - Bilateral fast magnetic resonance imaging of the operated carpal tunnel.
AB  - Our aim was to quantify the structural changes of the carpal tunnel including
      area and volume after surgical release. We studied 28 patients who underwent 31
      operations for carpal tunnel syndrome (CTS), mean age 54.7 years (range 32-78).
      All had abnormal nerve conduction studies. Magnetic resonance imaging (MRI) of
      both wrists was done before and after operation using two fast imaging sequences,
      turbo spin echo (TSE) and fast field echo (FFE). The same surface coils and
      parameters were used in both instances. With a computerised analyser we
      calculated the volume of the whole tunnel from inlet to outlet before and after
      operation and the wrist volume:carpal tunnel volume ratio. The intensity of the
      magnetic resonance signal emitted by the median nerve was assessed in all wrists
      before and after operation. The mean (SD) volume of the tunnel in 31 wrists with
      CTS was 11511.7 (2857) mm3 before and 13803.4 (3034.9) mm3 after operation (p =
      0.0001). The mean (SD) relative signal intensity of the median nerve was 1.7
      (1.8) preoperatively and 1.3 (1.1) postoperatively (p = 0.19). Other
      postoperative changes included persistent nerve enlargement (n = 21),
      misalignment of the tendons (n = 20), fibrous tissue deposits (n = 20), fat
      tissue deposits (n = 21), and muscle oedema (n = 6). The modifications of the
      carpal canal as a consequence of open surgical release (including increased
      volume and displacement of the flexor tendons) argue for the use of an endoscopic
      procedure in the treatment of CTS.

PMID- 9232704
TI  - Dermal leiomyosarcoma of the right fifth finger. Case report.
AB  - A 17 year old man presented with a five-month history of swelling of the distal
      phalanx and a small ulcer on the pulp of the right fifth finger. Despite biopsy
      the diagnosis was missed until more than six months after onset, when the lesion
      was excised and histological examination showed a dermal leiomyosarcoma.

PMID- 9232705
TI  - Transfer of the second toe to the hand in a patient with Monckeberg's sclerosis.
AB  - We present a case of second toe to hand transfer in a 64 year old patient with
      Monckeberg's sclerosis, who had had first four fingers of his right hand
      amputated. The result was satisfactory, even though this type of arteriosclerosis
      is usually considered a relative contraindication to transfer.

PMID- 9232706
TI  - Practice variation in Swedish primary care.
AB  - OBJECTIVE: To study individual practice patterns of physicians working in primary
      health care for standardized simulated cases on their first visit, and relate
      them to resource consumption for diagnostic tests, drugs and sick leave from a
      combined perspective of the health care and social security systems. DESIGN:
      Postal questionnaire presenting six hypothetical working-age cases with symptoms
      of ailments common in primary care asking physicians to order diagnostic tests
      and procedures, drugs, follow-up appointments and sick pay. SETTING: Swedish
      primary health care centres. SUBJECTS: Two hundred randomly selected physicians.
      MAIN OUTCOME MEASURES: Activities taken by the physician-diagnostic and
      laboratory tests ordered, drugs prescribed, length of sick leave and the cost of
      these actions. RESULTS: Practice patterns varied considerably, corresponding to a
      six-fold difference in total cost between the "cheapest" and "most expensive"
      physician. The largest share was loss of production as estimated by the cost of
      prescribed sick leave. Physicians who practised further away from hospitals and
      those who had worked more years tended to prescribe more measures. However, this
      only explained a small portion of the observed variation, which may be due to
      different physician attitudes to taking risks. CONCLUSION: "Paper" cases of
      common medical ailments presented to primary care physicians revealed
      considerable differences in practice style, resulting in six-fold differences in
      cost of measures prescribed at first visits.

PMID- 9232707
TI  - Working conditions and family situation in relation to functional
      gastrointestinal disorders. The Swedish Dyspepsia Project.
AB  - OBJECTIVE: To examine whether improvement and/or deterioration of functional
      gastrointestinal symptoms relate to psychosocial factors, and whether patients
      with such symptoms have special characteristics with regard to working
      environment in comparison to a referent population. DESIGN: Multicentre,
      prospective study of consecutive patients seeking medical advice at health
      centres for gastrointestinal symptoms. SETTING: Several municipalities in Sweden:
      Vanersborg, Trollhattan, Tibro, Alfta, Borensberg, Malmo, Kungalv, Hudiksvall,
      Vadstena, and Sandviken. PARTICIPANTS: 615 patients, aged 18-81 years, who after
      medical examination, upper endoscopy and laboratory test were defined as having
      functional gastrointestinal disorders. MAIN OUTCOME MEASURES: Initial
      characteristics and response to treatment according to a 5-graded symptom score
      as obtained from a psychosocial questionnaire collected during and at the end of
      a four-week treatment period. RESULTS: Patients with functional gastrointestinal
      disorders differed from a referent population of actively employed women and men
      in the county of Stockholm. They felt less possibility to influence their working
      conditions. Shift workers were also overrepresented. Psychosocial background
      factors had an effect on improvement of symptoms during four weeks of treatment.
      There were some differences between men and women. For women, working hours and
      home circumstances were important. After four weeks women who worked part-time
      felt better than those who worked full-time. Married women made a better recovery
      than single women. For men, working conditions had a greater effect on recovery.
      Those who felt that they received support from their colleagues at work improved
      to a greater extent than the other men.

PMID- 9232708
TI  - Diagnostic methods in dyspepsia: the usefulness of upper abdominal ultrasound and
      gastroscopy.
AB  - OBJECTIVES: To examine the diagnostic value of gastroscopy and upper abdominal
      ultrasound, which are frequently used as primary tests in dyspeptic patients in
      general practice. To test the influence of age for accuracy of both diagnostic
      methods. DESIGN: Clinical study. SETTING: Four health centres in Kuopio Province,
      Finland. SUBJECTS: Four hundred unselected consecutive dyspeptic patients (91
      less than 45 years of age) who consulted their general practitioners. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive
      values (PV), efficiency and usefulness index (UI) were calculated for upper
      abdominal ultrasound and for gastroscopy in detecting the causes of dyspepsia in
      primary care. Final diagnosis was determined after one year follow-up. RESULTS:
      The sensitivity of upper abdominal ultrasound in detecting the cause of dyspepsia
      was 0.07, the specificity 0.91, PV+ 0.36, PV- 0.56, and UI -0.001. Ultrasound was
      not more efficient in older patients. Gastroscopy was the most efficient method
      with a sensitivity of 0.75, specificity 1.00, PV+ 0.99, PV- 0.83 and UI 0.56. The
      usefulness of gastroscopy was even better among patients over 45 years of age.
      CONCLUSIONS: The usefulness of upper abdominal ultrasound is low regardless of
      patient's age. Gastroscopy is superior to upper abdominal ultrasound as a first
      line diagnostic method in diagnosing dyspepsia, especially among patients over 45
      years of age.

PMID- 9232709
TI  - Starting insulin therapy in elderly non-insulin-dependent diabetic patients at a
      health care centre. Methodological and economic aspects.
AB  - OBJECTIVE: To try to start insulin therapy in elderly non-insulin-dependent
      diabetes mellitus (NIDDM) patients with secondary failure in primary health care,
      and compare costs for starting treatment in a health care centre and in a day
      care clinic in a hospital. DESIGN: Time and costs for start of insulin were
      calculated. SETTING: A health care centre in Stockholm, Sweden. SUBJECTS:
      Fourteen consecutive patients in the health care centre and a control group of 14
      patients in the day-care clinic. RESULTS: Metabolic control in both groups
      improved significantly. Total time spent with the district nurse to start insulin
      treatment was 3 hours during about 7 weeks with a total cost of SEK 1100 in the
      health care centre. In the day-care clinic patients were admitted 5.6 days with a
      total cost of SEK 6100-10900. CONCLUSIONS: Elderly patients can learn the
      injection technique and manage insulin therapy, which results in good metabolic
      control. Insulin treatment can be started in primary health care. With elderly
      patients it takes time, but it is far more cost-effective in primary health care
      than at the hospital.

PMID- 9232711
TI  - Quality of life in diabetic patients registered with primary health care services
      in Sweden.
AB  - OBJECTIVE: To evaluate the health-related quality of life in diabetic subjects in
      primary health care. DESIGN: A cross-sectional, questionnaire survey of diabetic
      patients registered with primary health services, compared with a standard
      population sample. SETTING: Three community health centres in the Metropolitan
      Stockholm area. SUBJECTS: 341 diabetic individuals aged 21-84 years, with 229
      respondents, i.e. 67%. Matched controls of the same age and sex from a standard
      population sample of 2366 individuals. MAIN OUTCOME MEASURES: Quality of life was
      assessed by the Swedish Health-Related Quality of Life Survey (SWEDQUAL), adopted
      from the Medical Outcomes Study and consisting of 61 items covering aspects of
      physical, mental, social, and general health. Medical data were extracted from
      the medical records. RESULTS: Diabetic patients had significantly lower scores on
      all scales (p < 0.001 for ten, and p < 0.01 for one), except for social health,
      when compared with the standard population sample. Outcomes were correlated with
      vascular and non-vascular comorbidity, age, and income, but not with level of
      metabolic control. CONCLUSIONS: Diabetic patients in primary health care have a
      markedly lower health-related quality of life, compared with a standard
      population.

PMID- 9232710
TI  - A model for quality assessment in primary health care using the tracer condition
      technique with insulin treated diabetes as one of the tracers.
AB  - OBJECTIVE: To find a method for quality assessment in primary health care and to
      apply this method on a defined disease. DESIGN: General practitioners and
      hospital doctors worked out a programme for evaluating the quality of outpatient
      care of patients with insulin treated diabetes as one of five tracers. An expert
      committee comprising experienced general practitioners and hospital doctors
      compared two health centres with one outpatient medical department. Data were
      collected during a defined period combined with a one-year retrospective view,
      official statistics on medical care, and a questionnaire completed by the
      patients. SETTING: Two primary health care centres and one outpatient medical
      department in southwestern Sweden. PATIENTS: 243 insulin treated diabetic
      patients attending the hospital and 87 insulin treated patients attending the
      health centres. MAIN RESULTS: There were no difficulties for the expert panel to
      agree on which indicators were to be studied. The expert panel concluded that
      there was no difference between the quality of the two levels of care studied.
      CONCLUSIONS: Medical audit was a useful method for evaluating medical quality. Co
      operation between hospital doctors and general practitioners was of great value
      for evaluation of the quality of primary health care.

PMID- 9232712
TI  - Drug prescribing during direct and indirect contacts with patients in general
      practice. A report from the More & Romsdal Prescription Study.
AB  - OBJECTIVE: To describe general practitioners' (GPs) prescribing patterns during
      direct contacts (DC) vs. indirect contacts (IC) with respect to the patients (age
      and sex), diagnoses, and drugs. DESIGN: Descriptive study. SETTING: In the
      Norwegian county More & Romsdal, the GPs recorded all contacts with patients and
      prescriptions during two months. SUBJECTS: 69843 contacts with patients (42202
      DC; 24983 IC) during which 56758 prescriptions were issued. MAIN OUTCOME
      MEASURES: Prescriptions (drugs, strength of tablets, amount prescribed,
      initial/repeat). Diagnoses for prescribing. RESULTS: 72 drugs were prescribed per
      100 DC; 93 per 100 IC. The drugs prescribed most frequently during DC were CNS
      drugs (19%), antibiotics (18%), and respiratory drugs (14%); and during IC, CNS
      drugs (34%), cardiovascular (16%), and respiratory drugs (12%). More
      prescriptions during IC were repeat (IC, 79%; DC, 37%). 57% of all CNS-drugs were
      issued during IC (90% of which were repeat prescriptions). 25% of the antibiotics
      were issued during IC (70% of which were initial prescriptions). CONCLUSION: The
      GPs' prescribing patterns during DC and IC are different, which probably reflects
      that different health problems are handled during DC and IC. Prescription studies
      should address both settings. Our findings raise concern about the medical
      foundation for antibiotic and psychotropic prescribing during IC.

PMID- 9232713
TI  - Impact of postal invitations and user fee on influenza vaccination rates among
      the elderly. A randomized controlled trial in general practice.
AB  - OBJECTIVE: To examine the impact of postal invitations and user fee on influenza
      vaccination rates. DESIGN: A controlled randomized trial in 13 general practices.
      One third of the participating patients received postal invitations to influenza
      vaccination free of charge. Another third received postal invitations to
      influenza vaccination on paying the usual fee (US$ 40-60). The last third served
      as a control group, being vaccinated at their own request and paying the usual
      fee. SETTING: General practice in the Counties of Funen and Vejle, Denmark.
      PATIENTS: Five hundred and eighty-five patients aged 65 years or older,
      recognized by their general practitioner (GP) as being in the risk group for whom
      influenza vaccination is recommended. MAIN OUTCOME MEASURES: Influenza
      vaccination rates. RESULTS: In the control group 25% (19-31%, 95% confidence
      interval) of the patients were vaccinated, compared with 49% (42-56%) in the
      group who received a postal reminder and paid the usual fee, and 72% (65-78%) in
      the group invited to be vaccinated free of charge. CONCLUSION: It is suggested
      that GPs send postal invitations to their elderly patients in the risk groups
      urgently recommending influenza vaccination. Attention should also be given to
      offering free influenza vaccination to elderly patients who have recognized
      indications for vaccination.

PMID- 9232714
TI  - Social insurance for health service.
AB  - Implementation of social insurance for financing health services has yielded
      different patterns depending on a country's economic level and its government's
      political ideology. By the late 19th century, thousands of small sickness funds
      operated in Europe, and in 1883 Germany's Chancellor Bismarck led the enactment
      of a law mandating enrollment by low-income workers. Other countries followed,
      with France completing Western European coverage in 1928. The Russian Revolution
      in 1917 led to a National Health Service covering everyone from general revenues
      by 1937. New Zealand legislated universal population coverage in 1939. After
      World War II, Scandinavian countries extended coverage to everyone and Britain
      introduced its National Health Service covering everyone with comprehensive care
      and financed by general revenues in 1948. Outside of Europe Japan adopted health
      insurance in 1922, covering everyone in 1946. Chile was the first developing
      country to enact statutory health insurance in 1924 for industrial workers, with
      extension to all low-income people with its "Servicio Nacional de Salud" in 1952.
      India covered 3.5 percent of its large population with the Employees' State
      Insurance Corporation in 1948, and China after its 1949 revolution developed four
      types of health insurance for designated groups of workers and dependents. Sub
      Saharan African countries took limited health insurance actions in the late 1960s
      and 1970s. By 1980, some 85 countries had enacted social security programs to
      finance or deliver health services or both.

PMID- 9232715
TI  - Weak and strong holism.
AB  - Dissatisfaction with the health care system, in combination with an increasing
      academic status of paramedical professions, is currently inspiring the analysis
      of central medical terms by philosophers. One interesting result is the
      formulation of equilibrium theories that define health without reference to
      disease. It is argued here that the alleged holism of such theories is in fact
      weaker than the strong holism represented by the irreductive materialism inherent
      in traditional medicine. Strong holism resolves certain anomalies in the weakly
      holistic description of the Human Being, notably the claim that perfect health is
      compatible with having a deadly disease.

PMID- 9232716
TI  - Pitfalls in epidemiological analysis.
AB  - Epidemiologists rely heavily on the relative risk in their analyses and
      presentations. As an index it is intelligible and intuitively appealing but can
      give an exaggerated impression of the strength of the association and is
      unreliable for comparisons. This can be shown by deriving relative risks from a
      normal correlation surface with an unimpressive level of correlation. Relative
      risks ought to be handled with caution; the underlying population risk and the
      relative size of exposed and reference categories should be reported. Efforts to
      control for additional variables, confounders, by some kind of multi-variate
      technique, another standard procedure, could easily give a false sense of
      security. From time to time it has been made clear in the literature that errors
      of measurement in the third variable or in the additional variables could lead to
      the appearance of false independent effects, but these warnings do not seem to
      have been heeded nearly as much as they deserve. A simulation experiment is used
      to bring the lesson home, with realistic numerical assumptions. A moderate degree
      of error contamination will produce spurious effects. This has nothing to do with
      sampling errors, large samples rather aggravate this danger. In meta-studies this
      is a source of error and conflicting results to take account of.

PMID- 9232717
TI  - Why was the perinatal mortality rate higher in Denmark than in Sweden? The
      development in the 1970s and 1980s.
AB  - The purpose of this article is to identify factors explaining why the perinatal
      mortality rate ceased to fall in Denmark during the 1980s, while it continued to
      do so in Sweden, and to study the ability of known risk factors to predict this
      development. My analysis is based on routinely collected published data on all
      births, where I have studied the levels and changes in known risk factors for
      perinatal deaths in the two countries. The results of the study are: The
      proportion of low birth weight infants and the mothers' age and parity did not
      differ or change in a way that explains the higher perinatal mortality rate in
      Denmark during the 1980s. The weight specific perinatal mortality rate was the
      same in the two countries, with the exception of very low birth weight babies,
      i.e. below 1,500 grammes, where the perinatal mortality rate was higher in
      Denmark; this difference increased during the 1980s. The proportion of very low
      birth weight infants increased in Denmark from the 1970s to the 1980s while it
      remained stable in Sweden. The Danish increase in the proportion of low birth
      weight infants can be due to changed registration practices with more very small
      infants being registered in the 1980s. Among the factors studied registration
      practices, smoking and neonatal care seemed to be able to explain part of the
      differences between the two countries. The relative risk of perinatal death
      associated with the mothers' age and parity varied depending on the size of the
      groups at risk: the more women in high age and parity groups the lower the
      relative risk, which indicates that a selection as well as a causal effect was
      present. A conclusion is that the changes in relative risk over time associated
      with age and parity should lead to a closer investigation of the characteristics
      actually associated with an increased risk in order not to treat all old and
      multiparous women as patients at risk.

PMID- 9232718
TI  - Health-related social mobility: a comparison of currently employed men and women
      in Britain and Finland.
AB  - Selective health-related social mobility has been suggested as one possible
      explanation for health inequalities. The aim of this paper is to examine the size
      and significance of the contribution which health-related social mobility makes
      to social class differences in health. We do this by examining the association
      between intergenerational social mobility and health among currently employed men
      and women in Britain and Finland. We used comparable nationally representative
      interview surveys from Britain and Finland. The British data is derived from the
      General Household Survey for 1988 and 1989, and the Finnish data from the 1986
      Survey on Living Conditions. Health measures included limiting long-standing
      illness and self-assessed health as below good. Social mobility was measured
      comparing the respondent's class of origin (father's occupation) with his/her
      class of destination (own current occupation). Social structural changes and
      related social mobility have been more dramatic in Finland than in Britain during
      the last few decades. Downward mobility has been relatively rare, and mobility
      has taken place predominantly upwards. In Finland downward mobility from upper
      non-manual to manual worker was associated with a somewhat higher risk of
      limiting long-standing illness than expected among men as well as women. However,
      there was no statistically significant interaction effect on health between the
      respondent's father's occupational class and his/her own current class. In
      Britain, neither self-assessed health nor limiting long-standing illness were
      related to social mobility. Some weak evidence for health-related downward social
      mobility was found for currently employed Finnish men and women, but not for
      their British counterparts. Moreover, the evidence is weaker for self-assessed
      health than for limiting long-standing illness. Where social mobility may have
      been health-related, it concerns very rare and small groups; therefore health
      inequalities among the currently employed cannot be explained by
      intergenerational health-related social mobility.

PMID- 9232719
TI  - Social support and the smoking behaviour of parents with preschool children.
AB  - In a study of the relationship between social support and smoking behaviour, 1046
      parents coming with their children for well-child control at health centres in
      Oslo, Norway, completed a questionnaire. The prevalence of daily smoking
      increased with decreasing social support. However, this association did not
      remain significant when adjusting for demographic and household characteristics.
      Among smoking parents, indoor smoking at home was related to medium (OR = 1.97;
      CI: 1.01-3.81) and low social support (OR = 2.35; CI: 1.19-4.63) when adjusting
      for demographic and household characteristics. Smoking parents smoked more
      cigarettes per day when they had low social support. However, this association
      was only seen in parents with several children. In this group, smoking 10
      cigarettes per day or more was strongly related to medium (OR = 5.05; CI: 1.66
      15.35) and low social support (OR = 7.81; CI: 2.44-25.01).

PMID- 9232720
TI  - Relationships between health behavior, knowledge, and beliefs among Swedish blue
      collar workers.
AB  - The main objective of this study was to assess the health behavior, risk
      awareness and beliefs concerning the importance of positive health practices
      among blue-collar workers, and to examine the relationships between behavior,
      knowledge and beliefs. Data were gathered from 1359 workers aged 18-65 years
      using a postal questionnaire to 2493 randomly selected members of two labor
      unions. A high prevalence of negative health practices was noted among the
      respondents. While no relationship was found between health behaviors and
      awareness of risks associated with such behaviors, there was a relationship
      between positive health practices and strong beliefs about the importance of
      those practices. Awareness of the influence of a positive behavior on disease
      risk was associated with a stronger belief concerning the importance of that
      behavior. Women were characterized by having more positive health behavior, a
      higher level of risk awareness and stronger beliefs concerning the importance of
      positive health practices. It was concluded that while relationships were found
      between behavior and beliefs, and between beliefs and risk awareness, further
      research to establish the direction of the relationships is warranted.

PMID- 9232721
TI  - HIV/AIDS--information and knowledge: a comparative study of Kenyan and Swedish
      teenagers.
AB  - Knowledge of hiv/aids, exposure to hiv/aids information and appreciation of given
      information was studied, by a questionnaire, among 326 Kenyan and 146 Swedish
      teenage school students in 1994. The aim of the study was to examine differences
      and similarities in knowledge in the two populations and to examine which sources
      of information about hiv and aids the respondents had been exposed to and which
      were most appreciated. The overall knowledge about hiv/aids was high but in
      specific items the knowledge and awareness of different risk behaviours for
      contracting hiv/aids differed for the Kenyan and Swedish teenagers. The
      dissemination of hard factual information about hiv/aids has thus been successful
      in reaching out although not in stopping the spread of hiv/aids. This calls for
      new strategies in disease prevention and health promotion. Those strategies
      should focus much more on lifestyle changes. The health care system, the school
      and the existing strong civil and voluntary information structures have an
      important role to play in that work.

PMID- 9232723
TI  - Determinants of willingness to pay taxes for a community-based prevention
      programme.
AB  - Prevention can reduce the risk of disease, but has other consequences as well.
      Willingness-to-pay (WTP) is one method to analyse these multi-dimensional
      consequences, if the stated WTP is assumed to be a function of all the expected
      positive and negative effects perceived. An interview study of a community-based
      cardiovascular disease prevention programme in northern Sweden shows that
      expectations regarding reduced mortality in the community and future savings in
      public health care spending increase the perceived value of the programme. Among
      personal benefits, decreased disease risk was not positively associated with WTP,
      while a low level of anxiety was.

PMID- 9232722
TI  - The role of dairy products and non alcoholic beverages in bone fractures among
      schoolage children.
AB  - In order to assess consumption of the calcium rich dairy products, intake of non
      alcoholic beverages and physical activity as risk factors for bone fractures
      among schoolage children, a case control study was undertaken in Athens, Greece.
      During 1995 one hundred children 7 to 14 years old (74 boys and 26 girls) with
      single uncomplicated fractures of the upper and lower extremities and no evidence
      of coexisting metabolic condition affecting bone fragility were compared with 100
      age- and gender-matched controls. The analysis was undertaken by modeling the
      data through conditional logistic regression. Several indicators point to an
      increased risk of fractures among physically active children, although none of
      the individual variables was statistically significant. Somatometric factors were
      not related to fractures, although children with more advanced stage of
      development at Tanner's scale were apparently at increased risk. Intake of dairy
      products and of carbonated non cola beverages was not related to the occurrence
      of fractures. By contrast, intake of non carbonated beverages, mainly fruit
      juices, and of cola beverages were significantly associated with elevated risks
      of fractures [for an increase of one-half can per day, the odds ratios and
      associated 95% confidence intervals were 1.6 (1.2 to 2.3) and 1.7 (1.2 to 2.6)
      respectively]. In the absence of other common elements between cola and non
      carbonated beverages the positive associations of these beverages, with bone
      fractures probably reflect the increased rehydration needs of active children who
      are also at high risk for injuries.

PMID- 9232724
TI  - Deinstitutionalization of the elderly in Finland, 1981-91.
AB  - The success of Finnish deinstitutionalization policy among the elderly in 1981
      1991 was evaluated in terms of institutionalization rates and case-mix. Censuses
      of institutionalized people in all public and private residential homes and
      health centre hospitals (or nursing homes) were performed in 1981, 1986 and 1991.
      Data on demographic factors, diagnoses and dependency level were gathered.
      Censuses from the closest years of psychiatric patients were also used to obtain
      a comprehensive view of institutionalization. The eligibility criteria for the
      study were (1) age 65 years or more (2) currently in long-term care. In both men
      and women the overall relative reduction was 33%, and largest in psychiatric
      care, at over 67%. In residential home care the relative reduction was about 40%.
      In health centre hospitals a slight increase was seen, about 10%. Length of stay
      shortened in residential homes but increased in health centre wards. Dependency
      level increased among the elderly people in long-term institutional care during
      ten years. In conclusion, the deinstitutionalization rate was substantial among
      the elderly in Finland. However, because of rapid demographic change the absolute
      number of elderly in long-term care remained almost constant. The case-mix has
      become more demanding and the proportion of elderly in constant need of extensive
      help has risen.

PMID- 9232725
TI  - Transmission of Helicobacter pylori.
AB  - The epidemiology of Helicobacter pylori has been the attention of a great deal of
      study. The age and geographical distribution of infection is rapidly changing
      with improvements in living conditions, particularly in the childhood period.
      More than one mode and route of transmission is possible varying with local
      custom and practices. Infection may be acquired from environmental sources in
      certain parts of the developing world, but in most circumstances it is probably
      acquired interpersonally. Interpersonal transmission may be by either fecal-oral
      or oral-oral routes, depending on circumstances, but the former is likely to be
      the most important. The life-long chronic active gastritis associated with H
      pylori may have other consequences for health, such as growth in childhood and
      coronary heart disease.

PMID- 9232726
TI  - The expanding genus of Helicobacter: pathogenic and zoonotic potential.
AB  - The microbial flora of stomachs of humans and animals have been the focus of
      considerable research since the discovery that Helicobacter pylori in humans
      caused a variety of gastric diseases. Other Helicobacter species have now been
      isolated from the stomachs of various mammals, including dogs, cats, ferrets,
      pigs, monkeys, and cheetahs, all of which are associated with various degrees of
      gastritis in their hosts. Helicobacter species have also been isolated from the
      intestinal tracts of humans, animals, and birds. Helicobacter species have not
      only been isolated from intestines of mice but have, in addition, been isolated
      from diseased livers of inbred and outbred mice, and one of these, H hepaticus is
      linked to liver tumors. H canis and H pullorum isolated from dogs and chickens,
      respectively, have also been cultured from feces of diarrheic humans. H
      fennelliae and H cinaedi are two additional helicobacters primarily associated
      with lower bowel disease in immunocompromised humans. To date, there are at least
      13 formally named species of the new genus, Helicobacter, the majority being
      proven or suspected gastrointestinal or hepatic pathogens. Several of these
      helicobacters have zoonotic potential as well. It is predicted that additional
      Helicobacter species will be identified, and they, too, may be important
      pathogens in humans and animals.

PMID- 9232727
TI  - The role of Helicobacter pylori in the pathophysiology of duodenal ulcer disease
      and gastric cancer.
AB  - Helicobacter pylori infection is now recognized to be an important acquired
      factor in the pathogenesis of duodenal ulcer disease. There is also an
      association between H pylori and the subsequent development of gastric cancer.
      The mechanism of the association between the infection and those disorders is
      incompletely understood but there is increasing evidence that H pylori-induced
      disturbances of gastric function play a pivotal role. In this article we review
      the role of H pylori infection in the pathophysiology of these important upper
      gastrointestinal diseases.

PMID- 9232728
TI  - Pharmacological therapy of Helicobacter pylori infection.
AB  - Helicobacter pylori has been associated with several diseases including peptic
      ulcer disease and gastric cancer. Eradication of H pylori not only results in
      ulcer healing, but reduces recurrences essentially curing peptic ulcer disease.
      Eradicating H pylori can be difficult. There are several reasons for
      antimicrobial failure, and the resistance rates for several antibiotics are
      increasing. The most common drugs used to treat this infection include
      amoxicillin, clarithromycin, tetracycline, bismuth, and omeprazole and
      lansoprazole. Dual therapy using a proton pump inhibitor and a single antibiotic
      gives a suboptimal eradication rate. Triple therapy using at least two
      antibiotics and either bismuth or a proton pump inhibitor gives satisfactory
      eradication rates of 90%. However, these regimens are complicated and have
      significant side effects and compliance problems. The ideal regimen has yet to be
      developed. In the future, we will prevent infection with immunization. Several
      vaccines are being developed.

PMID- 9232729
TI  - Staying single in the 1990s: single-handed practitioners in the new National
      Health Service.
AB  - The U.K. health care system is organised around independent medical practitioners
      who work in community settings and act as gatekeepers for acute health
      interventions. Recent developments in U.K. health policy have revolutionised the
      environment within which all general medical practitioners (GPs) operate. The
      last five years in the U.K. have seen the most fundamental health service reforms
      since the inception of the National Health Service (NHS) in 1946: namely, the
      development of the internal market, an increasing emphasis on primary health
      care, and changes to the GP Contract in 1990. Single-handed GPs (practitioners
      not in partnership with other GPs) traditionally work in the most deprived areas
      with the greatest health and social problems. The current restructuring and the
      subsequent organisational and policy initiatives present particular problems for
      single-handed practitioners. How single-handed practitioners respond to the
      reforms raises particularly important debates that are significant both for
      themselves and for the populations they serve. Drawing upon a range of sources,
      this paper discusses three central issues that emerge. First, how do single
      handed practices relate to the more managerial role envisaged for authorities
      responsible for supporting primary health care? Second, given the development of
      the internal market, how do single-handed practices fare in influencing local
      policy and priority setting? Third, to what extent can single-handed
      practitioners take advantage of the opportunities to hold their own budgets?
      Overall, in the context of recent U.K. health care reforms, what is the future
      for "staying single in the 1990s"?

PMID- 9232731
TI  - From lineage to conjugality: the social context of fertility decisions among the
      Pare of northern Tanzania.
AB  - This paper is a case study of the linkages between selected characteristics of
      the social organization in a particular ethnic group and reproductive values and
      behavior. Specifically, it examines factors that might be responsible for the
      acceptance of contraception and an expressed desire for a relatively small number
      of children among the Pare of Northern Tanzania. It is hypothesized that with the
      increasing shift towards wage labor and diminishing dependence on land and
      lineage relations, there is a growing reliance on the conjugal bond and the
      development of a partnership marriage in which husbands and wives perceive their
      interests as mutual. This facilitates communication, particularly about family
      planning. Research methodology consisted of a two-pronged approach and combined
      an intensive ethnographic study of the households in the Ugwengo District of the
      Pare mountains with individual surveys administered to a sample of 512 women and
      in-depth interviews conducted with 20 women regarding the value of children and
      contraceptive and birth histories.

PMID- 9232730
TI  - Health sector reform: lessons from China.
AB  - As a result of China's transition to a socialist market economy, its rural health
      services have undergone many of the changes commonly associated with health
      sector reform. These have included a decreased reliance on state funding,
      decentralisation of public health services, increased autonomy of health
      facilities, increased freedom of movement of health workers, and decreased
      political control. These changes have been associated with growing inequality in
      access to health services, increases in the cost of medical care, and the
      deterioration of preventive programmes in some poor areas. This paper argues that
      the government's strategy for addressing these problems has overemphasised the
      identification of new sources of revenue and has paid inadequate attention to
      factors that influence provider behaviour. The strategy also does not address
      contextual issues such as public sector employment practices and systems of local
      government finance. Other countries can learn from China's experience by taking a
      systematic approach to the formulation and implementation of strategies for
      health sector reform.

PMID- 9232732
TI  - Consumerism, reflexivity and the medical encounter.
AB  - Much emphasis has been placed recently in sociological, policy and popular
      discourses on changes in lay people's attitudes towards the medical profession
      that have been labelled by some as a move towards the embracing of "consumerism".
      Notions of consumerism tend to assume that lay people act as "rational" actors in
      the context of the medical encounter. They align with broader sociological
      concepts of the "reflexive self" as a product of late modernity; that is, the
      self who acts in a calculated manner to engage in self-improvement and who is
      sceptical about expert knowledges. To explore the ways that people think and feel
      about medicine and the medical profession, this article draws on findings from a
      study involving in-depth interviews with 60 lay people from a wide range of
      backgrounds living in Sydney. These data suggest that, in their interactions with
      doctors and other health care workers, lay people may pursue both the ideal-type
      "consumerist" and the "passive patient" subject position simultaneously or
      variously, depending on the context. The article concludes that late modernist
      notions of reflexivity as applied to issues of consumerism fail to recognize the
      complexity and changeable nature of the desires, emotions and needs that
      characterize the patient-doctor relationship.

PMID- 9232734
TI  - Socioeconomic inequality and psychopathology: are socioeconomic status and social
      class interchangeable?
AB  - Two different ways of conceptualizing and measuring socioeconomic inequality
      (SEI) are described and contrasted: the commonly used socioeconomic status (SES)
      measures and a neo-Marxist measure of social class. It is argued that SES and
      social class stem from two different theoretical orientations towards
      socioeconomic inequality and that they focus on different aspects of inequality.
      These differences have implications for the role of SEI in relation to
      psychopathology. Using data from a large scale epidemiological survey that was
      conducted in Israel, it is shown that SES and social class measures are
      empirically distinct and that they explain different parts of the variance of
      psychopathology. It is concluded that since social class is theoretically as well
      as empirically distinct from SES, it has potential for contributing to our
      understanding of psychopathological phenomenon.

PMID- 9232733
TI  - Age-specific education and income gradients in morbidity and mortality in a
      Canadian province.
AB  - While important age-related trends in the use of health care services over the
      past two decades in Canada have been well described, a comprehensive description
      of socioeconomic gradients in morbidity and mortality across age cohorts for a
      representative population has not been accomplished to date in Canada. The
      objective of this study was to describe age-specific socioeconomic differentials
      in mortality and morbidity for a representative sample of a single Canadian
      province. The study sample was formed from the linkage of individual respondent
      records in the 1986 census to vital statistics records and comprehensive records
      of health care utilization for a 5% sample of residents of the province of
      Manitoba. Using two measures of socioeconomic status derived from census
      responses, attained education and household income, individuals were stratified
      into age-specific quartile ranks. Based on diagnostic information contained on
      health care utilization records, the proportion of the sample in treatment during
      a 12-month observation period was calculated for 15 broadly defined categories of
      morbidity and tested for differences across socioeconomic quartiles. Mortality
      was inversely associated with both income and education quartile rank. In the
      analysis of morbidity, no association between socioeconomic status and treatment
      prevalence was observed in the majority, no association between socioeconomic
      status and treatment prevalence was observed in the majority of the 122 age- and
      disorder-specific strata tested. Of the observed associations, however, negative
      relationships were dominant, indicating a higher treatment prevalence among
      individuals of lower attained education or lower household income. Across the age
      course, negative relationships were most frequently present among young and
      middle aged adults, those aged 30-64, and were more consistently found for income
      than for education. The general findings of this study of a representative
      Canadian population support observations from other developed country settings
      that socioeconomic differences in relative rates of mortality and morbidity over
      the life course are greatest in the adult years.

PMID- 9232735
TI  - Prediction of psychological adjustment to multiple sclerosis.
AB  - This study examined the utility of self-efficacy as a predictor of social
      activity and mood control in multiple sclerosis (MS). Seventy-one subjects with
      MS were recruited from people attending an MS centre or from a mailing list and
      were examined on two occasions that were two months apart. Clinic patients were
      more disabled than patients who completed assessments by post, but they were of
      higher socioeconomic status and were less dysphoric. We attempted to predict self
      reported performance of mood control and social activity at two months, from self
      efficacy or performance on these tasks at pretest. Demographic variables,
      disorder status, disability, self-esteem and depression were also allowed to
      compete for entry into multiple regressions. Substantial stability in mood,
      performance and disability was observed over the two months. In both mood control
      and social activity, past performance was the strongest predictor of later
      performance, but self-efficacy also contributed significantly to the prediction.
      The disability level entered a prediction of social activity, but no other
      variables predicted either type of performance. A secondary analysis predicting
      self-esteem at two months also included self-efficacy for social activity,
      illustrating the contribution of perceived capability to later assessments of
      self-worth. The study provided support for self-efficacy as a predictor of later
      behavioural outcomes and self-esteem in multiple sclerosis.

PMID- 9232736
TI  - Anxiety and patient participation in clinical decision-making: the case of
      patients with ureteral calculi.
AB  - Ninety-six patients with a ureteral calculus participated in a study whose
      purpose was to identify those subjects who would benefit from participation in
      clinical decision-making. Forty-two of the subjects (the experimental group) were
      given information about two alternative treatments, Extra Corporeal Shock Wave
      Lithotripsy (ESWL) and ureteroscopy, and were asked to choose which therapy they
      preferred. Fifty-four subjects (the control group) were not given information,
      not allowed to choose, and were treated according to the physician's decision.
      Subjects' level of anxiety was compared within each group on three occasions:
      before meeting with the physician, immediately afterwards and upon
      hospitalization for treatment of the stone. Patients perception of receipt of
      information and participation in clinical decision-making, coping style,
      educational level, and knowledge about treatment alternatives were also measured.
      A statistically significant decrease in anxiety after meeting with the urologist
      was found among patients who were not asked to participate in the decision-making
      process and among patients who perceived that they had received information. A
      decrease in anxiety after meeting with the physician was also found among
      patients who, according to their own perception, did not participate in decision
      making. Patients' educational level and coping style were related to their
      anxiety. A decline in anxiety was found among those with a lower educational
      level who perceived that they had received information and among higher educated
      patients who perceived that they participated in clinical decision-making.
      Anxiety also declined among patients with a passive coping style who perceived
      that they had received information or had participated in the decision-making
      process. The results emphasize the need to tailor the therapeutic approach to
      patient characteristics.

PMID- 9232737
TI  - Back pain claim rates and the business cycle.
AB  - The causes of reported occupational back pain are controversial. Many observers
      appear to believe that job insecurity increases back pain compensation claims
      during recessions. The purpose of this study was to formally examine the impact
      of macro-economic forces-the business cycle-on the incidence of lost-time back
      pain claim rates in order to elicit clues to both its aetiology and reporting
      patterns. For Ontario between 1975 and 1993, age- and sex-adjusted lost-time back
      pain claim rates, stratified by industry sector (construction, manufacturing and
      trade), were regressed on the unemployment rate of the industry sector using time
      series methods. As a comparison group, the association between "acute" claim
      (fractures, lacerations, etc.) and the business cycle was also tested. Both back
      pain claim rates and acute claim rates increased during boom periods and
      decreased during recessionary periods. Time series analyses confirmed that these
      associations were statistically significant. The elasticities between claim rates
      and the unemployment rate were similar for back pain claims and acute claims. In
      addition, these associations were consistent in direction across all three
      industrial sectors tested. These results rebut the view that back pain claims
      increase during recessionary times.

PMID- 9232738
TI  - The modern mental health system in Nepal: organizational persistence in the
      absence of legitimating myths.
AB  - This paper advances an organizational explanation for the slow pace of
      modernization of mental health care systems in developing societies. In
      complement to cultural and political economic explanations of this condition, we
      suggest that the value of establishing modern systems in developing societies
      lies in the legitimation such structures provide for indigenous modernizing
      efforts vis-a-vis both indigenous and external audiences. The system need not
      meet actual levels of service demand. Its importance is in its symbolic value as
      an indicator of modernity. The result is a system in "permanent failure".
      Implications for institutional theory and the growth of modern mental health
      systems in developing societies are discussed.

PMID- 9232739
TI  - An unruly melange? Coordinating external resources to the health sector: a
      review.
AB  - The past two decades have witnessed an upsurge in the number of external agencies
      involved in the health sectors of developing countries. Concomitantly, there has
      been an increase in the volume of resources transferred through multilateral,
      bilateral and non-governmental organizations to these health systems.
      Notwithstanding the beneficial impact of increased resources, recipients and
      donors are increasingly concerned about the effects of this trend. This is
      particularly pertinent where the effort lacks adequate coordination. Recipients
      despair of an unruly melange of external ideas and initiatives, that too often
      results in project proliferation and duplication, unrealistic demands, and
      ultimately a loss of control over the health development process. Donors on the
      contrary, are concerned about aid efficiency and effectiveness, two areas it is
      assumed will gain from increased attention to coordination. Both recipients and
      donors are looking for ways of better managing the aid relationship. Although
      there has been considerable experience with coordination strategies, most writing
      has considered external assistance in general, rather than the health sector in
      particular. The literature is striking in its bias towards the needs and
      perspectives of the donor community. There has been little analysis of the manner
      in which recipient ministries of health manage donors and the influx of
      resources. This review begins to fill this gap. Its focus is country-level, where
      most direct gains from coordination are to be reaped. The paper begins with an
      enumeration of the many and diverse trends which have raised the salience of aid
      coordination. A definition of coordination, a term used ambiguously in the
      existing literature, is then developed and the principles of aid coordination
      outlined. Finally, attention is directed to the initiatives of recipients and
      donors to improve the coordination of health sector aid.

PMID- 9232740
TI  - Disadvantage and male cancer incidence and mortality in New South Wales 1985
      1993.
AB  - Male premature mortality variations from cancers by socioeconomic status and
      marital status were analysed for the period 1986-1989 and 1990-1993 for New South
      Wales. Cancer incidence and mortality were also surveyed by statistical local
      areas within metropolitan Sydney between 1985-1991 and correlation and regression
      analyses were undertaken with socioeconomic indicators and the modified Jarman 8
      disadvantage indicator. Martial status variations were found with most major
      cancers, with not currently married men being more at risk. Cancers of the
      oesophagus, oral cavity, pancreas, bladder, kidney, liver and trachea, bronchus
      and lung were more associated with manual occupations and the disadvantage
      indicator, while cancer of the colon and melanoma were more associated spatially
      and occupationally with higher socioeconomic status. An unexpected finding with
      mortality was an occupational status bipolarity with several cancers, notably
      with managerial and manual workers. There are implications for the more precise
      targeting of populations at risk.

PMID- 9232741
TI  - Awareness of dying: prevalence, causes and consequences.
AB  - Analysis of a subset of data from a survey of 3696 relatives, friends and others
      who knew a sample of people dying in 1990 who lived in 20 areas of the United
      Kingdom (the Regional Study of Care for the Dying) is reported. Using the
      typology of awareness contexts developed by Glaser and Strauss [(1965) Awareness
      of Dying, Aldine, Chicago], the prevalence of different awareness contexts is
      described and compared with an earlier survey done in 1969. Open awareness of
      dying, where both the dying person and the respondent knew that the person was
      dying, is the most prevalent awareness context. This is particularly so in cancer
      and represents a change since 1969 when closed awareness (where the respondent
      knows, but the dying person does not) was more common. The characteristics of
      those dying in open and closed awareness contexts are then compared, suggesting
      that having cancer, not being mentally confused, having a respondent who knew for
      some time that the person was dying, and being of higher social class are
      independently predictive of full open awareness, a condition marked both by
      knowledge of dying, and a value commitment towards openness. Compared with people
      in closed awareness, people dying in full awareness are more able to plan their
      dying careers, so that they and their respondents are more satisfied with the
      degree of choice over the place of death, they are less likely to die alone, and
      are more likely to die in their own homes. Additionally, these individuals are
      more likely to have spoken of their wishes for euthanasia, another indicator of
      their desire to control the manner and timing of death. If dying from cancer,
      people in full open awareness are more likely to have received hospice care. It
      is suggested that underlying these patterns, and in contrast with some other
      cultures where awareness of dying is seen as less desirable, people dying in
      Anglophone countries are particularly concerned to maintain control over projects
      of self-identity. Their approach to death is a reflection of this individualism.

PMID- 9232742
TI  - Ethnicity, equity and the use of health services in the British NHS.
AB  - This paper addresses the extent to which equity of treatment is received by
      people of different ethnic groups from the British National Health Service. Using
      data from the General Household Surveys of 1984-91 it examines the use of general
      practitioner, outpatient services using three different methods to adjust for
      need and for other possible confounding variables. The results do not suggest
      there is any gross pattern of inequity between ethnic groups, except perhaps with
      respect to the Chinese population which displays consistently low levels of
      utilisation. However, while use of GP services by minority ethnic groups is in
      general as high or higher than the white population, use of outpatient service is
      low. Some of the results also suggest that there may be important ethnic
      differences underlying the broader finding of equity. For example, females of
      Pakistani origin report low levels of GP use. More generally, excess use of GP
      services among several minority ethnic groups appears to be associated with need,
      while people from most minority ethnic groups who do not report illness display
      especially low use of outpatient services relative to the corresponding group in
      the white population. The paper examines the implications of these findings.

PMID- 9232743
TI  - Problem-based learning in medicine: new curriculum, old stereotypes.

PMID- 9232744
TI  - Treatment of patients with spinal cord lesions in Germany 1996--state of the art.
AB  - Modern treatment of sufferers from spinal cord lesions according to the
      guidelines elaborated by Sir Ludwig Guttmann in the UK started in specialised
      centres in Germany some 45 years ago. At the present time the incidence is 18
      cases/l million/year traumatic and non traumatic. Exact figures are available
      since 20 years ago. Twenty-one appropriate centres with altogether 1071 beds are
      able to admit almost all traumatic cases and 30% of non traumatic cases for
      'comprehensive treatment'. That includes cervical lesions above C4 as well as
      patients with polytrauma, intensive care, spinal column surgery, sophisticated
      urological diagnostic and treatment, physio- and occupational therapy,
      psychological and social assistance. To fulfill all tasks arising from lifetime
      care and readmissions there is a need of another 800 beds in specialised centres
      not dealing with recent cases. The original principle to offer first treatment
      and life-time follow up 'under one roof' is to be given up as conservative
      treatment of the broken spine has been continually replaced by spinal surgery
      done in non specialised primary admitting regional hospitals. Priority is given
      to the aim to offer similar opportunities to everyone by providing 800 additional
      beds in new specialised centres.

PMID- 9232745
TI  - Trends in the treatment of patients with spinal cord lesions seen within a period
      of 20 years in German centers.
AB  - Twenty-one special centers are running treatment of spinal cord injuries in
      Germany. Their heads represent a study group to coordinate methods and to
      investigate results collecting data since 1976. So we have experiences for about
      20 years. 1500 recent cases are treated per annum. Seventy-five percent got their
      lesion by trauma. Beside these there is only a little capacity to treat patients
      with non-traumatic or congenital lesions (25%). Sixty-two percent are para-, 38%
      are tetraplegic, 28% female, 2% are children. Within 22,212 recent cases 35% got
      their injury by traffic, 14% at work. Sports and diving caused 4%, suicide 5% and
      killing attempts 1%. Though numbers since 1976 are decreasing, traffic and work
      are main reasons causing spinal injuries. Readmission reasons are mainly
      disorders of soft tissues (23%) and the urinary tract (21%). Out-patients are
      checked in 67% of all cases. All investigation data represent very stable trends
      within the last 20 years. Altogether the special centers carried out treatment
      and consultation in about 22,000 recent cases, 45,000 readmissions and 80,000 out
      patients.

PMID- 9232747
TI  - Strategy for the treatment of patients with spinal neoplasms.
AB  - Progress in oncological therapy within the last decade has enhanced the survival
      time of patients suffering from tumorous osteolyses of the spine. While the
      necessity of surgical intervention is often settled by acute clinical symptoms,
      the extent of surgery is certainly co-determined by the patient's expectations
      and the time of survival to be expected. We therefore developed a specific tumor
      algorithm for operations on the spine with special emphasis on prognosis and the
      attainable quality of life. The results of 154 patients with tumorous osteolyses
      of the thoracic and lumbar spine, who were treated according to our algorithm,
      underline the unequivocal advantages of initially posterior procedures.

PMID- 9232746
TI  - The surgical treatment of acute spinal paralysed patients.
AB  - Following the basic principles of Sir Ludwig Guttmann in respect of the
      comprehensive care and management of spinal cord injured patients, the German SCI
      centers try to admit those freshly injured preferably on the first day of onset,
      providing spinal surgery and intensive care. In our series of recent
      comprehensive spinal paralysed patients admitted from Jan 1st 1993 to Dec 31st
      1995 178 patients requested operative decompression and stabilization out of a
      total of 255 patients. 51.4% of the patients had been operated within the first
      24 h, but 10.5% later than 2 weeks. A high incidence of reoperations (45.2%) must
      be noted in cases operated prior to the admittance to the SCI center due to
      failures of instrumentation or lack of anterior reconstruction. Nineteen patients
      with various spinal tumors underwent surgical treatment, and seven patients with
      spondylitis and severe neurological deficit. Only 64.4% of the 1st day admissions
      came in time for administration of high dose methylprednisolone according to the
      NASCIS II study. The additional pelvic and long bone fractures were operated on
      following the principles of the Swiss AO, thus achieving immediate mobilization
      as was also possible after surgical spine stabilization. Neurological recovery
      could only be found in those with incomplete lesions in more than 50% but also
      two with neurological deterioration had to be accepted in the paraplegic cohort.
      Eight who were tetraplegic and 14 with paraplegia died within the first 3 months,
      but nine with paraplegia had a tumor or spondylitis.

PMID- 9232748
TI  - Applications of the pedicled vastus lateralis flap for patients with complicated
      pressure sores.
AB  - The vastus lateralis muscle- or musculocutaneous flap is a well established tool
      in the surgery of pressure sores of the pelvic region. Its size, its constant
      large axial vascular pedicle originating from the lateral circumflex femoral
      artery, and its ability to carry quite a large skin island from the distal
      lateral region of the upper thigh makes this flap a very versatile one in the
      management of difficult situations. The vastus lateralis flap allows the
      simultaneous closure of defects in the trochanteric and sacral region, a
      technique which has not been described previously. A pedicled vastus lateralis
      flap may be the only remaining local salvage procedure for defects due to
      obstruction of internal and external iliac arteries and aortobifemoral bypass
      surgery. This is another application which has not yet been described in the
      medical literature. The outcome of a series of 38 vastus lateralis flaps and the
      complications are shown. The follow-up period ranged from 3 months to 4 years.
      One flap was lost. More complications were seen at the donor site than at the
      reconstructed defect. In patients who may be able to walk or stand at a later
      date, potential impairment of these functions has to be considered. In our
      opinion, the vastus lateralis flap is an excellent tool for managing large tissue
      defects in difficult situations.

PMID- 9232749
TI  - Resection of heterotopic ossification of the hip in spinal cord injured patients.
AB  - Twenty nine spinal cord injury patients were treated by resection of heterotopic
      ossification in 41 hips. The average follow-up period after surgery was 4.2
      years. The mean time to surgery after injury was 82.1 months. The indications for
      surgery were seating problems, loss of function, pressure sores and pain. The
      average preoperative motion in flexion and extension was 21.95 degrees, the
      average intraoperative motion was 94.51 degrees. The average motion at follow-up
      evaluation was 82.68 degrees. Clinical relevant recurrence occurred in three
      patients. Complications excluding recurrence occurred in 10 hips, including deep
      and superficial wound infections, fracture, aneurysm and pressure ulcer. The
      operation was followed by a specific regime of physiotherapy and radiation
      therapy.

PMID- 9232750
TI  - Chronic pain/dysaesthesiae in spinal cord injury patients: results of a
      multicentre study.
AB  - The aim of the multicentre study entitled 'Description and Documentation of
      Painful States in Spinal Cord Injury Patients', in addition to the description
      and documentation of chronic pain and stressful dysaesthesiae in SCI patients,
      was the search for correlations between these symptoms and medical and
      psychosocial variables. To this end, the sample was selected to be as
      representative as possible. All patients referred for in-patient or out-patient
      treatment at the centres taking part were enrolled in the study in order of
      presentation, providing they gave consent and met the inclusion criteria.
      Psychosocial, medical and demographic data were elicited by a standardized
      battery of questions and a standardized physical examination, as were any chronic
      pain/dysaesthesiae (P/D) present in any localization. Among 901 patients, 34% had
      no chronic pain or dysaesthesiae, 50% had pain only, 11% had painful
      dysaesthesiae and 5%, non-painful but chronic and distressing dysaesthesiae. The
      intensity of P/D was noted as seven or more on a 10 cm visual analogue scale by
      61% of the patients affected and was experienced as rather or very distressing in
      75% of cases. Most (86%) P/D were located below the spinal lesion or in the
      transition zone. There were significant correlations between the presence of P/D
      and age on questioning and at onset of the paraplegia/tetraplegia, problems with
      rectal paralysis, expectations of life as a paraplegic/tetraplegic, and
      subjective assessment of changes in working life. Highly significant correlations
      were found with subjective distress resulting of paraplegia/tetraplegia as such,
      depressed mood and psychosomatic disturbances of wellbeing. Overall, among the
      selected variables of our study, we found that correlations between P/D and
      psychosocial variables were more frequent and closer than those between P/D and
      medical variables.

PMID- 9232751
TI  - Bladder autoaugmentation in adult patients with neurogenic voiding dysfunction.
AB  - Bladder autoaugmentation offers an alternative to enterocystoplasties for
      patients with low capacity high pressure bladders caused by non-malignant
      pathology. In particular for patients with neuropathic hyperreflexive bladders,
      refractory to less invasive therapy, bladder autoaugmentation will attain
      comparable results with less impact on life quality compared to other bladder
      augmentation procedures. The procedure does not preclude later enterocystoplasty
      or deafferentations. Over the last 7 years, 50 patients were treated by this
      method, some of them for other than neurogenic voiding dysfunction. Substantial
      increase of bladder capacity and compliance resulted, at the cost of increased
      residual urine and the need for intermittent catheterisation in most patients.
      Some patients are able to perform complete voiding at will. The time lapse
      between surgery and functional rehabilitation of the bladder (substantial
      increase of capacity and detrusor compliance) cannot be predicted yet. In most
      patients this amelioration was observed 1-6 months after surgery, but in some the
      effect was equivocal for a year or longer. Low-dose anticholinergics appear to
      speed up the therapeutic effect. One patient had enterocystoplasty and one
      deafferentation later, one had rupture of the bladder, probably from the use of
      an artificial sphincter, and two are rated as failures because of psychogenic
      bladder-centred problems. Bladder autoaugmentation is a favourable treatment for
      patients who are motivated to wait possibly longer for functional changes to
      occur and are willing to perform intermittent catheterisation afterwards.

PMID- 9232752
TI  - Conservative and surgical semen retrieval in patients with spinal cord injury.
AB  - Assisted semen retrieval was applied in 219 men with spinal cord injury (212
      supranuclear, seven infranuclear lesions). Vibrostimulation in supranuclear
      lesions was successful in 133, and in five more after physostigmine injection.
      Electroejaculation was successful in all seven infranuclear lesions and in four
      supranuclear patients failing with vibrostimulation. Eight more supranuclear
      patients responded to electroejaculation and physostigmine. Surgical retrieval
      was applied in 27 patients. Nine Wagenknecht spermatoceles showed only one
      success, from all 18 implanted Brindley reservoirs semen could be collected.
      Three patients, in whom no pregnancy could be induced after Brindley reservoir
      implantation, had testicular sperm aspirated. In 109 patients who wanted to have
      offspring, 73 pregnancies could be induced in 46 couples, leading to 54 births
      (four twins), 16 abortions and three pregnancies. Conservative semen retrieval
      was possible in 82 of these men (63 pregnancies in 37 couples) and surgical
      methods were used in 27 (10 pregnancies in nine couples).

PMID- 9232753
TI  - Regeneration of lesioned corticospinal tract fibers in the adult rat spinal cord
      under experimental conditions.
AB  - The absence of fiber regrowth in the injured spinal cord and brain is influenced
      by several different factors and mechanisms. Among these are factors which
      inhibit neurite growth which are found on the surface of oligodendrocytes and
      central myelin. Their neutralization by a specific antibody allowed regeneration
      of transected corticospinal tract fibers in the adult rat spinal cord. Using a
      recently introduced novel neuroanatomical tracer, biotin-dextran-amine, we
      demonstrate the extensive regenerative sprouting of lesioned corticospinal fibers
      in the lesioned adult spinal cord. In the presence of the antibody against the
      myelin-associated neurite growth inhibitors, some of these fibers grew over
      remaining tissue bridges into the caudal spinal cord. They branched extensively
      in the lumbar spinal cord segments. These branches were decorated with synapse
      like boutons. This neuroanatomical configuration probably contributes importantly
      to the functional recovery observed earlier in these antibody-treated animals.

PMID- 9232754
TI  - Axotomy-induced alterations in the red nucleus revealed by monoclonal antibody,
      Py, following a low thoracic spinal cord lesion in the adult rat.
AB  - The monoclonal antibody Py was previously developed as a tool for the
      identification of subpopulations of hippocampal neurons. Here, the differential
      distribution of Py immunoreactivity in the mid-brain is described showing that Py
      also serves as a useful marker for other populations of neurons. Medium to strong
      immunoreactivity was observed in the cell body and dendrites of neurons of the
      oculomotor nucleus, superior colliculus and substantia gelatinosa reticulata.
      However, particularly intense Py-immunoreactivity was identified in the
      magnocellular neurons in the caudal pole of the red nucleus. Unilateral
      transection of the rubrospinal tract at Th9-10 induced a marked reduction of Py
      immunoreactivity in the ventrolateral territory of the caudal pole of the
      axotomised red nucleus. A small but statistically significant reduction of Py
      immunoreactivity was first seen at 7 days after surgery and a maximal loss of
      immunoreactivity (reduced to 66% of control levels) was observed by 21 days after
      surgery. Immunoreactivity in the axotomised red nucleus was reduced for the
      duration of the experiment but at the longer survival times studied (3 and 6
      months) a small degrees of recovery of staining was observed in small-medium
      diameter atrophic neurons. These results indicate that monoclonal antibody Py,
      may be a useful novel and sensitive tool for investigating the cell body reaction
      of particular populations of axotomised CNS neurons following spinal cord injury.

PMID- 9232755
TI  - Bayesian analysis for a single 2 x 2 table.
AB  - The simple comparison of two binomial populations is frequently of interest in
      epidemiology when the domains are large. For small domains, however, there are no
      exact methods except Fisher's exact test. A basic problem, therefore, is to
      compare two populations by assessing the difference between the proportions of
      individuals who possess a characteristic in the first and second populations.
      When there is prior information, we take the proportions to have independent
      conjugate beta distributions with known parameters, thereby facilitating a
      Bayesian analysis. We consider Bayesian inference on functions of the
      proportions, and the three most common scalar measures used in epidemiology and
      health services research, namely relative risk, odds ratio and attributable risk.
      We develop the highest density regions (both exact and approximate) for relative
      risk, odds ratio and attributable risk. In addition, we consider the Bayes factor
      for testing whether the model with a common proportion holds rather than one with
      distinct proportions. Using data from the population-based Worcester Heart Attack
      Study, we apply our methodology to study gender differences in the therapeutic
      management of patients with acute myocardial infarction (AMI) by selected
      demographic and clinical characteristics. The Bayes factor, the approximate and
      exact intervals generally suggest that there are no substantial differences in
      the pharmacologic management of males and females hospitalized with AMI.

PMID- 9232756
TI  - A non-iterative accurate asymptotic confidence interval for the difference
      between two proportions.
AB  - I propose a new confidence interval for the difference between two binomial
      probabilities that requires only the solution of a quadratic equation. The
      procedure is based one estimating the variance of the observed difference at the
      boundaries of the confidence interval, and uses least squares estimation rather
      than maximum likelihood as previously suggested. The proposed procedure is non
      iterative, agrees with the conventional test of equality of two binomial
      probabilities, and, even for fairly small sample sizes, appears to yields actual
      95 per cent confidence intervals with mean or median probabilities of coverage
      very close to 0.95. The Yates continuity correction appears to generate
      confidence intervals with the conditional probability of coverage at least equal
      to nominal levels.

PMID- 9232757
TI  - A comparison of spatial prediction techniques for an exploratory analysis of
      human cortical motor representations.
AB  - We compare the use of two-dimensional Laplacian smoothing splines and median
      polish kriging for an exploratory analysis of spatial data sets. Splines were
      developed originally for modelling a process with determinstic mean structure,
      while median polish kriging was developed for predicting a spatial random
      process. We review the fundamentals of both methods, including smoothing
      parameter selection for splines and variogram estimation and solving the kriging
      equations for median polish kriging. We demonstrate application of the methods on
      maps of muscle representations on the human motor cortex (cortical maps). After
      applying both methods to 20 cortical maps (left and right hemispheres on each of
      10 subjects), we compare the fitted surfaces on the basis of predictive ability,
      aesthetic appeal, and ease of computation.

PMID- 9232758
TI  - Using smoothing spline anova to examine the relation of risk factors to the
      incidence and progression of diabetic retinopathy.
AB  - Smoothing spline ANOVA (ANalysis Of VAriance) methods provide a flexible
      alternative to the standard parametric GLIM (generalized linear models) methods
      for analysing the relationship of predictor variables to outcomes with data from
      large epidemiologic studies. These methods allow the visualization of
      relationships not readily fit by simple GLIM models, and provide for the ability
      to visualize interactions between the variables. At the same time, they reduce to
      GLIM models if the data suggest that the added flexibility is unwarranted. Using
      this method, we investigate risk factors for incidence and progression of
      diabetic retinopathy in a group of patients with older onset diabetes from the
      Wisconsin Epidemiological Study of Diabetic Retinopathy. We carry out four
      analyses to illustrate various properties of this class of methods. Some of the
      results confirm previous findings with use of standard methods, while others
      allow the visualization of more complex relationships not evident from the
      application of parametric methods.

PMID- 9232759
TI  - Re-using data from case-control studies.
AB  - Despite its ability to maximize statistical power while keeping data collection
      costs to a minimum, case-control sampling provides a non-representative sample of
      the population. When fitting a logistic regression model to data obtained in such
      a study, using the variable stratifying the population as the response, it is
      well known that the estimate of the constant term will be biased, but those of
      the coefficients of the covariates will not. However, subsequent to the case
      control study, it is often desired to conduct a secondary analysis, using a
      variable that was previously a covariate in the main study as the response. If
      this new response is associated with the original variable used to stratify the
      population into cases and controls, a conventional logistic regression analysis
      will usually result in biased estimates of all the regression coefficients, not
      just the constant. This situation has recently been studied by Nagelkerke et al.
      who describe some situations where no bias occurs. In this paper we discuss how
      to calculate maximum likelihood estimates of all the regression coefficients, in
      the situation where the sampling rates for cases and controls are known. An
      example using data from the New Zealand Cot Death Study is presented.

PMID- 9232760
TI  - Bias in the evaluation of DNA-amplification tests for detecting Chlamydia
      trachomatis.
AB  - The purpose of this paper is to show that the sensitivity and specificity
      estimates obtained by 'discrepant analysis' are biased. Discrepant analysis is a
      widely used technique that attempts to provide estimates of sensitivity and
      specificity in the presence of an imperfect gold standard. Many researchers have
      applied this technique to estimate the sensitivity and specificity of DNA
      amplification tests for Chlamydia trachomatis such as the plasmid based ligase
      chain reaction (LCR) and polymerase chain reaction (PCR) tests. Moreover, the
      June 1993 package insert of the PCR AMPLICOR Chlamydia trachomatis test contains
      estimates of sensitivity and specificity based on 'discrepant analysis'. Even if
      one employs a perfect test to resolve the discrepant results, discrepant analysis
      estimates of test sensitivity and specificity remain biased. Thus, one should not
      adopt this technique to evaluate the performance of a diagnostic test.

PMID- 9232761
TI  - The efficiency of the sets and the cuscore techniques under biased baseline
      rates.
AB  - Statistical techniques used for surveillance of disease incidence rates are
      generally based on the assumption of known baseline rate of the disease
      monitored, whereas actually it is an estimate obtained from a large sample. As a
      result, the time interval until true or false alarm is shorter or longer than
      assumed. In this study, we evaluate the performance of the sets and of the
      cuscore techniques when the estimate of the baseline rate is biased. We evaluate
      the effect of an underestimated baseline rate with respect to frequency of false
      alarms and to that of an over estimated rate with respect to the delay until
      elicitation of a true alarm. We evaluate the effects of 5 per cent and 10 per
      cent bias in the estimated baseline rate for specified conditions associated with
      sparse data. The results show that the effect of plus or minus 5 per cent bias in
      the estimate are moderate and those of 10 per cent are substantial. In general,
      the effect of an overestimated baseline rate is greater on the sets technique
      than it is on the cuscore technique and the effect of an underestimated rate is
      greater on the cuscore technique than it is on the sets technique. However, the
      differences between the two techniques are small on both perspectives. The two
      methods differ also with respect to the expected time until true alarm when the
      specified baseline rate is unbiased. The sets technique is the more efficient in
      detecting a two-fold increased rate when the number of diagnoses expected
      annually (E(X)) is less than 1.62, and the cuscore is the more efficient
      technique when E(X) > 1.62. We use the term 'turning point' to define the regions
      in which the sets technique and the cuscore techniques are preferred. With an
      estimated baseline rate that is 5 per cent higher than the actual rate, the
      turning point falls from 1.62 to 1.45 when the rate is twice the baseline rate,
      and from 5.75 to 4.34 when the rate is triple the baseline rate.

PMID- 9232762
TI  - Tutorial in biostatistics Bayesian data monitoring in clinical trials.
AB  - Many clinical trials organizations use regular interim analyses to monitor the
      accruing results in large clinical trials. In disease areas such as cancer, where
      survival is usually a major outcome variable, ethical considerations may lead to
      a stipulated requirement for data monitoring of mortality. This monitoring has
      frequently taken the form of limiting interim analyses to be few in number, and
      specifying an extreme p-value of, for example, p < 0.001 or p < 0.01 as grounds
      for early termination of the trial. Group-sequential methods are also used.
      However, none of these approaches formally assesses the impact that the results
      of a clinical trial may have upon clinical practice. Thus a trial might be
      terminated early because of apparent treatment benefits, but might fail to
      influence sceptical clinicians to modify their future treatment policy. We
      discuss the application of Bayesian methods, including the use of uninformative,
      sceptical and enthusiastic priors, and demonstrate that the necessary
      calculations are both straightforward to perform and easy to interpret
      statistically and clinically. Methods are illustrated with interim analyses of a
      clinical trial in oesophageal cancer.

PMID- 9232763
TI  - The history of ultrasound in gynecology 1950-1980.
AB  - The pioneers of gynecological ultrasound were active from 1950 to 1960. In this
      period, compound contact scanning was developed. The disciples who followed were
      responsible for the explosive growth that had occurred by 1975. The indications
      for diagnostic ultrasound in gynecology were, first, in cystic and solid masses;
      they increased steadily to include nonpalpable pelvic masses, ascites, ovarian
      tumors, cervical lesions, early pregnancy, localization of intrauterine devices,
      cancer, pelvic inflammatory disease and many more. The techniques also evolved
      from A-mode, through two-dimensional B-mode, grey tones and special probes, to
      guided procedures. Signs of tissue anomalies and approaches to tissue
      characterization were explored. Figures were established to demonstrate the
      usefulness of diagnostic ultrasound in gynecology in numerous clinical
      conditions. The review ends with some personal recollections of the early
      workers, a discussion of the contemporary treatment of the safety of the method
      and notes on some of the first textbooks.

PMID- 9232764
TI  - Bone status after long-term anticonvulsant therapy in epileptic patients:
      evaluation using quantitative ultrasound of calcaneus and phalanges.
AB  - The bone status of 25 epileptic female patients on long-term (mean 19 y)
      anticonvulsant therapy was investigated using quantitative ultrasound of the
      calcaneus (Lunar Achilles) and phalanges (Igea DBM Sonic 1200). Comparisons were
      made with a control group of 43 normal healthy women. Radiogrammetric
      measurements of the second metacarpal bone were also made in the epileptic
      patients. While all of the ultrasonic parameters were reduced in the epileptic
      group, differences only achieved statistical significance for speed of sound
      (SOS) at the phalanges. Phalangeal SOS correlated significantly with cortical
      thickness of the second metacarpal bone (r = 0.44, p < 0.05). The data suggest
      that long-term anticonvulsant therapy is associated with significant cortical
      bone loss. Quantitative ultrasound may have a role in monitoring bone loss in
      epileptic patients and in guiding suitable preventive therapy.

PMID- 9232765
TI  - Characterization of echographic image texture by cooccurrence matrix parameters.
AB  - The goal of this study was to investigate the potentials of cooccurrence matrix
      analysis for the characterization of echographic image texture. Echographic data
      were obtained by one-dimensional simulations. Various data sets were generated
      with different number densities of the randomly distributed scatterers and with
      different levels of structural scattering strength. Cooccurrence matrix
      parameters estimated for analysis were: angular second moment, contrast,
      correlation, entropy and kappa. The cooccurrence matrix analysis was tuned by
      varying its parameters: spatial displacement of the pixel pairs, number of gray
      levels and size of the window. The parameters reached a saturation level at a
      number density of 3-5 scatterers per resolution cell (-6 dB width). Similarly,
      when increasing the displacement, a limit value was reached at 4-20 samples,
      depending on the size of the resolution cell. Using the Mahalanobis distance as a
      measure of differentiating between two textures, a systematic inverse relation
      was observed between the size of the window and the number of gray levels used in
      the estimation of the cooccurrence matrix. The optimal parameters to
      differentiate textures without structure appeared to be entropy and angular
      second moment. A window size of 90 speckle cells and 64 gray levels is needed for
      this purpose. The effective speckle size was estimated from the mean number of
      maxima of the demodulated echo signals. Resolved structure results in a
      periodicity of parameter values with displacement. The periodicity can be
      calculated by changing the displacement d. Optimal parameters for detecting
      periodicity are contrast and correlation. Analysis of the correlation between
      parameters showed that entropy vs. angular second moment and contrast vs.
      correlation are highly correlated.

PMID- 9232766
TI  - Correlation of ultrasound parameter imaging with microcirculatory patterns in
      uveal melanomas.
AB  - Previous studies demonstrated a correlation between acoustic backscatter
      parameters and survival in ocular melanoma. The histologic presence of
      microvascular networks in ocular melanoma is also associated with death from
      metastases. This study tests the hypothesis that melanomas grouped on the basis
      of these microvascular patterns are separable by ultrasound spectrum analysis. We
      scanned 40 melanomas using a 10-MHz ultrasound unit equipped for digitization of
      radio frequency data. After enucleation, tumors were sectioned in planes
      corresponding to the ultrasonographic examination and stained to demonstrate
      microcirculation. Acoustic spectral parameters were compared between 14 melanomas
      with a nevuslike microcirculation and 26 with foci of high-risk microvascular
      structures. Smaller scatterer size, lower acoustic concentration and greater
      spatial variability were found to correlate with high-risk microvascular patterns
      and areas of cystic degeneration. We suggest that nonvascular extracellular
      matrix components associated with microvessels may be responsible for the
      correlation of acoustic parameters with microvascular pattern and distribution.

PMID- 9232767
TI  - Reproducibility of shear rate and shear stress assessment by means of ultrasound
      in the common carotid artery of young human males and females.
AB  - In the present study, the reliability of an ultrasonic shear rate estimating
      system, in terms of intrasubject intrasession, intersubject intrasession and
      intersubject intersession variability coefficients for the assessment of wall
      shear rate (WSR) in the common carotid artery (CCA) was determined in eight
      presumed healthy volunteers. Measurements were performed on consecutive days (day
      1, day 2 and day 7). To investigate whether there were differences in WSR due to
      gender, dynamic WSR in the CCA was assessed in 11 presumed healthy males (mean
      age 24 y) and 11 presumed healthy females (mean age 25 y). Wall shear stress
      (WSS) was estimated from WSR and calculated whole blood viscosity. The average
      intrasubject intrasession variability was about 15% for peak WSR and about 12%
      for mean WSR. The intersubject intrasession variability for peak WSR decreased
      from 19% on day 1 to 16% on day 7 and for mean WSR from 17% on day 1 to 11% on
      day 7. The intersubject intersession variability is on the order of 5% for peak
      WSR and about 4% for mean WSR. No significant differences could be detected
      between peak and mean WSR values on day 1, day 2 and day 7, indicating good short
      and medium-term intersubject intersession reproducibilities. No differences in
      peak and mean WSR were found between the left and the right CCA in the male group
      as well as in the female group. Mean WSS was similar in males (1.3 +/- 0.3 Pa)
      and in females (1.2 +/- 0.2 Pa), but peak WSS was slightly, but significantly,
      higher in males (4.3 +/- 1.3 Pa) than in females (3.3 +/- 0.7 Pa). It can be
      concluded that peak and mean WSR can be reliably determined noninvasively using
      ultrasound.

PMID- 9232768
TI  - Rapid measurement of the spatial resolution of colour flow scanners.
AB  - An acoustic grid for rapid measurement of the spatial resolution of colour
      velocity images is described. The grid is composed of alternate widths of
      acoustic window and acoustic attenuator. Attenuation is provided by the use of a
      layer of waterproof paper, which is wrapped in close contact with a tube of a
      flow phantom. The colour image consists of several closely spaced lines. When the
      grid line spacing is less than the spatial resolution, the colour lines cannot be
      separately visualised. The use of several grids of different spacing provides a
      measure of the spatial resolution. It is shown that the spatial resolution is
      dependent on the position of the focal zone.

PMID- 9232769
TI  - Performance of a miniature magnetic position sensor for three-dimensional
      ultrasound imaging.
AB  - A miniature magnetic position sensor used for three-dimensional ultrasound
      imaging was tested for precision and accuracy in vitro. The sensor alone was able
      to locate points with root-mean-square (rms) uncertainty of 1.7 mm and accuracy
      of 0.05 +/- 0.62 mm over its specified operating range of 50 cm. With an
      ultrasound imaging system, a point was located from arbitrary viewing windows
      with 2.4-mm rms uncertainty and 0.06 +/- 0.68 mm accuracy. If viewing windows
      were limited to those representative of a typical ultrasound examination, the
      system could achieve rms uncertainty in point location of < 1 mm. Performance was
      not affected by operation of the imaging system when the sensor was mounted on an
      ultrasound scanhead. Sensitivity to metals in the operating environment was also
      measured.

PMID- 9232770
TI  - Minimal static excess pressure minimises the effect of extracorporeal shock waves
      on cells and reduces it on gallstones.
AB  - The effects of extracorporeal shock waves on haemoglobin release, membrane
      permeabilisation and stone fragmentation were examined at minimal static excess
      pressures. Shock waves from an electrohydraulic lithotripter were applied at 15,
      20 and 25 kV to red blood cells in plastic pipettes pressurised with 0, 30, 50,
      75, 100, 200, 300 and 400 kPa of static excess pressure; the freed haemoglobin
      was determined as a marker of cell destruction. Using 15-kV discharges, 30-kPa
      excess pressure reduced the freed haemoglobin from 1.21 g/L at ambient pressure
      to 0.39 g/L, 20-kV discharges reduced it from 2.01 g/L to 0.92 g/ L and 25-kV
      discharges from 2.56 g/L to 1.61 g/L. Haemoglobin values at 400-kPa excess
      pressure were reduced to 0.03 g/L (15-kV discharges), 0.07 g/L (20-kV discharges)
      and 0.09 g/L (25-kV discharges), which is a 95%-97% reduction of the values
      obtained at ambient pressure. There was a steep initial drop from 30-100 kPa
      excess pressure followed by a plateau at low level. Propidium iodide uptake by
      L1210 tumour cells, a marker for transient membrane permeabilisation by shock
      waves, was reduced by 90% at these slight excess pressures. Stone fragmentation
      was also suppressed by excess pressure yet not as markedly as at cells; 100 kPa
      reduced the amount of gallstone fragments by 20%, and 400 kPa reduced it by 65%.
      A further reduction, by 93%, was obtained when 1-MPa excess pressure was applied
      to gallstones in a Plexiglas cylinder. Shock wave-gas bubble interaction has been
      previously proposed to mediate the shock wave action. It is suggested that the
      excess pressure reduced the size or number of the bubbles, thus reducing this
      interaction, at least in the case of the cellular effects. The reduced effect of
      shock waves on cells, in contrast to the effect on stones, might open up a new
      approach to the design of lithotripters that would reduce tissue damage yet keep
      fragmentation up at a similar level.

PMID- 9232772
TI  - Ultrasonically induced hemolysis at high cell and gas body concentrations in a
      thin-disc exposure chamber.
AB  - Ultrasound image contrast may be enhanced by injecting gas bodies into the blood.
      This in vitro study was undertaken to assess the potential for induction of
      hemolysis due to ultrasonic activation of the contrast agent gas bodies. Canine
      whole blood with Albunex (Mallinckrodt Medical, St. Louis, MO, USA) was exposed
      to near-field ultrasound beams in 1-mm-thick chambers held stationary (i.e., not
      rotated) in a 37 degrees C water bath. At 2.25 MHz, statistically significant
      hemolysis occurred in 0.5 hematocrit, 50% Albunex suspensions for 0.28-MPa, 1-s
      continuous exposure and for 0.58-MPa, 100-s exposures with 10-microsecond pulses
      and 1.0-ms pulse repetition period. Continuous exposure durations as short as 10
      ms produced about 4.5% hemolysis, which only increased slightly to about 5.5%
      after 100 s. At a constant 1.6 MPa, hemolysis increased with increasing gas body
      concentration and with decreasing cell concentration. Hemolysis decreased with
      increasing frequency in a 50/50 mixture of whole blood and Albunex, with
      thresholds rising from 0.12 MPa continuous (1 s) and 0.47 MPa pulsed (10
      microseconds:1.0 ms for 100 s) at 1.06 MHz to 0.47 MPa continuous and 1.9 MPa
      pulsed at 5.3 MHz.

PMID- 9232771
TI  - Correlation of ultrasound-induced hemolysis with cavitation detector output in
      vitro.
AB  - A 20-MHz passive acoustic detector was used to quantify the amount of transient
      acoustic cavitation occurring in a sample exposed to intense pulsed ultrasound. A
      dilute suspension of human erythrocytes with and without a microbubble echo
      contrast agent was exposed in vitro to 500 W/cm2 (SPPA) ultrasound of center
      frequency 1 MHz and tone burst duration 20, 100, 200, 500 and 1000 microseconds
      at a pulse repetition frequency of 20 Hz. Inertial cavitation occurring within
      the sample, as measured by the temporal average of the detector output,
      correlated well with hemolysis, suggesting that violent bubble collapse is
      responsible for cell damage. The result also raises the prospect of cavitation
      monitoring as a possible predictor of adverse bioeffects when echo-contrast
      agents are used clinically.

PMID- 9232773
TI  - Comparative sensitivity of human erythrocytes and lymphocytes to sonolysis by 1
      MHz ultrasound.
AB  - Many studies of ultrasonic hemolysis have used erythrocytes; other blood cells
      are less well studied. The hypothesis tested was that human lymphocytes, being
      large and relatively fragile, are more sensitive to sonolysis than are
      erythrocytes at equivalent cell concentrations. Human lymphocytes (RPMI 1788)
      grown in vitro and erythrocytes obtained by venipuncture were used at a nominal
      cell concentration of 2.5 x 10(6) cells/mL. Cells were contained in rotated (200
      rpm) exposure vessels and were exposed/sham-exposed to 1-MHz continuous-wave
      ultrasound for 60 s. Cell lysis was determined by hemacytometer counts of
      aliquots taken before/after treatment. The hypothesis was supported; the mean
      levels of lysis in insonated lymphocyte and erythrocyte preparations were 89.8%
      +/- 0.6% and 78.9% +/- 3.1%, respectively. This difference was significant at p <
      0.005.

PMID- 9232774
TI  - The effects of hypertonic saline in healthy and diseased animals.
AB  - In this review, the pharmacological effects of administering hypertonic solutions
      to both healthy animals and during experimentally induced diseases are considered
      with a view to understanding the mechanisms behind the possible clinical efficacy
      of such treatment. The review focuses successively on haemorrhagic shock,
      endotoxic shock and hypokalaemic metabolic alkalosis. How hypertonic saline
      solutions affect oxygen transport by haemoglobin is also considered.

PMID- 9232775
TI  - Effect of gossypol on hepatic and serum gamma-glutamyltransferase activity in
      rats.
AB  - A single intraperitoneal dose (25 mg/kg) of gossypol given to male Sprague-Dawley
      rats caused marked changes in the activity of the hepatic and serum gamma
      glutamyltransferase (GGT) and microsomal monooxygenases. The GGT activity in
      liver homogenate, S-9 supernatant fraction and microsomes was significantly
      depressed; however, the level of serum GGT was elevated. While the hepatic
      glutathione concentration was not greatly changed, the aminopyrine N-demethylase
      activity and microsomal cytochrome P450 content of the liver were significantly
      decreased in the treated rats. At necropsy, the livers of the treated rats
      appeared generally pale with distinct pinpoint foci. Histopathological
      examination of the liver showed degenerative changes and coagulative necrosis.
      The results indicate that gossypol is a strong hepatotoxic agent which can
      produce severe hepatic damage.

PMID- 9232776
TI  - Electrophoretic detection of myeloperoxidase, protease, lactoferrin and lysozyme
      in buffalo polymorphonuclear granular acid extracts.
AB  - Polymorphonuclear (PMN) cells of more than 90% viability and 92% purity were
      isolated from the peripheral blood of buffaloes. The cationic proteins were
      extracted with 0.2 mol/L sodium acetate, pH 4.0 from the granules in the PMN and
      subjected to both non-denaturing and denaturing acid urea polyacrylamide gel
      electrophoresis (AUPAGE) for identification of myeloperoxidase (MPO), lysozyme,
      protease activity and lactoferrin. Protease was identified using alpha-naphthyl
      acetate as substrate, while lactoferrin was identified using a reference
      lactoferrin from bovine milk in AUPAGE, and by double immunodiffusion and Western
      blot techniques. Based on AUPAGE, lysozyme was found to be most cationic of all
      the proteins and peptides from the PMN granules as was evident from reference
      lysozyme run. The results indicated that the granules in buffalo PMN cells have
      lysozyme, protease, MPO and lactoferrin.

PMID- 9232777
TI  - Metabolism of saponins from Narthecium ossifragum--a plant implicated in the
      aetiology of alveld, a hepatogenous photosensitization of sheep.
AB  - One sheep was dosed over 4 consecutive days with 2.1 kg of leaves and flower
      stems of Narthecium ossifragum before it was killed. Sarsasapogenin and
      smilagenin glycosides, in the ratio 9:1, were the dominant saponins present in
      the dosed plant material. GC-MS analyses of the free and conjugated sapogenin
      content of samples recovered from the sheep identified three distinct regions of
      metabolic activity. In the first metabolic region, in the rumen and omasum, the
      ingested plant saponins were hydrolysed to the parent sapogenins, before being
      oxidized at C-3 and reduced to give the epi analogues of the ingested sapogenins.
      The second metabolic region consisted of the duodenum, jejunum, the liver and
      associated ducts. Sapogenins appear to be absorbed in the jejunum and may be
      transported via the portal vein to the liver, where 3 alpha-OH-5 beta-H
      sapogenins (epismilagenin and episarsasapogenin), but not 3 beta-OH-5 alpha-H
      sapogenins (smilagenin and sarsasapogenin), are conjugated and excreted into the
      bile as episarsasapogenin and epismilagenin conjugates in the ratio 4:1. In the
      third metabolic region, in the caecum and the colon, the epi-sapogenin conjugates
      were hydrolysed to free epi-sapogenins. The absence of free and/or conjugated
      sapogenins in urine, collected 24 h after dosing commenced, indicates that
      saponins and their metabolites are not likely to be implicated in the kidney
      disease occurring in ruminants ingesting N. ossifragum.

PMID- 9232778
TI  - Experimental detection of canine haemoglobin (occult blood) in canine faeces by
      reversed passive latex agglutination.
AB  - A reversed passive latex agglutination test (RPLA) using anti-canine haemoglobin
      (Hb) antibody was developed for detecting bleeding in the lower digestive organs
      in dogs, and its applicability as a simple test for faecal occult blood was
      assessed. In Ouchterlony's gel immunodiffusion test, the anti-canine Hb antibody
      used to sensitize the latex reacted with canine Hb but not with Hbs, plasmas or
      meat extracts from pigs, goats, sheep, cattle, horses or chickens, or with fish
      extracts. Using latex sensitized with 50 micrograms/mg of anti-canine Hb IgG
      antibody, the lowest limit of detection for canine Hb was 21 micrograms/ml, and
      the latex reacted negatively with all test specimens other than canine Hb. In an
      in vitro experiment with a mixture of canine faeces and erythrocytes, the
      antigenicity of the Hb was found to undergo only very slight changes even when
      the specimens were allowed to stand for 12 h at room temperature. Hb could not be
      detected by RPLA in any of four successive faecal samples from three experimental
      dogs after infusion of autologous blood (5, 3 or 1 ml) into the stomach. In 3
      other experimental dogs given an infusion of autologous blood (5, 3 or 1 ml) into
      the ascending colon, the presence of Hb was confirmed by RPLA in all four
      successive faecal samples obtained from those which received 5 or 3 ml of blood
      and in all except that obtained following the first defecation from the animal
      which had received 1 ml of blood.

PMID- 9232779
TI  - A serological survey of feline immunodeficiency virus and Toxoplasma gondii in
      stray cats.

PMID- 9232781
TI  - Canine tumour suppressor gene p53--mutation in a case of adenoma of circumanal
      glands.
AB  - Highly conserved regions of the tumour suppressor gene p53, including the typical
      human tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were
      investigated in various canine neoplasms. A mutation CGG-->TGG (arginine-
      >tryptophan) was detected in codon 249 in an adenoma of the circumanal gland.

PMID- 9232780
TI  - The effect of the acute-phase response on in vitro drug metabolism and plasma
      protein binding in the horse.
AB  - The effect of the acute-phase response (APR) on the activity of the hepatic drug
      metabolizing system (DMS) and on the binding of phenylbutazone to plasma proteins
      was investigated in the horse. An APR was induced by intramuscular injections of
      Freund's complete adjuvant in five horses and, five days later, these horses
      together with five clinically normal horses were shot and the right ventral lobe
      of each liver removed. The hepatic microsomal fractions from the liver samples
      were isolated and significantly lower (p < 0.01) concentrations of cytochromes
      P450 and b5 and activities of aniline-p-hydroxylase and aminopyrine N-demethylase
      (43%, 55%, 45% and 30%, respectively) were measured in the livers from the
      adjuvant-inflamed horses, compared to the controls. Phenylbutazone (PBZ) was
      administered intravenously (4.4 mg/kg) to a further four horses and plasma
      protein binding was measured by ultracentrifugation. Five weeks later, these
      horses were injected with Freund's complete adjuvant and the intravenous
      administration of PBZ (4.4 mg/kg) was repeated. Inflammation induced a
      significant increase (p < 0.01) in the unbound fraction of PBZ (5.2 +/- 0.5 as
      against 1.4 +/- 0.6%). These results suggest that the APR depresses the hepatic
      DMS and reduces the binding of PBZ to plasma proteins.

PMID- 9232782
TI  - An apparent effect of immunopotentiation during late gestation on the postpartum
      reproductive performance of Nili-Ravi buffaloes (Bubalus bubalis).
AB  - Thirty-two Nili-Ravi buffaloes were used to determine the effect of prepartum
      immunopotentiation in late gestation with levamisole hydrochloride (0.5 mg/kg),
      vitamin E+selenium (vitE-Se) (Etosol-SE, 10 ml intramuscularly) or Bacille
      Calmette Guerin (BCG) (0.5 ml/animal, subcutaneously) on postpartum reproductive
      performance. The immunopotentiating treatment was given twice, with treatments
      one week apart, approximately 80 days prior to the expected date of parturition.
      Prepartum treatment with vitE-Se or BCG significantly (p < 0.05) reduced the
      calving to first oestrus interval and the length of the postpartum service period
      compared to the control group. The uterine involution period was significantly
      shorter in buffaloes treated with vitE-Se compared to the control group.
      Levamisole hydrochloride apparently improved the reproductive performance, but
      this result was not statistically significant.

PMID- 9232783
TI  - Surgical excision of soft tissue fibrosarcomas in cats.
AB  - OBJECTIVE: The purpose of this study was to determine the tumor-free interval and
      survival times of cats who had one (group 1) or more (group 2) surgeries, or
      surgery and radiation therapy (RTH) (group 3) for treatment of soft tissue
      fibrosarcomas (FSA). STUDY DESIGN: Retrospective study. ANIMALS OR SAMPLE
      POPULATION: 45 client-owned cats. METHODS: Medical records of cats with soft
      tissue FSA were examined. Vaccination and feline leukemia virus (FeLV) status,
      age, sex, breed, tumor location, number of surgeries, completeness of excision,
      and histopathological grade were evaluated to correlate with tumor-free interval
      and survival periods. RESULTS: Overall median tumor-free interval and survival
      times were 10 and 11.5 (range, 1 to 40) months. Median tumor-free interval and
      survival times were more than 16 months each in group 1, more than 5 and 13
      months in group 2, and 4.5 and 9 months in group 3. Age, sex, breed, vaccination
      or FeLV status, tumor location, or histopathological grade did not affect median
      tumor-free interval or survival times (P > .05). Cats with complete excisions had
      significantly longer median tumor-free interval (> 16 versus 4 months) and
      survival time (> 16 versus 9 months) than those with incomplete excisions (P =
      .008). Radiation therapy did not seem to extend tumor-free interval and survival
      times (P = .013). However, most group 3 cats had incomplete surgical excisions,
      resulting in recurrent or progressive disease. CONCLUSIONS: Complete surgical
      excision of FSA in cats is possible and can be curative. CLINICAL RELEVANCE:
      Aggressive surgical excision with wide margins appears to contribute to extended
      tumor-free interval and survival times in cats with soft tissue FSA. Controlled
      prospective studies are needed to determine the efficacy of RTH in treatment.

PMID- 9232784
TI  - Use of colostomy to manage rectal disease in dogs.
AB  - OBJECTIVE: The purpose of this study was to develop a diverting colostomy
      technique for use in dogs. STUDY DESIGN: Clinical case series. ANIMALS: Five
      client-owned dogs presented for diseases requiring diverting colostomy during
      treatment. METHODS: Diverting colostomy was performed in five dogs. A ventral
      approach was used in the first dog and the colon was exteriorized adjacent to the
      linea alba. The technique used in the next four dogs involved creation of a left
      flank rod-supported loop colostomy in which the colon was exteriorized through a
      muscle-separating flank approach to the abdomen. RESULTS: Peritoneal leakage of
      fecal material resulted in the perioperative death of the first dog. The flank
      colostomies were maintained for times ranging form 3.5 weeks to 7 months. No
      major complications were observed, but skin excoriation occurred occasionally
      around the stoma sites in all dogs. CONCLUSION: Diverting colostomy is a
      technique that is suitable for use in treatment of dogs with obstruction or
      leakage involving the distal colon or rectum.

PMID- 9232785
TI  - Intestinal entrapment and strangulation caused by rupture of the duodenocolic
      ligament in four dogs.
AB  - OBJECTIVE: The purpose of this study was to describe four dogs with intestinal
      entrapment and strangulation caused by a rupture of the duodenocolic ligament.
      STUDY DESIGN: This case series documents historical findings, physical
      examination findings, diagnostic workup, surgical intervention, and outcome of
      four dogs confirmed at surgery with duodenocolic ligament rupture. RESULTS: Three
      of four dogs were German shepherds, and two of three German shepherds were intact
      males. The history, clinical signs, and physical examination findings were not
      specific for intestinal entrapment. The clinical signs in three of four dogs
      included chronic vomiting, diarrhea, anorexia, and lethargy. In the remaining
      dog, the clinical signs were vomiting and peracute collapse. This dog rapidly
      deteriorated over a few hours because of strangulation of the entrapped
      intestines. In two of four dogs, abdominal radiographs showed a distended colon
      displaced to the right side of the abdominal cavity. Surgery involved transection
      of the remaining ventral remnant of the duodenocolic ligament and replacing the
      colon into its normal anatomic position. The three dogs with chronic clinical
      signs were either still alive, or were euthanatized for unrelated problems. The
      dog with strangulation of the entrapped intestines was euthanatized at the time
      of surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Duodenocolic ligament rupture
      with secondary bowel entrapment can occur in dogs. The prognosis for these
      animals is favorable provided there is no vascular compromise of the entrapped
      bowel segments. The peracute history, progression of the disease process, and
      outcome of the fourth dog in this study indicate that surgery should be performed
      as an emergency procedure.

PMID- 9232786
TI  - Deep hypothermic low flow cardiopulmonary bypass in small dogs.
AB  - OBJECTIVE: To evaluate the feasibility of and morbidity and mortality associated
      with cardiopulmonary bypass (CPB) using deep hypothermia and low flow perfusion
      in adult dogs weighing less than 10 kg. STUDY DESIGN: Prospective, descriptive
      study. ANIMALS: Two groups of three dogs underwent CPB. Group 1 dogs underwent
      deep hypothermia (15 to 18 degrees C), 45 minutes of low perfusion flow (20
      mL/kg/min) and 1 hour of aortic cross clamp time. In group 2, ultrafiltration of
      perfusate before discontinuation of bypass was added to the standard treatment.
      Complete blood counts, serum biochemistry, urine output, ejection fraction, and
      cardiac output were monitored before and for 7 days after surgery. RESULTS: All
      dogs were successfully weaned from bypass. Four of six dogs survived, three
      without major complications. One dog developed and recovered from septic
      pleuritis. Two dogs died or were euthanatized after surgery because of
      respiratory or gastrointestinal complications. Minor complications included
      anemia, hypoproteinemia, and electrolyte disturbances. Transfusion requirements
      and edema formation were reduced by ultrafiltration. CONCLUSIONS: The
      observations in this study support the feasibility of low flow hypothermic CPB.
      Meticulous tissue handling, precise equipment, ultrafiltration, and aggressive
      postoperative potassium supplementation are recommended for smaller patients.
      CLINICAL RELEVANCE: Increased sensitivity to adverse sequelae of CPB may be
      associated with small patient size. Further evaluation is necessary before
      routine clinical application of low flow hypothermic CPB in this patient
      population.

PMID- 9232787
TI  - Dissipation of heat during polymerization of acrylics used for external skeletal
      fixator connecting bars.
AB  - OBJECTIVE: To determine the amount of heat conducted by transfixation
      intramedullary pins (IP) and Kirschner wires (KW) during polymerization of
      acrylics used for external skeletal fixator (ESF) connecting bars. STUDY DESIGN:
      Thermal conduction was measured using thermistors applied to IP and KW surfaces
      during the polymerization phase of acrylics. METHODS: Type II ESF were created
      from IP or KW placed into wooden dowels and plastic tubing used to create
      connecting bars filled with one of two types of acrylic (Acrylic Pin External
      Fixation System or Technovit, Jorgensen Laboratories, Loveland, CO). Thermistors
      were positioned on the acrylic column surface and on IP or KW surfaces 5 or 10 mm
      from the acrylic column. Five ESF test groups were created. The maximum
      temperature (Tmax) of the acrylic column (Tmax-A), IP (Tmax-IP), KW (Tmax-KW),
      and duration that Tmax-IP or Tmax-KW remained greater than or equal to 55 degrees
      C were calculated. RESULTS: All IP and KW thermistors placed 5 mm from acrylic
      columns reached mean temperatures greater than 50 degrees C and had peak
      temperature ranges greater than 55 degrees C compared with all IP and KW
      thermistors placed 10 mm from the acrylic columns in all groups. Thermistors
      placed 5 mm from the acrylic column in two groups maintained temperatures greater
      than 55 degrees C for greater than or equal to 0.5 minute. CONCLUSIONS: Acrylic
      columns positioned 5 mm from a thermistor on a IP or KW had the potential to
      reach or exceed temperatures that have been reported to cause thermal necrosis of
      tissues. CLINICAL RELEVANCE: Acrylic Pin External Fixation System or Technovit
      acrylic connecting bars used in ESF designs have the potential to cause thermal
      injury to soft and bony tissue by thermal conduction along transfixation pins or
      wires.

PMID- 9232788
TI  - Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical
      technique.
AB  - OBJECTIVE: Assessment of a microsurgical technique for transsphenoidal
      hypophysectomy in dogs. STUDY DESIGN: Prospective study using physical
      examination, pituitary function testing, computed tomography (CT), and
      histological examination at autopsy. ANIMALS OR SAMPLE POPULATION: Eight
      laboratory beagle dogs. METHODS: Pituitary function was assessed before and at 10
      weeks after hypophysectomy by combined administration of four releasing hormones
      (anterior pituitary), administration of haloperidol (pars intermedia), and
      infusion of hypertonic saline (posterior pituitary). RESULTS: CT imaging enabled
      accurate preoperative localization of the pituitary. Appropriate positioning and
      surgical technique facilitated exposure of the pituitary and its extraction
      without hemorrhage. Postoperative recovery was generally uncomplicated. None of
      the eight dogs had somatotropic, gonadotropic, lactotropic, melanotropic, or
      posterior pituitary responses to stimulation at 10 weeks after hypophysectomy.
      Four dogs (ACTH nonresponders) also had no corticotropic response and four (ACTH
      responders) had small but significant responses in the combined anterior
      pituitary function test. Adrenocortical atrophy was more pronounced in the ACTH
      nonresponders than in the responders. No residual pituitary tissue was found
      along the ventral hypothalamic diencephalon but nests of pituitary cells were
      found embedded in fibrous tissue in the sella turcica. CONCLUSIONS: The surgical
      technique proved to be safe and effective. Microscopic nests of pituitary cells
      in the sella turcica may be responsible for residual corticotropic response to
      hypophysiotropic stimulation after hypophysectomy. CLINICAL RELEVANCE: The
      surgical technique may be used in the treatment of dogs with pituitary-dependent
      hyperadrenocorticism. The corticotropic response is the most sensitive criterion
      in assessing completeness of hypophysectomy in dogs.

PMID- 9232789
TI  - Mechanical characteristics and comparisons of cerclage wires: introduction of the
      double-wrap and loop/twist tying methods.
AB  - OBJECTIVE: Evaluate the mechanical properties of twist, loop, double loop, double
      wrap and loop/twist cerclage. METHODS: The initial tension generated by 18
      cerclage of each type was determined using a materials testing machine after
      tying around a testing jig. Six wires from each type were distracted and the
      initial stiffness and yield load were determined. Yield behavior was further
      investigated in six wires of each type by determining the load required to reduce
      cerclage tension below 30 Newton (N) following and incremental (50 N) stepwise
      load and unload regimen. The amount of collapse of the simulated bone fragments
      that resulted in the reduction of initial tension to 30 N was measured for the
      final six wires of each group. Data were analyzed by analysis of variance and a
      multiple comparison test. RESULTS: Twist type cerclage generated less tension
      than loop-type cerclage. The yield load of these two types was similar. Double
      loop and double-wrap cerclage generated superior tension and resisted a greater
      load before loosening. Loop/twist cerclage had an intermediate initial tension
      but had the greatest resistance to loading. In the collapse test, the greater the
      initial tension, the more collapse could occur before the wire was loose. For all
      types of cerclage wire fixation, a reduction of diameter of the testing jig of
      more than 1% caused loosening. CLINICAL RELEVANCE: Double-loop and double-wrap
      cerclage provide greater compression of fragments and resist loads associated
      with weight-bearing better than the twist and loop methods. Loop/twist cerclage
      may have advantages because of their superior resistance to loading. All cerclage
      will loosen if fracture fragments collapse.

PMID- 9232790
TI  - Application of ventral pins and polymethylmethacrylate for the management of
      atlantoaxial instability: results in nine dogs.
AB  - OBJECTIVE: The purpose of this report was to determine the efficacy of the
      application of ventral pins and polymethylmethacrylate for the management of
      congenital and traumatic atlantoaxial instability (AAI) in dogs. STUDY DESIGN:
      Medical records and radiographs of nine dogs with AAI were reviewed for
      neurological deficits, clinical diagnosis, surgical technique, and long-term
      outcome. SAMPLE POPULATION: Six toy breed dogs with congenital AAI and three
      medium or large breed dogs with traumatic AAI were identified for inclusion in
      the study. METHODS: The atlantoaxial joints of nine dogs with AAI were surgically
      stabilized using ventral application of pins and polymethylmethacrylate. Follow
      up evaluation for resolution of clinical signs and possible complications of
      surgery was performed in all dogs. The median follow-up time for surviving dogs
      (8) was 11.5 months with a mean of 13 months. RESULTS: An excellent outcome was
      identified in five patients. Three dogs had a good outcome and one dog died of
      respiratory complications. Cervical pain was eliminated or significantly reduced
      in all dogs that survived and none of the dogs had major residual neurological
      deficits. CONCLUSIONS: Arthrodesis could not be confirmed on follow-up
      radiographs due to the presence of the polymethylmethacrylate; however, adequate
      stabilization of C1-C2 appears to have been achieved based on the resolution of
      clinical signs. CLINICAL RELEVANCE: Application of ventral pins and
      polymethylmethacrylate is an effective means of surgical treatment for congenital
      and traumatic AAI.

PMID- 9232791
TI  - Laparoscopic cryptorchidectomy in standing horses.
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of using
      laparoscopy to remove cryptorchid testes from standing horses. STUDY DESIGN:
      Prospective clinical study. ANIMALS OR SAMPLE POPULATION: Eleven client-owned
      horses ranging in age from 4 months to 2 years. METHODS: Abdominal insufflation
      was initiated and maintained using a 20 F insufflation tube, attached via a
      stopcock, to the low pressure regulator on a standard carbon dioxide pressure
      tank. After trocar and laparoscope placement in the ipsilateral flank the testes
      were identified. Local anesthesia of the structures to be manipulated was
      administered through the instrument channel on the operative laparoscope, using a
      catheter with a needle attached. Testes were grasped with large laparoscopic
      forceps and exteriorized through the abdominal wall. Ligation and transection of
      the mesorchium was extracorporeal. The descended testes were removed using a
      standard standing technique. RESULTS: Complications were minor, including mild
      colic in one horse. The mean surgical time for standing laparoscopic
      cryptorchidectomy and castration of these colts was 58.9 +/- 24.3 minutes.
      CONCLUSIONS AND CLINICAL RELEVANCE: Standing laparoscopic cryptorchidectomy,
      using the instrumentation described, is a safe and practical technique in young
      horses.

PMID- 9232792
TI  - Cosmetic dehorning in goats.
AB  - OBJECTIVE: This article describes a technique using primary closure when
      dehorning goats, and report the results of 22 cases. STUDY DESIGN: Medical
      records of goats that had cosmetic dehorning were reviewed. ANIMALS OR SAMPLE
      POPULATION: Twenty-two goats. METHODS: The medical records of 22 goats, not
      previously dehorned by other methods, that were cosmetically dehorned between
      January 1988 and September 1995 were reviewed. Data retrieved from the medical
      record included age, breed, sex, surgical technique used for dehorning, and any
      complications that occurred after surgery. All clients were contacted by
      telephone to determine the course of postoperative healing for each goat. A
      surgical technique to remove the horns and close the defect primarily was
      described. RESULTS: The mean age of the goats, all male Nubian or Nubian-Spanish
      cross, was 6.9 months (range, 2 to 24 months). Horn base diameter ranged from
      approximately 2 to 4 cm. Mean time from surgery until follow-up was 12.9 months
      (range, 3 to 57 months). All incisions healed by first intention in 10 to 14
      days. Clinical signs of sinusitis were not noted, and owners were pleased with
      the healing time and cosmetic result obtained. CONCLUSIONS: Primary closure of
      skin defects after dehorning of goats can be achieved with minimal postoperative
      care and excellent cosmetic appearance. CLINICAL RELEVANCE: Primary closure after
      dehorning in mature goats reduces aftercare.

PMID- 9232793
TI  - Laparoscopic cryptorchid castration in standing horses.
AB  - OBJECTIVE: This article describes a new technique for laparoscopic cryptorchid
      castration in standing horses. STUDY DESIGN: Prospective study. ANIMALS OR SAMPLE
      POPULATION: Eight horses aged 11 months to 3 years and weighing between 300 and
      643 kg. METHODS: Food was withheld for 24 to 36 hours, and then horses were
      sedated with detomidine HCl (0.02 to 0.03 mg/kg) and butorphanol tartrate (0.02
      mg/kg). The paralumbar fossa region was desensitized with 2% mepivacaine in an
      inverted "L" pattern and caudal epidural anesthesia was administered with either
      xylazine (0.18 mg/kg diluted to 10 to 15 mL with 0.9% sodium chloride) or a
      combination of 2% mepivacaine and xylazine (0.18 mg/kg). Initial laparoscopic
      exploration was performed from the left flank; in three horses, right flank
      laparoscopy was needed to complete the procedure. The spermatic cord was ligated
      within the abdomen with one or two sutures of 0 polydioxanone suture, and the
      testis or testes removed through a flank incision. RESULTS: In five horses with
      no palpably descended testes, standing laparoscopy was the only procedure
      performed, whereas in two horses, the abdominal testis was removed
      laparoscopically, and the descended testis was removed under short acting
      anesthesia. In one horse, with nonpalpable testes, it was determined by
      laparoscopic observation that the testes were in the inguinal canal, and
      castration was performed under general anesthesia. No surgical or postoperative
      complications were noted. The right side of the abdomen, and especially the right
      vaginal ring, could be easily observed from the left side by passing the
      laparoscope through a small perforation in the mesocolon of the descending colon
      or by elevating the descending colon with an instrument or by use of an arm in
      the rectum. CONCLUSIONS: The standing laparoscopic approach combined with or
      without short-acting anesthesia to remove the descended testis is easily
      performed. CLINICAL RELEVANCE: This approach will provide surgeons with another
      option to castrate cryptorchid stallions.

PMID- 9232794
TI  - Nasal septoplasty for correction of septal deviation in a foal.
AB  - OBJECTIVE: This article reports an alternative to septal resection in nasal
      septal deviations involving the rostral 7 to 10 cm of the nasal septum. STUDY
      DESIGN: Case report. SAMPLE POPULATION: One client-owned foal. METHODS: A nasal
      approach with mucosal elevation was used to gain access to the cartilaginous
      portion of the nasal septum. Once exposed, a series of parasagittal incisions in
      the cartilage allowed the septum to be repositioned while providing some
      intrinsic stabilization. RESULTS: The nasal approach provided good access to the
      rostral 7 cm of the nasal septum. The technique resulted in minimal hemorrhage
      from the site. Bleeding was reduced with the use of ephedrine to vasoconstrict
      the mucosal vessels, and primary closure of the mucosa. CONCLUSIONS: Use of an
      intrinsically stabilized septoplasty should be considered as a means of
      decreasing the airway obstruction caused by nasal septal deviation in foals while
      allowing for normal development of facial contour.

PMID- 9232795
TI  - Evaluation of an oscillometric blood pressure monitor on anesthetized cats and
      the effect of cuff placement and fur on accuracy.
AB  - OBJECTIVES: (1) To determine the usefulness of one specific oscillometric monitor
      for making indirect measurements of arterial pressure in cats. (2) To determine
      the difference between two specific cuff placement sites. (3) To determine if
      clipping the hair beneath the cuff has an affect on the accuracy of oscillometric
      blood pressure determination. STUDY DESIGN: Prospective study comparing the
      accuracy of the Datascope Passport (Datascope Corp, Paramus, NJ) with concurrent
      invasive measurements. ANIMALS: Six anesthetized domestic felines weighing 4.5 to
      5 kg. METHODS: The direct arterial pressure was measured using a cannula placed
      in the right common carotid artery. Oscillometric cuffs of appropriate size were
      placed on both thoracic limbs distal to the elbow and both pelvic limbs distal to
      the stifle. The hair in the areas of cuff placement on the right limbs was
      clipped circumferentially. Measurements of systolic, diastolic, and mean arterial
      pressure (MAP) were taken for each site during normotension, hypotension, and
      hypertension. Comparisons between indirect and direct measurements were made
      using a parametric analysis of method comparison. RESULTS: No significant
      differences were noted when the clipped limbs were compared with the
      corresponding limbs which were left unclipped (P > .378) or when the thoracic
      limb measurements were compared with those of the pelvic limb (P > .088). There
      were significant differences (P < or = .002) between the two pressure measurement
      methods for the systolic, diastolic, and mean arterial pressures over all three
      pressure ranges. CONCLUSIONS: The Datascope Passport did not accurately estimate
      the invasively measured arterial pressure. CLINICAL RELEVANCE: Use of noninvasive
      blood pressure monitoring equipment is increasing in use in veterinary medicine,
      and the accuracy of one specific monitor is reported.

PMID- 9232796
TI  - Anesthetic potency of desflurane in the horse: determination of the minimum
      alveolar concentration.
AB  - OBJECTIVE: To determine the minimum alveolar concentration (MAC) of desflurane
      (DES) in the horse. STUDY DESIGN: Prospective study. ANIMALS: Six healthy adult
      horses (three males and three females) weighing 370 +/- 16 kg and aged 9 +/- 2
      years old. METHODS: Anesthesia was induced with DES vaporized in oxygen via a
      face mask connected to a large-animal, semiclosed anesthetic circle system. The
      horses were endotracheally intubated and positioned in right lateral recumbency.
      Inspired and end-tidal DES were monitored using a calibrated Ohmeda RGM 5250
      multigas analyzer (Ohmeda-BOC, Spain). The MAC of desflurane that prevented gross
      purposeful movement in response to 60 seconds of noxious electrical stimulation
      of oral mucous membranes was determined. RESULTS: The time from the start of DES
      administration to lateral recumbency was 6.1 +/- 0.9 min. The MAC of DES in these
      horses was 7.6 +/- 0.4%. Time required for the animal to regain sternal
      recumbency after 98 +/- 4 minutes of anesthesia was 6.6 +/- 0.5 minutes and the
      time to standing was 14.3 +/- 2.7 minutes. CONCLUSIONS: The MAC of desflurane in
      these horses was 7.6 +/- 0.4%. DES provided a rapid induction to, and recovery
      from, anesthesia. CLINICAL RELEVANCE: Desflurane offers the potential for more
      precise control during anesthesia, and may allow a faster and uneventful
      recovery. It is important to know the MAC of an inhalant to use it clinically.

PMID- 9232797
TI  - Calmodulin-regulated adenylyl cyclases and neuromodulation.
AB  - Coincidence detection and crosstalk between signal transduction systems play very
      important regulatory roles in the nervous system, particularly in the regulation
      of transcription. Coupling of the Ca2+ and cAMP regulatory systems by calmodulin
      regulated adenylyl cyclases is hypothesized to be important for some forms of
      synaptic plasticity, neuroendocrine function, and olfactory detection. Recent
      studies of a mutant mouse deficient in type I calmodulin-sensitive adenylyl
      cyclase have provided the first evidence that adenylyl cyclases are important for
      synaptic plasticity, as well as for learning and memory in vertebrates.

PMID- 9232798
TI  - Regulation of excitatory and inhibitory neurotransmitter-gated ion channels by
      protein phosphorylation.
AB  - Phosphorylation of ligand-gated ion channels is recognised as a potentially
      important mechanism for short- and long-term modulation of ion-channel function.
      Following the discovery of numerous sites of phosphorylation on ligand-gated ion
      channel proteins, recent studies have demonstrated that neurotransmitter-induced
      activation of serine/threonine, tyrosine and other kinases can result in the
      modulation of glutamate, type A gamma-aminobutyric acid (GABAA) and glycine
      receptors. These findings may have important consequences for our understanding
      of synaptic transmission and neuronal excitability.

PMID- 9232799
TI  - Dendritic signal integration.
AB  - Recent studies have identified various forms of active dendritic signals that may
      contribute to neuronal integration. One of the most remarkable findings is the
      demonstration of highly localized Ca2+ transients that are limited to small
      dendritic segments and even to single dendritic spines. In addition, through use
      of the powerful two-photon excitation imaging technique, it has been possible to
      reveal the existence of dendritic Ca2+ signals under in vivo conditions. Finally,
      active backpropagation of action potentials into dendrites has been shown to
      boost dendritic Ca2+ signals supralinearly and, thus, to contribute to the
      induction of long-term potentiation.

PMID- 9232800
TI  - Synaptic signaling by nitric oxide.
AB  - Endogenous nitric oxide (NO) mediates certain aspects of synaptic plasticity and
      neurotoxicity associated with NMDA-type glutamate receptors. Neuronal NO synthase
      contains a modular protein-protein interaction motif, termed the PDZ domain, that
      links the synthase to a synaptic protein complex containing postsynaptic density
      protein PSD-95 and NMDA receptors. Characterization of this pathway has provided
      new insights into the role of NO in brain physiology and disease.

PMID- 9232801
TI  - PKA isoforms, neural pathways, and behaviour: making the connection.
AB  - In mammals, the cAMP-dependent protein kinase (PKA) family of enzymes is
      assembled from the products of four regulatory and two catalytic subunit genes,
      all of which are expressed in neurons. Specific isoforms of PKA display
      differences in biochemical properties and subcellular localization, but it has
      been difficult to ascribe specific physiological functions to any given isoform.
      The recent development of gene knockout and transgenic mouse models has allowed
      for a more integrated examination of the in vivo roles of specific PKA isoforms
      in gene expression, synaptic plasticity, and behaviour.

PMID- 9232802
TI  - Interaction of ion channels and receptors with PDZ domain proteins.
AB  - The complex anatomy of neurons demands a high degree of functional organization.
      Therefore, membrane receptors and ion channels are often localized to selected
      subcellular sites and coupled to specific signal transduction machineries. PDZ
      domains have come into focus as protein interaction modules that mediate the
      binding of a class of submembraneous proteins to membrane receptors and ion
      channels and thus subserve these organizational aspects. The structures of two
      PDZ domains have been resolved, which has led to a structural understanding of
      the specificity of interactions of various PDZ domains with their respective
      partners. The functional implications of PDZ domain interactions are now being
      addressed in vitro and in vivo.

PMID- 9232803
TI  - The InsP3 receptor and intracellular Ca2+ signaling.
AB  - The inositol 1,4,5-trisphosphate receptor (InsP3R) is a ligand-gated Ca2+-release
      channel on intracellular Ca2+ store sites (such as the endoplasmic reticulum),
      and plays an important role in intracellular Ca2+ signaling in a wide variety of
      cell types. Recent studies have shown that binding of inositol 1,4,5
      trisphosphate (InsP3) to InsP3R isoforms is differentially regulated by Ca2+, and
      that InsP3R functions are finely regulated by phosphorylation via tyrosine
      kinases and protein kinase C, by dephosphorylation via calcineurin, and by
      binding to FKBP (FK506-binding protein). In addition, transient receptor
      potential (TRP) and TRP-like proteins appear to couple conformationally with the
      InsP3R for capacitative Ca2+ entry. The importance of InsP3R signaling in
      neuronal function has been demonstrated by gene targeting in mice and by studies
      of T-cell receptor signaling, apoptosis, meiotic maturation, and cytokinesis.

PMID- 9232804
TI  - Ca2+ and the regulation of neurotransmitter secretion.
AB  - Ca2+ plays an important role in the regulation of multiple steps that contribute
      to neurotransmitter secretion. Electrophysiological approaches have defined the
      nature of the Ca2+ signal and its sites of action, while recent biochemical,
      molecular, and genetic approaches have identified and characterized candidate
      molecular targets for Ca2+ regulation.

PMID- 9232805
TI  - Sequential roles of agrin, MuSK and rapsyn during neuromuscular junction
      formation.
AB  - Formation of the neuromuscular junction requires a series of reciprocal inductive
      interactions between the motor neuron and the muscle cell that culminate in the
      precise juxtaposition of a highly specialized presynaptic nerve terminal with a
      complex postsynaptic endplate on the muscle surface. Although nerve-derived agrin
      has long been thought to play a key role during neuromuscular junction formation,
      the molecular mechanisms underlying its actions are only now coming into focus,
      following the recent discovery that agrin acts via the MuSK receptor tyrosine
      kinase.

PMID- 9232806
TI  - Phosphoinositides as spatial regulators of membrane traffic.
AB  - Inositol phospholipids are a focus of renewed interest with the discovery of
      their unanticipated pivotal roles in membrane trafficking events. Reversible
      phosphorylation of phosphatidylinositol generates spatially localized signals on
      membranes that recruit or activate proteins essential for cell membrane budding,
      fission and fusion. Recent advances have taken place in the characterization of
      lipid kinases and phosphoinositide-regulated effector proteins, and in the
      elucidation of phospholipase D mediated mechanisms involving ADP ribosylation
      factor and Rho family proteins. The roles played by phosphoinositides in aspects
      of secretory granule formation, fusion and endocytosis indicate the importance of
      phosphorylated lipids for neurotransmitter release.

PMID- 9232807
TI  - Ca2+-dependent regulation in neuronal gene expression.
AB  - Ca2+ is an important signal-transduction molecule that plays a role in many
      intracellular signaling pathways. Recent advances have indicated that in neurons,
      Ca2+-controlled signaling mechanisms cooperate in order to discriminate amongst
      incoming cellular inputs. Ca2+-dependent transcriptional events can thereby be
      made selectively responsive to bursts of synaptic activity of specific intensity
      or duration.

PMID- 9232808
TI  - Signalling through the neurotrophin receptor p75NTR.
AB  - Activation specific tyrosine kinase receptors by neurotrophins accounts for the
      longest known biological actions of the neurotrophins, in particular the
      promotion of neuronal survival. However, recent studies have revealed that nerve
      growth factor, the neurotrophin regarded as best understood, also activates a
      signalling pathway by binding to the neurotrophin receptor p75(NTR). This
      receptor belongs to the tumor necrosis factor receptor family and lacks intrinsic
      catalytic activity. The p75(NTR) receptor binds all neurotrophins with nanomolar
      affinity; however, nerve growth factor seems to be uniquely able to activate it,
      causing the death of trkA-negative neurons during normal development. Thus, nerve
      growth factor prevents programmed cell death through its receptor TrkA, but
      promotes it by signalling through p75(NTR).

PMID- 9232809
TI  - Nucleotide receptors.
AB  - Adenosine 5'-triphosphate (ATP) and/or related nucleotides act at both ionotropic
      (P2X) and metabotropic (P2Y) receptors. P2X receptor subunits (P2X1-P2X7) form
      ligand-gated cation channels, as homomultimers or heteromultimers. Recent work
      indicates that P2X3 subunits participate in channels expressed by nociceptive
      sensory neurons, and that the second of the two transmembrane domains of each
      subunit contributes to the ion permeation pathway. P2X7 subunits form large
      cytolytic pores in addition to cation channels; they have been found in
      macrophages and brain microglia. P2Y receptors form a distinct subset of G
      protein-coupled receptors; most couple through G proteins to phospholipase C, but
      inhibition of adenylate cyclase and N-type Ca2+ channels, and activation of K+
      channels also occurs. Expressed P2Y receptors have generally been distinguished
      pharmacologically by the rank order of effectiveness of agonists; some prefer
      pyrimidines to purines. Recent studies suggest that it is important to use
      purified nucleotides in such classifications. Several P2Y receptors have a very
      widespread tissue distribution.

PMID- 9232810
TI  - Cyclic nucleotide gated channels as regulators of CNS development and plasticity.
AB  - Cyclic nucleotide gated (CNG) cation channels are critical for signal
      transduction in vertebrate visual and olfactory systems. Members of the CNG
      channel gene family have now been cloned from a number of species, from
      Caenorhabditis elegans to humans. An important advance has been the discovery
      that CNG channels are present in many neurons of the mammalian brain. CNG
      channels act as molecular links between G-protein-coupled cascades, Ca2+
      signalling systems, and gaseous messenger pathways. Perhaps most striking are
      recent data implicating CNG channels in both developmental and synaptic
      plasticity.

PMID- 9232811
TI  - Synaptic vesicle endocytosis.
AB  - Exocytosis of synaptic vesicles is followed rapidly by reinternalization and
      recycling of their membranes. Recent studies have confirmed the key role of
      clathrin-mediated endocytosis in synaptic vesicle reformation and have identified
      new proteins that participate in this process. In addition, growing evidence
      suggests that lipids, primarily phosphoinositides, play an important role in
      synaptic vesicle recycling.

PMID- 9232813
TI  - Signalling mechanisms. Editorial overview.

PMID- 9232812
TI  - Neurotransmitter release - four years of SNARE complexes.
AB  - Exocytosis in neurons requires proteins known as SNAREs, membrane proteins that
      have now been implicated in many intracellular fusion events. SNAREs assemble
      into stable ternary complexes that are dissociated by the ATPase NSF (N
      ethylmaleimide-sensitive factor), working together with SNAPs (soluble NSF
      attachment proteins). Recent results have shed new light on the mechanisms
      underlying SNARE (SNAP receptor) complex assembly and disassembly, and suggest
      changes in models that relate these reactions to vesicle docking and fusion.

PMID- 9232814
TI  - Web alert. Signalling mechanisms.

PMID- 9232815
TI  - Human skin basement membrane in health and in autoimmune diseases.
AB  - Skin basement membrane zone (BMZ) is an ultrastructurally defined area situated
      between the outer layer of skin, the epidermis, and the inner layer of skin, the
      dermis. The major function of skin BMZ is to serve as an adherent connection
      between the epidermis and the dermis. Heritable skin diseases characterized by
      genetic mutations that result in defective BMZ protein production, such as
      junctional and dystrophic epidermolysis bullosa, manifest clinically as skin
      fragility and subepidermal blister formation inducible by minor trauma. Many
      distinct, yet interconnected BMZ components, have been identified and studied
      extensively. Some of these essential components, interestingly, were discovered
      because they were targeted by an autoimmune reaction. As a result of studying the
      autoimmune diseases, these BMZ components involved in autoimmune reaction, or
      autoantigens, were isolated by molecular biology techniques. The isolation of
      these autoantigens, in turn, facilitates our studies of the normal structures and
      functions of skin BMZ. The skin BMZ can be divided into four ultrastructurally
      distinct areas: the hemidesmosome/upper lamina lucida, the lower lamina lucida,
      the lamina densa, and the sub-lamina densa. Well-characterized BMZ components
      include the hemidesmosome/upper lamina lucida-located bullous pemphigoid antigens
      (BP230 and BP180), a 6b4 integrin, and plectin; the lower lamina lucida-located
      laminin-1, laminin-5 (previously named kalinin, epiligrin, nicein, BM600),
      laminin-6 (previously named k-laminin), p105, and entactin/nidogen; the lamina
      densa-located type IV collagen and perlecan; and the sub-lamina densa-located
      type VII collagen (epidermolysis bullosa acquisita antigen). Mucosal BMZ also
      contain identical components as skin BMZ. Autoantibodies targeting skin and/or
      mucosal BMZ components, like that of genetic mutation of BMZ components, result
      in a histopathologically defined subepidermal blistering disease, that is, a
      blister which occurs just below the epidermis/epithelium. Well-characterized
      autoimmune subepidermal blistering diseases include bullous pemphigoid (BP),
      linear IgA bullous dermatosis, cicatricial pemphigoid (with subsets of patients
      characterized by autoantibodies targeting either BP antigens or laminins), anti
      p105 pemphigoid, and epidermolysis bullosa acquisita. Using a simple method of
      direct or indirect immunofluorescence testing on a skin section chemically
      separated at the middle portion of lamina lucida, in combination with
      immunoelectron microscopy and target antigen determination, accurate diagnoses
      for various autoimmune subepidermal blistering diseases can be obtained.

PMID- 9232816
TI  - Kidney transplantation: a brief review.
AB  - Since the first successful kidney transplant in 1954, results of these
      transplants have dramatically improved. Given refinements in surgical techniques
      and perioperative care, combined with superior immunosuppression, the procedure
      is now the treatment of choice for patients of all ages with ESRD. Acute
      rejection no longer represents a significant threat to graft loss, and the newer
      immunosuppressive drugs will likely diminish this problem further. Complications
      such as sepsis are fewer and more reliably managed with current therapies.
      Chronic rejection remains a major problem whose incidence has not been
      significantly altered. This along with a better understanding of the processes
      that may ultimately lead to graft tolerance will be the major challenges facing
      the field of renal transplantation as it enters the 21st century.

PMID- 9232818
TI  - Origin of metazoan adhesion molecules and adhesion receptors as deduced from cDNA
      analyses in the marine sponge Geodia cydonium: a review.
AB  - The phylogenetic relationships of the kingdom Animalia (Metazoa) have long been
      questioned. Whether the lowest eukaryotic multicellular organisms, the metazoan
      phylum Porifera (sponges), independently evolved multicellularity from a separate
      protist lineage (polyphyly of animals) or whether they were derived from the same
      protist group as the other animal phyla (monophyly) remains unclear. Analyses of
      the genes that are typical for multicellularity, e.g. those coding for adhesion
      molecules (galectin) and adhesion receptors (receptor tyrosine kinase, integrin
      receptor, receptors featuring scavenger receptor cysteine-rich domains) or
      elements involved in signal transduction pathways (G-proteins, Ser/Thr protein
      kinases), especially from the marine sponge Geodia cydonium, indicate that all
      animals, including sponges, are of monophyletic origin.

PMID- 9232819
TI  - Glia in the chiasms and medulla of the Drosophila melanogaster optic lobes.
AB  - Different classes of glia cells in the optic lobes of Drosophila melanogaster
      were defined by the enhancer trap technique, using expression of the lacZ
      reporter gene. At both the outer and inner optic chiasms, there are stacks of
      glia, arrayed from dorsal to ventral, interpersed between the crossings of axonal
      fiber bundles. The giant glial cells of both the outer and inner chiasms are
      similar with respect to their nuclear shapes and positions, indicating similar
      functions of these cell types. Another class of glia is found in the medulla
      neuropil. Their cell bodies anchor in the most distal region of the neuropil, and
      their processes extend into the deeper neuropil layers. Birth dating using BrdU
      shows that both groups of chiasm glia are born early in larval life; they may
      participate in the development of the optic lobe. The medulla glia are born later
      and may be involved primarily in adult functions. In the wild type, and in
      mutants with structurally altered optic lobes, the numbers of tract-associated
      glial cells in the outer and inner optic chiasms seem to vary with the number of
      visual columns, whereas the complement of medulla neuropil glia correlates with
      the volume of the optic lobe.

PMID- 9232820
TI  - Biochemical and histological analysis of two Muller cell antibodies in developing
      and adult cat and rat central nervous system.
AB  - We investigated the binding characteristics of two monoclonal antibodies, 4F3 and
      3F8, which in the retina specifically stain Muller cells, both with protein blots
      and immunohistochemically in sections of various regions of the central nervous
      system of neonatal and adult cats and rats. Clear differences emerged between the
      two antibodies. In addition, some species-specific as well as developmental
      differences within the staining pattern of each individual antibody were evident.
      The epitopes recognized by 4F3 lay mainly in the 57-63 kDa range. Histologically,
      4F3 labelled mainly glia cells: oligodendrocytes and astrocytes in optic nerve,
      astrocytes in neocortex and cerebellum, Bergmann glia in the cerebellum and
      radial glia in neonatal animals. This was confirmed by double-immunofluorescence
      with the astrocyte marker GFAP. By contrast, 3F8 epitopes lay mainly in the 47-49
      kDa range. Histologically, 3F8 labelled oligodendrocytes in the optic nerve, but
      only neurons in cerebellum and neocortex as confirmed by double-labelling with
      neuronal markers. Neither 4F3 nor 3F8 recognized GFAP or vimentin. These results
      clearly indicate (1) that the two antibodies identify new epitopes/molecules, (2)
      that the antigens are not retina-specific, and (3) that Muller cells share
      epitopes with other glial cells as well as with neurons outside the retina.

PMID- 9232821
TI  - Ontogenesis of the retinohypothalamic tract, vasoactive intestinal polypeptide-
      and peptide histidine isoleucine-containing neurons and melatonin binding in the
      hypothalamus of the mink.
AB  - The development of the retinohypothalamic tract (RHT) labeled with cholera toxin
      and of the vasoactive intestinal polypeptide (VIP) and peptide histidine
      isoleucine (PHI) systems was studied in the hypothalamus of neonatal mink by
      using immunohistochemistry. Retinal fibers were observed in the suprachiasmatic
      nucleus (SCN) from birth and were adult-like by day 14. VIP and PHI
      immunoreactivity was also present from birth. Melatonin binding was studied by
      autoradiography using [125I]melatonin as a ligand. A specific binding was
      detected in near-term fetal and neonate brains in the olfactory epithelium,
      various thalamic nuclei, the pineal gland, and the pars tuberalis of the
      pituitary gland, but never in the SCN. These results are discussed in the context
      of the potential role of daylight cycles and/or melatonin in entraining circadian
      rhythms in neonate mink.

PMID- 9232822
TI  - Heterogeneous distribution of neurocalcin-immunoreactive nerve terminals in the
      mouse adrenal medulla.
AB  - Neurocalcin is a novel calcium-binding protein found in bovine brain tissue. We
      investigated immunoreactivity for neurocalcin in the mouse adrenal medulla using
      light and electron microscopy. The immunoreactivity was present in nerve fibers,
      nerve terminals, and ganglion cells in the adrenal medulla, but chromaffin cells,
      sustentacular cells, and Schwann cells were negative in reaction. Nerve bundles
      containing neurocalcin-immunoreactive fibers passed through the adrenal cortex
      and extended into the medulla. Immunopositive nerve fibers branched off and
      projected varicose terminals around the chromaffin cells. These varicose
      terminals contained small and large-cored vesicles and made synapses with the
      chromaffin cells. We performed paraformaldehyde-induced fluorescence
      histochemical studies for catecholamine combined with immunohistochemical studies
      for neurocalcin. Neurocalcin-immunoreactive nerve terminals were more abundant at
      noradrenaline (fluorescent) cell-rich regions than at adrenaline (non
      fluorescent) cell-rich regions. These results show that neurocalcin
      immunoreactive nerves mainly innervate noradrenaline-containing chromaffin cells
      in the mouse adrenal medulla and that neurocalcin may regulate synaptic function
      in the nerve terminals.

PMID- 9232823
TI  - Neuropeptide Y-immunoreactive intracardiac neurones, granule-containing cells and
      nerves associated with ganglia and blood vessels in rat and guinea-pig heart.
AB  - Intrinsic neuropeptide Y-containing neurones in rat and guinea-pig hearts were
      studied at the ultrastructural level by the pre-embedding peroxidase
      antiperoxidase immunocytochemical technique. Intracardiac neuronal cell bodies
      were often weakly or moderately immunostained, and the labelling was usually
      pronounced in the Golgi complex, multivesicular bodies, some cisterns of granular
      endoplasmic reticulum and large granular vesicles. Neuropeptide Y-immunoreactive
      nerve fibres were also observed in association with intracardiac neurones. A
      subpopulation of neuropeptide Y-immunoreactive granule-containing cells in the
      rat heart are described for the first time and were very heavily labelled; other
      granule-containing cells were non-immunoreactive, but were contacted by
      neuropeptide Y-containing nerves. Preterminal regions of nerve fibres that were
      located in nerve bundles were only weakly neuropeptide Y-immunoreactive, in
      contrast to the heavy labelling observed in varicosities that contained many
      synaptic vesicles. Many neuropeptide Y-immunoreactive nerve fibres were
      associated with the coronary vasculature and were particularly prominent in the
      walls of small arteries and arterioles where labelled nerve varicosities were
      present close to the smooth muscle cells. Immunoreactive nerves were also seen in
      the myocardium, usually near to capillaries. In axonal varicosities, the central
      core of large granular vesicles was immunolabelled, and electron-dense
      immunoreactive material outlined the membranes of small and large clear vesicles.
      The significance of neuropeptide Y-immunoreactive intracardiac neurones and
      granule-containing cells and the origin of associated labelled nerve fibres in
      the heart are discussed.

PMID- 9232824
TI  - Effects of inflammation on cell proliferation in the myenteric plexus of the
      guinea-pig ileum.
AB  - This study was undertaken to investigate the occurrence and identity of dividing
      cells within the myenteric plexus of the guinea-pig ileum and to analyze the
      effects of inflammation induced by trinitrobenzene sulfonic acid. The
      incorporation of 5-bromo-2-deoxyuridine, or BrdU, into replicating DNA was used
      to label proliferative cells, and immunohistochemistry was used to assess the
      occurrence of BrdU in specific cells of the myenteric plexus. Compared to normal
      tissue, inflammation is associated with increased BrdU labelling in the crypts
      and in the substantially thickened muscle layers. In longitudinal
      muscle/myenteric plexus whole-mounts, there was a significant increase in BrdU
      labelling of the myenteric plexus after induced inflammation. No BrdU-labelled
      neurons were detected in tissue double labelled with neuron-specific antibodies.
      Fluorescein isothiocyanate/dextran-labelled macrophages were rare or absent from
      the ganglia, and none were double labelled with BrdU in the muscle layers. CD3
      immunoreactive T cells were substantially increased in the inflamed longitudinal
      muscle, but still rare or absent within the enteric ganglia. Some BrdU-labelled T
      cells were observed in the longitudinal muscle but not in the myenteric ganglia.
      Lastly, in tissues double labelled with anti-BrdU and anti-S-100, many BrdU
      containing cells within the myenteric ganglia were found to be S-100
      immunoreactive glial cells. We conclude that inflammation does not stimulate the
      appearance of new myenteric neurons but does stimulate mitosis in myenteric glia.

PMID- 9232825
TI  - Exocytosis in the antral gastrin cells of mouse, rat, and guinea pig after
      stimulation by carbamylcholine.
AB  - In order to capture the exocytotic figures of gastrin cells in the pyloric antrum
      of the stomach, we examined antral cells of the mouse, rat, and guinea pig by
      electron microscopy following stimulation with the cholinergic secretagogue
      carbamylcholine. Increased numbers of omega profiles indicative of exocytosis
      were seen in the basal or lateral cell membrane after stimulation with
      carbamylcholine. The number of exocytotic figures in stimulated gastrin cells was
      higher in the guinea pig than in the mouse and rat. Coated and non-coated omega
      profiles and coated pits in the plasma membrane were smaller than the secretory
      granules. Omega profiles with or without electron-dense contents were seen.
      Coated and non-coated vesicles were often visible near the plasma membrane of
      stimulated gastrin cells in all three species, large cytoplasmic vacuoles also
      being found in the guinea pig. In the mouse pretreated with horseradish
      peroxidase, reaction deposits were observed in the omega profiles and in
      microvesicles near the plasma membrane. These results suggest that, after
      exocytosis, membrane retrieval and endocytosis occur in the gastrin cells.

PMID- 9232826
TI  - Effects of carbachol and catecholamines on ultrastructure and intracellular
      calcium-ion dynamics of acinar and myoepithelial cells of lacrimal glands.
AB  - The current study was carried out to investigate autonomic nervous control of
      secretory functions in the lacrimal gland. To distinguish the difference between
      the responses to cholinergic and adrenergic agonists in acinar and myoepithelial
      cells in the lacrimal gland of guinea pigs, the morphological and functional
      responses to the agonists were examined by electron microscopy and by digital
      imaging analysis of the intracellular concentration of Ca2+ ([Ca2+]i) using
      fluorescent Ca2+-indicators (Fura-2/AM and Indo-1/AM). In the resting state,
      exocytosis was rare, and the [Ca2+]i in acinar and myoepithelial cells was low
      (less than 300 nM). Stimulation with carbachol (CCh) induced a rapid rise in
      [Ca2+]i reaching a peak level followed by gradual decay and an appearance of many
      exocytotic figures. Approximately 4-8 s after an initial increase of [Ca2+]i,
      myoepithelial cells commenced contraction. Noradrenaline or adrenaline induced an
      increase in [Ca2+]i and exocytosis in acinar cells, but caused no [Ca2+]i
      increase in myoepithelial cells. In a Ca2+-deficient environment, the responses
      to CCh in myoepithelial cells and those to noradrenaline in acinar cells were
      inhibited, whereas the responses to CCh in acinar cells remained unchanged.
      Isoproterenol caused no effect on [Ca2+]i dynamics, although it occasionally
      induced exocytosis. Different cellular signaling pathways may be involved in the
      responses in acinar and in myoepithelial cells to different agonists. Lacrimation
      mechanisms are redundant.

PMID- 9232827
TI  - Emergence and distribution of intimal smooth muscle cells in the postnatal rat
      aorta.
AB  - The distribution of aortic intimal smooth muscle cells in the normal rat during
      postnatal development was studied by electron microscopy and by staining with
      fluorescence-labeled phalloidin. The phenotypes of intimal and medial smooth
      muscle cells were almost identical at first; however, during development, the
      former remained synthetic, whereas the latter became contractile. Confocal laser
      scanning microscopy was utilized to observe intimal and medial cells separately.
      Intimal smooth muscle cells were rarely observed in neonatal rats, but appeared
      by 10 days of age and increased during postnatal development. A combination of
      confocal and conventional fluorescent microscopy clearly demonstrated that the
      intimal smooth muscle cells were preferentially distributed in: (1) the right
      lateral and dorsal wall of the upper thoracic aorta, (2) the left-lateral and
      ventral wall of distal two-thirds of the descending aorta, and (3) the downstream
      side of branch orifices. Intimal smooth muscle cells in group (1) were oriented
      randomly, whereas most in group (2) ran longitudinally. Intimal smooth muscle
      cells at branches in group (3) ran obliquely from the edges at the downstream
      side in an upstream direction. They tended to accumulate in regions of the aortic
      wall considered to be under high tensile stress.

PMID- 9232828
TI  - Immunohistochemical and immuno-electron-microscopic detection of interferon-gamma
      inducing factor ("interleukin-18") in mouse intestinal epithelial cells.
AB  - The novel cytokine interferon-gamma-inducing factor ("interleukin-18") is
      produced by macrophage-like cells in mice with endotoxin shock and induces the
      production of interferon-gamma by T cells in vitro. To determine the
      physiological role for mouse interferon-gamma-inducing factor, we studied its
      tissue distribution in several organs (intestine, spleen, thymus, kidney, and
      liver) in healthy mice of different ages, including fetal stages. Activity of the
      cytokine in the organ extracts of adult mice was measured by enzyme-linked
      immunosorbent assay, and the cellular distribution of interferon-gamma-inducing
      factor in organs from fetal and adult mice was determined by
      immunohistochemistry. Intestinal extracts of adult mice showed the highest
      concentrations among the organs studied. Other organ extracts of adult mice
      showed lower concentrations of the cytokine. Immunohistochemical analysis
      revealed that interferon-gamma-inducing factor was localized in the cytoplasm of
      intestinal epithelial cells from fetal and adult mice. These results show for the
      first time that intestinal epithelial cells may be the main producers of
      interferon-gamma-inducing factor under normal physiological conditions and
      suggest that its constitutive expression in intestinal epithelial cells may have
      an important role in the induction of mucosal immunity.

PMID- 9232830
TI  - Synaptic exocytosis of dense-core vesicles in blue crab (Callinectes sapidus)
      stomach muscles.
AB  - Neuromuscular terminals of a single motoneuron to four muscles (CPV7a, GM5a, CV2,
      and CV3) in the stomach of the blue crab Callinectes sapidus showed structural
      evidence for the exocytotic release of dense-core vesicles exclusively at
      synapses. The primary evidence was the appearance of dense cores in the synaptic
      cleft, accompanied by indentations of the presynaptic or postsynaptic membrane.
      In their simplest form, these consisted of an omega-shaped figure of the
      presynaptic membrane enclosing one dense core, denoting release of a single dense
      core vesicle. A larger indentation of the presynaptic membrane enclosing several
      dense cores denoted multiple release. A more complex form of multiple release was
      where the presynaptic membrane was normal, but the postsynaptic membrane
      elaborated into a sac projecting into the granular sarcoplasm and filled with
      dense cores. The postsynaptic sac in some instances was compressed into a thin,
      fingerlike extension, which lacked dense cores and, at its distal end, separated
      into small cisternae, suggesting a mechanism for membrane recycling. Profiles
      depicting single and multiple releases of dense-core vesicles were found more
      frequently at neuromuscular terminals that release relatively large amounts of
      transmitter with a single stimulus, such as CV2 and CV3, compared to those
      releasing smaller amounts, such as CPV7a and GM5a. The disparity in release sites
      among the four muscles of this single motor unit and the fact that many of the
      multiple-release figures were closely adjacent to the active zones for
      transmitter release suggest a possible modulatory role for dense-core vesicles in
      synaptic transmission. Such modulation may be long lasting, as implied by the
      postsynaptic sacs, which may permit prolonged release of the contents of their
      dense cores into the synaptic cleft. This is in keeping with the functional role
      of these stomach muscles, which is to be continuously active for long periods of
      time.

PMID- 9232829
TI  - A 54-kDa protein related to ras-guanine nucleotide release factor expressed in
      the rat exocrine pancreas.
AB  - The polymerase chain reaction was used to amplify a cDNA encoding the catalytic
      region of ras-guanine nucleotide release factor (ras-GRF1) from mouse embryonic
      stem cell mRNA. Antibodies directed against this protein were prepared and
      affinity purified. Western immunoblotting of rat tissue lysates revealed a 140
      kDa protein in brain as expected but, in addition, a strongly immunoreactive 54
      kDa protein, p54, was identified in pancreas. Expression of ras-GRF1 in pancreas
      was confirmed at the RNA level by reverse-transcriptase-coupled polymerase chain
      reaction analysis; p54 may therefore correspond to a form of ras-GRF1 or a
      closely related protein. The cellular and subcellular localization of p54 was
      investigated by enzyme-linked immunocytochemistry and immunogold electron
      microscopy. In the pancreas, p54 was expressed primarily in acinar cells, where
      it was localized along the basolateral and apicolateral plasma membranes.
      Indirect immunofluorescence microscopy of cultured acini further indicated that
      the plasma membrane localization of p54 was dependent on the maintenance of the
      acinar histotype and organized acinar structure. When primary acinar cells were
      permitted to dissipate into monolayer cultures devoid of zymogen granules, ras
      GRF1 staining became cytosolic. Our results suggest that ras-GRF1 is involved in
      the structure and function of the pancreas.

PMID- 9232831
TI  - Sub-populations of haemocytes in the adult and developing marine mussel, Mytilus
      edulis, identified by use of monoclonal antibodies.
AB  - Monoclonal antibodies specific for haemocyte sub-populations in the mussel,
      Mytilus edulis, were raised by use of separated basophilic and eosinophilic cell
      types as antigens. The antibodies could be broadly divided into 3 groups,
      reactive with sub-populations of (1) basophilic granular haemocytes, (2)
      basophilic granular and hyaline cells and (3) eosinophilic granular cells. Non
      selective antibodies staining all haemocytes were also generated. The antibodies
      bound to epitopes of differing molecular masses and, at the ultrastructural
      level, reacted principally with the granules of the haemocyte sub-populations.
      The antibodies were used to investigate haemocyte function and ontogeny and to
      test reactivity with haemocytes from mussels subject to varying degrees of
      pollution stress. Five antibodies showed reactivity with cells from the
      trochophore and veliger larvae of M. edulis, indicating that epitopes on adult
      mussel hae-mocytes are also present at much earlier stages in the life history.
      Reactivity with the larval stages was most prevalent with non-selective
      antibodies and those selective for basophilic haemocytes. When mussels from
      different sites were examined, both immunocytochemistry and ELISA showed reduced
      expression of a 140 kDa epitope in the haemocytes of mussels subject to greater
      contaminant loads. These results show that the monoclonal antibodies of the
      present study are valuable both in tracing immune-cell development and in
      detecting molecular changes under conditions of stress.

PMID- 9232832
TI  - The separation and characterisation of haemocytes from the mussel Mytilus edulis.
AB  - The separation of haemocytes from the mussel Mytilus edulis was carried out on
      continuous Percoll gradients. The haemocytes separated into three distinct
      layers, the first comprised 97% basophilic cells, the third comprised 84%
      eosinophilic cells and the middle layer was a mixture of eosinophilic and
      basophilic cells. Enzyme cytochemistry demonstrated arylsulphatase, phenol
      oxidase and peroxidase associated with the haemocytes from the third layer.
      Lectin-binding studies showed differential binding of lectins to the separated
      cells. The ultrastructural morphology demonstrated that the first layer of cells
      was composed predominantly of small agranular cells with a high nucleus to
      cytoplasm ratio. The second layer comprised a mixture of cells with the majority
      being granular cells with small granules. The third layer was almost exclusively
      composed of granular cells with small and large granules. Assays to assess the
      function of the different cells demonstrated that respiratory burst activity,
      measured as the reduction of cytochrome-c, was carried out almost entirely by the
      eosinophilic haemocytes. Similarly, levels of phagocytosis, measured as uptake of
      Escherichia coli, were much higher in the eosinophilic haemocytes. Of the
      potential mitogenic factors investigated, concanavalin A and pokeweed mitogen
      showed some evidence of inducing haemocyte proliferation.

PMID- 9232833
TI  - Local disturbance of neuronal migration in the S-100beta-retarded mutant mouse.
AB  - Homozygotes of a mouse strain with genetic polydactyly (Pdn) show disrupted
      cortical lamination and a significant decrease of S-100beta-immunoreactive
      elements in a particular area of the brain. In order to understand the abnormal
      cortical formation at the cellular level, the migration of cortical neurons and
      the development of glial cells were studied using bromodeoxyuridine (BrdU), S
      100beta, and glial fibrillary acidic protein (GFAP) immunohistochemistry.
      Homozygous mice (Pdn/Pdn) displayed a variable pattern of abnormalities.
      Irregular GFAP-positive radial glial cells and disturbance of neuronal migration
      were found in a circumscribed area of the caudo-dorsal cortex of newborn Pdn
      mouse. The number of S-100beta-positive cells was reduced in this area. The
      present results suggest that abnormal cortical lamination closely correlates with
      disturbance of neuronal migration and abnormalities of glial cells, especially a
      significant decrease of S-100beta-immunoreactive cells.

PMID- 9232834
TI  - Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by
      separation of KLH1 and KLH2.
AB  - Studies of keyhole limpet hemocyanin (KLH) normally require purification of
      functional complexes directly from living animals. An alternative procedure is
      described wherein a commercial preparation of KLH which is fully dissociated into
      its subunits (Immucothel, biosyn Arzneimittel GmbH) is reassociated in the
      presence of a high concentration of calcium and magnesium. The reassociation
      products, when observed by electron microscopy, consist of didecamers,
      multidecamers and flexible tubules of varying length. The two forms of KLH
      described previously and designated KLH1 and KLH2, are present in the
      reassociated mixture as homo-oligomers/polymers and can be separated by selective
      dissociation of the KLH2 by treatment with 1% ammonium molybdate-0.2% PEG at pH
      5.7, followed by gel filtration chromatography in this solution. In addition to
      discrete elution peaks containing didecameric KLH1 and dissociated subunits of
      KLH2, a leading peak contains a tubular/polymeric form of KLH1, not previously
      described. Under negative staining in conditions designed specifically for the
      creation of 2-dimensional crystals on mica (the negative staining-carbon film
      procedure), this tubular form of KLH1 can be transformed into a larger diameter
      multidecameric form, again not previously described for KLH1. The purified KLH2
      peak is indistinguishable from subunit material prepared from living animals.
      This, Immucothel appears to provide a standardized source of subunits suitable
      for biochemical and structural studies on the two types of KLH.

PMID- 9232835
TI  - Keyhole limpet hemocyanin (KLH), II: Characteristic reassociation properties of
      purified KLH1 and KLH2.
AB  - Subunits of the two types of keyhole limpet hemocyanin (KLH1 and KLH2), purified
      by gel filtration chromatography and preparative polyacrylamide gel
      electrophoresis from Immucothel, have been used for macromolecular reassociation
      studies. In-vitro reassociation has been achieved with a standardized system
      using a Tris-saline stabilizing buffer at pH 7.4 containing 100 mM calcium and
      magnesium chloride at 4 degrees C. The relatively slow progress of reassociation
      has been monitored and the varying oligomeric forms of KLH1 and KLH2 produced
      have been studied by transmission electron microscopy, using specimens negatively
      stained with 5% ammonium molybdate containing 1% trehalose. Specimens have also
      been prepared by platinum-carbon shadowing, following freeze-cleavage. The two
      hemocyanins reassociate to produce characteristic oligomeric and polymeric forms.
      Subunits of purified KLH1 reassociate to produce a small number of didecamers,
      short multidecamers (ca 33 nm diameter) and much larger quantity of a ca 25 nm
      diameter flexible/undulatory tubular form of varying length. These tubules
      exhibit characteristic oblique features, indicative of an 'open' helical
      structure which appears to be a loosly or incompletely annealed twisted ribbon of
      subunits. After a period of days the tubules aggregate in parallel to produce
      large paracrystalline bundles, which do not have a tendency to associate end-to
      end. Following transfer of this reassociated KLH1 to low calcium magnesium
      stabilizing buffer, the tubular bundles are unstable; they slowly break down into
      shorter lengths, fragments, subunit groups and individual subunits, which
      subsequently regenerate decamers, didecamers, and some multidecamers. Subunits of
      purified KLH2 reassociate to produce ca 25 nm diameter 'closed' tubules, which do
      not exhibit the oblique 'open' features shown by the KLH1 tubules; however, the
      ends of the these 'closed' tubules are often oblique. In addition to the tubular
      form, KLH2 reassociation also generates a somewhat small proportion of ca 33 nm
      diameter multidecamers, often containing many decamers and more than one
      'nucleating' didecamer. On transfer to low calcium magnesium stabilizing buffer
      the KLH2 tubules are remarkably stable, but the number of multidecamers slowly
      increases with time. There is a significant structural difference between the
      short KLH1 multidecamers (only detected following in-vitro reassociation) and
      those of KLH2 quite apart from their length. Study of the metal shadowed
      specimens confirmed the difference between the KLH1 and KLH2 tubular forms, with
      relatively smooth helical surface ridges and a rougher internal surface,
      indicating internalization of subunit domains that are not required for the
      construction of the tubular wall, in accord with current understanding of the
      subunit organization within the native molecules.

PMID- 9232836
TI  - Incorporating tangent refinement in the Shake-and-Bake formalism.
AB  - Shake-and-Bake is a direct-methods procedure in which phase refinement and
      Fourier refinement are alternated repetitively, unconditionally and
      automatically. The traditional Shake-and-Bake approach invoked a parameter-shift
      routine to perform phase refinement in an effort to reduce the value of minimal
      function. In this paper, parameter shift is replaced with the tangent formula as
      a means of phase refinement. This study shows that the tangent formula is more
      efficient than parameter shift for small structures when the number of refinement
      cycles and number of applications of the tangent formula per Shake-and-Bake cycle
      are chosen very carefully. For larger structures, including the 400 non-H-atom
      crambin structure, the two methods generally perform with similar efficiency.
      However, only parameter shift has successfully produced recognizable solutions
      for the difficult 317 non-H-atom structure gramicidin A.

PMID- 9232837
TI  - The pseudo-atom approach to phase determination in protein electron
      crystallography--noncentrosymmetric projections.
AB  - From an idea proposed by David Harker [Acta Cryst. (1953), 6, 731-736], the
      assembly of globular subunits in a protein can be treated as pseudo-atoms for
      normalizaTion of observed electron diffraction intensities. As demonstrated with
      published data from native or deoxycholate-treated bacteriorhodopsin, a
      multisolution approach via the Sayre-Hughes equation can then generate phase
      solutions to 6 A resolution that compare quite favorably with those determined
      earlier by phase extension. The major problem in such determinations is
      identification of the best set, especially if no lower-resolution images of the
      protein are available. (However, 15 to 10 A resolution image-derived phases could
      be used as a reference set to identify the correct solution). A viable option may
      be to compare Patterson maps, calculated from trial map peak positions, to the
      experimental autocorrelation function. Trial phase determinations for the Omp F
      porin from E. coli outer membrane, on the other hand, are somewhat less
      successful because the beta-sheet secondary structure is less well modeled by an
      array of 'globs'.

PMID- 9232838
TI  - Synthesis of biologically active polyphenolic glycosides (combretastatin and
      resveratrol series).
AB  - (E)-3-(beta-D-Glucopyranosyloxy)-4',5-dihydroxystilbene (resveratrol 3-beta-D
      glucoside, piceid), (Z)-2',3'-dihydroxy-3,4,4',5-tetramethoxystilbene
      (combretastatin A-1), (Z)-3'-hydroxy-3,4,4',5-tetramethoxystilbene
      (combretastatin A-4), (Z)-2'-hydroxy-3-4-4'-5-tetramethoxystilbene
      (combretastatin iso-A-4), alpha, beta-dihydro-2',3'-dihydro-2',3'-dihydroxy
      3,4,4',5-tetramethoxystilb ene (combretastatin B-1), the corresponding
      glucosides, and related compounds have been synthesized via Wittig reactions
      followed by glucosylation under phase-transfer catalysis. Most of the compounds
      synthesized have been tested with respect to biological activity (cytostatic,
      cytotoxic, antimitotic, neurotoxic, antiplatelet, aggregation activity).

PMID- 9232839
TI  - Structure of the O18 antigen from Acinetobacter baumannii.
AB  - The polymeric O antigen was obtained from lipopolysaccharide extracted from
      isolated, defatted cell walls of the reference strain for Acinetobacter baumannii
      serogroup O18. Monosaccharide analyses and NMR spectra established that the
      polymer had a regular structure with a repeating unit based on residues of D
      galactose (2), N-acetyl-D-galactosamine (1), and N-acetyl-D-mannosamine (1).
      Further interpretation of the NMR spectra, combined with the results of
      methylation analysis and a Smith degradation, showed that the repeating unit had
      the following structure. beta-D-ManpNAc-(1-->4)-alpha-D-Galp 1 decreases 4 -->3)
      beta-D-GalpNAc-(1-->3)-beta-D-Galp-(1-->.

PMID- 9232840
TI  - Structural studies of the extracellular polysaccharide from Butyrivibrio
      fibrisolvens strain CF3.
AB  - The structure of the Butyrivibrio fibrisolvens strain CF3 capsular polysaccharide
      has been investigated mainly by sugar and methylation analyses, Smith
      degradation, NMR spectroscopy, and mass spectrometry. The results indicate that
      the polysaccharide is composed of pentasaccharide repeating units having the
      following structure: -->4)-beta-L-Altp-(1-->4)-beta-D-Glcp-(1-->3)-4-O-[(R)-1
      carboxyet hyl]-beta- D-Glcp-(1-->4)-6-O-[(R)-1-carboxyethyl]-alpha-D-Galp-(1--> 2
      increases 1 beta-D-Glcp.

PMID- 9232842
TI  - A method to search for similar protein local structures at ligand binding sites
      and its application to adenine recognition.
AB  - We have developed a method of searching for similar spatial arrangements of atoms
      around a given chemical moiety in proteins that bind a common ligand. The first
      step in this method is to consider a set of atoms that closely surround a given
      chemical moiety. Then, to compare the spatial arrangements of such surrounding
      atoms in different proteins, they are translated and rotated so that the chemical
      moieties are superposed on each other. Spatial arrangements of surrounding atoms
      in a pair of proteins are judged to be similar, when there are many corresponding
      atoms occupying similar spatial positions. Because the method focuses on the
      arrangements of surrounding atoms, it can detect structural similarities of
      binding sites in proteins that are dissimilar in their amino acid sequences or in
      their chain folds. We have applied this method to identify modes of nucleotide
      base recognition by proteins. An all-against-all comparison of the arrangements
      of atoms surrounding adenine moieties revealed an unexpected structural
      similarity between protein kinases, cAMP-dependent protein kinase (cAPK), and
      casein kinase-1 (CK1), and D-Ala:D-Ala ligase (DD-ligase) at their adenine
      binding sites, despite a lack of similarity in their chain folds. The similar
      local structure consists of a four-residue segment and three sequentially
      separated residues. In particular the four-residue segments of these enzymes were
      found to have nearly identical conformations in their backbone parts, which are
      involved in the recognition of adenine. This common local structure was also
      found in substrate-free three-dimensional structures of other proteins that are
      similar to DD-ligase in the chain fold and of other protein kinases. As the
      proteins with different folds were found to share a common local structure, these
      proteins seem to constitute a remarkable example of convergent evolution for the
      same recognition mechanism.

PMID- 9232841
TI  - The structure of the capsular polysaccharide from a swarming strain of pathogenic
      Proteus vulgaris.
AB  - The structure was determined for the capsular polysaccharide (CPS) isolated from
      a swarming strain of Proteus vulgaris, CP2-96, which was obtained from the spleen
      of an infected mouse. The CPS was extracted from the cell pellet by hot water,
      precipitated with ethanol, and further purified by gel-permeation chromatography.
      The structure was established by glycosyl composition and linkage analyses, and
      by NMR spectroscopy. The sequence of the glycosyl residues was determined by a
      NOESY experiment. The CPS is composed of a tetrasaccharide repeating unit with
      the following structure: OAc [symbol: see text] 4 -->4)-beta-D-Glcp-(1-->3)-beta
      D-GalpNAc-(1-->2)-alpha-D-Glcp-(1-->4)-al pha- D-GlcpA-(1-->.

PMID- 9232843
TI  - Conformational analysis of galanin using end to end distance distribution
      observed by Forster resonance energy transfer.
AB  - The structural dynamics of the flexible neuropeptide galanin in solution were
      studied by Forster resonance energy transfer measurements at different
      temperatures by time-resolved fluorescence spectroscopy to determine its
      conformational heterogeneity. Endogenous tryptophan at position 2 acted as the
      fluorescent donor and the non fluorescent acceptor dinitrophenyl or the
      fluorescent acceptor dansyl were selectively attached to lysine 25 in porcine
      galanin. The coexistence of different structures of the neuropeptide galanin in
      trifluoroethanol solution was revealed by the model independent analysis of the
      distribution of relaxation times from the time-resolved resonance energy transfer
      data. Multiple conformational states are reflected by distinct end-to-end
      distance populations. The conformations differ in mean donor-acceptor distance by
      about 15, and are consistent with the extended and folded backbone conformations
      of two alpha-helical regions separated by a flexible hinge. The effect that the
      labelling of galanin has on binding to the receptor was also evaluated. DNP
      galanin showed the same high affinity to galanin receptors as unlabelled galanin,
      whereas DNS-galanin had significantly reduced affinity.

PMID- 9232844
TI  - Crystallization of monoacylated proteins: influence of acyl chain length.
AB  - The crystallization of monoacylated proteins has been investigated using a model
      system. Acylated derivatives of bovine pancreatic ribonuclease A, differing in
      their acyl chain lengths (10 to 16 carbon atoms), have been prepared using
      reverse micelles as microreactors. With one fatty acid moiety per polypeptide
      chain, covalently attached to the NH2 terminus of the protein, all the modified
      proteins have similar enzymatic activity and hydrodynamic radius as the native
      protein. Only the caprylated derivative can give crystals which diffract to high
      resolution. The resolved structure indicates that: (i) the protein folding is not
      modified by the chemical modification, (ii) the capryl moiety is not buried
      within the molecule but available for external interactions. Dynamic light
      scattering experiments on concentrated solutions show that the protein-protein
      interactions are dependent on acyl chain length. Proteins with the longest
      attached chains (14 and 16 carbon atoms) tend to self-associate through acyl
      group interactions.

PMID- 9232845
TI  - Effect of blood storage on erythrocyte/wall interactions: implications for
      surface charge and rigidity.
AB  - In this report, we study, under flow conditions, the interactions of stored
      erythrocytes with an artificial surface: a microelectrode whose charge density
      ranges from -15 to +27 microC/cm2. Interactions consist of red cells slowly
      circulating on the microelectrode and exerting a real contact with the electrode.
      Interaction is detected and measured by transient fluctuations of the electrolyte
      resistance obtained by impedance measurement of the microelectrode. Effects of
      aging induced by storage of whole blood at 4 degrees C show that the surface
      charge of erythrocytes rapidly decreases when blood is stored for more than 6
      days under our experimental conditions. In comparison with trypsin-treated
      erythrocytes, an eight day storage induces a 60% decrease in the surface charge
      of red cells. After two weeks of storage, red cells are no longer negatively
      charged, presumably because of removal of sialic acid. Cells rigidity is
      significant after 6 days of storage and influences the electrical contact.
      Membrane rigidity increase could arise from the surface charge decrease. Finally
      the surface charge decrease could be importance in the use of stored blood.

PMID- 9232846
TI  - Fluorescence study of neurohypophyseal hormones and their analogues. Distance
      distributions in a series of arginine-vasopressin analogues.
AB  - Analogues of arginine-vasopressin (AVP) in which substitution of the proline
      residue in position 7 (by either sarcosine or N-methylalanine) combined with
      replacement of the cysteine residue in position 1 were the subject of a
      fluorescence and molecular mechanics study. We obtained two groups of analogues:
      selective antidiuretic agonists (cysteine or beta-mercaptopropionic acid in
      position 1) and pressor and uterotonic antagonists (deaminopenicillamine or beta
      mercapto-beta, beta-cyclopentamethylenepropionic acid in position 1). Using
      frequency-domain measurements of fluorescence resonance energy transfer (FRET) we
      estimated the distance distribution between the phenolic ring of Tyr2 and the
      disulphide bridge Cys1-Cys6. We also analyzed acrylamide quenching of tyrosyl
      fluorescence to determine the exposure of the tyrosyl ring to the solvent.
      Results from fluorescence experiments were compared with those from Monte Carlo
      simulation (ECEPP/3 force-field).

PMID- 9232847
TI  - High pressure effects on the colloidal calcium phosphate and the structural
      integrity of micellar casein milk. Part 1. High pressure dissolution of colloidal
      calcium phosphate in heated milk systems.
AB  - Results of this study confirm that high temperature (118 degrees C/15 min) and
      high pressure (400 MPa/5 min) processing of skim milk, skim milk ultrafiltration
      and ultracentrifugation fractions, and model milk salt solutions cause dramatic
      shifts in their colloidal and soluble Ca phosphate equilibrium that affect their
      pH, dissolved Ca content, turbidity, and casein micelle microstructure. The
      relations between high temperature and high pressure processing-induced changes
      in the colloidal and soluble Ca phosphate equilibrium were evaluated in raw,
      pasteurized, and high temperature treated skim milk, ultrafiltration retentate
      and permeate of pasteurized skim milk, clear ultracentrifugation infranatant of
      pasteurized skim milk, and synthetic milk ultrafiltrates with and without lactose
      or Ca. The magnitude of the pH and dissolved Ca shifts caused by high temperature
      and high pressure processing was a function of casein micelle concentration.
      Ultrafiltration permeate exhibited the most drastic shits in pH and dissolved Ca
      contents due to high temperature and high pressure processing. Although high
      temperature processing reduced the pH of ultrafiltration permeate from 6.59 to
      6.03 and the dissolved Ca from 100% to 58%, high pressure processing reversed
      both of these changes. These changes in high temperature and high pressure
      processed milk, milk fractions, and model milk salt solutions were related to
      microstructural changes in the casein micelles as revealed by electron
      microscopy.

PMID- 9232848
TI  - Mold spectrum of four cereal brands of the German crop 1995.
AB  - The concentration of extracellular polysaccharides (EPS) of 80 cereal grain
      samples of the German harvest 1995 was investigated. In addition to this, the
      total as well as the inherent mycoflora of two winter wheat and two winter rye
      brands which showed the highest EPS-concentration was detected on maltsalt agar
      (NaCl 5%). Surface disinfection with 1% NaOCl for the determination of the
      internal mycoflora caused a significant reduction in number and kind of fungi.
      However, the mycoflora of all samples was dominated by fungi of the genera
      Alternaria spp. and Cladosporium spp., Aureobasidium pullulans, Fusarium spp. and
      Epicoccum purpurascens (in decreasing order) occurred to a minor extent. A
      possible contamination of the cereal grains with mycotoxins of Alternaria and
      Cladosporium is discussed.

PMID- 9232849
TI  - Glycoalkaloid content of potatoes sold in Czechia.
AB  - Glycoalkaloid levels in different cultivars collected from three regions were
      monitored during two years. With the exception of Karin, one of the most widely
      grown cultivar in the Czech Republic, none of the cultivars used for human
      consumption exceeded the levels considered safe. The average of total
      glycoalkaloids content for tested cultivars ranged from 31 to 166 mg/kg fresh
      weight. There were no significant differences between glycoalkaloid levels in
      tubers from different regions. Attention was paid to the adequate sampling
      procedure.

PMID- 9232850
TI  - Influence of white light, near-UV irradiation and other environmental conditions
      on production of aflatoxin B1 by Aspergillus flavus and ochratoxin A by
      Aspergillus ochraceus.
AB  - The effects of illumination, near-ultraviolet, incubation temperature pH and some
      minor elements on the growth rate and production of aflatoxin B1 by A. flavus and
      ochratoxin A by A. ochraceus were investigated. Aflatoxin B1 and ochratoxin A
      production was considerably higher in the light than in the dark. The greatest
      aflatoxin B1 and ochratoxin A production was occurred after 11 days of
      fermentation with light- and dark-grown cultures at 25 degrees C. The mycelial
      dry weight was also greater in the light than in the dark for both A. flavus and
      A. ochraceus. Exposure of conidia to near-UV irradiation increased mycelial dry
      weight and mycotoxins by both fungi more than white light. The greatest aflatoxin
      B1 and ochratoxin A was at 25 degrees C with UV-grown culture (24 h exposure)
      producing a mean of 400 and 260 micrograms/50 ml of medium, respectively. The
      maximum aflatoxin B1 and ochratoxin A yield was obtained at pH 5.5 and with
      increasing the initial pH to near neutrality, both mycotoxins yield decreased.
      Iron, copper and zinc were observed to stimulate aflatoxin B1 and ochratoxin A
      production and enhanced the growth rate of both A. flavus and A. ochraceus.

PMID- 9232851
TI  - Microbiological, nutritional and sensory aspects of stored amaranth biscuits and
      amaranth crackers.
AB  - The object of this work was to present some results from the evaluation of
      microbiological (total bacterial count, coliform bacteria, aerobic sporogenic
      bacteria, yeasts and moulds), nutritional (lysine) and sensory (shape, surface,
      colour, consistency, odour, taste, the profiling of tastiness) quality and of the
      a(w) values of amaranth biscuits and crackers during the four-month storage
      (January-April, 1996 every 30th day) in laboratory conditions (20 +/- 2 degrees C
      and RH = 62 +/- 1%). From the aspect of consumers the chosen parameters of
      quality permitted the storage stability of the indicated non-traditional products
      to be estimated and on the basis of the favourable evaluation recommended for the
      rational nutrition.

PMID- 9232852
TI  - Application potential for some sugar substitutes in some low energy and diabetic
      foods.
AB  - Preparation of acceptable low energy fiber enriched and diabetic jams, cakes and
      biscuits using different formulas of sucrose substitutes with the partial
      replacement of wheat flour with bran as a source of dietary fibre, was studied.
      Special care was paid to evaluate the nutritional plus keeping qualities and the
      potential effect of the most acceptable formulae from each food stuffs group on
      the blood glucose level in lean and obese diabetes mellitus patients. It was
      technologically possible to prepare acceptable, high nutritional diabetic and low
      energy apricot, guava and strawberry jams and jellies by combinations of
      sweeteners using xylitol (i.e. xylitol-sorbitol-aspartame and xylitol-fructose).
      The attainment of a suitable texture may be more difficult in xylitol and
      sorbitol jams, therefore 0.2 g CaCl2. 2H2O was added. Storage of these jams at 4
      degrees C improved their keeping quality significantly (p < 0.05), where the
      microbial load was less than 20 cells per gram and the products were free from
      molds and yeasts. Also, high nutritional and acceptable cakes and biscuits for
      low energy supply and for diabetic subjects can be sweetened with low level of
      aspartame in combination with fructose, sorbitol and xylitol. Consumption of such
      low energic and diabetic food items reduces significantly (p < 0.05) the plasma
      glucose level in lean and obese diabetics. Addition of wheat bran in bakery
      products not only reduced both energy value of these foods and blood glucose, but
      it also improved peripheral insulin activity by its system modification.

PMID- 9232853
TI  - Non-invasive measurements of breast tissue optical properties using frequency
      domain photon migration.
AB  - A multiwavelength, high bandwidth (1 GHz) frequency-domain photon migration
      (FDPM) instrument has been developed for quantitative, non-invasive measurements
      of tissue optical and physiological properties. The instrument produces 300 kHz
      to 1 GHz photon density waves (PDWs) in optically turbid media using a network
      analyser, an avalanche photodiode detector and four amplitude-modulated diode
      lasers (674 nm, 811 nm, 849 nm, and 956 nm). The frequency of PDW phase and
      amplitude is measured and compared to analytically derived model functions in
      order to calculate absorption, mu a, and reduced scattering, mu s, parameters.
      The wavelength-dependence of absorption is used to determine tissue haemoglobin
      concentration (total, oxy- and deoxy- forms), oxygen saturation and water
      concentration. We present preliminary results of non-invasive FDPM measurements
      obtained from normal and tumour-containing human breast tissue. Our data clearly
      demonstrate that physiological changes caused by the presence of small (about 1
      cm diameter) palpable lesions can be detected using a handheld FDPM probe.

PMID- 9232854
TI  - Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared
      spectroscopy.
AB  - Cytochrome oxidase is the terminal electron acceptor of the mitochondrial
      respiratory chain. It is responsible for the vast majority of oxygen consumption
      in the body and essential for the efficient generation of cellular ATP. The
      enzyme contains four redox active metal centres; one of these, the binuclear CuA
      centre, has a strong absorbance in the near-infrared that enables it to be
      detectable in vivo by near-infrared spectroscopy. However, the fact that the
      concentration of this centre is less than 10% of that of haemoglobin means that
      its detection is not a trivial matter. Unlike the case with deoxyhaemoglobin and
      oxyhaemoglobin, concentration changes of the total cytochrome oxidase protein
      occur very slowly (over days) and are therefore not easily detectable by near
      infrared spectroscopy. However, the copper centre rapidly accepts and donates an
      electron, and can thus change its redox state quickly; this redox change is
      detectable by near-infrared spectroscopy. Many factors can affect the CuA redox
      state in vivo (Cooper et al. 1994), but most significant is likely to be the
      molecular oxygen concentration (at low oxygen tensions, electrons build up on CuA
      as reduction of oxygen by the enzyme starts to limit the steady-state rate of
      electron transfer). The factors underlying haemoglobin oxygenation, deoxygenation
      and blood volume changes are, in general, well understood by the clinicians and
      physiologists who perform near-infrared spectroscopy measurements. In contrast,
      the factors that control the steady-state redox level of CuA in cytochrome
      oxidase are still a matter of active debate, even amongst biochemists studying
      the isolated enzyme and mitochondria. Coupled with the difficulties of accurate
      in vivo measurements it is perhaps not surprising that the field of cytochrome
      oxidase near-infrared spectroscopy has a somewhat chequered past. Too often
      papers have been written with insufficient information to enable the measurements
      to be repeated and few attempts have been made to test the algorithms in vivo. In
      recent years a number of research groups and commercial spectrometer
      manufacturers have made a concerted attempt to not only say how they are
      attempting to measure cytochrome oxidase by near-infrared spectroscopy but also
      to demonstrate that they are really doing so. We applaud these attempts, which in
      general fall into three areas: first, modelling of data can be performed to
      determine what problems are likely to derail cytochrome oxidase detection
      algorithms (Matcher et al. 1995); secondly haemoglobin concentration changes can
      be made by haemodilution (using saline or artificial blood substitutes) in
      animals (Tamura 1993) or patients (Skov & Greisen 1994); and thirdly, the
      cytochrome oxidase redox state can be fixed by the use of mitochondrial
      inhibitors and then attempts make to cause spurious cytochrome changes by
      dramatically varying haemoglobin oxygenation, haemoglobin concentration and light
      scattering (Cooper et al. 1997). We have previously written reviews covering the
      difficulties of measuring the cytochrome near-infrared spectroscopy signal in
      vivo (Cooper et al. 1997) and the factors affecting the oxidation state of
      cytochrome oxidase CuA (Cooper et al. 1994). In this article we would like to
      strike a somewhat more optimistic note--we will stress the usefulness this
      measurement may have in the clinical environment, as well as describing
      conditions under which we can have confidence that we are measuring real changes
      in the CuA redox state.

PMID- 9232855
TI  - Oxidative metabolism in muscle.
AB  - Oxidative metabolism is the dominant source of energy for skeletal muscle. Near
      infrared spectroscopy allows the non-invasive measurement of local oxygenation,
      blood flow and oxygen consumption. Although several muscle studies have been made
      using various near-infrared optical techniques, it is still difficult to
      interpret the local muscle metabolism properly. The main findings of near
      infrared spectroscopy muscle studies in human physiology and clinical medicine
      are summarized. The advantages and problems of near-infrared spectroscopy
      measurements, in resting and exercising skeletal muscles studies, are discussed
      through some representative examples.

PMID- 9232857
TI  - Cerebral oxygenation and haemodynamics in the foetus and newborn infant.
AB  - Quantitative techniques have been derived for the measurement of global cerebral
      blood flow, cerebral blood volume, its response to changing arterial carbon
      dioxide tension and mixed cerebral venous saturation in the human newborn
      undergoing intensive care. Normal ranges have been established and significant
      disturbances of cerebral oxygenation and perfusion have been demonstrated in a
      variety of pathological conditions. Recently, absolute cerebral deoxyhaemoglobin
      concentration has been obtained in the newborn using second differential
      spectroscopy. When combined with the measurement of total cerebral haemoglobin
      concentration, the mean saturation of cerebral blood (SmcO2) may be obtained,
      allowing global cerebral oxygenation to be determined continuously in the
      intensive care unit. Marked changes in the concentrations of cerebral oxy- and
      deoxyhaemoglobin have been observed in foetuses undergoing labour. Measurements
      of SmcO2 from the foetal brain prior to delivery have shown the expected close
      correlation with acid-base status at birth. Although movement artefact remains a
      theoretical risk during uterine contractions, preliminary measurements of optical
      path length by intensity-modulated spectroscopy have demonstrated only small
      fluctuations. In future the clinical application of time, phase and spatially
      resolved spectroscopy is likely to improve both the quantitative accuracy and the
      regional specificity of physiological measurements in the foetal and neonatal
      brain.

PMID- 9232856
TI  - Measurements of tissue viability in transplantation.
AB  - Near-infrared spectroscopy has primarily been used in monitoring changes in
      cerebral haemoglobin oxygenation and haemodynamics. However its use as a method
      for the assessment of tissue viability following transplantation has recently
      been explored experimentally in our laboratory. The ability to measure changes in
      oxygenation and perfusion during harvesting and following transplantation of
      organs or transfer of free and pedicled flaps potentially important in
      reconstructive surgery. We have found that near-infrared spectroscopy is
      extremely useful in detecting vaso-occlusive events and can accurately and
      reliably distinguish between arterial, venous or total occlusions. Venous
      congestion indicated by raised levels of deoxygenated haemoglobin with a
      concomitant increase in blood volume and the presence and magnitude of reactive
      hyperaemia are both easily recognizable features by near-infrared spectroscopy.
      We have shown that near-infrared spectroscopy measurements of venous congestion
      in kidneys (and other tissues) following prolonged storage correlate with
      medullary vascular congestion confirmed by angiographical and histological
      analysis of intrarenal perfusion. Clinically we have shown that flap perfusion
      can be improved by altering fluid replacement regimes and the addition of
      ionotropes. Cerebral near-infrared spectroscopy measurements in a liver
      transplant model showed statistically significant differences within minutes
      after the anhepatic phase in cerebral perfusion and oxygenation, between animals
      transplanted with ischaemically damaged livers compared to those isografted with
      minimally stored livers. Similarly we have found that near-infrared spectroscopy
      can be used as a monitor to assess the adequacy of fluid or blood replacement in
      haemorrhagic and hypovolaemic models. We believe that near-infrared spectroscopy
      provides a sensitive and reliable postoperative method for the assessment of
      tissue viability following the transfer of free and pedicled flaps and organs.

PMID- 9232858
TI  - Use of near-infrared spectroscopy in the adult.
AB  - Adult near-infrared spectroscopy is a potential method for observing changes in
      cerebral oxygenation non-invasively. Access of light to the adult brain requires
      requires penetration through extracranial tissues; hence the detection of changes
      in cerebral chromophore concentration can only be achieved by using near-infrared
      spectroscopy in the reflectance-mode thereby adding variables which are difficult
      to control. These include the effects of variable anatomy, different intra-optode
      distances and the presence of an extra- to intracranial collateral blood supply.
      Although movements of oxygenated haemoglobin concentration following specific
      cerebral stimuli can be demonstrated, the challenge of separating changes which
      occur within the extracranial compartment from those occurring in the
      intracranial compartments remains. Our experience with near-infrared spectroscopy
      in the three adult clinical scenarios of carotid endarterectomy, head injury and
      carbon dioxide stress testing will be presented. The influence of extracranial
      contamination is demonstrated, as are the methods we have developed to help
      control for extracranial contamination. Provisional experience with spatially
      resolved spectroscopy technology will also be presented.

PMID- 9232859
TI  - Optical investigations of physiology: a study of intrinsic and extrinsic
      biomedical contrast.
AB  - The utility and performance of optical studies of tissue depends upon the
      contrast and the changes of contrast in health and disease and in functional
      activity. The contrast is determined both by the optical properties of extrinsic
      chromophores and scatterers but especially upon the changes evoked by
      physiological activity and pathological states. Here, we have focused upon
      absorption changes of the intrinsic probe, blood absorbance changes due to
      cortical hypoxia and to haematomas, giving, for particular conditions, absorbance
      changes of 0.15 and over 0.4 delta OD, respectively. Functional activity may give
      changes of blood volume of over 0.05 delta OD with some variability due to
      individual responses that is best expressed as histogram displays of the
      distribution of response among a significant population. Responses have been
      observed in prefrontal parietal and occipital functions (242 tests). Extrinsic
      probes afford signals dependent upon the dose tolerance of the subject and can
      readily equal or exceed the blood volume and oxygenation signals, and currently
      afford vascular volume and flow indications. However, contrast agents for the
      functional activity of cellular function are ultimately to be expected. Finally,
      light-scattering changes afford osmolyte-related responses and are here shown to
      indicate a larger signal attributed to cortical depolarization and K+ release in
      hypoxia/ischaemia. Thus, the optical method affords imaging of manifold contrasts
      that greatly enhance its specificity and sensitivity for diagnostic procedures.

PMID- 9232860
TI  - Image reconstruction in optical tomography.
AB  - Optical tomography is a new medical imaging modality that is at the threshold of
      realization. A large amount of clinical work has shown the very real benefits
      that such a method could provide. At the same time a considerable effort has been
      put into theoretical studies of its probable success. At present there exist gaps
      between these two realms. In this paper we review some general approaches to
      inverse problems to set the context for optical tomography, defining both the
      terms forward problem and inverse problem. An essential requirement is to treat
      the problem in a nonlinear fashion, by using an iterative method. This in turn
      requires a convenient method of evaluating the forward problem, and its
      derivatives and variance. Photon transport models are described for obtaining
      analytical and numerical solutions for the most commonly used ones are reviewed.
      The inverse problem is approached by classical gradient-based solution methods.
      In order to develop practical implementations of these methods, we discuss the
      important topic of photon measurement density functions, which represent the
      derivative of the forward problem. We show some results that represent the most
      complex and realistic simulations of optical tomography yet developed. We
      suggest, in particular, that both time-resolved, and intensity-modulated systems
      can reconstruct variations in both optical absorption and scattering, but that
      unmodulated, non-time-resolved systems are prone to severe artefact. We believe
      that optical tomography reconstruction methods can now be reliably applied to a
      wide variety of real clinical data. The expected resolution of the method is
      poor, meaning that it is unlikely that the type of high-resolution images seen in
      computed tomography or medical resonance imaging can ever be obtained.
      Nevertheless we strongly expect the functional nature of these images to have a
      high degree of clinical significance.

PMID- 9232861
TI  - Measurements of scattering and absorption changes in muscle and brain.
AB  - Non-invasive techniques for the study of human brain function based on changes of
      the haemoglobin content or on changes of haemoglobin saturation have recently
      been proposed. Among the new methods, near-infrared transmission measurements may
      have significant advantages and complement well-established methods such as
      functional magnetic resonance imaging and positron emission tomography. Near
      infrared measurements can be very fast, comparable in speed to
      electrophysiological measurements, bur are better localized. We will present the
      demonstration of measurements of millisecond signals due to brain activity in
      humans following stimulation of the visual cortex. However, major unresolved
      questions remain about the origin of the signals observed. Optical measurements
      on exposed cortex in animals show that both the absorption and the scattering
      coefficient are affected by neural activity. Model calculations show that the
      signals we detected may originate from rapid changes of the scattering
      coefficient in a region about 1 to 2 cm below the scalp. We discuss our
      measurement protocol, which is based on a frequency-domain instrument, and the
      algorithm to separate the absorption from the scattering contribution in the
      overall response. Our method produces excellent separation between scattering and
      absorption in relatively homogeneous masses such as large muscles. The
      extrapolation of our measurement protocol to a complex structure such as the
      human head is critically evaluated.

PMID- 9232862
TI  - Localized near-infrared spectroscopy and functional optical imaging of brain
      activity.
AB  - Changes in cerebral blood flow (CBF) and cerebral metabolic rates (CMRO2) have
      been used as indices for changes in neuronal activity. Near-infrared spectroscopy
      (NIRS) can also measure cerebral haemodynamics and metabolic changes, enabling
      the possible use of multichannel recording of NIRS for functional optical imaging
      of human brain activity. Spatio-temporal variations of brain regions were
      demonstrated during various mental tasks. Non-synchronous behaviour of cerebral
      haemodynamics during the neuronal activation was observed. Gender- and handedness
      dependent lateralization of the function between right and left hemispheres was
      demonstrated by simultaneous measurement using two NIR instruments during the
      mirror-drawing task. A lack of interhemispheric integration was observed with
      schizophrenic patients. These observations suggest an application for NIRS in
      psychiatric disease management, as an addition to clinical monitoring at the
      bedside. A time resolved 64-channel optical imaging system was constructed. This
      consisted of three picosecond laser diodes and 64 channels of TAC and CFD
      systems. Image reconstruction for phantom model systems was performed. Time
      resolved quantitative optical imaging will become real in the very near future.

PMID- 9232863
TI  - Cerebral haemoglobin oxygenation during sustained visual stimulation--a near
      infrared spectroscopy study.
AB  - Using near-infrared spectroscopy, we investigated the time-course of the
      concentrations of oxygenated haemoglobin, [oxy-Hb], and deoxygenated haemoglobin
      [deoxy-Hb], in the occipital cortex of healthy human adults during standard
      sustained visual stimulation. Within a few seconds after stimulation (by coloured
      dodecahedron), we observed a decrease in [deoxy-Hb], peaking after 13 s ('initial
      undershoot'). In the subsequent 1-2 min, in seven out of ten subjects, [deoxy-Hb]
      gradually returned to a plateau closer to the baseline level. After cessation of
      stimulation, there was a 'post-stimulus overshoot' in [deoxy-Hb]. There was a
      statistically significant correlation between the size of the 'initial
      undershoot' and the post-stimulus overshoot'. The concentration of oxyhaemoglobin
      increased upon functional activation. However, in the mean across all subjects
      there was no 'initial overshoot'. After approximately 19 s it reached a plateau
      and remained constantly elevated throughout the activation period. After
      cessation of activation there was a 'post-stimulus undershoot' of oxyhaemoglobin.
      It is important to consider the time-course of haemoglobin oxygenation when
      interpreting functional activation data, especially those data obtained with
      oxygenation-sensitive methods, such as BOLD-contrast fMRI.

PMID- 9232864
TI  - The influence of demographic factors on phase-modulated spectroscopy in adults.
AB  - The increased complexity of phase-modulated spectroscopy (PMS) compared with
      incoherent light techniques of near-infrared spectroscopy is justified if
      measurement of path length is necessary. In order to assess the variability of
      optical transmission in the head of adults, 96 subjects of varying age, gender
      and skin pigmentation were studied using an experimental three-wavelength time
      shared PMS device. Optical path length was measured at each wavelength, and
      saturation and haemoglobin-free path length were calculated. Path length varied
      linearly with the separation of the optical probes, but gender, age or skin
      pigmentation were not associated with differences in path length. Haemoglobin
      saturation averaged 68% and varied with age in a non-uniform fashion. Haemoglobin
      free path length differed between genders, being 8% longer in women than in men.
      Measurements could not be performed at 5 cm due to optical attenuation in 36% of
      subjects. These subjects were more often young, but they were not otherwise
      distinguished by gender or pigmentation differences. Subjects in whom
      measurements could be obtained at 5 cm had longer haemoglobin-free path lengths
      than did subjects in whom optical attenuation prevented these measurements. These
      data confirm the occurrence of significant differences in optical transmission in
      adults and support the use of PMS techniques that measure path length.

PMID- 9232865
TI  - Imaging brain structure and function, infection and gene expression in the body
      using light.
AB  - Light can be used to probe the function and structure of human tissues. We have
      been exploring two distinct methods: (i) externally emitting light into tissue
      and measuring the transmitted light to characterize a region through which the
      light has passed, and (ii) internally generating light within tissue and using
      the radiated light as a quantitative homing beacon. The emitted-light approach
      falls within the domain of spectroscopy, and has allowed for imaging of
      intracranial haemorrhage in newborns and of brain functions in adults. The
      generated-light approach is conceptually parallel to positron emission tomography
      (PET) or nuclear medicine scanning, and has allowed for real-time, non-invasive
      monitoring and imaging of infection and gene expression in vivo using low-light
      cameras and ordinary lenses. In this paper, we discuss recent results and
      speculate on the applications of such techniques.

PMID- 9232866
TI  - Genetic analysis of abscisic acid signal transduction.

PMID- 9232867
TI  - Identification and characterization of a fruit-specific, thaumatin-like protein
      that accumulates at very high levels in conjunction with the onset of sugar
      accumulation and berry softening in grapes.
AB  - The protein composition of the grape (Vitis vinifera cv Muscat of Alexandria)
      berry was examined from flowering to ripeness by gel electrophoresis. A protein
      with an apparent molecular mass of 24 kD, which was one of the most abundant
      proteins in extracts of mature berries, was purified and identified by amino acid
      sequence to be a thaumatin-like protein. Combined cDNA sequence analysis and
      electrospray mass spectrometry revealed that this protein, VVTL1 (for V. vinifera
      thaumatin-like protein 1), is synthesized with a transient signal peptide as seen
      for apoplastic preproteins. Apart from the removal of the targeting signal and
      the formation of eight disulfide bonds, VVTL1 undergoes no other
      posttranslational modification. Southern, northern, and western analyses revealed
      that VVTL1 is found in the berry only and is encoded by a single gene that is
      expressed in conjunction with the onset of sugar accumulation and softening. The
      exact role of VVTL1 is unknown, but the timing of its accumulation correlates
      with the inability of the fungal pathogen powdery mildew (Uncinula necator) to
      initiate new infections of the berry. Western analysis revealed that the presence
      of thaumatin-like proteins in ripening fruit might be a widespread phenomenon.

PMID- 9232868
TI  - A class IV chitinase is highly expressed in grape berries during ripening.
AB  - Chitinase activity increased markedly at the onset of ripening in grape (Vitis
      vinifera L.) berries and continued to increase throughout the sugar accumulation
      phase of berry development. In contrast, beta-1,3-glucanase activity was not
      detected in grape berries at any stage of development. Two closely related
      chitinase cDNAs (VvChi4A and VvChi4B) were cloned from grapes. Sequence and
      Southern analysis indicate that these two clones may represent alleles of the
      same gene. The predicted proteins are acidic and have a signal peptide followed
      by a cysteine-rich, chitin-binding domain and a catalytic region. An analysis of
      their sequences indicates that they are class IV chitinase. The deduced protein
      sequence of VvChi4A has a high level of identity with the 32- and 28-kD
      chitinases present as haze proteins in wine. Expression of VvChi4 was high in
      berries and low in flowers but was not detected in leaves, roots, or seeds. No
      expression was detected in berries 2 to 8 weeks postflowering, but expression was
      high 12 to 16 weeks postflowering, which coincided with sugar accumulation and an
      increase in chitinase activity. Constitutive expression of VvChi4 appears to be
      fruit-specific and induced at high levels in grapes during ripening.

PMID- 9232869
TI  - Genetic and developmental control of nuclear accumulation of COP1, a repressor of
      photomorphogenesis in Arabidopsis.
AB  - Using a beta-glucuronidase (GUS) reporter-COP1 fusion transgene, it was shown
      previously that Arabidopsis COP1 acts within the nucleus as a repressor of
      seedling photomorphogenic development and that high inactivation of COP1 was
      accompanied by a reduction of COP1 nuclear abundance (A.G. von Arnim, X.-W. Deng
      [1994] Cell 79: 1035-1045). Here we report that the GUS-COP1 fusion transgene can
      completely rescue the defect of cop1 mutations and thus is fully functional
      during seedling development. The kinetics of GUS-COP1 relocalization in a cop1
      null mutant background during dark/light transitions imply that the regulation of
      the functional nuclear COP1 level plays a role in stably maintaining a committed
      seedling's developmental fate rather than in causing such a commitment. Analysis
      of GUS-COP1 cellular localization in mutant hypocotyls of all pleiotropic
      COP/DET/FUS loci revealed that nuclear localization of GUS-COP1 was diminished
      under both dark and light conditions in all mutants tested, whereas nuclear
      localization was not affected in the less pleiotropic cop4 mutant. Using both the
      brassinosteroid-deficient mutant det2 and brassinosteroid treatment of wild-type
      seedlings, we have demonstrated that brassinosteroid does not control the
      hypocotyl cell elongation through regulation nuclear localization of COP1. The
      growth regulator cytokinin, which also dramatically reduced hypocotyl cell
      elongation in the absence of light, did not prevent GUS-COP1 nuclear localization
      in dark-grown seedlings. Our results suggest that all of the previously
      characterized pleiotropic COP/DET/FUS loci are required for the proper nuclear
      localization of the COP1 protein in the dark, whereas the less pleiotropic
      COP/DET loci or plant regulators tested are likely to act either downstream of
      COP1 or by independent pathways.

PMID- 9232870
TI  - Cytoplasmic free Ca2+ in Arabidopsis roots changes in response to touch but not
      gravity.
AB  - Changes in cytoplasmic Ca2+ concentration ([Ca2+]i) have been proposed to be
      involved in signal transduction pathways in response to a number of stimuli,
      including gravity and touch. The current hypothesis proposes that the development
      of gravitropic bending is correlated with a redistribution of [Ca2+]i in
      gravistimulated roots. However, no study has demonstrated clearly the development
      of an asymmetry of this ion during root curvature. We tested this hypothesis by
      quantifying the temporal and spatial changes in [Ca2+]i in roots of living
      Arabidopsis seedlings using ultraviolet-confocal Ca(2+)-ratio imaging and
      vertical stage fluorescence microscopy to visualize root [Ca2+]i. We observed no
      changes in [Ca2+]i associated with the graviresponse whether monitored at the
      whole organ level or in individual cells in different regions of the root for up
      to 12 h after gravistimulation. However, touch stimulation led to transient
      increases in [Ca2+]i in all cell types monitored. The increases induced in the
      cap cells were larger and longer-lived than in cells in the meristematic or
      elongation zone. One millimolar La3+ and 100 microM verapamil did not prevent
      these responses, whereas 5 mM EGTA or 50 microM ruthenium red inhibited the
      transients, indicating an intracellular origin of the Ca2+ increase. These
      results suggest that although touch responses of roots may be mediated through a
      Ca(2+)-dependent pathway, the gravitropic response is not associated with
      detectable changes in [Ca2+]i.

PMID- 9232872
TI  - Changes in the level and activation state of the plasma membrane H(+)-ATPase
      during aging of red beet slices.
AB  - The effect of aging on the plasma membrane (PM) H(+)-ATPase of red beet (Beta
      vulgaris L.) parenchyma discs was analyzed in PM purified by aqueous two-phase
      partitioning. Aging increased both the activity in the amount of immunodetectable
      H(+)-ATPase in the PM. The activity assayed at slightly alkaline pH values
      increased earlier and more strongly than that assayed at acidic pH values, so
      that the pH curve of the enzyme from aged beet discs was shifted toward more
      alkaline values. Aging decreased the stimulation of the PM H(+)-ATPase activity
      by controlled trypsin treatments or by lysophosphatidylcholine. After trypsin
      treatment the pH dependence of H(+)-ATPase from dormant or aged beet discs became
      equal. These results indicate that aging not only increases the level of H(+)
      ATPase in the PM, but also determines its activation, most likely by modifying
      the interaction between the autoinhibitory carboxyl-terminal domain and the
      catalytic site. When the PM H(+)-ATPase activity was assayed at a slightly
      alkaline pH, the tyrosine modifier N-acetylimidazole inhibited the H(+)-ATPase in
      the PM from dormant beet discs much less than in the PM from aged discs,
      suggesting that modification of a tyrosine residue may be involved in the
      activation of the PM H(+)-ATPase induced by aging. The results are discussed with
      regard to aging-induced development of transmembrane transport activities.

PMID- 9232873
TI  - The N-terminal propeptide of the precursor to sporamin acts as a vacuole
      targeting signal even at the C terminus of the mature part in tobacco cells.
AB  - An asparagine-proline-isoleucine-arginine-leucine (NPIRL) and its related
      sequences in the N-terminal propeptides (NTPP) of several plant vacuolar
      proteins, including that of sporamin from sweet potato (SPO) function as vacuole
      targeting determinants in a manner that is distinct from the vacuole-targeting
      determinant in the CTPPs of other plant vacuolar proteins. When the mutant
      precursor to sporamin, SPO-NTPP (in which NTPP was moved to the C terminus of the
      mature part), was expressed in tobacco (Nicotiana tabacum) cells, the pro-form
      was efficiently targeted to the vacuole and the NTPP was cleaved off. Unlike the
      results obtained with the wild-type precursor, substitution of the NPIRL sequence
      in the C-terminally located NTPP to asparagine-proline-glycine-arginine-leucine
      in the SPO-isoleucine-28-to-glycine mutant resulted in missorting of less than
      20% of the pro-form to the medium. Unlike the vacuolar transport of SPO-NTPP, the
      vacuolar transport of SPO-isoleucine-28-to-glycine was strongly inhibited by 33
      microM wortmannin, which is similar to the C-terminal propeptide-mediated
      vacuolar transport. These results suggest that the vacuole-targeting function of
      the NPIRL sequence is not strictly dependent on its location at the N terminus of
      a protein and that the C-terminally located mutant NTPP acquired some
      physicochemical properties of the C-terminal vacuole-targeting sequence.

PMID- 9232871
TI  - Membrane lipid unsaturation modulates processing of the photosystem II reaction
      center protein D1 at low temperatures.
AB  - The role of membrane lipid unsaturation in the restoration of photosystem II
      (PSII) function and in the synthesis of the D1 protein at different temperatures
      after photoinhibition was studied in wild-type cells and a mutant of
      Synechocystis sp. PCC 6803 with genetically inactivated desaturase genes. We show
      that posttranslational carboxyl-terminal processing of the precursor form of the
      D1 protein is an extremely sensitive reaction in the PSII repair cycle and is
      readily affected by low temperatures. Furthermore, the threshold temperature at
      which perturbations in D1-protein processing start to emerge is specifically
      dependent on the extent of thylakoid membrane lipid unsaturation, as indicated by
      comparison of wild-type cells with the mutant defective in desaturation of 18:1
      fatty acids of thylakoid membranes. When the temperature was decreased from 33
      degrees C (growth temperature) to 18 degrees C, the inability of the fatty acid
      mutant to recover from photoinhibition was accompanied by a failure to process
      the newly synthesized D1 protein, which accumulated in considerable amounts as an
      unprocessed precursor D1 protein. Precursor D1 integrated into PSII monomer and
      dimer complexes even at low temperatures, but no activation of oxygen evolution
      occurred in these complexes in mutant cells defective in fatty acid unsaturation.

PMID- 9232874
TI  - Antisense expression and overexpression of biotin carboxylase in tobacco leaves.
AB  - The plastid acetyl-coenzyme A carboxylase (ACCase) catalyzes the first committed
      step of fatty acid synthesis and in most plants is present as a heteromeric
      complex of at least four different protein subunits: the biotin carboxylase (BC),
      the biotin carboxyl carrier protein, and the alpha and beta subunits of the
      carboxyltransferase. To gain insight into the subunit organization of this
      heteromeric enzyme complex and to further evaluate the role of ACCase in
      regulating fatty acid synthesis, BC expression was altered in transgenic plants.
      Tobacco (Nicotiana tabacum) was transformed with antisense-expression and
      overexpression tobacco BC constructs, which resulted in the generation of plants
      with BC levels ranging from 20 to 500% of wild-type levels. Tobacco plants
      containing elevated or moderate decreases in leaf BC were phenotypically
      indistinguishable from wild-type plants. However, plants with less than 25% of
      wild-type BC levels showed severely retarded growth when grown under low-light
      conditions and a 26% lower leaf fatty acid content than wild-type plants. A
      comparison of leaf BC and biotin carboxyl carrier protein levels in plants with
      elevated and decreased BC expression revealed that these two subunits of the
      plastid ACCase are not maintained in a strict stoichiometric ratio.

PMID- 9232875
TI  - Antisense expression of the peptide transport gene AtPTR2-B delays flowering and
      arrests seed development in transgenic Arabidopsis plants.
AB  - Previously, we identified a peptide transport gene, AtPTR2-B, from Arabidopsis
      thaliana that was constitutively expressed in all plant organs, suggesting an
      important physiological role in plant growth and development. To evaluate the
      function of this transporter, transgenic Arabidopsis plants were constructed
      expressing antisense or sense AtPTR2-B. Genomic Southern analysis indicated that
      four independent antisense and three independent sense AtPTR2-B transgenic lines
      were obtained, which was confirmed by analysis of the segregation of the
      kanamycin resistance gene carried on the T-DNA. RNA blot data showed that the
      endogenous AtPTR2-B mRNA levels were significantly reduced in transgenic leaves
      and flowers, but not in transgenic roots. Consistent with this reduction in
      endogenous AtPTR2-B mRNA levels, all four antisense lines and one sense line
      exhibited significant phenotypic changes, including late flowering and arrested
      seed development. These phenotypic changes could be explained by a defect in
      nitrogen nutrition due to the reduced peptide transport activity conferred by
      AtPTR2-B. These results suggest that AtPTR2-B may play a general role in plant
      nutrition. The AtPTR2-B gene was mapped to chromosome 2, which is closely linked
      to the restriction fragment length polymorphism marker m246.

PMID- 9232876
TI  - Protein phosphorylation as a mechanism for osmotic-stress activation of sucrose
      phosphate synthase in spinach leaves.
AB  - Experiments were performed to investigated the mechanism of sucrose-phosphate
      synthase (SPS) activation by osmotic stress in darkened spinach (Spinacia
      oleracea L.) leaves. The activation was stable through immunopurification and was
      not the result of an increased SPS protein level. The previously described Ca(2+)
      independent peak III kinase, obtained by ion-exchange chromatography, is
      confirmed to be the predominant enzyme catalyzing phosphorylation and
      inactivation of dephosphoserine-158-SPS. A new, Ca(2+)-dependent SPS-protein
      kinase activity (peak IV kinase) was also resolved and shown to phosphorylate and
      activate phosphoserine-158-SPS in vitro. The peak IV kinase also phosphorylated a
      synthetic peptide (SP29) based on the amino acid sequence surrounding serine-424,
      which also contains the motif described for the serine-158 regulatory
      phosphorylation site; i.e. basic residues at P-3 and P-6 and a hydrophobic
      residue at P-5. Peak IV kinase had a native molecular weight of approximately
      150,000 as shown by gel filtration. The SP29 peptide was not phosphorylated by
      the inactivating peak III kinase. Osmotically stressed leaves showed increased
      peak IV kinase activity with the SP29 peptide as a substrate. Tryptic 32P
      phosphopeptide analysis of SPS from excised spinach leaves fed [32P]inorganic P
      showed increased phosphorylation of the tryptic peptide containing serine-424.
      Therefore, at least part of the osmotic stress activation of SPS in dark leaves
      results from phosphorylation of serine-424 catalyzed by a Ca(2+)-dependent, 150
      kD protein kinase.

PMID- 9232877
TI  - Differential effect of purified spruce chitinases and beta-1,3-glucanases on the
      activity of elicitors from ectomycorrhizal fungi.
AB  - Two chitinases (EC 3.2.1.14) and two beta-1,3-glucanases (EC 3.2.1.39) were
      purified from the culture medium of spruce (Picea abines [L.] Karst.) cells to
      study their role in modifying elicitors, cell walls, growth, and hyphal
      morphology of ectomycorrhizal fungi. The 36-kD class I chitinase (isoelectric
      point [pl] 8.0) and the 28-kD chitinase (pl 8.7) decreased the activity of
      elicitor preparations from Hebeloma crustuliniforme (Bull. ex Fries.) Quel.,
      Amanita muscaria (L.) Pers., and Suillus variegatus (Sw.: Fr.) O.K., as
      demonstrated by using the elicitor-induced extracellular alkalinization in spruce
      cells as a test system. In addition, chitinases released monomeric products from
      the walls of these ectomycorrhizal fungi. The beta-1,3-glucanases (35 kD, pl 3.7
      and 3.9), in contrast, had little influence on the activity of the fungal
      elicitors and released only from walls of A. muscaria some polymeric products.
      Furthermore, chitinases alone and in combination with beta-1,3-glucanases had no
      effect on the growth and morphology of the hyphae. Thus, it is suggested that
      apoplastic chitinases in the root cortex destroy elicitors from the
      ectomycorrhizal fungi without damaging the fungus. By this mechanism the host
      plant could attenuate the elicitor signal and adjust its own defense reactions to
      a level allowing symbiotic interaction.

PMID- 9232878
TI  - Sex determination in dioecious Silene latifolia. Effects of the Y chromosome and
      the parasitic smut fungus (Ustilago violacea) on gene expression during flower
      development.
AB  - We have embarked on a molecular cloning approach to the investigation of sex
      determination in Silene latifolia Poiret, a dioecious plant species with
      morphologically distinguishable sex chromosomes. One of our key objectives was to
      define a range of genes that are up-regulated in male plants in response to Y
      chromosome sex-determination genes. Here we present the characterization of eight
      male-specific cDNA sequences and classify these according to their expression
      dynamics to provide a range of molecular markers for dioecious male flower
      development. Genetically female S. latifolia plants undergo a partial sex
      reversal in response to infection by the parasitic smut fungus Ustilago violacea.
      This phenomenon has been exploited in these studies; male-specific cDNAs have
      been further categorized as inducible or noninducible in female plants by smut
      fungus infection. Analysis of the organ-specific expression of male-specific
      probes in male and female flowers has also identified a gene that is regulated in
      a sex-specific manner in nonreproductive floral tissues common to both male and
      female plants. This observation provides, to our knowledge, the first molecular
      marker for dominant effect of the Y chromosome in nonreproductive floral organs.

PMID- 9232879
TI  - Effects of a mechanical stimulation of localization of annexin-like proteins in
      Bryonia dioica internodes.
AB  - Mechanical stimulation exerted by rubbing a young internode of Bryonia dioica
      plants inhibits its growth. Previous cellular and biochemical studies showed that
      this growth inhibition is associated with Ca(2+) redistribution and profound
      modifications of plasma membrane characteristics. We extracted and purified
      Ca(2+)-dependent phospholipid-binding proteins from B. dioica internodes. Two
      main proteins, p33 and p35, and other minor bands were isolated and identified as
      annexin-like proteins because of their biochemical properties and their cross
      reactions with antibodies against maize (Zea mays L.) annexins. Rabbit antiserum
      was obtained by injection of B. dioica p35. This antiserum was used for the
      immunocytolocalization of annexin-like proteins in internode parenchyma cells. It
      appeared that the distribution of annexin-like proteins was different before and
      30 min after the mechanical stimulation. Western analysis of proteins in membrane
      fractions after separation by free-flow electrophoresis showed that p35 was
      present in most fractions, whereas p33 appeared mainly in plasmalemma-enriched
      fractions after the mechanical stimulation. It is hypothesized that a subcellular
      redistribution of these proteins might be involved in growth inhibition by
      mechanical stress.

PMID- 9232880
TI  - Calmodulin-stimulated Ca(2+)-ATPases in the vacuolar and plasma membranes in
      cauliflower.
AB  - The subcellular locations of Ca(2+)-ATPases in the membranes of cauliflower
      (Brassica oleracea L.) inflorescences were investigated. After continuous sucrose
      gradient centrifugation a 111-kD calmodulin (CaM)-stimulated and caM-binding
      Ca(2+)-ATPase (BCA1; P. Askerlund [1996] Plant Physiol 110: 913-922; S.
      Malmstrom, P. Askerlund, M.G. Plamgren [1997] FEBS Lett 400: 324-328) comigrated
      with vacuolar membrane markers, whereas a 116-kD caM-binding Ca(2+)-ATPase co
      migrated with a marker for the plasma membrane. The 116 kD Ca(2+)-ATPase was
      enriched in plasma membranes obtained by aqueous two-phase partitioning, which is
      in agreement with a plasma membrane location of this Ca(2+)-ATPase.
      Countercurrent distribution of a low-density intracellular membrane fraction in
      an aqueous two-phase system resulted in the separation of the endoplasmic
      reticulum and vacuolar membranes. The 111-kD Ca(2+)-ATPase co-migrated with a
      vacuolar membrane marker after countercurrent distribution but not with markers
      for the endoplasmic reticulum. A vacuolar membrane location of the 111-kD Ca(2+)
      AtPase was further supported by experiments with isolated vacuoles from
      cauliflower: (a) Immunoblotting with an antibody against the 111-kD Ca(2+)-ATPase
      showed that it was associated with the vacuoles, and (b) ATP-dependent Ca2+
      uptake by the intact vacuoles was found to be CaM stimulated and partly
      protonophore insensitive.

PMID- 9232881
TI  - Differential induction of pyruvate decarboxylase subunits and transcripts in
      anoxic rice seedlings.
AB  - In 2-d-old rice (Oryza sativa L.) seedlings subjected to anoxic stress, pyruvate
      decarboxylase (PDC) activity increased 9-fold during a 168-h period. A polyclonal
      PDC antiserum that recognized alpha- and beta-subunits was used to quantify PDC
      protein by an enzyme-linked immunosorbant assay and showed a 5.6-fold increase,
      suggesting that the anoxically induced enzyme has a higher specific activity than
      the PDC isoform present under normoxia. Immunoblot analysis showed that levels of
      both PDC subunits were induced by anoxia. Immunoprecipitation of proteins labeled
      in vivo during anoxic treatment demonstrated that the alpha-subunit was
      preferentially synthesized at the onset of anoxia. Two partial cDNAs, including a
      novel sequence, were cloned from a cDNA library made from seedlings subjected to
      anoxia for 6 h. Gene-specific probes used to quantify northern blots showed that
      two or three PDC mRNAs are differentially induced by anoxia in rice seedlings.
      Immunoprecipitation of in vitro translation products of mRNAs isolated a
      different times of anoxic treatment confirmed this findings Our results suggest
      that anoxic induction of rice PDC involves transcriptional and
      posttranscriptional regulation of gene expression as well as differences in
      enzyme characteristics.

PMID- 9232882
TI  - The ferredoxin-binding site of ferredoxin: Nitrite oxidoreductase. Differential
      chemical modification of the free enzyme and its complex with ferredoxin.
AB  - Spinach (Spinacea oleracea) leaf ferredoxin (Fd)-dependent nitrite reductase was
      treated with either the arginine-modifying reagent phenyl-glyoxal or the lysine
      modifying reagent pyridoxal-5'-phosphate under conditions where only the Fd
      binding affinity of the enzyme was affected and where complex formation between
      Fd and the enzyme prevented the inhibition by either reagent. Modification with
      [14C]phenylglyoxal allowed the identification of two nitrite reductase arginines,
      R375 and R556, that are protected by Fd against labeling. Modification of nitrite
      reductase with pyridoxal-5'-phosphate, followed by reduction with NaBH4, allowed
      the identification of a lysine, K436, that is protected by Fd against labeling.
      Positive charges are present at these positions in all of the Fd-dependent
      nitrite reductase for which sequences are available, suggesting that these amino
      acids are directly involved in electrostatic binding of Fd to the enzyme.

PMID- 9232883
TI  - A cDNA clone highly expressed in ripe banana fruit shows homology to pectate
      lyases.
AB  - A cDNA clone (Ban17), encoding a protein homologous to pectate lyase, has been
      isolated from a cDNA library from climacteric banana fruit by means of
      differential screening. Northern analysis showed that Ban17 mRNA is first
      detected in early climacteric fruit, reaches a steady-state maximum at the
      climacteric peak, and declines thereafter in overripe fruit. Accumulation of the
      Ban17 transcript can be induced in green banana fruit by exogenous application of
      ethylene. The demonstrates that expression of this gene is under hormonal
      control, its induction being regulated by the rapid increase in ethylene
      production at the onset of ripening. The deduced amino acid sequence derived from
      the Ban17 cDNA shares significant identity with pectate lyases from pollen and
      plant pathogenic bacteria of the genus Erwinia. Similarity to bacterial pectate
      lyases that were proven to break down the pectic substances of the plant cell
      wall suggest that Ban17 might play a role in the loss of mesocarp firmness during
      fruit ripening.

PMID- 9232884
TI  - A gene encoding a chloroplast-targeted lipoxygenase in tomato leaves is
      transiently induced by wounding, systemin, and methyl jasmonate.
AB  - We investigated the relationship between the expression of lipoxygenase (LOX)
      genes and the systemin-dependent wound response in tomato (Lycopersicon
      esculentum) leaves. A polymerase chain reaction-based approach was used to
      isolate two tomato Lox cDNAs, called TomLoxC and TomLoxD. Both TomLOXC and
      TomLOXD amino acid sequences possess an N-terminal extension of about 60 residues
      that were shown by in vitro uptake to function as transit peptides, targeting
      these proteins into the chloroplast. Within 30 to 50 min following wounding or
      systemin or methyl jasmonate treatments, the TomLoxD mRNA level increased and
      reached a maximum between 1 and 2 h. TomLoxC mRNA was not detectable in leaves
      and was not found following wounding, but it was found in ripening fruits,
      indicating that the two tomato Lox genes are regulated in different tissues by
      different processes. The results suggest that the TomLoxD gene is up-regulated in
      leaves in response to wounding and encodes a chloroplast LOX that may play a role
      as a component of the octadecanoid defense-signaling pathway.

PMID- 9232885
TI  - Regulation of acyltransferase activity in immature maize embryos by abscisic acid
      and the osmotic environment.
AB  - Maize (Zes mays L.) embryos, isolated from the developing seed and incubated in
      dilute buffer, show reduced triacylglycerol (TAG) synthesis, and accumulation
      stops after 24 h. Synthesis and accumulation can be maintained at high levels if
      the incubation medium contains abscisic acid (ABA) and/or a high osmotic
      concentration. Radiolabeled free fatty acids accumulate at higher levels in
      embryos that contain less TAG, and acetyl coenzyme A carboxylase activity remains
      essentially unchanged under all of the conditions tested. In contrast, the
      activities of the acyltransferases required for TAG synthesis remain high only in
      embryos incubated with ABA and/or a high osmotic concentration. Dose-response
      curves showed that 4 microM of ABA or mannitol at -1.0 MPa elicits a full
      response; both values are within the range considered to be physiological. The
      TAG synthesis capacity and discylglycerol acyltransferase activity lost by
      pretreatment of the embryos can be restored by re-exposure to ABA or high
      osmoticum. Germination is not involved because isolated scutellum halves showed
      the same changes in enzyme activity found in the whole embryo but did not
      germinate. Our results provide direct evidence for the regulation of TAG
      synthesizing activities in maize embryos by ABA and the osmotic potential of the
      environment.

PMID- 9232886
TI  - Secretion of active recombinant phytase from soybean cell-suspension cultures.
AB  - Phytase, an enzyme that degrades the phosphorus storage compound phytate, has the
      potential to enhance phosphorus availability in animal diets when engineered into
      soybean (Glycine max) seeds. The phytase gene from Aspergillus niger was inserted
      into soybean transformation plasmids under control of constitutive and seed
      specific promoters, with and without a plant signal sequence. Suspension cultures
      were used to confirm phytase expression in soybean cells. Phytase mRNA was
      observed in cultures containing constitutively expressed constructs. Phytase
      activity was detected in the culture medium from transformants that received
      constructs containing the plant signal sequence, confirming expectations that the
      protein would follow the default secretory pathway. Secretion also facilitated
      characterization of the biochemical properties of recombinant phytase. Soybean
      synthesized phytase had a lower molecular mass than did the fungal enzyme.
      However, deglycosylation of the recombinant and fungal phytase yielded
      polypeptides of identical molecular mass (49 kD). Temperature and pH optima of
      the recombinant phytase were indistinguishable from the commercially available
      fungal phytase. Thermal inactivation studies of the recombinant phytase suggested
      that the additional protein stability would be required to withstand the elevated
      temperatures involved in soybean processing.

PMID- 9232887
TI  - Study of lignification by noninvasive techniques in growing maize internodes. An
      investigation by Fourier transform infrared cross-polarization-magic angle
      spinning 13C-nuclear magnetic resonance spectroscopy and immunocytochemical
      transmission electron microscopy.
AB  - Noninvasive techniques were used for the study in situ of lignification in the
      maturing cell walls of the maize (Zea mays L.) stem. Within the longitudinal axis
      of a developing internode all of the stages of lignification can be found. The
      synthesis of the three types of lignins, p-hydroxyphenylpropane (H), guaiacyl
      (G), and syringyl (S), was investigated in situ by cross-polarization-magic angle
      spinning 13C-solid-state nuclear magnetic resonance, Fourier transform infrared
      spectroscopy, and immunocytochemical electron microscopy. The first lignin
      appearing in the parenchyma is of the G-type preceeding the incorporation of S
      nuclei in the later stages. However, in vascular bundles, typical absorption
      bands of S nuclei are visible in the Fourier transform infrared spectra at the
      earliest stage of lignification. Immunocytochemical determination of the three
      types of lignin in transmission electron microscopy was possible thanks to the
      use of antisera prepared against synthetic H, G, and the mixed GS dehydrogenative
      polymers (K. Ruel, O. Faix, J.P. Joseleau [1994] J Trace Microprobe Tech 12: 247
      265). The specificity of the immunological probes demonstrated that there are
      differences in the relative temporal synthesis of the H, G, and GS lignins in the
      different tissues undergoing lignification. Considering the intermonomeric
      linkages predominating in the antigens used for the preparation of the
      immunological probes, the relative intensities of the labeling obtained provided,
      for the first time to our knowledge, information about the macromolecular nature
      of lignins (condensed versus noncondensed) in relation to their ultrastructural
      localization and development stage.

PMID- 9232888
TI  - Synthesis of 4-aza-5,6-dimethylbenzimidazole and biosynthetic preparation of 4-
      and 7-aza-5,6-dimethylbenzimidazolylcobamide.
AB  - We report on the preparation of 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6
      dimethyl-7-azabenzimidazolylcobamide. These vitamin B12-analogs were required as
      reference compounds for comparison with a corrinoid previously isolated in small
      amounts for Eubacterium limosum grown in the presence of 4(5)-aminoimidazole.
      4(7)-Aza-5,6-dimethylbenzimidazole was synthesized from N-1-benzyl-4
      nitroimidazole which was reduced to N-1-benzyl-4-aminoimidazole and condensed
      with 1-dimethylamino-2-methylbutan-3-one to yield N-1-benzyl-4-aza-5,6
      dimethylbenzimidazole. The benzyl group of this compound was split off by
      catalytic hydrogenation to form 4(7)-aza-5,6-dimethylbenzimidazole. 4(7)-Aza-5,6
      dimethylbenzimidazole was transformed by a growing culture of Propionibacterium
      shermanii into 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6-dimethyl-7
      azabenzimidazolylcobamide. Both vitamin B12-analogs were almost as active as
      Vitamin B12 in a growth test with the vitamin B12-dependent Escherichia coli
      mutant DSM 4261.

PMID- 9232889
TI  - Pulvinatal, a novel bioactive metabolite from the basidiomycete Nidularia
      pulvinata (Schw.) Fr.
AB  - Pulvinatal (1) was isolated from fermentations of Nidularia pulvinata as an
      inducer of differentiation of HL-60 promyelocytic leukemia cells. Its structure
      was elucidated by spectroscopic methods. In addition, N. pulvinata was found to
      produce 2,4,5-trihydroxy-6-methyl-benzenecarbaldehyde (2) and orsellinic acid
      (3). Pulvinatal exhibits weak antifungal and only marginal cytotoxic activities.

PMID- 9232890
TI  - Benzoic acid accumulation in the Pinus thunbergii callus inoculated with the pine
      wood nematode, Bursaphelenchus xylophilus.
AB  - Phenylacetic acid (PA), a phytotoxic product of the bacteria accompanying the
      virulent nematode isolate OKD-3 was detected in the callus of Pinus thunbergii
      after inoculation with the nematode. The amount of PA detected was large enough
      to induced the formation and accumulation of benzoic acid (BA) and its conjugates
      in the callus. These results further support the hypotheses that PA is the
      pathogenic toxin and that the PA-producing bacterial strains accompanying the
      pathogenic nematode are the genuine pathogens of the pine wilt disease.

PMID- 9232892
TI  - Upstream parameters affecting the cell growth and xylitol production by Candida
      guilliermondii FTI 20037.
AB  - The effects of yeast extract (0-10 g/l), methanol (0-10% v/v), acetic acid (0-1.0
      g/l), furfural (0-0.5 g/l), glucose (0-30 g/l), inoculum age (15-70 h) and
      product concentration (18-230 g/l) on the xylose-xylitol conversion by Candida
      guilliermondii FTI 20037 were studied. The xylitol specific productivity
      increased about 35% at a yeast extract concentration of 1.0 g/l, whereas glucose
      showed a strong inhibitory effect on the xylitol production and a stimulating
      effect on the growth of C. guilliermondii. Methanol, acetic acid and furfural
      under the employed concentrations did not show any positive effect neither on the
      growth or on the xylose-xylitol conversion by the yeast. The inoculum age showed
      a strong influence on xylitol formation and the best fermentative parameters were
      attained using a 40-h inoculum age. A xylitol concentration in the fermentation
      medium higher than 80 g/l inhibited markedly the xylitol productivity by the
      yeast C. guilliermondii.

PMID- 9232891
TI  - Trypanosoma brucei: ecto-phosphatase activity present on the surface of intact
      procyclic forms.
AB  - The results presented in this paper indicate that procyclic forms of Trypanosoma
      brucei possess a phosphatase activity detected in the external cell surface able
      to hydrolyze about 0.7 nmol.mg-1.min-1 p-nitrophenylphosphate. A faster rate of
      hydrolysis was observed when membrane-enriched fractions were used. This activity
      is weakly sensitive to 1 mM NaF, 10 mM tartrate and 10 mM levamizole but strongly
      inhibited by 0.1 mM vanadate. Inhibition by both NaF and vanadate have a
      competitive character. This phosphatase activity decreases by increasing the pH
      from 6.8 to 8.4, a pH range in which cell viability was maintained during at
      least 1 hour. In the membrane-enriched fractions this phosphatase activity showed
      to be an acid phosphatase. In addition, intact cells could catalyze the
      dephosphorylation of [32P]phosphocasein phosphorylated at serine and threonine
      residues.

PMID- 9232893
TI  - Induction of single- and double-strand breaks in plasmid DNA by monoenergetic
      alpha-particles with energies below the Bragg-maximum.
AB  - The yield of single-strand breaks (ssb) and double-strand breaks (dsb) produced
      by alpha-particles at the end of their track in DNA-films was determined
      experimentally. Helium nuclei were accelerated to 600 keV in the 400 kV ion
      accelerator and scattered at a carbon target. The elastically scattered alpha
      particles with energies of 344 keV and 485 keV were used to irradiate
      supercircular plasmid DNA in vacuo. For the dosimetry of the alpha-particles a
      surface barrier detector was used and the energy distribution of the alpha
      particles determined. The energy loss of the particles in the DNA-layer was
      calculated. DNA samples were separated into the three conformational isomers
      using agarose gel electrophoresis. After fluorochromation the number of ssb and
      dsb per plasmid DNA molecule was established from the band intensities assuming
      the validity of Poisson statistics. Linear dose effect correlations were found
      for ssb and dsb per plasmid molecule. In the case of 344 keV-alpha-particles the
      yield of dsb was (8.6 +/- 0.9) x 10(-11) breaks/Gy x dalton. The ratio of ssb/dsb
      was 0.5 +/- 0.2. This is at least a factor of six larger than the ratio found in
      experiments with higher energy alpha-particles and from model calculations.
      Similar experiments with protons yielded a relative biological effectiveness
      (rbe) value of 2.8 for the induction of double-strand breaks by track end alpha
      particles.

PMID- 9232895
TI  - Serological characterization of Hungarian plum pox virus isolates.
AB  - Three Hungarian (no. 2, 4 and 9), and a Moldavian (K) plum pox virus isolates
      were compared with a characterized Spanish isolate (5.15) by RT-PCR, ELISA, dot
      blot and Western blot analysis. Monoclonal antibodies prepared against the
      external, intermediate and internal sequences of the coat protein of the Spanish
      isolate were able to differentiate the four isolates. Hungarian isolate No. 2
      proved to be serologically identical to the Spanish isolate, while No. 4 showed
      appreciable differences and No. 9 could be recognized only by the monoclonal
      antibodies representing the intermedial and internal parts of the coat protein. K
      isolate showed a more distant relationship to other isolates. Our experiment
      provided the first demonstration of the presence of D type isolates in Hungary.

PMID- 9232894
TI  - A particulate guanylate cyclase (EC 4.6.1.2) from growing yeast cells
      (Saccharomyces cerevisiae).
AB  - The detection of cGMP in yeast (Eckstein 1988), but lacking hints at guanylate
      cyclase from sequencing of the yeast genome, raised questions about existence,
      isoform, and regulation of guanylate cyclase from this organism. We found a
      particulate guanylate cyclase activity in yeast extracts, exhibiting properties
      of an integral membrane protein. Characteristics are: pH-optimum at pH 6.8,
      temperature-optimum around 60 degrees C, only slight stimulation by Mn2+.
      Sigmoidal enzyme kinetics indicate allosteric regulation, ATP and Ca2+ act as
      negative allosteric effectors. The enzyme activity is increased by yeast alpha-1
      mating factor, and by sodium nitrite, thus showing properties of particulate as
      well as of soluble isoforms from other eukaryotes. The activation by alpha-1
      mating factor suggests receptor functions, and a role in ascospore conjugation.

PMID- 9232896
TI  - Is atmospheric superoxide vitally necessary? Accelerated death of animals in a
      quasi-neutral electric atmosphere.
AB  - To estimate the necessity of air ions (AIs) as a natural source of atmospheric
      gaseous superoxide for mammalia the effect of air ion deprivation on mice and
      rats was investigated. Ambient air deionization inside an experimental acrylic
      glass cage (AGC) was performed by electrostatic field, built up by acrylic glass
      surfaces. Under these conditions, four hours after the animals were placed into
      the AGC, the concentration of negative AIs was not detectable, the concentration
      of positive ions was (mean +/- SD) 77 +/- 18 ions x cm-3. The negative and
      positive AI concentrations in identical silicate glass cages (control) were 482
      +/- 128 ions x cm-3 and 660 +/- 148 ions x cm-3 respectively. It was found that
      the prolonged deficiency of AIs in ambient air leads to accelerated death of the
      animals. The life span of the deprived mice and rats was 16.2 +/- 0.9 and 23.0 +/
      1.1 days respectively. The pathological symptoms and ultrastructural changes in
      the adeno- and neurohypophysis in deprived animals observed strongly suggest that
      animal death is related to disturbances in neurohormonal regulation and pituitary
      insufficiency. The possible physiological need of AIs and atmospheric superoxide,
      and its role in the development of environmental stress in human beings and in
      particular in premature infants is discussed.

PMID- 9232897
TI  - Effect of cisplatin alone and in combination with gamma-radiation on the
      initiation of DNA synthesis in Friend leukemia cells.
AB  - The effect of the anticancer drug cisplatin (alone and in combination with gamma
      radiation) on the initiation of DNA synthesis in Friend leukemia cells was
      studied. A method for isolation of DNA fractions containing the origins of
      replication was used. It was found that cisplatin decreased the rate of the
      initiation of DNA synthesis. The mild gamma-radiation has previously been
      observed to inhibit the initiation of DNA synthesis. In the present investigation
      the combination of cisplatin and gamma-radiation showed additive effects without
      synergism on the initiation of DNA biosynthesis.

PMID- 9232898
TI  - Fluorescence of chromatin DNA induced by antitumoral naphthalimides.
AB  - Treatment of chicken blood smears and semithin sections from Epon-embedded mouse
      tissues with aqueous solutions of the 3-aminonaphthalimides FA-142, FA-2043, and
      FA-2143 induced a strong green-yellow fluorescence of chromatin under violet or
      violet-blue excitation. Chromatin emission was abolished by previous DNase or hot
      TCA treatment. The use of 3-methoxy (FA-655) and 3-nitro derivatives (M-4212 and
      M-12210) resulted in very weak fluorescence of chromatin. Absorption maxima at
      346 and 408 nm and an emission peak at 570 nm were observed for the free compound
      FA-142. Fluorescence properties open new and interesting applications for some of
      these antitumoral and DNA-intercalating naphthalimides.

PMID- 9232903
TI  - Retention of maize auxin-binding protein in the endoplasmic reticulum:
      quantifying escape and the role of auxin.
AB  - The localisation of maize (Zea mays L.) auxin-binding protein (ABP1) has been
      studied using a variety of techniques. At the whole-tissue level, tissue printing
      indicated that ABP1 is expressed to similar levels in all cells of the maize
      coleoptile and in the enclosed leaf roll. Within cells, the signals from
      immunofluorescence and immunogold labelling of ultrathin sections both indicated
      that ABP1 is confined to the endoplasmic reticulum (ER), none being detected in
      either Golgi apparatus or cell wall. This distribution is consistent with
      targeting motifs in its sequence. These observations are discussed with reference
      to the various reports which place a population of ABP1 on the outer face of the
      plasma membrane, including those suggesting that it is necessary on the cell
      surface for rapid, auxin-mediated protoplast hyperpolarisation. We have tested
      the ER, namely that auxin binding induces a conformational change in ABP1 leading
      to concealment of the KDEL retention motif. Using double-label immunofluorescence
      the characteristic auxin-induced rise in Golgi-apparatus signal was found, yet no
      change in the distribution of the ABP1 signal was detected. Maize suspension
      cultures were used to assay for auxin-promoted secretions of ABP1 into the
      medium, but secretion was below the limit of detection. This can be ascribed at
      least partly to the very active acidification of the medium by these cells and
      the instability of ABP 1 in solution below pH 5.0. In the insect-baculovirus
      expression system, in which cell cultures maintain pH 6.2, a small amount of ABP1
      secretion, less than 1% of the total, was detected under all conditions, Insect
      cells were shown to take up auxin and no inactivation of added auxin was
      detected, but auxin did not affect the level of ABP1 in the medium. Consequently,
      no evidence was found to support the model for auxin promotion of ABP1 secretion.
      Finally, quantitative glycan analysis was used to determine what proportion of
      ABP1 might reach the plasma membrane in maize coleoptile tissue. The results
      suggest that less than 15% of ABP1 ever escapes from the ER as far as the cis
      Golgi and less than 2% passes further through the secretory pathway. Such leakage
      rates probably do not require a specialised mechanism allowing ABP1 past the KDEL
      retrieval pathway, but we are not able to rule out the possibility that some ABP1
      is carried through associated with other proteins. The data are consistent with
      the presence of ABP1 both on the plasma membrane and in the ER. The relative
      sizes of the two pools explain the results obtained with immunofluorescence and
      immunogold labelling and illustrate the high efficiency of ER retention in
      plants.

PMID- 9232905
TI  - Identification of calreticulin-like protein as one of the phosphoproteins
      modulated in response to oligogalacturonides in tobacco cells.
AB  - Oligogalacturonide-induced modifications of protein phosphorylation in cells of
      Nicotiana tabacum L. were investigated by in-vitro phosphorylation of plasma
      membrane-enriched fractions and electrophoretic analysis on two-dimensional gels.
      About 100 polypeptides were resolved; among these 40 phosphoproteins were
      detected and their 33P-labelling quantified. Most of the phosphorylations were
      inhibited by staurosporine and several proteins were hyperphosphorylated in the
      presence of okadaic acid, indicating the presence of protein phosphatase(s) in
      addition to staurosporine-susceptible protein kinase(s) in the plasma-membrane
      enriched fraction. In the presence of oligogalacturonides, phosphorylation of
      seven acidic polypeptides ranging from 15 to 65 kDa was strongly enhanced. A
      twofold enhancement of the phosphorylation of 24-kDa protein and a two- to
      threefold decrease in the phosphorylation of acidic proteins of MrS 62, 65, 80
      and 84 was also observed in response to oligogalacturonides. One of the
      oligogalacturonide-modulated phosphoproteins was identified as calreticulin by
      direct nucleotide sequencing after preparative two-dimensional electrophoresis
      and comparison with protein database sequences. Decreased phosphorylation of
      calreticulin was also observed in vivo, shortly after addition of
      oligogalacturonides to tobacco cells, confirming the biological relevance of the
      modification. Although the presence of calreticulin, an abundant reticuloplasmin
      with high calcium-binding capacity, has been reported in both mammalian and plant
      cells, its function is as yet largely unknown. Modulation of the phosphorylation
      of a plant calreticulin-like protein by oligogalacturonides is shown here,
      suggesting a role in the early transduction steps of this signal.

PMID- 9232906
TI  - Cloning of the cDNA for glutaredoxin, an abundant sieve-tube exudate protein from
      Ricinus communis L. and characterisation of the glutathione-dependent thiol
      reduction system in sieve tubes.
AB  - Sieve-tube exudate protein (STEP) from Ricinus communis L. seedlings consists of
      a characteristic set of more than 100 different polypeptides, against which a
      complex antiserum was raised. This antiserum cross-reacted with dominant protein
      species (molecular weights 10-30 kDa) present in the sieve-tube exudate and, to a
      lesser extent, with proteins in tissue extracts of Ricinus and a wide range of
      other plant species. For further elucidation of the nature of individuals STEPs
      in the sieve tubes the anti-STEP serum was used to screen a cDNA expression
      library constructed from Ricinus cotyledon mRNA. Two clones that differed in the
      3' untranslated region encoded a protein of 11 kDa which showed striking homology
      to bacterial and eucaryotic glutaredoxin sequences. Glutaredoxin activity was
      confirmed for the recombinant protein after overexpression in Escherichia coli
      and characterised in detail in sieve-tube exudate. Michaelis Menten constants
      (Km) for reduced glutathione and cysteine were 2 mM and 50 microns, respectively.
      Besides L-cysteine, dehydroascorbate and protein disulphides were also reduced by
      the activity present in the sieve-tube exudate. Glutathione, which is the
      obligate donor of reduced thiols for glutaredoxin, was present in sieve-tube sap
      in millimolar concentrations (up to 3 mM) with a ratio of total to oxidised
      glutathione of 3:1. It is suggested that glutaredoxin and glutathione in sieve
      tubes prevent oxidative damage and may be involved in redox regulation of sieve
      tube proteins.

PMID- 9232907
TI  - Photosynthesis and fluorescence quenching, and the mRNA levels of plastidic
      glutamine synthetase or of mitochondrial serine hydroxymethyltransferase (SHMT)
      in the leaves of the wild-type and of the SHMT-deficient stm mutant of
      Arabidopsis thaliana in relation to the rate of photorespiration.
AB  - The regulation by photorespiration of the transcript level corresponding to
      plastidic glutamine synthetase (GS-2) was investigated in the leaves of
      Arabidopsis thaliana (L.) Heynh.. Photorespiration was suppressed by growing the
      plants in an atmosphere containing 300 Pa CO2. Suppression of photorespiration
      was demonstrated by the ability of the conditionally lethal serine
      hydroxymethyltransferase (SHMT)-deficient stm mutant of A. thaliana to grown
      normally under these conditions. In contrast to previous studies with bean or pea
      that were performed at very high CO2 partial pressure (2-4 kPa; Edwards and
      Coruzzi, 1989, Plant Cell 1:241-248; Cock et al., 1991, Plant Mol Biol 17: 761
      771), suppression of photorespiration during growth of A. thaliana in an
      atmosphere with 300 Pa CO2 had no effect of the leaf GS-2 transcript level. In
      the short term, neither suppression of photorespiration induced by the transfer
      of air-grown A. thaliana plants into a CO2-enriched atmosphere, nor an increase
      in the rate of photorespiration achieved by the transfer of high-CO2-grown A.
      thaliana plants into air resulted in a change in the GS-2 mRNA level. The absence
      of photorespiratory ammonium release in leaves of the stm mutant had no effect on
      the GS-2 transcript level. Overall, our data argue against a control by
      photorespiration of the A. thaliana leaf GS-2 mRNA pool. In contrast, regulation
      of the leaf SHMT mRNA level may involve a negative feedback effect of at least
      one metabolite derived from the glycine/serine conversion during
      photorespiration, as indicated by the overexpression of SHMT transcripts in the
      leaves of the stm mutant.

PMID- 9232908
TI  - Somatic embryogenesis in cultured immature zygotic embryos and leaf protoplasts
      of Arabidopsis thaliana ecotypes.
AB  - Immature zygotic embryos of six ecotypes (Nd-0, Ler, C24, Col-0, Nossen, Ws-2) of
      Arabidopsis thaliana (L.) Heynh. were cultured in vitro. The same ecotypes,
      except Nossen, were used for studies on leaf protoplast culture. Experimental
      conditions for the induction of somatic embryos were established in both culture
      systems. In the case of immature zygotic embryos, the parameters investigated
      were the influence of developmental stage of the explant, the ecotypes used, and
      various concentrations and combinations of growth regulatory substances
      (phytohormones). In the ecotype Ler, structures were discovered which were very
      similar to those found in the early stages of zygotic embryo-genesis: globular
      structures at the end of a suspensor-like single file of cells were frequently
      observed. In the case of leaf protoplasts, high efficiencies of colony formation
      and plant regeneration occurred in Ws-2 and C24. A novel type of cell division
      pattern was found in Col-0 and C24, again highly reminiscent of the early
      division patterns in zygotic embryos. Similarities and differences between
      zygotic and somatic embryogenesis are discussed.

PMID- 9232909
TI  - [Functional differentiation of human naive helper T cells].

PMID- 9232910
TI  - [Late phase reaction in atopic dermatitis--immunological parameters and
      immunohistological analysis].
AB  - We studied the correlation between late phase reaction (LPR) and laboratory data
      in atopic dermatitis (AD) and evaluated the pathological findings in LPR. We
      studied the correlation between LPR and the severity of AD, total IgE, specific
      IgE, total IgG4, specific IgG4 and eosinophils. There were correlations between
      immediate reaction (IR) and some laboratory data, but not between LPR and
      laboratory data. Pathological findings at 15 min 24 hrs and 48 hrs after dermal
      injection showed edema at 15 min, followed by epidermal eczematous changes in
      almost all cases at 24 hrs, edema and degeneration of dermal endothelial cells
      and surrounding connective tissue, and leukocytoclasia in half of the cases and
      deposition of C3 and IgG in parts. We found CD4+ cells in all layers of dermis, a
      greater ratio of EG2+ cells in deeper layers of dermis as time passed, and
      decrease of CD23+ cells after 24 hrs throughout the dermis. These changes were
      found in cases of IR-LPR+, too. It appears that the mechanism of LPR is complex
      and that IR is not indispensable, for LPR and that infiltration of CD4+ and EG2+
      cells throughout all layers of dermis are important, and these condition were
      related to subsequent reactions.

PMID- 9232911
TI  - [Clinical features of postinfectious chronic cough].
AB  - Postinfectious cough has been drawing attention as a factor involved in the
      etiology of chronic cough in the United States. In Japan, clinical features of
      postinfectious chronic cough (PICC) have not been described in detail. We
      investigated 22 patients with PICC diagnosed by the established criteria (Jpn. J.
      Allergol. 1995; 44: 1418). All patients were nonsmokers and none received ACE
      inhibitors. None had a history of atopy or sinus diseases. There were four men
      and 18 women with a median age of 65 years. These 22 patients underwent clinical
      examinations including chest roentgenograms, respiratory function tests,
      eosinophil counts in venous blood, serum IgE titers, antibody titers to
      Mycoplasma pneumoniae, sputum cytologic findings taken from ten patients, and
      histological features of bronchial biopsy specimens obtained from two patients;
      all findings were within normal limits. Clinical course of cough in 20 of the
      patients with PICC was evaluated using a cough diary. One patient did not keep a
      cough diary. Ten patients improved with dextromethorphan hydrobromide (D) and
      oxatomide (O). Three of the remaining 9 patients improved with Bakumondo-to (B)
      only, 4 with D+O+B, and 2 with D+O+B+ozagrel hydrochloride. The duration of cough
      before treatment showed a significant correlation with the time from the start of
      treatment to recovery (r = 0.47, p < 0.05). These results indicate that PICC
      tends to occur in elderly women and to improve with treatment combining with D,
      O, and B. We hope to establish a standard therapy for postinfectious chronic
      cough.

PMID- 9232912
TI  - [Effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isozyme type
      III/IV inhibitor, on the release of histamine from human peripheral leukocytes].
AB  - We studied the effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase
      (PDE) isozyme type III/IV inhibitor, and salbutamol on the release of histamine
      from activated human peripheral leukocytes. We stimulated the leukocyte
      suspensions with calcium ionophore A23187 (Ca-I, 10(-6 M) accompanied with SDZ
      ISQ 844 (10(-7) M, 10(-6) M, 10(-5) M), salbutamol (10(-7) M, 10(-6) M, 10(-5) M)
      and combination of SDZ ISQ 844 and salbutamol (10(-7) M, 10(-6) M, 10(-5) M), and
      measured the levels of histamine in the supernatant fluid and total cyclic AMP
      levels in the leukocyte suspensions. The increase of histamine levels induced by
      Ca-I was significantly inhibited by SDZ ISQ 844 (10(-6) M, 10(-5) M) in a dose
      dependent manner (p < 0.05, p < 0.01). Salbutamol at the concentration until 10(
      5) M did not inhibit the increase of histamine levels. Combination of SDZ ISQ 844
      and salbutamol significantly inhibited the increase of histamine levels (10(-6)
      M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The inhibition of
      the histamine release by SDZ ISQ 844 (10(-5) M was enhanced significantly by
      salbutamol (10(-5) M) (p < 0.05). Total cyclic AMP levels in the leukocytes
      suspensions increased significantly by SDZ ISQ 844 (10(-5) M) and combination of
      SDZ ISQ 844 and salbutamol (10(-6) M, 10(-5) M) in a dose-dependent manner (p <
      0.05, p < 0.01). The increase of cyclic AMP levels by SDZ ISQ 844 (10(-5) M) was
      enhanced by salbutamol significantly (p < 0.01). These results suggest that
      selective inhibition of PDE isozyme type III/IV protects the release of histamine
      from human activated leukocytes in connection with intracellular cyclic AMP
      levels and the protection is enhanced by beta-agonist.

PMID- 9232914
TI  - [A reformation of asthma diary].

PMID- 9232913
TI  - [A case of asthmatic patient with gastroesophageal reflux].

PMID- 9232915
TI  - HIV management in general practice.

PMID- 9232917
TI  - Self care for general practitioners.

PMID- 9232916
TI  - General practice and pharmacy.

PMID- 9232918
TI  - Alarm bells. When to worry about your patient with HIV.
AB  - General practitioners with little or no clinical experience of HIV infection may
      not be prepared when they are suddenly required to treat an HIV infected person.
      However, a thorough history, examination and assessment will quickly reveal if
      there are any emergencies that require urgent attention and specialist referral.

PMID- 9232919
TI  - Update on issues for HIV management.
AB  - During the past 12 months, there have been major advances in knowledge about HIV.
      With this new knowledge comes better management. In a very short period of time,
      both doctors and patients have swung from a mood of deep despondency to optimism
      and hopefulness. There have been several factors in this changed outlook: the
      availability of viral load testing; the licensing of new more potent anti
      retroviral drugs (particularly the protease inhibitors), and the demonstration
      (for the first time) that combination anti retroviral therapy offers benefit, not
      only in controlled clinical trials, but in the everyday lives of people living
      with HIV/AIDS.

PMID- 9232920
TI  - Why is testing for HIV so different?
AB  - An HIV test requires counselling, confidentiality and consent. The patient, the
      doctor or a third party may initiate it. Assessment of risk behaviours, rather
      than stereotyping into risk groups, is needed. Patients initiate tests after
      perceived risk behaviour, and other factors such as guilt or anxiety may prompt
      testing. Clinical cues such as fevers, weight loss, lymphadenopathy and
      candidiasis should alert general practitioners to possible HIV infection. General
      practitioners have a pivotal role in HIV testing and management.

PMID- 9232921
TI  - Antenatal HIV testing.

PMID- 9232922
TI  - HIV and STDs. Oral manifestations.
AB  - Many systemic diseases frequently have oral manifestations as one of their
      earliest signs, this is particularly so in the immunocompromised patient or as an
      indicator of a sexually transmitted disease. Without careful examination of the
      face, oropharynx and regional lymph nodes, diagnosis may be delayed, resulting in
      morbidity and in some cases mortality. This paper discusses oral lesions
      resulting from infection and their management.

PMID- 9232923
TI  - GPs and the care of people with AIDS.
AB  - General practitioners can play a pivotal role in coordinating care in AIDS. Along
      with a broad knowledge of diseases processes and treatments, they require an
      understanding of its psychosocial contexts and of the need for individualised
      care.

PMID- 9232925
TI  - Investigating stroke.

PMID- 9232924
TI  - Critical assessment of calcium antagonists.
AB  - Calcium antagonists have been demonstrated to be useful agents in the management
      of a wide variety of cardiovascular disorders. All calcium antagonists
      effectively lower blood pressure. Non dihydropyridine compounds (verapamil and
      diltiazem) are of particular benefit in the treatment of supraventricular
      arrhythmias and angina. Epidemiological data have raised concerns regarding the
      use of rapid acting dihydropyridine agents in the treatment of hypertension and
      ischaemic heart disease. Slow release agents provide sustained therapeutic
      benefits with fewer side effects than standard dihydropyridine preparations.

PMID- 9232926
TI  - Sports medicine. Chronic and debilitating pain in the groin.

PMID- 9232927
TI  - A case of syndrome X.
AB  - Type 2 diabetes is increasing in prevalence and is predominantly managed in
      general practice. This series contains case histories which deal with some of the
      metabolic problems that may be encountered in the management of these patients
      and indicates some of the many issues, other than glycaemic control, that need to
      be considered.

PMID- 9232929
TI  - The case of 4 year old Will.

PMID- 9232928
TI  - Onychomycosis.

PMID- 9232930
TI  - Sudden onset of febrile illness.

PMID- 9232931
TI  - Children's corner.

PMID- 9232932
TI  - The foot in diabetes.

PMID- 9232933
TI  - Cine magnetic resonance imaging, computed tomography and ultrasonography in the
      evaluation of chest wall invasion of lung cancer.
AB  - PURPOSE: To assess the usefulness of cine-magnetic resonance imaging (cine-MRI)in
      the evaluation of chest wall invasion, we compared the results of cine-MRI with
      those of computed tomography (CT) and ultrasonography (US). MATERIALS AND
      METHODS: Eleven patients were examined who had no pain and who were difficult to
      diagnose by routine examinations. MRI was performed with a Magnetom SP/4000, 1.5T
      unit (Siemens, Germany). For cine imaging, continuous turbo-FLUSH (ultra fast low
      angle shot) images were obtained at an orthogonal section to the chest wall
      during slow deep breathing. A CT scan was performed using a TCT 900S or Super
      Helix (Toshiba, Japan) at 1 cm intervals, with section thicknesses of 1 cm
      throughout the entire chest. US was performed with a model SSA-270A (Toshiba,
      Japan) with 7.5-MHz linear array scanners (PLF-705S; Toshiba, Japan). RESULTS:
      Sensitivity, specificity and accuracy were 67%, 75% and 73% for cine MRI, 67%,
      63% and 64% for CT, 33%, 75% and 64% for US, respectively. CONCLUSIONS: These
      results indicate that cine MRI is potentially useful for the diagnosis of chest
      wall invasion of lung cancer.

PMID- 9232934
TI  - Tumor-specific synergistic therapy of mitomycin C: modulation of bioreductive
      activation.
AB  - The bioreductive activation of mitomycin C (MMC) has been investigated using 10
      human cancer cell lines. Except for 2 lines (COLO201 and COLO320DM), the cellular
      NAD(P)H: quinone oxidoreductase (DTD) activities correlated well with MMC-induced
      DNA damage and cytotoxicity. In addition, when the DTD activity was inhibited
      with 50 mM dicoumarol, the MMC activity decreased significantly. On the other
      hand, no correlation between the NADPH cytochrome P450 reductase (P450) activity
      and MMC efficacy was observed. We postulate that two electron reduction by DTD
      may be more important in MMC activation than one electron reduction by P450. The
      DTD-mediated metabolism was pH-dependent. In a nude mouse experimental model, the
      pH in the tumor decreased under hyperglycemic conditions due to unique
      glycolysis. The administration of m-iodobenzyl-guanidine (MIBG) enhanced the
      decrease in the pH of the tumor without affecting the pH of normal tissue
      (liver). It also significantly increased the antitumor activity of MMC. However,
      this biochemical modulation had no effect in the COLO201 and COLO320DM cells.
      Other mechanisms may be involved in the regulation of MMC activity in these
      cells. In conclusion, DTD may be an important target of MMC. Biochemical
      modulation using MIBG and glucose may selectively enhance the activity of MMC
      within cancer cells.

PMID- 9232935
TI  - Role of intercellular adhesion molecule-1, lymphocyte function-associated antigen
      1, and macrophages in ddY mouse nephropathy.
AB  - ddY mouse nephropathy is an animal model of human IgA nephropathy that is
      characterized by spontaneous IgA deposition in the glomerular mesangium,
      mesangial cell proliferation, and matrix expansion. We investigated the
      involvement of intercellular adhesion molecule-1, lymphocyte function-associated
      antigen-1, and macrophages in the pathogenesis of ddY mouse nephropathy. Five
      mice each underwent urinalysis, light microscopic examination of the kidneys,
      immunofluorescent detection of immunoglobulins and complement, and
      immunohistochemical examination for intercellular adhesion molecule-1, lymphocyte
      function-associated antigen-1, and infiltrating macrophages at 5, 10, 20, 30, 40,
      50, 60, and 70 weeks of age. Albuminuria was observed from the age of 20 weeks
      and all mice showed albuminuria by 70 weeks. Histological glomerular damage was
      significantly related to the appearance of albuminuria (p < 0.01). In the
      glomeruli, positivity for intercellular adhesion molecule-1 and lymphocyte
      function-associated antigen-1, as well as the number of infiltrating macrophages,
      were significantly increased in mice with nephropathy compared to pre-nephropathy
      mice (p < 0.01). These results suggest that intercellular adhesion molecule-1,
      lymphocyte function-associated antigen-1, and infiltrating macrophages are
      involved in the progression of histological damage in ddy mouse nephropathy.

PMID- 9232937
TI  - New on the Net.

PMID- 9232936
TI  - The usefulness of gastric mass screening using serum pepsinogen levels compared
      with photofluorography.
AB  - Chronic atrophic gastritis, which is though to be a high risk for gastric cancer,
      can be diagnosed by serum pepsinogen levels. We compared the usefulness of the
      measurement of pepsinogen levels and indirect photofluorography as indicators of
      gastric cancer in a mass screening involving 5,620 Japanese subjects (mean age:
      60.1 years old; male : female = 2,268:3,352) in 1991 and 1992. Subjects with a
      serum pepsinogen I level below 30 micrograms/liter or a pepsinogen I/II ratio
      below 2.0 were considered to be at high risk of gastric cancer. The incidence of
      gastric cancer and the ratio of early cancers detected by pepsinogen levels
      (0.12%, 4/7) were similar to those detected by photofluorography (0.11%, 4/6).
      Our results showed that mass screening using pepsinogen levels was as useful as
      indirect photofluorography for the detection of gastric cancer in Japan. In
      addition, our results showed that the sensitivity of gastric mass screening was
      increased when the measurement of serum pepsinogen levels was combined with
      photofluorography.

PMID- 9232939
TI  - IMS survey reflects physicians' concerns, future needs.

PMID- 9232938
TI  - Alternative medicine.
AB  - Much attention is given to alternative and complementary therapies by the media
      and our patients. Well over 40% of the US population uses some form of
      unconventional (not allopathic or osteopathic) medical care. This feature focuses
      on the role of spirituality and other mind-body therapies in healing.

PMID- 9232940
TI  - Is prevention of sudden infant death syndrome now a reality?

PMID- 9232942
TI  - Musculoskeletal examination needs to be a matter of habit.

PMID- 9232943
TI  - Informing public, students will make profession 'visible'.

PMID- 9232944
TI  - Advances in the treatment of superficial fungal infections: focus on
      onychomycosis and dry tinea pedis.
AB  - Onychomycosis is one of the most stubborn superficial mycoses. With few
      exceptions, oral antifungal therapy is needed to achieve resolution. Before oral
      itraconazole, fluconazole, and terbinafine hydrochloride became available,
      physicians had to rely on prolonged therapy with griseofulvin or oral
      ketoconazole. Of the newer oral agents, itraconazole appears to have the broadest
      spectrum of action, with therapeutic activity against dermatophytes, yeasts, and
      some nondermatophyte molds. Tissue pharmacokinetics accounts for significantly
      greater efficacy and much shorter treatment courses for fungal infections of the
      skin and nails. In general, oral itraconazole, fluconazole, and terbinafine are
      very well tolerated. The newer oral agents offer improved efficacy over
      griseofulvin and ketoconazole for onychomycosis and dry tinea pedis.

PMID- 9232945
TI  - Chest pain and the role of somatic dysfunction.
AB  - The symptom of chest pain may be a result or manifestation of somatic dysfunction
      of the musculoskeletal system. Chest pain is a common chief complaint among
      patients in a family practice office or in the emergency room. Various
      intrathoracic and extrathoracic factors may be responsible. The authors describe
      their experience with one patient in whom osteopathic manipulative treatment was
      used along with accepted medical tests and therapy to diagnose and treat this
      patient. If chest pain is effectively diagnosed and promptly treated, OMT can
      provide the most thorough, cost-effective, and satisfying care available.

PMID- 9232946
TI  - Neuroleptic malignant syndrome: case report and review.
AB  - Neuroleptic malignant syndrome is a rare but potentially fatal disorder that has
      been associated with the use of antipsychotic medications. Because neuroleptic
      malignant syndrome is rare, clinicians often have a low index of suspicion for
      the disorder which may lead to delayed treatment and increased mortality. This
      article describes a case of neuroleptic malignant syndrome and briefly reviews
      current diagnostic criteria and treatment options.

PMID- 9232947
TI  - Comparing medical knowledge of osteopathic medical trainees in DO and MD
      programs: a random effect meta-analysis.
AB  - The authors used random effect meta-analysis to synthesize eight mean score
      differences of the Part III/Level 3 examinations of the national Board of
      Osteopathic Medical Examiners (NBOME) between osteopathic medical trainees in DO
      residency programs and osteopathic medical trainees in MD programs. The analysis
      involved 6001 trainees and all Part III or Level 3 examinations since 1992. The
      average mean score difference was not significantly different from zero; however,
      the estimates of true effect sizes of each examination varied substantially. The
      findings indicate that, overall, medical knowledge of osteopathic trainees in MD
      and DO residency programs is compatible at the time they took the examinations.
      However, a large variation of effect size suggests the need for further
      investigation of the factors other than difference between osteopathic and
      allopathic training programs.

PMID- 9232948
TI  - A fatal illness presenting as an S1 radiculopathy. Vascular causes of lumbar
      radicular pain.
AB  - Lower extremity radiculopathy usually originates from abnormal changes in the
      spinal canal, such as herniated nucleus pulposus, degenerative spinal stenosis,
      or spondylolisthesis. Multiple cases have been reported in which lower extremity
      neurologic symptoms were associated with a vascular abnormality in the abdomen or
      pelvis. Femoral and obturator neuropathies and lumbosacral radiculopathies have
      been described as presenting signs of complicated aortic and iliac aneurysms. We
      present an unusual case of a nonruptured aortoiliac aneurysm with erosion into
      the spinal canal and neuroforamina which presented as a lumbosacral radiculopathy
      secondary to direct compression of nerve roots. The unsuspected presence of a
      major vascular structure in an atypical location could have catastrophic
      consequences in the fact of instrumentation. In patients with known or suspected
      aortoiliac aneurysms, CT or MRI evaluation of the spine should be performed as
      the initial diagnostic evaluation of new radicular pain.

PMID- 9232949
TI  - The role of surgery in the treatment of benign liver lesions.

PMID- 9232950
TI  - Lt Governor Stephen L. Henry, MD. Physician, politician, persona.

PMID- 9232951
TI  - Kennedy/Kassebaum: what physicians should know about this new law.

PMID- 9232952
TI  - Current recommendations for empiric therapy for tuberculosis.

PMID- 9232953
TI  - Neonatal renal artery blood flow velocities using color Doppler ultrasonography.
AB  - BACKGROUND: It is essential to evaluate the renal function for the management of
      high risk neonates. Color Doppler ultrasound technique can provide a useful
      information to evaluate the neonatal renal artery blood flow velocities. This
      study was performed to obtain the normative data of renal blood flow velocities
      in preterm and fullterm neonates and to compare the renal blood flow velocities
      with the aortic blood flow velocities. The normal volumetric state of fluid
      balance and renal function are essential in the management of the sick neonates.
      METHODS: The renal peak systolic blood flow velocity (renal PSFV), the renal mean
      blood flow velocity (renal MFV), the renal end diastolic blood flow velocity
      (renal EDFV) and the renal resistance index (renal RI) and also the cardiac
      output, the aortic peak systolic blood flow velocity (aortic PSFV) and the aortic
      mean blood flow velocity (aortic MFV) were serially recorded from one to 7 days
      after birth in 16 preterm and one to 5 days in 23 normal fullterm neonates.
      RESULTS: The renal PSFV was significantly increased with the postnatal age, and
      the renal MFV was significantly increased between three and five days of age in
      the preterm neonates. In the fullterm neonates there was no significant change of
      the renal PSFV between one and five days of age, but the renal MFV was
      significantly increased between three and five days of age. There were no
      statistically significant differences of the renal PSFV, the renal MFV, the renal
      EDFV and the renal RI between the preterm and the fullterm neonates in the first
      five days after birth. The cardiac output in the preterm neonates was higher than
      that in the fullterm neonates: on day 3; 313 +/- 59 vs. 254 +/- 40 ml/kg/min. (p
      < 0.001) and on day 5; 357 +/- 95 vs. 280 +/- 35 ml/kg/min. (p < 0.01). The renal
      blood flow velocities were not significantly correlated with the aortic blood
      flow velocities in the normal fullterm neonates, whereas, in the preterm neonates
      the renal PSFV correlated with the cardiac output (r = 0.35, p < 0.01), the
      aortic PSFV (r = 0.45, p < 0.001) and the aortic MFV (r = 0.39, p < 0.01), and
      the renal MFV also correlated with the aortic PSFV (r = 0.30, p < 0.05) and the
      aortic MFV (r = 0.32, p < 0.05). CONCLUSIONS: The increased renal flow velocities
      with the postnatal age in the preterm infants might depend on the increased
      cardiac output.

PMID- 9232954
TI  - Regulation of selenoprotein P mRNA expression in comparison with metallothionein
      and osteonectin mRNAs following cadmium and dexamethasone administration.
AB  - Selenium is recognized as an essential trace element and an antidote for
      carcinogens, heavy metals etc., and also as an environmental pollutant causing
      dysfunction of both the brain and peripheral tissues. Selenoprotein P (SelP)
      contains 10 selenium per molecule in the form of selenocysteines. To clarify
      whether SelP involved in selenium requirement and toxicity, SelP mRNA expression
      was compared with the expression of metallothionein (MT) and osteonectin (OST)
      mRNAs, the protein products of which are known to have antidote effects. MT and
      OST are induced by diverse forms of stress and immediately affect genes with
      stress promoter sequences. Cd and dexamethasone were used to examine such
      secondary regulation. Basal expression of SelP mRNA was high both in NRK cells
      and in rat kidney and brain but dexamethasone induction was observed only in NRK
      cells. Dexamethasone, but not Cd, decreased expression of OST mRNA in NRK cells,
      while OST mRNA in the kidney and brain increased after Cd administration in rats.
      Induction of MT mRNA was observed in response to Cd and dexamethasone in all
      cells and tissues examined, while the net increase was little because its basal
      expression was faint. Moreover, in situ hybridization indicated that SelP mRNA
      expression was localized to the cerebellum, one of the targets of selenium
      toxicity. The cerebellum is also a target for methyl-Hg intoxication, symptoms of
      which are ameliorated by selenium. Thus, SelP seems to be involved in both
      selenium homeostasis and detoxication mechanisms even though SelP mRNA is not
      always inducible.

PMID- 9232955
TI  - Retrograde cerebral perfusion with pharmacological cerebral protection in the
      repair of aortic arch aneurysm.
AB  - Twenty-six patients underwent resection and graft replacement of an aortic arch
      aneurysm (proximal arch,5; transverse arch:2, distal arch,8; and type A
      dissecting aneurysm. Retrograde cerebral perfusion with pharmacological cerebral
      protection was carried out during aortic arch aneurysm surgery. Prostaglandin E1,
      thiopental methylpredonisolone were administered for cerebral protection during
      core cooling. D-Mannitol and deferoxamine mesylate (radical scavengers) were
      administered for prevention of reperfusion injury. retrograde cerebral perfusion
      time was 48 +/- 16 minutes (range 20-80 minutes). Perfusion flow was 288 +/- 93
      mL/min (range 150-500 mL/min). Since retrograde cerebral perfusion requires no
      arterial cannulation or aortic cross clamp, the operative field is simplified,
      and the risks of air and debris emboli to the brain were minimized.
      Reconstruction was designed to minimize the circulatory arrest time. Eleven cases
      underwent emergency surgery due to rupture and acute dissection. Five patients
      (19.2%) died (three from bleeding from the distal anastomosis, one from
      postoperative DIC and, one from intraoperative dissection). The remaining 21
      patients survived neurologically intact. Retrograde cerebral perfusion with
      pharmacological cerebral protection is a very simple method to prevent air
      embolism or thromboembolism in aortic arch aneurysm surgery and allows aortic
      arch replacement in a bloodless field. In spite of the extended circulatory
      arrest time, recovery of consciousness was complete.

PMID- 9232956
TI  - Projections from the subdivisions of the fastigial nucleus to the vestibular
      complex and the prepositus hypoglossal nucleus in the albino rat: an anterograde
      tracing study using biocytin.
AB  - Differential projections from the subdivisions of the fastigial nucleus to the
      vestibular complex and the prepositus hypoglossal nucleus were investigated by an
      anterograde tracing method using biocytin in the albino rat. The caudomedial
      subdivision of the nucleus projected ipsilaterally to the dorsal and medial parts
      of the superior vestibular nucleus (Su Ve), the dorsomedial part of the lateral
      vestibular nucleus (LVe), and the dorsal parts of the medial (MVe) and spinal (Sp
      Ve) vestibular nuclei, and projected contralaterally to the ventrolateral corners
      of the Su Ve and LVe, the ventral part of the MVe, and the lateral part of the Sp
      Ve. The bilateral prepositus hypoglossal nuclei received sparse projections from
      the caudomedial subdivision. The middle subdivision of the fastigial nucleus
      projected ipsilaterally to the dorsal and/or ventral parts of the Su Ve, the
      dorsomedial pats of the LVe and Sp Ve, and the dorsolateral part of the MVe, and
      projected contralaterally to the dorsal margin of the Su Ve, the ventrolateral
      part of the LVe, and the lateral part of the Sp Ve. The dorsolateral protuberance
      of the fastigial nucleus projected ipsilaterally to the dorsal margin of the Su
      Ve, the dorsomedial part of the LVe, the dorsal or lateral parts of the Sp Ve,
      and the lateral part of the MVe, and projected contralaterally to the
      ventrolateral part of the LVe and the lateral part of the Sp Ve. The subnuclei x,
      y, and f, interstitial nucleus of the vestibular nerve, and the infracerebellar
      nucleus received bilateral or ipsilateral fastigiovestibular projections.

PMID- 9232957
TI  - [Analysis of genes implicated in osteogenic signaling by osteogenic protein-1 (OP
      1) using differential display method].
AB  - Bone morphogenetic proteins (BMPs), members of a transforming growth factor-beta
      (TGF-beta) superfamily, are growth and differentiation factors which induce
      ectopic bone formation in vivo. Although many studies on osteoinductive
      properties of BMPs have been conducted, little is known about the downstream
      components in the signal transduction machinery, beyond the mechanism of BMP
      receptor activation. In this study, the osteogenic effects by osteogenic protein
      1 (OP-1, BMP-7) on osteoblastic cell line MC3T3-E1 and murine stromal cell line
      ST2 were investigated, especially focusing on differentially expressed genes
      induced by OP-1 using the differential display method. The major findings were as
      follows: 1) Alkaline phosphatase specific activities of both MC3T3-E1 and ST2
      increased in a dose-dependent manner by OP-1 stimulation. 2) Northern analysis
      showed a significant increase of osteocalcin mRNA after 7 days of OP-1 treatment.
      3) 77 genes, which were differentially expressed in MC 3 T 3-E1 and ST 2 cells,
      were detected on differential display fingerprints after 16-hour treatment of OP
      1. 4) Some of these clones showed high levels of identical to known genes. 5) One
      clone called ST3v, down-regulated in ST2 cells by OP-1 stimulation, was confirmed
      with quantitative RT-PCR.

PMID- 9232958
TI  - [Denture mobility of complete dentures during function].
AB  - The purpose of this study was 1) to verify and apply a system to measure the
      three-dimensional (3-D) movement of the upper and lower complete dentures and the
      movement of the mandible with six degrees of freedom, and 2) to analyze the
      relationship between denture movements and the path of closure of the mandible
      during functions. A 3-D motion capture system with four infrared TV cameras was
      used for this purpose. The loci of each of three targets on the subject's head,
      the upper dentures, the lower dentures, and the mandible were measured three
      dimensionally. The relationship between the lower dentures and the mandibular
      movements was analyzed in the change of the inner product of normal vectors of
      the denture occlusal planes and mandibular planes. The results were as follows:
      This system could measure the denture mobility within 3.5 x 10(- 1) mm in error.
      The mobility of the upper dentures had a correlation to the path of closure of
      the mandible regardless of the working side or nonworking side, and the lower
      dentures had a tendency to move toward the working side.

PMID- 9232959
TI  - [Observations on structure of bone in human mandibular condyles with osteophyte
      formation].
AB  - The purpose of this study was to investigate the functional characteristics of
      human mandibular condyles from a morphological viewpoint. The structure of bone
      in the human mandibular condyles with osteophyte formation was observed
      macroscopically and microscopically and compared with that in the condyles which
      seemed to be normal. The following observations were made: 1. Generally, it was
      observed that remodeling seemed to occur frequently in compact bone in the joint
      surface area of the mandibular condyle. 2. As the distribution of lamellar bone,
      nonlamellar, and bundle bone in the joint surface area changes, the compact bone
      seems to shift down and protrude forward. In larger osteophytes, trabeculae of
      cancellous bone-like structure are observed. However, the basic structure of
      compact bone, including haversian system and the interlamellae structure remains
      within the trabecullae. Therefore, observation revealed histologically that this
      is a compact bone. The macroscopical appearance of cancellous bone-like structure
      seems to be a result of functional demand. 4. It was concluded that the
      mandibular condyles accommodate the functional loads, and adoptational changes
      occur constantly in a stable manner.

PMID- 9232960
TI  - [A study on tapping movements of patients with cerebral palsy].
AB  - The purpose of this study was to examine the deviation of tapping points and
      electromyographic activity in patients with cerebral palsy. The subjects in this
      study were 6 normal subjects as the control group and 4 subjects with cerebral
      palsy as the patient group. Twenty tapping movements and electromyographic
      activities in the bilateral masseter, anterior temporal, anterior digastric, and
      sternocleidomastoid muscles were recorded simultaneously with Gnatho-Hexagraph.
      The results were as follows: 1. The differences of the opening distance and the
      cycle of tapping movements between the patient group and the control group were
      not significant, but coefficients of variation of the patient group were greater
      than those of the control group. 2. The deviations of tapping points in the
      patient group were significantly greater anteroposteriorly, laterally, and
      vertically than those in the control group. 3. In the patient group,
      electromyographic activities of masseter and sternocleidomastoid muscles during
      tapping movements were significantly greater than those in the control group. 4.
      In the patient group, electromyographic activities of the anterior temporal
      muscles were significantly less symmetric than those in the control group.

PMID- 9232961
TI  - [Modulation of evoked potentials following electrical tooth and finger
      stimulation at selective attention task].
AB  - To investigate the effect of attention and novelty change of stimulus, modulation
      of evoked potentials following electrical tooth stimulus (EP-TS) and finger
      stimulus (EP-FS) by selective attention task were studied in 17 healthy adult
      volunteers. Stimulus in this study were electrical tooth and finger stimulus,
      tone beep in constant (2.0 sec.) interval in random order, and delivering
      percentage of tooth and finger stimulus was 10, 20, 30, 40, and 50% and tone beep
      was 80, 60, 40, 20, and 0%. The results were as follows: 1) P2 latency and N 2-P2
      amplitude were increased while the subject's attention was toward each stimulus
      (attention), decreased while the subject's attention was not toward each stimulus
      (non-attention) at EP-TS and EP-FS. 2) When paying attention, P 2 latency and N 2
      P 2 amplitude were increased as delivering percentage of tooth and finger
      stimulus were decreased. These findings suggested that attention and novelty
      change of stimulus when paying attention were one of the factors that influence
      psychological factors and modulate EP-TS and EP-FS results.

PMID- 9232962
TI  - [A fundamental study on assessment of gingival blood flow].
AB  - The purpose of this study was to establish the assessment of gingival blood flow
      by laser Doppler flowmeter (LDF) using three parameters; Velocity, Volume, and
      Flow. The gingival blood flow (GBF) at the labial attached gingiva of the
      maxillary incisor was measured by LDF in 10 healthy subjects, 3 men and 7 women.
      There were inter- and intra-individual variations in the obtained data. CV
      (coefficient of variance) values in each parameter of GBF while resting were as
      follows; Velocity: 10.2 approximately 34.5%, Volume:7.7 approximately 45.6%, and
      Flow: 15.4 approximately 67.6%. The effects of changing position, cold stimulus,
      and the vasoconstrictor (0.1w/v% epinephrine) on GBF were assessed. All three
      parameters significantly decreased (p < 0.01) after the cold stimulus. When the
      position was changed to the sitting position from the lying one, however, there
      were significantly decrease in Velocity (p < 0.001) and Flow (p < 0.02). On the
      other hand, the local application of the vasoconstrictor caused significant
      decrease in Volume (p < 0.01) and Flow (p < 0.01). Consequently, Flow
      significantly decreased after all the stimuli in the present study, however, the
      change of Velocity and Volume were variable depending on the type of stimulus.
      These results suggested that multiple parameters are needed for precise
      observation and analysis of blood flow.

PMID- 9232963
TI  - [Study on effects of mouth guard on ventilation].
AB  - To investigate the effects of the mouthguard on ventilation, including
      respiratory frequency (F), tidal volume (VT), oxygen uptake (VO2), respiratory
      exchange ratio (R), maximal oxygen uptake (VO2 max), and all-out time, an
      exercise tolerance test with modified Bruce's protocol was performed on 4 male
      subjects. Cumulative (cum.) value was also analyzed on F, VT, VO2, and R.
      Respective values with the mouthguard was compared to those without the
      mouthguard. The results are as follows: 1. F, VT, VO2, and R did not show a
      certain tendency among the 4 subjects. 2. Cum.F at all-out time was decreased 2
      approximately 8% among 3 subjects and increased 10% in 1 subject. 3. Cum.VT at
      all-out time was decreased 11 approximately 12% among 3 subjects and increased
      21% in 1 subject. 4. Cum. VO2 at all-out time was decreased 2 approximately 11%
      among 3 subjects and increased 20% in 1 subject. 5. Cum. R at all-out time was
      decreased 3 approximately 13% among 3 subjects and increased 10% in 1 subject. 6.
      VO2 max showed significant increase in 1 subject. 7. All-out time was decreased 3
      approximately 4% among 3 subjects and increased 9% in 1 subject.

PMID- 9232964
TI  - [Study for searching equilibrium point in dentulous hemimandibulectomy patients].
AB  - Occlusal registration for prosthodontic rehabilitation in dentulous
      hemimandibulectomy patient has various difficulties due to mandibular
      instability. The purpose of this study was to find the occlusal contact position
      for remaining dentition to stabilize the hemiresected mandible during clenching.
      Three hemimandibulectomized subjects without surgical bony construction were
      selected and custom-made Gothic-arch typed apparatus was fabricated. Mandibular
      movements during clenching were recorded with jaw movement tracking device with
      six degrees of freedom. The results were as follows: 1. The direction of the
      mandibular rotation around each coordinate axis in 3-dimensional space during
      clenching was constant in each subject, regardless of stylus position. 2. The
      most stable points on the hemimandibules during clenching did not necessarily
      correspond to the mid-portion of the remaining dentition of the mandible. 3. When
      referred to the maxillary arch, the point was lined up within the distal half of
      the second premolar and the mesial third of the first molar in mid-sagittal plane
      along the long axis of the remaining dentition. 4. Rotational axis during
      clenching existed on the horizontal plane. 5. It was assumed that the most stable
      point of the mandible in a hemimandibulectomy patient may be useful in
      interocclusal registration in clinical dental practice.

PMID- 9232966
TI  - Reproductive schedules in a density-dependent recruitment model.
AB  - Understanding the mechanisms that regulate stability and oscillatroy behavior
      requires isolated studies of each of the mechanisms so that their effects can be
      recognized and measured when they are coupled in a system. The role of the shape
      of the reproductive schedule, including its time lag, in determining stability
      properties in an age-structured density-dependent recruitment continuous model is
      investigated. The results are independent of the strength of the density
      dependence. Under the assumption of rather simple reproductive schedules,
      explicit and implicit reproductive delays were found to have a destabilizing
      effect, whereas spreading the reproductive effort over larger intervals has a
      stabilizing effect. Moreover, the stability is determined solely by the interplay
      of the reproductive effort and by the ratio between the standard deviation of the
      maternity distribution and the mean age of reproduction. This ratio has a
      stabilizing effect.

PMID- 9232965
TI  - [4-year clinico-statistical observation of outpatients].
AB  - Clinico-statistical observations were made on the outpatients visiting the
      Department of Initial Diagnosis and Emergency, Faculty of Dentistry Hospital,
      Tokyo Medical and Dental University in 1986, 1987, 1989 and 1990. The following
      findings were obtained according to sex, age group, and chief complaints of new
      outpatients. Approximately 60% of the outpatients were female during the year
      examined. The number of outpatients tended to increase in March and to decrease
      during the winter. The largest number of new outpatients visiting the hospital
      was in the 20-24-year-old group in both males and females. In the female
      patients, the 50-54-year-old group had a relatively higher peak. The greatest
      chief complaint was tooth pain. Further, the chief complaint involving oral soft
      tissues was due to inflammation. The main disease diagnosed due to chief
      complaints was caries in the 20-29-year-old group, marginal periodontitis in the
      50-59, pericoronitis of wisdom tooth in the 20-29, temporomandibular joint
      problem in the < or = 19 and masticatory disturbance in the 60 < or = -year-old
      groups.

PMID- 9232968
TI  - Stochastic optimization algorithms of a Bayesian design criterion for Bayesian
      parameter estimation of nonlinear regression models: application in
      pharmacokinetics.
AB  - This article proposes three stochastic algorithms to optimize a Bayesian design
      criterion for Bayesian estimation of the parameters of nonlinear regression
      models; this criterion is the information expected from an experiment. The first
      algorithm is based on a stochastic version of the simplex with an adaptive
      sampling procedure. The others are stochastic approximation algorithms: the
      Kiefer-Wolfowitz and the pseudogradient algorithms. We first present the
      information criterion and the optimization algorithms. The efficiency of each
      algorithm for optimizing this Bayesian design criterion is then assessed by a
      simulation study for a nonlinear model assuming a discrete prior distribution. An
      application for designing an experiment to estimate the kinetics of radioiodine
      thyroid uptake is then proposed.

PMID- 9232967
TI  - A carcinogenesis model describing mutational events at the DNA adduct level.
AB  - A stochastic carcinogenesis model is proposed to describe a sequence of component
      mutational changes that constitute the G:C-->A:T base substitution. This paper
      provides the biological basis and mathematical formulation underlying the
      proposed model. In addition, the paper elaborates on a numerical approach for
      studying the cumulant functions, survival functions, and hazard functions of the
      model. Several numerical examples are given of potential applications of the
      model.

PMID- 9232969
TI  - Treatment of gunshot wounds.

PMID- 9232971
TI  - Vision 21 Delphi panel: senior Army Medical Service Corps Officers' vision of
      behaviors for success of future Medical Service Corps officers.
AB  - A Delphi study was conducted of Army senior Medical Service Corps leaders (O6s)
      to identify the expected behaviors and competencies needed to ensure that junior
      officers will achieve successful careers as Medical Service Corps officers in the
      21st century. A Delphi mailing was conducted in two phases. In the first
      iteration, 41 behaviors were identified to be of importance. In the second
      mailing, the 41 behaviors were rated for relative importance on a 7-point bipolar
      rating scale (1 = unimportant, 7 = most important). Comparisons were made between
      the ratings of administrative and biomedical scientific/technical (BS/T) series.
      Discriminant models developed to compare demographics between administrative and
      BS/T officers indicated that administrative officers had more time in grade,
      years of service, and professional military education, whereas BS/T officers
      reported significantly more civilian education. Minor differences among the two
      groups emerged for behavior ratings; however, the final priority order of
      behaviors reflected a high degree of consensus from both groups.

PMID- 9232970
TI  - The Tripler Tobacco-Cessation Program: predictors for success and improved
      efficacy.
AB  - This study analyzed differences in baseline, course of treatment, and post-quit
      variables of participants in a tobacco-cessation program to identify factors
      predictive of outcome that could be used as a focus for intervention. The program
      offered a 10-week course of transdermal nicotine replacement combined with
      education and cognitive/behavioral therapy in a group format at a major military
      medical center. Demonstrated differences were found among abstainers, early
      relapsers, and late relapsers in age-initiated tobacco use, use of liquor, levels
      of exhaled carbon monoxide at intake, tobacco use during the program, and
      perceived reasons for relapse. The abstinence rate at follow-up was 27%. Based on
      our findings, we discuss recommendations to improve treatment. This information
      is offered as a model to evaluate and improve the efficacy of established clinic
      based tobacco-cessation programs.

PMID- 9232972
TI  - Managing the challenges of role diversification in an interdisciplinary
      environment.
AB  - Advanced practice nurses are increasing in number. Such nurses include the nurse
      practitioner, clinical nurse specialist, nurse anesthetist, and nurse midwife.
      The roles of nurse practitioners and clinical nurse specialists have been
      recommended by the American Nurses Association to merge. The frustrations related
      to this merger are identified, and strategies are proposed to resolve them.
      Examples of military, civilian, and international models are provided.

PMID- 9232973
TI  - Skin cancer trends at Wilford Hall Medical Center.
AB  - Incidence rates for all skin cancers are increasing. The objective of this study
      is to review data on melanoma and nonmelanoma skin cancer from Wilford Hall
      Medical Center and identify and compare trends to published data. Records were
      reviewed by computer search of pathology records from 1986 to 1993, and analysis
      by total numbers diagnosed, age distribution, and site are described. Overall,
      our data agree with published material. We did not show an increased frequency of
      basal cell carcinoma, squamous cell carcinoma, or melanoma during this period.

PMID- 9232975
TI  - Fruit and vegetables in the service member's diet: data from military
      institutional feeding studies.
AB  - Previous surveys of the U.S. population have indicated that typical intakes of
      fruits and vegetables are substantially below recommended levels. Using data from
      nine dietary studies, we examined 798 service members who subsisted in government
      run feeding programs to determine how they differ from the general population.
      The findings of this retrospective investigation showed that an estimated 43% of
      service members met the minimum recommendation of five daily servings of fruit
      and vegetables compared with 6% of the general population. Among genders, more
      males had fruits and vegetables rich in carotenoids (22 vs. 10%), whereas a
      slightly higher proportion of females consumed cruciferous vegetables (14 vs.
      11%). Only 3% consumed no servings of vegetables, and 11% consumed no servings of
      fruits. Intake in overall quantity of fruits and vegetables was higher among
      service members, but further efforts are needed to increase consumption of
      cruciferous vegetables and fruits and vegetables rich in carotenoids.

PMID- 9232974
TI  - Combat trauma life support training versus the original advanced trauma life
      support course: the impact of enhanced curriculum on final student scores.
AB  - BACKGROUND: Within a military framework, the trauma course student, a young
      medical officer, is trained to become a trauma team leader and the first provider
      of medical aid. By adding battlefield medicine-related subjects to the basic
      Advanced Trauma Life Support (ATLS) course, as well as exercises tailored to the
      distinctive demands of military medicine, we could develop a special teaching
      unit: Combat Trauma Life Support (CTLS). The curriculum is basically the complete
      unchanged ATLS course of the American College of Surgeons enriched with lectures
      and practicums to fill the gap between the essentially civilian emergency
      department character of the ATLS course and the military tasks of the medical
      officer. PURPOSE OF STUDY: To compare the cognitive knowledge achievements of
      trauma course participants in the Israel Defence Force Medical Corps and to
      delineate the impact of the course type on students' written test results.
      DESIGN: A retrospective comparison analysis of pre- and post-course written test
      scores of 2,614 physicians who had participated in the ATLS and CTLS courses in
      the Israel Defence Force School of Military Medicine between 1990 and 1993.
      RESULTS: The analysis indicated that students who undertook the CTLS course
      achieved statistically better results in written tests (87.9 +/- 8.7 vs. 79.6 +/-
      11.4, R2 = 0.33). CONCLUSIONS: We conclude that the CTLS comprehensive curriculum
      provides an improved training basis for the complex task of army battlefield
      trauma care support.

PMID- 9232976
TI  - Injuries in Australian Army recruits. Part I: Decreased incidence and severity of
      injury seen with reduced running distance.
AB  - Three hundred fifty male recruits were randomly allocated to either the standard
      recruit training program (N = 180) or substituted a weighted march activity for
      all running periods in the physical training program (N = 170). There were no
      other differences in the formal training program. The incidence of injury was
      37.6 and 46.6% in the walk and run groups, respectively. The rate of injury was
      52.9/100 recruits in the walk group and 61.7/100 in the run group. The exposure
      incidence was 12.8/1,000 hours of physical training in the walk group and
      14.9/1,000 hours in the run group. There was no statistically significantly
      difference in the total number of injured recruits in the two groups (64 vs. 85,
      chi(2) = 2.90, p = 0.09, relative risk [RR] = 1.24). There were, however,
      significantly more lower-limb (43 vs. 75, chi(2) = 9.77, p = 0.0018, RR = 1.65)
      and knee injuries (15 vs. 35, chi(2) = 6.54, p = 0.011, RR = 2.14) in the Run
      group. Lower-limb injuries constituted 79.8% of all Run injuries and 61.1% of all
      Walk injuries. Injuries in the Run group produced more morbidity, with nearly
      double the number of days of restriction, hospitalization, and not fit for duty.
      Standardized morbidity rates showed an average of 5.4 days of restriction per
      injury in the Run group and 3.96 days of restriction per injury in the Walk
      group. Reduction of running distance in the physical training program resulted in
      significant reductions in both the incidence of lower-limb injury and the overall
      severity of injury.

PMID- 9232977
TI  - Injuries in Australian Army recruits. Part II: Location and cause of injuries
      seen in recruits.
AB  - Three hundred fifty male recruits were randomly allocated to either the standard
      recruit training program (N = 180) or substituted a weighted-march activity for
      all formal run periods (N = 170) in the physical training program. All injuries
      were seen at a single medical facility, and the cause, location, and severity of
      injury were recorded in the medical documents. Lower-limb injuries constituted
      79.8% of all Run injuries and 61.1% of all Walk injuries. Foot (18.9%), knee
      (16.7%), ankle (13.3%), and shoulder (8.9%) were the most common sites of injury
      in the Walk group. In the Run group, the most common sites were knee (32.1%),
      ankle (18.3%), foot (11.9%), and shin (7.3%). There were two stress fractures
      (tibial) in the Run group and none in the Walk group, giving the Run group an
      incidence of 1.1%. There were 10 medical discharges in the Walk group and 16 in
      the Run group. Ten (62.5%) of the Run and 2 (20%) of the Walk discharges were due
      to lower-limb causes. Of these, only 1 (10%) of the Walk and 4 (25%) of the Run
      injuries were not considered to be pre-existing conditions. Marching (30.0%),
      physical training (25.5%), and the obstacle course (11.1%) were the most frequent
      causes of injury in the Walk group. In the Run group, the leading causes were
      running (36.6%), physical training (19.2%), and the obstacle course (14.6%).
      Running was the major cause of knee injury in the Run group (17/35), whereas
      physical training was the major cause of knee injury in the Walk group (5/15).
      Running was also the major cause of other lower-limb injuries in the Run group
      (19/58), whereas marching was the major cause in the Walk group (19/50). Lower
      limb injuries were more frequent in the Run group, with running cited as the
      major cause of these injuries.

PMID- 9232979
TI  - The relationship between aerobic fitness and recovery from high-intensity
      exercise in infantry soldiers.
AB  - The relationship between aerobic fitness and recovery from high-intensity
      exercise was examined in 197 infantry soldiers. Aerobic fitness was determined by
      a maximal-effort, 2,000-m run (RUN). High-intensity exercise consisted of three
      bouts of a continuous 140-m sprint with several changes of direction. A 2-minute
      passive rest separated each sprint. A fatigue index was developed by dividing the
      mean time of the three sprints by the fastest time. Times for the RUN were
      converted into standardized T scores and separated into five groups (group 1 had
      the slowest run time and group 5 had the fastest run time). Significant
      differences in the fatigue index were seen between group 1 (4.9 +/- 2.4%) and
      groups 3 (2.6 +/- 1.7%), 4 (2.3 +/- 1.6%), and 5 (2.3 +/- 1.3%). It appears that
      recovery from high-intensity exercise is improved at higher levels of aerobic
      fitness (faster time for the RUN). However, as the level of aerobic fitness
      improves above the population mean, no further benefit in the recovery rate from
      high-intensity exercise is apparent.

PMID- 9232978
TI  - Injuries in Australian Army recruits. Part III: The accuracy of a pretraining
      orthopedic screen in predicting ultimate injury outcome.
AB  - Three hundred fifty male recruits were divided into two groups: Walk (N = 170)
      and Run (N = 180). A physical screen was performed before the commencement of
      recruit training consisting of a visual assessment of the feet looking for pes
      planus, pes cavus, and deformities of the toes. Each recruit was also asked if he
      had sustained any injury in the preceding 2 years. The visual findings and
      history of prior injury were noted and compared with actual injuries sustained
      during the 12-week training course. Fifty-three subjects in the Walk group and 54
      in the Run group were identified as being at risk as a consequence of the screen.
      The sensitivity of the screen for predicting the subsequent injury was 34.4% in
      the Walk group and 31.8% in the Run group. The specificity was 72.6 and 77.4% in
      the Walk and Run groups, respectively. The predictive value of the test was 44.9%
      in the Walk group and 50.9% in the Run group. When reinjury was examined, the
      sensitivities fell to 9.4% (Walk) and 4.7% (Run) and the specificities to 57.5%
      (Walk) and 50.5% (Run). The screen correctly identified only 1 of 10 medical
      discharges in the Walk group and 2 of 16 in the Run group. The screening
      examination had poor sensitivity, specificity, and predictive value, and more
      than half of those thought to be at risk did not subsequently sustain an injury.
      Anecdotal beliefs that improvements in medical screening would reduce recruit
      wastage were not borne out. Abnormalities of the foot (pes planus, pes cavus,
      hallux valgus) were not significant factors in the development of injury during
      recruit training.

PMID- 9232980
TI  - Pediatric thyroid carcinoma in the military population.
AB  - A 30-year review of the Armed Forces Tumor Registry revealed that of 3,126
      thyroid cancers on file, 82 were in the pediatric population. All of these cases
      were reviewed, and the mean age was found to be 13.8 years. There as a male-to
      female ratio of 1:2.3. At the time of diagnosis, 33% had regional nodes and 6%
      had distant metastasis. The malignancies were 60% papillary, 13% follicular, 10%
      papillary-follicular variant, and 6% medullary. Treatment included 41%
      lobectomies with or without isthmectomy, 27% total thyroidectomies with or
      without node sampling, 20% total thyroidectomies with neck dissections, and 12%
      surgical treatment not otherwise specified. Of the surgical patients, 30%
      received postoperative 131I ablation. An average patient follow-up of 8.6 years
      showed that 65 remained disease-free, 5 had disease, 1 was dead of disease, and
      10 were unknown. The results of our pediatric thyroid carcinoma review are
      compared with previously published figures.

PMID- 9232981
TI  - Military psychologists and the Partnership for Peace program in Albania.
AB  - A team of two military psychologists (the authors) traveled to Albania to provide
      training to Albanian military sociologists in psychological issues associated
      with peacekeeping deployment in connection with the North Atlantic Treaty
      Organization's Partnership for Peace program. The training, based on research
      conducted by the authors, emphasize the typical problems faced by peacekeepers.
      The information presented was adjusted to better meet the particular needs of the
      Albanians. Topics of primary interest to the Albanians are discussed with an
      emphasis on the Albanian cultural context. General lessons for future Partnership
      for Peace training are also presented.

PMID- 9232982
TI  - Predictors of students' success in the Medical Service Apprentice course.
AB  - This study assessed the predictors of students' success in the 383d Training
      Squadron's Medical Service Apprentice course at Sheppard Air Force Base, Texas.
      Correlation and regression analyses provided seven predictors of students'
      success. These predictors were the Armed Services Vocational Aptitude Battery
      Mechanical score, block 1 grade, block 3 grade, block 3 student hours, block 4
      grade, block 4 student hours, and National Registry Emergency Medical Technician
      Test 1 grade. From these predictors, researchers ascertained demarcation points
      to provide direction for instructors and students. Using this guidance, proactive
      intervention by instructors and the Student Learning Center will improve the
      success of Medical Service Apprentice course students. Further research conducted
      by the 882d Training Group to evaluate predictors of success will yield a
      seamless evaluation process. This process will establish an improved proactive
      educational system enhancing the career field selection process and the quality
      of student education.

PMID- 9232983
TI  - Contamination of diagnostic ophthalmic solutions in primary eye care settings.
AB  - Pharmaceutical agents and irrigating solutions are widely used in both optometric
      and ophthalmologic practices. Contamination of these containers or solutions
      could possibly pose some risk of infection to a patient. We set out to
      investigate the possible contamination of a representative sample of these
      containers in small office practices. Representative bottles of two diagnostic
      pharmaceutical agents and an irrigating solution were obtained from primary care
      optometric and ophthalmologic practices in the San Francisco-Oakland Bay area.
      These bottles were tested to investigate the rate of contamination and to
      identify the types of microorganisms in the contaminated solutions. Sixty total
      samples (proparacaine, tropicamide, and an irrigating solution) were randomly
      cultured, and 11.7% of the samples showed contamination. Pseudomonas cepacia,
      Staphylococcus epidermidis, Pseudomonas putida, and Streptococcus species were
      the predominant organisms isolated from the contaminated bottles. In addition, 17
      of the original 60 containers were further cultured for investigation of the
      dried residue particles around the threads of the containers. Of these 17
      containers, 13 (76.5%) tested positive for Staphylococcus and Micrococcus
      species.

PMID- 9232984
TI  - Identification and eradication of Helicobacter pylori in an isolated patient
      population.
AB  - This study had three goals: (1) Identify patients with Helicobacter pylori, treat
      their disease, monitor their progress, and determine that they are no longer
      infected. (2) Realize a cost savings for our health clinic. (3) Improve patient
      quality of life. These three goals have been met.

PMID- 9232985
TI  - Military service and pseudopseudohypoparathyroidism: recognizing red flags for
      rare medical conditions.
AB  - Pseudopseudohypoparathyroidism is a rare disorder characterized by normal serum
      parathyroid hormone, calcium, and phosphate and skeletal abnormalities (referred
      to as Albright's hereditary osteodystrophy) that include short stature, short
      digits, and heterotopic calcifications. Since each military recruit cannot be
      screened for every medical condition, unusual requests regarding fitness for duty
      might serve as red flags for rare medical conditions. This point is illustrated
      by the case history of an infantryman who served 22 years in the U.S. Marine
      Corps with pseudopseudohypoparathyroidism.

PMID- 9232986
TI  - [HIV infection and risk behaviour among prostitutes in the Amsterdam
      streetwalkers' district; indications of raised prevalence of HIV among
      transvestites / transsexuals].
AB  - OBJECTIVE: To determine the prevalence of HIV infection and risk behaviour among
      various groups of streetwalkers in Amsterdam and the extent of overlap between
      different prostitution networks. SETTING: The family room project in the
      streetwalkers' district in Amsterdam, the Netherlands. METHODS: In November 1996,
      saliva was taken from 32 female and 25 transsexual/transvestite prostitutes and
      tested for antibodies against HIV. Besides, prostitutes were interviewed on risk
      behaviour, history of sexually transmitted diseases and mobility. RESULTS: Only
      one of the participants (a female prostitute) had ever injected drugs. None of
      the female prostitutes, but 6 of the 25 transsexuals/transvestite prostitutes
      (24%; 95% confidence interval: 7-41) proved seropositive. None of the HIV
      infected participants was aware of his serostatus. The transsexual/transvestite
      prostitutes frequently had receptive anal intercourse with their clients. Condom
      use was high, but most did not use condoms made for anal intercourse. Female
      prostitutes also reported a high rate of condom use with their clients. Both
      groups of prostitutes reported few private partners and a low rate of condom use
      with these partners. According to the transsexual/transvestite prostitutes many
      of their clients had sexual contacts with women in their private lives. Many
      prostitutes thought that they shared the same clients in the district.
      CONCLUSION: HIV infections occur quite often among transsexual/transvestite
      prostitutes in the streetwalkers' district in Amsterdam. The risk of further
      spread HIV infection to their clients (and through them to other heterosexual
      populations) is present. AIDS education targeted at this group is important. The
      use of (special) condoms when having anal intercourse in private as well as in
      prostitution contacts should be emphatically advised.

PMID- 9232987
TI  - [Mediastinal lymph node metastasis from esophageal carcinoma: CT assessment with
      pathologic correlation].
AB  - Computed tomographic (CT) scans were performed in 179 patients with esophageal
      carcinoma to evaluate mediastinal lymph node metastasis. Histopathologic findings
      were compared with CT findings in a total of 7,218 resected lymph nodes. First,
      the criterion for lymph node metastasis on CT scans was 10 mm or more in long
      transverse diameter. The overall sensitivity and positive predictive value (PPV)
      were 19% (60 of 317 nodes) and 33% (60 of 180 nodes), respectively. Analysis of
      each of the eight subgroups of mediastinal nodes revealed that the PPV was more
      than 70% in node Nos. 105, 108, 110, and 112. In other subgroups, however, the
      PPV was less than 60%. Sensitivity was less than 50% in all eight subgroups.
      Second, the criterion for metastasis was 10 mm or more in short transverse
      diameter. The overall sensitivity and PPV were 8% (26 of 317 nodes) and 63% (26
      of 41 nodes), respectively. Analysis of subgroups showed that the PPV in No. 106
      nodes increased to 92%. In No. 106 nodes, use of a 5 mm criterion in long
      transverse diameter increased sensitivity to only 55%. Of the 317
      histopathologically proven metastatic lymph nodes, 90 nodes (28%) were 10 mm or
      more in size, 112 (35%) were 5-10 mm, and 115 (36%) were less than 5 mm. Of the
      6,901 non-metastatic lymph nodes, 473 nodes (7%) were 10 mm or more in size.
      Small (less than 5 mm in size) metastatic nodes were present in all eight
      subgroups. Among No. 107 and 109 nodes, large (10 mm or more in size)
      nonmetastatic nodes were prominent, resulting in low sensitivity and PPV. We
      conclude that CT does not provide an accurate assessment of metastatic versus non
      metastatic mediastinal lymph nodes in patients with esophageal carcinoma.

PMID- 9232988
TI  - [Tc-99m labeled leukocyte scintigraphy and CT for the evaluation of patients with
      inflammatory bowel disease].
AB  - Seventeen cases (11 patients) of inflammatory bowel disease (IBD) were studied to
      define the intensity and extent of disease by 99mTc-HMPAO-labeled leukocytes
      scintigraphy (TLLS), and 10 cases underwent CT examination to evaluate the bowel
      wall, lymph-nodes, and mesenteric surroundings. Serial TLLS were obtained up to 4
      hours and CT was carried out within one week before or after TLLS. The
      sensitivities of early (1 hour) and delayed (4 hours) TLLS were 91% and 100%,
      respectively. The respective specificities were 100% and 33%. However, it
      appeared that mild IBD may yield false negative results in early TLLS while non
      specific bowel activity and migration of white cells may cause false positive
      results in delayed imaging. By setting the diagnostic criteria for labeled
      leukocyte accumulation on visualization of the small bowel regardless of uptake
      or activity of the large bowel similar to or greater than lumbar bone marrow, the
      sensitivity and specificity of delayed TLLS changed to 91% and 83%, respectively.
      On CT examination, mesenteric lymph-node swelling, periintestinal blurring and
      dilatation of mesenteric vasa recta were observed in all five patients with
      active Crohn's disease, while wall thickening and enhancement were seen in four
      of them. None of the other three cases of inflammatory disease showed positive
      findings of dilatation of the mesenteric vasa recta, and they revealed relatively
      low uptake of labeled leukocytes in TLLS. A "scintigram score" was calculated by
      comparing uptake of tracer in five bowel segments with lumbar bone marrow
      activity, and a "CT score" was calculated by adding abnormalities of the
      intestine and mesenteric surroundings. The scintigram score correlated closely
      with CT score and clinical disease activity. Combined use of CT and TLLS for the
      evaluation of patients with IBD was an excellent means to obtain the findings of
      intensity and extent of disease of the bowel wall and mesenteric surroundings and
      provided useful information in determining the patient management.

PMID- 9232989
TI  - [CT-guided biopsy of small lung nodules: usefulness of frozen-section pathologic
      diagnosis].
AB  - PURPOSE: To improve the diagnostic accuracy of computed tomography (CT)-guided
      biopsy of small lung nodules. MATERIALS AND METHODS: The usefulness of fine
      needle core biopsy combined with immediate frozen-section diagnosis by
      pathologists was prospectively studied. Forty-six biopsies of small lung nodules
      (less than 3 cm in greatest diameter) were performed under CT guidance in 46
      patients with 31 malignant and 15 benign processes. Initial biopsy was always
      attempted with a 20 or 21G histological needle; tissue samples were sent to the
      pathology department immediately after biopsy for pathologic diagnosis of the
      frozen sections. RESULTS: In 41 of 46 lesions (89.1%), sufficient material was
      obtained for diagnosis, permitting a correct final diagnosis. For malignancy, the
      sensitivity was 100%, whereas 81.8% of the benign lesions were diagnosed as
      specifically benign. Pneumothorax occurred in 41.3%. CONCLUSION: Histological
      diagnosis using frozen sections is a useful adjunct for CT-guided biopsy of the
      chest.

PMID- 9232990
TI  - [Effectiveness of percutaneous transluminal angioplasty and intra-arterial
      papaverine infusion for symptomatic vasospasm after subarachnoid hemorrhage].
AB  - PURPOSE: To evaluate the clinical effectiveness of PTA and/ or intra-arterial
      infusion of papaverine (PPV) for the treatment of symptomatic vasospasm after
      subarachnoid hemorrhage. MATERIALS AND METHODS: From September 1989 to March
      1996, twenty patients with symptomatic vasospasm were treated by PTA and/or intra
      arterial infusion of PPV. Nine of the patients were treated by only PTA, eight by
      only PPV infusion, and three by both PTA and PPV infusion. Early clinical results
      were evaluated within 48 hours after treatment. Changes in the mean flow velocity
      (MFV) of the M1 segment as determined by TCD before and after treatment were also
      evaluated. RESULTS: Six of the nine patients (66.7%) treated only by PTA, six of
      the eight patients (75%) treated only by PPV, and all three patients (100%)
      treated by both PTA and PPV infusion showed improvement of neurological deficits
      within 48 hours after treatments. CONCLUSION: PTA was effective for main trunk
      vasospasm, while PPV infusion was more effective for peripheral severe vasospasm
      in recovery from neurological deterioration after subarachnoid hemorrhage. Use of
      both treatments further increased the effectiveness.

PMID- 9232991
TI  - [Effects of low-dose total body irradiation (TBI) on tumor-bearing rats].
AB  - To investigate the anti-tumor effects of low-dose total body irradiation (TBI)
      histologically, 5 x 10(5) KDH-8 cells were implanted into the right legs of WKAH
      rats. According to the treatment policies, rats were divided into four groups:
      non-treated, TBI alone, local irradiation (LI) following TBI, and LI alone. The
      total dose of TBI was 0.2 Gy, that of LI 10 Gy or 0.2 Gy. Local irradiation of
      0.2 Gy had no suppressive effect on the growth of implanted tumor and/or
      metastasis. In the 10 Gy LI group, growth of the implanted tumor was totally
      suppressed, and histological findings (H-E staining) showed that there were few
      viable cells, few tissue-infiltrating cells, and severe fibrotic changes in the
      tumor tissue. In the TBI group, tumor growth was suppressed during only 7 days
      after TBI. However, abundant tumor infiltrating cells appeared 24 hours after
      TBI. Total body irradiation did not enhance the suppressive effect of LI on tumor
      growth. Metastases of the lung and abdominal lymph nodes were significantly
      suppressed by TBI. In the TBI group, using the lung-shield with 5 cm lead block,
      the suppression of lung metastasis was the same as that in the non-shield TBI
      group. These results suggested that a low dose of TBI brings about anti-tumor
      effects through a host immune response, unlike those produced by high-dose
      irradiation.

PMID- 9232992
TI  - [Endemic fluorosis in southern China: radiological findings].
AB  - Fluorosis continues to be prevalent in the southern regions of China. The endemic
      fluorosis caused by inhalation of fluoride-containing coal dust etiologically
      contrasts with the common occurrence of endemic fluorosis due to the intake of
      fluoride-containing water. We investigated the radiologic findings in 49 affected
      individuals in a district of this region. More than 80% of patients exhibited
      radiologic evidence of skeletal fluorosis, and most patients belonged to stage 3
      of Singh and Jolly's classification. The most common skeletal abnormality was
      ossification of the interosseous ligaments in the extremities, which warranted
      radiographic examination of the limbs as a tool for screening.

PMID- 9232993
TI  - [Postgadolinium MR angiography of normal intradural veins of the thoracolumbar
      spine].
AB  - To evaluate the normal intradural spinal veins, we used postgadolinium three
      dimensional time-of-flight MR angiography (MRA) at 1.5T in 7 subjects. MR images
      and MR angiograms[32/6/1 (TR/TE/NEX)] were obtained after a bolus injection of Gd
      DTPA (0.15-0.2 mmol/kg). We reconstructed images using an equipped function, so
      called multiplanar reconstruction. The anterior median veins in 2 patients and
      the posterior median veins were shown in 2. The great medullary veins were
      demonstrated in 2. We successed in obtaining venous angiograms by postgadolinium
      MRA. Disseminated tumors and abnormal enhanced cauda equina are often
      indistinguishable from normal intradural veins. This study suggests that it is
      useful to know the MR angiographic features of normal intradural veins in order
      to evaluate enhanced intradural components.

PMID- 9232994
TI  - [Trial of a detachable Y-shaped tube with two valves for serial examinations of
      CT arterial portography and CT hepatic arteriography].
AB  - In five patients with hepatocellular carcinoma, CT arterial portography (CTAP)
      and CT hepatic arteriography (CTHA) were performed serially by using a newly
      developed detachable Y-shaped tube with two valves that could be attached to a
      conventional angiographic sheath. Two catheters could be inserted into the
      conventional angiographic sheath without blood backflow by using the Y-shaped
      tube. One catheter could be easily and safety placed on the common or proper
      hepatic artery, and the other on the superior mesenteric artery. This detachable
      Y-shaped tube with two valves could make it easy to perform serial CTAP and CTHA
      examinations.

PMID- 9232995
TI  - [Balloon-occluded ethanol ablation therapy: (BEAT) for hepatocellular carcinoma].
AB  - To obtain simultaneous embolization of feeding arteries and portal veins in the
      hepatocellular carcinoma, we performed a new treatment, balloon occluded ethanol
      ablation therapy (BEAT), in 7 patients. A Balloon catheter was inserted into the
      hepatic vein draining the tumor bearing segment of the liver. During occlusion of
      the hepatic vein by balloon catheter, an absolute ethanol-Lipiodol emulsion was
      injected through a microcatheter or a microballoon catheter placed in the feeding
      artery. There were no major side effects. Histological examination of the
      specimen taken from one case showed complete necrosis of the tumor and
      accumulation of Lipiodol within the portal veins of the surrounding tissue.

PMID- 9232996
TI  - [Trial of analysis of esophageal wall motion using optical flow method on
      esophagogram].
AB  - Several studies have indicated that the analysis of esophageal motion provides a
      valid means of identifying esophageal diseases. Although this motion can be seen
      on esophagogram, its quantification leaves much room for improvement. This study
      presents a computer method to quantify the apparent motion (optical flow)
      observed on sequences of esophagogram. This method computes at every point of a
      sequence of digitized images the two-dimensional velocity vector which
      characterized its motion from one image to the next image. The information on
      motion of the esophagus can be displayed by superimposing the local velocity
      vector on the original image.

PMID- 9232997
TI  - [Recent clinical applications of MR medicine as functional medical imaging in the
      brain and heart].
AB  - This paper reviewed recent clinical applications of MR medicine as functional
      imaging in the brain and heart. Functional and metabolic imaging of brain and
      heart can be evaluated by the development of fast MR technique (fast SE, echo
      planar imaging, etc) and chemical shift imaging. The clinical applications of MR
      medicine to the brain are follows. 1. higher nerve activity assessment using
      functional MRI, 2. brain perfusion imaging by dynamic contrast MRI, 3. brain
      diffusion imaging and 4. brain metabolic function by 1H and 31P-MRS. Those of MR
      medicine to the heart are as follows. 1. left ventricular function assessment by
      snapshot and/or echo planar imaging. 2. regional wall motion assessment by
      magnetic tagging, 3. myocardial perfusion imaging by dynamic contrast MRI, 4.
      coronary flow reserve assessment and 5. cardiac metabolic function by 31P and 1H
      MRS. Most of these data are thought to be compatible with nuclear medicine
      technique such as PET and SPECT. In the future, MR medicine may be used as the
      tool of functional and metabolic diagnosis in addition to anatomical diagnosis in
      the field of cerebral and cardiac disorders.

PMID- 9232998
TI  - [High-field (3.OT) MR system: advantages in functional analysis].
AB  - In order to elucidate the precise mechanisms underlying higher brain function,
      investigations need to focus not only on functionality of neuronal networks but
      also the underlying connectivity. Newly developed magnetic resonance (MR)
      techniques offer revolutional, non-invasive tools for both functionality and
      connectivity analysis in humans, namely, BOLD (blood oxygen level dependent)
      functional magnetic resonance imaging (MRI) and three dimensional anisotropy
      contrast (3DAC) magnetic resonance axonograpy (MRX). The former technique makes
      use of changes in regional deoxyhemoglobin concentration associated with brain
      function, while the latter utilizes directional information of apparent
      diffusivity observed in axonal fibers. In these critically important but highly
      demanding imaging techniques, high-field (> or = 3.OT) MR systems possess
      significant advantages over conventional systems.

PMID- 9232999
TI  - [Historical developments and present status of rapid NMR imaging].
AB  - Rapid NMR imaging methods are historically reviewed and their present status is
      introduced. Three major rapid imaging techniques, EPI, FLASH, and RARE (Fast SE),
      are described historically and their typical images are presented. Since some
      advanced rapid imaging techniques are often harmful to patients, it is suggested
      that future rapid imaging techniques must be developed to minimize the gradient
      switching speed and rf power deposition.

PMID- 9233000
TI  - [Technical aspects of fast, ultra-fast MR imaging].
AB  - Technical aspects of fast, ultra-fast MR imaging are described. Firstly,
      mechanism of steady state MR signals, generated by rf pulses with short
      repetition times, are focused, and described that the steady state signal
      contains echo signals that have different history. Imaging pulse sequence
      utilizing the steady state signals is referred to as Gradient Recalled Echo (GRE)
      sequence. Secondly, in order to give general description for echo train imaging
      sequences, concept of k-space and k-space trajectory is introduced. The concept
      is useful to realize how echo train imaging sequences such as echo planar imaging
      and fast spin echo imaging collect raw data efficiently.

PMID- 9233001
TI  - [New application of MRI by using echo planar imaging].
AB  - EPI (Echo Planar Imaging) can provide human images with an acquisition time of
      less than 100 ms. EPI has received attention as a robust method for several
      applications, such as functional imaging, diffusion imaging, T2 imaging, and
      perfusion imaging. In addition to these, a couple of new EPI applications for
      brain functional imaging have recently been developed. One is spin targeting
      perfusion imaging, EPISTAR or FAIR, and the other is high-speed spectroscopic
      imaging, EPSI. Spin targeting perfusion imaging can detect inflow change alone
      during brain activation, contrast with bold contrast imaging that includes both
      O2 consumption and inflow effect. EPSI reduces signal acquisition time
      drastically. This review describes the recent advances in this field.

PMID- 9233002
TI  - [Technical progress of three dimensional cinematic MR imaging and functional
      images].

PMID- 9233003
TI  - [Technical aspect of clinical spectroscopic imaging and its recent development-
      hardware and software].
AB  - Today's technical status as well as future developments of clinical spectroscopic
      imaging were overviewed in terms of hardware and software aspects. For the
      hardware development, discussion was focused on superconducting magnet with high
      static fields, new probe designs and fast acquisition of spectroscopic imaging.
      Some of the technical limitation was also included. In software, pulse shape
      design for B1 insensitive excitation, selective signal detection utilizing homo-
      and hetero-nuclear coherence transfer, and post processing of acquired data were
      briefly discussed. Especially the processed data is important to extract chemical
      information for the metabolite which can be utilize in the clinical application.
      Some of the proposed methods were summarized for this.

PMID- 9233004
TI  - [Theory and clinical application of functional MRI: 3D-functional brain mapping].
AB  - Functional magnetic resonance imaging (fMRI) was performed using a clinical 1.5 T
      MR scanner. Normal volunteers and patients with several neurological disorders
      were studied with somatosensory stimulation using sponge at right hand and visual
      stimulation using checkerboard pattern. Both fMR images by gradient echo echo
      planar imaging and three dimensional gradient echo images were studied.
      Reconstructed 3 dimensional functional brain mapping was superimposed on 3D
      anatomical images. Apparent signal increase was observed at contra lateral
      sensorimotor cortex and secondary sensory cortex with sponge stimulation. In the
      case of left homonymous hemianopia due to cerebral infarction, increasing signal
      was only observed surrounding left calcarine fissure by using stimulation of all
      visual field. In conclusion, fMRI and 3-D functional brain mapping has extremely
      high potentiality to examine pathophysiology of various neurological disorders.

PMID- 9233005
TI  - [Functional MRI using interleaved EPI].
AB  - One of main purposes of functional MRI is to identify functional map on human
      brain. We considered spatial resolution was a important factor and investigated
      influences of it on signal changes and activated region size. Functional images
      were acquired with Echo-Planar imaging (EPI) and interleaved EPI (IEPI). IEPI is
      superior in spatial resolution but inferior in signal to noise ratio (SNR) to
      EPI. As a result of Student's t-test analysis, activated region sizes of IEPI
      reduced to less than half those of EPI while IEPI had larger signal increase than
      EPI. We confirmed that the reduction was caused by low SNR and our estimation
      analysis could prevent it.

PMID- 9233006
TI  - [Functional MRI of higher brain function with gradient echo on clinical MR unit].
AB  - MR imaging of brain function has been successfully performed at 1.5 T clinical MR
      unit. In the early studies, functional MRI were performed with simple stimulation
      such as visual and motor. Recently, many investigators have attempted to
      demonstrate the specific brain localization of higher brain functions such as
      memory, imagination, language and so on. In this study, we attempted the
      functional MRI for motor and word imagination with gradient echo sequences on
      clinical MR unit. In our experiences, motor cortex was activated on motor
      imagination task and Broca area was activated on word imagination task,
      respectively. We demonstrated the higher brain functions were able to be
      demonstrated on clinical MR unit with gradient echo sequences.

PMID- 9233007
TI  - [Brain functional MRI using 3D-SPGR pulse sequence].
AB  - We reported the effects of motor cortex stimulation of normal volunteers using
      conventional MR imaging techniques on standard 1.5 T clinical scanner. The
      imaging technique was an optimized conventional 2D and 3D spoiled GRASS. In the
      3D-SPGR measurement, a slab of 96 mm with 32 partition was evaluated in sagital
      direction. The motor cortex stimulation was achieved by touching each finger to
      thumb in a sequential, self-paced, and repetitive manner. During stimulation,
      areas of increased signal intensity were identified in the sensorimotor cortex
      with both 2D and 3D SPGR method. The 3D-SPGR method in sagital direction is
      rather insensitive to inflow effects, thus signal increases with 3D-SPGR method
      is mainly due to the blood oxygenation level dependent effects.

PMID- 9233008
TI  - [Motor functional MRI by spiral scan--compared with GRE].
AB  - Recently, functional MRI (fMRI) has been performed in two methods using 1.5 tesla
      machine. One was performed using gradient recalled echo (GRE), the other was
      performed using echo planner imaging (EPI). There is a third method for fMRI
      called spiral scan. This method is applicable without strong gradient magnetic
      field such as required by EPI. In this study, motor fMRI was performed in ten
      normal volunteers by both spiral scan and GRE. Less than 1% risk (t-test), spiral
      scan showed the reactive area more clearly than GRE. And GRE showed higher signal
      intensity changing ratio than spiral scan, but there was no significant
      difference between spiral scan and GRE. The acquisition time of spiral scan was 2
      seconds per image, and that of GRE was 10.5 seconds. Spiral scan has good
      temporal resolution and contrast-noise ratio. These are very advantageous for
      fMRI.

PMID- 9233009
TI  - [Brain functional MRI of the visual cortex with echo planar imaging].
AB  - Brain functional MR imaging (fMRI) is a non invasive imaging method for detecting
      neural activity. We performed functional MRI of the visual cortex with gradient
      echo echo planar imaging (GE-EPI) and spin-echo EPI (SE-EPI) using 1.5T MRI
      system. Visual stimuli was performed with a checkerboard patterns. Magnitude and
      temporal phase of correlation between each pixel's time-course and sine functions
      at the frequency of the stimulus was calculated. In all subjects, the activation
      area in visual cortex obtained from SE-EPI was smaller than that from GE-EPI.
      Temporal phase delay images from both GE-EPI and SE-EPI showed signal spread from
      the primary visual cortex to peripheral supplementary areas. Temporal phase
      analysis is important to discriminate the source of the hemodynamic response to
      neural activation in fMRI.

PMID- 9233010
TI  - [Functional brain mapping in motor task and somatosensory stimulation using echo
      planar MRI].
AB  - Functional brain mapping was performed with a 1.5T clinical MRI apparatus. Single
      shot gradient echo echo-planar imaging (EPI) sequence was employed. Normal
      volunteers were studied with the task of grasping hand or opposition of fingers
      at the frequency of 3 Hz, median nerve electro-stimulation, pure somatosensory
      stimulation by roller for acupuncture. Apparent signal increase was observed at
      contralateral sensorimotor cortex with motor task. Signal changes delayed about 5
      seconds compared with the start and the cessation of the task, which may suggest
      that regional changes of CBF and blood oxygen level in capillary and/or in venule
      lag behind electrical excitation. It was hard to detect the activated area with
      median nerve electro-stimulation. On the other hand, roller stimulation provoked
      distinct activated areas at contralateral sensorimotor cortex. The activated
      areas caused by the roller stimulation and the motor task coincided entirely,
      which suggests the possibility of the intermixed localization of primary areas of
      motor and somatosensory. It was also clearly demonstrated that the activated area
      was broader with quick (3 Hz) and complicated motor task (finger opposition) than
      with slow (1Hz) and simple motor task (hand grasping).

PMID- 9233012
TI  - [Brain structures of reading Japanese words with functional MRI].
AB  - This review examines recent progress in understanding mechanisms involved in
      language related brain functions using functional magnetic resonance imaging
      (fMRI). The main focus is to detect differences in reading processes between the
      ideogram (Japanese kanji) and the phonogram (Indo-European language or Japanese
      kana). Inferior temporal (IT) areas on the language dominant side are involved in
      reading both characters. A plasticity model is introduced to explain the
      different localizations that have been ascribed to kana or kanji, respectively.
      FMRI will be an important clinical application for the preoperative evaluation of
      patients with lesions adjacent to these areas in the near future. Activation
      studies involving visual imagery and other relevant clinical issues are also
      briefly reviewed.

PMID- 9233011
TI  - [Somatotopical mapping of the human somatosensory cortex with echo-planar MRI].
AB  - The somatotopical organization of the somatosensory cortex was analyzed. Echo
      planar imaging was used to obtain functional images, and magnetic field strength
      was 1.5T. Natural stimulation at a frequency of 3 Hz (scrubbing or tapping) was
      applied to one of the three cutaneous areas: toes, fingertips, and tongue tip.
      The focal bands which show the significant signal increases were located on the
      contralateral post-central gyrus, and these changes of signal intensity originate
      from the cortical parenchyma because there were no major veins in the central
      sulcus. The focal bands which respond to each stimulation sites were anatomically
      distinct and located medially-to-laterally in the order of toes, fingertips, and
      tongue tip.

PMID- 9233013
TI  - [Functional MRI in search of basal ganglia].
AB  - We investigated activation of the globus pallidus using conventional gradient
      echo sequence with a 1.5 tesla equipment. In accordance with complex finger
      tapping in the left hand, an increase in signal intensity from bilateral globus
      pallidus was attained, being grossly predominated on right side. On the other
      hand, activations in primary motor cortex were elicited mainly on right side,
      thereby being correctly accorded in attitude of on-off changes in signal
      intensity. fMRI in basal ganglia faces severer condition in detecting real
      activation, owing to influences to signal recording by ventricular pulsation,
      accumulation of iron by age, and differences in activation by the tasks applied.
      This study, however, suggests that fMRI of basal ganglia is a promising technique
      for mapping brain function in regard to correlations between cerebral cortex and
      deep structures.

PMID- 9233015
TI  - [T2*-contrast perfusion study--principles, theory and clinical utility in
      evaluating cerebral hemodynamics].
AB  - Contrast-enhanced dynamic study is easily feasible with a clinical MR system, for
      evaluating cerebral perfusion. A bolus of the paramagnetic contrast agents such
      as Gd-DTPA produces inhomogenity of the regional magnetic field between the
      capillaries and extravascular proton, and causes a decrease of signal intensity
      in the perfused region with T2*-weighted sequences. Echo planar imaging (EPI) is
      suitable for contrast-enhanced dynamic study, because it is markedly susceptible
      and provides high temporal-resolution. Tracer kinetic approaches are used for
      analysis of the dynamic data to acquire various perfusion parameters such as time
      delta R2* curve, rCBF, rCBV and MTT. T2*-weighted contrast-enhanced perfusion
      imaging is useful, especially, for detecting hyperacute ischemia and its
      therapeutic window, and depicting vasculature and ability of the brain tumors.

PMID- 9233016
TI  - [Assessment of cerebral circulation using echo planar imaging--basic analysis in
      quantitating the mean transit time, cerebral blood flow, and cerebral blood
      volume].
AB  - The mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume
      (CBV) using echo planar imaging (EPI) in 22 aged volunteers were measured based
      on moment analysis and gamma variate method. The first peak of signal intensity
      curve (p delta R2.) and the area under the curve after the first peak (AUC) were
      calculated according to the height over area method, as a convenient
      quantification. Then, MTT, CBF, and CBV were compared with AUC/p delta R2, p
      delta R2, and AUC, respectively. There was a good correlation between each other
      parameter (r = 0.67 - 0.92, every p < 0.001). The slow upward slope and the low
      peak height, however, caused a larger error between each other parameter.

PMID- 9233014
TI  - [Functional MRI employing diazepam; a proposal of neuropharmacological fMRI].
AB  - Employing the active benzodiazepine receptor (BZR) ligands, we have used BOLD
      fMRI to elucidate the effects of these drugs on brain function. The sequential
      MRI was performed with a 1.5T clinical scanner (Philips GYROSCAN) using a FLASH
      sequence with the following parameters: TR/TE, 100/45 msec; flip angle, 25
      degrees; matrix size, 128*128; 2 averages; for 64 image acquisitions in 32 min.
      First, 2 mg of diazepam was administrated intravenously at the beginning of the
      5th, 15th, 25th, and 35th acquisitions. Then, flumazenil was administrated at the
      beginning of the 45th (0.2 mg) and 55th (0.3 mg) acquisitions in order to reverse
      the effect of diazepam. Data processing was made employing Akaike Information
      Criterion to detect if there were intensity changes after the medication among
      the trends of intensity changes. Diazepam administration decreased the intensity
      for a while and flumazenil increased one. In the case of the left frontal glioma
      with focal epileptogenicity, intensity changes were detected around the tumor.
      Since the neuronal function consists of the trans-neuronal communications
      employing neurotransmitters, the result on the modulation of this passage depends
      on the neuronal function related to the transmitter: gamma-amino butyric acid
      (GABA) in this instance for the effects of these medications to epilepsy. The
      change in the local blood flow is the result of the local neuronal activity.
      Therefore, we speculate that this neuropharmacological functional MR image may
      reflect the neuronal function related to the GABAegic neurotransmitter system. In
      addition to elucidating basic neurotransmitter function mechanisms, we believe
      this technique may have clinical utility in the pre-surgical evaluation of
      patients with intractable seizure disorders. In this respect, this paper presents
      a new spectrum of fMRI that is capable to study a part of neurotransmitter
      function employing the BZR ligands, reversing the effect of the agonist with the
      competitive antagonist, for the first experience, to propose the
      neuropharmacological functional MR images to have clinical utility in patients
      with intractable epilepsy in the interictal state.

PMID- 9233017
TI  - [Assessment of radiotherapy effects on brain tumors by dynamic susceptibility
      contrast MR imaging].
AB  - Dynamic susceptibility contrast MR imaging(DSC MRI) was performed on eleven
      patients with brain tumors before and after radiotherapy. Their confirmed
      diagnoses were as follows: hemangioendothelioma(n = 1), meningioma(n = 1), low
      grade astrocytoma(n = 1), glioblastoma(n = 2), and brain metastasis(n = 6). The
      purpose of this study is to determine whether this technique is clinically useful
      for monitoring radiotherapeutic effect on brain tumors. Region of interest(ROI)
      analyses were performed on both the brain tumor and the contralateral normal area
      to evaluate the therapeutic effect semiquantitatively. The calculated subtraction
      images, rCBV maps, were also produced for the visual evaluation of the change of
      tumor vascular beds. The results showed that DSC MRI was clinically useful
      because of the capability to offer additional functional information.

PMID- 9233018
TI  - [Assessment of regional microcirculatory changes by EPI perfusion studies in
      patients with multiple lacunar infarction].
AB  - The aim of this report is to assess regional cerebral microcirculatory changes by
      EPI perfusion study in patients with multiple lacunar infarction(MLI).
      Especially, we focused on the parameter(rCBV, MTT, rCBF) changes in the white
      matter and on the relationship between these changes in the gray and white
      matter. Twenty MLI patients(mean age 72 +/- 15 years) and 10 age-similar normal
      controls (mean age 65 +/- 12 years) were examined. As a result, the MLI patients
      demonstrated an insignificant rCBF reduction due to the rCBV elevation in the
      gray matter and a moderate rCBF reduction with less rCBV elevation in the white
      matter. These results show a difference in the vascular reserve between the gray
      and white matter, and insufficiency of the vascular reserve in MLI's white
      matter.

PMID- 9233019
TI  - [Principles and clinical applications of diffusion weighted echo planar MR
      imaging].
AB  - The ultrafast capability of echo planar imaging(EPI) made diffusion-weighted MRI
      (DWI) measurements practical, without the need of head fixation and without the
      need to exclude patients unable to hold still. The DW hyperintensity and reduced
      apparent diffusion coefficient(ADC) were observed in all hyperacute strokes,
      initially at 2.5 hours. In contrast to decreased ADC within 10 days and DW
      hyperintensity within 30 days, ADC was increased without DW hyperintensity in
      chronic stage. This suggests that DWI can discriminate between acute and chronic
      strokes. Furthermore, DWEPI and T2-weighted EPI were also be useful to detect and
      distinguish acute hemorrhagic stroke from nonhemorrhagic stroke. This review
      highlighted the promising technique of DWEPI to examine stroke patients in
      routine clinical practice.

PMID- 9233020
TI  - [Magnetic resonance axonography by diffusion weighted echo planar imaging].
AB  - Anisotropy of apparent diffusivities of water molecules is known to be an
      excellent means for elucidating detailed information regarding neuronal fiber
      direction and density in live subjects. The recent development of magnetic
      resonance axonography (MRX) utilizing three dimensional anisotropy
      contrast(3DAC), using Echo Planar Imaging(EPI), a new algorithm for the treatment
      of apparent diffusion tensor, has provided an unprecedented opportunity for
      visualizing anatomic detail of the human brain. In this study, we applied the
      3DAC method in normal human brain. The results clearly demonstrated that 3DAC is
      highly sensitive to orientation of fiber tracts. Considering the rather simple
      implementational process and high anatomic resolution, MRX based on the 3DAC
      method appears to be the ideal non-invasive imaging technique for assessment of
      the human brain in biomedicine.

PMID- 9233021
TI  - [Measurement of cerebral blood flow using phase-contrast MRI].
AB  - The development of phase-contrast magnetic resonance imaging(P-C MRI) provides a
      noninvasive method for measurement of volumetric blood flow(VFR). The VFR of the
      left and right internal carotid arteries and basilar artery were measured using P
      C MRI, and total cerebral blood flow(tCBF) was calculated by summing up the VFR
      values in three vessels. We investigated the changes in these blood flows as
      influenced from age, head size, height, weight, body surface area and handedness.
      Moreover, regional CBF(rCBF) was measured by combining with the single photon
      emission computed tomography(SPECT) of 123I. The blood flows were 142 +/- 58 mL/
      min(mean +/- SD) in the basilar artery, 229 +/- 86 mL/min in the left, 223 +/- 58
      mL/min in the right internal carotid artery, and tCBF was 617 +/- 128 mL/min(Ref.
      Magn Resn Imaging 14:P. 1143, 1996). Significant increases were observed in head
      size-related change of VFR in the basilar artery and height-related change of
      tCBF. The value of rCBF was easily acquired in combination with SPECT. Phase
      contrast MRI is useful for a noninvasive and rapid analysis of cerebral VFR and
      has potential for clinical use.

PMID- 9233022
TI  - [Detection of pulsated blood flow by cine mode 3D angiography].
AB  - The phase contrast(PC) has an advantage to get an information about flow speed of
      blood along the gradient axis. The cine mode 3D-PC MRA was performed by a 1.5T
      clinical MR system(GE; Signa) using multi-slices gradient echo sequence with ECG
      gating and velocity-encoding gradient along three orthogonal axes. The cine mode
      3D-PC data in three axes was constructed from 10 cardiac phases, respectively.
      The black and white cine mode 3D-PC MRA enabled to get an information of blood
      flow speed. The color MRA, in which flow direction was assigned with RGB colors,
      enabled to observe flow orientation of blood. Furthermore, the flow speed vector
      in each pixel showed a detail flow information in the intravascular space.

PMID- 9233023
TI  - [Evaluation of cerebral ischemia with metabolic image by using 3D-CSI--comparing
      with SPECT and PET].
AB  - MR spectroscopy(MRS) is a powerful method to evaluate brain metabolism directly
      and non-invasively. We developed 3D-CSI method as a multi-voxel MRS. It has some
      advantages or single-voxel MRS; 1) spectra in many voxels can be acquired
      simultaneously 2) Mapping of metabolites can be acquired 3) A small size voxel
      can be obtained. It make it possible to evaluate the change of NAA in wide area.
      In case of cerebral ischemia, we found the tendency that NAA decreases in fatal
      damage area and is normal in recoverable damage area. Therefore, we suppose that
      NAA could be a indicator of viability of neuron. It is necessary to coordinate
      the data from MRI/ MRS and PET/SPECT for analyzing the pathophysiology of
      cerebral ischemia.

PMID- 9233024
TI  - [1H-MRSI of Alzheimer's disease].
AB  - To evaluate neuronal change in the neocortex of the patients with Alzheimer's
      disease in early stage, proton MRSI study was performed in 13 probable AD
      patients and 6 healthy volunteers and the change of NAA, a putative neuronal
      marker, between the temporal cortex and the white matter including basal ganglia
      was analyzed. Proton MRSI data were measured with 3D-FT-CSI method, using spin
      echo method with TE = 135 ms. Two directional 16 x 16 phase encodings were
      applied on the field of 18 x 18 x 1.5 cm3. One voxel size was 1.9 cm3. Out of
      thirteen probable AD patients, 7 patents, who were considered in early stage,
      showed low NAA levels in the temporal neocortex without NAA change in the white
      matter including basal ganglia. Six patients, who were considered in more
      advanced stage, showed low NAA levels in both regions. NAA decrease in
      neocortical area is considered to be a good indication of AD in early stage at
      the examination with proton MRSI.

PMID- 9233025
TI  - [Metabolic imaging of human brain tumors: H-1 chemical shift imaging and PET].
AB  - Positron Emission Tomography(PET) and Proton Chemical Shift Imaging(1H-CSI) has
      provided a cerebral metabolism. The glucose analog fluorine-18 fluorodeoxy
      glucose(FDG) and amino acid analog 11C-L-methionine is the most commonly used PET
      tumor tracer. This time we compare with 1H-CSI and PET in gliomas and metastatic
      brain tumor with computer-assisted fusion images. We experienced some cases of
      the brain tumor. One case is metastatic brain tumor after radiation therapy,
      localized in right parietal hemisphere, with hemorrhage, and slightly accumulated
      Gd-DTPA in tumors. 11C-methionine PET demonstrates defects in tumors, but slight
      accumulated surrounding tumors. Accumulation of PET lesion is not elevated
      choline in CSI, but lactate is accumulated in tumors. Choline signal elevation
      seen in brain neoprasms, associated with increased cellular proliferation.
      Accumulation of PET and another accumulation of lactate in tumor are not
      demonstrate recurrence. Fusion image of PET and CSI is useful in understanding
      metabolism of brain tumor.

PMID- 9233027
TI  - [Clinical application of 31P-chemical shift image using 31P-volume coil to
      Moyamoya disease].
AB  - 31P-MRS and 31P-Chemical Shift Image(CSI) using volume coil were applied to
      Moyamoya disease of 14 cases, data of which were compared with clinical
      manifestations and neuroimagings. In four asymptomatic cases, signal intensity of
      both total P and total ATP was almost equal in each voxel, but in other cases,
      both signal intensity of the lesion was relatively decreased, compared with non
      lesion. Especially, signal intensity of total P and total ATP in ischemic lesion
      was significantly decreased. This showed that 31P-CSI is able to demonstrate
      cerebral ischemic lesion not detected by CT and MRI. We have reported on Moyamoya
      disease that 31P-MRS comparatively correlates to cerebral blood flow and 31P-CSI
      demonstrates ischemic lesion as not detected by CT and MRI less invasively.

PMID- 9233026
TI  - [Mapping of cerebral metabolism on cerebral disorders using multi-slice proton
      magnetic resonance spectroscopic imaging].
AB  - Multi-slice proton magnetic resonance spectroscopic imaging(MRSI) was performed
      using a 1.5 T clinical MR apparatus. Normal volunteer and several kinds of
      cerebral disorders were examined using following parameters; Tr/Te = 2.3 s/280
      ms, slice thickness/gap/slices = 15/3.5 mm/4, 32 phase encoding and 24 cm FOV.
      Every 4 slice images of NAA, Cr, Cho and Lip/Lac were obtained in about 34
      minutes. In control cases, images of Cr and Cho showed very high intensity at
      cerebellum comparing with cerebrum. This means high concentration or changes of
      relaxation times of both Cr and Cho. In cerebral infarction and brain tumor,
      though NAA images showed no signal intensity, Cr and Cho images showed small iso
      or mild high-signal intensity areas. These findings suggest neuronal loss and
      gliosis or tumor growth in the lesions. In conclusion, MRSI has extremely high
      potential to evaluate metabolism of brain and cerebral disorders.

PMID- 9233028
TI  - [Advances in high speed MR imaging for the functional assessment of
      cardiovascular system].
AB  - Advances in high speed MR imaging methods are reviewed in connection with cardiac
      application. In cardiac MR imaging, the temporal relationship between signal
      acquisition and electrocardiogram has been altered with the progress from
      conventional spin-echo imaging to echo planar imaging. Introduction of K-space
      segmentation to electrocardiographic gating technique has realized a breath-hold
      cine MRI. As an example of functional MR imaging of the heart, assessment of left
      ventricular wall motion using turbo-FLASH imaging is presented. The importance of
      MR imaging for the functional assessment of cardiovascular system is increased by
      the recent progress in high speed imaging technique.

PMID- 9233029
TI  - [Myocardial wall motion analysis with phase shift imaging: cine phase contrast
      technique].
AB  - MR imaging can be used to measure proton velocity directly as a phase shift with
      the bipolar gradient method. This method is applied in MR angiography as a phase
      contrast(PC) technique. We attempted to evaluate myocardial motion utilizing the
      PC technique. With the cine PC technique, 16-cardiac phased 3D velocity images of
      the myocardium were obtained. In normal subjects, the myocardial velocity
      throughout the cardiac cycle were changes regular in space as well as in time,
      and there was no inconsistency between the motion directions. Whereas, in cases
      with myocardial infarction, 3D velocity images revealed some regions with zero
      velocity and/or some regions which showed reverse direction motions compared with
      the surrounding normal myocardium.

PMID- 9233030
TI  - [Assessment of ventricular wall motion and volume by fast cine MRI using Fastcard
      sequence].
AB  - Left ventricular wall motion and volume are important factors for assessment of
      cardiac function. Recent advances in magnetic resonance imaging(MRI) have allowed
      fast cine MR sequences. Fastcard sequence is an electrocardiographically
      triggered gradient echo sequence with k-space segmentation and have enabled fast
      cine acquisition of the heart during breath holding. Improvement in image quality
      and contrast between myocardium and intraventricular cavity may facilitate
      assessment of cardiac function using the phased array coil. Drug stress MRI for
      detection of significant coronary artery stenosis could be more easily performed
      by this sequence than conventional cine MR sequences. Sequential short axis
      images obtained with Fastcard sequence also provide an accurate method without
      assumption of ventricular shape.

PMID- 9233031
TI  - [Evaluation of left ventricular systolic function using cine MRI--application to
      hypertrophic cardiomyopathy].
AB  - Cine MRI is a useful means to analyse the anatomical and functional changes of
      hypertrophic cardiomyopathy. The visual evaluation of hypertrophic regions and
      the motion patterns of their walls is in most cases possible on cine MR images.
      To complement a subjective method a certain quantitative analysis is necessary.
      Left ventricular regional systolic function can be quantitatively evaluated using
      cine MRI images printed on films. There is a good correlation between % thickness
      of LV wall and its thickness at end diastolic phase. The comparison of %
      thickness of normal subjects with that of hypertrophic cardiomyopathies shows a
      tendency of its value being less at the region of more severe hypertrophic
      change.

PMID- 9233032
TI  - [Estimation of left ventricular wall motion and viability by SPAMM tagging cine
      MRI].
AB  - To estimate the endocardial and epicardial myocardial function separately in
      patients with myocardial infarction patients with or without reperfusion therapy,
      the magnetic resonance imaging with tagging by spatial modulation of
      magnetization (SPAMM) was utilized and the endocardial and epicardial early
      diastolic strains were evaluated separately. The strain changes were correlated
      with the thallium-201 uptake and a good correlation between epicardial stain
      change and the thallium-201 uptake was observed. These results indicate the
      specific usefulness of SPAMM tagging in estimating the regional myocardial
      function and viability in reperfused myocardium.

PMID- 9233033
TI  - [Assessment of myocardial perfusion hemodynamics using echo planar MR imaging].
AB  - It was possible to obtain images for individual heart beats using single-shot
      Echo Planar Imaging(EPI), and changes of myocardial signal intensity could be
      assessed visually after GD-DTPA administration. Measurement of the same site in
      the myocardium on myocardial perfusion images for individual heart beats was
      facilitated by imaging during breath-holding, and accurate evaluation was
      possible. In patients with coronary artery disease, the site of myocardial
      infarction tended to show less increase in signal intensity than the normal
      myocardium, and could easily be distinguished from normal myocardium according to
      the change in signal intensity. In patients with atrial fibrillation, the signal
      intensity of the myocardium varied with each heart beat, and it was difficult to
      assess perfusion hemodynamics. Myocardial perfusion studies using EPI still
      present problems with respect to spatial resolution, but the myocardial perfusion
      hemodynamics for individual heart beats can be determined by preparing
      time/intensity curves. It is also possible to obtain information on cardiac
      morphology, wall motion, and myocardial metabolism in addition to perfusion data
      by combining myocardial perfusion studies with methods such as high speed cine
      MRI, tagging, or myocardial MRS. It is possible that this method will also be
      useful in studying myocardial viability.

PMID- 9233034
TI  - [Evaluation of myocardial ischemia with echo planar magnetic resonance imaging
      (EPI): normal and ischemic heart].
AB  - We investigated the validity of Gradient recalled EPI(GRE-EPI) after bolus
      injection of contrast agent(Gadolinium 0.1 mmol/kg) to detect the ischemic zone
      of myocardium. Seven healthy volunteers and fifteen patients with coronary artery
      disease who had only one vessel disease more than 99% stenosis in AHA/ACC
      classification were studied. GRE-EPI was performed in a transaxial, long axis or
      short axis orientation of the left ventricle on a 1.5-T Signa Horizon Scanner.
      Images were obtained every heartbeat for 200 consecutive heartbeats. Contrast
      agent was injected into the antecubital vein in a bolus after 10 heartbeats.
      Signal intensity changes in the left ventricular blood and myocardium were
      measured during myocardial contrast perfusion study. In all healthy volunteers,
      signal intensity in myocardium was reduced by contrast agent following signal
      loss in the left ventricular blood and recovered with wash out of contrast agent.
      But in patients, reduction and recovery of signal intensity in the ischemic zone
      by contrast agent were significantly delayed and much less than that in the
      nonischemic zone. In conclusion, myocardial perfusion imaging with GRE-EPI was
      useful in evaluation of ischemic heart disease.

PMID- 9233035
TI  - [The measurement of the coronary flow by the phase contrast method (cine PC,
      Fastcard PC)].
AB  - We confirmed the accuracy of flow velocity measured by two kinds of phase
      contrast (PC) sequence. The fast PC sequence(FCARDPC) showed a little different
      value from the conventional PC, but the linear correlation was found between
      established values of the instrument and the measured velocity by the fast PC.
      The flow velocity of the right and left coronary arteries in one cardiac cycle
      was measured using two PC sequences on the same subject. It was found that the
      flow velocity in one cardiac cycle was almost the same pattern between the two
      method, though the absolute values of each other differed slightly. We considered
      that the comparison in the same sequence would be acceptable even in clinical
      cases unless the values measured by a different sequence or modality were
      compared directly. Though our experience on diseases are still preliminary, we
      suggest that myocardial ischemia and dysfunction will be related with not only
      the decrease of velocity but also the change of flow pattern of the coronary
      artery in one cardiac cycle. We believe that this method has a potential becoming
      one of the routine methods for evaluating cardiac functions.

PMID- 9233036
TI  - [Assessment of coronary flow reserve using fast phase contrast cine MR imaging].
AB  - Physiological significance of coronary artery stenosis can be evaluated by
      measuring coronary flow reserve(CFR). Segmented k-space cine phase-contrast(PC)
      MR method has been used for measuring coronary blood flow and CFR. MR measurement
      of the CFR ratio(1.62 +/- 0.50, n = 10) in patients with coronary arterial
      stenosis was significantly lower than that measured in healthy subjects(3.14 +/-
      0.59, n = 10, p < .01). The CFR measured by MRI demonstrated a good linear
      correlation with the CFR directly measured by Doppler flow wire during X-ray
      angiography(r = 0.91, n = 19). MR measurement of flow volume in the coronary
      sinus and myocardial mass can provide evaluation of blood flow rate per
      myocardial mass for the entire left ventricle, which was substantially decreased
      in patients with hypertrophic cardiomyopathy.

PMID- 9233037
TI  - [Clinical efficacy of three-dimensional chemical shift imaging (3D-CSI)--a study
      of 3D-CSI in the human heart and its clinical perspectives for the future].
AB  - The main purpose of this study was to investigate whether in vivo 31P three
      dimensional chemical shift imaging(3D-CSI) of the human heart could serve as a
      useful tool for evaluating myocardial metabolism. We performed slice-selective 3D
      CSI employing nuclear magnetic resonance(NMR) imaging with slice selection in one
      dimension and phase encoding in two dimensions. 31P NMR images of phosphocreatine
      (PCr) and ATP were superimposed on a corresponding 1H image of the heart. Our
      study revealed that while accurate in vivo 31P 3D-CSI measurement of the human
      heart is difficult to achieve it is not impossible, although various additional
      techniques for improving signal to noise ratio are indicated.

PMID- 9233038
TI  - [Study on Mato cells (Mato's FGP cells) under various conditions].
AB  - Mato cells are unique macrophagic cells locating in the Virchow-Robin space of
      cerebral microvessels. They play a significant role in blood brain barrier, and
      uptake and digest proteinous and lipoidal materials derived from surroundings.
      They are provided with epitopes of macrophage lineages such as MHC Class II and
      scavenger receptor. Under pathological conditions, -cerebral injury,
      hypercholesteremia, hypertension and congenital dysfunction of nerve and some
      enzymes-induce heavy damages of Mato cells in shape and contents, and some of
      Mato cells are going into degeneration. Subsequently, the architecture of
      microvessels is also modified and result in the narrowing of vascular luminae.
      Finally, the authors discusses these findings referring to the earlier reports of
      Alzheimer (1913).

PMID- 9233039
TI  - [Gene therapy for brain tumors].
AB  - Patients with glioma(which constitute 33% of all brain tumor cases) still have a
      poor prognosis, especially in the case of malignant(anaplastic astrocytoma and
      glioblastoma). This poor prognosis is related to the fact that malignant glioma
      cells aggressively infiltrate into normal brain tissues, making total removal of
      the tumor impossible. The median survival time of glioblastoma patients is less
      than 2 years, despite multimodality treatment with extensive surgical resection
      and adjuvant therapies using radiation and immunochemotherapy. In order to
      overcome this formidable neoplasm, the effectiveness of molecular neurosurgery
      using gene therapy has been investigated since 1992. In this paper, the current
      state of gene therapy for malignant brain tumors are described, and the future
      direction of this fascinating approach is discussed.

PMID- 9233040
TI  - Clinical usefulness of autologous transfusion--history, methodologies and
      problems with popularization.
AB  - Autologous transfusion(AT), using the patient's own blood for replacement during
      operation, is the most useful blood replacement method, as the blood is a perfect
      match for the patient. It can prevent alloimmunization and introduced viral
      infections completely. Predeposition, Hemodilution and Salvage are the three
      methods of collection. Each has already had sophisticated techniques developed
      for clinical application. Unfortunately, AT requires extensive man-power and is
      expensive. For these reasons, AT has been slow to gain popularity in the surgical
      field in Japan. For popularization of AT to be successful, not only must we have
      sufficient knowledge to implement these complicated techniques, but we must also
      build an AT center staffed by several specialists in each hospital.

PMID- 9233041
TI  - The status of emergency medical services in North Carolina.

PMID- 9233042
TI  - The North Carolina Trauma System.

PMID- 9233043
TI  - Disaster response in North Carolina.

PMID- 9233044
TI  - Air medical transport services in North Carolina.
AB  - Air medical transport is an important component of contemporary prehospital care
      for patients with time-sensitive conditions and those whose clinical needs exceed
      the expertise of local providers. Early contact with trained flight dispatchers
      facilitates air transport. Appropriate stabilization, effective communication,
      and transfer of medical documents ensure that transports are appropriate, timely,
      and safe.

PMID- 9233045
TI  - Managed care authorization for emergency department services. A medical risk to
      patients, a legal risk for doctors and hospitals.

PMID- 9233046
TI  - Children--media violence--solutions.

PMID- 9233047
TI  - Poison control in North Carolina.
AB  - Poison centers contribute importantly to public health. They provide expert
      emergency advice without charge, offer early telephone triage of poisoning cases,
      assist parents and caretakers in managing simple exposures at home, and
      recommended hospital evaluation for patients suspected of serious exposure. Their
      efforts lead to significant cost savings by averting unnecessary medical
      evaluations. Poison centers offer physicians and other clinicians consultation
      with board-certified medical toxicologists to arrange for definitive care or,
      more often, to help provide good, cost-effective care in local communities. The
      Poison Center's efforts to prevent accidental poisoning and to increase awareness
      and utilization of its services benefit both patients and health care providers
      by reducing morbidity and costs associated with poisonings.

PMID- 9233048
TI  - Injury prevention and control. An evolving role for emergency physicians and
      other specialists.

PMID- 9233050
TI  - The history and future of emergency medicine.

PMID- 9233049
TI  - Injuries associated with personal watercraft. An emerging epidemic in need of
      legislative action.

PMID- 9233051
TI  - Emergency medical services for North Carolina's children.

PMID- 9233052
TI  - Research in emergency medicine.

PMID- 9233053
TI  - Effects of sumatriptan on growth hormone releasing hormone-stimulated growth
      hormone secretion in acromegaly.
AB  - Sumatriptan (SU), a specific 5-HT1D receptor agonist, was recently shown to be
      able to increase growth hormone (GH) levels in normals, but not in acromegalics,
      while no effect was seen on prolactine (PRL). SU is also able to produce an
      increase in GH response to growth hormone releasing hormone (GHRH) in prepubertal
      children. In this study we investigated whether SU administration influences GHRH
      induced GH secretion in 8 acromegalics, and 6 age-matched normal volunteers, as a
      control group. We evaluated the effects of SU (6 mg s.c.) or placebo (PL)
      administration on GHRH (1 microgram/kg bw i.v.)-induced GH and PRL secretion.
      After SU priming the GH response to GHRH did not changed in acromegalics, but
      significantly decreased in controls, in comparison with that observed after PL
      plus GHRH. In acromegalics, no difference in GH peak was seen after SU plus GHRH
      and PL plus GHRH, nor was any difference seen in AUC between tests. In controls,
      no difference was seen in GH peaks, while SU priming significantly (P < 0.03)
      decreased the AUC 90-120 min of GH after GHRH administration. In acromegalics, SU
      did not change the slight GHRH-induced increase in PRL levels. Our study
      documents that 5-HT1 D receptors do not interfere with GHRH-stimulated GH
      secretion in acromegalic subjects. In normals, SU is able to decrease GH response
      to GHRH, thus confirming that 5-HT1D receptors are able to modulate GH secretion
      in normals.

PMID- 9233055
TI  - The World Health report 1996--fighting disease, fostering development.
AB  - This self-contained, concise and analytical publication is the second in a new
      series of annual reports. It provides an annual assessment of world health status
      and needs, and recommends relevant priorities for international health action to
      meet those needs, as well as reporting on WHO's contribution towards improving
      the world health situation. The world health report 1996 focuses on infectious
      diseases and gives an overview of WHO's work during 1995 (1).

PMID- 9233054
TI  - Ischemic optic neuritis in Churg-Strauss syndrome.
AB  - There are few reports of neuro-ophthalmologic involvement in Churg-Strauss
      syndrome (CSs). We described a case of unilateral optic atrophy in a 46-year-old
      white man with CSs. The patient had severe bronchial asthma, allergic rhinitis,
      hypereosinophilia (8%) and peripheral neuropathy. The visual acuity in his right
      eye was light perception. At the biomicroscopy there were no corneal and
      conjunctival lesions. Ophthalmoscopy showed a pale right optic disc and
      fluorangiography revealed a marked hypofluorescence of the disc at early phase of
      angiogram. We suggested that the optic atrophy was most probably due to
      vasculitis of the ciliary arteries.

PMID- 9233056
TI  - Health dilemmas at the borders--a global challenge.
AB  - The health and safety of border crossers and people who live in border areas are
      widely neglected. The remoteness of many communities living near international
      borders makes it difficult to provide them with services, and if a country's
      border controls are inadequate there is an increased risk from communicable
      diseases for its entire population. Substance abuse and associated behavioural
      problems can be more common in border regions for the same reason. Armed
      conflicts, economic pressures and natural disasters can precipitate the movement
      of refugees across borders and the disruption of local infrastructures.
      Environmental hazards tend to be heightened in border regions because of the
      dumping of waste, the pollution of the atmosphere by slow-moving vehicles, and
      the contamination of water by sewage. Furthermore, dangers may arise because of
      unsafe implementation of trade agreements and the movement of uregulated
      materials. There is an urgent need for health education and the promotion of
      family and individual health care in many border regions. A global initiative on
      health and safety at international borders is clearly needed. It should include
      needs assessment, new policies and action programmes.

PMID- 9233057
TI  - Success against lymphatic filariasis.
AB  - A campaign against lymphatic filariasis began in China's Shandong Province during
      1956. Epidemiological surveillance since 1984 indicates that the transmission of
      infection has been interrupted. The factors accounting for this are discussed and
      the continuing challenges presented by the disease are outlined.

PMID- 9233058
TI  - Malnutrition, malaria and intestinal worms in young children.
AB  - A study is reported from two indonesian villages on the prevalence of
      malnutrition, malaria and intestinal worms among children aged 6-17 months.
      Malnutrition, insofar as it is reflected by blood haemoglobin levels, was the
      most widespread problem and was evidently caused by food shortages and
      unsatisfactory traditional feeding practices rather than by disease or other
      environmental risk factors.

PMID- 9233059
TI  - Integrated community-based screening for cardiovascular diseases of childhood.
AB  - A screening programme in northern India, principally aimed at detecting and
      controlling rheumatic fever and rheumatic heart disease (RF/RHD) in children,
      also picks up individuals with congenital heart disease and other cardiovascular
      conditions, who are then referred for consultation and treatment. This strategy
      is clearly more ethical and cost-effective than screening programmes concerned
      exclusively with the control of RF/RHD.

PMID- 9233060
TI  - Oral health education for medical students.
AB  - With a view to improving oral health in Oman, particularly in the interior of the
      country where dental services are very scarce, medical students have been
      receiving a grounding in this field since 1988. The results achieved so far have
      proved encouraging.

PMID- 9233061
TI  - Making health messages interesting.
AB  - In Afghanistan a radio drama serial carrying messages vital to the well-being of
      the population, backed up by more detailed information in reinforcing radio
      programmes and a cartoon magazine, is proving effective in increasing people's
      knowledge of immunization and other subjects.

PMID- 9233063
TI  - Safe air in the workplace?

PMID- 9233062
TI  - Mosques against malaria.
AB  - In a community-based malaria control project covering a predominantly Muslim
      population in the United Republic of Tanzania, difficulty was encountered in
      motivating people to have their mosquito nets reimpregnated with insecticide at
      six-monthly intervals. Education on this subject was therefore provided in
      mosques during Friday noon prayers. People who attended these services considered
      them an appropriate forum for discussing health concerns and viewed them as a
      credible source of information.

PMID- 9233064
TI  - Water: where from, and for whom?
AB  - When the agricultural sector takes measures to diminish water losses, access to
      water for domestic purposes may be greatly reduced and community health may be
      adversely affected.

PMID- 9233065
TI  - Challenges in health development.
AB  - Health development projects in Bolivia and Zimbabwe are described in order to
      illustrate that, in economically depressed areas, the integration of services
      within the health sector alone is not sufficient to obtain the desired results.
      Significant barriers to sustainable progress are inevitable unless there is
      functional coordination with other sectors.

PMID- 9233066
TI  - Hospitals in Latin America and the Caribbean.
AB  - Health services provided by public or private institutions at the primary and
      hospital referral levels should be coordinated so that the available resources
      are distributed equitably to meet the needs and aspirations of the population.
      The challenge is to improve the quality of hospital care and the existing pattern
      of public and private services in Latin America and the Caribbean.

PMID- 9233067
TI  - "Action research" in health programmes.

PMID- 9233068
TI  - Integrated medicine--many approaches, one service.
AB  - The bringing together of different medical systems offers the prospect of an
      increase in the quality of care and improved cost-effectiveness. This is
      discussed with particular reference to initiatives being taken in India.

PMID- 9233069
TI  - One person, two roles: nurse and traditional healer.
AB  - In South Africa it is intended that health care should become more community
      driven. One requirement for achieving this is to bring together the traditional
      and modern medical systems. Nurse/traditional healers, being involved in both
      systems, can contribute significantly to increased collaboration and
      understanding between them provided that restrictions on their activities in
      hospitals are diminished.

PMID- 9233070
TI  - Medical and professional negligence.

PMID- 9233071
TI  - Community-based health insurance.

PMID- 9233072
TI  - Difficulties of putting dietary changes into practice.

PMID- 9233073
TI  - Rapid appraisal before impact evaluation studies.

PMID- 9233074
TI  - Underutilization of maternal health services.

PMID- 9233075
TI  - Baby-friendly hospitals in Kerala.

PMID- 9233076
TI  - Fluoride content of drinking-water and beverages in Jordan.

PMID- 9233077
TI  - Drug delivery and health workers' behaviour.

PMID- 9233078
TI  - Too many vitamins for diabetics.
AB  - A study in Alkhobar, Saudi Arabia, indicates that multivitamins are commonly
      prescribed on a routine basis for patients with diabetes mellitus. There is no
      scientific justification for this practice, which unnecessarily increases the
      cost of care, and doctors should be advised against it.

PMID- 9233079
TI  - Oral rehydration at home--with a little help from friends.
AB  - A training workshop was organized for selected members of two village populations
      in north-eastern Nigeria, whereby they acquired knowledge and skills enabling
      them to spread the word and practice of oral rehydration therapy for children
      suffering from diarrhoea in their communities. The difficulties encountered and
      the gains achieved in this empowerment programme are described below.

PMID- 9233080
TI  - Reproductive tract infections--and associated difficulties.
AB  - In addition to financial constraints there are significant social, educational,
      moral and religious barriers to the prevention and treatment of reproductive
      tract infections in rural India. A pilot project aimed at achieving progress in
      this field is reported below.

PMID- 9233081
TI  - What action for rational drug use?
AB  - The author reviews the use of medicinal drugs in Pakistan and suggests measures
      for improving the present situation. Particular attention is given to the
      selection, availability and rational use of essential drugs. Reference is also
      made to procurement policy, quality control, drug registration and control, the
      education of doctors and pharmacists, the dissemination of drug information,
      prescribing practices, and the availability of prescription drugs without
      prescription.

PMID- 9233082
TI  - Syntactic categorization in early language acquisition: formalizing the role of
      distributional analysis.
AB  - We propose an explicit, incremental strategy by which children could group words
      with similar syntactic privileges into discrete, unlabeled categories. This
      strategy, which can discover lexical ambiguity, is based in part on a
      generalization of the idea of sentential minimal pairs. As a result, it makes
      minimal assumptions about the availability of syntactic knowledge at the onset of
      categorization. Although the proposed strategy is distributional, it can make use
      of categorization cues from other domains, including semantics and phonology.
      Computer simulations show that this strategy is effective at categorizing words
      in both artificial-language samples and transcripts of naturally-occurring, child
      directed speech. Further, the simulations show that the proposed strategy
      performs even better when supplied with semantic information about concrete
      nouns. Implications for theories of categorization are discussed.

PMID- 9233083
TI  - How important are rhyme and analogy in beginning reading?
AB  - Current debate over the influence of phonological awareness on early reading
      development is polarised around small-unit (phoneme) processing and large-unit
      (onset-rime) processing. These opposing theories were contrasted by assessing the
      impact of pre-school phonological skills on reading amongst children experiencing
      their first year of formal instruction by a mixed method. Those beginning readers
      who could decode nonwords were found to have accomplished this by employing their
      letter-sound knowledge rather than by making analogies based on familiar rime
      units. Children displayed this pattern of performance regardless of their pre
      school rhyming skills. Further investigations revealed that explicit awareness of
      onset and rime units was poor, even amongst children whose implicit rhyming
      skills were excellent. This evidence, together with the children's knowledge of
      orthographic units, was consistent with the view that letter-sound
      correspondences rather than onset or rime units formed the basis of their first
      attempts to utilise phonology in reading. The findings are discussed with
      reference to instructional influences on early reading and phonological
      awareness.

PMID- 9233084
TI  - Detecting high-level and low-level properties in visual images and visual
      percepts.
AB  - In this article we provide further evidence that visual mental imagery and visual
      perception share modality-specific mechanisms, and we find that representing
      visual information in a mental image (activating stored information to create a
      picture-like mental representation) preserves relatively low-level visual detail.
      Subjects either saw or visualized simple pictures, and evaluated them for the
      presence or absence of six types of non-accidental properties. These properties
      varied from very 'low-level' ones, such as T junctions, to very 'high-level'
      ones, such as global symmetry. The question was whether both sorts of information
      are equally accessible in percepts and mental images. If mental images are
      equivalent to descriptions of perceptual units and their organization, as some
      have argued, then subjects should have greater difficulty accessing low-level
      properties in a mental image compared to the difficulty they experience when the
      drawing is visible. The results of two experiments were clearcut: Subjects could
      evaluate high-level properties more easily than low-level ones, but this
      difference was the same in imagery and perception. These findings suggest that
      mental images preserve relatively low-level visual features, and are not simply
      descriptions of a pattern.

PMID- 9233085
TI  - Teleological reasoning in infancy: the infant's naive theory of rational action.
      A reply to Premack and Premack.
AB  - We argue that Premack and Premack's criticism of our demonstration (Gergely et
      al., 1995) of interpreting goal-directed action in one year-olds in terms of the
      principle of rationality are ill-founded, and their suggested alternative test
      for goal-attribution is open to lower level interpretations. We show that the
      alterative model they propose for our data in terms of 'appropriate' change of
      means action is but a somewhat imprecise restatement of our account of the
      infant's naive theory of rational action. Finally, we elaborate and clarify our
      model of the teleological stance in infancy which we suggest is an as yet
      nonmentalistic precursor of the young child's later emerging causal theory of
      mind.

PMID- 9233086
TI  - Motor competence as integral to attribution of goal.

PMID- 9233087
TI  - Reintubation--what is the "gold" standard?

PMID- 9233089
TI  - The nature of supervision.

PMID- 9233088
TI  - Contaminated sevoflurane.

PMID- 9233090
TI  - Nurse anesthesia and religious sisters: Sister Secundina Mindrup.

PMID- 9233091
TI  - Managed care reform in the 105th Congress.

PMID- 9233092
TI  - Credentialing of CRNAs--time for a new look.

PMID- 9233093
TI  - Incidence of visible and occult blood on laryngoscope blades and handles.
AB  - Anesthesia providers must take appropriate precautions to reduce the potential
      for transmission of infectious agents to the patients under their care. The
      devastating spread of human immunodeficiency virus (HIV) and hepatitis B virus
      (HBV) over the past decade has resulted in the development of specific guidelines
      for the cleaning, disinfection, sterilization, and handling of medical equipment
      and instruments. Contamination of laryngoscope blades and handles with visible
      and occult blood frequently occurs during routine airway management. Several
      studies suggest procedures for cleaning, disinfection, sterilization, or handling
      of laryngoscope blades and handles are ineffective, or there may be poor
      compliance with the established protocols. The purpose of this study was to
      determine the incidence of visible and occult blood on laryngoscope blades and
      handles that were identified as ready for patient use. Sixty-five laryngoscope
      blades and handles identified as ready for patient use were observed for visible
      blood and tested for occult blood. A modified version of the three-stage
      phenolphthalein blood indicator test was employed to determine the presence of
      occult blood. None of the blades or handles observed had visible blood. Of the 65
      blades tested for occult blood, 13 (20%) tested positive. Of the 65 handles
      tested for occult blood, 26 (40%) tested positive. More afternoon blades and
      handles tested positive for occult blood than morning blades and handles (P <
      0.01). The extent to which contaminated anesthesia equipment plays in nosocomial
      infection is difficult to determine. The presence of blood is an indicator of
      potential cross-infection, since biological fluids, such as blood and saliva, are
      known to transmit infectious diseases. This study confirms that more rigorous
      decontamination protocols must be instituted to ensure complete removal of blood
      prior to sterilization, since laryngoscope blades and handles have irregular
      surfaces with repositories for infectious material.

PMID- 9233094
TI  - Suspected malignant hyperthermia in a 13-month-old: today's "typical" episode--a
      case report.
AB  - A case of suspected malignant hyperthermia in a 13-month-old female, to whom
      succinylcholine was not administered, is presented. The patient presented for a
      repair of the right radial nerve under general anesthesia. Induction was
      accomplished with halothane, nitrous oxide, and oxygen. Tracheal intubation was
      facilitated with intravenous vecuronium. Controlled ventilation was initiated,
      and anesthesia was maintained with isoflurane, nitrous oxide, oxygen, morphine
      sulfate, and vecuronium. At the conclusion of the surgical procedure, an abrupt
      increase in ETCO2, an elevation in body temperature, and a mixed acidosis was
      observed. Resolution of symptoms followed the administration of dantrolene
      sodium. The patient underwent an uneventful postoperative recovery and was
      discharged home. It was felt that the patient was too young to undergo a muscle
      biopsy for a caffeine-halothane stimulation test.

PMID- 9233095
TI  - Frustrated wants and entitlements: fundamental components of CRNA job
      satisfaction.
AB  - A comparative study was conducted examining CRNA feelings of deprivation or
      resentment as they relate to their job satisfaction. Deprivation is described in
      Faye Crosby's Theory of Relative Deprivation (1976), which posits that six
      psychological preconditions (wanting, comparison other, deserving, past
      expectations, future expectations, and lack of self-blame) have an impact on
      individual perceptions and can influence job satisfaction. Relative deprivation
      is defined as a sense of grievance or feeling of resentment that one has been
      unjustly deprived of some desired thing. It is also sometimes referred to as the
      discrepancy between one's legitimate expectations and one's actual situation. The
      three hypotheses examined compare the influence of the six Crosby preconditions
      of relative deprivation and the three background variables of gender, education,
      and individual job autonomy on CRNA-felt deprivation. Results from three-way
      analysis of variance indicated that of the three background variables, only
      degree of autonomy was found to be significant in explaining felt deprivation.
      That is, irrespective of gender or educational level, CRNAs reporting higher
      degrees of job autonomy had lower feelings of deprivation or resentment about
      their jobs than did individuals reporting limited job autonomy. Degree of
      autonomy, thus being the key background determinant of CRNA-felt deprivation (F =
      14.609, P < .01). Further analysis employing multiple regression revealed that
      when both the background and the Crosby psychological variables were examined
      together, the explained variance in deprivation was dramatically increased by the
      psychological variables far in excess of the background variables. The two
      psychological variables of wanting and deserving were found as most significant
      in explaining CRNA felt deprivation. Results indicate the importance of CRNA
      frustrated wants (wanting) and CRNA perceived entitlements (deserving) as key
      factors contributing to CRNA job satisfaction above and beyond the three
      background variables studied.

PMID- 9233096
TI  - Comparison of axillary block techniques: is there a difference in success rates?
AB  - This study compared the success rates between two accepted methods of performing
      axillary blocks, the peripheral nerve stimulator (PNS) and the transarterial (TA)
      techniques. Success was based on blocking the nerves involved in the surgery.
      Following institutional review board approval and informed consent, 57 patients
      between the ages of 18 and 86 years of age scheduled for elective upper extremity
      surgery were studied. Patients were randomized and all blocks were performed
      according to the protocol for PNS and TA techniques using the dosage of local
      anesthetic based on patient weight. All patients were premedicated with fentanyl
      hydrochloride, 1 microgram/kg, and midazolam, 1 to 5 mg. Scoring was accomplished
      on a standardized form by one of two physicians, unaware of the technique, for 5
      of the major nerves at 20 and 30 minutes after injection. Sensory blockade was
      determined by pinprick. Motor blockade was assessed according to a scale ranging
      from complete block to no effect. Two of the patients had vascular procedures,
      and the remainder were orthopedic procedures. There were no differences in the
      effectiveness on the musculocutaneous, radial, median, or ulnar nerves. There was
      a significant difference (P < 0.05) in the effectiveness at the axillary nerve.
      The transarterial technique was 66% effective as opposed to 47% for the PNS.
      There was no difference in the need for local supplementation or general
      anesthesia between the two groups. There were no significant side effects
      reported by the patients postoperatively. The axillary nerve was the only nerve
      with an increased success rate using the TA technique. This indicates that both
      techniques are equally acceptable.

PMID- 9233097
TI  - Recovery times from subarachnoid blocks using bupivacaine hydrochloride and
      tetracaine hydrochloride with and without epinephrine.
AB  - This retrospective study examined the length of time patients spent in the
      postanesthesia care unit (PACU) recovering from a subarachnoid block with either
      bupivacaine hydrochloride or tetracaine hydrochloride with and without
      epinephrine after total knee replacement surgery or total hip replacement
      surgery. One hundred subjects' charts were reviewed with 50 subjects receiving a
      subarachnoid block with bupivacaine (25 had epinephrine added to the bupivacaine)
      and 50 subjects receiving a subarachnoid block with tetracaine (25 had
      epinephrine added to the tetracaine). There were no statistical differences among
      the groups with respect to age, height, weight, dose of local anesthetic, and
      length of surgical procedure. Patient who received tetracaine stayed longer in
      the PACU (64.44 minutes) and took longer to bend their knees (73.17 minutes),
      flex their hips (99.65 minutes), and have return of sensation (68.88 minutes),
      compared to those who had received bupivacaine (P < .05). When epinephrine was
      added to the local anesthetic, it prolonged the time until the return of knee
      flexion, hip flexion, and sensation by 66.82, 87.65, and 76.77 minutes
      respectively (P < .05).

PMID- 9233098
TI  - Update on carcinoid syndrome.
AB  - The carcinoid syndrome is a result of the release of multiple carcinoid tumor
      factors, particularly serotonin, kinins, and histamine. These factors cause
      flushing, hemodynamic instability, right-sided heart disease, bronchospasm, and
      gastrointestinal symptoms. A through preoperative assessment concentrating on
      these areas is necessary. The use of invasive monitors perioperatively, with the
      avoidance of drugs and techniques that can exacerbate the syndrome, is
      beneficial. Octreotide, both prophylactically and acutely, provides the best
      medical therapy available.

PMID- 9233100
TI  - Leadership--the courage to care.

PMID- 9233099
TI  - AANA journal course: update for nurse anesthetists--serotonin agonists and
      antagonists: anesthetic implications.
AB  - A number of important new pharmacologic agents in widespread clinical use share
      the ability of manipulate serotonin as their mechanism of action. Drugs as
      diverse as the antidepressants fluoxetine (Prozac), sertraline (Zoloft),
      paroxetine (Paxil), and venlafaxine (Effexor); the antimigraine agent sumatriptan
      (Imitrex); the antiobesity agent dexfenfluramine (Redux); and the antiemetics
      ondansetron (Zofran) and granisetron (Kytril) are routinely encountered in the
      perioperative patient. A thorough understanding of the pharmacology, physiologic
      effects, significant drug interactions and anesthetic implications of serotonin
      agonists or antagonists is vital for proper anesthetic management of patients
      receiving these drugs.

PMID- 9233101
TI  - "Anesthesia providers, patient outcomes, and costs": the AANA responds to the
      Abenstein and Warner article in the June 1996 Anesthesia and Analgesia.

PMID- 9233102
TI  - Anesthetic considerations for the new antiobesity medications.

PMID- 9233103
TI  - Double standards in anesthesia.

PMID- 9233104
TI  - Similarities and differences in U.S. nurse anesthesia curriculum and Mexican
      military nurses in anesthesiology curriculum.

PMID- 9233105
TI  - AANA Journal Course: update for nurse anesthetists-brain death: terminology,
      clinical criteria, and diagnostic testing.
AB  - Developmental strides in biomedical technology and the growth and availability of
      intensive care units have paralleled the development of organ transplantation
      programs. The establishment of these programs required the development of a new
      definition, criteria, and test of death to facilitate the procurement of suitable
      organs. The historical definition of death, in instances of organ
      transplantation, is no longer compatible as cardiopulmonary support can be
      readily applied to individuals without spontaneous circulation and respiration.
      This AANA Journal course will examine the definitions of death and the evolution
      of the term "brain death." The essential clinical criteria and confirmatory
      diagnostic testing for the determination of adult "whole-brain death" will be
      reviewed.

PMID- 9233106
TI  - Sevoflurane use in Veterans Affairs medical centers: utility, safety, and cost
      effectiveness.
AB  - It has long been realized that the Veterans Affairs (VA) patient has a high
      incidence of multiorgan system diseases, especially diseases of the pulmonary and
      cardiovascular systems. The typical Birmingham VA Medical Center patient
      presenting for surgery is male, with a national mean age of 60 years. More than
      one half of these patients have a significant history of current or prior tobacco
      abuse, and many have cardiovascular impairments. When sevoflurane became
      available, a careful review of the characteristics of the drug, as well as cost
      comparisons of inhaled agents, was done by our department of anesthesia.
      Sevoflurane appears to be an ideal inhaled anesthetic for the veteran patient
      population. If used appropriately, sevoflurane can be administered safely at a
      cost comparable to desflurane.

PMID- 9233107
TI  - Comparison of intubating conditions related to timed dosages and a nerve
      stimulator based on the measurement of acceleration using mivacurium.
AB  - A quantitative method of monitoring neuromuscular blockade has been recently
      introduced. It has been suggested, when using mivacurium, that a standardized
      passage of time be used for induction. The purpose of this study was to determine
      whether a difference existed in intubating conditions when using mivacurium
      between a timed-dose technique and the ParaGraph (Vital Signs, Inc., Totowa, New
      Jersey). In this prospective, experimental, clinical trial, 40 patients were
      randomized into two groups. Standardized induction sequences were used for both
      groups. A standardized rating tool was used to grade each intubation. Intubation
      commenced in the ParaGraph group when the monitor read one twitch. Intubation in
      the timed-dose group occurred 90 seconds after the first dose of mivacurium. The
      difference in intubating conditions score and time to intubation was tested by
      the Mann-Whitney-Wilcoxon lest. The ParaGraph group had superior intubating
      conditions when compared with the timed dose group (P = .0001). Of the ParaGraph
      group, 100% had good to excellent intubating conditions, and 85% of the timed
      dose group had fair to excellent intubating conditions. Time to intubation was
      longer in the ParaGraph group, with a mean of 216 seconds compared with 121
      seconds in the timed-dose group. The variable time to onset of mivacurium
      indicates that a timed-dose technique may yield less than optimal intubating
      conditions despite manufacturer recommendations.

PMID- 9233108
TI  - Postextubation foreign body aspiration: a case report.
AB  - Endoscopic sinus surgery performed on a healthy young male could have resulted in
      a fatal outcome when a surgically placed nasal pack became dislodged upon
      extubation and unknowingly was aspirated. Unlike the "missing" nasal packs or
      posterior pharyngeal packs placed intraoperatively, this particular pack was to
      remain in place 12 to 24 hours postoperatively, status postseptoplasty. At the
      conclusion of the case and after extubation, all visible knots, ties, and steri
      strips appeared to be intact. However, the patient displayed signs of hypoxia and
      stridor. Excessively high ventilating pressures were required to oxygenate the
      patient with the subsequent need for an emergency reintubation. A diagnosis of
      foreign body aspiration was made. Using the fiberoptic bronchoscope, it was
      discovered that one of the packs placed intraoperatively had indeed become
      dislodged and aspirated into the tracheal bronchial tree. This became a life
      threatening situation with the patient showing signs of compromised oxygenation,
      hypercarbia, tachycardia, and hypertension. The combined efforts of the surgeon,
      the anesthesia team, and the operating room personnel allowed for the prompt
      retrieval of the foreign body using the fiberoptic bronchoscope equipment.

PMID- 9233111
TI  - Organization of the Michigan Association of Nurse Anesthetists, 1937-1938.

PMID- 9233109
TI  - Anesthesia-related periodic involuntary movement in an obstetrical patient for
      cesarean section under epidural anesthesia: a case report.
AB  - Anesthesia-related periodic involuntary movements in a patient with regional
      anesthesia or etomidate anesthesia can be alarming. This case report describes
      anesthesia-related periodic involuntary movement in a patient undergoing cesarean
      section with epidural anesthesia. The anesthesia-related periodic involuntary
      movement occurred postoperatively in the recovery room. The discussion includes a
      brief review of spinal cord anatomy and physiology, as well as a review of the
      literature describing similar events.

PMID- 9233110
TI  - The safety and efficacy of granisetron in postoperative vomiting in pediatric
      patients undergoing tonsillectomy.
AB  - A high incidence of vomiting after tonsillectomy is consistently reported in the
      literature. Multiple trials with different pharmacological agents and alternative
      anesthetic techniques have been used in an attempt to decrease this, but results
      have been inconclusive and adverse effects occur frequently. The purpose of this
      study was to examine the safety and efficacy of granisetron (Kytril) in the
      prevention of postoperative vomiting in children undergoing tonsillectomy. Fifty
      four patients were included in this study. The study population was divided into
      an experimental (n = 28) and control group (n = 26) using a randomized double
      blinded technique. The experimental group was treated with granisetron 10
      micrograms/kg intravenously (IV) and the control group received saline solution
      IV. Episodes of vomiting were recorded throughout the hospital stay and for the
      24 hours after surgery. A reduction in the incidence and severity of vomiting was
      shown to be significant in the experimental group, both in the hospital and at 24
      hours postoperatively. High patient satisfaction was also reported in this group.
      Clinically, the prophylactic administration of granisetron intraoperatively in
      pediatric tonsillectomy patients should be considered to reduce the incidence and
      severity of postoperative vomiting.

PMID- 9233113
TI  - The influence of one good nurse.

PMID- 9233112
TI  - World class excellence.

PMID- 9233114
TI  - Virginia who?

PMID- 9233115
TI  - Bizarre perspective.

PMID- 9233116
TI  - Cooper's conceptual leaps unsupported.

PMID- 9233117
TI  - Intrigued, then appalled.

PMID- 9233118
TI  - Our journey.

PMID- 9233119
TI  - Yukon regains control of health care.

PMID- 9233120
TI  - CNS and NP: should the roles be merged?
AB  - Historically, nursing has adapted to changing environments and patient care
      needs. For example, the advanced nursing practice roles of clinical nurse
      specialist (CNS) and nurse practitioner (NP) involved at different times in
      response to health care delivery needs. Although the current trends in health
      care reform result from economic constraints, they nonetheless present
      opportunities for nursing to further develop the advanced practice role. Yet
      development does not have to mean creating a new role. Indeed, professional
      fragmentation-such as the separate professional streams for the CNS and NP-is one
      of the areas that hinders the nursing profession in its participation in and
      contribution to a restructured health care system. Merging these two roles into
      one would not only increase the number of nurses with advanced, standardized
      academic preparation and skills, but would provide a basis for lobbying for a
      more autonomous role for advanced nursing. As a result, nursing could respond
      proactively to changing health care needs.

PMID- 9233121
TI  - Losartan: a new antihypertensive drug.
AB  - Hypertension is a major risk factor for cardiovascular disease. It affects
      approximately one in five, or 20 per cent of Canadians. The consequences of
      untreated hypertension include myocardial infarction, stroke, congestive heart
      failure, peripheral vascular disease and renal disease. By lowering a person's
      diastolic blood pressure 5 to 6 mmHg, their chances of having a stroke are
      reduced by 35 to 40 per cent and 20 to 25 per cent for coronary heart disease.
      While the treatment for hypertension includes both nonpharmacological and
      pharmacological therapy, this article will explore losartan or Cozaar, which
      falls under the newest class of antihypertensive drugs, angiotensin II
      antagonists.

PMID- 9233122
TI  - Interviewing mothers of high-risk infants. What are their support needs.
AB  - The survival of newborns with life-threatening illness has dramatically increased
      over the past 20 years. Improved obstetrical care, earlier maternal and infant
      transfer, advanced biomedical technology and improved neonatal intensive care
      have resulted in decreased mortality and morbidity in this high-risk group. But
      the need for comprehensive care of high-risk infants extends well beyond their
      stay in neonatal intensive care units. Infants requiring intensive care at birth
      are at risk for readmission to hospital and developmental or physical impairment
      during the early years of life. In addition, the stress of infant illness and
      caring for an infant with long-term medical or developmental needs can
      permanently change the family. Thus, the improved survival rate of high-risk
      newborns has rapidly expanded the support required to meet the complex, multiple
      and long-term needs of these infants and their families during and after
      hospitalization.

PMID- 9233123
TI  - Implementing a non-restraint environment.

PMID- 9233124
TI  - Nursing by intuition.

PMID- 9233125
TI  - Five mind traps for new grads to avoid.
AB  - Self-defeating feelings are costly not only to the graduate but to the nursing
      profession. To be a successful nurse the graduate must develop skills in reacting
      to stressful situations and in coping with self-defeating feelings that may
      result if the stress is not resolved.

PMID- 9233126
TI  - Restructuring or reform?

PMID- 9233127
TI  - Cost or quality or both?

PMID- 9233128
TI  - Advancing the role of clinical nurse specialist in rural family health research.
AB  - For the clinical nurse specialist (CNS), perhaps the least implemented role is
      researcher. This is especially true of CNS research pertaining to rural family
      health. To be effective in this area the CNS must recognize the various
      definitions of rural, family, and family health. In addition, the impediments to
      CNS research in rural family health must be addressed. In this article, these
      issues are discussed, and the nurse-managed center is proposed as an ideal
      setting for conducting research into rural family health.

PMID- 9233129
TI  - You can't fool mother nature--but perhaps you can reason with her.

PMID- 9233130
TI  - Menopause: life event or medical disease?
AB  - Women throughout the world experience menopause, but it is often difficult to
      determine what it means and how it is perceived by women. A dilemma exists as to
      whether menopause should be medicalized or treated as a normal life event. The
      effects of this decision on the woman and the role of the advanced practice nurse
      in assisting the woman through this time of change are presented.

PMID- 9233131
TI  - Federal reimbursement clarified; issue of recognition shifts to the states.

PMID- 9233132
TI  - The research role of the clinical nurse specialist.

PMID- 9233133
TI  - The clinical nurse specialist as research coordinator in clinical drug trials.
AB  - With advanced clinical expertise and knowledge of the research process, the
      Master's-prepared clinical nurse specialist can engage in research in a variety
      of settings, including serving as a research coordinator for clinical trials
      required for new drug development. Based on a review of the literature, this
      challenging role will be examined in this article. The process of new drug
      development and the role of the Food and Drug Administration will also be
      examined. In addition, ethical issues related to conducting research with human
      subjects will be discussed.

PMID- 9233134
TI  - The effects of language used by caregivers on agitation in residents with
      dementia.
AB  - In this study, We addressed the problem of whether residents with a diagnosis of
      dementia would become agitated if given verbal commands at a level of language
      complexity above their comprehension ability. The study used an A-B-A research
      design. The convenience sample of 15 subjects was comprised of 11 men and 4 women
      who resided in a long-term care institution. Their mean age was 86.6 years, and
      their average length of stay in the institution was 317.3 days. The results lent
      support to the hypothesis that exposing residents with dementia to language
      beyond their comprehension ability could result in agitated behavior. The
      predominant manifestations of agitation were general restlessness, strange
      noises, and negativism. An important implication for nursing practice is that the
      language used by caregivers should match the comprehension ability of residents.
      Caregiving can thereby facilitate communication and, potentially, prevent
      agitation.

PMID- 9233135
TI  - A new perspective.

PMID- 9233136
TI  - Power, knowledge, and the discourse of specialization in nursing.
AB  - The characterization of specialization in nursing varies across different time
      periods, contexts, persons, groups, and institutions. Therefore, it may be viewed
      as a discourse. The expression of this discourse is subject to contextual
      influences and social interests. For example, its perceived congruence or
      antagonism to other major discourses, such as specialization, medicine, and
      nursing, will impact on its expression and legitimization. This article explores
      the discourse of specialization in nursing, especially as it is expressed in the
      Australian and North American context, and focuses on the power and knowledge
      issues that relate to, and constitute, the discourse.

PMID- 9233137
TI  - Sorrow and beauty: an artist's dialectic.

PMID- 9233138
TI  - Care for the patient with AIDS in the ICU: outcomes and ethics.
AB  - HIV infection and AIDS are common diagnoses in many intensive care units (ICUs)
      in the United States. Although Pneumocystis carinii currently represents only one
      quarter of all diagnoses for which HIV-infected persons are admitted to the ICU,
      it is the disease with the most clinically applicable outcome data and,
      therefore, is a model for ethical decision-making regarding patients with HIV
      infection in the ICU. Despite advances in diagnosis and treatment of HIV-related
      P. carinii, recent studies show that only 20% to 25% of the patients with acute
      respiratory failure survive to hospital discharge. Although many clinical markers
      correlate with survival, none of the individual markers or prediction scoring
      systems have the accuracy needed in clinical practice. One goal of predicting
      outcome in the ICU is to aid both the patient and the physician in making
      decisions about when to pursue aggressive therapy and when to withhold or
      withdraw such therapy. Because our ability to predict outcome is limited, advance
      directives and communication with patients and families about end-of-life medical
      care are of utmost importance. Even though it is not always possible for patients
      to predict, in advance, what they would want done in various hypothetical health
      care scenarios, quality communication between physicians, patients, and families
      with realistic discussion of outcomes and maintenance of hope and dignity can
      facilitate decisions about the use of intensive care for patients with AIDS.

PMID- 9233139
TI  - Somewhere over the rainbow.

PMID- 9233140
TI  - Music therapy: proposed physiological mechanisms and clinical implications.
AB  - ALTHOUGH STILL CONTROVERSIAL, studies suggest that music therapy can be an
      effective nursing intervention in stressful situations for decreasing anxiety,
      blood pressure, and heart rate. This article (1) reviews research related to the
      effect of music on anxiety, blood pressure, and heart rate; (2) proposes a
      potential physiological framework for the effects of music; and (3) suggests
      clinical implications for the use of music therapy in acute- and chronic-care
      settings by clinical nurse specialists (CNSs). Findings from clinical research
      suggesting that music may facilitate a reduction in the stress response include
      decreased anxiety levels, decreased blood pressure and heart rate, and changes in
      plasma stress hormone levels. Findings from laboratory research using animal
      models, provide beginning, although speculative, support for a physiological
      framework of music's influence on the stress response. Music therapy may be
      useful in a wide range of clinical settings with patients experiencing health
      problems as diverse as hypertension/cardiovascular disease, migraine headaches,
      and gastrointestinal ulcers. Suggestions for development of a music therapy
      procedure and for areas in need of additional research are offered.

PMID- 9233141
TI  - A nurse, algorithms, and the telephone: key resources for patients after hospital
      discharge.

PMID- 9233142
TI  - Cardiac surgical patients' telephone calls use of a decision-making algorithm.
AB  - CARDIAC SURGERY, ALTHOUGH becoming relatively common, still poses a significant
      life stress for patients. As a result of managed care contracting, length of stay
      has decreased to an average of 4-6 days. The Transitional Care Model was the
      framework used in identifying a way to bridge the gap between home and hospital.
      Providing patients with the unit's telephone number and encouraging them to call
      with questions was the means established toward this end. Algorithms were
      developed around the seven most frequently occurring problems so that nurses
      would be able to offer interventions consistent with our program. Approximately
      300 telephone calls have been logged in annually. Weekly review of the log
      revealed compliance with the algorithms and appropriate recommendations made by
      nurses.

PMID- 9233143
TI  - Clinical nurse specialist recognition and prescriptive authority.

PMID- 9233144
TI  - Nursing care makes a difference.

PMID- 9233145
TI  - Alternative therapies and control for health in cancer and AIDS.
AB  - People who are coping with AIDS and many forms of cancer have a sense of being
      out of control in dealing with their diseases. This stems, to a great degree,
      from the uncertainty that they feel relative to the accepted medical treatment
      for their disease. Informants in this naturalistic research study were adamant in
      their belief that alternative therapies helped them to regain a sense of control
      over their care and, thus, enhanced their health. It is important that clinical
      nurse specialists, who often serve as consultants to other nurses, understand and
      support their patients' choices of therapy. In addition, with evidence to support
      the benefit of stress reduction on length of survival, advanced practice nurses
      can play a key role in helping patients reduce stress and, hopefully, effect
      longevity and quality of life.

PMID- 9233146
TI  - A pilot study for the development of a hospital-based immunization program.
AB  - Adult immunization is often overlooked as an effective, cost-efficient means of
      preventing disease. Recently, support for the promotion of adult immunizations
      has grown in the healthcare community. One way of accomplishing timely
      immunization of adults is the concept of vaccinating patients before hospital
      discharge. This study compared two methods for implementation of a hospital-based
      immunization program. Six nursing units in a 500-bed community hospital
      participated. Three units integrated immunization into the jobs of the staff
      nurses and private physicians. On three units, immunizations were administered by
      a family nurse practitioner (FNP) who did assessments, orders, consents,
      injections, and documentation. After 3 months the two methods were compared. In
      the FNP protocol, 69 of 431 patients received vaccines. On the floors where
      physicians managed vaccines, 10 of 821 patients received vaccines. An ongoing
      immunization program continues to encourage vaccination before discharge and
      promotion of immunizations in the community.

PMID- 9233147
TI  - Leader and teacher.

PMID- 9233148
TI  - Nurses' attitudes toward patient and family education: implications for clinical
      nurse specialists.
AB  - This study had two purposes: (1) to examine nurses' attitudes toward patient and
      family education; and (2) to identify issues, barriers, and concerns related to
      patient and family education. A three-part survey was distributed to licensed
      nurses employed in a large healthcare system in Central Florida. Analysis of
      variance with posthoc multiple comparisons found differences in responses between
      different demographic groups. A model for meeting the patients' and families'
      education needs is proposed, using the various roles of the clinical nurse
      specialist to facilitate the process.

PMID- 9233149
TI  - Our continuing fight for clarity and simplicity.

PMID- 9233150
TI  - Clinical nurse specialist role confusion: the need for identity.
AB  - A common concern articulated by clinical nurse specialists (CNSs) is role
      confusion or ambiguity. Role confusion may lead to frustration, hamper
      collaboration, contribute to conflict, prevent the CNS from optimizing knowledge
      and skills, and even result in deletion of the position. Factors influencing the
      delineation of the role include the changing needs and goals of patients,
      families, interdisciplinary team members, healthcare institutions, and the
      community as well as the knowledge, skills and experience of the CNS.
      Clarification of the role requires identification of and insight into the
      specialty setting and the needs to be addressed. CNSs need to describe their role
      to other nurses considering an advanced practice role, to nursing educators
      preparing nurses to assume such roles, to administrators trying to make informed
      comparisons, and to the public seeking to meet healthcare needs.

PMID- 9233151
TI  - Call for collective voices in specialty care.

PMID- 9233152
TI  - Dermatology and the World Wide Web.
AB  - The internet is a global network of computer databases. Over the last decade the
      fastest growing area of the internet has been the World Wide Web. The World Wide
      Web now offers a vast array of dermatologic resources that can be used to support
      the delivery of patient care. The purpose of this article is to provide a brief
      explanation of the World Wide Web, and to list some of the dermatologic resources
      that are available there.

PMID- 9233153
TI  - Cutaneous hazards of the coast.
AB  - Through recreational and commercial pursuits, more people than ever before are
      coming in contact with coastal waters containing a variety of bacteria, aquatic
      flora, and sea creatures potentially harmful to the skin. It is important for
      dermatology nurses to be aware of some of the more common cutaneous hazards
      related to the coastal environment as well as the basic treatment of these
      problems.

PMID- 9233154
TI  - Laser resurfacing: the nurse's role.
AB  - CO2 laser resurfacing is an effective alternative to dermabrasion and chemical
      peels in the treatment of fine wrinkles, laugh lines, photodamaged, or acne
      scarred and pitted skin. Nurses play an important role in educating and treating
      patients, and in helping them comply with therapy.

PMID- 9233155
TI  - Patch testing for contact dermatitis.
AB  - Patch testing is perhaps not an exact science, but it is the best method
      available for identifying and confirming contact sensitivity. Illustrated step-by
      step instructions for the procedure are presented, with helpful hints to avoid
      some of the pitfalls.

PMID- 9233156
TI  - What's your assessment? Papular urticaria.

PMID- 9233157
TI  - Leadership: believing in followers.
AB  - The only hope for ongoing vitality in an organization is the willingness of a
      great many people scattered throughout the organization to take the initiative in
      identifying problems and solving them. Without this, the organization becomes
      inert, maladaptive, and descends into entropy. When leaders demonstrate, by their
      words and actions, that they truly believe that everyone in the organization is
      capable of taking on leadership activities, the organization and its people
      thrive and survive.

PMID- 9233158
TI  - Research and treatment for the major cancers.

PMID- 9233159
TI  - Attitudes to cancer may create a barrier to communication between the patient and
      caregiver.
AB  - The word 'cancer' is feared more than any other disease group, possibly because
      its course is unpredictable and anyone of any age may be affected. An effective
      tertiary health promotion programme for the newly diagnosed patient may have an
      enormous impact on the quality of life of that patient. The key to any health
      promotion programme is information and communication. Negative attitudes must be
      identified and dealt with, both patient and health promoter attitudes, before
      effective communication can take place.

PMID- 9233160
TI  - Psychosocial transitions in the long-term survivors of bone marrow
      transplantation.
AB  - Psychosocial transitions were assessed in the long-term survivors of bone marrow
      transplantation (BMT). A combination of quantitative and qualitative data from 91
      survivors led to the identification of several psychosocial phases and transit
      points after the transplant. Throughout the years post-BMT survivors were
      concerned with their sexual functioning. Adjustment with social environment was
      initiated during the first 2 years post-BMT and finalised in the fourth year post
      BMT. The third year post-BMT was characterized by a grieving phase which was
      followed by a life re-evaluation phase. Loss of control and independence were the
      main problems reported during the third and fourth year post-BMT. Occupational
      adjustment was also of main concern in the fourth and subsequent years post-BMT.
      The fifth year post-BMT featured a phase characterized by despair for those
      survivors who still had physical problems, and thoughts of what the future held
      for them. Moving on with life was a feature of those who had survived over a long
      period of time (6 years plus post-BMT), although a fraction of patients still had
      difficulties adjusting in their psychosocial environment. The identification of
      psychosocial transitions could help in understanding the specific psychosocial
      needs of the patients over time, which, in turn, could improve psychosocial
      services, with provision of professional support in crucial periods post-BMT.

PMID- 9233161
TI  - Experiences of daily life and life quality in men with prostate cancer. An
      explorative study. Part I.
AB  - Eleven men with prostate cancer were randomly chosen and interviewed during an in
      patient period at a southern Swedish hospital. The interview focused on
      functional health status in relation to daily life and life quality. In addition
      the sense of coherence scale was used, as well as the European Organization or
      Research and Treatment of Cancer (EORTC) QLQ C-30 questionnaire. The interview
      findings were analysed from a phenomenological-hermeneutic perspective and
      interpreted within the concept of transition. The entry to transition was marked
      by the men when experiencing an altered life continuum in terms of physical and
      existential fatigue, pain, micturition problems and an altered sex life. The
      passage phase was marked by descriptions of a new lifestyle where hope was a
      central internal resource, creating a positive illusion of life in order to
      endure. Their external resources were wives and family who supported physically
      (household matters, gardening) and psycho-logically (comfort, encouragement). The
      exit phase meant continuously adapting to a new life style, living with a slowly
      deteriorating functional health status, a new sense of dependency on others,
      daily life routine broken by in-patient hospital periods and contacts with
      primary health care. Thus the findings pointed more at continuously facing new
      passages than a stable exit, i.e. an ongoing transition. The areas of life
      imbalance described may serve as a basis for care assessment and intervention as
      well as supplying support of the transitional process.

PMID- 9233162
TI  - Met and unmet nursing care needs in men with prostate cancer. An explorative
      study. Part II.
AB  - Men with prostate cancer (n = 11) were interviewed during an in-patient period at
      a urological clinic, about their experiences of met and unmet needs from health
      professionals. Their perception of quality of life and sense of coherence were
      also assessed. The findings were analysed from a phenemenological-hermeneutic
      perspective and interpreted within the concept of transition. It was interpreted
      that objective functional health needs were mostly met by health professionals
      and subjective existential needs were mostly not met. The analysis revealed
      patients as passive or active receivers of care. Passive receivers were
      explicitly and implicitly stating unmet needs, or explicitly stating satisfaction
      with nursing care at the same time as implicitly contradicting, referring to
      their needs as bagatelles, unimportant, whereas active receivers talked about
      their needs explicitly with the staff and did not state implicit unmet needs.
      This suggests that nurses need to be aware of and have sensitive ears to
      undertones in statements and actively seek for patients' needs. The most
      important nursing care areas seemed to be to provide solutions to physical
      problems together with staff support including information, and acting to
      increase confidence in staff and staff availability. This encourages patient,
      wives and families, in cooperation, towards a healthy exit of transition.

PMID- 9233163
TI  - Breast cancer care: women's experience.
AB  - Medical treatments for breast cancer are undergoing rapid change. Studies of the
      management of breast cancer have investigated the psychosocial consequences of
      the diagnosis as expressed by the patients themselves, but infrequently relate
      these women's views directly to improvements in health care systems. The
      following study explores the experience of 18 women recently diagnosed as having
      breast cancer. The findings illustrate to both clinicians and managers the
      importance of considering a number of dimensions relevant to the psychosocial
      care of patients and suggest areas where health care systems may be modified to
      address the psychosocial needs of women. The results demonstrate the positive
      impact patient views can have on the development of health care services.

PMID- 9233165
TI  - A literature review of adolescence and cancer.
AB  - Cancer is a relatively rare phenomenon in adolescents and a traumatic experience
      which arouses feelings of anger, anxiety, fear and sadness. For the adolescent
      with cancer, there are missed opportunities, not only in daily life but also
      through lost social events such as dances or football games with friends.
      Adolescent cancer patients may understand the implications of the diagnosis of
      cancer but lack the personal resources or life event experience which could equip
      them to cope and make sense of the many potential problems which may accompany
      cancer. This paper reviews and explores the literature associated with the
      adolescent with cancer.

PMID- 9233164
TI  - The future of bereavement care in British general practice.
AB  - This paper discusses the future of bereavement care in British general practice
      by providing an insight into existing practice and then speculating on influences
      that may shape developments. There have been calls for the specialty to build on
      this traditional role and expand its bereavement service. Specific suggestions
      for the content of such a service are summarised. This emphasis reflects the
      increasing awareness in bereavement by other health organisations. This image of
      an expanding service needs to be contextualised within a primary care system that
      is feeling more pressurised due to increasing workload. This will continue to
      inhibit extensive service development. In addition it is important for the
      profession to consider the appropriateness of this activity. This complex debate
      has received little attention and research is required to inform and provide the
      necessary direction.

PMID- 9233166
TI  - There's no such thing as a healthy glow: cutaneous malignant melanoma--the case
      against suntanning.
AB  - One of the objectives of the 1992 United Kingdom Government White Paper 'Health
      of the Nation', is to reduce ill health and death caused by skin cancers by the
      year 2005. The Europe Against Cancer Programme shares those aims for the entire
      European population. Skin cancer was the first cancer demonstrated to have a
      chemical cause, with Percival Pott's 1775 description of squamous cell carcinoma
      of the scrotum induced by chimney soot, and skin cancers were also the first to
      be linked with ionising radiation. Currently there is a general consensus amongst
      researchers which acknowledges solar ultraviolet radiation as the major
      carcinogenic agent for the development of skin cancers. Changing attitudes and
      lifestyles affecting sun exposure is deemed responsible for the upward trends in
      incidence and mortality from skin cancers. The recognition of skin cancer as a
      preventable malignancy has implications for the health promotion role of nurses
      and of their multidisciplinary colleagues throughout Europe. This paper reviews
      the literature relating to sunlight as a risk factor for cutaneous malignant
      melanoma, and considers the behavioural issues which need to be addressed by
      healthcare professionals generally, and by nurses specifically, when establishing
      or participating in health promotion initiatives.

PMID- 9233167
TI  - A holiday break for adolescents provided by the Malcolm Sargent cancer fund for
      children.
AB  - The paper describes a holiday for a group of adolescents with cancer (from the
      Young Oncology Unit at the Christie Hospital, Manchester, UK) at Malcolm Sargent
      House, Prestwick, Scotland. The aim was to provide an opportunity for young
      people with cancer to build and to develop therapeutic relationships away from
      the pressures of hospital, home and treatment. The nature and range of care given
      by the nurses and social worker who accompanied them is described and includes
      accounts of individual progress which are demonstrated by brief case studies.

PMID- 9233168
TI  - Moderate drinking in women: a concept analysis.
AB  - This analysis clarifies the concept of moderate drinking in women. The literature
      reflects a variety of definitions of moderate drinking and refers largely to
      drinking in men. Several strategies for concept analysis suggested by Walker and
      Avant (1995) resulted in the formulation of a theoretical definition of moderate
      drinking in women applicable to practice and research. The defining attributes of
      women's moderate drinking in contemporary U.S. culture include (1) minimization
      of risks of alcohol-related problems, (2) a desire for any potential health
      benefits, (3) deliberate adoption of personal drinking guidelines based on some
      knowledge of the effects of alcohol, (4) control of when and how much alcohol is
      consumed, (5) sensitization to special drinking considerations faced by women,
      and (6) having at least one interpersonal relationship with another moderate
      drinker.

PMID- 9233169
TI  - Caring for alcoholic patients with dissociative identity disorder.
AB  - Nursing care of the alcoholic patient becomes multifaceted and complex with the
      presence of a psychiatric-mental health disorder. Although issues surrounding
      dual-diagnosis patients have been addressed in the literature, there is a paucity
      of research and theory regarding care of the patient who has both alcoholism and
      dissociative identity disorder. This article presents a synthesis of the nursing
      literature with the author's experience to elucidate factors that enhance
      healing. Nursing interventions that are unique and sensitive for the alcoholic
      patient with dissociative identity disorder are discussed.

PMID- 9233170
TI  - The experience of homeless female-headed families.
AB  - Eighty-five percent of homeless families are headed by single women who are
      extremely vulnerable and at risk for poor physical, emotional, and social health.
      The purpose of this naturalistic inquiry was to describe the experiences of 16
      women in homeless female-headed families. These women participated in tape
      recorded interviews. The themes that emerged from the interviews were a loss of
      freedom, a sense of being different, feeling down, maternal survival, and living
      under pressure. Being homeless was compared to a nightmare in which one does not
      know what will happen or where one will be from day to day. Implications for
      nursing practice and research are discussed.

PMID- 9233171
TI  - Coping style, health beliefs, and breast self-examination.
AB  - The purpose of this study was to determine the role of coping style in women's
      practice of breast self-examination (BSE). The framework was adapted from the
      Cognitive Transactional Model of Stress and Coping and the Health Belief Model.
      The convenience sample consisted of 269 women recruited from an employee list of
      a medical center and a membership list of a professional nurses' group. Survey
      booklets were distributed via interdepartmental or U.S. mail and contained
      measures of trait anxiety and defensiveness and questions related to health
      beliefs, BSE practice, and demographics. The sample was categorized by coping
      style (i.e., repressive, true high anxious, defensive high anxious, or true low
      anxious), and data were analyzed via MANOVAs, ANOVAs, and hierarchical
      regression. Results indicated that coping style predicted BSE practice (i.e.,
      proficiency, frequency) and health beliefs of barriers, confidence, seriousness,
      and susceptibility. The findings provide nurses with information for developing
      interventions to foster BSE.

PMID- 9233173
TI  - Attitudes, activities, and involvement in nursing research among psychiatric
      nurses in a public-sector facility.
AB  - The purpose of this descriptive study was to explore attitudes, activities, and
      involvement in nursing research among psychiatric nurses practicing in a public
      sector facility. A convenience sample of 90 nurses was asked to complete the
      Probe Nursing Research Questionnaire (PNRQ) and the Selby Research Attitude
      Inventory (SRAI). Nurses demonstrated positive attitudes toward nursing research
      by SRAI scores. The findings indicated that the education level was positively
      correlated (p = .003), whereas years of employment reflected an inverse
      relationship with SRAI scores (p = .013). Nurses with a high school diploma as
      their highest level of education scored lowest; those with an advanced education
      level scored highest. Nurses employed longer at the public-sector facility scored
      lower on the SRAI than those recently hired. The cross-product of age/employment
      with SRAI scores found that nurses who were older and employed for a greater
      number of years had lower research attitude scores (p = .003). Strategies are
      offered to enhance nursing research activities and involvement in public-sector
      facilities.

PMID- 9233172
TI  - Family adaptation: adult sons with long-term physical or mental illnesses.
AB  - A descriptive study of 62 family members with an outpatient adult son with a long
      term physical (8 families) or mental (3 families) illness using multiple methods
      and multiple family members' perspectives. Family members completed FILE, FIRM,
      FAM-III. FACESIII, the Progress Evaluation Scale, and the Nottingham Health
      Profile. Single-item indicators were based on Rolland's (1988) psychosocial
      typology of illness, Mishel's (1988) components of uncertainty of illness, and
      selected demographics. On most of the instruments and their subscales, there were
      few statistical differences. Family members often did not report the same
      diagnosis. Based on the qualitative data, families coped by "just working with
      it" or "trying to step back."

PMID- 9233174
TI  - Using the quality improvement process to affect breastfeeding protocols in United
      States hospitals.
AB  - Engaging in the Quality Improvement Process represents an opportunity for
      lactation consultants and breastfeeding advocates to examine and reevaluate
      hospital breastfeeding policies and procedures. Cause and effect diagrams that
      explore the problem of an 8-hour-old baby who has not yet breastfed are presented
      as examples of a quality tool.

PMID- 9233175
TI  - Nipple pain: an alternative explanation.

PMID- 9233176
TI  - Nipple shields used successfully.

PMID- 9233177
TI  - Caution regarding nipple shields.

PMID- 9233178
TI  - MALC on-line.

PMID- 9233179
TI  - Will longer hospital stays really help?

PMID- 9233180
TI  - The rewards outweigh the efforts: breastfeeding outcomes for mothers of preterm
      infants.
AB  - This study describes the rewards and efforts of breastfeeding for mothers of
      preterm infants. Using a semi-structured interview guide, 20 mothers of preterm
      infants were interviewed in their homes approximately 1 month after infant
      discharge from a Level III NICU. Mothers described the following rewards of
      breastfeeding: knowing they were providing the healthiest nutrition for the
      infant, enhancing closeness between the mother and infant, perceiving infant
      contentment and tranquility during breastfeeding, providing convenience for the
      mother, and giving the mother a tangible claim on the infant. Most mothers
      identified some "efforts" associated with breastfeeding their preterm infants,
      but indicated that overall, breastfeeding was a rewarding experience. These data
      provide scientific support for the promotion and facilitation of breastfeeding
      for mothers of preterm infants, in that mothers perceive specific emotional
      advantages that they relate to the breastfeeding experience.

PMID- 9233181
TI  - Documentation of second-by-second breastfeeding behaviors using a novel method.
AB  - The specific way nursing patterns influence the duration of postpartum amenorrhea
      is unknown. This may result from the shortcomings of available methods: the daily
      log and recall. We tested these against a novel method, an event monitor (EM),
      consisting of a wrist-worn stopwatch that stores events. Exclusively
      breastfeeding women (n = 11) were assigned randomly to use each of the three
      methods twice during a 2-week period surrounding Weeks 4, 8, and 12 postpartum.
      More nursing episodes were recorded with the EM than log during Week 4 (p < 0.03)
      and Week 8 (p < 0.02). EM captured more episodes than recall during all study
      periods (p < 0.004). The EM was considered as acceptable and accurate to mothers
      as the other methods and, therefore, is a useful option for documenting
      breastfeeding patterns.

PMID- 9233182
TI  - Support of breastfeeding through telephone counseling in Korea.
AB  - This study analyzed the problems of breastfeeding mothers who used a telephone
      consultant for advice. In one South Korean metropolitan area, 92 breastfeeding
      mothers received telephone consultation between August 24, 1994 and June 30,
      1995. Mothers learned about the availability of the consultant from UNICEF,
      hospitals, and the general media. Problems were grouped into 11 categories (and
      22 nursing diagnoses) the most common of which was breast milk insufficiency (22
      cases). Fourteen mothers sought consultation about their infants' diarrhea or
      frequent stools. The findings in this study have practical implications for
      breastfeeding promotion and education in Korea.

PMID- 9233183
TI  - Assessment of students' attitudes toward breastfeeding.
AB  - A self-administered survey questionnaire was distributed to 346 high school and
      244 college students in Alabama to explore their perceptions of breastfeeding.
      Only 135 acknowledged having been breastfed. Embarrassment was perceived as a
      major barrier to breastfeeding; less than half thought breastfeeding should be
      done publicly. However, respondents had generally positive attitudes about
      breastfeeding. They intended to support breastfeeding of their own child; thought
      that breastfeeding was more healthful than bottle-feeding and more convenient;
      and that breastfeeding is not obscene nor does it make a woman less attractive.
      Over half received breastfeeding information from home, school, and television.
      Further, both high school and college students supported breastfeeding education
      in schools. These findings suggest that although fears of embarrassment is a
      major barrier to breastfeeding, the students showed overall positive attitudes
      about breastfeeding despite the region's low breastfeeding rate. Breastfeeding
      promotional programs should address the stigma of embarrassment associated with
      breastfeeding.

PMID- 9233184
TI  - A comparison of two U.S. surveys of infant feeding.
AB  - This study compares the 1988 National Maternal and Infant Health Survey (NMIHS)
      and the 1989 Ross Laboratories Mothers Survey with respect to sample
      characteristics and proportions of women who breastfed. Weighted proportions of
      women included in the two surveys were compared according to various
      characteristics to see how well they represented U.S. childbearing women. A z
      statistic was produced to test for significant differences in the proportions who
      breastfed. In 1988-89, 52.2% of American women breastfed according to the Ross
      survey and 53.4% according to the NMIHS. Despite differences in sample size,
      sampling technique and the application of sample weights, the difference between
      the surveys was only 1 percentage point, and most levels of most variables
      examined were comparable. The Ross survey is a valuable source of data because it
      is ongoing, and it is generally corroborated by the NMIHS. The NMIHS is probably
      more representative of the U.S. population of childbearing women, and is a
      reliable source of data for setting U.S. objectives concerning infant feeding,
      and for the study of other issues vis-a-vis breastfeeding.

PMID- 9233185
TI  - Fathers and breastfeeding: a review of the literature.
AB  - Research on breastfeeding support has consistently identified fathers as an
      important source of support in the decision to breastfeed and in its
      implementation. The literature indicates that fathers influence four aspects in
      particular: the breastfeeding decision, assistance at first feeding, duration of
      breastfeeding, and risk factors for bottle feeding. Research which focuses on
      fathers has added to our understanding of their attitudes, knowledge, and coping
      techniques regarding breastfeeding. This paper reviews the research findings in
      each of these areas, and offers suggestions for further research.

PMID- 9233186
TI  - Lactational headache: a lactation consultant's diary.
AB  - There are few references to lactational cephalalgia (headache) in the literature,
      and these few such headaches are attributed to oxytocin surges associated with
      the milk-ejection reflex. The case described here differs, in that the apparent
      trigger was overfulness, rather than an oxytocin surge, that occurred when the
      infant began sleeping through the night or after a missed, delayed, or partial
      feed. Headaches were relieved by putting the baby to the breast and the resultant
      milk-ejection reflex. This case study describes maternal coping strategies from 5
      months postpartum until weaning was completed at 12 months.

PMID- 9233187
TI  - Cup feeding: problems created by incorrect use.
AB  - This case describes an infant who was fully fed breast milk by cup, because of
      poor attachment and breast refusal. Faulty method of cup feeding caused the
      infant to aspirate breast milk and hindered, rather than assisted, the retention
      of oral skills required for attachment at the breast. Withdrawal of the cup and
      use of other feeding techniques produced good mouth closure and deep swallowing.

PMID- 9233188
TI  - Maternal psychological issues in the experience of breastfeeding.
AB  - This paper describes various situations wherein psychological etiologies of
      breastfeeding failure were discovered after exhausting the usual means of
      assisting the new mother. This discussion involves a look at possibilities of why
      and when to consider emotional difficulties and when to provide referrals for
      assistance.

PMID- 9233189
TI  - Use of nonnarcotic analgesics during breastfeeding.

PMID- 9233190
TI  - Human milk banking in Germany.

PMID- 9233191
TI  - Statistical report of the 1996 IBLCE Examination.

PMID- 9233192
TI  - Staying abreast of the latest scientific controversies: infant feeding and
      insulin-dependent diabetes mellitus.

PMID- 9233194
TI  - Antidepressant use during breast feeding.

PMID- 9233193
TI  - The cost of not breastfeeding: a commentary.
AB  - Breastfeeding, a valuable natural resource, promotes health, helps prevent infant
      and childhood disease, and saves health care costs. Additional annual national
      health care costs, incurred for treatment of four medical conditions in infant
      who were not breastfed were estimated. Infant diarrhea in nonbreastfed infants
      costs $291.3 million; respiratory syncytial virus, $225 million; insulin
      dependent diabetes mellitus, from $9.6 to $124.8 million; and otitis media, $660
      million. Thus, these four medical diagnoses alone create just over $1 billion of
      extra health care costs each year. Breastfeeding may also enhance intellectual
      development of children according to at least one medical research study. The
      potential societal benefits of more intelligent children is incalculable even
      though it cannot be directly measured in terms of dollars. Finally, it was
      calculated that an additional $2,665,715 in federal funds is needed yearly in
      order for WIC to provide infant formula to nonbreastfeeding mothers. For the
      average family, the cost of purchasing formula is twice the cost of supplemental
      food for the breastfeeding mother. Breastfeeding education and support should be
      an integral part of health care, especially under managed care which rewards the
      prevention of health problems and reduced use of health services.

PMID- 9233195
TI  - Canadian Pharmaceutical Association Position Paper on Breastfeeding and Infant
      Nutrition.

PMID- 9233196
TI  - Breastfeeding and severe maternal pain.

PMID- 9233197
TI  - Silicone expertise.

PMID- 9233198
TI  - Further caution re: nipple shields.

PMID- 9233199
TI  - A descriptive study of breastfeeding practices and policies in Missouri
      hospitals.
AB  - All Missouri hospitals that offer maternity services were assessed to measure
      their compliance with WHO/UNICEF Baby Friendly Hospital Initiative (BFHI).
      Representatives from seventy six hospitals responded to a telephone survey
      relating to hospital breastfeeding practices and policies as defined by BFHI's
      Ten Steps to Successful Breastfeeding. No hospital fully supported the Ten Steps.
      Compliance with the WHO/UNICEF criteria varied greatly. The least support was for
      Step I, only 28% of hospitals had a written breastfeeding policy that was
      communicated to all staff. The greatest support was for Step 3, 93% of hospitals
      had staff who informed all pregnant women of breastfeeding benefits. In order to
      increase breastfeeding rates and duration, administrators of hospitals that offer
      maternity services must increase their efforts to consistently implement the Ten
      Steps, to become more baby friendly, and to more fully establish a breastfeeding
      culture within their institutions.

PMID- 9233200
TI  - Breastfeeding counseling by health care providers.
AB  - This study sought to identify the content and source of information given to
      prospective breastfeeding mothers. The population included 111 mothers attempting
      to breastfeed at a community hospital during a 3-month period. Questionnaires
      were used to assess prenatal preparation and specific breastfeeding issues
      discussed by health care providers. During the prenatal period, 23% of mothers
      received counsel from their obstetrician, 47% from books, and 21% from classes.
      Postpartum, nurses provided breastfeeding information to 87% of mothers whereas
      obstetricians and pediatricians provided advice to 27% and 33% of mothers,
      respectively. Many women do not receive supportive breastfeeding counseling from
      physicians. Health care providers must develop better methods of prenatal and
      postpartum education to enhance breastfeeding initiation and continuation.

PMID- 9233202
TI  - Prenatal breastfeeding education: its effect on breastfeeding among WIC
      participants.
AB  - The effect of prenatal breastfeeding education on breastfeeding incidence and
      duration was determined among 31 prenatal WIC participants. The subjects,
      assigned to a control group (n = 17) or experimental group (n = 14), received
      prenatal nutrition education through the WIC program. The experimental group
      received at least one breastfeeding education class. There was no significant
      difference in breastfeeding incidence between the groups, however, there was a
      significant difference in breastfeeding incidence by parity (p < 0.05). There was
      a significantly higher percentage of women still breastfeeding at 3 and 4 months
      postpartum in the experimental versus the control group (p < 0.05). The control
      group breastfed for 29.5 +/- 43.6 days, while the experimental group breastfed
      for 76 days +/- 104.3 (p = .05). Multiparous women who had bottle-fed previous
      children breastfed for a shorter duration (18 +/- 22 days) than primiparous women
      (60 +/- 87 days) (p < .07).

PMID- 9233201
TI  - Breast milk composition after exercise of different intensities.
AB  - The purpose of this study was to determine if breast milk composition changed
      significantly following exercise conducted at different intensities. Nine
      postpartum women exercised on a treadmill up to maximal oxygen uptake (100% of
      VO2max) on the first laboratory visit, for 30 minutes on two subsequent occasions
      (50% and 75% of VO2max) and also performed a nonexercise control session. Blood
      and breast milk were collected prior to exercise, immediately after exercise, and
      at 30, 60, and 90 minutes postexercise. Blood samples were analyzed for lactic
      acid (LA) while milk samples were analyzed for LA, pH, lipid, ammonium, and urea.
      Milk LA after the 100% intensity session was significantly elevated through 90
      minutes postexercise, while there was no significant increase in milk LA at any
      collection time after the 50% or 75% intensity sessions. There were no
      significant differences in milk pH, lipid, ammonium, or urea measurements after
      any of the exercise sessions. These data show that unlike maximum intensity
      exercise, moderate intensity exercise does not increase breast milk LA content.

PMID- 9233203
TI  - Contamination in expressed breast milk following breast cleansing.
AB  - The purpose of this study was to determine if preexpression breast cleansing
      reduced the bacterial count in expressed breast milk. The study involved the
      collection of 178 breast milk samples (89 matched samples); 38 matched samples
      were from mothers of term infants and 51 matched samples were from mothers of
      preterm infants. One half of the samples were collected following breast
      cleansing with Phisoderm and tap water. The other half were collected following
      breast cleansing with tap water only. Hand and equipment washing with Phisoderm
      and tap water preceded all sample collections. Storage containers were sterile.
      Samples were cultured for pathogenic and nonpathogenic bacteria and examined at
      24 and 48 hours. Data were analyzed by Wilcoxon Matched-Pairs sign test and Chi
      square. Breast cleansing with Phisoderm and water was not more effective than
      water alone at reducing nonpathogenic bacteria or eliminating pathogenic
      bacteria. Mothers of preterm infants had higher levels of both nonpathogenic and
      pathogenic bacteria than mothers of full-term infants. The most common form of
      bacterial contamination was coagulase-negative Staphylococcus epidermidis. This
      particular bacteria is found in higher levels in the stools of breast fed infants
      than formula fed infants and it also the most common contaminant found in the
      blood of preterm infants who develop sepsis. The findings of this study reveal
      that chemical interventions may not be effective at rendering breast milk free
      from pathogenic bacteria. More research is needed to determine the optimal
      cleansing protocol to achieve bacterial decontamination of breast milk or to
      determine the clinically acceptable level of contamination based on the effects
      on infants.

PMID- 9233204
TI  - Do labor medications affect breastfeeding?
AB  - Do labor medications affect breastfeeding? Few studies examine breastfeeding as
      an outcome of labor medication. While parents may be told that labor medications
      and epidurals have no effect on newborns, the literature reports significant
      neurobehavioral effects of these medications on the newborn and the mother-infant
      relationship.

PMID- 9233205
TI  - Bubble palate and failure to thrive: a case report.
AB  - In this report, a mother presents at 29 days postpartum with extremely sore
      nipples. Her infant is 1 1b 2 oz (511 gms) below birth weight, a continuing
      weight loss consistent with failure to thrive. Failure to thrive may be caused by
      a variation in infant palatal structure (VIPS) such as a bubble palate. The
      mother demonstrated correct latch-on, positioning, and soreness secondary to
      nipple candidiasis concealing the VIPS as a hidden component to this
      breastfeeding problem. A thorough assessment of the infant at breast, the
      infant's oral anatomy and the mother's breasts revealed the VIPS and information
      necessary for treatment. Alternative positioning and repatterning of oral
      behavior resolved the breastfeeding problem. A variation in infant palatal
      structure may be a hidden breastfeeding problem and needs to be considered.

PMID- 9233206
TI  - Breastfeeding after strenuous aerobic exercise: a case report.
AB  - There are no documented adverse effects of breastfeeding after long distance
      running. This case describes an exclusively breastfed baby who cried after being
      breastfed about 1-2 hours following his mother's 5-mile run. When artificial baby
      milk was substituted for the postrun feeding only, the inconsolable crying did
      not occur. Testing the mother's breast milk before and after running showed a
      similar level of lactic acid; no other component was tested. Further research is
      needed in this area.

PMID- 9233207
TI  - Observations based upon multiple telephone contacts with new breastfeeding
      mothers.
AB  - Common themes and phenomena were identified by a lactation consultant providing
      an average number of nine follow-up phone contacts per mother during an average
      of 12 1/2 weeks postpartum. Over 600 mother-infant couples received lactation
      support services in the past 6 years. Eighty-six percent of the mothers receiving
      this telephone support breastfed for at least 1 month, 46% breastfed at least 3
      months, and 23% breastfed for at least 5 months. Co-sleeping was encouraged in
      the first week postpartum, as was nursing one breast per feed. Normal
      breastfeeding was identified when the mothers nursed comfortably (save for first
      minute latch-on pain), when they reported having fun with their babies, when
      their babies woke spontaneously to feed and to look around, when their babies
      urinated sufficiently and either had bowel movements or passed flatus, and when
      their babies were observed to smile. Anticipatory guidance about areolar
      engorgement, growth sports, and continuing to nurse despite maternal illness
      reduced bottle use in the first few weeks. The majority of women had no problems
      establishing breastfeeding with daily telephone contact for the first 5-7 days
      postpartum, one to three calls per week for the next few weeks, and gradually
      diminishing calls thereafter. Telephone calls were initiated by the LC, as only
      12-16% of mothers called for help, even though they all received the LC's home
      telephone number.

PMID- 9233208
TI  - Breastfeeding the sleepy baby.
AB  - Sleepy babies can be a source of frustration to both mothers and health care
      providers during the early days of breastfeeding. This paper looks at some
      reasons for excessive sleepiness and offers suggestions for helping sleepy babies
      to breastfeed using the baby as a guide.

PMID- 9233210
TI  - How North American donor milk banks operate: results of a survey, Part 1.

PMID- 9233209
TI  - Principles of drug transfer into breast milk and drug disposition in the nursing
      infant.
AB  - There are numerous factors to consider when assessing the safety of drugs in
      lactating women. Drug properties facilitating transfer into milk as well as the
      pharmacokinetic properties of the drug in the mother and infant must be
      evaluated. Drug properties which promote low milk concentrations are: large
      volume of distribution, high protein binding, low lipid solubility, ionization at
      physiologic pH and large molecular weight. Following transfer into breast milk,
      drugs with low bioavailability and short elimination half-lives in neonates have
      improved safety.

PMID- 9233211
TI  - Eyes on the volunteers: going that extra mile!

PMID- 9233212
TI  - Aqueous tube shunts for refractory glaucomas.

PMID- 9233213
TI  - Ophthalmic nursing: the way we were.

PMID- 9233214
TI  - Refitting the previous contact lens wearer.
AB  - The wide variety of options available for refitting today's contact lens wearers
      enables us to select modalities that provide the best chance of long-term success
      based on patient lifestyle and history of previous problems. The key to solving
      these problems lies in good communication, knowledge of the range of lenses
      available in each situation, including their advantages and disadvantages, and
      the establishment of mutual trust between fitter and patient.

PMID- 9233215
TI  - Complications from an intraocular lens: a case presentation.

PMID- 9233216
TI  - Managing an office practice effectively.

PMID- 9233217
TI  - Self-assessment quiz. Strawberry hemangioma.

PMID- 9233218
TI  - Poor science makes poor practice.

PMID- 9233220
TI  - With regard to animal experimentation.

PMID- 9233219
TI  - Study investigating what midwives are advocating regarding 'co-sleeping'.

PMID- 9233221
TI  - To touch or not to touch.

PMID- 9233222
TI  - Achieving Baby Friendly status in a large city hospital.

PMID- 9233223
TI  - The legal aspects of sterilisation. Part 2.

PMID- 9233224
TI  - Midwife-run clinic.

PMID- 9233225
TI  - Support during screening--an NCT report.

PMID- 9233227
TI  - AIMS. Association for Improvements it the Maternity Services.

PMID- 9233226
TI  - Crediting clinical practice.

PMID- 9233228
TI  - Efficiency and health.
AB  - Efficiency has become of central importance in health care and is seen as wholly
      laudable. It appears to offer a precise and objective means of evaluating and
      comparing institutions, practices and individuals, and is a principle that
      underlies techniques of cost-benefit analysis and other methods of option
      appraisal. However, there is a need to examine the concept of efficiency and
      explore the problems of its application within health care. Efficiency is a value
      laden notion and it cannot be used as a means of making value judgements from
      purely factual premises. We have to choose the inputs and outputs in our
      calculations, and what limits to set on their scope. Efficiency calculations may
      require us to measure what cannot be quantified, and to treat as commensurable
      what is incommensurable. There are circumstances in which considerations of
      efficiency are inappropriate or even immoral.

PMID- 9233229
TI  - Competing ideologies in health care: a personal perspective.
AB  - With the introduction of general management and then of planned markets into the
      National Health Service (NHS), health care in the UK has gone through a massive
      amount of change. The effect on those working for the NHS has been 'challenging'
      and often confusing. This paper aims to clarify what is happening by taking an
      ideological perspective: what ideologies exist, how they are changing and the
      strategies being used to ensure their survival. Ideologies are basically about
      power. The relationship between market, managerial and professional ideologies is
      analysed using charters, codes of conduct and other associated documents. A
      tentative conclusion is reached that professional ideologies are able to adjust
      to the overriding market/consumerist ideology. However, the managerial ideology
      is having difficulty in gaining any real ground against the professional ideology
      and is having to move strategically by using audit, not just of finance, but also
      of clinical judgement, to gain power.

PMID- 9233231
TI  - Reflective practice: decoding ethical knowledge.
AB  - This article analyses reflective practice by exploring ethical knowledge-in-use
      and the influence of context on professional nursing practice. Is ethical
      knowledge used in an appropriate context? The author identifies and discusses the
      theoretical underpinnings of reflective practice and offers an alternative
      paradigm to the generation and use of ethical knowledge in practice. The message
      to teachers and practitioners is decoded to facilitate teaching and learning.
      This article is an extension of the work done by the author and described by him
      in Nursing Ethics.

PMID- 9233230
TI  - Developing moral imagination and the influence of belief.
AB  - Moral imagination has been described by Murdoch as 'a way of seeing'. The focus
      of concern here is the influence of belief upon moral imagination and those
      attitudes that are needed if moral imagination is to be developed. The
      perspective adopted endorses a Humean recognition of the potent influence of
      personal experience upon those beliefs that are held, and therefore upon how we
      see the world. Kantian commitment to the power of the will, and to the ability of
      individuals to choose who they wish to be, allows room for optimism, a view which
      is supported by the findings of Liaschenko.

PMID- 9233232
TI  - Nursing ethics into the next millennium: a context-sensitive approach for nursing
      ethics.
AB  - The aim of this article is to argue for the need for a context-sensitive approach
      to the understanding of ethical issues in nursing practice as we face the next
      millennium. This approach means that the idea of universalism must be questioned
      because ethics is an interpersonal activity, set in a specific context. This view
      is based on issues that arise in international collaborative research as well as
      in research focused on ethical problems in nursing practice. Moral values are
      indigenous to a particular culture and influence beliefs about health and illness
      as well as what priorities are to be made in providing health care. Nursing
      practice must include thoughtful reflection on the meaning of moral concepts and
      principles in terms of culture. Theoretical developments in nursing ethics must
      be based on empirical research focusing on contextual aspects of health care.

PMID- 9233233
TI  - Not for resuscitation: two decades of challenge for nursing ethics and practice.
AB  - Since the 1970s, the designation of some patients as 'not for resuscitation'
      (NFR) has become standard practice in many health care facilities. Considerable
      disquiet has subsequently arisen about the way these decisions are implemented in
      practice. Nurses, in particular, often find themselves initiating or withholding
      cardiopulmonary resuscitation (CPR) in situations characterized by verbal orders,
      euphemistic documentation and poor communication, and when consultations with
      patients about their CPR choices often do not take place. These practices have
      developed in large part because a clear legal foundation for withdrawal of
      treatment decisions such as NFR is still lacking in many countries. The problems
      with NFR were identified in the 1970s and 1980s and are not new, but, as yet, we
      have not been able to bring about the necessary changes, in effect to translate
      broadly accepted ethical principles into clinical practice. This paper explores
      some of the reasons for this and provides a review and analysis of the main
      issues, including NFR guidelines and the nursing role in NFR decision-making.

PMID- 9233234
TI  - Selected ethical issues in planned social change and primary health care.
AB  - This paper discusses two interrelated concepts: (1) the ethics of planned social
      change and (2) primary health care. It takes the World Health Organization's
      definition of primary health care as a point of departure to examine four
      identified potential areas where ethical dilemmas may occur. In addition,
      questions are raised about nursing education, as well as about the class and
      status differences between nurses and patients and communities. It takes the
      position that our first task is to encourage more discussion and examination of
      ethical issues in the planned social change of primary health care.

PMID- 9233235
TI  - The nurse shortage problem in Japan.
AB  - This article discusses the serious problem of the shortage of about 50,000 nurses
      in Japan today. If efficient measures to solve it are not adopted by
      administrators, it is clear that the shortage will become still more alarming in
      the future, in a society with more people in advanced years and in which the
      numbers in the younger generation will decrease from now on. The main factors
      behind the Japanese nursing labour shortage are, among others: a rapid increase
      in the number of hospital beds between 1986 and 1989, poor working conditions;
      and nurses' low social position in their places of work. Behind these factors,
      there has always been a contempt for the art of nursing in our society. Why has
      Japanese society made light of nursing? Three points can be identified:
      traditional discrimination against women; our disregard for a religious
      mentality; and our short history of hospital nursing. To overcome these problems,
      we must first of all change fundamentally our sense of values, such as love for
      one another and compassion. We must now reconstruct a caring culture in our
      society.

PMID- 9233236
TI  - Morbid obesity: a chronic disease with an impact on wounds and related problems.
AB  - Morbid obesity is a chronic disease that manifests as a steady, slow, progressive
      increase in body weight. Because of both emotional and physical reasons, obese
      people resist pursuing healthcare and may be more difficult to care for. In
      taking a practical approach to skin and wound care, using an interdisciplinary
      team is valuable. Difficulty in assessment stems from problems such as equipment
      that is too small or as patient uncooperativeness. Skin/wound problems which are
      common, yet more difficult to manage for these patients, include pressure ulcers,
      tracheostomy care (potentially resulting from ventilatory insufficiency),
      candidiasis, tape-related skin tears, incontinence and lymphedema. In order to
      offer care and support to these patients and their families, clinicians must
      acknowledge and manage any personal prejudice they may have toward this patient
      population. A comprehensive patient-focused plan of care is the goal. With this
      article are included four annotated suggested readings introducing topics such as
      the failure of behavioral and dietary treatments for obesity, theoretical and
      practical aspects of obesity assessment, current views on obesity (such as a move
      back to pharmacotherapeutic treatment), and the psychological aspects of severe
      obesity.

PMID- 9233237
TI  - Necrotizing fasciitis: case study of a nursing dilemma.
AB  - Necrotizing fasciitis usually manifests as a low grade cellulitis that quickly
      deteriorates to a limb and life threatening soft tissue infection. Immediate
      surgical debridement is essential, after which wound management becomes the
      nurse's primary concern. Case #1 reports on a 72 year old female who, upon
      presenting to the ER with a "sore bottom," subsequently had these diagnoses: (1)
      anal-rectal abscess, (2) Fournier's gangrene, (3) ulcerative enterocolitis, (4)
      chronic blood loss/anemia, and (5) protein caloric malnutrition. After
      debridement, her anal-rectal wound extended from labia to left buttocks. Care was
      multidisciplinary and included applying a water based aloe gel and saline soaked
      gauze twice a day. After 45 days, the wound exhibited a pink base with
      granulation tissue and contraction of the wound edges. Case #2 reports on a 48
      year old male with seroma of the left leg secondary to a crush injury. Within
      three days he developed deep vein thrombosis in that leg as well as two large
      seroma cavities on either side of the thigh. Care included packing with the aloe
      gel and saline soaked sponges. Two weeks after admission, the anterior wound was
      covered with a split thickness skin graft while partial closure of the lateral
      cavity was attempted unsuccessfully with retention sutures. After five weeks,
      healing was complete for the anterior wound and 95 percent complete for the
      posterior wound.

PMID- 9233238
TI  - The usefulness of topical application of essential fatty acids (EFA) to prevent
      pressure ulcers.
AB  - This study investigated whether the topical application of essential fatty acids
      improves hydration and elasticity and helps prevent skin breakdown in individuals
      with poor nutritional status. Between June 1995 and July 1996, 86 patients,
      equally divided into two groups, underwent double-blind research (mean age = 60;
      range 26-78). All patients had a Norton Scale score of 9 and were fed orally a
      high-protein diet and/or received parenteral nutrition (92% were severely
      malnourished). Pressure ulcer prevention was the same for both groups. Every 8
      hours, approximately 20 ml of solution A (1.6 gr EFA with linoleic acid extracted
      from sunflower oil, 112 UI vitamin A, and 5 UI Vitamin E) or B (1.6 gr mineral
      oil, 112 UI Vitamin A, and 5 UI Vitamin E) was applied all over the body
      inclusive of all potential wound sites for a mean of 21 days. In group A, two
      patients developed ulcers (both Stage I, one per patient); 42 (98%) had hydrated
      skin and 32 (76%) maintained skin elasticity. In group B, 12 (27%) developed
      ulcers (all Stage II, ten with 1 ulcer, two with 2 ulcers); 9 (22%) had hydrated
      skin while 34 (78%) showed scaly skin/deep dehydration; 10 (24%) maintained skin
      elasticity while 33 (76%) showed a loss of elasticity. These results lead us to
      believe that essential fatty acids really do make a difference in the skin.

PMID- 9233239
TI  - HCFA's decision to not cover electrical stimulation for the treatment of wounds
      is delayed 60 days.

PMID- 9233240
TI  - [A Gordian knot].

PMID- 9233241
TI  - [Latex--curse or blessing for medicine. 3. Allergy-causing substances can be
      minimized].

PMID- 9233242
TI  - [Old age is no analgesic].

PMID- 9233243
TI  - [Carpe diem--we all live on borrowed time].

PMID- 9233245
TI  - [Ever fewer nurses are caring for ever more patients].

PMID- 9233244
TI  - [Cooperation is not just helping work satisfaction].

PMID- 9233246
TI  - [Successful rehabilitation is being punished by health insurance].

PMID- 9233247
TI  - [Quality management in old age homes according to the ISO standards. 2.
      Satisfaction of residents starts with the working team].

PMID- 9233248
TI  - [Nursing courses in Germany. 10. Anthropology and ethics are of importance in
      Nuremberg].

PMID- 9233249
TI  - [Strategic personnel development in health care. 2. The introduction requires
      basic decisions in service facilities].

PMID- 9233250
TI  - [Managers need much energy to overcome their coworkers' inner resistances].

PMID- 9233251
TI  - [Modern methods of wound treatment. 1. One wound is not the same as all the
      others].

PMID- 9233252
TI  - [Quality assurance in an intensive care unit: standards are being developed for
      the care of patients with liver and kidney transplantations].

PMID- 9233253
TI  - [The reuse of disposable equipment. Condition: the patient's health must never be
      endangered].

PMID- 9233254
TI  - [Intensive care meeting in Munich. We are caring also for mind and soul].

PMID- 9233255
TI  - [Improvement of quality in the hospital--is it necessary or is it a fashion
      trend? Critical considerations on fascination and on risk].

PMID- 9233256
TI  - [University Reform Legislation. A backwards step].

PMID- 9233257
TI  - [Vitamin deficiencies. Repercussions on women's health].

PMID- 9233258
TI  - [External cranio-cervical ligaments].

PMID- 9233259
TI  - [What are the needs of neurology patients?].
AB  - Problems and complications exhibited by neurology patients are identified so that
      the proper nursing care actions can be determined and appropriate treatment can
      be initiated. A look at the various problems that might appear include:
      respiratory, nutrition and hydration, urinary and intestinal elimination,
      musculoskeletal and circulatory, emotional, communication and security. Lastly,
      some little known considerations are discussed regarding the nursing implications
      of caring for these individuals.

PMID- 9233260
TI  - [Nurses in the middle of a war. Working to change the outlook].

PMID- 9233261
TI  - [Cancer patients. Self-care].

PMID- 9233262
TI  - [Care of skin ulcers in hospital and outside].

PMID- 9233263
TI  - [Nursing diagnosis: a strategic plan].
AB  - Presented is the strategy followed by a primary care area as regards the
      introduction of a nursing methodology and the use of nursing diagnostics in
      practical hands-on care. By defining their nursing activities they hope to
      broaden the services of primary care nurses. The methodology subscribed to here
      is the result of nine months of work. The authors emphasize the importance of
      using an instrument of systematized care as well as the need for good
      communication, motivation and training among the professional team in the
      process.

PMID- 9233264
TI  - [Fracture of the proximal third of the femur. II].
AB  - The second of a two part series dealing with fractures of the femur.
      Postoperative health care is the focus of this article, with special attention
      paid to possible complications and what effect they might have on the patient's
      quality of life. Specific nursing care plans and procedures help prepare the
      patient to confront their disability in the best physical and psychological state
      possible.

PMID- 9233265
TI  - [Decubitus ulcers: evaluation of a protocol].
AB  - An evaluation of the incidence, treatment and prevention of decubitus ulcers is
      presented within the framework of an Internal Medicine unit. Chosen for the study
      from a pool of admitted hospital patients were 60 people believed to be at risk
      of ulceration. They were evaluated according to established criteria and they
      were then followed during the length of their stay. Of these 60 patients, 38
      later developed lesions. Of these 38, 63.2% were admitted with ulcers and 36.8%
      developed their pressure sores while in the hospital. 65.3% of those ulcers
      healed completely during the patients stay; 7.6% actually got worse. A
      significant statistical risk between the appearance of ulcers and the evaluated
      at risk factors was not found.

PMID- 9233267
TI  - [Treatment in patients with borderline disorder: objectivity and subjectivity].

PMID- 9233266
TI  - [Arthroscopy of the ankle].
AB  - Technical advances have facilitated the use of arthroscopic surgery, converting
      it into a useful technique for the treatment and diagnosis of diverse ankle
      pathologies. Ankle arthroscopia represents a greater challenge than other
      arthroscopic operations due to the anatomical limitations involved. This article
      reviews the equipment and techniques used for this procedure.

PMID- 9233271
TI  - [Masteron's approach to the borderline disorder of the self].
AB  - Borderline pathology challenges the mental health field with its dynamic
      complexity and management difficulties. James F. Masterson, M.D., is a leading
      authority and pioneer in the diagnosis and treatment of the Borderline Disorder
      of the Self. His work is based on 30 years of intensive clinical experience and
      research, integrated with a synthesis of the major psychodynamic concepts,
      including developmental theory, object relations, and concepts of the Self.
      Masterson's specific theory and applied technique has proved uniquely effective
      in understanding and treating this controversial syndrome that has become central
      to psychotherapeutic concern.

PMID- 9233273
TI  - [Prolonged hospitalization for security reasons of narcissistic borderline
      adolescents: from a psychodynamic to a cognitive approach].
AB  - The notion of "mediation" has profoundly transformed clinical approaches aiming
      at a change either in knowledge, in the way of being or of behaving. The way to
      treat narcissistic-borderline adolescents in the long-term in a secure hospital
      does not escape this notion. Until now, the psychodynamic-analytical approach has
      been the only one presenting interventions in such context, and this, since many
      decades. The present article attempts to witness the evolution of the clinical
      approaches within the Quebec security-hospital milieu, and to translate in E.J.
      Young's cognitive language part of the clinical work currently done. The active
      and mediation role of the clinical intervenor (including the psychotherapist)
      constitutes the guiding line of the gradual transformation of approaches.

PMID- 9233270
TI  - [Dialectic behavioral psychotherapy for patients with borderline personality
      disorder].
AB  - Any therapist working with borderline patients knows that this is a crisis prone
      population that can be as burdening for the professional clinician as for the
      individual who experiences these intense relational episodes. Within this
      context, it is quite surprising that leaders of the behavioral approach waited
      until the beginning of the nineties before applying their technology to the
      treatment of patients diagnosed with borderline personality disorder. Linehan put
      numerous efforts to empirically demonstrate the efficiency of her newly developed
      dialectical behavior therapy, which makes it a noteworthy model. This article
      presents some historical and philosophical underpinnings of her approach,
      followed by the diagnostic criteria, the main clinical tools she advocates, the
      various dialectal dilemma, the treatment modes as well as an overview of the
      basic therapeutic strategies used in this approach.

PMID- 9233272
TI  - [Treatment of borderline personality disorder with the schema-focused approach].
AB  - The treatment of Borderline Personality Disorder has been a challenge for
      Cognitive Therapy (CT): some modifications to the CT basic model had to be
      implemented in order to intervene with BPD patients. Young's schema-focused
      approach offers an intervention model which relies on early maladaptive schemas
      and modes concepts. According to this model, the BDP presents four dysfunctional
      modes: the Abandoned Child mode, the Detached Protector mode, the Punitive Parent
      mode, the Angry Child mode. The therapist must identify the presence of these
      modes and implement therapeutic strategies specific to each of them. There are
      four different kinds of therapeutic strategies: interpersonal (therapy
      relationship), experiential, cognitive and behavioral.

PMID- 9233268
TI  - [Success and failure in the treatment of patients with borderline personality
      disorder].
AB  - This paper reviews the main treatment options for patients with borderline
      personality disorder. Pharmacological interventions are of marginal value, and
      hospitalization has not been shown to prevent suicide in this population.
      Psychodynamic psychotherapy has not been proven to be effective, but dialectical
      behavior therapy yields symptomatic improvement. Borderline patients present many
      special difficulties in therapy, particularly their chronic suicidality. Future
      developments in treatment could involve improved drug treatment combined with
      cognitive therapy.

PMID- 9233269
TI  - [The hospital's contribution to the treatment of patients with borderline
      personality disorders].
AB  - Borderline patients, because of their symptomatology are frequent users of health
      care services (mental and physical). A recent review of the literature shows that
      the authors of this article favor a treatment within the community that should be
      eclectic, on a long-term basis and with varied intensity. The hospital is part of
      the therapeutic tools available for the treatment of these patients and should
      serve to contain crisis, specify diagnosis and to prepare and reinforce a rapid
      return in their community. Exceptionally, a prolonged hospitalization (> 6
      months) would be indicated especially for adolescents.

PMID- 9233274
TI  - [Eating disorders and borderline personality disorder: what are the
      connections?].
AB  - Various forms of evidence suggest that eating disorders display a special co
      aggregation with borderline personality disorder (BPD). In this article, the
      authors review findings suggesting an apparent affinity between BPD and bulimia.
      The authors then discuss the implication of BPD on the symptomatic expression and
      response to treatment of eating disorders. Finally, they explore heuristic
      dimensions that may explain the specific association of BPD with eating
      disorders. A discussion follows proposing researchable hypotheses that may permit
      a better differentiation of processes contributing to the evolution of eating
      disorders and BPD.

PMID- 9233275
TI  - [Comparing drugs and medicines].

PMID- 9233276
TI  - [From the pharmacology of drugs to their use: formation of knowledge about
      psychotropic drugs].
AB  - Drug effects are complex events in drug users' lives. What do we know about the
      effects of major psychotropic drugs, and how have we arrived at this knowledge?
      An exercise is presented herein that assists the reader in assessing the state of
      her or his knowledge about the effects of certain psychotropic drugs. The
      exercise format allows the reader to explore how their and others' knowledge
      about psychotropic drugs are constructed, by examining cellular, organal,
      behavioral, and social levels of experience for specific drugs. Examples of
      effects for five specific drugs, identified from a variety of sources, are
      presented and described in the context of these different levels of experience.

PMID- 9233277
TI  - [The effect of family and social relations on the consumption of psychotropic
      drugs by the aged].
AB  - Psychotropic drugs are the second most commonly used medication by Quebec's
      elderly. The objective of this study is to test a theoretical model of
      psychotropic drug use in the elderly. The principal hypothesis is that the
      quality of relationships the elderly person has with others, particularly with
      his or her children, has a direct influence on his or her psychological well
      being, which, in turn, directly affects the consumption of psychotropic agents. A
      survey was conducted on a sample of 500 elderly people, aged 65-84 years, living
      at home. 31.8% of the respondents used psychotropic drugs during the three-month
      period preceding the interview. Path analysis led to the elaboration of a
      modified model for the consumption of psychotropic drugs by the elderly which
      indicates that the best predictors of consumption are both the psychological well
      being and the state of health of the individual. More elevated is the
      psychological well-being, less is the consumption of psychotropic drugs, whereas
      poor health condition increases it. The quality of an individual's social
      relationships has a direct influence on his or her psychological well-being,
      whereas family relationships are of lesser importance. Our model accounts for 13%
      of the predictors of psychotropic consumption by the elderly.

PMID- 9233278
TI  - [The tertiary effect of psychotropic drugs. Results of an anthropologic study
      conducted in southwestern France among elderly consumers].
AB  - This article presents part of the results of a research conducted in the South
      west of France on consumption by elderlies of psychotropic drugs. Two
      institutions have been chosen. The author was seeking to measure the consumption
      of psychotropic drugs before and after institutionalization, based on a medical
      questionnaire distributed to doctors working in these institutions. The author
      then examines the impact of this consumption on social relations, at home and
      within institutions, from an anthropologic perspective. Elderlies, members of
      their families, as well as doctors and other parties concerned by this
      consumption have been questioned during semi-directed interviews. Other than the
      general consumption of psychotropic drugs in the two institutions which the
      author attempts to understand the extent, only modifications in family
      relationships after the taking of drugs at home are exposed in this article.

PMID- 9233279
TI  - [Family ecology and drug consumption by the elderly: a commentary on an important
      factor ignored in research and prevention programs].
AB  - A litterature review from 1986 to 1996 on medication use by older persons
      confirms previous conclusions on studies up to 1986 (Mishara and McKim, 1989):
      there is little empirical research on the role of family members in patterns of
      medication use by elders. This article briefly summarizes studies of factors
      related to medication use and prevention programs aimed at reducing problems
      related to compliance and drug adverse reactions in older persons. We propose a
      conceptual model of the role of the family as a component of resiliency of elders
      and we suggest that family members be included in strategies for preventing the
      risks related to inappropriate use of medicines.

PMID- 9233280
TI  - [Prescription of stimulants for hyperactive children: a pilot study of incentives
      and constraints on parents, teachers and physicians].
AB  - The scientific consensus on the use of stimulants to treat "hyperactive" or ADHD
      diagnosed children amounts to recognizing a calming effect on children's
      disruptive behavior and better performance of repetitive tasks, both in the short
      term. Long-term effects remain unknown. Still, in Quebec, prescription of
      stimulants to children of welfare recipients nearly tripled between 1990 and
      1994, reaching a prevalence of 11.9%. Using a systemic model integrating three
      approaches (medicalization of deviance, political economy, and strategic
      analysis), we conceptualized the decision to prescribe as the result of
      interactions involving different actors holding unequal power and seeking to
      further their interests. We attempted to establish the defendability of this
      model by means of in-depth interviews with five parents, four primary school
      teachers and three physicians in prolonged contact with a hyperactive child
      receiving stimulant medication. Data from the interviews reveal the omnipresence
      of the medical model in the hyperactivity treatment system, although teachers
      rather than physicians appear as the engine of this medicalization. According to
      parents and physicians, teachers identify and "diagnose" children, propose the
      use of medication to parents and, in some cases, the school requires that doctors
      write a prescription. Doctors admit that medical evaluation of referred children
      is often inadequate. For their part, teachers stress the growing difficulties of
      their task and the lack of psychosocial supports in the schools. Our respondents'
      comments highlight the divergent interests of the actors involved as well as each
      actor's own perception that he or she wishes to act differently but lacks any
      real choice other than opting for medication. These limited observations should
      be validated in further studies. They suggest that the current system functions
      irrationally and that we should not expect it to act in the best interests of
      children.

PMID- 9233281
TI  - [Characteristics of physicians prescribing more psychotropic drugs to women than
      to men].
AB  - In industrialized countries, gender differences observed in health condition and
      the use of medical services appear insufficient to explain a greater consumption
      of psychotropic drugs in women than men. The authors have tested the hypothesis
      that physician prescribing patterns largely explains this observation. They
      demonstrate, using data from the Regie de l'assurance maladie du Quebec for
      people aged 65 and over, that physicians' sociodemographic and practice
      characteristics are significantly associated with the percentage of men and women
      who receive a psychotropic drug prescription in their practice.

PMID- 9233282
TI  - [Neuroleptic medication and the risk of tardive dyskinesia: a survey of
      psychiatrists and general practitioners in Quebec].
AB  - The incidence of tardive dyskinesia (TD) during the first five years of
      neuroleptic treatment of adult schizophrenic patients, may rise to 35%. Yet, the
      prevention of this iatrogenic effect remains a secondary objective for
      clinicians. This study explored how medication decisions might vary depending on
      patient characteristics and medical specialty, and to identify correlates of
      prescribing aimed at the prevention of TD. METHOD: Simulated medication decisions
      were elicited from 352 psychiatrists and 279 general practitioners in response to
      12 brief written descriptions of a male schizophrenic outpatient treated for 5
      years with 20 mg/day of haloperidol. Patient age, psychotic symptoms, signs of
      dyskinesia, and effectiveness of past treatment varied systematically in the
      descriptions. RESULTS: Every variable except patient age affected decisions. Most
      physicians reduced doses for stable patients. In cases of active psychosis,
      decisions were affected by presence of dyskinesia and treatment effectiveness.
      Psychiatrists were more likely to increase or reduce doses, general practitioners
      to change medication. Very few physicians opted to cease medication. Younger
      psychiatrists made the most prudent decisions. CONCLUSIONS: From a tardive
      dyskinesia prevention perspective, similar prescriptions to older and younger
      patients are worrying. We need to understand why physicians might believe that
      older patients require just as aggressive medication regimen as younger patients.
      Respondents within and between specialties tend make similar simulated decisions,
      but these do not necessarily reflect recommendations from controlled research on
      chronic neuroleptic treatment.

PMID- 9233283
TI  - [Pharmaceutic regulation and inadequate drug prescription in Canada: the case of
      psychotropic drugs in the 1960s and early 1970s].
AB  - The outcome of the drug approval process plays a major role in determining how
      drugs will be prescribed in Canada. The objective of this paper is to examine the
      nature of the regulatory approval process, its decisions, how these are expressed
      in pharmaceutical promotion and the ultimate impact of these factors on the
      prescribing of psychotropic drugs in general and particularly with regard to the
      benzodiazepines. There is strong circumstantial evidence that the benzodiazepines
      were approved on the basis of inadequate clinical trials resulting in these drugs
      being indicated for conditions for which they were not useful and significant
      safety issues being ignored. These deficiencies in the regulatory process were
      magnified in the advertising of these products to physicians, thus contributing
      to inappropriate prescribing in four areas: prescribing for psychosocial
      problems, overprescribing for somatic complaints, overprescribing to women and
      overprescribing for anxiety disorders. Problems in the approval process continue
      to exist and these will manifest themselves in ongoing inappropriate prescribing
      of psychotropic, and other, medications.

PMID- 9233284
TI  - [The controversy about Halcion in Great Britain: a sociological study].
AB  - This paper offers an analysis of the events surrounding the suspension of the
      licence for the widely used sleeping tablet Halcion (triazolam) by the British
      Licensing Authority in October 1991. It is argued that these events highlight a
      growing crisis in modern medical treatments and in the social relations of health
      care. This is illustrated by focusing on four elements which have contributed to
      Halcion becoming a public issue and to its suspension and subsequent banning,
      namely the claims-making activities of medical experts, the development of legal
      challenges to medicine, the role of the media and the response of the state.

PMID- 9233285
TI  - Buying or selling: a look from each side of the table.

PMID- 9233286
TI  - Contesting confidentiality.

PMID- 9233287
TI  - Technology fuels hope for patients with epilepsy.
AB  - Technological advances are making surgery a viable option for people with
      medically intractable epilepsy. More temporal lobectomies are being performed on
      young adults, fueled by recognition that many consequences of growing up with
      epilepsy can be avoided with early surgery.

PMID- 9233288
TI  - Treatment of patients with HIV in state of flux.
AB  - Protection of patients' privacy is important professionally, legally, and
      personally. Nurses must use discretion when discussing the HIV status of a
      patient with others. Treating patients with HIV or AIDS involves protection of
      staff as well as the patient.

PMID- 9233290
TI  - Out of gas. Replacing EtO sterilization.

PMID- 9233289
TI  - The nurse practitioner's role in the OR--'no substitute'.
AB  - The advanced practice nurse examines patient outcomes and ways to improve them.
      APNs maintain a continuum of care throughout the patient's entire surgical
      experience. Standards of the APN include clinical expertise and clinical
      leadership.

PMID- 9233291
TI  - The best of both worlds--'resposables'.
AB  - Managed care has brought about changes in the way surgical departments function.
      Minimally invasive surgeries are common, but costly for the surgical department.
      The use of reusable or resposable instruments can help keep costs down.

PMID- 9233292
TI  - Education bridges the gap between manufacturers and patients.
AB  - Industry representatives can pose a hazard in the OR if they do not follow
      protocols. Education can help OR staff and sales representatives understand each
      others' roles. OR safety is increased when visitors understand basics such as
      infection control.

PMID- 9233293
TI  - Where there's smoke ... Stackhouse pioneers evacuation and filtration of surgical
      smoke.

PMID- 9233294
TI  - Control of smoke from laser or electrosurgical procedures.

PMID- 9233295
TI  - Managed care and you.

PMID- 9233296
TI  - Is the profession of nursing endangered?

PMID- 9233298
TI  - RNFA programs.

PMID- 9233299
TI  - What's in a name? The evolution of universal precautions to standard precautions.
      A guide to the latest recommendations in isolation practices.
AB  - New guidelines are intended to provide infection protection to patients and
      hospital staff. Many approaches to infection prevention in hospitals have been
      considered in the past. Guidelines for infection control must be thorough,
      reasonable to apply, and protective of patients, visitors, and staff.

PMID- 9233300
TI  - How do some spell relief? S-u-r-g-e-r-y. Permanent relief for heartburn
      sufferers.
AB  - Gastroesophageal reflux disease is common, and curable with surgery. A minimally
      invasive technique offers patients with heartburn lasting relief. Laparoscopic
      technique has enhanced heartburn surgery, resulting in minimized pain and
      recovery time.

PMID- 9233301
TI  - Managing under managed care. The role of the advanced practice nurse in Surgery.
AB  - Serving as an independent practitioner expands a nurse's role in the health care
      setting. Independent nurse practitioners diagnose, treat, organize, manage, and
      communicate. Having a nurse practitioner in the OR helps provide continuity of
      patient care.

PMID- 9233302
TI  - Sensitive beings locked in immobile bodies.
AB  - Consciousness during sedation has a long and well documented history. Awareness
      during anesthesia has been reported and is terrifying for the patient. Surgical
      staff must anticipate the possibility that the sedated patient is conscious.

PMID- 9233303
TI  - RNs: conscious sedation providers?

PMID- 9233304
TI  - The nurse anesthetist: issues in rural health care.
AB  - Nurse anesthetists in rural regions must find creative solutions to challenges.
      Patient abandonment and legal issues can be important for the rural anesthesia
      provider to consider in some emergencies. Rural hospitals must develop protocols
      to help nurses and nurse anesthetists deal with emergency situations.

PMID- 9233305
TI  - Airway adventures in Africa.
AB  - Difficult airway management may challenge any anesthesia provider. A clear and
      protected airway must be maintained even in difficult intubations. In challenging
      cases, careful preoperative assessment and good communication with colleagues are
      required.

PMID- 9233306
TI  - Lynda's story. Campaigning for health care worker safety.

PMID- 9233307
TI  - Your rights as an employee (Part II).

PMID- 9233308
TI  - Guidelines for managing HIV infection.

PMID- 9233309
TI  - Bringing epilepsy out of the shadows.

PMID- 9233310
TI  - Five years down the road from Rio.

PMID- 9233311
TI  - Making the diagnosis of asthma.

PMID- 9233312
TI  - Career guidance for doctors.

PMID- 9233313
TI  - UK government proposes health action zones.

PMID- 9233314
TI  - Liver cancer in Taiwan falls after universal hepatitis B vaccination.

PMID- 9233315
TI  - Hong Kong bans tobacco advertising.

PMID- 9233316
TI  - Identifying sentinel node could reduce surgery in breast cancer.

PMID- 9233317
TI  - Germany passes new transplant law.

PMID- 9233318
TI  - American Diabetes Association calls for testing all those over 45.

PMID- 9233319
TI  - Dietary pattern and 20 year mortality in elderly men in Finland, Italy, and The
      Netherlands: longitudinal cohort study.
AB  - OBJECTIVE: To investigate the association of dietary pattern and mortality in
      international data. DESIGN: Cohort study with 20 years' follow up of mortality.
      SETTING: Five cohorts in Finland, the Netherlands, and Italy. SUBJECTS:
      Population based random sample of 3045 men aged 50-70 years in 1970. MAIN OUTCOME
      MEASURES: Food intake was estimated using a cross check dietary history. In this
      dietary survey method, the usual food consumption pattern in the 6-12 months is
      estimated. A healthy diet indicator was calculated for the dietary pattern, using
      the World Health Organisation's guidelines for the prevention of chronic
      diseases. Vital status was verified after 20 years of follow up, and death rates
      were calculated. RESULTS: Dietary intake varied greatly in 1970 between the three
      countries. In Finland and the Netherlands the intake of saturated fatty acids and
      cholesterol was high and the intake of alcohol was low; in Italy the opposite was
      observed. In total 1796 men (59%) died during 20 years of follow up. The healthy
      diet indicator was inversely associated with mortality (P for trend < 0.05).
      After adjustment for age, smoking, and alcohol consumption, the relative risk in
      the group with the healthiest diet indicator compared with the group with the
      least healthy was 0.87 (95% confidence interval 0.77 to 0.98). Estimated relative
      risks were essentially similar within each country. CONCLUSIONS: Dietary intake
      of men aged 50-70 is associated with a 20 year, all cause mortality in different
      cultures. The healthy diet indicator is useful in evaluating the relation of
      mortality to dietary patterns.

PMID- 9233320
TI  - Substance use in remand prisoners: a consecutive case study.
AB  - OBJECTIVES: To determine the prevalence of drug and alcohol use among newly
      remanded prisoners, assess the effectiveness of prison reception screening, and
      examine the clinical management of substance misusers among remand prisoners.
      DESIGN: A consecutive case study of remand prisoners screened at reception for
      substance misuse and treatment needs and comparison of findings with those of
      prison reception screening and treatment provision. SETTING: A large adult male
      remand prison (Durham). SUBJECTS: 548 men aged 21 and over awaiting trial. MAIN
      OUTCOME MEASURES: Prevalence of substance misuse; treatment needs of substance
      misusers; effectiveness of prison reception screening for substance misuse;
      provision of detoxification programmes. RESULTS: Before remand 312 (57%) men were
      using illicit drugs and 181 (33%) met DSM-IV drug misuse or dependence criteria;
      177 (32%) men met misuse or dependence criteria for alcohol. 391 (71%) men were
      judged to require help directed at their drug or alcohol use and 197 (36%) were
      judged to require a detoxification programme. The prison reception screen
      identified recent illicit drug use in 131 (24%) of 536 men and problem drinking
      in 103 (19%). Drug use was more likely to be identified by prison screening if an
      inmate was using multiple substances, using opiates, or had a diagnosis of abuse
      or dependence. 47 (9%) of 536 inmates were prescribed treatment to ease the
      symptoms of substance withdrawal. CONCLUSIONS: The prevalence of substance misuse
      in newly remanded prisoners is high. Prison reception health screening
      consistently underestimated drug and alcohol use. In many cases in which
      substance use is identified the quantities and numbers of different substances
      being used are underestimated. Initial management of inmates identified by prison
      screening as having problems with dependence producing substances is poor. Few
      receive a detoxification programme, so that many are left with the option of
      continuing to use drugs in prison or facing untreated withdrawal.

PMID- 9233322
TI  - Physiotherapy for patients with soft tissue shoulder disorders: a systematic
      review of randomised clinical trials.
AB  - OBJECTIVE: To assess the effectiveness of physiotherapy for patients with soft
      tissue shoulder disorders. DESIGN: A systematic computerised literature search of
      Medline and Embase, supplemented with citation tracking, for relevant trials with
      random allocation published before 1996. SUBJECTS: Patients treated with
      physiotherapy for disorders of soft tissue of the shoulder. MAIN OUTCOME
      MEASURES: Success rates, mobility, pain, functional status. RESULTS: Six of the
      20 assessed trials satisfied at least five of eight validity criteria. Assessment
      of methods was often hampered by insufficient information on various validity
      criteria, and trials were often flawed by lack of blinding, high proportions of
      withdrawals from treatment, and high proportions of missing values. Trial sizes
      were small: only six trials included intervention groups of more than 25
      patients. Ultrasound therapy, evaluated in six trials, was not shown to be
      effective. Four other trials favoured physiotherapy (laser therapy or
      manipulation), but the validity of their methods was unsatisfactory. CONCLUSIONS:
      There is evidence that ultrasound therapy is ineffective in the treatment of soft
      tissue shoulder disorders. Due to small trial sizes and unsatisfactory methods,
      evidence for the effectiveness of other methods of physiotherapy is inconclusive.
      For all methods of treatment, trials were too heterogeneous with respect to
      included patients, index and reference treatments, and follow up to merit valid
      statistical pooling. Future studies should show whether physiotherapy is superior
      to treatment with drugs, steroid injections, or a wait and see policy.

PMID- 9233321
TI  - Harm reduction measures and injecting inside prison versus mandatory drugs
      testing: results of a cross sectional anonymous questionnaire survey. The
      European Commission Network on HIV Infection and Hepatitis in Prison.
AB  - OBJECTIVES: (a) To determine both the frequency of injecting inside prison and
      use of sterilising tablets to clean needles in the previous four weeks; (b) to
      assess the efficiency of random mandatory drugs testing at detecting prisoners
      who inject heroin inside prison; (c) to determine the percentage of prisoners who
      had been offered vaccination against hepatitis B. DESIGN: Cross sectional willing
      anonymous salivary HIV surveillance linked to a self completion risk factor
      questionnaire. SETTING: Lowmoss prison, Glasgow, and Aberdeen prison on 11 and 30
      October 1996. SUBJECTS: 293 (94%) of all 312 inmates at Lowmoss and 146 (93%) of
      all 157 at Aberdeen, resulting in 286 and 143 valid questionnaires. MAIN OUTCOME
      MEASURES: Frequency of injecting inside prison in the previous four weeks by
      injector inmates who had been in prison for at least four weeks. RESULTS: 116
      (41%) Lowmoss and 53 (37%) Aberdeen prisoners had a history of injecting drug use
      but only 4% of inmates (17/395; 95% confidence interval 2% to 6%) had ever been
      offered vaccination against hepatitis B. 42 Lowmoss prisoners (estimated 207
      injections and 258 uses of sterilising tablets) and 31 Aberdeen prisoners (229
      injections, 221 uses) had injected inside prison in the previous four weeks. The
      prisons together held 112 injector inmates who had been in prison for more than
      four weeks, of whom 57 (51%; 42% to 60%) had injected in prison in the past four
      weeks; their estimated mean number of injections was 6.0 (SD 5.7). Prisoners
      injecting heroin six times in four weeks will test positive in random mandatory
      drugs testing on at most 18 days out of 28. CONCLUSIONS: Sterilising tablets and
      hepatitis B vaccination should be offered to all prisoners. Random mandatory
      drugs testing seriously underestimates injector inmates' harm reduction needs.

PMID- 9233323
TI  - Prevalence of HIV and injecting drug use in men entering Liverpool prison.

PMID- 9233324
TI  - Incidence and outcome of bleeding before the 20th week of pregnancy: prospective
      study from general practice.
AB  - OBJECTIVE: To estimate the miscarriage rate in a cohort of pregnant women and the
      final outcome of pregnancy. DESIGN: Two year prospective community study.
      SETTING: Women registered with four semirural practices at one health centre.
      SUBJECTS: 626 pregnant women from a population 21448, 5140 of whom were women
      aged 15-44 years. MAIN OUTCOME MEASURES: Vaginal bleeding and outcome of
      pregnancy. RESULTS: 76 of the 89 women with an unwanted pregnancy requested a
      termination. In the 550 ongoing pregnancies bleeding occurred before the 20th
      week in 117 (21%), and 67 (12%) ended in miscarriage. The risk of miscarriage was
      not significantly increased after a miscarriage in the previous pregnancy (11
      (15%) women had miscarriage v 55 (12%) women who had not had miscarriage) who had
      previously had a live birth). Of the 117 women with bleeding, 64 were not
      admitted to hospital by the general practitioner; 42 of these women had an
      ultrasound examination at the health centre and 19 subsequently miscarried at
      home. In hospital 41 of 46 women who miscarried had evacuation of the uterus.
      CONCLUSIONS: Bleeding occurred in one fifth of recognised pregnancies before the
      20th week and over half of these miscarried. Treatment of women with miscarriage
      at home means current statistics on miscarriage in Britain are missing many
      cases.

PMID- 9233325
TI  - Predicting stress in general practitioners: 10 year follow up postal survey.

PMID- 9233326
TI  - A randomised controlled trial of feedback to general practitioners of their
      prophylactic aspirin prescribing.

PMID- 9233327
TI  - Management of abnormal bleeding in women receiving hormone replacement therapy.

PMID- 9233328
TI  - ABC of mental health. Depression.

PMID- 9233329
TI  - Personal paper: how to get the best health outcome for a given amount of money.

PMID- 9233330
TI  - Disease management.
AB  - The disease management approach to patient care seeks to coordinate resources
      across the healthcare delivery system. The growing interest in evidence based
      medicine and outcomes, and a commitment to integrated care across the primary,
      secondary, and community care sectors, all contribute to making disease
      management an attractive idea. A combination of patient education, provider use
      of practice guidelines, appropriate consultation, and supplies of drugs and
      ancillary services all come together in the disease management process. But its
      effectiveness is largely untested, so evaluation is essential.

PMID- 9233331
TI  - Britain's first minister of public health. National centre for public health is
      needed.

PMID- 9233332
TI  - Britain's first minister of public health. National public health research and
      development programme is needed.

PMID- 9233333
TI  - Britain's first minister of public health. White paper on public health is needed
      to give coherent approach across all sectors.

PMID- 9233334
TI  - No consensus seems to exist about when caesarean section is medically indicated.

PMID- 9233335
TI  - Fatal methadone overdose. Drug services in Manchester were unfairly accused.

PMID- 9233336
TI  - Fatal methadone overdose. Sloppy prescribing cannot be totally blamed for deaths
      from methadone overdose.

PMID- 9233337
TI  - Patients receive an inadequate dose of antidepressants for an inadequate period.

PMID- 9233338
TI  - Advice on long-term corticosteroid treatment may be misleading.

PMID- 9233339
TI  - Is it time to stop searching for MRSA? Follow up screening within the community
      needs clarification.

PMID- 9233340
TI  - Is it time to stop searching for MRSA? Selective screening for MRSA should be
      considered.

PMID- 9233341
TI  - Is it time to stop searching for MRSA? Healthcare workers are at risk from
      policies for controlling MRSA.

PMID- 9233342
TI  - Is it time to stop searching for MRSA? Isolating patients with MRSA can have long
      term implications.

PMID- 9233343
TI  - Is it time to stop searching for MRSA? Practical guidelines are needed for
      healthcare workers.

PMID- 9233344
TI  - Is it time to stop searching for MRSA? Risk analysis can identify those patients
      needing isolation.

PMID- 9233345
TI  - Is it time to stop searching for MRSA? Constant vigilance is needed to halt the
      emergence of resistance to vancomycin.

PMID- 9233346
TI  - Is it time to stop searching for MRSA? Basic hygiene should help contain MRSA.

PMID- 9233347
TI  - Is it time to stop searching for MRSA? Environmental hygiene is an important part
      of control.

PMID- 9233349
TI  - Benefit of using polymerase chain reaction to test blood donations will be
      considerable.

PMID- 9233348
TI  - Should oral contraceptive users be screened for factor V Leiden? Oral
      contraceptives are not the only effective contraceptives.

PMID- 9233350
TI  - Local research ethics committees. BMA's advice about approval of clinical audit
      studies is confusing.

PMID- 9233351
TI  - Local research ethics committees. National research ethics committee is needed.

PMID- 9233352
TI  - Three quarters of one French prison population needed immunisation against
      hepatitis B.

PMID- 9233353
TI  - Mistake in report: hepatitis B vaccination for drug misusers is recommended.

PMID- 9233357
TI  - Children have rights to medicines.

PMID- 9233354
TI  - GPs need training in care programme approach more than in supervised discharge.

PMID- 9233358
TI  - Neurodevelopment in offspring of hairdressers.
AB  - The hypothesis that intrauterine exposure to hairdressers' chemicals adversely
      affects neurodevelopment of the offspring was investigated. Neurodevelopmental
      characteristics were analysed using a historical cohort study of reproductive
      disorders among hairdressers in The Netherlands. Because exposure in hair salons
      to agents toxic to reproductive processes might have changed over time, two
      specific study periods were examined: from 1986 to 1988 and from 1991 to 1993.
      Nine thousand hairdressers and 9000 clothing sales clerks (referent group) who
      were in the reproductive age in the defined study periods were selected by the
      trade association for service jobs. Frequency matching assured comparability with
      regard to age. All women were invited by mail to complete a short self
      administered questionnaire on their reproductive history, including questions on
      the ages of their child at the times of the first words, first sentences, and
      first steps, and the occurrence of seizures during fever. The results showed that
      in 1986 to 1988 more children of hairdressers started speaking their first words
      after 15 months and their first sentences after 24 months. For 1991 to 1993 no
      increased risks of these outcomes were found. Seizures during fever had occurred
      more often among children of hairdressers in 1986 to 1988, and in 1991 to 1993,
      especially when women had been working until maternity leave. Although the
      quality of the data in this explorative study requires careful interpretation,
      the consistent results seem to indicate adverse effects on neurodevelopment among
      offspring of hairdressers in the earlier years (1986 to 1988). In the later years
      the effect seemed to be disappearing. However, these findings should be confirmed
      in more detailed studies.

PMID- 9233359
TI  - MRI findings in patients with spastic cerebral palsy. I: Correlation with
      gestational age at birth.
AB  - The authors studied MR images of the brain in 152 patients, aged 1 to 19 years
      (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals
      in Japan in 1993 and 1994. The relation was studied between the patients'
      gestational age at birth and their MRI findings, including the severity of
      periventricular leukomalacia (PVL) seen on MRI. In 119 of these patients, the CP
      was thought to be due to acquired, destructive brain injury. PVL was seen in 90
      and posthemorrhagic porencephaly in 11. These preterm-type brain injuries were
      observed often in patients who had been born preterm but were also seen in those
      born at term. Fullterm-type border-zone infarct, bilateral basal ganglia-thalamic
      lesion, subcortical leukomalacia, and multicystic encephalomalacia were seen in
      9, 14, 7, and 3 patients, respectively; these term-type brain injuries were
      observed only in patients born at or near term. Of the patients with PVL, 90% had
      been born preterm. Severe PVL was common in the patients whose gestational ages
      at birth were between 25 and 32 weeks; all patients with PVL who had been born at
      term had only mild PVL. The authors concluded that MRI findings for patients with
      spastic CP are closely correlated with gestational age.

PMID- 9233360
TI  - MRI findings in patients with spastic cerebral palsy. II: Correlation with type
      of cerebral palsy.
AB  - The authors studied MR images of the brain in 152 patients, aged 1 to 19 years
      (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals
      in Japan in 1993 and 1994. Eighty-one patients had diplegia, 45 had quadriplegia,
      and 26 had hemiplegia. Of patients with diplegia, 72 had periventricular
      leukomalacia (PVL) and very few had other types of lesions. In patients with
      quadriplegia, three main types of brain lesions were observed: PVL in 12
      patients, term-type brain injury in 22, and brain anomaly in 10. In the 26
      patients with hemiplegia, 17 had a unilateral lesion (rare in patients with
      diplegia and quadriplegia), and bilateral lesions were seen in seven others.

PMID- 9233361
TI  - Early cerebral proton MRS and neurodevelopmental outcome in infants with cystic
      leukomalacia.
AB  - The present study tested the hypothesis that proton magnetic resonance
      spectroscopy (1H-MRS) predicted neurodevelopmental outcome in infants with cystic
      leukomalacia (CL). Nineteen infants with CL (grade 2, N = 7; grade 3, N = 7;
      grade 4, N = 5), graded according to the authors' classification, were examined
      at corrected ages of mean 1.5 +/- 2.1 SD weeks. 1H-MRS of the basal ganglia and
      the periventricular white matter was performed. Two infants died, 16 had an
      adverse neurodevelopmental outcome and one was normal at follow-up. N
      acetylaspartate (NAA):choline (Cho) ratios were mean 1.12 +/- 0.19 (SD) (grade
      2), mean 0.95 +/- 0.11 (SD) (grade 3), and mean 0.71 +/- 0.13 (SD) (grade 4).
      These differences are significant (P < 0.01, ANOVA). NAA:Cho ratios showed a
      positive correlation with developmental quotient (DQ) at the age of > or = 1 year
      (P < 0.05). In 13 infants lactate (Lac) was found. Lac:NAA ratios showed a
      negative correlation with NAA:Cho ratios, but not with DQ. We conclude that a low
      NAA:Cho ratio predicted a poor outcome, whereas some infants developed
      unfavourably despite a normal NAA:Cho ratio. We speculate that partial volume
      effects might explain this observation.

PMID- 9233362
TI  - Febrile seizures in a south Indian district: incidence and associations.
AB  - One thousand four hundred and three children participated in a home-based survey
      of psychiatric disorders in 8- to 12-year-old children in Calicut District,
      Kerala, India. One thousand one hundred and ninety-two consecutive children
      underwent neurological and psychometric assessments. The projected number of
      children with a history of febrile seizures was 120 giving a lifetime incidence
      of 10.1%. Recurrent febrille seizures predominated and these were strongly
      associated with a history of perinatal adversity. Febrile seizures were
      independently association with indices of infective illness and mothers'
      education. Epilepsy developed in 2.7% of children with febrile seizures, but no
      evidence was found that febrile seizures had adverse intellectual or behavioural
      sequelae.

PMID- 9233364
TI  - Taste and smell in familial dysautonomia.
AB  - Familial dysautonomia (FD) is one of the classic diseases characterised by taste
      and smell abnormalities. However, these typical features are based on data
      obtained from two separate crude studies published in 1964. In the present study
      psychophysical-cognitive and reflex-like facial-behavioral responses to taste and
      smell, in nine patients with FD and 15 healthy controls, were recorded. Five
      taste stimulants were presented to both study groups, while a selection of common
      household odors was used for FD patients only. The patients with FD showed a
      markedly higher incidence of recognition failures for salty, bitter, sweet, and
      water stimuli than the controls, but rate of recognition of sour stimuli was
      almost identical in the two groups. Estimates by the subjects on a hedonic scale
      of 0 to 10 and facial display in FD indicated a relatively normal sensitivity to
      sour stimuli and to a lesser extent to bitter stimuli. Water, sweet, and salty
      stimuli evoked non-discriminatory responses. These findings indicate specific
      dyageusia rather than general ageusia. Smell was found to be normal. In children
      with taste and smell impairment, a systematic evaluative approach may help in
      planning palatable diets for adequate and comfortable nutrition.

PMID- 9233363
TI  - Neuroradiological assessment of visuoperceptual disturbance in children with
      spina bifida and hydrocephalus.
AB  - The intellectual status of twelve children with spina bifida and hydrocephalus
      was evaluated. Seven children were considered to have verbal and non-verbal skill
      discrepancies. It was considered that the Verbal IQ-Performance IQ score by WISC
      R could be used as an index of their visuoperceptual disturbance. The disturbance
      was closely related to the morphological characteristics of the lateral
      ventricles on cerebral MRI. The ratio of the areas of the posterior horns to the
      anterior horns (P:A) showed a negative correlation with visuoperceptual ability.
      The visual pathway, visual cortex, and the ventral system were thus considered to
      be the sites of the affected lesions. From P:A changes with time, it was evident
      that adequate shunting would prevent the perceptual disturbance.

PMID- 9233365
TI  - The predictive value of cranial ultrasound and of somatosensory evoked potentials
      after nerve stimulation for adverse neurological outcome in preterm infants.
AB  - Thirty-nine preterm infants were studied to compare the predictive value of
      somatosensory evoked responses (SEPs) following median-nerve and posterior tibial
      nerve stimulation with the predictive value of cranial ultrasound. With regard to
      the SEP, a normal median-nerve response was by no means a guarantee of a normal
      outcome. A normal posterior tibial-nerve response, however, almost guaranteed a
      normal outcome, but the test was very time consuming and the number of false
      positive responses was high (sensitivity 95.6%, specificity 50%). The presence of
      parenchymal involvement, either due to a haemorrhage or cystic leukomalacia
      predicted cerebral palsy with a sensitivity of 95.6% and specificity of 68.5%.
      The combination of an abnormal posterior tibial response and the presence of
      parenchymal brain lesions had the best predictive value with a sensitivity of
      91.3% and a specificity of 81.2%. These results show that, although posterior
      tibial-nerve responses have a better predictive value than median-nerve
      responses, these values were lower than that of cranial ultrasound. The best
      prediction was obtained when a combination of posterior-tibial responses and
      cranial ultrasound was used.

PMID- 9233366
TI  - How do children who are clumsy remember modelled movements?
AB  - The ability of children who are clumsy, and of control children, to reproduce
      short sequences of simple movements immediately, and after a delay of 15 seconds,
      was examined. Four kinds of interference were introduced during the delay. These
      were visual or kinaesthetic each with either a high or a low spatial component.
      The reproductions of the movements by clumsy children were inferior to those by
      control children only after visual interference with a high spatial involvement.
      It was concluded that the memory of clumsy children for modelled movements is
      more dependent on visuospatial rehearsal than is the memory of normal children.

PMID- 9233368
TI  - Treatment of multiple sleep problems in children with developmental disabilities:
      faded bedtime with response cost versus bedtime scheduling.
AB  - Sleep problems are a common concern for persons with mental retardation and
      severe behavior problems, yet few empirically validated treatment options exist.
      In the current investigation, the efficacy of a faded bedtime with response cost
      treatment was compared with a bedtime scheduling procedure in treating the
      multiple sleep problems of two groups of children with mental retardation, sleep
      problems, and other severe behavior problems. Faded bedtime with response cost
      (FBRC) consisted of systematic delay of bedtime, removal from bed if sleep was
      not initiated within 15 minutes (response cost), and a fading procedure to
      gradually advance the bedtime. The bedtime scheduling procedure consisted of a
      consistent sleep and wake time and prevention of daytime sleep. The sleep of
      children in the FBRC group improved significantly more than the sleep of children
      in the bedtime scheduling group. Results are discussed in terms of behavioral and
      biological mechanisms which may contribute to the efficacy of FBRC.

PMID- 9233367
TI  - Tactile recognition in infantile nephropathic cystinosis.
AB  - Previous studies have demonstrated that individuals with cystinosis, an inherited
      metabolic disorder, have difficulty processing visual information, and may be
      selectively impaired in the ability to mentally rotate figures, despite having
      normal IQs and normal primary sensory function. In our novel task-the 'Black Box'
      subjects identified objects solely by feeling the contours. Twenty-three subjects
      with cystinosis, aged 4 to 34 years, were individually matched with controls on
      age, sex, handedness, and test form. Subjects with cystinosis performed
      significantly worse in identifying objects than did controls. In addition, when
      only subjects over 7 years of age were included, those with cystinosis took
      significantly longer to correctly identify objects than did controls. Our
      findings suggest that individuals with cystinosis have difficulty with tactile
      recognition of common objects. These results support the hypothesis that a
      genetic disorder may have specific behavioral correlates.

PMID- 9233369
TI  - Spinal muscular atrophy of childhood: genetics.

PMID- 9233371
TI  - 'Intravenous immunoglobulin treatment in childhood Guillain-Barre syndrome'.

PMID- 9233370
TI  - Monocular vision loss can cause bilateral nystagmus in young children.

PMID- 9233372
TI  - Induction of glutathione depletion, p53 protein accumulation and cellular
      transformation by tetrachlorohydroquinone, a toxic metabolite of
      pentachlorophenol.
AB  - Glutathione (GSH) conjugate formation with tetrachlorohydroquione (TCHQ) and the
      GSH content in vivo were measured by capillary zone electrophoresis. A more than
      60% depletion of GSH content was found in liver tissue of mice treated with TCHQ.
      In addition, p53 protein accumulation and DNA fragmentation was induced by TCHQ.
      A two-stage model of chemical transformation of mouse embryonic fibroblasts was
      used to elucidate the transformation activity of TCHQ in vitro, and a 33% foci
      formation efficiency was found at the concentration of 5 microM. GSH depletion
      caused by TCHQ could abolish the protective ability of the cell against reactive
      oxygen species provided by GSH. When DNA was damaged, p53 protein accumulated in
      the nucleus and, in the case of severe damage, initiated apoptosis. TCHQ's
      ability to cause GSH depletion and DNA damage may play a role in the cytotoxic
      and genotoxic properties of its metabolic precursor, PCP.

PMID- 9233373
TI  - Modulation of glutathione conjugation in vivo: how to decrease glutathione
      conjugation in vivo or in intact cellular systems in vitro.
AB  - Glutathione conjugation is involved in detoxification and toxification of a
      variety of electrophilic substrates. Thus it plays a major role in protection
      against reactive intermediates. At the same time this conjugation may cause
      resistance of tumor cells against certain cytostatics. In this review the methods
      available to decrease glutathione conjugation in vivo are discussed. So far the
      only in vivo active inhibitors of glutathione S-transferases are ethacrynic acid
      and a number of glutathione-derived structures; the latter seem very promising
      for further development. For (chronic) glutathione-depletion, buthionine
      sulfoximine is most effective, and surprisingly safe in clinical studies.
      Diethylmaleate can be used for acute depletion. Inhibition of glutathione
      transferases offers advantages over glutathione depletion as a method of
      decreasing glutathione conjugation since inhibition may be accomplished without
      changing the activities of other glutathione-dependent reactions in the cell.
      However, clinically safe, in vivo effective and isoenzyme-selective glutathione S
      transferase inhibitors have not yet been developed.

PMID- 9233374
TI  - Kinetics of the conjugation of aniline mustards with glutathione and thiosulfate.
AB  - The rates of the non-enzymatic conjugation of the substituted aniline mustards,
      melphalan, chlorambucil and p-(N,N-bis(2-chloroethyl))toluidine with glutathione
      and thiosulfate were determined using nuclear magnetic resonance spectroscopy.
      Using this method, the disappearance of drug and the formation of both the mono
      thioether and bis-thioether conjugates can be monitored directly. For glutathione
      conjugation, the rate constants for the formation of the first and second
      aziridinium intermediates were similar. With thiosulfate conjugation, the rate
      constant for the formation of the first aziridinium intermediate is greater than
      the rate constant for the formation of the second aziridinium. This demonstrates
      that the type of nucleophile has a significant influence on the overall
      alkylating activity of these bifunctional mustards. The bisthioether adduct
      formed from the reaction between p-(N,N-bis([2-13C]-2-chloroethyl))toluidine and
      glutathione and thiosulfate can be identified and scrambling of the 13C label in
      the product provides strong evidence that the alkylation must occur through an
      aziridinium intermediate.

PMID- 9233375
TI  - Regulation of hepatic CYP1A isozymes by piperonyl butoxide and acenaphthylene in
      the mouse.
AB  - The regulation of CYP1A1 and CYP1A2 isozymes by piperonyl butoxide (PBO) and
      acenaphthylene (ACN) was studied in the liver of male C57BL/6 and DBA/2 mice.
      These two cytochrome P450 genes are known to be regulated by the aromatic
      hydrocarbon-responsive receptor (AHR); however, it has been suggested that CYP1A2
      is also induced by an AHR-independent mechanism. In this study, PBO induced
      hepatic CYP1A1 considerably more in C57BL/6 (Ahrb-I) than in DBA/2 (Ahrd) mice.
      In addition, the superinduction of CYP1A1 in wildtype hepa1c1c7 cells, which is
      AHR-dependent, resulted from PBO and cycloheximide treatment of the cells. In
      other studies in this laboratory using AHR knock-out (AHR-/-) mice, a hybrid of
      129/SV and C57BL/6 strains, no induction of CYP1A1 occurred with PBO or ACN. [D.
      Y. Ryu, P.E. Levi, P. Fernandez-Salguero, F.J. Gonzalez, E. Hodgson, Mol.
      Pharmacol., 50 (1996) 443-446.] ACN, however, did not induce CYP1A1 under the
      experimental conditions used. These results suggest that PBO, but not ACN,
      induces CYP1A1 through a weak activation of AHR. On the other hand, hepatic
      CYP1A2 mRNA and hnRNA were induced by PBO in both C57BL/6 and DBA/2 strains, but
      were not induced by ACN, a strong inducer of CYP1A2 in the B6C3F1 strain.
      However, both PBO and ACN induced CYP1A2 in AHR-/- mice. It is assumed,
      therefore, that the transcriptional induction of CYP1A2 by PBO and ACN is AHR
      independent. In addition, the induction of CYP1A2 by ACN depends upon the strain
      of mice. Immunohistochemical studies for CYP1A1/CYP1A2 apoproteins showed that
      PBO induced CYP1A1/CYP1A2 around the central veins as did 3-methylcholanthrene (3
      MC). The induction of CYP1A1/CYP1A2 by ACN, however, was not observed, consistent
      with the northern blot results.

PMID- 9233376
TI  - Effects of N-nitrosodimethylamine on glutathione levels during development of
      chick-embryo.
AB  - Glutathione content in the liver, kidney and eye of chick embryo increased during
      development, having the maximum at day 17 after incubation of eggs. Activity of
      enzymes involved in glutathione metabolism changed during development. gamma
      Glutamyltransferase activity increased gradually until day 17 in the liver and
      eye, but decreased thereafter, while the enzyme activity increased continuously
      in the kidney. Glutathione reductase and glutathione peroxidase activities did
      not change significantly during development. Administration of N
      nitrosodimethylamine (NDMA) to the fertile eggs 2 days after incubation resulted
      in an increase of glutathione levels in the liver and kidney at a dose of 0.01
      mmol NDMA/egg, but the effect was not significant for glutathione levels by
      increasing the dose of NDMA. Decrease in viability and increase in formation of
      thiobarbituric acid (TBA) reactive substance were observed in the liver and
      kidney by administration of NDMA at 0.1 mmol/egg. By administration of buthionine
      sulfoximine (BSO) alone, viability and glutathione levels were decreased and TBA
      reactive substance was increased in the liver. Fatal toxicity of NDMA was
      observed especially when BSO was administered together with NDMA. These results
      indicate that glutathione plays an important role in protecting chick embryos
      against toxic effects induced by administration of NDMA.

PMID- 9233377
TI  - Pathobiology of lipopolysaccharide.
AB  - Lipopolysaccharide is a component of the gram-negative bacterial cell wall that
      is responsible for 25,000-50,000 deaths in the United States each year. The
      sequelae of gram-negative infection and septicemia leading to death include
      fever, hypotension with inadequate tissue perfusion, and disseminated
      intravascular coagulation. It is clear that different cell types respond
      differently to lipopolysaccharide. Furthermore, various autacoids and cytokines
      are released that can affect cellular function even in cell types that do not
      recognize lipopolysaccharide. Despite advances made in the etiology of septic
      shock and organ failure, therapy is still for the most part supportive and
      largely ineffective. The aim of this review is to summarize the current
      understanding of the role of lipopolysaccharide in the development of septicemia
      by examining signal transduction and therapeutic approaches.

PMID- 9233378
TI  - Hair selenium as a monitoring tool for occupational exposures in relation to
      clinical profile.
AB  - Nineteen workers exposed to low levels of selenium (0.047-0.202 mg/m3 air) along
      with 15 control subjects were studied for clinical, hematological, radiological,
      and neurobehavioral variables in relation to selenium concentration in hair. The
      levels of selenium in the hair of exposed subjects (1.44 +/- 0.37 micrograms/g)
      were significantly higher than those of control subjects (0.78 +/- 0.18
      microgram/g). The levels of selenium in the hair of 22 nonvegetarian subjects
      were found to be significantly higher as compared to 12 vegetarian subjects.
      Complaints of weakness and/or fatigue were found to be more prevalent in the
      exposed subjects. The study holds promise that hair selenium may be used as a
      monitoring tool for low-level occupational exposure to selenium.

PMID- 9233379
TI  - Effect of environmental conditions on the penetration of benzene through human
      skin.
AB  - The in vitro penetration of [14C]benzene through freshly prepared human skin was
      examined under a variety of skin conditions associated with swimming and bathing.
      The experimental system utilized a recirculating donor solution and a flow
      through receiver solution, and was modified to accommodate the analysis of
      volatiles. The permeability coefficient of 0.14 cm/h under standard conditions at
      26 degrees C was found to increase to 0.26 cm/h at 50 degrees C and decrease to
      0.10 cm/h at 15 degrees C. Storage of the skin at- 20 degrees C did not affect
      the penetration of benzene. Application of baby oil, moisturizer, or insect
      repellant to the skin before exposure under standard conditions did not affect
      the flux of benzene, but a significant increase was observed when the skin was
      pretreated with sunscreen (permeability coefficient 0.24 cm/h). These results
      suggest that risk assessment or exposure modeling for benzene and other
      environmental contaminants should account for appropriate changes in the
      environmental conditions when considering the dermal route of exposure.

PMID- 9233381
TI  - Effects of inducers and inhibitors on the microsomal metabolism of styrene to
      styrene oxide in mice.
AB  - Styrene is both hepatotoxic and pneumotoxic in mice, with non-Swiss albino (NSA)
      mice being more sensitive than Swiss (CD-1) mice. The toxicity of styrene is
      potentiated by treatment with phenobarbital, beta-naphthoflavone, or pyridine.
      Since the toxicity of styrene is generally associated with its metabolism to
      styrene oxide (SO), the formation of SO by hepatic and pulmonary microsomes of
      NSA and CD-1 mice was measured to examine correlations with toxicity. Both
      enantiomers of SO were quantified since the R-SO enantiomer is more toxic than
      the S-SO enantiomer. No strain differences in rates of styrene metabolism or
      enantiomeric ratio were observed in control mice or mice treated with inducers.
      Pyridine, an inducer of CYP2E1, increased S-SO but not R-SO formation in liver.
      Phenobarbital, an inducer of CYP2B, increased the production of both enantiomers.
      beta-Naphthoflavone, an inducer of CYP1A, had no effect. None of the inducers had
      any effect in lung. Addition of the CYP2E1 inhibitor diethyldithiocarbamate
      decreased the formation of both enantiomers in both tissues from control mice,
      whereas 5-phenyl-1-pentyne (an inhibitor of CYP2F2) inhibited metabolism
      primarily in lung. In both control and phenobarbital-treated mice, SKF525A
      inhibited both R-SO and S-SO in liver but only S-SO in lung. Thus there are
      tissue differences in metabolism and susceptibility to induction and inhibition
      but no strain differences in metabolism to explain differences in susceptibility
      to styrene-induced toxicity.

PMID- 9233380
TI  - Effect of dosing vehicle on the hepatotoxicity of CCl4 and nephrotoxicity of
      CHCl3 in rats.
AB  - There are conflicting results in the literature concerning the effect of gavage
      vehicle, corn oil (CO) versus aqueous suspension, on the toxicity of haloalkanes.
      The purpose of our study was to assess the influence of oral dosing vehicle on
      the acute hepatotoxicity of CCl4 and nephrotoxicity of CHCl3. Male Sprague-Dawley
      rats, fed ad libitum, were treated (po) with single doses of CCl4 or CHCl3 using
      corn oil (CO), or an aqueous preparation (5%) of Emulphor (EL620) or Tween-85 (Tw
      85) as vehicle (10 ml/kg). Rats were killed 48 h after treatment. Blood was
      collected for plasma alanine aminotransferase (ALT) determination and renal
      cortical slices were prepared for p-aminohippuric acid (PAH) incorporation. The
      comparison, between gavage vehicles, of the slopes and ED50 of the dose-response
      curves, although not significantly different, indicated clear trends for enhanced
      potency with CO for CHCl3 nephrotoxicity but not for CCl4 hepatotoxicity.
      However, ALT values, a measure of the severity of effect for CCl4, also indicated
      that CO, when compared to EL620 and Tw-85, tended to enhance CCl4 hepatotoxicity
      at low toxicity incidence. Furthermore, CO clearly enhanced the severity of
      effect for CHCl3 nephrotoxicity, as measured by the slice-to-medium PAH ratios,
      at high dosage. The greater severity of the lesion produced by exposure to these
      chemicals, when administered in CO, is consistent with the trends observed for
      their potency (dose-response curves). Our results agree with an increased
      toxicity of haloalkanes by the gavage vehicle CO reported in the literature.
      Thus, CO should be considered a potential confounder in hepato- and
      nephrotoxicity assays.

PMID- 9233382
TI  - Metabolism and disposition of dimethyl hydrogen phosphite in rats and mice.
AB  - A study of dimethyl hydrogen phosphite (DMHP) by the National Toxicology Program
      (NTP) indicated that chronic administration by oral gavage resulted in an
      increased incidence of neoplastic lesions in the lungs and forestomachs of
      Fischer 344 rats but not in B6C3F1 mice. The current study was designed to
      evaluate the metabolic basis, if any, of this species selectivity by studying the
      metabolism and disposition of [14C]DMHP in the respective strains of rats and
      mice. Results of this study indicate that DMHP administered at a range of dose of
      10-200 mg/kg was readily and near completely absorbed from the gastrointestinal
      tracts of rats and mice. DMHP-derived radioactivity was eliminated primarily as
      CO2 in the expired air, 44-57%, and urine, 28-49%, and very little was collected
      in feces, 1-2%, or as volatile organics, 2-3%. DMHP-derived radioactivity was
      widely distributed in tissues of rats and mice, with the highest concentrations
      observed in the liver, kidneys, spleen, lungs, and forestomach, and the lowest in
      brain, skeletal muscle, and adipose tissue. The disappearance of radioactivity
      from mouse tissues was approximately twice as rapid as from rat tissues. In
      vitro, DMHP was metabolized to formaldehyde by the microsomal fractions of liver,
      lungs, kidneys, forestomach, and glandular stomach. In vivo, DMHP was metabolized
      to the product of demethylation, monomethyl hydrogen phosphite (MMHP), which was
      excreted in urine. Results of this study indicate that the NTP carcinogenicity
      study with DMHP was carried out within the dose range in which the absorption,
      metabolism, and disposition of DMHP are linear in both species. Apparent species
      dependent differences in the metabolism and disposition of DMHP are limited to
      the more rapid metabolism and elimination by the mouse. Therefore, the species
      dependent variations in the carcinogenicity of DMHP are most likely attributable
      to factors other than metabolism and disposition.

PMID- 9233383
TI  - Morphometric changes in the prepubertal female rat thyroid gland following acute
      exposure to 2,2',4,4'-tetrachlorobiphenyl and Aroclor 1242.
AB  - Weanling female Sprague-Dawley rats were given either 2 or 5 consecutive daily
      doses of 30 mg/kg 2,2',4,4'-tetrachlorobiphenyl (CB 47) or a total dose of 120
      mg/kg Aroclor 1242 divided into 2, 3, or 5 daily doses by intraperitoneal
      injection. One day after the final dose, serum total thyroxine (T4) was
      determined and thyroid glands were collected and prepared for morphometric
      analysis. Serum T4 increased between 20 and 25 d of age, but declined to 35-52%
      of controls by d 25 in PCB-treated rats. In rats receiving only 2 doses of CB 47,
      the declines in serum T4 were more modest but the thyroid follicular epithelial
      cell height increased from 9 microns to 10-12 microns and the colloid area
      decreased from 1100 microns2 to 800-900 microns2. In Aroclor 1242-treated rats,
      follicular cell height increases and colloid area decreases were somewhat
      greater; serum T4 was higher (partially restored) in the rats having received
      earlier doses. The rapid response of the thyroid gland to moderate decreases in
      serum T4 attenuates the observed decrease in T4 and may mask effects on T4
      metabolism in short-term structure-activity studies. Morphometric measurements
      may be helpful in characterizing early and/or transient responses to toxicants
      such as PCBs that have multiple endocrine disrupting effects.

PMID- 9233385
TI  - Mouse chromosome 2.

PMID- 9233384
TI  - Mouse chromosome 1.

PMID- 9233386
TI  - Mouse chromosome 3.

PMID- 9233387
TI  - Mouse chromosome 4.

PMID- 9233388
TI  - Mouse chromosome 5.

PMID- 9233389
TI  - Mouse chromosome 6.

PMID- 9233390
TI  - Mouse chromosome 7.

PMID- 9233391
TI  - Mouse chromosome 8.

PMID- 9233392
TI  - Mouse chromosome 9.

PMID- 9233393
TI  - Mouse chromosome 10.

PMID- 9233394
TI  - Chromosome 11.

PMID- 9233395
TI  - Mouse chromosome 12.

PMID- 9233396
TI  - Mouse chromosome 13.

PMID- 9233397
TI  - Mouse chromosome 14.

PMID- 9233398
TI  - Mouse chromosome 15.

PMID- 9233399
TI  - Mouse chromosome 16.

PMID- 9233400
TI  - Mouse chromosome 17.

PMID- 9233401
TI  - Mouse chromosome 18.

PMID- 9233402
TI  - Mouse chromosome 19.

PMID- 9233403
TI  - Mouse X chromosome.

PMID- 9233404
TI  - Mouse Y chromosome.

PMID- 9233405
TI  - Controversies in pallidal surgery.
AB  - Posteroventral pallidotomy (PVP) has gained a worldwide acceptance after its
      reintroduction by Laitinen et al. in 1992 (56) and many studies have since been
      published. A review of the recent literature reveals that there is variation in
      the clinical indications for this procedure, the surgical technique used and the
      assessment of results. There is no uniform practice in the choice of the
      anatomical target point within the globus pallidus, the imaging of the target
      structure, the intraoperative assessment of the physiological target and the mode
      of evaluation of the surgical results. Although some neurosurgeons advocate that
      the lesion should be in the lateral pallidum, the majority insist it should be in
      the medial pallidum. It is shown here that, as long as the lesion is made at the
      posterior and ventral parts of the globus pallidus, it will necessarily include
      aspects of both medial and lateral posteroventral pallidum. There is a common
      agreement on the effectiveness of pallidal surgery on the L-dopa induced
      dyskinesias, but, its long-term effects on tremor, akinesia, freezing of the gait
      and other genuine parkinsonian symptoms need more extensive evaluation. The
      assessment of the outcome of pallidal surgery in terms of the patient's
      disability, quality of life and coping abilities following surgery seems to have
      been neglected.

PMID- 9233406
TI  - Chronic electrostimulation of ventroposterolateral pallidum: follow-up.
AB  - Introduced in 1992, and first published with report of 3 cases in 1994, the
      ventroposterolateral electrostimulation of the pallidum raised exciting
      prospects. The follow-up of this new approach will be presented in 19 cases with
      at least 6 months control, and up to 42 months. The very favorable effects
      observed in the first series could be confirmed and extended to a larger group of
      patients during a longer period.

PMID- 9233407
TI  - Posteroventral pallidotomy in movement disorders.
AB  - Since 1992 there has been renewed interest in pallidotomy now that the
      limitations and adverse effects of long-term dopaminergic therapy have become
      more apparent and more difficult to control in patients with advanced Parkinson's
      disease. The authors describe the effect of pallidotomy in 19 patients, sixteen
      of whom had advanced Parkinson's disease with painful dystonia and/or response
      fluctuations with severe akinesia while in "off" and dyskinesias while in "on".
      One patient had cortico-basal degeneration with rigidity, one patient had
      secondary dystonia and one had dystonic posturing due to Wilson's disease.
      Fifteen patients underwent unilateral pallidotomy, four patients had a staged
      bilateral procedure. Follow-up ranged from 3 to 42 months (mean 18 months). All
      patients with peak-dose dyskinesias and/or dystonia had marked reduction of
      symptoms, including the cases of Wilson's disease and secondary dystonia. The
      akinesia and rigidity scores of Parkinson-patients in "off" were greatly reduced,
      mainly but not only on the contralateral side. Evaluation by the patients showed
      remarkable improvement of symptoms in 79%, leading to substantially improved
      functional abilities in 68%. In this series the decrease in dopamine-response
      fluctuations, dystonia, hypokinesia and rigidity with functional improvement as
      judged by examiners and patients reflect a significant regain of independence.

PMID- 9233408
TI  - Selection criteria for unilateral posteroventral pallidotomy.
AB  - In an attempt to refine the indications for posteroventral pallidotomy (PVP) the
      authors instituted strict selection criteria which are based on the experience
      gained from the first 60 pallidotomy patients treated at their institution. In
      addition to clinical evaluation, all pallidotomy candidates undergo
      neuropsychological testing and 18F-fluoro-deoxyglucose utilization positron
      emission tomography (FDG/PET). The data from which these criteria were developed
      are presented as are early clinical results. The authors demonstrate that these
      criteria enhance the efficacy of the procedure by assuring therapeutic response
      and reducing the incidence of post-operative dementia. Their indications and
      contraindications for pallidotomy are discussed.

PMID- 9233409
TI  - The effects of pallidotomy on Parkinson's disease: study design and assessment
      techniques.
AB  - Lesions of the internal segment of the globus pallidus are increasingly being
      utilized in the surgical treatment of advanced Parkinson's disease, yet studies
      to demonstrate the safety and efficacy of these procedures are only now being
      completed. The importance of procedural variations between centres in the outcome
      of pallidotomy is not yet known. In order to compare accurately results between
      centres, carefully designed, prospective studies are needed. The authors utilized
      blinded, randomly evaluated videotaped examinations of pre- and post-operative
      patients undergoing microelectrode-guided GPi pallidotomy. Their results
      demonstrate significant effects on contralateral akinesia and tremor in the "off"
      state, and striking attenuation of levodopa-induced dyskinesias in the "on"
      state. More modest effects on postural stability and gait disturbance were seen
      only in non-blinded evaluations. This type of study design should enable many of
      the outstanding issues related to pallidotomy indications, procedures and
      outcomes to be addressed.

PMID- 9233410
TI  - Frameless 3D volume registration of MR data sets for stereotactic pallidotomy.
AB  - Frameless 3D volume registration of Magnetic Resonance (MR) and computed (CT)
      data sets has been described by Kummar et al. [11]. Its use in 3D volume
      registration for stereotactic planning in patients undergoing pallidotomy is
      presented. Pre-operative examinations with the stereotactic frame and
      postoperative examinations without the stereotactic frame can be co-registered
      and reviewed for accuracy of planned and lesional coordinates.

PMID- 9233411
TI  - Unilateral pallidotomy for Parkinson's disease promptly improves a wide range of
      voluntary activities--especially gait and trunk movements.
AB  - 26 patients with Parkinson's disease were assessed in the OFF state 2-3 days
      before and one week after pallidotomy for the time to complete each of 25
      standardized motor tasks testing a wide range of voluntary activities important
      for daily living. After pallidotomy there were substantial improvements across
      this wide range of activities. Patients completed tasks that they could not
      perform preoperatively. In general for individual tasks (a) preoperative and
      postoperative scores were directly related, and (b) the absolute improvement
      (preop time-postop time) was directly related to preoperative performance:
      numerical improvements were greater in patients who were worse preoperatively.
      When the 25 tasks were ranked according to improvement relative to preoperative
      performance postoperative improvements were successively greater for (a) limbs
      ipsilateral to pallidotomy, (b) contralateral limbs, and (c) standing and
      walking. The best results were for activities in which the trunk plays a large
      part.

PMID- 9233412
TI  - The side-effects and complications of posteroventral pallidotomy.
AB  - The side-effects and complications of posteroventral pallidotomy are analysed in
      138 consecutive patients who underwent 152 pallidotomies. Transient side-effects,
      lasting less than three months, appeared in 18% of the patients, that is, 16.5%
      of the surgical procedures. Long term complications, lasting more than 6 months,
      were noted in 10% of the patients, that is, 9.2% of the surgical procedures.
      Sixteen complications occurred alone or in various combinations in 14 patients
      and included fatigue and sleepiness (2), worsening of memory (4), depression (1),
      aphonia (1), dysarthria (3), scotoma (1), slight facial and leg paresis (2) and
      delayed stroke (2). Complications such as dysarthria and paresis could be
      attributed to MR- or CT-verified pallidal lesions lying too medially and
      encroaching on the internal capsule. Two of the patients with deterioration in
      memory had some memory impairment before surgery, and the aphonic patient had
      dysphonia preoperatively. The study suggests that stereotactic MRI and careful
      impedance monitoring and macro-stimulation of the posteroventral pallidum area
      should be sufficient for minimizing the risk of complications; the stereotactic
      lesion should be centered within the posterior ventral pallidum without
      involvement of internal capsule. It is concluded that pallidotomy is a safe
      procedure if performed on cognitively alert patients, and it seems that both the
      incidence and especially the severity of complications are lower for
      posteroventral pallidotomy than for thalamotomy.

PMID- 9233413
TI  - Deep brain stimulation and thalamotomy for tremor compared.
AB  - Deep brain stimulation (DBS) and thalamotomy are both capable of abolishing
      tremor. However, no technique is perfect and if thalamotomy proves inadequate so
      that tremor recurs, presumably because of suboptimal lesion location, the only
      option is to repeat the thalamotomy. With DBS all that has been necessary to date
      is to change the parameters of stimulation. Similarly with complications such as
      the "cerebellar" ones and paraesthesiae. If these occur after thalamotomy one can
      only wait and hope that they will subside and they do not always do so. With DBS,
      changing the parameters in the authors' patients has so far been successful in
      eliminating them. DBS, like thalamotomy is very effective for controlling tremor
      in Parkinson's disease (PD) and essential tremor (ET) and for improving dexterity
      in ET, but both techniques are less useful for the control of dopa dyskinesia,
      Parkinsonian rigidity, or impaired dexterity in PD, though DBS may be better than
      thalamotomy for the latter condition. On the other hand, both DBS and thalamotomy
      are very effective in improving dexterity in PD and ET may depend upon the fact
      that in PD bradykinesia is a major component, whereas in ET only the tremor is.
      The advantages of DBS over thalamotomy have to be weighed against the peculiar
      risks of DBS and of course, its cost.

PMID- 9233414
TI  - Treatment of deafferentation pain by chronic stimulation of the motor cortex:
      report of a series of 20 cases.
AB  - Twenty patients with deafferentation pain were treated by chronic stimulation of
      the motor cortex. The central fissure was localized using stereotactic MRI and
      the motor cortex was mapped using intra-operative somatosensory evoked
      potentials. Seven patients with trigeminal neuropathic pain experienced definite
      pain relief varying between 40 and 100%. Ten patients had central pain secondary
      to central nervous system lesions. A satisfactory long-lasting pain control (pain
      relief > 40%) was obtained in five of them (50% of cases). One patient with pain
      from peripheral nerve injury obtained more than 80% pain relief. Two patients had
      pain from spinal cord lesions. One did not respond but the other obtained an
      excellent long-term result. The location of the effective stimulation plots was
      in agreement with the somatotopic maps of the primary motor cortex. One patient
      developed a small extradural haematoma which resolved spontaneously. None of the
      patients developed seizure activity. This study confirms the potential value of
      motor cortex stimulation in the treatment of certain forms of intractable pain,
      especially in cases with trigeminal neuropathic pain.

PMID- 9233415
TI  - Obsessive compulsive disorder and the right hemisphere: topographic analysis of
      lesions after anterior capsulotomy performed with thermocoagulation.
AB  - Considerable but uncontrolled evidence suggests that stereotactic capsulotomy by
      means of thermolesions may provide symptomatic relief for patients with otherwise
      therapy refractory "malignant" obsessive compulsive disorder (OCD). Unlike in
      other functional stereotactic interventions, target localization for capsulotomy
      is based upon anatomical definition only. Few systematic attempts have been made
      to correlate the site and size of the capsular lesions with postoperative
      clinical outcome. Between 1976 and 1989 bilateral thermo-capsulotomy (TC) was
      performed in 22 OCD patients. In 19 patients complete quantitative pre- and
      postoperative psychiatric rating of OCD symptoms and long-term postoperative MRI
      studies were available. Cohorts of patients fulfilling criteria for good or poor
      outcome were contrasted, cases with intermediate treatment effect being excluded.
      Median postoperative MRI follow-up was 8.4 years (2.4-20.3 y). 9/19 patients
      fulfilled criteria for good postoperative outcome. In these patients all lesion
      sites overlapped covering a small area within the right anterior limb of the
      internal capsule. Lesions within the group of patients with poor outcome (n = 5)
      were located elsewhere, mostly further anterior in the internal capsule.
      Differences of lesion overlap between the two outcome groups were significant for
      the right side (Fisher's Exact Test: p < 0.005). Common topographic features of
      lesion sites within the right internal capsule were identified in OCD patients
      responding favourably to capsulotomy.

PMID- 9233416
TI  - Lesionectomy in epileptogenic temporal lobe lesions: preoperative seizure course
      and postoperative outcome.
AB  - A series of 54 patients operated on for temporal epileptogenic lesions is
      reported: 36 had slow growing tumours, 18 supratentorial cavernous angiomas. The
      patients were divided into two different groups according to the presence of
      seizures controlled (group 1) or not controlled (group 2) by antiepileptic drugs
      (AEDs). All the patients underwent preoperative scalp EEG and magnetic resonance
      imaging (MRI). They were operated on by pure lesionectomy, associated with
      amygdalo-hippocampectomy in 8 cases of uncontrolled seizures. Postoperatively
      they underwent MRI examination which revealed an incomplete lesionectomy in 12
      cases. Patients were followed up after surgery for at least 2 years, 6 of them
      were reoperated on for the persistence (or regrowth) of the tumour. The results
      of epilepsy outcome are reported. These cases underline the importance of
      preoperative electroclinical study, in order to determine the relationship
      between lesion location and epileptic focus. If good concordance is present, a
      complete lesionectomy is enough to cure the patient. In other cases associated
      amygdalo-hippocampectomy leads to better results, while more complicated cases
      may need preoperative stereo-EEG studies.

PMID- 9233417
TI  - Low grade glioma in intractable epilepsy: lesionectomy versus epilepsy surgery.
AB  - In approximately 30% of patients with intractable partial epilepsy, an intra
      axial cerebral lesion is the aetiology of the seizure disorder. Lesions adjacent
      to mesiotemporal structures often result in secondary epileptogenicity in the
      same region. The authors present 22 cases of low-grade gliomas associated with
      intractable epilepsy. In 15 cases the location was temporal (8 extra-hippocampal
      and 7 with invasion of the amygdalo-hippocampus), 7 cases were extratemporal in
      eloquent areas. The eight extra-hippocampal tumours were originally treated with
      lesionectomy. The seizure outcome was class 1 in only 4 cases, the remaining 4
      were class 4 according to Engel's classification. The 4 cases with class 4
      outcome required additional temporal lobectomy associated with amygdalo
      hippocampectomy for seizure control. The 2 cases with associated hippocampal
      atrophy at MRI after lobectomy had outcome class 1. The 2 cases without
      hippocampal atrophy at MRI presented outcome class 2. The 7 cases with invasion
      of amygdala and hippocampus were treated with selective lesionectomy+amygdalo
      hippocampectomy. In all these cases convergence of focal structural abnormality,
      ictal onset of epileptiform EEG abnormality and interictal epileptiform EEG
      abnormality provided powerful evidence of focal epileptogenicity. All these
      patients had a favourable epilepsy outcome (class 1-2). In the seven
      extratemporal cases the first step was lesionectomy. In 1 case located in the
      parietal region intraoperative mapping was required. 5 had class 1 outcome, one
      case had outcome class 2 and one case had an outcome class 4. The last patient
      required a second step operation with intraoperative strip and deep electrode
      monitoring that led subsequently to a frontal lobectomy. This patient is seizure
      free 2 years after surgery. There was no perioperative mortality and post
      operative morbidity was 3/22. This study indicates that lesionectomy may be the
      first step procedure if the structural abnormality is localized to extra-temporal
      eloquent cortex and concordance is documented. Patients may subsequently be
      candidates for a cortical resection as a second step procedure if the
      lesionectomy does not provide an adequate reduction in seizure tendency. Since
      MRI identified hippocampal atrophy was predictive in this study of an
      unsatisfactory seizure outcome after lesionectomy, MRI defined dual pathologies
      consisting of a temporal lesion plus hippocampal atrophy necessitate temporal
      lobectomy+amygdalo-hippocampectomy. In patients with negative MRI findings of
      hippocampal atrophy and temporal lobe lesions, intraoperative
      electrocorticography and deep electrode monitoring are indicated for planning the
      surgical strategy.

PMID- 9233418
TI  - Incorporation of ultrasonic imaging in an optically coupled frameless
      stereotactic system.
AB  - Frameless stereotactic interactive tracking systems relate a point in the
      surgical field to a corresponding point on the patients MR or CT scans in
      multiple planes. A basic weakness with these systems is that they cannot
      compensate for movement of target points due to brain shift caused by CSF
      drainage or lesion removal. Real time images can be obtained using ultrasonic
      techniques but the poor quality and definition and the ill-defined scan plane
      make interpretation difficult and reduce the usefulness of this modality. The
      authors have combined these two modalities by mounting light emitting diodes
      (LEDs) on the ultrasonic probe, thus allowing a "virtual tip" to be developed in
      the centre of the ultrasonic beam, and tracked via an optically coupled frameless
      stereotactic system (Radionics, OTS). This has allowed a direct correlation
      between pre-operative MR and the per-operative ultrasonic images using
      reformatted MR images. Ultrasound images are obtained through a separate skull
      opening and the image plane is determined by the position of the virtual tip. The
      ultrasonic and MR images are presented side by side for visual comparison.
      Minimally invasive tumour resection or haematoma removal could be carried out
      under ultrasonic guidance with direct interactive relation to the preoperative MR
      scans. Alternatively interactive image directed surgical procedures can be up
      dated in real time by dynamic ultrasonic images taken in clearly defined scan
      planes.

PMID- 9233419
TI  - Magnetoencephalography (MEG) in epilepsy surgery.
AB  - Whole-scalp MEG has proved to be a suitable tool for preoperative evaluation of
      patients suffering from drug-resistant focal epilepsy. MEG recordings are non
      invasive and safe for the subject, and no demanding preparations of the patient
      are needed before measurement. The MEG recordings may reveal several epileptic
      foci, and the order of activation can be resolved in millisecond scale. In
      addition, epileptic cortex can be localized with respect to important functional
      areas, such as sensorimotor or visual cortices, and these areas can be visualized
      in a same brain reconstruction. This helps in patient selection and planning of
      the operation. Moreover, prior MEG localization of epileptic foci and
      functionally important areas aids in placing the intracranial electrodes to right
      places, when needed.

PMID- 9233420
TI  - Integration of functional brain mapping in image-guided neurosurgery.
AB  - Magnetoencephalographic (MEG) brain mapping was performed in 90 patients with
      lesions associated with eloquent sensorimotor cortex. The MEG-derived
      sensorimotor mapping information was utilised for risk analysis and planning.
      Subsequently, these patients underwent either stereotactic volumetric resection,
      stereotactic biopsy or non-surgical management of their lesions. In seventeen
      patients, the MEG sensorimotor localization was integrated into an operative
      stereotactic database (consisting of CT, MRI and digital angiography) to be used
      in an interactive fashion during computer-assisted stereotactic volumetric
      resection procedures. The spatial relationship between the MEG derived functional
      anatomy, the structural/radiological anatomy and the pathology could then be
      viewed simultaneously, thereby affording a safer trajectory and approach. In
      addition, the real-time availability of functional mapping information in an
      interactive fashion helped reduce surgical risk and minimise functional
      morbidity. All of these patients had resection of their lesions with no change in
      their neurological status. In conclusion, MEG is a non-invasive, accurate, and
      reproducible method for pre-operative assessment of patients with lesions
      associated with eloquent sensory and motor cortex. The interactive use of MEG
      functional mapping in the operating room can allow for a safer approach and
      resection of these eloquent cortex lesions.

PMID- 9233421
TI  - Significant reduction of seizure incidence and increase of benzodiazepine
      receptor density after interstitial radiosurgery in low-grade gliomas.
AB  - Epilepsy is the leading symptom in low grade gliomas. In order to evaluate the
      effect of interstitial radiosurgery on seizure incidence the authors
      retrospectively analysed the outcome of 80 patients with temporal grade-II
      astrocytomas and a history of epilepsy. Patients were treated by 125-iodine
      temporary implants using 60 Gy as reference dose. The dose rate was 9.6 +/- 1.6
      cGy/h. Median follow-up was 4.1 years. In 20 patients benzodiazepine receptor
      imaging was performed using single photon emission computed tomography and
      iomazenil. Treatment with carbamazepine alone led to a significant reduction in
      seizure incidence with 28% of patients being seizure-free (p < 0.05).
      Interstitial radiosurgery led to a further reduction of seizures rendering 40% of
      patients seizure-free after 3 months. After 6 months only 21% of patients still
      had seizures that were refractory to medical treatment (p < 0.01). SPECT imaging
      revealed that all tumours had a significant reduction of benzodiazepine receptors
      which also applied to the surrounding brain. After interstitial radiosurgery of
      tumours, receptor density increased in brain adjacent to the tumour (0.68 to 0.94
      ratio ipsi to contralateral brain, p < 0.01) coincident with significant tumour
      shrinkage. Thus, in epileptogenic temporal low grade gliomas, interstitial
      radiosurgery not only reduced the tumour burden but also effectively treated the
      concomitant epilepsy, resulting in 79% of patients being seizure-free after
      combined treatment by radiosurgery and anticonvulsive medication. These results
      compare favourably to the outcome after resection in lesional epilepsy raising
      the issue of radiosurgery as a less invasive alternative to open epilepsy
      surgery.

PMID- 9233422
TI  - Functional neurosurgery aided by use of an electronic brain atlas.
AB  - The authors present their experience in the use of an atlas-based computer system
      for preoperative functional neurosurgery planning and postoperative analysis. It
      has also some potential for intraoperative support. The system is based on a
      deformable electronic version of "Atlas of Stereotaxy of the Human Brain" by
      Schaltenbrand and Wahren. This atlas is used for interactive segmentation and
      labelling of clinical data in two- and three dimensions, and for definition of
      stereotactic targets. The Schaltenbrand-Wahren atlas microseries are digitized,
      enhanced, segmented, labelled, aligned and organized into atlas volumes. They are
      mutually preregistered, and three-dimensional models of the structures are
      constructed. The atlas may be interactively registered with an actual patient's
      data. A computer system is developed which provides data interpolation,
      reformatting, registration, visualization, navigation, mensuration and path
      display and editing in two- and three dimensions. The system increases the
      accuracy of target definition, reduces the time of planning and the time of the
      procedure itself. It also constitutes a research platform for the construction of
      more advanced neurosurgery supporting tools and brain atlases.

PMID- 9233423
TI  - Gene transfer of suicide genes for the treatment of malignant gliomas: efficacy,
      limitations, and perspectives for a combined immunotherapy.
AB  - The potential of gene therapy strategies for malignant gliomas that are based on
      retroviral-mediated transfer of a "suicide gene" such as Herpes Simplex Virus
      thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for
      example), has been emphasized by the promising results obtained by several
      groups. However, further experimental data as well as preliminary clinical
      results indicate that the low efficiency of retroviral-mediated gene transfer in
      vivo as well as difficulties for the diffusion of the prodrug inside the tumour
      mass can limit the efficacy of this form of gene therapy. To achieve a more
      effective limitation of tumour growth other approaches may be combined with the
      "suicide gene" strategy and the enhancement of the immunological response to the
      tumour by cytokine gene transfer is prominent among these approaches. The
      authors' experiments in nude mice confirm the antineoplastic role of IL-4 and
      encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk
      genes in immunocompetent animals.

PMID- 9233424
TI  - Anti-angiogenic gene therapy of malignant glioma.
AB  - Glioblastoma, one of the best vascularized tumours in humans, appears well suited
      for an antiangiogenic therapy. VEGF (vascular endothelial growth factor), the
      most important angiogenesis factor identified to date, is highly expressed in
      glioblastoma. VEGF is particulary upregulated in palisading cells adjacent to
      necroses and has subsequently been shown to be hypoxia-inducible in glioma cells
      in vitro. VEGF-receptor tyrosine kinases, VEGF-R1 (flt-1) and VEGF-R2 (flk-1),
      are induced in a tumour stage dependent manner during glioma progression and are
      exclusively expressed in tumour vascular endothelial cells. These observations
      suggest that VEGF-receptors are promising targets for tumour endothelial cell
      specific therapy. The ability to block VEGF-signalling by the VEGF-R2 dominant
      negative mutant identifies the VEGF/VEGF-R2 system as a major regulator of glioma
      angiogenesis. Several experimental approaches demonstrate that in rat gliomas
      tumour growth can be prevented by the inhibition of angiogenesis. These findings
      are of pivotal importance for the development of anti-angiogenic therapies in
      glioblastoma patients.

PMID- 9233426
TI  - Risk analysis of LINAC radiosurgery in patients with arteriovenous malformation
      (AVM).
AB  - The purposes of this analysis were the evaluation of the toxicity of stereotactic
      single dose irradiation in patients with an arteriovenous malformation (AVM) and
      the comparison of the authors' own results with already existing risk prediction
      models. Computed-tomography (CT) or magnetic-resonance (MR) images, and clinical
      data of patients treated with linear accelerator radiosurgery for an AVM were
      analysed retrospectively. Using the Cox proportional hazards model (1), the
      relevance of treatment parameters and dose-volume relationships to the occurrence
      of radiation-induced tissue changes (oedema and localised blood-brain-barrier
      breakdown) were assessed. The 81 patients selected for analysis had a mean follow
      up of 28.9 months (range: 9.0-65.7 months). Radiation-induced tissue changes (22
      out of 81 i.e. 27.2%) were documented on CT or MR images 6.3-33.8 months after
      radiosurgery (median time: 12.8 months). The actuarial risk at 2 years was 32.1%
      for the development of neuroradiological changes and 20.1% for the development of
      symptomatic tissue alteration. The coefficient of total volume receiving a
      minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox
      proportional hazards model. These results demonstrate the particular
      vulnerability of normal brain tissue to single dose irradiation. Optimal
      conformation of the therapeutic isodose line to the 3D configuration of the
      target volume may help to reduce side effects.

PMID- 9233425
TI  - Gene therapy in brain tumours: implications of the size of glioblastoma on its
      curability.
AB  - The authors have used the thymidine kinase/ganciclovir system to block
      glioblastoma multiforme neoplastic cells in vivo, both in experimental animals
      and in two patients in which the more conventional therapies had been
      unsuccessful. In the Wistar rat it was found that the curability potential of the
      system is correlated with tumoral volume. Tumours smaller than 20 mm3 can be
      cured with defective retrovirus that do not carry the Herpes simplex thymidine
      kinase (Hsvtk) gene. While tumours smaller than 150 mm3 can regress totally by
      the kinase/ganciclovir system, those above that size cannot be cured by this
      treatment. In humans the situation seems very similar in that the authors have
      been unable either to reduce the tumour size of recurrent patients with tumour
      volumes larger than 100 cm2 applying the standard thymidine kinase/ganciclovir
      gene therapy or to prolong their survival time more than 8 months [7]. When a
      combination of size reduction by neurosurgery and gene therapy was used the
      survival time increased considerably. Two patients have been treated by partial
      surgery and repeated treatment with thymidine kinase/ganciclovir through an
      Ommaya reservoir connected to a catheter leading into the tumour cavity. The
      magnetic resonance imaging (MRI) of these patients show only a residual tumoral
      growth along side the tumoral bed. The procedure may be partially controlling the
      proliferation of cancerous cells, because, these two patients having recurrent
      glioblastoma, are alive 11 and 17 months after the beginning of the treatment.

PMID- 9233427
TI  - Effect of LINAC radiosurgery on regional cerebral blood flow, glucose metabolism
      and sodium-potassium AtPase in skull base meningiomas and metastasis.
AB  - Stereotactic radiosurgery is an elegant alternative to microsurgery in both skull
      base meningiomas and solitary brain metastasis. Though efficacy for both entities
      has been established prognostic variables pertaining to individual tumour biology
      have not yet been identified. Therefore the authors measured regional glucose
      utilisation, thallium-uptake and blood flow in 20 patients (10 meningiomas, 10
      metastasis) before and after LINAC radiosurgery. Measurements were performed
      using SPECT and stable xenon-CT. The mean tumour dose given was 16.3 and 19.5 Gy
      in meningiomas and metastasis respectively. Metastatic tumours were
      hypermetabolic in comparison to contralateral normal brain and responders to
      radiosurgery showed a lower tumour/brain ratio than non-responders (1.43 vs 0.91
      respectively, p < 0.01). Meningiomas did not exhibit hypermetabolism and
      therapeutic outcome was not related to glucose utilisation. Thallium-uptake,
      however, was closely related to therapeutic response in meningiomas (1.37 vs 2.2
      in responders vs non-responders, p < 0.01). This relationship could not be
      established in metastatic lesions. Blood flow was widely distributed in both
      meningiomas and metastasis (26-72.8 and 30.2-70.8 ml/100 g/min). rCBF did not
      correlate with therapeutic outcome. Using FDG-SPECT and thallium-201-SPECT the
      authors were able to distinguish between tumours likely to respond to
      stereotactic radiosurgery and those not prone to respond. Furthermore the
      methodology can be used to monitor therapeutic response in treated tumours before
      morphologic changes occur.

PMID- 9233428
TI  - Potential role of in vitro 1H magnetic resonance spectroscopy in the definition
      of malignancy grading of human neuroepithelial brain tumours.
AB  - The increasing sensitivity of neuro-imaging in the diagnosis of brain expanding
      lesions is not directly related to biopathological specificity and new
      technological approaches are under study. In particular Magnetic Resonance
      Spectroscopy (MRS) allows evaluation of some biochemical pathways whose metabolic
      alterations may be correlated with the nature and malignancy grading of primary
      brain tumours. In the present study the author performed an in vitro high field
      1H MRS (9.4 and 14.1 T) analysis of specimens obtained from stereotactic biopsy
      or microsurgical removal of primary brain tumours. Different samples derived from
      heterogeneous areas and/or infiltrated perilesional regions were examined. This
      study was principally focused on malignancy grading of gliomas and its
      correlation with the ratio (R) between the resonance band arising from choline
      containing compounds (between 3.14 and 3.35 ppm) and the total creatine signal
      (3.0 ppm). Analyses allowed significant discrimination between astrocytomas (R =
      2.4 +/- 0.6) and glioblastoma (GBM) (R = 4.4 +/- 1.3) [p < 0.002]; however the
      results did not allow discrimination between differentiated and anaplastic
      astrocytomas. The GBM showed the largest spread of values corresponding to their
      higher level of tissue heterogeneity and de-differentiation. Studies on non
      astrocytic brain tumours indicated that even higher R values were exhibited by
      oligodendrogliomas, even in well differentiated forms (p < 0.02 with respect to
      GBM). Moreover, preliminary observations indicated that signals arising from
      other metabolites may also contribute to a differential diagnosis of different
      oncotypes. Among these glycine appears particularly relevant, since higher levels
      were measured for this amino acid in GBM with respect to both astrocytomas and
      oligodendrogliomas.

PMID- 9233429
TI  - Stereotactic brain biopsy guided by positron emission tomography (PET) with [F
      18]fluorodeoxyglucose and [C-11]methionine.
AB  - The aim of the present study was to compare the contribution of the labelled
      tracers [C-11]methionine (Met) and [F-18]-fluorodeoxyglucose (FDG) in positron
      emission tomography (PET)-guided stereotactic biopsy of non resectable brain
      lesions. Twenty-five patients underwent combined Met-PET-, FDG-PET- and
      computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic
      biopsy according to a previously described technique for stereotactic FDG-PET.
      Met-PET and FDG-PET images were analyzed to determine which tracer offers the
      best information to guide at least one stereotactic biopsy trajectory.
      Histological diagnosis was obtained in all patients (23 tumours and 2 non
      tumorous lesions). All tumours had an area of abnormal Met uptake and were
      biopsied under PET-guidance. FDG uptake in the tumour was higher than in the grey
      matter and was used for target selection in 12 of 23 tumours. Eleven of them were
      located in the basal ganglia or the brainstem. Met was used for target selection
      in 11 of 23 tumours where there was no FDG uptake or where FDG uptake was
      equivalent to that of the grey matter. Ten of them were located in the cortex.
      Two nontumoral lesions had no Met uptake and were biopsied under CT- or MR
      guidance only. Forty-three out of 53 stereotactic trajectories obtained in these
      25 patients were based on PET-defined targets and had an area of abnormal Met
      uptake. These trajectories always yielded a diagnosis of tumour. Moreover, all
      tumorous trajectories had an area of abnormal Met uptake. Finally, all non
      diagnostic trajectories (n = 4) were CT/MR-defined because there was no area of
      abnormal Met uptake. These results suggest that patients who can benefit the most
      from Met-PET guidance could be selected pre-operatively. In conclusion, this work
      shows that Met is a good alternative to FDG for target selection in PET-guided
      stereotactic brain biopsy.

PMID- 9233430
TI  - Glioma cells transduced with selection transgenes may not form gliomas in vivo
      and can also inhibit glioma formation by admixed wild glioma cell lines.
AB  - Following in vitro lipofection transfection of the rat glioma cell line A15A5
      with the plasmid transgene CMV/HyTK, which confirms hygromycin resistance and
      ganciclovir sensitivity, a series of experiments was planned in which the
      "bystander" phenomenon would be evaluated using the rodent implantation glioma
      model. However examination of the brain of rodents in which the A15A5HyTK cells
      were implanted showed no evidence of glioma growth. Furthermore, rodents having
      intracerebral implantation of (i) wild A15A5 and A15A5HyTK cells in a 50/50 mix,
      (ii) wild A15A5 and A15A5HyTK cells in a 90/10 mixture and (iii) wild C6 and
      A15A5HyTK cells in a 50/50 mix all failed to grow macroscopic tumours by 15-17
      days irrespective of whether the animals had been administered ganciclovir (GCV)
      in the week before sacrifice. Neuropathological and immunocytochemical analysis
      of the implantation sites showed no difference between the GCV and saline treated
      groups of animals for any implantation cell mix. These observations confirm
      previous results that suggest transduction of malignant rodent glioma cell lines
      with a variety of selection, oncogenic and marker genes significantly impairs
      their in vivo tumorigenic potential compared to the wild type cell lines. This
      study also demonstrates that even without GCV treatment the transduced cells
      inhibit, by an unknown mechanism(s), the tumorigenicity of other non transfected
      malignant cells. The implications of this study for gene therapy of human
      malignant glioma are discussed.

PMID- 9233431
TI  - The molecular biology of coronaviruses.

PMID- 9233432
TI  - The Tetraviridae.

PMID- 9233434
TI  - New aspects in the pathogenesis of polyomavirus-induced disease.

PMID- 9233433
TI  - Role of host proteins in gene expression of nonsegmented negative strand RNA
      viruses.

PMID- 9233435
TI  - Viral pathogens of the penaeid shrimp.

PMID- 9233436
TI  - Nucleopolyhedrovirus interactions with their insect hosts.
AB  - It is clear from this brief review that our understanding of the molecular cross
      talk between insects and their baculovirus pathogens is still very limited.
      Studies in cell culture have taught us a great deal about the basic baculovirus
      molecular machinery and how it is regulated, and in many cases this information
      has been predictive of what occurs in infected insects. Frequently, however,
      studies in cell culture do not adequately predict the infection process in insect
      hosts, as demonstrated by viral mutants (some of which were discussed in this
      review) that behave identically to wild-type virus in cell culture but differ
      markedly in larvae. More baculovirus studies, therefore, need to be conducted in
      vivo if we are to improve our understanding of the complex interactions between
      baculoviruses and their hosts. Conducting baculovirus studies in insects (or at
      least in primary cell culture) also offers the opportunity to address questions
      that reach beyond the baculovirus community in significance. For example, almost
      all of our knowledge of viral fusion mechanisms comes from infection of cells in
      culture where the pH is neutral or acidic and the temperature is constant at 27
      degrees or 37 degrees C. An answer to the question of how the ODV envelope fuses
      with the microvillar membrane of columnar epithelial cells in the highly alkaline
      midgut environment at low temperatures will not only be important for an improved
      understanding of baculovirus infection in the natural world, but will also
      constitute a new chapter on viral entry mechanisms. Similarly, the answer to the
      question of how baculovirus nucleocapsids move basally within microvilli promises
      to involve factors and/or a mechanism not yet described by cell biologists, and
      so will constitute a valuable contribution to both baculovirology and cell
      biology. There are many more such examples of biological mechanisms that can be
      uniquely explored within the context of baculoviruses and their insect hosts,
      some of which have been highlighted in this review. As more and more young
      investigators realize the importance of combining a knowledge of virology,
      molecular technology, and insect biology, however, many of the outstanding
      mysteries will be solved.

PMID- 9233437
TI  - Replicase-mediated resistance to plant virus disease.

PMID- 9233438
TI  - The role of the physician in geriatric medicine in the ageing society.
      Introduction.

PMID- 9233439
TI  - In the past. The role of the physician in geriatric medicine in the ageing
      society.

PMID- 9233440
TI  - The role of the physician in geriatric medicine in the ageing society. In
      epidemiology.

PMID- 9233441
TI  - The role of the physician in geriatric medicine in the ageing society. In the
      community.

PMID- 9233442
TI  - The role of the physician in geriatric medicine in the ageing society. Screening
      in the community.

PMID- 9233443
TI  - The role of the physician in geriatric medicine in the ageing society. 1. In
      acute medicine: the integrated model.

PMID- 9233444
TI  - The role of the physician in geriatric medicine in the ageing society. 2. In
      acute medicine: the age-defined model.

PMID- 9233445
TI  - The role of the physician in geriatric medicine in the ageing society. 3. In
      acute medicine: the traditional model.

PMID- 9233447
TI  - The role of the physician in geriatric medicine in the ageing society. In
      collaboration with orthopaedic surgeons.

PMID- 9233446
TI  - The role of the physician in geriatric medicine in the ageing society. In
      rehabilitation.

PMID- 9233448
TI  - The role of the physician in geriatric medicine in the ageing society. In
      collaboration with old age psychiatrists.

PMID- 9233449
TI  - The role of the physician in geriatric medicine in the ageing society. In
      continuing care.

PMID- 9233450
TI  - The role of the physician in geriatric medicine in the ageing society. In
      management.

PMID- 9233451
TI  - The role of the physician in geriatric medicine in the ageing society. In
      training.

PMID- 9233452
TI  - The role of the physician in geriatric medicine in the ageing society. In the
      future.

PMID- 9233453
TI  - T-cell repertoire and HIV infection: facts and perspectives.

PMID- 9233454
TI  - Biological correlates of HIV-1 heterosexual transmission.
AB  - OBJECTIVES: To study the role of HIV-1 biological phenotype, viral load and
      neutralizing antibodies in male-to-female heterosexual transmission of HIV-1.
      METHODS: Seven transmitting and seven non-transmitting HIV-1-seropositive
      heterosexual male index cases were included in the present study. All couples had
      engaged in unprotected sex for a period of over 1 year. Transmission was defined
      by the seroconversion of the female sexual partner. Virus isolates were tested in
      MT-2 cells for replication and syncytia induction. HIV-1 RNA plasma load was
      measured by the branched DNA technique. Serum neutralizing activity to primary
      HIV-1 isolates was tested by using peripheral blood mononuclear cells (PBMC) as
      target cells. RESULTS: Non-transmitting index cases had a lower HIV-1 RNA
      concentration in plasma than transmitting index cases. Non-transmitting index
      cases also tended to have serum neutralizing activity with broad specificity and
      to have viruses with low replicative capacity, as characterized by 50% infectious
      dose titres in PBMC and by the lack of MT-2 tropism. CONCLUSIONS: The results
      indicate that plasma viral-RNA load is a marker for transmission. Moreover, an
      interplay between the host immune response and viral replication may modulate the
      level of viral load and thereby influence HIV-1 transmission.

PMID- 9233455
TI  - Oral transmission of Candida albicans between partners in HIV-infected couples
      could contribute to dissemination of fluconazole-resistant isolates.
AB  - BACKGROUND: Fluconazole resistance has emerged among Candida albicans isolates
      and has been associated with the prolonged or repeated use of the drug. This
      study was designed to discover whether transmission of oral isolates could occur
      between sexual partners and thereby explain fluconazole resistance in patients
      never treated with the drug. MATERIALS AND METHODS: The oral flora of 10 HIV
      infected couples (five heterosexual and five homosexual) were studied. In vitro
      susceptibility testing and genotyping (restriction fragment length polymorphism
      with EcoRI and HinfI) were used to delineate strain relatedness for 230 clones
      (five clones per sample, one to four samples per patient). RESULTS: The genetic
      diversity of the clones with one DNA subtype was specific to a given patient or a
      given couple, except in one case in which unrelated patients shared clones of the
      same genotype. The persistence of clones between partners was stable over time in
      six out of 10 couples and only transient in one couple. Fluconazole resistance in
      isolates from patients who had never been treated with azoles was associated in
      three patients with the first episode of oropharyngeal candidiasis and treatment
      failure. CONCLUSION: The observation that couples tended to share genetically
      indistinguishable clones was highly suggestive of transmission between partners.
      This phenomenon may, in part, explain the pathogenesis of oropharyngeal
      candidiasis and the increased frequency of fluconazole resistance both in vitro
      and in vivo.

PMID- 9233456
TI  - Asymptomatic HIV infection is characterized by rapid turnover of HIV RNA in
      plasma and lymph nodes but not of latently infected lymph-node CD4+ T cells.
AB  - OBJECTIVES: To study the kinetics of plasma viraemia and HIV-infected lymph-node
      cells in stable asymptomatic HIV infection with high CD4+ T-cell counts. METHODS:
      Nine asymptomatic HIV-infected patients with stable CD4+ T-cell counts (510-1350
      x 10(6)/l) were treated with a triple-drug combination. Plasma viraemia was
      determined at days 0, 3, 7, 10, 14, 21 and 28 of treatment [Roche polymerase
      chain reaction (PCR) and ultrasensitive PCR assay]. Sequential lymph-node
      biopsies were examined in four patients before and after 4 weeks of treatment.
      Productively infected cells were counted in lymph-node sections (in situ
      hybridization). The infection rates of FACS-sorted CD4+ lymph-node T cells and
      the expression of single-spliced, double-spliced and full-length HIV transcripts
      were determined. RESULTS: HIV plasma RNA half-lives ranged from 1.4 to 2.7 days.
      Viral turnover varied between 0.07 and 7.54 x 10(8) copies per day. The number of
      productively infected lymph-node cells as well as the amount of extracellular
      virus in germinal centres was markedly reduced during treatment, paralleled by a
      clearance of single-spliced, double-spliced and full-length HIV transcripts from
      CD4+ lymph-node T cells. Plasma viraemia remained detectable with an
      ultrasensitive PCR assay in three out of four patients. The percentage of lymph
      node CD4+ T cells harbouring proviral DNA decreased only slightly. CONCLUSIONS:
      The kinetics of HIV replication are rapid in stable asymptomatic infection, and
      the magnitude of replication varies considerably. Productively infected lymph
      node cells and extracellular virus in germinal centres undergo a rapid turnover,
      whereas latently infected CD4+ T cells have a lower rate of turnover. The latter
      may contribute substantially to viral persistence during therapy.

PMID- 9233457
TI  - Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1
      infection using cytoplasmic cytokine detection on single cell level by flow
      cytometry.
AB  - OBJECTIVE: To characterize changes of Th1/Th2 cytokine production by peripheral
      blood mononuclear cells (PBMC) that occur during the course of HIV infection by
      cytoplasmic cytokine staining on single cell level. DESIGN AND METHODS: Mitogen
      stimulated PBMC from 16 healthy donors, 18 HIV-1-infected individuals without
      AIDS and 14 patients with AIDS were stained intracellularly with fluorescein
      labelled MAb against interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-gamma.
      Additionally, co-staining of CD4+ T-cell, CD8+ T-cell, natural killer (NK) cell,
      B-cell and monocytic markers was performed. Fluorescence staining was analysed by
      three-colour flow-cytometry. RESULTS: A reduced percentage of IL-2 and IFN-gamma
      (Th1 type)-producing cells among CD4+ T cells from HIV-1-infected individuals
      could be demonstrated. There was a continuous decrease of IFN-gamma-producing
      CD4+ T cells in the course of HIV infection and a dramatic reduction of IL-2
      expressing cells among CD4+ T cells in patients with AIDS. In contrast to Th1
      cytokines, the frequency of Th2 cytokine expressing cells among CD4+ T cells
      increased in HIV-infected individuals. The maximum frequency of IL-4-expressing
      cells among CD4+ T cells was seen in HIV-infected individuals without AIDS,
      whereas the rate of IL-10-producing cells was highest in patients with AIDS. In
      HIV-infected individuals no significant proportion of Th0 cells expressing both
      Th1 and Th2 cytokines was detectable. In CD8+ T cells the percentage of IL-2 was
      expressing cells decreased continuously accompanied by a strong increase of the
      frequency of IFN-gamma-producing cells. CONCLUSION: The decreased percentage of
      cells expressing IL-2 and IFN-gamma in conjunction with an increased proportion
      of IL-4- and IL-10-producing cells among the CD4+ T cells in HIV-1-infected
      individuals demonstrate a Th1 to Th2 cytokine shift in the course of HIV
      infection on a single cell level. There was no evidence of a Th1 to Th0 cytokine
      shift. In addition to the loss of CD4+ T cells in HIV infection, the qualitative
      changes of Th1/Th2 cytokine expression may serve as a marker for progressive
      failure of cell-mediated immunity.

PMID- 9233459
TI  - Survival after a very low (< 5 x 10(6)/l) CD4+ T-cell count in individuals
      infected with HIV.
AB  - OBJECTIVE: To describe survival after a CD4+ T-cell count of less than 5 x
      10(6)/l and to identify possible baseline factors associated with outcome.
      DESIGN: A prospective cohort study. SETTING: A large teaching hospital in North
      London. PATIENTS AND PARTICIPANTS: Patients treated at the Royal Free Hospital,
      London, who had at least one reported CD4+ T-cell count of less than 5 x 10(6)/l
      and were being followed up for clinical care prior to the date of this cell
      count. MAIN OUTCOME MEASURE: Death. METHODS: Proportional hazards models, Kaplan
      Meier analysis. RESULTS: One-hundred and sixty-nine patients were included in the
      study. The median survival after a very low CD4+ T-cell count was 0.95 years (95%
      confidence interval, 0.78-1.19), although 20% survived for over 2 years. Older
      age and a previous AIDS diagnosis were related to poorer outcome. A higher CD8+ T
      cell count at baseline was also associated with a better prognosis. CONCLUSIONS:
      A CD4+ T-cell count of less than 5 x 10(6)/l did not necessarily mean imminent
      death, with a median survival after this count of just under 1 year. These
      results will enable clinicians to provide appropriate counselling for patients at
      this late stage and to plan terminal care.

PMID- 9233458
TI  - Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8 encephalitis in
      HIV-positive and -negative individuals.
AB  - OBJECTIVE: Kaposi's sarcoma-associated herpesvirus (KSHV) human herpesvirus type
      8 (HHV-8) has been associated with Kaposi's sarcoma and a variety of benign
      lymphoid proliferations including angioimmunoblastic lymphadenitis with
      dysproteinemia and Castleman's disease. KSHV/HHV-8 has also been associated with
      inflammatory conditions including interstitial pneumonitis. Although
      herpesviruses are commonly associated with encephalitis in immunosuppressed
      individuals, KSHV/HHV-8 has not previously been associated with central nervous
      system disease other than lymphoma. The first cases of KSHV/HHV-8 associated
      encephalitis have been described. METHODS AND DESIGN: KSVH/HHV-8 sequences were
      evaluated in brain biopsies from three cases of otherwise unexplained
      encephalitis from three patients, two of whom were positive for HIV.
      Amplification of the polymerase chain reaction product was confirmed with
      Southern blot hybridization on three separate occasions, and with appropriate
      positive and negative controls. RESULTS: All three cases of encephalitis were
      associated with KSHV/HHV-8 sequences. Characteristic lesions included endothelial
      cell swelling and perivascular cuffing by lymphocytes. CONCLUSIONS: KSHV/HHV-8
      was associated with encephalitis in immunosuppressed individuals, and should have
      been considered in the differential diagnosis of unexplained viral encephalitis.
      KSHV/HHV-8 may have tropism for the central nervous system.

PMID- 9233460
TI  - Altered concentrations of appetite regulators may contribute to the development
      and maintenance of HIV-associated wasting.
AB  - OBJECTIVE: To examine the relation of circulating appetite neuropeptides, CCK-8
      sulphate (CCK-8s) and beta-endorphin, and the tumour necrosis factor-alpha (TNF
      alpha) and soluble TNF receptors (sTNFR) to the anorexia and wasting associated
      with HIV-infection. DESIGN: Cross-sectional analysis. SETTING: A university-based
      HIV/AIDS ambulatory clinic in Madrid, Spain. PARTICIPANTS: Thirty-six randomly
      selected AIDS patients without concomitant diseases or secondary infections were
      classified into two groups: 19 patients with wasting and 17 with normal body
      weight, and 18 healthy controls. MEASUREMENTS: Nutritional status was evaluated
      by anthropometry, laboratory parameters and self-report of appetite. Plasma
      levels of TNF-alpha and sTNFR proteins p55 (sTNFR-p55) and p75 (sTNFR-p75) were
      determined by enzyme immunoassay, whereas CCK-8s and beta-endorphin levels were
      measured by radioimmunoassay. RESULTS: AIDS patients with wasting had
      significantly higher plasma concentrations of CCK-8s, but lower levels of beta
      endorphin when compared to well-nourished AIDS patients (P < 0.01) or controls (P
      < 0.001). Mean levels of TNF-alpha, and sTNFR-p55 and sTNFR-p75 were greater in
      AIDS patients with wasting than in asymptomatic AIDS patients or in controls. No
      significant association was observed between any of these circulating peptides
      and the parameters of malnutrition. CONCLUSIONS: An activation of the TNF system,
      together with reciprocal changes in plasma concentrations of two neuropeptides
      with opposing appetite regulation, that is increased concentrations of CCK-8s but
      lower levels of beta-endorphin, are associated with the presence of HIV wasting.
      We hypothesize that these changes may contribute to the development of HIV
      wasting by producing a pathological inhibition of appetite.

PMID- 9233461
TI  - Receptive and expressive language function of children with symptomatic HIV
      infection and relationship with disease parameters: a longitudinal 24-month
      follow-up study.
AB  - OBJECTIVES: To longitudinally assess the receptive and expressive language
      functioning of children with symptomatic HIV disease and to explore the
      relationship between immune status, computed tomography (CT) brain scan
      abnormalities, and language dysfunction over time. METHODS: Children with
      symptomatic HIV infection were administered an age-appropriate standardized
      comprehensive language test and general cognitive measure prior to starting
      antiretroviral therapy (n = 44) and again after 6 months (n = 29) and 24 months
      (n = 17). CD4 percentage and CT brain scans were also obtained at each
      evaluation. RESULTS: Expressive language was significantly more impaired than
      receptive language at the baseline, 6- and 24-month evaluations. No significant
      changes over time were found in receptive or expressive language from baseline to
      after 6 months of antiretroviral therapy, but despite treatment, language scores
      declined significantly between 6 and 24 months. Overall cognitive function,
      however, remained stable from baseline to 24 months. Age-adjusted CD4 percentage
      increased significantly over the initial 6 months, then remained stable. Overall
      CT brain scan severity ratings did not change significantly over 24 months.
      CONCLUSION: Expressive language was consistently more impaired than receptive
      language over 24 months, further supporting an earlier finding that expressive
      language was differentially affected by HIV in children with symptomatic disease.
      Both receptive and expressive language declined significantly after 24 months
      despite antiretroviral therapy, although overall cognitive function remained
      stable. Thus, functioning in some domains may be more vulnerable to the effects
      of HIV and global measures of cognitive ability may mask such differential
      changes in specific brain functions.

PMID- 9233462
TI  - HIV-associated brain pathology in the United Kingdom: an epidemiological study.
AB  - OBJECTIVES: To examine the epidemiology of HIV-associated neuropathology in the
      United Kingdom and to investigate whether the prevalence of different forms of
      HIV-associated brain pathology varies with exposure category. DESIGN: The study
      was a cross-sectional survey; data was analysed from the Medical Research Council
      National AIDS Neuropathology database. SETTING: Information was gathered from
      throughout England, Scotland and Wales. SUBJECTS: Individuals who died from AIDS
      in the United Kingdom and had a postmortem examination. The database comprised 7%
      of all AIDS deaths in the United Kingdom between 1982 and 1993. MAIN OUTCOME:
      Neuropathological diagnoses based on internationally accepted neuropathological
      terminology of AIDS-related brain lesions. RESULTS: HIV encephalitis was the most
      prevalent pathological diagnosis, occurring in 25.3% [95% confidence interval
      (CI), 21.0-29.6] of the study sample. Statistically significant independent
      associations for the occurrence of HIV encephalitis were found for injecting drug
      use (odds ratio, 6.86; 95% CI, 2.91-16.17), and age less than 30 years at death
      (odds ratio, 3.58; 95% CI, 1.99-6.44). Vascular lesions were significantly higher
      among blood product recipients, 95% of whom were haemophiliacs. CONCLUSIONS: This
      was the first epidemiological investigation of HIV-associated brain pathology in
      the United Kingdom. HIV encephalitis appeared to occur more frequently in
      injecting drug users and those who died younger. Whereas the findings must be
      interpreted cautiously, one hypothesis was that differences in the route of
      transmission may have affected the manifestation of HIV-associated brain damage.

PMID- 9233463
TI  - Impact of HIV infection on the development, clinical presentation, and outcome of
      tuberculosis among children in Abidjan, Cote d'Ivoire.
AB  - OBJECTIVE: To assess the impact of HIV infection upon the development, clinical
      presentation, and outcome of tuberculosis (TB) among children. DESIGN: Case
      control study and prospective cohort study. METHODS: From March 1994 to November
      1995, children aged 0-9 years with newly diagnosed TB were enrolled at the two
      outpatient TB centers and the two principal university hospitals in Abidjan, Cote
      d'Ivoire. Children were examined, blood samples were collected for HIV serology
      and lymphocyte phenotyping, chest radiography was performed, and gastric
      aspirates and sputum samples were collected for acid-fast bacilli smear and
      culture. Children were then followed every 2 months during a standard 6-month
      course of anti-TB therapy. To examine risk factors for TB, age- and sex-matched
      healthy control children were enrolled from among the siblings of children
      referred for TB skin testing. RESULTS: Overall, 161 children with TB were
      enrolled, including 39 (24%) with culture-confirmed pulmonary TB, 80 (50%) with
      clinically diagnosed pulmonary TB, and 42 (26%) with extrapulmonary TB. Children
      with TB were significantly more likely than 161 control children to be HIV
      seropositive (19 versus 0%), to have a past TB contact (55 versus 16%) and to
      live in very low socioeconomic status housing (24 versus 6%). No significant
      differences between HIV-seropositive and seronegative children were found in the
      distribution of radiologic abnormalities for pulmonary TB or in the site of
      extrapulmonary TB. The mortality rate in HIV-seropositive children was
      significantly higher than in seronegative children (23 versus 4%; relative risk,
      3.6; 95% confidence interval, 2.0-6.6), and all deaths in HIV-seropositive
      children with available lymphocyte subtyping results occurred in those with a CD4
      percentage of < 10%. CONCLUSIONS: This study documents the importance of HIV
      infection as an independent risk factor for the development of TB in children,
      and demonstrates that HIV-related immunosuppression is a critical risk factor for
      mortality in this population.

PMID- 9233465
TI  - Disseminated Mycobacterium avium complex disease in the Swiss HIV Cohort Study:
      increasing incidence, unchanged prognosis.
AB  - OBJECTIVES: Disseminated disease due to Mycobacterium avium complex (MAC)
      bacteria is thought to occur less frequently in Europe than in the USA. This
      study investigated time trends in the occurrence of, and survival with,
      disseminated MAC disease in the Swiss HIV Cohort Study (SHCS). DESIGN, SETTING
      AND PARTICIPANTS: The SHCS participants who were free of disseminated MAC disease
      at registration were stratified by calendar period (1987-1989, 1990-1992, 1993
      1995) in which the first recorded CD4 count was 0-49, 50-99, or 100-199 x
      10(6)/l. Kaplan-Meier estimates of the probability of developing and surviving
      disseminated MAC disease were calculated for these nine independent groups.
      Multivariate analyses were performed using Cox proportional hazards regression.
      RESULTS: The analysis was based on 6052 participants enrolled between January
      1987 and December 1995 and 202 incident episodes of disseminated MAC disease
      recorded during a mean follow-up time of 3.5 years. The cumulative probability of
      MAC disease at 2 years in individuals with CD4 counts of 0-49 x 10(6)/l in 1987
      1989 was 9.8% [95% confidence interval (CI) 4.4-15.2%], increasing to 29.8% (95%
      CI, 20.8-38.8%) in 1993-1995. Amongst those with CD4 counts from 50-99 x 10(6)/l
      these probabilities were 11.9% (95% CI, 5.9-17.8%), and 21.6% (95% CI, 13.9
      29.2%), respectively. After adjusting for CD4 count the relative hazard of
      developing disseminated MAC disease in 1993-1995, compared with 1987-1989, was
      1.37 (95% CI, 0.92-2.04). Median survival following diagnosis was 7.9 months with
      no improvement over time. CONCLUSIONS: The incidence of disseminated MAC disease
      among SHCS participants has increased over time. More profound levels of
      immunosuppression amongst recent study entrants were found to explain this. When
      compared with US cohorts studied over the same calendar period the incidence of
      disseminated MAC disease in the SHCS appears to be lower. These findings are
      consistent with a secular effect of a more mature HIV epidemic in the US but
      direct comparison between the SHCS and a similar prospective cohort in the US
      should be undertaken to clarify this issue.

PMID- 9233464
TI  - The impact of illness disclosure and custody plans on adolescents whose parents
      live with AIDS.
AB  - OBJECTIVES: To describe the disclosure and custody planning of parents living
      with AIDS and the impact of these on their adolescents' adjustment. METHODS: An
      examination of the association of multiple behaviour problems in children and the
      illness disclosure and custody plans of their parents living with AIDS. RESULTS:
      Both mothers (87%) and fathers were significantly more likely to disclose their
      HIV serostatus to adolescents (73%), compared with younger children (23%); only
      44% disclosed their illness to all their children; 11% disclosed to none. Most
      parents (80%) living with AIDS had discussed their custody plans. However, only
      30% initiated legal plans, typically for younger children. Adolescents who were
      informed of their parents' serostatus engaged in more sexual risk acts, smoked
      more cigarettes, and reported more severe substance use and greater emotional
      distress than uninformed adolescents. Legal custody arrangements were not
      associated with adolescent adjustment at recruitment or follow-up. CONCLUSIONS: A
      longitudinal analysis of the impact on adolescents of the behaviours of parents
      living with AIDS is needed.

PMID- 9233466
TI  - Sexual risk of HIV infection among expatriates posted in AIDS endemic areas.
AB  - OBJECTIVE: To assess the prevalence of HIV infection and related risk factors
      among Dutch expatriates returning from assignment in sub-Saharan Africa, Latin
      America, and South and South-east Asia. METHODS: From July 1994 to January 1996,
      a questionnaire on the risks of sexual exposure was completed by 864 respondents,
      and blood samples were taken. RESULTS: Of the 634 men, 41% reported having sex
      with casual or steady local partners and 11% with casual or steady expatriate
      partners, during an average stay of 26 months in the previous 3 years. Of the 230
      women, these figures were 31 and 24%, respectively. Of the men with local casual
      partners (29%), 59% paid for sex at least once. For men as well as women, having
      sexual contacts abroad was associated with younger age, positive intention prior
      to departure to have sex abroad, being single at departure, and, only for the
      men, working for a commercial organization, and feelings of loneliness and
      boredom. Among men, consistent condom use with casual local partners was 69%, and
      with casual expatriate partners 63%. Among women, these figures were 64 and 48%,
      respectively. Consistent condom use with steady local or expatriate partners was
      much lower. Among men, non-consistent condom use with casual partners was more
      prevalent if they had been abroad for a longer time, condoms were not taken along
      from The Netherlands, the country where they were posted was Asian, and the
      estimated HIV prevalence among the local population was lower. Among the women,
      non-consistent condom use was more prevalent if condoms were not taken along, and
      if they did not have the intention before departure to have sex abroad. Of the
      persons from whom blood could be obtained, one man was HIV-positive. Another man
      who refused to participate in the study indicated that he was HIV-positive.
      CONCLUSIONS: Although 23% of the expatriates had unprotected sex with partners
      from endemic areas, very few HIV infections were found. In comparison with a
      previous study among this population carried out in 1987-1989, which found five
      out of 1968 expatriates to be HIV-infected, consistent condom use with casual
      local partners did increase considerably (from 21 to 67%). However, health
      education is needed to reduce the risk of HIV infection, which should emphasize
      the sociocultural differences in sexual practices.

PMID- 9233467
TI  - Timing of mother-to-child HIV-1 transmission and diagnosis of infection based on
      polymerase chain reaction in the neonatal period by a non-parametric method.

PMID- 9233468
TI  - Increase in the frequency of mutation at codon 215 associated with zidovudine
      resistance in HIV-1-infected antiviral-naive patients from 1989 to 1996.

PMID- 9233469
TI  - Bacillary angiomatosis: a role for Phyllobacterium?

PMID- 9233470
TI  - Azithromycin for relapsing cerebral toxoplasmosis in AIDS.

PMID- 9233471
TI  - Confusing criteria for the diagnosis of toxoplasmic encephalitis in AIDS.

PMID- 9233472
TI  - Clinical application of recombinant human erythropoietin in anemic HIV patients.

PMID- 9233473
TI  - Infant-maternal HIV-specific immunoglobulin G1 antibody ratios as an indicator of
      vertical transmission.

PMID- 9233474
TI  - HIV-1 RNA is not detectable in the cerebrospinal fluid during antiretroviral
      combination therapy.

PMID- 9233475
TI  - Clinical significance of qualitative human cytomegalovirus (HCMV) detection in
      cell-free serum samples in HIV-infected patients at risk for HCMV disease.

PMID- 9233476
TI  - Identification of Mhc-Mamu-DQB1 allele combinations associated with rapid disease
      progression in rhesus macaques infected with simian immunodeficiency virus.

PMID- 9233477
TI  - Chemokine receptors and HIV-2.

PMID- 9233478
TI  - Functional hearing results in revision stapes surgery.
AB  - OBJECTIVE: The object of our study was to review the results of 63 revision
      stapes surgeries performed from 1978 to 1994. RESULTS: The most common cause of
      failure was the displacement of the prosthesis, followed by ossicular chain
      problems and oval window fibrosis. Postoperative hearing improvement within a 20
      dB air-bone gap was achieved in 58.7% of the patients. Hearing gain was closely
      linked to the operative findings. Better results occurred when prosthesis
      problems were found. Evaluation of the hearing results by using Glasgow benefit
      plot gave evidence of symmetric normal hearing in only 40% of the cases.
      CONCLUSIONS: Prevention of the cause of failure during the primary stapes
      surgeries, lessening the surgical trauma, seems to provide the most favorable
      hearing results.

PMID- 9233479
TI  - Development of a new outcomes instrument for conductive hearing loss.
AB  - OBJECTIVE: The objective was to design and validate a disease-specific outcomes
      instrument for use in conductive hearing loss (CHL). STUDY DESIGN: The study was
      a retrospective survey of 47 patients recently treated for CHL with either a
      hearing aid or surgery. Patients were tested with the newly designed instrument
      (the Hearing Satisfaction Scale [HSS]), previously validated hearing-specific
      instruments, and a generic quality-of-life instrument. SETTING: The study was
      performed in an academic tertiary referral center. MAIN OUTCOME MEASURES: These
      included test-retest reliability, internal consistency reliability, content
      validity, criterion validity, and construct validity of the HSS. RESULTS: Test
      retest reliability (r = 0.72, p < 0.001) and internal consistency reliability
      were adequate (Cronbach's alpha was 0.83 and 0.74 for the two subscales of the
      HSS). Criterion validity for individual items was adequate (r = 0.45, p = 0.02)
      using audiometric data as the criterion standard. Construct validity was also
      high using results from other instruments; both convergent and divergent validity
      of the HSS was demonstrated. In addition, the HSS demonstrated the ability to
      differentially discriminate between subgroups when grouped by level of hearing
      loss. CONCLUSIONS: The HSS is a valid and reliable instrument for use in outcomes
      research on conductive hearing loss.

PMID- 9233480
TI  - Evaluation of quality of life and symptoms after translabyrinthine acoustic
      neuroma surgery.
AB  - OBJECTIVE: This study aimed to describe the consequences of acoustic neuroma
      surgery in terms of symptoms and quality of life. STUDY DESIGN: This study was a
      retrospective case review. SETTING: The surgery was conducted in Uppsala, Sweden.
      PATIENTS: A consecutive sample of acoustic neuroma patients operated on between
      1988 and 1994. INTERVENTION: All patients had been operated on with the
      translabyrinthine technique. MAIN OUTCOME MEASURES: A questionnaire was
      constructed including questions about the surgery and symptoms. The House and
      Brackmann scale was used for grading facial function and the Brackmann and Bars
      scale was used for self-assessment of facial function. RESULTS: Follow-up data
      were collected by a postal questionnaire sent out and returned by 141 patients,
      which yielded a 90% response rate. Normal to moderately impaired facial function
      (House I-III) was evident in 85.2% of patients, although residual facial problems
      were reported. Most considered hearing to be worse after surgery (80%), and
      tinnitus was found in 60% of the sample. Balance problems (45%), dizziness (19%),
      and headache/pain (22%) were also reported. Work ability was affected in 23%, and
      37% reported a continued need for medical consultations, mainly because of facial
      problems and pain. Most (89%) were pleased with the preoperative information.
      CONCLUSIONS: This study showed that few patients with acoustic neuroma had
      experienced negative social consequences after surgery. Although not linked to
      the operation, residual symptoms were reported that may necessitate further
      rehabilitation.

PMID- 9233481
TI  - Acoustic neuroma surgery: outcome analysis of patient-perceived disability.
AB  - OBJECTIVE: Numerous studies have investigated the outcome of acoustic neuroma
      (AN) treatment using classical medical measures. In an effort to describe the
      long-term lifestyle consequences of AN removal from the patient's perspective,
      patients filled out detailed questionnaires concerning their functional status.
      STUDY DESIGN: This was a retrospective survey. SETTING: This study was performed
      at a tertiary referral center. PATIENTS: A total of 130 late postoperative
      acoustic neuroma patients were surveyed a minimum of 6 months following surgery
      (average, 39 months). Survey response rate was 65% (130/200). MAIN OUTCOME
      MEASURES: The main outcome measures were the patient's perception of their
      hearing, balance, facial expression, and eye function in relation to its impact
      upon the activities of daily life. A comparison of pretreatment with long-term
      posttreatment functional levels. RESULTS: When asked to designate their "most
      significant" symptom, hearing loss was by far most prevalent (61.3%), followed by
      balance troubles (14.3%) and facial weakness (10.1%). The relatively low
      incidence of facial weakness as the patient's dominant complaint was somewhat
      surprising. When considering the incidence of each symptom, women were more
      likely to complain of facial weakness, dry eye, and headache, whereas men had a
      marginally higher incidence of hearing loss and imbalance. Patient age had no
      apparent influence upon either the distribution or severity of symptomatic
      complaints. Both hearing in the tumor ear and overall auditory function (e.g.,
      the ability to understand in a restaurant) tended to worsen following surgery.
      One finding, which was both unanticipated and intriguing, was the improvement in
      sound localization ability reported by 57% of patients following surgery.
      Although the proportion of patients complaining of frequent tinnitus increased
      postoperatively, the number of patients who found the tinnitus troublesome
      decreased markedly. In terms of balance function, only 31% preoperatively and 15%
      postoperatively described themselves as free of balance difficulties. An aid to
      ambulation (e.g., cane, walker) was needed in five patients (4%) preoperatively,
      two of whom regained the ability to walk independently following tumor removal.
      CONCLUSIONS: These functional outcome data provide much useful information to
      both patient and clinician to consider when contemplating the optimal course of
      AN management. Although virtually all acoustic neuroma patients have some degree
      of persistent symptoms over the long-term, the data indicates that most of these
      are attributable to the tumor itself as opposed to the after effects of its
      surgical removal. The relatively slight differences between preoperative and late
      postoperative symptom profiles was a rather unanticipated finding. As the degree
      of disability tends to increase with larger tumor sizes, these data tend to
      support a policy of early intervention.

PMID- 9233482
TI  - Socioeconomic impact of acoustic neuroma surgery.
AB  - OBJECTIVE: This study aimed to assess the impact of acoustic neuroma (AN) surgery
      on socioeconomic function. STUDY DESIGN: This study was a retrospective postal
      survey. SETTING: The study was performed at a tertiary referral center. PATIENTS:
      One hundred thirty late postoperative AN patients were surveyed a minimum of 6
      months after surgery (average 39 months). The survey response rate was 65% (130
      of 200). MAIN OUTCOME MEASURES: These included effect of AN surgery on
      employability, income, activities of daily living, social involvement, and
      psychological well-being. RESULTS: When comparing preoperative occupational
      status with latest follow-up, 2 of 125 (1.6%) became unemployed from their usual
      occupations. An additional 15 of 125 (12%) retired, attributing their retirement
      to the effects of the tumor itself (3), an aftermath of surgery (2), and causes
      unrelated to their AN (10). After AN removal, two formerly unemployed patients
      became employed. Among those remaining employed, there was no significant impact
      of surgery on either income or work responsibility. Return to normal activity was
      gradual: < or = 6 weeks, 31%; < or = 3 month, 64%; and < or = 6 months, 84%.
      Among activities of daily living, the tasks most often impaired (both before and
      after tumor removal) were ladder climbing and night driving, whereas dressing and
      bathing were seldom problematic. Overall, patients reported a minor decline in
      ability to perform routine daily activities after tumor removal. Social function
      (contact with friends, community involvement, and participation in sports)
      changed little after surgery. The incidence of both stress and depression
      decreased slightly after tumor removal. CONCLUSIONS: The economic, social, and
      psychological impact of AN and its surgical management appears to be relatively
      minor, with few individuals having life altering consequences.

PMID- 9233484
TI  - Mitochondrial DNA deletions associated with aging and possibly presbycusis: a
      human archival temporal bone study.
AB  - HYPOTHESIS: We attempted to determine if the common mitochondrial DNA aging
      deletion is also associated with presbycusis. BACKGROUND: Presbycusis is the most
      common cause of deafness in adults in the United States, affecting approximately
      40% of the population older than 75 years of age. The ability to identify a
      gene(s) or a specific genetic deficit(s) associated with presbycusis has
      significant clinical importance. METHODS: The current study examined
      mitochondrial DNA (mtDNA) from cochlear sections of 34 human temporal bones: 17
      with normal hearing and 17 with presbycusis. DNA was extracted from celloidin
      embedded temporal bone sections; and specific oligonucleotide primers were
      designed to amplify the cytochrome b gene and a 4,977 base pair (bp) deletion of
      the mtDNA. Polymerase chain reaction (PCR) was used to amplify the base pair
      products that correspond to targeted gene regions, and sequencing was used to
      verify the products. RESULTS: Fourteen of the 17 patients with hearing loss
      showed the 4,977 bp deletion and this deletion was present in only eight of the
      17 human specimens with normal audiograms. The cytochrome b gene was amplified
      from all specimens. CONCLUSIONS: The current study demonstrates the presence of a
      4,977 bp deletion in human mitochondrial DNA genome that is associated with aging
      and with some forms of presbycusis. These results, coupled with previous animal
      studies, suggest that this 4,977 deletion may be associated with presbycusis.

PMID- 9233483
TI  - Comparison of long-term hearing results after vestibular neurectomy,
      endolymphatic mastoid shunt, and medical therapy.
AB  - OBJECTIVE: This study aimed to compare the hearing changes in the long term after
      vestibular neurectomy, endolymphatic mastoid shunt, and medical treatment in
      classic Meniere's disease. STUDY DESIGN: A retrospective case review was
      conducted based on audiologic follow-up between 5 and 21 years. SETTING: The
      study was performed at two centers in Bari University Hospital, one performing
      vestibular neurectomy as the first surgical procedure for Meinere's disease and
      the other, endolymphatic mastoid shunt. PATIENTS AND INTERVENTIONS: Of 68
      patients with intractable idiopathic Meniere's disease, 29 underwent middle fossa
      vestibular neurectomy, and 17 had endolymphatic mastoid shunt; 22 were offered
      surgery but declined. MAIN OUTCOME MEASURES: Outcome measures were puretone
      average (PTA), speech reception threshold, and speech discrimination score before
      and after treatment. RESULTS: PTA declined by an average of 9.3 dB in neurectomy
      patients, 13.3 dB in patients undergoing endolymphatic mastoid shunt, and 18.1 dB
      in patients who were offered surgery but declined. Patients were subdivided into
      two cohorts based on their preoperative or initial PTA. In the patients who had
      PTA scores worse than 50 dB initially, the PTA declined an average of 4.3 dB in
      the vestibular neurectomy group, 11.5 dB in the endolymphatic sac group, and 4 dB
      in the nonsurgical group. In the patients with PTA > or = 50 dB initially, the
      PTA declined an average of of 25.3 dB in the vestibular neurectomy group, 16.1 in
      the endolymphatic sac group, and 26.2 dB in the nonsurgical group. Although shunt
      patients with good hearing initially deteriorated less than neurectomy patients
      and less than patients who declined surgery, the difference was not significant.
      CONCLUSIONS: These results indicate that patients with poor hearing stabilized,
      while patients with good hearing continued to deteriorate. The same conditions
      were observed in the patients who had surgery and those who were offered surgery
      but declined.

PMID- 9233485
TI  - Distortion product otoacoustic emissions: hit and false-positive rates in normal
      hearing and hearing-impaired subjects.
AB  - OBJECTIVE: This study aimed to establish hit and false-positive rates for
      distortion product otoacoustic emissions (DPOAEs) using a commercial instrument.
      STUDY DESIGN: This was a prospective study. The examiners performing the DPOAEs
      were blinded to pure-tone audiometric results. A decision matrix analysis was
      used to determine hit and false-positive rates for absolute amplitude, three
      amplitude-to-noise ratios, and three conditions that combined these two
      parameters. SETTING: The study was performed at a tertiary care, outpatient
      clinical laboratory facility. PATIENTS: Subjects with normal hearing and those
      with sensorineural hearing loss participated in the study. MAIN OUTCOME MEASURES:
      Main outcome measures were hit and false-positive rates for various DPOAE
      measures. RESULTS: Hit and false-positive rates were better for high than low
      frequencies. As absolute amplitude and amplitude-to-noise ratios increased hit
      and false-positive rates improved. Optimal hit rates generally exceeded 80%;
      false-positive rates were approximately 20% in the high-frequency range. Although
      the absolute amplitude measures seemed more useful than various ratio measures,
      there were advantages to using both parameters clinically. CONCLUSIONS: DPOAEs
      have acceptable hit and false-positive rates for high frequencies but not for
      lower frequencies. DPOAE amplitude-to-noise ratios of +3 and even +6 dB may not
      be clinically feasible based on the current data. The overall findings obtained
      on the commercial instrument in this study compare favorably with previous
      studies of a similar nature.

PMID- 9233486
TI  - Results of speech processor upgrade in a population of Veterans Affairs cochlear
      implant recipients.
AB  - OBJECTIVE: This study aimed to evaluate the change in performance when the Speak
      processing strategy replaced the Mpeak strategy. SUBJECTS: Twenty-one veterans
      who participated in the original Department of Veterans Affairs Multicenter
      Cochlear Implant Study, received the Nucleus F0F1F2 processor (Cochlear Corp.,
      Englewood, CO, U.S.A.) (WSP) and were subsequently upgraded to the Mpeak (MSP)
      processing strategy. METHODS: Closed- and open-set speech recognition in quiet
      and in noise in auditory only conditions at the phoneme, word, and sentence
      levels were evaluated. RESULTS: Changes in audiologic parameters were evaluated
      using a paired t-test for related samples. Statistically significant improvements
      in mean scores were found for all tests and were greatest for the speech-in-noise
      conditions. An examination of individual data revealed that 61% of the subjects
      improved for tests administered in quiet, whereas up to 69% of the subjects had
      improved performance in noise. Subjects with no open set speech discrimination
      using the Mpeak strategy showed no improvement with the Speak strategy.
      CONCLUSIONS: Cochlear implants can provide improved performance using
      modifications to external speech processor hardware and software without changing
      the internal implant.

PMID- 9233487
TI  - Perioperative electrical auditory brain stem response in candidates for pediatric
      cochlear implantation.
AB  - OBJECTIVE: The aim was to investigate the feasibility of recording the electrical
      auditory brain stem response (EABR) evoked by electrical stimulation at the
      promontory (Prom-EABR) as a tool to assist selection of the ear for cochlear
      implantation in young children. STUDY DESIGN: The study group consisted of young
      children for whom the decision to proceed with implantation with the Nucleus mini
      22-channel cochlear implant (Cochlear (UK) Ltd., London, UK) had already been
      made. SETTING: The Prom-EABR was recorded after the children had been
      anesthetised, but before the start of surgery. PATIENTS: A group of 25 children
      (11 boys and 14 girls), whose age at implantation ranged from 2 years 11 months
      to 6 years 8 months (mean age, 4 years 5 months), were investigated.
      INTERVENTION: Recordings of the Prom-EABR were used to determine which ear would
      receive the cochlear implant, providing there were no preexisting
      contraindications regarding selection of the ear. MAIN OUTCOME MEASURE: It has
      been suggested from earlier studies that the characteristics of the amplitude
      input/output (I/O) function of the EABR are related to neuronal survival. If the
      ear with the "better" I/O function is chosen for implantation, it might be
      expected that these children will perform better on average than those in whom
      the ear has been selected at random. RESULTS: Reliable recordings of the Prom
      EABR were achieved in 40 ears (80%) of the 50 ears in the study. In 20 of the 25
      children the technique was actively employed for selection of the ear for
      implantation. CONCLUSIONS: Recording of the Prom-EABR in the operating theater is
      a viable technique. Future analysis of long-term outcome measures of performance
      with the implant will confirm or dispute the benefit of ear selection using the
      Prom-EABR.

PMID- 9233488
TI  - Cause and repair of flap necrosis over cochlear implant.
AB  - OBJECTIVE: The aim of this report was to study the cause and treatment of flap
      related complications over cochlear implant. SETTING: The study was performed in
      an academic tertiary referral center. PATIENT: A 53-year-old Japanese male
      patient had had two retro-auricular skin incisions for tympanomastoidectomy in
      the postauricular region before implantation of a cochlear implant. He also had
      worn a helmet daily during work in his factory. INTERVENTIONS: Corrective surgery
      was performed for reformation of the local blood supply to the overlying skin
      flap and reinforcement of the tissue overlying the implant by use of a superiorly
      based temporal muscle and fascia flap that were sutured with an inferiorly based
      muscle and fascia flap. RESULTS: We successfully transposed the flap covering the
      implant without explantation of the implant. CONCLUSIONS: The delayed development
      of flap necrosis was thought to be due to pressure necrosis produced by the band
      in the patient's helmet lying on the skin over the implant and to poor local
      blood supply in the postauricular area stemming from the two previous skin
      incisions for mastoid surgery performed for cholesteatoma. In those patients who
      wear helmets, it is important to position the cochlear implant sufficiently
      behind the ear and to avoid the use of a helmet.

PMID- 9233489
TI  - Vestibular nerve pathology in cases of intractable vertigo: an
      electronmicroscopic study.
AB  - OBJECTIVE: This study aimed to determine the absence or presence and the nature
      of pathology of the vestibular nerve in case of intractable vertigo. STUDY
      DESIGN: This was a prospective study. SETTING: The study was performed at a
      private practice tertiary referral center. PATIENTS: There-were 42 patients with
      intractable vertigo in the study. INTERVENTIONS: All patients received thorough
      diagnostic examinations and surgical excision of the vestibular nerves. MAIN
      OUTCOME MEASURES: Segments of the superior and inferior vestibular nerves were
      surgically removed, preserved in glutaraldehyde, examined by electronmicroscopy,
      and the findings were correlated with the clinical diagnosis. RESULTS: A variety
      of different types of pathologic lesions were identified, including axon and
      supporting cell degeneration, herpes zoster virus, other viruses, results of
      bacterial infection, and regrowth of nerve after surgical resection. CONCLUSION:
      The vestibular nerves were found to be histologically normal in lesions primarily
      involving the end organ such as most early Meniere's disease cases, benign
      paroxysmal postural vertigo (BPPV), and mild labyrinthine concussion. Vestibular
      nerve degeneration was seen with advanced Meniere's disease, severe labyrinthine
      concussion, and with vascular loops in the internal auditory canal. Herpes zoster
      involves Scarpa ganglion in herpes zoster oticus. Viruses were found in the
      nuclei of vestibular nerve cells in a patient with delayed hydrops. Regrowth of
      the vestibular nerve after surgical resection was confirmed in three cases.

PMID- 9233491
TI  - Prognostic significance of intraoperative facial nerve stimulus thresholds.
AB  - OBJECTIVE: Intraoperative facial nerve monitoring has reduced the incidence of
      facial nerve paralysis associated with acoustic neuroma surgery, but poor facial
      nerve outcomes continue to occur. Intraoperative prediction of facial nerve
      outcome would be advantageous in patient management and counseling. This study
      seeks to evaluate intraoperative facial nerve stimulus thresholds as a tool for
      predicting postoperative facial nerve outcome. STUDY DESIGN: This study is a
      prospective clinical study of the prognostic value of intraoperative stimulus
      thresholds. SETTING: The study was performed at a tertiary referral center.
      PATIENTS: There were 109 patients undergoing excision of acoustic neuromas
      included in this study. INTERVENTIONS: The minimum current required to stimulate
      the facial nerve at the brain stem was prospectively recorded after excision of
      the acoustic neuroma. MAIN OUTCOME MEASURES: Facial nerve outcome was evaluated
      by the House-Brackmann grade. RESULTS: A statistically significant relationship
      was found between poor initial facial nerve outcome and higher stimulus
      thresholds. Long-term impaired facial function was also more common in the higher
      stimulus group compared to that of the lower stimulus groups. CONCLUSIONS:
      Although these findings suggest that intraoperative stimulus thresholds have
      prognostic potential, other prognostic factors should also be considered and
      additional research is needed.

PMID- 9233490
TI  - Evaluating 3D semicircular canal function by perception of rotation.
AB  - OBJECTIVE: We aimed to develop a clinical test of 3D canal dysfunction by
      perceptual matching of motion stimuli as an alternative to vestibular ocular
      reflex assessment. STUDY DESIGN: The study was a comparison with age-matched
      controls. SETTING: The study was performed in a clinical neurophysiology
      laboratory. PATIENTS: Ten patients with acute unilateral vestibular nerve section
      and 9 patients in the chronic stage of recovery, 2 acute-stage and 2 chronic
      stage patients with posterior canal plugging, and 35 healthy individuals were
      studied. INTERVENTIONS: Seated on a motorized rotating chair in darkness,
      subjects were exposed to discrete, raised cosine velocity (60 degrees/s peak)
      rotations, for random displacements < or = 180 degrees rightward and leftward.
      They responded by rotating themselves back to the starting position with a
      joystick control. Horizontal canals were tested with head upright, ipsilateral
      versus contralateral vertical canal pairs were tested with the head down, face
      horizontal and co-planar anterior-posterior canal pairs were tested with the head
      down and turned approximately 45 degrees to the left or right. MAIN OUTCOME
      MEASURES: These were accuracy and symmetry of responses. RESULTS: Normal
      responses were approximately accurate returns to start. Nine patients with acute
      nerve section were hypometric (undershooting start) when displaced toward the
      lesion but normometric to the intact side. Eight chronic-stage nerve section
      patients with chronic dysfunction were hypometric to the lesion for vertical
      canal stimuli, but one third showed normal responses for horizontal canal
      testing. Patients with posterior canal plugging were hypometric specifically
      toward the plugged canal. CONCLUSIONS: The method reliably identifies acute and
      chronic dysfunction of vertical canals and acute dysfunction of horizontal
      canals. Dysfunction of a single canal can be specified.

PMID- 9233492
TI  - Ganglionic hamartoma of the intracanalicular acoustic nerve causing sensorineural
      hearing loss.
AB  - OBJECTIVE: This article highlights the clinical presentation and treatment issues
      of ganglionic hamartoma of the internal auditory canal and emphasizes the
      similarity of this lesion to acoustic neuroma regarding its audiologic and
      radiographic characteristics. STUDY DESIGN: This article is composed of case
      reports and a literature review. SETTING: The study was performed at a university
      hospital/tertiary referral center. PATIENT: A patient with biopsy-proven
      ganglionic hamartoma of the acoustic nerve was studied. INTERVENTION:
      Intervention consisted of surgical therapy. MAIN OUTCOME MEASURE: The main
      outcome measure was clinical evaluation. RESULTS: The result was successful
      removal of lesions with facial nerve preservation. CONCLUSIONS: An
      intracanalicular ganglionic hamartoma resulted in progressive sensorineural
      hearing loss and magnetic resonance imaging findings suggestive of small acoustic
      neuroma. This lesion, composed of an admixture of ganglion cells, fibroadipose
      tissue, and normal myelinated axons, although rare, should be added to the
      differential diagnosis of internal auditory canal lesions.

PMID- 9233493
TI  - Surgical anatomy of the transtemporal approaches to the petrous apex.
AB  - HYPOTHESIS: This study was undertaken to compare the subcochlear and
      infralabyrinthine approaches to the petrous apex. BACKGROUND: Both approaches are
      advocated to drain cholesterol granuloma or biopsy lesions of the petrous apex.
      There is little data directly comparing these approaches. METHODS: Anatomic
      dissections were performed on 20 preserved temporal bones. The anatomic distances
      were measured to the nearest quarter millimeter using a two-point needle caliper.
      Measurements were repeated three times and averaged. RESULTS: The average window
      created through the subcochlear approach was 9.41 x 7.33 mm. The approach is
      performed between the carotid artery, jugular bulb, and basal turn of the
      cochlea, and gives a roughly triangular window in most cases. The cochlear
      aqueduct and glossopharyngeal nerve may be exposed during this approach. The
      subcochlear approach provided a more consistent exposure (SD of 3.5 x 1.9) and
      was always possible. Still, the exposure obtained through this approach may be
      limited if the hypotympanic air cell tract is sclerotic. The infralabyrinthine
      approach gave adequate exposure in most cases, but a high-lying jugular bulb
      obstructed this approach completely in eight of 20 cases. The average window
      created was 4.99 x 7.23 mm (SD 4.4 x 1.3). CONCLUSIONS: The availability of a
      particular approach to the petrous apex and the exposure obtained varies
      considerably in individual cases. The choice of a surgical approach to the
      petrous apex should be influenced by the location of disease, the type of
      disease, the existing anatomy, and the experience of the surgeon.

PMID- 9233494
TI  - Facial nerve monitoring among graduates of the Ear Research Foundation.
AB  - OBJECTIVE: This study aimed to evaluate the patterns of facial nerve monitoring
      among graduates of an otology fellowship in which monitoring is emphasized
      throughout training. STUDY DESIGN: This study involved a questionnaire
      administered to graduates of the Ear Research Foundation, Sarasota, Florida,
      U.S.A. (otology/neurotology fellowship). SETTING: The study was performed in
      academic and private practices of surveyed physicians. MAIN OUTCOME MEASURES:
      These included patterns of facial nerve monitor use and surgical results after
      facial nerve injuries. RESULTS: Nearly 100% of the graduates of the Ear Research
      Foundation continue to use facial nerve monitoring routinely in otologic surgery.
      Five cases of facial nerve injury in surgery for long-term disease were reported
      for all 15 neurotologists surveyed. CONCLUSION: Routine facial nerve monitoring
      is not considered the standard of care in most communities; however risk of
      facial nerve injury appears to be greatly reduced when this adjunctive technique
      is employed.

PMID- 9233495
TI  - Surgical management of geniculate neuralgia.
AB  - BACKGROUND: Geniculate ganglion or nervus intermedius neuraigia is an unusual
      condition resulting in deep ear pain with or without signs of atypical trigeminal
      neuralgia, deep face, or throat pain. This article describes an experience with
      14 patients who came to the neurosurgical service at the University of Pittsburgh
      Medical Center with a diagnosis of geniculate neuralgia. METHODS: After failing
      conservative treatment and after undergoing neurologic, otologic, and dental
      evaluations, these 14 patients underwent 20 intracranial procedures consisting of
      retromastoid craniectomies with microvascular decompression of cranial nerves V,
      IX, and X with section of the nervus intermedius in most cases. RESULTS: At
      operation, vascular compression of the nerves and nervus intermedius was found,
      which implicated vascular compression as an etiology of this disorder. Initially,
      10 of 14 patients had an excellent outcome (71.5%), 3 experienced partial relief
      (21.5%), and there was 1 failure (7%). Ten patients were available for long-term
      (> 12 months) follow-up. Of these 10, 3 retained the excellent result (30%), 6
      experienced partial relief (60%), and there was 1 failure (10%). Complications
      included one transient facial paresis, one facial numbness, one paresis of
      cranial nerves IX and X, one chemical meningitis, two cerebrospinal fluid leaks,
      and one superficial wound infection. Of those that fell from the excellent to
      partial category, this usually involved a return of atypical facial pain, but
      otalgia remained resolved. CONCLUSIONS: Overall, good results (with excellent or
      partial relief) were found long term for 90% of patients in this series. The
      authors recommend microvascular decompression of cranial nerves V, IX, and X with
      nervus intermedius section for the treatment of geniculate neuralgia.

PMID- 9233496
TI  - Imaging case of the month: facial nerve neuroma.

PMID- 9233498
TI  - Normal hearing in acoustic neuroma patients: a critical evaluation.

PMID- 9233497
TI  - Clinical forum: a review of intratympanic therapy.
AB  - OBJECTIVE: This article provides an overview of the rational basis for the
      appropriate clinical use of intratympanic aminoglycosides and steroids. DATA
      SOURCES: The data sources were relevant English language clinical and basic
      science publications. STUDY SELECTION: The most recent publication available for
      each author or group of original, human, clinical reports about the technique
      were included. DATA EXTRACTION: The techniques and results for control of vertigo
      and hearing loss were compared. CONCLUSIONS: At least 11 articles have been
      published that indicate that intratympanic gentamicin treatments control vertigo
      well and provide acceptable rates of hearing loss. Intratympanic gentamicin
      should be the initial treatment of choice for unilateral disabling Meniere's
      disease that has failed medical therapy. The use of intratympanic steroids should
      remain investigational until more favorable data are available.

PMID- 9233499
TI  - Endolymphatic duct/sac enhancement on gadolinium magnetic resonance imaging of
      the inner ear: preliminary observations and case reports.

PMID- 9233500
TI  - Does computerized dynamic posturography help us care for our patients?

PMID- 9233501
TI  - The efficacy of trypsin for disinfection of in vitro fertilized bovine embryos
      exposed to bovine herpesvirus 1.
AB  - Bovine cumulus-oocyte complexes (COC) or in vitro fertilized (IVF) embryos were
      exposed to bovine herpesvirus 1 (BHV-1) during in vitro maturation or co-culture
      with uterine tubal cells, respectively. Trypsin, at a concentration of 0.25%, was
      applied (for approximately 90 s) to disinfect either COC or cumulus-free oocytes
      (CFO) 18 h after insemination, or on day 7 to embryos resulting from infected
      oocytes. In total, virus was not detected in 71% of 93 samples containing 233
      embryos exposed to BHV-1 and trypsin treatment. BHV-1 was detected in 14% and 54%
      of samples containing a single embryo and five embryos, respectively. In
      corresponding groups of embryos exposed to BHV-1, then washed but not treated
      with trypsin (70 samples), 85% and 96% of samples containing one embryo and
      pooled embryos, respectively, were positive for the virus. There was no effect of
      trypsin treatment on the development of IVF-embryos. It is concluded that IVF
      generated embryos have a greater tendency to carry BHV-1 after experimental
      exposure to the virus than IVF uterine stage embryos, and that they are more
      difficult to disinfect by means of the standard trypsin treatment use.

PMID- 9233503
TI  - Variation between ejaculates in the fertility of frozen ram semen used for
      cervical insemination of Merino ewes.
AB  - Two field experiments were conducted to investigate the amount of variation
      between rams, and between ejaculates within rams, in the fertility of frozen
      thawed semen used for cervical insemination. Individual ejaculates from seven
      Merino rams were frozen and used to cervically inseminate Merino ewes at a
      synchronized oestrus at two sites. In Experiment 1 (N = 491), pregnancy rates
      (determined 70-80 days after insemination) for individual rams ranged from 1.8 to
      11.9%. Individual ejaculates produced pregnancy rates between 0 and 21.4%.
      Overall conception rate was 6.5%. No significant differences were detected.
      Pregnancy rates for the same rams in Experiment 2 (N = 449) varied from 10.3 to
      32.6% (P < 0.05). Ejaculate pregnancy rates ranged between 0 and 60% (P < 0.01).
      Fertility of individual ejaculates within rams differed for three of the seven
      rams used (P < 0.01). It is concluded that considerable variation in fertility of
      frozen ram semen exists between ejaculates within rams as well as between rams.
      Possible sources (biological and arising from freezing artefacts) of such
      variation and their practical implications are discussed.

PMID- 9233502
TI  - Seasonal and acute heat stress effects on steroid production by dominant
      follicles in cows.
AB  - The present study concerned the seasonal and acute effects of heat stress on
      steroid concentrations in follicular fluid and on steroid production by granulosa
      and theca interna cells, in bovine dominant follicles. Three groups of cows were
      studied: summer (n = 5), autumn (n = 5) and winter (n = 9) cows. During the
      winter season, another group of cows was acutely heat-stressed from days 3
      through 5 of the estrous cycle (n = 5). On day 7 of the estrous cycle, follicular
      fluid from first-wave dominant follicles was aspirated, and dispersed granulosa
      and theca cells from each seasonal group were incubated for 18 h at normothermic
      (37.5 degrees C) or high (40.5 degrees C) temperatures. Cells were incubated in
      media only or in media containing testosterone (300 ng ml-1, for granulosa cells)
      or forskolin (4 micrograms ml-1, for theca cells). In follicular fluid the 17
      beta-estradiol concentration was high (P < 0.05) in winter and low in autumn, and
      summer, the androstenedione concentration was high in summer (P < 0.05), low in
      autumn, and intermediate in winter. During the winter season, acute in vivo heat
      stress increased follicular fluid androstenedione and decreased estradiol to
      levels comparable with those prevailing in summer. Basal and forskolin-stimulated
      androstenedione production by theca cells was higher (P < 0.05) in the winter
      group than in the summer and autumn groups, and also higher than in the cows that
      were heat-stressed during winter, which suggests that theca cell function is
      susceptible to chronic (summer), short-term (winter) and delayed (autumn) heat
      stresses. In vitro incubation at high temperature (40.5 degrees C) reduced the
      high, forskolin-stimulated androstenedione production in winter (P < 0.05).
      Estradiol production by granulosa cells was high in winter and autumn, and low in
      summer (P < 0.05). Acute heat stress in winter did not alter estradiol production
      relative to winter controls, whereas a high incubation temperature (40.5 degrees
      C) reduced (P < 0.05) estradiol production only in the autumn, when the highest
      production rate was recorded. The results indicate a differential effect of heat
      stress on the functions of granulosa and theca cells. Both concurrent and delayed
      effects of heat stress on the steroidogenic capacity of ovarian follicles in
      cattle are presented.

PMID- 9233504
TI  - Method of stimulating ovulation rate in Merino ewes may affect conception but not
      embryo survival.
AB  - Efficiency in breeding flocks can be improved by increasing twinning rate. While
      this can be achieved by several methods that stimulate ovulation rate, there is
      considerable variation in the number of extra lambs produced by alternative
      treatments. Variations in ovulation rate following stimulation treatments are
      well documented, but the subsequent processes of conception and embryo survival
      leading to extra lambs are not. Differences in lambs produced by four alternative
      stimulation treatments examined in the following experiments were not
      significantly affected by embryo survival. The stimulation treatments examined
      were: improved nutrition for several weeks pre-mating (N); lupins (L) as stubble
      or standing crop, or fed as grain; grazed tagasaste forage (T); Fecundin
      immunisation (F). Ovulation rates were measured using laparoscopy and viability
      of embryos monitored using ultrasound. Ovulation rates in treated groups were
      increased by up to 0.66 (L), 0.20 (T), 0.10 (N) and 0.36 (F) ova per ewe.
      Survival of twin ova in pregnant ewes ranged from 81 to 93% across treatments and
      flocks, but did not differ significantly between treatments within flocks.
      Proportions of ewes pregnant in the first cycle of mating were depressed by 8-11%
      in F and L treatments. Conception rates were higher (by 7-16%) in twin rather
      than single ovulating ewes, and, in one flock, higher (by 15%) following
      bilateral rather than unilateral twin-ovulations. All stimulation treatments
      increased numbers of lambs conceived, lupins being the most efficient.
      Differences between treatments in lambs conceived were dependent on ovulation and
      conception rates but not embryo survival. Rates of embryo survival that were
      similar between treatments, but differed between flocks, indicated failure due to
      maternal factors rather than the embryos themselves. The mechanism(s) responsible
      could not be determined in these experiments, but genetic differences between
      flocks are suggested.

PMID- 9233505
TI  - Short-term studies of ovarian metabolism in the ewe.
AB  - The ovarian uptake of metabolites in anaesthetised ewes was determined. In both
      studies, catheters were inserted into the ovarian vein and femoral artery, and
      Transonic flow transducers were placed around the ovarian arterio-venous plexus.
      Arterio-venous differences in glucose, lactate, free fatty acids (FFA), 3
      hydroxybutyrate (3-OHB), acetate, cholesterol and progesterone and oestradiol-17
      beta levels were determined every 10 min over a 3.5 h period. In study one,
      glucose uptake was significant in three sheep, and one sheep only had a
      significant uptake of FFA. Ovarian 3-OHB uptake was significant in two sheep.
      significant uptake of acetate or cholesterol was identified in one sheep.
      Progesterone secretion was significant in three sheep and two sheep had
      significant progesterone uptake. In study 2, glucose uptake was significant in
      four sheep and lactate release was significant in the same sheep. There was
      uptake of FFA and 3-OHB, cholesterol, and acetate in each of three different
      sheep. Oestradiol-17 beta output was significant for sheep in oestrus and
      prooestrus. While the effects of gonadotrophin-releasing hormone (GnRH) treatment
      were confounded by time spent under anaesthesia, exogenous GnRH appeared to have
      no significant effect on the uptake of most metabolites and steroid hormone
      outputs. The metabolic requirements for energy and precursors for progesterone
      was small. Glucose was the major source of energy for the ovary and appears to be
      metabolised through anaerobic pathways, as indicated by significant lactate
      output.

PMID- 9233506
TI  - Level of nutrition modulates the dynamics of oestradiol feedback on plasma FSH in
      ovariectomized ewes.
AB  - The frequency of multiple ovulations in mature, cyclic ewes is strongly
      influenced by the level of nutrition, but it is difficult to demonstrate
      concurrent changes in plasma concentrations of gonadotropins. The failure to do
      so might be a consequence of rapid compensation by the homeostatic feedback
      mechanism linking secretion by the hypothalamus/pituitary gland and ovarian
      hormones. Most experimental models have examined the components of the
      homeostatic feedback system after steady state relationships had been
      established. We hypothesised that the effects of nutrition might be observed more
      readily if the system were disrupted and then examined while equilibrium was
      being re-established. This hypothesis was tested in three experiments in Merino
      ewes by allowing gonadotropin secretion to escape feedback for 5 days after
      ovariectomy and then replacing ovarian hormones and examining effects of feeding
      regimen on the return of plasma concentrations of FSH to baseline values. In all
      three experiments, oestrogen replacement caused plasma concentrations of FSH to
      decline more rapidly (P < 0.05) in ewes fed at 0.5x maintenance, than in ewes fed
      at 1.4x maintenance, with groups fed at maintenance being intermediate. No effect
      of diet was observed on plasma FSH concentrations in the absence of oestradiol,
      and neither progesterone nor charcoal-treated bovine follicular fluid influenced
      the effect of nutrition. Plasma concentrations of oestradiol were 9.8% lower on
      average (NS) in ewes fed above maintenance than in the sheep fed below
      maintenance over the three experiments, suggesting that there may have been a
      reduced clearance of oestradiol which contributed to the result. We conclude that
      feeding regimen affects the secretion or clearance of gonadotropins in mature
      ewes, as in the mature ram, and that this is one mechanism by which ovulation
      rate may be affected.

PMID- 9233507
TI  - Dietary excesses of urea influence the viability and metabolism of
      preimplantation sheep embryos and may affect fetal growth among survivors.
AB  - In the first of two experiments investigating the effect of dietary urea on the
      survival and metabolism of ovine embryos, 30 Border Leicester x Scottish
      Blackface ewes received a maintenance diet (milled hay, molasses, minerals,
      vitamins) with no urea (control, C; n = 10) or with added urea at 15 g (low urea,
      LU; n = 10) or 30 g (high urea, HU; n = 10) kg-1 feed for a 12 week period. The
      degraded nitrogen (N) status relative to estimated rumen microbial N requirements
      was -2, +9 and +20 g per day, respectively. One week after allocation to diets,
      progesterone priming (12 days) commenced. Ewes received 800 IU of equine
      chorionic gonadotrophin at progesterone withdrawal, were inseminated 52 h later
      (Day 0) and embryos were collected from five ewes per group at Day 4 and from
      five ewes at Day 11. If available, one embryo was returned to each ewe; the rest
      were cultured in vitro. There was no effect of treatment on progesterone,
      luteinizing hormone (LH), or time of oestrus onset C, LU and HU plasma urea (P <
      0.001) and ammonia levels (C vs. HU, P < 0.01; LU vs. HU, P < 0.05) differed. Day
      4 HU embryos were retarded relative to C and LU embryos. After 3 days of culture,
      70%, 66% and 0% of C, LU and HU embryos, respectively, were viable. Mid-term
      pregnancy rates following transfer were 63%, 43% and 33%. Only one HU lamb (male)
      was born following embryo transfer, its birthweight (10.1 kg) exceeded that of
      its C (n = 3; 7.0, 7.0, 7.5 kg) and LU (n = 2; 7.3, 8.2 kg) counterparts (P <
      0.025). In the second experiment, C2 (2.5 g urea kg-1; n = 5) and HU2 (30 g kg-1;
      n = 7) diets which provided similar intakes of degraded N relative to microbial
      requirements as those for C and HU ewes in Experiment 1 were fed to Border
      Leicester x Scottish Blackface ewes superovulated with 16 mg of porcine follicle
      stimulating hormone. Urea and ammonia levels in utero-oviductal samples were
      elevated in HU2 ewes (P < 0.05). At collection (Day 3), HU2 embryos used more
      glucose (P < 0.01) and, following culture, some exhibited up to a 2.8-fold
      increase in metabolism. In conclusion, excess rumen degradable N in ewe diets
      elevates urea and ammonia in plasma and in utero, with an associated increase in
      embryo mortality. Nevertheless, metabolism appears to be up-regulated in some
      embryos and, among those that survive, fetal growth appears to be enhanced.

PMID- 9233508
TI  - Some effects of adding p-LH in defined amounts to purified p-FSH to modify FSH/LH
      ratios during the superovulatory treatment of anestrous ewes.
AB  - Nonlactating Leccese ewes (n = 61) were used during seasonal anestrus to
      investigate the effects on ovarian response and embryo production of adding
      defined amounts of p-LH to purified p-FSH as well as decreasing the FSH/LH ratio
      during treatment. The ewes were synchronized with FGA-impregnated intravaginal
      pessaries for 9 days and prostaglandin F2 alpha (Cloprostenol) injected on the
      seventh day. They were divided into six treatment groups in a 3 x 2 factorial
      design: three amounts of purified p-LH (100, 50 or 25% equivalent to 525, 262 or
      131 IU p-LH) x 2 regimen of p-FSH and p-LH administration (constant or decreasing
      FSH/LH ratio). Each ewe received a total of 525 IU p-FSH at a decreasing dose,
      twice daily over a 3-day period. Group I (n = 11), Group II (n = 10) and Group
      III (n = 10) were treated with p-FSH supplemented with p-LH at 100%, 50% and 25%,
      respectively, of p-FSH dose and a constant FSH/LH ratio throughout the treatment
      period. Group IV (n = 10), Group V (n = 10) and Group VI (n = 10) were treated
      with p-FSH supplemented with p-LH at 100%, 50% and 25%, respectively, of p-FSH
      dose but with a decreasing FSH/LH ratio over the 3 days of the treatment: 1.7
      0.86-0.43 for Group IV; 3.4-1.7-0.86 for Group V; 6-3-1.5 for Group VI. Embryos
      were flushed surgically on Day 6 after estrus. The ovulation rate did not differ
      among the groups (8-12.8). Superovulation with 100% p-LH and decreasing the
      FSH/LH ratio (Group IV) resulted in: (i) the highest ova recovery (9.8 +/- 1.7),
      and this was significantly different (P < 0.05) from the 25% p-LH treated group
      (Group VI; 5.0 +/- 1.7), (ii) the highest fertilization rate (90.6 +/- 9.2%),
      with a significant (P < 0.01) difference compared with the constant ratio regimen
      (Group I; 62.6 +/- 8.3%); (iii) the highest transferable embryo yield (6.4 +/-
      1.1), differing significantly (P < 0.01) from Group VI (2.2 +/- 1.1) and Group I
      (2.7 +/- 1.0). It is concluded that decreasing the amount of p-LH added to
      purified p-FSH did not improve the superovulatory response of ewes during the
      anestrous period. Transferable embryo production was significantly improved when
      ewes were treated with p-LH equivalent to 100% p-FSH, with the FSH/LH ratio
      decreasing during treatment.

PMID- 9233509
TI  - A comparison of two methods of oestrous synchronisation of hair sheep in the
      tropics.
AB  - Two trials were conducted to evaluate the efficacy of oestrous synchronisation
      procedures in St. Croix White, Barbados Blackbelly hair and Florida Native wool
      ewes. In Trial 1 (conducted in June), 27 ewes were treated with controlled
      internal drug release (CIDR) devices for 12 days (CIDR1) and 29 untreated ewes
      served as controls (CONT). The CIDR devices were removed on the same day that
      intact rams equipped with marking harnesses were placed with the ewes. Time to
      oestrus after ram introduction was shorter (P < 0.0001) in CIDR1 than CONT ewes.
      Within 3 days of ram introduction 100% of CIDR1 ewes but only 37.9% of CONT ewes
      had been in oestrus (P < 0.0001). Conception rate at first oestrus after ram
      introduction was 74.1% overall, with no effect (P > 0.10) of treatment, but days
      to conception were shorter (P < 0.001) in CIDR1 than CONT ewes. Ovulation rate at
      first oestrus after ram introduction was not different (P > 0.10) between CIDR1
      and CONT ewes. The CIDR1 ewes lambed earlier (P < 0.004) in the lambing season
      than CONT ewes, but there was no difference in the number of lambs born per ewe
      (P > 0.10). In Trial 2 (conducted in October), 14 St. Croix White ewes were
      treated with CIDRs as in Trial 1 (CIDR2) and 14 St. Croix White ewes were given
      two i.m. injections (15 mg) of prostaglandin F2 alpha (PGF) 10 days apart. Intact
      rams were introduced on the day of CIDR removal or the second PGF injection. The
      CIDR2 ewes exhibited oestrus earlier (P < 0.01) than PGF treated ewes. The
      conception rate to breeding at the synchronised oestrus was similar (P > 0.10)
      between CIDR2 and PGF treated ewes. Progesterone concentration on Day 10 after
      the synchronised oestrus was not different (P > 0.10) between CIDR2 and PGF
      treated ewes. These results indicate that oestrous synchronisation procedures can
      be used in sheep in the tropics without adversely affecting fertility. Due to a
      lack of seasonal anoestrous these procedures have the potential to be used during
      all times of the year.

PMID- 9233510
TI  - Effect of service on duration of oestrus and ovulation in dairy goats.
AB  - In the autumn, Nubian goats (n = 24) were randomly divided into two equal groups
      after oestrus had been synchronized using fluorogestone acetate intravaginal
      pessaries (FGA, 30 mg) over a 20 day period. The onset of oestrus was detected at
      8 h intervals using either of two vasectomized bucks fitted with an apron during
      the 5 days following pessary removal. A buck was permitted to mount and serve
      each doe only twice in 30 min within the first 8 h of oestrus initiation in the
      SER group. In the CON group, a buck was only permitted to mount. Ovulation was
      determined by laparoscopy at 8 h intervals starting 24 h after onset of oestrus.
      Duration of oestrus for SER and CON groups was (mean +/- SD) 26.7 +/- 7.1 and
      36.0 +/- 8.0 h, respectively (P < 0.01). The first and last ovulations for SER
      and CON groups were 34.7 +/- 3.9 and 37.3 +/- 6.2 h, and 35.3 +/- 5.4 and 38.0 +/
      6.0 h from oestrus initiation, respectively (P > 0.05). No differences were
      found between right and left ovarian activity (P > 0.05). Ovulation rates did not
      differ (2.17 +/- 0.58 and 2.17 +/- 0.94). Ovulations occurred principally towards
      the end of oestrus in the CON group and after oestrus had ended in the SER group.
      Service reduced the duration of oestrus without affecting ovulation times or
      ovulation rates in Nubian dairy goats.

PMID- 9233511
TI  - Early pregnancy diagnosis in alpaca (Lama pacos) and llama (Lama glama) by
      ultrasound.
AB  - An ultrasonography study of early pregnancy diagnosis was carried out in 19
      alpacas and 12 llamas, after controlled matings. The aim was to determine the
      earliest gestational age at which pregnancy diagnosis by transrectal
      ultrasonography could be achieved, and to generate an empirical formula for
      gestational sac diameter (GSD) growth as a function of gestational age (GA),
      allowing an estimate of GA during the first month of pregnancy. We found that
      pregnancy diagnosis may be carried out as early as 9 days after mating in alpacas
      and 7 days in llamas. This diagnosis was found to be accurate at 23 days in
      alpacas and 34 days in llamas. The empirical relations that best describe the
      relationship between GSD and GA were GA = logGSD + 1.2339/0.0585 r = 0.85; P <
      0.001 in alpacas, and GA = logGSD + 1.2649/0.0546 r = 0.77, P < 0.001 in llamas,
      where GA is measured in days and GSD in centimeters. Our results also indicate
      that ultrasonography is a reliable technique for early pregnancy diagnosis.
      Furthermore, the empirical formulae reliably make it possible to estimate GA from
      GSD during the first month of pregnancy and their use might improve the
      efficiency of camelid breeders.

PMID- 9233512
TI  - Short-term effects of exogenous estradiol-17 beta on blastocyst development
      during the period of elongation in swine.
AB  - Objectives were to examine the effects of a single dose (4 mg) of estradiol-17
      beta (E2) on blastocyst development around the period of elongation. Proestrus
      gilts were induced to ovulate with 750 IU of hCG and were mated before ovulation
      (normal mating, 24 to 32 h post-hCG) or after ovulation had begun (delayed
      mating, 43 h post-hCG). This difference in time of mating has been demonstrated
      to result in approximately a 7-h difference in time of blastocyst elongation.
      Normally and delay-mated gilts were ovariohysterectomized at 278 h post-hCG or
      injected with E2 or vehicle (corn oil) at 278 h and then ovariohysterectomized at
      290 h post-hCG (five or six gilts per group). Blastocyst size was measured and
      concentrations of E2, retinol, uteroferrin, insulin-like growth factor-I (IGF-I),
      uterine plasmin/trypsin inhibitor (UPTI) and protein in uterine flushings were
      quantified. Blastocyst size and components of uterine flushings did not differ (P
      > 0.05) between normally and delay-mated gilts at 278 h post-hCG. However, at 290
      h post-hCG, normally mated gilts had larger (P < 0.01) blastocysts (small spheres
      to filamentous) and their flushings tended to contain less (P < 0.07) amounts of
      retinol than those of delay-mated gilts whose blastocysts ranged from small
      spheres to ovoidals. Normally mated gilts receiving E2 at 278 h had smaller (P <
      0.01) blastocysts and less (P < 0.05) amounts of retinol at 290 h post-hCG than
      gilts receiving vehicle. Conversely, delay-mated gilts treated with E2 or vehicle
      did not differ (P > 0.05) in blastocyst size and amounts of components of uterine
      flushings at 290 h post-hCG. Normally mated gilts treated with vehicle had
      litters in the process of elongating at 290 h post-hCG. Mean blastocyst size (P <
      0.001) and amounts of components of uterine flushings (except for IGF-I) in these
      gilts were greater (P < 0.05, UPTI = 0.06) than in normally mated gilts at 278 h
      post-hCG, whose blastocysts were spherical. Among gilts not treated with E2 (278
      h and 290 h pooled), mean blastocyst size was positively correlated (P < 0.05)
      with amounts of retinol, E2, uteroferrin and total protein. Results indicated
      that a single dose of E2 given before elongation altered blastocyst development
      depending on how close blastocysts were to onset of elongation at the time of E2
      treatment.

PMID- 9233513
TI  - Changes in sperm ultrastructure and localisation in the porcine oviduct around
      ovulation.
AB  - Changes in the morphology and localisation of spermatozoa in the utero-tubal
      junction (UTJ) and three equal segments of the isthmus (lower, middle and upper
      isthmus) within +/-8 h of ovulation were studied with scanning and transmission
      electron microscopy. Spermatozoa were located at specific sites within the UTJ
      isthmic environment. Two sperm subpopulations were evident, one with epithelial
      contact and one without such contact. Most of the sperm population with
      epithelial contact maintained intact plasma membrane during the pre-ovulatory
      period and showed acrosome reacted-like membrane changes during the post
      ovulatory period. In contrast, plasma membranes in most of the spermatozoa with
      no epithelial contact were already broken before ovulation. Ovulation was also
      accompanied by a relocation of spermatozoa from the mucosal crypts/interfolds
      towards the more central part of the mucosal surface.

PMID- 9233514
TI  - Sperm head morphometry analysis of ejaculate and dismount stallion semen samples.
AB  - The evaluation of seminal characteristics is important in the clinical detection
      of stallion subfertility. Conventional semen evaluation includes subjective
      determination of sperm concentration, motility, and gross morphology. Due to the
      subjectivity and variability of the manual morphology assessment, computer
      automated sperm morphology analyses has been developed. Computer automated sperm
      morphology analysis was applied in the current study to determine if the
      morphometric measurements of sperm heads from collected and dismount samples of
      the same ejaculate were similar. If the post-ejaculate dismount sample is
      representative of the entire ejaculate, this sample may be utilised in
      determining the fertility of the ejaculate. Ejaculate samples were collected from
      ten stallions using an artificial vagina. Post-ejaculate dismount samples of the
      same ejaculate were taken from the head of the penis. A thin smear of the
      collected and dismount samples were prepared onto microscope slides and
      spermatozoa were stained for 40 min in haematoxylin. At least 200 properly
      digitised sperm heads from each slide were analysed using computer automated
      sperm morphometry analysis. The mean values for length, width, width/length,
      area, and perimeter were recorded from each analysis of collected and dismount
      samples and compared by paired t-test. The coefficients of variation of each
      analysis was also recorded and compared between collected and dismount samples by
      paired t-test. No significant differences (P > 0.10) in any measurements were
      found between collected and dismount samples. The mean values for all stallions
      for collected and dismount samples were length = 5.96 microM and 6.06 microM,
      width = 2.95 microM and 2.98 microM, width/length = 0.49 and 0.49, area = 13.31
      microM2 and 13.65 microM2 and perimeter = 15.54 microM and 15.74 microM
      respectively. No significant differences were detected in the coefficients of
      variation of sperm head measurements from collected and dismount samples. These
      results indicate sperm head measurements from dismount semen are representative
      of those of the ejaculate. Hence, sperm head measurements of dismount samples may
      be viably applied to studies of fertility or in case of clinical fertility
      assessment. This finding will further assist in the development of normal sperm
      head morphometry criteria in the stallion. Clinically, a slide can be prepared in
      the field after natural services matings and analysed accurately and objectively
      by ASMA.

PMID- 9233515
TI  - Changes in plasma luteinizing hormone, testosterone and estradiol-17 beta levels
      and semen quality after injections of gonadotropin releasing hormone agonist and
      human chorionic gonadotropin in three dogs with oligozoospermia and two dogs with
      azoospermia.
AB  - Plasma luteinizing hormone (LH) and testosterone (T) levels in three normal male
      Beagles increased markedly, the LH levels peaking at 30 or 45 min and the T
      levels at 45 or 60 min respectively, after a subcutaneous injection of 1
      microgram kg-1 gonadotropin releasing hormone agonist (GnRH-A). Two Collies and a
      Great dane diagnosed as oligozoospermic and two Shetland sheep dogs diagnosed as
      azoospermic by evaluation of semen quality were treated with 1 microgram kg-1
      GnRH-A after blood collection. Their plasma levels of LH, T and estradiol-17 beta
      (E2) were measured by radioimmunoassay for the purpose of investigating the
      effect of hormone therapy on spermatogenic dysfunction and the mechanism on
      improvement of semen quality. The semen quality of one of the Collies had
      improved 4 weeks after the GnRH-A treatment. The dog was treated with GnRH-A
      again and mated with a bitch 4 days later. The bitch gave birth to five puppies.
      The other dogs, whose semen quality had not improved, were treated with an
      intramuscular injection of 500 or 1000 IU human chorionic gonadotrphin (hCG) per
      animal. Since the semen quality of the other Collie and the Great Dane improved
      temporarily 2 and 4 weeks, respectively, after hCG treatment, the former was
      mated with a bitch 5 days later. The bitch gave birth to a litter of seven
      puppies. These hormone treatments, however, had no effect on the azoospermia in
      the two Shetland sheep dogs. Although the mean plasma LH and T levels in the dogs
      with oligozoospermia had been low, their LH levels gradually increased after
      hormone treatment. There were no marked changes in plasma T or E2 levels. These
      findings indicate that the semen quality of dogs with oligozoospermia can be
      temporarily improved between 2 and 4 weeks after a single injection of GnRH-A or
      hCG and the fertility of the dogs restored by the injection.

PMID- 9233516
TI  - Chemotherapy for advanced pancreatic cancer--some light at the end of the tunnel?

PMID- 9233517
TI  - Does chemotherapy for head and neck cancer improve symptoms?

PMID- 9233518
TI  - Does surgery belong to medical history for gastric lymphomas?

PMID- 9233519
TI  - Adrenocortical carcinoma.

PMID- 9233520
TI  - Cell signaling and cancer treatment.

PMID- 9233521
TI  - Should subjects who used psoralen suntan activators be screened for melanoma?
      Epidemiology and Prevention Subgroup, EORTC Melanoma Cooperative Group EORTC
      Prevention Research Division.
AB  - BACKGROUND: Psoralens are potent tanning activators that have been introduced in
      France and in Belgium in some tanning lotions and sunscreens. It was shown that
      poor tanners who ever used psoralen tanning activators display a four-fold
      increase in melanoma risk when compared to poor tanners using regular sunscreens.
      Although psoralens have now banned from suntan lotions, it is likely that the
      increase in melanoma risk linked to their previous use will persist for several
      years. METHODS: The melanoma risk attributable to psoralens use was calculated to
      evaluate the population at risk in France and Belgium. RESULTS: Melanoma
      incidence for the year 1995 was estimated to be of 10.2 per 100,000 in France and
      of 10.0 per 100,000 in Belgium, representing 5,900 and 1,000 melanoma cases. From
      the melanoma incidence among poor tanner who ever used psoralens (52 per 100,000)
      and estimation of the percentage of psoralen users among poor tanners, it can be
      derived that, for the year 1995, 267 melanoma cases could be attributed to
      psoralen tanning activators. CONCLUSIONS: Subjects who used psoralen suntan
      activators should be informed of their increased melanoma risk and be encouraged
      to participate in clinical programmes for early detection of melanoma, more
      especially when they are poor tanners and display a high naevi count. Such an
      action could save a significant number of lives.

PMID- 9233522
TI  - Treatment of advanced pancreatic carcinoma with a combination of protracted
      infusional 5-fluorouracil and weekly carboplatin: a Mid-Atlantic Oncology Program
      Study.
AB  - BACKGROUND: Advanced pancreatic cancer is a rapidly fatal disease whose course
      has been little influenced by chemotherapy. Earlier studies have shown some
      modest promise for the combination of protracted infusional 5-fluorouracil (PIF)
      and cisplatin. We sought to evaluate a regimen of possibly lesser toxicity, PIF
      plus weekly carboplatin. PATIENTS AND METHODS: Fifty-four patients with advanced
      adenocarcinoma of the pancreas were treated with a regimen of protracted
      infusional fluorouracil 300 mg/m2/day for 70 days and carboplatin 100
      mg/m2/weekly on weeks 1 through 10 of a 12-week cycle. After a two-week rest,
      cycles were repeated until progression. RESULTS: Median duration on treatment was
      82 days (range 4-490 days). Toxicity was mild. Grade 3-4 toxicities were anemia
      11%, leukopenia 6%, thrombocytopenia 2%, nausea/ vomiting 7%, diarrhea 9%,
      mucositis 9%, and renal 2%. Response was evaluable in 47 patients. There were two
      complete and seven partial responses (17% overall objective response rate among
      all patients). Stable disease for greater than 12 weeks was seen in 19 patients
      (40%) and progression in 19 (40%). The median overall survival was 22 weeks (1
      99), with 61 weeks median survival in responders (22-99). One-year survival was
      13%. CONCLUSIONS: Response and survival results with this regimen are at least
      equal to the best combination regimens reported, and were obtained with a low
      overall rate of serious toxicity.

PMID- 9233523
TI  - Chemotherapy for symptom control in recurrent squamous cell carcinoma of the head
      and neck.
AB  - BACKGROUND: The role of chemotherapy in patients with recurrent squamous cell
      carcinomas of the head and neck (SCCHN) is unclear. The aim of this study was to
      assess the ability of combination chemotherapy to control symptoms in this
      setting. PATIENTS AND METHODS: Using a prospectively accrued database all
      patients referred for chemotherapy with symptomatic relapse following surgery
      were identified. Objective response was recorded using standard criteria and
      maximum symptom response was assessed retrospectively from case notes using a
      published scoring scale. RESULTS: A total of 57 (median age 56, range 37-85)
      patients were studied who had received mainly cisplatin/5-fluorouracil
      combinations. Thirty-seven had previously received radiotherapy. Fifty-two
      patients had evaluable disease; 18 (35%) had objective responses (14 PRs and 4
      CRs). There were a total of 103 symptoms recorded with eight different individual
      symptoms. Forty-four (43%) symptoms improved on treatment, 52 (50%) were
      unchanged and 7 (7%) worsened. The number of patients with improvement in the
      most frequently recorded symptoms were as follows: pain 11/28 (39%), swelling
      12/23 (52%) and dysphagia 6/18 (33%). Sixty-seven percent of patients with
      objective response also had an improvement in their symptoms but a significant
      proportion (33%) of non-responders had a symptomatic response. Lack of objective
      response was not correlated with worsening symptoms. Grade 3/4 toxicity was
      uncommon (6%-17%) and there were no toxic deaths. A majority of patients (82%)
      experienced either no change or an improvement in performance status. CONCLUSION:
      These results demonstrate that chemotherapy improves many of the symptoms
      associated with recurrent SCCHN, without deterioration in performance status.
      Symptomatic improvement is more likely if there is evidence of significant tumour
      shrinkage, but even non-responding patients can benefit.

PMID- 9233524
TI  - Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of
      nasopharynx and other sites of the head and neck. A phase II study conducted by
      the Hellenic Cooperative Oncology Group.
AB  - BACKGROUND: Paclitaxel has been demonstrated to have significant activity in
      recurrent or metastatic head and neck cancer (HNC). In addition, the combination
      of paclitaxel and cisplatin is active in untreated patients with inoperable HNC.
      Substitution of carboplatin for cisplatin allows the treatment to be delivered on
      an outpatient basis. PURPOSE OF THE STUDY: To evaluate the activity and toxicity
      of the combination of paclitaxel by three-hour infusion and carboplatin as first
      line chemotherapy in patients with recurrent or metastatic HNC. PATIENTS AND
      METHODS: From March 1994 until August 1996, 49 patients with recurrent or
      metastatic HNC were treated with paclitaxel (200 mg/m2, by three-hour infusion)
      followed by carboplatin at an AUC of 7 mg.min/ml, every four weeks. G-CSF was
      administered prophylactically on days 2 to 12 of each cycle. There were 41 men
      and 8 women with a median age of 57 years (range 23-73). The majority of the
      patients were symptomatic and they had recurrent disease locoregionally. Fourteen
      patients had nasopharyngeal cancer (NPC) and 35 had squamous cell cancers of
      other areas of the head and neck region (non-NPC). RESULTS: At the completion of
      treatment, two patients with NPC demonstrated complete and six partial responses
      for an overall response rate of 57% (95% CI 29%-82%). Among patients with non
      NPC, the response rate was 23% (95% CI 9%-37%). After a median follow up period
      of 15 months, the median time to progression was 4.3 months in the non-NPC group
      and 16.5 months in the NPC group. At the time of the analysis, median survival
      had not been reached in NPC while it was 7.3 months in non-NPC patients. Grade 3
      4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, stomatitis,
      nausea/vomiting and diarrhea (4% each). CONCLUSIONS: The combination of
      paclitaxel and carboplatin appears to be well tolerated but only moderately
      active in patients with advanced non-NPC of the head and neck region. However,
      its activity appears promising in NPC and deserves further investigation.

PMID- 9233525
TI  - Decrease of interleukin-2 secretion is a new independent prognostic factor
      associated with poor survival in patients with small-cell lung cancer.
AB  - BACKGROUND: We have previously shown that suppression of interleukin-2 (IL-2)
      secretion was mediated by transforming growth factor (TGF) beta 1 secreted by
      small-cell lung cancer (SCLC) tumor cells. We have also shown that IL-2 secretion
      was significantly impaired in patients with SCLC at the time of diagnosis.
      Reconstitution of cytokine secretion correlated with reduction of tumor load.
      These data suggested that the immune system was suppressed by the tumor. To
      address the clinical relevance of cytokine suppression in SCLC, we investigated
      the correlation of the level of IL-2 secretion with survival. PATIENTS AND
      METHODS: The significance of correlations between single parameters in the test
      groups was calculated by using the linear regression analysis, the Wilcoxon rank
      sum test and the exact test according to Fisher. Using the Kaplan-Meier method,
      the log-rank test and the Cox-regression model, we analysed the relation of IL-2
      secretion in whole blood cell cultures from 52 patients with SCLC at the time of
      diagnosis to established prognostic factors relevant for survival in SCLC.
      RESULTS: Impairment of IL-2 secretion significantly correlates to survival in
      SCLC (P = 0.004). Further univariate and multivariate analysis showed that this
      prognostic factor is independent from other factors of prognostic relevance in
      SCLC, namely stage of disease, neurone specific enolase (NSE), lactate
      dehydrogenase (LDH), age, and sex. More important, the prognostic value of IL-2
      secretion is comparable to the most predominant prognostic factors for survival
      in SCLC identified so far. In the final model of the cox regression analysis, the
      P-value for IL-2 secretion in relation to stage of disease was 0.012 and 0.019,
      respectively. CONCLUSIONS: IL-2 secretion at the time of diagnosis represents an
      independent prognostic factor for survival in SCLC. Although its prognostic value
      has to be confirmed in a larger group of patients, our results demonstrate that
      IL-2 secretion may play an important role in diagnosis and treatment of SCLC.
      Moreover, in contrast to other prognostic factors, impairment of IL-2 secretion
      may help to understand immunosuppression in SCLC and, thus, important elements of
      the pathogenesis of this disease.

PMID- 9233526
TI  - Experience with independent radiological review during a topotecan trial in
      ovarian cancer.
AB  - BACKGROUND: The results of phase II clinical trials are usually based on response
      of tumours to new oncolytic agents as evidenced by radiological imaging
      techniques. In this trial, all claimed responders were reviewed at a specially
      convened meeting by the peer group of study investigators and a radiologist,
      independent of the study institutions. PATIENTS AND METHODS: One hundred eleven
      patients with advanced epithelial ovarian cancer who had previously been treated
      with a platinum based regimen and had subsequently relapsed and who had
      measurable disease were treated with topotecan at a dose of 1.5 mg/m2/day i.v. on
      five consecutive days repeated every 21 days to assess efficacy and tolerability.
      Ninety-three were considered eligible for the study per protocol and lesions were
      assessed by either computerised tomography (CT) or ultrasound (US). At the
      meeting, scans from all 24 (25.8%) claimed responders were reviewed, lesions
      remeasured by the radiologist and a group discussion led to a final response
      classification. RESULTS: Ninety-two patients were found to be eligible for the
      study and 14 (15.2%) were confirmed as responders. Ten were rejected as
      responders, mainly because the lesion did not decrease in size by < or = 50%, but
      one patient failed to meet the entry criteria. Remeasurement of CT scans was more
      objective than US scans. Difficulties were encountered during review of some CT
      scan sequences because of non-uniform imaging parameters. CONCLUSIONS:
      Independent radiological review in conjunction with the peer review group in this
      trial enabled rigorous and consistent application of response criteria. This
      decreased the response rate from 25.8% to 15.2%, but this represents a more
      objective assessment. CT scanning is an objective technique for assessing
      response rates in phase II studies whereas US is subjective and dose not
      necessarily allow accurate lesion assessment on subsequent examinations, nor
      allows independent review at a later date. For these reasons it should not be
      used in such studies for accurate lesion assessment. Cross-sectional imaging
      techniques such as CT and magnetic resonance imaging (MRI) do allow accurate
      lesion assessment and independent review at a later date, but standard protocols
      need to be instituted, to allow consistency and a comparison to be made with
      subsequent studies using the same agent and a broad comparison to be made with
      other agents.

PMID- 9233527
TI  - The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index
      provides independent information on overall survival of ovarian carcinoma
      patients.
AB  - BACKGROUND: The prognostic implications of p53 accumulation, bcl-2
      immunoreactivity and tumour proliferative fraction in ovarian carcinomas are
      still debated. PATIENTS AND METHODS: One hundred twelve ovarian carcinomas were
      immunostained for p53 protein, for bcl-2 and for the cell cycle-associated Ki-67
      antigen. The immunostaining results were correlated with conventional clinico
      pathological variables, response to induction chemotherapy, and patient survival.
      RESULTS: p53 accumulation and bcl-2 immunoreactivity in more than 10% of
      neoplastic cells were detected in 61 (54.5%) and 42 (37.5%) cases, respectively.
      A positive correlation between p53 accumulation and high (more than 30%
      neoplastic cells) MIB1 labelling index (r = 0.235; P = 0.015) was ascertained,
      whereas no significant association was found between bcl-2 immunoreactivity and
      p53 accumulation or MIB1 labeling index. Both p53 accumulation and MIB1
      immunoreactivity correlated significantly with a reduced overall survival, but
      the association was lost in multivariate analysis. However, patients with tumours
      simultaneously showing p53 accumulation and MIB1 labelling index higher than 30%
      had significantly reduced overall survivals, in both univariate and multivariate
      analyses. CONCLUSION: The simultaneous evaluation of p53 accumulation and MIB1
      labelling index has independent prognostic implications in common epithelial
      malignancies of the ovary, irrespective of the disease stage.

PMID- 9233528
TI  - Treatment of men with metastatic non-seminomatous germ cell tumours with cyclical
      POMB/ACE chemotherapy.
AB  - BACKGROUND: An alternating combination chemotherapy schedule for advanced
      nonseminomatous germ cell tumours (NSGCT) has been in use since 1977. PATIENTS
      AND METHODS: Three hundred thirty-nine men with metastatic NSGCT were treated
      with POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D,
      cyclophosphamide and etoposide), including 42 who had received previous
      chemotherapy or radiotherapy. Previously untreated patients were classified
      according to the International Germ Cell Cancer Collaborative Group (IGCCCG)
      model, and 31% were in the worst prognostic group. RESULTS: The median follow-up
      is eight years. The overall survival at five years is 82% (95% confidence
      interval (CI); 78%-85%). The survival of untreated patients exceeded that for
      previously treated patients (log-rank P = 0.04) and of testicular tumours
      exceeded that for primary extragonadal tumours (log-rank P < 0.0001). The
      survival of men with IGCCCG poor prognosis disease at three years is 75% (95% CI:
      65%-84%) compared to 50% in the large cohort which was used to derive the model.
      There were five early treatment related deaths. In addition, five patients
      developed acute leukaemia, one developed a second primary lung adenocarcinoma,
      one man died of pulmonary fibrosis and three men died of cerebrovascular or
      cardiovascular disease. CONCLUSIONS: The POMB/ACE schedule has been employed in a
      large series of men with metastatic NSGCT over two decades. The fatal toxicity is
      equivalent to that described for simpler regimens. It yields equivalent response
      rates and survival in men with good prognosis disease and appears to achieve
      better survival in patients with poor prognosis disease.

PMID- 9233529
TI  - Phase I study of paclitaxel and oral etoposide in previously untreated non-small
      cell and extensive small-cell lung cancer.
AB  - PURPOSE: This phase I study of paclitaxel and oral etoposide was performed to
      determine the safety of the combination in patients with advanced lung cancer who
      had received no prior chemotherapy, and to identify a dose for phase II testing.
      PATIENTS AND METHODS: Patients with locally advanced or metastatic non-small-cell
      lung cancer (NSCLC) or extensive small-cell lung cancer (SCLC), who had received
      no prior chemotherapy were treated with intravenous paclitaxel given as a three
      hour infusion (starting dose 100 mg/m2) and oral etoposide, 100 mg daily for five
      days. Two schedules of administration were used with the paclitaxel given on day
      1 (schedule A) or day 5 (schedule B) of a 21 day cycle. RESULTS: Forty-nine
      patients were entered on the study, four of whom had SCLC. All patients were
      evaluable for toxicity. The maximum tolerated dose was paclitaxel 200 mg/m2 on
      day 1, in combination with oral etoposide 100 mg daily on days 1 to 5 (schedule
      A). The dose limiting toxicities were mucositis, myalgia, diarrhoea, and
      paraesthesiae. Using schedule B, myelosuppression, with febrile neutropenia was
      dose limiting at a paclitaxel dose of 160 mg/m2. Amongst the 45 patients with
      NSCLC there were three complete and eight partial responses (24%; 95% CI 13%
      40%), while there was one complete response in the four patients with SCLC.
      CONCLUSION: Paclitaxel 200 mg/m2 on day 1, with oral etoposide 100 mg daily on
      days 1 to 5 can be administered safely, and is the recommended dose for phase II
      studies.

PMID- 9233530
TI  - Diagnosis of HIV-related primary central nervous system lymphoma: is there still
      a role for brain biopsy? A case history.

PMID- 9233531
TI  - Initial chemotherapy for primary resectable large-cell lymphoma of the stomach.
AB  - BACKGROUND: We aimed to evaluate the safety and effectiveness of a conservative
      approach with short-term chemotherapy with or without consolidation radiotherapy
      in primary resectable large-cell gastric lymphoma in patients not requiring
      emergency surgery at presentation. PATIENTS AND METHODS: Seventeen consecutive
      patients presenting with resectable primary large-cell lymphoma of the stomach
      not requiring immediate surgery were initially treated with chemotherapy with or
      without consolidation radiotherapy. Subtotal or total resection of the stomach
      was planned only as salvage treatment for those patients who failed locally, or
      as emergency surgery in instances of acute iatrogenic complications of treatment.
      Chemotherapy included four to six cycles of an anthracycline-containing regimen,
      and consolidation radiotherapy was planned on the entire stomach and surrounding
      lymph node areas for complete responders readily capable of compliance with a
      daily treatment schedule at our Institution. RESULTS: None of the patients in the
      present series experienced acute iatrogenic morbidity or mortality from local
      complications. After a median follow-up of almost six years, two patients failing
      first-line chemotherapy have died of progressive lymphoma, while 15 patients are
      well and currently disease-free. CONCLUSIONS: Up-front chemotherapy as initial
      treatment for primary gastric large-cell lymphoma appears to be a safe and
      effective treatment by which most patients can probably be spared surgical
      gastrectomy. Consolidation radiation therapy on the stomach can probably improve
      on the effectiveness of chemotherapy alone. More experience is needed to
      elucidate the prognostic factors, treatment-related long-term toxic effects and
      the feasibility of such a treatment administered outside of highly specialized
      institutions.

PMID- 9233532
TI  - A phase II study of raltitrexed ('Tomudex') in patients with hepatocellular
      carcinoma.

PMID- 9233533
TI  - Small-cell carcinoma of the seminal vesicle responding to chemotherapy.

PMID- 9233534
TI  - Is acute dyspnoea a rare side effect of vinorelbine?

PMID- 9233535
TI  - The eastern and western branches of the Wood/Ljungdahl pathway: how the east and
      west were won.

PMID- 9233536
TI  - Acetogenic bacteria: what are the in situ consequences of their diverse metabolic
      versatilities?
AB  - The four decades of the now classic studies by Harland G. Wood and Lars G.
      Ljungdahl lead to the resolution of the autotrophic acetyl-CoA 'Wood/Ljungdahl'
      pathway of acetogenesis. This pathway is the hallmark of acetogens, but is also
      used by other bacteria, including methanogens and sulfate-reducing bacteria, for
      both catabolic and anabolic purposes. Thus, the pathway is wide spread in nature
      and plays an important role in the global turnover of carbon. Because most
      historical studies with acetogens focused on the biochemistry of the acetyl-CoA
      pathway, the metabolic diversity and ecology of acetogens remained largely
      unexplored for many years. Although acetogens were initially conceived to be a
      somewhat obscure bacteriological group with limited metabolic capabilities, it is
      now clear that acctogens are arguably the most metabolically diverse group of
      obligate anaerobes characterized to date. Their anaerobic metabolic arsenal
      includes the capacity to oxidize diverse substrates, including aromatic, C1, C2,
      and halogenated compounds, and engage a large number of alternative energy
      conserving, terminal electron-accepting processes, including classic
      fermentations and the dissimilation of inorganic nitrogen. In this regard, one
      might consider acetogens on a collective basis as the pseudomonads of obligate
      anaerobes. By virtue of their diverse metabolic talents, acetogens can be found
      in essentially all habitats. This review evaluates the metabolic versatilities of
      acetogens relative to both the engagement (regulation) of the acetyl-CoA pathway
      and the ecological roles likely played by this bacteriogical group.

PMID- 9233537
TI  - Enzymology of the fermentation of acetate to methane by Methanosarcina
      thermophila.
AB  - Biologically-produced CH4 derives from either the reduction of CO2 or the methyl
      group of acetate by two separate pathways present in anaerobic mierobes from the
      Archaea domain. Elucidation of the pathway for CO2 reduction to CH4, the first to
      be investigated, has yielded several novel enzymes and cofactors. Most of the CH4
      produced in nature derives from the methyl group of acetate. Methanosarcina
      thermophila is a moderate thermophile which ferments acetate by reducing the
      methyl group to CH4 with electrons derived from oxidation of the carbonyl group
      to CO2. The pathway in M. thermophila is now understood on a biochemical and
      genetic level comparable to understanding of the CO2-reducing pathway. Enzymes
      have been purified and characterized. The genes encoding these enzymes have been
      cloned, sequenced, transcriptionally mapped, and their regulation defined on a
      molecular level. This review emphasizes recent developments concerning the
      enzymes which are unique to the acetate fermentation pathway in M. thermophila.

PMID- 9233538
TI  - Development of genetic approaches for the methane-producing archaebacterium
      Methanococcus maripaludis.
AB  - Methanococcus maripaludis is a strict anaerobe that utilizes H2 or formate as an
      electron donor for CO2 reduction to methane. Recent progress in development of
      genetic systems in this archaebacterium makes it an excellent model system for
      molecular and biochemical studies. This progress includes development of methods
      for growth on solid medium, enriching auxotrophic mutants, efficient
      transformation, and random insertional inactivation of genes. Genetic markers for
      both puromycin and neomycin resistance are available. Lastly, a shuttle vector
      has been constructed from a cryptic methanococcal plasmid. These technical
      advances made it possible to utilize genetic approaches for the study of
      autotrophic CO2 assimilation in methanococci.

PMID- 9233539
TI  - Microbial and plant metabolism of NO.
AB  - During microbial denitrification, NO is produced by reduction of nitrite by
      either the reduced high spin d1 hemes in a unique reductase (NIR) or at the
      expense of a blue copper protein that transfers electrons that move first to a
      type I copper and then to a type II copper in a unique trimeric NIR. This latter
      type of NIR is also produced by several denitrifying filamentous fungi. Reduction
      of NO is then carried out by either a specific cytochrome be complex NOR in
      denitrifying bacteria or a unique cytochrome P-450 in denitrifying filamentous
      fungi. NO is also produced by an anomalous reaction of a molybdoprotein, nitrate
      reductase (NAR), acting on an odd substrate, NO2-. NO is also reduced by a
      multiheme NIR that serves physiologically for reduction of NO2- to NH3. This type
      NIR reduces NO to either N2O, if only partially reduced, or NH3, if fully
      reduced, when it encounters NO. This multiheme NIR is very sensitive to cyanide.
      Transcription of the genes for NIR and NOR production in a denitrifier is
      activated by NO, a process that also requires the presence of the gene product, a
      transcriptional activator, NnrR.

PMID- 9233540
TI  - The acute effects of corticosteroids on cognition: integration of animal and
      human model studies.
AB  - Cognitive deficits following acute administration of corticosteroids have been
      described in experimental animals and humans. In both populations, an inverted-U
      shape relationship has been reported between the dose of corticosteroids
      administered and the nature and extent of the cognitive deficits induced by
      corticosteroids. Further studies in animals have revealed a two-level recognition
      system for adrenal steroids, which was later more clearly resolved into two
      receptor types: Type I and Type II adrenal steroid receptors. The demonstration
      of an inverted-U shape relationship between corticosteroids and cognitive process
      leads to the question as to whether this relationship is generated via the two
      receptor types, exerting effects either via competing or opposing processes or
      via a more synergistic interaction. In this article, we review the effects of
      corticosteroids on animal and human cognition and propose a theoretical framework
      that leads to testable predictions regarding the acute effects of corticosteroids
      on cognitive function. We also discuss some methodological and experimental
      factors that might explain some discrepancies in data obtained from animals and
      humans. Furthermore, we suggest new experimental protocols for use in humans,
      based on animal literature, that could help resolve these discrepancies and
      assess more clearly the nature of the cognitive deficits induced by acute
      administration of corticosteroids.

PMID- 9233541
TI  - Receptor localization in the mammalian dorsal horn and primary afferent neurons.
AB  - The dorsal horn of the spinal cord is a primary receiving area for somatosensory
      input and contains high concentrations of a large variety of receptors. These
      receptors tend to congregate in lamina II, which is a major receiving center for
      fine, presumably nociceptive, somatosensory input. There are rapid
      reorganizations of many of these receptors in response to various stimuli or
      pathological situations. These receptor localizations in the normal and their
      changes after various pertubations modify present concepts about the wiring
      diagram of the nervous system. Accordingly, the present work reviews the receptor
      localizations and relates them to classic organizational patterns in the
      mammalian dorsal horn.

PMID- 9233542
TI  - Is the pial microvessel a good model for blood-brain barrier studies?
AB  - Pial microvessels have commonly been used as model systems for studying blood
      brain barrier (BBB) properties instead of cerebral cortical microvessels. Since
      pial microvessels are relatively accessible they have been especially employed in
      electrophysiological and pharmacological studies. Measurements of electrical
      resistance across endothelial cells (EC) as a measure of their barrier properties
      have been made exclusively from pial microvessels in in vivo BBB studies.
      Similarly the observed responses of microvessels to the application of
      pharmacological agents have commonly been made on pial microvessels as
      representative of BBB vasculature. In this review the properties of pial and
      cerebral microvessels are compared to determine whether the use of the pial
      microvessel as a model for BBB studies is valid. Similarities are described in
      their ultrastructural features, permeability to electron dense tracers and
      molecular characteristics. Measurements of electrical resistance from pial
      microvessels are compared with measurements from cerebral EC monolayers in tissue
      culture and indirect determinations for cerebral microvessels in situ. Two
      notable differences between pial and cerebral microvessels are described in the
      adult nervous system. Tight junctions between cerebral EC appear to consist of a
      uniform population. In pial microvessels however tight junctions consist of two
      populations in one the inter-EC tight junctions resemble those between cerebral
      EC, with fusion of adjacent EC membranes. In the second population the inter-EC
      tight junctions differ with a discernible gap between adjacent EC membranes. The
      distribution of the endothelial barrier antigen (EBA) is uniform between EC of
      cerebral microvessels. By contrast EC of pial microvessels from a heterogeneous
      population for EBA expression which is related to the proximity of the EC to the
      astrocytic glia limitans. The role of astrocytes in the induction and maintenance
      of the BBB characteristics is briefly reviewed. The possible significance of the
      lack of an astrocytic ensheathment of pial microvessels is assessed. In summary,
      caution is urged in employing pial microvessels in BBB studies and the need for
      more information on possible pial microvessel heterogeneity is stressed.

PMID- 9233543
TI  - Roles of platelet-derived growth factor in the developing and mature nervous
      systems.
AB  - In spite of its association by history and name to platelets, platelet-derived
      growth factor (PDGF) exerts important actions in a myriad of tissues, including
      the nervous system. PDGF and PDGF receptors are widely expressed in neuronal and
      glial cells of many regions of both the central and peripheral nervous systems.
      In this topical review, the roles played by PDGF in the development and
      maintenance of the nervous system are discussed. We also discuss the modulatory
      effects of PDGF on synaptic transmission, its role in neoplastic and non
      neoplastic conditions of the central nervous system, and the neuroprotective
      effects of this growth factor.

PMID- 9233544
TI  - Regulation of urea synthesis by diet protein and carbohydrate in normal man and
      in patients with cirrhosis. Relationship to glucagon and insulin.
AB  - Diet protein increases whereas carbohydrates decrease urea synthesis.
      Traditionally, these effects have been explained by changes in substrate supply.
      Diet protein intake increases whereas carbohydrate decreases blood amino acid
      concentration. However, glucose also decreases urea synthesis by a hepatic
      mechanism independent of the decrease in blood amino acid concentration. Whether
      this is due to an effect of glucose in itself, or whether the fall in glucagon or
      the rise in insulin is responsible, was not known. This survey deals with the
      effect of an increase in diet protein intake and of the separate effects of
      glucose, glucagon and insulin on functional hepatic nitrogen clearance in normal
      man and in patients with cirrhosis of the liver. The functional hepatic nitrogen
      clearance is calculated as the slope of the linear regression analysis of alanine
      stimulated urea synthesis rate and blood alpha-amino nitrogen concentration, and
      expresses urea synthesis independent of changes in blood amino acid
      concentration. In patients with cirrhosis, hepatic nitrogen clearance is reduced
      in parallel with liver cell mass, despite high glucagon concentration that would
      normally up-regulate the process. In both healthy subjects and in patients with
      cirrhosis, an increase in diet protein intake (plus approximately 50 g/day) for
      14 days increases hepatic nitrogen clearance by 40%. Thus, in addition to the
      substrate effect, protein intake increases urea synthesis by an effect in the
      liver, probably by enzyme formation. What induces this is not clear but high
      postprandial levels of glucagon may be involved. Although the effect is
      qualitatively intact in the patients, the response relative to the increase in
      protein intake is reduced by two-thirds. The effect may be important to control
      blood amino acid concentration during a high protein diet and may partly explain
      why patients with cirrhosis usually tolerates protein hyperalimentation without
      developing hepatic encephalopathy. It is shown that the reduction of hepatic
      nitrogen clearance by glucose depends on hyperglycaemia, and is accomplished by
      the additive effects of a direct hormone-independent action of glucose, and
      indirectly via suppression of glucagon. Insulin is not a direct controller of
      hepatic nitrogen clearance, but is still considered an important regulator of
      urea synthesis by its reducing effects on blood amino acid concentration. High
      experimental glucagon levels overrule the normal suppressive effect of glucose.
      In contrast, it is shown that the sugar-alcohol xylitol normalises the glucagon
      induced increase in hepatic nitrogen clearance. During normal glucagon levels
      xylitol exerts only a very little decrease in hepatic nitrogen clearance. In
      patients with cirrhosis, glucose does not down-regulate hepatic nitrogen
      clearance. However, when the spontaneous high glucagon levels are normalised by
      somatostatin, glucose decreases hepatic nitrogen clearance. This shows that the
      direct hormone-independent effect of glucose is intact. These findings indicate
      that the high glucagon levels during spontaneous hormone responses overrule the
      suppressive effect of glucose. Incomplete glucose suppression of glucagon
      secretion during alanine infusion contributes to the high glucagon levels. The
      removal of the high glucagon levels decreases hepatic nitrogen clearance in
      itself. Thus, the hyperglucagonaemia may be a compensatory mechanism by which the
      cirrhotic liver to some extent reestablishes its capacity to produce urea. The
      consequence is the defective down-regulation of hepatic nitrogen clearance by
      glucose. The reduction in urea synthesis by glucose, i.e. its nitrogen sparing
      effect, is accomplished by two different mechanisms: A hepatic component
      (reduction of the hepatic nitrogen clearance) and a peripheral component (reduced
      substrate availability mediated by the insulin response). This is an extension of
      former thoughts according to which glucose reduces urea synthesis due solely to

PMID- 9233546
TI  - Biological activity of hormones in preovulatory follicular fluid and serum of
      women undergoing ovarian stimulation.

PMID- 9233545
TI  - Aspects of exposure to UVA tanning sources. Carcinogenic effect in mice and
      melanogenic effect in man and mice.

PMID- 9233547
TI  - Beta-endorphin in cerebrospinal fluid: relation to nociception.

PMID- 9233548
TI  - Crohn's disease--occurrence, course and prognosis. An epidemiologic cohort-study.

PMID- 9233549
TI  - The clinical usefulness of glucated haemoglobin in diabetes care evaluated by use
      of a medical technology assessment strategy.
AB  - With the introduction of measurements of glycated haemoglobin in a single blood
      sample as an index of long-term blood glucose control, the clinically usefulness
      of these measurements was questioned. The aim of this study was to evaluate
      measurements of glycated haemoglobin as a new test for metabolic regulation in
      diabetes management by use of a medical technology assessment strategy.
      Technology assessment in medicine has been defined as "the art and science of
      evaluating medical practices", but the strategy has to be adjusted to the medical
      technology in question always including the following three stages: (a) problem
      definition and identification of medical technology, (b) analysis by testing the
      technology with consideration to its benefit and harm, its costs, and its social
      consequences, and (c) synthesis of the accumulated knowledge about the
      technology. Based on the out-put from the problem definition we found it
      necessary to investigate some of the identified problems ourselves before
      implementation of routine measurements of glycated haemoglobin. Several studies
      were accomplished to validate the laboratory technology in terms of analytical
      reliability and its clinical usefulness. We wanted to (1) define goals of
      analytical quality of assays of glycated haemoglobin based on clinical goals, (2)
      establish a laboratory method for measurements of glycated haemoglobin fulfilling
      the defined goals, (3) investigate the ability of measurements of glycated
      haemoglobin to characterize impaired glucose tolerance, (4) evaluate the clinical
      usefulness of measurements of glycated haemoglobin in the assessment of metabolic
      regulation in non-insulin-dependent diabetes mellitus (NIDDM), (5) compare
      physicians' assessment of metabolic control in insulin-dependent diabetes
      mellitus (IDDM) with measurements of glycated haemoglobin and determine whether
      knowledge of glycated haemoglobin values would result in improved metabolic
      control, and (6) evaluate the organizational and economical consequences of
      introducing regular measurements of glycated haemoglobin. The analysis required a
      multi-disciplinary approach. Based on our own studies and the available data
      information we found that measurements of glycated haemoglobin should be regarded
      the most clinically appropriate test of long-term glycemia and should be
      introduced into routine management of adult patients with IDDM and NIDDM with the
      following guidelines concerning methodologies, clinical utility, organizational
      consequences. The individual laboratory has to establish and secure its own
      method since at present we are still without an internationally accepted
      reference method or reference material. The method should measure HbA1c without
      measuring the labile intermediate pre-HbA1c and provide separate detection of
      haemoglobin variants. We investigated the analytical goals for the performance
      characteristics of assays based on biological variation and on the clinical
      significance of a certain change in concentrations in the individual. Different
      strategies lead to different analytical goals of CVA between 2-4%. An oral
      glucose tolerance test is still required to establish the diagnosis of diabetes.
      Measurements of glycated haemoglobin have been suggested as an alternative but a
      considerable overlap between the WHO-defined groups of normal and impaired
      glucose tolerance was observed. In patients with IDDM our studies demonstrated
      the limitations of traditional clinical judgement and the laboratory procedures
      in providing an accurate assessment of blood glucose control and that knowledge
      of HbA1c values allowed the clinician to identify patients in poor glycemic
      control and lead to improvement in glycemic control. In patients with NIDDM our
      study showed that measurements of HbA1c provided information that was otherwise
      not obtainable in the usual clinical setting in primary health care. Measurements
      of glycated haemoglobin were easily accepted by patients with diabetes. (ABSTRACT
      TRUNCA

PMID- 9233550
TI  - Demographic differences in notifiable infectious disease morbidity--United
      States, 1992-1994.
AB  - Before the 1990s, National Notifiable Diseases Surveillance System (NNDSS) data
      consisted primarily of summary records that lacked demographic information for
      persons with reported diseases. By 1990, all 50 states were using CDC's National
      Electronic Telecommunications System for Surveillance (NETSS) to report
      individual case data that included demographic information (without personal
      identifiers) about most nationally notifiable diseases. These data are important
      for evaluating sex- specific differences in the occurrence of infectious
      diseases; monitoring infectious disease morbidity trends; determining the
      relative disease burdens among demographically diverse subpopulations in the
      United States; targeting prevention; and identifying priorities for research and
      control. This report describes and compares the numbers and rates of cases for
      the most frequently reported nationally notifiable infectious diseases, by sex
      and age of persons with reported illness, reported to CDC during 1992-1994. The
      findings indicate that for seven of the 10 most commonly reported notifiable
      diseases, the reported incidence is lower among women.

PMID- 9233551
TI  - Prolonged poliovirus excretion in an immunodeficient person with vaccine
      associated paralytic poliomyelitis.
AB  - Recently completed molecular studies of poliovirus isolates suggest that viral
      replication of vaccine-related polioviruses may have persisted for as long as 7
      years in a patient with vaccine-associated paralytic poliomyelitis (VAPP) in whom
      common variable immunodeficiency syndrome (CVID) previously had been diagnosed.
      This report summarizes the clinical and virologic data and discusses the possible
      implications of these new findings for the global polio eradication initiative,
      which include how and when to discontinue vaccination when polio has been
      eradicated.

PMID- 9233552
TI  - Adult blood lead epidemiology and surveillance -- United States, first quarter
      1997, and annual 1996.
AB  - CDC's National Institute for Occupational Safety and Health Adult Blood Lead
      Epidemiology and Surveillance (ABLES) program monitors laboratory-reported
      elevated blood lead levels (BLLs) among adults in the United States. Data for New
      Mexico, Rhode Island, and Wyoming are included for the first time in this report,
      increasing the number of reporting states to 27 (Illinois discontinued reporting
      at the end of 1996). Twenty-five states reported surveillance data to the ABLES
      program in 1996. This report presents ABLES data for the first quarter of 1997
      compared with the first quarter of 1996 and annual data for 1996 compared with
      1995. The findings from 1995 and 1996 indicate a continuing decrease in the
      annual number of persons reported with elevated BLLs, although the number of
      reports in the first quarter of 1997 were higher than that for the same period in
      1996.

PMID- 9233553
TI  - Characteristics of community report cards--United States, 1996.
AB  - Efforts to improve community health require methods to compile local health data,
      establish local priorities, and monitor health-related activities. Community
      health report cards (i.e., health assessments or health profiles) are central to
      these efforts. In 1995, the UCLA Center for Healthier Children, Families, and
      Communities initiated a 3-year project to enhance community health improvement
      efforts through the design and use of effective community report cards. During
      the first year of the project, the project examined the construction and
      application of report cards. This report summarizes the results of the first
      year, which indicate great diversity in the targets, processes, and formats of
      community report cards.

PMID- 9233554
TI  - Compendium of psittacosis (chlamydiosis) control, 1997. Centers for Disease
      Control and Prevention.
AB  - Infection with Chlamydia psittaci, often referred to as avian chlamydiosis (AC),
      is an important cause of systemic illness in companion birds (i.e., birds kept by
      humans as pets) and poultry. Infection can be transmitted from infected birds to
      humans. In humans, infection caused by C. psittaci is referred to as psittacosis,
      which can result in fatal pneumonia. This compendium provides information on AC
      (also known as psittacosis, ornithosis, and parrot fever) and psittacosis (also
      known as parrot disease, parrot fever, and chlamydiosis) to public health
      officials, veterinarians, physicians, the companion-bird industry, and others
      concerned with control of the disease and protection of public health. These
      recommendations provide effective, standardized disease control procedures for AC
      in companion birds and will be reviewed and revised as necessary.

PMID- 9233555
TI  - Current status of allogeneic transplantation for haemoglobinopathies.

PMID- 9233556
TI  - Recombinant human thrombopoietin (TPO) stimulates erythropoiesis by inhibiting
      erythroid progenitor cell apoptosis.
AB  - Thrombopoietin (TPO) has been reported to stimulate erythropoiesis, but the
      stimulatory mechanism has not been defined. To address this issue, we performed
      serum-free cell-culture experiments with recombinant human TPO and purified human
      progenitor cells. We found that TPO alone was able to stimulate the megakaryocyte
      colony formation in serum-free cultures, but erythroid colonies were never
      observed. Only in the presence of EPO (erythropoietin) +IL-3 was TPO able to
      stimulate a small increase (approximately 25%) in erythroid colony formation.
      Accordingly, we hypothesized that TPO might have an effect on erythroid
      progenitor cell viability, rather than a direct stimulatory effect. To test this
      idea, CD34+ cells were cultured for 7d in serum-free methylcellulose in the
      presence or absence of TPO, after which time KL+ EPO was added to the cultures.
      Cells which were pre-cultured for 7 d in the presence of TPO gave rise to
      approximately 6 times as many burst forming unit-erythroid (BFU-E) colonies as
      cells which were pre-cultured in the absence of TPO. Further, when primitive
      CD34+, Kit+ MNC were cultured for 3-7 d under serum-free conditions in the
      presence or absence of TPO, significantly fewer cells cultured in the presence of
      TPO displayed apoptotic changes when compared to cells cultured in the absence of
      TPO. Taken together, these results suggest that TPO has little direct stimulatory
      effect on erythroid progenitor cells, but might indirectly enhance erythropoiesis
      by preventing very early erythroid progenitor cells from undergoing apoptotic
      cell death.

PMID- 9233557
TI  - Increased apoptotic cells in bone marrow biopsies from patients with aplastic
      anaemia.
AB  - In order to investigate the involvement of apoptosis in the pathogenesis of
      aplastic anaemia (AA) we determined the proportion of apoptotic cells in paraffin
      embedded bone marrow biopsies from patients with aplastic anaemia using an in
      situ TdT-catalysed DNA nick end labelling (TUNEL) staining method. A significant
      increase in the proportion of mononuclear apoptotic cells was demonstrated in
      biopsies from patients with aplastic anaemia (8.19 +/- 1.45%) when compared with
      controls (2.07 +/- 0.86%). These data support the view that apoptosis may play a
      role in the pathophysiology of bone marrow failure.

PMID- 9233558
TI  - Recurrent PIG-A mutation (IVS5+1G-->A) in a paediatric case of paroxysmal
      nocturnal haemoglobinuria: detection by the protein truncation test.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemopoietic stem cell
      disorder caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored
      surface proteins due to a deficient biosynthesis of GPI-anchor. The disease
      occurs predominantly in adults, and very few cases have been described in
      children and adolescents. Recent analyses have shown that null mutations in the X
      linked PIG-A (phosphatidylinositol glycan-class A) gene are responsible for GPI
      anchor deficiency in most PNH adult patients analysed. We report a young male
      from southern France who was diagnosed with PNH at 12 years of age during follow
      up of aplastic anaemia. To further elucidate the molecular basis of PNH occurring
      in childhood, we used the powerful and rapid protein truncation test to scan for
      truncative mutations in the entire PIG-A mRNA reverse transcribed and amplified
      from blood mononuclear cells. The somatic defect responsible for PNH in the
      patient was found to be a splicing mutation. IVS5+1G-->A, which has previously
      been described in two Asiatic adults with PNH.

PMID- 9233559
TI  - Do HbSS erythrocytes lose KCl in physiological conditions?
AB  - KCl cotransporter activity in sickle (HbSS) red blood cells (RBCs) was measured
      in cells suspended in 'simple' physiological saline, saline augmented with
      inorganic salts, and autologous plasma. Our results showed that the transporter
      was only functioning at 20% of the level of cells in saline when cells were
      resuspended in autologous plasma. Kinetic analysis of the data showed that plasma
      decreased both Vmax and Km for K+ of the transporter. The plasma factor(s)
      responsible was heat-stable and dialysable (i.e. size < 10 kD). Adding magnesium,
      calcium, inorganic phosphate or bicarbonate to 'simple' saline to mimic the
      effect of plasma revealed that Mg2+ and Ca2+ had no significant effect at
      physiological concentrations. Pi was not effective at 1.1 mM, but did inhibit
      significantly (42+/-2%) at 5.6 mM. HCO3- had a major inhibitory effect on K+
      influx when added to saline, and was identified as the principal candidate for
      the plasma effect. We suggest bicarbonate may play a significant role in
      modifying KCl cotransport, and hence HbSS cell volume in vivo. It acts by
      altering the set point of the transporter via the signalling systems involved in
      its regulation.

PMID- 9233560
TI  - Heterogenous band 3 deficiency in hereditary spherocytosis related to different
      band 3 gene defects.
AB  - Among 80 hereditary spherocytosis (HS) kindreds studied using denaturing
      electrophoretic separation of solubilized eythrocyte membrane proteins, we
      recognized three prominent subsets: HS with isolated spectrin deficiency, HS with
      combined spectrin and ankyrin deficiency, and HS with band 3 deficiency These
      three subsets represent more than 80% of the HS kindreds studied. In this study,
      eight dominant HS kindreds with band 3 deficiency were investigated for band 3
      mutations. In three of these kindreds, linkage analyses confirmed the band 3 gene
      as the culprit gene. In an attempt to identify the responsible mutations,
      denaturing gradient gel electrophoresis (DGGE) was used to explore the coding
      exons (exons 2-20) of band 3 gene. Five different mutations were found in the
      eight kindreds. In five kindreds we identified substitutions of highly conserved
      residues, positioned at boundaries of putative transmembrane segments: a C --> T
      substitution at codon 490 changed arginine (CGC) to cysteine (TGC) in three
      kindreds, a C --> T substitution at codon 837 changed threonine (ACG) to
      methionine (ATG) in two kindreds. In the sixth kindred a G deletion was found in
      a stretch of five G starting at position 1475, leading to a stop codon either at
      position 1527 or 1565. In the seventh kindred a T deletion at position 1600
      resulted in a stop codon at position 1733 and in the last kindred a T deletion
      was identified at position 355, leading to a stop codon at position 447. The
      mutant transcript was present in HS patients bearing missense mutations, whereas
      only the normal transcript was found in HS patients with frameshift mutations. In
      the latter group the mean decrease in membrane band 3 content was significantly
      lower, leading to speculation that missense mutations may have some sort of
      dominant negative effect.

PMID- 9233561
TI  - Molecular characterization of G6PD deficiency in Southern Italy: heterogeneity,
      correlation genotype-phenotype and description of a new variant (G6PD Neapolis).
AB  - We report on the molecular basis of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency in Southern Italy (Campania region). Thirty-one unrelated G6PD
      deficient males were analysed at DNA level for the presence of G6PD gene
      mutations. Nine different G6PD variants were identified, eight of which have
      already been described (Mediterranean, Seattle, two different A-, Santamaria,
      Cassano, Union and Cosenza). G6PD Mediterranean, Santamaria, A- and Union were
      associated with haemolytic episodes. G6PD Seattle, which is polymorphic in
      several populations, Cassano and Cosenza appeared to be asymptomatic. A new
      variant (G6PD Neapolis) is reported here. The 467(Pro-->Arg) substitution
      responsible for G6PD Neapolis is discussed in the light of the current 3D model
      of human G6PD and in comparison with other natural mutations which occur in the
      proximity of residue 467.

PMID- 9233562
TI  - First description of a frameshift mutation in the alpha1-globin gene associated
      with alpha-thalassaemia.
AB  - A frameshift mutation in the alpha1-globin gene, responsible for a clinically
      mild alpha-thalassaemia phenotype, has been characterized in a Spanish woman.
      After excluding the most common forms of alpha-thalassaemia found in the
      Mediterranean area, both alpha-globin genes (alpha1 and alpha2) were amplified
      and analysed selectively by non-radioactive single-strand conformation
      polymorphism (SSCP). An abnormal SSCP mobility was present in the second exon of
      the alpha1-globin gene and direct sequence analysis revealed a 13 bp deletion
      (between codons 51 and 55) affecting a single allele. The consequence of this
      mutation is a reading frameshift leading to a novel amino acid coding sequence
      from codons 51-61 and a premature stop signal at new position 62, which results
      in a net reduction of the affected alpha-globin chain output. The presence of
      this new mutation was confirmed by restriction enzyme analysis of the specific
      PCR product.

PMID- 9233563
TI  - In-vivo platelet activation correlates with red cell anionic phospholipid
      exposure in patients with beta-thalassaemia major.
AB  - Several clinical and laboratory findings suggest the presence of a chronic
      hypercoagulable state in patients with beta-thalassaemia major (TM). We have
      previously shown that isolated TM red blood cells (RBC) strongly enhance
      prothrombin activation, suggesting an increased membrane exposure of procoagulant
      phospholipids (i.e. phosphatidylserine). In this study we quantitated the
      procoagulant activity of RBC in TM and thalassaemia intermedia (TI) patients. We
      also determined the fraction of activated platelets expressing p-selectin (CD62p)
      or CD63 in these subjects. Both assays were performed by dual-colour flow
      cytometry. A significantly (P < 0.01) higher fraction of FITC-annexin V-labelled
      RBC was found in TM and TI patients, compared to the controls. A highly
      significant correlation (P < 0.001) was found in TM patients between the number
      of RBC-bound annexin V molecules and the fraction of CD62p (p-selectin) or CD63
      positive platelets. This association between annexin V binding to TM RBC and the
      expression of platelet activation markers was also found in individual TM
      patients over time. Thus, the procoagulant surface of TM RBC may accelerate
      thrombin generation in vivo which, in turn, triggers platelet activation.

PMID- 9233564
TI  - Bernard-Soulier syndrome Karlstad: Trp 498-->Stop mutation resulting in a
      truncated glycoprotein Ib alpha that contains part of the transmembranous domain.
AB  - In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are
      deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von
      Willebrand factor. The components of the complex are encoded by separate genes.
      Patients with this syndrome have a variable expression level of the receptor
      protein on platelets depending on the specific genetic abnormality. We describe a
      patient with life-long bleeding symptoms, who is homozygous for a unique stop
      mutation. Trp 498-->Stop in the GPIb alpha gene, resulting in a truncated GPIb
      alpha polypeptide chain. In contrast to previously reported truncated forms of
      GPIb alpha, this form contains a portion of the transmembranous domain as well as
      the juxtamembranous cysteines engaged in a disulphide bond with GPIb beta. Flow
      cytometry with GPIb alpha antibodies demonstrated the presence of GPIb on the
      patient's platelets, although in reduced amounts compared to normal controls.
      GPIX was similarly detectable. Immunoblotting demonstrated that the patient
      synthesized a truncated GPIb alpha of the expected size of 130 K, which was,
      however, sensitive to proteolysis. These studies show that GPIb alpha lacking the
      intracytoplasmic tail can be expressed at the platelet surface provided elements
      of the transmembranous domain are present.

PMID- 9233565
TI  - Immunoglobulins targeting both GPIIb/IIIa and GPIb/IX in chronic idiopathic
      thrombocytopenic purpura (ITP): evidence for at least two different IgG
      antibodies.
AB  - Antiplatelet antibodies in chronic idiopathic thrombocytopenic purpura (ITP)
      mainly target glycoprotein (GP) IIb/IIIa and GPIb/IX. Previous studies, employing
      modern antigen-specific assays, indicate that serum reactive with both GPIIb/IIIa
      and GPIb/IX is not an uncommon finding in chronic ITP. However, the mechanism
      behind this dual reactivity remains unclear. We studied sera from 72 patients
      with chronic ITP using modified GPIIb/IIIa- and GPIb/IX-specific MAIPA assays.
      Among the 34 positive sera, seven showed strong reactivity against both
      GPIIb/IIIa and GPIb/IX. These seven dual reactive ITP sera were further analysed
      by absorption studies. It was found that sera absorbed with immobilized GPIb/IX
      lost nearly all serum IgG specific for GPIb/IX but fully retained the IgG
      specific for GPIIb/IIIa. Conversely, sera absorbed with immobilized GPIIb/IIIa
      retained their reactivity only with GPIb/IX. These findings demonstrate that ITP
      sera, reactive with both GPIIb/IIIa and GPIb/IX, contain at least two different
      IgG antibody populations, each reactive with only one of the GP complexes.

PMID- 9233566
TI  - Novel and diagnostically applicable information from optical waveform analysis of
      blood coagulation in disseminated intravascular coagulation.
AB  - Transmittance waveform is the term applied to the optical profile generated from
      the process of clot formation on standard coagulation tests run on the MDA-180, a
      new-generation automated coagulation analyser. In patients with disseminated
      intravascular coagulation, a characteristically abnormal 'biphasic change' is
      seen on both the activated partial thromboplastin time and thrombin time
      waveforms. Increasing steepness of the initial slope on the waveform correlates
      with clinical deterioration and fulminant progression. Although the mechanism
      underlying the biphasic appearance remains to be elucidated, its identification
      provides the diagnostic laboratory with a simple, rapid and robust assay for
      disseminated intravascular coagulation that can help the clinician with urgent
      and appropriate therapeutic interventions.

PMID- 9233567
TI  - International Normalized Ratio determination using calibrated reference plasmas.
AB  - We have compared the conventional method of International Normalized Ratio (INR)
      determination with an alternative method involving extrapolation from a
      calibration curve using freeze-dried 'reference' plasmas. The latter approach
      does not require the determination of a mean normal prothrombin time (MNPT) or
      local system International Sensitivity Index (ISI). Calibration curves were
      constructed by plotting local prothrombin time (PT) against assigned INR values
      for a normal plasma and either two plasma pools from patients on oral
      anticoagulants or two artificially depleted plasmas. Six laboratories determined
      the INR of a freeze-dried test plasma and frozen patient plasma samples using the
      conventional method and by extrapolation. Similarities in the results with the
      freeze-dried test plasma and the frozen plasmas were encouraging for the
      projected use with fresh plasma samples. INR values by the conventional method
      for the test plasma gave an overall mean of 2.73 and inter-laboratory variability
      (gcv%) of 8.92%, whereas estimates by extrapolation against the normal and
      patient plasmas or the normal and artificially depleted plasmas gave identical
      overall mean INR values of 2.70 with inter-laboratory variability (gcv%) of 3.44%
      and 4.92% respectively. The results indicate that INR determination by
      extrapolation is associated with reduced interlaboratory variability.

PMID- 9233568
TI  - Further evidence for the importance of an androgen response element in the factor
      IX promoter.
AB  - Previous work involving the characterizing of a factor IX promoter mutation (-26
      G-->C) of a 21-year-old patient with severe haemophilia B suggested that an
      androgen response element (ARE) was present in the wild-type factor IX promoter
      but was disrupted in this patient. However, other theories not involving this ARE
      have been suggested for the mechanism of recovery in the more typical (Leyden)
      promoter patients, so that the ARE hypothesis requires further evidence if it is
      to be accepted. We now present a case history and functional data on another 48
      year-old severe haemophilia B patient (UK232) with a different (G-->A) mutation
      at the same position, -26. This mutation impairs transactivation of the minimal
      factor IX promoter region (-220-->+43) by HNF4 in transient transfection
      experiments in HepG2 and HeLa cells. It disrupts binding of both androgen
      receptor (AR) and HNF4 to oligonucleotides spanning this region (-40-->-9) in
      competition gel mobility shift assays. It impairs AR/testosterone transactivation
      of these oligonucleotides (-40-->-9) when tetramerized upstream of a CAT reporter
      gene in cotransfection assays in HeLa cells. And, finally, no clinical recovery
      has occurred since puberty. These results strengthen the evidence for the
      importance of nucleotide -26, both for the normal transcription of the gene in
      response to HNF4 and for the proposed Leyden recovery mechanism in response to AR
      and testosterone acting directly through the factor IX ARE.

PMID- 9233569
TI  - Activation during preparation of therapeutic platelets affects deterioration
      during storage: a comparative flow cytometric study of different production
      methods.
AB  - Three different separation methods, all using centrifugation, are routinely used
      to prepare therapeutic platelet concentrates from human donor blood. Platelet
      concentrates derived from platelet-rich plasma (PRP-PC), buffy coat (BC-PC) and
      apheresis (AP-PC) were investigated at the end of production, and over an 8 d
      storage period. Change in platelet surface markers were measured by flow
      cytometry, using fluorescein-conjugated antibodies to fibrinogen, P-selectin
      (CD62P), GPIIb-IIIa (CD41), GPIb alpha (CD42b) and GPV (CD42d), and fluorescein
      conjugated Annexin V was used to measure expression of anionic phospholipid. All
      concentrates showed some changes during preparation but PRP-PC underwent the
      greatest changes with significantly higher levels of P-selectin (P<0.001) and
      bound Annexin V (P=0.001) than AP-PC or BC-PC, and lower levels of GPIb alpha
      (P=0.002) and GPV (P<0.001). These changes were attributable to component
      separation rather than venesection. These markers all continued to change on
      storage with a strong positive correlation between the changes seen during
      production and those after 5 d storage. PRP-PC continued to show the greatest
      changes whereas BC-PC showed the least. Fibrinogen was bound to 40-50% of
      platelets in all preparations and this did not alter significantly on storage
      whereas total expression of GPIIb-IIIa remained unchanged throughout. There was
      no evidence that the platelet surface changes were thrombin-mediated and
      leucocyte depletion of BP-PC by filtration had no effect on the changes. It is
      proposed that the deterioration of platelet concentrates during storage may be
      related to activation occurring during preparation. 'Whole blood' flow cytometry
      using a panel of fluorescein-labelled reagents provides an informative method for
      evaluating platelet concentrates.

PMID- 9233570
TI  - Cytogenetic abnormalities and their prognostic significance in idiopathic
      myelofibrosis: a study of 106 cases.
AB  - The prognostic significance of cytogenetic abnormalities was determined in 106
      patients with well-characterized idiopathic myelofibrosis who were successfully
      karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality
      (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic
      defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy
      1q (seven cases), were present in 64.8% (24/37) of patients with clonal
      abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal
      karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional
      clinical and haematological parameters recorded at diagnosis, age (P<0.01),
      anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l,
      P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated
      with a shorter survival. In contrast, sex, spleen and liver size, and percentage
      blast cells were not found to be significant. Multivariate analysis, using Cox's
      regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte
      counts to retain their unfavourable prognostic significance. A simple and useful
      schema for predicting survival in idiopathic myelofibrosis has been produced by
      combining age, haemoglobin concentration and karyotype with median survival times
      varying from 180 months (good-risk group) to 16 months (poor-risk group).

PMID- 9233571
TI  - Spleen sizing by ultrasound in polycythaemia and thrombocythaemia: comparison
      with SPECT.
AB  - Detection of non-palpable early splenic enlargement may aid diagnosis of primary
      polycythaemia (PP) and primary thrombocythaemia (PT). In this study linear spleen
      sizing by ultrasound has been compared with spleen volume estimation by single
      photon emission computerized tomography (SPECT) in 26 patients. Spleen length by
      ultrasound correlated well with SPECT volume estimation. Ultrasound spleen length
      was also measured in 60 normal control subjects where the upper limit of the 95%
      reference range was 11.6 cm. Changes in spleen length with both age and body
      weight were substantial and overshadowed the imperfect reproducibility of this
      method. Therefore, interpretation of an individual's measured spleen length
      should be in relation to that predicted for adults of the same age and weight,
      particularly at the extremes of the younger, heavier patients and also the older,
      lighter patients. Ultrasound spleen lengths of different patient groups (21 PP,
      26 PT, 17 idiopathic erythrocytosis, 12 secondary polycythaemia, nine apparent
      polycythaemia) were compared both using the measured overall reference range and
      the differences from the values predicted for their age and weight. The
      comparison showed that almost all patients with PP whose spleens were not
      palpable had spleen lengths greater than the upper limit for the normal control
      group, but separation from the other patient groups was incomplete. Detection of
      non-palpable splenomegaly by ultrasound length should remain a 'minor' criterion
      amongst the 'proposed modified diagnostic criteria' of PP.

PMID- 9233572
TI  - Altered surface expression of effector cell molecules on neutrophils in
      myelodysplastic syndromes.
AB  - The surface expression of effector cell molecules on neutrophils was examined in
      18 patients with myelodysplastic syndromes (MDS) and 20 healthy control subjects.
      The MDS patients were further classified as low clinical risk (L-MDS, n=7) and
      high clinical risk (H-MDS, n=11). The expression of Fc receptors for IgG (FcR),
      complement receptors (CR) and cellular adhesion molecules on neutrophils was
      determined by flow cytometry and monoclonal antibodies. The effect of granulocyte
      colony-stimulating factor (G-CSF) and tumour necrosis factor-alpha (TNF) on L
      selectin shedding and CR up-regulation on neutrophils was also examined. The
      percentage of FcRI-positive neutrophils and CD11b/CR3 expression on neutrophils
      were significantly increased in the H-MDS patients when compared to the controls.
      In contrast, the expression of FcRII, FcRIII, L-selectin, LFA-1 and CD18 on
      neutrophils was significantly reduced in the H-MDS patients compared with the
      controls. The L-MDS neutrophils exhibited lower expressions of CR1, L-selectin,
      LFA-1 and CD18 than those of the controls. Neutrophils from some H-MDS patients
      showed impaired L-selectin shedding and CR up-regulation after stimulation with G
      CSF or TNF, although these were not significantly different when assessed in the
      whole H-MDS group. These findings suggest that an altered surface expression of
      effector cell molecules and an impaired modulation of cellular adhesion molecules
      on neutrophils may contribute to the increased susceptibility to bacterial
      infections in MDS patients.

PMID- 9233573
TI  - Immunoglobulin class switch from IgA1 to IgG2 and simultaneous association with
      Bence Jones proteinuria in the escape phase in a myeloma patient treated with
      interferon alpha.
AB  - Immunoglobulin (Ig) class switch from alpha1 to gamma2 associated with kappa-type
      Bence Jones proteinuria was evident in the escape phase of an IgA1 myeloma
      patient treated with interferon alpha (IFN alpha). The additional M-protein, IgG2
      kappa, level rapidly increased and was associated with Bence Jones proteinuria,
      whereas monoclonal IgA1-kappa progressively declined. The N-terminal 21 amino
      acid sequences of the kappa-chains of monoclonal IgA1, IgG2 and the Bence Jones
      protein were the same. The N-terminal 15 amino acid sequence of the gamma2-chain
      was identical to that of the alpha1-chain. Based on these findings, the IgA1
      myeloma cells underwent a class switch in CH gene expression from alpha1 to
      gamma2 with cell differentiation in vivo. The mechanism of the Ig class switching
      is discussed from three points of view: (1) Increase in immature and
      plasmablastic myeloma cells in the escape phase is susceptible to Ig class
      switching by the T-cell-derived cytokines. (2) We presumed that administered IFN
      alpha increased the amounts of secreted IFN gamma from the Th1 cells. (3) Due to
      a large quantity of IFN gamma, an inducer of Cgamma2 germline transcript, Ig
      class switching occurred stepwise from the alpha1 constant region gene to the
      next 3'CH gamma2 gene.

PMID- 9233574
TI  - Interferon-gamma+ and interleukin-2+ T cells in peripheral blood from multiple
      myeloma patients in relation to disease status and maintenance therapy with
      interferon-alpha2b (intron A).
AB  - Peripheral blood T cells from 83 patients with multiple myeloma (MM) were
      examined for the production of interferon-gamma (INF-gamma) and interleukin-2 (IL
      2) using three-colour flow cytometry. Comparisons were made between the
      percentage of cytokine-positive lymphocytes in normal donors and in patients
      during remission or relapse. Patients were divided into those who were on
      maintenance therapy with interferon-alpha2b (intron A) and those who had no
      further treatment after high-dose melphalan (HDM) with or without autologous bone
      marrow (ABMR) or peripheral blood stem cell rescue (PBSCR). The percentage of INF
      gamma+/CD3+, INF gamma+/CD45RO+/CD3+ and IL-2+/CD8+ was higher in patients on INF
      alpha2b during remission and relapse compared with normal donors (P<0.005).
      During remission INF gamma+/CD45RO+/CD3+ and IL-2+/CD8+ lymphocytes were higher
      in patients not on INF alpha2b (P<0.05 and P<0.005, respectively). In relapsed
      patients INF gamma+/CD3+ and INF gamma+/CD45RO+/CD3+ were increased in patients
      not taking INF alpha2b (P<0.005). There was no significant difference between the
      percentages of cytokine-positive lymphocytes in patients taking or not taking INF
      alpha2b either during remission or relapse. Plasma IL-6 levels were similar in
      both groups of patients during remission. The data suggest that if maintenance
      therapy with INF alpha2b induces the synthesis of INF gamma and IL-2 in vivo, the
      magnitude of the effect is small and may be unimportant in providing an anti
      tumour effect in the majority of patients.

PMID- 9233575
TI  - The effects on growth and survival of IL-6 can be dissociated in the U-266-1970/U
      266-1984 and HL407E/HL407L human multiple myeloma cell lines.
AB  - Several studies have documented IL-6-dependent growth promotion of murine and
      human neoplastic plasma cells. However, it is well known that human multiple
      myeloma (MM) cells in vitro show a considerable degree of heterogeneity
      concerning growth and survival requirements. This heterogeneity, which probably
      reflects overlapping effects of feeder cells, interleukin 6 (IL-6) and components
      of fetal calf serum (FCS) as well as tumour heterogeneity in vivo, has hampered
      the elucidation of molecular mechanisms underlying the effects of IL-6. In an
      attempt to dissociate growth and survival promotion of IL-6, we have studied two
      pairs of human MM cell lines, HL407E/HL407L and U-266-1970/U-266-1984, selected
      to represent different stages of in vitro tumour progression and dependence of
      feeder cells and exogenous IL-6. We demonstrated that exogenous IL-6, in the
      presence of FCS, conveyed: (a) a strong growth stimulatory effect with weak or no
      survival promotion in HL407L and U-266-1970 cells; (b) promotion of survival with
      no effects on growth in HL407E cells; (c) no growth or survival promotion to U
      266-1984. Moreover, our results suggested that IL-6 may enhance apoptosis in U
      266-1970/U-266-1984 cells, and that FCS may interfere with IL-6 in its growth
      stimulatory effect. The relative dissociation of growth, survival and apoptotic
      effects of IL-6 leads to the conclusion that the HL407E/HL407L and U-266-1970/U
      266-1984 pairs of cell lines provide a useful human model system to study
      molecular mechanisms underlying these separate events.

PMID- 9233576
TI  - Microsatellite instability and other molecular abnormalities in childhood acute
      lymphoblastic leukaemia.
AB  - Microsatellite instability (MSI) has been considered to represent the defect of
      DNA mismatch repair systems and has been implicated in the tumourigenesis of
      several human malignancies. To investigate the possible presence of
      microsatellite instability in childhood acute lymphoblastic leukaemia (ALL), we
      examined 48 primary ALL samples. Instability was determined at 85 different
      microsatellite loci localized to 12 different chromosome arms. Microsatellite
      instability was detected in five (10%) samples. Interestingly, the instability
      was found at chromosomal regions associated with frequent alterations. Two
      samples had instability at the microsatellite marker within the TEL gene on
      chromosome arm 12p. Two other samples had instability at a microsatellite marker
      close to CDKN2/p16 on 9p; one of these samples had a homozygous deletion at 9p21.
      The fifth sample had instability at the microsatellite marker on 6q, which we
      have found is a frequent region of loss of heterozygosity in childhood ALL. Taken
      together, instability was rare in childhood ALL, but was localized to the three
      most frequently deleted chromosome regions in childhood ALL, suggesting that
      localized microsatellite instability may identify a fragile chromosomal region
      which could result in alteration of surrounding target genes and lead to
      leukaemia.

PMID- 9233577
TI  - A prospective study of minimal residual disease in childhood B-lineage acute
      lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive
      factor of relapse.
AB  - We prospectively investigated minimal residual disease (MRD) in 51 children with
      B-lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93
      protocol. PCR follow-up was performed in children in morphological and
      cytogenetic complete remission, provided an immunoglobulin (IgH) gene
      rearrangement could be detected using FR 3/J(H) amplimers. MRD was studied
      according to our previously described methodology, with a few modifications
      including the use of a consensus J(H) probe to control for PCR efficiency
      variations. Out of the initial 51 patients, 34 were assessable for MRD at the end
      of induction at the time of analysis. MRD levels were as follows: > 1/10(3) in
      26%, 1/10(3) to 1/10(4) in 50% and < 1/10(4) or not detectable in 24%. With a
      median follow-up of 20 months there were five relapses, all of which occurred in
      the group of patients with MRD > 1/10(3). To date, none of the patients with MRD
      < or = 1/10(3) (good molecular responder) has relapsed. Classification according
      to molecular response at the end of induction did not correlate with the
      conventional risks groups: there were no statistically significant differences
      between good and bad molecular responders. Of particular interest is the absence
      of correlation between WBC at diagnosis and MRD level at the end of induction. We
      conclude that classification of patients into good and bad molecular responders
      using PCR seems to be a better prognostic indicator than conventional risk
      factors in childhood B-lineage ALL. Patients with MRD level > 1/10(3) have a
      particularly poor outcome and should always be considered for alternative
      therapeutic strategies in the future, whereas in good molecular responders
      belonging to poor or intermediate risk categories, treatment de-escalation might
      be contemplated.

PMID- 9233578
TI  - Inverse correlation between loss of heterozygosity of the short arm of chromosome
      12 and p15ink4B/p16ink4 gene inactivation in childhood acute lymphoblastic
      leukaemia.
AB  - Seventy-four patients with acute lymphoblastic leukaemia (ALL) were analysed with
      limited allelotyping to detect loss of heterozygosity on chromosome segments 6q,
      9p, 12p and 13q in order to detect patterns of genetic alteration. In the case of
      chromosome 9, analyses were also performed to detect inactivation of the p15ink4B
      and p16ink4 genes by Southern blot and sequencing techniques. The deletion data
      from these chromosomes were correlated to each other and to clinical features
      including prognosis. Allelic loss of these chromosomal regions could be detected
      in 24% (6q), 15% (12p) and 10% (13q) of the patients respectively, whereas
      aberrations involving 9p were detected in approximately 50% of the cases. There
      was an inverse correlation between loss of heterozygosity (LOH) for chromosome 12
      and inactivation of the p16ink4 gene. This finding may suggest that a
      leukaemogenic event on chromosome 12p affects the same pathway of cell-cycle
      control as p16ink4 inactivation or, alternatively, reflects the fact that these
      mutations tend to occur in cells of different lineages.

PMID- 9233579
TI  - Expression of CD8beta and alteration of cell surface phenotype in adult T-cell
      leukaemia cells.
AB  - Typical adult T-cell leukaemia (ATL) cells have a CD4+ CD8- cell surface
      phenotype, but atypical phenotypes such as CD4+ CD8+ and CD4- CD8+ have also been
      reported. The CD8 molecule is composed of alpha and beta chains and commonly used
      monoclonal antibodies against CD8 molecule detect only CD8alpha. Since it has
      been reported that CD8alpha can be induced in mature CD4+ T cells by cell
      activation, but not CD8beta, we studied whether ATL cells which express CD8alpha
      may also express CD8beta. We found some cases of CD8alpha+ ATL were also positive
      for CD8beta. Furthermore, we experienced a case whose ATL cell surface phenotype
      changed from CD4+ CD8alpha+ CD8beta+ to CD4- CD8alpha+ CD8beta+ and finally to
      CD4+ CD8alpha- CD8beta-. Southern blot analysis revealed that the monoclonal
      integration of human T lymphotropic virus type I (HTLV-I) was identical
      throughout the course of the study, indicating that a single clone had
      demonstrated the alterations. These data suggest that peripheral CD4+ CD8+ ATL
      cells can express not only CD8alpha, but also CD8beta and that a single ATL cell
      clone has the potential to change its surface phenotype in vivo as well as in
      vitro.

PMID- 9233580
TI  - Exon/intron structure of the human AF-4 gene, a member of the AF-4/LAF-4/FMR-2
      gene family coding for a nuclear protein with structural alterations in acute
      leukaemia.
AB  - The AF-4 gene on human chromosome 4q21 is involved in reciprocal translocations
      to the ALL-1 gene on chromosome 11q23, which are associated with acute
      lymphoblastic leukaemias. A set of recombinant phage carrying genomic fragments
      for the coding region and flanking sequences of the AF-4 gene were isolated.
      Phage inserts were assembled into four contigs with 21 exons, and an intron phase
      map was produced enabling the interpretation of translocation-generated fusion
      proteins. The gene contains two alternative first exons, 1a and 1b, both
      including a translation initiation codon. The translocation breakpoint cluster
      region is flanked by exons 3 and 6 and two different polyadenylation signals were
      identified. Polyclonal antisera directed against three different portions of the
      AF-4 protein were produced and used to detect a 116 kD protein in cellular
      extracts of human B-lymphoblastoid and proB cell lines. In mitogen-stimulated
      human peripheral blood mononuclear cells the AF-4 antigen was predominantly
      located in the nucleus. The AF-4 gene is a member of the AF-4, LAF-4 and FMR-2
      gene family. The members of this family encode serine-proline-rich proteins with
      properties of nuclear transcription factors. Comparison of AF-4 protein coding
      sequences with the LAF-4 and FMR-2 sequences revealed five highly conserved
      domains of potential functional relevance.

PMID- 9233582
TI  - Trisomy 14 is a non-random karyotypic abnormality associated with myeloid
      malignancies.
AB  - Isolated gain of chromosome 14 (trisomy 14 or +14) has been reported in myeloid
      malignancy. Seven cases were identified by review of all diagnostic bone marrow
      specimens with cytogenetics performed at our institution from 1983 to 1995.
      Median age was older (72 years) and diagnosis was myelodysplasia in the majority
      of cases. Although trilineage dysplasia occurred, platelet counts were relatively
      well preserved (median 131 x 10(9)/l). Mosaic karyotype (normal plus abnormal
      metaphases) was seen in the majority of cases, and survival from diagnosis was
      short (<2 years). These features are consistent with data from 30 previously
      published cases, and support the hypothesis that trisomy 14 occurs as a non
      random cytogenetic abnormality in association with myeloid malignancy.

PMID- 9233581
TI  - Acute basophilic leukaemia and translocation t(X;6)(p11;q23).
AB  - We report two infants with acute basophilic leukaemia associated with a
      t(X;6)(p11;q23) as the sole abnormality. Morphologic evidence of basophilic
      lineage was provided by light and electron microscopy. Both patients also had a
      similar presentation on diagnosis, characterized by clinical signs consistent
      with a hyperhistaminaemia syndrome, i.e. urticarian rashes and gastro-intestinal
      disorders evocative of peptic ulcer. Immunophenotypes differed in the two
      patients, one expressing CD24, CD13 and CD33, whereas only CD117 was found in the
      other. Basophilic acute leukaemia, a rare group among acute leukaemias, might be
      nonrandomly associated with a specific chromosomal abnormality, t(X;6)(p11;q23).
      This new entity might also be identifiable by an uncommon clinical presentation
      and occurrence in infancy.

PMID- 9233583
TI  - Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce
      differentiation in myelomonocytic leukaemia cells.
AB  - The vitamin D3 derived hormone 1.25 (OH)2 vitamin D3 (1,25 D3) is able to induce
      growth arrest and differentiation in myelomonocytic leukaemia cells. In order to
      allow for specific delivery to leukaemic cells the lipophilic compound was
      incorporated into the lipid membranes of liposomes. Liposomal 1.25 D3 reduced
      proliferation as measured by 3H-thymidine incorporation in HL60 leukaemia cells
      by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3
      65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D3 was
      more potent and had the same activity at 4.8 nM. The effect of the liposomal
      compounds was specific to myeloid cells as they reduced proliferation in
      myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in
      the T-cell lines Jurkat and Molt 4. The antiproliferative effect of liposomal
      1,25 D3 was associated with an induction of differentiation since treated HL60
      cells showed a monocytic morphology, increased expression of CD14 and decreased
      expression of CD33. When peripheral blood leukaemic cells from M4 and M5 acute
      myeloid leukaemia (AML) patients were admixed with liposomal compounds an
      antiproliferative effect was seen in all five cases, including the two cases
      where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2
      vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia.

PMID- 9233584
TI  - Analysis of Tie receptor tyrosine kinase in haemopoietic progenitor and leukaemia
      cells.
AB  - We generated a panel of monoclonal antibodies against the extracellular domain of
      the Tie receptor tyrosine kinase and studied its expression in human haemopoietic
      and tumour cell lines and in samples from leukaemia patients. Most of the
      erythroblastic/megakaryoblastic (6/8), 2/7 myeloid and 3/6 B-lymphoblastic
      leukaemia cell lines were Tie-positive. The erythroblastic/megakaryoblastic
      leukaemia cell lines also expressed the related Tie-2/Tek gene and, surprisingly,
      its recently cloned ligand gene angiopoietin-1, which was located in chromosome
      8q23.1. In addition, 16% of freshly isolated leukaemia samples were Tie positive.
      Peripheral blood mononuclear cells were Tie negative, but a few Tie positive
      cells were found in immunoperoxidase staining of mobilized peripheral blood stem
      cells. Long-term culture of isolated umbilical cord blood CD34+ Tie+ and CD34+
      Tie- cells indicated that the Tie+ fraction contained a slightly higher frequency
      of cobblestone area forming cells (CAFC). Thus, Tie is expressed on haemopoietic
      progenitor cells and some leukaemic blasts. The coexpression of Tie-2 and
      angiopoietin-1 in megakaryoblastic leukaemia cell lines suggests the existence of
      an autocrine ligand/receptor signalling loop in these cells.

PMID- 9233585
TI  - Macular haemorrhage in adult acute leukaemia patients at presentation and the
      risk of subsequent intracranial haemorrhage.
AB  - Retinal changes are common in adult acute leukaemia patients at presentation, but
      whether they correlate with the risk of subsequent intracranial haemorrhage is
      unknown. A 4-year study has been carried out in 82 newly-diagnosed acute
      leukaemia patients, aged 12-77 years, who were studied prospectively for the
      presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH),
      cotton-wool spots (CWS) and macular haemorrhages (MH). Groups with and without
      these features were compared for their risk of intra-cranial haemorrhage (ICH)
      within the first 30 d following diagnosis. There was no association between the
      incidence of ICH and the presence of IRH, WCH or CWS. However, 6/13 of those with
      MH developed ICH, compared to 6/69 of those without MH (relative risk 5.0, CI 95%
      [2.03-12.33], P=0.003). The only other identifiable risk factor for ICH was the
      M3 subtype of AML, but if the four cases of M3-AML were discounted from analysis,
      MH remained a highly significant risk factor for ICH. Patients with MH should be
      monitored intensively for the development of ICH, and receive priority in the
      allocation of platelets where these are in short supply.

PMID- 9233586
TI  - Successive transformation of chronic myelomonocytic leukaemia into acute
      myeloblastic then lymphoblastic leukaemia, both with minor-bcr rearrangement.
AB  - We report a case of chronic myelomonocytic leukaemia (CMML), which transformed
      first into acute myeloblastic leukaemia (AML) and then into acute lymphoblastic
      leukaemia (ALL). In the AML and ALL phases, chromosome analysis showed a classic
      Philadelphia chromosome (Ph) t(9:22)(q34:q11). Molecular studies showed
      breakpoint cluster region rearrangement between exons e1 and a2 compatible with a
      p190(bcr/abl) breakpoint as observed in Ph-positive lymphoblastic acute
      leukaemia. The minor (m-bcr) rearrangement was also detected during complete
      remission. This observation supports a multistep pathogenesis of leukaemias, and
      that the p190(bcr/abl) breakpoint may influence the course of the disease.

PMID- 9233587
TI  - Robertsonian translocation as an acquired karyotypic abnormality in leukaemia.
AB  - Robertsonian translocations, although relatively common as a constitutional
      genetic aberration, are rarely encountered in leukaemia. We report a case of
      acute myeloid leukaemia which showed an acquired Robertsonian translocation in
      the form of der(14;21) by cytogenetic analysis of leukaemic cells. This was
      confirmed by the PHA-stimulated culture of peripheral blood lymphocytes. A review
      of the literature identifies only eight reported cases of acquired Robertsonian
      translocations in leukaemia. In the majority of cases the Robertsonian
      translocation occurs as a secondary change in a complex abnormal clone, whereas
      in two out of nine patients reported, including ours, it is found as a sole
      karyotypic abnormality.

PMID- 9233589
TI  - Microsatellite instability during the progression of acute myelocytic leukaemia.
AB  - We studied microsatellite instability (MSI) at the onset and during progression
      of 17 individuals with acute myelocytic leukaemia (AML). These included two cases
      of MO, eight with M1 and seven with M4, according to the FAB classification. The
      DNA from diagnostic, remission and relapsed stages of their disease was analysed
      at 69 loci. Two MSI were found in the diagnostic and remission phase paired
      samples (12%), and eight MSI were identified in six of the relapsed phase samples
      (35%). These results indicate that mismatch repair errors such as MSI are
      unimportant at the onset of AML, but might have importance during the progression
      of the disease.

PMID- 9233588
TI  - Childhood acute lymphoblastic leukaemia with ider(21)(q10)t(12;21)(p12;q22): a
      new recurrent abnormality showing ETV6/CBFA2 fusion.
AB  - The cytogenetically unidentifiable t(12;21)(p12:q22), resulting in ETV6/CBFA2
      fusion, is the most frequent chromosomal aberration in childhood acute
      lymphoblastic leukaemia ALL). We report a variant,
      ider(21)(q10)t(12:21)(p12;q22), which was shown to contain double ETV6/CBFA2
      fusions by fluorescence in situ hybridization. This is the second case of such an
      ider(21) in childhood ALL, suggesting that it is a new recurrent abnormality.
      Since the ider(21) is cytogenetically indistinguishable from i(21)(q10) and
      idic(21)(p11), changes associated with similar clinical features as the t(12;21),
      i.e. pre-B-cell ALL and age 1-10 years, we suggest that all ALL displaying these
      changes should be tested for ETV6/CBFA2 fusion transcript.

PMID- 9233590
TI  - Should cytomegalovirus be tested for in both blood and bronchoalveolar lavage
      fluid of patients at a high risk of CMV pneumonia after bone marrow
      transplantation?
AB  - To identify and treat patients at high risk of cytomegalovirus (CMV) pneumonia
      after bone marrow transplantation (BMT), we tested for CMV viraemia weekly, and
      performed broncho-alveolar lavage (BAL) on day 35 post-transplant in 63
      recipients. 36 allogeneic BMT recipients were at a high risk of CMV pneumonia (25
      CMV-seropositive recipients and 11 patients receiving marrow from a CMV
      seropositive donor). Patients with a positive BAL or viraemia received a 14 d
      course of ganciclovir or foscarnet. CMV was detected in 29 (46%) of the 63 BMT
      recipients and excretion of CMV in blood and BAL was significantly linked.
      However, among the 29 patients who excreted the virus, only 10 (35%) shed CMV in
      blood and BAL at the same time: 19 patients (65%) had detectable CMV in blood (11
      patients) or BAL (eight patients) only. Therefore, on the basis of viraemia or
      BAL alone, 21/29 patients (70%) and 18/29 patients (60%), respectively, would
      have received antiviral treatment. BAL increased the CMV detection rate by 13%
      (8/63 patients) relative to viraemia. With this strategy, the incidence of CMV
      pneumonia was reduced to 3% in allografted patients. Only two of the 19
      autografted patients developed fatal CMV pneumonia. We avoided anti-CMV treatment
      in 54% of all the BMT recipients. In conclusion, CMV should be tested for in both
      blood and BAL fluid of BMT recipients at high risk of CMV pneumonia.

PMID- 9233591
TI  - Stem cell mobilization in resistant or relapsed lymphoma: superior yield of
      progenitor cells following a salvage regimen comprising ifosphamide, etoposide
      and epirubicin compared to intermediate-dose cyclophosphamide.
AB  - We analysed the factors influencing the efficacy of peripheral blood stem cell
      (PBSC) collection in patients with lymphoma. Sixty-six patients underwent initial
      PBSC collection following mobilization with chemotherapy plus recombinant
      granulocyte colony-stimulating factor (300 microg/d). Patients were mobilized
      with one of two chemotherapy regimens, either cyclophophamide (3 g/m2 or 4 g/m2)
      (n = 50) or ifosphamide, etoposide and epirubicin (IVE; n = 16). The target of
      collecting > 2.0 x 10(6) CD34+ cells/kg was achieved in 43/66 (65%) patients with
      a median of two apheresis procedures. The IVE plus G-CSF mobilization regimen
      gave a significantly higher median yield of CD34+ cells (8.62 x 10(6)/kg)
      compared with cyclophosphamide plus G-CSF (3.59 x 10(6)/kg) (P = 0.045). The
      median yield of CD34+ cells per leukapheresis was almost twice as high in
      patients receiving IVE (1.94 x 10(6)/kg) compared to cyclophosphamide (1.03 x
      10(6)/kg) (P = 0.035). In a univariate analysis of the factors affecting
      mobilization, the subtype of lymphoma (high-grade NHL) and the mobilization
      regimen were the only factors associated with high CD34+ cell yield. However, in
      a multivariate analysis of factors affecting mobilization including age, lymphoma
      subtype, previous chemotherapy and radiotherapy, only the use of the IVE protocol
      was predictive of a high yield of CD34+ cells. In 13 patients undergoing a second
      mobilization procedure the use of IVE was associated with a significantly higher
      yield of CD34+ cells compared to cyclophosphamide; three patients who failed
      cyclophosphamide plus G-CSF mobilization were able to proceed to transplantation
      following successful mobilization with IVE + G-CSF. These results demonstrate
      that IVE is a highly effective mobilization regimen which is superior to
      cyclophophamide and has the benefit of being effective salvage therapy for
      lymphoma patients.

PMID- 9233592
TI  - Analysis of ETV6 and ETV6-AML1 proteins in acute lymphoblastic leukaemia.
AB  - The t(12;21) is a recurring chromosomal abnormality in acute lymphoblastic
      leukaemias (ALLs) which results in the production of an ETV6-AML1 fusion gene.
      The association between t(12;21) and the deletion of the untranslocated allele of
      ETV6 is among the most frequent abnormalities observed in B-lineage ALLs in
      children. In order to study the proteins encoded by ETV6 and ETV6-AML1, we raised
      polyclonal antibodies directed against a recombinant peptide corresponding to the
      junctional region of ETV6-AML1. Cell lysates from various leukaemic cell lines,
      and from children with B- and T-lineage ALLs, were studied by Western blot. Two
      isoforms of ETV6 protein were detected in normal bone marrow cells and in
      leukaemic cells without 12p alteration: a major form (apparent m.w. 63 kD) and a
      minor one (apparent m.w. 53 kD). In the REH cell line, which expresses the ETV6
      AML1 fusion transcript and no normal ETV6 mRNA, the ETV6 isoforms were absent and
      two new bands were detected corresponding to ETV6-AML1 protein products (apparent
      m.w. 95 and 105 kD). A similar pattern was obtained with blast cells from
      patients with a t(12;21) and a deletion of ETV6. In two patients with a t(12;21)
      but no deletion of ETV6, four bands were detected corresponding to both the
      normal ETV6 and ETV6-AML1 proteins, suggesting that in these cases the second
      ETV6 allele was not inactivated. Surprisingly, the expression pattern of ETV6
      differed widely from patient to patient. In three out of 13 patients without
      t(12;21), the relative intensity of the bands corresponding to ETV6 isoforms in
      blast cells from patients was completely different from normal cells, with a
      marked predominance of the 53 kD isoform. The pattern of ETV6 expression was
      normal in bone marrow from the same patients during remission. These finding
      suggest that ETV6 abnormalities are not restricted to patients with
      translocations or deletions involving this gene.

PMID- 9233594
TI  - Parathyroid hormone related protein (PTHrP) in acute myeloid leukaemia cells.

PMID- 9233593
TI  - Missense mutations at ALA-10 in the factor IX propeptide: an insignificant
      variant in normal life but a decisive cause of bleeding during oral anticoagulant
      therapy.
AB  - Bleeding complications are the most common and unwanted side-effect of oral
      anticoagulant therapy. We report three patients in whom mutations in the factor
      IX (FIX) propeptide were found to cause severe bleeding during coumarin therapy.
      Strikingly, the bleeding occurred within the therapeutic ranges of the
      prothrombin time (PT) and international normalized ratio (INR). In all three
      patients coumarin therapy caused an unusually selective decrease of FIX activity
      (FIX:C) to levels below 1-3%. Upon withdrawal of coumarin, FIX:C increased to
      subnormal or normal values of 55%, 85% and 125%, respectively. Analysis of the
      FIX gene revealed two different missense mutations affecting the Ala-10 residue
      in the propeptide coding region: Ala[GCC] to Val[GTC] in two patients and
      Ala[GCC] to Thr[ACC] in one patient. No further mutation was detected by
      screening 195 random blood donors for mutations at Ala-10, thus excluding a
      frequent polymorphism at this position. The mutation in the FIX propeptide at a
      position which is essential for the carboxylase recognition site causes a reduced
      affinity of the carboxylase enzyme to the propeptide. This effect leads to an
      impaired carboxylase epoxidase reaction which is decisively triggered by the
      vitamin K concentration. Determination of FIX and APTT in addition to PT and INR
      is therefore recommended in coumarin-treated patients with an uncommon bleeding
      pattern.

PMID- 9233595
TI  - Do effector and memory T helper cells also need B7 ligand costimulatory signals?
AB  - Blocking B7 ligand-costimulatory molecules can inhibit a primary T-dependent
      immune response, but whether these interactions also mediate ongoing or memory
      immune responses is less clear. Development of immunotherapies based on blocking
      B7 ligand interactions would be limited if they were effective only at the
      initiation of an immune response. We discuss the conditions under which T helper
      effector and memory cells may or may not require B7 ligand interactions for their
      function.

PMID- 9233596
TI  - Inhibition of acute peritoneal inflammation in rats by a cytokine-induced
      neutrophil chemoattractant receptor antagonist.
AB  - Cytokine-induced neutrophil chemoattractant (CINC), a member of the IL-8
      superfamily of chemokines, is one rat homologue of the three human GRO proteins.
      Neutralizing Abs against CINC have been shown previously to be efficacious in
      several models of inflammation, indicating that CINC is an important
      proinflammatory mediator in vivo. By introducing the N-terminal mutation delta1
      5,ELR>AAR into CINC, we have developed a rat alpha-chemokine receptor antagonist
      (ra) analogous to a previously described mutant of human IL-8. Bacterially
      expressed CINCra had no chemotactic activity itself, but completely blocked the
      activity of physiologic concentrations of CINC when used as an antagonist in
      vitro. Inhibition by CINCra was specific, since it had approximately 10-fold less
      antagonist activity on the related, but distinct rat alpha-chemokine macrophage
      inflammatory protein 2. When coinjected with zymosan into the peritoneal cavities
      of Lewis rats, 100 microg of CINCra inhibited neutrophil influx by approximately
      40%, which was comparable with inhibition caused by polyclonal anti-CINC Abs.

PMID- 9233597
TI  - Microtubule retraction into the uropod and its role in T cell polarization and
      motility.
AB  - Spherical circulating T cells must polarize to extravasate. We have found that
      the polarization process includes a drastic reconfiguration of the tubulin
      cytoskeleton. In spherical T cells, the nucleus is surrounded by microtubules
      radiating from the microtubule organizing center (MTOC). During polarization the
      uropod (a slender posterior appendage) forms at the site of the MTOC. As the
      uropod buds out, the MTOC is carried in its distal tip. The attached microtubules
      retract into the uropod lumen, collapsing like the spokes of an umbrella into a
      compact sheaf. Experiments with microtubule inhibitors show that the retracted
      microtubules do not support the uropod or produce motive force. Instead, the data
      suggest that retraction of the relatively rigid microtubules into the streamlined
      uropod increases T cell deformability, thereby facilitating migration through
      constricted spaces. Microtubule retraction, therefore, may prove to be a strategy
      for accelerating extravasation without disassembly of the microtubule-based
      transport system.

PMID- 9233598
TI  - Telomerase is up-regulated in human germinal center B cells in vivo and can be re
      expressed in memory B cells activated in vitro.
AB  - The extensive proliferation that B lymphocytes undergo in germinal centers could
      compromise generation of long term B cell memory if there occurs shortening of
      the telomeres of germinal center B cells with cell division. Telomere length,
      which is thought to act as a "mitotic clock" for somatic cells that dictates
      cellular senescence, can be preserved by the enzyme telomerase. Human tonsil
      germinal center B cells consistently expressed 100- to 1000-fold higher levels of
      telomerase activity than naive or memory B cells, which had no or very low
      detectable activity, as analyzed by the telomere repeat amplification protocol
      assay. In vitro stimulation of human memory B cells through surface Ig or CD40
      was capable of up-regulating telomerase. The findings suggest that longevity of B
      cell memory is maintained, despite multiple cell divisions in the generation of a
      memory B cell, by up-regulation of telomerase in germinal center and activated
      memory B cells.

PMID- 9233599
TI  - CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G
      by decidual and peripheral blood NK cells.
AB  - Prior studies demonstrated that NK cells isolated from adult peripheral blood
      kill the HLA-A-, HLA-B-, and HLA-C-deficient B lymphoblastoid cell line 721.221,
      but many are unable to kill 721.221 cells transfected with HLA-G, a molecule
      expressed preferentially on fetal cytotrophoblasts. To determine the biologic
      relevance of this recognition, we established NK cell clones from the placenta
      and demonstrate that these NK cells also were unable to kill 721.221 cells
      expressing HLA-G. Recognition of HLA-G by NK cells was prevented in the presence
      of anti-CD94 mAb, implicating CD94/NKG2 as the predominant inhibitory NK cell
      receptor for HLA-G used by decidual NK cells. In contrast, mAbs against the
      killer cell inhibitory receptors recognizing HLA-Cw3-related, HLA-Cw4-related, or
      HLA-Bw4 ligands did not affect NK cell killing of the HLA-G transfectants.

PMID- 9233600
TI  - B cell responses to a peptide epitope: III. Differential T helper cell thresholds
      in recruitment of B cell fine specificities.
AB  - Th cell requirements in the individual stages comprising a murine humoral
      response to a synthetic peptide were examined. Induction of a T-dependent IgM
      response was readily achieved in the presence of unprimed or low numbers of Ag
      primed T cells. In contrast, class switch to the IgG isotype of Abs demanded a
      markedly elevated frequency of primed T cells and occurred concomitantly with B
      cell differentiation into an membrane-bound IgG+ memory population. These results
      indicated that induction and progression of a T-dependent humoral IgG response
      were comprised of a single rate-limiting step represented by that involving Ab
      isotype switch. Subsequent studies established that this also represented the
      principal step where antibody-purifying mechanisms operate. This was enforced by
      imposing a threshold barrier for Th cell recruitment by early Ag-activated B
      cells to enable class switch and consequent retention as the response progresses.
      The quantum of this threshold, however, was not invariant, but, rather, was
      described as a balance between the affinity of B cell receptor for Ag and the
      frequency of Ag-specific Th cells.

PMID- 9233601
TI  - Correction of defective expression in MHC class II deficiency (bare lymphocyte
      syndrome) cells by retroviral transduction of CIITA.
AB  - Retrovirus-mediated gene transfer was used to restore expression to MHC class II
      negative patient cells from complementation group A(II) of MHC class II
      immunodeficiency or bare lymphocyte syndrome (BLS). The cells of these patients
      do not transcribe MHC class II genes due to a defect in the trans-acting factor,
      CIITA. We constructed a vector, pGAG/Ii-CIITA, with the MHC class II-associated
      invariant chain promoter driving CIITA expression. Cocultivation with the virus
      producer line was consistently shown to be the optimal method for infection of
      all cell types. The induction of MHC class II expression after virus infection
      was rapid, and high levels of expression were achieved in cell lines within 1 wk
      of infection. In addition, expression was easily detectable even in peripheral
      blood cells of a BLS patient within a few days. Cell lines maintained in vitro
      for several months remained positive, and the proportion of cells with surface
      expression of DR was correlated with the number of integrated proviruses.
      Moreover, transduced B lymphoblastoid cell lines readily established tumors in
      CB17-scid/scid mice, and the MHC class II-positive cells demonstrated a clear
      competitive advantage in vivo. Ultimately, we hope to use this transduction
      system to restore normal immune function to a BLS patient for which no other
      therapeutic option currently exists.

PMID- 9233602
TI  - Cross-linking of the IgM receptor induces rapid translocation of IgM-associated
      Ig alpha, Lyn, and Syk tyrosine kinases to the membrane skeleton.
AB  - Cross-linking-induced association of membrane IgM (mIgM) with the cytoskeleton is
      well documented. However, its functional significance during B cell activation is
      not yet understood. One possible need for mIgM/cytoskeleton interactions may be
      to recruit the B cell receptor (BCR)-associated signaling molecules to the
      cytoskeletal matrix for the propagation of downstream signaling. We first
      verified whether BCR-associated Ig alpha translocates to the cytoskeleton
      together with mIgM in polyclonal anti-IgM-treated murine B lymphoma cell line,
      BAL17.7.1. Co-capping experiments and the purification of the membrane skeleton
      under conditions that preserve IgM-Ig alphabeta) interactions confirmed that Ig
      alpha translocates to the cytoskeleton as part of the BCR complex. Furthermore,
      two BCR-associated kinases that are known to play critical roles in anti-IgM
      induced B cell signaling, the src family kinase Lyn and the non-src family kinase
      Syk, accumulate in the membrane skeleton shortly after BCR cross-linking, when
      most of IgM and Ig alpha accumulate in this fraction. The kinetics of recruitment
      of the bulk of Ig alpha, Lyn, and Syk into the membrane skeleton appeared to
      precede the accumulation of their hypertyrosine-phosphorylated forms, suggesting
      that activation of the BCR-associated signaling molecules occurs in this
      fraction. These data suggest that cross-linked mIgM translocating to the membrane
      skeleton serves as a vehicle for active signaling molecules to be recruited to
      this vicinity. This may promote B cell activation events by providing high
      affinity interactions between signaling molecules and their substrates supported
      by the cytoskeletal matrix.

PMID- 9233603
TI  - Differential association of phosphatidylinositol 3-kinase with insulin receptor
      substrate (IRS)-1 and IRS-2 in human thymocytes in response to IL-7.
AB  - IL-7 is central to T cell development, inducing proliferation and
      differentiation, but the signal transduction mechanisms by which it accomplishes
      these functions are poorly understood. We demonstrate that, in addition to
      activation of the Jak1 and Jak3 kinases, IL-7 stimulation of human thymocytes
      results in the rapid tyrosine phosphorylation of insulin receptor substrate-1
      (IRS-1) and IRS-2 proteins. We show that the Jak1 and Jak3 kinases are associated
      with both IRS-1 and IRS-2 in thymocytes. However, the pool of Jak3 kinase
      associated with IRS-1 appears to be preferentially activated upon IL-7
      stimulation. We further demonstrate that the 160- to 185-kDa IRS proteins
      associate with the p85 regulatory subunit of phosphatidylinositol 3 (PI3)-kinase
      in an IL-7-dependent manner, although significant differences were evident in the
      levels of PI3-kinase activity associating with each IRS protein. Although IRS-1
      displays a higher degree of basal association, IL-7 induces a much greater
      increase in the activity associated with IRS-2. Lastly, we show that the PI3
      kinase activity associated with the IRS proteins appears to be distinct from that
      bound to the IL-7R, suggesting the existence of separately regulated pools of PI3
      kinase activity. This study suggests that IL-7R signaling diverges at the level
      of the IRS-1 and IRS-2 proteins, possibly with the two branches regulated by Jak3
      and Jak1 activities, respectively.

PMID- 9233605
TI  - High affinity rheumatoid factor transgenic B cells are eliminated in normal mice.
AB  - Although systemic autoimmune diseases can be accompanied by multiple
      autoantibodies, certain specificities are dominant. Presumably, these
      specificities and their cognate Ags have properties that make them particularly
      amenable to autoimmune induction. Rheumatoid factors (RFs) are a dominant class
      of autoantibodies in rheumatoid arthritis and certain other autoimmune syndromes.
      To study the regulation of RFs in normal and autoimmune animals, we previously
      created a RF Ig transgenic model based on an RF isolated from an autoimmune
      MRL/lpr mouse. Using this model, called AM14, we were surprised to find that
      normal mice do not regulate disease-related RF B cells. This raised the question
      of whether RFs in general are not susceptible to tolerance induction, perhaps due
      to the unique properties of serum IgG and its FcRs. Alternatively, RFs can be
      tolerized, and the disease-related RFs are below the affinity threshold for such
      tolerance. To distinguish these possibilities, we generated a second RF
      transgenic model with the same specificity but much higher affinity than AM14. We
      found that, in contrast to AM14, high affinity RF B cells are subject to central
      tolerance, showing that there is not an absolute defect in RF B cell tolerance,
      but, rather, that RF B cell tolerance is affinity dependent even in normal
      animals. This is also the first model in which a disease-related specificity has
      been shown clearly to delete in a system in which Ag-positive and negative mice
      can be produced and compared.

PMID- 9233604
TI  - Ligation of the V7 molecule on T cells blocks anergy induction through a CD28
      independent mechanism.
AB  - Previous studies have demonstrated that a mAb that recognizes the leukocyte
      surface Ag V7 inhibits TCR/CD3-dependent T cell activation. In the current study,
      we demonstrate that in addition to inhibiting T cell proliferation and IL-2
      production, anti-V7 blocks tyrosine phosphorylation of TCR/CD3-associated
      substrates. PMA overcomes this effect, and both PMA and exogenous IL-2 overcome
      anti-V7-mediated inhibition of T cell proliferation and IL-2 production. T cells
      stimulated with anti-CD3 in the absence of CD28 or V7 ligation become
      unresponsive (anergic) to restimulation with anti-CD3; T cells primed in the
      presence of either anti-V7 or anti-CD28 retain their ability to respond to
      restimulation with anti-CD3. When T cells are primed in the presence of optimal
      concentrations of anti-V7 and anti-CD28 Abs, they proliferate normally,
      indicating that the costimulatory signals generated through CD28 dominate the
      inhibitory signals generated through V7. However, as the anti-CD28 stimulus is
      diluted, the V7 effect becomes dominant and proliferation is inhibited. Thus,
      although both anti-V7 and anti-CD28 Abs prevent anergy, they induce distinct,
      competing intracellular signals. Wortmannin, which blocks phosphoinositol 3
      kinase-dependent signaling, has little effect on V7-mediated inhibition, while
      herbimycin, an inhibitor of tyrosine kinase, synergizes with anti-V7 to inhibit T
      cell activation. On the basis of these findings, V7-mediated signals appear to
      inhibit TCR-dependent tyrosine kinases that are required for IL-2 production and
      cellular proliferation.

PMID- 9233606
TI  - ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in
      activation-induced T cell apoptosis.
AB  - Activation-induced cell death (AICD) is initiated by the TCR-dependent up
      regulation of Fas ligand (FasL) mRNA. The subsequently generated soluble or cell
      associated FasL gene products bind Fas, leading to apoptosis of the T cells.
      Although TCR stimulation is essential to initiate AICD, little is known about
      which TCR-initiated second messengers are required for FasL expression. We
      provide evidence in this work that T cells lacking the tyrosine kinase ZAP-70 are
      unable to up-regulate FasL and undergo AICD. Transfection of wild-type ZAP-70
      into the ZAP-70-deficient T cells restores their sensitivity to TCR-induced
      apoptosis, whereas transfection of catalytically inactive ZAP-70 does not. These
      results provide clear evidence that ZAP-70 tyrosine kinase is essential in up
      regulating FasL for TCR-induced apoptosis.

PMID- 9233607
TI  - A novel human CC chemokine PARC that is most homologous to macrophage
      inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but
      not for monocytes.
AB  - By searching the expressed sequence tag (EST) database, we identified partial
      cDNA sequences encoding a polypeptide with significant sequence identity to the
      human CC chemokine macrophage-inflammatory protein-1 alpha (MIP-1 alpha)/LD78
      alpha. We determined the complete cDNA sequence that contained a reading frame of
      89 amino acids with 61% identity to human MIP-1 alpha/LD78 alpha. The mRNA was
      expressed constitutively at high levels in human lung and at low levels in some
      lymphoid tissues. Furthermore, the mRNA was strongly induced in several human
      cell lines, including monocytic U937 cells, by PMA. From these results, we
      designated this novel CC chemokine as PARC from pulmonary and activation
      regulated chemokine. In situ hybridization analyses showed that alveolar
      macrophages, follicular dendritic cells in the germinal centers of regional lymph
      nodes, and peripheral blood monocytes stimulated with LPS express PARC mRNA.
      Using the human CC chemokine yeast artificial chromosome contig that we
      constructed recently, we mapped the PARC gene (SCYA18) within one of the two
      subregions of the CC chemokine gene cluster at chromosome 17q11.2. To investigate
      its biologic activity, the PARC protein was expressed in insect cells. PARC was
      chemotactic for both activated (CD3+) T cells and nonactivated (CD14-)
      lymphocytes, but not for monocytes or granulocytes. Binding analysis using PARC
      fused with alkaline phosphatase-(His)6 showed the presence of a single class of
      receptors for PARC on lymphocytes with a Kd of 1.9 nM and 590 sites/cell. Thus,
      PARC is a novel CC chemokine with a close phylogenic relationship with MIP-1
      alpha/LD78 alpha, but with a highly selective activity on lymphocytes.

PMID- 9233609
TI  - Selective loss of the calcium ion signaling pathway in T cells maturing toward a
      T helper 2 phenotype.
AB  - In the CD4+ T cell lineage, two well-defined differentiated populations are the
      Th1 and Th2 cells, which stem from a common naive T helper precursor (Thp). In
      this study, we begin to dissect the signaling pathways selectively used by Th1 or
      Th2 cells as they mature from a common naive precursor in vitro. We show that the
      maturing Th1 cells mount a vigorous and specific Ca2+ transient upon contact with
      immunogenic ligand, which is enhanced over that of the naive progenitor cells. As
      the cells differentiate toward a Th2 phenotype, they quickly lose the ability to
      engage this pathway, indicating a developmental segregation of intracellular
      signaling utilization. Moreover, altered peptide ligand stimulation of the Th1
      line stimulates a similar Ca2+ transient as native ligand stimulation of the
      naive precursors, consistent with a quantitative difference in intracellular
      signaling by these two peptides. These data provide a direct and sequential
      assessment of a signaling pathway utilization in peripheral T cells as they
      differentiate to their final functional states.

PMID- 9233608
TI  - The effects of IFN-gamma on CD40-mediated activation of B cells from X-linked
      immunodeficient or normal mice.
AB  - B cell activation induced by cross-linking of CD40 is enhanced by costimulation
      with certain T cell-derived cytokines (generally Th2 type), most notably IL-4. We
      show here that the induction of DNA synthesis in normal mouse B cells by anti
      CD40 mAb is also significantly enhanced by supernatants from anti-CD3-activated
      Th1 cells or from primary T cells. In both instances the costimulatory activity
      is specifically abrogated by neutralizing Abs against IFN-gamma. B cells from
      CBA/N immunodeficient (xid) mice are markedly hyporesponsive to most anti-CD40
      Abs, even in the presence of IL-4. These cells do, however, synthesize DNA when
      stimulated by anti-CD40 plus supernatants from anti-CD3-stimulated primary T
      cells, by anti-CD40 plus IFN-gamma (but not IL-4), or by fixed, activated Th1 T
      cells. In all these instances, the mitogenic response of xid B cells is crucially
      dependent on the presence of IFN-gamma. This cytokine also enhanced CD40-induced
      homotypic adhesion of normal and xid B cells and potentiated CD40-mediated
      protection of B cells from spontaneous apoptosis. These data, therefore, indicate
      that IFN-gamma plays an essential role in the activation of B cells by Th1 T
      cells and by naive T cells during the initiation of primary Ab responses. The
      results with CBA/N B cells further suggest that the xid mutation selectively
      affects their capacity to respond to Th2-derived signals, for reasons that remain
      unclear.

PMID- 9233610
TI  - The role of donor and recipient B7-1 (CD80) in allograft rejection.
AB  - Blockade of CD28-mediated T cell costimulatory signals produces effective
      immunosuppression of a variety of T cell-dependent in vivo immune responses,
      including autoimmune disorders and transplant rejection. The soluble fusion
      protein CTLA4Ig, which competitively blocks CD28 ligands B7-1 and B7-2, can
      prevent allograft and xenograft rejection and in some circumstances induce
      transplantation tolerance. To determine the relative roles of B7-1 and B7-2 in
      graft rejection, we have performed islet and cardiac allografts with normal and
      B7-1(-/-) mice in conjunction with selective blocking reagents. We found that the
      absence of B7-1 on donor or recipient tissues leads to a slight prolongation of
      islet allograft survival, but has minimal or no effect on cardiac allograft
      survival. Allograft function is further prolonged in the islet model when both
      donor and recipient lack B7-1, although cardiac allograft survival is not
      prolonged. In the cardiac model, treatment with CTLA4Ig induces long term
      survival in B7-1(-/-) recipients regardless of donor status. In contrast, anti-B7
      2 mAb leads to indefinite allograft survival only when the recipient and donor
      both lack B7-1, indicating that even in the absence of available B7-2, B7-1
      molecules on the donor or recipient cells alone are sufficient to induce graft
      rejection. These data also indicate that B7-1 and B7-2 are the only CD28 ligands
      relevant to cardiac allograft rejection in mice.

PMID- 9233611
TI  - Ontogeny of thymic NK1.1+ cells.
AB  - Thymic NK1.1+ cells are a recently described lymphocyte subset whose biologic
      function is not well defined. There is some controversy as to whether thymic
      NK1.1+ cells mature in a thymic or an extrathymic pathway. In this study, we
      examined the ontogeny of murine thymic NK1.1+ cells utilizing direct examination
      of freshly obtained fetal thymi as well as fetal thymi established in organ
      cultures (FTOC). We found a reproducible peak (5-40%) of NK1.1+ cells,
      demonstrable in day 15 to 16 freshly obtained fetal thymi, which was markedly
      decreased by day 17 of gestation; this peak preceded the appearance of the CD4+
      CD8+ thymocytes by 12 to 24 h. Reverse-transcriptase PCR analysis of NK1.1
      demonstrated its presence as early as day 9 of gestation, thus placing it as one
      of the earliest lymphocytic genes to be transcribed. Utilizing FTOC, we found
      that: 1) day 12 fetal thymi contained a progenitor that can differentiate into an
      NK1.1+ CD4+ CD8+ lymphocyte; 2) NK1.1+ cells dwindle to <5% in FTOC established
      from day 14 thymi; 3) NK1.1+ cells dominate in FTOC supplemented with IL-2; and
      4) most of the NK1.1+ cells seen in FTOC did not express CD3epsilon on their
      surface, except for the FTOC supplemented with IL-12. These findings suggest that
      NK1.1+ cells may play an important role in thymic maturation. Moreover, these
      findings suggest that fetal thymi contain several novel lymphocyte subsets that
      can be induced to overgrow the normal thymocytes upon exposure to certain
      cytokines.

PMID- 9233612
TI  - Activated T cells from draining lymph nodes and an effector site differ in their
      responses to TCR stimulation.
AB  - We previously showed that T cells from the mediastinal lymph nodes (MLN) and lung
      parenchyma of influenza virus-infected mice were functionally remarkably
      different. Here we demonstrate that the differences in cytokine production are
      due to differences in the frequencies of T cells within the activated pool able
      to produce cytokines after TCR stimulation. FACS analysis of T cells from MLN and
      lung tissue demonstrated that T cells expressing any of the activation markers
      tested (LFA-1, CD25, CD44, CD45RB, CD49d, CD62L) always expressed high levels of
      CD44 and LFA-1. These double-high T cells produced >99% of all anti-CD3 mAb
      induced IL-4 and IFN-gamma. Separation of T cells employing mAb against the other
      activation markers in combination with anti-CD44 mAb did not enable further
      fractionation into cytokine producers and nonproducers. Despite their similar
      phenotype, purified double-high lung parenchyma T cells produced markedly higher
      levels of IL-2, IL-4, and IFN-gamma, and contained a higher frequency of cytokine
      producers than their MLN counterparts. Activation of the extracellular signal
      regulated kinase (ERK)-2 in response to TCR cross-linking was detected in double
      high T cells from lung tissue but not MLN. The requirement for ERK signaling for
      maximal IFN-gamma synthesis could nevertheless be demonstrated in both
      populations by blockade with the inhibitor PD98509. Collectively, the data
      suggest that inductive and effector sites differ in the frequency of activated T
      cells able to induce ERK-2-regulated cytokine production after TCR ligation.

PMID- 9233613
TI  - Viral regulation of CD95 expression and apoptosis in T lymphocytes.
AB  - T lymphocyte apoptosis has been observed in vivo in association with viral
      infections. One mechanism known to mediate T cell apoptosis is the CD95 (Fas/APO
      1) Ag apoptotic pathway. CD95 is a cell surface protein that is expressed on
      activated T cells and is capable of relaying an intracellular apoptotic signal
      upon binding with CD95 ligand. CD95-dependent apoptosis has been shown to be
      involved in the homeostatic control of peripheral T cell numbers; however, the
      functional significance of the CD95 apoptotic pathway in the context of viral
      infections has not been clearly elucidated. We show that exposure to a variety of
      viral pathogens causes enhanced CD95 expression in naive peripheral blood cell T
      lymphocytes without leading to enhanced susceptibility to CD95-dependent
      apoptosis. Productive viral infection was not required for this effect.
      Furthermore, using a T cell line and the K562 tumor cell line, we demonstrate
      that cells normally resistant to CD95-mediated killing become susceptible when
      productively infected with virus in a manner that does not rely on increased CD95
      surface expression. These findings demonstrate a regulatory influence of viral
      infection on CD95 expression and activity and suggest that in addition to having
      a role in T cell homeostasis, the CD95 apoptotic pathway might also function to
      eliminate virus-infected T cells.

PMID- 9233614
TI  - Involvement of protein tyrosine kinase p72syk and phosphatidylinositol 3-kinase
      in CD2-mediated granular exocytosis in the natural killer cell line, NK3.3.
AB  - The granular exocytosis pathway is one mechanism by which NK cells and CTLs
      induce cytolysis of target cells. Triggering through adhesion molecules such as
      CD2 and LFA-1 as well as Fc gammaRIII (CD16) can invoke this pathway. CD2 is a
      cell surface glycoprotein present on CTLs and NK cells that plays an important
      role in both cellular adhesion and signal transduction. Here we report that cross
      linking of CD2 as well as CD16 by immobilized Abs enhances granular exocytosis in
      an NK cell line, NK3.3. Herbimycin, a protein tyrosine kinase (PTK) inhibitor, or
      wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI 3-K),
      inhibited completely or almost completely CD2- or CD16-mediated granular
      exocytosis, suggesting the involvement of protein tyrosine kinases and PI 3-K in
      both CD2- and CD16-mediated granular exocytosis. We also observed that cross
      linking of CD2 as well as CD16 enhances p72syk tyrosine kinase activity, and this
      enhancement correlated well with the increased tyrosine phosphorylation of
      several cellular proteins, including the adapter protein Shc. Furthermore, we
      have observed that cross-linking of CD2 as well as CD16 enhances the PI 3-K
      activity associated with the tyrosine-phosphorylated cellular proteins and Shc.
      These results provide insight into the signaling pathways by which triggering of
      CD2 and CD16 on NK cells leads to cytolysis of target cells.

PMID- 9233615
TI  - Neutralizing IL-12 during induction of murine acute graft-versus-host disease
      polarizes the cytokine profile toward a Th2-type alloimmune response and confers
      long term protection from disease.
AB  - Injection of parental spleen cells into BDF1 mice results in a graft-vs-host
      disease (GVHD), the nature of which is critically dependent on the parental
      haplotype. B6-->BDF1 mice develop a Th1-mediated immunosuppressive lethal GVHD,
      whereas DBA/2-->BDF1 mice develop a Th2-dependent chronic GVHD, characterized by
      autoantibody production and glomerulonephritis. In this study we show that
      neutralizing endogenous IL-12 for a brief period during the initiation of acute
      GVHD in B6-->BDF1 mice not only confers long term protection from the acute
      disease, but also permits full repopulation of the recipient with donor B6
      lymphocytes. Antibody-treated animals showed normal T cell proliferation in
      response to Con A stimulation and remained healthy throughout the study.
      Splenocytes from such mice showed reduced in vitro production of IFN-gamma and
      enhanced production of IL-5 and IL-10, suggesting a permanent switch from a Th1
      to a Th2 cytokine response, comparable to that associated with chronic GVHD in
      DBA/2-->BDF1 mice. In contrast to DBA/2-->BDF1 mice, however, anti-IL-12-treated
      B6-->BDF1 mice displayed only mild B cell hyper-responsiveness, as evidenced by a
      modest increase in serum IgG and IgE levels and moderate levels of anti-dsDNA
      Abs. Importantly, however, anti-IL-12-treated B6-->BDF1 mice showed no evidence
      of immune complex-mediated glomerulonephritis. These results demonstrate that
      neutralizing IL-12 is an effective means of preventing acute GVHD and does not
      result in the development of chronic GVHD, which might otherwise limit its
      application.

PMID- 9233616
TI  - Mouse CD1 is mainly expressed on hemopoietic-derived cells.
AB  - The mouse CD1 (mCD1) is a class I-like molecule that is encoded outside the MHC.
      Recent studies demonstrate that mCD1 presents hydrophobic peptides to CD8+ T
      cells and also that it is recognized by a population of NK1.1+ T cells that are
      thought to play an immunoregulatory role because of their ability to secrete IL
      4. It has previously been reported that mCD1 is expressed predominantly by
      intestinal epithelial cells, although most NK1.1+ T cells are located elsewhere.
      We, therefore, have generated new mAbs to mCD1 to investigate its tissue
      distribution. The principal site of mCD1 expression in normal mice is on cells in
      the hemopoietic series, including constitutive expression on nearly all T and B
      cells, on macrophages, and on dendritic cells. Other than bone marrow-derived
      cells, mCD1 is not widely expressed and is not detectable on great majority of
      intestinal epithelial cells. The B cells, but not the T cells, from beta2m
      deficient mice can be recognized by two mCD1 autoreactive T hybridomas.
      Therefore, although we could not detect a beta2m-independent form of mCD1 using
      these mAbs, mCD1 in a different conformation or a mCD1-related molecule is likely
      to be expressed in the absence of beta2m on some cell types. The pattern of
      expression of mCD1 correlates with the distribution of NK1 T cells and is
      consistent with an important Ag-presenting function for this molecule.

PMID- 9233617
TI  - IL-4 and insulin-like growth factor-I inhibit the decline in Bcl-2 and promote
      the survival of IL-3-deprived myeloid progenitors.
AB  - The proto-oncogene product Bcl-2 regulates cell survival in both the immune and
      central nervous systems. We withdrew growth factors from IL-3-dependent murine
      myeloid progenitor cells (factor dependent cell progenitors (FDCP)) and measured
      a time-dependent 80% reduction in endogenous expression of Bcl-2. This decline in
      Bcl-2 is directly associated with a fourfold increase in the apoptotic population
      after 12 h and an eightfold increase after 24 h. Since IL-4 and insulin-like
      growth factor-I (IGF-I) regulate myeloid cell growth, we used IL-3-deprived FDCP
      cells to determine whether IL-4 and IGF-I maintain Bcl-2 expression and prevent
      apoptosis. We demonstrate that IL-4, like IGF-I and IL-3, promotes survival of
      FDCP cells by reducing the apoptotic population. Flow cytometric measurement of
      intracellular Bcl-2 established that IL-4 and IGF-I maintain 10-fold higher
      levels of Bcl-2 than in IL-3-deprived cells. Similarly, Western analysis of Bcl-2
      in lysates of IL-3-deprived myeloid progenitors confirmed that both IL-4 and IGF
      I share with IL-3 the ability to maintain intact Bcl-2 protein. However, IL-4 and
      IGF-I do not change expression of the apoptotic inducer, Bax, although they
      maintain high levels of Bcl-2 that coimmunoprecipitate with Bax. Collectively,
      these data demonstrate that IL-4 and IGF-I, like IL-3, inhibit apoptosis in
      myeloid progenitors and maintain high levels of Bcl-2/Bax heterodimers,
      suggesting that Bcl-2 is a critical convergence point in the signaling pathways
      used by IL-4 and IGF-I.

PMID- 9233619
TI  - Distinct methylation states of the CD8 beta gene in peripheral T cells and
      intraepithelial lymphocytes.
AB  - The CD8 coreceptor is expressed on both immature and mature T cells as either an
      alphabeta heterodimer or an alpha alpha homodimer. Thymocytes and peripheral T
      cells express CD8 alphabeta, whereas TCR alphabeta+ intraepithelial lymphocytes
      (IEL) express CD8 alpha alpha or CD8 alphabeta, and the majority of TCR
      gammadelta+ IEL bear CD8 alpha alpha. The presence of CD8 beta enhances the
      signaling and adhesion properties of the CD8 alphabeta coreceptor and is
      necessary for efficient T cell development in the thymus, but is not required for
      the extrathymic maturation of CD8 alpha alpha+ IEL. To address whether CD8 alpha
      alpha+ IEL express CD8 beta during their development, we examined the methylation
      state of cytosines in the CD8 beta gene 5' regulatory region to identify those
      for which the methylation state inversely correlates with expression of the CD8
      beta protein. We identified four such cytosines that were demethylated in CD8
      beta-expressing thymocytes and T cells. Interestingly, these cytosines were also
      demethylated in CD4+ lymph node T cells that had transiently expressed CD8 beta
      during their development. The methylation state of these cytosines was examined
      in DNA purified from TCR alphabeta+ CD8 alpha alpha+ and TCR alphabeta+ CD8
      alphabeta+ IEL, as well as from TCR gammadelta+ CD8 alpha alpha+ and CD3- CD8
      alpha alpha+ IEL. The methylation pattern for TCR alphabeta+ CD8 alpha alpha+ IEL
      DNA was distinct from that seen for DNA from CD4+ lymph node cells, suggesting
      that TCR alphabeta+ CD8 alpha alpha+ IEL have not previously expressed CD8 beta.
      Analysis of DNA from CD3- CD8 alpha alpha+ IEL indicated that the unique
      methylation pattern of the CD8 beta gene in TCR alphabeta+ CD8 alpha alpha+ IEL
      DNA was not due to transcription of the CD8 alpha gene or the influence of the
      gut microenvironment.

PMID- 9233618
TI  - A functional B cell receptor transgene allows efficient IL-7-independent
      maturation of B cell precursors.
AB  - IL-7 supports the proliferation of B cell precursors, but inhibits their
      maturation to mature surface IgM+ (sIgM+) B cells. This inhibition is thought to
      occur by direct or indirect down-regulation of recombinase genes, preventing the
      B cells from undergoing Ig light chain rearrangements. To directly analyze the IL
      7 inhibitory effects, we studied B cell development and maturation in B cells
      bearing a transgenic (Tg) B cell receptor (BCR). We show here that proliferation
      of Tg B cell precursors is IL-7 dependent both in vivo and in vitro and is
      comparable to that of non-Tg B cell precursors. Tg B cell precursors grown on
      stroma and IL-7 expressed sIgM on >90% of the cells, and a large proportion of
      these cells coexpressed additional maturation markers such as IgD, CD23, CD21,
      and L-selectin, indicating that IL-7 does not inhibit maturation of Tg B cell
      precursors. The presence of the Tg inhibited V(D)J recombination in the cultured
      cells, as very low levels of recombination activating genes 2 (RAG-2) expression
      and endogenous V-Jkappa DNA rearrangements were found. Expression levels of RAG
      mRNAs were not significantly changed after removal of IL-7 from the in vitro Tg B
      cell cultures. In contrast, we found that IL-7 inhibited maturation of non-Tg B
      cell precursors and that removal of IL-7 resulted in a significant increase in
      RAG-2 expression and kappa rearrangements, thus allowing the B cells to express
      sIgM and to mature. These results suggest that IL-7-mediated inhibition of Ig
      gene rearrangement blocks maturation of B cell precursors and that the presence
      of Tg BCR efficiently circumvents this inhibition.

PMID- 9233620
TI  - Family-specific differences in transcription efficiency of Ig heavy chain
      promoters.
AB  - Murine Ig variable region heavy chain genes (V(H)) are grouped into families
      based on coding sequence homology. We observed that the accompanying promoter
      sequences were also conserved in a family-specific manner. Remarkably, no one has
      directly compared the transcription efficiencies of V(H) genes from different
      families. Using an in vitro transcription system, we found that transcription
      efficiencies of different V(H) promoters differed by as much as 70-fold. These
      differences could be attributed to variation in the octamer-heptamer and TATA
      sequences, as well as to the presence or absence of initiator elements. The J558
      family promoter exhibited the highest level of transcription and specifically
      interacted with an Oct-1 dimer not bound by other V(H) promoters. These data
      suggest that differential transcription and regulation of V(H) promoters could
      occur in vivo. The increased transcription efficiency of the J558 promoter
      relative to other V(H) promoters also presents a possible explanation for the
      abundance of J558 sterile transcripts observed before V(H)DJ(H) rearrangement.

PMID- 9233621
TI  - Identification of a STAT6 domain required for IL-4-induced activation of
      transcription.
AB  - Tyrosine phosphorylation of STAT6 in response to IL-4 results in the formation of
      STAT6 homodimers that bind specific DNA elements. Although binding sites for
      STAT6 have been shown to be important for the function of several IL-4-inducible
      promoters, the role of STAT6 in this activation has not been defined. To
      determine whether STAT6 is a transcriptional activator, different portions of the
      carboxyl terminus of STAT6 were fused to the yeast Gal4 protein DNA binding
      domain. Analysis of these chimeric Gal4-STAT6 proteins demonstrates that a 140
      amino-acid proline-rich region of the carboxyl terminus of STAT6 contains a
      region that activates transcription. Truncation mutants of STAT6 that lack this
      domain cannot activate transcription and are capable of repressing transcription
      stimulated by a wild-type STAT6 protein. Strikingly, the ability of IL-4 to
      induce transcription from the Ig germline epsilon promoter is suppressed by
      overexpression of a carboxyl-terminal deletion mutant of STAT6. These studies
      demonstrate that the carboxyl terminus of STAT6 contains an activating domain
      required for the induction of genes by IL-4.

PMID- 9233622
TI  - A truncated heavy chain protein relieves the requirement for surrogate light
      chains in early B cell development.
AB  - Early B cell development depends upon the surface expression of Ig heavy chain
      protein (mu) in a signaling complex known as the pre-B cell receptor (pre-BCR).
      In addition to mu, the pre-BCR consists of the surrogate light chains VpreB and
      lambda5 and the transmembrane signal transduction proteins Ig-alpha and Ig-beta.
      Expression of this complex is associated with changes in surface marker
      expression, gene transcription, and Ig gene rearrangement. Mutations preventing
      the expression of either mu or lambda5 result in developmental arrest, but the
      precise roles of the various components of the pre-BCR remain unclear. Using mice
      transgenic for a surface-expressed, but truncated, form of mu that cannot
      associate with surrogate light chains, we have studied the role of surrogate
      light chains in B cell development. We found that expression of the truncated mu
      transgene resulted in changes in surface marker expression, germline kappa locus
      transcription, and V(D)J recombinase targeting indistinguishable from those
      induced by intact mu protein. These experiments lead us to conclude that
      surrogate light chains, while necessary for the assembly of the wild-type pre
      BCR, are not directly involved in pre-BCR signaling or otherwise required for
      early B cell development.

PMID- 9233623
TI  - RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family,
      is differentially expressed in activated T cells.
AB  - Cross-linking of the CD3 and CD28 molecules on T lymphocytes represents one of
      the most effective signals for T lymphocyte activation and triggering of their
      cytotoxic effector function. To identify genes that are expressed in T cells
      after stimulation, mRNA from T lymphocytes that had been activated by the
      simultaneous stimulation of the CD3 and CD28 trigger molecules was transcribed
      for a differential mRNA display analysis into cDNA and was compared with cDNA
      from CD28- or CD3-activated or resting lymphocytes. Differential expression was
      confirmed subsequently by Northern blot analysis. One of the cDNA fragments
      expressed specifically in CD3- and CD28-activated T cells was designated RP1. The
      predictive protein-coding region of RP1 had a significant homology to members of
      the recently found adenomatous polyposis coli (APC) protein-binding EB1 gene
      family, which codes for yet unknown protein(s). Bacterially expressed RP1 protein
      revealed specific binding to wild-type but not to mutated APC protein. The rapid
      up-regulation of RP1 mRNA in properly activated T cells suggests that this gene
      might belong to the immediate/early gene family, which controls the signal
      transduction cascade downstream of the TCR. As the expression level of the RP1
      gene in activated T cells and a spectrum of tumor-derived cell lines correlates
      with the proliferative status of the cells, members of the EB1-like gene family
      may not only be involved in the tumorigenesis of colorectal cancers but may also
      play a role in the proliferative control of normal cells.

PMID- 9233624
TI  - In vivo footprinting and mutational analysis of the proximal CD19 promoter reveal
      important roles for an SP1/Egr-1 binding site and a novel site termed the PyG
      box.
AB  - CD19 expression begins at the pro-B cell stage of B cell development. As such it
      serves as a good prototype for B cell-specific genes whose expression begins
      shortly after lineage commitment. To understand the molecular mechanisms
      controlling CD19 gene expression, we isolated and functionally characterized the
      CD19 promoter using in vivo footprinting, gel shift assays, and transfection
      studies. Reporter constructs spanning portions of the promoter identified a
      region between -85 and -200 that produced high levels of reporter gene activity
      in lymphoid cells. In vivo footprinting identified protected regions over the
      known high affinity B cell lineage-specific activator protein (BSAP) site, the
      low affinity BSAP site, a SP1/Egr-1 site termed the CD19 GC box, and two novel
      sites named the AT box and PyG box. Phorbol ester treatment of a pre-B cell line
      up-regulated CD19 expression, induced Egr-1, and enhanced the footprint over the
      GC box. Gel shift assays demonstrated SP1 and Egr-1 binding to the CD19 GC box,
      while unknown nuclear proteins bound the PyG and AT boxes. Mutations in the AT
      box or in the BSAP sites did not affect CD19 reporter construct activity, while a
      mutation of the GC box reduced it modestly, and a PyG box mutation reduced it
      dramatically. BSAP failed to trans-activate CD19 promoter constructs in B cells
      or non-B cells, suggesting that cis elements such as the PyG and GC boxes are
      also necessary for high level CD19 promoter expression.

PMID- 9233625
TI  - Somatic mutation in VH complementarity-determining region 2 and framework region
      2: differential effects on antigen binding and Ig secretion.
AB  - The extent to which somatic mutation impairs the Ig complementarity-determining
      region (CDR) and framework region (FRW) structure/function is not clear.
      Previously, we found that the VH CDR2 of the murine T15 Ab is highly sensitive to
      mutation; 56% (26 of 46) of Abs mutated in vitro had reduced or no Ag binding
      capability, and 9% were secretion impaired. Here we test whether the T15 VH CDR2
      structure is unique by mutating the VH CDR2 of the anti-PC-protein murine Ab,
      PCG1-1. PCG1-1 VH is encoded by the M141 gene and is unrelated in sequence or
      structure to that of T15 VH1. The majority (54%, 20 of 37) of PCG1-1 mutants
      carrying one to five mutations in VH CDR2 had reduced or abolished Ag binding,
      while 10% were secretion impaired. Taken together, mutational analysis of the VH1
      and VH M141 genes demonstrates that impaired binding and secretion may be common
      outcomes of CDR2 somatic mutation. We also tested the tolerance of the VH FRW2 of
      T15 to mutation, expecting this sequence-conserved region to be highly sensitive
      to alterations. However, FRW2 accommodated many nonconservative changes, and only
      12% (3 of 25) of secreted mutants had impaired Ag binding. Moreover, mutations in
      FRW2 caused secretion defects in 24% (8 of 33), a frequency twice that of VH CDR2
      mutants. A total of 16 unique secretion mutants have now been identified. These
      findings suggest that B cell losses from somatic mutation may be extensive and
      due to varied causes not all related to Ag binding.

PMID- 9233626
TI  - Effect of mitogenic stimulation and DNA methylation on human T cell DNA
      methyltransferase expression and activity.
AB  - DNA methylation, a mechanism modifying gene expression, is mediated in part by
      the enzyme DNA methyltransferase. Reduced levels of T cell DNA methyltransferase
      have been observed in lupus-like diseases, and increased levels have been
      reported in malignancies. Little is known concerning the regulation of human DNA
      methyltransferase. In this report we demonstrate that mitogenic T cell
      stimulation causes an increase in DNA methyltransferase mRNA and enzyme activity.
      We also show that pharmacologic inhibition of T cell DNA methylation causes an
      increase in the rate of DNA methyltransferase mRNA transcription and a
      corresponding increase in mRNA levels and enzyme activity. This suggests that DNA
      methyltransferase is itself regulated in part by DNA methylation status, possibly
      representing a feedback mechanism. DNA methylation inhibition also resulted in an
      increase in Ha-ras and c-jun mRNA levels, overexpression of which increases DNA
      methyltransferase in murine systems. These results thus identify two mechanisms
      regulating levels of human T cell DNA methyltransferase and raise the possibility
      that abnormalities in either could contribute to disorders associated with
      altered DNA methylation.

PMID- 9233627
TI  - Virtually identical enhancers containing a segment of homology to murine 3'IgH
      E(hs1,2) lie downstream of human Ig C alpha 1 and C alpha 2 genes.
AB  - We have isolated sequences downstream of human Ig C alpha 1 and C alpha 2 genes
      and have identified two enhancers in these regions. One enhancer is located
      approximately 9 kb downstream of C alpha 1, and the second enhancer is located
      approximately 11 kb downstream of C alpha 2. These approximately 1.6-kb enhancers
      are virtually identical to each other except for varying numbers of a
      approximately 53-bp motif. The C alpha 2-associated enhancer contains four copies
      of this motif in tandem, whereas the C alpha 1-associated enhancer has only a
      single copy. Within the human enhancers is a 177-bp segment that is homologous to
      a 191-bp segment of one of four enhancers from the 3' regulatory region of murine
      (and rat) DNA, namely 3'IgH-E(hs1,2). Like the murine and rat enhancers, both
      human enhancers are flanked by inverted repeats; furthermore, the human enhancers
      generally appear to be inverted with respect to each other. The evolutionarily
      conserved region of homology has substantial core enhancer activity. Contained
      within this region are the single octamer and one copy of the approximately 53-bp
      motif, both of which contribute to the activity of the full-length enhancer. A
      comparison of the DNA sequences and the results of transient transfection assays
      imply that the human C alpha-associated enhancers may be regulated (in part)
      differently than the murine enhancer 3'IgH-E(hs1,2).

PMID- 9233628
TI  - Involvement of Rel, Fos, and Jun proteins in binding activity to the IL-2
      promoter CD28 response element/AP-1 sequence in human T cells.
AB  - CD28 is an important costimulatory molecule in the activation of human T cells.
      Costimulation of T cells through both the Ag receptor and CD28 leads to high
      level IL-2 production, which is vital to the development of an immune response in
      vivo. Previous reports have suggested the CD28 stimulation contributes to the
      activation of the IL-2 promoter by up-regulating the activity of several
      transcription factors, including AP-1 and nuclear factor-kappaB (NF-kappaB)/Rel
      family members as well as an uncharacterized transcription factor called CD28
      response complex. While several lines of investigation have suggested that NF
      kappaB/Rel family members make up the CD28 response complex transcription factor,
      other work has not supported this conclusion. Recent studies suggest that the
      CD28 response element (CD28RE) does not function independently but works instead
      in conjunction with the adjacent promoter proximal AP-1-binding site and this
      hypothesis is confirmed here. Also in the current study, binding activity to the
      CD28RE/AP-1 sequence of the IL-2 promoter is evaluated. Although four specific
      complexes can be detected binding to this sequence, only one of these complexes
      is specific for both the CD28RE and the adjacent AP-1 site. Of the NF-kappaB/Rel
      family members tested, this CD28RE/AP-1-specific complex contains predominantly c
      Rel, despite the fact that both p50 and RelA can efficiently bind to the CD28RE.
      c-Fos and c-Jun are also found in this CD28RE/AP-1-specific complex. These data
      indicate that functional complexes encompassing both the CD28RE and the AP-1
      binding sites influence IL-2 promoter activity in CD28-costimulated T cells.

PMID- 9233629
TI  - Single-cell cytokine analysis of gamma delta T cell responses to nonpeptide
      mycobacterial antigens.
AB  - TCR gamma delta T cells are considered important in the rapid immune response to
      intracellular infection. We investigated the early response of peripheral blood
      gamma delta T cells to the nonpeptide Ag isopentenyl pyrophosphate and to its
      synthetic analogue ethyl pyrophosphate. In healthy donors, an increase in the
      number of gamma delta T cells was detected as soon as 4 days after stimulation
      with the nonpeptide Ags. Single-cell analysis of cytokine production was
      performed by intracellular staining of IFN-gamma and IL-4. gamma delta T cells
      were found to rapidly expand and produce IFN-gamma in response to nonpeptide Ags.
      Furthermore, IL-12 augmented the IFN-gamma response. In contrast, gamma delta T
      cells from the majority of HIV+ donors did not expand or express IFN-gamma in
      response to nonpeptide Ags, even in the presence of IL-12. These findings
      indicate a role for nonpeptide-reactive gamma delta T cells in effective cell
      mediated immunity for intracellular pathogens.

PMID- 9233630
TI  - Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can
      induce CTL and tumor suppression in syngeneic hosts.
AB  - In this analysis, we examined whether peptides derived from a wild-type murine
      proto-oncogene, c-erbB-2, function as tumor rejection Ags. Expression of murine c
      erbB-2 examined by means of reverse transcription-PCR was observed in several
      normal adult tissues, such as intestine, kidney, and testis. We then transduced
      human and murine c-erbB-2 cDNA into two mutually noncross-reactive fibrosarcoma
      lines of BALB/c origin, CMS7 and CMS17. In BALB/c mice immunized with CMS17HE
      (CMS17 transduced with human c-erbB-2 cDNA), the growth of subsequently
      challenged CMS7HE (CMS7 transduced with human c-erbB-2 cDNA) was significantly
      suppressed. CTL against human c-erbB-2-expressing cells were generated from
      BALB/c spleen cells in vivo and in vitro sensitized by CMS17HE. The CTL activity
      was also directed against murine c-erbB-2-expressing cells, CMS7ME and CMS17ME,
      and was blocked by anti-CD8 or anti-Kd mAbs. A series of peptides of human or
      murine c-erbB-2 compatible with the Kd binding motif was synthesized. The CTL
      were reactive with P1.HTR (H-2d) pulsed with three of these peptides, p63-71
      (human c-erbB-2 derived), p63-71(A) (murine c-erbB-2 derived), and p780-788
      (common for human and murine c-erbB-2). Spleen cells immunized in vivo and in
      vitro with syngeneic spleen cells pulsed with these peptides became cytotoxic for
      CMS17HE and/or CMS17ME, but not CMS17neo (CMS17 transduced with control vector).
      The growth of CMS7ME was suppressed in mice immunized with the murine c-erbB-2
      derived peptide, p63-71(A) or p780-788. There was no apparent pathologic change
      in mice that rejected CMS7ME after vaccination with these peptides.

PMID- 9233631
TI  - Lipopolysaccharide-induced IL-12 expression in the central nervous system and
      cultured astrocytes and microglia.
AB  - We examined whether the cytokine IL-12 could be induced locally in the brain or
      in glial cell cultures following LPS treatment. In the brain, expression of IL-12
      p35 mRNA was constitutive and did not alter following i.p. injection of LPS. In
      contrast, IL-12 p40 mRNA was only detectable in the brain of mice given two
      staggered injections of LPS. Dual labeling in situ analysis revealed IL-12 p40
      RNA-positive cells scattered throughout the brain parenchyma, with a small number
      of these cells being identified as astrocytes, while the majority of IL-12 p40
      RNA-expressing cells appeared to be microglia. In cultured microglia or
      astrocytes, LPS and to a much lesser degree IL-1beta, but not IFN-gamma or TNF
      alpha, induced the expression of IL-12 p40 mRNA. Numerous glial fibrillary acidic
      protein-immunopositive cells colabeled for IL-12 p40 RNA; indicating that LPS
      stimulated astrocytes expressed IL-12 in vitro. Immunoblot analysis of lysates
      from LPS-treated astrocytes revealed the presence of multiple species of 40, 43,
      75, and 120 kDa containing the IL-12 p40 protein. Finally, secretion of the IL-12
      p75 heterodimer was detectable by ELISA from astrocytes treated with LPS plus IFN
      gamma, but not with LPS alone. The findings indicate that IL-12 gene expression
      can be activated in the brain, with the resident glial cells being a prodigious
      source of this cytokine. The localized production of IL-12 may have a significant
      impact on the development of cell-mediated immune responses within the central
      nervous system.

PMID- 9233632
TI  - Differential induction of apoptosis by virulent Mycobacterium tuberculosis in
      resistant and susceptible murine macrophages: role of nitric oxide and
      mycobacterial products.
AB  - Resistance and susceptibility of macrophages to mycobacteria are under the
      control of the Bcg/Nramp1 gene, which also controls the NO- production in
      response to macrophage activators. There is recent evidence indicating that
      mycobacteria induces apoptosis in infected macrophages. Using murine macrophage
      lines, congenic at the Bcg/Nramp1 gene, this report shows that B10R are more
      prone than B10S macrophages to undergo apoptosis after exposure to live virulent
      Mycobacterium tuberculosis H37Rv (Mtb) or PPD, as determined by cell viability,
      DNA fragmentation, hypoploidy, and the terminal deoxynucleotide transferase dUTP
      biotin nick-end labeling assay. Induction of apoptosis correlated with NO-
      production. Aminoguanidine and anti-TNF-alpha inhibited NO- production and
      apoptosis. B10R and B10S macrophages were equally affected by sodium
      nitroprusside, a donor of NO-, but its effect, mainly in B10R cells, was enhanced
      by the presence of Mtb. Nonvirulent mycobacteria induced lower levels of NO- and
      did not cause cell death. Killed Mtb, mannose-capped lipoarabinomannan (ManLAM),
      and LPS rescued macrophages from apoptosis albeit induce NO-. These findings
      suggest the existence of opposite pathways: metabolically active mycobacteria
      promotes apoptosis whereas their structural components inhibit it. Apoptosis may
      be a critical mechanism by which Nramp1 gene controls the macrophage infection
      with virulent mycobacteria.

PMID- 9233633
TI  - Binding of malaria T cell epitopes to DR and DQ molecules in vitro correlates
      with immunogenicity in vivo: identification of a universal T cell epitope in the
      Plasmodium falciparum circumsporozoite protein.
AB  - The efficacy of a malaria peptide vaccine would be enhanced by the inclusion of a
      parasite-derived universal T cell epitope to ensure that all vaccinees develop
      parasite-specific cellular and humoral immunity. Two circumsporozoite (CS)
      protein T cell epitopes, previously identified by CD4+ T cell clones derived from
      Plasmodium falciparum sporozoite-immunized volunteers, were studied to determine
      their HLA class II binding potential. One epitope, located in amino acid (aa) 326
      345 of the P. falciparum (NF54 strain) CS protein, was "universal" in that it
      could bind to multiple DR and DQ molecules in vitro. In contrast, the second
      epitope, T1, which is located in the CS repeat region, was recognized by T cells
      in the context of DQ6 (DQB1*0603) and did not bind with high affinity to any of
      the class II molecules tested in the peptide binding assays. The in vitro
      patterns of peptide/HLA interactions correlated with immunogenicity in vivo. A
      multiple antigen peptide (MAP) containing the aa 326-345 epitope elicited
      responses in eight inbred strains (H-2(a,b,d,k,p,q,r,s)), while the T1 MAP was
      recognized by only a single haplotype, H-2b. The combination of the universal aa
      326-345 T cell epitope and the T1 repeat in a di-epitope MAP overcame the genetic
      restriction to the P. falciparum CS repeat region and elicited antisporozoite Ab
      responses in all of the MAP-immunized mice. Synthetic peptide malaria vaccines
      containing the aa 326-345 universal T cell epitope would be expected to elicit
      parasite-specific immune responses in both sporozoite-primed and naive
      individuals of diverse genetic backgrounds.

PMID- 9233634
TI  - Immunodominance of a single CTL epitope in a primate species with limited MHC
      class I polymorphism.
AB  - MHC class I molecules play a crucial role in immunity to viral infections by
      presenting viral peptides to cytotoxic T lymphocytes. One of the hallmarks of MHC
      class I genes in outbred populations is their extraordinary polymorphism, yet the
      significance of this diversity is poorly understood. Certain species with reduced
      MHC class I diversity, such as the cotton-top tamarin (Saguinus oedipus), are
      more susceptible to fatal viral infections. To explore the relationship between
      this primate's limited MHC class I diversity and its susceptibility to viruses,
      we infected five cotton-top tamarins with influenza virus. Every tamarin
      recognized the same immunodominant CTL epitope of the influenza nucleoprotein.
      Surprisingly, this nucleoprotein peptide was bound by Saoe-G*08, an MHC class I
      molecule expressed by every cotton-top tamarin. Two tamarins also made a
      subdominant response to an epitope of the matrix (M1) protein. This peptide
      appeared to be bound by another common MHC class I molecule. With the exception
      of an additional subdominant response to the polymerase (PB2) protein in one
      individual, no other influenza-specific CTL responses were detected. In
      populations or species with limited MHC class I polymorphism like the cotton-top
      tamarin, a dependence on shared MHC class I molecules may enhance susceptibility
      to viral infection, since viruses that evade MHC class I-restricted recognition
      in one individual will likely evade recognition in the majority of individuals.

PMID- 9233635
TI  - The hepatitis B virus-specific CTL responses induced in humans by lipopeptide
      vaccination are comparable to those elicited by acute viral infection.
AB  - We have previously described the development of a lipopeptide-based vaccine,
      Theradigm-HBV, capable of inducing CTL responses in humans. This vaccine
      incorporates the HLA-A2.1-restricted CTL epitope hepatitis B core Ag 18-27,
      linked to the universal helper T lymphocyte (HTL) epitope tetanus toxoid (TT) 830
      843. Herein, we report the results of a phase I trial designed to examine the
      effects of Theradigm-HBV dose and regimen on the magnitude and duration of the
      memory CTL response. A total of four injections of up to 5 mg/dose were found to
      be a safe and effective means of generating substantial memory CTL responses.
      Precursor frequency analysis demonstrated CTL responses of similar magnitude to
      those previously observed in patients who successfully cleared hepatitis B virus
      infection and to influenza-specific memory CTL responses induced by natural
      exposure to influenza virus. Theradigm-HBV induced CTL responses that persisted
      for more than 9 months after the last injection. HTL responses were associated
      with significant CTL responses, and sustained HTL activity was necessary for
      development of persistent memory CTL activity. These results represent the first
      demonstration of the importance of HTL activity for development of long-lived
      memory CTL responses in humans. In conclusion, our results show that lipopeptides
      safely induce specific CTL activity in humans of such magnitude and persistence
      as to be of potential therapeutic significance.

PMID- 9233637
TI  - Identification of an inhibitor targeting macrophage production of monocyte
      chemoattractant protein-1 as TGF-beta 1.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is expressed in a diverse range of
      cells in response to various pathologic stimuli, whereas little is known about
      endogenous inhibitors of MCP-1 expression. I sought negative regulators of MCP-1
      in culture medium conditioned by several cell lines and found that glomerular
      mesangial cells exclusively secrete a factor that inhibits expression of MCP-1 by
      activated macrophages. Treatment of J774.2 macrophages with conditioned medium
      from mesangial cells blunted the induction of MCP-1 by LPS. Even after the
      induction, subsequent treatment of macrophages with the conditioned medium down
      regulated the MCP-1 expression. Medium conditioned by normal rat glomeruli
      contained a similar inhibitory activity that was enhanced in regenerating
      glomeruli, where mesangial cells are activated. The activity of the conditioned
      medium was not diminished, but enhanced by heat treatment, which was consistent
      with the unique property of TGF-beta family of molecules. Indeed, the mesangial
      cell-derived medium contained active TGF-beta 1. An anti-TGF-beta 1 neutralizing
      Ab abolished the inhibitory effect exerted by the mesangial cell medium, and
      externally added TGF-beta 1 suppressed the MCP-1 expression by macrophages at
      both mRNA and protein levels. The inhibitory effect of TGF-beta 1 on MCP-1 was
      observed in other macrophage cell lines, RAW264.7 and NR8383, and peritoneal
      macrophages, but not in fibroblastic cell line NRK49F. Treatment of J774.2
      macrophages with TGF-beta 1 inhibited LPS induction of c-jun that was found to be
      crucial for the MCP-1 expression. These data demonstrate that TGF-beta 1
      functions as an inhibitor of MCP-1 expression in macrophages possibly via down
      regulation of c-Jun/activator protein-1.

PMID- 9233638
TI  - Increased tolerance to endotoxin by granulocyte-macrophage colony-stimulating
      factor-deficient mice.
AB  - The contribution of granulocyte-macrophage CSF (GM-CSF) to endotoxin-mediated
      septic shock has been assessed by treating GM-CSF-deficient mice with LPS.
      Hypothermia and loss in body weight were markedly attenuated in LPS-treated GM
      CSF-deficient mice compared with similarly treated control mice; moreover, the
      levels of circulating IFN-gamma, IL-1alpha, and IL-6 were lower in LPS-treated GM
      CSF-deficient mice than LPS-treated control mice. Intriguingly, the peak levels
      of TNF-alpha in response to LPS treatment were the same in the serum of GM-CSF
      deficient mice and control mice, although in GM-CSF-deficient mice, TNF-alpha
      persisted longer. Activation of macrophages by LPS, resulting in expression of
      cytokines including TNF-alpha and IL-1, is thought to underlie endotoxin-mediated
      effects. Accordingly, the response of peritoneal macrophages from GM-CSF
      deficient mice to LPS was studied in vitro. LPS-stimulated peritoneal macrophages
      from GM-CSF-deficient mice produced significantly less IL-1alpha and nitric oxide
      than macrophages from wild-type mice, although there was no difference in TNF
      alpha production. Collectively, these observations indicate that GM-CSF
      contributes to cytokine production in LPS-mediated septic shock, and that the
      attenuated production of these secondary cytokines (IFN-gamma, IL-1alpha, and IL
      6) may contribute to the endotoxin-resistant phenotype of GM-CSF-deficient mice.

PMID- 9233636
TI  - Time-dependent induction of protective anti-influenza immune responses in human
      peripheral blood lymphocyte/SCID mice.
AB  - The human (hu) PBL/SCID mouse model has the potential to provide a powerful tool
      for the study of human immune function. However, at peak engraftment (4-8 wk
      postinjection), recovered human T cells are largely unresponsive to foreign Ag
      and have converted to an activated/memory-type phenotype. Here we show that this
      conversion is not a prerequisite for engraftment because at early stages (2 wk) a
      substantial fraction of human T cells detected in SCID peripheral blood retains
      the unactivated/naive phenotype of donor PBL. This early stage is also associated
      with a TCR repertoire in both the CD4 and CD8 subsets that is similar to that in
      the donor. Importantly, we show that strong HLA class I allele- and peptide
      specific cytotoxic T lymphocyte as well as humoral responses can be generated in
      this model when human cells encounter Ag (infection with influenza A) at early,
      but not late, stages in engraftment. This early human response was also
      functional, as partial protection against influenza-induced pathology and death
      in SCIDs was observed. Taken together, these results demonstrate that the
      huPBL/SCID model can support the generation of potent and specific CTL and
      humoral responses provided that Ag is introduced early, presumably before the
      time-dependent generalized xenoactivation of engrafted human cells.

PMID- 9233639
TI  - Suppression of concanavalin A-induced hepatitis in IFN-gamma(-/-) mice, but not
      in TNF-alpha(-/-) mice: role for IFN-gamma in activating apoptosis of
      hepatocytes.
AB  - Con A-induced hepatitis (Con A-hepatitis) is a hepatitis model in which hepatic
      injury is supposed to be caused by cytokines from activated T cells. To elucidate
      the pathogenesis of this disease, we analyzed the roles of IFN-gamma and TNF
      alpha using deficient mice of these cytokines. Development of hepatitis was
      reduced significantly in IFN-gamma(-/-) mice, while susceptibility of TNF-alpha(
      /-) mice was not changed. Interestingly, apoptotic cell death was observed in the
      affected livers of control or TNF-alpha(-/-) mice, but not in those of IFN-gamma(
      /-) mice. Fas mRNA expression was increased in the livers of hepatitis mice, but
      less abundantly in those of IFN-gamma(-/-) mice. Since apoptosis of liver cells
      was rarely observed in Con A-treated lpr/lpr mice, involvement of the Fas-Fas
      ligand system in this apoptotic process was suggested. These observations suggest
      that IFN-gamma plays a central role in Con A-hepatitis by activating Fas-induced
      apoptosis of liver cells.

PMID- 9233640
TI  - Evidence that the two C1q binding membrane proteins, gC1q-R and cC1q-R, associate
      to form a complex.
AB  - Two types of widely coexpressed, highly acidic, cell membrane binding proteins
      that display preferential domain specificity for C1q have been described: a 60
      kDa calreticulin homologue, designated cC1q-R, that binds to the collagen-like
      "stalk" and a 33-kDa glycoprotein with affinity for the globular "heads" (gC1q
      R). Although the two molecules are known to be coexpressed on all cell types
      examined to date and often coelute during purification, there is no direct
      evidence showing that they associate with each other either on the membrane or
      when examined in a purified system. In this report we present the first evidence
      that 1) biotinylated cC1q-R binds to recombinant as well as native gC1q-R, as
      assessed by solid phase ELISA; 2) binding sites for cC1q-R are located within N
      terminal residues 76 through 93 of the mature form of gC1q-R and within residues
      204 through 218; 3) this interaction is inhibited by two mAbs, 60.11 and 46.23,
      that recognize primarily epitopes within the N terminus of gC1q-R corresponding
      to residues 74 through 96 and by mAb 74.5.2 that recognizes epitopes within
      residues 204 through 218; and 4) biotinylated cC1q-R binds to microtiter-fixed
      Raji and K562 cells, and this interaction is inhibited by mAb 60.11. Furthermore,
      coimmunoprecipitation analysis of Raji cell membranes with anti-gC1q-R mAbs
      showed the presence of cC1q-R in addition to gC1q-R. Taken together, the evidence
      suggests that cC1q-R is able to form a complex with gC1q-R and may associate with
      gC1q-R on the cell surface.

PMID- 9233641
TI  - The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal disorder.
      Fibroplasia and deposition of extracellular matrix are dependent, in part, on
      angiogenesis. We postulated that an imbalance exists in the expression of
      angiogenic (IL-8) vs angiostatic (IFN-gamma-inducible protein (IP-10)) CXC
      chemokines, which favors net angiogenesis in IPF. To test this hypothesis, we
      obtained open lung biopsies either from normal patients undergoing thoracic
      surgery for reasons other than interstitial lung disease (control) or from
      patients with IPF. We found that levels of IL-8 were greater from tissue
      specimens of IPF patients then from those of controls. In contrast, IP-10 levels
      were higher from tissue specimens obtained from control subjects than from those
      from IPF patients. When IL-8 or IP-10 was depleted from IPF tissue specimens,
      tissue-derived angiogenic activity was markedly reduced or enhanced,
      respectively. Immunolocalization of IL-8 demonstrated that the pulmonary
      fibroblast (PF) of IPF lung was the predominant cellular source of IL-8. Isolated
      PF from IPF patients constitutively produced more IL-8 and less IP-10 than
      control PF. Conditioned media from IPF-PFs demonstrated constitutive angiogenic
      activity that was attributable, in part, to IL-8. Depletion of IP-10 from IPF-PF
      CM resulted in an increase in corneal neovascularization. These findings support
      the notion that IL-8 and IP-10 are important factors that regulate angiogenic
      activity in IPF.

PMID- 9233642
TI  - Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the
      principal intermediate in IFN-gamma-induced suppression of exocytosis.
AB  - IFN-gamma regulates various aspects of rodent peritoneal mast cell function,
      including mediator release, cell growth, TNF-alpha-mediated cytotoxicity, and MHC
      class II expression. We investigated whether the suppressive action of IFN-gamma
      on IgE/Ag-mediated degranulation of mast cells is mediated via synthesis of
      nitric oxide. Incubation of mouse peritoneal cells with L-NMMA, an inhibitor of
      nitric oxide synthase, or in medium lacking the nitric oxide precursor L-arginine
      reversed the inhibitory effect of IFN-gamma on Ag-induced serotonin release.
      Furthermore, the nitric oxide donors sodium nitroprusside and S
      nitrosoglutathione inhibited degranulation, and this effect was direct, since it
      was seen equally on purified and unfractionated mast cells and occurred
      independently of IFN-gammaR expression. Additional experiments revealed that
      accessory cells in peritoneal cell populations were the principal target for the
      action of IFN-gamma and the main source of nitric oxide; the cytokine was more
      potent on unfractionated compared with purified mast cells, and IFN-gamma induced
      detectable nitrite production in mixed peritoneal cells, but not in purified mast
      cells. These studies show that IFN-gamma induces nitric oxide production in
      peritoneal cell populations, and that synthesized nitric oxide directly inhibits
      the IgE-mediated secretory function of mast cells. The activation of nitric oxide
      producing cells in the tissue microenvironment may be important in the control of
      mast cell-dependent allergic reactions.

PMID- 9233643
TI  - Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z
      receptor of human macrophages.
AB  - Extracellular ATP (ATPe) is known to cause release of processed IL-1 beta from
      LPS-treated macrophages and microglial cells. IL-1 beta release is fast and
      thought to be associated with cell death. We have reinvestigated this process to
      identify 1) the purinergic receptor involved; 2) the relationship to cell death;
      and 3) pharmacologic agonists or antagonists able to modulate IL-1 beta release.
      Our data confirm that ATPe is a powerful stimulus for IL-1 beta release from LPS
      treated human macrophages; however, we also show that IL-1 beta release is not
      necessarily associated with cell death, as it occurs at lower ATP concentrations
      and much earlier than leakage of cytoplasmic markers. The selective purinergic
      P2Z receptor agonist benzoylbenzoyl ATP was at least one order of magnitude more
      powerful than ATP, but also had a strong cytotoxic effect. 2-Methylthio-ATP was
      equipotent as ATPe at the optimal concentration of 1 mM, but markedly inhibitory
      at higher concentrations. The irreversible P2Z blocker-oxidized ATP completely
      inhibited ATPe-induced IL-1 beta release. IL-1 beta release also was inhibited by
      increasing the K+ concentration of the incubation medium. These data suggest that
      ATPe triggers IL-1 beta via the purinergic P2Z receptor recently shown to be
      expressed by human macrophages and identified as a new member of the P2X family
      (P2X7), and provide pharmacologic tools for the modulation of IL-1 beta release
      in vitro and, possibly, in vivo.

PMID- 9233644
TI  - Differential effects of the T helper cell type 2-derived cytokines IL-4 and IL-5
      on ligand binding to IgG and IgA receptors expressed by human eosinophils.
AB  - Increased numbers of eosinophilic granulocytes that exhibit an activated
      phenotype are found in bronchial tissue and bronchial alveolar lavage fluid of
      patients with allergic asthma. Little is known about the processes that lead to
      activation of eosinophils in vivo, but Igs might be important stimulants. In the
      present study we investigated the capacity of human eosinophils to interact with
      beads coated with human serum IgG or IgA. Binding of IgG/IgA-coated beads to
      eosinophils from normal donors appeared to be dependent on priming with Th2
      derived cytokines. Priming with granulocyte-macrophage CSF, IL-4, or IL-5 is
      required for eosinophils to form rosettes with IgA-beads. IL-4 priming resulted
      in a fast and transient effect on binding of IgA-beads, whereas the effect of IL
      5 priming was slower and longer lasting. The expression of Fc alphaR (CD89) was
      low compared with that on neutrophils, and experiments with the blocking mAb My43
      (CD89) showed no inhibition of rosette formation between eosinophils and IgA
      coated beads. However, polymeric myeloma IgA effectively inhibited the rosette
      formation of IgA-coated beads to eosinophils. Binding of IgG-beads could only be
      primed with granulocyte-macrophage CSF and IL-5, not with IL-4. These data are
      concurrent with the hypothesis that Th2-derived cytokines spatially produced at
      the side of an allergic inflammatory response can direct eosinophils to a rather
      restricted primed phenotype by IL-4 or to a more generalized primed phenotype by
      IL-5.

PMID- 9233645
TI  - Eotaxin-induced eosinophil migration in the peritoneal cavity of ovalbumin
      sensitized mice: mechanism of action.
AB  - Cell accumulation in response to i.p. administration of the C-C chemokine,
      eotaxin, was studied in vivo. OVA-sensitized mice, exhibiting blood eosinophilia,
      had greater eosinophil (Eo) accumulation in response to 500 ng of eotaxin at 6 h
      (vehicle-injected, 3.0 +/- 0.5 x 10(5); eotaxin-injected, 8.6 +/- 1.0 x 10(5))
      than nonsensitized, eotaxin-injected mice (2.5 +/- 0.4 x 10(5)). A nonspecific
      neutrophil migration was observed in both vehicle- and eotaxin-injected cavities.
      The number of intact mast cells in the peritoneal lavages after eotaxin injection
      was significantly lower than that in vehicle-injected animals (0.8 +/- 0.3 x
      10(4) vs 2.8 +/-0.6 x 10(4), respectively). When endogenous peritoneal mast cells
      were depleted with compound 48/80 before eotaxin administration, there was a 51%
      reduction in Eo accumulation. This suggests an important role for endogenous mast
      cells in mediating the actions of eotaxin. The potential role of mast cell
      mediators in the actions of eotaxin was also investigated. Pretreatment with
      histamine-H1 or serotonin antagonists reduced Eo migration in response to eotaxin
      by 50 to 65%. Further, following pretreatment with a specific mAb against TNF
      alpha, only nonspecific neutrophil influx was attenuated. Using neutralizing
      mAbs, Eo migration was found to be dependent on the adhesion molecules P- and E
      selectin and CD11b. Eo accumulation was also sensitive to dexamethasone, with
      doses as low as 0.2 mg/kg inducing 100% inhibition. This study provides useful
      insight into the mechanisms of action of eotaxin.

PMID- 9233646
TI  - Soluble IL-6 receptor leads to a paracrine modulation of the IL-6-induced hepatic
      acute phase response in double transgenic mice.
AB  - There is a growing number of soluble agonistic (IL-6, ciliary neurotropic factor,
      IL-11, and glia-derived neurotropic factor receptors) and antagonistic (IL-1 and
      TNF receptors) receptor proteins, modulating the biological functions of their
      cognate ligands. The physiologic role of these receptor molecules in vivo is
      unclear. In particular, it is not known how the specificity of function of
      soluble receptors after release into the blood stream is maintained. We addressed
      this question by studying the function of the soluble IL-6R (sIL-6R) at the
      cellular level in the liver. We have generated double transgenic mice
      coexpressing human sIL-6R and human IL-6 in the liver and have analyzed the
      expression patterns by in situ hybridization. The expression of the human sIL-6R,
      driven by the phosphoenolpyruvate carboxykinase promoter, is located mainly in
      periportal areas, whereas human IL-6 under the control of the metallothionein
      promoter is uniformly expressed throughout the liver. We show here by in situ
      hybridization that acute phase protein gene expression induced by human IL-6 and
      human sIL-6R correlated with the periportal expression of sIL-6R, indicating that
      sIL-6R acts mainly in an area where it is generated. We conclude that in a
      concentration-dependent manner, at low concentrations of sIL-6R, there is a
      predominantly paracrine action at the site of its generation, whereas at higher
      concentrations of the sIL-6R there are both local and systemic effects.

PMID- 9233647
TI  - Recombinant guinea pig and human RANTES activate macrophages but not eosinophils
      in the guinea pig.
AB  - To characterize the biologic activities of potential mediators of allergic
      inflammation, we have cloned, expressed, and purified guinea pig RANTES
      (gpRANTES). cDNA for gpRANTES was cloned from Con A-stimulated guinea pig spleen
      cells. A high level of gpRANTES expression in Escherichia coli was achieved by
      mutation of a human RANTES (hRANTES) expression construct to obtain a 68-amino
      acid protein identical with the predicted guinea pig amino acid sequence,
      assuming an equivalent amino terminus as the human protein. Purified gpRANTES was
      an effective stimulus of human eosinophils as assessed by increases in
      intracellular free calcium in fura-2-loaded cells and chemotactic responses in
      vitro. gpRANTES exhibits similar potency and efficacy to hRANTES. In marked
      contrast, neither gpRANTES nor hRANTES was able to activate guinea pig peritoneal
      eosinophils in these assays, even in the presence of IL-5. However, gpRANTES was
      found to be a potent stimulator of guinea pig peritoneal macrophages. Following
      tracheal instillation of gpRANTES, a dose-dependent increase in macrophages, but
      not eosinophils, was observed in gpBAL. Macrophage accumulation was detectable by
      6 h and sustained for at least 48 h. These results indicate that RANTES in the
      guinea pig may have a different cellular selectivity than that described in the
      human, which may be important in the use of animal models in the analysis of
      allergic disorders. These selectivities do not appear to be accounted for by
      differences in guinea pig and human RANTES sequences.

PMID- 9233648
TI  - In vivo IL-12 administration induces profound but transient commitment to T
      helper cell type 1-associated patterns of cytokine and antibody production.
AB  - There is much interest in the utility of exogenous IL-12 as a biologic adjuvant
      in immediate hypersensitivity and infectious or parasitic diseases where the
      induction of Th1 responses is strongly associated with protective immunity. Using
      an immediate hypersensitivity model in which C57Bl/6 mice immunized with OVA
      (alum) normally generate Th2-dominated responses, we examined the ability of rIL
      12 to direct and maintain OVA-specific cytokine and Ab responses in a Th1
      direction. Exogenous IL-12 administered coincident with OVA immunization
      stimulated elevated serum IFN-gamma levels, enhanced IFN-gamma synthesis, and
      inhibited IL-4 synthesis in bulk culture; 80 to 99% inhibited primary Ag-specific
      serum IgE and IgG1 responses; and 15- to 20-fold enhanced IgG2a synthesis.
      However, each of these effects was highly transient, as exogenous IL-12, given at
      levels up to those associated with serious toxicity, failed to have a lasting
      impact on the OVA-specific T or B cell response. This transience was evident in
      primary bulk culture cytokine synthesis; in limiting dilution analysis of the
      frequency of OVA-specific IFN-gamma-, IL-4-, or IL-10-producing CD4 T cells; and,
      most importantly, in vivo effector responses such as IgE production to secondary
      and tertiary OVA immunization. The finding that the intense Th1-like phenomena
      seen following in vivo administration of rIL-12 with this exogenous Ag are highly
      transient and are not associated with alterations in the allergen-specific CD4 T
      cell repertoire to Th1-like patterns suggests a need for caution in the
      enthusiasm for the use of this cytokine as a biologic adjuvant.

PMID- 9233649
TI  - Structure-function analysis of the integrin beta 7 subunit: identification of
      domains involved in adhesion to MAdCAM-1.
AB  - Beta 7 integrins serve special roles in mucosal immunity. Alpha 4 beta 7-mediated
      adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs
      lymphocyte homing to the gut, and alpha E beta 7 mediates binding of lymphocytes
      to E-cadherin on epithelial cells. Since alpha 4 beta 7 mediates adhesion to
      MAdCAM-1 but alpha 4 beta 1 does not, we used beta 7/beta 1 chimeras to directly
      assess the importance of specific regions of beta 7 in MAdCAM-1 binding. We found
      a region of beta 7 (residues 46-386) that accounts for specificity of alpha 4
      beta 7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric beta
      7 subunits to map epitopes recognized by fifteen anti-beta 7 mAbs. Six of seven
      Abs that block adhesion to MAdCAM-1 and E-cadherin (Fib 21, 22, 27, 30, 504; Act
      1) mapped to amino acid residues 176-250. Residues 176-250 lie within the region
      of beta 7 that specifies MAdCAM-1 binding and also within a region that has a
      predicted structure homologous to the metal ion-dependent adhesion site (MIDAS)
      domains of the integrin subunits alpha L and alpha M. Three new Abs that
      recognize beta 7 in the presence of Mn2+, but not Ca2+, and promote adhesion to
      MAdCAM-1, mapped to amino acids 46-149. One blocking and five other Abs mapped to
      other regions (amino acids 387-725). We conclude that a MIDAS-like domain serves
      a critical role in beta 7 integrin-mediated adhesion.

PMID- 9233650
TI  - Expression of an anti-DNA-associated VH gene in immunized and autoimmune mice.
AB  - The J558 family BW-16 VH gene is closely associated with the autoimmune response
      to DNA of lupus-prone mice. We have followed the expression of VHBW-16-encoded
      heavy chains in cDNA libraries prepared from unmanipulated normal (C3H, AKR) and
      autoimmune (New Zealand Black/New Zealand White F1) mice, and from mice immunized
      with a highly immunogenic peptide/DNA complex. The prevalence, clonal
      heterogeneity, and structural properties (somatic mutation, complementarity
      determining region 3 composition) of these H chains were investigated, and the
      DNA affinity of VHBW-16-encoded hybridoma mAb was measured in solution. We find
      that H chains encoded by VHBW-16 are very rare in Igs of normal mice, but
      increase significantly in peptide/DNA-immunized mice, and dramatically in
      diseased mice. The experimentally induced VHBW-16-encoded H chains are clonally
      restricted, somatically mutated, partly switched from IgM to IgG, and give rise
      to anti-DNA Abs with low affinity. In contrast, the VHBW-16-encoded H chains from
      diseased New Zealand Black/New Zealand White mice are clonally heterogeneous,
      exclusively of the IgG isotype, and produce high affinity anti-DNA
      autoantibodies. We conclude that the experimentally induced and spontaneous
      immune responses to DNA are qualitatively similar, but quantitatively different,
      and may truly reflect the principles of self immunologic tolerance.

PMID- 9233651
TI  - Differential expression of cyclic nucleotide phosphodiesterase 3 and 4 activities
      in human T cell clones specific for myelin basic protein.
AB  - Little is known concerning the relative distribution and function of the
      different cyclic nucleotide phosphodiesterases (PDEs) in lymphocytes. Recent
      reports, however, have indicated that specific PDE4 inhibitors were effective in
      treatment of experimental allergic encephalomyelitis, an animal model of multiple
      sclerosis. The therapeutic effect of PDE4 inhibitors is thought to be related to
      inhibition of autoreactive CD4+ T cells specific for myelin basic protein (MBP)
      or other myelin proteins. Human autoreactive CD4+ T lymphocyte clones (TCC),
      specific for the immunodominant MBP epitope (amino acids 83-99), contain PDE3 and
      PDE4, two PDEs that exhibit a high affinity for cAMP. Amplification of TCC mRNA
      by reverse transcription-PCR indicated that TCC PDE3 mRNA was of the PDE3B, not
      PDE3A, subtype. Different TCC contained different proportions of PDE3 and PDE4,
      and their activities increased during Ag (MBP) stimulation. Specific PDE3
      (cilostamide) and PDE4 (rolipram) inhibitors suppressed [3H]thymidine
      incorporation in TCC. Since it is believed that many autoimmune diseases are at
      least partially mediated by autoreactive CD4+ T cells, these observations may
      have important implications not only for the treatment of multiple sclerosis but
      also for other autoimmune diseases.

PMID- 9233652
TI  - Characterization of thyroglobulin-directed and polyreactive catalytic antibodies
      in autoimmune disease.
AB  - Polyreactive and thyroglobulin (Tg)-directed proteolytic activities present in
      the serum IgG of healthy controls and patients with autoimmune disease were
      studied by electrophoretic separation of 125I-labeled Tg reaction products and
      spectrofluorometric measurement of Pro-Phe-Arg-methylcoumarinamide cleavage at
      the Arg-methylcoumarinamide bond. A decrease of the polyreactive proteolytic
      activity accompanying an increase of the Tg-cleaving activity in IgG from
      autoimmune thyroiditis (ATh) and systemic lupus erythematosus (SLE) patients was
      evident. The Tg, a known target of autoimmune reactions in ATh, was cleaved at
      lower levels by Abs from patients with this disease than from SLE patients. The
      Tg-cleaving and Tg-binding activities of the autoantibody preparations were not
      correlated. Enhanced rates of cleavage at saturating substrate concentrations
      (Vmax), not increased Tg-binding affinities, were evident in IgG preparations
      with the greatest Tg-cleaving activity. Similarly, diminution of the polyreactive
      proteolytic activity in IgG from the autoimmune disease patients was due to
      decreased Vmax values, not decreased substrate-binding affinities. No cleavage of
      Tg by IgG from subjects with HIV-1 infection, or from mice hyperimmunized with an
      albumin-hapten conjugate was evident, suggesting that generation of Tg-cleaving
      Abs does not accompany V region affinity maturation in response to unrelated Ags.
      These observations establish Tg as a target of catalytic autoantibodies in SLE
      and ATh, suggest a transition from polyreactive proteolytic activity to
      autoantigen-directed activity in autoimmune disease, and open the possibility
      that combining site chemical reactivity is a factor driving the expression of
      catalytic activity by autoantibodies.

PMID- 9233654
TI  - Bispecific humanized anti-IL-2 receptor alpha beta antibodies inhibitory for both
      IL-2- and IL-15-mediated proliferation.
AB  - Humanized anti-Tac (HAT) and Mik beta1 (HuMik beta 1) Abs directed at IL-2R alpha
      and IL-2R beta, respectively, inhibit IL-2 binding and biological activity and
      together act synergistically in vitro. The Abs have been used successfully in
      primate models of allograft rejection, graft-vs-host disease, and autoimmunity.
      We produced bifunctional humanized anti-IL-2R alpha beta Abs (BF-IgG) to combine
      the specificity of the two Abs into one entity by fusing HAT-producing NSO cells
      and HuMik beta 1-producing Sp2/0 cells. BF-IgG was purified using protein G
      Sepharose affinity chromatography, followed by IL-2R alpha and IL-2R beta
      affinity chromatography and hydrophobic interaction chromatography. BF-IgG
      exhibited both anti-IL-2R alpha and anti-IL-2R beta specificities in binding
      assays. While the Ab binds the IL-2R with intermediate affinity (Kd = 2.82 nM),
      it does not inhibit IL-15 binding to its high affinity IL-15R. In Kit225/K6 (IL
      2R alpha beta gamma+) cells, BF-IgG was 10-fold more potent than a HAT/HuMik beta
      1 equimolar mixture in blocking IL-2-induced proliferation and, unexpectedly, was
      at least 65-fold more active than the mixture in blocking IL-15-induced
      proliferation. This dual inhibitory activity may be due to cross-linking of the
      IL-2R alpha and IL-2R beta, thus blocking IL-2 binding and possibly impeding the
      association of IL-2R beta with IL-15R. BF-IgG has potent immunosuppressant
      activities against both IL-2- and IL-15-mediated responses, and this antagonist
      could be more efficacious than HAT and/or HuMik beta 1 for the treatment of
      autoimmunity and the prevention of allograft rejection.

PMID- 9233653
TI  - Requirement of IL-4 and liver NK1+ T cells for concanavalin A-induced hepatic
      injury in mice.
AB  - Con A-induced hepatic injury of mice accompanied by elevated transaminase was
      inhibited after in vivo depletion of liver NK cells and NK1+ T cells with
      intermediate TCR by anti-NK1 Ab or anti-IL-2Rbeta Ab. However, depletion of liver
      NK cells alone by anti-asialo-GM1 Ab did not inhibit hepatic injury. Although
      depletion of NK1+ T cells inhibited Con A-induced IL-2R expression of CD4+ high
      TCR (TCRhigh) cells and IL-4 mRNA expression of hepatic mononuclear cells,
      exogenous IL-4 engendered Con A-induced hepatic injury and endowed the expression
      of IL-2R of CD4+ TCRhigh cells. It was also found that in vivo treatment with
      anti-IL-4 Ab before Con A administration inhibited Con A-induced hepatic injury.
      In addition, although Con A did not induce hepatic injury in MHC class I
      deficient mice, exogenous IL-4 again engendered severe hepatic injury in these
      mice. Further, while serum TNF-alpha levels induced by Con A were greatly
      decreased in NK1+ T cell-depleted mice and class I-deficient mice, TNF-alpha
      levels were recovered by exogenous IL-4. These findings reveal that although CD4+
      TCRhigh cells in the liver and their production of TNF-alpha are the direct
      effectors of Con A-induced hepatic injury, liver NK1+ T cells also play an
      important role in this hepatitis model. Con A hepatitis may serve as an
      experimental model for human autoimmune hepatitis.

PMID- 9233655
TI  - Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on
      normal B cell subpopulations and decreased levels during the development of
      autoimmunity in MRL/lpr mice.
AB  - Human complement receptors type 1 (hCR1;CD35) and type 2 (hCR2;CD21) are
      expressed on B lymphocytes at specific stages during differentiation and
      activation. These receptors play critical roles in the immune response to T
      dependent Ags in addition to germinal center formation. Expression of both hCR2
      and hCR1 is decreased on B lymphocytes of patients with systemic lupus
      erythematosus (SLE). We have studied the expression of mouse CR2 and CR1 on
      normal populations of mouse B lymphocytes in BALB/c mice. Our results demonstrate
      that expression of these receptors in the normal state closely parallels that of
      hCR2. During bone marrow development, expression is first detected on low
      B220/high IgM cells, demonstrating that complement receptors appear after central
      tolerance mechanisms are completed. In the splenic microenvironment the highest
      levels of receptor expression are found on marginal zone B lymphocytes. Mouse CR2
      and CR1 are also found on peritoneal B1a and B1b cells in addition to IgA+
      Peyer's patch B cells. Activation of splenic B cells under Th2 conditions results
      in a marked decrease in receptor expression. To determine whether the patterns of
      receptor expression also parallel those found in human disease, we studied the
      MRL lpr/lpr (MRL/lpr) model of SLE. Interestingly, we found an early decrease in
      complement receptor expression that is progressive and first detectable before
      major clinical manifestations of nephritis. We hypothesize that the early
      decrease in complement receptor expression such as that demonstrated by MRL/lpr
      mice plays an important role in the pathogenesis of murine and perhaps human SLE.

PMID- 9233656
TI  - A 17-Mer self-peptide of acetylcholine receptor binds to B cell MHC class II,
      activates helper T cells, and stimulates autoantibody production and
      electrophysiologic signs of myasthenia gravis.
AB  - We have identified in an extracellular segment of the alpha1 subunit of nicotinic
      acetylcholine receptor (AChR) of homologous muscle a 17-residue autoantigen that,
      without conjugation to a carrier, activates Th lymphocytes and induces production
      of autoantibodies that cause electrophysiologic signs of experimental autoimmune
      myasthenia gravis. A panel of overlapping synthetic peptides revealed two T cell
      epitopes, one encompassed by residues 121-136 and the other by 129-145. Residues
      129 (glutamic acid) and 130 (isoleucine) were implicated in a pathogenic B cell
      epitope. Peptide 129-145 (Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Glu-Gln-Asn-Cys
      Ser-Met-Lys, a conserved sequence in rat and human AChR) induced autoantibody
      production in 76% of rats. All seropositive rats had evidence of experimental
      autoimmune myasthenia gravis; five of five tested had electrophysiologic signs,
      and all had loss of immunochemically measured autologous muscle AChR. Analogues
      of 129-145, with single residues substituted by alanine, revealed phenylalanine
      135, phenylalanine 137, and glutamic acid 139 as most important determinants of
      Ag/MHC-II/TCR interactions; phenylalanine 137 is critical for T cell activation.
      B cells were the major MHC-II-positive cell type to which the self-peptide 129
      145 bound in a population of nonimmune splenic cells. More efficient processing
      and presentation of the Th cell epitope by an expanded population of immune B
      cells selected by specifically binding another epitope of the same peptide would
      greatly amplify the production of autoantibodies. Peptide autoantigens of this
      type could plausibly perpetuate the autoantibody response in myasthenia gravis,
      and are a rational target for strategies aimed at Ag-specific therapeutic
      intervention.

PMID- 9233657
TI  - Invasion and cytopathic killing of human lymphocytes by spirochetes causing Lyme
      disease.
AB  - Lyme disease is a persistent low-density spirochetosis caused by Borrelia
      burgdorferi sensu lato. Although spirochetes causing Lyme disease are highly
      immunogenic in experimental models, the onset of specific antibody responses to
      infection is often delayed or undetectable in some patients. The properties and
      mechanisms mediating such immune avoidance remain obscure. To examine the nature
      and consequences of interactions between Lyme disease spirochetes and immune
      effector cells, we coincubated B. burgdorferi with primary and cultured human
      leukocytes. We found that B. burgdorferi actively attaches to, invades, and kills
      human B and T lymphocytes. Significant killing began within 1 hour of mixing.
      Cytopathic effects varied with respect to host cell lineage and the species,
      viability, and degree of attenuation of the spirochetes. Both spirochetal
      virulence and lymphocytic susceptibility could be phenotypically selected, thus
      indicating that both bacterial and host cell factors contribute to such
      interactions. These results suggest that invasion and lysis of lymphocytes may
      constitute previously unrecognized factors in Lyme disease and bacterial
      pathogenesis.

PMID- 9233659
TI  - Pathological manifestations in murine Lyme disease: association with tissue
      invasion and spirochete persistence.
AB  - The clinical manifestations of human Lyme disease present with a spectrum of
      tissue or organ involvement and severity of symptoms. The murine model of Lyme
      disease has proved to be an accurate reflection of many of the human symptoms of
      disease and has been particularly useful for studying development of subacute
      arthritis and tendonitis. Direct tissue invasion by Borrelia burgdorferi and
      persistence of high levels of spirochetes in tissues are important components of
      arthritis development. The outer-surface lipoproteins contain a biologically
      active lipid-modified moiety with potent ability to stimulate inflammatory
      cytokine production and other inflammatory mediators such as nitric oxide.
      Localized inflammation stimulated by these lipoproteins may be the trigger for
      neutrophil infiltration, synovial proliferation, and other events associated with
      this arthritis. Invasion of maternal uterine tissue, but not direct invasion of
      fetal tissue, is associated with low levels of pregnancy loss in mice infected
      during gestation, consistent with the detrimental effect of inflammatory
      cytokines on pregnancy.

PMID- 9233658
TI  - Protective and arthritis-resolving activity in sera of mice infected with
      Borrelia burgdorferi.
AB  - Transfer of immune serum from immunocompetent mice infected with B. burgdorferi
      protects mice against syringe challenge, and transfer of immune serum after
      infection is established induces arthritis resolution but does not clear
      infection or spirochetemia or resolve carditis. Immune serum had very-high-titer
      passive protective activity against syringe challenge but failed to protect mice
      against host-adapted spirochetes when they were challenged with infected tissue
      transplants. Mice were passively immunized at selected intervals relative to
      challenge inoculation with antisera to recombinant forms of an immunodominant
      region of flagellin, P39, and OspC (which are recognized by immune serum), but
      none provided protection or modified existing infection or disease. Results
      suggest that spirochetes within joints, but not in other tissues, are selectively
      vulnerable to immune serum and that immune serum appears to contain antibody
      against yet-to-be-identified antigens that may be selectively expressed in the
      context of joint tissue.

PMID- 9233660
TI  - Activity of sera from patients with Lyme disease against Borrelia burgdorferi.
AB  - Sera from patients with Lyme disease were evaluated for their ability to kill
      Borrelia burgdorferi in vivo and in vitro. Separate groups of C3H mice received
      sera from seropositive humans with early- or late-stage Lyme disease or from
      seronegative controls. Eighteen to 24 hours after passive transfer of sera, the
      mice were challenged with 100,000 low-passage B. burgdorferi strain B31 or CA287
      organisms. Sera from subjects with late-stage Lyme disease protected the mice
      against infection after challenge with B. burgdorferi, but sera from subjects
      with early-stage Lyme disease were not protective. Late-stage sera also inhibited
      the growth of B. burgdorferi in microcultures on Barbour-Stoenner-Kelly media
      better than early-stage sera. Immunoblot analysis revealed that the protective
      properties of late-stage sera were associated with a response of antibodies to
      multiple proteins. This response included strong reactivity with the outer
      surface proteins A and B, which was lacking in early-stage sera.

PMID- 9233661
TI  - The western immunoblot for Lyme disease: determination of sensitivity,
      specificity, and interpretive criteria with use of commercially available
      performance panels.
AB  - Recent recommendations for the serological diagnosis of Lyme disease include
      statements on quality assurance and the use of performance panels to assess
      laboratory competency. We used two performance panels--one from the Centers for
      Disease Control and Prevention (CDC) and one from Boston Biomedica Inc. (West
      Bridgewater, MA)-to evaluate the sensitivity and specificity of four western blot
      kits. We used the same panels to compare the interpretive criteria for western
      blots as proposed by participants in the Centers for Disease Control and
      Prevention, Association of State and Territorial Public Health Laboratory
      Directors Conference and those proposed by BBI Clinical Laboratories (BBICL; New
      Britain, CT). Our results indicated that the BBICL western blots were more
      sensitive than those of the CDC, MarDx (Carlsbad, CA), or Cambridge Biotech
      (Rockville, MD). However, use of the CDC criteria with the BBICL western blots
      increased specificity to 100% but reduced sensitivity to 74.3%. A sample table is
      provided as an example of the test results obtained with the BBI performance
      panel. Obviously, this work should be confirmed by other investigators.

PMID- 9233662
TI  - The cold zone: a curious convergence of tick-transmitted diseases.
AB  - In recent years, investigators have gained an increasing appreciation of the
      complexity of the Lyme disease transmission cycle with regard to the number of
      pathogens involved. Babesia microti, a blood parasite that is related to the
      organism that causes malaria, frequently accompanies the Lyme disease spirochete
      in the mouse reservoir. Recently, a newly described Ehrlichia species related to
      Ehrlichia equi has been found to be transmitted by the deer tick. Human
      infections with these agents alone and in combination are now being described,
      and the successful treatment of these infections may depend on proper diagnosis.
      The convergence of these and other organisms on the Lyme disease transmission
      cycle provides a unique opportunity to study pathogen-pathogen interactions in a
      naturally occurring model.

PMID- 9233663
TI  - Is human granulocytic ehrlichiosis a new Lyme disease? Review and comparison of
      clinical, laboratory, epidemiological, and some biological features.
AB  - Human granulocytic ehrlichiosis (HGE) and Lyme disease are caused by infectious
      agents transmitted by deer ticks (Ixodes scapularis). Because of the shared tick
      vector and increased seroprevalence of HGE in patients with Lyme disease, there
      is some confusion about the identity of these infectious agents and the
      clinicopathologic spectrum of the disease. HGE is an acute febrile illness
      associated with leukopenia, thrombocytopenia, and increased serum activities of
      hepatic transaminases. In contrast, Lyme disease is most often subacute, with the
      frequent presence of erythema migrans rash and infrequent leukopenia,
      thrombocytopenia, or elevated serum hepatic transaminase activities. Some
      ehrlichia infections in animals and humans may become persistent, and Ehrlichia
      mediated defects in host defense and immune suppression can allow secondary and
      opportunistic infections. Because of these properties of Ehrlichia species, their
      role in modifying the clinical course of Lyme disease may be hypothesized and
      should be tested.

PMID- 9233664
TI  - The antimicrobial agent melittin exhibits powerful in vitro inhibitory effects on
      the Lyme disease spirochete.
AB  - Borrelia burgdorferi has demonstrated a capacity to resist the in vitro effects
      of powerful eukaryotic and prokaryotic metabolic inhibitors. However, treatment
      of laboratory cultures on Barbour-Stoenner-Kelly medium with melittin, a 26-amino
      acid peptide contained in honeybee venom, showed immediate and profound
      inhibitory effects when they were monitored by dark-field microscopy, field
      emission scanning electron microscopy, and optical density measurements.
      Furthermore, at melittin concentrations as low as 100 microg/mL, virtually all
      spirochete motility ceased within seconds of inhibitor addition. Ultrastructural
      examination of these spirochetes by scanning electron microscopy revealed obvious
      alterations in the surface envelope of the spirochetes. The extraordinary
      sensitivity of B. burgdorferi to mellitin may provide both a research reagent
      useful in the study of selective permeability in microorganisms and important
      clues to the development of effective new drugs against lyme disease.

PMID- 9233665
TI  - Tetracycline therapy for chronic Lyme disease.
AB  - Two hundred seventy-seven patients with chronic Lyme disease were treated with
      tetracycline for 1 to 11 months (mean, 4 months); the outcomes for these patients
      were generally good. Overall, 20% of the patients were cured; 70% of the
      patients' conditions improved, and treatment failed for 10% of the patients.
      Improvement frequently did not take place for several weeks; after 2 months of
      treatment, 33% of the patients' conditions were significantly improved (degree of
      improvement, 75%-100%), and after 3 months of treatment, 61% of the patients'
      conditions were significantly improved. Treatment outcomes for seronegative
      patients (20% of all patients) were similar to those for seropositive patients.
      Western immunoblotting showed reactions to one or more Borrelia burgdorferi
      specific proteins for 65% of the patients for whom enzyme-linked immunosorbent
      assays were negative. Whereas age, sex, and prior erythema migrans were not
      correlated with better or worse treatment outcomes, a history of longer duration
      of symptoms or antibiotic treatment was associated with longer treatment times to
      achieve improvement and cure. These results support the use of longer courses of
      treatment in the management of patients with chronic Lyme disease. Controlled
      trials need to be conducted to validate these observations.

PMID- 9233666
TI  - Functional brain imaging and neuropsychological testing in Lyme disease.
AB  - Differentiating neuropsychiatric Lyme disease from a primary psychiatric disorder
      can be a daunting task. This article describes how functional brain imaging and
      neuropsychological testing can be particularly valuable in helping to make
      diagnostic distinctions. In addition to a review of the relevance of functional
      imaging to neuropsychiatry in general, recent findings are presented regarding
      the use of single photon emission computed tomographic (SPECT) imaging in Lyme
      disease.

PMID- 9233667
TI  - Why is chronic Lyme borreliosis chronic?
AB  - Chronic Lyme borreliosis (CLB) can present not only in different organs but also
      in different patterns. Although many theories exist about the mechanisms leading
      to CLB, it is known that viable Borrelia burgdorferi can persist for decades and
      cause late skin manifestations of acrodermatitis chronica atrophicans (ACA).
      Thus, the immunopathogenetic findings in ACA can serve as a model for studying
      the chronic course of Lyme borreliosis. Recent findings indicate that the most
      important cell for antigen presentation, the epidermal Langerhans cell (LC), is
      invaded by B. burgdorferi in early Lyme borreliosis. Therefore, LCs were stained
      immunohistochemically with different markers to investigate their functional
      activity. Numbers of CD1a+ LCs were reduced in erythema migrans but normal or
      slightly elevated in ACA. In both diseases there was also a marked downregulation
      of major histocompatibility complex class II molecules on LCs, as measured by
      staining of human leukocyte antigen DR. This phenomenon might be a mechanism that
      protects against the presentation of autoantigens and may be the cause of the
      impaired capacity of LCs to eliminate B. burgdorferi antigens, thus explaining
      why CLB is chronic.

PMID- 9233668
TI  - Specific issues in the design and implementation of an efficacy trial for a Lyme
      disease vaccine.
AB  - Lyme disease is an emerging infection that has now become the most commonly
      reported vector-borne disease in the United States. In the 20 years since its
      initial description, scientific and technological advances have led to candidate
      vaccines for the prevention of Lyme disease. Recombinant outer surface protein A
      (OspA) vaccines have been successful in protecting mice in tick-challenge
      experiments. A candidate OspA vaccine has been found to be safe and immunogenic
      in phase I and II studies. This article describes some of the lessons that were
      learned and some of the unique obstacles encountered in the design and
      implementation of a large phase III efficacy field trial. Pivotal trials of
      vaccines for Lyme disease can be a major investment of time and resources for
      subjects, investigators, and sponsors. If properly conducted, they also present
      unique opportunities to expand our knowledge of the disease.

PMID- 9233669
TI  - Evidence for distinct prototype sequences within the Plasmodium falciparum Pf60
      multigene family.
AB  - Using oligonucleotides derived from Pf60.1, a member of the Plasmodium falciparum
      Pf60 multigene family, numerous fragments were amplified from genomic and cDNA
      from the 3D7 P. falciparum clone. DNA sequencing showed that the various
      fragments presented considerable diversity, indicating that the 3D7 repertoire
      contains at least 20 distinct versions of the region analysed. The various
      sequences aligned with either of two prototype sequences. Characteristic of the A
      type was the presence of a 21 bp motif, present in variable copy number, as well
      as a sequence homologous to the Babesia sp. RAP-1 consensus. The B prototype
      sequence did not present such features and substantially differed from the A
      type, due to accumulation of point mutations and numerous triplet deletions.
      Consistent with the marked differences between both sub-families, individual
      members from each sub-family did not cross-hybridise, produced distinct multiple
      band patterns on Southern blots and distinct chromosome profiles. Numerous hybrid
      sequences were observed. Interestingly, most var genes and var-related unspliced
      cDNAs described so far are of A/B hybrid type. These data suggest that the family
      has evolved by successive amplifications from two ancestral copies, with
      accumulation of mutations, as well as recombination and/or gene conversion
      events.

PMID- 9233670
TI  - Characterization of macromolecular transport pathways in malaria-infected
      erythrocytes.
AB  - We have previously provided evidence for a pathway in Plasmodium falciparum
      infected erythrocytes, coined the parasitophorous duct pathway, which provides
      serum (macro)molecules direct access to intraerythrocytic parasites . The present
      study addresses the purity of the fluorescent macromolecules used to define the
      duct pathway and provides ultrastructural evidence for its presence. The
      fluorescent tracers used to characterize transport remain intact during their
      incubation with infected erythrocytes. Transport of macromolecules in the
      external medium or host cell cytosol to the intracellular parasites is shown to
      occur by two distinct pathways. Fluorescent dextrans in the erythrocyte cytosol
      are ingested by the parasite via a specialized organelle, the cytostome, and are
      transported to the parasite food vacuole. Transport through this pathway occurs
      throughout the asexual life cycle. By contrast, fluorescent dextrans in the
      external medium bypass the erythrocyte cytosol, and are internalized by the
      parasite by a process resembling fluid-phase endocytosis. Serial sections of
      mature parasites fixed and stained by various methods for transmission electron
      microscopy reveal areas of apparent membrane continuity between the erythrocyte
      membrane and the parasitophorous vacuolar membrane that surrounds the parasite,
      that could leave the parasites exposed to the external medium. Using carboxylate
      and amidine-modified fluorescent latex spheres and laser scanning confocal
      microscopy, macromolecules up to 50-70 nm in diameter are found to have direct
      access to intraerythrocytic parasites. This size exclusion is consistent with the
      dimensions of the parasitophorous duct pathway revealed by electron microscopy.
      This investigation reports for the first time the existence of two, distinct
      macromolecular transport pathways in malaria-infected erythrocytes.

PMID- 9233671
TI  - Surprising diversity and distribution of spliced leader RNAs in flatworms.
AB  - Trans-splicing generates the mature 5' ends of certain mRNAs through the addition
      of a small spliced leader (SL) exon to pre-mRNAs. To search for novel flatworm
      spliced leaders, degenerate oligonucleotides and 5' RACE [corrected was used to
      isolate and characterize the 5' terminal sequences of enolase mRNAs in diverse
      flatworms. Several new spliced leaders and their SL RNA genes were identified,
      characterized, and compared. All parasitic trematodes examined trans-splice
      enolase. A primitive polyclad turbellarian, Stylochus zebra, also contains a
      trans-spliced enolase mRNA. The S. zebra SL is the longest SL yet identified, 51
      nucleotides. Comparison of flatworm SLs indicates that they vary significantly in
      sequence and length. This suggests that neither spliced leader exon sequence nor
      size is likely to be essential for trans-splicing in flatworms. Flatworm SL RNAs
      have unusual Sm binding sites with characteristics distinct from other known
      flatworm snRNA Sm binding sites. Predicted flatworm SL RNA secondary structures
      show variation exhibiting 2-4 stem loops. Although limited in sequence
      similarity, phylogenetically conserved regions within the diverse flatworm SL
      RNAs suggest that they are likely to be derived from a common ancestor and
      provide information on potentially important SL RNA elements. The identification
      of a SL in a primitive flatworm suggests that trans-splicing may have been an
      ancestral feature in the phylum. Representative species of other early and more
      recent clades within the phylum, however, do not trans-splice enolase, nor do
      they or representatives of several other flatworm groups, have an SL RNA with a
      phylogenetically conserved region identified in the current study.

PMID- 9233672
TI  - The chromosomal organization of the Plasmodium falciparum var gene family is
      conserved.
AB  - The var gene family of Plasmodium falciparum encodes the protein PfEMP1 which is
      located on the surface of infected erythrocytes and is the receptor that mediates
      binding to ligands on endothelial cells. This family of proteins is responsible
      for antigenic variation and differences in binding phenotype to ligands such as
      CD36 and ICAM1. We have compared the organization of the var gene family in three
      in vitro cloned lines of P. falciparum and show that most var genes are located
      in the subtelomeric region of each chromosome closely linked to the repetitive
      sequence rep20. While most chromosomes possess var genes in the subtelomeric
      region, in each in vitro cloned line there are some chromosomes that have deleted
      subtelomeric repetitive regions which include var genes. Comparison of the
      location of var genes in a field isolate showed that it does not have any
      detectable subtelomeric deletions as all chromosomes contain var genes and rep20
      sequences. We have detected three chromosomes (4, 7 and 12) that contain var gene
      loci in more stable central regions and the position of these genes on chromosome
      4 in the cloned lines analysed is conserved. The location of most of the var gene
      family in the subtelomeric region of the genome of P. falciparum has important
      implications for the generation of antigenic diversity of the PfEMP1 protein.

PMID- 9233674
TI  - The mitochondrion in dividing Leishmania tarentolae cells is symmetric and
      circular and becomes a single asymmetric tubule in non-dividing cells due to
      division of the kinetoplast portion.
AB  - Kinetoplastid protozoa have a single mitochondrion that extends throughout the
      cell. The disk-shaped portion of the mitochondrion adjacent to the basal body of
      the flagellum contains the kinetoplast DNA nucleoid body which consists of
      thousands of catenated minicircles and a smaller number of catenated maxicircles.
      The maxicircles contain structural genes and cryptogenes, rRNA genes, and a few
      guide RNA genes The minicircles contain the majority of the guide RNA genes. The
      long slender non-dividing stationary phase Leishmania tarentolae cells in culture
      have an asymmetric mitochondrion that consists of a single tubule extending from
      one edge of the kinetoplast portion. This presents a problem for cell division,
      in that one daughter cell will receive significantly less mitochondrial membranes
      than the other cell. We show in this paper that the solution to this problem is
      that dividing cells, which are normally shorter and rounder than stationary phase
      cells, possess a symmetric circular mitochondrion that has mitochondrial tubules
      extending from both edges of the kinetoplast which are joined in the posterior
      region of the cell. This implies that growth of the mitochondrion occurs after
      cell division, either from elongation of the longitudinal tubule towards the
      anterior of the cell, or from elongation of the kinetoplast portion of the
      mitochondrion towards the posterior region and fusion of the tubules.

PMID- 9233673
TI  - Prenylation of proteins in Trypanosoma brucei.
AB  - Prenyl modification of proteins by farnesyl and geranylgeranyl isoprenoids occurs
      in a variety of eukaryotic cells. Culturing of Trypanosoma brucei in the presence
      of [3H]mevalonolactone (which is hydrolyzed in cells to give mevalonic acid, the
      precursor of protein prenyl groups) and an inhibitor of mevalonic acid
      biosynthesis leads to the radiolabeling of a specific set of proteins when
      analyzed by gel electrophoresis. T. brucei proteins were also labeled when cells
      were cultured in the presence of [3H]farnesol or [3H]geranylgeraniol, and each
      prenol labels a distinct set of proteins. Unlike mammalian cells, only a few T.
      brucei proteins of molecular weights similar to those of the mammalian Ras
      superfamily of GTPase (20-30 kDa) were labeled with [3H]farnesol or
      [3H]geranylgeraniol. When the 0-55% ammonium sulfate fraction of T. brucei
      cytosol was fractionated on anion exchange chromatography, protein
      farnesyltransferase (PFT) and protein geranylgeranyltransferase-I (PGGT-I)
      activities were detected and elute as two distinct peaks. Partially purified T.
      brucei PFT and PGGT-I display partly different specificities toward prenyl
      acceptor substrates from those of mammalian protein prenyltransferases. As shown
      previously, rat PFT utilizes proteins ending in CVLS and CVIM as efficient prenyl
      acceptors and rat PGGT-I utilizes proteins ending in CVLL and CVIM in vitro. On
      the contrary, T. brucei PFT farnesylates a protein ending in CVIM but not CVLS or
      CVLL, and T. brucei PGGT-I preferentially geranylgeranylates a protein ending in
      CVLL.

PMID- 9233675
TI  - Extensive genetic diversity in Blastocystis hominis.
AB  - Blastocystis homonis is a common human parasite of uncertain role in human
      disease. Approximately equal numbers of reports implicate it and exonerate it as
      a pathogen. Genetic diversity in B. hominis was investigated using riboprinting
      to study sequence variation in the small subunit ribosomal RNA genes of 30
      randomly selected isolates. Extensive sequence variation was discovered in B.
      hominis ribosomal RNA genes and this species consists of at least seven
      morphologically identical but genetically quite distinct organisms. If only a
      subset of the B. hominis variants have the potential to cause disease in humans
      this might explain the disparate findings reported. Future clinical studies must
      take the heterogeneity of B. hominis into account.

PMID- 9233677
TI  - Minimal variation in the Pfs28 ookinete antigen from Philippine field isolates of
      Plasmodium falciparum.

PMID- 9233676
TI  - Differentially expressed, abundant trans-spliced cDNAs from larval Brugia malayi.
AB  - Isolation and cloning of abundant reverse transcriptase-polymerase chain reaction
      (RT-PCR) products from the filarial nematode Brugia malayi using the conserved
      nematode spliced leader sequence and poly A as amplification targets has allowed
      us to identify abundant, stage specific transcripts from infective and post
      infective larvae. The predicted protein products of the most prominent full
      length transcripts from mosquito-derived L3 parasites are: (i) Bm-ALT-1, a
      homologue of a Dirofilaria immitis abundant larval protein: (ii) Bm-CPI-1, a
      cystatin-type cysteine protease inhibitor; (iii) Bm-ALT-3, a novel predicted 6
      kDa glycine/tyrosine-rich protein; and (iv) Bm-TPH-1, a homologue of a mammalian
      translationally-controlled tumour protein. Some transcripts were not full-length
      but had mis-primed at A-rich stretches of coding sequence: the most abundant of
      these was Bm-col-3, a which encodes a collagen homologous to Bp-COL-1 of Brugia
      pahangi. Similar analysis of abundant spliced leader (SL)/oligo-dT products from
      fourth-stage larvae 9 days post-infection yielded two dominant transcripts: (i)
      Bm-cdd-1, which encodes a protein with homology to cytidine deaminase, differing
      at only one amino acid position from its homologue described in Brugia pahangi;
      and (ii) the same truncated form of Bm-col-3 found in L3 preparations. Expression
      of the major transcripts was assessed by PCR amplification of cDNA libraries
      derived from each stage of the life cycle. alt1, alt-3 and cpi-1 were all found
      to be specific to the L3 stage, while cdd-1 was found only in the L4 cDNA
      library. Expression of these larval-specific transcripts was not detected in
      either microfilarial or adult libraries.

PMID- 9233678
TI  - A gene homologous to hgl2 of Entamoeba histolytica is present and expressed in
      Entamoeba dispar.

PMID- 9233679
TI  - Comparison of Plasmodium yoelii ookinete surface antigens with human and avian
      malaria parasite homologues reveals two highly conserved regions.

PMID- 9233680
TI  - Polymerase chain reaction-based gene disruption in Trypanosoma brucei.

PMID- 9233681
TI  - Characterization of an ATP-binding cassette transporter in Cryptosporidium
      parvum.

PMID- 9233682
TI  - An affinity column for phospholipase A2 based on immobilised
      acylaminophospholipid analogues.
AB  - A synthetic route was developed to prepare 2-acylamino phospholipid analogues
      suitable for immobilisation. The inhibitors, synthesised in either the (R)- and
      (S)-configuration, carried an omega-carboxyl group in one acyl chain for
      immobilisation to the matrix. As a matrix Sepharose 6B, derivatised with a polar,
      non-charged 16 atom spacer was used. Low-molecular weight phospholipase A2 binds
      in a calcium-dependent way to the immobilised (S)-inhibitor and not to the
      immobilised (R)-inhibitor which shows that binding involves specific active site
      interactions rather than hydrophobic chromatography. The specificity was further
      demonstrated by the fact that the immobilised (S)-inhibitor binds porcine
      pancreatic and snake venom phospholipases A2, but not the porcine pancreatic
      zymogen. Moreover, a mutant porcine pancreatic phospholipase A2 in which the
      active side residue His48 has been replaced by Gln, was not bound by the column.
      This column material might be applicable for affinity purification of
      phospholipase A2 and for screening of phage display libraries.

PMID- 9233683
TI  - The high-affinity quinacrine binding site is located at a non-annular lipid
      domain of the nicotinic acetylcholine receptor.
AB  - This work deals with the localization of the high-affinity non-competitive
      quinacrine binding site on the muscle-type nicotinic acetylcholine receptor
      (AChR). Specifically, quantitative steady-state fluorescence spectroscopy is used
      to determine whether quinacrine binds to a site located at either the annular or
      the non-annular lipid domain. For this purpose, we measure the ability of spin
      labelled phosphatidylcholine (SL-PC) to quench AChR-bound quinacrine, AChR-bound
      ethidium and membrane-partitioned 7-(9-anthroyloxy)stearate (7-AS) fluorescence.
      Additionally, we compare the accessibility of SL-PC which is considered to bind
      only to the annular lipid domain of the AChR with the accessibility of two non
      annular domain-sensing lipids such as 5-doxylstearate (5-SAL) and spin-labelled
      androstane (ASL). Initial experiments using 7-AS established the experimental
      conditions for maximum SL-PC membrane partitioning. The non-specific quenching
      elicited by increasing turbidity of the sample after addition of SL-PC is
      corrected by means of parallel experiments with unlabelled egg yolk
      phosphatidylcholine. After correction, the SL-PC quenching experiments show the
      following order in quenching efficiency: 7-AS > quinacrine >> ethidium. The
      relative intrinsic sensitivity of quinacrine to TEMPO paramagnetic quenching in
      acetonitrile is considered to be approximately two times higher than that for 7
      AS. Thus, SL-PC was found to be more accessible (about 5-fold) to the membrane
      partitioned 7-AS than to the quinacrine locus. In addition, SL-PC was virtually
      not accessible to the high-affinity non-luminal binding site for ethidium. The
      relative capacity of SL-PC, 5-SAL, and ASL to quench AChR-bound quinacrine
      fluorescence indicated that the spin-labelled lipid accessibility to the
      quinacrine binding site follows the order: 5-SAL > ASL >> SL-PC. Examination of
      the effect of high concentrations of 5-SAL, of its unlabelled parent stearate,
      and of SL-PC on ethidium and quinacrine binding showed that: (a) both fatty acids
      displace quinacrine, but not ethidium, from its high-affinity binding site,
      however (b) 5-SAL was found to be more effective than stearate to displace
      quinacrine from its locus, whereas (c) SL-PC competes neither for the ethidium
      locus nor for the quinacrine binding site. The results suggest that the high
      affinity binding site for quinacrine is located at a non-annular lipid domain of
      the AChR. This particular area has been considered to be located at the
      intramolecular interfaces of the five AChR subunits and/or at the interstices of
      the transmembrane domains.

PMID- 9233684
TI  - Analysis of lipid metabolism in adipocytes using a fluorescent fatty acid
      derivative. I. Insulin stimulation of lipogenesis.
AB  - Stimulation of lipid synthesis (lipogenesis) is one of the most pronounced
      metabolic actions of insulin. Here we demonstrate insulin-stimulated lipogenesis
      in isolated rat adipocytes using a fatty acid derivative which carries a
      fluorophore. Three major fluorescent lipid products (lipids 1, 2, 3) are
      generated as revealed by TLC analysis and subsequent fluorescent scanning or
      imaging. Lipolytic digestion and labeling studies suggest monoacylglycerol-3
      phosphate and diacylglycerol (-3-phosphate) structures harboring a single
      fluorescent fatty acyl residue each for lipids 1 and 3 (2), respectively.
      Fluorescent triglycerides are not generated. Assaying acylation with isolated
      microsomes using the purified lipids 1 and 3 indicates that incorporation of one
      fluorescent fatty acyl residue into glycerol(-3-phosphate) interferes with
      subsequent esterification. Pretreatment of the adipocytes with insulin
      significantly stimulates synthesis of lipids 1 and 2, only. The insulin
      concentration-response relationship (EC50 = 0.5 nM) and the maximal insulin
      response for synthesis of lipid 1 (stimulation factor = 14- to 20-fold at low
      glucose and 3- to 7-fold at high glucose) are comparable with those for
      incorporation of [3-3H]glucose into total adipocyte lipids. Thus this
      fluorescence-based assay may be useful for studying insulin action and
      lipogenesis.

PMID- 9233685
TI  - During neuronal and glial cell development diet n-6 to n-3 fatty acid ratio
      alters the fatty acid composition of phosphatidylinositol and phosphatidylserine.
AB  - Brain development was examined in the neonatal rat in response to feeding
      increased levels of 18:3n - 3, 20:4n - 6 or 22:6n - 3 at levels proposed for
      infant formula. Diets varying in n - 6 to n - 3 fatty acid ratio, with or without
      20:4n - 6 and 22:6n - 3 alone or in combination, were fed to nursing dams at
      parturition and subsequently to weaned pups until six weeks of age. Neuronal and
      glial cells were isolated from the frontal, cerebellar and hippocampal brain
      regions of rat pups at birth, one, two, three and six weeks of age. Fatty acid
      analysis of inositol- and serine- phosphoglycerides indicated that small changes
      in dietary n - 6 to n - 3 fatty acid ratio significantly affect neuronal and
      glial cell membrane composition. Fatty acid composition of phosphatidylinositol
      and phosphatidylserine was distinct and exhibited change with age. Individual
      brain regions and cell types varied in amount and rate of 20:4n - 6 and 22:6n - 3
      accretion. Alteration of brain fatty acid composition reflected the fatty acid
      composition of the diet fed. If analogous changes occur during human brain
      development, feeding infants 20:4n - 6 and 22:6n - 3 or a reduced 18:2n - 6 to
      18:3n - 3 ratio may alter fatty acid profiles of brain cells.

PMID- 9233686
TI  - Effects of fatty acids on apolipoprotein B secretion by McArdle RH-7777 rat
      hepatoma cells.
AB  - The effect of oleic acid (OA), stearic acid (SA) and elaidic acid (EA) on
      cellular and secreted apolipoprotein (apo) B was examined in McArdle RH-7777
      (McArdle) hepatoma cells and in primary rat hepatocytes. ApoB secretion by
      McArdle cells was significantly inhibited by 20% in 8 h incubations in medium
      containing EA and SA and by 50% in medium containing OA. In contrast, apo B
      secretion and cellular apo B of primary rat hepatocytes was relatively unaffected
      by incubations in medium containing fatty acids. Both B100 and B48 secretion in
      McArdle wild type and B48 in apo B mRNA editing enzyme catalytic polypeptide
      transfectants expressing B48 were inhibited to a similar extent indicating an
      effect of OA on both apo B species. The effect of OA occurred without changes in
      cellular apo B or in apo B mRNA abundance suggesting a post-transcriptional
      mechanism. Time course studies indicate that the suppressive effect of OA
      requires 4 h of incubation suggesting the depletion of a limiting factor
      important in apoB secretion. By increasing the proportion of palmitic acid to OA
      in the medium, apoB secretion by McArdle cells was progressively restored to
      control levels implicating an unique role for newly synthesized saturated fatty
      acid.

PMID- 9233687
TI  - 2-methylacyl racemase: a coupled assay based on the use of pristanoyl-CoA
      oxidase/peroxidase and reinvestigation of its subcellular distribution in rat and
      human liver.
AB  - Because of the 2S-methyl-stereospecificity of the acyl-CoA oxidases acting on the
      CoA esters of 2-methyl-branched fatty carboxylates such as pristanic acid and the
      side chain of trihydroxycoprostanic acid (Van Veldhoven P.P., Croes K.,
      Asselberghs S., Herdewijn P. and Mannaerts G.P. (1996) FEBS Lett. 388, 80-84),
      naturally occurring 2R-pristanic acid and 25R- (corresponding to 2R in the side
      chain) trihydroxycoprostanic acid, after activation to their CoA-esters, need to
      be racemized to the S-isomers before they can be degraded by peroxisomal beta
      oxidation. A coupled assay to measure 2-methyl-acyl racemases was developed by
      using purified rat pristanoyl-CoA oxidase. Upon incubation of rat and human liver
      homogenates with 2R-methyl-pentadecanoyl-CoA, the formed 2S-methyl isomer was
      desaturated by an excess of added oxidase and the concomitant production of
      hydrogen peroxide was monitored by means of peroxidase in the presence of a
      suitable hydrogen donor. Application of this assay to subcellular fractions of
      rat liver revealed the presence of racemase activity not only in mitochondria, as
      described by Schmitz W., Albers C., Fingerhut R. and Conzelmann E. (Eur. J.
      Biochem. (1995) 231, 815-822), but also in peroxisomes and cytosol. A similar
      distribution was seen in human liver. In rat the highest activities were found in
      liver, followed by Harderian gland, kidney and intestinal mucosa.

PMID- 9233688
TI  - Modification of the N-terminal cysteine of plasma cholesteryl ester transfer
      protein selectively inhibits triglyceride transfer activity.
AB  - An invariant cysteine residue is found at the N-terminus of cholesteryl ester
      transfer protein (CETP) isolated from plasma of humans, rabbits and cynomolgus
      monkeys. We previously reported the expression of recombinant rabbit cholesteryl
      ester transfer protein in yeast (Kotake et al., J. Lipid Res. 1996; 37: 599-605).
      The recombinant CETP secreted into the medium contains an altered N-terminal
      sequence but was fully capable of facilitating both cholesteryl ester (CE) and
      triglyceride (TG) transfer between lipoproteins. We investigated the importance
      of the conserved N-terminal cysteine of plasma CETP in the lipid transfer
      activity by chemical modification of the free sulfhydryl groups of the
      recombinant CETP and CETP from human and rabbit plasma. The unmodified forms of
      these CETPs had similar specific activities of CE and TG transfer. Neither 5,5'
      dithiobis-(2-nitrobenzoate) nor N-ethyl maleimide altered the lipid transfer
      activity. In contrast, p-chloromercuriphenyl sulfonate selectively inhibited the
      TG transfer activity of both human and rabbit plasma CETP. The TG and CE transfer
      activities of the recombinant CETP, which lacks the N-terminal cysteine residue,
      was not affected. These results demonstrate that the N-terminal cysteine residue
      of both human and rabbit plasma CETP is free and is likely to be involved in the
      construction of a critical part of the active site of CETP that can determine the
      selectivity of the lipid molecule for the transfer reaction.

PMID- 9233689
TI  - Oxydation of oleic acid to (E)-10-hydroperoxy-8-octadecenoic and (E)-10-hydroxy-8
      octadecenoic acids by Pseudomonas sp. 42A2.
AB  - Biotransformation of oleic acid with Pseudomonas sp. 42A2 has been found to
      produce(E)-10-hydroxy-8-octadecenoic acid (2a), (E)-10-hydroperoxy-8-octadecenoic
      acid (3a), and (E)-7,10-dihydroxy-8-octadecenoic acid (4a). Structures of the
      metabolites were fully characterized by infrared and 1H and 13C NMR spectra of
      the acids, by fast atom bombardment (FAB) and electron impact (EI) and chemical
      ionization (CI) mass spectrometry of the corresponding methyl esters. This is the
      first time that the two former compounds of trans stereochemistry have been
      described to have originated from a Pseudomonas sp. cell culture. Time course of
      products accumulation showed that biotransformation started with bacterial
      growth, the amount of products 2a (5.58 g/l) and 4a (2.63 g/l) being optimum
      after 24 h of incubation while hydroperoxide 3a (1.15 g/l) reached its maximum
      after 16 h of the biotransformation process. Experiments conducted to ascertain
      whether the conversion enzyme(s) was cell-bound or extracellular, showed that the
      enzyme(s) is cell bound, located in the periplasmic space and has lipoxygenase
      activity.

PMID- 9233690
TI  - Specificity of hydroperoxy fatty acid inhibition of cell growth and the lack of
      effect on tumour necrosis factor-induced cytotoxicity in WEHI clone 13 cells.
AB  - We have examined whether different omega6-hydroperoxy fatty acids affect tumour
      cell growth or modulate TNF-induced toxicity in a fatty acid specific way in WEHI
      clone 13 fibrosarcoma cells. The omega6-hydroperoxides were synthesized from 8
      different n - 6 and n - 3 PUFAs by soybean lipoxygenase. The omega6-hydroperoxy
      fatty acids inhibited cell growth in a concentration-dependent way by a mechanism
      that is related to the hydroperoxy moiety. Intracellular GSH seemed to protect
      since the GSH synthase inhibitor L-buthionine-S,R-sulfoximine (BSO) increased
      cell growth inhibition further. The antioxidants butylated hydroxyanisole (BHA),
      butylated hydroxytoluene and alpha-tocopherol did not affect the toxicity. The
      extent of growth inhibition varied between the hydroperoxides, but the difference
      was relatively small. The most toxic was hydroperoxy-alpha-linolenic acid which
      reduced cell survival by 56% after 44 h incubation at 35 microM, while the least
      toxic, hydroperoxy-gamma-linolenic acid, reduced cell survival by only 10%. The
      data also show that there is no correlation between toxicity and degree of
      unsaturation of the hydroperoxy fatty acids. None of the 8 different hydroperoxy
      fatty acids potentiated TNF-induced toxicity. This, together with the
      differential effects of BHA and BSO on TNF- and hydroperoxy fatty acid toxicity,
      indicate that neither the hydroperoxides nor their metabolites are involved in
      mediating or modulating the TNF-effect.

PMID- 9233691
TI  - Metabolism of dolichol, dolichoic acid and nordolichoic acid in cultured cells.
AB  - The uptake and metabolism of [1-(14)C]-labelled dolichol, dolichoic acid and
      nordolichoic acid were investigated in MDCK and HepG2 cells. Each of the three
      isoprenoids, bound to human serum albumin, was taken up effectively. None of the
      compounds was broken down in HepG2 cells, although these converted dolichol into
      fatty acid esters. In MDCK cells dolichoic acid gave rise to the formation of
      [14C]CO2 and radiolabelled formic acid, indicating that dolichoic acid can be
      broken down by alpha-oxidation. Dolichoic acid was also converted to a mixture of
      polar compounds, possibly polyols. MDCK cells generated radiolabelled CO2 from
      nordolichoic acid, presumably through beta-oxidation, although we could not find
      any labelled propionic acid. No oxidative breakdown of dolichol was found,
      apparently due to the lack of or very low conversion to dolichoic acid.

PMID- 9233692
TI  - Balancing the immune system for tolerance: a case for regulatory CD4 cells.
AB  - In the past, tolerance mechanisms have focused on processes that involve
      elimination (deletion) or paralysis (anergy) of immune responses. It is now
      becoming clearer that peripheral tolerance to antigen depends on the generation
      of regulatory cells that function to maintain the tolerant state. The development
      of peripheral tolerance may require that the immune system utilize several
      strategies, including deletion, anergy, and immunoregulatory pathways, and these
      strategies may overlap. Recent investigations using animal models of
      transplantation tolerance have demonstrated that immunoregulatory CD4 mechanisms
      may play a central role in limiting organ-destructive immune responses. In this
      Overview, we discuss the rationale behind the need for invoking active regulatory
      mechanisms in peripheral immunologic tolerance and summarize the data that
      support or refute a CD4 regulatory mechanism.

PMID- 9233693
TI  - Massive repopulation of rat liver by transplantation of hepatocytes into specific
      lobes of the liver and ligation of portal vein branches to other lobes.
AB  - An important consideration in application of hepatocyte transplantation is
      whether the number of engrafted hepatocytes is sufficient to achieve the desired
      effect. Here we have evaluated the proliferative potential of transplanted
      primary hepatocytes during regeneration of hepatic lobes. Two million hepatocytes
      isolated from congeneic normal Wistar-RHA rats were injected into the main portal
      vein of deficient, jaundiced Gunn rats. The right branch of the portal vein was
      ligated 24 hr before hepatocyte transplantation (group A) or transiently clamped
      during hepatocyte injection (group B) or 24 hr after hepatocyte injection (group
      C). In these groups, the three lobes supplied by the right branch of the portal
      vein rapidly atrophied and disappeared in 4 days, whereas the remaining lobes
      proliferated, as shown by size increase and 5-bromo-2-deoxy-uridine uptake. Two
      control groups received 2 million (group D) or 20 million hepatocytes (group E)
      without ligation. Hepatocyte engraftment occurred in all groups. The greatest
      hypobilirubinemic effect was observed in group A, in which serum bilirubin
      concentrations were reduced to 1.7+/-0.45 mg/dl from pretransplantation levels of
      6.9+/-1.2 mg/dl. This effect was even greater than that observed after
      transplantation of 20 times more hepatocytes without ligation (group E). Specific
      endonuclease digestion of a polymerase chain reaction-amplified segment of the
      ugt1 gene from hepatic DNA showed that up to 25% of the DNA was of donor origin.
      This paralleled the hepatic bilirubin-UDP-glucuronosyltransferase activity, which
      was above 50% of normal. The results indicate that the transplanted hepatocytes
      proliferate preferentially within the regenerating lobes, replacing more than 20%
      of the liver mass with the progeny of the transplanted phenotypically normal
      hepatocytes.

PMID- 9233694
TI  - Synthetic MHC class I peptide prolongs cardiac survival and attenuates transplant
      arteriosclerosis in the Lewis-->Fischer 344 model of chronic allograft rejection.
AB  - BACKGROUND: A synthetic peptide corresponding to residues 75-84 of the alpha1
      domain of HLA-B7 molecule (HLA-B7.75-84 [Allotrap]) inhibits cytotoxic T cell
      function in vitro and, when combined with subtherapeutic doses of cyclosporine
      (CsA), prolongs allogeneic cardiac survival. We now report the effects of HLA
      B7.75-84 in the Lewis --> Fischer 344 rat model of chronic cardiac allograft
      rejection. METHODS: Animals were treated with CsA (5 mg/kg/day s.c.) alone or
      with CsA plus alternate-day HLA-B7.75-84 (20 mg/kg/day i.p.) for 30 days.
      Allografts harvested at day 100 were evaluated by histology and immunohistology.
      RESULTS: HLA-B7.75-84 plus CsA prolonged allograft survival (75% of allografts
      survived >90 days) compared with CsA alone (27% of allografts survived >90 days)
      (P<0.05). Histologic examination of control allografts showed dense cellular
      infiltrates and moderate transplant arteriosclerosis (>75% of arteries showed 10
      20% occlusion). Infiltrating leukocytes consisted of macrophages (>75% cells), T
      cells (10-20%), and rare natural killer cells (<5%). Cell activation was shown by
      expression of major histocompatibility complex class II antigens (>75%),
      interleukin (IL) 2 receptor (5-10%), and staining for IL-2 (approximately 5% of
      intragraft mononuclear cells), interferon-gamma (5-10%) and tumor necrosis factor
      alpha (approximately 20%). Leukocytes and vessels also showed labeling for the
      fibrogenic cytokine, transforming growth factor-beta, and all vessels showed
      dense deposition of IgG (IgG2a, IgG2b) and C3. The addition of HLA-B7.75-84
      decreased overall cellularity (P<0.01) without affecting the composition of the
      infiltrate, but completely prevented transplant arteriosclerosis, diminished
      myocardial injury, and abrogated expression of IL-2R, IL-2, interferon-gamma,
      tumor necrosis factor-alpha, and transforming growth factor-beta. HLA-B7.75-84
      also blunted the humoral response, which resulted in a predominance of vascular
      deposition of the non-complement-fixing IgG2c isotype and a concomitant decrease
      in C3. CONCLUSIONS: Therapy with synthetic class I major histocompatibility
      complex peptide (HLA-B7.75-84) attenuates key histologic features of graft
      arteriosclerosis, in association with inhibition of multiple cytokines and growth
      factors and modulation of host alloantibody responses in vivo, which is of
      interest since Allotrap is currently undergoing clinical trials.

PMID- 9233695
TI  - Allo- and autotransplantation of carotid artery--a new model of chronic graft
      vessel disease: evaluation by magnetic resonance imaging and histology.
AB  - BACKGROUND: Graft vessel disease is a special form of accelerated
      arteriosclerosis. Because immunological and nonimmunological factors can
      contribute to graft vessel disease, we developed a model that enables the study
      of both factors simultaneously. METHODS: A carotid artery was allografted from DA
      to Lewis rats, with the excised native artery autografted on the contralateral
      side. Five groups of six to seven rats were treated for 8 weeks with vehicle
      (placebo) or cyclosporine (CsA) (0.3, 1, 3, and 10 mg x kg(-1) x day(-1)), which
      was administered using subcutaneous osmotic minipumps. The carotid lumen area was
      estimated in vivo at 2, 4, and 8 weeks by magnetic resonance imaging (MRI); CsA
      blood levels were determined twice. Carotid neointimal thickening and medial and
      luminal area were measured with histological techniques. RESULTS: MRI showed
      bulging of the allografts but not autografts. Bulging disappeared over time with
      narrowing of the allograft lumina estimated by both MRI and histology.
      Histologically, vehicle-treated animals developed a massive neointima, which was
      inhibited in a dose-dependent manner by CsA. Autografts remained normal except
      for minimal subintimal thickening of two of four arteries in the group given the
      highest dose of CsA. Cellular rejection was detected in the allografts of all but
      the highest-dose group. The CsA blood levels were similar to those used in man at
      the two lower doses and about 10-fold higher at the highest dose. CONCLUSIONS:
      Subintimal thickening did not correlate with in vivo lumen size, a phenomenon
      that we have previously described for balloon catheter-induced lesions. CsA blood
      concentrations similar to those used in patients suppressed neointima formation
      in part, and 10-fold higher concentrations almost completely suppressed neointima
      formation.

PMID- 9233696
TI  - Long-term function of fish islet xenografts in mice by alginate encapsulation.
AB  - BACKGROUND: Large, anatomically discrete pancreatic islets, Brockmann bodies
      (BBs), exist in certain teleost fish. When transplanted under the renal capsules
      of streptozotocin-diabetic athymic nude mice, BB grafts produce uniform
      normoglycemia for 50 days and mammalian-like glucose tolerance profiles; however,
      these very discordant islets reject in 7-8 days when transplanted into euthymic
      BALB/c mice. METHODS: In the present study, BBs were mass harvested, minced into
      <1-mm tissue fragments, and encapsulated in alginate-based macrospheres (5 mm
      diameter) or noodles (0.5x3 cm). Nonencapsulated and encapsulated BB fragments
      were transplanted intraperitoneally into streptozotocin-diabetic (nonfasting
      blood glucose >400 mg/dl) nu/nu and BALB/c mice. Glucose levels were monitored at
      least 3 times a week. RESULTS: Encapsulated BB grafts uniformly survived >50 days
      (10/10) or >100 days (3/3) in nu/nu recipients. The mean graft survival time was
      27+/-13 days in BALB/c recipients (n=7). Daily intraperitoneal administration of
      2.5 mg/kg 15-deoxyspergualin, in combination with encapsulation, resulted in
      uniform long-term BB graft function in BALB/c recipients (n=5). Similarly, long
      term function was achieved in four of six BALB/c recipients with daily
      intraperitoneal administration of 10 mg/kg cyclosporine (two grafts failed after
      39 and 45 days). Nonencapsulated BB grafts transplanted intraperitoneally into
      BALB/c or nu/nu recipients functioned for <7 days; immunosuppression alone did
      not permit graft survival in BALB/c recipients. In all cases of graft survival of
      >50 days, grafts were surgically removed from the peritoneal cavity, and blood
      sugar levels returned to a diabetic state within a few days. Historical sections
      of grafts, stained with hematoxylin and eosin and immunoperoxidase for insulin,
      showed viable, well-granulated BB tissue. CONCLUSIONS: This study demonstrates
      that tilapia BBs are suitable for encapsulation and that encapsulated BBs can be
      made to function long term in diabetic mice.

PMID- 9233697
TI  - SDZ RAD, a new rapamycin derivative: synergism with cyclosporine.
AB  - BACKGROUND: SDZ RAD is a new rapamycin analog with potent immunosuppressive
      activity. Compounds of the rapamycin class differ in their mode of action from
      cyclosporine, thus providing a rationale for potential synergism of these two
      potent immunosuppressants. METHODS: The two-way mouse mixed lymphocyte reaction
      (BALB/c-CBA strain combination) was applied. Orthotopic kidney and heterotopic
      heart allografting was performed in the stringent DA-to-Lewis rat strain
      combination, with administration of compounds orally as microemulsion
      preconcentrate (i.e., Neoral in the case of cyclosporine). RESULTS: Isobologram
      analysis of checkerboard titrations of SDZ RAD and cyclosporine in two-way mouse
      mixed lymphocyte reactions indicates a synergistic interaction in vitro. In vivo,
      the minimal effective dose of microemulsion cyclosporine giving long-term graft
      survival was 5.0 mg/kg/day; for SDZ RAD, the minimal effective dose was 5.0
      mg/kg/day in kidney transplantation and >5.0 mg/kg/day in heart transplantation.
      Long-term allograft survival was noted for combinations of microemulsion
      cyclosporine administered at 1.0 or 2.0 mg/kg/day and SDZ RAD given at between
      0.5 and 2.0 mg/kg/day. The index of synergy in different combinations ranged
      between 0.3 and 0.7. CONCLUSIONS: SDZ RAD and cyclosporine show synergism in
      immunosuppression, both in vitro and in vitro. They form a promising synergistic
      drug combination in allotransplantation.

PMID- 9233698
TI  - SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in
      vivo.
AB  - BACKGROUND: This report describes the preclinical pharmacological profile of the
      new rapamycin analog, SDZ RAD, i.e., 40-O-(2-hydroxyethyl)-rapamycin. METHODS:
      The pharmacological effects of SDZ RAD were assessed in a variety of in vitro and
      in vivo models, which included an autoimmune disease model as well as kidney and
      heart allotransplantation models using different rat strain combinations.
      RESULTS: SDZ RAD has a mode of action that is different from that of cyclosporine
      or FK506. In contrast to the latter, SDZ RAD inhibits growth factor-driven cell
      proliferation in general, as demonstrated for the in vitro cell proliferation of
      a lymphoid cell line and of vascular smooth muscle cells. SDZ RAD is
      immunosuppressive in vitro as demonstrated by the inhibition of mouse and human
      mixed lymphocyte reactions and the inhibition of antigen-driven proliferation of
      human T-cell clones. The concentrations needed to achieve 50% inhibition in all
      of these assays fall into the subnanomolar range. SDZ RAD is effective in the in
      vivo models when given by the oral route in doses ranging between 1 mg/kg/day and
      5 mg/kg/day. When compared with rapamycin, the in vitro activity of SDZ RAD is
      generally about two to three times lower; however, when administered orally, SDZ
      RAD is at least as active in vivo as rapamycin. CONCLUSIONS: In conclusion, SDZ
      RAD is a new, orally active rapamycin-derivative that is immunosuppressive and
      that efficiently prevents graft rejection in rat models of allotransplantation.
      SDZ RAD has therefore been selected for development for use in combination with
      cyclosporine A to prevent acute and chronic rejection after solid organ
      allotransplantation.

PMID- 9233699
TI  - Mechanism of concordant corneal xenograft rejection in mice: synergistic effects
      of anti-leukocyte function-associated antigen-1 monoclonal antibody and FK506.
AB  - BACKGROUND: The mechanisms of corneal xenogeneic immunoreaction, as well as the
      potential role of immunosuppressive therapy in the suppression of corneal
      xenograft rejection, have not been thoroughly explored. METHODS: BALB/c mice who
      received orthotopic corneal transplants (Lewis rats donors) were administered
      intraperitoneally anti-leukocyte function associated antigen-1 (LFA-1) monoclonal
      antibody (mAb) or FK506 (3 mg/kg/day) or both of these immunosuppressants during
      a 12-day postoperative period. Histological (hematoxylin-eosin stain) and
      immunohistochemical evaluations of enucleated eyes were performed. Humoral immune
      response and delayed-type hypersensitivity (ear-swelling assay) were evaluated.
      RESULTS: The mean (+/-SD) graft survival time in the untreated control, FK506
      treated, anti-LFA-1 mAb-treated, and combined-treatment groups was 5.8+/-0.8,
      9.4+/-4.0, 8.7+/-5.0, and 67.7+/-16.4 days, respectively. In the untreated
      control group, mouse IgG, IgM, and C3 were expressed on the rat corneal grafts
      during the early postoperative phase. Flow cytometry studies revealed high titers
      of xenoreactive IgG and IgM antibodies. T helper 1 cytokines were expressed on
      xenografted corneal beds, and delayed-type hypersensitivity was induced. However,
      local expression of IgM, C3 and T helper 1 cytokines, serum antibodies of IgG and
      IgM, and delayed-type hypersensitivity were suppressed in the anti-LFA-1 mAb-
      plus FK506-treated group. CONCLUSIONS: Both humoral and cell-mediated immune
      reaction play an important role in the initial rejection in rat-to-mouse corneal
      xenotransplantation. The treatment with anti-LFA-1 mAb in combination with FK506
      synergistically suppresses concordant corneal xenogeneic reaction.

PMID- 9233700
TI  - Treatment of graft-versus-host disease by extracorporeal photochemotherapy: a
      pilot study.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after bone
      marrow transplantation, which may be refractory to immunosuppressive drugs. As
      preliminary case reports suggested that extracorporeal photochemotherapy (ECP)
      using a Therakos device might be beneficial, we conducted a pilot study to assess
      the efficacy and safety of a new ECP method that does not require administration
      of 8-methoxypsoralen (8-MOP) to the patient. METHODS: ECP was performed three
      times a week for 3 weeks and then tapered according to the patient's course.
      Soluble 8-MOP was added ex vivo to an enriched mononuclear cell suspension
      obtained by a cell separator. This cellular suspension was then ultraviolet A
      irradiated and reinfused into the patient. Evaluation was performed using
      specific objective tests depending on clinical conditions. RESULTS: The two
      patients in the study with acute GVHD and severe liver dysfunction resistant to
      steroid pulse showed no improvement with ECP treatment. The five patients with
      chronic GVHD (c-GVHD) had the following clinical features: three patients had
      myositis and two patients had severe cutaneous c-GVHD, including one patient with
      sclerodermoid lesions, one with bronchiolitis obliterans, one with bronchitis,
      and one with liver involvement. Immunosuppressive drugs were either prohibited or
      ineffective. The number of procedures for each patient ranged from 13 to 30.
      Cytapheresis required the use of a double-lumen catheter (4/5) or an
      arteriovenous fistula (1/5). No side effects were related to 8-MOP or ultraviolet
      A irradiation. Four of five patients improved after ECP; one patient with
      bronchiolitis obliterans, a fibrotic condition, remained stable. CONCLUSIONS: ECP
      treatment may be helpful for the treatment of severe c-GVHD and the avoidance of
      increased immunosuppression.

PMID- 9233701
TI  - A positive crossmatch in liver transplantation--no effect or inappropriate
      analysis? A prospective study.
AB  - BACKGROUND: Controversy over the relationship of preformed lymphocytotoxic
      antibodies and liver graft outcome remains. Because graft loss associated with
      preformed lymphocytotoxic antibodies probably occurs early after transplant,
      analysis of long-term survival is of questionable value. We therefore
      prospectively analyzed the effect on short- and long-term graft survival of the
      presence of lymphocytotoxic alloantibody in 207 primary adult liver allograft
      recipients. METHODS: Pretransplant serum was tested for donor-specific
      lymphocytotoxic antibodies and panel-reactive antibodies (PRA) using donor
      splenic lymphocytes and lymphocytes obtained for routine tissue typing. RESULTS:
      A positive crossmatch was detected in 24 recipients (11.5%): T-cell positive in
      11 recipients and B-cell positive in 13 recipients. PRA were detected in 68 of
      179 recipients tested (37.4%). High T-cell PRA (>55%) was detected in 17
      recipients, and high B-cell PRA was detected in 20 recipients. Low PRA (<15%)
      against T cells was detected in 19 recipients and against B cells in 24
      recipients. Graft failures occurred in 5 of 24 (21%) crossmatch-positive
      recipients and in 7 of 172 (4%) crossmatch-negative recipients. Graft survival
      was significantly lower in crossmatch-positive recipients at 1 month after
      transplant (chi-square=10.3, P=0.00133) but not at 3 months or 1 year. Causes of
      early graft loss were associated with immunological mechanisms, whereas later
      losses were due to nonimmunological mechanisms. CONCLUSIONS: Early graft loss may
      be increased in those recipients who are crossmatch positive. However, the
      logistical problems and consequences associated with allocation probably outweigh
      the benefits of prospective crossmatching.

PMID- 9233702
TI  - Value of the in vitro or in vivo monoethylglycinexylidide test for predicting
      liver graft function.
AB  - BACKGROUND: An adequate function test for donor livers is still lacking. The
      monoethylglycinexylidide (MEGX) test, performed in vivo in the donor to measure
      the metabolic rate of lidocaine conversion to MEGX, has been proposed as a
      function test for donor livers to predict postoperative organ function. METHODS:
      In the present study, we investigated whether the MEGX formation rate measured in
      needle biopsy specimens in vitro correlates with the rate of MEGX formation in
      vivo. The in vivo MEGX test was performed in the donors and in the recipients on
      days 1 and 2. The in vivo and in vitro MEGX tests were compared with
      posttransplant liver function in the recipients in order to investigate their
      possible relevance as predictors of graft function. RESULTS: The MEGX formation
      rate in needle biopsy specimens in vitro showed a significant correlation with
      the MEGX serum concentration found in the donor. A low rate of MEGX formation in
      the biopsy specimens tended to predict initial poor function of the grafts. In
      the donor, the MEGX test did not correlate with general liver function after
      transplantation. Only the MEGX serum concentration in the recipients on day 2
      gave an indication of graft function. CONCLUSIONS: MEGX formation in liver biopsy
      specimens in vitro properly reflects metabolic function of the particular liver.
      Therefore, liver biopsies may be a valuable tool to help predict liver function
      in vivo. However, the MEGX test alone is not sufficient to provide the gold
      standard to determine liver function in donor and transplantation livers.

PMID- 9233703
TI  - Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized
      trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK
      Liver Transplantation Database.
AB  - BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV)
      infection and disease in orthotopic liver-transplant patients remains to be
      established. We tested whether a combination of intravenous ganciclovir (GCV)
      followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher
      degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty
      seven liver-transplant recipients were randomized to receive 120 days of
      antiviral treatment starting at the time of transplantation consisting of either
      ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously
      every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective
      laboratory and clinical surveillance was performed to determine primary endpoints
      (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal
      and bacterial infection, allograft rejection, and survival after
      transplantation). One-year event rates are presented as cumulative percentages.
      RESULTS: During the first year after transplantation, CMV infection developed in
      57% of patients treated with ACV and in 37% of patients treated with GCV + ACV
      (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11%
      of patients treated with GCV + ACV (P=0.03). In seronegative recipients of
      allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of
      patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04).
      In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated
      with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS:
      Prophylaxis of CMV infection in liver-transplant patients with 14 days of
      intravenous GCV followed by high-dosage oral ACV is more effective than high
      dosage oral ACV alone at reducing CMV infection and disease, even for patients in
      the D+/R- CMV serological group.

PMID- 9233704
TI  - Progression of ventricular wall thickening after liver transplantation for
      familial amyloidosis.
AB  - BACKGROUND: Familial amyloidosis (FAP) is characterized by the progression of
      neurologic and cardiac impairment ultimately leading to death within 7 to 15
      years after the onset of the disease. Liver transplantation represents the only
      definitive therapy for this disease and has been performed since 1990. METHODS:
      To determine the effect of liver transplantation on disease progression,
      electrocardiography and Doppler echocardiography were performed and blindly
      analyzed on 11 patients with FAP who were followed 0.8 to 8.6 years before liver
      transplantation and 0.8 to 4.1 years after liver transplantation. RESULTS; After
      liver transplantation, five patients showed progression of left ventricular wall
      thickening with increased left ventricular mass, and three of these five showed a
      reduction in electrocardiographic voltage despite abolition of the mutant protein
      from the serum. Of the five patients showing progressive wall thickening, four
      had the transthyretin variant Glu 42 Gly and one patient had the Ala 36 Pro
      variant; none of the remaining six patients, all of whom possessed the Val 30 Met
      variant, showed echocardiographic changes. Although 9 of the 11 patients have
      shown symptomatic improvement in neurologic symptoms, 1 patient has developed
      heart failure and a second patient has suffered a sudden cardiac death.
      CONCLUSIONS: After liver transplantation, patients with FAP should have regular
      clinical evaluations including electrocardiographic and echocardiographic
      examinations to look for continued deterioration in heart structure or function.

PMID- 9233705
TI  - National kidney allograft sharing: a decision analysis.
AB  - BACKGROUND: Expansion of the current program of national sharing of cadaveric
      kidney allografts is of uncertain benefit, and the logistical barriers to
      expanding organ sharing are large. This study estimated the improvement in
      allograft survival from expanding organ sharing in the United States. METHODS: A
      decision analysis based on allograft survival data from cadaveric allograft
      recipients throughout the United States compared the mean allograft survival
      resulting from four allograft-sharing strategies: no national sharing, national
      sharing of allografts matched at 6 histocompatibility alleles, national sharing
      of allografts matched at 4 or more alleles, and national sharing of allografts
      matched at 2 or more alleles. RESULTS: Sharing allografts matched at 4 or more
      alleles was optimal (mean allograft survival=6.35 years). This survival was
      little better than the mean survival of the other three strategies (no national
      sharing, 6.21 years; national sharing of allografts matched at 6 alleles, 6.31
      years; and sharing of allografts matched at 2 or more alleles, 6.33 years). The
      increment in the proportion of allografts surviving 4 years or more under the
      optimal strategy compared with no national sharing was <2%. A similar decision
      model comparing kidney transplant outcomes before and after the introduction of
      cyclosporine showed that this drug has had a much greater impact on mean
      allograft survival than would be expected to occur with national allograft
      sharing: 6.07 years with cyclosporine versus 3.79 years without cyclosporine.
      CONCLUSIONS: Expanding national allograft sharing would achieve little
      improvement in mean allograft survival. The limited benefit and logistical
      barriers to expansion of allograft sharing should be considered before following
      recommendations to expand the current U.S. allograft-sharing program.

PMID- 9233706
TI  - Retroperitoneal laparoscopic nephrectomy of native kidneys in renal transplant
      recipients.
AB  - BACKGROUND: The purpose of this study was to compare retroperitoneal laparoscopic
      nephrectomy in transplant recipients and in other patients scheduled for
      nephrectomy. METHODS: From February 1994 to July 1996, 15 transplant recipients
      and 17 other patients underwent a total of 36 retroperitoneal laparoscopic
      nephrectomies for various indications. Operative time, morbidity, and hospital
      stay were compared between the two groups. RESULTS: The average operating time
      for the 36 procedures was 95+/-38 min (range, 35-180 min). It was shorter in
      transplant recipients (81+/-32 min) than in other patients (100+/-39 min,
      P<0.05). There was one postoperative complication in the transplant recipient
      group. The average length of the postoperative hospitalization was 3.7+/-1.4 days
      (range, 2-8 days). CONCLUSIONS: The retroperitoneal laparoscopic approach for
      nephrectomy is as safe and effective in renal transplant recipients as in other
      patients. Postoperative stay and delay to resumption of oral immunotherapy are
      short. This approach has become our first-line approach for native nephrectomy in
      transplant recipients.

PMID- 9233707
TI  - Renal function in cyclosporine-treated pediatric renal transplant recipients in
      relation to gingival overgrowth.
AB  - BACKGROUND: Transplant immunosuppression using cyclosporine (CsA) leads to renal
      dysfunction as well as gingival overgrowth. The underlying alteration in both
      these lesions is characterized by an excessive accumulation of extracellular
      matrix components (fibrosis). To investigate the relationship between CsA-induced
      nephrotoxicity and gingival overgrowth, the renal function as well as the
      occurrence of gingival overgrowth was evaluated in pediatric renal transplant
      recipients: 38 boys and 30 girls, ranging in age from 2 to 20 years, who had been
      on a CsA-based immunosuppressive regimen for at least 12 months. METHODS:
      Gingival overgrowth was determined on the basis of measurements of sulcus depth
      and was diagnosed as positive when the probing depth was > or = 4 mm without
      exhibiting a loss of periodontal attachment. Renal function tests were performed
      using inulin and para-aminohippuric acid clearances for evaluating glomerular
      filtration rate, effective renal plasma flow (ERPF), and filtration fraction
      (FF). RESULTS: Nineteen percent of the children exhibited gingival overgrowth.
      The occurrence of gingival overgrowth was positively related (P<0.05) to the mean
      oral daily dose of CsA, the mean CsA trough blood level, and concomitant
      administration of nifedipine. The children who were on antihypertensive treatment
      exhibited lower ERPF and significantly higher FF than the normotensive children.
      The mean FF value was significantly higher (P<0.05) in the children with gingival
      overgrowth than in those without gingival overgrowth, whereas glomerular
      filtration rate and ERPF did not differ between the two groups. CONCLUSIONS: The
      study suggests that there is a positive correlation between the degree of
      gingival enlargement and changes in renal function expressed as filtration
      fraction.

PMID- 9233708
TI  - Analysis of fine-needle aspiration biopsies by flow cytometry in kidney
      transplant patients.
AB  - BACKGROUND: Peripheral blood lymphocyte (PBL) analysis by flow cytometry has been
      inconsistently reported as an adjunctive method for diagnosing acute kidney
      transplant rejection. However, there is good evidence that lymphocytes
      infiltrating renal grafts differ from those found at the peripheral level. We
      hypothesized that the study of aspiration biopsy samples in conjunction with PBL
      by flow cytometry would enable us to diagnose acute rejection crisis reliably.
      METHODS: Lymphocytes from PBL and aspiration biopsies of kidney transplant
      patients were analyzed. Fifty-one stable patients, rejection-free for the first 6
      months, were studied on day 7 and day 30 after transplantation and were compared
      with 32 patients with 40 acute rejection episodes. RESULTS: Significant
      differences were observed for several lymphocyte subpopulations on aspiration
      biopsy samples comparing stable patients with rejection patients. In contrast,
      PBL analysis was not helpful in differentiating the two groups of patients. By
      combining the expression of several activation markers inside the graft with
      CD3DR and CD3CD25 aspiration biopsy to peripheral blood ratios, we obtained very
      good values for sensitivity and specificity-83.9% and 90.5%, respectively. The
      positive predictive value for rejection among dysfunctional grafts reached 85.8%.
      CONCLUSIONS: Flow cytometry study of aspiration biopsy samples of kidney
      transplant patients is a reliable and powerful method to diagnose acute rejection
      episodes, although it is needed to consider several lymphocyte phenotypes;
      cytofluorometric analysis of PBL is important because it provides graft
      infiltrating cell to peripheral blood lymphocyte ratios. This safe and rapid test
      may significantly improve the management of kidney transplant patients.

PMID- 9233709
TI  - Long-term graft outcome is not necessarily affected by delayed onset of graft
      function and early acute rejection.
AB  - BACKGROUND: Both acute rejection episodes and delayed graft function (DGF) have
      been shown to be associated with decreased 1-year renal allograft survival. In
      our center, the incidence and the intensity of acute rejection episodes have been
      reduced by cyclosporine-based triple-drug therapy. We have also shown that DGF
      alone is not a risk factor for long-term graft survival. METHODS: We have now
      investigated whether an acute rejection episode together with DGF significantly
      effects long-term graft outcome. This study involved 862 first cadaveric renal
      allografts and 182 regrafts. RESULTS: The incidence of DGF was 33% after first
      transplants and 44% after retransplants. The overall incidence of acute rejection
      episodes was 23% in first grafts and 28% in regrafts. After first grafts, there
      were no statistically significant differences in graft survival rates and half
      lives between the early graft function (EGF) and DGF groups with or without acute
      rejection. In regrafts, graft survival was significantly higher in the EGF group
      without acute rejection than in the DGF group with acute rejection. However, if
      all other causes except chronic rejection were censored, the half-life in the EGF
      group without acute rejection was 17.3 years in first grafts, and in the DGF
      group with acute rejection, that number was 11.5 years in first grafts; for
      regrafts, the half-life was 12.3 years and 6.1 years, respectively. CONCLUSIONS:
      Acute rejection together with DGF could contribute to initial damage to the
      graft, and this might lead to later chronic allograft failure. In our study, this
      effect was evident only in the case of retransplants.

PMID- 9233710
TI  - Plasma polymerase chain reaction for cytomegalovirus DNA after allogeneic marrow
      transplantation: comparison with polymerase chain reaction using peripheral blood
      leukocytes, pp65 antigenemia, and viral culture.
AB  - In a prospective longitudinal study, detection of cytomegalovirus (CMV) DNA in
      plasma (plasma polymerase chain reaction [PCR]) was compared with PCR of CMV DNA
      in peripheral blood leukocytes (PBL PCR), the CMV pp65 antigenemia assay, and
      viral cultures from blood, urine, and throat of 29 patients, 14 of whom received
      pp65 antigenemia-guided early ganciclovir treatment and 15 of whom received
      ganciclovir at engraftment. Among 328 blood samples tested by all methods, PBL
      PCR was the most sensitive test, followed by the pp65 antigenemia assay, plasma
      PCR, and viremia. In the 14 patients who received pp65 antigenemia-guided early
      treatment, the incidence of PBL PCR, pp65 antigenemia, plasma PCR, and viremia
      before day 100 was 79%, 79%, 71%, and 27%, respectively, with a median day of
      onset of day 32, 42, 45, and 51, respectively. Nine patients (64%) became
      positive by PBL PCR, pp65 antigenemia, and plasma PCR. Of 15 patients who were
      treated with ganciclovir at engraftment, 12 (80%) became positive by PBL PCR,
      plasma PCR, and/or pp65 antigenemia while receiving ganciclovir; 3 (20%) had
      breakthrough infection with all three methods, including 2 with high-grade
      antigenemia (more than three positive cells in duplicate staining); none of these
      patients subsequently developed positive CMV cultures or disease. In 49
      specimens, PBL PCR and/or pp65 antigenemia assay could not be performed because
      of insufficient neutrophil counts. In conclusion, the sensitivity of plasma PCR
      is significantly lower than that of PBL PCR but similar to that of the pp65
      antigenemia assay. Plasma PCR may be particularly useful in clinical situations
      in which a less sensitive and possibly more specific assay is warranted or in
      which leukocyte counts are inadequate to perform cell-based assays.

PMID- 9233711
TI  - Bone marrow and splenocyte coculture-generated cells enhance allograft survival.
AB  - BACKGROUND: Protocols that incorporate donor-specific cell infusions using bone
      marrow, spleen, or blood transfusion continue to enhance allograft survival and
      often lead to tolerance in experimental models. Clinical benefits from these
      modalities have not been as striking, leading to ongoing study in this field. We
      have explored culture techniques for the in vitro selection and development of
      cellular effectors capable of enhancing allograft survival. METHODS: Rat bone
      marrow or spleen cells cultured under a variety of conditions were screened for
      suppressor function. Bone marrow cells, nonadherent to plastic, cultured for 7
      days with granulocyte-macrophage colony-stimulating factor, lipopolysaccharide,
      and with or without splenocytes were found to contain predominantly myeloid
      lineage cells and had the ability to suppress phytohemagglutinin or mixed
      lymphocyte reaction-induced splenocyte proliferation. Standard donor-specific
      peripheral blood transfusion was compared with cultured donor-specific bone
      marrow cells, splenocytes, or marrow cells cultured with splenocytes (cocultured)
      administered intravenously at 1 x 10(7) cells/kg the day before an ACI to Lewis
      heterotopic heart transplant. Cyclosporine was administered at 10 mg/kg on day -1
      and 2.5 mg/kg on days 0-6 relative to transplantation. RESULTS: Mean allograft
      survival in cyclosporine-treated animals was 8.5 days without and 16.6 days with
      a donor-specific blood transfusion. Cocultured cells extended allograft survival
      (39.5 days), whereas bone marrow or splenocytes cultured alone did not. With
      Percoll gradient separation, two predominant culture subfractions, one with
      potent suppressor function and another with stimulator function, were identified.
      Flow cytometric analysis showed mixed populations enriched for macrophages but
      also including dendritic cells in both subfractions. The suppressive fraction
      extended allograft survival to 20.8 days and the stimulatory fraction was less
      effective, yet remixing of both fractions regained the full allograft survival
      advantage. CONCLUSIONS: In this model, the coculture of bone marrow cells and
      splenocytes with granulocyte-macrophage colony-stimulating factor and
      lipopolysaccharide produced functionally divergent subpopulations that
      synergistically enhanced allograft survival. The development of cellular
      effectors with enhanced ability to prolong allograft survival using in vitro
      culture techniques is possible, and provides a new therapeutic option in the use
      of cell infusion-based therapies.

PMID- 9233712
TI  - Preclinical studies of allograft tolerance in rhesus monkeys: a novel anti-CD3
      immunotoxin given peritransplant with donor bone marrow induces operational
      tolerance to kidney allografts.
AB  - A major challenge in clinical transplantation today is to design a practical and
      effective protocol for tolerance induction compatible with cadaver organ
      transplantation. A preclinical rhesus monkey kidney allograft model using
      immediate peritransplant anti-CD3 immunotoxin (anti-CD3-IT) and donor bone marrow
      (DBM) is shown here to induce operational tolerance with prolonged graft survival
      in the absence of chronic immunosuppressive drugs. Bone marrow harvested from the
      kidney donor was depleted of mature alloantigen-presenting cells and T cells by
      removing DR(bright) cells and CD3(bright) cells, respectively. In outbred, major
      histocompatibility complex-incompatible donor-recipient pairs with high
      pretransplant mixed lymphocyte response and cytotoxic T lymphocyte precursor
      activity, four of six allografts survived for periods of 120 days to >1.5 years.
      Graft acceptance after peritransplant treatment followed robust elimination of
      both peripheral blood T cells and lymph node T cells. In most recipients given
      anti-CD3-IT and DBM infusion, anti-donor immunoglobulin G responses were
      completely inhibited. Microchimerism was observed in all recipients studied,
      including those not given DBM, but levels of microchimerism did not correlate
      with graft survival. Anti-CD3-IT induction in combination with modified DBM
      protocols such as the depletion of mature T cells and DR(bright) antigen
      presenting cells may offer new opportunities to improve clinical tolerance
      protocols beyond those attempted in the clinic to date. Overall, these results
      with anti-CD3-IT show promise for development of cadaver transplant tolerance
      induction.

PMID- 9233713
TI  - Portal venous transfusion up-regulates Kupffer cell cyclooxygenase activity: a
      mechanism of immunosuppression in organ transplantation.
AB  - Portal venous transfusions (PVTs) of blood have been shown to induce significant
      immunosuppression in animal models of organ transplantation. A proposed mechanism
      of PVT-induced immunosuppression is via alteration of Kupffer cell arachidonic
      acid metabolism with increased secretion of the suppressive metabolite
      prostaglandin E2 (PGE2). This study assessed the hypothesis that PVT increases
      Kupffer cell PGE2 production via up-regulation of Kupffer cell phospholipase A2
      (PLA2) as well as constitutive (COX1) and inducible (COX2) cyclooxygenase.
      Kupffer cells from Lewis rats were harvested 1 hr after PVT with either 1 ml of
      Wistar-Furth blood, systemic transfusion (SVT), or saline via portal vein
      (PVSal). After lipopolysaccharide stimulation, 24-hr Kupffer cell supernatant
      fractions were assayed for PGE2. PGE2 was increased after SVT (1465+/-234 pg/ml)
      compared with PVSal (597+/-99; P<0.01). PVT increased Kupffer cell PGE2 (5370+/
      533; P<0.001 vs. SVT and vs. PVSal) even more substantially. Kupffer cells from
      PVT-treated rats were then cultured in the presence of inhibitors of PLA2, COX1,
      or COX2. When Kupffer cells were treated with mepacrine to inhibit PLA2 (5575+/
      453 pg/ml), PGE2 production was not different from that by PVSal-treated controls
      (6467+/-614 pg/ml), but when Kupffer cells were incubated in the presence of the
      COX1 inhibitor flurbiprofen (3512+/-407 pg/ml) or the COX2 inhibitor nimesulide
      (2800+/-830 pg/ml), production was decreased 46.7% and 56.7%, respectively, over
      control activity without added inhibitor. PVT also increased Kupffer cells COX1
      and COX2 mRNA as measured by Northern blot. Heart transplants were then performed
      from Wistar-Furth donors into Lewis recipients at the time of PVT, SVT, PVSal, or
      PVT + indomethacin (COX1/2 inhibitor). PVT prolonged allograft survival (12.0+/
      0.9 days) compared with PVSal (6.3+/-0.3; P<0.01) or SVT (6.3+/-0.3; P<0.04).
      Indomethacin shortened graft survival when given with PVT (6.5+/-0.3 days). In
      summary, PVT increased Kupffer cell PGE2 production, up-regulated transcription
      of Kupffer cells COX1 and COX2 mRNA, and prolonged cardiac allograft survival.
      COX1/2 inhibition abrogated the effect of PVT. The results indicated that the
      immunosuppressive effect of PVT may be mediated by up-regulation of Kupffer cell
      COX1 and COX2. Manipulation of Kupffer cell arachidonic acid metabolism may be
      useful in augmentation of PVT-induced immunosuppression.

PMID- 9233714
TI  - Class I MHC mediates programmed cell death in human lymphoid cells.
AB  - BACKGROUND: Although signaling via class I MHC molecules has been shown to
      suppress T-cell responses, the mechanisms by which these effects are mediated
      have not been delineated. Studies were conducted to examine the possibility that
      5H7 (a murine anti-human mAb specific for the alpha3 domain of human class I MHC)
      induces programmed cell death (PCD). MATERIALS: Normal human T cells and
      lymphocyte tumor lines were used. PCD was assessed by viable cell recovery (VCR)
      with trypan blue, ethidium bromide/acridine orange staining, and terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling techniques. RESULTS:
      5H7 induced growth inhibition of lymphocyte tumor cell lines as assessed by
      [3H]thymidine incorporation. 5H7 also induced marked reductions in VCR of
      lymphocyte tumors and normal human T and B cells, with the most dramatic
      reductions occurring in B cells and B cell-derived tumors (JY, BeVD, and 521).
      Reductions in tumor growth observed with 5H7 monoclonal antibody, however, were
      not observed with other anti-human class I MHC monoclonal antibodies, TP2599
      (alpha3 domain specific) and W6/32 (alpha2/alpha3 domain specific). Cells treated
      with 5H7 demonstrated typical features of PCD including cytoplasmic
      vacuolization, DNA condensation, and apoptotic body formation. Reduction in VCR
      was augmented by anti-CD3 monoclonal antibody and was not reversed by exogenous
      interleukin 2. Induction of PCD was not observed with soluble 5H7 F(ab)'2
      fragments alone, but cross-linking of 5H7 F(ab)'2 fragments by F(ab)'2 fragments
      of human Ig-absorbed goat anti-mouse Ig partially restored PCD induction,
      indicating that anti-class I MHC monoclonal antibody can induce PCD in an FcR
      independent system and that monoclonal antibody cross-linking is necessary for
      PCD induction. CONCLUSIONS: These studies provide the first evidence that class I
      MHC molecules mediate PCD in human T and B cells.

PMID- 9233715
TI  - Noninvasive metabolic assessment of human donor livers: prognostic value of 31P
      magnetic resonance spectroscopy for early graft function.
AB  - BACKGROUND: The purpose of this study was to investigate whether phosphorus-31
      magnetic resonance spectroscopy (31P-MRS) of the isolated donor liver can serve
      as a viability indicator with prognostic value for transplantation outcome.
      METHODS: Forty human donor livers preserved with University of Wisconsin solution
      were studied shortly before transplantation. The respective spectral peak areas
      of the isolated donor liver were correlated with the amount of hepatocellular
      graft damage and liver metabolic function shortly after implantation. RESULTS:
      The individual phosphomonoesters, inorganic phosphate, phosphodiesters, and
      nicotine adenine dinucleotide peaks were not prognostic for postoperative
      hepatocellular damage or liver metabolic capacity. The presence of adenosine
      triphosphate, however, predicts a significantly better metabolic capacity to
      eliminate bilirubin, to synthesize fibrinogen and antithrombin III, and to
      maintain a better prothrombin time after transplantation. Furthermore, this study
      is probably the first 31P-MRS demonstration in the human liver of
      phosphocreatine. CONCLUSIONS: In the clinical setting described, metabolic
      assessment using 31P-MRS did not result in a reliable noninvasive test to predict
      primary graft dysfunction. Study of the role of phosphocreatine in liver
      metabolism during cold storage is needed.

PMID- 9233717
TI  - Chronically rejected rat kidney allografts induce donor-specific tolerance.
AB  - Previous studies on pathophysiological mechanisms of chronic graft rejection
      demonstrated the impact of both alloresponsiveness and nonspecific immunological
      events on the process. To study the role of alloantigen-specific factors further,
      we hypothesized an acceleration of chronic graft rejection after
      presensitization. Chronically rejected renal allografts in the established
      Fischer 344 --> Lewis rat model were replaced sequentially by native allografts
      of donor origin. Grafting of second allografts was performed 2, 4, 8, and 12
      weeks after the original transplantation and followed long term. Second
      allografts demonstrated significantly ameliorated functional and structural
      alterations with few cellular infiltrates. These changes were independent from
      the time interval between first and second engraftment (2-12 weeks);
      immunosuppressive treatment after the second engraftment was not influential. The
      nonresponsiveness was not restricted to the second kidney allografts, as heart
      allografts of donor origin in these recipients also functioned indefinitely,
      whereas third-party grafts (Lewis x Brown Norway F1) and Fischer 344 heart grafts
      in untreated Lewis control rats were acutely rejected. Thus, donor-specific and
      tissue-nonspecific graft acceptance is achieved by second engraftment of donor
      specific allografts in a model of chronic graft rejection. Those observations
      demonstrate the synergistic effects of alloresponsiveness and of the injured
      graft itself for the development of chronic graft failure.

PMID- 9233716
TI  - Murine interleukin 4 transgenic heart allograft survival prolonged with down
      regulation of the Th1 cytokine mRNA in grafts.
AB  - BACKGROUND: Data supporting the differential activation of T helper (Th) 2 cells
      in transplantation acceptance/tolerance in rodents have been presented by several
      investigators. However, the differential activation of Th2 cells may be simply
      the result of allograft acceptance/tolerance induction instead of a contribution
      to the maintenance of grafts. METHODS: Therefore, we established interleukin (IL)
      4 transgenic mice under the control of a cardiac alpha-myosin heavy chain
      promotor and transplanted IL-4-expressing heart allografts into unmodified
      recipients to determine the actual contribution of the Th2 bias to allograft
      acceptance. RESULTS: Among 16 newborn C57BL/6J (B6) mice, three were positive for
      the IL-4 transgene. Serum IL-4 levels of transgenic versus control B6xC3H F1 mice
      were not statistically different. Reverse-transcriptase polymerase chain reaction
      showed that the transgenic B6xC3H F1 mice expressed IL-4 mRNA in the heart and in
      the lung, whereas control mice did not express IL-4 in any organ. IL-4 mRNA
      expression in the transgenic but not in the control heart was also confirmed by
      RNAse protection assay and fluorescence in situ hybridization. The survival of IL
      4 transgenic B6xC3H heart grafts heterotopically placed in C3H recipients was
      prolonged compared with that of nontransgenic grafts (19.0+/-9.1 vs. 6.8+/-2.2
      days, P=0.003). Interferon-gamma mRNA expression in IL-4 transgenic heart grafts
      on the fifth posttransplant day as assessed by Northern blotting was suppressed
      compared with that in control grafts. Reverse-transcriptase polymerase chain
      reaction analysis showed that IL-2 mRNA was suppressed in the IL-4 transgenic
      grafts compared with that in control grafts, while IL-4 mRNA was observed only in
      IL-4 transgenic grafts. IL-10 mRNA was detected at similar levels in both
      transgenic and control grafts. CONCLUSIONS: A Th2 bias may contribute to
      allograft acceptance in part by inducing the down-regulation of Th1-cytokine
      mRNAs, but it may not be sufficient to induce indefinite graft survival.

PMID- 9233718
TI  - Conversion of recurrent delta-positive hepatitis B infection to seronegativity
      with famciclovir after liver transplantation.
AB  - BACKGROUND: Recurrent hepatitis B infection after liver transplantation is
      associated with poor graft and patient survival. Famciclovir is a nucleoside with
      virostatic action in hepatitis B infection. We report the case of a 51-year-old
      patient who developed recurrent delta-positive hepatitis B infection after liver
      transplantation. After famciclovir treatment, he became seronegative for
      hepatitis B early and hepatitis B surface antigens and developed protective anti
      hepatitis B surface antibody titers. METHODS: After recurrent hepatitis B was
      confirmed, treatment with famciclovir was initiated. RESULTS: Eighteen days after
      starting famciclovir, the patient became seronegative for hepatitis B early
      antigen and delta antigen, and hepatitis B virus DNA was no longer detectable in
      serum. Three months later, the patient became hepatitis B surface antigen
      negative and remains well 16 months later with increasing anti-hepatitis B
      surface levels. CONCLUSIONS: Antiviral treatment with famciclovir may be useful
      in treatment of delta-positive hepatitis B infection following liver
      transplantation. Further evaluation of famciclovir in treatment and prevention of
      hepatitis B in these patients is warranted.

PMID- 9233719
TI  - Effect of cilastatin on cyclosporine-induced acute nephrotoxicity in kidney
      transplant recipients.
AB  - BACKGROUND: Cyclosporine (CsA)-induced acute nephrotoxicity could be reduced by
      prevention of parenchymal accumulation of the drug itself. The objective of this
      prospective study was to evaluate whether cilastatin, an inhibitor of active
      tubular resorption of CsA, reduces CsA-induced acute nephrotoxicity in kidney
      graft recipients. METHODS: Sixty-nine kidney recipients with immediate graft
      functional recovery were randomly assigned to either the treatment group
      (imipenem/cilastatin, n=33) or the control group (ceftazidime, n=36). All
      patients followed a standard immunosuppressive regimen based on CsA and low-dose
      prednisone. Graft function and CsA levels were evaluated 3, 5, 10, 15, and 30
      days after transplantation. RESULTS: Compared with the control group,
      imipenem/cilastatin administration reduced the serum creatinine level in the
      first 2 weeks after transplantation, reaching a significant effect on
      postoperative day 10 (P<0.05). No significant differences were demonstrated
      between the two groups for CsA levels, patient and graft survival, and all the
      other examined parameters. CONCLUSIONS: Our findings support the hypothesis that
      cilastatin administration can reduce CsA-induced acute nephrotoxicity after
      kidney transplantation.

PMID- 9233720
TI  - Lung rejection occurs in lung transplant recipients with blood chimerism.
AB  - BACKGROUND: It has been postulated that chimerism after transplantation might
      promote graft acceptance. In the present study, we prospectively assessed blood
      chimerism in 10 lung transplant recipients during the first posttransplant year
      and investigated whether chimerism was associated with an immunologically stable
      situation of the graft. METHODS: The recipients' peripheral blood mononuclear
      cells were obtained before transplantation and at various time points during the
      first postoperative year. Donor cells were detected using nested polymerase chain
      reaction amplification of a donor-specific HLA-DRB1 allele. Clinical graft
      acceptance was determined by the number of rejection episodes. RESULTS: The
      incidence of blood chimerism was high during the first 3 postoperative months and
      then decreased over time. All patients experienced at least one acute rejection
      episode, and three patients developed chronic rejection. CONCLUSION: We, thus,
      conclude that rejection of the lung allograft may occur in the presence of blood
      chimerism.

PMID- 9233721
TI  - Dynamic analysis of hepatitis C virus polymorphism in patients with orthotopic
      liver transplantation.
AB  - BACKGROUND: The hepatitis C virus (HCV) quasispecies feature is important for HCV
      persistence. Most liver grafts are reinfected by HCV after liver transplantation
      (LTx). METHODS: The degree of HCV polymorphisms during LTx was determined by
      single-strand conformation polymorphism (SSCP) analysis and direct sequencing of
      the HCV hypervariable region 1 (HVR1). RESULTS: The number of HCV HVR1 SSCP bands
      in three patients decreased within 3 months after LTx as compared with before
      LTx. Direct sequencing of serial samples of one patient showed that the number of
      HVR1 polymorphic sites was lower at 1.5 months after LTx, and that the major
      sequence was identical to that before LTx. The number of both the HVR1 SSCP bands
      and the polymorphic sites after 3 months after LTx returned to a similar level as
      before LTx. CONCLUSIONS: Only a subset of the preexisting HCV variants replicates
      in the transplant liver graft. The limited immunological selective pressure
      within the first post-LTx period results in a homogenous HCV population that
      becomes more heterogenous after the first 3 months.

PMID- 9233722
TI  - CTLA4Ig attenuates accelerated rejection (presensitization) in the mouse islet
      allograft model.
AB  - BACKGROUND: Sensitization to donor antigens is a problem of growing magnitude in
      clinical transplantation. At a molecular level, this is due to the interaction
      between antigen bearing antigen-presenting cells and recipient T cells and
      involves both antigen presentation and co-stimulation. METHODS: Allogeneic islet
      transplantation was performed using DBA/2J donors and B6AF1 recipients. Four
      weeks before transplantation, recipient animals were given donor-specific
      transfusion (DST) alone, DST + CTLA4Ig, DST + control IgG, or no treatment. Graft
      loss was defined as a blood glucose >300 mg/100 ml. RESULTS: Administration of
      DST + control IgG 4 weeks before transplantation resulted in accelerated
      rejection due to presensitization (median survival time of 8 days, compared with
      14.5 days for the no-treatment group). Animals treated with CTLA4Ig in
      combination with DST had a median survival time of 12 days, compared with 8 days
      for DST + IgG. CONCLUSIONS: CTLA4Ig attenuates the tempo of accelerated rejection
      in this islet allograft model of presensitization, but does not prolong allograft
      survival as compared with no treatment.

PMID- 9233723
TI  - Transplantation-associated malignancies: restriction of human herpes virus 8 to
      Kaposi's sarcoma.
AB  - BACKGROUND: The human herpes virus 8 (HHV8) has been detected in all forms of
      Kaposi's sarcoma. HHV8 was also reported to be present in epithelial skin tumors
      of patients after renal transplantation, raising the question of the clinical
      relevance of HHV8 in transplant-related tumors. METHODS: Using a highly sensitive
      nested polymerase chain reaction assay, we analyzed for the presence of HHV8-DNA
      in the tumor tissue of renal transplant recipients with Kaposi's sarcoma (n=2)
      and non-Hodgkin's lymphomas (n=6), and in 32 tumors from 10 patients with
      multiple epithelial skin tumors. RESULTS: HHV8-DNA was detected in both cases of
      Kaposi's sarcoma but not in either the non-Hodgkin's lymphomas or the epithelial
      skin tumors. CONCLUSIONS: Our data confirm the association of HHV8 with Kaposi's
      sarcoma but not with other transplant-related tumors. Further studies are needed
      to analyze the risk for transmission of HHV8 by the donor and the possible
      exclusion of HHV8-positive patients as organ donors.

PMID- 9233724
TI  - Tissue-specific characteristics of cytotoxic graft-infiltrating T cells during
      renal allograft rejection.
AB  - BACKGROUND: The alloresponse after renal transplantation was studied using
      alloreactive T cells generated in vivo (from renal biopsies) and in vitro (from
      mixed kidney lymphocyte cultures). METHODS: Tissue specificity of graft
      infiltrating T cells (GIC) was investigated using donor-derived proximal tubular
      epithelial cells (PTEC) and splenocytes as targets in cytotoxicity assays.
      RESULTS: The outgrowth of cytotoxic T cells was associated with histologically
      proven interstitial rejection. GIC were categorized into four groups: (1) GIC
      cytotoxic for both PTEC and splenocytes (n=30), (2) noncytotoxic GIC (n=8), (3)
      GIC recognizing only splenocytes (n=1), and (4) GIC specifically recognizing PTEC
      (n=7). Similar tissue-specific T cells could be generated in vitro using mixed
      kidney lymphocyte cultures. Cytotoxicity of GIC from biopsies with moderate to
      severe rejection was CD8 independent, whereas cytotoxicity toward splenocytes was
      CD8 dependent. CONCLUSIONS: Our results show that polyclonal cytotoxic T-cell
      responses with tissue-specific characteristics are elicited during rejection
      episodes after renal transplantation.

PMID- 9233725
TI  - Sinus arrest during tacrolimus (FK506) and digitalis treatment in a bone marrow
      transplant recipient.

PMID- 9233726
TI  - Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment.

PMID- 9233727
TI  - Triage for patients with gastrointestinal hemorrhage: patients who don't need
      intensive care.

PMID- 9233728
TI  - Increased artificial deadspace for deliberate hypercapnia.

PMID- 9233729
TI  - You take the high mode and I'll take the low mode...for now.

PMID- 9233730
TI  - Ventilatory muscles and mechanical ventilatory support.

PMID- 9233731
TI  - Inotropic treatment and intestinal mucosal tissue oxygenation in a model of
      porcine endotoxemia.

PMID- 9233732
TI  - Avoiding the rush.

PMID- 9233733
TI  - Investigation of myasthenic crisis.

PMID- 9233735
TI  - Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase
      III, randomized, double-blind, placebo-controlled, multicenter trial. The
      Interleukin-1 Receptor Antagonist Sepsis Investigator Group.
AB  - OBJECTIVE: To determine the therapeutic efficacy and safety of recombinant human
      interleukin-1 receptor antagonist (rhIL-1ra) in the treatment of patients with
      severe sepsis. DESIGN: Prospective, randomized, double-blind, placebo-controlled,
      multicenter trial with a planned, midstudy, interim analysis. SETTING: Ninety-one
      academic medical center intensive care units in North America and Europe.
      PATIENTS: Patients with severe sepsis or septic shock (n = 696) received standard
      supportive care and antimicrobial therapy for sepsis, in addition to rhIL-1ra or
      placebo. INTERVENTIONS: Patients were randomized to receive either rhIL-1ra (100
      mg) or placebo (vehicle) by intravenous bolus, followed by a 72-hr continuous
      intravenous infusion of either rhIL-1ra (2.0 mg/kg/hr) or placebo. MEASUREMENTS
      AND MAIN RESULTS: The study was terminated after an interim analysis found that
      it was unlikely that the primary efficacy end points would be met. The 28-day,
      all-cause mortality rate was 33.1% (116/350) in the rhIL-1ra treatment group,
      while the mortality rate in the placebo group was 36.4% (126/346), yielding a 9%
      reduction in mortality rate (p = .36). The patients were well matched at the time
      of study entry; 52.9% of placebo-treated patients were in shock while 50.9% of
      rhIL-1ra-treated patients were in shock at the time of study entry (p = .30). The
      mortality rate did not significantly differ between treatment groups when
      analyzed on the basis of site of infection, infecting microorganism, presence of
      bacteremia, shock, organ dysfunction, or predicted risk of mortality at the time
      of study entry. No excess number of adverse reactions or microbial
      superinfections were attributable to rhIL-1ra treatment in this study.
      CONCLUSIONS: A 72-hr, continuous intravenous infusion of rhIL-1ra failed to
      demonstrate a statistically significant reduction in mortality when compared with
      standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has
      any therapeutic activity in severe sepsis, the incremental benefits are small and
      will be difficult to demonstrate in a patient population as defined by this
      clinical trial.

PMID- 9233736
TI  - BLEED: a classification tool to predict outcomes in patients with acute upper and
      lower gastrointestinal hemorrhage.
AB  - OBJECTIVE: To develop an outcome prediction tool (BLEED: ongoing bleeding, low
      systolic blood pressure, elevated prothrombin time, erratic mental status,
      unstable comorbid disease) for clinical use in patients with either acute upper
      or acute lower gastrointestinal (GI) hemorrhage. DESIGN: A cohort study. SETTING:
      Barnes Hospital and Jewish Hospital, two private university-affiliated teaching
      hospitals in St. Louis, MO. PATIENTS: Four hundred sixty-five patients with
      either acute upper or acute lower GI hemorrhage admitted from the emergency
      department. INTERVENTIONS: Admission of patients to the intensive care unit or
      hospital ward was determined by emergency department physicians, without use or
      knowledge of BLEED criteria. Patients meeting any BLEED criteria at their initial
      assessment in the emergency department were classified as "high-risk." All other
      patients were classified as "low-risk." MEASUREMENTS AND MAIN RESULTS: The main
      outcome measure was the occurrence of an inhospital complication, defined as
      recurrent GI hemorrhage, surgery to control the source of hemorrhage, and
      hospital mortality. Patients classified as high-risk had significantly greater
      rates of inhospital complications at both Barnes Hospital (relative risk, 2.47;
      95% confidence interval, 1.38 to 4.44; p < .001) and Jewish Hospital (relative
      risk, 8.94; 95% confidence interval, 3.92 to 20.41; p < .001) compared with
      patients classified as low-risk. Patients classified as high-risk at either
      hospital were significantly more likely to develop additional organ system
      derangements, require a greater number of transfused units of packed red blood
      cells, and have longer hospital stays compared with patients classified as low
      risk (p < .006). The BLEED classification also identified a greater frequency of
      intensive care admission for both low-risk (RR, 4.21; 95% Cl, 2.24 to 7.89) and
      high-risk (relative risk, 1.58; 95% confidence interval, 1.23 to 2.02) patients
      at Barnes Hospital compared with those patients at Jewish Hospital, although no
      beneficial effects on patient outcome were reported. CONCLUSIONS: The BLEED
      classification, applied at initial emergency department evaluation and before
      admission, predicts hospital outcomes for patients with acute upper or lower GI
      hemorrhage. This outcome prediction tool also identified variations in intensive
      care utilization between two hospitals.

PMID- 9233737
TI  - Serum neuron-specific enolase as early predictor of outcome after cardiac arrest.
AB  - OBJECTIVE: To examine the prognostic value of serum neuron-specific enolase for
      early prediction of outcome in patients at risk for anoxic encephalopathy after
      cardiac arrest. DESIGN: Prospective study. SETTING: Coronary intensive care unit
      of the University of Heidelberg. PATIENTS: Forty-three patients (66.8 +/- 12.7
      [SD] yrs, range 33 to 85) who had had either primary or secondary cardiac arrest,
      followed by cardiopulmonary resuscitation (CPR). INTERVENTIONS: Serial blood
      samples and clinical examinations. MEASUREMENTS AND MAIN RESULTS: Serum neuron
      specific enolase concentrations were determined after CPR on 7 consecutive days.
      Twenty-five patients remained comatose and subsequently died; 18 patients
      survived the first 3 months and had no relevant functional deficit at 3-month
      follow-up. Neuron-specific enolase concentrations were correlated with neurologic
      outcome. Concentrations of >33 ng/mL predicted persistent coma with a high
      specificity (100%) and a positive predictive value of 100%. Overall sensitivity
      was 80%, with a negative predictive value of 78%. Serum concentrations of neuron
      specific enolase exceeded this cutoff value no more than 3 days after cardiac
      arrest in 95% of patients in whom these concentrations had exceeded 33 ng/mL.
      CONCLUSIONS: In patients who have been resuscitated after cardiac arrest, serum
      neuron-specific enolase concentrations of >33 ng/mL predict persistent coma with
      a high specificity. Values below this cutoff level do not necessarily indicate
      complete recovery, because this method has a sensitivity of 80%.

PMID- 9233738
TI  - A comparison of cisatracurium (51W89) and atracurium by infusion in critically
      ill patients.
AB  - OBJECTIVE: To evaluate and compare the safety and efficacy of cisatracurium
      (51W89) and atracurium administered by continuous infusion to critically ill
      patients requiring neuromuscular blocking agents to facilitate mechanical
      ventilation. DESIGN: Open, randomized, multicenter study of patients receiving
      cisatracurium or atracurium infusion to facilitate mechanical ventilation.
      SETTING: Five university teaching hospital intensive care units in the United
      Kingdom. PATIENTS: Sixty-one adult patients requiring neuromuscular blocking
      agents to facilitate mechanical ventilation. INTERVENTIONS: Bolus doses followed
      by continuous infusions of cisatracurium or atracurium were administered. Onset,
      maintenance, and recovery of neuromuscular blockade were measured, using
      transcutaneous ulnar nerve stimulation and an accelerometer. MEASUREMENTS AND
      MAIN RESULTS: Forty patients received cisatracurium (mean duration 48.1 +/- 4.2
      [SEM] hrs), and 21 patients received atracurium (mean duration 46.1 +/- 5.8 hrs).
      The infusion rate for patients receiving cisatracurium was 3.1 +/- 0.2
      microg/kg/min, and for patients receiving atracurium 10.4 +/- 0.9 microg/kg/min.
      There were no significant differences in mean times to 70% recovery of Train-of
      Four ratio (cisatracurium 60 mins, atracurium 57 mins), although there was
      considerable interpatient variation (20 to 175 mins with cisatracurium vs. 35 to
      85 mins with atracurium). One patient who received cisatracurium exhibited
      intermittent bronchospasm during and after the study period. CONCLUSIONS:
      Cisatracurium, an isomer of atracurium, appears to be a suitable agent for
      providing muscle relaxation in critically ill patients.

PMID- 9233739
TI  - Low levels of nitric oxide as contaminant in hospital compressed air: physiologic
      significance?
AB  - OBJECTIVES: To determine whether the levels of nitric oxide found in hospital
      compressed air have a clinically relevant effect on oxygenation in intubated
      patients with normal lungs. DESIGN: Prospective study. SETTING: Cardiothoracic
      and surgical intensive care unit in a university hospital. PATIENTS: Twelve
      postoperative patients receiving mechanical ventilation. INTERVENTIONS: Pure
      nitrogen and oxygen were substituted for hospital compressed air as a source of
      blending for correct FIO2. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and PaO2
      were measured in nitrogen and oxygen used for blending oxygen during stable FIO2
      levels. Inhaled nitric oxide was measured with a nitric oxide-chemiluminescence
      detector. There was no clinically relevant change in systemic hemodynamics.
      However, the PaO2 decreased significantly when nitrogen was used for blending.
      Inhaled nitric oxide levels varied from 2 to 550 parts per billion during use of
      hospital compressed air; no nitric oxide was detectable during use of nitrogen.
      CONCLUSIONS: The low concentration of nitric oxide in hospital compressed air
      improves oxygenation in patients with normal lungs receiving mechanical
      ventilation.

PMID- 9233740
TI  - Effects of clonidine on prolonged postoperative sympathetic response.
AB  - OBJECTIVE: Surgical trauma results in diffuse sympathoadrenal activation which is
      thought to contribute to perioperative cardiovascular complications in high-risk
      patients. Regional anesthetic and analgesic techniques can attenuate this "stress
      response" and reduce the occurrence rate of adverse perioperative events;
      however, their use in the postoperative period is logistically difficult and
      costly. The present study was undertaken to evaluate whether transdermal
      administration of the alpha2 adrenergic-receptor agonist, clonidine, can be used
      as a pharmacologic means of blunting the stress response throughout the
      perioperative period. DESIGN: Double-blind, placebo-controlled clinical trial in
      patients undergoing pancreatico-biliary surgery. SETTING: Operating rooms and
      surgical intensive care unit of a major university teaching hospital. PATIENTS:
      Forty patients scheduled for major upper abdominal surgery. INTERVENTIONS:
      Patients received either clonidine (0.2 mg orally and a clonidine TTS-3 patch the
      evening before surgery and 0.3 mg orally on call to the operating room) or
      matched oral and transdermal placebo. MEASUREMENTS AND MAIN RESULTS: Heart rate,
      systemic arterial blood pressure, plasma catecholamine, clonidine, interleukin-6
      concentrations, and 24-hr urine cortisol and nitrogen excretion were measured the
      day before surgery and daily thereafter for 72 hrs postoperatively. Preoperative
      transdermal (and oral) clonidine administration resulted in therapeutic plasma
      clonidine concentrations throughout the perioperative period (1.54 +/- .07 [SEM]
      microg/mL). Clonidine reduced preoperative epinephrine and norepinephrine
      concentrations by 65%. Plasma catecholamine concentrations increased in both
      groups following surgery but were markedly lower throughout the postoperative
      period in patients receiving clonidine. Patients receiving clonidine had a
      reduced frequency rate of postoperative hypertension. Clonidine had no effect on
      plasma interleukin-6 concentration, urine cortisol excretion, or urine nitrogen
      excretion. No adverse effects of clonidine administration were observed.
      CONCLUSIONS: The combined administration of oral and transdermal clonidine
      effectively attenuated the catecholamine response to surgical stress throughout
      the postoperative study period. Clonidine administration produced specific
      sympatholytic effects, since other elements of the stress response were not
      attenuated. Undesirable side effects were not noted. The sustained sympatholytic
      effects we observed suggest that alpha2 adrenergic-receptor agonists may offer a
      pharmacologic means of modifying the sympathoadrenal response to injury, and may
      be useful in reducing perioperative complications.

PMID- 9233741
TI  - Extracorporeal circulation increases nitric oxide-induced methemoglobinemia in
      vivo and in vitro.
AB  - OBJECTIVES: Methemoglobinemia is a well-known side effect of nitric oxide
      inhalation. We tested the hypothesis whether cardiopulmonary bypass increases
      methemoglobin formation by nitric oxide. DESIGN: A two-phase study: a) a
      controlled, prospective in vivo study of inhaled nitric oxide treatment followed
      by b) a second, prospective and controlled in vitro study. SETTING: Pediatric
      intensive care unit and research laboratory in a university hospital. PATIENTS:
      The in vivo study consisted of 25 patients following open-heart surgery and 19
      children with acute respiratory distress syndrome (ARDS) or persistent pulmonary
      hypertension of the newborn. The in vitro study consisted of 20 patients with and
      20 patients without cardiopulmonary bypass. INTERVENTIONS: For the in vivo study,
      methemoglobin measurements were taken before and after application of 20 parts
      per million (ppm) of nitric oxide. For the in vitro study, red blood cells of
      patients were incubated with 32 ppm nitric oxide before and after surgery.
      Methemoglobin, glutathione, adenosine triphosphate (ATP), and nicotinamide
      adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADHP)
      concentrations were compared. MEASUREMENTS AND MAIN RESULTS: For the in vivo
      study, nitric oxide inhalation increased methemoglobin from 0.2 +/- 0.1% to 1.2
      +/- 0.7% in patients receiving nitric oxide after open-heart surgery and from 0.2
      +/- 0.1% to 0.5 +/- 0.4% in ARDS/persistent pulmonary hypertension of the newborn
      patients (p < .01). For the in vitro study, nitric oxide incubation of red blood
      cells increased methemoglobin concentration from 3.7 +/- 1.9% preoperatively to
      7.4 +/- 2.4% after open-heart surgery. This increase was not observed in patients
      who did not undergo cardiopulmonary bypass (3.6 +/- 1.6% vs. 3.6 +/- 1.9%; p <
      .001). In erythrocytes of patients undergoing extracorporeal circulation, there
      was no difference between pre- and postoperative glutathione, ATP, and NADH/NADPH
      concentrations. CONCLUSIONS: Cardiopulmonary bypass is an important risk factor
      for methemoglobinemia when inhaled nitric oxide is applied. This risk is not
      secondary to diminished concentrations of energetic substrates.

PMID- 9233742
TI  - Relationship between behavioral and physiological indicators of pain, critical
      care patients' self-reports of pain, and opioid administration.
AB  - OBJECTIVES: To examine the accuracy of inferences about critical care patients'
      pain based on physiological and behavioral indicators and to assess the
      relationship between registered nurse and patient pain scores and doses of
      opioids administered. DESIGN: Descriptive, comparative analysis. SETTING: Three
      intensive care units and two postanesthesia care units in two hospitals.
      SUBJECTS: Fourteen critical care nurses who conducted 114 pain assessments on 31
      surgical patients. INTERVENTIONS: Nurses used a pain assessment and intervention
      notation algorithm that contained lists of behavioral and physiological
      indicators of pain to make inferences about a patient's pain intensity. Fourteen
      registered nurses completed up to five pain assessments on each patient over a 4
      hr period. Following both the physiological and behavioral ratings, nurses rated
      the patients' pain intensity, using a 0 to 10 numeric rating scale, and they
      asked patients to provide a self-report of pain intensity, using a similar
      numeric rating scale. Nurses then administered an intravenous dose of an opioid
      from a sliding scale prescription. MEASUREMENTS AND MAIN RESULTS: Moderate-to
      strong correlations were found between the number of behavioral indicators at
      times 1 through 5 and between the number of physiological indicators and nurses'
      ratings of the patients' pain intensity at times 1 through 4 (p < .05). Although
      nurses' pain ratings were consistently lower than patients' pain ratings across
      the five time points, these differences were not significant. The amount of
      opioid analgesic administered by the nurse correlated more frequently with
      nurses' pain ratings than with patients' self-reports of pain intensity.
      CONCLUSIONS: The use of a detailed, standardized pain assessment and intervention
      notation algorithm that incorporates behavioral and physiological indicators may
      assist healthcare professionals in making relatively accurate assessments of a
      patient's pain intensity. Further research is needed to determine the specific
      decision-making processes and criteria that healthcare professionals use to
      choose doses of analgesics to administer to critically ill patients.

PMID- 9233743
TI  - Noninvasive estimation of right ventricular systolic pressure in postinfarction
      ventricular septal rupture: an assessment of two Doppler echocardiographic
      methods.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of Doppler echocardiography in the
      assessment of right heart hemodynamics and the diagnosis of pulmonary
      hypertension in patients with ventricular septal rupture due to acute myocardial
      infarction. DESIGN: A prospective, echocardiographic and right-heart
      catheterization study. SETTING: Medical intensive care unit (ICU) of a university
      hospital. PATIENTS: Twelve consecutive patients admitted to the ICU with the
      diagnosis of ventricular septal rupture in the setting of acute myocardial
      infarction. Confirmation of diagnosis was made during surgery (11 patients) or by
      autopsy (one patient). INTERVENTIONS: All patients were examined by two
      dimensional and Doppler echocardiography on admission and subsequently underwent
      bedside right-heart catheterization. MEASUREMENTS AND MAIN RESULTS: After
      identification and localization of the rupture site by two-dimensional
      echocardiography and/or color flow Doppler mapping, the maximal flow velocity of
      the transseptal jet was measured by continuous-wave Doppler and was used to
      calculate the peak interventricular pressure gradient by the modified Bernoulli
      equation. This value was subtracted from the systolic arterial blood pressure
      value to estimate right ventricular systolic pressure. The values obtained
      correlated well with catheter-derived measurements (r2 = .71; p = .001).
      Furthermore, in eight (67%) patients, right ventricular systolic pressure could
      also be determined by Doppler interrogation of the tricuspid regurgitant jet.
      Direct comparison of the results of the two echocardiographic methods yielded a
      good correlation (r2 = .66; p = .016). CONCLUSION: Doppler examination of the
      transseptal and tricuspid regurgitant jets is applicable to patients with
      ventricular septal rupture for rapid, noninvasive prediction of right ventricular
      hemodynamics.

PMID- 9233744
TI  - Increased artificial deadspace ventilation is a safe and reliable method for
      deliberate hypercapnia.
AB  - OBJECTIVES: To develop a simple method in an animal model to achieve deliberate
      hypercapnia, which can be used easily and safely to regulate the pulmonary
      vascular resistance without changing mean airway pressure and compromising
      oxygenation. DESIGN: Prospective study, with each animal used as its own control.
      SUBJECTS: Minipigs, weighing 11 to 14 kg (n = 7). INTERVENTIONS: A quadrilumen
      thermodilution pulmonary artery catheter was placed in minipigs via the internal
      jugular vein. Systemic blood pressure was measured with use of a femoral arterial
      catheter. The animals' lungs were ventilated with an FIO2 of 1.0, and a stable
      state of eucapnia was achieved and maintained for 30 mins. The artificial
      deadspace was increased every 30 mins, by connecting 45-mL (3- to 4-mL/kg)
      corrugated tube segments until a total deadspace volume of 180 mL was added.
      MEASUREMENTS AND MAIN RESULTS: Hemodynamic performance was evaluated at baseline
      and after 45 mL (3 to 4 mL/kg), 90 mL (6 to 8 mL/kg), 135 mL (9 to 11 mL/kg), and
      180 mL (12 to 15 mL/kg) of added deadspace. Data were indexed to the animal's
      weight (in kg). Increased artificial deadspace produced a significant (p < .05)
      increase in PaCO2. These increases in PaCO2 were associated with significant (p <
      .05) increases of 23%, 32%, 45%, and 46% in the mean pulmonary vascular
      resistance values, and 6%, 16%, 23%, and 23% in the mean pulmonary arterial
      pressure, respectively. The systemic pH was decreased from a mean baseline value
      of 7.45 to 7.39, 7.28, 7.20, and 7.11, respectively. There were no significant
      changes in PaO2, oxygen consumption, systemic vascular resistance, and cardiac
      output throughout the experiments. CONCLUSIONS: A gradual increase in artificial
      deadspace ventilation produces a state of deliberate hypercapnia. In our animal
      model, a moderate increase in artificial deadspace significantly increased the
      pulmonary vascular resistance but was not associated with detrimental respiratory
      acidemia. Larger volumes of added artificial deadspace had no detrimental effect
      on cardiac output, oxygen content, oxygen consumption, and systemic vascular
      resistance, but were associated with significant respiratory acidemia and
      therefore should be avoided.

PMID- 9233745
TI  - Partial liquid ventilation: a comparison using conventional and high-frequency
      techniques in an animal model of acute respiratory failure.
AB  - OBJECTIVE: To test the hypothesis that high-frequency ventilation (HFV), when
      compared with conventional techniques, enhances respiratory gas exchange during
      partial liquid ventilation (PLV). DESIGN: A four-period crossover design.
      SETTING: Animal research laboratory of Children's Health Care-St. Paul. SUBJECTS:
      Thirty-two newborn piglets, weighing 1.40 +/- 0.39 kg. INTERVENTIONS: Animals
      were divided into four groups of eight animals: a) PLV with high-frequency jet
      ventilation; b) PLV with jet ventilation using a background intermittent
      mandatory ventilation (IMV) rate; c) PLV with high-frequency oscillation; or d)
      PLV with high-frequency flow interruption using a background IMV rate. After
      anesthesia, paralysis, and tracheotomy, a normal saline wash procedure produced
      lung injury. Perfluorocarbon was then instilled via the endotracheal tube in an
      amount estimated to represent functional residual capacity. Animals received
      randomly either PLV using conventional techniques or PLV using the selected HFV
      technique as initial treatment. Then, animals were crossed over to the
      alternative treatment at equal mean airway pressure, as measured at the
      endotracheal tube tip. This sequence was repeated for a total of four crossover
      periods, such that all animals were treated twice with PLV using conventional
      techniques and twice with PLV using HFV. MEASUREMENTS AND MAIN RESULTS: We
      measured airway pressures at the endotracheal tube tip, aortic and central venous
      blood pressures, arterial blood gases, and respiratory system mechanics at
      baseline, after induction of lung injury, and at specified intervals throughout
      the experiment. Measurements were made before and 15 mins after crossovers, then
      ventilators were adjusted to normalize gas exchange. Measurements were again made
      30 mins later, at the end of the treatment period. All types of PLV provided
      adequate gas exchange. Only PLV using jet ventilation with IMV produced gas
      exchange equal to that seen during PLV using conventional techniques at
      equivalent mean airway pressure. By the end of the treatment periods, only PLV
      using high-frequency oscillation continued to require higher airway pressure than
      PLV using conventional techniques for equivalent gas exchange. CONCLUSIONS: Gas
      exchange was not enhanced during PLV-HFV. Application of HFV with PLV provides no
      clear acute physiologic advantages to PLV using more conventional techniques.

PMID- 9233746
TI  - Effects of prolonged controlled mechanical ventilation on diaphragmatic function
      in healthy adult baboons.
AB  - OBJECTIVE: To study diaphragmatic strength and endurance after a prolonged period
      of mechanical ventilation. DESIGN: Prospective animal study. SETTING: Animal
      research laboratory. SUBJECTS: Seven uninjured adult baboons (Papio cynocephalus)
      were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated.
      Animals were monitored with pulmonary arterial and peripheral arterial catheters.
      INTERVENTIONS: Mechanical ventilation was provided for 11 days with an FIO2 of
      0.21 and tidal volume of 15 mL/kg. Pulmonary function tests, including lung
      volumes, arterial blood gases, and chest radiographs were also monitored. Nursing
      care procedures included frequent turning, chest physiotherapy, and endotracheal
      suction. Antacids and prophylactic antibiotics (intravenous penicillin, topical
      polymyxin B, and gentamicin sulfate) were administered. In three animals,
      fishhook electrodes were surgically placed around both phrenic nerves on both day
      0 and after 11 days of mechanical ventilation for diaphragmatic stimulation. On
      day 0, the electrodes were removed after phrenic nerve stimulation studies were
      performed. After 11 days of mechanical ventilation, animals were electively
      killed and full autopsy performed. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and
      pulmonary function parameters were measured at baseline and every day during the
      11 days of mechanical ventilation. Diaphragmatic strength and endurance were
      measured on days 0 and 11. Diaphragmatic endurance was determined by an
      inspiratory resistive loading protocol. There were no significant changes in
      hemodynamics, lung volumes, or gas exchange during the period of mechanical
      ventilation. On day 7, the chest radiographs showed patchy lobar atelectasis in
      six animals, which cleared by day 11 in all but two of the animals. Lung
      pathology showed mild, focal pneumonitis. By day 11, maximum transdiaphragmatic
      pressure had decreased by 25% from day 0 and diaphragmatic endurance had
      decreased by 36%. CONCLUSIONS: Eleven days of mechanical ventilation and
      neuromuscular blockade in healthy baboons resulted in nonsignificant changes in
      hemodynamics, oxygenation, and/or lung function. However, significant impairment
      in diaphragmatic endurance and strength were seen. Based on these results, it is
      likely that prolonged mechanical ventilation by itself impairs diaphragmatic
      function independent of underlying lung disease.

PMID- 9233747
TI  - Inotropic treatment and intestinal mucosal tissue oxygenation in a model of
      porcine endotoxemia.
AB  - OBJECTIVE: To evaluate the dose-related effects of dopamine, dopexamine, and
      dobutamine on intestinal mucosal tissue oxygenation following short-time infusion
      of Escherichia coli lipopolysaccharide, which has previously been shown to
      decrease mucosal tissue oxygenation by 60% of control values. DESIGN:
      Prospective, randomized, unblinded study. SETTING: Animal research laboratory.
      SUBJECTS: Anesthetized, mechanically ventilated domestic pigs. INTERVENTIONS:
      Pigs were infused with 2 microg/kg of E. coli lipopolysaccharide over 20 mins via
      the superior mesenteric artery. Pulmonary artery occlusion pressure was
      maintained near 15 mm Hg, using a mixed infusion regimen of Ringer's lactate
      solution and hydroxyethyl starch. Following endotoxemia, a small segment of the
      jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. The
      control group (n = 7) received no further interventions. Pigs in the dopamine (n
      = 7), dopexamine (n = 7), and dobutamine (n = 7) groups were infused with 2.5, 5,
      10, and 20 microg/kg/min of the respective drug via a central venous catheter.
      MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics as well as systemic,
      mesenteric, and femoral blood gas variables were measured using an arterial, a
      thermodilution pulmonary artery, a superior mesenteric venous, and a femoral
      venous catheter. Jejunal mucosal tissue PO2 was measured by means of two Clark
      type surface oxygen electrodes. Oxygen saturation of jejunal mucosal
      microvascular hemoglobin was determined by tissue reflectance spectrophotometry.
      Infusion of endotoxin resulted in pulmonary hypertension. Systemic hemodynamics
      remained unchanged except for brief decreases in cardiac output and arterial
      blood pressure. Dopamine, dopexamine, and dobutamine increased systemic oxygen
      delivery in a dose-related manner by 80% (p < .01), 96% (p = .00), and 129% (p =
      .00) of values before inotropic treatment. Dopamine increased mucosal tissue PO2
      by 109% (10-microg dose, p < .01) and 164% (20-microg dose, p = .00), and mucosal
      hemoglobin oxygen saturation by 61% (5-microg dose, p < .05), 102% (10-microg
      dose, p < 01) and 121% (20-microg dose, p = .00). Dopexamine increased mucosal
      tissue PO2 by 89% (20-microg dose, p < .01) and mucosal hemoglobin oxygen
      saturation by 26% (2.5-microg dose, p < .05) and 35% (5-, 10-, and 20-microg
      dose, p < .05). In the dobutamine and control groups, no significant effect on
      either mucosal tissue PO2 or hemoglobin oxygen saturation was observed.
      CONCLUSIONS: In this model of porcine endotoxemia, dopamine and, to a lesser
      extent, dopexamine increase intestinal mucosal tissue oxygenation. Of all three
      inotropes used, dobutamine has the most pronounced effect on systemic oxygen
      delivery, but it does not improve mucosal tissue oxygenation. Selective
      vasodilation within the intestinal mucosa, mediated mainly by dopamine-1
      receptors, seems to explain the observed intestinal mucosal effect of dopamine
      and dopexamine.

PMID- 9233748
TI  - Dietary fish oil and fish and borage oil suppress intrapulmonary proinflammatory
      eicosanoid biosynthesis and attenuate pulmonary neutrophil accumulation in
      endotoxic rats.
AB  - OBJECTIVE: Proinflammatory eicosanoids and cytokines are important mediators of
      local inflammation in acute lung injury. We determined if enteral nutrition with
      anti-inflammatory fatty acids, eicosapentaenoic acid, and gamma-linolenic acid
      would reduce the intrapulmonary synthesis of proinflammatory eicosanoids and
      cytokines and pulmonary neutrophil accumulation in a rat model of acute lung
      injury. DESIGN: Prospective, randomized, controlled, double-blind study. SETTING:
      Research laboratory at a university medical center. SUBJECTS: Male Long-Evans
      rats (250 g). INTERVENTIONS: Rats were randomly assigned to three dietary
      treatment groups and fed nutritionally complete diets (300 kcal/kg/day)
      containing 55.2% of the total calories from fat with either 97% corn oil, 20%
      fish oil, or 20% fish and 20% borage oil for 21 days. On day 22, bronchoalveolar
      lavage was performed 2 hrs after an intravenous injection of Salmonella
      enteritidis endotoxin (10 mg/kg) or saline. Bronchoalveolar lavage fluid was
      analyzed for leukotriene B4, leukotriene C4/D4, thromboxane B2, prostaglandin E2,
      6 keto-prostaglandin F1alpha, tumor necrosis factor (TNF)-alpha, and macrophage
      inflammatory protein-2 (MIP-2). Lung myeloperoxidase activity (a marker for
      neutrophil accumulation) and phospholipid fatty acid composition were also
      determined. MEASUREMENTS AND MAIN RESULTS: Lung phospholipid concentrations of
      arachidonic acid were lower and the concentrations of eicosapentaenoic acid and
      docosahexaenoic acid were higher with fish oil and fish and borage oil as
      compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and
      elongated intermediate of gamma-linolenic acid, increased with fish and borage
      oil as compared with fish oil and corn oil. The levels of leukotriene B4,
      leukotriene C4/D4, 6-keto-prostaglandin F1alpha, and thromboxane B2 with corn oil
      were significantly increased with endotoxin as compared with saline. In contrast
      to the corn oil group, endotoxin did not significantly increase bronchoalveolar
      lavage levels of leukotriene B4, leukotriene C4/D4, and thromboxane B2 above
      those of saline-treated rats with fish oil and fish and borage oil. Lung
      myeloperoxidase activity was significantly increased in endotoxin-treated rats
      compared with those rats given saline in all dietary treatment groups. However,
      lung myeloperoxidase activity was significantly lower with either fish oil or
      fish and borage oil as compared with corn oil after endotoxin. Although endotoxin
      increased the levels of TNF-alpha and MIP-2 with all dietary treatment groups as
      compared with saline-treated rats, there were no significant differences in the
      levels of either cytokine between the dietary treatment groups. CONCLUSIONS:
      These results indicate that dietary fish oil and fish and borage oil as compared
      with corn oil may ameliorate endotoxin-induced acute lung injury by suppressing
      the levels of proinflammatory eicosanoids (but not TNF-alpha or MIP-2) in
      bronchoalveolar lavage fluid and reducing pulmonary neutrophil accumulation.

PMID- 9233749
TI  - Arginine, glutamine, and dehydroepiandrosterone reverse the immunosuppressive
      effect of prednisone during gut-derived sepsis.
AB  - OBJECTIVE: Corticosteroids are used broadly in clinical practice but may
      profoundly impair resistance to infections. In contrast, arginine and glutamine
      are safe and effective immunonutrients that can improve resistance to infection
      in both animals and humans. This study assessed whether arginine and/or
      glutamine, with or without dehydroepiandrosterone, a natural endogenous steroid,
      could reverse the susceptibility to infection caused by prednisone in a burned
      animal model. DESIGN: Prospective, randomized study. SETTING: A laboratory
      approved by the American Association for the Accreditation of Laboratory Animal
      Care at the Shriners Burns Institute, Cincinnati Unit. SUBJECTS: Adult female
      Balb/c mice, weighing 18 to 22 g. INTERVENTIONS: Animals were prefed an arginine-
      and/or glutamine- or a glycine-supplemented diet for 14 days.
      Dehydroepiandrosterone (25 mg/kg/day) and/or prednisone (10 mg/kg/day) were given
      on days -4 to 0 before animals were given a gavage of 10(9) 111indium-oxine
      radiolabeled or -unlabeled Escherichia coli and 20% total body surface area burn
      injury. Survival rate and the extent of translocation of E. coli were determined.
      MEASUREMENTS AND MAIN RESULTS: Feeding with diets supplemented with arginine,
      glutamine, and arginine plus glutamine and treatment with dehydroepiandrosterone
      reversed the susceptibility to infections caused by prednisone and burn injury.
      The beneficial effects were mediated by enhanced killing of translocated bacteria
      and/or by an improved gut barrier function. CONCLUSIONS: Dietary supplementation
      can reverse the susceptibility to infections caused by prednisone. Both arginine
      and glutamine as well as dehydroepiandrosterone may be useful therapeutic agents
      for preventing infections in steroid-treated patients.

PMID- 9233750
TI  - Experimental fat embolism induces urine 2,3-dinor-6-ketoprostaglandin F1alpha and
      11-dehydrothromboxane B2 excretion in pigs.
AB  - OBJECTIVE: To evaluate the in vivo production of prostacyclin and thromboxane A2
      during the initial phase of experimental fat embolism as assessed, respectively,
      by determinations of urine 2,3-dinor-6-ketoprostaglandin F1alpha and 11
      dehydrothromboxane B2 excretion. DESIGN: Randomized, controlled trial. SETTING:
      Animal laboratory. SUBJECTS: Twenty seven domestic pigs, weighing 24 to 31 kg.
      INTERVENTIONS: All pigs were anesthetized and mechanically ventilated during the
      experiment. Eighteen pigs were subjected to an intracaval infusion of 10%
      allogeneic bone marrow suspension at a dose of 100 mg/kg over 5 mins. Nine pigs
      received only bone marrow suspension (fat embolism group). Nine pigs were given
      an intravenous bolus of aspirin (300 mg) 1 hr before the bone marrow suspension
      infusion. After the induction of fat embolism, intravenous aspirin was
      administered at a dose of 150 mg/hr for 2 hrs (aspirin-treated group). Nine pigs
      were infused with saline (control group). MEASUREMENTS AND MAIN RESULTS: In the
      fat embolism group, cardiac index decreased within 30 mins, while mean arterial
      pressure remained unchanged. Central venous pressure and pulmonary artery
      occlusion pressure remained relatively stable over time in the animals with fat
      embolism. Mean pulmonary arterial pressure and pulmonary vascular resistance
      increased immediately after the bone marrow suspension infusion from 23 +/- 0.8
      (SEM) to 34 +/- 1.3 mm Hg and from 305 +/- 28 to 585 +/- 45 dyne x sec/cm5,
      respectively; these variables remained increased throughout the study period.
      Simultaneously, pulmonary shunt in the fat embolism group increased persistently
      from the baseline of 12.3 +/- 2.8%, and reached its maximum of 26.1 +/- 4.8% at
      the end of the experiment. Instant and gradual decreases in PaO2 (from 95 +/- 4
      to 67 +/- 5 torr [12.6 +/- 0.5 to 8.9 +/- 0.7 kPa]), hemoglobin oxygen saturation
      (from 97.2 +/- 0.4 to 91.8 +/- 1.8%), and oxygen delivery (from 16.3 +/- 1.0 to
      12.6 +/- 0.4 mL/min/kg) were observed in the fat embolism group. In the bone
      marrow suspension-infused animals, urine 2,3-dinor-6-ketoprostaglandin F1alpha
      excretion increased transiently from 451 +/- 63 up to 1466 +/- 499 pg/micromol
      creatinine, while urine 11-dehydrothromboxane B2 excretion increased transiently
      from 385 +/- 36 up to 2307 +/- 685 pg/micromol creatinine. In the aspirin-treated
      animals, urinary excretion of these prostanoid metabolites was reduced by 81% and
      88%, respectively. The changes in mean pulmonary arterial pressure and PaO2 were
      ameliorated, and the alterations in pulmonary shunt and SaO2 were abolished in
      the animals with aspirin treatment. CONCLUSIONS: Pulmonary hypertension,
      increased pulmonary vascular tone, and increased pulmonary shunt are hallmarks of
      the present fat embolism model. These hemodynamic responses may, at least partly,
      be related to the changed balance between prostacyclin and thromboxane A2
      production.

PMID- 9233751
TI  - Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in
      porcine endotoxic shock.
AB  - OBJECTIVE: To determine the effects of the stable prostacyclin analog, iloprost,
      in a porcine model of endotoxin-induced mesenteric ischemia. DESIGN: Prospective,
      experimental, randomized, controlled study. SETTING: Animal research laboratory
      at a university medical center. INTERVENTIONS: Pigs were randomized to receive a
      constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of
      carrier solution (normal saline) 30 mins before being infused with endotoxin (100
      microg/kg over 1 hr). The infusion with iloprost or carrier solution was
      continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS:
      Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy
      during which a magnetic flowprobe was placed around the superior mesenteric
      artery and an ileal tonometer was inserted. Thirty minutes before they were
      infused with endotoxin, the animals were randomized to receive intravenous
      iloprost or normal saline. Endotoxin was infused centrally over a 60-min period.
      Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the
      start of the endotoxin infusion. Data were measured at the end of the endotoxin
      infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by
      the dosage of iloprost used in this experiment. After resuscitation, the cardiac
      output returned to baseline in the iloprost-treated group but remained decreased
      in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric
      blood flow increased 34% above baseline levels in animals pretreated with
      iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was
      significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7
      kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44
      +/- .23) in the control group than in the iloprost-treated group. CONCLUSIONS:
      Pretreatment with intravenous iloprost effectively increased intestinal blood
      flow in this model of endotoxin-induced mesenteric ischemia. This action of the
      drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose
      iloprost had no effect on mean arterial pressure, it may be a useful adjunct in
      the treatment of sepsis and septic shock.

PMID- 9233752
TI  - Therapy of myasthenic crisis.
AB  - OBJECTIVES: To investigate the frequency, causes, and characteristic features of
      the course of isolated myasthenic crisis (defined as acute respiratory failure
      with the need for mechanical ventilation). To compare the effectiveness of three
      different therapeutic regimens (i.e., continuous intravenous infusion of
      pyridostigmine, pyridostigmine plus prednisolone, and plasma exchange) in terms
      of duration of ventilation and outcome of patients with myasthenic crisis.
      DESIGN: Population-based retrospective study covering the period 1970 to 1995.
      SETTING: University hospital, center for myasthenia gravis in Saxony, Germany.
      PATIENTS: Of 235 patients with myasthenia gravis treated at our institution, 44
      patients developed a total of 63 myasthenic crises (average annual incidence
      2.5%). INTERVENTIONS: Myasthenic crises were treated with pyridostigmine (n =
      24), pyridostigmine plus prednisolone (n = 18), and plasma exchange (n = 21).
      MEASUREMENTS AND MAIN RESULTS: There were no significant differences between the
      three treatment groups with respect to clinical characteristics, duration of
      mechanical ventilation, complications, and outcome on release from intensive care
      and after 3 months. Eleven (17%) patients had severe cardiac arrhythmia, which
      ended fatally for six patients. CONCLUSIONS: None of the therapeutic regimens
      applied demonstrated any advantage over the others. All three regimens used were
      found to be effective and should be applied depending on the circumstances
      prevailing. Patients with myasthenic crisis must undergo careful cardiac
      monitoring, and temporary pace-making should be provided where clinically
      indicated.

PMID- 9233753
TI  - Dose response, recovery, and cost of doxacurium as a continuous infusion in
      neurosurgical intensive care unit patients.
AB  - OBJECTIVES: To determine the optimal dosing of doxacurium as a continuous
      infusion in neurosurgical patients with traumatic brain injury; to determine the
      effects of bolus administration of doxacurium on heart rate (HR), blood pressure
      (BP), and intracranial pressure (ICP); to monitor neuromuscular recovery after
      discontinuation of prolonged doxacurium infusion; and to compare the cost of
      doxacurium with other current neuromuscular blocking drugs. DESIGN: Prospective,
      open-label study. SETTING: Neurosurgical intensive care unit (ICU) of a
      university-affiliated teaching hospital. PATIENTS: Eight critically ill,
      mechanically ventilated patients with traumatic head injury and normal renal and
      hepatic function. Patients had ICP monitoring. INTERVENTIONS: A bolus injection
      of doxacurium (0.05 mg/kg) followed by a continuous infusion (0.015 mg/kg/hr),
      adjusted to maintain one twitch during Train-of-Four nerve stimulation of the
      adductor pollicis muscle. MEASUREMENTS AND MAIN RESULTS: Bolus injections of
      doxacurium did not alter the HR, BP, or ICP. Patients were paralyzed 66 +/- 12
      (SEM) hrs, with recovery of the fourth twitch occurring 118 +/- 19 mins after
      infusion of the doxacurium was discontined. There were no incidences of prolonged
      weakness, myopathy, or other adverse events. CONCLUSIONS: Continuous infusion of
      doxacurium provides stable neuromuscular blockade for neurosurgical patients with
      traumatic brain injury. Doxacurium is devoid of clinically important interactions
      with HR, BP, or ICP and is less costly than other neuromuscular blockers used in
      the ICU.

PMID- 9233754
TI  - Noninvasive capnometry monitoring for respiratory status during pediatric
      seizures.
AB  - OBJECTIVE: To determine the reliability and clinical value of end-tidal CO2 by
      oral/nasal capnometry for monitoring pediatric patients presenting post ictal or
      with active seizures. DESIGN: Clinical, prospective, observational study.
      SETTING: University affiliated children's hospital. INTERVENTIONS: One hundred
      sixty-six patients (105 patients with active seizures, 61 post ictal patients)
      had end-tidal CO2 obtained by oral/nasal sidestream capnometry, and respiratory
      rates, oxygen saturation, and pulse rates recorded every 5 mins until 60 mins had
      elapsed. End-tidal CO2 values were compared with a capillary PCO2 and clinical
      observation. MEASUREMENTS AND MAIN RESULTS: The mean end-tidal CO2 reading was
      43.0 +/- 11.8 torr [5.7 +/- 1.6 kPa] and the mean capillary PCO2 reading was 43.4
      +/- 11.7 torr [5.7 +/- 1.6 kPa]. The correlation between end-tidal CO2 and
      capillary PCO2 was significant (r2 = .97; p < .0001). A relative average bias of
      0.33 torr (0.04 kPa) with end-tidal CO2 lower than capillary PCO2 was established
      with 95% limits of agreement +/-4.2 torr (+/-0.6 kPa). Variability of difference
      scores was not related to range of mean scores (r2 = .00003), age (r2 = .0004),
      or respiratory rates (r2 = .0009). End-tidal CO2 (r2 = .22; p < .001) correlated
      better with respiratory rate changes when compared with oxygen saturation (r2 =
      .02; p = .01). CONCLUSIONS: Dependable end-tidal CO2 values can be obtained in
      pediatric seizure patients using an oral/nasal cannula capnometry circuit.
      Continuous end-tidal CO2 monitoring provides the clinician with a reliable
      assessment of pulmonary status that can assist with decisions to provide
      ventilatory support.

PMID- 9233755
TI  - Sulfoconjugation and renal excretion contribute to the interpatient variation of
      exogenous catecholamine clearance in critically ill children.
AB  - OBJECTIVE: To delineate the contributions of sulfoconjugation, renal excretion,
      and patient age to the wide interpatient variability in exogenous dobutamine and
      dopamine plasma clearance. DESIGN: Simultaneous plasma free and sulfoconjugated
      dobutamine and/or dopamine, respective urine free catecholamine, and serum
      creatinine were determined on stable critically ill children receiving unchanged
      continuous infusions of dobutamine and/or dopamine for at least 1 hr. Free
      dobutamine and dopamine clearance rates were calculated. SETTING: Pediatric and
      neonatal intensive care units in university settings. PATIENTS: Forty-seven
      stable critically ill neonates and children. INTERVENTIONS: Continuous infusions
      of dobutamine and/or dopamine: nine patients received dopamine only, 27 patients
      received dobutamine only, and 11 patients received both simultaneously.
      MEASUREMENTS AND MAIN RESULTS: Fractions of plasma dobutamine and dopamine
      sulfoconjugated were 0.73 +/- 0.05 and 0.76 +/- 0.05, respectively. Free plasma
      dobutamine and dopamine clearances were 102 +/- 15 mL/kg/min and 250 +/- 38
      mL/kg/min, respectively. Linear regression analyses demonstrated relationships of
      the fraction of plasma dobutamine and dopamine sulfoconjugated to the respective
      free plasma clearances (r2 = .30, p < .01, and r2 = 0.29, p < .01, respectively),
      and, more impressively, to the natural logarithm of the respective free plasma
      clearances (r2 = 0.58, p < .001, and r2 = 0.39, p < .01). Patients with serum
      creatinine concentrations >2 mg/dL had lower free plasma dobutamine and dopamine
      clearance rates than those patients with serum creatinine of <2 mg/dL (6 +/- 1
      vs. 107 +/- 15 mL/kg/min for dobutamine and 40 +/- 38 vs. 270 +/- 39 mL/kg/min
      for dopamine, respectively, p < .05 for both by Mann-Whitney U test). No
      relationship was noted between free catecholamine clearance and age. CONCLUSION:
      Sulfoconjugation and renal excretion are important determinants of the wide
      interpatient variability in plasma free dobutamine and dopamine clearance rates.

PMID- 9233756
TI  - Failure of the INVOS 3100 cerebral oximeter to detect complete absence of
      cerebral blood flow.

PMID- 9233757
TI  - Partial liquid ventilation enhances surfactant phospholipid synthesis.

PMID- 9233758
TI  - Mechanical ventilation management of asthma.

PMID- 9233759
TI  - P53 associates with trk tyrosine kinase.
AB  - The p53 tumor suppressor gene encodes a phosphoprotein which when overexpressed
      can induce growth arrest at the G1 and G2/M phases of the cell cycle, promote
      differentiation and apoptosis. This paper demonstrates that p53 can associate
      with trk tyrosine kinase. Expression of a murine temperature-sensitive (ts) p53
      mutant in PC12 cells overexpressing trk (a model system to analyse cellular
      differentiation and signal transduction induced by NGF) induces morphological
      changes in the absence of NGF stimulation at 32 degrees C but not at 37 degrees
      C. In cells differentiated by p53, trk, but not EGFr, was hyperphosphorylated on
      tyrosine. Furthermore trk was not phosphorylated when expressed in Saos-2 cells
      (human osteosarcoma cells that lack expression of both endogenous trk and p53) at
      either temperature. However, transfection of ts p53 into these cells induces trk
      phosphorylation at 32 degrees C in the absence of NGF stimulation. Association of
      trk and p53 can be detected in NIH3T3 and PC12 cells co-expressing trk and the ts
      p53 mutant, in NIH3T3 and PC12 cells transfected with trk alone, and in
      untransfected PC12 cells, showing that overexpressed and/or endogenous trk
      associates with endogenous, low levels of p53. These data suggest a novel
      function for p53 which involves the stimulation of signal transduction pathways
      (mediating morphological properties of cells), possibly through association with
      and hyperphosphorylation of trk.

PMID- 9233760
TI  - Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53
      and suppresses transformed cell growth.
AB  - The E6 proteins originating from the tumour-associated Human Papillomavirus (HPV)
      types 16 and 18 have been shown to bind to and target the tumour suppressor
      protein, p53, for ubiquitin-mediated degradation. However, in cell lines derived
      from cervical neoplasias, the predominant early region transcripts are spliced
      and encode truncated forms of E6, termed E6*. We report here that HPV-18 E6*
      protein will interact both with the full-length E6 proteins from HPV-16 and HPV
      18 and also with E6-AP, and subsequently blocks the association of full length E6
      protein with p53. We also show that, as a result of this block, E6* can inhibit
      E6-mediated degradation of p53 both in vitro and in vivo. The biological
      consequences of this are increased transcriptional activity on p53-responsive
      promoters and an inhibition of cell growth in cells transfected with E6*. This is
      the first report of a potential biological function for this polypeptide and may
      represent a means by which HPV is able to modulate the activity of the full
      length E6 protein with respect to p53 during viral infection.

PMID- 9233761
TI  - Activation of the focal adhesion kinase signal transduction pathway in cervical
      carcinoma cell lines and human genital epithelial cells immortalized with human
      papillomavirus type 18.
AB  - The inappropriate activation of protein-tyrosine kinases (PTKs) has been
      associated with initiation and progression of several types of human cancers. We
      therefore postulated that immortalization by DNA tumor viruses results in the
      induction of PTKs fundamental to these processes. An RT-PCR-based screen was thus
      used to identify PTKs that were abundantly expressed in HPV-18-immortalized
      epithelial cells and HPV-containing carcinoma cell lines. One of the genes
      isolated in this screen was the focal adhesion kinase (FAK; pp125FAK), a
      cytoplasmic protein kinase that is activated in v-src transformed cells or by
      stimulation with mitogenic polypeptides. FAK also becomes catalytically active
      upon integrin engagement with extracellular matrix proteins, such as fibronectin.
      We found that FAK expression and activity were significantly elevated in HPV-18
      E6/E7-immortalized human genital epithelial cells relative to their primary cell
      counterparts. Protein expression and tyrosine phosphorylation of the putative FAK
      substrate, paxillin, were also notably increased upon HPV-18 immortalization of
      genital epithelial cells and in HPV-containing cervical carcinoma cell lines.
      Most significantly, these cells expressed markedly higher levels of both
      intracellular and extracellular fibronectin, thus providing a mechanism for
      activation of FAK and increased tyrosine phosphorylation of paxillin. These
      findings suggest a role for the integrin/FAK-mediated signaling pathway in
      cervical carcinogenesis and represent one of the first demonstrations of a
      tyrosine kinase whose activity is elevated following viral immortalization.

PMID- 9233762
TI  - Epstein-Barr virus latent membrane protein does not inhibit differentiation and
      induces tumorigenicity of human epithelial cells.
AB  - Latent membrane protein (LMP) is a latent Epstein-Barr virus (EBV) protein
      expressed in the EBV associated malignancy, nasopharyngeal carcinoma (NPC).
      Properties ascribed to this protein include inhibition of epithelial cell
      differentiation and deregulation of epithelial cellular gene expression, and are
      believed to contribute to the development of NPC. Studies to evaluate the
      oncogenic potential of LMP in epithelial cells have not been conclusive. We
      carried out studies to determine the tumorigenic activity of LMP in two human
      epithelial cell lines, SCC12F and HaCaT; while SCC12F LMP transfectants were non
      tumorigenic in severe combined immunodeficient mice, HaCaT LMP transfectants were
      strongly oncogenic. The tumours produced were well differentiated, keratinising
      squamous cell carcinomas suggesting that LMP does not inhibit epithelial cell
      differentiation which conflicts with a previous report by Dawson et al. (1990).
      To resolve this discrepancy we examined the ability of HaCaT and SCC12F LMP
      transfectants to differentiate in a suspension culture assay. Both lines were
      able to differentiate to a similar extent as parental lines and control
      transfectants. Our results indicate that LMP is strongly oncogenic in human
      epithelial cells but that inhibition of differentiation is not necessarily a
      mechanism by which LMP contributes to the pathogenesis of NPC.

PMID- 9233763
TI  - Involvement of caspase-4(-like) protease in Fas-mediated apoptotic pathway.
AB  - Proteases of the caspase family, especially caspase-1 (ICE)(-like), caspase-3
      (CPP32/Yama/apopain)(-like) and caspase-8 (MACH/FLICE/Mch5) proteases, are
      implicated in Fas (APO-1/CD95)-mediated apoptosis. Here, we show that the caspase
      4 (TX/ICH-2/ICE(rel)II)(-like) protease, another member of the caspase family, is
      also involved in Fas-mediated apoptosis, based upon the observations: (i) caspase
      4 is processed in response to an agonistic anti-Fas antibody treatment, (ii)
      overexpression of a mutant caspase-4 with active site mutations in both p20 and
      p10 subunits delays Fas-mediated apoptosis, (iii) microinjected anti-caspase-4
      antibodies inhibit Fas-mediated apoptosis. Together with our observations that
      the mutant caspase-4 inhibits the Fas-mediated activation of caspase-3(-like)
      proteases and purified caspase-4 cleaves pro-caspase-3 to generate a subunit of
      active form, these results suggest that Fas-mediated apoptosis is driven by a
      caspase cascade in which the caspase-4(-like) protease transmits a death signal
      from caspase-8 to caspase-3(-like) proteases probably through directly cleaving
      pro-caspase-3(-like) proteases.

PMID- 9233764
TI  - Inhibition of E2F-4/DP-1-stimulated transcription by p202.
AB  - The interferon (IFN)-inducible proteins mediate activities of the interferons
      including the cell growth-regulatory activity. We have shown that p202, an IFN
      inducible 52kDa primarily nuclear phosphoprotein whose expression in transfected
      cells inhibits cell proliferation, interacts with the retinoblastoma tumor
      suppressor protein (pRb) and the transcription factor E2F (E2F-1/ DP-1) in vitro
      and in vivo. p202 was shown to inhibit E2F-1/DP-1-stimulated transcription of a
      reporter gene and of endogenous genes. Here we report that expression of p202
      inhibited E2F-4/DP-1-stimulated transcription of a reporter gene in transfected
      cells. Furthermore, this inhibition was associated with the inhibition of the
      sequence-specific DNA-binding of E2F-4 both in complex with the pocket proteins
      p107 or p130 and in its 'free' form in vitro. p202 bound to p107 and p130 in
      vitro and in vivo and also associated with E2F-4, supporting the notion that
      complexes containing p107/E2F-4 or p130/ E2F-4 and p202 exist in vivo. Moreover,
      cotransfection of E2F-4-encoding plasmid in AKR-2B cells overcame p202-mediated
      inhibition of cell growth, raising the possibility that p202 contributes to cell
      growth inhibition by the interferons, at least in part, by modulating E2F-4
      mediated transcription.

PMID- 9233765
TI  - In vivo regulation of single copy and amplified N-myc in human neuroblastoma
      cells.
AB  - Amplification with subsequent overexpression of N-myc is a recurrent genomic
      alteration of neuroblastoma cells. DMS-in-vivo-footprinting of the basal promoter
      of the human N-myc gene (positions -221 to +21) revealed three changes in
      promoter architecture that are clustered in a 50 bp region and included (1)
      protein binding to two overlapping E2F-sites, (2) extreme hypersensitivity of
      guanine - 159, and (3) a short stretch of single stranded DNA with a single
      protected guanine. While in transient assays the basal promoter activated gene
      expression in all cell lines analysed, the changes at the endogenous promoter
      were restricted to neuroblastoma cells with strong N-myc expression. The
      hypersensitivity of guanine -159 could result from protein binding to a flanking,
      evolutionary conserved 5'-CCTCCC-3'-element, referred to as CT-box, that was
      bound in vitro in a Zn2+-requiring manner by a protein from nuclear extracts of
      neuroblastoma cells. Four copies of the CT-box in front of an N-myc minimal
      promoter (-60 to + 18) activated expression of a reporter gene in transient
      transfections whereas four copies of the mutant element did not. Our data add N
      myc to a growing list of mammalian genes with CT-boxes that bind proteins in a
      Zn2+-dependent manner. Moreover, the data suggest that a common mechanism
      controls N-myc expression in neuroblastomas irrespective of N-myc copy number,
      and that in cell lines with amplification all gene copies contribute to N-myc
      expression.

PMID- 9233766
TI  - Bistable biochemical switching and the control of the events of the cell cycle.
AB  - Some of the events of the cell cycle appear to be triggered by a bistable
      mechanism. A bistable biochemical system can respond to a small, slow signal and
      is carried by positive feedback from one stable steady state directly to another,
      in an all-or-none manner. Slow or subthreshold stimuli do not cause accommodation
      or loss of excitability. Switching is not readily reversible by removing the
      stimulus, i.e. there is hysteresis: reversal generally requires a stronger,
      opposite stimulus. Biochemically, bistable biochemical switching requires
      positive feedback, and mechanisms for stabilizing the system against premature
      activation and for destabilization in response to a biological signal. Three
      bistable biochemical models, all suggested by reported experimental observations,
      are described and analysed. These models suggest that a titratable inhibitor may
      play an important part in bistable switching, because the end-point of titration
      can form a natural threshold for enhancement of positive feedback.

PMID- 9233767
TI  - Partial characterization of the woodchuck tumor suppressor, p53, and its
      interaction with woodchuck hepatitis virus X antigen in hepatocarcinogenesis.
AB  - Full length cDNAs for p53 were made by reverse transcription-polymerase chain
      reaction of total RNA from two normal woodchuck livers. Two randomly chosen
      clones from each liver were sequenced and shown to be identical. This sequence
      revealed 80% or more identity with p53 sequences from human, monkey, and mouse.
      The cDNA was translated into a 55 kD protein in vitro that was immunoprecipitated
      by antibodies to p53. Cotranslation of woodchuck p53 with woodchuck hepatitis
      virus X antigen, followed by immunoprecipitation suggested X/p53 complex
      formation. Similar complexes were also immunoprecipitated from extracts of
      infected liver, but not from uninfected liver. The finding of X/p53 complexes in
      vivo and in vitro in the woodchuck hepadnavirus system, combined with analogous
      data with hepatitis B, suggests a common mechanism by which these viruses
      contribute to hepatocellular transformation.

PMID- 9233768
TI  - p53-mediated accumulation of hypophosphorylated pRb after the G1 restriction
      point fails to halt cell cycle progression.
AB  - This study analyses whether the inability of p53 to induce G1 arrest after the
      restriction point relates to an inability to modulate pRb phosphorylation.
      Transient p53 overexpression in normal human diploid fibroblasts and p53
      deficient cancer cells led to increased levels of the cyclin-dependent kinase
      inhibitor p21 cip1/Waf1/Sdi1 and an accumulation of hypophosphorylated pRb in
      cells growing asynchronously and in cells synchronized in late G1 or M.
      Similarly, gamma-irradiation of asynchronous, late-G1, or S phase fibroblasts led
      to an increase in hypophosphorylated pRb. Experiments with fibroblasts expressing
      the HPV16 E6 protein indicated that accumulation of hypophosphorylated pRb
      required functional p53. Progression into and through S phase was not altered by
      the presence of hypophosphorylated pRb in late G1, consistent with the failure of
      p53 to mediate G1 arrest in cells that are past the restriction point. These data
      indicate that accumulation of hypophosphorylated pRb has significantly different
      effects on cell cycle progression in early G1 versus late G1 or S phase.

PMID- 9233769
TI  - Bcl-2 and Hsp27 act at different levels to suppress programmed cell death.
AB  - Apoptosis and necrosis, two morphologically distinct forms of cell death, can be
      induced by common stimuli depending on the doses and the cell type. This study
      compares the protective effect of oncoprotein Bcl-2 and of the small stress
      protein Hsp27 on these two types of cell death. We use rat embryo fibroblasts
      conditionally immortalized by the tsA58 mutant of SV40 large T antigen as
      parental cells to develop cell lines carrying inducible bcl-2 or hsp27 genes. Two
      apoptotic stimuli were used: shift to the restrictive temperature that induced
      p53-mediated apoptosis and treatment with low doses of hydrogen peroxide.
      Necrosis was induced by high doses of hydrogen peroxide. Although Bcl-2 and Hsp27
      protect these cells from necrotic death, only Bcl-2 appears capable of preventing
      apoptotic death. Bcl-2 protection is not mediated by a negative effect on the
      induction of the p53 responsive genes bax or waf1 but it slows down at least two
      stages of apoptosis: decrease of mitochondrial membrane potential and subsequent
      morphological changes. In contrast, although Hsp27 has been recently shown to
      inhibit apoptosis induced by various stimuli, its overexpression has no effect on
      apoptosis in this cell system. It should be also noticed that the apoptotic
      stimuli (temperature shift or hydrogen peroxide treatment) induce Hsp27, but not
      Bcl-2 accumulation suggesting that, in parental cells, Hsp27 might already
      provide some protection. However, taken together these results suggest that
      Hsp27, as well as Bcl-2, acts at several levels to inhibit cell death, but that
      their protective functions only partially overlap.

PMID- 9233770
TI  - Somatic mutations in the human homologue of Drosophila patched in primitive
      neuroectodermal tumours.
AB  - The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant
      disorder characterized by multiple developmental defects and cancer
      susceptibility, in particular to basal cell carcinomas (BCCs). Medulloblastomas,
      primitive neuroectodermal tumours (PNETs) arising in childhood, occur in about 3
      5% of NBCCS patients and a subset of PNETs was previously found with allelic
      imbalance at 9q22-q23, the region containing the gene for NBCCS (PTCH). We have
      analysed tumour DNA samples from 37 unrelated patients with sporadic PNETs and
      five medulloblastoma cell lines for PTCH mutations using an exon-by-exon single
      strand conformation polymorphism assay. We found three missense mutations, which
      affect conserved residues in transmembrane domains of the gene product and in the
      extracellular loop implicated in binding sonic hedgehog, one 2 bp deletion and an
      exon skipping splice site mutation. Most mutations were associated with the
      absence of the wild-type allele and were found in tumours exhibiting loss of
      heterozygosity (LOH) at loci flanking PTCH. The finding of LOH at 9q22-q23 in
      most mutated tumours while present in only three out of 26 tumours, in which a
      mutation was not identified, implicates PTCH as the target gene in PNETs with LOH
      at 9q22-q23 and deficient PTCH in the development of a subset of these tumours.
      Since all observed mutations were absent in the germ-line, a sporadic
      medulloblastoma developing as the first symptom of NBCCS is likely to be a very
      uncommon event.

PMID- 9233771
TI  - The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped to 6p12.3
      p21.1, the locus for cleidocranial dysplasia.
AB  - PEBP2/CBF is a heterodimeric transcription factor composed of alpha and beta
      subunits. There are at least three closely related genes, PEBP2alphaA/Cbfa1,
      AML1/PEBP2alphaB/Cbfa2 and PEBP2alphaC/Cbfa3, encoding the alpha subunit and one
      beta subunit encoding gene. Structural alterations of AML1 and the beta subunit
      gene by chromosome translocations are frequently associated with several types of
      human leukemia. Structural changes of any of these gene products would have
      potential to affect the function of others. In this study, we isolated the human
      PEBP2alphaA cDNA by which we mapped the gene to 6p12.3-p21.1. Human chromosome
      6p21 is the locus for cleidocranial dysplasia, an autosomal dominant bone
      disease. Recent gene disruption study revealed that PEBP2alphaA/Cbfa1 plays an
      essential role in osteogenesis (Komori et al., Cell, 1997, in press). Therefore,
      a close relationship between human PEBP2alphaA/CBFA1 and this bone disease is
      strongly implicated.

PMID- 9233772
TI  - A giant protein that stimulates guanine nucleotide exchange on ARF1 and Rab
      proteins forms a cytosolic ternary complex with clathrin and Hsp70.
AB  - We have recently identified an unusually large human protein that stimulates
      guanine nucleotide exchange on ARF1 and Rab proteins (EMBO J 15: 4262-4273,
      1996). This protein, designated p532 based on its predicted molecular weight
      (EMBO J 15: 5738, 1996), contains multiple structural domains including two
      regions of seven internal repeats highly related to the cell cycle regulator
      RCC1, a guanine nucleotide exchange factor for the small GTP-binding protein Ran,
      seven beta-repeat domains characteristic of the beta subunit of heterotrimeric G
      proteins, three putative SH3 binding sites, a putative leucine-zipper and a
      carboxy-terminal HECT domain characteristic of E3 ubiquitin-protein ligases. Some
      of these domains are known to be involved in protein-protein interactions,
      suggesting the existence of p532-interacting proteins. To identify some of these
      proteins, we used the carboxy-terminal RCC1-like domain (RLD) of p532 in the
      yeast two-hybrid system. We report here the isolation of a clone that encodes the
      last 654 amino acid residues of the clathrin heavy chain. This interaction
      involves amino acid residues 1315-1557 of the clathrin heavy chain and the
      carboxy, but not the amino-terminal RLD of p532. p532 has been located in the
      cytosolic fraction as well as in the Golgi apparatus. The interaction between
      p532 and clathrin only occurs in the cytosol and is mediated by the formation of
      an ATP-dependent ternary complex with the heat shock protein, Hsp70. These
      observations suggest that p532 is involved in membrane transport processes.

PMID- 9233773
TI  - Cloning and characterization of APS, an adaptor molecule containing PH and SH2
      domains that is tyrosine phosphorylated upon B-cell receptor stimulation.
AB  - Stimulation of B lymphocytes through their antigen receptor (BCR) results in
      rapid increases in tyrosine phosphorylation of a number of proteins, which leads
      to a cascade of biochemical changes that initiates B cell proliferation and
      differentiation or growth inhibition. A novel cDNA, designed APS, encoding an
      adaptor protein with a Pleckstrin homology (PH) domain, Src homology 2 (SH2)
      domain, and a tyrosine phosphorylation site was cloned from a B cell cDNA library
      using a yeast two hybrid system. APS is structurally similar to SH2-B, an SH2
      protein that potentially binds to the immunoreceptor tyrosine-based activation
      motif (ITAM) as well as Lnk which is postulated to be a signal transducer that
      links T-cell receptor to phospholipase Cgamma, Grb2 and phosphatidylinositol 3
      kinase. APS expressed only in human Burkitt's lymphoma cells among cell lines we
      examined and tyrosine phosphorylated in response to BCR stimulation. APS bound to
      Shc irrespective of stimulation and bound to Grb2 after stimulation, suggesting
      that it plays a role in linkage from BCR to Shc/Grb2 pathway. These results
      indicate that APS, SH2-B and Lnk form a new adaptor family that links immune
      receptors to signaling pathways involved in tyrosine-phosphorylation.

PMID- 9233774
TI  - Proliferation of chicken neuroretina cells induced by v-src, in vitro, depends on
      activation of the E2F transcription factor.
AB  - Quiescent chicken or quail retina neuroblasts (NR) can be induced to proliferate
      actively, in culture, by the v-src oncoprotein. The chE2F-1 transcription factor,
      a physiological partner of the retinoblastoma gene product, is highly expressed
      in vivo, in dividing chicken neuroretina cells (CNR). It is sharply down
      regulated as cells enter the post-mitotic differentiation stage, thus suggesting
      that E2F activity is a prerequisite for NR cell proliferation. In the present
      paper, transient expression assays of different forms of chE2F-1 were used to
      investigate the function of E2F for switching CNR cells from a quiescent to a
      proliferative state in vitro. Attempts to substitute the effects of v-src by an
      ectopic expression of E2F-1 were unsuccessful. However, in the same conditions,
      E2F-1 supports full growth of CEF in serum-depleted medium. Deletion mutants of
      E2F-1, with potential dominant-negative properties, were transfected in RSV
      infected CNR cells. One of these truncated mutants induces a G1 phase block in
      RSV-transformed CNR cells indicating that, although E2F-1 overexpression cannot
      overcome the cell proliferation block of post-mitotic CNR cells E2F-1, activity
      is an important component of the growth signal pathway delivered by v-src in
      these nervous cells.

PMID- 9233775
TI  - Transcriptional and post-transcriptional regulation of kappaB-controlled genes by
      pp60v-src.
AB  - The CEF-4/9E3 gene is expressed aberrantly in chicken embryo fibroblasts
      transformed by the Rous sarcoma virus. This aberrant expression is dependent on
      transcriptional activation and on the stabilization of the CEF-4 mRNA. The
      characterization of the CEF-4 promoter indicated that three distinct regulatory
      elements corresponding to an AP-1 binding site, a PRDII/ kappaB domain and a CAAT
      box are involved in the activation by pp60v-src. Several v-src responsive genes
      are controlled by AP-1 and members of the Ets family but few appear to be
      dependent on NF-kappaB. In this study we characterize the expression of genes
      regulated by NF-kappaB in normal and RSV-transformed CEF. Run-on transcription
      analysis indicated that pp60v-src induces the transcription of several genes
      controlled by NF-kappaB but at different levels. While the transcription of CEF-4
      was strongly stimulated, that of NF-kappaB1, c-rel, p53 or IkappaB-alpha was
      activated more modestly by pp60v-src. In addition the CEF-4 mRNA was the only
      mRNA species to accumulate significantly in transformed CEF. The ectopic
      expression of RelA or Rel resulted in the stimulation of the transcription of
      several known targets of NF-kappaB. However, the mRNA for IkappaB-alpha was the
      only mRNA species to accumulate considerably in the RelA- or Rel-expressing
      cells. Hence for most kappaB-controlled genes, transcriptional activation was not
      sufficient to obtain a significant increase in mRNA expression. Likewise, RelA or
      Rel enhanced the transcription of the CEF-4 gene without a significant
      accumulation of the CEF-4 mRNA. However, transformation by v-src caused a massive
      accumulation of the CEF-4 mRNA but not of other mRNA species in the RelA- and Rel
      expressing cells. Transient expression assays, run-on transcription and Northern
      blotting analyses indicated that the effect of pp60v-src on CEF-4 expression was
      mediated predominantly at the post-transcriptional level in these cells.
      Therefore transcriptional and post-transcriptional mechanisms determine the
      restricted pattern of activation of kappaB-controlled genes in RSV-transformed
      CEF.

PMID- 9233776
TI  - hMLH1 expression and cellular responses of ovarian tumour cells to treatment with
      cytotoxic anticancer agents.
AB  - Loss of expression of the hMLH1 and hPMS2 subunits of the MutL alpha-mismatch
      repair complex is a frequent event (9/10) in independent cisplatin resistant
      derivatives of a human ovarian carcinoma cell line. However, only hMLH1 mRNA is
      decreased in these MutL alpha-deficient lines. No alterations in the levels of
      the hMSH2 and hMSH6 (GTBP) subunits of the MutS alpha-complex are observed. An
      increase in the proportion of ovarian tumours negative for the hMLH1 subunit is
      observed in samples taken at second look laparotomy after chemotherapy (36%:
      4/11), compared to untreated tumours (10%: 4/39). No significant difference is
      observed for hMSH2, hMSH6 or hPMS2. Furthermore, cisplatin and doxorubicin
      resistant ovarian lines deficient in hMLH1 expression are cross-resistant to 6
      thioguanine and the methylating agent N-methyl-N-nitrosourea (MNU). Depletion of
      O6-alkylguanine-DNA-alkyltransferase (ATase) activity confers only limited
      increased sensitivity to MNU. Thus the mismatch repair deficient lines retain DNA
      damage tolerance even after ATase depletion. The hMLH1 deficient lines also lose
      ability to engage G1 and G2 cell cycle arrest after cisplatin damage. Together
      these data suggest that loss of hMLH1 expression may be a high frequency event
      following exposure of ovarian tumour cells to cisplatin and may be critically
      involved in the development of drug resistance. Thus, the hMLH1 status of these
      cells appears to be highly correlated with the ability to engage cell death and
      cell cycle arrest after DNA damage induced by cisplatin.

PMID- 9233777
TI  - Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast
      cancer cells.
AB  - Raf-1 protein serine/threonine kinase has been implicated in growth and damage
      responsive signal transduction pathways. Several reports indicate an important
      role of Ras protein in the growth factor-induced activation of Raf-1. Here we
      investigated the possible involvement of Ras in ionizing radiation-induced
      activation of Raf-1. Irradiation of MDA-MB 231 human breast cancer cells caused
      an increase in GTP-binding and hydrolysis on Ras, and co-immunoprecipitations of
      endogenous Grb2 with Sos and Raf-1 with Ras. An increase in the level of membrane
      bound Raf-1, and tyrosine-phosphorylation of Raf-1 were observed after
      irradiation. Consistent with these changes, irradiation of cells stimulated the
      catalytic activity of Raf-1. Finally, radiation treatment of breast cancer cells
      led to an increase in the phosphorylation and activity of the mitogen-activated
      protein kinase. Based on these biochemical modifications in vivo, we conclude
      that Raf-1 functions as an effector of Ras in the radiation-responsive signal
      transduction pathway leading to the activities of Raf-1 and mitogen-activated
      protein kinase.

PMID- 9233778
TI  - Resistance to p53-mediated growth arrest and apoptosis in Hep 3B hepatoma cells.
AB  - Mutations in the tumor suppressor p53 are a common event in hepatocellular
      carcinoma (HCC). Because HCCs typically occur in livers with chronic injury and
      impaired function, we have explored the role of wild-type p53 in regulating the
      growth and differentiation of Hep 3B hepatoma cells, a p53-negative line derived
      from a liver cancer. Stable Hep 3B cell lines were generated in which inducible
      p53 was introduced using either a temperature-sensitive mutant (p53val135) or a
      tamoxifen-regulated p53-estrogen receptor chimera (p53-mERtm-pBabepuro). In both
      cell lines, induction of transcriptionally active p53 was confirmed by assessing
      several p53 targets: Mdm2 protein, p21waf1 mRNA and protein, and the cyclin G
      promoter. Despite marked induction of p21waf1, cells with active p53 failed to
      undergo growth arrest, which is probably due to the presence of a non-functional
      retinoblastoma protein (pRb) in these cells. Apoptosis also was not observed,
      even after prolonged (48 h) serum starvation or exposure to cisplatinum. Lack of
      apoptosis was correlated with unchanged bax mRNA levels following p53 induction.
      Additionally, albumin mRNA levels remained unchanged, and there was no change in
      basal transactivation of a reporter containing the promoter of the haptoglobin
      gene, encoding an acute phase protein. This suggests that growth arrest may be
      required to promote liver-specific gene expression. Overall, our data demonstrate
      that introduction of transcriptionally active p53 does not alter the malignant,
      dedifferentiated phenotype of Hep 3B hepatoma cells. Hence, not all cancer cells
      are equally responsive to the re-activation of wild-type 53. The ability of a
      cancer cell to undergo p53-mediated phenotypic alterations may depend on the
      retention of functional downstream effector pathways.

PMID- 9233779
TI  - Induction of tyrosine phosphorylation and association of beta-catenin with EGF
      receptor upon tryptic digestion of quiescent cells at confluence.
AB  - Normal human breast epithelial (HBE) cells which reached confluence ceased growth
      and tightly adhered to each other, forming a monolayer. In quiescent cells thus
      arrested by density, E-cadherin colocalized and coimmunoprecipitated with alpha-
      and beta-catenins in the boundary region between adjacent cells. By contrast,
      immunocytostaining and Western blot analyses revealed that E-cadherin colocalized
      and coprecipitated with beta-catenin but not with alpha-catenin in exponentially
      growing cells at low density. As a comparable amount of alpha-catenin was
      detected in the total cell lysate of cells at different densities, it is
      suggested that alpha-catenin is present but dissociates from the E-cadherin-beta
      catenin complex in growing cells. beta-Catenin was tyrosine phosphorylated in
      growing cells at low density but not in quiescent cells at confluence. Tyrosine
      phosphorylation of beta-catenin was concomitantly induced with association of
      beta-catenin with EGF receptor (EGFR) when quiescent cells at confluence were
      dissociated into single cells by tryptic digestion, being accompanied by
      dissociation of alpha-catenin from E-cadherin. Both tyrosine phosphorylation and
      association of beta-catenin with EGFR were inhibited by tyrphostin, a specific
      inhibitor of the EGFR tyrosine kinase, whereas dissociation of alpha-catenin from
      E-cadherin was not. The results suggest that tyrosine phosphorylation of beta
      catenin is achieved by EGFR upon tryptic digestion of cells and concurrent with
      but independent of dissociation of alpha-catenin from E-cadherin. beta-Catenin
      thus phosphorylated at tyrosine is suggested to play the role in preventing alpha
      catenin once dissociated from reassociating with E-cadherin until cells reach
      confluence.

PMID- 9233780
TI  - The FHIT gene is alternatively spliced in normal kidney and renal cell carcinoma.
AB  - FHIT (Fragile Histidine Triad), a putative tumor suppressor gene, was cloned from
      fetal brain and colon cDNA libraries. Portions of this gene are deleted in
      esophageal, colon, lung and breast tumors, but this gene has not been found
      altered in sporadic renal cell carcinomas. We report here an alternatively
      spliced form of this gene cloned from a kidney cDNA library. This cDNA is 1189 bp
      in length, and contains an additional 94 bp exon, designated exon 2a (E2a). This
      novel sequence is located between exon 2 and exon 3 of the FHIT gene's
      untranslated region and exon 2a is present in all normal kidney tissues and cell
      lines. Analyses performed on sporadic renal cell carcinoma (RCC) tissues and cell
      lines, show consistent loss of exon 8 of the FHIT cDNA in almost 60% of the
      cases. Interestingly, in a familial, as well as, in a metastatic RCC, derived
      from a patient with the sporadic form, exon 2a and exon 3 are also deleted.
      Northern analyses with the exon 2a of the familial and the metastatic RCC
      demonstrates concurrent loss of expression of a 4.4 kb transcript with the loss
      of the E2a sequence, suggesting that exon 2a of the FHIT gene may play an
      important role in the oncogenesis of renal cell carcinoma.

PMID- 9233781
TI  - In vivo evidence for binding of p53 to consensus binding sites in the p21 and
      GADD45 genes in response to ionizing radiation.
AB  - The tumor suppressor protein p53 has a transcriptional activation activity
      thought to mediate its biologic function including G1 arrest and perhaps
      apoptosis. To learn more about p53's transactivator function in vivo, we
      performed genomic footprinting experiments examining p53-DNA interactions in the
      regulatory regions of the p53-regulated genes p21, GADD45, and MDM2. Using
      ionizing radiation to induce DNA damage in human ML-1 myeloblastic leukemia
      cells, the promoter and intronic regions of these genes containing p53-consensus
      binding sites were examined for in vivo footprints. There was a uniform and
      sustained expression of p53 protein as well as a strong induction of p21, GADD45,
      and MDM2 mRNA following irradiation. At the two p53 consensus binding sites in
      the p21 promoter, reduced DNaseI cleavage was observed in irradiated cells
      beginning 1 to 2h after irradiation, being most pronounced after 2 h and
      diminishing after 8 h. A partial in vivo footprint was also observed in the third
      intron of the GADD45 gene beginning 2 h after irradiation. No in vivo footprints
      were seen at the two p53 binding sites in the MDM2 gene. Our study provides
      direct evidence that the DNA damage-induced activity of p53 is mediated by its
      consensus DNA binding sites in the p21 and GADD45 genes. We suggest that the
      transient nature and relative instability of p53-DNA interactions in vivo may
      make the p53 protein more accessible to a rapid turnover pathway which might be
      impaired under conditions when the protein is stably bound to DNA.

PMID- 9233782
TI  - FHIT gene alterations in esophageal cancer and ulcerative colitis (UC).
AB  - FHIT (fragile histidine triad gene), a candidate tumor suppressor gene, was
      recently identified and cloned at chromosome 3p14.2. Alterations of this gene
      have been reported in a number of primary human tumors, including colorectal,
      esophageal, gastric and lung carcinomas. However, some reports have found no
      abnormalities in this gene. We investigated a total of 63 primary esophageal
      tumors, nine esophageal cancer cell lines and 17 ulcerative colitis-associated
      neoplasms (UCANs) for alterations of FHIT. In 13 esophageal tumors, we employed
      overlapping reverse transcriptase-PCRs (RT-PCRs) to amplify and sequence the
      complete open reading frame of FHIT. One of 13 primary esophageal tumors analysed
      by RT-PCR expressed no detectable FHIT transcript; the remaining 12 expressed
      normal-sized transcripts with wild-type open reading frame sequences. In an
      additional 50 esophageal tumors, the polymorphic microsatellite loci D3S1300 and
      D3S1313 were used to evaluate loss of heterozygosity (LOH) at 3p14.2. Eleven of
      these 50 tumors showed LOH at one or both loci. In all these 11 tumors, genomic
      PCR and direct sequencing of FHIT exons 5-9 was performed. This analysis revealed
      that none of these 11 primary esophageal tumors contained any alterations in the
      FHIT open reading frame or adjacent intron sequences. Finally, among 17 UCANs,
      the in vitro synthesized protein (IVSP) assay detected no truncated protein
      products, nor were there any abnormalities in size or DNA sequence of FHIT RT-PCR
      products. However, in six of nine esophageal carcinoma cell lines, no FHIT RT-PCR
      product was detectable using either of the overlapping primer sets. Genomic PCR
      and direct sequencing of exons 5-9, also performed in these nine cell lines,
      revealed wild-type sequence in eight cell lines; however, one cell line contained
      no exon 5 PCR product. This cell line also lacked detectable FHIT transcript.
      These data suggest that the open reading frame of FHIT is not important in the
      development or progression of most primary esophageal carcinomas or UCANs,
      although lack of expression of the FHIT transcript may be common in esophageal
      cancer-derived cell lines. The possibility of an additional tumor suppressor gene
      at chromosome 3p14.2 remains to be evaluated.

PMID- 9233783
TI  - Inhibition of cyclin D expression in human breast carcinoma cells by retinoids in
      vitro.
AB  - Transfection and transgenic mouse experiments supported an oncogenic role for
      cyclin D1 in breast cancer. We recently reported that noninvasive carcinoma in
      situ lesions of the human breast overexpress cyclin D, suggesting that this
      molecular event may represent a valuable target for chemoprevention. The purpose
      of the present series of investigations was to identify agents which could reduce
      the cyclin D expression of breast cells. We report that 9-cis retinoic acid (9
      cis RA) and all trans retinoic acid (tRA) inhibited the cyclin D1 and D3
      expression levels of human MCF-7, ZR-75 and T-47D breast carcinoma cells in
      vitro. Where detectable, similar trends were observed in the immortalized, HBL
      100 and MCF-10A breast cell lines. Cyclin D2 was undetectable. The effect of
      retinoids was both dose- and time-dependent, and correlated with altered cell
      cycle kinetics and proliferative status. Retinoids were also found to inhibit the
      expression levels of other cell cycle related proteins, including Cdk2 and Cdk4,
      resulting in lower kinase activities. In contrast to other breast prevention
      studies, no synergistic effect was observed with retinoids and tamoxifen. The
      data indicate that retinoids can potently reduce cyclin D expression levels in a
      variety of breast cell lines in vitro, and suggest further consideration of this
      mechanism for the chemoprevention of breast cancer.

PMID- 9233784
TI  - Mutation analysis of the transforming growth factor-beta type II receptor in
      human cell lines resistant to growth inhibition by transforming growth factor
      beta.
AB  - The transforming growth factor-beta (TGF-beta) binds the type II TGF-beta growth
      factor receptor (RII) to inhibit the growth of most epithelial tissues. Most
      human colon and gastric cancers with microsatellite instability (MI) have
      frameshift mutations in polynucleotide repeats within the RII coding region;
      these mutations truncate the receptor protein and disable the serine/threonine
      kinase to produce TGF-beta resistance. To further investigate the type, frequency
      and tissue distribution of RII mutations, we selected 24 human cancer cell lines
      from various tissues which were previously reported to be resistant to the
      inhibitory effects of TGF-beta. We developed protocols for non-isotopic SSCP
      analysis of PCR products from genomic DNA samples, and we tested them for
      microsatellite instability. PCR-SSCP analysis followed by DNA sequencing
      identified deletion mutations in the exon 3 poly-adenine tract in three colon
      tumor cell lines: LS174T and SW48 had a single base deletion and LS411 had a two
      base deletion. Among the 24 previously unreported cell lines, only these three
      demonstrated microsatellite instability. These and other recent data indicate
      that RII mutations are essentially confined to colon and gastric cancers with
      microsatellite instability. The narrow spectrum of tissues containing RII
      mutations illustrates the complexity of genetic checkpoints in human
      carcinogenesis.

PMID- 9233785
TI  - The crystal structure of the signal recognition particle Alu RNA binding
      heterodimer, SRP9/14.
AB  - The mammalian signal recognition particle (SRP) is an 11S cytoplasmic
      ribonucleoprotein that plays an essential role in protein sorting. SRP recognizes
      the signal sequence of the nascent polypeptide chain emerging from the ribosome,
      and targets the ribosome-nascent chain-SRP complex to the rough endoplasmic
      reticulum. The SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68
      and SRP72) and a single 300 nucleotide RNA molecule. SRP9 and SRP14 proteins form
      a heterodimer that binds to the Alu domain of SRP RNA which is responsible for
      translation arrest. We report the first crystal structure of a mammalian SRP
      protein, that of the mouse SRP9/14 heterodimer, determined at 2.5 A resolution.
      SRP9 and SRP14 are found to be structurally homologous, containing the same alpha
      beta-beta-beta-alpha fold. This we designate the Alu binding module (Alu bm), an
      additional member of the family of small alpha/beta RNA binding domains. The
      heterodimer has pseudo 2-fold symmetry and is saddle like, comprising a strongly
      curved six-stranded amphipathic beta-sheet with the four helices packed on the
      convex side and the exposed concave surface being lined with positively charged
      residues.

PMID- 9233786
TI  - A single amino acid can switch the oligomerization state of the alpha-helical
      coiled-coil domain of cartilage matrix protein.
AB  - We have studied the oligomerization of an alpha-helical coiled-coil using as an
      example a peptide corresponding to the C-terminal domain of cartilage matrix
      protein. By replacing one arginine residue, which forms an interchain ionic
      interaction with a glutamic acid residue, with glutamine, we found that this
      peptide assembles into a homotetramer at neutral pH in contrast to the native
      molecule which forms homotrimers. At acidic and basic pH, however, we again
      observed the trimer conformation. Another arginine, which is probably involved in
      an intrachain salt bridge, has no effect on the assembly. Our data demonstrate
      that besides the specific distribution of hydrophobic residues, interchain ionic
      interactions can be crucial in modulating the association behavior of alpha
      helical coiled-coil domains.

PMID- 9233787
TI  - Crystal structure of a pair of follistatin-like and EF-hand calcium-binding
      domains in BM-40.
AB  - BM-40 (also known as SPARC or osteonectin) is an anti-adhesive secreted
      glycoprotein involved in tissue remodelling. Apart from an acidic N-terminal
      segment, BM-40 consists of a follistatin-like (FS) domain and an EF-hand calcium
      binding (EC) domain. Here we report the crystal structure at 3.1 A resolution of
      the FS-EC domain pair of human BM-40. The two distinct domains interact through a
      small interface that involves the EF-hand pair of the EC domain. Residues
      implicated in cell binding, inhibition of cell spreading and disassembly of focal
      adhesions cluster on one face of BM-40, opposite the binding epitope for
      collagens and the N-linked carbohydrate. The elongated FS domain is structurally
      related to serine protease inhibitors of the Kazal family. Notable differences
      are an insertion into the inhibitory loop in BM-40 and a protruding N-terminal
      beta-hairpin with striking similarities to epidermal growth factor. This hairpin
      is likely to act as a rigid spacer in proteins containing tandemly repeated FS
      domains, such as follistatin and agrin, and forms the heparin-binding site in
      follistatin.

PMID- 9233788
TI  - Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A
      resolution.
AB  - Ubiquitin C-terminal hydrolases catalyze the removal of adducts from the C
      terminus of ubiquitin. We have determined the crystal structure of the
      recombinant human Ubiquitin C-terminal Hydrolase (UCH-L3) by X-ray
      crystallography at 1.8 A resolution. The structure is comprised of a central
      antiparallel beta-sheet flanked on both sides by alpha-helices. The beta-sheet
      and one of the helices resemble the well-known papain-like cysteine proteases,
      with the greatest similarity to cathepsin B. This similarity includes the UCH-L3
      active site catalytic triad of Cys95, His169 and Asp184, and the oxyanion hole
      residue Gln89. Papain and UCH-L3 differ, however, in strand and helix
      connectivity, which in the UCH-L3 structure includes a disordered 20 residue loop
      (residues 147-166) that is positioned over the active site and may function in
      the definition of substrate specificity. Based upon analogy with inhibitor
      complexes of the papain-like enzymes, we propose a model describing the binding
      of ubiquitin to UCH-L3. The UCH-L3 active site cleft appears to be masked in the
      unliganded structure by two different segments of the enzyme (residues 9-12 and
      90-94), thus implying a conformational change upon substrate binding and
      suggesting a mechanism to limit non-specific hydrolysis.

PMID- 9233789
TI  - beta-catenin is a target for the ubiquitin-proteasome pathway.
AB  - beta-catenin is a central component of the cadherin cell adhesion complex and
      plays an essential role in the Wingless/Wnt signaling pathway. In the current
      model of this pathway, the amount of beta-catenin (or its invertebrate homolog
      Armadillo) is tightly regulated and its steady-state level outside the cadherin
      catenin complex is low in the absence of Wingless/Wnt signal. Here we show that
      the ubiquitin-dependent proteolysis system is involved in the regulation of beta
      catenin turnover. beta-catenin, but not E-cadherin, p120(cas) or alpha-catenin,
      becomes stabilized when proteasome-mediated proteolysis is inhibited and this
      leads to the accumulation of multi-ubiquitinated forms of beta-catenin.
      Mutagenesis experiments demonstrate that substitution of the serine residues in
      the glycogen synthase kinase 3beta (GSK3beta) phosphorylation consensus motif of
      beta-catenin inhibits ubiquitination and results in stabilization of the protein.
      This motif in beta-catenin resembles a motif in IkappaB (inhibitor of NFkappaB)
      which is required for the phosphorylation-dependent degradation of IkappaB via
      the ubiquitin-proteasome pathway. We show that ubiquitination of beta-catenin is
      greatly reduced in Wnt-expressing cells, providing the first evidence that the
      ubiquitin-proteasome degradation pathway may act downstream of GSK3beta in the
      regulation of beta-catenin.

PMID- 9233790
TI  - Caspase activity is required for commitment to Fas-mediated apoptosis.
AB  - Recognition of the widespread importance of apoptosis has been one of the most
      significant changes in the biomedical sciences in the past decade. The molecular
      processes controlling and executing cell death through apoptosis are, however,
      still poorly understood. The ICE (Interleukin-1beta Converting Enzyme) family
      recently named the caspases for cysteine aspartate-specific proteases-plays a
      central role in apoptosis and may well constitute part of the conserved core
      mechanism of the process. Potentially, these proteases may be of great
      significance, both in the pathology associated with failure of apoptosis and also
      as targets for therapeutic intervention where apoptosis occurs inappropriately,
      e.g. in degenerative disease and AIDS. However, this is only likely if caspase
      activity is required before commitment to mammalian cell death. Here, we have
      used both peptide inhibitors and crmA transfection to inhibit these proteases in
      intact cells. Our experiments show that selective inhibition of some caspases
      protects human T cells (Jurkat and CEM-C7) from Fas-induced apoptosis,
      dramatically increasing their survival (up to 320-fold) in a colony-forming
      assay. This suggests that dysfunction of some, but not all, caspases could indeed
      play a crucial part in the development of some cancers and autoimmune disease,
      and also that these proteases could be appropriate molecular targets for
      preventing apoptosis in degenerative disease.

PMID- 9233791
TI  - Specific arginine and threonine residues control anion binding and transport in
      the light-driven chloride pump halorhodopsin.
AB  - The light-driven chloride pump halorhodopsin (HR), a halobacterial retinal
      protein, was studied by comparing wild type with specific mutants. Changes of
      conserved arginine and threonine residues in the transmembrane regions could be
      classified in two categories: in the extracellular half of the molecule,
      mutations influence anion uptake and binding. R108 mutations abolish all anion
      effects previously attributed to two distinct binding sites and change the
      characteristic photochemistry. Neutral residues at position 108 completely
      inactivate the pump. T111 increases the affinity of this anion binding site
      without being essentially important. In the photochemical cycles of the mutants
      T111V and Q105E, a red-shifted absorbing intermediate is enriched indicating
      retarded anion uptake. On the cytoplasmic side, mutations do not change anion
      binding properties of the unphotolyzed protein, but slow down anion release
      thereby reducing the chloride transport activity and the photocycling rate. The
      lowest activity is found for T203V, while R200 mutations have weaker effects.
      Thus, in the symmetrically arranged pairs R108/T111 and T203/R200, threonine and
      arginine play different roles, reflecting high affinity anion uptake by the
      former and effective anion release catalyzed by the latter residues. A model for
      the anion transport mechanism in HR is suggested comprising the specific
      functions of channel-lining residues.

PMID- 9233792
TI  - Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria
      and behavioral abnormalities but no neurodegeneration.
AB  - Four L-glutamate neurotransmitter transporters, the three Na(+)-dependent GLAST
      1, GLT-1 and EAAC-1, and the Cl(-)-dependent EAAT-4, form a new family of
      structurally related integral plasma membrane proteins with different
      distribution in the central nervous system. They may have pivotal functions in
      the regulation of synaptic L-glutamate concentration during neurotransmission and
      are believed to prevent glutamate neurotoxicity. To investigate the specific
      physiological and pathophysiological role of the neuronal EAAC-1, which is also
      expressed in kidney and small intestine, we have generated two independent mouse
      lines lacking EAAC-1. eaac-1(-/-) mice develop dicarboxylic aminoaciduria. No
      neurodegeneration has been observed during a period of >12 months, but homozygous
      mutants display a significantly reduced spontaneous locomotor activity.

PMID- 9233793
TI  - Mitochondrial activation directly triggers the exocytosis of insulin in
      permeabilized pancreatic beta-cells.
AB  - In the pancreatic beta-cell, insulin secretion is stimulated by glucose
      metabolism resulting in membrane potential-dependent elevation of cytosolic Ca2+
      ([Ca2+]c). This cascade involves the mitochondrial membrane potential (delta
      psi[m]) hyperpolarization and elevation of mitochondrial Ca2+ ([Ca2+]m) which
      activates the Ca(2+)-sensitive NADH-generating dehydrogenases. Metabolism
      secretion coupling requires unidentified signals, other than [Ca2+]c, possibly
      generated by the mitochondria through the rise in [Ca2+]m. To test this paradigm,
      we have established an alpha-toxin permeabilized cell preparation permitting the
      simultaneous monitoring of [Ca2+] with mitochondrially targeted aequorin and
      insulin secretion under conditions of saturating [ATP] (10 mM) and of clamped
      [Ca2+]c at substimulatory levels (500 nM). The tricarboxylic acid (TCA) cycle
      intermediate succinate hyperpolarized delta psi(m), raised [Ca2+]m up to 1.5
      microM and stimulated insulin secretion 20-fold, without changing [Ca2+]c.
      Blockade of the uniporter-mediated Ca2+ influx into the mitochondria abolished
      the secretory response. Moreover, glycerophosphate, which raises [Ca2+]m by
      hyperpolarizing delta psi(m) without supplying carbons to the TCA cycle, failed
      to stimulate exocytosis. Activation of the TCA cycle with citrate evoked
      secretion only when combined with glycerophosphate. Thus, mitochondrially driven
      insulin secretion at permissive [Ca2+]c requires both a substrate for the TCA
      cycle and a rise in [Ca2+]m. Therefore, mitochondrial metabolism generates
      factors distinct from Ca2+ and ATP capable of inducing insulin exocytosis.

PMID- 9233795
TI  - Pathway specificity for a delta pH-dependent precursor thylakoid lumen protein is
      governed by a 'Sec-avoidance' motif in the transfer peptide and a 'Sec
      incompatible' mature protein.
AB  - Cleavable N-terminal targeting signals direct the translocation of lumenal
      proteins across the chloroplast thylakoid membrane by either a Sec-type or delta
      pH-driven protein translocase. The targeting signals specify choice of
      translocation pathway, yet all resemble typical bacterial 'signal' peptides in
      possessing a charged N-terminus (N-domain), hydrophobic core region (H-domain)
      and more polar C-terminal region (C-domain). We have previously shown that a twin
      arginine motif in the N-domain is essential for targeting by the delta pH
      dependent pathway, but it has remained unclear why targeting signals for this
      system (transfer peptides) are not recognized by the Sec apparatus. We show here
      that the conserved charge distribution around the H-domain in the 23K transfer
      peptide (twin-Arg in the N-domain, Lys in the C-domain) constitutes a 'Sec
      avoidance' signal. The C-domain Lys, while not important for delta pH-dependent
      targeting, is the only barrier to Sec-dependent translocation; its removal
      generates an apparently perfect signal peptide. Conversely, insertion of twin-Arg
      into the N-domain of a Sec substrate has little effect, as has insertion of a C
      domain Lys, but the combined substitutions almost totally block transport. We
      also show that the 23K mature protein is incapable of being targeted by the Sec
      pathway, and it is proposed that the role of the Sec-avoidance motif in the
      transfer peptide is to prevent futile interactions with the Sec apparatus.

PMID- 9233794
TI  - Antigen endocytosis and presentation mediated by human membrane IgG1 in the
      absence of the Ig(alpha)/Ig(beta) dimer.
AB  - Membrane immunoglobulin (mIg) M and D heavy chains possess minimal (KVK)
      cytoplasmic tails and associate with the Ig alpha/Ig beta (CD79) dimer to achieve
      surface expression and antigen presentation function. In contrast, the
      cytoplasmic tail of mIgG is extended by 25 residues (gamma ct). We have tested
      the possibility that mIgG can perform antigen capture and presentation functions
      independently of the Ig(alpha)/beta dimer. We show that CD4/(gamma)ct chimeras
      are efficiently endocytosed partially dependent on a tyrosine residue in
      (gamma)ct. In addition, human mIgG was expressed on the surface of
      Ig(alpha)/Ig(beta)-negative non-lymphoid cells and mediated antigen capture and
      endocytosis. Antigen-specific human mIgG targeted antigen to MIIC-type vesicles
      in the Ig(alpha)/beta negative melanoma Mel JuSo and augmented antigen
      presentation 1000-fold, identical to the augmentation seen in Ig(alpha)/beta
      positive B-cells expressing the same transfected mIgG. Thus, unlike mIgM, mIgG
      has autonomous antigen capture and presentation capacity, which may have evolved
      to reduce or eliminate the BCR's dependence on additional accessory molecules.

PMID- 9233796
TI  - Meiotic cell cycle in Xenopus oocytes is independent of cdk2 kinase.
AB  - In vertebrates, M phase-promoting factor (MPF), a universal G2/M regulator in
      eukaryotic cells, drives meiotic maturation of oocytes, while cytostatic factor
      (CSF) arrests mature oocytes at metaphase II until fertilization. Cdk2 kinase, a
      G1/S regulator in higher eukaryotic cells, is activated during meiotic maturation
      of Xenopus oocytes and, like Mos (an essential component of CSF), is proposed to
      be involved in metaphase II arrest in mature oocytes. In addition, cdk2 kinase
      has been shown recently to be essential for MPF activation in Xenopus embryonic
      mitosis. Here we report injection of Xenopus oocytes with the cdk2 kinase
      inhibitor p21Cip in order to (re)evaluate the role of cdk2 kinase in oocyte
      meiosis. Immature oocytes injected with p21Cip can enter both meiosis I and
      meiosis II normally, as evidenced by the typical fluctuations in MPF activity.
      Moreover, mature oocytes injected with p21Cip are retained normally in metaphase
      II for a prolonged period, whereas those injected with neutralizing anti-Mos
      antibody are released readily from metaphase II arrest. These results argue
      strongly against a role for cdk2 kinase in MPF activation and its proposed role
      in metaphase II arrest, in Xenopus oocyte meiosis. We discuss the possibility
      that cdk2 kinase stored in oocytes may function, as a maternal protein, solely
      for early embryonic cell cycles.

PMID- 9233797
TI  - Mechanism of TGFbeta receptor inhibition by FKBP12.
AB  - Transforming growth factor-beta (TGFbeta) signaling requires phosphorylation of
      the type I receptor TbetaR-I by TbetaR-II. Although TGFbeta promotes the
      association of TbetaR-I with TbetaR-II, these receptor components have affinity
      for each other which can lead to their ligand-independent activation. The
      immunophilin FKBP12 binds to TbetaR-I and inhibits its signaling function. We
      investigated the mechanism and functional significance of this effect. FKBP12
      binding to TbetaR-I involves the rapamycin/Leu-Pro binding pocket of FKBP12 and a
      Leu-Pro sequence located next to the activating phosphorylation sites in TbetaR
      I. Mutations in the binding sites of FKBP12 or TbetaR-I abolish the interaction
      between these proteins, leading to receptor activation in the absence of added
      ligand. FKBP12 does not inhibit TbetaR-I association with TbetaR-II, but inhibits
      TbetaR-I phosphorylation by TbetaR-II. Rapamycin, which blocks FKBP12 binding to
      TbetaR-I, reverses the inhibitory effect of FKBP12 on TbetaR-I phosphorylation.
      By impeding the activation of TGFbeta receptor complexes formed in the absence of
      ligand, FKBP12 may provide a safeguard against leaky signaling resulting from the
      innate tendency of TbetaR-I and TbetaR-II to interact with each other.

PMID- 9233798
TI  - Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to
      specific SH2 domain proteins in neuronal cells.
AB  - Eph-related receptor tyrosine kinases have been implicated in the control of
      axonal navigation and fasciculation. To investigate the biochemical mechanisms
      underlying such functions, we have expressed the EphB2 receptor (formerly
      Nuk/Cek5/Sek3) in neuronal NG108-15 cells, and have observed the tyrosine
      phosphorylation of multiple cellular proteins upon activation of EphB2 by its
      ligand, ephrin-B1 (formerly Elk-L/Lerk2). The activated EphB2 receptor induced
      the tyrosine phosphorylation of a 62-64 kDa protein (p62[dok]), which in turn
      formed a complex with the Ras GTPase-activating protein (RasGAP) and SH2/SH3
      domain adaptor protein Nck. RasGAP also bound through its SH2 domains to tyrosine
      phosphorylated EphB2 in vitro, and complexed with activated EphB2 in vivo. We
      have localized an in vitro RasGAP-binding site to conserved tyrosine residues
      Y604 and Y610 in the juxtamembrane region of EphB2, and demonstrated that
      substitution of these amino acids abolishes ephrin-B1-induced signalling events
      in EphB2-expressing NG108-15 cells. These tyrosine residues are followed by
      proline at the + 3 position, consistent with the binding specificity of RasGAP
      SH2 domains determined using a degenerate phosphopeptide library. These results
      identify an EphB2-activated signalling cascade involving proteins that
      potentially play a role in axonal guidance and control of cytoskeletal
      architecture.

PMID- 9233799
TI  - The N-terminal globular domain of Eph receptors is sufficient for ligand binding
      and receptor signaling.
AB  - The Eph family of receptor protein-tyrosine kinases (RTKs) have recently been
      implicated in patterning and wiring events in the developing nervous system. Eph
      receptors are unique among other RTKs in that they fall into two large subclasses
      that show distinct ligand specificities and for the fact that they themselves
      might function as 'ligands', thereby activating bidirectional signaling. To gain
      insight into the mechanisms of ligand-receptor interaction, we have mapped the
      ligand binding domain in Eph receptors. By using a series of deletion and domain
      substitution mutants, we now report that an N-terminal globular domain of the
      Nuk/Cek5 receptor is the ligand binding domain of the transmembrane ligand Lerk2.
      Using focus formation assays, we show that the Cek5 globular domain is sufficient
      to confer Lerk2-dependent transforming activity on the Cek9 orphan receptor.
      Extending our binding studies to other members of both subclasses of receptors,
      it became apparent that the same domain is used for binding of both transmembrane
      and glycosylphosphatidyl-anchored ligands. Our studies have determined the first
      structural elements involved in ligand-receptor interaction and will allow more
      fine-tuned genetic experiments to elucidate the mechanism of action of these
      important guidance molecules.

PMID- 9233800
TI  - Proteolytic processing regulates receptor specificity and activity of VEGF-C.
AB  - The recently identified vascular endothelial growth factor C (VEGF-C) belongs to
      the platelet-derived growth factor (PDGF)/VEGF family of growth factors and is a
      ligand for the endothelial-specific receptor tyrosine kinases VEGFR-3 and VEGFR
      2. The VEGF homology domain spans only about one-third of the cysteine-rich VEGF
      C precursor. Here we have analysed the role of post-translational processing in
      VEGF-C secretion and function, as well as the structure of the mature VEGF-C. The
      stepwise proteolytic processing of VEGF-C generated several VEGF-C forms with
      increased activity towards VEGFR-3, but only the fully processed VEGF-C could
      activate VEGFR-2. Recombinant 'mature' VEGF-C made in yeast bound VEGFR-3 (K[D] =
      135 pM) and VEGFR-2 (K[D] = 410 pM) and activated these receptors. Like VEGF,
      mature VEGF-C increased vascular permeability, as well as the migration and
      proliferation of endothelial cells. Unlike other members of the PDGF/VEGF family,
      mature VEGF-C formed mostly non-covalent homodimers. These data implicate
      proteolytic processing as a regulator of VEGF-C activity, and reveal novel
      structure-function relationships in the PDGF/VEGF family.

PMID- 9233801
TI  - A kinase subdomain of transforming growth factor-beta (TGF-beta) type I receptor
      determines the TGF-beta intracellular signaling specificity.
AB  - Transforming growth factor-beta (TGF-beta) signals through a heteromeric complex
      of related type I and type II serine/threonine kinase receptors. In Mv1Lu cells
      the type I receptor TbetaRI mediates TGF-beta-induced gene expression and growth
      inhibition, while the closely related type I receptors Tsk7L and TSR1 are
      inactive in these responses. Using chimeras between TbetaRI and Tsk7L or TSR1, we
      have defined the structural requirements for TGF-beta signaling by TbetaRI. The
      extracellular/transmembrane or cytoplasmic domains of TbetaRI and Tsk7L were
      functionally not equivalent. The juxtamembrane domain, including the GS motif,
      and most regions in the kinase domain can functionally substitute for each other,
      but the alphaC-beta4-beta5 region from kinase subdomains III to V conferred a
      distinct signaling ability. Replacement of this sequence in TbetaRI by the
      corresponding domain of Tsk7L inactivated TGF-beta signaling, whereas its
      introduction into Tsk7L conferred TGF-beta signaling. The differential signaling
      associated with this region was narrowed down to a sequence of eight amino acids,
      the L45 loop, which is exposed in the three-dimensional kinase structure and
      diverges highly between TbetaRI and Tsk7L or TSR1. Replacement of the L45
      sequence in Tsk7L with that of TbetaRI conferred TGF-beta responsiveness to the
      Tsk7L cytoplasmic domain in Mv1Lu cells. Thus, the L45 sequence between kinase
      subdomains IV and V specifies TGF-beta responsiveness of the type I receptor.

PMID- 9233802
TI  - c-Myb and Ets proteins synergize to overcome transcriptional repression by ZEB.
AB  - The Zfh family of zinc finger/homeodomain proteins was first identified in
      Drosophila where it is required for differentiation of tissues such as the
      central nervous system and muscle. ZEB, a vertebrate homolog of Zfh-1, binds a
      subset of E boxes and blocks myogenesis through transcriptional repression of
      muscle genes. We present evidence here that ZEB also has an important role in
      controlling hematopoietic gene transcription. Two families of transcription
      factors that are required for normal hematopoiesis are c-Myb and Ets. These
      factors act synergistically to activate transcription, and this synergy is
      required for transcription of at least several important hematopoietic genes. ZEB
      blocks the activity of c-Myb and Ets individually, but together the factors
      synergize to resist this repression. Such repression imposes a requirement for
      both c-Myb and Ets for transcriptional activity, providing one explanation for
      why synergy between these factors is important. The balance between repression by
      ZEB and transcriptional activation by c-Myb/Ets provides a flexible regulatory
      mechanism for controlling gene expression in hematopoietic cells. We demonstrate
      that one target of this positive/negative regulation in vivo is the alpha4
      integrin, which play a key role in normal hematopoiesis and function of mature
      leukocytes.

PMID- 9233803
TI  - ZEB, a vertebrate homolog of Drosophila Zfh-1, is a negative regulator of muscle
      differentiation.
AB  - A number of genes, spanning the evolutionary scale from yeast to mammals, that
      are involved in spatial and temporal patterning during development contain zinc
      finger and homeodomain motifs. One such zinc finger/homeodomain protein is
      Drosophila Zfh-1, a member of the zfh family of Drosophila genes, which is
      expressed in muscle precursors and is critical for the proper development of
      muscle. Here we demonstrate that a vertebrate homolog of Zfh-1 (ZEB) is a
      negative regulator of muscle differentiation. We show that ZEB binds to a subset
      of E boxes in muscle genes and functions by actively repressing transcription.
      One target of this repression is the members of the MEF-2 family, which synergize
      with proteins of the myogenic basic helix-loop-helix family (bHLH) (myoD, myf-5,
      myogenin and MRF-4) to induce myogenic differentiation. As muscle differentiation
      proceeds, myogenic bHLH proteins accumulate to levels sufficient to displace ZEB
      from the E boxes, releasing the repression and allowing bHLH proteins to further
      activate transcription. This mechanism of active transcriptional repression
      distinguishes ZEB from other negative regulators of myogenesis (Id, Twist and I
      mfa) that inhibit muscle differentiation by simply binding and inactivating
      myogenic factors. The relative affinity of ZEB versus myogenic bHLH proteins
      varies for E boxes in different genes such that ZEB would be displaced from
      different genes at distinct times as myogenic bHLH proteins accumulate during
      myogenesis, thus providing a mechanism to regulate temporal order of gene
      expression.

PMID- 9233804
TI  - A new gene encoding a putative transcription factor regulated by the Drosophila
      circadian clock.
AB  - Circadian rhythms of locomotor activity and eclosion in Drosophila depend upon
      the reciprocal autoregulation of the period (per) and timeless (tim) genes. As
      part of this regulatory loop, per and tim mRNA levels oscillate in a circadian
      fashion. Other cycling transcripts may participate in this central pacemaker
      mechanism or represent outputs of the clock. In this paper, we report the
      isolation of Crg-1, a new circadianly regulated gene. Like per and tim transcript
      levels, Crg-1 transcript levels oscillate with a 24 h period in light:dark (LD)
      conditions, with a maximal abundance at the beginning of the night. These
      oscillations persist in complete darkness and depend upon per and tim proteins.
      The putative CRG-1 proteins show some sequence similarity with the DNA-binding
      domain of the HNF3/fork head family of transcription factors. In the adult head,
      in situ hybridization analysis reveals that per and Crg-1 have similar expression
      patterns in the eyes and optic lobes.

PMID- 9233805
TI  - Axial (HNF3beta) and retinoic acid receptors are regulators of the zebrafish
      sonic hedgehog promoter.
AB  - The signalling molecule Sonic hedgehog is involved in a multitude of distinct
      patterning processes during vertebrate embryogenesis. In the nascent body axis of
      the zebrafish embryo, sonic hedgehog is co-expressed with axial (HNF3beta in
      mammals), a transcription regulator of the winged helix family. We show here that
      misexpression of axial leads to ectopic activation of sonic hedgehog expression
      in the zebrafish, suggesting that axial is a regulator of sonic hedgehog
      transcription. The sonic hedgehog gene was cloned from zebrafish and its promoter
      was characterized with respect to activation by axial. Expression of axial or rat
      HNF3beta in HeLa cells results in activation of co-transfected sonic hedgehog
      promoter-CAT fusion genes. This effect is mediated by two Axial (HNF3beta)
      recognition sequences. We furthermore identified a retinoic acid response element
      (RARE) in the sonic hedgehog upstream region which can be bound by retinoic acid
      receptor (RAR) and retinoid X receptor (RXR) heterodimers in vitro and confers
      retinoic acid inducibility to the sonic hedgehog promoter in the HeLa cell
      system. Our results suggest that both Axial (HNF3beta) and retinoic acid
      receptors are direct regulators of the sonic hedgehog gene.

PMID- 9233806
TI  - A lineage-selective knockout establishes the critical role of transcription
      factor GATA-1 in megakaryocyte growth and platelet development.
AB  - Transcription factor GATA-1 is essential for red blood cell maturation and,
      therefore, for survival of developing mouse embryos. GATA-1 is also expressed in
      megakaryocytes, mast cells, eosinophils, multipotential hematopoietic progenitors
      and Sertoli cells of the testis, where its functions have been elusive. Indeed,
      interpretation of gene function in conventional knockout mice is often limited by
      embryonic lethality or absence of mature cells of interest, creating the need for
      alternate methods to assess gene function in selected cell lineages. Emerging
      strategies for conditional gene inactivation through site-specific recombinases
      rely on the availability of mouse strains with high fidelity of transgene
      expression and efficient, tissue-restricted DNA excision. In an alternate
      approach, we modified sequences upstream of the GATA-1 locus in embryonic stem
      cells, including a DNase I-hypersensitive region. This resulted in generation of
      mice with selective loss of megakaryocyte GATA-1 expression, yet sufficient
      erythroid cell levels to avoid lethal anemia. The mutant mice have markedly
      reduced platelet numbers, associated with deregulated megakaryocyte proliferation
      and severely impaired cytoplasmic maturation. These findings reveal a critical
      role for GATA-1 in megakaryocyte growth regulation and platelet biogenesis, and
      illustrate how targeted mutation of cis-elements can generate lineage-specific
      knockout mice.

PMID- 9233807
TI  - Subtle hydrophobic interactions between the seventh residue of the zinc finger
      loop and the first base of an HGATAR sequence determine promoter-specific
      recognition by the Aspergillus nidulans GATA factor AreA.
AB  - A change of a universally conserved leucine to valine in the DNA-binding domain
      of the GATA factor AreA results in inability to activate some AreA-dependent
      promoters, including that of the uapA gene encoding a specific urate-xanthine
      permease. Some other AreA-dependent promoters become able to function more
      efficiently than in the wild-type context. A methionine in the same position
      results in a less extreme, but opposite effect. Suppressors of the AreA(Val)
      mutation mapping in the uapA promoter show that the nature of the base in the
      first position of an HGATAR (where H stands for A, T or C) sequence determines
      the relative affinity of the promoter for the wild-type and mutant forms of AreA.
      In vitro binding studies of wild-type and mutant AreA proteins are completely
      consistent with the phenotypes in vivo. Molecular models of the wild-type and
      mutant AreA-DNA complexes derived from the atomic coordinates of the GATA-1
      AGATAA complex account both for the phenotypes observed in vivo and the binding
      differences observed in vitro. Our work extends the consensus of physiologically
      relevant binding sites from WGATAR to HGATAR, and provides a rationale for the
      almost universal evolutionary conservation of leucine at the seventh position of
      the Zn finger of GATA factors. This work shows inter alia that the sequence
      CGATAGagAGATAA, comprising two almost adjacent AreA-binding sites, is sufficient
      to ensure activation of transcription of the uapA gene.

PMID- 9233808
TI  - Cells strongly expressing Ig(kappa) transgenes show clonal recruitment of
      hypermutation: a role for both MAR and the enhancers.
AB  - The V regions of immunoglobulin kappa transgenes are targets for hypermutation in
      germinal centre B cells. We show by use of modified transgenes that the
      recruitment of hypermutation is substantially impaired by deletion of the nuclear
      matrix attachment region (MAR) which flanks the intron-enhancer (Ei). Decreased
      mutation is also obtained if Ei, the core region of the kappa3'-enhancer (E3') or
      the E3'-flank are removed individually. A broad correlation between expression
      and mutation is indicated not only by the fact that the deletions affecting
      mutation also give reduced transgene expression, but especially by the finding
      that, within a single mouse, transgene mutation was considerably reduced in
      germinal centre B cells that poorly expressed the transgene as compared with
      strongly expressing cells. We also observed that the diminished mutation in
      transgenes carrying regulatory element deletions was manifested by an increased
      proportion of B cells in which the transgene had not been targeted at all for
      mutation rather than in the extent of mutation accumulation once targeted. Since
      mutations appear to be incorporated stepwise, the results point to a connection
      between transcription initiation and the clonal recruitment of hypermutation,
      with hypermutation being more fastidious than transcription in requiring the
      presence of a full complement of regulatory elements.

PMID- 9233809
TI  - Transcriptional regulation in endoderm development: characterization of an
      enhancer controlling Hnf3g expression by transgenesis and targeted mutagenesis.
AB  - The hepatic nuclear factor 3gamma (Hnf3g) is a member of the winged helix gene
      family of transcription factors and is thought to be involved in anterior
      posterior regionalization of the primitive gut. In this study, cis-regulatory
      elements essential for the expression of Hnf3g in vivo have been characterized.
      To this end, a 170 kb yeast artificial chromosome (YAC) carrying the entire Hnf3g
      locus was isolated and modified with a lacZ reporter gene. The two mouse lines
      carrying the unfragmented Hnf3g-lacZ YAC showed tissue-specific, copy number
      dependent and position-independent expression, proving that 170 kb of the Hnf3g
      locus contain all elements important in the regulation of Hnf3g. Cis-regulatory
      elements necessary for expression of Hnf3g were identified in a three-step
      procedure. First, DNase I hypersensitive site mapping was used to delineate
      important chromatin regions around the gene required for tissue-specific
      activation of Hnf3g. Second, plasmid-derived transgenes and gene targeting of the
      endogenous Hnf3g gene locus were used to demonstrate that the 3'-flanking region
      of the gene is necessary and sufficient to direct reporter gene expression in
      liver, pancreas, stomach and small intestine. Third, a binding site for HNF
      1alpha and beta, factors expressed in organs derived from the endoderm such as
      liver, gut and pancreas, was identified in this 3'-enhancer and shown to be
      crucial for enhancer function in vitro. Based on its expression pattern we
      inferred that HNF-1beta is a likely candidate for directly activating Hnf3g gene
      expression during development.

PMID- 9233810
TI  - T-cell subset-specific expression of the IL-4 gene is regulated by a silencer
      element and STAT6.
AB  - During development of CD4+ T lymphocytes in the periphery, differential
      expression of cytokine genes, such as those of interleukin (IL)-2 and IL-4,
      occurs in distinct T-cell subsets. IL-4 is a cytokine produced by T-helper 2
      (Th2) cells, and the IL-4 receptor (IL-4R)-mediated signaling pathway is thought
      to be required for commitment to the Th2 phenotype. However, the molecular basis
      for development of the Th subset-specific production of IL-4 remains unclear. We
      demonstrate here that the IL-4 promoter is functional in Th1 and B cells which do
      not normally form IL-4 transcripts as well as in IL-4-producing T cells. Based on
      studies of the effect of several different upstream and downstream regions of the
      IL-4 gene on IL-4 promoter activity, a Th1-specific IL-4 silencer element was
      identified in the 3'-untranslated region. The silencer region contained a
      consensus sequence for a transcriptional factor that is normally regulated by the
      IL-4 R signaling pathway, STAT6. Nuclear expression of STAT6 protein, which was
      shown to bind to the silencer region, was observed in Th2 cells but not in Th1
      cells. Deletion of the STAT6-binding site from the silencer region and inhibition
      of STAT6 function resulted in the appearance of silencing function even in Th2
      cells. These results provide evidence that the silencer element, and the binding
      of STAT6 to this element, play a permissive role in determining the commitment
      into Th2 phenotype.

PMID- 9233811
TI  - Cell differentiation by interaction of two HMG-box proteins: Mat1-Mc activates M
      cell-specific genes in S.pombe by recruiting the ubiquitous transcription factor
      Ste11 to weak binding sites.
AB  - The Schizosaccharomyces pombe mfm1 gene is expressed in an M cell-specific
      fashion. This regulation requires two HMG-box proteins: the ubiquitous Ste11
      transcription factor and the M cell-controlling protein Mat1-Mc. Here we report
      that the mfm1 promoter contains a single, weak Stell-binding site (a so-called TR
      box) that can confer M-specificity on a heterologous promoter when present in
      eight copies. In vitro, both Mat1-Mc and Ste11 can bind this box with
      approximately the same affinity. The Mat1-Mc protein caused a dramatic increase
      in the DNA-binding of Ste11 to this box, under conditions where we could not
      detect Mat1-Mc in the resulting protein-DNA complex. When we changed a single
      base in the mfm1 TR-box, such that it resembled those boxes found in ubiquitously
      expressed genes, Ste11 binding was enhanced, and in vivo the mfm1 gene also
      became expressed in P cells where Mat1-Mc is absent. These findings suggest that
      M-specificity results from Mat1-Mc-mediated Ste11 binding to weak TR-boxes. We
      have also defined a novel motif (termed M-box), adjacent to the mfm1 TR-box, to
      which Mat1-Mc binds strongly. A DNA fragment containing both the TR- and the M
      box allowed the formation of a complex containing both Ste11 and Mat1-Mc. A
      single copy of this fragment was sufficient to activate a heterologous promoter
      in an M-specific fashion, suggesting that these two boxes act in a synergistic
      manner.

PMID- 9233812
TI  - Region 2.5 of the Escherichia coli RNA polymerase sigma70 subunit is responsible
      for the recognition of the 'extended-10' motif at promoters.
AB  - At some bacterial promoters, a 5'-TG-3' sequence element, located one base
      upstream of the -10 hexamer element, provides an essential motif necessary for
      transcription initiation. We have identified a mutant of the Escherichia coli RNA
      polymerase sigma70 subunit that has an altered preference for base sequences in
      this 'extended -10' region. We show that this mutant sigma70 subunit
      substantially increases transcription from promoters bearing 5'-TC-3' or 5'-TT-3'
      instead of a 5'-TG-3' motif, located one base upstream of the -10 hexamer. The
      mutant results from a single base pair substitution in the rpoD gene that causes
      a Glu to Gly change at position 458 of sigma70. This substitution identifies a
      functional region in sigma70 that is immediately adjacent to the well
      characterized region 2.4 (positions 434-453, previously shown to contact the -10
      hexamer). From these results, we conclude that this region (which we name region
      2.5) is involved in contacting the 5'-TG-3' motif found at some bacterial
      promoters: thus, extended -10 regions are recognized by an extended region 2 of
      the RNA polymerase sigma70 subunit.

PMID- 9233813
TI  - The two RNA polymerases encoded by the nuclear and the plastid compartments
      transcribe distinct groups of genes in tobacco plastids.
AB  - The plastid genome in photosynthetic higher plants encodes subunits of an
      Escherichia coli-like RNA polymerase (PEP) which initiates transcription from
      E.coli sigma70-type promoters. We have previously established the existence of a
      second nuclear-encoded plastid RNA polymerase (NEP) in photosynthetic higher
      plants. We report here that many plastid genes and operons have at least one
      promoter each for PEP and NEP (Class II transcription unit). However, a subset of
      plastid genes, including photosystem I and II genes, are transcribed from PEP
      promoters only (Class I genes), while in some instances (e.g. accD) genes are
      transcribed exclusively by NEP (Class III genes). Sequence alignment identified a
      10 nucleotide NEP promoter consensus around the transcription initiation site.
      Distinct NEP and PEP promoters reported here provide a general mechanism for
      group-specific gene expression through recognition by the two RNA polymerases.

PMID- 9233814
TI  - Formation of plant RNA virus replication complexes on membranes: role of an
      endoplasmic reticulum-targeted viral protein.
AB  - The mechanisms that direct positive-stranded RNA virus replication complexes to
      plant and animal cellular membranes are poorly understood. We describe a specific
      interaction between a replication protein of an RNA plant virus and membranes in
      vitro and in live cells. The tobacco etch virus (TEV) 6 kDa protein associated
      with membranes as an integral protein via a central 19 amino acid hydrophobic
      domain. In the presence or absence of other viral proteins, fluorescent fusion
      proteins containing the 6 kDa protein associated with large vesicular
      compartments derived from the endoplasmic reticulum (ER). Infection by TEV was
      associated with a collapse of the ER network into a series of discrete aggregated
      structures. Viral RNA replication complexes from infected cells were also
      associated with ER-like membranes. Targeting of TEV RNA replication complexes to
      membranous sites of replication is proposed to involve post-translational
      interactions between the 6 kDa protein and the ER.

PMID- 9233815
TI  - The plant defense response to cucumber mosaic virus in cowpea is elicited by the
      viral polymerase gene and affects virus accumulation in single cells.
AB  - Resistance to infection in cowpea by strains of cucumber mosaic virus (CMV)
      involves a local, hypersensitive response (HR) and a localization of infection.
      These responses can be separated by mutation at two sites (nucleotides 1978 and
      2007, in codons 631 and 641) in the CMV 2a polymerase gene. Changes to both sites
      of a restricted strain allow systemic infection without an HR and increase the
      accumulation of both the 2a protein and viral RNA in protoplasts, while changing
      position 1978 alone results in a systemic infection, a systemic HR, and an
      increase in viral RNA accumulation in protoplasts. It is suggested that the
      inhibition response observed in protoplasts, where an HR does not occur, leads to
      localization of infection in whole plants and that different plant genes are
      involved in eliciting the HR and the localization response.

PMID- 9233816
TI  - Purification of a functional enzymatic editing complex from Trypanosoma brucei
      mitochondria.
AB  - Kinetoplastid mitochondrial RNA editing, the insertion and deletion of U
      residues, is catalyzed by sequential cleavage, U addition or removal, and
      ligation reactions and is directed by complementary guide RNAs. We have purified
      a approximately 20S enzymatic complex from Trypanosoma brucei mitochondria that
      catalyzes a complete editing reaction in vitro. This complex possesses all four
      activities predicted to catalyze RNA editing: gRNA-directed endonuclease,
      terminal uridylyl transferase, 3' U-specific exonuclease, and RNA ligase.
      However, it does not contain other putative editing complex components: gRNA
      independent endonuclease, RNA helicase, endogenous gRNAs or pre-mRNAs, or a 25
      kDa gRNA-binding protein. The complex is composed of eight major polypeptides,
      three of which represent RNA ligase. These findings identify polypeptides
      representing catalytic editing factors, reveal the nature of this approximately
      20S editing complex, and suggest a new model of editosome assembly.

PMID- 9233817
TI  - Identification and characterization of a yeast homolog of U1 snRNP-specific
      protein C.
AB  - U1C is one of the three human U1 small nuclear ribonucleoprotein (snRNP)-specific
      proteins and is important for efficient complex formation between U1 snRNP and
      the pre-mRNA 5' splice site. We identified a hypothetical open reading frame in
      Saccharomyces cerevisiae as the yeast homolog of the human U1C protein. The gene
      is essential, and its product, YU1C, is associated with U1 snRNP. YU1C depletion
      gives rise to normal levels of U1 snRNP and does not have any detectable effect
      on U1 snRNP assembly. YU1C depletion and YU1C ts mutants affect pre-mRNA splicing
      in vivo, and extracts from these strains form low levels of commitment complexes
      and spliceosomes in vitro. These experiments indicate a role for YU1C in snRNP
      function. Structure probing with RNases shows that only the U1 snRNA 5' arm is
      hypersensitive to RNase I digestion when YU1C is depleted. Similar results were
      obtained with YU1C ts mutants, indicating that U1C contributes to a proper 5' arm
      structure prior to its base pairing interaction with the pre-mRNA 5' splice site.

PMID- 9233819
TI  - A viral sequence in the 3'-untranslated region mimics a 5' cap in facilitating
      translation of uncapped mRNA.
AB  - For recognition by the translational machinery, most eukaryotic cellular mRNAs
      have a 5' cap structure [e.g. m7G(5')ppp(5')N]. We describe a translation
      enhancer sequence (3'TE) located in the 3'-untranslated region (UTR) of the
      genome of the PAV barley yellow dwarf virus (BYDV-PAV) which stimulates
      translation from uncapped mRNA by 30- to 100-fold in vitro and in vivo to a level
      equal to that of efficient capped mRNAs. A four base duplication within the 3'TE
      destroyed the stimulatory activity. Efficient translation was recovered by
      addition of a 5' cap to this mRNA. Translation of both uncapped mRNA containing
      the 3'TE in cis and capped mRNA lacking any BYDV-PAV sequence was inhibited
      specifically by added 3'TE RNA in trans. This inhibition was reversed by adding
      initiation factor 4F (eIF4F), suggesting that the 3'TE, like the 5' cap, mediates
      eIF4F-dependent translation initiation. The BYDV-PAV 5'UTR was necessary for the
      3'TE to function, except when the 3'TE itself was moved to the 5'UTR. Thus, the
      3'TE is sufficient for recruiting the translation factors and ribosomes, while
      the viral 5'UTR may serve only for the long distance 3'-5' communication. Models
      are proposed to explain this novel mechanism of cap-independent translation
      initiation facilitated by the 3'UTR.

PMID- 9233818
TI  - An evolutionarily conserved U5 snRNP-specific protein is a GTP-binding factor
      closely related to the ribosomal translocase EF-2.
AB  - The driving forces behind the many RNA conformational changes occurring in the
      spliceosome are not well understood. Here we characterize an evolutionarily
      conserved human U5 small nuclear ribonucleoprotein (snRNP) protein (U5-116kD)
      that is strikingly homologous to the ribosomal elongation factor EF-2 (ribosomal
      translocase). A 114 kDa protein (Snu114p) homologous to U5-116kD was identified
      in Saccharomyces cerevisiae and was shown to be essential for yeast cell
      viability. Genetic depletion of Snu114p results in accumulation of unspliced pre
      mRNA, indicating that Snu114p is essential for splicing in vivo. Antibodies
      specific for U5-116kD inhibit pre-mRNA splicing in a HeLa nuclear extract in
      vitro. In HeLa cells, U5-116kD is located in the nucleus and colocalizes with
      snRNP-containing subnuclear structures referred to as speckles. The G domain of
      U5-116kD/Snu114p contains the consensus sequence elements G1-G5 important for
      binding and hydrolyzing GTP. Consistent with this, U5-116kD can be cross-linked
      specifically to GTP by UV irradiation of U5 snRNPs. Moreover, a single amino acid
      substitution in the G1 sequence motif of Snu114p, expected to abolish GTP-binding
      activity, is lethal, suggesting that GTP binding and probably GTP hydrolysis is
      important for the function of U5-116kD/Snu114p. This is to date the first
      evidence that a G domain-containing protein plays an essential role in the pre
      mRNA splicing process.

PMID- 9233820
TI  - Participation of the human p53 3'UTR in translational repression and activation
      following gamma-irradiation.
AB  - p53 protein levels have been shown to increase in a number of cells after
      treatment with genotoxic agents through a post-transcriptional mechanism. In
      gamma-irradiated human cells, the accumulation of p53 protein is accompanied by
      an increase in the association of p53 mRNA with large polysomes without any
      change in the level of p53 mRNA. This redistribution of p53 mRNA on polysomes in
      response to irradiation is consistent with enhanced translational activity of p53
      mRNA. We demonstrate that a region of the p53 3'-untranslated region (3'UTR)
      inhibits translation of a chimeric reporter mRNA in vivo. Induced elevation of
      reporter activity after gamma-irradiation was seen in cells expressing chimeric
      reporter-p53 3'UTR transcripts. These data taken together demonstrate
      translational control of p53 gene expression after gamma-irradiation and denote a
      previously unsuspected and novel role for the p53 3'UTR in controlling
      translation.

PMID- 9233821
TI  - Release factor RF3 in E.coli accelerates the dissociation of release factors RF1
      and RF2 from the ribosome in a GTP-dependent manner.
AB  - Ribosomes complexed with synthetic mRNA and peptidyl-tRNA, ready for peptide
      release, were purified by gel filtration and used to study the function of
      release factor RF3 and guanine nucleotides in the termination of protein
      synthesis. The peptide-releasing activity of RF1 and RF2 in limiting
      concentrations was stimulated by the addition of RF3 and GTP, stimulated, though
      to a lesser extent, by RF3 and a non-hydrolysable GTP analogue, and inhibited by
      RF3 and GDP or RF3 without guanine nucleotide. With short incubation times
      allowing only a single catalytic cycle of RF1 or RF2, peptide release activity
      was independent of RF3 and guanine nucleotide. RF3 hydrolysis of GTP to GDP +
      P(i) was dependent only on ribosomes and not on RF1 or RF2. RF3 affected neither
      the rate of association of RF1 and RF2 with the ribosome nor the catalytic rate
      of peptide release. A model is proposed which explains how RF3 recycles RF1 and
      RF2 by displacing the factors from the ribosome after the release of peptide.

PMID- 9233823
TI  - Bacteriophage T4 UvsW protein is a helicase involved in recombination, repair and
      the regulation of DNA replication origins.
AB  - Bacteriophage T4 UvsW protein is involved in phage recombination, repair and the
      regulation of replication origins. Here, we provide evidence that UvsW functions
      as a helicase. First, expression of UvsW allows growth of an (otherwise inviable)
      Escherichia coli recG rnhA double mutant, consistent with UvsW being a functional
      analog of the RecG helicase. Second, UvsW contains helicase sequence motifs, and
      a substitution (K141R) in the Walker 'A' motif prevents growth of the E.coli recG
      rnhA double mutant. Third, UvsW, but not UvsW-K141R, inhibits replication from a
      T4 origin at which persistent RNA-DNA hybrids form and presumably trigger
      replication initiation. Fourth, mutations that inactivate UvsW and endonuclease
      VII (which cleaves DNA branches) synergistically block repair of double-strand
      breaks. These in vivo results are consistent with a model in which UvsW is a DNA
      helicase that catalyzes branch migration and dissociation of RNA-DNA hybrids. In
      support of this model, a partially purified GST/UvsW fusion protein, but not a
      GST/UvsW-K141R fusion, displays ssDNA-dependent ATPase activity and is able to
      unwind a branched DNA substrate.

PMID- 9233824
TI  - Modulatory influence of arecoline on the phytic acid-altered hepatic
      biotransformation system enzymes, sulfhydryl content and lipid peroxidation in a
      murine system.
AB  - The potential of arecoline alkaloid, by direct or translactational exposure, to
      modify the chemopreventive efficacy of phytic acid, via modulation of hepatic
      biotransformation system enzymes and antioxidant defence mechanism, was assessed
      in a murine system. Phytic acid (500 or 1000 mg/kg b.w. per day) induced a
      statistically significant increase in the hepatic levels of glutathione S
      transferase (GST) and sulfhydryl (-SH) in murine females and suckling neonates.
      The elevated levels of hepatic cytochrome b5 (Cyt. b5), cytochrome P-450 (Cyt. P
      450) and the depleted level of malondialdehyde (MDA) were observed in the
      lactating mice. Arecoline (20 mg/kg b.w. per day) alone did not modulate the
      hepatic GST and -SH levels although it induced a statistically significant
      increase in the levels of Cyt. b5, Cyt. P-450 and MDA in the murine system.
      Phytic acid-modulated hepatic levels of phase II components were depressed
      whereas phase I enzymes and lipid peroxides were further elevated by arecoline
      plus-phytic acid treatment. The implications of direct or translactational
      modulation in the competing potential pathways of biotransformation system
      enzymes in the process of chemical carcinogenesis are discussed.

PMID- 9233822
TI  - Fast recycling of Escherichia coli ribosomes requires both ribosome recycling
      factor (RRF) and release factor RF3.
AB  - A complete translation system has been assembled from pure initiation, elongation
      and termination factors as well as pure aminoacyl-tRNA synthetases. In this
      system, ribosomes perform repeated rounds of translation of short synthetic mRNAs
      which allows the time per translational round (the recycling time) to be
      measured. The system has been used to study the influence of release factor RF3
      and of ribosome recycling factor RRF on the rate of recycling of ribosomes. In
      the absence of both RF3 and RRF, the recycling time is approximately 40 s. This
      time is reduced to approximately 30 s by the addition of RF3 alone and to
      approximately 15 s by the addition of RRF alone. When both RF3 and RRF are added
      to the translation system, the recycling time drops to <6 s. Release factor RF3
      is seen to promote RF1 cycling between different ribosomes. The action of RRF is
      shown to depend on the concentration of elongation factor-G. Even in the presence
      of RRF, ribosomes do not leave the mRNA after termination, but translate the same
      mRNA several times. This shows that RRF does not actively eject mRNA from the
      terminating ribosome. It is proposed that terminating ribosomes become mobile on
      mRNA and ready to enter the next translation round only after two distinct steps,
      catalysed consecutively by RF3 and RRF, which are slow in the absence of these
      factors.

PMID- 9233826
TI  - A case-control study of risk factors of nasopharyngeal carcinoma.
AB  - Risk factors and nasopharyngeal carcinoma (NPC) in residents of Guangzhou city
      were investigated in a case-control study: 104 cases were compared with an equal
      number of age, sex, and neighborhood-matched controls. The results of multiple
      conditional regression of logistic model showed that plum vegetable (adjusted OR
      = 1.81, 95% CI 1.01-3.33), preserved prune (adjusted OR = 2.95, 95% CI 1.04
      8.41), no separate kitchen (if >35 years, adjusted OR = 1.98, 95% CI 1.24-3.75),
      kitchen range without chimney (if >10 years, adjusted OR = 2.72, 95% CI 1.56
      4.73) and hereditary factor (adjusted OR = 8.27, 95% CI 1.94-35.54) were
      significantly associated with an increased risk of NPC. Grape (adjusted OR =
      0.31, 95% CI 0.17-0.58) may be a protective factor.

PMID- 9233825
TI  - Molecular non-genetic biomarkers of effect related to acephate cocarcinogenesis:
      sex- and tissue-dependent induction or suppression of murine CYPs.
AB  - The aim of this work was to study the ability of the organophosphate insecticide
      acephate to alter some biochemical markers of effect related non-genetic
      cocarcinogenesis. For this purpose, selective CYP-dependent reactions have been
      examined in liver, kidney and lung microsomes of male and female Swiss albino CD1
      mice treated (i.p.) with a 125 or 250 mg/kg b.w. dose of this pesticide. High
      specific substrates were used as a probe of various isozymes, such as CYP 1A1,
      1A2, 2B1, 2E1 and 3A. Maked organ- and sex-related differences in either inducive
      or suppressive response by acephate depict a complex pattern of CYP modulation
      with the kidney being more responsive to 3A induction (up to 6.9-fold increase,
      male) and the lung to 2B1 suppression (up to 70% loss, mainly female). In the
      liver, a 2.7-fold increase in the 3A-like activity, probed by the O-demethylation
      of aminopyrine, in the O-deethylation of phenacetin (1.8-fold increase, 1A2), as
      well as in the hydroxylation of p-nitrophenol (1.6-fold increase, 2E1) was
      observed in male animals at a lower dose. In contrast, a marked reduction of CYP
      1A1-mediated ethoxyresorfin O-deethylase activity ranging from 43% (lower dose)
      to 44% loss (higher dose) in female and male mice, respectively, and of CYP 2B1
      mediated pentoxyresorufin O-dealkylase (3% loss, female) was achieved. In the
      kidney, an increase in the 'mixed' ethoxycoumarin O-deethylase (up to 2-fold) as
      well as in the 2B1-like activity (up to 2.8-fold) was also recorded in males at
      250 mg/kg. Once again, in the lung, a different behaviour on 3A isoforms between
      female (approximately 2-fold increase) and male (44% loss) was seen at a lower
      dose. The specificity of CYP changes was corroborated by means of Western
      immunoblotting analysis using rabbit polyclonal antibodies, anti-CYP 3A1/2 and
      2E1. Taken together, these data indicate a possible toxic/cotoxic, cocarcinogenic
      and promoting potential of acephate.

PMID- 9233827
TI  - The ribosomal 5.8S RNA as a target site for p53 protein in cell differentiation
      and oncogenesis.
AB  - Previous studies have shown that the ribosomal 5.8S rRNA of human cells is
      partially methylated in a tissue-specific fashion, a modification which occurs
      largely or entirely in the cytoplasm. More recent studies have shown that the
      5.8S rRNA forms a covalent linkage with tumor suppressor p53 protein and have
      suggested that this RNA plays a functional role in protein elongation. We now
      show that the expression of p53 protein in Schizosaccharomyces pombe results in
      cells which: morphologically resemble transformed cells expressing mutant 5.8S
      rRNA; are equally compromised in their ability to sustain protein synthesis, in
      vitro; and contain polyribosome profiles which strongly resemble the elevated
      profiles which also are observed with mutated 5.8S rRNA. Taken together, these
      results provide new physiological evidence of the possibility that the 5.8S rRNA
      is an important target in the control of ribosome function during cell
      differentiation and oncogenesis.

PMID- 9233828
TI  - Constitutive endonuclease to induce high molecular weight or internucleosomal DNA
      fragmentation in freshly isolated leukemia cells.
AB  - Using an autodigestion method, we investigated endogenous endonuclease(s) in
      leukemia cells freshly obtained from pediatric patients with various types of
      leukemia. Endonucleolytic activity was found to cause both high molecular weight
      and internucleosomal DNA fragmentation at a neutral pH in whole cell lysates of
      all common acute lymphoblastic leukemia (cALL) blasts, which was Mg2+-dependent
      and Ca2+-independent. Whole lysates from most acute myeloblastic leukemia (AML)
      cells possessed similar endonuclease activity, but both Mg2+ and Ca2+ were
      required for the activity. Our results suggest that leukemia cells of different
      lineages have distinct constitutive endonucleases, which may play a role in the
      occurrence of apoptosis in these cells.

PMID- 9233829
TI  - Induction of differentiation and apoptosis by sodium selenite in human colonic
      carcinoma cells (HT29).
AB  - To explore the mechanism(s) by which selenium (Se) exerts its cancer
      chemopreventive activity, we studied the effect of selenite (0-100 microM) on
      cell growth, viability, differentiation, detachment, DNA fragmentation and
      apoptosis in human colonic carcinoma cells (HT29). Selenite (>5 microM) decreased
      cell growth, increased cell detachment and decreased intracellular levels of
      reduced glutathione (GSH), whereas >10 microM selenite induced cell
      differentiation and apoptosis. The chemopreventive effects of selenite may be
      related in part to the generation of reactive oxygen species (ROS) resulting from
      the reaction between selenite and GSH.

PMID- 9233830
TI  - TGFbeta regulation of mitogen-activated protein kinases in human breast cancer
      cells.
AB  - We demonstrate herein the ability of transforming growth factor-beta-2 (TGFbeta2)
      to potently activate extracellular signal-regulated kinase 2 (ERK2) in the highly
      TGFbeta-sensitive breast cancer cell (BCC) line Hs578T. The ERK2 isoform was
      activated by 3-fold within 5 min of TGFbeta2 addition to Hs578T cells. However,
      TGFbeta2 only slightly activated ERK2 (1.5-fold) in the partially TGFbeta
      responsive BCC line MDA-MB-23 1. The magnitude of the difference in activation of
      ERK2 by TGFbeta2 in the two cell lines paralleled the difference in the IC50
      values for TGFbeta inhibition of DNA synthesis; the IC50 value in the MDA-MB-231
      cells was 32-fold greater than that in the Hs578T cells. Further, our data
      demonstrate that TGFbeta2 activated the stress-activated protein kinase/Jun N
      terminal kinase (SAPK/JNK) type of mitogen-activated protein kinases (MAPKs);
      maximal induction levels were 2.5-fold above basal values and were attained at 30
      min after TGFbeta2 treatment. Transient co-transfection of a luciferase reporter
      construct (3TP-Lux) containing three AP-1 sites and the plasminogen activator
      inhibitor-1 (PAI-1) promoter, in conjunction with a construct that directs
      expression of a dominant-negative mutant ERK2 (TAYF) protein, did not block the
      ability of TGFbeta to induce AP-1 or PAI-1 activity. In contrast, TAYF ERK2 was
      able to block EGF and insulin-induced 3TP-Lux-reporter activity. These results
      indicate that in these BCCs, the activation of ERK2 by TGFbeta is more tightly
      linked to the ability of TGFbeta to inhibit DNA synthesis than to the ability to
      stimulate promoter regions important for TGFbeta production and control of the
      extracellular matrix. In addition, this is the first demonstration that TGFbeta
      can activate the SAPK/JNK type of MAPK in TGFbeta-sensitive human BCCs.

PMID- 9233831
TI  - Plasmin induces the formation of multicellular spheroids of breast cancer cells.
AB  - MCF7 and ZR75-1 breast cancer cells grow as adherent monolayers in tissue
      culture. Treatment with the serum serine protease plasmin causes them to detach
      and to grow as floating multicellular spheroids. Two plasmin activators,
      urokinase plasminogen activator and streptokinase, induce the same growth pattern
      changes in the presence of plasminogen. Serum contains also plasminogen activator
      inhibitors. Aged serum, deficient in plasminogen activator inhibitors, converts
      spontaneously monolayer breast cancer cells into multicellular spheroids which
      readily revert to monolayer growth after addition of fresh serum. Urokinase
      blocks the reversion. The formation of multicellular spheroids does not affect
      the proliferative rate of breast tumor cells but endows tumor cells with
      increased resistance to the chemotherapeutic drugs, doxorubicin and paclitaxel.

PMID- 9233832
TI  - Suppression of tumor growth by the 3' untranslated region of mel-18 in 3Y1 cells
      transformed by the E6 and E7 genes of human papillomavirus type 18.
AB  - By introducing a cDNA library derived from rat embryonic fibroblast cells, we
      isolated several morphologically flat revertants of rat 3Y1 cells transformed by
      the E6 and E7 genes of human papillomavirus type 18 (HPV18). From one of the
      revertants, we recovered a 0.2-kb cDNA, N56, that suppresses the tumor growth of
      the transformed 3Y1 cells irrespective of the expression of the E6 and E7 genes.
      The nucleotide sequence of the cDNA was shown to be identical to that of the 3'
      untranslated region of a putative mammalian polycomb group gene, mel-18.

PMID- 9233833
TI  - Increased telomerase activity is not directly related to metastatic potential in
      rat transplantable osteosarcomas.
AB  - Previously, we reported the establishment of two transplantable osteosarcomas in
      rats, one induced by local application of a carcinogen, 4-hydroxyamino quinoline
      1-oxide (4-HAQO), and another which developed spontaneously, and their
      subdivision into four lines with high and low metastatic potential to the lung.
      In the present study, activation of telomerase was investigated by the telomeric
      repeat amplification protocol (TRAP) assay followed by densitometric
      quantification. Telomerase activity was found to be elevated in all four lines
      without any link to the metastatic potential. Thus the spontaneous osteosarcoma
      (SOS) and derived metastatic lesions (S-SLM) demonstrated a 20.1-23.5-fold
      increase and the chemical carcinogen (4HAQO)-induced osteosarcoma (COS) and
      metastatic lesions (C-SLM) were 18.4-19.1-fold elevated as compared to the value
      for abdominal muscle. The results suggest that activation of telomerase occurs in
      rat osteosarcomas but that it is not directly involved in determining their
      metastatic potential.

PMID- 9233834
TI  - Inducible antisense inhibition of erbB-2 expression reduces anchorage independent
      growth of ovarian carcinoma cells.
AB  - We have investigated the effect of c-erbB-2 expression on the growth of ovarian
      carcinoma cell lines using antisense methodology. A 1.5 kb fragment of c-erbB-2
      cDNA was cloned in an antisense and sense orientation into an IPTG inducible
      vector. These vectors were stably transfected into two ovarian carcinoma cell
      lines, one of which (NIH:OVCAR-8) grew well in soft agar. Inhibition of
      expression of endogenous c-erbB-2 protein was detected by immunoprecipitation and
      Western blot in both of the induced transfectants with the antisense construct.
      Although growth in monolayer culture was unaffected, NIH:OVCAR-8 cells
      transfected with the antisense construct and induced with IPTG lost their ability
      to form colonies in soft agar. Consequently, endogenous expression of c-erbB-2
      modulates anchorage-independent growth of NIH:OVCAR-8.

PMID- 9233835
TI  - p53 gene mutation in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary
      bladder tumors and N-methyl-N-nitrosourea-induced colon tumors of rats.
AB  - We analyzed p53 mutations in 17 N-butyl-N-(4-hydroxybutyl) nitrosamine-induced
      bladder transitional cell carcinomas (TCCs) with or without areas of squamous
      cell carcinoma (SCC) of Long-Evans Cinnamon (LEC) and F344 rats, and in 7 N
      methyl-N-nitrosourea-induced colon adenocarcinomas of LEC rats by polymerase
      chain reaction-single strand conformation polymorphism analysis and DNA
      sequencing. Of these bladder tumors, one TCC with moderately differentiated SCC
      had a T to G transversion mutation at codon 141, leading to a Val to Gly amino
      acid change. No p53 mutation was found in colon adenocarcinomas. Thus a p53 gene
      mutation seems infrequent in these rat bladder and colon carcinogenesis models
      even in the late stage.

PMID- 9233836
TI  - Oxidative DNA damage in tissues of pregnant female mice and fetuses caused by the
      tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK).
AB  - The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK), induces the promutagenic oxidative-damage DNA lesion, 8-oxo-2'
      deoxyguanosine (8-oxo-dG), in adult animals. To investigate whether this
      alteration occurs in DNA after transplacental exposure, pregnant Swiss mice were
      administered single or multiple doses of NNK. The 8-oxo-dG was quantified in
      placenta, and maternal and fetal tissues. In maternal lungs, single and multiple
      doses of NNK significantly increased levels of 8-oxo-dG by 23% and 32%,
      respectively. In maternal liver, a significant 38% increase was observed after
      multiple dose treatment. In the fetuses, a significant 45% increase in 8-oxo-dG
      levels was observed in liver after multiple doses of NNK. This is the first
      demonstration of oxidative DNA damage after transplacental exposure to NNK, and
      supports the concept of maternal smoking as a contributor to the development of
      childhood cancer.

PMID- 9233837
TI  - Norcantharidin inhibits growth of human HepG2 cell-transplanted tumor in nude
      mice and prolongs host survival.
AB  - In this study, norcantharidin was compared with adriamycin and mitomycin C for
      its inhibitory action in the growth of cultured human hepatocellular carcinoma
      HepG2 cells. The IC50 of adriamycin and mitomycin C on HepG2 cells was 7.3 microM
      and 27 microM, respectively, whereas the IC50 of norcantharidin for inhibiting
      the growth of HepG2 cells was as high as 1900 microM. After HepG2 tumor-bearing
      nude mice were treated with 12 daily intraperitoneal injections of norcantharidin
      (2 mg/kg), the increase in tumor size was significantly slower than that of
      untreated controls. The mean survival time of untreated tumor-bearing nude mice
      was 129 days, whereas in the tumor-bearing nude mice treated with norcantharidin,
      the mean survival time was significantly prolonged to 194 days (P < 0.0001). It
      is concluded that norcantharidin may have a potential role in the treatment of
      human hepatocellular carcinoma.

PMID- 9233838
TI  - d-Limonene inhibits N-nitrosobis(2-oxopropyl)amine induced hamster pancreatic
      carcinogenesis.
AB  - The effect of d-limonene on pancreatic carcinogenesis induced by N-nitrosobis(2
      oxopropyl)amine (BOP) was investigated in Syrian golden hamsters. During and
      after 5 weekly injections of BOP, each hamster was fed diet containing d
      limonene. In week 26, quantitative histological analysis showed that prolonged
      treatment with d-limonene significantly reduced the number of pancreatic
      carcinomas. Administration of d-limonene did not cause a significant increase in
      the apoptotic index, but caused a significant decrease in the BrdU labeling index
      of carcinoma. These findings indicate that d-limonene inhibits the development of
      pancreatic carcinoma not by enhancing tumor cell loss through apoptosis, but
      rather by inhibiting cell proliferation.

PMID- 9233839
TI  - Activity and distribution of the cysteine prodrug activating enzyme, 5-oxo-L
      prolinase, in human normal and tumor tissues.
AB  - 5-Oxo-L-prolinase (OPase), a key enzyme of the gamma-glutamyl cycle, has the
      ability to metabolize L-2-oxothiazolidine-4-carboxylic acid (OTC) to cysteine,
      and thereby increase intracellular glutathione (GSH) levels. This strategy of GSH
      elevation can be potentially exploited to reduce normal tissue toxicity of
      anticancer agents, provided that sufficient differences exist in OPase levels
      between normal and malignant tissues. In this study, therefore, we quantitated
      OPase activity in primary specimens of matched and unmatched human normal and
      tumor (lung, breast, kidney, colon and ovary) tissues using a newly developed non
      radioactive OPase assay, based on the production of cysteine from OTC. The rank
      order of OPase activity in extracts of 24 normal tissues examined was kidney >
      lung, breast and colon > ovary. OPase activity was present in all 37 tumor
      samples, but at variable levels. Tumor OPase levels were generally equivalent to
      those in their normal tissue counterparts, with the notable exception of Wilms'
      tumors, which had markedly lower levels than normal kidney (P < 0.02). However,
      when 14 matched tumor and adjacent normal tissues were compared, OPase levels
      were significantly higher in normal specimens than tumors for individual patients
      (P < 0.005). These higher normal tissue/tumor OPase ratios suggest that OTC may
      be useful in decreasing normal tissue toxicity, at least, for some tissues during
      cancer therapy.

PMID- 9233841
TI  - Stereological study of acinar growth in the rat parotid gland induced by
      isoproterenol.
AB  - The growth of the rat parotid gland induced by daily treatment with isoproterenol
      (IPR) for 2 weeks was investigated by stereological methods applied to light
      microscopy. After 7 days of treatment, the glandular mass presented a 286%
      growth, with the first 3 days being the period of greatest growth. Total acinar
      volume exhibited a 363% increase during the period from 0 to 7 days, while acinar
      cell volume presented a 468% growth from 0 to 5 days of treatment. On the other
      hand, total acinar-cell number did not increase during the study period. Thus,
      under the conditions used, IPR-stimulated gland growth was essentially
      hypertrophic. However, a significant increase in the number of bipolar and
      multipolar mitoses was also observed, especially on the third and fifth days of
      treatment. As no increase in acinar-cell number occurred during growth, the
      presence of these mitoses suggests that cell death occurred during gland growth.
      On this basis, bipolar mitoses may occur to replace cells that probably
      degenerated during treatment, whereas multipolar mitoses may lead to the
      occurrence of polyploidy.

PMID- 9233840
TI  - Skin carcinogenicity of condensed asphalt roofing fumes and their fractions
      following dermal application to mice.
AB  - Condensed roofing asphalt fumes, generated at 316 degrees C, were collected by
      cold trap condensation and fractionated by preparative high performance liquid
      chromatography. Chemical classes in each of the fractions (A-E) were identified
      by gas chromatography/mass spectroscopy. The fractions, various combinations of
      fractions, the raw and heated asphalt, the neat asphalt fume and the
      reconstituted asphalt were tested for carcinogenicity, and three fractions were
      tested for cocarcinogenicity and tumor promotion with benzo[a]pyrene (BaP). The
      skin application carcinogenesis bioassay was conducted by twice weekly
      application of test materials in 0.05 ml of acetone/cyclohexane (1:1) for 104
      weeks to 40 groups of male C3H/HeJ mice (30/group). Fractions were applied at a
      mass in proportion to their amount in the neat asphalt fumes. In addition, the
      neat asphalt fume was tested on Sencar mice to determine if this strain was more
      susceptible to the carcinogenic effects of the fumes. Condensed neat asphalt
      fumes produced similar and statistically significant increased tumor yields of
      papillomas and carcinomas in both strains as compared to respective vehicle
      controls. Recombination of all fractions resulted in a tumor response similar to
      neat asphalt fumes. Among individual fractions, C was most potent, followed by B.
      The other single fractions were without significant tumorigenic activity.
      Combinations containing fractions B and C were most active among the mixtures
      that were assayed and no evidence of enhancement of tumorigenesis in the mixtures
      was found. No significant cocarcinogenic or tumor promoting activity was observed
      with fractions A, D, or E and BaP. Raw unheated asphalt produced a few tumors in
      C3H mice, but no tumors were seen when raw asphalt heated to 316 degrees C, with
      the fumes permitted to escape, was applied.

PMID- 9233843
TI  - Spline analysis of the mandible in human subjects with class III malocclusion.
AB  - This study determines deformations that contribute to a Class III mandibular
      morphology, employing thin-plate spline (TPS) analysis. A total of 133 lateral
      cephalographs of prepubertal children of European-American descent with either a
      Class I molar occlusion or a Class III malocclusion were compared. The
      cephalographs were traced and checked, and eight homologous landmarks on the
      mandible were identified and digitized. The datasets were scaled to an equivalent
      size and subjected to statistical analyses. These tests indicated significant
      differences between average Class I and Class III mandibular morphologies. When
      the sample was subdivided into seven age and sex-matched groups statistical
      differences were maintained for each group. TPS analysis indicated that both
      affine (uniform) and non-affine transformations contribute towards the total
      spline, and towards the average mandibular morphology at each age group. For non
      affine transformations, partial warp 5 had the highest magnitude, indicating
      large-scale deformations of the mandibular configuration between articulare and
      pogonion. In contrast, partial warp 1 indicated localized shape changes in the
      mandibular symphyseal region. It is concluded that large spatial-scale
      deformations affect the body of the mandible, in combination with localized
      distortions further anteriorly. These deformations may represent a developmental
      elongation of the mandibular corpus antero-posteriorly that, allied with
      symphyseal changes, leads to the appearance of a Class III prognathic mandibular
      profile.

PMID- 9233842
TI  - Immunostaining and transcriptional enhancement of interleukin-1 receptor type I
      in the rat dental follicle.
AB  - Interleukin-1alpha (IL-1alpha) enhances the gene expression of colony-stimulating
      factor-one (CSF-1) in dental follicle cells. In turn, CSF-1 appears to be a
      critical molecule in stimulating the cellular events of eruption that require the
      presence of the follicle. Chronologically, the maximal transcription and
      translation of CSF-1 in the follicle occurs early postnatally, followed by a
      decline later. Thus, in this study, immunostaining for the interleukin-1 receptor
      type I (IL-1RI) was used to determine if it paralleled the CSF-1 localization and
      chronology. The results showed that IL-1RI is primarily localized in the dental
      follicle, with maximal immunostaining early postnatally and a greatly reduced
      staining by day 10. In conjunction with this, molecules that enhance the gene
      expression of IL-1alpha epidermal growth factor (EGF) and transforming growth
      factor-beta1 (TGF-beta1) were also shown to enhance the expression of IL-1RI, but
      IL-1alpha did not increase the gene expression of IL-1RI. After injections of EGF
      at different times postnatally the mRNA of IL-1RI increased over comparable
      controls. Between days 2 and 5 the IL-1RI mRNA in the follicle decreased. In
      combination the results suggest that, as the expression of IL-1alpha is enhanced
      in the stellate reticulum either by EGF or TGF-beta1, these two molecules could
      also enhance the expression of IL-1RI in the dental follicle such that more
      receptors would be available to respond to the increased IL-1alpha secreted. The
      maximal presence of the receptors (IL-1RI) in the dental follicle early
      postnatally, followed by their subsequent decline, parallels the rise and fall of
      CSF-1 in the follicle. Thus, regulation of the IL-1RI and IL-1RI gene expression
      might be a means of regulating changes in CSF-1 in the follicle.

PMID- 9233845
TI  - Statistical evaluation of Monson's sphere in healthy permanent dentitions in man.
AB  - The three-dimensional curvature of the mandibular dental arch was studied in 20
      men and 20 women with sound dentitions and free from temporomandibular joint
      problems. The x, y, z coordinates of cusp tips of all but the third molars were
      obtained with a three-dimensional digitizer, and used to derive a spherical model
      of the curvature of the occlusal surfaces. From the best interpolating sphere the
      radii of the left and right curves of Spee (quasi-sagittal plane) and of the
      canine and molar curves of Wilson (frontal plane) were computed. The occlusal
      curvature of the mandibular arch was not significantly influenced by gender, even
      if, on average, all the computed variables were larger in men than women. The
      radii of the overall sphere, right and left curves of Spee, and curve of Wilson
      in the molar area were about 105 mm in men, and about 100 mm in women. A
      relatively large intrasample variability in arch curvature was found. The mean
      sphere radius in men was very close to the classical value of 4 in, confirming
      Monson's observations, but the relatively large intrasample variability prevented
      any definitive determination of a sexual dimorphism in the three- dimensional
      characteristics of occlusal curvature.

PMID- 9233844
TI  - Glycosaminoglycan biosynthesis during 5-fluoro-2-deoxyuridine-induced palatal
      clefts in the rat.
AB  - The biosynthesis and hydration of glycosaminoglycans (GAG) has been implicated in
      the generation of palatal shelf-elevating force(s) in mammals, although the
      nature of the palatal shelf extracellular matrices during cleft palate formation
      remains poorly understood. This study quantifies the GAG composition in the
      palatal shelves of Wistar rat fetuses at various periods of palatogenesis where
      clefts were induced experimentally using 5-fluoro-2-deoxyuridine (FUDR). For both
      normal and cleft palatal shelves, hyaluronan, heparan sulphate and chondroitin-4
      sulphate were detected but not dermatan sulphate or chondroitin-6-sulphate.
      Throughout the period of cleft development studied, the total amount of GAG was
      significantly decreased (by approx. 30%) compared with normal development, this
      decrease being particularly marked at a time equivalent to post-elevation during
      normal development (approx. 75%). Furthermore, and unlike normal palatogenesis,
      no significant differences were recorded between the anterior and posterior parts
      of the palatal shelves during cleft formation. As for normal palatogenesis,
      however, the percentages of each GAG were not altered at any stage. The findings
      are consistent with the view that suppression of GAG biosynthesis is related to
      the development of cleft palate in FUDR-treated rat fetuses and can therefore be
      interpreted as providing evidence of a role for the mesenchymal glycoconjugates
      in shelf elevation during normal palatogenesis.

PMID- 9233846
TI  - A new method for eliciting and studying H-reflexes in the human masseter.
AB  - A non-invasive method is presented for transmuscular stimulation of the
      masseteric nerve, using a frame to apply a cathode to the mandibular notch and an
      anode to the inside of the mouth. The H-reflex response was recorded using
      surface, macro and single motor-unit (SMU) electromyography (EMG) from the
      masseter. The latency of the reflex response representing the H-reflex in SMUs
      was determined from the cumulative sum of the peristimulus time histogram. This
      latency was then corrected using a spike-trigger averaging technique, where the
      SMU spikes were used as triggers and the macro EMG recording as the source. SMU
      latencies for the H-reflex in masseter were in the range 5.9-8.8 msec, whereas H
      reflex latencies for surface EMG varied between 5.4 and 6.4 msec.

PMID- 9233847
TI  - Effects of iron salts in sucrose on dental caries and plaque in rats.
AB  - Anaemia caused by iron deficiency and dental caries are still among the most
      prevalent diseases in some developing countries. Anaemia can be prevented by iron
      fortification of food. Previous studies demonstrated that iron-sucrose, which has
      been used for prevention of anaemia, reduces the incidence of caries in rats. The
      aim of the present study was to compare the influence of ferrous sulphate and
      ferric glycerophosphate co-crystallized with sucrose on the incidence of dental
      caries in rats. Forty-eight desalivated rats were caged in a programmed feeder
      and received their essential nutrition by gavage. The animals were fed 17 meals
      per day at hourly intervals of 88 parts/10(6) Fe++ or Fe co-crystallized with
      sucrose. Plain sucrose and calcium glycerophosphate with sucrose were used as
      control groups. Both ferric- and ferrous-sucrose meals reduced the incidence of
      smooth-surface and sulcal caries in rats. Stain formation, organic acid
      production and acidogenic activity of dental plaque in animals receiving iron
      sucrose meals were also investigated. Ferric glycerophosphate did not induce
      extrinsic staining on the tooth surface. The concentration of organic acids did
      not differ significantly among the groups. The acidogenic activity of plaque in
      animals receiving either of the iron-sucrose meals tended to be lower than that
      of the control groups. The possibility that iron-sucrose might reduce the
      prevalence of two major public health problems, dental caries and anaemia, makes
      this preventive approach extremely attractive for additional investigation.

PMID- 9233848
TI  - Distribution of transforming growth factor beta1-binding proteins and low
      affinity receptors during odontoblast differentiation in the mouse.
AB  - Transforming growth factor-beta1 (TGF-beta1) was immunolocalized within
      differentiated odontoblasts and ameloblasts while LAP-beta1 was detected at the
      apicol pole of odonotoblasts and ameloblasts and in predentine. Anti-LAP-beta1
      antibodies also stained the epithelial-mesenchymal junction (EMJ). Decorin was
      immunolocalized in young functional odonotoblasts and in both predentine and
      dentine. Biglycan was similarly distributed but absent from dentine.
      Immunostaining with anti-latent TGF-beta1 binding protein-1 (LTBP-1) showed
      fibrillar structures located at the EMJ and between predontoblasts and
      odontoblasts; at older states staining was restricted to the dental papilla and
      sac. Thus differentiated odonotoblasts express TGF-beta1 and in a more restricted
      manner decorin, biglycan and LAP-beta1; it can be assumed that TGF-beta1 is able
      to interact with the three molecules present in predentine. Earlier, LTBP-1 and
      LAP-beta1, both present at the EMJ, may contribute to odontoblast
      differentiation.

PMID- 9233849
TI  - Effects of extracellular ATP on cytosolic Ca2+ concentration and secretory
      responses in rat parotid acinar cells.
AB  - At concentrations >50 microM, extracellular ATP dose-dependently increased
      cytosolic Ca2+ concentration ([Ca2+]i) via activation of P(2Z) purinoceptors in
      rat parotid acinar cells. This increase in [Ca2+]i is primarily due to entry of
      Ca2+ from the extracellular medium. Inositol trisphosphate formation and Ca2+
      release from intracellular Ca2+ stores were slightly stimulated by ATP. These
      responses seem to result from the activation of a P2 purinoceptor subtype
      different from P(2Z) because the maximum responses were induced by much lower
      concentrations ( <0.25 mM) of ATP than those (> 1 mM) required to produce the
      maximum activation of Ca2+ entry. ATP did not stimulate amylase release,
      supporting the view that an increase in [Ca2+]i is not a sufficient stimulus. In
      addition, ATP evoked a marked K+ release in the presence and absence of
      extracellular Ca2+, while in carbachol-stimulated cells. only a transient release
      of K+ was observed in the absence of extracellular Ca2+. The ATP-induced K+
      release may be mediated by a mechanism independent of the opening of the Ca(2+)
      sensitive K+ channels.

PMID- 9233850
TI  - Sequence of eruption of deciduous dentition in a Chilean sample with Down's
      syndrome.
AB  - The eruption of the deciduous teeth in Down's individuals is reportedly delayed,
      but the extent of delay in comparison to normal children has been little studied.
      The eruption characteristics of the deciduous teeth in a sample of Chilean
      individuals with Down's syndrome were compared with those of the normal Chilean
      population. The sample consisted of 255 Down's individuals (all with trisomy 21),
      127 males and 128 females. Boys with Down's syndrome showed significantly delayed
      eruption in six teeth: in the maxilla the right central incisor and right and
      left lateral incisors, and in the mandible the right central incisor and right
      and left canines. Girls with Down's syndrome showed significant delays in the
      eruption of 11 teeth: in the maxilla the right and left lateral incisors, right
      and left canines and first left molar, and in the mandible the left central
      incisor, right and left lateral incisors and canines and second right molar. The
      chronological sequence of eruption in Down's children was not completely
      different from that of normal individuals. With a few exceptions no significant
      departures from Gaussian distribution were found in the age of eruption among
      both normal and Down's individuals. The variance was significantly larger in
      cases of Down's syndrome.

PMID- 9233851
TI  - Accounting for handicaps in aphasia: communicative assessment from an authentic
      social perspective.
AB  - The ICIDH classification system has had an important effect on many areas of
      rehabilitation. In this article an application of the handicap category of the
      ICIDH system within the assessment of aphasia is described. This assessment
      procedure, Communicative Profiling System, provides an example of how detailed
      and authentic examination of complex social phenomena can be accomplished. A case
      study and implications of this procedural application are provided.

PMID- 9233852
TI  - Auditory comprehension problems in aphasia from the perspective of aphasic
      persons and their families and friends.
AB  - This study explored with a qualitative approach the experience of auditory
      comprehension problems from the perspective aphasic persons and their families
      and friends. Semi-structured group interviews were held with 55 persons (29
      aphasic and 26 non-aphasic) who were asked to describe the consequences of
      aphasia on their lives. Most participants contributed some material to the topic
      of interest. They described problematic situations, and the behaviours they said
      they adopted at those times; they also provided explanations of what their
      problems were. Some discrepancies between aphasic persons and their families and
      friends were also noted. The essential elements of the experience of an auditory
      comprehension problem centre around speakers' rate of speech and situations in
      which aphasic persons feel they are incapable of understanding or of following
      because of an unfavourable environment.

PMID- 9233853
TI  - A new perspective on the relationship between communication impairment and
      disempowerment following head injury in information exchanges.
AB  - Communication disorders following closed head injury (CHI) have been described in
      terms of the impairments that affect the individual's ability to produce words,
      sentences and discourse. Rather than focusing on impairments, this paper examines
      the disability experienced by one CHI subject. Comparison is made between M. R.,
      who has sustained a severe CHI, and his brother, S. R. during four telephone
      calls to their mother, a therapist, the police and the bus timetable information
      service, using exchange structure analysis. Results indicated that social
      distance between communication partners, and the nature of the interaction,
      affected the language choices made by both subjects. The communication partner
      was found to have a profound impact on the way each subject was able to negotiate
      each interaction. Results are discussed in terms of the ways in which therapists
      and society in general view disability and how this shapes social encounters,
      which in turn affects the outcomes which are made possible for people with CHI.

PMID- 9233854
TI  - Interactions between recovery in aphasia, emotional and psychosocial factors in
      subjects with aphasia, their significant others and speech pathologists.
AB  - Associations between clinical and functional aphasia recovery and perceptions of
      emotional and psychosocial adjustment accompanying aphasia were examined in five
      subjects at 3 and 9 months post-onset of stroke using a range of objective and
      subjective measures. The subjective well-being and optimism of significant others
      of aphasic patients was also examined, and speech pathologists completed measures
      of optimism. Unique patterns of individual emotional and psychosocial adjustment
      were found over time in patients and their significant others, even in patients
      with similar aphasia type and severity. Individual variability in emotional and
      psychosocial adjustment and their impact on recovery from aphasia are discussed.

PMID- 9233855
TI  - Time to talk: counselling for people with dysphasia.
AB  - In this small-scale qualitative study, 20 dysphasic people, including some with
      severe language impairments, were offered up to 20 sessions of individual
      counselling. The trained counsellors were a speech and language therapist and a
      teacher who had personal experience of dysphasia. The paper describes how the
      service was set up, and how it was evaluated through the use of interviews
      before, during and after the process of counselling. In general, participants
      valued the service and a number of positive outcomes were described. Negative
      reactions were largely due to problems with the setting, timing and organization
      of the counselling and to the presence of social problems which could not be
      addressed through counselling. A number of recommendations for setting up a
      counselling service for people with dysphasia can be drawn from this study. These
      are discussed in this paper, together with the issues arising from the
      collaboration between dysphasic and non-dysphasic researchers.

PMID- 9233856
TI  - Conceptual considerations in head & neck reconstruction. Defect analysis and
      options for reconstruction.
AB  - This article reviews the authors' approach to the management of facial defects
      based on extensive experience in facial reconstruction. The article describes
      basic principles of wound healing with attention to healing by secondary
      intention and its role in facial reconstruction. Detailed consideration is
      provided for various options of repair of facial defects including primary
      closure, grafting, and local flap techniques.

PMID- 9233857
TI  - Concepts in scalp and forehead reconstruction.
AB  - Reconstruction of forehead and scalp defects are challenging. A thorough
      understanding of the anatomy and dissection planes of the scalp is essential. The
      ability to use a variety of techniques allows the facial plastic surgeon to
      maximize functional and aesthetic results. Techniques such as tissue expansion,
      free tissue transfer, and flaps used for covering exposed bone are useful
      adjuncts for optimal results.

PMID- 9233858
TI  - Concepts in orbital reconstruction.
AB  - The diagnosis and management of orbital disease often requires the interaction of
      several specialties. The authors have reviewed the concepts in orbital
      reconstruction from an ophthalmologic, oculoplastic, otolaryngologic, and plastic
      surgical approach. Careful attention is given to the clinical examination,
      radiologic studies, surgical indications, and surgical techniques for orbital
      disease.

PMID- 9233859
TI  - Concepts in midface reconstruction.
AB  - The midface is a complex area. It is highly visible, and it participates in
      multiple critical functions of the head and neck. There is a large spectrum of
      reconstructive options that provide acceptable functional and aesthetic results.
      An understanding of the complex anatomy and physiology of the area coupled with
      adherence to basic reconstructive principles will provide consistent positive
      outcomes.

PMID- 9233860
TI  - Concepts in lip reconstruction.
AB  - Reconstruction of defects of the lip presents a significant challenge to the
      facial plastic surgeon. Both functional and aesthetic considerations exist. Each
      defect should be evaluated in terms of its location, size, and depth. Using these
      three factors, the appropriate reconstructive options can be chosen in a
      systematic fashion.

PMID- 9233861
TI  - Current concepts in oromandibular reconstruction.
AB  - Oromandibular reconstruction represents an exciting and growing area within head
      and neck reconstructive surgery. The advent and use of free tissue transfer have
      revolutionized the field. Combining these newer techniques with time-proven
      techniques presents the reconstructive surgeon with a wide array of
      reconstructive options in the oromandibular region. This article considers the
      more common and reliable methods for oromandibular reconstruction. The authors
      examine the anatomic basis of each option, highlight the literature concerning
      each technique, and make specific recommendations based on their experience.

PMID- 9233862
TI  - Prosthetic-surgical collaborations in the rehabilitation of patients with head
      and neck defects.
AB  - Resection of head and neck tumors often results in severe facial disfigurement
      and functional disabilities. Superior rehabilitation efforts rely on close
      collaboration between the resection surgeon, reconstructive surgeon, and the
      maxillofacial prosthodontist. Trauma patients are best rehabilitated surgically,
      whereas patients with head and neck tumors are best rehabilitated prosthetically
      in combination with specific surgical reconstruction procedures. This article
      describes these modifications. Surgical advancements such as microvascular free
      flaps and endosseous implants have greatly enhanced rehabilitative efforts.

PMID- 9233863
TI  - Concepts in neck reconstruction.
AB  - This article reviews the principles and techniques of reconstructing soft-tissue
      defects of the neck. The various surgical techniques, including local rotational
      flaps, tissue expansion, and free tissue transfer, are reviewed, and
      considerations in the selection of surgical techniques are discussed.

PMID- 9233864
TI  - Concepts in pharyngoesophageal reconstruction.
AB  - Pharyngoesophageal reconstruction remains a challenge in head and neck surgery.
      The anatomical defect dictates different reconstruction options possible for
      closure. This article highlights concepts in pharyngoesophageal reconstruction
      emphasizing a thought process used when choosing reconstruction options based on
      the anatomical defect. Both the partial pharyngoesophageal and total
      circumferential defects are discussed.

PMID- 9233865
TI  - Ceftriaxone compared with doxycycline for the treatment of acute disseminated
      Lyme disease.
AB  - BACKGROUND: Localized Lyme disease, manifested by erythema migrans, is usually
      treated with oral doxycycline or amoxicillin. Whether acute disseminated Borrelia
      burgdorferi infection should be treated differently from localized infection is
      unknown. METHODS: We conducted a prospective, open-label, randomized, multicenter
      study comparing parenteral ceftriaxone (2 g once daily for 14 days) with oral
      doxycycline (100 mg twice daily for 21 days) in patients with acute disseminated
      B. burgdorferi infection but without meningitis. The erythema migrans skin lesion
      was required for study entry, and disseminated disease had to be indicated by
      either multiple erythema migrans lesions or objective evidence of organ
      involvement. RESULTS: Of 140 patients enrolled, 133 had multiple erythema migrans
      lesions. Both treatments were highly effective. Rates of clinical cure at the
      last evaluation were similar among the patients treated with ceftriaxone (85
      percent) and those treated with doxycycline (88 percent); treatment was
      considered to have failed in only one patient in each group. Among patients whose
      infections were cured, 18 of 67 patients in the ceftriaxone group (27 percent)
      reported one or more residual symptoms at the last follow-up visit, as did 10 of
      71 patients in the doxycycline group (14 percent, P > or = 0.05). Mild arthralgia
      was the most common persistent symptom. Both regimens were well tolerated; only
      four patients (6 percent) in each group withdrew because of adverse events.
      CONCLUSIONS: In patients with acute disseminated Lyme disease but without
      meningitis, oral doxycycline and parenterally administered ceftriaxone were
      equally effective in preventing the late manifestations of disease.

PMID- 9233866
TI  - Improved survival in patients with locally advanced prostate cancer treated with
      radiotherapy and goserelin.
AB  - BACKGROUND: We conducted a randomized, prospective trial comparing external
      irradiation with external irradiation plus goserelin (an agonist analogue of
      gonadotropin-releasing hormone that reduces testosterone secretion) in patients
      with locally advanced prostate cancer. METHODS: From 1987 to 1995, 415 patients
      with locally advanced prostate cancer were randomly assigned to receive
      radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The
      patients had a median age of 71 years (range, 51 to 80). Patients in both groups
      received 50 Gy of radiation to the pelvis over a period of five weeks and an
      additional 20 Gy over an additional two weeks as a prostatic boost. Patients in
      the combined-treatment group received 3.6 mg of goserelin (Zoladex)
      subcutaneously every four weeks starting on the first day of irradiation and
      continuing for three years; those patients also received cyproterone acetate (150
      mg orally per day) during the first month of treatment to inhibit the transient
      rise in testosterone associated with the administration of goserelin. RESULTS:
      Data were available for analysis on 401 patients. The median follow-up was 45
      months. Kaplan-Meier estimates of overall survival at five years were 79 percent
      (95 percent confidence interval, 72 to 86 percent) in the combined-treatment
      group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the
      radiotherapy group (P=0.001). The proportion of surviving patients who were free
      of disease at five years was 85 percent (95 percent confidence interval, 78 to 92
      percent) in the combined-treatment group and 48 percent (95 percent confidence
      interval, 38 to 58 percent) in the radiotherapy group (P<0.001). CONCLUSIONS:
      Adjuvant treatment with goserelin, when started simultaneously with external
      irradiation, improves local control and survival in patients with locally
      advanced prostate cancer.

PMID- 9233867
TI  - End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest.
AB  - BACKGROUND: Survival after cardiac arrest occurring outside the hospital averages
      less than 3 percent. Unfortunately, the outcome of prolonged resuscitative
      attempts cannot be predicted. End-tidal carbon dioxide levels reflect cardiac
      output during cardiopulmonary resuscitation. We prospectively determined whether
      death could be predicted by monitoring end-tidal carbon dioxide during
      resuscitation after cardiac arrest. METHODS: We performed a prospective
      observational study in 150 consecutive victims of cardiac arrest outside the
      hospital who had electrical activity but no pulse. The patients were intubated
      and evaluated by mainstream end-tidal carbon dioxide monitoring. Our hypothesis
      was that an end-tidal carbon dioxide level of 10 mm Hg or less after 20 minutes
      of standard advanced cardiac life support would predict death. RESULTS: There was
      no difference in the mean age or initial end-tidal carbon dioxide level between
      patients who survived to hospital admission (survivors) and those who did not
      (nonsurvivors). After 20 minutes of advanced cardiac life support, end-tidal
      carbon dioxide (+/-SD) averaged 4.4+/-2.9 mm Hg in nonsurvivors and 32.8+/-7.4 mm
      Hg in survivors (P< 0.001). A 20-minute end-tidal carbon dioxide value of 10 mm
      Hg or less successfully discriminated between the 35 patients who survived to
      hospital admission and the 115 nonsurvivors. When a 20-minute end-tidal carbon
      dioxide value of 10 mm Hg or less was used as a screening test to predict death,
      the sensitivity, specificity, positive predictive value, and negative predictive
      value were all 100 percent. CONCLUSIONS: An end-tidal carbon dioxide level of 10
      mm Hg or less measured 20 minutes after the initiation of advanced cardiac life
      support accurately predicts death in patients with cardiac arrest associated with
      electrical activity but no pulse. Cardiopulmonary resuscitation may reasonably be
      terminated in such patients.

PMID- 9233868
TI  - A controlled trial of isoniazid in persons with anergy and human immunodeficiency
      virus infection who are at high risk for tuberculosis. Terry Beirn Community
      Programs for Clinical Research on AIDS.
AB  - BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and latent
      tuberculosis are at substantial risk for the development of active tuberculosis.
      As a public health measure, prophylactic treatment with isoniazid has been
      suggested for HIV-infected persons who have anergy and are in groups with a high
      prevalence of tuberculosis. METHODS: We conducted a multicenter, randomized,
      double-blind, placebo-controlled trial of six months of prophylactic isoniazid
      treatment in HIV-infected patients with anergy who have risk factors for
      tuberculosis infection. The primary end point was culture-confirmed tuberculosis.
      RESULTS: The study was conducted from November 1991 through June 1996. Over 90
      percent of the patients had two or more risk factors for tuberculosis infection,
      and nearly 75 percent of patients were from greater New York City. After a mean
      follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in
      the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48;
      95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant
      differences between the two groups with regard to death, death or the progression
      of HIV disease, or adverse events. CONCLUSIONS: Even in HIV-infected patients
      with anergy and multiple risk factors for latent tuberculosis infection, the rate
      of development of active tuberculosis is low. This finding does not support the
      use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy
      unless they have been exposed to active tuberculosis.

PMID- 9233869
TI  - Images in clinical medicine. Secondary syphilis.

PMID- 9233870
TI  - A controlled trial of an educational program to prevent low back injuries.
AB  - BACKGROUND: Low back injuries are common and costly, accounting for 15 to 25
      percent of injuries covered by workers' compensation and 30 to 40 percent of the
      payments made under that program. The high costs of injury, the lack of effective
      treatment. and the evidence that there are behavioral risk factors have led to
      widespread use of employee education programs that teach safe lifting and
      handling. The effectiveness of those programs, however, has received little
      rigorous evaluation. METHODS: We evaluated an educational program designed to
      prevent low back injury in a randomized, controlled trial involving about 4000
      postal workers. The program, similar to that in wide use in so-called back
      schools, was taught by experienced physical therapists. Work units of workers and
      supervisors were trained in a two-session back school (three hours of training),
      followed by three to four reinforcement sessions over the succeeding few years.
      Injured subjects (from both the intervention and the control groups) were
      randomized a second time to receive either training or no training after their
      return to work. RESULTS: Physical therapists trained 2534 postal workers and 134
      supervisors. Over 5.5 years of follow-up, 360 workers reported low back injuries,
      for a rate of 21.2 injuries per 1000 worker-years of risk. The median time off
      from work per injury was 14 days (range, 0 to 1717); the median cost was $204
      (range, zero to $190,380). After their return to work, 75 workers were injured
      again. Our comparison of the intervention and control groups found that the
      education program did not reduce the rate of low back injury, the median cost per
      injury, the time off from work per injury, the rate of related musculoskeletal
      injuries, or the rate of repeated injury after return to work; only the subjects'
      knowledge of safe behavior was increased by the training. CONCLUSIONS: A large
      scale, randomized, controlled trial of an educational program to prevent work
      associated low back injury found no long-term benefits associated with training.

PMID- 9233871
TI  - Managing managed care's tarnished image.

PMID- 9233872
TI  - Prostate cancer--the therapeutic challenge of locally advanced disease.

PMID- 9233873
TI  - Workers with disabling back pain.

PMID- 9233874
TI  - Cost effectiveness of oral as compared with intravenous antibiotic therapy for
      patients with early Lyme disease or Lyme arthritis.

PMID- 9233876
TI  - Gastric involvement in Waldenstrom macroglobulinemia: CT findings.
AB  - Waldenstrom macroglobulinemia is a plasma cell dyscrasia that rarely presents
      with gastrointestinal involvement. We report a case of gastric involvement of
      Waldenstrom macroglobulinemia detected by CT.

PMID- 9233875
TI  - CT of Nissen's fundoplication.
AB  - The aim of this work is to describe the computed tomographic (CT) anatomy in
      patients who underwent Nissen's fundoplication. Forty patients (mean age = 61
      years) with peptic esophagitis (nine cases), refractory gastroesophageal reflux
      (11 cases), and hiatal hernia (20 cases) were studied. Examinations were
      performed by third-generation CT equipment, with patients in the prone position
      after the ingestion of gastrovison and barium paste. In 34 patients, the
      examination demonstrated anatomical variations related to surgery, that is, the
      presence of a soft tissue mass at the level of the distal third of the esophagus.
      In four patients, a functional incompetence of the fundoplication (three cases)
      and a recurrent hiatal hernia (one case) were demonstrated. Our results suggest a
      possible application for CT study in postoperative follow up of patients who
      undergo Nissen's fundoplication, complementary to endoscopy and functional exams.

PMID- 9233877
TI  - CT appearance of direct leukemic invasion of bowel.
AB  - Although leukemic invasion of bowel is frequently seen on pathologic examination,
      it has rarely been described in the imaging literature. Previous radiographic
      reports have relied mostly on non-cross-sectional imaging techniques such as
      barium enema and have detected abnormalities only in the most advanced stages of
      disease when prognosis is uniformly poor. We describe a case of direct leukemic
      invasion seen on computed tomography which may offer the advantage of earlier
      detection and more favorable prognosis.

PMID- 9233878
TI  - Small bowel obstruction in the pediatric patient: CT evaluation.
AB  - BACKGROUND: Little has been written about the use of computed tomography (CT) in
      the evaluation of small bowel obstruction (SBO) in children. The purpose of this
      study is to review the CT findings of SBO in a pediatric series and to increase
      awareness of CT as potential problem-solving tool for SBO in children. METHODS:
      The medical, surgical, radiographic, and CT scan records of 20 consecutive
      children with surgically proven SBO were retrospectively reviewed. Duodenal and
      neonatal obstruction was excluded. CT scans were evaluated for small and large
      bowel caliber, bowel wall thickening, the appearance of the mesentery,
      extraluminal abnormalities, and the ability to detect the cause of obstruction.
      RESULTS: Causes of obstruction included adhesions (nine), small bowel
      intussusception (four), abscess (two), segmental volvulus (two), Crohn disease
      (one), focal stricture (one), and internal hernia (one). Small bowel dilatation
      was present in 19/20 children. Small bowel caliber transition was noted in 17/19
      children. Two children with no small bowel caliber transition had a collapsed
      colon. The colon appeared normal in caliber in nine children, collapsed in nine,
      and filled with stool proximally and collapsed distally in two. Small bowel
      thickening was present in six children and mesenteric venous engorgement in
      three. Specific causes of obstruction were identified on CT in nine children
      (45%) and could be correctly predicted in seven of nine children with adhesions.
      In four children, the causes were either not evident or alternate diagnoses could
      be made. CONCLUSION: CT can be a useful adjunct in evaluating the presence or
      causes of SBO in children.

PMID- 9233879
TI  - Small bowel obstruction due to phytobezoar: CT diagnosis.
AB  - We report two cases of small bowel obstruction (SBO) due to phytobezoar
      impaction. In both cases, computed tomography (CT) demonstrated a well-defined,
      ovoid intraluminal mass with mottled gas pattern within the dilated small bowel
      at the site of obstruction and an abruptly collapsed lumen beyond the lesion.
      Recognition of these CT findings allows specific preoperative diagnosis of SBO
      owing to this uncommon lesion.

PMID- 9233880
TI  - Cholecystojejunostomy varices demonstrated by enteroclysis.
AB  - Varices in unusual sites constitute a minor but significant cause of
      gastrointestinal bleeding in patients with liver disease. We report a case of
      varices across the anastomotic line between the jejunum and gallbladder after
      cholecystojejunostomy. Although such varices have been demonstrated by
      angiography, to our knowledge they have never been demonstrated by small bowel
      enema (enteroclysis). We report a case and describe the findings on enteroclysis.

PMID- 9233881
TI  - CT of the mesenteric vascular anatomy.
AB  - BACKGROUND: To evaluate the appearance of the arrangement of the superior
      mesenteric artery (SMA) and superior mesenteric vein (SMV) on computed tomography
      (CT) in normal patients and in patients with abdominal masses. METHODS: One
      hundred seventy-seven consecutive abdominal CT examinations of 143 adults and two
      children were reviewed. The relationship of the SMV to the SMA was recorded at
      four locations: the beginning of the mesenteric vessels and levels 3 cm, 6 cm,
      and 9 cm caudad to the beginning. The relationship of the SMV to the SMA was
      divided into four quadrants in relation to the SMA: I, ventral right or directly
      ventral; II, dorsal right or directly right; III, dorsal left or directly dorsal;
      and IV, ventral left or directly left. RESULTS: In the beginning of the SMV-SMA
      complex and levels 3 cm, 6 cm, and 9 cm caudal to the beginning, the SMV was
      located in quadrant I in 146, 84, 69, and 43 examinations, in quadrant II in 31,
      93, 71, and 27 examinations, in quadrant III in zero, zero, five, and three
      examinations, and in quadrant IV in zero, zero, nine, and 15 examinations,
      respectively. The cases with SMV inversion had neither malrotation nor adjacent
      tumor compression. All the cases with an adjacent tumor-induced compression of
      the SMV-SMA complex had a normal SMV-SMA relationship. CONCLUSION: In the first 3
      cm, the SMV is always to the right of the SMA. Caudal to the level of 6 cm, the
      SMV may be located to the left of the SMA without evidence of malrotation. A
      midgut nonrotation is more likely to be present when a proximal SMV inversion is
      coexistent with a rightward direction of the proximal jejunal vessels. A
      hypothetical depiction of the step-by-step change of the SMV-SMA relationship
      during embryologic development may explain the arrangement patterns of the
      mesenteric vessels in normal rotation and midgut nonrotation.

PMID- 9233882
TI  - Superior mesenteric artery Doppler waveform changes in response to inflammation
      of the ileocecal region.
AB  - In the present study, we determined how Doppler waveforms of the superior
      mesenteric artery (SMA) are affected by inflammatory processes in the ileocecal
      region. Twenty-two patients (aged 20-69 years) with ileocecal region inflammation
      (ICRI) were examined with duplex Doppler Ultrasonography to establish whether any
      significant changes were present in the mean blood flow parameters of peak
      systolic velocity (PSV), end-diastolic velocity (EDV), resistive index,
      pulsatility index, blood flow volume, and diameter of the SMA. The findings were
      compared with those of 22 volunteer controls. Mean blood flow volume in the SMA
      in patients with ICRI (1.128 +/- 0. 43 L/min) was significantly greater (p <
      0.001) than that in the control group (0.643 +/- 0.19 L/min). The mean PSV (1.87
      +/- 0.44 m/s) and the mean EDV (0.31 +/- 0.18 m/s) were also significantly (p <
      0.01) higher than those of the means in healthy subjects (mean PSV = 1.44 +/-
      0.26 m/s and mean EDV = 0.20 +/- 0.05 m/s). ICRI, regardless of cause, increases
      both the flow velocities in the SMA and the flow volume to the SMA territory.

PMID- 9233883
TI  - Superior mesenteric artery Doppler waveform changes in response to inflammation
      of the ileocecal region.

PMID- 9233884
TI  - Endoscopic pancreatic intervention.

PMID- 9233885
TI  - Fatty infiltration of the liver distal to a metastatic liver tumor.
AB  - We report a case of focal fatty infiltration of the liver parenchyma adjacent to
      a metastatic liver tumor from an islet cell tumor. The decreased portal flow by
      the tumor and insulin produced by the tumor cells might be causes of focal fatty
      infiltration.

PMID- 9233886
TI  - Primary Budd-Chiari syndrome due to complex venous anomalies.
AB  - A 35-year-old woman with clinical features of Budd-Chiari syndrome is presented.
      Abdominal ultrasonography, computed tomography, and venography disclosed that the
      venous congestion in this patient resulted from complex venous anomalies
      including azygos-hemiazygos continuation, absent superior hepatic veins, and
      retroaortic transposition of the left renal vein.

PMID- 9233887
TI  - Aberrant gastric venous drainage into the medial segment: demonstration by color
      Doppler sonography.
AB  - BACKGROUND: Aberrant gastric venous drainage (AGVD) into the posterior edge of
      the medial segment of the liver (segment IV) is the main cause of pseudolesion on
      computed tomography (CT) during arterial portography. We estimated the prevalence
      of AGVD into the medial segment of the liver with color and power Doppler
      ultrasound (US). METHODS: Screening gray-scale and color Doppler and power
      Doppler US were performed in 100 consecutive patients. AGVD was defined as a
      venous structure that ascended parallel to the main portal vein and drained
      independently into segment IV. RESULTS: AGVDs were observed in eight of 100
      patients (8%) with color and power Doppler US. Power Doppler US depicted these
      veins more clearly than did color Doppler US. Gray-scale US did not show any
      AGVDs. Two of eight patients with AGVDs detected by color Doppler US underwent
      celiac arteriography and CT during arterial portography (CTAP). In these two
      patients, celiac arteriography directly demonstrated AGVDs draining into segment
      IV, which revealed nontumorous perfusion defects (pseudolesions) on CTAP.
      CONCLUSION: Color and power Doppler US are useful imaging methods for
      demonstrating AGVDs.

PMID- 9233888
TI  - Portal vein absence and nodular regenerative hyperplasia of the liver with giant
      inferior mesenteric vein.
AB  - We present a patient with nodular regenerative hyperplasia of the liver (NRH) and
      portal vein absence studied with CT, MR imaging, and MR angiography. The most
      striking feature was exuberant hemorrhoids due to a giant hepatofugal inferior
      mesenteric vein. A relationship between unbalanced portal blood flow and nodular
      regenerative transformation of the liver is suggested in this patient.

PMID- 9233889
TI  - The normal retrograde cholangiogram: a definition of normal caliber.
AB  - PURPOSE: To evaluate normal retrograde cholangiograms to determine a normal range
      of ductal calibers and identify its variation with age. MATERIALS AND METHODS:
      The retrograde cholangiograms of 136 patients (age range: 17-84 years; mean age
      49.8 years +/- 17.3 [standard deviation]) with clinical follow-up and subsequent
      studies suggesting normal biliary trees were evaluated. Patients with previous
      cholecystectomy, choledocholithiasis, or pancreatitis were excluded. Common bile
      duct (CBD) and common hepatic duct (CHD) sizes were measured. RESULTS:
      Measurements uncorrected for radiographic magnification of CBD revealed a mean of
      8.5 mm +/- 2.7 mm [standard deviation] and CHD had a mean of 8.1 mm +/- 2.6 mm.
      There was an increase in CBD caliber by 0.5 mm per decade of increasing age (p <
      0.001) and an increase in CHD caliber by 0.35 mm per decade of age (p < 0.01).
      CONCLUSION: The range of normal cholangiographic bile duct caliber is wide and a
      CBD caliber of 13.9 mm occurs at the top of this range (mean plus two standard
      deviations). There is a small but statistically significant trend of ductal
      dilatation with advancing age.

PMID- 9233890
TI  - Colovenous fistula complicating diverticulitis: CT and radiographic findings.
AB  - We report a case of colovenous fistula to the inferior mesenteric vein
      complicating diverticulitis and mimicking coloureteral fistula. This is the
      second reported case of venous intravasation of barium complicating
      diverticulitis that mimicks coloureteral fistula. Radiographic features and
      characteristics differentiating these two entities are presented.

PMID- 9233891
TI  - Coexistent cystic teratoma of the omentum and ovary: report of two cases.
AB  - Benign cystic teratoma (dermoid cyst) of the omentum is a rare tumor, while
      ovarian cystic teratoma is one of the most common ovarian neoplasms. Seven cases
      of cystic teratoma of the omentum have been reported in association with an
      ovarian teratoma. We report two cases associated with an ovarian teratoma, which
      shows unusual dense rim calcification of the cystic wall.

PMID- 9233892
TI  - Abdominal visceral calcification in primary amyloidosis: CT findings.
AB  - The computed tomographic (CT) findings of extensive visceral calcification
      involving both the liver and spleen in a patient with primary amyloidosis are
      presented. Although the CT imaging appearances of amyloidosis are often
      nonspecific, visceral calcification represents an important diagnostic clue for
      differentiating this entity from other infiltrative parenchymal diseases.

PMID- 9233893
TI  - Infiltrative subcutaneous metastases from ovarian carcinoma after paracentesis:
      CT findings.
AB  - Implantation subcutaneous metastases from ovarian cancer are an uncommon event in
      surgery, and diagnostic procedures such as laparoscopy, fine-needle biopsy, and
      intraperitoneal catheter access are usually used. Findings of tumor implantations
      are rarely reported with diagnostic imaging techniques. In this case, an
      infiltrative subcutaneous metastasis appeared on computed tomography 4 months
      after paracentesis in a patient with untreated ovarian cancer. Differential
      diagnostic problems are discussed.

PMID- 9233894
TI  - MR intervention in the pelvis: an overview and first experiences in MR-guided
      biopsy in nodal metastases in urinary bladder cancer.

PMID- 9233895
TI  - Rapid T2-weighted MR imaging of uterine leiomyoma and adenomyosis.
AB  - BACKGROUND: To compare three rapid T2-weighted pulse sequences with high
      resolution turbo spin-echo (SE) magnetic resonance (MR) imaging for the diagnosis
      of leiomyoma and adenomyosis. METHODS: Eighteen patients referred for evaluation
      of suspected leiomyoma or adenomyosis underwent imaging at 1.5 T with a phased
      array multicoil. Non-breath-hold, fat-saturated sagittal images of 4-7 mm, with
      equivalent voxel size, were obtained through the pelvis with the following three
      rapid pulse sequences: segmented, half-Fourier single shot turbo SE (HASTE),
      turboGRASE (TGSE) and turbo SE MR images. Mean acquisition times were 17 s
      (HASTE), 37 s (TGSE), and 42 s (turbo SE). These images were compared, in a
      blinded fashion, to high resolution turbo SE MR images, which are considered the
      "standard" for pelvic MRI. RESULTS: The three rapid pulse sequences, HASTE, TGSE
      and turbo SE, provided equivalent diagnostic information when compared with high
      resolution turbo SE MR images. There was no significant difference in image
      quality, detection and localization of leiomyoma or in diagnosis of adenomyosis
      among the three rapid sequences. HASTE imaging demonstrated the least ghosting.
      CONCLUSION: Diagnostic T2-weighted images of benign uterine pathology may be
      obtained in as little as 17 s.

PMID- 9233896
TI  - Ovarian fibroma: findings by contrast-enhanced MRI.
AB  - Ovarian fibromas are solid neoplasms that are difficult to differentiate
      radiologically from uterine leiomyomas. In this report, we describe the contrast
      enhanced magnetic resonance imaging features of a 13-cm-diameter solid pelvic
      mass that allowed us to make the prospective diagnosis of ovarian fibroma.

PMID- 9233897
TI  - The query corner. Narrowing of the common hepatic duct found on ERCP.

PMID- 9233898
TI  - The query corner. Cholangiographic distinction between common bile duct calculi
      and air bubbles.

PMID- 9233899
TI  - Endocrine testicular function in HIV-infected outpatients.
AB  - We investigated endocrine testicular function in 100 HIV-infected men who were
      grouped according to the CDC criteria. Progression of the disease was associated
      with a 27% decrease in plasma oestradiol, which was the only parameter that was
      weakly correlated with CD4 cell count (r = 0.312, p <0.05). Individual data
      showed a decreased plasma concentration of total and free testosterone in 35% and
      26% of the subjects, respectively, but we could not demonstrate an increased
      frequency of hypogonadism going along with a progression of the stage of disease.
      There was no significant correlation between androgen, SHBG or FSH levels and
      duration of HIV-infection, BMI or CD4 cell count. Hypergonadotropic hypogonadism
      was associated with an euthyroid sick state in a 15% subgroup of patients
      reporting a decrease in libido. Plasma T3 was significantly correlated with
      testosterone (r = 0.419, p <0.01) and mean plasma T3 was significantly decreased
      in 8 subjects suffering from erectile impotence. Thus, hypogonadism occurs
      frequently in HIV-infected outpatients. Like euthyroid sickness it does not seem
      to be a predictor for progression of the disease but an indicator of actual state
      of health.

PMID- 9233900
TI  - Serum levels of basic fibroblast growth factor in acute myocardial infarction.
AB  - As it has been reported that basic fibroblast growth factor (bFGF) is a
      circulating peptide and bFGF gene expression is increased after myocardial
      ischemia, this study was designed to investigate the serum levels of bFGF in
      patients with acute myocardial infarction (AMI). Using a bFGF enzyme-linked
      immunoassay, bFGF levels were determined in venous blood of 15 patients with AMI
      on admission, at 10 days, and 30 days after infarction, and of 15 age-matched
      healthy volunteers who were used as controls. bFGF serum levels on admission were
      similar to normal values (7.48 +/- 2.3 vs 8.14 +/- 2.9 pg/ml). However, they
      significantly increased (16.82 +/- 3.4 pg/ml; p <0.05) 10 days after the onset of
      AMI, and at 30 days they returned to baseline (7.07 +/- 2.9 pg/ml). The increased
      bFGF levels at the second week post AMI suggest that bFGF plays an important role
      in mediating the development of coronary collateral circulation after myocardial
      ischemia in humans.

PMID- 9233901
TI  - Regulation of the angiotensin AT1 receptor expression by hypercholesterolemia.
AB  - The AT1 receptor mediates most of the biological effects of angiotensin II and
      has therefore been implicated in the pathogenesis of hypertension as well as
      arteriosclerosis. Hypercholesterolemia is a prominent risk factor for the
      development of these cardiovascular diseases. Since experimental results from
      hyperlipidemic animal models suggested an interaction of the renin-angiotensin
      system and hypercholesterolemia, the effects of low-density lipoprotein (LDL) and
      hypercholesterolemia has recently been investigated in vitro and in vivo. LDL
      causes in cultured vascular smooth muscle cells an up-regulation of AT1 receptor
      gene expression which is followed by an enhanced functional response upon
      stimulation with angiotensin II. This effect is also evident in vivo, as assessed
      in hypercholesterolemic rabbits. The vascular AT1 receptor expression is
      increased approximately twofold in hypercholesterolemic rabbits in comparison to
      normocholesterolemic animals. This leads ultimately to an enhanced angiotensin II
      induced vasoconstriction. Thus, hypercholesterolemia and elevated concentrations
      of LDL enhance AT1 receptor expression in the vasculature causing an enhanced
      biological effectiveness of the renin-angiotensin system. This interaction may
      explain that blockade of the renin-angiotensin system attenuates the progress of
      arteriosclerosis in the hypercholesterolemic organismen and indicates a
      pathophysiologically important role for the lipid-induced AT1 receptor up
      regulation.

PMID- 9233902
TI  - Vaccine tolerance in steroid substituted patients with congenital adrenal
      hyperplasia.
AB  - The tolerance and side effects of vaccinations were determined in patients with
      congenital adrenal hyperplasia (CAH) who receive physiological corticosteroid
      substitution. In a retrospective approach, questionnaires about the frequencies
      of vaccinations and observed side effects were sent to CAH patients, and medical
      records were reviewed. We received 82 questionnaires from 63 patients with CAH
      and salt-losing and 19 patients without salt-losing. Patients age ranged from 2
      40 years. No statistical differences were found for vaccination frequencies
      between patients with or without salt-losing. CAH patients had received complete
      vaccinations against diphtheria, tetanus and poliomyelitis in 79%, 85% and 78%,
      respectively, whereas pertussis vaccination was complete in only 23%. Live
      vaccination against measles, mumps and rubella was performed in 63%, 50% and 38%.
      Side effects of vaccination were indicated in 5 out of 82 questionnaires who all
      belonged to CAH patients with salt-losing. Transient side effects were an
      anaphylactic reaction, probably to tetanus immunoglobulin, in 1 case, and fever
      and convulsions after diphtheria, pertussis and tetanus (DPT) vaccine in 2 cases.
      In 2 further patients putative complications were noted. Encephalitis with
      permanent disabilities was observed after the third DPT vaccination, but a
      causative relation could not be established. In another boy, encephalopathy
      noticed after measles vaccination was induced by previous toxicosis. Although
      encephalopathy was described in 2 patients after vaccinations, no vaccination
      damage could be proven in our retrospective study. As expected, an increased
      vaccination risk in CAH patients was not demonstrated.

PMID- 9233903
TI  - Effects of various modes of androgen substitution therapy on erythropoiesis.
AB  - In order to investigate differential effects of androgens on erythropoiesis, 55
      men with clincally and biochemical confirmed hypogonadism were randomly assigned
      to 4 groups receiving different forms of androgen substitution: Mesterolone (MES)
      100 mg/d, testosterone undecanoate (TU) 160 mg/d, testosterone enanthate (TE) 250
      mg i.m./21 days or 1200 mg crystalline testosterone (TPEL) subcutaneously
      implanted at study begin. Previous testosterone medication had been suspended at
      least 3 months prior to study begin. Testosterone (T), dihydrotestosterone (DHT),
      hemoglobin (HB) and hematocrit (HC) were assessed before, during and after
      substitution of androgens. MES did not increase serum T and TU raised average T
      levels during substitution to 5.7 +/- 0.3 nmol/l, thereby doubling baseline
      concentrations. TE resulted in a 6fold increase of baseline T yielding 13.5 +/-
      0.7 nmol/l and TPEL increased serum T 8.5fold to 23.2 +/- 1.1 nmol/l. Average DHT
      levels during substitution were 4.3 +/- 0.2 (MES), 3.3 +/- 0.2 (TU), 4.0 +/- 0.4
      (TE) and 5.5 +/- 0.4 (TPEL) nmol/l. The groups receiving TPEL, TU or TE showed a
      significant rise of HB and HC compared to baseline, whereas in the MES group
      these parameters did not change significantly. MES increased HB by 5.6 +/- 1.8
      g/l, TU by 12.7 +/- 2.8 g/l, TE by 21.1 +/- 2.6 g/l and TPEL by 21.7 +/- 4.0 g/l.
      HC was raised by 1.8 +/- 0. 4% in the MES group, 3.9 +/- 1.1% in the TU group and
      6.4 +/- 0.9% and 6.5 +/- 1.6% in the TE and TPEL groups, respectively. Except for
      1 subject in the TPEL group, the HB and HC stayed within the normal limits. We
      conclude that, T, but not DHT, stimulates erythropoiesis in a dose dependent
      manner. T levels within the low normal range for men are required for maximal
      stimulation of erythropoiesis.

PMID- 9233904
TI  - Identification of Doppler microembolic signals with a bigate probe in patients
      with prosthetic heart valves.
AB  - BACKGROUND AND PURPOSE: The applicability of a bigate probe, simultaneously
      harvesting two spatially separated vessel segments, in the identification of
      Doppler microembolic signals (MES) was evaluated. METHODS: One hundred and ninety
      seven patients with artificial heart valves were bilaterally monitored over two
      segments of each middle cerebral artery, with a minimal distance of 5 mm between
      them, using 2 MHz probes. Time delay in the appearance of high intensity
      transients between the two segments was calculated off-line, using dedicated
      software, integrated in the Doppler device. RESULTS: Bigate monitoring was
      feasible in 96% of patients. MES prevalence and counts were 37% and 26 (18-44)
      respectively. All but 8.8% of the 2932 MES signals recorded appeared in both
      Doppler channels, with a time delay of 4.4 (4.2-4.7) msec (range between 0 and 34
      msec). Time delay in 97% of artifact signals was under 1 msec. Application of 1
      msec as low and 20 msec as high cut-off point between MES and artifacts resulted
      in the correct identification of 97% of artifacts and 89.6% of MES. CONCLUSIONS:
      The multigate approach is a reliable method for identification of Doppler
      microembolic signals in patients with prosthetic heart valves. The value of this
      technique in other patient groups remains to be evaluated.

PMID- 9233905
TI  - Kinins are implicated of the hypotensive effect of acidic fibroblast growth
      factor.
AB  - Acidic fibroblast growth factor causes an acute and transient nitric oxide
      dependent hypotensive effect in experimental animals. However, this response is
      not found, or is very small, in vitro. We hypothesized that plasma mediators,
      such as kinins, are involved in aFGF-induced hypotension. We studied the
      hypotensive effect of intravenous aFGF (1 microg) in control Wistar rats, and
      compared this response to that in Wistar rats treated with a bradykinin receptor
      antagonist Na-adamantaneacetyl-D-Arg-(Hyp3,Thi5,8,D-Phe7]-brad yki nin), in
      kininogen-deficient Brown-Norway-Katholiek (BNK) rats, and in rats depleted of
      kininogen after repeated treatment with ellagic acid. FGF was administered in the
      jugular vein and mean arterial pressure was measured through a femoral artery
      catheter. Following treatment with the bradykinin receptor antagonist, the
      hypotensive effect of aFGF was reduced 38% with 58 microg of antagonist and by
      60% with the 420 microg dose (9 +/- 1 vs 22 +/- 3mm Hg, p<0.01). Mean blood
      pressure decrease was 12 +/- 1 in BNK rats (p<0.01, vs control) and 10 +/- 2 mm
      Hg in kininogen-depleted ellagic acid-treated rats (p<0.05, vs control). These
      findings implicate kinins as necessary mediators for the hypotensive effect of
      aFGF in vivo. A full hypotensive effect of aFGF requires sufficient amounts of
      kininogens, the precursor molecules of kinins, as well as bradykinin receptors.

PMID- 9233906
TI  - Protein kinase C activation after cellular adhesion on fibronectin: partial
      suppression after inhibition of protein isoprenylation.
AB  - The cellular events following interaction between matrix proteins and cells are
      important requisites for physiological mechanisms as well as the progress of a
      number of diseases. Cellular adhesion to fibronectin, an important component of
      the extracellular matrix has been demonstrated to be associated with
      translocation of protein kinase C (PKC) by an integrin-dependent pathway. For
      this process G-proteins may play an important role as coupling proteins. Membrane
      association and activity of G-proteins has been shown to be regulated by
      isoprenylation. We therefore studied whether fibronectin mediated adhesion
      resulted in PKC translocation and if isoprenylation of cellular proteins may play
      a role for this integrin-dependent pathway of PKC activation. Chinese hamster
      ovary (CHO) cells were pretreated with either the Hydroxy-methylglutaryl(HMG)-CoA
      reductase inhibitor lovastatin or prenylation inhibitor limonene. For the
      stimulation by extracellular matrices, CHO cells were plated on tissue culture
      dishes coated with fibronectin or bovine serum albumin and PKC activity was
      determined. To investigate direct effects of inhibition of isoprenylation on
      cytoskeletal organization, phalloidin-stained stress fibers were characterized
      after adhesion on different matrices. CHO cells seeded on fibronectin displayed
      over twice the PKC translocation to the particulate fraction in comparison to
      that measured in cells on albumin. Pretreatment of CHO cells with lovastatin or
      limonene resulted in partial suppression of PKC activation after cell-seeding on
      the specific matrix fibronectin. Changed PKC distribution was not due to a
      disorganization of the actin skeleton. These data show that inhibition of
      isoprenylation of cellular proteins, possibly small Guanosine triphosphate(GTP)
      binding proteins, alters only the integrin-mediated PKC distribution but does not
      greatly influence constitutive PKC distribution.

PMID- 9233907
TI  - Ophthalmoplegia plus: clinical relevance of magnetic resonance tomogaphy
      findings.
AB  - The diagnostic value of magnetic resonance imaging (MRI) in patients with
      ophthalmoplegia plus was evaluated. Twenty patients in whom the diagnosis of
      opthalmoplegia plus was clinically and histochemically established underwent
      magnetic resonance and electrophysiological studies. Three types of
      neuroradiological abnormalities were found in 14 patients: (1) cerebral and/or
      cerebellar atrophy (n = 11), (2) hyperintense lesions of the white matter or
      pyramidal tract (n = 2), or (3) both (n = 1). The diagnostic yield of MRI was
      low, since clinically or electrophysiologically manifest lesions were missed in 4
      cases and the pathological findings were non-specific, since they are seen in
      several demyelinating diseases. Our results suggest that MRI provides no
      additional information in patients with manifest ophthalmoplegia plus. We
      conclude that clinical presentation and evidence of ragged red fibers are the
      cornerstones in diagnosis of ophthalmoplegia plus.

PMID- 9233908
TI  - Plasma endothelin-1 level in patients with renovascular hypertension - does the
      kidney with stenosis of the renal artery upregulate production of endthelin-1?
AB  - PROBLEM: To examine the value of plasma endothelin-1 (ET-1), we measured the
      level of plasma ET-1 activity of peripheral venous blood and selective renal
      venous blood in renovascular hypertension patients, and compared that activity
      with corresponding renin activity and split renal function. METHODS: ET-1 level,
      renin activity in selective renal venous blood and peripheral venous blood, and
      99mTc-dimercaptosuccinic acid renal uptake as a split renal function test were
      measured in 11 patients (mean 42.1 years old) with renovascular hypertension
      (RVH) and 6 patients with both renal cell cancer (RCC) and essential
      hypertension. RESULTS: 1. In patients with RVH, resting peripheral venous plasma
      ET-1 ranged from 0.6 to 8.1 (mean 4.07) pg/ml and was higher than the normal
      level (p <0.01). However, the renal vein ET-1 ratio was nor correlated with the
      renal vein renin ratio. 2. In patients with RCC, resting peripheral venous plasma
      ET-1 was not different from the normal level. There was no step-up of plasma ET
      1, or renin among renal veins, or the proximal and distal parts of the interior
      vena cava. 3. Both renal vein renin ratio and renal vein ET-1 ratios were
      inversely correlated with t99mTC-dimercaptosuccinic acid renal uptake as a split
      renal function examination in patients with RVH. 4. The peripheral plasma ET-1
      level was correlated with the degree of stenosis of the renal artery in patients
      with RVH of a unilateral lesion, but not bilateral lesions. CONCLUSION: These
      results suggest that ET-1 may take part in the hypertensive mechanisms of RVH in
      addition to the renin-angiotensin system, but its significance in RVH still
      remains to be examined.

PMID- 9233972
TI  - Babywalker-related injuries continue despite warning labels and public education.
AB  - OBJECTIVE: To describe the epidemiology of babywalker-related injuries to
      children treated in a pediatric emergency department despite current prevention
      efforts, and to investigate the beliefs of parents regarding babywalker use.
      DESIGN: A descriptive study of a consecutive series of patients. SETTING: The
      emergency department of a large, academic children's hospital. PARTICIPANTS:
      Children treated for babywalker-related injuries during the 3-year period of
      March 1993 through February 1996. RESULTS: There were 271 children treated for
      babywalker-related injuries. The mean age was 9.2 months, and 62% of patients
      were boys. Ninety-six percent of children were injured when they fell down stairs
      in their babywalker. The number of stairs that a child fell down was
      significantly associated with skull fracture and admission to the hospital, and a
      fall down more than 10 stairs had a relative risk (RR) of skull fracture = 3.28
      (95% confidence interval, 1.35 < RR < 7.98). There were 159 children with
      contusions/abrasions (58.6%), 35 concussions/head injuries (12. 9%), 33
      lacerations (12.2%), 26 skull fractures (9.6%), 9 epistaxis (3.3%), 4 nonskull
      fractures (1.5%), 4 avulsed teeth (1.5%), and 1 burn (0.4%). Three of the skull
      fractures were depressed, and three also had accompanying intracranial
      hemorrhage. Ten patients (3.7%) were admitted to the hospital, and all had skull
      fractures resulting from falls down stairs. Supervision was present in 78% of
      cases, including supervision by an adult in 69% of cases. Forty-five percent of
      families kept the walker, and 32% used the walker again for the study patient or
      another child after the injury episode. Fifty-nine percent of parents
      acknowledged that they were aware of the potential dangers of babywalkers before
      the injury event. Fifty-six percent of parents favored a national ban on the sale
      of walkers, and 20% were opposed. CONCLUSION: Despite the currently used
      prevention strategies, including adult supervision, warning labels, care giver
      education programs, and stairway gates, serious injuries associated with
      babywalkers continue to occur to young children. The US Consumer Product Safety
      Commission should promulgate a rule, similar to the voluntary standard adopted in
      Canada, regarding design requirements for babywalkers that will prevent their
      passage through household doorways at the head of stairs. The manufacture and
      sale of mobile babywalkers that do not meet this new standard should be banned in
      the US. A recall or trade-in campaign should be conducted nationally to decrease
      the number of existing babywalkers.

PMID- 9233973
TI  - Escalator-related injuries in children.
AB  - OBJECTIVE: Escalator-related trauma is uncommon but can cause significant injury.
      This study reviewed escalator-related injuries in children to determine risk
      factors, types of injuries, medical interventions, and long-term outcomes. DESIGN
      AND SETTING: Retrospective clinical patient series, Municipal Hospital Pediatric
      Emergency Service. Participants. All children less than 18 years of age who
      presented to the Pediatric Emergency Service with an escalator-related injury
      from August 1990 through February 1995. METHODS: We reviewed the chart and
      interviewed the parent of each child by telephone. We collected the following
      information: age, gender, child's supervision and activity while on the
      escalator, escalator location, direction of motion, presence of escalator
      defects, nature and extent of injury, medical interventions, and outcome.
      RESULTS: Twenty-six children had escalator-related injuries. The average age was
      6 years (range, 2-16). Thirteen children (50%) were 2 to 4 years old. There were
      15 (57%) boys. Eighteen children (69%) were accompanied by an adult. All children
      7 years and younger were accompanied by an adult; however, 50% were not holding
      the hand of their guardian. Eight children (31%) were injured while riding
      improperly, ie, walking, running, playing, or sitting on the escalator, and among
      these, all who were standing fell down before the injury. Six (23%) children were
      injured while stepping off the escalator. Of 9 children less than 4 years old, 7
      (78%) were riding the escalator properly. Of 9 children 4 years or older, only 3
      (33%) were riding properly. Circumstances of injury included falling down with
      subsequent blunt trauma, falling down with subsequent entrapment of an extremity,
      and entrapment of an extremity not related to falling down. Locations of
      entrapment were between two steps, between a step and the side-rail, and between
      the last step and the comb plate. Twenty-one (81%) injuries occurred in rail or
      subway stations. Eight escalators were reported to have functional or structural
      problems. Seventeen (65%) children sustained lower extremity injuries and 8 (31%)
      sustained upper extremity injuries. Injuries included lacerations, avulsions and
      degloving injuries of the extremities, tendon and nerve lacerations, and digit
      fractures and amputations. Thirteen (50%) children were admitted to the hospital
      for operative management; the average length of hospitalization was 13 days
      (range 1-29). Four children (15%) suffered significant functional loss, and 12
      (46%) sustained permanent cosmetic deformities. CONCLUSION: Children are at risk
      for sustaining severe injuries on escalators. Young age, inadequate adult
      supervision, improper activity while riding on the escalator, and escalator
      related mechanical problems all increase the risk of injury. Public and parent
      education directed toward escalator safety issues may help to reduce escalator
      related injuries in children.

PMID- 9233974
TI  - Beyond dorsal penile nerve block: a more humane circumcision.
AB  - OBJECTIVE: To explore techniques that can be utilized in addition to the dorsal
      penile nerve block (DPNB) to further reduce the neonate's stress and pain from
      routine circumcision, and thus make the procedure more humane. SETTING: Level 1
      nursery at a community hospital. SUBJECTS: Eighty healthy, term, newborn male
      infants scheduled for routine neonatal circumcision. STUDY DESIGN: Prospective
      and randomized; double blind and placebo controlled for the study solutions.
      METHODS: Four statistically similar groups of 20 were studied. The control group
      included infants circumcised using: a) a rigid plastic restraint board; b)
      standard DPNB; and c) a pacifier dipped in water to comfort the infant. Each
      study group differed from the controls in one variable including: 1) using a
      specially designed, physiologic circumcision restraint chair; 2) pH buffering of
      lidocaine hydrochloride used for DPNB; and 3) offering a pacifier dipped in a 24%
      sucrose solution during the DPNB and circumcision. Behavioral observations were
      recorded and compared for each group starting before the injection of lidocaine
      hydrochloride and continuing through the completion of the circumcision. Plasma
      for cortisol levels were collected 30 minutes after the circumcision. RESULTS:
      Neonates circumcised on the new restraint chair showed a significant decrease in
      distress scores (>50%) compared with the control group on the rigid molded
      plastic restraint. The pacifier dipped in sucrose had a distress-reducing effect
      during both the post-DPNB injection and circumcision periods. The infants who
      were injected with the buffered lidocaine showed no differences in distress from
      the controls. The plasma cortisol levels were not significantly affected by any
      additional technique and were comparable to the levels previously reported.
      CONCLUSIONS: When neonatal circumcisions are performed routinely, they should be
      done as humanely as possible. This study demonstrates that, when used in
      conjunction with DPNB, a pacifier dipped in 24% sucrose and a more comfortable,
      padded, and physiologic restraint can be useful in decreasing distress and pain.

PMID- 9233975
TI  - Outcome of small-for-gestational age and appropriate-for-gestational age infants
      born before 27 weeks of gestation.
AB  - OBJECTIVE: To evaluate the consequences of being small-for-gestational age at
      extremely low gestational age. METHODOLOGY: Comparison of two historical cohorts
      of small-for-gestational age (SGA) and appropriate-for-gestational age (AGA)
      infants born between 24 and 26 6/7 weeks of gestation (gestational age estimated
      by early ultrasound at 16 to 18 weeks). Data were collected retrospectively on
      191 successive admissions to the neonatal intensive care unit between January 1,
      1983, and December 31, 1992. These included: demographic and maternal
      information, delivery mode and condition at birth, mortality, neonatal intensive
      care unit morbidities (respiratory distress syndrome, intraventricular
      hemorrhage, patent ductus arteriosis [PDA], chronic lung disease [CLD],
      retinopathy of prematurity [ROP], necrotizing enterocolitis, infection),
      nutrition, and length of hospitalization. RESULTS: Forty-one (21%) of the 191
      infants were classified as SGA. Those with congenital anomalies (10% in the SGA
      and 2% in the AGA group) were excluded from further analysis. Despite a similar
      rate of respiratory distress syndrome (50%), the SGA infants had a greater rate
      of failure of indomethacin treatment for PDA closure (54% vs 32% for AGA), a
      higher risk for CLD defined as a need for supplementary oxygen at 36 weeks (65%
      vs 32% for AGA), a more prolonged need for oxygen supplementation and ventilatory
      support (94 days vs 68 days for AGA and 58 days vs 40 days for AGA,
      respectively). SGA infants were also at greater risk for developing severe ROP
      (stage >/=III) (65% vs 12% for AGA). CONCLUSIONS: For infants born before 27
      weeks, being small-for-gestational age confers additional risks for severe
      morbidity, ie, PDA ligation, CLD, and ROP.

PMID- 9233976
TI  - Treatment of childhood syndrome X.
AB  - OBJECTIVE: Hyperinsulinemia, hyperlipidemia, hypertension, and coronary artery
      disease comprise a quartet known as Syndrome X. This syndrome was first described
      in adults, but has recently been described in children and adolescents. The
      purpose of our study was to determine if diet or exercise is able to change the
      clinical profile of Syndrome X in children. STUDY DESIGN: We recruited 36 obese
      (% ideal body weight = 170.3 +/- 31.1), children (9 to 12 yrs old) known to have
      high fasting cholesterol levels (177.5 +/- 33.5 mg/dL). Each participated in a 6
      week protocol in one of three groups: control (C), diet (D), or exercise (E).
      Twenty-five of the patients completed the study with full compliance. At the
      beginning and end of the study, we measured weight, height, blood pressure, serum
      insulin, and a lipid profile including: cholesterol, low density lipoprotein,
      high density lipoprotein (HDL), triglycerides, and apolipoprotein A (ApoA). All
      subject groups were similar before the study. The D group had the greatest
      attrition (40%) and all of the E group completed the study. RESULTS: After the 6
      week study period, there was no significant weight loss or change in body mass
      index for any group. There was no significant change in blood pressure and there
      was no significant decline of fasting cholesterol or low density lipoprotein
      levels in any of the groups. HDL levels were low in all groups and did not
      significantly change with treatment. There was a significant decline in the
      triglyceride levels in both the diet and exercise groups after the study (preD =
      150 +/- 60; postD = 122 +/- 50; preE = 165 +/- 50; postE = 116 +/- 39). Both the
      D and E groups also demonstrated a significant decrease in ApoA levels (preD =
      174 +/- 33; postD = 142 +/- 24; preE = 200 +/- 50; postE = 161 +/- 23). Most
      impressively, fasting insulin levels significantly decreased with both diet and
      exercise, but did not change in controls during the 6 weeks (preC = 52 +/- 19;
      postC = 53 +/- 21; preD = 54 +/- 23; postD = 15 +/- 8; preE = 48 +/- 21; postE =
      9). CONCLUSIONS: The findings of this study are consistent with previous studies
      describing the presence of Syndrome X in childhood. Both diet and exercise were
      effective in lowering triglyceride, ApoA levels, and insulin levels. However, due
      to the large rate of noncompliance in the diet group, exercise seems to be the
      best treatment for improvement in Syndrome X in children.

PMID- 9233977
TI  - Consequences of getting the head covered during sleep in infancy.
AB  - OBJECTIVE: To study the consequences of getting the head covered by bedding
      (fiber quilt) on carbon dioxide (CO2) accumulation around the face, behavior, and
      physiologic responses during prone and supine sleep in infants to add
      understanding to why victims of sudden infant death syndrome are often found
      under the bedding. METHPDOLOGY: Of 33 healthy term, usually nonprone sleeping
      infants, behavior and computerized polysomnography were successfully recorded for
      30 during prone and supine sleep at 21/2 months and for 23 prone and 25 supine at
      5 months. RESULTS: For both ages and body positions, covering the head resulted
      in significant CO2 accumulation around the face, fewer apneas (3 to 10 seconds),
      shorter duration of apneas after sighs, higher heart and respiratory rates, and
      peripheral skin temperature. Differences were generally greater at 21/2 than at 5
      months. While covered, the prone position was associated with higher CO2 levels
      close to the face, slightly higher transcutaneous PCO2, and higher heart rates
      and peripheral skin temperatures than the supine position. In the supine position
      23% were able to remove the cover from the head at 21/2 and 60% at 5 months,
      whereas only 1 infant of 5 months managed to remove the cover when prone.
      CONCLUSIONS: The observed responses are consistent with a potential for distress
      when the head is covered, particularly when placed prone. Probably most important
      with respect to sudden infant death syndrome is the infants' inability to remove
      the bedding from the head upon awakening from prone sleep.

PMID- 9233978
TI  - Maltreatment of children born to women who used cocaine during pregnancy: a
      population-based study.
AB  - BACKGROUND: Previous studies of maltreatment of children born to women who used
      cocaine during pregnancy have relied on either selected samples of infants
      identified at birth or biased, high-risk samples referred to protective services.
      OBJECTIVE: To determine the relative risk of either maltreatment or placement
      outside the home during the first 2 years of life in children born to women who
      used cocaine during pregnancy compared with a sociodemographically similar
      comparison group. PATIENTS: We reviewed the medical records of consecutive
      deliveries at Yale-New Haven Hospital from August 1, 1989 through September 30,
      1990. Of the 1140 women who were eligible for the study, 173 had a positive
      history and/or a positive urine test for cocaine; 139 of the infants were
      included in the study. A comparison group of infants was chosen from 526 women
      whose obstetric records indicated that they had not used cocaine during pregnancy
      based on at least two separate notations in the record. For each of the 139
      cocaine-exposed infants, an infant was chosen from the comparison group based on
      seven matching characteristics: date of birth, race, method of payment for the
      hospitalization, gestational age, mother's parity, mother's age at delivery, and
      timing of the first prenatal visit. MAIN OUTCOME MEASURES: Children's medical
      records at the only two hospitals in the region, the two neighborhood health
      centers, and the only health maintenance organization were reviewed from birth to
      2 years of age. Each injury was classified by two independent reviewers who used
      predefined criteria to distinguish maltreatment (physical abuse, neglect, or
      abandonment) from unintentional injuries. Placements outside the home were
      categorized according to whether the placement was in foster care or with a
      relative. MAIN RESULTS: The children were mainly African-Americans (80%), and
      most were enrolled in Medicaid (96.5%). By 2 years of age, 9.3% of the infants in
      the cocaine-exposed group versus 1.4% in the comparison group had been maltreated
      [matched relative risk = 6.5; 95% confidence interval (CI) = 1.47, 28.80], and
      25.9% vs 8.6% had spent some time in placement (matched relative risk = 5.0; 95%
      CI = 2.08, 12.01). After controlling for differences between the groups in
      baseline clinical and social variables, the adjusted odds ratios for both
      maltreatment (3.98; 95% CI = .81, 22.80) and placement (1.66; 95% CI = .74, 17.
      83) decreased and were no longer statistically significant. CONCLUSION: In this
      population-based study, children born to women who used cocaine during pregnancy
      were at a substantially increased risk of maltreatment or placement outside the
      home compared with a sociodemographically similar comparison group. Differences
      in baseline variables between the two groups, however, partially accounted for
      this increased risk. Therefore, a mother's use of cocaine is more likely a marker
      of increased risk rather than a single explanatory variable.

PMID- 9233979
TI  - Comparative analysis of pediatric mailing lists on the Internet.
AB  - OBJECTIVE: To analyze quantitative aspects and the relative quality of various
      pediatric discussion groups on the Internet and to contrast them with qualitative
      aspects of a selected number of pediatric journals. MATERIAL AND METHODS: An
      extensive number of mailing lists on the Internet of interest to pediatricians
      was compiled. Twelve of them concerned with pediatric specialties were selected.
      Six representative journals of pediatric specialties were also analyzed and
      compared with the corresponding mailing lists. From the list of subscribers we
      studied the potential quality of each mailing list. The postings sent by each
      member to the on-line discussions were also analyzed. As an estimate of the
      standing as author of each list member as well as of each first author of the
      selected journals, we calculated several indexes of quality using the 1995
      Medline database and the impact factors of the biomedical journals reported by
      the 1994 Science Citation Index. RESULTS: The most popular lists were NICU-NET
      and PICU, both having more than 1100 subscribers. PEDPATH and PEDIHEART had the
      highest percentage of subscribers who were published authors, and their papers
      also yielded the highest impact factors. The most active lists were NICU-NET and
      PICU. The most participative ones were CHILD-NEURO and PED-LUNG. CHILD-NEURO had
      the highest percentage of authors among the participants. PEDPATH and CHILD-NEURO
      had the authors with the highest impact factors among the people who participated
      in the discussions. These latter two lists also showed the highest impact factor
      per posting. Those which had the highest yield (highest activity with highest
      quality per posting) were CHILD-NEURO and PEDIHEART. The average impact factor
      per first author of the analyzed journals was always higher than the average
      impact factor per participant of the lists. CONCLUSIONS: The electronic-mail
      discussion groups on the Internet are new nonacademic forums in which knowledge
      and experience in pediatrics can be shared. They cannot replace but they
      complement other more academic sources such as medical journals.

PMID- 9233980
TI  - Evolution in the recognition of infantile hypertrophic pyloric stenosis.
AB  - PURPOSE: To analyze changes in the clinical condition at presentation and methods
      of establishing the diagnosis of infantile hypertrophic pyloric stenosis (IHPS).
      METHODS: Retrospective review of patients who underwent pyloromyotomy (PM) for
      suspected IHPS at two institutions from 1969 through 1994 was performed. For the
      purposes of comparison, the population was divided into five equal time periods.
      RESULTS: Over the 25-year period, 901 infants underwent PM. Patients presented at
      a younger age, weighed more, and had a shorter length of illness in the most
      recent time period. Hypochloremic alkalosis was found half as frequently in the
      most recent time period compared to the earliest group. A palpable pyloric tumor
      was present in 79% of patients in the earliest time period compared with 23% in
      the most recent time period. Sixty-one percent of patients in the earliest group
      and 96% in the latest group underwent an imaging study, reflecting the referring
      physician's evaluation before referral to the surgeon. CONCLUSIONS: Currently,
      patients with IHPS less frequently present with the clinical hallmarks of the
      disease. The use of imaging studies to establish the diagnosis has become common
      practice. The result has been the diagnosis of IHPS before alkalosis has
      developed, a shorter clinical course, less morbidity, and a shorter postoperative
      hospital stay.

PMID- 9233981
TI  - Auxiliary liver transplant in fulminant failure.
AB  - Fulminant hepatic failure (FHF) is defined as a syndrome of acute liver failure
      with the development of hepatic encephalopathy and severe hypoprothrombinemia
      occurring within 2 months of the onset of symptoms or jaundice in a person
      without preexisting liver disease. Total orthotopic liver transplantation (OLTX)
      is a lifesaving therapeutic option for patients with FHF, but currently requires
      lifelong immunosuppression to maintain the graft. Auxiliary partial orthotopic
      liver transplantation (A-OLTX) is a procedure whereby only a portion of the
      native liver is removed, and the remainder of the native liver is left in situ. A
      OLTX provides temporary support until the native liver recovers and
      immunosuppression can be withdrawn. We describe the successful application of
      emergency A-OLTX in a young girl who accidentally ingested Amanita phalloides
      mushrooms and developed FHF.

PMID- 9233982
TI  - Atrial flutter: an uncommon pediatric manifestation of hyperthyroidism.
AB  - OBJECTIVE: Atrial flutter is an uncommon arrhythmia in the pediatric population
      except for the immediate newborn period or following atrial repair of congenital
      heart disease. In children the diagnosis of atrial flutter may be difficult,
      attributable to rapid atrioventricular conduction and superimposition of flutter
      waves on QRS and T waves. Atrial flutter secondary to hyperthyroidism has been
      rarely reported in older adults, but there are no reports of children presenting
      with atrial flutter as the initial manifestation of hyperthyroidism. CASE REPORT:
      We report an interesting case of hyperthyroidism in a 3-year-old presenting with
      congestive heart failure and atrial flutter with 1:1 atrioventricular conduction.
      The responses to adenosine administration and to cardioversion were unusual and
      ultimately helpful in suggesting the diagnosis of hyperthyroidism. CONCLUSION:
      When atrial flutter is encountered in a pediatric patient in whom there is 1:1
      atrioventricular conduction, a lack of a response to adenosine, and persistent
      sinus tachycardia after cardioversion, the clinician should be alert to the
      possibility of thyrotoxicosis.

PMID- 9233983
TI  - Expression of glial markers in a retinal precursor cell line.
AB  - PURPOSE: To determine glial characteristics of the retinal precursor cell line
      R28, which has previously been shown to express proteins immunoreactive with
      photoreceptor markers IRBP, S-Ag, recoverin, the ganglion cell marker 2G12, as
      well as the Muller cell marker RetG1. METHODS: R28, an immortalized retinal
      precursor cell line derived from P6 rat retinal tissue, was analyzed to determine
      expression of glial cell markers. R28 cells were analyzed both
      immunocytochemically and by western immunoblot for GFAP, S-100, and vimentin.
      These results were compared with the primary postnatal day 6 retina. Double
      fluorescence immunolabelling was used to identify R28 cells which simultaneously
      expressed vimentin and the photoreceptor marker IRBP (interphotoreceptor retinoid
      binding protein). RESULTS: GFAP, S-100 and vimentin immunoreactive proteins were
      detected in R28 cells. Western blot analysis showed the GFAP immunoreactive band
      to migrate at a slightly higher apparent molecular weight for R28 than for P6
      retina, and demonstrated a less fibrillary staining pattern than P6 retina, but
      appeared to be present to some degree in all R28 cells. Variations in molecular
      weight were seen for S-100, although the nuclear staining pattern was the same
      for both the R28 cell line and P6 retina. S-100 immunoreactivity was seen in
      approximately 50% of the R28 cell population. Vimentin was expressed by virtually
      all R28 cells, and to a greater degree than that seen in P6 retina (both in cell
      number and intensity). Double labelling studies revealed R28 cells which
      expressed both vimentin and IRBP simultaneously. CONCLUSIONS: There is a very
      strong glial component to the R28 retinal precursor cell line, as evidenced by
      the expression of proteins immunoreactive to GFAP, S-100 and vimentin. However,
      even the most strongly immunoreactive marker vimentin was compatible with co
      expression of the photoreceptor marker IRBP as evidence of the "multi-phenotypic"
      nature of the precursor-like R28 cells. Ongoing studies will assess the
      differentiation potential of R28 cells and applicability in future studies of
      retinal cell differentiation and gene expression.

PMID- 9233984
TI  - Cloning and characterization of the cDNA encoding the alpha-subunit of cGMP
      phosphodiesterase in canine retinal rod photoreceptor cells.

PMID- 9233985
TI  - RPGR: part one of the X-linked retinitis pigmentosa story.

PMID- 9233986
TI  - The gene for PEDF, a retinal growth factor is a prime candidate for retinitis
      pigmentosa and is tightly linked to the RP13 locus on chromosome 17p13.3.

PMID- 9233987
TI  - Yeast silencers create domains of nuclease-resistant chromatin in an SIR4
      dependent manner.
AB  - Previous analysis of the repression of the silent mating type loci in
      Saccharomyces cerevisiae has linked the mechanism of silencing to the formation
      of a chromatin domain at the silenced loci. In this study, a TRP1 reporter gene
      was used to examine changes in chromatin structure in a neutral environment. This
      enabled the chromatin structure organized by yeast silencers to be compared
      directly with changes effected by the yeast alpha2 repressor. It was found that
      silencers mediate the formation of lengthy nuclease-resistant domains on the DNA,
      rather than specifically positioning nucleosomes over promoter regions as the
      alpha2 repressor does. Silencing at the TRP1 reporter gene closely resembled
      silencing at the HMR and HML loci. Repression of the test gene was optimal when
      two silencers flanking the reporter gene were used, mimicking the situation at
      the silent loci. In addition, both repression of the reporter gene and the
      formation of nuclease-resistant chromatin domains was SIR4 dependent.

PMID- 9233988
TI  - Hamster chromosomes containing amplified human alpha-satellite DNA show delayed
      sister chromatid separation in the absence of de novo kinetochore formation.
AB  - The centromeres of human chromosomes contain large amounts of the tandemly
      repeated alpha-satellite DNA family. Previous studies have shown that integration
      of alpha-satellite DNA into ectopic locations in mammalian chromosomes can result
      in the de novo formation of several features of centromeric function. Here we
      further examine the possible centromeric properties of alpha-satellite DNA by
      introducing it into hamster chromosomes. A large amplified region of ectopic
      alpha-satellite DNA was shown to direct binding of anticentromere antibodies
      (ACAs) and centromere protein B (CENP-B). The chromosome containing these ectopic
      arrays showed a high frequency of formation of anaphase bridges. Owing to the
      favourable morphology of these chromosomes, we were able to determine that this
      bridging was due to delayed sister chromatid disjunction at the location of the
      ectopic alpha-satellite, and not due to de novo formation of a fully functional
      kinetochore. A separate hamster cell line containing large tandemly repeated
      amplicons including the DHFR gene also displayed similar behaviour during
      anaphase. These results may support a role for alpha-satellite DNA in sister
      chromatid cohesion at centromeres. However, other repetitive DNA in favourable
      configurations appears to be capable of mimicking this behaviour during anaphase.

PMID- 9233989
TI  - A novel Mr 77,000 protein of the XY body of mammalian spermatocytes: its
      localization in normal animals and in Searle's translocation carriers.
AB  - We describe a novel XY body protein of rat and mice pachytene spermatocytes
      called XY77. Biochemical characterization showed that protein XY77 (Mr 77,000; pH
      value 8.3) is present in meiotic but absent in postmeiotic stages of
      spermatogenesis. With the aid of an antibody against protein XY77 together with
      another specific for XY body-associated protein XY40 we also investigated the
      localization of these proteins in mice carrying Searle's translocation, a
      reciprocal X-autosomal translocation. We show here that in these mice the
      distribution of both XY77 and XY40 is abnormal. Our results indicate that in
      Searle's translocation alterations are not restricted to the translocated
      autosome, but also involve chromatin segments corresponding originally to the sex
      chromosomes X and Y.

PMID- 9233990
TI  - Fluorescent in situ hybridization (FISH) analysis of the relationship between
      chromosome location and nuclear morphology in human neutrophils.
AB  - Human neutrophil nuclei typically consist of three of four large heterochromatic
      lobes joined by thin, DNA-containing filaments. In addition, some lobes exhibit
      appendages of various sizes and shapes. Classical genetic and cytological studies
      suggest that some appendages contain specific chromosomes. The studies reported
      here provide the first detailed analysis of the spatial relationship between
      individual chromosomes and recognizable structures in neutrophil nuclei using
      fluorescent in situ hybridization. Analysis of DNA sequences in chromosomes 2,
      18, X, and Y demonstrate that specific lobes in a population of neutrophil nuclei
      do not have a fixed chromosome content. This result implies that chromosomes
      partition randomly among lobes during neutrophil differentiation. However,
      neutrophil nuclear topography is not entirely fortuitous. For instance, none of
      the sequences probed in this study mapped to a filament and most centromeres lie
      in clusters near the nuclear periphery. In addition, one of the X chromosome
      centromeres in females and the Y chromosome centromere in males consistently
      associate with specific nuclear appendages found in a subset of neutrophil
      nuclei. Chromosomes 2 and 18 occupy discrete nd separate territories within
      individual lobes and neither territory ever extends into a filament.
      Surprisingly, the sizes of these territories are not proportional to chromosome
      length, suggesting that individual neutrophil chromosomes vary in their degree of
      compaction. These results are discussed in the light of models that attempt to
      explain nuclear morphology in terms of chromosome spatial organization.

PMID- 9233991
TI  - Evidence for two successive pericentric inversions in sex lampbrush chromosomes
      of Rana rugosa (Anura: Ranidae).
AB  - The objective of this study was to clarify the course of inversions by which a ZW
      sex chromosome dimorphism has become established in Rana rugosa. Fortunately, R.
      rugosa preserves three different forms of sex chromosomes in the several isolated
      populations. In both males and females, the homomorphic sex chromosomes from
      Hiroshima were closely similar to Z, while those from Isehara were slightly
      different from the Z. Females from Hirosaki demonstrated heteromorphic sex
      chromosomes. In this study, the configuration and pairing behavior of sex
      lampbrush chromosomes were examined in the female offspring produced from a cross
      between a female from Hiroshima and a male from Isehara, as well as the female
      offspring of a female from Hirosaki and the male from Isehara. For the sex
      lampbrush chromosomes from Hiroshima and Isehara, chiasmata were exclusively
      formed between the distal regions of the long arms of one sex chromosome and the
      terminal regions of the short arms of the other. As a result, landmarks arranged
      in reverse order were observed in the achiasmatic regions of these chromosomes.
      For the sex lampbrush chromosomes from Isehara and Hirosaki, on the other hand,
      chiasma formation was mainly confined to the lower half of the chromosomes
      corresponding to the long arms, and the landmarks in the achiasmatic regions of
      these chromosomes were disposed in the opposite direction to each other. These
      results seem to indicate that in the primitive sex chromosomes of the Hiroshima
      type two pericentric inversions occurred, leading to the differentiation of the W
      chromosomes. This is the first report to substantiate the process of sex
      chromosome differentiation experimentally.

PMID- 9233992
TI  - Colchicine effects on meiosis in the male mouse. I. Meiotic prophase: synaptic
      arrest, univalents, loss of damaged spermatocytes and a possible checkpoint at
      pachytene.
AB  - Antimitotic agents administered at the time of synapsis (leptotene/zygotene) have
      been shown to induce synaptic abnormalities visible during pachytene in the male
      mouse. The object of this study was to test the hypothesis that cells with
      relatively large amounts of colchicine-induced damage to the synaptonemal complex
      (SC) are eliminated from prophase whereas cells with relatively small amounts of
      SC damage proceed through to the end of prophase. Male mice were injected with
      tritiated thymidine to mark a cohort of spermatocytes at premeiotic S-phase for
      tracking through pachytene. Forty-eight hours later, when those cells were at
      leptotene/zygotene, colchicine was administered intratesticularly. Whole-mount SC
      spreads were made from animals sacrificed at various times following colchicine
      administration, and prepared for autoradiography. The marked cells were examined
      by light and electron microscopy and the kind and number of synaptic
      abnormalities were scored throughout pachytene. Colchicine-induced SC damage
      included single axial elements (univalents), together with partially synapsed and
      nonhomologously synapsed SCs. The amount of SC damage (amount and type per cell
      and frequency of cells with damage) scored at early pachytene exceeded by three-
      to fivefold the amount at late pachytene. This is consistent with spermatogenic
      cell loss from the seminiferous tubule via colchicine-induced destruction of
      Sertoli cell microtubules. The presence of spermatocytes with no more than four
      autosomal univalents at late pachytene indicates that some cells with low amounts
      of synaptic damage progress to the end of pachytene. The loss of the most
      severely damaged cells may represent a meiotic checkpoint at early pachytene in
      the male mouse.

PMID- 9233993
TI  - Histone H4 acetylation in plant heterochromatin is altered during the cell cycle.
AB  - Using polyclonal antibodies directed against acetylated isoforms of histone H4
      (H4 acetylated at lysine positions 5, 8, 12, 16 and H4 tetraacetylated), indirect
      immunofluorescence revealed hyperacetylation for all H4 variants at the nucleolus
      organizer region (NOR) of metaphase chromosomes of the field bean Vicia faba. The
      transcriptionally inactive and late-replicating heterochromatin regions proved to
      be hypoacetylated at lysine positions 5, 8 and 12. The remaining chromatin showed
      average fluorescence. These patterns were altered when deacetylase was blocked by
      exposure of root tip meristems to trichostatin A for more than 2 h prior to
      fixation. Under these conditions, all lysine positions, except lysine 8, appeared
      to be hyperacetylated at the NOR and in addition at the prominent heterochromatin
      domains. This observation represents a hitherto unique switch of histone
      acetylation pattern during the cell cycle. This is apparently caused by
      deposition of acetylated H4. Ac5, 12 and 16 or by acetylation directly after
      replication, which later on becomes reduced (H4.Ac16) or even reversed (H4.Ac5
      and 12) by deacetylase before cells enter mitosis.

PMID- 9233994
TI  - Beta-cell behavior during the prediabetic stage. Part I. Beta-cell
      pathophysiology.
AB  - beta-Cell function in non-insulin dependent diabetes mellitus (NIDDM) or type II
      diabetes, in particular during the prediabetic stage, has been more extensively
      investigated than in insulin-dependent diabetes mellitus (IDDM) or type I
      diabetes. Recently, however, the existence of a beta-cell dysfunction, early
      during the prediabetic stage of IDDM, and its possible contribution to the
      amplification of the autoimmune reaction have been underlined. Here, in a first
      of two parts, an attempt is made to review the various ways normal beta cells
      cope with increased demands on their resources in different models of
      hyperglycaemia in order to better delineate and compare the mechanisms
      implicating beta cells in the pathogenesis of both types of diabetes.

PMID- 9233995
TI  - Multicentre evaluation of the DCA 2000 system for measuring glycated haemoglobin.
      DCA 2000 Study Group.
AB  - The recommended method for assessing long-term blood glucose control in diabetic
      patients is the measurement of glycated haemoglobin (Hb). The Ames DCA 2000
      system for assaying glycated Hb uses an immunoassay with a monoclonal antibody
      specific for an aminoacid sequence within the HblAc molecule. This study compared
      the performance of the DCA 2000 system for HblAc measurement with that of high
      performance liquid chromatography (HPLC). A total of 1.016 insulin-dependent and
      non-insulin-dependent diabetic patients from 5 outpatient clinics took part. The
      correlation coefficients between DCA 2000 and HPLC data ranged between 0.94 and
      0.98, depending on site. The mean variations and 95% confidence intervals for the
      differences between the results for each sample were: site A 0.172 (-1.186 to
      1.53), site B -0.275 (-1.317 to 0.767), site C -0.146 (-0.868 to 0.576), site D 
      0.088 (-0.864 to 0.688), and site E -0.251 (-1.099 to 0.597). The sensitivity of
      the DCA 2000 assay ranged between 80 and 94%, and the specificity between 88 and
      100%, depending on site. For pooled results, the correlation coefficient assayed
      by the two methods was 0.95. The mean variation was -0.116 and the 95% confidence
      interval -1.23 to 0.998. The sensitivity of DCA 2000 was 91%, and the specificity
      94%. DCA tended to underestimate HbAlc slightly as compared to HPLC. This study
      confirms the reliability of DCA 2000 for measuring glycated Hb. The system is
      easy to use and provides valuable information for the care of the diabetic
      patients.

PMID- 9233996
TI  - Hypertriglyceridaemia and Lewis (A-B-) phenotype in non-insulin-dependent
      diabetic patients.
AB  - A relationship between Lewis (a-b-) phenotype and the metabolic syndrome X has
      been suggested. We studied the frequency of Lewis (a-b-) phenotype in subjects
      with non-insulin-dependent diabetes mellitus (NIDDM) as well as the relationship
      between Lewis phenotype and lipid concentration in NIDDM patients. Lewis red
      blood cell phenotyping was done in 207 NIDDM subjects and 345 non-diabetic
      control subjects by immuno-agglutination with anti-Lewis a and b monoclonal
      antibodies. Among NIDDM patients, the proportion with the Lewis (a-b-) phenotype
      was significantly increased (23.6% vs 14.3%, p = 0.01), and this phenotype was
      associated with higher levels of triglycerides (2.40 +/- 2.58 vs 1.97 +/- 1.25, p
      = 0.03). This study shows a relationship between NIDDM and Lewis (a-b-)
      phenotype. Hypertriglyceridaemia in Lewis-negative NIDDM could suggest an
      increased risk of ischaemic heart disease for these subjects.

PMID- 9233997
TI  - Reversal of diabetes in non-obese diabetic mice by xenografts of porcine islets
      entrapped in hollow fibres composed of polyacrylonitrile-sodium
      methallylsulphonate copolymer.
AB  - Intraperitoneal xenografting of islets immunoprotected by semipermeable membranes
      is a potential method of avoiding rejection by reversal of diabetes without
      immunosuppression. In this preliminary study, a xenograft of porcine islets,
      immunoprotected in semipermeable hollow fibres composed of a hydrogel of a
      polyacrylonitrile-sodium methallylsulphonate copolymer (AN 69), was used to
      reverse autoimmune insulin-dependent diabetes mellitus (IDDM) in the NOD mouse. A
      diabetic state was maintained in all 46 NOD mice which received transplants of
      empty fibres. Transplantation of encapsulated islets reversed the diabetic state
      in 37% (18/54) of the recipients. In these mice, nonfasting blood glucose
      concentration decreased within 24 h. Glycaemia was kept below the diabetic
      control range and the initial pretransplant value for 6 weeks. Recipient NOD mice
      suffered from the severe insulitis characteristic of clinical diabetes,
      confirming that reversal of the hyperglycaemic state was due solely to the
      xenografts. Pretransplant glycaemia was slightly (p < 0.05) higher in mice which
      remained diabetic after grafts of fibre-containing islets than in animals which
      experienced reversal of hyperglycaemia after transplantation) for the peritoneal
      cavity of recipients which had returned to normoglycaemia after grafting with
      islet-containing fibres. In all 4 cases, the islets responded to glucose during a
      perifusion assay. In 2 out of 4 grafts removed from mice which remained
      hyperglycaemic after grafting with islet-containing fibres (11, 13, 15 and 27
      days after transplantation), no basal or stimulated insulin secretion was
      detectable. Histological sections of a total of 75 fibres retrieved from the
      peritoneal cavities of recipient NOD mice showed surrounding inflammation, with
      adherent cells, neovascularisation and fibrotic reaction. These preliminary
      results are promising for the continued development of this bioartificial
      pancreas for xenogeneic islet transplantation since they demonstrate that
      xenogeneic islets can survive in the autoimmune environment of the NOD mouse with
      spontaneous diabetes mimicking human IDDM).

PMID- 9233998
TI  - Congestive heart failure predicts the development of non-insulin-dependent
      diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania
      Group.
AB  - Congestive heart failure (CHF) is an insulin-resistant state which constitutes
      the main risk factor for the development of non-insulin-dependent diabetes
      mellitus (NIDDM). Our study investigated the predictive role of CHF on the
      development of NIDDM in 1,339 elderly subjects with a mean ( +/- SD) age of 74.2
      +/- 6.4 years. CHF had a 9.5% prevalence, and 14.7% of the subjects had NIDDM.
      After stratification by age, subjects between 80 and 84 years had the highest
      prevalence of CHF and a total of 29.6% of CHF patients had NIDDM. In multiple
      logistic regression analysis, CHF was associated with NIDDM [odds ration (OR) =
      2.0, 95% confidence interval (CI) - 1.6-2.5] independent of age, sex, family
      history of diabetes, body mass index, (BMI), waist/hip ratio, and diastolic blood
      pressure. When only untreated CHF patients were taken into account, the
      association between CHF and NIDDM was even stronger (OR = 4.0, 95% CI = 3.4-5.8).
      When untreated CHF patients were grouped into those with low (I and II) and high
      (III and IV) New York Heart Association (NYHA) classes, the association of CHF
      and NIDDM was stronger with the worsening of CHF. In a longitudinal study, CHF
      predicted NIDDM independently of age, sex, family history of diabetes, BMI,
      waist/hip ratio, systolic and diastolic blood pressure, and therapy for CHF (OR =
      1.4, 95% CI = 1.1-1.8). CHF was associated with a higher prevalence of NIDDM and
      was a risk factor for its development. Elevated FFA concentrations may play a
      pivotal role.

PMID- 9233999
TI  - Bioartificial pancreas containing porcine islets of Langerhans implanted in low
      dose streptozotocin-induced diabetic mice: effect of encapsulation medium.
AB  - Two encapsulation culture media without animal serum were compared for
      development of a bioartificial pancreas. Porcine islets were suspended in Hams
      F10 medium supplemented with 2% Ultroser (US) or in Ultraculture medium (UC) and
      encapsulated in hollow fibres composed of AN69 copolymer. The function of
      encapsulated islets was assessed by intraperitoneal transplantation of two fibres
      in streptozotocin-induced diabetic mice. In both groups of transplanted mice (US,
      n = 26; UC, n = 18), a significant decrease in plasma glucose concentration was
      observed three days after fibre implantation (from 21.9 +/- to 14.4 +/- 0.8
      mmol/l for US fibres and from 22.7 +/- 0.8 to 13.3 +/- 1.3 mmol/l for US fibres
      and from 22.7 +/- 0.8 to 13.3 +/- 1.3 mmol/l for UC fibres). Graft survival 17
      days after implantation was 61% for mice with UC fibres and 35% for those with US
      fibres (P = 0.0001). Intramuscular glucose tolerance tests were performed in
      these animals (US, n = 5; UC, n = 10), and a normal glucose pattern was observed
      in both groups of transplanted mice. The results show that a complete
      normalisation of blood glucose and glucose tolerance can be achieved by
      implantation of a bioartificial pancreas. Moreover, UC appears to be a more
      suitable encapsulation culture medium for porcine islets in vivo.

PMID- 9234000
TI  - Evidence of non-inert material in needles and cartridges following a single
      insulin injection with a pen.
AB  - Preliminary results of an observational study are described in 50 unselected
      diabetic patients treated with insulin pens. The study was conducted to detect
      the presence of unexpected material in needles and cartridges after a single
      insulin injection. The injection was done by a trained nurse with the patient's
      usual pen and insulin cartridge. Cytopathological examination was performed on
      the material obtained from the needles and found in cartridges after
      centrifugation. Non-inert material was found in 28% of needles and 58% of
      cartridges, including squama (18 and 50% respectively) and epithelial cells (20
      and 42% respectively). These data, which suggest a non-passive capture of
      biological material into the delivery system after injection, emphasise the rule
      of strictly individual use of insulin delivery systems, including cartridges. The
      precise impact of self-injection of this non-inert material on individuals during
      repeated pen injections remains uncertain.

PMID- 9234001
TI  - Coronary heart disease in type 2 diabetic patients: common and different risk
      factors in men and women.

PMID- 9234002
TI  - Postprandial treatment with Lispro insulin.

PMID- 9234003
TI  - Use of implantable insulin pumps: the EVADIAC position. Recommendations of
      ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic
      Diseases). Evaluation dans le Diabete du Traitement par Implants Actifs.

PMID- 9234004
TI  - In vivo studies of intrahepatic metabolic pathways.
AB  - In vivo studies of liver metabolism have long been limited to measurement by the
      balance technique or isotope dilution method of the amounts of substrates taken
      up or produced by the liver. New methods, based mainly on the use of stable
      isotopes, now allow important data to be obtained on intrahepatic metabolic
      pathways. Nuclear magnetic resonance and chemical biopsy of glucuronic acid by
      acetaminophen facilitate the study of glycogen metabolism. Chemical biopsies of
      liver glutamine by phenylacetate and of cytosolic acetylCoA by sulfamethoxazole
      provide important data respectively on Krebs cycle activity and gluconeogenesis
      and on lipogenesis and cholesterol synthesis. Mass isotopomer distribution
      analysis of molecules synthesised during infusion of 13C-labelled precursors
      allows an estimation of in vivo gluconeogenesis as well as cholesterol synthesis
      and lipogenesis. Finally, these metabolic pathways can be studied through the
      incorporation of deuterium from deuterated water in glucose, fatty acids and
      cholesterol. All these non-invasive techniques allow investigations to be
      undertaken in human beings to study the nutritional and hormonal regulation of
      liver metabolism in normal subjects and in pathological situations.

PMID- 9234005
TI  - The Glucose Evaluation Trial for Remission (GETREM): A European effort to
      evaluate insulin-dependent diabetes mellitus in the first year after diagnosis.

PMID- 9234006
TI  - Equine dentistry: evolution and structure.

PMID- 9234007
TI  - Equine dental tissues: a trilogy of enamel, dentine and cementum.

PMID- 9234008
TI  - Parathyroid hormone-related protein: a polyhormonal enigma.

PMID- 9234009
TI  - Equine viral arteritis in newborn foals: clinical, pathological, serological,
      microbiological and immunohistochemical observations.
AB  - Clinical, pathological, immunohistochemical, serological and microbiological
      findings are described for 2 geographically and temporally distinct equine
      arteritis virus (EAV) epidemics in newborn foals. Outbreak A occurred at a
      commercial Standardbred breeding facility; Outbreak B began in a group of
      research animals. Clinical signs were severe and primarily referable to the
      respiratory tract. Fever and leucopenia and/or thrombocytopenia were observed in
      foals surviving for more than 24 h. The most common gross pathological findings
      were limited to the respiratory tract. Common histopathological findings included
      interstitial pneumonia, lymphocytic arteritis and periarteritis with fibrinoid
      necrosis of the tunica media. Renal tubular necrosis was noted in 2 foals.
      Immunoperoxidase histochemistry combined with virus isolation was diagnostic in
      all cases.

PMID- 9234010
TI  - The relationship between the concentration of ionised calcium and parathyroid
      hormone-related protein (PTHrP[1-34]) in the milk of mares.
AB  - Once lactation is established in mares, there is little change in the ionised
      calcium concentration in their milk. In contrast, the concentration of PTHrP(1
      34) in the milk increases to a maximum level by the end of the second week of
      lactation, near which it remains for the rest of the lactation. As found in other
      species, the concentration of PTHrP(1-34) in mare's milk is considerably higher
      than that in plasma, sampled at the same time. No significant correlation could
      be demonstrated between the concentrations of PTHrP(1-34) and ionised calcium in
      the milk except during the last 10 weeks of lactation.

PMID- 9234011
TI  - A light microscopic and ultrastructural examination of calcified dental tissues
      of horses: 1. The occlusal surface and enamel thickness.
AB  - Gross and microscopic examinations were undertaken on 46 cheek (molar and
      premolar) and 4 incisor equine teeth that were fractured, or sectioned either
      with a lathe or diamond saw. Specimens were examined without treatment, after
      decalcification or acid etching, utilising light, and scanning and transmission
      electron microscopy. In some horses, the occlusal surface of the teeth were
      covered with an organic pellicle. The occlusal surface of the underlying equine
      enamel contained different wear patterns, including polished areas, local
      fractures, wedge-shaped pits, striations and depressions. Occlusal dentine showed
      depressions whose depth was related to its occlusal surface area, with larger
      surface areas having deeper depressions. The thickness of equine enamel varied
      greatly throughout its folds in the transverse plane, and was thickest in areas
      where folds were parallel to the long axis of the maxilla and mandible. Enamel
      thickness remained constant in the longitudinal plane (throughout the length of
      the tooth). Peripheral enamel was more deeply infolded in lower than in upper
      cheek teeth and this appeared to compensate for the absence of infundibula (deep,
      cup-like enamel indentations that are partially filled with cement) in the lower
      cheek teeth.

PMID- 9234012
TI  - A light microscopic and ultrastructural examination of calcified dental tissues
      of horses: 2. Ultrastructural enamel findings.
AB  - Ultrastructural examinations of defined 3 equine enamel types termed equine (Eq.)
      Types 1, 2 and 3 enamel, according to the transverse appearance of their enamel
      prisms and the amount and appearance of their interprismatic enamel. Eq. Type 1
      enamel contained alternating rows of oval shaped prisms and thick interprismatic
      enamel plates, and was found adjacent to the amelodentinal junction. Eq. Type 2
      enamel consisted of circular, 'keyhole' to 'horseshoe' shaped prisms with little
      or no interprismatic enamel and was located adjacent to the amelocemental
      junction. Eq. Type 3 enamel was composed of rounded prisms surrounded by large
      amounts of interprismatic enamel and was inconsistently present in a thin layer
      at the amelodentinal and amelocemental junctions. Prism decussation was seen in
      the thickest peripheral enamel of the upper cheek teeth but was present
      throughout incisor enamel therefore making incisors highly resistant to cracking.
      Scanning electron microscopic examination showed enamel crystals to be
      cylindrical shaped on transverse section; however, on transmission electron
      microscopic examination these crystals had shapes, ranging from near oval to
      rectangular and formed small subunits, with crystals diverging from each other at
      various angles.

PMID- 9234013
TI  - A light microscopic and ultrastructural examination of calcified dental tissues
      of horses: 3. Dentine.
AB  - Ultrastructural examinations of equine dentine found that dentinal tubules
      extended from the amelodentinal junction towards the pulp forming primary
      curvatures. The number of dentinal tubules/unit area and their diameters
      increased significantly from the amelodentinal junction towards the pulp
      cavities, particularly in regular secondary dentine, but irregular secondary
      (tertiary) dentine contained no dentinal tubules. Dentinal tubules contained
      odontoblast processes that appeared to extend as far as the amelodentinal
      junction, but due to iatrogenic loss during specimen preparation, odontoblasts
      were seldom found in regular secondary dentine. In primary dentine, the dentinal
      tubules were surrounded by large amounts of peritubular dentine that increased in
      diameter from the amelodentinal junction towards the junction of primary and
      secondary dentine. The site of the dentinal tubule within the peritubular dentine
      varied at different dentinal sites. Peritubular dentine was present in primary
      dentine only and was surrounded by a thin layer of intertubular dentine. When
      acid etched, peritubular dentine gave dentine a honeycomb appearance adjacent to
      the junction of primary and secondary dentine.

PMID- 9234014
TI  - A light microscopic and ultrastructural examination of calcified dental tissues
      on horses: 4. Cement and the amelocemental junction.
AB  - Ultrastructural examinations showed the diameter of cement lacunae to be greater
      in infundibular cement than in peripheral cement of upper cheek teeth, which in
      turn was greater than in the peripheral cement of the lower cheek teeth. However,
      numbers of lacunae/unit area remained similar in these 3 dentinal region. Two
      types of cemental hypoplasia were found in equine cheek teeth. The first type was
      termed central infundibular cemental hypoplasia and was confined to the central
      region of infundibular cement. The cement adjacent to these frequently large
      defects was very porous and contained large vascular channels. In recently
      erupted cheek teeth, these central infundibular cemental defects were filled with
      connective tissue. The size of these cemental defects, the relationships of such
      defects with the occlusal surface and the degree of porosity of cement
      surrounding these defects may be important in the development of cemental caries.
      The second type of cemental defect was found at the amelodentinal junction of
      both peripheral and infundibular cement and was termed junctional cemental
      hypoplasia and appeared as spaces varying from focal, to long narrow defects
      along the amelocemental junction with the adjacent cement of normal appearance.
      Peripheral cement was deposited both directly, i.e. on unresorbed or resorbed
      enamel surfaces or indirectly, where the cement was separated from enamel by a
      thin calcified layer. The surface of unresorbed enamel had a pitted appearance,
      with the bases of the pits formed by enamel prisms and the pit walls by
      interprismatic enamel. The cemental surface of resorbed enamel contained
      depressions of variable shapes and sizes. These depressions which are believed to
      be caused by the resorption of enamel by odontoclasts were both focal and diffuse
      and were more marked on the cemental surface of infundibular as compared to
      peripheral enamel.

PMID- 9234015
TI  - Severe polysaccharide storage myopathy in Belgian and Percheron draught horses.
AB  - A severe myopathy leading to death or euthanasia was identified in 4 Belgian and
      4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt
      weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with
      inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to
      severe increases in muscle enzyme levels. Clinical diagnoses included equine
      motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional
      myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal
      myelitis (one horse). Characteristic histopathology of muscle from affected
      horses was the presence of excessive complex polysaccharide and/or glycogen,
      revealed by periodic acid-Schiff staining in all cases and by electron microscopy
      in one case. Evaluation of frozen section histochemistry performed on 2 cases
      indicated that affected fibres were Type 2 glycolytic fibres. Subsarcolemmal and
      intracytoplasmic vacuoles were most prominent in 3 horses age 2-4 years, and
      excessive glycogen, with little or no complex polysaccharide, was the primary
      compound stored in affected muscle in these young horses. Myopathic changes,
      including fibre size variation, fibre hypertrophy, internal nuclei, and
      interstitial fat infiltration, were most prominent in 5 horses age 6-21 years,
      and the accumulation of complex polysaccharide appeared to increase with age.
      Mild to moderate segmental myofibre necrosis was present in all cases.

PMID- 9234016
TI  - Cortisol concentrations in post competition horse urine: a French and British
      survey.
AB  - The purpose of the present report was to estimate the population parameters of
      cortisol concentrations in urine, an endogenous hormone used as a 'doping' agent
      and for which an international threshold (1.0 micrograms/ml) has been proposed.
      Two data bases (French and UK) corresponding to 112 and 142 samples, respectively
      were considered. Urine was collected under specific post competition conditions.
      Cortisol concentrations were obtained by validated methods (HPLC for the French
      samples, and GC-MS for UK samples). No difference was observed between the 2 data
      sets and statistical analyses were carried out on the two merged files. The
      overall geometric mean cortisol concentration was 48 ng/ml. Distribution was not
      Gaussian. A log-normal distribution was not rejected (for P > 0.05). Using the
      log-normal distribution, it was calculated that the probability of exceeding a
      cortisol concentration in urine of 1.0 micrograms/ml was 1.1 x 10(-4). It was
      concluded that the actual international threshold is specific i.e. robust with
      regard to the risk of erroneously declaring an unmedicated horse as positive.

PMID- 9234017
TI  - An outbreak of abortion in mares associated with Salmonella abortusequi
      infection.
AB  - An abortion outbreak occurred in a herd of 38 horses, 26 of which were pregnant
      mares. Twenty-one mares aborted between 5-10 months of gestation. In no case were
      there indications of impending abortion. Pathoanatomical, histopathological,
      virological and bacteriological examinations were carried out on 4 aborted
      fetuses. Histopathology identified Gram-negative bacteria compatible with
      salmonella in all 4 placentae. By subsequent bacteriological examination
      Salmonella abortusequi was isolated as the single causative agent in each case.
      Nonmotile Salmonella abortusequi with antigenic formula 4,12:-:- was isolated
      from one of the 4 fetuses. The described episode of equine abortion clearly
      indicates that Salmonella abortusequi has not been eradicated from Europe as
      previously thought.

PMID- 9234018
TI  - Haematology and serum biochemistry evaluation in normal postpartum mares.

PMID- 9234019
TI  - Intranasal phenylephrine reduces post anesthetic upper airway obstruction in
      horses.

PMID- 9234020
TI  - Neospora encephalomyelitis and polyradiculoneuritis in an aged mare with
      Cushing's disease.

PMID- 9234021
TI  - Treatment of bacterial tarsal tenosynovitis and osteitis of the sustentaculum
      tali of the calcaneus in five horses.

PMID- 9234022
TI  - A new look at dietary carbohydrate: chemistry, physiology and health. Paris
      Carbohydrate Group.
AB  - The current view of dietary carbohydrates as simply providing us with energy is
      outdated. Because of their varied chemistry and physical form the rate and extent
      to which the different types are digested in and absorbed from the small
      intestine varies. This in turn leads to affects on satiety, blood glucose and
      insulin, protein glycosylation, lipids and bile acids. Some carbohydrates reach
      the colon where they are fermented and affect many aspects of large bowel
      function, colonocyte and hepatic metabolism. A new framework for classifying and
      measuring food carbohydrates is needed to allow a greater understanding of the
      role of individual species in health and to inform the public of their
      importance. A classification based primarily on molecular size (degree of
      polymerisation) into sugars, oligosaccharides and polysaccharides, is suggested,
      with sub-groups identified by the nature of the monosaccharides. Greater
      knowledge of the chemical and physical properties of carbohydrates allow a more
      precise relation with physiology and health to be drawn. The Carbohydrate Group
      met in Paris in December 1995 at the invitation of Gerard Pascal, Director of
      CNERNA. Financial support for the meeting was provided by CNERNA.

PMID- 9234023
TI  - Iron, folate and vitamin B12 status of an elderly South African population.
AB  - OBJECTIVES: To determine the prevalence of anaemia and the haemopoietic nutrient
      status of older mixed ancestry (coloured) South Africans. DESIGN: A cross
      sectional analytic study. SUBJECTS: A random sample of 200 non-institutionalized
      subjects aged > or = 65 y of age, resident in urban Cape Town, was drawn using a
      two-stage cluster design. METHODS: Trained fieldworkers interviewed subjects to
      obtain demographic and lifestyle data. Dietary intake was assessed using a
      validated food frequency questionnaire. Fasting blood samples were drawn for the
      determination of haematological parameters, serum vitamin B12, serum folate, RBC
      folate and a full blood count. RESULTS: The prevalence of anaemia was 13.9. Eight
      of the 26 cases of anaemia (31) were associated with suboptimal haemopoietic
      nutrient status; 2(25) and 3(38) cases of these 8 anaemic subjects had suboptimal
      vitamin B12 and folate status, respectively. Iron deficiency anaemia accounted
      for 5(63) of the subjects with nutrition-related anaemia. Ten men and two women
      (6.5 of subjects) had raised serum ferritin concentrations, half of whom had
      abnormal biochemical parameters indicative of alcohol abuse. CONCLUSIONS: Older
      coloured South Africans, particularly women, should be encouraged to eat diets
      with a high nutrient density and to consume adequate amounts of foods high in
      iron, folate and vitamin B12. Further investigation regarding the high prevalence
      of hyperferritinaemia found in the men in this population is indicated.

PMID- 9234025
TI  - Reproducibility of a food frequency questionnaire used in the New York University
      Women's Health Study: effect of self-selection by study subjects.
AB  - OBJECTIVE: The aim of the study was to investigate the reproducibility of a food
      frequency questionnaire (FFQ) used in a cohort of 14,290 women enrolled in the
      NYU Women's Health Study. DESIGN: A subset of 474 cohort subjects who completed
      the dietary questionnaire at baseline (FFQ-1) were approached again on the
      occasion of a second visit to the mammography study centre and asked to complete
      the questionnaire a second time (FFQ-2) two to four years after FFQ-1. Two to
      three months later the questionnaire was mailed to the subjects, and they were
      asked to complete it a third time (FFQ-3). SETTING: A breast cancer screening
      clinic. SUBJECTS: Of the 474 subjects selected, 100% completed the second
      questionnaire while only 56% completed and mailed back FFQ-3. This made it
      possible to compare the long-term reproducibility of dietary intake measurements
      and baseline dietary habits between the two groups of subjects 'respondents', who
      agreed to complete the questionnaire a third time, and 'non-respondents', who did
      not. RESULTS: Among respondents (56% of study subjects), energy-adjusted
      correlation coefficients for short-term reproducibility between FFQ-2 and FFQ-3
      ranged from 0.50-0.64 for nutrients, and from 0.44-0.67 for foods. The long-term
      reproducibility was lower, ranging from 0.36-0.53 for nutrients, and from 0.31
      0.48 for specific food groups. Among those who did not respond to FFQ-3, crude
      correlations for long-term reproducibility, unadjusted for energy intake, were
      generally lower than among respondents. Nevertheless, after adjustment for energy
      intake, correlations for long-term reproducibility (FFQ-2 to FFQ-1) were of
      similar magnitude in both groups. In addition, 'non-respondents' reported lower
      intake of fruit and vegetables and higher intake of meat. CONCLUSIONS: The
      results of this study suggest that subjects who volunteer to participate in
      substudies on the validity or reproducibility of dietary questionnaire
      measurements may tend to provide more accurate responses to the questionnaire.
      The phenomenon seems related more to accuracy of reporting of absolute intake
      levels than of the relative composition of diet, self-selection may be associated
      with differences in dietary habits.

PMID- 9234024
TI  - Diterpenes from coffee beans decrease serum levels of lipoprotein(a) in humans:
      results from four randomised controlled trials.
AB  - OBJECTIVE: Unfiltered coffee raises serum LDL cholesterol in humans, owing to the
      presence of the diterpenes cafestol and kahweol. Norwegians with a chronic high
      intake of unfiltered coffee also has elevated serum levels of lipoprotein(a), an
      LDL-like particle which is insensitive toward dietary interventions. We now
      experimentally studied the influence of coffee diterpenes on lipoprotein(a)
      levels. DESIGN: Four randomised controlled trials. SUBJECTS: Healthy,
      normolipidemic volunteers. INTERVENTIONS: Coffee, coffee oil, and pure diterpenes
      for 4-24 weeks. MAIN OUTCOME MEASURES: The circulating level of lipoprotein(a).
      RESULTS: In 22 subjects drinking five to six strong cups of cafetiere coffee per
      day, the median fall in lipoprotein(a) was 1.5 mg/dL after two months (P = 0.03),
      and 0.5 mg/dL after half a year (P > 0.05), relative to 24 filter coffee
      drinkers. Coffee oil doses equivalent to 10-20 cups of unfiltered coffee reduced
      lipoprotein(a) levels by up to 5.5 mg/dL (P < 0.05) in two separate trials (n =
      12-16 per group). A purified mixture of cafestol and kahweol, as well as cafestol
      alone, were also effective in reducing Lp(a) levels (n = 10). Averaged over the
      four trials, each 10 mg/d of cafestol (plus kahweol)--the amount present in two
      to three cups of cafetiere coffee--decreased Lp(a) levels by 0.5 mg/dL or 4% from
      baseline values after four weeks (n = 63). CONCLUSIONS: Coffee diterpenes are
      among the few dietary exceptions shown to influence serum lipoprotein(a) levels.
      However, the Lp(a)-reducing potency of coffee diterpenes may subside in the long
      run, and their adverse side effects preclude their use as lipoprotein(a)-reducing
      agents.

PMID- 9234026
TI  - Diet composition and body mass index in pre-school children.
AB  - OBJECTIVE: To investigate the relationship between diet composition and body mass
      index (BMI) in pre-school children. DESIGN: Reanalysis of data from the National
      Diet and Nutrition Survey of children aged 1.5-4.5 y. Height and weight of
      children were used to calculate Body Mass Index (BMI) and BMI standard deviation
      scores. Dietary intake data were used to calculate percentage of total energy
      intake derived from fat, carbohydrate and protein. These data were then divided
      into quintiles. The data were then analysed in order to assess if there was any
      relationship between the diet composition and BMI. SETTING: Community based
      project throughout Great Britain. SUBJECTS: 1444 children aged 1.5-4.5 y.
      MEASUREMENTS: Diet composition was assessed in terms of percentage energy derived
      from fat, protein and carbohydrate following a four day weighed intake carried
      out by the parents or carers of the child. Body size was assessed by measuring
      BMI and calculating the standard deviation score relative to UK reference data.
      RESULTS: There were no trends apparent using ANOVA and multiple regression that
      indicated that diet composition was related to body size. CONCLUSIONS: In a large
      cohort of pre-school children we are unable to confirm the recent findings in
      much smaller samples that diet composition affects body size. Other factors such
      as energy intake per se and levels of habitual physical activity might have a
      more important bearing on BMI in pre-school children.

PMID- 9234027
TI  - Body composition analysis by dual energy X-ray absorptiometry in female diabetics
      differ between manufacturers.
AB  - OBJECTIVE: Comparison of body composition results by two dual energy X-ray
      absorptiometry (DXA) instruments, namely QDR-2000 from Hologic Inc and from Lunar
      in subpopulations of lean and obese subjects. DESIGN: Cross-sectional study with
      85 female diabetics (BMI 18-43 kg/m2) measured with both DXA instruments.
      RESULTS: The regression lines for fat tissue mass (FTM), FAT% and total body bone
      mineral content (TBMC), but not lean tissue mass (LTM), were different from the
      line of identity (P < 0.01). However, the relationships were high (r2 > 0.95),
      and the corresponding SEE%'s were low (0.8-4.8%), and were independent of BMI.
      FTM and FAT% measured by the QDR-2000 were 10% higher, and LTM and TBMC 6% lower,
      than by DPX (P < 0.001). CONCLUSIONS: There were lack of agreements between total
      body composition results by DPX Lunar, and QDR-2000 Hologic Inc. Individual
      results on the two systems cannot be directly compared. Standardization of body
      composition measurements by DXA is strongly needed.

PMID- 9234028
TI  - Dietary fat reduction achieved by increasing consumption of a starchy food--an
      intervention study.
AB  - OBJECTIVE: To test t he hypothesis that increased consumption of foods in rich in
      starch, such as breakfast cereals, will enable a substantial reduction in the
      percentage dietary energy derived from fat. DESIGN: Parallel experimental design,
      with matched subjects allocated randomly to an intervention or a control group.
      SETTING: Free-living subjects (mean age 20 y), undergraduate students at a
      college for higher education. SUBJECTS: Sixty-two enrolled, 59 completed the
      study; 7 d weighed intakes at baseline, 4 weeks and 12 weeks. INTERVENTION: The
      intervention group were required to eat 60 g breakfast cereal daily with semi
      skimmed milk. Pre-weighed portions of three types of cereal were distributed
      without charge at the beginning of each week of the study; subjects were
      reimbursed for the cost of milk used. No other dietary advice was given. RESULTS:
      At baseline, total energy intake and percentage energy from macronutrients was
      very similar in both the intervention and control group. After four weeks of
      intervention there was a significant reduction in % energy from fat (-5.4%) in
      the experimental group, maintained at the 12 weeks follow-up. There was a
      corresponding rise in energy from CHO: a significant increase of 5.5% after four
      weeks had reached 6.5% by 12 weeks. Total energy remained virtually unchanged,
      indicating a replacement of fat energy by carbohydrate energy. These changes were
      not found in the control group. CONCLUSIONS: A simple dietary intervention to
      increase consumption of breakfast cereal led to a 5% reduction in % dietary fat
      energy, with a beneficial effect on micronutrient intakes. The results support
      the case for positive advice to increase consumption of complex carbohydrate, as
      a strategy for dietary fat reduction in the wider population.

PMID- 9234030
TI  - Dietary practices and lipid intake in relation to plasma lipid profile in Hong
      Kong Chinese.
AB  - OBJECTIVE: To study dietary lipid intake and plasma lipid profile of the Hong
      Kong Chinese population as part of a territory wide survey on cardiovascular risk
      factors. DESIGN: Randomised age and sex stratified survey. SUBJECTS: 1010
      subjects aged 25-74 y (500 men, 510 women). MEASUREMENTS: A food frequency method
      with food tables compiled for Hong Kong was used for nutrient quantitation, while
      a separate questionnaire was used to examine dietary practices. Plasma lipid
      profile was estimated using standard laboratory methods. RESULTS: Total calorie,
      fat, saturated fatty acid (SFA), poly- and mono-unsaturated fatty acid (PUFA and
      MUFA), and cholesterol intake were higher in men; however when adjusted for
      caloric intake no difference was observed. Men had lower intake of PUFA as
      percentage of total energy had a higher Hegsted Score compared with women.
      Subjects consuming beans twice or more per week had lower total cholesterol and
      LDL-cholesterol concentrations. Overall, the population dietary intake was close
      to the ideal for cardiovascular health: percentage fat not greater than 30% of
      the total calorie intake, saturated fat intake not greater than 10% of calories,
      and cholesterol less than 180 mg/1000 Kcal. CONCLUSION: The dietary pattern for
      Hong Kong Chinese appear to be satisfactory with respect to cardiovascular
      health.

PMID- 9234029
TI  - Women with insulin-dependent diabetes mellitus (IDDM) complicated by eating
      disorders are at risk for exacerbated alterations in lipid metabolism.
AB  - OBJECTIVE: To examine lipid parameters that are affected in women with insulin
      dependent diabetes mellitus (IDDM) who engaged in disordered eating behaviours.
      DESIGN: Randomized, unmatched. SETTING: Tertiary care. SUBJECTS: Ninety women (18
      46 y) with IDDM. INTERVENTIONS: Classification of subjects based on severity of
      eating disorder: clinical (n = 14), subclinical (n = 13) and control (n = 63).
      Blood was analysed for glycosylated haemoglobin (HbA1c) and serum for
      triglycerides and cholesterol. Carotenoid and tocopherol concentrations were
      analysed by high performance liquid chromatography (HPLC). Dietary intake was
      assessed by the National Cancer Institute food frequency questionnaire. RESULTS:
      HbA1c was significantly increased im women demonstrating clinical and subclinical
      symptoms compared to control (10.4 +/- 2.6, 10.0 +/- 1.5 and 8.3 +/- 1.6%,
      respectively, P < 0.05). Triglycerides concentrations were significantly
      increased in women with subclinical eating disorders compared to controls. In
      women who intentionally omitted or reduced insulin, triglyceride cholesterol and
      HbA1c were significantly increased compared to controls. Women with IDDM and
      eating disorders who exhibited bulimic behaviours consumed significantly more
      energy, total fat and cholesterol compared to controls and women with eating
      disorders who were restrained eaters. CONCLUSION: While IDDM is known to perturb
      lipid metabolism, these data demonstrate that eating disorders, in combination
      with IDDM, results in additional alterations in lipid metabolism.

PMID- 9234031
TI  - The effect of ascorbic acid on plasma lipids and oxidisability of LDL in male
      smokers.
AB  - OBJECTIVE: The aims of this study were to investigate the effect of ascorbic acid
      (AA) supplementation on the oxidisability of low density lipoprotein (LDL) in
      vitro and on plasma lipoproteins under controlled dietary conditions. DESIGN:
      Randomised single-blind cross-over trial. SETTING: Free living subjects.
      SUBJECTS: Eight male smokers (age: 25 +/- 2.4 y, BMI: 20.7 +/- 0.5, cigarettes
      per day: 19.1 +/- 2.4; means +/- s.e.). INTERVENTIONS: Dietary intake was
      determined in all subjects were advised to achieve an intake as close as possible
      to the recommended dietary intake of AA (40 mg). After two weeks on the baseline
      diet, subjects were asked to consume 1 g AA per day for two weeks followed by two
      weeks of placebo supplementation, or vice versa. In view of the carry-over
      effects of plasma AA, a wash-out period was incorporated between treatments.
      Duplicate venous blood samples were collected before and after supplementation
      and the plasma concentrations of AA, lipids and lipoproteins were determined. The
      in vitro copper-induced oxidisability of LDL was assessed by monitoring of the
      absorbance of 234 nm. RESULTS: No changes in the plasma lipids or the
      oxidisability of LDL were found after AA supplementation compared to placebo.
      Plasma AA concentrations doubled on average after supplementation indicating that
      the lack of effect was not a result of poor compliance. CONCLUSIONS: AA
      supplementation at this dose did not alter plasma lipids of LDL oxidisability in
      male smokers.

PMID- 9234032
TI  - High dose exercise does not increase hunger or energy intake in free living
      males.
AB  - OBJECTIVE: To examine the effects of a high dose (two high-intensity exercise
      sessions) of exercise on energy intake (EI) and subjective states (hunger and
      mood). DESIGN: Using a within subjects design, there were two treatment
      conditions, each of two consecutive days. SETTING: The Human Appetite Research
      Unit at Leeds University Psychology Department. SUBJECTS: Eight lean males who
      were regular exercisers were recruited from the student/staff population of Leeds
      University. INTERVENTIONS: The effects of the high dose of exercise Ex1 were
      compared with the effects on the day immediately after exercise (Ex2) and two
      consecutive days of no exercise (R1 and R2). EI was monitored using self-record
      food diaries and subjective states were tracked using a new Electronic Appetite
      Rating System (EARS). Heart rate and physical activity were also measured.
      RESULTS: Feelings of hunger were not elevated by the high dose of exercise on Ex1
      or on the day after exercise (Ex2). In fact, average daily feeling of hunger on
      Ex1 was significantly lower compared with the average daily feeling of hunger on
      Ex2 (t = 3.15, d.f. = 7, P < 0.05), but not when compared with R1 or R2. EI and
      macronutrient intakes were not different on Ex1, Ex2, R1 or R2. Therefore, there
      were no increase in EI on Ex1 or Ex2 to account for the measured increase in
      exercise-induced energy expenditure (1200 kcal). Continuously monitored heart
      rate and activity profiles indicated that there was no difference in activity
      during the non-exercise periods between the four days. CONCLUSIONS: This study
      indicates that a high dose of exercise in one day failed to have any effect on EI
      within the same day or on the day immediately after exercise, compared with days
      of no exercise. These results demonstrate that an acute but substantial increase
      in energy expenditure (EE) due to intense exercise does not automatically
      increase hunger or EI within 48 h. This indicates the absence of any strong
      coupling between EE and EI in the short-term, probably as a result of food intake
      being held in place by environmental contingencies and short-term pre-absorptive
      physiological responses arising from eating itself.

PMID- 9234033
TI  - Infant feeding practices reflect antecedent risk of xerophthalmia in Nepali
      children.
AB  - OBJECTIVE: To determine the relationship between infant feeding history and risk
      of xerophthalmia due to vitamin A deficiency (VAD) in early childhood. DESIGN: A
      case-control study of previously xerophthalmic and non-xerophthalmic children.
      SETTING: Rural lowland region of Nepal. SUBJECTS: One hundred and fifty-six
      children (aged 1-6 y old), half of whom previously had xerophthalmia due to
      vitamin A-deficiency, the other half matched by locale, age and the presence and
      age of a younger sibling (n = 102). METHODS: Xerophthalmia was determined by
      trained ophthalmic assistants on the basic of current Bitot's spots, corneal
      xerosis or report of night blindness. Infant feeding history was collected
      through a diet history method obtained from the mother of the focus child.
      Exploratory factor analysis was conducted to determine the presence of underlying
      patterns in infant feeding practices. Conditional logistic regression was used to
      estimate odds ratios. RESULTS: Mothers of control children tended to have a
      higher level of education (P < 0.10) and to have fewer children who had died (P <
      0.10) than mothers of case children. Feeding of meat (OR = 0.09, CI = 0.01-0.70)
      or fish (OR = 0.41, CI = 0.17-0.99) with liver, eggs (OR = 0.11, CI = 0.01-0.88)
      and mango (OR = 0.28, CI = 0.13-0.60) were protective in association with
      xerophthalmia in early childhood. Factor analysis uncovered several distinct
      patterns in infant feeding, which varied by age of the infant. Only the 'animal
      flesh' feeding pattern (factor), practiced in the second year of life, proved
      significantly protective from xerophthalmia (OR = 0.43, CI = 0.20-0.94). Feeding
      patterns of younger children closely paralleled those of their older siblings
      with and without VAD. CONCLUSIONS: The study supports the hypothesis that infant
      dietary practices can influence subsequent risk for VAD. Our findings emphasize
      the importance of introducing vitamin A-rich foods during weaning to reduce the
      risk of VAD-associated xerophthalmia in the later preschool years.

PMID- 9234035
TI  - Effects of alcohol intoxication on the perceived consequences of risk taking.
AB  - In 2 laboratory studies, the authors tested the hypothesis that intoxicated risk
      taking results from alcohol's effects on negative outcome expectancies. Young
      adults (N = 107) consumed alcohol or no alcohol and made ratings of the
      likelihood that negative and positive consequences would result from a variety of
      risky activities. Consistent with study hypotheses, participants rated negative
      consequences as less likely when they were intoxicated than when sober. Results
      were replicated in a second study (N = 88), which further showed that alcohol,
      rather than expectancy set, contributed to these reduced perceptions of risk.
      Findings provide the first experimental evidence that alcohol intoxication may
      contribute to risk-taking behavior be altering expectations about negative
      consequences.

PMID- 9234034
TI  - Effects of methylphenidate and expectancy of ADHD children's performance, self
      evaluations, persistence, and attributions on a cognitive task.
AB  - The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding
      medication on the performance and task persistence of 60 boys with attention
      deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo
      design, boys in 4 groups (received placebo/drug crossed with told placebo/drug)
      completed the task in success and failure conditions. Medication improved
      participants' task persistence following failure. Participants' task performance
      was not affected by whether they thought they had received medication or placebo.
      Children made internal attributions for success and made external attributions
      for failure, regardless of medication or expectancy. These findings confirm
      previous reports that it is the pharmacological activity of MPH that affects ADHD
      children's self-evaluations and persistence. The results contradict anecdotal
      reports that MPH causes dysfunctional attributions and confirm previous studies
      showing that medication does not produce adverse effects on the causal
      attributions of children with ADHD.

PMID- 9234036
TI  - Chlordiazepoxide counteracts activity-induced suppression of eating in rats.
AB  - Because benzodiazepines such as chlordiazepoxide increase food intake, the
      present experiments tested the effect of chlordiazepoxide on food intake in an
      animal model of anorexia nervosa, called activity anorexia (AA). To induce AA,
      rats (Rattus norvegicus) were maintained in activity wheels and restricted to a
      single 60-min feeding period each day. As previously found, this procedure
      suppressed food intake. After several days of this training, food intake was
      measured 30 min after the rats were injected with chlordiazepoxide (5 mg/kg) or
      saline. In 2 experiments, chlordiazepoxide counteracted the suppression of food
      intake produced by AA. Because benzodiazepines have been found to increase food
      intake in many mammalian species including primates, the present results suggest
      that benzodiazepines could be useful in the treatment of anorexia nervosa.

PMID- 9234037
TI  - Acute participant-rated and behavioral effects of alprazolam and buspirone, alone
      and in combination with ethanol, in normal volunteers.
AB  - The acute behavioral effects of buspirone (15 and 30 mg/70 kg), alprazolam (0.75
      and 1.5 mg/70 kg), and placebo, alone and in combination with ethanol (0-0.6
      g/kg), were tested in 13 volunteers. Ethanol alone produced only a few
      significant behavioral effects. Alprazolam and buspirone produced comparable dose
      related increases in participant ratings of sedation, but only alprazolam
      impaired performance. The buspirone-ethanol and alprazolam-ethanol combinations
      produced robust sedative-like participant-related drug effects that were similar
      in magnitude, but, in general, only the alprazolam-ethanol combinations impaired
      performance. These findings suggest that the participant-rated effects of
      therapeutic doses of buspirone in combination with moderate doses of ethanol are
      similar to those of therapeutic doses of alprazolam in combination with ethanol,
      but the performance-impairing effects of buspirone are distinguishable from those
      of alprazolam, alone and in combination with ethanol.

PMID- 9234038
TI  - Ability to counselors to detect cognitive impairment among substance-abusing
      patients: an examination of diagnostic efficiency.
AB  - Counselors (N = 12) in 1 of 2 substance abuse treatment facilities were asked to
      identify which of their patients (N = 97) had general neurocognitive impairment.
      Counselors were required to base their judgements on information collected from
      patients during psychosocial history gathering, clinical interviews, physical
      examinations, brief cognitive screening tests, and substance abuse severity
      evaluations, but not on neuropsychological test results. All patients were
      subsequently administered a neuropsychological test battery. Diagnostic agreement
      between counselors' impressions of patients' cognitive status and patients'
      actual neuropsychological test performance was poor. Subsequent analyses revealed
      counselors' impressions about patients' neuropsychological functioning were based
      on information that did not reliably discriminate between cognitively impaired
      and intact patients (e.g., years of education and self-reported symptoms of
      cognitive dysfunction).

PMID- 9234039
TI  - Changes in cigarette smoking not observed following repeated cocaine self
      administration.
AB  - Acute administration of some psychoactive drugs (e.g., cocaine, heroin, methadone
      d-amphetamine) has been found to increase spontaneous cigarette smoking for 1-3
      hr, but the effects of chronic drug administration have not been systematically
      studied. Computerized cigarette dispensers were used to study the effects of
      multiple daily cocaine administrations on cigarette smoking. Participants were 8
      (5 male) cocaine-dependent cigarette smokers who resided on a closed clinical
      research ward and smoked an average of 16.7 cigarettes per day during the week
      prior to starting the study. During test sessions on Monday, Wednesday, and
      Friday of each week, participants could obtain either cocaine (25 mg i.v.) on 2
      days or saline (1 ml i.v.) on the other day, 3 times per day at 2-hr intervals
      under double-blind conditions. The number of cigarettes dispensed during study
      days was analyzed in 2-hr increments. No significant cocaine effect was found.
      These findings fail to show a change in the number of cigarettes smoked after
      chronic cocaine self-administration over time intervals longer than 1-3 hr.

PMID- 9234040
TI  - Effects of nicotine dose and administration method on withdrawal symptoms and
      side effects during short-term smoking abstinence.
AB  - The effects of using several nicotine replacement treatments on self-reported
      withdrawal symptoms and side effects during 2-day periods of smoking cessation,
      with 5 days of ad lib smoking between cessation days, were evaluated.
      Participants (N = 18) experienced the following conditions: nicotine gum, 24-hr
      patch, 16-hr patch, 24-hr patch plus gum, double 24-hr patch, and no nicotine
      replacement. The present study found morning urge to smoke was greater during the
      16-hr than during the 24-hr patch condition. Double-patch use resulted in
      significantly greater insomnia than the smoking baseline and 16-hr patch
      conditions. The no medication and gum alone conditions resulted in similar
      withdrawal symptoms, and both tended to result in greater reported withdrawal
      symptoms than the smoking baseline condition. There were no significant
      withdrawal symptom differences between the 24-hr, patch-gum, and double-patch
      conditions. The 24-hr and double-patch conditions were preferred by two thirds of
      the participants (6 each).

PMID- 9234041
TI  - Stages and processes of change as predictors of drug use among methadone
      maintenance patients.
AB  - In this study the authors evaluated the predictive validity of stages-of-change
      and processes-of- change measures among methadone maintenance patients. One month
      after treatment entry, participants completed questionnaires providing stage and
      process scale scores regarding readiness to discontinue polydrug use.
      Participants also completed an algorithm assigning them to a stage category on
      the basis of their stated intentions regarding quitting. The algorithm predicted
      urinalysis results during a 12-week posttest period; however, only 1 stage scale
      (contemplation) and no process scales correlated significantly with outcome. In a
      hierarchical regression, stage and process scale scores significantly improved
      prediction of posttest abstinence beyond that afforded by baseline drug-free
      urine rates, but this effect was attributable to the contemplation scale alone.
      Despite their widespread use, stage and process scales have yet to demonstrate
      clearly predictive validity.

PMID- 9234042
TI  - Are choice and self-administration of marijuana related to delta 9-THC content?
AB  - The effects of delta 9-tetrahydrocannabinol (THC) content on choice marijuana,
      number of marijuana cigarettes smoked, and ratings of marijuana's effects were
      examined in 6 adult male marijuana smokers during a residential study consisting
      of four 3-day blocks of 2 sample days and 1 choice day. Days were divided into
      6.5-hr work and social-access periods, beginning at 1000 and 1700. On sample
      days, marijuana cigarettes containing different THC concentrations (0.0% vs. 3.5%
      and 2.0% vs. 3.5% THC) were smoked at least once during each period. On choice
      days, independent choices between previously sampled marijuana cigarettes were
      made during each period. A maximum of 8 cigarettes could be smoked per day, and
      drug ratings were obtained after each period. Only choice behavior was sensitive
      to changes in THC content, whereas only the number of smoked marijuana cigarettes
      was related to context (i.e., work and social-access period).

PMID- 9234043
TI  - Individual differences in the subjective effects of the first cigarette of the
      day: a self-report method for studying tolerance.
AB  - Some smokers are more sensitive than others to the subjective effects of
      cigarettes, especially the first cigarette of the day. This report explored self
      reported subjective effects to the first cigarette of the day and examined the
      extent to which heaviness of smoking and years smoking are associated with
      subjective effects. In 3 independent samples (ns = 254, 116, 86). self-reports of
      light-headedness from the first cigarette of the day decreased with increasing
      heaviness of smoking and increasing the number of years smoking, suggesting that
      differences in responses were due to differences in chronic tolerance. Because
      measures of the subjective effects of drugs are useful in the study of drug
      response variability, this self-report item on light-headedness should be
      included in further research on individual differences in the subjective effects
      of cigarette smoking.

PMID- 9234044
TI  - Sex differences in effects of predictable and unpredictable footshock on fentanyl
      self-administration in rats.
AB  - An operant conditioning paradigm was used to examine effects of predictable and
      unpredictable footshock on oral fentanyl (50 micrograms/ml self-administration
      (SA) in 12 female and 12 male Wistar rats (Rattus norvegicus). Rats were tested
      for drug SA under a progressive ratio schedule with and without repeated
      predictable or unpredictable footshock over 8 weeks. Female rats consumed greater
      amounts of fentanyl than did male rats. Male rats exhibited greater withdrawal
      behaviors following naloxone challenge. Predictable footshock with repeated
      exposure (i.e., chronic stress) was accompanied by greater fentanyl SA than was
      unpredictable footshock, particularly for female rats. Corticosterone levels were
      positively correlated with fentanyl SA. Predictability of the stressor also had a
      greater effect on maintenance of fentanyl SA than it did on relapse to fentanyl
      SA. Results suggest that sex plays an important role in drug-taking behavior by
      rats.

PMID- 9234045
TI  - Acute and chronic antidepressant drug treatment in the rat forced swimming test
      model of depression.
AB  - The forced swimming test (FST) is a widely used behavioral screen in rodents that
      is both sensitive and selective for clinically effective antidepressant drugs.
      However, antidepressant drugs produce changes in the FST within 24 hr of
      treatment, in contrast to weeks required for the recovery from clinical
      depression, and high doses seem to be required to produce effects in most animal
      tests. This study examined behavioral effects in the FST after subacute and
      chronic treatment with low doses (1-5 mg/kg) of antidepressant drugs to determine
      whether chronic treatment produced behavioral effects at doses that were
      ineffective after subacute treatment. The antidepressants studied were
      desipramine, a selective norepinephrine uptake inhibitor, and fluoxetine, a
      selective serotonin uptake inhibitor. The results indicated that low doses of
      desipramine and fluoxetine produced different behavioral patterns in the FST, but
      only after chronic administration. The results strengthen the validity of the FST
      as a behavioral screen for antidepressant drugs with features similar to an
      animal model of depression.

PMID- 9234046
TI  - Smoked heroin and cocaine base (speedball) combinations in rhesus monkeys.
AB  - The purpose of this investigation was to compare the self-administration of
      heroin and cocaine base, alone and in combination, in rhesus monkeys (Macaca
      mulatta) self-administering a combination of heroin (0.1 mg/kg/delivery) and
      cocaine base (1.0 mg/kg/delivery) via the smoking route. Smoke deliveries were
      contingent on completion of a chained fixed ratio (FR; lever press), FR 5
      (inhalation) schedule. The lever press FR values (64, 128, 256, 512, and 1024)
      represented increasing drug price. Demand functions (Consumption X price) were
      obtained for the heroin and cocaine combination and compared with previously
      determined demand functions for smoked heroin and cocaine alone. As the FR
      increased and the number of responses emitted increased, the number of drug
      deliveries decreased. The demand functions were not different for heroin versus
      cocaine alone or for the cocaine alone versus the cocaine-heroin combination.
      However, the demand for heroin alone was significantly less than the demand for
      the cocaine-heroin combination, suggesting that smoked cocaine base enhances the
      behavioral effects of smoked heroin.

PMID- 9234047
TI  - Ibogaine interferes with the establishment of amphetamine place preference
      learning.
AB  - The ability of ibogaine, injected 24 hr before amphetamine, to modify the
      establishment of amphetamine-induced place preference learning was assessed. A
      single injection of ibogaine blocked the establishment of amphetamine place
      preference after 1 or 2 conditioning trials, but it was less effective after 4
      trials. The reduced effectiveness of ibogaine across multiple conditioning trials
      appears to be the result of the development of tolerance to ibogaine.

PMID- 9234048
TI  - Multielemental stimulus control: effects of saccharin concentration on a
      discriminated morphine-saccharin taste aversion.
AB  - The effects of saccharin concentration on the stimulus control by a compound
      stimulus consisting of morphine, saccharin (0.01, 0.03, or 0.10%, wt/vol), and a
      ball bearing drinking nozzle in a discriminated taste aversion (DTA) procedure
      were examined in rats (Rattus norvegicus). In paired rats injections of lithium
      followed presentation of this compound stimulus, whereas in unpaired rats saline
      injections followed this stimulus. DTA acquisition was more rapid at higher
      saccharin concentrations. In testing with each individual stimulus element,
      stimulus control was clearly exerted by all 3 stimulus elements. When another
      stimulus element was presented jointly with saccharin, behavioral control was
      similar to that of saccharin alone. Behavioral control by saccharin increased
      with saccharin concentration. However, behavioral control by the 2 other stimulus
      elements was relatively unaffected when the saliency of the saccharin element was
      increased.

PMID- 9234049
TI  - Effects of d-amphetamine on task performance and social behavior of humans in a
      residential laboratory.
AB  - Six healthy adult male volunteers lived for 11 days in a residential laboratory.
      Acute effects of d-amphetamine (0, 5, or 10 mg/70 kg) on performance of tasks,
      social interaction, and self-reports of drug effects were measured. Each day,
      participants engaged in a 6.5-hr work period and a 6.5-hr recreation period.
      Beverages containing d-amphetamine or placebo were consumed daily before the work
      period and before the recreation period. d-Amphetamine increased response rate
      without affecting accuracy on some tasks. d-Amphetamine increased the proportion
      of time spent engaging in verbal interaction during the first but not the second
      week of study. No changes in self-reported drug effects were observed. Thus, d
      amphetamine improved performance in the absence of stimulant-like subjective
      effects. This differentiation between performance and subjective effects confirms
      the importance of determining the effects of drugs on a range of behaviors.

PMID- 9234050
TI  - Craving is associated with smoking relapse: findings from three prospective
      studies.
AB  - In a combined sample of more than 2600 smokers, immediate postcessation craving
      is shown to be prospectively associated with smokers' ability to maintain
      abstinence. Relapse is strikingly rapid among those reporting high levels of
      craving following cessation. More than 32% of those with high craving scores
      relapsed within 1 week of cessation. In contrast, fewer than 15% of those with
      low craving relapsed in the first week (p < .001). Our findings provide a warrant
      for an increased research effort designed to provide a better understanding of
      the factors that control following smoking cessation and the processes by which
      craving influences smoking relapse.

PMID- 9234051
TI  - Effects of lorazepam on the distribution of spatial attention.
AB  - Reaction time (RT) to stimulus events was assessed for 2 tasks with different
      spatial attention demands before and after receiving either a placebo or
      lorazepam (1 mg). In 1 task (onset), 12 participants responded to the onset of 1
      of 5 potential dot targets contained within either a small or large area. In the
      other task (offset), all 5 targets were illuminated and 12 participants responded
      to the offset of 1 of them. In the onset task, lorazepam slowed RT equally for
      both the large and small display areas. In the offset task, substantial
      impairment was found with the large but not the small display area. Results are
      consistent with the hypothesis that lorazepam interferes with the processes
      involved in the movement of spatial attention. The possibility that lorazepam
      selectively impairs the disengage component of attentional movement is discussed.

PMID- 9234052
TI  - Comparing self-reported cocaine use with repeated urine tests in outpatient
      cocaine abusers.
AB  - Sixty-one participants in outpatient therapy for cocaine dependence provided
      urine samples and self-reports of cocaine use 3 times a week for 4 weeks.
      Participants later gave a retrospective self-report of cocaine use for the month
      on the addiction Severity Index (ASI). Comparisons with urine test values
      revealed substantial underreporting of cocaine use on both measures, and results
      from the 2 forms of self-report were only imperfectly correlated. More
      participants admitted to at least 1 cocaine use episode on the ASI than on the
      repeated self-reports, but the repeated reports provided a more accurate index of
      the relative frequency of cocaine use during the month. Self-reports can enhance
      cocaine use detection when urines are infrequently collected and can help
      determine whether consecutive positive urine samples represent elevated
      metabolite levels from a single drug use episode. However, self-reports cannot
      substitute for regular urine sampling.

PMID- 9234053
TI  - Does the repeated gambles procedure measure impulsivity in social drinkers.
AB  - P. Sarfati and K. G. White (1991) found that heavy social drinkers were more risk
      averse than light drinkers in a repeated gambles procedure. Given a theoretical
      argument that risk aversion corresponds to impulsivity in this context, this
      result implied that heavy drinkers are more impulsive than light drinkers. The
      present study sought to replicate this finding, and, by administering
      questionnaire measures of impulsivity, to explore the relation between drinking
      and impulsivity as measured by the repeated gambles procedure and impulsivity as
      measured by questionnaires. Results showed more impulsivity among heavy drinkers
      than light drinkers on the questionnaires but not on choices during the repeated
      gambles procedure. These results question the utility of the repeated gambles
      procedure as a measure of impulsivity and as a useful vehicle for studying the
      drinking-impulsivity relation.

PMID- 9234054
TI  - Afterload mismatch-related problems after "domino" heart transplantation.
AB  - The heart transplants with domino technique, which uses donor hearts from heart
      lung recipients, increases the pool of donors, provides the advantage of
      shortening the ischemic time and makes suitable hearts for patients with
      pulmonary hypertension. The present study aimed to characterise the pre- and post
      transplant clinical and hemodynamic profiles of patients that underwent domino
      transplant in Pavia. METHODS: Between 1991 and 1992, 9 heart transplants were
      performed with the domino procedure at I.R.C.C.S. Policlinico S. Matteo of Pavia.
      Domino donors (6 with primary pulmonary hypertension, 2 with Eisenmenger's
      syndrome due to atrial septal defect, 1 with cystic fibrosis) underwent
      electrocardiographic, echocardiographic, chest roentgenogram studies, and right
      heart catheterization and coronary angiography (for donor older than 40). Domino
      recipients, 6 males and 3 females with a mean age of 44 years, had dilated
      cardiomyopathy (4 cases), coronary artery disease (4 cases) and valvular heart
      disease (1 case) (group 1). Seven of the 9 cases entered the study; 2 were
      excluded: one because had undergone heterotopic transplantation, the other had
      received the heart from another country and therefore the graft had suffered from
      a very long ischemic time. Controls group consisted of 12 patients who had
      consecutively undergone cardiac transplantation with non-domino donors during the
      same period (group 2). Immunosuppression was similar in both groups, and
      consisted of a combination of cyclosporin A, azathioprine and corticosteroids,
      plus a 7-day-course of antithymocyte globulin. Hemodynamic and echocardiographic
      controls were performed at 2, 3 and 4 weeks (short-term control) and at 2 and 6
      months (mid-term control) after surgery. RESULTS: Domino donors (39 +/- 12.5
      years) had significantly higher mean right ventricular end-diastolic diameter and
      lower left ventricular diameter than normal mean values. Domino recipients had
      significantly higher mean pulmonary arteriolar resistances than controls; mean
      ischemic time was also significantly lower in group 1 than in group 2. Short- and
      mid-term controls after surgery in group 1 showed persistently higher systemic
      vascular resistances and pulmonary vascular resistances and lower cardiac output
      than in group 1. Two patients developed an early and unexpected increase in
      pulmonary wedge pressure accompanied by severe paroxysmal nocturnal dyspnea and
      mitral regurgitation. In all cases, the left ventricles were relatively
      inadequate; the combination of low cardiac output and of high systemic vascular
      resistances favoured the occurrence of an afterload mismatch condition that was
      worsened by chronic hypoxia. This condition must be known and expected in these
      patients after transplantation in order to provide timely and effective treatment
      to potentially life-threatening left ventricular failure episodes. IN CONCLUSION,
      the subset of transplanted patients that receives domino donors may develop left
      side afterload mismatch which, combined with low cardiac output, with high
      systemic vascular resistances and with the effects of chronic hypoxia originally
      suffered by the heart, may cause sudden and unexpected left-side heart failure
      which has to be timely recognised and managed. Although hemodynamic adaptation of
      this patients is highly problematic, it does not limit the value of the domino
      procedure.

PMID- 9234055
TI  - Hemodynamics of "domino" heart transplantation. The role of ventriculo
      ventricular interaction and after load mismatch.

PMID- 9234056
TI  - Age limits for heart transplantation: medical aspects.
AB  - OBJECTIVE: To contribute to the analysis of the medical issue of aging as a
      selection criteria for heart transplantation (HT) METHODS: Elderly candidates (52
      subjects, aged > or = 60) were compared with younger patients (64 candidates,
      aged 50-55) in: clinical pattern (sex, etiology, duration of disease); laboratory
      and instrumental data (multiple organ function, hemodynamics, maximal and
      submaximal exercise capacity, nutritional status); follow-up (death,
      transplantation, status I, decompensation, complications) of at least 6 months.
      RESULTS: When compared with younger candidates, over 60 patients did not differ
      in clinical pattern, in all instrumental data, in end-organ function, in
      transplantation rate, in fatal and non-fatal cardiac events. In both groups the
      medical management was similarly complex. CONCLUSION: In regard to the medical
      issue, no reasons emerged to exclude older patients suitable from HT.

PMID- 9234057
TI  - Problems and pitfalls in evaluating studies for pacing in heart failure.
AB  - Pacing therapy has been recently proposed as a new non-pharmacological approach
      to patients suffering from congestive heart failure refractory to medical therapy
      (refractory CHF), but the extention and the real benefit of this method remains
      to be defined. Although pacing therapy for refractory CHF has been restricted to
      patients in sinus rhythm presenting atrial, atrioventricular or interventricular
      conduction disturbances, considerable conflicting results have been published.
      The contradictory data is most likely due to large heterogeneity of the
      investigated study population (ie etiology of CHF, NYHA class, duration of follow
      up, end-points of the study, etc.), to difference in study methology as well as
      in the site and modality of acute and chronic pacing. Although several empirical
      data indicates, at least in some individuals, major improvement in CHF symptoms
      by properly coordinating the atria and the ventricles thus reducing pre-systolic
      mitral and/or tricuspidal regurgitation or finally, prolonging the diastolic
      filling time, a lack of understanding of the mechanisms responsible for acute and
      chronic benefit persists. In evaluating pacemaker therapy as a new supportive
      treatment for CHF, the clinical investigator must consider that each study
      protocol embodies assumptions and methodological limitations and thus provides an
      incomplete analysis of potential benefit. Relying solely on noninvasive measures
      is risky due to problems of sensitivity and repeatability.

PMID- 9234058
TI  - Management strategies of patients with severe congestive heart failure. Current
      limited goals versus future definitive solutions.

PMID- 9234059
TI  - Three-dimensional analysis of normal regurgitant jets in a St. Jude Medical
      mitral prosthesis.

PMID- 9234060
TI  - New flow cytometric technologies for the 21st century.
AB  - The envelope that defines the limits within which flow cytometry was developed is
      being rapidly expanded. For example: detection sensitivity has been extended to
      single molecules, the size range of "particle" analysis now extends from DNA
      fragments to plankton (1,000.+ microns), cell and chromosome sorting rates are
      being increased dramatically by using inactivation procedures (50,000 per second
      versus 2,000 per second), rapid kinetic flow cytometry enables real-time analysis
      of molecular assembly and cell function in the sub-second time domain, the
      lifetime of a fluorochrome bound to a single cell can be measured with nsec
      precision, and classical karyotype information (cell to cell heterogeneity) can
      be determined in a flow based system. These frontiers have greatly expanded the
      range of new and exciting flow cytometric based biomedical applications. New
      enabling technologies have provided the means to measure DNA cleavage by the
      structure-specific nuclease, human Flap Endonuclease (FEN-1), in the 300 msec
      time frame. Phase sensitive measurements and fluorescence lifetime are proving to
      be major advances for understanding molecular environments that change with, for
      example, the process of apoptosis. The ability to detect single fluorescent
      molecules has been applied to the analysis of DNA fragments obtained from
      enzymatic digestion of lambda DNA. This technology is being used to rapidly and
      very accurately size DNA fragments for the human genome project. Optical
      chromosome selection is a faster, better, less complex approach to chromosome
      sorting. This method is based on the induction of specific damage to the DNA of
      selected chromosomes. Lastly, the miniaturization of a single cell fractionator
      has made it possible to perform single cell flow cytogenetics.

PMID- 9234062
TI  - Ultrastructure of the human egg.
AB  - This report on the fine structure of human oocyte is based on 20 years research
      where over 2000 eggs were examined by TEM in conjunction with our research on
      various methods of assisted reproduction. The eggs were routinely fixed in
      glutaraldehyde/osmium tetroxide, flat embedded in araldite, serially sectioned
      and examined by TEM. The oocytes were usually recovered after gonadotrophin
      stimulation. The general organisation of the mature human oocyte conforms to that
      of other mammals but has some unique features. The oocyte has the basic cell
      organelles such as mitochondria, lysosomes, two types of smooth endoplasmic
      reticulum (SER)-vesicular and tubular aggregates, multivesicular residual bodies,
      lipofuschin, microfilaments and microtubules. Golgi, RER and ribosomes are very
      rare and the egg has no yolk. It's surface has few microvilli, pinocytolic
      caveolae and 1-3 layers of cortical granules. The zona pellucida is composed of
      fine fibrils and granules embedded in an amorphous matrix and encloses a
      perivitelline space containing polar bodies. Remnants of corona cell junctions
      may be found at the oolemma. The metaphase II spindle is often oriented
      perpendicular to the surface and is barrel-shaped, anastral and lacks centrioles.
      Osmiophilic centrosomes are not demonstrable in human eggs since the maternal
      centrosome is inactive. The sperm centrosome organizes mitotic spindles of the
      embryo after fertilization, whereas in mice the maternal centrosome is active and
      dominant during cleavage. The stages of peri-ovulatory maturation and differences
      in oocyte structure during maturation are also presented. Oocytes ageing in
      culture show progressive swelling of vesicular SER culminating in vacuolation,
      denser mitochondria (clouding together or associated with vacuoles) peripheral
      conglomerations or centripetal migration of cortical granules and increased
      lysosomal activity. Prolonged culture also causes displacement and
      disorganisation of metaphase II spindles, loss of microtubules and consequent
      displacement of chromosomes. Evidently the cytoskeleton becomes disorganized.
      Some observations on oocyte maturation in vitro and spontaneous activation of
      oocytes are included.

PMID- 9234061
TI  - [Quality control and cytogenetic analysis of human pre-embryos fertilized and
      cultured in vitro].
AB  - For the purpose to evaluate in vitro culture conditions of human preembryos, the
      efficacy of conventional culture and co-culture systems on embryonic development
      and genetic disorders was studied. Firstly, the development of cultured mouse
      embryos grown in standard media (Whitten's, GPM, HFT and Ham F10) or in HFT
      medium with different helper cell layers was compared. Embryonic growth was
      substantially reduced during in vitro culture, demonstrably by impaired cell
      proliferation, compared with in vivo controls. In in vitro fertilization and
      culture condition, SCEs of blastocysts were significantly increased. Development
      in co-culture with the feeder layers was notably better than in standard media.
      These results suggest that human preembryos could be rescued by the use of helper
      cells. Increased developmental rates and the cell numbers of blastocysts were the
      most evident morphological features of human preembryos that developed in co
      culture with uterine luminal epithelial cells. However mosaicism may be caused by
      in vitro culture conditions and its onset may indicate when a disturbance in the
      embryonic development has occurred. It is advisable to perform further research
      into the mechanism of feeder cell-embryo interaction for understanding the
      optimal conditions of embryonic development in vitro.

PMID- 9234063
TI  - [Human embryo cryopreservation].
AB  - Widespread incorporation of human embryo cryopreservation into in-vitro
      fertilization (IVF) programs may reduce the risk of multiple gestation and severe
      ovarian hyperstimulation syndrome while contributing to an overall increase in
      pregnancy rates. The main known complication arising from ovarian stimulation is
      ovarian hyperstimulation syndrome (OHSS). The development of severe OHSS is
      contingent on either exogenous administration of hCG or endogenous pregnancy
      derived hCG stimulation. The rationale behind the strategy of electively
      cryopreserving all embryos from woman at risk of developing OHSS is therefore to
      avoid these additional influences of the exogenous and trophoblastic HCG upon the
      ovary. Successful implantation depends on embryo quality and uterine receptivity.
      If a good embryo was present, among those in the cleavage stage, the pregnancy
      rate was significantly higher (41.5%) after the transfer of embryos at the 3
      approximately 4 cell stage in the cases of pronuclear-stage freezing. A
      significantly higher pregnancy rate of multilayered echogenic patterns was
      observed when pregnancy and nonpregnancy cycles were compared. No differences in
      mean endometrial thickness were observed when pregnancy and non pregnancy cycles
      were compared. No pregnancies occurred when endometrial thickness was less than 5
      millimeters. A statistically significant decrease in pregnancy rate was seen when
      thawed embryo transfer is performed in a natural cycle in patients who were 35 to
      39 years old. No age-related decline was seen in patients in which transfer was
      performed in the hormone replacement cycle.

PMID- 9234064
TI  - Human mesenchymal stem cells respond to fibroblast growth factors.
AB  - Human mesenchymal stem cells can be isolated from bone marrow aspirates, purified
      and cultured for many passages without losing their unique properties. One of the
      hallmarks of stem cells is pluripotency, and human mesenchymal stem cells can be
      induced to assume phenotypes of mesenchymal tissues including, but not limited
      to, those of osteocytes, chondrocytes and adipocytes. Due to their ability to
      form cartilage, bone, fat and other connective tissue, human mesenchymal stem
      cells have great potential in regenerating diseased or injured tissues.
      Successful growth of human mesenchymal stem cells is essential to this process,
      and we have examined the response of human mesenchymal stem cells towards FGF1
      and FGF2, two potent growth factors for human tissues. We provide evidence that:
      1) human mesenchymal stem cells produce mRNA for receptors for FGF1 and FGF2; 2)
      these receptors can be detected on the surface of human mesenchymal stem cells;
      3) FGF1 and FGF2 increase the rate at which human mesenchymal stem cells
      proliferate.

PMID- 9234065
TI  - [Stem cell-fed maturational lineages and epithelial organogenesis].
AB  - Stem cell-fed maturational lineages have long known to exist in rapidly
      proliferating tissues such as bone marrow, gut and epidermis. Recent studies
      support the hypothesis that stem cell-fed maturational lineages occur also in
      quiescent tissues. In this review is presented evidence for this hypothesis using
      liver as one of the model systems representative of quiescent tissues. In
      addition, studies are summarized indicating that control of growth and tissue
      specific gene expression is dependent on maturational lineage mechanisms
      operating dynamically and sometimes synergistically in combination with gradients
      of regulatory signals that include hormones, growth factors and extracellular
      matrix components. Tissue engineering for optimal maintenance of cells and
      tissues ex vivo and for the development of bioartificial organs will depend on
      use of cells at specific maturational lineage stages, seeding them onto substrata
      of specific mixtures of extracellular matrix components, and culturing them in
      hormonally and nutritionally defined media.

PMID- 9234066
TI  - [Regulation of growth and survival of germ cells].
AB  - Growth and survival of germ cells seem to be strictly regulated by a number of
      environmental and intrinsic factors. One of the most important factor is Steel
      factor, which is necessary not only for the rapid proliferation and survival of
      primordial germ cells(PGCs) in embryos, but also for the development of
      spermatogonia and oocytes in adult gonads. Other growth factors which are linked
      to different signaling pathway collaboratively support PGC growth with Stecl
      factor. Therefore, synergistic action of different signal transduction pathway
      seems to be important for PGC growth. In adult testis, a large part of
      spermatogonia undergoes cell death, but the physiological significance and
      molecular mechanisms of this process are largely unknown. We have investigated
      the effect of misexpressing Bcl-2 in spermatogonia in transgenic mice. And we
      found that ectopically expressed Bcl-2 in spermatogonia inhibited their normal
      apoptosis. In addition abnormally accumulated spermatogonia fail to undergo
      further differentiation and survival, and they were just deleted from testis.
      These results indicate that spermatogonial apoptosis is part of the normal
      program of mammalian spermatogenesis and is regulated by a pathway affected by
      Bcl-2.

PMID- 9234067
TI  - Methioninase: a therapeutic for diseases related to altered methionine metabolism
      and transmethylation: cancer, heart disease, obesity, aging, and Parkinson's
      disease.
AB  - Methionine metabolism and transmethylation are central to the metabolism and
      differentiation of all known cells. In enkaryotic organisms, methionine
      metabolism and transmethylation are of paramount importance in modification and
      regulation of proteins, lipids, and nucleic acids. The differential methylation
      of genes regulates their expression in the myriad of cells in eukaryotic
      organisms. Disruption and abnormalities in methionine metabolism and
      transmethylation seems to be associated with the major diseases of mankind,
      including cancer, heart disease, aging, obesity, and Parkinson's disease. In this
      review, we describe how aberrant and abnormal methionine metabolism and
      transmethylation are related to these major diseases. Most importantly, we review
      and hypothesize how the developing therapeutic recombination methioninase
      (rMETase) can be utilized to cure or prevent all of these diseases.

PMID- 9234068
TI  - Treatment of cancer using pulsed electric field in combination with
      chemotherapeutic agents or genes.
AB  - Electroporation is a standard laboratory technique originally developed for in
      vitro transfer of molecules into cells. It involves application of electrical
      pulses ranging from micro- to milliseconds that create transient pores in the
      cell membrane allowing intracellular access of exogenous molecules. This
      technique has been successfully applied to regress tumors in animal models by
      combining electroporation with chemotherapeutic agents--a process known as
      electrochemotherapy (ECT) which substantially enhance cytotoxicity of some
      antineoplastic agents. Recently ECT has moved into clinical arena and patients
      with cutaneous tumors and head and neck cancers have been treated very
      effectively with ECT. Parallel to ECT, a technique has also been developed which
      makes it possible to inject plasmid DNA and combine it with in vivo
      electroporation--electro--genetherapy (EGT)--to deliver in a highly efficient
      manner both marker and functional genes into target tissue and achieve gene
      expression. Thus, in vivo electroporation is contributing to the development of a
      new strategy for cancer treatment with both drugs and genes.

PMID- 9234069
TI  - Enhancement of chemotherapeutic effects with focused shock waves: extracorporeal
      shock wave chemotherapy (ESWC).
AB  - The effects of shock waves in combination with various anti-cancer agents i.e.
      Bleomycin(BLM), Cis-platinum (CDDP) and 5-fluorouracil(5-FU) on various human
      cancer cells were examined. It was only with BLM that enhancement was evident in
      all cell lines. The degree of chemotherapeutic enhancement was proportional to
      the amount of shock wave energy applied. Ladder formation of DNA in GCIY, a
      gastric cell line, was observed only when treated with both BLM and shock waves
      in combination. When SW 480, a colon cancer cell line, transplanted into the back
      of nude mice were treated with a combination of i.v. injected BLM and regional
      exposure to shock waves, a significant enhancement of chemotherapeutic effects
      was observed in terms of the tumor growth curve. When cancer cells exposed to
      shock waves and observed under scanning and transmission electron microscopes,
      microvilli on the cell surface disappeared and numerous dimples(diameters
      distributed from 0.05 to 0.5 microns) became apparent. These dimples were
      concluded to be pores penetrating through the cell membrane, because reagents
      such as propidium iodide or 5(6)-carboxyfluorescein could enter cells treated
      shock waves.

PMID- 9234070
TI  - Synergistic antitumor effects of human interferon-beta and interferon-gamma on
      human gastric adenocarcinoma cells.
AB  - The combined effects of different classes of interferon (IFN) on human gastric
      adenocarcinoma cell line HPE-GAC-2 (GAC-2) were investigated in vitro.
      Synergistic effects of IFN-beta and -gamma, causing cell death, were observed in
      a dose-dependent manner. IFN-gamma modulated the sensitivity of GAC-2 cells to
      the cytocidal effect of IFN-gamma. The modulatory effect was independent of the
      cytostatic or cytocidal activity of IFN-beta since brief contact with IFN-beta
      did not influence the growth kinetics of the cells and was effective in modulate
      the cellular sensitivity to IFN-gamma. A brief pretreatment of the cells with IFN
      alpha or-beta resulted in a variable level of modulation, whereas coculture of
      the cells with IFN-beta or -alpha and IFN-gamma had a similar cytotoxic effect
      indicating a different level of activity induced by IFN-alpha and -beta with the
      common type I receptor. These results suggest that IFN-beta-induced modulation
      was receptor-mediated. Phase contrast microscopy showed evidence of apoptotic
      cell death induced by one or more IFN agents. The morphological changes included
      chromatin condensation and nuclear fragmentation which were apparent at as early
      as 6 hr of culture with a high concentration of IFN(s). Our results indicate that
      IFN-beta and IFN-alpha enhance the in vitro apoptotic effects of IFN-gamma
      against GAC-2 tumor cells.

PMID- 9234071
TI  - Establishment and characterization of a new human glioblastoma cell line (MGM-1)
      with highly motile phenotype.
AB  - A new cell line MGM-1 was established from a primary tumor of the left temporal
      lobe with histological diagnosis of glioblastoma multiforme, removed from a 64
      year-old Japanese male. The patient died of recurrence and unusual extracranial
      metastases of the tumor 7 months after the surgery. The cultured MGM-1 cells are
      spindle or polygonal in shape. After serial passages, glial fibrillary acidic
      protein became negative immunocytochemically in vitro. The modal chromosome
      number was 61-64. Doubling time and soft agar colony forming efficiency were
      42.9h and 0.4%, respectively (at 25th passage). MGM-1 is a highly motile cell
      line in vitro and its serum-free conditioned medium is chemotactic and
      chemokinetic for other glioma cells. Secretion of gelatinases (probably MMP-2/72
      kDa type i.v. collagenase) and MMP-9/92-kDa type i.v. collagenase) and urokinase
      type plasminogen activator were also investigated. MGM-1 would therefore be
      useful for studying the mechanisms regulating glioma-cell motility and invasion.
      The MGM-1 cell line has been propagated continuously by serial passages (more
      than 100 passages) during the past 4 years.

PMID- 9234073
TI  - Improving chest pain evaluation within a multihospital network by the use of
      emergency department observation units.
AB  - BACKGROUND: Since 1993 the 13 VHA Southern New England (VHA-SNE) hospitals have
      been engaged in a regionally sponsored initiative to analyze and improve selected
      clinical processes. Nine of these hospitals have chosen to participate in an
      initiative in which observation units were postulated to offer a tool for
      improving the care of patients with chest pain-the VHA initiative to Implement
      Chest Pain Treatment in Observation Units. THE FIVE PHASES: In phase 1 of the
      initiative, the VHA-SNE's Clinical Benchmarking Work Group reviewed the medical
      literature, which confirmed longstanding systemic and pervasive problems in the
      evaluation of chest pain patients. The work group's preferred practice was the
      outpatient "rule out myocardial infarction [MI] evaluation" program during
      monitored observation; serial testing can accurately diagnose low- and moderate
      probability patients with MI. In Phase 2 the study group surveyed the emergency
      departments in the nine hospitals, discovering significant variation in admission
      rates and practice patterns. During phase 3 the work group identified a health
      care organization demonstrating best-practice performance--one of the few
      hospitals in the nation with an operational outpatient "rule out MI evaluation"
      program. A team site-visited that organization and recorded information about its
      structure and processes. VHA-SNE then published a monograph that identified its
      current performance, described the best-practice approach, offered strategies to
      implement the model program, and analyzed the financial implications and return
      on investment. In phase 4 a pilot hospital implemented the model program, which
      in phase 5 is being extended to the other hospitals represented in the work
      group. Information regarding protocols, lessons learned, and barriers to
      implementation was freely provided.

PMID- 9234072
TI  - The quality improvement ratio: a method to identify changes in screening rates.
AB  - BACKGROUND: Because many managed care organizations are using HEDIS (Health Plan
      Employer Data and Information Set) and other measurement sets for their report
      cards, these measurements are also used in improvement projects to show changes
      over time. One analytic strategy is to compare measurements between one period
      and another after an intervention has been made. Such an analysis, which is
      termed here the "conventional" or "two-group analysis" and which would use either
      a Chi-square test or Fisher's exact test, entails three problems. The
      conventional analysis is not statistically valid because there are members in
      common in the two groups; population changes can affect the conventional analysis
      and confound the identification of any change with time; and members who do not
      change their behavior obscure the changes that are occurring in the conventional
      analysis. METHODS: The Quality Improvement Ratio (QuIR) does not suffer from
      those limitations; it is calculated only from members who change status. For
      example, in evaluating the effectiveness of an intervention to improve preventive
      health screening, the QuIR is calculated only from members becoming screened in
      the second period after being unscreened in the first period, or vice versa. The
      QuIR is the ratio of the number of members becoming screened in the second period
      divided by the number becoming unscreened. Methods to test the statistical
      significance of the QuIR are based on the standard test for paired binary data,
      McNemar's test. CONCLUSION: Whereas the conventional approach addresses whether
      there are differences in rates between periods, and analysis using the QuIR
      focuses directly on whether the rates are different because of an intervention.

PMID- 9234074
TI  - Medical record review as a measure of the effectiveness of organ procurement
      practices in the hospital.
AB  - Organ procurement efforts are central to the transplant sector of the health care
      system, yet procurement effectiveness is not routinely assessed. MRRs provide a
      solid foundation for identifying gaps in organ procurement performance,
      implementing and tracking the success of QI initiatives, and monitoring ongoing
      performance.

PMID- 9234075
TI  - An invitational workshop on collaboration between quality improvement
      organizations and business coalitions.
AB  - BACKGROUND: The center for Clinical Quality Evaluation, in conjunction with The
      American Health Quality Association, Midwest Business Group on Health, National
      Business Coalition on Health, and the funder, the Agency for Health Care Policy
      and Research, conducted an invitational workshop January 14-15, 1997, in
      Washington, DC. A select group of federally designated peer review/quality
      improvement organizations (QIOs)--organizations that work at the local level to
      improve and promote the health status of Medicaid and Medicare beneficiaries--and
      business coalitions from nine states met to discuss public/private collaboration
      on community-based quality improvement projects. WORKSHOP AGENDA: The 1 1/2-day
      sessions included a keynote address by Chris Queram, MA, chief executive officer
      of the Employer Health Care Alliance, Madison, Wisconsin, who provided background
      and context on the principles of community-based collaboration; a presentation on
      an advanced QIO/business coalition collaborative case study by HealthInsight, Inc
      (the Utah QIO), and Business/Health Partnership (the Salt Lake City business
      coalition); a case study on a beginning QIO/business coalition collaborated by
      the Health Accountability Foundation, a partnership between IPRO (the New York
      State QIO) and the New York Business Group on Health (the New York City business
      coalition); small group breakout sessions, where participants from each
      state/local community and Washington, DC-based health associations and specialty
      societies met to identify common goals and opportunities to collaborate; report
      on the progress made by each small group; and discuss future plans for
      collaborating on quality improvement projects. CONCLUSIONS: Many of the
      participating QIOs and business coalitions have already begun collaborating on
      quality improvement projects.

PMID- 9234076
TI  - Mechanisms of electrical field stimulation-induced vasodilatation in the guinea
      pig basilar artery: the role of endothelium.
AB  - 1. The role of endothelium in neuronal vasodilatation elicited by electrical
      field stimulation (EFS) was investigated in preparations of the isolated guinea
      pig basilar artery in which the tone was raised with prostaglandin F2 alpha. 2.
      In preparations with intact endothelium, EFS produced frequency-dependent
      dilatations which were not affected by guanethidine but were slightly yet
      significantly reduced by atropine (1 microM), and were blocked by tetrodotoxin (1
      microM) and the nitric oxide synthase inhibitor L-NAME (10 microM). 3.
      Dilatations were elicited by acetylcholine (3 microM); these were blocked by L
      NAME and atropine (1 microM). 4. Dilatations were elicited by nicotine (100
      microM); these were blocked by L-NAME and hexamethonium (100 microM). 5. Dilation
      elicited by sodium nitroprusside (SNP, 3 microM) was not affected by L-NAME. 6.
      The inhibitory effects of L-NAME were partially prevented by L-arginine (1
      microM). 7. Removal of the endothelium resulted in a significant reduction of
      dilatations elicited by EFS, elimination of the dilator action of acetylcholine,
      but enhancement of that to SNP. 8. The results suggest that EFS-induced
      vasodilatation is mediated in part by the nitrergic transmitter and in part
      endothelium derived relaxing factor (EDRF) activated by acetylcholine released
      from cholinergic nerves.

PMID- 9234077
TI  - Acetylcholinesterase histochemistry and functional characterization of the
      muscarinic receptor mediating the contraction of the bovine oesophageal groove.
AB  - 1. By using acetylcholinesterase (AChE) histochemistry and in vitro isometric
      techniques, we have studied the presence and distribution of AChE-positive
      nerves, as well as the effects of muscarinic cholinoceptor agonists and selective
      antagonists, in the bovine oesophageal groove. 2. AChE-positive nerves and cells
      were distributed widely on the oesophageal groove floor. These fibres originated
      from adventitial ganglia containing bodies with high AChE activity and were shown
      grouped as large adventitial nerve bundles. 3. Both in the presence and absence
      of physostigmine, acetylcholine (ACh) induced concentration dependent
      contractions of bovine oesophageal groove strips. The rank order of the pD2
      values for muscarinic agonists was: oxotremorine-M (7.37) = carbachol (7.14) >
      acetylcholine plus physostigmine (6.46) > bethanechol (5.42) > McN-A-343 (4.45) >
      acetylcholine (4.06). 4. Hexamethonium (10(-6)-10(-4) M), a nicotine receptor
      blocker, did not affect the carbachol concentration-response curve, which was
      significantly inhibited by the muscarinic antagonist, atropine (10(-9)-10(-8) M).
      5. The preferential muscarinic antagonists pirenzepine (M1), 11-(2(diethyl
      amino)methyl)-1- piperidinylacetyl)-5,-11-dihydro-6H-pyrido(2,3-b)-(1,4)
      benzodiaze pine-6-one (AF-DX 116) and methoctramine (M2), 4-diphenyl-acetoxy-N
      methyl-piperidine methiodide (4-DAMP) and p-fluorohexahydrosiladiphenidol (p-F
      HHSiD) (M3) evoked rightwards displacements in a parallel manner of the carbachol
      control curve, and there was no decrease of the maximum response with the highest
      concentration of antagonist utilized. The muscarinic antagonist affinities,
      expressed in terms of pA2, values, were: atropine (9.51) = 4-DAMP (9.32) > p-F
      HHSiD (7.78) > tropicamide (7.40) > pirenzepine (6.91) = AF-DX 116 (6.88) =
      methoctramine (6.71). This muscarinic antagonist profile suggests that an M3
      receptor is involved in the carbachol induced contraction. 6. The present results
      suggest that a rich network of AChE- positive fibres is present in the
      oesophageal groove floor, where they form a nerve trunk and thinner branches
      accompanying blood vessels and sometimes around ganglia. The muscarinic
      cholinergic contraction of the bovine oesophageal groove seems to be mediated via
      activation of an M3 postsynaptic muscarinic receptor.

PMID- 9234078
TI  - Cardiac vagal effects of rilmenidine in the dog: comparison with clonidine.
AB  - 1. The cardiac vagal effects of rilmenidine (5 micrograms kg-1 min-1) and
      clonidine (0.5 micrograms kg-1 min-1) were studied in chloralose anaesthetized
      dogs. 2. Rilmenidine and clonidine progressively reduced the vagal stimulation
      induced bradycardia. As indicated by the ED70, rilmenidine was about 23 times
      less potent than clonidine in this respect. Concomitantly, both drugs dose
      relatedly decreased heart rate and mean blood pressure with potency ratios of
      rilmenidne to clonidine of about 1:23 and 1:12, respectively. 3. Importantly, the
      heart rate values observed under vagal stimulation during drug infusion never
      exceeded the values under basal vagal stimulation, and with both drugs large
      interindividual variations occurred under vagal stimulation. 4. These results
      show that the vagal bradycardia inhibition produced by rilmenidine and clonidine
      results from their true bradycardic effects and not from actual cardiac vagolytic
      properties.

PMID- 9234079
TI  - Different effect of anticholinergic agents and potassium channel openers on
      urinary bladder response to pelvic nerve stimulation in anaesthetized dogs.
AB  - 1. Effects of the anticholinergic agents atropine, oxybutynin, and terodiline,
      and the potassium channel openers YM934 (2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H
      1,4-benzoxazin-4-yl) pyridine N-oxide) and cromakalim were examined on urinary
      bladder response to pelvic nerve stimulation in pentobarbital-anaesthetized dogs.
      2. Pelvic nerve stimulation (PNS) produced a frequency-dependent increase in
      intravesical pressure in anaesthetized dogs. The response to PNS was abolished by
      topical tetrodotoxin, and markedly inhibited by intravenous hexamethonium,
      suggesting a neurogenic origin for the in vivo contractile response. 3. Atropine
      (0.3-3 mg kg-1 i.v.) and the anti-neurogenic bladder agents, oxybutynin (1-10 mg
      kg-1 i.v.) and terodiline (1-10 mg kg-1 i.v.) dose-dependently decreased the
      amplitude of the peak intravesical pressure response to PNS. At either frequency
      of PNS, these agents inhibited the response to a similar degree. 4. The potassium
      channel openers YM934 (1-10 micrograms kg-1 i.v.) and cromakalim (3-30 micrograms
      kg-1 i.v.) dose-dependently decreased the amplitude of the peak intravesical
      pressure response to PNS. The inhibitory effects of these drugs were more potent
      at lower than at higher frequencies of PNS. 5. These data suggest that the
      inhibitory effects of potassium channel openers on urinary bladder response to
      PNS are different from those of anticholinergic agents. The preferential
      inhibitory effect of potassium channel openers on detrusor smooth muscle
      contraction at lower frequencies of PNS may represent new potential for the
      treatment of neurogenic bladder.

PMID- 9234080
TI  - Profiles of the response to noradrenaline in the whole and bisected rat vas
      deferens.
AB  - 1. The present study was carried out to look at the differences between the whole
      and bisected rat vas deferens in response to cumulative and non-cumulative
      administration of noradrenaline in terms of sensitivity and maximum response. An
      effort was made to quantify the parameters characterizing the various components
      of the mechanical response to single concentrations of the agonist. 2. The
      sensitivity, as measured by the -log EC50 value for noradrenaline, was
      significantly lower in the prostatic portion than in the whole vas deferens and
      epididymal portion. The maximum contractions reached by the epididymal and the
      prostatic half were 65.03 +/- 10.43% and 13.84 +/- 5.28% of the maximal
      contraction evoked by noradrenaline in the whole rat vas deferens. 3. Various
      concentrations of noradrenaline were tested as single concentrations in the three
      preparations. These components of the response to noradrenaline were
      individualized, i.e. an early rapid phasic component followed by a second slower
      tonic component with spikes superimposed. The time-course of these components, as
      well as their ratios, were different depending on the concentration of agonist
      tested and on which half of the vas deferens was considered. 4. The importance of
      oxidation of exogenous noradrenaline as well of the neuronal and extraneuronal
      uptake mechanisms was considered. EDTA was devoid of any action. Cocaine enhanced
      potency and the maximum contraction of noradrenaline and all the parameters
      related to the different phases of the contraction were increased. Hydrocortisone
      at the highest concentration employed (2 X 10-5 M) was able to reduce
      significantly the -log EC50 value of the cumulative concentration-response curve
      to noradrenaline and both the phasic and tonic components of the contradiction to
      noradrenaline (3 X 10-6 M). 5. In conclusion, our evaluation of the parameters of
      the mechanical response of the whole and bisected vas deferens to noradrenaline
      rationalize the, often contradictory, findings of the current literature.
      Chiefly, the attainment of a careful description of the features of the response
      to noradrenaline can offer a dependable approach to the study of the underlying
      mechanisms of the three components.

PMID- 9234081
TI  - The peripheral NK-1/NK-2 receptor antagonist MDL 105,172A inhibits tachykinin
      mediated respiratory effects in guinea-pigs.
AB  - 1. Stimulation of sensory nerves causes release of tachykinins, including
      substance P (SP) and neurokinin A (NKA), which produce a variety of respiratory
      effects via NK-1 and NK-2 receptors, respectively. Hence, development of a
      compound which could potently and equivalently antagonize both receptors was
      pursued. 2. MDL 105,172A ((R)-1-[3-(3,4-dicholorophenyl)-1-(3,4,5
      trimethoxybenzoyl)- 3-pyrrolidinyl]-4- phenyl-piperidine-4-morpholinecarboxamide)
      exhibited high affinity for NK-1 (4.34 nM) and NK-2 (2.05 nM) receptors. In
      vitro, the compound antagonized SP (pA2 = 8.36) or NKA (pA2 = 8.61)-induced
      inositol phosphate accumulation in tachykinin monoreceptor cell lines. 3. In
      anaesthetized guinea-pigs, MDL 105,172A inhibited SP-induced plasma protein
      extravasation (ED50 = 1 mg kg-1, i.v.) and [beta-Ala8]NKA 4-10-induced
      bronchoconstriction (ED50 = 0.5 mg kg-1, i.v.) indicating NK-1 and NK-2
      antagonism, respectively. 4. Capsaicin was used to elicit respiratory effects in
      anaesthetized and conscious guinea-pigs; the latter were inhibited by MDL
      105,172A following i.v. (ED50 = 1 mg kg-1) or oral (ED50 = 20 mg kg-1)
      administration. Hence, MDL 105,172A can inhibit pulmonary responses to
      tachykinins released endogenously in the airways. 5. At doses up to 200 mg kg-1,
      p.o., MDL 105,172A failed to inhibit repetitive hind paw tapping induced by i.c.v
      GR 73632, and NK-1 selective agonist, in gerbils, whereas CP-99,994 (0.87 mg kg
      1, s.c.) completely ablated the effect. These data suggest that MDL 105,172A does
      not penetrate the central nervous system (CNS) and its tachykinin antagonism is
      restricted to the periphery. 6. MDL 105,172A is a non-peptide, potent, equivalent
      antagonist of NK-1 and NK-2 receptors. Its ability to inhibit both exogenously
      administered as well as endogenously released tachykinins support its use in
      examining the role of sensory neuropeptides in diseases associated with
      neurogenic inflammation including asthma.

PMID- 9234082
TI  - Calcitonin gene-related peptide (CGRP)-evoked inotropism during hyper- and hypo
      sensory-motor innervation in rat atria.
AB  - 1. Positive inotropic responses to calcitonin gene-related peptide (CGRP) were
      evaluated in atria isolated from in vivo rat models of hyper-sensory-motor
      innervation (following neonatal guanethidine treatment) and hypo-sensory-motor
      innervation (following neonatal capsaicin treatment), to explore the hypothesis
      that functional responsiveness of atrial myocardium to CGRP may correlate with
      tissue levels of the sensory-motor neurotransmitters. Comparative of inotropic
      responses to CGRP following in vitro treatment of atria with guanethidine was
      also performed. 2. Following long-term guanethidine treatment, positive inotropic
      responses to CGRP were significantly attenuated, while supersensitivity to the
      sympathetic transmitter noradrenaline was shown. Maximal inotropic responses to
      CGRP (30 nM) were 214.0 +/- 28.1 (n = 8) and 146.8 +/- 21.7 mg (n = 8; P < 0.01)
      increase of the basal contractile tension in control and treated preparations,
      respectively. The pD2 values for noradrenaline were 6.71 +/- 0.12 (n = 8) and
      7.26 +/- 0.13 (n = 6; P < 0.01) in control and treated atria, respectively. Acute
      application of guanethidine in vitro did not modify the positive inotropism by
      CGRP or the beta-adrenoceptor agonist isoprenaline. 3. Sensory-motor
      hypoinnervation following chronic treatment with capsaicin did not affect the
      inotropic responses to CGRP. Neither guanethidine nor capsaicin treatment
      affected the contractile apparatus of myocytes, as demonstrated by similar basal
      contractile tension as well as calcium-evoked inotropic responses in control and
      treated preparations. 4. In summary, increased sensory-motor innervation,
      following long-term sympathectomy with guanethidine, resulted in attenuation of
      the inotropic responses of the rat atrium to CGRP, while no changes in the
      inotropic responses were seen following sensory-motor denervation with capsaicin.
      Down-regulation of CGRP receptors or altered post-receptor signalling may be
      involved in the reduced responsiveness to CGRP.

PMID- 9234083
TI  - Adrenergic and nitrergic responses of the rat isolated anococcygeus muscle to a
      new toxin (makatoxin I) from the venom of the scorpion Buthus martensi Karsch.
AB  - 1. Makatoxin I (MkTx I) is a new toxin purified from the venom of the scorpion
      Buthus martensi Karsch. Contractile (excitatory, adrenergic) and relaxant
      (inhibitory, nitrergic) responses of the rat isolated anococcygeus muscle (Acm)
      to MkTx I were investigated. 2. MkTx I (0.28 microM) produced a rapid and very
      marked rise in the tone of the Acm which then gradually wanted to the control
      baseline. Phentolamine (5 microM), guanethidine (5 microM), tetrodotoxin (2
      microM) and reserpine pretreatment in vivo (5 mg kg-1 s.c. at 24 hr and 5 mg kg-1
      i.p. at 3 h) completely blocked the contractile responses of the Acm to MkTx I.
      The responses to noradrenaline (NA) were blocked by phentolamine, but were
      potentiated by guanethidine. 3. MkTx I (0.28 microM) also marked and rapidly
      relaxed the tone of the carbachol (CCh; 3 microM), precontracted Acm. The
      addition of sodium nitroprusside (SNP; 1 microM) also produced a marked and rapid
      relaxation of the Acm. TTx (2 microM) or NG-nitro-L-arginine methylester (L-NAME,
      50 microM) markedly inhibited the relaxant responses of the Acm to field
      stimulation (FS) as well as to MkTx I, but not the responses to SNP. 4.
      Therefore, the contractile responses of the rat anococcygeus muscle to MkTx I can
      be attributed to the release of transmitter NA on postjunctional alpha
      adrenoceptors, whereas the relaxant responses of the Acm to MkTx I involve the
      release of nitric oxide as the neurotransmitter which, presumably, results in the
      activation of the enzyme guanylate cyclase leading to relaxation of the muscle.

PMID- 9234084
TI  - The response of anesthetic agent monitors to trifluoromethane warns of the
      presence of carbon monoxide from anesthetic breakdown.
AB  - OBJECTIVE: Trifluoromethane and CO are produced simultaneously during the
      breakdown of isoflurane and desflurane by dry CO2 absorbents. Trifluoromethane
      interferes with anesthetic agent monitoring, and the interference can be used as
      a marker to indicate anesthetic breakdown with CO production. This study tests
      representative types of gas monitors to determine their ability to provide a
      clinically useful warning of CO production in circle breathing systems. METHODS:
      Isoflurane and desflurane were reacted with dry Baralyme at 45 degrees C.
      Standardized samples of breakdown products were created from mixtures of reacted
      and unreacted gases to simulate the partial degrees of reaction which might
      result during clinical episodes of anesthetic breakdown using 1% or 2% isoflurane
      and 6% or 12% desflurane. These mixtures were measured by the monitors tested,
      and the indication of the wrong agent or a mixture of agents due to the presence
      of trifluoromethane was recorded and related to the CO concentration in the gas
      mixtures. RESULTS: When presented with trifluoromethane from anesthetic
      breakdown, monochromatic infrared monitors displayed inappropriately large
      amounts of isoflurane or desflurane. Agent identifying infrared and Raman
      scattering monitors varied in their sensitivity to trifluoromethane. Mass
      spectrometers measuring enflurane at mass to charge = 69 were most sensitive to
      trifluoromethane. CONCLUSION: Monochromatic infrared monitors were unable to
      indicate anesthetic breakdown via interference by trifluoromethane, but did
      indicate falsely elevated anesthetic concentrations. Agent identifying infrared
      and Raman monitors provided warning of desflurane breakdown via the interference
      of trifluoromethane by displaying the wrong agent or mixed agents, but may not be
      sensitive enough to warn of isoflurane breakdown Some mass spectrometers provided
      the most sensitive warnings to anesthetic breakdown via trifluoromethane, but
      additional data processing by some patients monitor units reduced their overall
      effectiveness.

PMID- 9234085
TI  - An algorithm for real-time, continuous evaluation of left ventricular mechanics
      by single-beat estimation of arterial and ventricular elastance.
AB  - We describe a computer algorithm that allows continuous, real-time evaluation of
      ventricular elastance (Ees), arterial elastance (Ea), and their coupling ratio in
      a clinical setting. In the conventional pressure-volume analysis of left
      ventricular (LV) contractility, invasive methods of volume determination and a
      significant, rapid preload reduction are required to generate Ees. With the help
      of automated border detection by transesophageal echocardiography, and a
      technique of estimating peak LV isovolumic pressure, Ea and Ees were determined
      from a single cardiac beat without the need for preload reduction. A comparison
      of results obtained by a conventional approach and the new algorithm technique,
      showed good correlation for Ea (r = 0.86, p < 0.001) and Ees (r = 0.74, p =
      0.001). Bias analysis showed a bias (d) of 1.47 mmHg/cm2 for Ea with a standard
      deviation (SD) of 7.03 mmHg/cm2, and upper (d+2SD) and lower(d-2SD) limits of
      agreement of 15.24 mmHg/cm2 and -12.31 mmHg/cm2, respectively. Bias analysis
      showed a bias of -1.42 mmHg/cm2 for Ees with a SD of 4.88 mmHg/cm2, and limits of
      agreement of 8.15 mmHg/cm2 and -10.98 mmHg/cm2. The algorithm's stability to
      artifacts was also analyzed by comparing magnitudes of residuals of Ea and Ees
      from source signals with and without noise. With Ea differing by an average of
      1.036 mmHg/cm2 and Ees differing by an average of 0.836 mmHg/cm2, the algorithm
      was found to be stable to artifacts in the source signals.

PMID- 9234086
TI  - Performance of anesthesia machines' devices that are not part of the Food and
      Drug Administration's daily checkout.
AB  - OBJECTIVE: The Food and Drug Administration's (FDA) checkout recommendations are
      to be applied, at least daily, on anesthesia machines. Devices included in the
      checkout are crucial to the safe operation of the machine. Remaining devices do
      not need to be checked as often. However, they should be checked at some
      appropriate interval. We calculated the reliability of the non-FDA checkout
      devices, to predict failure rates of these devices. METHODS: The study included
      36 North American Drager Narkomed anesthesia machines that were in service a
      total of 109,410 days at a university hospital. Reliability (i.e., statistical)
      analyses were done using in-house data recorded by biomedical technicians during
      3359 monthly machine inspections. If any one device was operating outside of the
      limits of the manufacturer's specifications, the machine was labeled as having
      failed its inspection. RESULTS: Assumptions of the failure analysis were
      satisfied. The mean time between failures equaled 1351 days or 3.7 years (lower
      95% confidence bound 1123 days or 3.1 years). The mean daily probability of one
      or more devices failing to perform within the manufacturer's specification
      between inspections equaled 1.1, 2.2%, and 4.4% for inspections every 1, 2, or 4
      months, respectively. Probabilities that a machine would fail on demand between
      inspections were approximately equal to the mean daily probabilities of machine
      failure. The mean number of days per year that a machine would be operating with
      a device that is outside of the limits of its specifications equaled 4, 8, and
      12, days, respectively. The mean daily probabilities of failure and the
      probabilities of failure on demand were both directly proportional to the
      inspection interval. CONCLUSIONS: Our failure analysis provides a rational basis
      for choosing an appropriate inspection interval for anesthesia machines' devices
      that are not included in the FDA's checkout recommendations.

PMID- 9234087
TI  - Response time studies of a new, portable mass spectrometer.
AB  - OBJECTIVE: Mass spectrometers are frequently used by anesthesiologists
      perioperatively to monitor patients' respiratory function and levels of inhaled
      anesthetics. Due to size, complexity and expense, they are typically used in a
      time-sharing manner which degrades their performance. We assessed the accuracy of
      the Random Access Mass Spectrometer (RAMS), Marquette Electronics) which is small
      enough to be dedicated to a single patient. METHODS: We compared the 10-90% rise
      times for O2, CO2, N2O and isoflurane for the RAMS with different catheter
      configurations to those of a MedSpect mass spectrometer (Allegheny International
      Medical Technology) operating under ideal conditions. For CO2 the lag of the RAMS
      relative to the MedSpect was also measured. Next, perioperative conditions were
      stimulated by ventilating anesthetized dogs with a variety of inhalatory gases
      and ventilatory parameters, and the interchangeability of the two devices was
      assessed. RESULTS: When fitted with a catheter with minimal dead space the
      MedSpect had rise times of 0.11-0.12 sec while the RAMS had rise times of 0.07
      0.12 sec and a delay of 0.19 sec compared to the MedSpect. The rise times and
      delay of the RAMS increased when using a larger catheter and water trap. Although
      there were statistically significant differences in some values for inhaled and
      end-tidal gases under simulated perioperative conditions, particularly at the
      higher frequencies, these differences were small and for most purposes not
      clinically significant. CONCLUSIONS: Our results demonstrate that the RAMS
      configured for clinical conditions performs nearly as well as the MedSpect under
      ideal conditions. The small differences between the two, confined almost entirely
      to their end-tidal CO2 values, could be due to differences in instrument
      calibration, by the larger sampling catheter commonly used in clinical settings,
      or by a combination of both factors. Therefore the RAMS is sufficiently accurate
      for clinical use and would alleviate problems associated with time-shared mass
      spectrometers.

PMID- 9234088
TI  - Evaluation of the AVOXimeter: precision, long-term stability, linearity, and use
      without heparin.
AB  - OBJECTIVES: Because the AVOXimeter uses disposable cuvettes and makes its
      measurements directly in whole blood without first hemolyzing the sample, it does
      not need the care and maintenance that conventional co-oximeters require, it
      operates faster than conventional co-oximeters, and it is less expensive.
      Therefore, the objectives of the study were (1) to evaluate the precision and
      linearity of the AVOXimeter's measurements of total hemoglobin concentration and
      oxyhemoglobin saturation; (2) to assess its long-term stability and thus the
      required interval for recalibration; (3) to determine whether measurements can be
      made without anticoagulants; and (4) to assess the feasibility of storing blood
      samples in the disposable cuvettes. METHODS: Measurements made by the test
      instrument were compared with those of conventional co-oximeters or with
      standardized hemoglobin solutions. Blood samples were also collected with and
      without heparin to determine whether anticoagulation is necessary. RESULTS: Our
      tests confirmed the specified precision of 0.3 g/dl for total hemoglobin and 0.5%
      for oxyhemoglobin. The results also showed that these measurements were linear
      when compared with a conventional co-oximeter, and they were consistent with the
      specified accuracy of 0.45 g/dl for total hemoglobin and 1% for oxyhemoglobin.
      Weekly checks with control solutions showed that the instrument holds its
      calibration for a year or more. Although treating syringes with heparin caused
      dilution errors, heparin did not affect the measurements when dilution was
      avoided. When blood samples were placed in disposable cuvettes and read
      repeatedly at 1-min intervals for 20 min, the readings drifted appreciably away
      from the original value. This drift occurred so slowly that readings taken at the
      first and second minute after the cuvette was filled were within 1 or 2% of the
      original reading. CONCLUSIONS: In our experience the test instrument was simple
      and easy to operate. It met the specification for precision and accuracy, its
      measurements were highly linear, and it maintained a stable calibration for one
      year. If the cuvettes are filled as soon as blood is drawn, anticoagulation is
      unnecessary. However, the cuvettes should be read with 1 min of filling the
      cuvette.

PMID- 9234089
TI  - Management of unilateral temporomandibular ankylosis associated with facial
      asymmetry.
AB  - Longstanding unilateral temporomandibular joint ankylosis, which starts during
      the active growth period in early childhood, results in facial asymmetry. Three
      problems are encountered: the ankylosed joint; the asymmetric face and,
      occasionally, upper airway obstruction. Simultaneous surgery was performed on 27
      patients to release the joint ankylosis and to correct the facial deformity.
      Bimaxillary surgery was done for adult patients with occlusal canting, and
      mandibular surgery alone for adult patients without occlusal canting and for
      young children. Very satisfactory results were obtained during a follow-up period
      ranging from 2 to 6 years, regarding the restoration of joint function,
      improvement in aesthetic appearance and relief of respiratory obstruction.

PMID- 9234090
TI  - Submerged intraoral device for mandibular lengthening.
AB  - The authors report a new technique for mandibular distraction. Lengthening of the
      mandible by gradual intraoral distraction was obtained in nine young patients. An
      intraoral device was used in order to avoid external scars. Seven patients had
      hemifacial microsomia, one patient had a ramus hypoplasia after TMJ ankylosis and
      one patient had the Treacher-Collins syndrome. The amount of mandibular
      lengthening ranged from 12 to 28 mm depending on the duration of expansion.
      Retention after expansion, to allow ossification to take place, lasted for 3
      weeks on average. The follow-up period ranged from a minimum of 5 months to a
      maximum of 44 months.

PMID- 9234091
TI  - Long-term results of hydroxyapatite-fibrin glue implantation in plastic and
      reconstructive craniofacial surgery.
AB  - The bone tissue formed in orthotopic or heterotopic implants of granular, porous
      hydroxyapatite and fibrin glue was examined several (2 1/2-8) years after
      implantation. The results showed distinct ossification in all cases and the
      functional situation and external appearance were also satisfactory. The
      reconstituted spongy and compact bone underwent a remodelling process similar to
      that of normal bone. Most of the hydroxyapatite granules were embedded in the
      bone tissue; a few were very close to the fibrillar connective tissue of the
      intertrabecular spaces and were either covered by osteoid-like collagenous
      borders or were in contact with osteoclast-like giant cells. Even if the results
      refer only to a few patients, and were obtained from a cross-sectional study,
      they allow the conclusion to be reached that the implantation of porous
      hydroxyapatite and fibrin glue leads to the formation of long-lasting bone whose
      hardness is equal to, or greater than, that of normal bone.

PMID- 9234092
TI  - Remote stereotactic visualization for image-guided surgery: technical innovation.
AB  - Additional data from imaging sources using computer navigation assistance enables
      virtual visualization of anatomical structures in three dimensions for
      stereotactic navigation during an operation. Recent developments in communication
      technology enable the broadcasting not only of video data, but also of
      stereotactic navigation data via the network. By telepresence/teleconsulting, the
      composite images and overlapping graphics (instrument, target structure,
      landmark, contour) can be seen in connected clinics, with the possibility of
      interactive graphic assistance. In cranio-maxillofacial surgery, the first
      surgical teleconsultation in real time via telecommunication of stereotactic data
      was performed in August 1996. A patient suffering from a post-traumatic deformity
      following multiple comminuted midface fractures was re-osteotomized with the aid
      of image-guided surgery using teleconsultation: the intraoperative position
      achieved could be discussed with different surgeons with regard to symmetry,
      hard/soft tissue relationships and occlusal details, with the possibility of on
      screen planning interaction and real time evaluation of the results, over a
      distance of 500 km.

PMID- 9234094
TI  - Detection of latero-cervical metastases from oral cancer.
AB  - In squamous cell carcinoma of the oral cavity, the presence of nodal metastases
      greatly influences prognosis. The evaluation of regional lymph nodal involvement
      is crucial in the correct management of these neoplasms. The records of 45
      patients with oral cancer were reviewed retrospectively to evaluate the accuracy
      and prognostic value of the techniques used to detect lymph node metastasis in
      the neck (clinical examination, echo-colour-Doppler, computed tomography and
      magnetic resonance imaging). Echo-colour-Doppler was the most accurate procedure
      with a predictive positive value of 95.6% and the lowest false-negative rate.
      Therefore, a diagnostic preoperative study must include echo-colour-Doppler
      preferably associated with computed tomography to achieve the greatest diagnostic
      accuracy.

PMID- 9234093
TI  - Morphometric and morphological changes in the temporomandibular joint after
      orthognathic surgery: a magnetic resonance imaging and computed tomography
      prospective study.
AB  - The possible morphological and morphometric changes in the different components
      of the temporomandibular joint (TMJ) after orthognathic surgery were analysed
      using computed tomography (CT) transverse scans and sagittal and coronal magnetic
      resonance imaging (MRI) images. Twenty-four patients with class III dentofacial
      deformity were studied. Nine had isolated maxillary osteotomies and 15 had
      combined maxillary and mandibular subcondylar osteotomies (MSO). Ten patients
      were studied as a control group. The patients were studied clinically,
      radiographically and with CT and MRI in four different phases in order to locate
      the position of the mandibular condyle in relation to the glenoid fossa. No
      statistically significant differences were found in the group of patients who had
      had isolated maxillary osteotomies throughout the four phases of the study.
      Patients treated by bimaxillary surgery showed different condylar movements after
      surgery. Intra-articular effusion was evident during the early postoperative
      period in patients treated by bimaxillary surgery. Although different changes in
      the position of the bony components of the TMJ occurred after MSO, these seemed
      to be transient, with no major alterations in the final outcome in the patients.

PMID- 9234095
TI  - Quintuple cancers: report of a case with triple cancers in the head and neck.
AB  - The incidence of multiple primary cancers is increasing. We report a case of
      quintuple cancers, two located in the genitourinary tract and three arising on
      the upper aerodigestive tract, two synchronous squamous cell carcinomas of the
      oral mucosa and another on the larynx. We also present a brief review of the
      literature.

PMID- 9234096
TI  - Maxillomandibular deformity in association with Poland anomaly.
AB  - A case of jaw deformity in association with right-sided Poland anomaly in an 18
      year-old male patient is presented. As there have been no cases previously
      reported of pectoralis major muscle hypoplasia combined with dentofacial
      deformity, it is hoped that other reports would emerge to describe a new
      syndrome.

PMID- 9234097
TI  - One- or two-plate fixation of mandibular angle fractures?
AB  - Standard treatment of mandibular angle fractures with miniplates, according to
      the recommendations of Champy et al. (1976), consists of fixation with one plate
      at the superior border of the mandible ventral to the external oblique line. In
      certain constellations, a second miniplate at the lower mandibular margin may
      provide additional stability. In contrast, extremely high complication rates
      following two-plate fixation of mandibular angle fractures were reported by Ellis
      and Walker (1994). In a prospective randomized study, 31 consecutive patients
      were treated with 2.0 mm (mini) plates (Synthes Co., Switzerland). One group was
      treated with one plate, the other one with two plates. In none of the patients
      was intermaxillary immobilization used. Follow-up was performed 6 months
      postoperatively, consisting of clinical and radiographic examination. No
      significant differences (P = 0.74 for infection, and P = 1.0 for occlusal and
      postoperative sensory disturbance) in postoperative short- or long-term
      complications were found between the two groups. The results are compared with
      our experimental investigations presented at the annual congress of the Germany
      Society of Oral and Maxillofacial Surgery, 1995. Two-plate fixation may not offer
      advantages over single-plate fixation in general. However, individual fracture
      constellations may benefit from variation in plate(s) localization. Factors
      contributing to complications in mandibular angle fractures are discussed.

PMID- 9234098
TI  - Hyperplasia of the mandibular coronoid process: long-term follow-up after
      coronoidotomy.
AB  - The aim of this study was to evaluate long-term results of treatment by intraoral
      coronoidotomy and prolonged physiotherapy in five patients with mandibular
      coronoid process hyperplasia. Five consecutive cases of coronoid process
      hyperplasia were studied (two unilateral and three bilateral) at the Department
      of Maxillo-facial Surgery of the University of Turin during the period 1985-1990.
      All patients were treated by intraoral coronoidotomy and given physiotherapy from
      the third postoperative day. This continued for an entire year. A clinical and
      radiological follow-up (average 39.4 months), in three cases over a 5-year
      period, was completed. Three months after the operation, all patients had
      achieved satisfactory improvement in mandibular interincisal opening. The mean
      value for mouth opening at the end of follow-up was 42 mm. Radiographic follow-up
      showed the presence of a coronoid process almost the size of the original,
      apparently united with the mandibular ascending ramus, with moderate dislocation
      and inclination posterior to the body of the zygomatic bone. The results of this
      study indicate that treatment of coronoid process hyperplasia by intraoral
      coronoidotomy, when combined with prolonged postoperative physiotherapy, gives
      satisfactory and stable long-term results in the correction of coronoid-malar
      interference.

PMID- 9234099
TI  - Prefabrication of combined scapula flaps for microsurgical reconstruction in oro
      maxillofacial defects: a new method.

PMID- 9234100
TI  - Thrombolytic therapy in acute stroke.
AB  - PURPOSE: To report the safety and efficacy of local, direct, intra-arterial and
      intravenous fibrinolysis treatment in selected cases of clinically symptomatic
      patients with acute occlusion of the intracranial cerebral arteries and dural
      sinuses. METHODS: Patients with acute progressive neurological deterioration, in
      spite of systemic anticoagulation and/or antiplatelet medications, presenting
      with occlusion of a major intracranial cerebral artery or dural sinus were
      tested. From a transfemoral approach through a guiding catheter, a 2.5F
      microcatheter was guided directly into the intracranial cerebral circulation and
      embedded within the clot. Infusion of urokinase was then performed directly into
      the thrombus until lysis was attained. RESULTS: In 36 total patients, 27 cases
      were treated for an acute arterial occlusion in 45 vascular territories.
      Clinically, there was neurological improvement in 18 (66.7%) cases. Complications
      directly related to therapy included symptomatic intracranial hemorrhage in three
      cases (11.1%), which included 1 case (3.7%) of vessel perforation. In 8 (29.6%)
      patients, there was no evidence of clinical improvement, and in long-term follow
      up there were 9 (33.3%) patient deaths. Nine patients were treated for an
      intracerebral dural sinus thrombosis in ten vascular territories by local
      urokinase infusion. In 7 (77.8%) cases, there was angiographic evidence of clot
      lysis and clinical improvement of the patient's neurological condition. Minor
      complications including infection and noncerebral sites of bleeding occurred in 3
      (33.3%) patients, requiring adjustment in urokinase infusion therapy. CONCLUSION:
      Local, direct intra-arterial or intravenous infusion of thrombolytic drugs for
      treatment of stroke patients may improve overall patient morbidity and mortality
      related to acute thromboembolic disease in the central nervous system. Further
      clinical studies are warranted to evaluate this form of therapy.

PMID- 9234101
TI  - A new nonstented balloon-expandable graft for straight or bifurcated endoluminal
      bypass.
AB  - PURPOSE: The aim of this study was to determine the feasibility of endoluminal
      grafting of aneurysms using a new design of nonstented endograft. METHODS:
      Initial studies were undertaken in bench models and by implantation of endografts
      into animal vessels. Between May 1992 and June 1994, endoluminal repair of
      aneurysms was undertaken in 47 patients (44 male, 3 female). A new balloon
      expandable endoluminal graft was developed and has now been studied in 25 of
      these 47 cases. This graft does not require adjunctive use of a vascular stent
      because of its unique construction, which incorporates metallic implants (graft
      attachment device or "GAD") into the graft material. The design is applicable to
      endovascular grafting of occlusive arterial disease, as well as aneurysms. All
      patients were investigated by duplex scan, calibrated angiogram, and angio-CT
      scan and then allocated into groups that we defined according to the following
      criteria: group I, considered suitable for transfemoral implantation of a
      straight tube graft (n = 12); group II, unsuitable for transfemoral tube graft
      because of short neck of aneurysm, absent distal neck, or diseased iliac arteries
      (n = 10); and group III, peripheral aneurysms (n = 3). All patients were followed
      by clinical examination, duplex scan, and CT scan, with selective use of
      angiography. RESULTS: Intraluminal deployment of the graft was achieved in all 25
      patients; however, 3 patients from group II subsequently required conversion to
      open procedures because of the following complications: (1) partial graft
      thrombosis resulting from inadvertent omission of systemic anticoagulation during
      deployment (n = 1); and (2) unsuccessful deployment of the contralateral limb of
      a bifurcated graft in the iliac artery (n = 2). Successful endoluminal repair was
      achieved in 100% of patients in groups I and III, compared to 70% in group II.
      CONCLUSIONS: These preliminary results (in a series of high-risk patients) have
      demonstrated that endoluminal abdominal aortic aneurysms repair with this graft
      can be achieved reliably and with low morbidity in patients who fulfill the
      selection criteria (group I) and in peripheral aneurysms (group III) but the
      results were less satisfactory in aneurysms that do not have a good proximal or
      distal neck or in patients with diseased iliac arteries (group II). Further
      modification of the bifurcated version in this graft design, together with
      improvements in access techniques and graft materials, is required for successful
      endoluminal grafting in a wider range of patients.

PMID- 9234102
TI  - Ultrasonic endarterectomy: experimental and initial clinical results in carotid
      stenosis.
AB  - PURPOSE: The effects of ultrasonic endarterectomy, evaluated experimentally and
      clinically, were compared with the results obtained with controversial
      endarterectomy. METHODS:  EXPERIMENTAL: An ultrasonic vascular dissector with a
      frequency of 29 kHz was used for ultrasonic endarterectomy. Gross and histologic
      observation was made on 22 fresh human cadaver atherosclerotic vessels, of which
      16 were treated with ultrasound endarterectomy and 6 conventionally. Clinical:
      Twenty-eight patients requiring carotid endarterectomy were chosen at random.
      Seven patients underwent ultrasonic endarterectomy after traditional access
      surgery, while 21 patients were treated with conventional endarterectomy. In the
      clinical study, an intraoperative gross observation of the endarterectomized
      surfaces was made, followed by duplex scanning after 18 and 24 months. RESULTS:
      Histologic observation of the cadaveric revealed particularly smooth surfaces in
      87.5%; there was no debris, flaps, or vessel damage in any of the ultrasonically
      treated samples. In contrast, the traditional technique produced regular surfaces
      without residual debris in only 50% of the experimental cases. Favorable results
      were also seen in the clinical carotid experience, in which there was no need to
      surgically correct the ultrasonically endarterectomized surface in any case. In
      fact, achieving a satisfactory outcome was greatly facilitated by the use of
      ultrasound. In the conventionally treated patients, however, only 19% (4)
      demonstrated a smooth luminal surface on gross observation even after surgical
      correction. No postoperative complications were encountered in either group, and
      no restenosis has occurred in ultrasonic endarterectomy-treated patients after 2
      years. CONCLUSIONS: Favorable experimental results using ultrasonic
      endarterectomy prompted the successful clinical application of this new technique
      in carotid stenosis treatment. Whether or not ultrasonic endarterectomy can
      reduce postoperative morbidity and restenosis is still under study.

PMID- 9234103
TI  - Initial experience with the Cragg Endopro System 1 for intraluminal treatment of
      peripheral vascular disease.
AB  - PURPOSE: To evaluate the safety and efficacy of a new covered stent, the Cragg
      Endopro System 1, for intraluminal treatment of peripheral vascular disease in
      the iliac and femoropopliteal arteries. METHODS: Forty symptomatic patients with
      predominantly lengthy stenotic (24) or occlusive (13) lesions or aneurysms (3) in
      the iliac (19), femoral (19), or popliteal (2) arteries were treated
      percutaneously with balloon angioplasty followed by implantation of the self
      expanding nitinol Cragg stent covered by a woven polyester fabric coated with low
      molecular-weight heparin. The mean length of femoropopliteal lesions was 13.0 +/-
      1.8 cm, as compared to 6.7 +/- 0.8 cm (p < 0.01) for iliac lesions. Mean percent
      stenosis was 89% +/- 2% with no significant difference between the arterial
      segments. RESULTS: With a total of 52 covered stents implanted, technical success
      was achieved in 98% (39/40 patients). One tortuous femoral artery aneurysm was
      not satisfactorily excluded to prevent leakage. Clinical success was seen in all
      patients with demonstrable improvements in the claudication stage and the ankle
      brachial index from a mean 0.54 to 0.92. Three local complications (one hematoma,
      two false aneurysms) required surgical repair. One distal embolism, one acute
      thrombosis, and three subacute thromboses were encountered and successfully
      treated by thrombolysis and/or surgery. One patient with two iliac stents
      developed contralateral common iliac artery occlusion from a stent partially
      obstructing the aorta; placement of a covered stent in the blocked artery re
      established normal flow. Over an 8-month follow-up with arteriographic re
      examination, all iliac stents remained patent. At the femoropopliteal level, two
      stents were occluded at 4 months; one was successfully dilated, but the other
      required surgical bypass grafting. A third patient developed a stenotic lesion
      proximal to the stent; dilation restored adequate inflow to the stent.
      CONCLUSIONS: The Cragg Endopro System 1 appears to be effective as an "internal
      bypass" for iliac and femoropopliteal occlusive disease. More complications and
      restenosis were seen in femoropopliteal implantations; however, a change in
      postoperative medication may improve these results. Long-term results will
      determine if the Cragg Endopro System 1 can achieve a patency equal to
      conventional bypass grafting.

PMID- 9234104
TI  - Endoluminal grafting of abdominal aortic aneurysms: causes of failure and their
      prevention.
AB  - PURPOSE: The aim of this study was to analyze the causes of failure of
      endoluminal grafting for abdominal aortic aneurysms (AAA) and to put forward
      proposals for preventing these failures. METHODS: Since May 1992, endoluminal
      repair of aneurysms was undertaken in 47 patients. Forty-three of these patients
      had AAAs and are the basis of this study. All procedures were nonurgent and were
      performed in the operating room with the patient draped for an open repair in the
      event of failed endoluminal repair. Radiographic guidance was used to pass the
      endografts into the aorta via a delivery sheath introduced through the femoral or
      iliac arteries. The configuration of the endografts was tubular (n = 28), tapered
      aortoiliac/aortofemoral (n = 11), and bifurcated (n = 4). RESULTS: Successful
      endoluminal repair was achieved in 34 of 43 (79%) patients. The remaining nine
      were terminated in favor of an open repair. The causes of failure were problems
      with access (2), balloon malfunction (1), stent dislodgment (3), graft thrombosis
      (1), and inability to deploy the contralateral limb of a bifurcated graft (2).
      All failed endoluminal repairs proceeded to successful open repair. There was no
      perioperative mortality in patients undergoing endoluminal repair or in those
      whose endoluminal repair was converted to open operation. CONCLUSIONS: The
      failures of endoluminal grafting have been analyzed. Methods of avoiding access
      problems, balloon malfunction, and stent dislodgment have been defined and
      recommendations made.

PMID- 9234106
TI  - Infrainguinal atherectomy using the transluminal endarterectomy catheter: patency
      rates and clinical success for 144 procedures.
AB  - PURPOSE: To determine if atherectomy using the transluminal endarterectomy
      catheter (TEC) is an effective endoluminal therapy for infrainguinal occlusive
      disease. METHODS: Three surgeons used the TEC for 144 infrainguinal atherectomy
      procedures in 133 patients. The indications were severe claudication in 83,
      critical ischemia in 56, and graft stenosis in 5 limbs. The pathology was
      stenosis in 36 and occlusion in 105 limbs. Balloon dilation was also performed in
      109 and stenting in 17 limbs. RESULTS: There was initial technical and anatomic
      success in 124 (86%) procedures. There were 67 technically successful procedures
      at mean follow-up of 19 months, although 3 of these limbs with gangrene and
      extensive distal disease required major amputation. There were 26 failures due to
      stenosis leading to further intervention and 51 due to occlusion. Twenty of these
      cases were managed conservatively, 21 were treated with repeat endovascular
      intervention, 31 with bypass grafting, and 5 with amputation. Repeat intervention
      in 52 limbs resulted in 36 with patent arteries, 10 that are occluded, and 6 that
      required amputation. Thirteen of the 14 amputations were for limbs with critical
      ischemia, but 1 was in a patient with claudication. Life-table analysis showed
      that the primary patency rate was 51%, the assisted primary patency rate was 61%,
      and the secondary patency rate was 75% at 15 months. The clinical success rate
      was 49%, and the salvage rate for limbs with critical ischemia was 78% at 12
      months. Univariate log-rank testing showing no significant differences according
      to the clinical presentation of pathology, but results were worse for lesions > 5
      cm long due to more frequent immediate failures. However, multivariate Cox
      regression analysis showed that results were significantly worse for critical
      ischemia than for claudication, stenosis compared to occlusions, for limbs with
      poor runoff, for operations performed by percutaneous rather than an open
      approach, and for those performed more recently. CONCLUSIONS: TEC atherectomy may
      have a place in selected patients, but the optimal circumstances for its use and
      long-term efficacy require further study.

PMID- 9234105
TI  - Percutaneous angioplasty, endothelial markers, and fibrin turnover.
AB  - PURPOSE: A number of thrombotic mediators have been related to peripheral
      arterial disease in both epidemiological and pathological studies. METHODS: We
      measured preoperative levels of fibrinogen, cross-linked fibrin degradation
      products (FDP), and the endothelial markers, von Willebrand factor (vWF), tissue
      plasminogen activator (tPA), and plasminogen activator inhibitor (PAI), in the
      venous blood of 43 claudicants undergoing percutaneous transluminal angioplasty
      (PTA). Samples were repeated 4 months later, and changes in the levels of
      thrombotic mediators were compared with ten controls undergoing angiography
      alone. Additional perilesional arterial samples were obtained from 11 of the
      patients. RESULTS: Arterial sampling indicated that successful PTA led to an
      immediate fall in tPA levels and a rise in arterial vWF (p < 0.05), together with
      a trend toward a significant rise in cross-linked FDP levels. Only the increase
      in FDP following successful PTA (36 cases) (p < 0.05) was observed in 4-month
      postangioplasty venous samples, whereas all variables remained unchanged in cases
      of restenosis (4 patients) and in controls (all comparisons made by Wilcoxon
      matched pairs test). CONCLUSIONS: These findings suggest that successful PTA in
      patients with intermittent claudication results in acute endothelial disturbance
      and increased fibrin turnover at the site of angioplasty and in sustained
      increases in fibrin turnover (as reflected by FDP levels). The observation that
      this increase in fibrin turnover is absent in cases of restenosis within 4 months
      of PTA merits further study to determine whether increases in fibrin turnover are
      necessary to maintain patency following PTA.

PMID- 9234107
TI  - Intravascular ultrasound guidance for peripheral vascular interventions.
AB  - Intravascular ultrasound (IVUS) imaging during peripheral endovascular
      interventions adds important information regarding the distribution of disease by
      providing controlled measurements of the cross-sectional area of the vessel lumen
      and wall prior to and following procedures. IVUS is useful in determining the
      mechanism and efficacy of balloon angioplasty, in guiding atherectomy devices,
      and in assuring appropriate placement of intravascular stents. The incorporation
      of an IVUS element into catheter-based interventional devices may improve the
      immediate and long-term results of endovascular interventions by decreasing
      complications from dissection and perforation of the arterial wall. Combined IVUS
      stent prototype catheters are being developed to enable imaging and deployment
      simultaneously. Similar devices are being explored to enhance expedient, precise
      delivery of endoluminal grafts. Future studies of endovascular techniques should
      include IVUS, when possible, to accurately quantitative the initial efficacy of
      devices and to determine the nature and distribution of recurrent lesions.

PMID- 9234108
TI  - PTA and thrombolysis in leg salvage.
AB  - PURPOSE: The goals of any treatment for ischemic vascular disease are to relieve
      pain, allow wound healing, and regain/maintain ambulatory abilities. To determine
      if endovascular therapy could accomplish these goals in patients with limbs at
      risk, we undertook a retrospective analysis of the results of percutaneous
      transluminal angioplasty (PTA) and thrombolysis in leg salvage. METHODS: Over an
      8-year period ending in 1993, 327 patients (209 males, 118 females) with limb
      threatening ischemia (defined as one or more of the following: ischemic rest
      pain, ischemic ulceration, or gangrene) in 361 limbs were seen. These patients
      had an ankle-brachial index < or = 0.40 in nondiabetic patients and/or toe
      brachial index < or = 0.30 in diabetic patients. The patients were treated with
      thrombolysis and/or PTA according to standard techniques; intravascular stenting
      was used occasionally as required to treat PTA deficiencies or inadequate
      recanalization. RESULTS: Among the 327 patients, 805 arteries and 25 thrombosed
      arterial grafts were treated. The arteries treated were: 6 aorta (0.75%), 75
      iliac (9.3%), 34 common femoral (4.2%), 3 deep femoral (0.4%), 235 superficial
      femoral (29.2%), 219 popliteal (27.2%), 193 infrapopliteal (24.0%), and 40 pedal
      (5.0%). The patients were treated primarily with PTA (n = 307); urokinase
      thrombolysis (n = 99) and stents (n = 12) were used less frequently. Procedural
      success was 92.5%. Patients were followed from 6 months to 8 years (mean 3
      years). Eighty-three patients were retreated during this time. Of the 249
      patients available for this follow-up, total salvage was achieved in 181 (72.7%).
      Nineteen patients (7.6%) underwent minor amputations (e.g., toes); 4 patients
      (1.6%) had transmetatarsal amputation. Fifteen patients (3.6%) had above-knee
      amputation despite successful recanalization. In all, 32 patients (8.8%) had the
      amputation level extended from above to below knee, bringing the total leg
      salvage rate to 82% (defined as patients able to ambulate without any
      prosthesis). Using life-table analysis, the 5 year survival rate was 71%.
      CONCLUSION: This study shows that endovascular therapy for leg salvage is as
      effective as reconstructive vascular surgery in achieving wound healing and
      maintaining ambulation and has a more favorable 5-year survival rate.

PMID- 9234109
TI  - Wound Healing: An endpoint for complex peripheral angioplasty.
AB  - PURPOSE: The standard endpoint for lower limb revascularization is long-term
      patency; however, in high-risk patients with end-stage ischemia, healing of
      chronic ulcerations has been proposed as an acceptable endpoint. To evaluate if
      today's minimally invasive interventions, in combination with comprehensive wound
      healing procedures, can resolve nonhealing wounds, we performed a retrospective
      review of chronic ulceration patients treated at the San Francisco Wound Care
      Center. METHODS: Eight-five patients with 96 limbs at risk due to nonhealing
      ulcers were treated with a variety of endovascular procedures: 7 patients (group
      I) received Palmaz stents for unilateral iliac occlusions; 42 limbs (group II) in
      39 patients were treated with balloon angioplasty for superficial femoral and
      popliteal lesions; and 47 extremities in 39 patients (group III) underwent
      rotational atherectomy for tibioperoneal lesions. Comprehensive wound management
      techniques, including the application of growth factors, were used. RESULTS: All
      group I wounds healed, although 6 of 7 patients required additional procedures to
      address outflow lesions. In groups II and III, primary patencies were similar
      (64% and 70%, respectively), and nine treated sites reoccluded in each group.
      Restenotic lesions were retreated in both groups (three in group II and four in
      group III) secondary patencies were 71% and 78%, respectively. There were more
      amputations in group III patients (five) compared to group II (one). In both
      groups after 5 months, 90% of wounds had healed in group II and 72% in group III.
      CONCLUSION: The use of endovascular procedures appears to play an important role
      in the healing of chronic lower extremity ulcerations in high-risk patients with
      end-stage ischemia.

PMID- 9234110
TI  - Endovascular surgery in daily practice: a re-appraisal.
AB  - For more than 10 years, endoluminal therapy has been marked by an explosion in
      the number and variety of devices designed to enhance or supplant its first and
      still most commonly used technique, balloon angioplasty. Among all these
      innovative catheter-based technologies, only stents have emerged as a truly
      effective device capable of achieving results comparable or superior to balloon
      angioplasty. In combination with thrombolysis and balloon dilation, they form the
      triadic foundation of endovascular surgery today. The prudent and judicious use
      of these tools, and a few other "niche" devices, such as atherectomy, in
      conjunction with classical vascular surgical techniques is the special and unique
      purview of the vascular surgeon. His development of a therapeutic plan, whose
      components include patient selection, lesion assessment, device decisions,
      procedure monitoring completion evaluation, and follow-up, is incumbent upon an
      appreciation of the capabilities of each available intraluminal device in the
      various arterial segments and lesion pathologies. The strategies that facilitate
      optimum matching of endoluminal tools and techniques to each patient situation
      form the basis of this report. They offer today's vascular surgeon a guide to the
      use of intraluminal therapies in daily practice. On the horizon is the new and
      exciting technique of endoluminal grafting, which, if it proves efficacious, will
      bring about profound changes in our specialty.

PMID- 9234111
TI  - Endovascular surgery and its effect on the relationship between vascular surgery
      and radiology.

PMID- 9234112
TI  - Fit to be tied: can vascular surgeons succeed playing catch-up?

PMID- 9234113
TI  - The role of routine angioscopy in vascular access surgery.
AB  - PURPOSE: The purpose of this retrospective study is to describe our techniques,
      review our experience, and determine the feasibility, safety, and role of the
      routine use of angioscopy during primary and revision vascular access surgery.
      METHODS: Between February 1991 and October 1993, intraoperative angioscopy was
      routinely performed in 84 consecutive operations (51 patients) for vascular
      access surgery. We reviewed the videotaped recordings of the angioscopic studies
      together with the clinical data according to a predetermined protocol. RESULTS:
      There were 43 primary procedures (36 autogenous arteriovenous fistulas and 7
      bridge graft fistulas) and 41 revision procedures for failed vascular access (7
      autogenous arteriovenous fistulas and 34 graft bridge fistulas). In 20.9% of the
      primary vascular access procedures, abnormal endoluminal findings were noted.
      Based on these findings, only one additional intervention was performed. In
      revision vascular access surgery, abnormal endoluminal findings were noted in
      92.7%, resulting in additional surgical interventions in 65.9% of the procedures.
      In the revised synthetic bridge graft fistulas, stenosis of the midgraft (n = 9)
      as a result of needle insertion for dialysis was more common than at venous
      anastomosis (n = 4). Detection and correction of endoluminal abnormalities
      resulted in a 30-day patency of 66.6% as opposed to 33.3% when none was detected
      (p < or = 0.012, Fisher's exact test). CONCLUSIONS: Routine angioscopy is
      technically feasible and can be performed safely in anuric patients during
      vascular access surgery. It provides additional and useful intraoperative
      information that may significantly alter the surgical procedure. Routine
      angioscopy may also provide new insights into the pathophysiology of vascular
      access failure.

PMID- 9234114
TI  - A new light on vascular access surgery.

PMID- 9234115
TI  - Peripheral transluminal angioplasty under ultrasound guidance: initial clinical
      experience and prevalence of lower limb lesions amenable to ultrasound-guided
      angioplasty.
AB  - PURPOSE: Currently, endovascular techniques require monitoring by radiographic
      imaging for accurate catheter placement. The aim of this study was first to
      determine the feasibility of angioplasty under ultrasound guidance using a
      special catheter system. Based on this outcome, the second goal was to
      investigate the prevalence of lesions amenable to ultrasound-guided angioplasty.
      METHODS: A balloon catheter system (Echomark) has been developed, which allows
      accurate catheter guidance by ultrasound imaging. An ultrasound-sensitive
      piezoelectric sensor positioned in the middle of the balloon portion of the
      angioplasty catheter is interfaced to an external duplex scanner via the catheter
      system. The exact position of the balloon relative to the transducer is
      calculated and reproduced on the screen of the duplex scanner to guide balloon
      positioning. In the feasibility assessment of the procedure, 16 patients with
      disabling claudication and rest pain were selected for balloon angioplasty under
      ultrasound guidance based on arteriographic and hemodynamic lesion criteria of >
      50% stenosis with a peak systolic velocity ration > 2.5 in a lesion < 4 cm long
      that could be imaged by duplex ultrasonography. A fall in the peak systolic
      velocity ratio below 2.0 was selected for a procedural endpoint corresponding to
      < 30% residual stenosis on the completion angiogram. In the second part of the
      study, the prevalence of stenoses amenable to ultrasound-guided angioplasty was
      studied in 80 patients presenting with symptoms of peripheral arterial disease.
      RESULTS: In the feasibility study, 20 stenoses (5 common iliac, 6 external iliac,
      and 8 superficial femoral arteries and 1 graft) meeting the inclusion criteria
      were subjected to ultrasound-guided angioplasty with confirmation by completion
      angiography. The procedure was possible in 18 (90%) of the 20 stenoses. The two
      failures occurred in iliac arteries that could not be imaged by duplex scanning
      due to obesity, bowel gas, and/or vessel wall calcification. In one case, the
      peak systolic velocity ratio exceeded 2.5 despite a satisfactory control
      arteriogram; redilation was performed, and the ratio fell below 2.0. In the
      second part of the study, 21 (26.2%) of the 80 patients had 29 stenoses that were
      amenable to angioplasty according to angiographic criteria (> 50% stenosis and <
      4 cm length). All these stenoses were evaluated with duplex scanning to determine
      their suitability for angioplasty under ultrasound guidance. Twenty-three (79%)
      of the 29 lesions selected for angioplasty were well visualized by duplex, and
      angioplasty would have been possible based on our initial clinical experience.
      CONCLUSIONS: Angioplasty under ultrasound control is a feasible technique for
      peripheral lesions. Ultrasound allows monitoring of both anatomical and
      hemodynamic parameters during angioplasty and thus provides a procedural endpoint
      that correlates to the control angiogram. A large proportion (79%) of stenoses
      deemed suitable for angioplasty can be well visualized by ultrasound, but
      obesity, vessel wall calcification, and bowel gas may limit the ability to obtain
      a satisfactory ultrasound image. Ultrasound-guided angioplasty is a potentially
      useful procedure that warrants further investigation.

PMID- 9234116
TI  - The role of endovascular surgery in carotid restenosis.
AB  - PURPOSE: To report the immediate and long-term outcome of intraoperative balloon
      angioplasty for the treatment of recurrent disease in the internal carotid
      arteries (ICAs). METHODS: Three patients (2 males, 1 female; ages 53 to 70 years)
      presented with > 80% restenotic lesions (bilateral in one patient) at the distal
      aspect of a previous carotid endarterectomy. Two patients exhibited hemianopia,
      while the third was asymptomatic but had a contralateral ICA occlusion. All four
      lesions appeared smooth and fibrous on ultrasonography and were located high in
      the ICA. The location and morphology of the lesions made balloon angioplasty a
      more potentially successful treatment option. RESULTS: Through open access to the
      common carotid artery, the lesions were approached and dilated under fluoroscopic
      guidance with monitoring of evoked potentials. The lesions were successfully
      dilated as determined by control arteriography, and no complications were
      encountered. Over a follow-up period extending to 18 months in one patient and 24
      months in the other two, ultrasound imaging and arteriography have shown no
      restenosis at any treatment site. CONCLUSIONS: Although caution is prudent when
      dealing with lesions in the cervical arteries, balloon angioplasty may have a
      role in treating surgically inaccessible restenotic carotid lesions that
      demonstrate a low potential for embolic complications. More experience with this
      technique will be required before widespread application of balloon angioplasty
      in the cervical vessels can occur.

PMID- 9234117
TI  - Iliac and femoropopliteal lesions: evaluation of balloon angioplasty and
      classical surgery.
AB  - PURPOSE: The purpose of this study was to compare the characteristics of patients
      treated for atherosclerotic disease of the lower extremities with balloon
      angioplasty (BA) or classical surgery (CS) and to assess the outcome of both
      techniques. METHODS: The records of 1364 patients who were treated with BA or CS
      for chronic lower limb ischemia between 1986 and 1993 were analyzed. Demographic
      features of patients, immediate and long-term survival, patency, and amputation
      rates were compared in both groups according to the level of the
      revascularization (iliac or femoropopliteal). RESULTS: Patients undergoing BA
      were slightly younger (62.3 years versus 65.9 years for CS group; p = NS) and
      demonstrated symptoms consistent with less severe atherosclerotic disease (81%
      claudication in the BA group versus 48% in the CS patients; p < 0.001). At 30
      days post-treatment in the BA and CS groups, respectively, there were 0.7% and 4%
      deaths (p < 0.01); 13% and 6% primary failures (p = 0.013); 13% and 6% secondary
      failures (p = 0.01); 0.3% and 12% general complications (p = 0.001); and 3% and
      8%, nonvascular complications (p = 0.007). At the iliac level, in the angioplasty
      (n = 134 limbs) and surgery (n = 721 limbs) groups, respectively, the mean age
      was 57.6 and 63.7 years (p < 0.01), and claudication was present in 91% and 72%.
      Perioperative mortality was 0% and 1.9%. The 4-year survival rates were 95% and
      88%; patency was 70% and 79%; and the amputation rates were 0% and 5%. At the
      femoropopliteal level, in the angioplasty (n = 138 limbs) and surgery (n = 656
      limbs) groups, respectively, the mean age was 67.8 and 66.8 years (NS), and
      claudication was present in 69% and 28%. Perioperative mortality was 0.9% and
      5.5%. The 4-year survival rates were 95% and 78%; and patency was 44% and 65%. At
      2 years, the amputation rates were 6% and 12%. CONCLUSIONS: Patients treated by
      BA were younger, especially in the iliac group, and had less symptomatic lesions
      than patients treated with surgery. Surgery achieved a better long-term patency
      at the cost of a higher immediate complication rate and mortality. Whenever
      technically feasible, BA may be the better choice for initial therapy in
      appropriate patients suffering from chronic lower limb ischemia.

PMID- 9234118
TI  - Percutaneous peripheral atherectomy using the rotablator: a single-center
      experience.
AB  - PURPOSE: In order to assess the role of percutaneous peripheral rotational
      ablation using Rotablator, 150 symptomatic patients (94 males, 56 females; mean
      age 73 +/- 1 years, range 42 to 90) having 212 complex peripheral vascular
      lesions were treated. METHODS: Fifty percent of lesions were below the knee; 65%
      of patients had severe claudication, 11% moderate (24% were in stage III or IV
      Fontaine classification). The femoral lesions were significantly longer than
      those at other sites (5.7 +/- 0.4 versus 2.9 +/- 0.3 cm, p < 0.001). The mean
      length was 4.0 +/- 0.2 cm (range 1 to 20). All the lesions were considered
      complex; 93% of the lesions were clacified, and 63% were located at a
      bifurcation. Complementary balloon dilation (percutaneous transluminal
      angioplasty [PTA]) was significantly (p < 0.001) more frequent in femoropopliteal
      lesions (70 PTAs in 86 femoral arteries, 10 PTAs in 19 popliteal arteries) than
      in distal leg lesions (14 in 106 arteries). RESULTS: After Rotablator therapy
      alone, the percent stenosis decreased from 81.0% +/- 0.8% to 18.0% +/- 1.1%. The
      residual stenosis was greater at the femoral (44%) than at the distal level (19%)
      (p < 0.01). Adjunctive PTA (47 lesions) lowered residual stenosis to 10% at the
      femoral level and 3% at the distal level. Thirty-seven intraprocedural
      complications occurred (spasm, thrombosis, dissection, perforation, distal
      emboli, no reflow); seven procedures subsequently failed for an overall technical
      success of 97%. The mean follow-up period was 14.4 +/- 1.0 months (range 1 to
      51). Among 125 patients having a follow-up period > or = 4 months, 114 patients
      representing 163 lesions underwent angiography. One hundred twenty-three lesions
      (76%) were patent, and 40 lesions (24%) showed restenosis (> or = 50% luminal
      narrowing) of 82.0% +/- 21%. The restenosis rate was higher in femoral (36%) than
      in distal (21%) or popliteal arteries (7%). Restenosis was more frequent for all
      lesions > or = 7 cm (p < 0.001) and for both above- and below-knee locations: 55%
      versus 19% for < 7 cm at the femoropopliteal level (p < 0.03), and 80% versus 18%
      at the distal level (p < 0.01). CONCLUSIONS: In our experience, percutaneous
      peripheral rotational ablation has taken a pre-eminent position in the treatment
      of distal leg arteries, especially in complex lesions. Our results have led us to
      broaden its indications to complex vascular lesions < or = 6 cm. In particular,
      the use of this technique for treatment of runoff vessels should improve the long
      term patency of proximal PTA and bypass grafts. This device has become
      indispensable in our laboratory, where Rotablator therapy comprises 15% of all
      PTA procedures.

PMID- 9234119
TI  - Infrainguinal atherectomy using the Auth Rotablator: patency rates and clinical
      success for 36 procedures.
AB  - PURPOSE: To determine whether the Auth Rotablator device is suitable for
      endoluminal atherectomy for infrainguinal occlusive arterial disease. METHODS:
      Two surgeons used the Auth Rotablator to perform 36 infrainguinal atherectomy
      procedures in 34 patients for severe intermittent claudication in 21, critical
      ischemia in 12, or graft stenosis in 3 limbs. There were 24 stenoses and 12
      occlusions. Adjuvant balloon dilation was performed in 13 limbs and stenting in
      5. RESULTS: There was initial technical and anatomical success in 34 procedures
      (94%), and 24 technically successful procedures persisted at mean follow-up of
      16.5 months, although 1 limb required major amputation. Three failures were due
      to stenosis requiring further intervention, and 9 were due to occlusion. Failure
      led to no further intervention in 2, amputation in 1, further endovascular
      intervention in 5, and open surgical reconstruction in 4 limbs. After further
      treatment, 29 limbs are patent with no return of symptoms, 3 are occluded, and 4
      have required amputation, all for initial presentation with critical ischemia.
      Life-table analyses calculate primary and secondary patency rates of 61% and 67%
      and a clinical success rate of 56% at 12 months. CONCLUSIONS: Atherectomy using
      the Auth Rotablator provides acceptable results, but its role in comparison to
      other endovascular techniques is still to be defined.

PMID- 9234120
TI  - Rotablator: the long and short of it.

PMID- 9234121
TI  - Subclavian stent implantation to alleviate coronary steal through a patent
      internal mammary artery graft.
AB  - PURPOSE: Interventional techniques are rapidly supplanting conventional surgical
      therapies for the treatment of brachiocephalic occlusive disease. Although
      coronary-subclavian steal has been successfully alleviated with subclavian
      angioplasty, we report the first use of a Palmaz stent in the left subclavian
      artery (SCA) of a patient with a compromised left internal mammary artery (IMA)
      graft. METHODS AND RESULTS: A 65-year old male patient had undergone triple
      coronary artery bypass grafting in 1992, but 6 months later, severe narrowing
      occurred in two of the saphenous vein grafts, and arteriography identified a high
      grade stenosis in the SCA supplying the left IMA graft to the left anterior
      descending coronary artery. Following balloon dilation of one saphenous vein
      graft stenosis, the left SCA was stented primarily with a P3008 Palmaz stent.
      Normal hemodynamics were restored, and the patient has been free of coronary
      steal symptoms for over 1 year. CONCLUSION: This case illustrates yet another
      aspect to the usefulness of intravascular stents in restoring and maintaining
      inflow to bypass grafts.

PMID- 9234122
TI  - Endoluminal grafting for percutaneous aneurysm exclusion in an aortocoronary
      saphenous vein graft: the first clinical experience.
AB  - PURPOSE: Aneurysms develop only rarely in aortocoronary saphenous vein grafts
      (SVGs), and the usual treatment is surgical replacement of the diseased segment.
      However, in patients at appreciable risk for redo surgery, alternative therapies
      are desirable. We report the first compassionate use of a percutaneously
      delivered endoluminal graft (ELG) for internal exclusion of an SVG aneurysm.
      METHODS: A 47-year-old male with two coronary bypass procedures and SVG
      angioplasty presented with an 8-mm diameter aneurysm lying between 80% and 70%
      stenotic lesions in an SVG to the obtuse marginal branch. The risks of a third
      bypass operation were considerable, so the decision was made to attempt internal
      exclusion of the SVG aneurysm. RESULTS: An ELG composed of 2.0-mm diameter
      unexpanded PTFE graft material with Palmaz stents for fixation was delivered with
      a low-profile system, but a second ELG was necessary for complete exclusion of
      the aneurysmal sac. Both ELGs were dilated after initial deployment. The patient
      was discharged after 9 days without sequelae, and he remains asymptomatic with
      arteriographically documented ELG patency 5 months after treatment. CONCLUSIONS:
      In this patient with limited therapeutic options, percutaneous aneurysm exclusion
      in an SVG was effective in restoring a viable blood conduit. It remains to be
      seen if ELGs have a potential in aortocoronary SVGs.

PMID- 9234123
TI  - Credentialing criteria for endovascular surgery: report from the Executive Board
      of the International Society for Endovascular Surgery.

PMID- 9234124
TI  - Impact of new technology on vascular surgery training.

PMID- 9234125
TI  - Interaction of regulatory agencies, industry, academic institutions, and the
      practicing physician: impact on technology development and application to medical
      care.

PMID- 9234126
TI  - Aortic aneurysm morphology for planning endovascular aortic grafts: limitations
      of conventional imaging methods.
AB  - PURPOSE: To test whether conventional computed tomography scanning (CT) and
      contrast aortography (CA) provide adequate data for planning endovascular aortic
      grafting by measuring 33 parameters in patients having both imaging examinations
      for evaluation of abdominal aortic aneurysms (AAA). METHODS: Fifty consecutive
      patients with AAA (41 men, 9 women; average age 65 years) had CT and CA (mean 26
      days between exams). The data collected and analyzed included: 8 sites of
      diameter, 4 lengths, 6 angles, and 15 other dimensional measurements. RESULTS:
      Conflicts between CA and CT data were common. Eighteen patients appeared to have
      a distal cuff by CA but not by CT. Proximal neck length could not be assessed by
      CT in 5 and had a difference between CA and CT > 1 cm in 25 patients. CA
      overestimated neck length in 11 patients. Common iliac artery angulation > 60
      degrees unilaterally in 27 patients and bilaterally in 5. Seven patients had both
      iliac aneurysm and > 60 degree iliac angulation. Thirteen patients had one or
      more iliac aneurysms (> 2 cm) shown by CT but not by CA. CONCLUSIONS: For
      endovascular graft planning: (1) more detailed measurement is required than for
      traditional surgery; and (2) conventional CT and CA are complementary imaging
      studies, but each has important limitations.

PMID- 9234127
TI  - Moving beyond conventional.

PMID- 9234128
TI  - Strecker stents in the femoropopliteal arteries: value of duplex ultrasonography
      in restenosis assessment.
AB  - PURPOSE: Experience with Strecker stent implantation in the femoropopliteal
      arteries has been described; however, few of the reports were prospective
      studies, and none routinely used site-specific assessment methods for follow-up
      evaluation of stent patency. The purpose of this study was to evaluate 1-year
      Strecker stent patency using duplex ultrasound imaging to obtain a more precise
      delineation of stent restenosis than is possible with other noninvasive
      assessment modalities. METHODS: A prospective study involved 52 patients with 57
      sites treated by angioplasty and Strecker stent deployment in the femoropopliteal
      arteries. Assessment included clinical evaluation; ankle-brachial index (ABI)
      measurements at rest and after exercise; and duplex ultrasound imaging
      preprocedurally and at 3 and 12 months after the intervention. RESULTS: All 74
      stents were deployed successfully in the 35 occluded arteries and 22 stenotic
      lesions. Acute reocclusion occurred in 6 (10%). At 3 months, primary patency was
      81% and secondary patency 84%. Mean ( +/- SD) ABIs increased from 0.64 +/- 0.15
      at rest and 0.32 +/- 0.17 after exercise to 0.89 +/- 0.14 and 0.68 +/- 0.23,
      respectively (p < 0.0001). At 12 months, primary patency was 79%, and secondary
      patency was 82%. Mean ABIs were 0.82 +/- 0.15 at rest and 0.52 +/- 0.22 after
      exercise at 12 months (p < 0.0002 compared with preprocedural ABIs). Analysis of
      the length of lesion treated showed betted results with shorter diseased
      segments, but this was not statistically significant (p > 0.05). Better outcomes
      were also obtained when one stent was used rather than two stents at 12 months (p
      = 0.15), but there was no difference at 3 months (p = 0.3). Thirty-four percent
      of the stented segments progressed from < 20% stenosis at 3 months to > 50%
      stenosis at 12 months. Overall, 19 (43%) of 44 segments progressed from < 50%
      stenosis at 3 months to a > 50% stenosis at 12 months. Restenosis seen at 3
      months generally was in the native artery just proximal or distal to the stent,
      but at 12 months, restenosis was mainly inside the stent. CONCLUSIONS: Strecker
      stents at 1-year demonstrated satisfactory patency in the femoropopliteal
      arteries when deployed for angioplasty salvage or recurrent disease. The 3- and
      12-month evaluations obtained with duplex ultrasound provided site-specific
      hemodynamic data for stent assessment. Resting ankle pressures were a poor index
      of restenosis.

PMID- 9234129
TI  - Long-term results with the Palmaz stent in the superficial femoral artery.
AB  - PURPOSE: Femoral stenting has demonstrated inconsistent and often disappointing
      long-term results. To compare out experience, we retrospectively analyzed a
      series of patients who had Palmaz balloon-expandable stents placed exclusively
      for superficial femoral artery (SFA) lesions. METHODS: From January 1990 to
      November 1993, 39 patients were evaluated for claudication (79%) or critical
      ischemia in 42 limbs. The culprit lesions were confined to the SFA: 24 (57%)
      occlusions and 18 (43%) stenoses, including 3 restenotic lesions. Stenting was
      elective in 12 (29%) cases: the 3 restenoses and 9 chronic, calcified occlusions.
      The remaining stents were applied for postangioplasty residual stenosis or
      angioscopic findings of thrombogenic luminal irregularities. A total of 55
      prostheses were successfully implanted. All patients were maintained on
      ticlopidine and followed by routine duplex scanning. Follow-up angiography was
      performed in 28 (72%) patients between 4 and 45 months. RESULTS: In the
      postprocedural period, two acute thromboses (4.8%) occurred within 48 hours in
      patients who had long occlusions and poor runoff; no other major complications
      were encountered, for a clinical success rate of 95%. Follow-up evaluation ranged
      from 4 months to 4 years with a mean of 25 months. The restenosis rate was 19%
      (34% in occlusions; 10% in stenotic lesions, p = NS). At 24 months, cumulative
      primary patency was 77% and secondary patency 89%. CONCLUSIONS: Palmaz stents
      performed will in the SFA, demonstrating a low acute thrombosis rate and good
      long-term patency. The incidence of restenosis is likely to be greater in
      occlusions than in stenoses.

PMID- 9234130
TI  - Intraoperative digital subtraction angiography after thromboembolectomy:
      preliminary experience.
AB  - PURPOSE: To evaluate the potential influence of intraoperative digital
      subtraction angiography (DSA) on surgical strategy after balloon
      thromboembolectomy for acute lower limb ischemia. METHODS: Thirty-six consecutive
      patients with critical limb ischemia were treated with balloon catheter
      thromboembolectomy assessed by intraoperative digital subtraction angiography.
      The need for further intervention was determined by the surgeon based on the DSA
      information. Primary completion DSAs were made in every procedure; subsequent
      completion DSAs were performed after reinterventions at the discretion of the
      surgeon. RESULTS: Initial treatment in this patient group consisted of 14
      embolectomies and 26 thrombectomies. From the completion DSAs of these 40
      procedures, a reintervention was judged necessary in 27 (68%). Of these 27
      reinterventions, 17 underwent a secondary DSA; evidence supporting a third
      intervention was found in 11 (64%). Overall, a total of 69 DSAs were performed in
      these patients. Mortality was 22% (8 patients); 38% (5) in embolectomy patients
      and 13% (3) in the thrombectomy cohort. Eighty-eight percent of the embolectomy
      survivors had an uneventful recovery, while only 25% of the thrombectomy
      survivors experienced an uncomplicated follow-up. In one quarter of the surviving
      thrombectomy patients, a surgical revascularization resulted in limb salvage; in
      45%, a major amputation was the outcome. CONCLUSIONS: In this study, the
      completeness of balloon catheter thromboembolectomy was assessed by
      intraoperative DSA. As a result, 68% of the procedures required one or more
      reinterventions for residual lesions. Intraoperative DSA is a simple and quick
      technique that may be a promising adjunct to intraoperative balloon
      thromboembolectomy.

PMID- 9234131
TI  - Transbrachial endovascular exclusion of an axillary artery pseudoaneurysm with
      PTFE-covered stents.
AB  - PURPOSE: Endovascular exclusion of arterial injuries associated with
      arteriovenous fistulas and pseudoaneurysms has only recently been described using
      various stent-graft prostheses. This report details a transbrachial technique
      used to exclude an axillary artery pseudoaneurysm developing at the axillary
      anastomosis of an axillofemoral graft. METHODS AND RESULTS: Thin-walled
      polytetrafluoroethylene was expanded with an angioplasty balloon catheter and
      used to cover standard Palmaz stents. Two covered stents were delivered under
      fluoroscopic guidance via open brachial artery access to the site, resulting in
      complete exclusion of the pseudoaneurysm. Follow-up duplex scanning confirmed
      aneurysm exclusion 3 months postprocedure. CONCLUSIONS: This technique can be
      applied in arteries of different sizes and lengths, using currently available
      materials. However, the long-term behavior of these devices in the arterial tree
      must be determined before their widespread use can be recommended for most
      indications.

PMID- 9234132
TI  - Closure of a popliteal arteriovenous fistula using an autologous vein-covered
      Palmaz stent.
AB  - PURPOSE: To report the use of autologous vein to cover a stainless steel stent
      designated for repair of a traumatic popliteal arteriovenous (AV) fistula.
      METHODS AND RESULTS: Autologous cephalic vein was harvested to cover a Palmaz
      biliary stent selected to close a traumatic popliteal AV fistula that persisted
      despite reparative attempts with balloon occlusion and coil embolization. The
      vein-covered stent was delivered percutaneously and deployed, successfully
      obliterating the vascular communication. Patency of the popliteal artery was
      documented arteriographically at 5 months, and symptomatic improvement continues
      at 10 months. CONCLUSION: The simplicity of this percutaneous approach and the
      use of autologous vein to cover endovascular prostheses create the possibility
      for evaluating this technique in myriad anatomical situations.

PMID- 9234133
TI  - Is natural really better?

PMID- 9234134
TI  - Endovascular techniques in adult aortic coarctation: the use of stents for native
      and recurrent coarctation repair.
AB  - PURPOSE: To report initial experiences with stent implantation in the treatment
      of native and recurrent aortic coarctation in adults. METHODS: Two adult patients
      were diagnosed with aortic coarctation: in one, the native aorta was involved,
      and in the other, the stenosis involved a prior coarctation repair. Both patients
      were offered and selected angioplasty with possible stent implantation as an
      alternative to surgery. RESULTS: In the patient with recurrent narrowing,
      thrombolysis and balloon dilation preceded the successful deployment of three
      Palmaz stents along the grafted segment. In the case of native disease, one
      Palmaz stent was implanted primarily at the site of a critical, focal stenosis.
      No complications were encountered, and recovery was uneventful. Follow-up at 12
      and 6 months, respectively, showed sustained clinical improvement with resolution
      of symptoms and excellent hemodynamic values. CONCLUSIONS: The positive outcome
      in these early cases supports further evaluation of the efficacy of adjunctive or
      primary stenting for treatment of native or recurrent aortic coarctation in
      adults.

PMID- 9234135
TI  - Endovascular repair of an ascending aorta-to-left common femoral artery graft
      with aneurysmal degeneration.
AB  - PURPOSE: To report the use of endovascular grafting to repair degenerative
      aneurysmal changes in an extra-anatomic bypass graft. METHODS: A 14-year-old
      extra-anatomic ascending aorta-to-left common femoral bypass graft ("ventral
      aorta") had undergone aneurysmal degeneration, producing symptoms of progressive
      claudication and local abdominal swelling. The aneurysmal graft dilatation began
      within the thoracic cavity and extended through the entire extraperitoneal
      abdominal segment. The option for minimally invasive repair using a customized
      stent-graft device was offered to the patient as an alternative to standard
      reoperation. RESULTS: An 8-mm x 42-cm endovascular graft was constructed by
      polytetrafluoroethylene with 30-mm Palmaz stents sutured to each end. With
      balloon occlusion of antegrade and retrograde blood flow, the stent-graft was
      delivered retrograde through an incision in the distal end of the existing bypass
      graft. The device was successfully positioned and deployed with complete
      exclusion of the aneurysm. No complications occurred, and the patient's symptoms
      abated. Follow-up arteriography at 1 months showed a pseudoaneurysm at the distal
      graft incision site; surgical repair was necessary. At 6 months, angiography
      demonstrated continued patency of the extra-anatomic bypass graft. CONCLUSIONS:
      Intraluminal aneurysm exclusion techniques in degenerated extra-anatomic bypass
      grafts may evolve into a viable therapeutic alternative to complex reoperative
      surgery.

PMID- 9234136
TI  - Endovascular surgery and its effect on the relationship between vascular surgery
      and radiology.

PMID- 9234137
TI  - Endoluminal grafting for aneurysmal and occlusive disease in the superficial
      femoral artery: early experience.
AB  - PURPOSE: To examine whether endoluminal grafts (ELGs) of radically expandable
      polytetrafluoroethylene (PTFE) can successfully form durable internal conduits to
      revascularize lengthy occlusive disease and exclude aneurysms in the
      femoropopliteal (FP) arteries. METHODS: Under protocol, implantation of an
      unpredilated PTFE tube ELG anchored with Palmaz stents using a low-profile
      percutaneous delivery system was attempted in 50 symptomatic patients for a
      variety of pathologies: (1) restenosis; (2) complex lesions unlikely to be
      treated successfully with other endoluminal therapies; (3) acute angioplasty
      failure; and (4) aneurysms. There were 37 occlusions, 14 stenoses, and 2 long,
      combined stenotic-aneurysmal lesions in 47 native arteries, 5 FP grafts, and 1
      femorotibial (FT) vein graft. Thirty-two percent of the patients had < or =
      vessel runoff. The average lesion length was 20.4 +/- 11.4 cm (range 1.5 to 40),
      and the mean preoperative ankle-brachial index (ABI) at rest was 0.53 +/- 0.14.
      RESULTS: In a 20-month period through April 1995, 50 patients (34 males, 16
      females; mean age 69.5 years, range 45 to 87) underwent 54 procedures in 53
      limbs; 55 ELGs were successfully deployed in 51 limbs; 2 patients were converted
      to FP bypass owing to technical problems (96% procedural success). There were 18
      inhospital complications: 1 distal wire dissection repaired with an additional
      ELG; 2 hematomas requiring surgical repair; 1 graft collapse; 1 pseudoaneurysm at
      the site of a mid-ELG leak; 7 minor access sequelae; and 6 acute ELG thromboses,
      4 treated with lytic therapy and balloon dilation, 1 with open thrombectomy, and
      1 with bypass grafting. The mean postoperative ABI was 1.01 +/- 0.10. During the
      30-day postprocedure period, 2 ELGs rethrombosed and 2 other limbs (3 ELGs)
      occluded; 1 thrombosis and 1 rethrombosis were lysed successfully, but the other
      2 patients had an FP bypass. Over the mean 8.3 +/- 5.5 month follow-up, 6
      additional ELGs occluded and 1 reoccluded; 4 were successfully treated by
      endovascular techniques for a primary patency of 72% and secondary patency of 84%
      by life-table analysis. CONCLUSIONS: Endovascular grafting is a conceptually
      attractive technique that has the potential to expand the current boundaries of
      interventional treatment. This preliminary experience attests to the feasibility
      and safety of ELG deployment in the superficial femoral arteries. Whether such a
      device can match the durability of classical revascularization techniques remains
      to be determined in clinical trials when device configurations and deployment
      techniques have been standardized.

PMID- 9234138
TI  - Early experience with the Sydney and EVT prostheses for endoluminal treatment of
      abdominal aortic aneurysms.
AB  - PURPOSE: The aim of this study was to report early experiences with the Sydney
      and Endovascular Technologies (EVT) prostheses for the treatment of abdominal
      aortic aneurysms (AAA) deemed suitable for endoluminal tube graft repair.
      METHODS: Consecutive endoluminal tube graft repairs were analyzed over the first
      12 months in which the Sydney and EVT prostheses were used. Patients eligible for
      the EVT prosthesis had type I AAAs: a proximal neck length > or = 2 cm, a distal
      cuff length > or = 1.5 cm, and nontortuous iliac arteries > or = 8 mm. Selection
      criteria for the Sydney device were more liberal and included AAAs that had
      distal cuffs < 1.5 cm. During the study period, 28 of 91 patients evaluated for
      AAA repair were thus selected for endoluminal grafting: 18 patients received the
      Sydney endograft and 10 the EVT device. Medical comorbidities were present in
      slightly less than one third of patients in both groups. Contrast-enhanced
      computerized tomography (CT) was performed preoperatively, within 10 days of
      operation, and at 6 and 12 months postprocedure. RESULTS: All endografts were
      successfully deployed in both groups. Postprocedural CT scans revealed incomplete
      aneurysm exclusion in four patients with the Sydney endograft. Subsequent
      deployment of a second endograft sealed these "leaks" in two cases; the other two
      were converted to open repair (89% clinical success). No leaks were seen with the
      EVT device. Local/vascular complications occurred in 33% of the Sydney group
      compared with 20% for the EVT device (p = 0.001); systemic sequelae were more
      common in the EVT group (30% versus 17% in the Sydney cohort, p = 0.002). There
      were no deaths within 30 days; three late deaths were not procedure related.
      CONCLUSION: AAAs that are suitable for endoluminal tube graft repair may be
      treated with a high rate of initial success with either the Sydney or EVT
      prostheses. More liberal selection criteria may increase the likelihood of
      local/vascular complications.

PMID- 9234139
TI  - Angioscopic evaluation of an endoluminal aortic graft: the first clinical
      experience.
AB  - PURPOSE: Balloon aortoscopy has been described for viewing aortic endoluminal
      anatomy and guiding aortic stent placement in animals. We report the first
      clinical use of this technique to visually inspect the proximal portion of a 1
      year-old endovascular aortic graft, its proximal fixation stent, and its
      relationship to the renal arteries. METHODS: The aortoscope is a modified fiber
      optic endoscope that is fitted over the lens with a transparent, saline-filled
      balloon for blood displacement. Its performance was evaluated in a 62-year-old
      woman who had a Parodi-type Dacron/modified Palmaz stent endoluminal graft
      implanted to exclude an infrarenal aortic aneurysm in 1994. One year later,
      during an angioplasty procedure for symptomatic left subclavian and left common
      iliac artery stenoses, the 1-year-old endoluminal graft was inspected with the
      balloon-tipped angioscopic assembly. RESULTS: Introduced via the left brachial
      artery, the aortoscope provided a panoramic view of the endoluminal surface
      through the solution-filled balloon. The endoluminal aortic graft was clearly
      identified, as were both renal artery orifices proximal to the graft. The surface
      of the proximal stent was smooth and without exposed metal. No complications
      occurred with the angioscopy technique. CONCLUSIONS: Aortic angioscopy can be
      used to evaluate endoluminal aortic grafts and endoluminal anatomy. It provides
      clear, magnified views that may be useful for guiding precise placement and
      assessing the function and healing of endoluminal devices in the aorta.

PMID- 9234140
TI  - Use of polyetherurethane to improve the biocompatibility of vascular stents.
AB  - PURPOSE: To investigate potential differential growth on neointima following
      overdilating arterial trauma with polyetherurethane-coated versus bare metallic
      stents in swine. METHODS: Twelve specially constructed tantalum stents, 6 coated
      with polyetherurethane block copolymer and 6 uncoated, were overdilated by 25% in
      12 normal renal arteries of six swine. The stents were harvested 8 weeks after
      implantation and prepared for histologic examination. Neointimal thickness was
      quantified and analyzed for significant differences between coated and uncoated
      prostheses. RESULTS: All specimens demonstrated fractures of the internal elastic
      lamina consistent with vascular injury. There was significantly less neointimal
      formation (0.0001 < p < 0.05) in coated specimens as compared to uncoated
      controls in each test animal. CONCLUSIONS: The vascular response to overdilating
      stent trauma appears to be moderated with the use of polyetherurethane block
      copolymer as compared to control.

PMID- 9234141
TI  - Polymeric covers and coats for metallic stents: microporous PTFE and the
      inhibition of intimal hyperplasia.

PMID- 9234142
TI  - Magnetic resonance acquisition to determine the lumen length of a tortuous
      phantom aorta.
AB  - PURPOSE: Endovascular abdominal aortic aneurysm repair is a technique that
      requires an accurate measurement of the aneurysm's lumen length prior to the
      procedure. This study examines the accuracy of luminal length measurement in an
      aortic phantom using magnetic resonance angiography (MRA) axial source images.
      METHODS AND RESULTS: Tortuous phantom aortas were constructed using water-filled
      plastic tubing (7 mm in diameter with lengths of 80 to 160 mm). The tubes were
      molded into three-dimensional "S" or "C" shapes that simulated the luminal course
      of a tortuous aorta. Phantoms were imaged at angles of 0 degrees, 15 degrees, 30
      degrees, and 45 degrees to the image slice direction on a 1.5T Signa MR scanner
      using a transaxial two-dimensional time-of-flight (TOF) and a T1-weighted spin
      echo acquisition. The luminal length of the phantom was calculated after
      establishing the lumen center coordinates in axial source images and then
      measuring the distance between two sequential slices using the Pythagorean
      theorem. The accuracy of this measurement in the phantom was 89% to 99.6%,
      proportional to the length of the tubing. Accuracy was not affected by angulation
      of < 45 degrees. CONCLUSION: Two-dimensional TOF MRA source images can provide an
      accurate measurement of the phantom aorta's lumen length.

PMID- 9234144
TI  - Oceans apart: the dichotomy in superficial femoral endarterectomy.

PMID- 9234143
TI  - The Mollring Cutter remote endarterectomy: preliminary experience with a new
      endovascular technique for treatment of occlusive superficial femoral artery
      disease.
AB  - PURPOSE: To evaluate the feasibility and efficacy of the Mollring Cutter remote
      endarterectomy (EA) technique in the treatment of occlusive superficial femoral
      artery (SFA) disease. METHODS: A new device was developed to perform remote EA of
      occluded SFAs through a single groin incision. The technique initially uses a
      conventional ring stripper, which is exchanged for a double-ring cutter that
      transects the distal atheroma core. The entire core and cutter are removed
      simultaneously, and a Palmaz stent is implanted to secure the distal intimal
      flap. RESULTS: Twenty-six consecutive patients with disabling claudication or
      critical ischemia were treated for long segment occlusions (n = 23) and multiple
      stenoses (n = 3). Patients were evaluated on the intention-to-treat basis.
      Clinical and anatomic success was achieved in all 26 SFAs. Average length of the
      endarterectomized segments was 29.9 cm (range 23 to 41). Technical problems were
      encountered intraoperatively in four patients, including one who required a
      second incision at the distal SFA to retrieve a broken ring. Recovery was
      uneventful in all patients. At up to 6-month follow-up, one reocclusion has been
      seen at 5 months. CONCLUSION: Based on this early experience, remote EA with the
      Mollring Cutter appears to be feasible and effective method for treating
      occlusive SFA disease. Obviating the need for a second incision at knee level,
      this technique offers a less invasive approach that should facilitate
      postoperative recovery and earlier discharge.

PMID- 9234145
TI  - A new access site management tool: the Angio-Seal hemostatic puncture closure
      device.
AB  - PURPOSE: Given the increasing number of percutaneously applied endovascular
      therapies, the incidence of access-related vascular complications can be expected
      to rise, particularly in association with those techniques requiring large
      sheaths or anticoagulation. The need exists for a safe, easy to use, and
      effective hemostatic technique to replace the labor-intensive method of manual
      compression. METHODS: A bioabsorbable, sheath-delivered vascular device (Angio
      Seal) has been developed that deposits a small collagen plug within the arterial
      wall to mechanically seal the puncture defect. An anchor connected by suture to
      the plug is first deployed in the arterial lumen and pulled flush against the
      interior wall to guard against intraluminal deposition of the collagen. RESULTS:
      The Angio-Seal device was deployed successfully in 80 (96%) of 83 attempts
      involving common femoral arteries accessed for peripheral angioplasty (n = 30),
      coronary angiography (n = 30), and coronary angioplasty (n = 16). Three popliteal
      artery access sites and one femoropopliteal bypass graft were also treated.
      Hemostasis was immediate in 78 cases (98%); 2 sites required a 5-minute manual
      compression to effect a secure seal. Three devices failed to deploy, and manual
      pressure was used to close the puncture. Nondeployment did not cause any
      sequelae, and no complications were encountered with the technique. CONCLUSIONS:
      This novel vascular closure device is quick (< 1 minute application time) and
      simple to use, providing a positive seal of common femoral artery puncture sites
      for both peripheral and coronary interventions. It appears to be a reliable
      alternative to standard manual hemostasis.

PMID- 9234146
TI  - Superficial femoral endarterectomy with intra-arterial PTFE grafting.
AB  - PURPOSE: To report early experience with a new endovascular approach to treating
      occluded Wallstents in the superficial femoral artery (SFA). METHODS AND RESULTS:
      A symptomatic female patient with a 20-cm SFA occlusion involving a 10-cm
      Wallstent placed 2 years previously was offered an endovascular intervention.
      However, when percutaneous recanalization techniques failed, a semiclosed
      endarterectomy was undertaken using a conventional ring stripper. Although the
      atherosclerotic core and stent were removed smoothly, a small perforation was
      seen in the distal SFA. To avoid surgical repair, the endarterectomized segment
      was lined endoluminally using a 3-mm diameter, thin-walled
      polytetrafluoroethylene graft. A 15-mm Palmaz stent was used for distal fixation,
      with a plasty procedure performed at the proximal arteriotomy. There were no
      postoperative complications, and the patient, who was discharged on the second
      day, remains asymptomatic with normal flow through the graft at 3 months.
      CONCLUSION: Newer endovascular techniques may be applied in concert with
      conventional semiclosed endarterectomy to successfully treat lengthy SFA
      occlusions, particularly those involving stents.

PMID- 9234147
TI  - Infrainguinal atherectomy using the Auth Rotablator.

PMID- 9234149
TI  - Revising the reporting guidelines: how far do we need to go?

PMID- 9234148
TI  - Reporting guidelines for open and endovascular surgery: why the current
      recommendations should be revised.

PMID- 9234150
TI  - Can there really be "uniform" reporting guidelines?

PMID- 9234151
TI  - Reporting guidelines: another perspective.
AB  - The following data are required when reporting results of a procedure for
      occlusive disease of the lower limb: (1) PREOPERATIVE PATIENT ASSESSMENT: This
      should include age, sex, diabetes, smoking habit, whether the ischemic symptoms
      are at rest or after exercise, and the resting ankle or toe pressure. (2)
      INTENTION TO TREAT: This should be stated as a percentage of the number of
      procedures that actually were properly performed against the number of procedures
      scheduled. Only those procedures that were performed should be subsequently
      analyzed. (3) ACUTE RESULTS: This is assessed by an imaging technique, such as
      angiography or duplex ultrasound, and defined in terms of patency and degree of
      maximal stenosis in the area treated and 5 cm on either side. Change in symptoms,
      complications, and ankle pressures should be reported but are not criteria for
      procedural success or failure. The assessment should be done from 10 to 30 days
      following the procedure. (4) LONG-TERM RESULTS: As assessed by appropriate
      imaging techniques, outcome should be reported in terms of primary, assisted
      primary, and secondary patency. The degree of maximal stenosis in the treated
      segments and 5 cm on either side should be stated. The surveillance intervals
      would depend on the answers being sought in the follow-up period, but the minimum
      would be an annual review. Three-year results are required to give an adequate
      assessment of the durability of a procedure. (5) REPORTING: Life-table analysis
      should be used to present the data on patencies and the degree of stenosis.

PMID- 9234152
TI  - Challenges facing European vascular surgeons.

PMID- 9234153
TI  - A prospective study of changes in morphology and dimensions of abdominal aortic
      aneurysms following endoluminal repair: a preliminary report.
AB  - PURPOSE: The aim of this prospective study was to analyze early changes in
      morphology and dimensions of abdominal aortic aneurysms (AAA) following
      endoluminal repair. METHODS: Forty-two of 62 patients undergoing endoluminal
      repair of AAAs between May 1992 and November 1994 were potentially available for
      follow-up at 6 months or longer after operation. After excluding patients with
      failed endoluminal repairs, patients who died within 6 months of operation, and
      patients with anastomotic aneurysms, a study group of 30 patients remained.
      Contrast-enhanced computed tomography (CE-CT) was performed preoperatively,
      within 10 days of operation, and at 6 and 12 months postprocedure. Based on the
      postoperative CE-CT findings, patients were divided into two groups: those with
      no extravasation of contrast into the aneurysmal sac (group I; n = 26), and those
      in which there was contrast extravasation ("leak") into the aneurysmal sac (group
      II; n = 4). RESULTS: The mean maximum diameters of AAAs in group I diminished
      progressively at 6 and 12 months, while those in group II increased. Twenty-three
      (88%) patients in group I had decreased diameter of AAA, while all patients in
      group II had progressive increase in AAA diameter. Patients who had an increase
      in AAA diameter had a significantly higher incidence of leak compared with those
      who had a decrease in diameter (p = 0.001). CONCLUSIONS: The majority of AAAs in
      which the sac has been excluded from the general circulation diminish in size
      following successful endoluminal repair. An increase in size occurs in those AAAs
      in which a communication exists between the aortic lumen and the sac. These
      results suggest that successfully excluded AAAs that continue to increase in size
      should be suspected of having an undetected leak.

PMID- 9234154
TI  - Results of autopsy 7 months after successful endoluminal treatment of an
      infrarenal abdominal aortic aneurysm.
AB  - PURPOSE: To report the results of a postmortem examination in a patient who died
      of unrelated causes 7 months following endoluminal treatment of an infrarenal
      abdominal aortic aneurysm (AAA). METHODS: As part of an FDA Phase I pilot study,
      a 73-year-old man underwent successful endoluminal exclusion of an infrarenal AAA
      using a 9-cm-long endograft (Endovascular Grafting System). Seven months later,
      he succumbed to complications of a spontaneous esophageal rupture. At autopsy,
      the aorta was dissected in situ by a vascular surgeon and pathologist before
      being explanted in order to examine the wound healing characteristics at the
      aorta-endograft interface. Particular attention was also directed to the hooks
      composing the attachment system at each end of the endograft. RESULTS:
      Macroscopic and microscopic examination revealed that the graft had completely
      excluded the aneurysm sac from the circulation and was incorporated into the
      aortic wall at the proximal neck and distal cuff. A smooth pannus of endothelial
      cells covered the proximal end of the endograft at the areas of contact with the
      aorta, while microscopic examination of the distal end of the graft revealed
      poorly formed, fibrinous pannus. The neointima deep to the endothelium consisted
      of a collagenous matrix containing myofibroblasts and histiocytes, providing
      evidence of healing between the endograft and aorta. Both renal arteries were
      clear of the proximal end of the endograft, but a previously unrecognized right
      lower pole renal artery with an extremely caudal origin was excluded from the
      aortic lumen. Each hook of the attachment system was seen protruding through the
      adventitia of the aorta. There was no evidence of trauma to the aortic wall or
      the surrounding tissues caused by these hooks. CONCLUSION: There appears to be
      evidence that an endoluminally placed aortic graft may be incorporated by the
      host aortic tissue.

PMID- 9234155
TI  - The clinical value of three-dimensional intravascular ultrasound imaging.
AB  - Two-dimensional (2D) intravascular ultrasound (IVUS) imaging can now be
      reconstructed into three dimensions from serial 2D images captured following a
      "pullback" of the IVUS catheter through the target site. Three-dimensional (3D)
      reconstructions provide "longitudinal" and "volume" images. The former is similar
      to an angiogram and can be examined in three dimensions by rotating the image
      around its longitudinal axis, providing clinically useful information during
      endovascular procedures. The volume view takes longer to create and is not an
      exact reconstruction, but it provides images that can be rotated into any spatial
      position. It visualizes the luminal aspect of the vessel particularly well. The
      clinical value of 3D IVUS is in the diagnosis of vascular disease and the
      assessment of endovascular interventions. Three-dimensional IVUS, which provides
      better, more informative images than 2D IVUS, can be particularly useful
      intraprocedurally in detecting inaccurate deployment of intravascular stents and
      endoluminal grafts.

PMID- 9234156
TI  - Determining light dose for photodynamic therapy of atherosclerotic lesions in the
      Yucatan miniswine.
AB  - PURPOSE: To determine the light dose required for photodynamic therapy of
      atherosclerotic lesions in the miniswine. METHODS: Aortic atherosclerosis was
      created in seven Yucatan miniswine by a combination of balloon endothelial injury
      and 2% cholesterol and 15% lard for 7 weeks. Six animals received the
      photosensitizer Photofrin 2.5 mg/kg, while an additional swine received no drug.
      After 24 hours, the abdominal aorta was exposed and the aorta opened
      longitudinally in each animal. Three 1-cm spots were illuminated with energy
      densities of 60, 120, and 240 J/cm2 from an argon-pumped dye laser tuned to 630
      nm with a laser output of 1 W. Four weeks later, the animals were killed,
      abdominal aortae removed, and intimal thickness determined by morphometry.
      RESULTS: The percentage intimal thickness (mean +/- SD) was 36.7 +/- 27.1, 9.1 +/
      5.0, and 6.4 +/- 8.1 for the three energy densities, respectively. Although both
      120 and 240 J/cm2 energy densities produced significant (p < 0.05) reduction in
      atheroma, considerable damage to the underlying media was also observed in the
      240 J/cm2 group. CONCLUSIONS: A Photofrin dose of 2.5 mg/kg and 120 J/cm2 light
      are necessary for adequate ablation of atheroma while avoiding extensive medial
      damage.

PMID- 9234158
TI  - From the board meeting: more like war than peace!

PMID- 9234157
TI  - Bird's nest inferior vena caval filter migration into the duodenum: a rare cause
      of upper gastrointestinal bleeding.
AB  - PURPOSE: To report the first case of a potentially catastrophic complication of
      vena caval interruption with a bird's nest filter. METHODS AND RESULTS: A 55-year
      old Saudi patient presented with hypovolemic shock from massive upper
      gastrointestinal hemorrhage. Endoscopy identified a metallic object penetrating
      the duodenum. Five years earlier, the patient had a bird's nest vena caval filter
      inserted for recurrent pulmonary embolism. During emergent laparotomy, a broken
      filter wire was found projecting into the duodenum, where it had induced three
      profusely bleeding ulcers. The wire was transected and the ulcers oversewn. A
      hook projecting from the inferior vena cava (IVC) was also cut flush with the
      vessel wall, but the IVC was not opened nor the filter replaced. The patient's
      postoperative course was complicated by deep venous thrombosis, but he recovered
      and is asymptomatic on warfarin anticoagulation after 1 year. Computed tomography
      (CT) at 1-year follow-up confirmed no further migration of the filter.
      CONCLUSION: This event reinforces the need to monitor patients with IVC filters
      over the long term, preferably using CT scanning, and to consider filter
      migration as a possible cause of upper gastrointestinal bleeding.

PMID- 9234159
TI  - Alkaloids from endophyte-infected Festuca argentina.
AB  - Five loline-type alkaloids, the known lolinine, N-formylloline, loline, N
      methylloline and the new 5,6-dehydro-N-acetylloline, were characterized from the
      pooid-grass endophyte-infected Festuca argentina. These compounds are not
      responsible for the toxicity of the plant, as shown upon i.p. injection into
      mice. Their probable phytoalexine role and chemotaxonomical significance are
      discussed.

PMID- 9234160
TI  - Behavioural effects of Passiflora incarnata L. and its indole alkaloid and
      flavonoid derivatives and maltol in the mouse.
AB  - Lyophilised hydroalcoholic and aqueous extracts of the aerial parts of Passiflora
      incarnata L. (Passifloraceae) (Passion-flower), as well as chemical constituents
      of the plant, indole alkaloids (harman, harmin, harmalin, harmol, and harmalol)
      maltol and flavonoids (orientin, isoorientin, vitexin and isovitexin) were
      assessed for behavioral effects in mice. The accordance with the traditional use
      of P. incarnata, psychotropic properties were confirmed by some behavioral tests
      in mice. The anxiolytic properties of hydroalcoholic extract were confirmed at
      400 mg/kg by the increase of rears and steps climbed in the staircase test (non
      familiar environmental test), and the increase in locomotion and time spent in
      light side in the light/dark box choice test (non-familiar environmental test).
      The sedative properties of aqueous extract were confirmed at 400 g/kg by decrease
      of rears and steps climbed in the staircase test and the decrease of rears and
      locomotion in the free exploratory test. Moreover, the aqueous extract induced
      sleep in mice after treatment with a sub-hypnotic dose of pentobarbital.

PMID- 9234161
TI  - Aphrodisiac property of Trichopus zeylanicus extract in male mice.
AB  - Administration of Trichopus zeylanicus leaf (ethanol extract) to male mice
      stimulated their sexual behaviour as evidenced by an increase in number of mounts
      and mating performance. This activity of the ethanol extract was concentration
      dependent and destroyed by heat treatment at 100 degrees C for 15 min. Although
      oral administration of a single dose (200 mg/kg) was effective, daily
      administration of the extract for 6 days was found to be more effective. The pups
      fathered by the drug treated mice were found to be normal with reference to
      foetal growth, litter size and sex ratio. The water as well as n-hexane extracts
      of the plant leaf were inactive. The present study reveals for the first time the
      aphrodisiac activity of Trichopus zeylanicus, an endemic herb of India.

PMID- 9234162
TI  - Antifungal activity and kinetics of inhibition by essential oil isolated from
      leaves of Aegle marmelos.
AB  - The antifungal activity of essential oil isolated from the leaves of bael (Aegle
      marmelos (L.) Correa ex Roxb., Rutaceae) has been evaluated using spore
      germination assay. The oil exhibited variable efficacy against different fungal
      isolates and 100% inhibition of spore germination of all the fungi tested was
      observed at 500 ppm. However, the most resistant fungus, Fusarium udum was
      inhibited 80% at 400 ppm. Kinetic studies showed concentration as well as time
      dependent complex inhibition of spore germination by the essential oil.

PMID- 9234163
TI  - Evaluation of some Samoan and Peruvian medicinal plants by prostaglandin
      biosynthesis and rat ear oedema assays.
AB  - In our ongoing program to find new anti-inflammatory compounds, 58 extracts from
      46 different medicinal plant species, used in treatment of inflammatory disorders
      38 plants from the traditional medicine of Western Samoa and eight originating
      from the indigenous medicine of the Shipibo-Conibo tribe of Peruvian Amazonia-ere
      evaluated. The ability of all extracts to inhibit cyclooxygenase-1 catalysed
      prostaglandin biosynthesis in vitro was examined. Of the plant species tested 14
      showed moderate to strong inhibition; including 11 Samoan and three Peruvian
      species. Further, 12 Samoan and all eight Peruvian species were investigated on
      their inhibitory activity of ethyl phenylpropiolate induced rat ear oedema in
      vivo. Significant activity was shown by 10 of the Samoan and by all eight
      Peruvian species. An additional evaluation of the most active species was
      provided through a compilation of existing literature documenting traditional
      medicinal uses, pharmacological activity and chemical constituents. Several known
      cyclooxygenase-1 inhibitors were reported to which the observed pharmacological
      activity can be attributed at least partly. The combination of chemical and
      pharmacological literature data and our experimental data may help to explain the
      anti-inflammatory use of these species in indigenous medicine.

PMID- 9234164
TI  - Spasmolytic effect of water extract of Stemonae radix on the guinea-pig tracheal
      smooth muscle in vitro.
AB  - The present study examined the relaxing effect of a water extract of Baibu
      (Stemonae radix, the root tuber of Semona sessilifolia (Miq.) Franch. et Sav.) on
      carbachol-, histamine- and KCl-induced contractions of the guinea-pig isolated
      tracheal preparations. The results showed that Baibu (1-50 mg/ml) concentration
      dependently relaxed the tracheal preparations contracted by these spasmogens with
      an IC50 value (mg/ml) of 2.0 +/- 0.1 for carbachol, 41.2 +/- 0.8 for histamine
      and 18.6 +/- 0.9 for KCl. The effect of Baibu was not affected by the
      pretreatment with a beta-adrenoceptor antagonist propranolol (10(-6) M),
      indicating that Baibu's effect was not due to an activation on beta
      adrenoceptors. Baibu shifted the concentration-response curve of carbachol to the
      right in a parallel manner without changing the maximal response, having a pA2
      value of 0.16 +/- 0.07 mg/ml (equivalent to a KB = 0.70 +/- 0.11 mg/ml). This
      indicates a competitive antagonism at the muscarinic receptors. Receptor binding
      assay indicated that Baibu interacted with the muscarinic receptors (Ki = 0.51 +/
      0.12 mg/ml) and the dihydropyridine (DHP) binding site of L-type Ca2+ channels
      (Ki = 8.0 +/- 1.9 mg/ml), but not with the histamine H1 receptors. Therefore, the
      present study demonstrates that Baibu contains the principle(s) acting on the
      muscarinic receptors and DHP binding sites, which contribute its relaxation
      effect on the airway smooth muscles.

PMID- 9234165
TI  - Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1 beta-
      and tumor necrosis factor alpha-induced adhesion molecule expression in cultured
      human umbilical vein endothelial cells.
AB  - We examined the effects of nine flavonoids isolated from Scutellariae radix on
      interleukin-1 beta (IL-1 beta)- and tumor necrosis factor-alpha (TNF-alpha)
      induced adhesion molecule expression in cultured human umbilical vein endothelial
      cells (HUVECs). Among them, we found that baicalein (5,6,7-trihydroxy flavone)
      dose-dependently inhibited IL-1 beta and TNF-alpha-induced endothelial leukocyte
      adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1)
      expressions. Its 50% inhibitory concentrations (IC50) for the IL-1 beta-induced
      ELAM-1 and ICAM-1 expressions were 2.3 x 10(-5) M and 4.0 x 10(-5) M,
      respectively. The IC50 for the TNF-alpha-induced ELAM-1 and ICAM-1 expressions
      were 1.5 x 10(-5) M and 3.1 x 10(-5) M, respectively. In addition, protein C
      kinase (PKC) inhibitor H7 also inhibited the ELAM-1 and ICAM-1 expressions
      induced by IL-1 beta and TNF-alpha.

PMID- 9234166
TI  - The secretion-coupled endocytosis correlates with membrane tension changes in RBL
      2H3 cells.
AB  - Stimulated secretion in endocrine cells and neuronal synapses causes a rise in
      endocytosis rates to recover the added membrane. The endocytic process involves
      the mechanical deformation of the membrane to produce an invagination. Studies of
      osmotic swelling effects on endocytosis indicate that the increased surface
      tension is tightly correlated to a significant decrease of endocytosis. When rat
      basophilic leukemia (RBL) cells are stimulated to secrete, there is a dramatic
      drop in the membrane tension and only small changes in membrane bending
      stiffness. Neither the shape change that normally accompanies secretion nor the
      binding of ligand without secretion causes a drop in tension. Further, tension
      decreases within 6 s, preceding shape change and measurable changes in
      endocytosis. After secretion stops, tension recovers. On the basis of these
      results we suggest that the physical parameter of membrane tension is a major
      regulator of endocytic rate in RBL cells. Low tensions would stimulate
      endocytosis and high tensions would stall the endocytic machinery.

PMID- 9234167
TI  - Anomalous effect of permeant ion concentration on peak open probability of
      cardiac Na+ channels.
AB  - Human heart Na+ channels were expressed transiently in both mammalian cells and
      Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+.
      Decreasing extracellular permeant ion concentration decreases outward Na+ current
      at positive voltages while increasing the driving force for the current. This
      anomalous effect of permeant ion concentration, especially obvious in a mutant
      (F1485Q) in which fast inactivation is partially abolished, is due to an
      alteration of open probability. The effect is only observed when a highly
      permeant cation (Na+, Li+, or hydrazinium) is substituted for a relatively
      impermeant cation (K+, Rb+, Cs+, N-methylglucamine, Tris, choline, or
      tetramethylammonium). With high concentrations of extracellular permeant cations,
      the peak open probability of Na+ channels increases with depolarization and then
      saturates at positive voltages. By contrast, with low concentrations of permeant
      ions, the open probability reaches a maximum at approximately 0 mV and then
      decreases with further depolarization. There is little effect of permeant ion
      concentration on activation kinetics at depolarized voltages. Furthermore, the
      lowered open probability caused by a brief depolarization to +60 mV recovers
      within 5 ms upon repolarization to -140 mV, indicative of a gating process with
      rapid kinetics. Tail currents at reduced temperatures reveal the rapid onset of
      this gating process during a large depolarization. A large depolarization may
      drive a permeant cation out of a site within the extracellular mouth of the pore,
      reducing the efficiency with which the channel opens.

PMID- 9234168
TI  - Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.
AB  - Human heart Na+ channels were expressed transiently in both mammalian cells and
      Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+. The
      kinetics of decaying outward Na+ current in response to 1-s depolarizations in
      the F1485Q mutant depends on the predominant cation in the extracellular
      solution, suggesting an effect on slow inactivation. The decay rate is lower for
      the alkali metal cations Li+, Na+, K+, Rb+, and Cs+ than for the organic cations
      Tris, tetramethylammonium, N-methylglucamine, and choline. In whole cell
      recordings, raising [Na+]zero from 10 to 150 mM increases the rate of recovery
      from slow inactivation at -140 mV, decreases the rate of slow inactivation at
      relatively depolarized voltages, and shifts steady-state slow inactivation in a
      depolarized direction. Single channel recordings of F1485Q show a decrease in the
      number of blank (i.e., null) records when [Na+]0 is increased. Significant
      clustering of blank records when depolarizing at a frequency of 0.5 Hz suggests
      that periods of inactivity represent the sojourn of a channel in a slow
      inactivated state. Examination of the single channel kinetics at +60 mV during 90
      ms depolarizations shows that neither open time, closed time, nor first latency
      is significantly affected by [Na+]0. However raising [Na+]0 decreases the
      duration of the last closed interval terminated by the end of the depolarization,
      leading to an increased number of openings at the depolarized voltage. Analysis
      of single channel data indicates that at a depolarized voltage a single rate
      constant for entry into a slow-inactivated state is reduced in high [Na+]0,
      suggesting that the binding of an alkali metal cation, perhaps in the ion
      conducting pore, inhibits the closing of the slow inactivation gate.

PMID- 9234169
TI  - Redox regulation of large conductance Ca(2+)-activated K+ channels in smooth
      muscle cells.
AB  - The effects of sulfhydryl reduction/oxidation on the gating of large-conductance,
      Ca(2+)-activated K+ (maxi-K) channels were examined in excised patches from
      tracheal myocytes. Channel activity was modified by sulfhydryl redox agents
      applied to the cytosolic surface, but not the extracellular surface, of membrane
      patches. Sulfhydryl reducing agents dithiothreitol, beta-mercaptoethanol, and GSH
      augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2'
      dithiodipyridine inhibited, channel activity in a concentration-dependent manner.
      Channel stimulation by reduction and inhibition by oxidation persisted following
      washout of the compounds, but the effects of reduction were reversed by
      subsequent oxidation, and vice versa. The thiol-specific reagents N
      ethylmaleimide and (2-aminoethyl)methanethiosulfonate inhibited channel activity
      and prevented the effect of subsequent sulfhydryl oxidation. Measurements of
      macroscopic currents in inside-out patches indicate that reduction only shifted
      the voltage/nP0 relationship without an effect on the maximum conductance of the
      patch, suggesting that the increase in nP0 following reduction did not result
      from recruitment of more functional channels but rather from changes of channel
      gating. We conclude that redox modulation of cysteine thiol groups, which
      probably involves thiol/disulfide exchange, alters maxi-K channel gating, and
      that this modulation likely affects channel activity under physiological
      conditions.

PMID- 9234171
TI  - P-loop flexibility in Na+ channel pores revealed by single- and double-cysteine
      replacements.
AB  - Replacement of individual P-loop residues with cysteines in rat skeletal muscle
      Na+ channels (SkM1) caused an increased sensitivity to current blockade by Cd2+
      thus allowing detection of residues lining the pore. Simultaneous replacement of
      two residues in distinct P-loops created channels with enhanced and reduced
      sensitivity to Cd2+ block relative to the individual single mutants, suggesting
      coordinated Cd2+ binding and cross-linking by the inserted sulfhydryl pairs.
      Double-mutant channels with reduced sensitivity to Cd2+ block showed enhanced
      sensitivity after the application of sulfhydryl reducing agents. These results
      allow identification of residue pairs capable of approaching one another to
      within less than 3.5 A. We often observed that multiple consecutive adjacent
      residues in one P-loop could coordinately bind Cd2+ with a single residue in
      another P-loop. These results suggest that, on the time-scale of Cd2+ binding to
      mutant Na+ channels, P-loops show a high degree of flexibility.

PMID- 9234173
TI  - Multinational, multicultural, and multiprofessional lessons.

PMID- 9234170
TI  - Two metabotropic gamma-aminobutyric acid receptors differentially modulate
      calcium currents in retinal ganglion cells.
AB  - Metabotropic gamma-aminobutyric acid (GABA) receptors were studied in amphibian
      retinal ganglion cells using whole cell current and voltage clamp techniques. The
      aim was to identify the types of receptor present and their mechanisms of action
      and modulation. Previous results indicated that ganglion cells possess two
      ionotropic GABA receptors: GABAAR and GABACR. This study demonstrates that they
      also possess two types of metabotropic GABAB receptor: one sensitive to baclofen
      and another to cis-aminocrotonic acid (CACA). The effects of these selective
      agonists were blocked by GDP-beta-S. Baclofen suppressed an omega-conotoxin-GVIA
      sensitive barium current, and this action was reversed by prepulse facilitation,
      indicative of a direct G-protein pathway. The effect of baclofen was also
      partially occluded by agents that influence the protein kinase A (PKA) pathway.
      But the effect of PKA activation was unaffected by prepulse facilitation,
      indicating PKA acted through a parallel pathway. Calmodulin antagonists reduced
      the action of baclofen, whereas inhibitors of calmodulin phosphatase enhanced it.
      Antagonists of internal calcium release, such as heparin and ruthenium red; did
      not affect the baclofen response. Thus, the baclofen-sensitive receptor may
      respond to influx of calcium. The CACA-sensitive GABA receptor reduced current
      through dihydropyridine-sensitive channels. Sodium nitroprusside and 8-bromo-cGMP
      enhanced the action of CACA, indicating that a nitric oxide system can up
      regulate this receptor pathway. CACA-sensitive and baclofen-sensitive GABAB
      receptors reduced spike activity in ganglion cells. Overall, retinal ganglion
      cells possess four types of GABA receptor, two ionotropic and two metabotropic.
      Each has a unique electrogenic profile, providing a wide range of neural
      integration at the final stage of retinal information processing.

PMID- 9234172
TI  - Regulatory volume decrease of cardiac myocytes induced by beta-adrenergic
      activation of the Cl- channel in guinea pig.
AB  - A new method was developed to automatically measure the thickness of a single
      ventricular myocyte of guinea-pig heart. A fine marker was attached on the cell's
      upper surface and changes in its vertical position were measured by focusing it
      under the microscope. When the osmolarity of the bath solution was varied, the
      cell thickness reached a new steady level without any obvious regulatory volume
      change within the period of observation up to 15 min. The cell thickness was 7.8
      +/- 0.2 microns (n = 94) in the control Tyrode solution and was varied to 130.4
      +/- 3.1% (n = 10), 119.1 +/- 1.1% (n = 50), 87.2 +/- 1.9% (n = 9), and 75.6 +/-
      3.2% (n = 5) of control at 50, 70, 130, and 200% osmolarity, respectively. The
      application of a Cl- channel blocker, 500 microM anthracene-9-carboxylic acid
      (9AC) did not modify these osmotic volume changes. We discovered that the
      application of isoprenaline induced a regulatory volume decrease (RVD) in cells
      inflated by hypotonic solutions. This isoprenaline-induced RVD was inhibited by
      antagonizing beta-adrenergic stimulation with acetylcholine. The isoprenaline
      induced RVD was mimicked by the external application of 8-bromoadenosine 3':5'
      cyclic monophosphate. The RVD was inhibited by blocking the cAMP-dependent Cl-
      channel (ICl, rAMP) with 9AC but was insensitive to 4,4'-diisothiocyanostilbene
      2,2'-dissulphonate (DIDS). Taken together these data suggest an involvement of
      ICl, cAMP activation in the RVD. Whole cell voltage clamp experiments revealed
      activation of ICl, cAMP by isoprenaline under the comparable conditions. The
      cardiac cell volume may be regulated by the autonomic nervous activity.

PMID- 9234174
TI  - Standardization of the CFU-GM assay using hematopoietic growth factors.

PMID- 9234175
TI  - Proposed approach to regulation of cellular and tissue-based products. The Food
      and Drug Administration.

PMID- 9234176
TI  - Enumeration of CD34-positive stem cells: evaluation and comparison of three
      methods.
AB  - Accurate enumeration of CD34+ stem cells is important in assessing the need for
      continued mobilization and subsequent apheresis collections. We compared two new
      analysis systems, ProCOUNT (Becton Dickinson Immunocytometry Systems) and IMAGN
      2000 STELLer (Biometric Imaging, Inc.) with our current (3-Color) flow cytometry
      based method. The ProCOUNT system uses an absolute counting tube, which contains
      reference beads and a specific (multiple) gating strategy to determine an
      absolute count. The STELLer assay combines microvolume fluorimetry and automated
      analysis software to determine an absolute count. To evaluate linearity and
      reproducibility, peripheral blood was spiked with CD34+ cells (KG1a cell line).
      Three dilution series (measured at approximately equal to 0, 5, 10, 25, 50, and
      100 CD34+ cells/microliter) were analyzed by each method. Analysis of predicted
      versus actual CD34+ concentration showed excellent correlation with all methods
      (r2 > or = 0.97, slope 0.98-1.04). To further assess precision, two PBSC samples,
      at approximately 200 and 800 CD34+ cells/microliter, respectively, were analyzed
      10 times by each method. Coefficients of variation for the precision analysis of
      these samples were 5.1%-6.4% and 5.4%-12.3%, respectively. To assess overall
      performance, 75 patient specimens were analyzed. Excellent correlation (r2 values
      of 0.89-0.98) was observed among all three methods. We conclude that the three
      methods provide comparable linearity and reproducibility.

PMID- 9234177
TI  - Stem cell mobilization in normal donors.
AB  - We studied peripheral blood and apheresis samples from 39 consecutive normal
      donors who were parents or siblings of patients who received matched or
      mismatched bone marrow transplants using a combination of rhG-CSF-mobilized
      peripheral blood stem cells (PBSCs) and bone marrow (BM). BM was harvested from
      donors 1-7 days before starting rhG-CSF treatment: 12 micrograms/kg/day rhG-CSF
      was administered by continuous s.c. infusion for 4-7 days. Peripheral blood
      progenitor cells were harvested by leukapheresis using an automated continuous
      flow blood cell separator, beginning on day 4 of rhG/CSF, for 1-4 consecutive
      days. Peak peripheral blood CD34+ cell and CFU-GM levels were reached
      simultaneously on day 5 or 6 of rhG-CSF administration. Median peak levels were
      1.65% for CD34+ cells (range 0.34%-4.7%) and 142 CFU-GM/10(5) plated cells (range
      16-700). The greatest numbers of CD34+ cells and CFU-GM, expressed per liter of
      blood volume processed, were harvested during the second and third leukapheresis:
      CD34+ cells 37.77 +/- 25.48 x 10(6) and CFU-GM 3.32 +/- 2.51 x 10(6) during the
      second leukapheresis, and CD34+ cells 37.01 +/- 16.33 x 10(6) and CFU-GM 3.82 +/-
      4.36 x 10(6) during the third. The number of CD34+ cells and CFU-GM did not
      correlate with the sex, age, or body weight of the donors. This study indicates
      that this protocol for administration of rhG-CSF mobilizes large numbers of
      hematopoietic progenitor cells into the peripheral blood and that bone marrow
      harvesting before G-CSF administration does not impair stem cell mobilization.

PMID- 9234178
TI  - Positive selection and transplantation of peripheral CD34+ progenitor cells:
      feasibility and purging efficacy in pediatric patients with neuroblastoma.
AB  - Peripheral stem cells were mobilized and collected in 20 children with stage 4
      neuroblastoma. A total of 37 leukaphereses were performed in the 20 patients. The
      mean number of collected cells was 5.6 +/- 2.4 x 10(8)/kg (range 1.9-10.5), and
      the number of collected CD34+ progenitors was 6.1 +/- 6.3 x 10(6)/kg (range 0.75
      21.7). CD34-positive selection was performed using the CellPro method. Of the
      adsorbed cells, 42 +/- 20% (range 4.3-76.6) stained positively for CD34, and the
      number of positively selected CD34+ cells was 2.0 +/- 1.9 x 10(6)/kg (range 0.09
      7.1). The mean recovery of CD34+ cells was 36 +/- 20% (range 6-67). For detection
      of contaminating neuroblastoma cells before and after CD34-positive selection, a
      murine antidisialoganglioside GD2 antibody (14.G2a) was used, followed by the
      alkaline phosphatase antialkaline phosphatase (APAAP) method. Before the positive
      selection, various numbers of contaminating neuroblastoma cells were found in the
      leukaphereses of 7 patients. After positive selection, neuroblastoma cells were
      still detectable in all 7 patients, with a mean log depletion of tumor cells of
      1.41 +/- 0.45 (range 0.69-2.13). In 1 patient, contaminating neuroblastoma cells
      were found only after CD34-positive selection. In 15 of the 20 patients, high
      dose chemotherapy was performed, and positively selected CD34+ cells were
      reinfused in 12 patients. In 10 of these, the mean time to reach > 0.5 x 10(9)/L
      granulocytes was 12.3 +/- 1.7 days (range 10-16). One patient died at day 7 due
      to sepsis, and in 1 patient the backup was given at day 15. Because of the low
      number of collected CD34+ cells, 3 patients were grafted with a combination of
      unmanipulated PBSC and CD34+ progenitors. In summary, we have shown that positive
      selection of peripheral CD34+ progenitors is feasible in pediatric patients.
      However, strategies to improve the recovery of the CD34+ cells and the purging
      efficacy of this method (i.e., higher enrichment of CD34+ cells, combination of
      positive and negative selection methods) should be evaluated further.

PMID- 9234179
TI  - Lineage commitment of HLA-DR/CD38-defined progenitor cell subpopulations in bone
      marrow and mobilized peripheral blood assessed by four-color immunofluorescence.
AB  - We used four-color fluorescence analysis to compare lineage antigen expression in
      relationship to CD38 and HLA-DR on CD34+ progenitor cells in adult human bone
      marrow and mobilized peripheral blood. Each of four progenitor cell
      subpopulations defined by HLA-DR and CD38 intensity (CD38-/HLA-DR-, CD38-/HLA
      DR+, CD38+/HLA-DR+, and CD38+/HLA-DR-) were present in both progenitor cell
      sources in similar ratios. The most prevalent subpopulation consisted of cells
      that expressed both CD38 and HLA-DR. Virtually all progenitor cells that lacked
      CD38 also lacked lineage antigens regardless of their HLA-DR expression. In
      contrast, the majority of the cells within both CD38+ progenitor cell
      subpopulations possessed either lineage antigens or the proliferation-associated
      antigen, CD71. Furthermore, CD71 was expressed on three times the number of
      CD38+/HLA-DR- cells when compared with the CD38-/HLA-DR- subpopulation. Within
      CD34+ progenitor cell subpopulations defined by the expression of CD38 and HLA
      DR, the CD38+/HLA-DR- component appears to be the most mature, based on the
      expression of CD71 and various lineage-associated antigens, including
      representative markers characterizing early lymphoid, myeloid, and erythroid
      precursors. Thus, selection of the most immature CD34+ progenitor cells based
      solely on the lack of HLA-DR expression results in isolation of two distinct cell
      populations with markedly different maturation status and resultant growth
      characteristics.

PMID- 9234180
TI  - Efficient harvest of in vivo IL-2-activated CD3+ lymphocytes for adoptive
      immunotherapy by selective leukapheresis (lymphocytapheresis).
AB  - Autologous activated lymphocytes are an alternative to tumor-infiltrating
      lymphocytes for adoptive immunotherapy. We developed a method of selective
      lymphocytapheresis that harvests large numbers of interleukin-2 (IL-2)-activated
      autologous T lymphocytes. Five patients with metastatic malignant melanoma
      received 2.4 x 10(6) IU/m2 IL-2 sc. once a day 5 days a week for 3 weeks before
      lymphocytapheresis. Four patients went through lymphocytapheresis without IL-2
      pretreatment. After IL-2 pretreatment, activated memory T cells increased
      significantly. Increasing CD3+ cells paralleled the significant enhancement of
      the cytotoxic activity against an HLA-A2-matched allogeneic melanoma cell line
      during the 3 weeks of IL-2 pretreatment. Lymphocytapheresis was performed 72 h
      after the last IL-2 injection to obtain the maximum recovery of activated
      lymphocytes at the peak of the rebound phenomenon. IL-2 pretreatment resulted in
      many more lymphocytes in the harvest than without pretreatment. The percentage,
      number, and lytic units of CD3+ cells harvested by the differential apheresis
      were significantly higher than were present in peripheral blood before
      lymphocytapheresis. These results show that pretreatment of melanoma patients
      with low-dose IL-2 before lymphocytapheresis allows the selective harvest of
      large numbers of activated T lymphocytes for adoptive immunotherapy.

PMID- 9234181
TI  - Immunomagnetic bone marrow purging in children with acute lymphoblastic leukemia.
AB  - Autologous bone marrow transplantation (ABMT) offers a therapeutic alternative
      for children with poor prognosis acute lymphoblastic leukemia (ALL) who lack an
      HLA-matched sibling donor. The most common cause of treatment failure after ABMT
      in these patients is leukemia relapse. We have developed an ex vivo autologous
      marrow purging program for children with ALL using an immunomagnetic method. BM
      purging has been performed in 37 children with ALL (31 B-lineage ALL and 6 T
      lineage ALL) following an indirect method, using panels of mouse monoclonal
      antibodies (MAbs) directed against B or T cell antigens, Dynabeads M-450 (Dynal)
      coated with sheep antimouse (SAM) antibodies, and the MaxSep Magnetic Cell
      Separator (Baxter). Purging efficiency has been assessed by flow cytometry.
      Considering the limit of detection of target cells 0.1%, the median depletion was
      2.0 log (range 0.8- > 2.8 log) for the B-lineage ALL and 2.7 (range 2.2- > 2, 9
      log) for the T-lineage ALL patients. Twenty-seven patients have been autografted
      (6 in first complete remission, CR, 13 in second CR, and 8 in third or subsequent
      CR). Engraftment has been satisfactory in all of them, reaching levels of 500
      neutrophils/mm3 and 20,000 platelets/mm3 after a median of 17 (range 12-39) and
      30 (range 13-96) days post-ABMT, respectively. In summary, our results show that
      this immunomagnetic procedure achieves high levels of target cell depletion and
      can be safely applied to bone marrow purging in childhood ALL patients.

PMID- 9234182
TI  - Red cell depletion of umbilical cord blood (UCB): comparison between
      unmanipulated and red cell-depleted UCB by Ficoll-Paque density gradient
      separation.
AB  - Stem cells from umbilical cord blood (UCB) represent an alternative source of
      cells for clinical transplantation. Many issues remain unsolved with regard to
      their collection, manipulation, and storage. In this study, we attempted to
      compare the effect of red cell depletion by Ficoll-Paque density gradient
      separation versus unmanipulated cord blood stem cells postthawing. We found no
      statistical difference between the two technologies when comparing viability,
      98.6 +/- 0.3% versus 99.1 +/- 0.42% (p = < 0.16); CD34+/CD38+, 1.6 +/- 0.13%
      versus 1.2 +/- 0.17% (p = < 0.13); HLA DR+/CD34+, 1.8 +/- 0.15% versus 1.9 +/-
      0.21% (p = < 0.6); blast colonies, 8.0 +/- 1.5 versus 12.2 +/- 2.1 (p = < 0.15);
      CFU-GEMM colonies, 143.7 +/- 27.9 versus 80.7 (p = < 0.10); CFU-GM colonies,
      101.2 +/- 23 versus 173 +/- 23.2 (p = < 0.07). There was a statistical difference
      in the content of CD34+/CD38+, 1.6 +/- 0.14% versus 1.2 +/- 0.14% (p = < 0.05),
      and the BFU-E colonies, 96 +/- 29.8 versus 165 +/- 23.9 (p = < 0.03). We conclude
      that red cell depletion using Ficoll-Paque gradient separation preserves
      viability of progenitor cells, as evidenced by immunophenotyping and colony
      assays.

PMID- 9234183
TI  - Burning mouth syndrome (BMS) and the concept of alexithymia--a preliminary study.
AB  - Twenty women suffering from burning mouth syndrome (BMS) were rated with regard
      to alexithymic traits, depressive symptoms and anxiety; values were compared to
      disability level assessed by interviews. Results confirm earlier reports that BMS
      symptomatology is associated with depression and anxiety. The majority of
      patients were rated as alexithymic and, supported by interview data; these
      results indicate that somatization should be taken into consideration during
      clinical evaluation of BMS symptoms. The study included a psychological analysis
      of the communication pattern in the patient-doctor relationship, leading to the
      assumption that the patient's appeal for somatic treatment, dependency and
      hopelessness may activate defensive reactions in the dentist. Such reactions can
      be either rejection of, or compliance with, the patient's demands. The importance
      of a differentiated assessment and treatment approach for these patients is
      emphasized. Due to lack of control data the report should be viewed as a pilot
      study.

PMID- 9234184
TI  - Immunocytochemical detection of autoantibody deposits in Tzanck smears from
      patients with oral pemphigus.
AB  - Eighteen patients, ten affected by pemphigus vulgaris and four affected by herpes
      simplex of the oral mucosa, together with four healthy patients as controls, were
      investigated by cytologic examination of Papanicolaou stained smears obtained by
      scraping the oral mucosa. In all cases additional smears were immunostained with
      the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using
      monoclonal antibodies against human heavy IgG chains and lambda light chains. The
      results have shown that, for a cytological diagnosis of pemphigus, this technique
      can be used as an easy substitute for the immunofluorescence test and does not
      require any specialized training or equipment. The findings are clearly
      detectable by light microscopy and allow, together with the immunostaining, an
      adequate visualization of cell morphology.

PMID- 9234185
TI  - An immunohistochemical study of thrombomodulin in oral squamous cell carcinoma
      and its association with invasive and metastatic potential.
AB  - Thrombomodulin (TM) is a glycoprotein that was originally identified on vascular
      endothelium and characterized as a natural endothelial anticoagulant. We reported
      previously that TM was also expressed at cell-cell boundaries of squamous
      epithelium, except in the basal layer cells and upper granular layer cells. The
      expression pattern of TM in the squamous cells implies that this molecule might
      be associated with keratinocyte differentiation, as well as being a potent
      anticoagulant. In the present study we examined TM expression
      immunohistochemically in biopsy specimens from 65 patients with primary oral
      squamous cell carcinoma (OSCC), and compared the results with the biological
      behavior of the carcinomas. The patients with intense TM expression in the
      carcinoma showed a significantly lower frequency of lymph node metastasis and
      significantly more favorable survival than those with negative TM expression. The
      TM expression was a better marker than the other prognostic factors, such as
      differentiation degree, tumor size and invasion mode. When TM expression was
      compared between the primary and metastatic lesions in the 36 patients who had
      lymph node metastasis, 14 (39%) showed decreased TM expression, 19 (53%) showed
      no change, and 3 (8%) showed an increase in the metastatic lesions. Wilcoxon's
      signed-rank test indicated that tumor cells positive for TM expression were
      significantly rarer in the metastatic lesions than in the primary tumors (P <
      0.05). These results indicate that reduced expression of TM is associated with
      metastasis of carcinoma cells. The reduction of TM expression seems to play an
      important role in the metastatic process of OSCC, and to be related with a poor
      outcome for the patients.

PMID- 9234186
TI  - Features of odontogenesis and expression of cytokeratins and tenascin-C in three
      cases of extraosseous and intraosseous calcifying odontogenic cyst.
AB  - To characterize further the nature of calcifying odontogenic cyst (COC), we
      studied histologically and immunohistochemically an extraosseous and two
      intraosseous lesions. The extraosseous COC was in continuity with the stratified
      squamous epithelium of the alveolar mucosa. Immunostaining with monoclonal
      antibodies showed reactivity of both low- and high-molecular-weight cytokeratins,
      the degree of coexpression decreasing with the increasing morphological diversity
      of the cyst/tumour epithelium. Staining for the matrix glycoprotein tenascin-C
      was seen not only in the connective tissue, where its distribution patterns
      corresponded to the stage of hard tissue formation, but also in epithelial
      elements. The staining patterns were analogous to those described during normal
      tooth formation. Both the morphological characteristics and expression patterns
      of the various cytokeratin types and tenascin-C implied that COC represents a
      pathological counterpart of normal odontogenesis. In the case of the extraosseous
      COC, the correspondence could be traced back to early stages of tooth
      development.

PMID- 9234187
TI  - Immunohistochemical demonstration of bone morphogenetic protein in odontogenic
      tumors.
AB  - The aim of the present study was to describe the expression and distribution of
      bone morphogenetic protein (BMP) in odontogenic tumors by immunohistochemistry
      using monoclonal antibody against bovine BMP (BMPMcAb). Eight types of
      odontogenic tumors (44 cases), including ameloblastoma (20 cases), cementifying
      fibroma (8 cases), benign cementoblastoma (5 cases), dentinoma (3 cases),
      compound odontoma (2 cases), adenomatoid odontogenic tumor (2 cases), calcifying
      epithelial odontogenic tumor (2 cases) and odontogenic fibroma (2 cases), were
      studied. The results showed that, according to the immunostaining pattern of
      BMPMcAb, tumors could be classified into two types: all cementifying fibromas,
      benign cementoblastomas, dentinomas, odontogenic fibromas, and compound odontomas
      demonstrated a positive reaction, whereas all ameloblastomas, adenomatoid
      odontogenic tumors, and calcifying epithelial odontogenic tumors were negative.
      BMPMcAb-positive odontogenic tumors were those tumors with formation of enamel,
      dentin, cementum or bone. Therefore, BMP might play an important role in the
      formation of calcified dental tissues and the development of odontogenic tumors
      contaning such tissues.

PMID- 9234188
TI  - The articular disc surface in different functional conditions of the human
      temporo-mandibular joint.
AB  - The peripheral discal tissue and the surface covering layer have been studied in
      normal and in variously damaged human temporo-mandibular joint discs. In the
      normal disc the tissue consisted of dense bundles of fibers and rare fibrocytes.
      The surface of the disc was covered by a regular basophilic and electron-dense
      layer. These morphological characteristics persisted also in some pathological
      discs in which fibrous derangements had already occurred in the deep parts. In
      very deformed and damaged discs associated with serious functional anomalies, the
      superficial discal tissue consisted of rare fibers dispersed in a loose ground
      substance and of an increased number of cells. The superficial coating was formed
      by an irregular dense lamina and aggregates of various materials containing
      cellular debris, vesicles, filaments and amorphous components. These deposits are
      probably due to degeneration processes of discal tissue. This investigation
      suggests that the superficial discal tissue and the covering layer are together
      involved in maintaining the functional properties of the articular surfaces.
      Their structural modification in severe functional anomalies leads to failure in
      the maintenance of nonadherence conditions and to deterioration of the functional
      defect.

PMID- 9234189
TI  - Comparison between submucosal (extra-nodal) and nodal non-Hodgkin's lymphoma
      (NHL) in the oral and maxillofacial region.
AB  - Fifty-two cases of non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial
      region, comprising 31 submucosal (extra-nodal) and 21 cervical node NHLs, were
      investigated. The patients' ages ranged from 5 to 86 years, with a bimodal age
      distribution among young people below 12 years of age (average 8 years) and in
      those aged 30 years or older (average 60.3 years). The male-to-female gender
      difference ratio was 1.3:1. Patients presented with swelling as the major
      symptom. Histologically, diffuse, large cell malignant lymphoma was the most
      frequent type and 67.9% of lymphomas were of intermediate malignancy as defined
      by the Working Formulation for Clinical Usage. All submucosal lymphomas showed
      diffuse proliferation patterns, although follicular proliferation was identified
      in 5 of the 21 nodal lymphomas. Immunohistochemistry showed that the B-cell type
      was predominant, especially in nodal lymphomas.

PMID- 9234190
TI  - Exfoliative cheilitis (EC) in AIDS: association with Candida infection.
AB  - Forty-seven of 165 patients with AIDS (28.5%) showed exfoliative cheilitis (EC),
      predominantly of the lower lip (n = 37). Histologically, hyphae were revealed in
      23 of 47 cases (49%). In 14 of 23 specimens the histological and microbiological
      findings were in accordance. Smears of the vermilion border revealed Candida
      albicans in half of the cases (51%); however, combinations with C. krusei, C.
      tropicalis and C. glabrata were also seen. Twenty of 35 patients given
      fluconazole either prophylactically or therapeutically showed clinical signs of
      oral candidiasis. Frequent moistening of the lips may result in infection of the
      vermilion border with Candida species; consequent desiccation of the lips will
      lead to scale formation and exfoliation. Smears of the vermilion border of the
      lower lip of 20 controls with AIDS were positive in four cases. Twenty HIV
      negative controls without EC showed negative microbiological results for Candida
      species. Exfoliative cheilitis may be associated with Candida infection in some
      cases and may be considered another variant of candidiasis in AIDS patients.

PMID- 9234191
TI  - Localised oral histoplasmosis lesions associated with HIV infection.
AB  - Opportunistic fungal infections account for a significant amount of morbidity
      associated with HIV disease. We report here a case of localised oral
      histoplasmosis without evidence of disseminated disease in a patient who lacked
      stigmata of HIV disease at the time of initial presentation. The diagnosis is
      based on histology with special stains, complement fixing antibodies in serum,
      and culture of the organism from fresh tissues. Activation of subclinical disease
      following an infection in Uganda may explain the development of these exophytic
      oral lesions in this British resident.

PMID- 9234192
TI  - To quark or to spark, that is the question.

PMID- 9234193
TI  - Small event Ca2+ release: a probable precursor of Ca2+ sparks in frog skeletal
      muscle.
AB  - 1. Fluo-3 fluorescence associated with Ca2+ release was recorded with confocal
      microscopy in single muscle fibres. Clamp depolarization to -65 or -60 mV
      elicited Ca2+ sparks with amplitudes and spatial widths distributed approximately
      normally, with mean values of 0.79 of resting fluorescence and 0.8 micron (S.D.,
      0.17 and 0.2 micron; n = 193), respectively. Given these distributions, events of
      amplitude less than 0.45 or width less than 0.4 micron are unlikely to be sparks.
      2. Low voltage depolarization (-72 mV) elicited only one spark per triad every 6
      s, but generated a relative increase in fluorescence at triads of 0.05. This
      increase must therefore have been due to events smaller than sparks. 3. The
      variance/mean ratio of triadic fluorescence gradients averaged 0.11 at low
      voltages and increased severalfold at the higher voltages at which sparks
      appeared, indicating the existence of at least two event amplitudes. 4.
      Tetracaine (200 microM) reversibly abolished sparks and the early peak of Ca2+
      release at all voltages. In its presence, discrete events were smaller than the
      spark criterion, and triadic gradients had a variance/mean ratio of 0.11. 5. The
      phenylalkylamine D600 (2 microM) reduced release at all voltages, abolishing
      sparks and the peak of Ca2+ release at low but not at high voltages. 6. The
      parallel abolition of all sparks and the peak of Ca2+ release indicates that both
      phenomena are activated by Ca2+. The restoration of sparks by voltage in D600
      suggests that release in small events provides the trigger Ca2+ for activation of
      sparks.

PMID- 9234194
TI  - Release and sequestration of calcium by ryanodine-sensitive stores in rat
      hippocampal neurones.
AB  - 1. The properties of ryanodine-sensitive Ca2+ stores in CA1 pyramidal cells were
      investigated in rat hippocampal slices by using whole-cell patch-clamp recordings
      combined with fura-2-based fluorometric digital imaging of cytoplasmic Ca2+
      concentration ([Ca2+]i). 2. Brief pressure applications of caffeine onto the
      somata of pyramidal cells caused large transient increases in [Ca2+]i (Ca2+
      transients) of 50-600 nM above baseline. 3. The Ca2+ transients evoked by
      caffeine at -60 mV were not associated with an inward current, persisted after
      blocking voltage-activated Ca2+ currents and were completely blocked by bath
      applied ryanodine. Similar transients were also evoked at +60 mV. Thus, these
      transients reflect Ca2+ release from intracellular ryanodine-sensitive Ca2+
      stores. 4. The Ca2+ transients evoked by closely spaced caffeine pulses rapidly
      decreased in amplitude, indicating progressive depletion of the Ca2+ stores. The
      amplitude of the Ca2+ transients recovered spontaneously with an exponential time
      constant of 59 s. Recovery was accelerated by depolarization-induced elevations
      in [Ca2+]i and blocked by cyclopiazonic acid (CPA) and thapsigargin, indicating
      that store refilling is mediated by endoplasmic reticulum Ca(2+)-ATPases. 5. Even
      without prior store depletion the caffeine-induced Ca2+ transients disappeared
      after 6 min exposure to CPA, suggesting that ryanodine-sensitive Ca2+ stores are
      maintained at rest by continuous Ca2+ sequestration. 6. Caffeine-depleted Ca2+
      stores did not refill in Ca(2+)-free saline, suggesting that the refilling of the
      stores depends upon Ca2+ influx through a 'capacitative-like' transmembrane
      influx pathway operating at resting membrane potential. The refilling of the
      stores was also blocked by Ni2+ and gallopamil (D600). 7. Elevations of basal
      [Ca2+]i produced by bath-applied KCl markedly potentiated (up to 6-fold) the
      caffeine-induced Ca2+ transients. The degree of potentiation was positively
      related to the increase in basal [Ca2+]i. The Ca2+ transients remained
      potentiated up to 9 min after reversing the KCl-induced [Ca2+]i increase. Thus,
      the ryanodine-sensitive Ca2+ stores can 'overcharge' when challenged with an
      increase in [Ca2+]i and slowly discharge excess Ca2+ after basal [Ca2+]i returns
      to its resting level. 8. Pressure applications of caffeine onto pyramidal cell
      dendrites evoked local Ca2+ transients similar to those separately evoked in the
      respective somata. Thus, dendritic ryanodine-sensitive Ca2+ stores are also
      loaded at rest and can function as independent compartments. 9. In conclusion,
      the ryanodine-sensitive Ca2+ stores in hippocampal pyramidal neurones contain a
      releasable pool of Ca2+ that is maintained by a Ca2+ entry pathway active at
      subthreshold membrane potentials. Ca2+ entry through voltage-gated Ca2+ channels
      transiently overcharges the stores. Thus, by acting as powerful buffers at rest
      and as regulated sources during activity, Ca2+ stores may control the waveform of
      physiological Ca2+ signals in CA1 hippocampal pyramidal neurones.

PMID- 9234195
TI  - Mechanism of extracellular Ca2+ receptor-stimulated hormone release from sheep
      thyroid parafollicular cells.
AB  - 1. Expression of receptors to extracellular calcium enables parafollicular cells
      of the thyroid gland (PF cells) to release calcitonin (CT) and serotonin (5-HT)
      in response to increased external Ca2+. Recently, a calcium-sensing receptor
      (CaR), similar to the G protein-coupled receptor for external Ca2+ cloned from
      parathyroid gland, was shown to be expressed in PF cells. Using a highly purified
      preparation of sheep PF cells, we have examined the electrical and biochemical
      processes coupling CaR activation to hormone release. 2. Whole-cell recordings in
      the permeabilized-patch configuration show that elevated extracellular Ca2+
      concentration ([Ca2+]0) depolarizes these cells and induces oscillations in
      membrane potential. In voltage clamp, high [Ca2+]0 activates a cation conductance
      that underlies the depolarization. This conductance is cation selective, with a
      reversal potential near -25 mV indicating poor ion selectivity. 3. The CaR
      expressed in these cells is activated by other multivalent cations with a rank
      order potency of Gd3+ > Ba2+ > Ca2+ > > Mg2+. The insensitivity of these cells to
      high external Mg2+ contrasts with the reported sensitivity of the cloned CaR from
      parathyroid. 4. Elevation of [Ca2+]0 also stimulates increases in intracellular
      Ca2+ concentration ([Ca2+]i) and this effect is largely inhibited by the Ca2+
      channel blocker nimodipine, indicating that L-type voltage-gated Ca2+ channels
      contribute to the response to elevated [Ca2+]0. 5. Elevated [Ca2+]0 induces an
      inward current under conditions where the only permeant external cation is Ca2+,
      indicating that influx via the cation conductance is another source of the
      increases in [Ca2+]i. 6. Extracellular Ca2+ stimulates 5-HT release with an EC50
      of 1.5 mM. Nimodipine blocks 90% of the Ca2+0-induced 5-HT release, while other
      inhibitors of voltage-gated calcium channels had no effect. These data support an
      important role for L-type Ca2+ channels in CaR-induced hormone secretion.
      Although earlier studies indicate that high [Ca2+]0 induces release of Ca2+ from
      intracellular stores, thapsigargin-induced depletion of these stores did not
      affect secretion from these cells, indicating that Ca2+ influx is necessary and
      sufficient for the Ca2+0-induced 5-HT secretion. 7. Inhibition of protein kinase
      C (PKC) using chelerythrine, staurosporine, or calphostin C inhibited Ca2+0
      induced 5-HT release by 50% while phorobol ester-induced 5-HT secretion was
      completely inhibited. Thus, PKC is an important component of the pathway linking
      CaR activation to hormone release. However, another as yet unknown second
      messenger also contributes to this pathway. 8. We tested the contribution of two
      different phospholipases to the CaR responses to determine the source of the PKC
      activator diacylglycerol (DAG). Selective inhibition of phosphatidylinositol
      specific phospholipase C (PI-PLC) with U73122 had no effect on the response to
      elevated [Ca2+]0. However, pretreatment with D609, a selective inhibitor of
      phosphatidylcholine-specific phospholipase C (PC-PLC), inhibited Ca(2+)-induced 5
      HT release to 50% of control indicating that phosphatidylcholine is a likely
      source of DAG in the response of PF cells to elevated [Ca2+]0.

PMID- 9234196
TI  - A quantitative analysis of the activation and inactivation kinetics of HERG
      expressed in Xenopus oocytes.
AB  - 1. The human ether a-go-go-related gene (HERG) encodes a K+ channel that is
      believed to be the basis of the delayed rectified current, IKr, in cardiac
      muscle. We studied HERG expressed in Xenopus oocytes using a two-electrode and
      cut-open oocyte clamp technique with [K+]0 of 2 and 98 mM. 2. The time course of
      activation of the channel was measured using an envelope of tails protocol and
      demonstrated that activation of the heterologously expressed HERG current (IHERG)
      was sigmoidal in onset. At least three closed states were required to reproduce
      the sigmoid time course. 3. The voltage dependence of the activation process and
      its saturation at positive voltages suggested the existence of at least one
      relatively voltage-insensitive step. A three closed state activation model with a
      single voltage-insensitive intermediate closed state was able to reproduce the
      time and voltage dependence of activation, deactivation and steady-state
      activation. Activation was insensitive to changes in [K+]0. 4. Both inactivation
      and recovery time constants increased with a change of [K+]0 from 2 to 98 mM.
      Steady-state inactivation shifted by approximately 30 mV in the depolarized
      direction with a change from 2 to 98 mM K+0. 5. Simulations showed that
      modulation of inactivation is a minimal component of the increase of this current
      by [K+]0, and that a large increase in total conductance must also occur.

PMID- 9234197
TI  - Outward potassium currents of supraoptic magnocellular neurosecretory cells
      isolated from the adult guinea-pig.
AB  - 1. Several types of whole-cell outward K+ current recorded from magnocellular
      neurosecretory cells (MNCs) dissociated from the supraoptic nucleus of the adult
      guinea-pig were identified on the basis of their voltage dependence, kinetics,
      pharmacology and Ca2+ dependence. 2. The predominant K+ current evoked from a
      holding potential of -40 mV was slowly activating, long-lasting,
      tetraethylammonium (TEA) sensitive and showed little steady-state inactivation.
      Also, this current was reduced by extracellular Cd2+. These data suggest that in
      supraoptic MNCs classical Ca(2+)-insensitive, delayed rectifier channels (KV) and
      Ca(2+)-sensitive, non-inactivating channels (KCa) both contribute to the
      sustained current. 3. A transient, low-threshold K+ current, which was 4
      aminopyridine (4-AP) sensitive and showed significant steady-state inactivation,
      was evoked along with the sustained current from a holding potential of -90 mV.
      Based on these characteristics, this current corresponds to the A-current (IK(A))
      described in other neurons. 4. IK(A) was activated when Ca2+ influx was blocked
      or when Ca2+ was absent from the extracellular medium, suggesting that Ca2+
      influx is not necessary for activation of the current. 5. In many recordings, a
      transient 4-AP-insensitive outward current was evoked from a holding potential of
      -40 mV. This high-threshold transient K+ current was abolished by extracellular
      Cd2+ or TEA and was absent when extracellular Ca2+ was replaced by Sr2+,
      suggesting that it is a transient Ca(2+)-dependent K+ current. 6. We conclude
      that the presence of multiple types of K+ current may, in part, underlie the
      complex firing patterns of oxytocinergic and vasopressinergic MNCs.

PMID- 9234198
TI  - Regulation of muscarinic acetylcholine receptor-mediated synaptic responses by
      adenosine receptors in the rat hippocampus.
AB  - 1. Intracellular current clamp recordings were made from CA1 pyramidal neurones
      in rat hippocampal slices. Experiments were performed in the presence of
      ionotropic glutamate receptor antagonists and gamma-aminobutyric acid (GABA)
      receptor antagonists to block all fast excitatory and inhibitory synaptic
      transmission. A single stimulus, delivered extracellularly in the stratum oriens,
      caused a reduction in spike frequency adaptation in response to a depolarizing
      current step delivered 2 s after the stimulus. A 2- to 10-fold increase in
      stimulus intensity evoked a slow excitatory postsynaptic potential (EPSP) which
      was associated with a small increase in input resistance. The peak amplitude of
      the EPSP occurred approximately 2.5 s after the stimulus and its magnitude (up to
      30 mV) and duration (10-50 s) increased with increasing stimulus intensity. 2.
      The slow EPSP was unaffected by the metabotropic glutamate receptor antagonist
      (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG; 1000 microM) but was greatly
      enhanced by the acetylcholinesterase inhibitor physostigmine (1-5 microM). Both
      the slow EPSP and the stimulus-evoked reduction in spike frequency adaptation
      were inhibited by the muscarinic acetylcholine receptor (mAChR) antagonist
      atropine (1-5 microM). These results are consistent with these effects being
      mediated by mAChRs. 3. Both the mAChR-mediated EPSP (EPSPm) and the associated
      reduction in spike frequency adaptation were reversibly depressed (up to 97%) by
      either adenosine (100 microM) or its non-hydrolysable analogue 2-chloroadenosine
      (CADO; 0.1-5.0 microM). These effects were often accompanied by postsynaptic
      hyperpolarization (up to 8 mV) and a reduction in input resistance (up to 11%).
      The selective adenosine A1 receptor agonists 2-chloro-N6-cyclopentyladenosine
      (CCPA; 0.1-0.4 microM) and R(-)N6-(2-phenylisopropyl)-adenosine (R-PIA; 1 microM)
      both depressed the EPSPm. In contrast, the adenosine A2A receptor agonist 2-p-(2
      carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 0.5-1.0
      microM) did not significantly affect the EPSPm. 4. The selective adenosine A1
      receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.2 microM) fully
      reversed the depressant effects of both adenosine (100 microM) and CADO (1
      microM) on the EPSPm and the stimulus-evoked reductions in spike frequency
      adaptation. 5. DPCPX (0.2 microM) alone caused a small but variable mean increase
      in the EPSPm of 22 +/- 19% and enabled activation of an EPSPm by a previously
      subthreshold stimulus. In contrast, the selective adenosine kinase inhibitor 5
      iodotubercidin (5-IT; 10 microM) inhibited the EPSPm by 74 +/- 10%, an effect
      that was reversed by DPCPX. 6. The concentration-response relationship for the
      depressant action of CADO on the EPSPm more closely paralleled that for its
      presynaptic depressant action on glutamate-mediated EPSPs than that for
      postsynaptic hyperpolarization. The respective mean IC50 and EC50 concentrations
      for these effects were 0.3, 0.8 and 3.0 microM. 7. CADO (1-5 microM) did not have
      a significant effect on the postsynaptic depolarization, increase in input
      resistance and reduction in spike frequency adaptation evoked by carbachol (0.5
      3.0 microM). All these effects were abolished by atropine (1 microM). 8. These
      data provide good evidence for an adenosine A1 receptor-mediated inhibition of
      mAChR-mediated synaptic responses in hippocampal CA1 pyramidal neurones. This
      inhibition is mediated predominantly presynaptically, is active tonically and can
      be enhanced when extracellular levels of endogenous adenosine are raised.

PMID- 9234199
TI  - GABAA receptor-mediated IPSCs in rat thalamic sensory nuclei: patterns of
      discharge and tonic modulation by GABAB autoreceptors.
AB  - 1. The patterns of discharge of spontaneous GABAA-mediated inhibitory
      postsynaptic currents (sIPSCs), originating from the nucleus reticularis thalami
      (NRT), and their modulation by GABAB autoreceptors, were studied in rat
      thalamocortical (TC) neurones using whole-cell voltage-clamp recordings in brain
      slices. 2. sIPSCs were recorded in all ventro-basal (VB) and dorsal lateral
      geniculate (LGN) neurones. In VB neurones, in the presence of tetraethylammonium
      (TEA, 5 mM), these sIPSCs can occur in bursts at frequencies of either 0.1 or 1-2
      Hz. In the presence of tetrodotoxin (TTX), these bursting activities are replaced
      by the continuous discharge of miniature IPSCs (mIPSCs), recorded in the absence
      of TEA, at a frequency of 4 Hz. The kinetic properties of mIPSCs were similar in
      VB and LGN TC neurones. 3. In VB TC neurones the GABAB receptor agonist (+/-)
      baclofen, at a concentration of 0.05 microM, decreased the mIPSC frequency by 22%
      without affecting their amplitude distribution. Increasing the (+/-)-baclofen
      concentration to 1 and 10 microM caused similar reductions (41 and 47%,
      respectively) in the mIPSCs frequency: these values were significantly different
      from the one observed with 0.05 microM (+/-)-baclofen. In LGN TC neurones, where
      mIPSCs originate from both NRT and local interneurone terminals, 1 microM (+/-)
      baclofen produced a 66% reduction in the mIPSC frequency. 4. The GABAB receptor
      antagonist CGP55845A (50 nM) not only blocked the baclofen-mediated decrease in
      mIPSC frequency, but also produced a 52% increase in the mIPSC frequency compared
      with control in three out of seven neurones. Application of CGP55845A (50-500 nM)
      alone produced a 77% increase in the mIPSC frequency in three out of nine VB
      neurones, and in the LGN, CGP55845A (100 nM) produced a 53% increase in four out
      of nine neurones. CGP55845A (100 nM) also reversibly increased the amplitude of
      evoked GABAA IPSCs by 74 and 57% in three out of three VB and three out of five
      LGN neurones, respectively. 5. Application of GABA (1.5-5 microM) decreased the
      mIPSC frequency in VB TC neurones by a similar extent (48%) as 1-10 microM (+/-)
      baclofen. 6. In the presence of 100 microM Cd2+, (+/-)-baclofen still decreased
      the mIPSC frequency by about 40%, indicating that the effect of presynaptic GABAB
      receptor activation on spontaneous GABA release did not occur through a reduction
      of voltage-dependent Ca2+ currents. 7. Cd2+ (100 microM) decreased the amplitude
      of both mIPSCs and isoguvacine-induced current by 30 and 19%, respectively,
      indicating an effect of this divalent cation on postsynaptic GABAA receptors. 8.
      We conclude that GABAB autoreceptors are present on the GABAergic terminals
      within the thalamic sensory nuclei and that these receptors can be tonically
      activated by the ambient GABA.

PMID- 9234200
TI  - Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in
      mouse pancreatic B-cells.
AB  - 1. The mechanisms by which cAMP stimulates Ca(2+)-dependent insulin secretion
      were investigated by combining measurements of whole-cell Ca2+ currents, the
      cytoplasmic free Ca2+ concentration ([Ca2+]i) and membrane capacitance in single
      mouse B-cells maintained in tissue culture. 2. Cyclic AMP stimulated exocytosis >
      4-fold in whole-cell experiments in which secretion was evoked by intracellular
      dialysis with a Ca(2+)-EGTA buffer with a [Ca2+]i of 1.5 microM. This effect was
      antagonized by inhibitors of protein kinase A (PKA). 3. Photorelease of cAMP from
      a caged precursor potentiated exocytosis at Ca2+ concentrations which were
      themselves stimulatory (> or = 60 nM), but was without effect in the complete
      absence of Ca2+. 4. Elevation of intracellular cAMP (by exposure to forskolin)
      evoked a 6-fold PKA-dependent enhancement of the maximal exocytotic response
      (determined as the maximum increase in cell capacitance that could be elicited by
      a train of depolarizations) in perforated-patch whole-cell recordings. 5.
      Exocytosis triggered by single depolarizations in standard whole-cell recordings
      was strongly potentiated by cAMP, but in this case the effect was unaffected by
      PKA inhibition. 6. When exocytosis was triggered by Ca2+ released from Ca(2+)-NP
      EGTA ('caged Ca2+'), cAMP exerted a dual stimulatory effect on secretion: a rapid
      (initiated within 80 ms) PKA-independent phase and a late PKA-dependent
      component. 7. We conclude that cAMP stimulates insulin secretion both by
      increasing the release probability of secretory granules already in the readily
      releasable pool and by accelerating the refilling of this pool.

PMID- 9234201
TI  - Pressor effect mediated by bradykinin in the paratrigeminal nucleus of the rat.
AB  - 1. The participation of the paratrigeminal nucleus (Pa5) in the pressor response
      produced by bradykinin in the dorsolateral medulla of rats was investigated. The
      microinjection of 6 pmol of bradykinin directly over the paratrigeminal nucleus
      of unanaesthetized rats produced a significant increase in arterial pressure and
      a moderate increase in heart rate. 2. Bradykinin microinjections in different
      sites surrounding the Pa5 compromising the external cuneate nucleus, the
      trigeminal nucleus, the lateral and ventral spinal trigeminal tract and the
      dorsal trigeminal tract rostral and caudal to the Pa5 did not elicit significant
      pressor responses. In contrast, microinjections in the paratrigeminal nucleus
      produced pressor effects. Injections in the dorsolateral medulla directly over
      the paratrigeminal nucleus produced larger responses than when injections were
      made in the nucleus. Saline injections in the different nuclei did not produce
      pressor effects. 3. Neurochemical lesioning of the Pa5, with microinjections of
      ibotenic acid in the Pa5, abolished the pressor response to bradykinin injected
      over the lesioned nucleus. The effect was present, however, when bradykinin was
      injected on the contralateral side to the lesion, over the intact nucleus of the
      same animal. Pretreatment with capsaicin (injected in the lateral cerebral
      ventricle), which causes selective degeneration of afferent sensory fibres, did
      not alter the pressor effect of bradykinin injected over the paratrigeminal
      nucleus. 4. Dose-related responses were produced by different concentrations of
      bradykinin (0.6-1.8 pmol) microinjected over the nucleus. The bradykinin receptor
      antagonist HOE 140, injected over the paratrigeminal nucleus 30 min earlier,
      abolished the pressor response caused by bradykinin. 5. Low doses of bradykinin
      injected in or directly over the paratrigeminal nucleus increased arterial
      pressure and caused a small increase in heart rate by stimulating kinin receptors
      of the paratrigeminal nucleus in the dorsolateral medulla of awake and
      unrestrained rats. The pattern of the response was consistent with that of
      sympathetic stimulation. The paratrigeminal nucleus, which receives primary
      afferents and projects to the nucleus tractus solitarii and the rostral ventral
      lateral medulla, may be positioned as relay nucleus possibly connecting sensory
      input to structures that regulate blood pressure.

PMID- 9234202
TI  - Activity-dependent properties of synaptic transmission at two classes of
      connections made by rat neocortical pyramidal axons in vitro.
AB  - 1. To compare the dynamics of synaptic transmission at different types of
      connection, dual intracellular recordings were made from pairs of neurones in
      slices of adult rat neocortex. Excitatory postsynaptic potentials (EPSPs) were
      elicited by single spikes, spike pairs and brief spike trains in presynaptic
      pyramidal cells and responses recorded in postsynaptic pyramidal cells and in
      interneurones. 2. Pyramid-pyramid EPSPs were strongly voltage dependent and this
      resulted in a range of paired pulse effects. At thirty-two of sixty-nine pyramid
      pyramid connections, the 2nd EPSP was the same shape as the 1st, indicating
      minimal interaction between active synapses. In these thirty-two connections,
      paired pulse depression (PPD) was apparent (2nd EPSP integral 46 +/- 21% of the
      1st, at 5-20 ms), which recovered within 60-70 ms. 3. In eleven additional
      pyramid-pyramid pairs, the 2nd EPSP was also the same shape as the 1st, but
      paired pulse facilitation (PPF, 149 +/- 32%) decaying within 50-60 ms was
      apparent. Even these connections displayed frequency-dependent depression,
      however, as 3rd EPSPs were smaller than 1st EPSPs at intervals < 100 ms. 4. At
      twenty-five pyramid-pyramid connections, 2nd EPSPs were broader than 1st EPSPs
      and in sixteen of these, voltage- and NMDA receptor-dependent enhancement was
      large enough to obscure the underlying PPD. PPD was revealed by postsynaptic
      hyperpolarization (4 pairs), N-methyl-D-aspartate (NMDA) receptor blockade (3
      paris), or if Mg2+ was removed (in the one case studied). If synapse location
      allowed significant depolarization of one active site by another, voltage
      dependent enhancement could produce supralinear EPSP summation and overcome PPD.
      Third EPSPs were, however, consistently smaller than 1st EPSPs. 5. In striking
      contrast, profound frequency-dependent facilitation, independent of voltage or
      NMDA receptors was seen at fifteen connections involving two classes of
      postsynaptic interneurones. 6. At these pyramid-interneurone connections,
      facilitation of the 2nd EPSP (655 +/- 380% at 5-20 ms) decayed rapidly, within 50
      60 ms. Third and fourth EPSPs showed additional facilitation which decayed more
      slowly, within 90 ms and 2 s, respectively. Facilitation due to five to six spike
      trains was still apparent at 3 s. Therefore, once initiated by a brief high
      frequency spike train, facilitation was maintained at lower frequencies.

PMID- 9234203
TI  - Neurones in the supraoptic nucleus of the rat are regulated by a projection from
      the suprachiasmatic nucleus.
AB  - 1. In the rat, projections from the suprachiasmatic nucleus (SCN) to the
      supraoptic nucleus (SON) of the hypothalamus were characterized in vivo using
      extracellular recordings and in slice preparations using both extracellular and
      whole-cell patch clamp recording. 2. Of 117 magnocellular neurones recorded in
      the SON in vivo, fifteen (13%) displayed a short latency excitation, sixty-eight
      (58%) a short latency inhibition, six (5%) were unresponsive and twenty-eight
      (24%) gave long latency responses following SCN stimulation. 3. The responses of
      putative vasopressin cells in the SON to SCN stimulation in vivo (4 out of 61
      cells, 7% excited; 49 out of 61 cells, 80% inhibited) were significantly
      different from those of putative oxytocin cells (10 out of 50 cells, 20% excited
      and 16 out of 50 cells, 32% inhibited; P < 0.02, test for differences between
      proportions). 4. Recordings in vitro using patch technology in whole-cell mode
      showed both inward and outward currents in SON cells at holding potentials near
      resting membrane potential following stimulation of the SCN region. The outward
      currents could be blocked by bicuculline (10 microM; n = 7) and the inward
      currents were blocked by the non-NMDA antagonist 6-nitro-7
      sulphamoylbenzo(f)quinoxaline-2,3-dione (5 microM; n = 4). 5. We conclude that
      there is a strong projection from the SCN to the SON with both inhibitory
      (GABAergic) and excitatory (glutamatergic) components which may regulate the
      daily changes in neurohypophysial hormone secretion.

PMID- 9234205
TI  - Modulation of endogenous firing patterns by osmolarity in rat hippocampal
      neurones.
AB  - 1. Intracellular recordings in adult rat hippocampal slices were used to
      investigate the modulation of endogenous neuronal firing patterns by moderate
      changes (+/-13%) in the extracellular osmotic pressure (pi o). The responses of
      CA1 pyramidal cells to graded depolarizing current pulses were used to
      differentiate between regular and burst-firing patterns and to characterize the
      stimulus requirements for evoking endogenous burst discharge. 2. Decreasing or
      increasing pi o had no significant effects on resting membrane potential and
      input resistance, spike threshold and amplitude, and the amplitudes of the fast,
      medium and slow spike after-hyperpolarizations (AHPs). The apparent membrane time
      constant (tau m) increased in low pi o and decreased in high pi o. 3. Reducing pi
      o converted non-bursting neurones (non-bursters) to bursting neurones (bursters)
      and decreased the stimulus requirements for evoking burst firing in native
      bursters. Increasing pi o suppressed endogenous burst firing. 4. Lowering pi o
      increased the size of the 'active' (i.e. re-depolarizing) component of the spike
      after-depolarization (ADP). Conversely, increasing pi o suppressed the active ADP
      component. 5. The sensitivity of spike ADPs and firing patterns of pyramidal
      cells to the changes in pi o persisted also in Ca(2+)-free saline, indicating
      that the osmotic effects are not imparted by modulation of Ca2+ and/or Ca(2+)
      activated K+ currents. 6. Blocking most K+ currents with Ca(2+)-free, TEA
      containing saline induced large and prolonged (up to 1 s), TTX-sensitive plateau
      potentials following the primary fast spikes. These potentials were augmented by
      low pi o and abated by high pi o. 7. When injected with subthreshold depolarizing
      current pulses in Ca(2+)-free saline, pyramidal cells displayed a distinct TTX
      sensitive inward rectification. This rectification was augmented by low pi o and
      reduced by high pi o. 8. The various effects of low-pi o and high-pi o saline
      solutions were reversible upon washing with normosmotic saline. 9. We conclude
      that pi o is a critical determinant of the endogenous firing patterns of CA1
      pyramidal cells. The data suggest that the osmotic effects are most likely to be
      mediated by changes in the persistent Na+ current, which underlies the active
      spike ADP and the burst potential in CA1 pyramidal neurones. The possible
      contribution of these effects to changes in brain excitability in various
      abnormal osmotic states in discussed.

PMID- 9234206
TI  - Bilateral disruption of conditioned responses after unilateral blockade of
      cerebellar output in the decerebrate ferret.
AB  - 1. Lesions of the cerebellar cortex can abolish classically conditioned eyeblink
      responses, but some recovery with retraining has been observed. It has been
      suggested that the recovered responses are generated by the intact contralateral
      cerebellar hemisphere. In order to investigate this suggestion, bilaterally
      acquired conditioned responses were studied after the unilateral blockade of
      cerebellar output. 2. Decerebrate ferrets were trained with ipsilateral
      electrical forelimb stimulation (300 ms, 50 Hz, 1 mA) as the conditioned stimulus
      and bilaterally applied peri-orbital stimulation (40 ms, 50 Hz, 3 mA) as the
      unconditioned stimulus. The conditioned and unconditioned eyeblink responses were
      monitored by EMG recordings from the orbicularis oculi muscle. The output from
      one cerebellar hemisphere was blocked either by injecting small amounts of
      lignocaine (lidocaine; 0.5-1.0 microliter) into the brachium conjunctivum, or by
      a restricted mechanical lesion of the brainstem rostral to the cerebellum. 3. As
      described by previous investigators, the unilateral blockade of cerebellar output
      abolished ipsilateral conditioned responses. 4. More importantly, such blockade
      also abolished or strongly depressed contralateral conditioned responses. When
      mechanical lesions of the brachium conjunctivum were made, contralateral
      responses, in contrast to ipsilateral responses, recovered within 1-2.5 h. 5.
      When the unconditioned stimulus was removed on one side, causing extinction of
      conditioned responses on this side, conditioned responses were temporarily
      depressed on the trained side as well. 6. Unilateral interruption of cerebellar
      output had no clear effect on contralateral unconditioned reflex responses. 7.
      The results demonstrate that one cerebellar hemisphere in ferrets exerts a marked
      control of contralateral conditioned eyeblink responses, probably via premotor
      neurones involved specifically in conditioned, and not in unconditioned,
      responses.

PMID- 9234204
TI  - Mechanism of oxidative stress-induced intracellular acidosis in rat cerebellar
      astrocytes and C6 glioma cells.
AB  - 1. Following ischaemic reperfusion, large amounts of superoxide anion (.O2-),
      hydroxyl radical (.OH) and H2O2 are produced, resulting in brain oedema and
      changes in cerebral vascular permeability. We have found that H2O2 (100 microM)
      induces a significant intracellular acidosis in both cultured rat cerebellar
      astrocytes (0.37 +/- 0.04 pH units) and C6 glioma cells (0.33 +/- 0.07 pH units).
      2. Two membrane-crossing ferrous iron chelators, phenanthroline and deferoxamine,
      almost completely inhibited H2O2-induced intracellular acidosis, while the non
      membrane-crossing iron chelator apo-transferrin had no effect. Furthermore, the
      acidosis was completely inhibited by two potent membrane-crossing .OH scavengers,
      N-(2-mercaptopropionyl)-glycine (N-MPG) and dimethyl thiourea (DMTU). Since .OH
      can be produced during iron-catalysed H2O2 breakdown (Fenton reaction), we have
      shown that a large reduction in pH1 in glial cells can result from the production
      of intracellular .OH via H2O2 oxidation. 3. We have ruled out the possible
      involvement of: (i) an increase in intracellular Ca2+ levels; and (ii) inhibition
      of oxidative phosphorylation. 4. Our results suggest that .OH inhibits
      glycolysis, leading to ATP hydrolysis and intracellular acidosis. This conclusion
      is based on the following observations: (i) in glucose-free medium, or in the
      presence of iodoacetate or 2-deoxy-D-glucose, H2O2-induced acidosis is completely
      suppressed; (ii) H2O2 and iodoacetate both produce an increase in levels of
      intracellular free Mg2+, an indicator of ATP breakdown; and (iii) direct
      measurement of intracellular ATP levels and lactate production show 50 and 55%
      reductions in ATP content and lactate production, respectively, following
      treatment with 100 microM H2O2. 5. Inhibition of the pH1 regulators (i.e. the
      Na(+)-H+ exchange and possibly the Na(+)-HCO3(-)-dependent pH1 transporters)
      resulting from H2O2-induced intracellular ATP reduction may also be involved in
      the H2O2-evoked intracellular acidosis in glial cells.

PMID- 9234207
TI  - Gating of cutaneous input to cerebellar climbing fibres during a reaching task in
      the cat.
AB  - 1. Task-dependent modulation of cutaneous input to climbing fibres projecting to
      the C1, C2 and C3 zones in the cerebellar paravermal lobule V was investigated in
      awake cats during performance of a reaching task. 2. Climbing fibre responses
      resulting from low intensity (non-noxious) electrical stimulation of the
      ipsilateral superficial radial nerve were recorded as extracellular field
      potentials in the cerebellar cortex using chronically implanted microwires. 3.
      Response size, measured as the time-voltage integral of the evoked field
      potential, was assessed during three phases of the reaching movement, reaction,
      reach and grasp, and compared with the response size at rest. 4. At C1 and C3
      zone recording sites response size was usually reduced during the task (7/10
      sites). The reduction was most pronounced in the grasp phase, occasionally
      accompanied by a smaller reduction in the reach and reaction phases. In one case
      an enhancement was found in the reach phase. 5. Response size was also modulated
      during the task at four of six C2 zone recording sites. However, the results were
      mixed. In three cases the modulation resembled the pattern at C1/C3 sites with
      the responses being reduced in the grasp phase accompanied on occasion by a
      lesser reduction in the reach phase. In the remaining case there was an
      enhancement during grasp. In this case and one other there was also an
      enhancement during the reaction phase. 6. The findings indicate significant
      gating of cutaneous input to climbing fibres projecting to the C1, C2 and C3
      zones during reaching movements, while the variability between recording sites
      suggests functional differences, both between and within zones.

PMID- 9234208
TI  - Perception and gut reflexes induced by stimulation of gastrointestinal
      thermoreceptors in humans.
AB  - 1. Experimental studies in animals suggest the existence of thermoreceptors in
      the gastrointestinal tract. Our aim was to investigate the distribution and
      specificity of upper gut thermoreceptors in humans. 2. In healthy subjects,
      thermal stimulation of the stomach (n = 8) and the small intestine (n = 6) was
      produced by means of a thermostat, which recirculates water at adjusted
      temperatures through an ultrathin intraluminal bag. Progressively warm (42, 47
      and 52 degrees C) and cold (32, 22 and 12 degrees C) stimuli of 3 min duration
      were alternately applied at 13 min intervals. Perception was scored on a scale of
      0-6 and gastric tone responses were measured with a barostat. 3. Thermal stimuli
      induced specific responses: cold stimuli induced abdominal cold sensation and a
      reflex contraction of the stomach, whereas warm stimuli induced warm sensation
      and a reflex gastric relaxation. 4. Thermal stimuli induced similar stimulus
      related perception in the stomach and small intestine (temperatures between 12
      and 49.5 +/- 0.5 degrees C were tolerated). 5. The reflex responses were site
      specific. Warm and cold stimulation of the stomach induced gastric reflexes (76
      +/- 26 ml isobaric expansion at 47 degrees C, and 68 +/- 10 ml contraction at 12
      degrees C; P < 0.05 for both). However, only warm, not cold, stimulation of the
      intestine induced enterogastric reflexes. 6. These results indicate that in
      humans, warm and cold receptors are distributed along the gastrointestinal tract
      and project afferent input both into perception and reflex circuits with specific
      topographic organization.

PMID- 9234210
TI  - Uterine stromal cell suppression of pIgR production by uterine epithelial cells
      in vitro: a mechanism for regulation of pIgR production.
AB  - Previous studies have shown that the polymeric Ig receptor (pIgR) is produced by
      rat uterine epithelial cells both in vivo and vitro. The expression of the pIgR
      is regulated by sex hormones and/or cytokines at mucosal sites, however the
      mechanism of regulation in the uterus is not clear. In these studies, co-culture
      of stromal cells from mature rat uteri with uterine epithelial cells decreased
      epithelial cell pIgR production. Conditioned supernatants from stromal cells
      incubated with epithelial cells also decreased pIgR production.
      Immunohistochemical studies confirmed that expression of pIgR on uterine
      epithelial cells decreased in the presence of stromal cells. Viability of
      epithelial cells was sustained during these experiments, as evidenced by the
      maintenance of high transepithelial resistance. These studies are the first
      report of stromal cell regulation of pIgR production by epithelial cells at any
      site in the body and suggest that stromal cells can provide a signal that leads
      to the regulation of pIgR production.

PMID- 9234209
TI  - The contribution of otoliths and semicircular canals to the perception of two
      dimensional passive whole-body motion in humans.
AB  - 1. Perception of two-dimensional (2-D) whole-body passive motion in the
      horizontal plane was studied in twelve blindfolded healthy volunteers: pure
      rotation in place (180 deg), linear motion (4.5 m) and a semicircular trajectory
      (radius, 1.5 m; angular acceleration, 0.2 rad s-2) were applied in random
      sequence by means of a remote-controlled robot equipped with a racing-car seat.
      The seat orientation in the horizontal plane was controlled by the experimenter,
      independent of the robot trajectory. Thus different degrees of otolith-canal
      interaction were obtained. The maximal linear acceleration during the
      semicircular trajectory was 0.1 g; however, the linear acceleration vector was
      complex as it rotated relative to the subject's head. 2. In the first of two
      sessions, subjects were instructed to maintain an angular pointer oriented
      towards a remote (15 m) previously seen target during the passive movements. In
      the second session they had to make a drawing of the path of the perceived
      trajectory, after the movement was finished. 3. The results showed that, on
      average, the movement of the pointer matched the dynamics of the rotatory
      component of the 2-D motion well. This suggests that, in the range of linear
      accelerations used in this study, no appreciable influence of otolith input on
      canal-mediated perception of angular motion occurred. 4. The curvature of the
      drawn paths was mostly explained by the input to the semicircular canals.
      Subjects' reconstruction of motion did not account for the directional dynamics
      of the input to the otoliths occurring during passive motion. 5. This finding
      proves that reconstructing trajectory in space does not imply a mathematically
      perfect transformation of the linear and angular motion-related inputs into a
      Cartesian or polar 2-D representation. Physiological constraints on the
      interaction between motion direction and change of heading play an important role
      in motion perception.

PMID- 9234211
TI  - Induction of native protein reactive antibodies by immunization with peptides
      containing linear B-cell epitopes defined by anti-porcine ZP3 beta monoclonal
      antibodies.
AB  - To identify pertinent target epitopes for contraceptive vaccine development,
      rabbit polyclonal antibodies were raised against four peptides synthesized from
      the deduced amino acid (aa) sequence of porcine zona pellucida macromolecule ZP3
      beta and coupled to diphtheria toxoid (DT). Synthetic peptides consisted of: P1,
      23-37 aa; P2, 164-179 aa with an additional C-terminal cysteine; P3, 246-263 aa
      with an extra C-terminal cysteine; and P4, 310-321 aa residues corresponding to
      pZP3 beta precursor protein. Selected sequences were based upon B cell epitopes
      identified previously by monoclonal antibodies. Immune sera reacted with their
      respective peptides and DT in an ELISA, and also recognized porcine SIZP and pZP3
      beta both in ELISA and Western blot and zona pellucida of porcine oocytes in an
      indirect immunofluorescence assay. None of the four anti-peptide sera recognized
      pZP3 alpha in Western blot, emphasizing the specificity of these antibodies to
      pZP3 beta. The anti-peptide sera, individually, failed to inhibit in vitro
      attachment of boar sperm to antibody treated zona encased porcine oocytes.
      However, combinations of immune sera against peptides such as P1 + P4, P2 + P4
      and P1 + P2 + P4, did significantly inhibit porcine sperm-oocyte interaction.
      These results identify combinations of peptides that could potentially be used in
      the design of an immunocontraceptive vaccine based upon synthetic peptides
      corresponding to pZP3 beta or its homologues in other species.

PMID- 9234212
TI  - Appearance of 'natural' antisperm autoantibodies after sexual maturation of
      normal Lewis rats.
AB  - Serum antisperm antibodies were assessed quantitatively with an ELISA in normal
      male Lewis rats at intervals between ages 10 and 128 days, spanning the onset of
      puberty. Antisperm antibodies rose between 56 and 91 days, and were significantly
      higher in 91- and 128-day old rats than at earlier intervals. The animals
      underwent normal pubertal development as indicated by increases in weights of the
      seminal vesicles and ventral prostate. The rise in antisperm antibodies
      correlated temporally with events in the postnatal development of the male
      reproductive system, with the increase in antisperm antibodies most closely
      following the time when spermatozoa reach the epididymis and proximal vas
      deferens at approximately 56 days. The observation that serum antisperm
      antibodies increased only after sexual maturation suggests that some
      differentiation antigens of sperm are processed and presented to the immune
      system under normal circumstances in this strain. Western blot analysis showed
      that the sera from normal postpubertal Lewis rats bound several proteins,
      including bands of > 100, 82-75, 78, 68, 65, 63, 54-55, 42, 37, 35, 26, and 20-22
      kDa. The majority of these autoantibodies were sperm-specific as shown by the
      absence of comigrating bands in western blots of somatic tissue extracts,
      although antibodies in postpubertal sera recognized certain other proteins in
      somatic tissues. Several protein autoantigens, defined by sera from postpubertal
      animals, matched dominant autoantigens recognized by antibodies produced in
      response to vasectomy, prepubertal vas obstruction, or immunization with
      spermatozoa. This finding indicates that the antisperm antibody responses
      following sperm immunization, vasectomy or prepubertal vasal obstruction
      represent accentuation of an autoantibody response to sperm that develops
      normally following puberty.

PMID- 9234213
TI  - Amniotic fluid interleukin-10 (IL-10) concentrations during pregnancy and with
      labor.
AB  - To determine if amniotic fluid interleukin-10 (IL-10) concentrations are elevated
      in women with labor, either at term or preterm, and in the setting of infection
      associated preterm labor, amniotic fluid samples were collected from women: (1)
      at term, not in labor (n = 42); at term, in labor (n = 56), preterm contractions,
      undelivered within 1 week (n = 22), and preterm labor, delivered within 1 week (n
      = 31). IL-10 concentrations were assayed in each sample via ELISA (Pharmingen,
      San Diego, CA). In a subsequent analysis, 8 women with preterm labor associated
      with chorioamnionitis were matched for gestational age with women experiencing
      preterm contractions (undelivered within 7 days) and preterm labor (delivered
      within 7 days) and amniotic fluid IL-10 concentrations compared. Approximately 40
      70% of amniotic fluid samples obtained from women in each group had detectable IL
      10. However, there were no significant differences in amniotic fluid IL-10
      concentrations among the patients. While 1 of 8 patients with chorioamnionitis
      had amniotic fluid IL-10 concentrations greater than 300 pg/ml, there were no
      statistically significant differences among the matched samples. Amniotic fluid
      IL-10 concentrations were not elevated in women with term labor, preterm labor,
      or chorioamnionitis. This finding contrasts with the elevated concentrations of
      pro-inflammatory cytokines and chemokines such as interleukin-1, tumor necrosis
      factor-alpha, IL-6, IL-8, MIP-1 alpha, and GRO alpha reported in previous
      studies. Because we did not detect elevations of the key anti-inflammatory
      cytokine IL-10 in amniotic fluid of women with infection-associated preterm
      labor, we suggest that anti-inflammatory processes in this setting may be
      attenuated.

PMID- 9234215
TI  - Measurement of reverse transcriptase of feline immunodeficiency virus by poly A
      linked colorimetric assay.
AB  - The method of the poly A-linked colorimetric reverse transcriptase assay (PAC
      RTA) was developed and evaluated for the measurement of Mg(2+)-dependent reverse
      transcriptase (RT) activity of feline immunodeficiency virus (FIV). PAC-RTA was
      first evaluated for the detection of RT activity in the culture supernatant of
      FIV Petaluma strain. The detection limit of RT activity by PAC-RTA was about 10
      fold better than that by the conventional non-radioisotopic RT assay kit. Then,
      PAC-RTA was evaluated for the indication of FIV isolation from cats naturally
      infected with FIV. FIV was isolated from peripheral blood mononuclear cells of 9
      FIV-seropositive cats. The time course appearance of RT activity measured by PAC
      RTA corresponded with the analysis of FIV antigen expression by indirect
      immunofluorescence. Finally, PAC-RTA evaluated the drug susceptibility of FIV.
      MYA-1 cells (feline T-lymphoblastoid cells) were infected with FIV and were
      cultured in the presence of various concentrations of anti-human immunodeficiency
      virus agents such as azidothymidine (AZT) or dextran sulfate. An inverse
      relationship between the RT activities and the concentrations of these agents in
      the culture supernatant was confirmed by PAC-RTA. PAC-RTA is easy to perform
      without using radioactive materials, and one plate can handle 96 samples at one
      time. By monitoring the RT activity, this assay is a useful method for FIV
      studies such as viral replication and drug susceptibility.

PMID- 9234214
TI  - Immunologic activation during pregnancy: serial measurement of lymphocyte
      phenotype and serum activation molecules in HIV-infected and uninfected women.
AB  - Immunologic alterations occur during pregnancy, but the effect of pregnancy on
      HIV infection is controversial. We characterized some of the immunologic
      alterations with potential to influence HIV disease in 99 infected and 46
      uninfected women during pregnancy and up to 6 months post-partum.
      Immunophenotyping to quantitate the major lymphocyte subsets and determine
      expression of activation and adhesion molecules on T cells was performed using 3
      color staining and laser flow cytometry. Serum neopterin, beta 2-microglobulin,
      and tumor necrosis factor-alpha (TNF alpha) were quantitated using commercial
      immunoassays. HIV + pregnant women were compared to uninfected pregnant subjects
      and to reference ranges established on healthy, HIV-seronegative non-pregnant
      female controls. Both CD4 and CD8 T cell subsets were increased in HIV-negative
      pregnant women compared to non-pregnant controls. In HIV-infected pregnant women,
      CD4 T cells were low and CD8 cells were elevated compared to HIV-negative
      pregnant and non-pregnant women. Levels of subsets were stable during pregnancy
      and postpartum in both groups of women. Evidence of peripheral immune activation
      was found during the later stages of pregnancy. Increases in HLA-DR and CD38
      activation antigens on CD8 cells, serum neopterin and beta-2-microglobulin were
      seen during pregnancy in HIV-negative women. These correlates of immune
      activation were increased in HIV-infected pregnant women and increased further
      during pregnancy, paralleling changes seen in uninfected pregnant women. These
      immunologic alterations may directly or indirectly enhance viral replication,
      impacting the long-term course of HIV disease.

PMID- 9234216
TI  - Structural organization and chromosomal assignment of the swine endothelin-1
      gene.
AB  - Cosmid clone containing swine endothelin-1 (EDN1) gene, cosEDN1, was isolated
      from swine cosmid library using swine EDN1 cDNA as a probe. The sequence analysis
      of cosEDN1 DNA revealed that the swine EDN1 gene consists of 5 exons, spanning
      approximately 6.5 kb. In the 5'-upstream region of the EDN1 gene, AP-1 and NF-1
      elements were found, suggesting the possibility that the expression of swine EDN1
      gene is controlled by protooncogene products Fos and Jun, and TGF-beta.
      Fluorescence in situ hybridization (FISH) using cosEDN1 DNA as a probe
      demonstrated that EDN1 gene resides on swine chromosome 7p13- > pter.

PMID- 9234217
TI  - Detection of interleukin-1 beta in sera and colostrum of dairy cattle and in sera
      of neonates.
AB  - In order to obtain basic information about bovine interleukin-1 (IL-1 beta),
      levels of IL-1 beta in sera and milk of clinically normal mature Holstein cattle
      before and after parturition and in sera of newborn calves were examined by
      ELISA. The level of IL-1 beta was undetectable in sera of mature cattle around
      the time of artificial insemination, but the concentration gradually increased
      and reached a peak at parturition and then decreased again to an undetectable
      level. IL-1 beta in milk was detected on the day of parturition but not
      thereafter. IL-1 beta mRNA was detected by reverse transcription-polymerase chain
      reaction in the cells from milk collected during 20 days before and 2 to 3 days
      after parturition, but was not detected thereafter. Although IL-1 beta was not
      detected in all the sera of newborn calves, the concentration transiently
      increased with peak titers on day 3 and became undetectable by day 14 after
      birth. Newborns that showed serum IL-1 beta on day 3 had been fed on colostrum in
      which the IL-1 beta concentration was significantly higher than that in colostrum
      that had been fed to newborns having no detectable IL-1 beta on day 3. These
      results indicate that IL-1 beta is induced in association with pregnancy in
      healthy dairy cattle and that the cytokine might be transferred to neonates via
      colostrum.

PMID- 9234218
TI  - Pulsed-field gel electrophoresis of Staphylococcus hyicus and Staphylococcus
      chromogenes genomic DNA and its taxonomic, epidemiologic and ecologic
      applications in veterinary medicine.
AB  - One hundred and thirty-eight strains of Staphylococcus hyicus and 21 strains of
      S. chromogenes isolated from animals were analyzed by pulsed-field gel
      electrophoresis (PFGE) after restriction endonuclease Smal digestion of
      chromosomal DNA. Eighty-eight strains of S. hyicus from pigs with or without
      exudative epidermitis (EE) generated 16 to 26 fragments in the size range of < 1
      to 485 kb, and yielded 39 different patterns. With regard to the strains from
      pigs with EE, PFGE patterns differed according to the country of origin.
      Outbreaks of EE occurring on four separate pig farms in Japan involved S. hyicus
      with different PFGE patterns. The PFGE patterns shown by S. hyicus strains from 4
      kinds of animals were compared. Strains from pigs differed from those isolated
      from chickens (n = 45; 18 to 24 fragments of < 1 to 425 kb), cows (n = 3; 17 to
      19 fragments of < 1 to 475 kb), and goats (n = 2; 16 or 17 fragments of < 1 to
      1,125 kb). Also, each of the chicken, cow and goat strains had a host-specific
      fragment. The results suggest that PFGE analysis might be a useful marker for
      distinguishing ecovars within S. hyicus. In contrast, strains of S. chromogenes
      from pigs and cows generated 17 to 24 fragments ranging from < 1 to 545 kb. The
      PFGE patterns of S. chromogenes strains were more highly conserved than those of
      S. hyicus. S. chromogenes strains could be distinguished from S. hyicus strains
      by fragments within the range of 305 to 545 kb. The results indicate that PFGE
      analysis could be used to distinguish between S. hyicus and S. chromogenes. We
      conclude that PFGE analysis is a useful tool not only for species or strain
      identification but also for epidemiologic or ecologic studies of S. hyicus and S.
      chromogenes.

PMID- 9234219
TI  - Effects on endotoxin pathogenicity in pigs with acute septicemia of Haemophilus
      parasuis infection.
AB  - Changes of endotoxin in plasma, and the response of the coagulation system and
      blood cells in septicemia of Haemophilus parasuis infection were examined by
      inoculation with H. parasuis in specific pathogen-free (SPF) pigs. Eight pigs
      were inoculated intratracheally with 10(5), 10(6) and 10(7) colony formation
      units (CFU) of the strain Nagasaki (serovar 5). All pigs died 28 to 42 hr after
      inoculation. Haematologically, severe leukopenia occurred 24 hr post inoculation
      (hpi) until death. Glucose concentration decreased from 24 hpi to death. In the
      coagulation system, decrease of platelet counts, prolongation of prothrombin
      time, activated partial thromboplastin time, and increase of fibrinogen-fibrin
      degradation products were observed in all inoculated pigs. Endotoxin was detected
      in the plasma of all the inoculated pigs from 16 hpi to death, and its
      concentration rose dramatically just before death. H. parasuis was re-isolated
      from the blood of all inoculated pigs from 16 hpi to death, and also from almost
      all organs and body fluids of the pigs. The pigs had microthrombi in the kidney,
      liver and lungs, and many also had pneumonia, meningitis and serositis. H.
      parasuis antigen was detected in the lesions by the immunoperoxidase technique.
      The results indicated that disseminated intravascular coagulation (DIC) and
      endotoxin shock involved aggravation of clinical signs and death on the pigs
      induced to septicemia of H. parasuis.

PMID- 9234220
TI  - Current status of animal rabies in Thailand.
AB  - Canine rabies remains a serious public health problem in Thailand. The Queen
      Saovabha Memorial Institute (QSMI) is the principal rabies diagnostic center in
      central Thailand. The retrospective study of canine rabies cases submitted in
      1992-1995 revealed that: (1) The prevalence of rabid dogs decreased, which was
      associated with an overall decrease in the number of animals examined. However,
      the proportion of FA positive dogs examined remains the same at approximately
      50%. (2) The majority of rabies cases occurred in domestic dogs rather than stray
      dogs but the ratio of positive cases between domestic and stray animals remained
      the same. (3) More than 60% of domestic rabid dogs were below age one. Dogs at
      this age are thought to be more active and also most likely not adequately
      vaccinated. It should be noted that approximately 70% of rabid dogs were never
      vaccinated against rabies.

PMID- 9234221
TI  - Isolation of mycoplasmas from fantail pigeons.
AB  - Isolation of mycoplasmas from the oropharynxes of 60 fantails reared under
      natural conditions at different zoological parks in Miyazaki prefecture was
      carried out. Mycoplasma columbinum, M. columborale and M. columbinasale were
      isolated from 28 (46.7%), 22 (36.7%), and 1 (1.7%) of 60 oropharynxes,
      respectively, but no Mycoplasma was isolated from 5 cloacas tested. Ureaplasma
      was not isolated from any of the 28 oropharynxes or 5 cloacas examined. We report
      that 41 (68.3%) of 60 fantails had one or two species of mycoplasmas in their
      oropharynxes, and make the first confirmation of M. columbinasale inhabiting a
      Japanese pigeon.

PMID- 9234222
TI  - Induction of luteinizing hormone surge by pulsatile administration of
      gonadotropin-releasing hormone analogue in cows with follicular cysts.
AB  - LH release in response to pulsatile administration of small amounts of GnRH
      analogue in cows with follicular cysts was examined. The pulsatile administration
      of GnRH analogue induced a LH-surge like peak over 10 hr in both normal cows and
      cows with follicular cysts. The mean peak value of LH in follicular cystic cows
      did not differ significantly from that of normal cows. All the cows with cysts
      resumed normal estrous cycles with ovulations within 3 weeks of this treatment.
      These results suggest that the function of the anterior pituitary for LH release
      in response to GnRH analogue is not abnormal in cows with follicular cysts, and
      that cystic cows recover to normal conditions after the pulsatile administration
      of GnRH analogue.

PMID- 9234223
TI  - Generation of monoclonal antibodies against a feline CD antigen (CD4) expressed
      by a recombinant baculovirus.
AB  - We attempted to establish a system to generate monoclonal antibodies (mAbs)
      recognizing CD antigens on lymphocytes of domestic animals using the expressed CD
      antigens by a baculovirus expression system. For this purpose, we selected feline
      CD4 (fCD4) antigen and expressed it in an insect cell line (Sf9 cells). To obtain
      mAbs, BALB/c mice were immunized with feline peripheral blood mononuclear cells
      (fPBMCs) or Sf9 cells expressing the fCD4 (Sf-fCD4 cells), and then hybridomas
      secreting antibodies were screened by indirect immunofluorescence assay against
      the opposite antigens of Sf-fCD4 cells or fPBMCs, respectively. Five mAbs
      recognizing the fCD4 were obtained in total. The system established here might be
      useful to obtain mAbs recognizing CD antigens of domestic animals.

PMID- 9234224
TI  - Metabolic alkalosis in coliform mastitis.
AB  - Values of blood gas, serum chloride, and potassium were tabulated for 21 dairy
      cows with coliform mastitis. Severe cases showed marked clinical signs such as
      loss of appetite and depression of digestive tract motility, and metabolic
      alkalosis such as an increase in blood pH, hypochloremia and hypokalemia compared
      with normal and mild cases (p < 0.01). The results showed that metabolic
      alkalosis can be detected more easily than acidosis in cases of severe coliform
      mastitis.

PMID- 9234225
TI  - Distribution of motoneurons innervating tail muscles in the pigeon.
AB  - The distribution of motoneurons innervating the tail muscles, M. levator caudae,
      M. depressor caudae, M. pubocaudalis externus, M. pubocaudalis internus, M.
      lateralis caudae and M. flexor cruris, in the adult pigeon was examined by
      retrograde transport of horseradish peroxides. Labeled motoneurons innervating
      tail muscles were distributed in the longitudinal column of the spinal cord below
      the sacral spinal segment 5. The average diameter of cell bodies ranged from 23.7
      to 62.5 microns. Each motoneuron pool was localized in a characteristic position
      in the ventral horn.

PMID- 9234226
TI  - Relation between daily urinary creatinine and body weight in castrated male
      Landrace pigs.
AB  - For clarifying the relation between the amount of daily urinary creatinine (Cr)
      and the body weight (BW), fifty-eight healthy castrated male Landrace pigs
      ranging from 28.6 kg to 93.5 kg in body weight (BW) were examined. There was a
      significant positive correlation between the BW (X = kg) and Cr (Y = mg/day), and
      a linear regression formula of Y = 40.7X-224.9 (R2 = 0.985, P < 0.001) was
      obtained. The coefficient of variation of the daily urinary Cr was small (5.1 +/-
      2.4%). On the other hand, in the relation between the BW and quantity of urine in
      24 hr, and in the relation between the daily urinary creatinine and daily urinary
      volume, no significant correlation was recognized (P > 0.2), respectively.

PMID- 9234228
TI  - Evaluation of blood acid-base balance after experimental administration of
      endotoxin in adult cow.
AB  - Esherichia coli endotoxin was administered intravenously to 7 Holstein adult
      cows, to evaluate the effect of endotoxin on acid-base balance. Endotoxin shock
      was observed immediately after the administration of endotoxin. A loss of
      appetite and depression of digestive tract motility continued for about 120 hr
      after the challenge. Metabolic alkalosis following hypochloremia and hypokalemia
      were particularly pronounced at 12 to 72 hr after the administration of
      endotoxin.

PMID- 9234227
TI  - Improved in vitro cultivation of Babesia caballi.
AB  - Babesia caballi infected erythrocytes were collected from the blood of an
      experimentally infected horse and could be continuously cultivated in vitro with
      parasitemia ranging from 2-4% in RPMI 1640 medium supplemented with 2 mM L
      glutamine, 20 mM HEPES and 40% adult horse serum in a low oxygen atmosphere (2%
      O2, 5% CO2 and 93% N2). All attempts to increase parasitemia failed using other
      culture media, serum concentrations and culture vessels. However, parasite growth
      was enhanced by transfer of cultures from a low oxygen to 5% CO2 in air, with
      parasitemia ranging from 8-10%.

PMID- 9234229
TI  - Survival of mycoplasmas inoculated in horse sera.
AB  - Although it is known that commercialized bovine serum is sometimes contaminated
      with mycoplasmas, it is not clear whether mycoplasmas can survive in horse serum.
      In this study, as a preliminary examination of the survival of mycoplasmas
      inoculated in horse sera, the survivability of 8 strains of 7 mycoplasmas was
      tested. The results obtained reveal that two strains of M. bovis and M.
      gallisepticum were found to survive in non-heated and inactivated sera for 94 to
      330 days at 30 or 37 degrees C. Three strains of M. bovirhinis, M. gateae and A.
      laidlawii lived for 7 to 330 days depending upon the temperature maintained or pH
      of the serum. Strains of M. bovigenitalium and U. diversum survived for a maximum
      of 8 days in all horse sera tested. Therefore, mycoplasmas are generally likely
      to survive for a long period in horse serum although the survival period depends
      on the species, strain and temperature.

PMID- 9234230
TI  - Sensitive enzyme-linked immunosorbent assay (ELISA) to measure parasite-specific
      antibodies of Indian soft-furred rats, Millardia meltada.
AB  - Immunoglobulin G (IgG) of Indian soft-furred rat, Millardia meltada, was purified
      by an immunoaffinity chromatography and antibodies against it was raised in
      rabbit. Using this rabbit anti-M. meltada IgG antibody, sensitivity of enzyme
      linked immunosorbent assay (ELISA) to measure parasite-specific antibodies in the
      sera of M. meltada was markedly enhanced than the previous method using rabbit
      anti-mouse IgG and rabbit anti-rat IgG antibodies, which could cross-react to M.
      meltada IgG. Since M. meltada could effectively produce circulating antibodies
      against two intestinal helminths, Strongyloides venezuelensis and Nippostrongylus
      brasiliensis, the high susceptibility of this animal to an array of parasites
      seems to be not due to general immunological deficiency.

PMID- 9234232
TI  - Fiber composition of the superior laryngeal nerve in rats and guinea pigs.
AB  - The fiber composition of the superior laryngeal nerve (SLN) which is served as
      the laryngeal afferent pathway was clarified in rats and guinea pigs. The
      proportions of the number of myelinated and unmyelinated fibers in the SLN were
      almost the same in both rats and guinea pigs. The unmyelinated fibers show the
      peak distribution of axon diameter ranging from 0.79 to 1.00 micron in both
      species, whereas the peak distribution of myelinated fibers ranged from 2.51 to
      3.16 microns in rats and from 3.98 to 5.01 microns in guinea pigs. The mean axon
      diameter of unmyelinated fibers was significantly larger in rats (mean: 1.12
      microns) than in guinea pigs (0.96 micron), whereas that of myelinated fibers was
      significantly larger in guinea pigs (4.04 microns) than in rats (3.30 microns).
      Such findings would reflect the cardiopulmonary reflexes elicited from the larynx
      in these animal species.

PMID- 9234231
TI  - Incidence of dogs possessing red blood cells with high K in Japan and East Asia.
AB  - The phenotype of high K (HK) red blood cells, which is an autosomal recessive,
      was found in dog groups from 10 of 13 breeds or populations in Japan. The
      incidence of HK was 26 to 38% in the San'in-Shiba, Shinshu-Shiba and Akita
      breeds, and the gene frequencies of HK ranged from 0.513 to 0.612. The highest
      incidence (42%) was found in the Jindo breed from Korea, and the gene frequency
      was 0.652. Two other groups from Korea also possessed this HK variation. However,
      although HK cells were not found in dogs from Taiwan, Indonesia, Mongolia and
      Sakhalin, Russia, the HK phenotype is clearly distributed now throughout Japan
      and Korea.

PMID- 9234233
TI  - Aging and the dendritic morphology of the rat laterodorsal and pedunculopontine
      tegmental nuclei.
AB  - The morphological appearance and quantitative parameters characterizing the
      dendrites of NADPH-diaphorase-stained neurons in the laterodorsal (LDT) and
      pedunculopontine (PPN) tegmental nuclei of 3-, 12- and 26-month-old rats were
      studied. All dendritic segments were classified according to the number of
      terminal and link segments they drain and the vertex analysis was used to
      quantify the dendritic tree and to determine its configuration. Morphological
      aberrations of the dendrites as local swelling, nodulation, thinning, shrinkage,
      folding and even the appearance of stumps were observed with advancing age. The
      quantitative analysis demonstrated a significant reduction (one-way ANOVA) of the
      total dendritic length, mean terminal path length, maximal segment length, total
      segment number and number of terminal segments at the rostral two thirds of the
      LDT and in the PPN. The mean vertex path length and the mean segment length
      significantly decreased only at the rostral level of the LDT. Plotting of the
      segment length against equivalent orders showed a decrease in all generations of
      the dendritic segments. The vertex ratios remained constant and indicated that
      the configuration of the dendritic tree remained unchanged during aging. The
      alterations in the dendrites mainly developed after 12 months of age. The age
      related changes in the morphology and quantitative parameters of the dendrites in
      the rostral two thirds of the LDT and PPN were rather similar, which could be
      explained by the common anatomical, neurochemical and electrophysiological
      features. Thus, the present results suggest a mild, but continuous regression of
      the dendritic tree of the rat LDT and PPN in normal aging.

PMID- 9234234
TI  - Blood lipoproteins and their effect on contractile function of vessels in rats of
      different age.
AB  - Experiments on adult and old rats have shown that blood lipoproteins (LP) exert a
      dilatatory effect on isolated-segments of the thoracic aorta in animals of
      different age. In old versus adult animals, the sensitivity of vessels in all LP
      fractions (LDL, VLDL and HDL (low, very low and high density LP)) was lower as a
      result of age changes in the reactivity of vessels. The capacity of HDL to
      produce a vasodilatory effect decrease with age, which may be linked to changes
      in the lipid and apolipoprotein composition. The results revealed a decrease in
      the level of phospholipids and an increase in the amount of total cholesterol in
      HDL observed in old age. The capacities of LDL and VLDL to exert a vascular
      dilatatory action remained unchanged with age.

PMID- 9234236
TI  - Rapid decrease of glycogen concentration in the hearts of senescence-accelerated
      mice during aging.
AB  - Age-related changes in glycogen concentration in the heart of SAMP8, a substrain
      of senescence-accelerated prone mouse, were compared with that in SAMR1, a
      substrain of senescence-accelerated resistant mouse. The decrease by about 50% in
      the glycogen concentration in the hearts of 4-8 weeks old SAMP8 was observed in
      comparison with that in age-matched SAMR1, whereas there was no difference in
      adult hearts between the two substrains. Additionally, glycogen phosphorylase
      activity was significantly increased (1.3-fold) in the heart of 4-8 weeks old
      SAMP8 without the change in glycogen synthase activity between the two
      substrains. At the same age, the lipid peroxide concentration was also increased
      (1.4-fold) in the hearts of SAMP8, suggesting that oxidative stress was involved
      in the early damage to the hearts of SAMP8. Furthermore, the present findings
      that the cardiac glycogen concentration in SAMP8 decreases more quickly than that
      in SAMR1 may indicate the possibility that an accelerated aging of SAMP8 is
      related to the early changes in the energy sources in the heart.

PMID- 9234235
TI  - Aging and detoxifying enzymes responses to hypoxic or hyperoxic treatment.
AB  - We studied the levels of antioxidant and detoxifying enzymes in the livers and
      lungs of young and old rats kept under hypoxic or hyperoxic conditions as models
      of oxidative stress. In particular, we investigated the levels of enzymes
      directly involved in active oxygen species scavenging (superoxide dismutase,
      catalase and glutathione peroxidase-selenium dependent) and enzymes challenged
      with detoxification processes (glutathione transferase, glyoxalase I and
      glutathione reductase) in order to obtain a wide comparative view of the defence
      strategies used with respect to the age of the animals. The results show that the
      responses of some protective enzymes in young rats are opposite to those of old
      ones. Some of the changes found appear mainly due to age, while others appear to
      be due only to the oxygen tensions and are independent of the aging process. The
      glutathione contents of the liver and lung from young and old rats under hypoxic
      and hyperoxic conditions were measured.

PMID- 9234237
TI  - Effect of age on the activity of phosphoenolpyruvate carboxykinase in the kidney
      following fasting and refeeding.
AB  - The activity of renal phosphoenolpyruvate carboxykinase (PEPCK) was measured in 3
      18 month old male Fischer 344 rats after alternate periods of fasting and
      refeeding. To compare the induction of renal PEPCK activity in response to
      fasting in young and old rats, 3, 6, 12 and 18 month old animals were fasted for
      30 h followed by a 24 h ad libitum refeeding period to reduce PEPCK activity
      toward basal levels. The refeeding period was followed by a second 24 h fasting
      period during which the time course of PEPCK induction was monitored in the young
      and old animals. The first fast resulted in over a 20% increase in renal PEPCK
      activity in the 3 month old and slightly over a 70% increase in the 6 month old
      animals. In contrast, the activity did not increase significantly in the 12 or 18
      month old animals during this fasting period. Therefore the induction of PEPCK in
      the kidney in response to fasting appears to be altered in the older animals.
      Refeeding for 24 h resulted in a decrease in PEPCK activity in all four age
      groups; therefore there was no indication of an age-related impairment in the
      response of renal PEPCK to refeeding. After the refeeding period, the food was
      removed again and the activity was measured at short intervals over the next 24 h
      to determine the time course of the induction in PEPCK activity. Interestingly,
      during the second fast, the activity of renal PEPCK was not significantly induced
      in either the young or the older animals. However, the activity measured in the
      older 18 month rats was consistently lower during the first 12 h of the second
      fast as compared to the activity in the 6 month old rats. In summary, the
      induction of PEPCK activity in the kidney is altered with age during an initial
      fast; in addition, PEPCK activity is not induced in either young or old rats
      during a second fasting period.

PMID- 9234238
TI  - Expression of mRNAs of pancreatic and L type RNase inhibitors as a function of
      age in different tissues of SAMP8 and BDF1 mice.
AB  - Turnover of mRNAs could be influenced not only by the synthesis of different mRNA
      species but also by the altered levels of mRNA-degrading enzymes such as RNases
      and their endogenous inhibitors. In the present work we evaluated possible age
      related changes in the mRNA levels of pancreatic as well as L type RNase
      inhibitors in five different tissues of the BDF1, SAMR1 and SAMP8 using Northern
      blots. The mRNA levels varied depending on the tissues and mouse strains studied.
      In certain instances such as the RNase L inhibitor mRNA levels in the lung of
      SAMP8, there was a statistically significant (P < 0.05) increase of 40% if we
      compared the young (3 months old) and old (18 months old) animals. These changes
      could possibly contribute to a certain extent to the already lower levels of
      mRNAs due to decreased transcriptional activities in aged animals.

PMID- 9234239
TI  - The Skirball Institute of Biomolecular Medicine: an infant among giants.

PMID- 9234240
TI  - The Werner mutation: does it lead to a "public" or "private" mechanism of aging?

PMID- 9234241
TI  - Priming of cytotoxic T lymphocytes by DNA vaccines: requirement for professional
      antigen presenting cells and evidence for antigen transfer from myocytes.
AB  - BACKGROUND: MHC class I molecule-restricted cytotoxic T-lymphocyte (CTL)
      responses are induced following either intramuscular (i.m.) injection of a DNA
      plasmid encoding influenza virus nucleoprotein (NP) or transplantation of
      myoblasts stably transfected with the NP gene, the latter indicating that
      synthesis of NP by myocytes in vivo is sufficient to induce CTL. The present
      study was designed to investigate the role of muscle cells and involvement of
      professional antigen-presenting cells (APCs) in priming CTL responses following
      DNA vaccination. MATERIALS AND METHODS: Parent-->F1 bone marrow (BM) chimeric
      mice were generated whose somatic cells include muscle cells bearing both
      parental MHC haplotypes, while their professional APCs express only the donor MHC
      haplotypes. RESULTS AND CONCLUSIONS: Upon injection of NP DNA, or after infection
      with influenza virus, CTL responses generated in the chimeras were restricted to
      the donor MHC haplotype. Thus cells of BM lineage were definitively shown to be
      responsible for priming such CTL responses after infection or DNA immunization.
      Moreover, expression of antigen by muscle cells in BM chimeric mice after
      myoblast transplantation is sufficient to induce CTL restricted only by the MHC
      haplotype of the donor BM. This indicates that transfer of antigen from myocytes
      to professional APCs can occur, thus obviating a requirement for direct
      transfection of BM-derived cells.

PMID- 9234242
TI  - The role of a single formin isoform in the limb and renal phenotypes of limb
      deformity.
AB  - BACKGROUND: Mutations of the murine limb deformity (ld) locus are responsible for
      a pleiotropic phenotype of completely penetrant limb malformations and
      incompletely penetrant renal agenesis and/or dysgenesis. The ld locus encodes a
      complex family of mRNA and protein isoforms. MATERIALS AND METHODS: To examine
      the role of one of the more prominent of these isoforms, isoform IV, we
      specifically eliminated it by gene targeting. RESULTS: Unlike other mutant ld
      mice, homozygous mice bearing this isoform IV disruption display incompletely
      penetrant renal agenesis, but have perfectly normal limbs. Whole mount in situ
      hybridization demonstrated that this targeted disruption was specific for isoform
      IV and did not interfere with the expression of other ld isoforms. The isoform IV
      disrupted allele of ld does not complement the renal agenesis phenotype of other
      ld alleles, in a manner consistent with its penetrance, and like the isoform IV
      deficient mice, these compound heterozygotes have normal limbs. Sequence analysis
      of formin isoform IV in other ld mutant alleles did not detect any amino acid
      changes relative to the strain of origin of the mutant allele. CONCLUSIONS: Thus,
      the disruption of isoform IV is sufficient for the renal agenesis phenotype, but
      not the limb phenotype of ld mutant mice. Structural mutations in this isoform
      are only one of several genetic mechanisms leading to the renal phenotype, since
      amino acid changes in this isoform were not detected. These results demonstrate
      that this gene is limb deformity, and that variable isoform expression may play a
      role in generating the pleiotropic ld phenotype.

PMID- 9234243
TI  - Degradation of C1-inhibitor by plasmin: implications for the control of
      inflammatory processes.
AB  - BACKGROUND: A correct balance between protease and inhibitor activity is critical
      in the maintenance of homoeostasis; excessive activation of enzyme pathways is
      frequently associated with inflammatory disorders. Plasmin is an enzyme
      ubiquitously activated in inflammatory disorder, and C1-inhibitor (C1-Inh) is a
      pivotal inhibitor of protease activity, which is particularly important in the
      regulation of enzyme cascades generated in plasma. The nature of the interaction
      between plasmin and C1-Inh is poorly understood. MATERIALS AND METHODS: C1-Inh
      was immunoadsorbed from the plasma of normal individuals (n = 21), from that of
      patients with systemic lupus erythematosus (n = 18) or adult respiratory distress
      syndrome (n = 9), and from the plasma and synovial fluid of patients with
      rheumatoid arthritis (n = 18). As plasmin is a putative enzyme responsible for C1
      Inh was examined using SDS-PAGE. In addition, peptides cleaved from C1-Inh by
      plasmin were isolated and sequenced and the precise cleavage sites determined
      from the known primary sequence of C1-Inh. Homology models of C1-Inh were then
      constructed. RESULTS: Increased levels of cleaved and inactivated C1-Inh were
      found in each of the inflammatory disorders examined. Through SDS-PAGE analysis
      it was shown that plasmin rapidly degraded C1-Inh in vitro. The pattern of C1-Inh
      cleavage seen in vivo in patients with inflammatory disorders and that produced
      in vitro following incubation with plasmin were very similar. Homology models of
      C1-Inh indicate that the majority of the plasmin cleavage sites are adjacent to
      the reactive site of the inhibitor. CONCLUSIONS: This study suggests that local
      C1-Inh degradation by plasmin may be a central and critical event in the loss of
      protease inhibition during inflammation. These findings have important
      implications for our understanding of pathogenic mechanisms in inflammation and
      for the development of more effectively targeted therapeutic regimes. These
      findings may also explain the efficacy of anti-plasmin agents in the treatment of
      C1-Inh deficiency states, as they may diminish plasmin-mediated C1-Inh
      degradation.

PMID- 9234244
TI  - HLA-H and associated proteins in patients with hemochromatosis.
AB  - BACKGROUND: The 845A(C282Y) mutation in the HLA-H gene accounts for most cases of
      hereditary hemochromatosis in patients who are of European origin. Some lack this
      mutation, however, and it is not present in Asian patients. Thus, other mutations
      either in HLA-H or associated proteins may be present in such patients. HLA-H
      associates with beta-2-microglobulin. Calreticulin associates with class 1 HLA
      proteins and appears to be identical with mobilferrin, a putative iron transport
      protein. These two proteins are therefore candidates for mutations in patients
      with hemochromatosis. MATERIALS AND METHODS: We have sequenced the coding region
      and parts of introns of the HLA-H gene, the beta-2-microglobulin gene, and the
      calreticulin (mobilferrin) gene of 10, 7, and 5 hemochromatosis patients,
      respectively, selecting those who were not homozygous for the 845A(C282Y)
      mutation. The number of chromosomes at risk studied were 18 for HLA-H, 14 for
      beta-2-microglobulin and 10 for calreticulin. RESULTS: We detected 3 new intronic
      polymorphisms in the HLA-H gene, each a point mutation. Some differences from
      published sequences of beta-2-microglobulin and calreticulin were documented, but
      these were uniformly present in all samples. CONCLUSIONS: The lack of additional
      mutations in the HLA-H gene is remarkable, and we speculate that the C282Y
      mutation may be a gain-of-function change.

PMID- 9234245
TI  - Cystic fibrosis of the pancreas: involvement of MUC6 mucin in obstruction of
      pancreatic ducts.
AB  - BACKGROUND: Cystic fibrosis (CF) is characterized by pancreatic destruction
      following the gradual obstruction of small pancreatic ducts, from the mid
      trimester of gestation onwards. To date, the material causing the obstruction has
      not been identified. The MUC6 mucin cDNA was isolated from human stomach and has
      been shown to be expressed in a number of other tissues in the gastrointestinal
      tract, including the gall bladder and parts of the ileum and colon. MATERIALS AND
      METHODS: We have examined the expression of MUC6 mucin in the human pancreas,
      both during development and postnatally, by mRNA in situ hybridization and
      immunocytochemistry. RESULTS: In this report we establish that MUC6 transcripts
      are abundant in pancreatic epithelial cells and show a very similar pattern of
      expression in the epithelium lining small ducts and centroacinar cells to that
      shown by the cystic fibrosis transmembrane conductance regulator gene (CFTR). In
      addition, material obstructing the pancreatic ducts of CF pancreas was shown to
      contain MUC6 mucin. CONCLUSION: We have identified MUC6 mucin as a significant
      constituent of the material obstructing the small pancreatic ducts in CF.

PMID- 9234246
TI  - [Classification and clinical topics on familial spinocerebellar degeneration].

PMID- 9234247
TI  - [On the conception of the brainstem death].

PMID- 9234248
TI  - [Protective effect of L-histidine (singlet oxygen scavenger) on transient
      forebrain ischemia in the rat].
AB  - Histidine is an efficient scavenger of highly active singlet oxygen and somewhat
      weaker scavenger of hydroxyl radicals. And it has been shown to protect against
      reperfusion injury in the heart. The effects of L-histidine were examined in the
      forebrain ischemia reperfusion injury of the rat hippocampus (CA-1). Male Wistar
      rats were treated with the free radical scavenger L-histidine for 30 minutes
      before transient forebrain ischemia produced by 4-vessel occlusion. The
      extracellular concentrations of glutamate were measured by cerebral
      microdialysis. The intravenous (i.v.) administration of 50 mg/kg and 100 mg/kg L
      histidine protected the elevation of extracellular glutamate concentrations after
      transient cerebral ischemia (p < 0.01). And the administration of L-histidine
      prevented ischemia-reperfusion induced delayed neuronal death in the rats.
      Morphological changes in the CA-1 sector of the hippocampus were evaluated 7 days
      after 10 minutes occlusion. The average neuronal density of treated groups showed
      a statistically significant (p < 0.01) persistence compared with that of control
      groups. These results indicate that L-histidine can reduce neuronal damage after
      reperfusion of cerebral ischemia and further suggest that excitatory amino acid
      and oxygen free radicals may damage the brain by a common pathway.

PMID- 9234249
TI  - [The EMG findings of spasmodic torticollis--the character of the EMG findings of
      neurogenic torticollis].
AB  - Spasmodic torticollis is a clinical entity that is hard to treat though various
      symptomatic therapy have been tried. On the other hand, microvascular
      decompression operation have been established for cranial nerve vascular
      compression syndrome such as hemifacial spasm. Case reports on the decompression
      of the spinal accessory nerve for the treatment of spasmodic torticollis have
      been published on the basis of the concept of cranial nerve vascular compression
      syndrome. Thus, spasmodic torticollis related to unilateral accessory nerve has
      attracted much attention for selecting an optimal treatment, although there have
      not been any diagnostic criteria with electromyographic study. From the viewpoint
      of the clinical electrophysiological findings on hemifacial spasm those we have
      acquired by EMG study, we have examined the EMG findings of various types of
      spasmodic torticollis and here report the classification of spasmodic torticollis
      based on the EMG study. Thirty-five patients with spasmodic torticollis were
      analyzed. The symptoms were classified to the horizontal rotation type, the
      lateral bending type and the mixed type with the number of each group of 23, 2
      and 10, respectively. As we have shown the criteria of the EMG findings on
      hemifacial spasm, the EMG of the patients with spasmodic torticollis were
      analyzed on four conditions as follows; (1) distribution of the involved muscles,
      (2) maximum firing rate of the abnormal spontaneous activity of the
      sternocleidomastoid muscle, (3) synkinetic discharge between the muscles
      innervated by unilateral accessory nerve and (4) alteration of the spontaneous
      muscle discharge by posture change. Abnormal spontaneous muscle discharges were
      recorded only from the sternocleidomastoid muscle and the trapezius muscle on the
      same side in twelve patients. Maximum firing rate of spontaneous muscle discharge
      was higher than that of maximum voluntary contraction in twenty-two patients.
      Abnormal synkinetic discharge was recorded between the sternocleidomastoid muscle
      and the trapezius muscle on the same side in twenty-one patients. Spontaneous EMG
      activities of the muscles innervated by the accessory nerve increased when the
      patients stood up from the resting supine position in thirty-one patients. Thus,
      ten patients out of thirty-five subjects had all four conditions mentioned above
      as typical patients with hemifacial spasm usually had. These ten patients with
      spasmodic torticollis were thought to have strong similarity to the EMG
      characteristics of hemifacial spasm that suggested hyperexcitability of
      unilateral accessory nervous system. This classification with EMG is considered
      to be useful in diagnosing the spasmodic torticollis related to unilateral
      accessory nerve and can be applied for selecting an optimal treatment.

PMID- 9234250
TI  - [Gait disturbance without motor and sensory involvement in cervical myelopathy-
      clinical course and radiological findings].
AB  - Among 100 patients with cervical myelopathy, we found 7 patients with gait
      disturbance in which motor or sensory involvements were absent (group A). In
      these patients, the gait was unsteady, but not ataxic nor spastic. Some of them
      showed mild hyperreflexia, but no one had Romberg's sign. We compared the effect
      of neck traction and radiological findings in group A with these in 25 patients
      who had gait disorders as well as other symptoms associated with cervical
      myelopathy (group B). Mean age in group A (mean 83.9 +/- 7.9 ys) was older than
      that in group B (mean 76.6 +/- 5.7 ys). Gait disorders improved in 6 cases of
      group A (86%), and 5 cases in group B (20%) by conservative therapy of Glisson's
      traction. On plain X-ray examination, the physiologic lordosis of cervical spine
      was preserved, the cervical canal diameters from C2 to C7 were more wide, and the
      number of intervertebral excessive mobility had tendency to be less in group A
      than in group B. Cervical MRI indicated that the number of intervertebral spinal
      compression was less in group A than in group B. In the cervical myelopathy,
      there was a type showing only gait disturbance which was characterized by the
      good response to Glisson's neck traction, and by the preserved physiological
      lordosis, relatively wide spinal canal, and slight intervertebral compression.

PMID- 9234252
TI  - [White matter lesions after occlusion of the bilateral carotid arteries in the
      rat--temporal profile of cerebral blood flow (CBF), oligodendroglia and myelin].
AB  - In the present investigation, we examined cerebral blood flow (CBF), numerical
      density of oligodendroglia and extent of white matter lesions after bilateral
      ligation of common carotid arteries in Wistar rats. Doppler flow-meter revealed a
      reduction of CBF to 30-40% of that before operation after 1 and 3 days, however
      recovered to 50-60% after 7 and 14 days. Semiquantitative evaluation with
      immunohistochemistry for transferrin showed a numerical decrease of
      oligodendroglia in the medial corpus callosum after 14 and 30 days. Tissue rare
      faction promptly occurred in the optic nerve and optic tract after 3 days,
      whereas it was delayed to 7 days after operation and increased in intensity
      gradually in the other white matter regions. These results indicate that
      bilateral occlusion of common carotid arteries in Wistar rats elicits a chronic
      cerebral hypoperfusion, which cumulatively leads to delayed appearance of white
      matter lesions.

PMID- 9234251
TI  - [Angiographical evaluation of extracranial carotid artery: comparison between
      Japanese and Hungarian].
AB  - We investigated the cervical level of carotid bifurcation, diameter of common
      carotid artery (CCA) and internal carotid artery (ICA) in 147 Japanese patients
      (150 arteries, range of age 31-79) and in 490 Hungarian patients (517 arteries,
      range of age 12-77). The cervical level of carotid bifurcation was determined by
      comparison with cervical vertebra. The carotid bifurcation of Japanese was most
      frequent at the lower part of 3rd cervical vertebra but in Hungarian the
      bifurcation was most frequent at the middle part of 4th cervical vertebra.
      Japanese carotid bifurcation was high-positioned compared with Hungarian. The
      mean CCA diameter in Japanese was 7.47 mm in male and 7.07 mm in female, in
      Hungarian 9.24 mm in male and 7.80 mm in female. The mean ICA diameter in
      Japanese was 4.96 mm in male and 4.83 mm in female, in Hungarian 8.56 mm in male
      and 7.66 mm in female. CCA and ICA diameter were larger in male than in female.
      The diameter of CCA had a significantly positive correlation with age (p < 0.002)
      but ICA had no similar correlation.

PMID- 9234253
TI  - [Progressive loss of speech output with festinating speech--a case report].
AB  - Primary progressive aphasia is a rare disorder of unknown cause. We report a
      patient with progressive loss of speech output, a clinical variant of PPA,
      characterized by festinating speech. A 60-year-old right handed woman was
      admitted to our hospital, because of progressive deterioration of her speech. On
      admission, she was alert and orientated without dementia. A severe impairment of
      her articulation was observed: her speech rate was so fast that her speech became
      almost intelligible. The orofacial apraxia and difficulty in tapping were also
      present. The other neurological findings were normal. Neuroradiological studies
      showed the left perisylvian atrophy. Festinating speech has not been previously
      reported in patients with PPA; patient with PPA usually show a slow speech rate
      with effortful expression. Since festinating speech is occasionally present in
      the extrapyramidal disorders, such as Parkinson's disease, progressive
      supranuclear palsy, or pure akinesia, it appears likely that the combined lesions
      of the perisylvian region and the basal ganglia are responsible for her
      characteristic speech disorder with festinating speech.

PMID- 9234254
TI  - [Steroid responsive chronic brainstem encephalitis featuring mental symptoms,
      abnormal eye movement and cerebellar ataxia].
AB  - A 53-year-old man presented with progressive ataxia two and a half years prior to
      admission. Initially he was treated in a local hospital for 4 months with a
      diagnosis of spinocerebellar degeneration. Subsequently he developed psychomotor
      excitement with hallucination and was admitted to a mental hospital for 7 months
      with a diagnosis of Wernicke's encephalopathy. After a year of partial remission,
      he presented with increasing difficulty in thinking and walking. On admission he
      developed mental agitation and excitement, ocular flutter and opsoclonus, and
      prominent cerebellar ataxia. A lymphocytic pleocytosis in the CSF and a high
      intensity lesion in the superior cerebellar peduncle of the upper brainstem
      revealed on a T2-weighted MRI led to a diagnosis of brainstem encephalitis.
      Treatment with steroid (two series of 3 days of 1,000mg methylprednisolone DIV,
      followed by 60mg oral prednisolone) brought about a dramatic improvement in
      mental and ocular symptoms corresponding with the CSF findings. He was left with
      mild cerebellar ataxia and returned to work on a small dose of steroids.
      Differential diagnoses including Bickerstaff's encephalitis and pathomechanism
      were discussed.

PMID- 9234255
TI  - [An autopsy case of multiple myeloma with pineal body and spinal cord dura mater
      infiltration].
AB  - An autopsy case of multiple myeloma (IgD lambda type) with pineal body and spinal
      cord dura mater infiltration is reported. The 63-year-old man was diagnosed as
      multiple myeloma (IgD lambda type). He was treated with melphalan and
      prednisolone. Extra bone marrow masses developed 1 year after the onset. He died
      with renal failure. At autopsy there were many extra bone marrow masses including
      pineal body and dura mater of the thoracic cord. Microscopic examination revealed
      that those mass lesions consisted of neoplastic plasma cells. Myeloma cells also
      infiltrated perivascular space near the pineal body, subdural space of the
      cerebrum and brain stem. The cells were labeled VS 38 c immunohistochemically. We
      discussed routes of the metastasis to the central nervous system of the multiple
      myeloma. This case suggests that the way of myeloma cells infiltration to the
      pineal body is hematogenous metastasis, because pineal body have no blood brain
      barrier.

PMID- 9234256
TI  - [Epidural granuloma following craniotomy].

PMID- 9234257
TI  - [(Neurological CPC.55). A 60-year-old woman with progressive cerebellar ataxia,
      myoclonus, and dementia].
AB  - We report a 60-year-old woman with progressive ataxia, myoclonus,
      choreoathetosis, and dementia. She was well until 27 years of the age when she
      noted an onset of gait disturbance and speech disturbance. She noted abnormal
      involuntary movements in her four limbs at 42 years of the age. Her symptoms had
      progressively become worse and she fell down frequently by her 52 years of the
      age. In addition, her family members noted gradual decline in her intelligence.
      She was admitted to our hospital in February of 1993 when she was 57-year-old. On
      admission, she showed dementia, scanning speech, ataxic gait, limb ataxia, action
      myoclonus, and choreic movements which involved her four limbs. Deep tendon
      reflexes were slightly exaggerated in the lower limbs; no Babinski sign was
      noted. Sensation was intact. Laboratory findings were unremarkable. Cerebral MRI
      revealed atrophy of the cerebellar cortex, superior cerebellar peduncle, brain
      stem, and the cerebral cortex; the third ventricle and the lateral ventricles
      were dilated; furthermore, T2-high signal lesions were seen in the cerebral white
      matter and in the pontine base. Her clinical course was one of the progressive
      deterioration of her ataxia, involuntary movements, and dementia. She expired on
      April 24, 1996 when she was 60-year-old. She was discussed in a neurologic CPC
      and the chief discussant arrived at the conclusion that the patient had
      dentatorubral-pallidoluysian atrophy. A minor opinion was that she might have had
      myoclonus epilepsy with ragged-red fibers. Postmortem examination revealed
      atrophy, gliosis, and neuronal loss in the external segment of the globus
      pallidus, subthalamic nucleus, red nucleus, and in the dentate nucleus. In
      addition, the gracil and cuneiform nuclei showed neuronal loss and spheroid
      formation; the spinocerebellar tracts were retained. The substantia nigra and the
      locus coeruleus were intact. No ragged-red fibers were seen in the muscle biopsy
      specimen taken in February, 1993. The neuropathologic findings were consistent
      with the diagnosis of dentatorubral-pallidoluysian atrophy.

PMID- 9234258
TI  - The International Chernobyl Project Technical Report: assessment of radiological
      consequences and evaluation of protective measures. Report by an International
      Advisory Committee.

PMID- 9234260
TI  - Decreased kidney uptake of technetium-99m-labelled Fab' fragments in ovarian
      carcinoma bearing nude mice using a cleavable chelator.
AB  - A new 99mTc labelling method using a cleavable chelator, RP-1, was developed. In
      this study Balb/c mice with ovarian carcinoma xenografts received various Fab'
      fragments labelled with 99mTc either directly or via RP-1. Kidney uptake was
      significantly lower for the RP-1 linked conjugates. Tumour uptake showed no
      significant differences between RP-1 conjugates and directly labelled
      preparations. In conclusion, with the use of the cleavable linker RP-1, kidney
      uptake can be reduced significantly resulting in a lower radiation dose to the
      kidneys.

PMID- 9234259
TI  - Clinical comparison of radiolocalization of two monoclonal antibodies (mAbs)
      against the TAG-72 antigen.
AB  - Ten patients with colorectal cancer metastases received 125I-B72.3 and 131I-CC49
      prior to laparotomy (five patients received 1 mg, and five 20 mg of each mAb).
      Tumor:serum ratios of 131I-CC49 were better than those of 125I-B72.3 (P < 0.01 at
      1 mg; P = 0.05 at 20 mg; P < 0.01 at both doses). All known lesions > or = 1 cm
      in diameter were visualized at the 20 mg dose. There was no difference in
      absolute tumor uptake of 125I-B72.3 or 131I-CC49. We conclude that mAb CC49 has
      better relative uptake in colorectal cancers than mAb B72.3.

PMID- 9234261
TI  - Oxohexestrol derivatives labeled with fluorine-18. Synthesis, receptor binding
      and in vivo distribution of two non-steroidal estrogens as potential breast tumor
      imaging agents.
AB  - We have prepared two non-steroidal estrogens in the 2-oxohexestrol series labeled
      with the positron-emitting radionuclide fluorine-18, 1-fluoro-5-oxohexestrol (4)
      and 1-fluoro-2-oxohexesterol (5). We anticipated that the polar ketone function
      at the interior of these ligands would reduce their level of non-specific
      binding, which might increase the selectivity of their uptake in vivo. The two
      compounds were prepared by total synthesis: compound 4 was prepared in fluorine
      18 labeled form by [18F]fluorine ion displacement on a suitably protected
      methanesulfonate precursor followed by deprotection under acidic hydrogenolytic
      conditions; the isomer 5 was prepared from a protected alpha-keto
      trifluoromethanesulfonate precursor with deprotection under basic conditions as
      the final step. The binding affinity of these hexestrol derivatives for the
      estrogen receptor was determined by competitive radiometric binding assays at 0
      and 25 degrees C, and their lipophilicity (as octanol-water partition
      coefficients, log P values) and non-specific binding were estimated. The log P
      values determined by a reversed phase HPLC method were higher, relative to
      estradiol, than those calculated by the fragment method of Rekker. In tissue
      distribution studies in immature (50 g) rats, both of these compounds showed
      selective uptake in estrogen target tissues. At 1 h, activity in the uterus
      reached the level of 2.5-3.0% of the injected dose per gram tissue, with uterus
      to-blood and uterus-to-muscle ratios of 14-20 and 8-14, respectively. The uptake
      efficiency and selectivity of these fluoro-oxohexestrols in principal estrogen
      target tissues is less than that of fluorine-18 labeled steroidal estrogens we
      have prepared previously, but their receptor-mediated uptake in certain secondary
      target tissues is substantial. The specific and non-specific components of target
      tissue uptake of these two compounds appear to be directly related to their non
      specific binding and their binding selectivity.

PMID- 9234262
TI  - Rodent biodistribution and metabolism of tritiated 4-DAMP, a M3 subtype-selective
      cholinoceptor ligand.
AB  - The biodistribution of [3H]4-DAMP (a M3-selective cholinoceptor antagonist) was
      studied in rats which had received either saline or saline containing atropine
      (to block cholinoceptors). Specific binding of the radioligand was observed in
      the urinary bladder, ileum, pancreas, stomach, submandibular gland and trachea.
      Maximal ratios of total-to-non-specific uptake reached values of 1.8 (trachea),
      3.2 (bladder), 4.0 (stomach), 4.8 (ileum), 6.6 (pancreas) and 6.9 (submandibular
      gland) at 5-10 min post-injection; this rank order reflects the tissue densities
      of M3 cholinoceptors, 4-DAMP did not bind to blood cells and it was rapidly
      cleared from the circulation (> 90% with a half-life of 0.2 min, the remainder
      with a half-life of 9.4 min). Labelled metabolites appeared within 5 min in
      plasma, but metabolite uptake by the target organs was low (< 15% of total
      radioactivity 40 min post-injection). Although 4-DAMP binds to M3-cholinoceptors
      in vivo, its potential use as a radiopharmaceutical appears limited since the
      compound does not cross the blood-brain barrier and it does not show measurable
      specific binding in airways.

PMID- 9234263
TI  - Preparation and pharmacological characterization of [76Br]-meta
      bromobenzylguanidine ([76Br]MBBG).
AB  - [76Br]-meta-Bromobenzylguanidine ([76Br]MBBG) was prepared from the iodinated
      analog (MIBG) and [76Br]NH4 using a Cu(+)-assisted halogen exchange reaction.
      [76Br]MBBG was produced in a 60-65% radiochemical yield with a specific activity
      of 20 MBq/nmol. In rats, biodistribution kinetic studies showed a high uptake of
      [76Br]MBBG in heart tissues with its maximum of 5% ID/S at 2 h p.i.; whereas 4 h
      p.i., the maximum of the heart-to-lung concentration ratio of 8 was observed.
      Metabolic studies in rats indicated that [76Br]MBBG was rapidly metabolized in
      plasma. However in heart tissue, 25 h p.i., 85% of the radioactivity still
      represented unchanged radiotracer. Pharmacological studies in rats showed that
      the myocardial uptake of [76Br]MBBG was similar to that of norepinephrine. After
      pretreatment of the rats, the uptake of [76Br]MBBG was reduced 4 h p.i. to the
      following values: after desipramine (DMI) to 37%, after dexamethasone (DXM) to
      88% and after 6-hydroxydopamine (6-OHDA) to 16%. These preliminary results
      suggest that [76Br]MBBG can be useful for the assessment of heart catecholamine
      reuptake disorders with PET.

PMID- 9234264
TI  - Radioiodinated nordiazepam analog for in vivo assessment of benzodiazepine
      receptors by single photon emission tomography.
AB  - 2'-Iodo-nordiazepam (2'-IND), a nordiazepam analog iodinated at the 2'-position
      of the C-5 phenyl ring, was synthesized and evaluated as a potential
      radiopharmaceutical for investigating brain benzodiazepine receptors by SPECT.
      [125I]2'-IND was synthesized by the halogen exchange reaction and purified by
      HPLC. In an in vitro competitive binding study using [3H]diazepam and rat
      cortical synaptosomol membranes, 2'-IND showed an almost equal affinity for
      benzodiazepine receptors as diazepam. In a saturation binding study using rat
      cortical synaptosomal membranes, 2'-IND displayed a Kd of 1.10 nM and a Bmax of
      1.87 pmol/mg protein. Biodistribution and metabolism studies in mice showed that
      [125I]2'-IND exhibited rapid and high accumulation in the brain, and that the
      cerebral uptake and distribution of this compound occurred in the intact form.
      Furthermore, the administration of diazepam and flumazenil reduced cortical
      uptake by approx. 20%, suggesting that the uptake of 2'-IND occurred at least
      partly in association with benzodiazepine receptors.

PMID- 9234265
TI  - A newly designed radioimmunoconjugate releasing a hippurate-like radiometal
      chelate for enhanced target/non-target radioactivity.
AB  - Target-to-non-target ratio of radioactivity can be enhanced by the injection of
      monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some
      modality to accelerate the urinary excretion of radioactivity accumulated in non
      target tissues could be introduced. In this study, a radioimmunoconjugate
      chemically designed to release a hippurate-like radiometal chelate was
      synthesized and tested in vivo. A 67Ga chelate of succinyldeferoxamine (SDF) was
      conjugated with a MoAb against osteogenic sarcoma (OST7, IgG1) through an ester
      bond using a new metabolizable MESS linker, N-[I4
      (maleimidoethoxy)succinyl]oxy]succinimide (67Ga-DFO-MESS-OST7). When injected
      into normal mice, 67Ga-DFO-MESS-OST7 exhibited faster clearance of radioactivity
      from circulation with less accumulation in the liver, kidney and spleen than
      those observed with 67Ga-DFO-EMCS-OST7, which was prepared under identical
      conditions to 67Ga-DFO-MESS-OST7 except for using a non-metabolizable linker
      holding no ester bond to release 67Ga-SDF. Size exclusion HPLC analysis of the
      liver homogenate obtained from mice 24 h after injection of 67Ga-DFO-MESS-OST7
      indicated that all the radioactivity was eluted in the high molecular weight
      fraction with most of it being present as the 67Ga-DFO-MESS-OST7 fraction.
      Reverse-phase HPLC analysis of urine sample from the same mice showed a single
      radioactivity peak at the same retention time as that of 67Ga-SDF. In athymic
      mice bearing osteogenic sarcoma, 67Ga-DFO-MESS-OST7 exhibited higher tumor-to
      blood and tumor-to-organ ratio of radioactivity when compared with 67Ga-DFO-EMCS
      OST7. These results indicated that 67Ga-DFO-MESS-OST7 achieved enhanced target-to
      non-target ratio of the radioactivity, due to preferential cleavage of the ester
      bond in non-target tissues, followed by rapid urinary excretion of the resulting
      chelate (probably as 57Ga-SDF). These results also suggest that the present
      design would become an applicable modality for enhancing the target-to-non-target
      ratio of radioactivity by MoAbs.

PMID- 9234266
TI  - Tumor detection by radioimaging of hepatic radiozinc--correlation with
      metallothionein content.
AB  - In order to determine if the radioimaging of the level of hepatic metallothionein
      (MT) is able to detect malignancy, we performed, using 45Zn, a trial to measure
      MT levels in the liver of experimental tumor-bearing mice and rats. The
      distribution of 65Zn in the livers of the mice and rats increased with s.c.
      transplantation of Ehrlich carcinoma and ascites hepatoma 7974F, respectively. A
      Sephadex G-75 elution profile of the cytosol fraction of the liver showed that
      the elevation of 65Zn level was due to elevation of the MT level. At 2 days after
      tumor transplantation in mice, the 65Zn-image demonstrated elevation of the
      hepatic MT level, while 67Ga-citrate, which is currently utilized, could not
      image the tumor at such an early period of growth. These results suggest that
      hepatic MT is a useful marker for the detection of malignancy at the early stage.

PMID- 9234267
TI  - Positron emission tomography study of human prostatic adenocarcinoma using carbon
      11 putrescine.
AB  - To evaluate [1-11C]putrescine ([11C]PUT) as a potential tracer for imaging and
      characterization of human prostatic adenocarcinoma, positron emission tomography
      (PET) was performed in eight patients and three normal controls. In addition,
      four of the patients and the three normal controls also had a prostate scan with
      2-deoxy-2-[18F]fluoro-D-glucose (18FDG). Three of the patients had undergone
      resection of the prostate tumor and all of the patients except for one had bone
      metastasis. Carbon-11 rapidly accumulated in prostate, bone and rectum after
      injection of [11C]PUT. Maximal uptake was achieved 5 min after injection with
      minimal washout during the 50 min study period. The uptake of carbon-11 in the
      prostate of normal controls was significantly higher than that in the patients.
      However, three of the four patients scanned for metastatic bone lesions showed
      higher uptake in bone metastasis than in normal bone. Quantitation of 18FDG
      uptake in the prostate was hindered by the high accumulation of activity in the
      urinary bladder. [11C]PUT does not appear to be a useful tracer for assessing
      proliferation of human prostate adenocarcinoma. Its utility in the imaging of
      other cancers with high polyamine concentration remains to be investigated.

PMID- 9234269
TI  - 99mTc-labeling of lipid vesicles containing the lipophilic chelator PE-DTTA:
      effect of tin-to-chelate ratio, chelate content and surface polymer on labeling
      efficiency and biodistribution behavior.
AB  - When injected intravenously, lipid vesicles labeled with 99mTc by means of a
      lipophilic chelator dipalmitoylphosphatidylethanolamine
      diethylenetriaminetetraacetic acid (PE-DTTA) are rapidly accumulated by the
      mononuclear phagocytic system (MPS). By derivatizing the membrane surface with
      the lipid-polymer complex dipalmitoylphosphatidylethanolamine-monomethoxy
      polyethylene glycol 5000 (PE-MPEG), MPS uptake can be suppressed and loss of
      99mTc label from the lipid surface reduced depending upon both PE-DTTA and PE
      MPEG content. For vesicles containing 20% PE-DTTA, addition of PE-MPEG makes no
      difference to their rate of clearance from the circulation. However for vesicles
      containing 2% PE-DTTA, addition of more than 0.8% PE-MPEG increases circulation
      half-life, suppresses liver uptake and reduces renal clearance of the 99mTc
      label. The molar ratio of reducing agent (Sn) to chelator (PE-DTTA) is critical
      to efficient and reproducible labeling. For vesicles containing 2% PE-DTTA at a
      lipid concentration of 100 mM, a Sn/DTTA ratio of 0.35 gives close to optimal
      labeling. Variation in the Sn/DTTA ratio by a factor of two negatively impacts
      upon both labeling efficiency in vitro and circulation half-life in vivo.
      Potential uses for technetium-labeled lipid vesicles with extended circulation
      half-life are discussed.

PMID- 9234268
TI  - Evaluation of Cu-PTSM as a tracer of tumor perfusion: comparison with labeled
      microspheres in spontaneous canine neoplasms.
AB  - Copper-62-labeled Cu-PTSM is a promising generator-produced PET tracer for
      myocardial, cerebral and renal perfusion. To evaluate whether [62Cu]Cu-PTSM could
      also serve as a blood flow tracer in PET studies of tumor tissue, the tumor
      uptake of [62Cu]Cu-PTSM was examined in dogs with spontaneously-occurring soft
      tissue neoplasms. Copper-67-labeled Cu-PTSM was administered intravenously to
      four anesthetized dogs, followed c. 5 min later by a left ventricular injection
      of 85Sr-labeled microspheres (15 microns) to provide an independent measure of
      tumor perfusion. Forty-seven tumors (average weight = 2.5 +/- 3.7 g) were
      obtained and sectioned into 80 samples. The correlation of 67Cu-PTSM uptake with
      regional renal perfusion was also examined in data from 395 tissue samples
      ranging in flow from 0.02 to 9.39 mL min-1 g-1. Rates of tumor perfusion assessed
      with 85Sr-labeled microspheres ranged from 0.011 to 3.0 mL min-1 g-1. No
      correlation was found between tumor size and the rate of tumor perfusion.
      However, an excellent linear correlation exists between tumor perfusion
      calculated from [62Cu]Cu-PTSM data and tumor perfusion measured with 85Sr
      microspheres (r = 0.94 for 80 samples), suggesting that [62Cu]Cu-PTSM may be
      useful as a radiopharmaceutical for PET studies of tumor perfusion.

PMID- 9234270
TI  - Synthesis and preliminary evaluation of para- and meta
      [18F]fluorobenzylguanidine.
AB  - meta-[18F]Fluorobenzylguanidine ([18F]MFBG) and para-[18F]fluorobenzylguanidine
      ([18F]PFBG) were synthesized in three steps beginning with a fluoro for nitro
      exchange reaction on 3- and 4-nitrobenzonitrile, respectively. Overall
      radiochemical yields were 10-15% for [18F]MFBG and 50-55% for [18F]PFBG in a
      total synthesis time of 60 min. However, impurities interfered with the binding
      of the product to target cells. A new route was adopted for the synthesis of
      [18F]PFBG using 4-nitrilophenyl trimethylammonium trifluoromethanesulfonate
      (Q.S.) as the starting material. In addition to shortening the overall synthesis
      time by 10 min, this precursor also eliminated problems associated with the
      presence of small amounts of starting material in the preparation. In vitro
      binding of [18F]PFBG prepared by the Q.S. method to SK-N-SH, human neuroblastoma
      cells was 26.5 +/- 1.1%, compared to 16.9 +/- 1.6% when the nitro precursor was
      used. Selective uptake of both 18F-labeled isomers in the heart and adrenal was
      seen in mice. At 4 h, adrenal and heart uptake of [18F]PFBG prepared using Q.S.
      was 20.3 +/- 4.8 and 5.9 +/- 0.8% ID/g respectively, compared to 23.8 +/- 5.0 and
      10.5 +/- 1.7% ID/g for [18F]MFBG. Based on the 5-fold higher radiochemical yields
      obtained with [18F]PFBG, this isomer would appear to be the more practical
      choice; however, in vitro and in vivo results suggest that [18F]MFBG exhibits
      greater similarities to MIBG.

PMID- 9234271
TI  - Monoclonal antibody F(ab')2 fragment labeled with N-succinimidyl 2,4-dimethoxy-3
      halobenzoates: in vivo comparison of iodinated and astatinated fragments.
AB  - N-Succinimidyl 3-[211At]astato-2, 4-dimethoxybenzoate (SADMB) was prepared from a
      trialkylstannyl precursor in about 70-75% yield. With either trimethyl or tri-n
      butylstannyl precursor, no temporal effect was found in the astatodestannylation
      yield. However, the methyl analog gave slightly better yield which was found to
      be not statistically significant. A monoclonal antibody (MAb) fragment, Mel-14
      F(ab')2, could be labeled using SADMB in 28% coupling efficiency. The specific
      binding of this labeled fragment to tumor homogenates in vitro was 61.0 +/- 0.5%
      (62.8 +/- 0.9% for the 131I labeled fragment). Paired-label tissue distribution
      in normal mice showed similar uptake of 131I and 211 At in many tissues. However,
      by 14.5 h selectivity of spleen, lungs and stomach for Mel-14 F(ab')2 labeled
      with 211At compared to 131I was 4.1, 3.8 and 6.4, respectively.

PMID- 9234272
TI  - Imaging of focal sites of inflammation in rhesus monkeys with 99mTc-labeled human
      polyclonal IgG.
AB  - The biological behavior of human polyclonal immunoglobulin G (IgG) radiolabeled
      with 99mTc via a nicotinyl hydrazine derivative, was evaluated in Rhesus monkeys.
      99mTc-IgG and 111In-MACROSCINT DTPA-IgG were co-administered to Rhesus monkeys
      with focal sites of sterile inflammation and scintillation camera images were
      acquired at 6 and 19 h after injection. The biodistribution of the two antibody
      preparations were similar, however, small differences were detected: 99mTc-IgG >
      111In-IgG in spleen and lung; 99mTc-IgG in bone and skeletal muscle. A linear
      correlation of the tissue-to-blood ratios of 99mTc- and 111In-labeled IgG was
      observed at both times (r2 > 0.98). The slopes of the regression lines were not
      significantly different from unity: 6 h-0.982 +/- 0.018; 19 h 1.0334 +/- 0.0226.
      Also, at both 6 and 19 h after injection, the target-to-background ratios (T/B)
      for the sites of inflammation were remarkably similar for 111In and 99mTc. These
      studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl
      hydrazine modified intermediate is equivalent to 111In-MACROSCINT DTPA-IgG for
      imaging focal sites of inflammation in monkeys.

PMID- 9234273
TI  - Synthesis and biodistribution of a new 99mtechnetium fatty acid.
AB  - The synthesis and biodistribution is described for a new 99mTc-labeled fatty
      acid. The requisite diaminodithiol (N2S2) ligand, 9,10-bis[N-(2'-methyl-2'
      mercapto)propyl] aminooctadecanoic acid, was prepared in nine steps from ethyl
      oleate and characterized by fast atom bombardment mass spectrometry and elemental
      analysis of its nickell(II) complex. The radiolabeling procedure provided a
      liposoluble 99mTc-labeled complex (99mTc-11) which was administered intravenously
      to rats concomitantly with 15-(p-[125I]-iodophenyl) pentadecanoic acid (IPPA).
      The myocardial profile of 99mTc-11 was inferior to that of IPPA.

PMID- 9234274
TI  - Influence of a syngeneic anti-idiotypic antibody response to a mouse anti-tumour
      monoclonal antibody on biodistribution of its radiolabelled Fc-intact monovalent
      Fab/c fragment.
AB  - It has previously been shown that a syngeneic anti-idiotypic (anti-id) antibody
      response generated in Balb/c mice to the monoclonal antibody (Mab) NCRC-2 can
      cause its clearance from the circulation. However, there was a positive
      prolongation of the survival of the Fab fragment, which is monovalent but also
      lacks Fc. The present study was carried out to examine the effect against the
      Fab/c fragment of this Mab, since this is also monovalent but has intact Fc.
      There was accelerated clearance, rather than retention. This suggests that anti
      id responses prolong survival of fragments because they lack Fc, rather than only
      because of their monovalency. Such monovalent, Fc deficient fragments, are the
      type of human antibody fragments most easily obtained by genetic engineering
      techniques for clinical use. The present findings have implication for the
      effects of patients' immune responses on the biodistribution of such fragments.

PMID- 9234276
TI  - Accumulation of some small molecular weight complexes of 99mTc in experimental
      abscesses.
AB  - The purpose of the present investigation was to evaluate the feasibility of
      imaging inflammatory lesions with some small molecular weight complexes of 99mTc
      with renal excretion in comparison to 99mTc-dextran (D), 99mTc-HIG and 67Ga
      citrate. The biodistributions of pertechnetate (P), 99mTc-citrate (Cit), 
      gluconate (G), -glucoheptonate (GH), -DTPA, -glucose phosphate (GP), -D, -HIG and
      67Ga-Cit were determined in mice with turpentine-induced abscesses at 1, 3, 6 and
      24 h after i.v. injection of 15 MBq. % uptake/g tissues and abscess/muscle (A/M),
      blood (A/B), liver (A/L), intestine (A/J) and kidney (A/K) concentration ratios
      were calculated. The scintigraphic images of all mice were obtained by a 7
      camera. The abscesses were well visualized with all the radiopharmaceuticals
      (RPs). The excretion was mainly via the kidneys except for 99mTc-D, 99mTc-HIG and
      67Ga-Cit. They showed variable amounts of liver and kidney uptake. Similar A/M
      ratios were obtained with all the RPs, reaching max. at 3 h with pertechnetate,
      99mTc-Cit and 99mTc-GP, at 6 h with 99mTc-DTPA and at 24 h with 99mTc-G, 99mTc
      GH, 99mTc-D and 99mTc-HIG. The max. A/M ratios were 3.61 +/- 1.63, 4.61 +/- 3.92,
      5.21 +/- 1.24, 3.60 +/- 0.52, 3.43 +/- 0.92, 5.37 +/- 0.67, 5.98 +/- 1.17 and
      4.76 +/- 2.03 for 99mTc-P, -Cit, -G, -GH, -DTPA, -D, -HIG and 67Ga-Cit,
      respectively. Our results indicated that small molecular weight complexes of
      99mTc can be used in imaging inflammation as well as high molecular weight
      complexes such as 99mTc-D, 99mTc-HIG and 67Ga-Cit. However, the first group is
      preferred, because of rapid blood clearance and excretion predominantly via the
      kidneys, which is an advantage for the identification of abdominal abscesses. The
      main mechanism of accumulation of all the RPs might be a simple diffusion process
      through the injured capillaries. An additional mechanism of binding to proteins
      was considered in view of the increasing concentration ratios with 99mTc-G, -GH, 
      D and -HIG as time progressed.

PMID- 9234275
TI  - The safety and pharmacokinetics in adult subjects of an intravenously
      administered 99mTc-labeled 17 amino acid peptide (CYT-379).
AB  - A phase I study was designed to evaluate the safety and pharmacokinetics of a
      novel platelet reactive peptide, peptide acetyl-SYGRGDVRGDFKCTCCA-amide (CYT
      379), which binds to the fibrinogen receptor of activated platelets and also
      binds to 99mTc. Eleven subjects with suspected deep venous thrombosis had 0.1,
      0.5 or 1.0 mg of the peptide infused intravenously. Pharmacokinetics were
      determined by assaying blood samples in 6 of the 11 subjects and by urine
      sampling in 5 of these 6 subjects. Plasma and whole blood time-activity curves
      demonstrated an initial fast component with half-time clearance of 0.2 +/- 0.01
      and 0.2 +/- 0.02 h and a slow component with half-time clearance of 2.8 +/- 0.3
      and 2.7 +/- 0.2 h (mean +/- SEM for plasma and whole blood, respectively). Urine
      clearance was 22.6 +/- 3.3 and 10.8 +/- 1.6 mL/min when normalized to body
      surface area. The cumulative excretion of 99mTc-CYT-379 in the urine was 16.6 +/-
      3.6, 45.6 +/- 16.9 and 45.6 +/- 1.8% of the administered dose over 0-2, 0-12 and
      0-24 h after radiopharmaceutical injection, respectively. Images obtained in 11
      subjects immediately, at 1-2, and 4-6 h after injection were evaluated for
      abnormalities and were compared with duplex Doppler ultrasonography. 99mTc-CYT
      379 images were positive in only 3 of 7 subjects who had a positive duplex
      Doppler examination in at least one lower extremity. One subject with negative
      duplex Doppler had also negative 99mTc-CYT-379 scintigraphy. One subject with
      negative scintigraphy and two other subjects with positive scintigraphy had no
      other imaging studies of the deep venous system performed. No adverse reactions
      were observed during or after the infusion of 99mTc-CYT-379. 99mTc-CYT-379
      appears to be a safe radiopharmaceutical and demonstrates rapid clearance from
      plasma in human subjects.

PMID- 9234277
TI  - Characterization of [11C]tetrabenazine as an in vivo radioligand for the
      vesicular monoamine transporter.
AB  - [11C]Tetrabenazine ([11C]TBZ) is a new in vivo radioligand for positron emission
      tomographic (PET) imaging of vesicular monoamine transporters. The in vivo
      distribution, metabolism and pharmacological specificity of [11C]TBZ has been
      determined in rodents. Regional mouse brain retention of [11C]TBZ is highest in
      brain regions with greatest monoaminergic innervation (striatum, hypothalamus)
      and can be reduced with ligands for the monoamine vesicular transporter (TBZ,
      ketanserin) but not haloperidol, a dopamine D2 receptor antagonist.
      Chromatographic analysis of rat blood demonstrated rapid metabolism of [11C]TBZ
      to radiolabeled metabolites (alpha- and beta -[11C]dihydrotetrabenazine)
      resulting from reduction of the 2-keto group. These metabolites, as well as a
      third potential metabolite, 9-O-desmethylTBZ, have been synthesized in unlabeled
      form and all three were shown to be capable of greatly reducing in vivo
      accumulation of [11C]TBZ in mouse striatum and hypothalamus. Whole body
      biodistribution of radioactivity after [11C]TBZ injection was determined in rats,
      and the data used to calculate the expected human dosimetry from this
      radiotracer. These studies demonstrated that [11C]TBZ can be safely administered
      for in vivo PET imaging and semi-quantitative determination of vesicular
      monoamine transporters in living human brain, but quantitative pharmacokinetic
      modeling of radioactivity distribution will be complicated by the presence of
      pharmacologically active metabolites.

PMID- 9234279
TI  - PEG-coated lipid vesicles with encapsulated technetium-99m as blood pool agents
      for nuclear medicine.
AB  - Unilamellar lipid vesicles of average diameter 200 nm containing 30 mM
      glutathione were internally labeled with 99mTc using exametazime (HMPAO) to
      transport technetium across the lipid bilayer. Vesicles were prepared both in the
      absence and presence of the lipid-polymer conjugate phosphatidylethanolamine
      monomethoxy polyethylene glycol 5000 (PE-MPEG). Labeling efficiency both in the
      absence and presence of surface polymer was greater than 95% and the vesicles
      retained greater than 95% of their contents when incubated against 50% human
      serum at 37 degrees C for 12 h. When introduced intravenously into rabbits at a
      total lipid concentration of 4 mumol/kg (3.5 mg/kg), radiolabeled vesicles
      without surface polymer were rapidly cleared from the circulation with a half
      life of approx. 30 min and delivered to liver and spleen, however if the lipid
      vesicles were prepared containing 3 or 4.5 mol percent PE-MPEG the circulation
      half-life of the label was approx. 5 and 10 h, respectively, and RES uptake was
      suppressed. These studies confirm a previous report of the utility of exametazime
      for preparing 99mTc-labeled lipid vesicles and demonstrate that extended
      circulation half-lives are achievable for 99mTc-labeled vesicles without recourse
      to high lipid doses and reticuloendothelial blockade. Applications to use
      exametazime as a blood pool marker in nuclear medicine are discussed.

PMID- 9234278
TI  - Novel technetium ligands with affinity for the muscarinic cholinergic receptor.
AB  - The synthesis and preliminary biological characterization of two isomeric
      technetium labeled complexes (2,5,5,9-tetramethyl-4,7-diaza-7-(3' (R)
      quinuclidinylcarboxymethyl)-2,9-decanedithiolato oxo 99/99mtechnetium(V),
      [99/99mTc]-1 and [99/99mTc]-2) designed to exhibit affinity to muscarinic
      cholinergic receptors are described. In vitro binding assays were conducted in
      mouse brain homogenates (whole brain-cerebellum) at 37 degrees C by the
      centrifugation method, where non-specific binding was defined by atropine (1
      microM). The measured affinity (KD) of [99Tc]-1 for mAChR was 1.9 +/- 0.5 microM
      (mean +/- SEM; n = 3) and [99Tc]-2 was 4.5 +/- 0.5 microM (mean +/- SEM; n = 3).
      Scatchard analysis indicated that Bmax values were 10.6 +/- 0.5 and 16.9 +/- 0.5
      pmol/mg tissue, respectively. In competition assays, [99Tc]-1 exhibited an
      apparent affinity (KI) of 16.5 microM (n = 2) against [125I] iododexetimide,
      whereas [99Tc]-2 exhibited an affinity (KI) of 105 microM. In vivo, 0.3% of the
      injected dose of [99mTc]-1 and [99mTc]-2 accumulated in the brain at 5 min after
      injection. These values indicate technetium analogues of neuroreceptor binding
      ligands can be synthesized and retain some affinity for the receptor.

PMID- 9234280
TI  - A novel method for the non-chromatographic purification of technetium-99m-labeled
      monoclonal antibodies: a study with B72.3 monoclonal antibody.
AB  - A cleaning resin has been developed for the non-chromatographic purification of
      99mTc-labeled monoclonal antibodies (MAbs). The resin used is a modified form of
      thiopropylsepharose 6B resin, in which its sulfhydryl groups have been tinylated
      with stannous chloride. The method requires only simple stirring of the
      radiolabeling reaction mixture with this tinylated resin and subsequent
      separation of it from the resin by filtration to obtain a 99mTc-labeled MAb of
      radiopharmaceutical purity. The method provides an alternative to chromatographic
      purification of the radiolabeled MAb (i.e. gel filtration or anion exchange
      chromatography) which has been used in other 99mTc-MAb preparations. For
      comparison studies, we labeled the B72.3 MAb with NeoRx's diamide dimercaptide
      chelate radiolabeling kit, split the reaction mixture into two equal portions and
      then purified one portion with anion exchange chromatography (NeoRx's chosen
      method) while the other portion was purified with our cleaning resin. Comparison
      of HPLC chromatograms, percent 99mTc-bound to MAb, biodistribution and
      scintigraphic results show that our cleaning resin methodology provides a 99mTc
      labeled MAb of essentially equal purity and utility as does the established,
      chromatographic one.

PMID- 9234282
TI  - Evaluation of (-)[18F]fluoroethoxybenzovesamicol as a new PET tracer of
      cholinergic neurons of the heart.
AB  - 18F-labeled (-)fluoroethoxybenzovesamicol [(-)FEOBV] is a novel PET tracer which
      binds to the vesicular acetylcholine transporter of cholinergic neurons. To
      evaluate the in vivo binding specificity and kinetic properties of (-)FEOBV,
      studies were performed in isolated working rat hearts. External gamma,gamma
      coincidence monitoring of hearts indicated high extraction of radiotracer by the
      myocardium and rapid wash-out of unbound tracer (> 90% of maximal accumulation)
      within 5 min. Inclusion of (-)vesamicol (10 microM) throughout perfusion
      decreased the retention of (-)FEOBV by 71% (P < 0.005) and 76% (P < 0.005) in
      atria and ventricles, respectively. However, the initial uptake rate of the
      tracer was unaffected. Additional experiments showed the inactive stereoisomer,
      (+)FEOBV, to have a lower retention than the (-)FEOBV isomer in ventricles,
      indicating stereospecificity of the binding process that is consistent with
      structure-activity relationships of vesamicol congeners. The results indicate (
      )FEOBV to be a moderately specific probe of vesamicol-sensitive binding in
      cholinergic neurons of the heart in experimental conditions that assure adequate
      washout of unbound tracer. However, the utility of the radiotracer for in vivo
      studies with PET is likely to be limited by the low rate of specific binding in
      myocardium consistent with the low density of cholinergic neurons in the heart.

PMID- 9234281
TI  - Comparison of three high affinity SPECT radiotracers for the dopamine D2
      receptor.
AB  - The regional brain distribution and pharmacological specificity of three high
      affinity tracers for the dopamine (DA) D2 receptor: [123I]IBF, [123I]epidepride,
      and [123I]2'-ISP were assessed by SPECT imaging of non-human primates. The ratios
      of striatal-to-occipital activities at the time of peak striatal uptake were 2.2,
      6.3 and 1.7, respectively. From the peak striatal activities, washout rates were
      33, 4 and 16%/h for [123I]IBF, [123I]epidepride and [123I]2'-ISP, respectively.
      The reversibility of the striatal uptake of all three agents was demonstrated by
      the rapid displacement induced by the dopamine D2 selective antipsychotic agent
      raclopride, which increased washout rates to 96, 58 and 43%/h. The administration
      of d-amphetamine, which induces release of dopamine, had no noticeable effect on
      [123I]epidepride but increased the washout rate of [123I]IBF. These results
      suggest that, among these three agents, [123I]epidepride is the superior tracer
      for in vivo displacement studies because of its slow washout and high target-to
      background ratios. However, for tracer kinetic modeling, [123I]IBF may be the
      superior agent because of its early time of peak uptake and its higher target-to
      background ratios than [123I]2'-ISP.

PMID- 9234283
TI  - Synthesis and in vivo evaluation of a 99m/99Tc-DADT-benzovesamicol: a potential
      marker for cholinergic neurons.
AB  - The diaminodithiol (DADT) ligand has been conjugated to the neuromuscular
      blocking agent benzovesamicol (BVM) in the 5-position. DADT-BVM 1 was synthesized
      by coupling of 5-aminomethylbenzovesamicol with a BCA thiolactone reagent. 99mTc
      radiolabeling of 1 with [99mTc]glucoheptonate gave a 4.7:1 mixture of two 99mTc
      complexes as determined by HPLC. Biodistribution data of the major [99mTc]-1
      complex in CD-1 mice (n = 4-5) showed very little uptake and no regional
      selectivity in the mouse brain. At all time points examined, the lung and liver
      showed the highest uptake. For whole brain, the % injected dose values were 0.27,
      0.12, 0.04 and 0.01% at t = 1, 5, 30 and 240 min. The major [99mTc]-1 product
      exhibited a log P = 3.13 +/- 0.06 (SD) with an IC50 = 140-280 nM for the
      corresponding [99Tc]-1 vs (-)-N-[3H]methyl-5-aminobenzovesamicol. The low brain
      uptake of [99mTc]-1 vs 5-iodobenzovesamicol is attributed to its higher molecular
      weight (752) and lower binding affinity.

PMID- 9234284
TI  - Quantitation of radiolabeled antibody binding to cells by thin-layer
      chromatography.
AB  - Thin layer chromatography (TLC) was used to monitor binding of radiolabeled
      antibodies to cells. Labeled antibodies were reacted with cells and aliquots
      chromatographed on serum-blocked, ITLC strips. The cell-antibody complexes remain
      at the origin and unbound antibody migrates with the solvent front. The antibody
      binding was estimated from the ratio of radioactivity at the origin compared to
      the total applied. Separations are completed in about 10 min. This method does
      not use centrifugation or wash steps, and provides an inexpensive and self
      contained system to evaluate radioligand binding. Cell binding assay results
      using this method are approximately the same as those obtained using bead- or
      cell-type assays.

PMID- 9234285
TI  - Synthesis and preliminary evaluation of (R,S)-1-[2-((carbamoyl-4-hydroxy)phenoxy)
      ethylamino]-3-[4-(1-[11C]-met hyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2
      propanol ([11C]CGP 20712A) as a selective beta 1-adrenoceptor ligand for PET.
AB  - The most selective beta 1-adrenoceptor ligand known at this moment is (S)-1-[2
      ((carbamoyl-4-hydroxy) phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2
      imidazolyl) phenoxy]-2-propanol (CGP 26505), the S-isomer of CGP 20712A. We
      prepared the racemic 11C analogue by methylation with [11C]CH3I of the
      corresponding desmethyl compound using a microwave oven to accelerate the
      reaction. Several radioactive by-products (about 70% of the non-volatile
      radioactive products) were formed. After HPLC purification [11C]CGP 20712A with a
      specific activity of 35 TBq/mmol was dissolved in a propylene glycol-ethanol
      saline mixture to prepare it for injection. The total preparation time was 35
      min. The radiochemical yield was 5% (calculated from [11C]CH3I, not corrected for
      decay). The identity of [11C]CGP 20712A was proved by liquid chromatography-mass
      spectrometry (LC-MS). Tissue distribution studies in male Wistar rats have been
      performed. At 20 min after injection of the radioligand (0.1 nmol) the DAR
      [differential absorption ratio = (counts per minute recovered/g tissue)/(counts
      per min injected/g body weight)] in heart tissue decreased significantly (P <
      0.005) from 1.84 +/- 0.11 to 1.21 +/- 0.12 after blocking of beta-adrenoceptors
      with 500 micrograms (R,S)-propranolol. A preliminary PET study in a Wistar rat
      showed maximal uptake in the time frame 10-20 min after injection. The ratio of
      specific/non-specific binding at this interval was 2.6.

PMID- 9234286
TI  - 18F-labelled vesamicol derivatives: syntheses and preliminary in vivo small
      animal positron emission tomography evaluation.
AB  - As possible presynaptic tracers for cholinergic function in humans, three 18F
      labelled vesamicol analogs were synthesized for use in positron emission
      tomography (PET): cis-[18F]-4-fluoromethylvesamicol (FMV), [18F]-N
      fluoroacetamidobenzovesamicol (FAA) and [18F]-N-ethyl-N
      fluoroacetamidobenzovesamicol (NEFA). Radiolabelling was accomplished using
      [18F]fluoride and the corresponding tosylates, the syntheses of which are also
      described. Yields were on the order of 40-60, 5 and 40-60%, respectively. Dynamic
      studies of the biodistribution in rats of [18F]FAA and [18F]NEFA using PET were
      compared with those previously reported for [18F]FMV. Due to probable rapid
      metabolism, [18F]FAA was considered unsuitable as a ligand for in vivo imaging.
      [18F]NEFA, similar to [18F]FAA, displayed a more moderate cerebral uptake than
      that of [18F]FMV (2 vs 20-30%). Pretreatment with vesamicol blocked the cerebral
      uptake, indicating a specific interaction with the vesamicol binding site. The
      biodistribution of high specific activity [18F]NEFA with time could be described
      with a three-compartmental model. The evaluation of [18F]NEFA as a tracer for
      cholinergic function is currently being pursued in monkeys and humans.

PMID- 9234287
TI  - In vivo binding of [125I]NH2-carfentanil to mu opioid receptors in mouse brain.
AB  - A functionalized derivative of the mu opioid agonist carfentanil was synthesized
      (NH2-carfentanil) and showed high specific activity when radiolabeled with
      iodine. [127I]NH2-carfentanil displayed high affinity and pronounced mu-binding
      selectivity with a delta/mu selectivity ratio of over 1200. The ability of
      [125I]NH2-carfentanil to interact in vivo with opioid receptors was determined in
      mouse brain using ex vivo binding techniques. Twenty minutes after
      intraperitoneal injection, 0.1% of the [125I]NH2-carfentanil injected into the
      mouse was present in the brain. [125I]NH2-carfentanil specific binding was
      inhibited by co-injection of naloxone or morphine while naltrindole, a delta
      selective antagonist, was unable to displace the bound radioligand.
      Autoradiographic experiments revealed a heterogeneous distribution of [125I]NH2
      carfentanil specific binding sites, maximal binding occurred in areas with high
      densities of mu receptors. Peripherally administered iodo-NH2-carfentanil
      selectively labelled central mu opioid receptors in mouse indicating great
      potential for single photon emission computed tomography studies.

PMID- 9234288
TI  - Investigation of tumor invasion with [111In]antimyosin.
AB  - Accumulation of [111In]antimyosin in various types of tumors has been reported.
      In order to test the possibility that the destruction of muscle tissue by tumor
      invasion could induce high uptake of [111In]antimyosin, we investigated the
      distribution of [111In]antimyosin in tumor and muscle using autoradiography
      (ARG). High uptake of [111In]antimyosin was observed both in rabbit papilloma VX2
      and rat hepatoma AH109A by scintigraphy and tissue distribution studies, and its
      concentration was found to be highest at the periphery and outer surface of the
      tumors using whole-body ARG. However, in micro- and macro-ARG, high grain density
      was observed in granulation tissue with macrophage infiltration between the tumor
      and muscle, not in the muscle tissue invaded by tumor cell. Significant non
      specific accumulation of [111In]antimyosin in inflammatory tissue surrounding the
      tumor was suggested.

PMID- 9234289
TI  - Quantitative autoradiographic measurement of cocaine-induced regional myocardial
      metabolic changes in hypertensive rats.
AB  - A rat model of hypertensive cardiomyopathy was studied to evaluate the acute
      effects of cocaine on the myocardium. Using autoradiographic microimaging
      techniques, myocardial perfusion (201Tl) and energy substrate utilization
      (glucose: [14C]2-fluoro-2-deoxy-D-glucose-[14C]2DG and fatty acid (15-[p
      iodophenyl])-3-R,S-methyl pentadecanoic acid-[131I]BMIPP) were studied in Dahl
      strain salt-sensitive normotensive and hypertensive rats with and without
      intravenous cocaine. The right ventricle, septum, endocardium and epicardium of
      the left ventricle were analyzed. Increased perfusion (18%) was seen in the
      myocardium of the hypertensive rats as compared to the normotensive rats. There
      was higher [14C]2DG (254%) and lower fatty acid (13.2%) uptake in the
      hypertensive rats, indicative of a shift from aerobic to anaerobic substrate
      utilization. In cocaine-treated normotensive rats, a generalized decrease in
      myocardial perfusion (30%) and increased glucose metabolism (89%) was seen. In
      cocaine-treated hypertensive rats, the increased myocardial perfusion (16%) was
      heterogeneous and was more pronounced in septum and epicardium. The endocardium
      and epicardium in the hypertensive rats showed an overall increase (23%) in
      glucose utilization after cocaine which was not as dramatic as was seen in the
      normotensive heart and a slight increase in fatty acid utilization. These results
      are consistent with prior observations that under pressure overload the
      myocardium responds non-uniformly. It may well be that the hypertensive
      cardiomyopathic heart is unable to respond to the challenge of cocaine by further
      increasing glucose utilization. These data obtained in an animal model of
      hypertension seem to indicate that hypertension may increase the risk of cardiac
      complications related to cocaine.

PMID- 9234290
TI  - 99mTc-insulin: labeling, biodistribution and scintiimaging in animals.
AB  - Porcine insulin was labeled with 99mTc by direct tin reduction. More than 95%
      labeling efficiency was obtained on paper chromatography in saline and methyl
      ethyl ketone. The stability of the labeled compound was confirmed by paper
      chromatography at 3 h post-labeling and by human serum albumin (HSA) challenge.
      PAGE pattern indicated no change in the electrophoretic behavior and the
      molecular size of insulin after the labeling procedure. Biodistribution in rats
      shows that kidney took up the maximum amount of 99mTc-insulin; maxima being
      maintained throughout 24 h post-injection. Liver and intestine were the other
      organs with significant uptake; the rest localizing little or negligible
      radioactivity. Most of the radioactivity was excreted via the renal pathway into
      urine. Scintiimages conformed to the biodistribution data. The results of this
      study present the potential of 99mTc-labeling of insulin by a simple method.

PMID- 9234291
TI  - Synthesis and biodistribution of [5-131I]iodotropapride: a potential D2 dopamine
      receptor imaging agent.
AB  - [5-131I]Iodotropapride is a benzamidic compound which displays high affinity and
      selectivity for dopaminergic receptors. It was prepared from the corresponding
      brominated compound by a nucleophilic substitution with [131I]iodine (t1/2 = 8.02
      days, E gamma = 364 keV) based on the use of Cu(I) as catalyst and high specific
      activity of [131I]NaI. After i.v. injection in rats the tracer crosses the blood
      brain barrier (0.42 +/- 0.06% of injected dose in the total brain) and
      demonstrates a high affinity binding to the striatum. The striatum-to-cerebellum
      ratio increases with time and reaches values of 9 and 22 at 30 and 120 min after
      injection, respectively. This specific uptake in the striatum is saturable and
      can be blocked by pretreatment with different D2 antagonists. When labeled with
      123I (t1/2 = 13 h, E1 = 159 keV), the corresponding [123I]iodotropapride may be
      useful for the investigation of the D2 dopamine receptors in humans with single
      photon emission computer tomography (SPECT).

PMID- 9234292
TI  - Synthesis, characterization and biodistribution of new 99mTc oxo and nitrido
      complexes with bi- and tetradendate unsaturated NS and N2S2 Schiff bases derived
      from 2-aminocyclopentene-1-dithiocarboxylic acid as potential heart imaging
      agents.
AB  - The synthesis, characterization and 99mTc labelling of unsaturated diamino
      dithiol ligands with methyl dithiocarboxylate functions: 2-aminocyclopentene-1
      dithiocarboxylic methyl ester (H2L1), N,N'-ethylene bis(methyl 2
      aminocyclopentene-1-dithiocarboxylate) (H2L2) and N,N'-propylene bis (methyl 2
      aminocyclopentene-1-dithiocarboxylate) (H2L3) are described. Cationic oxo (Tc =
      O) and neutral nitrido (Tc = N) complexes were obtained. Biodistribution studies
      in rat showed a good heart uptake of 99mTcN-L2 (2% ID at 5 min) with a high heart
      to-blood ratio (5.8 at 5 min), but this complex also exhibited high lung and
      liver uptake.

PMID- 9234293
TI  - Metabolic pathway of 2-deoxy-2-[18F]fluoro-D-talose in mice: trapping in tissue
      after phosphorylation by galactokinase.
AB  - To make clear the metabolic fate of 2-deoxy-2-[18F]fluoro-D-talose ([18F]FDT) in
      animals, the in vivo and in vitro metabolism of non-radioactive 2-deoxy-2-fluoro
      D-talose (FDT) was investigated by 19F-NMR spectroscopy. Based on the 19F-NMR
      spectral analyses, 2-deoxy-2-fluoro-alpha-D-talose-1-phosphate (FDT-1-P) was
      identified as a single metabolite in the organs of tumor-bearing mice after FDT
      administration (60 mg/kg). In the liver, almost all FDT was converted to FDT-1-P
      within 10 min after FDT injection and the phosphate form remained unchanged for
      at least 3 h. FDT was well converted to FDT-1-P by galactokinase in vitro. The
      FDT-1-P formed, however, failed to convert to a uridylate derivative by treatment
      with galactose-1-phosphate uridyltransferase. The observed low affinity of
      galactose-1-phosphate uridyltransferase for the FDT-1-P could account for the
      accumulation mechanism of FDT-1-P in vivo. Similar metabolic studies of [18F]FDT
      with radio-TLC demonstrated the [18F]FDT-1-P as a single metabolite of [18F]FDT
      in the mouse liver. These results indicate that [18F]FDT enters a D-galactose
      metabolic pathway and undergoes a metabolic trapping in the [18F]FDT-1-P form by
      galactokinase in the tissues such as liver and tumor. Consequently, [18F]FDT is
      expected to be a new radiopharmaceutical for the measurement of galactokinase
      activity by positron emission tomography.

PMID- 9234294
TI  - A simplified kit for instant preparation of technetium-99m human immunoglobulin-G
      for imaging inflammatory foci.
AB  - A kit consisting of reduced human immunoglobulins G (hIgG), methylene
      diphosphonate, stannous chloride and ascorbic acid has been developed to
      instantly produce technetium-labelled hIgG of greater than 97% purity and
      suitable for inflammation foci scintigraphy in patients. The shelf life of the
      kit when stored at 4-7 degrees C was at least 3 months. 99mTc-hIgG prepared from
      the kit, when incubated at 37 degrees C for 24 h in physiological saline and
      human serum was found to degrade by only 7.8 and 4.3%, respectively, thereby
      indicating high stability of the labelled product. Competitive RIA data did not
      exhibit loss of immunoreactivity of the hIgG due to its reduction. Blood
      clearance of the radiopharmaceutical in rabbits exhibited a monophasic
      exponential pattern. Biodistribution in mice showed uptake by liver (4.93%),
      kidneys (3.07%) and intestines (2.12%) at 4 h which was reduced to 1.99, 2.18 and
      1.93%, respectively at 24 h. Radiolabelled hIgG prepared from the kit was found
      to be quite satisfactory for inflammation scintigraphy in human patients.

PMID- 9234295
TI  - Investigation of [67Ga]dimethylgallium(III) acetylacetonate as a potential
      radiopharmaceutical.
AB  - Carrier-added [67Ga]dimethylgallium(III) acetylacetonate, a four coordinate Ga
      complex with two hydrolytically-stable Ga-C bonds, was prepared at a specific
      activity of 2.8 mCi/mmol. The biodistribution of this tracer was determined
      following intravenous injection into rats as a 5% ethanol: 19% propylene glycol
      solution in saline. Although the myocardial levels of 67Ga were fairly constant
      over a 2 h time period (%ID/heart = 0.80 +/- 0.19, 0.67 +/- 0.04 and 0.62 +/-
      0.07 at 1.30 and 120 min post-injection, respectively), somewhat slow clearance
      of activity from the blood would preclude the use of this organometallic gallium
      complex as a myocardial imaging agent.

PMID- 9234296
TI  - IGFs and their binding proteins.
AB  - Insulin-like growth factors (IGFs), initially known as somatomedins, and their
      specific, high-affinity binding proteins (IGFBPs) are synthesized in most
      tissues, but principally in the liver. The interest of measuring their
      circulating levels, which reflect liver production, is to obtain indications as
      to their endocrine function and regulation. IGF-I plays a pivotal role in post
      natal growth. Its half-life is significantly increased by its association with
      IGFBPs and its serum levels reflect somatotropic status, unlike growth hormone
      (GH) which has a much shorter half-life and whose secretion comes in pulses.
      Since investigation of growth retardation must include the most finely tuned
      appreciation possible of somatotropic secretion, assays of IFG-I and
      electrophoretic analysis of IGFBP profile can be useful tools, both
      diagnostically and therapeutically, and can help in determining the need or
      otherwise for GH treatment, especially in view of the growing demand for such
      therapy.

PMID- 9234298
TI  - Heterogeneity of human prolactin. Influence on immunoassays (RIA and IRMA).
AB  - Plasma hPRL consists of a complex mixture of molecular forms. The monomeric form,
      derived from the pituitary, is the main form. Others (dimeric or oligomeric) can
      form de novo in plasma. Recently, BBPRL (big big PRL) has been identified in some
      cases as an antiPRL autoantibody, but these data require further investigation.
      The PRL forms are differently recognized by immunoassays (IRMA and RIA) and are a
      source of inter-assay discrepancy.

PMID- 9234297
TI  - Origin and significance of the heterogeneity of protein hormones.
AB  - The heterogeneity of circulating protein hormone is the result of multiple steps
      including gene expression, mRNA maturation, post-translational processing and
      peripheral catabolism. As a consequence of these cumulative events, it seems
      difficult to evaluate the endocrine function by using specific radioimmunoassays
      for each circulating variant of a protein hormone. Moreover, the discovery of new
      molecular variants of protein hormones with unknown biological significance
      complicates the standardization and the clinical interpretation of immunoassays.

PMID- 9234299
TI  - Determination of circulating parathyroid hormone levels and differential
      diagnosis of hypercalcemia.
AB  - Primary hyperparathyroidism is the most frequent cause of hypercalcemia in
      outpatients. In contrast, this electrolyte disorder is very often associated with
      cancer when detected in hospital, particularly in the frame of tumors of breast,
      lung or lympho-hematopoietic system. Hypercalcemia results from an imbalance
      between the fluxes of calcium entering and leaving the extracellular space.
      Theses fluxes, mainly those at the levels of bone and kidney, are the main
      regulators of calcium homeostasis. Depending on the etiology, increases in either
      bone resorption or renal tubular calcium reabsorption can predominate as the
      cause of elevated calcemia. Thus, an increment of renal tubular reabsorption of
      calcium plays a prominent role in hypercalcemia resulting from increased serum
      concentrations of parathyroid hormone, but can also be detected in 50% of
      malignant hypercalcemias. The ectopic production of authentic parathyroid hormone
      has convincingly been demonstrated in very few cases. The syndrome of
      pseudohyperparathyrodism encountered in malignant hypercalcemia can be accounted
      for by the tumoral secretion of an analog of parathyroid hormone, parathyroid
      hormone-related protein. Both proteins, which are produced by different genes
      located on different chromosomes, interact with the same cell membrane receptors
      and display identical spectrum of actions. Since they are immunologically quite
      distinct, there is no cross-reactivity in the various competitive or radiometric
      immunoassays actually available. The determination of circulating levels of
      parathyroid hormone is an essential step in the differential diagnosis of
      hypercalcemias, provided the assays offer adequate sensitivity and specificity.
      Nowadays, this appears to be generally the case.

PMID- 9234300
TI  - Heterogeneity of plasma gonadotropins. Consequences on immunological properties
      of LH.
AB  - The pituitary gonadotropins FSH and LH are secreted into blood as dimeric
      glycoproteins which display a wide heterogeneity when submitted to technique of
      separation based on electric charge. That supports the assumption of a major role
      of the carbohydrates moieties as a source of heterogeneity. No clear difference
      however has been demonstrated in the biological potency of the different isoforms
      occurring in blood. On the contrary, important discrepancies in immunological
      activity have been evidenced, mainly as far as LH is concerned. This is
      particularly important from a practical point of view since some monoclonal
      sandwich assays widely used for the measurement of LH levels fail to detect LH in
      samples from certain subjects. The description of the so-called "invisible LH"
      phenomenon should prompt international organizations to incite the manufacturers
      of commercial kits to improve the standardization in gonadotropin assays.

PMID- 9234301
TI  - Heterogeneity of circulating calcitonin levels: relations with calcitonin
      biosynthesis in medullary thyroid carcinomas.
AB  - Calcitonin (CT), a hypocalcemic and hypophosphatemic hormone, is produced by the
      C-cells of the thyroid gland. It is the main tumoral marker of medullary thyroid
      carcinoma (MTC). Hypersecretion of CT is also associated with other types of
      tumors. Thus, heterogeneity of circulating CT can play an important role in the
      accurate determination of hormone levels in blood samples obtained from MTC
      patients. Further studies will be necessary to establish the predictive value of
      the several peptides coded by the calcitonin gene family. All of them
      specifically reflect the ways and the pattern of alternative splicing of the
      primary transcript of the Calc I gene. Such relations implicate further
      investigations concerning the relationship between calcitonin circulating levels,
      biosynthetic activity of C-cells and the expression of gene encoding for this
      hormone, in normal and neoplastic conditions.

PMID- 9234302
TI  - Heterogeneity of circulating growth hormone.
AB  - Human growth hormone (GH) represents a family of related proteins arising from
      two genes, alternative mRNA splicing, and several post-translational
      modifications. In addition, post-secretory events occur when GH enters the
      circulation. The full scale of GH heterogeneity is only beginning to be
      appreciated, and new GH forms or related proteins may be discovered in the
      future. GH measurements are affected by GH heterogeneity. Immunoassays are
      influenced by the mixture of GH variants, but are not sensitive to GH binding
      proteins (GHBPs). In contrast, radioreceptor assays are sensitive to both GH
      variant mixtures and to the high affinity GHBP. It is hoped that in the future,
      these problems can be minimized by rigorous characterization of existing
      antibodies with respect to epitope recognition on various GH forms, and
      ultimately, by production of GH variant-specific antibodies that permit direct
      and individual assessment of the circulating members of the GH family.

PMID- 9234303
TI  - Apparent growth hormone levels in plasma and urine. Methodological "artefacts".
AB  - Urinary growth hormone reflects plasma levels, if a normal renal function is
      assured. It offers the advantages of easy repetition over prolonged periods of
      time. It is an easy tool to assess physiological and pathophysiological aspects
      of the "amount" of growth hormone secreted in a given clinical situation. It can
      be used to control therapy and reassess the "growth hormone status" at any time
      during a treatment period. It cannot, however, replace the assessment of
      responses of the system to a given stimulus and will not reflect the pulsatility
      of plasma levels.

PMID- 9234304
TI  - Present and potential uses of growth hormone in therapeutics.
AB  - In the first weeks of 1993, the accepted indications of growth hormone remain
      limited to the treatment of severe growth failure resulting directly from
      pituitary somatrotropic deficiency and to the improvement of height in Turner
      syndrome. Various other indications of GH may be considered as "potential". Each
      one has still to prove its real usefulness at more or less long term. Moreover,
      for all of them there will have to largely take into account the ethical side,
      mainly the ratio between the expected beneficial effects and the costs and
      burden, even if no serious inconveniences are presently known. The possible
      increase in the use of growth hormone is an extremely serious scientific
      question. It is important to keep it out from the changes in subjective opinions,
      the medical faschions, and the influences of public opinion or media.

PMID- 9234305
TI  - Overview: diagnostic tests for viral infections transmitted by blood.
AB  - The risk of transmitting viral infections by transfusion today is quite remote.
      The many, sensitive, diagnostic tests in place, when applied to the blood of
      volunteer, unpaid (unremunerated), unpressured donors who are also carefully
      evaluated at the time of donation, make blood and blood component transfusions
      very safe. A number of sensitive laboratory tests are performed on each unit of
      donated blood and plasma to reduce the risk of transmission of hepatitis viruses
      and retroviruses from asymptomatic donors to transfusion recipients. With the
      tests, we hope to catch otherwise undetectable individuals who may be carrying
      these viruses yet appear healthy and deny risk factors for their carriage.
      However, the laboratory tests in use in blood banks were designed to aid in the
      diagnosis of patients with viral diseases. Therefore, a reactive test, even if
      reproducible, on a sample from a healthy blood donor is more apt to be falsely
      than truly positive. An ideal microbiologic test is one which is one hundred
      percent sensitive, i.e., it will identify every person with an infectious disease
      (including asymptomatic carriers). In addition, a perfect test would have one
      hundred percent specificity, i.e., it would not be reactive in anyone without the
      infectious agent. The decision point or "cutoff" for an ideal test would be above
      the (negative) results for all normal and uninfected samples, but below that for
      all (positive) infectious ones. In reality, there is an overlap between some of
      the results on normals and those on diseased individuals, including persons who
      are carrying an infectious agent. When we try to obtain maximal sensitivity,
      e.g., to detect all asymptomatic carriers of a virus, the assay cutoff is set
      very low for tests applied to blood donors; but this approach will compromise the
      specificity of a test. The net effect is that many normal people donating blood
      are said to have "abnormal" test results which, among other things, necessitates
      the loss of their blood and plasma. In addition, we must follow up the reactive
      results by enzyme linked immunoassays (EIA or ELISA) or radioimmunoassays (RIA)
      used to screen or preliminarily test blood from donors with supplemental or
      confirmatory tests to verify whether the initial test is a true positive or a
      false positive one. Trying to explain the significance of a false positive test
      for AIDS or hepatitis to a healthy donor often causes fear, concern and/or anger.
      Thus, the use of very sensitive tests on blood donors will increase the safety of
      transfusion for recipients but result in loss of some donors and discard of many
      blood components unnecessarily. Despite the problems in applying sensitive tests
      to asymptomatic individuals who are not patients, the assays in place in blood
      banks have, nonetheless, resulted in remarkably small risks of virus transmission
      by transfusions. Currently, the risk of HCV infection following a transfusion is
      about 1 in 3,300 per unit transfused. This is an enormous improvement compared to
      the risks of what was called non-A, non-B hepatitis in the 1970s and 1980s before
      the use of the test for antibodies to HCV. For HTLV-1 (and, potentially, HTLV-II)
      the risk of transfusion transmission is about 1 in 50,000 per unit of screened
      blood. Using blood which is anti-HIV-1/2 non-reactive, the risk is about 1 in
      225,000 units of transmitting HIV. The risk of transfusion associated AIDS is
      thus quite remote in 1993. For hepatitis B virus, only about 1 in 200,000 units
      of blood transmit this virus now. In sum, only about 3 units of blood per 10,000
      of those collected from acceptable, volunteer donors are currently likely to
      transmit a serious or fatal transfusion-transmitted viral infection. In contrast,
      in America, about 6 out of every 1,000 patients hospitalized will die from an
      accidental or preventable cause other than the underlying disease for which
      he/she was hospitalized. (ABSTRACT TRUNCATED)

PMID- 9234306
TI  - Serological diagnosis of HTLV-I/II infections in France.
AB  - During the last years, important improvements have been made in the field of HTLV
      I/II serodiagnosis. The screening tests, which combine higher performances of the
      sensitivity towards HTLV-I and HTLV-II samples, and better specificity, are
      manifold. The criteria of positivity by western-blots have been reinforced. As
      for HIV, some western-blot profiles with no evolution on two successive samples,
      correspond to non specific HTLV reactions. HTLV-I/II serotyping is easier than
      before. More effective tools will certainly be available in the coming years for
      the Blood Transfusion Services and the physicians.

PMID- 9234307
TI  - Diagnosis of viral hepatitis with a nonisotopic hybridization assay.
AB  - The DNA enzyme immunoassay is an efficient method for the screening of PCR
      products derived from different hepatitis virus genomes, and allows to bypass
      both agarose gel electrophoresis and Southern blot hybridization with
      radioactively labeled probes. A wider application of this method will disclose
      new perspectives for the introduction of PCR in clinical laboratories.

PMID- 9234308
TI  - Prognostic factors and variant estrogen receptor RNAs in clinical breast cancer.

PMID- 9234309
TI  - 'Oncocheck': an international external quality assessment scheme for immunoassays
      of tumor markers.
AB  - Starting from November 1990, an international External Quality Assessment Scheme
      (EQAS) for immmunoassays of tumor markers has been organized. Presently, 238
      laboratories from France, Germany, Italy, Japan and Spain participate in the
      scheme. In this report the main features of the EQAS and data processing are
      outlined. Results collected during the 1992-cycle allow evaluation of the state
      of the art of AFP, CEA, CA 19-9, CA 15-3, CA 125 and PSA immunoassays. According
      to their analytical performances, the 6 tumor marker immunoassays can be
      classified into several groups, the first including AFP and CA 15-3 for which
      both total variability and within-kit agreement are good. For CEA assay,
      performance can be considered as satisfactory even though further improvements of
      between-lab agreement would be welcome. For the 3 other tumor markers, the higher
      total variability indicates an urgent need for a better standardization by
      improvement of either both within-kit and between-kit agreements (CA 19-9) or
      between-kit agreement mainly (PSA, CA 125).

PMID- 9234310
TI  - Immunoassay: recent developments and future directions.
AB  - All analytical techniques employed in the biological sciences rely on recognition
      of the shape and structure of molecules of the substance of interest (the
      analyte). Such molecular recognition and sensing usually relies on the use other
      molecules possessing a complementary structure, implying a specific lock and key
      relationship between the two. Antibodies comprise a class of recognition
      molecules evolved by nature for the purpose of bodily defence, and are clearly of
      particular utility in this context. However techniques of increasing
      sophistication (including the techniques of molecular biology) are currently
      being developed which enable the artificial construction of antibody-like
      molecules possessing improved molecular recognition properties which can be
      harnessed for microanalytical purposes. Oligonucleotide probes likewise exhibit
      the property of binding to complementary nucleotide sequences, and the techniques
      of, for example, in situ hybridisation therefore share many features with
      immunoassay techniques. Microanalytical techniques relying on binding reactions
      between substances possessing complementary lock and key molecular structures are
      unlikely to be superseded within the foreseeable future, only the labels used to
      monitor such reactions, and the means of production of "recognition molecules",
      being subject to further development. Such techniques already enter into all
      areas of life, including medicine, agriculture, etc, and are likely to increase
      further in importance with increasing concern regarding chemically complex
      contaminants in food, the environment, etc. Developments in this field are
      clearly directed to slightly differing objectives as indicated in this
      presentation. These include methodological simplification (making the techniques
      cheaper and more widely available), improvements in sensitivity (to enable the
      detection and measurement of substances beyond the reach of current methods) and
      the construction of transducer-based sensor methods (permitting, inter alia, the
      monitoring of changing analyte concentrations). However the combination of the
      "ultrasensitivity" of current single analyte assay methods with the ability
      simultaneously to determine multiple analytes in the same sample represents, in
      my view, the next major methodological challenge in this field, and--if
      successfully addressed--will constitute a quantum advance on present analytical
      methods. Indeed the development of miniaturised multianalyte binding assay
      techniques may ultimately comes to be seen as analagous to, for example, the
      introduction of the word processor, and other similar major technological
      advances of the past decade.

PMID- 9234311
TI  - Diagnosis of thyroid dysfunction: present and future.
AB  - Thyroid disorders represent the second most common endocrine disorder after
      diabetes mellitus. For this reason, investigation of thyroid function is
      frequently carried out, taking advantage of numerous tests currently available.
      It it the physicians's difficult task to select the most appropriate assay(s) in
      the different pathophysiological conditions from the bewildering array of thyroid
      function tests, in order to satisfy optimal diagnostic standards, but also to
      fulfill cost/benefit criteria. Aim of this paper is to provide a brief overview
      of advantages and disadvantages of main thyroid function tests, and to suggest a
      testing strategy for the diagnosis of suspected thyroid dysfunction.

PMID- 9234312
TI  - Cytokines and organ transplantation. A review.
AB  - Cytokines regulate both aspecific inflammatory responses and specific immune
      responses. Inflammatory changes occur in the organ transplant as a result of
      tissue trauma and ischemia/reperfusion in the organ donor and at the time of
      transplant operation. There is a possibility that cytokines play a role in
      mediating theses changes. These aspecific inflammatory changes may not only
      affect graft function but also influence graft immunogenicity (enhanced MHC and
      adhesion molecule expression) and thus, vulnerability to rejection. Cytokines
      orchestrate the specific immune response elicited by organ transplantation.
      Relevance of cytokines to the rejection reaction is multifactorial in nature: 1)
      promotion of the proliferation an differentiation of specific alloreactive T and
      B cells clones and differentiation and activation of CTL and NK cells, 2)
      chemotactic effect and induction of the expression of adhesion molecules, 3)
      enhancement of MHC class I and II expression, and 4) direct cytotoxic effect on
      the target grafted cells. Therefore, modulation of cytokine activity either
      specifically (monoclonal antibody, soluble receptor, etc.) or aspecifically
      (cyclosporin, FK 506, Rapamycin, steroids, etc.) is essential in controlling
      graft rejection. Determination of circulating cytokines and cytokines measurement
      within the biological fluids produced by an organ transplant may help in the
      diagnosis of rejection episodes and other complications following organ
      transplantation.

PMID- 9234313
TI  - Immunochemical methods for environmental monitoring.
AB  - Immunochemical methods for environmental analysis must be taken into
      consideration more for their ability to expand the potential of analytical
      measures rather than for substituting current methodologies. Moreover, the full
      potential of these methods has yet to be realized. Indeed, the terms and concepts
      of immunology are new to most analytical chemists, even if environmental science
      has always been an interdisciplinary field. On the other hand, the clinical
      development of immunoassays means that much experience has been gained in the
      analysis of blood, urine, and tissue samples. The immunochemical analysis of
      samples from soils, ground water, waste chemicals, poses new challenges in sample
      preparation that have yet to be extensively studied, and in the future there may
      be immunoassays better suited for the particular problems associated with
      environmental monitoring.

PMID- 9234314
TI  - Synthesis of the enantiomers of [N-methyl-11C]PK 11195 and comparison of their
      behaviours as radioligands for PK binding sites in rats.
AB  - The enantiomers of [N-methyl-11C]PK 11195, a radioligand for PET studies of PK
      (peripheral benzodiazepine) binding sites, have been prepared from the newly
      synthesized N-desmethyl-enantiomers by 11C-methylation with N.C.A.
      [11C]iodomethane. The brain uptake and retention of each enantiomer was compared
      with that of the racemic radioligand after i.v. administration into normal rats
      and into rats with focal cortical lesions. No significant differences in the
      uptakes of the enantiomers were observed in regions devoid of PK binding sites.
      However, the R-enantiomer was retained to a significantly greater extent than the
      S-enantiomer in olfactory bulbs-tubercles, which contain some PK binding sites,
      and also in 9-day-old focal cortical lesions, which are greatly enriched in PK
      binding sites associated with macrophage infiltration. The observed differences
      are consistent with the approximately 2-fold greater affinity of the R-enantiomer
      for PK binding sites reported in vitro and imply that the use of this enantiomer
      would have advantages over the use of the racemate currently used for PET
      studies.

PMID- 9234315
TI  - In vivo metabolism of the technetium isonitrile complex [Tc(2-ethoxy-2-methyl-1
      isocyanopropane)6]+.
AB  - Technetium(2-ethoxy-2-methyl-1-isocyanopropane)6+, [Tc-EIBT] is a complex of
      technetium(I) structurally similar but slightly more lipophilic than the
      commercial myocardial perfusion agent Cardiolite [Tc-MIBI]. Tc-EIBI exhibits
      rapid extraction from the blood into heart, liver, kidney and striated muscle and
      rapid hepatobiliary clearance. In the guinea pig, unlike Tc-MIBI, this compound
      is almost completely enzymatically metabolized to numerous cationic complexes
      containing a mixture of ethyl other and hydroxy isonitrile ligands. Substitution
      of the ethyl other group for a methyl ether produces an agent that shows
      selective in vivo metabolism and more rapid clearance from the liver.

PMID- 9234316
TI  - Receptor binding radiotracers for the angiotensin II receptor: radioiodinated
      [Sar1, Ile8]Angiotensin II.
AB  - The potential for imaging the angiotensin II receptor was evaluated using the
      radioiodinated peptide antagonist [125I][Sar1, Ile8)angiotensin II. The
      radioligand provides a receptor-mediated signal in several tissues in rat
      (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney
      cortex should be sufficient to permit imaging, at least via SPECT. The
      radiotracer is sensitive to reductions in receptor concentration and can be used
      to define in vivo dose-occupancy curves of angiotensin II receptor ligands.
      Receptor-mediated images of [123I][Sar1, Ile8]angiotensin II were obtained in the
      rat kidney and Rhesus monkey liver.

PMID- 9234317
TI  - Synthesis and radioiodination of a nido-1,2-carboranyl derivative of 2
      nitroimidazole.
AB  - The synthesis of a nido-carboranyl congener of misonidazole, 1-(3'-nido
      carboranyl-2'-hydroxy)propyl-2-nitroimidazole, has been carried out. Alternative
      methods of preparations were conducted to optimize the chemical yield, with a
      five step synthesis giving an overall yield (from 1,2-carborane) of 36%. A
      diastereomeric pair of nido-carboranyl compounds was obtained. The diastereomeric
      nido-carboranyl misonidazole congeners were (radio)iodinated to yield (> 90%) a
      mixture of diastereomeric compounds in which the iodine had bonded to a boron
      atom on the nido-carborane moiety. These compounds will be investigated for their
      application to boron neutron capture therapy (BNCT) and hypoxia imaging of
      cancer.

PMID- 9234318
TI  - Effects of ischemia-reperfusion injury on myocardial single pass extraction and
      retention of Cu-PTSM in perfused rat hearts: comparison with 201T1 and 14C
      iodoantipyrine.
AB  - The effects of ischemia-reperfusion-induced myocardial damage on the single pass
      extraction and retention of 64Cu-pyruvaldehyde-di(N4-methylthiosemicabazone)
      (64Cu-PTSM) in perfused rat hearts were compared to these effects on that of
      201T1 and 14C-iodoantipyrine. 201T1 and 14C-iodoantipyrine did not show
      significant changes, but in the case of 64Cu-PTSM, the single pass extraction and
      retention was reduced with reperfusion. These findings indicate that ischemia
      reperfusion-induced myocardial damage decrease the generator-produced 62Cu
      labeled 62Cu-PTSM extraction and retention, and that 62Cu-PTSM might have
      potential not only as a blood flow tracer but also as a functional tracer.

PMID- 9234319
TI  - Evaluation of a direct method for technetium labeling intact and F(ab')2 1A3, an
      anticolorectal monoclonal antibody.
AB  - A direct method for 99mTc-labeling monoclonal antibodies (MAb) has been evaluated
      for labeling intact and F(ab')2 1A3, an anticolorectal carcinoma MAb. The method
      employs ascorbic acid to reduce the MAbs. By altering the reaction conditions for
      99mTc-1A3, a maximum radiolabeling yield of 48% was obtained with an
      immunoreactivity (IR) value of 87%; and for 99mTc-1A3-F(ab')2, a yield of 49% and
      an IR value of 70% was obtained. Biodistribution of 99mTc-labeled 1A3 MAbs was
      performed in a Golden Syrian hamster model and compared to 125I-labeled 1A3 MAbs.
      Tumor uptake (%ID/g) was significantly better for the intact 125I-1A3 at 24 h
      post-injection compared to the intact 99mTc-1A3. For 99mTc-1A3-F(ab')2, %ID/g
      tumor was low, and did not increase over 24 h. High %ID/g kidney persisted at 24
      h for both 99mTc-labeled intact and F(ab')2 1A3. Serum stability was performed in
      Sprague-Dawley rats for the 99mTc-labeled 1A3 MAbs, and compared to 125I-labeled
      1A3 MAbs, which showed intact 99mTc-1A3 cleared similarly to 125I-1A3, and 99mTc
      1A3-F(ab')2 cleared more rapidly than 125I-1A3-F(ab')2 indicating instability of
      the 99mTc-labeled 1A3-F(ab')2.

PMID- 9234320
TI  - Fluorine-18-labelled NCQ 115, a selective dopamine D-2 receptor ligand.
      Preparation and positron emission tomography.
AB  - NCQ 115 ((+)-(R)-5-bromo-N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)-2, 3
      dimethoxybenzamide) is a selective dopamine D-2 receptor antagonist. NCQ 115 has
      a fluorine in a synthetically suitable position in the parent compound and was
      therefore suggested as a potential 18F-labelled radioligand for positron emission
      tomography (PET). [18F]4-Fluorobenzyl iodide was prepared in a 3-step synthesis
      from [18F]fluoride. N-4-Fluorobenzylation of the corresponding secondary
      pyrrolidine precursor was performed in DMF followed by purification with semi
      preparative HPLC. The total radiochemical yield (EOB and decay-corrected) was 15
      20% with a total synthesis time of 90 min and a radiochemical purity > 99%. The
      specific radioactivity at the end of synthesis (EOS) was about 1500 Ci/mmol (55.5
      GBq/mumol). [18F]NCQ 115 was injected into a Cynomolgus monkey for PET
      examination of brain in vivo. There was a conspicuous uptake of radioactivity in
      the monkey striatum. A specific [18F]NCQ 115 binding reached a peak after about
      60 min which indicates equilibrium.

PMID- 9234321
TI  - Synthesis of 2-[18F]fluoro-2-deoxy-L-glucose and positron emission tomography
      studies in monkeys.
AB  - 2-[18F]Fluoro-2-deoxy-L-glucose was synthesized from its trifluoromethanesulfonyl
      precursor. The precursor was prepared by selective acetylation and triflation of
      L-mannose. L-Mannose was first treated with acetic anhydride in the presence of a
      catalytic amount of perchloric acid and then reacted with phosphorus tribromide
      followed by aqueous sodium acetate to produce pure 1,3,4,6-tetra-O-acetyl-a-L
      mannopyranose in 32% yield. This compound was treated with
      trifluoromethanesulfonic anhydride and pyridine in methylene chloride to form
      1,3,4,6-tetra-O-acetyl-O-tritrifluoromethanesulfonyl-a-L-mannopyra nose in 77%
      yield. Nucleophilic substitution of the triflate with 18F-in the presence of
      Kryptofix 2,2,2 followed by acid hydrolysis produced 2-[18F]fluoro-2-deoxy-L
      glucose with a radiochemical yield of 20-30% (EOS) within 90 min. Biodistribution
      studies in rats and PET imaging in Rhesus monkeys demonstrated that this sugar
      analog distributes in the extracellular space of most organs but is excluded from
      the CNS.

PMID- 9234322
TI  - Bis-benzimidazole dyes, Hoechst 33258 and Hoechst 33342: radioiodination, facile
      purification and subcellular distribution.
AB  - A simple HPLC method is presented for the purification of DNA binding bis
      benzimidazole dyes Hoechst 33258, Hoechst 33342 and 131I-iodoHoechst 33258. The
      mobile phase, consisting of methanol and aqueous ammonia (0.2%) in the ratio 2:3,
      resolved and separated the radiochemical from unlabeled ligand and other reagents
      used in the reaction, thereby resulting in high radiochemical purity and yield.
      The iodinated Hoechst 33258 did not show any selective binding to nuclear DNA
      when cell fractionation studies were performed with cultured mammalian cells as
      well as in mice testes. Fluorescence microscopy studies with V79 cells stained
      with these dyes, showed the superiority of Hoechst 33342 in selective
      localization in nuclear DNA compared to Hoechst 33258. The difference in behavior
      of these two dyes in terms of binding to nuclear DNA, and hence their ability to
      provide protection against damage caused by ionizing radiation, may be explained
      on the basis of the molecular charge. The high chemotoxicity of Hoechst 33342
      observed in the present studies suggests that its usefulness as a radioprotector
      against chronic irradiation of tissue by incorporated radionuclides may be
      limited.

PMID- 9234323
TI  - Preparation of a pure 99mTc-F(ab')2 radioimmunoconjugate by direct labeling
      methods.
AB  - Intact IgG and Fab' can be labeled directly with 99mTc to give quantitative
      incorporation of radioactivity into the protein. With F(ab')2 the reductive
      conditions yield a mixture of 99mTc-F(ab')2 and 99mTc-Fab'. We now report a
      direct labeling method to produce only 99mTc-F(ab')2 in quantitative yield and
      contaminated with 99mTc-Fab'. The properties, stability and biodistribution of
      the 99mTc-F(ab')2 have been compared to 99mTc-Fab'. This new technology will
      allow us to compare technetium direct-labeled IgG, F(ab')2 and Fab' derivatives
      of the same antibody for radioimmunodetection.

PMID- 9234324
TI  - Synthesis and evaluation of a new class of technetium-99m monocationic
      radiotracers from dithienyldiazalkanes.
AB  - Monocationic 99mTc complexes, [99mTcO2 (THEN)]+ and [99mTcO2(THPN)]+ derived from
      a new class of N2S2 chelators diethienyldiazalkanes, namely 1,6-di(2-thienyl)-2,5
      diazahexane (THEN) and 1,7-di- (2-thienyl)-4,4-dimethyl-2,6-diazaheptane (THPN),
      have been synthesized using Sn(II) tartrate reduction of [99mTc]pertechnetate at
      pH 9 and extraction of the complexes as ion pairs with trifluoromethane sulfonate
      anion (CF3SO3-) in high radiochemical yield (approximately 90%). Radiochemical
      analysis of the 99mTc complexes using chromatography (Whatman Cellulose CEL300
      DEAE anion exchange strip, MEK) and paper chromatography (Whatman I, acetone)
      revealed high radiochemical purity (> 90%). High octanol-saline partition
      coefficients (> 37) of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ indicated a
      lipophilic nature of the complexes. Relative stability of the 99mTc complex was
      high as measured by DTPA challenge studies. Biodistribution of [99mTcO2(THEN)]+
      and [99mTcO2(THPN)]+ in rats at 15 min post-injection showed heart-to-blood
      activity ratios of 0.26 and 0.46, respectively, with rapid blood clearance.
      Further studies involving the variation of substituents on the basic core
      structure of this new class of 99mTc complexes may provide radiotracers suitable
      for myocardial imaging.

PMID- 9234326
TI  - Synthesis of [11C]dapoxetine.HCl, a serotonin re-uptake inhibitor:
      biodistribution in rat and preliminary PET imaging in the monkey.
AB  - [11C]Dapoxetine.HCl, S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl]
      benzenemethanamine hydrochloride, a potent serotonin re-uptake inhibitor was
      prepared from its mono-methyl precursor, S-(+)-N-methyl-a-[2
      (naphthalenyloxy)ethyl]benzene methanamine hydrochloride. Biodistribution was
      determined in rats at 5, 30 and 60 min after injection and preliminary PET
      studies were performed in a Rhesus monkey. 11CH3I was bubbled into a solution of
      S-(+)-N-methyl-alpha-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride
      (3.0 mg in DMSO) and the mixture was heated at 110 degrees C for 8 min.
      [11C]Dapoxetine.HCl was purified by HPLC on a C18 cartridge eluted with
      MeOH:phosphate buffer, pH 7,2 (75:25) with a 10% yield (end of synthesis). The
      time required for the synthesis was 40 min, from the end of bombardment.
      Radiochemical purity of the final product was > 99% and specific activity was
      routinely > 400 mCi/mumol [EOS]. In the biodistribution studies the highest
      concentration (%ID/g +/- SEM) of dapoxetine.HCl was detected in lung: 4.56 +/-
      0.27 (5 min), 1.28 +/- 0.18 (30 min) and 0.67 +/- 0.04 (60 min). Brain
      accumulation was 0.76 +/- 0.02 (5 min), 0.46 +/- 0.04 (30 min) and 0.27 +/- 0.01
      (60 min). Preliminary PET studies demonstrated significant displaceable binding
      in the cerebral cortex and subcortical grey matter. These results demonstrate
      that [11C]dapoxetine.HCl can be prepared in high purity and may be useful for the
      in vivo evaluation of serotonin re-uptake mechanisms.

PMID- 9234325
TI  - Evaluation of 3-[18F]fluoro-alpha-fluoromethyl-p-tyrosine as a tracer for
      striatal tyrosine hydroxylase activity.
AB  - 3-[18F]Fluoro-alpha-fluoromethyl-p-tyrosine (3-F-FMPT) was evaluated as a tracer
      for CNS tyrosine hydroxylase (TH) activity in rodents and in a rhesus monkey.
      Results of in vitro experiments using rat striatal homogenates showed that the
      introduction of fluorine into the 3-phenyl position did not significantly alter
      the ability of FMPT to act as a TH-activated L-aromatic amino acid decarboxylase
      (L-AAAD) inhibitor. These studies further showed that 3-F-FMPT-induced L-AAAD
      inhibition was dose-dependent. Furthermore, striatal homogenates prepared from
      rats pretreated with the potent TH inhibitor alpha-methyl-p-tyrosine was found to
      have diminished 3-F-FMPT-induced L-AAAD inhibition. However, despite these
      promising in vitro results, the biodistribution of this compound in mice showed
      low brain uptake and fast clearance through the kidneys. A PET study using a
      Rhesus monkey injected with 3-[18F]F-FMPT confirmed the results obtained in mice,
      i.e. negligible brain uptake but high localization in the bladder. We conclude
      that 3-[18F]F-FMPT would not be useful as a tracer for cerebral TH activity.

PMID- 9234327
TI  - 48V radionuclidic impurity in product streams from liquid cyclotron targets with
      titanium windows.
AB  - Vanadium-48, a positron emitter with a 16.0 day half-life, was observed in the
      aqueous product stream from a liquid cyclotron target equipped with a titanium
      window, a type of target system commonly used for preparing [13N]NH3 at PET
      centers. The amount of 48V activity is directly related to bombardment time and
      beam current. It is apparently present as vanadate ion, and it is efficiently
      removed by anion exchange cartridges. More generally, it is likely that the
      specie would be present in the product stream of any titanium-window-equipped
      liquid target which contains water and which is bombarded with protons or
      deuterons. Incidental to the 48V investigation, was quantitation of 18F in the
      system under study.

PMID- 9234328
TI  - The distribution of [11C]cocaine in normal and cocaine-sensitization mice.
AB  - [N-11C-methyl]-cocaine ([11C]cocaine), synthesized by N-methylation of norcocaine
      with [11C]CH3I, was used to assist in imaging the variety of local distribution
      by positron emission tomography (PET). The radiochemical yield and the
      radiochemical purity after purification of [11C]cocaine by high performance
      liquid chromatography (HPLC) at a sp. act. of 814 GBq/mmol were 47-58% and > 99%,
      respectively. The time required for synthesis including the purification was 25
      30 min from the end of [11C]CH3I trapping. The physical distribution of
      [11C]cocaine in organ was also investigated in mice at various time after i.v.
      injection. The main accumulation of radioactivity occurred in the lung, kidney
      and brain within 1 min after the injection. In the brain, no differences in the
      organ were observed except the radioactivity level in each section increased for
      the first 5 min, since then radioactivity decreased dramatically. Furthermore, in
      the behavioral sensitization model of cocaine, the peak of [11C]cocaine uptake in
      each brain area was shown to be 5-15 min.

PMID- 9234329
TI  - Design and evaluation of radioactive acetylcholine analogs for mapping brain
      acetylcholinesterase (AchE) in vivo.
AB  - For mapping brain acetylcholinesterase (AchE) in vivo, seven radioactive
      acetylcholine analogs, N-[14C]methylpiperidyl-3- and 4-acetates, propionates,
      isobutyrates, and 3-butyrate were newly synthesized and evaluated in mice. The
      esters readily entered the brain and were hydrolyzed into the hydrophilic
      metabolite, which was trapped. In brain homogenates, the esters showed a wide
      range of enzymatic reactivity (about 40-fold), and high specificity for AchE
      (more than 82%) except the butyrate. Intra-brain distribution of the esters
      reflected a pattern of AchE activity.

PMID- 9234330
TI  - 8-[18F]fluorooctanoic acid and its beta-substituted derivatives as potential
      agents for cerebral fatty acid studies: synthesis and biodistribution.
AB  - Fluorine-18 labeled analogs of 8-fluorooctanoic acid and its structurally
      modified derivatives with methyl or gem-dimethyl branching or with oxygen
      substitution at the C3 position were prepared using nucleophilic substitution of
      the tosylate precursors by [18F]fluoride ion, for evaluation as tracers for
      cerebral fatty acid metabolism. Tissue distribution studies in rats showed low
      brain uptakes of these 18F-labeled fatty acid analogs with poor brain-to-blood
      ratios of activity. The oxygen-substituted analog did not show any significant
      accumulation of radioactivity in most tissues. The initial brain uptake of
      activity after injection of ethyl 8-[18F]fluorooctanoate and its free acid
      remained virtually unchanged over an extended time period, beta-Monomethyl and
      beta-gem-dimethyl branched analogs had similar brain uptake at the early time
      period, but they showed rapid clearance of activity from the brain. TLC analysis
      showed no incorporation of 8-[18F]fluorooctanoic acid and its beta-dimethyl
      analogs into brain lipids. It was also shown in the metabolite analysis that the
      labeled metabolites produced from 8-[18F]fluorooctanoic acid are found in blood,
      and that they could enter the brain to a significant degree. On the contrary,
      such radioactive metabolites could not be found in the brain in the experiment
      with the beta-gem-dimethyl branched analog. Thus, the present studies showed that
      retention of radioactivity in the brain with 8-[18F]fluorooctanoic acid
      derivatives is mainly attributable to their radioactive metabolites, and that the
      rapid clearance of beta-branched analogs from the brain is due to the lack of
      availability as substrates in the cerebral fatty acid metabolism.

PMID- 9234331
TI  - (2-[18F]fluoropropionyl-(D)phe1)-octreotide, a potential radiopharmaceutical for
      quantitative somatostatin receptor imaging with PET: synthesis, radiolabeling, in
      vitro validation and biodistribution in mice.
AB  - Octreotide is labeled with fluorine-18 as a potential radiopharmaceutical for
      quantitative in vivo mapping of somatostatin receptors. [18F]-fluoroacylation is
      achieved with n.c.a. 2-[18F]fluoropropionic acid 4-nitrophenylester which is
      reacted with epsilon-Boc-Lys5-octreotide. After deprotection the desired N alpha
      [18F]fluoropropionylated octreotide ([18F]SDZ 223-228) is obtained. Final HPLC
      purification gives rise to radiochemical yields of 65 +/- 5% based on the
      fluoroacylation agent. Binding experiments using rat cortex membranes indicate an
      affinity for somatostatin receptors of pKi = 8.6 +/- 0.2. The biological activity
      of this SRIF analog is demonstrated by the inhibition of growth hormone release
      from cultured pituitary cells. The pIC50 in this test system is 8.75, indicating
      full biological activity. Biodistribution studies with NMRI mice show
      predominantly renal excretion, rapid blood clearance and only negligible bone
      activity, i.e. formation of free fluoride.

PMID- 9234332
TI  - FDG uptake, tumor proliferation and expression of glycolysis associated genes in
      animal tumor models.
AB  - To determine the influence of tumor cell proliferation and changes in the genetic
      program in malignant cells on the fluorodeoxyglucose (FDG) uptake we performed
      PET studies in several animal tumors: spontaneous mammary fibroadenoma,
      chemically-induced mammary adenocarcinoma and Dunning prostate adenocarcinoma.
      The expression of the glucose transporter (GLUT1) and of hexokinase (Hk) was
      measured using 32P-labeled cDNA probes and densitometry. Furthermore the
      proliferative activity was determined with one-dimensional flow cytometry. The
      FDG uptake and the proliferation parameters were not correlated. The normalized
      amounts of GLUT and Hk mRNA were lower in spontaneous fibroadenomas and prostate
      tumors than in chemically induced mammary. The FDG uptake was correlated to GLUT1
      expression with r = 0.83 and to Hk expression with r = 0.77. Multiple regression
      analysis revealed a relation of FDG uptake to GLUT1 and HK with r = 0.87. Our
      results show that the FDG uptake in our study was related not to differences in
      proliferation, but rather to differences in the transcription of glycolysis
      associated genes.

PMID- 9234334
TI  - First-pass extraction fraction of iodine-123 labeled perfusion tracers in living
      primate brain.
AB  - The cerebral extraction and retention of three radioiodinated SPECT perfusion
      tracers were measured using residue detection in a baboon. A permeability-surface
      area product PS' with special relevance to SPECT was calculated from the
      retention of tracer in the brain after 10 min. PS' differs from the traditional
      PS value, which is calculated from the tracer clearance curve at 2 min. The PS'
      values ranged from 50 to 95 mL/min/100 g, decreased in the order [123I]IMP >
      [123I]iodoperidol approximately [123I]HIPDM, and did not differ for specific
      activities of 10 MBq/mmol to 74 TBq/mmol. These radioiodinated compounds
      exhibited extraction characteristics superior to those of [99mTc]HMPAO but
      underestimated cerebral blood flow when flows were above 20-30 mL/min/100 g,
      underscoring the need for development of a more ideal SPECT perfusion tracer.

PMID- 9234333
TI  - Metabolic and transcriptional changes in osteosarcoma cells treated with
      chemotherapeutic drugs.
AB  - Two cell lines derived from a lung metastasis of a rat osteosarcoma were treated
      with cisplatin (CDDP) and two phosphonic acid compounds (AMDP, DADP), AMDP
      treated cells showed a decrease in FDG uptake, CDDP and DADP resulted in an
      increase. A block in G2 or in S and G2 phase was seen after CDDP and AMDP
      treatment. The changes in the cell cycle fractions were not related to the
      changes in FDG uptake. Furthermore, the transcription of the glucose transporter
      and hexokinase genes were elevated in CDDP and decreased in AMDP treated cells.
      However, the changes in FDG uptake were not fully explained by changes at the
      transcriptional level. The total uptake of thymidine was elevated although the
      incorporation of thymidine into DNA decreased. In both cell lines the changes in
      FDG uptake correlated with the changes in thymidine incorporation into DNA (r =
      0.95 and r = 0.83, respectively). Cells with an increased FDG uptake showed a
      weaker growth inhibition than cells with a decrease in FDG uptake.

PMID- 9234335
TI  - A kinetic comparison of [18F]2-fluoro-2-deoxyglucose and [18F]2-fluoro-2
      deoxymannose using positron emission tomography.
AB  - Rate constants and fractional metabolic rates were estimated for the
      stereoisomers [18F]2-fluoro-2-deoxyglucose (FDG) and [18F]2-fluoro-2-deoxymannose
      (FDM) in 5 male baboons using positron emission tomography. Each animal, serving
      as its own control, was injected with both compounds under controlled
      physiological conditions. Results indicate that there is a 20% reduction in
      apparent cerebral metabolic rates for glucose when FDM is used as the analogue.
      This suggests that as supplies of 18O become depleted, the presence of FDM as an
      impurity should warrant consideration in the choice of alternatives to no-carrier
      added FDG synthesis.

PMID- 9234336
TI  - In vivo dynamical distribution of 131I-VIP in the rat studied by gamma-camera.
AB  - The in vivo distribution of vasoactive intestinal peptide (VIP) was studied for
      the first time using a rat model in combination with labeled VIP (131I-VIP) and a
      gamma-camera. A dynamic scan showed that 131I-VIP was cleared rapidly from the
      blood circulation. The radioactivity was taken up and accumulated in the lungs
      during the first minute. During the next 15 min, the radioactivity was slowly
      removed from the lungs and redistributed into the kidneys, gastric mucosa, liver
      and small intestine. However, the radioactivity extracted by the lungs was about
      6-fold lower during the first minute when a large amount of the non iodinated VIP
      was coinjected with the 131I-VIP. 131I-VIP was eliminated rapidly from the blood
      with a half-life of 0.44 +/- 0.05 (min +/- SD) while in lung the elimination half
      life was determined to 2.3 +/- 0.8 (min +/- SD). Of the radioactivity in the
      lungs, 2% was found to be intact 131I-VIP after 20 min. In all other organs the
      radioactivity found was assumed to be low molecular weight fragments of 131I-VIP.
      We suggest that lungs play an important role to extract VIP from the circulation
      after an i.v. administration. 131I-VIP degradation products are redistributed
      mostly to the kidneys and to the gastric mucosa to be excreted through urine and
      stomach contents, respectively.

PMID- 9234337
TI  - Immunoreactivity, stability, pharmacokinetics and biodistribution of a monoclonal
      antibody to human leukemic B cells after three different methods of
      radioiodination.
AB  - Dal B02, a murine monoclonal antibody against human chronic lymphocytic leukemia
      (CLL) was radioiodinated using chloramine T (Chl.T), Bolton-Hunter (B-H) or N
      succinimidyl-p-iodobenzoate (PIB). The preparations had comparable radiochemical
      purity (> 97%) and immunoreactive fraction (65-80%) but the Chl.T-based product
      was most susceptible to deiodination and loss of immunoreactivity. After i.v.
      injection into CLL-xenografted nude mice, the preparations had identical patterns
      of clearance from the blood but the PIB-based product led to more radioactivity
      in liver and spleen and less in the thyroid compared to the other preparations.
      The Chl.T-based product showed loss of immunoreactivity in circulation and less
      tumor-localized radioactivity 168 h after administration. The differences between
      the B-H-based and PIB-based products were less impressive than between PIB-based
      and Chl.T-based products.

PMID- 9234338
TI  - Assessment of left ventricular regional function by radionuclide angiography:
      effects of number of sectors on repeatability.
AB  - Twenty patients were studied by equilibrium radionuclide angiography (RNA) twice
      in the same day in order to assess the repeatability of quantitative measurements
      of left ventricular (LV) regional function by using a sector analysis method. RNA
      was performed in the best septal 45 degrees left anterior oblique projection,
      acquiring 150,000 counts/frame, at 20 msec/frame with 5% gate tolerance. LV
      regional analysis was performed using a computer algorithm written by the authors
      running on Digital PDP 11/34 machine. The algorithm after having identified the
      center of gravity of the LV, divided it into 4, 5 and 6 equiangular sectors. In
      the 5, and 6 sector analysis, the region including the mitral and aortic valves
      was excluded from subsequent analysis. In each sector Ejection Fraction (EF) and
      Peak Filling Rate (PFR) were computed. In addition, the Time to End Systole (TES)
      and Time to Peak Filling Rate were also assessed for each region. The coefficient
      of variation of the regional values of TES (CV-TES) and regional TPFR (CV-TPFR)
      were then computed and considered as indices of LV systolic (CV-TES) and
      diastolic (CV-TPFR) asynchrony. Repeatability was firstly assessed by linear
      regression analysis between the 2 RNA studies. Our data show a high correlation
      coefficient on regional values of EF and PFR (R: > 0.92). Moreover, the
      differences in a given parameter between the 2 studies were plotted against their
      mean value, and the coefficient of repeatability (CR) was calculated as twice the
      standard deviation of the differences. No significant differences were found
      between EF and PFR regional values in the 2 RNA studies (EF coefficient of
      repeatability: < 0.18; PFR coefficient of repeatability: < 0.8). A low value of
      coefficient of repeatability was found also for CV-TES (< 17) and for CV-TPFR (<
      18). In conclusion LV regional analysis is a repeatable method of analysis, and
      the number of regions does not affect the repeatability.

PMID- 9234339
TI  - Effect of systemic DTPA treatment on tissue retention of free and carrier-bound
      111In from labelled proteins and polymer.

PMID- 9234340
TI  - Leukocyte labeling with 99mTc-HMPAO. The role of the in vitro stability of HMPAO
      on the labeling efficacy and image quality.

PMID- 9234341
TI  - Rapid synthesis and quality control of 68Ga-labeled chelates for clinical use.

PMID- 9234342
TI  - A new radioiodinated agent for detecting radicals in vivo: synthesis and
      preliminary evaluations.

PMID- 9234343
TI  - Evaluation of 153Sm-diethylenetriaminepentaacetic acid for radiolabelling of
      pharmaceutical dosage forms by neutron activation.
AB  - 153Sm-DTPA provides a suitable alternative to 99mTc-DTPA and 111In-DTPA as a
      water soluble tracer for the evaluation of pharmaceutical preparations. The
      chelate was handled biologically in a similar way to 99mTc-DTPA and 111In-DTPA.
      The chelate can be incorporated into the formulation as a non-radioactive
      excipient and the intact dosage form can then be neutron activated to produce
      153Sm.

PMID- 9234344
TI  - Preclinical evaluation and PET imaging of 18F-labeled Mel-14 F(ab')2 fragment in
      normal dogs.
AB  - The F(ab')2 fragment of monoclonal antibody Mel-14, reactive with human melanomas
      and gliomas, was labeled with 18F using two acylation agents, N-succinimidyl 8
      [(4'-[18F]fluorobenzyl)amino]suberate (SFBS) and N-succinimidyl 4
      [18F]fluorobenzoate (SFB). The immunoreactivity and affinity for Mel-14 F(ab')2
      labeled using the two methods were similar. As a prelude to human clinical
      evaluation, PET imaging, tissue distribution and pharmacokinetic measurements
      were performed in two groups of normal foxhounds. Similar in vivo behavior was
      seen for Mel-14 F(ab')2 labeled using SFBS and SFB. Radiation dosimetry
      calculations suggest that a 10 mCi dose could be used for this F(ab')2 fragment
      labeled using either acylation agent.

PMID- 9234345
TI  - Synthesis of n.c.a. carbon-11 labelled clozapine and its major metabolite
      clozapine-N-oxide and comparison of their biodistribution in mice.
AB  - N.c.a. [11C]clozapine, [8-chloro-11-(4-[methyl-11C]-methyl-1-piperazinyl)-5H
      dibenzo[b,e]-1, 4-diazepine], 1, an atypical neuroleptic was synthesized by N
      methylation of the desmethyl compound norclozapine, 3, using [11C]methyl iodide
      or [11C]methyl triflate for comparison. Subsequent oxidation of 1 with m
      chloroperoxybenzoic acid yielded clozapine-N-oxide, 2, the major metabolite of 1.
      Purification of both radiolabelled products was carried out using a combined semi
      preparative HPLC/solid phase extraction procedure. In preparative scale runs
      overall radiochemical yields for 1 and 2 were 70 and 65%, respectively. The
      radiochemical purities of both compounds exceeded 98% and the specific activities
      were in the range of 92-130 GBq/mumol (2.5-3.5 Ci/mumol). Biodistribution of 1
      and 2 has been studied in NMRI mice. 10 min p.i. clozapine shows a 24-fold higher
      brain uptake than its major metabolite. At 60 min p.i., however, the cerebral
      uptake of both compounds is almost identical.

PMID- 9234346
TI  - Brain kinetics of (R)- and (S)-[N-methyl-11C]ketamine in the rhesus monkey
      studied by positron emission tomography (PET).
AB  - The regional brain kinetics of the two enantiomers of the NMDA channel blocker
      ketamine radiolabelled with 11C was studied in the Rhesus monkey by means of
      positron emission tomography (PET). The uptake in brain areas which showed high
      radioactivities was blocked in a dose-dependent manner for both 11C-labelled
      enantiomers with simultaneous doses of the respective unlabelled (S)- or (R)
      ketamine, indicating specific binding. The binding in the striatum and cortical
      areas of (S)-[N-methyl-11C]ketamine was selective and displaceable by the (R)
      enantiomer and by MK-801.

PMID- 9234347
TI  - Application of high affinity binding concept to radiolabel avidin with Tc-99m
      labeled biotin and the effect of pI on biodistribution.
AB  - In order to label avidin with Tc-99m, we took advantage of the high affinity
      binding of biotin to avidin; we radiolabeled a biotin derivative with Tc-99m and
      then bound this Tc-99m labeled biotin derivative to avidin. For our labeling
      approach, N epsilon-biotinyl-L-lysine (Biocytin) was reacted with the N-hydroxy
      succinimide ester of benzoylmercaptoacetyltriglycine (Bz-MAG3). The resulting Bz
      MAG3-Biocytin was labeled with Tc-99m using Tc-99m glucarate as a Tc-99m
      transchelating agent and mixed with avidin at a 1:1 molar ratio resulting in
      almost a quantitative labeling yield. Tc-99m-MAG3-Biocytin/Avidin was stable in
      serum at 37 degrees C with 97 and 95% of the total Tc-99m activity still bound to
      avidin at 2 and 24 h, respectively. The biodistribution of Tc-99m-MAG3
      Biocytin/Avidin in normal Balb/c mice showed a high liver and kidney uptake with
      56.6 and 28.9%, respectively at 10 min. We attempted to lower the liver and the
      kidney activities by reducing the isoelectric point (pI) of avidin by conjugating
      succinic acid moieties at lysine residues of avidin (pI 10). The kidney uptake
      decreased to 19.0, 3.1 and 1.7% when the pI of avidin was reduced to 7.0-9.3, 5.5
      6.2 and 4.0-4.8, respectively. The lowering of the pI, however, did not change
      the liver activity appreciably.

PMID- 9234348
TI  - Metabolism of a [18F]fluorine labeled progestin (21-[18F]fluoro-16 alpha-ethyl-19
      norprogesterone) in humans: a clue for future investigations.
AB  - Assessment of estrogen receptors and progesterone receptors (PR) with PET may
      allow the determination of the hormone responsiveness of tumors without the need
      for multiple biopsies, and the monitoring of the effect of hormonal therapy. In
      spite of the favourable characteristics of 21-[18F]fluoro-16 alpha-ethyl-19
      norprogesterone ([18F]FENP) found in preclinical studies, the compound failed to
      reveal the presence of PR in breast carcinomas and meningiomas. In view of the
      clinical significance of the PR assay in human breast cancer, it is worthwhile to
      explore mechanisms that are potentially involved in the inadequacy of [18F]FENP
      to image PR with PET. Our present study on the in vivo metabolism of [18F]FENP in
      humans demonstrates a rapid clearance and biotransformation of the compound.
      Results of incubation experiments suggest that the metabolic conversion of
      [18F]FENP is not restricted to the liver, but also occurs in blood cells
      (presumably the erythrocytes) and tumors (breast carcinomas and meningiomas). The
      predominant metabolite of [18F]FENP in plasma during the rapid distribution phase
      and in tumors is identified as 20-dihydro-[18F]FENP. The conversion of [18F]FENP
      to its 20 alpha- or 20 beta-hydroxy metabolite has a deleterious effect on the
      binding affinity for PR. Our findings do not justify a conclusion as to the
      extent of in vivo extrahepatic biotransformation of [18F]FENP, or its
      significance in the ineffectiveness of [18F]FENP as an imaging agent for PR. On
      the other hand, the ability of breast carcinomas and meningiomas to metabolize
      [18F]FENP avidly appears to preclude selective imaging of PR in these tumors
      during the time of a PET examination. It is imperative to evaluate the metabolic
      stability of a [18F]fluorine labeled progestin in an early stage of future
      screening procedures.

PMID- 9234349
TI  - Determination of the target volume of HeLa cells treated with platinum-195 m
      radiolabeled cis-diammine(1, 1-cyclobutane-dicarboxylato)-platinum(II);
      comparison with cis- and trans-diamminedichloroplatinums(II).
AB  - HeLa S-3 cells were treated with 195mPt-radiolabeled cis-diammine(1, 1
      cyclobutane-dicarboxylato)platinum(II) (carboplatin) under various conditions,
      and the relationship between lethal effect and the number of Pt atoms binding to
      DNA, RNA and proteins was examined. The mean lethal concentrations for the cells
      treated with carboplatin at 37 degrees C for 1, 2 and 3 h were 553.4, 194.3 and
      68.7 microM, respectively. By using identically treated cells, the numbers of Pt
      atoms combined with DNA, RNA and protein molecules were determined after
      fractionation of the cells. In this way the D0 values (D0, dose that would give
      an average of one lethal event per member of the population), expressed as the
      drug concentration, were substituted for the number of Pt atoms combined with
      each fraction. The target volumes, the efficiency of Pt atom to kill cells
      expressed as the reciprocals of the D0 values, were then calculated with each
      fraction. The results suggested that DNA was the primary target for cell killing
      by carboplatin. The target volumes for DNA were 0.891 x 10(4), 2.01 x 10(4) and
      3.96 x 10(4) nucleotides for 1, 2 and 3 h treated cells, respectively. The cell
      killing effects of carboplatin were lower than those of cis
      diamminedichloroplatinum(II) (CDDP) by factors of 6.0, 2.8 and 2.6 for 1, 2 and 3
      h treatments at 37 degrees C, respectively, in terms of the target volume, while
      those in terms of the mean lethal dose (D0) were 59.5, 29.0 and 21.5,
      respectively.

PMID- 9234350
TI  - Does the anabolic metabolism of L-[2-18F]fluorophenylalanine and L-[2,6
      3H]phenylalanine differ in the cerebrum and the cerebellum?
AB  - The anabolism of isotopically labeled amino acids was compared between the
      cerebrum and the cerebellum in conscious rat at three feeding conditions. After L
      [2-18F]fluorophenylalanine and L-[2,6-3H]phenylalanine injections, the
      incorporation rate of both radioactivity into protein fraction showed no
      difference between the cerebrum and the cerebellum at normal condition, but the
      lipid fraction in the cerebellum was higher than that in the cerebrum in any
      conditions. These results show the usefulness of L-[2-18F]fluorophenylalanine as
      a positron emission tomography tracer and different anabolic rate of the amino
      acids to lipid between the cerebrum and cerebellum.

PMID- 9234351
TI  - Procedure for red blood cell labelling with 99mTc-HMPAO. Methodology and quality
      control.
AB  - We present here results on the labelling of red blood cells with 99mTc-HMPAO as
      an alternative method to the usual in vitro technique. Anticoagulant agents, the
      labelling medium with plasma, and the lapse of time between 99mTc-HMPAO
      preparation and labelling are the main factors which affect the efficiency of the
      procedure. A 93.9 +/- 2.3% labelling yield was obtained with freshly prepared
      99mTc-HMPAO. In vitro (tracer elution of 4.3 +/- 1.2% at 60 mins) and in vivo
      (percentage of plasma activity at 60 mins, 7.8 +/- 2.8%) stability of the label,
      as well as image quality, qualify 99mTc-HMPAO labelled red blood cells as a
      suitable agent for clinical use.

PMID- 9234352
TI  - Pharmacokinetics of the three radioiodinated dopamine D2 receptor ligands
      [123I]IBF, [123I]epidepride and [123I]2'-ISP in nonhuman primates.
AB  - The pharmacokinetics of three radioiodinated high affinity dopamine D2 receptor
      binding ligands-two benzamide neuroleptics (IBF and epidepride) and the
      butyrophenone neuroleptic analog 2'-iodospiperone (2'-ISP)-were measured in
      nonhuman primates. [123I]IBF and [123I]epidepride were prepared by
      iododestannylation of the corresponding tributylstannyl derivative, whereas
      [123I]2'-ISP was labeled by (NH4)2SO4 mediated iodide for bromide exchange
      starting from 2'-bromospiperone. Labeled products were purified by HPLC and were
      obtained in > 93% radiochemical purity and > 7000 Ci/mmol sp. act. After i.v.
      injection in baboons, serial arterial plasma samples were extracted with ethyl
      acetate (IBF and epidepride) or denatured with methanol (2'-ISP) and analyzed by
      HPLC. For IBF, plasma levels of parent compound dropped to 50% of the plasma
      activity within 20 min post injection and the major radiometabolite was
      lipophilic. For epidepride, it took 30-40 min for parent content to reach 50% and
      the major radiometabolite was polar. For 2'-ISP, parent composition dropped to
      60% after about 15 min. Arterial input curves for IBF and epidepride fit three
      exponential models with terminal half-life of 54-76 and 50-59 min, respectively.
      Whole body images were acquired using the conjugate counting method. The
      distribution of all three agents was qualitatively similar, with major excretion
      through the hepatobiliary route. Peak whole brain uptake, observed within 20 min
      for all three tracers, was estimated as 7% injected dose for [123I]IBF, 8% for
      [123I]epidepride and 5% for [123I]2'-ISP.

PMID- 9234353
TI  - A windowless 13N production target for use with low energy deuteron accelerators.
AB  - The recent development of low energy accelerators for positron emission
      tomography has necessitated the development of new targets for 13N production.
      12C(d,n)13N reaction yields in graphite at low deuteron beam energies (0.8-3.2
      MeV) are presented and a new technique for the in situ extraction of 13N activity
      from solid graphite and subsequent conversion to [13N] ammonia is described. The
      target is windowless and is reusable for multiple isotope production runs. This
      technique utilizes radio frequency induction heating to rapidly heat the graphite
      to combustion temperatures in an O2 gas stream. The conversion of activity
      induced in the target to [13N] ammonia in under 10 min with an overall decay
      corrected efficiency of 45% is reported.

PMID- 9234354
TI  - Production of [13N]ammonia applicable to low energy accelerators.
AB  - We have developed a technique for the rapid conversion of the nitrogen-13 induced
      in a graphite target into nitrogen oxides. This was accomplished by heating the
      graphite target in a stream of pure oxygen at 800 degrees C. Less than 20% of the
      radioactivity was found in the form of [13N]nitrogen. The rest of the
      radioactivity was efficiently trapped in a solid-phase medium that consisted of
      an aqueous solution of 5% NaOH dispersed in silica gel. The radioactivity from
      this solid-phase medium was eluted with water (94% recovery) and found to be in
      the form of 13NO2- (99%). This was subsequently converted to [13N]ammonia with
      Raney-nickel, either by a conventional liquid-phase reduction with an overall
      conversion efficiency to ammonia of 45%, or by an incorporation of the Raney
      nickel into the solid-phase medium. The latter system resulted in an overall
      conversion efficiency to ammonia of 37 +/- 9%, with a radiochemical purity of
      nearly 100% and a synthesis time under 17 min.

PMID- 9234355
TI  - Some observations on the instability of 99mTc-complexes of propylene amine oxime
      (PnAO).
AB  - When eluates from expired 99mMo/99mTc generators were used to form the neutral
      lipophilic complexes of PnAO and its derivatives, degradation of these chelates
      occurred on standing to form secondary 99mTc-species. It was determined that the
      conversion of the primary complexes to secondary complexes was due to the
      impurities present in the 99mTcO4- eluate. The stability was found to be improved
      by extraction of the complexes into CHCl3 and reconstituting in buffer after
      evaporation of CHCl3, indicating that the impurities are non extractable into
      CHCl3. Purification of the 99mTcO4- eluate from the generator by MEK extraction
      and its use for the preparation of the PnAO complex produced products which
      showed practically no degradation for a 6 h period of storage. All the secondary
      99mTc complexes of PnAO are converted back to primary complex, when the solution
      was heated in a boiling water bath for 10-20 min.

PMID- 9234356
TI  - The use of pentafluorophenyl derivatives for the 18F labelling of proteins.
AB  - A simple, one-step method for the radiolabelling of proteins with 18F is
      described. A series of pentafluorophenyl derivatives were synthesized and tested
      for 18F exchange using tetrabutylammonium-[18F]fluoride in DMSO, with microwave
      heating. A number of the compounds examined incorporated 18F quickly and in high
      yield. Two compounds, pentafluorobenzaldehyde and 2,3,5,6
      tetrafluorophenylpentafluorobenzoate, were used to label HSA in good yield. The
      methods produce low specific activity labelled proteins, but are fast. The yields
      are reasonable and the reagents do not require a separate modification or
      activation step for protein labelling.

PMID- 9234357
TI  - Modified radioiodination and quality control methods for [125I]sodium
      iothalamate.
AB  - [125I]Sodium iothalamate can be prepared by the isotope-exchange method with the
      use of a contrast medium preparation (i.e. iothalamate sodium injection, USP,
      80%). The initial isolation and purification of iothalamate from the contrast
      medium solution for radioiodination is tedious and time-consuming (i.e. 1 1/2 h
      for purification and overnight for drying). The new method uses iothalamic acid
      to replace iothalamate sodium injection as a starting material and reduces the
      heating time and multiple acid-washing steps during radioiodination to expedite
      the radiolabelling process. The radiochemical purity (RCP) of [125I]sodium
      iothalamate obtained from the new method was 98.9 +/- 1.3% (n = 30) versus RCP
      value of 99.2 +/- 1.0% (n = 25) from the old method with no significant
      differences between the two groups of RCP values. An RCP chromatographical system
      to separate and migrate the radiochemical species of [125I]sodium iothalamate
      from the origin is described in this paper.

PMID- 9234358
TI  - A freeze dried kit formulation for the preparation of 99mTc-EHDP-MoAb-IOR CEA1
      complex.
AB  - A freeze dried kit formulation for the preparation of 99mTc-labelled IOR-CEA1, a
      monoclonal antibody (MoAb) against a human colorectal cancer, was developed.
      Methods of analysis were also established permitting identification of
      radiochemical impurities which may be present in radiopharmaceutical solution.
      99mTc-EHDP-MoAb-IOR CEA1 prepared by the kit method was evaluated in human
      volunteers to apply the radioimmunodetection of human colon cancer. Data
      demonstrated that the complex formed after kit-reconstitution shows excellent
      stability and tumor seeking properties. Colon carcinoma in patients was
      successfully detected 6-8 and 20-28 h post administration.

PMID- 9234359
TI  - 125I-labelling of an internally 75Se-labelled monoclonal antibody-
      biodistribution in tumour-bearing nude mice.
AB  - A monoclonal antibody, C215, was first internally labelled with 75Se-methionine
      and then labelled with 125I. The biodistribution of the dual-labelled
      [125I][75Se]C215 was studied in tumour-bearing nude mice killed 3 days after
      injection. The biodistribution of the dual-labelled [125I][75Se]C215 was compared
      with the biodistribution of single-labelled [131I]C215 and [75Se]C215. Iodine
      labelled antibodies seem to be damaged during iodination, affecting the
      disappearance rate and tumour uptake. There were no signs of dehalogenation of
      circulating antibodies or antibodies taken up in the tumour.

PMID- 9234360
TI  - Metabolism of receptor targeted 111In-DTPA-glycoproteins: identification of 111In
      DTPA-epsilon-lysine as the primary metabolic and excretory product.
AB  - The hepatic and renal retention of indium-111 (111In) from 111In-labeled
      polypeptides has been the subject of many investigations. Because the lysosome is
      a common intracellular destination for the degradation of polypeptides, we
      studied the lysosomal metabolism of 111In-DTPA-labeled glycoproteins targeted to
      cell surface receptors in vitro and in vivo. We found that 111In-DTPA
      glycoproteins were degraded to 111In-DTPA-epsilon-lysine, which was slowly
      released from cells and recovered intact in urine and feces. These results
      suggest a mechanism for 111In retention at target and non-target sites.

PMID- 9234361
TI  - Can a cysteine challenge assay predict the in vivo behavior of 99mTc-labeled
      antibodies?
AB  - Recent investigations have shown that transchelation to cysteine in a principal
      mode of in vivo instability of 99mTc-labeled antibodies. In this investigation, a
      cysteine challenge assay was used to measure the in vitro instability of 99mTc
      directly labeled to two IgG antibodies (B72.3 and C110) via two established
      direct labeling methods employing mercaptoethanol and stannous ion for antibody
      reduction and by a novel method using glutathione for this purpose. For both
      antibodies, the greatest instability to cysteine occurred with stannous ion
      reduction. The stability of glutathione-reduced B72.3 was indistinguishable from
      mercaptoethanol-reduced B72.3 whereas glutathione-reduced C110 showed stability
      roughly intermediate between that of the other reducing agents for this antibody.
      Results obtained in normal mice were in the direction predicted by the assay: for
      both antibodies, urinary clearance of 99mTc was fastest in mice receiving
      antibodies labeled via stannous ion reduction, presumably because of the
      increased transchelation of label to cysteine in vivo. Urinary clearance was
      slower and identical in mice receiving B72.3 labeled via glutathione or
      mercaptoethanol whereas clearance in the case of glutathione-reduced C110 was
      intermediate between that of the other two reducing agents. At both time points,
      higher radioactivity levels were observed in kidneys and lower levels in blood
      and most other tissues for both antibodies in the case of stannous ion reduction
      as expected for the label of greatest instability. In the B72.3 case, with only
      one exception, tissue and blood levels following administration of glutathione
      reduced antibody were indistinguishable from that following administration of
      mercaptoethanol-reduced antibody. In the C110 case, significant differences in
      activity levels were observed in several tissues between glutathione- and
      mercaptoethanol-reduced antibodies. In conclusion, the relative in vivo behaviour
      of 99mTc when administered to mice while labeled to two IgG antibodies were
      successfully predicted based on the results of an in vitro cysteine challenge
      assay.

PMID- 9234362
TI  - High performance liquid chromatography of carbon-11 labeled thymidine and its
      major catabolites for clinical PET studies.
AB  - The identity and pharmacology of the rapidly formed radiolabeled metabolites
      formed following i.v. injection of C-11 thymidine (TdR) labeled in the 5-methyl
      position are being studied in animal models and patients with cancer. A high
      performance liquid chromatographic (HPLC) procedure has been developed for the
      separation of these metabolites including thymine, dihydrothymine, beta
      ureidoisobutyric acid, and beta-aminoisobutyric acid from plasma and tissue
      extracts. Information obtained regarding the pharmacokinetics of the metabolites
      are being used to generate mathematical models for C-11 TdR incorporation rates
      into DNA.

PMID- 9234363
TI  - Synthesis of fatty acids specifically labelled with 11C in various positions,
      including 2H substitution, for in vivo studies of myocardium using PET.
AB  - Fatty acids were labelled with 11C in several positions by reacting [11C]carbon
      dioxide with the appropriate Grignard reagent or by reacting a alpha, omega-bis
      (bromo magnesium) alkane with a 11C-labelled alkyl iodide followed by a reaction
      with carbon dioxide. The methyl and methylene 11C-labelled fatty acids were
      obtained in 12-36% (decay corrected) radiochemical yield within 45-65 min, and
      with radiochemical purities higher than 96%. Perdeuterated alpha, omega-dibromo
      hexane, decane and tetradecane were synthesized from dimethylacetylene
      dicarboxylate by means of a Raney-nickel reduction in D2O, Kolbe electrolysis and
      LAD reduction. The use of multiple isotopic labelling by the combination of
      position specific 11C labelling and 2H substitution, has the potential to
      highlight different aspects of a complex biochemical system by PET. This
      principle is illustrated by results of the kinetics of different types of 11C
      label of dodecanoic acid and the corresponding moieties of acetate. The
      combination of tracers allows the kinetics of beta-oxidation of middle length
      carbon chain fatty acids and citric acid cycle metabolism to be separately
      assured, whilst deuteration of the tracers opens the possibility of highlighting
      the kinetics of the proton extraction processes reflecting rate limiting steps.

PMID- 9234364
TI  - Synthesis of [1-11C], [2-11C], [1-11C](2H3) and [2-11C](2H3)acetate for in vivo
      studies of myocardium using PET.
AB  - Four isotopically-labelled acetates ([1-11C], [2-11C], [1-11C](2H3) and [2
      11C](2H3)acetate) were synthesized and used in positron emission tomography (PET)
      studies of pig myocardium. The [1-11C]acetates were synthesized by carboxylation
      of the appropriate 1H or 2H methyl Grignard reagents immobilized on a C2 solid
      phase extraction column (SPE). Purification by reverse-phase HPLC, resulted in 35
      45% decay-corrected radiochemical yield with a total synthesis time of 25 min,
      and a radiochemical purity higher than 99%. The [2-11C]acetates were synthesized
      by carboxylation of 11C-labelled 1H or 2H methyl lithium. Purification as above
      resulted in 35-55% decay-corrected radiochemical yield with a total synthesis
      time of 30 min, and a radiochemical purity higher than 99%. Position-specific
      labelling was assessed by 13C-labelling and NMR. Multiple isotopic labelling by
      the combination of position-specific 11C-labelling and 2H substitution, has the
      potential to highlight different aspects of a complex biochemical system using a
      selected set of tracers in comparative PET studies. An illustration of this
      principle is given using acetate, where citric acid cycle metabolism results in a
      position-specific kinetic for the 11C-label, and deuteration opens up the
      possibility for the proton-abstracting processes within the citric acid cycle to
      be assessed.

PMID- 9234365
TI  - New renal function imaging agents. I. Synthesis and biological characterization
      of a [99mTc]diaminomercapto(thio)ether (DAMTE).
AB  - The present study describes the synthesis of a [99mTc]diaminomercapto(thio)ether
      (DAMTE-derivative) as a first compound of a new class of 99mTc-complexes which is
      tubular excreted. 10-Benzoyl-8-keto-7-aza-2-amino-4,10-dithia-decanoic acid (CO2
      DAMTE 3) was synthesized by the reaction of succinimidyl-S-benzoyl-thioglycolate
      and (S)-2-aminoethyl-L-cysteine. The respective technetium complex, 99mTc-CO2
      DAMTE was obtained in radiochemical yields of about 70% using stannous chloride
      as reducing agent. Hydrolysis of the protecting group was performed either prior
      to the complexation of pertechnetate ("cold kit") or during the labelling
      reaction ("hot kit"). Organ distribution was determined in Wistar rats. Within 24
      h 40% of the activity were excreted into the feces and 43% into the urine,
      whereas 10% were retained in the kidneys. In contrast, a first human study showed
      a very fast renal elimination of 99mTc-CO2-DAMTE, a low liver uptake (< 10%) and
      no retention in the kidneys. The renal clearance of approx. 240 mL/min/1.73 m2 in
      addition to the protein binding of > 95% suggests an effective tubular excretion
      of the compound.

PMID- 9234366
TI  - Highly potent indanamine serotonin uptake blockers as radiotracers for imaging
      serotonin uptake sites.
AB  - Two highly potent indanamine serotonin (5-HT) uptake blockers, trans-3'-(4'
      bromophenyl)-1-indanamine (trans-[11C]DBPI or [11C]Lu 19-056) and its iodo
      analog, trans-3'(4'-[125I]iodophenyl)-1-indanamine (trans-[125I]DIPI) were
      evaluated as radiotracers for imaging 5-HT uptake sites in vivo Trans-[11C]DBPI
      was synthesized by N-methylation of the normethyl precursor with
      [11C]iodomethane. Trans-[125I]DIPI was synthesized by iododestannylation of the
      tributyltin precursor with [125I]NaI. Radiochemical yields for the [11C] and
      [125I] radiotracers were 34 and 40% with specific activities of 4000 and 1800
      mCi/mumol, respectively. In vitro, the iodo analog, trans-DIPI, showed an IC50
      value of 0.26 nM in inhibition of [3H]paroxetine binding to 5-HT uptake sites in
      rat cortex. The potency was found to be equivalent to that of paroxetine or
      McN5652. In vivo, after i.v. injection into mice, both radiotracers showed high
      uptake in brain (3-4% dose/whole brain at 15 min) and high accumulation into
      target tissues such as hypothalamus and olfactory tubercles (7-8% dose/g at 60
      min). The binding was blocked by pre-injection of 5 mg/kg of peroxetine. While
      the in vivo distribution agreed with previously reported 5-HT uptake site
      distribution, the radiotracers showed high uptake in non-target tissues such as
      cerebellum, resulting in low target-to-non-target ratios (1.5-1.6 at 60 min).
      Since washout from non-target regions was slower than from target regions, longer
      time observation with 125I up to 6 h did not improve the ratios. HPLC analyses of
      mouse brain homogenates and blocking studies indicated that the high uptake in
      non-target regions is not the result of metabolism or any interaction of the
      radiotracers with those tissues via specific binding sites. In spite of low
      target-to-non-target ratios, target regions with high density of 5-HT uptake
      sites, such as the raphe nuclei, superior colliculi and substantia nigra, were
      visualized with trans-[125I]DIPI by ex vivo autoradiography, since the
      radiotracer showed high specific binding (total mimus nonspecific binding).

PMID- 9234367
TI  - Evaluation of possible interference of anti-inflammatory drugs upon scintigraphic
      imaging with macrophage targeting 99mTc-J001X: effects of methylprednisolone,
      dexamethasone, indomethacin and methotrexate.
AB  - J001X, an acylated poly-(1,3)-galactoside isolated from Klebsiella pneumoniae
      proteoglycan, has been developed to target cells from the monocyte-macrophage
      lineage. Recent experimental work and initial clinical trials have proved the
      potential of this molecule labeled with 99mTc for the scintigraphy of
      inflammatory foci. In a model of radiation-induced inflammation in pigs, the
      scintigraphic contrast was observed to be very sensitive to a single injection of
      methylprednisolone given 12 h before scintigraphy. The present study was
      undertaken to confirm this effect and to estimate the possible interference of
      various anti-inflammatory agents on the in vivo targeting of macrophages by
      J001X. Methylprednisolone, dexamethasone, indomethacin and methotrexate used at
      an immunosuppressive dose were tested to assess the possible risk of false
      negative examinations in patients thus treated. Analysis of the results indicated
      that among the four drugs tested, only methylprednisolone at 0.5-1 mg/kg could
      interfere with J001X scintigraphy.

PMID- 9234368
TI  - Evaluation of 99mTc-labeled modified serum albumin for tumor detection.
AB  - Serum albumin (SA) modified and labeled with 131I-tyramine N-1'-desoxysorbitol
      (131I-TDS) has been shown to localize in tumors [Sinn et al., (1990) Nucl. Med.
      Biol. Part B 17, 819-827]. We prepared similar TDS complexes labeled with 99mTc
      and evaluated their potential for tumor imaging. Derivatization of SA with TDS
      was optimized using cyanuric chloride or 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide (EDAC) as coupling agents. A high TDS loading yield of 38 mol/mol SA
      was obtained with the latter reagent. Modified SA (8 and 38 mol TDS/mol SA) were
      labeled with 99mTc via the stannous reduction method and injected i.v. into EMT-6
      tumor bearing mice. 125I-TDS-SA (8 mol 125I-TDS/mol SA) revealed a high tumor
      uptake of 10% ID/g at 3 h post-injection. The 99mTc-labeled SA and TDS-SA
      complexes lacked tumor specificity, instead TDS loading of SA resulted in
      increased liver/spleen uptake, suggesting colloid formation. This study confirms
      the potential of modified SA for tumor imaging but highlights the importance of
      choice of radioisotope, as well as site of attachment of the radiolabel to the
      modified SA for optimal tumor localization.

PMID- 9234369
TI  - Cytogenetic damage in marrow cells of mice after injections of yttrium-90-labeled
      monoclonal antibody.
AB  - Chromosome aberrations, micronuclei and sister-chromatid exchanges were
      quantified in marrow cells of athymic nude and B6C3F1 mice at various times up to
      14 days after injection of 90Y-labeled monoclonal antibody CO17-1A. Aberrations,
      predominantly of the chromatid type, were sharply elevated at 24 h post-injection
      then declined in a curvilinear fashion over the 14 days. Micronucleus numbers
      among polychromatic erythrocytes peaked 3-4 days after treatment, then declined
      exponentially but remained at higher than expected levels. Sister-chromatid
      exchanges were roughly double the control rate with no apparent relation to post
      treatment time.

PMID- 9234370
TI  - A new 99mTc-complex with a germanium-hydrazide (GeTH) ligand.
AB  - A new tetrahydrazido-germanium (GeTH) ligand was synthesized, characterized and
      complexed with 99mTc. The negatively charged 99mTc-chelate was shown to form in
      high yields at neutral pH in the absence of other reducing agents and exhibits
      high in vitro and in vivo stability.

PMID- 9234371
TI  - Immunotolerance induced by intratesticular antigen priming: expression of TGF
      beta, Fas and Fas ligand.
AB  - The authors have previously reported that an injection of S-antigen (S-Ag) into
      rat testes prior to immunization induces systemic tolerance (designated orchidic
      tolerance) and protects the animals from experimental autoimmune uveoretinitis
      (EAU) and that the signal for orchidic tolerance induction emigrates from the
      testis within a few hours after antigen priming of the testis. In order to
      understand the mechanism by which the signal or signal carrier is generated, they
      determined in this study changes in immunoreactivity for transforming growth
      factor-beta (TGF-beta), IFN-gamma, IL-2, Fas and Fas ligand in the testis
      following an injection of S-Ag. Immunoreactivity for TGF-beta increased with
      time, reaching a maximum in six hours and declining thereafter. The time required
      for the maximum expression of TGF-beta coincided well with the time-dependent
      profile of orchidic tolerance signal generation within the testis. Little or no
      immunoreactivity was observed for IFN-gamma and IL-2 in normal (control) and S-Ag
      injected testes. Immunoreactivity for Fas and Fas ligand was detected both in
      control and experimental testes and did not change appreciably with time
      following Ag-priming of the testis. Fas immunoreactivity was found in spermatids
      and virtually absent in the interstitial tissue, while Fas ligand
      immunoreactivity was primarily associated with the interstitial cells such as
      Leydig cells. Fas ligand immunoreactivity was very weak, if any, in the germ
      cells and Sertoli cells. These results suggest that TGF-beta and Fas ligand
      expressed in MHC-positive interstitial cells may play an important role in the
      generation of orchidic tolerance induction signal. A preliminary study showed
      that splenocytes preincubated with testis extracts and S-Ag, when transferred to
      naive rats, induced systemic tolerance in recipient animals. Inclusion of anti
      TGF-beta or a carboxyl terminal peptide of Fas in the testis extract reduced the
      potency of incubated splenocytes to induce systemic tolerance in recipient rats.
      These results indicate that generation of the orchidic tolerance signal does not
      require the anatomical structure of the testis but is mediated by molecular
      entities such as TGF-beta and Fas ligand.

PMID- 9234372
TI  - Tumor necrosis factor and nitric oxide production by resident retinal glial cells
      from rats presenting hereditary retinal degeneration.
AB  - The inherited retinal dystrophy observed in Royal College of Surgeons (RCS) rats
      is a widely used model for the study of the photoreceptor degeneration that
      occurs in retinitis pigmentosa and macular degeneration. The visual cell
      degeneration is accompanied by an abnormal accumulation of microglial cells in
      the retina of RCS rats presenting the dystrophy. In the present study, we show
      that combined stimulation of RCS dystrophic retinal Muller glial (RMG) cells with
      interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) induced the release in
      culture supernatants of significantly higher amounts of tumor necrosis factor
      (TNF) and nitric oxide (NO) compared to nondystrophic congenic controls. In
      contrast, the levels of TNF and NO found in the supernatants from microglial
      cells were not significantly different in both strains. Interestingly, as shown
      by thymidine incorporation, microglial cells from RCS dystrophic rats have a
      prominent capacity of proliferation in culture medium compared to microglia
      isolated from RCS non dystrophic controls. Incubation of RMG cells and microglia
      with the stereoselective inhibitor of NOS, NG-monomethyl-L-arginine (L-NMMA),
      inhibited nitrite release in LPS + IFN-gamma-stimulated RMG cells and microglia.
      The addition of TGF-beta with LPS + IFN-gamma clearly inhibited TNF release in
      supernatants from both dystrophic and control rat RMG cells and microglia. While
      TGF-beta significantly inhibited nitrite synthesis in RMG cells, the effect on
      nitrite synthesis by microglia was very low. The retinal dystrophy observed in
      RCS dystrophic rats could result from an abnormal reactivity of RMG and
      microglial cells to release TNF and NO in response to stimulants. The
      immunomodulatory cytokine TGF-beta and inhibitors of NOS could be negative
      regulators in the cytokine network and nitrite synthesis thus interfering with
      the development of photoreceptor cell death.

PMID- 9234373
TI  - Trauma and alkali burns induce distinct patterns of cytokine gene expression in
      the rat cornea.
AB  - Cytokines such as the interleukins (IL) and tumor necrosis factor alpha (TNF
      alpha) have traditionally been associated with paracrine regulation of immune
      reactions. These proteins also have properties suggestive of functional roles in
      the inflammatory and reparative responses to tissue injury. In this study, mRNA
      levels for IL-1 alpha, IL-1 beta, IL-6, TNF alpha, interferon gamma, transforming
      growth factor beta 1, and CD4 were monitored in rat corneas at times from 1 hour
      through 2 weeks after incisional trauma or alkali burns. Transcripts for IL-1
      alpha, TNF alpha, and TGF beta 1 were present in most corneal samples; whereas
      those for IFN gamma and CD4 were not detected. As early as 1 hour following
      either of these non-immunologic forms of injury, expression of IL-6 mRNA levels
      was induced. Only in corneas with alkali burns did IL-6 induction persist from
      days 1 through 7. The alkali-injured corneas also had markedly increased IL-1
      beta mRNA levels from days 1 through 7. These observations indicate that cytokine
      mRNA is induced in the cornea by trauma without an apparent immunologic stimulus.
      Our data are consistent with the hypothesis that corneal tissues respond to
      different types of injury with different patterns of cytokine gene expression.

PMID- 9234374
TI  - Prevention of high risk corneal graft rejection using cyclosporine A (CsA)
      incorporated into a collagen matrix.
AB  - The aim of this work was to compare the efficacy of cyclosporine (CsA) collagen
      shields and fragments in suppressing experimental allograft rejection in an
      animal model for high risk keratoplasty. Altogether 23 experimental animals were
      treated either with plain collagen shields, oral cyclosporine, collagen CsA
      shields, or with CsA collagen fragments after corneal transplantation (PKP) in
      previously vascularized corneas. The study medications were started immediately
      following PKP. For these animals slit lamp examinations were performed twice a
      week for the duration of the experiment and the signs of corneal rejection were
      observed. The animals were followed until an irreversible rejection or until the
      end of the experiment (14-149 days). The inflammation of the graft was also
      evaluated histologically when animals were sacrificed. The grafts treated with
      plain collagen shields all were rejected within 36 days, and the mean graft
      survival time for these corneas was 25 days. Five transplants that were treated
      with oral CsA had better survival, and two of five grafts stayed clear until
      postoperative day 119, when the treatment was stopped. The best graft survival
      was seen in grafts treated with CsA collagen fragments and all these stayed clear
      up to 77 days postoperatively. The treatment of the grafts with CsA collagen
      shields was almost as effective as with CsA fragments, and first signs of
      rejection appeared as late as nine weeks postoperatively in two of seven grafts.
      The other of these rejected corneas were later treated with CsA collagen
      fragments and showed a dramatic improvement in transparency of the cornea and
      disappearance of inflammation of the graft. The discontinuation of study
      medication caused an irreversible rejection to appear in a previously clear graft
      that had been treated successfully with any study medication. We conclude that
      topical CsA in shields or in fragments will provide a significant advance over
      systemic CsA alone, and that CsA fragments appear to be as effective as shields
      in preventing corneal allograft rejection.

PMID- 9234375
TI  - Differential tumor necrosis factor and nitric oxide production in retinal Muller
      glial cells from C3H/HeN and C3H/HeJ mice.
AB  - Tumor necrosis factor (TNF) and nitric oxide (NO) have been shown to play a role
      in the pathogenesis of endotoxin-induced uveitis (EIU) in rats. Susceptibility to
      develop EIU in vivo is correlated with the extent of TNF production by retinal
      Muller glial cells (RMG). Moreover, RMG cells from the susceptible Lewis rat
      strain synthesize high amounts of nitrite under in vitro stimulation. Variations
      in susceptibility to endotoxin are observed among mice strains: C3H/HeN mice are
      known to be susceptible to develop EIU while C3H/HeJ are refractory. We show here
      that treatment of RMG cells from both strains with LPS + IFN-gamma does not
      induce TNF-synthesis in culture supernatants but produces high amounts of NO only
      in the supernatants from activated C3H/HeN RMG cells. The addition of TNF in the
      culture medium containing LPS/IFN-gamma further increases nitrite production in
      C3H/HeN RMG cells and allows the synthesis of low levels of nitrite in C3H/HeJ
      RMG cells. Addition of a specific NO synthase inhibitor, NG-monomethyl-L-arginine
      (L-NMMA), blocks NO release. We have previously shown that intraperitoneal
      injections of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME) which inhibited nitrite and TNF release in the ocular media reduced EIU in
      rat. We conclude here that the in vivo susceptibility to develop EIU in mice is
      correlated with the extent of in vitro nitrite production by RMG cells confirming
      the implication of NO in the induction of ocular inflammation. The low level of
      retinal inflammation observed during EIU in C3H/HeN mice compared to rats could
      be related to the absence of TNF production by RMG cells.

PMID- 9234376
TI  - Secretion of proinflammatory cytokines by human conjunctival epithelial cells.
AB  - The production of cytokines by human conjunctival epithelial cells following
      stimulation was investigated. Primary cultures of human conjunctival epithelial
      cells were characterized by morphology and keratin expression. Cultured
      epithelial cells were treated with varying concentrations of lipopolysaccharide,
      interleukin (IL)-1 beta, calcium ionophore A23187, or phorbol myristate acetate,
      and cytokine secretion was determined over specified intervals. Culture
      supernatants and cell lysates were analyzed by ELISA for IL-1 beta, IL-3, IL-4,
      IL-5, IL-6, IL-8, IL-11, IL-1 receptor antagonist (IL-1ra), tumor necrosis factor
      alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF).
      With the exception of IL-1ra, unstimulated conjunctival epithelial cells produced
      cytokines at relatively low or undetectable levels. IL-1ra was detected in both
      culture supernatants and cell lysates under basal conditions. In response to
      stimuli, conjunctival epithelial cells secreted the proinflammatory cytokines TNF
      alpha, IL-6, IL-8, and GM-CSF in a dose- and time-dependent fashion. After
      stimulation, the intracellular levels of IL-1ra increased in these cells but the
      supernatant-associated levels remained unchanged. None of the other cytokines
      evaluated (IL-1 beta, IL-3, IL-4, IL-5, and IL-11) were detected in supernatants
      or lysates of resting or stimulated cells. These findings suggest that
      conjunctival epithelial cells may contribute to the pathogenesis of human ocular
      diseases by production of proinflammatory cytokines. Further evaluation of these
      cells as targets of therapy is warranted.

PMID- 9234377
TI  - Phenotypic analysis of retinal leukocyte infiltration during combined cyclosporin
      A and nasal antigen administration of retinal antigens: delay and inhibition of
      macrophage and granulocyte infiltration.
AB  - Nasal antigen administration successfully suppresses a model of organ-specific
      autoimmune disease, experimental autoimmune uveoretinitis (EAU), when
      administered prior to immunisation. We have previously shown that nasal antigen
      therapy for active disease or in primed, sensitised animals does not reliably or
      consistently suppress histological disease. However, when nasal antigen
      administration is combined with cyclosporin A (CsA) therapy, rod outer segment
      destruction (target organ) is reduced despite the presence of clinical and
      histological leukocytic infiltration of the eye. In this study, two colour flow
      cytometric phenotypic analysis of retinal and choroidal leukocytic infiltration
      of animals treated with either CsA alone, combined therapy with CsA and
      inhalational tolerance therapy with retinal antigens or sham treated controls was
      performed. There was no clinical difference between the two treated groups. Flow
      cytometric phenotypic analysis was performed in all groups at both maximal
      clinical disease and during resolution of clinical signs. Although the cell
      number within the infiltrate was reduced in combined treated group, CD4+ IL-2R+ T
      cells were still present in large numbers, in contrast to the markedly reduced
      numbers of ED7+ (macrophages/granulocytes) cells infiltrating during height of
      disease. In the CsA-nasal antigen treated group, when clinical inflammation had
      subsided, an increase in both macrophages and granulocyte numbers in the
      chorioretina was observed. The cell numbers were always less than CsA-only
      treated animals. Despite the late cellular influx of monocytes/macrophages, rod
      outer segment (ROS) integrity as determined histologically, was maintained. Nasal
      antigen administration of retinal antigens in CsA-only treated animals (combined
      therapy group) protects against target organ damage without inhibiting activated
      T cell traffic to the eye. These results suggest that recruitment of macrophages
      to the target tissue is central to autoimmune target organ damage, the mechanisms
      of which are discussed.

PMID- 9234378
TI  - Immunology and ocular manifestations of giant cell arteritis.

PMID- 9234379
TI  - Cyclin D1 overexpression in malignant lymphomas.
AB  - Cyclin D1, the regulatory subunit of certain protein kinases thought to advance
      the G1 phase of the cell cycle, is now established as a proto-oncogene, with
      evidence indicating that its derangement may contribute to the uncontrolled cell
      growth characteristic of tumors. The chromosomal translocation t(11;14)(q13:q32),
      involving rearrangement of the BCL-1 locus, is closely associated with human
      lymphoid neoplasia affecting mantle cell lymphomas (MCL). Recently, the putative
      BCL-1 proto-oncogene turned out to be none other than the cyclin D1 gene.
      Although the observed break points in the BCL-1 locus are not tightly clustered,
      its rearrangement has been documented in 40-70% of cases of mantle cell lymphoma,
      whereas it only rarely occurs in other B cell lymphomas. Of note, all of the
      known break points leave the cyclin D1 coding region structurally intact and
      result in increased protein expression, implying that this may provide a highly
      sensitive and specific marker for MCL. Recent studies demonstrated that
      immunohistochemical detection in paraffin-embedded material, using a monoclonal
      antibody, is very useful for routine diagnosis. Current knowledge of cyclin D1
      overexpression in malignant lymphomas, with emphasis on its clinicopathologic
      significance, is reviewed.

PMID- 9234380
TI  - Suppressive effects of sairei-to on monoclonal antibody 1-22-3-induced
      glomerulonephritis: analysis of effective components.
AB  - The effects of traditional Chinese medicine (Sairei-to) on experimental
      glomerulonephritis induced in rats by monoclonal antibody (mAb) 1-22-3 injection
      was examined. The level of proteinuria in the Sairei-to-treated group was
      significantly lower than that in the PBS treated group. This suppressive effect
      was caused by the major component of Sairei-to, Syo-saiko-to but not by another
      component, Gorel-san. The suppressive effect of Syo-saiko-to was identified in
      its components (Bupleuri radix, Pinelliae tuber and Zingiberis rhizoma), but not
      in the other combined components (Ginseng radix and Zizyphi fructus). Further
      study revealed that the suppressive effects of the combined components were
      mainly derived from Bupleuri radix. It was demonstrated that the actual active
      ingredient is probably Saikosaponin-d. Light microscopy revealed that Sairei-to
      and its effective components suppressed the proliferation of mesangial cells and
      mesangial matrix expansion. Semiquantitative morphological studies of glomerular
      lesions on the eighth day showed that Syo-saiko-to and its combined components
      (Bupleuri radix, Zingiberis rhizoma and Pinelliae tuber) suppressed mesangial
      matrix expansion significantly compared with phosphate-buffered saline control
      groups (matrix score: 28.0 +/- 19.1 vs 102.3 +/- 14.1; 30.9 +/- 30.1 vs 102.3 +/-
      14.1, P < 0.005, respectively). It was concluded that Saikosaponin-d, as well as
      Bupleuri radix, Syo-saiko-to and Sairei-to can suppress proteinuria and
      morphological changes in the rat glomerulonephritis model induced by mAb 1-22-3.

PMID- 9234381
TI  - Genetic mapping of genes regulating the thymus size in back-cross rats between
      the laboratory BUF/Mna strain and the MITE strain derived from the wild rat,
      Rattus norvegicus.
AB  - The thymoma prone BUF/Mna (B) rat is a useful model for studying the genes
      responsible for thymus enlargement during the stage of young growth. Among the
      strains of rats, B rats have the largest thymuses at all stages of life. A locus,
      Ten-1, which contributes to thymus enlargement in back-cross (BC) rats between
      the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the
      precise location of the locus, ?B x(B x MITE)F1? BC rats were generated by
      crossing the B strain with the inbred MITE (M) strain, which was established from
      captured, Japanese wild rats, and were examined by linkage study using polymerase
      chain reaction with 67 microsatellite markers. Linkages with thymus enlargement
      were found in genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11,
      and D1MIt6, by chi2-test and Student's t-test, which confirmed the presence of
      the genetic locus associated with thymus enlargement, Ten-1, in this region.
      Paradoxically, a suppressive locus, Tsu-1, to thymus enlargement was also found
      on chromosome 3, showing linkages of phenotype of the small thymus with genotypes
      of SCN2A, CAT, D3MIt16, and D3MIt13. By analyses of MAPMAKER/EXP and
      MAPMAKER/QTL, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1
      and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.

PMID- 9234382
TI  - Malignant lymphoma induction of rabbits with oral spray of Epstein-Barr virus
      related herpesvirus from Si-IIA cells (HTLV-II-transformed Cynomolgus cell line):
      a possible animal model for Epstein-Barr virus infection and subsequent virus
      related tumors in humans.
AB  - Malignant lymphoma (ML) was induced in eight of nine rabbits inoculated by oral
      spray of the cell-free pellets from Si-IIA culture (HTLV-II-transformed leukocyte
      cell line of the Cynomolgus-producing Epstein-Barr virus (EBV)-related
      herpesvirus) after 64-141 days. None of the rabbits inoculated with EBV from B-95
      8 cells or HTLV-II from MOT cells developed ML. Malignant lymphomas were usually
      of diffuse, large-cell or mixed type. HTLV-II infection was excluded by the
      polymerase chain reaction (PCR) and the particle agglutination test. EBV-encoded
      RNA-1 and EBV-related DNA were detected in the tumor tissues by in situ
      hybridization and PCR, respectively. Anti-viral capsid antigen of EBV antibody
      (anti-VCA) was observed 3 weeks after oral inoculation of Si-IIA cell-free
      pellets. Polymerase chain reaction revealed continuous detection of EBV-related
      virus DNA in the peripheral blood leukocytes from 3 days after oral inoculation.
      These results show that ML induced orally with Si-IIA cell-free pellets was
      caused by EBV-related herpesvirus harbored by Si-IIA cells. Oral spray of EBV
      from B-95-8 also induced EBV infection in rabbits, which was confirmed both by
      the presence of anti-VCA and by PCR. These oral infection and malignant lymphoma
      induction systems of rabbit using EBV-related virus from Si-IIA or human EBV are
      useful animal models for the study of EBV infection and EBV-related lymphomas in
      humans.

PMID- 9234383
TI  - Latent infection with Epstein-Barr virus in odontogenic disorders: comparison
      among ameloblastoma, dentigerous cyst and odontogenic keratocyst.
AB  - In order to investigate the relationship between Epstein-Barr virus (EBV) latent
      infection and histogenesis of odontogenic disorders, in situ hybridization for
      EBV-encoded small RNA (EBER) was applied to the paraffin sections of
      ameloblastoma, dentigerous cyst, and odontogenic keratocyst. Eight cases (15%) of
      53 ameloblastomas showed scattered signals for EBER in the parenchymal cells,
      whereas no reaction of EBER transcript was observed in the non-neoplastic cystic
      lesions. In the ameloblastoma, the follicular and plexiform types revealed the
      signals in the nuclei, but cystic, acanthomatous, granular, and basal cell types
      exhibited no reaction with EBER. The distribution of the signals without
      monoclonarity indicated that ameloblastoma cells may exclude EBV genomes or
      inactivate EBER-encoded genes. The results suggested that EBV participates as one
      of the transforming factors in the occurrence of ameloblastoma.

PMID- 9234384
TI  - Mucin-producing adenocarcinoma of the lung, with special reference to goblet cell
      type adenocarcinoma: immunohistochemical observation and Ki-ras gene mutation.
AB  - To clarify its biological nature, 10 samples of goblet cell-type adenocarcinoma
      of the lung were collected and compared with 10 other pulmonary mucin-producing
      adenocarcinomas with respect to immunohistochemical features and the presence of
      Ki-ras gene mutation in codons 12 and 13. Goblet cell-type adenocarcinomas lacked
      immunoreactivity for surfactant apoprotein and S-100 protein-positive Langerhans
      cells, which was in marked contrast to other mucin-producing adenocarcinomas. In
      addition, the mucin gene products, MUC-1 and MUC-2 glycoproteins were
      immunohistochemically stained. The results showed that MUC-1 glycoprotein is
      frequently expressed by mucin-producing adenocarcinomas except the goblet cell
      type. Ki-ras gene mutation was detected in 12 of 20 (60%) mucin-producing
      adenocarcinomas. These mutations were exclusively found in codon 12 and G to A
      transitions were the most frequent type of alteration in the Ki-ras gene. In
      goblet cell-type adenocarcinomas, the frequency of Ki-ras gene mutation was 80%
      consisting of G to A transitions and G to T transversions in six and two tumors,
      respectively. Therefore, goblet cell-type adenocarcinomas differed from other
      mucin-producing adenocarcinomas in terms of immunohistochemical and molecular
      biological features, suggesting that goblet cell-type adenocarcinomas are
      distinctly different from other subtypes of adenocarcinomas.

PMID- 9234385
TI  - Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the
      lung.
AB  - The expression of matrix metalloproteinase-2 (MMP-2; 72 kDa type IV
      collagenase/gelatinase A) and MMP-9 (92 kDa type IV collagenase/gelatinase B) was
      immunohistochemically investigated in 79 T1 adenocarcinomas of the lung using non
      commercial polyclonal anti-MMP-2 and -9 antibodies. Thirty-two (41%) and 22 (28%)
      among the 79 cases were positive in the tumor cells for MMP-2 and -9,
      respectively. The incidences of MMP-2 and -9 immunoreactivities were higher (64
      and 45%, respectively) in poorly differentiated tumors than in well
      differentiated tumors (36 and 25%, respectively), and lower in bronchioloalveolar
      carcinoma (22 and 10%, respectively) compared with other subtypes of
      adenocarcinoma. The prognosis for patients with MMP-2 and/or -9 positive
      immunoreactivities was significantly poorer than for those with a MMP-negative
      tumor (P < 0.05). The degree of collagenization was divided into four grades, and
      tumors with a small to abundant amount of collagen (grade 2 and grade 3 fibrosis)
      had a higher incidence of immunoreactivity to both types of MMP. It is estimated
      that these expressions might be responsible for tumor invasion, metastasis, and
      for grade 2 and grade 3 fibrosis in T1 adenocarcinoma of the lung.

PMID- 9234386
TI  - Expression of p21WAF1/CIP1 in colorectal adenomas and adenocarcinomas and its
      correlation with p53 protein expression.
AB  - The expression of p53-inducible cyclin-dependent kinase inhibitor, p21WAF1/CIP1
      in non-neoplastic mucosa, adenoma and adenocarcinoma of the colorectum was
      examined by immunohistochemistry and western blotting and its relation with the
      expression of p53 protein was analyzed. Non-neoplastic epithelial cells at the
      surface area showing no proliferative activity expressed p21WAF1/CIP1. The
      expression of p21WAF1/CIP1 was immunohistochemically detected in 55% (206/377) of
      the adenomas and 66% (190/289) of the adenocarcinomas, respectively. The
      incidence of strongly positive cases was significantly higher in the
      adenocarcinomas (27%) than in the adenomas (18%) (P < 0.05). The incidence of
      cases with strong p21WAF1/CIP1 expression was higher in stages 0, 1 and 2
      carcinomas than in stages 3 and 4 carcinomas (P < 0.05). A decrease in the
      incidence of cases with strong expression was detected in carcinomas invading
      deeper than muscularis propria. The incidence of strongly positive cases was
      significantly lower in carcinomas with lymph node metastasis than those without
      metastasis (P < 0.05). The expression of p21 as well as p53 detected by western
      blotting was compatible with the results of immunohistochemistry in most cases
      examined. However, there was no significant correlation between the expression of
      p21WAF1/CIP1 and the abnormal accumulation of p53. These findings overall suggest
      that: (i) the physiological expression of p21WAF1/CIP1 may be associated with
      cellular senescence of colorectal mucosa; (ii) reduced expression of p21WAF1/CIP1
      may participate in the progression of colorectal carcinoma; and (iii) p53
      independent pathway may be considerably involved in the induction of
      p21WAF1/CIP1.

PMID- 9234387
TI  - Restoration of Leydig cells after repeated administration of ethane
      dimethanesulfonate in adult rats.
AB  - Adult male rats were repeatedly treated with ethane dimethanesulfonate (EDS), an
      agent known to destroy Leydig cells selectively. Following a second injection,
      changes in serum testosterone levels and histological and morphometric changes of
      Leydig cells showed the time course to be similar to those after the first
      treatment. The number and volume of Leydig cells markedly decreased at day 2,
      began to increase from day 7, and recovered to the values of the control rats at
      day 30, concomitant with the changes of serum testosterone levels. Cells in the
      interstitial tissue labeled with bromodeoxyuridine markedly increased in number
      at day 2, gradually decreased thereafter, and returned to the values of the
      controls at day 14. During this period, cells undergoing mitosis were seen, their
      type unable to be determined, but were presumed to be regenerating Leydig cells.
      Even 30 days following four treatments with intervals of 30 days each, serum
      testosterone levels were the same as those in the controls. Also the numerical
      and volume densities of Leydig cells and the volume of an average Leydig cell
      were the same as those of the controls. Mitosis was observed in mature Leydig
      cells at this period, if any. It appears that new Leydig cells began to
      proliferate by division earlier than 14 days after EDS, allowing that there were
      several stages of proliferation, and that the source of reappearing Leydig cells
      may not be a limited number of precursor cells, implying the presence of stem
      cells for Leydig cells.

PMID- 9234388
TI  - Columnar cell carcinoma of the thyroid.
AB  - A case of columnar cell carcinoma of the thyroid occurring in a 50-year-old
      female is described. Histologically, the 2 cm tumor showed a prominent papillary
      architecture with thin fibrous cores covered by columnar cells and marked nuclear
      stratification. It also showed microfollicular, glandular, and solid patterns.
      The nuclear features were different to those of conventional papillary carcinoma
      and similar to those of follicular tumors. The tumor was principally encapsulated
      with vascular and minimal capsular invasion. The tumor cells were positive for
      thyroglobulin. The tumor was DNA diploid with a low S phase traction as
      determined by flow cytometry. The patient had no lymph node or distant
      metastasis. The patient was well and without disease 9 months after surgery. The
      possibility that the neoplasm is one of poorly differentiated thyroid carcinomas
      rises.

PMID- 9234389
TI  - Adrenal rest tumor of the broad ligament: case report with immunohistochemical
      study of steroidogenic enzymes.
AB  - An adrenal rest tumor of the broad ligament was studied in a 43-year-old woman.
      The tumor measuring 6 x 3 x 3 cm and appearing as golden-yellow on the cut
      surface was incidentally discovered during a total hysterectomy due to uterine
      leiomyoma. The encapsulated tumor was predominantly composed of pale and lipid
      rich cells arranged in alveolar clusters or short blunt cords. Electron
      microscopic examination revealed mitochondria with tubulo-vesicular cristae and
      abundant lipid droplets. Adrenal 4-binding protein, a transcriptional factor of
      steroidogenesis, was present in almost all of the tumor cells, suggestive of
      steroidogenic features in the lesion. Immunoreactivity of steroidogenic enzymes
      involved in adrenocortical steroid production was detected in the tumor cells,
      suggesting that tumor cells had the potential to synthesize adrenocortical
      steroids. A relatively low Ki-67 labelling index (3.20 +/- 1.15 per 100 tumor
      cells) and an absence of necrosis and vascular and/or capsular invasion suggest
      benignity of the lesion.

PMID- 9234390
TI  - Small cell carcinoma arising from the outer urethral orifice: a case report
      examined by histologic, ultrastructural and immunohistochemical methods.
AB  - A case of small cell carcinoma arising in the outer urethral orifice is
      presented. The resected tumor showed a proliferation of small round or fusiform
      neoplastic cells in the submucosa. Tumor cells were arranged in sheets or a
      trabecular manner and possessed markedly hyperchromatic nuclei with a high N:C
      ratio, closely resembling small cell carcinoma of the lung. Characteristically,
      pagetoid intraepithelial spreading could be identified. However, there was no
      evidence of in situ transitional cell carcinoma and adeno- or squamous cell
      carcinoma components anywhere. Ultrastructurally, each tumor cell contained only
      a few membrane-bound cored granules measuring 60-100 nm, which were compatible
      with neurosecretory granules, and desmosome-like intercellular attachments, but
      lacked aggregated microfilaments. By immunohistochemical examination, tumor cells
      were positive for epithelial markers, such as cytokeratin and epithelial membrane
      antigen, and neuron specific enolase, but negative for any other neuro-endocrine
      markers. Extensive systemic examination failed to show the primary site to be
      other than the outer urethral orifice. These findings indicate that the current
      tumor is a small cell carcinoma with neuro-endocrine differentiation arising from
      the outer urethral orifice.

PMID- 9234391
TI  - Mucinous adenocarcinoma arising in a giant urachal cyst associated with
      pseudomyxoma peritonei and stromal osseous metaplasia.
AB  - An unusual urachal lesion, which is a mucinous adenocarcinoma arising in a giant
      urachal cyst and is associated with pseudomyxoma peritonei and stromal osseous
      metaplasia of the cyst wall, was examined in a 45-year-old male. The cyst was
      encapsulated, measured 22 x 20 x 20 cm and weighed 3800 g. The unilocular cavity
      was filled with mucin. Most of the cystic cavity was lined with tall, simple or
      stratified columnar epithelium with a focus of papillary projection into the
      cavity. These findings suggest that this cystic lesion represents cystadenoma
      rather than a simple cyst. Foci of invasive moderately differentiated mucinous
      adenocarcinoma were detected in the area of macroscopic papillary fronds.
      Carcinoembryonic antigen and CA19-9 were immunohistochemically positive for tumor
      cells and their serum levels were also elevated. Stromal dystrophic calcification
      was extensively observed in the cyst wall with foci of osseous metaplasia.
      Mucinous implants, which histologically demonstrated adherent mucinous masses
      without epithelial components on the surface, were observed in the pelvic and
      abdominal cavity, indicating pseudomyxoma peritonei.

PMID- 9234392
TI  - Successful health and safety management.

PMID- 9234393
TI  - Lessons from perfusion surveys.

PMID- 9234394
TI  - Safety: a manufacturer's perspective.

PMID- 9234395
TI  - Perfusion education in the USA.

PMID- 9234396
TI  - Perfusion education and certification in Europe.

PMID- 9234397
TI  - The School of Clinical Perfusion Sciences.

PMID- 9234398
TI  - Perfusion standards and guidelines.

PMID- 9234399
TI  - Outcomes analysis in cardiac surgery.
AB  - Outcomes research is a quantitative assessment of the results of care. Outcomes
      analysis provides information that benefits the physician, the patient, the
      institution and the health care purchasers. It provides relevant and timely
      information for the assessment of the heart centre's performance. Outcomes data
      have proven to be useful to the attending physicians by providing a basis for
      clinical decision making. Patients may be appraised of the usual results and the
      risks of various treatment strategies and make informed decisions on their care.
      The purchasers of health care will be better informed regarding the costs and
      effectiveness of the care being delivered. O'Connor et al. have stated that
      methods of improving care are often discussed but are difficult to achieve due to
      processes of care being hidden from view. Outcomes research is a comprehensive
      performance evaluation strategy that may be used to discover the impact of these
      hidden aspects of care. This technology of the patient's experience is bringing
      cardiac surgery to a new level of excellence.

PMID- 9234400
TI  - Helicopter engine protection.

PMID- 9234401
TI  - Health technology assessment--principles, pointers and problems.

PMID- 9234403
TI  - Age, breed, sex and seasonality as risk factors for equine laminitis.
AB  - A case-control study was conducted at the Texas Veterinary Medical Center between
      January 1, 1986 and December 31, 1991. Logistic regression was used to assess
      age, breed, sex, and seasonality as risk factors for equine laminitis. There were
      70 acute cases, 183 chronic cases, and 779 controls. No statistical association
      was found between age, breed, sex, or seasonality and the diagnosis of acute
      laminitis. For chronic cases, the estimated odds ratio was statistically
      significant for age (OR = 1.05, 95% CI (1.02, 1.08)) and for the diagnosis of
      laminitis in the third quarter of the year (OR = 2.57, 95% CI (1.55, 4.25))
      relative to the first quarter. There was no statistical association between breed
      or sex and chronic laminitis.

PMID- 9234402
TI  - Assessing infections at multiple levels of aggregation.
AB  - The patterns of sero-prevalence of antibodies to four infectious diseases,
      representing a broad range of pathogens (bacteria: brucellosis; mycoplasma:
      contagious bovine pleuropneumonia; viruses: infectious bovine rhinotracheitis;
      protozoa: trypanosomosis) were investigated at three levels of organization
      (farm, area and district). Three contrasting districts in Kenya were compared: an
      arid and pastoral area (Samburu); a tropical highland area (Kiambu), and a
      tropical coastal area (Kilifi). Cattle in three districts were selected by two
      stage cluster sampling between August 1991 and 1992. Schall's algorithm, a
      generalized linear mixed model suitable for multi-level analysis, was compared to
      ordinary logistic regression (OLR), which ignores clustering of responses;
      generalized estimating equations (GEE) or Jacknife, to account for clustering at
      the farm level; SAS VARCOMP, which provides normal-theory random-effects models.
      Schall's algorithm provided similar estimates to GEE (regression effects) and
      Jackknife (standard errors) for farm-level clustered data. Extending Schall's
      procedure for additional district and area-within-district random effects usually
      provided additional information. In general, models that included only a farm
      level random effect consistently provided larger estimates of farms' variance
      components than did models with additional district and area random effects. The
      four type diseases exhibited various amounts of clustering. Brucellosis had
      moderate farm clustering plus some area and district clustering. Contagious
      bovine pleuropneumonia had only a small amount of clustering, mostly by area.
      Infectious bovine rhinotracheitis exhibited a large amount of clustering,
      primarily at the farm level. Trypanosomiasis antibody prevalence varied by
      district, area and farm. We believe that patterns of disease clustering
      identified by multi-level analysis can be used to better target high-risk units
      for disease control and guide research to understand disease transmission
      factors.

PMID- 9234404
TI  - Health status of preweaned dairy heifers in the United States.
AB  - The first national estimates of mortality and morbidity for preweaned dairy
      heifers in the US were generated from monitoring heifers from 906 operations in
      28 states prospectively using a daily diary card system. Results indicated that
      the cumulative mortality incidence risk from birth to 8 weeks of life was 6.3%
      with a peak of 1.9% during the first week of life. Season of birth was
      significantly associated with cumulative mortality incidence risk, and mortality
      risk was highest in the periods January to March and October to December.
      Cumulative incidence risk of diarrhea to 8 weeks of age was 24.6% with a peak of
      15.4% during the second week of life. Diarrhea incidence risk varied by region,
      with the West having the highest incidence risk (30.5%) and the Northeast the
      lowest (19.2%), as well as by herd size, with the smallest herd size having the
      lowest reported incidence risk of diarrhea to 8 weeks of age (18.8%). Other
      reported 8 week cumulative disease incidence risks included listlessness, 10.0%;
      respiratory disease, 8.4%; dehydration, 4.1%; lameness or joint problems, 1.1%.

PMID- 9234405
TI  - Patterns of health maintenance on Michigan equine operations.
AB  - Data from two 12 month prospective monitoring programs that followed management,
      economics and animal health from randomly-sampled equine operations in Michigan
      were used to determine patterns of health maintenance. Health maintenance
      measures were grouped, and average uses per year were computed for the most
      common measures reported: respiratory, Potomac Horse Fever, neurological and
      multiple-system vaccinations, deworming, and general farrier work. Factors
      examined for potential association with health maintenance measure use were
      numbers of equids and horse-days on the operation, average age of equids, disease
      prevention management procedures, and operation and individual equine activities.
      The most-common vaccinations reported were respiratory vaccines (administered an
      average of 0.9 times per equid per year, of which 61% were for rhinopneumonitis).
      Multiple-system, Potomac Horse Fever and neurological vaccines were given on
      average 0.9, 0.9 and 0.7 times per equid per year, respectively. Deworming
      treatments were administered approximately 2.7 times per equid per year, of which
      64% were ivermectin. Overall farrier work was reported 3.3 times per equid per
      year, trimming was done 2.9 times and shoeing was done 1.5 times per equid per
      year. In general, operations with active equids engaged in training, breeding or
      showing showed increased use of health maintenance measures. Overall use of
      health maintenance measures in the Michigan equine operations monitored did not
      appear to reach recommended levels, because many operations reported no use of
      these measures. However, on operations where health maintenance measures were
      reported, operators were using these measures at or near recommended levels.

PMID- 9234406
TI  - An overview of techniques for dealing with large numbers of independent variables
      in epidemiologic studies.
AB  - Many studies of health and production problems in livestock involve the
      simultaneous evaluation of large numbers of risk factors. These analyses may be
      complicated by a number of problems including: multicollinearity (which arises
      because many of the risk factors may be related (correlated) to each other),
      confounding, interaction, problems related to sample size (and hence the power of
      the study), and the fact that many associations are evaluated from a single
      dataset. This paper focuses primarily on the problem of multicollinearity and
      discusses a number of techniques for dealing with this problem. However, some of
      the techniques discussed may also help to deal with the other problems identified
      above. The first general approach to dealing with multicollinearity involves
      reducing the number of independent variables prior to investigating associations
      with the disease. Techniques to accomplish this include: (1) excluding variables
      after screening for associations among independent variables; (2) creating
      indices or scores which combine data from multiple factors into a single
      variable; (3) creating a smaller set of independent variables through the use of
      multivariable techniques such as principal components analysis or factor
      analysis. The second general approach is to use appropriate steps and statistical
      techniques to investigate associations between the independent variables and the
      dependent variable. A preliminary screening of these associations may be
      performed using simple statistical tests. Subsequently, multivariable techniques
      such as linear or logistic regression or correspondence analysis can be used to
      identify important associations. The strengths and limitations of these
      techniques are discussed and the techniques are demonstrated using a dataset from
      a recent study of risk factors for pneumonia in swine. Emphasis is placed on
      comparing correspondence analysis with other techniques as it has been used less
      in the epidemiology literature.

PMID- 9234407
TI  - Economics of health management in the Michigan, USA equine industry.
AB  - A study was developed to describe direct expenses, labor use, and performance
      days lost associated with health management in the Michigan equine industry. A
      prospective design with stratified, random sampling, was employed involving 77
      operations from February 1992 through January 1993, and 61 different operations
      from May 1993 through April 1994. Data on the cost of health management were
      collected during monthly visits, and included monetary expenditures, death
      losses, days lost, and labor use. Median health care costs (when they were
      incurred) were $4.84 per horse per month for monetary expenditures plus death
      losses, 0.20 hours per horse per month for labor use, and 0.81 performance days
      lost per horse per month for therapy and prevention of all diseases combined.
      There were large variations both within and between specific disease groups,
      operation-size strata, and months. General linear models indicated that health
      management costs (when incurred) were significantly higher (per horse per month)
      on smaller operations. The only disease group that showed a significant
      difference between months was respiratory disease. However, these differences did
      not appear to demonstrate a definitive seasonal pattern. Monetary expenditures
      and labor use for management of lameness tended to be lower on operations with
      more riding and showing activities. Also, monetary expenditures to manage
      lameness tended to be lower on operations with a higher proportion of
      conditioning activity. Our results are consistent with other studies, and
      implications for management and future research are discussed.

PMID- 9234408
TI  - Calf health in cow-calf herds in Switzerland.
AB  - In 1993, an observational study was initiated to provide general information on
      animal health in extensive beef farms, to estimate disease frequency and the
      economic impact of calf diseases and to identify risk factors related to health
      and weight gain. The longitudinal study was conducted from fall 1993 until winter
      94/95 and included 100 farms in western Switzerland. The basic concept was to
      follow one generation of calves on these farms and record all events concerning
      animal health from birth to weaning. The study population included 1270 calves
      (most were Angus crossbreds). Farm-management data were collected with a
      questionnaire conducted on the farm. Birth and weaning weights were obtained from
      the beef cattle breeding association. Clinical diagnoses and treatment costs were
      provided by the farm veterinarians. Two thirds of the dead calves were submitted
      to a complete postmortem examination. Fifty-three percent of the farms in the
      study were primary type income farms while 47% were secondary type income farms.
      Thirty-eight percent of the farms were situated in the lower areas of
      Switzerland, 14% in the prealpine foothills, the remaining 48% were located in
      mountain areas. Preweaning calf mortality was 5%. The main causes of calf deaths
      were respiratory diseases and digestive disorders. Twenty-two percent of the
      calves were treated at least once by a veterinarian; 36% of the treatments
      administered by the veterinarian were applied because of diarrhea, 27% because of
      respiratory diseases. Disease incidence was highest during the months of
      November, December and January. The association of disease and potential farm
      level risk factors was analysed using chi 2-statistics and multivariable
      regression methods including generalized estimating equations to adjusted for
      herd effects. Specific risk factors for disease were not identified. Treatment
      for disease was not associated with 250-day standardized weight gain.

PMID- 9234409
TI  - Risk factors for colic in the Michigan (USA) equine population.
AB  - A population-based prospective epidemiological study was conducted to assess risk
      factors for equine colic. A stratified sample of 3925 equids in 138 randomly
      selected equine farms in the state of Michigan was monitored in two 12-month
      rounds of data collection. Incidence densities were used to describe the rate of
      development of colic in the study population. Mortality rates, case fatality
      rates and survival rates were used to describe the severity of colic on the study
      population. Multivariable logistic regressions with random effects (grouped
      according to farm) were used to identify risk factors associated with occurrence
      of colic. A total of 3175 equids from 132 farms from the starting population of
      3925 equids in 138 farms was used in the multivariable analysis. There were 77
      cases of colic reported during the study period in 62 animals. Of these animals,
      54 (87%) had one case, 5 (8%) had two cases, 2 (3%) had three cases, and 1 (2%)
      had seven cases. Of the cases reported, 49 (64%) were non-specific diagnoses, 13
      (17%) impaction/acute intestinal obstruction colics, 7 (9%) spasmodic colics, 4
      (5%) sand colics, 2 (3%) gas colics, 1 (1%) verminous mesenteric arteritis, and 1
      (1%) enteritis due to ingestion of moldy grain. The annual incidence density of
      colic in the study was 3.5 cases per 100 equid-years. The surgical treatment risk
      was 17% (13/77). The overall mortality risk due to colic was 0.5 deaths per 100
      equids, and the case fatality risk was 13% (10/77). The case fatality risk for
      cases treated surgically was 31% (4/13), while the case fatality risk for non
      surgical colics was 10% (7/69). Risk factors associated with significantly
      increased likelihood of developing colic were foaling during the study, deworming
      during the study, increased age, and participation in showing activities.
      Geldings and equids provided group drinking water from sources other than tanks,
      buckets and automatic waterers were significantly associated with reduced risk of
      colic.

PMID- 9234410
TI  - A modelling approach to the quantification of the benefits of a national
      surveillance programme.
AB  - A simulation modelling approach was developed to investigate the effects of a
      reduction in funding for animal health surveillance on the probability of
      diagnosis of a currently-exotic species of Salmonella if it were introduced into
      New Zealand. Both severe and mild clinical-disease outbreaks were hypothesized.
      The probabilities of diagnosis for a single outbreak on a cattle farm under the
      current surveillance programme were 0.742 and 0.328 for severe and mild clinical
      disease episodes respectively, reducing to 0.018 and 0.005 respectively under the
      reduced surveillance programme. The impacts of these probabilities on the likely
      time delays from introduction into New Zealand before a definitive diagnosis was
      reached and the resultant numbers of infected properties were estimated for three
      different epidemic scenarios. For the best-case epidemic, the median time to
      diagnosis under the current surveillance programme was 4 weeks (by which time
      there was still only the index property infected), but under the reduced
      surveillance programme, the median time to diagnosis was over 1.5 years. Under
      the most-likely epidemic scenario, the mean time to diagnosis under the current
      programme was 4 weeks (by which stage there were two infected properties),
      whereas the median time to diagnosis under the reduced programme was 40 weeks (by
      which time there were 88 infected herds). With the worst-case epidemic, the
      median time to diagnosis under the current surveillance programme was still 4
      weeks with only two infected properties; however the median time to diagnosis
      under the reduced programme was 33 weeks by which stage there were 90 infected
      farms.

PMID- 9234411
TI  - A risk-assessment model for foot and mouth disease (FMD) virus introduction
      through deboned beef importation.
AB  - We present a risk-assessment model to assess the risk of introduction of foot and
      mouth disease (FMD) virus associated with deboned beef importation. The model was
      developed in accordance with the risk-reduction procedures proposed by the
      European Community for meat importation. The risk reduction procedures include
      farm-level inspection, ante-mortem inspection, post-mortem inspection, chilling
      and deboning. The risk assessment was based on the prevalence of FMD-infected
      cattle in herds as well as the prevalence of infected herds in the exporting
      country. Computer simulations were carried out to evaluate the probability of FMD
      virus introduction by importing 100 tons of deboned beef in relation to FMD
      prevalence, number of cattle selected from each herd, and sample sizes in ante
      mortem and post-mortem inspections. The effects of the risk-reduction procedures
      on the probability of FMD virus introduction were examined.

PMID- 9234412
TI  - Impact of biological factors on the interpretation of bovine trypanosomosis
      serology.
AB  - A total of 457 cattle from dairy farms in Mukono County, Uganda, were
      investigated for Trypanosoma antibodies by ELISA. The objective of the study was
      to identify explanatory covariate factors for seropositivity among nine farm
      specific and four animal-specific variables. We used logistic regression models
      for parasitological and serological outcome variables and then compared the
      adjusted odds ratios for explanatory factors between the models. Age is
      positively correlated with seropositivity but not with the detection of the
      parasite. Therefore, age group-specific cut-off values were established using
      mixture-distribution analysis. This procedure, as well as a mixture-distribution
      derived cut-off value for the total sample, resulted in a greater relative
      efficiency of the ELISA as compared to conventional interpretation (cut-off value
      defined using non-exposed negative controls). The relevance of age and other
      biological factors for the serological status is briefly discussed.

PMID- 9234413
TI  - Risk factors for seroprevalence of ovine lentivirus in breeding ewe flocks in
      Nebraska, USA.
AB  - The prevalence of and risk factors for ovine lentivirus (OLV) infection in 1466
      breeding ewes in nine US Meat Animal Research Center (MARC) flocks were
      determined using a recombinant transmembrane protein (PTM) enzyme-linked
      immunosorbent assay (ELISA) to detect serum anti-OLV antibodies and define
      infection. Based on multivariable logistic regression, confinement birth and
      rearing (odds ratio (OR) = 1.6), older weaning ages (OR = 1.1 week-1), and older
      age (OR = 1.3-2.5 year-1 beyond age 1 year) were significantly associated with
      higher OLV prevalence in ewes. Prevalence also varied significantly by flock,
      with Finnsheep and Texel ewes having the highest prevalences and Booroola Merino
      and Suffolk ewes having the lowest prevalences. These findings support the
      hypothesis that management control efforts should concentrate on events early in
      the life of sheep, as this period is associated with factors which can modulate
      the risk for OLV infection.

PMID- 9234414
TI  - The prevalence of serum antibodies to tick-borne infections in cattle in
      smallholder dairy farms in Murang'a District, Kenya; a cross-sectional study.
AB  - The most important tick-borne disease of cattle in eastern, central and southern
      Africa is East Coast fever (ECF) caused by Theileria parva and transmitted by the
      tick Rhipicephalus appendiculatus. Other less-important tick-borne diseases in
      cattle are benign theileriosis caused by Theileria mutans, babesiosis caused by
      Babesia bigemina, anaplasmosis caused by Anaplasma marginale and cowdriosis
      caused by Cowdria ruminatum. In Murang's District, Central Province of Kenya,
      five agroecological zones (AEZs) are defined according to climate, altitude and
      agricultural activities. A cross-sectional serological study was conducted on 750
      smallholder dairy farms in Murang's District, selected in a stratified random
      sampling method. The farms had a total of 362 calves. One hundred and fifty farms
      were studied from three administrative sublocations in each of the five AEZs.
      Prevalence of serum antibodies to three tick-borne parasites, that is T. parva,
      T. mutans and B. bigemina, were determined using the enzyme-linked immunosorbent
      assay (ELISA) technique. Antibody prevalence values differed across the AEZs. The
      ranges of means for the prevalences were: T. parva (18-72%), T. mutans (1.5-28%)
      and B. bigemina (12-49%). The above results serve as indicators of the possible
      existence of endemic stability in some AEZs for some parasites.

PMID- 9234415
TI  - Application of composite estimation in studies of animal population production
      with two-stage repeated sample designs.
AB  - This paper reports results from two example data sets of a two-stage sampling
      design where sampling (in panels) both farms and animals within selected farms
      increases the efficiency of parameter estimation from measurements recorded over
      time. With such a design, not only are farms replaced from time-to-time but also
      animals subsampled within retained farms are subject to replacement. Three
      general categories of parameters estimated for the population (the set of animals
      belonging to the universe of farms of interest) were (1) the total at each
      measurement occasion; (2) the difference between means or totals on successive
      measurement occasions; (3) the total over a sequence of successive measurement
      periods. Whereas several responses at the farm level were highly correlated over
      time (rho 1), the corresponding animal responses were less correlated over time
      (rho 2)-leading to only moderate gains in relative efficiency. Intraclass
      correlation values were too low in most cases to counteract the overall negative
      impact of rho 2. In general, sizeable gains in relative efficiency were observed
      for estimating change-confirming a previous result which showed this to be true
      provided that rho 1 was high (irrespective of rho 2).

PMID- 9234416
TI  - Economic evaluation of national identification and recording systems for pigs in
      Belgium.
AB  - Four national identification and recording (I&R) systems for the Belgian pig
      industry were evaluated economically, using a computer simulation model. These
      systems were: (1) the previous system; (2) a revised system (based on the
      previous one); (3) a system based on electronic identification; (4) a system
      similar to (3) but which also allows electronic monitoring of individual pigs.
      The evaluation of the systems particularly concerned their use in the control of
      classical swine fever (CSF). Four factors have shown to be very influential in
      economic decision making with respect to I&R systems: (1) the economic losses per
      CSF epidemic; (2) the frequency of CSF epidemics; (3) the operational costs of
      the I&R system; (4) the possibility of additional use of the system besides CSF
      control. It was concluded that for the Belgian situation, replacement of the
      previous I&R system by the revised one is economically justifiable. Because of
      high operational costs, electronic identification systems are only economically
      feasible in very specific situations, e.g. when a higher degree of additional use
      is possible or with a relatively high frequency of CSF epidemics.

PMID- 9234417
TI  - Economic evaluation of bovine brucellosis and tuberculosis eradication programmes
      in a mountain area of Spain.
AB  - We applied social cost-benefit analysis to the economic evaluation of the bovine
      brucellosis and bovine tuberculosis eradication programmes carried out by the
      public eradication authority for mountain areas in the Spanish Central Pyrenees.
      We considered only the effects on animal health and production. We also evaluated
      several hypotheses corresponding to the different sanitary situations of two
      valleys studied. The results were different for the two disease programmes. The
      brucellosis programme was economically efficient over a sufficiently long time
      frame, but the bovine tuberculosis programme was not. A factor having the
      greatest influence on the economic efficiency of the programmes was the initial
      prevalence of the disease in the two valleys studied. The greater this was, the
      more difficult it was to obtain positive net benefits; this was due the initially
      high compensation paid for the slaughter of animals testing positive for the
      disease. The relatively small animal health and production returns derived from
      the tuberculosis programme explained it's failure to generate positive economic
      results. The fact that the economic evaluation resulted in unfavourable outcomes
      is not in itself justification for project termination, because the benefits to
      the wider community through the prevention of zoonosis were not considered in
      this analysis.

PMID- 9234418
TI  - Cross-sectional estimation of Babesia bovis antibody prevalence in an area of
      Argentina used for extensive cattle breeding as an aid to control babesiosis.
AB  - The prevalence of Babesia bovis antibodies was estimated by using an ELISA (98%
      sensitivity and 95% specificity). Sera were obtained from 165 calves (mean age
      and standard deviation: 9.7 +/- 2.7 months) from an area in Argentina known to be
      unfavourable for the development of the vector tick, Boophilus microplus. The
      area comprised about 300,000 ha used for cattle breeding. The cattle population
      of 55,000 included 12,000 cattle under 1 year of age. Cattle were maintained
      mainly on natural grasses in communal lands. The true prevalence of antibodies to
      Babesia bovis was 12.2% with a confidence interval of 7.6% to 18.2%, and an
      inoculation rate (h; daily probability of infection) of 0.0004. This confidence
      interval has its lower boundary in the area of endemic stability due to low h of
      Babesia bovis by the vector tick and the upper limit in the area of endemic
      instability. This type of analysis could help to decide the implementation of
      preventive measures (e.g. vaccination) rationally, even in remote areas (such as
      the one of the present study) with an extensive cattle industry.

PMID- 9234420
TI  - Survivorship approaches to measuring and comparing cull rates for dairies.
AB  - A study was undertaken to develop the use of survivorship methods in
      characterizing the magnitude of culling and in testing for differences in culling
      among dairy herds. A prospective observational study was conducted on nine herds
      representing 19482 cows. The cull rate derived from survivorship data was
      estimated as the weighted slope of the cumulative proportion of cows remaining in
      a herd after first parturition, where cumulative proportion was computed using a
      cohort life-table with intervals of 1 month. Cull rates ranged from 9.0-13.8% per
      12 months of age, compared with culling density rates of 22.2-39.7 culled per 100
      cow-years. Comparison of ranks of density rates, weighted-slope rates and median
      ages at culling among the herds illustrated that the measures were not
      interchangeable. An advantage of a survivorship approach to measuring culling was
      illustrated by the use of the Cox proportional hazards model that tested for
      differences in cull rates among herds. Results suggested that variation in
      culling among herds during the first lactation, and particularly during the first
      part of the first lactation, may be an important consideration in future studies
      of optimal culling practices. In addition to being able to compare culling among
      herds, a survivorship approach to measuring culling provides an estimate of the
      rate of removal that is not biased by age, in contrast to currently used methods.

PMID- 9234419
TI  - Effect of ewe ovine lentivirus infection on ewe and lamb productivity.
AB  - We used a previously described sensitive and specific ovine lentivirus (OLV)
      recombinant transmembrane (rTM) protein enzyme-linked immunosorbent assay (ELISA)
      to detect anti-OLV antibodies and define OLV infection in breeding ewes from nine
      US Meat Animal Research Center (MARC) flocks. We estimated the production impacts
      of dam rTM ELISA seropositivity on ewe and lamb productivity in the birth-to
      weaning interval using production data from 1466 breeding ewes (of which 1242
      actually lambed) and their 2452 lambs born in spring 1992 using several multiple
      linear and logistic regression models. By adjusting for lamb weaning age, gender,
      type of birth and rearing, birth difficulty, dam age, and flock, the component of
      ewe or lamb productivity related to ewe OLV infection alone was isolated. The rTM
      ELISA-negative ewes produced significantly more total weight of weaned lamb per
      ewe-lambing (3.84 kg) and per ewe ram-exposed (4.95 kg) compared to their OLV
      positive flockmates. Negative ewes also weaned 0.11 more lambs per ewe-lambing
      and 0.09 more lambs per ewe ram-exposed, gave birth to 0.13 more lambs per ewe
      ram-exposed, and were more likely to lamb after breeding (odds ratio (OR) = 1.9)
      compared to equivalent OLV-positive ewes. Lambs reared by OLV-negative ewes
      weighed 0.15 kg more at birth, gained 8 g more per day through weaning, and
      weighed 0.59 kg more at 56-day weaning. Preweaning mortality was lower (OR = 0.8)
      among lambs born to OLV-negative compared to OLV-positive ewes, although this
      difference was not significant. Our results suggest that subclinical OLV
      infection has important detrimental effects on sheep production which occur in
      cumulative fashion from breeding through weaning and that OLV control efforts may
      be financially justified in some sheep flocks.

PMID- 9234421
TI  - Design and implementation of the United States National Animal Health Monitoring
      System 1994-95 Cattle on Feed Evaluation, and an evaluation of the impact of
      response biases.
AB  - The 1994-95 Cattle on Feed Evaluation was a cooperative project (sponsored by the
      United States Department of Agriculture) involving Washington State University,
      state agricultural departments, and several agencies of the United States
      Department of Agriculture). The project focused on cattle-on-feed operations in
      13 states that accounted for over 85% of the United States cattle on feed
      inventory. Participants were selected from National Agricultural Statistics
      Service list frames. Questionnaires were administered by telephone to operations
      with a one-time capacity of fewer than 1000 cattle; larger operations were
      visited twice to administer questionnaires. The participation rate for the first
      phase of the study was 56.7%. Ninety-one percent of eligible operations completed
      the second phase of the study. Data summarized from this national study can be
      used to profile management practices on cattle-feeding operations in the United
      States. Differences between participants and non-participants did not appear to
      be great. However, one does need to be mindful of the fact that a small
      percentage of the producers accounted for the vast majority of feedlot cattle
      marketed when interpreting the results.

PMID- 9234422
TI  - Issues concerning Mexican cattle on feedlots in the United States as reported in
      the United States National Animal Health Monitoring System 1994-1995 Cattle on
      Feed Evaluation.
AB  - Producers participating in the United States National Animal Health Monitoring
      System 1994-1995 Cattle on Feed Evaluation provided information on cattle of
      Mexican origin in their feedlot operations. Cattle of Mexican origin accounted
      for 8.1% of cattle placed on United States feedlots from 1 July 1993 through 30
      June 1994. Of operations with a one-time capacity of 1000 or more cattle, 12.8%
      placed cattle of Mexican origin on their feedlots over this time frame. Very few
      operations (about 1%) reported cattle of Mexican origin at the same time as
      cattle to be used for breeding in the United States.

PMID- 9234423
TI  - A processing plant survey of external lesions of American eels (Anguilla
      rostrata) from Lake Ontario and the St. Lawrence River, Canada.
AB  - Signs of decreasing landing and recruitment were observed in the last decade in
      American eels (Anguilla rostrata) from the St. Lawrence River basin, Canada. In
      order to verify if the declines were associated with high prevalence of diseases
      among commercial catches, a total of 12243 eels captured in five commercial
      fishing sites were inspected at two processing plants in 1992. They were all
      examined for external lesions and palpated to detect vertebral deformities. Eels
      from Lakes Ontario, Saint-Francois and Saint-Pierre were mainly resident eels,
      while those from the Richelieu River and the St. Lawrence Estuary at Kamouraska
      were mainly mature migrating eels. Prevalences of every lesion observed were low
      (< or = 1%) at every site. Scratches all over the body were found only on eels
      from Kamouraska. Cutaneous ulcers were observed more frequently in the Richelieu
      River. Higher prevalences of vertebral deformities were found in mature migrating
      eels captured in Kamouraska and in the Richelieu River. Vertebral deformities
      were also observed more frequently among eels captured at the end of the 1992
      fishing season in Kamouraska. Higher length, weight and/or age of mature
      migrating eels may be associated with higher prevalences of vertebral deformities
      among this group. These results do not indicate that the health of the American
      eels commercially captured in the St. Lawrence basin is severely impaired.
      However, the magnitude of diseases among the biological population is probably
      underestimated by such a survey.

PMID- 9234424
TI  - A telephone survey of eel fishermen regarding external lesions and mortalities of
      American eels (Anguilla rostrata) from Lake Ontario and the St. Lawrence River
      basin, Canada.
AB  - Signs of decreasing landings and recruitment have been observed during the last
      decade in American eels (Anguilla rostrata) from the St. Lawrence River basin,
      Canada. A study was undertaken to examine whether important manifestational
      diseases among commercial catches could be associated with these declines. During
      this survey, 56 fishermen from Lakes Ontario, Saint-Francois and Saint-Pierre,
      the Richelieu River, the Quebec City area and the St. Lawrence Estuary were
      interviewed. Most fishermen from every area reported decreasing catches since the
      1980s. Eel mortalities were reported from 1990 to 1992 in Lake Saint-Francois,
      Lake Saint-Pierre and the Quebec City area, but in apparently lower magnitude
      than in the past decades. The lesions observed on dead eels in Lake Saint
      Francois indicated that the cause of the mortalities might be associated with the
      upstream hydroelectric dam. Eels with 'scratches all over the body' were only
      observed in the St. Lawrence Estuary. Fishermen from almost every area reported
      that they had observed eels with 'crooked tail', 'humpback' and 'cut tail' in low
      frequency in 1992. The questionnaire data were validated by comparing some of the
      results of the questionnaire survey and a processing plant survey in 1992. The
      use of questionnaires for assessing fish diseases in commercial species is
      discussed. The results of this survey do not indicate that the health of the
      American eels from the St. Lawrence River basin is severely impaired. However,
      the magnitude of diseases and mortalities was probably underestimated.

PMID- 9234425
TI  - Estimated prevalence of paratuberculosis in Missouri, USA cattle.
AB  - An absorbed ELISA for detection of antibodies against Mycobacterium
      paratuberculosis was performed on serum samples obtained from the Missouri Animal
      Health Laboratory. Samples from 1954 Missouri cattle representing 89 herds were
      randomly selected from samples submitted for brucellosis testing. The apparent
      seroprevalence of paratuberculosis in dairy cattle (8 +/- 3%) was similar to that
      in beef cattle (5 +/- 2%). When herds were classified as dairy or beef, 74% (14
      of 19) of dairy herds and 40% (27 of 68) of beef herds were positive.

PMID- 9234426
TI  - The association of serum nonesterified fatty acids and cholesterol, management
      and feeding practices with peripartum disease in dairy cows.
AB  - A prospective study was conducted to determine the relationship of serum
      nonesterified fatty acids (NEFA) and cholesterol concentrations and herd
      management practices to the occurrence of metritis, mastitis and retained
      placenta in Holstein cows in Michigan. Serum samples were collected once
      prepartum and once postpartum from 257 cows. Animals were under observation for
      disease occurrence from the date of calving until 3 months postpartum. Metabolic
      variables used were (1) prepartum only; (2) postpartum only; (3) the
      NEFA/cholesterol ratio for both pre- and postpartum samples. Management variables
      included maternity management, feed management, and factors such as season and
      parity. Multivariable logistic models with random-effect terms to account for the
      herd effect were used for data analysis. Results showed that: (1) metabolic
      events associated with energy insufficiency-increased fat mobilization and serum
      lipoprotein metabolism-were related to increased risk of metritis and retained
      placenta; (2) higher energy consumption during the last weeks of the dry period
      might reduce disease risk at parturition; (3) serum NEFA and cholesterol
      concentrations have potential as indicators of disease risk in dairy cows.

PMID- 9234427
TI  - Validation of a poultry biosecurity survey.
AB  - A questionnaire for farm managers was designed, to obtain information regarding
      biosecurity on Ontario commercial broiler chicken and turkey operations, and then
      pre-tested. The questions that could be validated were verifiable by seeing the
      facility, by using farm records or by interviewing technical personnel other than
      the survey respondent. The survey was validated using a convenience sample of 24
      farms from two companies. For 15 questions with dichotomous responses, the
      sensitivity ranged from 16.7 to 100%; the specificity ranged from 0 to 100%. For
      example, fences and gates seen during the farm visit were not accurately reported
      on the survey (poor sensitivity). Chance-corrected agreement was low (kappa <
      0.4) for 34 questions, fair to good (0.4 < kappa < 0.8) for 25 questions, and
      excellent (kappa > 0.8) for seven questions. The percent agreement for questions
      where only one of the possible options was observed on validation ranged from
      60.9 to 100%. Five questions with continuous numeric variables were analysed. A
      difference was observed (P < 0.1) between the survey and validation data for
      three questions regarding the number of birds, the bird sources and the downtime
      between flocks. In spite of pre-testing, the lack of clear wording and the
      absence of definitions for technical terms appeared to reduce validity. Response
      bias seems to be an issue with biosecurity surveys. The value of validating
      questionnaires before their use in epidemiologic research is confirmed.

PMID- 9234429
TI  - Avoparcin used as a growth promoter is associated with the occurrence of
      vancomycin-resistant Enterococcus faecium on Danish poultry and pig farms.
AB  - We determined the association between the use of the glycopeptide antibiotic
      avoparcin as a growth promoter and the occurrence of Enterococcus faecium (VREF)
      with high-level resistance to vancomycin (MIC > or = 64 micrograms ml-1) on
      poultry and pig farms. The investigations were conducted as retrospective cohort
      studies, where groups of farms exposed or not exposed to avoparcin between
      September 1994 and April 1995 were compared. In poultry, the association between
      the use of avoparcin and the occurrence of VREF was confounded by the use of
      broad-spectrum antibiotics, and the adjusted relative risk was 2.9 (1.4-5.9). In
      pigs, the association had a similar magnitude with a non-adjusted relative risk
      of 3.3 (0.9-12.3). The similar findings in the two studies provide evidence in
      favour of a causal association between the use of avoparcin and the occurrence of
      VREF on farms, and suggest that food animals constitute a potential reservoir of
      infection for VREF in humans.

PMID- 9234428
TI  - Leptospira interrogans serovar icterohaemorrhagiae seropositivity and the
      reproductive performance of sows.
AB  - The reproductive performance of 28 sows seropositive to Leptospira interrogans
      serovar icterohaemorrhagiae was compared with that of 87 Leptospira sp.
      seronegative dams belonging to the same herd. Sows were sampled during 1988 to
      1993. During this period the herd was not submitted to any kind of intervention
      (antibiotic therapy, immunoprophylaxis or rodent control). Relative risks (RR) of
      return to heat, mummified fetuses, stillbirth, and weak newborn piglets for
      infected sows were assessed and the differences in means of total piglets born
      per litter, piglets born alive, piglets effectively housed, weaned piglets,
      stillbirths, mummified fetuses, weak newborn piglets, weight at birth of the
      piglets effectively housed, weight at 21 days of life and weight at weaning were
      evaluated. Seropositive dams had a greater risk of having weak newborn piglets
      (RR = 1.67, 1.02 < or = CI 95% < or = 2.72) and also of having more weak newborn
      piglets per litter (P = 0.01). Other variables examined were not different (P >
      0.05).

PMID- 9234430
TI  - The association between the bovine tuberculosis status of herds in the East
      Offaly Project Area, and the distance to badger setts, 1988-1993.
AB  - The proximity of farms to badger setts was compared between farms that had
      experienced a tuberculosis breakdown and those that had not, over the 6 year
      period from 1988 to 1993. The data were derived from a badger removal study
      conducted in East Offaly County in the Republic of Ireland. Badger removal began
      in 1989 and continued through 1993; by the end of 1990, approximately 80% of all
      badgers caught in the 6 year period had been removed. All badgers were examined,
      grossly, for evidence of tuberculosis. Tuberculosis status of the approximately
      900 study herds was based on the results of the single intradermal comparative
      skin test and/or lesions of bovine tuberculosis. All herds were tested at least
      once annually. The number of herds experiencing bovine tuberculosis declined over
      the period, particularly in the years 1992 and 1993. The data on farm and badger
      sett location were stored and analysed, initially, in a geographical information
      system. Owing to the badger removal programme, the distance between the barn yard
      of a typical farm and the nearest occupied badger sett increased, by about 300 m
      year-1, and by about 600 m year-1 to the closest infected sett. In bivariate
      analyses, in the years 1988 and 1989, the risk of tuberculosis declined with
      increasing distance to a badger sett containing one or more tuberculous badgers.
      In multivariable logistic regression analyses, year and the average number of
      cattle tested per farm per year were controlled. A second identical analysis was
      conducted to control for the repeated observations on the same herds using
      generalised estimating equations. In both analyses, the risk of a multiple
      reactor tuberculosis breakdown decreased for herds at least 1000 m away from an
      infected badger sett, and increased as the number of infected badgers per
      infected sett increased. Despite the significantly reduced risk of a breakdown
      with increasing distance to infected badger setts, the relationship was not
      strong (sensitivity and specificity of the model in the low 70% range) and
      explained only 9-19% of tuberculosis breakdowns.

PMID- 9234431
TI  - Seroprevalence of Borrelia burgdorferi in dogs in Alabama, USA.
AB  - A random sample of private small-animal practices in Alabama submitted sera from
      dogs with known tick contact. A total of 579 samples from the three geographic
      regions of the state were collected (58% of the targeted sample size). Sera were
      screened for antibodies to Borrelia burgdorferi using an indirect fluorescent
      antibody (IFA) test which had a sensitivity and specificity of greater than 90%.
      Anti-B burgdorferi titers of > or = 1:64 were considered to be positive, based on
      results from B. burgdorferi-inoculated dogs. Ten of the 579 samples (1.7%) were
      positive, and titers ranged from 1:64 to 1:512. Seropositive dogs were found
      throughbout the state, and there was no significant difference in seroprevalence
      by region (Mantel-Haenszel chi 2, P = 0.85). These results indicate that the
      seroprevalence for canine Lyme disease in Alabama is low and that use of the
      canine Lyme disease vaccine is not justified.

PMID- 9234432
TI  - Associations between off-label feed additives and farm size, veterinary
      consultant use, and animal age.
AB  - Data from the United States National Swine Survey collected by the National
      Animal Health Monitoring System were used to describe the use of feed additives
      in swine feeds. Data were collected from 710 farms. The concentration of feed
      additives expressed in grams per ton of complete feed was described by stage of
      production, and the use of feed additives above the labeled treatment levels
      (i.e. off-label) was identified. Of the 3328 feeds, about 79% contained feed
      additives used in the labeled manner. For all classes of pigs, the prevalence of
      labeled feed additive use was greater than 75%. Penicillin was used according to
      its label most often, followed by apramycin, bacitracin, tetracyclines,
      lincomycin, and tylosin. Carbadox had the highest prevalence of off-label use. Of
      the 699 feeds that included feed additives in an off-label manner, about 57%
      included additives at greater than the recommended concentrations or were fed to
      an incorrect class of pig. About 56% of the feeds had off-label combinations of
      additives. Small farms were more likely to use rations with no feed additives
      than intermediate or large farms (P < 0.001). Of those farms using feed
      additives, the odds of a small farm using all feed additives in the labeled
      manner was 7.7 times that of an intermediate or large farm (P < 0.0001). After
      controlling for herd size, producers who used a veterinary consultant were 2.1
      times more likely to use feeds with feed additives (P < 0.0001).

PMID- 9234433
TI  - Intra-cluster correlation coefficients of 20 infections calculated from the
      results of cluster-sample surveys.

PMID- 9234434
TI  - Nation-wide Salmonella enterica surveillance and control in Danish slaughter
      swine herds.
AB  - A nation-wide Salmonella enterica surveillance and control programme was
      initiated in Danish finishing herds over the first quarter of 1995. In Denmark,
      all swine for slaughter are identifiable by a unique herd code. For each herd
      code, and depending on the herd's annual kill, random samples ranging from four
      to more than 60 swine are obtained quarterly at the abattoir. A meat sample from
      each pig is frozen, and meat juice (harvested after thawing) is examined for
      specific antibodies against S. enterica using an indirect enzyme-linked
      immunosorbent assay (ELISA). The ELISA combines several S. enterica O-antigens,
      and allows detection of antibody response after a variety of different S.
      enterica serovar infections. Results are transferred to a central database, which
      each month (based on meat-juice tests obtained in the previous 13 weeks) assigns
      all herds into three S. enterica infection levels: Level 1, in which the S.
      enterica prevalence is deemed low and acceptable; Level 2, where there is a
      moderate prevalence of S. enterica seroreactors (from > 50% in the smallest to >
      10% in the largest herds); Level 3, in which S. enterica seroreactor prevalence
      is clearly unsatisfactory (> 50% for most herd sizes). Irrespective of Salmonella
      level, all herds receive a monthly update on the current results of the S.
      enterica test results. If a herd is categorized in Level 2 or 3, it must receive
      an advisory visit by a practising veterinarian and a local swine extension
      specialist, and certain management hygiene precautions must be taken. If a herd
      is categorized in Level 3, the finishers from the herd must additionally be
      slaughtered under special hygiene precautions. This is supervised by the
      veterinary authorities. During 1995, 604000 samples were tested for S. enterica,
      corresponding to 3.0% of the total kill. In December 1995, 15522 herds
      (representing > 90% of the national production) were categorized into one of the
      three levels: 14551 herds (93.7%) in Level 1; 610 herds (3.9%) in Level 2; 361
      herds (2.3%) in Level 3. The proportion of serologically positive meat-juice
      samples collected during 1995 ranged from a mean of 2.9% in smaller herds (101
      200 swine slaughtered per year) to 6.1% in relatively large herds (more than 5000
      swine slaughtered per year).

PMID- 9234435
TI  - The Michigan equine monitoring system. I. Design, implementation and population
      estimates.
AB  - The Michigan equine monitoring system (MEMS) was designed and implemented in the
      State of Michigan, starting in 1991. The program was designed systematically to
      track the State's equine population, its health, and its economic implications to
      the equine industry. The MEMS was designed as a two-phase program. Phase I (the
      population and economic survey; the subject of this paper) was designed to
      provide new and statistically valid information describing the size, composition,
      location and economic characteristics of the Michigan equine industry. A
      standardized questionnaire was used to collect data via mail, telephone and
      personal interviews. Of the 3000 randomly selected list-frame samples, 2800 (93%)
      participated. However, 650 of these had no equids. There were 129,932 equids
      reported compared with 160,000 in 1984. The American Quarter Horse, Standardbred
      and Arabian breeds were the most numerous. Detailed results, including the size
      of equine operations/herds, uses, geographical distribution and the financial
      structure of the industry, are presented. A detailed account of the strategies
      used in designing and implementing the system is provided.

PMID- 9234436
TI  - The Michigan equine monitoring system. II. Frequencies and impact of selected
      health problems.
AB  - A prospective study was designed to document the frequencies of equine health
      problems in the state of Michigan, USA. A total of 2469 horses from a random
      sample of 138 equine operations were monitored in the study in two 12-month
      periods: 1992-1993 and 1993-1994. All the major breeds of horses in the state
      were proportionately represented in the sample. Using weighted annual incidence
      densities as measures of disease frequencies, the 10 most frequently observed
      groups of health problems were (from most to least frequent) leg lameness,
      dermatological problems, respiratory problems, hoof and foot problems,
      reproductive problems, systemic problems, colic, whole body lameness,
      neurological problems and gastrointestinal problems (other than colic). This
      ranking of the top 10 health problems was different from the ranking provided by
      equine owners/operators at the beginning of the study. Overall, very low specific
      mortality rates were observed in the study. However, the conditions that were
      associated with mortality resulted in fairly high case fatalities. The five
      specific illnesses that most commonly resulted in fatalities were (from greatest
      to least case fatality risk) systemic problems, colic, gastrointestinal problems
      (other than colic), neurological problems, and foot and hoof problems. Impact of
      disease was evaluated in terms of average duration of a case and days lost for
      performance. Neurological problems, lameness and dermatological problems had the
      longest duration per case. Neurological problems, lameness, respiratory problems
      and gastrointestinal problems (other than colic) had the longest average days
      lost per case.

PMID- 9234437
TI  - Bluetongue virus seropositivity in sheep flocks in North West Frontier Province,
      Pakistan.
AB  - The objectives of this study were to describe the prevalence and distribution of
      serum antibodies to Bluetongue virus (BTV) in a sample of 38 sheep flocks in
      northern areas of the North West Frontier Province of Pakistan and to identify
      demographic and productivity variables that are associated with BTV
      seropositivity. Blood samples were taken from a random sample of ewes in each
      flock in April 1995. The owners of the flocks were interviewed regarding some
      demographic, husbandry and productivity variables of the flocks on the day of
      blood sampling. A competitive enzyme-linked immunosorbent assay was conducted to
      test the serum samples for BTV group-specific antibodies. BTV seropositive
      reactions were obtained in 184 (48.4%) out of 380 tested sera, and in 89.5%
      (34/38) of the flocks. In the 34 seropositive flocks, the prevalences ranged from
      12.5 to 100% (median = 47). A multivariable logistic analysis was carried out to
      study the influence of demographic and productivity variables on the BTV
      serological status of the sheep flocks. Abortion risk in the previous lambing
      season was mildly associated with the serological status of the flock (adjusted
      odds ratio = 1.16, P = 0.07). For the seropositive flocks, a linear multiple
      regression showed that distance travelled by the flock during transhuman movement
      was significantly associated with percent seropositivity (partial regression
      coefficient (+/- SE) = -0.091 +/- 0.045).

PMID- 9234438
TI  - Simulation analysis of the effect of herd immunity and age structure on infection
      of a cattle herd with bluetongue viruses in Queensland, Australia.
AB  - A state-transition model based on Leslie matrix formulation was used to
      investigate the effects of herd immunity and age structure on the infection of a
      simulated cattle herd with bluetongue viruses under Australian climatic
      conditions. Increasing duration of immunity decreased the prevalence of
      infection. A duration of immunity of 33 months was consistent with prevalence
      estimates made from previous serological studies of bluetongue virus. Herd
      prevalence displayed slowly dampening cyclical variation over time (most
      pronounced when a short duration of immunity was simulated). Increasing calving
      and mortality risk rates in the simulated herd increased prevalence, whereas
      increasing age at first calving decreased prevalence. Manipulation of calving
      rates had the greatest effect on the predicted prevalence of infection in the
      herd. Simulation of a number of herd-management scenarios suggested that
      management systems in which cattle are bred early and where high calving rates
      are achieved are likely to contribute to high levels of infection with bluetongue
      viruses. Results confirm the importance of management factors in influencing the
      prevalence of infectious diseases in animal populations.

PMID- 9234439
TI  - Agricultural policy and social returns to eradication programs: the case of
      Aujeszky's disease in Sweden.
AB  - Economic-welfare analysis of animal disease prevention programs frequently ignore
      the constraints of the agricultural policy environment. Prevention programs
      affect producers, consumers and the government. The policy environment to a large
      extent determines the magnitude as well as the distribution of benefits of the
      program among these groups. The Swedish hog industry has been exposed to three
      major policy changes during the 1990-1995 period. These scenarios involve various
      degrees of government intervention in the agricultural sector including internal
      market deregulation and EU-membership. Aujeszky's disease is a virus disease with
      swine as the natural infection reservoir. Piglets are the most fragile and an
      outbreak of the disease results in symptoms such as shaking, cramps and
      convulsions with an increase in the mortality rate. Slaughter hogs suffer from
      coughing, fever and reduce their feed consumption. During the last 20-25 years
      the incidence of Aujeszky's disease (AD) has been increasing in Sweden. In 1989
      an eradication program was undertaken. A model is developed to analyze social
      benefits of an eradication program given variations in agricultural policy. The
      model refers to the specifics of the AD-program implemented in Sweden. The
      expected benefits of the program are evaluated using a welfare-economic analysis
      applying cost-benefit analysis. Total benefits of the program are evaluated
      across herd and size categories and different regions. Data concerning the
      frequency of the virus among various categories of herds prior to enacting the
      program were used (Wahlstrom et al., 1990). In addition, data from an
      agricultural insurance company were used to estimate the conditional probability
      of an outbreak given that the herd is infected. Biological and technical
      parameter values were collected from a variety of sources. The results of the
      analysis indicate that the program is economically viable given a social rate of
      discount in the range of 3-5% without considering non-monetary aspects such as
      animal ethics. A scenario where the Swedish agricultural sector is deregulated
      provides the maximum benefits of the program. Consumers obtain about 50% of the
      benefits excluding program costs. The deregulation scenario would correspond
      closely to a case where a reformed Common Agricultural Policy (CAP) is applied
      across member countries. In the current case where Sweden is a member of the EU,
      the benefits are reduced mainly due to lower prices of inputs and pork.

PMID- 9234440
TI  - Rearing conditions and foot-pad dermatitis in Swedish broiler chickens.
AB  - A method of classification of broiler foot-health status was developed to
      estimate the prevalence of foot-pad dermatitis in Swedish broilers. Data on foot
      health were collected from 101 commercial broiler flocks at slaughter. The
      producers were asked to fill in a questionnaire on rearing conditions and
      equipment for every flock. Lesions were commonly observed; only 62% of the birds
      were classified as being without lesions, 32% had mild lesions only
      (discoloration, erosions) and 6% had severe lesions (ulcers). Flocks reared in
      houses equipped with small water cups had significantly (P < 0.05) higher
      prevalences of foot-pad dermatitis than flocks reared with water nipples. Thick
      layers of litter, regardless of litter material, also resulted in significantly
      (P < 0.05) higher prevalences of foot-pad dermatitis than litter layers thinner
      than 5 cm.

PMID- 9234441
TI  - Incidence and risk factors for bumblefoot (pododermatitis) in rehabilitated
      raptors.
AB  - A retrospective cohort study was conducted on 821 raptors of 12 representative
      species, admitted to the California Raptor Center (CRC), during 1980-1990. The
      incidence rate for bumblefoot was 52 cases per 100 bird-years at risk. Eagles and
      hawks (buteos) were more likely to develop bumblefoot, and did so earlier during
      their captivity than other species. Also, raptors admitted with a limb fracture
      had the greatest risk (OR = 4.2) of developing bumblefoot than any other
      condition on entry. Median time from admission to development of bumblefoot was
      52 days, and median duration of bumblefoot was 23 days.

PMID- 9234442
TI  - Prevalence of Cryptosporidium spp. oocysts in cattle and wildlife in Morogoro
      region, Tanzania.
AB  - Prevalences of Cryptosporidium spp. oocysts in cattle (n = 486) on five selected
      farms in Morogoro municipality and three species of herbivorous wildlife (n = 87)
      from Mikumi National Park, Morogoro, Tanzania, were determined using the modified
      Ziehl-Neelsen staining technique. Of 486 bovine faecal samples, 5.3% were
      positive for Cryptosporidium spp. The prevalence of Cryptosporidium was higher in
      calves less than 3 months of age compared to weaned calves and adults.
      Cryptosporidium spp. oocysts were detected in both diarrhoeic and non-diarrhoeic
      animals, but there was a significantly higher prevalence (P < 0.001) of oocyst
      shedding in diarrhoeic than in non-diarrhoeic animals. Of the 87 faecal specimens
      from the wildlife species, 36 were from the African buffaloes (Syncerus caffer),
      25 from zebra (Equus zebra) and 26 from the wildebeest (Connochaetes gnou).
      Cryptosporidium spp. oocysts were detected in eight (22%) buffaloes, seven (28%)
      zebras and seven (27%) wildebeests. Confirmation of the diagnosis was performed
      using anti-Cryptosporidium monoclonal antibody specific for Cryptosporidium
      muris. Cryptosporidium parvum and Cryptosporidium baileyi (Pathasure
      Cryptosporidium test kit).

PMID- 9234443
TI  - Eimeriosis in dairy cattle farms in Morogoro municipality of Tanzania.
AB  - Coccidial oocysts were detected in 35% of 445 cattle in four medium-scale and 20
      small-scale dairy farms in Morogoro municipality, Tanzania. The highest
      prevalence (56%) was observed in animals aged between 5 and 18 months, whereas
      lower prevalences were observed in calves (29%) aged between 12 days and 4 months
      and adults (30%). No coccidial oocysts were detected in calves less than 12 days
      old. The oocyst output was high in calves, followed by weaners; adults had the
      lowest oocyst output. The number of oocysts per gram of faeces was significantly
      higher (P < 0.001) in diarrhoeic animals than in non-diarrhoeic animals, and more
      so in young calves. Eimeria species infecting the animals included Eimeria bovis
      (68%) and Eimeria zuernii (57%), Eimeria ellipsoidalis (25%), Eimeria cylindrica
      (23%), Eimeria auburnensis (22%), Eimeria alabamensis (12%) and Eimeria
      subspherica (5%). Mixed infections involving two or three species were common.
      Our findings indicate that eimeriosis is common in cattle in Morogoro
      municipality.

PMID- 9234444
TI  - The use of a mass-action model to validate the output from a stochastic
      simulation model of bovine viral diarrhoea virus spread in a closed dairy herd.
AB  - The spread of bovine virus diarrhoea virus (BVDV) in a closed dairy herd
      maintained under typical management conditions is studied using two approaches.
      In the first instance a stochastic computer model is used to simulate the month
      to-month changes in the infection status of each animal. These results are
      contrasted with the results of a mass-action model which uses three differential
      equations. A comparison of the two approaches indicates that the results are in
      broad agreement. The stochastic approach has the benefit of providing an estimate
      of the probability of the infection becoming extinct and the herd becoming BVDV
      free for different herd sizes.

PMID- 9234445
TI  - Associations between farm management practices, productivity, and bovine leukemia
      virus infection in Ontario dairy herds.
AB  - The objective of this study was to investigate the associations between herd
      level bovine leukemia virus (BLV) status and herd-level management and production
      variables. The study population consisted of 1330 cows sampled from 102 Ontario
      dairy herds. The individual-cow prevalence of BLV infection in the population
      (based on AGID testing) was 23%, with 69.6% of herds having one or more positive
      animals. The herd-level explanatory variables were divided into two datasets
      containing winter housing variables and all non-seasonal variables, and summer
      housing variables and all non-seasonal variables. In both datasets, multivariable
      analyses found a negative association between herd-level milk production and BLV
      status, and positive associations between weaning age and purchasing animals from
      outside sources, and BLV status. Housing pre-weaned calves in hutches or separate
      calf buildings in either season was associated with an increased risk of BLV. The
      model containing winter housing variables also included positive associations
      between contact with older animals and BLV status, and between BLV status and the
      facilities used to house dry cows in the winter.

PMID- 9234446
TI  - Evaluation of a bulk-milk ELISA test for the classification of herd-level bovine
      leukemia virus status.
AB  - The results of a commercial bulk-milk enzyme-linked immunosorbent assay (ELISA)
      test for herd-level bovine leukemia virus (BLV) status were compared to results
      obtained from individual agar-gel immunodiffussion (AGID) testing on sampled
      cattle. A positive herd was defined as a herd having one or more AGID-positive
      animals. The estimated true herd status was based on the sensitivity and
      specificity of the AGID test and the number of cattle sampled per herd. Ninety
      seven herds were used, with a mean of 13 cows sampled per herd. The AGID test
      indicated an apparent herd prevalence of 70.1%. After accounting for the number
      of cows sampled and the sensitivity and specificity of the AGID test, the
      estimated true herd prevalence of BLV was 52.3%. The ELISA test identified 79.4%
      of herds as positive for BLV, and had an apparent sensitivity and specificity of
      0.97 and 0.62, respectively. However, after accounting for the sensitivity and
      specificity of the AGID test in individual animals, the specificity of the ELISA
      test was 0.44. The ELISA test was useful for identifying BLV-negative herds
      (i.e., ruling out the presence of BLV infection in test negative herds). With the
      moderately low specificity, herds identified as positive by the ELISA test would
      require further testing at the individual or herd level to definitively establish
      their BLV status.

PMID- 9234447
TI  - Management and nutritional factors associated with the detection of Salmonella
      sp. from cattle fecal specimens from feedlot operations in the United States.
AB  - In a convenience sample of 100 feedlot operations (included in the United States
      Department of Agriculture: Animal and Plant Health Inspection Service 1994 Cattle
      on Feed Evaluation), up to 25 cattle fecal samples were collected and tested for
      the presence of Salmonella from each of two pens (the pen which contained the
      most-recent arrivals, and the pen with cattle that had been on feed the longest).
      One or more Salmonella spp. were recovered from 38 (38.0%) of the 100 feedlots,
      52 (26.0%) of the 200 pens and 273 (5.5%) of the 4977 fecal samples collected.
      Multivariable logistic regression indicated that feeding tallow and feeding whole
      cottonseed or cottonseed hulls within seven days prior to fecal sample collection
      was associated with an increased risk of finding Salmonella in a pen. Variables
      not found to be significantly associated with the detection of Salmonella in a
      pen included region, operation size, use of sprinklers, time on feed, type of
      cattle in the pen, number and concentration of cattle in a pen, feeding
      probiotics, and various other feeds.

PMID- 9234448
TI  - Epidemiology of bovine abortions in Israeli dairy herds.
AB  - Routine monitoring of abortions is carried out on most Israeli Kibbutz dairy
      herds. The reports include both descriptive epidemiology and multivariable
      analysis. Data are presented according to parity, trimester, abortion curves and
      sire. Results are produced in the form of abortions per 10000 cows-days-at risk,
      proportion of aborted cows by 260 days of gestation, abortion per confirmed
      pregnancy, and adjusted odds ratios. For 58048 pregnancies from 111 herds in
      1995, the respective abortion density, proportion of aborted cows, and abortions
      per confirmed pregnancy were 4.2, 5.9%, and 10.2%. Among parities, heifers had
      the lowest, and cows of second parity the greatest risk of fetal death
      (respective odds ratios 0.6 and 1.3) compared to all other parities pooled
      together. The greatest risk of fetal death was observed in the first, and the
      lowest in the second trimesters of pregnancy (odds ratios 1.9 and 0.6,
      respectively). Recurrent risk ratio for abortion in the same lactation was high
      (odds ratio 2.7). Respective proportions of aborted cows with and without a
      previous abortion were 17.5% and 5.9%. Odds of aborting after twinning in
      multiparous cows was 1.3 greater than for those having a single calf. Risk of
      abortion in the autumn and early winter was greater than that in the summer
      months. Increased risks of abortion were associated with eight sires out of the
      233 used (odds ratios of mates to abort ranged from 1.9 to 3.9). One, two and
      three peaks of abortions were established in 53.2%, 24.3%, and 0.9% of the 111
      herds studied in 1995. None were detected in 21.6% of the herds.

PMID- 9234449
TI  - Immune response following a vaccination campaign against rabies in dogs from
      northwestern Spain.
AB  - A cross-sectional study was carried out to determine the seroprevalence of
      antibodies to the rabies virus in 156 vaccinated dogs from two provinces in the
      Castilla y Leon Autonomous Community (northwest Spain). An obligatory anti-rabies
      programme is currently in place in this region. Seroprevalence was established by
      an indirect enzyme-linked immunosorbent assay. Of the 156 animals tested, 91
      (58.3%) were positive (titres of 0.5 IU ml-1 or above). However, Soria province
      showed a significantly higher seroprevalence (77.1%) than Leon province (50%).
      Age, sex, habitat and use were evaluated with regard to the response obtained
      after vaccination: no significant differences were discovered for any of these
      factors. However, guard and herding dogs in Leon province tended to have lower
      seroprevalence than dogs not used in these ways. In general, there is a limited
      response to the vaccination programme in dogs from Castilla y Leon-especially in
      Leon province.

PMID- 9234450
TI  - The relationship of calfhood morbidity with survival after calving in 25 New York
      Holstein herds.
AB  - The association of owner-diagnosed calfhood diseases with the length of herd life
      after calving was evaluated using data collected prospectively over a ten-year
      period in 25 New York Holstein dairy herds. Herds selected for the study were
      milking between 35 and 200 Holstein cows, used dairy herd improvement records,
      bred cows by artificial insemination unless they needed three or more services,
      and had regularly-scheduled herd health visits by clinicians from the Cornell
      University College of Veterinary Medicine. Owners recorded occurrences of
      dullness, respiratory disease, and scours from birth through 90 days of age for
      all heifer calves that lived at least 24 h and were to be kept as replacements.
      Milking herd life was measured as the difference between the age at first calving
      and the age at death or sale. Data on cows sold when the herd went out of
      business or still in the herd at the end of the study were censored observations.
      Cox's proportional hazards model was used for statistical analysis of the data.
      Controlling for age at first calving, study month of birth, and sire predicted
      difference for milk, there was no statistically significant association of
      calfhood morbidity with length of herd life. The estimated hazard rate ratios for
      leaving the milking herd and 95% confidence intervals for dullness, respiratory
      disease, and scours within 90 days of birth were 1.3 (0.9, 1.9), 0.9 (0.6, 1.3),
      and 1.0 (0.8, 1.3), respectively. Dullness was the only disease category with an
      estimated hazard rate ratio greater than 1, and although it was not statistically
      significant, may warrant evaluation in future studies of long term effects of
      calfhood morbidity.

PMID- 9234451
TI  - A review of the use of B. melitensis Rev 1 vaccine in adult sheep and goats.
AB  - The live Brucella melitensis Rev 1 strain is considered the best vaccine
      available for the prophylaxis of brucellosis in small ruminants. The classically
      recommended exclusive vaccination of young replacement animals has failed to
      control brucellosis in some developed countries and is frequently inapplicable in
      the developing world. Accordingly, whole-flock vaccination is the only feasible
      alternative to control B. melitensis infection in small ruminants under the
      extensive management conditions characteristic of these countries. This review
      describes the practical problems encountered and the experience acquired over the
      past decade (particularly in Spain) using the Rev 1 based control strategy. The
      vaccination of pregnant animals with full standard doses of Rev 1 administered
      subcutaneously is followed by abortion in most vaccinated animals. Reducing the
      dose of vaccine has been suggested as a method of avoiding this problem and,
      accordingly, a reduced-dose vaccination strategy has been widely used and has
      been reported as a safe and effective method of controlling small ruminant
      brucellosis. However, we reviewed field and experimental results supporting the
      fact that as a result of the induction of abortion in pregnant animals and the
      low degree of immunity conferred, reduced doses of Rev 1 should not be
      recommended as an alternative to the full standard doses. When tested in a mouse
      model, differences in residual virulence and immunogenicity have been
      demonstrated between the different Rev 1 vaccines produced world-wide. These
      differences could account for the discrepancies in safety results obtained in
      mass vaccination trials in different countries. The induction of abortions when
      vaccinating pregnant animals means that there is no entirely safe strategy for
      Rev 1 vaccination. Conjunctival vaccination is safer than subcutaneous
      vaccination but is not safe enough to be applied regardless of the pregnancy
      status of the animals, and should be used only under restricted conditions. For
      sheep, conjunctival administration of standard doses of Rev 1 during the late
      lambing season or during lactation is recommended as a whole-flock vaccination
      strategy.

PMID- 9234453
TI  - The pharmacology of amino-acid responses in septal neurons.
AB  - Septal cholinergic neurons are known to play an important role in cognitive
      processes including learning and memory through afferent innervation of the
      hippocampal formation and cerebral cortex. The septum contains not only
      cholinergic neurons but also various types of neurons including GABA (gamma
      aminobutyric acid)-ergic neurons. Although synaptic transmission in the septum is
      mediated primarily by the activation of excitatory and inhibitory amino-acid
      receptors, it is possible that a distinct phenotype of neuron is endowed with a
      different type for each of the amino-acid receptors and thus they play different
      roles from each other, since it has been demonstrated within the septum that
      there is a regional distribution of various types of amino-acid receptor
      subunits, their expression as different combinations within a specific cell may
      produce receptor channels with disparate functional properties. As a first step
      towards knowing the various functions of septal cholinergic neurons, we
      characterized the functional properties of glutamate, GABA (type A; GABAA) and
      glycine receptor channels on cultured rat septal neurons which were
      histologically identified to be cholinergic. These were similar to those of
      receptor channels on other types of neurons, except for the actions of some
      neuromodulators. The septal N-methyl-D-aspartate receptor channel was distinct in
      being less sensitive to Mg2+ and in a voltage-dependent action of Zn2+. The
      septal GABAA receptor channel exhibited a lanthanide site whose activation
      resulted in a positive allosteric interaction with a binding site of
      pentobarbital. The septal glycine receptor channel was only positively modulated
      by Zn2+; this action of Zn2+ was not accompanied by an inhibitory effect. Our
      data suggest that the amino-acid receptors on septal cholinergic neurons may play
      a distinct role compared to other types of neurons; this difference depends on
      the actions of neuromodulators and metal cations. It would be interesting to
      compare these effects recorded in tissue culture to those observed with septal
      cholinergic neurons in slice preparations.

PMID- 9234452
TI  - Non-adrenergic non-cholinergic (NANC) transmission to smooth muscle: 35 years on.
AB  - In 1963, two substances were thought to mediate all transmission between neurons,
      as well as between nerve and muscle in the peripheral nervous system, namely
      acetylcholine and noradrenaline. This paradigm primarily was due to the research
      of Dale, Loewi and von Euler in the first half of the century [Dale, 1937
      (Transmission of nervous effects by acetylcholine, Harvey Lect. 32, pp. 229
      245)]. However, in 1963, a series of experiments were carried out using recently
      introduced electrophysiological techniques, which showed unequivocally for the
      first time that the classical paradigm was not correct. Both inhibitory and
      excitatory junctions between nerves and smooth muscle cells were shown to exist
      in which transmission was mediated by non-adrenergic, non-cholinergic (NANC)
      transmitters. In the succeeding 35 years, identification of these NANC
      transmitters has been a major task of neuropharmacology, with nitric oxide,
      neuropeptides, and purines being isolated. This review presents an historical
      account of the developments this century of the classical paradigm, of how it was
      displaced, and of the progress made in identifying the neuromuscular transmitters
      of the autonomic nervous system.

PMID- 9234454
TI  - Prevention of the common mental disorders: a public health perspective.

PMID- 9234455
TI  - The National Psychiatric Morbidity surveys of Great Britain--strategy and
      methods.
AB  - BACKGROUND: This paper describes the rationale and methodology of the first
      national psychiatric morbidity surveys to be carried out in Great Britain. The
      objectives of the surveys were to estimate the prevalence of psychiatric
      morbidity among adults aged 16-64 living in Great Britain; to identify the nature
      and extent of social disabilities associated with psychiatric morbidity; to
      describe the use of health and social services by people with psychiatric
      morbidity and to investigate the association between mental illness and potential
      environmental risk factors in a household sample. METHODS: Four separate surveys
      were carried out in order to meet the objectives; a private household sample (N =
      10108), a sample of institutions caring for the mentally ill (N = 1191), a sample
      of homeless people (N = 1166), and a supplementary sample of patients with
      psychosis living in private households (N = 350). A two-stage assessment
      procedure was used, in which all subjects were given the Revised Clinical
      Interview Schedule (CIS-R) administered by lay interviewers to assess neurotic
      symptoms and disorders and a psychosis screen, including the Psychosis Screening
      Questionnaire. Those who were positive on the psychosis screen were then
      interviewed by psychiatrists using the SCAN (incorporating the tenth edition of
      the Present State Examination). CONCLUSIONS: Large scale national surveys such as
      this augment the inadequate data on psychiatric morbidity that are routinely
      available and are, therefore, an important source of information upon which to
      base policy and generate aetiological hypotheses. These surveys provide a
      possible model for similar surveys in other countries.

PMID- 9234456
TI  - The National Psychiatric Morbidity surveys of Great Britain--initial findings
      from the household survey.
AB  - BACKGROUND: This paper describes the Household Survey from the National Survey of
      Psychiatric Morbidity. This covered a sample drawn at random from the population
      of Britain, with the exception of the Highlands and Islands of Scotland. METHODS:
      The Postcode Address file was used as the sampling frame. Nearly 13000 adults
      aged 16-65 were selected for interview, of whom 10108 (79.4%) were successfully
      interviewed. Eight per cent could not be contacted and 13% refused interview.
      Psychiatric assessment was carried out by lay interviewers using the CIS-R.
      Subjects were also screened for psychosis, and screen-positive individuals were
      examined by psychiatrists using SCAN. RESULTS: Sixteen per cent of subjects
      scored above the standard cut-off of 12 on the CIS-R. The overall 1-week
      prevalence of neurotic disorder was 12.3% in males and 19.5% in females.
      Unmarried and post-marital groups had high rates of disorder, as did single
      parents and people living on their own. Respondents in Social Class I had notably
      lower rates of neurotic disorder than the remainder of the sample. Unemployment
      was strongly associated with disorder. Subjects living in urban areas had a
      higher overall prevalence, but there was no significant variation by region.
      Black respondents had higher rates of disorders that were entirely explained by
      their age, family type and social class. Individual neurotic disorders were all
      significantly commoner in women, with the exception of panic disorder. The 1-year
      prevalence of functional psychoses was 4 per 1000, with no sex difference.
      Alcohol and drug dependence was considerably more prevalent in men. CONCLUSIONS:
      For the first time, the survey provides data on the prevalence and correlates of
      psychiatric disorder on a nationwide sample that can be used to inform equitable
      and effective national psychiatric services.

PMID- 9234457
TI  - Incidence and outcome of schizophrenia in whites, African-Caribbeans and Asians
      in London.
AB  - BACKGROUND: Several previous studies have indicated high rates of schizophrenia
      in African-Caribbeans in the UK compared to White population. METHOD: All people
      aged 18 to 64 years residing in two health districts in London who made contact
      with hospital or community services over a 1-year (Whites) or 2-year (ethnic
      minorities) period were screened for psychotic symptoms. RESULTS: One hundred and
      twenty-three patients passed the screen, of whom 100 were assigned a
      schizophrenic class by the CATEGO program. Of these, 38 were White, 38 African
      Caribbean and 24 Asian. The incidence rate for broad schizophrenia was
      significantly higher for African-Caribbeans than for Whites. Asians showed a high
      rate among people age 30 and over, particularly women. Poor outcome at 1-year
      follow-up was significantly more common for African-Caribbeans than for the other
      two groups. The proportion of African-Caribbeans with a poor outcome was two and
      a half times greater than that of Whites. On a range of seven socio-demographic
      variables, African-Caribbeans differed from the other two groups only on
      unemployment. CONCLUSIONS: A multitide of factors play a role in the aetiology of
      schizophrenia. Comparison of environmental factors in these groups may identify
      factors that contribute to the aetiology of schizophrenia.

PMID- 9234458
TI  - Increased incidence of psychotic disorders in migrants from the Caribbean to the
      United Kingdom.
AB  - BACKGROUND: Several studies have replicated the finding of increased incidence of
      schizophrenia and related psychoses in first and second generation migrants from
      the Caribbean. The finding has remained consistent in studies employing different
      methods, but concern has been expressed about indirect methods of calculating the
      population at risk. This study aims to overcome these short-comings. METHOD: A
      further prospective study was undertaken in Nottingham assembling an inception
      cohort of psychotic patients (N = 168) presenting from a defined catchment area.
      The 1991 census, which includes codings for self-ascribed ethnic origin, was used
      to calculate the denominator, employing correction factors for potential under
      enumeration. Case-ascertainment was based upon all service contacts and subjects
      had in-depth assessments including the SCAN. Collateral history was obtained from
      informants. RESULTS: Subjects born in the Caribbean, or who had one or both
      parents born in the Caribbean, had a greatly elevated risk (incidence ratios
      above 7) for all psychotic disorders and for ICD-10 (DCR)-defined F20
      Schizophrenia. CONCLUSIONS: The size of the increase and the methodological
      safeguards employed support the validity of this now highly replicated finding. A
      personal or family history of migration from the Caribbean is a major risk factor
      for psychosis; the consistency of this finding justifies a systematic evaluation
      of potential aetiological factors. Any hypothesis derived from the evidence so
      far must explain: increased incidence in first and second generation migrants;
      increased risk for all psychoses (including affective psychoses); and an effect
      specifically associated with a migration history from the Caribbean to Northern
      Europe.

PMID- 9234459
TI  - Schizophrenia in Surinamese and Dutch Antillean immigrants to The Netherlands:
      evidence of an increased incidence.
AB  - BACKGROUND: Reports of an increased incidence of schizophrenia in Afro-Caribbean
      immigrants to the UK are a matter of much debate. It is of interest, therefore,
      that in the 1970s and 1980s many immigrants from Surinam and The Netherlands
      Antilles have settled in The Netherlands. The purpose of our study was to compare
      the risk of a first admission for schizophrenia for Surinamese- and Antillean
      born persons aged 15-39 years to that for their Dutch-born peers in the period
      1983-1992. METHODS: We used data from the Dutch psychiatric registry. Age
      adjusted relative risks were calculated using Poisson regression analysis.
      RESULTS: The risk for the immigrants was found to be three to four times higher
      than that for the Dutch-born. Age-adjusted relative risks were significantly
      higher for male than for female immigrants. CONCLUSIONS: The results provide
      evidence of an increased incidence in these immigrant groups and support similar
      findings on Afro-Caribbeans in the UK. Migration from Surinam was on such a large
      scale that selective migration of persons at risk for the disorder is unlikely to
      account entirely for these findings.

PMID- 9234460
TI  - Increased rates of schizophrenia among immigrants: some methodological concerns
      raised by Danish findings.
AB  - BACKGROUND: Several studies during recent years have reported an increased
      occurrence of schizophrenia in selected immigrant groups. However, difficulties
      in establishing the population denominator for immigrant rates of mental
      disorder, selective referral for treatment, and other problems may have
      influenced such results. The current study aims at testing empirically the
      influence of some of these methodological problems. METHODS: Using nationwide
      case register data from Denmark, the diagnosis specific first-admission rates
      were compared between persons born in Denmark and other countries respectively. A
      case-control design was used to compare schizophrenia risk between different
      immigrant groups. RESULTS: Incidence rates of mental disorders among non-Danish
      residents calculated from admission data showed increased rates of schizophrenia
      (RR 1.7) and non-affective functional psychoses (RR 1.9). A case-control analysis
      utilizing non-psychotic admissions as control for schizophrenic admissions
      yielded essentially the same result, thus excluding selective referral as the
      sole explanation of the increased schizophrenia rate. However, this was almost
      exclusively due to increased rates in individuals born in countries neighbouring
      on Denmark. CONCLUSIONS: While selective risk factors may be operating in various
      groups of immigrants, caution should be warranted in the interpretation of
      immigrant studies as large portions of transient visitors may obscure actual
      rates of mental disorders.

PMID- 9234461
TI  - The need for psychiatric treatment in the general population: the Camberwell
      Needs for Care Survey.
AB  - BACKGROUND: This paper presents the first results of a two-stage psychiatric
      population survey, which uses a new method of directly evaluating needs for
      specific psychiatric treatment and the extent to which they have been met.
      METHOD: The sample was drawn at random from the population of an area of inner
      south London with high levels of deprivation. Seven hundred and sixty subjects
      aged 18-65 completed the GHQ-28. All those scoring > 5 and half of the rest were
      invited to take part in the second stage, comprising measures of mental state
      (SCAN), social role performance (SRPS), life events and difficulties (LEDS) and a
      Treatment Inventory. This information was used to rate the community version of
      the Needs for Care Assessment (NFCAS-C). RESULTS: In all, 408 subjects were
      interviewed in the second stage. The weighted 1 month prevalence of
      hierarchically ordered ICD-10 psychiatric disorders was 9.8%, the 1 year
      prevalence 12.3%. The equivalent prevalences for depressive episode were 3.1% and
      5.3% respectively, while those for anxiety states were both 2.8%. At interview
      nearly 10% of the population were identified as having a need for the treatment
      of a psychiatric condition. This rose to 10.4% if the whole of the preceding year
      was assessed. Less than half of all potentially meetable needs were met. There
      was only partial overlap between diagnosis and an adjudged need for treatment.
      CONCLUSION: A majority of people with mental health problems do not have proper
      treatment; given more resources and greater public and medical awareness, most
      could be treated by family doctors.

PMID- 9234462
TI  - Diagnostic boundaries, reasoning and depressive disorder, I. Development of a
      probabilistic morbidity model for public health psychiatry.
AB  - BACKGROUND: In recent years diagnostic practice in psychiatry has become
      increasingly structured in an attempt to standardize definitions of disorders and
      improve reliability. At the same time there has been an increasing recognition of
      the need to take account of uncertainty in the process of diagnostic decision
      making. For the most part, diagnosis is still represented by a binary outcome
      while this is known to entail a substantial loss of information. Many diagnostic
      schemes involve, in part, taking thresholds on the numbers of symptoms required
      from symptom lists. METHODS: A model is proposed here, using ideas derived from
      latent class analysis to permit generalization from these schemes through moving
      from a binary to a probabilistic measure of psychiatric case status and replacing
      thresholds with smoothed transitions. RESULTS: An outcome measure is produced
      where disorder status is expressed in terms of probabilities without changing the
      meaning of the original measure. Prevalence estimates (using ICD-10 Depressive
      Episode criteria) are more stable and can be given with increased precision.
      CONCLUSIONS: Disorder status when expressed in this way retains more diagnostic
      information and provides a useful extension to traditional binary analyses when
      looking at prevalence and risk factor estimation.

PMID- 9234463
TI  - Diagnostic boundaries, reasoning and depressive disorder, II. Application of a
      probabilistic model to the OPCS general population survey of psychiatric
      morbidity in Great Britain.
AB  - BACKGROUND: Reliable prevalence and risk estimation of psychiatric disorder is a
      cornerstone to achieving objectives in public health psychiatry. Research
      strategies have increasingly depended, therefore, upon the progressive evolution
      and refinement of diagnostic approaches designed to reflect better current
      knowledge concerning prognosis, course and outcome but essentially the need to
      improve agreement between users of the various schemes. METHODS: This paper
      contrasts a conventional with a probabilistic approach to the diagnosis of
      depression based upon the OPCS United Kingdom National survey of psychiatric
      morbidity. The probabilistic approach, while designed to mimic current diagnostic
      practice in relation to the depressive disorders, naturally includes provision
      for the allocation of respondents on a scale of diagnostic uncertainty according
      to the severity of their presenting condition. RESULTS: Findings are reported
      arising from the application of the probabilistic method to three areas of
      research interest in public health psychiatry, namely; an evaluation of
      additivity of event exposure and depressive morbidity, secondly use of the
      approach for investigating psychosocial models of depressive disorder and thirdly
      for assessing the agreement between depressive disorder when classified according
      to competing diagnostic schemes. CONCLUSIONS: The results show application of the
      probabilistic approach to provide a firm basis for achieving gains in both the
      stability and precision of risk profile estimation for depressive conditions.

PMID- 9234464
TI  - The impact of psychiatric disorders on work loss days.
AB  - BACKGROUND: To examine relationships between recent DSM-III-R psychiatric
      disorders and work impairment in major occupational groups in the US labour
      force. METHOD: Data are from the US National Comorbidity Survey (NCS), a survey
      of respondents ages 15-54 in the US. Employed people are the focus of the report.
      RESULTS: There is substantial variation across occupations in the 30-day
      prevalences of NCS/ DSM-III-R psychiatric disorders, with an average prevalence
      of 18.2% (range: 11.0-29.6%) for any disorder. The average prevalences of
      psychiatric work loss days (6 days per month per 100 workers) and work cutback
      days (31 days per month per 100 workers), in comparison, do not differ
      significantly across occupations. Work impairment is more strongly concentrated
      among the 3.7% of the workforce with co-morbid psychiatric disorders (49 work
      loss days and 346 work cutback days per month per 100 workers) than the 14.5%
      with pure disorders (11 work loss days and 66 work cutback days per month per 100
      workers) or the 81.8% with no disorder (2 work loss days and 11 work cutback days
      per month per 100 workers). The effects of psychiatric disorders on work loss are
      similar across all occupations, while effects on work cutback are greater among
      professional workers than those in other occupations. CONCLUSION: The results
      reported here suggest that work impairment is one of the adverse consequences of
      psychiatric disorders. The current policy debate concerning insurance coverage
      for mental disorders needs to take these consequences into consideration.

PMID- 9234465
TI  - Fifteen years on: evolving ideas in researching sex differences in depression.
AB  - BACKGROUND: A cohort study of a socially homogeneous group of teachers was
      commenced in 1978 to pursue possible risk factors contributing to the recognized
      female preponderance of depression. METHODS: Multiple measures of depressive
      experience included: (i) lifetime rates, duration and number of depressive
      episodes using two caseness definitions, DSM-III-R major depression and 'all
      depression' (which included a category of minor depression); (ii) self-report
      measures of state and trait depression, neuroticism, and self-esteem. DSM-III-R
      anxiety disorder rates are also reported and co-morbidity with major depression
      examined. RESULTS: At the 15-year review in 1993, the sample had a mean age of 39
      years, there was a trend for a female preponderance in lifetime rates of major
      depression and 'all depression' (and which was more pronounced with the inclusion
      of data for anxiety disorders), with statistically significant differences in
      rates of social and simple phobias and combined anxiety disorders. Mean
      neuroticism scores were consistently higher for women. CONCLUSIONS: The strong
      association between anxiety and depressive disorders suggests that greater
      reporting of anxiety and higher neuroticism scores in women may be a key
      determinant that contributes to any female preponderance in depression rates.

PMID- 9234466
TI  - What voices can do with words: pragmatics of verbal hallucinations.
AB  - BACKGROUND: In this paper we consider verbal hallucinations as inner speech with
      pragmatics. The specific pragmatic properties of verbal hallucinations
      investigated included the number of voices, the characteristics that individuate
      the voices, the sequential characteristics of the dialogues between voice hearers
      and their voices, the dialogical positioning of voices hearers, voices and other
      individuals, and how the voices influence voice hearers' activities. METHODS:
      These properties were examined in structured interviews with 28 individuals, 14
      of whom had a diagnosis of schizophrenia, while 14 were students who did not use
      psychiatric services. RESULTS: The analysis showed that voices were most
      frequently individuated with reference to individuals significant to voice
      hearers. The talk with voices was typically mundane and related to voice hearers'
      on-going activities, as is the case for ordinary inner speech. The voices were
      typically orientated towards the voice hearer, without direct access to each
      other or to other people. Contrary to received wisdom, the voices typically did
      not impel actions of voice hearers, rather they influenced voice hearers'
      decisions on how to act. This was so irrespective of the diagnostic status of
      informants. Finally, we have found some differences between the voices of
      informants with, and without, schizophrenia. These concerned the alignment of
      voices, the type of action required by a voice and the degree of dialogical
      engagement between voices and voice hearers. CONCLUSIONS: We conclude that verbal
      hallucinations can be fruitfully considered to be a genus of inner speech.
      Pragmatics can be used as a framework to distinguish verbal hallucinations in
      different populations.

PMID- 9234467
TI  - Voices of the mad: patients' letters from the Royal Edinburgh Asylum, 1873-1908.
AB  - BACKGROUND: This paper is based on a rich archive of 1151 letters by patients,
      who were admitted to the Royal Edinburgh Asylum during the reign of Thomas
      Clouston (1873-1908). METHODS: All letters were examined for evidence of
      psychopathology, and the material obtained was organized under the various
      psychopathological categories, such as delusions or hallucinations, as defined by
      Sims (1988). RESULTS: A descriptive account of patient symptomatology is given.
      It is found that nineteenth century psychopathology is very similar to that of
      the modern day, and that most forms of morbid mental phenomena can be found in
      the patients' letters. More specifically, most of the cardinal symptoms of
      schizophrenia were described in the patients' correspondence. The letters also
      illustrate how mental symptoms reflect the cultural and scientific concerns of
      their time. CONCLUSIONS: The evidence in the patients' letters argues for the
      unchanging nature of mental illness across time, at least for the last 120 years.
      It also demonstrates that patients admitted to the Royal Edinburgh Asylum
      suffered from serious mental illness, and it undermines the view that the Asylum
      was simply a dumping ground for society's disaffected.

PMID- 9234468
TI  - Patterns of behaviour problems among pre-school children.
AB  - BACKGROUND: Previous research has suggested that behavioural problems displayed
      during the pre-school years are best understood as undifferentiated difficulties
      in manageability. The present study explored this issue, by examining the
      structure of British parents' ratings of their pre-school children's behavioural
      problems. METHOD: The 19-item Behavioural Checklist (BCL; Richman, 1977) was
      completed by 1047 parents of 3-year-old children taking part in an
      epidemiological survey of child development. RESULTS: Factor analysis revealed
      six factors representing poor social adjustment, poor emotional adjustment, sleep
      problems, over-activity/inattention, eating problems and soiling. When these
      scores were used as a basis for cluster analysis, problem types clustered around
      six centres. The first, and largest, grouping was of children with no problems.
      Three further large groupings displayed specific but moderate problems (over
      active, timid, and naughty children). The final two groupings displayed more
      extreme problems including anti-social behaviour. In one group these were
      accompanied by severe emotional problems and in the other by signs of
      hyperactivity. The reliability and validity of these clusters was supported.
      Parental ratings of behaviour problems taken when the children were 8-years-old
      suggested that the children in the hyperactive/conduct group were likely to have
      continued difficulties. CONCLUSION: This paper argues against the homogeneity of
      pre-school behaviour problems but supports the idea that problems of a clinically
      significant level are likely to be co-morbid, with either problems of emotional
      regulation (neurotic) or those of behavioural regulation (hyperactive)
      accompanied by problems of conduct.

PMID- 9234469
TI  - A prospective study of cognitive function in the elderly.
AB  - BACKGROUND: We report on the change in cognitive function in a population sample
      of elderly people who have been examined on two occasions more than 3 years
      apart. METHODS: A sample of 1135 persons aged 70-102 years was interviewed at
      base-line then re-interviewed 3.6 years later with the Canberra Interview for the
      Elderly, which included tests of episodic memory and cognitive speed as well as
      the Mini-Mental State Examination and the National Adult Reading Test (NART).
      RESULTS: Mortality and loss to follow-up reduced the sample to 736, of whom 614
      completed at least one test of cognitive performance on both occasions. Cognitive
      performance decreased with age, except on the NART. Decline over the follow-up
      period increased as a function of age in all cognitive measures, except the NART.
      Change in cognitive scores was close to normal distribution. Incident dementia
      was associated strongly with age and current level of cognitive performance, but
      not with rate of decline. Cognitive decline and the risk of incident dementia did
      not differ by gender. CONCLUSIONS: A score indicating possible impairment in the
      very elderly carries a worse prognosis than for the younger elderly. Decline is
      almost universal in at least one cognitive area among those over the age of 85.

PMID- 9234470
TI  - Prefrontal dysfunction in depressed patients performing a complex planning task:
      a study using positron emission tomography.
AB  - INTRODUCTION: Patients with unipolar depression show impaired performance on the
      Tower of London planning task. Positron emission tomography, which has previously
      identified resting state blood flow abnormalities in depression, was used to
      investigate neural activity associated with performance of this task in depressed
      patients and normal controls. METHODS: Six patients with unipolar depression and
      six matched controls were scanned while performing easy and hard Tower of London
      problems in a one-touch computerized paradigm and while performing a
      perceptuomotor control task. RESULTS: The patients in this study showed an
      expected task-related performance deficit compared with normal subjects. In
      normal subjects, the task engaged a network of prefrontal cortex, anterior
      cingulate, posterior cortical areas and subcortical structures including the
      striatum, thalamus and cerebellum. Depressed patients failed to show significant
      activation in the cingulate and striatum; activation in the other prefrontal and
      posterior cortical regions was significantly attenuated relative to controls.
      Crucially, patients also failed to show the normal augmentation of activation in
      the caudate nucleus, anterior cingulate and right prefrontal cortex associated
      with increasing task difficulty. CONCLUSIONS: These findings provide evidence for
      cingulate, prefrontal and striatal dysfunction associated with impaired task
      performance in depression. The present results are consistent with a central role
      of cingulate dysfunction in depression as well as suggesting impaired
      frontostriatal function.

PMID- 9234471
TI  - Depressive disorders among older residents in a Chinese rural community.
AB  - BACKGROUND: Two recent surveys of depression among Chinese elderly people sampled
      different populations, used different case ascertainment methods and resulted in
      a seven-fold difference in prevalence rates. The present study was conducted to
      compare prevalence rates obtained with two commonly used methods in the same
      population, and to examine the risk factors for depression. METHODS: The target
      population included all residents aged 65 years and over in a rural Chinese
      community. Participants were interviewed for demographic and medical information,
      examined by a neurologist and administered Chinese versions of the Geriatric
      Depression Scale-Short Form (GDS-S), the Cognitive Abilities Screening Instrument
      (CASI) and an Activities of Daily Living (ADL) form. Individuals who screened
      positive on the GDS-S were also interviewed by a psychiatrist for diagnosis
      according to the DSM-III-R criteria. RESULTS: Among the 1313 participants, 26%
      screened positive on the GDS-S and 13% were diagnosed as having a depressive
      disorder, including 6.1% with major depression. Individuals with depressive
      disorders were more likely to have poor ADL scores, lower CASI scores, and
      chronic physical illnesses. They were also more likely to be female, older,
      illiterate and without a spouse, but adding these variables did not increase the
      overall association with the GDS-S score. CONCLUSIONS: Depression was quite
      common in this Chinese rural geriatric population. The prevalence rate was twice
      as high when judged by depression symptomatology rather than clinical diagnosis.
      The critical risk factors were functional impairments, poor cognitive abilities
      and the presence of chronic physical illnesses.

PMID- 9234472
TI  - Hippocampal volume in women victimized by childhood sexual abuse.
AB  - BACKGROUND: Several prior studies have found reduced hippocampal volume in
      victims of psychological trauma with post-traumatic stress disorder (PTSD). We
      were interested to determine if this finding was evident in women who were
      victimized by severe sexual abuse in childhood. METHODS: In this study,
      hippocampal volume was measured using quantitative magnetic resonance imaging
      (MRI) in 21 women who reported being severely sexually abused in childhood and 21
      socio-demographically similar women without abuse histories. RESULTS: Women who
      reported sexual victimization in childhood had significantly reduced (5% smaller)
      left-sided hippocampal volume compared to the non-victimized women. Hippocampal
      volume was also smaller on the right side, but this failed to reach statistical
      significance. Left-sided hippocampal volume correlated highly (rs = -0.73) with
      dissociative symptom severity, but not with indices of explicit memory
      functioning. CONCLUSIONS: These findings, which are generally consistent with
      prior reports of reduced hippocampal volume in combat veterans with PTSD, suggest
      that diminished hippocampal size may be either a consequence of trauma exposure
      or a risk factor for the development of psychiatric complications following
      trauma exposure. The observed relationship between symptom severity and
      hippocampal volume suggests that mesial temporal lobe dysfunction may directly
      mediate certain aspects of PTSD and dissociative disorder symptomatology.

PMID- 9234473
TI  - Predicting length of stay in psychiatry.
AB  - BACKGROUND: Diagnostic Related Groups (DRGs) and Healthcare Resource Groups
      (HRGs) do not predict accurately length of stay or resources needed for treatment
      in psychiatry. This preliminary study assessed the relative contribution of
      severity of illness, in combination with other variables, in predicting length of
      stay. METHOD: Data were analysed on 115 consecutive admissions to a district
      psychiatric in-patient unit to assess the variables which most accurately predict
      length of stay. The variables included demographic data, diagnosis, clinical,
      social and behavioural measures. RESULTS: For initial admission, diagnosis of
      neurosis predicted shortest stay, but diagnosis alone accounted for only 14.6% of
      the variation in length of stay. Addition of Social Behaviour Scale score, living
      alone and specific psychiatric symptoms significantly increased the predictive
      value (adjusted R2 = 36.6%). Addition of variables available at discharge (use of
      ECT, major tranquillizers and antidepressants) significantly increased the
      adjusted R2 to 49.0%. Prediction of total length of hospitalization over a 12
      month period, from the date of initial admission, indicated that mania predicted
      the longest stay and addition of other variables meant that only 18.9% of length
      of stay was predicted. CONCLUSION: If these results are borne out in a large
      study, they indicate that diagnostic or health related groups (DRGs) are only
      likely to be useful in psychiatry if they include more detailed social, clinical
      and behavioural variables.

PMID- 9234474
TI  - Performance on the delayed word recall test (DWR) fails to differentiate clearly
      between depression and Alzheimer's disease in the elderly.
AB  - BACKGROUND: The differential diagnosis of early dementia of the Alzheimer's type
      from depression in the elderly is often made difficult by the presence of
      significant memory impairment in depressed patients. The Delayed Word Recall test
      (DWR) was developed to facilitate the early diagnosis of Alzheimer's disease. The
      DWR involves: (a) repeated elaborate encoding of ten separate words; (b) a filled
      delay; (c) delayed free recall. A recognition memory test has also been recently
      developed. The available evidence suggests impressive sensitivity and specificity
      when the DWR has been used to separate patients with early Alzheimer's disease
      from very well matched controls. METHODS: In the present study, the DWR was
      evaluated with regard to its ability to separate a group of 50 patients with
      early Alzheimer's disease from 50 elderly patients with major depression in a
      between-subjects experimental design. RESULTS: For both free recall and
      recognition indices, the between-group overlap was large. Using recommended cut
      off scores for the detection of Alzheimer's disease, 44% of the depressed
      patients would have been misclassified as demented based on their free recall
      scores, and 48% of the depressed patients would have been misclassified on the
      basis of their recognition scores. CONCLUSION: We conclude that the DWR is not
      specific enough to clearly distinguish patients with early Alzheimer's disease
      from elderly patients with major depression.

PMID- 9234475
TI  - Parasuicide, depression and the anticipation of positive and negative future
      experiences.
AB  - BACKGROUND: Previous research has shown that parasuicides' view of the future is
      characterized by an absence of anticipation of positive experiences rather than
      the presence of anticipation of negative experiences. The present study aimed to
      replicate this finding and examine whether it would also be found in parasuicides
      who were not depressed. METHOD: Depressed parasuicides (N = 27), non-depressed
      parasuicides (N = 17) and matched controls (N = 34) were assessed on their
      anticipation of future positive and negative experiences using an adapted fluency
      paradigm, where they were given a set time to generate future positive and
      negative anticipated experiences. RESULTS: Consistent with previous findings,
      parasuicides showed an overall reduced anticipation of positive experiences and
      no overall increased anticipation of negative experiences. However, the
      parasuicides did show evidence of increased negative anticipation for the
      immediate future. The results for depressed and non-depressed parasuicides were
      essentially the same. CONCLUSION: Lack of positive anticipation in the absence of
      increased negative anticipation is a feature of parasuicide. Although this lack
      of positive anticipation can occur in depression, it appears to be an independent
      feature of parasuicide.

PMID- 9234476
TI  - The killer cell inhibitory receptor genomic region on human chromosome 19q13.4.
AB  - Multiple genes encoding type I transmembrane molecules and belonging to the
      immunoglobulin superfamily have recently been localized to human chromosome
      19q13.4. These include a family of genes encoding killer cell inhibitory
      receptors (KIR) expressed on natural killer (NK) cells and subsets of T
      lymphocytes, immunoglobulin-like transcripts (ILT-1, -2 and 3) expressed on
      myeloid cells and subsets of lymphoid cells, the gp49 family of receptors
      expressed on mast cells and NK cells and the gene encoding human myeloid
      immunoglobulin A Fc receptor (CD89). The receptors have one to four extracellular
      immunoglobulin domains, and the ligands are known for some of these molecules.
      This includes the Fc alpha R and KIRs of the p58/p50 and p70/p70 delta, but the
      ligands for many others are unknown. Except for CD89, each subfamily of receptors
      exist, in two forms, of which one has a long cytoplasmic domain containing one to
      four immunoreceptor tyrosine-based inhibitory motifs (ITIM) and another form with
      a short cytoplasmic tail without ITIMs. ITIM-containing receptors can recruit
      cytoplasmic tyrosine phosphatases and provide inhibitory signals for cell
      activation, whereas receptors with a "short" tail induce activating signals. The
      19q13.4 chromosomal region is therefore now emerging as the immunoglobulin
      superfamily linkage group of genes differentially expressed on hematopoietic cell
      lineages and encoding pairs of receptors with opposing effects on signal
      transduction pathways and effector functions in hematopoietic cells.

PMID- 9234477
TI  - Genomic organization and allelic polymorphism of the human killer cell inhibitory
      receptor gene KIR103.
AB  - Killer cell inhibitory receptors (KIR) belong to the immunoglobulin superfamily
      of molecules and are expressed on natural killer (NK) cells. The KIRs of the
      p58/p50 family have two immunoglobulin domains and are ligands for HLA-Cw
      antigens, whereas the p70/p70 delta family has three immunoglobulin domains and
      comprises ligands for HLA-B antigens and possibly some HLA-A antigens. Members of
      a third KIR family, KIR103, have two immunoglobulin domains but have highest
      nucleotide sequence homology to the p70 family. The ligands for KIR103 on target
      cells are currently unknown. We here report the complete genomic organization of
      KIR103. It spans about 12 kb of DNA and consists of eight exons of which exon 1
      and exon 2 encode the leader sequence. Exon 3 encodes the first immunoglobulin
      domain (gamma 1), and exon 4 encodes the main part of the second immunoglobulin
      domain (gamma 3), which also contains sequences contributed by exon 5 and exon 6.
      Exon 6 encodes the transmembrane domain, whereas exons 7 and 8 encode most of the
      cytoplasmic domain. KIR103 is polymorphic, and two alleles, 103AS and 103LP, are
      defined in this study. Additional full-length cDNA clones for KIR103 have been
      isolated and are shown to be formed by alternative mRNA splicing with exon
      skipping. Some of these truncated KIR103 cDNA could encode shorter transmembrane
      molecules, whereas others lack the transmembrane domain and are candidate genes
      for secreted KIR products. KIR103 is localized to the KIR genetic region on
      chromosome 19q13.4.

PMID- 9234478
TI  - Genomic organization of a human killer cell inhibitory receptor gene.
AB  - We have cloned a region of human chromosome 19q13.4 which contains multiple
      killer cell inhibitory receptor (KIR) loci. By random and directed sequence
      analysis of these KIR-specific clones, we deduced the genomic structure of KIR
      genes. A locus encoding a member of the NKAT-2 family of KIRs is presented here.
      The structure of the gene is reminiscent of loci of the Fc receptor gene family,
      and the two sets of genes may derive from a common ancestor. The KIR gene
      contains potentially nine exons. The first two exons encode the leader sequence,
      as in Fc receptor genes. The third exon encodes an untranslated pseudo exon
      specifying an immunoglobulin domain with an in-frame stop codon. Expressed cDNAs
      do not contain this exon. This finding is consistent with the hypothesis that
      certain KIR genes may have been derived from the duplication of a primordial
      three immunoglobulin domain structure with subsequent skipping of one exon to
      derive genes with two expressed immunoglobulin domains. Variation in numbers of
      immunoglobulin domains in different KIR genes is facilitated by conservation of
      splicing frame in respect to the codon triplet for each immunoglobulin domain.

PMID- 9234479
TI  - HLA-B27 (B*2701) specificity for peptides lacking Arg2 is determined by
      polymorphism outside the B pocket.
AB  - B*2701 differs from B*2705-by three amino acid changes: D-->Y74, D-->N77, L-
      >A81, and from B*2702 only by two: D-->Y74 and T-->I80. Tyr74 is located in the
      C/F cavity of the peptide-binding site, and is unique to B*2701 among HLA-B27
      subtypes. Binding of natural B*2705 and B*2702 ligands to B*2701, and to mutants
      mimicking subtype changes, was analyzed. In addition, sequencing of the peptides
      bound in vivo by B*2701 and the Y74 mutant was carried out. The main distinctive
      feature of B*2701 was its presentation of peptides with Gln2. Synthetic analogs
      bound in vitro similarly as the corresponding ligands with Arg2. Moreover, both
      Gln2 and Arg2 were dominant upon pool sequencing of B*2701-bound peptides, and 2
      of 8 natural ligands contained Gln2. Suitability of Gln2 was largely determined
      by the Y74 change, as indicated by: 1) binding of Gln2 analogs to this mutant,
      and 2) detection of Gln2 by pool sequencing of Y74-bound peptides. B*2701 bound
      peptides with C-terminal aromatic or Leu residues, and interacted with these
      motifs more strongly than B*2702. The Y74 mutation alone was not responsible for
      poor binding of peptides with C-terminal basic residues to B*2701, since they
      bound efficiently and at least one was presented in vivo by this mutant. Most
      peptides bound to the A81 mutant worse than to B*2705, but frequently better than
      to B*2701 or B*2702, suggesting that other subtype changes were compensatory. The
      peptide specificity of B*2701 suggests that this subtype may determine
      susceptibility to spondyloarthropathy.

PMID- 9234480
TI  - Characterization of the porcine homologue to human platelet glycoprotein IIb-IIIa
      (CD41/CD61) by a monoclonal antibody.
AB  - Human gpIIb-IIIa or CD41/CD61 is a Ca(2+)-complex dependent heterodimer, abundant
      on platelets, that plays a key role in hemostasis. This report describes a murine
      monoclonal antibody, JM2E5, able to recognize and immunoprecipitate the
      gpIIb/IIIa surface glycoprotein from porcine platelets. Immunoprecipitation
      analysis showed an antigen molecular weight of 115 and 85 kDa under nonreducing
      conditions, and of 110, 100 and 25 kDa under reducing conditions.
      Immunohistochemistry analyses of frozen sections from several porcine lymphoid
      organs gave specific staining on platelets. EDTA treated platelets were studied
      by flow cytometry indicating that the epitope recognized was Ca(2+)-complex
      independent. Western-blotting experiments with porcine platelet extracts gave an
      antigen molecular weight of 85 kDa under nonreducing conditions, thus localizing
      the epitope recognized by JM2E5 on the complex light chain gpIIIa or CD61. JM2E5
      was also cross-reacting with human, bovine and horse platelets, as shown by flow
      cytometry. This mAb would allow further studies on this important adhesion
      molecule on horses, ruminants and pigs, and it should be especially useful as a
      general anti-porcine platelet reagent.

PMID- 9234481
TI  - Population studies of the human V kappa A18 gene polymorphism in Caucasians,
      blacks and Eskimos. New functional alleles and evidence for evolutionary
      selection of a more restricted antibody repertoire.
AB  - Immunoglobulin gene polymorphisms are interesting because they reflect
      differences in the available antibody repertoire which may affect the
      susceptibility to specific infections. Until recently, the human V kappa gene,
      A18, was known as a nonfunctional gene only. In this study, we cloned and
      sequenced four apparently functional alleles and determined the gene frequencies
      in three well-defined populations: Danish Caucasians, eastern Greenland Eskimos
      and Mozambican blacks. The A18b allele that was recently described in Native
      American Navajos by Atkinson et al. was found in all three populations with gene
      frequencies of 8%, 45% and 23% in Caucasians, Eskimos and blacks, respectively.
      Conversely, the frequencies of the nonfunctional A18a allele were 92%, 55% and
      57%. Further, three new A18 alleles, c, d, and e were found exclusively in
      blacks, among whom they had an total frequency of 19%. These data indicate that
      both the A18a and A18b alleles originated before the diversification of Africans
      and non-Africans 90,000 years ago, whereas the A18c, A18d and A18e alleles may
      have a more recent origin. The functionality of the A18b allele was documented by
      the demonstration of properly rearranged and somatically hypermutated A18b
      messenger RNA present in the blood lymphocytes of individuals carrying this
      allele. The expression clearly exceeded that of a known functional V gene, A2,
      indicating that functional A18 alleles contribute significantly to the available
      antibody repertoire. In this context, it is surprising that the functional A18b
      allele apparently has been negatively selected in the Caucasian population, among
      whom 85% completely lack a functional gene.

PMID- 9234482
TI  - Possible association between HLA antigens and the response to interferon in
      Japanese patients with chronic hepatitis C.
AB  - Correlation between the major histocompatibility complex class I antigens (HLA-A,
      -B and -C) and the elimination from serum of hepatitis C virus in patients with
      chronic hepatitis C has not been understood. We analyzed HLA phenotypes and their
      relationship to the efficacy of interferon treatment. Of the 172 patients who
      were treated with 9 million units of interferon-alpha 2a three times a week for 6
      months, 54 patients were responders and 118 patients were non-responders. No
      significant difference was observed between the 172 patients and 199 healthy
      subjects with regard to the frequencies of HLA-A, -B and -C antigen phenotypes.
      However, HLA-B55, B62, CW3 and CW4 frequencies were significantly higher in
      responders than in non-responders to the interferon treatment. CW4 was found to
      link with B62, but other phenotypes were independent each other. Patients with
      HLA B55, B62 and CW3 had a significantly lower viral load, and showed a better
      response to interferon. These results suggest that HLA system does not have an
      influence on the evolution towards chronicity of the disease due to hepatitis C
      virus, but HLA B55, B62 or CW4, and CW3 may be a virus quantity-regulating
      factors which then affect to response to the interferon treatment, indicating
      that these HLA antigens in conjunction with a viral peptide is a key target
      antigen for cytotoxic T lymphocytes in patients with chronic hepatitis C.

PMID- 9234483
TI  - Molecular characterization of HLA-C incompatibilities in HLA-ABDR-matched
      unrelated bone marrow donor-recipient pairs. Sequence of two new Cw alleles
      (Cw*02023 and Cw*0707) and recognition by cytotoxic T lymphocytes.
AB  - While the influence of HLA-AB and -DRB1 matching on the outcome of bone marrow
      transplantation (BMT) with unrelated donors is clear, the evaluation of HLA-C has
      been hampered by its poor serological definition. Because the low resolution of
      standard HLA-C typing could explain the significant number of positive cytotoxic
      T lymphocyte precursor frequency (CTLpf) tests found among HLA-AB-subtype,
      DRB1/B3/B5-subtype matched patient/donor pairs, we have identified by sequencing
      the incompatibilities recognized by CD8+ CTL clones obtained from such positive
      CTLpf tests. In most cases the target molecules were HLA-C antigens that had
      escaped detection by serology (e.g. Cw*1601, 1502 or 0702). Direct recognition of
      HLA-C by a CTL clone was demonstrated by lysis of the HLA class I-negative
      721.221 cell line transfected with Cw*1601 cDNA. Because of the functional
      importance of Cw polymorphism, a PCR-SSO oligotyping procedure was set up
      allowing the resolution of 29 Cw alleles. Oligotyping of a panel of 382
      individuals (including 101 patients and their 272 potential unrelated donors, 5
      related donors and 4 platelet donors) allowed to determine HLA-C and HLA A-B-Cw
      DRB1 allelic frequencies, as well as a number of A-Cw, B-Cw, and DRB1-Cw
      associations. Two new HLA-Cw alleles (Cw*02023 and Cw*0707) were identified by
      DNA sequencing of PCR-amplified exon 2-intron 2-exon 3 amplicons. Furthermore, we
      determined the degree of HLA-C compatibility in 287 matched pairs that could be
      formed from 73 patients and their 184 potential unrelated donors compatible for
      HLA-AB by serology and for HLA-DRB1/ B3/B5 by oligotyping. Cw mismatches were
      identified in 42.1% of these pairs, and AB-subtype oligotyping showed that 30% of
      these Cw-incompatible pairs were also mismatched for A or B-locus subtype. The
      degree of HLA-C incompatibility was strongly influenced by the linkage with B
      alleles and by the ABDR haplotypes. Cw alleles linked with B*4403, B*5101, B18,
      and B62 haplotypes were frequently mismatched. Apparently high resolution DNA
      typing for HLA-AB does not result in full matching at locus C. Since HLA-C
      polymorphism is recognized by alloreactive CTLs, such incompatibilities might be
      as relevant as AB-subtype mismatches in clinical transplantation.

PMID- 9234484
TI  - HLA class II DRB1, DQA1 and DQB1 polymorphisms in the Polish population from
      Wielkopolska.
AB  - HLA DRB1, DQA1 and DQB1 alleles were determined by DNA PCR-SSO typing in a sample
      of 99 individuals originating from Wielkopolska (midwestern Poland). A high
      number of alleles (38 DRB1, 8 DQA1 and 14 DQB1) was detected at each locus, many
      of them presenting notable frequencies in this population. The three HLA loci are
      thus characterized by very high heterozygosity levels (93% for DRB1, 85% for
      DQA1, and 88% for DQB1), which confirms the results found for other European
      populations. A total of 6 DRB1-DQA1-DQB1 haplotypes are detected with an
      estimated frequency higher than 5%, namely, DRB1*1501-DQA1*0102-DQB1*0602,
      DRB1*0701-DQA1*0201-DQB1*0201, DRB1*0101-DQA1*0101-DQB1*0501, DRB1*1101-DQA1*0501
      DQB1*0301, DRB1*03011-DQA1*0501-DQB1*0201, and DRB1*1301-DQA1*0103-DQB1*0603. A
      genetic distance analysis between the Polish and other world populations tested
      for HLA class II indicates that the Wielkopolska community is close to
      geographically close, rather than linguistically related populations from Europe.
      More generally, a good agreement between genetics and geography is found for DRB1
      and DQB1 polymorphisms in Europe, suggesting that these two loci are highly
      informative for assessing historical relationships among humans.

PMID- 9234485
TI  - Genetic markers in the Tuvan population of Todja, Siberia.
AB  - Todja is a secluded region of northern Tuva-situated in the Sayany Mountains,
      Siberia. The aboriginal population of Todja is Tuvan. A total of 128 healthy
      Tuvans living in Todja were typed for HLA-A, -B and -C antigens and several
      plasma and erythrocyte protein polymorphisms (Hp, Tf, Gc, ESD, ACP, PGM1, PGD and
      ADA). The observed frequencies of all 8 blood protein and HLA genotypes were in
      agreement with Hardy-Weinberg expectations. The most frequent HLA antigens in
      Todjans are A2 (0.36), A3 (0.24), A9 (0.50), B15 (0.34) and B40 (0.50). HLA
      haplotypes A2B5, A2B40, A9B15 and A9B40 are most common in this population. The
      observed frequencies of protein polymorphisms and HLA antigens and haplotypes in
      Todjans are similar to those of other Mongoloid populations. A comparison of HLA
      frequencies currently observed in Todjans with those obtained 20 years ago at the
      same locality showed minor changes attributable to the effect of migration.

PMID- 9234486
TI  - Association between polymorphisms at the human IL-10 locus and systemic lupus
      erythematosus.
AB  - Recent studies have shown elevated IL-10 levels in several rheumatic autoimmune
      diseases, and particularly in systemic lupus erythematosus (SLE). Such changes
      may have a genetic basis. We studied two novel polymorphic dinucleotide repeats
      in the IL-10 promoter region (IL10.G and IL10.R) in order to investigate their
      possible significance in association with this condition in a group of 56
      Caucasian SLE patients compared with 102 ethnically matched controls. The results
      show that there is an allelic imbalance between SLE patients and controls at the
      IL10.G microsatellite; this observation is supported by a significant difference
      in genotype distribution. The nature of autoantibody production and the presence
      or absence of renal involvement also appeared to be associated with certain
      IL10.G microsatellite alleles, although the small size of individual clinical sub
      groupings may have influenced this result. No association with the IL10.R
      microsatellite was observed. Overall, the differences observed at the IL10.G
      microsatellite between SLE patients and controls suggest that the IL-10 locus
      contributes to the genetic background important for the development of this
      disease. Although the moderate sample size described in this study requires that
      the results be interpreted carefully, they provide an interesting and useful
      framework for future study.

PMID- 9234487
TI  - Expression of human leukocyte antigens class I and class II on cultured biliary
      epithelial cells after cytomegalovirus infection.
AB  - The influence of cytomegalovirus (CMV) infection on the HLA expression on
      cultured biliary epithelial cells (BEC) was investigated. CMV-infection augmented
      expression of HLA class I but not of HLA class II. CMV reduced the IFN-gamma
      mediated induction of the de novo expression of HLA class II while the stimulated
      expression of HLA class I was not impaired. Autologous but not allogeneic PBL
      responded to CMV-infected BEC. This response resulted in upregulation of HLA
      class I on BEC which was significantly higher compared with the expression on
      infected BEC alone or on uninfected BEC cocultured with autologous PBL. The
      results suggest that CMV modulates the immunogenic potential of BEC, which is
      important for the HLA and CMV-mediated pathomechanisms in vivo.

PMID- 9234488
TI  - The novel HLA-Cw*1802 allele is associated with B*5703 in the Bubi population
      from Equatorial Guinea.
AB  - The HLA-Cw*1801 specificity, a Cw7/Cw4 hybrid allele, has recently been described
      in association with B*8101 (formerly B"DT"). In this study, the new Cw*1802
      variant, differing from Cw*1801 at exon 5, is found associated with B*5703 in
      Bubi individuals from Equatorial Guinea. Confirmatory complete coding regions of
      B*5703 and B*3910 are also reported.

PMID- 9234489
TI  - A novel HLA-B27 allele (B*2711) encoding an antigen reacting with both B27- and
      B40-specific antisera.

PMID- 9234490
TI  - Identification of a new HLA-B allele, HLA-B*0708.

PMID- 9234491
TI  - A Bw6-associated B44 allele (B*4409) identified by SSOP and corresponding
      serological results.

PMID- 9234492
TI  - Description of two new HLA-DRB alleles (DRB1*0310 and DRB3*01012) found in a
      Spanish infant.

PMID- 9234493
TI  - Identification of a new DRB4 allele (DRB4*0105) by sequence-based typing.

PMID- 9234494
TI  - Identification and nucleotide sequence of two novel DRB3 alleles, DRB3*0102 and
      DRB3*010133.

PMID- 9234495
TI  - A novel DPA1 allele (DPA1*0203) composed of known epitopes.

PMID- 9234496
TI  - Correction of the DPB*02011 allele and assignment of DRB3*0202 to the cell line
      WT49.

PMID- 9234497
TI  - Correction of the HLA-G*01012 genomic sequence.

PMID- 9234498
TI  - Nomenclature for factors of the HLA system, update March 1997.

PMID- 9234499
TI  - Are Candida albicans natural populations subdivided?

PMID- 9234500
TI  - Virus entry: two receptors are better than one.

PMID- 9234501
TI  - T cells and memory lapses.

PMID- 9234502
TI  - Pathogenesis of gastric Helicobacter pylori.

PMID- 9234503
TI  - To sting or be stung: bacteria-induced apoptosis.

PMID- 9234504
TI  - The cag pathogenicity island: mechanistic insights.

PMID- 9234505
TI  - Bacterial phospholipases.

PMID- 9234506
TI  - HIV resources on the Web.

PMID- 9234507
TI  - Microbial genomes.

PMID- 9234508
TI  - Bacteriophage therapy and prophylaxis: rediscovery and renewed assessment of
      potential.
AB  - Bacteriophages were discovered 82 years ago. Claims for their use in the
      treatment of infections were not confirmed by early controlled trials, and the
      success of antibiotics superseded this potential use. However, recent studies
      have shown interesting therapeutic effects that warrant further investigation and
      development.

PMID- 9234509
TI  - How the Listeria monocytogenes ActA protein converts actin polymerization into a
      motile force.
AB  - The ActA protein is an essential determinant of pathogenicity that is responsible
      for the actin-based motility of Listeria monocytogenes in mammalian cells and
      cell-free extracts. ActA appears to control at least four functions that
      collectively lead to actin-based motility: (1) initiation of actin
      polymerization, (2) polarization of ActA function, (3) transformation of actin
      polymerization into a motile force and (4) acceleration of movement mediated by
      the host protein profilin.

PMID- 9234510
TI  - Antiviral activity of cyclopentenone prostanoids.
AB  - Cyclopentenone prostanoids inhibit virus replication by turning on an
      intracellular defence response that involves the induction of cytoprotective heat
      shock proteins, the modification of viral glycoprotein maturation and the control
      of NF-kappa B activation. These molecules represent an interesting model for the
      development of novel antiviral drugs that can affect different targets during the
      virus life cycle.

PMID- 9234511
TI  - Rho proteins: targets for bacterial toxins.
AB  - GTP-binding proteins of the Rho family are regulators of the actin cytoskeleton
      and molecular switches in various signal transduction pathways. The Rho proteins
      are targets for bacterial protein toxins that either inactivate GTPases by ADP
      ribosylation or glucosylation, or activate them by deamidation. Rho proteins play
      essential roles in host cell invasion by bacteria.

PMID- 9234512
TI  - Origins and functions of the chlamydial inclusion.
AB  - Chlamydiae dissociate themselves from the endocytic pathway shortly after
      internalization by actively modifying the vacuole to become fusogenic with
      sphingomyelin-containing exocytic vesicles. Interaction with this secretory
      pathway appears to provide a pathogenic mechanism that allows chlamydiae to
      establish themselves in a site that is not destined to fuse with lysosomes.

PMID- 9234513
TI  - Nucleic acid vaccines: an overview.

PMID- 9234514
TI  - Biological features of genetic immunization.
AB  - Genetic immunization (a.k.a. DNA-based immunization) shows promise at least as a
      convenient method to test and discover new vaccines and may be an efficient
      vaccine delivery system. However, relatively little is known about the parameters
      affecting its effectiveness, let alone its basic underlying biological
      mechanisms. Here we report on investigations of some of the factors that
      determine the quantity and quality of the immune response with genetic
      immunization. We find that for non-toxic proteins the antibody response
      correlates well with the level of expression as does the cellular response to a
      certain level. The augmentation of the immune response by co-introduction of a
      cytokine gene as a genetic adjuvant is also responsive to the expression level of
      the antigen. The immune response is inversely correlated to the age of the mice
      and at least part of this effect is through level of expression of the antigen.
      Gene gun administration of the transgene to the skin has the advantage over
      muscle injection in that ca 100-fold less DNA is required for the same level of
      expression and the injections are more reproducible in effect. Finally, the
      apparent differences in Th2 (gun) vs Th1 (muscle) responses between the two modes
      can at least partly be accounted for by differences in the amount of plasmid DNA
      typically administered.

PMID- 9234515
TI  - Expression and immunogenicity of Mycobacterium tuberculosis antigen 85 by DNA
      vaccination.
AB  - Plasmid DNA expression vectors encoding Mycobacterium tuberculosis antigen 85
      (Ag85) were tested as vaccines in preclinical animal models. Expression of
      secreted and nonsecreted forms of Ag85 was observed after transient transfection
      of cells in vitro. In mice, both types of Ag85 DNA constructs induced strong
      humoral and cell-mediated immune responses, as measured by ELISA of sera and
      recall responses of spleen cells restimulated in vitro, respectively, Therefore,
      DNA vaccination is an effective means of expressing mycobacterial proteins in
      eukaryotic cells leading to the induction of potent immune responses.

PMID- 9234516
TI  - Induction of cytotoxic T cell responses in newborn mice by DNA immunization.
AB  - Cytotoxic T cells (CTL) play a critical role in controlling viral infections.
      Infection of neonatal NFSIN mice with a high dose of Cas-Br-M murine leukemia
      virus, a neuropathogenic type C retrovirus, results in virus-induced neurologic
      disease and in their failure to generate a protective CTL response. Cas-Br-M
      specific CTL are necessary in the protection of neonatal mice from Cas-Br-M
      induced neurologic disease. Here we demonstrate that intramuscular inoculation of
      newborn mice with naked DNA expressing the full length Cas-Br-M genome induces a
      virus-specific CTL-mediated response. This CTL response is mediated by CD8+ T
      cells, is long lasting and, when transferred to susceptible neonatal recipients,
      protects them from Cas-induced neurologic disease. We also provide evidence that
      the intramuscular inoculation of neonates with plasmid DNA encoding only env
      sequences induces a dose-dependent CTL response in the absence of an anti-MuLV
      antibody response.

PMID- 9234517
TI  - Potential advantages and risks of nucleic acid vaccines for infant immunization.
AB  - Infant antibody responses are impaired due to defective B cell activation by
      bacterial polysaccharides, slow B cell responses to protein antigens and reduced
      T cell helper activities. These features result in a 'greater susceptibility to
      severe infections by encapsulated bacteria and the requirement for repeated doses
      of vaccines during the first years of life. Nucleic acid vaccines could optimize
      infant antibody responses by allowing the identification of novel protective
      antigens, by supplying missing cytokines, by the achievement of sustained immune
      responses or by the design of novel combination vaccines allowing a reduction of
      required injections. The deficient infant cellular immune responses, responsible
      for their susceptibility to infections with intracellular pathogens, could
      possibly benefit from the potential of nucleic acid vaccines to trigger strong
      TH1-like responses. Last, a major contribution to infant immunization would be
      achieved if nucleic acid vaccines proved able to circumvent maternal antibody
      mediated inhibition of infant responses to vaccine antigens.

PMID- 9234518
TI  - Development of improved vectors for DNA-based immunization and other gene therapy
      applications.
AB  - Optimizing gene expression and delivery are necessary steps in the production of
      vectors for DNA-based immunization as well as for other gene therapy
      applications. A mouse muscle/reporter gene assay system was used to
      systematically improve a plasmid DNA vector. The optimized vector VR1255
      contained: (1) CMV promoter and enhancer; (2) CMV IE Intron A; (3) kanamycin
      resistance gene; (4) deleted SV40 origin of replication; (5) optimized lux coding
      region; and (6) a minimal synthetic terminator from the rabbit beta globin gene,
      mRBG. The vector VR1255 expressed 137 times greater than an earlier prototype RSV
      based vector. For plasmid vector delivery into nonmuscle tissues, a recently
      synthesized cationic lipid, GAP-DLRIE, was found to greatly enhance the uptake
      and expression of plasmid DNA by 100-fold when instilled into the mouse lung. The
      time-course of CAT expression with GAP-DLRIE indicated that peak expression
      occurs 2-5 days after intranasal administration and expression diminished to
      about one-third the peak value by day 21. This cationic lipid may be useful for
      immunization by pulmonary and perhaps other nonmuscle routes.

PMID- 9234520
TI  - Genetic to genomic vaccination.
AB  - Our development of genetic immunization (unfortunately named 'DNA'-immunization
      at times) seems to have great promise as a vaccine delivery system. However, one
      is still left with the often formidable problem of discovering what gene of the
      pathogen to include in the genetic immunization vector. The is particularly a
      problem with pathogens with large genomes such as bacteria and parasites. We have
      developed a potential solution to this problem termed 'expression library
      immunization'. It involves using expression libraries in genetic immunization
      vectors to basically strip down the genome into protective genes. It may offer a
      systematic, unbiased approach to discover vaccine candidates.

PMID- 9234519
TI  - Attenuated bacteria as a DNA delivery vehicle for DNA-mediated immunization.
AB  - Previously, Shigella carrier 15D was shown to deliver a mammalian DNA expression
      plasmid to cultured cells with subsequent production of the plasmid-encoded
      foreign protein. In this study, we report in vivo delivery of a DNA expression
      plasmid to mucosal tissue results in the stimulation of immune responses against
      the plasmid-encoded foreign antigen. Splenocytes from mice receiving two
      intranasal inoculations of 15D carrying pCMV beta showed proliferative responses
      to the plasmid-encoded Escherichia coli beta-galactosidase. In addition, antibody
      specific for beta-galactosidase was detected in pooled sera collected from 15D
      (pCMV beta) infected mice.

PMID- 9234521
TI  - Mucosal immunization with DNA encoding influenza hemagglutinin.

PMID- 9234522
TI  - Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and
      mucosal antibody responses to encoded protein after oral administration.
AB  - We have developed a method for the encapsulation of plasmid DNA in poly(DL
      lactide-co-glycolide) microparticles. Encapsulated DNA, expressing the insect
      protein luciferase under the transcriptional control of the human cytomegalovirus
      immediate early promoter, was administered to mice by intraperitoneal injection
      or oral gavage. Intraperitoneal injection of encapsulated DNA elicited good serum
      IgG and IgM responses, and a modest IgA response. Oral administration stimulated
      good serum antibody responses in all three classes, and in addition, significant
      levels of mucosal IgA. PLG encapsulation thus has the ability to protect plasmid
      DNA against degradation after administration, and to facilitate its uptake into
      appropriate cells for the subsequent expression and presentation of antigen, in
      such a way as to elicit both systemic and mucosal antibody responses. These
      findings may have major implications for the design of novel vaccines and
      delivery strategies.

PMID- 9234523
TI  - Mucosal immunization with DNA-liposome complexes.
AB  - The mucosal surfaces represent the primary site for transmission of several
      viruses including HIV. To prevent mucosal transmission and dissemination to the
      regional lymph nodes, an effective HIV vaccine may need to stimulate immune
      responses at the genital and rectal mucosa. Optimal induction of mucosal immunity
      in general requires targeting antigens to the specialized antigen presenting
      cells of mucosal associated lymphoid tissues. The nasal mucosa may provide a
      simple, non-invasive route to deliver DNA encoding the introduced gene to
      stimulate mucosal immunity. As a first step to evaluate the feasibility of this
      approach, we have investigated as a model system, systemic and mucosal immune
      responses elicited to firefly luciferase generated by DNA immunization.
      Incorporating DNA into liposomes with cationic lipids enhanced luciferase
      expression in nasal tissue, and was associated with induction of a humoral
      response in serum and vaginal fluids and also a proliferative and cytotoxic T
      lymphocyte response in the spleen and iliac lymph nodes draining the genital and
      rectal mucosa.

PMID- 9234524
TI  - Mucosal immunization with a DNA vaccine induces immune responses against HIV-1 at
      a mucosal site.
AB  - Mucosal immunity is the first defense system in protection against mucosal
      infection by sexually transmitted diseases and subsequent systemic dissemination
      of infection. Development of vaccines which can induce protective mucosal
      immunity would have great promise for preventing sexually transmitted diseases
      including AIDS. DNA vaccines have recently shown certain advantages over other
      types of vaccines in safety and elicitation of specific immune responses. We have
      hypothesized that direct delivery of a DNA plasmid coding the HIV-1 envelope
      (pcMN160) via mucosal routes will stimulate mucosal immunity against HIV-1. The
      expression of DNA plasmid inoculated intravaginally was detected in various
      tissues. Intravaginal inoculation of pcMN160 elicits production of vaginal
      immunoglobulins which specifically bind to the HIV-1 envelope and neutralize HIV
      1 infectivity in vitro. These results indicate the feasibility of inducing
      mucosal immunity following mucosal inoculation of DNA vaccines. When coupled with
      systemic inoculation of appropriate DNA constructs, effective mucosal and
      systemic immunity may be generated.

PMID- 9234525
TI  - Immunization of mice with DNA encoding fragment C of tetanus toxin.
AB  - Immunization of mice with Fragment C protein, the non-toxic C-terminal domain of
      tetanus toxin, will protect mice against lethal challenge with tetanus toxin. A
      plasmid, pcDNA3/tetC, which encodes a synthetic tetC gene expressed under the
      control of the human cytomegalovirus major intermediate early promoter/enhancer
      region, was constructed. Fragment C expression was observed in Chinese hamster
      ovary cells following transfection with pcDNA3/tetC. The immune response induced
      by intramuscular immunization with pure pcDNA3/tetC DNA was evaluated in a murine
      model. Anti-Fragment C serum immunoglobulin and proliferative responses in
      splenocytes were observed following two immunizations with pcDNA3/tetC. The major
      IgG subclass that recognized Fragment C was IgG2a and the stimulated splenocytes
      secreted high levels of interferon-gamma. Sufficient anti-Fragment C serum
      immunoglobulins were induced by DNA-mediated immunization to protect mice against
      lethal challenge with tetanus toxin.

PMID- 9234526
TI  - Immunogenicity and efficacy of a tuberculosis DNA vaccine encoding the components
      of the secreted antigen 85 complex.
AB  - BALB/c and C57BL/6 mice were injected intramuscularly with plasmid DNA encoding
      the three components of the immunodominant 30-32 kDa antigen 85 complex (Ag85A,
      Ag85B, and Ag85C) from Mycobacterium tuberculosis culture filtrate, in order to
      investigate the utility of nucleic acid vaccination for induction of immune
      responses against mycobacterial antigens. Ag85A and Ag85B encoding plasmids
      induced a robust Th1-like response towards native Ag85, characterized by elevated
      levels of interleukin (IL)-2, interferon-gamma, and TNF-alpha. Levels of IL-4, IL
      6, and IL-10 were low or undetectable. Plasmid encoding Ag85C was not effective.
      Cytotoxic T cell activity was also generated in in vitro restimulated splenocyte
      cultures from Ag85A and Ag85B DNA vaccinated mice. Finally, Ag85A and Ag85B DNA
      vaccination conferred significant protection against mycobacterial replication in
      lungs from B6 mice, subsequently challenged. Therefore, this technique may be
      useful for the definition of protective antigens of M. tuberculosis and the
      development of a more effective tuberculosis vaccine.

PMID- 9234527
TI  - Protection against tuberculosis by a plasmid DNA vaccine.
AB  - Past attempts to use fractions of mycobacteria as an alternative to BCG have
      given disappointing results. The availability of cloned genes and suitable
      vectors has now opened a new avenue in which individual mycobacterial protein
      antigens are synthesised within transfected mammalian cells. In an ex vivo
      transfection approach with a retroviral vector we found that even a single
      antigen (hsp65) could evoke strong protection when expressed as a transgene and
      that expression of protection was largely a function of antigen specific
      cytotoxic T cells. We now find that intramuscular injection of plasmid DNA
      expressing the antigen from either a viral or a murine promoter can also give
      protection equivalent to Bacillus Calmette-Guerin (BCG). Plasmids expressing some
      other mycobacterial antigens, hsp70, 36 kDa and 6 kDa, are also effective,
      suggesting that this approach may lead to a new vaccine.

PMID- 9234528
TI  - Expression of a viral protein by muscle cells in vivo induces protective cell
      mediated immunity.
AB  - Intramuscular injection of plasmid DNA expression vectors results in transfection
      of myocytes in situ. To determine whether expression of antigen by myocytes is
      sufficient to induce protective cell-mediated immunity, stably transfected
      myoblasts expressing influenza nucleoprotein (NP) were transplanted into mice.
      These animals produced high-titer anti-NP antibodies and MHC class I-restricted
      cytotoxic T lymphocytes, and were protected from a cross-strain lethal challenge
      with influenza A virus. Therefore, antigen expression by muscle cells in vivo is
      sufficient to confer protective cell-mediated immunity.

PMID- 9234529
TI  - Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine
      for human use.
AB  - Data generated in the Plasmodium yoelii rodent model indicated that plasmid DNA
      vaccines encoding the P.yoelii circumsporozoite protein (PyCSP) or 17 kDa
      hepatocyte erythrocyte protein (PyHEP17) were potent inducers of protective CD8+
      T cell responses directed against infected hepatocytes. Immunization with a
      mixture of these plasmids circumvented the genetic restriction of protective
      immunity and induced additive protection. A third DNA vaccine encoding the P.
      yoelii sporozoite surface protein 2 (PySSP2) also induced protection. The P.
      falciparum genes encoding the homologues of these three protective P. yoelii
      antigens as well as another P. falciparum gene encoding a protein that is
      expressed in infected hepatocytes have been chosen for the development of a human
      vaccine. The optimal plasmid constructs for human use will be selected on the
      basis of immunogenicity data generated in mice and nonhuman primates. We
      anticipate that optimization of multi-gene P. falciparum DNA vaccines designed to
      protect against malaria by inducing CD8+ T cells that target infected hepatocytes
      will require extensive clinical trials during the coming years.

PMID- 9234530
TI  - DNA-based vaccination using Schistosoma japonicum (Asian blood-fluke) genes.
AB  - We have examined the efficacy of nucleic acid vaccination in inducing immunity to
      the multicellular parasite, Schistosoma japonicum, a trematode worm responsible
      for causing schistosomiasis in humans and other mammalian species. A panel of
      Schistosoma japonicum cDNAs were cloned into eukaryotic expression vectors,
      injected into animals, and tested for immunogenicity. The cDNAs tested encoded 26
      and 28-kDa glutathione-S-transferases, calreticulin, glyceraldehyde-3-phosphate
      dehydrogenase, a 22.6 kDa membrane-associated antigen, a 14 kDa fatty-acid
      binding protein, fragments of paramyosin, full-length paramyosin, and a novel
      gene comprising the 26 kDa glutathione-S-transferase fused to a fragment of
      paramyosin cDNA. The paramyosin gene constructs, including the fusion, were all
      able to induce anti-paramyosin antibodies; with the fragments of paramyosin these
      were of the IgG1, IgG2a and IgG2b isotypes. In contrast, none of the other
      schistosome cDNAs tested were able to induce detectable antibody responses. The
      anti-paramyosin antibodies did not protect mice challenged with cercariae of S.
      japonicum.

PMID- 9234531
TI  - DNA-based immunization against hepatitis B surface antigen (HBsAg) in normal and
      HBsAg-transgenic mice.
AB  - Hepatitis B virus (HBV) remains a serious worldwide health problem and the
      possibility to control it will depend on the availability of safe, effective and
      affordable vaccines. Recombinant protein or plasma-derived vaccines containing
      HBV surface antigen (HBsAg) are safe and generally efficacious, however, they are
      too expensive for widespread use in areas of HBV endemicity and are only
      partially effective for treatment of HBV chronic carriers. Immunization of mice
      by injection of HBsAg-expressing plasmid DNA results in rapid induction of strong
      and long-lasting humoral and cell-mediated immune responses. Here we report
      optimization of the humoral response with the use of necrotizing agents, co
      expression of cytokines or co-stimulatory molecules and formulation of the DNA
      with cationic liposomes. DNA-based immunization of HBsAg-transgenic mice can also
      overcome non-response to HBsAg. Thus, DNA vaccines against HBV may be useful for
      both prophylactic and therapeutic purposes.

PMID- 9234532
TI  - DNA vaccination for the induction of immune responses against hepatitis C virus
      proteins.
AB  - Recent analysis of clinical and experimental cases of hepatitis C virus (HCV)
      infection suggest the possible role of the viral nucleocapsid (C), the
      nonstructural protein 3 (NS3) and the envelope glycoproteins E1 and/or E2 in the
      mounting of immune responses capable to control infection (Botarelli et al.,
      Gastroenterology, 1993, 104, 580-587; Choo et al., Proc. Natl Acad. Sci. USA,
      1994, 91, 1294-1298). We have used DNA-based immunization to study the immune
      responses that can be induced by injecting DNA-derived immunogens encoding C and
      E2 sequences. Comparative analysis were performed in mice using expression
      plasmids containing full-length or partial gene sequences cloned in fusion with
      the hepatitis B virus surface antigen (HBV-HCV chimeras). The results obtained
      indicate that: (1) anti-C and anti-E2 antibodies can be induced with all
      constructs including the HBV-HCV chimeras; (2) titers range from 1:100 to
      1:100000 depending on the antigen and nucleotide sequence context; (3) all HCV
      DNA immunogens are associated with a predominant Th1 response; (4) CTL can be
      detected against both HCV and HBV determinants.

PMID- 9234533
TI  - The prophylactic effect of immunization with DNA encoding herpes simplex virus
      glycoproteins on HSV-induced disease in guinea pigs.
AB  - Plasmid expression vectors encoding herpes simplex virus type 2 (HSV-2)
      glycoproteins B (gB) or D (gD) were constructed and tested for their ability to
      immunize guinea pigs against genital HSV infection. Immunization with a plasmid
      expressing the aminoterminal 707 amino acids (aa) of gB induced humoral immune
      responses detected by ELISA and virus neutralization. When challenged by vaginal
      infection, immunized animals were partially protected from genital herpes,
      exhibiting significantly reduced primary and subsequent recurrent disease. When
      the gB plasmid was combined with a plasmid expressing full-length gD, immunized
      guinea pigs developed humoral responses to both proteins and were also
      significantly protected from viral challenge.

PMID- 9234534
TI  - Polynucleotide vaccines in animals: enhancing and modulating responses.
AB  - We immunized cattle, the natural host for bovine herpesvirus 1 (BHV-1), with a
      polynucleotide vaccine encoding BHV-1 glycoprotein D. These cattle trials clearly
      indicate that large species can be immunized with polynucleotide vaccines.
      Recently, using a murine model, we demonstrated that: the cellular compartment to
      which the expressed antigen is delivered determines the type of immune response
      (type 1 or type 2), and that the magnitude and direction of the immune response
      can be modulated by coadministration of plasmid encoded cytokines and antigen.
      Finally, we demonstrated that immunization of mice with a polynucleotide vaccine
      encoding BHV-1 gD could circumvent preexisting passively transferred, gD
      specific, polyclonal antisera and lead to the development of an active immune
      response.

PMID- 9234535
TI  - Further protection against antigenic drift of influenza virus in a ferret model
      by DNA vaccination.
AB  - Previously we showed that immunization of ferrets with DNA encoding the
      hemagglutinin (HA), nucleoprotein (NP), and matrix protein (M1) of influenza
      virus induced protective immune responses. A DNA vaccine encoding HA (from a 1991
      strain), NP and M1 (from a 1989 strain) protected ferrets better against
      challenge with the antigenic drift variant A/Georgia/03/93 than did the
      inactivated vaccine from the 1992-93 influenza season. Here we report that the
      same DNA vaccine protected ferrets against a second, further divergent, drift
      variant (A/Johannesburg/33/94). Furthermore, the extent of protection provided by
      the DNA vaccine was equivalent to the homologous protection provided by an
      inactivated vaccine that exactly matched the challenge strain.

PMID- 9234536
TI  - Vaccination with HIV-1 gp120 DNA induces immune responses that are boosted by a
      recombinant gp120 protein subunit.
AB  - Small animals were immunized with plasmid DNA encoding HIV-1 envelope gp120
      either intramuscularly by needle injection (mice and guinea pigs) or epidermally
      with the Accell gene gun (guinea pits). Subsequently, the animals were boosted
      with a recombinant gp120 protein subunit vaccine in an oil-in-water based
      adjuvant, MF59. Antibodies and cytotoxic T-lymphocyte (CTL) immune responses to
      the HIV envelope glycoprotein were observed in animals immunized with gp120 DNA
      derived from the HIV-1SF2 laboratory strain or from HIV-1 field isolates. Titers
      of ELISA antibodies and serum neutralizing antibodies against the HIV-1SF2
      laboratory isolate were substantially increased in DNA-immunized animals
      following a single boost with recombinant gp120 protein subunit. This DNA
      prime/protein subunit boost immunization approach may be important for
      vaccination against infectious agents such as HIV for which it is difficult to
      raise strong antiviral humoral responses with DNA vaccination alone.

PMID- 9234537
TI  - Nucleic acid vaccination with HIV regulatory genes: a combination of HIV-1 genes
      in separate plasmids induces strong immune responses.
AB  - The concept of combining several genes in order to immunize against a microbial
      agent has been tested. We selected human immunodeficiency virus (HIV) genes that
      individually have been shown to mediate immune responses against HIV proteins.
      These proteins were the regulating genes/proteins of HIV-1 rev, tat and nef as
      well as structural genes for gp160 under the control of rev, and the capsid p24
      represented by the larger precursor gene p37. Two findings were of particular
      interest. The combination of these five gene constructs gave strong reactivity to
      all of them, compared with previous results using each one in single injections.
      The intranasal immunization route gave good mucosal reactivity by inducing IgG,
      IgA and T-cell proliferative responses.

PMID- 9234538
TI  - Development of a multicomponent candidate vaccine for HIV-1.
AB  - Nucleic acid or DNA immunization represents a novel approach to both vaccine and
      immune therapeutic development. DNA vaccination induces antigen-specific cellular
      and humoral immune responses through the delivery of non-replicating
      transcription units which drive the synthesis of specific foreign proteins within
      the inoculated host. We have previously reported on the potential use of DNA
      immunization as a novel vaccine strategy for HIV-1. We found that both antigen
      specific cellular and humoral immune responses could be induced in vivo with
      various DNA vaccine constructs against different antigenic targets within HIV-1.
      In order to enhance the DNA vaccine's ability to elicit cell-mediated immune
      responses, we co-delivered plasmids encoding costimulatory molecule B7 and
      interleukin-12 genes with DNA vaccine for HIV-1. We observed a dramatic increase
      in both antigen-specific T helper cell proliferation and CTL response. Eventual
      development of successful vaccines for HIV-1 would likely involve targeting
      multiple antigenic components of the virus to direct and empower the immune
      system to protect the host from viral infection. We present here the utility of
      multicomponent DNA immunization to elicit specific humoral and cell-mediated
      immune responses against different antigenic targets of HIV-1 as well as the
      ability of this immunization strategy to achieve significant enhancements of
      antigen-specific cellular immune responses.

PMID- 9234539
TI  - Anti-HIV env immunities elicited by nucleic acid vaccines.
AB  - Plasmid DNA vaccines encoding HIV-1 env were used to immunize mice and nonhuman
      primates. Plasmids were prepared that produced either secreted gp120 or full
      length gp160. Mice immunized with gp120 DNA developed strong antigen-specific
      antibody responses, CD8+ cytotoxic T lymphocytes (CTL) (following in vitro
      restimulation with gp120-derived peptide), and showed in vitro proliferation and
      Th1-like cytokine secretion [gamma-interferon, interleukin (IL)-2 with little or
      no IL-4] by lymphocytes obtained from all lymphatic compartments tested (spleen,
      blood, and inguinal, iliac, and mesenteric lymph nodes). This indicated that
      systemic anti-gp120 cell-mediated immunity was induced by this DNA vaccine.
      Although similar antibody responses were observed in mice immunized by either
      intramuscular or intradermal routes, T cell responses were significantly stronger
      in mice injected intramuscularly. Rhesus monkeys immunized with both gp120 and
      gp160 DNAs exhibited significant CD8+ CTL responses, following in vitro
      restimulation of peripheral blood lymphocytes with antigen. These experiments
      demonstrate that DNA immunization elicits potent immune responses against HIV env
      in both a rodent and a nonhuman primate species.

PMID- 9234540
TI  - Early studies on DNA-based immunizations for measles virus.
AB  - DNA-mediated immunizations have been used to raise neutralizing antibodies for
      measles virus. Single inoculations of plasmids expressing measles hemagglutinin
      or fusion glycoproteins raised neutralizing antibody in BALB/c mice. Plasmids
      expressing the hemagglutinin glycoprotein (both normal and secreted) raised
      neutralizing responses that persisted for 1 year. For both forms of
      hemagglutinin, the effectiveness of the raised antibody (ratio of neutralizing
      activity to ELISA activity) was similar. High titers of neutralizing antibody
      were also raised by inoculation of rabbits with the hemagglutinin and fusion
      glycoprotein-expressing plasmids.

PMID- 9234541
TI  - Nanogram quantities of plasmid DNA encoding the rabies virus glycoprotein protect
      mice against lethal rabies virus infection.
AB  - Vaccination against virus infections has proven to be an effective strategy in
      the improvement of human health. In this study, we evaluated two plasmid DNA
      vaccines expressing the glycoprotein (G) gene of the challenge virus standard
      (CVS) rabies virus for their ability to elicit neutralizing antibody and protect
      BALB/cByJ mice against lethal rabies virus challenge. A single inoculation of 10
      micrograms of plasmid DNA encoding G protected 100% of the intramuscularly (i.m.)
      vaccinated mice, and 0.1 microgram of DNA protected 83% of the intradermally
      (i.d.) vaccinated mice. All mice that survived had serum anti-rabies virus
      neutralizing antibody titers > or = 1:40 prior to virus challenge. The highest
      antibody titers were detected in mice that had been inoculated i.m. with 10-100
      micrograms of DNA in regenerating muscle. The immunostimulant monophosphoryl
      lipid A enhanced the neutralizing antibody response of i.d.-vaccinated mice. Anti
      rabies virus neutralizing antibody elicited by plasmid DNA vaccination cross
      neutralized a global spectrum of rabies virus variants. These results indicate
      that DNA vaccines could be a solution for providing developing countries with an
      inexpensive vaccine that is simple to prepare, is highly efficacious and has
      excellent stability.

PMID- 9234542
TI  - The effect of interferon-gamma on genetic immunization.
AB  - The effect of co-inoculation of a plasmid vector expressing the rabies virus
      glycoprotein and an additional vector encoding mouse interferon (IFN)-gamma on
      the development of an antigen specific B and T helper cell response was tested
      upon intramuscular inoculation of mice. The effect of IFN-gamma was dependent on
      the promoter driving expression of the viral antigen. The immune responses to
      antigen-expressing vector carrying a viral promoter such as the SV40 early
      promoter or the major histocompatibility (MHC) class I promoter were reduced in
      presence of IFN-gamma while the B and T helper cell response to a vector
      expressing the antigen under the control of the MHC class II promoter was not
      affected by this cytokine.

PMID- 9234543
TI  - Protective immunity induced by rotavirus DNA vaccines.
AB  - It is estimated that Group A rotavirus diarrhea causes as many as one million
      deaths per year in children worldwide, and effective vaccines will be essential
      for their control. Plasmid DNA vaccines encoding murine rotaviral proteins VP4,
      VP6, or VP7 were tested in adult BALB/c mice for their ability to induce immune
      responses and provide protection against rotavirus challenge. The vaccines were
      administered by inoculation into cells of the epidermis with an Accell gene gun.
      (Auragen, Inc., Middleton, WI, USA). Each vaccine elicited rotavirus-specific
      serum antibodies as measured by ELISA. Virus neutralizing antibodies were
      detected in mice receiving plasmid DNAs encoding for outer capsid proteins VP4
      and VP7, but not for VP6, an inner capsid protein, and all of the vaccines
      generated virus-specific CTL responses. Each vaccine was effective in protecting
      mice against infection after homotypic rotavirus (100 ID50) challenge, showing
      reductions (P < 0.0002) in viral excretion measured over a 9 day period.
      Increased rotavirus-specific intestinal IgA antibodies were seen in vaccinated
      mice after rotavirus challenge, particularly in mice that received the VP6 DNA
      vaccine. This suggests that intracellular IgA-mediated neutralization may be
      involved in protective immunity induced by the VP6 DNA vaccine, and may represent
      a new mechanism for protection by DNA vaccines.

PMID- 9234544
TI  - Nonhuman primate models to evaluate vaccine safety and immunogenicity.
AB  - When considering preclinical studies to evaluate the safety and immunogenicity of
      putative vaccine candidates, such as nucleic acid vaccines, species most closely
      related to humans should be considered. Phylogenetically, the great apes
      (chimpanzees, orangutans, gorillas, and gibbons) are most closely related to
      humans. However, the great apes, which diverged from humans over 5 million years
      ago, represent endangered or threatened species that limits their utility in
      preclinical studies. In addition, cost considerations for using great apes in
      biomedical studies represents another serious limitation. The Old World monkeys,
      (macaques, baboons, mandrills, and mangabeys), diverged from humans over 15
      million years ago. A number of the Old World monkey species including rhesus,
      cynomolgus, and African green monkeys, have also been employed in biomedical
      research to evaluate vaccine safety and immunogenicity. New World monkeys (aotus,
      owl, cebus monkeys, and marmosets) are the most phylogenetically divergent from
      humans, yet they have also been utilized to develop nonhuman primate models for a
      number of human infectious diseases and tumors. The advantages and disadvantages
      in selecting a particular nonhuman primate species for studies to evaluate DNA
      vaccine safety and immunogenicity are briefly discussed. Comparative immunology,
      reproductive physiology, endogenous infectious agents, and cost considerations
      are briefly described.

PMID- 9234545
TI  - Immunization of non-human primates with DNA vaccines.
AB  - The pre-clinical efficacy of DNA vaccines has been demonstrated in a number of
      animal models, but more limited data exist regarding their immunogenicity in non
      human primates. The studies described below demonstrate that DNA vaccines in
      reasonable dosages encoding a variety of viral proteins could result in the
      generation of antibodies, neutralizing antibodies, or cytotoxic T lymphocytes in
      primates. Furthermore, these responses could be boosted by repeat administration
      of the DNA vaccine. In an effort to assess the safety of such vaccines sera from
      primates was shown to lack anti-DNA antibodies.

PMID- 9234546
TI  - Malaria DNA vaccines in Aotus monkeys.
AB  - In preparation for the development of DNA vaccines designed to produce protective
      antibodies against Plasmodium falciparum antigens (Ag), we conducted studies to
      optimize antibody responses in Aotus monkeys after immunization with the P.
      yoelli circumsporozoite (CSP) DNA vaccine. We demonstrate in Aotus monkeys that
      an intradermal route of immunization with a PyCSP plasmid DNA vaccine generates
      antibody responses equivalent to a multiple antigen peptide/adjuvant based
      vaccine, and that these data support the use of the intradermal route for initial
      studies of the efficacy of DNA vaccines in inducing protective antibodies against
      P. falciparum antigens in Aotus monkeys.

PMID- 9234547
TI  - Successful nucleic acid based immunization of newborn chimpanzees against
      hepatitis B virus.
AB  - To determine whether DNA based immunization could protect newborn chimpanzees
      against a challenge infection with hepatitis B virus, two chimpanzees were
      immunized on the day of birth with a plasmid coding for hepatitis B surface
      antigen, and boosted at 6 and 24 weeks. Both animals produced transient antibody
      to the hepatitis B surface antigen. Following challenge with hepatitis B virus at
      33 weeks the two immunized animals developed anamnestic antibody responses,
      however, neither developed detectable hepatitis B surface antigen or antibody to
      the core protein, the conventional markers of hepatitis B infection. Both of
      these markers appeared in an unimmunized control animal. We conclude that DNA
      based immunization can induce protective immunity in newborn chimpanzees.

PMID- 9234548
TI  - SIV DNA vaccine trial in macaques: post-challenge necropsy in vaccine and control
      groups.
AB  - In this study we describe the histopathologic findings from nine macaques in a
      simian immunodeficiency virus (SIV) DNA vaccine trial evaluating the ability of a
      5-plasmid DNA vaccine to protect against an uncloned SIVmac251 challenge (Lu et
      al., J. Virol. 1996, 70, 3978-3991). Three vaccinated and one control macaque
      developed disease and were euthanized in the first year following challenge. The
      other four vaccinated and one control macaque remained clinically normal and were
      euthanized at the end of the trial (60 weeks post-challenge). The necropsy data
      revealed that both diseased and clinically normal macaques had developed typical
      SIV-related lymphoid changes, inflammatory disorders and opportunistic
      infections. All animals had variable degrees of follicular and/or paracortical
      lymphoid hyperplasia suggesting immune activation. All but one vaccinated macaque
      and both control macaques had SIV-associated opportunistic infections. Within the
      small groups of animals, the ability to contain opportunistic infections was
      superior, and the overall lymphoid changes less severe, in the macaques that had
      received vaccine DNAs by three routes of inoculation (intravenous, intramuscular
      and gene gun) than in those that had received control DNAs or vaccine DNAs by
      gene gun only. In the future it will be important to further test how the route
      and method of DNA inoculation impact the efficacy of immunodeficiency virus
      vaccines.

PMID- 9234549
TI  - Enhancement of immunodeficiency virus-specific immune responses in DNA-immunized
      rhesus macaques.
AB  - In contrast to results obtained with plasmid DNA vectors encoding antigens from
      viruses such as influenza and hepatitis B, plasmids coding for antigens from
      primate immunodeficiency viruses have elicited relatively weak antibody responses
      following gene gun-mediated DNA immunization of rhesus monkeys. In an effort to
      augment these responses, the importance of the immunization schedule was
      investigated, as well as the possible synergy that might result from boosting
      gene gun-primed animals with other routes of immunization. Here we demonstrate
      that endpoint gp120-specific antibody titers can be enhanced as much as tenfold
      by reducing the number of immunizations and lengthening the resting period
      between immunizations. In addition, boosting gene gun-primed animals with either
      recombinant subunits or gp120-expressing vaccinia recombinants resulted in
      synergistic responses.

PMID- 9234550
TI  - Nucleic acid immunization of chimpanzees as a prophylactic/immunotherapeutic
      vaccination model for HIV-1: prelude to a clinical trial.
AB  - Vaccine development strategies have often utilized recombinant envelope
      glycoproteins which usually generate strong humoral immune responses but which do
      not generate strong cytotoxic T lymphocytes (CTL). A recent novel experimental
      vaccination approach involves the technology known as nucleic acid immunization
      in which DNA plasmids expressing a gene of interest is injected intramuscularly
      in experimental animals. These expressed proteins then are presented to the
      immune system with the subsequent development of strong antibody and cellular
      (particularly CTL) immune responses. These types of immune responses have been
      elicited in rodents as well as nonhuman primates including chimpanzees. Results
      from studies on nucleic acid immunization of HIV-1 infected chimpanzees with
      envelope glycoprotein expressing constructs indicated that this method was able
      to decrease substantially HIV-1 viral load in these chimpanzees. These data are
      useful for the development and implementation of human phase I clinical trials
      with HIV constructs expressing various genes from the HIV-1 genome.

PMID- 9234551
TI  - Simulated airborne spread of Aujeszky's disease and foot-and-mouth disease.
AB  - The atmospheric dispersion of virus was simulated using a computer model which
      had been developed for predicting the dispersion of toxic gases from chemical
      engineering plants. The results were compared with data from four outbreaks in
      which virus was believed to have been transported by air: two outbreaks of foot
      and-mouth disease in the United Kingdom in 1967 and outbreaks of Aujeszky's
      disease in Yorkshire in 1981 to 1982 and Indiana in 1988. There was relatively
      good agreement with most of these data. The paper shows that the model could be
      useful in an emergency because the risk of virus spread could be predicted in
      real time.

PMID- 9234552
TI  - Long-term ultrasonographic and venographic study of the development of tarsal
      vein thrombosis in a cow.
AB  - The development of thrombosis of three tarsal veins in a cow was studied by
      repeated ultrasonographic and venographic examinations for nine months. The
      venous diameter, the echogenicity of the thrombi and the sequential venographic
      findings were evaluated. Initially, the thrombosed parts of the ramus cranialis
      and caudalis of the vena saphena lateralis and the ramus caudalis of the vena
      saphena medialis had greatly increased diameters and were not compressible. The
      thrombi appeared as poorly echogenic masses. Within five months, the diameters of
      the occluded veins had decreased to almost normal dimensions. The echogenicity of
      the thrombi diminished at their distal and proximal ends. The length of the
      thrombi was decreased by up to 6.5 cm. However, the thrombosed veins did not re
      open. One year after diagnosis, the cow was culled and the persistence of the
      venous thromboses was confirmed.

PMID- 9234553
TI  - Elimination of Salmonella typhimurium infection by the strategic movement of
      pigs.
AB  - Three field investigations were carried out to assess the feasibility of raising
      salmonella-free finishers from pigs born in infected herds, by moving the pigs to
      clean and disinfected facilities before their expected exposure to the bacteria
      from the environment. Three herds with persistently high levels of subclinical
      infection with S typhimurium in the finishing pigs were used. They practised all
      in all-out management in the nurseries and in the grower units. A total of 844
      pigs were moved, either at weaning, from the nursery, or from the grower unit to
      newly built or rigorously cleaned and disinfected finishing units with no known
      history of salmonella infection. No detectable infection was observed at
      slaughter either serologically or bacteriologically by random testing of the pigs
      which had been moved, whereas a proportion of the pigs raised at the same time in
      the continuous systems on the farms were found to be infected.

PMID- 9234554
TI  - Gas bubble disease in farmed fish in Saudi Arabia.
AB  - Four outbreaks of gas bubble disease were encountered among farmed fish in Saudi
      Arabia. Two of them occurred among subadult (52.5 g) saltwater tilapia
      (Oreochromis spilurus), the first affecting about 50 per cent of the stock and
      resulting in about 30 per cent mortality, and the second affecting about 25 per
      cent of the population with about 5 per cent mortality. Another outbreak occurred
      among adult (270 g) brackish water (0.5 per cent salinity) tilapia (Oreochromis
      niloticus), affecting about 40 per cent of the population with about 25 per cent
      mortality. The fourth outbreak occurred among three-month-old (15 g) grouper
      (Epinephelus fuscogutiatus) and resulted in 10 per cent mortality. In all cases
      the total water gas pressure ranged between 111.2 and 113.4 per cent saturation
      and nitrogen was supersaturated while oxygen was undersaturated. The outbreaks
      were alleviated by reducing the gas pressure by splashing the source water or by
      switching to a source of water with lower gas pressure. However, in O niloticus
      the conditions of gas supersaturation resulted in a heavy infection by
      monogenetic trematodes which was treated with formalin at 40 mg/litre for seven
      hours on five successive days.

PMID- 9234555
TI  - Ocular disease associated with silage feeding and Listeria monocytogenes in
      fallow deer.

PMID- 9234556
TI  - Virulent foot rot in sheep.

PMID- 9234557
TI  - 'Gut-tie' in steers.

PMID- 9234558
TI  - Use of rabbits in ostrich rearing.

PMID- 9234559
TI  - Erectile dysfunction in premature ejaculation.
AB  - Between October 1993 and December 1995, 45 patients with premature ejaculation
      were included in this study. The patients were divided into two groups
      etiologically, as having primary or secondary ejaculation. After a complete
      laboratory evaluation all patients underwent papaverine tests color Doppler
      ultrasonography pharmacocavernosometry-cavernosography and consequently organic
      etiology were investigated. Venous leakage was found in 5 (22,7%), arterial or
      mix insufficiency in 2 (9%) of the patients with primary premature ejaculation.
      In secondary premature ejaculation group, venous leakage was encountered in 9
      patients (39,1%), arterial insufficiency in 2 patients (8,6%). In conclusion,
      investigation of organic etiology for the patients with premature ejaculation,
      particularly with secondary premature ejaculation, seems to be beneficial for
      correct diagnosis.

PMID- 9234560
TI  - Aberrant adrenal cortical tissue adjacent to immature testis.

PMID- 9234561
TI  - The value of cavernous body biopsy in evaluating of impotent men.
AB  - Rapid advances in the basic understanding of the anatomy, physiology and
      pharmacology of penile erection have drastically changed the clinical approach to
      patients with erectile dysfunction. To evaluate the value of microscopic
      architecture of the corpora cavernosa, we examined cavernous body biopsies taken
      during penile prosthesis implants. We studied on 12 impotent patients 25 to 67
      years old who underwent implantation of a penile prosthesis. The biopsy was
      stained with H&E (Hematoxylin and Eosin) for general architecture, Masson
      Trichrome for collagen distribution and EVG for elastic fibers. Except 3 cases no
      pathological changes were determined at H&E staining. At collagen staining,
      roughly increased collagen distribution was determined in all cases. There were
      no appreciable differences in distribution of elastic fibers. In conclusion our
      data demonstrate that cavernous body biopsy is of limited value to determine
      etiologic factors in patients with erectile dysfunction.

PMID- 9234562
TI  - Transurethral incision of prostate (TUIP) and retrograde ejaculation.
AB  - OBJECTIVE: Men of any age with bladder outlet obstruction and without measurable
      enlargement of the prostate constitute ideal candidates for TUIP. Effectiveness
      of any technique with respect to flow rate improvement is firmly established,
      indifferently whether unilateral or bilateral. But there is a wide variation in
      the reported incidence of retrograde ejaculation with unilateral and bilateral
      incision. MATERIAL AND METHODS: The retrospective analysis of our 45/57 available
      patients treated with this technique, between January 1993 and March 1995, does
      not show a major incidence of this complication for the bilateral incision, with
      an overall incidence of 6.6% (3/45 patients). CONCLUSIONS: Although ejaculation
      may be preserved, it cannot be guaranteed.

PMID- 9234563
TI  - Ureteroscopy and stone lithotripsy with lithoclast: personal experience.
AB  - Ureteroscopy has become a common technique in the diagnosis and treatment of
      ureteral pathologies, but this procedure is quite invasive and some complications
      have been reported in literature. In our Institute 49 patients underwent
      ureteroscopy and ballistic lithotripsy with lithoclast for ureteral stones. The
      stones were localized both in the middle and distal part of the ureter. We used a
      small caliber 7-8.5 Wolf ureteroscope. The treatments were performed under
      antibiotic prophylaxis. Direct access to the ureter without dilation of the
      meatus was obtained in 97.96% of patients. The stones were easily reached in
      93.88% of the cases and satisfactory fragmentation was obtained in 90.7%. In 4
      patients (9.3%) one or more large stone fragments escaped into the kidney,
      requiring the patients to be treated with ESWL. No major complications occurred:
      no ureteral perforations, no important bleeding and no severe or persistent
      infections. All patients were discharged in one to four days postoperatively. The
      authors conclude that ureteroscopy using small caliber instruments with
      Lithoclast is a safe and satisfactory alternative to ESWL in the treatment of
      ureteral stones.

PMID- 9234564
TI  - High-altitude pulmonary edema. Mechanisms and management.

PMID- 9234565
TI  - Diagnosing pulmonary embolism: noninvasive strategies.

PMID- 9234566
TI  - Cardiopulmonary exercise testing for heart transplant candidate selection.

PMID- 9234567
TI  - Effects of transdermal nitroglycerin on left ventricular function after acute
      myocardial infarction.
AB  - Progressive left ventricular dysfunction in acute myocardial infarction patients
      is associated with a poor prognosis. It has been shown that some therapeutic
      measures which have the potential for limiting the infarct size and preserving
      ventricular function, are also able to reduce the incidence of congestive heart
      and improve survival. The aim of this protocol was to assess the effects of
      transdermal nitroglycerin administered within 72 hours after the onset of acute
      myocardial infarction and for the following 6 months, on left ventricular
      function. A total of 98 consecutive acute myocardial infarction patients were
      randomly allocated, within 72 hours of onset of symptoms, to a double-blind 6
      month-therapy with either 10 mg/24 hour transdermal nitroglycerin or placebo.
      Patients underwent two-dimensional echocardiography at entry, after 2 weeks, 3
      months and 6 months. In the nitroglycerin group, end-diastolic volume increased
      during the follow-up (+6.7%, p < 0.05) while end-systolic volume remained nearly
      unchanged; ejection fraction and stroke volume increased progressively (+6.3%, p
      < 0.05, +14.2%, p < 0.05, respectively) and a important reduction of percent of
      dyssynergic segments was present (-19.2%, p < 0.005). In the placebo group end
      diastolic volume and end-systolic volume slightly increased during the follow-up
      (+2% and +4.9% respectively); ejection fraction and stroke volume remained nearly
      unchanged during the study; percent of dyssynergic segments showed an important
      decrease after 2 weeks and 6 months (-21.3%, p < 0.005). A clinically relevant
      increase (> 20%) in ejection fraction was present more frequently in the
      nitroglycerin than in the placebo group (p < 0.001). In conclusion, the early
      (within 72 hours) and prolonged (6 months) administration of transdermal
      nitroglycerin in acute myocardial infarction improves ejection fraction and
      stroke volume but does not modify ventricular remodeling.

PMID- 9234568
TI  - Silent thalassemias.

PMID- 9234569
TI  - The role of thrombolytic therapy in the treatment of pulmonary embolism.

PMID- 9234570
TI  - Telomerase activity in human hematopoietic progenitor cells.
AB  - BACKGROUND AND OBJECTIVE: Telomerase is the enzyme that stabilizes and elongates
      the telomeric ends of chromosomes. It is expressed in germline and malignant
      cells and absent in most human somatic cells. The selective expression of
      telomerase has thus been proposed to be a basis for the immortality of germline
      and malignant cells. Recently, telomerase activity has been observed in human
      bone marrow (BM) and peripheral blood (PB) samples. The objective of our study
      was to further characterize the telomerase-expressing population in BM and PB.
      METHODS: CD34+ cells were isolated from BM and PB, cultured in vitro, and
      telomerase activity was assessed by the PCR-based TRAP assay. RESULTS: Telomerase
      activity in human BM and PB could be almost exclusively assigned to the
      hematopoietic progenitor cell fraction expressing the CD34 antigen. We observed
      telomerase activity in CD34+ cells from BM and cytokine-mobilized PB. CD34+ cells
      lacking co-expression of CD33 demonstrated higher levels of telomerase than
      myeloid committed CD34+/CD33+ cells. In vitro culture of CD34+ cells in the
      presence of a cocktail of growth factors inducing differentiation resulted in a
      decrease of telomerase activity. Telomerase activity increased in peripheral
      blood during cytokine-induced mobilization of hematopoietic progenitor cells.
      INTERPRETATION AND CONCLUSIONS: Our data demonstrate that at least a portion of
      the hematopoietic stem/progenitor cell fraction expresses telomerase and
      downregulates its expression through differentiation.

PMID- 9234571
TI  - Silent thalassemias: genotypes and phenotypes.
AB  - BACKGROUND AND OBJECTIVE: Current application of molecular biology techniques to
      the study of the DNA of globin genes has confirmed the existence of silent alpha
      and beta thalassemias; which had already been reported on the basis of red blood
      cell parameters and family studies. The present work was aimed at analyzing all
      the aspects of the phenotype of the most common varieties of silent thalassemia.
      MATERIALS AND METHODS: Groups of heterozygous carriers of these varieties were
      examined using established techniques that determined all hematologic, hemoglobin
      (electrophoresis and measurement of Hb A2 and Hb F levels), and globin synthesis
      (evaluation of the alpha/beta ratio) parameters. Furthermore, all subjects
      underwent a complete molecular study of the alpha and beta globin genes by means
      of the ARMS, SSCP, DGGE, PCR and Southern blotting techniques. RESULTS: 1) The 
      101 C-->T mutation of the promoter of the beta globin gene shows a normal
      hematological picture with the Hb A2 level often slightly raised and the
      alpha/beta globin synthesis ratio slightly greater than 1; 2) beta + thalassemia
      resulting from the IVS II 844 C-->G mutation has a phenotype that is even closer
      to normal; 3) -alpha 3.7 deletion type I usually has a totally silent phenotype;
      4) the alpha Ncol mutation almost always gives rise to a sub-silent phenotype if
      it is located on gene alpha 2 and to a silent phenotype if it is found on gene
      alpha 1; 5) alpha + thalassemia due to the alpha 2 Hphl mutation displays a sub
      silent phenotype in some cases and a silent one in others; 6) triplication of the
      alpha genes gives rise to a phenotype that is quite similar to that of the -101 C
      ->T mutation of the promoter of the beta globin gene, namely one that is very
      often silent. INTERPRETATION AND CONCLUSIONS: Many of these silent varieties
      (beta + thalassemia due to the -101 C-->T mutation; alpha + thalassemia from a
      deletion or point mutation of an alpha gene; alpha alpha alpha triplication) are
      quite frequent in the overall group of thalassemias. It is therefore important
      for the operators in the field of thalassemia diagnosis to possess exact
      knowledge of them especially in order to prevent thalassemia major.

PMID- 9234572
TI  - Significance of cell proliferation index in assessing histological prognostic
      categories in Hodgkin's disease. An immunohistochemical study with Ki67 and MIB-1
      monoclonal antibodies.
AB  - BACKGROUND AND OBJECTIVE: In their review of the Rye histopathological
      classification of Hodgkin's disease, Bennett and coworkers have proposed that the
      nodular sclerosis (NS) type should be divided into two diagnostic categories on
      the basis of their clinical behaviour. In order to evaluate whether the
      proliferative activity of HD cells might correlate with histology in NS subtypes,
      we reviewed and re-evaluated cryostat and paraffin-embedded sections from 80
      cases sent to our centre from 1986 to 1991. METHODS: In the present study, we
      investigated the growth cell fraction of 53 cases of Hodgkin's disease with
      nodular sclerosis by using Ki67 and MIB1 monoclonal antibodies to determine
      whether proliferative activity is associated with different pathological subtypes
      and prognostic categories. Eight cases with an interfollicular pattern and 19
      with mixed cellularity were also investigated. The results in each group were
      compared to the others. RESULTS: The values of Ki67 and MIB1 were highly
      correlated (r = 0.88). In Hodgkin's disease with nodular sclerosis, two groups
      with significantly different growth fractions were morphologically identified:
      one with lymphocyte predominance and mixed cellularity subtypes, another composed
      of cases with variously extensive lymphocyte depletion. The figures were compared
      with those of interfollicular subtype, which fell into the first group, and of
      mixed cellularity type, in which the proliferative cell activity was
      significantly higher than in the second nodular sclerosis group. In all cases,
      Reed-Sternberg and Hodgkin cells accounted for the majority of the cell growth
      fraction, although a variable percentage of T-lymphocytes were also Ki67- or MIB1
      positive. Taking the median value (15%) of MIB1 positive cells as a cut-off, a
      significant correlation (p = 0.05) was observed between MIB1 positivity and bulky
      disease, and a good trend (but not a significant relationship) between MIB1 and
      overall survival, disease-free survival, staging and the clinical response to
      therapy. INTERPRETATION AND CONCLUSIONS: Assessment of the growth cell fraction
      in Hodgkin's disease with different nodular sclerosis patterns provides
      biological support for the morphological reclassification of their degree of
      malignancy into two main groups with different impacts on the clinical parameters
      and a possible relation with the outcome of treatment.

PMID- 9234573
TI  - Clinical and prognostic evaluation of bone marrow infiltration (biopsy versus
      aspirate) in early chronic lymphocytic leukemia. A single center study.
AB  - BACKGROUND AND OBJECTIVE: Recently published studies dealing with chronic
      lymphocytic leukemia (CLL) patients in early clinical stage reported that bone
      marrow (BM) biopsies and aspirates can be considered complementary methods of
      evaluating the extent of BM involvement. Consequently, we designed the present
      study to investigate the clinical and prognostic implications of BM biopsies and
      aspirates in a series of stage A CLL patients followed-up in a single center.
      PATIENTS AND METHODS: BM biopsy sections and aspirate smears obtained at the time
      of diagnosis from 102 CLL stage A patients were retrospectively evaluated.
      Results were correlated with clinical and hematological features as well as with
      survival and disease-progression risk. RESULTS: Diffuse (D) BM histology was
      detected in 10 patients (9.8%) while 21 (20.5%) displayed lymphocyte infiltration
      (LI) > 80%. Twenty-six patients (25.4%) died with a 5- and 10-year survival
      probability of 85% and 50%, respectively. The survival of patients with D-BM
      histology was significantly shorter than that of patients with non-diffuse (non
      D) histology (p < 0.05). Interestingly, when considering only CLL-related deaths
      (i.e. leukemia progression, infections) were considered, there was an increase in
      the statistical significance of BM histology (p = 0.01). There was no difference
      in life expectancy in cases with LI either using different cut-off levels (i.e.
      70% and 80%) or excluding non-CLL related deaths. According to our experience,
      disease progression could only be predicted by BM histology (p = 0.008), while LI
      was not useful for forecasting progression to more advanced stages (p = NS).
      INTERPRETATION AND CONCLUSIONS: In patients with early CLL, BM histology provides
      more reliable information regarding the clinical outcome of the disease than LI.

PMID- 9234574
TI  - Use of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination
      with hydroxyurea as post-transplant therapy in chronic myelogenous leukemia
      patients autografted with unmanipulated hematopoietic cells.
AB  - BACKGROUND AND OBJECTIVE: Allogeneic bone marrow transplantation remains the only
      potentially curative treatment for CML, but more than 70% of patients will be
      ineligible for allogeneic marrow transplant either because they do not have a
      suitable HLA-matched related or unrelated donor or because they are more than 50
      years old. Several experimental and clinical findings support a role for
      autologous stem cell transplantation (ASCT) in CML. It has been suggested that in
      the early phase following autografting the Ph-negative clone has a proliferative
      advantage over the Ph-positive clone. We hypothesized that post-transplant GM-CSF
      administration could reactivate the functional activity of quiescent normal
      progenitors and prolong the duration of the post-transplant proliferative
      advantage of Ph-negative over Ph-positive progenitors. In order to evaluate the
      effect of post-transplant GM-CSF administration, a pilot clinical study was
      performed in which CML patients resistant to IFN-alpha therapy were autografted
      with unmanipulated marrow or blood cells and given prolonged GM-CSF therapy post
      transplant. METHODS: Five adult CML patients conditioned with the BAVC regimen
      were reinfused with either marrow (n = 2) or blood (n = 3) cells and given
      granulocyte-macrophage colony-stimulating factor (GM-CSF). Recombinant GM-CSF was
      initially administered at standard dosage (5 micrograms/kg/day) until a white
      blood cell count > or = 2 x 10(9)/L was achieved on two consecutive examinations,
      and thereafter at a low dose (1 microgram/kg/day) for 5 to 9 months. On a weekly
      basis, GM-CSF was discontinued and hydroxyurea (1,000 mg/d) was given for two
      days. RESULTS: Evidence of trilineage engraftment was observed in all cases. At
      autografting, 3 out of the 5 patients revealed 8-9% Ph-negative metaphases.
      During the initial phase of hematopoietic regeneration, direct cytogenetic
      analysis revealed 81% and 100% Ph-negative metaphases in two cases; nonleukemic
      hematopoiesis progressively decreased and was no longer detectable at +9 months.
      One patient showed cyclic Ph-negative hematopoiesis that appeared 3 months
      following autografting and peaked at +4 and +8 months. The fourth patient showed
      a low percentage (20%) of Ph-negative metaphases 1 month after ASCT, followed by
      a significant expansion of nonleukemic hematopoiesis, which could be detected up
      to month +13. No evidence of Ph-negative hematopoiesis could be detected in one
      patient. Three patients are in chronic phase 28, 30 and 31 months after
      autografting, respectively, and two patients evolved into blast crisis.
      INTERPRETATION AND CONCLUSIONS: This pilot study demonstrates that combined GM
      CSF and hydroxyurea therapy seems to be effective in inducing and/or prolonging a
      transient period of Ph-negative hematopoiesis. The late appearance of Ph-negative
      hematopoiesis detected in two patients suggests an antileukemic activity of the
      combined GM-CSF/hydroxyurea therapy rather than an antileukemic effect of the
      conditioning regimen.

PMID- 9234575
TI  - Risk of reactivation of a recent invasive fungal infection in patients with
      hematological malignancies undergoing further intensive chemo-radiotherapy. A
      single-center experience and review of the literature.
AB  - BACKGROUND: Patients with hematologic malignancies and a history of an invasive
      fungal infection are considered to be at high risk of suffering reactivation of
      the infection during subsequent intensive chemotherapy. PATIENTS AND METHODS:
      From January 1993 to September 1996, nine patients with a hematologic malignancy
      and previous invasive pulmonary aspergillosis (IPA) or Pseudallescheria boydii
      pneumonia and five with invasive candidiasis received further intensive
      chemotherapy (n = 3) or a bone marrow or peripheral blood stem cell transplant (n
      = 11) four days to 13 months (median three months) from the start of therapy for
      the fungal infection. Five patients with IPA and all five with invasive
      candidiasis showed complete or good partial radiologic resolution of the
      infection with the primary antifungal therapy given, which was continued before,
      during and after the period(s) of subsequent neutropenia. RESULTS: Twelve of the
      14 patients showed no signs of progression or reactivation of the fungal
      infection during therapy, while two patients with active IPA died with
      progressive aspergillosis shortly after an allogeneic transplant. A review of the
      literature revealed that in both types of infections the risk of reactivation and
      dissemination appears low after achieving clinical and radiologic signs of
      response, which takes several weeks or months before proceeding to further
      antileukemic therapy. INTERPRETATION AND CONCLUSIONS: Despite lack of definite
      evidence, administration of an active antifungal drug before, during and after
      the period of neutropenia appears to be useful. In IPA, residual masses, nodules
      or cavities in the lung usually contain viable invasive fungal elements and
      should be resected whenever possible. On the other hand, the risk of reactivation
      and progression of an active fungal infection during intensive chemoradiotherapy
      is very high, and novel therapeutic strategies appear warranted in this setting.

PMID- 9234576
TI  - Primary intestinal lymphoma: clinical and therapeutic features of 32 patients.
AB  - BACKGROUND AND OBJECTIVE: Lymphomas of the gastrointestinal tract are the most
      common type of primary extranodal lymphomas, accounting for 5 to 10% of all non
      Hodgkin's lymphomas. In particular, primary intestinal lymphomas represent about
      15-20% of gastrointestinal lymphomas. New multimodal therapeutic approaches have
      improved the prognosis of this once deadly disease: we report a retrospective
      analysis of our experience with 32 cases of primary western intestinal lymphomas,
      presenting clinical, therapeutical and prognostic data. PATIENTS AND METHODS:
      From March 1989 to November 1995, 32 patients with untreated primary western
      intestinal lymphomas were submitted to radical surgery plus polychemotherapy
      (early stages, I and II; 22 patients), or polychemotherapy alone (advanced stage,
      III and IV; 10 patients). The most frequent symptoms were abdominal pain, nausea,
      vomiting and weight loss. The tumor was located in the jejunum in 2 cases (6.2%),
      in the proximal small bowel in 15 cases (46.9%), in the distal and terminal ileum
      in 8 cases (25%), in the colon and rectum in 4 cases (12.5%), and multiple sites
      were found in 3 cases (9.4%). According to histology, 26 patients had high-grade
      and 6 low-grade non-Hodgkin's lymphoma. RESULTS: Stage I-II patients underwent
      radical resection of the tumor and chemotherapy; advanced (III-IV) stage patients
      were treated with chemotherapy alone as first-line approach. Of the 32 patients,
      24 (75%) achieved a complete response (CR); according to stage, all stage I-II
      patients had CR, while only 2 of the 10 stage III-IV patients reached CR. The
      risk of a lower response rate was significantly correlated with the presence of
      advanced stage (III-IV) (p = 0.000001). The overall 5-year survival rate was 59%,
      with a relapse-free survival rate of 72% among the 24 complete responders.
      INTERPRETATION AND CONCLUSIONS: Intestinal lymphomas differ significantly from
      their gastric counterpart, not only in pathology, but also with regard to
      clinical features, management and prognosis. Our experience confirm the efficacy
      of the surgery-chemotherapy combination in obtaining a good remission rate for
      localized early primary intestinal lymphoma and indicates that this combination
      represents the only means for managing complications.

PMID- 9234577
TI  - Idarubicin in patients with diffuse large cell lymphomas: a randomized trial
      comparing VACOP-B (A = doxorubicin) vs VICOP-B (I = idarubicin).
AB  - BACKGROUND AND OBJECTIVE: Idarubicin is an effective drug in acute leukemia but
      its use in non-Hodgkin lymphomas (NHLs) is not yet well established. We evaluated
      its efficacy in patients with diffuse large cell lymphoma (DLCL) by means of a
      randomized trial comparing two 12-week regimens (VACOP-B and VICOP-B) which
      differed only in the anthracycline drug used (doxorubicin vs idarubicin).
      METHODS: From January 1992 to December 1994, 104 patients aged less than 65 years
      with de novo advanced stage DLCL were enrolled. Fifty-two patients were treated
      with VACOP-B (doxorubicin 50 mg/sqm) and 52 with VICOP-B (idarubicin initially 8
      mg/sqm and thereafter 10 mg/sqm). RESULTS: Clinical characteristics of the two
      groups were not significantly different. One HBsAg+ patient died of hepatic
      necrosis in the VICOP-B arm, and severe (WHO grade > 2) toxicities occurred in 7
      patients treated with VACOP-B and in 5 treated with VICOP-B; the only significant
      difference was for mucositis (p = 0.02). Complete remission (CR) was obtained in
      79% of patients receiving VACOP-B and in 56% (idarubicin 8 mg/sqm) and 75%
      (idarubicin 10 mg/sqm) of those in the VICOP-B group (p = n.s.). Prognostic
      factors that negatively affected CR were advanced stage in VACOP, bone marrow
      infiltration in both schedules. At a median follow-up of two years, overall
      survival (67% VACOP and 61% VICOP) and disease-free survival (65% and 67%,
      respectively) were not significantly different. INTERPRETATION AND CONCLUSIONS:
      Idarubicin is slightly less toxic than doxorubicin; at a dose of 10 mg/sqm the
      former is easily tolerated and shows the same efficacy as doxorubicin in the
      treatment of DLCL.

PMID- 9234578
TI  - Hepatitis C virus infection among cryoglobulinemic and non-cryoglobulinemic B
      cell non-Hodgkin's lymphomas.
AB  - BACKGROUND AND OBJECTIVE: Since hepatitis C virus (HCV) infection has been
      associated with different histotypes of B-cell non-Hodgkin's lymphoma (NHL), with
      or without concomitant production of cryoglobulins (cryolg), we have investigated
      the prevalence of the infection among NHL with the aim of defining its
      relationship with the histotype and with the production of cryolg. METHODS: Four
      hundred and seventy unselected, consecutive patients with a diagnosis of B-cell
      NHL were investigated. Anti-HCV antibodies (Ab) and cryolg were sought in all
      while HCV RNA and rheumatoid factor were detected on HCV-Ab positive samples.
      RESULTS: Overall, the prevalence of HCV infection was 8.9% (42/470). It was 95.4%
      (#21) among the 22 patients with, and 4.6% (#21) among the 448 without production
      of cryoIg. The most common histotype among the HCV-positive, cryoIg-producing
      cases, was the immunocytoma (16/21, 76%). Among the HCV-positive, non cryoIg
      producing cases, the marginal zone and the follicle center lymphomas were the
      commonest. INTERPRETATION AND CONCLUSIONS: Close association between HCV
      infection and cryoIg production, already described in mixed cryoglobulinemia, is
      confirmed also among B-cell NHL. Nevertheless, 50% of HCV-related lymphomas are
      non-cryoIg producers. Low-grade lymphomas (in particular the immunocytoma) are
      the most frequent HCV-related lymphomas. Since new therapeutic strategies might
      be necessary if the virus is detected, screening for cryoIg and for HCV-Ab among
      B-cell NHL at diagnosis is mandatory.

PMID- 9234579
TI  - Relationship of blood transfusion, post-operative infections and immunoreactivity
      in patients undergoing surgery for gastrointestinal cancer.
AB  - BACKGROUND AND OBJECTIVE: The immunosuppression induced by perioperative blood
      transfusion (BT) and its effect on the incidence of post-surgical infectious
      complications remains controversial. In this study, the relationship between BT
      and postoperative infections was investigated in 136 gastrointestinal cancer
      patients submitted to curative surgery. METHODS: Clinical and laboratory
      variables, data on postoperative infections, infection risk factors and types of
      transfusion were analyzed. Immune function was evaluated in 76 patients and
      compared before and after surgery. RESULTS: The overall postoperative infection
      rate was 28% for the transfused and 4.6% for the untransfused patients. The
      univariate analysis of investigated variables indicated that BT, progressive
      cancer stage, duration of surgery, drains, all had significant association with
      infection. The multiple logistic regression analysis confirmed BT (p = 0.0028)
      and advanced cancer stage (p < 0.001) as significant risk factors for the
      postoperative infections. The results of immunological tests showed no
      significant differences between transfused and untransfused patient groups, after
      surgery. Comparing pre- and postoperative data from individual patients, an
      impairment of natural killer (NK) activity was observed in all patients
      regardless of their transfusional status; the synthesis of interleukin-2 (IL-2)
      and interferon-gamma (IFN-gamma) was also decreased respectively in the
      untransfused and in the transfused patients. INTERPRETATION AND CONCLUSIONS:
      These results indicate that other factors, beside BT, can induce
      immunosuppressive effects in these patients and thus increase their
      susceptibility to postoperative infections.

PMID- 9234580
TI  - Verification and comparison of two different predictive equations in Hodgkin's
      disease.
AB  - BACKGROUND AND OBJECTIVE: In recent years, two predictive equations to estimate
      median expected survival at diagnosis for patients affected with Hodgkin's
      disease have been developed at the University of Pavia Medical School. The
      present retrospective work was aimed at testing correlation between mean survival
      estimated using the two equations and observed survival, and at comparing the
      results of the two different equations. METHODS: Fifty-three deceased patients
      were considered from a series of 114 consecutive ones. All these patients had
      been treated in a conventional way according to therapeutic modalities similar to
      those used in the series from which the two equations were derived. Expected
      median survival values calculated with the older, linear equation and with the
      newer exponential one were compared with observed survival. RESULTS: Mean
      survival of the whole series was over 24 years, with survival probabilities of
      85% after 5 years and 74% after 10 years. Using the first predictive equation on
      the 53 deceased patients resulted in a satisfactory correlation between estimated
      median survival and real survival: Pearson's R correlation coefficient value is
      0.5996, with a t value of 5.35 and p < 0.001. The more recent exponential
      predictive equation showed a better correlation between estimated median survival
      and observed survival: R = 0.7338, t = 7.71, p < 0.001. INTERPRETATION AND
      CONCLUSIONS: The new exponential equation, while apparently complex, is superior
      to the older one, and is a very reliable and straightforward tool for estimating
      median expected survival: its forecast proves to be an important pretreatment
      parameter in every HD patient. These observations support widespread use of this
      tool in clinical practice to evaluate the prognosis of Hodgkin patients in a more
      accurate and flexible way.

PMID- 9234581
TI  - Noninvasive diagnosis of pulmonary embolism.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE), with an incidence of 23 per
      100,000 patients per year, is a frequent clinical problem, responsible for
      200,000 deaths each year in the United States. Pulmonary angiography, the gold
      standard for diagnosing PE, is invasive, costly and not universally available.
      Moreover, PE is confirmed in only approximately 30% of patients in whom it is
      suspected, rendering noninvasive screening tests necessary. Several strategies
      have been recently proposed to reduce the need for pulmonary angiography in the
      diagnostic workup of pulmonary embolism. The objective of this article is to
      analyze the individual performance of the new diagnostic instruments and their
      combination in rational diagnostic strategies. METHODS: The author has been
      working in this field and has contributed original papers on diagnosis of
      pulmonary embolism and cost-effectiveness of noninvasive diagnostic tests. In
      addition, the material examined in this article includes articles published in
      the journals covered by the Science Citation Index and Medline. RESULTS: Several
      strategies have been recently proposed to reduce the need for pulmonary
      angiography in the diagnostic workup of pulmonary embolism. The PIOPED study has
      established the value of ventilation-perfusion lung scan, a normal perfusion lung
      scan virtually ruling out PE, whereas a high probability lung scan is considered
      diagnostic in face of reasonable clinical suspicion. All other lung scan results
      are nondiagnostic. However, clinical evaluation, although insufficiently accurate
      to yield a definitive diagnosis, is probably reliable enough to be used for
      estimating pretest probability of PE. The combination of a low clinical
      probability of PE and a so-called low probability lung scan yields a very low
      posttest probability of PE, thus foregoing the need for pulmonary angiography.
      Other useful instrument in patients with nondiagnostic scans is plasma D-dimer
      (DD) measurement (ELISA assay), which when under a cutoff value of 500
      micrograms/L potentially exclude PE, due to high sensitivity (97%). Conversely,
      venous compression ultrasonography of the lower limbs (US) is highly specific
      (98%) for deep vein thrombosis (DVT), and disclosing a DVT warrants anticoagulant
      treatment without resorting to angiography. The potential role of
      echocardiography is also discussed. The rational sequence of noninvasive tests is
      currently under discussion. Performing D-dimer and US before lung scan may be the
      most cost-effective strategy, pulmonary angiography being performed only in case
      of an inconclusive noninvasive workup. INTERPRETATION AND CONCLUSIONS: Even
      though PE remains a difficult diagnostic challenge, the availability of novel
      noninvasive tests (plasma D-dimer and ultrasonography of the lower limbs) and the
      rehabilitation of clinical assessment allow a more rational and sparse
      prescription of pulmonary angiography. More work needs to be done to assess test
      performances and refine diagnostic strategies in distinct patient subgroups,
      particularly those hospitalized. Screening patients with plasma D-dimer and
      ultrasonography of the lower limbs may be the most cost-effective strategy, at
      least in outpatients.

PMID- 9234582
TI  - Apparently normal ankyrin content in unsplenectomized hereditary spherocytosis
      patients with the inactivation of one ankyrin (ANK1) allele.
AB  - The study of erythrocyte membrane protein concentration by polyacrylamide gel
      electrophoresis (PAGE) is the first step in approaching the primary molecular
      defect in hereditary spherocytosis (HS). Normal or greater than normal protein
      2.1 levels were found in ten unrelated HS patients showing the inactivation of
      one ankyrin allele. Erythrocyte membranes from the same patients, once
      splenectomized, showed a homogeneous degree of protein 2.1 reduction. Thus
      protein 2.1 levels could misleadingly appear normal due to the high number of
      circulating reticulocytes. To calculate the true ankyrin level using PAGE and
      consequently to avoid mistakes in studying a mutated gene, a simple equation,
      based on the number of reticulocytes, was developed.

PMID- 9234583
TI  - Differences in phycoerythrin- or fluorescein-isothiocyanate conjugated 8G12 on
      CD34+ cell evaluation.
AB  - To evaluate the equivalence of 8G12 conjugated with either phycoerythrin (PE) or
      fluorescein isothiocyanate (FITC), duplicate fluorochrome-8G12 labelling was
      carried out in 229 samples. Additionally, 53 samples were simultaneously
      immunostained with FITC-8G12 and PE-8G12. Significantly higher values (p < 0.001)
      were observed in PE-CD34+ cells when compared with FITC-CD34+ cells both in
      duplicate and simultaneous analysis. Our data suggest that the choice of
      fluorochrome is relevant in the measurement of CD34+ cells with 8G12.

PMID- 9234584
TI  - Duplication of the der(13)t(12;13)(p13;q14) in chronic myelomonocytic leukemia.
AB  - A case of chronic myelomonocytic leukemia with a reciprocal translocation
      (12;13)(p13;q14) and other numerical and structural abnormalities is described.
      Most of the metaphases examined showed duplication of the der(13)t(12;13),
      leading to trisomy of the translocated segment of chromosome 12. Using
      fluorescence in situ hybridization we observed that the breakpoint on chromosome
      13 is centromeric to the retinoblastoma gene. Since other cases with apparently
      similar t(12;13) have recently been reported, we conclude that this structural
      rearrangement may be a rare but non random event in hematologic disorders.

PMID- 9234585
TI  - The expression of proliferation and quiescence associated antigens in acute
      myeloid leukemia correlates with survival duration: analysis of 15 refractory
      cases.
AB  - In this study, blast cells from 15 patients with acute myeloid leukemia resistant
      to induction therapy were examined with two monoclonal antibodies that identify,
      respectively, the nuclear protein specifically expressed in non proliferating
      cells (statin) and the proliferating cell nuclear antigen (PCNA). We found that
      statin values varied widely, ranging from 0.6% to 14.7% (mean value 6.4%). When
      the patients were subdivided according to the mean value, those presenting with
      higher statin values survived for a shorter period of time than the ones
      characterized by lower levels (p = 0.003). We observed a wide variation in the
      range of PCNA values; however, if an agreement between survival duration and at
      least one of the proposed markers was considered, all but one case displayed
      concordance between survival duration and PCNA and/or statin values (in addition,
      4/15 cases showed agreement for both markers). These preliminary data could
      indicate a possible discriminating prognostic factor between categories of
      patients characterized by different aspects of resistance, perhaps susceptible to
      different salvage therapy approaches.

PMID- 9234586
TI  - Gestational thrombocytopenia: a prospective study.
AB  - Gestational thrombocytopenia (GT) is commonly observed in pregnancies with
      otherwise limited obstetric and hematologic complications. However, few data are
      available on the natural history of the disease, and on the recurrence of
      thrombocytopenia in subsequent pregnancies. From June 1987 to December 1993, 37
      consecutive patients with GT were enrolled in a prospective study, with a total
      of 41 pregnancies observed. Vaginal delivery was carried out in 33/41 (80%); two
      patients were transfused fused with packed red cells for obstetric hemorrhage
      (post-partum uterine atony). Neonatal bleeding did not occur. In all newborns
      platelet count was performed within 24 hours after delivery: 2 newborns had mild
      (80 and 75 x 10(9)/L) and 1 severe thrombocytopenia (12 x 10(9)/L) at birth; all
      of them recovered to a normal platelet count within 10 days without treatment.
      Twenty-eight out of 3% patients were followed for 12 months after delivery; in 23
      a normalization of platelet count occurred within 1-5 months from delivery; in 5
      mild thrombocytopenia (100-120 x 10(9)/L) persisted during follow-up. Four
      patients had a second pregnancy and recurrence of thrombocytopenia was observed
      in all of them. GT is rarely associated with bleeding episodes during pregnancy
      and partum, and recovers spontaneously within few months after delivery but
      thrombocytopenia can recur in subsequent pregnancies. Severe thrombocytopenia is
      not observed in newborns so that a conservative management is warranted.

PMID- 9234587
TI  - Plasma homocysteine levels in 10 patients with polycythemia.
AB  - Polycythemia and hyperhomocysteinemia are risk factors for thrombosis. Since red
      blood cells actively metabolize methionine to homocysteine, we investigated
      whether or not patients with polycythemia have increased plasma levels of
      homocysteine, which might contribute to their increased thrombotic risk. In ten
      patients with polycythemia, the plasma homocysteine levels were measured before
      phlebotomy, three days after the procedure and 1-2 months later. The baseline
      mean plasma homocysteine levels in patients (9.7 +/- 1.6 mumol/L [+/-SD]) did not
      differ significantly from that found in 30 sex- and age-matched healthy controls
      (12.2 +/- 6.9). Despite a fall in the patients' mean [+/-SD] hematocrit from 0.50
      +/- 0.02 at baseline to 0.47 +/- 0.03 three days after phlebotomy (significant at
      95%) and to 0.48 +/- 0.02 after 1 to 2 months (not significant), the mean plasma
      homocysteine levels did not change significantly (9.9 +/- 2.3 mumol/L at 3 days
      and 9.7 +/- 2.1 mumol/L at 1-2 months). It is unlikely that high plasma
      homocysteine levels contribute to the increased thrombotic risk of polycythemic
      patients.

PMID- 9234588
TI  - Severe bleeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome.
      Case report and review of literature.
AB  - A 17-year-old girl was admitted to our department with a hemorrhagic syndrome due
      to a serious coagulopathy; prothrombin time (PT) INR was 2.46 and the activated
      partial thromboplastin time (aPTT) ratio 3.46. Coagulation tests with pooled
      normal fresh plasma did not correct aPTT because of a coagulation inhibitor, and
      only partially corrected PT. Factor II activity reached only 5%. Diluted Russell
      viper venom tests (dRVVT) and kaolin clotting time (KCT) of patient plasma (PP)
      and of a mixture of PP/normal plasma (NP) detected the lupus anticoagulant (LA).
      The level of factor II antigen was 10%. We diagnosed systemic lupus erythematosus
      (SLE) with a rare acquired hypoprothrombinemia-LA syndrome (HLAS). The patient
      was treated with corticosteroids and high-dose Ig and a normal PT value was re
      established.

PMID- 9234589
TI  - Response to sequential treatment with lymphoblastoid interferon-alpha in patients
      with Ph+ chronic myeloid leukemia unresponsive to recombinant interferon-alpha
      (rIFN alpha 2a) and neutralizing-rIFN alpha 2a antibodies negative.
AB  - Nine Ph+ CML patients in chronic phase who were hematologically and/or
      karyotypically unresponsive to recombinant-IFN alpha 2a (rIFN alpha 2a) and
      neutralizing-rIFN alpha 2a Abs negative were shifted from rIFN alpha 2a to
      lymphoblastoid-IFN alpha (IFN alpha-Ly) therapy. After 3 months of IFNa-Ly
      treatment, the hematologic response was reinduced in 3 out of the 6 pts who were
      resistant to previous rIFN alpha 2a therapy, and was maintained in 2 out of 3
      patients who were hematologically but not karyotypically responsive to rIFN alpha
      2a. After 6 and 12 months, the hematologic response was progressively lost, being
      present only in 3 out of 7 and in 2 out of 3 evaluable patients respectively.
      None of the hematologically responsive patients achieved a karyotypic response
      (Ph neg. metaphases-0%). One patient, who was hematologically responsive,
      continued being treated with IFN alpha-ly for 36 months but he did not achieve
      any karyotypic response. The results of this study suggest that in the
      unresponsive and neutralizing-rIFN alpha 2a Abs negative CML patients a change in
      therapy, by using a non cross-reactive type of IFN alpha, would not be
      advantageous.

PMID- 9234591
TI  - All-trans retinoic acid in combination with alpha-interferon and dexamethasone
      for advanced multiple myeloma.
AB  - The in vitro inhibitory effect of all-trans retinoic acid (ATRA) on myeloma cell
      growth may be synergistically potentiated by the activity of dexamethasone (DEX)
      and alpha-interferon (IFN). We treated 10 patients with advanced, refractory
      multiple myeloma (MM) using a combination of ATRA (100 mg p.o., once a day for
      two weeks every month), DEX (40 mg i.v., for 4 days every 4 weeks) and IFN (3 MU
      s.c., three times a week). Eight patients completed at least three months of
      treatment and were evaluable for response. Two of them showed a partial response
      which persists after 15 to 17 months. Three patients experienced a stable plateau
      phase of 4 to +11 months, with a significant improvement in the performance
      status and bone pain. Progressive disease was seen in the remaining three
      patients. We conclude that the association of ATRA, DEX and IFN warrants further
      consideration in MM patients.

PMID- 9234590
TI  - The association of cyclophosphamide and dexamethasone in advanced refractory
      multiple myeloma patients.
AB  - VAD is the most active regimen in refractory myeloma patients; however, the role
      of vincristine and doxorubicin remains unclear. Relatively high doses of
      cyclophosphamide (3.6 g/sqm) increased the response rate and survival in
      resistant MM. Cyclophosphamide and dexamethasone were administered to 28 patients
      with advanced refractory myeloma. Thirteen patients received cyclophosphamide 1.2
      g/sqm on days 1 and 3 and dexamethasone 40 mg/day from day 1 to day 4, every 4
      weeks for 6 cycles (schedule A); 15 patients were treated with cyclophosphamide
      0.5 g/sqm on days 1 and 3 and dexamethasone 40 mg/day from day 1 to day 4, every
      two weeks for 12 cycles (schedule B). Overall, 21 patients (75%) responded and 10
      achieved an objective response (36%), while 11 reached a partial response. Twenty
      patients died (68%), most of them of disease progression, and 8 are still alive
      (32%). Median length of response and survival is 6 and 8 months, respectively.
      Therapy was easily applied and well tolerated. The overall response rate (75%)
      compares favorably with the best published results in this setting. The two
      schedules proved to be equally effective but patients treated with schedule B had
      more infections, which may have been related to the higher dosage of steroids.

PMID- 9234592
TI  - Lysis of a right atrial thrombus of more than a week's duration by high dose
      urokinase in a one-year-old child.
AB  - The case of a one-year-old child in whom a large catheter-related right atrial
      thrombus of more than a week's duration was dissolved by urokinase is presented.
      After one week of unsuccessful heparin treatment, urokinase, via a central venous
      catheter, was added at a dose of 1500 IU/kg/h. Urokinase was subsequently
      increased by 1000 U/kg/h every day up to a maximum of 4500 IU/kg/h on the basis
      of thrombus size reduction as assessed by daily cross-sectional echocardiography.
      One week later the thrombus was almost completely dissolved. No major bleeding
      occurred. Warfarin was given for the next three months and the international
      normalized ratio (INR) was maintanied between 2 and 3. At the end of warfarin
      treatment echocardiography was negative for right atrial thrombosis. This case
      suggests that local high dose urokinase therapy can be safely and successfully
      used to dissolve large right atrial thromboses of more than a week's duration.

PMID- 9234593
TI  - Pretransplant factor XII levels correlate with prognosis in patients undergoing
      autologous graft for hematological malignancies.
AB  - A retrospective analysis of data collected in a previous study suggested that pre
      conditioning levels of factor XII might have prognostic value in autologous graft
      recipients. In order to confirm whether pre-transplant factor XII (pFXII) levels
      could be correlated with outcome, seventy-six (35 autologous and 41 allogeneic)
      transplant recipients were prospectively evaluated. A significant direct
      relationship was found between pFXII levels and both overall and disease-free
      survival in the autologous grafts, but not in the allogeneic ones. Although the
      molecular mechanisms of this relationship still need to be clarified, these data
      seem to justify larger efforts to confirm whether factor XII (FXII) assay should
      be used in pre-transplant evaluation of patients.

PMID- 9234594
TI  - Granulocyte colony-stimulating factor-primed leukocyte transfusions in candida
      tropicalis fungemia in neutropenic patients.
AB  - Optimal management of fungemia in neutropenic patients is still controversial.
      Several reports have already stressed the poor prognosis in invasive candidiasis
      (80% mortality in several reports). Therefore granulocyte transfusions would
      appear to be useful in the management of these infections. We report the use of
      rhG-CSF-primed granulocyte transfusions plus amphotericin B in two neutropenic
      patients who developed life-threatening systemic fungal infections. This approach
      was successful and both patients fully recovered from the infection.

PMID- 9234595
TI  - The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and
      lymphoid leukemias.
AB  - BACKGROUND AND OBJECTIVE: The AML1 gene was identified in 1991 by cloning the
      t(8;21) chromosome translocation associated with FAB M2 acute myeloid leukemia
      (AML). AML1 encodes a nuclear transcription factor (TF) which shows homology in
      its 5' part with the Drosophila melanogaster segmentation gene, runt, and
      contains a transactivation domain in the carboxyterminal portion. In the t(8;21),
      AML1 is fused to the ETO (MTG8) gene, resulting in a hybrid AML1/ETO mRNA, which
      in turn is translated into a chimeric protein. The objective of this article is
      to review here the main structural and biological features of AML1 and of its
      fusion products, with special focus on their clinical correlations and their
      potential usefulness for prognostic and monitoring studies in human leukemia.
      EVIDENCE AND INFORMATION SOURCES: The material examined in the present review
      includes articles and abstracts published in journals covered by the Science
      Citation Index and Medline. STATE OF ART: The normal AML-1 protein forms the
      alpha-subunit of the heterodimeric TF core binding factor (or CBF), whose beta
      subunit is encoded by the CBF beta gene on chromosome 16q22. CBF beta is
      rearranged and fused to the MYH11 gene in the AML M4Eo-associated inv(16)
      aberration. Thus, the two most common chromosome abnormalities of AML, i.e.
      t(8;21) and inv(16), affect the two subunits of the same target protein. This
      suggests that the wild type CBF must exert an important role in the control of
      myeloid cell growth and/or differentiation. Evidence that AML1 is a pivotal
      regulator of definitive hematopoiesis has been recently provided by analyzing
      AML1 knockout mice. The chromosome region 21q22, where AML1 maps, is involved in
      several other karyotypic aberrations, such as the t(3;21) translocation
      associated with a subset of therapy-related myelodysplastic syndromes and AML,
      and the blast phase of chronic myelogenous leukemia. In this abnormality, three
      distinct genes: EVI1, EAP, MDS1, located on chromosome band 3q26, have been
      identified that may recombine with AML1. Finally, the recently cloned t(12;21)
      translocation has been found to involve the TEL gene (coding for a novel TF) on
      12p13, and AML1 on 21q22. This alteration, which results in the production of a
      TEL/AML1 chimeric protein, is restricted to pediatric B-lineage acute lymphoid
      leukemia (ALL), where it represents the most frequent molecular defect known to
      date (up to 25% of cases). Strikingly, the same t(12;21) is identified in only
      0.05% of pediatric B-lineage ALL cases analyzed by conventional karyotyping.
      Other relevant characteristics of TEL/AML1-positive ALL are frequent deletion of
      the other TEL allele and association with an excellent prognostic outcome.
      PERSPECTIVES: It is expected that future studies will provide more detailed
      information on the leukemogenic effect of AML1 alterations, and better define the
      prognostic relevance of detecting the hybrid proteins formed by this gene at
      diagnosis and during remission.

PMID- 9234596
TI  - Lung mechanics and gas exchange in pulmonary embolism.

PMID- 9234597
TI  - Anemia of chronic disorders in systemic autoimmune diseases.
AB  - BACKGROUND AND OBJECTIVE: Anemia of chronic disorders (ACD) is a mild to moderate
      anemia characterized by decreased serum iron, decreased total iron-binding
      capacity and increased iron stores that occurs in a wide variety of diseases
      including cancer, chronic infections and inflammatory disorders. The reason for
      this review is two-fold. First, systemic autoimmune diseases are frequently
      characterized by ACD. Second, advances in our knowledge of the pathophysiology of
      systemic autoimmune diseases as well as pathogenesis and treatment of ACD have so
      far been dealt with separately. Consequently, the approach to the evaluation of
      ACD in systemic autoimmune disorders has usually been either immunology- or
      hematology-oriented. The aim of this review is to integrate the pertinent
      information from both these fields in order to arrive at a more complete
      understanding of a problem common to hematologists and immunologists. INFORMATION
      SOURCES: The articles reviewed have been published in journals listed in the
      Science Citation Index and Medline. In addition, the authors have a vast
      experience in the field of hematology and are actively working in the field of
      systemic autoimmune disorders. STATE OF ART AND PERSPECTIVES: ACD is a parameter
      of disease activity in systemic autoimmune diseases. The severe inflammatory
      stimuli responsible for the pathophysiology of these disorders lead to several
      systemic changes (referred to as chronic active phase response) through which the
      organism tries to cope with chronic tissue injuries. These reactions are brought
      about by inflammation-associated cytokines, like IL-6, IL-1, TNF alpha, TGF beta
      that regulate hepatic synthesis of acute phase proteins. Many cytokines involved
      in chronic acute phase response, including IL-1, TNF alpha, TGF beta, have an
      inhibitory activity on erythroid colony formation in vitro. In addition,
      circulating TNF alpha is elevated in rheumatoid arthritis (RA), IL-1 beta serum
      levels are significantly increased in RA with ACD and RA patients treated in vivo
      with antibodies (Abs) to TNF alpha show disease improvement, including an
      increase in Hb values. Reduced erythropoietin (EPO) activity, usually the result
      of reduced production, plays a role in the pathogenesis of ACD observed in
      systemic autoimmune diseases. Both the production and the action of EPO may fall
      under the control of IL-1 and IFN-gamma. The most controversial and stimulating
      aspect of the pathogenesis of ACD in systemic autoimmune disorders is the role of
      iron metabolism and nitric oxide (NO), which contributes to the regulation of
      iron cellular metabolism. Both iron deficiency and iron overload may influence
      the proliferation of B and T lymphocytes and differentially affect T helper (TH)
      1 and TH-2 lymphocytes. Furthermore, TH-1 cytokines stimulate and TH-2-type
      cytokines inhibit NO production. For these reasons, cell-mediated immunity may be
      expected to have influence on NO synthesis and on the mechanisms leading to iron
      accumulation in the reticuloendothelial system.

PMID- 9234598
TI  - Association between non-Hodgkin's lymphoma and essential thrombocythemia.

PMID- 9234599
TI  - Promotion of platelet production by hTPO cDNA injection.

PMID- 9234600
TI  - Pregnancy in patients with immune thrombocytopenic purpura.

PMID- 9234601
TI  - Pronounced electrolyte abnormalities in a patient with acute leukemia.

PMID- 9234602
TI  - Spiral CT angiography in the study of the carotid stenoses.
AB  - PURPOSE: To determine sensitivity, specificity and diagnostic accuracy of spiral
      CT angiography (S-CTA) compared to Digital Subtraction Angiography (DSA).
      MATERIALS AND METHODS: We studied 40 patients with suspected cerebro-vascular
      insufficiency by carotid stenosis. Diagnostic examinations by means of S-CTA and
      DSA were carried out within 24 hours of each other. Twelve of these patients
      underwent thromboendoarterectomy (TEA). Prospeed SX GE was used for S-CTA. Post
      processing was performed using Maximum Intensity Projection (MIP) after deleting
      osteo-muscular structures and CT angiograms were displayed in an oblique anterior
      view at an angle of 10 degrees-15 degrees along the longitudinal axis. For DSA
      examinations, a Siemens Politron 1000 VR unit was used. RESULTS: In this study S
      CTA showed values of sensitivity, specificity and diagnostic accuracy of 88%,
      100% and 96%, respectively. CONCLUSIONS: In the future, with the improvement of
      non-invasive techniques (S-CTA, MRA), DSA should be replaced, as the gold
      standard, in the evaluation of stenotic disease of the carotid bifurcation.

PMID- 9234603
TI  - Dural tail in pituitary adenoma.
AB  - Although a dural tail has been described in association with meningiomas and,
      rarely, with other tumors in MR imaging with Gd-DPTA. Recently, a pituitary
      lesion was evaluated by MRI and presented a tail. For this reason the lesion was
      thought to be a meningioma of the tuberculum sellae, but at surgery proved to be
      an adenoma.

PMID- 9234604
TI  - Developmental stages of clinical research programs, Part II.

PMID- 9234605
TI  - Vaginal bleeding and abuse: assessing pregnant women in the emergency department.
AB  - PURPOSE: This study was done to determine the prevalence of physical abuse among
      an ethnically stratified group of pregnant women experiencing vaginal bleeding.
      DESIGN: The design of this study was a cross-sectional survey using two screening
      tools: the Abuse Assessment Screen (AAS) and the Danger Assessment (DA). SAMPLE:
      The study sample consisted of 261 African-American, Hispanic, and Anglo pregnant
      women seen for vaginal bleeding in private and public emergency departments in a
      large (more than 2,000,000 people) metropolitan area. METHOD: All women with
      vaginal bleeding were interviewed in a private examination room. With the help of
      an interviewer, each subject completed both screening tools and was later offered
      information about abuse as well as community resources. Each woman's pregnancy
      status was validated with either a urine pregnancy test or a serum beta human
      chorionic gonadotropin, and her discharge diagnosis was obtained from the
      emergency department record. DATA ANALYSIS: Of the 261 pregnant women
      interviewed, 87 (33.3 percent) reported abuse, that is, 26.7 percent of the
      African-American women, 25.2 percent of the Hispanic women, and 58.3 percent of
      the Anglo women. Overall, Anglo women reported significantly more abuse (X2 =
      21.96; df = 2; p < .00002) than non-Anglo women. We found no significant
      differences in reported abuse among the diagnostic groups. Abused and nonabused
      women significantly (p < .0005) differed on their DA scores (2.89 vs .55,
      respectively), but these scores were not significantly different among
      ethnicities. CONCLUSIONS: Abuse of pregnant women reporting to emergency
      departments is common and can be detected readily with a two-question, five
      minute screen. Once an abused woman is identified, a danger assessment screen can
      further identify whether she is at high risk for escalating violence in her home.

PMID- 9234606
TI  - Congenital hepatic hemangioma in the neonate.

PMID- 9234607
TI  - Tracking perinatal infection: is it safe to launder your scrubs at home?
AB  - PURPOSE: This descriptive pilot study was conducted during 1991 and 1992 to
      determine the effect of wearing home-laundered scrub clothing in labor and
      delivery on the perinatal infection rate. METHOD: Unit meetings were conducted to
      instruct the 68 participating employees to launder their scrub clothing in an
      automatic washing machine, and to dry them in an automatic dryer on a hot
      setting. Statistics, including total births and cesarean births, were gathered,
      including all cesarean births during the years of 1991 and 1992 at the two study
      sites. Infection rates were monitored by the infection control department and
      reported frequently to the infection control committee and the medical and
      nursing staff. Employees were surveyed to assess their satisfaction after
      purchasing and wearing their own scrub clothing. The method for determining the
      perinatal infection rate in this study was based on the National Nosocomial
      Infections Surveillance System, which combines exogenous and endogenous factors
      when assessing the rate of wound infections(6). The method for monitoring the
      newborn infection rate in this study was outbreak surveillance. CONCLUSIONS: Home
      laundered scrub clothing can be worn safely in labor and delivery units,
      including the operating rooms contained in those units. This practice can reduce
      costs without increasing surgical wound infection rates.

PMID- 9234608
TI  - Assessing head injuries in children.

PMID- 9234611
TI  - The hypothesis: its use and meaning.

PMID- 9234609
TI  - How does maternal employment affect preterm infants?

PMID- 9234610
TI  - Scolding, spanking, and time-out revisited.

PMID- 9234613
TI  - Cultural competence in patient education.

PMID- 9234612
TI  - Maternal vs. fetal rights.

PMID- 9234614
TI  - Nurses and pharmacists: a prescription for improved patient care.

PMID- 9234615
TI  - [A study of papillary renal cell carcinoma. Clinicopathological,
      immunohistochemical features and its typing].
AB  - BACKGROUND: Papillary renal cell carcinomas (PRCCs) are genotypically distinct
      from nonpapillary renal cell carcinomas. METHODS: We studied the clinical,
      pathomorphological, immunohistochemical features in 34 PRCCs and 7 papillary
      renal adenomas. Immunohistochemical studies were performed using lectins and
      antibodies against cytokeratins, epithelial membrane antigen and Tamm-Horsfall
      protein. RESULTS: PRCCs were divided into two types based on the features of
      tumor cells and vascular stalks. Fifteen PRCCs displayed small cuboidal cells
      with basophilic cytoplasm and thin, short vascular stalks (type 1,
      micropapillary). Nineteen PRCCs displayed large columnar cells with eosinophilic
      cytoplasm and edematous or fibrous thick stalks (type 2, macropapillary).
      Infiltration of foam cells was more common in type 1. Co-existence of papillary
      renal adenomas was recognized in three cases among type 1, but in only case among
      type 2. In type 1, a male to female predominance was evident (13:2), and the
      majority of tumors in type 1 were in lower nuclear grade and lower stage. The 5
      year survival rates of patients in type 1 and 2 were 87% and 46%, respectively.
      Immunohistochemically, 15 (100%) cases in type 1 were diffusely positive for
      cytokeratin 7 (CK7), 15 (100%) were positive for cytokeratin 19 (Progen 19) and
      11 (73%) were positive for dolichos biflorus agglutinin (DBA). In type 2, only 4
      (19%) cases focally stained for CK7, 10 (53%) were stained for Progen 19 and only
      2 (10%) were positive for DBA. The staining pattern in papillary renal adenoma
      was similar to that of type 1, all cases were positive for CK7, four of five
      cases (80%) were positive for Progen 19 and five of seven cases (71%) were
      positive for DBA. CONCLUSION: The pathomorphologic and immunohistochemical
      features suggested that it is possible to divide PRCCs into 2 types and that
      PRCCs in type 1 confer an favorable prognosis. Furthermore, our results supported
      the possibility of adenoma-carcinoma sequence.

PMID- 9234617
TI  - [Overexpression of c-erbB-2 and p53 oncoprotein in renal pelvic and ureteral
      carcinomas with reference to the expression of Ki-67 antigen as a proliferation
      marker].
AB  - PURPOSE: We determine the significance of c-erbB-2 and p53 gene in the
      progression of renal pelvic and ureteral carcinomas. METHODS: Overexpression of c
      erbB-2 and p53 oncoprotein was investigated using immunohistochemical staining
      with reference to pathological features. The expression of Ki-67 antigen was also
      studied as a proliferation marker. RESULTS: Forty-seven cases were examined, and
      the overexpression of c-erbB-2 oncoprotein was revealed in 25 (53%) cases. It was
      not related both tumor grade (G) and tumor stage (pT). The overexpression of p53
      oncoprotein was revealed in 29 (62%) cases. There were 13 p53 positive cases in
      27 low grade (G1, G2) tumors, and 16 in 20 high grade (G3) tumors. There were
      also 8 p53 positive cases in 21 low stage (pTa, pT1) tumors, and 21 in 26 high
      stage (pT2-4) tumors. Thus, p53 oncoprotein was more frequently overexpressed in
      high grade tumors (p < 0.05) and in high stage tumors (p < 0.01). Ki-67 labelling
      index (LI, mean +/- SD) was 10.7 +/- 8.9 in low grade tumors and 26.3 +/- 12.5 in
      high grade tumors. It was also 9.0 +/- 8.1 in low stage tumors and 24.0 +/- 12.4
      in high stage tumors. Thus, Ki-67 LI was higher in high grade tumors (p < 0.01)
      and in high stage tumors (p < 0.01). The c-erbB-2 status and Ki-67 LI were not
      correlated, while the LI of p53 positive cases (21. 7 +/- 13.6) was significantly
      higher (p < 0.01) than it of p53 negative cases (10.3 +/- 8.5). The difference of
      LI between p53 positive cases and p53 negative cases was significant (p < 0.05)
      in low grade tumors, but in high grade tumors LI was higher than it of low grade
      tumors independently of p53 expression. CONCLUSION: p53 but not c-erbB-2 was
      considered to be associated with rapid tumor progression in renal pelvic and
      ureteral carcinoma and play an important role in its progression especially in
      low grade tumors.

PMID- 9234616
TI  - [A clinical study on combination therapy of antimicrobial agents for complicated
      urinary tract infection--with special reference to combination with
      clarithromycin].
AB  - PURPOSE: To confirm the clinical efficacy of the combined therapy to complicated
      urinary tract infection (UTI), we conducted a comparative clinical study of the
      combined therapy with ciprofloxacin (CPFX) and clarithromycin (CAM) acting an
      biofilm elimination or CPFX alone in patients with complicated UTI. PATIENTS AND
      METHODS: The study was carried out in patients with complicated UTI having WBCs
      with 5/hpf or more in urinary sediment and bacteriuria at least 10(4) CFU/ml. The
      combined therapy was CPFX and CAM, each 600 mg/day, for 14 days, and the single
      therapy group CPFX, 600 mg/day, for 14 days. On Day 7 and 14, the eradication
      rate and efficacy rate (according to the criteria of the Japanese UTI committee)
      were determined. In the patients with indwelling catheter, the surface of the
      catheter tip was observed under a scanning electron microscope (SEM) on Day 14.
      RESULTS: In both cases with and without catheters, clinical efficacy was higher
      in the combined therapy group than in the single therapy group. In particular,
      the efficacy rates at 14 Day were significantly higher in the former group.
      Furthermore, we investigated the therapeutic effect in the below MIC breakpoint
      of CPFX in complicated UTI. The combined therapy group showed a higher clinical
      efficacy in both cases with and without indwelling catheter than the single
      therapy group, although there was not statistically significant. Biofilm on the
      surface of the catheter tip was eliminated in 75% of the combined therapy group.
      However, none of the biofilm was eliminated in the single therapy group.
      CONCLUSION: From the above results, we surmise that the combined use of CPFX and
      CAM will show some degree of efficacy in eliminating both the causative organism
      and its biofilm in the complicated UTI.

PMID- 9234618
TI  - [Serum prostate-specific antigen in a urological outpatient clinic. Efficacy of
      age-specific and prostate volume-specific reference range in detection of
      prostate cancer].
AB  - BACKGROUND: Prostate specific antigen (PSA) is the most available marker for
      early detection of prostate cancer. Nevertheless, the standard upper range of PSA
      (4.0 ng/ml) does not demonstrate sufficient specificity. Thus, we evaluated the
      distribution of PSA by age and prostate volume in urological patients, and
      determined PSA reference ranges by the each parameter. Diagnostic efficacy was
      also evaluated. METHODS: Three-hundred-seventy-five patients who visited the
      urological outpatient clinic between January, 1994 and February, 1996, and were
      considered not to have prostate cancer, were analyzed PSA levels by age. Among
      them, two-hundred-seventy-six patients in whom prostate volumes were presumed by
      means of transabdominal ultrasonography, were evaluated a correlation of PSA
      values with prostate volumes. Using the age-specific and volume-specific
      reference ranges determined by this analysis, sensitivity, specificity, and
      positive predictive value were compared with those in case using the 0.0 to 4.0
      ng/ml reference range and the 0.0 to 11.7 ng/ml reference range, in 72 patients
      (cancer 24, noncancer 48) in whom histological examinations were performed in the
      same period. RESULTS: We found statistically significant slight correlations
      among age, prostate volume, and PSA. By using the age-specific reference range,
      volume-specific reference range, and 0.0 to 11.7 ng/ml reference range, we could
      elevate the specificity and positive predictive value approximately by 65% and
      35%, respectively, compared with those of the 0.0 to 4.0 ng/ml reference range.
      CONCLUSION: In order to decrease the number of rather invasive than necessary
      prostate biopsies, age-specific and volume-specific reference ranges are useful
      in urological outpatient clinic.

PMID- 9234619
TI  - [Proliferating character of inverted papilloma of the urinary bladder].
AB  - BACKGROUND: Inverted papilloma (IP) of the urinary bladder is generally
      considered to be a benign lesion by histological examination. In recent years,
      however, there have been several cases of IP simultaneously accompanied with
      transitional cell carcinoma (TCC), elsewhere in the bladder or combined as a
      single urothelial lesion. So we investigated proliferating character of IP by DNA
      ploidy analysis and immunohistostaining with proliferating cell nuclear antigen
      (PCNA). METHODS: Six cases of IP of the urinary bladder were analyzed and 12
      cases of TCC of G1 and G3 grade were included in this study as a control. As DNA
      ploidy analysis, all specimens were feulgen stained using CAS DNA staining kit
      and examined by image cytometry (CAS 200R system). For the PCNA
      immunohistochemistry, all specimens were stained with anti-PCNA monoclonal
      antibody (Novocastra Lab.: PC10) according to ABC (avidin-biotin-complex)
      standard method. We determined that the DNA Index of the case under 1.20 was
      diploid and the others was aneuploid. PCNA staining were determined by only one
      pathologist as follows: negative (-) and positive (+), (2+) and (3+). RESULTS: As
      DNA ploidy, 5 of 6 cases of TCC G3 group as a control were aneuploid. But in
      spite of all cases of TCC G1 group were diploid, among IP cases, only 1 out of 6
      was aneuploid. As PCNA staining, 2 of 6 in TCC G1 group and 5 of 6 in G3 group
      were positive. And it was noted examination was positive. CONCLUSION: There have
      been no recurrence since transurethral resection in all IP in the study including
      the case recognized as aneuploid and positive for PCNA staining. But the present
      results suggest that among IPs, considered generally as a benign tumor, the case
      which has high proliferating character exists.

PMID- 9234620
TI  - [Prognosis of renal cell carcinoma coexisting with renal cystic diseases--results
      of nation-wide survey in Japan].
AB  - OBJECTIVE: To study the outcome of the patients with renal cell carcinoma (RCC)
      coexisting with renal cystic disease. SUBJECTS AND METHODS: The nation-wide
      survey conducted in 1989 enrolled 223 patients with RCC coexisting with renal
      cystic disease. Of those 223, we could follow up 216 patients in the second
      survey in 1994. RESULTS: Renal cystic diseases coexisting with RCC included
      simple renal cysts in 69 cases, acquired cystic disease of the kidney (ACDK) in
      61, cystic RCC in 54, multilocular renal cysts in 19, polycystic kidney in 3,
      miscellaneous cysts in 9, and unspecified cyst in 1. The overall 5-year survival
      was 84%. The mean survival of the patients without any symptoms was significantly
      higher than that of those with symptoms. The survival of those with ACDK was
      lowest, and that will cystic RCC was highest. The survival was significantly
      different between the two groups, however the disease specific survival excluding
      the effect of dialysis was not significantly different between the two groups.
      Regarding TNM category, those with pT1 or pT2, comprising 87% of the subjects,
      carried a prognosis more favorable than those with pT3 or pT4. Among those
      undergoing cyst puncture (47 patients), positive cytology resulted in poorer
      prognosis. However, there was no such difference in the prognosis between
      punctured group and non-punctured group. CONCLUSION: Those with RCC coexisting
      with renal cystic disease carried a favorable prognosis. Cyst puncture were not
      concluded to exert an unfavorable effect on the prognosis at least in this study.

PMID- 9234621
TI  - [Pregnancy after augmentation cystoplasty. A case report].
AB  - A 31-year-old woman with a history of spina bifida occulta became pregnant after
      ileocystoplasty for her neurogenic bladder. During the pregnancy she had frequent
      episodes of febrile urinary tract infections, and progressive hydronephrosis
      appeared in the second trimester. At 25 weeks gestation she was complicated by
      severe pyelonephritis requiring the intervention with the placement of double
      pigtail ureteral stent. However, long term efficacy of ureteral stent was
      questionable and this indwelling catheter caused bacteriuria which was not
      eradicated by intravenous antibiotics. Classical cesarean section was performed
      at 32 weeks of gestation due to the fear of fetal distress. Neobladder and
      mesenteric blood supply were adherent to the anterior surface of the uterus.
      Urinary tract infection is extremely common during pregnancy after
      enterocystoplasty. The most important point is prophylactic antibiotics
      throughout the pregnancy. At the time of cesarean section, a reconstructive
      urological surgeon should be part of the operative team and take great care to
      avoid injury to the blood supply of cystoplasty.

PMID- 9234622
TI  - [A case of hormone-refractory prostate cancer responsive to low-dose prednisolone
      therapy].
AB  - A 67-year-old man with hormone-refractory (stage D2) prostate cancer was admitted
      to the hospital because of general malaise and bone pain. The patient had been
      receiving hormonal therapy, which was discontinued after admission. Instead, 10
      mg per day of prednisolone was administered orally. His symptoms improved, and
      the serum prostate specific antigen (PSA) level decreased markedly. After 18
      weeks of treatment with prednisolone, the serum PSA level rose again, and bone
      pain worsened. The patient died of cancer one month later.

PMID- 9234623
TI  - [Role of endothelin-B receptors in the pulmonary circulation].
AB  - Endothelin-1 (ET-1) is a potent vasoactive peptide and is thought to play an
      important role in the regulation of vascular tone. ET-1 can both constrict blood
      vessels, via endothelin-A (ET-A) receptors in vascular smooth muscle cells, and
      dilate then via endothelin-B (ET-B) receptors in endothelial cells in the
      systemic circulation. To determine the role of ET-B receptors in the pulmonary
      circulation, we examined the hemodynamic effects of a selective ET-B receptor
      agonist (IRL 1620) in rats. In rat lungs perfused with a salt solution, IRL 1620
      caused pulmonary vasoconstriction in a dose-dependent manner. In lungs perfused
      with a hypoxic half-blood solution (10% O2), doses of IRL 1620 less than 10 nM
      caused pulmonary vasodilation, but higher doses caused pulmonary
      vasoconstriction. IRL 1620 caused transient vasodilation of the systemic
      circulation at every dose used (0.1, 1, and 5 nmol/kg) in anesthetized rats. In
      contrast, the effects of IRL 1620 on the pulmonary circulation varied with the
      dose. Small doses (0.1 or 1 nmol/kg) caused pulmonary vasodilation, but a higher
      dose (5 nmol/kg) caused pulmonary vasoconstriction. These results show
      tachyphylaxis in the pulmonary vasodilator response to IRL 1620, but not in the
      systemic vasodilator response. The present data show the dual action
      (vasoconstriction and vasodilation) of ET-B receptors.

PMID- 9234624
TI  - [A new handpiece attachment for Nd:YAG laser ablation of emphysematous bullae].
AB  - Recently, attention has been drawn to lung volume reduction for bullous emphysema
      by wedge excision or laser ablation. We used a neodymium: yttrium-aluminum garnet
      (Nd:YAG) laser with a free-beam mode to ablate peripheral emphysematous areas of
      lung tissue. To aid us in this procedure, we developed an attachment consisting
      of a stainless steel rod 3 cm in effective length, with a 1.8-cm diameter ring
      attached to its tip, and installed it on the tip of the laser handpiece used for
      free-beam laser ablation. This device has the following distinct advantages: 1)
      the distance between the tip of the laser and the pleura can easily be held
      constant, 2) the angle of irradiation can easily be maintained at 90 degrees.
      These result in 3) a constant area of irradiation (one square centimeter), and 4)
      an irradiated area that is clearly distinguished by the ring. In addition, the
      attachment is 5) simple and easy to construct. Three patients with bullous
      emphysema underwent unilateral laser ablation of the visceral pleura with the new
      device. All patients recovered completely. We found this rod-and-ring attachment
      to be useful for free-beam laser ablation.

PMID- 9234625
TI  - [Lung lobar volume in patients with chronic interstitial pneumonia].
AB  - We measured lung lobar volume by using helical computed tomography (HCT) in 23
      patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic
      interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5
      healthy volunteers. HCT scanning was done at the maximal inspiratory level and
      the resting end-expiratory level. To measure lung lobar volume, we traced the
      lobar margin on HCT images with a digitizer and calculated the lobar volume with
      a personal computer. The lower lobar volume and several factors influencing it in
      chronic interstitial pneumonia were studied. At the maximal inspiratory level,
      the lower lobar volume as a percent of the whole lung volume was 46.8 +/- 4.13%
      (mean +/- SD) in the volunteers, 39.5 +/- 6.19% in the patients with IIP, and
      27.7 +/- 7.86% in the patients with CVD-IP. The lower lobar volumes in the
      patients were significantly lower than in the volunteers. Patients with IIP in
      whom autoantibody tests were positive had lower lobar volumes that were very low
      and were similar to those of patients with CVD-IP. These data suggest that
      collagen vascular disease may develop in patients with interstitial pneumonia.
      The patients with IIP who had emphysematous changes on the CT scans had smaller
      decreases in total lung capacity and lower ratios of forced expiratory volume in
      one second to forced vital capacity than did those who had no emphysematous
      changes, those two groups did not differ in the ratio of lower lobar volume to
      whole lung volume. This suggests that emphysematous change is not factor
      influencing lower lobar volume in patients with chronic interstitial pneumonia.
      We conclude that chronic interstitial pneumonia together with very low values for
      lower lobar volume may be a pulmonary manifestation of collagen vascular disease.

PMID- 9234626
TI  - [Five cases of pneumonitis induced by sho-saiko-to].
AB  - We report five cases of pneumonitis induced by sho-saiko-to. The patients
      complained of coughing (4/5), dyspnea (4/5), and pyrexia (3/5). The duration of
      sho-saiko-to treatment ranged from 4 to 1155 days. Abnormal laboratory findings
      included high levels of C-reactive protein (4/5), leucocytosis (4/5), severe
      hypoxemia (4/5), low vital capacity (3/5), and low diffusing capacity (5/5).
      Chest X-ray and CT films revealed diffuse reticulonodular or ground-glass shadows
      in both lung fields (4/5). Bronchoalveolar lavage was done in three cases, and
      revealed lymphocytosis in two cases and abnormally low CD4/8 ratios in three
      cases. The results of lymphocyte stimulation tests against sho-saiko-to and its
      component were positive in 3 of 5 cases. After discontinuation of sho-saiko-to,
      corticosteroids were given in all cases. Symptoms were relieved, and laboratory
      data and chest X-ray findings returned forward normal. Sho-saiko-to toxicity
      should be included in the differential diagnosis of pneumonitis. If drug-induced
      pneumonitis is suspected, administration of sho-saiko-to should be stopped and
      corticosteroid therapy should be given immediately.

PMID- 9234627
TI  - [Survival and pulmonary hemodynamics in patients with sequelae of pulmonary
      tuberculosis who received home oxygen therapy].
AB  - We studied the relationship between survival and pulmonary hemodynamics in
      patients with sequelae of pulmonary tuberculosis. We also studied the effect of
      home oxygen therapy (HOT) on pulmonary hemodynamics in those patients. The
      subjects were 59 patients who were treated with HOT after right-heart
      catheterization. Blood gases and pulmonary hemodynamics were measured twice:
      while the patients breathed air and after they had inhaled pure oxygen. In 11
      patients, right-heart catheterization done before and after HOT was begun. Before
      HOT was begun, 49 patients were given the diagnosis of pulmonary hypertension,
      but the difference in survival between those who had and those who did not have
      pulmonary hypertension was not statistically significant. Mean pulmonary artery
      pressure fell by more than 5 mmHg after inhalation of pure oxygen in 5 patients
      (responders), but survival did not differ between responders and non-responders.
      Blood-gas volumes and pulmonary hemodynamics did not differ between those who
      died within 2 years after right-heart catheterization and those who lived for
      more than 5 years. Pulmonary arterial resistance and mean pulmonary artery
      pressure decreased significantly after HOT was begun. HOT can reduce mean
      pulmonary artery pressure in patients with sequelae of pulmonary tuberculosis,
      but survival on HOT is not related to the presence of pulmonary hypertension or
      to the effect of pure oxygen on mean pulmonary artery pressure.

PMID- 9234628
TI  - [Exercise performance and body composition in patients with chronic obstructive
      pulmonary disease].
AB  - Malnutritions is one cause of exercise intolerance in patients with chronic
      obstructive pulmonary disease. We studied the relation between exercise
      limitation and body composition in 20 clinically stable patients with chronic
      obstructive pulmonary disease. Maximal work capacity was measured during
      incremental exercise on a cycle ergometer, along with maximal oxygen uptake.
      Anaerobic threshold was determined by the V-slope method. Bone mineral content,
      lean mass, and fat mass were assessed by dual-energy X-ray absorptiometry. Bone
      mineral content and lean mass were significantly lower in moderately malnourished
      patients (%IBW < 80) than in well-nourished patients (%IBW > or = 90). Fat mass
      was significantly lower in mildly malnourished patients than in well-nourished
      patients. Maximal work capacity, maximal oxygen uptake, and anaerobic threshold
      correlated significantly with lean mass, but not with fat mass. These data
      suggest that lean mass is one determinant of exercise capacity in patients with
      chronic obstructive pulmonary disease.

PMID- 9234629
TI  - [Bronchiolitis obliterans and no radiographic abnormalities in a patient with
      rheumatoid arthritis].
AB  - A 53-year-old woman was given a diagnosis of rheumatoid arthritis in 1988, and
      begun treatment with D-penicillamine in September 1992. She noticed dry coughing
      and exertional dyspnea that began in April 1993. Chest X-ray and CT films
      revealed no abnormal opacities. However, bronchiolitis obliterans was suspected
      because of a low FEV1% (23%). Examination of specimens obtained by thoracoscopic
      lung biopsy revealed constrictive obliteration by granulation tissue in proximal
      bronchioles and follicular bronchiolitis. Alveoli and respiratory bronchioles
      were intact. After corticosteroid and cyclophosphamide pulse therapy, FEV1%
      increased to 35%. At the time of this writing she was alive 2.5 years after
      hospitalization.

PMID- 9234630
TI  - [Chronic eosinophilic pneumonia associated with allergy to candida and with
      changes in bronchoalveolar lavage fluid].
AB  - A 61-year-old woman was admitted to the hospital with the chief complaints of
      fever, coughing, and shortness of breath. A chest X-ray film revealed infiltrates
      in both upper lung fields. A specimen was obtained by transbronchial lung biopsy
      and chronic eosinophilic pneumonia was diagnosed. The patient' s condition
      improved after the start of corticosteroid therapy. A relapse occurred, and
      corticosteroid therapy was again successful. Because an environmental provocation
      test was positive, allergological examinations were done. An intradermal test for
      sensitivity to candida was positive, as was a test for precipitation of
      antibodies to candida. In addition, an inhalation provocation test with candida
      antigen was positive. Therefore, allergy to candida was believed to have caused
      this patient's symptoms. Bronchoalveolar lavage was done three times. Eosinophils
      predominated in the first sample, but lymphocytes predominated in the last two.
      This raises the possibility that chronic eosinophilic pneumonia and bronchiolitis
      obliterans organizing pneumonia might change into each other.

PMID- 9234631
TI  - [Status asthmaticus treated with inhaled isoflurane and intravenous
      isoproterenol].
AB  - We report the case of an 18-year-old man with status asthmaticus who was treated
      with inhaled isoflurane and intravenous isoproterenol. The patient was intubated
      and mechanical ventilation was began immediately after admission to the hospital.
      He received intravenous methylprednisolone and aminophyline, and frequent
      inhalation of isoproterenol aerosol. However, his respiratory status
      deteriorated: peak inspiratory pressure increased markedly, and right
      pneumothorax, right lower lobe atelectasis, and hypotension developed. He was
      then given isoflurane by inhalation and a continuous intravenous infusion of
      isoproterenol, which was followed by marked improvement in his respiratory and
      hemodynamic status. Isoflurane can be effective in patients with status
      asthmaticus, and it does not increase the arrhythmogenicity of catecholamines.
      Intravenous administration of isoproterenol can also be useful in the treatment
      of patients with status asthamticus. The combination of isoflurane with
      intravenous isoproterenol may be useful when status asthmaticus is hard to
      control with conventional therapy.

PMID- 9234632
TI  - [Successful treatment of hypereosinophilic syndrome with cyclosporin and
      steroids].
AB  - A 41-year-old man with severe hypereosinophilic syndrome was first given a high
      dose of steroids. His condition improved, and the dose of steroids was tapered.
      His condition then worsened, and administration of cyclosporin was begun. Disease
      activity decreased and eosinophil counts decreased to the normal range.
      Cyclosporin and steroids inhibit the interleukin-2 gene transcription factors NF
      AT and AP-1. They also inhibit the interleukin-5 production by peripheral
      lymphocytes stimulated by interleukin-2. AP-1 is the primary target for steroid
      mediated repression of IL-2 gene transcription, but NF-AT appears to be the main
      target of cyclosporin. In patients with the hypereosinophilic syndrome,
      cyclosporin can be effective and can minimize the adverse effects of long-lasting
      therapy with high doses of steroids.

PMID- 9234633
TI  - [Spontaneous resolution of primary pulmonary cryptococcosis].
AB  - A 22-year-old man underwent chest roentgenography to obtain a health certificate,
      and the film showed a nodular lesion in the left lung. Computed tomography of the
      chest revealed a 25 x 20 mm nodular lesion in the S4 segment of the left lung.
      Fiberoptic bronchoscopy was done and transbronchial biopsy specimens showed
      fungal elements consistent with Cryptococcus. Further examinations, including
      cereberospinal fluid examination, were negative. This patient's pulmonary
      cryptococcal lesion resolved without treatment and without complications.

PMID- 9234634
TI  - [Successful treatment of chronic eosinophilic pneumonia with suplatast tosilate].
AB  - The patient was a 59-year-old woman who complained of coughing, sputum
      production, and dyspnea. Abnormal moving shadows were found by chest radiography.
      There was prolonged eosinophilia in blood. Eosinophilia was also found in
      bronchoalveolar lavage fluid, and examination of a specimen obtained by
      transbronchial lung biopsy revealed eosinophil infiltration in alveolar septal
      walls, which led to a diagnosis of chronic eosinophilic pneumonia. Because of an
      attack of bronchial asthma and a high level of IL-5 in serum on admission, the
      patient was given suplatast tosilate. Symptoms were relieved, eosinophil counts
      in blood and in bronchoalveolar lavage fluid decreased, and the radiographic
      abnormality disappeared. The patient was not treated with steroids, and there has
      been no reccurrence to date, one year after discharge.

PMID- 9234635
TI  - [Chronic interstitial pneumonia and crescentic glomerulonephritis associated with
      perinuclear antineutrophil cytoplasmic antibodies].
AB  - We examined a 72-year-old man suffering from chronic interstitial pneumonia with
      crescentic glomerulonephritis associated with perinuclear antineutrophil
      cytoplasmic antibodies (P-ANCA). Ten years before admission, he was given a
      diagnosis of interstitial pneumonia, but received no medication. He was admitted
      to our hospital because of a high fever and back pain. Antibiotics were used, but
      without success. The serum P-ANCA titer was high, and examination of a kidney
      biopsy specimen showed crescentic glomerulonephritis. Computed tomography of the
      chest showed that the lungs had a honecomblike appearance, and examination of a
      specimen obtained by transbronchial lung biopsy showed interstitial fibrosis.
      This case shows that interstitial pneumonia can be associated with P-ANCA. It is
      important to be a wore that crescentic glomerulonephritis associated with P-ANCA
      can develop in patients with interstitial pneumonia.

PMID- 9234636
TI  - [Idiopathic interstitial pneumonia associated with a high level of CA19-9 in
      serum and with CA19-9 in lung tissue].
AB  - A 65-year-old man was admitted to our hospital because of mild dyspnea. A chest
      roentgenogram showed diffuse reticulonodular shadows in both lung fields. The
      concentration of CA19-9 in serum was high. Pancreatic cancer and other diseases
      were considered as causes, but no definitive diagnosis could be made. An open
      lung biopsy was done, and examination of a specimen resulted in the diagnosis of
      idiopathic interstitial pneumonia (chronic type). Immunohistochemical staining
      with anti-CA19-9 antibody was positive. The lumens of microscopic honeycomb
      structures and fibrotic areas were covered with flattened and cuboidal
      metaplastic epithelial cells, which stained positively for anti-CA19-9 antibody.

PMID- 9234637
TI  - [Legionella pneumonia successfully treated despite late diagnosis].
AB  - Status asthmaticus developed in a 72-year-old man who was being treated with oral
      prednisolone for severe persistent asthma. The dosage of prednisolone was
      increased, and amikacin was injected to treat pneumonia that had developed in the
      right lung. Progressive pulmonary infiltrates, respiratory compromise, and
      hypoxemia developed, and the patient eventually required mechanical ventilation.
      Antibiotic treatment was changed to imipenem/cilastatin, piperacillin,
      gentamicin, clarithromycin, erythromycin, and minocycline. Liver injury
      developed. More than one month after the patient was admitted, Legionella
      pneumonia was diagnosed. Levofloxacin (400 mg/day) was then given orally, in
      combination with injected imipenem/cilastatin. Liver function did not
      deteriorate, and the pneumonia resolved. Most diagnoses of Legionnaires' disease
      are made retrospectively by examination of serum. In this case, antibiotics
      active against Legionella pneumophila had been used before the diagnosis was
      established, which probably contributed to the patient's recovery. When
      aminoglycosides or beta-lactam antibiotics are ineffective, administration of
      agents effective against Legionnaires' disease should be considered.

PMID- 9234638
TI  - [Thymic carcinoma associated with pulmonary sarcoidosis].
AB  - A 54-year-old man who worked as a farmer was admitted to the hospital in August
      1989 because of bilateral hilar adenopathy that was detected during a mass
      screening. Laboratory examination showed a high serum lysozyme level and the PPD
      skin test was negative. Examination of a specimen obtained by transbronchial lung
      biopsy revealed non-caseous epithelioid cell granuloma. Sarcoidosis was
      diagnosed. The patient was not treated, and the bilateral hilar adenopathy had
      lessened by 1992. The patient was readmitted to our hospital because of right
      hilar and upper mediastinal enlargement seen on a chest radiograph in April 1994.
      Computed tomography and magnet resonance imaging disclosed an anterior
      mediastinal tumor in contact with the right upper lobe, the left inominate vein,
      and the pericardium. Bronchoscopy showed no abnormality in the right upper-lobe
      bronchus. Examination of a specimen obtained from the B3b bronchus showed no
      evidence of malignant cells. Examination of a tumor specimen obtained by
      transdermal biopsy showed squamous cell carcinoma. After the patient underwent
      combination chemotherapy, the tumor ws resected, along with the right upper lobe,
      the left inominate vein, and the pericardium, which were difficult to separate
      from the tumor. Postoperative pathological examination showed that squamous cell
      carcinoma was intermingled with normal thymus tissue. We believe that squamous
      cell carcinoma originated in the thymus. Non-caseous epithelioid cell granulomas
      were also found in the resected right upper lobe and in a mediastinal lymph node.
      The patient was discharged after post-operative irradiation of the mediastinum.
      Thymic carcinoma is rare, and sarcoidosis in a patient with thymic carcinoma is
      very rare. T lymphocytes are very important in the pathogenesis of sarcoidosis,
      and the thymus is involved in the growth and differentiation of T lymphocytes.
      The occurrence of these two diseases in one patient is interesting, but the
      relationship is not clear.

PMID- 9234639
TI  - [Small cell lung cancer with acute monocytic leukemia after combined chemotherapy
      including etoposide].
AB  - Small cell lung cancer (stage IIIB) developed in a 61-year-old woman. She was
      treated with chemotherapy in which the cumulative dose of carboplatin was 662
      mg/m2 and that of etoposide was 2,000 mg/ m2, and with concurrent irradiation in
      which the total dose of X-rays was 44.8 Gy. The response to chemotherapy and
      irradiation was very good. Radiation pneumonitis developed after discharge, but
      it resolved after steroid therapy. Nine months after the diagnosis of lung cancer
      the patient was readmitted because of bleeding and leukocytosis. Acute monocytic
      leukemia (M5a) was diagnosed after examination of a bone-marrow aspirate. The
      patient was treated with chemotherapy, but she died of severe bone-marrow
      suppression and multiple organ failure 3 months after the diagnosis of acute
      monocytic leukemia. Although chromosome analysis could not be done, we strongly
      suspect that this leukemia was induced by etoposide, because of the clinical
      course.

PMID- 9234640
TI  - [Esophagobronchial fistula and empyema resulting from esophageal carcinoma].
AB  - A 59-year-old woman was admitted to the hospital with a one-month history of
      hemoptysis, generalized fatigue, and a high fever. A chest X-ray film obtained on
      admission showed a massive right-sided pleural effusion. Examination of an
      aspirate showed a high level of amylase, and bacteria that were the same as oral
      bacteria. Closed drainage yielded ichorous pus and food residues, which led us to
      the diagnosis of empyema caused by esophageal perforation. Esophagography and
      fiberoptic esophagoscopy revealed that an esophagobronchial fistula related to an
      advanced esophageal carcinoma had caused the empyema. Surgical resection was
      done, and the patient was alive at the time of this writing, 7 months after she
      was first treated. Esophageal carcinoma is sometimes accompanied by
      esophagobronchial fistula. Patients with this condition usually have severe
      respiratory symptoms; those presenting with empyema are rare. Esophageal
      carcinoma must be carefully ruled out as the cause of empyema.

PMID- 9234641
TI  - [Molecular mechanism of nuclear protein import].

PMID- 9234642
TI  - [Immunoregulatory functions of Fc receptors].

PMID- 9234643
TI  - [Sorting in the TGN into different transport routes to the plasma membrane in
      fibroblasts].

PMID- 9234644
TI  - [Various physiological functions suggested for protein cross-linking enzyme,
      transglutaminase].

PMID- 9234645
TI  - [Mechanism of catecholamine-induced lipolysis in adipocytes].

PMID- 9234646
TI  - [TGF-beta signal transduction and Smad].

PMID- 9234647
TI  - [Atomic force microscopy for biochemist].

PMID- 9234648
TI  - [Purification and biochemical properties of thrombopoietin].

PMID- 9234649
TI  - Yohimbine elimination in normal volunteers is characterized by both one- and two
      compartment behavior.
AB  - We sought to determine the safety, pharmacodynamic response, and single- and
      multiple-dose pharmacokinetic profile of yohimbine hydrochloride. Thirty-two
      healthy volunteers received 6 days of yohimbine, 5.4 mg 3 times daily (t.i.d.),
      10.8 mg t.i.d., 16.2 mg t.i.d., or 21.6 mg twice daily (b.i.d.), with
      determination of plasma catecholamine levels and mood/anxiety-inventory scores.
      The pharmacokinetic profile of yohimbine was determined after the first and last
      dose. Yohimbine exhibited one-compartment elimination in most subjects, with dose
      dependent increases in maximal concentration (Cmax) and area under the curve
      (AUC) but no evidence of drug accumulation. At least two subjects in each cohort
      exhibited two-compartment elimination of yohimbine, with nonsignificant increases
      in day 7 AUC, Cmax, and terminal elimination half-life (t1/2beta). Plasma
      catecholamine levels increased significantly in relation to both average
      yohimbine AUC and Cmax, but there were no significant effects on heart rate,
      blood pressure, or anxiety/mood-inventory scores. The single- and multiple-dose
      pharmacokinetic profile of yohimbine exhibits a substantial degree of
      interpatient and intrapatient variability, possibly resulting from variability in
      first-pass and hepatic metabolism. There is a significant correlation between
      plasma norepinephrine levels and yohimbine AUC or Cmax. Further multiple-dose
      studies are warranted definitively to address the relation between yohimbine AUC
      or Cmax and pharmacologic effect.

PMID- 9234650
TI  - Cardiovascular and renal actions of the endothelin(B) receptor in pigs.
AB  - Previously we showed that blocking the endothelin (ET)A receptor subtype with BQ
      153 inhibited the vasoconstrictor effects of intravenously administered ET-1. In
      the presence of the ET(A) antagonist, ET-1 produced marked reductions in
      myocardial contractility and renal blood flow. We postulated that either the
      ET(B) receptor, or some other, as yet unidentified, ET-receptor subtype mediated
      the observed hemodynamic changes. In anesthetized pigs, this hypothesis was
      tested by using a recently developed selective, high-affinity antagonist to the
      ET(B) receptor, BQ-788, and sarafotoxin S6c, a selective ET(B) agonist, to
      determine the contribution of this receptor subtype to cardiovascular function.
      Endothelin-1 (0.4 nmol/kg, i.v.) produced the characteristic biphasic hemodynamic
      responses, consisting of an initial transient reduction in mean arterial pressure
      (MAP; 83 +/- 3 to 72 +/- 4 mm Hg; n = 9) followed by a prolonged increase (112 +/
      4 mm Hg; p < 0.01). As well, cardiac output (-58%; p < 0.05), myocardial
      contractility (-19%; p < 0.01), and renal blood flow (63%; p < 0.05) decreased.
      Sarafotoxin S6c produced marked but transient reductions in MAP (p < 0.001),
      cardiac output (p < 0.01), myocardial contractility (p < 0.001), and renal blood
      flow (p < 0.05). BQ-788 (1.0 mg/kg, i.v.), administered 3 min before sarafotoxin
      S6c, inhibited its effects. BQ-788 also inhibited the initial transient reduction
      in MAP seen after the injection of ET-1, but the subsequent sustained pressor
      responses were enhanced as reflected in the greater increases in left ventricular
      pressure (p < 0.02), myocardial contractility (p < 0.05), MAP (p < 0.01), and a
      larger reduction in cardiac output (p < 0.05). The heart rate was not changed
      after the initial ET injection, but it increased 54% when the peptide was
      administered in the presence of BQ-788. The reduction in renal blood flow was
      still evident, and its magnitude (64%) remained the same (p < 0.01) after
      treatment with BQ-788. Only the combined administration of both the ET(A) (BQ
      123) and ET(B) (BQ-788) receptor antagonists blocked the effects of ET-1 on renal
      blood flow (p < 0.05). These data confirm that BQ-788 is a selective and
      effective antagonist of the ET(B) receptor and show that activation of this
      receptor subtype is involved in the transient vasodilation provoked by ET-1.
      Additionally, the ET(B) receptor appears to oppose the vasoconstrictor effects of
      the ET(A) receptor, which clearly mediates vasoconstriction. Combined treatment
      with BQ-123 and BQ-788 attenuated the reductions in renal blood flow produced by
      ET-1. Furthermore, some actions of ET-1 were not blocked by these antagonists and
      cannot be attributed to either the ET(A) or ET(B) receptors. We hypothesize the
      existence of an additional ET receptor or a subtype of the ET(B) receptor that is
      insensitive to BQ-788.

PMID- 9234651
TI  - The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents
      and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular
      remodeling in Sprague-Dawley rats.
AB  - Exposure to hypoxia is associated with increased pulmonary artery pressure and
      plasma endothelin (ET-1) levels and with selective enhancement of ET-1 peptide
      and messenger RNA (mRNA) and endothelin-A (ET-A) receptor mRNA in rat lung. Our
      study tested the hypothesis that A-127722, an orally active antagonist of the ET
      A receptor, can prevent hypoxia-induced pulmonary hypertension and vascular
      remodeling in the rat. Pretreatment with A-127722 (3, 10, and 30 mg/kg/day in
      drinking water for 2 days) caused dose-dependent inhibition of the pulmonary
      vasoconstrictor response to short-term hypoxia (10% O2, 90 min). Long-term A
      127722 treatment (10 mg/kg/day in drinking water for 2 weeks) instituted 48 h
      before hypoxic exposure attenuated the subsequent development of pulmonary
      hypertension, the associated right atrial hypertrophy, and pulmonary vascular
      remodeling. Institution of A-127722 treatment (10 mg/kg/day in drinking water for
      4 weeks) after 2 weeks of hypoxia retarded the progression of established hypoxia
      induced pulmonary hypertension and right atrial hypertrophy and reversed the
      pulmonary vascular remodeling despite continuing hypoxic exposure. These findings
      support the hypothesis that endogenous ET-1 plays a major role in hypoxic
      pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary
      vascular remodeling and suggest that ET-A receptor blockers may be useful in the
      treatment and prevention of hypoxic pulmonary hypertension in humans.

PMID- 9234652
TI  - Verapamil accelerates the transition to heart failure in obese, hypertensive,
      female SHHF/Mcc-fa(cp) rats.
AB  - We sought to characterize the effects of the nonselective Ca2+ channel
      antagonist, verapamil, and the vascular-selective Ca2+ channel antagonist,
      felodipine, on obese, hypertensive, heart failure-prone, female SHHF/Mcc-fa(cp)
      rats. Rats were treated for < or = 2 months with verapamil (57 mg/kg/day) or
      felodipine (24 mg/kg/day). Blood pressures were determined at monthly intervals
      by the tail-cuff method. Heart weights and myosin isoforms were measured at the
      end of treatment. Direct cardiac effects of verapamil and felodipine were
      examined in electrically field stimulated, fura-2/AM-loaded cardiomyocytes. Both
      Ca2+ channel antagonists reduced systolic blood pressures. Verapamil, but not
      felodipine, increased heart weights and decreased expression of the myosin V1
      isoform. In older animals, 75% of those treated with verapamil developed end
      stage congestive heart failure. Age-matched control and felodipine-treated rats
      remained healthy. In isolated cardiomyocytes, 10(-9) M verapamil significantly
      reduced Ca2+ transient amplitudes but 10(-9) M felodipine did not. Both Ca2+
      channel antagonists reduced blood pressures in obese, hypertensive, female SHHF
      rats. Verapamil, but not felodipine, produced heart failure in a large number of
      these animals. Differences between the in vivo effects of the two Ca2+ channel
      antagonists may be related to the differing effects on sarcolemmal Ca2+ influx.

PMID- 9234653
TI  - Measurement of adenylylcyclase activity in the AV nodal region of the canine
      heart: evidence for inhibition by adenosine and acetylcholine.
AB  - Although it is essential to cardiac conduction, little is known about the
      biochemistry underlying postreceptor adrenergic, cholinergic and purinergic
      processes in the AV node. To study these mechanisms, we adapted a new and highly
      sensitive fluorometric assay for cyclic adenosine monophosphate (AMP) to
      characterize regional adenylylcyclase activity (cyclic AMP production in
      pmol/min/mg of protein) in membrane preparations made from 20-50 pieces of freeze
      dried, 20-microm thick, microdissected samples of tissue from canine right
      atrium, the AV nodal region, and left ventricle. Basal and NaF-stimulated
      adenylylcyclase activity (mean +/- SEM, n = 6) were 7.2 +/- 0.4 and 72.4 +/- 7.5
      in atrial, 15.6 +/- 1.3 and 58.8 +/- 4.7 in AV nodal, and 6.4 +/- 0.9 and 66.7 +/
      5.0 in ventricular tissues, respectively. Isoproterenol (10(-7)-10(-4) M)
      increased adenylylcyclase activity in a dose-dependent fashion in three different
      regions. The isoproterenol (10(-6) M)-stimulated adenylylcyclase activity (n = 6)
      was 14.4 +/- 1.3 in atrial, 21.9 +/- 1.6 in AV nodal and 13.4 +/- 1.4 in
      ventricular tissues. Adenosine (10(-3) M) and carbachol (10(-5) M) inhibited
      isoproterenol (10(-6) M)-stimulated adenylylcyclase activity to 10.1 +/- 1.1,
      12.9 +/- 1.3 in atrial, 15.1 +/- 1.6, 15.5 +/- 1.2 in AV nodal, and 7.5 +/- 0.7,
      11.9 +/- 1.2 in ventricular tissues, respectively. The results demonstrate that
      there are regional differences in adenylylcyclase activity under basal conditions
      and after adrenergic, purinergic, and cholinergic stimulation in the heart.
      Unlike adenosine, the inhibitory effects of cholinergic stimulation appear to be
      more specific for the AV node.

PMID- 9234654
TI  - ANF system in the newborn piglet pulmonary vessels.
AB  - The atrial natriuretic factor (ANF) induces diuresis, natriuresis, and
      vasodilation. Although it was originally found to be secreted from the atria, ANF
      synthesis has been demonstrated in other organs. The adult lung is not only the
      first target organ for ANF, but it also expresses the ANF gene and synthesizes,
      releases, and clears ANF from the circulation. We have shown the presence of ANF
      in human fetal lungs and also demonstrated that these lungs can release bioactive
      ANF. However, the role of the ANF system in the newborn lung is unknown.
      Therefore we studied the ANF system in pulmonary vessels (arteries and veins
      dissected from the hilum down to a 100-microm diameter), in isolated perfused
      lungs, and in the plasma from pulmonary artery and vein of 1- and 7-day-old
      piglets. High-performance liquid chromatography (HPLC) revealed the presence of
      both the mature peptide and the ANF prohormone in pulmonary vein microsomes, but
      in pulmonary arteries, only the mature form was identified. Furthermore, in the
      veins, the ANF content tended to be higher in 7- than in 1-day-olds. ANF caused a
      dose-dependent decrease in perfusion pressure (p < 0.05). In veins and arteries,
      most of the ANF receptors were of the type A guanylate cyclase as opposed to
      clearance receptors. Interestingly, the ANF receptors were fewer in veins, where
      synthesis takes place, than in arteries (p < 0.05). Significant circulating ANF
      plasma levels were measured by radioimmunoassay in both pulmonary artery and
      vein. However, there was no site difference in ANF plasma levels, suggesting that
      ANF is cleared and synthesized in the pulmonary vessels. In conclusion, the
      entire ANF system is present in the newborn piglet pulmonary vessels. The paucity
      of clearance receptors compared with functional receptors potentiates the role of
      ANF in the regulation of postnatal pulmonary vascular resistance.

PMID- 9234655
TI  - Reversal of endothelin-induced vasoconstriction by endothelium-dependent and 
      independent vasodilators in isolated hearts and vascular rings.
AB  - Endothelin (ET-1) is a potent endogenous vasoconstrictor. Several factors
      increase ET-1 release in vitro and ET-1 levels increase in vivo in situations
      that damage blood vessels. The aim of this study was to test the activity of
      several differently acting vasodilator drugs on reversing or attenuating the
      vasoconstrictor effects of exogenously administered ET-1 in isolated guinea-pig
      hearts, in isolated rings with intact endothelium from canine middle cerebral and
      basilar arteries, and from guinea-pig aortas. Vasodilator drugs tested up to
      maximal concentrations were adenosine (ADE), nitroprusside (NP), acetylcholine
      (ACH), nifedipine (NIF), and butanedione monoxime (BDM), an excitation-uncoupling
      agent. Variables measured in isolated hearts included coronary flow, percentage
      oxygen extraction (% O2E), left ventricular pressure (LVP), and myocardial oxygen
      consumption. It was found that ADE, NP, ACH, and BDM each attenuated the 60%
      decrease in coronary flow and 20% increase in % O2E elicited by 0.5 nM ET-1 in
      isolated hearts, but only BDM restored coronary flow, whereas BDM and ADE both
      restored % O2E. In isolated rings constricted with 20 nM ET-1, BDM restored tone
      equivalent to that by papaverine, whereas NP and NIF only attenuated the
      vasoconstriction elicited by ET-1. Ring experiments also demonstrated that the
      vasodilatory effect of BDM was independent of nitric oxide-dependent pathways and
      that BDM attenuated vasoconstriction resulting from increased bath KCl. The study
      suggests that drugs affecting intracellular Ca2+ with a mechanism of action
      downstream from cell-membrane receptors or intracellular messengers may be more
      effective for reversing the constrictor effect of ET-1. NP, however, would be a
      better clinical choice for reversing ET-1-induced vasoconstriction.

PMID- 9234656
TI  - Enhanced depressor effect of centrally administered high-calcium solution in salt
      loaded experimental hypertension.
AB  - The depressor effect by oral calcium supplementation is known to be more
      pronounced in salt-dependent than in renin-dependent hypertension. This study was
      conducted to investigate the role of central calcium on two different
      pathophysiologic subtypes of experimental hypertension; (a) salt-dependent,
      deoxycorticosterone acetate-salt hypertensive rats (DOCA), and (b) renin
      dependent, 2-kidney, 1 clip (2-K, 1C) hypertensive rats. In DOCA (n = 10), high
      calcium solution (Ca+2, 65.2 mM, 10 microl) given centrally (i.c.v.) elicited a
      marked decrease in mean blood pressure (MBP; 170 +/- 4 to 138 +/- 5 mm Hg, p <
      0.01) with a decrease in heart rate (HR; 390 +/- 18 to 344 +/- 17 beats/min, p <
      0.05) lasting for 40 min. In 2-K, 1C (n = 10), high-Ca2+ i.c.v. showed a lesser
      decrease in MBP (178 +/- 4 to 171 +/- 5 mm Hg) and HR (419 +/- 10 to 395 +/- 12
      beats/min) with shorter duration (for 20 min) than in DOCA. This significant
      depressor and bradycardic response to Ca2+ i.c.v. observed in DOCA was dose
      dependent at Ca2+ concentrations between 65.2 and 130.4 mM. In DOCA, high Ca2+
      i.c.v. reduced the plasma noradrenaline (Nad) concentration significantly (479 +/
      81 to 319 +/- 62 pg/ml, p < 0.05). These results suggest that central Ca2+ plays
      a more important role in regulating sympathetic nerve activity and BP in salt
      dependent than in renin-dependent experimental hypertension.

PMID- 9234657
TI  - Effects of a new cardiotonic phosphodiesterase III inhibitor, olprinone, on
      cardiohemodynamics and plasma hormones in conscious pigs with heart failure.
AB  - We examined the effects of a novel phosphodiesterase III inhibitor, olprinone, on
      the cardiohemodynamics and plasma hormones in conscious pigs with pacing-induced
      heart failure. After pacing for 5-10 days, cardiac output (CO) decreased from
      2.25 +/- 0.17 to 1.67 +/- 0.13 L/min (n = 8, p < 0.01) and stroke volume (SV)
      decreased from 20.1 +/- 2.1 to 12.0 +/- 1.6 ml (n = 8, p < 0.01), whereas left
      arterial pressure (LAP) increased from 2.8 +/- 1.2 to 16.7 -/+ 0.9 mm Hg (n = 7,
      p < 0.001) and systemic vascular resistance (SVR) increased from 38.7 +/- 3.5 to
      49.8 +/- 4.2 mm Hg/L/min (n = 8, p < 0.01). Sequential intravenous infusions of
      0.03, 0.3, and 3.0 microg/kg/min of olprinone at 30-min intervals to eight pigs
      caused dose-dependent increases in the decreased CO, SV, and maximal rate of rise
      in left ventricular pressure (LV dP/dt(max)) and decreased the elevated LAP and
      SVR. Olprinone at 3.0 microg/kg/min maximally increased CO, SV, and LV dP/dt(max)
      by 40.0 +/- 10.8% (p < 0.05 vs. vehicle), 25.6 +/- 6.9% (p < 0.05), and 43.9 +/-
      11.2% (p < 0.01), respectively, and brought about a slight increase in heart rate
      and decreases in LAP and SVR, by 35.9 +/- 7.3% (p < 0.001) and 27.9 +/- 4.8% (p <
      0.01), respectively. Olprinone did not affect the rate-pressure product. In
      addition, olprinone produced significant decreases in the plasma levels of atrial
      natriuretic peptide and cyclic guanosine monophosphate, with no changes in the
      plasma levels of cyclic adenosine monophosphate and catecholamines or plasma
      renin activity. These findings indicate that the short-term intravenous infusions
      of olprinone ameliorated the decreased left ventricular function without
      affecting myocardial oxygen consumption or the sympathetic nervous system in
      conscious pigs with heart failure.

PMID- 9234658
TI  - Heterogeneity in the vasorelaxing effect of nicorandil on dog epicardial coronary
      arteries: comparison with other NO donors.
AB  - The relaxation responses to nicorandil, nitroglycerin (NTG), and cromakalim were
      compared in isolated dog large (>1.5 mm inside diameter) and small (<0.3 mm
      inside diameter) epicardial coronary arteries. Nicorandil and NTG produced more
      potent relaxing effects in large coronary arteries. In contrast, cromakalim
      produced greater relaxation in small arteries. No significant differences were
      observed in the nitric oxide (NO)-induced response after treatment with
      superoxide dismutase. The responses to 8-bromo-cyclic guanosine monophosphate
      (cGMP), SIN-1, and atrial natriuretic peptide did not differ in arteries of
      different sizes. Treatment with L-cysteine had no significant effect on the
      relaxation responses to NTG in both large and small coronary arteries.
      Oxyhemoglobin and glibenclamide inhibited relaxation induced by nicorandil in
      large and small coronary arteries. Oxyhemoglobin had a greater suppressive effect
      on the response to nicorandil in large coronary arteries than in small coronary
      arteries. Methylene blue inhibited the response to nicorandil in large coronary
      arteries. These findings suggest that nicorandil behaves predominantly as a
      nitrate in large epicardial coronary arteries rather than small epicardial
      arteries and that this difference between large and small coronary arteries with
      regard to the nitrate action of nicorandil may be the result of a pathway in
      which nicorandil is converted to NO.

PMID- 9234659
TI  - Coronary arterial hyperreactivity and mesenteric arterial hyporeactivity after
      myocardial infarction in the rat.
AB  - After myocardial infarction, several neurohumoral systems become activated to
      maintain systemic perfusion pressure. We evaluated whether this leads to
      alterations of wall structure and contractile reactivity in the thoracic aorta,
      coronary septal artery, and mesenteric resistance arteries. In male Wistar rats,
      myocardial infarction (MI) was induced by permanent ligation of the left coronary
      artery. At 5 weeks after MI or sham operation, vessel segments were isolated,
      chemically sympathectomized, and mounted in a myograph for recording of isometric
      force development. Contractile reactivity to high potassium, norepinephrine,
      phenylephrine, serotonin, and Arg-vasopressin was determined. At the end of the
      experiments, vessels were fixed for morphometric analysis (cross-sectional area,
      media thickness, radius, and wall-to-lumen ratio). At 5 weeks after myocardial
      infarction, no alterations of contractile reactivity or wall structure were
      observed in the thoracic aorta of MI rats. In mesenteric resistance arteries, a
      nonselective reduction of maximal active wall tension and of active wall stress
      in response to vasoconstrictors was observed, whereas vessel wall structure and
      sensitivity to stimuli were not modified. On the other hand, coronary septal
      arteries displayed hyperreactivity to all strong contractile stimuli. These
      observations demonstrate a heterogeneity of arterial reactivity changes at 5
      weeks after MI in the rat: (a) no alterations in thoracic aorta, (b)
      hyporeactivity of mesenteric resistance arteries despite maintenance of media
      mass, and (c) hyperreactivity of coronary vessels obtained from the hypertrophic
      remnant myocardium. This could result from the complex regional hemodynamic and
      neurohumoral changes associated with heart failure and may contribute to the
      further deterioration of cardiovascular function in this setting.

PMID- 9234660
TI  - Hemodynamic effects of isoprostanes (8-iso-prostaglandin F2alpha and E2) in
      isolated guinea pig hearts.
AB  - Isoprostanes are a family of prostaglandin-related compounds formed from
      arachidonic acid in a cyclooxygenase-independent manner as products of free
      radical-initiated lipid peroxidation. To elucidate the biological activity of the
      F2-and E2-isoprostanes, 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and 8-iso
      prostaglandin E2 (8-iso-PGE2), we measured hemodynamic effects in isolated
      perfused guinea pig hearts after cumulative administration (3 x 10(-9)-10(-5) M)
      of these compounds into the coronary system. Coronary flow (CF), left ventricular
      pressure (LVP), maximal rate of pressure development (dP/dt(max)), and heart rate
      were determined continuously. Furthermore, net release of lactate into the
      coronary venous effluent and myocardial pyruvate consumption were measured.
      Comparative studies were performed with the known potent vasoconstrictor
      endothelin-1 (6 x 10(-12)-2 x 10(-9) M). Both 8-iso-PGF2alpha and 8-iso-PGE2
      induced concentration-dependent decreases in CF, which declined maximally to
      approximately 50% of the baseline level. The potencies of the two compounds were
      almost identical. Alterations in CF were associated in both groups with parallel
      reductions of LVP and dP/dt(max); heart rate was not influenced. Furthermore, the
      diminished CF caused enhanced lactate release and a reduced pyruvate consumption.
      All isoprostane-induced hemodynamic changes were prevented by coapplication of
      the thromboxane A2-receptor antagonist SQ 29548 (1 microM). Endothelin-1 caused
      CF reductions associated with loss of myocardial contractility, just like the
      isoprostanes. We conclude that in isolated guinea pig hearts, 8-iso-PGF2alpha and
      8-iso-PGE2 are potent vasoconstrictors. The action appears to be mediated by SQ
      29548-responsive thromboxane receptors. The accompanying loss of contractility is
      a secondary phenomenon, elicited by infringed oxygen supply.

PMID- 9234661
TI  - Effects of magnesium sulfate on the canine cardiovascular system complicating
      astemizole overdose.
AB  - Polymorphic ventricular arrhythmias induced by astemizole overdose have been
      reported to be successfully managed with intravenous magnesium sulfate. This
      study was designed to assess the effects of magnesium sulfate on the
      cardiovascular system, complicating astemizole overdose, the better to understand
      the therapeutic utility and undesirable effects of magnesium sulfate. Beagle dogs
      were anesthetized with halothane inhalation (n = 6). Monophasic action potential
      of the right ventricle, electrocardiogram, and systemic and left ventricular
      pressure were continuously monitored. Cardiac output was measured by a
      thermodilution method. Effective refractory period of the right ventricle was
      assessed by programmed electrical stimulation. An intentionally high dose of
      astemizole (3 mg/kg, i.v.) prolonged the repolarization and refractory period,
      while it decreased the sinus automaticity, ventricular contraction, and
      conduction. A canine antiarrhythmic dose of magnesium sulfate (100 mg/kg, i.v.)
      was additionally injected 1 h after i.v. astemizole. Magnesium sulfate increased
      the atrioventricular conduction time, electrical vulnerability, and preload of
      the left ventricle, while it decreased the blood pressure and cardiac output,
      besides the effects similar to those observed after i.v. astemizole. The plasma
      concentration of astemizole was at least 10 times higher than its therapeutic
      concentration during the experimental period. Magnesium sulfate could be expected
      to act as a calcium channel blocker during astemizole overdose; however, it may
      not antagonize the proarrhythmic effects of astemizole.

PMID- 9234662
TI  - Identification of histamine H3 receptors in the tail artery from normotensive and
      spontaneously hypertensive rats.
AB  - We examined the possible existence of prejunctional histamine H3 receptors on
      sympathetic nerve fibers innervating rat tail artery. The stimulation-evoked
      tritium outflow from isolated vessels preincubated with [3H]-noradrenaline and
      perfused/superfused in the presence of the alpha2-adrenoceptor antagonist
      rauwolscine, 3 microM, was inhibited by histamine 10 microM (by 8%) and the H3
      agonists R-(-)-alpha-methylhistamine, 10 microM (by 18%), and imetit, 0.1-10
      microM (by < or =20%). The inhibitory effect of imetit, which did not occur in
      the absence of rauwolscine, was counteracted by thioperamide, 1 microM. In the
      presence of rauwolscine, 3 microM, the inhibitory effect of imetit also occurred
      when the current strength or the Ca2+ concentration in the medium was reduced to
      compensate for the increase in tritium overflow elicited by rauwolscine,
      indicating that the inhibitory action of imetit is not associated with the
      increase in noradrenaline release produced by rauwolscine. In spontaneously
      hypertensive rats (SHRs), imetit also inhibited the overflow of tritium. This
      inhibitory effect was comparable to that observed in Wistar-Kyoto (WKY) rats and
      indicates that the sympathetic nerves of the rat tail artery in SHRs, like those
      in normotensive rats, are endowed with prejunctional histamine H3 receptors.

PMID- 9234663
TI  - Hemodynamic changes, plasma catecholamine responses, and echocardiographically
      detected contractile reserve during two different dobutamine-infusion protocols.
AB  - We studied hemodynamic changes, catecholamine responses, and the occurrence of
      improved wall thickening by echocardiography during two different dobutamine
      infusion protocols. Forty-three patients were studied by using a stepwise
      incremental dobutamine dose-infusion protocol (10-40 microg/kg/min, 3-min
      intervals); a subgroup of 11 patients also underwent a continuous dobutamine
      infusion protocol (10 microg/kg/min for 12 min) in random order. No patient used
      beta-blockers. At 3-min intervals, blood pressure, heart rate, and plasma
      concentrations of dobutamine, epinephrine, and norepinephrine were measured. The
      echocardiographic improvement of wall thickening was analyzed only in paired
      protocols by visual assessment in left ventricular regions with normal wall
      motion at rest. The mean heart rate increased in the continuous and stepwise
      protocols from 73 to 99 and 74 to 132 beats/min. There was no significant change
      in blood pressure response between the two protocols. The mean plasma dobutamine
      concentrations during the continuous and stepwise protocols at 0, 3, 6, 9, and 12
      min were 0/0; 31/38; 80/203; 106/448; and 120/692 ng/ml, respectively. In each
      patient, a response curve was constructed for the plasma dobutamine concentration
      versus heart rate. The heart rate increment and dobutamine concentration at which
      wall thickening was detected were similar with both protocols (14 +/- 5 vs. 12 +/
      7 beats/min) and (80 +/- 40 vs. 92 +/- 48 ng/ml; mean +/- SD). Wall thickening
      was noted in two of 11 patients between 0 and 3 min and 11 of 11 patients between
      3 and 6 min in both protocols. Catecholamine responses during the continuous and
      stepwise protocols were epinephrine, 23 versus 28/28 versus 36, and
      norepinephrine 301 versus 323/347 versus 519. Only norepinephrine plasma
      concentrations increased significantly during the stepwise protocol. A 6-min
      dobutamine infusion was sufficient during both protocols to reach an adequate
      plasma dobutamine concentration, which induced a detectable increase of wall
      thickening in all patients. There is a significant differences between the two
      protocols with regard to the plasma catecholamine changes, so some of the
      hemodynamic effects during the stepwise dobutamine-infusion protocol may be
      mediated through release of endogenous catecholamines.

PMID- 9234664
TI  - KRN4884, a novel K channel opener: antihypertensive effects in conscious renal
      hypertensive dogs.
AB  - We examined the antihypertensive effects of KRN4884, 5-amino-N-[2-(2
      chlorophenyl)ethyl]-N'-cyano-3-pyridinecarbocamidine+ ++, in normotensive dogs, a
      high-renin model acute renal hypertensive dog (RHD), and a low-renin model
      chronic RHD in the conscious state, compared with levcromakalim and nilvadipine.
      KRN4884 decreased mean blood pressure (MBP) at a dose of 0.1 mg/kg p.o. in
      normotensive dogs and both RHDs. The decrease in MBP was greater in both RHDs
      than in normotensive dogs, and there were no significant differences between the
      two RHDs. A transient increase in heart rate (HR) accompanied the increase in MBP
      in all three types of dogs. In the chronic RHD, KRN4884 at doses of 0.05, 0.1,
      and 0.2 mg/kg produced a dose-dependent decrease in MBP. The antihypertensive
      effect of KRN4884 (0.1 mg/kg) was similar to those of levcromakalim (0.05 mg/kg)
      and nilvadipine (1.0 mg/kg) in magnitude and more prolonged than those of the
      compounds. The tachycardia induced by KRN4884 was similar to that induced by
      levcromakalim and was stronger than that induced by nilvadipine. In the 15-day
      repeated oral-administration study, KRN4884 (0.1 mg/kg) induced sustained
      hypotensive effects and transient increases in HR and plasma renin activity. No
      tolerance to the antihypertensive effect of KRN4884 was observed during a 15-day
      repeated dosing period. After withdrawal of KRN4884, no rebound phenomena in MBP
      and HR were observed. Neither the maximal concentration nor area under the curve
      (AUC) of KRN4884 in plasma were changed at days 1, 8, and 15. These data indicate
      that KRN4884 produces a strong and persistent antihypertensive response in both
      low-renin and high-renin models of RHD in a conscious state, which suggests that
      KRN4884 may be useful as an antihypertensive agent.

PMID- 9234665
TI  - Detection of endothelin receptors in human coronary artery vascular smooth muscle
      cells but not endothelial cells by using electron microscope autoradiography.
AB  - Endothelin A (ET(A)) and ET(B) receptors located on vascular smooth-muscle cells
      mediate potent vasoconstriction in animal and human blood vessels. Although
      vascular endothelial ET(B) receptors mediate vasodilatation through release of
      nitric oxide, prostacyclin, or an endothelium-derived hyperpolarizing factor in
      animal vessels, there is less evidence to support ET-mediated endothelium
      dependent relaxation in human arteries. We investigated the regional and
      subcellular localization of ET-receptor subtypes in human epicardial coronary
      arteries obtained from patients with congestive heart failure undergoing cardiac
      transplantation. Radioligand-binding studies revealed a predominance of the ET(A)
      receptor subtype in the coronary artery. ET(A) and ET(B) receptors were located
      in the media and in perivascular structures by using macroautoradiography.
      Specific binding in the intimal layer was low. Autoradiography at the
      ultrastructural level revealed the presence of ET(A) and ET(B) receptors on
      medial vascular smooth-muscle cell plasmalemma and plasmalemmal vesicles with a
      predominance of the ET(A) subtype. ET receptors were not detected in either
      luminal endothelial cells of the coronary arteries or endothelial cells lining
      small adventitial blood vessels. This study is the first to identify the
      subcellular localization of ET receptors in human coronary artery vascular smooth
      muscle cells. These receptors probably mediate the well-established
      vasoconstrictor response to ET-1. The inability to detect ET receptors on
      endothelial cells suggests a minor role for endothelial cells in ET-mediated
      vasodilatation of the coronary vasculature.

PMID- 9234666
TI  - Influence of cytochrome P-450 inhibitors on endothelium-dependent nitro-L
      arginine-resistant relaxation and cromakalim-induced relaxation in rat mesenteric
      arteries.
AB  - In several blood vessels, endothelium-dependent vasorelaxation is in part
      mediated by an endothelium-derived hyperpolarizing factor (EDHF), the nature of
      which is as yet unknown. However, some evidence suggests that EDHF might be a
      cytochrome P-450-dependent monooxygenase metabolite of arachidonic acid. By using
      isometric tension measurements on rat main mesenteric arteries, the influence of
      four structurally and mechanistically different cytochrome P-450 inhibitors
      (proadifen, miconazole, 1-amino-benzotriazole, and 17-octadecynoic acid) was
      investigated on relaxations elicited by EDHF, assessed as the nitro-L-arginine
      resistant component of acetylcholine-induced relaxation, and on relaxations
      provoked by the endothelium-independent potassium channel opener cromakalim.
      Proadifen (30 microM) inhibited the EDHF- as well as the cromakalim-induced
      relaxation, but not that elicited by nitroprusside. Also miconazole (30 microM)
      inhibited both the EDHF and the cromakalim-induced relaxation. On the other hand,
      17-octadecynoic acid (5 microM) had no influence, and 1-aminobenzotriazole (1 mM)
      even potentiated EDHF- and cromakalim-induced relaxations. We conclude that the
      EDHF, released from the rat mesenteric artery by acetylcholine, is unlikely to be
      a cytochrome P-450-dependent monooxygenase metabolite of arachidonic acid and
      that proadifen and miconazole interfere with the action of cromakalim.

PMID- 9234667
TI  - Modulation of glycerol and ethanol yields during alcoholic fermentation in
      Saccharomyces cerevisiae strains overexpressed or disrupted for GPD1 encoding
      glycerol 3-phosphate dehydrogenase.
AB  - The possibility of the diversion of carbon flux from ethanol towards glycerol in
      Saccharomyces cerevisiae during alcoholic fermentation was investigated.
      Variations in the glycerol 3-phosphate dehydrogenase (GPDH) level and similar
      trends for alcohol dehydrogenase (ADH), pyruvate decarboxylase and glycerol-3
      phosphatase were found when low and high glycerol-forming wine yeast strains were
      compared. GPDH is thus a limiting enzyme for glycerol production. Wine yeast
      strains with modulated GPD1 (encoding one of the two GPDH isoenzymes) expression
      were constructed and characterized during fermentation on glucose-rich medium.
      Engineered strains fermented glucose with a strongly modified [glycerol] :
      [ethanol] ratio. gpd1delta mutants exhibited a 50% decrease in glycerol
      production and increased ethanol yield. Overexpression of GPD1 on synthetic must
      (200 g/l glucose) resulted in a substantial increase in glycerol production ( x
      4) at the expense of ethanol. Acetaldehyde accumulated through the competitive
      regeneration of NADH via GPDH. Accumulation of by-products such as pyruvate,
      acetate, acetoin, 2,3 butane-diol and succinate was observed, with a marked
      increase in acetoin production.

PMID- 9234668
TI  - Characterization of CHS4 (CAL2), a gene of Saccharomyces cerevisiae involved in
      chitin biosynthesis and allelic to SKT5 and CSD4.
AB  - We have cloned CHS4, a gene that complements the resistance to Calcofluor of the
      Saccharomyces cerevisiae cal2 mutant. We show that CHS4 is allelic to the
      previously described SKT5 and CSD4 genes. CHS4 encodes a 696 amino acids protein
      with no potential transmembrane domain. chs4-null mutants are resistant to
      Calcofluor white and exhibit a considerable reduction in cell wall chitin and in
      chitin synthase III (CSIII) activity. Biochemical characterization of chitin
      synthase III from these null mutants indicates that the defect is due to a
      reduced V(max) of the enzyme. This defect can be overcome in vitro by trypsin
      treatment of the membrane preparations. Chs4p does not act as a transcriptional
      or translational regulator of CHS3, the gene coding for the catalytic subunit of
      CSIII activity, and we therefore propose that Chs4p would be an essential
      component of the CSIII complex, acting as a post-translational regulator of this
      activity. In addition to the chitin defect, the chs4 mutant shows a severe defect
      in mating.

PMID- 9234669
TI  - Characterization of two new genes down-regulated by alpha-factor.
AB  - To detect genes directly down-regulated by alpha-factor, 55,000 plaque-forming
      units of a Saccharomyces cerevisiae lambda gt10 gene bank were differentially
      screened with cDNA of cells treated with alpha-factor for 20 min. Two new genes
      were detected in this way, called alpha0.5 and alpha0.6. The former is
      transiently down-regulated by alpha-factor; it is very highly transcribed in late
      exponential-phase cells. The gene, located on the right arm of chromosome XIII,
      codes for a 59 amino-acid protein with a signal peptide. The protein has been
      shown with an antibody to be present in the membrane fraction. The gene has also
      been cloned as HOR7 (hyperosmolarity-responsive protein; Hirayama et al., 1995).
      No other homologous sequences have been detected in the yeast genome. alpha0.6,
      located on the right arm of chromosome XII, corresponds to the open reading frame
      YLR110c; it codes for a 133 amino-acid protein containing a signal peptide. Its
      derived amino-acid sequence is homologous to the N-terminal half of the SED1 gene
      product. SED1, when overexpressed, is able to suppress a defect in the HDEL
      receptor coded for by the ERD2 gene (Hardwick and Pelham, 1994); however,
      alpha0.6 is not able to do so. The disruption of alpha0.5 or alpha0.6 does not
      lead to a special phenotype.

PMID- 9234670
TI  - Isolation of three contiguous genes, ACR1, ACR2 and ACR3, involved in resistance
      to arsenic compounds in the yeast Saccharomyces cerevisiae.
AB  - A 4.2 kb region from Saccharomyces cerevisiae chromosome XVI was isolated as a
      yeast fragment conferring resistance to 7 mM-sodium arsenite (NaAsO2), when put
      on a multicopy plasmid. Homology searches revealed a cluster of three new open
      reading frames named ACR1, ACR2 and ACR3. The hypothetical product of the ACR1
      gene is similar to the transcriptional regulatory proteins, encoded by YAP1, and
      YAP2 genes from S. cerevisiae. Disruption of the ACR1 gene conduces to an
      arsenite and arsenate hypersensitivity phenotype. The ACR2 gene is indispensable
      for arsenate but not for arsenite resistance. The hypothetical product of the
      ACR3 gene shows high similarity to the hypothetical membrane protein encoded by
      Bacillus subtilis ORF1 of the skin element and weak similarity to the ArsB
      membrane protein of the Staphylococcus aureus arsenical-resistance operon.
      Overexpression of the ACR3 gene confers an arsenite- but not an arsenate
      resistance phenotype. The presence of ACR3 together with ACR2 on a multicopy
      plasmid expands the resistance phenotype into arsenate. These findings suggest
      that all three novel genes: ACR1, ACR2 and ACR3 are involved in the arsenical
      resistance phenomenon in S. cerevisiae.

PMID- 9234671
TI  - Cloning, sequencing and expression of a full-length cDNA copy of the M1 double
      stranded RNA virus from the yeast, Saccharomyces cerevisiae.
AB  - Strains of the budding yeast, Saccharomyces cerevisiae, may contain one or more
      cytoplasmic viruses with double-stranded RNA (dsRNA) genomes. The killer
      phenomenon in yeast, in which one cell secretes a killer toxin that is lethal to
      another cell, is dependent upon the presence of the L-A and M1 dsRNA viruses. The
      L-A viral genome encodes proteins for the viral capsid, and for synthesis and
      encapsidation of single-stranded RNA replication cycle intermediates. The M1
      virus depends upon the L-A-encoded proteins for its capsid and for the
      replication of its killer-toxin-encoding genome. A full-length cDNA clone of an M
      genome has been made from a single dsRNA molecule and shown to encode functional
      killer and killer-immunity functions. The sequence of the clone indicates minor
      differences from previously published sequences of parts of the M1 genome and of
      the complete genome of S14 (an internal deletion derivative of M1) but no
      unreported amino acid variants and no changes in putative secondary structures of
      the single-stranded RNA. A 118-nucleotide contiguous segment of the M1 genome has
      not previously been reported; 92 of those nucleotides comprise a segment of A
      nucleotides in the AU-rich bubble that follows the toxin-encoding reading frame.

PMID- 9234672
TI  - A set of vectors with a tetracycline-regulatable promoter system for modulated
      gene expression in Saccharomyces cerevisiae.
AB  - A set of Saccharomyces cerevisiae expression vectors has been developed in which
      transcription is driven by a hybrid tetO-CYC1 promoter through the action of a
      tetR-VP16 (tTA) activator. Expression from the promoter is regulated by
      tetracycline or derivatives. Various modalities of promoter and activator are
      used in order to achieve different levels of maximal expression. In the presence
      of antibiotic in the growth medium at concentrations that do not affect cell
      growth, expression from the tetO promoter is negligible, and upon antibiotic
      removal induction ratios of up to 1000-fold are observed with a lacZ reporter
      system. With the strongest system, overexpression levels comparable with those
      observed with GAL1-driven promoters are reached. For each particular promoter/tTA
      combination, expression can be modulated by changing the tetracycline
      concentration in the growth medium. These vectors may be useful for the study of
      the function of essential genes in yeast, as well as for phenotypic analysis of
      genes in overexpression conditions, without restrictions imposed by growth medium
      composition.

PMID- 9234673
TI  - Sequence analysis of the 33 kb long region between ORC5 and SUI1 from the left
      arm of chromosome XIV from Saccharomyces cerevisiae.
AB  - We have determined the nucleotide sequence of a chromosomal region of 33,016 bp
      located on the left arm of chromosome XIV from budding yeast between the ORC5 and
      the SUI1 gene. Subsequent sequence analysis revealed the presence of 18 non
      overlapping open reading frames (ORFs) including eight previously identified and
      sequenced genes (ORC5, ATX1, SIP3, NRD1, RAD50, MPA43, RPA49 and SUI1). Three
      other ORFs (YNL256w, YNL255c and YNL247w) code for putative proteins with
      significant homology to proteins from other organisms, while 4 ORFs exhibit only
      weak homology to known proteins. Three ORFs have no homology with sequences in
      the databases.

PMID- 9234674
TI  - The characterization of two new clusters of duplicated genes suggests a 'Lego'
      organization of the yeast Saccharomyces cerevisiae chromosomes.
AB  - The systematic sequencing of 42,485 bp of yeast chromosome VII (nucleotides
      377948 to 420432) has revealed the presence of 27 putative open reading frames
      (ORFs) coding for proteins of at least 100 amino acids. The degree of redundancy
      observed is elevated since five of the 27 ORFs are duplications of a previously
      identified gene. These duplicated copies may be classified in two types of
      cluster organization. The first type includes genes sharing a significant level
      of identity in the amino acid sequences of their predicted protein product. They
      are recovered on two different chromosomes, transcribed in the same orientation
      and the distance between them is conserved. The second type of cluster is based
      on one gene unit tandemly repeated. This duplication is itself repeated elsewhere
      in the genome. The level of nucleic acid identity is high within the coding
      sequence and the non-coding region between the two repeats. In addition, the
      basic gene unit is recovered many times in the genome and is a component of a
      multigene family of unknown function. These organizations in clusters of genes
      suggest a 'Lego organization' of the yeast chromosomes, as recently proposed for
      the genome of plants (Moore, 1995). The sequence is deposited in the Yeast Genome
      Databank under Accession Number from Z72562 to Z72586.

PMID- 9234675
TI  - Isolation and characterization of the Candida albicans PFY1 gene for profilin.
AB  - We have isolated the Candida albicans gene for profilin, PFY1. Degenerate
      oligonucleotide primers based on regions of high homology were utilized to obtain
      a polymerase chain reaction-amplified copy of the gene. This was then used as a
      probe to isolate the gene from a C. albicans genomic library. Our studies
      indicate that the full-length gene is unstable in Escherichia coli. Several
      clones were sequenced, and the predicted amino acid sequence demonstrated
      homology with profilin proteins from other organisms, most notably Saccharomyces
      cerevisiae. Northern analysis revealed that the gene is expressed in C. albicans.
      Attempts to express the gene in S. cerevisiae cells were unsuccessful until the
      C. albicans promoter was replaced with an S. cerevisiae promoter. Functional
      complementation of the gene was demonstrated in S. cerevisiae profilin-requiring
      cells. Antibodies raised to isolated C. albicans profilin protein recognized a
      protein of the predicted molecular weight when the gene was expressed in S.
      cerevisiae cells.

PMID- 9234677
TI  - Premature 3'-end formation of CBP1 mRNA results in the downregulation of
      cytochrome b mRNA during the induction of respiration in Saccharomyces
      cerevisiae.
AB  - The yeast mitochondrial genome encodes only seven major components of the
      respiratory chain and ATP synthase; more than 200 other mitochondrial proteins
      are encoded by nuclear genes. Thus, assembly of functional mitochondria requires
      coordinate expression of nuclear and mitochondrial genes. One example of
      coordinate regulation is the stabilization of mitochondrial COB (cytochrome b)
      mRNA by Cbp1, the product of the nuclear gene CBP1 (cytochrome b processing).
      CBP1 produces two types of transcripts with different 3' ends: full-length 2.2-kb
      transcripts and 1.2-kb transcripts truncated within the coding sequence of Cbp1.
      Upon induction of respiration, the steady-state level of the long transcripts
      decreases while that of the short transcripts increases reciprocally, an
      unexpected result since the product of the long transcripts is required for COB
      mRNA stability and thus for respiration. Here we have tested the hypothesis that
      the short transcripts, or proteins translated from the short transcripts, are
      also required for respiration. A protein translated from the short transcripts
      was not detected by Western analysis, although polysome gradient fractions were
      shown to contain both long and short CBP1 transcripts. A mutant strain in which
      production of the short transcripts was abolished showed wild-type growth
      properties, indicating that the short transcripts are not required for
      respiration. Due to mutation of the carbon source-responsive element, the long
      transcript level in the mutant strain did not decrease during induction of
      respiration. The mutant strain had increased levels of COB RNA, suggestive that
      production of short CBP1 transcripts is a mechanism for downregulation of the
      levels of long CBP1 transcripts, Cbp1, and COB mRNA during the induction of
      respiration.

PMID- 9234678
TI  - Protein kinase A-dependent phosphorylation modulates DNA-binding activity of
      hepatocyte nuclear factor 4.
AB  - Hepatocyte nuclear factor 4 (HNF4), a liver-enriched transcription factor of the
      nuclear receptor superfamily, is critical for development and liver-specific gene
      expression. Here, we demonstrate that its DNA-binding activity is modulated
      posttranslationally by phosphorylation in vivo, ex vivo, and in vitro. In vivo,
      HNF4 DNA-binding activity is reduced by fasting and by inducers of intracellular
      cyclic AMP (cAMP) accumulation. A consensus protein kinase A (PKA)
      phosphorylation site located within the A box of its DNA-binding domain has been
      identified, and its role in phosphorylation-dependent inhibition of HNF4 DNA
      binding activity has been investigated. Mutants of HNF4 in which two potentially
      phosphorylatable serines have been replaced by either neutral or charged amino
      acids were able to bind DNA in vitro with affinity similar to that of the wild
      type protein. However, phosphorylation by PKA strongly repressed the binding
      affinity of the wild-type factor but not that of HNF4 mutants. Accordingly, in
      transfection assays, expression vectors for the mutated HNF4 proteins activated
      transcription more efficiently than that for the wild-type protein-when
      cotransfected with the PKA catalytic subunit expression vector. Therefore, HNF4
      is a direct target of PKA which might be involved in the transcriptional
      inhibition of liver genes by cAMP inducers.

PMID- 9234679
TI  - A conserved tissue-specific structure at a human T-cell receptor beta-chain core
      promoter.
AB  - The T-cell receptor (TCR) beta-chain promoters have been characterized as
      nonstructured basal promoters that carry a single conserved ubiquitous cyclic AMP
      responsive element. Our investigation of the human TCR beta gene uncovers a
      surprisingly complex and tissue-specific structure at the TCR Vbeta 8.1 promoter.
      The core of the promoter (positions -42 to +11) is recognized by the lymphoid
      cell-specific transcription factors Ets-1, LEF1, and AML1 as well as by CREB/ATF
      1, as is demonstrated in gel shift and footprinting experiments. With the
      exception of LEF1, these factors activate transcription in T cells. Binding sites
      at the core region show little conservation with consensus sites. Nonetheless,
      CREB, Ets-1, and AML1 bind and activate cooperatively and very efficiently
      through the nonconsensus binding sites at the core promoter region. Moderate
      ubiquitous activation is further induced by CREB/ATF and Sp1 factors through
      proximal upstream elements. The tissue-specific core promoter structure is
      apparently conserved in other T-cell-specifically expressed genes such as the CD4
      gene. Our observations suggest that both the enhancer and the promoter have a
      complex tissue-specific structure whose functional interplay potentiates T-cell
      specific transcription.

PMID- 9234680
TI  - Mechanism of repression of RNA polymerase I transcription by the retinoblastoma
      protein.
AB  - The retinoblastoma susceptibility gene product pRb restricts cellular
      proliferation by affecting gene expression by all three classes of nuclear RNA
      polymerases. To elucidate the molecular mechanisms underlying pRb-mediated
      repression of ribosomal DNA (rDNA) transcription by RNA polymerase I, we have
      analyzed the effect of pRb in a reconstituted transcription system. We
      demonstrate that pRb, but not the related protein p107, acts as a transcriptional
      repressor by interfering with the assembly of transcription initiation complexes.
      The HMG box-containing transcription factor UBF is the main target for pRb
      induced transcriptional repression. UBF and pRb form in vitro complexes involving
      the C-terminal part of pRb and HMG boxes 1 and 2 of UBF. We show that the
      interactions between UBF and TIF-IB and between UBF and RNA polymerase I,
      respectively, are not perturbed by pRb. However, the DNA binding activity of UBF
      to both synthetic cruciform DNA and the rDNA promoter is severely impaired in the
      presence of pRb. These studies reveal another mechanism by which pRb suppresses
      cell proliferation, namely, by direct inhibition of cellular rRNA synthesis.

PMID- 9234681
TI  - C/EBP factor suppression of inhibition of type II secreted phospholipase A2
      promoter in HepG2 cells: possible role of single-strand binding proteins.
AB  - We previously reported that the type II secreted phospholipase A2 (sPLA2)
      promoter from positions (-326 to +20) ([-326;+20] promoter) is negatively
      regulated by two adjacent regulatory elements, C (-210 to -176) and D (-247 to 
      210). This study examines in greater detail the way in which this negative
      regulation operates. Successive 5' deletions of the [-326;+20] type II sPLA2
      promoter indicated that the region upstream of position -195 inhibits the
      transcription activity sixfold in HepG2 cells but not in HeLa cells. Although the
      whole [-326;-176] region decreased the activity of a heterologous thymidine
      kinase promoter, this effect was orientation and position sensitive. C/EBP beta,
      C/EBP alpha, and C/EBP delta, which bind to element C, prevented the inhibition
      of promoter activity. Electrophoretic mobility shift experiments identified the
      binding of NF1-like proteins to the [-225;-218] site, which overlaps an insulin
      response-like sequence, 5'-TGTTTTG-3'. This sequence bound a factor which also
      recognized the promoters of the apolipoproteins C-III and A-II. Substitutions
      preventing the binding of this factor or the NF1-like proteins did not increase
      the transcription activity, but substitution in the [-217;-204] sequence blocked
      the transcription inhibition. This sequence did not bind any double-strand
      binding factor, but its antisense strand is critical for the binding of single
      strand binding proteins to the [-232;-191] region. We therefore suggest that
      these single-strand binding proteins are involved in the inhibitory mechanism.

PMID- 9234682
TI  - Efficient repression of endogenous major histocompatibility complex class II
      expression through dominant negative CIITA mutants isolated by a functional
      selection strategy.
AB  - Major histocompatibility complex class II (MHC-II) molecules present peptide
      antigens to CD4-positive T cells and are of critical importance for the immune
      response. The MHC-II transactivator CIITA is essential for all aspects of MHC-II
      gene expression examined so far and thus constitutes a master regulator of MHC-II
      expression. In this study, we generated and analyzed mutant CIITA molecules which
      are able to suppress endogenous MHC-II expression in a dominant negative manner
      for both constitutive and inducible MHC-II expression. Dominant negative CIITA
      mutants were generated via specific restriction sites and by functional selection
      from a library of random N-terminal CIITA deletions. This functional selection
      strategy was very effective, leading to strong dominant negative CIITA mutants in
      which the N-terminal acidic and proline/serine/threonine-rich regions were
      completely deleted. Dominant negative activity is dependent on an intact C
      terminus. Efficient repression of endogenous MHC-II mRNA levels was quantified by
      RNase protection analysis. The quantitative effects of various dominant negative
      CIITA mutants on mRNA expression levels of the different MHC-II isotypes are very
      similar. The optimized dominant negative CIITA mutants isolated by functional
      selection should be useful for in vivo repression of MHC-II expression.

PMID- 9234683
TI  - tau4/tau c/AF-2 of the thyroid hormone receptor relieves silencing of the
      retinoic acid receptor silencer core independent of both tau4 activation function
      and full dissociation of corepressors.
AB  - Members of the thyroid hormone (TR)-retinoic acid receptor (RAR) subfamily of
      nuclear hormone receptors silence gene expression in the absence of hormone.
      Addition of cognate ligands leads to dissociation of corepressors, association of
      coactivators, and transcriptional activation. Here, we used the hRAR alpha
      silencer core, which encompasses the ligand binding domain, including receptor
      regions D and E of RAR alpha without the activation function called tau4/tau c/AF
      2 and without the F region, to analyze the mechanisms by which transcriptional
      silencing is relieved. Although the RAR silencer core is able to bind ligand, it
      acts as a constitutive transcriptional silencer. We have fused various small
      activation domains to the C terminus of the silencer core and analyzed hormone
      dependent changes in receptor function. We show that nine amino acids derived
      from the hTRbeta are sufficient to transform the RAR silencer core into a hormone
      dependent activator. Lengthening the linker between the silencer core and these
      nine amino acids is not critical for mediating ligand-induced relief of silencing
      and activation. In addition, we show that a transactivation function at the C
      terminus is not required for relief of silencing by the hormone, but it is
      required for transcriptional activation. Furthermore, we created functional
      silencer fusions which lose their repressive function upon addition of hormone,
      although the corepressors SMRT and N-CoR remain attached to the receptor.

PMID- 9234685
TI  - A family of ammonium transporters in Saccharomyces cerevisiae.
AB  - Ammonium is a nitrogen source supporting growth of yeast cells at an optimal
      rate. We recently reported the first characterization of an NH4+ transport
      protein (Mep1p) in Saccharomyces cerevisiae. Here we describe the
      characterization of two additional NH4+ transporters, Mep2p and Mep3p, both of
      which are highly similar to Mep1p. The Mep2 protein displays the highest affinity
      for NH4+ (Km, 1 to 2 microM), followed closely by Mep1p (Km, 5 to 10 microM) and
      finally by Mep3p, whose affinity is much lower (Km, approximately 1.4 to 2.1 mM).
      A strain lacking all three MEP genes cannot grow on media containing less than 5
      mM NH4+ as the sole nitrogen source, while the presence of individual NH4+
      transporters enables growth on these media. Yet, the three Mep proteins are not
      essential for growth on NH4+ at high concentrations (>20 mM). Feeding experiments
      further indicate that the Mep transporters are also required to retain NH4+
      inside cells during growth on at least some nitrogen sources other than NH4+. The
      MEP genes are subject to nitrogen control. In the presence of a good nitrogen
      source, all three MEP genes are repressed. On a poor nitrogen source, MEP2
      expression is much higher than MEP1 and MEP3 expression. High-level MEP2
      transcription requires at least one of the two GATA family factors Gln3p and
      Nil1p, which are involved in transcriptional activation of many other nitrogen
      regulated genes. In contrast, expression of either MEP1 or MEP3 requires only
      Gln3p and is unexpectedly down-regulated in a Nil1p-dependent manner. Analysis of
      databases suggests that families of NH4+ transporters exist in other organisms as
      well.

PMID- 9234684
TI  - Triple synergism of human T-lymphotropic virus type 1-encoded tax, GATA-binding
      protein, and AP-1 is required for constitutive expression of the interleukin-5
      gene in adult T-cell leukemia cells.
AB  - Accumulated evidence demonstrates that adult T-cell leukemia (ATL) is frequently
      associated with eosinophilia, and human T-lymphotropic virus type 1 (HTLV-1)
      infected cells frequently express interleukin-5 (IL-5). However, the molecular
      mechanism of constitutive IL-5 expression in HTLV-1-infected cells remains
      unclear. To clarify the mechanism of aberrant IL-5 expression in HTLV-1-infected
      cells, we investigated the response of the human IL-5 promoter to the HTLV-1
      encoded protein Tax. Cotransfection experiments using Jurkat cells revealed that
      Tax is incapable of activating the IL-5 promoter by itself but that it
      synergistically transactivates the promoter with GATA-binding protein (GATA-4)
      and 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation. By introducing a
      series of mutations within the IL-5 promoter, we found that conserved lymphokine
      element 0 (CLE0) is responsible for mediating the signal induced by Tax-TPA. A
      deletion construct of the promoter indicated that the -75 GATA element and CLE0
      are sufficient to mediate synergistic activation of the IL-5 promoter.
      Electrophoretic mobility shift assays using Jurkat cell nuclear extracts
      demonstrated that TPA induces a transcription factor to bind CLE0, and an
      experiment using JPX-9 cell nuclear extracts showed that Tax enhances this
      binding activity. An antibody supershift experiment revealed that this band
      consists of c-Jun and JunD. However, among the Jun family members, only c-Jun is
      able to cooperate with Tax and GATA-4 to activate the IL-5 promoter. We have
      determined the minimum factors required for IL-5 gene activation by
      reconstituting the IL-5 promoter activity in F9 cells. This is the first report
      to demonstrate the functional involvement of Tax protein in IL-5 gene regulation
      and to suggest the functional triple synergism among Tax, GATA-4, and AP-1, which
      disrupts regulated control of the gene and leads to constitutive expression of
      the IL-5 gene.

PMID- 9234686
TI  - EH domain proteins Pan1p and End3p are components of a complex that plays a dual
      role in organization of the cortical actin cytoskeleton and endocytosis in
      Saccharomyces cerevisiae.
AB  - Several proteins from diverse organisms have been shown to share a region of
      sequence homology with the mammalian epidermal growth factor receptor tyrosine
      kinase substrate Eps15. Included in this new protein family, termed EH domain
      proteins, are two yeast proteins, Pan1p and End3p. We have shown previously that
      Pan1p is required for normal organization of the actin cytoskeleton and that it
      associates with the actin patches on the cell cortex. End3p has been shown by
      others to be an important factor in the process of endocytosis. End3p is also
      known to be required for the organization of the actin cytoskeleton. Here we
      report that Pan1p and End3p act as a complex in vivo. Using the pan1-4 mutant
      which we isolated and characterized previously, the END3 gene was identified as a
      suppressor of pan1-4 when overexpressed. Suppression of the pan1-4 mutation by
      multicopy END3 required the presence of the mutant Pan1p protein.
      Coimmunoprecipitation and two-hybrid protein interaction experiments indicated
      that Pan1p and End3p associate with each other. The localization of Pan1p to the
      cortical actin cytoskeleton became weakened in the end3 mutant at the permissive
      temperature and undetectable at the restrictive temperature, suggesting that
      End3p may be important for proper localization of Pan1p to the cortical actin
      cytoskeleton. The finding that the pan1-4 mutant was defective in endocytosis as
      severely as the end3 mutant under nonpermissive conditions supports the notion
      that the association between Pan1p and End3p is of physiological relevance.
      Together with results of earlier reports, these results provide strong evidence
      suggesting that Pan1p and End3p are the components of a complex that has
      essential functions in both the organization of cell membrane-associated actin
      cytoskeleton and the process of endocytosis.

PMID- 9234687
TI  - Recruitment and phosphorylation of SH2-containing inositol phosphatase and Shc to
      the B-cell Fc gamma immunoreceptor tyrosine-based inhibition motif peptide motif.
AB  - Recently, we and others have demonstrated that negative signaling in B cells
      selectively induces the tyrosine phosphorylation of a novel inositol
      polyphosphate phosphatase, p145SHIP. In this study, we present data indicating
      that p145SHIP binds directly a phosphorylated motif, immunoreceptor tyrosine
      based inhibition motif (ITIM), present in the cytoplasmic domain of Fc
      gammaRIIB1. Using recombinant SH2 domains, we show that binding is mediated via
      the Src homology region 2 (SH2)-containing inositol phosphatase (SHIP) SH2
      domain. SHIP also bound to a phosphopeptide derived from CD22, raising the
      possibility that SHIP contributes to negative signaling by this receptor as well
      as Fc gammaRIIB1. The association of SHIP with the ITIM phosphopeptide was
      activation independent, while coassociation with Shc was activation dependent.
      Furthermore, experiments with Fc gammaRIIB1-deficient B cells demonstrated a
      genetic requirement for expression of Fc gammaRIIB1 in the induction of SHIP
      phosphorylation and its interaction with Shc. Based on these results, we propose
      a model of negative signaling in which co-cross-linking of surface immunoglobulin
      and Fc gammaRIIB1 results in sequential tyrosine phosphorylation of the ITIM,
      recruitment and phosphorylation of p145SHIP, and subsequent binding of Shc.

PMID- 9234688
TI  - The replication origin decision point is a mitogen-independent, 2-aminopurine
      sensitive, G1-phase event that precedes restriction point control.
AB  - At a distinct point during G1 phase (the origin decision point [ODP]), Chinese
      hamster ovary (CHO) cell nuclei experience a transition (origin choice) that is
      required for specific recognition of the dihydrofolate reductase (DHFR) origin
      locus by Xenopus egg extracts. We have investigated the relationship between the
      ODP and progression of CHO cells through G1 phase. Selection of the DHFR origin
      at the ODP was rapidly inhibited by treatment of early G1-phase cells with the
      protein kinase inhibitor 2-aminopurine (2-AP). Inhibition of the ODP required
      administration of 2-AP at least 3 h prior to phosphorylation of the
      retinoblastoma tumor suppressor protein (Rb) and the restriction point (R point).
      Cells deprived of either serum or isoleucine from metaphase throughout early G1
      phase acquired the capacity to replicate in Xenopus egg extract (replication
      licensing) and subsequently passed through the ODP on the same schedule as cells
      cultured in complete growth medium. After growth arrest at the R point with
      hypophosphorylated Rb protein, serum- or isoleucine-deprived cells experienced a
      gradual loss of replication licensing. However, recognition of the DHFR origin by
      Xenopus egg cytosol remained stable in growth-arrested cells until the point at
      which all nuclei had lost the capacity to initiate replication. These results
      provide evidence that the ODP requires a mitogen-independent protein kinase that
      is activated after replication licensing and prior to R-point control.

PMID- 9234689
TI  - A 5' 2-kilobase-pair region of the imprinted mouse H19 gene exhibits exclusive
      paternal methylation throughout development.
AB  - The imprinted mouse H19 gene is hypermethylated on the inactive paternal allele
      in somatic tissues and sperm. Previous observations from a limited analysis have
      suggested that methylation of a few CpG dinucleotides in the region upstream from
      the start of transcription may be the mark that confers parental identity to the
      H19 alleles. Here we exploit bisulfite mutagenesis coupled with genomic
      sequencing to derive the methylation status of 68 CpGs that reside in a 4-kb
      region 5' to the start of transcription. This method reveals a 2-kb region
      positioned between 2 and 4 kb upstream from the start of transcription that is
      strikingly differentially methylated in midgestation embryos. At least 12 of the
      cytosine residues in this region are exclusively methylated on the paternal
      allele in blastocysts. In contrast, a 350-bp promoter-proximal region is less
      differentially methylated in midgestation embryos and, like most of the genome,
      is largely devoid of methylation on both alleles in blastocysts. We also
      demonstrate exclusive expression of the maternal H19 allele in the embryos that
      exhibit paternal methylation of the upstream 2-kb region. These data suggest that
      the 2-kb differentially methylated region acts as a key regulatory domain for
      imprinted H19 expression.

PMID- 9234690
TI  - Cooperative binding interactions required for function of the Ty1 sterile
      responsive element.
AB  - The Ste12p transcription factor controls the expression of Ty1 transposable
      element insertion mutations and genes whose products are required for mating in
      Saccharomyces cerevisiae. The binding site for Ste12p is a consensus DNA sequence
      known as a pheromone response element (PRE). Upstream activating sequences (UASs)
      derived from known Ste12p-dependent genes have previously been characterized to
      require either multiple PREs or a single PRE coupled to a binding site for a
      second protein. The Ste12p-dependent UAS from Ty1, called a sterile response
      element (SRE), is of the second type and is comprised of a PRE and an adjacent
      TEA (TEF-1, Tec1, and AbaA motif) DNA consensus sequence (TCS). In this report,
      we show by UV cross-linking analysis that two proteins, Ste12p and a protein with
      an apparent size of 72 kDa, directly contact the Ty1 SRE. Other experiments show
      that Tec1p is required for formation of the Ty1 SRE protein-DNA complex and is
      physically present in the complex. These results establish a direct role for
      Tec1p in the Ty1 SRE and yet another set of combinatorial interactions that
      achieve a qualitatively distinct mode of transcriptional regulation with Ste12p.

PMID- 9234691
TI  - p21CIP1 and Cdc25A: competition between an inhibitor and an activator of cyclin
      dependent kinases.
AB  - Cdc25A, a phosphatase essential for G1-S transition, associates with,
      dephosphorylates, and activates the cell cycle kinase cyclin E-cdk2. p21CIP1 and
      p27 are cyclin-dependent kinase (cdk) inhibitors induced by growth-suppressive
      signals such as p53 and transforming growth factor beta (TGF-beta). We have
      identified a cyclin binding motif near the N terminus of Cdc25A that is similar
      to the cyclin binding Cy (or RR LFG) motif of the p21CIP1 family of cdk
      inhibitors and separate from the catalytic domain. Mutations in this motif
      disrupt the association of Cdc25A with cyclin E- or cyclin A-cdk2 in vitro and in
      vivo and selectively interfere with the dephosphorylation of cyclin E-cdk2. A
      peptide based on the Cy motif of p21 competitively disrupts the association of
      Cdc25A with cyclin-cdks and inhibits the dephosphorylation of the kinase. p21
      inhibits Cdc25A-cyclin-cdk2 association and the dephosphorylation of cdk2.
      Conversely, Cdc25A, which is itself an oncogene up-regulated by the Myc oncogene,
      associates with cyclin-cdk and protects it from inhibition by p21. Cdc25A also
      protects DNA replication in Xenopus egg extracts from inhibition by p21. These
      results describe a mechanism by which the Myc- or Cdc25A-induced oncogenic and
      p53- or TGF-beta-induced growth-suppressive pathways counterbalance each other by
      competing for cyclin-cdks.

PMID- 9234692
TI  - Positioning atypical protein kinase C isoforms in the UV-induced apoptotic
      signaling cascade.
AB  - Recent studies have documented the involvement of the atypical protein kinase C
      (aPKC) isoforms in important cellular functions such as cell proliferation and
      survival. Exposure of cells to a genotoxic stimulus that induces apoptosis, such
      as UV irradiation, leads to a profound inhibition of the atypical PKC activity in
      vivo. In this study, we addressed the relationship between this phenomenon and
      different proteins involved in the apoptotic response. We show that (i) the
      inhibition of the aPKC activity precedes UV-induced apoptosis; (ii) UV-induced
      aPKC inhibition and apoptosis are independent of p53; (iii) Bcl-2 proteins are
      potent modulators of aPKC activity; and (iv) the aPKCs are located upstream of
      the interleukin-converting enzyme-like protease system, which is required for the
      induction of apoptosis by both Par-4 (a selective aPKC inhibitor) and UV
      irradiation. We also demonstrate here that inhibition of aPKC activity leads to a
      decrease in mitogen-activated protein (MAP) kinase activity and simultaneously an
      increase in p38 activity. Both effects are critical for the induction of
      apoptosis in response to Par-4 expression and UV irradiation. Collectively, these
      results clarify the position of the aPKCs in the UV-induced apoptotic pathway and
      strongly suggest that MAP kinases play a role in this signaling cascade.

PMID- 9234693
TI  - A chimeric enhancer-of-split transcriptional activator drives neural development
      and achaete-scute expression.
AB  - Drosophila melanogaster neurogenesis requires the opposing activities of two sets
      of basic helix-loop-helix (bHLH) proteins: proneural proteins, which confer on
      cells the ability to become neural precursors, and the Enhancer-of-split [E(spl)]
      proteins, which restrict such potential as part of the lateral inhibition
      process. Here, we test if E(spl) proteins function as promoter-bound repressors
      by examining the effects on neurogenesis of an E(spl) derivative containing a
      heterologous transcriptional activation domain [E(spl) m7Act (m7Act)]. In
      contrast to the wild-type E(spl) proteins, m7Act efficiently induces neural
      development, indicating that it binds to and activates target genes normally
      repressed by E(spl). Mutations in the basic domain disrupt m7Act activity,
      suggesting that its effects are mediated through direct DNA binding. m7Act causes
      ectopic transcription of the proneural achaete and scute genes. Our results
      support a model in which E(spl) proteins normally regulate neurogenesis by direct
      repression of genes at the top of the neural determination pathway.

PMID- 9234694
TI  - Nucleosomal structures of c-myc promoters with transcriptionally engaged RNA
      polymerase II.
AB  - Organization of DNA into chromatin has been shown to contribute to a repressed
      state of gene transcription. Disruption of nucleosomal structure is observed in
      response to gene induction, suggesting a model in which RNA polymerase II (pol
      II) is recruited to the promoter upon reorganization of nucleosomes. Here we show
      that induction of c-myc transcription correlates with the disruption of two
      nucleosomes in the upstream promoter region. This nucleosomal disruption,
      however, is not necessary for the binding of pol II to the promoter.
      Transcriptionally engaged pol II complexes can be detected when the upstream
      chromatin is in a more closed configuration. Thus, upstream chromatin opening is
      suggested to affect activation of promoter-bound pol II rather than entry of
      polymerases into the promoter. Interestingly, pol II complexes are detectable in
      both sense and antisense transcriptional directions, but only complexes in the
      sense direction respond to activation signals resulting in processive
      transcription.

PMID- 9234695
TI  - Elements in the 3' untranslated region of procyclin mRNA regulate expression in
      insect forms of Trypanosoma brucei by modulating RNA stability and translation.
AB  - Procyclins are the major surface glycoproteins of insect forms of Trypanosoma
      brucei. We have previously shown that a conserved 16-mer in the 3' untranslated
      region (UTR) of procyclin transcripts functions as a positive element in
      procyclic-form trypanosomes. A systematic analysis of the entire 297-base 3' UTR
      has now revealed additional elements which are involved in posttranscriptional
      regulation: a positive element which requires the first 40 bases of the 3' UTR
      and at least one negative element between nucleotides 101 and 173 (the LII
      domain). Deletion of either positive element resulted in a >8-fold reduction in
      the amount of protein but only an approximately 2-fold decrease in the steady
      state level of mRNA, suggesting that regulation also occurred at the level of
      translation. In contrast, deletion of LII caused a threefold increase in the
      steady-state levels of both the mRNA and protein. LII-16-mer double deletions
      also gave high levels of expression, suggesting that the 16-mer functions as an
      antirepressor of the negative element rather than as an independent activator.
      All three elements have an effect on RNA turnover. When either positive element
      was deleted, the half-life (t(1/2)) of the mRNA was reduced from approximately 50
      min (the t(1/2) of the wild-type 3' UTR) to < 15 min, whereas removal of the LII
      element resulted in an increased t(1/2) of approximately 100 min. We present a
      model of posttranscriptional regulation in which the negative domain is
      counteracted by two positive elements which shield it from nucleases and/or
      translational repressors.

PMID- 9234696
TI  - GABP factors bind to a distal interleukin 2 (IL-2) enhancer and contribute to c
      Raf-mediated increase in IL-2 induction.
AB  - Triggering of the T-cell receptor-CD3 complex activates two major signal cascades
      in T lymphocytes, (i) Ca2+-dependent signal cascades and (ii) protein kinase
      cascades. Both signal cascades contribute to the induction of the interleukin 2
      (IL-2) gene during T-cell activation. Prominent protein kinase cascades are those
      that activate mitogen-activated protein (MAP) kinases. We show here that c-Raf,
      which is at the helm of the classic MAP-Erk cascade, contributes to IL-2
      induction through a distal enhancer element spanning the nucleotides from
      positions -502 to -413 in front of the transcriptional start site of the IL-2
      gene. Induction of this distal IL-2 enhancer differs from induction of the
      proximal IL-2 promoter-enhancer, since it is induced by phorbol esters alone and
      independent from Ca2+ signals. In DNA-protein binding studies, we detected the
      binding of transcription factors GABP alpha and -beta to a dyad symmetry element
      (DSE) of the distal enhancer, which is formed by palindromic binding sites of Ets
      like factors. Introduction of point mutations suppressing GABP binding to the DSE
      interfered with the induction of the distal enhancer and the entire IL-2 promoter
      enhancer, while overexpression of both GABP factors enhanced the IL-2 promoter
      enhancer induction. Overexpression of BXB, a constitutive active version of c
      Raf, and of further members of the Ras-Raf-Erk signal cascade exerted an increase
      of GABP-mediated promoter-enhancer induction. In conjunction with previously
      published data on c-Raf-induced phosphorylation of GABP factors (E. Flory, A.
      Hoffmeyer, U. Smola, U. R. Rapp, and J. T. Bruder, J. Virol. 70:2260-2268, 1996),
      these results indicate a contribution of GABP factors to the Raf-mediated
      enhancement of IL-2 induction during T-cell activation.

PMID- 9234697
TI  - Regulation of IkappaB beta in WEHI 231 mature B cells.
AB  - Constitutive activation of NF-kappaB in WEHI 231 early mature B cells resembles
      the persistent activation of NF-kappaB that is observed upon prolonged
      stimulation of other cells. In both cases, NF-kappaB DNA binding complexes are
      found in the nucleus, despite the abundance of cytosolic IkappaB alpha. Recently,
      we have shown that prolonged activation of 70Z/3 cells with lipopolysaccharide
      results in the degradation of IkappaB beta, followed by its subsequent
      resynthesis as a hypophosphorylated protein. This protein was shown to facilitate
      transport of a portion of NF-kappaB to the nucleus in a manner that protects it
      from cytosolic IkappaB alpha. We now demonstrate that the most abundant form of
      IkappaB beta in WEHI 231 cells is a hypophosphorylated protein. This
      hypophosphorylated IkappaB beta is found in a stable complex with NF-kappaB in
      the cytosol and is also detected in NF-kappaB DNA binding complexes in the
      nucleus. It is likely that hypophosphorylated IkappaB beta in WEHI 231 cells also
      protects NF-kappaB from IkappaB alpha, thus leading to the continuous nuclear
      import of this transcription factor.

PMID- 9234698
TI  - A nucleosome positioned in the distal promoter region activates transcription of
      the human U6 gene.
AB  - To investigate the consequences of chromatin reconstitution for transcription of
      the human U6 gene, we assembled nucleosomes on both plasmids and linear DNA
      fragments containing the U6 gene. Initial experiments with DNA fragments revealed
      that U6 sequences located between the distal sequence element (DSE) and the
      proximal sequence element (PSE) lead to the positioning of a nucleosome partially
      encompassing these promoter elements. Furthermore, indirect end-labelling
      analyses of the reconstituted U6 wild-type plasmids showed strong micrococcal
      nuclease cuts near the DSE and PSE, indicating that a nucleosome is located
      between these elements. To investigate the influence that nucleosomes exert on U6
      transcription, we used two different experimental approaches for chromatin
      reconstitution, both of which resulted in the observation that transcription of
      the U6 wild-type gene was enhanced after chromatin assembly. To ensure that the
      facilitated transcription of the nucleosomal templates is in fact due to a
      positioned nucleosome, we constructed mutants of the U6 gene in which the
      sequences between the DSE and PSE were progressively deleted. In contrast to what
      was observed with the wild-type genes, transcription of these deletion mutants
      was significantly inhibited when they were packaged into nucleosomes.

PMID- 9234699
TI  - Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf
      1/mitogen-activated protein kinase pathway activation.
AB  - Cell attachment to fibronectin stimulates the integrin-dependent interaction of
      p85-associated phosphatidylinositol (PI) 3-kinase with integrin-dependent focal
      adhesion kinase (FAK) as well as activation of the Ras/mitogen-activated protein
      (MAP) kinase pathway. However, it is not known if this PI 3-kinase-FAK
      interaction increases the synthesis of the 3-phosphorylated phosphoinositides (3
      PPIs) or what role, if any, is played by activated PI 3-kinase in integrin
      signaling. We demonstrate here the integrin-dependent accumulation of the PI 3
      kinase products, PI 3,4-bisphosphate [PI(3,4)P2] and PI(3,4,5)P3, as well as
      activation of AKT kinase, a serine/threonine kinase that can be stimulated by
      binding of PI(3,4)P2. The PI 3-kinase inhibitors wortmannin and LY294002
      significantly decreased the integrin-induced accumulation of the 3-PPIs and
      activation of AKT kinase, without having significant effects on the levels of
      PI(4,5)P2 or tyrosine phosphorylation of paxillin. These inhibitors also reduced
      cell adhesion/spreading onto fibronectin but had no effect on attachment to
      polylysine. Interestingly, integrin-mediated Erk-2, Mek-1, and Raf-1 activation,
      but not Ras-GTP loading, was inhibited at least 80% by wortmannin and LY294002.
      In support of the pharmacologic results, fibronectin activation of Erk-2 and AKT
      kinases was completely inhibited by overexpression of a dominant interfering p85
      subunit of PI 3-kinase. We conclude that integrin-mediated adhesion to
      fibronectin results in the accumulation of the PI 3-kinase products PI(3,4)P2 and
      PI(3,4,5)P3 as well as the PI 3-kinase-dependent activation of the kinases Raf-1,
      Mek-1, Erk-2, and AKT and that PI 3-kinase may function upstream of Raf-1 but
      downstream of Ras in integrin activation of Erk-2 MAP and AKT kinases.

PMID- 9234701
TI  - Regulation of T-cell antigen receptor signalling by Syk tyrosine protein kinase.
AB  - T-cell antigen receptor (TCR) signalling has been shown to involve two classes of
      tyrosine protein kinases: the Src-related kinases p56(lck) and p59(fyr), and the
      Zap-70/Syk family kinases. Lck and FynT are postulated to initiate TCR-triggered
      signal transduction by phosphorylating the CD3 and zeta subunits of the TCR
      complex. This modification permits the recruitment of Zap-70 and Syk, which are
      presumed to amplify the TCR-triggered signal, by phosphorylating additional
      intracellular proteins. While Zap-70 is expressed in all T cells, Syk is present
      in thymocytes and mature T-cell populations such as intraepithelial gammadelta T
      cells and naive alphabeta T cells. To better understand the role of Syk in these
      cells, its impact on the physiology of an antigen-specific T-cell line was
      tested. Our results showed that compared to Zap-70 alone, Syk was a strong
      positive regulator of antigen receptor-induced signals in BI-141 cells.
      Surprisingly, they indicated that, like Src family kinases, Syk augmented TCR
      triggered tyrosine phosphorylation of CD3/zeta. Syk, but not Zap-70 alone, could
      also stimulate tyrosine phosphorylation of a zeta-bearing chimera in transiently
      transfected Cos-1 cells. Finally, evidence was provided that Syk has the capacity
      to directly phosphorylate a zeta-derived peptide in vitro. These findings
      suggested that Syk may have a unique role in T cells, as a consequence of its
      ability to efficiently phosphorylate multiple components of the TCR signalling
      cascade. Furthermore, they raised the possibility that Syk can regulate the
      initiation of TCR signalling, by promoting phosphorylation of the immunoreceptor
      tyrosine-based activation motifs of the TCR complex.

PMID- 9234700
TI  - Isolation and characterization of a novel epithelium-specific transcription
      factor, ESE-1, a member of the ets family.
AB  - We report here the isolation of a novel, highly tissue-restricted member of the
      ets transcription factor/oncogene family, ESE-1 (for epithelium-specific Ets),
      which has features distinct from those of any other ets-related factor. ESE-1
      contains two putative DNA binding domains: an ETS domain, which is unique in that
      the 5' half shows relatively weak homology to known ets factors, and an A/T hook
      domain, found in HMG proteins and various other nuclear factors. In contrast to
      any known ets factors, ESE-1 is expressed exclusively in epithelial cells. ESE-1
      expression is induced during terminal differentiation of the epidermis and in a
      primary human keratinocyte differentiation system. The keratinocyte terminal
      differentiation marker gene, SPRR2A, is a putative target for ESE-1, since SPRR2A
      expression during keratinocyte differentiation correlates with induction of ESE-1
      expression, and ESE-1 binds with high affinity to and transactivates the ets
      binding site in the SPRR2A promoter. ESE-1 also binds to and transactivates the
      enhancer of the Endo A gene, a potential target for ESE-1 in simple epithelia.
      Due to the important role that other ets factors play in cellular
      differentiation, ESE-1 is expected to be a critical regulator of epithelial cell
      differentiation.

PMID- 9234702
TI  - Requirement of phosphatidylinositol 3-kinase-dependent pathway and Src for Gas6
      Axl mitogenic and survival activities in NIH 3T3 fibroblasts.
AB  - Gas6 is a secreted protein previously identified as the ligand of the Axl
      receptor tyrosine kinase. We have shown that Gas6 is able to induce cell cycle
      reentry of serum-starved NIH 3T3 cells and to efficiently prevent apoptosis after
      complete growth factor removal, a survival effect uncoupled from Gas6-induced
      mitogenesis. Here we report that the mitogenic effect of Gas6 requires
      phosphatidylinositol 3-kinase (PI3K) activity since it is abrogated both by the
      specific inhibitor wortmannin and by overexpression of the dominant negative P13K
      p85 subunit. Consistently, Gas6 activates the P13K downstream targets S6K and
      Akt, whose activation is abrogated by addition of wortmannin. Moreover, rapamycin
      treatment blocks Gas6-induced entry into the S phase of serum-starved NIH 3T3
      cells. We also demonstrate the requirement of Src tyrosine kinase for Gas6
      signalling since stable or transient expression of a catalytically inactive form
      of Src significantly inhibited Gas6-stimulated entry into the S phase.
      Accordingly, Gas6 addition to serum-starved NIH 3T3 cells causes activation of
      the intrinsic Src kinase activity. When specifically analyzed in a survival
      assay, these elements were found to be required for the survival effect of Gas6.
      Taken together, the evidence presented here identifies elements involved in the
      Gas6 transduction pathway that are responsible for its antiapoptotic effect and
      suggests that Src is involved in the events regulating cell survival.

PMID- 9234703
TI  - Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts.
AB  - Among the mechanisms by which the Ras oncogene induces cellular transformation,
      Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a
      related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is
      additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also
      regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent
      mechanism. A candidate for the physiological effector for both JNK and actin
      regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show
      here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits
      Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90
      to 95% fewer transformed colonies were observed in cotransfection assays with Rat
      1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene,
      indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines
      expressing Pak1(R299) were highly resistant to Ras transformation, while cells
      expressing wild-type Pak1 were efficiently transformed by Ras.
      Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also
      inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by
      Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by
      both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf
      activation of ERK. These results suggest that Pak1 interacts with components
      essential for Ras transformation and that inhibition can be uncoupled from JNK
      but not ERK signaling.

PMID- 9234705
TI  - Evidence that GCN1 and GCN20, translational regulators of GCN4, function on
      elongating ribosomes in activation of eIF2alpha kinase GCN2.
AB  - In the yeast Saccharomyces cerevisiae, phosphorylation of translation initiation
      factor eIF2 by protein kinase GCN2 leads to increased translation of the
      transcriptional activator GCN4 in amino acid-starved cells. The GCN1 and GCN20
      proteins are components of a protein complex required for the stimulation of GCN2
      kinase activity under starvation conditions. GCN20 is a member of the ATP-binding
      cassette (ABC) family, most of the members of which function as membrane-bound
      transporters, raising the possibility that the GCN1/GCN20 complex regulates GCN2
      indirectly as an amino acid transporter. At odds with this idea, indirect
      immunofluorescence revealed cytoplasmic localization of GCN1 and no obvious
      association with plasma or vacuolar membranes. In addition, a fraction of GCN1
      and GCN20 cosedimented with polysomes and 80S ribosomes, and the ribosome
      association of GCN20 was largely dependent on GCN1. The C-terminal 84% of GCN20
      containing the ABCs was found to be dispensable for complex formation with GCN1
      and for the stimulation of GCN2 kinase function. Because ABCs provide the energy
      coupling mechanism for ABC transporters, these results also contradict the idea
      that GCN20 regulates GCN2 as an amino acid transporter. The N-terminal 15 to 25%
      of GCN20, which is critically required for its regulatory function, was found to
      interact with an internal segment of GCN1 similar in sequence to translation
      elongation factor 3 (EF3). Based on these findings, we propose that GCN1 performs
      an EF3-related function in facilitating the activation of GCN2 by uncharged tRNA
      on translating ribosomes. The physical interaction between GCN20 and the EF3-like
      domain in GCN1 could allow for modulation of GCN1 activity, and the ABC domains
      in GCN20 may be involved in this regulatory function. A human homolog of GCN1 has
      been identified, and the portion of this protein most highly conserved with yeast
      GCN1 has sequence similarity to EF3. Thus, similar mechanisms for the detection
      of uncharged tRNA on translating ribosomes may operate in yeast and human cells.

PMID- 9234704
TI  - Functional domains of the Saccharomyces cerevisiae Mlh1p and Pms1p DNA mismatch
      repair proteins and their relevance to human hereditary nonpolyposis colorectal
      cancer-associated mutations.
AB  - The MutL protein is an essential component of the Escherichia coli methyl
      directed mismatch repair system but has no known enzymatic function. In the yeast
      Saccharomyces cerevisiae, the MutL equivalent, an Mlh1p and Pms1p heterodimer,
      interacts with Msh2p bound to mismatch-containing DNA. Little is known of the
      functional domains of Mlh1p and Pms1p. In this report, we define the Mlh1p and
      Pms1p domains required for Mlh1p-Pms1p interaction. The Mlh1p-interactive domain
      of Pms1p is comprised of 260 amino acids near the carboxyl terminus while the
      Pms1p-interactive domain of Mlh1p resides in the final 212 residues. The two
      domains are sufficient for Mlh1p-Pms1p interaction, as determined by the two
      hybrid assay and by in vitro protein affinity chromatography. Deletions within
      the domains completely eliminated Mlh1p-Pms1p interaction. Using site-directed
      mutagenesis, we altered a number of highly conserved residues in the Mlh1p and
      Pms1p proteins, including some alterations that mimic germline mutations observed
      for human hereditary nonpolyposis colorectal cancer. Alterations either in the
      consensus MutL box located in the amino-terminal portion of each protein or in
      the carboxyl-terminal homology motif of Mlh1p eliminated DNA mismatch repair
      function but had no effect on Mlh1p-Pms1p interaction. In addition, certain MLH1
      and PMS1 mutant alleles caused a dominant negative mutator effect when
      overexpressed. We discuss the implications of these findings for the structural
      organization of the Mlh1p and Pms1p proteins and the importance of Mlh1p-Pms1p
      interaction.

PMID- 9234706
TI  - Identification of RTF1, a novel gene important for TATA site selection by TATA
      box-binding protein in Saccharomyces cerevisiae.
AB  - Interaction of the TATA box-binding protein (TBP) with promoters of RNA
      polymerase II-transcribed genes is an early and essential step in mRNA synthesis.
      Previous studies have demonstrated that the rate-limiting binding of TBP to a
      TATA element can be influenced by transcriptional regulatory proteins. To
      identify additional factors that may regulate DNA binding by TBP in vivo, we
      performed a genetic selection for extragenic suppressors of a yeast TBP mutant
      that exhibits altered and relaxed DNA binding specificity. This analysis has led
      to the discovery of a previously unidentified gene, RTF1. The original rtf1
      suppressor mutation, which encodes a single amino acid change in Rtf1, and an
      rtf1 null allele suppress the effects of the TBP specificity mutant by altering
      transcription initiation. Differences in the patterns of transcription initiation
      in these strains strongly suggest that the rtf1 missense mutation is distinct
      from a simple loss-of-function allele. The results of genetic crosses indicate
      that suppression of TBP mutants by mutations in RTF1 occurs in an allele-specific
      fashion. In a strain containing wild-type TBP, the rtf1 null mutation suppresses
      the transcriptional effects of a Ty delta insertion mutation in the promoter of
      the HIS4 gene, a phenotype also conferred by the TBP altered-specificity mutant.
      Finally, as shown by indirect immunofluorescence experiments, Rtf1 is a nuclear
      protein. Taken together, our findings suggest that Rtf1 either directly or
      indirectly regulates the DNA binding properties of TBP and, consequently, the
      relative activities of different TATA elements in vivo.

PMID- 9234707
TI  - Expression of wild-type alpha-catenin protein in cells with a mutant alpha
      catenin gene restores both growth regulation and tumor suppressor activities.
AB  - Recent studies indicate that disruption of the E-cadherin-mediated cell-cell
      adhesion system is frequently associated with human cancers of epithelial origin.
      Reduced levels of both E-cadherin and the associated protein, alpha-catenin, have
      been reported in human tumors. This report describes the characterization of a
      human ovarian carcinoma-derived cell line (Ov2008) which expresses a novel mutant
      form of the alpha-catenin protein lacking the extreme N terminus of the wild-type
      protein. The altered form of alpha-catenin expressed in Ov2008 cells fails to
      bind efficiently to beta-catenin and is localized in the cytoplasm. Deletion
      mapping has localized the beta-catenin binding site on alpha-catenin between
      amino acids 46 and 149, which encompasses the same region of the protein that is
      deleted in the Ov2008 variant. Restoration of inducible expression of the wild
      type alpha-catenin protein in these cells caused them to assume the morphology
      typical of an epithelial sheet and retarded their growth in vitro. Additionally,
      the induction of alpha-catenin expression in Ov2008 cells injected into nude mice
      attenuated the ability of these cells to form tumors. These observations support
      the classification of alpha-catenin as a growth-regulatory and candidate tumor
      suppressor gene.

PMID- 9234709
TI  - Type I elements mediate replication fork pausing at conserved upstream sites in
      the Tetrahymena thermophila ribosomal DNA minichromosome.
AB  - Two-dimensional gel electrophoresis was used to study replication of the
      Tetrahymena thermophila ribosomal DNA (rDNA) minichromosome. During vegetative
      growth, the rDNA is replicated exclusively from origins in the 5' nontranscribed
      spacer (NTS). Whereas replication fork movement through the rest of the
      chromosome appears to be continuous, movement through the 5' NTS is not.
      Replication forks arrest transiently at three prominent replication fork pausing
      sites (RFPs) located in or immediately adjacent to nucleosome-free regions of the
      5' NTS. Pausing at these sites is dramatically diminished during replication in
      Escherichia coli, suggesting that chromatin organization or Tetrahymena-specific
      proteins may be required. A conserved tripartite sequence was identified at each
      pausing site. Mutations in type I elements diminish pausing at proximal RFPs.
      Hence, type I elements, previously shown to control replication initiation, also
      regulate elongation of existing replication forks. Studies with rDNA
      transformants revealed a strong directional bias for fork pausing. Strong pausing
      only occurred in forks moving toward the rRNA-coding region. We propose that fork
      pausing in the 5' NTS evolved to synchronize replication and transcription of the
      downstream rRNA genes.

PMID- 9234708
TI  - Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory event
      for Ras-dependent activation and biological signaling.
AB  - Activation of the Raf serine/threonine protein kinases is tightly regulated by
      multiple phosphorylation events. Phosphorylation of either tyrosine 340 or 341 in
      the catalytic domain of Raf-1 has been previously shown to induce the ability of
      the protein kinase to phosphorylate MEK. By using a combination of mitogenic and
      enzymatic assays, we found that phosphorylation of the adjacent residue, serine
      338, and, to a lesser extent, serine 339 is essential for the biological and
      enzymatic activities of Raf-1. Replacement of S338 with alanine blocked the
      ability of prenylated Raf-CX to transform Rat-1 fibroblasts. Similarly, the loss
      of S338-S339 in Raf-1 prevented protein kinase activation in COS-7 cells by
      either oncogenic Ras[V12] or v-Src. Consistent with phosphorylation of S338-S339,
      acidic amino acid substitutions of these residues partially restored transforming
      activity to Raf-CX, as well as kinase activation of Raf-1 by Ras[V12] or v-Src.
      Two-dimensional phosphopeptide mapping of wild-type Raf-CX and Raf-CX[A338A339]
      confirmed the presence of a phosphoserine-containing peptide with the predicted
      mobility in the wild-type protein which was absent from the mutant. This peptide
      could be quantitatively precipitated by an antipeptide antibody specific for the
      18-residue tryptic peptide containing S338-S339 and was demonstrated to contain
      only phosphoserine. Phosphorylation of this peptide in Raf-1 was significantly
      increased by coexpression with Ras[V12]. These data demonstrate that Raf-1
      residues 338 to 341 constitute a unique phosphoregulatory site in which the
      phosphorylation of serine and tyrosine residues contributes to the regulation of
      Raf by Ras, Src, and Ras-independent membrane localization.

PMID- 9234710
TI  - The Mauriceville retroplasmid reverse transcriptase initiates cDNA synthesis de
      novo at the 3' end of tRNAs.
AB  - The Mauriceville retroplasmid of Neurospora mitochondria encodes a novel reverse
      transcriptase that initiates cDNA synthesis de novo (i.e., without a primer) at
      the 3' CCA of the plasmid transcript's 3' tRNA-like structure (H. Wang and A. M.
      Lambowitz, Cell 75:1071-1081, 1993). Here, we show that the plasmid reverse
      transcriptase also initiates cDNA synthesis de novo at the 3' end of tRNAs,
      leading to synthesis of a full-length cDNA copy of the tRNA. The use of tRNA
      templates in vivo was suggested previously by the structure of suppressive mutant
      plasmids that have incorporated mitochondrial tRNA sequences (R. A. Akins, R. L.
      Kelley, and A. M. Lambowitz, Cell 47:505-516, 1986). The in vitro experiments
      show that efficient de novo initiation on tRNA templates requires an unpaired 3'
      CCA and occurs predominantly opposite position C-2 of the 3' CCA sequence, the
      same position as in the plasmid transcript. In other reactions, the plasmid
      reverse transcriptase synthesizes cDNA dimers by template switching between two
      tRNA templates and initiates at an internal position in a tRNA by using the 3'
      end of the tRNA as a primer. Finally, we show that template switching between the
      tRNA and the plasmid transcript in vitro gives rise to hybrid cDNAs of the type
      predicted to be intermediates in the generation of the suppressive mutant
      plasmids. The ability of the plasmid reverse transcriptase to initiate at the 3'
      end of tRNAs presumably reflects the recognition of structural features similar
      to those of the 3' tRNA-like structure of the plasmid transcript. The recognition
      of tRNAs or tRNA-like structures as templates for cDNA synthesis may be
      characteristic of primitive reverse transcriptases that evolved from RNA
      dependent RNA polymerases.

PMID- 9234711
TI  - Domains required for dimerization of yeast Rad6 ubiquitin-conjugating enzyme and
      Rad18 DNA binding protein.
AB  - The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme
      required for postreplicational repair of UV-damaged DNA and for damage-induced
      mutagenesis. In addition, Rad6 functions in the N end rule pathway of protein
      degradation. Rad6 mediates its DNA repair role via its association with Rad18,
      whose DNA binding activity may target the Rad6-Rad18 complex to damaged sites in
      DNA. In its role in N end-dependent protein degradation, Rad6 interacts with the
      UBR1-encoded ubiquitin protein ligase (E3) enzyme. Previous studies have
      indicated the involvement of N-terminal and C-terminal regions of Rad6 in
      interactions with Ubr1. Here, we identify the regions of Rad6 and Rad18 that are
      involved in the dimerization of these two proteins. We show that a region of 40
      amino acids towards the C terminus of Rad18 (residues 371 to 410) is sufficient
      for interaction with Rad6. This region of Rad18 contains a number of nonpolar
      residues that have been conserved in helix-loop-helix motifs of other proteins.
      Our studies indicate the requirement for residues 141 to 149 at the C terminus,
      and suggest the involvement of residues 10 to 22 at the N terminus of Rad6, in
      the interaction with Rad18. Each of these regions of Rad6 is indicated to form an
      amphipathic helix.

PMID- 9234712
TI  - A basic motif in the N-terminal region of RAG1 enhances V(D)J recombination
      activity.
AB  - The variable portions of antigen receptor genes are assembled from component gene
      segments by a site-specific recombination reaction known as V(D)J recombination.
      The RAG1 and RAG2 proteins are the critical lymphoid cell-specific components of
      the recombination enzymatic machinery and are responsible for site-specific DNA
      recognition and cleavage. Previous studies had defined a minimal,
      recombinationally active core region of murine RAG1 consisting of amino acids 384
      to 1008 of the 1,040-residue RAG1 protein. No recombination function has
      heretofore been ascribed to any portion of the 383-amino-acid N-terminal region
      that is missing from the core, but it seems likely to be of functional
      significance, based on its evolutionary conservation. Using extrachromosomal
      recombination substrates, we demonstrate here that the N-terminal region enhances
      the recombination activity of RAG1 by up to an order of magnitude in a variety of
      cell lines. Deletion analysis localized a region of the N terminus critical for
      this effect to amino acids 216 to 238, and further mutagenesis demonstrated that
      a small basic amino acid motif (BIIa) in this region is essential for enhancing
      the activity of RAG1. Despite the fact that BIIa is important for the interaction
      of RAG1 with the nuclear localization factor Srp-1, it does not appear to enhance
      recombination by facilitating nuclear transport of RAG1. A variety of models for
      how this region stimulates the recombination activity of RAG1 are considered.

PMID- 9234713
TI  - Enhancer control of local accessibility to V(D)J recombinase.
AB  - We have studied the role of transcriptional enhancers in providing recombination
      signal sequence (RSS) accessibility to V(D)J recombinase by examining mice
      carrying a transgenic human T-cell receptor (TCR) delta gene minilocus. This
      transgene is composed of unrearranged variable (Vdelta and Vdelta2), diversity
      (Ddelta3), joining (Jdelta1 and Jdelta3), and constant (Cdelta) gene segments.
      Previous data indicated that with the TCR delta enhancer (Edelta) present in the
      Jdelta3-Cdelta intron, V(D)J recombination proceeds stepwise, first V to D and
      then VD to J. With the enhancer deleted or mutated, V-to-D rearrangement is
      intact, but VD-to-J rearrangement is inhibited. We proposed that Edelta is
      necessary for J segment but not D segment accessibility and that J segment
      inaccessibility in the enhancerless minilocus resulted in the observed V(D)J
      recombination phenotype. In this study, we tested this notion by using ligation
      mediated PCR to assess the formation of recombination-activating gene (RAG)
      dependent double-strand breaks (DSBs) at RSSs 3' of Ddelta3 and 5' of Jdelta1. In
      five lines of mice carrying multicopy integrants of constructs that either lacked
      Edelta or carried an inactivated Edelta, the frequency of DSBs 5' of Jdelta1 was
      dramatically reduced relative to that in the wild type, whereas the frequency of
      DSBs 3' of Ddelta3 was unaffected. We interpret these results to indicate that
      Edelta is required for Jdelta1 but not Ddelta3 accessibility within the
      minilocus, and we conclude that enhancers regulate V(D)J recombination by
      providing local accessibility to the recombinase. cis-acting elements other than
      Edelta must maintain Ddelta3 in an accessible state in the absence of Edelta. The
      analysis of DSB formation in a single-copy minilocus integrant indicates that
      efficient DSB formation at the accessible RSS 3' of Ddelta3 requires an
      accessible partner RSS, arguing that RSS synapsis is required for DSB formation
      in chromosomal substrates in vivo.

PMID- 9234714
TI  - G triplets located throughout a class of small vertebrate introns enforce intron
      borders and regulate splice site selection.
AB  - Splicing of small introns in lower eucaryotes can be distinguished from
      vertebrate splicing by the inability of such introns to be expanded and by the
      inability of splice site mutations to cause exon skipping-properties suggesting
      that the intron rather than the exon is the unit of recognition. Vertebrates do
      contain small introns. To see if they possess properties similar to small introns
      in lower eucaryotes, we studied the small second intron from the human alpha
      globin gene. Mutation of the 5' splice site of this intron resulted in in vivo
      intron inclusion, not exon skipping, suggesting the presence of intron bridging
      interactions. The intron had an unusual base composition reflective of a sequence
      bias present in a collection of small human introns in which multiple G triplets
      stud the interior of the introns. Each G triplet represented a minimal sequence
      element additively contributing to maximal splicing efficiency and spliceosome
      assembly. More importantly, G triplets proximal to a duplicated splice site
      caused preferential utilization of the 5' splice site upstream of the triplets or
      the 3' splice site downstream of the triplets; i.e., sequences containing G
      triplets were preferentially used as introns when a choice was possible. Thus, G
      triplets internal to a small intron have the ability to affect splice site
      decisions at both ends of the intron. Each G triplet additively contributed to
      splice site selectivity. We suggest that G triplets are a common component of
      human 5' splice sites and aid in the definition of exon-intron borders as well as
      overall splicing efficiency. In addition, our data suggest that such intronic
      elements may be characteristic of small introns and represent an intronic
      equivalent to the exon enhancers that facilitate recognition of both ends of an
      exon during exon definition.

PMID- 9234716
TI  - CCAAT-binding factor NF-Y and RFX are required for in vivo assembly of a
      nucleoprotein complex that spans 250 base pairs: the invariant chain promoter as
      a model.
AB  - The events that lead to promoter accessibility within chromatin are not
      completely understood. The invariant chain (Ii) promoter was used as a model to
      determine the contribution of different DNA-binding factors in establishing
      occupancy of a complex promoter. Gamma interferon induction of the Ii promoter
      requires the cooperation of multiple cis elements including distal S, X, and
      Y/CCAAT elements along with proximal GC and Y/CCAAT elements. The heteromeric
      transcription factor NF-Y binds to both Y/CCAAT elements. Genomic footprinting
      was used to analyze in vivo protein-DNA contacts for integrated Ii promoters
      bearing mutations in each element. The results reveal a hierarchy of
      transcription factor loading with NF-Y binding to the distal Y/CCAAT element
      being required for establishing protein-DNA interactions over the entire 250 bp
      analyzed. Mutation of the X box disrupts binding primarily at the adjacent
      Y/CCAAT element along with a lesser effect on GC box binding. Importantly, this
      finding is verified with a cell line which lacks a functional X-box-binding
      factor, RFX, providing physiological validity for the strategy described here.
      Mutation of both the S element and the GC box results in either no or little
      effect on transcription factor binding. However, mutation of the proximal Y/CCAAT
      element disrupts binding to the adjacent GC box and partially reduces binding in
      the distal S/X/Y domain. The crucial role for NF-Y in establishing promoter
      occupancy may be related to its histone fold motif, the essential component for
      assembling nucleosome-like structures.

PMID- 9234715
TI  - Multiple control elements mediate activation of the murine and human interleukin
      12 p40 promoters: evidence of functional synergy between C/EBP and Rel proteins.
AB  - Interleukin 12 (IL-12) is a heterodimeric cytokine whose activity is critical for
      T-helper 1 responses. The gene for the IL-12 p40 subunit is expressed in
      macrophages following induction by bacterial products, and its expression is
      augmented by gamma interferon. In this study, we performed a functional analysis
      of the murine and human p40 promoters in the murine macrophage cell line RAW
      264.7. Transcription from the murine p40 promoter was strongly induced by
      lipopolysaccharide and heat-killed Listeria monocytogenes (HKLM), but promoter
      activity was not enhanced by gamma interferon. Multiple cis-acting elements
      involved in activated transcription were identified through an extensive mutant
      analysis. The most critical element, whose activity is conserved in mice and
      humans, is located between positions -96 and -88 relative to the murine
      transcription start site. This element exhibits functional synergy with a
      previously described NF-kappaB half-site which interacts with Rel proteins. DNase
      I footprinting and electrophoretic mobility shift assays demonstrated that C/EBP
      proteins interact with the critical element, but in nuclear extracts, cooperative
      binding of C/EBP and Rel proteins to their respective sites was not observed.
      Interestingly, promoter activity was induced by HKLM in the presence of
      cycloheximide, consistent with induction by posttranslational mechanisms. The
      results suggest that C/EBP and Rel proteins play important roles in the
      activation of IL-12 p40 transcription by bacteria. However, many complex
      interactions will need to be clarified to fully understand p40 regulation.

PMID- 9234717
TI  - Phosphotyrosine binding domain-dependent upregulation of the platelet-derived
      growth factor receptor alpha signaling cascade by transforming mutants of Cbl:
      implications for Cbl's function and oncogenicity.
AB  - Recent studies have demonstrated that Cbl, the 120-kDa protein product of the c
      cbl proto-oncogene, serves as a substrate of a number of receptor-coupled
      tyrosine kinases and forms complexes with SH3 and SH2 domain-containing proteins,
      pointing to its role in signal transduction. Based on genetic evidence that the
      Caenorhabditis elegans Cbl homolog, SLI-1, functions as a negative regulator of
      the LET-23 receptor tyrosine kinase and our demonstration that Cbl's
      evolutionarily conserved N-terminal transforming region (Cbl-N; residues 1 to
      357) harbors a phosphotyrosine binding (PTB) domain that binds to activated ZAP
      70 tyrosine kinase, we examined the possibility that oncogenic Cbl mutants may
      activate mitogenic signaling by deregulating cellular tyrosine kinase machinery.
      Here, we show that expression of Cbl-N and two other transforming Cbl mutants
      (CblY368 delta and Cbl366-382 delta or Cb170Z), but not wild-type Cbl, in NIH 3T3
      fibroblasts leads to enhancement of endogenous tyrosine kinase signaling. We
      identified platelet-derived growth factor receptor alpha (PDGFR alpha) as one
      target of mutant Cbl-induced deregulation. In mutant Cbl transfectants, PDGFR
      alpha was hyperphosphorylated and constitutively complexed with a number of SH2
      domain-containing proteins. PDGFR alpha hyperphosphorylation and enhanced
      proliferation of mutant Cbl-transfected NIH 3T3 cells were drastically reduced
      upon serum starvation, and PDGF-AA substituted for the maintenance of these
      traits. PDGF-AA stimulation of serum-starved Cbl transfectants induced the in
      vivo association of transfected Cbl proteins with PDGFR alpha. In vitro, Cbl-N
      directly bound to PDGFR alpha derived from PDGF-AA-stimulated cells but not to
      that from unstimulated cells, and this binding was abrogated by a point mutation
      (G306E) corresponding to a loss-of-function mutation in SLI-1. The Cbl-N/G306E
      mutant protein, which failed to induce enhanced growth and transformation of NIH
      3T3 cells, also failed to induce hyperphosphorylation of PDGFR alpha. Altogether,
      these findings identify a novel mechanism of Cbl's physiological function and
      oncogenesis, involving its PTB domain-dependent direct interaction with cellular
      tyrosine kinases.

PMID- 9234718
TI  - Modulation of the fate of cytoplasmic mRNA by AU-rich elements: key sequence
      features controlling mRNA deadenylation and decay.
AB  - Regulation of cytoplasmic deadenylation has a direct impact on the fate of mRNA
      and, consequently, its expression in the cytoplasm. AU-rich elements (AREs) found
      in the 3' untranslated regions of many labile mRNAs are the most common RNA
      destabilizing elements known in mammalian cells. AREs direct accelerated
      deadenylation as the first step in mRNA turnover. Recently we have proposed that
      AREs can be divided into three different classes. mRNAs bearing either the class
      I AUUUA-containing ARE or the class III non-AUUUA ARE display synchronous poly(A)
      shortening, whereas class II ARE-containing mRNAs are deadenylated
      asynchronously, with the formation of poly(A)- intermediates. In this study, we
      have systematically characterized the deadenylation kinetics displayed by various
      AREs and their mutant derivatives. We find that a cluster of five or six copies
      of AUUUA motifs in close proximity forming various degrees of reiteration is the
      key feature that dictates the choice between processive versus distributive
      deadenylation. An AU-rich region 20 to 30 nucleotides long immediately 5' to this
      cluster of AUUUA motifs can greatly enhance the destabilizing ability of the
      AUUUA cluster and is, therefore, an integral part of the class I and class II
      AREs. These two features are the defining characteristics of class II AREs. Our
      results are consistent with the interpretation that the pentanucleotide AUUUA,
      rather than the nonamer UUAUUUA(U/A)(U/A), is both an essential and the minimal
      sequence motif of AREs. Our study provides the groundwork for future
      characterization of ARE-binding proteins identified by in vitro gel shift assays
      in order to stringently define their potential role in the ARE-mediated decay
      pathway. Moreover, transformation of deadenylation kinetics from one type to the
      other by mutations of AREs implies the existence of cross talk between the ARE
      and 3' poly(A) tail, which dictates the decay kinetics.

PMID- 9234719
TI  - A transcriptional mediator protein that is required for activation of many RNA
      polymerase II promoters and is conserved from yeast to humans.
AB  - A temperature-sensitive mutation was obtained in Med6p, a component of the
      mediator complex from the yeast Saccharomyces cerevisiae. The mediator complex
      has been shown to enable transcriptional activation in vitro. This mutation in
      Med6p abolished activation of transcription from four of five inducible promoters
      tested in vivo. There was no effect, however, on uninduced transcription,
      transcription of constitutively expressed genes, or transcription by RNA
      polymerases I and III. Mediator-RNA polymerase II complex isolated from the
      mutant yeast strain was temperature sensitive for transcriptional activation in a
      reconstituted in vitro system due to a defect in initiation complex formation. A
      database search revealed the existence of MED6-related genes in humans and
      Caenorhabditis elegans, suggesting that the role of mediator in transcriptional
      activation is conserved throughout the evolution.

PMID- 9234721
TI  - Probing the structure and function of the estrogen receptor ligand binding domain
      by analysis of mutants with altered transactivation characteristics.
AB  - We have developed a genetic screen for the yeast Saccharomyces cerevisiae to
      isolate estrogen receptor (ER) mutants with altered transactivation
      characteristics. Use of a "reverse" ER, in which the mutagenized ligand binding
      domain was placed at the N terminus of the receptor, eliminated the isolation of
      truncated constitutively active mutants. A library was screened with a low
      affinity estrogen, 2-methoxyestrone (2ME), at concentrations 50-fold lower than
      those required for activation of the unmutagenized ER. Several mutants displaying
      enhanced sensitivity to 2ME were isolated. We further characterized a mutant
      carrying the substitution L536P, which was located immediately N terminal to the
      AF-2-activating domain of the receptor. Amino acid 536 corresponds to a ligand
      contact residue in retinoic acid receptor gamma, suggesting that key contact
      points are conserved among receptors. Introduction of L536P into the original ER
      cDNA isolate HE0, which contains the substitution G400V, rendered the receptor
      more sensitive to a variety of agonists. When introduced into the wild-type ER
      HEG0, L536P also rendered the receptor more sensitive to agonists, and, in
      addition, induced high levels of constitutive activity that could be inhibited by
      antiestrogens. Estrogens containing a keto substitution in the steroid D ring,
      but not those containing a hydroxyl group, were full agonists of L536P-HEG0.
      Limited proteolytic analysis suggested that the L536P substitution, which is
      located immediately N terminal to the AF-2 domain, induces a conformational
      change in the ER that partially mimics binding by hormone. Both HEG0 and L536P
      HEG0 formed complexes with hsp90 in vitro, indicating a lack of correlation
      between interaction with hsp90 in vitro and hormonal regulation of ER
      transactivation in vivo. This supports the idea that a factor(s) acting
      downstream of hsp90 is important for controlling activity of the hormone-free
      receptor.

PMID- 9234720
TI  - Differentiation of central nervous system neuronal cells by fibroblast-derived
      growth factor requires at least two signaling pathways: roles for Ras and Src.
AB  - To evaluate the role of mitogen-activated protein (MAP) kinase and other
      signaling pathways in neuronal cell differentiation by basic fibroblast-derived
      growth factor (bFGF), we used a conditionally immortalized cell line from rat
      hippocampal neurons (H19-7). Previous studies have shown that activation of MAP
      kinase kinase (MEK) is insufficient to induce neuronal differentiation of H19-7
      cells. To test the requirement for MEK and MAP kinase (ERK1 and ERK2), H19-7
      cells were treated with the MEK inhibitor PD098059. Although the MEK inhibitor
      blocked the induction of differentiation by constitutively activated Raf, the H19
      7 cells still underwent differentiation by bFGF. These results suggest that an
      alternative pathway is utilized by bFGF for differentiation of the hippocampal
      neuronal cells. Expression in the H19-7 cells of a dominant-negative Ras (N17
      Ras) or Raf (C4-Raf) blocked differentiation by bFGF, suggesting that Ras and
      probably Raf are required. Expression of dominant-negative Src (pcSrc295Arg) or
      microinjection of an anti-Src antibody blocked differentiation by bFGF in H19-7
      cells, indicating that bFGF also signals through a Src kinase-mediated pathway.
      Although neither constitutively activated MEK (MEK-2E) nor v-Src was sufficient
      individually to differentiate the H19-7 cells, coexpression of constitutively
      activated MEK and v-Src induced neurite outgrowth. These results suggest that (i)
      activation of MAP kinase (ERK1 and ERK2) is neither necessary nor sufficient for
      differentiation by bFGF; (ii) activation of Src kinases is necessary but not
      sufficient for differentiation by bFGF; and (iii) differentiation of H19-7
      neuronal cells by bFGF requires at least two signaling pathways activated by Ras
      and Src.

PMID- 9234722
TI  - Structure-function analysis of the Saccharomyces cerevisiae G1 cyclin Cln2.
AB  - We have generated 50 new alleles of the yeast CLN2 gene by using site-directed
      mutagenesis. With the recently obtained crystal structure of cyclin A as a guide,
      a peptide linker sequence was inserted at 13 sites within the cyclin box of Cln2
      to determine if the architecture of Cln2 is similar to that of cyclin A. Linkers
      inserted in what are predicted to be helices 1, 2, 3, and 5 of the cyclin box
      resulted in nonfunctional Cln2 molecules. Linkers inserted between these putative
      helix sites and in the region believed to contain a fourth helix did not have
      significant effects upon Cln2 function. A series of deletions in the region
      between the third and fifth helices indicate that the putative fourth helix may
      lie at the C-terminal end of this region yet is not essential for function. Two
      residues that are predicted to form a buried salt bridge important for
      interaction of two helices of the cyclin box were also mutated, and an additional
      set of 31 mutant alleles was generated by clustered-charge-to-alanine scanning
      mutagenesis. All of the mutant CLN2 alleles made in this study were tested in a
      variety of genetic and functional assays previously demonstrated to differentiate
      specific cyclin functions. Some alleles demonstrated restricted patterns of
      defects, suggesting that these mutations may interfere with specific aspects of
      Cln2 function.

PMID- 9234723
TI  - The polypyrimidine tract binding protein binds upstream of neural cell-specific c
      src exon N1 to repress the splicing of the intron downstream.
AB  - The neural cell-specific N1 exon of the c-src pre-mRNA is both negatively
      regulated in nonneural cells and positively regulated in neurons. We previously
      identified conserved intronic elements flanking N1 that direct the repression of
      N1 splicing in a nonneural HeLa cell extract. The upstream repressor elements are
      located within the polypyrimidine tract of the N1 exon 3' splice site. A short
      RNA containing this 3' splice site sequence can sequester trans-acting factors in
      the HeLa extract to allow splicing of N1. We now show that these upstream
      repressor elements specifically interact with the polypyrimidine tract binding
      protein (PTB). Mutations in the polypyrimidine tract reduce both PTB binding and
      the ability of the competitor RNA to derepress splicing. Moreover, purified PTB
      protein restores the repression of N1 splicing in an extract derepressed by a
      competitor RNA. In this system, the PTB protein is acting across the N1 exon to
      regulate the splicing of N1 to the downstream exon 4. This mechanism is in
      contrast to other cases of splicing regulation by PTB, in which the protein
      represses the splice site to which it binds.

PMID- 9234724
TI  - Mutational analysis of acute-phase response factor/Stat3 activation and
      dimerization.
AB  - Signal transducer and transcription (STAT) factors are activated by tyrosine
      phosphorylation in response to a variety of cytokines, growth factors, and
      hormones. Tyrosine phosphorylation triggers dimerization and nuclear
      translocation of these transcription factors. In this study, the functional role
      of carboxy-terminal portions of the STAT family member acute-phase response
      factor/Stat3 in activation, dimerization, and transactivating potential was
      analyzed. We demonstrate that truncation of 55 carboxy-terminal amino acids
      causes constitutive activation of Stat3 in COS-7 cells, as is known for the Stat3
      isoform Stat3beta. By the use of deletion and point mutants, it is shown that
      both carboxy- and amino-terminal portions of Stat3 are involved in this
      phenomenon. Dimerization of Stat3 was blocked by point mutations affecting
      residues both in the vicinity of the tyrosine phosphorylation site (Y705) and
      more distant from this site, suggesting that multiple interactions are involved
      in dimer formation. Furthermore, by reporter gene assays we demonstrate that
      carboxy-terminally truncated Stat3 proteins are incapable of transactivating an
      interleukin-6-responsive promoter in COS-7 cells. In HepG2 hepatoma cells,
      however, these truncated Stat3 forms transmit signals from the interleukin-6
      signal transducer gp130 equally well as does full-length Stat3. We conclude that,
      dependent on the cell type, different mechanisms allow Stat3 to regulate target
      gene transcription either with or without involvement of its putative carboxy
      terminal transactivation domain.

PMID- 9234725
TI  - Mutations in the conserved C-terminal sequence in thyroid hormone receptor
      dissociate hormone-dependent activation from interference with AP-1 activity.
AB  - A short C-terminal sequence that is deleted in the v-ErbA oncoprotein and
      conserved in members of the nuclear receptor superfamily is required for normal
      biological function of its normal cellular counterpart, the thyroid hormone
      receptor alpha (T3R alpha). We carried out an extensive mutational analysis of
      this region based on the crystal structure of the hormone-bound ligand binding
      domain of T3R alpha. Mutagenesis of Leu398 or Glu401, which are surface exposed
      according to the crystal structure, completely blocks or significantly impairs T3
      dependent transcriptional activation but does not affect or only partially
      diminishes interference with AP-1 activity. These are the first mutations that
      clearly dissociate these activities for T3R alpha. Substitution of Leu400, which
      is also surface exposed, does not affect interference with AP-1 activity and only
      partially diminishes T3-dependent transactivation. None of the mutations affect
      ligand-independent transactivation, consistent with previous findings that this
      activity is mediated by the N-terminal domain of T3R alpha. The loss of ligand
      dependent transactivation for some mutants can largely be reversed in the
      presence of GRIP1, which acts as a strong ligand-dependent coactivator for wild
      type T3R alpha. There is excellent correlation between T3-dependent in vitro
      association of GRIP1 with T3R alpha mutants and their ability to support T3
      dependent transcriptional activation. Therefore, GRIP1, previously found to
      interact with the glucocorticoid, estrogen, and androgen receptors, may also have
      a role in T3R alpha-mediated ligand-dependent transcriptional activation. When
      fused to a heterologous DNA binding domain, that of the yeast transactivator
      GAL4, the conserved C terminus of T3R alpha functions as a strong ligand
      independent activator in both mammalian and yeast cells. However, point mutations
      within this region have drastically different effects on these activities
      compared to their effect on the full-length T3R alpha. We conclude that the C
      terminal conserved region contains a recognition surface for GRIP1 or a similar
      coactivator that facilitates its interaction with the basal transcriptional
      apparatus. While important for ligand-dependent transactivation, this interaction
      surface is not directly involved in transrepression of AP-1 activity.

PMID- 9234726
TI  - Pbx raises the DNA binding specificity but not the selectivity of antennapedia
      Hox proteins.
AB  - We have used a binding site selection strategy to determine the optimal binding
      sites for Pbx proteins by themselves and as heterodimeric partners with various
      Hox gene products. Among the Pbx proteins by themselves, only Pbx3 binds with
      high affinity, as a monomer or as a homodimer, to an optimal binding site,
      TGATTGATTTGAT. An inhibitory domain located N terminal of the Pbx1 homeodomain
      prevents intrinsic Pbx1 binding to this sequence. When complexed with Hoxc-6,
      each of the Pbx gene products binds the same consensus sequence, TGATTTAT, which
      differs from the site bound by Pbx3 alone. Three members of the Antennapedia
      family, Hoxc-6, Hoxb-7, and Hoxb-8, select the same binding site in conjunction
      with Pbx1. The affinities of these proteins as heterodimeric partners with Pbx1
      for the selected optimal binding site are similar. However, the binding
      specificity of Hox proteins for optimal binding sites is increased, compared to
      nonspecific DNA, in the presence of Pbx proteins. Thus, while cooperative DNA
      binding involving heterodimers of Pbx and Hox gene products derived from members
      within the Antennapedia family does not increase binding site selectivity, DNA
      binding specificity of the Hox gene products is significantly enhanced in the
      presence of Pbx.

PMID- 9234727
TI  - The product of the murine homolog of the Drosophila extra sex combs gene displays
      transcriptional repressor activity.
AB  - The heterogeneous nuclear ribonucleoprotein K protein represents a novel class of
      proteins that may act as docking platforms that orchestrate cross-talk among
      molecules involved in signal transduction and gene expression. Using a fragment
      of K protein as bait in the yeast two-hybrid screen, we isolated a cDNA that
      encodes a protein whose primary structure has extensive similarity to the
      Drosophila melanogaster extra sex combs (esc) gene product, Esc, a putative
      silencer of homeotic genes. The cDNA that we isolated is identical to the cDNA of
      the recently positionally cloned mouse embryonic ectoderm development gene, eed.
      Like Esc, Eed contains six WD-40 repeats in the C-terminal half of the protein
      and is thought to repress homeotic gene expression during mouse embryogenesis.
      Eed binds to K protein through a domain in its N terminus, but interestingly,
      this domain is not found in the Drosophila Esc. Gal4-Eed fusion protein represses
      transcription of a reporter gene driven by a promoter that contains Gal4-binding
      DNA elements. Eed also represses transcription when recruited to a target
      promoter by Gal4-K protein. Point mutations within the eed gene that are
      responsible for severe embryonic development abnormalities abolished the
      transcriptional repressor activity of Eed. Results of this study suggest that Eed
      restricted homeotic gene expression during embryogenesis reflects the action of
      Eed as a transcriptional repressor. The Eed-mediated transcriptional effects are
      likely to reflect the interaction of Eed with multiple molecular partners,
      including K protein.

PMID- 9234728
TI  - Genetic redundancy between SPT23 and MGA2: regulators of Ty-induced mutations and
      Ty1 transcription in Saccharomyces cerevisiae.
AB  - SPT23 was isolated as a dosage-dependent suppressor of Ty-induced mutations in
      Saccharomyces cerevisiae. SPT23 shows considerable sequence homology with MGA2, a
      gene identified as a dosage-dependent suppressor of a snf2-imposed block on STA1
      transcription in S. cerevisiae var. diastaticus. Although single mutations in
      either of these genes have only modest effects on cell growth, spt23 mga2 double
      mutants are inviable. Unlike SPT23, multicopy expression of a truncated form of
      MGA2 suppresses a narrow subset of Ty-induced mutations. SPT23/MGA2 and the
      SNF/SWI genes affect transcription of certain target genes in similar ways.
      Spt23p appears to be a rate-limiting component required for functional HIS4
      expression of his4-912delta, a promoter insertion mutation induced by the Ty1-912
      long terminal repeat. Furthermore, both Spt23p and Mga2p can activate
      transcription when fused to the Gal4p DNA-binding domain, as previously observed
      with Snf2p and Snf5p. A 50-amino-acid region in the N terminus of the predicted
      Spt23p protein is necessary and sufficient for the transactivation and necessary
      for suppression of Ty1-induced mutations and the essential function of Spt23p.
      Cell fractionation and cytological experiments suggest that Spt23p is associated
      with the nucleus. Our results suggest that SPT23/MGA2 affects transcription of a
      subset of genes in yeast, perhaps by changing chromatin accessibility.

PMID- 9234729
TI  - Evidence for a role for galectin-1 in pre-mRNA splicing.
AB  - Galectins are a family of beta-galactoside-binding proteins that contain
      characteristic amino acid sequences in the carbohydrate recognition domain (CRD)
      of the polypeptide. The polypeptide of galectin-1 contains a single domain, the
      CRD. The polypeptide of galectin-3 has two domains, a carboxyl-terminal CRD fused
      onto a proline- and glycine-rich amino-terminal domain. In previous studies, we
      showed that galectin-3 is a required factor in the splicing of nuclear pre-mRNA,
      assayed in a cell-free system. We now document that (i) nuclear extracts derived
      from HeLa cells contain both galectins-1 and -3; (ii) depletion of both galectins
      from the nuclear extract either by lactose affinity adsorption or by double
      antibody adsorption results in a concomitant loss of splicing activity; (iii)
      depletion of either galectin-1 or galectin-3 by specific antibody adsorption
      fails to remove all of the splicing activity, and the residual splicing activity
      is still saccharide inhibitable; (iv) either galectin-1 or galectin-3 alone is
      sufficient to reconstitute, at least partially, the splicing activity of nuclear
      extracts depleted of both galectins; and (v) although the carbohydrate
      recognition domain of galectin-3 (or galectin-1) is sufficient to restore
      splicing activity to a galectin-depleted nuclear extract, the concentration
      required for reconstitution is greater than that of the full-length galectin-3
      polypeptide. Consistent with these functional results, double-immunofluorescence
      analyses show that within the nucleus, galectin-3 colocalizes with the speckled
      structures observed with splicing factor SC35. Similar results are also obtained
      with galectin-1, although in this case, there are areas of galectin-1 devoid of
      SC35 and vice versa. Thus, nuclear galectins exhibit functional redundancy in
      their splicing activity and partition, at least partially, in the nucleoplasm
      with another known splicing factor.

PMID- 9234730
TI  - Both thyroid hormone and 9-cis retinoic acid receptors are required to
      efficiently mediate the effects of thyroid hormone on embryonic development and
      specific gene regulation in Xenopus laevis.
AB  - Tissue culture transfection and in vitro biochemical studies have suggested that
      heterodimers of thyroid hormone receptors (TRs) and 9-cis retinoic acid receptors
      (RXRs) are the likely in vivo complexes that mediate the biological effects of
      thyroid hormone, 3,5,3'-triiodothyronine (T3). However, direct in vivo evidence
      for such a hypothesis has been lacking. We have previously reported a close
      correlation between the coordinated expression of TR and RXR genes and tissue
      dependent temporal regulation of organ transformations during Xenopus laevis
      metamorphosis. By introducing TRs and RXRs either individually or together into
      developing Xenopus embryos, we demonstrate here that RXRs are critical for the
      developmental function of TRs. Precocious expression of TRs and RXRs together but
      not individually leads to drastic, distinct embryonic abnormalities, depending
      upon the presence or absence of T3, and these developmental effects require the
      same receptor domains as those required for transcriptional regulation by TR-RXR
      heterodimers. More importantly, the overexpressed TR-RXR heterodimers faithfully
      regulate endogenous T3 response genes that are normally regulated by T3 only
      during metamorphosis. That is, they repress the genes in the absence of T3 and
      activate them in the presence of the hormone. On the other hand, the receptors
      have no effect on a retinoic acid (RA) response gene. Thus, RA- and T3 receptor
      mediated teratogenic effects in Xenopus embryos occur through distinct molecular
      pathways, even though the resulting phenotypes have similarities.

PMID- 9234731
TI  - Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD.
AB  - The muscle LIM protein (MLP) is a muscle-specific LIM-only factor that exhibits a
      dual subcellular localization, being present in both the nucleus and in the
      cytoplasm. Overexpression of MLP in C2C12 myoblasts enhances skeletal myogenesis,
      whereas inhibition of MLP activity blocks terminal differentiation. Thus, MLP
      functions as a positive developmental regulator, although the mechanism through
      which MLP promotes terminal differentiation events remains unknown. While
      examining the distinct roles associated with the nuclear and cytoplasmic forms of
      MLP, we found that nuclear MLP functions through a physical interaction with the
      muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and
      myogenin. This interaction is highly specific since MLP does not associate with
      nonmuscle bHLH proteins E12 or E47 or with the myocyte enhancer factor-2 (MEF2)
      protein, which acts cooperatively with the myogenic bHLH proteins to promote
      myogenesis. The first LIM motif in MLP and the highly conserved bHLH region of
      MyoD are responsible for mediating the association between these muscle-specific
      factors. MLP also interacts with MyoD-E47 heterodimers, leading to an increase in
      the DNA-binding activity associated with this active bHLH complex. Although MLP
      lacks a functional transcription activation domain, we propose that it serves as
      a cofactor for the myogenic bHLH proteins by increasing their interaction with
      specific DNA regulatory elements. Thus, the functional complex of MLP-MyoD-E
      protein reveals a novel mechanism for both initiating and maintaining the
      myogenic program and suggests a global strategy for how LIM-only proteins may
      control a variety of developmental pathways.

PMID- 9234732
TI  - The amino-terminal transforming region of simian virus 40 large T and small t
      antigens functions as a J domain.
AB  - Simian virus 40 (SV40) encodes two proteins, large T antigen and small t antigen
      that contribute to virus-induced tumorigenesis. Both proteins act by targeting
      key cellular regulatory proteins and altering their function. Known targets of
      the 708-amino-acid large T antigen include the three members of the
      retinoblastoma protein family (pRb, p107, and p130), members of the CBP family of
      transcriptional adapter proteins (cap-binding protein [CBP], p300, and p400), and
      the tumor suppressor p53. Small t antigen alters the activity of phosphatase pp2A
      and transactivates the cyclin A promoter. The first 82 amino acids of large T
      antigen and small t antigen are identical, and genetic experiments suggest that
      an additional target(s) important for transformation interacts with these
      sequences. This region contains a motif similar to the J domain, a conserved
      sequence found in the DnaJ family of molecular chaperones. We show here that
      mutations within the J domain abrogate the ability of large T antigen to
      transform mammalian cells. To examine whether a purified 136-amino-acid fragment
      from the T antigen amino terminus acts as a DnaJ-like chaperone, we investigated
      whether this fragment stimulates the ATPase activity of two hsc70s and discovered
      that ATP hydrolysis is stimulated four- to ninefold. In addition, ATPase
      defective mutants of full-length T antigen, as well as wild-type small t antigen,
      stimulated the ATPase activity of hsc70. T antigen derivatives were also able to
      release an unfolded polypeptide substrate from an hsc70, an activity common to
      DnaJ chaperones. Because the J domain of T antigen plays essential roles in viral
      DNA replication, transcriptional control, virion assembly, and tumorigenesis, we
      conclude that this region may chaperone the rearrangement of multiprotein
      complexes.

PMID- 9234733
TI  - Illegitimate recombination leading to allelic loss and unbalanced translocation
      in p53-mutated human lymphoblastoid cells.
AB  - Allelic loss and translocation are critical mutational events in human
      tumorigenesis. Allelic loss, which is usually identified as loss of
      heterozygosity (LOH), is frequently observed at tumor suppressor loci in various
      kinds of human tumors. It is generally thought to result from deletion or mitotic
      recombination between homologous chromosomes. In this report, we demonstrate that
      illegitimate (nonhomologous) recombination strongly contributes to the generation
      of allelic loss in p53-mutated cells. Spontaneous and X-ray-induced LOH mutations
      at the heterozygous thymidine kinase (tk) gene, which is located on the long arm
      of chromosome 17, from normal (TK6) and p53-mutated (WTK-1) human lymphoblastoid
      cells were cytogenetically analyzed by chromosome 17 painting. We observed
      unbalanced translocations in 53% of LOH mutants spontaneously arising from WTK-1
      cells but none spontaneously arising from TK6 cells. We postulate that
      illegitimate recombination was occurring between nonhomologous chromosomes after
      DNA replication, leading to allelic loss and unbalanced translocations in p53
      mutated WTK-1 cells. X-ray irradiation, which induces DNA double-strand breaks
      (DSBs), enhanced the generation of unbalanced translocation more efficiently in
      WTK-1 than in TK6 cells. This observation implicates the wild-type p53 protein in
      the regulation of homologous recombination and recombinational DNA repair of DSBs
      and suggests a possible mechanism by which loss of p53 function may cause genomic
      instability.

PMID- 9234734
TI  - E2A deficiency leads to abnormalities in alphabeta T-cell development and to
      rapid development of T-cell lymphomas.
AB  - The E2A gene products, E12 and E47, are critical for proper early B-cell
      development and commitment to the B-cell lineage. Here we reveal a new role for
      E2A in T-lymphocyte development. Loss of E2A activity results in a partial block
      at the earliest stage of T-lineage development. This early T-cell phenotype
      precedes the development of a T-cell lymphoma which occurs between 3 and 9 months
      of age. The thymomas are monoclonal and highly malignant and display a cell
      surface phenotype similar to that of immature thymocytes. In addition, the
      thymomas generally express high levels of c-myc. As assayed by comparative
      genomic hybridization, each of the tumor populations analyzed showed a nonrandom
      gain of chromosome 15, which contains the c-myc gene. Taken together, the data
      suggest that the E2A gene products play a role early in thymocyte development
      that is similar to their function in B-lineage determination. Furthermore, the
      lack of E2A results in development of T-cell malignancies, and we propose that
      E2A inactivation is a common feature of a wide variety of human T-cell
      proliferative disorders, including those involving the E2A heterodimeric partners
      tal-1 and lyl-1.

PMID- 9234736
TI  - Identification of drm, a novel gene whose expression is suppressed in transformed
      cells and which can inhibit growth of normal but not transformed cells in
      culture.
AB  - Using differential display analysis, we compared the expression of RNA in v-mos
      transformed cells and their flat revertant and isolated a novel gene, drm (down
      regulated in mos-transformed cells), whose expression is down-regulated in
      parental v-mos-transformed cells but which is expressed at a high level in the
      revertant and normal rat fibroblasts (REF-1 cells). Analysis of different
      oncogene-transformed cells revealed that drm gene expression was also suppressed
      in REF-1 cells transformed by v-ras, v-src, v-raf, and v-fos. The drm cDNA
      contains a 184-amino-acid-protein-encoding open reading frame which shows no
      significant homologies to known genes in DNA databases. Polyclonal antibodies
      raised against drm peptide detect a protein with the predicted size of 20.7 kDa
      in normal cells and under nonpermissive conditions in cells conditionally
      transformed by v-mos but not in parental v-mos-transformed cells. Northern
      analysis of normal adult tissues shows that drm is expressed as a 4.4-kb message
      in a tissue-specific manner, with high expression in the brain, spleen, kidney,
      and testis and little or no expression in the heart, liver, and skeletal muscle.
      In situ hybridization analysis in adult rat tissue reveals good correlation with
      this pattern and indicates that drm mRNA is most highly expressed in nondividing
      and terminally differentiated cells, such as neurons, type 1 lung cells, and
      goblet cells. Transfection of a drug-selectable drm expression vector
      dramatically reduced the efficiency of colony formation in REF-1 and CHO cells,
      and the drm-transfected REF-1 survivors expressed low or nondetectable levels of
      exogenous drm mRNA. The toxic effects of drm can be overcome by cotransfection
      with constructs expressing oncogenic ras; furthermore, cells expressing high
      levels of drm and conditionally transformed with mos-expressing Moloney murine
      sarcoma virus rapidly undergo apoptosis when shifted to the nonpermissive
      temperature. Taken together, our data suggest that cells expressing high levels
      of drm undergo apoptotic death in the absence of oncogene-induced transformation
      and that drm represents a novel gene with potential roles in cell growth control
      or viability and tissue-specific differentiation.

PMID- 9234737
TI  - The yeast SWI-SNF complex facilitates binding of a transcriptional activator to
      nucleosomal sites in vivo.
AB  - The Saccharomyces cerevisiae SWI-SNF complex is a 2-MDa protein assembly that is
      required for the function of many transcriptional activators. Here we describe
      experiments on the role of the SWI-SNF complex in activation of transcription by
      the yeast activator GAL4. We find that while SWI-SNF activity is not required for
      the GAL4 activator to bind to and activate transcription from nucleosome-free
      binding sites, the complex is required for GAL4 to bind to and function at low
      affinity, nucleosomal binding sites in vivo. This SWI-SNF dependence can be
      overcome by (i) replacing the low-affinity sites with higher-affinity, consensus
      GAL4 binding sequences or (ii) placing the low-affinity sites into a nucleosome
      free region. These results define the criteria for the SWI-SNF dependence of gene
      expression and provide the first in vivo evidence that the SWI-SNF complex can
      regulate gene expression by modulating the DNA binding of an upstream activator
      protein.

PMID- 9234735
TI  - The level of intracellular glutathione is a key regulator for the induction of
      stress-activated signal transduction pathways including Jun N-terminal protein
      kinases and p38 kinase by alkylating agents.
AB  - Monofunctional alkylating agents like methyl methanesulfonate (MMS) and N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) are potent inducers of cellular stress leading
      to chromosomal aberrations, point mutations, and cell killing. We show that these
      agents induce a specific cellular stress response program which includes the
      activation of Jun N-terminal kinases/stress-activated protein kinases
      (JNK/SAPKs), p38 mitogen-activated protein kinase, and the upstream kinase
      SEK1/MKK4 and which depends on the reaction mechanism of the alkylating agent in
      question. Similar to another inducer of cellular stress, UV irradiation, damage
      of nuclear DNA by alkylation is not involved in the MMS-induced response.
      However, in contrast to UV and other inducers of the JNK/SAPKs and p38 pathways,
      activation of growth factor and G-protein-coupled receptors does not play a role
      in the MMS response. We identified the intracellular glutathione (GSH) level as
      critical for JNK/SAPK activation by MMS: enhancing the GSH level by pretreatment
      of the cells with GSH or N-acetylcysteine inhibits, whereas depletion of the
      cellular GSH pool causes hyperinduction of JNK/SAPK activity by MMS. In light of
      the JNK/SAPK-dependent induction of c-jun and c-fos transcription, and the
      Jun/Fos-induced transcription of xenobiotic-metabolizing enzymes, these data
      provide a potential critical role of JNK/SAPK and p38 in the induction of a
      cellular defense program against cytotoxic xenobiotics such as MMS.

PMID- 9234738
TI  - Two evolutionarily conserved repression domains in the Drosophila Kruppel protein
      differ in activator specificity.
AB  - To identify biologically functional regions in the product of the Drosophila
      melanogaster gene Kruppel, we cloned the Kruppel homolog from Drosophila virilis.
      Both the previously identified amino (N)-terminal repression region and the DNA
      binding region of the D. virilis Kruppel protein are greater than 96% identical
      to those of the D. melanogaster Kruppel protein, demonstrating a selective
      pressure to maintain the integrity of each region during 60 million to 80 million
      years of evolution. An additional region in the carboxyl (C) terminus of Kruppel
      that was most highly conserved was examined further. A 42-amino-acid stretch
      within the conserved C-terminal region also encoded a transferable repression
      domain. The short, C-terminal repression region is a composite of three
      subregions of distinct amino acid composition, each containing a high proportion
      of either basic, proline, or acidic residues. Mutagenesis experiments
      demonstrated, unexpectedly, that the acidic residues contribute to repression
      function. Both the N-terminal and C-terminal repression regions were tested for
      the ability to affect transcription mediated by a variety of activator proteins.
      The N-terminal repression region was able to inhibit transcription in the
      presence of multiple activators. However, the C-terminal repression region
      inhibited transcription by only a subset of the activator proteins. The different
      activator specificities of the two regions suggest that they repress
      transcription by different mechanisms and may play distinct biological roles
      during Drosophila development.

PMID- 9234739
TI  - Characterization of the Wtm proteins, a novel family of Saccharomyces cerevisiae
      transcriptional modulators with roles in meiotic regulation and silencing.
AB  - Transcription is regulated by the complex interplay of repressors and activators.
      Much of this regulation is carried out by, in addition to gene-specific factors,
      complexes of more general transcriptional modulators. Here we present the
      characterization of a novel family of transcriptional regulators in yeast. Wtm1p
      (WD repeat-containing transcriptional modulator) was identified as a protein
      present in a large nuclear complex. This protein has two homologs, Wtm2p and
      Wtm3p, which probably arose by gene duplications. Deletion of these genes affects
      transcriptional repression at several loci, including derepression of IME2, a
      meiotic gene normally repressed in haploid cells. Targeting of these proteins to
      DNA resulted in a dramatic repression of activated transcription. In common with
      a mutation in the histone deacetylase RPD3, wtm mutants showed increased
      repression at the silent mating-type locus, HMR, and at telomeres. Although all
      three Wtm proteins could act as transcriptional repressors, Wtm3p, which is the
      least homologous, appeared to have functions separate from those of the other
      two. Wtm3p did not appear to be complexed with the other two proteins, was
      essential for IME2 repression, and could not efficiently repress transcription in
      the absence of the other Wtm proteins. These data suggested that Wtm1p and Wtm2p
      are repressors and that Wtm3p has different effects on transcription at different
      loci.

PMID- 9234740
TI  - Molecular analysis of the SNF2/SWI2 protein family member MOT1, an ATP-driven
      enzyme that dissociates TATA-binding protein from DNA.
AB  - MOT1 is an essential Saccharomyces cerevisiae protein and a member of the
      SNF2/SWI2 family of ATPases. MOT1 functions by removing TATA-binding protein
      (TBP) from DNA, and as a consequence, MOT1 can regulate transcription both in
      vitro and in vivo. Here we describe the in vivo and in vitro activities of MOT1
      deletion and substitution mutants. The results indicate that MOT1 is targeted to
      TBP both in vitro and in vivo via amino acids in its nonconserved N terminus. The
      conserved C-terminal ATPase of MOT1 appears to contribute to TBP-DNA complex
      recognition in the absence of ATP, but it appears to function primarily during
      the actual ATP-dependent dissociation reaction. Chimeric proteins in which
      homologous portions of SNF2/SWI2 have been substituted for the MOT1 ATPase can
      bind to TBP-DNA complexes but fail to dissociate these complexes in the presence
      of ATP, suggesting that the specificity of action of MOT1 is also conferred by
      the C-terminal ATPase. ATPase assays demonstrate that the MOT1 ATPase is
      activated by TBP. Thus, MOT1 undergoes at least two conformational changes: (i)
      an allosteric effect of TBP that mediates the activation of the MOT1 ATPase and
      (ii) an ATP-driven "power stroke" that causes TBP-DNA complex dissociation. These
      results provide a general framework for understanding how members of the
      SNF2/SWI2 protein family use ATP to modulate protein-DNA interactions to regulate
      many diverse processes in cells.

PMID- 9234741
TI  - A large protein complex containing the yeast Sin3p and Rpd3p transcriptional
      regulators.
AB  - The SIN3 gene is required for the transcriptional repression of diverse genes in
      Saccharomyces cerevisiae. Sin3p does not bind directly to DNA but is thought to
      be targeted to promoters by interacting with sequence-specific DNA-binding
      proteins. We show here that Sin3p is present in a large multiprotein complex with
      an apparent molecular mass, estimated by gel filtration chromatography, of
      greater than 2 million Da. Genetic studies have shown that the yeast RPD3 gene
      has a function similar to that of SIN3 in transcriptional regulation, as SIN3 and
      RPD3 negatively regulate the same set of genes. The SIN3 and RPD3 genes are
      conserved from yeasts to mammals, and recent work suggests that RPD3 may encode a
      histone deacetylase. We show that Rpd3p is present in the Sin3p complex and that
      an rpd3 mutation eliminates SIN3-dependent repression. Thus, Sin3p may function
      as a bridge to recruit the Rpd3p histone deacetylase to specific promoters.

PMID- 9234742
TI  - Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor
      alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling.
AB  - Fusion proteins involving the retinoic acid receptor alpha (RAR alpha) and the
      PML or PLZF nuclear protein are the genetic markers of acute promyelocytic
      leukemias (APLs). APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion
      protein are phenotypically indistinguishable except that they differ in their
      sensitivity to retinoic acid (RA)-induced differentiation: PML-RAR alpha blasts
      are sensitive to RA and patients enter disease remission after RA treatment,
      while patients with PLZF-RAR alpha do not. We here report that (i) like PML-RAR
      alpha expression, PLZF-RAR alpha expression blocks terminal differentiation of
      hematopoietic precursor cell lines (U937 and HL-60) in response to different
      stimuli (vitamin D3, transforming growth factor beta1, and dimethyl sulfoxide);
      (ii) PML-RAR alpha, but not PLZF-RAR alpha, increases RA sensitivity of
      hematopoietic precursor cells and restores RA sensitivity of RA-resistant
      hematopoietic cells; (iii) PML-RAR alpha and PLZF-RAR alpha have similar RA
      binding affinities; and (iv) PML-RAR alpha enhances the RA response of RA target
      genes (those for RAR beta, RAR gamma, and transglutaminase type II [TGase]) in
      vivo, while PLZF-RAR alpha expression has either no effect (RAR beta) or an
      inhibitory activity (RAR gamma and type II TGase). These data demonstrate that
      PML-RAR alpha and PLZF-RAR alpha have similar (inhibitory) effects on RA
      independent differentiation and opposite (stimulatory or inhibitory) effects on
      RA-dependent differentiation and that they behave in vivo as RA-dependent
      enhancers or inhibitors of RA-responsive genes, respectively. Their different
      activities on the RA signalling pathway might underlie the different responses of
      PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment. The PLZF-RAR alpha fusion
      protein contains an approximately 120-amino-acid N-terminal motif (called the POZ
      domain), which is also found in a variety of zinc finger proteins and a group of
      poxvirus proteins and which mediates protein-protein interactions. Deletion of
      the PLZF POZ domain partially abrogated the inhibitory effect of PLZF-RAR alpha
      on RA-induced differentiation and on RA-mediated type II TGase up-regulation,
      suggesting that POZ-mediated protein interactions might be responsible for the
      inhibitory transcriptional activities of PLZF-RAR alpha.

PMID- 9234743
TI  - Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component
      of the alpha-globin mRNA stability complex.
AB  - mRNA turnover is an important regulatory component of gene expression and is
      significantly influenced by ribonucleoprotein (RNP) complexes which form on the
      mRNA. Studies of human alpha-globin mRNA stability have identified a specific RNP
      complex (alpha-complex) which forms on the 3' untranslated region (3'UTR) of the
      mRNA and appears to regulate the erythrocyte-specific accumulation of alpha
      globin mRNA. One of the protein activities in this multiprotein complex is a
      poly(C)-binding activity which consists of two proteins, alphaCP1 and alphaCP2.
      Neither of these proteins, individually or as a pair, can bind the alpha-globin
      3'UTR unless they are complexed with the remaining non-poly(C) binding proteins
      of the alpha-complex. With the yeast two-hybrid screen, a second alpha-complex
      protein was identified. This protein is a member of the previously identified A+U
      rich (ARE) binding/degradation factor (AUF1) family of proteins, which are also
      known as the heterogeneous nuclear RNP (hnRNP) D proteins. We refer to these
      proteins as AUF1/hnRNP-D. Thus, a protein implicated in ARE-mediated mRNA decay
      is also an integral component of the mRNA stabilizing alpha-complex. The
      interaction of AUF1/hnRNP-D is more efficient with alphaCP1 relative to alphaCP2
      both in vitro and in vivo, suggesting that the alpha-complex might be dynamic
      rather than a fixed complex. AUF1/hnRNP-D could, therefore, be a general mRNA
      turnover factor involved in both stabilization and decay of mRNA.

PMID- 9234744
TI  - WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent
      kinases.
AB  - The p21(WAF1/CIP1/sdi1) gene product (WAF1) inhibits DNA replication in vitro (J.
      Chen, P. Jackson, M. Kirschner, and A. Dutta, Nature 374:386-388, 1995; S. Waga,
      G. Hannon, D. Beach, and B. Stillman, Nature 369:574-578, 1994), but in vivo
      studies on the antiproliferative activity of WAF1 have not resolved G1-phase
      arrest from potential inhibition of S-phase progression. Here, we demonstrate
      that elevated WAF1 expression can retard replicative DNA synthesis in vivo. The
      WAF1-mediated inhibitory effect could be antagonized by cyclin A, cyclin E, or
      the simian virus 40 small-t antigen with no decrease in the levels of WAF1
      protein in transfected cells. Proliferating-cell nuclear antigen (PCNA)
      overexpression was neither necessary nor sufficient to antagonize WAF1 action.
      Expression of the N-terminal domain of WAF1, responsible for cyclin-dependent
      kinase (CDK) interaction, had the same effect as full-length WAF1, while the PCNA
      binding C terminus exhibited modest activity. We conclude that S-phase
      progression in mammalian cells is dependent on continuing cyclin and CDK activity
      and that WAF1 affects S phase primarily through cyclin- and CDK-dependent
      pathways.

PMID- 9234745
TI  - Role of pili in Haemophilus influenzae adherence and colonization.

PMID- 9234746
TI  - Plasmodium falciparum AARP1, a giant protein containing repeated motifs rich in
      asparagine and aspartate residues, is associated with the infected erythrocyte
      membrane.
AB  - During Plasmodium falciparum asexual intraerythrocytic development, the host's
      cell plasma membrane is modified by the insertion of parasite proteins. One or
      more of these modifications mediate the cytoadherence of infected erythrocytes to
      host vascular endothelium. However, these surface antigens can be the target of
      cytophilic antibodies which promote phagocytosis of the infected erythrocyte. It
      has been proposed that antibodies directed to epitopes rich in asparagine play an
      important role in this process, which has promoted efforts to isolate the
      corresponding gene(s). We describe here P. falciparum asparagine- and aspartate
      rich protein 1 (PfAARP1), a new giant (circa 700-kDa) protein associated with the
      infected erythrocyte membrane which is rich in asparagine and aspartate residues
      due to the presence of nine blocks of repeats. Topology analysis predicts that
      PfAARP1 has multiple transmembrane domains and at least five external loops.
      Human antibodies immunopurified against a sequence composed exclusively of
      asparagine and aspartate amino acids derived from PfAARP1 label the surface of
      the infected erythrocyte, demonstrating that such motifs are exposed.
      Interestingly, external loop 4 of PfAARP1 contains repetitions of these residues,
      and their possible role as a target of cytophilic antibodies is discussed.

PMID- 9234747
TI  - Diphosphoryl lipid A from Rhodobacter sphaeroides inhibits complexes that form in
      vitro between lipopolysaccharide (LPS)-binding protein, soluble CD14, and
      spectrally pure LPS.
AB  - An early event in septic shock is the activation of macrophages by a complex
      consisting of lipopolysaccharide (LPS), LPS-binding protein (LBP), and the cell
      surface antigen CD14. The complexes that form between [3H]ReLPS (ReLPS is deep
      rough-chemotype hexacyl LPS from E. coli D31m4), soluble CD14 (sCD14), and LBP
      were analyzed by two independent methods, native (nondenaturing) gel
      electrophoresis and size-exclusion high-performance liquid chromatography (HPLC).
      This is the first reported use of HPLC to purify and study LPS-protein complexes.
      The binding of [3H]ReLPS to LBP and sCD14 was inhibited by preincubation with
      diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA), a potent LPS
      antagonist. In addition, [3H]ReLPS bound to LBP and to a truncated form of sCD14
      [sCD14(1-152)] that contained the LPS binding domain. Binding to both proteins
      was blocked by RsDPLA. Thus, RsDPLA competes in a 1:1 ratio for the same or
      nearby binding sites on ReLPS complexes. Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of aggregated ReLPS eluting from the HPLC
      indicated that only LBP, not sCD14, was bound to the aggregated ReLPS. This
      finding supports the binary model of LPS complex formation with LBP and sCD14.

PMID- 9234748
TI  - Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune
      human sera is associated with antibodies to the gamete surface antigen Pfs230.
AB  - Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230
      and Pfs48/45, can abolish the infectivity of gametes to mosquitoes; these
      antigens have been proposed as candidates for inclusion in a malaria transmission
      blocking vaccine. One possible mechanism of antibody-mediated transmission
      blocking is complement-mediated gamete lysis. We have used a panel of human sera
      from geographically distinct regions where malaria is endemic to investigate
      whether this may be a mechanism of naturally acquired transmission-blocking
      immunity to P. falciparum. By immunoprecipitation, we have shown that antibody
      recognition of Pfs230 and Pfs48/45 is limited, despite universal exposure to P.
      falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum
      gametes was positively associated with the presence of antibodies to Pfs230 but
      not with antibodies to the N-terminal region of the precursor molecule (Pfs260),
      which is shed from the gametocyte surface at the time of gametogenesis.
      Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and
      Pfg27/25, were not associated with gamete lysis. All sera which mediate gamete
      lysis contain immunoglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface
      proteins as determined by an enzyme-linked immunosorbent assay. These data
      suggest that Pfs230 is a major target of complement-fixing antibodies which may
      be important for antibody-mediated transmission-blocking immunity.

PMID- 9234749
TI  - Characterization of human T- and B-cell epitopes in the C terminus of Plasmodium
      falciparum merozoite surface protein 1: evidence for poor T-cell recognition of
      polypeptides with numerous disulfide bonds.
AB  - We have investigated the relationship between cellular and humoral immune
      responses to defined epitopes of the C terminus of merozoite surface protein 1
      (MSP-1) of the human malaria parasite, Plasmodium falciparum, in immune blood
      donors. Sera from almost all donors contained antibodies to the 33-kDa processing
      product of the MAD20 allele of MSP-1 (MSP-1(33)), but these antibodies did not
      cross-react with the equivalent sequence of the Wellcome allele. In contrast, T
      cell responses to MSP-1(33) are directed towards epitopes that are conserved
      between the two allelic families. Only 50% of adult blood donors possessed
      antibodies which recognized the 19-kDa processing product of MSP-1 (MSP-1(19)).
      These antibodies predominantly recognized conserved epitopes involving both of
      the constituent epidermal growth factor-like domains of MSP-1(19). T-cell
      responses were found in only 26% (for recombinant proteins) or 44% (for synthetic
      peptides) of donors and were directed mainly at dimorphic sequences of the
      protein. There was no obvious association, at an individual level, between the
      presence of antibodies and the detection of T-cell proliferative or gamma
      interferon responses, suggesting that the T cells identified in this manner are
      not providing significant levels of help to B cells. T-cell responses to reduced
      recombinant proteins and linear peptides were more prevalent than responses to
      disulfide-bonded proteins, suggesting that the complex disulfide-bonded structure
      of native MSP-1(19) may inhibit antigen processing or presentation.

PMID- 9234750
TI  - Comparison of protection induced by immunization with recombinant proteins from
      different regions of merozoite surface protein 1 of Plasmodium yoelii.
AB  - Vaccination with native full-length merozoite surface protein 1 (MSP1) or with
      recombinant C-terminal peptides protects mice against lethal challenge with
      virulent malaria parasites. To determine whether other regions of MSP1 can also
      induce protection, Plasmodium yoelii MSP1 was divided into four separate regions.
      Each was expressed in Escherichia coli as a fusion protein with glutathione S
      transferase (GST). The N-terminal fragment began after the cleavage site for the
      signal sequence and ended in the region comparable to the cleavage site for the C
      terminus of the 82-kDa peptide of Plasmodium falciparum. This expressed protein
      was 30 kDa smaller than the predicted peptide. One peptide from the middle region
      was produced, and the C terminus consisted of a 42-kDa fragment corresponding to
      the analogous peptide of P. falciparum and a 19-kDa fragment that extended 37
      amino acids in the amino-terminal direction beyond the probable cleavage site. To
      test protection of mice against lethal P. yoelii challenge, three mouse strains
      (CAF1, BALB/c, and A/J) were vaccinated with each of the four recombinant
      proteins of MSP1. Mice vaccinated with the C-terminal 19-kDa protein were highly
      protected (described previously), as were those vaccinated with the 42-kDa
      protein that contained the 19-kDa fragment. The N-terminally expressed fragment
      of P. yoelii was not full length because of proteolytic cleavage in E. coli. The
      GST-82-kDa partial fragments induced some immunity, but the surviving mice still
      had high parasitemias. Vaccination with the peptide from the middle region of
      MSP1 gave minimal to no protection. Therefore, in addition to the C-terminal 19-
      and 42-kDa proteins, the only other fragment to give protection was the 82-kDa
      protein. The protection induced by the truncated 82-kDa protein was minimal
      compared with that of the C-terminal fragments.

PMID- 9234752
TI  - Dipeptidyl-peptidase IV secreted by Aspergillus fumigatus, a fungus pathogenic to
      humans.
AB  - A dipeptidyl-peptidase IV was purified from the culture medium of the human
      pathogenic fungus Aspergillus fumigatus. The enzyme has an apparent molecular
      mass of 95 kDa and contained approximately 10 kDa of N-linked carbohydrate. This
      glycoprotein is antigenic and has all characteristics of the class IV dipeptidyl
      peptidases: removal of Xaa-Pro and to a lesser extent Xaa-Ala dipeptides from the
      N termini of peptides, including bioactive peptides such as neuropeptide Y, [des
      Arg1] bradykinin, and glucagon-like peptide 1, activity at neutral pH, and
      presence in the amino acid sequence of the Gly-X-Ser-X-Gly consensus motif of the
      serine-hydrolases and the putative catalytic triad (Ser613, Asp690, His725) of
      the dipeptidyl-peptidases. Moreover, the last 200 amino acids displayed 60 to 65%
      similarity with the other dipeptidyl-peptidases IV from rat, mouse, human, and
      yeast. However, unlike the other dipeptidyl-peptidases, the dipeptidyl-peptidase
      IV of A. fumigatus is a secreted enzyme with a cleavable signal peptide.
      Expression of a recombinant dipeptidyl-peptidase IV of A. fumigatus has been
      attained in the yeast Pichia pastoris.

PMID- 9234753
TI  - Attenuation and vaccine potential of aroQ mutants of Corynebacterium
      pseudotuberculosis.
AB  - Corynebacterium pseudotuberculosis, a gram-positive intracellular bacterial
      pathogen, is the etiological agent of the disease caseous lymphadenitis (CLA) in
      both sheep and goats. Attenuated mutants of C. pseudotuberculosis have the
      potential to act as novel live veterinary vaccine vectors. We have cloned and
      sequenced the aroB and aroQ genes from C. pseudotuberculosis C231. By allelic
      exchange, aroQ mutants of both C231, designated CS100, and a pld mutant strain
      TB521, designated CS200, were constructed. Infection of BALB/c mice indicated
      that introduction of the aroQ mutation into C231 and TB521 attenuated both
      strains. In sublethally infected BALB/c mice, both CS100 and CS200 were cleared
      from spleens and livers by day 8 postinfection. The in vivo persistence of these
      strains was increased when the intact aroQ gene was supplied on a plasmid in
      trans. Mice infected with TB521 harbored bacteria in organs at least till day 8
      postinfection without ill effect. When used as a vaccine, only the maximum
      tolerated dose of CS100 had the capacity to protect mice from homologous
      challenge. Vaccination with TB521 also elicited protective immunity, and this was
      associated with gamma interferon (IFN-gamma) production from splenocytes
      stimulated 7 days postvaccination. The role of IFN-gamma in controlling primary
      infections with C. pseudotuberculosis was examined in mice deficient for the IFN
      gamma receptor (IFN-gammaR(-/-) mice). IFN-gammaR(-/-) mice cleared an infection
      with CS100 but were significantly more susceptible than control littermates to
      infection with C231 or TB521. These studies support an important role for IFN
      gamma in control of primary C. pseudotuberculosis infections and indicate that
      aroQ mutants remain attenuated even in immunocompromised animals. This is the
      first report of an aroQ mutant of a bacterial pathogen, and the results may have
      implications for the construction of aromatic mutants of Mycobacterium
      tuberculosis for use as vaccines.

PMID- 9234751
TI  - B7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme
      arthritis.
AB  - We assessed the role of B7-1 and B7-2 costimulatory molecules on the course of
      murine Lyme borreliosis because experimental Lyme arthritis is dependent, at
      least partially, upon the development of the host immune response and these
      costimulatory molecules have been implicated in CD4+ T-cell differentiation. We
      demonstrated that Borrelia burgdorferi infection upregulated the surface
      expression of B7-1 and B7-2 in macrophages and B7-2 expression in B cells. Anti
      B7-2 monoclonal antibody (MAb) or both anti-B7-2 and anti-B7-1 MAbs produced a
      dose-dependent increase in the severity of Lyme arthritis in C3H/HeN mice. In
      contrast, the administration of an anti-B7-1 MAb reduced the degree of arthritis.
      These effects occurred independently of significant alteration in B. burgdorferi
      specific immune responses, including splenocyte proliferative responses to B.
      burgdorferi, B. burgdorferi antibody levels and specificity, and mRNA levels of
      gamma interferon, interleukin-4 (IL-4), IL-10, and IL-12 in the spleen. These
      results demonstrate that signaling delivered by B7-1 and B7-2 plays a role in
      determining the severity of acute murine Lyme arthritis.

PMID- 9234754
TI  - Genetic control of antibody responses induced by recombinant Mycobacterium bovis
      BCG expressing a foreign antigen.
AB  - Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a
      promising candidate for the development of future vaccines and was shown in
      several experimental models to induce protective immunity against bacterial or
      parasitic infections. Innate resistance to BCG infection is under genetic control
      and could modify the immune responses induced against an antigen delivered by
      such engineered microorganisms. To investigate this question, we analyzed the
      immune responses of various inbred strains of mice to recombinant BCG expressing
      beta-galactosidase. These experiments demonstrated that BALB/c mice developed
      strong antibody responses against BCG expressing beta-galactosidase under the
      control of two different promoters. In contrast, C57BL/6, C3H, and CBA mice
      produced high anti-beta-galactosidase antibody titers only when immunized with
      recombinant BCG expressing beta-galactosidase under the control of the pblaF*
      promoter, which induced the production of high levels of this antigen. This
      difference in mouse responsiveness to recombinant BCG was not due to innate
      resistance to BCG infection, since similar immune responses were induced in
      Ity(r) and Ity(s) congenic strains of mice. In contrast, the analysis of anti
      beta-galactosidase antibody responses of H-2 congenic mice in two different
      genetic backgrounds demonstrated that H-2 genes are involved in the immune
      responsiveness to beta-galactosidase delivered by recombinant BCG. Together,
      these results demonstrate that immune responses to an antigen delivered by
      recombinant BCG are under complex genetic influences which could play a crucial
      role in the efficiency of future recombinant BCG vaccines.

PMID- 9234755
TI  - Mouse strain-dependent variation in the course and outcome of chlamydial genital
      tract infection is associated with differences in host response.
AB  - Whether there is a pathogenic or protective outcome to chlamydial infection may
      be defined by the host response. We infected C57BL/6 (C57) and C3H/HeN (C3H) mice
      with the human biovar of Chlamydia trachomatis, serovar E, and, in select
      experiments, with the mouse pneumonitis agent of C. trachomatis (MoPn). We
      compared the courses of infection, histopathology, and host responses that
      resulted from these infections. The duration of infection with either chlamydial
      biovar was significantly increased in the C3H strain of mice. The intensity of
      infection was examined in mice infected with serovar E, and it was significantly
      increased in the C3H strain. Histopathology revealed the incidence of severe
      hydrosalpinx to be significantly greater in C3H mice than in C57 mice. In
      contrast, severe distention of the uterine horns was observed in all infected C57
      mice compared to none of the C3H mice infected with serovar E and only 25% of
      those infected with MoPn. Acute inflammation was significantly increased in the
      uterine horns of C57 mice compared to that of C3H mice. Examination of antigen
      specific responses revealed qualitatively similar responses in the two strains.
      Determination of gamma interferon- versus interleukin 4- producing cells revealed
      the predominance of a Th1 response in both strains. Serum enzyme-linked
      immunosorbent assays for immunoglobulin G1 (IgG1) and IgG2a revealed a
      predominance of IgG2a antibody in both strains, although the levels of antibody
      were significantly greater in C3H mice. Lymphocyte proliferation studies revealed
      increased proliferation in the iliac nodes of both strains at 1 to 3 weeks after
      infection. Because of the early eradication of infection observed in the C57
      strain, we explored the relative production of tumor necrosis factor alpha (TNF
      alpha) in the two strains. TNF-alpha levels were significantly increased in the
      genital tract secretions of C57 mice compared to that of C3H mice during the
      first week of infection. Increased TNF-alpha may be beneficial to the host by
      leading to earlier eradication of infection, thereby preventing infection of the
      oviduct and thus the major disease sequelae associated with chlamydial infection
      of the genital tract.

PMID- 9234756
TI  - Gut intraepithelial lymphocytes induce immunity against Cryptosporidium infection
      through a mechanism involving gamma interferon production.
AB  - Immunological control of infection with cryptosporidia in mice is dependent on
      CD4+ T cells and the production of gamma interferon (IFN-gamma), but to date, the
      mucosal T cells which produce IFN-gamma local to the infection have not been
      characterized. We previously showed that immunity against the gastric parasite
      Cryptosporidium muris could be adoptively transferred to adult SCID (severe
      combined immunodeficiency) mice with small intestinal intraepithelial lymphocytes
      (IEL) from previously infected immunocompetent mice, but only if the donor CD4+ T
      cells were intact. The present investigation examined whether IFN-gamma was
      important in the effector mechanisms mediated by immune IEL in SCID mice. The
      development of resistance against C. muris infection in SCID mice given immune
      IEL was prevented by treatment with a hamster anti-mouse IFN-gamma-neutralizing
      monoclonal antibody, but following cessation of antibody treatment, the mice
      recovered from infection. In further experiments, an enzyme-linked immunospot
      (ELISPOT) technique was used to compare frequencies of IFN-gamma-producing cells
      in activated T-cell populations from C. muris-immune and naive donor mice.
      Stimulation with concanavalin A or a rat anti-mouse CD3 monoclonal antibody
      resulted in detection of greater numbers of cells producing IFN-gamma from immune
      than naive IEL populations. Small numbers of IEL from C. muris-immune mice, but
      not from naive mice, also produced IFN-gamma when cultured with soluble oocyst
      antigen, but this occurred only if gamma-irradiated spleen cells were cocultured
      with the immune IEL. These results suggested that IEL were important in the
      generation of immunity to Cryptosporidium and that one of their crucial functions
      was to produce IFN-gamma at the site of infection.

PMID- 9234757
TI  - Genetic diversity among clinical and environmental isolates of Aspergillus
      fumigatus.
AB  - To determine if cases of invasive aspergillosis (IA) were caused by strains of
      Aspergillus fumigatus with unique characteristics, strains from immunosuppressed
      patients with IA were compared to strains obtained from sputa of patients with
      cystic fibrosis and to strains from the environment. An extremely high genomic
      diversity was observed among the 879 strains typed by Southern blotting with a
      retrotransposon-like element from A. fumigatus (C. Neuveglise, J. Sarfati, J. P.
      Latge, and S. Paris, Nucleic Acids Res. 24:1428-1434, 1996). Analysis of Southern
      blot hybridization patterns showed the absence of clustering between
      environmental isolates and clinical isolates from patients with IA or cystic
      fibrosis. In addition, strains could not be clustered depending on their
      geographical location. This study implies that practically any strain of A.
      fumigatus is potentially pathogenic and can provoke a case of IA when it
      encounters a favorable environment in an immunosuppressed host.

PMID- 9234758
TI  - Contribution of proteases and LasR to the virulence of Pseudomonas aeruginosa
      during corneal infections.
AB  - The roles of the Pseudomonas aeruginosa proteases LasB (elastase) and LasA and
      the transcriptional activator LasR, which regulates the expression of these
      proteases, were evaluated in a murine model of P. aeruginosa corneal infection.
      In scarified corneas, P. aeruginosa PAO-A1 (LasA negative) or PAO-B1A1 (LasB and
      LasA negative) at a dose of 10(8) CFU per eye caused very mild or no disease
      following infection; however, the defect in PAO-A1 could not be complemented by
      supplying a functional copy of lasA either on a plasmid or inserted into the
      chromosome. In contrast, PAO-B1 (LasB negative) colonized the cornea and caused
      disease equal in severity to disease caused by the parental strain, PAO1-I.
      Although LasR is a known regulator of lasA expression, PAO-R1, a lasR-negative
      derivative of PAO1-I, was as virulent as the parental strain during corneal
      infection. When transcriptional fusion plasmids were used to quantify the
      expression of the lasB and lasA genes in P. aeruginosa PAO1-I and PAO-R1, the
      lasB::lacZ fusion in PAO-R1 showed only 3.5% as much activity as it did in PAO1
      I, while the activity of the lasA::lacZ fusion in PAO-R1 was 27.8% of that in
      PAO1-I. Coadministration of 5 microg of purified LasA protease with PAO-A1 did
      not reconstitute a wild-type infection. This treatment produced an acute toxic
      reaction leading to prolonged eyelid closure without inflammatory destruction of
      the cornea that was similar to that observed when LasA was administered alone.
      These results indicate that insertional inactivation of lasA renders P.
      aeruginosa avirulent in a murine model of keratitis and that neither LasR nor
      elastase production is required for the establishment and maintenance of corneal
      infection. However, the lack of virulence of the LasA-deficient strains cannot be
      ascribed with certainty to the deficiency of LasA from the available data.

PMID- 9234759
TI  - The anthrax toxin activator gene atxA is associated with CO2-enhanced non-toxin
      gene expression in Bacillus anthracis.
AB  - The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a
      regulon, in which transcription of all three genes is activated in trans by the
      same regulatory gene, atxA, in response to the same signal, CO2. In atxA+
      strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5%
      CO2 relative to cells grown in air. CO2-enhanced toxin gene transcription is not
      observed in atx4-null mutants. Here, we used two independent techniques to obtain
      evidence for additional CO2-induced atxA-regulated genes. First, total protein
      preparations from atxA4+ and atxA isolates grown in 5% CO2 and in air were
      examined by two-dimensional electrophoresis. Comparison of the resulting protein
      patterns indicated that synthesis of non-toxin proteins is influenced by growth
      in elevated CO2 and the toxin gene regulator, atxA. Second, we generated random
      transcriptional lacZ fusions in B. anthracis with transposon Tn917-LTV3.
      Transposon-insertion libraries were screened for mutants expressing CO2-enhanced
      atxA-dependent beta-galactosidase activity. DNA sequence analysis of transposon
      insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed
      10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which
      did not map to the toxin genes. The tcr-lacZ fusion mutants (tcr for toxin
      coregulated) were Tox+, indicating that these genes may not be involved in
      anthrax toxin gene activation. Our data indicate a clear association of atxA with
      CO2-enhanced gene expression in B. anthracis and provide evidence that atxA
      regulates genes other than the structural genes for the anthrax toxin proteins.

PMID- 9234760
TI  - Effects of Ixodes scapularis and Borrelia burgdorferi on modulation of the host
      immune response: induction of a TH2 cytokine response in Lyme disease-susceptible
      (C3H/HeJ) mice but not in disease-resistant (BALB/c) mice.
AB  - Previous studies have demonstrated that both Ixodes scapularis saliva and
      Borrelia burgdorferi antigens modulated lymphokines and monokines in vitro. The
      studies presented here were designed to delineate the role of I. scapularis and
      B. burgdorferi in modulation of the host immune response in vivo. Infestation of
      C3H/HeJ mice with infected I. scapularis resulted in an up regulation of IL-4 as
      early as 8 days after tick infestation, while the levels of T helper cell type 1
      (TH1) cytokines, interleukin-2 (IL-2) and gamma interferon (IFN-gamma), were
      significantly decreased by days 10 to 12. In contrast, the cytokine profile of
      BALB/c mice exposed to infected nymphal ticks resulted in only transient
      alterations in IL-4, IL-2, and IFN-gamma production throughout a 12-day period
      postinfestation. Although the IL-10 level was elevated in both C3H/HeJ and BALB/c
      mice infested with infected nymphal ticks, no significant difference in the
      levels of IL-10 was noted between the mouse strains. Flow-cytometric analysis
      demonstrated increases in the numbers of splenic B-cell and CD4+ lymphocytes in
      C3H/HeJ but not BALB/c mice exposed to infected ticks. Cell depletion experiments
      with C3H/HeJ mice demonstrated that CD4+ cells were the sole producers of IFN
      gamma and IL-10 while both CD4+ and CD8+ splenocytes contributed to the
      production of IL-2 and IL-4. These findings suggest that B and CD4+ splenocytes
      are activated, increase in number, and produce a polarized TH2 response in
      C3H/HeJ mice exposed to infected I. scapularis. Given that C3H/HeJ mice are
      susceptible to Lyme disease and the initial TH2 polarization is not evident in
      BALB/c mice, effective control of this response may have ramifications for
      spirochete transmission in vivo.

PMID- 9234761
TI  - T-helper-cell cytokines in the early evolution of murine Lyme arthritis.
AB  - Genetic susceptibility to murine Lyme arthritis has been correlated with the
      dominance of T-helper (Th1)- or Th2-cell-associated cytokines. To determine when
      commitment of the Th cell phenotype occurs, we examined the kinetics of gamma
      interferon (IFN-gamma) and interleukin-4 (IL-4) production by lymph node T cells
      of disease-susceptible C3H/HeN and disease-resistant BALB/c mice from days 2
      through 30 of infection, a period encompassing the evolution of disease and early
      regression. BALB/c mice produced more IFN-gamma on day 2 of infection than did
      C3H/HeN mice, whereas IL-4 was first detected on day 14. In contrast, only IFN
      gamma could be detected in C3H/HeN mice, and the levels steadily increased from
      day 2 to surpass those seen in BALB/c mice by day 14 of infection. Despite the
      difference in cytokine profiles, both BALB/c and C3H/HeN mice developed
      comparable arthritis assessed at 14 days of infection. Arthritis regressed by day
      30 in BALB/c mice but persisted in C3H/HeN mice. These studies are the first to
      demonstrate that the Th2 response to Borrelia burgdorferi infection of BALB/c
      mice is preceded by a Th1 cytokine response. Moreover, the timing of the
      appearance of IL-4 suggests that its primary effect is not in preventing disease,
      as suggested by others, but, rather, in hastening the resolution of inflammation.
      The implications of these findings for the orchestration of host defense against
      B. burgdorferi infection are discussed.

PMID- 9234762
TI  - Cloning, characterization, and chromosomal mapping of a phospholipase
      (lecithinase) produced by Vibrio cholerae.
AB  - Phospholipases are associated with virulence in bacterial diseases. Vibrio
      cholerae produces a phospholipase (lecithinase), with enzyme production
      visualized as a zone of clearing around colonies plated on egg yolk agar. The
      role of phospholipase in gut colonization or disease pathogenesis is unknown. We
      used the egg yolk agar assay to clone and characterize a gene encoding a
      phospholipase from V. cholerae El Tor strain E7946. Sequence analysis revealed a
      1,254-bp open reading frame (lec) encoding a 418-amino-acid protein with a
      predicted molecular weight of 47,600. The predicted sequence exhibits DNA
      homology to other Vibrionaceae phospholipases. A potential signal sequence exists
      in the predicted amino acid sequence, as does a lipid binding motif found in
      prokaryotic and eukaryotic phospholipases and lipases. Polyacrylamide gel
      electrophoresis combined with an egg yolk agarose overlay demonstrated
      phospholipase activity migrating at a relative molecular weight of 45,000 in
      preparations of V. cholerae and the Escherichia coli clone. Restriction mapping
      and Southern blot analysis revealed that lec, hlyA (hemolysin), and hlyC (lipase)
      are adjacent on the V. cholerae chromosome, and chromosomal digests of several El
      Tor, classical, and O139 (Bengal) strains demonstrated conservation of this gene
      arrangement. An in-frame internal deletion of the lec gene was constructed and
      recombined into the chromosome of attenuated V. cholerae El Tor strain CVD 110.
      The resulting mutant lacked lecithinase activity on egg yolk agar but had
      undiminished reactivity in rabbit ligated ileal loop assays.

PMID- 9234763
TI  - Oral immunization with attenuated vaccine strains of Vibrio cholerae expressing a
      dodecapeptide repeat of the serine-rich Entamoeba histolytica protein fused to
      the cholera toxin B subunit induces systemic and mucosal antiamebic and anti-V.
      cholerae antibody responses in mice.
AB  - Entamoeba histolytica is a significant cause of morbidity and mortality
      worldwide. The serine-rich E. histolytica protein (SREHP) is a surface-expressed
      trophozoite protein that includes multiple hydrophilic tandem repeats. A purified
      fusion protein between the dodecapeptide repeat of SREHP and cholera toxin B
      subunit (CTB) has previously been shown to be immunogenic in mice after oral
      inoculation when cholera toxin is coadministered as an immunoadjuvant. We
      engineered a live attenuated El Tor Vibrio cholerae vaccine strain, Peru2, to
      express the SREHP-12-CTB fusion protein to the supernatant from either a plasmid
      [Peru2 (pETR5.1)] or from a chromosomal insertion (ETR3). Vector strains were
      administered orally to germfree mice that were subsequently housed under
      nongermfree conditions; mice received one (day 0) or two (days 0 and 14)
      inoculations. No immunoadjuvant or cholera holotoxin was administered. Mice that
      received two inoculations of Peru2(pETR5.1) had the most pronounced antiamebic
      systemic and mucosal immunologic responses. Less marked, but significant, anti
      SREHP serum immunoglobulin G antibody responses were also induced in mice that
      received either one or two oral inoculations of strain ETR3. Anti-V. cholerae
      responses were also induced, as measured by the induction of serum vibriocidal
      antibodies and by serum and mucosal anti-CTB antibody responses. These results
      suggest that V. cholerae vector strains can be successful delivery vehicles for
      the SREHP-12-CTB fusion protein, to induce mucosal and systemic antiamebic and
      anti-V. cholerae immune responses. The magnitude of these responses is
      proportional to the amount of SREHP-12-CTB produced by the vector strain.

PMID- 9234764
TI  - Inflammatory bowel disease: an immunity-mediated condition triggered by bacterial
      infection with Helicobacter hepaticus.
AB  - Inflammatory bowel disease (IBD) is thought to result from either an abnormal
      immunological response to enteric flora or a normal immunological response to a
      specific pathogen. No study to date has combined both factors. The present
      studies were carried out with an immunologically manipulated mouse model of IBD.
      Mice homozygous for the severe combined immunodeficiency (scid) mutation develop
      IBD with adoptive transfer of CD4+ T cells expressing high levels of CD45RB
      (CD45RB(high) CD4+ T cells). These mice do not develop IBD in germfree
      conditions, implicating undefined intestinal flora in the pathogenesis of
      lesions. In controlled duplicate studies, the influence of a single murine
      pathogen, Helicobacter hepaticus, in combination with the abnormal immunological
      response on the development of IBD was assessed. The combination of H. hepaticus
      infection and CD45RB(high) CD4+ T-cell reconstitution resulted in severe disease
      expression similar to that observed in human IBD. This study demonstrates that
      IBD develops in mice as a consequence of an abnormal immune response in the
      presence of a single murine pathogen, H. hepaticus. The interaction of host
      immunity and a single pathogen in this murine system provides a novel model of
      human IBD, an immunity-mediated condition triggered by bacterial infection.

PMID- 9234765
TI  - Identification and characterization of a metalloprotease activity from
      Helicobacter pylori.
AB  - Helicobacter pylori produces a metalloprotease with a native molecular size of
      approximately 200 kDa, as determined by size-exclusion chromatography.
      Subcellular distribution studies demonstrated that the activity was associated
      with the outer membrane fraction of the bacterium. In addition, the protease was
      secreted by the bacterium when grown in liquid culture. The enzyme activity was
      measured by hydrolysis of azocasein and biotinylated casein and exhibited optimal
      caseinolytic activity at pH 8.0 (37 degrees C). The activity was inhibited by
      EDTA, 1,10-phenanthroline, phosphoramidon, pyridine-2,6-dicarboxylic acid, and 8
      hydroxyquinoline-5-sulfonic acid (HQSA). Inhibition by HQSA was reversed by zinc,
      whereas inhibition due to EDTA was reversed by excess calcium, thus indicating
      that the enzyme was a zinc-dependent, calcium-stabilized endoproteinase.
      Furthermore, titration with Zn2+ of a desalted, active-site zinc-chelated
      preparation of the protease demonstrated that Zn2+ was essential for activity.
      Leupeptin, phenylmethylsulfonyl fluoride, E-64, pepstatin A, dithiothreitol, and
      2-mercaptoethanol had no effect on enzymatic activity. Addition of Ca2+ or Mg2+
      to the incubation medium resulted in approximately a twofold stimulation of the
      azocaseinolytic activity of the enzyme. The protease was stably expressed since
      it was active even after repeated subculture of the bacterium. Bovine serum
      albumin, hide powder azure, and elastin-Congo red remained intact even after
      prolonged exposure to the enzyme. The surface expression of this metalloprotease
      activity raises the possibility that this enzyme may be involved in the
      proteolysis of a variety of host proteins in vivo and thereby contributes to
      gastric pathology.

PMID- 9234766
TI  - Protective immunity against Plasmodium yoelii malaria induced by immunization
      with particulate blood-stage antigens.
AB  - The Plasmodium yoelii murine model was used to test several combinations of blood
      stage antigens and adjuvants for the ability to induce immunity to blood-stage
      malaria. Upon fractionation of whole blood-stage antigen into soluble and
      insoluble components, only the particulate antigens (pAg) induced protective
      immune responses. Of a number of adjuvants tested, Quil A was the most effective.
      Immunization with pAg plus Quil A induced solid protection against nonlethal and
      lethal P. yoelii challenge infection. Analysis of cytokine production revealed
      mRNA for Th1-type cytokines (interleukin 2 [IL-2] and gamma interferon) as well
      as Th2-type cytokines (IL-4 and IL-10) in the spleens of both protected and
      susceptible animals. The data suggested that the protective pAg response was
      associated with the earlier production of cytokine mRNA with a Th2 phenotype
      somewhat favored. Immunization of B-cell-deficient JHD mice indicated that the
      protection against P. yoelii induced by pAg immunization was B cell dependent.
      Although immunization with pAg plus Quil A increased the levels of antigen
      specific antibodies of all four immunoglobulin G (IgG) isotypes, protection
      correlated most closely with the presence of IgG1 and IgG2b antibodies. Sera from
      pAg-plus-Quil A-immunized animals recognized only a limited subset of six to
      eight distinct P. yoelii antigens, primarily associated with the pAg fraction.
      These results provide the basis for the identification and characterization of
      potential vaccine antigens, selected solely for their ability to immunize against
      blood-stage malaria.

PMID- 9234767
TI  - OspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks.
AB  - Ixodes ticks are infected by Borrelia burgdorferi when larvae feed on spirochete
      infected mice. We studied the acquisition of B. burgdorferi by larval ticks,
      characterized the production of outer surface protein A (OspA) by spirochetes
      entering larvae, and examined the effects of OspA antibodies on the establishment
      of B. burgdorferi infections in ticks. Most larvae were infected by spirochetes
      24 to 48 h after placement on mice. OspA antibodies stained the first spirochetes
      observed in larvae, suggesting that OspA is synthesized early during the
      colonization of the vector. When OspA antibodies were administered to B.
      burgdorferi-infected mice and larvae were then placed on the animals, the
      severity of larval infection and the number of infected ticks (7 of 16) were
      decreased compared with that of controls (15 of 16). The inhibitory effects of
      OspA antibodies were observed with passive antibody transfer as well as active
      host-generated immunity. The lower larval infection rate observed in the presence
      of OspA antibodies was exacerbated after the larval molt since only 1 of 12
      nymphs was infected, and none of the mice that were fed upon by these nymphs
      became infected with B. burgdorferi. Therefore, an OspA antibody response in mice
      altered the reservoir competence of the vertebrate host by inhibiting the
      movement of B. burgdorferi from the host to the vector.

PMID- 9234768
TI  - Structurally defined epitopes of Haemophilus ducreyi lipooligosaccharides
      recognized by monoclonal antibodies.
AB  - By use of enzyme-linked immunosorbent assay and immunoblotting techniques, the
      migration patterns and binding epitopes of lipooligosaccharides (LOS) from 10
      Haemophilus ducreyi strains were investigated with two monoclonal antibodies
      (MAbs), MAHD6 and MAHD7, raised against LOS from H. ducreyi ITM 2665. Closely
      related LOS, with defined structures, from Haemophilus influenzae, Bordetella
      pertussis, Aeromonas spp., and synthetic glycoproteins were also included in the
      analyses. The MAbs bound to conserved epitopes of LOS exposed on the surface of
      H. ducreyi. The MAb MAHD6 reacted with 8 of the 10 LOS from H. ducreyi but with
      none of the other Haemophilus or Bordetella spp. with structurally defined LOS.
      It is suggested that MAb MAHD6 binds to a LOS epitope (-DD-Hepp-1-->6-beta-D-Glcp
      ). This LOS epitope is not present in the hexasaccharide structure of LOS from H.
      ducreyi ITM 4747 (E. K. H. Schweda, A. C. Sundstrom, L. M. Eriksson, J. A.
      Jonasson, and A. A. Lindberg, J. Biol. Chem. 269:12040-12048, 1994). Because MAb
      MAHD6 reacts with the epitope mentioned above, it also discriminates between the
      two LOS structures, the hexasaccharide group and the nonasaccharide group, of H.
      ducreyi strains. MAb MAHD7 recognizes the common conserved inner core region of
      the LOS because it reacts with all H. ducreyi strains and with LOS with minor
      components in the inner core epitope structure. Rabbit polyclonal sera raised
      against the LOS from strains CCUG 4438 and CCUG 7470 were tested with the 10 LOS
      from the H. ducreyi strains. The antiserum to CCUG 7470 reacted with all H.
      ducreyi strains as did MAb MAHD7, whereas the antiserum to CCUG 4438 reacted with
      only its homologous strain and strain ITM 4747. Also, the LOSs of our reference
      strains CCUG 4438 and CCUG 7470 were structurally analyzed by use of sugar
      analyses and electrospray ionization-mass spectrometry. The hexasaccharide and
      nonasaccharide structures obtained from LOS of strains CCUG 4438 and CCUG 7470
      were identical to the described LOS structures from H. ducreyi ITM 4747 and ITM
      2665, respectively. In conclusion, the MAb MAHD6 recognizes an epitope present in
      the nonasaccharide LOS group, whereas the MAb MAHD7 recognizes a conserved
      epitope on LOS of H. ducreyi, which is present in all strains of H. ducreyi
      tested. Two major groups of oligosaccharides were distinguished by their LOS
      structures and the reactivity of monoclonal as well as polyclonal antibodies. The
      majority of H. ducreyi strains possess a nonasaccharide structure of LOS.

PMID- 9234769
TI  - Active sites of salivary proline-rich protein for binding to Porphyromonas
      gingivalis fimbriae.
AB  - Porphyromonas gingivalis fimbriae specifically bind salivary acidic proline-rich
      protein 1 (PRP1) through protein-protein interactions. The binding domains of
      fimbrillin (a subunit of fimbriae) for PRP1 were analyzed previously (A. Amano,
      A. Sharma, J.-Y. Lee, H. T. Sojar, P. A. Raj, and R. J. Genco, Infect. Immun.
      64:1631-1637, 1996). In this study, we investigated the sites of binding of the
      PRP1 molecules to the fimbriae. PRP1 (amino acid residues 1 to 150) was
      proteolysed to three fragments (residues 1 to 74 [fragment 1-74], 75 to 129, and
      130 to 150). 125I-labeled fimbriae clearly bound fragments 75-129 and 130-150,
      immobilized on a polyvinylidene difluoride membrane; both fragments also
      inhibited whole-cell binding to PRP1-coated hydroxyapatite (HAP) beads by 50 and
      83%, respectively. However, the N-terminal fragment failed to show any effect.
      Analogous peptides corresponding to residues 75 to 89, 90 to 106, 107 to 120, 121
      to 129, and 130 to 150 of PRP1 were synthesized. The fimbriae significantly bound
      peptide 130-150, immobilized on 96-well plates, and the peptide also inhibited
      binding of 125I-labeled fimbriae to PRP1-coated HAP beads by almost 100%.
      Peptides 75-89, 90-106, and 121-129, immobilized on plates, showed considerable
      ability to bind fimbriae. For further analysis of active sites in residues 130 to
      150, synthetic peptides corresponding to residues 130 to 137, 138 to 145, and 146
      to 150 were prepared. Peptide 138-145 (GRPQGPPQ) inhibited fimbrial binding to
      PRP1-coated HAP beads by 97%. This amino acid sequence was shared in the
      alignment of residues 75 to 89, 90 to 106, and 107 to 120. Six synthetic peptides
      were prepared by serial deletions of individual residues from the N and C termini
      of peptide GRPQGPPQ. Peptide PQGPPQ was as inhibitory as peptide GRPQGPPQ.
      Further deletions of the dipeptide Pro-Gln from the N and C termini of peptide
      PQGPPQ resulted in significant loss of the inhibitory effect. These results
      strongly suggest that PQGPPQ is the minimal active segment for binding to P.
      gingivalis fimbriae and that the moiety of the Pro-Gln dipeptide plays a critical
      role in expressing binding ability.

PMID- 9234770
TI  - Nonspecific immune responses and mechanisms of resistance to Eimeria papillata
      infections in mice.
AB  - Severe combined immunodeficient (SCID)-beige mice inoculated with the
      intracellular parasite Eimeria papillata produced significantly more oocysts
      during primary infections than inoculated immunodeficient SCID mice. Therefore,
      the addition of the beige mutation, which detrimentally affects neutrophil and
      natural killer (NK) cell functions, enhanced the parasites' ability to reproduce
      within the small intestine. To identify which of these two cell types is
      responsible for a protective immune response during primary infection, the
      following groups of mice were inoculated: (i) SCID mice depleted of neutrophils
      with antigranulocyte monoclonal antibody (RB6-8C5), (ii) C57BL/6 mice depleted of
      NK cells with the anti-NK-1.1 monoclonal antibody (PK136), and (iii) transgenic
      Tg epsilon26++ mice (T and NK cell deficient). To identify the mechanisms of
      immunity during primary and secondary infections, gamma interferon (IFN-gamma)
      knockout and perforin knockout mice were inoculated. Oocyst output was found to
      be significantly higher during primary infection for mice depleted of NK cells by
      administration of anti-NK-1.1 antibodies, for Tg epsilon26++ mice, and for IFN
      gamma knockout mice. During secondary infections, only perforin knockout mice
      produced significantly more oocysts compared to control mice. Our observations
      suggest that NK cells inhibit E. papillata oocyst output during primary infection
      by the production of IFN-gamma and that this inhibition is independent of
      perforin. Immunity to reinfection does not require IFN-gamma but appears to be
      mediated, at least in part, by a perforin-dependent mechanism.

PMID- 9234771
TI  - Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia
      enhances phagocytosis and killing by human neutrophils and alveolar macrophages.
AB  - To determine whether the lung surfactant proteins A (SP-A) and D (SP-D) are
      involved in the initial protective immunity against opportunistic pulmonary
      fungal infections caused by Aspergillus fumigatus, we performed a series of in
      vitro functional studies to see if SP-A and SP-D enhanced binding, phagocytosis,
      activation, and killing of A. fumigatus conidia by human alveolar macrophages and
      circulating neutrophils. Both SP-A and SP-D bound to carbohydrate structures on
      A. fumigatus conidia in a calcium-dependent manner. SP-A and SP-D were also
      chemoattractant and significantly enhanced agglutination and binding of conidia
      to alveolar macrophages and neutrophils. Furthermore, in the presence of SP-A and
      SP-D, the phagocytosis, oxidative burst, and killing of A. fumigatus conidia by
      neutrophils were significantly increased. These findings indicate that SP-A and
      SP-D may have an important immunological role in the early antifungal defense
      responses in the lung, through inhibiting infectivity of conidia by agglutination
      and by enhancing uptake and killing of A. fumigatus by phagocytic cells.

PMID- 9234772
TI  - Glycosphingolipid-binding protein of Borrelia burgdorferi sensu lato.
AB  - The binding of Borrelia burgdorferi, the causative agent of Lyme disease, to
      glycosphingolipids present in various types of cells was examined. B. burgdorferi
      bound specifically to galactosylceramide (GalCer) and glucosylceramide (GlcCer)
      but not to other glycosphingolipids, as determined by a thin-layer chromatography
      (TLC) overlay assay. The binding specificity of B. burgdorferi to various
      glycosphingolipids suggested that the binding receptor in this species is
      ceramide monohexoside. The levels of binding of B. burgdorferi virulent strain
      297 to GlcCer, sulfatide, lactosylceramide, and galactosylgloboside were 56.2,
      1.6, 15.9, and 9.7%, respectively, relative to that to GalCer. Virulent low
      passage strains of B. burgdorferi were serially subcultured in BSK II medium, and
      the resultant high-passage strains were not capable of infecting mice and did not
      induce footpad swelling. The levels of binding of the low-passage strains to
      GalCer on TLC plates and to CHO-K1 cells in vitro were threefold higher than
      those of high-passage strains. Binding was not affected by pretreatment of
      Borrelia with monospecific anti-outer surface protein C (OspC) antiserum. These
      results indicated that the binding of Borrelia to glycosphingolipid expressed on
      the cell surface plays an essential role in infection of mammalian hosts.
      However, OspC was not associated with binding. The necessity of the sugar and N
      acyl moieties in GalCer for the binding of Borrelia was shown by a TLC overlay
      assay using chemically modified GalCer. Furthermore, three proteins, 67-kDa
      protein, 62-kDa Hsp60, and 41-kDa flagellin, were involved in binding of B.
      burgdorferi to GalCer, as shown by blotting assay using biotinylated GalCer as a
      probe.

PMID- 9234774
TI  - Evaluation of bacterial survival and phagocyte function with a fluorescence-based
      microplate assay.
AB  - To compare antibacterial function in macrophages from mice deficient in the
      respiratory burst oxidase or inducible nitric oxide synthase, we developed a
      fluorescence-based microplate assay of bacterial survival. As bacteria grow, they
      convert a formulation of resazurin termed AlamarBlue from its nonfluorescent
      oxidized state to its fluorescent reduced state. The time required to achieve a
      given fluorescence is inversely proportional to the number of viable bacteria
      present when the dye is added. This relationship allows a precise, accurate
      assessment of bacterial numbers with greater sensitivity and throughput and at
      less cost than conventional assays. The assay facilitated quantification of the
      killing of Escherichia coli by S-nitrosoglutathione and hydrogen peroxide and of
      Salmonella typhimurium by human neutrophils and mouse macrophages. Mouse
      macrophages lacking the 91-kDa subunit of the respiratory burst oxidase were
      deficient in their ability to kill S. typhimurium, while those lacking inducible
      nitric oxide synthase were unimpaired.

PMID- 9234773
TI  - Intracellular Salmonella dublin induces substantial secretion of the 40
      kilodalton subunit of interleukin-12 (IL-12) but minimal secretion of IL-12 as a
      70-kilodalton protein in murine macrophages.
AB  - The induction by intracellular pathogens of interleukin-12 (IL-12) secretion is
      of particular importance since this cytokine has been shown to be necessary for
      optimal cell-mediated immune responses. Several recent investigations have
      suggested that cultured macrophages are a significant source of IL-12 following
      intracellular infection with pathogens such as Salmonella spp. In an effort to
      critically evaluate the magnitude of the IL-12 response in cultured macrophages
      following interaction with Salmonella dublin, enzyme-linked immunosorbent assays
      specific for the 40- and 70-kDa subunits of IL-12 (IL-12p40 and IL-12p70) and a
      sensitive bioassay for IL-12p70 were used. Using BALB/c macrophages, S. dublin at
      various challenge doses was a potent inducer of IL-12p40 secretion (>6,000
      pg/10(7) macrophages). However when secretion of IL-12p70 was evaluated, S.
      dublin did not induce comparable IL-12p70 production (<80 pg/10(7) macrophages)
      at any time, despite varying the challenge dose of Salmonella. The limited
      ability of BALB/c (Ity(s)) macrophages to secrete IL-12p70 in response to
      Salmonella was not a strain-specific phenomenon since similar results were
      demonstrated for macrophages isolated from CBA/J (Ity(r)) and C3H/HeJ
      (lipopolysaccharide [LPS]-hyporesponsive) mice. While intracellular infection
      with Salmonella was not a potent stimulus for IL-12p70 secretion in these mouse
      strains, macrophages from these mice responded significantly to a stimulus of
      gamma interferon plus LPS. Taken together these results demonstrate a limited
      capacity for intracellular Salmonella to stimulate murine macrophage secretion of
      IL-12p70, despite being a significant stimulus for IL-12p40 secretion.
      Furthermore, our results suggest that Salmonella-induced IL-12p40 secretion by
      macrophages is not solely an LPS-mediated event.

PMID- 9234775
TI  - Activation of the interleukin-1beta precursor by Treponema denticola: a potential
      role in chronic inflammatory periodontal diseases.
AB  - There are several indications suggesting that interleukin-1beta (IL-1beta) may
      play an important role in inflammatory periodontal diseases. We hypothesized that
      periodontal sites would represent a unique combination of both cellular sources
      of IL-1beta precursor (pro-IL-1beta) and microbial proteases and proposed that
      Treponema denticola, a suspected periodontal pathogen, would play a critical role
      in the inflammatory nature of adult chronic periodontitis by activating pro-IL
      1beta. The aim of this study was thus to demonstrate the proteolytic cleavage and
      activation of the inactive precursor pro-IL-1beta by T. denticola. After
      incubation of bacterial cells with recombinant pro-IL-1beta, proteolytic cleavage
      was monitored by Western immunoblotting, and the biological activity of the
      digestion products was tested in a bioassay. We report here that T. denticola can
      cleave pro-IL-1beta to yield two fragments with molecular masses of 18 and 19
      kDa. Cleavage products showed a dose-dependent biological activity in the
      thymocyte proliferation bioassay, and this activity was inhibited by anti-IL
      1beta neutralizing antibodies. These results suggest that T. denticola may have a
      proinflammatory role in periodontal diseases.

PMID- 9234776
TI  - Neisserial porins may provide critical second signals to polysaccharide-activated
      murine B cells for induction of immunoglobulin secretion.
AB  - Resting B cells stimulated with dextran-conjugated anti-immunoglobulin D (anti
      IgD) antibodies (anti-Ig-dex), a model for B-cell activation in response to
      polysaccharide antigens, proliferate but secrete little if any Ig, unless
      additional stimuli are present. In order to elucidate the parameters which
      costimulate T-cell-independent antipolysaccharide antibody responses during
      bacterial infections, we tested the capacities of highly purified porin proteins
      from Neisseria meningitidis and Neisseria gonorrhoeae to augment in vitro
      proliferation and induce Ig secretion by anti-Ig-dex-activated B cells. Resting B
      cells, from lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice, proliferated and
      secreted IgM in response to each of three distinct porins acting alone. Further,
      porins, even at concentrations that were minimally inductive when acting alone,
      were strongly synergistic with anti-Ig-dex for proliferation and Ig secretion.
      Similar synergistic effects of porins with CD40-ligand were also observed. These
      effects of porins were shown to occur directly at the level of the B cell. The
      predominant Ig isotype elicited in response to porins plus anti-Ig-dex or CD40
      ligand was IgM (>97%), with the remainder comprising IgG. Surprisingly, picogram
      per-milliliter amounts of neisserial LPS were also found to be highly synergistic
      with anti-Ig-dex for induction of IgM secretion by LPS-responsive C3H/HeN, but
      not C3H/HeJ, B cells. Thus, these data suggest that porins, as well as LPS, may
      provide critical second signals for T-cell-independent induction of
      polysaccharide-specific Ig in response to neisserial and other gram-negative
      porin-expressing bacterial pathogens, without a requirement for the participation
      of non-B cell types. These data may also help to explain the potent
      immunopotentiating effects of porins for polysaccharide-specific, as well as
      protein-specific, humoral responses in vivo.

PMID- 9234777
TI  - Interaction of Escherichia coli heat-stable enterotoxin B with cultured human
      intestinal epithelial cells.
AB  - Binding of Escherichia coli heat-stable enterotoxin B (STb) to the human
      intestinal epithelial cell lines T84 and HT29 and to polarized T84 cells was
      studied to define the initial interaction of this peptide toxin with target
      cells. Equilibrium and competitive binding isotherms showed that 125I-STb bound
      specifically to T84 and HT29 cells; however, the toxin-epithelial cell
      interactions could be characterized by low-affinity binding (< or = 10(5) M(-1))
      to a high number of binding sites (> or = 10(6) per cell). STb binding to T84 and
      HT29 cells as a function of 125I-STb concentration did not approach saturation at
      levels well above the effective biological concentration of STb for fluid
      secretion. Treatment of the 125I-STb-bound T84 and HT29 cells with an acidic
      saline solution to remove surface-bound toxin revealed that only approximately
      55% +/- 10% of 125I-STb could be removed by this treatment at 4 degrees C,
      suggesting that approximately half of the bound STb was stably associated with
      the plasma membrane and/or internalized into the cytoplasm. Similar results were
      obtained when binding and internalization experiments were conducted at 22 and 37
      degrees C. Immunofluorescence studies demonstrated that the strongest signal for
      STb appeared in the plasma membrane even after acid treatment. Toxin-treated
      cells also displayed diffuse cytoplasmic staining, indicating that once cell
      bound, STb did not appear to preferentially associate with membrane vesicles or
      cellular organelles. Binding and subsequent internalization of 125I-STb were not
      affected by treatment of the cells with trypsin, endoglycosidase F/peptide N
      glycosidase F, Vibrio cholerae neuraminidase, tunicamycin, or 5 mM sodium
      chlorate, which blocks sulfation of surface proteoglycans. In addition, the
      internalization process was not altered by preincubation of the cells with the
      cytoskeleton inhibitors cytochalasin D and colchicine or cellular perturbants
      (i.e., 0.45 M sucrose and 5 mM sodium azide), indicating that cell surface
      proteins or carbohydrates did not function as STb receptors. The binding of 125I
      STb to polarized T84 cells was also examined, and the total and nonspecific
      binding isotherms were found to overlap, indicating that the apical surface of
      polarized T84 cells did not contain a specific receptor for STb. In comparison to
      undifferentiated cells, twice the amount of bound STb (approximately 80% +/- 10%)
      was removable from polarized T84 cells after treatment with acidic solution. The
      percentage of surface-bound STb to polarized T84 cells did not vary significantly
      with the transepithelial electrical resistance of the cells or when STb was
      applied basolaterally. Together, our results indicate that STb binds with
      relatively low affinity to the plasma membrane of cultured intestinal epithelial
      cells and polarized T84 cells, probably to membrane lipids, and becomes stably
      associated with the lipid bilayer. The fact that a significant portion of the
      bound STb becomes free in the cytoplasm, even at a low temperature, suggests that
      the bound toxin may directly traverse the membrane bilayer.

PMID- 9234778
TI  - Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a
      gastric cancer cell line, MKN45.
AB  - Accumulating evidence suggests an important role of interleukin-8 (IL-8) in
      Helicobacter pylori infection-associated chronic atrophic gastritis and peptic
      ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45,
      produced a massive amount of IL-8 upon coculture with live H. pylori but not with
      killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by
      a permeable membrane, indicating that IL-8 production requires a direct contact
      between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor
      herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein
      kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with
      live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori
      induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA
      expression in MKN45 cells and an increase in luciferase activity in cells which
      were transfected with a luciferase expression vector linked with a 5'-flanking
      region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8
      production occurred at the transcriptional level. This region contain three cis
      elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp),
      NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of
      the NF-kappaB binding site abrogated completely the induction of luciferase
      activity, whereas that of the AP-1 site partially reduced the induction. However,
      mutation of the NF-IL6 binding site resulted in no decrease in the induction of
      luciferase activity. Moreover, specific NF-kappaB complexes were detected in the
      nuclear proteins extracted from MKN45 cells which were infected with H. pylori.
      Collectively, these results suggest that H. pylori induced the activation of NF
      kappaB as well as AP-1, leading to IL-8 gene transcription.

PMID- 9234779
TI  - Successful therapy of chronic, nonhealing murine cutaneous leishmaniasis with
      sodium stibogluconate and gamma interferon depends on continued interleukin-12
      production.
AB  - Treatment of nonhealing forms of human leishmaniasis with antimonial drugs in
      combination with gamma interferon (IFN-gamma) may promote healing more
      effectively than conventional drug therapy. Although the natures of immune
      responses in patients prior to treatment are often unclear, it is generally
      assumed that such therapy also promotes a switch from a Th2-type response to a
      dominant Th1-type response. We have examined the efficacy of IFN-gamma therapy,
      in combination with drug therapy, to promote healing and a Th2-to-Th1 switch in
      highly susceptible BALB/c mice infected with Leishmania major. Short-term
      treatment with the antileishmanial drug sodium stibogluconate failed to
      significantly alter the course of disease or the immune response when it was
      given during the third and fourth weeks of infection. IFN-gamma therapy,
      administered over the same time period, also failed to induce cure or a Th1
      dominant response. In contrast, mice treated with a combination of drug and IFN
      gamma therapy resolved their infections and developed Th1-type responses.
      However, administration of an antibody to interleukin 12 (IL-12) reversed the
      therapeutic effects of therapy with drug plus IFN-gamma, suggesting that IFN
      gamma promotes cure through an IL-12-dependent mechanism. Analysis of mRNA levels
      within parasitized lesions suggests that drug treatment plus IFN-gamma treatment,
      in addition to reducing parasite numbers, results in reduced levels of IL-4, IL
      10, and transforming growth factor beta transcripts but increased levels of
      transcripts of the p40 chain of IL-12 and inducible nitric oxide synthase, which
      catalyzes the production of nitric oxide. Together, these results suggest that
      such immunotherapy may promote the development of a protective Th1-type response
      in susceptible mice by a mechanism which involves both suppression of regulatory
      cytokines and enhancement of IL-12 and nitric oxide production.

PMID- 9234780
TI  - Cystalysin, a 46-kilodalton cysteine desulfhydrase from Treponema denticola, with
      hemolytic and hemoxidative activities.
AB  - A 46-kDa hemolytic protein, referred to as cystalysin, from Treponema denticola
      ATCC 35404 was overexpressed in Escherichia coli LC-67. Both the native and
      recombinant 46-kDa proteins were purified to homogeneity. Both proteins expressed
      identical biological and functional characteristics. In addition to its
      biological function of lysing erythrocytes and hemoxidizing the hemoglobin to
      methemoglobin, cystalysin was also capable of removing the sulfhydryl and amino
      groups from selected S-containing compounds (e.g., cysteine) producing H2S, NH3,
      and pyruvate. This cysteine desulfhydrase resulted in the following Michaelis
      Menten kinetics: Km = 3.6 mM and k(cat) = 12 s(-1). Cystathionine and S
      aminoethyl-L-cysteine were also substrates for the protein. Gas chromatography
      mass spectrometry and high-performance liquid chromatography analysis of the end
      products revealed NH3, pyruvate, homocysteine (from cystathionine), and
      cysteamine (from S-aminoethyl-L-cysteine). The enzyme was active over a broad pH
      range, with highest activity at pH 7.8 to 8.0. The enzymatic activity was
      increased by beta-mercaptoethanol. It was not inhibited by the proteinase
      inhibitor TLCK (N alpha-p-tosyl-L-lysine chloromethyl ketone), pronase, or
      proteinase K, suggesting that the functional site was physically protected or
      located in a small fragment of the polypeptide. We hypothesize that cystalysin is
      a pyridoxal-5-phosphate-containing enzyme, with activity of an alphaC-N and betaC
      S lyase (cystathionase) type. Since large amounts of H2S have been reported in
      deep periodontal pockets, cystalysin may also function in vivo as an important
      virulence molecule.

PMID- 9234782
TI  - Effects of Porphyromonas gingivalis and Escherichia coli lipopolysaccharides on
      mononuclear phagocytes.
AB  - The mononuclear phagocyte plays an important role in the regulation of microbe
      induced inflammation, in part through its ability to secrete mediators,
      particularly cytokines, in response to microorganisms and their products. To
      evaluate the effects of the microbial flora associated with chronic adult
      periodontitis on cytokine induction, lipopolysaccharide (LPS) from the
      periodontopathogen Porphyromonas gingivalis was used to stimulate naive and
      phorbol ester-primed U937 monocytic cells, as well as elutriated human peripheral
      blood monocytes. We assessed the effect of this LPS, in comparison to that of LPS
      from Escherichia coli, on cell proliferation, cytokine induction, and surface
      expression of the LPS receptor CD14. P. gingivalis LPS stimulated proliferation
      of U937 cells at concentrations of greater than 1 ng/ml, while E. coli LPS
      inhibited proliferation. Phorbol myristic acid (PMA)-treated U937 cells and
      elutriated monocytes responded to E. coli LPS activation by producing tumor
      necrosis factor alpha (TNF-alpha) mRNA and protein; however, P. gingivalis LPS
      induced greater numbers of TNF-alpha mRNA-positive cells and higher (P < 0.05)
      levels of protein than did E. coli LPS. Both cell types expressed interleukin-1
      beta (IL-1beta) mRNA and protein in response to either LPS treatment. Compared
      with E. coli LPS, P. gingivalis LPS induced significantly (P < 0.05) higher
      numbers of IL-1 mRNA-positive U937 cells and elutriated monocytes, as well as
      production of significantly more (P < 0.05) IL-1 protein by the monocytes. The
      PMA-treated U937 cells and the monocytes produced high levels of IL-1 receptor
      antagonist mRNA and protein which were only marginally affected by the LPS
      preparations. While E. coli LPS induced expression of CD 14 on the surface of PMA
      primed U937 cells and monocytes, P. gingivalis LPS exhibited a significantly (P <
      0.05) greater ability to enhance receptor levels. Our results indicate that P.
      gingivalis LPS can activate the mononuclear phagocyte for proliferation, cytokine
      production, and CD14 expression, providing evidence for the potential of this
      bacterial component to act as a critical regulatory factor in the chronic
      inflammatory response associated with periodontitis.

PMID- 9234783
TI  - Coexistence of CD14-dependent and independent pathways for stimulation of human
      monocytes by gram-positive bacteria.
AB  - The cell wall is a key inflammatory agent of gram-positive bacteria. Possible
      receptors mediating cell wall-induced inflammation include CD14 and platelet
      activating factor (PAF) receptor. To delineate the conditions under which these
      various receptors might be used, human monocytic THP-1 cells and heparinized
      whole human blood were stimulated with lipopolysaccharide (LPS), intact
      Streptococcus pneumoniae bacteria, or purified pneumococcal cell wall. THP-1
      culture supernatant or cell-free plasma was analyzed for the presence of tumor
      necrosis factor, interleukin-1beta (IL-1beta), and IL-6. For the cultured
      monocytes, anti-CD14 inhibited induction of the inflammatory cytokines by the
      cell wall and LPS but not by intact pneumococcal bacteria. Despite the difference
      in CD-14 usage, the intracellular pathways induced by the three agents
      demonstrated similarities, as revealed in the presence of specific signal
      transduction inhibitors such as cholera toxin, pertussis toxin, and genistein.
      Cytokine production in whole human blood indicated that anti-CD14 failed to block
      responses to cell wall and intact pneumococci, whereas while LPS-induced
      responses were inhibited. PAF receptor antagonist had no effect under any
      conditions in both assays. These results indicate that although cell walls bind
      to both CD14 and PAF receptor, only CD14 appears to engender a cytokine response
      under restricted conditions. Furthermore, host cell responses to intact
      pneumococci are consistently independent of CD14 and PAF receptor.

PMID- 9234781
TI  - Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin
      12, gamma interferon, and interleukin-10 mRNA production in murine macrophages.
AB  - Monophosphoryl lipid A (MPL) is a nontoxic derivative of the lipid A region of
      lipopolysaccharide (LPS) that is being developed as both an adjuvant and
      prophylactic drug for septic shock. We compared the ability of LPS and MPL to
      induce interleukin-10 (IL-10), IL-12 p35, IL-12 p40, gamma interferon (IFN
      gamma), glucocorticoid receptor (GR), IL-1 receptor antagonist (IL-1ra), and
      inducible nitric oxide synthase mRNA expression in murine peritoneal macrophages.
      These genes were chosen for their ability to positively or negatively regulate
      the host immune response and thus for their potential involvement in MPL-induced
      adjuvanticity or in its ability to protect against sepsis. LPS was a more potent
      inducer of IL-12 p35, IL-12 p40, and IFN-gamma mRNA, as well as of IL-12 protein,
      than MPL. In contrast, MPL induced higher levels of IL-10 mRNA than did LPS from
      1 to 1,000 ng/ml. In general, MPL was not a more potent inducer of negative
      regulatory genes, since MPL and LPS induced similar levels of GR and IL-1ra mRNA.
      Addition of anti-IL-10 antibody to cultures increased the induction of MPL
      induced IL-12 p35, IL-12 p40, and IFN-gamma mRNA, suggesting that the enhanced
      production of IL-10 by MPL-stimulated macrophages contributes to decreased
      production of mRNA for IL-12 (p35 and p40) and IFN-gamma. Conversely, the
      addition of exogenous IL-10 to LPS-treated macrophages reduced the mRNA
      expression of these cytokine genes. These studies suggest that enhanced
      production of IL-10 by MPL-stimulated macrophages may contribute to the reduced
      toxicity of MPL through its negative action on induction of cytokines shown to
      enhance endotoxicity.

PMID- 9234784
TI  - Infection with Salmonella typhimurium modulates the immune response to
      Schistosoma mansoni glutathione-S-transferase.
AB  - Immune response polarization is controlled by several factors, including
      cytokines, antigen-presenting cells, antigen dose, and others. We have previously
      shown that adjuvants and live vectors play a critical role in polarization. Thus,
      immunization with the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28
      GST) in aluminum hydroxide induced a type 2 cytokine profile and the production
      of immunoglobulin G1 (IgG1)- and IgE-specific antibodies. In contrast, mice
      infected with recombinant Salmonella typhimurium expressing Sm28-GST developed a
      type 1 cytokine profile and produced IgG2a-specific antibodies against Sm28-GST
      and Salmonella antigens. In this study, to determine if S. typhimurium not
      expressing Sm28-GST would still influence the type of the response against this
      antigen, we compared the profiles of the immune responses generated against Sm28
      GST administered in alum in mice infected and not infected with S. typhimurium.
      Infected mice generated both IgG1 and IgG2a antibodies against Sm28-GST, while
      noninfected mice produced only IgG1 anti-Sm28-GST antibodies. Moreover,
      interleukin-4 (IL-4) mRNA expression in infected mice was near background levels,
      while gamma interferon (IFN-gamma) mRNA expression in coinfected mice was
      significantly higher than in mice immunized with Sm28-GST in alum only. However,
      after antigen-specific stimulation in vitro with Sm28-GST, levels of IL-4 and IFN
      gamma cytokine production were similar in the two groups of mice. These results
      suggest that (i) the immune milieu produced during an infection may modify the
      response against an irrelevant antigen and (ii) isotype switching may be
      influenced by the cytokine environment of a bystander immune response, even
      though the specific antigen-driven cytokine production is not modified. Thus, the
      isotypic profile is not always an absolute reflection of the cytokines produced
      by antigen-specific Th cells.

PMID- 9234785
TI  - The baboon as a nonhuman primate model for assessing the effects of maternal
      immunization with Haemophilus influenzae type b polysaccharide vaccines.
AB  - These studies were performed to assess the utility of the baboon as a nonhuman
      primate model to evaluate vaccines for use in humans. Specifically, we examined
      the antibody response of baboons immunized during the third trimester of
      pregnancy with Haemophilus influenzae type b (Hib) polyribosylribitol phosphate
      (PRP) conjugate and unconjugated polysaccharide vaccines. Some of the vaccinated
      mothers failed to respond to a single immunization with unconjugated Hib PRP.
      Specific Hib PRP immunoglobulin G (IgG) but not IgM antibodies cross the baboon
      placenta and are detected in the offspring. Higher-titer baboon anti-Hib PRP did
      not express two previously defined cross-reactive human anti-Hib PRP idiotypes
      and was biased towards lambda light-chain expression. Spectrotype analysis
      indicated that baboon anti-Hib PRP was restricted in heterogeneity and
      oligoclonal.

PMID- 9234786
TI  - Prognostic value of anti-Plasmodium falciparum-specific immunoglobulin G3,
      cytokines, and their soluble receptors in West African patients with severe
      malaria.
AB  - Forty-one African patients suffering from clinically defined severe malaria were
      studied in the intensive medical care unit of the main hospital in Dakar,
      Senegal, West Africa. All of these individuals lived in Greater Dakar, an area of
      low and seasonal Plasmodium falciparum endemicity. Twenty-seven patients (mean
      age +/- 1 standard deviation, 19.2 +/- 12.7 years) survived this life-threatening
      episode, but 14 (30.8 +/- 16.2 years old) died despite initiation of adequate
      treatment. On the day of admission (day 0) and 3 days later, one to two blood
      samples (i.e., approximately 10 to 15 ml) were obtained from each subject, and
      different biological parameters were evaluated in the two groups. Plasma samples
      were tested for their content in tumor necrosis factor alpha (TNF-alpha), soluble
      receptors I and II for TNF-alpha (TNF-alpha sRI and TNF-alpha sRII), interleukin
      6 (IL-6), IL-6 sR, IL-10, and IL-2 sR. The concentrations of all these cytokines
      and/or their receptors was significantly elevated in patient plasma samples on
      day 0, and it rapidly decreased in the group of individuals who survived. By
      comparison, the mean concentration of the same parameters decreased slowly in the
      group of patients who died (except for IL-10, which dramatically fell in all
      patient plasma samples soon after initiation of antimalarial treatment). The TNF
      alpha sRI level remained significantly elevated among the patients who died, and
      the highest levels of soluble TNF-alpha sRI receptor were found among the older
      patients. Parasite-specific immunoglobulin M (IgM), total IgG, IgG1, IgG2, IgG3,
      and IgG4 were evaluated by enzyme-linked immunosorbent assay using a crude
      extract of a local P. falciparum isolate as antigen and human class- and subclass
      specific monoclonal antibodies. Parasite-specific IgM, total IgG, and IgG1 were
      detectable in the plasma samples of most of these African patients, whereas IgG2
      and IgG4 mean values were low. The mean level of parasite-specific IgG3 was
      different (P = 0.024) at day 0, i.e., before initiation of intensive medical
      care, between the group of the 27 surviving subjects and the group of 14 patients
      dying of severe malaria. As a consequence, most of the African patients who died
      had only trace amounts or almost no detectable level of parasite-specific IgG3 at
      the time of admission. In contrast, the presence of even limited IgG3 activity at
      day 0 was found to be associated with a significantly increased probability of
      recovering from severe malaria. Therefore, in our study, both an elevated level
      of TNF-alpha sRI and absence of IgG3 activity were of bleak prognostic
      significance, whereas a favorable outcome was usually observed when parasite
      specific IgG3 activity was detectable. This finding was strongly suggestive of a
      prime role for these parasite-specific immunoglobulins in the capacity to help
      recovery from severe malaria.

PMID- 9234787
TI  - Activation of host cell protein kinase C by enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) consists of a group of diarrhea
      producing E. coli strains, common in developing countries, which do not produce
      classical toxins and are not truly invasive. EPEC strains adhere to mammalian
      cells in an intimate fashion, trigger a localized increase in intracellular
      calcium levels, and elevate inositol phosphate production. We hypothesized that
      these mediators could activate host cell protein kinase C (PKC) and tested this
      idea in vitro with two cultured human cell lines, HeLa cells and T84 cells. Using
      a recently described subculturing protocol to "induce" or accelerate EPEC
      adherence, we infected the cells with EPEC at a multiplicity of infection of
      approximately 100:1 for 30 to 60 min. Under these conditions, EPEC E2348
      increased membrane-bound PKC activity 1.5- to 2.3-fold in HeLa cells and T84
      cells, respectively. The increase in membrane-bound PKC activity was accompanied
      by a decrease in cytosolic PKC activity in EPEC-infected HeLa cells. Nonadherent
      laboratory E. coli strains such as HB101 and H.S. failed to trigger any
      consistent change in PKC production, similar to the nonadherent mutant strains
      derived from E2348, JPN15 (plasmid cured) and CVD206 (eaeA). In addition,
      immunoblots performed on extracts of T84 cells with a monoclonal antibody against
      PKC-alpha showed an increased PKC content in membranes of EPEC-infected cells.
      Finally, EPEC-infected T84 cells showed a 60% increase in responsiveness to the
      E. coli heat-stable toxin. We conclude that mediators produced in response to
      EPEC adherence activate PKC in intestinal and nonintestinal cells.

PMID- 9234788
TI  - Complement fragment C5a and inflammatory cytokines in neutrophil recruitment
      during intramammary infection with Escherichia coli.
AB  - Generation of inflammatory mediators and leukocyte recruitment to infection at an
      epithelial surface were studied during Escherichia coli-induced mastitis. One
      uninfected gland of each of eight midlactation cows was challenged with only 30
      CFU of E. coli McDonald strain 487, a serum-resistant isolate from a cow with
      mastitis. Bacteria grew logarithmically during the first 10 to 12 h after
      challenge, reaching concentrations of more than 10(5) CFU/ml with no detectable
      host response during this time. An intense inflammatory reaction began
      approximately 12 h after the challenge and was characterized by a breakdown in
      the blood-milk permeability barrier followed by pyrexia and a pronounced
      leukocytic influx. Coincident with the onset of mammary inflammation was the
      appearance of neutrophil chemotactic activity in the milk from infected glands.
      Factors able to upregulate CD18 expression on peripheral blood neutrophils also
      appeared in milk at this time. The lack of appearance of chemotactic and CD18
      upregulating activities until 12 h after challenge indicated that delays in
      neutrophil recruitment resulted from an initial lack of bacterial recognition and
      inflammatory mediator production. Production of complement fragment C5a, tumor
      necrosis factor, and interleukin-1 (IL-1) occurred earlier than production of IL
      6 or IL-8. The early and intense production of C5a indicates that this
      chemoattractant may be more important than IL-8 during the initial recruitment
      and activation of neutrophils to a developing E. coli infection.

PMID- 9234789
TI  - Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro
      is correlated with enhanced virulence in experimental endocarditis due to
      Staphylococcus aureus.
AB  - Thrombin-induced platelet microbicidal protein (tPMP) is secreted by rabbit
      platelets following thrombin stimulation, and it kills common endovascular
      pathogens in vitro, including Staphylococcus aureus. Therefore, pathogens which
      exhibit tPMP resistance in vitro possess a potential survival advantage in vivo
      at sites of endovascular damage. We generated an isogenic S. aureus strain pair,
      differing in tPMP susceptibility, by transposon (Tn551) mutagenesis of a tPMP
      susceptible (tPMPs) parental strain (ISP479) to derive a stably tPMP-resistant
      (tPMPr) strain, ISP479R. ISP479 and ISP479R were equivalent in vitro in the
      following phenotypes: biotyping, antiobiograms, platelet adherence and
      aggregation, growth kinetics, cell wall-associated protein A expression, and
      fibrinogen binding. Genotypic comparisons of chromosomal DNA of strains ISP479
      and ISP479R following restriction endonuclease digestion revealed
      indistinguishable pulsed-field gel electrophoretic patterns. The genotype
      exhibited by strain ISP479R was linked to the tPMP-resistant phenotype, as it was
      transducible into the initially tPMP-susceptible parental strain, ISP479.
      Southern hybridization verified the presence of a single copy of Tn551 in the
      same chromosomal restriction site of both ISP479R and tPMPr transductants of
      ISP479. The correlation of in vitro tPMP susceptibility phenotypes with the
      ability to induce experimental endocarditis (a prototypical endovascular
      infection) was evaluated. Despite equivalent rates of endocarditis induction,
      animals infected with strain ISP479R achieved significantly higher vegetation
      bacterial densities over a 7-day post-challenge period than did animals infected
      with strain ISP479. These data suggest that tPMPr microbial strains have a
      selective advantage in experimental staphylococcal endocarditis. Furthermore, the
      major impact of tPMP resistance upon endocarditis pathogenesis appears to involve
      a postvalvular adherence event(s), most probably by facilitating bacterial
      proliferation within vegetations.

PMID- 9234790
TI  - Potential role of autoantibodies in the regulation of cytokine responses during
      bacterial infections.
AB  - An immunoregulatory mechanism involving release of neutralizing autoantibodies
      (Aabs) to self cytokines during bacterial infections is presented herein.
      Intraperitoneal inoculation of Haemophilus influenzae type b into Sprague-Dawley
      rats resulted in a self-limiting meningitis. High levels of cells expressing mRNA
      for gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) were
      detected 12 to 48 h postinoculation (p.i.) in splenocytes, and large numbers of
      IFN-gamma-secreting cells were present in the spleen on day 3 p.i. These levels
      were undetectable at days 9 and 14 p.i. Increased titers of Aabs of
      immunoglobulin G (IgG) isotypes to both cytokines were observed, with a peak at
      day 7 p.i. and with very low levels at day 30. Upon reinoculation with H.
      influenzae type b at day 30, regeneration of Aabs was recorded 7 days later
      (i.e., at day 37). To elucidate their regulatory importance, Aabs dose
      dependently inhibited IFN-gamma production by splenocytes, IFN-gamma-induced
      major histocompatibility complex expression by peritoneal macrophages, and TNF
      alpha-induced thymocyte proliferation. To control the specificity of these Aabs,
      Fab fragments of purified serum Igs from day p.i. exhibited binding and
      neutralizing effects. Furthermore, preincubation of the sera with a cytokine
      inhibited the binding and neutralization effects of that particular cytokine, but
      not those of any other cytokine. Aab-producing B cells were cloned, and their
      supernatants had similar effects. Our data suggest a role for autoimmunity in
      cytokine regulation and suggest that a maintained balance of this mechanism may
      protect from sequelae.

PMID- 9234791
TI  - Ecto-ADP-ribosyltransferase activity of Pseudomonas aeruginosa exoenzyme S.
AB  - Pseudomonas aeruginosa produces two ADP-ribosyltransferases, exotoxin A and
      exoenzyme S (ExoS). Although the physiological target protein remains to be
      defined, ExoS has been shown to ADP-ribosylate several eukaryotic proteins in
      vitro, including vimentin and members of the family of low-molecular-weight GTP
      binding proteins. Recently, ExoS ADP-ribosyltransferase activity has been
      detected in the pleural fluid of rabbits infected with P. aeruginosa. This
      observation prompted an examination of the potential for ExoS to function as an
      ecto-ADP-ribosyltransferase. We have observed that ExoS preferentially ADP
      ribosylated two extracellular serum proteins with molecular masses of 150 and 27
      kDa. The ADP-ribosylation of these serum proteins by ExoS was stimulated by, but
      not dependent upon, exogenous FAS (for factor activating exoenzyme S), which
      indicated that serum contained endogenous FAS activity. Biochemical analysis
      showed that the 150-kDa ADP-ribosylated protein was immunoglobulin of the
      immunoglobulin G (IgG) and IgA classes. Subtyping showed that ExoS preferentially
      ADP-ribosylated human IgG3 and that ADP-ribosylation occurred within its Fc
      region. The 27-kDa protein ADP-ribosylated by ExoS was determined to be
      apolipoprotein A1. These data demonstrate ecto-ADP-ribosyltransferase activity by
      ExoS. This may extend the potential physiological consequences of ExoS during
      infection by P. aeruginosa beyond the implicated type III secretion-mediated
      intracellular delivery of ExoS into sensitive eukaryotic cells.

PMID- 9234792
TI  - The endotoxin of Helicobacter pylori is a modulator of host-dependent gastritis.
AB  - Atrophic gastritis caused by Helicobacter pylori is the precursor lesion in the
      development of intestinal-type gastric adenocarcinoma. In animal models, atrophic
      gastritis induced by Helicobacter felis has been shown to be host dependent,
      developing in some mouse strains and not in others. The lipopolysaccharide (LPS)
      of H. pylori has been suggested to play a role in the induction of gastritis. The
      goal of this study was to compare the inflammation induced by long-term infection
      of the C3H/He and the C3H/HeJ strains of mice with H. felis. C3H/HeJ mice are
      unresponsive to LPS. Six months after infection, severe atrophic gastritis had
      developed in the body mucosae of all infected C3H/He mice, with replacement of
      parietal and chief cells. Atrophy was associated with a loss of the H. felis from
      the antral mucosa. In contrast, no atrophy was seen in the infected C3H/HeJ non
      LPS responder animals, and heavy colonization of the antrum remained. There were
      no significant differences between both the quantitative and qualitative serum
      immunoglobulin G (IgG) and salivary IgA levels in both strains of mice. The main
      difference between the two strains of long-term-infected mice was a lack of
      macrophage infiltration in the lamina propria. Immunization induced good
      protective immunity to challenge with viable H. felis. Helicobacter-induced, host
      dependent gastritis is likely to be cell mediated. The C3H/He and C3H/HeJ mouse
      model provides an excellent opportunity to investigate the cellular basis of
      atrophic gastritis.

PMID- 9234793
TI  - Pathogenesis of tuberculosis in mice exposed to low and high doses of an
      environmental mycobacterial saprophyte before infection.
AB  - Mycobacteria are ubiquitous in the environment, but they are not part of the
      normal human microbial flora. It has been suggested that variable contact with
      mycobacteria can influence susceptibility to mycobacterial pathogens and the
      efficacy of subsequent Mycobacterium bovis BCG vaccination. To test this, mice
      were immunized with high or low doses of an environmental saprophyte, M. vaccae,
      that is intensely immunogenic as an autoclaved preparation. Two months later,
      they received an intratracheal challenge with M. tuberculosis H37Rv. Recipients
      of a low Th1-inducing dose (10(7) organisms) were partially protected and
      maintained a high ratio of interleukin 2 (IL-2)-positive to IL-4-positive cells
      in the perivascular, peribronchial, and granulomatous areas of the lung, whereas
      in unimmunized controls the IL-4-positive cells increased markedly between days
      21 and 28. In contrast, recipients of the high dose (10(9) organisms), which
      primes Th2 as well as Th1 cytokine production, died more rapidly than unimmunized
      controls and showed massive pneumonia from day 7. The ratio of IL-2-positive to
      IL-4-positive cells in all compartments of the lung rapidly fell to 1 by day 14
      for these animals. These events correlated with cytokine mRNA profiles and with
      increases in the local toxicity of tumor necrosis factor alpha (TNF-alpha),
      demonstrable only when a major Th2 component was present. These data indicate
      that cross-reactive epitopes present in an environmental saprophyte can evoke
      either protective responses or responses that increase susceptibility to M.
      tuberculosis. The latter are associated with the presence of a Th2 component and
      increased sensitivity to TNF-alpha.

PMID- 9234794
TI  - Human papillomavirus type 16 virus-like particles expressed in attenuated
      Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in
      mice.
AB  - Attenuated strains of Salmonella are attractive live vaccine candidates for
      eliciting mucosal as well as systemic immune responses. The ability to induce
      immune responses in the reproductive tract may be critical for the effectiveness
      of a prophylactic vaccine against genital human papillomaviruses (HPV), which are
      important etiologic agents in the development of cervical cancer. To examine the
      potential of a live Salmonella-based vaccine to prevent genital HPV infection,
      the L1 major capsid protein from HPV type 16 (HPV16) was constitutively expressed
      in the PhoPc strain of Salmonella typhimurium. As demonstrated by electron
      microscopy, the L1 protein expressed in these bacteria assembled into virus-like
      particles (VLPs) that resemble authentic papillomavirus virions. This is the
      first demonstration that papillomavirus VLPs can self-assemble in prokaryotes.
      BALB/c mice were immunized with the HPV16 L1 recombinant PhoPc strain by the oral
      and nasal routes. Despite a low stability of the L1-expressing plasmid in vivo, a
      double nasal immunization was effective in inducing L1-specific serum antibodies
      that recognized mainly native, but not disassembled, VLPs. These antibodies
      effectively neutralized HPV16 pseudotyped virions in an in vitro infectivity
      assay. Conformationally dependent anti-VLP immunoglobulin A (IgA) and IgG were
      also detected in oral and vaginal secretions, indicating that potentially
      protective antibody responses were elicited at mucosal sites. Recombinant
      attenuated Salmonella expressing HPV capsids may represent a promising vaccine
      candidate against genital HPV infection.

PMID- 9234795
TI  - Sensitization of human umbilical vein endothelial cells to Shiga toxin:
      involvement of protein kinase C and NF-kappaB.
AB  - Infection of humans with Shiga toxin-producing Escherichia coli O157:H7 and
      Shigella dysenteriae 1 is strongly associated with vascular endothelial cell
      damage and the development of hemolytic-uremic syndrome. The cytotoxic effect of
      Shiga toxins on vascular endothelial cells in vitro is enhanced by prior exposure
      to bacterial lipopolysaccharide (LPS) or either of the host cytokines tumor
      necrosis factor alpha (TNF) and interleukin-1beta (IL-1). The purpose of this
      study was to examine individual signal transduction components involved in the
      sensitization of human umbilical vein endothelial cells (HUVEC) to Shiga toxin 1.
      The results demonstrate that class I and II protein kinase C (PKC) isozymes are
      required for sensitization of HUVEC to Shiga toxin by phorbol myristate acetate
      (PMA) or LPS but not by TNF or IL-1. Thus, the specific competitive inhibitor of
      class I/II PKC, 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG), prevented only the
      action of PMA and LPS on HUVEC. Additional data obtained with ATP binding site
      inhibitors which affect all PKCs (i.e., classes I, II, and III) suggest that TNF
      may utilize class III PKC isozymes in the Shiga toxin sensitization of HUVEC.
      Transcriptional activator NF-kappaB did not appear to be involved in the
      sensitization of HUVEC to Shiga toxin by LPS, TNF, IL-1, or PMA. Thus, the
      specific serine protease inhibitor L-1-tosylamido-2-phenylethyl chloromethyl
      ketone (TPCK) did not inhibit the sensitization of HUVEC to Shiga toxin by LPS,
      TNF, IL-1, or PMA despite its ability to inhibit NF-kappaB activation and the
      induction of the NF-kappaB-dependent tissue factor gene by these agents. Finally,
      all-trans retinoic acid partially inhibited the sensitization of HUVEC to Shiga
      toxin, by unknown mechanisms which also appeared to be independent of NF-kappaB
      activation. These results indicate that PKC plays a role in the sensitization of
      HUVEC to Shiga toxin in response to some, but not all, sensitizing agents. In
      contrast, NF-kappaB activation appears not to be involved in the sensitization of
      HUVEC to Shiga toxin by LPS, TNF, IL-1, or PMA.

PMID- 9234796
TI  - Colonization of congenitally immunodeficient mice with probiotic bacteria.
AB  - We assessed the capacity of four probiotic bacteria (Lactobacillus acidophilus,
      Lactobacillus reuteri, Lactobacillus casei GG, and Bifidobacterium animalis) to
      colonize, infect, stimulate immune responses in, and affect the growth and
      survival of congenitally immunodeficient gnotobiotic beige-athymic (bg/bg-nu/nu)
      and beige-euthymic (bg/bg-nu/+) mice. The bacteria colonized and persisted, in
      pure culture, in the alimentary tracts of both mouse strains for the entire study
      period (12 weeks). Although all adult and neonatal beige-euthymic mice survived
      probiotic colonization, some infant mortality occurred in beige-athymic pups born
      to mothers colonized with pure cultures of L. reuteri or L. casei GG. The
      probiotic bacteria manifested different capacities to adhere to epithelial
      surfaces, disseminate to internal organs, affect the body weight of adult mice
      and the growth of neonatal mice, and stimulate immune responses. Although the
      probiotic species were innocuous for adults, these results suggest that caution
      and further studies to assess the safety of probiotic bacteria for
      immunodeficient hosts, especially neonates, are required.

PMID- 9234797
TI  - Immunologic and genetic analyses of VmpA of a neurotropic strain of Borrelia
      turicatae.
AB  - In mice infected with serotype A but not serotype B of the relapsing fever
      spirochete Borrelia turicatae, early invasion of the brain occurs. Serotypes A
      and B are further distinguished by the abundant surface protein they produce:
      VmpA and VmpB, respectively. Western blotting with monoclonal antibodies, one
      dimensional peptide mapping, and partial amino acid sequencing demonstrated
      regions of the VmpA protein that differed from VmpB. Oligonucleotide primers
      based on the partial amino acid sequences of unique regions were used to amplify
      a portion of the VmpA gene (vmpA) by PCR, and the product was used as a probe in
      Southern blot and Northern blot analyses. These experiments showed that (i)
      expression of the vmpA sequence was determined at the level of transcription and
      (ii) the vmpA sequence was in two locations in serotype A and one location in
      serotype B. The vmpA gene at the expression-linked locus of serotype A was cloned
      and sequenced. An open reading frame would encode a polypeptide of 214 amino
      acids. The polypeptide expressed by Escherichia coli was bound by VmA-specific
      but not VmpB-specific antibody. Primer extension analysis identified a consensus
      sigma70-type promoter for vmpA at the expression locus. Phylogenetic analysis
      revealed that VmpA is homologous to small Vmp (Vsp) proteins of B. hermsii and to
      OspC proteins of B. burgdorferi. These findings indicate that a function of the
      Vsp-OspC family of proteins of Borrelia spp. may be differential localization in
      organs, including the brain, during infection.

PMID- 9234798
TI  - Immunization with an acellular vaccine consisting of the outer membrane complex
      of Chlamydia trachomatis induces protection against a genital challenge.
AB  - The ability to induce protection against a genital challenge was studied in
      BALB/c female mice with three Chlamydia trachomatis mouse pneumonitis (MoPn)
      major outer membrane protein (MOMP) preparations as well as an acellular vaccine
      consisting of the chlamydial outer membrane complex (COMC). The MOMP preparations
      were extracted with three different types of detergents, sodium dodecyl sulfate
      (SDS), n-octyl-beta-D-glucopyranoside (OGP), and Zwittergent 3-14 (Z3-14). A
      positive immunization control consisted of mice inoculated intranasally with
      10(4) C. trachomatis MoPn inclusion-forming units (IFU). Mice inoculated with
      ovalbumin served as a negative control. Furthermore, a sham-immunized,
      nonchallenged group was included as a fertility control. Two weeks after the last
      immunization, the mice were challenged in the left ovarian bursa with 10(5) C.
      trachomatis MoPn IFU. Vaginal swabs were collected for culture, vaginal and serum
      samples were assayed for chlamydial-specific antibodies, and splenocytes were
      collected to determine the lymphoproliferative response. At 42 days after the
      challenge, the mice were mated with proven male breeder mice. Animals that were
      considered to be pregnant (as determined by weight) were killed, and the embryos
      were counted. A significant humoral and cell-mediated immune response was
      observed in all the groups of mice inoculated with chlamydial antigens.
      Antibodies to variable domain (VD)1 of the MOMP were detected in serum samples
      from all the immunized groups. However, antibodies to VD3 and VD4 were detected
      only in the groups immunized with the Z3-14-MOMP and the COMC. Mice immunized
      with COMC developed significant immunoglobulin A chlamydia-specific antibodies in
      the vagina, while mice immunized with the detergent-extracted MOMPs had low
      antibody titers. Following the intrabursal challenge, a significant decrease in
      the intensity and duration of vaginal shedding was noted in the mice immunized
      with COMC and a moderate decrease was noted in the group immunized with OGP-MOMP.
      No protection against the infection was noted in the groups of animals immunized
      with SDS- and Z3-14-MOMP. Furthermore, of the mice immunized with the COMC
      preparation, only 25% (4 of 20) shed C. trachomatis, as determined by vaginal
      culture, while 83% (40 of 48) of the control mice inoculated with ovalbumin were
      culture positive (P < 0.05). In addition, after mating, the mice inoculated with
      COMC were found to have fertility rates comparable to those of the control sham
      immunized, nonchallenged animals (70% [14 of 20] versus 81% [17 of 21],
      respectively [P > 0.05]), and there were no significant differences between the
      average number of embryos per mouse in the two groups (5.1 versus 5.9,
      respectively [P > 0.05]). In contrast, mice immunized with the purified MOMP
      preparations were not protected against infertility. In summary, a preparation of
      the COMC protected mice against infection and infertility, supporting the
      feasibility of the development of an acellular vaccine against C. trachomatis
      infections.

PMID- 9234799
TI  - A role for PACE4 in the proteolytic activation of anthrax toxin protective
      antigen.
AB  - Several bacterial protein toxins require activation by eukaryotic proteases.
      Previous studies have shown that anthrax toxin protective antigen (PA),
      Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) are cleaved by furin C
      terminal to the sequences RKKR, RQPR, and RVRR, respectively. Because furin
      deficient cells retain some sensitivity to PA and DT, it is evident that other
      cellular proteases can activate these toxins. Whereas furin has been shown to
      require arginine residues at positions -1 and -4 for substrate recognition,
      another protease with an activity which could substitute for furin in toxin
      activation, the furin-related protease PACE4, requires basic residues in the -1, 
      2, and -4 positions of the substrate sequence. To examine the relative roles of
      furin and PACE4 in toxin activation, we used furin-deficient CHO cells (FD11
      cells) transfected with either the furin (FD11/furin cells) or PACE4 (FD11/PACE4
      cells) gene. Mutant PA proteins containing the cleavage sequence RAAR or KR were
      cytotoxic toward cells expressing only PACE4. In vitro cleavage data demonstrated
      that PACE4 can recognize RAAR and, to a much lesser extent, KR and RR. When
      extracts from PACE4-transfected cells were used as a source of proteases, PACE4
      had minimal activity, indicating that it had been partially inactivated or did
      not remain associated with the cell membranes. Cleavage of iodinated PA
      containing the sequence RKKR or RAAR was detected on the surface of all cell
      types tested, but cleavage of a dibasic sequence was detected only
      intracellularly and only in cells that expressed furin or PACE4. The data provide
      evidence that PACE4 is present at the exterior of cells, that it plays a role in
      the proteolytic activation of anthrax toxin PA, and that PACE4 can activate
      substrates at the sequence RAAR or KR.

PMID- 9234800
TI  - Identification of a Coccidioides immitis antigen 2 domain that expresses B-cell
      reactive epitopes.
AB  - Antigen 2 (Ag2), a major immunoreactive component of Coccidioides immitis
      mycelium- and spherule-phase cell walls, was recently cloned in our laboratory
      and was shown to elicit T-cell responses in Coccidioides-immune mice. In this
      investigation, we evaluated recombinant Ag2 (rAg2) and PCR-generated Ag2
      truncations for expression of B-cell-reactive epitopes in enzyme-linked
      immunosorbent and immunoblot assays with sera from patients with active
      coccidioidomycosis, a hyperimmune goat anti-Ag2 serum, and a murine anti-Ag2
      monoclonal antibody that recognizes a conformational epitope. The results
      established that rAg2 expresses both linear and conformational B-cell-reactive
      epitopes which are localized to a domain comprised of amino acids 19 through 96
      (designated A19-96). Truncations designed to identify epitopes within the A19-96
      domain yielded fragments that either were nonreactive (A62-194, A19-61, and A49
      79) or showed reduced reactivity (A19-79). Hence, A19-96 was the shortest domain
      expressing epitopes recognized by the panel of antibodies. The prevalence of
      antibodies to the A19-96 domain was evaluated in enzyme-linked immunosorbent
      assays of sera from 28 coccidioidomycosis patients. Antibody reactivity was
      detected in 79% of the patients' sera, and the level of antibody reactivity was
      directly correlated with disease severity. Whereas patients with pulmonary
      disease showed a mean response (A405) of 0.16 +/- 0.04, patients with
      disseminated coccidioidomycosis showed a mean response of 0.69 +/- 0.17 (P <
      0.05). No reactivity was detected with sera from histoplasmosis or blastomycosis
      patients. The production of a recombinant peptide that expresses C. immitis
      specific Ag2 epitopes provides a useful reagent for examining the role of anti
      Ag2 antibodies in coccidioidomycosis.

PMID- 9234801
TI  - Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine
      vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the
      Asd-balanced lethal vector system.
AB  - Attenuated Salmonella typhi organisms which express genes encoding protective
      antigens of other pathogens have been developed for use as experimental oral
      vaccines. A delta asd S. typhi strain attenuated by deletions in cya, crp, and
      cdt which contains hepatitis B core (HBc) and pre-S genes encoded on an Asd+ pBR
      based plasmid vector was constructed. Healthy adult volunteers ingested a single
      dose of 5 x 10(5) to 5 x 10(8) CFU of strain chi4073 (delta cya delta crp delta
      cdt S. typhi Ty2), 6 x 10(7) or 1 x 10(9) CFU of strain chi4632(pYA3149), a
      further derivative of chi4073 deleted in asd and containing the Asd+ vector
      without the HBc-pre-S fusion, or 3 x 10(7) or 7 x 10(8) CFU of strain
      X4632(pYA3167), a derivative containing the vector with the HBc-pre-S fusion.
      Chi4073 was generally well tolerated by 22 volunteers. No volunteer had fever or
      positive blood cultures; 4 of 22 volunteers shed vaccine organisms in the stool
      in the first 48 h only. Two of 18 volunteers who received one of the plasmid
      containing derivatives of chi4073 developed low-grade fevers on day 10 or 12
      after ingestion. One of these volunteers had positive blood cultures on days 7
      and 8. Seven of these 18 volunteers had vaccine organisms detected in their
      stools in the first 48 h only. Most volunteers developed S. typhi-specific serum
      responses and developed S. typhi-specific antibody-secreting cells. However, no
      volunteer developed serum antibody to hepatitis pre-S or pre-S-specific antibody
      secreting cells. Although the parent strain chi4073 was well tolerated, induced
      immunoglobulin G seroconversion to S. typhi lipopolysaccharide in 80 to 100% of
      vaccinees and stimulated specific IgA-secreting lymphocytes in 80 to 100% of
      vaccinees given a single oral dose of 2 x 10(7) and 5 x 10(8) CFU, chi4073
      derivatives containing the Asd+ vector with and without sequences encoding the
      HBc-pre-S fusion caused occasional febrile reactions at high doses and did not
      stimulate detectable immune responses to hepatitis B antigens.

PMID- 9234802
TI  - Borrelia burgdorferi-pulsed dendritic cells induce a protective immune response
      against tick-transmitted spirochetes.
AB  - Borrelia burgdorferi-pulsed dendritic cells and epidermal cells were able to
      initiate the production of anti-outer surface protein A (OspA) antibody in vitro
      with normal T and B cells from either BALB/c or C3H/HeJ mice. Inhibition of anti
      B. burgdorferi antibody production was observed after 3 days, but not after 2
      days, of exposure of the antigen-presenting cells to tumor necrosis factor alpha
      +/- granulocyte-macrophage colony-stimulating factor. Furthermore, splenic
      dendritic cells pulsed in vitro with live B. burgdorferi spirochetes and then
      adoptively transferred into naive syngeneic mice mediated a protective immune
      response against tick-transmitted spirochetes. This protection appeared not to be
      due to killing of spirochetes in the feeding ticks, since ticks fed to repletion
      on B. burgdorferi-pulsed dendritic cell-sensitized mice still harbored live
      spirochetes. Western blot analysis of the sera collected from dendritic cell
      sensitized mice demonstrated that the mice responded to a limited set of B.
      burgdorferi antigens, including OspA, -B, and -C compared to control groups that
      either had received unpulsed dendritic cells or were not treated. Finally, mice
      in the early stage of B. burgdorferi infection were able to develop anti-OspA
      antibody following injection with B. burgdorferi-pulsed dendritic cells. Our
      results demonstrate for the first time that adoptive transfer of B. burgdorferi
      pulsed dendritic cells induces a protective immune response against tick
      transmitted B. burgdorferi and stimulates the production of antibodies specific
      for a limited set of B. burgdorferi antigens in vivo.

PMID- 9234803
TI  - Experimental infection of native human ureteral tissue with Neisseria
      gonorrhoeae: adhesion, invasion, intracellular fate, exocytosis, and passage
      through a stratified epithelium.
AB  - The exact mechanisms by which Neisseria gonorrhoeae invades the mucosal lining to
      cause local and disseminated infections are still not fully understood. The
      ability of gonococci to infect the human ureter and the mechanism of gonococcal
      infection in a stratified epithelium were investigated by using distal ureters
      excised from healthy adult kidney donors. In morphological terms, this tissue
      closely resembles parts of the urethral proximal epithelium, a site of natural
      gonococcal infection. Using piliated and nonpiliated variants of N. gonorrhoeae
      MS11, we demonstrated the importance of pili in the attachment of gonococci to
      native epithelial cells as well as their association with epithelial damage. By
      electron microscopy we elucidated the different mechanisms of colonization and
      invasion of a stratified epithelium, including adherence to surface cells,
      invasion and eventual release from infected cells, disintegration of
      intercellular connections followed by paracellular tissue infiltration, invasion
      of deeper cells, and initiation of cellular destruction and exfoliation resulting
      in thinning of the mucosa.

PMID- 9234804
TI  - Protective role of antimannan and anti-aspartyl proteinase antibodies in an
      experimental model of Candida albicans vaginitis in rats.
AB  - The role of antibodies (Abs) in the resistance to vaginal infection by Candida
      albicans was investigated by using a rat vaginitis model. Animals receiving
      antimannoprotein (anti-MP) and anti-aspartyl proteinase (Sap) Ab-containing
      vaginal fluids from rats clearing a primary C. albicans infection showed a highly
      significant level of protection against vaginitis compared to animals given Ab
      free vaginal fluid from noninfected rats. Preabsorption of the Ab-containing
      fluids with either one or both proteins MP and Sap sequentially reduced or
      abolished, respectively, the level of protection. A degree of protection against
      vaginitis was also conferred by postinfectious administration of anti-Sap and
      anti-MP monoclonal antibodies (provided the latter were directed against mannan
      rather than protein epitopes of MP) and by intravaginal immunization with a
      highly purified, polysaccharide-free Sap preparation. Postinfectious
      administration of pepstatin A, a potent Sap inhibitor, greatly accelerated the
      clearance of C. albicans from rat vagina. No anti-MP or anti-Sap Abs were
      elicited during a C. albicans vaginal infection of congenitally athymic nude
      rats. Although they were as able as their euthymic counterparts to clear the
      primary infection, these animals did not show increased resistance to a
      rechallenge, demonstrating that induction of anticandidal protection in normal
      rats was a thymus-dependent Ab response. Overall, our data strengthen the concept
      that Abs against some defined Candida antigens are relevant in the mechanism of
      acquired anticandidal protection in vaginitis. The T-cell dependence of this
      protection may also provide a link between cell-mediated and humoral immunity in
      vaginal infection.

PMID- 9234805
TI  - Expression profile and subcellular location of the plasmid-encoded virulence
      (Spv) proteins in wild-type Salmonella dublin.
AB  - The plasmid-encoded virulence genes (spvABCD) in nontyphoid Salmonella strains
      mediate lethal infections in a variety of animals. Previous studies have shown
      that these genes are transcriptionally regulated by stationary-phase growth. We
      studied the expression profile and the subcellular locations of the SpvABCD
      proteins in wild-type S. dublin by using polyclonal antibodies against SpvA,
      SpvB, SpvC, and SpvD. The cellular levels of the individual proteins were
      determined during growth by quantitative immunoblotting. As expected, SpvA, SpvB,
      SpvC, and SpvD were not detectable before the late logarithmic growth phase and
      appeared in the sequence SpvA, SpvB, SpvC, and SpvD. In contrast to the
      transcriptional regulation, however, SpvA and SpvB reached their maximal
      expression shortly after induction and declined during further growth whereas
      SpvC and SpvD expression remained high throughout the stationary phase,
      indicating that the Spv proteins are individually regulated at a
      posttranscriptional level. To localize SpvABCD within the bacteria, the cells
      were fractionated into the periplasmic, cytoplasmic, inner membrane, and outer
      membrane components. The cell fractions and the culture supernatant were analyzed
      by immunoblotting. SpvA was present in the outer membrane, SpvB was present in
      the cytoplasm and the inner membrane, and SpvC was present in the cytoplasm. SpvD
      was secreted into the supernatant; however, a substantial portion of this protein
      was also detected in the cytoplasm and membranes. The molecular weights of SpvD
      in the supernatant and in the cytoplasm appeared to be equal, suggesting that
      SpvD is not cleaved upon secretion.

PMID- 9234806
TI  - Invasin-dependent and invasin-independent pathways for translocation of Yersinia
      pseudotuberculosis across the Peyer's patch intestinal epithelium.
AB  - Yersinia pseudotuberculosis initiates systemic disease after translocation across
      the intestinal epithelium. Three Y. pseudotuberculosis factors, previously
      identified by their ability to promote association with cultured cells, were
      evaluated for their relative roles in translocation. To this end, mutants
      defective for invasin, YadA, or pH 6 antigen were tested for movement from the
      intestinal lumen into the subepithelium. Within 45 min after introduction of
      bacteria into the lumen, wild-type bacteria were found in the Peyer's patch.
      Mutants expressing defective invasin derivatives were unable to promote efficient
      translocation into the Peyer's patch and instead colonized on the luminal surface
      of the intestinal epithelium. In particular, a translocation defect was observed
      in a Y. pseudotuberculosis strain that expressed an uptake-defective invasin
      protein retaining considerable receptor binding activity. To attempt to reduce
      binding to luminal mucus, Y. pseudotuberculosis yadA and inv yadA strains were
      analyzed. Both strains had reduced mucus binding, with the inv yadA mutant
      revealing an alternate uptake pathway that was invasin independent. A mutant
      defective in the production of the pH 6 antigen adhesin also showed reduced
      binding to luminal mucus, with specific localization of bacteria in M cells.
      These results indicate that Y. pseudotuberculosis adhesive factors control the
      site of bacterial interaction within the intestinal environment and that loss of
      one factor causes drastic changes in the preferred site of localization of the
      bacterium in this locale.

PMID- 9234807
TI  - Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a
      neutropenic murine model of trichosporonosis.
AB  - We produced disseminated trichosporonosis in a neutropenic murine model with
      Trichosporon asahii, which was identified by DNA relatedness analysis. We then
      assessed the efficacy of granulocyte colony-stimulating factor (G-CSF) (30 to 100
      microg/kg of body weight per day) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) (0.8 to 2 microg/kg x day). The administration of G-CSF either
      before or after infection improved the survival rate from less than 25% up to
      100% (P < 0.05). The effects of G-CSF on organ clearance and histological
      examinations were most remarkable in the lungs. The levels of tumor necrosis
      factor alpha (TNF-alpha) in bronchoalveolar lavage fluid (BALF) of neutropenic
      and G-CSF-pretreated mice were 60 +/- 6 ng/ml and 18 +/- 6 pg/ml, respectively,
      at 24 h after infection. Immunohistologically, alveolar macrophages proved to be
      the main source of TNF-alpha in BALF. GM-CSF increased neutrophil counts less
      significantly than did G-CSF and increased the lethality (P < 0.05) with a high
      level of TNF-alpha in BALF. Expecting to inhibit TNF-alpha, we administered anti
      TNF-alpha intraperitoneally at the dose completely inhibiting TNF-alpha in plasma
      (2 x 10(4) U), but the TNF-alpha level in BALF and the lethality increased.
      Though the number of neutrophils at the early stage of infection appeared to be
      the most critical, the results suggest that other host defense mechanisms, such
      as TNF-alpha overproduction in the lungs, have an important role in the prognosis
      of trichosporonosis.

PMID- 9234808
TI  - Development of two monoclonal antibodies against Plasmodium falciparum sporozoite
      surface protein 2 and mapping of B-cell epitopes.
AB  - The Plasmodium yoelii sporozoite surface protein 2 (PySSP2) is the target of
      protective cellular immunity. Cytotoxic T cells specific for the Plasmodium
      falciparum analog PfSSP2, also known as thrombospondin-related anonymous protein
      (TRAP), are induced in human volunteers immunized with irradiated sporozoites.
      PfSSP2 is an important candidate antigen for a multicomponent malaria vaccine. We
      generated and characterized three monoclonal antibodies (MAbs) specific for
      PfSSP2/TRAP. The MAbs PfSSP2.1 (immunoglobulin G1 [IgG1]), PfSSP2.2 (IgG2a), and
      PfSSP2.3 (IgM) were species specific and identified three distinct B-cell
      epitopes containing sequences DRYI, CHPSDGKC, and TRPHGR, respectively. PfSSP2.1
      partially inhibited P. falciparum liver-stage parasite development in human
      hepatocyte cultures (42 and 86% in two experiments at 100 microg/ml). Mice
      immunized with vaccinia virus expressing full-length PfSSP2 protein produced
      antibodies to (DRYIPYSP)3, and humans living in malaria-endemic areas (Indonesia
      and Kenya), who have lifelong exposure and partial clinical immunity to malaria,
      had antibodies to both (DRYIPYSP)3 and (CHPSDGKCN)2. Mice immunized with multiple
      antigen peptides MAP4 (DRYIPYSP)3P2P30 and MAP4 (CHPSDGKCN)3P2P30 in TiterMax
      developed antibodies to sporozoites that partially inhibited sporozoite invasion
      of human hepatoma cells (39 to 71% at a serum dilution of 1:50 in three different
      experiments). The modest inhibitory activities of the MAbs and the polyclonal
      antibodies to PfSSP2/TRAP epitopes do not suggest that a single-component vaccine
      designed to induce antibodies against PfSSP2/TRAP will be protective.
      Nonetheless, the MAbs directed against PfSSP2, and the peptides recognized by
      these MAbs, will be essential reagents in the development of PfSSP2/TRAP as a
      component of a multivalent P. falciparum human malaria vaccine.

PMID- 9234809
TI  - Local expression of tumor necrosis factor alpha in an experimental model of acute
      osteomyelitis in rats.
AB  - The inflammatory response associated with Staphylococcus aureus osteomyelitis
      results in extensive bone damage characterized by apparent increases in bone
      resorption and formation. These results suggest an increased local release of
      agents capable of modulating bone remodelling. Tumor necrosis factor alpha (TNF
      alpha) is a proinflammatory cytokine proposed to play an important role both in
      normal bone remodelling and in bone diseases; however, its potential role in
      osteomyelitis is unclear. This study evaluated changes in bone TNF levels during
      infection, using a rat model of acute osteomyelitis due to S. aureus. Following
      direct tibial infection, bacterial counts in bone were persistently high
      (approximately 6 log10 CFU/g of bone over 63 days) and bone weights increased.
      TNF activity was undetectable in uninfected bone (<0.01 ng/g of bone) but
      dramatically higher in infected bone (up to 5.2 +/- 3.5 ng/g of bone). Although
      TNF-alpha mRNA was weakly detected in uninfected bone, osteomyelitis was
      associated with up to 37-fold increases in expression of both the 1.6- and 2.4-kb
      transcripts. Both TNF activity and mRNA transcript levels remained elevated
      throughout the course of infection. TNF-alpha mRNA detected by in situ
      hybridization was present in osteoblasts as well as in populations of marrow
      cells and/or inflammatory infiltrate cells. Histopathology of infected bone
      indicated extensive bone resorption and adjacent areas of formation that were
      associated with cells expressing TNF-alpha mRNA. These data suggest that the
      elevated TNF levels induced by experimental infection may be directly related to
      changes in the histology of bone during osteomyelitis.

PMID- 9234810
TI  - Synthesis, stability, and subcellular distribution of major histocompatibility
      complex class II molecules in Langerhans cells infected with Leishmania major.
AB  - Protozoan parasites of the genus Leishmania exist as obligatory intracellular
      amastigotes and invade macrophages and Langerhans cells, the dendritic cells of
      the skin. Langerhans cells are much more efficient in presenting Leishmania major
      antigen to T cells than macrophages are and have the unique ability to retain
      parasite antigen in immunogenic form for prolonged periods. To analyze the
      mechanisms that are responsible for this potency, we defined the synthesis,
      turnover, conformation, and localization of major histocompatibility complex
      (MHC) class II molecules in Langerhans cells. Hence, Langerhans cells were pulse
      labeled; immunoprecipitation of MHC class II molecules and gel electrophoresis
      followed. In addition, the subcellular distribution of MHC class II molecules in
      L. major-infected Langerhans cells was analyzed by confocal microscopy. The
      results show that (i) newly synthesized MHC class II molecules are required for
      L. major antigen presentation by Langerhans cells, (ii) MHC class II-peptide
      complexes in Langerhans cells are long-lived, (iii) phagocytosis of L. major
      modulates MHC class II biosynthesis by reducing its downregulation during
      Langerhans cell differentiation, and (iv) newly synthesized MHC class II
      molecules are associated with the parasitophorous vacuole of infected Langerhans
      cells. These findings support the conclusion that the traits of MHC class II
      expression correspond to the highly specialized functions of Langerhans cells in
      the immunoregulation of cutaneous leishmaniasis.

PMID- 9234811
TI  - Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in
      Escherichia coli-induced transuroepithelial neutrophil migration.
AB  - Escherichia coli stimulates neutrophil migration across human uroepithelial cell
      layers. This study investigated the role of the neutrophil chemokine interleukin
      8 (IL-8) in this process. E. coli and IL-1alpha stimulated urinary tract
      epithelial layers to secrete IL-8 and induced transepithelial neutrophil
      migration. Anti-IL-8 antibody reduced neutrophil migration across epithelial cell
      layers, indicating a central role for this chemokine in the migration process.
      Furthermore, addition of recombinant IL-8 to unstimulated cell layers was
      sufficient to induce migration. The IL-8 dependence of neutrophil migration was
      maintained after removal of soluble IL-8 by washing of the cell layers. Flow
      cytometry analysis with fluorescein isothiocyanate-labelled IL-8 confirmed IL-8's
      ability to bind to the epithelial cell surface. Indirect immunofluorescence with
      confocal laser scanning microscopy showed that IL-8 associated with the
      epithelial cell layers. Prior incubation of neutrophils with antibodies to IL-8
      receptor A (IL-8RA) reduced neutrophil migration. Anti-IL-8 RB antibody had no
      effect on neutrophil migration. These results demonstrate that IL-8 plays a key
      role in E. coli- or IL-1alpha-induced transuroepithelial migration and suggest
      that epithelial cell-produced IL-8 interacts with IL-8RA on the neutrophil
      surface.

PMID- 9234812
TI  - Mice lacking the gamma interferon receptor have an impaired granulomatous
      reaction to Schistosoma mansoni infection.
AB  - The egg-induced granulomatous reaction in Schistosoma mansoni-infected
      individuals develops within the portal system of the liver and is the major
      pathological finding in schistosomiasis. We have infected mice lacking the gamma
      interferon (IFN-gamma) receptor with S. mansoni larvae and studied the
      development of hepatic granulomas in these mutant mice in comparison to that in
      control wild-type mice. In the absence of IFN-gamma activity, a dramatic
      reduction in the size and architecture of the granuloma was observed. Granulomas
      from mutant mice were smaller than those from the control group and showed a
      significant reduction in the number of infiltrating inflammatory cells. Moreover,
      they appear to prematurely progress to the chronic phase of the reaction at a
      time when the control group still has acute inflammation. Our data suggests a
      pivotal role for IFN-gamma in the early events of the granulomatous reaction in
      vivo.

PMID- 9234813
TI  - Role of vacuolating cytotoxin in gastritis due to Helicobacter pylori in
      gnotobiotic piglets.
AB  - To investigate the role of the Helicobacter pylori cytotoxin in the pathogenesis
      of gastritis, gnotobiotic piglets were colonized with either toxigenic H. pylori
      or a nontoxigenic isogenic mutant. Only piglets given the toxigenic strain
      developed toxin-neutralizing antibodies (indicating that toxin is expressed in
      vivo), but there was no difference in bacterial colonization, epithelial
      vacuolation, or gastritis between the two groups of piglets.

PMID- 9234814
TI  - Characterization of a recombinant fragment that contains a carbohydrate
      recognition domain of the filamentous hemagglutinin.
AB  - The filamentous hemagglutinin (FHA) of Bordetella pertussis plays an important
      role in establishing infection by attaching the bacteria to the ciliated
      respiratory epithelial cells. Expression of DNA encoding residues 1141 to 1279 of
      FHA in Escherichia coli yields a protein of 18,000 Da that exhibits some of the
      carbohydrate recognition properties of FHA (S. M. Prasad, Y. Yin, E. Rodzinski,
      E. I. Tuomanen, and H. R. Masure, Infect. Immun. 61:2780-2785, 1993). We have
      constructed an E. coli strain that expresses this protein, designated fragment A,
      in a soluble form at markedly elevated levels. Fragment A could be purified with
      high purity and yields and was immunogenic in mice. Both fragment A and anti
      fragment A sera inhibited the binding of B. pertussis to asialo-GM2 and to rabbit
      ciliated cells. These observations demonstrate that this fragment of FHA contains
      a cellular binding domain capable of eliciting functional antibodies.

PMID- 9234815
TI  - Phase variation affects long-term survival of Bordetella bronchiseptica in
      professional phagocytes.
AB  - Several Bordetella bronchiseptica isolates were investigated for intracellular
      survival in macrophages. A significant number of viable bacteria of all strains
      could be recovered even after 96 h postinfection. In all cases bvg mutants of the
      B. bronchiseptica strains showed a significant survival advantage over the
      respective wild-type strains. The bacteria were already located in phagolysosomes
      early after uptake. Neither opsonization of the bacteria nor activation of the
      macrophages with gamma interferon or lipopolysaccharide prior to infection
      affected uptake and survival of the bacteria.

PMID- 9234816
TI  - Adherence of Vibrio cholerae to cultured differentiated human intestinal cells:
      an in vitro colonization model.
AB  - Choleragenic vibrios adhered to and multiplied on monolayers of the highly
      differentiated mucin-secreting cell line HT29-18N2. Their adherence followed
      first-order kinetics, was dependent on the concentration of vibrios, and was
      partially inhibited by lipopolysaccharide. Comparison of genetically modified
      vibrios showed that flagella, an active toxR gene, and the virulence cassette
      were not essential for initial binding. Inactivation of the
      hemagglutinin/protease increased binding. This highly differentiated human
      intestinal cell line provides a versatile new approach for studying major events
      occurring during intestinal colonization: adherence, multiplication, and
      detachment.

PMID- 9234817
TI  - A novel cryohemagglutinin associated with adherence of enteroaggregative
      Escherichia coli.
AB  - Strain O42 (serotype O44:H18) of enteroaggregative Escherichia coli (EAggEC) has
      been shown to be pathogenic in volunteer experiments. This strain exhibited
      plasmid (pO42)-encoded D-mannose-resistant hemagglutinating activity (MRHA) that
      was detected only at low temperatures (e.g., 0 degrees C) and only with human
      erythrocytes. The production of this cryogenic MRHA (cryo-MRHA) was observed when
      the bacteria were grown in liquid media and was strictly regulated by bacterial
      growth temperatures. Transposon-insertion mutagenesis revealed that this MRHA is
      associated with (i) bacterial clump formation in liquid cultures, (ii) bacterial
      adherence to HEp-2 cells as well as (Formalin-fixed) human colonic mucosa, and
      (iii) production of a 16-kDa outer membrane protein. The PCR designed on the
      basis of the determined cryo-MRHA-associated DNA sequence sharply distinguished
      strain O42 from eight other EAggEC strains whose MRHAs were detected at both cold
      and room temperatures to the same (or similar) extent. Strain O42 possessed a
      surface layer that may enhance the pO42-mediated adherence. The data suggest that
      a plasmid-encoded cryo-MRHA is a candidate for a major adhesin of EAggEC strain
      O42.

PMID- 9234818
TI  - Clostridium perfringens enterotoxin lacks superantigenic activity but induces an
      interleukin-6 response from human peripheral blood mononuclear cells.
AB  - We investigated the potential superantigenic properties of Clostridium
      perfringens enterotoxin (CPE) on human peripheral blood mononuclear cells (PBMC).
      In contrast to the findings of a previous report (P. Bowness, P. A. H. Moss, H.
      Tranter, J. I. Bell, and A. J. McMichael, J. Exp. Med. 176:893-896, 1992), two
      different, biologically active preparations of CPE had no mitogenic effects on
      PBMC. Furthermore, PBMC incubated with various concentrations of CPE did not
      elicit interleukin-1, interleukin-2, gamma interferon, or tumor necrosis factor
      alpha or beta, which are cytokines commonly associated with superantigenic
      stimulation. However, CPE did cause a dose-related release of interleukin-6 from
      PBMC cultures.

PMID- 9234819
TI  - Site-specific mutagenesis of Clostridium perfringens alpha-toxin: replacement of
      Asp-56, Asp-130, or Glu-152 causes loss of enzymatic and hemolytic activities.
AB  - The current study has investigated the role of D-56, D-130, and E-152 in zinc ion
      binding properties, as well as the hemolytic, phospholipase C (PLC), and
      sphingomyelinase (SMase) activities of Clostridium perfringens alpha-toxin, based
      upon crystallography studies of the Bacillus cereus PLC, which had suggested
      these residues might be important for these functional activities. The
      replacement of D-56 in alpha-toxin resulted in complete loss of hemolytic, PLC,
      and SMase activities. The variant toxins at D-130 showed an approximately 100
      fold reduction of biological activities compared to that of the wild-type toxin.
      The substitution of glutamine or glycine for E-152 caused complete loss of these
      activities, but substitution of aspartic acid for E-152 reduced but did not
      completely inhibit these activities. The variant toxins at D-56 and D-130, as
      well as the wild-type toxin, possessed approximately 2 mol of zinc atoms per mol
      of the protein, but E152G and E152Q contained approximately 1 mol of zinc metal
      per mol of the protein. On the other hand, the zinc content in E152D was
      calculated as about 1.4 mol in the toxin molecule. The replacement of D-56, D
      130, or E-152 had no effect on binding to sheep erythrocytes and uptake of free
      zinc ion from the solution. The variant toxins at D-130 showed partial antigenic
      identity with the wild-type toxin on a double gel diffusion test. These
      observations suggest that D-56 in alpha-toxin is required for catalytic activity
      of alpha-toxin, D-130 is essential for maintenance of structure, and the carboxyl
      group of E-152 tightly ligands one zinc ion, which is essential for catalytic
      activity of the toxin.

PMID- 9234820
TI  - Effect of thermal injury on the adherence of Candida albicans to murine splenic
      tissue.
AB  - In a mouse model of thermal injury, an increase in burn size produced a decrease
      in the ratio of Candida albicans cells adherent to the marginal zone to those
      adherent to the white pulp of the spleen, an increase in the number of Candida
      cells in the circulation and in the kidneys, and an increase in mortality.

PMID- 9234821
TI  - Purification and identification of Haemophilus ducreyi cytotoxin by use of a
      neutralizing monoclonal antibody.
AB  - Haemophilus ducreyi produces a cytotoxin responsible for the killing of cultured
      human epithelial cells. Cytotoxin-neutralizing antibodies were detected in the
      majority of sera from patients with culture-proven chancroid, and a significantly
      higher level of such antibodies in patients than in blood donors was noted both
      in areas where the disease is endemic and those where it is not. We produced
      neutralizing monoclonal antibodies (MAbs) in mice with a crude osmotic
      preparation of the cytotoxin. These antibodies, with high capacity to neutralize
      cytotoxicity, were used for purification and identification of the cytotoxin.
      Purification was performed by a two-step procedure which included Sephacryl S-200
      filtration followed by immunoaffinity chromatography. The purification resulted
      in poor cytotoxin protein recovery and contamination with MAbs from the affinity
      column. The results of the gel filtration experiments and immunoblotting indicate
      that the active cytotoxin consists of a single, small protein with an approximate
      molecular mass of 20 kDa. Cytotoxins from different strains seem to have the same
      or similar epitopes. The cytotoxin protein was not detected in preparations from
      nontoxic strains. The N-terminal amino acid sequence of the 20-kDa band was E-S-N
      P-D-P-T-T-Y-P-D-V-E-L-S-P-P-P. This sequence does not resemble that of any
      currently known bacterial protein.

PMID- 9234822
TI  - The effects of initial drug choice and comorbidity on antihypertensive therapy
      compliance: results from a population-based study in the elderly.
AB  - Approximately half of all elderly patients have elevated blood pressure, and
      proper treatment of this disorder leads to decreased cardiovascular morbidity in
      patients 65 and older. This study examined the effect of initial drug choice and
      comorbidity on medication compliance. We conducted a retrospective follow-up of
      8643 outpatients aged 65 to 99 with newly prescribed antihypertensive therapy
      (AHT) from 1982 to 1988 in the New Jersey Medicaid and Medicare programs.
      Compliance was measured in terms of the number of days in which AHT was available
      to the patient during the 12 months following the initiation of therapy. Odds
      ratios (OR) and 95% confidence intervals (CI) for the outcome of good compliance
      (> or =80%) were calculated. In a logistic regression model, good compliance (>
      or =80%) was significantly associated with use of newer agents such as
      angiotensin converting enzyme inhibitors (OR 1.9, 95% CI 1.6 to 2.2) and calcium
      channel blockers (OR 1.7, 95% CI 1.5 to 2.1) as compared to thiazides, the
      presence of comorbid cardiac disease (OR 1.2, 95% CI 1.1 to 1.2), and multiple
      physician visits (OR 2.2, 95% CI 1.8 to 2.5). Good compliance was inversely
      associated with use of multiple pharmacies (OR 0.4, 95% CI 0.4 to 0.5) and number
      of medications prescribed overall (OR 0.8, 95% CI 0.7 to 0.9). Drug choice,
      comorbidity, and health services utilization were significantly associated with
      AHT compliance and represent important considerations in the management of high
      blood pressure. Noncompliance may be an important cause of treatment failure in
      elderly hypertensives.

PMID- 9234823
TI  - The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study:
      rationale, design, and methods. The LIFE Study Group.
AB  - The treatment of hypertension mainly with diuretics and beta blockers reduces
      cardiovascular mortality and morbidity, largely due to a decreased incidence of
      stroke, whereas the beneficial effects of antihypertensive therapy on the
      occurrence of coronary events have been less than expected from epidemiological
      studies. Furthermore, treated hypertensive patients still have a higher
      cardiovascular complication rate, compared with matched normotensives. This is
      particularly evident in patients with left ventricular hypertrophy (LVH), a major
      independent risk indicator for cardiovascular disease. In addition to elevating
      blood pressure, angiotensin II (A-II) exerts an important influence on cardiac
      structure and function, stimulating cell proliferation and growth. Thus, to
      further reduce morbidity and mortality when treating hypertensive patients, it
      may be important to effectively block the effects of A-II. This can be achieved
      directly at the A-II receptor level by losartan, the first of a new class of
      antihypertensive agents. It therefore seems pertinent to investigate whether
      selective A-II receptor blockade with losartan not only lowers blood pressure but
      also reduces LVH more effectively than current therapy, and thus improves
      prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in
      Hypertension study is a double-blind, prospective, parallel group study designed
      to compare the effects of losartan with those of the beta-blocker atenolol on the
      reduction of cardiovascular morbidity and mortality in approximately 8,300
      hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg
      or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically
      documented LVH. The study, which will continue for at least 4 years and until
      1,040 patients experience one primary endpoint, has been designed with a
      statistical power that will detect a difference of at least 15% between groups in
      the incidence of combined cardiovascular morbidity and mortality. It is also the
      first prospective study with adequate power to link reversal of LVH to reduction
      in major cardiovascular events. The rationale of the study, which will involve
      more than 800 clinical centers in Scandinavia, the United Kingdom, and the United
      States, is discussed, and the major features of its design and general
      organization are described. On April 30, 1997, when inclusion was stopped, 9,218
      patients had been randomized.

PMID- 9234824
TI  - Plasma insulin-like growth factor 1 distribution and its relation to blood
      pressure in adolescents: the Bogalusa Heart Study.
AB  - The distribution of circulating insulin-like growth factor-1 (IGF-1) and its
      relationship to blood pressure was examined in a community study of 1073 biracial
      (black-white) adolescents aged 11 to 18 years. Girls of both races displayed
      higher levels of plasma IGF-1 than did their male counterparts (P < .01),
      independent of age and sexual maturation. In boys, IGF-1 was correlated
      positively with height (r = 0.37 P < .001), weight (r = 0.26, P < .001), Tanner
      stage (r = 0.31, P < .001), and age (r = 0.11, P < .05). Girls, on the other
      hand, showed an inverse association with age (r = -0.38, P < .001) and Tanner
      stage (r = -0.10, P < .05). Plasma IGF-1 was correlated positively with systolic
      blood pressure in boys of both races (r = 0.21 to 0.25, P < .01) and with
      diastolic blood pressure in white boys (r = 0.18, P < .05), but not in girls of
      either race. Boys with elevated levels of IGF-1 (>80th percentile) showed
      significantly higher blood pressure levels, especially during early to middle
      stages of puberty. Multivariate analysis revealed that IGF-1 was associated with
      systolic and diastolic blood pressure, independent of age, race, sexual
      maturation, height, weight, and insulin in boys. These results suggest that
      plasma IGF-1 may contribute to the regulation of blood pressure only in males
      during puberty.

PMID- 9234825
TI  - Chronic salt overload increases blood pressure and improves glucose metabolism
      without changing insulin sensitivity.
AB  - The effect of sodium chloride salt restriction and overload on insulin
      sensitivity is still an open question. Some authors have shown that NaCl salt
      restriction increases insulin resistance, whereas others have reported the
      opposite. In the present study, the objective was to get some more insight on
      this issue by studying the influence of dietary salt content on glucose uptake in
      isolated adipocytes. Male Wistar rats were fed from weaning either low (0.15%) or
      high (7.94%) salt diets. On the 12th week of age, weight and tail-cuff blood
      pressure were measured, followed 10 days later by an intravenous glucose
      tolerance test with concomitant insulin determinations. One week later, the rats
      were killed by decapitation and epididymal adipocytes were obtained for glucose
      metabolism evaluation. No weight differences were observed between both groups of
      animals. Blood pressure was significantly higher (P < .001) on salt overloaded
      rats (146 +/- 11 mm Hg) than on salt restricted ones (115 +/- 5 mm Hg). Dietary
      salt content did not influence the area under the curve of plasma glucose. Area
      under the curve of insulin levels was lower (P = .023) on the high than on the
      low salt diet. A higher (P < .001) glucose uptake in the absence and in the
      presence of insulin was observed in adipocytes from rats on the high salt diet.
      The median effective concentration (EC50) from the dose-response curves of
      glucose uptake was the same on both groups of animals. Glucose oxidation and
      incorporation into lipids was also enhanced by salt overload. High salt increased
      insulin receptor density (P < .001). In conclusion, salt overload increased blood
      pressure, and high and low salt dietary content did not influence insulin
      sensitivity based on the unchanged EC50 from the in vitro studies. However,
      insulin-independent glucose uptake, oxidation, and incorporation into lipids were
      enhanced in adipocytes from rats on the high salt diet. The lower levels of
      insulin during the glucose tolerance test on salt-loaded animals may be a
      consequence of the higher insulin-independent glucose uptake in that group.

PMID- 9234826
TI  - A comparison of 24-h average blood pressures and blood pressure load following
      exercise.
AB  - Although the use of 24-h ambulatory blood pressure monitoring has been
      recommended in the study of blood pressure and exercise, consistent results have
      not been found for average 24-h systolic or diastolic blood pressures. Systolic
      load and diastolic load (the percentage of pressures >140/90 mm Hg during daytime
      hours and >120/80 mm Hg during sleep) have recently been identified as an
      important variable, but has had limited use with exercise. The purpose of this
      study was to compare the average systolic and diastolic pressures to systolic and
      diastolic loads from 24-h data recorded after a 50-min treadmill walk at 50%
      VO2max to data from a nonexercise control day. Subjects were 36 normotensive
      (116.9 +/- 10.7/77.0 +/- 8.9 mm Hg) and 25 hypertensive (141.0 +/- 13.7/96.6 +/-
      9.0 mm Hg) adults. No significant differences were found for systolic and
      diastolic pressures or loads between the control and exercise days for
      normotensives. Even though no significant changes were found for any of the
      average systolic and diastolic pressures between the control and exercise days
      for the hypertensives, significant reductions were found in systolic load for 24
      h (-25.7%), day (6 AM to 10 PM, -23.1%), work (6 AM to 5 PM, -22.9%), and leisure
      (5 PM to 10 PM, -26.7%) periods; and in diastolic load for the work (-22.5%)
      period. Thus, the measurement of systolic and diastolic load may be more
      sensitive than average systolic and diastolic blood pressures for the detection
      of 24-h ambulatory blood pressure changes with exercise in borderline
      hypertension.

PMID- 9234827
TI  - Dose-response characteristics of mibefradil, a novel calcium antagonist, in the
      treatment of essential hypertension.
AB  - The aim of this study was to determine the dose-response characteristics of the
      calcium antagonist, mibefradil, and to evaluate its antihypertensive efficacy and
      safety in varying doses in patients with mild-to-moderate hypertension. Three
      hundred and three eligible patients were randomized to receive once-daily 6.25-,
      12.5-, 25-, 50-, 100-, 150-, or 200-mg mibefradil doses or placebo for 4 weeks.
      Repeated blood pressure measurements and electrocardiographic recordings were
      obtained for the 24 h following the last dose of the placebo run-in period and
      for the first and last doses of randomized treatment. A statistically significant
      (P < .001 versus placebo) and clinically relevant drop in sitting diastolic blood
      pressure (SDBP) both at trough and at peak was observed in the 50-, 100-, 150-,
      and 200-mg mibefradil dose groups (trough placebo-corrected reductions: -4.9, 
      9.1, -9.9, and -11.9 mm Hg, respectively), with a significant dose-response
      relationship (P < .001) and high response rates. Trough/peak ratios for the
      placebo-corrected change from baseline to week 4 in SDBP were >85% for the 50-
      and 100-mg doses and 68% and 69% for the 150- and 200-mg doses, respectively. The
      full antihypertensive effect of mibefradil was achieved within 1 week of
      treatment. Reductions in sitting systolic blood pressure (SSBP) closely
      paralleled those in SDBP. The antihypertensive effect of mibefradil was
      associated with a slight dose-dependent decrease in heart rate and increase in
      the pulse rate (PR) electrocardiographic interval [corrected]. The appropriate
      therapeutic dose range of mibefradil in the management of mild-to-moderate
      essential hypertension is 50 to 100 mg.

PMID- 9234828
TI  - Additive effects of diltiazem and lisinopril in the treatment of elderly patients
      with mild-to-moderate hypertension.
AB  - A multicenter, double-blind, placebo-controlled trial with multifactorial design
      was conducted to evaluate the safety and efficacy of the calcium-channel blocker
      diltiazem, in a sustained release preparation, and the angiotensin converting
      enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with
      mild-to-moderate hypertension. In addition to the hypotensive effects of
      combinations of both drugs compared with monotherapy, all given once daily, the
      effect on quality of life was also evaluated. This study consisted of a 3 x 2
      multifactorial design in which 156 women and men with a sitting diastolic
      pressure of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout phase,
      were randomized to one of six treatment groups for 12 weeks of active treatment.
      Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of
      systolic and diastolic blood pressure. Compared with placebo, lisinopril 10 mg
      had an effect intermediate between the diltiazem doses. The combinations of
      diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg
      showed increased efficacy in reducing systolic and diastolic blood pressure
      compared to these drug doses used in monotherapy, but the effect of the
      combinations was less than predicted by an additive model. Although the total
      number of other adverse events reported was similar for all active treatment
      groups compared to placebo, lisinopril-induced cough was common with an incidence
      of 31% after rechallenge. Premature drug withdrawal was necessary in four of 78
      patients receiving lisinopril, due to intractable cough. The combination of
      diltiazem 240 mg and lisinopril 10 mg was significantly more effective at
      reducing blood pressure than either drug alone; this additive effect did not
      result in a higher rate of adverse effects or impairment of quality of life.
      Thus, combination therapy with these agents was well tolerated and resulted in
      increased efficacy in these elderly patients.

PMID- 9234829
TI  - Effects of cicletanine on prostaglandin I2 and E2 levels in patients with
      essential hypertension.
AB  - Cicletanine is a new antihypertensive drug that seems to stimulate the synthesis
      of prostaglandin (PG) I2. However, there is little evidence that cicletanine
      increases the level of PGI2 in the systemic blood of human subjects long-term. To
      investigate the antihypertensive mechanism of cicletanine, we measured serially
      the systemic blood pressure and the levels of both 6-keto-PGF1alpha (a stable
      metabolite of PGI2) and PGE2 in plasma and urine after administration of
      cicletanine. Nine patients with essential hypertension on a diet with sodium
      intake of 120 mEq/day took 100 mg of the drug orally daily every day for 1 week.
      Systemic blood pressure was measured hourly for 24 h on day 7 of the control
      period and on days 1 and 7 of the cicletanine period. The two PGs of interest
      were extracted, purified by high pressure liquid chromatography, and measured by
      radioimmunoassay. Cicletanine decreased blood pressure without reflexial
      tachycardia. The plasma levels of 6-keto-PGF1alpha were slightly, but
      significantly, higher at 3 h after the administration of cicletanine on both days
      1 and 7 of administration (on day 1, 3.88 +/- 1.44 pg/mL and on day 7, 4.07 +/-
      0.76, means +/- SD, both P < .05 v before administration on day 1) than before
      administration on day 1 (3.21 +/- 1.25 pg/mL). Plasma PGE2 was higher before and
      at 3 h after administration on day 7 than at 12 noon on day 7 of the control
      period. Cicletanine increased the urinary excretion of the two PGs; the increased
      PG levels partly account for the increased natriuresis in the first 3 days. The
      antihypertensive effects of cicletanine taken for 1 week were based on
      natriuresis caused by increased systemic synthesis of the vasodilator PGI2 and
      partly by the increased renal synthesis of PGI2 and PGE2.

PMID- 9234830
TI  - What time is the "biologic zero hour" of circadian variability?
AB  - Most ambulatory blood pressure monitoring (ABPM) studies have used a mechanical
      clock as the reference time, but there is no biologic background for assuming
      that midnight by the mechanical clock is zero hour by the biologic clock. The aim
      of this study was to determine the biologic zero hour as the zero reference time
      by evaluating the circadian rhythm of blood pressure, heart rate, and activity.
      Twenty healthy medical students (18 men, 2 women, mean age 26 years old) were
      recruited and blood pressure, heart rate, and physical activity were monitored
      simultaneously by an ABPM device every 30 min for 48 h. Four concepts of zero
      time were selected in this study and analyzed regarding biologic zero hour: 24:00
      by the mechanical clock (clock time); the time of awakening, based on a diary
      (diary time); the time of a sudden increment in physical activity in the morning
      (activity time); and the middle of the total sleeping time, based on the diary
      (midsleeping time). The awakening time is a better individual index than the
      mechanical clock, and the midsleeping time as the zero reference point is better
      than the awakening time. We assessed the reproducibility of the data regarding
      the circadian troughs between the first and second day. The reproducibility of
      the day-to-day variation of the blood pressure and heart rate was poor. The
      reproducibility of physical activity was fairly good, but the magnitude of
      activity was small. A 48-h monitoring profile is superior to a 24-h monitoring
      period.

PMID- 9234831
TI  - Endothelium-derived hyperpolarizing factor: characterization as a cytochrome P450
      1A-linked metabolite of arachidonic acid in perfused rat mesenteric prearteriolar
      bed.
AB  - The isolated perfused rat mesenteric bed releases endothelium-derived
      hyperpolarizing factor (EDHF) in response to acetylcholine (ACh) or histamine. I
      propose that EDHF released in the mesenteric vascular bed is a cytochrome P450
      (CYP)-linked, arachidonate metabolite. In the presence of nitro-L-arginine methyl
      ester (L-NAME) and indomethacin, injections of ACh (0.001 to 10 nmol) or
      histamine (0.1 to 1,000 nmol) elicited transient, dose-dependent dilation of
      cirazoline (an alpha1-adrenoceptor selective agonist) preconstricted mesenteric
      beds. The L-NAME-resistant responses to ACh or histamine were insensitive to
      tetrodotoxin (1 micromol/L), thus negating its neuronal origin, but were
      profoundly attenuated by a K+ channel inhibitor tetrabutylammonium (0.5 mmol/L).
      7-Ethoxyresorufin (a selective and competitive blocker of CYP 1A isozyme) blunted
      ACh and histamine mediated EDHF responses but did not alter vasodilation
      initiated through K+ channel activation by either cromakalim or NS-1619, or
      through the nitric oxide-cGMP pathway (sodium nitroprusside). Clotrimazole, an
      imidazole that inhibits CYP by binding to the heme moiety, attenuated ACh,
      histamine, and cromakalim but not sodium nitroprusside-mediated vasodilator
      responses. Other CYP isozyme selective inhibitors, such as metyrapone (CYP 2B), 7
      pentoxyresorufin (CYP 2B1), sulfaphenazole (CYP 2C/3A), and 17-octadecynoic acid
      (4A-linked omega-hydroxylase inhibitor), did not alter ACh or histamine-induced
      EDHF response. The EDHF-mediated dilations initiated by ACh and histamine, as
      well as K(ATP) activation by cromakalim, were blocked by mepacrine, a
      nonselective phospholipase A2 inhibitor. Mepacrine did not alter K(Ca) activation
      by compound NS-1619. I conclude that 1) the isolated perfused rat mesenteric
      prearteriolar bed releases in response to ACh and histamine, an EDHF that causes
      vasodilation through K+ channel activation; 2) the EDHF is most likely a CYP
      derived arachidonate product; 3) CYP 1A is well suited as the isozyme responsible
      for EDHF production in this vascular bed; and 4) PLA2 appears to mediate the
      release of the precursor arachidonic acid.

PMID- 9234833
TI  - Inhibitory effect of monatepil maleate on acyl-CoA:cholesterol acyltransferase
      activity in the liver of cholesterol-fed Japanese monkeys.
AB  - We have previously demonstrated that monatepil maleate, AJ-2615, a new calcium
      antagonist endowed with alpha1-adrenoceptor blocking property, has
      antiatherosclerotic and plasma lipid-lowering effects in Japanese monkeys fed on
      a cholesterol-rich diet. To clarify the mechanisms on plasma lipid-lowering
      action, we investigated the effect of monatepil maleate in these monkeys on
      hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity. Both ACAT activity
      and esterified cholesterol content in the livers of monkeys fed on a cholesterol
      rich diet for 6 months significantly increased about 7- and 16-fold,
      respectively, as compared with those in monkeys fed on a standard diet. Monatepil
      maleate (30 mg/kg/day for 6 months, orally) inhibited the increases of ACAT
      activity and esterified cholesterol content by 51% and 71%, respectively. In in
      vitro experiments, monatepil maleate inhibited ACAT activity in a concentration
      dependent manner, whereas it did not affect 3-hydroxy-3-methylglutaryl-CoA (HMG
      CoA) reductase activity. A kinetic analysis revealed that monatepil maleate was a
      noncompetitive type inhibitor of ACAT. Hepatic ACAT activity was significantly
      correlated to hepatic esterified cholesterol content (r = 0.775, P < .0001), to
      plasma very low density lipoprotein (VLDL) content (r = 0.765, P < .0001) and to
      plasma total cholesterol content (r = 0.573, P < .005) in the monkeys. These
      results suggest that ACAT-inhibiting effect of monatepil maleate plays an
      important role in the reduction of hyperlipidemia.

PMID- 9234832
TI  - Effects of erythropoietin administration on blood pressure and urinary albumin
      excretion in rats.
AB  - The effects of recombinant human erythropoietin (rHuEPO) administration on blood
      pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto
      rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated
      with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in
      metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a
      week) for 6 weeks. Control animals received the vehicle only (0.25 mL of
      physiological saline). An angiotensin converting enzyme inhibitor was
      administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic
      blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once
      a week. No significant differences in SBP were observed between rHuEPO and
      vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v
      172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher
      in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/-
      7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg,
      respectively); UAE was significantly higher in groups treated with rHuEPO than in
      control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4
      +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v
      143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin
      treatment causes an increase in arterial pressure in SHR only, and an increase in
      UAE in both normotensive and hypertensive rats. The albuminuric effect was not
      entirely dependent on increased blood pressure. The treatment with an angiotensin
      converting enzyme inhibitor did not modify either the proteinuric or the pressor
      effects.

PMID- 9234834
TI  - Angiotensin converting enzyme gene polymorphism in essential hypertension based
      on ambulatory blood pressure monitoring.
AB  - The association of the angiotensin converting enzyme (ACE) gene polymorphism with
      essential hypertension is still controversial. We studied its polymorphism in 41
      patients with hypertension based on ambulatory blood pressure (ABP) and 34
      subjects with normal blood pressure. The ACE genotype was not significantly
      different between hypertensive and normotensive subjects. Casual blood pressure
      levels, 24 h, and daytime and nighttime ABP levels did not differ among the ACE
      genotype in patients with hypertension. In conclusion, the ACE genotype is not
      associated with essential hypertension based on ABP monitoring.

PMID- 9234835
TI  - Mid- and long-term reproducibility of noninvasive measurements of spontaneous
      arterial baroreflex sensitivity in healthy volunteers.
AB  - Baroreflex sensitivity (BRS) is altered in a variety of circumstances and could
      be considered as a marker for the prognosis of some cardiovascular diseases. The
      present study was designed to evaluate the reproducibility of noninvasive
      measures of BRS, both at mid- and at long-term. Fourteen healthy volunteers were
      examined on three occasions (first interval = 1 week, second interval = 1 year).
      Each recording was performed using a noninvasive photoplethysmographic device
      (Finapres 2300, Ohmeda), both in supine and standing positions. Two different
      methods of measurement were used: the sequences method and cross spectral
      analysis. The reproducibility of BRS measures was as satisfactory at mid- as at
      long-term for the sequences method (intraclass coefficient [ICC] = 0.87 and 0.86,
      respectively), but it was better at mid- than at long-term for the cross-spectral
      analysis (ICC = 0.85 and 0.54, respectively). The measures performed in standing
      position were obviously more reproducible than those made in recumbent position
      (ICC = 0.87 and 0.70 for the sequences method, 0.85 and 0.71 for the cross
      spectral analysis, respectively). Due to the high reproducibility of these
      noninvasive measures, the number of patients to be included in a pharmacological
      study was calculated as rather small: for example, only 20 patients are required
      for detecting a change in upright BRS of 3 msec/mm Hg, at long-term (sequences
      method). Likewise, the magnitude of the regression to the mean, which has to be
      expected in patients selected for a follow-up study, turned out to be low: for
      example, <15% of the difference between the patient group mean value and the
      reference value, both at mid- and at long-term (standing position, sequences
      method). We conclude that: 1) The noninvasive measures of BRS in standing
      position are reproducible enough to allow longitudinal studies to be conducted
      over either a short or a long period; 2) The long-term reliability of the
      sequences method seems to be higher than that of the cross-spectral analysis; and
      3) Subtle changes in SBR may be noninvasively detected within small patient
      groups.

PMID- 9234836
TI  - Reproducibility of home blood pressure measurements over a 1-year period.
AB  - We compared the reproducibility over time of blood pressure measured at the
      health examinations (screening blood pressure) and blood pressure measured at
      home (home blood pressure). Both screening and home blood pressure were measured
      in subjects of a rural community. Subjects measured their own blood pressure at
      home once in the morning using a semiautomatic oscillometric blood pressure
      measuring device at least three times (on at least 3 days) in each of two 4-week
      periods separated by one year. Similarly, two screening blood pressure
      measurements were obtained from the subjects at each of two health examinations
      also taken 1 year apart. A total of 136 untreated subjects without cardiovascular
      complications (40 men and 96 women, 56 +/- 11.7 years, mean +/- SD) were analyzed
      in the study. The correlations between the first and second blood pressure
      measurements of the subjects were significantly higher for the home blood
      pressure measurements (systolic: r = 0.844 and diastolic: r = 0.830) than for the
      screening blood pressure measurements (systolic: r = 0.692 and diastolic: r =
      0.570). The mean differences between the first and second home blood pressure
      (0.8 +/- 7.7 mm Hg for systolic BP and 0.9 +/- 5.5 mm Hg for diastolic BP) were
      significantly smaller than those for the screening blood pressure (-3.9 +/- 13.8
      for systolic BP and -3.1 +/- 10.2 for diastolic BP) (P < .001 for both
      comparisons), suggesting that the reproducibility of home blood pressure over
      time is superior to that of screening blood pressure. Such reliable blood
      pressure measurements obtained at home have a clinical significance for the
      diagnosis and treatment of hypertension and as a tool for evaluating the efficacy
      of antihypertensive drugs. Home blood pressure measurements also may be more
      useful than screening blood pressure measurements in predicting future
      cardiovascular events.

PMID- 9234837
TI  - Hypertension in blacks.
AB  - The excess of hypertension among blacks has been recognized since early in this
      century and explains a substantial portion of the black health disadvantage. In a
      cohort study begun in the 1970s, hypertension accounted for 20% of all-cause
      mortality among blacks, compared to 10% among whites. National data on trends in
      hypertension (140/90 mm Hg or treatment) prevalence from 1960 to 1990 suggest a
      decline from 44% to 32%, although differences in survey technique likely account
      for this pattern. During this period the prevalence ratio of black:white remained
      constant at 1.5, suggesting that secular trends in causal factors, if any,
      effected both groups equally. Recent data demonstrate a gradient in risk across
      the African diaspora, with standardized prevalences of 14% in West Africa and 26%
      in the Caribbean, compared to 33% in the US. This pattern parallels the gradient
      in known risk factors, with obesity alone accounting for a third of the excess in
      the US compared to Africa. Why the black excess of hypertension in the US?
      Despite widespread speculation, unique characteristics of hypertension among
      blacks have yet to be established. Consistent evidence demonstrates a similar
      impact of the known risk factors in all population groups. Epidemiologic evidence
      likewise suggests that a similar risk of complications exists with blood pressure
      elevation among blacks and whites, level for level. Although the genetic
      epidemiology of hypertension is still in its infancy, no clear cross-population
      differences are yet apparent. Pathophysiologic traits that are known to be part
      of the causal etiologic pathway have not been shown to vary across groups. Unique
      features of this condition among blacks are likely to be restricted to the
      different mixes and intensities of risk factors. In the absence of evidence to
      support the hypothesis, it is perhaps surprising that credence continues to be
      given to the notion of black exceptionalism. Am J

PMID- 9234838
TI  - Detection of preclinical atherosclerosis may optimize the management of
      hypertension.
AB  - Because of the limited ability of blood pressure elevation to predict risk, the
      mass drug treatment of hypertension above an arbitrary threshold may result in
      many subjects being overtreated. One potential way to overcome this problem is to
      noninvasively detect preclinical atherosclerosis. Hypertension has been shown to
      be associated with 1) increased intima-media thickness and more frequent plaques
      in extracoronary arteries, 2) more frequent calcifications in coronary arteries,
      3) increased wall rigidity in the aorta and peripheral arteries, and 4) impaired
      endothelium dependent vasodilation and abnormal blood rheology, which are capable
      of promoting the conversion of atherosclerosis into atherothrombosis. The
      prognostic significance of these markers of preclinical atherosclerosis is
      supported by evidence of their association with numerous risk factors, and
      prevalence and incidence of cardiovascular damages. Preclinical arterial lesions
      also constitute ideal targets to test whether antihypertensive treatment can
      reverse or slow down arterial disease, and whether such a reversal produces
      better prevention than simply lowering blood pressure. Finally, the detection of
      atherosclerosis applied to large populations of mildly hypertensive subjects
      safely and at relatively low cost could help to better target the pharmacological
      treatment, given that a substantial proportion of subjects without evidence of
      preclinical disease may be suitable for nondrug treatment.

PMID- 9234839
TI  - The role of endothelin-1 in hypertension.

PMID- 9234840
TI  - Humoral factors and blood pressure in DOCA-salt hypertensive rats.

PMID- 9234841
TI  - Mild-to-moderate hypertension and apolipoprotein E gene polymorphism.

PMID- 9234842
TI  - Determination of plasma Ntau-methylhistamine in vivo by isotope dilution using
      benchtop gas chromatography-mass spectrometry.
AB  - A practical sensitive and specific method for determination of the stable
      metabolite of histamine, Ntau-methylhistamine, in human plasma using benchtop gas
      chromatography-stable isotope dilution mass spectrometry has been developed. Ntau
      Methylhistamine, a principal metabolite of histamine in humans, was extracted and
      purified from human plasma using a two-step procedure with Sep-Pak silica
      cartridges. Quantitation of Ntau-methylhistamine was made possible by the
      synthesis of Ntau-[2H3]methylhistamine used as an internal standard.
      Derivatization with pentafluoropropionyl anhydride of extracts of human plasma
      yielded the bis-pentafluoropropionyl derivative of Ntau-methylhistamine for
      measurement using selected ion monitoring of the m/z 417/420 ion pair after
      electron impact on a benchtop gas chromatography-mass spectrometry (GC-MS). By
      improvements in the plasma extraction technique, inclusion of a synthetic
      internal standard and the development of a sensitive and stable derivative of the
      histamine metabolite, Ntau-methylhistamine was found to be significantly elevated
      in the plasma of patients with the dermal fibroproliferative disorder,
      hypertrophic scarring as compared to age-matched normal volunteers (98.5+/-29.5
      pg/ml, n=9, versus 43.3+/-16.5 pg/ml, n=8, p<0.05). As such, this method affords
      a sensitive, specific and practical approach to measurement of histamine
      metabolites in plasma and other biological fluids.

PMID- 9234843
TI  - In situ derivatisation and extraction of volatile fatty acids entrapped on anion
      exchange resin from aqueous solutions and urine as a test matrix using
      pentafluorobenzyl bromide in supercritical carbon dioxide.
AB  - The simultaneous extraction and derivatisation of anion-exchange resin-trapped
      volatile fatty acids (C2-C5) as their pentafluorobenzyl esters has successfully
      been performed under CO2 supercritical fluid extraction conditions. Volatile
      fatty acid standards of acetic, propionic and n-butyric acids (at 20 and 100 ppm)
      as their ester derivatives were recovered at 78.0-101.5% (C.V. 3.5-7.5%, n=6 and
      7). Likewise, acrylic acid recoveries were 57.0-61.0% (C.V. 5.5-5.6%, n=6 and 7).
      This methodology was applied to the quantitation of acetic, propionic, n-butyric
      and n-valeric acids in spiked urine as a test matrix. Initial clean-up of
      phosphate and sulfate in the urine was required prior to anion-exchange
      application and this was achieved by barium salt precipitation. Recoveries ranged
      from 36 to 66.5% (C.V. 5.9-14.4%, n=9 and 6).

PMID- 9234844
TI  - Quantitative analysis of two opioid peptides in plasma by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - Quantitative analysis of two opioid peptides, DSLET [(D-Ser2)Leu-enkephalin-Thr6]
      and Met-enkephalin-Arg-Gly-Leu, was performed using microbore liquid
      chromatography interfaced to electrospray ionization tandem mass spectrometry.
      Validation of the methodology was demonstrated for each peptide in plasma.
      Quantitative analyses were performed through the use of a deuterium labelled
      peptide analog as an internal standard. Linearity was observed for the analysis
      of DSLET (5-1000 ng/ml) and Met-enkephalin-Arg-Gly-Leu (1-1000 ng/ml) in plasma
      with a limit of detection of 0.25 ng/ml for Met-enkephalin-Arg-Gly-Leu and 1.0
      ng/ml for DSLET. In general, the observed concentrations showed good
      reproducibility with coefficients of variation of within 15%. In the
      concentration range studied, only 0.5 ml of plasma was required for optimal
      detection of Met-enkephalin-Arg-Gly-Leu and 0.25 ml for DSLET. Application of
      this method was demonstrated by studying the disposition of DSLET in a rat. DSLET
      administered to a rat exhibited a short half-life and a high clearance value.

PMID- 9234845
TI  - Reversed-phase high-performance liquid chromatography of radioiodinated salmon
      calcitonins.
AB  - Reversed-phase HPLC conditions for simultaneous separation of salmon calcitonin,
      mono- and di-radioiodinated salmon calcitonins and their tryptic digested
      fragments have been developed. Salmon calcitonin was radioiodinated with Na125I
      by the iodo-beads method. After solid-phase extraction from the reaction mixtures
      using C18 Bond Elut cartridges, mono- and di-radioiodinated salmon calcitonins
      were separated from each other, as well as from unlabeled salmon calcitonin, on a
      Bondclone 10 C18 column (300x7.8 mm I.D.) by isocratic elution with 0.1%
      trifluoroacetic acid in 34% aqueous acetonitrile. The characteristics of either
      iodinated peptides or unlabeled salmon calcitonin were evaluated on the basis of
      UV absorbance (215 and 280 nm), fluorescence (lambda(ex)=282 nm, lambda(em)=310
      nm) and measurement of specific radioactivity by means of a flow-through radio
      isotope detector. HPLC separation of a tryptic digest of iodinated salmon
      calcitonin fraction on a W-porex 5 C18 300 A column (250x4.6 mm I.D.) and
      subsequent amino acid analysis, led to the conclusion that radioiodination took
      place at the Tyr residue and not at the His moiety.

PMID- 9234846
TI  - New support for the affinity chromatography of hemoglobin.
AB  - A new support for affinity chromatography of hemoglobin was synthesised from EAH
      Sepharose-4B containing a hexamethylamine spacer. Benzenetetracarboxylic (BTC) or
      benzenehexacarboxylic (BHC) acids were covalently bound to the spacer arm. At pH
      close to the pI of the protein, the biospecificity of the support due to the
      interactions of the allosteric site of hemoglobin with immobilised polyanionic
      ligands was proved. When the allosteric site was blocked by covalently linked
      pyridoxalphosphate, the protein showed no more affinity for the support. Further
      investigations were done on the BHC support; the association constants between
      BHC support and the hemoglobin forms, oxyhemoglobin and deoxyhemoglobin, were
      determined. The deoxyhemoglobin affinity was ten times higher than that of
      oxyhemoglobin, both for fixed and for free ligand. The following values of
      binding constants K(PX) and K(PL) (1 mol(-1)) with fixed or free ligand
      respectively were found: for oxyhemoglobin, K(PX)=8.0x10(2), K(PL)=1.4x10(4); for
      deoxyhemoglobin, K(PX)=9.7x10(4), K(PL)=2.3x10(5). The BHC support capacity was
      about 4.7x10(-5) mol hemoglobin g(-1) of dry gel corresponding to 1.5x10(-6) mol
      hemoglobin g(-1) of hydrated gel or 0.1 g hemoglobin g(-1) of hydrated gel.

PMID- 9234847
TI  - Simultaneous isolation of protein C activator, fibrin clot promoting enzyme
      (fibrozyme) and phospholipase A2 from the venom of the southern copperhead snake.
AB  - The simultaneous isolation of three enzymes from the southern copperhead snake
      venom (Agkistrodon contortrix contortrix; ACC) is described. The first step is a
      chromatography of crude venom on a Mono S cation-exchange column at pH 6.5. A
      fibrin clot promoting enzyme (fiprozyme) that preferentially releases
      fibrinopeptide B from fibrinogen is isolated from the fraction not binding to the
      Mono S by a further three-step process. The procedure involves affinity
      chromatography on Blue Sepharose, gel chromatography on Sephacryl S-200 and metal
      chelate chromatography on Chelating Sepharose. Protein C activator and
      phospholipase coelute from the Mono S column. They are separated by a gel
      chromatography on Sephacryl S-200. After this step two enzymes are obtained: a
      highly purified protein C activator applicable in methods for determination of
      functional level of protein C (a plasma regulator of hemostasis) and an
      electrophoretically pure enzyme with the activity of phospholipase A2.

PMID- 9234848
TI  - Ion-pair liquid chromatography-electrospray mass spectrometry for the analysis of
      cyclic nucleotides.
AB  - An LC-MS method has been developed combining ion-pair chromatography with an
      electrospray interface linking microbore and capillary HPLC to mass spectrometry.
      Separation of cyclic nucleotides on C18 reversed-phase columns, using
      tetrabutylammonium bromide as an ion pairing agent was evaluated with different
      mobile phase compositions. It was found that low ion-pairing agent concentration
      (50-500 microM) used in combination with low flow-rates (5-10 microl min(-1))
      allowed the system to operate for up to several days without observing a reduced
      signal caused by source pollution. The loss of sensitivity expected in ion-pair
      chromatography could be remedied by using a 2-propanol coaxial sheath flow.
      Optimal conditions for negative ion electrospray resulted in a linear detection
      response in the femtomole to picomole range. Using biological samples this method
      was evaluated and compared with a classical ion-suppression RP-HPLC method using
      UV detection.

PMID- 9234849
TI  - Detection of N7-(2-hydroxyethyl)guanine adducts in DNA and 9L cells treated with
      1-(2-chloroethyl)-1-nitrosourea.
AB  - A sensitive analytical method, HPLC-ED, was developed for the measurement of N7
      (2-hydroxyethyl)guanine (N7-HOEtG). A detection limit of 3.2 N7-HOEtG/10(8)
      nucleotides was obtained with this method. Linear dose response curves for the
      formation of N7-HOEtG were obtained following treatment of either calf thymus DNA
      or 9L cells with 1-(2-chloroethyl)-1-nitrosourea (CNU). Using HPLC-ED a
      significant increase in the level of N7-HOEtG could be detected in 9L cells
      following treatment with 5 microM CNU. Our study suggests that with this
      analytical method the formation of N7-HOEtG in the white blood cells of patients
      treated with chloroethylnitrosoureas may be determined.

PMID- 9234850
TI  - Simultaneous measurement of seven carotenoids, retinol and alpha-tocopherol in
      serum by high-performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatography (HPLC) procedure for the
      quantitative measurement in serum of seven carotenoids (lutein, zeaxanthin,
      canthaxanthin, beta-cryptoxanthin, lycopenes, alpha-carotene and beta-carotene),
      retinol, alpha-tocopherol and two internal standards (tocol and echinenone) has
      been developed. The geometric isomers, lutein and zeaxanthin, were completely
      separated as well as at least nine unidentified carotenoids. All compounds were
      resolved on an Adsorbosphere HS C18 (3 microm) column (250x4.6 mm I.D.) with a
      step gradient, 7.1 min after injection, from acetonitrile-methanol (60:40, v/v)
      containing 0.05% acetic acid to acetonitrile-methanol-dichloromethane
      (45.6:30.4:24, v/v) containing 0.04% acetic acid, in a total run time of 23 min.
      Chromatograms at four different wavelengths (292, 325, 450 and 473 nm) and
      spectra were monitored with a diode array detector. Because of its specificity
      and sensitivity for a large number of carotenoids, this procedure may be of
      interest for nutritional and epidemiological studies. Its speed and robustness
      make it suitable for analyses on large numbers of subjects.

PMID- 9234851
TI  - Simultaneous analysis of retinol, all-trans- and 13-cis-retinoic acid and 13-cis
      4-oxoretinoic acid in plasma by liquid chromatography using on-column
      concentration after single-phase fluid extraction.
AB  - A reversed-phase high-performance liquid chromatographic method for the
      simultaneous analysis of retinol, all-trans-retinoic acid, 13-cis-retinoic acid
      and 13-cis-4-oxoretinoic acid in human plasma and cell culture medium is
      described. Sample preparation involves precipitation of proteins and extraction
      of retinoids with 60% acetonitrile. After centrifugation, the acetonitrile
      content of the supernatant is reduced to 45%, allowing on-column concentration of
      analytes. Injection volumes up to 2.0 ml (equivalent to 0.525 ml of sample) can
      be used without compromising chromatographic resolution of all-trans-retinoic
      acid and 13-cis-retinoic acid. Retinoids were stable in this extract and showed
      no isomerization when stored in the dark in a cooled autosampler, allowing
      automated analysis of large series of samples. Recoveries from spiked plasma
      samples were between 95 and 103%. Although no internal standard was used, the
      inter-assay precision for all retinoids was better than 6% and 4% at
      concentrations of 30 nM and 100 nM, respectively. The method is a valuable tool
      for the study of cellular metabolism of all-trans-retinoic acid, as polar
      metabolites of this compound can be detected with high sensitivity in cell
      culture media.

PMID- 9234852
TI  - Biological monitoring of occupational exposure to 1-methoxy-2-propanol.
AB  - At the end of a workweek 23 silkscreen printers gave a urine sample for capillary
      gas chromatographic analysis for 1,2-propanediol. The mean concentration was 2.52
      (S.D. 2.01) mmol mol creatinine(-1) (median=1.76, n=23). The urinary excretion of
      1,2-propanediol was linearly dependent on the preceding 1-methoxy-2-propanol
      exposure measured in the worker's breathing zone [y=0.99+0.28x, n=23, r=0.67,
      where y is the urinary 1,2-propanediol concentration, in mmol mol creatinine(-1)
      and x is the concentration, in cm3 m(-3), of 1-methoxy-2-propanol (90.2%), 1
      ethoxy-2-propyl acetate (5.8%), 1-methoxy-2-propyl acetate (2.1%) and 1-ethoxy-2
      propanol (1.9%) in the air].

PMID- 9234853
TI  - Development of a high-performance liquid chromatography retention index scale for
      toxicological drug screening.
AB  - An efficient and practical analytical method for correcting HPLC retention data
      has been produced using an HPLC diode-array UV detector system. The system is
      based on retention indices (RI) and is to be used primarily for the
      identification of toxicologically relevant drugs involved in clinical and
      forensic toxicology. The RI correction method was chosen as it provided a
      slightly greater degree of reproducibility than using relative retention time
      (RRT), particularly for acidic and neutral drugs. Development of the system
      involved the establishment of the optimal chromatographic conditions and
      extensive studies of the stability of the system. An acetonitrile gradient
      elution was used with RI values determined by interpolation from a series of
      specifically chosen basic and acidic/neutral marker drugs which eluted at regular
      intervals to produce a linear RI scale. It was found that two separate RI scales
      were required for basic and acidic/neutral drugs. The use of multiple drug
      markers as primary retention index standards had not been previously applied to
      HPLC general drug screening and comparison with a recently published database
      suggests that the system may also provide improved selectivity.

PMID- 9234854
TI  - Assay for valproic acid and its E-delta2 metabolite in rat plasma by capillary
      gas chromatography without prior derivatization.
AB  - A new and improved gas chromatographic assay method for valproic acid and a
      metabolite, E-delta2 valproic acid, in rat plasma has been developed. The assay
      has sufficient sensitivity to measure free levels of the parent drug and
      metabolite. By employing a Stabilwax-DA capillary column, symmetrical
      chromatographic peaks were obtained without the need for prior derivatization.
      Standard curves for valproic acid were linear from 0.1 to 640 microg/ml. Standard
      curves for the metabolite were linear from 0.1 to 556 microg/ml.

PMID- 9234856
TI  - Simultaneous determination of a potassium channel opener and its metabolite in
      rat plasma with column-switching liquid chromatography using atmospheric pressure
      chemical ionisation.
AB  - A specific LC-MS assay was developed for simultaneous determination of Ro 31-7837
      (I) and its metabolite Ro 31-6930 (II) in rat plasma, using on-line SPE by column
      switching reversed-phase HPLC combined with atmospheric pressure chemical
      ionization (APCI) tandem mass spectrometry for detection in the selected reaction
      monitoring mode. The method involved precipitation of plasma proteins with
      ethanol and automatic injection of a 1-ml aliquot of the supernatant onto a
      standard bore trapping column (LC-ABZ, 20x4.6 mm) for compound retention. Using
      the backflush mode, the analytes were transferred onto the analytical column
      (Kromasil C18, 125x4.0 mm) for chromatographic separation and mass spectrometric
      detection. The mean precision and accuracy for I and II in the concentration
      range 0.25-100 ng/ml were found to be 3.7% and 101%, and 3.5% and 106%,
      respectively. The data were assessed from QC samples during the validation phase
      of the assay. The lower limit of quantification for both I and II was 0.25 ng/ml,
      using a 0.5-ml plasma aliquot. This LC-MS method provided the requisite
      specificity, sensitivity, accuracy and precision to assess the pharmacokinetics
      of the compounds in the rat.

PMID- 9234855
TI  - Use of reduced sorbent bed and disk membrane solid-phase extraction for the
      analysis of pharmaceutical compounds in biological fluids, with applications in
      the 96-well format.
AB  - Significant improvements in the isolation of pharmaceutical compounds from
      plasma, serum and urine, have been achieved using ultra low mass sorbent bed and
      thin disk solid-phase extraction (SPE) material. The use of low sorbent masses or
      disk SPE material has allowed a significant reduction in solvent usage and
      extraction times. The reduction in solvent volumes required has allowed elution
      volumes to be reduced to as low as 30 microl with high and consistent analyte
      recovery. Several SPE RP-HPLC methods have been developed using these materials,
      including LC-MS methods. When the chromatographic conditions allow the eluent to
      be injected directly or injected after dilution with distilled water Empore disks
      are the extraction media of choice due to the materials low elution volume
      requirements. When operated in the 96-well microtitre format this micro
      extraction provides a very efficient throughput and requires little sample
      manipulation.

PMID- 9234857
TI  - Determination of ticarcillin epimers in plasma and urine with high-performance
      liquid chromatography.
AB  - A high-performance liquid chromatogaphic method was developed for determining the
      concentrations of ticarcillin (TIPC) epimers in human plasma and urine. Samples
      were prepared for HPLC analysis with a solid-phase extraction method and the
      concentrations of TIPC epimers were determined using reversed-phase HPLC. The
      mobile phase was a mixture of 0.005 M phosphate buffer (pH 7.0) and methanol
      (12:1, v/v) with a flow-rate of 1.0 ml/min. TIPC epimers were detected at 254 nm.
      Baseline separation of the two epimers was observed for both plasma and urine
      samples with a detection limit of ca. 1 microg/ml with a S/N ratio of 3. No peaks
      interfering with either of the TIPC epimers were observed on the HPLC
      chromatograms for blank plasma and urine. The recovery was more than 80% for both
      plasma and urine samples. C.V. values for intra- and inter-day variabilities were
      0.9-2.1 and 1.1-6.4%, respectively, at concentrations ranging between 5 and 200
      microg/ml. The present method was used to determine the concentrations of TIPC
      epimers in plasma and urine following intravenous injection of TIPC to a human
      volunteer. It was found that both epimers were actively secreted into urine and
      that the secretion of TIPC was not stereoselective. Plasma protein binding was
      also measured, which revealed stereoselective binding of TIPC in human plasma.

PMID- 9234858
TI  - Stereoselective determination of a new antidepressant, E2011, and its
      diastereoisomer as a metabolite by high-performance liquid chromatography.
AB  - A stereoselective HPLC method has been developed for the determination of E2011
      (compound I) and one of its metabolites and diastereoisomers, ER-20593 (compound
      II), in plasma. The two substances and the internal standard were extracted from
      plasma, followed by two purification steps. In the first step, a minicolumn, Bond
      Elut C18, was used and in the second step, another minicolumn, Bond Elut Si, was
      used for purification of the compounds. After the purification, the compounds
      were analyzed by HPLC with two Chiralpak AD columns. In this procedure, compounds
      I and II were stable and there was no chiral inversion. The within-day and the
      between-day assays were performed in rat plasma, where compounds I and II existed
      simultaneously. The within-day and the between-day precisions of compound I were
      2.0 approximately 10.1% and 1.3 approximately 7.1%, and the within-day and the
      between-day accuracies were -8.2 approximately +3.0% and -6.6 approximately +4.0%
      in the concentration range 0.003-10 microg ml(-1). The within-day and the between
      day precisions of compound II were 1.7 approximately 16.9% and 0.9 approximately
      4.5% and the within-day and the between-day accuracies were -9.0 approximately
      +2.4% and -5.6 approximately +3.8% in the concentration range of 0.005-0.5 microg
      ml(-1). QC samples for compound I and II were stable for at least 3 months. The
      method was applied to measure the levels of compound I and II in the rat plasma
      after oral administration of compound I.

PMID- 9234859
TI  - Sensitive assay for pimozide in human plasma using high-performance liquid
      chromatography with fluorescence detection: application to pharmacokinetic
      studies.
AB  - A method is described for the measurement of pimozide in human plasma using HPLC
      with fluorescence detection. The method is specific and sensitive in the range of
      concentrations seen in human plasma after conventional dosing (1-15 ng/ml) with a
      limit of quantification of 1 ng/ml. The calibration curves are linear for
      concentrations between 1 and 50 ng/ml. Within-day and inter-day coefficients of
      variation are less than 7.4% and 15.5%, respectively, at three concentrations of
      pimozide (2, 10 and 20 ng/ml). Intra-day and inter-day bias are less than 18.5%
      and 12.5%, respectively. A pharmacokinetic study conducted in a healthy volunteer
      administered 6 mg of pimozide orally demonstrates the utility of this method.

PMID- 9234860
TI  - Stereospecific determination of an HIV aspartyl protease inhibitor, PNU-103017,
      in rat, dog and human plasma using a Pirkle-concept high-performance liquid
      chromatographic column.
AB  - A sensitive stereospecific high-performance liquid chromatographic assay for the
      quantitation of the enantiomers of 4-cyano-N-(3-(cyclopropyl-(5,6,7,8,9,10
      hexahydro-4-hydroxy-2-oxo-2H- cycloocta(b)pyran-3
      yl)methyl)phenyl)benzenesulfonamide (PNU-103017) (I), an HIV protease inhibitor,
      in plasma of rat, dog and human was developed. The procedure involved an
      acetonitrile-aided protein precipitation followed by solid-phase extraction (SPE)
      of I from plasma into ethanol. Stereospecific separation was accomplished on a
      Pirkle-concept chiral column (Regis S,S-Whelk-01, 250x4.6 mm I.D.) with a mobile
      phase of absolute ethanol-0.1% acetic acid in hexane (30:70, v/v). The eluate was
      monitored by UV absorbance (295 nm). Linear calibration curves were obtained in
      the range of 0.2 to 500 microM, with a lower limit of quantitation of 0.1-0.2
      microM for both enantiomers in either rat, dog or human plasma. Intra- and inter
      assay precision and assay accuracy were demonstrated to be acceptable for the
      stereoselective pharmacokinetic analysis of I in plasma.

PMID- 9234861
TI  - High-performance liquid chromatographic analysis of ondansetron enantiomers in
      human serum using a reversed-phase cellulose-based chiral stationary phase and
      solid-phase extraction.
AB  - A stereospecific HPLC method was developed for the assay of R-(-)- and S-(+)
      ondansetron enantiomers in human serum. The method involves the use of solid
      phase extraction for sample clean-up and is also free of interference from 6
      hydroxyondansetron, 7-hydroxyondansetron and 8-hydroxyondansetron, the three
      major metabolites of ondansetron. Chromatographic resolution of the enantiomers
      was performed on a reversed-phase cellulose-based chiral column (Chiralcel OD-R)
      under isocratic conditions using a mobile phase consisting of 0.7 M sodium
      perchlorate-acetonitrile (65:35, v/v) at a flow-rate of 0.5 ml/min. Recoveries at
      200 ng/ml levels were more than 90% for both ondansetron enantiomers. Intra-day
      and inter-day precisions calculated as R.S.D.s were in the 0.3-5% and 2-8% ranges
      for both enantiomers, respectively. Intra-day and inter-day accuracies calculated
      as percent error were in the 0.3-11.5% and 0-3% ranges for both enantiomers,
      respectively. Linear calibration curves were obtained for each enantiomer in
      serum in the concentration range 15-750 ng/ml. The limit of quantitation of each
      enantiomer was 15 ng/ml. The detection limit for each enantiomer in serum using
      UV detection at 210 nm was 7 ng/ml (S/N=2).

PMID- 9234862
TI  - Determination of hydroxyurea in plasma and peritoneal fluid by high-performance
      liquid chromatography using electrochemical detection.
AB  - A sensitive method has been developed for the determination of hydroxyurea in
      plasma and peritoneal fluid using reversed-phase high-performance liquid
      chromatography (HPLC) with electrochemical detection. Plasma or peritoneal fluid
      samples were treated with acetonitrile to precipitate proteins then injected to
      the HPLC. A C18 analytical column was used to separate hydroxyurea from
      interfering substances in the biological matrix. The mobile phase, consisting of
      0.2 M sodium perchlorate-methanol (95:5, v/v) adjusted to pH 5.0, was delivered
      isocratically at a flow-rate of 1 ml/min and hydroxyurea was detected using a
      glassy-carbon electrode operating at an applied potential of +800 mV. Hydroxyurea
      eluted with a retention time of 3 min. The cycle time for analysis is short and
      the assay precision is acceptable (C.V. plasma=1.4-3.9%. C.V. peritoneal
      fluid=2.1-9.7%). The method has been validated and is linear from 25 to 400 ng/ml
      in plasma and 5 to 30 ng/ml in peritoneal fluid. The method has been shown to be
      applicable for pharmacokinetic studies.

PMID- 9234863
TI  - Determination of a major metabolite of tipredane in rat urine by high-performance
      liquid chromatography with column switching.
AB  - An automated method, based on column-switching reversed-phase high-performance
      liquid chromatography, has been developed for the determination of a major
      metabolite of tipredane in rat urine. Samples are injected directly onto a
      cyanopropyl extraction column. The portion of eluate containing the metabolite is
      switched, via an injection loop, onto an octadecylsilane analytical column. The
      limit of quantification of the method was 25 ng/ml for a 20 microl injection
      volume of urine. The intra-assay precision (0.7-4.8%) and accuracy (94-105%), and
      the inter-assay precision (2.7-12.6%) and accuracy (94-105%), were acceptable.
      The analyte was found to be stable in rat urine when stored at room temperature
      for six days, in a freezer at or below -20 degrees C for twelve weeks, and when
      the samples were subjected to two freeze-thaw cycles. No significant interference
      was observed from tipredane and its major human metabolites, or urine
      constituents in male and female rats. The method was successfully used to analyse
      samples from a long-term toxicology study.

PMID- 9234864
TI  - Determination of the two major human metabolites of tipredane in human urine by
      high-performance liquid chromatography with column switching.
AB  - An automated method based on column-switching reversed-phase in high-performance
      liquid chromatography the heart-cutting mode has been developed for the
      simultaneous determination of the two major human metabolites of tipredane, FPL
      66365XX and FPL 66366XX, in human urine. The limit of quantification of the
      method was 25 ng/ml for both analytes from a urine injection volume of 100
      microl. The intra- and inter-assay precision and accuracy were acceptable between
      25 and 5000 ng/ml. No significant interferences were observed from either
      tipredane or a selection of its putative metabolites, or urine constituents in
      samples from male and female volunteers. Both analytes were found to be stable in
      human urine when stored at room temperature for two days, at 4 degrees C for six
      days, in a freezer at or below -20 degrees C for three weeks, and when the urine
      samples were subjected to three freeze-thaw cycles The method was unusual in that
      the initial separation was performed on a non-polar, octadecylsilane, column and
      the final separation on a more polar, trimethylsilane column. These columns were
      selected only after the investigation of a wide range of reversed-phase columns.
      The method's success was based on the greatly differing selectivities shown
      towards the two analytes by the organic modifiers, methanol and acetonitrile,
      present in the mobile phases used for the extraction and analytical stages

PMID- 9234865
TI  - Determination of simvastatin and its active metabolite in human plasma by column
      switching high-performance liquid chromatography with fluorescence detection
      after derivatization with 1-bromoacetylpyrene.
AB  - By using a fluorescent derivatization and column-switching technique, a highly
      sensitive and selective high-performance liquid chromatographic (HPLC) method has
      been developed for the determination of simvastatin (I, beta-hydroxy-delta
      lactone form) and its active hydrolyzed metabolite (II, beta,delta-dihydroxy acid
      form of I) in human plasma. A plasma sample spiked with internal standards was
      applied to a C8 solid-phase extraction column. Compounds I and II were separately
      extracted from plasma into two fractions. Compound I in one of the fractions was
      hydrolyzed to II. A fluorescent derivative was prepared by esterification of II
      with 1-bromoacetylpyrene in the presence of 18-crown-6 for both fractions. The
      pyrenacyl ester of II thus obtained was purified on a phenylboronic acid (PBA)
      solid-phase extraction column, and was measured by column-switching HPLC with
      fluorescence detection. The calibration curves for both I and II were linear in
      the concentration range of 0.1-10 ng/ml. The intra-day coefficients of variation
      were less than 11.0%, and the accuracies were between 91.7% and 117% within the
      concentration range for both analytes. The limits of quantification (LOQ) for
      both analytes were set to 0.1 ng/ml. This assay method has adequate sensitivity
      and selectivity to measure the concentrations of I and II in human plasma from
      clinical studies.

PMID- 9234866
TI  - High-performance liquid chromatographic assay for methyl-beta-cyclodextrin in
      plasma and cell lysate.
AB  - This paper describes a high-performance liquid chromatographic method with
      fluorescence detection for the analysis of methyl-beta-cyclodextrin (MEBCD) in
      plasma and cell lysate, after in situ complexation with 1-naphthol. The size
      exclusion HPLC column packed with TSK 3000 SW gel, was equilibrated with an
      eluent mixture composed of methanol and purified water (2:98, v/v) containing 10(
      4) M 1-naphthol as a fluorophore. The detection is based on fluorescence
      enhancement caused by the formation of inclusion complexes and was performed at
      290 and 360 nm for excitation and emission, respectively. The method involved a
      simple treatment of the samples with chloroform. Daunorubicin was used as
      internal standard. Limits of quantitation were 0.8 microM in plasma and 0.5
      microM in cell lysate. Detection limits of 0.5 microM (50 pmol) and 0.3 microM
      (30 pmol) were obtained for MEBCD in the two media, respectively. Linear
      detection response was obtained for concentrations ranging from 1 to 100 microM
      in plasma and cell lysate. Recovery from plasma proved to be more than 40%.
      Precision, expressed as C.V. was in the range of 4 to 11%. Accuracy ranged from
      89 to 105%.

PMID- 9234867
TI  - Simple high-performance liquid chromatographic method for the detection of
      phenylpropionylglycine in urine as a diagnostic tool in inherited medium-chain
      acyl-coenzyme A dehydrogenase deficiency.
AB  - Deficiency of medium-chain acyl-CoA dehydrogenase is a frequent and treatable
      metabolic defect, which can be diagnosed by detection of phenylpropionylglycine
      in urine after an oral load of phenylpropionic acid. We studied the determination
      of phenylpropionylglycine in urine by isocratic ion-exclusion chromatography on a
      cation-exchange column using water-sulphuric acid (pH values between 2 and 4) as
      mobile phase. Phenylpropionylglycine, phenylpropionic acid and hippuric acid
      exhibited high retention factors with only a slight decline at increasing solvent
      pH. This resulted in a good separation from interfering substances after direct
      injection of urine. We hypothesize that pi-pi interactions between the aromatic
      carbonic acids and the ion-exchange resin are responsible for the strong
      retention on the stationary phase. We conclude that, even in asymptomatic
      patients, determination of phenylpropionylglycine in urine after a
      phenylpropionic acid load by ion-exclusion chromatography is a rapid and reliable
      diagnostic tool for the detection of medium-chain acyl-CoA dehydrogenase
      deficiency.

PMID- 9234868
TI  - High-performance liquid chromatographic monitoring of intravenously administered
      diacetylmorphine and morphine and their metabolites in human plasma.
AB  - A rapid and selective reversed-phase high-performance liquid chromatographic
      assay with gradient elution and diode-array detection for diacetylmorphine,
      morphine, codeine, and their free and glucuronidated metabolites in plasma, was
      developed. After addition of ethylmorphine as internal standard the plasma
      samples were extracted using C18 ODS-2 solid-phase columns with a recovery better
      than 80%. The limit of quantitation using an injection volume of 2 microl was 25
      ng/ml for each compound. The intra- and inter-day precision was better than 5%.
      The described method cannot only be used for pharmacokinetic studies but also for
      intoxication cases to monitor a wide range of opiates.

PMID- 9234869
TI  - High-performance liquid chromatographic assay for thiopental in human plasma.
      Application to pharmacokinetic studies.
AB  - A simple assay method for the measurement of thiopental by reversed-phase high
      performance liquid chromatography (HPLC) with ultraviolet absorbance detection
      was developed. The method involved a protein precipitation with methanol.
      Carbamazepine was used as internal standard. The mobile phase was acetonitrile
      water (32:62, v/v). The elution was isocratic and the column temperature was
      ambient. Linear detection response was obtained for concentrations ranging from 1
      100 microg ml(-1). Recovery from plasma averaged 88%. Precision, expressed as
      coefficient of variation (%), was in the range of 0.2-8%. Percent recovery was at
      least 93%. Stability studies showed that plasma samples should be processed as
      promptly as possible. This method has been used in therapeutic monitoring and for
      the determination of pharmacokinetic parameters of thiopental in patients treated
      with a high dose over a long time to decrease intracranial pressure.

PMID- 9234870
TI  - Thin-layer chromatographic detection of ivermectin in cattle dung.
AB  - A qualitative method based on thin-layer chromatography (TLC) is described that
      reliably detects ivermectin as a fluorescent derivative in extracts of cattle
      dung. The limit of detection (LOD) was < or = 40 ng/g of wet dung. These
      observations were statistically documented and shown visually using digital
      imagery. Residues were detected in fresh dung deposited by animals treated 10
      days previously with a topical dose (500 microg/kg body weight) of ivermectin.

PMID- 9234871
TI  - Human experimentation.

PMID- 9234872
TI  - Accelerated healing of distal radial fractures with the use of specific, low
      intensity ultrasound. A multicenter, prospective, randomized, double-blind,
      placebo-controlled study.
AB  - A multicenter, prospective, randomized, double-blind, placebo-controlled clinical
      trial was conducted to test the efficacy of a specifically programmed, low
      intensity, non-thermal, pulsed ultrasound medical device for shortening the time
      to radiographic healing of dorsally angulated fractures (negative volar
      angulation) of the distal aspect of the radius that had been treated with
      manipulation and a cast. Sixty patients (sixty-one fractures) were enrolled in
      the study within seven days after the fracture. The patients used either an
      active ultrasound device (thirty fractures) or a placebo device (thirty-one
      fractures) daily for twenty minutes at home for ten weeks. The two types of
      devices were identical except that the placebo devices emitted no ultrasound
      energy. Clinical examination was performed and radiographs were made at one, two,
      three, four, five, six, eight, ten, twelve, and sixteen weeks after the fracture
      by each site investigator. The time to union was significantly shorter for the
      fractures that were treated with ultrasound than it was for those that were
      treated with the placebo (mean [and standard error], 61 +/- 3 days compared with
      98 +/- 5 days; p < 0.0001). Each radiographic stage of healing also was
      significantly accelerated in the group that was treated with ultrasound as
      compared with that treated with the placebo. Compared with treatment with the
      placebo, treatment with ultrasound was associated with a significantly smaller
      loss of reduction (20 +/- 6 per cent compared with 43 +/- 8 per cent; p < 0.01),
      as determined by the degree of volar angulation, as well as with a significant
      decrease in the mean time until the loss of reduction ceased (12 +/- 4 days
      compared with 25 +/- 4 days; p < 0.04). We concluded that this specific
      ultrasound signal accelerates the healing of fractures of the distal radial
      metaphysis and decreases the loss of reduction during fracture-healing.

PMID- 9234873
TI  - The patient-specific index: asking patients what they want.
AB  - The Patient-Specific Index is used to assess the outcome of total hip
      arthroplasty by evaluating the preferences of the individual patient. The purpose
      of this study was to determine the reliability, validity, and responsiveness of
      this index and to compare different methods of combining patients' ratings of the
      severity and importance of their complaints, to obtain Patient-Specific Index
      summary scores. All patients who were scheduled to have a total hip arthroplasty
      performed by one surgeon at a single institution were eligible for the study. The
      patients completed the Harris hip score form, the McMaster-Toronto Arthritis
      (MACTAR) Patient Preference Disability Questionnaire, the Short Form-36, the
      Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the
      Patient-Specific Index. With use of the Patient-Specific Index, patients rated
      the severity and importance of each complaint. These ratings were summed in four
      different ways to derive severity-importance scores. The questionnaires were
      completed twice (two weeks apart) before the total hip arthroplasty and twice
      (two weeks apart) six months after the total hip arthroplasty by a subset of the
      patients. The seventy-eight participating patients had a mean age of 62.2 years
      (range, twenty-five to eighty-seven years) at the time of the operation. Forty
      three patients (55 per cent) were men, and sixty-three (81 per cent) had
      osteoarthrosis. The inter-rater and intra-rater test-retest random-effects
      intraclass correlation coefficients of the Patient-Specific Index were 0.77 or
      greater (greater than 0.75 is considered excellent). Construct validity was shown
      by correlations of the Patient-Specific Index with other scales. The additive
      versions of the Patient-Specific Index (with a responsiveness statistic of 3.3 or
      greater and a standardized response mean of 1.6 or greater) were more responsive
      than the other scales. We concluded that the Patient-Specific Index is reliable,
      valid, and responsive. The additive versions were the most responsive and are
      recommended for future applications. Such indices need to be tested in studies of
      patients who have osteoarthrosis of the hip and other musculoskeletal diseases,
      to ensure generalizability of the results.

PMID- 9234874
TI  - Pulmonary effects of fixation of a fracture with a plate compared with
      intramedullary nailing. A canine model of fat embolism and fracture fixation.
AB  - Fat-embolism syndrome and pulmonary dysfunction may develop in multiply injured
      patients who have a fracture of a long bone. Although early fixation of a
      fracture is beneficial, intramedullary nailing may exacerbate pulmonary
      dysfunction by causing additional embolization of marrow fat. We examined the
      pulmonary effects of the timing and method of fixation of a fracture in a canine
      fat-embolism model. Fat embolism was induced in forty-one adult dogs by reaming
      the ipsilateral femur and tibia followed by pressurization of the intramedullary
      canal. The animals were divided into a control group of eight dogs that had
      induction of fat embolism alone and an experimental group of thirty-three dogs
      that had induction of fat embolism and internal fixation of a transverse fracture
      of the middle of the contralateral femoral shaft. In the control group, four dogs
      each were killed four hours and twenty-four hours after induction of fat
      embolism. In the experimental group, a femoral fracture was created and fixation
      was performed four hours after embolic showering in fifteen animals and twenty
      four hours after embolization in eighteen animals. The two experimental groups
      were subdivided according to the method of fixation of the fracture: eleven dogs
      each had application of a plate, nailing without reaming, and nailing with
      reaming. The pulmonary arterial pressure and the alveolar-arterial gradient were
      measured preoperatively, during induction of fat embolism, and as long as one
      hour after fixation of the fracture but before the animal was killed. The lungs,
      brain, and kidneys were examined for pathological and physiological evidence of
      intravascular fat. The intravascular fat persisted for twenty-four hours after
      induction of pulmonary fat embolism. Pulmonary arterial pressure remained
      elevated at four hours after the embolic showering, before creation and fixation
      of the fracture. By twenty-four hours after the induction of fat embolism,
      pulmonary arterial pressure had returned to the baseline level. Neither the
      creation nor the fixation of the fracture affected pulmonary arterial pressure.
      In the animals that had fixation of a fracture four hours after embolization,
      both nailing with reaming and nailing without reaming produced alveolar-arterial
      gradients that were higher than the baseline values, whereas fixation with a
      plate did not change the alveolar-arterial gradient significantly from the
      baseline value. In addition, the alveolar-arterial gradients in the animals that
      had nailing with reaming and nailing without reaming four hours after
      embolization were, respectively, four and 3.5 times higher than that in the
      animals that had fixation of the femur with a plate. In the animals that had
      fixation twenty-four hours after embolization, none of the methods for fixation
      affected the alveolar-arterial gradient. The amount of embolic fat in the lungs,
      brain, and kidneys was not affected by fixation of the fracture when it was
      performed at either the four-hour or the twenty-four-hour time-interval. Scores
      for pulmonary edema were increased by fixation of the fracture, but there was no
      difference among the scores associated with the three methods of fixation.
      CLINICAL RELEVANCE: The findings of the present study indicated that the amount
      of intravascular fat persisting in the lungs, kidneys, and brain twenty-four
      hours after pressurization of the intramedullary canal is not affected by the
      method of fixation of the fracture. Fixation of a fracture is associated with
      minimum evidence of acute inflammation and has no effect on pulmonary artery
      pressure. The development of pulmonary dysfunction from fat emboli depends on
      other factors, not just on the presence of fat in pulmonary vessels. It appears
      that the method of fracture fixation has little influence on the outcome of
      treatment.

PMID- 9234875
TI  - Characterization of the repair tissue after removal of the central one-third of
      the patellar ligament. An experimental study in a goat model.
AB  - The purpose of this study was to characterize the repair tissue that develops
      after removal of a portion of the patellar ligament for use as a graft. A six
      millimeter-wide strip was obtained from the central portion of the patellar
      ligament with tibial and patellar bone plugs from one knee (stifle joint) of
      eight goats. The repair tissue that formed in the defect was characterized in
      terms of its structural, material, histological, and ultrastructural properties
      twenty-one months after the operation. The contralateral patellar ligament served
      as a control. Representative specimens were taken from the proximal, middle, and
      distal portions of the repair tissue and the control tissue for histological
      study and examination with transmission electron microscopy. The six-millimeter
      long defect filled with repair tissue that increased the cross-sectional area by
      a mean of 42 per cent compared with the control values (p < 0.05). The maximum
      force to failure and the ultimate stress of the repair tissue were significantly
      decreased (by a mean of 51 and 65 per cent, respectively) compared with those of
      the controls (p < 0.001 for both). The stiffness also was reduced, by a mean of
      27 per cent, but this was not significant (p > 0.05). Magnetic resonance imaging
      of the donor site showed slightly increased signal intensity compared with the
      intensity on the control side. Histological sections from the donor site
      contained collagenous (scar) tissue that was less organized, more cellular, and
      more vascular than the control tissue. Evaluation of the ultrastructure revealed
      that the repair tissue was composed primarily of collagen fibrils with a small
      diameter (range, fifty to 100 nanometers). CLINICAL RELEVANCE: The results of the
      present study suggest that the repair tissue that develops after removal of a
      strip of the patellar ligament for use as a graft is not comparable with normal
      tissue in terms of its structural, material, histological, and ultrastructural
      properties by twenty-one months. This should be kept in mind when this repair
      tissue is considered for use as a graft for revision of a reconstruction of the
      anterior cruciate ligament.

PMID- 9234876
TI  - Long-term clinical consequences of stress-shielding after total hip arthroplasty
      without cement.
AB  - Remodeling of the femur, or so-called stress-shielding, was observed on the two
      year postoperative radiographs of forty-eight (23 per cent) of 207 hips that were
      part of a consecutive, non-selected series of 223 hips that had had a primary
      arthroplasty with use of the anatomic medullary locking hip system. Three
      patients (three hips) died within ten years after the arthroplasty, leaving forty
      four patients (forty-five hips) who had a minimum of ten years of clinical follow
      up. At the time of the latest follow-up, thirty-eight patients (86 per cent)
      reported that they had either no or mild pain related to the hip, forty-two (95
      per cent) had less pain than they had had preoperatively, and forty-one (93 per
      cent) were satisfied with the results of the arthroplasty. Two patients had a
      reoperation, but neither procedure involved the femoral component; specifically,
      one patient had a revision of a loose acetabular component and one had an
      exchange of a polyethylene liner. No femoral component was associated with
      clinical or radiographic evidence of loosening. Femoral osteolysis, confined to
      zones 1 and 7 of Gruen et al., was observed on the ten-year radiographs of four
      of the thirty-three hips for which such radiographs were available. Stress
      shielding (defined as evidence of pronounced femoral bone-remodeling on the two
      year radiographs) had not adversely affected the outcome for these four hips by
      the time of the latest follow-up. The findings regarding postoperative pain,
      function, and over-all satisfaction for the forty-four patients (forty-five hips)
      who were included in the present study were similar to those reported for our
      larger (parent) series of patients who had been managed with the anatomic
      medullary locking hip system and to those reported for a similar series of
      patients who were followed for 9.5 years after the insertion of a porous-coated
      anatomic prosthesis. In addition, the prevalence of acetabular and femoral
      osteolysis (four [12 per cent] of thirty-three hips) and that of revision of the
      femoral component (zero [0 per cent] of forty-five hips) were lower than those
      for our larger (parent) series (fifty-four [39 per cent] of 137 hips and three [1
      per cent] of 201 hips, respectively) as well as those for the series of patients
      who had been managed with the porous-coated anatomic prosthesis (thirty-five [45
      per cent] and four [5 per cent] of seventy-eight hips, respectively).

PMID- 9234877
TI  - Postmortem analysis of bone growth into porous-coated acetabular components.
AB  - Microradiography, backscattered electron microscopy, and histological analysis
      were used to conduct a quantitative postmortem study of seven consecutively
      retrieved anatomical porous replacement acetabular components that had been
      inserted during total hip arthroplasties. Screws had been used for the initial
      fixation of six components. The microradiographic analysis of all seven
      components showed that an average (and standard deviation) of 84 +/- 9 per cent
      (range, 72 to 93 per cent) of the porous coating was in direct apposition to the
      periprosthetic bone. The backscattered electron images demonstrated that an
      average of 12 +/- 6 per cent (range, 4 to 21 per cent) of the space available in
      the porous coating was occupied by ingrown bone. The amount of bone ingrowth was
      not significantly different among the three zones delineated by DeLee and
      Charnley. Uniformity of bone growth into the porous coating suggests that the
      preferential loading that occurs in the superior region did not differentially
      affect the bone ingrowth. The present study showed that consistent bone growth
      into anatomical porous replacement acetabular components can be achieved.

PMID- 9234878
TI  - Hydroxyapatite-coated total hip femoral components in patients less than fifty
      years old. Clinical and radiographic results after five to eight years of follow
      up.
AB  - One hundred and thirty-three patients (152 hips) who were an average of thirty
      nine years old (range, sixteen to forty-nine years old) received a proximally
      hydroxyapatite-coated femoral prosthesis as part of a total hip arthroplasty and
      were followed for a minimum of five years (average, 6.4 years; range, five to 8.3
      years) or until revision. The average Harris hip score was 47 points (range, 22
      to 77 points) preoperatively and 93 points (range, 49 to 100 points) at the time
      of the latest clinical evaluation. Two patients who had a well fixed femoral
      implant had activity-limiting pain in the thigh at the time of the most recent
      examination. Radiographic changes consistent with bone-remodeling (cortical
      hypertrophy and bone condensation) typically were seen around the mid-part of the
      shaft of the prosthesis. Forty-eight (32 per cent) of the 148 hips that were
      included in the radiographic analysis demonstrated a small amount of erosive
      scalloping in either zone 1 or zone 7 of Gruen et al., and intramedullary
      osteolysis was suspected in only one hip. All stems were radiographically
      osseointegrated according to a modification of the criteria described by Engh et
      al. Four stems were revised, but none of the revisions were performed because of
      mechanical failure (two stems were revised in conjunction with a revision of the
      cup because of pain; one, because of an infection; and one, after a traumatic
      femoral fracture that occurred six years postoperatively). Thus, the rates of
      aseptic and mechanical failure were both 0 per cent. The combined rate of
      failure, which included the two stems that were revised because of pain and the
      two stems that were associated with pain that limited activity, was 2.6 per cent
      (four of 152 stems). The over-all clinical results associated with hydroxyapatite
      coated femoral components were excellent in this group of young patients after
      intermediate-term follow-up. A review of serial radiographs showed mechanically
      stable implants with osseous ingrowth, evidence of stress transmission at the
      middle part of the stem, and minimum endosteal osteolysis.

PMID- 9234879
TI  - Treatment of major defects of bone with bulk allografts and stemmed components
      during total knee arthroplasty.
AB  - We reviewed the results an average of fifty months (range, twenty-four to 120
      months) after the use of thirty-five allografts in thirty patients during primary
      or revision total knee replacement. Twenty-nine femoral-head allografts, five
      distal femoral allografts, and one proximal tibial allograft were used in
      conjunction with a long-stemmed implant to reconstruct large osseous defects. The
      patients were evaluated clinically, radiographically, and subjectively (with use
      of a questionnaire). Twenty-six (87 per cent) of the thirty patients had a good
      or excellent clinical result, and no revisions were necessary. As none of the
      patients had collapse of the graft, subsidence of the implant, or revision, we
      believe that the outcome of treatment with a femoral-head allograft, particularly
      in association with a component inserted with cement, is excellent. Four non
      porous-coated components were placed without cement on structural allografts.
      Radiographically, three of those components subsided, but none of the three
      needed revision and two were associated with a good clinical result. Our current
      practice is to cement components in all arthroplasties involving grafting. Our
      findings suggest that the use of a stemmed component reduces the stress on the
      allograft, host bone, and fixation interface. In addition, such a component
      contributes to the longevity of a total knee replacement associated with a bone
      graft. Additional studies with long-term follow-up are necessary to confirm this
      outcome.

PMID- 9234880
TI  - Radiographic evaluation of penetration by the femoral head into the polyethylene
      liner over time.
AB  - We examined the pattern of temporal penetration by thirty-two-millimeter-diameter
      femoral heads into polyethylene liners in a group of 105 hips (103 patients) in
      which an Arthropor metal-backed cup had been implanted. Each patient was
      evaluated radiographically and clinically at a minimum of four different
      postoperative intervals. The initial evaluation was performed a mean of 2.9 weeks
      (range, one to fifteen weeks) postoperatively, and the latest evaluation was
      performed a mean of 7.9 years (range, five to ten years) postoperatively. Two
      dimensional wear - that is, penetration by the femoral head into the ultra-high
      molecular weight polyethylene liner - was determined from anteroposterior
      radiographs of the pelvis with a computer analysis system that calculated the
      change in the position of the center of the head relative to the center of the
      cup. Three new findings are reported. First, there was a large difference (mean,
      1.1 millimeters) between the center of the head and that of the cup as measured
      on the initial postoperative radiographs. This difference underscores the need
      for researchers to consider the initial displacement of the head when measuring
      and reporting polyethylene wear. Second, although there was wide variation in
      responses among individuals, temporal examination of the data revealed a trend
      toward a decreasing rate of penetration with time. Moreover, the rate of
      penetration appeared to reach a steady-state value after the sixth postoperative
      year and remained nearly constant until the ninth postoperative year. Third, by
      comparing the subsets of patients who had the greatest and the least initial
      penetration by the head, we found that penetration behavior, although remarkably
      different between the groups in the first three years postoperatively, became
      similar with time. CLINICAL RELEVANCE: When making decisions regarding individual
      patients or hip systems that demonstrate penetration by the femoral head into the
      polyethylene liner, clinicians should consider the patterns of penetration over
      time. Measurements of the amount and rate of penetration that are based solely on
      the most recent radiograph do not represent the full clinical picture. We
      advocate more frequent radiographic follow-up and, when available, analysis of
      serial radiographs for patients who have excessive penetration by the femoral
      head into the acetabular liner.

PMID- 9234881
TI  - Abnormalities in the bone marrow of the iliac crest in patients who have
      osteonecrosis secondary to corticosteroid therapy or alcohol abuse.
AB  - The bone-marrow activity in the iliac crest of eleven patients who had idiopathic
      osteonecrosis of the hip and thirty patients who had osteonecrosis of the hip
      that was related to corticosteroid therapy (fourteen patients) or to alcohol
      abuse (sixteen patients) was compared with that in two groups of control subjects
      who did not have osteonecrosis (thirty-three healthy bone-marrow donors and
      thirty-four patients who had been managed with bone-marrow grafting for a non
      union). Cultures of granulocyte-macrophage progenitor cells and fibroblast colony
      forming units were performed to assess the activity of hematopoietic stem cells
      and stromal cells. The activity of stem cells in both the hematopoietic and the
      stromal compartment of the bone marrow was decreased in the patients who were
      receiving corticosteroids or who abused alcohol, as compared with that in the two
      groups of control subjects. The patients who had idiopathic osteonecrosis also
      had a decrease in bone-marrow activity compared with the control subjects.
      CLINICAL RELEVANCE: Our findings suggest that patients who are receiving
      corticosteroid therapy or who abuse alcohol have decreased activity of bone
      marrow cells. Whether this decrease is related to the osteonecrosis could not be
      determined, as our study did not include control subjects who had a history of
      alcohol abuse or who were receiving corticosteroids but did not have
      osteonecrosis. However, it is possible that the reduced bone-marrow activity was
      related to the osteonecrosis, as patients who had idiopathic osteonecrosis also
      had decreased bone-marrow activity. The study of pathological alterations in the
      bone marrow outside the necrotic zone may provide important insights into the
      pathophysiology of osteonecrosis.

PMID- 9234882
TI  - Steroid-induced adipogenesis in a pluripotential cell line from bone marrow.
AB  - We studied the effect of steroids on the differentiation of a pluripotential
      mesenchymal cell with use of a cell line (D1) from mouse bone-marrow stroma. The
      cells were treated with increasing (10[-9], 10(-8), and 10(-7)-molar)
      concentrations of dexamethasone for increasing durations ranging from forty-eight
      hours to twenty-one days. The appearance of triglyceride vesicles in the cells
      indicated that this treatment had induced the differentiation of the cell into
      adipocytes. The number of cells that contained the triglyceride vesicles and the
      expression of a fat-cell-specific gene, 422(aP2), increased with longer durations
      of exposure to dexamethasone and with higher concentrations of the steroid.
      Treatment with dexamethasone also diminished the expression of alpha1 type-I
      collagen mRNA and osteocalcin mRNA. The data indicate that dexamethasone
      stimulates the differentiation of cells in bone-marrow stroma into adipocytes as
      well as the accumulation of fat in the marrow at the expense of expression of
      type-I collagen and osteocalcin mRNA, thereby suppressing differentiation into
      osteoblasts. CLINICAL RELEVANCE: Steroid-induced adipogenesis by bone progenitor
      cells in marrow may influence the development of osteonecrosis. It is therefore
      important to consider the investigation of a treatment, such as the inhibition of
      the metabolism and accumulation of fat in marrow, that can prevent the onset of
      osteonecrosis.

PMID- 9234884
TI  - Cervical myelopathy caused by bilateral fibrosis of the dorsal root ganglion in a
      patient who had rheumatoid arthritis. A case report.

PMID- 9234885
TI  - Use of an osteocutaneous plantar free flap for salvage of a below-the-knee
      amputation in a child. A case report.

PMID- 9234883
TI  - Strength of fixation with transosseous sutures in rotator cuff repair.
AB  - The effect of various configurations of placement of transosseous sutures on the
      immediate strength of fixation was studied in forty-five fresh-frozen humeri from
      cadavera of older individuals (mean age at the time of death, sixty-three years).
      The ultimate strength (the strength to failure) was significantly greater (p <
      0.05) when the sutures were placed at sites more distal to the tip of the greater
      tuberosity or when the sutures were tied over a wider bone bridge. Cortical
      augmentation with use of a plastic button through which the transosseous sutures
      were tied increased the ultimate strength approximately 1.9-fold. The increase in
      the ultimate strength of the transosseous repair corresponded significantly with
      the increasing mean thickness of the cortical bone as the sutures were placed
      more distally along the lateral aspect of the humerus. We concluded that the
      strength of the fixation of a rotator cuff repair can be increased by placing the
      transosseous sutures at least ten millimeters distal to the tip of the greater
      tuberosity and by tying them over a bone bridge that is at least ten millimeters
      wide. When bone is very osteoporotic, cortical augmentation with a readily
      available plastic button strengthens the repair.

PMID- 9234886
TI  - Fracture of the scapula with intrathoracic penetration. A case report.

PMID- 9234887
TI  - Familial heterozygous protein-S deficiency in a patient who had multifocal
      osteonecrosis. A case report.

PMID- 9234888
TI  - Bursal osteochondromatosis overlying an osteochondroma of a rib. A case report.

PMID- 9234889
TI  - The conduct of orthopaedic clinical trials.

PMID- 9234890
TI  - Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg
      Perthes disease.

PMID- 9234891
TI  - Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg
      Perthes disease.

PMID- 9234892
TI  - The development of two fluorimetric assays for the determination of pyroglutamyl
      aminopeptidase type-II activity.
AB  - Two fluorimetric assays for the determination of pyroglutamyl aminopeptidase type
      II activity have been developed. The assays are based on hydrolysis of the
      quenched-fluorimetric substrate <Glu-His-Pro-7-amino-4-methylcoumarin. Following
      the removal of the N-terminal <Glu by pyroglutamyl aminopeptidase type-II,
      liberation of 7-amino-4-methylcoumarin from the metabolite His-Pro-7-amino-4
      methylcoumarin is catalyzed by one of two methods: (i) the addition of partially
      purified bovine serum dipeptidyl aminopeptidase type-IV or (ii) by incubating the
      reaction mixture for up to 2 h at 80 degrees C, thus promoting the nonenzymatic
      cyclization of His-Pro-7-amino-4-methylcoumarin to cyclo His-Pro and free 7-amino
      4-methylcoumarin. Pyroglutamyl aminopeptidase type-II from bovine brain is used
      to establish appropriate assay conditions. These fluorimetric assays offer
      expeditious alternatives to the existing radiolabeled thyrotropin-releasing
      hormone assays for the determination of PAPII activity.

PMID- 9234893
TI  - Identification of the colored guaiacol oxidation product produced by peroxidases.
AB  - Oxidation of guaiacol by peroxidases in the presence of H2O2 is the basis for a
      widely used colorimetric assay. However, the nature of the assay product, which
      has an absorption maximum around 470 nm, had not been determined. In the present
      study, we combined HPLC with a rapid scanning uv-visible detector and observed a
      single product with a spectrum identical to the assay product from the reaction
      catalyzed by lactoperoxidase. Analysis of the reaction product using on-line HPLC
      with atmospheric pressure chemical ionization detection (LC-APCI/MS) yielded a
      mass spectrum consistent with 3,3 '-dimethoxy-4,4'-biphenylquinone. A minor
      reaction product was observed with mass spectrum consistent with 3,3'-dimethoxy
      4,4'-dihydroxybiphenyl. The presence of a catechol impurity in guaiacol was
      previously shown to yield an additional product from peroxidase-mediated
      oxidation based on its visible absorption (Taurog et al., 1992 Anal. Biochem.
      205, 271-277). When such an incubation mixture was analyzed using LC-APCI/MS, a
      product with mass spectrum consistent with 3-methoxy-2',3',4-trihydroxybiphenyl
      was observed. Identification of such a heterodimeric product supports the
      previously proposed mechanism for catechol interference in the guaiacol assay as
      well as the radical nature of peroxidase-catalyzed oxidation of phenols.

PMID- 9234894
TI  - Characterization of neutral oligosaccharide-alditols from Xenopus laevis egg
      jelly coats by matrix-assisted laser desorption Fourier transform mass
      spectrometry.
AB  - Neutral oligosaccharides were released by alkaline sodium borohydride reduction
      of the jelly coating from the South African clawed toad, Xenopus laevis. The
      oligosaccharides were isolated by HPLC and analyzed by matrix-assisted laser
      desorption ionization (MALDI)-Fourier transform mass spectrometry (FTMS). The
      mass spectrometry analysis allowed confirmation of 12 structures first proposed
      by Strecker et al. using nuclear magnetic resonance. In addition, seven new
      oligosaccharides with weak abundances were found and characterized by mass
      spectrometry. A method for discriminating metastable fragments from
      quasimolecular ions is described. It involves doping the sample with cesium
      chloride. Cesium-coordinated oligosaccharides do not fragment as readily as those
      coordinated to sodium. Tandem MS experiments are performed on an unknown
      oligosaccharide illustrating the potential of MALDI-collision-induced
      dissociation-FTMS.

PMID- 9234895
TI  - Continuous spectrophotometric assay of peptide deformylase.
AB  - A continuous assay for peptide deformylase has been developed using a formylated
      dipeptide, formyl-Met-Leu-p-nitroanilide, as substrate. Removal of the formyl
      group by a peptide deformylase renders the dipeptide product, which contains a
      free NH2 terminus, a substrate for an aminopeptidase from Aeromonas proteolytica.
      Sequential hydrolysis of the dipeptide by the aminopeptidase releases a p
      nitroaniline, which is monitored spectrophotometrically at 405 nm. This assay was
      applied to determine the pH optimum and the catalytic activity of a peptide
      deformylase from Escherichia coli. The E. coli enzyme is most active near neutral
      pH (pH 7.0) and displays Michaelis-Menten kinetics toward the formylated
      dipeptide, with K(M) = 20.3 +/- 1.3 microM, k(cat) = 38 +/- 2 s(-1), and
      k(cat)/K(M) = 1.9 x 10(6) M(-1) s(-1). It also exhibits an acylase activity,
      capable of deacylating N-acetyl-Met-Leu-p-nitroanilide and N-trifluoroacetyl-Met
      Leu-p-nitroanilide, albeit at drastically reduced rates. These results
      demonstrate that the current assay is a convenient, rapid, and sensitive method
      for kinetic studies of peptide deformylase. The strategy employed in this work
      should also be generally applicable to the characterization of other acylases.

PMID- 9234896
TI  - A colorimetric estimation of polyethyleneglycol-conjugated phospholipid in
      stealth liposomes.
AB  - The paper describes a colorimetric method for estimation of polyethyleneglycol
      (PEG)-conjugated phospholipid in either form, free or bound to liposomes. It
      provides a rapid, highly reproducible, and sensitive tool to detect PEG-coupled
      phospholipid in amounts as low as 1 microg giving a linear response over a range
      of 1-100 microg. The method makes use of the biphasic system comprising aqueous
      ammonium ferrithiocyanate and chloroform, developed by Stewart for estimation of
      phospholipids. The same system was also applied for quantitation of PEG in PEG
      protein conjugates in a recent report. The samples were digested with
      phospholipase-C, prior to analysis, in order to eliminate the contributions from
      liposomal phospholipids other than the PEG-conjugated phospholipid. The technique
      can give valuable information regarding the retention of PEG coating on the
      surface of the vesicles when employed in combination with markers for the aqueous
      compartment. In addition, it does not suffer from interference by proteins. This
      makes it particularly suitable for monitoring the pharmacokinetics of stealth
      liposomes, using PEG-phospholipid as a lipid probe. Since it does not involve
      handling hazardous radioisotopes, the suggested technique could even be utilized
      in clinical trials.

PMID- 9234898
TI  - A generic method for the production of cell lines expressing high levels of 7
      transmembrane receptors.
AB  - G-protein-coupled or 7-transmembrane receptors (7TMRs) are often studied after
      heterologous expression in mammalian cells such as COS-7, CHO-K1, or HEK-293s. In
      this paper, we describe the development of a rapid and generic method for
      producing stable Chinese hamster ovary cell lines expressing high levels of
      recombinant 7TMRs by N-terminal tagging these proteins with the hemagglutinin
      (HA) sequence. To illustrate the broad applicability of this technique, we have
      presented data from cell lines expressing a glycoprotein hormone receptor for
      follicle-stimulating hormone (FSHR), CXC- (CXCR-2), and CC-chemokine (CCR-1)
      receptors and peptide receptors from the somatostatin (SSTR1, 2, 5) and
      neuropeptide Y (NPY-Y2, -Y4 Rs) families. Typically, cell lines with a receptor
      density of 1 to 15 pmol/mg protein are produced with this method. The presence of
      the HA tag does not adversely affect the binding or functional activity of the
      receptors.

PMID- 9234897
TI  - Inhibition of acyl-CoA oxidase by phenol and its implication in measurement of
      the enzyme activity via the peroxidase-coupled assay system.
AB  - Yeast (Candida tropicalis) acyl-CoA oxidase catalyzes the oxidation of a variety
      of acyl-CoA substrates to their corresponding alpha-beta enoyl-CoA products, with
      concomitant reduction of the buffer-dissolved O2 to H2O2. By utilizing
      indolepropionyl-CoA as a chromogenic substrate, we could measure the enzyme
      activity either directly by monitoring formation of the reaction product
      indoleacryloyl-CoA (lambda(max) = 367 nm) or indirectly by measuring the
      formation of H2O2 via the oxidative-coupled assay system, involving 4
      aminoantipyrine, phenol, and horseradish peroxidase. We compared the rates of the
      enzyme catalysis by the above two methods. The experimental data revealed that
      the rate measured via the direct method was about twofold higher than that
      measured by the coupled-assay system. The above difference was found to be due to
      the inhibition of the enzyme by phenol, one of the reagents of the coupled assay
      system. The inhibitory role of phenol is not unique for indolepropionyl-CoA as
      substrate, but is also evident with aliphatic acyl-CoA substrates of varied chain
      lengths. Since the magnitude of inhibition is dependent on the nature of the acyl
      CoA substrate, it is suggested that the coupled-reaction conditions must be
      carefully standardized with individual substrates. Some tips on standardizing the
      reaction conditions for quantitative measurement of the acyl-CoA oxidase
      catalyzed reaction are offered.

PMID- 9234899
TI  - Micropreparative high resolution purification of proteins by a combination of
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing,
      and membrane blotting.
AB  - We report a simple, economical, and efficient protocol for protein purification
      from cells. First, proteins of cell lysates were separated by standard sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotted
      to protein-blotting membrane. The blots were stained with Coomassie blue or
      developed by immunoblotting to visualize specific proteins. The bands
      corresponding to those visible by immunoblotting were excised from the dye
      stained blots and subjected to isoelectric focusing. The focused gel was stained
      with Coomassie blue. Finally, the stained bands were excised and subjected to
      another SDS-PAGE separation and electrotransferred back to protein-blotting
      membrane. At this stage, the purified proteins were suitable for microsequencing.
      We have tested the feasibility of this novel technique by purifying proteins with
      molecular weights ranging from 19 to 100 kDa from a lysate of Sarcocystis
      neurona, the etiologic agent of equine protozoal myeloencephalitis. The purity of
      proteins was demonstrated by reverse-phase high-performance liquid
      chromatography. Partial sequences of these purified proteins were obtained by N
      terminal or digestive sequencing.

PMID- 9234900
TI  - Simultaneous detection of ubiquinol and ubiquinone in human plasma as a marker of
      oxidative stress.
AB  - A method is described for the simultaneous detection of ubiquinol-10 and
      ubiquinone-10 in human plasma. In this procedure, heparinized human plasma was
      mixed with 5 vol of methanol and 10 vol of hexane. After vigorous shaking and
      centrifugation, an aliquot of the hexane phase (5 microl) was injected
      immediately and directly onto a reversed-phase HPLC to minimize the oxidation of
      ubiquinol to ubiquinone. A post-separation, on-line reduction column converts
      ubiquinone to ubiquinol which is quantified by electrochemical detection. The
      detection limit of plasma ubiquinol-10 and ubiquinone-10 is about 4 nM with
      excellent reproducibilities. Tocopherols, lycopene, and beta-carotene are also
      detectable in this method. In addition, free cholesterol, and cholesteryl esters
      can be quantified by their absorption at 210 nm. Using this method we have
      determined the ratio of ubiquinol to ubiquinone is about 95/5 in human plasma
      from healthy donors. We suggest that this method will be useful since the ratio
      of ubiquinol to ubiquinone has been suggested as a good marker of oxidative
      stress.

PMID- 9234901
TI  - Electrochemical assay of proteinase inhibitors using polycation-sensitive
      membrane electrode detection.
AB  - A simple and sensitive electrochemical method suitable for real time detection of
      trypsin-like proteinase inhibitors is described. The method is based on utilizing
      a protamine (a polycationic substrate for trypsin-like proteinases)-sensitive
      membrane electrode to monitor, potentiometrically, the initial rate of protamine
      decomposition upon the addition of a proteinase-antiproteinase test solution. In
      the presence of proteinase inhibitors, the initial rate of change in
      electromotive force is dependent on the concentration of proteinase inhibitor in
      the sample solution. The feasibility of this new assay method is demonstrated by
      detecting four inhibitors of trypsin-like proteinases: alpha1-antiproteinase
      inhibitor, alpha2-macroglobulin, aprotinin, and soybean inhibitor, using trypsin
      as the indicator proteinase. The efficacy of inhibition by each species, as
      expressed by I50 values (concentration of the inhibitor that induces 50% of the
      maximum proteinase inhibition), is shown to correlate well with literature values
      for the association constant of the proteinase-antiproteinase complex (k[assoc]).
      The proposed electrochemical assay for aprotinin is examined further using
      trypsin, plasmin, and kallikrein as the proteinase indicator reagents. It is
      found that the trypsin-aprotinin system offers the highest sensitivity and lowest
      detection limit for aprotinin detection. Application of the proposed method for
      measuring aprotinin in pretreated plasma samples is also reported.

PMID- 9234902
TI  - Sequencing of N-linked oligosaccharides directly from protein gels: in-gel
      deglycosylation followed by matrix-assisted laser desorption/ionization mass
      spectrometry and normal-phase high-performance liquid chromatography.
AB  - A generally applicable, rapid, and sensitive method for profiling and sequencing
      of glycoprotein-associated N-linked oligosaccharides from protein gels was
      developed. The method employed sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) for protein separation and purification and in-gel
      deglycosylation using PNGase F for glycan release. Profiles of the neutral
      glycans from bovine ribonuclease B, chicken ovalbumin, and human immunoglobulin G
      (IgG), as well as sialic acid-containing sugars (following esterification of the
      acidic groups) of bovine fetuin and bovine alpha1-acid glycoprotein, were
      obtained by matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) and by normal-phase high-performance liquid chromatography following
      fluorescent labeling. Oligosaccharides were sequenced using specific
      exoglycosidases, and digestion products were analyzed by MALDI MS. Between 50 and
      100 pmol (1.5 to 15 microg) of glycoprotein applied to the gel was sufficient to
      characterize its oligosaccharide contents. The identity of all glycoproteins
      investigated could be confirmed after deglycosylation by in-gel trypsin treatment
      followed by MALDI MS mass mapping and matching the measured molecular weights to
      a sequence database. The technique was used for the characterization of the
      glycan moieties of human immunodeficiency virus recombinant gp120 (Chinese
      hamster ovary cells) and to monitor changes in the glycosylation of this
      glycoprotein when produced in the presence of a glucosidase I inhibitor.
      Furthermore, since heavy and light chains of IgG became separated by SDS-PAGE, it
      could be established that most glycans were associated with the heavy chains.

PMID- 9234903
TI  - Lifetime-based sensing of glucose using energy transfer with a long lifetime
      donor.
AB  - We describe an optical assay for glucose based on the luminescence decay time of
      a long lifetime metal-ligand complex. Concanavalin A was covalently labeled with
      Ruthenium metal-ligand complex (RuCon A) which served as the donor. The acceptor
      was malachite green which was covalently linked to insulin. The malachite green
      insulin was also covalently labeled with maltose (MIMG) to provide binding
      affinity to RuCon A. Binding of RuCon A to MIMG resulted in a decreased intensity
      and decay time of RuCon A. Glucose was detected by competitive displacement of
      MIMG from RuCon A, resulting in increased intensity and decay time. This glucose
      assay has several favorable features. The long lifetime of RuCon A allows phase
      modulation decay time measurements using an amplitude-modulated bluelight
      emitting diode as the light source. Reversibility of the assay can be controlled
      by the extent of sugar labeling of the insulin. Finally, the glucose-sensitive
      range can be adjusted by selection of the sugar structure and extent of labeling
      of the insulin.

PMID- 9234904
TI  - A phospholipase A2 kinetic and binding assay using phospholipid-coated
      hydrophobic beads.
AB  - A novel kinetic and membrane-binding assay for phospholipase A2 (PLA2) has been
      developed utilizing phospholipid-coated hydrophobic styrene-divinylbenzene beads
      (5.2 +/- 0.3 microm diameter). Phospholipids formed a stable monolayer film on
      styrene-divinylbenzene beads with average surface packing density of (1.3 +/-
      0.2) x 10(-2) molecule/A2. Secretory PLA2 readily hydrolyzed 1-palmitoyl-2-[3H]
      oleoyl-sn-glycero-3-phosphoglycerol coated on styrene-divinylbenzene beads which
      could be easily monitored by measuring the radioactivity of fatty acid released
      to solution in the presence of bovine serum albumin. For human cytosolic PLA2
      with high specificity for sn-2 arachidonyl group, styrene-divinylbenzene beads
      coated with 1-stearoyl-2-[14C]-arachidonyl-sn-glycero-3-phosphocholine and
      dioleoylglycerol (7:3, mol/mol) were used as substrate. PLA2 activity was
      linearly proportional to the enzyme concentration in the range from 1 to 150 nM
      for human class II secretory PLA2 and from 1 to 20 nM for cytosolic PLA2; the
      specific activity was 1.6 and 1.7 micromol/min/mg, respectively. Finally, styrene
      divinylbenzene beads coated with polymerized 1,2-bis[12-(lipoyloxy) dodecanoyl]
      sn-glycero-3-phosphoglycerol were used to measure the membrane binding affinity
      of PLA2, which in conjunction with kinetic data provides important insights into
      how PLA2 interacts with membranes.

PMID- 9234905
TI  - Miniprep DNA isolation for automated sequencing of multiple samples.

PMID- 9234906
TI  - Synthesis and use of a novel biotinylated probe for the chemiluminescent
      detection of proteins that bind 15-hydroxyeicosatetraenoic acid.

PMID- 9234907
TI  - Electrochemical analysis of DNA amplified by the polymerase chain reaction with a
      ferrocenylated oligonucleotide.

PMID- 9234908
TI  - Inadvertent concentrating of EDTA by ion exchange chromatography: avoiding
      artifacts that can interfere with protein purification.

PMID- 9234909
TI  - DNA isolation from single or half seeds suitable for random amplified polymorphic
      DNA analyses.

PMID- 9234910
TI  - Magnetic bead purification of specific transcription factors using mutant
      competitor oligonucleotides.

PMID- 9234911
TI  - Hereditary ovarian cancer: a different disease?

PMID- 9234912
TI  - Age at onset of ovarian cancer in women with a strong family history of ovarian
      cancer.
AB  - OBJECTIVE: To determine whether women with a strong family history of ovarian
      cancer develop ovarian cancer at a younger age than the general population, and
      to determine if the age at onset of ovarian cancer in families with multiple
      cases of ovarian cancer is progressively younger with successive generations.
      METHODS: Using a large voluntary familial ovarian cancer registry, 90 probands
      were identified whose grandmothers had developed ovarian cancer and for whom the
      age at onset was known. The distribution of age at onset of ovarian cancer in the
      grandmothers was compared to the expected distribution based on data from the
      Surveillance Epidemiology End Results (SEER) project. In addition, 131 families
      were identified for whom complete pedigrees were available and in whom 3 or more
      family members had developed ovarian cancer. Ovarian cancer-free survival curves
      were constructed for each aggregate generation (using the probands as the
      reference generation) utilizing the Kaplan-Meier method. RESULTS: Among the 90
      grandmothers, 18 from families with 3 or more cases of ovarian cancer had a
      distribution of age of onset that was younger than expected (P = 0.02). However,
      the distribution of age at onset among the 72 grandmothers from families with
      only 2 cases of ovarian cancer was not significantly different from that expected
      based on the SEER data (P = 0.18). Among the 131 families with 3 or more cases of
      ovarian cancer, the probands' daughters developed ovarian cancer at a younger age
      than the probands (P = 0.018), probands developed ovarian cancer at a younger age
      than their mothers (P = 0.0008), and the probands' mothers developed ovarian
      cancer at a younger age than the probands' grandmothers (P = 0.0038).
      CONCLUSIONS: Ovarian cancer patients from families with 3 or more cases of
      ovarian cancer tend to develop their cancer at a younger than expected age. This
      is consistent with the phenomenon known as anticipation.

PMID- 9234913
TI  - Comparison of Fourier-transform infrared spectroscopic screening of exfoliated
      cervical cells with standard Papanicolaou screening.
AB  - To compare Fourier-transform infrared (FTIR) spectroscopy in screening cervical
      cytology and standard Papanicolaou (Pap) screening with colposcopic directed
      biopsy as a "gold standard," we prospectively gathered FTIR samples and Pap
      smears of all patients attending our program's colposcopy clinics, from February
      to October 1995. We recorded demographic data for each patient including
      colposcopy, cytology, treatment follow-up, and histology. Using the
      colposcopically directed biopsy as the gold standard, exfoliated cervical cells
      from 301 patients were collected to compare cytology and FTIR spectroscopy. Based
      on previously established criteria, we provided distinctive definitions of both
      negative/positive FTIR, cytology, and histology. Results of 301 cases showed 196
      positive and 105 negative cytologies. The sensitivity, specificity, false
      negative rate, and false-positive rate for the Pap test were 86.6, 90.5, 13.4,
      and 9.5%, respectively. However, FTIR results versus histology showed 215
      positive and 86 negative with a sensitivity of 98.6% and specificity of 98.8%.
      False-negative and false-positive rates were 1.4 and 1.2%, respectively. In the
      12 cervical cancers there were no false-negative FTIR results but 3 false
      negative Pap smears. The positive and negative predictive values for FTIR were
      99.5 and 96.5% while the Pap values were 95.9 and 72.3%. Compared to standard Pap
      smears, FTIR has a better false-negative rate and negative predictive value in
      this preliminary study. Further work, to establish the range of each of the
      spectral criteria for different grades of dysplasia and that among various
      infectious effects, needs to be conducted before applying this research tool to a
      population-based study.

PMID- 9234914
TI  - Perineal template interstitial brachytherapy salvage for recurrent endometrial
      adenocarcinoma metastatic to the vagina.
AB  - PURPOSE: To evaluate the use of interstitial brachytherapy salvage of recurrent
      endometrial adenocarcinoma metastatic to the vagina. METHODS: From September 1989
      to February 1995, 15 patients with locally recurrent endometrial adenocarcinoma
      were treated with perineal template interstitial irradiation with low-dose-rate
      brachytherapy 192Ir/137Cs. Five of the 7 previously unirradiated patients
      received pelvic external beam radiation therapy (EBRT) of 45-50 Gy, with standard
      fractionation followed by an interstitial brachytherapy boost dose of 30 Gy
      (range 25 to 35 Gy). The other 2 patients received only brachytherapy of 40 Gy
      (palliative) and 50 Gy. Eight previously irradiated patients received only
      brachytherapy of 50 to 55 Gy. RESULTS: After a median follow-up of 47 months
      (range 14-81), the actuarial local control rate was 66.6%. The local control rate
      for patients treated with interstitial irradiation only was 64.3% and the local
      control rate for patients treated with interstitial irradiation + EBRT was 100%.
      Distant metastases occurred in 30.7% of the patients. Actuarial overall and
      disease-specific 5-year survival were 42.3 and 67.5%, respectively. Toxicity has
      been minimal, with 6 patients complaining of vaginal/rectal (RTOG) grade 1-3
      complications (5 patients grade 1-2, 1 patient grade 3). CONCLUSIONS: These
      results suggest that perineal template interstitial irradiation (if possible with
      supplementary EBRT) is an effective alternative to radical or exenterative pelvic
      surgery for locally recurrent endometrial cancer. Excellent survival and local
      control rates can be achieved with low morbidity, especially if EBRT is added.

PMID- 9234915
TI  - Hexamethylmelamine as a single second-line agent in ovarian cancer: follow-up
      report and review of the literature.
AB  - From December 1982 to December 1986, 52 patients with recurrent ovarian cancer
      were treated with single-agent HMM. Chemotherapy was given for a period of 1 year
      unless progression of disease or toxicity was noted. Survival was determined from
      the time of diagnosis to the date of death or September 30, 1992. The regimen was
      well tolerated with only one case of severe gastrointestinal toxicity. Nine
      patients were found to be clinically free of disease following completion of HMM
      treatment; they had initially responded to cisplatin-based therapy (i.e.,
      potentially cisplatin-sensitive) and subsequently recurred. Four were found to
      have gross disease at the time of reassessment laparotomy. Three of these 9
      patients are alive 81-92 months since diagnosis, having maintained disease-free
      intervals of up to 6 years. The median survival for the 9 patients without
      evidence of disease at the end of therapy was 75 months versus 9 months for the
      nonresponders. No patient who had progressive disease on first-line cisplatin
      based combination chemotherapy (i.e., primary cisplatin-resistant) responded to
      second-line single-agent oral hexamethylmelamine. With a follow-up close to 10
      years, our data show that hexamethylmelamine, with reasonable toxicity, can
      provide an extended, disease-free interval to a selected group of patients.

PMID- 9234916
TI  - Serum evaluation of interleukin 6 in ovarian cancer patients.
AB  - BACKGROUND: Cytokines are intercellular hormones, believed to play a functional
      role in the natural history of various malignant diseases. In vitro and in vivo
      studies have indicated that interleukin 6 (IL-6) may provide autocrine and
      paracrine growth stimulation in ovarian cancer cells. METHODS: In the present
      study we measured IL-6 in the serum of 73 patients with FIGO stage I to IV
      ovarian cancer. Enzyme-linked immunosorbent assay (ELISA) was used to determine
      IL-6 serum levels. Results were correlated to clinical data. Serum levels of IL-6
      were additionally evaluated in a panel of 50 normal controls. RESULTS: Median
      serum levels of IL-6 in patients with ovarian cancer and normal controls were
      55.6 (minimum 0, maximum 2869.0) pg/ml and 0.5 (minimum 0, maximum 2.14) pg/ml,
      respectively (Mann-Whitney U test, P = 0.0001). When serum levels of IL-6, taken
      prior to therapy, were grouped by FIGO stage, lymph node involvement, and grading
      of tumor cells, we found a statistically significant correlation with FIGO stage
      (Mann-Whitney U test, P = 0.04). Lymph node involvement and grading of tumor
      cells were not correlated with IL-6 levels. Elevated IL-6 serum levels prior to
      therapy were significantly correlated with poorer disease-free (log-rank test, P
      = 0.003) and overall survival (log-rank test, P = 0.01). CONCLUSION: Elevated IL
      6 serum levels prior to therapy are correlated with a poor relapse-free and
      overall survival in ovarian cancer patients.

PMID- 9234917
TI  - Stage IB and IIA cervical cancer with negative lymph nodes: the role of adjuvant
      radiotherapy after radical hysterectomy.
AB  - The records of 171 patients with lymph node-negative stage IB and IIA cervical
      cancer primarily treated with radical hysterectomy and pelvic lymphadenectomy
      from 1974 to 1992 were retrospectively reviewed to identify poor prognostic
      factors and evaluate the role of adjuvant pelvic radiotherapy. One hundred
      sixteen patients (68%) were treated with radical hysterectomy alone (RH) and 55
      patients (32%) received adjuvant radiotherapy (RH + RT). Factors predictive of
      recurrence for the entire group of patients included lymph-vascular space
      invasion (LVSI) (P = 0.003) and grade 3 histology (P = 0.04). Patients receiving
      RH + RT were older and more likely to have outer third cervical wall invasion,
      LVSI, positive margins, > or =2 cm pathologic tumor size, and >4 cm clinical
      tumor size (all P < 0.05). Overall, 28 patients (16%) developed recurrent disease
      with no difference between RH and RH + RT groups. After controlling for
      confounding variables, patients with LVSI who received RH + RT were less likely
      to develop disease recurrence than patients receiving RH alone (P = 0.04). LVSI
      is an important prognostic variable in lymph node-negative stage IB and IIA
      cervical cancer. Although adjuvant pelvic radiotherapy may decrease the risk of
      recurrence in patients with LVSI, the majority of patients with negative lymph
      nodes may be treated with radical surgery alone.

PMID- 9234918
TI  - Loss of heterozygosity in human ovarian cancer on chromosome 19q.
AB  - Abnormalities in the function of oncogenes and tumor suppressor genes have been
      associated with many human malignancies. The recognition of sites of loss of
      heterozygosity (LOH) has led to the identification of such genes. We previously
      reported that abnormalities of mRNA expression of ERCC1 and ERCC2 may be
      characteristic of epithelial ovarian carcinoma and brain tumors. This led to an
      investigation of chromosome 19q13.2-q13.4 which contains these DNA repair genes.
      A 7-Mb region was analyzed using six microsatellite repeats. Loss of
      heterozygosity has been identified in 53% (8/15) of cases at marker D19S246 which
      lies in a 2-Mb segment between HRC and KLK1. The genetic material both
      centromeric and telomeric to the region of loss was conserved. This area is
      telomeric to three DNA repair genes where LIG1 is 1-Mb centromeric and ERCC1 and
      ERCC2 are 3.5- and 4.0-Mb centromeric, respectively. These findings represent the
      first report of a biologically significant rate of LOH on chromosome 19q13.2
      q13.4 in human ovarian carcinoma.

PMID- 9234919
TI  - Metastatic breast carcinoma to the abdomen and pelvis.
AB  - OBJECTIVE: The role of surgical resection of metastatic breast cancer to the
      abdomen and pelvis is controversial. The objective of this study is to describe
      the characteristics, surgical management, and outcome of women with a history of
      breast adenocarcinoma who developed abdominal or pelvic metastases during follow
      up. METHODS: We retrospectively reviewed the medical records of 40 female
      patients with documented invasive breast cancer who were referred to the
      Gynecology Service between 1986 and 1995 and were found to have metachronous
      abdominal and/or pelvic metastases. RESULTS: The median patient age at
      exploration by the Gynecology Service was 53.5 years (range 27-79 years), and the
      median interval from breast cancer diagnosis to exploration was 80 months (range
      9-264 months). The majority of patients, 32 (80%), had a preoperative diagnosis
      of a new pelvic mass or suspected abdominal carcinomatosis. With a median follow
      up of 14.2 months following the diagnosis of abdominal or pelvic metastasis, the
      median survival for all patients was 24.1 months. Patients who had no gross
      residual disease in the abdomen or pelvis after surgery had a median survival of
      41.6 months, which did not significantly differ from those with gross residual <
      or =2 cm (16.1 months) or >2 cm (18.4 months) (P = 0.624). CONCLUSION:
      Metachronous abdominal and pelvic metastases from breast cancer may appear many
      years following initial diagnosis and are often operated on by gynecologists
      because of their clinical presentation. Surgical resection may be indicated in
      some symptomatic patients; however, the survival advantage of surgical
      cytoreduction remains to be determined.

PMID- 9234920
TI  - Hepatic resection for metastatic gynecologic carcinomas.
AB  - OBJECTIVE: To report a series of cases of hepatic resection for metastatic
      gynecologic carcinomas. METHODS: We reviewed the records of all patients who
      underwent hepatic resection for metachronous liver metastases from gynecologic
      carcinomas at our institution from 1986 to 1996. RESULTS: Twelve patients were
      identified with a median age of 60 years (range 30-73 years). The primary sites
      of carcinoma were as follows: ovary, 7 (58%); cervix, 2 (17%); endometrium, 2
      (17%); and fallopian tube, 1 (8%). The median disease-free interval before the
      diagnosis of liver metastasis was 32 months (range 1-243 months). The types of
      liver resections were as follows: trisegmentectomy, 4 (33%); lobectomy, 4 (33%);
      segmentectomy, 3 (25%); and wedge resection, 1 (8%). To remove all visible tumor
      with adequate margins, additional surgery included the following: resection of a
      portion of the diaphragm, 5 (42%); wedge resection of the right lung, 3 (25%);
      resection of a portion of the pericardium, 2 (17%); and adrenalectomy, 1 (8%).
      One patient (8%) had pulmonary wedge resections of bilateral pulmonary
      metastases. There was no perioperative mortality. Ten patients (83%) received
      additional chemotherapy. With a median follow-up of 25 months (range 8-94
      months), the median survival time is 27 months. Three patients (25%) have no
      evidence of tumor recurrence at 8, 17, and 38 months of follow-up. Nine patients
      (75%) have had tumor recurrence at a median of 12 months from the time of
      surgery. CONCLUSIONS: Hepatic resection of metachronous metastases from
      gynecologic carcinomas can be performed safely and may help prolong survival in
      carefully selected patients.

PMID- 9234922
TI  - Infrared spectroscopy of normal and abnormal cervical smears: evaluation by
      principal component analysis.
AB  - Fourier-transform infrared (FT-IR) spectra of malignant and dysplastic cervical
      scrapings were abnormal, as first described in our study of a limited number of
      samples, where the spectra were evaluated by visual inspection and peak intensity
      ratios. We have expanded our study to evaluate more cervical conditions, and to
      analyze the spectra by a chemometric approach (principal component analysis
      [PCA]). Cervical samples from 436 females were evaluated by FT-IR and
      Papanicolaou testing; 40/436 spectra were nonanalyzable. The remaining were as
      follows: normal, 174; malignant, 19; dysplasia, 8; atypia, 113; atrophy, 19;
      inflammatory, 47; bloody smear, 12; hypocellular, 4. PCA analysis followed by
      chi2 test revealed that statistically significant frequencies of being predicted
      malignant by FT-IR were associated with samples diagnosed as malignant (P <
      0.0001), and also those diagnosed as "atrophy" (P < 0.001), "atypical with bloody
      smear" (P < 0.05), "atypical with atrophic pattern" (P < 0.05), and "dysplasia"
      (P < 0.05). Based on these findings, for the diagnosis of cervical cancer by FT
      IR, as defined here, the sensitivity is 79%, the specificity is 77%, the positive
      predictive value is 15%, and the negative predictive value is 98.6%. Our findings
      (a) demonstrate the application of a chemometric approach to the study of
      cervical FT-IR spectra; (b) assess its potential diagnostic role; (c) suggest
      that atrophic and neoplastic samples share structural features; and (d) suggest
      that blood may interfere with such spectroscopic evaluation. These findings
      warrant further evaluation of FT- IR spectroscopy in cervical and other
      malignancies.

PMID- 9234921
TI  - A randomized trial of concurrent chemoradiotherapy versus radiotherapy in
      advanced carcinoma of the uterine cervix.
AB  - The purpose of our study was to determine whether the chemoradiation is better
      than radiotherapy alone with respect to survival and treatment toxicity in
      patients with advanced carcinoma of the cervix. From October 1990 to April 1995,
      a total of 122 patients with advanced cervical carcinoma were included in this
      study and randomly assigned to either radiotherapy or concurrent chemotherapy and
      radiotherapy. The patients in the concurrent group received cisplatin,
      vincristine, and bleomycin every 3 weeks for a total of four courses, in
      combination with radiotherapy concurrently. Sixty patients were randomized to the
      concurrent chemoradiotherapy, and 62 were randomized to the radiotherapy alone. A
      tumor response was observed in 88.3% of the patients in concurrent group and in
      74.2% of the patients in radiotherapy group (P = 0.04). After a median follow-up
      of 46.8 months, the overall disease-free survival and actuarial survival rate at
      3 years were 51.7 and 61.7% in the concurrent group, and 53.2 and 64.5% in the
      radiotherapy group, respectively. Treatment-related toxicity appears to be higher
      with the combination of radiotherapy and chemotherapy compared with radiotherapy
      alone (36.7% versus 17.7%, P = 0.02). However, analysis by Kaplan-Meier method
      showed that the actuarial survival was not statistically different between the
      chemoradiotherapy and radiotherapy groups (mean survival time: 38.1 months versus
      41.5 months, P = 0.27). In conclusion, this study showed that concurrent
      multiagent chemoradiotherapy did not prove to be a superior definitive therapy
      over radiotherapy alone for patients with advanced cervical carcinoma.

PMID- 9234923
TI  - Phase II trial of high-dose cisplatin plus ifosfamide as first-line followed by
      carboplatin as second-line treatment in epithelial ovarian carcinoma.
AB  - BACKGROUND: In a previous study of combined platinum and ifosfamide we found a
      pathologic complete response rate of 42%. The present study was to test whether
      the high response rate could be reproduced or even improved by combining high
      dose cis-platinum and increased dose of ifosfamide. METHODS: Forty-two previously
      untreated ovarian cancer patients were included in the study. Cisplatin 50 mg/m2
      and ifosfamide 2000 mg/m2 together with mesna 1200 mg/m2 were given daily, Day 1
      3 every 4 weeks for six cycles, followed by second-look laparotomy. In the event
      of residual disease carboplatin was given every 4 weeks for a further six cycles.
      RESULTS: The pathologic complete response rate was 20% (8 of 41). Five of 26
      patients achieved a further response on carboplatin. Hematologic and
      nonhematologic toxicity caused dose reduction in more than 90 and 50% of the
      patients, respectively. CONCLUSION: The results of this high-dose regimen equals
      those obtained with conventional, far less toxic, regimens. Only patients with
      potentially platinum-sensitive tumors achieved further response when crossed over
      to the analogue, which may indicate that prolonged treatment is better than
      increased dose. A randomized trial is still needed to assess the importance of
      dose intensity in ovarian cancer.

PMID- 9234924
TI  - Ovarian vein vs peripheral blood CA125 serum levels: a comparative study.
AB  - OBJECTIVE: Direct sampling from the ovarian vessels may be considered as a
      supplementary method of ovarian cancer diagnosis providing further clinical
      information for the staging and localization of ovarian carcinoma. This present
      multi-institutional study evaluates and compares the clinical values of CA125
      serum levels sampled directly from the right and left ovarian veins to the
      peripheral blood supply in an effort to correlate CA125 values to tumor volume
      and location. METHODS: Serum samples from 43 patients with primary ovarian
      carcinoma were evaluated for the presence of CA125. All patients underwent
      surgery for the primary tumor, and stage was defined according to the
      classification of the International Federation of Gynecology and Obstetrics. The
      measurement of CA125 was accomplished by radioimmunoassay. RESULTS: Twenty of 20
      patients with serous papillary adenocarcinoma, 8/12 patients with tumors of low
      malignant potential, 6/6 patients with endometrioid carcinoma, 2/4 patients with
      clear cell adenocarcinoma, and 1/1 patients with mucinous adenocarcinoma had
      elevated (>35 U/mL) peripheral CA125 levels. Peripheral blood CA125 values had
      Spearman correlation coefficients of 0.96 and 0.95 with left and right ovarian
      vein CA125 values, respectively. Similarly, left and right ovarian vein CA125
      values had a correlation coefficient of 0.98. CA125 values were moderately
      correlated with tumor volume in this sample. Spearman correlation coefficients
      between left ovarian vein CA125 values and left and right tumor volume were 0.51
      and 0.43, respectively. Spearman correlation coefficients between right ovarian
      vein CA125 levels and left and right tumor volume were 0.41 and 0.46,
      respectively. Those between peripheral CA125 values and left and right tumor
      volume were 0.56 and 0.36, respectively. Median CA125 values for stage I diseases
      were elevated (53.25, 101.5, and 74.50 for left, right, and peripheral,
      respectively). DISCUSSION: Direct sampling from the ovarian veins compared to
      that from the peripheral veins did not appear to offer additional information
      regarding ovarian tumor volume and location.

PMID- 9234925
TI  - Randomized study comparing carboplatin/cyclophosphamide and
      cisplatin/cyclophosphamide as first-line treatment in patients with stage III/IV
      epithelial ovarian cancer and small volume disease. German Ovarian Cancer Study
      Group (GOCA).
AB  - Several randomized studies in patients with advanced ovarian cancer have dealt
      with the comparison of cisplatin and carboplatin when given as either a single
      drug or in combination. The German Ovarian Cancer Study Group (GOCA) performed a
      prospective randomized trial in a subgroup of patients specified by a successful
      cytoreductive operation before the start of chemotherapy. From February 1987 to
      May 1990, 173 previously untreated patients with stage III and IV disease and
      limited tumor bulk of <2 cm postoperatively received either cyclophosphamide 600
      mg/m2 plus carboplatin 350 mg/m2 or cyclophosphamide 1000 mg/m2 plus cisplatin 80
      mg/m2. The drugs had to be administered on Day 1 every 28 days for six subsequent
      courses. RESULTS: In 158 assessable patients no significant differences in
      pathologically confirmed CR rates (pCR: 14% vs 16%), median time to progression
      (PFI: 19 months vs 26 months), and overall survival (OS: 35 months vs 37 months)
      were observed. Refusal of therapy due to toxicity was more frequent in the
      cisplatin arm, whereas patients with progressive disease predominated in the
      carboplatin arm. Nonhematologic adverse effects were more likely to occur with
      cisplatin whereas carboplatin patients experienced more myelosuppression. As
      prognostic factors associated with an increased risk of progressive disease and
      shorter overall survival time, stage of disease and amount of residual tumor
      after first surgery were determined. CONCLUSIONS: Carboplatin proved to be
      effective in patients with optimally debulked ovarian cancer. However, neither
      regimen used in this trial is sufficiently active to prevent tumor progression in
      the majority of patients.

PMID- 9234926
TI  - Preoperative D-dimer plasma assay is not a predictor of clinical outcome for
      patients with advanced ovarian cancer.
AB  - D-dimer (DD) plasma levels are significantly higher in patients with ovarian
      cancer than in those with benign ovarian masses. The aim of this paper is to
      assess whether preoperative DD plasma assay has a prognostic relevance for 35
      patients with advanced ovarian cancer receiving platinum-based chemotherapy.
      Preoperative DD levels ranged from 162 to 3720 ng/ml. The 25, 50, and 75%
      quartiles of DD levels were 1600, 1894, and 2069 ng/ml, respectively.
      Preoperative DD levels correlated neither with the common clinicopathological
      prognostic variables nor with the disease status at the end of first-line
      chemotherapy. Survival was related to residual disease after initial surgery (>
      or =2 cm vs <2 cm, P = 0.003), but not to preoperative DD levels. In conclusion,
      the present data seem to show that preoperative DD plasma assay is not a
      predictor of clinical outcome for patients with advanced ovarian cancer.

PMID- 9234927
TI  - Accuracy of three-dimensional ultrasonography in volume estimation of cervical
      carcinoma.
AB  - OBJECTIVE: To evaluate the accuracy of a three-dimensional (3D) ultrasound system
      in volume estimation of cervical carcinoma. STUDY DESIGN: Transvaginal 3D and two
      dimensional (2D) scans on cervical carcinoma volumes were performed 1 day before
      surgery. The volume of cervical carcinoma measured from each surgical specimen
      was compared with the corresponding volume of the cervical tumor measured by a 3D
      ultrasound and with the conventional 2D ultrasound volume measurement calculated
      using the formula pi/6 x(R1 x R2 x R3), where R1, R2, and R3 were the maximal
      transverse, anteroposterior, and longitudinal length of tumor, respectively.
      Limits of agreement and 95% confidence intervals were calculated and systemic
      bias between the methods was analyzed. The Klotz test was also used to assess the
      statistical significance of the degree of dispersion. RESULTS: A total of 61
      cases, 55 with exophytic tumors and 6 with endocervical tumors, were examined in
      this study. The limits of agreement between the volume measured from specimen and
      tumor volume determined by ultrasound were +6.68 to -6.10 mL for 3D measurements
      and +12.46 to -10.98 mL for 2D measurements. The Klotz test showed the
      discrepancy in the degree of dispersion between 3D and 2D ultrasound measurements
      was statistically significant (P = 0.01). CONCLUSION: The true volume of cervical
      carcinoma is measured more accurately by a 3D ultrasound system than 2D
      ultrasound.

PMID- 9234928
TI  - p53 interference and growth inhibition in p53-mutant and overexpressing
      endometrial cancer cell lines.
AB  - BACKGROUND: The presence of p53 mutations and associated mutant p53
      overexpression has been demonstrated in many cancer systems. Whether the
      overexpression of mutant p53 represents cause or effect, and whether p53 mutation
      contributes actively to the malignant phenotype is a matter of controversy. We
      examined the growth effects of oligonucleotides designed to interfere with p53
      expression and/or activity in p53-mutant/overexpressing endometrial cancer cell
      lines. METHODS: Phosphorothioate oligonucleotides were used to target p53-related
      sequences in two p53-mutant/overexpressing endometrial cancer cell lines (KLE and
      RL95-2) and a normal fibroblast control. The ATP cell viability assay was used to
      measure growth effects after 6-day treatments with 27-mer and 14-mer sense (S) or
      antisense (AS) phosphorothioate oligodeoxyribonucleotides (oligos) targeting the
      promoter/ATG region of p53 and/or the p53 consensus (CON) DNA binding sequence.
      These sequences were designed to interfere with p53 expression and activity,
      respectively. Random sequences of the p53 27- and 14-mer were used as controls
      for nonspecific oligo effects, and a normal fibroblast cell line was used to
      compare oligo effects and serve as a negative p53 immunostaining control.
      RESULTS: Mean +/- SE IC50 (50% growth inhibition) of the S, AS p53, and p53 CON
      oligos were 4.2 +/- 1.3, 4.7 +/- 0.9, and 7.6 +/- 1.4 microM, respectively, for
      the two endometrial cell lines combined. The AS and S p53 oligos demonstrated
      dose-dependent inhibitory effects in both cell lines, while p53 CON produced
      variable effects alone and in combination with p53 AS. In KLE, a uniform
      inhibitory dose response was seen with p53 CON oligos. In RL95-2, the approximate
      IC50 for p53 CON was 0.5-1.0 microM, but at increasing doses above this, an
      inverse dose response was consistently observed. Combinations of p53 AS and p53
      CON oligos produced predominantly synergistic growth inhibition. Although
      combinations of p53 AS and p53 CON in KLE were synergistic at low doses,
      antagonistic effects occurred at higher concentrations. Oligos had little effect
      on normal fibroblast growth, with calculated IC50 > 16 microM. Equimolar
      combinations of p53 S and AS were antagonistic, indicating that antiproliferative
      effects were sequence-specific. Random oligos demonstrated some nonspecific
      inhibitory effects, with >25% growth inhibition at 16 microM and beyond.
      Immunoperoxidase staining for mutant p53 after exposure to 16 microM
      concentrations of p53 AS oligos demonstrated reductions in p53 staining but
      persistent overexpression relative to wild-type (fibroblast) cells. CONCLUSION:
      Phosphorothioate oligos directed against p53 sequences in two p53-mutant
      endometrial cancer cell lines demonstrated antiproliferative effects. Combined
      anti-p53 and anti-p53 binding site oligos resulted in predominantly synergistic
      antiproliferative effects. The activity of sense oligos, the variable responses
      to p53 CON, and the persistent overexpression of mutant p53 at high
      concentrations of growth-inhibiting anti-p53 oligos suggest that, while
      promising, the antineoplastic effects of these oligos occur through complex and
      incompletely understood mechanisms.

PMID- 9234929
TI  - Estrogen replacement therapy following oophorectomy in women with a family
      history of ovarian cancer.
AB  - Compliance with estrogen replacement therapy (ERT) following surgical menopause
      is poor. In women who have a family history of ovarian cancer, fear of the
      oncogenic potential of estrogen might affect compliance with ERT following
      oophorectomy. Compliance with ERT in such a select group of women has not been
      previously reported. The aim of the present study was to report on compliance
      with and side effects of ERT in women with a family history of ovarian cancer who
      underwent oophorectomy either prophylactically or for benign disease. Eighty
      women with a family history of ovarian cancer who underwent oophorectomy at
      Roswell Park Cancer Institute were followed for a median duration of 4.2 years
      (range, 5 months to 14 years). Of the 76 women who were given prescriptions for
      ERT, the rates of commencement and maintenance of ERT at 1, 2, and 5 years were
      calculated. Side effects related to the different modalities of ERT were
      recorded. Seventy-one of 76 women (93.4%) who were given prescriptions for ERT
      initiated treatment. The rate of commencement of ERT was higher in premenopausal
      than in postmenopausal women (98.3% versus 75%, respectively, P = 0.003). Except
      for one patient who developed breast cancer after the oophorectomy and was
      advised to stop estrogen, all patients said they continued to use ERT. The
      maintenance rates at 1, 2, and 5 years were 100% as per patients' history. The
      pharmacy records for ERT prescription refills were reviewed for 52 patients who
      were on ERT for more than 1 year. ERT compliance was confirmed in 42 patients
      (80.7%). Seven of 30 patients (23.3%) who retained their uterus developed
      irregular uterine bleeding and 4 underwent endometrial biopsies. The incidence of
      irregular uterine bleeding was significantly higher after continuous compared to
      cyclic estrogen and progestogen (37.6 and 7% respectively, P = 0.049). Four
      patients (5.6%) complained of hot flashes and were managed by changing the dose
      or formula of estrogen. Compliance with ERT among patients with a family history
      of ovarian cancer who underwent oophorectomy either prophylactically or for
      benign disease was excellent. The presence of the uterus and the incidence of
      irregular uterine bleeding did not affect patients' compliance with ERT.

PMID- 9234930
TI  - Human papillomavirus analysis as a prognostic marker following conization of the
      cervix uteri.
AB  - Cervical intraepithelial neoplasia grade 3 (CIN 3) is treated surgically. Follow
      up of these patients is important to ensure successful treatment. The present
      study was undertaken to determine whether human papillomavirus (HPV) testing can
      be used to discriminate patients who will have recurrences from those who will
      not. It is composed of 26 patients who presented with recurrences of CIN and 22
      patients who remained disease-free after treatment. DNA was extracted from
      paraffin-embedded cone biopsies of incident CIN 3, their corresponding follow-up
      Pap smears taken 3 months postoperatively, and their secondary cone biopsies of
      the recurrent lesions. The extracted DNA were then analyzed by PCR for the
      presence of HPV. The posttreatment cervical smears in the recurrent group had a
      (25/26) 96% HPV prevalence, while HPV DNA was not detectable in any of the 22
      patients in the control group. The HPV types in both the initial and recurrent
      lesions correlated very well. This suggest that most recurrences are likely to be
      due to persisting lesions or subclinical HPV infections that had not been
      completely removed. Cytology alone was not sufficiently sensitive to discriminate
      the patients at risk for recurrences. It appears that HPV testing can be useful
      to monitor the therapeutic result.

PMID- 9234931
TI  - Biological assay for activity and molecular mechanism of retinoids in cervical
      tumor cells.
AB  - The composition and response of the retinoid signaling pathway in a human cell
      line (CC-1), representative of a low grade cervical carcinoma, were evaluated.
      Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated
      expression of cytoplasmic retinol binding protein, CRBPI, cytoplasmic retinoic
      acid binding protein, CRABPII, and nuclear retinoic acid receptors, RAR alpha,
      RARgamma, RXR alpha, and RXRbeta, but not CRABPI or RARbeta. This pattern is
      similar to that of the ectocervix. Activation of endogenous nuclear receptors was
      evaluated in a reporter subline of CC-1, called CC-B, containing a reporter gene
      controlled by a retinoic acid responsive element (RARE) and thymidine kinase
      promoter. Retinoid treatment of CC-B resulted in dose-dependent increases in
      reporter gene expression. Retinoids inhibited growth at concentrations greater
      than 100 nM. 9-cis retinoic acid (1 nM) significantly stimulated growth.
      Immunohistochemical analysis of CC-B organotypic cultures demonstrated a high
      level of epidermal growth factor receptor (EGF-R) expression that was decreased
      by retinoids. The degree of RARE transactivation induced by retinoids
      significantly correlated with the degree of inhibition of growth (R = -0.96) and
      EGF-R expression (R = -0.92). The dose-dependent and retinoid-specific responses
      of CC-1 at the molecular and biological levels demonstrate the utility of this
      reporter cell line for evaluation of retinoid activities.

PMID- 9234933
TI  - The in vitro effect on T cell function of soluble IL-2Ralpha from advanced
      ovarian cancer ascites.
AB  - Activated T cells not only secrete interleukin-2 (IL-2) and express cell surface
      interleukin 2 receptor alpha (IL-2R alpha), but also shed IL-2R alpha. This
      soluble receptor is a truncated form of the membrane-bound p55 receptor with a
      similar binding affinity. It has been proposed that soluble IL-2R alpha (sIL-2R
      alpha) could negatively modulate local immune response. High levels of sIL-2R
      alpha have been found in the serum and ascites of ovarian cancer patients. The
      purpose of this investigation is to determine the amount of in vitro T cell
      inhibition seen in ovarian cancer ascites that is attributable to high levels of
      sIL-2R alpha. Purified sIL-2R alpha at levels up to 100,000 pg/ml was placed in
      lymphocyte proliferation assays. Soluble IL-2R alpha was removed from the ascites
      of three patients with advanced ovarian cancer. Lymphocyte proliferation assays
      utilizing phytohemaglutin (PHA) stimulation were carried out with this ascites.
      Untreated ascites from each patient served as control. Addition of purified sIL
      2R alpha to lymphocyte proliferation assays failed to demonstrate significant
      lymphocyte suppression. Addition of ascites to the lymphocyte assays resulted in
      up to an 80% decrease in lymphocyte proliferation. Neutralization of ascites sIL
      2R alpha as well as removal of sIL-2R alpha via a protein G column failed to
      reverse any of the observed lymphocyte suppression. We conclude that although
      sIL2R alpha is elevated in ascites of patients with ovarian cancer, it does not
      account for the profound ascites-induced T cell suppression observed in vitro.

PMID- 9234934
TI  - The feasibility of open laparoscopy in gynecologic-oncologic patients.
AB  - Gynecologic-oncologic patients are at increased risk for complications with
      closed laparoscopy. Open laparoscopy eliminates the steps of blind insufflation
      and trocar insertion. This study is the first large series of open laparoscopies
      to assess the feasibility and safety of the open laparoscopy technique in
      patients with gynecologic malignancies. We performed 90 open laparoscopies in 89
      oncologic patients with previous major surgery (65%) and/or radiotherapy (17%) or
      a large omental cake (18%). Complications due to the laparoscopic access
      technique occurred in one patient (1%) for whom a laparotomy was performed for a
      small bowel perforation. The incidence of complications of the open laparoscopy
      technique (1%) is favorable compared to the complication rate of closed
      laparoscopy in gynecologic-oncologic patients. It is concluded that open
      laparoscopy is a safe and feasible technique in gynecologic-oncologic patients.

PMID- 9234932
TI  - In vivo fluorescence detection of ovarian cancer in the NuTu-19 epithelial
      ovarian cancer animal model using 5-aminolevulinic acid (ALA).
AB  - The purpose of this study was to determine whether in vivo fluorescence detection
      of protoporphyrin IX (PpIX) could be used to identify intraperitoneal
      micrometastases of epithelial ovarian carcinoma after application of 5
      aminolevulinic acid (ALA). ALA was applied intraperitoneal at different
      concentrations (25, 50, and 100 mg/kg) and iv (100 mg/kg) to immunocompetent
      Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. At different
      time intervals after ALA administration (1.5, 3, and 6 hr) the peritoneal cavity
      was illuminated with ultraviolet (uv) light. In vivo fluorescence of PpIX
      initially was determined by direct visualization. Subsequently ex vivo
      measurements were made with a slow-scan, thermoelectrically cooled CCD camera.
      Red in vivo fluorescence was observed in ovarian micrometastases smaller than 0.5
      mm in 100% of the ALA-administered animals independent of time interval, drug
      concentration, or route of administration. The intensity of the fluorescence was
      concentration dependent as strong fluorescence was consistently found only above
      25 mg/kg ALA. Ex vivo tumor to peritoneum fluorescence yield peaked 3 hr after
      administration of a 100 mg/kg intraperitoneal dose. Direct visualization of in
      vivo fluorescence after ALA application may improve the detection of
      intraperitoneal ovarian cancer micrometastases.

PMID- 9234935
TI  - Squamous metaplasia of the endometrium associated with HPV 6 and 11.
AB  - Although uncommon in the endometrium, squamous metaplasia, dysplasia, and
      squamous carcinoma have been observed. Associated human papillomavirus (HPV)
      infection is also unusual, due at least in part to the fact that HPV requires
      specific characteristics of the target epithelium for infectivity. We report a
      case of extensive squamous metaplasia with focal low-grade squamous
      intraepithelial neoplasia of the endometrium coexistent with low-grade cervical
      intraepithelial neoplasia and an invasive squamous carcinoma of the vagina. In
      situ hybridization studies revealed HPV types 6 and 11 in both the cervical and
      endometrial lesions. This is the first report to date to demonstrate squamous
      epithelial metaplasia and dysplasia of the endometrium, associated with HPV DNA
      of viruses typically of low oncogenic potential.

PMID- 9234936
TI  - Extramammary Paget's disease of the vulva: metastases to the bone marrow in the
      absence of an underlying adenocarcinoma--case report and literature review.
AB  - A case of Paget's disease of the vulva is presented which, over a period of 6
      years, was characterized by local recurrences and metastases to the bone marrow.
      Detailed examination of multiple sections of the primary tumor and of the bone
      marrow biopsy specimen failed to demonstrate an underlying adenocarcinoma in any
      of the sites. The routine histologic staining and immunohistochemical staining
      demonstrated that the metastatic cells strongly correlated with cells from the
      vulvar lesion. Specifically, immunohistochemical staining of the specimens from
      the primary and metastatic sites was positive for the gross cystic disease fluid
      protein-15, which has been associated with extramammary Paget's disease
      uncomplicated by underlying malignancies. Finally, during several years of close
      follow-up, no other primary site of Paget's disease declared itself clinically or
      was found by radiographic studies or analysis of serum tumor markers.

PMID- 9234937
TI  - Port site metastasis after laparoscopic-assisted vaginal hysterectomy for
      endometrial cancer: possible mechanisms and prevention.
AB  - Only 19 cases of metastases at the cannula insertion site after laparoscopy for
      gynecological malignancy have been reported in the literature. One case has been
      diagnosed with cervical squamous cell carcinoma, whereas the others have been
      diagnosed with ovarian cancer and borderline ovarian tumor. We present a novel
      case of laparoscopy-site abdominal wall metastasis from endometrial cancer after
      laparoscopic-assisted vaginal hysterectomy (LAVH). The 56-year-old female patient
      exhibited metastases of an abdominal wall trocar site and a perineal site after
      undergoing LAVH and laparoscopic-assisted (LA) bilateral pelvic lymph node
      sampling as well as LA para-aortic lymph node sampling for treating endometrial
      carcinoma, surgical staging IIIC, G3. The interval between the surgical
      extirpation of endometrial carcinoma and diagnosis of the tumor recurrence was 6
      months, suggesting that overmanipulation of the diseased organ during
      laparoscopic surgery may have resulted in tumor spillage, intraperitoneal
      dissemination, and wound contamination. Although this procedure has been proven
      beneficial to patients with benign disease or early-stage gynecologic
      malignancies, laparoscopic-assisted vaginal hysterectomy may not be efficacious
      to eradicate advanced gynecological malignancy.

PMID- 9234938
TI  - Complete hydatidiform mole coexisting with a twin live fetus: clinical course.
AB  - A 33-year-old G4P0 white female presented for a pregnancy ultrasound at 9 weeks
      gestation and was found to have a complete hydatidiform mole coexisting with a
      live twin fetus (CHTF). The beta-hCG level was 600,000 mIU/ml and the chest X ray
      was negative. The pregnancy was uneventfully terminated by suction curettage and
      oral contraceptives were prescribed. The initial beta-hCG declined appropriately;
      however, it subsequently rose. The metastatic workup was negative and the patient
      was treated with weekly intramuscular methotrexate at 30 mg/m2. The hCG levels
      declined appropriately and then plateaued. Salvage chemotherapy with intravenous
      actinomycin D at 1.25 mg/m2 every 14 days was started. The hCG level normalized
      after 3 cycles and the patient was free of disease at 1 year follow-up.

PMID- 9234939
TI  - Primary peritoneal adenocarcinoma metastatic to the brain.
AB  - Primary peritoneal adenocarcinoma is a relatively newly identified disease entity
      whose clinical behavior is not fully recognized. We report a case of a patient
      with progressive primary peritoneal adenocarcinoma who developed brain metastases
      and died shortly afterward. The incidence of central nervous system metastases in
      72 patients with documented primary peritoneal adenocarcinoma was 1.4%. The risk
      factors, clinical behavior, and prognosis of patients with primary peritoneal
      adenocarcinoma metastatic to the central nervous system seem to be similar to
      those of patients with epithelial ovarian cancer metastatic to the central
      nervous system.

PMID- 9234940
TI  - Parity as an independent prognostic factor in malignant mixed mesodermal tumors
      of the endometrium.

PMID- 9234941
TI  - Intra-abdominal spread of malignant cells following hysteroscopy.

PMID- 9234942
TI  - Early detection of the lytic LMP-1 protein in EBV-infected B-cells suggests its
      presence in the virion.
AB  - The Epstein-Barr virus (EBV)-positive B958 cell line expresses two related
      membrane proteins encoded by BNLF-1 open reading frames. One protein (LMP-1) has
      been shown to be essential for the growth transforming properties of EBV. The
      second protein (the lytic LMP-1) is an amino-terminally truncated form of LMP-1
      whose expression is associated with induction of EBV's lytic cycle. We have
      investigated the expression of full-length and lytic forms of LMP-1 immediately
      after infection of the EBV-negative, B-lymphoma cell line BJAB. Only the lytic
      LMP-1 protein is present in BJAB cells early (within minutes following addition
      of virus) after infection with virus derived from either uninduced or
      tetradecanoyl phorbol acetate and sodium butyrate-induced B958 cells. Lytic LMP-1
      protein levels begin to decline by 48 hr after infection, whereas levels of full
      length LMP-1 increase between 24 and 48 hr after infection and then remain
      constant. The presence of the lytic LMP-1 protein in infected cells is
      independent of both protein synthesis and virus internalization. We also find the
      lytic LMP-1 protein in BJAB cells early after infection (within 3 hr of addition
      of virus) with the HH514 strain of EBV, and HH514 cells treated with
      tetradecanoyl phorbol acetate and sodium butyrate, express high levels of both
      the lytic LMP-1 and full-length LMP-1 proteins. The lytic LMP-1 protein is
      enriched in purified virion preparations, and immunoelectron microscopic analysis
      indicates that EBV virions can be specifically labeled with anti-LMP-1 antisera.
      Together, these results are consistent with a model in which the lytic LMP-1
      protein is present in the EBV virion and is carried into the B-cell upon
      infection and suggest a role for this protein in early infection events and/or in
      EBV's lytic cycle.

PMID- 9234943
TI  - Comparative analyses of LTRs of the ERV-H family of primate-specific retrovirus
      like elements isolated from marmoset, African green monkey, and man.
AB  - We have isolated 8 different long terminal repeat (LTR) sequences of the ERV-H
      family of endogenous retrovirus-like elements from human chromosome 18, 9 from
      African green monkey, and 28 from marmoset. Human ERV-H LTRs have been divided
      into three types designated Type I, Type Ia, and Type II. Comparative analyses of
      the 45 isolated LTRs and 60 human ERV-H LTRs enabled a further subdivision into
      13 subtypes. Type I elements were widely distributed in all three species. Their
      average evolutionary age (40 MYr), estimated by a consensus sequence approach,
      suggests that they first expanded in the genomes at the time New- and Old World
      monkeys diverged. The occurence of some very old Type I sequences indicate that
      ERV-H elements may have integrated even before prosimians and primates diverged.
      Type Ia and - II elements were found in both monkey species. Promoter active Type
      I and Type Ia LTRs were found while Type II LTRs were inactive. Promoter active
      Type I LTRs generally contained a functional GC/GT box immediately 3' to the TATA
      box, providing strong binding of Sp1 family proteins, while the highly promoter
      active Type Ia element H6 contained synergistically acting Sp1 binding sites
      located in the U3 enhancer region.

PMID- 9234944
TI  - Proteins C and NS4B of the flavivirus Kunjin translocate independently into the
      nucleus.
AB  - The subcellular locations in infected Vero cells of Kunjin (KUN) virus core
      protein C and NS4B were analyzed by immunofluorescence (IF) and by immunoelectron
      microscopy using monospecific antibodies. Selection of appropriate fixation
      methods for IF showed that both proteins were associated at all times with
      perinuclear membranes spreading outward in a reticular pattern and they entered
      the nucleus late during the latent period. Subsequently NS4B was also dispersed
      through the nucleoplasm, while C appeared in the nucleolus and the nucleoplasm.
      These nuclear locations were confirmed by immunogold labeling of cryosections of
      infected cells at 24 hr postinfection. Labeling of NS4B in cryosections was
      especially enriched in the perinuclear membranes of the endoplasmic reticulum.
      When C and NS4B were each expressed separately in stably transformed cell lines,
      both cytoplasmic and nuclear localization was observed by IF and confirmed by
      immunoelectron microscopy. Thus the two proteins translocated to the nucleus
      independently of each other and of other viral proteins. Dual IF with antibodies
      to double-stranded RNA showed that cytoplasmic locations of C and NS4B were
      apparently associated in part with the sites of viral RNA synthesis which were
      resistant to solubilization by Triton X-100.

PMID- 9234945
TI  - Transduction of the human immunodeficiency virus type 1 promoter into human
      chromosomal DNA by adeno-associated virus: effects on promoter activity.
AB  - Transcription of the human immunodeficiency virus type 1 (HIV-1) genome takes
      place after integration of the provirus into human chromosomal DNA. HIV
      transcription is known to be modulated by viral and cellular factors but the
      influence of flanking chromosomal sequences on proviral gene expression has not
      been well defined. To investigate the activity of the integrated HIV promoter, we
      exploited the ability of recombinant adeno-associated virus (AAV-2) to transfer
      and stably integrate genes into the human genome at random or site-specifically.
      Chimeric AAV vectors were constructed containing an HIV-CAT reporter cassette;
      some vectors also contained the neomycin resistance gene to facilitate the
      isolation of positive clones. HeLa cells were infected with recombinant AAV, in
      some instances together with wild-type virus as a source of AAV rep function. We
      isolated 25 clones of G418-resistant cells which carried the integrated HIV-CAT
      cassette, generally occupying unique sites that did not correspond to the AAV
      specific region of chromosome 19. The HIV promoter was transcriptionally active
      in most of the clones. Basal promoter activity varied substantially among the
      clones, and its responsivity to the HIV transactivator Tat was also variable. The
      integrated HIV promoter was transactivated to comparable degrees by the one-exon
      form and two-exon form of Tat. These findings provide evidence that the
      transcriptional activity of the HIV promoter can be greatly influenced by the
      site of proviral insertion.

PMID- 9234946
TI  - Masking of retroviral envelope functions by oligomerizing polypeptide adaptors.
AB  - We have constructed chimeric retroviral envelopes displaying N-terminal
      polypeptides that are known to form homotrimeric associations. The amphotropic
      receptor (RAM-1) binding domain from the trimeric surface (SU) glycoprotein of
      4070A murine leukemia virus (MLV)-inhibited ecotropic receptor (Rec-1) mediated
      infection by the SU glycoprotein of Moloney MLV when grafted to its N-terminus.
      The block to Rec-1-mediated infection was reversed when the RAM-1 binding domain
      was cleaved from the vector particles using an engineered factor Xa protease
      sensitive cleavage signal between the envelope glycoprotein and its N-terminal
      extension. Trimeric leucine zipper peptides and the trimeric C-terminal domain of
      CD40 ligand were shown to inhibit RAM-1-mediated infection of NIH3T3 cells by the
      4070A envelope when fused to its N-terminus, whereas monomeric helical peptides
      and the monomeric epidermal growth factor domain did not. The block to RAM-1
      mediated infection was reversed when the trimeric polypeptides were cleaved from
      the vector particles by addition of factor Xa protease. Envelope binding assays
      using cleaved and uncleaved chimeric 4070A envelopes revealed that binding to RAM
      1 receptors on mammalian cells was hindered by trimeric, but not by monomeric, N
      terminal polypeptides. These results have important implications for the design
      of protease-activatable vectors for targeted gene delivery.

PMID- 9234947
TI  - The signal sequence of lymphocytic choriomeningitis virus contains an
      immunodominant cytotoxic T cell epitope that is restricted by both H-2D(b) and H
      2K(b) molecules.
AB  - Infection of H-2b mice with lymphocytic choriomeningitis virus (LCMV) generates
      three well-characterized H-2D(b)-restricted immunodominant epitopes delineated in
      the NP, GP1, and GP2 proteins. Here we report that the H-2D(b)-restricted GP1
      epitope GP33-41/43 (KAVYNFATC/GI) located in the signal sequence of LCMV is also
      the immunodominant epitope recognized by CTL at the surface of the same infected
      cells in the context of H-2K(b) restriction. The GP1 epitope bound to H-2D(b) and
      H-2K(b) molecules with comparable affinities. The respective binding processes
      involved different sets of peptide anchoring residues and required dramatically
      different conformations of the peptide backbone as well as rearrangement of
      residue side chains. The 10-mer peptide GP34-43 (AVYNFATCGI) was the optimal H
      2K(b)-binding sequence and the 8-mer peptide GP34-41 (AVYNFATC) the minimal
      sequence for optimal H-2K(b)-restricted CTL recognition. Comparison of lytic
      activities of primary splenic anti-LCMV CTL from C57BL/6 (D(b+)/K(b+)), B10A.[5R]
      (D(b-)/K(b+)), and B10A.[2R] (D(b+)/K(b-)) mice against LCMV-infected or peptide
      coated target cells expressing either one or the two MHC alleles revealed that
      the H-2K(b)-restricted component of the anti-GP1 CTL response was mounted
      independently of but as efficiently as its H-2D(b) counterpart. Analysis of the
      immune response against a GP1 variant that escapes CTL recognition showed that
      the GP1 epitope: (i) was likely the only immunodominant LCMV epitope in the
      context of H-2K(b), and (ii) could efficiently evade H-2D(b) and H-2K(b)
      restricted CTL mediated lysis.

PMID- 9234948
TI  - Minimum protein requirements for transcription and RNA replication of a
      minigenome of human parainfluenza virus type 3 and evaluation of the rule of six.
AB  - A reconstituted transcription and RNA replication system for human parainfluenza
      virus type 3 (HPIV3) was developed using components expressed intracellularly
      from transfected plasmids driven by T7 RNA polymerase supplied by a vaccinia
      virus recombinant. The system is based on a negative-sense analog of HPIV3
      genomic RNA in which the viral genes were deleted and replaced with that encoding
      bacterial chloramphenicol acetyl transferase (CAT). The N, P, and L proteins
      expressed from cotransfected plasmids were necessary and sufficient to direct
      efficient transcription and RNA replication. Transcription yielded subgenomic
      polyadenylated mRNA, which was isolated by oligo(dT) chromatography. RNA
      replication yielded a mini-antigenome and progeny minigenome, which were shown to
      be encapsidated based on resistance to digestion with micrococcal nuclease. A
      panel of cDNAs was constructed to encode minigenomes which differed in length by
      single-nucleotide increments. Transcription and RNA replication in the
      reconstituted system were most efficient for the minigenome whose length was an
      even multiple of six. Both RNA replication and transcription appeared to be
      governed by the rule. However, minigenomes whose lengths were one nucleotide
      greater than or less than an even multiple of six also were very active,
      especially in RNA replication, indicating that the rule was not absolute.

PMID- 9234949
TI  - Interaction of the viral protein genome linked of turnip mosaic potyvirus with
      the translational eukaryotic initiation factor (iso) 4E of Arabidopsis thaliana
      using the yeast two-hybrid system.
AB  - The yeast LexA interaction trap was used to screen a cDNA library from
      Arabidopsis thaliana in order to identify proteins that interact with the viral
      protein genome linked (VPg)-proteinase of turnip mosaic potyvirus. The screen
      allowed the isolation of four candidate cDNA clones. Clones pHC4, pHC21, and
      pHC40 were partially sequenced but no homologies to known proteins were found.
      However, the amino acid sequence deduced from the complete nucleotide sequence of
      pSW56 revealed that it was the eukaryotic initiation factor (iso) 4E
      [eIF(iso)4E]. Deletion analysis indicated that the VPg domain was involved in the
      interaction with the plant protein. Interaction between the viral protein and the
      cellular protein was confirmed by ELISA-based binding experiments. eIF(iso)4E
      plays an essential role in the initiation of the translation of capped mRNAs and
      its association with VPg would point to a role of the viral protein in the
      translation of the virus.

PMID- 9234950
TI  - Chimeric papillomavirus-like particles.
AB  - We have constructed chimeric papillomavirus-like particles (CVLPs) by replacing
      the 34-carboxy-terminal amino acids of the HPV 16 L1 protein with various parts
      of the HPV 16 E7 protein. Chimeric proteins were expressed by recombinant
      baculoviruses and analyzed by electron microscopy for their ability to assemble
      into virus capsids. We were able to produce CVLPs in high efficiencies with
      inserts of up to 60 amino acids. CVLPs are able to induce a neutralizing antibody
      response, assayed by inhibition of hemagglutination of mouse erythrocytes. CVLPs
      are interacting with the putative receptor for papillomaviruses as they were
      shown to hemagglutinate mouse red blood cells and bind to and penetrate cells in
      vitro. As CVLPs follow a similar intracellular pathway as observed earlier for
      BPV VLPs, we speculate that CVLPs can be used to deliver peptides into mammalian
      cells in vitro and in vivo, possibly reaching the pathway for MHC class I
      presentation.

PMID- 9234951
TI  - Viral determinants of pea early browning virus seed transmission in pea.
AB  - Pea early browning virus (PEBV) is a member of the genus, Tobravirus. It is
      transmitted by soil-inhabiting trichodorid nematodes and through seeds from
      diseased plants. By introducing mutations into the PEBV genome, we have studied
      the viral determinants of seed transmission in pea. Neither deleting a portion of
      the genome containing the three nonstructural genes in RNA2 nor the interuption
      of any of the three genes individually prevented PEBV seed transmission. However,
      a comparison of two PEBV isolates indicated a minor role for RNA2 or its
      products. In contrast, the removal of the coding sequence of the 12K gene in RNA1
      almost completely abolished viral seed transmission. The virus lacking the 12K
      gene caused more severe symptoms on leaves and pods, and accumulated to a higher
      level than the wild-type virus in both types of tissues. However, the 12K
      deletion mutant accumulated poorly in anthers and carpels, and could not be
      detected in pollen grains and ovules. These results suggest that the 12K gene is
      involved in the infection of the gametic cells and hence the seed transmission of
      PEBV in pea.

PMID- 9234952
TI  - Protective immune responses induced by the immunization of mice with a
      recombinant bacteriophage displaying an epitope of the human respiratory
      syncytial virus.
AB  - We investigated whether a recombinant bacteriophage displaying a disease-specific
      protective epitope could be experimentally used as a vaccine to confer protection
      of immunized animals against infection. We genetically engineered a recombinant
      phage, fd, displaying at its surface a chimeric pIII coat protein fused to the
      previously identified protective epitope 173-187 from the glycoprotein G of the
      human respiratory syncytial virus (RSV). A selected recombinant fd phage elicited
      a strong immune response in mice, inducing a high level of circulating RSV
      specific antibodies. Mice immunized with the recombinant phage acquired a
      complete resistance to RSV infection as evidenced by the lack of detectable virus
      particles in their lungs following intranasal challenge with live RSV. In
      contrast, a high level of virus particles was found in the lungs of either
      animals immunized with the wild-type fd phage or nonimmunized mice. To our
      knowledge, this is the first study to report the ability of a phage presenting an
      immunogenic peptide to prevent infection of immunized animals by a pathogen. This
      finding should facilitate the identification of pathogen-specific protective
      epitopes selected from random phage peptide libraries, as it is simpler and less
      expensive than the conventional method of synthesis and coupling of phage
      specific peptide ligand sequences for immunization.

PMID- 9234953
TI  - Signaling via the CD2 receptor enhances HTLV-1 replication in T lymphocytes.
AB  - Human T lymphotropic virus type 1 (HTLV-1) is considered the etiologic agent of
      adult T cell leukemia/lymphoma and several chronic progressive immune-mediated
      diseases. Approximately 1-4% of infected individuals develop disease, generally
      decades following infection. Increased proviral transcription, mediated by the
      viral 40-kDa trans-activating protein, Tax, has been implicated in the
      pathogenesis of HTLV-1-associated diseases. Since the HTLV-1 promoter contains
      sequences responsive to cyclic AMP and protein kinase C, we hypothesized that
      lymphocyte activation signals initiated through the TCR/CD3 complex or CD2
      receptor promote viral replication in HTLV-1-infected lymphocytes. We demonstrate
      that mAbs directed against the CD2, but not the CD3 receptor increase viral p24
      capsid protein 1.5- to 5.7-fold in CD2/CD3+ HTLV-1-infected cell culture
      supernatants. Northern blot analysis demonstrated a 2.5- to 4-fold increase in
      all species of viral mRNA following CD2 cross-linking of OSP2/4 cells, an
      immortalized HTLV-1 cell line. Consistent with transcriptional regulation,
      reporter gene activity increased approximately 11-fold in CD2-stimulated Jurkat T
      cells cotransfected with a Tax-expressing plasmid and a CAT reporter gene
      construct under control of the HTLV-1 promoter. These data suggest a possible
      physiologic mechanism, whereby CD2-mediated cell adhesion and lymphocyte
      activation may promote viral transcription in infected lymphocytes.

PMID- 9234954
TI  - Expression, assembly, and proteolytic processing of Helminthosporium victoriae
      190S totivirus capsid protein in insect cells.
AB  - The dsRNA genome (5.2 kbp) of Helminthosporium victoriae 190S totivirus (Hv190SV)
      consists of two large overlapping open reading frames (ORFs). The 5' proximal ORF
      codes for the capsid protein (CP) and the 3' ORF codes for an RNA-dependent RNA
      polymerase. Although the capsid of Hv190SV is encoded by a single gene, it is
      composed of two major closely related polypeptides, either p88 and p83 or p88 and
      p78. Whereas p88 and p83 are phosphoproteins, p78 is nonphosphorylated.
      Expression of the CP ORF in insect cells generated both p78 and p88 which
      assembled into virus-like particles. The finding that p78, p83, and p88 share a
      common N-terminal amino acid sequence is consistent with the determination that N
      terminal, but not C-terminal, CP deletions were incompetent for assembly.
      Evidence was obtained that p78 is derived from p88 via proteolytic cleavage at
      the C-terminus. Proteolytic processing may play a regulatory role in the virus
      life cycle since it leads to dephosphorylation of CP and a subsequent decrease in
      virion transcriptional activity.

PMID- 9234955
TI  - A cucumber necrosis virus variant deficient in fungal transmissibility contains
      an altered coat protein shell domain.
AB  - Little is currently known regarding the specific interactions that govern
      transmission of plant viruses by their vectors. A cucumber necrosis virus (CNV)
      variant (LL5) deficient in fungal transmissibility has been isolated from
      mechanically passaged CNV and characterized. Although LL5 accumulates to wild
      type (WT) levels, is capable of rapid systemic infection, and produces stable,
      highly infectious particles, it is only inefficiently transmitted by Olpidium
      bornovanus zoospores. The LL5 coat protein (CP) gene was amplified by RT-PCR and
      cloned in place of the WT CNV CP gene in an infectious CNV cDNA clone. Particles
      derived from this construct also failed to be efficiently transmitted. The LL5 CP
      gene was sequenced and found to contain two amino acid substitutions relative to
      WT CNV CP. One substitution (Phe to Cys) occurred in the arm region and another
      (Glu to Lys) in the shell domain. These amino acid changes were separately
      introduced into the WT CNV genome through in vitro mutagenesis and it was found
      that the Glu to Lys change in the LL5 CP shell domain is largely responsible for
      the loss of transmissibility. In vitro binding assays were developed to determine
      if the defect in transmissibility was due to a defect in binding zoospores. LL5
      particles were found to bind less efficiently than WT CNV. Furthermore, the
      nontransmissible tomato bushy stunt virus did not detectably bind zoospores.
      These binding studies suggest that the specificity of CNV transmission by O.
      bornovanus occurs through specific recognition of a putative zoospore receptor.

PMID- 9234956
TI  - A noncanonical poly(A) signal, UAUAAA, and flanking elements in Epstein-Barr
      virus DNA polymerase mRNA function in cleavage and polyadenylation assays.
AB  - Two forms of the Epstein-Barr virus DNA polymerase (pol) mRNA (3.7 and 5.1 kb)
      have been detected, neither of which contains a canonical poly(A) signal. The 5.1
      kb pol mRNA, which contains a rare poly(A) signal, UAUAAA, studied only in
      transcripts of Hepadnaviridae and a plant pararetrovirus, was analyzed in
      cleavage and polyadenylation assays. Incubation of the pol transcript in cell
      extracts produced relatively low efficiency of cleavage (12 to 14%), which was
      improved by conversion of the poly(A) signal to AAUAAA. Deletion of the UAUAAA
      signal abolished cleavage and polyadenylation. An auxiliary element, UUUGUA, 3-8
      nt upstream of the poly(A) signal and two downstream core elements, a GU-rich
      sequence 36-46 nt, and an AUUUGUGU sequence 47-53 nt downstream of the signal (8
      19 nt and 20-28 nt downstream of cleavage site) facilitated processing of pol
      mRNA. Replacement of sequences near the cleavage/poly(A) site affected cleavage
      accuracy. Binding of the 64-kDa cleavage stimulatory factor to the U-rich as well
      as the GU-rich elements correlated with cleavage efficiency. Thus the UAUAAA
      hexanucleotide plus the other cis-acting elements are clearly functional in the
      native pol mRNA, but are relatively inefficient. Implications of the use of an
      anomalous poly(A) signal and its elements are discussed.

PMID- 9234957
TI  - Geographic distribution and genetic variability of hepatitis delta virus genotype
      I.
AB  - Three genotypes of hepatitis delta virus (HDV) have been identified, each with
      different geographic distributions and disease associations. To better define the
      geographic distribution and genetic variability of HDV genotype I, and to
      evaluate the extent of genome variability in populations with different patterns
      of HDV infection, we have analyzed the sequence of HDV RNA in the sera of 72
      patients from different areas. Patients were primarily residents of the United
      States and areas in and around Greece, including Archangelos, Rhodes. All
      sequences obtained belonged to HDV genotype I, confirming the wide geographic
      distribution of this genotype and its predominance in Europe and the United
      States. In contrast to previous studies, phylogenetic analysis of this large and
      diverse group of sequences, along with all available previously published HDV
      sequences, showed no well-defined subtypes within genotype I. Low sequence
      diversity was found for isolates from the United States, Archangelos, Turkey, and
      Albania, suggesting that HDV was introduced more recently and/or from fewer
      sources into these areas as compared to mainland Greece, Italy, and north Africa,
      where sequence diversity is much greater. The low sequence diversity among
      isolates from Archangelos is particularly interesting in light of the unusually
      mild pattern of HDV disease found in this community. Comparison of nucleic acid
      and amino acid sequences within and among genotypes indicated both highly
      conserved regions as well as genotype-specific sequences that could be related to
      functional differences. The most distinctive of the latter was that corresponding
      to the C-terminal 19-20 amino acids of the long form of hepatitis delta antigen,
      which is highly conserved within each genotype but considerably diverged among
      them.

PMID- 9234958
TI  - Characterization of a processive form of the vaccinia virus DNA polymerase.
AB  - We have previously shown that the purified, 116-kDa DNA polymerase encoded by
      vaccinia virus is inherently distributive, synthesizing only a few nucleotides
      per template binding event under moderate reaction conditions (W. F. McDonald and
      P. Traktman, J. Biol. Chem. 269, 31190-31197). These properties would be
      incompatible with efficient DNA replication in vivo and suggest that the
      polymerase most probably interacts with accessory proteins that stabilize the
      template/polymerase interaction. Here we show that a highly processive form of
      the enzyme is indeed present with cytoplasmic lysates prepared from infected
      cells, and demonstrate that this form of the enzyme is likely to comprise the DNA
      polymerase in association with an early viral protein with a native molecular
      weight of approximately 48K.

PMID- 9234959
TI  - The stress response in fish.
AB  - The stress response in teleost fish shows many similarities to that of the
      terrestrial vertebrates. These concern the principal messengers of the brain
      sympathetic-chromaffin cell axis (equivalent of the brain-sympathetic-adrenal
      medulla axis) and the brain-pituitary-interrenal axis (equivalent of the brain
      pituitary-adrenal axis), as well as their functions, involving stimulation of
      oxygen uptake and transfer, mobilization of energy substrates, reallocation of
      energy away from growth and reproduction, and mainly suppressive effects on
      immune functions. There is also growing evidence for intensive interaction
      between the neuroendocrine system and the immune system in fish. Conspicuous
      differences, however, are present, and these are primarily related to the aquatic
      environment of fishes. For example, stressors increase the permeability of the
      surface epithelia, including the gills, to water and ions, and thus induce
      systemic hydromineral disturbances. High circulating catecholamine levels as well
      as structural damage to the gills and perhaps the skin are prime causal factors.
      This is associated with increased cellular turnover in these organs. In fish,
      cortisol combines glucocorticoid and mineralocorticoid actions, with the latter
      being essential for the restoration of hydromineral homeostasis, in concert with
      hormones such as prolactin (in freshwater) and growth hormone (in seawater).
      Toxic stressors are part of the stress literature in fish more so than in
      mammals. This is mainly related to the fact that fish are exposed to aquatic
      pollutants via the extensive and delicate respiratory surface of the gills and,
      in seawater, also via drinking. The high bioavailability of many chemicals in
      water is an additional factor. Together with the variety of highly sensitive
      perceptive mechanisms in the integument, this may explain why so many pollutants
      evoke an integrated stress response in fish in addition to their toxic effects at
      the cell and tissue levels. Exposure to chemicals may also directly compromise
      the stress response by interfering with specific neuroendocrine control
      mechanisms. Because hydromineral disturbance is inherent to stress in fish,
      external factors such as water pH, mineral composition, and ionic calcium levels
      have a significant impact on stressor intensity. Although the species studied
      comprise a small and nonrepresentative sample of the almost 20,000 known teleost
      species, there are many indications that the stress response is variable and
      flexible in fish, in line with the great diversity of adaptations that enable
      these animals to live in a large variety of aquatic habitats.

PMID- 9234960
TI  - Properties and regulation of the minK potassium channel protein.
AB  - The minK gene encodes a protein of 130 amino acids that has a single
      transmembrane segment and is expressed in many tissues including heart, uterus,
      and kidney. When Xenopus oocytes are injected with minK mRNA, a very slowly
      activating voltage-dependent potassium current is induced in these cells. The
      induced channels appear to result from the interaction of the minK protein with
      other channel-forming subunits such as the KvLQT1 channel. The minK protein is
      intimately associated with the structure of the resultant channels, and mutations
      in minK can alter ion selectivity and modulation by second messengers. Strong
      candidates for native currents regulated by the minK protein include the slow
      component of the cardiac delayed rectifier and potassium currents recorded across
      epithelial cells in vestibular organs and cochlea.

PMID- 9234961
TI  - Effects of milk and milk components on calcium, magnesium, and trace element
      absorption during infancy.
AB  - During early life, infants usually consume a diet that is heavily dominated by
      milk. It is generally believed that breast-fed infants absorb adequate quantities
      of minerals and trace elements, whereas there is some concern about how well
      infants can utilize these nutrients from cow's milk formula and other infant
      diets. Therefore, most infant formulas contain much higher concentrations of
      minerals and trace elements than those of breast milk. Our knowledge of how
      infants can utilize these nutrients from different diets is very limited. This
      paper critically reviews the effects of various components in breast milk, cow's
      milk, and infant formula and how they either facilitate or inhibit the absorption
      of minerals and trace elements. Particular emphasis is put on milk proteins such
      as lactoferrin, casein, and whey proteins, but phytate in soy formula is also
      discussed. Competition among minerals for absorptive pathways as well as other
      nutrient-nutrient interactions are considered in the context of infant nutrition.
      The difficulties involved in assessing mineral and trace element status in
      infants, as well as the potential consequences of suboptimal and excessive
      intakes of calcium, magnesium, iron, zinc, copper, manganese, and selenium are
      also discussed, particularly in the light of infant requirements.

PMID- 9234962
TI  - Actomyosin interaction in striated muscle.
AB  - The mechanics of the actomyosin interaction have been extensively studied using
      the organized filament array of striated muscle. However, the extrapolation of
      these data to the events occurring at the level of a single actomyosin
      interaction has not been simple. Problems arise in part because an active fiber
      has an ensemble of myosin heads that are spread out through the various steps of
      the active cycle, and it is likely that only a small fraction of the heads are
      generating tension at any given time. More recently, two new approaches have
      greatly extended our knowledge of the actomyosin interaction. First, the three
      dimensional crystal structures of both the actin monomer and the myosin head have
      been determined, and these structures have been fit to lower resolution images to
      give atomic models of the actin filament and of the actin filament decorated by
      myosin heads. Second, the technology to measure picoNewton forces and nanometer
      distances has provided direct determinations of the force and step length
      generated by a single myosin molecule interacting with a single actin filament.
      This review synthesizes the existing mechanical data obtained from the more
      organized array of the muscle filament with the results obtained by these two
      technologies.

PMID- 9234963
TI  - Ryanodine receptors of striated muscles: a complex channel capable of multiple
      interactions.
AB  - The ryanodine receptor (RyR) is a high-conductance Ca2+ channel of the
      sarcoplasmic reticulum in muscle and of the endoplasmic reticulum in other cells.
      In striated muscle fibers, RyRs are responsible for the rapid release of Ca2+
      that activates contraction. Ryanodine receptors are complex molecules, with
      unusually large cytoplasmic domains containing numerous binding sites for agents
      that control the state of activity of the channel-forming domain of the molecule.
      Structural considerations indicate that long-range interactions between
      cytoplasmic and intramembrane domains control channel function. Ryanodine
      receptors are located in specialized regions of the SR, where they are
      structurally and functionally associated with other intrinsic proteins and,
      indirectly, also with the luminal Ca2(+)-binding protein calsequestrin.
      Activation of RyRs during the early part of the excitation-contraction coupling
      cascade is initiated by the activity of surface-membrane Ca2+ channels, the
      dihydropyridine receptors (DHPRs). Skeletal and cardiac muscles contain different
      RyR and DHPR isoforms and both contribute to the diversity in cardiac and
      skeletal excitation-contraction coupling mechanisms. The architecture of the
      sarcoplasmic reticulum-surface junctions determines the types of RyR-DHPR
      interactions in the two muscle types.

PMID- 9234964
TI  - Cellular energy utilization and molecular origin of standard metabolic rate in
      mammals.
AB  - The molecular origin of standard metabolic rate and thermogenesis in mammals is
      examined. It is pointed out that there are important differences and distinctions
      between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple
      metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic
      rate, 6) produce heat, and 7) dissipate free energy. The quantitative
      contribution of different cellular reactions to these processes is assessed in
      mammals. We estimate that approximately 90% of mammalian oxygen consumption in
      the standard state is mitochondrial, of which approximately 20% is uncoupled by
      the mitochondrial proton leak and 80% is coupled to ATP synthesis. The
      consequences of the significant contribution of proton leak to standard metabolic
      rate for tissue P-to-O ratio, heat production, and free energy dissipation by
      oxidative phosphorylation and the estimated contribution of ATP-consuming
      processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen
      consumption coupled to ATP synthesis, approximately 25-30% is used by protein
      synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by
      the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with
      mRNA synthesis and substrate cycling also making significant contributions. The
      main cellular reactions that uncouple standard energy metabolism are the Na+, K+,
      H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular
      metabolic rate is controlled by a number of processes including metabolic demand
      and substrate supply. The differences in standard metabolic rate between animals
      of different body mass and phylogeny appear to be due to proportionate changes in
      the whole of energy metabolism. Heat is produced by some reactions and taken up
      by others but is mainly produced by the reactions of mitochondrial respiration,
      oxidative phosphorylation, and proton leak on the inner mitochondrial membrane.
      Free energy is dissipated by all cellular reactions, but the major contributions
      are by the ATP-utilizing reactions and the uncoupling reactions. The functions
      and evolutionary significance of standard metabolic rate are discussed.

PMID- 9234965
TI  - Endocytosis.
AB  - Mammalian cells take up extracellular material by a variety of different
      mechanisms that are collectively termed endocytosis. Endocytic mechanisms serve
      many important cellular functions including the uptake of extracellular
      nutrients, regulation of cell-surface receptor expression, maintenance of cell
      polarity, and antigen presentation. Endocytic pathways are also utilized by
      viruses, toxins, and symbiotic microorganisms to gain entry into cells. One of
      the best-characterized endocytic mechanisms is receptor-mediated endocytosis via
      clathrin-coated pits. This type of endocytosis constitutes the major emphasis of
      this review, with a brief discussion of other endocytic mechanisms and their
      comparison with the receptor-mediated pathway. This review describes and
      evaluates critically current understanding of the mechanisms of entry of plasma
      membrane components such as the receptor-ligand complexes and membrane lipids as
      well as the extracellular fluid into cells. The intracellular sorting and
      trafficking of these molecules upon internalization are also described. The roles
      of endocytosis in physiological and pathological processes are discussed. These
      include maintenance of cell polarization, antigen presentation, glucose
      transport, atherosclerosis, Alzheimer's disease, and the endocytosis of toxins
      and viruses.

PMID- 9234966
TI  - Placental transfer of inorganic ions and water.
AB  - There are great interspecies differences in placental structure as well as in
      permeability properties of the placenta. In all species, however, the placenta
      behaves like a low-permeability barrier containing specific mechanisms of
      transcellular transport for minerals and other substrates for fetal growth and
      metabolism. The minerals that are contained in plasma in low concentrations and
      that are mainly intracellular or sequestered in bones (K+, Mg2+, Ca2+, phosphate)
      are transported to the fetus actively. The transfer of the main extracellular
      ions, Na+ and Cl-, exhibit great interspecies differences. In the sheep, the
      transfer rates of Na+ and Cl- to the fetus are consistent with passive transfer
      mechanisms. In the rat, Na+ is transported to the fetus actively and the transfer
      of Cl- is facilitated by a carrier and/or a channel. Transfer of minerals to the
      fetus is controlled by a variety of mechanisms ranging from very simple ones
      depending on intrinsic properties of the transport systems to complex mechanisms
      of hormonal control. Water is presumed to move across the placenta passively. The
      transfer may be facilitated by the 28-kDa water channel-forming integral protein
      (CHIP28), which is expressed in the trophoblast syncytium.

PMID- 9234967
TI  - Physiology of diving of birds and mammals.
AB  - This review concentrates on the physiological responses, and their control, in
      freely diving birds and mammals that enable them to remain submerged and
      sometimes quite active for extended periods of time. Recent developments in
      technology have provided much detailed information on the behavior of these
      fascinating animals. Unfortunately, the advances in technology have been
      insufficient to enable physiologists to obtain anything like the same level of
      detail on the metabolic rate and physiological adjustments that occur during
      natural diving. This has led to much speculation and calculations based on many
      assumptions concerning usable oxygen stores and metabolic rate during diving, in
      an attempt to explain the observed behavior. Despite their shortcomings, these
      calculations have provided useful insights into the degree of adaptations of
      various species of aquatic birds and mammals. Many of them, e.g., ducks, smaller
      penguins, fur seals, and Weddell seals, seem able to metabolize aerobically, when
      diving, at approximately the same (if not greater) rate as they do at the
      surface. Their enhanced oxygen stores are able to support aerobic metabolism, at
      what would not be considered unusually low levels, for the duration of the dives,
      although there are probably circulatory readjustments to ensure that the oxygen
      stores are managed judiciously. For other species, such as the larger penguins,
      South Georgian shag, and female elephant seals, there is a general consensus that
      they must either be reducing their aerobic metabolic rate when diving, possibly
      by way of regional hypothermia, and/or producing ATP, at least partly, by
      anaerobiosis and metabolizing the lactic acid when at the surface (although this
      is hardly likely in the case of the female elephant seals). Circulation is the
      proximate regulator of metabolism during aerobic diving, and heart rate is the
      best single indicator of circulatory adjustment. During voluntary dives, heart
      rates range from extreme bradycardia to well above resting, reflecting metabolic
      performance. Efferent cardiac control is largely parasympathetic. Reflex
      cardiorespiratory responses are modulated by conditioning and habituation, but
      reflexes predominate during extended dives and during recovery, when gas exchange
      is maximized.

PMID- 9234968
TI  - Stuart Weinstein: advancing the specialty of orthopaedics.

PMID- 9234969
TI  - Were the Hunter brothers wrong? Can surgical treatment repair articular
      cartilage?

PMID- 9234971
TI  - Comparing Mersilene* tape and stainless steel wire as sublaminar spinal fixation
      in the Chagma baboon (Papio ursinus).
AB  - The development of segmental instrumentation has been a major advancement in the
      treatment of spinal problems, but the use of sublaminar stainless steel wire
      (SSW) has not been without untoward effects. This study reports a comparison of
      Mersilene* tape (MT) and stainless steel wire (SSW) used for sublaminar fixation
      in the Chagma baboon (Papio Ursinus). A similar comparative study has not been
      reported, although the local effects of sublaminar SSW in the spinal canal have
      previously been described. The adult Chagma baboon was selected as the
      experimental animal due to its partial upright posture and spinal anatomy,
      similar to that of the human. Six levels of the thoracolumbar spine were
      instrumented with custom designed Harrington hooks and regular one-quarter inch
      threaded rods used as a distraction system. The four intervening laminae were
      fixed to the rods using doubled-over, eighteen gauge sublaminar SSW in six cases
      and five millimeter MT in six cases. Computed axial tomography used to measure
      the AP diameter of the bony spinal canal revealed the AP space occupied by the
      SSW and MT to be 32 percent and 14.8 percent respectively. In the MT group, the
      overlying dura mater was found to be totally intact and revealed no signs of
      abnormal tissue response. A well-formed connective tissue membrane consisting of
      dense connective tissue surrounded the MT and was found to consist of more mature
      fibers than that found in the SSW group. The dura-implant interface was examined
      histologically and a distinct membrane was identified between the dura and the
      superficial aspect of the MT's, as well as intervening between the two MT's.
      Following removal of the MT, in contrast to the SSW, it was apparent that the
      underlying dura was not injured, most probably due to the soft consistency of the
      Mersilene* tape and the well-formed overlying membrane. On clinical grounds the
      fixation in both groups was adequate but the MT group formed a well-circumscribed
      membrane that made removal of the MT easier and potentially safer. The AP space
      occupied by the spinal implant was also found to be less with MT as opposed to
      SSW.

PMID- 9234970
TI  - Fractures of the radius and ulna in adults: an analysis of factors affecting
      outcome.
AB  - Concurrent data were collected by the authors for 104 fractures of the shafts of
      the radius and ulna in 102 adult patients to determine the relationship of
      subjective, objective, radiographic and economic outcome parameters to the method
      of treatment, type of fracture (open or closed), degree of comminution, and the
      presence of other injuries. Patients treated by open reduction and internal
      fixation (ORIF) had less pain, lost less forearm rotation, and returned to the
      same work following injury more frequently than those treated by closed reduction
      and casting (CR) or pins-in-plaster (PIP). The greatest advantages of ORIF over
      other treatment methods were improved skeletal alignment and forearm rotation,
      the factors most often associated with return to the same work following injury.
      Except for a longer time to union and a higher rate of infection, the outcomes of
      open and closed fractures were very similar. The presence of other injuries was a
      strong predictor of a compromised end result, primarily because of more pain,
      greater loss of forearm rotation, and less frequent return to the same work. The
      inclusion of patient satisfaction and work status in the assessment of outcomes
      and the concept of "functional malunion", an outcome-based interpretation of a
      radiographic finding, should help in counselling patients as to the likely
      economic and functional impacts of these injuries.

PMID- 9234972
TI  - The development of orthopaedics in 20th century warfare.

PMID- 9234973
TI  - Bilateral osteofibrous dysplasia: a report of two cases and review of the
      literature.

PMID- 9234974
TI  - Fatality from disseminated intravascular coagulation complicating total hip
      arthroplasty: a case report.
AB  - Following a routine hybrid total hip arthroplasty in an eighty-two year-old
      female, profuse bleeding occurred through the suction drain immediately
      postoperatively. The patient was found to have acute disseminated intravascular
      coagulation. Despite early recognition and treatment the patient died fourteen
      days later.

PMID- 9234975
TI  - Assessing the accuracy of a prototype drill guide for fibular graft placement in
      femoral head necrosis.
AB  - A prototype drill guide was developed to improve the accuracy of surgical
      placement of fibular grafts for the treatment of femoral head necrosis. To
      document performance, two tantalum beads, one placed on the lateral femoral shaft
      and the other embedded in the superior portion of the head, were used to define
      the desired graft tract in a series of seven surrogate femurs. Two orthogonal x
      rays of the drill guide mounted on each surrogate femur were taken both before
      and after drilling. After stylus digitization of each x-ray pair, a computer
      program calculated the achieved accuracy of the drill. The mean of the absolute
      error between the desired versus obtained position of the drill tip was 3.68 mm
      (s.d. 1.24 mm), and the random component of the error was 1.98 mm (s.d. 0.89 mm).

PMID- 9234976
TI  - The effects of time and light exposure on contact and pressure measurements using
      Fuji prescale film.
AB  - The search for methods to demonstrate and accurately measure contact area and
      pressure within human joints has been and remains an active one. Presenssor is a
      measuring system developed by Fuji Photo Film Co., Ltd. and used in medical
      applications. The color intensity fades with time and exposure to light. These
      changes have not been well documented despite the increasing use of Fuji film in
      biomedical research. These changes in color intensity provide a source of error
      in the calculated measurements. The known variability of the color density of
      film exposed to light and air can be measured and predicted. Methods to control
      and improve the accuracy and reliability of study data are suggested. Film was
      exposed to three different amounts of pressure and placed into one of four
      subgroups: exposed to light and taped or not taped, and stored in the dark and
      taped or not taped. Fading of the color density was seen after only a few hours
      of exposure to light when the film was left untaped. When the film was taped, a
      slight darkening was seen. For the best accuracy and reliability, the film should
      be digitized or analyzed within eight hours of exposure to pressure.

PMID- 9234977
TI  - Diagnostic clarity in orthopedics due to advanced technology: thoughts on the
      surgeon's role and responsibilities.

PMID- 9234978
TI  - Does participation in sports cause osteoarthritis?

PMID- 9234979
TI  - Septic arthritis caused by chronic osteomyelitis.
AB  - We have treated four cases of previously quiescent osteomyelitis which presented
      as septic arthritis in an adjacent joint. The osteomyelitic focus was in the bone
      proximal to the involved joints (zero to ten centimeters above the joint line).
      Based on the presenting history, physical findings, laboratory tests and cultures
      of joint fluids, the joint sepsis was low grade in all patients which led to
      delays in diagnosis and treatment. Aggressive surgical debridement of both bone
      and joint, followed by a prolonged course of antibiotics led to resolution in all
      patients. A high index of suspicion combined with adequate radiographs of the
      surrounding bones should lead to the appropriate diagnosis and treatment.

PMID- 9234980
TI  - Limb lengthening in Turner syndrome.
AB  - We report the results and complications of eight consecutive patients who
      underwent bilateral tibial lengthenings for dwarfism associated with Turner
      syndrome. Lengthening was performed via distraction osteogenesis with monolateral
      external fixation. Tibias were lengthened an average distance of 9.2 centimeters
      or 33 percent of the original tibial length. The average total treatment time was
      268 days. The overall complication rate was 169 percent for each tibia lengthened
      and each segment required an average of 1.7 additional procedures. Seven cases
      (44 percent) required Achilles tendon lengthening and nine cases (56 percent)
      developed angulation before or after fixator removal; six of these segments
      required corrective osteotomy for axial malalignment. Two cases (12.5 percent)
      developed distraction site nonunion and required plating and bone grafting. From
      this series we conclude that tibial lengthening via distraction osteogenesis can
      be used to treat disproportionate short stature in patients with Turner syndrome.
      However, the benefit of a cosmetic increase in height may not compensate for the
      high complication rate. Efforts to determine the psychosocial and functional
      benefits of limb lengthening in patients with short stature is necessary to
      determine the true cost-benefit ratio of this procedure.

PMID- 9234981
TI  - Decrease in fibronectin occurs coincident with the increased expression of its
      integrin receptor alpha5beta1 in stress-deprived ligaments.
AB  - Stress deprivation secondary to immobilization leads to atrophic changes in
      periarticular soft tissues. The changes in ligaments include a disorganization of
      collagen and cellular ultrastructure with varied biochemical alterations
      resulting in a functionally weaker tissue. This study tests the hypothesis that
      alterations in fibronectin (Fn) and the expression of its integrin receptor
      alpha5beta1 in ligament fibroblasts accompany the extracellular matrix remodeling
      which occurs in stress-deprived knee ligaments. The left knees of eighteen New
      Zealand white rabbits were surgically immobilized in acute flexion. Fibroblasts
      within three nine week and three twelve week stress-deprived anterior cruciate
      ligaments (ACLs) and medial collateral ligaments (MCLs) demonstrated markedly
      increased immunostaining for the beta1 and alpha5 integrin subunits, as compared
      to fibroblasts in the contralateral unoperated control ligaments. The effects of
      stress deprivation on the concentration of Fn was measured by competitive ELISA
      on the remaining twelve rabbits. Decreases in Fn of 54.0 percent and 63.7 percent
      occurred in the ACL after nine and twelve weeks of stress deprivation when
      compared to contralateral controls. The MCL had less of a decrease, losing 37.7
      percent and 41.7 percent at nine and twelve weeks, respectively. These results
      suggest an important role for the Fn-specific integrin receptor alpha5beta1 in
      remodeling stress-deprived periarticular ligamentous tissue, and the importance
      of maintaining normal stresses on periarticular ligaments to prevent the
      degradation of extracellular matrix components such as Fn.

PMID- 9234982
TI  - Pelvic fractures and mortality.
AB  - A retrospective study of all patients (N = 343) with pelvic fractures admitted to
      our trauma service was conducted to evaluate the impact of pelvic fractures on
      mortality. All patients sustained additional injuries with an average Injury
      Severity Score (ISS) of twenty. Thirty-six patients died. This group had more
      severe pelvic fractures as graded by the Tile classification as well as a greater
      number and severity of associated injuries. Six patients died as a direct result
      of pelvic hemorrhage. In six other patients, pelvic fractures contributed to
      their demise. The other twenty-four patients died from brain injury, thoracic
      hemorrhage, or other non-pelvic causes. Overall mortality for patients with
      pelvic fractures was 10.5 percent This was a 1.4 fold increase in mortality
      compared to other trauma patients during the same time period without pelvic
      fractures. Mortality was dramatically increased in patients over sixty years of
      age (37 percent mortality compared to 8 percent). This greater than four-fold
      increase in deaths in the elderly appears to be an age related effect because the
      elderly patients generally had a lower ISS and less severe pelvic trauma than
      younger patients. We conclude that sustaining a pelvic fracture places the
      patient at an increased risk of death. Pelvic fractures contributed directly to
      death in one-third of the mortalities, one-third died from complications
      associated with pelvic fractures, and one-third died from other causes.

PMID- 9234983
TI  - New advances in the molecular biology of musculoskeletal neoplasms.

PMID- 9234984
TI  - Long term follow-up of medial column fusion and tibialis anterior transposition
      for adolescent flatfoot deformity.
AB  - We report the results of three patients (four feet) who had surgical correction
      of adolescent flatfeet performed over fifty years ago. The surgery involved
      medial column stabilization with fusion procedures and tibialis anterior
      transposition into the navicular (Young's tenosuspension procedure). In this
      small sample, we found a high rate of painful arthrosis that developed over time
      in the contiguous joints of the foot.

PMID- 9234985
TI  - Total joint replacement: on innovation, ambition, courage, irony and morsellized
      bone, of course.

PMID- 9234986
TI  - Detection of wire EMG activity in whiplash injuries using wavelets.

PMID- 9234987
TI  - Selecting topics for scientific investigation.

PMID- 9234988
TI  - Use of anchor sutures to repair labral avulsions of the hip: a brief report.

PMID- 9234989
TI  - Pigmented villonodular synovitis arising from the subtalar joint: a case report.

PMID- 9234990
TI  - Hereditary disorders with maladies of the wrist and elbow.

PMID- 9234991
TI  - "Teflon-coated peptides": hexafluoroacetone trihydrate as a structure stabilizer
      for peptides.

PMID- 9234992
TI  - Pressure-jump relaxation kinetics of a DNA triplex helix-coil equilibrium.

PMID- 9234993
TI  - Imaging of individual biopolymers and supramolecular assemblies using noncontact
      atomic force microscopy.
AB  - A variety of biopolymers is imaged using noncontact atomic force microscopy.
      Samples are prepared by aerosol spray deposition of aqueous solutions on freshly
      cleaved mica followed by air drying. The distributions of contour lengths and
      chain or fibril thicknesses normal to the mica substrate can be measured for
      individual polymer molecules or molecular assemblies. In many cases it is
      possible to conclude that the structures imaged and quantitatively analyzed are
      representative of those present in solution and not artifacts of the
      deposition/dessication process. Imaging of linear and cyclic triple helices of
      the polysaccharide scleroglucan is demonstrated. Measurements of the triple helix
      thickness normal to the mica surface are analyzed, and successful measurements of
      the molecular weight distribution and mean molar mass are described. It is
      demonstrated that the extent of chain association in the polysaccharide xanthan
      can be modulated by the addition of low molecular weight salts. The contour
      length and chain thickness distributions in a xanthan fraction are presented.
      Increases in the extent of chain association with increasing polymer
      concentration are documented for the gelling polysaccharide gellan, and the
      formation of stiff fibrillar gellan aggregates in the presence of added low
      molecular salt is demonstrated. Images are presented of the polysaccharide kappa
      carrageenan in its disordered, and presumably single-stranded, state. Biopolymers
      other than polysaccharides can be imaged by the same technique; this is
      demonstrated with the fibrous protein collagen. In general it is shown that
      aerosol spray deposition of biopolymer samples can be used in conjunction with
      noncontact atomic force microscopy to provide a fast, reliable, and reproducible
      method for assessing the size and shape distributions of individual biological
      macromolecules and macromolecular assemblies in solution with a minimum of time
      and effort devoted to sample preparation.

PMID- 9234994
TI  - Aggregation and conformational transition in aqueous solution of a bombolitin III
      analogue containing a photoreactive side-chain group.
AB  - The peptide toxin bombolitin III [B(III)], originally isolated from bumblebee
      venom, has been shown to undergo a concentration-dependent conformational change
      from a random structure to an alpha-helix induced by aggregation. The aggregation
      process and the consequent folding results from a delicate balance of
      electrostatic and hydrophobic interactions. The conformational change is strongly
      dependent on pH and salt concentration. In order to gain insight on the structure
      of the aggregates, and in particular, on the aggregation number and relative
      orientation of helices in the molecular complexes, the following analogue of
      bombolitin III was designed and synthesized: Ile-Lys-Bpa-Met-Asp-Ile-Leu-Ala-Lys
      Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 Bpa3-B(III) where Bpa is
      benzoylphenylalanine. Bpa3-B(III) aggregates were investigated by CD and nmr
      techniques. The observed nuclear Overhauser effect pattern accounts for an
      antiparallel orientation of two distinct helices. The Bpa side chain allows for
      the photoinduced cross reaction with any aliphatic proton in spatial proximity.
      After irradiation, the reaction mixture was analyzed by high performance liquid
      chromatography and electrospray mass spectrometry. The results confirmed the
      presence of dimeric and trimeric complexes of bombolitin III formed upon
      interhelix cross-linking.

PMID- 9234995
TI  - Molecular modeling of c-erbB2 receptor dimerization: coiled-coil structure of
      wild and oncogenic transmembrane domains--stabilization by interhelical hydrogen
      bonds in the oncogenic form.
AB  - Dimerization models of c-erbB2 transmembrane domains (Leu651-Ile675) are studied
      by molecular mechanics and molecular dynamics simulations. Both wild and Glu
      mutated transmembrane helices exhibit the same relative orientation for favorable
      associations and dimerize preferentially in left-handed coiled-coil structures.
      The mutation point 659 belongs to the interfacing residues, and in the
      transforming domain, symmetric hydrogen bonds between Glu carboxylic groups
      stabilize the dimeric structure. The same helix packing found for the wild
      dimers, except side-chain-side-chain hydrogen bonds, suggests that the
      transmembrane domains dimerize according to similar process. Structural and
      energetical characterization of the models are presented.

PMID- 9234997
TI  - Electrophoresis of proteins in semidilute polyethylene glycol solutions:
      mechanism of retardation.
AB  - The retardation of proteins in the M(r) range of 15-500 kDa in capillary
      electrophoresis conducted in semidilute solutions of the polymer polyethylene
      glycol (M(r) range 0.2-8.0 X 10(6)), was measured. The purpose was to test the
      predictions of the scaling theory with regard to the relation of retardation to
      (a) the M(r) of the polymer, (b) the concentration of the polymer, and (c) the
      radius of the protein particles. These predictions derive from a mechanism that
      relates retardation to the screening length of the polymer solution, viewed as
      the average distance between the entanglement points of polymer chains. For the
      molecular weight range from 60 to 500 kDa of (near) spherical proteins, the
      retardation was found to be related to polymer concentration c as mu/mu(0) = exp(
      Ac0.69) where mu/mu(0) is the retardation expressed as the ratio between the
      mobility in polymer solution and that in free solution. The value of the exponent
      of 0.69 is in close agreement with the value of 0.75 predicted by the scaling
      theory. Parameter A was found (a) to scale as the 0.04th power of M(r) (polymer),
      approximating the predicted value of 0; and (b) to be proportional to particle
      radius as predicted. All measured values of retardation were independent of
      electric field strength in the range of 37-370 V/cm. Thus, experimental findings
      are consistent with the mechanism relating electrophoretic retardation to the
      screening length of the polymer network in the specified molecular weight range
      of proteins. Under the same conditions, log(mu/mu(0)) of proteins with M(r)'s
      less than 60 kDa (a) scales as the -0.06th power of M(r) (polymer), and (b) is
      proportional to polymer concentration, suggesting a retardation mechanism that is
      not related to the screening length.

PMID- 9234996
TI  - Binding of basic amphipathic peptides to neutral phospholipid membranes: a
      thermodynamic study applied to dansyl-labeled melittin and substance P analogues.
AB  - A thermodynamic approach is proposed to quantitatively analyze the binding
      isotherms of peptides to model membranes as a function of one adjustable
      parameter, the actual peptide charge in solution z(p)+. The main features of this
      approach are a theoretical expression for the partition coefficient calculated
      from the molar free energies of the peptide in the aqueous and lipid phases, an
      equation proposed by S. Stankowski [(1991) Biophysical Journal, Vol. 60, p. 341]
      to evaluate the activity coefficient of the peptide in the lipid phase, and the
      Debye-Huckel equation that quantifies the activity coefficient of the peptide in
      the aqueous phase. To assess the validity of this approach we have studied, by
      means of steady-state fluorescence spectroscopy, the interaction of basic
      amphipathic peptides such as melittin and its dansylcadaverine analogue (DNC
      melittin), as well as a new fluorescent analogue of substance P, SP (DNC-SP) with
      neutral phospholipid membranes. A consistent quantitative analysis of each
      binding curve was achieved. The z(p)+ values obtained were always found to be
      lower than the physical charge of the peptide. These z(p)+ values can be
      rationalized by considering that the peptide charged groups are strongly
      associated with counterions in buffer solution at a given ionic strength. The
      partition coefficients theoretically derived using the z(p)+ values were in
      agreement with those deduced from the Gouy-Chapman formalism. Ultimately, from
      the z(p)+ values the molar free energies for the free and lipid-bound states of
      the peptides have been calculated.

PMID- 9234998
TI  - Comparison of van der Waals and semiempirical calculations of the molecular
      volumes of small molecules and proteins.
AB  - Molecular volumes for hydrocarbons, amino acids, peptides, and 14 globular
      proteins were calculated by techniques using van der Waals radii and by
      semiempirical molecular orbital methods. The resulting values were compared to
      experimentally determined volumes. The values obtained by methods employing van
      der Waals radii were found to be up to three times smaller than the
      experimentally determined values in the case of proteins, 25% smaller than the
      experimental values for peptides, and up to 50% greater than experimental values
      for simple hydrocarbons. For the semiempirical calculations, neither the type nor
      precision of the calculation altered the percentage of the electron density
      required to reproduce the experimentally observed volumes for any of the
      different types of molecules tested. For molecules en vacuo, the amount of
      electron density included was approximately 98.5% of the total calculated value.
      For solvated molecules, the percentage was closer to 99.5%. From the results of
      our studies, we conclude that semiempirical techniques are more reliable, less
      arbitrary, and hence are more accurate for the determination of molecular
      volumes. The methods by which we employ semiempirical techniques for
      determination of molecular volume will be described in detail.

PMID- 9235000
TI  - Fluorescence characterization of type I collagen from normal and silicotic rats
      and its quenching dynamics induced by hypocrellin B.
AB  - In this paper, we studied the quenching mechanism of intrinsic fluorescence of
      type I collagen by a new type photosensitizer and fluorescence quencher,
      hypocrellin B (HB). It was indicated that type I collagen can emit Tyr-intrinsic
      fluorescence with the excitation wavelength of Tyr (lambda(ex) = 269 nm). Its
      fluorescence decay conform to the triexponential rule of the fluorescence
      lifetime. The intrinsic fluorescence of type I collagen can be effectively
      quenched by HB through a process of charge and energy transference, which is
      involved in the collisional quenching, the dipolar inducement, and the formation
      of exciplex between HB and excited fluorophores of collagen. The fluorescence
      quenching would be weakened by higher ionic environments. The fluorescence
      emission and its quenching rate of abnormal silicotic collagen show falling
      trends, implying its much weakened potential of charge and energy transference,
      and its lessen bioelectric activities. In conclusion, the bioelectric properties
      of collagen depends on the perfect order of its molecular structure and orderly
      intramolecular and intermolecular interactions, which is important in its
      performing normal physiological functions. It is also demonstrated that the
      fluorescence quenching technique, using HB as a quencher, is truly an effectively
      method for biomolecular studies.

PMID- 9234999
TI  - Interactions of DNA with a new electron-deficient tentacle porphyrin: meso
      tetrakis[2,3,5,6-tetrafluoro-4-(2-t rimethylammoniumethyl-amine)phenyl]porphy
      rin.
AB  - A new electron-deficient tentacle porphyrin meso-tetrakis[2,3,5,6-tetrafluoro-4
      (2-trimethylammoniumethylamine )phenyl]porphyrin (TthetaF4TAP) has been
      synthesized. The binding interactions of TthetaF4TAP with DNA polymers were
      studied for comparison to those of an electron-deficient tentacle porphyrin and
      an electron-rich tentacle porphyrin; these previously studied porphyrins bind to
      DNA primarily by intercalative and outside-binding modes, respectively. The three
      tentacle porphyrins have similar size and shape. The basicity of TthetaF4TAP
      indicated that it has electronic characteristics similar to those of the
      intercalating electron-deficient tentacle porphyrin. However, TthetaF4TAP binds
      to calf thymus DNA, [poly(dA-dT)]2, and [poly(dG-dC)]2 in a self-stacking,
      outside-binding manner under all conditions. Evidence for this binding mode
      included a significant hypochromicity of the Soret band, a conservative induced
      CD spectrum, and the absence of an increase in DNA solution viscosity. As found
      previously for the electron-rich porphyrin, the results suggest that combinations
      of closely related self-stacked forms coexist. The mix of forms depended on the
      DNA and the solution conditions. There are probably differences in the detailed
      features of the self-stacking adducts for the two types of tentacle porphyrins,
      especially at high R (ratio of porphyrin to DNA). At low R values, the induced CD
      signal of TthetaF4TAP/CT DNA resembled that of TthetaF4TAP/[poly(dA-dT)]2,
      suggesting that TthetaF4TAP binds preferentially at AT regions. Competitive
      binding experiments gave evidence that TthetaF4TAP binds preferentially to
      [poly(dA-dT)]2 over [poly (dG-dC)]2. Thus, despite the long, positively charged,
      flexible substituents on the porphyrin, the binding of TthetaF4TAP is
      significantly affected by base-pair composition. Similar characteristics were
      found previously for the electron-rich tentacle porphyrin. Thus, significant
      changes in electron richness have relatively minor effects on this outside
      binding selectivity for AT regions. TthetaF4TAP is the first porphyrin with
      electron deficiency and shape similar to intercalating porphyrins that does not
      appear to intercalate. All porphyrins reported to intercalate have had pyridinium
      substituents. Thus, the electronic distribution in the porphyrin ring, not just
      the overall electron richness, may play a role in facilitating intercalation.

PMID- 9235001
TI  - Qualitative and quantitative analysis of the secondary structure of cytochrome C
      Langmuir-Blodgett films.
AB  - A qualitative and quantitative analysis of the conformation of Langmuir-Blodgett
      (LB) dried films of cytochrome C on silicon wafers was performed by Fourier
      transform ir (FTIR) spectroscopy. A deconvolution procedure was applied to the
      amide I band analysis, in order to determine the percentage of the different
      secondary structures. Qualitative analysis was performed by examining difference
      spectra. Films obtained by spreading protein solutions at pH 7.4 and 1, dried at
      25 and 100 degrees C, on silicon wafers were also examined in order to detect
      spectral components associated with denatured protein domains, and to compare
      them with cytochrome C LB films. FTIR spectroscopy showed that the following
      important changes characterise LB film spectra: (a) the alpha-helix component is
      higher (its percentage is 57 and 54%) than the one estimated in dried film
      obtained by spreading the solutions at pH 7.4 on a silicon substrate (43%), (b)
      there is an increase in the intensity of bands attributed to protonated carboxy
      group bands, involved and not involved in the formation of hydrogen bonds, and a
      decrease in those attributed to deprotonated carboxy groups, (c) the intensity of
      several bands attributed to aromatic amino acids and aliphatic chains increases,
      and (d) bands due to O-H stretching vibrations of crystallization water are
      present. These conformational changes could be induced by protein-protein
      interaction caused by the close packing of molecules that occurs during LB film
      formation; it cannot be excluded that they may be accompanied by partial changes
      in the tertiary structure of the protein. A preferential orientation of protein
      molecules in LB films is also a possibility.

PMID- 9235002
TI  - Thermodynamic model of secondary structure for alpha-helical peptides and
      proteins.
AB  - A thermodynamic model describing formation of alpha-helices by peptides and
      proteins in the absence of specific tertiary interactions has been developed. The
      model combines free energy terms defining alpha-helix stability in aqueous
      solution and terms describing immersion of every helix or fragment of coil into a
      micelle or a nonpolar droplet created by the rest of protein to calculate
      averaged or lowest energy partitioning of the peptide chain into helical and coil
      fragments. The alpha-helix energy in water was calculated with parameters derived
      from peptide substitution and protein engineering data and using estimates of
      nonpolar contact areas between side chains. The energy of nonspecific hydrophobic
      interactions was estimated considering each alpha-helix or fragment of coil as
      freely floating in the spherical micelle or droplet, and using water/cyclohexane
      (for micelles) or adjustable (for proteins) side-chain transfer energies. The
      model was verified for 96 and 36 peptides studied by 1H-nmr spectroscopy in
      aqueous solution and in the presence of micelles, respectively ([set 1] and [set
      2]) and for 30 mostly alpha-helical globular proteins ([set 3]). For peptides,
      the experimental helix locations were identified from the published medium-range
      nuclear Overhauser effects detected by 1H-nmr spectroscopy. For sets 1, 2, and 3,
      respectively, 93, 100, and 97% of helices were identified with average errors in
      calculation of helix boundaries of 1.3, 2.0, and 4.1 residues per helix and an
      average percentage of correctly calculated helix-coil states of 93, 89, and 81%,
      respectively. Analysis of adjustable parameters of the model (the entropy and
      enthalpy of the helix-coil transition, the transfer energy of the helix backbone,
      and parameters of the bound coil), determined by minimization of the average
      helix boundary deviation for each set of peptides or proteins, demonstrates that,
      unlike micelles, the interior of the effective protein droplet has solubility
      characteristics different from that for cyclohexane, does not bind fragments of
      coil, and lacks interfacial area.

PMID- 9235004
TI  - [Prolongation of fentanyl-induced decreased arousal by clonidine].
AB  - Both fentanyl and clonidine lead to a reduction of vigilance. We tested the
      influence of clonidine on a fentanyl induced change of vigilance using a cross
      out concentration test (b-cross-out test). With local ethics committee approval,
      we conducted a randomised double-blinded cross-over study with 10 healthy male
      subjects (25-35 years old). Each volunteer received intravenously at two separate
      sessions 1.5 micrograms/kg fentanyl and 1.5 micrograms/kg fentanyl plus 3
      micrograms/kg clonidine. For testing the level of vigilance a concentration test
      (b-cross-out) was used. The number of correctly revised marks was evaluated prior
      to drug administration (TI), directly after application, one hour later and two
      hours later. Our data underwent a multiple analysis of variance. With fentanyl
      two hours after application the mean increase of correctly revised marks was 12%
      when compared to those prior to application (p < 0.024). This means that with
      fentanyl a learning effect was achieved as described in the literature. With
      fentanyl and clonidine two hours after application, a decrease in vigilance of 7
      1/4 in comparison with TI was seen (n.s.). This reduction of vigilance should be
      considered during the postoperative course and especially with regard to ambulant
      anaesthesia when using clonidine.

PMID- 9235003
TI  - [Diagnosis of disposition for malignant hyperthermia--an updated review based on
      1,001 studies].
AB  - The in vitro contracture test (IVCT) based on European Malignant Hyperpyrexia
      Group criteria including the linked quality guarantee is carried out in 6 centres
      in Germany. Due to the genetic heterogeneity of malignant hyperthermia. This test
      remains the existing standard, despite intensive search for less invasive
      diagnostic methods. The test is necessary for clarification of narcosis incidents
      and diagnosis of individual disposition of MH-afflicted families. The analysis of
      11 years of experience with 1.001 investigations in the Leipzig centre focuses on
      characteristic problems. It indicates, that severe courses with resulting
      fatality (37 cases in the whole observation period in the centre district had a
      decreasing tendency. Independently thereof the rate of demands for diagnostics
      remains constant at 125 per year. Apparently MH related incidents are under
      better control now. Of the requested diagnostics 85% are related to anaesthesia
      incidents, 15% to other MH related problems [myopathies, unexplained fever
      attacks]. Of the patients tested 59.7% were MH-negative (MHN), 33.7% MH-positive
      (MHS) and 6.3% were equivocally positive (MHE). A parallel part of the study
      regarding IVCT and histology/morphometry in 230 consecutive examinations did not
      show any correlation. Ultrastructural investigations accordingly are carried out
      only if there is suspicion of myopathy. Differentiation of the in vitro threshold
      values shows a relation to the patients' risks. Low threshold values were
      detected in persons diagnosed as MHS from families with MH related deaths: one
      man diagnosed MHS died from an anaesthesia-unrelated MH crisis. In a parallel
      test of MH-positive muscles with new inhalational narcotics (sevoflurane,
      desflurane), a strong correlation to triggering of contracture by halothane was
      detected. In contrast, no information about a false negative result exists at
      this time. MH manifestation was observed postoperatively only in one patient 1337
      patients MHS, 63 MHE). However, in 3 cases cardio-circulatory arrests occurred
      under local anaesthesia without further consequences. The analysis documents the
      safety of IVCT and the clarity of its results. IVCT is the base for an improved
      communication with patients and colleagues.

PMID- 9235005
TI  - [Drug onset time of atracurium after pancuronium priming in elderly patients].
AB  - Synergism occurs between some combinations of non-depolarising muscle relaxants.
      To test the effect of pancuronium as a priming dose of atracurium, 45 adults were
      anaesthetised with 25 micrograms/kg alfentanil. 75 micrograms/kg midazolam, and
      0.25 mg/kg edomidate, O2/N2O and enflurane, and were randomised to one of three
      groups. After induction, 15 patients received 0.5 mg/kg atracurium, 15 were
      primed with 0.075 mg/kg atracurium and another 15 with 0.0125 mg/kg pancuronium
      and three minutes later 0.45 mg/kg atracurium. Neuromuscular response was
      monitored by adductor pollicis electromyogram (EMG) by stimulating in a TOF
      pattern. Times for tI reduction of 75, 50, 25 and 0% and tI recovery to 10% were
      taken. There were no differences between the two groups that received only
      atracurium. The pancuronium priming group showed a significantly faster onset of
      neuromuscular blockade (tI = 0%: control group I: 76.3 +/- 15.4 sec vs.
      pancuronium group III: 64.3 +/- 11.3 sec) and a prolonged recovery. Pancuronium
      priming can shorten the onset time of atracurium while atracurium priming alone
      showed no shortening. This suggests a synergism for pancuronium priming in
      combination with atracurium.

PMID- 9235007
TI  - Bibliography. Current world literature. Lymphocyte activation and effector
      functions.

PMID- 9235006
TI  - [Serum cytokines and cytokine receptors in children after small or larger
      surgical interventions with halothane anesthesia].
AB  - Immune dysfunction or immune defect syndrome can result postoperatively. It is
      not yet clear what part is played by the operative trauma itself or by narcotics.
      To answer this question, 54 patients (ASA 1) aged between 4 and 16 were examined.
      In group I there were 28 patients with minor operations and in group II 26
      patients with moderate ones. We chose halothan, N2O and O2 for inhalational
      anaesthesia for all patients, IL-6. TNF alpha, IL-IRA, IL-2R and sTNF-RII
      measuring times were preoperative directly postoperative and on the first and
      third postoperative days. In contrast to TNF-alpha, IL-6 showed itself in both
      groups to be an "early" immune parameter with trauma-related kinetics. IL-IRA
      increased in both groups with significant values on the first postoperative day.
      Trauma-related differences between the groups were apparent. sIL-2R was less
      pronounced, IL-6 and IL-IRA parameters proved to be sensitive indicators of
      operative trauma intensity. The differing IL-IRA kinetic after minor or moderate
      trauma indicates that narcotic effects may be manifested at cytokine receptor
      level. Monitoring of the presented parameters on the first and third
      postoperative days together with base data appears to be appropriate for
      determining perioperative immune reaction.

PMID- 9235008
TI  - Primary care for persons with disabilities. Proceedings of The Primary Care
      Summit. Detroit, Michigan, April 6, 1995.

PMID- 9235009
TI  - [Angelo Mosso: a scientist mounting 2 centuries].

PMID- 9235010
TI  - [Laws, principles, and theory of natural sciences].

PMID- 9235011
TI  - [Seroepidemiological survey on diphtheria and tetanus immunization coverage in
      adolescents in Calabria].

PMID- 9235012
TI  - [Prevalence of hepatitis A virus antibodies in food handlers].

PMID- 9235013
TI  - [Salmonellosis in the territory of the Local Health Unit of Imola. An
      epidemiological study of notified cases in 1976-1993].

PMID- 9235014
TI  - [Evaluation of glucose tolerance test in a group of young athletes with diabetes
      in the family].

PMID- 9235015
TI  - [Measurement of microbial air pollution: cfu/m3 A.M.I. (Air Microbial Index). 2].

PMID- 9235016
TI  - [Presence and diffusion of Vibrio cholerae in aquatic environment].

PMID- 9235017
TI  - [Enteric viruses in sludge at the domestic waste treatment plants].

PMID- 9235018
TI  - Effect of bovine serum, hyaluronic acid and netilmicine on the in vitro adhesion
      of bacteria isolated from human-worn disposable soft contact lenses.

PMID- 9235019
TI  - [A proposal for reorientation of SMB (Servizi di Medicina di Base):
      simplification of bureaucracy and epidemiological work].

PMID- 9235020
TI  - [Strategic management in health services].

PMID- 9235021
TI  - [Health care services tariffs, QA and new technologies].

PMID- 9235022
TI  - [Levodopa: controlled release or standard?].

PMID- 9235024
TI  - [A new variant of Creutzfeldt-Jakob disease].

PMID- 9235023
TI  - [The effect of controlled release of DOPA and carbidopa on clinical response and
      plasma pharmacokinetics of DOPA in parkinsonian patients].
AB  - This is a multicentric double blind comparison of the effects of standard and
      slow release levodopa + carbidopa formulations in patients with Parkinson's
      disease. Sixty four patients with simple fluctuations were included and 43
      finished the study. The study had three phases: a) optimal dose findings phase
      with standard levodopa + carbidopa; b) open label, cross over study with the two
      formulations, and c) double blind, parallel investigation. The following results
      were obtained. There was not a difference in the severity of disability according
      to UPDRS, part 3, scores though the subjective impressions of patients were in
      favor of standard formulations. The Sustained release levodopa + carbidopa
      produced significant improvement of dystonia in off period, pain due to akinesia
      in off and the number of hours in off and the quality and latency of sleep. In
      addition there was a tendency in favor of slow release compounds for early
      morning akinesia, global effect and impression of the examining physician. Low
      protein diet improved the kinetics of levodopa and the clinical response with
      both formulations. The clinical usefulness of standard and slow release levodopa
      + carbidopa formulation should be weighted according to individual problems of
      patients with Parkinson's disease.

PMID- 9235025
TI  - [Exophthalmos and cranial neuropathy as a form of presentation of Wegener's
      granulomatosis].
AB  - The cases of three patients with Wegener's granulomatosis presenting as
      exophthalmos and cranial neuropathy are reported. In the first patient's symptoms
      were secondary to the presence of a retro-orbital mass. In the second and third
      patients there was dissemination of neighboring granulomatous processes.
      Paranasal sinuses were involved in two patients, but clinical manifestations were
      evident in only one. Full remission was achieved in all three. Two patients had
      been received immunosuppressant therapy for inflammatory processes evaluated a
      posteriori in the context of Wegener's granulomatosis. The immunosuppressant
      treatment seems to have conditioned this unusual clinical presentation.

PMID- 9235026
TI  - [Miller-Fisher syndrome associated with toxoplasmosis].
AB  - We report on an immunocompetent patient who developed acquired toxoplasmosis and
      Miller-Fisher syndrome with central and peripheral neural involvement. We suggest
      the possible relationship between acquired toxoplasmosis and Miller-Fisher
      syndrome, even though we cannot exclude a mere coincidence. To our knowledge such
      an association has not been reported.

PMID- 9235027
TI  - [On the provision of teaching positions in Spanish universities. Letter].

PMID- 9235028
TI  - [Early corticoid treatment of idiopathic facial palsy (Bell)].
AB  - Idiopathic facial palsy (IFP) (Bell's palsy) is the commonest cause of acute
      facial paralysis. Perhaps because of its unknown origin, a wide range of
      treatments are used. Controversy exists as to whether the disorder should be left
      to run its natural course or treated with steroids. The effect of early steroid
      treatment on the evolution of IFP was evaluated in the Ear, Nose, and Throat
      Service of the University Hospital of Alicante (Spain) with a prospective
      protocol from September 1991 to January 1992. The therapeutic protocol for all
      patients (47 patients) was an intramuscular injection of 60 mg prednisone in the
      Emergency Room followed by a course of oral steroids (deflazacort) that was
      gradually tape-red-off. The average duration of IFP before presentation in the
      Emergency Department was 1.30.9 days. Clinical improvement was observed on day
      149 and a complete cure by day 3026. Full recovery of facial motor function
      without sequelae occurred in 95.6% of patients. Age, the intensity of paralysis,
      and a history of hypertension and diabetes had a negative influence on the course
      of IFP. These results support early steroid treatment for IFP.

PMID- 9235029
TI  - [Relation between the Toynbee phenomenon and tube dysfunction].
AB  - The effect of the Toynbee phenomenon in patients with nasal packing was studied.
      Nasal packing was used in 35 patients admitted for surgical correction of septal
      deviation. Middle ear pressure was measured during nasal packing and the results
      were compared with nasopharyngeal pressure gradients recorded during the Toynbee
      maneuver. The aim of the study was to demonstrate that one of the main causes of
      tube dysfunction during nasal obstruction is the Toynbee phenomenon.

PMID- 9235030
TI  - [Primary nasal sinus malignant melanomas].
AB  - Primary malignant melanoma of the mucosa of the nasal and paranasal sinuses is
      rare, difficult to treat, and usually has a poor prognosis. Seven cases, six
      women and one man (mean age 76.5 years), were treated at the Hospital 12 de
      Octubre (Madrid, Spain) during the period 1982-1994. The presenting symptoms,
      diagnostic evaluation, morphology, therapeutic modalities, histological
      evaluation, and clinical course were reviewed. Three patients were treated
      surgically and three received palliative irradiation. All had local recurrence or
      distant metasfases within 15 months after concluding treatment. The seventh
      patient refused treatment.

PMID- 9235031
TI  - [Protocol for the endoscopic sinus surgery: comparative analysis of 200 cases].
AB  - A preliminary analysis was published in 1993 of 100 cases of endoscopic sinus
      surgery (ESS) carried out in our service following a protocol that included
      sinusitis, nasal polyps, and other endoscopic nasal procedures. Another 100 cases
      of ESS were analyzed for the present study and compared with the 1993 group.
      Comparative analysis showed improved results in the second series, with fewer
      minor complications and no major complications. These findings confirm the
      general opinion that endoscopic sinus surgery requires an adequate training
      period before optimal results are obtained.

PMID- 9235032
TI  - [Lower antrostomy in surgery of the maxillary sinus: experimental study].
AB  - Inferior nasoantral windows, with or without radical surgical removal of the
      maxillary sinus mucosa, were evaluated in 15 New Zealand white rabbits. After
      three months, specimens were obtained for examination. Bacteriological cultures
      and light and electron microscopic studies were made. Mucociliary clearance was
      studied. Differences were found in the antrostomy patency rate between radical
      antrostomy and inferior nasoantral windows. After three months, the creation of a
      temporary inferior nasoantral window did not change the maxillary sinus mucosa
      and did not increase the rate of sinus infections in rabbits.

PMID- 9235033
TI  - [Incidence of nasopharyngeal cancer in La Rioja (Spain). Epidemiological
      aspects].
AB  - A retrospective study was made of patients with nasopharyngeal carcinoma
      diagnosed at the Hospital San Millan of La Rioja (Spain), between August 1989 and
      August 1995. Epidemiological and clinical factors, and their relation to findings
      from other regional studies, were examined. Most patients had stage III and IV
      (1986 UICC/AJCC staging system) disease, which indicates that the diagnosis
      tended to be late. Primary care physicians should consider this disease in cases
      of nasal obstruction, nosebleed, or seromucous otitis in adults.

PMID- 9235034
TI  - [Calearo horizontal glottectomy in bilateral glottic cancer].
AB  - Bilateral glottic carcinoma is an unusual tumor that presented a surgical problem
      that was not resolved satisfactorily until Calearo and Teatini published their
      horizontal glottectomy technique in 1978, which consists of block excision of
      both vocal cords with part of the thyroid cartilage, and conservation of the
      arytenoids. This laryngeal horizontal glottic technique is analogous to
      supraglottic horizontal laryngectomy. We report our experience with 12 cases,
      indicating the technical details of the procedure, the satisfactory oncological
      and functional results, and current indications.

PMID- 9235035
TI  - [Surgical voice rehabilitation: permanence of tracheoesophageal fistula after
      total phonatory laryngectomy. Long-term follow-up].
AB  - A study of the 10-year follow-up of 152 patients who underwent total phonatory
      laryngectomy (TPL) for surgical alaryngeal voice rehabilitation by
      trachoesophageal puncture (TEP) and prosthesis insertion is reported. These
      patients belonged to a larger group of 270 patients who underwent TPL in our
      department in 1984-1995. Patients who had undergone surgery at least 24 months
      earlier were selected for the purpose of obtaining more reliable conclusions. TPL
      was a valid option for patients with primary or secondary laryngectomy.
      Tracheoesophageal voice conservation was achieved in 83.1% when technical
      surgical conditions and TEP follow-up improved, and dynamic tracheal and
      hypopharyngeal features were better understood.

PMID- 9235037
TI  - [Thyroid nodules: factors suggestive of malignancy].
AB  - The evaluation and management of thyroid nodules is a common problem in medicine.
      In a review of 250 cases of thyroid disease seen at the 12 de Octubre Hospital
      (Madrid, Spain), 191 cases of solitary nodules and multinodular goiter were
      analyzed. The clinical findings, complementary studies, and postoperative
      histology were analyzed to determine the parameters most closely related to
      malignant thyroid processes. The overall rate of malignancy was 22.5%. Major
      clinical factors associated with malignancy were fixation to deep structures,
      cervical lymph node enlargement, and paralysis of the vocal cords. None of the
      complementary tests was absolutely reliable in excluding malignancy, but fine
      needle aspiration biopsy, in spite of its limitations, was the best diagnostic
      tool. Surgery is indicated if the benignity of a nodule cannot be confirmed.

PMID- 9235036
TI  - [Cancer of the larynx in Ecuador].
AB  - A retrospective review was made of 75 cases of laryngeal cancer evaluated and
      treated at the Social Security Hospital of Quito (Ecuador). No exclusively
      supraglottic lesions were found; 67% of cases, were glottic or glottic
      supraglottic. Thirty-two per cent of cases were T1 and T2 and 23% had palpable
      lymph nodes in neck. Most T1 and T2 tumors were treated with radiotherapy (RT)
      and most T3 and T4 tumors with a combination of surgery and RT. The 5 and 10-year
      overall survival rates were 55% and 47%, respectively. The 5-year survival rates
      were: 81% for T1 and T2 tumors and 36% for T3 and T4 tumors (p = 0.0008), 76% for
      N- and 42% for N+, 53% for well-differentiated and 58% for moderately or poorly
      differentiated tumors, 85% for T1 and T2 lesions treated with RT and 67% for T1
      and T2 lesions treated with partial surgery, and 14% for T3 and T4 lesions
      treated with RT and 49% for T3 and T4 lesions treated surgically (non-significant
      differences).

PMID- 9235038
TI  - [Dilatation of esophageal strictures with balloon catheter. Safety and
      effectiveness of balloon dilatation].
AB  - Radioscopically-guided balloon dilation of esophageal stenosis is an effective
      and easily performed palliative procedure. Our experience with balloon dilation
      of esophageal stenosis in 12 patients was reviewed. Every patient underwent 2-5
      sessions. Dysphagia disappeared completely in 2 patients. Ten patients had
      significant improvement. No case of esophageal perforation occurred during
      balloon dilation.

PMID- 9235039
TI  - [Neurosarcoidosis. Sensorineural hearing loss].
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown origin that often
      affects the lungs, eyes, and lymphatic system. Neurological manifestations are
      rare (5-6%). A case is reported of neurosarcoidosis that presented with anterior
      uveitis, lymph node enlargement, lymphocytic meningitis, cochleovestibular
      disease, and right peripheral facial nerve paralysis. Current diagnostic and
      therapeutic methods in this hard-to-diagnose entity are discussed.

PMID- 9235040
TI  - [Parapharyngeal carcinoma of the larynx: current clinical and pathological
      aspects and reports of a clinical case].
AB  - Schwannomas (neurilemmomas) are benign tumors of the nerve sheath arising from
      the Schwann cells in the neural sheath of cranial and spinal nerves. The most
      frequent sites are the peripheral nerves of the head and neck and the flexor
      surfaces of the upper extremities. Parapharyngeal schwannomas are rare, which
      makes them interesting for ear, nose and throat specialists. A new case of
      schwannoma of the parapharyngeal space is reported. Our experience with the
      clinical management and surgical treatment of cervical schwannomas is discussed
      and the literature is reviewed.

PMID- 9235041
TI  - [Primary laryngeal actinomycosis].
AB  - Primary laryngeal actinomycosis is rare. The case of a woman with diabetes that
      presented with a 2-month history of hoarseness and cough is reported. The
      literature is reviewed and the clinical features and histology of laryngeal
      actinomycosis are discussed.

PMID- 9235042
TI  - [Isolated laryngeal involvement as the first manifestation of Wegener's disease.
      A case report].
AB  - A 74-year-old woman with a 4-month history of hoarseness had a granulomatous
      lesion of the vocal cords by laryngoscopy and a normal physical examination.
      Wegener's granulomatosis was confirmed by biopsy. Early treatment with
      trimethoprim-sulfamethoxazole prevented the evolution toward a more severe
      systemic form of the disease. The patient remains asymptomatic a year and a half
      after treatment.

PMID- 9235043
TI  - [Adenosquamous carcinoma of te larynx. A case report].

PMID- 9235045
TI  - Erratum: Prevalence, severity and medical management of asthma in European
      children.

PMID- 9235044
TI  - [Photochemotherapy in the treatment of oral erosive lichen planus. Letter].
AB  - Photochemotherapy with 8-methoxypsoralenes and PUVA has been found to be
      effective in the treatment of superficial skin inflammations, such as lichen
      planus. However, there is little bibliography on the treatment of oral lichen
      planus with PUVA. A case of oral erosive lichen planus was treated with oral
      psoralenes (0.6 mg/kg body weight) two hours before ultraviolet exposure. Twenty
      sessions were held, three weekly, for a total cumulative dose of 35.9 J/cm2.
      After treatment concluded, clinical symptoms and erosive lesions disappeared.
      PUVA therapy may be useful for severe forms of erosive oral lichen planus that do
      not respond to conventional treatment.

PMID- 9235047
TI  - Proceedings of the 6th International Conference on Malignant Lymphoma. Part 1.
      Lugano, Switzerland, June 5-8, 1996.

PMID- 9235046
TI  - Winner of the MOD Young Investigator award 1996.

PMID- 9235048
TI  - Citation for the presentation of the Down Surgical Prize 1995 to John Llewellyn
      Williams.

PMID- 9235049
TI  - Citation for the presentation of the De Puy Prize 1996 to Mr David Patton.

PMID- 9235050
TI  - [Infectious diseases, bioethics and research].

PMID- 9235051
TI  - [Compliance, efficacy and tolerability of the therapeutic regimen recommended by
      National Consensus on Tuberculosis].
AB  - BACKGROUND: To study the degree of adhesion, efficacy, and tolerance of
      therapeutic guidelines advocated by the National Consensus on tuberculosis.
      METHODS: A prospective study of a cohort of 84 patients receiving a diagnosis of
      tuberculosis in a Basic General Health Area between 1-3-1993 and 28-2-1994
      treated with the regimen recommended by the National Council. The patients were
      evaluated clinically and microbiologically during the treatment and during twelve
      months follow-up. RESULTS: Fifty-two patients (61.9%) were male and 32 (38.1%)
      female, aged 29.9 +/- 19.7 years (r = 1-84 years). Seventy-four (88.1%) were
      index cases and 10 (11.4%) household contacts. Eight patients (9.5%) were also
      infected with HIV, 71 (84.5%) presented pulmonary tuberculosis and 13 (15.5%)
      extrapulmonary forms. Therapeutic compliance was correct in 80 cases (95.2%) and
      incorrect in 4 (4.8%). It was well-tolerated in 73 patients (91.2%), there was
      slight toxicity in five (6.3%) and severe in two (2.5%). Seventy-four patients
      (88.1%) were cured, there was one therapeutic failure (1.2%) and five relapses
      (6%). Overall mortality was 4.8% and attributable mortality 1.2%. CONCLUSION: Our
      results seem to confirm a high degree of adhesion, good tolerance and acceptable
      therapeutic efficacy of the scheme proposed by the National Council.

PMID- 9235052
TI  - [Extent of endemic Chlamydia trachomatis in the metropolitan area of Buenos Aires
      (Argentina)].
AB  - BACKGROUND: In this report we inform laboratory results accumulated over ten
      years (1986-1995). The number of cases, and the geographic distribution, allow us
      to present a very reliable data about the dimension of Chlamydia trachomatis
      urogenital infections in Buenos Aires city and we also compare this profile with
      the prevalence of Neisseria gonorrhoeae in the same area and period of time.
      METHODS: Patients were females and males (aged from 15 to 49 years old) attending
      clinics not specialize in Sexually Transmitted Diseases (STD). Intent to
      isolation of C. trachomatis was done in McCoy cells culture. Patients for
      Neisseria gonorrhoeae investigation were a population assisted at the Clinic for
      STD of an University Hospital (aged from 15 to 75 years old). Study for detection
      of N. gonorrhoeae was developed by direct and conventional culture technics.
      RESULTS: 4128 endocervical samples from women with lower genital tract pathology
      were studied and C. trachomatis infection was detected in 25.6 +/- 4.8%. Over
      1206 male urethral samples 29.5 +/- 4.47% shows positive cultures. Except for
      years 1989 and 1990 in which annual percentage of infected women showed slightly
      higher percentage over the global average, the results shows a very stable annual
      values, as it was also found in male patients. Infection in males shows a
      discrete tendency to be higher compare with values obtained in women. Global
      results of the evolution of prevalence of N. gonorrhoeae infection shows a very
      different pattern. Since 1992 we demonstrate a very significant decrease in the
      number of confirmed cases. CONCLUSIONS: We concluded that patients not attending
      a STD clinic, reveal a high and very stable endemic level of C. trachomatis lower
      tract urogenital infections. N. gonorrhoeae in this population is a very sporadic
      or null finding. Prevalence of Chlamydial infection in STD centers is even higher
      and also shows an stable profile. In people attending STD clinics N. gonorrhoeae
      shows a very different kinetics, with an important decrease in prevalence in the
      last five years.

PMID- 9235053
TI  - [Selection of resistance mutants and bacteriostatic and bactericidal activity of
      meropenem and imipenem against Acinetobacter spp].
AB  - BACKGROUND: To evaluate the inhibitory and bactericidal activity of meropenem and
      imipenem against multiresistant isolates of Acinetobacter spp and to compare the
      frequency of mutation for both antibiotics. METHODS: Minimum inhibitory
      concentrations were determined by the agar dilution method. Bactericidal
      activities were evaluated by killing curves method employing 8 times the MIC. One
      step resistant mutant selection was performed by spreading more than 5 x 10(8)
      ufc/ml on agar Mueller Hinton plates containing 2, 4 and 8 times the MIC of
      meropenem or imipenem. RESULTS: In the group of sensitive strains (MIC < 4 mg/l
      for imipenem and meropenem) we detected lower MIC for imipenem than meropenem
      (61.5% of the strains). Strains with reduced susceptibility to imipenem (MIC = 4
      mg/l) were more sensitive to meropenem with MICs equivalents to the sensitive
      group. Bactericidal activity was detected in 6 hs for imipenem and in 24 hs for
      meropenem. Meropenem was bactericidal in 4 clinical isolates with MICs = 4 mg/l
      for imipenem and imipenem was bactericidal in laboratory mutants resistant to
      meropenem. It was no possible to select mutants resistant to imipenem but for
      meropenem the rate of mutation was 1.4 x 10(-9) to 1.0 x 10(-8). Mutants
      resistant to meropenem were susceptible to imipenem and 57% of them were stable.
      CONCLUSIONS: From the laboratory point of view we consider that imipenem is more
      active than meropenem because it presents lower MICs, better bactericidal
      activity, and no risk to select resistance. However meropenem could be useful in
      some strains resistant to imipenem (MIC = 4 mg/l). Cross-resistance was no
      detected so we consider that both antibiotics should be tested against
      Acinetobacter spp. because they are not equivalents.

PMID- 9235054
TI  - [False tuberculosis outbreak caused by specimen contamination in a micro
      bacteriology laboratory: confirmation by molecular techniques].
AB  - BACKGROUND: The authors describe a false outbreak of tuberculosis by
      contamination in sample processing. METHODS: The longitudinal polymorphisms of
      restriction fragments (RFLPs) of 6 strains of Mycobacterium tuberculosis isolated
      in different patients over a three week period and which were apparently
      implicated in an outbreak of tuberculosis were analyzed. RESULTS: Four of the
      strains studied presented identical restriction pattern and the remaining two
      presented totally different patterns. Following study of the clinical histories
      and the epidemiologic relationships three cases of tuberculosis were confirmed.
      The other three strains isolated corresponded to contamination during the
      sampling process. CONCLUSIONS: In a possible outbreak of six cases of
      tuberculosis, molecular techniques have allowed identification of three true
      cases of tuberculosis and have demonstrated contamination during the sampling
      process in three other cases. The latter could not have been shown with the
      clinical and phenotypical data of the strains.

PMID- 9235055
TI  - [Endocarditis caused by group B streptococci in adults].
AB  - OBJECTIVE: To evaluate clinical characteristics, treatment and outcome of group B
      streptococcal endocarditis in nonpregnant adults. METHODS: We included all cases
      of Streptococcus agalactiae endocarditis diagnosed according to the Duke criteria
      between 1980 and 1994 in a 1000-bed university hospital, where a prospective
      surveillance of all cases of bacteremia is regularly performed. RESULTS: There
      were 9 episodes of S. agalactiae endocarditis, that account for the 10.5% of 85
      bacteremia caused by this organism and 2.6% of 336 infectious endocarditis (in
      non-drug abusers) during the study period. They occurred in 6 males and 3 females
      with an average age of 60 years (44-86 years). Three patients had underlying
      disease and three had been previously diagnosed of having valvulopathy. There
      were no cases of prosthetic valve endocarditis. The valves most frequently
      involved were the aortic and mitral valves. Only one patient had large vessel
      embolization. All isolates were penicillin-susceptible (MIC < 0.12 microgram/ml).
      Most of the patients were treated with penicillin plus an aminoglycoside and 6
      patients also underwent surgery combined with the medical therapy after an
      average of 40 days (13-60 days). The overall mortality was 11%. CONCLUSIONS: S.
      agalactiae is a rare cause of infectious endocarditis. Combination of surgery
      with the antibiotic therapy might decrease mortality rates of this infection.

PMID- 9235056
TI  - [Trichinellosis: study of 2 outbreaks in Navarre].
AB  - BACKGROUND: We present two outbreaks of trichinosis occurred in the last two
      years in Navarre. METHODS: After the detection of the initial case, an
      epidemiological study of all people presumably infected was carried out. We used
      the latex agglutination and ELISA tests to detect specific antibodies. We studied
      the characteristics of the infested meat, as well as the clinical symptoms,
      eosinophil counts and serologic status of the subjects. After three and twelve
      months those items were again monitored. RESULTS: 71 subjects who had ingested
      the infected meat were detected. Of them, 67 (94.3%) were enrolled in the study,
      34 being involved in the first outbreak and 33 in the second. 15 (22.5%) of the
      67 cases had symptoms suggestive of trichinosis, 30 (44.7%) had
      hypereosinophilia, and 25 (38%) had positive serologic test results. 25 subjects
      (38%) were diagnosed as having trichinosis. Two groups were made according to the
      characteristics of the meat consumed: 34 subjects (50.7%) had ingested thoroughly
      cooked meat (group A), whereas 33 (49%) had ingested poorly cooked meat (group
      B). After three months, only 5 patients were symptomatic and 10 had a high
      eosinophil count. After 12 months, all subjects were asymptomatic, had normal
      eosinophil counts and negative serologies. CONCLUSIONS: 1) An epidemiological
      survey and serologic determinations for trichina should be carried out when
      studying hypereosinophilia. 2) It is important to insist on the necessity of
      veterinary inspection of home-made pork products. 3) The ingestion of poorly
      cooked pork products increases the risk of Trichinella infection.

PMID- 9235057
TI  - [Nocardia infections].

PMID- 9235058
TI  - [21-year-old woman with odynophagia, dysphagia and an intraesophageal vegetating
      lesion].

PMID- 9235060
TI  - [Fever and cavitated pulmonary infiltrates in a patient with AIDS].

PMID- 9235059
TI  - [Necrotic chin lesion in a patient with a meningeal syndrome].

PMID- 9235061
TI  - [Water-borne disease outbreaks and investigation of epidemics].

PMID- 9235062
TI  - [Recurrent pericarditis caused by Q fever].

PMID- 9235063
TI  - [Meningitis caused by non-serotypable Haemophilus influenzae, biotype V].

PMID- 9235064
TI  - [Myo-pericarditis caused by Toxoplasma gondii].

PMID- 9235065
TI  - [Meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae in a
      non-immunocompromised adult].

PMID- 9235066
TI  - [Cellulitis caused by Streptococcus pneumoniae associated with spondylodiscitis
      after suppurative otitis media].

PMID- 9235067
TI  - [Bacteremia caused by Corynebacterium urealyticum in 2 patients co-infected with
      HIV and HBV].

PMID- 9235068
TI  - [Health personnel as a source of infection in a hospital outbreak of methicillin
      resistant Staphylococcus aureus].

PMID- 9235069
TI  - [Alloiococcus otitidis: a more common microorganism than we thought?].

PMID- 9235070
TI  - [Zalcitabine].

PMID- 9235072
TI  - [Steps toward the primary prevention of type II diabetes mellitus. Various
      epidemiological considerations].
AB  - Non-insulin-dependent diabetes mellitus (NIDDM), or type II diabetes is rapidly
      becoming one of the most common chronic disease in the United States and
      worldwide, with more than 7% of the adult population affected. NIDDM is even more
      common in the elderly and in minority population including Hispanic Americans,
      African Americans, Asian and Pacific Island Americans, and Native Americans. In
      these populations, NIDDM may be present in 10% to as much as 50% of the adult
      population. However diagnosed NIDDM is only the tip of the iceberg of an epidemic
      of glucose intolerance. Impaired glucose intolerance (IGT) is even more prevalent
      that NIDDM; and in addition to be a major risk factor for the development of
      NIDDM, IGT is associated with an increased risk of macrovascular disease. Recent
      advances in research into the etiology and natural history of diabetes have
      increased the knowledge to such an extent that primary prevention of NIDDM is
      becoming a reality. This primary prevention can be implemented a) through a
      population strategy, i.e. changing the lifestyle and environmental determinants
      that are known to be risk factors for diabetes, and b) through high-risk
      strategy, i.e. targeting preventive measures only at those specific individuals
      or groups that are at high risk for the future development of NIDDM. The latter
      is the strategy of the Diabetes Prevention Program (DDP), a clinical study
      sponsored by the National Institute of Diabetes and Digestive and Kidney Disease
      in USA. Twenty five centers were selected to participate in this program. The
      purpose of DPP is prevent or delay the development of NIDDM in those persons who
      are at high risk because they have IGT. DPP will also evaluate if the
      interventions selected to prevent the development of NIDDM can decrease the
      frequency of cardiovascular events and the occurrence and magnitude of the
      cardiovascular risk factors that accompany NIDDM and IGT. Four thousand
      volunteers will be recruited from populations known to be at particular high risk
      fo IGT and NIDDM including the following: elderly, overweight individuals,
      persons with family history of NIDDM, women with history of gestational diabetes,
      and minority populations. In order to be eligible, persons who are older than 25
      years will have to demonstrate IGT with plasma glucose levels 100-139 mg/dl
      fasting and 140-199 mg/dL two hours after a 75 g OGTT. Three study intervention
      were selected based on their potential efficacy in ameliorating abnormal glucose
      metabolism in IGT and on their safety and tolerable profile of side-effects. The
      interventions include: intensive lifestyle intervention which focuses on a
      healthy diet to achieve and maintain at least a 7% loss of body weight and an
      increase in caloric expenditure of at least 700 kcal per week. The drug therapy
      interventions include the biguanide metformin and the thiazolidinedione
      troglizatone. Standard life-style recommendations, which include conventional
      instructions regarding diet and exercise, will be provided to all participants,
      including a placebo treated group which will serve as the control group for the
      study. After randomization, participants will have quarterly evaluations and
      have, in addition, a fasting plasma glucose at semi-annual visits and a 75 g OGTT
      at annual visits. All participants will be followed for three years after the
      study-wide closing date for recruitment, resulting in 3 to 6 years of participant
      follow-up. The primary outcome is the development of NIDDM according to WHO
      criteria (fasting plasma glucose level 140 mg/dL or 2-hour plasma glucose 200
      mg/dL after a 75 g OGTT). Secondary outcome will focus en cardiovascular disease
      and its risk factors and change of glycemia, insulin secretion and sensitivity,
      obesity, physical activity and nutrient intake, quality of life, and the
      occurrence of adverse events.

PMID- 9235071
TI  - [Pulmonary alveolar proteinosis: ultrastructural study of 4 cases].
AB  - Pulmonary Alveolar Proteinosis (PAP) is a rare and diffuse lung disease
      characterized by the abnormal deposition of PAS positive, lipoproteinaceous
      material in the alveolar spaces. It has been related, mainly, to alterations in
      the immune state and to secondary infections. We studied four cases of PAP
      diagnosed by light microscopy. In two cases we were able to demonstrate
      disseminated Histoplasmosis related to immunodeficiency states (AIDS and
      malnutrition), one case with Pneumocystis carinii infection and AIDS, and one
      case with no related pathology. Granular and electron dense material, concentric
      myelin figures, and variable-sized osmiophilic bodies were observed by electron
      microscopy. We found yeast-like structures, trophozoites and cysts in the
      alveolar spaces, in the Histoplasmosis and Pneumocystic carinii infection cases,
      respectively. In one of our cases, the circulating neutrophils showed crystalloid
      inclusions in the nucleus. PAP should be considered in the differential diagnoses
      of patients with pulmonary infiltrates.

PMID- 9235074
TI  - VIIth Workshop Flow Cytometry of Arbeitsgemeinschaft Dermatologische Forschung in
      cooperation with Deutsch Gesellschaft fur Zytometrie. September 12-13, 1996.
      Abstracts.

PMID- 9235075
TI  - New Perspectives of Surfactant Research. Proceedings of the 12th International
      Workshop on Surfactant Replacement. Stockholm, Sweden, May 29-June 1, 1997.

PMID- 9235073
TI  - [Weaver syndrome. 1st case reported in Venezuela].
AB  - A 2 years and 9 months old female patient, with the diagnosis of Weaver syndrome
      is reported. The proband presents persistent pre and post-natal overgrowth,
      asynchronic advanced bone age, particular facies, (macrocephaly, ocular
      hypertelorism, micrognathia, large ears), bilateral widening of the distal
      femoral metaphysis, bilateral tibia vara, prominent fetal fingerpads,
      clinodactyly, development delay, low pitched and hoarse cry, nonspecific cortical
      atrophy, dilation of the ventricles and vermix hypoplasia. The differential
      diagnosis with other overgrowth syndromes is discussed. The possibility of
      uniparental disomy and genetic imprinting as the basic genetic defect in the
      Weaver syndrome is suggested. The patient reported here appears to be the first
      case in the Venezuelan literature.

PMID- 9235076
TI  - [Antibiotic prophylaxis in biliary surgery].

PMID- 9235078
TI  - [Radiographic findings in Pneumocystis carinii pneumonia and its complications in
      HIV patients].
AB  - We have performed a retrospective study of 61 cases of Pneumocystis carinii
      pneumonia (PCP) among the Human Immunodeficiency Virus (HIV) seropositive
      population at the 11th Health Area of the Comunidad de Madrid with
      microbiological diagnosis until January 1994. We made an Epidemiologic analysis
      of this PCP group and compared it with the Epidemiologic data of the general HIV
      population in Madrid. Besides, we studied the radiologic manifestations and their
      possible associations with several factors (sex, HIV risk factor, time of HIV
      risk practice, time of HIV infection, associated infections, number of CD4
      lymphocytes, radiologic secuelae, time of healing, mortality, number of PCP
      episodes, time interval from primoinfection to death). The goal of our study is
      to show the Statistical associations between these variables.

PMID- 9235077
TI  - [Scheduled biliary surgery and antibiotic prophylaxis. Is its use always
      justified?].
AB  - AIM: Evaluate the need to give prophylactic antibiotic therapy in patients that
      undergo elective surgery for cholelithiasis. METHODS: Prospective study in 35
      patients the underwent surgery for cholelithiasis, without infectious risk
      factors. All of them, the hemocultives, endotoxin and Tumor Necrosis Factor has
      been evaluated along the surgical process. RESULTS: The hemocultives were in all
      the patients negatives. The levels of Tumor Necrosis Factor decreased along the
      surgical process, without modifications of endotoxin levels. There were no
      significant differences in either of the points of the analysis. CONCLUSIONS:
      Biliary surgery in patients that undergo elective surgery for cholelithiasis,
      without infectious risk factors, is a clean surgery, and so, in this patients is
      not indicated systematically an antibiotic prophylaxis.

PMID- 9235079
TI  - [Ultrasound diagnosis of salivary gland tumors].
AB  - The ultrasonic diagnosis of salivary gland tumors can give a more accurate
      information than clinical data alone. For example, it will help differentiate
      intraglandular from extraglandular tumors and benign from malignant processes. We
      conducted a prospective study in 39 patients with parotidal or submaxillary
      tumors. Patients were evaluated with a physical exam and a with ultrasound.
      Results indicate that only 53.86% of the physical examinations were correct in
      their diagnosis compared to 87.18% of the those done by ultrasound. Specificity
      and sensibility for malignancy was 96.43% and 81.81% respectively. These results
      were similar to those reported by other authors. We conclude that the use of
      ultrasound techniques in the study of salivary gland pathology is well justified,
      due to its capacity to provide high resolution, improving clinical diagnosis.

PMID- 9235080
TI  - [The short-stay medical unit of La Coruna: our experience].
AB  - During the last years public Hospitals have experienced a progressive saturation.
      This has motivated the development of short stay medical units (SSMU) as an
      alternative to the traditional hospitalization. In our Hospital a SSMU begun to
      admit patients in April of 1994. During the rest of that year, 1814 were admitted
      to the unit with a mean hospital stay of 3.22 +/- 2.0 days. 68% of the patients
      were discharged and 32% were transferred to other units in the Hospital according
      to their diagnoses. 30% of the patients were seen in an external clinic, by the
      same medical staff, shortly after the discharge. Since the unit is functioning,
      the number of ectopic patients of the Department of Medicine decreased to a third
      and the mean hospital stay of all the medical patients decreased by 3.4 days. We
      consider that it is possible to achieve a short medical stay with the support of
      a swift external clinic. The SSMU also improved the allocation of the patients
      throughout the medical units, and contributed to mitigate the number of the
      ectopic patients.

PMID- 9235081
TI  - [Acute liver failure as presentation form of small cell carcinoma of the lung].
AB  - Metastatic infiltration of the liver is an uncommon cause of acute hepatic
      failure. We describe the case of a 55-yr-old man who presented with signs and
      symptoms of liver disease. Diagnostic testing revealed a small cell carcinoma of
      the lung with massive hepatic metastases.

PMID- 9235082
TI  - [Gynecomastia and Leydig cell tumor].
AB  - INTRODUCTION: Leydig cell tumors may generate estrogen production and
      gynecomastia. CASE PRESENTED: A 32-year man asked for medical advice due to
      gynecomastia. He had raised estrogen levels and diminished testosterone/estradiol
      index. A testicular echogram showed a nodular image in the right testis.
      Orchidectomy was performed and the diagnosis of a Leydig cell tumor was
      confirmed. The gynecomastia diminished, and estradiol remained lightly elevated,
      with little response to HCG. DISCUSSION: The more frequent hormonal
      manifestations of these tumors are high plasmatic and urinary estrogen levels,
      low serum testosterone, low testosterone/estradiol index, and FSH or LH low
      levels as well. The low response to HCG, the absence of metastasis and the good
      clinical evolution suggested the tumor was benign. Testicular echography is
      useful in the diagnosis of these tumors.

PMID- 9235083
TI  - [Seip-Lawrence syndrome associated with polyostotic fibrous dysplasia. Report of
      a case].
AB  - We report the case of a 28-year-old woman attending for hirsutism and diabetes
      mellitus. Diabetes was a casual finding 2 years before consulting and was treated
      with diet and antidiabetic drugs. Acromegalic appearance, facial acne, penty,
      curled and rude hair, hypertrichosis, ade I diffuse goitre, prominent abdomen
      with umbilical hernia, severe hepatomegaly, prominent muscles and veins with
      normal genitalia appeared in the physical examination. No other abnormalities
      were found. Hypophysis, thyroid, suprarenal and ovaric hormonal functional
      studies were normal. An insulin-resistant diabetes mellitus was found in the
      metabolic study. Ultrasound and TAC showed severe diffuse hepatomegaly and
      visceral fat lack. Bone radiographies showed diffuse lesions compatible with
      polyostotic dysplasia. Subcutaneous, hepatic and bone biopsy revealed lack of fat
      tissue, hepatic steatosis and osteal fibrosis. Patient s diagnosis was
      Berardinelli-Seip syndrome, Seip-Lawrence or lipoatrophic diabetes associated
      with polyostotic fibrotic dysplasia. Case is studies and bibliographic references
      are reviewed.

PMID- 9235084
TI  - [Neurosarcoidosis mimicking cerebral tumor].
AB  - We report a case of neurosarcoidosis, which simulated a cerebral tumor located at
      the floor of the III ventricle, associated to an aseptic meningitis and diabetes
      insipidus. It was the first and only manifestation of the illness. The response
      to steroid therapy was very favourable, with complete clinical recuperation and
      radiological resolution.

PMID- 9235085
TI  - [Long-course pneumonia as manifestation of transphrenic migration of a calcified
      hydatid cyst].
AB  - The hydatidosis disease, which is caused by the larva of the granulosus
      equinococcus, is still a common zoonosis in countries like Spain. The observation
      of a calcified hydatid cyst of the liver in an asymptomatic patient suggest a
      very long clinical latency period of the disease. Acute complications have been
      reported. We present the case of a patient with clinical symptoms of nonresolving
      pneumonia and an old calcified hydatid cyst of the liver. The first approach to
      the diagnosis of community-acquired pneumonia was inconclusive. The high clinical
      suspect of equinococcus infection added to the bronchoscopy findings, computed
      tomographic (CT) study and serological test, permitted the correct preoperative
      diagnosis. The surgical removal confirmed the diagnosis of transphrenic migration
      of a hydatid cyst ruptured to the bronchial tree.

PMID- 9235086
TI  - [Multidrug resistance (MDR) in oncology].
AB  - Multidrug resistance or mdr is a frequent phenomenon for which tumor cells can
      develop, in only one step, cross-resistance to a different anticancer drugs such
      as antibiotics, vinca alkaloids and podophylotoxins. This is due to an extrusion
      of drugs out of the cells, since it is interrelated with the decrease of the
      intracellular concentration of the drug, compared to sensitive cells. This
      phenomeno of multidrug resistance (mdr) is considered one of the principal causes
      of failure in quimiotherapic treatment of cancer, and is associated in many cases
      to an hyperexpression of mdr-I gene, that codifies for a high molecular weight
      glycoprotein (p-170) (170-180 Kdaltons), also called p-glycoprotein (pgp).
      Locadet it in the cellular membrane extracts, like a pump, the quimiotherapic
      drugs with consumption of ATP. In humans, there are two principal genes that
      codify for pgp: mdr-I and mdr2/3; being the most important the mdr-I gene. The
      structure of p-glycoprotein consists in two symmetrical halves anchored in the
      cellular membrane that includes three extracellular dominances each one, and on
      intracellular portion with the ATP binding site. Also, has got an for
      extracellular carbohydrates chain. It is specially important to find drugs that
      reverse the multidrug resistance. Chemicals such as verapamil, nifedine,
      quinidine and calmodulin inhibitors are joined to pgp inhibiting it. A
      Cyclosporine and its non-immunosuppressors derivateds such as SDZ 280-125 and SDZ
      PSC 833 reverse mdr. At present it is being advancing in clinical trials, but the
      results are not satisfactory. Most useful chemicals are verapamil, better R
      verapamil and A-cyclosporine or its non-immunosuppressors derivates. Futures
      possibilities are grateful. From diagnostic point of view the mains are: 1.
      Detection of mdr-I gene. 2. Recognition of the presence of mRNA for pgp. 3.
      Detection of pgp by flow cytometry or western blot. 4. Immunohistochemistry with
      monoclonal antibodies to pgp. 5. Rhodamine 123 to study mdr phenotype. 6.
      Multidrug resistance modulators in vitro. 7. pgp in vivo as a tumor marker. From
      therapeutic point of view: 1. To assay mdr modulators with higher power and
      better tolerated. 2. Reversing of mdr with in vivo MoAbs and/or immunotoxins. 3.
      Gene therapy. 4. New chemicals that joined to tubulin do not be extrused by pgp.
      5. Drugs joined to liposomes. 6. Interpheron to increase the efficacy of MoAbs in
      mdr reversion. 7. Photodynamic therapy. Other possibilities can be the use of
      MoAbs in diagnostic (immunodetection) by PET and SPECT: and the MoAbs joined to
      drugs and radioisotopes.

PMID- 9235087
TI  - [Hematuria and pleural effusion: are they manifestations of the same entity?].

PMID- 9235088
TI  - [Neuroleptic malignant syndrome: report of a case].

PMID- 9235089
TI  - [Systemic candidiasis in heroin addicts: therapeutic considerations].

PMID- 9235090
TI  - [Brachydactyly: diagnostic sign of Turner's syndrome].

PMID- 9235091
TI  - [A case of protein S deficiency associated with ovarian cancer].

PMID- 9235092
TI  - [Peripheral mononeuropathy as first manifestation of hepatocellular carcinoma].

PMID- 9235093
TI  - [Massive rhabdomyolysis after the first exercise session for muscle development].

PMID- 9235094
TI  - [Slow-release verapamil poisoning].

PMID- 9235095
TI  - [Calcium channel blockers and cardiovascular morbidity mortality].

PMID- 9235097
TI  - [Epidemiologic study of cardiovascular risk factors in Alcala de Henares,
      Madrid].
AB  - We studied the prevalence of cardiovascular risk factors (included arterial
      hypertension, tobacco, diabetes, dyslipemias) in Alcala de Henares population
      during the period 1992-1993, following the WHO criterias and protocols. The
      results upon 12,000 analyzed individuals showed dates similar to other spanish
      studies in relationship with arterial hypertension and diabetes (factors with
      known genetic determinants) and, in lesser degree, with tabaquism and
      hypercholesterolemia.

PMID- 9235096
TI  - [The prevalence of cardiovascular risk factors in a rural population from the
      north of Catalonia (Spain): La Cerdana].
AB  - BACKGROUND: Coronary atherosclerosis is the first cause of death in the developed
      countries. This is a cross-sectional study of prevalence about cardiovascular
      risk factors in a rural population in La Cerdana (Catalonia). METHODS: With the
      aim of studying the cardiovascular risk factors among the Cerdanya population
      older than 18 years a representative sample of 425 individuals was studied with
      participation of 72% being obtained. RESULTS: The prevalences obtained were the
      following: male smoking habit 46%; female smoking habit 15%; obesity (Quetelet
      index > 30) male 13%, females 17%; arterial hypertension (systolic > 140 mmHg
      and/or diastolic > 90 mmHg) in males 9.8%, females 23%; hypercholesterolemia
      (cholesterol > 250 mg/dl) in males 16.4%, in females 18.7%; cholesterol-HDL lower
      than 35 mg/dl in males 12.1%, in females 4.9%; hypertriglyceridemia
      (triglycerides > 200 mg/dl) in males 7.8%, in females 7.1%. CONCLUSIONS: The
      smoking frequency and the prevalence of hypercholesterolemia in La Cerdana are
      lower than in the rest of Catalonia, but the obesity prevalence is higher. It is
      important to know the prevalence of cardiovascular risk factors in aim to
      evaluate the intervention program.

PMID- 9235098
TI  - [Malignant neuroleptic syndrome].
AB  - Neuroleptic Malignant Syndrome (NMS) is a rare disease characterized by
      hyperthermia, altered level of consciousness, autonomic dysfunction and muscular
      rigidity in relation to treatment with different drugs. We describe ten patients
      with Neuroleptic Malignant Syndrome in our Hospital. The mean age was 48 +/- 18
      and females were majority (70%). Haloperidol, alone or with another farms, was
      relation with NMS in the 90% of the cases. Mortality became the 20% and it was
      relation with respiratory failure and delayed on admission in Intensive Care Unit
      (UCI). We remarked the importance to have a high suspicious index for attending
      of this disease by a precocious and intensive treatment.

PMID- 9235099
TI  - [Chlamydia psittaci and Chlamydia pneumoniae infection in Caceres].
AB  - OBJECTIVE: The study of the clinical and epidemiological characteristics of
      infectious process caused by Chlamydia pneumoniae and Chlamydia psittaci in our
      medium, Caceres. METHOD: We are reviewed retrospectively clinical aspects of the
      patients with infections due to Chlamydia in the las five years. We accepted
      patients with compatible symptoms and serologic demonstration of recent infection
      with conventional complement fixation and/or microimmunofluorescence assay, the
      last used to distinguish Chlamydia pneumoniae. RESULTS: We are studied sixteen
      patients (9 males and 7 females), sixth median age 46.6 (26-70). Fifteen patients
      was diagnosed in winter. We found five cases of Chlamydia pneumoniae and three of
      Chlamydia psittaci. In the other eight cases we didn't distinguish between
      Chlamydia pneumoniae and Chlamydia psittaci. All patients had fever, accompanied
      by lung symptoms and pulmonary infiltrates in the 75% of them. The most frequent
      clinical information was the discord between the pulse and temperature (81%).
      Splenomegaly was observed in three patients (19%) being the diagnosis of them
      psitacosis. Nine patients had respiratory insufficiency and eight (50%)
      disturbance in hepatic enzymes. The clinical presentation in one patients was as
      unknown origin fever. CONCLUSIONS: The infection produced by Chlamydia in the
      hospitalary medium isn't much diagnosed in our unit. The months of winter favour
      the infection. We think that splenomegaly is the only different characteristic in
      these infections, suggesting psitacosis.

PMID- 9235100
TI  - [Central motor conduction evaluation in glycogenosis type III].
AB  - We report a 20-year-old man affected by glycogenosis type III with distal muscle
      weakness, more severe in distal leg muscles. The electromyogram showed myopathic
      features. Nerve conduction studies and central motor conduction after magnetic
      stimulation of the brain were normal. Our results suggest that there is no
      involvement of central motor pathways in this disease.

PMID- 9235101
TI  - [Polyarteritis nodosa associated with hepatitis C virus].
AB  - BACKGROUND: To study the seroprevalence of hepatitis C virus in a cohort of six
      patients with a diagnosis of polyarteritis nodosa (PAN). METHODS: There have been
      included six patients with a diagnosis of PAN, carrying out a serodiagnosis of
      hepatitis B virus (VHB) and C (VHC) this last one by means of the following
      methods: ELISA, RIBA-II and PCR. RESULTS: These cases (50%) showed exclusive
      positivity to VHC by means of the three ways of diagnosis, two cases showed
      positivity to VHB (33.3%), one case (16.6%) showed positivity to both virus (VHB
      and (VHC) and one case didn't show positivity virus. CONCLUSIONS: It is probable
      a ethipatogenic relation between hepatitis C virus and polyarteritis nodosa, our
      sample doesn't show any difference from that written in the literature. The
      positive rheumatoid factors can give false positive for VHC by means of the
      technique ELISA because of this it is necessary to confirm the positive by means
      of the techniques RIBA-II and PCR.

PMID- 9235102
TI  - [Association of lung adenocarcinoma and human immunodeficiency virus infection].
AB  - In the past decade, few studies have reported the occurrence of lung cancer in
      HIV-infected patients. The true frequency of this association is known. The major
      features of these patients include: male gender, young age, a history of
      intravenous drug abuse, preponderance of adenocarcinoma cell type and advanced
      clinical stage at diagnosis. We describe a case of a lung cancer in a man with
      evidence of advanced HIV-infection and a history of intravenous drug abuse.
      Subsequently, we review the data reported in the literature about this
      association. Our patient provides further evidence that lung cancer should be
      included in the differential diagnosis of intrathoracic diseases in HIV-infected
      patients.

PMID- 9235103
TI  - [Tuberculosis and HIV infection: epidemiology (the first of three parts)].

PMID- 9235104
TI  - [Atheroembolic disease (cholesterol crystal embolism)].
AB  - The atheroembolic disease, often non recognized and fatal in the elderly, is a
      complication of atherosclerosis characterized by obstruction of multiple small
      arteries by cholesterol crystals. It may occur spontaneously or after aortic wall
      trauma, latter usually following angiography or cardiovascular surgery, and the
      use of anticoagulants. Renal failure, livedo reticularis and acrocyanosis of the
      lower extremities have been frequently described. In some cases the clinical
      picture may resembling a vasculitis. The diagnosis can be confirmed by skin,
      muscle or kidney biopsy. In practice, the treatment is symptomatic. The most
      effective measure is prevention.

PMID- 9235105
TI  - [Acute pulmonary edema induced by psychologic stress].

PMID- 9235106
TI  - [Multiple bone metastasis and bone marrow invasion as an initial manifestation of
      a medullary thyroid carcinoma].

PMID- 9235107
TI  - [Cryptococcal meningitis in an intravenous drug abuse HIV negative person].

PMID- 9235108
TI  - [Fever of unknown origin and psoas abscess].

PMID- 9235109
TI  - [Diagnosis of active tuberculosis by prostatic biopsy in a patient with Addison
      disease].

PMID- 9235110
TI  - [Lethal catatonia: a case report].

PMID- 9235111
TI  - [Infectious endocarditis by Neisseria subflava in two HIV drug users].

PMID- 9235112
TI  - [Isolated central facial palsy from internal capsule lacunar infarction].

PMID- 9235113
TI  - [Intraoperative EEG monitoring using a neural network].
AB  - OBJECTIVE: To introduce a new EEG parameter for monitoring a patient's cerebral
      status during anaesthesia. METHOD: EEG epochs (channel C3 P3, duration 30 see per
      epoch) yield patterns used as the training input of a self-organising neural
      network (neural gas algorithm). Each pattern contains spectral components. An
      additional "suppression parameter" reflects the proportion of flat curves during
      an EEG epoch and reduces the shortcomings of spectral analysis. The enhanced
      pattern vector enables the recognition of burst-suppression periods representing
      depressed cerebral activity during anaesthesia. Following training with 25549 EEG
      epochs ?recorded in 196 consenting patients in the period beginning 5 minutes
      before induction of anaesthesia to extubation? the network knows 125 basic
      patterns (neural clusters). The neural clusters are responsible for different
      stages of anaesthesia: some neurons are activated by EEG epochs of awake
      patients, others are stimulated by deep stages. The homogeneity of the EEG epochs
      of cluster is checked. The portion of the EEG epochs not recognised by the
      network (7.5%) contains heterogeneous and sporadic patterns (mainly outlines
      caused by artefacts). RESULTS: In comparison with commonly used variables of
      anaesthesiological EEG monitoring (spectral edge or median frequency) neural
      discriminant analysis achieves better discrimination between awake and deeply
      anaesthetised stages (reclassification of 96% vs. 70%). On the basis of 56
      complete sequences of patterns (from the beginning of the infusion of
      anaesthetics to the occurrence of burst suppression) a trend value of between 0.0
      and 100.0 is assigned to each neural cluster. In contrast to existing methods,
      induction of anaesthesia causes a strictly linear increase in the
      electroencephalographic trend. CONCLUSIONS: Detailed neural cluster and
      discriminant analysis on the basis of the model described leads to an improved
      EEG parameter which better reflects the hypnotic effects of anaesthetic agents
      and arousal reactions caused by pain stimuli. Misclassifications of awake and
      anaesthetised stages are reduced. The neural network learns to recognize the
      complex changes in EEG patterns during induction of anaesthesia with different
      agents.

PMID- 9235114
TI  - [A method for measuring QT and T duration and beat to beat variability].
AB  - The QT interval duration is an important non-invasive electrophysiological
      parameter that reflects ventricular depolarization and repolarization time. A
      knowledge of QT variability also provides specific information on the normal and
      pathological ventricular myocardium, and the influence of the autonomic nervous
      system. A numerical algorithm was developed for measuring QT interval and T-wave
      duration in the surface electrocardiogram. In comparison with numerous other
      approaches, this method calculates these durations without averaging of QRS
      complexes on a beat-to-beat basis. The main aim of this study was to assess the
      efficacy of this method for characterizing cardiac diseases. In 6 patients with
      hypertrophic cardiomyopathy and a control group of 5 healthy, age-matched
      subjects, different interval durations were calculated. In contrast to the mean
      QT interval duration, only the T-wave duration differed significantly between the
      two groups.

PMID- 9235115
TI  - [Transponder ECG].
AB  - Apart from X-rays, the electrocardiogram (ECG) is probably the most frequently
      employed routine investigation. The 24-hour (Holter) ECG is a valuable diagnostic
      tool both for the general practitioner and the cardiologist. For the patient, the
      procedure can be experienced as something of a nuisance during the course of
      his/her normal life. Not least of the reasons for this are the leads connecting
      the electrodes to the device, which impair the movements of the patient's trunk.
      In addition, the patient feels constrained by a desire to avoid the disconnection
      of the electrodes by uncontrolled movements. Despite positive findings obtained
      by other means, this situation often leads to false negative results, making
      repetition of the procedure at some later date.

PMID- 9235117
TI  - [Uninterrupted gas supply for gas insufflation equipment].

PMID- 9235116
TI  - [Laser Doppler data analysis during interstitial laser thermotherapy with
      magnetic resonance control within the scope of an animal experiment study].
AB  - The aim of the present study was to investigate, using laser Doppler (LD)
      flowmetry, the phases immediately prior to and following experimental,
      neurosurgical laser therapy in animals. Two statistical models obtained on the
      basis of discriminant analysis are described. These models should enable the user
      to classify the sets of parameters calculated from the LD signals. With both
      models which contain 3 and 5 parameters, respectively. 100% discrimination of the
      two phases was attained. The usefulness of the models could be validated by
      results obtained with other models.

PMID- 9235118
TI  - Nonparametric tests for comparing umbrella pattern treatment effects with a
      control in a randomized block design.
AB  - This paper treats the problem of comparing umbrella pattern treatment effects
      with a control in a randomized block design. An extension of the Chen-Wolfe test
      (1993, Biometrics 49, 455-465) and its modification are proposed for both cases
      where the peak of the umbrella is known or unknown. Approximate critical values
      are given and the results of a Monte Carlo power study are presented.

PMID- 9235119
TI  - Tree-structured logistic models for over-dispersed binomial data with application
      to modeling developmental effects.
AB  - This article proposes tree-structured logistic regression modeling for over
      dispersed binomial data. Recursive partitioning is performed using a combination
      of statistical tests and residual analysis. The splitting criterion in cross
      validation is based on the deviance function. A nested grid algorithm to estimate
      the bootstrap parameters is developed. The regression tree procedure provides a
      new approach for exploring in detail the relationship between the binomial
      response and explanatory variables. The proposed procedure is used to model the
      relationship between the incidence of malformation and dose and fetal weight
      using data from a developmental experiment conducted at the National Center for
      Toxicological Research. A conditional Gaussian chain model is used to account for
      the effect of fetal weight by dose.

PMID- 9235121
TI  - Proceedings of the 1st International Conference on Home Care: Developments and
      Innovations. Jerusalem, Israel, May 1996.

PMID- 9235120
TI  - Confidence intervals for the generalized ROC criterion.
AB  - Receiver operating characteristic (ROC) curves are frequently used to assess the
      usefulness of diagnostic markers. When several diagnostic markers are available,
      they can be combined by a best linear combination: that is, when the area under
      the ROC curve of this combination is maximized among all possible linear
      combinations. This maximal area is the generalized ROC criterion, which provides
      a measure of how effective the combination of the markers is. This criterion
      needs to be estimated from the data, and is usually evaluated against single
      markers. In the present paper, we provide confidence intervals for the
      generalized ROC criterion under the assumption of homogeneous covariance
      matrices, derive an approximation for the heterogeneous covariance matrices case,
      and evaluate the approximation via a simulation study. Finally, we present an
      illustrative example.

PMID- 9235122
TI  - [Significance of regional public health research].

PMID- 9235123
TI  - [Routine life style and health behavior--approach to a contradictory
      relationship].
AB  - This study is still under way. Its purpose is to make use of the sociological
      structure of everyday living to arrive at a better understanding of everyday
      health behaviour. We introduce with the following report the theoretical
      framework and study design for introducing initial descriptive results in respect
      of selected questions. We proceed along this path by comparing a quantitative
      random sample with the basic overall pattern, after having described the
      pertaining social structure.

PMID- 9235124
TI  - [Nonparticipation as a factor influencing the value of follow-up studies. Results
      of a telephone 5-year follow-up interview of 55-74-year-old participants of the
      Augsburg 1989/90 MONICA Survey].
AB  - In prospective cohort studies losses to follow-up are the major source of bias.
      This article describes the results of the investigation whether there are
      systematic differences in socio-economic and health-related factors between
      participants in a follow up study and those who are lost to follow-up. Subjects
      included were 1,030 men and 957 women aged 55-74 who participated in the second
      MONICA Survey Augsburg, F.R.G., 1989/90 (MONICA = Monitoring of trends and
      determinants of cardiovascular disease). They were reexamined in 1994-95. In
      1994/95 910 men and 912 women of the baseline study were still alive, 1305
      persons (663 men, 642 women) took part in the follow up by telephone. Altogether
      120 men and 45 women had died since 1989/90. 144 persons were not eligible for
      the study (15 moved away, 5 severely ill persons, 124 without telephone). 373
      persons were classified as eligible non-responders. The response rate was 77.8%
      concerning 1678 eligible persons (men 79.1%, women 76.4%). Non-response has led
      to an underrepresentation of the lower social class (workers, less than 10 years
      of education; household income less than 1500 DM) and of persons living alone
      (single, divorced, widowed; single-person households). In females, non-responders
      were overrepresented by "never employed persons" (odds ratio 3.02; 1.89-4.85). We
      found that the odds of being non-responder for single, divorced or widowed men
      was 3.40 (95 %-CI: 2.20-5.23) compared to married men. Men "without chronic
      diseases" at the baseline study compared with ill men had an odds for non
      response of 1.54 (95%-CI: 1.00-2.37); the odds was 1.38 (95%-CI: 1.02-1.85) among
      women who had described their health status as "not so good/bad" in comparison
      with women with good self reported health. The reported distortions by non
      response could be important in analyses of social conditions of morbidity and
      mortality. The underrepresentation of men without chronic diseases and women with
      bad self-assessment of their health is relevant for the estimates of morbidity as
      health outcome. Both aspects have to be taken into account in the interpretation
      of the results.

PMID- 9235126
TI  - [Public health].

PMID- 9235125
TI  - [Mortality and functional limitations in chronic patients: results of a follow-up
      study of elderly patients after myocardial infarct].
AB  - Long-term care is considered to be a major social medical problem in the elderly.
      Empirical data about mortality and functional deficits in every-day life is
      sorely needed for service programme management, planning, and health care policy
      making. To set up an example for chronically diseased persons a follow-up study
      was conducted on patients suffering from coronary heart disease. The figure of
      1710 probands who had survived their first myocardial infarction at an age of 60
      to 74 during the time period from 1985 to 1992 was based on the register of acute
      coronary events with reference to the population of Augsburg, Germany. The
      probands were followed up in 1995. Hence, the observation time ranged from 2 to
      10 years. 832 subjects (261 women, mean age 73.3; 571 men, mean age 71.9) were
      interviewed using a standardised questionnaire (net response rate 79%). 641 (37%)
      had died. The observed survival rates per year, which had been estimated by the
      life table method, were almost constant (93-95%) with the exception of the first
      2 years (90%). Unexpectedly, the survival rates were not sex-related, but
      dependent on the age at the time of event. Nearly 60% out of the patients aged 60
      64 (n = 577) and 40% out of the persons aged 70-74 (n = 567) survived for at
      least 10 years. On being asked to describe their health status, about 75% of the
      age group 60-64 and 65% of the age group 70-74 rated their general health to be
      at least fair, independent of the years already survived after myocardial
      infarction. Women reported worse overall health than men. To assess the
      functional status a short questionnaire recommended as valid by the Organization
      of Economic Cooperation and Development, was applied (OECD-Index). This indicator
      focuses on sensory deficits and mobility-related dysfunctions. Apart from
      impaired hearing, all self-reported deficiencies occurred more often in women
      than in men. This difference could not be observed in the group of probands older
      than 80. According to the OECD-definition 44% of the subjects (57% of the
      females, 38% of the males) were classified as disabled. The disabled probands
      differed from the non-disabled significantly in subjective complaints and major
      geriatric symptoms (e.g. pain, incontinence). The findings of this study support
      the already suggested purpose to employ both health outcome variables-the self
      rated health and the functional status by OECD-as a comparable standard for
      population surveys.

PMID- 9235127
TI  - [Reliability of expert assessment in disability evaluation within the scope of
      disability insurance].
AB  - With the introduction of the law on the statutory nursing care insurance in
      Germany ("Pflegeversicherung") in 1995, new benefits are provided for the most
      severely disabled people. Provision of benefits is contingent on a standardised
      examination performed by the medical service of the German statutory health
      insurance system (MDK). Results of the first study on the inter-rater reliability
      of this standardised examination are presented in this paper. The study
      population consisted of 218 elderly people (age range 60-99) living in 4 nursing
      homes in Munich. They were assessed by 2 senior medical students and 2 nurses
      using the standardised questionnaire of the MDK. Inter-rater reliability was
      assessed by means of kappa coefficients. Reliability was assessed with regard to
      the summary judgement of disability and the rating of single items (with regard
      to limitations in activities of daily living, mental status or the prognosis).
      Inter rater reliability was higher for the overall assessment of disability
      (kappa = 0.71 between medical students, kappa = 0.66 between nurses) than for
      most of the single items of the questionnaire such as "need of assistance with
      dressing" (kappa = 0.57 between medical students, kappa = 0.66 between nurses) or
      "ability to move" (kappa = 0.58 between medical students, kappa = 0.67 between
      nurses). Kappa-coefficients were particularly low for variables concerning
      prognosis of participants and for the mental status item "self-disorientation"
      (kappa = 0.19 between medical students, kappa = 0.23 between nurses). These
      patterns were consistently observed for the 2 rater groups (student-student,
      nurse-nurse). Between the 2 rater groups there was no substantial difference in
      reliability. However, there was a trend for higher agreement within the group of
      nurses. Although the overall reliability of the assessment of disability is
      relatively high in comparison to many other diagnostic procedures (such as x-ray
      readings), efforts should be made towards further improvement of this
      standardised examination.

PMID- 9235128
TI  - [Empirical analysis of work flow in inpatient nursing homes for the elderly].
AB  - The paper starts by offering a short overview of the state of implementation of
      the 2nd stage of the newly introduced German Long-Term-Care-Insurance
      (Pflegeversicherung). It continues to present results of a detailed descriptive
      analysis of employee activities in (long-term-care-)nursing-homes,
      differentiating by severity of the patients' condition. Surprisingly nurses spend
      a large part of their time (40%) on other than nursing activities. The time spent
      with individual patients varies considerably with sex and the main diagnosis;
      thus significantly more time is spent on (basic and treatment-related) nursing
      care for male patients. Age per se does not appear to influence the time required
      for taking care of a patient.

PMID- 9235129
TI  - [Long-term changes in availability of domestic nursing care based on family
      structure changes--a model calculation].
AB  - A central hypothesis in German family sociology is the observation of a
      disruption of family structures. If this disintegration prevails up to highest
      ages it must, among others, lead to an increasing inability to perform nursing
      care within families. The most important person in case of a need for nursing
      care is the spouse. The main topic of this paper is to determine whether
      demographic and familiar developments in Germany will increase or decrease the
      share of men and women at higher ages with a living spouse within the next
      decades. In spite of a slowly increasing share of the never-married and the
      divorced, on the average elderly men and women will be married to a greater and
      widowed to a much lesser proportion within the next decade. The Dutch LIPRO-model
      is used to calculate the exact numerical developments. The surprising result is
      primarily due to the fact that the actual high shares of the widowed are a
      consequence of distortions caused by the two World Wars. During the next few
      decades, these unusual developments will disappear even among the most elderly.

PMID- 9235130
TI  - [Future population growth in the Augsburg area--model calculations using the
      DEPOP model].
AB  - Regional population forecasts are on average even more uncertain than nationwide
      projections, due to the greater importance of migration and the unstable smaller
      absolute numbers. Other than national projections, local or regional calculations
      do normally have an explicit goal. In this paper, a projection of the population
      and age structure in the region of Augsburg is used to demonstrate some specific
      aspects of local population projections used for public health purposes. If
      institutions of childhood ages are to be projected the results are primarily
      determined by the assumptions on migration. If questions of old age are to be
      answered, the main factor of influence is the development in mortality. Depending
      on the specific alm of a local population projection, the principal insecurity
      about the future should be integrated by calculating confidence bands for those
      demographic parameters, that are most important for the specific question.

PMID- 9235131
TI  - [Day care as a component of comprehensive health care structure after
      introduction of nursing care insurance].
AB  - Detailed time protocols based on direct observation as well as socio-demographic
      and morbidity-related data were collected in Day-Care-Facilities for the Aged and
      the Handicapped (Tagespflege), in order to gain information regarding the users
      and the service activities of these institutions. Women aged 80 years and over
      constitute the main users; they use the facilities between 8 am and 4.30 pm in
      most cases. The analysis of employee activities showed that roughly one quarter
      of the time was spent on specific services of such facilities, e.g. group
      activities, individual activating therapy of patients. Should Day-Care-Facilities
      play an (increasingly) important role in the domestic social service provision
      for the aged and the handicapped, the financing of their costs (on the average DM
      88 per day, not counting transportation cost) must be reconsidered.

PMID- 9235132
TI  - [Regional differences of results of disability assessment for domestic health
      care needs in 1995 and possible explanations].
AB  - In 1995 a statutory nursing care insurance was set up in Germany. The MDK
      (Medical Service of Health Care Insurance Institutions) has been asked to
      evaluate the eligibility of the individual patients. Within a few months after
      this body began its work, strong regional differences in incidence became
      visible. A survey of 1995 MDK records from Bavarian counties was selected to
      determine whether and how sociodemographic or socioeconomic variables may explain
      these differences. An age incidence rate of nursing care, standardised according
      to age and sex, was correlated with a variety of explanatory factors. Only two
      variables in the multiple regression model were statistically significant: the
      refusal rate by local MDK officials and the regional supply of outpatient care
      facilities. Further work is needed to improve the process of evaluation and to
      minimise unexplained regional differences.

PMID- 9235133
TI  - [Legionellosis: clinical and epidemiological data].
AB  - Legionellosis is a contagious disease occurring either sporadically or more
      frequently in outbreaks, the infections being caused by members of the family
      Legionellaceae. The disease may show two clinical forms, i.e.: 1) the pneumonic
      form characterized by fever, pulmonary, neurologic and often hepatic and renal
      affections, severe evolution and high mortality rate; and 2) non-pneumonic form
      similar to influenza infection. Occurrence of the disease was mentioned almost
      all over the world its incidence in Europe reaching 1-3%. The infection sources
      are: warm water supply systems of hospitals, hotels etc.; water cooling towers,
      humidifier of air-conditioning systems, disperses for therapeutically applied
      aerosols, water sprinkling equipment, etc. Incubation period of the disease is 2
      10 days. The factors favoring infection have to be looked for with all the
      conditions generating a decrease in activity of immunization system. Disease
      control steps through eliminating infection sources: water hyperchlorination,
      increase of water temperature in water supply systems at 60 degrees C for short
      periods, detachment of non-functional water pipes from the main trunk line.
      Occurrence of legionellosis is monitored by both active and passive means applied
      within the country and on an international level through the Reference Centres
      for Legionellosis.

PMID- 9235134
TI  - [Recommendations for the prevention and control of staphylococcal infections in
      neonatal units--1996].

PMID- 9235135
TI  - [Sickle cell anemia and malaria--interferences].
AB  - Usually in a population the frequency of lethal recessive genes decreases by
      eliminating the homozygous individuals. In sickle cell disease the decrease of
      the frequency of mutant recessive genes does not take place. The fact that a gene
      which in the homozygous state expressed a serious clinical picture reaches a high
      frequency in a population can be explained only by a process of natural selection
      that would offer the heterozygous an advantage. Starting from the discovery that
      the territories where malaria is endemic, the hypothesis that there might be a
      link between these two disease was put forward. The present essay wishes to
      synthesise the epidemiological studies and the mechanisms of resistance of
      heterozygous HbS/HbA to malaria formerly described.

PMID- 9235136
TI  - [An immunogenicity and reactogenicity study of a purified, inactivated trivalent
      influenza vaccine for parenteral administration prepared for the 1996-1997
      season].

PMID- 9235137
TI  - [An estimation of the degree of antibiotic sensitivity of microbial strains
      isolated in pediatric and neonatal wards].

PMID- 9235138
TI  - [Enterobacteriaceae isolated in eastern Romania: the evolution of ampicillin
      sensitivity in the 1970-1995 period].
AB  - The activity of ampicillin against 3383 Enterobacteriaceae (community and
      clinical isolates), collected in Eastern Romania, during 25 years was tested.
      Data were prelucrated by the box-plot method proposed by Simpson and Donnelly.
      The resistance degree for all species tested has progressively increased. In the
      studied region Enterobacteriaceae strains maintain their natural sensitivity only
      exceptionally: e.g., S. typhi and S. java, with limited circulation.
      Enterobacteriaceae which have contact with the resistance genic reservoir of the
      colon microbiota during the justified or nonjustified antibiotic treatment
      development resistance to usual antibiotics in the same ratio as most existent
      commensals present in this habitat.

PMID- 9235139
TI  - [The appearance of an antibiotic-multiresistant strain of Salmonella typhimurium
      in a pediatrics ward and its spread in the country].

PMID- 9235140
TI  - [The pathogenicity factors of opportunistic bacteria in the family Vibrionaceae
      (II)].

PMID- 9235141
TI  - [The antibiotic and chemotherapeutic resistance of Shigella strains isolated in
      the Microbiology Laboratory of I.P.S.M.P. Neamt in 1991-1995].

PMID- 9235142
TI  - [The comparative aspects of the behavior of antimicrobial agents against 1299
      Shigella strains isolated in the years 1977, 1986 and 1995].

PMID- 9235143
TI  - [An antibiotic sensitivity study of Klebsiella sp. strains isolated between the
      years 1994 and 1996].

PMID- 9235144
TI  - [The antibiotic resistance of Staphylococcus aureus strains isolated in units
      with an elevated nosocomial risk and in outpatient facilities in 1995].
AB  - Antibiotic susceptibility testing in 231 strains of S. aureus isolated from
      patients highly exposed to the nosocomial risk and from patients treated in
      ambulatories for staphylococcal infections revealed significant discrepancies in
      respect to the incidence of multiple resistant strains and dispersion of
      resistance phenotypes. MRSA incidence rose to 58-85% in hospital boards, that
      indicated an "alarm state" which requests the supply of the efficient antibiotic.
      The 27.18% of MRSA between the strains isolated in ambulatories points to the
      risk of spreading this strains abroad the community and into the hospital boards
      and requests the monitoring of the chemotherapy in such of health carry units and
      of the antibiotic "automedication".

PMID- 9235145
TI  - [The specific serological profile in hepatitis B virus infection in children].
AB  - Hepatitis B virus infection (HBV) has a very well known specific serologic
      profile. In the last years the molecular biology methods reveal some "particular
      serological profiles" by genomic mutation. One particular profile consists in the
      absence of anti-HBc total antibodies simultaneously with the presence of HBsAg.
      Our tested group consists of 372 children aged 0.1 to 15 years. The presence of
      HBsAg was determined by ELISA "sandwich" and confirmed by neutralisation test.
      For HIV infection we used two ELISA tests (competitive and indirect) and the
      Western Blot test for confirmation. Of the total, there were 13 children HBsAg
      positive and without anti-HBc antibody (3.49% respectively), 7 of the 13 children
      (53.8%) were dystrophic and 4 were HIV positive (30.76%). From 372 cases, 104
      were HBsAg positive (27.9%) and 53 (14.2%) of them had chronic hepatitis.
      CONCLUSIONS: 1. The particular serologic profile requires the testing of all
      serological markers specific for HBV. 2. This particular serologic profile is
      correlated with HIV positive status and dystrophy.

PMID- 9235146
TI  - [Hepatitis B virus reactivation in patients infected with HIV].
AB  - The authors study the reactivation of B hepatitis virus in three HIV infected
      patients, correlating the moment of reactivation of and the CD4 and CD8
      lymphocytes. Prior to the B viral reactivation, the three patients were with Ac
      HBc IgG (+) in serum, assessing that the presence of AC HBc IgG is insufficient
      to prevent the reactivation and to consider a B hepatitis cured. In two patients,
      prior to the B virus reactivation, AgHBs was (-) in the serum. It is considered
      that the predominant hepatocytolysis mechanism is the viral one, in the stage of
      B virus reactivation in patients with AIDS, the cell immunity mechanism being
      depressed.

PMID- 9235147
TI  - [The effect of products of plant and microbial origin on phagocytic function and
      on the release of oxygen free radicals by mouse peritoneal macrophages].
AB  - The effect of in vivo stimulation with an aqueous extract obtained from roots of
      Symphytum officinale and Cantastim on mouse peritoneal macrophages was
      investigated. The results obtained showed that these products initially activated
      the respiratory burst of the cells and later inhibited it, activating the
      synthesis of catalase, SOD etc. These data suggest that macrophages challenged by
      various ingested antigens destroy them initially through oxygen dependent
      mechanisms and later through enzymatic digestion in order to retain unimpaired
      their epitopes.

PMID- 9235148
TI  - [The options in allocating the responsibilities for implementing public health
      measures to control West Nile virus infection in Romania].

PMID- 9235149
TI  - [The epidemiological considerations of the evolution of HIV/AIDS in Iasi County
      in 1990-1995].

PMID- 9235150
TI  - [The impact of an AIDS hotline service on pupils and students].

PMID- 9235151
TI  - [Opinions on the rights of seropositive persons or AIDS patients and the conduct
      adopted towards them].

PMID- 9235152
TI  - [Epidemiological evaluations of the incidence of posttransfusion hepatitis in
      Iasi County in 1985-1995].
AB  - In the interval 1985-1995 the morbidity rate of viral hepatitis of various causes
      showed yearly variations, an average of 181 cases being recorded. The performed
      investigations revealed markers for viral hepatitis B in an yearly average of 154
      cases for the 11 years under study. Posttransfusion hepatitis had an average
      incidence of 43 cases per year, in 59.1% the markers for viral hepatitis B being
      absent. 93.3% of the cases with posttransfusion hepatitis belonged to the age
      groups over 20 years and workers presented a mean yearly incidence of 28.3% of
      all cases. In 1995 the blood donors with viral hepatitis C antibodies represented
      4.05% and 75% of them belonged to the age groups 21-60 years, 50% of them being
      industrial workers and 40% having the A II blood group. Of the 321 admitted
      cases, 26.7% presented AgHBs, 8.4% AcVHC, in 2.3% markers for both viruses were
      evidenced and in 62.8% of the cases the diagnosis was made on epidemiological
      criteria and serologic exclusion (non A, B, C) without excluding the possible
      intervention of other hepatitic viruses.

PMID- 9235153
TI  - [The prevalence of HBsAg in hospitalized children as a marker of hepatitis B
      virus infection].
AB  - The aim of this study was to determine the prevalence of hepatitis B surface
      antigen (HBsAg) in hospitalised children, as specific marker for hepatitis B
      virus (HBV) infection. Our study group consists of 517 children, 68 of them
      diagnosed with chronic hepatitis. For HBsAg determination we used an ELISA test
      (Labsystems); for some children we also tested by ELISA the following markers:
      the antibodies and anti-hepatitis C virus (HCV) antibodies. From 517 children
      24.28% were HBSAg positive and 75% of children with chronic hepatitis were
      positive for the same marker. Almost 100% of chronic active hepatitis (CAH)
      patients was positive for HBSAg. CONCLUSIONS: 1. The prevalence of HBsAg was much
      higher as compared with the healthy population prevalence; it is a clear prove
      that HBV infection has an important role in chronic hepatitis appearance. 2. For
      all HBsAg positive patients, it is necessary to determine other markers like
      HBeAg-anti-HBe antibodies system as well as markers for other viral hepatitis
      (HDV, HCV). 3. The anti-HBV infection vaccine will reduce significantly the
      prevalence of HBV and HDV infections; 4. Biological molecular technique, like PCR
      will be necessary in our country, in the future, even the price is so high, to
      monitoring the IFN treatment for chronic infection as unique solution for these
      patients.

PMID- 9235154
TI  - [Foci of trichinelliasis in the area covered by the Cluj-Napoca Medical Center
      and Health and Management Services].

PMID- 9235155
TI  - Poverty to have priority in NHS.

PMID- 9235156
TI  - Drug induced psychosis with doxazosin.

PMID- 9235157
TI  - Overcoming racism in the NHS. Those who wish to discriminate should change not
      the candidates.

PMID- 9235158
TI  - Vitamins and minerals. Proceedings of a workshop. Milan, Italy, July 1996.

PMID- 9235159
TI  - [Effect of extracellular Na+ on the alpha-1-adrenergic contractile reaction of
      the rat vas deferens].

PMID- 9235160
TI  - [Characteristics of the stimulatory adrenergic reaction of isolated chick embryo
      amnion].

PMID- 9235161
TI  - [Inadequacy of interpreting cytogenetic and biochemical test results on house
      mice in Turkmenistan].

PMID- 9235162
TI  - [Restriction analysis of the Enmynveem mammoth].

PMID- 9235163
TI  - [Superfamily of alpha-galactosidase MEL genes from Saccharomyces cerevisiae].

PMID- 9235164
TI  - [Stimulating effect of ADP on the calcium ion transport system in yeast
      mitochondria].

PMID- 9235165
TI  - [The role of SUP35 and SUP45 genes in controlling Saccharomycetes cell cycle].

PMID- 9235166
TI  - [Determination of segments of yeast artificial chromosomes, hypersensitive to
      nuclease S1, including a domain of human beta-globin genes].

PMID- 9235167
TI  - [Theoretical evaluation of parameters of equally probable safe single-step
      hypobaric decompression].

PMID- 9235168
TI  - Impact of major air pollutants on human health. Proceedings of the EUROTOX-IUTOX
      satellite symposium to EUROTOX 95. Pilsen, Czech Republic, August 31-September 1,
      1995.

PMID- 9235169
TI  - A celebration and a farewell.

PMID- 9235170
TI  - [Nephrogenic metaplasia of the urinary tract].
AB  - Nephrogenic metaplasia or nephrogenic adenoma is a rare, benign disease arising
      in the urothelium, whose glandular structure resembles that of renal tubules.
      More than 350 cases have been reported in the literature, mostly in adults and
      with a male predominance. The mean age of onset is 31 years for women and 44
      years for men (range: 3 weeks-83 years). The tumour can occur at any level of the
      urinary tract, but bladder involvement is predominant (72%) compared to
      ureteropelvic (19%) or urethral (9%) lesions. The pathogenesis remains unknown,
      but the hypothesis usually adopted is metaplastic transformation of urothelial
      cells in response to prior aggression of the urothelium (surgical operations,
      stones, trauma, etc.). This tumour is an incidental finding in 20% (bladder) to
      90% of cases (urethral or ureteropelvic sites). In the other cases, the
      presenting symptoms and endoscopic appearance are nonspecific. Pathological
      examination is able to distinguish nephrogenic adenoma from other tumours
      (transitional cell carcinoma, adenocarcinoma), although these other tumour types
      may also be associated. The tumour must be treated conservatively, as there is no
      risk of malignant degeneration. The elimination of predisposing factors is
      essential in every case, but is not always able to prevent the recurrences
      observed in 37 to 60% of cases. In the particular context of renal transplant
      recipients, in whom this disease has been exceptionally reported, prolonged
      follow-up is necessary due to the absence of any data concerning the long-term
      course in this clinical context, and the possible carcinogenic risk of
      immunosuppressant therapy.

PMID- 9235171
TI  - [Pancreatic islet transplantation: isolation techniques and in vitro
      immunomodulation].
AB  - OBJECTIVES: To develop pancreatic islet isolation and purification techniques in
      order to be able to test two human pancreatic islet immunomodulation techniques
      on an in vitro model of allograft islet rejection. METHODS: Islet isolation was
      performed according to Ricordi's method, which was slightly modified during the
      study. Purification was performed according to the Euroficoll discontinuous
      gradient method on a Cobe 2991 centrifuge. The results of immunomodulation
      techniques (depletion of cells expressing class II HLA molecules, and
      immunomasking of HLA class I molecules) were assessed in vitro by mixed
      lymphocyte-islet cocultures (MLIC). RESULTS: Seventeen pancreatic islets were
      isolated then purified. Technical improvements increased the yield from 2,247 +/-
      1,984 to 4,567 +/- 990 islet-equivalents per gram. The mean purity was 70 +/- 19%
      (40-90%). Immunomodulation by depletion of class II HLA molecules regularly
      inhibited (84%) MLIC in contrast with masking of class I antigens, which induced
      only a moderate (44%) and inconstant (4 experimentations out of 6) inhibition.
      CONCLUSION: The modifications made to the islet isolation method improved its
      yield and now allow the possibility of clinical applications. The results of
      mixed lymphocyte-islet cocultures suggest that the suppression of nonendocrine
      cells expressing class II HLA molecules on their surface reduces the
      immunogenicity of pancreatic islet grafts.

PMID- 9235172
TI  - [Renal and adrenal involvement in von Hippel-Lindau disease: clinical features
      and therapeutic strategies].
AB  - OBJECTIVES: We report our experience of renal and/or adrenal manifestations of
      von Hippel-Lindau disease and propose a practical approach. METHODS: Eight
      patients (mean age: 43 years) presented with predominant renal and adrenal
      lesions in 6 cases and 2 cases, respectively. RESULTS: All patients are alive
      with a mean follow-up of 8.1 years. A local recurrence after partial nephrectomy
      was observed in two cases. Two patients are in renal failure and are treated by
      dialysis and two patients require hormone replacement therapy for adrenal
      insufficiency. CONCLUSIONS: The predegenerative nature of simple renal was not
      observed. Conservative renal surgery is adapted to small renal tumours, with a
      low cytological grade and without any distant lesions in the same kidney. Radical
      nephrectomy is reserved for large lesions (greater than 5 cm) with a high
      cytological grade. The presence of pheochromocytoma must be systematically
      excluded. Preservation of the adrenal gland in the case of homolateral renal
      surgery for cancer is recommended. The reliability of the genetic test allows
      early diagnosis of this disease.

PMID- 9235173
TI  - [Prognostic factors of renal adenocarcinoma: study of a series of 233 patients].
AB  - OBJECTIVE: To identify certain prognostic factors of renal cell carcinoma in a
      retrospective series of 233 patients. PATIENTS AND METHODS: 233 patients (162
      males and 71 females with a mean age of 60 years) were operated for renal cell
      carcinoma between January 1980 and December 1991. sith a mean follow-up of 41.7
      months. Statistical analysis was performed according to the Kaplan-Meier method
      for survival curves, according to the Mantel-Cox model for univariate or
      multivariate analysis and according to Student's t test and Chi-square test for
      comparison of quantitative and qualitative variables. RESULTS: The operative and
      global mortality was 2.2% and 28%, respectively. The following prognostic factors
      were identified: visceral metastases (p = 0.0001), lymph node invasion (p =
      0.001), symptomatic nature of the tumour (p = 0.0004), local pathological stage
      (p = 0.0001) and nuclear grade (p = 0.0001). Multivariate analysis showed that
      the first 3 factors were the most pejorative (relative risk (RR) = 6.7, 4.6, and
      1.7, respectively). Venous invation, multifocal tumours, and cell type were not
      studied in our series. CONCLUSION: This study confirmed that metastases, lymph
      node invasion and symptomatic tumours were the most pejorative prognostic
      factors.

PMID- 9235174
TI  - [Instantaneous pressure/flow ratio for non-permanent flows. Impact on the
      assessment of urethral resistance].
AB  - OBJECTIVE: To verify the validity of the hypothesis of the almost continuous flow
      necessary for evaluation of instantaneous urethral resistance R by the
      pressure/flow relation R = P/Q2. METHOD: An experimental device allowed
      investigation of the pressure/flow relation for discontinuous flow in a flexible
      tube. The tube was submitted to various collapsing pressures and opened under the
      effect of flow. The flow was discontinuous because of the variations of the
      proximal pressure or oscillations in the hydraulic diameter of the tube. RESULTS:
      These experiments showed that the approximation of continuous flow is justified
      within the limits of precision of the measuring methods used in urodynamics.
      CONCLUSION: The formula R = Q2 is therefore theoretically correct and validated
      by the experimentation. There is no hydrodynamic obstacle to the application of
      this formula to the calculation of instantaneous urethral resistance.

PMID- 9235175
TI  - [Augmentation ileocystoplasty in neurologic bladder].
AB  - OBJECTIVE: The authors evaluated the results of augmentation ileocystoplasty in
      patients presenting with neurogenic urinary incontinence. MATERIALS AND METHODS:
      A prospective study was conducted in 36 patients (25 women, 11 men) 30 of whom
      simultaneously underwent a bladder neck continence procedure. The mean follow-up
      was 32.2 months. RESULTS: Daytime continence was obtained in 32 patients (88.8%).
      Thirty patients (83.3%) were continent a night. The upper urinary tract did not
      deteriorate. One patient developed bladder stones and 2 presented a vesical
      perforation. Urodynamic studies showed an increased functional bladder capacity
      and compliance (p < 0.001) and loss of uninhibited bladder contractions.
      CONCLUSION: Augmentation ileocystoplasty is an effective and reliable surgical
      procedure after failure of conservative management. However, long-term
      complications can occur and regular surveillance is necessary.

PMID- 9235176
TI  - [Clinical value of the study of proliferation and cell activation antigens with
      flow cytometry in bladder cancer].
AB  - The proliferative rate of tumor cells is frequently proportional to their degree
      of aggressiveness. The objective of the present study was to determine the
      correlation between the expression of three antigens associated with
      proliferation and the stage and ploidy of bladder cancers. The reactivity of
      antibodies against the nuclear antigen Ki-67 and membrane antigens T43 and the
      epidermal growth factor receptor (EGFR) was studied by flow cytometry on a series
      of 35 clinical samples of superficial and infiltrating bladder cancer and as well
      as on 5 specimens of normal urothelial cells. A preferential expression of the
      T43 antigen was observed on invasive cancer. EGFR was less frequently expressed;
      however, seven of the nine positive samples were from invasive cancers. Ki67 on
      the other hand did not show any selective expression according to tumor stage.
      When comparing Ki-67 and T43 expression on individual tumor samples, a negative
      correlation was found in that no tumor strongly expressed both markers
      simultaneously. These results suggest that markers of proliferation and
      activation do not all measure the same tumor parameters. Together, they may
      provide prognostic information that may be useful in the follow-up of patients
      with bladder cancer.

PMID- 9235177
TI  - [Stress urinary incontinence and genito-sexual conditions. Study of 35 cases].
AB  - OBJECTIVES: To determine frequency and type of sexual disorders in stress urinary
      incontinence. To determine their physiopathologic mechanisms and psychologic
      impact. METHODS: 35 patients with stress urinary incontinence were prospectively
      investigated with special attention for sexuals disorders. Clinical examination,
      visual analogic scores testing psychologic impact, urodynamic investigation and
      electrophysiologic testing (electromyography, sacral latency and terminal
      pudendal nerve latency measurements) were performed. RESULTS: Sexual dysfunction
      was noted in 86% of the cases. Urinary incontinence during sexual intercourse was
      seen in 28%, anorgasmia noted in 60%. No correlation was demonstrated between
      different parameters (age, anorectal disorders, prolapsus, weight, pregnancy,
      visual analogic scales testing disturbance of the quality of life induced by
      urinary incontinence) and the presence of sexual dysfunction. CONCLUSION: This
      fact suggest that perineal stretch neuropathy, with progressive denervation of
      striated pelvic sphincter musculature due to repeated stretch injury of the
      innervation when the pelvic floor is weak, is not probably the most important
      factor to determine sexuals disorders. Psychogenic factors may be always
      considered in diagnosis and treatment.

PMID- 9235178
TI  - [Prognostic value of a positive single ultrasound-guided prostatic biopsy
      regarding tumor volume and intracapsular nature of prostatic adenocarcinoma].
AB  - OBJECTIVE: Study of the value of a single positive prostatic biopsy in the
      staging of prostatic carcinoma and the significance of the tumour volume. METHOD:
      The clinical, laboratory and pathological parameters were studied in 27
      prostatectomized patients with a single positive prostatic biopsy. RESULTS: The
      length of tumour invasion on the biopsy was 2.6 mm (evaluation on 25 biopsies).
      Six patients (23%) had an extracapsular tumour and 21 (78%) had a significant
      tumour volume. Among the 16 patients with a length of tumour invasion < or = 3
      mm, 13 (81%) had a significant tumour volume. 25% of patients with less than 3 mm
      of invasion on the biopsy and a Gleason score < or = 6 and 12% of patients with
      less than 3 mm of invasion and a PSA < or = 10 ng/ml had a non-significant tumour
      volume. CONCLUSION: The presence of a single positive prostatic biopsy is not
      sufficient to determine the pathological stage of a prostatic carcinoma. In this
      retrospective study, the majority of patients with a single positive biopsy had a
      significant tumour volume > 0.5 cc. No preoperative predictive factor of tumour
      volume was demonstrated.

PMID- 9235180
TI  - [Renal endometriosis. Report of a case].
AB  - In the light of a personal case and a review of the literature, the authors
      recall the specific features of renal endometriosis. This rare lesion, with a
      favourable prognosis, is difficult to diagnose and is rarely diagnosed
      preoperatively. Medical treatment by LHRH agonists is discussed and has been used
      exceptionally.

PMID- 9235179
TI  - [Epithelioma of the penis treated with surgery. Study Group on Urogenital Tumors
      of the National Federation of the Centers for Cancer Control].
AB  - OBJECTIVES: To evaluate the efficacy and morbidity of surgical treatment of
      carcinoma of the penis. This series of patients was derived from a retrospective
      multicentre study (1959-1989), initially concerning 506 patients, all treatments
      combined. METHODS: One hundred and sixty-eight patients treated by surgery or
      surgery followed by external radiotherapy between 1959 to 1989 were included. The
      mean follow-up is 14.4 years and the mean participation is 4.7 years. Total or
      partial amputation was performed as first-line treatment in 89 patients (53%) and
      as second-line treatment in 11 patients (7%). Thirty-two patients received
      external radiotherapy as a complement to surgery. Inguinal lymph node dissection
      was performed as first-line treatment in 68 patients (41%) and secondarily in 19
      patients (11%). Postoperative inguinal radiotherapy was performed in 52 patients.
      Monofactorial statistical analysis of prognostic factors is proposed. RESULTS:
      The 5-year local control rate was 84%; it was independent of the stage of the
      tumour; the survival of the patients dying from any cause was 53%, the
      progression-free survival was 69% and the survival of patients dying from cancer
      of the penis was 75%. The vital prognosis is statistically significant related to
      the lymph node status. No significant relationship was observed between lymph
      node status and tumour stage. 61 complications involving the penis were observed
      in 40 patients (24%). Thirty-seven patients developed complications secondary to
      the lymph node dissection (24 cases of oedema of the lower limbs and 13 cases of
      inguinal sclerosis). CONCLUSION: Surgical treatment ensured a local control
      globally comparable to that obtained with brachytherapy, but unlike this
      technique, the local control is independent of the stage. Brachytherapy should
      not always be performed in favour of mutilation for advanced tumours because the
      iatrogenic effects of brachytherapy are increased in these cases. An approach to
      the treatment of lymph nodes is proposed based on the authors' experience and the
      data of the literature.

PMID- 9235181
TI  - [Diagnosis and treatment of cystic tumors of the adrenal gland. Report of 2
      cases].
AB  - Two cases of cystic tumour are reported. The first consisted of a
      pseudohaemorrhagic cyst of the right adrenal gland discovered during aetiological
      assessment of HT refractory to medical treatment. Plasma and urinary assays did
      not reveal any abnormality suggestive of secreting adrenal tumour. Imaging
      (ultrasonography. CT and MRI) was in favour of a necrotic malignant tumour and a
      normal isotope scan (MIBG iodine 131) eliminated phaechromocytoma. Adrenalectomy
      was easily performed via a subcostal laparotomy and the postoperative course was
      uneventful. The second case consisted of a right adrenal cyst detected
      incidentally on ultrasonography. The laboratory assessment demonstrated only a
      slight elevation of urinary metanephrine and imaging (CT and MRI) was not
      suggestive of a malignant lesion. Simple annual CT follow-up was decided in this
      case. The various pathological types of rare cystic lesion of the adrenal gland
      are described with particular emphasis on their diagnostic and therapeutic
      modalities.

PMID- 9235182
TI  - [Malignant fibrous histiocytoma of the retroperitoneum].
AB  - The authors report two cases of retroperitoneal malignant fibrous histiocytoma
      which is a rare tumour (200 cases reported in the literature). The clinical and
      radiological signs are nonspecific and the diagnosis is based on histological
      examination of the specimen. Surgical resection must be as complete as possible
      to prevent local recurrence. The efficacy of adjuvant therapy has not been
      demonstrated due to the low incidence of this tumour.

PMID- 9235183
TI  - [Cystic lymphangioma of the spermatic cord. Report of a new case].
AB  - We report a new case of spermatic cord lymphangioma in a young patient. It is a
      rare tumor of the lymphatic system. Only eleven cases have been reported in
      literature. This lesion tends to recur despite surgical ablation. The
      pathogenesis of this lesion is still controversial.

PMID- 9235184
TI  - [Uretero-acetabular fistula: report of a case].
AB  - We present a case report of uretero-acetabular fistula in a female complicating
      orthopaedic surgery of congenital coxal difformity. An ileal pedicle graft was
      used to replace the terminal ureter. The difficulty of such complication is to
      choose the best the rapeutic strategy between surgical and non surgical
      techniques. We review here the various urological armamentarium to affront such a
      rare and multifactorial complication.

PMID- 9235185
TI  - [Metabolic assessment of urinary lithiasis in routine practice. Common task of
      nephrologists and urologists of the Lithiasis Committee of the French Association
      of Urology].
AB  - Renal lithiasis is a frequent disease which recurs in more than 60% of cases.
      Effective prevention of recurrence can be obtained once the cause has been
      identified. The laboratory investigation, based on clinical history, analysis of
      the stone and blood and urine assays, achieves this objective. As the stone is
      the main indicator of lithogenic disorders, the investigation must start by
      morphoconstitutional analysis of the stone by reliable physical methods. The
      results of this analysis guide the clinician towards the biochemical factors
      responsible for the lithogenic process and, in some cases, directly to certain
      infectious diseases, such as infections due to urease-positive bacteria, or
      metabolic diseases, such as primary hyperoxaluria, tubular acidosis or enzymatic
      deficits of purine metabolism, without forgetting drug causes, responsible for
      the formation of approximately one per cent of stones. Subsequent investigations
      guided by analysis of the stone are therefore much more selective and rational.
      When the stone is not available, the investigation, graduated according to the
      metabolic activity of the lithiasis, can be guided by its radiological
      appearance. Dynamic investigations are rarely necessary and must be reserved a
      second-line procedures for the most severe forms of calcium-dependent stones. In
      the absence of radiological data and when the stone has not been collected, a
      basic routine blood and urine investigation must be performed looking for
      laboratory factors potentially involved in the stone-forming process.

PMID- 9235186
TI  - [Surgical treatment of La Peyronie's disease].
AB  - Lapeyronie disease is responsible for curvature of the penis, making sexual
      intercourse painful or even impossible. Surgical treatment can be proposed when
      the plaque has remained stable for at least 6 months and after failure of medical
      treatment. It is designed to restore erection allowing penetration. Examination
      after an intracavernous test allows assessment of the deformity and the quality
      of erection. These two objective parameters appear to be decisive in the choice
      of the most appropriate technique. Two types of methods are available:
      cavernoplasties (resection-plication of the tunica albuginea, excision-graft) and
      prosthesis implantations (semirigid, inflatable and flexible implants). This
      paper reviews the various surgical techniques and proposes a decisional flow
      chart based on the results of the intracavernous test.

PMID- 9235187
TI  - [Placement technique of a permanent urethral endoprosthesis].
AB  - By taking into account the properties of this stent, which must eventually become
      completely epithelialized, it is important to clearly define its length so that
      its proximal and distal ends lie in healthy mucosa and the stricture must be
      dilated to allow maximum expansion of the stent. On the other hand, due to the
      severity of periurethral fibrosis, which can advance through the stent, this
      solution is contraindicated in the case of posttraumatic stricture or recurrence
      after urethroplasty. Apart from these contraindications, this is a rapid,
      sophisticated and effective procedure for which the current data of the
      literature are convincing.

PMID- 9235188
TI  - [The Fuhrman's grade].

PMID- 9235189
TI  - [Post-treatment PSA, indicator of radical treatment effectiveness of localized
      cancer of the prostate].
AB  - Prostate specific antigen (PSA) has become essential to the follow-up of radical
      treatment for T1-T2 tumours. Various assays are available, but require a
      correlation coefficient to homogenize their results. PSA is probably the most
      reliable marker for the follow-up of radical prostatectomy (RP), as this
      operation should make PSA undetectable after 3 weeks. Highly sensitive tests,
      with a limit of detection of 0.1 ng/ml, allow the earlier laboratory detection of
      tumour escape (20 to 45%). Anastomotic biopsies are positive in 35 to 50% of
      cases. Seminal vesicle invasion and positive resection margins are more
      frequently associated with recurrence. The doubling time and rate of progression
      of PSA after RP can be used to distinguish local recurrence from metastasis.
      Urinary PSA is not useful in the follow-up of RP, as it is secreted by the
      periurethral glands. The use of the PSA after radical radiotherapy is less
      clearly established, as this treatment is not designed to eliminate all prostatic
      tissue or render PSA undetectable. Therapeutic efficacy is situated between 1 and
      1.5 ng/ml according to the tests and is achieved in approximately 40% of cases
      after 4 years. A PSA level greater than 3 ng/ml at 3 months is indicative of a
      poor prognosis. Prospects for the future include the use of highly sensitive
      assays and reverse transcriptase polymerase chain reaction (RT-PCR) to detect
      circulating prostatic cells. The use of PSA has led to a re-evaluation of the
      efficacy of radical treatments and could influence the indications for adjuvant
      treatments.

PMID- 9235190
TI  - [Penile injuries].
AB  - Penile trauma is uncommon, but can be serious due to its urinary and sexual
      complications. After reviewing the literature, the authors examined three types
      of trauma of particular interest because of the specificity of the lesions
      induced and their treatment. The circumstances of onset, the various lesions
      observed, the complementary investigations required, and the therapeutic
      modalities are studied for each type of trauma. Fractures of the corpora
      cavernosa are diagnosed clinically. When in doubt, cavernography is the
      examination of choice. Treatment must be surgical by suture of the defect of the
      albuginea. Strangulations can lead to ulceration of the skin and urethral
      fistula. The causes of strangulation are varied, including the very unusual case
      of strangulation by a hair in a young circumcised boy. Automutilations of the
      penis are rare, but, after psychiatric assessment, microsurgical reimplantation
      can be performed with good functional and aesthetic results.

PMID- 9235192
TI  - Several observations concerning cercarial sheddings of Fasciola gigantica from
      Lymnaea natalensis.
AB  - The shedding of cercariae from Lymnaea natalensis and their transformation into
      metacercariae occurred mainly at night, and 70.7% of the cysts were counted
      between 7 p.m. and 1 a.m. There is no infradian rhythm in the numerical
      distribution of the daily mean values as related to experiment duration or patent
      period duration. One quarter of the snails shed their cercariae in a single wave
      and the others in 2 to 13 waves. Floating cysts represent 35% of the total number
      of metacercariae and their number decreased during the two first waves of
      shedding. Aberrant metacercarial localizations were noted on the inner surface of
      the shell when the snail died.

PMID- 9235191
TI  - [Description of Eimeria mulardi n. sp. from the hybrid duck. Study of the
      endogenous phase of its developmental cycle with demonstration of intranuclear
      development].
AB  - A new species of coccidium. Eimeria mulardi n. sp., has been described from the
      mule duck. The endogenous cycle is studied in experimentally infected ducks. A
      least two generations of meronts were observed, mainly in the lamina propria of
      jejunum and ileum and the gametogony occurred principally in glandular cells of
      the intestinal tract, except in duodenum. All the endogenous stages were
      localized in the nucleus of the cell.

PMID- 9235193
TI  - [Contribution to the study of Microphallidae travassos, 1920 (Trematoda). XLVI.
      Description of Floridatrema heardi n. gen., n. sp., parasite of Oryzomys
      palustris (Mammalia) of the United States].
AB  - The authors describe the adult of the trematode Floridatrema heardi n. gen, n.
      sp., parasite of the intestine of Oryzomys palustris (Mammalia:Rodentia) in
      Florida (USA). The new genus is placed among the Microphallidae, Maritrematidi,
      Maritrematinae, Maritrematini; near the genus Maritrema Nicoll, it is
      characterised by vitellaria in the form of a horseshoe and the anterior extension
      of two symmetrical uterine loops as far as the level of the pharynx, the left
      anterior uterine loop proceeding from the uterus proximally. The species lacks a
      spiny atrio-acetabular plate and concentric rings in the afferent sub-tegumentary
      musculature. The anotomical phenomenon of the anterior extension of the uterus in
      the Microphallidae is discussed.

PMID- 9235194
TI  - [Ultrastructural similarity of spermatozoa of some Cyclophyllidea].
AB  - The mature spermatozoa of Cotugnia polyacantha, Raillietina (R) tunetensis,
      Inermicapsifer madagascariensis and Avitellina centripunctata have an almost
      identical ultrastructural organization. They are tapered at both extremities.
      Their anterior extremity exhibits an apical cone of electron dense material and
      one or two helicoidal crested-like bodies. Their cortical microtubules are
      spiralized and are seen, in longitudinal and cross sections, as continuous,
      dense, submembranous material. Their nucleus is a cord of dense chromatin, coiled
      in a spiral around the 9 + "1" pattern axoneme. The cytoplasm is moderately dense
      to electron lucent and exhibits irregularly spaced walls of proteinaceous
      material and a fine periaxonemal sheath of dense material. In this work we show
      that the Anoplocephalidae are close to the Davaineidae by the characters of the
      spermatozoon and that Inermicapsifer should be put back among the Davaineidae,
      according to the opinion of Joyeux & Baer (1961) and come into conflict with
      other works more particularly Schmidt (1986).

PMID- 9235195
TI  - [Role of Culex quinquefasciatus in the transmission of bancroftian filariasis in
      the Federal Islamic Republic of Comoros (Indian Ocean)].
AB  - In October 1988-January 1989, as a part of a malaria and filariasis control
      programme in Federal Islamic Republic of Comoros an entomological survey was
      carried out in 19 rural and urban localities of Grande Comore. Anjouan and Moheli
      Islands. The potential breeding places were examined and pyrethrum spray catches
      were made to evaluate the indoor resting densities of mosquitos. A total of
      14.578 adult mosquitos potential vectors of filariasis was collected: 94.5% Culex
      quinquefasciatus, 3.5% Anopheles gambiae s. str. 1.9% A. funestus and 0.1% other
      anopheline species. A. funestus, uniformly spread in Moheli, was present only in
      the south-west coast of Anjouan and absent in Grande Comore. A. gambiae and Cx
      quinquefasciatus were present in Grande Comore. A. gambiae and Cx
      quinquefasciatus were present in the three islands with different densities in
      the villages. Only Cx quinquefasciatus specimens la maximum of 150 for each
      locality) were dissected to search filaria larvae being the Anopheles specimens
      used to evaluate the malaria transmission. The global infection rate (9.4%) and
      the infectivity rate (0.9%) observed in Cx quinquefasciatus are higher than
      indices reported in previous surveys. All the larvae in the third development
      instar (L3) were identified as Wuchereria bancrofti. The results suggest that in
      FIR of Comoros W. bancrofti is well adopted to local Cx quinquefasciatus
      population. Because of the presence of high mosquito density this species plays a
      prominent role in the transmission of lymphatic filariasis in that area. The high
      transmission levels calls for the implementation of a specific control program.

PMID- 9235196
TI  - [The colonization of forested areas by Ixodes ricinus (Linne, 1758) in France:
      use of the roe deer, Capreolus capreolus (L. 1758) as a biological marker].
AB  - The roe-deer is a wild animal for which Ixodes ricinus has a particular fondness.
      Its territory is similar to that of the ticks and it is a species which is found
      throughout France yet which rarely leaves its territory. Given these conditions,
      a systematic parasitological examination of the ungulate can provide pertinent
      information concerning the forests inhabited by the tick. Since it is difficult
      to conduct a thorough examination of a large number of roe-deer over a limited
      space of time and on a large territory, the best solution is to examine the hind
      feet (hooves and tarsus) of the animal which are widely covered by the
      preimaginal stages of the tick. This biological material is easily available to
      the extent that the measurements of the animals are often used for game
      management. A preliminary study was conducted in Dordogne (southwestern France).
      Out of the 137 pairs of feet examined more than 50% carried the tick species
      (larvae or nymphs). The critical analysis of the results obtained throughout the
      investigation enables us to be more specific about the conditions of application
      of the advocated method.

PMID- 9235197
TI  - [New localities for Phlebotomus mariae Rioux, Croset, Leger et Bailly-Choumara,
      1974, in Morocco].
AB  - Phlebotomus mariae was first described in the South of Morocco in 1974. More
      specimens were found again recently in the High Atlas, showing that this species
      can be considered as a valid one, placed in the sub-genus Larroussius. The female
      remains to be found.

PMID- 9235199
TI  - [The pharyngeal dentition of the females of Phlebotomus duboscqi Neveu-Lemaire,
      1906 and of Phlebotomus papatasi (Scopoli, 1786) (Diptera: Psychodidae)].
AB  - Phlebotomus duboscqi and P. papatasi are morphologically closely related species.
      Scanning electron microscopy showed constant differences between pharyngeal teeth
      of the females.

PMID- 9235198
TI  - [Demonstration of two twin species A and B of the Aedes detritus (Haliday, 1833)
      complex from the Atlantic coast of France].
AB  - The electrophoretic analysis of five natural populations of Aedes detritus has
      shown that the two sibling species A and B of the complex, described in 1977 in
      an other geographical area by Pasteur et al., cohabit on Atlantic coastline in
      France.

PMID- 9235200
TI  - [Leishmania infantum variant MON-24 isolated from a cutaneous lesion acquired in
      the suburban area of Nice (France)].
AB  - The authors describe a case of cutaneous leishmaniasis in the suburb area of Nice
      (France). The parasite is identificated as Leishmania infantum zymodeme MON-24.
      It is the first report of this dermotropic strain isolated from an autochtonous
      cutaneous lesion in France.

PMID- 9235202
TI  - [Phlebotomus perfiliewi Parrot, 1930 (Diptera, Psychodidae) from the southeast of
      France].
AB  - The authors report the result of an entomological study in the southeastern
      France. It is the first time that Phlebotomus perfiliewi is described in that
      country.

PMID- 9235201
TI  - [Biosystematic study of two populations of teleosts (Sardina pilchardus) and
      their copepod parasites (Peroderma cylindricum) from the Tunisian coast].
AB  - A genetic analysis realized, on Tunisian coasts, within and between two
      populations of a Teleostean (Sardina pilchardus) on one hand, and two populations
      of their parasitic Copepods (Peroderma cylindricum) on the other hand, reveal
      that: (l) the 14 loci analysed are monomorphic in the Teleostean populations;
      (II) 3 loci among 13 investigated are polymorphic in the Copepod populations.
      Statistical tests from deviations of Hardy-Weinberg equilibrium and genotypic
      homogeneity show the existence of strong gene flows within and between Copepod
      populations. Thus, it seems that the Teleostean (Sardina pilchardus) and the
      Copepod (Peroderma cylindricum) constitute at least on Tunisian coasts, two
      homogeneous taxinomic units.

PMID- 9235203
TI  - [Aggressiveness of Simulium of the ornatum complex (Diptera: Simuliidae) in
      Catalonia (Spain). First observation].

PMID- 9235204
TI  - [The necessity of conducting to the end the activities of vector control in the
      onchocerciasis control program in west Africa: recall of the stakes and proposal
      of a minimum budget for the period 1998-2002].
AB  - After a brief presentation of the Onchocerciasis Control Programme in West Africa
      (OCP), the authors realize the health and socioeconomic consequences that could
      follow a cessation of larvicide treatment before 2002 in the south-eastern and
      western extensions of the Programme. Taking into account that OCP activities are
      theoretically supported until 1997, but aware of financial constraints that will
      probably increase from now to 2002, this paper proposes an a minima estimation of
      the residual vector control activities for a "phasing out" spread out for five
      years (1998-2002). These estimations essentially concern the larvicide coverage,
      the insecticides used, the entomological surveillance, the logistical support and
      their financial aspects. As far as 48 U.S. $ million amount for 5 years are
      concerned, the budget allocated for vector control activities should not exceed
      the third of the global amount allocated to OCP for the actual fourth financial
      phase of the Programme (1992-1997).

PMID- 9235205
TI  - Immunohistochemical analysis of the mucosal lesion in mucocutaneous
      leishmaniasis.
AB  - Using antibodies against surface antigens of inflammatory cells and against extra
      cellular matrix components, immunocytochemical studies permit the investigation
      of the in situ cellular immune response and the associated fibrosis, in mucosal
      lesions. 57 paraffin embedded skin biopsies of mucocutaneous leishmaniasis
      originating from Bolivia, and due to Leishmania (Viannia) braziliensis, were
      studied. Memory T cells predominate within a non-organized granulomatous
      reaction, in which were observed proliferating macrophages. At the top of the
      lesion, epithelial cells expressed HLA-DR. Some characteristics of this lesion,
      particularly its chronic destructive pattern, presently lack any clear
      explanation.

PMID- 9235206
TI  - [Biology of the vectors and transmission of Plasmodium falciparum, P. malariae
      and P. ovale in a village in the savanna of west Africa (Dielmo, Senegal)].
AB  - From April 1990 to March 1992 a longitudinal entomological study was carried out
      in Dielmo village, Senegal, an area of Sudan-type savanna. Mosquitoes were
      sampled by night-bite collections and pyretnrum spray collections. Seven
      anopheles species were identified: An. gambiae s.s. An. arabiensis, An. funestus,
      An. pharoensis, An. rufipes, An. squamosus and An. ziemanni. Present throughout
      the year, An. gambiae s.l. and An. funestus represented more than 98% of
      anopheles captured on man. A yearly wave of An. gambiae s.l. was observed in the
      rainy season and An. funestus was generally more abundant in the dry season. The
      sporozoite rate was 1.5% and 1.3%, respectively, for these two species.
      Sporozoite typing by monoclonal antibodies indicated that the proportion of
      infected salivary glands was 92.7% P. falciparum, 18.2% P malariae and 8.2% P.
      ovale. The inoculation rate was calculated to be respectively 111, 21 and 8
      infective bites per human for P. falciparum, P. malariae and P. ovale during the
      first year. Transmission was highest in the second year, with respectively 272,
      54 and 25 infective bites per human.

PMID- 9235207
TI  - [Ecoepidemiology of Lyme borreliosis in the Rhone-Alps region. Distribution,
      ecological context, relationship to the distribution of Ixodes ricinus (Linnaeus,
      1758)].
AB  - The aim of the study was to precise the geographical repartition of Lyme
      borreliosis in the Rhone-Alpes district, to describe the ecological
      characteristics of the areas propitious to the disease, and to verify the
      vectorial competence of I. ricinus. The cases of Lyme disease were located by
      means of a questionnaire sent to 1156 physicians. The vector role of I. ricinus
      was studied by two ways: firstly by searching a correlation between the
      geographical repartition of the tick and that of cases, secondly by proving the
      Borrelia infection of the tick. Lyme disease is widely spread in the study area,
      mainly at the foothill level, its repartition is largely coinciding with that of
      I. ricinus which was found infected by B. burgdorferi (s.l.). However a few
      cases, located near the Mediterranean area, set an unanswered problem.

PMID- 9235208
TI  - [Oslerosis of the dog: diagnostic and therapeutic status].
AB  - Oslerus osleri is a metastrongle whose first-stage larvae are expectorated by the
      bitch, and which are infecting for pups; few cases are described from France. The
      biological features of this parasite, diagnosis and therapy are described in a
      first bibliographic part. 29 of 66 dogs examined were infected with Oslerus
      osleri. We investigated the cause of their chronic coughing, which was not cured
      by routine therapies. Several diagnostic methods were used, of which endoscopy
      was the best. The following drugs were used to treat infection with Oslerus
      osleri: ivermectin, levamisole, oxfendazole and fenbendazole. The last-mentioned
      two drugs are safe for dogs and very effective against this parasite.

PMID- 9235209
TI  - [Influence of the nature of the ingested blood on the gonotrophic parameters of
      Phlebotomus perniciosus under laboratory conditions].
AB  - A laboratory study was conducted about the duration of developmental stages and
      the productivity connected with the type of blood meal ingested by the female of
      Phlebotomus perniciosus. The pre-oviposition and egg incubation periods are not
      affected whatever the blood ingested by the female. The shorter time required to
      achieve larval development (rabbit) and pupal development (hamster) governs the
      generation time, shorter than in the other hosts (dog and man). The productivity
      is greater when blood is ingested from the rabbit and the dog. This is mainly due
      to the smaller number of eggs retained in females with these hosts.

PMID- 9235210
TI  - [Bases of the integral indicator in the determination of the category of work
      intensity].
AB  - Physiologic and clinical examination of mental workers (19 occupational groups)
      helped to justify and calculate integral parameter evaluating the work intensity,
      to determine 6 categories of work intensity. Physiologic and clinical data prove
      that higher integral parameter of work intensity (category of work intensity)
      correlates with higher degree of strain at work and higher share of the diseased
      individuals. The results help to improve classification of hygienic criteria for
      evaluation of work conditions, in particular the work intensity.

PMID- 9235211
TI  - [Achievements and prospects in railway transport hygiene].
AB  - A unique Institute of Railway Hygiene was created 70 years ago in Russia, one of
      the major railway countries in the world. Since then the Institute's staffers
      have carried out huge work on improvement of railway workers' health, prevention
      of their exposure to noise, unfavorable microclimate, vibration and other
      occupational hazards. Significant contribution into the world occupational
      hygiene was made by such Institute's professionals as S.F. Kazansky, P.I.
      Nikitin, A.M. Volkov and others.

PMID- 9235213
TI  - [Adaptational autoregulation of humans during work activities (literature
      review)].

PMID- 9235214
TI  - [Features of the relationship of electromagnetic fields and biological objects
      and their shielding].

PMID- 9235212
TI  - [Analysis of cause of death of workers of non-ferrous metal industry in the Far
      North].
AB  - Mortality parameters among able-bodied individuals engaged into nonferrous
      metallurgy due to cardiovascular, respiratory diseases and malignancies several
      times exceed the analogous parameters among general population residing in the
      same climate (5.4, 4.9 and 3.6 times respectively). High mortality due to
      malignancies among the workers exposed to nonferrous metals does not match the
      data by official statistics declaring the occupational malignancies rate over 400
      times lower than the mortality parameter. Such gap between actual and official
      statistics could result from inadequate occupational medical service for these
      workers.

PMID- 9235215
TI  - [Classification of work hardness and bases of allowable and optimal parameters of
      physical activity according to intensity of dynamic muscular work].
AB  - The authors elaborated Classification of work hardness, justified allowable and
      optimal parameters of physical activity according to capacity of dynamic muscular
      work. The authors also analysed methodic documents on regulation of dynamic
      muscular load, considering ergonomic and physiologic effects of human muscular
      activity.

PMID- 9235216
TI  - [Experimental bases of the use of pharmacologic agents aimed at higher heat
      resistance of humans as means of individual protection].
AB  - A group of volunteers was exposed to action of heating microclimate (ambient
      temperature 30 +/- 1 degrees C, relative humidity 35 +/- 5%) and other critical
      occupation factors (physical loading, personal protective equipment). They
      received simultaneously one of the medicines: placebo, bemethyl (0.5 g), phenibut
      (0.25 g), obsidan (0.08 g), or phenibut (0.25 g) combined with obsidan (0.08 g).
      Combined phenibut (0.25 g) with obsidan (0.08 g) were proved to be the most
      effective method to increase stability of the human body against studying
      critical occupational factors.

PMID- 9235217
TI  - [Fibrogenic and general toxic effects of copper and nickel sulfide ore dust (data
      for a hygienic evaluation)].
AB  - Experiments on acute and chronic inhalation of copper and nickel sulfide ore dust
      proved that the dust of rich ore, if compared with that of copper-bearing and
      impregnated ore, induces more marked toxic effects. Intratracheal administration
      of all the dust types, 50 mg, and inhalation of the high concentrations (102
      mg/cu m in average) induced fibrogenic effects. The dust of rich ore induced more
      marked fibrogenic reaction in lungs, in 3 months after 6-month period of
      inhalations stopped that reaction disappeared. General toxic effects caused by
      the dust either of rich ore or impregnated ore were mild. Justifying the MAC
      requires consideration of possible carcinogenic effect.

PMID- 9235218
TI  - [Biochemical changes and criteria of their significance in exposure to
      polymetallic catalyzer].

PMID- 9235219
TI  - [Hygienic and biomedical aspects of the effects of infrasound].
AB  - The work lists the sources of infrasound and its spectral characteristics.
      Working places are classified by infra-low frequency band noise characteristics;
      the factor is graded by the health risk zones and also by classes of harm and
      danger for the health of the workers depending on the factor parameters.
      Volunteer cochleovestibular apparatus reaction peculiarities are revealed and
      infrasound induced hypothalamic symptom-complex development possibility
      estimation method is presented.

PMID- 9235220
TI  - Virus versus antibody.
AB  - Variation in the proteins produced by animal viruses allows the virus to reinfect
      the same host, but is constrained by the requirement to maintain critical viral
      functions, in particular engagement with cellular receptors. The fundamental
      characteristics of proteins and their interactions with each other suggest that
      this may not be so much of a constraint at all.

PMID- 9235221
TI  - Disasters, the media and social structures: a typology of credibility hierarchy
      persistence based on a newspaper coverage of the Love Canal and six other
      disasters.
AB  - The starting-point of this paper is the assumption that credibility and the right
      to be heard are differentially distributed in any social system and therefore a
      'hierarchy of credibility' exists. To test this, the media coverage of the Love
      Canal, New York, hazardous waste landfill disaster and six other disasters was
      examined to determine if this hierarchy exists in all cases. A hierarchy of
      credibility emphasising the views of established news sources with routine and
      habitual access to the media was demonstrated in the majority of events examined
      However, the Love Canal disaster was one of two where this hierarchy was
      disrupted due to a number of factors. These included the contentious or political
      nature of the event, its duration, the extent of competition of credibility and
      coverage among news sources, the extent of information shortage, the type of news
      medium, the degree of sympathetic and representational salience of victims and
      the extent to which they organized and achieved status as 'newsmakers'. Building
      on disaster research, a model of the operation of the credibility hierarchy in
      coverage of disasters is presented and discussed.

PMID- 9235222
TI  - A research note about military-civilian humanitarianism: more questions than
      answers.
AB  - 'Military-civilian humanitarianism'--or the coming together of military forces
      and civilian aid agencies to deal with the human suffering from complex
      emergencies--has numerous forms, but disenchantment has resulted from the Somalia
      and Bosnia syndromes. There is little political will at present, but evidence
      from the immediate post-Cold War era suggests how multilateral military
      operations could expand or contract in future to the benefit or peril of war
      victims. Partly a literature review but more importantly a framework for
      interpreting recent publications, this essay seeks to move beyond exchanging
      assertions. There is a contextualisation of recent literature; a definition of
      military-civilian humanitarianism; a discussion of possible military
      contributions to humanitarian action; a framework to assess the effectiveness of
      military-civilian humanitarianism; and a preliminary analysis of experience from
      northern Iraq, Somalia, Bosnia, Rwanda and Haiti. Caveat lector: At this point in
      time, there are still 'more questions than answers'.

PMID- 9235223
TI  - [Eulogy of Paul Pialoux (1914-1996)].

PMID- 9235224
TI  - [Recourse to particular arterial embolization in the treatment of some uterine
      leiomyoma].
AB  - In 88 women between the ages of 34 and 51 years with one or several symptomatic
      uterine leiomyomata (menometrorrhagia, mass syndrome) after failure of medical
      treatment, particulate arterial embolization was proposed as an alternative to
      the scheduled surgical operation. Free-flow embolization with Ivalon particles
      (150 to 600 microns) was performed under local anaesthesia after femoral artery
      puncture and catheterization of the hypogastric then uterine arteries (5 F
      catheter) including occlusion Pelvic pain was frequently observed immediately
      after embolization, lasting 12 to 18 hours, and required analgesia. Necrobiosis
      syndromes can be observed in the case of very large leiomyomata. No immediate
      complications directly related to vascular catheterization were observed in this
      series, but complete necrosis of a very large leiomyomatous uterus required
      hysterectomy. Five embolization failures were observed. The following results
      were observed in the 80 interpretable cases with a follow-up of 6 to 60 months:
      the menstrual periods returned to normal in 60 (89%) of the 67 menorrhagic
      patients, after six months a volume reduction of myomata equal to 69% of initial
      volume was observed. CONCLUSION: in of 80 interpretable cases, embolization
      constituted an alternative to surgical treatment, which was avoided in 71 cases,
      9 failures were observed. The results of this preliminary series must be valited
      by further studies.

PMID- 9235225
TI  - [Low extracellular pH has a role in the induction of NO synthase type 2 in
      macrophages].
AB  - Stimulation of macrophages with endotoxin and/or cytokines is responsible for the
      expression of the inducible isoform of nitric oxide synthase (iNOS). Because
      macrophages are exposed to low pH within the microenvironment of inflammatory
      lesions, the potential role of low pH as an additional regulator of iNOS was
      investigated. Substitution of the culture medium of rat peritoneal macrophages at
      pH 7.4 with medium at pH 7.0 upregulated iNOS activity, as reflected by a 2.5
      fold increase in nitrite accumulation. The increase in iNOS activity was
      associated with a similar increase in iNOS mRNA expression. Low environmental pH
      induced iNOS gene expression involved the activation of nuclear factor-kappa B
      (NF-kappa B) transcription factor since [1] exposure of macrophages to low
      environmental pH increased NF-kappa B binding activity in the nucleus, and [2]
      treatment of macrophages with pyrrolidine dithiocarbamate or n-acetyl-leucinyl
      norleucinal, two drugs preventing NF-kappa B translocation to the nucleus,
      canceled low pH-induced nitrite accumulation. The overall mechanism required the
      synthesis of tumor necrosis factor-alpha (TNF-alpha). Indeed, [1] elevated TNF
      alpha bioactivity was observed in the medium of macrophages exposed to pH 7.0,
      and [2] incubation of macrophages with a neutralizing anti-TNF-alpha antibody
      impaired both NF-kappa B activation and nitrite accumulation in response to acid
      challenge. In summary, exposure of macrophages to acidic microenvironment in
      inflammatory lesions leads to the upregulation of iNOS activity through the
      activation of NF-kappa B.

PMID- 9235226
TI  - [Genetic diagnosis of the embryo before implantation].
AB  - The association of recent progress in two initially faraway fields, assisted
      reproductive technology and molecular biology, has made way for the
      preimplantation genetic diagnosis (PGD). For some people this new technique was,
      immediately, considered as an alternative to prenatal diagnosis for couples at
      risk of offspring affected with severe genetic diseases. This technique has the
      advantage of avoiding an eventual abortion and replacing it by an in vitro
      embryos preselection. For others PGD appeared, above all, as matter of new
      eugenic risk. In fact, these excessive hopes and fears have contributed to
      blurring the true current problems of PGD, technical difficulties and still
      limited reliability. While the French law has admitted the principle of PGD use,
      the measures for its application remain to be defined. But this legal
      authorization must recognize that this new technique will be, for a long time, at
      the stage of research, improvement and assessment.

PMID- 9235227
TI  - [Hearing impairment fitting: study of an auditory prosthesis with 7 entirely
      programmable filters].
AB  - We designed a 7-filter digital auditory prosthesis table prototype. For each of
      these filters frequency band width, amplification and compression were
      programmable in order to adapt these parameters to the deaf patient's audiometric
      particularities. We compared the hearing improvement it was possible to obtain
      with our prototype as a function of the number of filters (3, 4 or 7) and their
      frequency band width programmability. We tested 21 patients suffering from middle
      or severe neurosensory hearing loss. This study allows to demonstrate that a 7
      programmable-width-filter strategy seems to be the most appropriate.

PMID- 9235228
TI  - [Preclinical study of the action of a calcium channel blocker during salt load].
AB  - Cardiovascular hypertrophy is a common feature of hypertension, but it is not
      known if this is related only to increased blood pressure or also to non
      hemodynamic factors. Indeed, drug treatment of hypertension with hydralazine does
      reduce blood pressure but not cardiovascular hypertrophy. We used Stroke-prone
      rats (SHRSP) who are sensitive to salt load in order to better characterize the
      action of an antihypertensive agent on salt-dependent vascular hypertrophy and
      change in reactivity of calcium channels. SHRSP were submitted to salt load from
      8 to 14 weeks of age with or without lacidipine, a long acting dihydropyridine.
      We observed that the cardiovascular hypertrophy was attenuated by lacidipine 0.3
      mgkg-1 day-1 which did not change high blood pressure. The action of 1 mgkg-1 day
      1 was higher on hypertrophy but, in addition, it reduced blood pressure. The salt
      related increase in vascular responsiveness to the calcium channel activator Bay
      K 8644 was blunted by lacidipine treatment in both basilar and mesenteric
      arteries. By contrast with basilar artery, in mesenteric artery, this increased
      responsiveness was insensitive to bosentan, an endothelin antagonist but could be
      related to smooth muscle cell depolarization inhibited by lacidipine treatment.
      The present results confirm that lacidipine has blood pressure-independent effect
      on tissue remodeling in hypertension. They show that vascular response to salt is
      heterogeneous among vessels but is equally sensitive to lacidipine.

PMID- 9235229
TI  - [Transmission of rabies virus: importance of the species barrier].
AB  - The authors describe experimental inoculations of different animal species with
      either the wild-type rabies virus or the modified one through in vivo or in vitro
      passages. With these experiments, it was possible to determine the 50% lethal
      dose of these viruses for these species, and to thus quantify the importance of
      the species barrier that opposes, in particular, the transmission of vulpine
      rabies to cats and dogs (respectively 10(5) and 10(6) times more resistant than
      foxes). Studies were also undertaken on the influence of the inoculation route
      and that of serial passages of the virus in vivo or in vitro on the importance of
      resistance to rabies. The epidemiological consequences of the existence of a
      species barrier, its nature and variability, are discussed.

PMID- 9235230
TI  - [Deregulation of homocysteine metabolism and consequences for the vascular
      system].
AB  - The link between vascular disease and elevated homocysteine levels has been
      recognized for more than 30 years, and association with moderately elevated
      levels has been suspected for 20 years. Homocysteine is a sulfhydryl-containing
      amino acid that is formed by the demethylation of methionine. It is normally
      catalysed to cystathionine by cystathionine beta-synthase a pyridoxal phosphate
      dependent enzyme. Homocysteine is also remethylated to methionine by methionine
      synthase, a vitamin B12 dependent enzyme and by methylenetetrahydrofolate
      reductase. Environmental factors such as folate, or vitamin B12, or vitamin B6
      deficiencies and genetic defects such as cystathionine beta-synthase or
      abnormality of methylene-tetrahydrofolate reductase or some vitamin B12
      metabolism defects may contribute to increasing plasma homocysteine levels.
      Normal fasting levels of homocysteine lie within the range 6-16 mumol/l. Apart
      from differences in assay methods, age, sex and nutritional status may affect the
      plasma levels. Though it is now well known that homocysteine is an independent
      risk factor for premature vascular disease, the pathogenesis of homocysteine
      induced vascular damage is, for the most part, unknown. It may be multifactorial,
      including direct homocysteine damage to the endothelium, an enhanced low-density
      lipoprotein peroxidation, an increase of platelet thromboxane A2, or a decrease
      of protein C activation.

PMID- 9235231
TI  - [Angioplasty of three intracranial vertebro-basilar atherosclerotic stenoses].
AB  - This report describes the successful use of transluminal angioplasty for tight
      atherosclerotic stenosis of the basilar or intra-cranial vertebral arteries in
      three patients presenting frequent symptoms that were unresponsive to
      antithrombotic therapy. Excellent clinical results have been obtained with a mean
      follow-up of 24 months. Larger studies are warranted to confirm efficacy and
      safety of this new technic.

PMID- 9235232
TI  - [A request for authorization to use tetrafluoroethane as a propellant gas for
      agents of removal presented in the form of aerosols].

PMID- 9235233
TI  - [Medical update of diverse Codes comprising anti-alcoholism measures].

PMID- 9235234
TI  - [Consequences of carriage for caregivers and for the patient of a possible
      presumption of viral (HIV) contamination of a patient by a caregiver].

PMID- 9235235
TI  - [Health status and standards of life among women in contemporary Russia].
AB  - Female population morbidity in various regions of Russia is as high as 1200 to
      1600 cases per 1000 of women according to consultation rate data. Respiratory and
      circulatory diseases rank first in the morbidity structure. Altogether 42-52% of
      women do not apply to therapeutic and prophylactic institutions during a year.
      Many factors, such as nutrition arrangement, family relations, number of
      children, attitude to life, etc., contribute to health status of a woman and her
      self-assessment of the health status. Morbidity levels of workers and employees
      are different.

PMID- 9235236
TI  - [Family is the foundation for child health].
AB  - Problems of children's health status are discussed in relation to performance by
      a family of its basic functions. Data are presented on a relationship between the
      parameters of children's health status and performance by a family of medical
      function, function of upbringing of children, and function of socialization of
      children. A relationship was established between the level of family functioning
      and stage of development of family vital cycle. The great contribution of a
      mother to treatment and prevention of diseases of children, particularly of
      future mothers, girls, is emphasized.

PMID- 9235237
TI  - [Multi-factorial medico-social study of health and needs of a family].
AB  - The author analyzes the program and methodology of comprehensive sociohygienic
      analysis of family health and requirements of a family in medicosocial care,
      which has been developed and tried. The program has been designed with
      consideration for social, medical, biological, sociological, and other
      characteristics of a family related to family structure, development stage, and
      functioning. Special indexes are offered for assessment of family health and
      structure and levels of family requirements in medicosocial care. Analysis of
      requirements of a young family and a family with an invalid child in health care
      is presented.

PMID- 9235238
TI  - [Use of methods of overall service theory in the organization of therapeutic and
      diagnostic process in the dental care system].
AB  - Consultation rate for emergency dental care in Moscow is analyzed. Consultation
      rate in limited time periods conformed to Poisson's law; this opens vistas for
      applying the theory of overall care in operative planning of emergency dental
      care.

PMID- 9235239
TI  - [Medico-economic rationale of the cost of program for obligatory medical
      insurance and insurance payments].
AB  - Morbidity assessed from consultation rate is one of the most important dynamic
      characteristics of population health. Hence, public health system financing
      should be directly related to the value of total morbidity parameters. A method
      for calculation of an insurance payment is presented, based on the existing
      morbidity. This method permits correction of the sum of an insurance payment with
      consideration for the scope of a local program of obligatory medical insurance.

PMID- 9235240
TI  - [The problems of biomedical ethics development in Russia].

PMID- 9235241
TI  - [Public health status and the course of economic reforms in China].

PMID- 9235242
TI  - [The course of health care reforms in Great Britain: the results and lessons].

PMID- 9235243
TI  - [The founding of the Russian Academy of Medical Sciences].

PMID- 9235245
TI  - [Folk medicine and traditional medicine. Terminology].

PMID- 9235244
TI  - [Russian medicine abroad (1917-1941)].

PMID- 9235246
TI  - [On a problem of multiple causes of death].
AB  - The problem of combined pathology is discussed as exemplified by multiple causes
      of death. The structure of multiple causes of death is analyzed on the basis of
      records on all death cases in the town of Kursk in 1991, a total of 4381. The
      factors taken into consideration are age, sex, classes and various individual
      causes of death; the primary cause and complications are considered, including
      the direct cause of death, and the concomitant conditions. The authors claim that
      their data is a good scientific basis for planning and organization of
      specialized care of the population at the present-day stage of Russian public
      health development.

PMID- 9235247
TI  - [Demographic factors of longevity in Siberia and Far East].
AB  - Longevity indexes LI2 and LI3 (subjects aged 90 and more and 100 and more,
      respectively, among subjects of 60 and older) were compared in all administrative
      units on the basis of results of 1989 Census of the population and data of the
      Central Statistical Office. These values reduce from West to East: LI2 in Western
      Siberia is equal to 8.48/1000, LI3 to 0.45/1000, in Eastern Siberia these values
      are 7.48 and 0.35/1000, in the Far East 5.20 and 0.31/1000, in Russia on the
      whole 9.16 and 0.47/1000, respectively. The territories with relatively high LI2
      values were the Aghinsk Buryat Autonomous Territory (11.42/1000), Yakutia
      (10.79/1000), Altai (9.41/1000).

PMID- 9235248
TI  - [International scientific project: the investigation of pregnancy and childhood].
AB  - ELSPAC, European Longitudinal Study of Pregnancy and Childhood, is the first
      prospective geographically based series of population studies which was designed
      to start during pregnancy and to follow up the cohort of births till the age of 7
      years. This study was initiated at the WHO(EURO) meeting in 1985 in Moscow.
      Various centers in Europe contributed to it in the Czeck Republic, Greece,
      Russia, Slovakia, Spain, United Kingdom, Ukraine. The coordination office of
      ELSPAC is the Division of Paediatric and Perinatal Epidemiology at the Institute
      of Child Health at the University of Bristol, UK. Extensive piloting and
      validating of measures enabled the study to go into the field in selected areas
      at the end of 1990--beginning of 1991. The strength of this survey relies on the
      fact that different correlations in different countries may be useful in
      ascertaining casual relationships and the major thrust of research is to assess
      the impact of psychosocial factors on child health and development.

PMID- 9235249
TI  - [Medical statistical standards of multiple causes of death].
AB  - Presents methodologic approaches to formulation of standard causes of death.
      Based on clinical data, demonstrates examples of standard causes mainly
      responsible for population mortality.

PMID- 9235250
TI  - [The management of resuscitative services in a multi-specialty clinic].
AB  - The authors present the results of research on validation and creation of an
      information mathematical model of resuscitation activity of a multiprofile
      hospital as an example of simulation of operative management of therapeutic and
      diagnostic process in medical structures of all profiles. Profound economic
      transformations in public health system put forward new problems before managers,
      economists, and administrators, who are to develop criteria for assessment of the
      activity of a therapeutic center and a medical worker, to define the scope and
      quality of work performed, to assess financial expenditures which should be
      adequate to the services rendered, to develop systems for continuous follow-up of
      grave patients and monitor the quality of the care rendered, etc. Information
      mathematical simulation of resuscitation activity of a multiprofile hospital will
      help get a detailed characterization of patients and of the activity of
      resuscitation wards, help assess the contribution of physicians and paramedics
      and the level of mastering present-day medical technologies by them.

PMID- 9235251
TI  - [Contemporary medical-demographic processes in Russia].
AB  - Present-day trends in medicodemographic processes in Russia are discussed.
      Changes in population number, sex and age composition, share of capable and
      incapable populations, birth rate and death rate, and natural increment are
      analyzed. Local differences in the levels of natural changes in population
      numbers and in the structure of death causes are substantiated from a demographic
      approach viewpoint. The causes of present-day status of medicodemographic
      characteristics of public health are analyzed with consideration for remote
      effects of war loss, correlations with similar events in world history are
      traced.

PMID- 9235252
TI  - [On activities of sanitary-epidemiological services under new economic
      conditions. The data of sociological study].
AB  - The paper deals with a pressing problem: activities of centers of sanitary and
      epidemiological survey under new economic conditions. The authors discuss
      problems of centralization and adaptation of sanitary epidemiological service
      under present-day economic conditions. They analyze the opinions of heads of
      sanitary epidemiological institutions from various regions of Russia on the
      present-day status of organization and management of the service. Assessment of
      the sources of additional financing of the institutions, of new forms of labor
      organization of departments and specialists, of distribution of additional
      allotments at sanitary epidemiological institutions is presented. Suggestions on
      improvement of the activities of institutions engaged in sanitary epidemiological
      survey under conditions of reformation of sanitary epidemiological service are
      offered.

PMID- 9235253
TI  - [The rising of first aid efficiency to the rural population].
AB  - Latest research revealed a high prevalence of diseases of the ENT organs among
      the rural population, though grave outcomes of such diseases were not recorded.
      Studies of the numbers of ENT specialists in the Urals, chernozem area, and the
      Northern Caucasus showed their inadequate number: 70% of ENT patients were
      treated at central regional hospitals by physicians of other specialization. Half
      of applications for ENT diseases occurs in the evening, night, and morning hours.
      The majority of patients with ENT diseases apply for medical care rather late.
      The number of specialists in ENT diseases should be increased by all means in
      order to render adequate medical care to patients at all stages.

PMID- 9235254
TI  - [Methods of financial analysis for the delivery of dental assistance with the
      obligatory health coverage].
AB  - The authors offer a method for estimation of financing of dental care and
      differentiation of it by various sections. With detailed information at hand, it
      is possible to estimate the cost of a territorial program of obligatory medical
      insurance in dentistry by combining its various sections with consideration for
      the preset scope of dental care and the mean per capita standard of financing and
      the reserve fund.

PMID- 9235255
TI  - [Charity and mercy today: the results of the international symposium in Moscow,
      1992].

PMID- 9235256
TI  - [Metal charity counters of charity-box takings].

PMID- 9235257
TI  - [The scientists of the 2nd Leningrad Medical institute in the years of the Great
      Patriotic War (1941-1945)].

PMID- 9235258
TI  - [The history of physiological institute of Moscow university].

PMID- 9235259
TI  - [The first archiatrist of Russia Doctor Erskin: from the history of Russian
      medicine of the 18th cent].

PMID- 9235260
TI  - [Contemporary social medical problems of the family and issues in medical-social
      services].
AB  - Basing on her experience gained in comprehensive sociohygienic studies, the
      author analyzes present-day medicosocial programs of family health promotion.
      Theoretical conclusions are confirmed by findings of special sociohygienic
      studies. The priority problem of today is, to the author's mind, deterioration of
      the demographic situation caused by reduced reproductive function of a family,
      deterioration of the health status of mothers and their children resulting from
      inadequate performance of the medical function by the family, a higher number of
      induced abortions and divorces, etc. Among approaches to solution of the named
      problem are improvement of medical education of family members, promotion of the
      family principle in public health, development of social service, etc.

PMID- 9235261
TI  - [The structure of childhood disability].
AB  - Characterizes the prevalence and structure of a population of disabled children
      registered in centers for social protection of the population as exemplified by
      Vologda Province. Analyzes the total and primary childhood disability. The
      results will help develop adequate measures aimed at preventing disability and
      for complex medicosocial rehabilitation of disabled children.

PMID- 9235262
TI  - [A health-promoting approach to the study of morbidity with temporary loss of
      work capacity among oil workers in western Siberia].
AB  - Social and economic instability induced a drastic increase in the incidence of
      diseases involving temporary disability among the oilmen of West Siberia in
      recent years. Multifactorial analysis disclosed the principal risk factors
      causing the formation of groups of subjects falling ill frequently and for a long
      time. The structure of risk factors in the multifactorial model of incidence of
      diseases with temporary disability has changed recently, reflecting the situation
      in Russia. The sanological approach to studies of morbidity helps effectively
      develop a system of complex measures aimed at primary prevention, which should be
      adapted to the local conditions. One approach is the creation of screening tests
      to be used in prophylactic check-ups, based on estimation of the threshold
      (critical) number of risk factors.

PMID- 9235263
TI  - [An analysis of a program of sociomedical assessment of the family as a health
      unit and as a patient of the services of primary health and hygiene care].
AB  - The authors for the first time present a program of medicosocial characteristics
      of a family as a patient of primary health care system and of a general
      practitioner/family doctor. It is a complex program consisting of seven blocks,
      including the problems of family methodology, socio-demographic, socio-hygienic,
      material and economic, biomedical, and psychosocial characteristics of a family,
      and medical and social care of a family. The program is assessed from the
      methodological, training, and practical view-points. The authors propose a
      definition of family medicine as a part of the system of knowledge about the
      regularities of family health and the fundamentals of medicosocial care of a
      family. They consider the program of medicosocial assessment of family health a
      priority in the training of physicians and creation of a family medicine system
      and the theory of family health.

PMID- 9235264
TI  - [The characteristics of the psychoemotional background and child rearing in
      families with parents in prison].
AB  - The results of a comprehensive sociohygienic study persuasively prove that a
      family with one parent imprisoned is characterized by a strained psychological
      situation with frequent conflicts due to, primarily, financial and communal
      problems and upbringing of children. The mothers are often cruel to their
      children and pay little attention to them. Moreover, the physical and mental
      development of the overwhelming majority of children in such families is
      decelerated. Hence, study of the life style and health status of children in
      families with parents in prison should become an object of special attention of
      medical workers, teachers, and psychologists.

PMID- 9235265
TI  - [The development of the nongovernmental public health sector in a transitional
      economy].
AB  - The authors compare the development of state and non-state public health. They
      analyze the potentialities of non-state noncommercial medicine and the
      peculiarities of its development. With this aim in view, they consider the forms
      of property and numerous organizational and legal forms of institutions and
      organizations in public health, as well as the mechanisms of quality control
      within the framework of non-state public health.

PMID- 9235266
TI  - [The effect of medical factors on longevity in Russia].
AB  - The authors discuss changes in the priority trends in population health
      protection in Russia; these changes are due to gradual replacement of infectious
      diseases by chronic ones, which are mainly responsible for morbidity and
      mortality. The socioeconomic crisis of the beginning of the 90's involved a
      deterioration of medical care of the population, which led to increase of
      mortality caused by chronic diseases, primarily by diseases of the circulatory
      system. Using the regression methods, the authors analyze the relationships
      between the expected life span, mortality because of diseases of circulation,
      malignant tumors, and traumas, and the medical care of the population, including
      the specialized care. Specificities of these relationships, detected for the
      Leningrad region, indicate the necessity of improving the health measures aimed
      at therapy of chronic disease. The authors offer recommendations for the
      development of public health in Russia with due consideration for the modern
      epidemiological situation.

PMID- 9235267
TI  - [Current problems in price formation in public health].
AB  - Adequate policy of price formation is one condition for effective development of
      public health under conditions of market economy. The authors present the
      fundamentals of price formation in public health under conditions of state
      financing, insurance, and self-support. Price formation should promote the
      activities of public health institutions, aimed at improving the quality of
      medical aid to the population and at the creation of conditions for the welfare
      of medical workers.

PMID- 9235268
TI  - [The conceptual characteristics of developing family rest and physician
      activities at the sanatorium-health resort stage for the rehabilitation of
      different patient contingents].

PMID- 9235269
TI  - [The problem of personnel training].
AB  - The solution of the staff problem arising because of reformation of medical
      education and organization of training of specialists in new fields of medicine,
      required by the market, is a necessary prerequisite for the realization of the
      concept of population health protection. The authors share their experience
      gained in the training of specialists in accordance with the requirements of the
      reform at medical institutes of the Far East.

PMID- 9235270
TI  - [The system for expert assessment of the quality of the medical care in a general
      hospital].

PMID- 9235271
TI  - [An analysis of the activities of hospital institutions on the territorial level
      by using the system of diagnosis-related groups].
AB  - The authors present the results of analysis of the activity of hospitals at one
      territory of Russia making use of a system of Diagnosis Related Groups (DRG).
      Factographic analysis of database for inpatients, based on the DRG typology of
      patients, helped determine the profile of each hospital, group of hospitals, and
      the entire territorial hospital network. The results of analysis permit us to
      define the main profiles of each hospital (or hospital type) and assess its
      actual and potential resources. Such method of analysis, based on the DRG
      typology of patients, may be used for rapid assessment of the activities of
      hospitals in order to determine the trends in possible changes of the hospital
      profile.

PMID- 9235272
TI  - [The problems of budget and insurance medicine].

PMID- 9235273
TI  - [International humanitarian aid in the control of tuberculosis in Voronezh
      Province].
AB  - Presents the experience gained in realization of a program of humanitarian care
      aimed at tuberculosis control in the Voronezh Province of Russia, which was
      organized by the European Community within the framework of UNO-EEC Echo-Rus/B7
      515/93-1806B with participation of the Rudolf Virchow Free University of Berlin.
      Regular bilateral contacts, well-defined purpose of the program, permanent
      supervision from both sides over the fulfillment of plans and conditions of the
      agreement, direct supplies, purchase of equipment and drugs, training of
      personnel, and introduction of the program in practical public health promoted
      its successful realization.

PMID- 9235274
TI  - [The teaching of the pharmaceutical disciplines in the Medical Department of
      Moscow University in the 18th century].

PMID- 9235275
TI  - [The history of the development of insurance medicine in Astrakhan Guberniya].

PMID- 9235276
TI  - [Paul Ehrlich and his contacts with the scientists of Eastern Europe].

PMID- 9235277
TI  - [Zemstvo medicine in Kazakhstan on the edge between the 19th and 20th centuries].

PMID- 9235278
TI  - [The current problems in protecting the health of the population in the oil- and
      gas-producing regions of Tyumen Province].
AB  - A socioeconomic and medicodemographic analysis of modern problems related to
      population health protection in the oil and gas extraction regions of Tyumen
      Province has been carried out under conditions of radical reconstruction of the
      national economy. Changes in the parameters of natural migration of the
      population for each year over a period of 1991 to 1995 are followed up, and
      specific features of the migration processes, effects of socioeconomic and
      medical factors on the health status of individual population groups, rates of
      increment in the number of disabled subjects, and population mortality from
      various causes analyzed. The authors discuss the status of public health services
      and offer measures for improving their efficacy in the above regions.

PMID- 9235279
TI  - [Current method for pregnancy termination with prostaglandins in the 2nd and 3rd
      trimester].

PMID- 9235280
TI  - [Ultrasound diagnosis of periventricular leukomalacia].
AB  - Periventricular leucomalacia (PVL) is the most common form of hypoxemic brain
      damage in infants. In PVL, there is usually a preceding history of asphyxia or
      hypoxia. This results in hypoxic-ischaemic damage to the region of the brain
      around the lateral ventricles, a particularly vulnerable area as it is in a
      border zone between arterial supplies. PVL is usually first recognised as an
      echodense heterogenic flare in the anterior and posterior periventricular areas
      on brain ultrasound scan. This must clearly be differentiated from the typical
      halo seen in newborns. The formation of pseudocystic periventricular lesions is
      typically seen after 2 weeks. Thereafter, PVL is characterized by ventricular
      asymmetry with irregular walls or by cerebral atrophy. Age-specific neurological
      ultrasound findings are rarely seen in patients with PVL. As these individual
      developmental stages of PVL cannot always be found by ultrasound scan, the
      following criteria for diagnosis are recommended: Increased intense and
      heterogenic echodense areas followed by a breaking up of these echodense areas in
      the anterior and posterior periventricular regions on brain ultrasound scan.
      Multiple and thick-walled, initially non-communicating periventricular
      pseudocysts. Persistent typical asymmetrical dilatation of ventricles with
      irregular and blurred ventricular walls.

PMID- 9235281
TI  - [Perinatal management of children with prenatal diagnosis of congenital heart
      defects].
AB  - During the recent years an increasing number of patients with congenital heart
      disease has been diagnosed prenatally by fetal echocardiography. The purpose of
      this study was to answer the question, which consequences will result from this
      prenatal information concerning the timing and mode of delivery as well as the
      neonatal treatment in these patients. From 12/1990 until 10/1994 21 neonates were
      treated in our center who had prenatal diagnosis of congenital cardiac
      malformation. In none of these patients we decided to change the timing or mode
      of delivery based on the hemodynamic findings of the cardiac malformation.
      Postnatally there was no evidence that this mode of delivery had a negative
      impact on the outcome in one of these neonates. All children, however, were
      delivered in a perinatal centre providing optimal perinatal care and early
      involvement of a pediatric cardiologist in the postnatal treatment. The perinatal
      treatment of patients with isolated ventricular or atrioventricular septal
      defects did not require specific intensive care measurements. On the other hand
      the majority of neonates with left heart, right heart or complex cardiac
      malformations required early intubation (81%), mechanical ventilation and
      intravenous administration of prostaglandin E1 (69%). Due to the prenatal
      diagnosis these measures were started before the adverse effects of ductal
      closure could lead to a hemodynamic deterioration in these patients. Despite this
      treatment 11/21 patients (52%) died in the neonatal period or in early infancy.
      Based on our experience we do not propose a change in the mode of delivery in the
      majority of children with prenatal diagnosis of congenital cardiac malformations.
      For further improvement in the perinatal treatment of children with congenital
      heart disease a close cooperation of gynecologists, neonatologists and pediatric
      cardiologists as well as concentration of those patients to perinatal centres
      will be necessary.

PMID- 9235282
TI  - [The macrosomic neonate: incidence, early morbidity and legal aspects. An
      analysis of the Hessia perinatal study].
AB  - In the past 13 years in Hessian Hospitals there is an 20% increase of newborn
      with a birthweight range between 4000-4499 g and a 17% increase of newborns weigh
      more than 4499 g. The incidence in the first weight group increases from 7.8% to
      9.3% and in the second weight group from 1.3% to 1.53%. Since 1990 the decrease
      in the incidence of obstetrics traumas in single macrosomic newborns in vertex
      presentation will be missed, although there was an decrease from 1982 to 1990.
      There is a statistically significant higher incidence of injuries in the weight
      group above 4499 g than in the both weight groups below 4500 g. In 13 years the
      rate of primary Caesarean section only increases in the weight group in the range
      from 2500 to 3399 g whereas the secondary Caesarean section rate rises in all 3
      weight groups. The ratio of an acidosis (ph < 7.10) after vaginal delivery is not
      different between these 3 newborn groups. After secondary Caesarean section the
      mean acidosis rate of 5 years (1990-1994) is 2.3% in the normal weight group and
      1.5% in the macrosomic newborns. There is no difference in the acidosis rate in
      the macrosomic newborn groups between vaginal an secondary abdominal delivery. In
      our opinion the data are no argument for a primary Caesarean section in the
      weight group above 4499 g. The higher rate of secondary caesarean section and the
      higher transfer rate of the macrosomic newborns with a birthweight above 4499 g
      into a neonatal unit represents an elevated perinatal risk. Therefore it will be
      recommended to send the pregnant women before the beginning of labour in a
      special obstetrics department in case of estimated birthweight higher than 4499 g
      according to sonographic examination.

PMID- 9235283
TI  - [Surviving mono-amniotic twins. Case report and review of the literature].
AB  - The authors describe a case with double perinatal survival of a monoamniotic twin
      pregnancy and give a survey on the literature regarding this rare and riskful
      kind of twinning. The importance of accurate antenatal diagnosis, intensive fetal
      surveillance and operative delivery is discussed.

PMID- 9235284
TI  - [German-Austrian Society of Neonatology and Pediatric Intensive Care Medicine].

PMID- 9235285
TI  - [Partial premature abruptio placentae].

PMID- 9235287
TI  - All-ceramic crown systems: clinical research versus observation in supporting
      claims.

PMID- 9235286
TI  - [Ricinus oil for labor induction].

PMID- 9235288
TI  - Essential biochemical design features of the fuel-sensing system in pancreatic
      beta-cells.
AB  - The beta-cells of the pancreas control the blood levels of glucose and other
      nutrients by secreting insulin. They sense blood nutrient levels not by using a
      classical receptor-signaling system, but by detecting the products of nutrient
      metabolism. Mutations in this pathway can cause diabetes or hypoglycemia.

PMID- 9235289
TI  - TeleMed 96. Medicine on the SuperHighway. Proceedings of an international
      conference on telemedicine and telecare. London, United Kingdom, 13-14 November
      1996.

PMID- 9235290
TI  - 5th Annual Congress on Women's Health. Washington, DC, June 23-25, 1997.
      Abstracts.

PMID- 9235291
TI  - After sumatriptan-the flood.

PMID- 9235293
TI  - Cytokines in the Brain: Neuropathological Aspects. Proceedings of a meeting.
      Saint-Jean-de-Luz, France, April 26-28, 1996.

PMID- 9235292
TI  - The Society of Cardiac Angiography and Interventions 20th annual meeting.
      Scottsdale, Arizona, May 13-17, 1997. Abstracts.

PMID- 9235294
TI  - Proceedings of the 2nd Siena 2-D Electrophoresis Meeting. Siena, Italy, September
      16-18, 1996.

PMID- 9235295
TI  - Heart transplantation in patients over 54 years of age.

PMID- 9235296
TI  - Is there a future for PET in oncology?

PMID- 9235297
TI  - Wash-out kinetics of 99mTc-MIBI and the scintigraphic determination of PGP
      expression.

PMID- 9235298
TI  - [Family medicine--rediscovered as a specialty area. General practice moves
      specialty back into central focus].
AB  - Family medicine remains an integral part of the GP's responsibilities. To a large
      extent, the doctor in general practice still provides care not solely to
      individual patients, but often to several members of the same family. Functions
      and obligations, together with the dynamics and problems, of the family are
      determinants of the health and illnesses of family members, and the GP needs to
      understand and be aware of this. Also of value to the physician providing primary
      medical care is a knowledge of the various different types--possibly even
      pathogenic--of family.

PMID- 9235299
TI  - [Is the general practitioner still the family physician today?].
AB  - As the data collected in a survey we conducted show, a major part of the modern
      general practitioner's work continues to be in the field of family medicine. This
      fact is also confirmed by the results of other surveys of general practice today.
      Patients still appreciate their GPs as a source of good medical care and
      counseling for the whole family. Our own study has shown that most patients would
      even like to see an expansion of the GP's counseling activities. The duration of
      the doctor-family relationship extends over many years, and is frequently longer
      than a decade.

PMID- 9235300
TI  - [Patient environment as the domain of the family physician. Organ-specific
      medicine is only one side of the issue].

PMID- 9235301
TI  - [Current insulin therapy. Treatment with new short-acting and retard insulin
      analogs].
AB  - Intensified insulin therapy of type I diabetics can now be rendered more patient
      friendly through the use of rapid-action insulin. Thus, for example, the rapid
      absorption of the monomeric lispro insulin (Humalog) out of the subcutaneous
      fatty tissue obviates the need to observe a delay between injection and meal, and
      the changed kinetics of action reduce the danger of postprandial episodes of
      hypoglycemia. In addition to practice-relevant hints on the use of these new
      short-acting insulins in intensified insulin therapy, this short article reviews
      the current state of the development of a new long-acting insulin that is shortly
      to be tested in an international multi-center phase III study.

PMID- 9235302
TI  - [From human insulin to designer insulin. Why insulin analogs?].

PMID- 9235303
TI  - [Diagnosis with joint puncture. 5. "Diagnostic strategies in rheumatology"].

PMID- 9235304
TI  - [Statistical significance should not be confused with clinical relevance! Correct
      tests guarantee reliability, position of the editors].

PMID- 9235305
TI  - [Improvement in ischemia-reperfusion damage to the liver. Blockade of endothelin
      receptors inhibits vasoconstriction].

PMID- 9235306
TI  - [Lamivudine resistance impedes hepatitis B therapy].

PMID- 9235307
TI  - [Reliability of family reports of illness anamnesis of schizophrenic patients].
AB  - Because a valid psychiatric history is difficult to obtain from an acute
      psychotic patient, particularly upon first admission, information given by
      important others is necessary for diagnostic classification, but the validity of
      this data must be examined. Within the ABC Schizophrenia Study, the onset and
      early course of schizophrenia was assessed from 171 post-psychotic first
      admissions and their close relatives. High agreement was found for substance
      abuse, self-destructive behaviour, paranoid delusion and social role deficits.
      Agreement was low for unspecific symptoms like depression, anxiety, problems with
      concentration or sleep. Due to a lack of sensitivity of the relatives' reports,
      agreement was also low for formal thought and perceptual disorders and
      derealization. A second study with 30 patients with schizophrenia and with 2 or
      more relatives for each case (n = 69) demonstrated that the quality of relatives'
      reports depends primarily on the relative's image of the patient (e.g., perceived
      dominance) and on the relative's attributions about the cause of the disease.
      Close and long contact tends to impair the quality of reports. Again, the
      observation of different symptoms is influenced differently by these factors.

PMID- 9235308
TI  - [Diagnostic and follow-up typological characteristics of early schizophrenia].
AB  - Schizophrenic psychoses with early onset (< or = 10) are very rare; they occur in
      approx. 0.5-1% of the total number of patients. Long-term research with
      sufficiently long observation periods may be able to answer the question whether
      there is a nosological continuity between early-onset schizophrenia and
      schizophrenic psychoses in adults. We report on the results of a study on 13
      patients with onset at the age of 10 years or earlier (7 girls, 6 boys) with an
      average duration of illness of 36.1 years (SD = 10.2 years). 3 patients had
      deceased in the meantime, one patient could not be reached by mail. 9 of the
      original 13 patients could be examined during the second follow-up by the same
      interviewer (on the average 27 years after the first follow-up). In 5 children
      the onset was acute (less than one week), in 8 children insidious (more than 4
      weeks). Among the 5 patients with acute onset of childhood psychoses the positive
      PANSS-type (60%) predominated, in the 8 patients with at first barely perceptible
      beginning, the negative PANSS-type (45%) prevailed. In respect of the diagnostic
      division into subcategories, we found a remarkably large variability: At the
      beginning the disorganised type, at the first follow-up the paranoid, and at the
      second follow-up the catatonic and the disorganised type were diagnosed most
      frequently by 4 independent raters. The evaluation of the whole course shows that
      the incidence of the paranoid type was most frequent. Clear positive-productive
      psychotic symptoms occurred very early in our patients, i.e. already at the age
      of 7 years. On the whole, 77% of the patients showed positive symptoms from the
      beginning of psychotic breakdown; more than half of them had hallucinations from
      the beginning. This is contrary of the current opinion that childhood-onset
      schizophrenia begins predominantly with negative symptoms. However, at the
      beginning of insidious courses, negative symptoms prevail. The prognosis for the
      8 insidious courses on the whole was unfavourable (only one full remission, one
      partial remission, the rest poor or very poor remissions). No connection between
      the total diagnosis (subtype) and the remission grade was seen.

PMID- 9235309
TI  - [Mortality of patients with functional psychiatric illnesses during inpatient
      treatment].
AB  - Data from 7 psychiatric hospitals with defined catchment areas were analysed.
      8927 episodes of treatment in patients with functional psychiatric disorder were
      recorded within 30 months (mean age 43.4 +/- 16.6 years; 41.2% male patients).
      During their stay in hospital 51 patients died, 31 from natural causes and 20 by
      suicide, compared to 12 deaths expected from the mortality rates of the general
      population. Standardised mortality ratios (SMRs) were calculated for the
      different diagnostic and age groups. In the whole population mortality from all
      causes (SMR 4.27, p < 0.001), as well as from natural causes (SMR 2.6 < 0.01)
      were significantly raised. Risks were highest in patients with schizophrenia (SMR
      for all causes of death 6.6, p < 0.001). Mortality from natural causes was
      significantly elevated in schizophrenia and related disorders. Furthermore, a
      high level of excess mortality mainly due to suicide was established in patients
      aged under 45 years (SMR 12.2, p < 0.001). Cardiovascular disorders were the most
      frequent causes of natural death. Our data substantiate a significantly elevated
      mortality risk due to natural and unnatural death of patients hospitalised for
      acute mental illness. Although the causative factors have not yet been fully
      clarified, prophylactic measures with regard to medical care as well as suicide
      prevention should be intensified in psychiatric hospitals.

PMID- 9235310
TI  - [Neuroradiologic activation studies of cerebral organization of language
      capacities. A review of the literature].
AB  - Models on the cerebral organisation of speech and language capacities are
      predominantly based on lesion studies. Neuroradiological activation methods using
      positron emission or magnetic resonance tomography provide a further means to
      investigate brain-behaviour relationships. The present paper reviews the
      available data obtained with functional imaging during speech and language tasks.
      The classical connectionist model suggests several distinct language centres
      within the perisylvian area of the dominant hemisphere. Especially the processing
      of complex verbal stimuli yields haemodynamic and metabolic reactions outside
      this area. At least partially, these extrasylvian foci might reflect
      paralinguistic functions such as motivational or attentional aspects of speech
      production, or the processing of emotions conveyed by verbal utterances. As far
      as linguistic capacities are concerned, functional imagery has yielded two
      results which extend the classical connectionist model of speech and language
      functions: (a) the medial part of the occipital lobe of the dominant hemisphere
      seems to comprise representations of visual word forms; (b) word generation
      yields activation of cerebellar structures. In contrast to the classical
      connectionist model, reading did not cause reactions of the angular region of the
      left hemisphere. Furthermore, phonological and semantic processing of verbal
      stimuli include the anterior perisylvian language zones. The interpretation of
      discrepancies between data derived from lesion studies and those obtained with
      functional imaging is still unsettled. First of all, rapid cognitive processes do
      not necessarily give rise to a detectable significant haemodynamic or metabolic
      response. Secondly, highly automatised language processes such as inner speech
      are difficult to control.

PMID- 9235311
TI  - [Post-traumatic stress disorder. New research findings].
AB  - This article reviews recent research results on posttraumatic stress disorder
      (PTSD). Epidemiological studies show that PTSD is a common disorder within the
      normal population with a high degree of chronic courses. Degree of severity as
      well as dissociative symptoms during the traumatic event seem to have an impact
      on course and outcome of PTSD. A genetic disposition, familial psychopathology
      and premorbid personality traits as background variables seem to have an
      influence on the development of PTSD whereas coping strategies, as well as social
      support, modify the course of the disease. The investigation of biological
      parameters refers to the hypothalamic-pituitary-adrenal-axis system, provocation
      studies, psychophysiological studies, and studies of the endogenous opiate
      system. In regard to therapy studies only those with a randomised allocation to
      two different therapies as well as with a control group without therapy or a
      waiting list group are considered, using the DSM-III or DSM-III-R diagnostic
      criteria for PtSD. Five pharmacological studies could show a positive effect by
      antidepressants. Six behaviour therapy studies (two systematic desensitisation
      and four flioding) produced an improvement of PTSD symptomatology. The
      pathogenetic models discussed here are memory imprinting, kindling, dysregulation
      of the opioid neuromodulation, classical conditioning and disturbed cognitive
      schemas, which reflect as single models only a facet of the pathogenesis.

PMID- 9235312
TI  - [Neuroleptic malignant syndrome from treatment with antidepressives].
AB  - The neuroleptic malignant syndrome (NMS) is a rare complication in the treatment
      of neuroleptics. The pathophysiology is not fully known. A dopaminergic
      transmission block in the basal ganglia and the hypothalamus is thought to be the
      pathophysiological mechanism of NMS. There are some findings against the single
      role of dopamine receptor blockade: NMS is rare under neuroleptic treatment,
      although a strong dopamine receptor blockade is found even with a low dosis of
      neuroleptics. NMS can develop even after longterm treatment with neuroleptics and
      is not improved by dopamine agonists within the expected period. NMS may even
      develop when neuroleptics are reduced. Several cases have been reported of NMS
      precipitated by medication without a direct effect on dopaminergic system. Only
      rare case reports describe NMS under antidepressants. We report on all cases of
      NMS associated with antidepressants and present the different pathophysiological
      hypotheses on the precipitation of NMS.

PMID- 9235313
TI  - [Neuroleptic-induced supersensitivity].
AB  - Psychopharmacological agents may cause changes in receptor sensitivity. Long-term
      treatment with high doses of neuroleptics has been shown to lead to
      supersensitivity of postsynaptic dopamine and noradrenaline receptors. Receptor
      supersensitivity is seen more frequently with neuroleptics known to have a high
      receptor affinity. The mechanism by which psychoses of the supersensitivity type
      work is presented and is illustrated by two case reports. Possible
      pathophysiological mechanisms for the emergence of these psychoses and
      implications for the treatment of patients suffering from them are discussed.

PMID- 9235314
TI  - [Frontal-subcortical neuronal circuits].
AB  - Recent findings on frontal and subcortical circuitry provide an uniform and
      integral view of numerous neurological and psychiatric disorders. Frontal
      cortical areas, the basal ganglia and the thalamus are linked in parallel
      circuits, which can be related to specific mental and motor functions and
      pathologies. In particular, five such circuits can be distinguished: (1) motor,
      (2) oculomotor, (3) dorsolateral-pre-frontal, (4) lateral orbitofrontal, and (5)
      mediofrontal limbic. The anatomy of these circuits as well as the involved
      neurotransmitters provide a comprehensive framework for understanding the
      symptoms of neurological diseases such as frontal lobe infarctions, Parkinson's,
      Huntington's, and Binswanger's disease, as well as psychiatric diseases such as
      schizophrenic, affective, and obsessive-compulsive disorder.

PMID- 9235315
TI  - [The symptomology of akathisia].
AB  - The phenomenon of akathisia is characterised by a subjective feeling of inner
      agitation accompanied by general motoric restlessness, which particularly affects
      the legs. It is mainly the inner agitation from which the patients suffer, but
      which they often cannot describe in any detail. The psychopathology of akathisia
      is presented in a case report, the emphasis being on a detailed description of
      inner agitation. Furthermore, motor, affective and cognitive symptoms of
      akathisia are pointed out. Finally, differential diagnosis of akathisia and
      standardised scales for assessment are discussed.

PMID- 9235316
TI  - [Epilepsy in the very old].
AB  - Epilepsy ist the third most common neurological disease of the elderly. In the
      elderly the incidence is higher than in childhood and adolescence.
      Cerebrovascular diseases are in 50% of the cases the most common cause for a
      seizure beyond the age of sixty. The importance of neoplasias is often
      overestimated. The risk for a renewed seizure after a first seizure is higher in
      the senium than in youth. Furthermore, the incidence of seizure-related injuries
      is increased in the elderly and therefore, anticonvulsive therapy must be started
      early with guaranteed compliance. With regard to therapy, the altered
      pharmacokinetics in senium must be considered. The drug of first choice is
      carbamazepine. If a monotherapy with carbamazepine, phenytoin or valproate does
      not control the seizures a combination with one of the new antiepileptic drugs
      must be initiated. Due to their pharmacokinetic characteristics, the new drugs
      such as vigabatrin, gabapentin and lamotrigine-are specially suitable in the
      therapy of elderly patients. In case of undesirable side effects, monotherapy
      with one of the new anti-convulsants ought to be considered.

PMID- 9235317
TI  - [Message from the President of the Society].

PMID- 9235318
TI  - [Follow-up results of intracardiac repair of total transposition of great
      vessels].

PMID- 9235319
TI  - [Follow-up results of arterial switching operation of total transposition of
      great vessels].

PMID- 9235320
TI  - [Follow-up results of Jatene surgery of total transposition of great vessels].

PMID- 9235321
TI  - [Postoperative follow-up results of total transposition of great vessels].

PMID- 9235322
TI  - [Hazard developing during the follow-up after reparative surgery for complete
      transposition of great arteries].

PMID- 9235323
TI  - [Keypoints in improving the results of emergency surgery of aneurysm of the
      thoracic aorta--evaluation of therapeutic results].

PMID- 9235324
TI  - [Management of emergency surgery of aneurysm of thoracic aorta and postoperative
      results].

PMID- 9235325
TI  - [Emergency surgery of aneurysm of the thoracic aorta: for prediction of surgical
      results based on preoperative factors and determination of therapeutic policies].

PMID- 9235326
TI  - [Postoperative results of emergency surgery of aneurysm of the thoracic aorta
      based on the site of replacement and etiology].

PMID- 9235327
TI  - [Results and keypoints in emergency surgery of true and dissecting aortic
      aneurysms].

PMID- 9235328
TI  - [Management of emergency surgery of aneurysm of the thoracic aorta and
      postoperative results--evaluation of the causes of death and surgical methods].

PMID- 9235329
TI  - [Evaluation of the effects of pre-operative hyperthermia, chemotherapy, and
      radiotherapy (HCR) on malignant esophageal cancer].

PMID- 9235330
TI  - [Combined chemo- and radio-therapy to improve the therapeutic results for highly
      malignant esophageal cancer].

PMID- 9235331
TI  - [Design to improve the therapeutic results in A3 esophageal cancer --combined
      resection and neoadjuvant chemotherapy].

PMID- 9235332
TI  - [Results of multimodal treatment combined with remote after-loading system (RALS)
      for malignant esophageal cancer].

PMID- 9235333
TI  - [Indication for surgical therapy and innovation in surgical procedures for cancer
      of thoracic esophagus with marked involvement of the cervical upper mediastinum].

PMID- 9235334
TI  - [Evaluation of direct administration of DDS-CDDP into the mediastinum for
      malignant esophageal cancer].

PMID- 9235335
TI  - [Comparison of cases with or without mediastinal lymph node excision in cases
      with negative findings in mediastinoscopy: evaluation based on prognosis].

PMID- 9235336
TI  - [Significance of preoperative mediastinoscopic examination at lymph node
      dissection].

PMID- 9235338
TI  - [Advantages and disadvantages of systematically extended lymph node excision at
      surgery of non-small-cell carcinoma of the lung].

PMID- 9235337
TI  - [Possibility for rational mediastinal dissection in non-small-cell carcinoma of
      the lung].

PMID- 9235339
TI  - [Advantages and disadvantages of lymph node dissection in surgery of non-small
      cell carcinoma of the lung--with special reference to a study of cases of N0
      pathologic N2].

PMID- 9235340
TI  - [Is lymph node dissection necessary in small, non-small-cell carcinoma of the
      lung occurring at the peripheral region?].

PMID- 9235341
TI  - [One-stage bilateral lung volume reduction surgery with median sternal incision
      for diffuse pulmonary emphysema].

PMID- 9235342
TI  - [Evaluation of thoracoscopic laser treatment and volume reduction surgery of
      diffuse pulmonary emphysema].

PMID- 9235343
TI  - [Comparison of surgical therapy (pneumonectomy and thoracoscopic stapled lung
      reduction) in pulmonary emphysema].

PMID- 9235344
TI  - [Efficacy of thoracoscopic pulmonary reconstruction in diffuse pulmonary
      emphysema--selection of surgical procedures based on Xe SPECT findings].

PMID- 9235345
TI  - [Volume reduction surgery for patients with severe pulmonary emphysema].

PMID- 9235346
TI  - [From excision of giant emphysematous lung cysts (giant bullae) to lung volume
      reduction surgery].

PMID- 9235347
TI  - [Graft selection in coronary artery bypass graft (CABG)].

PMID- 9235348
TI  - [Efficacy of the left coronary bypass procedure using bilateral internal thoracic
      arteries].

PMID- 9235349
TI  - [Efficacy and keypoints in arterial graft surgery of coronary disease with
      involvement of 3 coronary branches--does the procedure improve over the follow-up
      results of single ITA to the left anterior descending limb?].

PMID- 9235350
TI  - [Graft selection in coronary artery bypass surgery in the aged].

PMID- 9235351
TI  - [Possibility of improving postoperative QOL by selecting the gastroepiploic
      artery as a graft in coronary artery bypass].

PMID- 9235352
TI  - [Evaluation of revascularization of the circumflex branch by in situ RITA].

PMID- 9235353
TI  - [Early results of coronary artery bypass using a radial artery bypass].

PMID- 9235354
TI  - [Genetic analysis and clinical significance of heterotopic hCGbeta production in
      lung cancer].

PMID- 9235355
TI  - [Expression of metastasis-related genes in the samples collected at surgery of
      lung cancer and its relationship with prognosis].

PMID- 9235356
TI  - [VEGF121 expression and angioneogenesis in lung cancer].

PMID- 9235357
TI  - [KAI1/CD82 and ME491/CD63 expression in non-small-cell carcinoma of the lung and
      prognosis].

PMID- 9235358
TI  - [Analysis of nuclear matrix protein in human lung cancer cells].

PMID- 9235359
TI  - [Molecular biological diagnosis of non-small-cell carcinoma of the lung and its
      application to therapy].

PMID- 9235360
TI  - [Selection of surgical procedures in heart valve diseases based on follow-up
      results: comparative evaluation of valve replacement and valvoplasty].

PMID- 9235361
TI  - [Valve replacement and valvoplasty in combined valvular diseases].

PMID- 9235362
TI  - [Surgical methods for mitral valve reflux due to valvular prolapse and
      comparative evaluation of the follow-up results].

PMID- 9235363
TI  - [Outcome of surgical treatment of acquired mitral valve diseases: efficacy of
      preservation or reconstruction of the chordae tendineae and mitral valve
      replacement].

PMID- 9235364
TI  - [Trends in surgery of heart valve diseases and recommendation of valvoplasty in
      aortic and mitral valve insufficiencies].

PMID- 9235365
TI  - How far do we go to protect patient welfare? Breaching unit staff confidentiality
      and trust.

PMID- 9235367
TI  - Isolated radial head dislocation in an adult: case report and review of the
      literature.

PMID- 9235366
TI  - Gene expression of albumin and liver-specific nuclear transcription factors in
      liver of protein-deprived rats.
AB  - Protein-energy malnutrition causes hypoalbuminemia. Recent work has suggested
      that this may be partly due to decreased transcription of the albumin gene. This
      study examined the role of cis-acting and transacting elements of the albumin
      gene during protein deprivation. Male 7-wk-old Donryu rats were fed a protein
      free diet (0% casein diet) for 10 d or given restricted (pair-fed control) or
      free access (freely fed control) to a 25% casein diet. Serum albumin
      concentrations were significantly lower in the protein-deprived rats (29 +/- 1
      g/L) than in the pair-fed controls (42 +/- 3 g/L) or the freely fed controls (45
      +/- 3 g/L). The albumin mRNA level was also significantly lower in livers of
      protein-deprived rats (36% of pair-fed control). However, gel mobility shift
      analysis using liver nuclear extracts did not show any significant difference
      between the protein-deprived rats and the pair-fed controls in the binding
      activity to the B and D sites of the albumin promoter. Furthermore, gel mobility
      shift-Western blot analysis showed no significant difference between the two
      groups in the protein levels of nuclear transcription factors binding to the D
      sites. The amounts of mRNA of hepatocyte nuclear factor-1 binding to the B site
      were not significantly different between these two groups. These results suggest
      that the proximal promoter region may not play a major role in the down
      regulation of the albumin gene during protein deprivation.

PMID- 9235368
TI  - Isolated radial head dislocation in an adult: case report and review of the
      literature.

PMID- 9235369
TI  - Isolated radial head dislocation in an adult: case report and review of the
      literature.

PMID- 9235370
TI  - Report of the Fifth European Meeting on Psychosocial Aspects of Genetics.

PMID- 9235371
TI  - Consensus conference on HIV/AIDS and drug abuse treatment. Maryland, March 14-15,
      1995.

PMID- 9235372
TI  - [Subtotal radical resection and primary reconstruction in breast cancer].
AB  - The authors present information on 44 patients with local breast carcinoma
      (Stages II and III) who were treated by a new type of operation in the form of
      radical subtotal resection of the breast and one-stage reconstruction without the
      use of endoprostheses. The authors describe some scientific and technical
      problems of the performance of these complicated surgical interventions. In
      future these operations may become operations of choice for a certain category of
      patients because they solve both therapeutic and rehabilitation problems.

PMID- 9235373
TI  - [Results of pneumonectomy with resection of the tracheal bifurcation].
AB  - The results of pneumonectomy with resection of tracheal bifurcation in 779
      patients reported by 54 authors for the period of 44 years are reviewed. The
      analysis of all the data showed that this operation remains one of the most
      dangerous and rare surgical procedures. Lethality in total bifurcation resection
      averaged 24.3% and in partial resection--10.2%. Because of lack of experience
      there is no distinct indications for the operation in cancer patients. The
      authors have performed 111 pneumonectomies with bifurcation resection (39 with
      circulatory resection) with lethality of 2.7% and 5-year survival of 25%. This
      proves the ability of updated surgical technique to decrease surgical risk and
      extend indications for surgery of local cancer.

PMID- 9235374
TI  - [Current status of gastric cancer morbidity].
AB  - Gastric cancer is one of the most common diseases in patients over 70 years of
      age. It makes 14.4% of all malignant tumours, 15.7%--if oncohaematological cases
      are not included, and 19.8%--if oncohaematological cases and skin basaliomas are
      not considered. Most frequently the 1st stage of cancer was found in patients
      over 70 years of age (41.8%). The 4th stage of cancer is most commonly detected
      in patients of the oldest age group (34.5%). The program for early detection
      makes it possible to increase significantly timely diagnosis of gastric cancer
      (up to 80% in stages I and II). The screening program provides the detection of
      early stages of gastric cancer in 40.6% of the patients with the 1st stage of
      gastric cancer. 5-year survival is 30.2%, the corrected rate--40.3%. The rates of
      5-year survival (both--observed and corrected) are the highest in patients with
      the 1st stage of the disease. The 5-year survival rate in patients aged 50-59
      years is 65.5%; whereas in patients over 70--16.0% and 27.7% (observed and
      corrected, respectively).

PMID- 9235375
TI  - [Nonepithelial tumors of the stomach].
AB  - 816 patients were operated on because of gastric tumors; in 55 cases they were
      nonepithelial. Lymphomas have been found in 18 cases, glomus tumors--in 13 cases,
      leiomyomas, neurinomas and lipomas--in 11 cases, carcinoid--in 7 cases, aberrant
      pancreas--in 5 cases, gastric wall cyst--in 1 case. In half of the cases tumors
      were malignant. The preoperative diagnosis was absolutely correct in 30.9%
      patients and in 61% of cases with gastric lymphomas. All patients with
      nonepithelial gastric tumors should be operated on. In gastric lymphoma
      extirpation of the stomach is the operation of choice. In nonmalignant tumors
      with infiltrative growth and a size not more than 3 cm a stomach resection should
      be done, in a smaller size--a wedge resection and in subserous small tumors its
      enucleation, in submucous variant--endoscopic removal is possible.

PMID- 9235376
TI  - [Intravenous tumor invasion in renal cancer].
AB  - Intravenous tumor invasion occurred in 84 out of 600 patients who had been
      operated on for carcinoma of the kidney. The inferior vena cava was thrombosed by
      a tumor in 54 patients. Ultrasonic examination, computed tomography, and
      venocavography were used in establishing the diagnosis of intravenous invasion.
      It is stressed that information on the upper border of the thrombus in the
      inferior vena cava must be obtained before the operation, and that in block on
      the inferior cavogram transatrial venocavography is absolutely indicated. The
      presence of absence of growth of intracaval tumor masses into the wall of the
      inferior vena cava is an important moment determining peculiarities of the
      operation. In the authors experience such invasion was encountered in 30% of
      patients. Fifty-two patients had subdiaphragmatic thrombosis of the inferior vena
      cava and 2 patients had supradiaphragmatic thrombosis. In addition to radical
      nephrectomy, 28 patients underwent resection of the lateral surface of vena cava
      inferior, 17--thrombectomy from vena cava inferior, and 8--resection of a segment
      of this vein. Postoperative lethality was 9.5%, 5-year survival was 40.8%. It was
      found that venous invasion without growth of the tumor into the fibrous capsule
      of the kidney and without lymphogenous and distant metastases has no negative
      effect on the prognosis if the tumor masses had been removed completely from vena
      cava inferior. The authors believe operations on patients with renal carcinoma
      and venous tumor invasion in stages T2N0M0, T3N0M0 and T2-3N1-2M0 to be
      advisable.

PMID- 9235377
TI  - [Ozone therapy of diffuse peritonitis in the early postoperative period].
AB  - The study of the use of ozone-containing solutions in 40 experimental animals and
      in 58 patients with diffuse purulent peritonitis revealed their marked detoxicant
      effect that manifested with early decrease of ESR, leucocytosis, plasma
      concentration of bilirubin and medium-size molecules, and microbes. Lethality in
      the experimental and control group were 5.2 and 16.6% respectively.

PMID- 9235378
TI  - [Preoperative care and anesthesia in patients with diffuse suppurative
      peritonitis].

PMID- 9235379
TI  - [Comparative aspects of the diagnosis of diseases of organs of the hepato
      pancreatico-duodenal zone].
AB  - The results of investigations the hepato-pancreatico-duodenal organs are
      analysed. High diagnostic effectiveness of the ultrasound examination in acute
      cholecystitis (95.5%) is demonstrated. In chronic calculous cholecystitis and in
      choledocholithiasis the ultrasound examination appeared to be accurate in 97.0%
      and 84.2% of cases respectively. Retrograde cholangiopancreatography was the most
      informative method for detection of the concrements in choledochus (effective in
      94.4% of the cases). The diagnostic effectiveness of the ultrasound examination
      and laparoscopy in detection of mechanical jaundice and acute pancreatitis are
      considered to be equal. Ultrasound examination, retrograde
      cholangiopancreatography, laparoscopy appeared to be the most accurate and
      informative methods in diagnosis of the diseases of the organs of hepato
      pancreatico-duodenal zone. The role of the X-ray examination decreased. At the
      same time the significance and reliability of intraoperative cholangiography has
      been stressed.

PMID- 9235381
TI  - [Wounds and traumas of the chest].
AB  - The results of the treatment of 2332 patients with wounds and closed chest
      injuries have been analysed and basic mechanisms of life-threatening conditions
      development determined. Specific features of the most common variants of chest
      damages as well as the role of various diagnostic and therapeutic methods are
      detailed. The indications for urgent thoracotomy are formulated.

PMID- 9235380
TI  - [Choice of surgical approach in laparoscopic cholecystectomy].
AB  - A definition of a surgical access in laparoscopic interventions is formulated.
      The importance of use of various surgical accesses is stressed. The results of
      treatment of 410 patients with calculous cholecystitis are analysed. 72 of the
      patients have been previously operated on abdominal cavity. The cause of
      technical mistakes and failures are analysed. The original method of ultrasound
      evaluation of abdominal cavity adhesions in patients, who had been operated on
      previously is proposed. The method was used in 45 patients, and in 95% of the
      cases the evaluation was perfectly accurate. Indications for use of a particular
      surgical access, depending on a site of a previous operation, are formulated. The
      method of an open laparoscopy is described. It is indicated in case of previously
      performed low-middle laparotomy and ultrasonic picture of adhesions in the
      umbilical region; in umbilical hernias; in big and multiple choleliths (more than
      30 cubic cm of total volume).

PMID- 9235382
TI  - [Surgical tactics in closed injuries of the liver].
AB  - The results of treatment of 116 patients with closed liver injuries are
      available. 6 types of liver injuries have been determined, depending on location,
      rupture and safety of certain intraliver structures. To evaluate the rate of
      seriousness of a liver injury and decrease the rate of blood loss methods of a
      temporary haemostasis were used; after that the location and depth of the
      ruptures were estimated; safety of the vessels, bile tracts and liver parenchyma
      was evaluated. Nonviable parts of the parenchyma were resected. Various methods
      of haemostasis were used: ligating, laser and plasma coagulation, use of
      synthetic films. The external liver compression with an elastic splint was used
      in case of ineffectiveness of the methods mentioned above. The ligating of the
      hepatic artery should be used in case of the afferent liver vessels injury.

PMID- 9235383
TI  - [Endoscopic peroral pancreatico-cholangioscopy in the diagnosis of diseases of
      bile ducts and the pancreas].
AB  - Till nowadays the diagnosis of biliary and pancreatic ducts disorders remains to
      be rather difficult. Cholangioscopy is the only method, that gives an opportunity
      of visual evaluation of the ducts. The results of 234 retrograde peroral
      pancreatico-cholangioscopies (RPCS) in 149 patients are analysed. 2 systems of
      the "Olympus" endoscopes, including both "mother" and "daughter" apparatus with
      uncontrolled (model PF-24, external diameter 2.4 mm) and controlled distal tip
      (model CHF B 20, external diameter 4.5 mm) were used for the tests. Endoscopic
      papillosphincterotomy has been performed in 87 of the patients, who were later on
      tested with RPCS (147 tests). 38 RPCS have been performed in 29 patients after
      transduodenal papillosphincterotomy. 47 cholangioscopic procedures have been
      undertaken in 31 patients after various types of biliodigestive anastomoses. In 2
      cases RPCS has been performed after the balloon dilatation of the major duodenal
      papilla. The signs of catarrhal cholangitis have been observed in 27% of the
      cases. Purulent cholangitis was present in 13.4% of the patients. Cholangitis was
      detected in 19.5% of the cases in long-term follow up after endoscopic
      papillosphincterotomy; in 88.2% of such cases catarrhal inflammation of duct's
      mucosa was observed. It is stated that after endoscopic surgery cholangitis is
      observed 2.5 times less frequently, than after relevant transduodenal procedure.

PMID- 9235384
TI  - [Erroneous laparotomies in emergency surgery].
AB  - The retrospective analysis of case histories of 28 patients subjected to
      erroneous laparotomies in 1988-1992 has been done. The total number of patients,
      who had urgent abdominal operations for this period of time, was 5115. Atypical
      clinical course of the disease, improper diagnosis and interpretation of the
      disease symptoms, senile age of the patient are major causes of the erroneous
      laparotomies. To avoid erroneous laparotomy laparoscopy and ultrasound
      examination of abdominal cavity should be used widely, other medical specialists
      (urologist, gynaecologist) should be involved in diagnosis, especially in senile
      patients.

PMID- 9235385
TI  - [Contour mammoplasty].
AB  - The article presents the analysis of contour mastoplasty in 350 females. In 333
      cases a bilateral operation has been performed and in 87 cases the operation was
      combined with reduction mastoplasty and other types of corrective operations. In
      99.1% of the patient a good result was achieved. In 4.9% patients various
      postoperative complications were observed. 33.7% patients had a decrease of a
      volume of mammary gland; in 0.85% of patients fibrous contracture was observed
      and 0.57% of patients had insignificant pain. The cosmetic result was stable in
      66.34% of patients within a year after surgery.

PMID- 9235386
TI  - [A rare case of pancreatic tumor causing thrombosis of the splenic vein].

PMID- 9235387
TI  - [Laparoscopic adrenalectomy].

PMID- 9235388
TI  - [Surgical treatment of senile macular degeneration: rotation or
      transplantation?].

PMID- 9235389
TI  - [Employing physician assistants. Legal changes in employment law and effects on
      general practice].

PMID- 9235390
TI  - [Eye involvement in cancer].
AB  - Intraocular metastatic tumors are rare. They are seen in 10% of patients having
      died of a malignant tumor. Frequently metastatic tumors of the eye are not
      observed clinically because the may develop in the terminal stage of the disease.
      The most frequent primary tumor is carcinoma of the breast with 60% of all
      intraocular metastatic tumors followed bronchogenic carcinoma with 19%. While
      breast carcinomas usually metastasize years after excision of the primary tumor,
      bronchogenic carcinomas may metastasize into the eye before the primary tumor
      reveals itself. Corresponding with its blood supply the choroid, particularly the
      posterior pole, is the most frequent manifestation of a metastatic tumor of the
      eye. Here they show the picture of an ill defined, light, slightly prominent,
      round tumor with irregularities of the overlying retinal pigment epithelium. They
      are occasionally misinterpreted as amelanotic malignant melanomas of the choroid,
      nevi, hemangiomas or rhegmatogenous retinal detachment. The prognosis is poor.
      Once a metastatic tumor has manifested itself within the eye the life expectation
      is 7-9 months. Orthovolt radiation with a dose of 30 Gy fractioned over 2-3 weeks
      may be successful. Chemotherapy has not been very satisfactory. We have seen
      metastatic tumors of the choroid that developed during chemotherapy.
      Ophthalmologists are not used to the contact with cancer patients. These patients
      require special care. The relatives should be included in the discussions because
      they suffer as well and may be very helpful in the further maintenance of the
      patient. It is recommended to advise the same doctor to care for the patient
      because this will build up confidence and trust.

PMID- 9235391
TI  - [Endophthalmitis--clinical picture, therapy and prevention].
AB  - BACKGROUND: Infectious endophthalmitis is a dreaded situation in ophthalmology,
      since it often induces a substantial reduction of visual acuity, and in some
      cases the loss of the eye despite modern medication and surgical treatment
      methods. OBJECTIVE OF THE STUDY: Compilation of the most important
      characteristics of postoperative endophthalmitis with acute, delayed and chronic
      course, posttraumatic endophthalmitis and endogenous endophthalmitis. Comprising
      the results of the endophthalmitis vitrectomy study, a review of the
      pharmacotherapy and surgery required is presented. THERAPY: Acute postoperative
      endophthalmitis is treated by a combination of broad-spectrum antibiotics
      (vancomycin and ceftazidime or amikacin), which are administered intravitreally,
      subconjunctivally and topically, if appropriate in combination by systemic
      antibiotics (vancomycin and ceftazidime or amikacin). If vision diminshes to mere
      light perception, performance of pars plana vitrectomy is indicated. Treatment of
      acute postoperative endphthalmitis with delayed occurrence requires that the
      underlying complications (e.g. suture dehiscences) are eliminated, and is carried
      out in accordance with the therapeutic principles for acute postoperative
      endophthalmitis. In chronic postoperative endophthalmitis, which is caused by
      bacteria, antibiotics (aminoglycosides or vancomycin) are administered topically
      and intravitreally. If antibiotic treatment is unsuccessful, a pars plana
      vitrectomy must be performed including posterior capsulotomy, appropriate with
      total removal of the capsular sac including the posterior chamber lens. In
      postoperative mycotic endophthalmitis, antimycotics (amphotericin B) are
      administered intravitreally. If findings are severe, a pars plana vitrectomy must
      also be carried out with excision of capsule, if necessary with removal of the
      posterior chamber lens. Antimycotics are applied topically to support treatment.
      Acute posttraumatic endophthalmitis is treated by intravitreal antibiotic
      administration (vancomycin and ceftazidime or amikacin) in combination with pars
      plana vitrectomy and removal of foreign body. Treatment is supplemented by
      systemic, subconjunctival and topical antibiotic administration. To reduce ocular
      destruction due to inflammation, systemic and intravitreal administration of
      steroids is recommended in all postoperative and posttraumatic endophthalmitis
      conditions. Treatment of endogenous endophthalmitis requires collaboration with
      an internist. Systemic therapy with antibiotics or mycotics is obligatory. In
      addition, broad-spectrum antibiotics (vancomycin or aminiglycosides) or
      antimycotics (amphotericin B) are administered topically and intravitreally in
      these conditions. In severe ocular infections, pars plana vitrectomy is
      indicated. PREVENTION: To reduce the risk of infection, patients with infectious
      eye diseases should be excluded from elective operations. Special attention must
      be paid to risk patients with defects of the immune system. Observation of
      hygienic regulations is obligatory. Prophylactic perioperative administration of
      antibiotics has proved to be effective. Patients suffered from penetrating or
      perforating injuries get systemic antibiotics prophylactically. Qualified follow
      up care of the patient is necessary. CONCLUSIONS: The therapeutic principles for
      treatment of acute postoperative endophthalmitis are determined by the
      endophthalmitis-vitrectomy-study. Further investigations are required with
      respect to corticosteroid use.

PMID- 9235392
TI  - [How successful is the filtering bleb "needling"?].
AB  - BACKGROUND: "Needling" may become necessary when filtering blebs fail due to
      scarring or encapsulation. Our goal was to calculate the medium term success rate
      of the needling procedure. METHODS: The results of 90 needling procedures
      performed on 58 eyes were analyzed, 52 eyes required one single needling (group
      1) after simple trabeculectomy, whereas 19 eyes had to have double needling
      (group 2) and 3 eyes had to be needled 3 times (group 3). These figures do not
      include a 4th group of 16 eyes which had been needled after repeated and
      complicated surgery. Success rates were calculated at t1 = 0 - 1 day, t2 = 1 - 4
      weeks, t3 = 4 - 8 weeks, t4 = 3 - 5 months and t5 = > 6 months after the
      treatment. RESULTS: The mean IOP (n = 90) was 29 +/- 6 mm Hg preoperatively, 15
      +/- 10 mm Hg at t1, 23 +/- 9 mm Hg at t2, 20 +/- 7 mm Hg at t3, 17 +/- 5 at t4
      and 17 +/- 3 at t5. The overall success rates were 80% (t1), 45% (t2), 37% (t3),
      35% (t4) and 31% (t5). The corresponding success rates were 74%, 36%, 32%, 28%
      and 26% for group 1.89%, 52%, 37%, 37% and 31% for group 2.67% at all times for
      group 3 and 100%, 69%, 54%, 54% and 45% for group 4. CONCLUSIONS: In one third of
      all cases the needling is effective for more than 6 months. A complicated
      pressure lowering surgery does not necessarily diminish the effectiveness of a
      needling procedure. Re-needlings are as successful as the first one.

PMID- 9235393
TI  - [Fourier analysis as a mathematical model for evaluating and presenting
      postoperative corneal topography data after non-mechanical perforating
      keratoplasty].
AB  - BACKGROUND: Videokeratography has given the possibility to obtain information in
      curvature from a much larger region of the cornea than that covered by
      keratometry. Fourier analysis as a mathematical model can be used to represent
      real physical attributes of the cornea and to divide corneal topography in its
      basic components: the zero-frequency component as the mean ring power, the one
      cycle component as a representation of decentration and the two-cycle component
      as a representation of regular corneal toricity. The purpose of this study was
      the reconstruction of the corneal refraction after penetrating keratoplasty with
      a small number of characteristic parameters and the evaluation of the time course
      of the fourier coefficients as indices for a regular astigmatic cornea in the
      postkeratoplasty period including suture removal. PATIENTS AND METHODS: Fourty
      patients (group 1: 20 primary dystrophies, group 2: 20 keratoconus) underwent
      nonmechanical trephination (excimer laser MEL60, Aesculap-Meditec, Heroldsberg,
      Germany) in penetrating keratoplasty. All procedures (7.5 mm in dystrophies, 8.0
      mm in keratoconus, 8 orientation teeth, double-running 10-0 nylon suture) were
      performed by one surgeon. At a postoperative gate of 6 weeks, 6 months, before
      partial suture removal and after complete suture removal, corneal topography
      (TMS1, Tomey, Tennenlohe, Germany), keratometry, visual acuity and subjective
      refraction were assessed. Radial approximation with a 5th order polynomial fit of
      the refractive data on 25 non-centric rings of the TMS, within 256 hemimeridians
      was performed to get data at equally spaced concentric rings. Fast Fourier
      transformation of the data sets in the mid periphery (1.4-1.8 mm apical distance)
      was done to get DC-, one-cycle and two-cycle component. Fourier coefficients were
      correlated with keratometric readings, subjective refractive values and visual
      acuity. RESULTS: Spherical equivalent was fairly constant in the postoperative
      interval before suture removal. After suture removal, a corneal flattening of
      about 3 diopters occurred. The one-cycle component before suture removal tended
      to be higher in group 1 compared to group 2 before suture removal. This
      difference was statistically significant (p = 0.01) after suture removal.
      Comparing keratometry, calculated meridians by the Tomey software, two-cycle
      component of the fourier decomposition and subjective refraction, the best
      correlation (p = 0.02) was observed between two-cycle-component and the
      refractive cylinder in amplitude and axis after suture removal. Best corrected
      visual acuity was inversely correlated with the amount of energy of higher
      harmonics compared to the whole energy before (p = 0.04) and after (p = 0.01)
      suture removal. CONCLUSIONS: Fourier transformation renders reconstruction of
      corneal topography data with a marked data reduction and a small error. From
      fourier coefficients conclusions may be drawn concerning potential best-corrected
      visual acuity and amplitude/axis of subjective cylinder, even in corneas with
      severe local irregularities.

PMID- 9235394
TI  - [Intraoperative skiascopy for determining the refractive value of an implantable
      intraocular lens].
AB  - BACKGROUND: Preoperative biometry for calculation of the refractive power of
      intraocular lenses is not sufficiently reliable in certain cases. Most frequently
      inaccuracies tend to occur in highly myopic eyes. Preceding refractive procedures
      can also impair IOL-calculation or even make it impossible. PATIENTS: In a highly
      myopic patient IOL-power calculation was not possible with conventional
      calculation formulas due to a preexisting refractive silicone lens located
      between the cataractuous natural lens and the iris. In another myopic patient
      ultrasound measurement of axial eye length produced variable and unreliable
      results. Therefore retinoscopy was performed intraoperatively in the aphakic eye.
      Refractive power of the IOL was calculated using a new formula. For validation of
      the method retinoscopy was performed intraoperatively in a second group of 11
      patients with unproblematic ultrasound biometry. RESULTS: In 3 eyes IOL power was
      chosen according to intraoperative retinoscopy. A maximal deviation of 1.25 D
      from the aimed refraction resulted. In the second group, the retinoscopic method
      produced partially considerably inaccurate results as compared to the ultrasound
      biometry. Inaccuracies increased with the extent of hyperopia. CONCLUSIONS: In
      cases of difficult or inaccurate preoperative ultrasound biometry IOL power can
      be estimated after intraoperative retinoscopy in the aphacic highly myopic eye.
      IOL power can be calculated instantly using computer programs or tables. This
      method additionally enables the surgeon to control the refractive result of
      intraocular lens implantation prior to wound closure. However this method lacks
      reliability in higher hyperopic eyes, as in these cases small changes in corneal
      vertex distance of the lens used for retinoscopy highly alter the result.

PMID- 9235395
TI  - [Energy metabolism of the human cornea in various culture systems].
AB  - BACKGROUND: There are two well known systems to culture human corneas prior to
      transplantation. First, corneal storage at 4 degrees C especially in Optisol
      medium. Second, organ-culture at physiological temperatures in a modified minimal
      essential medium (MEM). In the cold storage system the number of endothelial
      cells after storage might be overestimated because the damaged cells are not able
      to leave the monolayer. It has been supposed that the lack in energy recruitment
      is the main reason for that, but has not been proven yet. It was the purpose of
      this study to describe the energy status of the human cornea after storage in
      both systems. MATERIALS AND METHODS: 32 human corneas were investigated. They
      were stored for 7 days in Optisol, and for 7 days in MEM plus 1 day in MEM
      supplemented with 5% dextran 500 and 12 days in modified MEM plus 1 day in MEM
      supplemented with 5% dextran 500. The endothelial cell density (ECD) as well as
      the hydration were determined. Glucose, lactate, ATP, ADP and AMP were measured
      to reflect the energy status. RESULTS: Hydration was comparable in all three
      groups. ECD was slightly higher in Optisol stored corneas, although the amount of
      damaged cells was much higher. Optisol stored corneas showed a severe anaerobic
      situation, especially lacate concentrations were increased. In contrast ATP and
      ADP concentrations were twice as high in MEM than in Optisol stored corneas.
      DISCUSSION: The severe anaerobic situation in Optisol stored corneas leads to a
      lack in energy recruitment. This reduces the ability of cell function (mitosis)
      and the function of the monolayer (migration, elimination). Whether these changes
      are reversible after transplantation has to be determined in future.

PMID- 9235396
TI  - [Keratoacanthoma of the eyelid area. Problems and risks in diagnosis and
      therapy].
AB  - BACKGROUND: Keratoacanthoma of the eyelid is a benign skin lesion. Because it
      regresses spontaneously observation without surgical intervention is the
      generally accepted method of management. This concept, which was developed in the
      sixties, is questioned on the basis of personal experience and a review of the
      literature. Recommendations for a rational management of the disease are
      suggested. METHOD: Two patients with clinically diagnosed eyelid keratoacanthomas
      are reported with their complicated disease course. A review of the
      dermatological and ophthalmic literature is presented. CONCLUSIONS: For the
      correct diagnosis a sufficiently large and representative histological specimen
      is mandatory. The difficulty of differentiating between keratoacanthoma and
      squamous cell carcinoma is stressed. Surgery of advanced eyelid lesions is so
      much more destructive that early simple excision is advocated rather than a
      policy of initial observation.

PMID- 9235397
TI  - [Accidental retinectomy in block excision for cystic epithelial ingrowth].
AB  - A 3.5-year-old girl suffered from a penetrating injury of the left eye. One and a
      half years later epithelial ingrowth was detected. Although block-excision was
      performed in the usual manner without technical problems the retina was excised
      accidentally. Histology revealed that the retina had been massively displaced in
      anterior direction prior to surgery because of fibrovascular proliferations.

PMID- 9235398
TI  - [Lens coloboma and lens dislocation in Stickler (Marshall) syndrome].
AB  - BACKGROUND: Both, Stickler and Marshall syndrome are dominantly inherited,
      connective tissue disorders with highly variable individual manifestations.
      Probably, both syndromes represent the same entity with occasional partially
      different clinical manifestations. PATIENT: We are reporting on a female patient
      with typical ocular and systemic manifestations of both syndromes: high myopia,
      glaucoma and goniodysgenesis, submucosal cleft palate, sensorineural hearing
      loss, and "flat" mid-face. Additionally, we observed subluxation of the ocular
      lens in one eye which was previously described in only a few cases. In our case,
      subluxation was combined with nasal coloboma of the lens and congenital cataract.
      This represents the first report of coloboma of the ocular lens as a
      manifestation of Stickler (Marshall) syndrome. In both children of the patient
      manifestations of the syndrome were present (high myopia, cleft palate,
      sensorineural hearing loss). CONCLUSION: Coloboma and subluxation of the lens
      have to be regarded as possible manifestations of the Stickler (Marshall)
      syndrome. The syndrome(s) should be included in the differential diagnosis of
      ectopia lentis-associated systemic diseases.

PMID- 9235399
TI  - [Erosive gastroduodenal ulcers].
AB  - The authors discuss classification and treatment of erosive lesions of the
      stomach and duodenum. For after-care and prevention of recurrences it is
      important to make regular endoscopic check-ups, staged differentiated treatment
      of patients with recurrent erosive gastroduodenal lesions.

PMID- 9235400
TI  - [Non-conventional gastroenterology].

PMID- 9235401
TI  - [Ultrasound diagnosis: current opportunities in diagnosis of gallbladder
      pathology].

PMID- 9235403
TI  - [Ulcer course features in the presence of Helicobacter and Herpes infections].

PMID- 9235402
TI  - [Reparative characteristics of gastric and duodenal mucosa in ulcer].
AB  - Mucosal repair in the stomach and duodenum was assessed clinically and
      morphologically in various ulcer phases in 475 patients with gastroduodenal
      ulcer. It was found that poorly scarring ulcers are characterized by severe
      impairment of regeneration with epithelial proliferation prevailing over its
      differentiation. Participation of immune system, primarily T-cell component, in
      regeneration regulation is shown. Helicobacter pylori is not involved in repair.
      Superoxide dismutase activity in red cells and ulcer edges mucosa is
      prognostically significant indicating the disease phase, completeness of ulcer
      process.

PMID- 9235404
TI  - [Roentgenological assessment of conservative surgery outcomes in duodenal ulcer].
AB  - The results of duodenal ulcer treatment have been analyzed for 240 patients.
      Selective proximal vagotomy (SPV) was performed in 198 patients with
      uncomplicated disease, and SPV with gastroduodenoanastomosis (SPV + GDA) was
      conducted in 42 patients with different ulcer complications. All the patients
      were examined by X-ray before the operation and throughout 10-14 days, 2-3
      months, 1 year and so on each year within 10-15 years. X-ray evidence was
      compared with operative, endoscopy and clinical findings. SPV brought a complete
      recovery in 92.5 while SPV + GDA in 86% of cases. Neither SPV nor SPV+GDA
      contribute to development of cholelithiasis.

PMID- 9235405
TI  - [Essential phospholipids in combined therapy of chronic circulatory
      insufficiency].
AB  - Essential phospholipids (essentiale-forte) was used in combined therapy of 36
      patients with pronounced circulatory insufficiency and hepatic dysfunction. A 4-6
      week course of this treatment 6 weeks after its termination resulted in good
      subjective response, positive changes in hemodynamics, intrahepatic cholestasis,
      synthetic function of the liver and lipid metabolism. The drug was well
      tolerated.

PMID- 9235406
TI  - [Nizatidine++ among the drugs usable in the treatment of acid-dependent gastric
      diseases].

PMID- 9235407
TI  - [About the teacher].

PMID- 9235408
TI  - [Side effects of treatment with non-steroidal antiinflammatory agents and ways of
      their corrections].

PMID- 9235409
TI  - [Cholesterosis of gallbladder: clinical, diagnostic and therapeutic aspects].

PMID- 9235410
TI  - [About Vladimir Kharitonovich Vasilenko].

PMID- 9235411
TI  - [VK Vasilenko: letters and ideas. (To 100 anniversary)].

PMID- 9235412
TI  - [Cardiopulmonary resuscitation in hospitalized patients in conventional units.
      Prospective study of 356 consecutive cases. Commission for Care of
      Cardiorespiratory Arrest].
AB  - BACKGROUND: Information regarding to the system functioning and to the outcome of
      patients in whom cardiopulmonary resuscitation (CPR) was performed during their
      in hospital period in non intensive care units are essentially lacking in Spain.
      The objectives of the present work were: 1) to define clinical and demographic
      characteristics of the patients who develop cardiopulmonary arrest in general
      hospitalization wards; 2) to analyze immediate and late (at discharge) survival
      rates as well as the frequency of severe sequelae in final survivors; 3) to
      identify prognostic factors in relationship to survival, and 4) to detect
      possible internal deficiencies in the organized system of CPR. PATIENTS AND
      METHODS: All patients who develop cardiac and pulmonary arrest through their
      hospitalization in general wards during a three year period, were prospectively
      included. Clinical and demographic data from all the patients as well as data
      related to the internal functioning of the system were recorded. RESULTS: From
      356 included cases, 196 (55%) were initially recovered and 128 (36%) were
      discharged from the hospital. Among the latter group, 12.5% remained with
      severely disabling neurologic damage. Age under 80 years, resuscitation maneuvers
      for less than 20 minutes and respiratory arrest as the ultimate event leading to
      cardiopulmonary arrest were associated with better prognosis. The internal
      deficiencies most commonly recorded in the system were false calling to the
      emergency team, the wrong identification of the location in the hospitalization
      unit and several abnormalities in the content of CPR sets. CONCLUSIONS: With the
      currently available organized system directed towards CPR for patients admitted
      in general hospitalization wards, our rates of success are good and similar to
      those achieved in some intensive care units. Thus, a similar policy may be
      encouraged in large hospitals. Since most of the detected deficiencies in
      internal functioning are easy to rectify, a close monitoring is warranted in
      order to optimize the results.

PMID- 9235413
TI  - [Assessment of quality of life related to health 2 years after coronary surgery].
AB  - BACKGROUND: The determinants of quality of life after coronary artery surgery in
      well defined health care populations are still incompletely understood. The aim
      of the present study was to assess the health related quality of life associated
      with coronary artery bypass surgery as performed in a tertiary public hospital,
      and also to investigate its association with clinical variables. PATIENTS AND
      METHODS: All survivors of a first coronary artery bypass grafting operation
      performed during a calendar year in a single center (100 patients) were included
      for assessment two years after surgery. Assessment included a review of the
      clinical records, a structured clinical interview and the administration of three
      questionnaires of perceived health (Nottingham Health Profile, Duke Activity
      Status Index and SF-36 Health Survey). RESULTS: The mean scores of the
      administered questionnaires corresponded to a moderate overall impairment of
      perceived health, with wide individual variations. Chronic stable postoperative
      angina pectoris (28% of patients), worse clinical functional grade (either due to
      angina or to others causes), comorbidity (51% of patients) and female sex were
      significantly associated with worse scores. CONCLUSIONS: In the study population,
      postoperative angina, impairment of the clinical functional grade (due to angina
      or to other conditions), and female gender were the major determinants of
      impaired health related quality of life after coronary artery bypass surgery. As
      such determinants are associated with anatomoclinical variables in the population
      undergoing coronary bypass surgery and also with perioperative variables,
      appropriate effectively studies appear to be indicated for the assessment of this
      surgical procedure.

PMID- 9235414
TI  - [Analysis of 90 cases of pleural tuberculosis in relation to adenosine deaminase
      levels].
AB  - BACKGROUND: To analyze the adenosine deaminase (ADA) pleural levels and the
      possibility of a typical pattern of tuberculous pleuritis (TP) in relation to
      these values. PATIENTS AND METHODS: We analyzed 90 consecutive cases of TP
      dividend into two groups on the basis of the pleural ADA measurements: group 1
      (less than 43 U/I) and group 2 (equal or higher than 43 U/I). We compared: age,
      sex, tuberculous risk factors, clinic onset and duration, PPD, chest
      roentgenogram, biochemical (LDH, glucose and proteins) and cytological
      examination of the pleural fluid, microbiologic studies on sputum, pleural fluid
      and biopsies, histologic findings of the biopsies, evolution and sequelae after
      the treatment. RESULTS: 36 patients in the group 1 (40%) and 54 in the group 2
      (60%) (p = 0.01). All the parameters were similar in both groups excluding LDH
      pleural levels, that were higher in group 2. In 20 cases of the group 1, we
      obtained a second analysis of pleural ADA and we observed in 11 cases (55%) an
      ADA value above 43 U/I. CONCLUSIONS: We confirmed that ADA pleural level is
      increased in the majority of our patients with a low initial sensibility of 60%,
      that can increase with a second determination (72%). ADA activity below 43 U/I
      cannot exclude the tuberculous aetiology of an effusion and can persist negative
      in other analyses. The results suggest a response of different chronology without
      any relation to initial ADA pleural level.

PMID- 9235415
TI  - [Cardiopulmonary resuscitation admitted to units of conventional
      hospitalization].

PMID- 9235416
TI  - [Health-related quality of life: a new parameter to keep in mind].

PMID- 9235417
TI  - [Guideline for the evaluation of health science research projects. Group of
      Evaluation of the Activities of the Fund for Health Research from 1988 to 1995].

PMID- 9235418
TI  - [Adhesion molecules in the interactions of leukocytes, endothelium, and
      extracellular matrix (I). Structure, distribution, and biological function].

PMID- 9235419
TI  - [Comments on the clinicopathological conference "Fever, dyspnea, and palpitations
      in a 53-year-old woman"].

PMID- 9235420
TI  - [Splenic lymphoma of the marginal zone].

PMID- 9235421
TI  - [Oral leukoplakia].

PMID- 9235422
TI  - [Kluyvera ascorbata bacteremia].

PMID- 9235423
TI  - [Delayed thrombolytic administration in myocardial infarction;].
AB  - BACKGROUND: The aim of the study is to know whether the patients with acute
      myocardial infarction (AMI) who consulted an extrahospitalary physician before
      the hospital arrival delayed their admission to the critical care unit (CCU), and
      whether their probability to receive early thrombolytic therapy was smaller than
      that of the patients who cam directly to hospital. PATIENTS AND METHODS: A
      descriptive study in patients with AMI was performed during 1995. The following
      variables were studied: age, sex, town of residence, previous AMI, consultation
      to an extrahospitalary physician, delay time in the admission to the CCU, and
      whether thrombolytic treatment was performed. Comparison of proportions, Student
      Fisher t-test, or Mann-Whitney U-test were used, according to the case. A
      multiple logistic regression was used to study the independent effect of the
      previous consult to an extrahospitalary physician on the chance for early
      thrombolytic treatment. RESULTS: A hundred and eighteen patients (79.7% males)
      were studied. The mean age was 63 years-old. Nine point five per cent of the
      patients had suffered a previous AMI and 54.2% received thrombolytic treatment.
      Delay to hospital arrival was the main exclusion reason to receive this
      treatment. The mean age of patients who consulted an extrahospitalary physician
      (n = 69) was 5 years older, their hospital arrival were 100 min later (difference
      of medians) (p < 0.001), were admitted to the CCU 124 min later (p < 0.02) and
      ran a higher risk to arrive to CCU after 3 hours from the onset of symptoms (odds
      ratio [OR]: 3.3; confidence interval [IC] 95%: 1.2 to 9.2) than those who cam
      directly to hospital. CONCLUSIONS: The patients with AMI who consult an
      extrahospitalary physician delay their admission to the CCU and have a less
      chance to receive early thrombolytic therapy in the first 3 hours of evolution.

PMID- 9235424
TI  - [The white coat effect in primary care. Analysis of patients with newly diagnosed
      arterial hypertension].
AB  - BACKGROUND: In a non-selected group of hypertensive patients with a new diagnosis
      at primary care, blood pressures obtained in the office (oBP) are compared to
      ambulatory ones (aBP). White coat hypertension (WCH) and white coat phenomenon
      (WCP) are estimated to evaluate a white coat effect on such population. PATIENTS
      AND METHODS: An ambulatory blood pressure monitoring (ABPM) was performed to 91
      hypertensive patients (55 females) from 21 to 70 years-old, with consecutive
      diagnosis in 4 office rooms in an health center (oBP mean > or = 140 mmHg for
      systolic blood pressure and/or 90 mmHg for diastolic blood pressure during three
      measures at least). WCH was defined by systolic aBP < or = 135 mmHg and diastolic
      < or = 85 mmHg, simultaneously, and WCP by oBP-aBP differences > or = 20 and/or
      10 mmHg (for respective systolic and diastolic blood pressure). RESULTS: oBP
      systematically exceeded aBP with wide variations for each subject (difference
      mean +/- SD: 15 +/- 13/7 +/- 9 mmHg for systolic/diastolic), sex (female: 19 +/-
      12/11 +/- 9, male 8 +/- 11/2 +/- 9) and depending on the observer who made the
      measure. WCH was detected in 27 patients (22 females), and WCP in 47 (37
      females), so 30% (confidence interval [CI]: 21-40%) and 52% (CI: 41-62%)
      respective prevalences are supposed. CONCLUSIONS: Within primary care, white coat
      effect causes a substantial hypertension sobrediagnosis as quantitative as
      qualitatively. Confirming measures made by nurses and additionally, ABPM for
      women, seem to lessen this effect.

PMID- 9235425
TI  - [Description and study of the etiology of a community outbreak of atypical
      pneumonia in L'Espluga de Francoli, Tarragona].
AB  - BACKGROUND: A community outbreak of atypical pneumonia occurred in summer 1994 in
      L'Espluga de Francoli, Tarragona, Spain, affecting 20 people. PATIENTS AND
      METHODS: The clinical and epidemiologic description of the outbreak are
      performed, as well as the sanitary actions leading to the discovery of the
      original focus (an hotel refrigerating tower). Through case-control studies
      (among the 17 in-home contagions according to their nearness) and using the
      causality criteria of Evans and Bradford-Hill. RESULTS: Although the
      symptomatical description brings forth new symptoms such as hyperglycemia or
      livedo reticularis, the comparative clinical-therapeutical study bears no
      significant differences with other series, and the radiological data as well as
      the response to the treatment are wholly overlapping, with results less
      coincident in those coming from the lab, very specially due to the small
      sensibility the indirect immuno-fluorescence showed. CONCLUSIONS: The
      epidemiologic study demonstrates the etiology of the outbreak (Legionella), their
      source in the refrigerating tower, in so much sterilization coincided with the
      end of the epidemy.

PMID- 9235426
TI  - [The physician as a poor prognosis factor].

PMID- 9235427
TI  - [The white coat: does it still scare people?].

PMID- 9235428
TI  - [A model for the analysis of academic performance in medicine].

PMID- 9235429
TI  - [Adhesion molecules in the interactions of leukocytes, endothelium, and
      extracellular matrix (II). Relevance in human clinical medicine and potential
      therapeutic applications].

PMID- 9235430
TI  - [Sample size in research papers].

PMID- 9235431
TI  - [Is the habit of smoking crack becoming widespread in Spain among heroin users?].

PMID- 9235432
TI  - [Pre-hospital fibrinolysis in Spain].

PMID- 9235433
TI  - [The chronic patient and the internist: a necessary encounter].

PMID- 9235434
TI  - [Thiabendazole hypersensitivity].

PMID- 9235435
TI  - [Lars-Otto Dandenell, rehabilitation physician in Tranas: spas and thermal baths
      strengthen both body and soul].

PMID- 9235436
TI  - [More pathologists are needed in Sweden! Retirements may cause a real crisis].

PMID- 9235437
TI  - [Form-filling is a curse. The paper work takes too much time from the patients].

PMID- 9235438
TI  - [Alarmingly inadequate clinical evaluation and marketing of intrauterine
      devices].

PMID- 9235439
TI  - [A visual phenomenon as migraine manifestation].

PMID- 9235440
TI  - [General practitioners as usually incompetent].

PMID- 9235441
TI  - [Impossible prescription forms result in unreasonable workload].

PMID- 9235442
TI  - [Laboratory diagnosis of acute pancreatitis. Amylase analysis is still the
      leading one, but a "urinary strip" is on its way to be marketed].

PMID- 9235443
TI  - [Acute myeloid leukemia. Achievements and challenges in the treatment of adults].

PMID- 9235444
TI  - [Drug analysis during epilepsy treatment is valuable].
AB  - Therapeutic drug monitoring (TDM) of antiepileptic agents has been an invaluable
      aid in efforts to individualise epilepsy treatment since the 1970s. In few
      series, however, have attempts been made to assess the impact of TDM on the
      outcome of epilepsy therapy. The value of TDM has often been questioned in recent
      years, mainly due to the poor results obtained with its inappropriate use.
      Guidelines for the use of TDM of antiepileptic agents are therefore presented and
      discussed in this review. The usefulness of TDM varies according to the drug
      monitored, depending on its pharmacokinetic properties and on whether correlation
      is known to exist between the serum concentration of the drug and its effect. TDM
      is a prerequisite for the safe use of phenytoin, for example, but is of very
      limited value in connection with vigabatrin treatment. Of other novel
      antiepileptics, TDM would probably be useful in connection with lamotrigine
      treatment, and perhaps in connection with topiramate or gabapentin treatment.
      However, the rational use of TDM is hampered by the lack of properly designed
      concentration-effect studies of the new antiepileptic drugs.

PMID- 9235445
TI  - [New glucocorticoids are more selective. Current knowledge can eliminate serious
      adverse effects].
AB  - Glucocorticoids have been used as anti-inflammatory, anti-allergic and
      immunosuppressive agents since the beginning of the 1940s, and during recent
      years the mechanisms by which they exert their anti-inflammatory effects have
      begun to be better understood. Inhibition of inflammatory response is primarily
      mediated via the glucocorticoid receptor and the two transcription factors, AP-1
      and NF kappa B, which are of crucial importance for the expression of pro
      inflammatory cytokines and other genes involved in the inflammatory process.
      Unfortunately, long-term treatment with glucocorticoids is associated with a
      series of adverse effects such as hypertension, bone fragility, diabetes,
      dermatrophy and personality changes. However, owing to advances in biotechnology
      and recent clarification of the molecular mechanisms involved, it is now becoming
      possible to develop new glucocorticoids with a more selective anti-inflammatory
      effect without serious side-effects.

PMID- 9235446
TI  - [Pinch grafting in slow-healing leg ulcer. An old method becomes popular again].

PMID- 9235447
TI  - [A case report. An unusually enlarged heart turns out to be caused not by heart
      failure, but a cyst].

PMID- 9235448
TI  - [Restenosis--elusive shadow of vascular biology. New discoveries set hopes about
      future therapy].

PMID- 9235449
TI  - Adults die younger in the former Soviet republics.

PMID- 9235450
TI  - Anaesthetics: cracking a nut without a sledgehammer.

PMID- 9235451
TI  - Sick-building syndrome.

PMID- 9235452
TI  - European health research.

PMID- 9235453
TI  - Authorship: is there an identity crisis?

PMID- 9235454
TI  - Relational databases for medical audit.

PMID- 9235455
TI  - [Home respiratory care and respirator weaning. Annual meeting of the work group
      for home and longterm respiratory care. Marburg, 11-13 April 1996].

PMID- 9235456
TI  - [Pathophysiology and clinical aspects of global respiratory insufficiency].
AB  - Patients in hypercapnic respiratory failure have got a poor prognosis. The
      recognition of pathophysiological mechanisms is required in order to choose
      adequate therapy. During the past years it has been shown that pathological
      respiratory events during sleep occur early in the disease process and that blood
      gas changes are usually most pronounced during sleep. Minute ventilation and
      functional residual capacity (FRC) decrease during sleep even in normal subjects
      and upper airway resistance increases markedly. PO2 slightly decreases and paCO2
      increases. In most patients with hypercapnic respiratory failure episodes of
      marked hypoxemia and hypercapnia occur, mainly during REM sleep. Suggested
      pathomechanisms are worsening ventilation-/perfusion mismatching, impaired
      respiratory muscle function and a reduction in ventilatory drive, the latter two
      being of major importance. The relation between load and capacity is shifted
      towards an increased load and ventilatory drive is decreased at the same time.
      Therapeutic strategies that reduce the load of the respiratory pump, increase
      minute ventilation and prevent sleep related hypoventilation, thus noninvasive
      ventilation should be used. Symptoms of hypercapnic respiratory failure are often
      unspecific. Dyspnea, headache and awakening from sleep with dyspnea are often
      reported. Signs of right heart failure will be present in advanced disease
      stages. Early diagnosis and treatment provided, noninvasive ventilation achieves
      excellent improvement of both quality of life and life expectancy, especially if
      the primary disease progress is not rapidly progressive.

PMID- 9235457
TI  - [Nasal mask ventilation in the postoperative phase].
AB  - Noninvasive respiration modes have recently gained growing importance. Just with
      patients which are respiratory insufficient due to neuromuscular diseases or
      severe kyphoscoliosis, encouraging experiences have been made. We report about
      nasal ventilation in patients with restrictive lung disorders undergoing severe
      spine surgery, in part as thoracotomy. Here one usually can expect postoperative
      pulmonary complications which often lead to long-time intubation and artificial
      ventilation. In a majority of cases postoperative nasal ventilation allows early
      extubation within 24 hours postoperatively. From 27 patients 23 could be
      extubated at the first day postoperatively, 3 more were extubated definitively
      until day 3.

PMID- 9235459
TI  - [Anemia increases work of breathing in patients with lung disease].
AB  - BACKGROUND: Pulmonary diseases with marked disorders in gas exchange or chronic
      overload of the respiratory pump needs increased ventilatory requirements.
      Additionally in these patients anemic may aggravate the ventilatory load. We
      thereby evaluated whether in these patients treatment of anemia (red blood cell
      transfusion: RBCT) leads to an improvement of the ventilatory load in comparison
      to the anemic patients without pulmonary disease. PATIENTS AND METHODS: We
      examined 21 patients with an anemia (Hb < 11 g%, 12 men). Fifteen patients had a
      pulmonary disease (group A), 6 patients suffered from anemia without pulmonary
      disease (group B). Subsequently within 8 hours the patients got 2 to 3 RBCT. We
      studied the patients on the day of admission and 24 to 36 hours after
      transfusion. The patients kept bed rest for spontaneous breathing 1 hour prior to
      the actual examination without supplemental oxygen. Hemoglobin, hematocrit,
      respiratory rate, respiratory minute volume and arterial blood gases were
      measured. On the following day we repeated the same procedures. RESULTS AND
      CONCLUSIONS: Anemia in patients with an increased ventilatory requirement causes
      an additional increase of work of breathing. In these patients-in contrast to
      patients without compromised lungs-2.2 red blood cell transfusions lead to an
      impressive reduction of VE (about 20%) and correspondingly also to a reduction of
      WOB.

PMID- 9235458
TI  - [Cardiorespiratory polygraphy in differential diagnosis of respiratory
      insufficiency in patients after coronary artery bypass operation].
AB  - BACKGROUND: In intensive care medicine it is well established how to diagnose
      respiratory insufficiency caused by cardiopulmonary diseases. However, there is
      no consensus how to diagnose respiratory insufficiency which may be caused by
      extrapulmonary disturbances of the respiratory apparatus. PATIENTS AND METHODS:
      In 5 patients we performed postoperatively a cardio-respiratory polygraphy for 12
      to 13 hours using Polymesam. This unit allows to record airflow, respiratory
      movements of the chest and abdomen, arterial oxygen saturation, heart rate, body
      position and EKG. RESULTS: The present case-series-study demonstrates that
      patients after arterio-coronary bypass surgery may present respiratory
      insufficiency caused by extrapulmonary disturbances of the respiratory apparatus
      (central and obstructive apnea and hyoponea). The respiratory insufficiency
      occurs during nighttime even when supplemental oxygen (2 to 3 1/min) is
      delivered. CONCLUSION: We conclude that the cardiopulmonary polygraphy for
      assessing respiratory insufficiency in patients after coronary bypass surgery is
      important, in order to avoid severe arterial hypoxemia which may produce
      cardiovascular instability in these patients.

PMID- 9235460
TI  - [Endoscopic placement of an intratracheal oxygen catheter--description of a new
      method].
AB  - BACKGROUND: In patients with disturbed gas-exchange intratracheal oxygen
      insufflation improves oxygenation and reduces the minute ventilation. Until now
      the intratracheal oxygen insufflation was performed using a tracheostomy or a
      percutaneous transtracheal technique. We studied the acceptance and efficacy of
      the intratracheal oxygen insufflation using a bronchoscopic technique of
      intratracheal catheter placement. PATIENTS AND METHODS: Five COPD-patients (4
      men, 55.2 +/- 10.3 years; FEV1: 0.9 +/- 0.31 = 30.3 +/- 5.5% debit, pO2: 56.2 +/-
      10.3 mmHg, pCO2 +/- 43.1 +/- 4.8 mmHg). Procedure of catheter placement: Through
      a nasally passed bronchoscope a guide wire was inserted into the proximal part of
      one bronchus. When positioned at the point 2 to 3 cm proximal to the carina, the
      bronchoscope was marked with plaster at the nasal ostium in order to measure this
      distance. After removing the endoscope, the oxygen catheter was inserted proximal
      to the carina using the guide wire. Before and during the intratracheal oxygen
      insufflation (flow: 3 l/min) minute ventilation, tidal volume, breathing
      frequence, blood gases and the subjective scores (using a visual analogue scale)
      were measured. RESULTS: Apart from one patient with a tolerable spontaneous
      declining urge to cough irritation the catheter was tolerated well during the
      study. Whereas pCO2 remained stable during the ITO2 (before ITO2: 43.1 +/- 4.8
      mmHg; after 1 hour ITO2: 44.3 +/- 4.8 mmHg), the oxygenation improved (pO2: 56.2
      +/- 10.3; 81.4 +/- 19.6 mmHg) and the minute ventilation decreased (7.5 +/- 1.8;
      5.4 +/- 1.3 l/min) by approximately 28%. CONCLUSION: The bronchoscopic
      application of the intratracheal oxygen catheter was characterized by high
      acceptance, low invasiveness and immediate function. Furthermore, the minute
      ventilation and work of breathing respectively decreased to a relevant degree.

PMID- 9235461
TI  - [Noninvasive ventilation in acute respiratory insufficiency].
AB  - BACKGROUND AND AIM: Noninvasive positive pressure ventilation (NPPV) via face
      mask offers in comparison to endotracheal intubation in treating patients with
      acute respiratory failure (ARF) advantages like allowing swallowing and coughing.
      We report our experiences and try to verify the indications and the efficacy of
      NPPV. PATIENTS AND METHODS: In the period of January 1991 until August 1996 109
      patients (30 female, 79 male, mean age 61 +/- 12 years) received mechanical
      ventilation with NPPV representing 25% of all MVs in this term. As baseline
      capillary blood gases (CBG) were found: pH: 7.30 +/- 0, 10; pCO2: 64 +/- 19; pO2:
      60 +/- 19 (all patients received supplemental oxygen). Success of NPPV was
      determined by an improvement of the baseline CBG. RESULTS: NPPV was successful in
      77 (71%) patients. Considering the kind of respiratory insufficiency the patient
      population was divided into 4 groups 1. acute hypoxemic respiratory failure, 2.
      acute hypercapnic ventilatory failure, 3. acute decompensation of chronic
      respiratory insufficiency (CRI) and 4. combined failure. Considering these
      subgroups we obtained the best results in the group of patients with hypercapnic
      disturbances. In patients with hypoxemic RF we observed a success of NPPV if the
      improvement of CBG occurred in the early stage (< or = 12 hours) of NPPV.
      CONCLUSION: Our data indicate that application of NPPV is an effective and safe
      alternative to endotracheal intubation in many patients with hypercapnic
      ventilatory failure. NPPV is also successful in patients with hypoxemic RF with a
      milder course.

PMID- 9235463
TI  - [Pro: noninvasive positive pressure ventilation in respiratory insufficiency].
AB  - Patients who develop acute exacerbation of a chronic pulmonary disease (COPD),
      neuromuscular dysfunction and/or disorders of the ventilator control often
      require assistance of ventilation. transtracheal intubation presents risks of
      nosocomial pneumonia and injuries. There is general agreement that in patients
      with chronic alveolar hypoventilation noninvasive positive pressure ventilatory
      assistance improves ventilation, quality of life, and prolongs survival.
      Recently, some studies also demonstrate that noninvasive positive pressure
      ventilation may offer an alternative to intubation in some patients with COPD and
      lung edema. Noninvasive ventilatory assistance has benefits compared to
      ventilatory assistance via intubation if certain safeguards were used. These
      safeguards include extensive institutional experiences for noninvasive positive
      pressure ventilations, adequate physicians and respiratory care technicians to
      provide bedside skilled care and preparedness of emergent intubation, and the
      patient's mental alertness to tolerate noninvasive ventilatory techniques. The
      most pronounced benefits of noninvasive positive pressure ventilation was absence
      of side effects, shortening of time spent in ICU. The present clinical data
      support the hypothesis that noninvasive positive pressure ventilation may be an
      alternative for intubation in patient with acute respiratory failure and suggest
      further clinical investigative support.

PMID- 9235462
TI  - [Noninvasive ventilation in the acute care hospital--a cost factor?].
AB  - BACKGROUND: Noninvasive ventilation as well established in treatment of chronic
      respiratory failure. Many announcements and our own experience give evidence that
      this method of treatment is useful for patients with acute respiratory failure
      too. Also the actual situation of our health system requires increasing attention
      to financial points of view. PATIENTS AND METHOD: We analyzed a number of 185
      patients who needed mechanical ventilation in our intensive care unit in 1995. 80
      of these 185 needed mechanical ventilation due to pulmonary and cardiopulmonary
      diseases (e. g. cardiac failure, exacerbation of chronic obstructive lung
      disease, pneumonia and status asthmaticus). 61 received invasive, 19 noninvasive
      ventilation. RESULTS: Nineteen of 61 patients with invasive and 1 of 19 with
      noninvasive ventilation died. The mean duration of ventilation was 8.9 (1-50)
      days in the invasive ventilated group and 2.9 (1-8) days in the noninvasive
      ventilated group. A cost reduction of nearly 10000 Marks per patient can be
      calculated, using noninvasive ventilation due to the shorter duration of
      treatment. CONCLUSION: So noninvasive ventilation is a cost reducing and gentle
      alternative compared to conventional invasive mechanical ventilation for many
      patients with acute respiratory failure. It is also practicable in regional
      hospitals. Further investigation is needed to specify those groups of patients
      who receive the most benefit from noninvasive ventilation.

PMID- 9235464
TI  - [Contra: noninvasive ventilation in acute respiratory insufficiency].
AB  - Mechanical ventilation via a tracheal tube is an invasive measure whose
      complications may prevent recovery from respiratory failure. Today, noninvasive
      positive pressure ventilation via mouthpiece or mask is an economically and
      medically successful alternative for the treatment of chronic respiratory failure
      and acute exacerbation of COPD, respectively. Within certain limits, noninvasive
      ventilation may take over inspiratory work of breathing as well as elevate mean
      airway pressure and inspiratory oxygen concentration. This does not at all
      question the absolute indications to maintain a patent airway by tracheal
      intubation. Clinical applications of noninvasive ventilation within these limits
      are acute exacerbation of COPD, congestive heart failure with pulmonary edema or
      atelectasis. Respiratory muscle fatigue, cardiogenic and septic shock, severe
      pneumonia and ARDS are still absolute indications for invasive ventilation. Table
      1 specifies 12 disadvantages and endpoints of noninvasive mechanical ventilation.

PMID- 9235465
TI  - [Report of experiences from the viewpoint of patients. Weaning--an inescapable
      battle with respiratory insufficiency?].

PMID- 9235466
TI  - [Living and experiencing with compensated respiratory insufficiency. From
      ventilator dependence under water].

PMID- 9235467
TI  - [Ventilation--and what then? Report of experiences from the viewpoint of the
      German Society of Muscular Diseases e.V. DGM].
AB  - Without doubt respiratory improves life conditions and quality of life of people
      suffering from neuromuscular disease. Concerning medical-technical possibilities
      there are only few problems. The respiratory machines, developed during the last
      years, allow an outpatient treatment with special masks as well as with help of
      tracheotomy. Yet the medical concept has only small effects if there is something
      wrong with the psychosocial and psychological conditions. Considering the fact
      that respiratory prolongs patients life but does not cure, there is a serious
      problem for patients, their families, the nursing staff and-more and more
      doctors. For the patients and their families as well as the nursing staff it is
      necessary to get qualified at time for the outpatient situation already before
      dismission from hospital. Afterwards they need additional advice and support for
      solving the daily-life-problems and for saving care-quality in an extensive
      sense.

PMID- 9235468
TI  - [New therapy aspects of chronic respiratory insufficiency].
AB  - The therapy of chronic respiratory insufficiency has been extended in the last
      years. Additional to long-term oxygen therapy nasal CPAP-therapy and home
      mechanical ventilation have been introduced. The different kinds of therapy are
      the results of different pathophysiologic alterations in the different forms of
      chronic respiratory insufficiency. In parenchym diseases of the lung with
      hypoxemic respiratory insufficiency the hypoxemia is treated by increasing the
      inspiratory oxygen concentration. Ventilatory pump failures can be divided in 3
      large groups: respiratory muscle fatigue, central alveolar hypoventilation and
      recidive pharyngeal obstruction during sleep. The therapeutic principles are
      relieving of the respiratory muscles by intermittent assisted or better
      controlled mechanical ventilation in muscle fatigue, securing the alveolar
      ventilation by controlled mechanical ventilation in central alveolar
      hypoventilation and pneumatic splinting of the pharyns by nasal CPAP in
      obstructive sleep apnoe.

PMID- 9235469
TI  - [Reproducibility of inspiratory mouth occlusion pressure with a mobile computer
      assisted measuring system].
AB  - BACKGROUND: The measurement of mouth occlusion pressure is an easy method to
      assess respiratory drive and muscle function. In addition to a variety of
      stationary systems, recently a mobile computer assisted system became available.
      In this study the repeatability of inspiratory mouth occlusion pressures with
      such a mobile system was examined. METHOD: Maximal inspiratory mouth occlusion
      pressure (PImax), mouth occlusion pressure 100 ms after onset of normal
      inspiration (P0,1), and PImax after 100 ms (P0,1max) were investigated 4 times in
      12 healthy subjects. Measurements were performed with a mobile system (resPImax).
      Criteria of repeatability were analysis of variance, intraindividual standard
      deviation, variation coefficient and intraclass correlation coefficient. RESULTS:
      Of all analyzed parameters PImax was most reproducible with a 5.3% share of
      variance due to measurement methods of the total variance. P0,1 was least
      reproducible. There was no statistically significant difference between the
      results of each day. The variance due to measurement methods varied between 5.3%
      and 30%. CONCLUSION: The repeatability of mouth occlusion pressures with this
      mobile device was good and partly superior to stationary systems. The concept of
      a mobile measuring unit simplifies getting results of bed-bound and mechanically
      ventilated patients.

PMID- 9235470
TI  - [Epidemiology and diagnosis of intermittent self-ventilation].
AB  - The purpose of the lung is intrapulmonary gas exchange. The circulatory system
      delivers the respiratory gases to the tissue. The ventilatory pump however is
      responsible for the circulation of air between the lungs and the ambient
      atmosphere. Due to better diffusing capabilities, hypercapnia always is a result
      of pump failure and little dependent on the lung. Ventilatory failure, either
      compensated with an increased demand on the muscles or decompensated with an
      additional increase in pCO2, should be separated from lung failure where
      primarily oxygen exchange is involved. Decompensated hypercapnic ventilatory
      failure is then the indication for intermittent mechanical ventilation. The pCO2,
      either arterial or transcutaneously registered together with the noninvasive
      evaluation of the mouth occlusion pressures during tidal breathing and during a
      maximal inspiratory effort, define well the severity of ventilatory failure. In
      acute on chronic ventilatory failure, noninvasive mechanical ventilation in three
      randomised and controlled studies resulted in a better survival compared to
      intubation. To fulfil certain weaning criteria is no longer required in difficult
      to wean patients, as a transfer from invasive to noninvasive mechanical
      ventilation can be performed if only cooperativity is preserved together with a
      minimal capacity of spontaneous breathing. Weaning will thereafter occur by
      progressive relief from intermittent noninvasive ventilation. 2300 difficult to
      wean patients in Germany should profit from this approach. Chronic ventilatory
      failure as a result of neuromuscular disease or scoliosis of the thoracic spine
      are the classical indications. COPD and myasthenia gravis are under discussion as
      indications for intermittent mechanical ventilation with an increasing tendency
      to ventilate. Epidemiological data however can only be roughly estimated due to
      the heterogeneity of indication and selection of the patients.

PMID- 9235471
TI  - [6 minute walking test as stress test for patients treated by intermittent self
      ventilation].
AB  - BACKGROUND: Until now there are no data about the exercise capacity of patients
      with chronic ventilatory pump failure before and during IPPV. PATIENTS AND
      METHODS: 55 patients with chronic ventilatory failure-20 patients before IPPV, 35
      patients during mechanical ventilation with a mean of 16.5 months-were studied by
      the six-minute walking test. Eight patients were sampled in a follow-up study
      before and during IPPV with a mean of 2 months. RESULTS: The median walking
      distance was reduced to 273 in. The exercise capacity of the follow-up patients
      was not improved. The arterial pO2 during exercise fell markedly, arterial pCO2
      increased only moderate. CONCLUSION: The exercise capacity of patients with
      chronic ventilatory failure is markedly reduced. Because of the significant
      oxygen desaturation on exercise we may frequently indicate ambulatory oxygen
      therapy.

PMID- 9235472
TI  - [Increased physical activity due to intermittent self-ventilation in chronic
      respiratory insufficiency].
AB  - BACKGROUND: Nocturnal mechanical ventilation (NMV) can reduce symptoms of
      hypoventilation and improve gas exchange in patients with chronic respiratory
      failure but there is no data concerning the impact of nocturnal mechanical
      ventilation on daily activity. We prospectively measured daily activity as judged
      by total steps per day. PATIENTS AND METHODS: Thirty stable patients (17 men,
      mean age 55.2 years, pCO2: 62.3 +/- 9.0 mmHg) with chronic respiratory failure.
      DIAGNOSIS: Kyphoscoliosis (n = 11), COLD (n = 7), neuromuscular diseases (n = 6),
      post-tbc sequelae (n = 6). Applying a pedometer over a 7 day period before and 3
      months after initiating nocturnal mechanical ventilation the steps per day were
      counted. We also obtained arterial blood gases and applied the St. George's
      Respiratory Questionnaire (scoring range from 0 = complete health to 100 = worst
      possible). RESULTS AND CONCLUSIONS: The daily activity in patients with
      hypercapnic respiratory failure as judged by the total amount of steps per day
      increased by 120% after 3 months of nocturnal mechanical ventilation (from 1606.9
      +/- 1341.3 to 3535 +/- 1813.8 steps per day, p < 0.0001). This was associated
      with a significant improvement in daytime blood gases and quality of life (QoL)
      as judged by questionnaire (total score: from 61.3 +/- 14.9 to 48.3 +/- 18.7, p =
      0.0006). However no correlation between steps per day and QoL was found.

PMID- 9235473
TI  - [The etiology of chronic hypercapnia].
AB  - BACKGROUND: The ventilatory and the pressure response to CO2 in patients with
      advanced thoracic disorders are critically dependent on the mechanics of the lung
      and the respiratory muscles. Changes in drive, therefore, can not be directly
      assessed with that method. However during changes as a result of intermittent
      mechanical ventilation, changes in drive can be assessed, if lung and muscle
      mechanics remain unaffected. In addition, to study changes in ventilatory drive
      independently in patients successfully treated by intermittent mechanical
      ventilation, we determined the recruitment threshold, pCO2RT, of the unloaded
      ventilatory pump to CO2. PATIENTS: 16 patients with various disorders (4 COPD, 4
      COPD and sleep apnoea, 7 scoliosis, 1 fibrothorax) were studied, 14 during nasal
      IPPV and 2 during mechanical ventilation via tracheostomy. RESULTS: After they
      had been successfully adapted to the ventilator, they were entered into the
      study. The apnoea threshold in all cases had already been reached during the
      adaptation period. pCO2AT was determined 32 +/- 5 mm Hg. While the patients were
      passively ventilated, the inspiratory CO2 was increased every 5 minutes,
      resulting in a stepwise increase in arterial pCO2 by 3 mm Hg. The recruitment
      threshold pCO2RT was then defined as the lowest pCO2, which resulted in a
      deformation of the inspiratory pressure curve by the patients own inspiratory
      efforts. pCO2RT was reproducible within trials and in different trials with a
      standard error of 1.2 mm Hg. It was found 6 +/- 4 mm Hg above the pCO2 during
      spontaneous breathing (p < 0.01) in all patients. pCO2RT decreased from 58 +/- 10
      to 47 +/- 4 mm Hg during intermittent IPPV and so did the threshold during CO2
      rebreathing, while spontaneous pCO2 decreased from 53 +/- 12 to 42 +/- 5 mm Hg.
      The slope, reflecting drive was decreased to 0.28 compared to normals but
      remained unchanged 0.32 (n. s.) during the study. Lung function did not change. A
      highly significant increase in the indices of maximal inspiratory force was
      observed (p < 0.002) and as a result a decrease in the inspiratory demand (p <
      0.008). CONCLUSION: Intermittent IPPV does efficiently suppress phasic
      respiratory drive via thoracic afferent inhibition and therefore effectively
      unloads the ventilatory pump. The CO2 threshold is increased in patients with
      hypercapnic ventilatory failure, probably to minimise the load to the ventilatory
      muscles. With the increase in inspiratory capacity the pCO2 threshold can be
      restored to normal by intermittent noninvasive or invasive IPPV.

PMID- 9235474
TI  - [Effect of noninvasive ventilation on pulmonary artery pressure in patients with
      severe kyphoscoliosis].
AB  - BACKGROUND: Many studies have shown, that non invasive ventilation via nasal
      access can normalize alveolar ventilation for individuals due to kyphoscoliotic
      deformity. The purpose of this study was to evaluate the effect of nasal IPPV on
      the pulmonary artery pressures (Pam) and the sleep efficiency of kyphoscoliotic
      individuals. PATIENTS AND METHODS: Five patients were studied (4 men, 1 woman;
      age 50.5 +/- 6.9 years): all patients showed hypoxemia and hypercapnia before
      therapy. We followed the patients about 6 months under NIPPV. We measured PImax,
      PaO2, PaCO2, Pam before and after 6 months with NIPPV. RESULTS: PImax increased
      from 4.9 +/- 2.3 kPa to 6.5 +/- 1.3 kPa, PaO2 increased from 46.2 +/- 12.2 mmHg
      to 56.7 +/- 8.5 mmHg. PaCO2 decreased from 53.0 +/- 3.2 to 45.3 +/- 3.2. Pam
      decreased from 41.0 +/- 15.1 to 23.2 +/- 10.7 in 6 months of NIPPV. Total sleep
      time increased from 222 +/- 52 min to 326 +/- 43 min with NIPPV. CONCLUSION:
      Similar to O2 long-term therapy in patients with COPD. NIPPV delivers in patients
      with kyphoscoliotic deformity a significant reduction of pulmonary artery
      pressure and increase of sleep quality.

PMID- 9235475
TI  - [Noninvasive ventilation of a 4-year-old boy with severe central late onset
      hypoventilation syndrome].
AB  - BACKGROUND: In the literature we found only five reports about noninvasive
      ventilation in cases with central hypoventilation syndrome. PATIENT AND METHOD:
      We report about a 4-year-old boy with severe late onset hypoventilation syndrome.
      During an interval of 3 months with nasal mask ventilation during sleep he showed
      an excellent cognitive and statomotoric development. After this time, he needed a
      noninvasive ventilation with a negative pressure system. RESULTS AND DISCUSSION:
      In our opinion, noninvasive nasal mask ventilation is a modern method in the
      treatment of patients with central hypoventilation syndrome. Tracheotomy is only
      necessary during the first year of life.

PMID- 9235476
TI  - [Primary alveolar hypoventilation in adulthood].
AB  - BACKGROUND: Central alveolar hypoventilation in an adult is characterized by
      dysfunction of the respiratory center in the brainstem and is very rare, seen
      mostly secondary to neurological lesions of the brainstem. CASE DESCRIPTION: We
      report a 48-year-old man with primary alveolar hypoventilation associated with
      marked cardiac arrhythmias and hemodynamic changes. Arterial blood gas analysis
      revealed daytime hypoxemia and hypercapnia not explained by normal pulmonary
      results. All night polysomnography showed sleep fragmentation following
      repetitive central apneas and hypoventilation with marked hypoxemia and the
      lowest saturation in REM sleep. Severe nocturnal hypoxemia was accompanied by
      marked hypercapnia. Premature ventricular complexes occurred associated with
      nocturnal hypoxemia in NREM sleep while sinus arrest of up to 11.3 s were only
      seen associated with hypoxemia in REM sleep. Pulmonary arterial pressures were
      normal when the patient was awake with marked increases in pulmonary arterial
      pressures associated with hypoventilation and changes in arterial oxygen
      saturation with the patient was asleep. CONCLUSION: Nasal positive pressure
      ventilation was effectively able to treat central apneas and hypoventilation,
      nocturnal hypoxemia and cardiac arrhythmias were no longer observed. Also,
      daytime arterial blood gases were normal with nocturnal nasal mechanical
      ventilation.

PMID- 9235477
TI  - [Effect of noninvasive ventilation on work of breathing in obesity].
AB  - BACKGROUND: Noninvasive ventilation with nose- or face-masks has been
      increasingly used in the past. The objective of mechanical ventilation is in
      addition to improve gas exchange to reduce breathing work. While improvement on
      breathing work has been shown mainly on normal-weight patients with different
      respiratory diseases, there is no existing data about the effect of noninvasive
      ventilation on the breathing work of patients with massive obesity. PATIENTS AND
      METHODS: Assisted mask-ventilation with bilevel positive airway pressure (BiPAP)
      was carried out on 5 overweight control subjects (overweight controls), 7
      overweight patients with obstructive sleep apnea (OSA), 6 patients with obesitas
      hypoventilation syndrome (OHS), and 7 overweight patients with chronic
      obstructive lung disease (COLD). Inspiratory pressure assist (IPAP) was set to 12
      or 16 cm H2O, exspiratory pressure (EPAP) was set to 5 cm H2O. All, subjects were
      massive overweight (body mass index [BMI] 42.2 +/- 5.8; range 31.8 to 55.4
      kg/m2). Respiratory muscle activity was measured as esophageal pressure change
      (delta Pes) and transdiaphragmatic pressure change (delta Pdi) and calculated as
      pressure time integral. RESULTS: With noninvasive ventilation respiratory muscle
      activity was significantly (p < 0.05) reduced in all groups at least 40% compared
      to baseline values during spontaneous respiration. CONCLUSIONS: Noninvasive
      ventilation via face masks can efficiently reduce work of breathing in subjects
      with massive obesity.

PMID- 9235478
TI  - [Follow-up of intermittent self-ventilation (ISB). Mortality and causes].
AB  - BACKGROUND: Intermittent positive pressure ventilation (IPPV) has an impact on
      morbidity and survival in patients with chronic respiratory failure. We analyse
      the causes of death in relation to the disease, the age, the effectiveness of and
      the compliance with IPPV. PATIENTS: The course of 108 patients, who were on IPPV
      for a mean of 24 (SD +/- 21) months, is analysed. RESULTS: Twenty-seven patients
      die (7/7 AIS, 2/17 muscular dystrophy, 8/45 kyphoskoliosis and TB sequelae, 2/7
      other neurological diseases, 6/16 COPD bronchiectasis, 1/1 fibrosis of the lang).
      The cause of death is in 21 hypoventilation or respiratory infection due to
      progressive disease (9 patients), air leakage after occlusion of tracheostoma (2
      patients), bronchitis (6 patients), discontinuation of IPPV (3 patients). Two
      patients develop pulmonary failure (atypical mycobacteriosis and asbestosis,
      pulmonary embolism). Non-pulmonary causes of death are present in 2 (rupture of
      aortic aneurysm, pleural carcinosis). CONCLUSIONS: A safe interface for IPPV is
      needed for longer survival. An efficient system of home-care has to be developed.

PMID- 9235479
TI  - [Pressure versus volume constant ventilation in chronic ventilatory
      insufficiency].
AB  - BACKGROUND: Volume controlled intermittent ventilation (IPPV) via face mask is a
      treatment of proven efficacy for chronic respiratory failure (CRF). Pressure
      support ventilation has recently been introduced in the treatment of CRF. In this
      study we investigated whether pressure constant ventilation (PCV) via face mask
      could be an adequate long term alternative to IPPV. PATIENTS AND METHODS: We
      studied 30 (24 male, age: 52.2 +/- 15.9 years) patients with CRF. We measured the
      following parameters at baseline, after 1, 2 and 6 months, respectively: blood
      gas analysis, oxygen saturation, vital capacity, forced exspiratory volume,
      breathing frequency, tidal volume, inspiratory mouth occlusion pressure, maximal
      inspiratory pressure, subjective symptom scores and ventilator acceptance scores.
      In all patients, we attempted to treat with IPPV over 1 month, followed by 1
      month's trial of PCV. If PCV, compared to IPPV, was adequate, PCV was continued
      for a follow-up period of 4 months' duration. If patients deteriorated after PCV
      they were treated the following 4 months with IPPV. RESULTS: In 28 out of 30
      patients CRF improved concerning subjective and objective parameters. After IPPV
      18 out of 28 patients changed to PCV, with an equal quality of treatment (PCV
      responder). Ten patients were PCV-nonresponders since compared to IPPV the
      subjective scores deteriorated and the PaCO2 increased again. In all patients of
      either therapy group, subjective and objective parameters remained constant for
      another 4 months period. At baseline the PCV-nonresponders had significantly
      higher degree of hypercapnia and oxygen desaturation; no other parameters were
      found to be of predictive value concerning the efficacy of PCV. CONCLUSIONS: PCV
      proved to be an alternative to IPPV in the treatment of chronic respiratory
      insufficiency in approximately 60% of the patients with CRF. However there is a
      subgroup with more severe CRF at baseline in whom PCV is inadequate.

PMID- 9235480
TI  - [Patient-related rejection of nasal IPPV therapy. Patients, reasons, follow-up].
AB  - PATIENTS: We retrospectively analysed the course of 33 patients who had rejected
      nasal IPPV-therapy (1988 to February 1996). RESULTS: The death-rate was higher
      (48%) compared to nasal IPPV patients in the same time (18%). The patients were
      divided in 3 main diagnostic groups (COPD, restrictive thoracic wall, neuromuscle
      disease). We observed the highest death-rate in COPD patients (66%) and the
      lowest death-rate in the group with scoliosis or chest wall disease (23%). This
      is the same result tendencially as in patients with nasal IPPV (mortality-rate
      COPD 66%, restrictive chest wall 6%).

PMID- 9235481
TI  - [Problems in adjustment to negative pressure ventilation].
AB  - We tried to establish a nasal intermittent positive pressure ventilation for a 54
      year old patient with post-polio kyphoscoliosis. Due to intractable rhinitis the
      patient stopped the treatment. A negative pressure ventilation via a cuirass
      exhibited an inverse ventilation: during the inspiratory cycle of the ventilator
      the diaphragm was elevated and the patient was forced to exhale, afterwards he
      needs to inhale by himself. The ventilatory support is now done via a combined
      nasal-mouth mask and intermittent positive pressure ventilation.

PMID- 9235482
TI  - [Present status and future aspects of the respiratory pacemaker].
AB  - Under certain conditions, phrenic pacing is a rare but most effective and
      attractive alternative for long-term ventilation. General indications concern
      diseases of the breathing center, for example Undine's disease (loss of CO2
      sensitivity) in infants and high cervical spinal cord lesions in the level of C0
      to C3. Despite of the advantage of physiologic respiration mode (no positive air
      pressure) compared to long-term ventilation, the phrenic pacemaker enables high
      life quality for the patients due to possibilities of closing of tracheostoma
      (Vienna system), an optimum in mobility and high cost effectiveness.
      International research and development in this area concerns 1. nerve
      transposition of an innervated nerve to a denervating phrenic nerve, 2.
      additional stimulation of thoracal muscles for inspiration, 3. additional
      stimulation of expiration, 4. endoscopic operative positioning of the electrodes,
      5. development of a pacer with sensor input for an individual respiration rhythm
      (controlled by the vocal cord) and 6. development of a fully implantable system
      Improvements of the present pacemaker system may lead to enlargement of
      indications, for example use in patients with severe nocturnal arrhythmias in
      respiration.

PMID- 9235483
TI  - [Dynamics of pressure and flow curves of various expiratory pressure valves].
AB  - BACKGROUND: Flow dynamics of exhalation valves in home care ventilators (CPAP-,
      BiLevel-, and autoadjust machines) are determined by their physical properties.
      The flow characteristic implies distinct curves leading to expiratory increase
      and inspiratory decay of pressure depending on flow rate. MATERIAL AND METHODS:
      For examination of pressure/flow characteristic we examined several valves (one
      and two circular holes, Sullivan-, Whisper-Swivel-, Silence-valve). Expiratory
      peak and inspiratory trough assessed at constant pressure (10 mbar) were measured
      with varying flow rates. RESULTS: Valves differ with their pressure
      characteristics up to 1.2 mbar for inspiratory and 1.0 mbar for expiratory flow
      at 2.0 1/s. CONCLUSION: The specific characteristic for each valve is part of the
      total efficiency of a home care ventilator. Their pressure flow relationship has
      to be taken into account for titration process and for exchange between different
      machines and accessories.

PMID- 9235484
TI  - [Work of breathing in noninvasive proportional assist ventilation in patients
      with respiratory insufficiency].
AB  - BACKGROUND: The aim of the present study was to evaluate if Proportional Assist
      Ventilation (PAV), when applied noninvasively via face mask, can reduce
      ventilatory effort in patients with respiratory failure. We present preliminary
      results of an ongoing study. PATIENTS AND METHODS: In 5 patients with respiratory
      failure due to different underlying disorders (pulmonary fibrosis, bilateral
      diaphragm paralysis, COPD) we compared the transdiaphragmal pressure-time
      integral. PTdi (integral off Pdi dt) after 15 minutes of noninvasive PAV to the
      baseline values without ventilatory support. RESULTS AND CONCLUSION: Four
      patients showed reduction of PTdi to various extend. One patient who presented
      low diaphragmal activity at baseline due to diaphragmal paralysis showed a slight
      increase in PTdi during ventilation. Mean PTdi decreased by 26.7%. PaCO2 in the 5
      patients showed no significant change after 15 minutes of ventilation, thus
      indicating that with noninvasive PAV patients can maintain constant ventilation
      with reduced effort.

PMID- 9235485
TI  - [Managing life and death wishes of invasively ventilated amyotrophic lateral
      sclerosis patients].
AB  - BACKGROUND: Find of life decisions of patients with amyotrophic lateral sclerosis
      and respiratory failure are influenced by several environmental factors. PATIENTS
      AND METHODS: We describe the course of disease and decision making of four of
      these patients. RESULTS: Most decisions have been inconsistent and were seen to
      be depending on actual situations. Main factors were: 1. preclinically (before
      respiratory failure) medical information, 2. during respirator dependency in the
      hospital's intensive care unit the clinical setting and the individual
      perspective depending on the patient's private situation, 3. at home ventilation
      the family's situation and conflicts. Especially the patients requests for
      disconnection from the respirator overtaxed their carers capacities. CONCLUSION:
      We conclude that there is need for professional psychosocial intervention for the
      patients and their families.

PMID- 9235486
TI  - [Prospective study of the quality of life in intermittent self-ventilation].
AB  - PATIENTS AND METHOD: We assessed quality of life for 17 patients (age 14 to 74
      years) before and during intermittent (nightly) nasal home mechanical ventilation
      with a standardized questionnaire (SF 36, Medical Outcomes Trust, Boston, USA).
      Underlying diseases were amyotrophic lateral sclerosis, bronchiectasis,
      kyphoscoliosis, pulmonary emphysema, muscular dystrophy and sequelae of
      tuberculosis. Blood gas and lung function data were collected during every
      examination. RESULTS: We observed statistically significant increases for items
      of general health, mental health, vitality and capillary oxygen partial pressure.
      CONCLUSION: The SF 36 allows to assess quality of life for patients under
      intermittent mechanical ventilation at home.

PMID- 9235487
TI  - [Quality of life in home ventilation].
AB  - BACKGROUND: The purpose of this study is to assess quality of life in patients
      with chronic respiratory failure who require home mechanical ventilation (HMV).
      PATIENTS AND METHODS: Patients with COPD (n = 20), scoliosis (n = 20),
      neuromuscular diseases (n = 20) and others (n = 7) were examined. A specific
      questionnaire containing forms for the patient, the physician and for the
      relatives was developed according to the formulation of the question (Fragebogen
      zur chronischen Heimbeatmung = FCH, Interview zur chronischen Heimbeatmung =
      ICH). In addition to that the Hospital Anxiety and Depression Scale (HAD) and the
      Asthma Quality of Life Questionnaire were used. Arterial blood gas tensions,
      pulmonary function and inspiratory mouth occlusion pressure were studied.
      RESULTS: Quality of life in patients with scoliosis and neuromuscular diseases is
      improved during HMV compared to patients with COPD who especially are impaired
      with regard to psychological and functional conditions. Correlations with
      physiological parameters and with the compliance could not be observed.
      CONCLUSION: Despite progression of the disease HMV enhances quality of life in
      patients with scoliosis and neuromuscular diseases. The outcome in COPD is less
      evident. Therefore the indication must be considered more critically.

PMID- 9235488
TI  - [Study of electroretinogram components using pattern inversion in the early
      diagnosis of glaucoma].
AB  - Current electrophysiological techniques that help guide the diagnosis of glaucoma
      include pattern-electroretinogram (PERG) and pattern-visual evoked potential
      (PEVP) recordings. However, PERG has been recognized over the last decade as a
      good indicator of retinal ganglion cell function. One hundred seventy one eyes
      corresponding to 89 subjects were studied using both PERG (gold foil electrodes)
      and PEVP recordings. Two groups respectively including 32 subjects with ocular
      hypertension (OHT) and 27 subjects with simple chronic glaucoma (SCG) were
      compared with a control group composed of 30 healthy age-matched subjects. In
      regard to PERG recordings, the amplitudes of the P50 and N95 components were
      measured, but statistically significant differences were shown only for the N95
      amplitudes both SCG (P < 0.01) and OHT (P < 0.05) groups. The amplitude and
      latency of the PEVP P100 component were analyzed. P100 latency was significantly
      delayed (P < 0.05) in SCG patients only. These findings suggest that the
      amplitude of the N95 component is the most sensitive electrophysiological
      parameter for early glaucoma detection.

PMID- 9235489
TI  - [Intraventricular hemorrhage and parenchymatous ischemia in the newborn at term.
      Report of five cases].
AB  - Although intraventricular hemorrhage associated with cerebral ischemia without
      severe perinatal asphyxia is rare in full-term newborns, it can be severe, have
      early or late onset depending on the etiology and be of poor prognosis. Five full
      term neonates (37 to 41 weeks of gestational age) without criteria of severe
      perinatal asphyxia were admitted to the intensive care unit for seizures: four
      were between seven and 11 days of age and one was only 12 h old. Clinical or
      electroclinical seizures recorded by continuous EEG monitoring were numerous,
      leading to status epilepticus in three babies. They were unilateral (at the level
      of the left hemisphere) in one infant and have not been recorded in the fourth
      case. Past-ictal EEG abnormalities were numerous rolandic or temporal slow or
      fast sharp waves of variable polarity. Cranial CT scans showed uni- or bilateral
      intraventricular hemorrhage with dilatation and subcortical or periventricular
      ischemic lesions with hemorrhage. Four out of the five infants died during the
      neonatal period.

PMID- 9235490
TI  - [Syncope or epileptic attack?].

PMID- 9235491
TI  - [Proprioceptive and cutaneous evoked somatosensory potentials in the baboon:
      cycles of GABAergic excitability and inhibition].
AB  - Double stimulations induce deep and long-lasting inhibition (0-300 ms) of the P16
      N30 components of somatosensory potentials (SEP) evoked by sciatic or sural nerve
      stimulation. This inhibition is evidenced on both S1 and M1 cortical areas,
      demonstrating similar course and duration, whatever the source (right or left
      limb) and/or the modality (extero- or proprioceptive) of conditioning and testing
      afferences. The depth of this inhibition depends on the relative amplitude of the
      conditioning to testing SEP. After muscle injection of a subconvulsive dose of
      bicuculline, tSEPs are facilitated when individually elicited. When double
      stimulations are used, the inhibition of the SEP test is sharply reduced (with a
      30-ms interstimulus delay). However, disinhibition of the conditioned SEP does
      not depend on separate individual SEP facilitations. Cortical GABAergic type a
      circuits are likely to be involved in inhibition of the conditioned SEP. This
      inhibition would be a non-invasive image of inhibitions that preserve the
      specificities of sensory messages in primary areas.

PMID- 9235492
TI  - Cervical dystonia: the initial presentation of Huntington's disease?

PMID- 9235493
TI  - A randomized trial of enhanced therapy for early syphilis in patients with and
      without human immunodeficiency virus infection. The Syphilis and HIV Study Group.
AB  - BACKGROUND: Reports of neurosyphilis and invasion of cerebrospinal fluid by
      Treponema pallidum in patients with human immunodeficiency virus (HIV) infection
      have led to doubts about the adequacy of the recommended penicillin G benzathine
      therapy for early syphilis. METHODS: In a multicenter, randomized, double-blind
      trial, we assessed two treatments for early syphilis: 2.4 million units of
      penicillin G benzathine and that therapy enhanced with a 10-day course of
      amoxicillin and probenecid. The serologic and clinical responses of patients with
      and without HIV infection were studied during one year of follow-up. RESULTS:
      From 1991 through 1994, 541 patients were enrolled, including 101 patients (19
      percent) who had HIV infection but differed little from the uninfected patients
      in their clinical presentations. The rates at which chancres and rashes resolved
      did not differ significantly according to treatment assignment or HIV status.
      Serologically defined treatment failures were more common among the HIV-infected
      patients. The single clinically defined treatment failure was in an HIV-infected
      patient. Rates of serologically defined treatment failure did not differ
      according to treatment group (18 percent at six months with usual therapy; 17
      percent with enhanced therapy). T. pallidum was found at enrollment in the
      cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of
      35 patients tested. None had clinically evident neurosyphilis, and the rate of
      detection of T. pallidum did not differ according to HIV status. CONCLUSIONS:
      After treatment for primary or secondary syphilis, the HIV-infected patients
      responded less well serologically than the patients without HIV infection, but
      clinically defined failure was uncommon in both groups. Enhanced treatment with
      amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was
      detected in cerebrospinal fluid before therapy in a quarter of the patients
      tested, such a finding did not predict treatment failure. The current
      recommendations for treating early syphilis appear adequate for most patients,
      whether or not they have HIV infection.

PMID- 9235494
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 24-1997. A six-year-old boy with bouts of abdominal pain,
      vomiting, and a left-sided abdominal mass.

PMID- 9235495
TI  - Managed care in the crystal ball.

PMID- 9235496
TI  - Managed care in the crystal ball.

PMID- 9235497
TI  - Managed care in the crystal ball.

PMID- 9235498
TI  - Managed care in the crystal ball.

PMID- 9235499
TI  - Solid cancers after bone marrow transplantation.

PMID- 9235500
TI  - Radiotherapy for rectal cancer.

PMID- 9235501
TI  - Radiotherapy for rectal cancer.

PMID- 9235502
TI  - Radiotherapy for rectal cancer.

PMID- 9235503
TI  - Transmission of the human immunodeficiency virus and the hepatitis C virus.

PMID- 9235504
TI  - The management of hypertrophic cardiomyopathy.

PMID- 9235505
TI  - Familial atrial fibrillation.

PMID- 9235506
TI  - Anaphylaxis with Anisakis simplex in the gastric mucosa.

PMID- 9235507
TI  - [Evaluation of treatment outcome in patients after extremely severe head injury
      (GCS 3-4)].
AB  - Advances in the diagnosis and treatment of severe head injured patients (GCS < =
      8) have led to major improvement in outcome, but have not eliminated high
      mortality rates, which range between 38 and 80% as reported in the literature.
      The aim of this study was to evaluate the outcome of patients with GCS 3 and 4
      and to evaluate the role of early and late hypotension (systolic blood pressure
      SBP < 90 mmHg) in outcome. Sixty two patients with severe head injury were
      divided into two groups. In Group I-22 patients with GCS 3-4, and in Group II-40
      patients with GCS 5-8. There was no significant difference between mortality (p =
      0.5), poor outcome (p = 0.36), and the very best outcome in the groups (p =
      0.06). There was a statistically significant difference in death rate (p =
      0.0012), when hypotension was present at the scene. Our data suggest that
      patients with extremely severe head injury do not necessarily have a worse
      outcome, if prompt diagnosis and appropriate aggressive treatment is implemented.

PMID- 9235508
TI  - [Changes in blink reflex (OM) after lesions of the nervous system in various
      locations].
AB  - Electrically evoked blink reflex (BR) as a one of the non-invasive methods is
      used to diagnose function of central nervous system, specially of brainstem. It
      seems that this method is not fully appreciated in neurological practice. On the
      basis of literature and own experience the authors present typical pictures of BR
      on EMG analysis related to the lesions of respective parts of reflex arc and
      suprasegmental structures involving pyramidal and extrapyramidal tracts.

PMID- 9235509
TI  - [Hemi-neglect syndrome. Clinical characteristics and reeducation management].
AB  - The paper deals with hemi-neglect disorders which may occur in patients with
      right hemisphere lesions. Apart from description of the clinical symptomatology,
      with emphasis on the features most significant for the differential diagnosis,
      methods of neuropsychological rehabilitation were discussed.

PMID- 9235510
TI  - [Complications after surgery of the anterior cervical spine].
AB  - Every year several thousands of operations on the cervical spine from anterior
      approach are performed in the world for decompression of spinal cord and nerve
      roots. It is estimated that in 0.2 to 12% of the operations serious
      intraoperative and postoperative complications occur. Such cases have been
      reported in the world literature but in scant numbers. The authors discuss early
      and late complications after operations on the cervical spine connected with the
      surgical method.

PMID- 9235511
TI  - [Hemi-neglect syndrome--case report].
AB  - A female patient with an ischaemic focal lesion in the non-dominant cerebral
      hemisphere due to stenosis of the right carotid artery is presented. Besides a
      mild left hemiparesis the clinical symptomatology included a pronounced hemi
      neglect syndrome in the form of unilateral limb akinesia, a failure to respond to
      stimuli presented to the left of the midline as well as anosognosia and
      anosodiaphoria. Despite the 6-week rehabilitation training, the neglect syndrome
      was rather stabilized with only a slight tendency for improvement.

PMID- 9235512
TI  - [Guillain-Barre syndrome with an especially severe course].
AB  - A case of polyradiculoneuritis in a 51-year-old man is reported. Symptoms
      occurred suddenly. Our serologic tests failed to explain the cause of the
      illness. Physical examination showed tetraplegia and respiratory muscles
      paralysis which required continuous use of respirator during six weeks. In the
      treatment were used: steroid hormones, antibiotics, anabolics, plasmapheresis. In
      physical treatment: kinesitherapy, massage, electrotherapy, hydrotherapy. After
      three years of intensive physical treatment patient was cured.

PMID- 9235513
TI  - [Diversity in the clinical course of toxoplasma encephalitis in two patients
      infected with human immunodeficiency virus (HIV)].
AB  - The central nervous system (CNS) is the most common site of Toxoplasma gondii
      infection in HIV-positive patients, mainly due to reactivation of Toxoplasma
      cysts. The diagnosis is difficult since no sensitive and specific non-invasive
      diagnostic tests exist. The patient may present with rather unspecific signs and
      symptoms. We present atypical course of CNS-toxoplasmosis in two HIV-positive
      persons.

PMID- 9235514
TI  - [Surgical approach to cranial base and craniofacial tumors].
AB  - Skull base tumour is rare and until recently was considered unresectable. The
      authors present a patient with skull base tumour of extra and intracranial
      compartment penetrating into parapharyngeal space and maxillary bone. Radiologic
      findings on CT, MRI, arteriography were studied. A surgical technique to expose
      the cranial base and intraoperative findings are described. Significant
      improvement occurred after incomplete tumour resection.

PMID- 9235516
TI  - [Intracerebral hematoma].

PMID- 9235515
TI  - [Posttraumatic carotid-cavernous fistula: diagnosis and treatment--exemplified by
      a patient with a fistula following a blunt head injury].
AB  - Carotid-cavernous fistula is a rare posttraumatic complication. The authors
      described the patient in which a blunt cranial injury caused the carotid
      cavernous fistula. In diagnosing the fistula Doppler examination proved very
      helpful. It showed the vein-arterial flow in the ophthalmic artery on the fistula
      side. The arteriography of the common carotid artery fully confirmed the
      diagnosis. Successful treatment was achieved by means of percutaneous
      endovascular balloonization of the fistula ring.

PMID- 9235517
TI  - [Subclasses of IgG in patients with neurosyphilis].
AB  - IgG subclasses levels in the CSF and sera were measured in 15 patients with
      neurosyphilis. Intrathecal IgG and IgG subclasses synthesis was studied as well.
      There was an elevation of IgG1 and IgG3 subclasses in the CSF and IgG1 elevation
      in the sera of patients with neurosyphilis. General IgG index was elevated in 46%
      of the patients. This was due mainly to IgG1 and IgG3 intrathecal synthesis.
      Oligoclonal IgG bands were present in the CSF in seven out of 15 studied
      patients. These results may be helpful in the first stage of the diagnostic
      procedure before specific serological tests are performed.

PMID- 9235518
TI  - [Neurologic signs in Addison-Biermer disease (report of 3 cases)].
AB  - The authors report three patients in whom a neurological syndrome was the first
      manifestation of Addison-Biermer disease. In the first case a paraneoplastic
      neurological syndrome was suspected, in two other cases the initial tentative
      diagnosis was multiple sclerosis. The correct diagnosis was reached after a
      prolonged diagnostic procedure and after ruling out of other diseases. The course
      of the disease was very serious in all cases leading to death of one patient
      despite intensive treatment (postmortem examination confirmed the diagnosis). In
      the second case the neurological syndrome failed to regress completely. The
      authors stress the necessity of considering this aetiology in neurological
      syndromes of atypical pattern and course.

PMID- 9235519
TI  - [Morphologic analysis of of microglia in astrocytomas].
AB  - Forty human primary brain astrocytoma tumours (anaplastic and non anaplastic)
      were subjected to correlative light and electron microscopic studies of microglia
      in tumour tissue and in its surroundings. It was found that a great number of
      microglia cells were present in the all types of astrocytomas. In the non
      anaplastic tumours (fibrillary, protoplasmic, gemistocytic) ramified microglia
      mostly was observed. In glioblastomas and anaplastic astrocytomas the greatest
      number of ameboid microglia and very rarely ramified microglial cells were found.
      It is suggested that the differences between the various kinds of astrocytomas
      determine the difference in the type of microglial reaction. It is assumed that
      this might be caused by the differences in secreting some factors by these tumour
      astrocytes.

PMID- 9235520
TI  - [Segmental conduction times in motor pathways for the soleus muscle--methodology
      and normal values].
AB  - The study performed in 30 normal subjects (24F, 6M) with age range 18-55 years
      and height range 154-188 cm. Electrical stimulation was applied to the tibial
      nerves and direct response M and F-wave was recorded from right and left SOLEUS
      (60 examinations). Transcranial and paravertebral (S1 level) magnetic stimulation
      was applied with simultaneous recording of responses from both SOL. A software
      system was developed which permitted the redout of parameters (latencies and
      amplitudes) from Mystro device, calculation of the derived parameters (segmental
      motor conduction times) and classification of results according to 95% confidence
      intervals for the parameters obtained in the group of normal subjects included in
      the study. Report form was prepared which on line gave the results of individuals
      examinations. The fast and painless investigation should prove useful in
      electrophysiological diagnosis of motor pathway function including the entire
      length.

PMID- 9235521
TI  - [Evaluation of perceptive activity in persons with low pressure hydrocephalus
      treated surgically. Preliminary report].
AB  - Preliminary assessment of perceptive activity was carried out in patients with
      low-pressure hydrocephalus diagnosed clinically. The purpose of the study was
      establishing of the valuable tests for the neuropsychological diagnosis making
      possible finding of perceptive processes most frequently disturbed in low
      pressure hydrocephalus. The studied group comprised 53 patients operated on for
      this hydrocephalus. In only 9 cases the condition of the patient made possible a
      detailed study of the perceptive processes. In this group the tests were carried
      out three times: before, immediately and after a longer time after insertion of
      ventriculoperitoneal shunt. The results showed differences in the level of
      general perceptive functioning in the whole group. In the subgroup studied in
      detail no general perception deterioration was found, and the usual disturbances
      were noted in the memorization of new information and in visuospatial
      orientation. Late after the operation the greatest improvement was observed in
      the most disturbed functions.

PMID- 9235523
TI  - [Behavior of some acute phase proteins in blood of patients with acute vascular
      brain damage in the earliest period of the disease].
AB  - The aim of this study was to determine the levels of some of the acute phase
      proteins (APP) in patients suffering from acute cerebral vascular diseases in the
      earliest period of the disease. Studies were performed on 95 persons. The levels
      of the C-reactive protein, fibrinogen and the component C3 of complement in blood
      were measured using the radial immunodiffusion technique. Increased level of
      acute phase proteins (APP) was found in patients with cerebral infarct and
      intracerebral haemorrhage. There was no significant increase of the APP level in
      patients with transient ischaemic attack.

PMID- 9235522
TI  - [Intracranial chordomas; histochemical and immunohistochemical examinations].
AB  - Chordoma is one of rare intracranial neoplasms (0.2-0.5%). Apart from classic
      chordoma in 1973 r. Heffelfinger and al. separated chondroid chordoma which
      showed better prognosis. We studied 4 classic and 3 chondroid intracranial
      chordomas. All tumours contained chondroitine sulfate and keratan sulfate and
      showed positive immunohistochemical reactions to cytokeratin, S-100 protein and
      vimentin, supporting the concept of common origin of both types of chordomas.
      Immunohistochemical studies of PCNA and Ki-67 antigen and staining AgNOR's did
      not show significant differences in the proliferative activity between both types
      chordomas what attests to biological malignancy.

PMID- 9235524
TI  - [Diagnostic value of hematopoietic stem cells].
AB  - Proliferation and differentiation of the haemopoietic stem cell are critical for
      the maintenance of normal haemopoiesis, damage to haemopoiesis, onset of
      malignant haemopoiesis and repopulation of haemopoiesis after bone marrow
      transplantation. To evaluate the actual state of haemopoiesis a quantitative
      assay of haemopoietic stem cells would be needed. Morphology of haemopoietic stem
      cells cannot be detected by their microscopic morphology. In human practice no
      stem cell assay is available, therefore, the quantity of human pluripotent stem
      cells is characterised by the frequency of the progenitors differentiating into
      erythrocyte, granulocyte or macrophage cell lines (CFU-GEMM, BFU-E, CFU-GM, CFU
      Meg). Progenitor cells, can be easily tested by their ability to form in vitro
      colonies in soft gel cultures in the constant presence of the specific regulator
      of the cell line ("colony stimulating factor" = CSF). Seven-14 days after
      explantation of haemopoietic cells colonies containing 40 to 1000 cells are
      formed. These colonies are proved to be of clonal origin. The quantitative assay
      of colony forming progenitors has a critical significance in haematological
      diseases due stem cell damage and bone marrow transplantation. The present paper
      deals with the diagnostic value of progenitor assays.

PMID- 9235525
TI  - [Gallbladder hypomotility in diabetic polyneuropathy].
AB  - A study was made of the pathogenic role of gallbladder hypomotility, which is
      presumably responsible for the high incidence of gallstone disease in long
      standing diabetes mellitus. The gallbladder motility of diabetic patients (n =
      10) was measured by means of quantitative hepatobiliary scintigraphy, and the
      severity of concomitant autonomic and sensory polyneuropathy was determined. The
      presence of marked gallbladder hypomotility was proven, and a positive
      correlation was observed between the severity of autonomic neuropathy and the
      contractile disorder. In this group of diabetic patients, a hypaesthetic sensory
      polyneuropathy too was recognized, the degree of which exhibited a positive
      correlation with the autonomic neuropathy score. This study underlines the
      important role of the autonomic neural dysfunction in the development of
      gallbladder hypomotility accompanying long-term diabetes mellitus.

PMID- 9235526
TI  - [Acetone metabolism: biochemistry, toxicology and clinical implications].
AB  - In the article, the routes of acetone metabolism are summarized and the
      conditions in which acetonemia occurs, are taken into account. Acetonemiae are
      classified as to be of exogenous and endogenous origin, and the biochemical
      mechanisms of the development of different acetonemiae are analyzed. Referring to
      the medical significance of acetone and isopropanol it is suggested that the
      previous view on those should be revised. As a summary, a hypothesis is raised
      according to which the physiological role of acetone production would be, on the
      one hand, to regulate the pH buffering capacity of body fluids and, on the other
      hand, in ketotic states emerging in diseases, to provide additional fuel for the
      particularly sensitive tissues (e.g. brain).

PMID- 9235527
TI  - [Reproducibility of malignancy grading in prostatic cancers using the Gleason
      Bockling system].
AB  - Histologic slides from 50 cases of prostatic adenocarcinoma were evaluated by 5
      pathologists, in order to test the reproducibility of grading in two systems.
      Twenty-five needle core biopsies and 25 surgical (adenomectomy) specimens were
      graded in two sessions, according to the histomorphologic criteria of Gleason and
      Bocking. The results were analyzed by the kappa statistics. In surgical
      specimens, there were no significant differences in the interobserver
      reproducibility of microscopically assessed categories. In needle biopsies,
      however, Gleason's primary pattern (62%, kappa = 0.42), and Bocking's
      histological pattern (63%, kappa = 0.37) showed the highest level of agreement.
      Among the computed (derivated) classification terms, those consisting of only 3
      groups (Gleason grouping, kappa = 0.39; Bocking grade, kappa = 0.39) proved to be
      better reproducible than the corresponding score values (p < 0.05). When
      compressing both systems into two grades (high and "non-high"), reproducibility
      was improved (kappa = 0.52). For a substantial improvement of grading results,
      more accurate grade definitions, continuing training and regular consultation of
      pathologists are necessary. Based on the results obtained by intraobserver
      analysis we conclude that kappa statistics is of limited value when analyzing the
      role of individual experience at grading reproducibility.

PMID- 9235529
TI  - [Analysis of normality of data on the basis of the mean and standard deviations].
AB  - In this study the author shows a method for the supervision of normal
      distribution on the basis of the mean and the standard deviation. The given
      method can be used to control the data of the scientific articles and the
      clinical data from normal distribution point of view.

PMID- 9235528
TI  - [Prenatal determination of fetal RhD-positivity from the blood of the RhD
      negative mother].
AB  - It is reported on a prenatal determination of fetal RhD blood group from blood of
      a sensitized RhD-positive mother at 11th week gestation. The result was confirmed
      by a subsequent amplification of fetal DNA obtained by chorionic villus biopsy.
      It is supposed that in sensitized pregnancies the high number of fetal RhD
      positive red blood cells in maternal blood is enough to be detectable by
      polymerase chain reaction.

PMID- 9235530
TI  - [The bioavailability of endogenous calcitonin under selective pharmacological
      sympathectomy].
AB  - The serum concentrations of calcitonin (CT) and sublemmal granule numerical
      density in the thyroid C-cell basal polus cytoplasm were measured in guanethidine
      sympathectomized rats aged 2 weeks. Based on the previously proposed procedure
      [Krasnoperov et al. 1997], the confidence interval of endogenous CT
      bioavailability was found to be 52-100% (p > or = 0.95). It significantly
      differed from the similar control parameter (73-100%). The findings suggest that
      it cannot be excluded that unlike normal animals, sympathectomized 2-week rats
      may have CT retention at the transinterstitial and/or transmural stages of hemato
      C-cellular mass-transfer.

PMID- 9235531
TI  - [Patterns and the role of changes in the sympathetic and parasympathetic
      regulation of the heart in local ischemia and reperfusion].
AB  - Modelling of transient coronary insufficiency on 480 conscious and unconscious
      non-inbred albino mate rats during 10-, 40-, or 120-min coronary occlusion,
      followed by 40-60-min myocardial reperfusion revealed characteristic changes in
      the sympathetic and parasympathetic mechanisms of cardiac regulation. According
      to the extent and duration, 3 phenomena were identified, which were of mainly
      adaptive or pathogenic significance. These included: 1) replacement of the
      domination of sympathetic influences on the heart by the predomination of
      parasympathetic effects; 2) development of hormonal and neuromediator
      dissociation of catecholamine levels in the heart; 3) regulation-restricted
      cardiac participation in systemic hemodynamic responses. The predomination of
      adaptive effects of the above phenomena caused a reduction in the ischemic and
      reperfusion alteration of the heart and potentiated its reparative processes.
      With progression and more prolonged duration of these phenomena there is an
      additional myocardial regulatory alteration.

PMID- 9235532
TI  - [The cardioprotective action of the anticonvulsant preparation sodium valproate
      in disorders of cardiac contractile function caused by acute myocardial infarct
      in rats].
AB  - The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on
      cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt)
      were studied in rats having 2-day myocardial infarction (MI). The postinfarction
      rather than preinfarction use of SV substantially restricted the depressed
      resting left ventricular function. Given by two regimens, SV increased cardiac
      resistance to the maximum isometric load induced by 60-sec ligation of the
      ascending aorta. The cardioprotective effect of the drug was shown due to its
      positive chronotropic action rather than its inotropic one. Thus, SV may be used
      as an effective drug for the prevention and treatment of postinfarct cardiac
      dysfunctions.

PMID- 9235533
TI  - [Cardiac phospholipids in the dynamics of experimental myocardial infarct in
      rats].
AB  - The study was undertaken to examine the cardiac levels and composition of
      phospholipids (PL) in the time course of rat experimental myocardial infarction
      (EMI) caused by the Selye procedure. The course of EMI was shown to be
      accompanied by a rise in the total levels of PH in the cardiomyocytic membranes,
      which was observed 1 hour and 14 days after the occurrence of EMI. Analyzing the
      composition of individual PL demonstrated higher concentrations of the minor PL
      phosphatidylserine and phosphatidylinositol, as well as differently directed
      changes in the content of massive PL: lower concentrations of
      phosphatidylethanolamine and higher levels of phosphatidylcholine. The pattern of
      the found changes altered in relation to the duration of EMI. By and large, the
      revealed changes reflect the processes of transbilayer redistribution of PL,
      alterations in their physicochemical properties and in the rate of lipid
      peroxidation occurring in the membranes.

PMID- 9235534
TI  - [The chronocorrection of disorders in the blood coagulation rhythm with kurantil
      in patients with decompensated rheumatic heart defects].
AB  - The circadian pattern of hemocoagulation was studied in patients with
      decompensated rheumatic heart disease (DRHD) concurrent with stages I-II
      circulatory failure (CF) during complex treatment or medical treatment with
      disaggregants. Biorhythmological studies demonstrated that in patients with DRHD
      and CF chronotherapy with curantyl had some advantages over the traditional
      therapy during complex drug therapy. In these patients, the chronopatterns of
      circadian rhythms of hemocoagulative parameters tended to normalize under the
      influence of curantyl chronotherapy, by diminishing the signs of external
      desynchronization. Advantages of chronotherapy over the traditional treatment
      found in patients with DRHD and stages I-II CF, as manifested by its clinical
      effect in shorter periods (on days 4-5) when small daily and course doses of the
      drug were used. Based on the biorhythmological studies of hemostatic parameters,
      a method of curantyl chronotherapy was developed for patients with DRHD and
      stages I-II CF, which may optimize the therapeutical process in patients with
      this abnormality.

PMID- 9235535
TI  - [Immune system cells as mediators in the reaction of other body systems to stress
      exposure].
AB  - This paper first details an acute reaction of mice to the administered syngenic
      and allogenic live splenocytes from the animals exposed to great emergency. The
      authors have called it "nonspecific immunogenic shock" as its stages and
      manifestations which are characteristic of shock are caused only by lymphocytes,
      but associated with any specific exposure. The most common sequela of nonspecific
      immunogenic shock may be animal's death within minutes or first days after
      administration of splenocytes. In this case, marked cataracts (generally after
      death, but occasionally in life) appear both in recipients and stress-exposed
      donors. The ability of splenocytes activated by stress in donors to cause sudden
      or delayed death of most recipients makes the author give the second term of
      "death transfer" to nonspecific immunogenic shock.

PMID- 9235536
TI  - [Dysregulation of the immunological mechanisms and phagocytic activity of the
      leukocytes--the leading cause of acute inflammation].
AB  - The paper provides evidence for the assumption that the leading cause of acute
      odontogenic inflammatory processes of the face and neck is immunological
      deficiency which initiates the spread of infection from the radix dentis into
      cellular spaces. The type of inflammation (normo-, hyper-, or hypoergic) mainly
      depends upon the responsiveness of the phagocytic system. This conclusion is
      supported by the results of nonspecific and immunological correction made in
      patients.

PMID- 9235537
TI  - [Modern pathophysiology: its status and outlook].

PMID- 9235538
TI  - [A chemiluminescent analysis of the functional activity of the blood leukocytes
      in children with recurrent obstructive bronchitis and atopic dermatitis].
AB  - To study the informative value of chemiluminescence determination of leukocytic
      functional activity, children aged 3 to 6 years who had recurrent obstructive
      bronchitis (ROB) and atopic dermatitis (AD) were examined. The mean statistic
      data on spontaneous and induced chemiluminescence responses were found to be far
      from fully reflecting the individual characteristics of leukocytic functional
      activity in children with these diseases (in a group of patients with the same
      disease, children were found to have lower and higher values of cell
      chemiluminescence). This suggests that in developed infection, the functions of
      phagocytic cells may be not only activated, but also suppressed. Two cases of
      using the chemiluminescence technique during treatment of children with ROB and
      AD are given as an example.

PMID- 9235539
TI  - [The effect of selenium on free-radical oxidation processes in the bone
      regenerate after a fracture].
AB  - The paper presents the results of examining the central part of the rat mandible
      for a month after its fracture. The rate of free radical oxidation was estimated
      by the levels of diene conjugates (DC), malonic dialdehyde (MDA) and by the
      activity of selenium-containing glutathione peroxidase (GPO). The findings
      suggest that there are profound injury-induced changes in free radical oxidation
      and antioxidative defense. The levels of DC and MDA showed the maximum upward
      change as a double-peaked curve and longer restoration to the level seen in
      control animals. These rats had the minimum enhanced GPO activity. In the animals
      receiving intragastric selenium methionine or selenium electrophoresis applied to
      the site of mandible fracture, alterations in DC and MDA were less pronounced and
      GPO showed a higher activity.

PMID- 9235540
TI  - [The blood gas-transport function in patients with iron-deficiency anemia under
      measured physical loading].

PMID- 9235542
TI  - [The mechanisms of the cardioprotective action of the n-3 class of
      polyunsaturated fatty acids].

PMID- 9235541
TI  - [The effect of urea on the course of experimental uremia in rats with a subtotal
      nephrectomy].
AB  - The important role of increasing plasma urea levels in renal failure progression
      was shown in Wistar rats with experimental uremia induced by subtotal
      nephrectomy. Renal structural lesions and dysfunction were the same as in rats
      fed a high-protein diet and in those on a low-protein diet supplemented with
      urea. The changes were much less in the control group of rats fed a low-protein
      diet alone. The findings suggest that high blood urea concentrations appear to be
      a cause of intraglomerular hemodynamic disturbances following renal failure
      progression.

PMID- 9235543
TI  - [The effect of serotonin antibodies on the development of a neuropathic pain
      syndrome].
AB  - Serotoninergic and catecholaminergic neurotransmitter systems of the brain play
      an important role in the regulation of pain sensitivity. However, there are no
      data on the involvement of antibodies to the above neurotransmitters is the
      development of neuropathic pain syndromes. The authors' studies indicated that
      the development of neuropathic pain syndrome occurring after nerve damage is
      followed by the formation of serotonin antibodies and their enhanced induction
      caused by immunization of animals with serotonin-protein conjugated antigen
      aggravates the pain syndrome. Block and insufficiency of the serotoninergic
      antinociceptive system may be a cause of the progression of the pain syndrome due
      to serotonin antibodies.

PMID- 9235544
TI  - [The correction of the pathological changes in the neuroendocrine system in
      hyperlipoproteinogenic microangiopathy].
AB  - Thymalin and alpha-tocopherol were studied for their effects on the
      morphofunctional status of the hypothalamopituitary neurosecretory system,
      thyroid, and adrenals in early atherogenesis. Correction of abnormal changes in
      the neuroendocrine organs restored lipid hemostasis, lowered the rate of lipid
      peroxidation, and prevented the progression of atherosclerotic changes in the
      great arteries.

PMID- 9235546
TI  - [Heart lesions in patients with systemic sclerosis].

PMID- 9235545
TI  - V(D)J recombination frequency is affected by the sequence interposed between a
      pair of recombination signals: sequence comparison reveals a putative
      recombinational enhancer element.
AB  - The immunoglobulin heavy chain intron enhancer (Emu) not only stimulates
      transcription but also V(D)J recombination of chromosomally integrated
      recombination substrates. We aimed at reproducing this effect in recombination
      competent cells by transient transfection of extrachromosomal substrates. These
      we prepared by interposing between the recombination signal sequences (RSS) of
      the plasmid pBlueRec various fragments, including Emu, possibly affecting V(D)J
      recombination. Our work shows that sequences inserted between RSS 23 and RSS 12,
      with distances from their proximal ends of 26 and 284 bp respectively, can
      markedly affect the frequency of V(D)J recombination. We report that the entire
      Emu, the Emu core as well as its flanking 5' and 3' matrix associated regions (5'
      and 3' MARs) upregulate V(D)J recombination while the downstream section of the
      3' MAR of Emu does not. Also, prokaryotic sequences markedly suppress V(D)J
      recombination. This confirms previous results obtained with chromosomally
      integrated substrates, except for the finding that the full length 3' MAR of Emu
      stimulates V(D)J recombination in an episomal but not in a chromosomal context.
      The fact that other MARs do not share this activity suggests that the effect is
      no mediated through attachment of the recombination substrate to a nuclear matrix
      associated recombination complex but through cis-activation. The presence of a 26
      bp A-T-rich sequence motif in the 5' and 3' MARs of Emu and in all of the other
      upregulating fragments investigated, leads us to propose that the motif
      represents a novel recombinational enhancer element distinct from those
      constituting the Emu core.

PMID- 9235548
TI  - [The effect of recombinant human erythropoietin (rHu-EPO) on the autonomic
      nervous system in patients hemodialyzed for chronic kidney failure].
AB  - Altered activity of sympathetic nervous system is one of the potential factors
      influencing blood pressure elevation during erythropoietin (rHu-EPO) therapy in
      patients with end-stage renal disease (ESRD). The aim of study was to establish
      if rHu-EPO administration to ESRD patients affects heart rate variability
      (h.r.v.) indices in the time domain and activity of the autonomic nervous system
      (a.n.s.). 23 ESRD hemodialyzed patients were divided into those who recived rHU
      EPO (+EPO), N = 12 and did not receive rHu-EPO (-EPO), N = 11. +EPO patients were
      given 2000-4000 IU rHu-EPO/week for 6 weeks. In both groups h.r.v. indices (mRR,
      SDNN, rMSSD and pNN50) were calculated during dialysis sessions and interdialytic
      period and then were analyzed by Cosinor method. It was shown that: 1) during
      dialysis session there were rhythmic changes in all h.r.v. parameters, which can
      be described by Cosinor formula. 2) all h.r.v. indices wee lower in +EPO group as
      compared with -EPO patients. 3) the differences, although not significant, may
      indicate sympathetic activation in +EPO ESRD patients. 4) Cosinor method applied
      to h.r.v. analysis may be useful tool for assessing a.n.s. activity.

PMID- 9235547
TI  - [Monitoring kidney function in patients with essential hypertension treated with
      enalapril].
AB  - Hypertension may to be both, cause and the results of the renal dysfunction. The
      N-acetyl-glucosaminidase (NAG) is a lysosomal enzyme of renal proximal tubular
      cells. An elevation of the enzyme activity in urine was observed in kidney
      diseases and also in hypertension. The aim of our study was the evaluation of the
      influence of the 6-months-lasting enalapril therapy on function of renal tubules
      and glomeruli in patients with essential hypertension. This study included 30
      patients with essential hypertension (I-II grade according to WHO criteria),
      divided into two groups according to the initial NAG activity in urine: I-with
      normal NAG activity, II-with elevated NAG activity. Enalapril administered in
      doses 2.5-10 mg per day. The urine NAG activity, the urine and serum creatinine
      concentrations, the urea serum concentration and the creatinine clearance were
      determined after 2, 4, 8 weeks, 3 and 6 months of enalapril therapy.
      Simultaneously, the blood pressure and the heart rate were measured and the
      resting ECG was registered. In the course of the 6-months enalapril therapy of
      hypertension, NAG activity in urine in the group II was declined to normal
      values, the creatinine concentration in the urine increased in groups I and II,
      and the blood pressure was significantly reduced. The results of our study imply
      that the monitoring of the NAG activity in urine during the enalapril therapy of
      hypertension, may to be a indicator of protective action of the drug on the
      kidney and its antihypertensive efficacy.

PMID- 9235549
TI  - [Preliminary evaluation of a method for detection of individual malignant
      melanoma cells in peripheral blood while monitoring the course of the malignancy
      and its treatment].
AB  - Using reverse transcription and polymerase chain reaction (PCR) with primers
      specific for tyrosinase the individual melanoma cells were detected in peripheral
      blood of patients in different stages of disease, after excision of primary
      lesion and prior and after chemotherapy. No relation between stage of disease
      (including situations with overt generalized spread of melanoma) and probability
      of positive PCR reaction detecting transcript for tyrosinase gene was found. Many
      patients in III and IV stages were negative for prolonged periods. Therefore,
      this method cannot be used for monitoring of all patients, because many of them
      are negative prior as well as after chemotherapy. With regard to the effects of
      therapy, the patients differed one to another and although some persons positive
      prior treatment became negative thereafter, a similar number of initially
      negative patients became positive after treatment.

PMID- 9235550
TI  - [Lipid risk factors of coronary heart disease during longterm observation of a
      Warsaw Pol-Monica population-based cohort].
AB  - The aim of the study was searching for explanatory variables of high mortality
      from coronary heart disease (CHD) observed in Poland, with special regards to
      lipid risk factors, which were determined in a population of Warsaw Pol-MONICA
      Project. From the randomly selected cohort of Warsaw population, consisted of 348
      men and 351 women, aged 35-64 at baseline, the fasting lipid levels were
      determined three times in 270 men and 266 women. The first study was performed in
      1984 year, second in 1988 and third in 1993. The plasma level of triglycerides
      (TG), total cholesterol (CH) and HDL cholesterol (HDL), after VLDL and LDL
      precipitation, were measured by standardized enzymatic methods. LDL cholesterol
      (LDL) was calculated according to Friedewald's formula. Our laboratory was
      systematically controlled by WHO Lipid Reference Laboratory in Prague and CDC
      NHLBI Lipid Standardization Program in Atlanta. After ten years of following up
      total plasma CH increased significantly by 5% in women (from 5.66 to 5.94 mmol/l
      i.e. 219 to 230 mg/dl) and did not increase significantly in men (increase by 2%,
      from 5.63 to 5.75 mmol/l i.e. 218 to 222 mg/dl. LDL fraction increased
      significantly in both sex groups: by 11% in women (from 3.43 to 3.79 mmol/l i.e.
      133 to 147 mg/dl) and by 9% in men (from 3.42 to 3.73 mmol/l i.e. 132 to 144
      mg/dl). HDL fraction level changed only within the limits of the accuracy of
      method. Plasma TG decreased significantly in both sex groups; by 12% in women
      (from 1.58 to 1.39 mmol/l i.e. 140 to 123 mg/dl) and by 19% in men (from 1.93 to
      1.57 mmol/l i.e. 171 to 139 mg/dl). The significant increase in percentage of
      subjects with elevated atherogenic lipoprotein fraction LDL (LDL >or= 4.1 mmol/l
      i.e. 160 mg/dl) in both gender groups and prevalence of hypercholestrolemia (CH
      >or= 6.5 mmol/l i.e. 250 mg/dl) in women only was observed during ten years.
      Simultaneously the significant decrease in the percentage of subjects with
      elevated level of triglycerides (TG > or = 2.3 mmol/l i.e. 200 mg/dl) in both
      gender groups was noticed. The relationship between lipid risk factors and age
      and relative body mass in all subjects was analyzed. In Polish population the
      levels of lipids and of atherogenic lipoproteins fractions were very high and
      during ten years of follow up almost all lipid risk factors, except TG, showed
      disadventage direction of change.

PMID- 9235551
TI  - [Long-term prophylaxis of thromboembolism and fraxiparin].
AB  - 23 consecutive patients were enrolled in the study, 21 after deep venous
      thrombosis, in 40% complicated by pulmonary embolism, and 2 with mechanical
      prosthetic heart valves with contraindications to oral anticoagulation. All of
      them received fraxiparine s.c. in doses of 7500 U anti-Xa daily, from at least 9
      to 24 months. Fraxiparine was well tolerated. Re-thrombosis or signs of pulmonary
      embolisation as well as bleeding complications have not been observed. Long-term
      subcutaneous administration of fraxiparine is an effective and safe alternative
      for the prophylaxis of thromboembolism in cases with contraindication to oral
      anticoagulation, although the danger of osteoporosis should be considered.

PMID- 9235552
TI  - [Accidental poisoning with silo gas].
AB  - Eight cases of poisoning in workers cleaning silo are presented. Silo gas,
      produced during fermentation of vegetable material, contains very toxic nitrogen
      oxides. In this group three workers died within silo, four patients were
      hospitalized (one of them with acute toxic pulmonary oedema, two with sings of
      pneumonia, one had only transient decrease of consciousness) and recovered
      without detectable sequelae. One patient, in general good condition, refused
      hospitalization and recovered.

PMID- 9235553
TI  - [A case of ascites in the course of acute pancreatitis].
AB  - The case of acute alcoholic pancreatitis, complicated by internal pancreatic
      fistula is being reported. The general patients symptom in initial illness period
      was ascites in peritoneal cavity. Biochemical investigation of ascites has shown
      elevated activity of amylase and protein which is typical for pancreatic ascites.
      The late diagnosis of ascites cause (in 3rd week of the illness) and
      complications decreased efficacy of the treatment used (parenteral nutrition and
      somatostatin). Thus worse the course of the illness.

PMID- 9235554
TI  - [Endoscopic treatment of chronic pancreatitis].

PMID- 9235555
TI  - [Biochemical markers of myocardial damage in myocardial infarction].

PMID- 9235556
TI  - [The influence of heparin on histamine level in plasma during the early reaction
      phase of asthma].
AB  - Heparin, well known anticoagulant, can also modulate inflammatory and immunologic
      processes. Some investigators suggest that heparin inhibits mast cell
      degranulation. Mast cells play very important role in early phase of asthmatic
      reaction, releasing many proinflammatory mediators including histamine. The
      purpose of study was to determine the effect of heparin on early asthmatic
      response and on histamine level in plasma after allergen challenge. Eleven
      patients with mild and moderate asthma were studied in a double blind placebo
      controlled manner. Sodium heparin or placebo were taken via nebulizer, and 15
      minutes later allergen challenge (Dpt./grass pollen) was performed. FEV1 was
      measured at 5, 15, 30 and 60 minutes after challenge and PC20 for allergen was
      calculated. Peripheral blood was collected before and 30 minutes after challenge
      to assess histamine concentration in plasma by an immunoenzymatic assay. We
      observed that heparin significantly decreased early asthmatic response in all
      patients. After challenge with the same concentration of allergen FEV1 fell 36%
      for placebo and 8% for heparin. Heparin also prevented rise in histamine level in
      plasma after allergen challenge. The concentration of histamine before and after
      challenge were respectively 9.55 +/- 4.08 and 13.06 +/- 3.86 nM for placebo (p <
      0.05) and 8.88 +/- 1.50 and 11.18 +/- 1.84 nM for heparin (p > 0.05). There was
      no correlation between FEV1 and histamine level before and after challenge. Our
      results suggest that heparin diminishes allergen induced early phase of asthmatic
      recreation by inhibition of mast cells degranulation.

PMID- 9235558
TI  - [Somatomedins--structure, mechanism of action and clinical significance].

PMID- 9235557
TI  - [Biochemical markers of coronary reperfusion].

PMID- 9235559
TI  - [Lupus nephropathy--therapeutic options 1996].

PMID- 9235560
TI  - [Professor Wladyslaw Tkaczewski--life and achievements of a honorary member of
      the Polish Society of Internal Medicine].

PMID- 9235561
TI  - [Immunologic reactions in infections caused by Helicobacter pylori].
AB  - Helicobacter pylori is recognized as an important cause of chronic antral
      gastritis and peptic ulceration. Moreover, H. pylori associated inflammatory
      process has been linked with gastric carcinoma. Many putative virulence factors
      of H. pylori have been suggested, including motility, urease and cytotoxins
      production and bacterial adhesins. An accessory function of CagA antigen and
      bacterial heat-shock proteins in the pathogenesis of H. pylori infections have
      been also considered. H. pylori-induced immunological response is discussed as
      regards local and general antibody production, the interaction of the bacteria
      with the phagocytes and still controversial involvement of T cells. Data on the
      importance of cytokines and inflammatory mediators in the disruption of the
      gastric mucosal barriers as well as the evidence to support a role for H. pylori
      as a risk factor for gastric carcinoma are also presented.

PMID- 9235562
TI  - [The role of proteolytic enzymes in the pathogenesis of primary
      glomerulonephritis].
AB  - There are many evidences that nonimmunologic factors contribute to pathogenesis
      of primary glomerulonephritides. Proteolytic enzymes plays important role in
      glomerular protein turn-over and their altered activities may have influence on
      glomerular function. The purpose of this paper was to review the role of
      proteolytic enzymes in initiation and progression of idiopathic glomerular
      diseases.

PMID- 9235563
TI  - [The role of Porphyromonas gingivalis proteinases in periodontitis].
AB  - Periodontitis, an inflammation of periodontal tissues, exists in several clinical
      forms. The most common one is adult periodontitis with Porphyromonas gingivalis,
      a Gram-negative anaerobic rod, being generally regarded as the major pathogen
      involved in this disease. This organism produces a large quantity of proteolytic
      enzymes, as virulence factors, which are considered to play a crucial role in its
      pathogenecity. These enzymes are involved in both destruction of periodontal
      tissues and interrupting host-defence mechanisms through the degradation of
      immunoglobulins and complement factors leading eventually to disease progression.

PMID- 9235564
TI  - [The role of DNA polymorphism in the renin-angiotensin system and the
      pathogenesis of cardiovascular diseases].
AB  - Myocardial infarction and stroke are the major cause of death in developed
      countries and are the clinical manifestation of atherosclerosis and hypertension.
      Both the environmental factors and genetic predisposition have an influence on
      the pathogenesis of these diseases. Despite we know lots of environmental risk
      factors and we made important advances in the prevention and treatment of
      mentioned diseases, our knowledge about the pathogenic linkage between genetic
      predisposition and cardiovascular diseases is still very little. Activation of
      the renin-angiotensin system has been proposed as a very important step in the
      pathogenesis of hypertension and atherosclerosis. In spite of vasoconstrictor
      activity, angiotensin II can stimulate migration and proliferation of vascular
      smooth muscle cells, macrophage-foam cells formation, adhesion and aggregation of
      platelets and fibrinolytic system inhibition. Angiotensin convertin enzyme
      inhibitors reduce the development of the atherosclerotic process after vascular
      injury and in hyperlipidemic animals. Blockade of renin-angiotensin system seems
      to be also effective in secondary prevention of myocardial infarction in men. In
      sum, the genetic variations inside the renin-angiotensin system which may affect
      the function of its components might have an influence on genetic predisposition
      to cardiovascular diseases. The paper deals with the current state of knowledge
      on association between polymorphic variations in renin gene, angiotensinogen
      gene, angiotensin converting enzyme gene and AT1 receptor gene and primary
      hypertension, ischaemic heart disease and myocardial infarction.

PMID- 9235565
TI  - [Analysis of aromatic DNA adducts in inhabitants of Upper Silesia].
AB  - Aromatic DNA adducts levels were measured in white blood cells collected from
      three groups of volunteers: occupationally exposed group (cokery workers),
      environmentally exposed group (residents from Silesia), control group
      (inhabitants of Biala Podlaska) using ELISA and 32P-postlabelling methods. The
      highest level of DNA adducts was observed in occupationally exposed group,
      slightly lower in the environmentally exposed group and much lower in the control
      group. Seasonal variations in the adducts levels were found in total white blood
      cells and in lymphocytes showing that the levels of DNA adducts reflect the
      present exposure to genotoxic agents in the air. It was also shown using 32P
      postlabelling with HPLC that not only adducts with polycyclic aromatic
      hydrocarbons were found in human DNA.

PMID- 9235566
TI  - [Metabolic disorders in patients with primary carbohydrate deficient glycoprotein
      syndrome].
AB  - The carbohydrate-deficient glycoprotein syndromes are multisystemic inherited
      diseases with severe nervous system involvement. There is indirect evidence for
      deficiency of phosphomannomutase in type I and direct evidence for a deficiency
      of N-acetylglucosaminyltransferase II in type II. The disease is characterized by
      carbohydrate deficiencies of a number glycoproteins, including serum
      sialotransferrins.

PMID- 9235567
TI  - [L-MTP-PE--a potential antineoplastic agent].
AB  - Muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic lipophilic
      analogue of muramyl dipeptide, stimulates monocytes/macrophages to kill a variety
      of tumor cells in vitro and in vivo. Encapsulation of MTP-PE into multilamellar
      liposomes (L-MTP-PE) was specifically designed for in vivo targeting to
      macrophages by i.v. infusion and is the only form of the drug currently available
      for clinical trials (CGP 19835A Lipid). L-MTP-PE is presently undergoing clinical
      trials in patients with recurrent osteosarcoma and melanoma. L-MTP-PE combined
      with other anticancer agents may thus improve long-term cure rates of patients
      with this diseases.

PMID- 9235568
TI  - [Optimization of measures for prevention and early detection of tuberculosis in
      children and adolescents in the Republic of Sakha].
AB  - The paper analyzes the reasons for the incidence of tuberculosis among children
      in the Republic of Sakha (Yakutia) in the past 5 years. It estimates its growth,
      identifies its sources, risk factors worsening the epidemiological situation.
      Based on the study, the paper gives recommendations how to optimize
      antituberculous measures by taking into account the specific epidemiological and
      socioeconomic situation in the region.

PMID- 9235569
TI  - [Phthisiobacteriological service in the Republic of Sakha].
AB  - The paper shows it expedient to decentralize the bacteriological service system
      by setting up a wide net of laboratory rooms at district antituberculosis
      dispensaries, as shown in the Republic of Sakha (Yakutia). The establishment of a
      branched network of bacteriological rooms and the introduction of procedures of
      centralized preparation of yolk culture media as an intermediate products allowed
      the cohort of tuberculosis and risk groups to be bacteriologically studied to a
      greater extent.

PMID- 9235570
TI  - [Analysis of active tuberculosis morbidity of children from follow-up group VIA].
AB  - The follow-up and drug prophylaxis of 30 children who had been registered for a
      turn of tuberculin tests in 1993-1995 and subsequently ill with tuberculosis were
      analyzed. Among the causes of the disease there was a combination of 2 risk
      factors or more (epidemiological, age- and sex-specific, biomedical, clinical,
      genealogical, social), uncontrolled and ineffective drug prophylaxis, inadequate
      X-ray study in early tuberculous infection.

PMID- 9235571
TI  - [Duration of treatment and followup of patients operated for peripheral lymph
      nodes tuberculosis].
AB  - The paper analyzes patients with localized caseous necrotic tuberculosis of the
      peripheral lymph nodes, who were treated with antituberculous agents and
      underwent early surgical interventions. Follow-ups of the patients' status,
      changes in the clinical signs of the disease, hemograms, ESR, and immunological
      parameters revealed that the duration of the basic treatment regimen and follow
      ups averaged 5 months and 4 years, respectively.

PMID- 9235572
TI  - [Treatment of tuberculosis patients with massive bacterial excretion].
AB  - A new endobronchial treatment has been developed for patients with destructive
      pulmonary tuberculosis with massive bacterial excretion, complicated by chronic
      nonspecific endobronchitis. The treatment includes inhalation therapy with
      antituberculous drugs dissolved in activated silver water. This treatment of 42
      patients has shown more than 2-fold increases in the rate of massive bacterial
      excretion cessation.

PMID- 9235573
TI  - [X-ray study in pediatric phthisiology++ ].
AB  - The number and regularity of X-ray studies in adolescents with active chest
      tuberculosis in the Republic of Sakha (Yakutia) were analyzed. There was a high
      proportion of early X-ray examinations. The larger number (more than 80%) of X
      ray studies were conducted for follow-ups of a specific process. In this
      connection, radiation load on adolescents from the examined groups was several
      times higher than the mean radiation dose for the population during X-ray
      examinations.

PMID- 9235574
TI  - [Tuberculosis in Iakutia: problems and ways of their solution].

PMID- 9235575
TI  - [Use of external laser radiation in patients with infiltrative pulmonary
      tuberculosis].
AB  - A procedure has been developed for the use of semiconductor laser radiation in
      the combined drug therapy of patients with disseminated infiltrative pulmonary
      tuberculosis with multiple destructions and massive bacterial excretion, by
      increasing the number of sessions, which reduces the time of bacterial excretion
      cessation by 2-4 weeks, decay cavity closure by a months, and hospital treatment
      by 1.5 months and promotes minimal residual changes in most of them.

PMID- 9235576
TI  - [Clinical features of tuberculosis in adolescents in Iakutia].
AB  - In the past 3 years, there has been an increasing trend of tuberculosis morbidity
      among adolescents in the Republic of Sakha (Yakutia). Moreover, the pattern of
      clinical types has become worse, disseminated and complicated tuberculoses have
      been more frequently detected. There is a predominance of infiltrative pulmonary
      tuberculosis occurring mainly in the intact lung with its asymptomatic onset and
      aptness to lung tissue decay and bacterial excretion.

PMID- 9235578
TI  - [Clinical and bacteriological features of intestinal dysbacteriosis in patients
      with pulmonary tuberculosis].
AB  - In patients with pulmonary tuberculosis, intestinal dysbacteriosis has clinical
      and bacteriological features characterized by the short-age of bifidobacteria (in
      88-92%), by changes in the composition of Escherichia coli strains (in 38-42%),
      by the presence of Candida (in 58-62%), Proteus in half the patients, and by
      associated dysbacteriosis. Most (75%) patients show Stage III-IV intestinal
      dysbiosis formed after 3-4 months of continuous chemotherapy. There is a direct
      relationship between the magnitude of dysbiotic disorders and the duration of
      chemotherapy.

PMID- 9235577
TI  - [Specific features of tuberculosis in the similar biogeochemical subareas of the
      biosphere in the Chuvash and Sakha (Iakutia) republics].
AB  - The use of biogeochemical zoning of the territories of the Chuvash and Sakha
      (Yakutia) Republics revealed that due to silicon deficiency in the food
      biogeochemical chain, the indigenous population had reduced cellular immunity,
      accumulated residual tuberculous changes leading to higher morbidity, disease
      aggravation, more frequent complications, high tuberculosis mortality.

PMID- 9235579
TI  - [Tuberculosis of peripheral lymph nodes in Iakutia].

PMID- 9235580
TI  - [Features of development, clinical picture and surgical treatment policy of
      destructive forms of pulmonary tuberculosis in the North].
AB  - In 135 patients, follow-up clinical, X-ray, immunological, and pathomorphological
      studies revealed that destructive changes in the form took place as an extensive
      specific process involving more than one lobe with bronchogenic dissemination
      and, commonly, as caseous pneumonia. Despite the extensive destructive changes, a
      tuberculous process is torpid, by showing mild clinical manifestations of the
      onset of the disease. Early lung tissue fibroplastic changes lead to an
      irreversible process after 4-5 months of antibiotic therapy, which suggests
      failure to cure them and makes it necessary to apply surgical treatments.

PMID- 9235581
TI  - [Immune responsive features in patients with pulmonary tuberculosis complicated
      by intestinal dysbacteriosis].
AB  - Clinical and immunological studies made in 130 patients with various types of
      pulmonary tuberculosis ascertain that the absolute majority (90%) patients who
      begin to develop intestinal dysbacteriosis due to long-term chemotherapy have T
      cell immunity impairments, which appears as their quantitative shortage and
      functional insufficiency. There is a marked decrease in T helper levels with
      subpopulation imbalance and lower Tx/Tc ratios. The applied complex of corrective
      means produces stimulating and correcting effects on cellular and humoral
      immunological responses, promotes the increase of T helper counts, by eliminating
      the imbalance of regulatory subpopulations of T lymphocytes and having a
      beneficial effect on the clinical and X-ray changes in pulmonary tuberculosis.

PMID- 9235582
TI  - [Changes and patterns of drug resistance of mycobacterium tuberculosis in
      patients with pulmonary tuberculosis (by data of the microbiological laboratory
      of research production association "Phthysiology")].
AB  - Changes in and patterns of drug resistance of Mycobacterium tuberculosis were
      analyzed in Yakutia. It was shown that in the past 5 years, there had been no
      rise in the total resistance; however, its patterns changed: a proportion of
      polyresistant strains had increased with decreases in monoresistant strains. The
      rate of Mycobacterium tuberculosis resistance to most antituberculous drugs was
      found to be growing. The pattern of resistance is varying in different areas of
      Yakutia.

PMID- 9235583
TI  - [Levels of trace elements in lung tissue of patients with tuberculosis in
      Iakutia].
AB  - The study was first undertaken to examine the levels of trace elements in the
      resected portions of the lungs from 33 patients and 8 healthy individuals who had
      died from injuries, by using the quantitative spectral analysis. The trace
      element spectrum in the lung tissue was found both in the patients and healthy
      persons. Ratios of the concentrations of some vital trace elements were
      determined in healthy individuals and patients with various types of
      tuberculosis. There was a direct relationship between the levels of trace
      elements and the severity of a pathological process. A change in their
      concentrations is likely to be associated with weather factors, biogeochemical
      features of the region.

PMID- 9235584
TI  - [Pulmonary tuberculoma in the North: pathomorphological study].
AB  - Autoptic specimens from tuberculosis patients operated on, delivered to the
      Laboratory of Pathomorphology, Institute of Tuberculosis, were used to examine
      quantitative changes, age-sex ratio, ethnicity, and admission of patients with
      pulmonary tuberculoma by climatic and geographical regions of Yakutia. The
      morphological types of tuberculomas, their numbers, size, activation, ratios by
      ethnicity were identified. Their clinical and morphological features were
      determined both by climatic and geographical conditions and the quality and
      nature of treatment, the distinguishing features of a contingent of patients. The
      pattern of the more severe process in the indigenous population calls for close
      attention and further study.

PMID- 9235585
TI  - [Effectiveness of collapse surgical interventions in patients with destructive
      pulmonary tuberculosis].

PMID- 9235586
TI  - [Thoracoplasty in pulmonary tuberculosis].

PMID- 9235587
TI  - [Time course of changes in tuberculosis epidemiological parameters in Iakutia
      over 12 years (1983-1994)].
AB  - In the past 12 years, there were 1.3- and 1.9-fold reductions in the total
      morbidity rates of tuberculosis and its spread, respectively. However, its
      morbidity among children showed 3-fold increases. The reduction rate of bacterial
      excretion became much slower in the past 4 years. Tuberculosis mortality rates
      tended to rise. At the moment of study, the basic tuberculosis epidemiological
      parameters were 1.3-1.5 times higher than those in the Russian Federation. At the
      same time there was a decrease in the efficiency of antituberculous work at all
      levels.

PMID- 9235588
TI  - [From the history of the antituberculosis service in Iakutia (to the 70th
      anniversary of the antituberculosis service in Iakutia)].

PMID- 9235589
TI  - [Basic developmental stages of tuberculosis science in Iakutia].

PMID- 9235590
TI  - [Significance of activities of a medical sanitary detachment from complex
      expedition if the USSR Academy of Sciences (1925-1930) in the development of
      surgical treatment for osteoarticular tuberculosis in Iakutiia].
AB  - The paper shows the value of the activities of a medical sanitary detachment from
      the complex expedition of the USSR Academy of Sciences (1925-1930) in the
      development of surgical treatment for bone and joint tuberculosis and its
      sequelae in adults from Yakutia. A total of 981 operations were made from 1951 to
      1994. Priorities were given to timely surgical interventions, including radical
      reparative spinal and joint operations, by using the Ilizarov apparatus.

PMID- 9235591
TI  - [Changes of isoniazid concentrations in guinea pig blood and organs after various
      routes of drug administration].
AB  - Isoniazid concentrations were measured in the serum, liver, and lungs of the
      animals 1, 3, 6, and 24 hours after administration of isoniazid in a dose of 10
      mg/kg via various routes (orally, intramuscularly, and lymphotropically--into the
      pretracheal cellular space) guinea-pig blood and organs in the experiment on 36
      guinea-pigs. Within the first 1-3 hours after intramuscular injection of
      isoniazid, its concentrations in the serum and lungs were higher than those with
      other routes of administration. With lymphotropic and oral routes, the levels of
      the drug were very similar in all the studied media in the first 6 hours, but
      later its hepatic accumulation after lymphotropic administration proved to be
      considerably lower than via other routes. The lymphotropic injection of isoniazid
      provides its therapeutic concentrations in the blood and in the lung and
      simultaneously creates prerequisites for reducing the incidence and severity of
      hepatotoxic adverse reactions.

PMID- 9235592
TI  - [Luminol-dependent neutrophilic chemiluminescence in patients with chronic
      nonspecific lung diseases].
AB  - To assess the prognostic value of neutrophilic chemiluminescence, an examination
      was made of 68 patients with chronic bronchitis, 96 with bronchial asthma, and 34
      apparently healthy individuals. Metabolic activity was determined by spontaneous
      and induced chemiluminescence in the whole blood and neutrophilic samples (the
      procedure being given). Patients with chronic bronchitis or bronchial asthma were
      found to have much higher metabolic activity in the neutrophils. The high
      sensitivity of chemiluminescence enables it to be used to determine the natural
      history of a disease and to check up the efficiency of treatment.

PMID- 9235593
TI  - [Characterization of various types of mycobacterium tuberculosis cultured on
      their unusual host].
AB  - The authors examined the adaptive variability of pathogens of human and avian
      tuberculosis, consequently passaged on calves 4 times, that of human and bovine
      tuberculosis, consequently passaged on chickens 8 times, and Mycobacteria of
      avian tuberculosis, consequently passaged on guinea-pigs 8 times. Due to
      consequent passages of Mycobacteria tuberculosis on their uncommon host, they
      were found to acquire properties species-specific to the animal through whose
      body they had been passaged.

PMID- 9235594
TI  - [Recurrence of pulmonary tuberculosis in adults in the areas of the Republic of
      Sakha (Iakutia)].
AB  - The dynamics in recurrences of pulmonary tuberculosis was analyzed in the areas
      of Yakutia. The social and clinical characteristics of patients with recurrences
      and their treatment outcomes are presented in the paper. Recurrences of pulmonary
      tuberculosis were found to occur more frequently in the areas having a poor
      epidemiological tuberculosis situation and among socially unprotected groups of
      the population. Under these conditions, recurrences may occur in 30 years or more
      after clinical cure of tuberculosis. To treat patients with recurrences in the
      area presents great difficulties.

PMID- 9235595
TI  - Morphological reactions in the subcutaneous fat after lymphotropic administration
      of isoniazid: experimental study.
AB  - Two experiments were conducted on 36 guinea-pigs. One of them examined the
      morphology of the distribution of the intravital stain trypan black with
      isoniazid 1, 3, 6, 24, and 48 hours after their administration into the
      subcutaneous fat of the neck and axilla. It demonstrated that the agents came
      from the subcutaneous fat largely to the intrathoracic lymph nodes and lungs via
      the lymphatics in a retrograde way. The other experiment on 16 healthy guinea
      pigs indicated that 1, 2, and 3 months after lymphotropic administration (into
      the pretrachea and axilla), an infiltrate appeared and increased at the site of
      drug administration, which became larger after 3 months of lymphotropic
      injection, and after discontinuation it is completely resolved and the tissue
      structures of the subcutaneous fat recovered.

PMID- 9235596
TI  - [Antibacterial effectiveness of long-acting isoniazid in the experiment].
AB  - The therapeutical efficiency of the long-acting lysosomotropic, complex drug
      isoniazid (LALCI) was tested in vivo and its antibacterial activity was studied
      in vitro. LALCI treatment of mice inoculated by virulent Mycobacterium
      tuberculosis was found to increase their life by 33% as compared with isoniazid.
      The findings suggest that the higher antibacterial effect of LALCI was due to the
      dextran matrix that potentiates the antibacterial activity of macrophages by
      acting on phagosomal and lysosomal cohesion.

PMID- 9235597
TI  - [Rating control in the working program on phthisiology].

PMID- 9235598
TI  - [Psychological and moral aspects of physician's training at the
      phthisiopulmonological clinic of medical university].

PMID- 9235599
TI  - [Phthisiologist's qualification certification by using tests and personal
      computers].

PMID- 9235600
TI  - [The plenary Meeting of the Research Medical Association of Phthisiologists and
      the Research and Practical Conference af the Mari Republican Center for
      Tuberculosis Control].

PMID- 9235601
TI  - [Significance of expedition studies in epidemiology of tuberculosis in Iakutia
      (to 70 anniversary of the first expedition)].
AB  - The paper gives the data of expedition studies made since 1925 by the USSR
      Academy of Sciences, the USSR Academy of Medical Sciences, the USSR and RSFSR
      Peoples' Commissariat of Health, to examine to the epidemiology of tuberculosis
      in Yakutia, whose significance is very great in combatting tuberculosis and
      setting up the antituberculosis service in the republic. Over 70 years since the
      first complex expedition made by the USSR Academy of Sciences there has a more
      than 55-fold reduction in the spread of tuberculosis in the Republic of Sakha
      (Yakutia).

PMID- 9235602
TI  - The electronic Plant Gene Register.

PMID- 9235604
TI  - [Human and technical resources of arrhythmia units in Spain in 1995].
AB  - The results of the Spanish registry for electrophysiology and arrhythmias
      activity are presented. A questionnaire was sent to all of the Arrhythmia Units
      in Spain, directed to their human and technical resources, and activity. The
      questionnaire was designed by the Section of electrophysiology and Arrhythmias of
      the Spanish. Society of Cardiology. The existence of an arrhythmia Unit, as an
      autonomous center, was recognized in 26 cases, at the end of 1995. In 13 centers
      there was no Arrhythmia Unit, but 11 wanted to develop one and in 2 it was not
      considered. Seven centers expected to create an Arrhythmia Unit during 1996. The
      first Arrhythmia Unit in spain was created in 1979. We have considered as a basic
      requirement the functional existence of a specific cardiac electrophysiological
      laboratory. Only 34 hospitals already have a Laboratory and 5 are waiting for the
      development of one. In 21 hospitals there are cardiologists particularly
      dedicated to electrophysiology, the number varies between 1 and 3 in each
      hospital. Radiofrequency catheter ablation is now considered the technique of
      choice for the treatment of most cardiac arrhythmias. This technique is currently
      being performed in Spain in 29 Hospitals and an additional 4 are expected to be
      able to perform it in the near future. Twenty-five hospitals implant automatic
      defibrillators, and the mean defibrillators implanted per hospital and year is
      9.8 +/- 10.1.

PMID- 9235603
TI  - [Current status of arterial hypertension as a cardiology topic: point of view of
      the cardiologist. Task force on Arterial Hypertension of the Spanish Cardiology
      Society].
AB  - Even if arterial hypertension (HT) is a process of multiorganic involvement, it
      is nevertheless in practice, one of the most powerful factors for the development
      of cardiovascular complications that increases very seriously, both
      cardiovascular morbidity and mortality. Paradoxically, in Spain, a significant
      proportion of cardiologists have neglected for many years this disease, at least,
      at its initial phase, acting mainly, only when the usual and severe
      cardiovascular complications of HT were clinically well established. Currently,
      this attitude is changing in such a way, that in the near future, the
      cardiologist's commitment to HT, will be definitely engaged in both; basic
      research and clinical aspects. The Spanish Hypertension Working Group, has worked
      out in an inquiry sent to all Spanish cardiologists, in order to know their point
      of view in relation to the main aspects involving HT and cardiological practice.
      This paper collects the results of the answers given anonymously by the doctors.

PMID- 9235605
TI  - [Diastolic dysfunction, left ventricular hypertrophy, and microalbuminuria in
      mild to moderate essential arterial hypertension].
AB  - INTRODUCTION: It is known, that there is a high prevalence of left ventricular
      diastolic disfunction, which precedes left ventricular hypertrophy in
      hypertensive people, but there is little published in literature about the
      relationship between these findings and the presence of microalbuminuria.
      OBJECTIVE: In our study, we pretend to evaluate prevalence and eventual relation
      among microalbuminuria, diastolic disfunction and left ventricular hypertrophy,
      in young mild to moderate hypertensive patients, non diabetic and without
      previous treatment. MATERIAL AND METHODS: We studied prospectively 80 untreated
      hypertensive patients, with normal serum creatinine, and non diabetic (52.5%
      women and 47.5% men, mean age 41.4 +/- 9.6 years). We evaluated filling indexes
      by Doppler Echocardiography: Ratio of early to late diastolic peak filling
      velocity and early filling deceleration time. Left ventricular hypertrophy was
      defined by Devereux's criteria. Microalbuminuria in twenty four hours was
      measured by radioimmunoassay in hypertensive patients (microalbuminuria: 30-300
      mg/24 hours). RESULTS: Microalbuminuria occurred in 23.7%, left ventricular
      hypertrophy 40%, and diastolic disfunction 48.8%, no significant correlation
      existed between the same. Only 29.5% had no cardiac or renal disease.
      Statistically significant differences were found in ratio of early to late
      diastolic peak filling velocity and microalbuminuria, between the two study
      populations, but multiple regression analysis didn't prove such correlation.
      Ratio of early to late diastolic peak filling velocity was independently related
      to age and diastolic blood pressure. CONCLUSIONS: There is a high prevalence of
      cardiac and/or renal disease in mild hypertensive patients, only 29.5% of these
      patients are free of disease. We don't find relation between lesions in these
      organs.

PMID- 9235606
TI  - [Radiofrequency catheter ablation for atrial tachycardia].
AB  - INTRODUCTION: Radiofrequency catheter ablation of atrial tachycardia guided by
      bipolar activation mapping has been reported in the last years. This article
      reports the use of radiofrequency catheter ablation for the treatment of atrial
      tachycardia using simultaneous bipolar and unipolar activation mapping at our
      institution. METHODS: Nine patients (7 male and 2 female, mean age 37.2 +/- 24.1
      years), were selected for radiofrequency catheter ablation of drug refractory
      atrial tachycardia. Mapping procedure included an investigation of the local
      earliest bipolar and unipolar activity and unipolar morphology analysis. RESULTS:
      Atrial tachycardia was successfully ablated in 7 patients (78%) with an average
      number of 6.8 +/- 3.1 RF pulses. Procedure related complications and tachycardia
      follow-up recurrences were not observed in any patient. Bipolar local activation
      time was significantly shorter at successful than at unsuccessful ablation sites
      (-30 +/- 21.1 ms vs -18.3 +/- 20.6 ms; p = 0.01). No difference was observed in
      unipolar local activation time between successful and unsuccessful sites (-22.5
      +/- 26.2 ms vs -19.8 +/- 21.5 ms; p = 0.56). Accurate localization of the
      successful ablation site by unipolar electrogram analysis was not feasible
      because a "QS" pattern was found at both 21 unsuccessful and 2 successful
      ablation sites. Finally, a fast slope of the negative deflection of the unipolar
      electrogram was found at 2 out of 45 unsuccessful and 3 out of 6 successful
      ablation sites. CONCLUSIONS: Radiofrequency catheter ablation of atrial
      tachycardia is feasible without complications in most patients. Bipolar
      activation mapping accurately localizes the successful ablation site. A "QS"
      pattern is not predictive of successful radiofrequency application.

PMID- 9235607
TI  - [Intracoronary stent in primary angioplasty in acute myocardial infarction].
AB  - INTRODUCTION AND OBJECTIVES: Stent implantation has been generally
      contraindicated during primary percutaneous transluminal balloon angioplasty in
      AMI, because of its possible trombogenicity. Report the early outcome of patients
      undergoing coronary stenting during primary PTCA. METHODS: From january 1995 to
      april 1996, 31 patients underwent stent implantation in primary. Mean age 62 +/-
      11 years. Infarct location was anterior in 20 (65%), and inferior in 11 patients
      (35%). Four patients were in Killip class IV. Mean onset of chest pain was 129 +/
      29 minutes. Indications for stenting were suboptimal result (64%), dissection
      (29%) and elective (6%). All patients were treated with heparin during 72 hours
      and antiplatelet therapy with ticlopidine and aspirin. RESULTS: Coronary stenting
      restored vessel patency with TIMI 3 flow in 29 patients (94%) and TIMI 2 flow in
      2 patients. Angiographic control was performed in 80% of the patients: no stent
      occlusion was observed and all patients showed a TIMI 3 flow. There were 3 deaths
      (9%): 2 patients died due to cardiogenic shock and 1 to severe right ventricular
      dysfunction. 2 patients (6%) had recurrent angina, due to other artery. One
      patient with left main coronary disease underwent elective coronary artery bypass
      graft surgery. CONCLUSIONS: Intracoronary stent can be used successfully during
      primary angioplasty with a low incidence of complications. The long term benefits
      remains to be established.

PMID- 9235608
TI  - [10-day clinical course of a stunned myocardium model with very short and
      repeated ischemias].
AB  - INTRODUCTION AND OBJECTIVES: In previous studies we have observed ischemic
      processes of very brief duration (2 minutes) and with brief reperfusion (3
      minutes), which have been repeated 20 times (ischemic protocol [IP]). They are
      capable of producing contractile dysfunction of the ischemic zone, with a
      decrease of 28.6% at 24 hours, and coronary blood flow maintenance (stunning).
      METHODS: The aim of this study is to examine the evolution of this dysfunction.
      The IP designed in our laboratory was used on 24 adult mongrel dogs. We measured
      regional myocardial function using a pair of implanted chronic ultrasonic
      crystals in the ischemic area (depending on the left anterior descending coronary
      artery) and a second pair in the control zone (depending on the left circumflex
      coronary artery). RESULTS: After analyzing results, we found that the shortening
      fraction decreased to 28.6% (p < 0.05) in 24 hours. During the subsequent five
      days the shortening fraction decreased to a minimum of 67.88% (p < 0.01), after
      which there was a progressive recovery that reached 18.95% (NS) below the base
      line on the tenth day. We did not observe any significant variation in the
      hemodynamic parameters at any time. CONCLUSIONS: The repeated, very brief
      episodes of ischemia (in the experimental terms that we have explained) produced
      a contractile dysfunction which reached its maximum on the fifth day, and
      returned to normal on the tenth day. We hypothesize that these alterations could
      explain the episodes of left ventricular failure with spontaneous recuperation
      observed in stable myocardial ischemia, and for which no immediate cause has been
      found.

PMID- 9235609
TI  - [Progressive postischemic dysfunction: stunning, preconditioning, hibernation,
      and confusion].

PMID- 9235610
TI  - [Surgical treatment of Fallot's tetralogy with hyperplasia or agenesis of the
      conal septum].
AB  - INTRODUCTION: The clinical evolution, anatomosurgical aspects, and postoperative
      evolution of a specific group of Fallot's tetralogy with hipoplasic or agenesic
      of the conal septum (representing a 7% of our Fallot's tetralogy cases) is
      presented. METHODS: A total of 41 patients surgically corrected in our Service
      between February 1973 and December 1995 has been retrospectively studied. Ages
      ranged between 13 months and 13 year. Clinically all cases developed moderate or
      severe hypoxemia. In 43.9% of cases it was necessary to perform a palliative
      surgery at an age between 15 days and 4 years. RESULTS: There was no hypoxemics
      spells. In the ECG we have found a QS in the aVR in 40% of cases. There was 7
      deaths (17% of mortality rate). Four cases required reoperation. The clinical
      evolution, ECG, EKO, and hemodynamics findings are commented. CONCLUSIONS: In
      this type of Fallot's tetralogy, specifically in those cases with a pulmonary
      artery ring of normal size, it is necessary to have a good preoperative diagnoses
      in order to perform a longitudinal ventriculotomy with right ventricular outflow
      tract enlargement. Also, it is important to be meticulous with the stitches in
      the closure of the ventricular septal defect with a patch in order to avoid the
      potential lesion of the aortic valve.

PMID- 9235611
TI  - [Research methods in clinical cardiology (VII). Experimental studies in
      cardiology].
AB  - Experimental designs in clinical investigation are discussed in this article.
      Guideline examples have been used in the area of Cardiology using always the same
      one only one whenever possible. We have looked for a different perspective from
      what is generally used in the discussion of the general characteristics of
      experimental designs, and more specifically of clinical trials and we deal with
      the aspects of clinical trials which are usually ignored due to their marginal
      character. We also discuss those characteristics which differentiate clinical
      trials in respect to other designs and types of questions which are answered by
      clinical trials. And we finally discuss various aspects such as randomization and
      its various types (simple, block, stratified, pre-randomized) and variable types
      of evaluating the answers, masking and the problems in its maintenance, with
      certain kinds of designs, sample size, etc. There is a brief mention of two
      particular cases: factorial and cross over designs are both discussed, mentioning
      their strong and weak points. Likewise, we discuss community trials as another
      experimental design and examples are provided. Finally, we discuss aspects of
      criteria: such as, When to stop the trials? or Who are the results applicable
      to?, and we suggest points to take into consideration when these decisions are
      made.

PMID- 9235612
TI  - [Exercise-induced atrioventricular block. Significance of the ischemic component.
      Report of 4 new cases].
AB  - We report four new cases of exercise-induced atrio-ventricular block (appearing
      during treadmill exercise testing). The mechanism was ischemia in two patients
      and the conduction disturbance disappeared after coronary artery bypass grafting.
      The literature on this matter is reviewed. Also the etiology, the natural history
      and management are discussed in these cases.

PMID- 9235613
TI  - [Usefulness of transesophageal echocardiography in the detection of embolic risk
      in a case of Staphylococcus aureus endocarditis].
AB  - Embolism is very frequently found in patients with infective endocarditis (IE),
      fundamentally in cerebral arteries. An early diagnosis and possible complications
      seem to be related to morbidity and mortality. Echocardiography has a
      considerable function in early diagnosis, and, also, when we evaluate the risk of
      major cerebral embolism. However there is no agreement in the second aspect: for
      some authors echocardiography only slightly aids, but others consider it of great
      value in identifying high-risk patients. We describe a patient who suffers
      infective endocarditis by Staphylococcus aureus with significant neurological
      complications in its evaluation. Vegetation was disclosed by transesophageal
      echocardiography (TEE), whereas transthoracic echocardiography (TTE) was unable
      to do so. This is why we underline the role of TEE in the diagnosis and
      description of vegetation features (size, mobility and implantation) which seem
      to be linked to the risk of cerebral complications.

PMID- 9235614
TI  - [Asymptomatic aortic dissection in a patient with aortic valve prosthesis].
AB  - The occurrence of iatrogenic aortic dissection after aortic valve replacement is
      uncommon, usually late, and exceptionally asymptomatic. We present here a case of
      dissecting aneurysm suspected by excessive mediastinal dilatation observed in the
      routine annual roentgenogram exam of a patient who has had an aortic valve
      prosthesis for thirteen years. The confirmation with other diagnostic methods and
      its successful surgical treatment are also described.

PMID- 9235615
TI  - [Cor triatriatum with interventricular communication: Doppler color
      ultrasonography and magnetic resonance diagnosis. Repair in the first months].
AB  - We report a case of left cor-triatrial with ventricular septal defect and patent
      ductus arteriosus in a lactant of six months of age. It was diagnosed using color
      coded Doppler echocardiography and magnetic resonance imaging. The intracardiac
      defects were successfully corrected through right atriotomy.

PMID- 9235616
TI  - [Chylopericardium following acute pericarditis].

PMID- 9235617
TI  - [Disorders of anticoagulation and fibrinolysis in monoclonal gammopathies-
      another mechanism of paraprotein interference with hemostasis].
AB  - We have investigated the possible interaction of paraprotein (pp) with
      anticoagulation mechanisms and fibrinolysis. Eighty four patients with monoclonal
      gammapathy (MG) were included to the study, 59 of them with multiple myeloma
      (MM). In 48.8% cases some defect was found. Decreased levels of antithrombin III
      (AT III) was observed in 13.3%, protein C (PC) in 18.3% and protein S (PS) in
      13.5% of patients. Distribution between the free and the bound PS fraction
      remained normal. The most frequent abnormality found was the reduction of
      plasminogen (PLG) activity, which was observed in 35.1% and elevated levels of
      plasminogen activator inhibitor, detected in 42.3% of cases, respectively.
      Decreased plasminogen activator activity was observed in only one patient. The
      relationship between isotype and concentration of paraprotein and frequency of
      factor levels abnormalities was not found. The incidence of arterial and/or
      venous thrombosis was higher in patients with laboratory defect in comparison
      with the unaffected, however, the difference was not statistically significant.
      In contrast, the incidence of hemorrhagic complications was significantly lower
      in these patients (p < 0.01), although in most of them simultaneous defect of
      plasmatic coagulation and/or platelet functions was detected. We suggest, the
      interaction with both hemostatic and anticoagulation systems could result to
      "elimination" of inauspicious effect of pp on hemostasis. The impairment of
      anticoagulation systems and fibrinolysis is another type of paraprotein
      interference with hemostasis. It is also considered to be another pathogenetic
      mechanism of secondary deficiency of AT III, PC, PS and PLG.

PMID- 9235618
TI  - [Antiphospholipid antibodies in patients with neurologic diseases].
AB  - In a series of patients with neuroinfection, Lyme disease, Guillain Barre
      syndrome, demyelinization, partial or generalized, epilepsy, we have investigated
      antiphospholipid antibodies of IgG and IgM subtypes, together with anticoagulant
      factors, member of thrombocytes, sedimentation rate of erythrocytes. Coagulant
      factor disorder in primary acute inflammatory processes (attack of
      demyelinization, neuroinfection, acute viral respiratory infection) and primary
      thrombocyte disorder (focal epilepsies) may be a result of cross reaction of
      antiphospholipid antibodies with negative polarized phospholipids in membranes of
      central nervous system, endothelium of cerebral and extracranial vessels and in
      the inner thrombocyte membranes connected with prostaglandin production disorder.

PMID- 9235619
TI  - [Acute mesenteric occlusion (analysis of 4 cases)].
AB  - Sudden, complete occlusion of the superior mesenteric artery is due often to an
      embolus than thrombosis. The clinical features are usually the same whether
      occlusion is the result of embolism or thrombosis. Males are affected more often.
      Complete thrombotic or embolic occlusion of the mesenteric artery presents mostly
      as a surgical emergency with all the manifestations of paralysis of the
      peristaltic mechanism as well as loss of viability of the affected intestine.
      There are problems in the diagnosis in, the group of higher age patients. The
      clinical diagnosis is by patients with minimal symptomatology and often with next
      diseases very complicated and unfortunately to late. The authors described four
      examples of this problematic.

PMID- 9235620
TI  - [Results of surgical treatment of pancreatic carcinoma].
AB  - Experiences in pancreatic surgery revealed substantial mortality decrease in
      pancreatic resections and these procedure became treatment of the first choice
      for resectable pancreatic tumors in last ten years. Our results support this
      experience, we performed pancreatic resections in 51% of 155 patients we operated
      on in last five years, with mortality rate not exceeding 5%. Morbidity of
      pancreatic resections remains low in comparison with palliative procedures and
      resections provide better quality of life even in advanced disease. Together with
      adjuvant chemotherapy there is a possibility to offer an acceptable treatment for
      pancreatic tumors.

PMID- 9235621
TI  - [Experiments of Dr. Vincenc Strouhal at the Klementine Radiologic Facility in
      Prague].

PMID- 9235622
TI  - [We are finally repaying our debt (F.C. Opitz, 1810-1866)].

PMID- 9235624
TI  - Proceedings of the 3rd International Workshop of the International Enuresis
      Research Center. Aarhus, Denmark, 18-20 October 1996.

PMID- 9235623
TI  - [Jan Jessenius (1566-1621)].

PMID- 9235625
TI  - Raiders of the last bastion?

PMID- 9235626
TI  - Allegations prompt debate in Germany.

PMID- 9235627
TI  - Resurgent mosquitoes, dengue in Cuba.

PMID- 9235628
TI  - DNA from an extinct human.

PMID- 9235629
TI  - Amino acid alchemy transmutes sheets to coils.

PMID- 9235630
TI  - Newfound gene holds key to cell's cholesterol traffic.

PMID- 9235631
TI  - One molecule orchestrates amoebae.

PMID- 9235632
TI  - The space around us.

PMID- 9235633
TI  - The transcriptional paradox: octamer factors and B and T cells.

PMID- 9235634
TI  - John C. Eccles (1903-1997).

PMID- 9235636
TI  - Guidelines for the surgical practice of telemedicine. Board of Governors of the
      Society of American Gastrointestinal Endoscopic Surgeons.

PMID- 9235635
TI  - Ethical and policy issues of human cloning.

PMID- 9235637
TI  - [Radiotherapy in the multimodal treatment of esophageal carcinoma. A review].
AB  - BACKGROUND: The curative potential of exclusively applied surgery or radiotherapy
      on esophageal carcinoma is exhausted. The 5-year survival rate of surgically
      treated esophageal carcinoma is stagnant at 20 to 30%, that for
      radiotherapeutically treated esophageal carcinoma at < or = 10%. The unchanged
      bad prognoses motivate the search for multimodal therapeutical concepts in order
      to improve the results of basic therapies. METHOD, RESULTS AND CONCLUSIONS: While
      neither perioperative radiotherapy nor perioperative chemotherapy were able to
      improve the treatment results significantly, a progress in the field of primary
      and preoperative radiochemotherapy emerges. On locally restricted tumors the
      latest findings show that a simultaneous radiochemotherapy with Cisplatin is more
      effective than radiotherapy alone. 20 to 30% histologically verified complete
      remissions can be reached through preoperative radiochemotherapy. These results
      will influence future treatment concepts. Brachytherapy can be taken into
      consideration in highly palliative situations as exclusive method of treatment or
      for support of laser treatment or bouginage for removal of stenosis. As the
      number of clinically controlled studies is not sufficient the importance of the
      brachytherapy boost for potentially curative intentions is not yet clear. Up to
      now the intraluminal hyperthermia is a underestimated method for improving the
      results of radiotherapy. Our overview summarizes all presently published
      randomized studies and relevant phase I/II-studies.

PMID- 9235638
TI  - [Radiotherapy after radical prostatectomy: indications, results and side
      effects].
AB  - BACKGROUND: Radiation therapy following radical prostatectomy in locally
      progressed prostate carcinoma has become increasingly important in the last few
      years as both adjuvant therapy in patients with pT3-tumors with or without
      positive margins and treatment for a PSA increase in local recurrence of disease.
      The background for this is the knowledge gained by using PSA that up to 60% of
      the patients with histopathologically confirmed pT3/4 tumors or involvement of
      the lymph nodes are systemically and/or locally progressive after 3 to 5 years if
      only surgical or radiation therapy was performed. RESULTS: A number of studies,
      albeit exclusively retrospective, substantiated a significantly high local tumor
      control by radiotherapy after radical prostatectomy. This holds true for adjuvant
      therapy with a PSA in the "zero range" as well as with a PSA increase from the
      "zero range", whereby it must be taken into consideration that a certain
      percentage of treated patients with a PSA in the "zero-range" with or without
      positive margins actually do not need further therapy. Two retrospective studies
      demonstrated a significant better lengthening of "freedom from treatment failure"
      that is local and systemic progression of disease. Lengthening the survival time
      has, however, not yet been proven. With an increase in the PSA from the "zero
      range" after radical prostatectomy, there are indications that systemic
      metastatic spread already occurs with values higher than 2.5 to 4 ng/ml and the
      radiotherapy no longer has any curative intention. CONCLUSIONS: Adjuvant RT
      following radical prostatectomy gives better local control rates and probably
      better rates of "freedom from treatment failure" in patients with locally
      advanced prostate cancer with positive margins and probably in patients with
      negative margins. However, in retrospective studies no advantage in overall
      survival was shown.

PMID- 9235639
TI  - [Results of the treatment with fast neutrons (d.T 13 MeV) in recurrent rectal
      carcinoma].
AB  - PURPOSE: In spite of improved surgical techniques and the use of multiple
      modality treatment schemes the local recurrence rate of colorectal carcinomas
      could not be successfully reduced up to now. Besides surgical treatment of local
      recurrences in some cases radiation therapy may be indicated. PATIENTS AND
      METHOD: In the Department of Radiotherapy of the University of Munster 37
      patients with recurrent rectal carcinoma were treated between the end of 1985 and
      September 1992 either with fast neutrons alone or with a combined photon-neutron
      therapy. Eighteen patients received radiotherapy with fast neutrons (14 MeV d,T)
      alone; the tumor dose was between 10 and 15 Gy neutrons. Nineteen patients were
      irradiated with a mixed-beam schedule consisting of 30 to 45 Gy photons (X 10 MV)
      and neutron doses ranging from 5 to 10 Gy. RESULTS: In 30 patients a good or
      complete pain relief could be observed immediately after the last irradiation.
      Sixteen out of 37 patients had local tumor regrowth during the follow-up period.
      The median survival for all 37 patients was 15.9 months. The probability for
      survival was 86% after 6 months and 61% after 12 months (Kaplan-Meier). The side
      effects were slight to moderate (EORTC/RTOG I-II). CONCLUSIONS: This therapy
      showed good results concerning a fast and effective pain relief. Additionally the
      results seem to show a good effect concerning local control and overall survival
      in this negatively selected patients.

PMID- 9235640
TI  - [Influence of reduction of radiation dosage on the incidence of radiation-induced
      pneumonitis, pulmonary fibrosis and pericarditis after mediastinal irradiation in
      the treatment of lymphogranulomatosis].
AB  - BACKGROUND: The amount of radiation dose applied in the treatment of Hodgkin's
      disease is associated with the incidence of complications including radiation
      induced pneumonitis, lung fibrosis and pericarditis. Therefore, from the
      beginning of 1986, we have started to apply a radiation therapy approach with
      reduced doses in order to minimize complications while maintaining effective
      treatment. PATIENTS AND METHOD: From 1983 through 1992 141 patients suffering
      from Hodgkin's disease were included in the present study. All of them were
      treated by radiation of mediastinum. In 126 cases polychemotherapy was applied
      before radiation. From 1986 we used a reduced radiation dose in cases that were
      treated by radiation alone (affected nodal regions with 40 Gy instead of 45 Gy
      and unaffected nodal regions with 36 Gy instead of 40 Gy) as well as after
      application of chemotherapy (affected nodal regions 36 Gy instead of 40 Gy and
      unaffected nodal regions with 30 Gy instead of 36 Gy). Ninety-five patients were
      treated according to the new therapy protocol. Forty-six patients had been
      treated with the higher dosages and served as the historical control group.
      Radiation therapy included Co-60, 15-MV and 9-MV photons, and 15-MeV and 9-MeV
      electrons. Serial thoracic X-ray controls were performed. CT scans,
      echocardiographic and electrocardiographic investigations were added in selected
      cases. RESULTS: During the period from 1983 to 1992, we diagnosed radiation
      induced pneumonitis in 31% of the patients who underwent radiation therapy of the
      mediastinum. In addition, 16% demonstrated lung fibrosis and 10% pericarditis.
      After implementation of the reduced radiation dosages, the incidence of
      pneumonitis decreased from 35% to 24% (nearly significant in the 5% range), lung
      fibrosis from 24% to 12% (p < 0.05) and pericarditis from 26% to 2% (p < 0.01).
      The efficacy of treatment remained unaffected by the new therapy approach as has
      been demonstrated for cumulative survival data and recurrence-free intervals.
      CONCLUSIONS: Reduction of radiation dose in patients with Hodgkin's disease who
      undergo mediastinal radiation leads to a decrease in the incidence of radiation
      induced complications (pneumonitis, lung fibrosis, pericarditis) whereas
      treatment efficacy remains unchanged.

PMID- 9235641
TI  - [Proliferation rate and radiosensitivity. Bergonie's and Tribondeau's error].
AB  - In 1906 Bergonie and Tribondeau postulated a correlation between proliferation
      rate and radiosensitivity. Allowing for modern radiotherapeutic and
      radiobiological experience this postulate is no longer tenable.

PMID- 9235642
TI  - [Secondary malignancies in patients with Ewing's sarcoma].

PMID- 9235643
TI  - [Outcome of radiotherapy of choroid hemangioma].

PMID- 9235644
TI  - [Comparison of induction chemotherapy before radiotherapy and radiotherapy only
      in patients with locally advanced squamous cell carcinoma of the lung].

PMID- 9235645
TI  - [Outcome of CHART radiotherapy in squamous cell carcinoma of the head and neck
      and in non-small cell bronchial carcinoma].

PMID- 9235646
TI  - [The comparative clinico-laboratory characteristics of Lyme arthritis and
      reactive arthritis].
AB  - The paper presents comparative clinical and laboratory characteristics of 17
      cases of Lyme-arthritis (LA) and 28 cases of reactive arthritis (RA). LA and RA
      patients differed by age and sex. LA arose after the tick bite followed by
      erythema migrans or infection symptoms. In RA patients the above symptoms were
      absent. In LA patients arthritis was associated with typical symptoms of
      neuroborreliosis. The articular syndrome manifested similarly in LA and RA:
      arthritis was preceded by arthralgias, low limb joints and periarticular tissues
      were involved most frequently. The differences were: monoarthritis, elbow and
      shoulder joints, muscles lesions occurred more frequently in LA; polyarthritis,
      arthritis of hand and foot joints, talalgia were more common in RA. RA ran more
      actively, joint syndrome more frequently gave rise to fever. Prevalence of
      chlamydial infection in LA was close to that in RA. LA may run as RA, is
      frequently combined with Chlamydia trachomatis infection.

PMID- 9235647
TI  - [Methods for the instrumental diagnosis and verification of Lyme arthritis].
AB  - We used instrumental methods to characterise Lyme arthropathy in 79 patients with
      joint involvement and history of Lyme borreliosis. All of them had arthralgia and
      45 of them also had arthritis. Radiological examination has established
      subchondral bone sclerosis in sacroiliac joints in 68% and sacroiliitis in 29% of
      the examinees. Scintigraphy revealed polyarticular lesions in many cases.
      Ultrasound investigation has found inflammation and edema of periarticular
      tissues in the knee, shoulders and hips. The level of antibodies against the
      causative agent Borrelia (in EIA) was significantly higher in patients with
      marked signs of inflammation in ultrasound examination. Thus, the combined
      methods of examination in the diagnosis of Lyme arthritis provide the most
      complete information.

PMID- 9235649
TI  - [The characteristics of arterial hypertension in rheumatoid arthritis].
AB  - Among 138 inpatients with rheumatoid arthritis (RA) 18.1% had arterial
      hypertension (AH). AH in RA appeared in subjects with hereditary predisposition
      to AH. The presence of AH in RA is associated with rheumatoid vasculitis as the
      number of extraarticular manifestations of RA in AH patients is higher and is
      unrelated to renal affections. The levels of free radical lipid peroxidation in
      plasma and saliva are determined to a large extent by the hereditary factor in RA
      and are related to the presence of predisposition to AH.

PMID- 9235648
TI  - [The characteristics of peripheral nervous system involvement in Lyme borreliosis
      in an endemic region of Russia].
AB  - Clinical and laboratory data are available on affection of the peripheral nervous
      system (PNS) in 27 patients with Lyme-borreliosis (LB) in the endemic region of
      Russia. PNS disorders arose early, 88.9% of the patients had them within one
      month of the disease. 9 (37.5%) patients had meningoradiculoneuropathy (MRN)
      which emerged in the acute period in 77.8% of the patients. Inflammation in the
      cerebrospinal fluid was registered only in patients with clinical signs of
      meningitis. MRN developed more frequently in facial nerve neuritis (FNN) than in
      radiculopathy (RP)-80.0% and 14.3%, respectively, p = 0.01. Intrathecal synthesis
      of antibodies to B. burgdorferi in combination with pleocytosis was found only in
      FNN patients (16.7%). In 6 (37.5%) of 16 patients with neuroborreliosis
      concentrations of C-reactive protein were elevated. Its high level occurred
      significantly more frequently in RP (83%) than in FNN (17%) (p = 0.05). 5 out of
      14 LB patients exhibited high level of Willebrand factor antigen. No clear
      clinical relations between this value and PNS lesions in LB were found.

PMID- 9235650
TI  - [An evaluation of the results of the long-term treatment of rheumatoid arthritis
      patients with gold salts, aminoquinoline preparations and nonsteroidal anti
      inflammatory preparations].

PMID- 9235652
TI  - [Rheumatoid arthritis: an evaluation of treatment efficacy and some aspects of
      the physician-patient dyad].
AB  - The contribution of conventional therapeutic factors and such factors as
      psychotherapy, psychotropic drugs, psychological characteristics of the dyad
      "physician-patient" to overall treatment efficacy was measured in 111 patients
      with rheumatoid arthritis. Among non-traditional factors psychocorrection proved
      most effective. The skill of the physician to communicate with the patient, to
      inform him or her about the disease was found unsatisfactory. Special training in
      medical education to communicate with the patient is needed.

PMID- 9235651
TI  - [The intra-articular therapy with triamcinolone acetonide and betamethasone of
      rheumatoid arthritis patients: a double-blind study].

PMID- 9235653
TI  - [Combined forms of rheumatism and rheumatoid arthritis--an attempt at nosological
      interpretation].

PMID- 9235654
TI  - [Spondyloarthropathies and HLA-B27 subtypes in the populations of the Russian
      North].
AB  - The aim of the study was to investigate the role of HLA-B27 subtypes in
      development of ankylosing spondylitis and other seronegative
      spondylarthropathies. Using oligotyping techniques we studied native DNA of 219
      HLA-B27 positive natives: 88 Chukotka residents and 131 Mordovians (Russian Ugro
      Finnish population). Only subtypes HLA-B*2705 and B*2702 were revealed. A
      dominant subtype of HLA-B27 among the natives was HLA-B*2705: 99% among residents
      of Chukotka and 86% among Mordovians. It was established that among
      spondylarthropathic patients the frequency of B*2705 does not differ from its
      incidence in the studied populations. The data support the suggestion that
      several B27 subtypes and common genetic determinant of B27 gene may be involved
      in pathogenesis of spondylarthropathy.

PMID- 9235655
TI  - [The clinico-genetic characteristics of combined forms of seronegative
      spondylarthritis].
AB  - The authors present the results of clinico-genetic investigations made in 124
      patients with combined forms of seronegative spondylarthritis. The combined and
      isolated forms are compared clinically. HLA-typing results are analysed.

PMID- 9235656
TI  - [The local therapy of enthesitis and bursitis of the calcaneal area in
      seronegative spondylarthritis].
AB  - Four methods of local treatment of calcaneal enthesopathy and bursitis
      (hydrocortisone phonophoresis, laser radiation, glucocorticosteroids injections
      into the calcaneal region, physiotherapy with sinusoidal modulated currents) were
      tried in 69 patients with seronegative spondylarthritis. Local injections of
      glucocorticosteroids produced the best effect. Laser therapy or hydrocortisone
      phonophoresis is recommended in dominating pain syndrome in the calcaneal region.
      SMC therapy was not good in inflammation of tendinous-ligamentous system and
      calcaneal bursas in patients with spondylarthritis.

PMID- 9235657
TI  - [Osteoporosis: the rheumatological perspectives].

PMID- 9235658
TI  - [An epidemiological study of sacroiliitis among the native inhabitants of
      Chukotka].
AB  - For determination of sacroiliitis frequency among natives of Chukotka peninsula a
      cross-over epidemiological study was conducted. A total of 975 subjects aged 6
      years and older were examined. 324 of them (33.2%) had low back pain. X-ray of
      the pelvis was made in 239 of 324 patients. It was found that sacroiliitis
      incidence in Chukotka natives makes up 11.3%. There were marked differences in
      sex distribution: in males 17.1%, in females 5.7%, RR = 3.9. Out of Chukotka
      natives with low back pain 2.5% had ankylosing spondylitis, of patients with
      sacroiliitis 30%. A prospective study of patients with sacroiliitis recorded
      development of ankylosing spondylitis in 17% of the cases 4 years after the
      disease onset.

PMID- 9235659
TI  - [The x-ray morphometric characteristics of the spine in persons 50 and older].
AB  - To specify shape of the vertebra in relation to age and sex, the authors studied
      roentgenomorphometric evidence upon examination of the thoracic and lumbar spine
      in 600 patients over 50. Vertebral deformities were found in 45.1 and 44.5% of
      the examined males and females, respectively. Changes corresponding to vertebral
      body fracture were recorded in 12.3% of the males and 15.3% of the females. Age
      related trends in the frequency of various defects have been analyzed. The
      frequency differed in males and females.

PMID- 9235660
TI  - [Hematological "masks" in systemic lupus erythematosus].
AB  - The authors present literature data and original findings on characteristics and
      frequency of hematological disorders in SLE. Marked hemopathies are called SLE
      masks as in primary examination of the patient systemic blood diseases are not
      rejected this necessitating special investigations to exclude them. A rare case
      of SLE debut simulating paraproteinemic hemoblastosis is reported.

PMID- 9235661
TI  - [The diagnosis and treatment of anserine and trochanteric bursitis].

PMID- 9235662
TI  - [The use of rumalon in gonarthrosis].
AB  - An open prospective study in 100 industrial workers suffering from gonarthrosis
      has been performed 80 patients were treated with rumalon, 30 ml injections,
      twice/year, for 3 years in combination with ibuprofen film tabs, max daily dose
      (when required) 1800 mg. 20 patients have received ibuprofen only, the same dose.
      The control group was matched by sex, age, profession and duration of service.
      Significant differences for functional index of Lequesne between the two groups
      were detected after 1.5 years of the treatment (p < 0.05). An increase in the
      range of movements in knee joints in rumalon group was detected in comparison
      with the control group (p < 0.04). The improvement of joint function was achieved
      in 87% of the rumalon group patients while in the control group half of the
      patients got aggravation. The analysis of x-ray data has revealed no significant
      differences between the two groups. Rumalon is an effective agent against pain
      syndrome in gonarthrosis patients, preserves and improves joint function. Rumalon
      should be administered for long-term periods.

PMID- 9235663
TI  - [The endoscopic assessment of the effect of ranitidine and pirenzepine on the
      manifestations of the gastropathy induced by nonsteroidal anti-inflammatory
      preparations].
AB  - Two antiulcer drugs, ranitidine and pirenzepine belonging to blockers of H2
      receptors and selective M-cholinoblockers, respectively, were compared by
      efficacy against erosive and ulcer lesions in the upper gastrointestinal mucosa.
      A total of 62 rheumatics were examined. In patients treated by nonsteroid
      antiinflammatory drugs irrespectively of the mode of their administration the
      highest response was shown by ranitidine while pirenzepine efficacy proved poor.

PMID- 9235664
TI  - [The blood rheological properties in patients with amputation stumps and
      concomitant ischemic heart disease].
AB  - Blood rheology was compared in two groups of patients with ischemic heart disease
      (IHD). In group 1 patients low limbs were amputated. It is in them that
      rheological properties of blood were changed to the most extent. This is
      attributed to the effect of plasmic factors in the form of hypertriglyceridemia
      and hyperfibrinogenemia, sharp reduction of the total cross sectional vascular
      area (especially in high amputation) leading to blood cell damage associated with
      intensive platelet aggregation and red cell microhemolysis. Reduced muscular mass
      and resultant reduced capillary bed and deficiency of endothelial surface may
      stimulate accumulation of triglyceride-enriched very low density lipoproteins.

PMID- 9235665
TI  - [A multicenter open study of dexfenfluramine in Italy. The efficacy and safety of
      using dexfenfluramine in treating patients with simple or complicated obesity.
      The DIMOS Group].
AB  - 415 obese subjects received dexfenfluramine 15 mg twice daily for 3 months. These
      subjects were suffering from obesity with either no concomitant complications (n
      = 210) or the following concomitant complications: hypertension (n = 59), non
      insulin-dependent diabetes mellitus (NIDDM)[n = 86], eating disorders (n = 60).
      After 3 months of dexfenfluramine treatment, the mean weight loss in the patients
      who had completed the study was as follows: simple obesity 5.7(+)-0.3 kg (n =
      183); obesity with hypertension: 6.0(+)-0.3 kg (n = 57); obesity with NIDDM:
      4.2(+)-0.3 kg (n = 78); obesity with eating disorders: 6.1(+)-0.4 kg (n = 58). In
      the patients with obesity and hypertension, the mean systolic and diastolic
      pressures showed highly significant reductions. In the patients with obesity and
      NIDDM, the fasting and postprandial blood glucose and glycosylated haemoglobin
      were also highly significantly reduced. In the obese patients with eating
      disorders, the mean total caloric intake was reduced by 36%, which was highly
      significant. The mean carbohydrate and fat intake was reduced by 35.4 and 37.9%,
      respectively, whereas protein intake was only marginally reduced. Adverse events
      were usually moderate and transient, occurring at the beginning of treatment. In
      conclusion, dexfenfluramine induced significant weight loss in this group of
      obese patients, both with and without concomitant complications. A concomitant
      improvement in diabetes and hypertension was observed in patients initially
      presenting with these complications.

PMID- 9235666
TI  - [A case of Lyme borreliosis with predominant cardiac involvement (Lyme
      carditis)].

PMID- 9235667
TI  - [Rosenthal's syndrome (hemophilia C) in a patient with psoriatic arthritis (a
      clinical case)].

PMID- 9235668
TI  - [The current strategy for pathogenetic therapy in systemic scleroderma].

PMID- 9235669
TI  - [New approaches to the treatment of diseases of the periarticular soft tissues].

PMID- 9235670
TI  - [The importance of the correct diagnosis and treatment of depressions in general
      medical practice].

PMID- 9235671
TI  - [The place of Miacalcic (synthetic salmon calcitonin) in the treatment and
      prevention of osteoporosis].

PMID- 9235672
TI  - [The clinical manifestations of Lyme borreliosis in the Middle Urals and their
      association with Borrelia burgdorferi genospecies].
AB  - A parallel study was made of the clinical spectrum of Lyme borreliosis in the
      Middle Urals and genetic species of the causative agent (Borrelia burgdorferi) in
      the ticks collected at the same territory. Clinical picture of Lyme borreliosis
      in the Middle Urals is different from that in America but had similar features
      with European borreliosis: nervous disorders were more frequent than arthritis,
      high incidence of the symptoms in segments close to the place of the agent
      inoculation, low occurrence of secondary erythema and carditis. The collected
      ticks were Ixodes persulcatus. They carried B. garinii, B. afzelii, VS116 typical
      for Europe. B. burgdorferi sensu stricto characteristic for USA where arthritis
      was most common among the symptoms was not detected. Thus, the findings confirm
      suggestions on association of Lyme borreliosis clinical polymorphism in various
      geographic zones with genetic heterogeneity of the causative agent.

PMID- 9235673
TI  - [Myocardial infarction--actually an infectious disease?].

PMID- 9235674
TI  - [Screening for prostatic cancer].

PMID- 9235675
TI  - [Screening for colorectal cancer?].

PMID- 9235676
TI  - [Beta-blocking eyedrops and adverse effects].

PMID- 9235677
TI  - [Adverse effects of local use of beta-blockaders in glaucoma. A literature review
      and a survey of reports to the adverse drug reaction authority 1986-95].
AB  - The review is based on a survey of studies on adverse reactions related to
      topical administration of beta-blockers for glaucoma. Locally applied beta
      blocking agents are partially resorbed from the nasal mucosa. Concentrations
      which give rise to systemic effects occur invariably. Several reports exist of
      congestive heart failure, arrhythmias, severe respiratory symptoms, depression,
      hallucinations and confusion provoked by topical use of beta-blockers, especially
      timolol. It is impossible to estimate from the literature how often the various
      adverse effects occur. One has the impression, however, that adverse effects in
      the pulmonary and central nervous systems have not been fully considered. Between
      1986 and 1995 the Norwegian Medicines Control Authority received reports on
      adverse reactions related to topical use of beta-blockers in 17 patients. Six of
      these patients had cardiovascular and four of them severe respiratory symptoms.
      The latter group also included three fatal cases. The adverse effects seem to
      occur most frequently in the elderly, and it has been suggested that timolol
      should not be used in elderly people. Adverse effects related to treatment with
      topical beta-blockers are probably underreported in Norway.

PMID- 9235678
TI  - [Treatment of spasticity with botulinum toxin].
AB  - Spasticity is a velocity-dependent pathologic increase in muscle resistance to
      stretch, and occurs in a variety of neurologic disorders. We report our
      controlled open study using botulinum toxin A for treatment of adductor
      spasticity in five patients with advanced multiple sclerosis. Clinical evaluation
      of spasticity and stiffness of joints is based on the Ashworth Scale and grade of
      passive abduction. Three patients showed no response; the two others experienced
      an excellent and longlasting effect. We also describe briefly the different
      spastic conditions where this treatment has been used successfully.

PMID- 9235679
TI  - [Clinical diagnosis of deep venous thrombosis after hip replacement surgery].
AB  - Hip replacement surgery is associated with a high frequency of postoperative deep
      vein thrombosis. This prospective study was performed in order to investigate if
      routine bedside questioning and examination by the visiting doctor could reveal
      deep vein thrombosis in the legs of patients who had received a hip replacement.
      258 patients were evaluated. Thromboprophylaxis (dextran-70, low molecular weight
      heparin and graded elastic stockings) was given during the first week after
      operation. Bilateral venography was performed in all patients on day seven after
      operation, and showed an overall deep vein thrombosis incidence of 16%. The
      visiting doctors had not suspected deep vein thrombosis in any of the patients.
      This may have been because postoperative painful and swollen legs effectively
      masked any signs and symptoms of deep vein thrombosis. Our results show that deep
      vein thrombosis during the first week after hip replacement surgery cannot be
      discovered by clinical diagnostics. The high subclinical frequency of deep vein
      thrombosis indicates the importance of improving thromboprophylaxis in order to
      further minimise the occurrence of deep vein thrombosis and the risk of
      thromboembolic complications.

PMID- 9235680
TI  - [Psychological functions in children treated for acute lymphatic leukemia. A 5
      year follow-up of three different age groups of children].
AB  - All the children, five girls and ten boys aged 8-16 years, mean 11 years, with
      acute lymphoblastic leukemia which had been diagnosed in 1980, 1981 or 1983 and
      was still in remission in 1990, were examined. The treatment included intratecal
      methotrexate, but no irradiation. Mean age at the time of diagnosis was 4.5
      years. All the WISC-R IQ-scores were within the normal range (mean Full Scale IQ
      109, range 93-142). Six children had a high negative Verbal/Performance split
      score (mean +/- 23, range -15 to -33). This indicated dysfunction in verbal
      compared with nonverbal problem solving ability. Only one child had a high
      positive WISC-R split score (+23). Except for one child, all the scores on the
      Visual-Motor Integration Test were within the normal range. The Achenbach
      checklists were completed by parents and teachers. A small increase was found in
      the total problem scores, but most of the children were evaluated as well
      adapted.

PMID- 9235681
TI  - [Serum digitoxin in concomitant use of antiepileptics in routine therapy].
AB  - Concomitant use of digitoxin and enzyme-inducing antiepileptics may lower serum
      levels, and accordingly the effect of digitoxin, unless the higher metabolic
      clearance is compensated for by higher dosage. Use of digitoxin is almost always
      guided by serum concentration measurements. Information on a possible enzyme
      inducing effect of phenobarbital, phenytoin and carbamazepine is easily
      accessible. Compilation of serum level measurements for digitoxin showed that
      serum levels shifted towards lower values during concomitant use of phenytoin or
      carbamazepine than when digitoxin was used alone. As a consequence, the fraction
      of patients with serum levels below the therapeutic range was doubled.
      Concomitant use of phenobarbital did not cause a shift in the levels of
      digitoxin. In fact, in this group, a larger fraction of the serum level
      measurements were within the therapeutic range. Thus, the dosage of digitoxin
      appears to be fully compensated during concomitant use of phenobarbital, but
      obviously deserves attention during concomitant use of phenytoin or
      carbamazepine.

PMID- 9235682
TI  - [May-Hegglin's syndrome. Hereditary macrothrombocytopenia with inclusions in
      neutrophil granulocytes].
AB  - May-Hegglin's anomaly is a rare, autosomally dominant inherited syndrome not
      previously described in Norway. We report two cases, sisters with characteristic
      light and electron microscopic inclusions in the granulocytes, thrombocytopenia
      and giant platelets. The relevant literature is briefly reviewed.

PMID- 9235683
TI  - [Anaphylactic reaction to N-acetylcysteine after poisoning with paracetamol].
AB  - Paracetamol is among the most common substances consumed in self-poisoning
      attempts. The recommended treatment is intravenous N-acetylcysteine. Adverse
      reactions to this treatment are relatively common, but are rarely serious. The
      article reports and discusses a patient who had an anaphylactoid reaction to N
      acetylcysteine after an overdose of paracetamol. This reaction was most probably
      an acute toxic effect of N-acetylcysteine, and not a result of an immunologic
      hypersensitivity reaction. Reducing the infusion rate of the initial loading dose
      might reduce the risk of adverse reactions. Recent guidelines recommend giving
      the loading dose over 60 minutes, instead of 15 minutes.

PMID- 9235684
TI  - [Subacute cutaneous lupus erythematosus].
AB  - Subacute cutaneous lupus erythematosus (SCLE) is recognized as a variant of
      Systemic lupus erythematosus (SLE) and affects mainly middle-aged Caucasian
      women. The clinical picture is characterized by typical skin lesions, joint or
      muscle pain and occasionally arthritis. Serious systemic manifestations such as
      affection of the central nervous system and kidneys are rarely observed. Most
      SCLE patients are strongly photosensitive, which is associated with the presence
      of anti-SSA and/or anti-SSB antibodies. The disease can mimic both Sjogren's
      syndrome and SLE. The course is characterized by exacerbations and remissions.
      SCLE sometimes occurs concomitantly with other diseases of both a rheumatological
      or non-rheumatological nature, and it has also been discussed whether SCLE might
      be an example of a paraneoplastic syndrome. Treatment with hydroxychloroquine is
      usually effective. Five patients with SCLE are described.

PMID- 9235685
TI  - [Neuropsychiatric symptoms and findings in systemic lupus erythematosus ].
AB  - Systemic lupus erythematosus (SLE) frequently involves the central nervous
      system. The clinical presentation is highly variable and heterogeneous. The
      involvement of the central nervous system is often reflected in minor or major
      neuropsychiatric symptoms. We describe three cases of this neuropsychiatric lupus
      erythematosus. A variety of laboratory tests are essential in order to establish
      the correct diagnosis of neuropsychiatric SLE. We discuss the usefulness of
      magnetic resonance imaging in both a diagnostic setting and as a tool for
      improving the understanding of the pathogenesis of neuropsychiatric SLE.

PMID- 9235686
TI  - [Genetic and environmental factors in colorectal cancer. Mutations in the
      familial adenomatous polyposis gene].
AB  - The incidence of colon cancer has increased during the last 30 years in Norway
      and is now the second most common newly diagnosed type of cancer in women and the
      third in men. Familial adenomatous polyposis, hereditary colorectal cancer, is
      caused primarily by inactivation of the tumour suppressor gene adenomatous
      polyposis coli (APC). The protein coded for by this gene has a possible role in
      cell-cell signalling or adhesion by binding to catenins which bind to the cell
      adhesion molecule E-cadherin, or in anchoring the cytoskeleton. Both germ-line
      and somatic APC gene mutations result in a truncated protein, due to introduction
      of a stop codon. The positions of the germ-line mutations seem to correlate with
      the seriousness of polyposis. The food mutagen PhIP causes specific mutations in
      the Apc gene in rats, and is a possible environmental mutagen also in humans. The
      Min mouse with mutated Apc-gene is a good model for studies of both induction and
      prevention of inherited and sporadic intestinal cancer.

PMID- 9235687
TI  - [A simple method for endoscopic placement of a nasojejunal feeding tube].
AB  - The aim of this paper is to describe a simple, nonsurgical method for endoscopic
      placement of a nasojejunal feeding tube. A stylet inserted in the tube
      facilitates nasogastric intubation. A thread on the tip of the tube is grasped
      with a biopsy forceps inserted through an endoscope, and the tube can be placed
      in the distal part of the duodenum under direct endoscopic inspection. By means
      of a guide wire the tube can be pushed further to the desired position in the
      upper part of the jejunum. The endoscope can now be removed while pressure is
      exerted on the stylet, thus preventing the tube from dislocating. By this method,
      oral-nasal transfer of the tube is avoided, the tube is placed in the upper
      jejunum under direct endoscopic inspection, and the stylet inserted in the tube
      facilitates intubation and prevents it from dislocating when the endoscope is
      withdrawn.

PMID- 9235688
TI  - [Is it possible to influence the utilization of antibiotics?].
AB  - Excessive and inappropriate use of antibiotics in hospitals contributes to the
      development of antibiotic resistance and higher costs. At Aker University
      Hospital the use of antibiotics and the associated costs have increased over the
      last years. In an attempt to reverse this trend we introduced guidelines for
      prescribing antibiotics, based on knowledge of the local pattern of resistance.
      The programme resulted in a reduction of 9% in the use of antimicrobial drugs and
      of 24% in the associated costs, i.e. a saving of NOK 2.2 million in one year.
      From 1995 to 1996 there was a further reduction in antibiotic consumption by 7%.
      We conclude that guidelines for use of antibiotics, and relevant information, can
      be useful tools in influencing the prescription of such drugs.

PMID- 9235689
TI  - [Is there a basis for prostatic cancer screening in Norway?].

PMID- 9235690
TI  - [To conceive a child is not a human right].

PMID- 9235691
TI  - [AIDS and immigration].

PMID- 9235692
TI  - [Infected at work--an occupational hazard in health care].

PMID- 9235693
TI  - [Methadone maintenance treatment--no universal solution].

PMID- 9235694
TI  - [So called diabetes in pregnancy--a new public disease?].

PMID- 9235695
TI  - [A good family practice organization--significant for quality development of
      entire health service].

PMID- 9235696
TI  - [The human genome project--with rapid speed towards new possibilities].

PMID- 9235697
TI  - [Can we afford good health services? Can prioritization solve the problems?].

PMID- 9235698
TI  - [Surgical treatment of morbid obesity].

PMID- 9235699
TI  - [Two physicians for the patient with cancer?].

PMID- 9235700
TI  - [Hypothyroidism--easy or difficult diagnosis?].

PMID- 9235701
TI  - [Thyroidectomy in Norway].

PMID- 9235702
TI  - [Thyroidectomy in Aust-Agder. A 15-year material 1979-92].
AB  - In the 15-year period from 1978 to 1992 344 consecutive patients unselected
      underwent thyroid surgery. The annual operative incidence per 100,000 inhabitants
      was 2.5 for cancer, 2.3 for Graves' disease and 20.5 for benign nodules. The
      patients were followed up from 3 to 18 years after surgery. The operative
      mortality was zero, but complications were recorded in 5.8% of the cases. There
      was permanent hypoparathyroidism in four patients and unilateral permanent vocal
      cord paralysis in six. No patients had bilateral paralysis. For better selection
      in cases with nodular goiter, fine needle aspiration cytology should be standard
      procedure. The results presented are in accordance with others which relate to
      benign nodular goiter. However, with regard to the smaller groups, cancer and
      Graves' disease, results could possibly be improved by centralizing the operative
      treatment for each speciality, which would have to be defined.

PMID- 9235703
TI  - [Surgical treatment of obesity. Is gastric wrapping an alternative?].
AB  - To remedy the disabling side effects of gastric banding, a group of eleven
      patients were re-operated with gastric wrapping. Encouraging results led us to
      perform primary gastric wrapping straight away in fourteen additional patients.
      There were few serious complications. A comparison of the performance of the two
      groups is based on observations four years later. In the first group, a mean body
      mass-index (BMI) of 41 +/- 4 SD was noted before banding, 32 +/- 8 SD at
      conversion to wrap and 31 +/- 9 SD at control. The mean BMI in the second group
      was reduced from 40 +/- 5 SD to 32 +/- 6 SD after primary gastric wrapping.
      Radiographic control showed a shortening of the wraps in both groups, with pouch
      formation in half of the cases, uncorrelated to weight loss. It appears that
      gastric wrapping can be a useful revisional procedure in patients who do not
      tolerate gastric banding. Primary gastric wrapping produces results comparable to
      those of gastric banding. Modifications in our version of gastric wrapping are
      discussed with reference to the original method and other surgical approaches.

PMID- 9235704
TI  - [The project Better Cancer Care in Buskerud].
AB  - A project called Better cancer care in Buskerud was started in 1991 in the county
      of Buskerud, in Norway. The main objective was to improve the out-patient
      services for cancer patients at the central hospital. In this article we describe
      the activities at the out-patient clinic during the period 1991-1993. The clinic
      was staffed by two oncologists and two cancer nurses. A total of 8060
      consultations were held with patients during the period. Breast cancer patients
      comprised the largest group (30%), followed by patients with gastrointestinal
      cancer (24%) or malignant lymphoma (13%). The hospital's Department of Surgery
      was particularly relieved to hand over the administration of chemotherapy. The
      number of patients who received radiotherapy at the nearest cancer centre did not
      increase, however, during the period. We conclude that the project in Buskerud
      was a success, and that most of the objectives were achieved.

PMID- 9235705
TI  - [Surgical treatment of carcinoid bronchial tumor].
AB  - During the period 1977-95, 20 patients underwent surgery for carcinoid tumour in
      the bronchus at the University Hospital of Trondheim (n = 16) and Innherred
      County Hospital (n = 4). All the tumours were typical carcinoid tumours. Median
      age of the patients was 41 years (range 16-78 years). The observation period
      averaged 7.5 years (0.5-18 years). The most common symptoms were cough, dyspnoea,
      wheezing and pneumonia. One patient had carcinoid syndrome. Chest X-ray were
      negative in three of the patients. Bronchoscopy was carried out in all the
      patients. Biopsies were taken in ten of them, and the diagnosis was conclusive in
      five cases. Lateral thoracotomy was performed in all the patients. The surgical
      procedures were lobectomy (15), segmental/wedge resection (3), bronchotomy with
      tumour resection (1) and sleeve resection (1). 19 patients were still alive at
      the time of follow-up, with no tumour recurrence. One patient died from cerebral
      stroke eight years after surgery. Good long-term results were found, and the
      study supports the use of limited lung resection or bronchoplasty operations to
      treat carcinoid tumour in the bronchus if the primary tumour is localised and
      there are no metastases.

PMID- 9235706
TI  - [Bronchial resections].
AB  - In the period 1982-96, 18 bronchial resections were performed. Simple resection
      was carried out in eight patients, and in ten lung tissue was also removed; six
      upper lobes and three middle lobes were involved, and in one patient bilobectomy
      was necessary. The histologic diagnosis was carcinoid in 15 cases (83%),
      mucoepidermoid carcinoma in two, and in one case neurofibroma. Two patients had
      postoperative complications, but both recovered completely. All patients were
      followed up regularly by bronchoscopy. One patient had carcinoid with liver and
      bone metastases at the time of operation in 1989, but is still alive. Another
      died from metastases, the rest were in good condition at the most recent follow
      up. Bronchial resection is a safe procedure which should be preferred to standard
      pneumonectomy, in order to save as much lung tissue as possible. The frequency of
      bronchial resections for carcinoids (compared with standard pneumonectomy) was
      60%.

PMID- 9235707
TI  - [Krukenberg tumor. A seldom considered condition?].
AB  - In 1896, Krukenberg described what he presumed was a new type of primary ovarian
      neoplasm. The true metastatic nature of this lesion was established six years
      later. Some 10% of all ovarian malignant lesions are regarded as metastatic. Of
      these, approximately 50% are Krukenberg tumours. The tumour is well defined
      histologically and is usually secondary to a tumour in the gastrointestinal
      tract. We describe the case of a 48 year old woman with gastric cancer who, three
      years after diagnosis and subsequent total gastrectomy, was referred to us for
      observation with peritoneal involvement. We stress the importance of careful
      clinical and radiological follow-up of female patients with gastrointestinal
      cancer.

PMID- 9235708
TI  - [Discitis in children. Description of the condition illustrated by two case
      reports].
AB  - Discitis in children is usually a self-limiting and non-infectious inflammation
      in the intervertebral disc. The symptoms are diffuse and vary from patient to
      patient; most often back pain, walking difficulties, crying and irritability.
      Radiology is often negative initially, and there may be a long delay from onset
      of symptoms to diagnosis. Magnetic resonance imaging may help in making an early
      diagnosis. Treatment is controversial; most authors recommend antibiotics only in
      special cases. It is important to be aware of the condition in order to avoid
      unnecessary investigations and treatment. We describe two patients, to illustrate
      the etiology, symptoms and treatment.

PMID- 9235709
TI  - [CT combined with arterial portography. A sensitive method for evaluation of
      liver tumors].
AB  - During the period 1994-95, 22 patients were examined with CT during arterial
      portography for evaluation of hepatic tumours. The majority, 20 patients, had
      metastases from colon cancer. All patients were candidates for liver resection.
      In the series of patients described here, this process detected additional
      lesions in four more of the patients than found with any other imaging
      techniques. This supports that CT during arterial portography is the most
      sensitive method for detecting small malignant hepatic tumours, and for
      localizing them in relation to liver segments and major vascular structures.
      Optimal results are obtained in the absence of diffuse parenchymal disease and
      portal hypertension. Non-tumourous perfusion defects limit the accuracy of this
      technique, but such defects have characteristic locations and appearance. In
      difficult cases the technique should be correlated with ultrasonography and MR.

PMID- 9235710
TI  - [Computer tomography of pathological neck lesions].
AB  - The introduction of high resolution computed tomography (CT) has significantly
      improved the quality of imaging of neck masses. Incremental dynamic scanning
      immediately after a quick bolus injection of contrast medium is essential in a
      majority of patients in order to obtain an optimum of information. This is
      especially true in the identification, mapping and staging of malignant lesions,
      which is the main indication for the examination. CT is also very sensitive, and
      yields detailed information about the location and extent of cystic and other
      benign lesions. Owing to the low attenuation of fat, the examination is very
      specific with respect to lipomas. CT has low specificity in the differentiation
      between benign and malignant lesions, and between cysts and solid tumours of the
      thyroid gland. In thyroid and parathyroid imaging other modalities such as
      ultrasound and scintigraphy are often more specific.

PMID- 9235711
TI  - [Sjogren's syndrome. New diagnostic aspects].
AB  - European criteria for classification of Sjogren's syndrome have recently been
      developed and evaluated. We report the clinical and laboratory findings in 96
      patients with primary Sjogren's syndrome who have been classified according to
      these new criteria. In our patient population the latency from appearance of the
      first symptom to diagnosis was 11 years. In addition to sicca symptoms in mucous
      membranes, the dominant symptoms were periodic fatigue (92%), arthralgia (82%),
      hoarse voice (71%), dry cough (54%) and diarrhoea (51%). Antibodies to the
      nuclear antigens SSA and SSB were found in respectively 22.2% and 15.6% of the
      patients. Two out of ten patients with both anti-SSA and anti-SSB antibodies gave
      birth to a child with heart block.

PMID- 9235712
TI  - [Hormone replacement therapy and cancer].
AB  - During the last 25 years, the question of hormone replacement therapy (HRT) has
      been in focus. HRT has proved to reduce the risk of cardiovascular diseases and
      osteoporotic fractures substantially. However, controversies still remain as
      regards cancer risk when patients with a history of breast or endometrial cancer
      are prescribed HRT. Women who take progestins along with oestrogen are not at
      higher risk of developing endometrial cancer than postmenopausal women who do not
      take oestrogen are. An overall assessment indicates that long-term HRT may
      increase the risk of breast cancer slightly. Oestrogen users seem to have a lower
      risk of developing colon cancer. Prescribing HRT to selected women after a
      history of endometrial or breast cancer is no longer contra-indicated, but
      prospective randomised trials are required to test the effect of HRT on overall
      survival.

PMID- 9235713
TI  - [An alternative to current waiting list guarantee].

PMID- 9235714
TI  - [Organ donation--an issue for you?].

PMID- 9235715
TI  - [Can you afford to serve as military physician?].

PMID- 9235717
TI  - [Ethical problems of terminal care].

PMID- 9235716
TI  - [Progress and decline in Ngami].

PMID- 9235718
TI  - [Is homeopathy badly documented?].

PMID- 9235719
TI  - [Physicians and drug handling. Needs of change both inside and outside hospital].

PMID- 9235720
TI  - [Use of snuff and health hazards].

PMID- 9235721
TI  - [The debate on leadership].

PMID- 9235722
TI  - [Not exactly accurate about salaries to fellowship recipients].

PMID- 9235723
TI  - TRANSFUSION:the first decade. Volume 7.

PMID- 9235724
TI  - [Prevention and treatment of febrile neutropenia].
AB  - Many chemotherapy regimens are associated with variable periods of
      myelosuppression. In cancer patients, neutropenia (less than 500
      neutrophils/microL) is the most important risk factor for infections. The
      incidence and severity of infectious complications are related to depth and
      duration of neutropenia, with the highest risk if neutrophils are less than
      100/microL for more than a week. The period required for neutrophil recovery is
      usually short with standard regimens, but prolonged after high dose chemotherapy
      followed by autologous bone marrow transplant (-ABMT) or peripheral blood stem
      cell (PBSC) infusion. Under these conditions, the administration of granulocyte
      colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating
      factor (GM-CSF) accelerates neutrophil recovery and shortens the duration of
      hospitalization. In standard chemotherapy settings, prophylactic use of CSF's is
      a matter of debate. Several studies have reached contrasting conclusion, but,
      combining effectiveness and costs, it results that this use of CSF'S is not to be
      recommended unless the risk of infections (elderly patients, reduced marrow
      reserve) is high. The administration of G-CSF or GM-CSF to a febrile neutropenic
      patient (cfr CSF's therapy) shortens the duration of neutropenia, although no
      great clinical benefits are evident. Nevertheless the identification of subsets
      of patients with additional risk factors (i.e. absolute neutrophil count <
      100/microL at the onset of fever or delayed neutrophil recovery) should be
      helpful in establishing the role of CSF's therapy. When prolonged periods of
      severe neutropenia (less than 500 neutrophils/microL) are expected, antibiotics
      should be prophylactically administered. Fluoroquinolones seem to be the optimal
      choice in heavily myelosuppressed patients (ie. bone marrow transplant
      recipients). Fluoroquinolones are effective in reducing the frequency of gram
      negative bacteremia, but, because of incomplete coverage, gram-positive
      infections are becoming increasingly problematic. The association with an agent
      that can be absorbed orally, active against gram-positive cocci, seems to be an
      effective strategy. Fungal infections are an important cause of morbility and
      mortality in severely neutropenic patients. Safety and efficacy of antifungal
      triazoles and the lipid formulations of amphotericin B used prophylactically
      still require investigation. In patients at high risk for fungal infections,
      monitoring cultures are predictive for systemic mycoses and should guide
      prophylactic and therapeutic choices. The standard treatment of oncologic
      patients with potential infectious neutropenia complications is admission to the
      hospital and treatment with broad-spectrum intravenous antibiotics. Until third
      generation cephalosporin and carbapenems became available, most neutropenic
      febrile patients were treated with associations of an aminoglycoside plus a beta
      lactam. Monotherapy with the new antibiotics has proven to be effective as an
      association therapy and offers advantages in terms of cost and tolerability.
      Whether or not vancomycin is included in the initial antibiotic regimen should be
      decided on the basis of epidemiological consideration (i.e. prevalence of
      meticillin-resistant Staphylococcus aureus or Staphylococcus mitis in certain
      centers). Antifungal therapy is indicated in neutropenic patients who remain
      febrile after one week of broad-spectrum antibiotics or have recurrent fever.
      Amphotericin B should be promptly administered in patients suspected of invasive
      mycoses. Selected patients with fever and neutropenia, that can be identified on
      the basis of reduced risk of severe complications, do not need hospitalization.
      In the first reports, outpatient treatment has proven to be effective, cost
      saving and well received by patients, but further studies are needed to
      accurately define low risk status and the optimal home antibiotic regimens.

PMID- 9235725
TI  - [Treatment of pain in oncology].
AB  - Basic guidelines for cancer pain treatment can be found in many different
      handbooks published in the last years. Particularly those of the World Health
      Organisation published in 1986 and revised in 1996, furnish useful indication for
      cancer pain treatment. The authors therefore focused on resuming the most recent
      development in this field. In the research regarding alternative routes of
      administration of opioids in alternative to the oral route, the rectal
      administration of morphine and methadone and the transdermal route for fentanyl
      have proved to be efficacious. The subcutaneous route (for morphine) as well as
      the intravenous, peridural and subaracnoid routes, being known for some time are
      not taken in consideration in this paper. Various studies suggest that
      alternative routes are necessary in 53-70% of patients in their last days or
      months of live. The most frequent causes for the need to stop oral administration
      are dysphagia, nausea, and uncontrollable vomiting, bowel obstruction,
      malabsorption, cognitive failure, coma, and pain syndromes requiring anaesthetics
      which need be administered via the spinal route. Among the drugs, tramadol seems
      to be effective in the control of moderate pain. Tramadol is a centrally acting
      analgesic drug; it has an agonist effect on mu 1 receptors of opioids and acts
      also by inhibiting the re-uptake of noradrenaline and serotonine which activates
      descending monoaminergic inhibitory pathways. Recent clinical studies revealed
      that pamidronate has an analgesic effect in pain due to bone metastasis.
      Pamidronate is part of the biphosphonates, which are active on bone metabolism
      and are usually being used for the treatment of hypercalcaemia in cancer. The
      authors also describe briefly the indication of ketamin in association with
      morphine for the treatment of neuropathic pain.

PMID- 9235726
TI  - [Evaluation of quality of life in oncology. Rationale and objectives of the first
      phase of the Quality of Life in Oncology project].
AB  - Although the subjective nature of quality of life perception is generally
      accepted, less attention has been paid to the procedure of selecting domains to
      be explored with questionnaires. In most cases domains are selected by panel of
      experts. It is not known whether these domains are relevant for the patients.
      Moreover, questionnaires developed in 'foreign' countries may not be culturally
      sound or relevant for patients living in different cultural background. In order
      to explore what really contributes to quality of life of Italian patients, a
      survey was conducted with the aim of identifying any dimension of quality of
      life, positively or negatively impacted on from the illness and therapies. A
      sample of two hundred and eighty eight cancer patients with previously specified
      characteristics (primary tumor, stage of disease and place of residence) were
      identified. After consenting to partecipate to the study, a staff member (a
      physician, a nurse or a psychologist) asked the patient to complete an open-ended
      questionnaire in the out-patient clinic or at home. This questionnaire, partially
      derived from a study by Padilla et al. made up of 5 questions: 'What does the
      term quality of life mean to you?', 'What contributes to a good quality of
      life?', 'What contributes to a poor or bad quality of life?', 'Which either
      physical or psychological symptom interferes with your quality of life?', 'State
      any positive or negative change in your quality of life, due to illness or
      treatments'. The first question was asked to explore the meaning of quality of
      life for the patient; the second and third question were asked to determine the
      contents of quality of life not health related; the fourth question and the diary
      provided information about quality of life contents related to his own experience
      of disease. Two hundred and forty eight questionnaires (86.1%) were obtained from
      7 Cancer Centres participating to the study (Genova, Milano, Roma, Perugia,
      Napoli, Cagliari, Palermo). All the questionnaires were transcribed and
      subsequently broken down in phrases on a form that allowed coding. Three raters
      (a research nurse, an oncologist and a clinical psychologist) made the content
      analysis using as conceptual framework the list of domains identified by the
      Italian Society of Psycho-Oncology. The present study shows the possibility to
      define the content domain of quality of life attributes for cancer patients,
      using patients as experts.

PMID- 9235727
TI  - [Recent improvements in antiemetic therapy].
AB  - In the past few years important progress in the prevention of chemotherapy
      induced nausea and vomiting has been made mainly thanks to the introduction of
      the 5-HT3 receptor antagonists in clinical practice (ondansetron, granisetron,
      tropisetron). In the prevention of acute emesis induced by cisplatin, an
      intravenous combination of a 5-HT3 receptor antagonist plus single dose
      dexamethasone (20 mg) should be considered the treatment of choice. This is also
      the case in the prevention of acute emesis induced by moderately emetogenic
      chemotherapy (intravenous cyclophosphamide, doxorubicin, epirubicin, carboplatin,
      used alone or in combination), but high and repeated doses of dexamethasone
      should be used (8 mg intravenously plus 4 mg orally every 6 hours for four doses
      starting contemporarily to chemotherapy administration). Several-well conducted
      double-blind comparative studies among intravenously administered 5-HT3 receptor
      antagonists have been carried out. Almost all showed that they have identical
      antiemetic activity and tolerability. Therefore, the choice among 5-HT3 receptor
      antagonists should be based only on their acquisition cost in each country. In
      the prevention of delayed emesis (from day 2 to day 4) induced by cisplatin oral
      metoclopramide (0.5 mg/kg or 20 mg every 6 hours for four doses daily) and oral
      ondansetron (8 mg twice daily), both combined with dexamethasone, showed similar
      antiemetic efficacy. Metoclopramide plus dexamethasone should be considered the
      antiemetic regimen of choice due to its lower cost. Ondansetron plus
      dexamethasone is a valid alternative regimen that should be preferred in patients
      who not tolerate metoclopramide and in patients who suffer from acute vomiting.
      In the prevention of delayed emesis induced by moderately emetogenic chemotherapy
      oral dexamethasone or oral ondansetron showed a good antiemetic efficacy, but the
      results from a recently published study seem suggest the necessity to treat only
      patients who present acute vomiting or moderate-severe nausea. In fact, patients
      obtaining complete protection from vomiting and nausea (or at most mild acute
      nausea) have a very low incidence of delayed emesis.

PMID- 9235729
TI  - [Physiological examination of micturition].

PMID- 9235728
TI  - [Swimmer's ear and otitis externa].

PMID- 9235730
TI  - [Diagnosis of incontinence].

PMID- 9235731
TI  - [Imaging and functional diagnosis of malignant skeletal disorders].

PMID- 9235732
TI  - [Occupational environment and strain induced gout. A review of epidemiological
      studies of the connection between occupational environment and coxarthrosis].
AB  - Osteoarthrosis of the hip is a frequent complaint with multifactorial causal
      relations. The causes have hitherto not been associated with the work
      environment. Through a systematic literature search 15 epidemiological studies
      dealing with the relation between occupation or factors in the work environment
      and coxarthrosis were found. A critical evaluation finds that farmers and
      construction workers have an increased risk of contracting coxarthrosis. Work
      that is strenuous for the hip such as lifting and ladder climbing might also be
      risk factors. Prevention of heavy work involving the hip is proposed as a
      consequence of this knowledge. The Danish Workers Compensation Act should also
      take these findings into consideration.

PMID- 9235733
TI  - [Persistent pulmonary hypertension in newborn infants].
AB  - On the basis of a review of the literature, a survey is presented concerning
      persistent pulmonary hypertension of the newborn. In this article the authors
      focus on the pathophysiology, diagnostic criteria and treatment, including
      mechanical ventilation, pharmacological vasodilation and extracorporal membrane
      oxygenation. Particular emphasis is placed on the treatment of the condition with
      inhaled nitric oxide. Nitric oxide is a selective pulmonary vasodilator and able
      to improve ventilation/ perfusion mismatching in cases where there is an
      affection of the pulmonary parenchyma. Data from randomized trials with close
      long-term follow-up is necessary before routine nitrogen oxide treatment can be
      recommended.

PMID- 9235734
TI  - [Otitis externa among users of private swimming pools].
AB  - The purpose of this study was to detect risk factors for developing otitis
      externa (OE) with special regard to swimming in private pools in holiday houses.
      Data were collected in a retrospective case-control study from June to October in
      1993 and over the same period in 1994. Patients who had OE diagnosed by a general
      practitioner were included. In 1993 controls were 134 guests from 27 holiday
      houses where nobody got o.e. during their stay. The number of cases was 35. In
      1994 the design was changed so that controls were the 95 healthy inhabitants from
      the same houses as the 23 cases. The amounts of time spent in the pools and the
      total bacteria count in the water were significant risk factors for developing
      OE. Pseudomonas aeruginosa was found in 80% of the ear swabs of the casegroup. In
      1993 30% and in 1994 83% of the pools fulfilled the requirements for public pools
      set by the Danish authorities.

PMID- 9235735
TI  - [Campath-1H--a monoclonal antibody for treatment of non-Hodgkin's and chronic
      lymphatic leukemia].
AB  - Treatment with antibodies in patients with lymphoproliferative diseases was,
      until recently, limited to phase I studies due to limited response or subsequent
      development of anti-globulin response. The introduction of the hybridoma
      technique during the 1970s facilitated large scale production of antibodies,
      including the development of the Campath rat-antibodies. The epitope was launched
      against CD52, a glycoprotein present in large amounts on the surface of
      lymphocytes, and the primary use was in-vitro depletion of bone marrow from
      allogeneic bone marrow transplantation donors. The development of the human
      Campath-1H antibody was successful in 1988, leading to minimized anti-globulin
      response when used in vivo, and large multi-center studies were initiated. In
      this study we present an overview of the preclinical and clinical experiences
      with Campath-1H, including data from patients treated with the antibody in our
      clinic.

PMID- 9235736
TI  - [Soft tissue changes in adults with acquired growth hormone deficiency during
      substitution treatment. A double-blind, randomized, placebo-controlled study
      after a year of treatment].
AB  - The aim of the study was to assess the influence of growth hormone (GH) on body
      composition in 29 adult persons with acquired growth hormone deficiency (GHD).
      The study was a double-blind placebo-controlled study of one year's duration. The
      treatment consisted of daily subcutaneous injections of GH (2.0 IU/m2,
      Norditropin) or placebo. Before and after one year's treatment, the patients were
      hospitalized for measurement of Dual-Energy X-ray Absorptiometry (DXA) in order
      to assess body composition (Fat mass (FM) + Lean Body Mass (LBM). In addition,
      fasting serum Insulin-like Growth Factor (IGF-I) was collected. The study showed
      a 200% increase in serum IGF-I. Regarding LBM a 5.7% increase was seen, and this
      was primarily due to an increase in LBM of the extremities, whereas FM was
      reduced by 21.5% mainly located truncally. Our data demonstrate that favorable
      changes in body composition are maintained during long-term, controlled GH
      treatment, which loads support to the concept of GH substitution in GH-deficient
      adults.

PMID- 9235737
TI  - [Erysipelothrix rhusiopathiae bacteremia after dog bite].
AB  - A case of erysipeloid with bacteraemia caused by Erysipelothrix rhusiopathiae
      (ER) in a previously healthy 41-year old man is presented. The bacterium was
      probably introduced by the bite of a dog. He was treated successfully with
      penicillin V. The ER bacteraemia occurred without complications of endocarditis.

PMID- 9235738
TI  - [Chronic unilateral maxillary sinusitis caused by foreign bodies in the maxillary
      sinus].
AB  - Chronic maxillary sinusitis is a common condition. The disease is most often
      caused by blockage of the sinus ostia or presence of an oroantral fistula. We
      report two cases of unilateral chronic maxillary sinusitis associated with
      foreign bodies in the maxillary sinus. In the first case the foreign body
      consisted of dental amalgam, in the second case of two silastic sponges left
      behind from a former operation because of "blowout" fracture. In the case of
      benign chronic maxillary sinusitis and foreign bodies, functional endoscopic
      sinus surgery (FESS) preceded by a CT-scan is an excellent approach, by which
      diagnosis as well as treatment can be achieved with minimal surgical trauma.

PMID- 9235739
TI  - [Scientific misconduct. A committee and its function].

PMID- 9235740
TI  - [Itching and warm water bacteria--making mountain of a molehill].

PMID- 9235741
TI  - [Silicone breast implants and connective tissue diseases].

PMID- 9235742
TI  - [Danish medical research--in international journals and in the Ugeskrift].

PMID- 9235744
TI  - [The new "reversed G-system"].

PMID- 9235743
TI  - [Gentacoll. A combined collagen-gentamicin preparation].

PMID- 9235745
TI  - [Barotherapy in the combined treatment of lymphovenous insufficiency of the lower
      extremities].

PMID- 9235746
TI  - [Herniolaparoscopy].

PMID- 9235747
TI  - [Pseudomembranous colitis and "intestinal sepsis" as a consequence of
      dysbacteriosis due to antibiotics].
AB  - Based upon 11 personal observations and data of literature the authors describe
      etiopathogenesis, clinical picture, diagnosis and treatment of pseudomembranous
      colitis. The recommended complex therapy resulted in the recovery of all the
      patients.

PMID- 9235748
TI  - [The medical aspects of the rehabilitation of patients with congenital heart
      defects and the problems of their social integration into modern society].
AB  - Treatment of 500 patients was used as a basis for the development of a complex
      stepwise programme of rehabilitation of patients with congenital heart diseases
      (CHD). It was noted that for a valuable social integration of people with CHD
      into the modern society it was necessary to perform not only the indicated,
      adequate and timely operations but also the inescapable measures for the
      improvement of their physical and psychophysiological adaptation. The following
      job in remote periods of observations of the patients operated upon must take
      into account its conformity to functional possibilities of energy expenditure for
      the chosen occupation and should be effected with the individually accessible (or
      indicated) level of the physical tension taken into consideration.

PMID- 9235749
TI  - [Rupture of the posterior wall of the left ventricle after mitral valve
      prosthesis].
AB  - Rupture of the posterior wall of the left ventricle took place in 17 (1.2%) out
      of 1447 patients operated upon for the replacement of the mitral valve. Among
      them there were 13 13 early and 4 delayed ruptures. The methods used for
      liquidation of this complication are described. Four patients recovered (2
      patients with early, 1 with a delayed rupture and 1 with a developed false
      aneurysm of the left ventricle). Literature data concerning the prevention of
      ruptures of the left ventricle and methods of their liquidation are presented.

PMID- 9235750
TI  - [Gastric resection in peritonitis combined with 4 peptic ulcer complications].

PMID- 9235752
TI  - [Peritonitis chronica fibrosa encapsulans].

PMID- 9235751
TI  - [Acute appendicitis complicated by destruction of the large intestine and septic
      shock].

PMID- 9235753
TI  - [Plasmapheresis and pain].

PMID- 9235754
TI  - [Accreditation of the surgical service in the ambulatory component as a factor in
      raising the quality of its activities].

PMID- 9235755
TI  - [The 1st International Conference on Emergency Surgery (Belgrade, Yugoslavia, 25
      28 September 1996)].

PMID- 9235756
TI  - [Science or surgery? 1927].

PMID- 9235757
TI  - [The prevention and treatment of postoperative thrombosis of the deep veins of
      the lower extremities (II. Treatment)].

PMID- 9235758
TI  - [Internal appendicular-organic fistulae--a complication of acute appendicitis].

PMID- 9235759
TI  - [The suturing, plastic repair, prosthesis and autoplasty of defects in the
      interventricular septum without artificial circulation].
AB  - The authors have made an analysis of 1500 operations using a unique technology of
      closure without perfusion of the interventricular septum defects of the heart
      under conditions of hypothermia. Lethality was 1.7%, frequency of recanalization
      of the defects was 0.9%.

PMID- 9235760
TI  - [Nodular goiter and thyroid cancer].
AB  - The author analyzes 151 cases of differentiated carcinoma of the thyroid gland
      and 112 cases of nodular nontoxic goiter. In 83.5% of patients with carcinoma of
      the thyroid gland there was no "goiter anamnesis", in 71.5% of the carcinoma
      patients the tumoral node was located in the unchanged tissue of the thyroid
      gland, in 28.5% the nodular goiter was found in the contralateral lobe and only
      in 10% of observations carcinoma took place against the background of the nodular
      goiter and adenoma. There is no reason to consider the nodular goiter as pre
      cancer, and the surgical treatment of the nodular goiter as prophylaxis of
      carcinoma of the thyroid gland. The indications to operation for benign nodular
      formations of the thyroid must be restricted.

PMID- 9235761
TI  - [The results of using different variants of esophago-intestinal anastomoses in
      gastrectomy].

PMID- 9235762
TI  - [The importance of studying acid gastric secretion for the prognosis of
      recurrences of duodenal ulcer following vagotomy (I)].
AB  - Results of the computer processing of the electron base of data of 1706 patients
      with duodenal ulcer are presented. The data base includes the pre- and
      postoperative findings of comprehensive clinical instrumental examinations of the
      patients. Special attention in the work was given to the diagnostic and
      prognostic significance of the gastric secretion parameters before operation (the
      nocturnal secretion. Key test). The main conclusion of the study is that the well
      known prognostic criteria of the appearance of recurrent ulcers after vagotomy,
      based upon the findings of clinical instrumental examinations, the parameters of
      the acid gastric secretion included, are not sufficient. The level of acidity of
      the gastric juice in each patient is considered as a genetically fixed sign.

PMID- 9235763
TI  - [The role of endoscopy in determining the indications for the surgical treatment
      of the Mallory-Weiss syndrome and of bleeding acute gastroduodenal ulcers].
AB  - The frequency of acute sources of bleeding has recently increased (47%) in the
      general picture of gastrointestinal bleedings which makes the improvement of
      diagnosing "acute" sources of hemorrhage and the development of more perfect
      methods of nonoperative hemostasis very actual. The authors believe that
      "Kaprofer" used in most of patients with bleedings from acute ulcers and ruptures
      of the gastro-esophageal zone mucosa (95%) allows the hemorrhage to be arrested.
      The treatment can be continued without operative interventions. Search for new
      hemostatic drugs must be performed in order to obtain reliable and long-term
      effects of drugs with a minimum aggressive action upon the mucosa.

PMID- 9235764
TI  - [The diagnosis and surgical procedure in tumorous obstruction of the left half of
      the colon].
AB  - An analysis of results of examinations and surgical treatment of obturative
      obstruction in 370 patients with stenosing tumor of the left half of the colon
      has been made. The patients age was from 28 to 88 years. Women--219, men--151. It
      was established that best immediate results were obtained after radical primary
      operations without a simultaneous reestablishment of the intestinal continuity.

PMID- 9235765
TI  - [A method for external painful stimulation in the treatment of arteriosclerosis
      obliterans of the vessels of the lower extremities].
AB  - Under analysis are results of treatment of 21 patients. Positive effects were
      obtained in 19 of them. This effect was noted in 6 patients during 2 years.

PMID- 9235766
TI  - [Distal shunting in critical ischemia of the lower extremities in patients
      younger and older than 80].
AB  - Under analysis are the factors of operative risk and results of operative
      interventions on distal segments of the arteries in elderly and senile patients
      with critical ischemia of lower extremities against the background of generalized
      atherosclerosis. Seventy-eight bypasses were fulfilled: ileo-femoral, femoro
      popliteal, femoro-tibial, femoro-fibular. Pain at rest and gangrene of the foot
      and toes tissue were considered to he indications to bypasses. Among the risk
      factors smoking and arterial hypertension are particularly stressed.
      Postoperative lethality in patients of 80 years of age and older was 12.5%, among
      the patients from 70 to 80 years of age--7.7%. The active strategy is believed by
      the authors to be justified for revascularization of the extremity distal
      segments in critical ischemia and threatening amputation in the patients of 80
      years of age and older.

PMID- 9235768
TI  - [The methodology for the objective assessment of trauma severity (I. The
      assessment of the severity of mechanical injuries)].
AB  - The article proposes the methodology for assessment of the trauma severity
      according to two parameters: the severity of injuries and the severity of the
      wounded's and victims' state. The severity of injuries is a morphological
      characteristic of the trauma and it is a stable parameter, while the severity of
      the state is a functional characteristic of the trauma and represents a dynamic
      parameter. The assessment of each parameter is based upon calculation of
      quantitative indices by original scales. The authors propose a scale "MFS-I(MT)"
      for the assessment of the mechanical injury severity. Its specific features are
      polycriterial and are of the universal character. The injuries are characterized
      by weighed indices of the severity according to 3 criteria: the probability of a
      lethal outcome permanent invalidism and continuous loss of the ability to work.
      The scale can be used for the assessment of isolated, multiple and combined
      traumas. It is intended for using in military field conditions and in extreme
      situations.

PMID- 9235767
TI  - [The principle of cytokine therapy in the sepsis syndrome (a preliminary
      report)].
AB  - The results of using recombinant interleukin-2 from yeast for the treatment of
      patients with the sepsis syndrome are discussed. It is noted that there was a
      marked immunomodulating effect, the amount of endogenous interleukin-2 increased.
      The patients' state was shown to become less severe (according to the SAPS
      criterion), the patients felt better. A conclusion is made of the possibility in
      principle and expediency of using cytokines for the treatment of patients with
      the sepsis syndrome.

PMID- 9235769
TI  - [The principles of the delivery of specialized surgical care in wounds of the
      heart].
AB  - The article presents results of treatment of 84 patients with wounds of the
      heart. Of great importance is to shorten the time from getting the injury to
      rendering specialized surgical aid. A wider volume of care at the prehospital
      stage is developed. The creation of a regional program of treatment of patients
      with chest wounds is thought to be expedient. Lethality was 13%. It was stressed
      that better results of treatment of patients with heart wounds was dependent not
      only on using the adequate diagnostic and medical methods but also on the
      improvement of organization of aid to such people.

PMID- 9235770
TI  - [Emergency computed tomography in closed trauma of the chest and abdomen].
AB  - An analysis of using computed tomography (CT) in 152 patients with closed traumas
      of the chest and abdomen has shown that CT is indicated in cases of disagreements
      between the clinical picture and findings of the laboratory instrumental methods
      of examination when injuries of organs and tissues and development of early and
      late complications are suspected. The resolution of CT in closed trauma of the
      chest was at an average 97.3%, in closed trauma of the abdomen 94.9%. The
      possibility to perform the emergency CT in patients with a severe combined injury
      of the chest and abdomen during 24 hs a day allows injuries of the aorta, central
      and subcapsular hematomas of the liver and spleen to be diagnosed in a short time
      as well as the exact character of injuries of the pancreas and kidneys. CT is
      thought to be the method of choice for diagnosis of injuries of organs of the
      mediastinum and retroperitoneal space.

PMID- 9235771
TI  - [The surgical procedure in trauma to the cervical spine].
AB  - The authors experience based upon the results of operative treatment of 148
      patients with injuries of the cervical spine and dysfunctions of the upper
      extremities was used in order in substantiate the volume of diagnostic measures,
      indications to different methods of operative treatment. The latter is considered
      to be expedient in all periods of the traumatic disease of the spinal cord with
      retained radicular-medullary compression.

PMID- 9235772
TI  - [The quality of life of children who have undergone emergency surgical operations
      in the neonatal period].
AB  - The investigation of 86 children at the remote period after operations for
      developmental defects in their neonatal period enabled the criteria of the
      successful medico-rehabilitative treatment to be determined according to the
      indicators of quality of their life. It was found that the quality of life of
      such children remained quite satisfactory even without systematic rehabilitation.
      At the same time, the critical periods were determined in the physical and mental
      development of the children and the pathology with which the child's
      rehabilitation could be slower and less effective.

PMID- 9235773
TI  - [Current problems of vascular surgery in childhood].
AB  - Under analysis are remote results of treatment of 751 children with congenital
      and acquired diseases of the vessels. Grounds are given for treatment of these
      diseases in the light of the classical syndromes of disturbed hemodynamics. The
      investigation of developmental and individual peculiarities of these syndromes is
      thought to be necessary. The leading role of microsurgical methods of treatment
      of such diseases of the vessels in children is stressed.

PMID- 9235774
TI  - [The history of the surgery of esophageal atresia (based on data from the Saint
      Petersburg Center for Neonatal Surgery)].
AB  - The article presents 42-year experiences with surgical treatment of atresia of
      the esophagus in 814 neonatals in the St. Petersburg Center of surgery in
      neonatals. Under analysis are the consecutive periods of work in this field,
      development and introduction into practice of the methods of surgical
      interventions, the original Bairov's operation--double esophagostomy--included.
      Factors responsible for results of the treatment of esophageal atresia are
      described. Improvement of the methods of treatment has resulted in a possibility
      mainly to make anastomoses of the esophagus and reduce lethality of neonatals
      with esophageal atresia from 81 to 7.7%.

PMID- 9235775
TI  - [Reconstructive plastic surgery of the esophagus in children].
AB  - The article presents the authors' experiences with reconstructive-plastic
      operations of the esophagus in children. The esophagoplasty was performed in 60
      patients with congenital and acquired diseases. Among the congenital diseases are
      esophageal atresia, short esophagus and Barrett's esophagus, the acquired
      diseases include postburn scarry injuries. The optimum method of creation of the
      artificial esophagus are described. Of great significance are thought to be
      angiosurgical and microsurgical methods of cutting out the intestinal
      transplants. Cases of free autotransplantation of the intestinal segments for the
      substitution of the injured esophagus are described. Positive results were
      obtained in most cases.

PMID- 9235777
TI  - [The surgical treatment of vesicoureteral reflux in kidney duplication in
      children].
AB  - The examination of 41 patients with a complete renal duplication and
      vesicoureteral reflux (VUR) into 57 ureters has shown a direct dependence of
      morphological immaturity of the parenchyma of the double kidney segment and
      functional insufficiency of the obturative apparatus of the ostium of the
      corresponding ureter on the degree of its dislocation corresponding to the normal
      localization on the inner surface of the urinary bladder. For patients with
      marked lateral position of the main ostium of the organ saving operations are
      senseless because of high degree of VUR and deep dysplasia of the renal tissue.
      In cases with moderate lateralization of the ureter ostium it is expedient to
      fulfil such antireflux interventions as Lich-Gregoir operations in a "single
      block" or the endoscopic correction of the ostium with a synthetic medical
      siloxan rubber or polyacrylamide gel "Interfall".

PMID- 9235776
TI  - [The classification and choice of the method of treatment in fecal incontinence
      in children].
AB  - Complex examinations of 682 children with fecal incontinence including the
      colonodynamic investigation, computed tomography of the pelvis and endorectal
      sonography have shown that disturbance of the reservoir function and defecation
      urge mainly take place in cases of functional disorders. Anal incontinence of an
      organic type can also arise without an injury of the sphincter apparatus as a
      result of prolapse of the mucose membrane or stenosis of the distal portion of
      the rectum. In such cases the operative treatment is indicated. In patients with
      the incompetent internal and partially injured external sphincter treatment
      should be started by conservative measures. When the function of the pubo-rectal
      muscle or of all the elements of the closing apparatus is disturbed the operative
      treatment is indicated. The operative correction is possible for neurogenic
      incontinence in order to create the ano-rectal angle. A classification of anal
      incontinence in children is proposed which takes into account the etiology,
      pathogenesis and allows the optimum treatments to be chosen.

PMID- 9235778
TI  - [Vladimir Andreevich Oppel' (1872-1932)].

PMID- 9235779
TI  - [The surgical treatment of disorders in the formation and fusion of the lumbar
      vertebrae in children].
AB  - The observations of 61 children with congenital scoliosis and kyphoscoliosis
      during the period from 6 months till 7 years of age allowed the prognostically
      unfavourable signs of progressing the deformation to be determined. Radical
      operations are recommended for elimination of the defect and correction of the
      deformation at the age less than 4 years. Stabilization of the area of the defect
      is thought to be enough when it is localized in the lumbosacral zone. Early
      interventions give hope for the self-correction of the sacrum and pelvis due to
      rearrangement of the child's sacrum.

PMID- 9235780
TI  - [Current problems in the reconstructive surgery of the locomotor apparatus in
      children].
AB  - The authors analyze results of treatment of 778 children with malignant and
      benign tumors of the bones, pseudoarthroses, amputations of lower extremities and
      fingers, injuries of the tendons, vessels and contused-lacerated wounds of distal
      phalanges of fingers. The possibility to use a precision technique for the
      reconstructive operations of the vessels in children is shown.

PMID- 9235781
TI  - [The characteristics of the anesthesiological support for surgical interventions
      in patients earlier operated on the heart].
AB  - The article presents an analysis of the authors' experiences with
      anesthesiological maintenance of operations on patients after revascularization
      of the myocardium, implantation of permanent cardiostimulant and heart value
      prosthesis. Main risk factors responsible for severe complications were found to
      be congestive heart failure, myocardial infarction which took place 6 months
      before the operation, certain forms of arrhythmias, unstable stenocardia,
      pronounced stenosis of the aortic valve, age older than 70 years, diabetes
      mellitus. The comprehensive preoperative preparing, choice of the adequate
      methods of anesthesia and maintenance of the up-to-date intraoperative monitoring
      create the conditions for a less risk of the surgical treatment.

PMID- 9235782
TI  - [The personality of soldiers with inappropriate behavior patterns at the end of
      military service].
AB  - The end of military service is the turning point in young man's life. After the
      organized way of living in military environment, he is expected to enter the
      regular life duties for which he is not prepared to. The aim of this
      investigation was to study the basic features of soldier's personality that
      contribute to the maladapted behavioral patterns in frustrating situations
      occurring at the end of military service, as well as the close inspection of the
      behavioural changes in such persons, which occurred in that period. Thirty-three
      soldiers who came to the neuropsychiatric examination between the 10th and 12th
      month of compulsory military service (72.72% for the first time since joining the
      Army) were examined. The soldier's personality in EPI (Emotion Profile Index)
      test was characterized by: lower incorporation and reproduction, but raised level
      of destructiveness and aggressiveness. The graphic representation of personality
      profile in the circle of segment values demonstrates the similarity of
      structurality level to the average profile of emotionally immature person and in
      certain segments to the persons who attempted suicide. Manifested behavioural
      patterns in soldiers had the features of Short timer's syndrome. The results of
      our investigation have shown that the problems of maladapted behaviour in
      soldiers at the end of military service are dominantly associated with the poor
      personality integration preexisting chronic problems of the immediate family and
      differing starting positions after the discharge as well as the poorer
      organization of living and work of soldiers in the unit due to the inadequate
      leadership.

PMID- 9235783
TI  - [Amyotrophic lateral sclerosis in a defined population in Belgrade--an
      epidemiologic study].
AB  - The paper shows the results of the first epidemiological study of ALS in
      Belgrade. The incidence, prevalence and natural course of ALS were determined for
      the period 1985 through 1991. The distribution of 58 newly discovered cases in a
      7-year survey period showed that the average annual incidence rate was 0.54 per
      100000 population (95% confidence interval, 0.23-1.06), and age-adjusted
      incidence rate was 0.42 per 100000 population (95% confidence interval, 0.18
      0.83). The rate for males was 1.5 times higher than the rate for females. The
      greatest age-specific average incidence rate was observed in patients between 60
      and 64 (3.66 per 100000 population: 95% confidence interval, 2.17-5.78). The
      actual age-adjusted prevalence rate on December 31, 1991 was 1.07 per 100000 (95%
      confidence interval, 0.71-1.71). The mean age at the onset of the disease was
      56.2 +/- 9.8 and it ranged from 24 to 74. The average interval between the onset
      of symptoms and the establishing of the diagnosis was 14.38 +/- 17.26 months. The
      mean duration of the disease was 27.7 +/- 18.2 months. The cumulative probability
      of survival was 27% for the whole population in a 5-year interval. Elderly
      patients and those with bulbar signs at the onset had a poorer prognosis.

PMID- 9235784
TI  - [Comparative analysis of agreement between cytologic diagnosis by examination of
      tissue imprints and pathohistologic findings in intraoperative breast biopsy].
AB  - In 34 benign and in 31 of malignant breast tumors, the touch preparations
      (imprints) were made concomittantly with frozen sections. In the comparison with
      the pathohistological findings, there were neither false positive nor false
      negative cytologic diagnoses. In three cases of benign breast tumors and in one
      carcinoma, the number of cells in imprints was not sufficient for cytologic
      diagnosis. The cytologic and pathohistologic diagnoses were in accordance in
      98.8% of benign breast tumors and in 100% of carcinomas.

PMID- 9235785
TI  - [Contact thermometry of lesions in alopecia areata].
AB  - The contact thermometry has been performed at the center of lesions, at the
      periphery and at the adjoining healthy skin in 10 patients with alopecia areata
      (AA) of the scalp. The lowest temperature was recorded in the center of lesions
      (approximately 33.55 degrees C), slightly higher in the periphery (approximately
      33.71 degrees C) and the highest in the adjoining healthy skin (approximately
      34.01 degrees C). The authors suggest the skin temperature to be the result of
      the degree of vascularization. The obtained results were examined in reference to
      the results published elsewhere on the light and electronic microscopy of AA
      lesions where the changes in capillaries were found. Based on all the above, the
      authors consider the topical use of drugs that improve the peripheral circulation
      to be justified in the treatment of AA.

PMID- 9235786
TI  - [Writing scientific articles--practical advice].

PMID- 9235787
TI  - [New possibilities in the treatment of autoimmune diseases].

PMID- 9235788
TI  - [A rational approach in diagnosis of otosclerosis].

PMID- 9235789
TI  - [Post-traumatic arteriovenous fistulae and pseudoaneurysms].
AB  - The surgical treatment of 13 posttraumatic arteriovenous (AV) fistulae and 32
      pseudoaneurysmae (PsAn) treated in the last 5 years in the Center of vascular
      surgery of the institute of cardiovascular diseases, Clinical center of Serbia
      (Belgrade) was presented. Three women and 42 men (mean age 31.7 years) were
      examined. Twenty-one injuries occurred in a war, while 24 injuries occurred in
      the peacetime. In most of the cases the superficial femoral artery was involved.
      The average time elapsed from the moment of injury till surgery, was 9 months in
      patients suffering from AV fistulae, while in patients suffering from PsAn the
      elapsed time was one month. In all of those with AV fistulae, some
      reconstructions of artery and vein were performed, except in 2 cases where the
      vein was ligated. In twenty-six patients suffering from PsAn the arterial
      reconstruction was performed, while in 6 cases the artery was ligated.
      Considering the type of artery, none of the patients suffered from postoperative
      ischemia. Patients were followed up for 2 years and 2 months on the average after
      the operation. As far as the reconstructive operations were concerned,
      postoperative patency rate was 100%, while limb salvage was achieved in 96.9%.
      Namely, one amputation was done in spite of high arterial patency rate, but it
      was indicated by massive bone-muscle tissue loss, that occurred after an injury
      by the land-mine. Due to the rapid progress of the disease the authors suggested
      that the operative treatment of posttraumatic AV fistulae and PsAn should start
      as soon as possible. This was supported by good follow-up results in operatively
      treated patients.

PMID- 9235790
TI  - [Molecular approach in the current understanding of the onset and development of
      atherosclerosis].

PMID- 9235791
TI  - [Neuroradiologic diagnosis of caudal radiculopathy].

PMID- 9235792
TI  - [Ulcus molle].

PMID- 9235793
TI  - [Forms of drugs in ancient cultures: preparation and development].

PMID- 9235794
TI  - Current Perspectives in Acid Inhibitory Therapy. Proceedings of a meeting. New
      Haven, Connecticut, November 17-19, 1995.

PMID- 9235795
TI  - [Pathophysiological mechanisms of the renin-angiotensin system and its
      pharmacologic modification by ACE inhibitors or angiotensin II (type 1) receptor
      blockers in cardiovascular diseases].
AB  - As a net effect of ACE-inhibitors and AT1-receptor antagonists on the renin
      angiotensin system (RAS) cardioprotection due to vasodilative (reduction of blood
      pressure, afterload reduction), antiproliferative (reduced cell growth, reduction
      of "vascular" and/or "ventricular remodeling", reduced formation of extracellular
      matrix), as well as antiadrenergic actions and due to the stimulating effect on
      natriuresis, reduction of blood pressure, preload reduction can be expected.
      These aims of therapy have mostly been confirmed for the action of ACE-inhibitors
      by experimental and clinical studies but except for the treatment of arterial
      hypertension and few preliminary reports concerning the treatment of cardiac
      dysfunction, no comparable data are available for AT1-receptor antagonists. To
      date, an antithrombotic and profibrinolytic action could only be demonstrated for
      ACE-inhibitors. This effect has been discussed to be responsible for the
      improvement of long-term prognosis in patients with coronary artery disease.
      Despite the similar spectrum of action there exist important differences between
      ACE-inhibitors and AT1-receptor antagonists that might underline the need of an
      individual use of these drugs: the dual action of ACE-inhibitors on the RAS and
      the kinin system bears many benefits but has been also shown to be accompanied by
      side-effects, mainly chronic dry cough, in a relatively high percentage of
      patients thus leading to discontinuation of therapy in 8-14%. This respective
      side-effect can be prevented by the use of AT1-receptor antagonists. It has been
      discussed whether the incomplete action of ACE-inhibitors on AT1-receptor
      mediated effects is at least in part responsible for the efficacy of this drug
      which is relatively high (75-80%) as compared to other substances. Due to their
      direct action, AT1-receptor-blockers might also be of high effectiveness for the
      treatment of severe heart failure. A combination of the ACE-inhibitor-mediated
      activation of the kinin-system with the more specific blockade of AT1-receptors
      by AT1-receptor antagonists might be of benefit and is currently under
      investigation. Finally, it has been discussed that the increased AT II
      concentration in case of AT1-receptor-blockade activates AT2-receptor-mediated
      mechanisms thus leading to an additive vasoprotective effect.

PMID- 9235796
TI  - [Arterial hypertension and blood pressure profile in patients with Williams
      Beuren syndrome].
AB  - The prevalence of hypertension and the diurnal blood pressure pattern were
      investigated in patients with Williams-Beuren syndrome (WBS) by blood pressure
      measurements in 142 children, adolescents, and young adults (female n = 62, male
      n = 80; median age 6.5 years (0.1-34.3 years)) and evaluation of ambulatory blood
      pressure data from 45 patients (female n = 21, male n = 24; median age 7.8 years
      (1-23.8 years)). Measurements revealed systolic hypertension in 46.5% of 142
      patients, diastolic hypertension occurred in 36.6% (i.e. actual pressure > 95
      percentile). According to the ambulatory data 42.2% of 45 patients had
      hypertension (mean arterial pressure > normal + 2SD). The nocturnal decline of
      the blood pressure was normal in hypertensive patients but reduced in
      normotensives (p < 0.01 vs normals). Males were more often hypertensive than
      females (46% vs 38%). Hypertensives had a higher body mass index than
      normotensives (19.5 vs 16.6 kg/m2, p < 0.05). In normo- and hypertensive WBS
      patients mean heart rates were elevated during day- and nighttime (p < 0.02 vs
      normals) the latter due to a reduced nocturnal decline. The prevalence of
      hypertension in WBS patients amounts to about 40%, thus being four- to eight-fold
      in comparison to healthy young adults or children. The diurnal blood pressure
      pattern and the elevated heart rates indicate that an increased arterial
      stiffness due to the vascular disease in the WBS and augmented sympathetic
      activity might play a role in the genesis of hypertension. Thus, effective
      antihypertensive treatment is likely to become difficult. From our experience
      beta-blocking agents are often successful in hypertensive WBS patients.

PMID- 9235797
TI  - [Estimation of radiation exposure and radiation risk for employees of a heart
      catheterization laboratory].
AB  - The staff at interventional radiological procedures is exposed to high levels of
      ionizing radiation. This applies especially to measures at cardiac
      catheterization laboratories. In this study the annual radiation exposure to the
      staff was estimated by measuring the dose rate under characteristic conditions.
      It could be shown that the resulting radiation exposure was strongly dependent on
      the radiation protection measures and is also dependent on the operation
      conditions of the x-ray-tube. The effective dose for the physician wearing a lead
      apron and thyroid shield was determined to about 1.7 mSv/a. Without a thyroid
      shield an effective dose of about 3.5 mSv/a resulted. This corresponds to
      approximately the natural background radiation of about 2.4 mSv/a in the Federal
      Republic of Germany. From the number of procedures performed we could derive an
      effective dose of approximately 1-2 microSv per application for the physician,
      averaged over all types of procedures. Further, it could be shown that the
      readings of the film badges, usually worn by the staff, underestimate the
      effective dose by approximately a factor of two. This is because the film badges
      do not include the contribution of the unshielded parts of the body to effective
      dose. From the estimated annual effective dose, a lifetime dose of 68 mSv was
      estimated for a 40-year working career. The corresponding lifetime risk for
      induced fatal cancer due to radiation exposure was determined to 0.3% applying
      the ICRP risk factor of 4 x 10(-2) Sv-1. Considering the NCRP recommendations for
      a safe occupation, working in a cardiac catheterization laboratory can be
      considered as safe when applying all radiation protection measures. However,
      changing the protection measures and modifying the parameters of the x-ray-tube
      can lead to strong changes of the radiation exposure and the resulting risk
      estimation.

PMID- 9235798
TI  - [Incidence and therapy of peripheral arterial vascular complications after heart
      catheter examinations].
AB  - We analyzed the incidence and management of major vascular complications at the
      arterial puncture site following diagnostic or interventional cardiac
      catheterization. 27387 cardiac catheterization procedures were performed for
      diagnostic (n = 19581) or interventional (n = 7806) purposes at our institution
      during a 7-year study period. A total number of 114 major vascular complications
      (0.42%) were identified. In 36 (0.13%) patients an arterial occlusion at the
      puncture site was detected, 34 patients (0.12%) had severe hematoma (blood
      transfusion or surgical repair necessary), 32 patients (0.12%) developed false
      aneurysms, 9 patients (0.03%) with av-fistulas and 3 patients (0.01%) had other
      complications. The following factors were predictive for a significant increase
      in the incidence of major vascular complications: Female gender, interventional
      catheterization using larger introducer sheaths and necessitating effective
      perioperative doses of heparine, and peripheral vascular disease. Operative
      repair was necessary in 62 patients (54%), 34 patients (30%) were treated
      conservatively. In 18 patients (17%) acute vascular occlusion could be managed by
      percutaneous transluminal balloon dilatation and intravascular thrombolysis of
      the obstruction, in 3 patients additional stent-implantation was necessary in the
      presence of a large occlusive dissection. Overall the rate of clinically
      significant major vascular complications is low. In the future a greater number
      of vascular complications at the entry site for cardiac catheterization will be
      treated with nonoperative methods (e.g. manual compression of pseudoaneurysms or
      catheter-based techniques for recanalization of acutely occluded vessels.

PMID- 9235800
TI  - [Evaluation of secondary prevention of coronary heart disease. Results of the
      EUROSPIRE study in the Munster region].
AB  - BACKGROUND: New recommendations for secondary prevention of coronary heart
      disease (CHD) were issued by the European Society of Cardiology (ESC), the
      European Atherosclerosis Society (EAS) and the European Society of Hypertension
      (ESH) in 1994. The main objective of the EUROASPIRE study (European Action on
      Secondary Prevention by Intervention to Reduce Events) was to evaluate to what
      degree the new recommendations have been implemented and whether a significant
      risk factor reduction in patients who presented with CHD has been achieved. The
      present study was conducted in the region of Munster, Westphalia, Germany, as
      part of the nine-country EUROASPIRE study. METHODS: A total of 524 patients (58.6
      +/- 8.2 years) were included in the study by abstracting data from their medical
      records. According to the clinical event which led to admission to the hospital,
      patients belonged to the following four groups: 1) coronary artery bypass graft
      (CABG), 2) percutaneous transluminal coronary angioplasty (PTCA), 3) acute
      myocardial infarction, 4) acute myocardial ischemia. Initially, a pre-specified
      number of patients had been recruited with the goal of having 100 patients in
      each of the four groups participate in the follow-up interview and examination.
      At least 6 months and, on average, 20 months after hospital discharge for the
      acute event, 74.8% of the patients came to an interview and examination for an
      evaluation of their risk profile. RESULTS: At the interview, 15.6% of the
      patients smoked, 22.7% were obese, 54.6% had blood pressure levels above 140/90
      mm Hg and 31.3% a total cholesterol/HDL-cholesterol-ratio greater than 5. Risk
      factor modification over time was insufficient as only one-fifth of patients had
      values of their risk factors within the target range at the time of the
      interview. CONCLUSION: The goals of secondary prevention have not been achieved
      in the region of Munster-there is clearly room for improvement. Considering the
      treatment of patients with CHD, the recommended strategies of secondary
      prevention need to be applied more intensively in clinical practice.

PMID- 9235799
TI  - [Early treatment of acute myocardial infarct: implementation of therapy
      guidelines in routine clinical practice, MITRA pilot phase].
AB  - The prognostic value of thrombolytics, aspirin, beta-blockers and ACE-inhibitors
      has been well documented in large clinical trials, but the application of these
      drugs in clinical practice is not known. MITRA is a multicenter study of 54
      hospitals in a defined region in southwest Germany. The aim is to document actual
      clinical practice (pilot phase) and to establish an individually optimised
      prognostic therapy for acute myocardial infarction, considering only the absolute
      contraindications for each drug. In the pilot phase, 1303 consecutive patients
      with acute transmural myocardial infarction were enrolled. The median age was 66
      years, the prehospital time was 2.7 hours. 47% had an anterior infarction. In the
      subgroup of patients without absolute contraindications, only 53.4% were treated
      with thrombolytics, 87.6% with aspirin, 37.1% with beta-blocker, and 17.4% with
      ACE-inhibitor. Out of these, patients were classified as "optimally treated" if
      they received thrombolysis, aspirin as well as beta-blocker. Patients were also
      included if any of these medications was withheld in the presence of absolute
      contraindications. Treatment was defined suboptimal, if the patients did not
      receive any of these three medications despite the absence of absolute
      contraindications. Only 29% (n = 383) received an optimal post-infarction therapy
      and 71% (n = 775) a suboptimal treatment. The univariate analysis revealed 10
      variables influencing optimal therapy. In this subgroup patients were younger,
      they more often had clear ECG-findings or left bundle branch block, an anterior
      infarction, acute cardiac failure, AV-block, bradycardia, recent trauma or
      surgery (less then 2 weeks) and a severe chronic obstructive lung disease. The
      prehospital time was more often available. Early mortality after 2 days was 5.0%
      versus 9.3% in the suboptimal treated patients (OR: 0.5, CI: 0.30-0.86) the total
      inhospital mortality was 10.9% in the optimal versus 17.7% in the suboptimal
      group (OR: 0.6, CI: 0.38-0.84). In a multivariate analysis the parameter "optimal
      treatment" was found to be an independent predictor of the early (OR = 0.4; CI:
      0.20-0.69) and the inhospital mortality (OR = 0.4; CI: 0.25-0.64). The following
      in-hospital events occurred: stroke 2.8%, reinfarction 12.9%, cardiac failure
      21.5%, cardiogenic shock 10.4% and in-hospital mortality 18.1% (2-days mortality
      9.5%). Pharmacological therapy for acute myocardial infarction is inconsistent
      with the recommendations suggested in recent clinical trials and needs to be
      individually optimised. Optimal treatment is an independent predictor of early
      and inhospital mortality.

PMID- 9235801
TI  - [Endomyocardial biopsy--helpful in differential diagnosis between myocarditis and
      dilated cardiomyopathy. A case report].
AB  - Endomyocardial biopsy is an established technique to distinguish between
      myocarditis and dilated cardiomyopathy. Even when clinical symptoms for
      myocarditis are lacking, immunohistologic findings may establish a clear
      diagnosis. For treatment, however, an early diagnosis is mandatory. We report on
      a 44 year old patient who was admitted with the echocardiographic diagnosis of
      dilated cardiomyopathy. He underwent diagnostic angiocardiography and
      endomyocardial biopsy. The latter demonstrated an active myocarditis. At the time
      of read-mission, 2 weeks later, the patient had deteriorated. Now, additional to
      a symptomatic therapy, prednisolone, azathioprine and human immunoglobulin G were
      given and patient conditions improved dramatically. The use of endomyocardial
      biopsy seems recommendable in order to define patients diagnosis and their
      results may be necessary to decide patients therapy.

PMID- 9235802
TI  - [Immunosuppressive therapy for effective suppression of life threatening
      ventricular tachyarrhythmias in chronic myocarditis].
AB  - Chronic myocarditis predisposes to the occurrence of spontaneous ventricular
      arrhythmias. It is not known if an immunosuppressive treatment-as a casual
      therapy-leads to arrhythmia suppression. In the present study, 12 patients (four
      female, eight male, mean age 53 +/- 15 years) with a mean left-ventricular
      ejection fraction of 52 +/- 19% were included. After exclusion of coronary
      macroangiopathy, the presence of chronic myocarditis was demonstrated by
      immunohistological evaluation of right-ventricular biopsies taking the number of
      specific lymphocytes (CD 2-8), of activated macrophages and the degree of HLA
      expression on interstitial and endothelial cells as a basis. Seven patients had a
      successful resuscitation due to ventricular fibrillation in their case history,
      three patients presented sustained monomorphic ventricular tachycardia and two
      syncopes with inducible tachyarrhythmias. As a "conventional" therapy ten
      patients received antiarrhythmic drugs and four patients an implantable
      cardioverter/defibrillator. After confirmation of the diagnosis by a second
      biopsy after 3 months, all patients underwent an immunosuppressive therapy with
      methylprednisolone. The initial dose of 1 mg/kg body weight was reduced by 20 mg
      each every 2 weeks, until a maintenance dosage of 8-12 mg/day was achieved. If
      the control study after 6 months still gave a positive result, a combined therapy
      with azathioprine, 100-150 mg/day, was carried out for a further 6 months. In
      nine patients (75%), the control biopsy became negative, in three patients (25%),
      the biopsy remained to be positive. In the group presenting negative biopsies, no
      tachyarrhythmia relapse occurred within a follow-up period of 49 +/- 13 months,
      while in the group with positive biopsies, relapses occurred in two of three
      patients. Complete suppression during EPS after therapy was achieved in 50% of
      the patients who were inducible before therapy. In addition to lymphocyte
      infiltration, particularly HLA expression on endothelial and interstitial cells
      was significantly reduced; left-ventricular ejection fraction was improved only
      in tendency, while left-ventricular filling pressure decreased significantly. In
      summary, in patients with chronic myocarditis and malignant ventricular
      arrhythmias, a high-dose immunosuppressive long-term therapy results in the
      significant reduction of inflammatory infiltrations in about 75% of the cases
      and, at the same time, in the effective suppression of arrhythmias.

PMID- 9235803
TI  - [Scientists of the countries of the basin of the Sea of Japan (Japan-Russia-China
      Korea) discuss the fundamental problems of the brain and epilepsy (Rim Japanese
      Sea Symposium: "Shining a light on epilepsy", Japan, Yonago; November 15-17,
      1996)].

PMID- 9235804
TI  - [The importance of integral approaches in the search for predictors and in the
      study of the mechanisms of the occurrence and development of epilepsy].
AB  - The peculiarities are described of brain electric activity of inbred mice and
      rats susceptible and resistant to epileptogenic influence. The EEG are discussed
      of anti- and proconvulsant drugs in man and animal models. Brain weight and
      dermatoglyphic patterns are suggested as predictors of epilepsy development.

PMID- 9235805
TI  - [The neuropeptide galanin and the seizure reactions of the developing brain].
AB  - In this work polyfunctional peripheral (pancreas) and central effects of galanin
      1-29 (gal.) were reviewed. In hypothalamus gal. exerts neuroendocrine effects
      through modulation of secretion of principal hormones of hypophysis, co-localized
      with acetylcholine in some brain structures including hippocampus. Gal.
      influences behaviour and memory. Newest hypotheses of T. Hokfelt and J. N.
      Crawely [correction of G. Crowly] on the involvement of gal. to pathogenesis of
      in Alzheimer disease and possibilities of its clinical antiamnestic utility are
      discussed. Our own data indicates antiseizure effect of gal. in the model of
      febrile convulsions in children--hyperthermia induced seizures in neonatal rats
      in the age from 5 to 13 days. Systemic intraperitoneal administration of gal. was
      effective in certain age--7-11 days of postnatal period--in preventing
      hyperthermia induced seizures: in increased by 2-3 times latency of minimal
      seizures and clonic-tonic generalized seizures. In adults rats gal. showed
      antiseizure action when administered intranasal in the model of pentilenetetrazol
      seizures (modified test with repeated administration of subthreshold doses).
      Modern data on structure and function of galanin, its chimeric analogs and
      galanin receptors receptors are discussed.

PMID- 9235806
TI  - [The morphofunctional characteristics of the neurons and their connections in the
      neocortex of man and animals].
AB  - The current paper summarizes the classical ideas on synaptic links in intracortex
      isofunctional types of cells, based on the results of the Golgi method. In
      addition, it discusses data of modern research on structural-functional
      organization of the neocortex module of man and of animals.

PMID- 9235807
TI  - [The motor innervation of the axial skeletal musculature in vertebrates].
AB  - The principles of innervation and evolution of axial (body) skeletal musculature-
      from primitive chordata to higher mammalians--are briefly considered. The
      literature and original data of author are analysed, demonstrating specific
      pattern of neural control and peripheral motor innervation of axial musculature,
      differing from that in limb muscles of vertebrates. A special notice is taken in
      viewing the phenomenon of dual innervation of several fast axial muscles, which
      has been recently discovered in different groups of lower (water) and higher
      vertebrates. The hypotheses are considered, explaining the possible origin and
      significance of dual innervation, as well as the role of two different pools of
      motoneurons realizing the dual innervation of vertebrates fast axial muscles.

PMID- 9235808
TI  - [Magnesium salts in physiology and pathology: the potentials for their use in
      medicine].
AB  - This review carries literary data on a biological effect, physiological and
      pathophysiological significance of magnesium ions for the organism. Diseases of
      hypo- and hypermagnesemia and mechanisms of regulation of magnesium content in
      the organism are reviewed in the article. There are cited data on the use of
      preparations, containing magnesium ions in pathologies of the kidneys, liver,
      gastrointestinal tract; in diabetes mellitus, arrhythmias, hypertensions,
      ischemias, myocardial infarction and other conditions. There are review data on
      the use of magnesium-containing mineral bishofit, preparations and balneologic
      agents on its basis.

PMID- 9235809
TI  - [A comparative analysis of the existing standards for exposure to ultraviolet
      radiation].
AB  - Quantitative analysis of threshold limit levels of UV-irradiation in the workroom
      environment established in USA, Netherlands and Russia was made. Comparison of
      its results with modern information about effective doses and action spectra of
      UV-radiation biological action allowed to reveal essential differences in the
      approach to rate setting and in some cases presence of internal contradictions
      and exceeding of threshold limit levels of UV irradiation above biologically
      effective values. The possibility of workroom UV standards utilisation for
      regulation of nature UV-radiation exposures was considered.

PMID- 9235810
TI  - [Detection of dsDNA antibodies in diagnosis of systemic lupus erythematosus-
      comparative studies of diagnostic effectiveness of 3 ELISA methods with different
      antigens and a Crithidia luciliae immunofluorescence test].
AB  - Antibodies to double-stranded DNA (anti-dsDNA, dsDNA-Ab) are frequently found in
      systemic lupus erythematosus (SLE), especially during active disease and differ
      with respect to immunoglobulin class and avidity. The detection of anti-dsDNA is
      one of the diagnostic criteria for SLE according to the American College of
      Rheumatology (ACR). Most of the commercial ELISA test systems have great
      advantages in routine laboratory testing but often detect dsDNA-Ab which are not
      specific for SLE and therefore give false positive results for non-SLE patients.
      The newly developed ELISA presented here, using human recombinant dsDNA (h-Rek)
      is compared to two commercial ELISA tests with genomic dsDNA from salmon testes
      (L-dsDNA) or plasmid dsDNA (P-dsDNA) and to the Chrithidia luciliae
      immunofluorescence test (CLIF) as well. In this study 143 sera were tested, 48
      derived from patients with SLE, 40 from rheumatoid arthritis patients, 26 from
      non-rheumatoid patients whose sera were ANA-negative but L-dsDNA-Ab-positive and
      30 from healthy volunteers. All patients were followed and clinically defined by
      the rheumatology outpatient clinic of our hospital. The prevalence for SLE of all
      sera was 32%. The sensitivity was 0.73 (h-Rek), 0.83 (L-dsDNA), 0.81 (P-dsDNA)
      and 0.57 (CLIF); specificity was determined 0.84 (h-Rek), 0.62 (L-dsDNA), 0.63 (P
      dsDNA) and 0.98 (CLIF). The diagnostic efficiency of the L-dsDNA- and P-dsDNA
      assay was identical, 0.69, and amounted to 0.81 for the h-Rek and 0.84 for the
      CLIF. Comparing all the ELISA tests and CLIF, the human recombinant dsDNA ELISA
      is much more sensitive than the CLIF, but considerably more specific than the
      ELISA assays using genomic or plasmid DNA, whereas the diagnostic efficiency is
      very close to that of the CLIF. This new generation of anti-dsDNA ELISA using
      human recombinant dsDNA seems to be a much better diagnostic tool for the
      detection of highly specific anti-dsDNA antibodies in the diagnosis of SLE than
      other commercial ELISAs. These results can only be explained by the use of a
      human recombinant antigen instead of undefined genomic or recombinant plasmid DNA
      for immobilization.

PMID- 9235811
TI  - [RA-specific autoantibodies against a 68k antigen].
AB  - Despite commonly applied clinical criteria, the early diagnosis of rheumatoid
      arthritis (RA) often remains difficult, thus delaying on suitable early
      treatment. In search for a test furthering the early and reliable diagnosis of
      RA, we have screened for novel disease specific autoantibodies. To this end
      proteins were isolated from synovial membranes and other tissues following a
      special protein purification protocol, and these were separated
      electrophoretically. Western blots were then used to screen sera of RA patients
      and of individuals suffering from other rheumatic diseases for antibodies to any
      of these proteins. The most prominent RA specific immunoreaction was with a 68k
      antigen, occurring in 110 of 167 RA patients (sensitivity is 66%). The antibody
      could also be identified in seronegative RA patients but not in healthy
      individuals (55 tested), in only 1 SLE patient of a group of 98 patients with
      other rheumatic diseases and in 1 out of 22 HIV patients, resulting in a
      specificity of 99%. Moreover, the anti-68k antibody could be correlated with a
      more severe course of RA. 13 out of 20 anti-68k positive RA patients (58%) had
      subcutaneous nodules, while only 2 out of 11 anti-68k negative (20%) did. The
      mean sedimentation rate of these antibody positive patients was 51 mm/h and 26
      mm/h for the negative respectively. The 68k antigen was shown to be present in
      all human tissues investigated and is probably ubiquitously expressed. It is
      either located in the endoplasmatic reticulum or cytoplasm or both. Its
      isoelectric point is 5.1. It proved to be O-glycosylated and contains only one or
      a few sugar residues as the untreated and the deglycosylated antigen identical
      electrophoretical mobilities. The patient derived anti-68k antibodies were
      directed against the sugar residue: deglycosylation of the antigen completely
      abolished its immunoreactivity. N-acetylglucosamine competes with the antibody
      for binding the 68k antigen. The antigen physicochemical data of the 68k antigen
      argue against identity with one of the autoantigens in this molecular mass range
      already known to be associated with RA or other autoimmune diseases. It is
      neither identical to the 62k human antigen (EBNA-1) nor to RA33 (A2hnRNP), the
      50k Sa antigen or the Hsp70 class of heats-hock proteins. It is argued that the
      particular method of protein purification applied in combination with separation
      via SDS-PAGE in the presence of urea, made it possible to detect a hitherto
      unidentified antigen. Considering the striking disease specificity of the anti
      68k antibody it is now worthwhile to look for corresponding autoreactive T cells
      in order to analyse its role in the pathogenesis of RA.

PMID- 9235813
TI  - [Comparative endoscopic study of gastroduodenal tolerance of piroxicam-beta
      cyclodextrin vs piroxicam].
AB  - The gastroduodenal tolerability of piroxicam-beta-cyclodextrine was evaluated in
      a double-blind, parallel group study in 32 healthy male volunteers. The doses
      used were 20 mg piroxicam-beta-cyclodextrin vs 20 mg piroxicam daily over a
      period of 14 days. Gastric tolerability was assessed by using upper endoscopy.
      Gastroscopy was performed at base-line and after the dosing period of 14 days.
      The mucosal lesions were scored using modified Lanza criteria. In comparison to
      piroxicam, piroxicam-beta-cyclodextrine was significantly better tolerated after
      a 14 day dosing period. Mean gastric-duodenal score: Piroxicam-beta-cyclodextrine
      3 +/- 4 (median 1), piroxicam 6 +/- 4 (median 8). The score values for the
      stomach were for piroxicam-beta-cyclodextrin 2 +/- 3 (median 1) and for piroxicam
      4 +/- 3 (median 6). The corresponding values for the duodenal bulb 2 +/- 4
      (median 0) and 4 +/- 5 (median 0), respectively. Both drugs averaged were
      generally well tolerated. In summary, piroxicam-beta-cyclodextrin given as a 20
      mg single oral morning-dose over a 14-day period was significantly better
      tolerated than piroxicam 20 mg with regard to gastroduodenal damage.

PMID- 9235812
TI  - [Helicobacter pylori associated gastrointestinal mucosal lesions: is there an
      increased risk during therapy with nonsteroidal antirheumatic agents?].
AB  - ENDPOINTS: Are there connections between Helicobacter pylori-induced and NSAID
      induced gastrointestinal mucosal lesions leading to an increased risk? Are there
      any diagnostic or therapeutic consequences? METHODS: Evaluation of H.P.
      infection, NSAID medication and mucosal lesions in 303 patients with rheumatic
      diseases. RESULTS: The prevalence of H.P. infection was 67.7%. Positive H.P.
      antibodies were found in 96.2% of patients with mucosal lesions, confirmed by
      endoscopy. There was no statistically significant increase of mucosal lesions in
      patients with both H.P.-infection and NSAID therapy. CONCLUSIONS: The main cause
      for gastrointestinal mucosal lesions is H.P. infection (> 90%). A general
      mucoprotective therapy in patients with H.P. infection and NSAID therapy cannot
      be supported. It may be supposed that a part of mucosal lesions connected to
      NSAID-therapy in recent decades probably was the consequence of H.P. infections.
      Eradication of H.P. might be of higher importance in the future.

PMID- 9235814
TI  - [Therapeutic approaches of general practitioners and rheumatologists in South
      Germany in rheumatoid arthritis and gonarthrosis].
AB  - Using "paper patients" we compared the therapeutic approaches of general
      practitioners and rheumatologists to rheumatoid arthritis and to osteoarthritis
      of the knee. The mailed survey contained a mild, a moderate and a severe case of
      rheumatoid arthritis (RA) and a case of osteoarthritis (OA) of the knee. 111 out
      of 252 general practitioners and 78 out of 132 rheumatologists selected at random
      participated in the study. We found that rheumatologists would choose more non
      steroidal anti-inflammatory drugs (NSAID), disease modifying antirheumatic drugs
      (DMARD), steroids and physical therapy. In case 4 (OA of the knee)
      rheumatologists would more frequently recommend analgesics, local steroids,
      occupational therapy, surgery and ortheses. Primary care physicians on the other
      hand prescribed more chondroprotective agents. Patients with RA and OA of the
      knee would be treated differently by primary care physicians and rheumatologists.
      In order to develop a more uniform therapeutical concept and therefore to reach a
      better management of the rheumatic patient, a close co-operation of the two
      physician groups is needed.

PMID- 9235815
TI  - [Alprostadil (PGE 1) and cyclosporin A in treatment of vasculitis in rheumatoid
      arthritis].
AB  - A 56-year old female patient with rheumatoid arthritis and histologically
      verifiable vasculitis with necrosis around the nail bed and distal phalanx
      gangrene on both hands as well as skin ulcers on both thighs was treated over 16
      weeks with Cyclosporin A, glucocorticoids and Alprostadil. This immunosuppressive
      therapy resulted in a clinically relevant improvement of acral microperfusion
      with complete remission of nail bed necrosis and of gangrenous distal phalanxes.
      Due to improved tissue perfusion the deep ulcers on both thighs could granulate
      and were closed by proliferative connective tissue, and the high-positive
      immunological parameters CIC, CRP and the number of activated T-cells normalized.

PMID- 9235817
TI  - [Guidelines for primary management of patients with craniocerebral trauma.
      Intensive Care Medicine and Neurotraumatology Working Group of the German Society
      of Neurosurgery. Scientific Neuroanesthesia Circle of the German Society of
      Anesthesiology and Intensive Care Medicine].

PMID- 9235816
TI  - [Hemangioblastoma: description of a disease picture and report of 41 cases].
AB  - Hemangioblastomas are benign tumors of the central nervous system (CNS) with a
      predominance of the cerebellar hemispheres. They are one of the most frequent
      tumors of the posterior fossa in adults. In this retrospective study the data of
      41 operated patients (23 men and 18 women) with a hemangioblastoma of the CNS are
      demonstrated. The mean age of the patients was 42.2 years (Range 4-70 years). 76%
      of the hemangioblastomas were located in the cerebellum, 9% in the cerebral
      hemispheres, 7% in the spinal canal and 5% in the brain stem. Signs of increased
      intracranial pressure and cerebellar dysfunction were the most frequent symptoms.
      Complete tumor removal was achieved in 90% of all operated cases. 82% of the
      hemangioblastomas were cystic and 18% solid. The mean diameter of the tumor cysts
      was 36 mm (Range 20-60 mm) and 18 mm (Range 2-40 mm) of the solid tumors. In 7%
      of the cases tumor recurrence was seen with a mean time interval of 5.7 years.

PMID- 9235818
TI  - [Monitoring and therapy concepts in increased intracranial pressure. Intensive
      care medicine in increased intracranial pressure. "Intensive Care Medicine"
      Expert Forum of the German Society of Anesthesiology and Intensive Care
      Medicine].

PMID- 9235819
TI  - [Pathophysiology of brain edema].

PMID- 9235820
TI  - [Physiology and pathophysiology of intracranial pressure].

PMID- 9235821
TI  - [Monitoring cerebral perfusion pressure].

PMID- 9235822
TI  - [Value of electroneurophysiological monitoring on the intensive care unit].

PMID- 9235823
TI  - [Value of transcranial Doppler ultrasound in increased intracranial pressure].

PMID- 9235824
TI  - [Monitoring cerebral oxygenation in increased intracranial pressure].

PMID- 9235825
TI  - [Intra-clinic transport of patients with increased intracranial pressure].

PMID- 9235826
TI  - [The comparative characteristics of the otoneurological disorders and of the
      computed and magnetic resonance tomographic data in tumors of the pineal area].
AB  - A hundred and twenty patients with pineal tumors were examined and analyzed. All
      the patients underwent detailed otoneurological examination supplemented by vocal
      and tone audiometry, electronystagmography. Computerized tomography (CT) with
      contrast reinforcement was made in all the patients. Magnetic resonance imaging
      (MRI) was conducted in 43 patients. Based on the findings, otoneurological
      symptomatology and CT and MRI data were compared. All the patients were divided
      into 4 groups by the size of a tumor and by the magnitude of its impact, as
      evidenced by CT and MRI. Comparing the findings, it can be concluded that with
      larger pineal tumors and the increased decompensation of a process there is a
      steady rise in the incidence of some otoneurological symptoms. Nevertheless,
      there is a clear relationship of otoneurological manifestations to the
      predominant growth of pineal tumors into the diencephalic area or into the
      posterior cranial fossa, by affecting truncal cochleovestibular formations and
      tumor sizes.

PMID- 9235827
TI  - [The function of the superior sagittal sinus in parasagittal meningiomas based on
      data from angiography and intraoperative ultrasonic diagnosis].
AB  - The results of examining patients with parasagittal meningiomas were first
      compared by angiography and intraoperative ultrasound diagnosis. The significance
      of each method was defined. A correlation was found between the data obtained by
      the two techniques and the functional status of the upper sagittal sinus by
      taking into account each angiographic phase. It is concluded that intraoperative
      ultrasound diagnosis is of highly informative significance and it should be
      obligatorily used while removing parasagittal meningiomas in order to maintain
      the anatomic integrity of the upper sagittal sinus.

PMID- 9235828
TI  - [Transcutaneous radiofrequency destruction of the articular nerves in treating
      low back pains].
AB  - Lumbar pain is a most common suffering which frequently becomes chronic. In the
      mechanical low back syndrome caused by an abnormality in the intervertebral
      joints, lumbar pain may be rather easily differentiated from pain induced by to
      spinal root compression due to discal hernia or intervertebral foramen stenosis.
      The absence of benefits from conservative treatment of lumbar pain caused by
      intervertebral joint abnormalities is an indication for the highly effective and
      low-traumatic surgical technique transcutaneous radiofrequency destruction of
      intervertebral facette nerves. The technique yields good results in small
      displacements of the lumbar vertebra which cannot undergo orthopedic
      interventions, as well as in severe vertebral deformities which cause a higher
      load on the intervertebral joints.

PMID- 9235829
TI  - [The orthostatic resistance of the cerebral and peripheral circulations in
      patients with contusive brain lesions].
AB  - Orthostatic tests with printing recording of EEG, REG, RVG were used to examine
      the functional status of the truncal level of circulatory regulation in patients
      with brain confusions. Within the first 24 hours after brain injury there was a
      significant reduction in the pulse blood filling of cerebral vessels in the
      vascularization areas of carotid and vertebral arteries along with higher
      vascular tone; pulse blood filling of peripheral vessels in the lower extremities
      remained normal with a marked decrease in their vascular tone. Orthostatic tests
      showed the asymmetric enhancement of a dilating arterial response in the virtual
      absence of a constrictive response of lower extremity vessels. Following 2-3
      weeks of brain injury, cerebral and peripheral hemodynamics tends to normalize:
      in orthostasis, the responsive dilatation of cerebral vessels diminished, inter
      hemispheric asymmetry levelled; as compared to the normal values, cerebral
      vasodilation, however, remained enhanced with drastically suppressed peripheral
      vascular responsiveness. The described impaired vascular responsiveness were more
      evident in the presence of EEG truncal dysfunction syndromes. The findings
      suggest that central regulatory disorders of vascular tone play an important role
      in the pathogenesis of traumatic brain disease. A particular phasic periodicity
      of vascular responses to orthostatic exposure, which are characteristic of the
      acute and early rehabilitative periods of moderate brain injury.

PMID- 9235830
TI  - [Immunopathology in craniocerebral trauma].
AB  - Changes in anticerebral autoantibody titers were examined in the serum and spinal
      fluid of 118 patients in acute and residual brain injury. The mechanisms of
      immune processes were studied in relation to the severity of injury and the
      clinical manifestations of the disease. The examination of anticerebral
      autoantibody titers was found to be of high informative value.

PMID- 9235831
TI  - [A macro- and microscopic study of the status of the deep and median structures
      of the lymph circulatory system in craniocerebral trauma].
AB  - Craniocerebral injuries involve changes in the vascular plexuses and ependyma of
      the ventricles, and the severity of these changes varies, depending on the
      duration of the posttraumatic period and severity of the injury. Analysis of the
      time course of pathomorphological changes in the cerebral ventricular structures
      extend our notions on the role and impact of liquor circulation in the
      pathogenesis of craniocerebral injury. Structural changes in the vascular
      plexuses may disorder the function of the blood-liquor barrier and promote the
      development of hydrocephalus. Changes in the structure of the ependymal membrane
      may involve dysfunction of the liquor-encephalic barrier of the inner surface of
      the brain and promote the development of brain edema.

PMID- 9235832
TI  - [A giant histiocytoma of the occipital area].

PMID- 9235833
TI  - [The structure and hemodynamics of arteriovenous malformations of the spinal
      cord].
AB  - The structure and hemodynamics of arteriovenous malformations of the spinal
      marrow are first described in the Russian literature on the basis of 93 cases
      with spinal marrow arteriovenous aneurysms (SMAA) verified by selective spinal
      angiography. The angiographic pattern of SMAA (their site, blood supply, and ways
      of outflow) is given in detail. Analysis and clinical tests made it clear that
      80% of the patients had subarachnoidal hemorrhage and 60% had recurrent and
      multiple hemorrhage. Prior to angiography 35 patients had undergone myelography
      with water soluble contrast agents and 42 had magnetic resonance imaging.
      Combined vascular lesions in the spinal marrow and other organs were revealed in
      20% of the patients. The malformations were divided into 4 types by the
      angiographic findings of their structure and hemodynamic parameters.

PMID- 9235834
TI  - [An arteriosinusal anastomosis between the middle meningeal artery and the
      cavernous sinus. Its surgical treatment using the balloon catheter].

PMID- 9235835
TI  - [A puncture cannula-retractor for brain tissue].

PMID- 9235836
TI  - [The history of the development of neurosurgery in the Nizhegorod region].

PMID- 9235837
TI  - [The first department of neurosurgery in Russia].

PMID- 9235838
TI  - [Spinal cord trauma: the current concepts of the mechanisms of the damage,
      regeneration and means for its correction].

PMID- 9235839
TI  - [Combat injuries to the spine and spinal cord].

PMID- 9235840
TI  - [The morphology of the vascular spasm in cerebral aneurysm rupture].
AB  - The vessels of the basis cerebri were histologically examined in 45 patients who
      had died from arterial aneurysmal rupture. Angiography had made at the clinic
      detected cerebral vasospasm of varying severity and extent. All autopsies showed
      ischemic encephalomalacia in specimens. The findings indicated that
      arteriostenosis angiographically identified as vasospasm, by causing ischemic
      events was induced by morphological changes in the arterial wall. The arterial
      structural changes found were characterized by subsequent changes in the intima,
      elastic membrane, and medial layer.

PMID- 9235841
TI  - [Health care delivered to Portuguese children. The past, present and new
      challenges].
AB  - The socio-economic development of a country as well as the state of its health,
      its communications network, cultural level and health care organisation together
      affect what is known as the health indicators. Portugal belongs to the group of
      UNICEF countries with the best indicators in what concerns infant mortality and
      death below the age of five. It is still, however, 25th and 28th respectively at
      world level. The authors review some of the factors which have most contributed
      towards the progress of the indicators over the last twenty years, namely, the
      role played by general practitioners, the creation of health centers, the
      development of a maternal-infant assistance programme and the activity of Central
      and District Hospitals. They analyse the recent maternal-infant programme and
      discuss the main short and mid-term problems in the perinatal and paediatric age
      groups. The socio-economic changes seen in Portuguese society, together with
      sociological changes and those observed in the field of pathology, call for a new
      approach in the organisation of care which includes the need for a new dialogue
      between the different health structures of a society, namely, through maintaining
      the functional coordinating maternal-infant units, the creation of the same units
      for paediatrics, new efforts by the general paediatrician, the community
      paediatrician and the sub-specialised paediatrician together with the general
      practitioners within a specific action programme of a Health Unit.

PMID- 9235842
TI  - [A different college of pediatrics].

PMID- 9235843
TI  - [Anti-hepatitis B and anti-Haemophilus influenzae type b vaccines].
AB  - The epidemiologic aspects of hepatitis B are analysed. The author proposes the
      vaccination of all children, risk groups and teenagers. Also the high incidence
      of Haemophilus influenzae infections in Portugal justifies the use of an anti-Hib
      vaccine administered to all children under 5 years, preferentially in the first
      year of life.

PMID- 9235844
TI  - [The use and interpretation of tuberculin tests].
AB  - The author reviews the difficulties in diagnosing tuberculosis infection with the
      current BCG National Vaccination Plan. The author points out some directions
      that, in her point of view, may provide a clearer interpretation of the
      tuberculin skin test, bearing in mind the child's clinical, epidemiologic and
      social background.

PMID- 9235845
TI  - [How our pediatric services work].
AB  - The results of a questionnaire sent by the College of Pediatrics of the
      Portuguese Doctors Association (Ordem dos Medicos) to the pediatric departments
      all over the country are presented. From the answers of fifty-one services,
      physical conditions, equipment, human resources, assistancial and scientific
      activities developed are characterized.

PMID- 9235846
TI  - [Foreign bodies in the tracheobronchial tree. 12 years' experience].
AB  - During a period of twelve years--January 1983 to December 1994, 371 children
      suspected of foreign body inhalation were admitted in Hospital Pediatric of
      Coimbra. The diagnosis was confirmed in 200 of them (54%), and this group was
      analysed. The incidence has increased until 1989 and stabilized in the last 5
      years with a median of 18 cases/year. Two third of the children were boys and 84%
      were under three years old. A history of choking was obtained in 87% of the
      patients but only 39% of the cases had an early diagnosis (within 24 hours). The
      most frequent clinical findings were abnormal auscultation, sternal retraction,
      cough, wheezing and fever. Sixty percent of them were asymptomatic. The chest
      radiology findings were air trapping in 45%, consolidation in 21% and in 17%
      there were no abnormalities. Radiopaque foreign bodies were found in 9%. Organic
      bodies were the most frequent (74%) and among these, peanuts, lupines and beans.
      Food aspiration in one case took to cardiorespiratory arrest and in another with
      a late diagnosis bronchial stenosis needed a surgical treatment. Complications of
      foreign bodies extraction had no consequences.

PMID- 9235847
TI  - [Acute pericarditis in childhood. The 9-year experience of a tertiary referral
      center].
AB  - Sixteen children, aged 7 months to 12 years, with acute pericarditis, admitted
      between 1985 and 1993 to a tertiary referral centre were analyzed retrospectively
      for their presentation, etiology, work-up, management and prognosis. It was found
      that most of the presenting signs were not specific and were often related to
      associated diseases such as respiratory tract infections. In 50% of the cases a
      cause was not found, the others had viral infections (12.5%), tuberculosis
      (12.5%), Haemophilus influenzae infection (6.25%), Toxocara canis infection
      (6.25%) and collagen diseases (12.5%). In eight cases non-steroidal anti
      inflammatory drugs associated with steroids were given, 7 patients received non
      steroidal anti-inflammatory drugs and 1 steroids. The mean follow-up time was 3
      years (1 to 5). Six patients had one or more relapses. Five of the 6 patients
      with relapses were in the group which received steroids. The two patients with
      tuberculosis underwent pericardiectomy. One child died due to complex heart
      disease and the remaining 15 were cured. It was concluded that in pericarditis an
      extensive work-up may not reveal the major etiologies and that long term
      prognosis is good.

PMID- 9235848
TI  - [A comparison of 4 pregnancy assessment scales (CRIB, SNAP, SNAP-PE, NTISS) in
      premature newborns. Clinical Risk Index for Babies. Score for Neonatal Acute
      Physiology. Score for Neonatal Acute Physiology-Perinatal Extension. Neonatal
      Therapeutic Intervention Scoring System].
AB  - In recent years a number of neonatal risk scores have been developed in order to
      assure a more accurate evaluation of results obtained by different NICU's. It is
      noteworthy that throughout the years an effort has been made to adapt the scores
      to the specific neonatal problems and to make them easier to use. We felt that it
      would be important to compare various scores (CRIB, SNAP, SNAP-PE, NTISS) in a
      population of premature infants. This was the main objective in this study.
      Between January 1992 and February 1995 a total of 186 infants with birthweight
      under 1500 grams and/or gestational age under 32 weeks were admitted to our Unit.
      There were 40 deaths (21.5%). It was possible to use the four above mentioned
      scores retrospectively. The area under the ROC curve (for predicting in-hospital
      mortality) in each score was: CRIB 0.90; SNAP 0.88; SNAP-PE 0.88; NTISS 0.85. The
      CRIB score was easier to perform (only 5 minutes, in contrast to 20-30 minutes
      for the other scores). From this study CRIB score is apparently a suitable and
      accurate method easily performed in clinical practice.

PMID- 9235849
TI  - [A cost-benefit evaluation of prenatal diagnosis performed at a referral center
      with a population with a genetic or abnormality risk].
AB  - Prenatal diagnosis (PND) has assistencial, psychological and economical
      consequences; it is very important to evaluate cost effectiveness for the
      population. A prospective study was done (longitudinal and descriptive) on a
      population referred to Maternidade Dr. Alfredo da Costa, divided into two groups.
      Group one with PND performed on proper time and second group a PND procedure
      performed on a adequate time. The general characterization, indications for
      reference and consequences were evaluated. The conclusions are that the
      indications for reference were correct and the diagnosis was effective in 17% of
      patients. Social, economical levels and multiparity were the most important
      factors affecting adequate PND. However concerning the results, the termination
      of pregnancy was more performed on the group 1 and more abnormalities were seen
      on the newborns of group 2.

PMID- 9235850
TI  - [Delayed primary anastomosis in esophageal atresia without fistula. 10 years'
      experience].
AB  - From 1984 until 1994 there were 7 cases of newborn with esophageal atresia
      without fistulae, five of which were treated through primary anastomosis and two
      of these presented exceptional long gaps. This article is an analysis of these 7
      newborns, their post-operative complications and the therapeutics used. Two
      deaths occurred due to associated serious cardiac pathologies, which made delayed
      primary anastomosis impossible, and one sudden death four months after the
      esophageal anastomosis. Three of these cases present a good stature-weight
      progression and one remains slightly under the 5 percentile. Considering our
      results, the delayed primary anastomosis in the esophageal atresias with long
      gap, in spite of the post-operative complications, shall continue to be the
      author's choice.

PMID- 9235851
TI  - [Mechanical ventilation near large centers. The experience of a perinatal care
      unit].
AB  - A retrospective study of the newborns who were submitted to mechanical
      ventilation at the Neonatal Intermediate Care Unit was made between July 1991 and
      June 1994. Mechanical ventilation in such a unit should be transitory and not
      exceed 24 hours. Information concerning pregnancy, labour, neonates, type of
      ventilation and its problems was gathered. Forty seven neonates were ventilated.
      The average ventilation time was six hours (1-20 hours). The main cause of
      ventilation was hyaline membrane disease which occurred in 24% of all cases.
      Mortality observed was 16.6% and some sequellae were registered which were
      related not only to ventilation but also to the basic pathology in 26% of cases.

PMID- 9235852
TI  - [Acute infantile bilateral striatal necrosis].
AB  - This paper describes the clinical case of a nine year old child clinical features
      of tetraparesis and acute encephalopathy after an infectious disease. The brain
      magnetic resonance imaging was compatible with a symmetrical bilateral necrosis
      of the brain nucleus which, associated with the clinical evolution, led to the
      diagnosis of acute bilateral infant striatal necrosis.

PMID- 9235854
TI  - [Hepatic fascioliasis].
AB  - Hepatic fascioliasis is a pathology with an increasing incidence, morbidity and
      mortality all over the world and most particularly in our country, where endemic
      spots have been found, particularly in rural areas. Based on a clinical case
      which is supported by a revision of appropriate literature, the authors have made
      relevant considerations on bio-ecology, diagnosis, prognostic and treatment of
      this disease.

PMID- 9235853
TI  - [Mucoviscidosis with respiratory symptomatology in the neonatal period].
AB  - A case of cystic fibrosis presented in the neonatal period with respiratory
      symptomatology associated with early pancreatic insufficiency is reported. The
      CFTR gene molecular analysis was found to be a compound heterozygotes for delta
      F508 and G542X. The rarity of this mode of presentation and the inclusion of this
      entity in the differential diagnosis for neonatal respiratory distress syndrome
      is emphasised. The pathogenesis and some therapeutic aspects carried out in our
      patient, which might have improved the life expectancy of patients with this
      disease, are discussed.

PMID- 9235855
TI  - [Pneumoperitoneum in bladder rupture].
AB  - Pneumoperitoneum is rarely seen with bladder rupture. In blunt abdominal trauma
      this sign is strongly suggestive of gastric or bowel perforation. In our child,
      suspicion of bladder trauma was evoked by car belt marks in the hypogastrium and
      by gross hematuria. Preoperative diagnosis was not confirmed because immediate
      surgical exploration was required based on the presence of free air in the
      abdominal roentgenograph.

PMID- 9235857
TI  - 12th Annual International Symposium on Acupuncture and Electro-Therapeutics. New
      York City, New York, October 17-20, 1996. Abstracts.

PMID- 9235856
TI  - [The death of Fernando Pessoa. The differential diagnosis of liver colic].
AB  - A clinical review of the most probable cause of death of the poet Fernando Pessoa
      is made. The many times cited final diagnosis of "hepatic colic" and the limited
      clinical information available are considered. The spectrum of chronic alcoholism
      and its risks are questioned by recent advances on pathology knowledge.

PMID- 9235858
TI  - [Unusual clinical presentation of Meckel's diverticulum. A case report].
AB  - Meckel's diverticulum (Md) is the most common congenital anomaly of the
      gastrointestinal tract. It results from an incomplete obliteration of the
      omphalomesenteric duct during fetal life. It is frequently located on the
      antimesenteric border of the ileum at 80 cm from the ileum-cecal valve. It
      contains heterotopic mucosa in 30% of the cases and in 70% of these the mucosa is
      of the gastric type. The most common complication in childhood is represented by
      hemorrhage. Preoperative diagnosis is often difficult. Barium enema, Tc-99
      scintigraphy and selective mesenteric angiography usually can permit diagnosis.
      In adults occlusion, perforation, diverticulum infection, Littre's hernia and
      tumors represent the complications of Meckel's diverticulum. A case of Md is
      reported because of the unusual clinical presentation.

PMID- 9235859
TI  - [Hyperthyroidism and carcinoma of the thyroid gland].
AB  - The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as
      low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters.
      Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a
      few tumors are suspected preoperatively with ultrasonography or fine needle
      aspiration or 131 I scan. In 408 patients who underwent surgery for
      hyperthyroidism in our Surgery Department from January 1967 through December 1994
      the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm
      occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of
      toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%).
      19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in
      hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in
      toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves'
      disease. A papillary carcinoma was diagnosed preoperatively on fine needle
      aspiration with ultrasonography in only two patients with Graves' disease and
      confirmed by postoperative histological examination on permanent section. We do
      not believe in the frozen-section examination intraoperatively because it's not
      diagnostical for follicular lesions and evaluates rarely capsular invasion.
      Twenty patients received total thyroidectomy and four of them also
      lymphoadenectomy. Three patients received emithyroidectomy: in two cases for
      occult papillary carcinoma and in the last case for local cancer invasion
      (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence.
      Mean follow-up is 59.6 months. Our retrospective study shows a progressive
      increase of the incidence of coexisting thyroid malignancy and hyperthyroidism
      especially in toxic nodular goiter, probably related to extended surgical
      indications. Our findings do confirm that, even in the presence of
      hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of
      malignancy.

PMID- 9235860
TI  - [Results of a cytological study of needle aspiration in 85 cases of nodular
      pathology of the thyroid gland, surgically controlled].
AB  - The present retrospective study is related to 85 patients with nodular thyroid
      pathology submitted to surgical therapy. In these patients preoperative cytology,
      through fine needle biopsy aspiration (FNBA), has been compared with histological
      examination performed on the surgical specimen. Malignant lesions were detected
      in 30 cases (35.3%). True positives cases were 14, true negative 48, false
      positive and false negative (FN) were 2 and 3 respectively. Due to the high
      number of FN, sensibility of FNBA was only 51.8%, specificity was 96% and
      accuracy 80.5%. Positive and negative predictive value were 87.5% and 78.6%
      respectively. CONCLUSIONS: Evaluation of the several sources of error comes to a
      conclusion that FNBA is certainly the main diagnostic tool in nodular thyroid
      pathology. Its employment should undergo to a centralized diagnostic evaluation
      in such a way that cytology is analysed together with clinical and other
      instrumental data.

PMID- 9235861
TI  - [DRG classification system and administrative innovations in Servizio Sanitario
      Nazionale: future implications for professionals, managers and patients].

PMID- 9235862
TI  - [Validity, limitations and indications of intraoperative dosage of parathyroid
      hormone (I-PTH) in the surgical treatment of primary hyperparathyroidism].
AB  - INTRODUCTION: Recently new methods have been experienced to achieve the best
      surgical results in complete removal of pathological parathyroid tissue; serum I
      PTH (1-84) rapid dosage is the most interesting and reliable method. MATERIAL AND
      METHODS: In a group of 11 patients with IPP, diagnosed by high levels of I-PTH,
      total and ionized serum calcium, 7 were paucisymptomatic, 3 presented
      nephrolityasis, 1 acute pancreatitis and severe hypercalcemic crisis. No MEN were
      found. A systemic research of all parathyroid glands was always performed, then
      10, 20, 30 and any 30 minutes after each parathyroidectomy serum I-PTH rapid
      dosage was made (rapid IRMA method) until the end of surgical treatment. RESULTS:
      Eight single adenomas parathyroid were diagnosed, 1 double adenoma and 2
      hyperplasia. All patients had high levels of serum I-PTH during pathologic
      parathyroid removal. The decrement of I-PTH level to 40% 10 min after
      parathyroidectomy, and 50% after 20 minutes confirmed the efficacy of surgery.
      DISCUSSION: Intraoperative rapid dosage of I-PTH associated with
      anatomopathologic results leads to a successful diagnosis and therapy. Sometimes
      in multiglandular disease serum level of PTH decreases after first
      parathyroidectomy as in a single adenoma: this underlines the importance of
      systematic surgical research of all glands in any case. CONCLUSION: In our
      experience serum I-PTH rapid dosage in IPP would be applied by specialized
      surgical equipments only in selected patients, such as reoperation or those few
      cases of first surgical treatment when ectopy is suspected.

PMID- 9235863
TI  - [Natural history of breast cancer: lobular carcinoma versus ductal carcinoma in
      our experience].
AB  - Aim of the study is to evaluate the biology, the clinical evolution and the
      prognosis of lobular carcinoma of the breast. We retrospectively evaluated the
      patients treated in our institution during the last 13 years. 117 patients with
      lobular carcinoma of the breast and 117 patients, randomized out of 397 patients
      with 'classical' pattern of ductal carcinoma were compared. Age distribution,
      type of surgery, tumor size, TNM stage, axillary lymph node involvement,
      multifocality, multiple breast cancers, local and distant recurrences, overall
      survival and disease-free survival have been evaluated. There was not a
      significant difference in tumor size, lymph node involvement, stage distribution,
      estrogens and progesterone receptors status, local and distant recurrences. The
      only significant differences were found in multifocality and multiple breast
      cancers. The said difference does not seem to modify the overall survival and the
      disease-free survival that are the same in the two groups. Our research shows
      that tumor size and axillary lymph node status are the only elements that have to
      be considered in the choice of the surgical treatment and prognosis. It seems
      that the difference in distant metastatic pattern between lobular and ductal
      carcinoma is the distinctive feature in the follow-up of these patients.

PMID- 9235864
TI  - [Immediate reconstruction after radical mastectomy using Becker's prosthesis:
      long-term results].
AB  - The authors present their experience about 36 immediate breast reconstruction
      after radical mastectomy by Becker's prostheses, concerning early and delayed
      postoperative complications, cosmetic results and patients satisfaction. The
      indication to reconstruction has been proposed considering stage disease, breast
      features (volume, skin flaps, symmetry with the other breast). The postoperative
      mortality was none; overall incidence of early complications was 11% and in two
      cases has obliged to implant removal. Mean follow-up has been 31 months: a severe
      contracture (Baker IV) has been observed in 2 patients which obliged to implants
      removal 90% of the patients (20 cases) had no contracture (Baker I) whereas 2
      patients presented a Baker II contracture. The majority of the patients declared
      their complete satisfaction. Finally the authors suggest an immediate breast
      reconstruction after radical mastectomy because this procedure has a low
      incidence of complications and contracture and it can be surely done by a general
      surgeon.

PMID- 9235865
TI  - [Incidentalomas of the adrenal gland].
AB  - The wider application of radiological examinations (ultrasound, computed
      tomography) has led to the pre-clinical discovery of "masses" in some organs,
      especially in adrenal gland. As these tumors are incidentally discovered, they
      are called "incidentalomas", and this term has been universally accepted. As soon
      as adrenal incidentaloma has been diagnosed it is important to establish if the
      patient has to undergo immediate surgical exploration or it is possible to follow
      the patient radiologically. Hormonally active adrenal metastatic tumors and
      adrenal incidentalomas greater than cm 5 should be surgically treated, while
      other adrenal tumors can be followed radiologically. Median anterior laparotomy
      or bilateral subcostal incision give a good surgical view. It is important the
      cooperation with endocrinologist, cardiologist and anaesthetist in order to
      control possible hypertensive rises during surgical operation.

PMID- 9235866
TI  - Radionuclide venography and the surgical treatment of chronic venous disease of
      the lower extremity.
AB  - PURPOSE: The purpose of this study was to describe the use of radionuclide
      venography in detecting the site and the functional value of blood reflux through
      incompetent perforating veins of the leg of patients with chronic venous disease.
      METHODS: In this study we evaluated the management of 29 patients (34 lower
      limbs) who were admitted with chronic venous disease of the lower limbs (in 7
      with ulcers refractory to conservative management), surgically treated between
      1991 and 1994 on the basis of physical examination and scintigraphic detection of
      pathological venous refluxes. RESULTS: In 26/29 patients (31/34 legs = 91%) there
      was a good result with no recurrence and complete alleviation of symptoms. All
      the ulcers healed but in two cases recurred after 2 and 6 months respectively.
      Amelioration of leg tropism was achieved in all patients with a good "cosmetic"
      result in 27/34 legs (79%). A complete deconnection of the incompetent
      perforating veins was confirmed with radionuclide venography in 31/34 legs (91%).
      CONCLUSIONS: The authors conclude that radionuclide venography is useful in the
      pre-operative evaluation of patients with chronic venous disease of lower
      extremity.

PMID- 9235867
TI  - [Evaluation of the surgical risk and preparation to major surgical intervention
      in geriatric surgery].
AB  - BACKGROUND: The progress in surgery, anaesthesia, pre and postoperative care
      improves the number of old patients undergoing major surgery. The preoperative
      physiologic assessment is very important to identify patients who are at higher
      risk group and to plan the therapeutical strategics. METHODS: This study has been
      carried out on 849 patients aged 70 years and over who underwent major surgery;
      biliary tract surgery in 314 cases, colorectal in 279, gastroesophageal in 144,
      vascular in 48, jejunal in 32, pulmonary in 13, pancreatic in 11, hepatic in 8.
      158 patients underwent urgency surgery. Mortality and morbidity index are related
      to the age of the patients, the urgency of the treatment, the time required for
      the operation, the preoperative physiologic assessment. RESULTS: The overall
      mortality rate was 13.7%: 84 patients died for cardiovascular complications and
      32 for pulmonary complications. Mortality rate was 6% after elective surgical
      treatment and 48% in urgency. The urgency influences considerably the mortality
      in the group over 80 years than in younger (p < 0.01). The difference in
      mortality after elective surgery was less significative (p < 0.06). The time
      required for the operation doesn't influence the mortality rate. CONCLUSION: The
      authors emphasize that the preoperative physiologic assessment to identify
      patients at higher risk and an accurate preoperative care may reduce the
      mortality rate also in patients over 80 years undergoing major surgery. In
      urgency, when the patients cannot undergo a preoperative assessment and care, the
      postoperative mortality is higher in the group over 80 years than in younger.

PMID- 9235868
TI  - [Biliary surgery in the aged].
AB  - Between 1980 and 1995 in the Section of General and Oncological Surgery of the
      Department of Surgery of the University of Catania, on a total of 1715 biliary
      surgical procedures, 926 were performed on the elderly patients, 287 of which in
      emergency. Cholelithiasis (469 cases) morbidity 4.5%, mortality 0.4%; acute
      colecystitis, (247 cases) morbidity 21%, mortality 12%. Choledocholithiasis (122
      cases) surgical treatment (51 cases) morbidity 21.6%, mortality 3.9%; endoscopic
      treatment (71 cases) morbidity 9.4%, mortality 0%. Neoplasms of the biliary tract
      (48 cases) diagnostic laparotomises 9, surgery (27 cases) morbidity 37%,
      mortality 11%; endoscopy (12 cases) morbidity 33%, mortality 0%. Acute
      obstructive cholangitis (34 cases), surgical drainage (9 cases) morbidity 55%,
      mortality 33%; endoscopic drainage (22 cases) morbidity 14%, mortality 4.8%;
      transhepatic drainage (3 cases) morbidity 66%, mortality 33%. Acute biliary
      pancreatitis (6 cases) surgery (2 cases) morbidity 100%, mortality 50%; endoscopy
      (4 cases) morbidity 25%, mortality 0%. This experience confirms that in elderly
      patients the treatment of choice for cholelithiasis is cholecystectomy and for
      acute colecystitis is early cholecistectomy. The preferred treatment of
      choledocholithiasis and severe acute biliary pancreatitis is endoscopic
      sphincterectomy. Endoscopic or radiologic drainages are the choice for acute
      biliary pancreatitis. In conclusion elderly patients with surgical biliary
      problems should be treated by a surgical, endoscopic and radiological team,
      taking in account all the available procedures.

PMID- 9235870
TI  - [Small cell carcinoma of the esophagus: a case report].
AB  - The authors present the case of a primitive small cell esophageal carcinoma. It
      is a rare and biologically aggressive neoplasm which occurs mainly in the elder
      male. The case observed concerns a 69 year old female treated with surgical
      therapy consisting in esophagectomy and intrathoracic esophagealgastrictype
      plasty. Diagnostic problems either histological or immunohistochemical and the
      choice of the following treatment are discussed. The cases of patients treated in
      other Surgical or Oncological centers are reported. Therapeutic orientation
      adopted by our group is stressed. In this case we have chosen surgical therapy
      because a sure diagnosis come be given only on the base of the attent
      histological examination of the entire specimen (endoscopic biopsies are not
      sufficient); survival data reported are in favour of surgical treatment where
      secondary metastases are not evident in the respect of antiblastic therapy and/or
      radiotherapy. Neoplastic recurrence occurred ten months after and a metallic
      endoscopic esophageal prothesis was positioned. The patient died 1 year after
      surgery by mediastinal syndrome.

PMID- 9235869
TI  - [Effects on ventilation secondary to laparoscopic and laparotomic
      cholecystectomy].
AB  - OBJECTIVE: Evaluation of respiratory function after 24 hours from intervention
      related to two different surgical techniques of cholecistectomy. PATIENTS AND
      METHODS: Thirty patients submitted to cholecystectomy, nine by laparotomy and
      twenty-one by video-laparoscopy. The ventilatory parameters considered are as
      follows: CV, FCV, VEF1, FEF25-75%; and moreover also some variables of acid-base
      balance: pH, paCO2 e paO. RESULTS: In all cases was evidenced a decrease of
      respiratory activity. This phenomenon was more evident in the laparotomy group
      (CV = 37, 35, FCV = 41, 47, VEF1 = 40, FEF25-75% = 36.62% related to preoperative
      values versus 71.20, 80.88, 79.29, 77.91% in the videolaparoscopic group. No
      significative differences were registered between the two groups as to
      postoperative paO2, which was moderately lower in all patients, while no
      variation was observed for pH and paCO2. CONCLUSIONS: Data collected confirm that
      after laparoscopic cholecystectomy the ventilatory respiratory capacity is better
      conserved, that clinically means lower incidence of postoperatory pulmonary
      complications.

PMID- 9235871
TI  - [Cystic lymphangioma of the transverse mesocolon simulating neoplasm of the
      pancreatic tail].
AB  - Mesenteric cysts are uncommon lesions interesting surgeons above all for
      frequently difficulties in the preoperatory diagnosis. The role of radiology is
      to demonstrate the nature of these abdominal masses, but only with surgery we can
      establish a definitive histologic diagnosis. The authors report a case of a
      lynphangioma of the transverso mesocolon, miming a pancreatic neoplasm.

PMID- 9235872
TI  - [Acquisition of human bipedal gait from the viewpoint of the aquatic ape theory].
AB  - We are convinced that human bipedalism is better accounted for by the Aquatic Ape
      Theory than by the hypotheses, now commonly accepted, that the vertical gait is
      part of an adaptation for life in the savannahs. The advantages of the upright
      gait are easily understood by the versatility of this locomotion in a semi
      aquatic mode of life. Early hominid bipedalism cannot be described as an ideal
      adaptation for one isolated form of locomotion, since human bipedalism covers a
      wide range of locomoter behaviours such as diving, swimming, wading, climbing
      trees and rocks, and moving on land. This locomotor versatility, however, should
      not be confused with theories that consider humans and their ancestors as
      "primitive" or "unspecialized" creatures. The pronounced swimming and diving
      abilities of humans--and the features that make these abilities possible-
      represents the most striking element of our species locomotor spectrum in
      comparison with highly specialized "savannah primates". On the one hand baboons
      and geladas are clearly better-adapted to savannah conditions than humans are, if
      the acquisitions of modern technology are not taken into consideration. To these
      adaptations belongs quadrupedalism, which is the most common and successful form
      of locomotion among terrestrial tetrapods. On the other hand, humans are in most
      respects much better swimmers and divers than nonhuman primates even without
      technological help. The only satisfying explanation for these different
      adaptations of humans and nonhuman primates is provided by the Aquatic Ape
      Theory. It is the only model of humans evolution that accounts for the numerous
      examples of convergent features between people and other vertebrates and the only
      model that explains these convergences in connection with a well-defined
      ecological niche.

PMID- 9235873
TI  - [Discrepancies between police breath alcohol measurements in a field trial and
      blood alcohol concentration according to BGA guidelines and possible consequences
      for citizens].
AB  - Divergences between breath-alcohol values measured on the occasion of police
      field experiments and precise blood-alcohol determinations according to
      guidelines of the German National Institute of Health (BGA) are reported. In 169
      selected cases the difference of time between breath analysis and drawing the
      blood sample was less than 15 minutes. The consequences regarding forensic
      relevant cut-off values (0.8, 1.1, and 1.6/1000 resp.) are discussed.

PMID- 9235874
TI  - [Dual accidental carbon monoxide poisoning].
AB  - The bodies of 2 young men were discovered in the hut of a small garden plot. Due
      to the unclear circumstances of the deaths, a coroner's inquest was ordered. The
      cause of death was a carbon monoxide poisoning in both victims. At first the
      source of carbon monoxide was not detectable. According to the reconstruction of
      the fatal event, the only possible source of carbon monoxide was the charcoal
      grill found in the hut.

PMID- 9235875
TI  - [Errors in autopsy in Germany. Results of a multicenter study (II)].
AB  - In the result of a workshop held in Munster on 1st May 1993, 23 institutes of
      legal medicine in Germany reported death cases where the primary supposition was
      natural death or a death without legal relevance, but where the autopsies by
      chance revealed an unnatural death or a death with legal relevance. In the
      institutes participating in the study 13,000 autopsies were performed during the
      period of the reports, i.e. 75% of all legal autopsies performed in one year in
      Germany. A total of 92 "discoveries by chance" were reported where a natural
      death was given on the death certificate after the external examination of the
      corpse among them 49 accidents, 10 homicides, and 19 deaths by medical
      implications. In 717 deaths the manner of death was certified as "unclear" on the
      death certificate, but the autopsy revealed an unnatural manner of death. Some of
      these cases are also "discoveries by chance" after serious medical errors during
      the examination of corpses. Among these 717 cases were 35 homicides. It seems
      remarkable, that the prosecutors did not order a toxicological examination in
      several cases of fatal intoxications. Furthermore the results show that doctors
      often overlooked signs of carbon monoxide poisoning during the external
      examination of corpses. From errors made during the external examination another
      group of cases resulted which were initial classified as unnatural death without
      legal relevance, but the autopsy surprisingly revealed relevant facts. Finally in
      29 autopsies carried out after exhumation evidence of homicide was found in 3
      cases. On the basis of this multicentre study it can be estimated that there are
      at least 1200 homicide cases or 11,000 cases of unnatural death per year which do
      not appear in the official statistics and have been classified as natural death.
      The considerable grey area of fatal cases in connection with medical intervention
      resulting from the study (n > 2000) is also alarming. In addition at least 100
      undiscovered homicides are certainly included in the group of death cases
      certified as unclear during the external examination and where no autopsy was
      performed. Sources of the grey area are essentially errors made during the
      external examination of corpses and to a lesser degree incorrect decisions to
      release the corpse, mistakes were seldom made also by doctors performing the
      autopsy. The study shows a considerable grey area of unnatural death cases, which
      exists within the modern society of Germany. In face of this emphasis must placed
      on the historical demands of criminologists and forensic pathologists: reinforced
      education and further education of medical students and doctors in the field of
      the external examination of corpses. Introduction of a specialized medical
      external examination of corpses Adherence to the 3 classical classifications of
      the manner of death: natural, unnatural and unclear on the death certificate.
      Increased number of autopsies.

PMID- 9235876
TI  - [Legal and actual problems of autopsy and cadaver examination (section 87 StPO)
      (II)].

PMID- 9235877
TI  - [Analysis of cause of death in Central Rhine prisons and in police detention
      centers 1949 to 1990].
AB  - Using the documents from the Institute of Legal Medicine in Bonn, the deaths (86)
      in Middle Rhine detention centres and police custody since 1949 were
      investigated. All the deceased were male (average age 37, range: 18-67 years). As
      far as deaths from natural causes were concerned, death caused by myocardial
      infarction was the most frequent. The average age of myocardial infarction
      victims was 48. In two of these cases Koch's disease of the lung was diagnosed.
      Death of unnatural causes was the most frequently recorded, accounting for 63% of
      cases (suicide by hanging of incision injuries = 51%, and death by intoxication =
      12.5%). Hanging was the most common means of committing suicide usually being
      discovered in the morning. Items of clothing and cell windows were the most
      commonly used objects. Nearly all the suicides were under the influence of
      alcohol. In 6.8% of cases the drug tests were positive.

PMID- 9235878
TI  - [Suicide or fatal accident in fantasy play?].
AB  - The death by drowning of a 25-year-old man is reported, whose putrescent body was
      found drifting on the surface of an artificial lake. The deceased was dressed in
      a coat of chain-mail and trousers of the same material. The chain-mail clothing,
      which had a weight of 20 kg, reminded one of a knight's armour; it had been made
      by the wearer himself. Around the neck there were several turns of a chain
      running down to the legs and tying them together. According to the police
      investigations it is to be assumed that the man went out on the lake in a rubber
      boat and then pierced the air chambers of the boat with a knife. The possible
      background of the case in context with the special liking for fantasy games is
      discussed.

PMID- 9235880
TI  - A self-consistent mechanism for dealkylation in soman-inhibited
      acetylcholinesterase.

PMID- 9235879
TI  - Expression of human cholesterol 7alpha-hydroxylase in atherosclerosis-susceptible
      mice via adenovirus infection.
AB  - Adenovirus is a vector for the delivery of genes mainly to the liver. Short-term
      (approximately 3 days) studies using adenovirus transfection have provided
      valuable insights into how genes can complement normal and pathological
      phenotypes. When atherosclerosis-susceptible C57BL/6 mice were infected with an
      adenovirus vector containing the human 7alpha-hydroxylate cDNA (AV17h1) and fed
      on a chow diet, human 7alpha-hydroxylase mRNA and enzyme activity doubled
      compared with that in mice infected with an adenovirus vector (AV1Null) alone. In
      AV17h1-infected mice fed on a high fat cholic acid (HFCA) diet, mRNA expression
      and activity of both the endogenous and adenovirus (human) 7alpha-hydroxylase
      were repressed. AV17h1-infected mice fed on a HFCA diet and killed at mid-light
      had increased 7alpha-hydroxylase activity and mRNA compared with mice killed at
      mid-dark. Since expression of AV17h1 is driven by a constitutive Rous sarcoma
      virus promoter, the repression of human 7alpha-hydroxylase by the HFCA diet was
      unexpected. In spite of this post-transcriptional repression by the HFCA diet,
      AV17h1-infected mice expressed the human 7alpha-hydroxylase mRNA, causing its
      enzyme activity to be 3-fold greater than in AV1Null-infected mice. In AV17h1
      infected mice, the 7alpha-hydroxylase enzyme activity varied as a linear function
      of human mRNA abundance. In conclusion, the accumulation of apolipoprotein B
      containing lipoproteins in plasma of C57BL/6 mice fed on the HFCA diet was not
      reduced by longer-term (2 weeks) 7alpha-hydroxylase expression, probably because
      of its diminished expression caused by the diet and hepatic inflammation from the
      adenovirus infection. These results may suggest that adenovirus is effective in
      promoting longer-term (2 weeks) expression of 7alpha-hydroxylase.

PMID- 9235881
TI  - Aging of somanyl-acetylcholinesterase adducts: facts and models.

PMID- 9235882
TI  - Iron-sulfur clusters: nature's modular, multipurpose structures.
AB  - Iron-sulfur proteins are found in all life forms. Most frequently, they contain
      Fe2S2, Fe3S4, and Fe4S4 clusters. These modular clusters undergo oxidation
      reduction reactions, may be inserted or removed from proteins, can influence
      protein structure by preferential side chain ligation, and can be interconverted.
      In addition to their electron transfer function, iron-sulfur clusters act as
      catalytic centers and sensors of iron and oxygen. Their most common oxidation
      states are paramagnetic and present significant challenges for understanding the
      magnetic properties of mixed valence systems. Iron-sulfur clusters now rank with
      such biological prosthetic groups as hemes and flavins in pervasive occurrence
      and multiplicity of function.

PMID- 9235887
TI  - Distance-dependent electron transfer in DNA hairpins.
AB  - The distance dependence of photoinduced electron transfer in duplex DNA was
      determined for a family of synthetic DNA hairpins in which a stilbene
      dicarboxamide forms a bridge connecting two oligonucleotide arms. Investigation
      of the fluorescence and transient absorption spectra of these hairpins
      established that no photoinduced electron transfer occurs for a hairpin that has
      six deoxyadenosine-deoxythymidine base pairs. However, the introduction of a
      single deoxyguanosine-deoxycytidine base pair resulted in distance-dependent
      fluorescence quenching and the formation of the stilbene anion radical. Kinetic
      analysis suggests that duplex DNA is somewhat more effective than proteins as a
      medium for electron transfer but that it does not function as a molecular wire.

PMID- 9235888
TI  - Evidence for interacting gas flows and an extended volatile source distribution
      in the coma of comet C/1996 B2 (Hyakutake).
AB  - Images of comet C/1996 B2 (Hyakutake) taken during its close approach to Earth
      show differences in the distribution of gas and dust in the inner coma and reveal
      two arc-shaped molecular resonant emission features. The morphology of these
      features, as well as the apparent decoupling gas from dust in the inner coma,
      suggest that an extended region of icy grains surrounds the nucleus of Hyakutake
      and contributes substantially to the production of volatiles. Model simulations
      suggest the same conclusion and indicate that the brighter arc is explainable by
      the presence of a trailing condensation of ice-bearing granules with a rate of
      volatile production approximately 23 percent of that of the nucleus.

PMID- 9235889
TI  - Failure of parturition in mice lacking the prostaglandin F receptor.
AB  - Mice lacking the gene encoding the receptor for prostaglandin F2alpha (FP)
      developed normally but were unable to deliver normal fetuses at term. Although
      these FP-deficient mice showed no abnormality in the estrous cycle, ovulation,
      fertilization, or implantation, they did not respond to exogenous oxytocin
      because of the lack of induction of oxytocin receptor (a proposed triggering
      event in parturition), and they did not show the normal decline of serum
      progesterone concentrations that precedes parturition. Ovariectomy at day 19 of
      pregnancy restored induction of the oxytocin receptor and permitted successful
      delivery in the FP-deficient mice. These results indicate that parturition is
      initiated when prostaglandin F2alpha interacts with FP in ovarian luteal cells of
      the pregnant mice to induce luteolysis.

PMID- 9235890
TI  - Cross-language analysis of phonetic units in language addressed to infants.
AB  - In the early months of life, infants acquire information about the phonetic
      properties of their native language simply by listening to adults speak. The
      acoustic properties of phonetic units in language input to young infants in the
      United States, Russia, and Sweden were examined. In all three countries, mothers
      addressing their infants produced acoustically more extreme vowels than they did
      when addressing adults, resulting in a "stretching" of vowel space. The findings
      show that language input to infants provides exceptionally well-specified
      information about the linguistic units that form the building blocks for words.

PMID- 9235891
TI  - A G protein-coupled receptor phosphatase required for rhodopsin function.
AB  - Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors
      are phosphorylated by kinases that mediate agonist-dependent receptor
      deactivation. Although many receptor kinases have been isolated, the
      corresponding phosphatases, necessary for restoring the ground state of the
      receptor, have not been identified. Drosophila RDGC (retinal degeneration C) is a
      phosphatase required for rhodopsin dephosphorylation in vivo. Loss of RDGC caused
      severe defects in the termination of the light response as well as extensive
      light-dependent retinal degeneration. These phenotypes resulted from the
      hyperphosphorylation of rhodopsin because expression of a truncated rhodopsin
      lacking the phosphorylation sites restored normal photoreceptor function. These
      results suggest the existence of a family of receptor phosphatases involved in
      the regulation of G protein-coupled signaling cascades.

PMID- 9235892
TI  - Simplification of DNA topology below equilibrium values by type II
      topoisomerases.
AB  - Type II DNA topoisomerases catalyze the interconversion of DNA topoisomers by
      transporting one DNA segment through another. The steady-state fraction of
      knotted or catenated DNA molecules produced by prokaryotic and eukaryotic type II
      topoisomerases was found to be as much as 80 times lower than at thermodynamic
      equilibrium. These enzymes also yielded a tighter distribution of linking number
      topoisomers than at equilibrium. Thus, topoisomerases do not merely catalyze
      passage of randomly juxtaposed DNA segments but control a global property of DNA,
      its topology. The results imply that type II topoisomerases use the energy of
      adenosine triphosphate hydrolysis to preferentially remove the topological links
      that provide barriers to DNA segregation.

PMID- 9235893
TI  - A cytoplasmic inhibitor of the JNK signal transduction pathway.
AB  - The c-Jun amino-terminal kinase (JNK) is a member of the stress-activated group
      of mitogen-activated protein (MAP) kinases that are implicated in the control of
      cell growth. A murine cytoplasmic protein that binds specifically to JNK [the JNK
      interacting protein-1 (JIP-1)] was characterized and cloned. JIP-1 caused
      cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression. In
      addition, JIP-1 suppressed the effects of the JNK signaling pathway on cellular
      proliferation, including transformation by the Bcr-Abl oncogene. This analysis
      identifies JIP-1 as a specific inhibitor of the JNK signal transduction pathway
      and establishes protein targeting as a mechanism that regulates signaling by
      stress-activated MAP kinases.

PMID- 9235894
TI  - Analysis of a chemical plant defense mechanism in grasses.
AB  - In the Gramineae, the cyclic hydroxamic acids 2,4-dihydroxy-1, 4-benzoxazin-3-one
      (DIBOA) and 2,4-dihydroxy-7-methoxy-1, 4-benzoxazin-3-one (DIMBOA) form part of
      the defense against insects and microbial pathogens. Five genes, Bx1 through Bx5,
      are required for DIBOA biosynthesis in maize. The functions of these five genes,
      clustered on chromosome 4, were demonstrated in vitro. Bx1 encodes a tryptophan
      synthase alpha homolog that catalyzes the formation of indole for the production
      of secondary metabolites rather than tryptophan, thereby defining the branch
      point from primary to secondary metabolism. Bx2 through Bx5 encode cytochrome
      P450-dependent monooxygenases that catalyze four consecutive hydroxylations and
      one ring expansion to form the highly oxidized DIBOA.

PMID- 9235895
TI  - Formation, prevention, and repair of DNA damage by iron/hydrogen peroxide.

PMID- 9235896
TI  - A novel interaction between adrenergic receptors and the alpha-subunit of
      eukaryotic initiation factor 2B.
AB  - The alpha-subunit of eukaryotic initiation factor 2B (eIF-2B), a guanine
      nucleotide exchange protein that functions in regulation of translation, was
      observed to associate with the carboxyl-terminal cytoplasmic domains of the
      alpha2A- and alpha2B-adrenergic receptors in a yeast two-hybrid screen of a cDNA
      library prepared from 293 cells. This protein association was confirmed in vitro
      by affinity chromatography and was shown to be specific for a subset of G protein
      coupled receptors, including the alpha2A-, alpha2B-, alpha2C-, and beta2
      adrenergic receptors, but not the vasopressin (V2) receptor. Association of these
      proteins in vivo was confirmed by specific co-immunoprecipitation of eIF-2Balpha
      with full-length beta2-adrenergic receptors expressed in transfected 293 cells
      and by fluorescence microscopy showing co-localization of these proteins in
      intact cells. Remarkably, eIF-2Balpha co-localized with receptors exclusively in
      regions of the plasma membrane that are in contact with the extracellular medium,
      but failed to associate with membranes making cell-cell contacts. Overexpression
      of eIF-2Balpha in 293 cells caused a small (approximately 15%) but significant
      enhancement of beta2-adrenergic receptor-mediated activation of adenylyl cyclase,
      without affecting forskolin or V2 receptor-mediated activation. These
      observations suggest a new role for a previously identified guanine nucleotide
      exchange protein in membrane biology and cell signaling.

PMID- 9235897
TI  - A requirement for the mitogen-activated protein kinase cascade in hippocampal
      long term potentiation.
AB  - The mitogen-activated protein kinase (MAPK) cascade has been intensely studied as
      a primary biochemical pathway through which a variety of extracellular stimuli
      initiate and regulate processes of cellular transformation. That MAPKs are
      abundantly expressed in postmitotic neurons, however, suggests different yet
      currently unknown functions for this cascade in the mature nervous system. Here
      we report that the MAPK cascade is required for hippocampal long term
      potentiation (LTP), a robust and widely studied form of synaptic plasticity. We
      observed that PD 098059, a selective inhibitor of the MAPK cascade, blocked MAPK
      activation in response to direct stimulation of the NMDA receptor as well as to
      LTP-inducing stimuli. Furthermore, inhibition of the MAPK cascade markedly
      attenuated the induction of LTP. PD 098059, however, had no effect on the
      expression of established LTP, and the MAPK cascade was not persistently
      activated during LTP expression. Our observations provide the first demonstration
      of a role for the MAPK cascade in the activity-dependent modification of synaptic
      connections between neurons in the adult mammalian nervous system.

PMID- 9235898
TI  - The N-terminal extension of Galphaq is critical for constraining the selectivity
      of receptor coupling.
AB  - Characteristically, an individual member of the superfamily of G protein-coupled
      receptors can interact only with a limited number of the many structurally
      closely related G protein heterotrimers that are expressed within a cell.
      Interestingly, the N termini of two G protein alpha subunits, Galphaq and
      Galpha11, differ from those of other alpha subunits in that they display a
      unique, highly conserved six-amino acid extension. To test the hypothesis that
      this sequence element is critical for proper receptor recognition, we prepared a
      Galphaq deletion mutant (-6q) lacking these first six amino acids. The -6q
      construct (or wild type Galphaq as a control) was coexpressed (in COS-7 cells)
      with several different Gi/o- or Gs-coupled receptors, and ligand-induced
      increases in inositol phosphate production were determined as a measure of G
      protein activation. Whereas these receptors did not efficiently interact with
      wild type Galphaq, most of them gained the ability to productively couple to -6q.
      Additional experiments indicated that the observed functional promiscuity of -6q
      is not due to overexpression (as compared with wild type Galphaq) or to a lack of
      palmitoylation. We conclude that the N-terminal extension characteristic for
      Galphaq/11 proteins is critical for constraining the receptor coupling
      selectivity of these subunits, indicative of a novel mechanism by which the
      fidelity of receptor-G protein interactions can be regulated.

PMID- 9235899
TI  - Cloning and functional expression of a human kidney Na+:HCO3- cotransporter.
AB  - Several modes of HCO3- transport occur in the kidney, including Na+-independent
      Cl/HCO3- exchange (mediated by the AE family of Cl-/HCO3- exchangers), sodium
      dependent Cl-/HCO3- exchange, and Na+:HCO3- cotransport. The functional
      similarities between the Na+-coupled HCO3- transporters and the AE isoforms (i.e.
      transport of HCO3- and sensitivity to inhibition by 4,4'-diisothiocyanatostilbene
      2,2'-disulfonic acid) suggested a strategy for cloning the other transporters
      based on structural similarity with the AE family. An expressed sequence tag
      encoding part of a protein that is related to the known anion exchangers was
      identified in the GenBankTM expressed sequence tag data base and used to design
      an oligonucleotide probe. This probe was used to screen a human kidney cDNA
      library. Several clones were identified, isolated, and sequenced. Two overlapping
      cDNA clones were spliced together to form a 7.6-kilobase cDNA that contained the
      entire coding region of a novel protein. Based on the deduced amino acid
      sequence, the cDNA encodes a protein with a Mr of 116,040. The protein has 29%
      identity with human brain AE3. Northern blot analysis reveals that the 7.6
      kilobase mRNA is highly expressed in kidney and pancreas, with detectable levels
      in brain. Functional studies in transiently transfected HEK-293 cells demonstrate
      that the cloned transporter mediates Na+:HCO3- cotransport.

PMID- 9235900
TI  - Insulin-like growth factor-I rapidly activates multiple signal transduction
      pathways in cultured rat cardiac myocytes.
AB  - In response to insulin-like growth factor-I (IGF-I), neonatal rat cardiac
      myocytes exhibit a hypertrophic response. The elucidation of the IGF-I signal
      transduction system in these cells remains unknown. We show here that cardiac
      myocytes present a single class of high affinity receptors (12,446 +/- 3,669
      binding sites/cell) with a dissociation constant of 0.36 +/- 0.10 nM. Two
      different beta-subunits of IGF-I receptor were detected, and their
      autophosphorylation was followed by increases in the phosphotyrosine content of
      extracellular signal-regulated kinases (ERKs), insulin receptor substrate 1,
      phospholipase C-gamma1, and phosphatidylinositol 3-kinase. IGF-I transiently
      activates c-Raf in cultured neonatal cardiac myocytes, whereas A-raf is activated
      much less than c-Raf. Two peaks of ERK activity (ERK1 and ERK2) were resolved in
      cardiac myocytes treated with IGF-I by fast protein liquid chromatography, both
      being stimulated by IGF-I (with EC50 values for the stimulation of ERK1 and ERK2
      by IGF-I of 0.10 and 0. 12 nM, respectively). Maximal activation of ERK2 (12
      fold) and ERK1 (8.3-fold) activities was attained after a 5-min exposure to IGF
      I. Maximal activation of p90 S6 kinase by IGF-I was achieved after 10 min, and
      then the activity decreased slowly. Interestingly, IGF-I stimulates incorporation
      of [3H]phenylalanine (1.6-fold) without any effect on [3H]thymidine
      incorporation. These data suggest that IGF-I activates multiple signal
      transduction pathways in cardiac myocytes some of which may be relevant to the
      hypertrophic response of the heart.

PMID- 9235901
TI  - Ras-dependent mitogen-activated protein kinase activation by G protein-coupled
      receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin,
      Pyk2, and Src kinase.
AB  - Many receptors that couple to heterotrimeric guanine-nucleotide binding proteins
      (G proteins) have been shown to mediate rapid activation of the mitogen-activated
      protein kinases Erk1 and Erk2. In different cell types, the signaling pathways
      employed appear to be a function of the available repertoire of receptors, G
      proteins, and effectors. In HEK-293 cells, stimulation of either alpha1B- or
      alpha2A-adrenergic receptors (ARs) leads to rapid 5-10-fold increases in Erk1/2
      phosphorylation. Phosphorylation of Erk1/2 in response to stimulation of the
      alpha2A-AR is effectively attenuated by pretreatment with pertussis toxin or by
      coexpression of a Gbetagamma subunit complex sequestrant peptide (betaARK1ct) and
      dominant-negative mutants of Ras (N17-Ras), mSOS1 (SOS-Pro), and Raf (DeltaN
      Raf). Erk1/2 phosphorylation in response to alpha1B-AR stimulation is also
      attenuated by coexpression of N17-Ras, SOS-Pro, or DeltaN-Raf, but not by
      coexpression of betaARK1ct or by pretreatment with pertussis toxin. The alpha1B-
      and alpha2A-AR signals are both blocked by phospholipase C inhibition,
      intracellular Ca2+ chelation, and inhibitors of protein-tyrosine kinases.
      Overexpression of a dominant-negative mutant of c-Src or of the negative
      regulator of c-Src function, Csk, results in attenuation of the alpha1B-AR- and
      alpha2A-AR-mediated Erk1/2 signals. Chemical inhibitors of calmodulin, but not of
      PKC, and overexpression of a dominant-negative mutant of the protein-tyrosine
      kinase Pyk2 also attenuate mitogen-activated protein kinase phosphorylation after
      both alpha1B- and alpha2A-AR stimulation. Erk1/2 activation, then, proceeds via a
      common Ras-, calcium-, and tyrosine kinase-dependent pathway for both Gi- and
      Gq/11-coupled receptors. These results indicate that in HEK-293 cells, the
      Gbetagamma subunit-mediated alpha2A-AR- and the Galphaq/11-mediated alpha1B-AR
      coupled Erk1/2 activation pathways converge at the level of phospholipase C.
      These data suggest that calcium-calmodulin plays a central role in the calcium
      dependent regulation of tyrosine phosphorylation by G protein-coupled receptors
      in some systems.

PMID- 9235902
TI  - Cloning of a Chinese hamster ovary (CHO) cDNA encoding phosphatidylserine
      synthase (PSS) II, overexpression of which suppresses the phosphatidylserine
      biosynthetic defect of a PSS I-lacking mutant of CHO-K1 cells.
AB  - Phosphatidylserine (PtdSer) in mammalian cells is synthesized through the
      exchange of free L-serine for the polar head group (base) of preexisting
      phospholipid. We previously showed the presence of two different enzymes
      catalyzing the serine base exchange in Chinese hamster ovary (CHO) cells and
      isolated the cDNA of one of the enzymes, PtdSer synthase (PSS) I, which also
      catalyzes the exchange of the base moiety of phospholipid(s) for ethanolamine and
      choline. In this study, we cloned a CHO cDNA, designated as pssB, which encodes a
      protein exhibiting 32% amino acid sequence identity with CHO PSS I. Introduction
      of the pssB cDNA into CHO-K1 cells resulted in striking increases in both the
      serine and ethanolamine base exchange activities. In contrast to the PSS I cDNA,
      the pssB cDNA was incapable of increasing the choline base exchange activity. The
      expression of the pssB gene in Sf9 insect cells also results in striking
      increases in both serine and ethanolamine base exchange activities. The pssB cDNA
      was found to transform a PtdSer-auxotrophic PSS I-lacking mutant of CHO-K1 cells
      to PtdSer prototrophy. The PtdSer content of the resultant transformant grown
      without exogenous PtdSer for 2 days was 4-fold that of the mutant and similar to
      that of CHO-K1 cells, indicating that the pssB cDNA complemented the PtdSer
      biosynthetic defect of the PSS I-lacking mutant. These results suggested that the
      pssB cDNA encoded the second PtdSer synthase PSS II, which catalyzed the serine
      and ethanolamine base exchange, but not the choline base exchange.

PMID- 9235904
TI  - The oxidation of selenocysteine is involved in the inactivation of glutathione
      peroxidase by nitric oxide donor.
AB  - Glutathione peroxidase (GPx) was inactivated by S-nitroso-N-acetyl-D, L
      penicillamine (SNAP), a nitric oxide donor (Asahi, M., Fujii, J., Suzuki, K.,
      Seo, H. G., Kuzuya, T., Hori, M., Tada, M., Fujii, S., and Taniguchi, N. (1995)
      J. Biol. Chem. 270, 21035-21039). The structural basis of the inactivation was
      studied. We also show that 3-morpholinosydnonimine N-ethylcarbamide, a
      peroxynitrite precursor, as well as synthetic peroxynitrite also inactivated
      bovine GPx. The degree of incorporation of a sulfhydryl reagent, n
      octyldithionitrobenzoic acid, into GPx decreased after pretreatment with SNAP as
      evidenced by mass spectrometry. To identify the modification site of this enzyme
      by SNAP, both SNAP-pretreated and untreated GPxs were reacted with n
      octyldithionitrobenzoic acid and digested with lysylendopeptidase, and the
      resulting peptides were subjected to mass spectrometry. This technique identified
      a bridge between two peptides, one of which contains Sec45 at the catalytic
      center and Cys74, and the other contains Cys91. Although there are two possible
      combinations, selenocysteine 45 (Sec45) and Cys91 or Cys74 and Cys91, the
      tertiary structure of GPx indicates that a cross-link between Sec45 and Cys91 is
      more feasible. This is consistent with the experimental evidence that SNAP
      specifically inactivates GPx, in which Sec45 forms the catalytic center. Thus, we
      conclude that SNAP mainly oxidized Sec45 to form a selenenyl sulfide (Se-S) with
      a free thiol, leading to the inactivation of the enzyme. These data suggest that
      nitric oxide and its derivatives directly inactivate GPx in a specific manner via
      the production of a selenenyl sulfide, resulting in an increase in intracellular
      peroxides that are responsible for cellular damage.

PMID- 9235903
TI  - Novel regulation of the helix-loop-helix protein Id1 by S5a, a subunit of the 26
      S proteasome.
AB  - Id proteins negatively regulate the dimerization, DNA binding, and biological
      properties of basic helix-loop-helix proteins. In a search for novel factors that
      interact with Id1, we identified a component of the 26 S proteasome, S5a, that
      has previously been implicated only in the recognition of ubiquitinated
      polypeptides destined for proteolysis. S5a interacts strongly with Id1, less
      strongly with the basic helix-loop-helix proteins MyoD and E12, and not at all
      with other Id proteins. S5a restores DNA binding by MyoD-Id1 and E12-Id1
      heterodimers, enhances DNA binding by MyoD and E12 homodimers, and reverses Id1
      mediated repression of the muscle creatine kinase promoter during myogenic
      differentiation. Mutagenesis experiments showed that amino acids flanking the
      helix-loop-helix domain plus three residues in the first helix of Id1 impart S5a
      recognition. This requires only the NH2-terminal half of S5a. S5a thus appears to
      promote the positive regulation of myogenic genes through ubiquitin-independent
      mechanisms involving inhibition of Id1 and the enhancement of DNA binding by MyoD
      and E12. This latter property may permit the selection of novel promoter binding
      sites during myogenesis.

PMID- 9235905
TI  - Structure/function relationship of the cAMP response element in tyrosine
      hydroxylase gene transcription.
AB  - Expression of tyrosine hydroxylase (TH) is limited to catecholamine-producing
      neurons and neuroendocrine cells in a cell type-specific manner and is inducible
      by the cAMP-regulated signaling pathway. Previous results indicated that the cAMP
      response element (CRE) residing at -45 to -38 base pairs upstream of the
      transcription initiation site is essential for both basal and cAMP-inducible
      promoter activity of the 2.4-kilobase or shorter upstream sequence of the TH gene
      (Kim, K. S., Lee, M. K., Carroll, J. , and Joh, T. H. (1993) J. Biol. Chem. 268,
      15689-15695; Lazaroff, M. , Patankar, S., Yoon, S. O., and Chikaraishi, D. M.
      (1995) J. Biol. Chem. 270, 21579-21589). Here, we further report that the CRE is
      critical for the promoter activity of the 5.6- or 9.0-kilobase upstream sequences
      of the rat TH gene, which had been shown to direct the cell-specific TH
      expression in vivo. To define the structure/function relationship of the CRE in
      transcriptional activation of the TH gene, we performed saturated mutational
      analyses of 12 nucleotides encompassing the CRE. Mutation of any nucleotide
      within the octamer motif results in a significant decrease of both basal and cAMP
      inducible transcriptional activity of the TH reporter gene construct. Among the
      four nucleotides adjacent to the CRE (two 5' and two 3'), only the G residue at
      the immediate 3' position is important for full transcriptional activity. DNase I
      footprint analysis indicates a positive correlation between in vivo promoter
      activity and in vitro interaction between the CRE motif and its cognate protein
      factor(s). Reconstruction experiments using a TH promoter in which the native CRE
      was rendered inactive show that the CRE can transactivate transcription in either
      orientation through a window of approximately 200 base pairs upstream of the
      transcription initiation site, suggesting that CRE supports transcriptional
      activation of the TH gene in a distance-dependent manner. Finally, when the
      distance between the CRE and TATA box was changed by inserting an additional 5 or
      10 bases, it was observed that both insertional mutations increased activity by
      approximately 3-fold. The cAMP inducibility was as intact as the wild type
      construct. Together, these results are consistent with a model in which
      transcriptional activation of the TH gene by the CRE requires that it be located
      within a certain proximity of the CAP site but does not depend on a stringent
      stereospecific alignment in relationship to the TATA element.

PMID- 9235906
TI  - Isolation and characterization of a thiamin transport gene, THI10, from
      Saccharomyces cerevisiae.
AB  - We isolated a thiamin transporter gene, THI10, from a genomic library of
      Saccharomyces cerevisiae by the complementation of a yeast mutant defective in
      thiamin transport activity. The THI10 gene contained an open reading frame of
      1,794 base pairs encoding a 598-amino acid polypeptide with a calculated
      molecular weight of 66, 903. The nucleotide sequence of THI10 is completely
      identical to that of an anonymous DNA (open reading frame L8083.2) mapped to
      chromosome XII; two other genes (open reading frames YOR071c and YOR192c) in
      chromosome XV are extremely similar to THI10. Moreover, the THI10 gene product
      showed significant sequence homology with yeast allantoin and uracil
      transporters. Hydropathy profile suggested that THI10 product is highly
      hydrophobic and contains many transmembrane regions. Gene disruption of the THI10
      locus completely abolished the thiamin transport activity and thiamin binding
      activity in yeast plasma membrane fraction. Both the transport and thiamin
      binding activities were restored in the disrupted cells when the THI10 open
      reading frame was expressed by yeast GAL1 promoter, suggesting that the THI10
      gene encodes for the thiamin transport carrier protein. Northern blot analysis
      demonstrated that THI10 gene expression is regulated at the mRNA level by
      intracellular thiamin pyrophosphate and that it requires a positive regulatory
      factor encoded by THI3 gene.

PMID- 9235907
TI  - Defects in auxiliary redox proteins lead to functional methionine synthase
      deficiency.
AB  - Methionine synthase catalyzes a methyl transfer reaction from
      methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate
      and is dependent on methylcobalamin, a derivative of vitamin B12, for activity.
      Due to the lability of the intermediate, cob(I)alamin, the activity of methionine
      synthase is additionally dependent on a redox activation system. In bacteria, two
      flavoproteins, NADPH-flavodoxin reductase and flavodoxin, shuttle electrons from
      NADPH to methionine synthase. Their mammalian counterparts are unknown, and a
      putative intrinsic thiol oxidase activity of the mammalian methionine synthase
      has been proposed to be involved. We demonstrate that the mammalian methionine
      synthase can be activated in an NADPH-dependent reaction and requires a minimum
      of two redox proteins. This model is consistent with our results from biochemical
      complementation studies between cblG and cblE cell lines and mutation detection
      analysis in cblG cell lines. These demonstrate that the cblG cell line has
      defects affecting methionine synthase directly, whereas the cblE cell line has
      defects in the redox proteins. We have also identified a P1173L mutation in the
      activation domain of methionine synthase in the cblG cell line WG1505.

PMID- 9235908
TI  - Cloning, yeast expression, and characterization of the coupling of two distantly
      related Arabidopsis thaliana NADPH-cytochrome P450 reductases with P450 CYP73A5.
AB  - Two NADPH-cytochrome P450 reductase-encoding cDNAs were isolated from an
      Arabidopsis cDNA library by metabolic interference in a Saccharomyces cerevisiae
      mutant disrupted for its endogenous cpr1 gene. ATR1 encodes a protein of 692
      amino acids, while ATR2 encodes either a 712-residue protein (ATR2-1), or a 702
      residue protein (ATR2-2) depending on the choice of the initiation codon.
      Comparative analysis of ATR1 and ATR2-1 indicates 64% amino acid sequence
      identity and the absence of conservation in the third base of conserved amino
      acid codons. The two Arabidopsis reductases are encoded by distinct genes whose
      divergence is expected an early event in angiosperms evolution. A poly(Ser/Thr)
      stretch reminiscent of a plant chloroplastic targeting signal is present at the
      ATR2-1 N-terminal end but absent in ATR1. The cDNA open reading frames were
      expressed in yeast. The recombinant polypeptides were found present in the yeast
      endoplasmic reticulum membrane and exhibited a high specific NADPH-cytochrome c
      reductase activity. To gain more insight into the respective functions of the two
      reductases, the Arabidopsis cDNA encoding cinnamate 4-hydroxylase (CYP73A5) was
      cloned and co-expressed with ATR1 or ATR2 in yeast. Biochemical characterization
      of the Arabidopsis ATR1/CYP73A5 and ATR2-1/CYP73A5 systems demonstrates that the
      two distantly related Arabidopsis reductases similarly support the first
      oxidative step of the phenylpropanoid general pathway.

PMID- 9235909
TI  - Activation of RNase L by 2',5'-oligoadenylates. Biophysical characterization.
AB  - Ribonuclease L (RNase L) is an endoribonuclease that is activated upon binding of
      adenosine oligomers linked 2' to 5' to cleave viral and cellular RNAs. We
      recently proposed a model for activation in which activator A binds to monomer,
      E, to form EA, which subsequently dimerizes to the active form, E2A2 (Cole, J.
      L., Carroll, S. S., and Kuo, L. C. (1996) J. Biol. Chem. 271, 3978-3981). Here,
      we have employed this model to define the equilibrium constants for activator
      binding (Ka) and dimerization of EA to E2A2 (Kd) by equilibrium analytical
      ultracentrifugation and fluorescence measurements. Multi-wavelength sedimentation
      data were globally fit to the model above, yielding values of Ka = 1.69 microM
      and Kd = 17. 8 nM for 2',5'-linked adenosine trimer. Fluorescent conjugates of
      2',5'-linked adenosine trimer with 7-hydroxycoumarin have been prepared. The
      coumarin emission anisotropy shows a large increases upon binding to RNase L.
      Analysis of anisotropy titrations yields values of Ka and Kd close to those
      obtained by sedimentation. The sedimentation parameters for unmodified 2',5'
      linked adenosine trimer also agree with those obtained by enzyme kinetic methods
      (Carroll, S. S., Cole, J. L., Viscount, T., Geib, J., Gehman, J., and Kuo, L. C.
      (1997) J. Biol. Chem. 272, 19193-19198). Thus, the data presented here clearly
      define the energetics of RNase L activation and support the minimal activation
      model.

PMID- 9235910
TI  - Activation of RNase L by 2',5'-oligoadenylates. Kinetic characterization.
AB  - Ribonuclease L (RNase L), the 2',5'-oligoadenylate-dependent ribonuclease, is one
      of the cellular antiviral systems with enhanced activity in the presence of
      interferon. A reaction scheme has been developed to model the sequence of steps
      necessary for the activation of RNase L (Cole, J. L., Carroll, S. S., Blue, E.
      S., Viscount, T., and Kuo, L. C. (1997) J. Biol. Chem. 272, 19187-19192). The
      model comprises three sequential binding steps: the binding of activator to
      enzyme monomer, the subsequent dimerization of the activated monomer to form the
      active enzyme dimer, followed by the binding of substrate prior to catalysis. The
      model is used to evaluate the activation of RNase L by several synthetic analogs
      of the native activator. The 5'-phosphate of the activator has been determined to
      be an important structural determinant for the efficient activation of RNase L,
      and its loss caused a loss of activator affinity of 2-3 orders of magnitude. The
      length of activator is not an important determinant of activator potency for the
      activator analogs examined. The specific activity of the enzyme under conditions
      of saturation of activator binding and complete dimerization of the activated
      monomers varies only by about a factor of 3 for the activators examined,
      indicating that once dimerized in the presence of any of these activators, the
      enzyme exhibits a similar catalytic activity.

PMID- 9235911
TI  - Mitochondrial ubiquinone homologues, superoxide radical generation, and longevity
      in different mammalian species.
AB  - Rates of mitochondrial superoxide anion radical (O-2) generation are known to be
      inversely correlated with the maximum life span potential of different mammalian
      species. The objective of this study was to understand the possible mechanism(s)
      underlying such variations in the rate of O-2 generation. The hypothesis that the
      relative amounts of the ubiquinones or coenzyme Q (CoQ) homologues, CoQ9 and
      CoQ10, are related with the rate of O-2 generation was tested. A comparison of
      nine different mammalian species, namely mouse, rat, guinea pig, rabbit, pig,
      goat, sheep, cow, and horse, which vary from 3.5 to 46 years in their maximum
      longevity, indicated that the rate of O-2 generation in cardiac submitochondrial
      particles (SMPs) was directly related to the relative amount of CoQ9 and
      inversely related to the amount of CoQ10, extractable from their cardiac
      mitochondria. To directly test the relationship between CoQ homologues and the
      rate of O-2 generation, rat heart SMPs, naturally containing mainly CoQ9 and cow
      heart SMPs, with high natural CoQ10 content, were chosen for
      depletion/reconstitution experiments. Repeated extractions of rat heart SMPs with
      pentane exponentially depleted both CoQ homologues while the corresponding rates
      of O-2 generation and oxygen consumption were lowered linearly. Reconstitution of
      both rat and cow heart SMPs with different amounts of CoQ9 or CoQ10 caused an
      initial increase in the rates of O-2 generation, followed by a plateau at high
      concentrations. Within the physiological range of CoQ concentrations, there were
      no differences in the rates of O-2 generation between SMPs reconstituted with
      CoQ9 or CoQ10. Only at concentrations that were considerably higher than the
      physiological level, the SMPs reconstituted with CoQ9 exhibited higher rates of O
      2 generation than those obtained with CoQ10. These in vitro findings do not
      support the hypothesis that differences in the distribution of CoQ homologues are
      responsible for the variations in the rates of mitochondrial O-2 generation in
      different mammalian species.

PMID- 9235912
TI  - Cell adhesion to a motif shared by the malaria circumsporozoite protein and
      thrombospondin is mediated by its glycosaminoglycan-binding region and not by
      CSVTCG.
AB  - The malaria circumsporozoite protein (CS), thrombospondin (TSP), and several
      other proteins including the terminal complement proteins and the neural adhesion
      molecules F-spondin and Unc-5, share a cell adhesive sequence. In CS this
      sequence is designated as region II-plus (EWSPCSVTCGNGIQVRIK) and in TSP it is
      found in the type I repeats. Previous studies aimed at fine mapping the amino
      acid residues required for cell adhesion have yielded discrepant results. Here we
      show in three different cell lines that the downstream basic residues are
      required for cell adhesion whereas the CSVTCG sequence is not. Using mutant
      Chinese hamster ovary cells selected for deficiencies in proteoglycan synthesis,
      we show that in wild type cells, heparan sulfate proteoglycans are the binding
      sites for this motif. This finding is supported by additional experiments with
      two other cell lines demonstrating that treatment with heparitinase but not
      chondroitinase abolishes cell adhesion to peptides representing this motif. Using
      Chinese hamster ovary cell mutants deficient in heparan sulfate proteoglycans but
      possessing chondroitin sulfate proteoglycans, we show that cell surface
      chondroitin sulfate proteoglycans can also mediate binding to this motif although
      higher concentrations of peptides are required for adhesion. Chondroitinase, but
      not heparitinase, treatment of these cells destroys cell surface-binding sites.
      Taken together, these results indicate that cell adhesion to this motif involves
      an interaction between the downstream positively-charged residues and the
      negatively charged glycosaminoglycan chains of heparan sulfate, or in some cases
      chondroitin sulfate, proteoglycans on the cell surface.

PMID- 9235913
TI  - Activation, inhibition, and regiospecificity of the lysophospholipase activity of
      the 85-kDa group IV cytosolic phospholipase A2.
AB  - The 85-kDa Group IV calcium-dependent cytosolic phospholipase A2 (cPLA2)
      catalyzes the hydrolysis of palmitoylglycero-3-phosphocholine to palmitic acid
      and glycero-3-phosphocholine. Palmitoylglycero-3-phosphocholine exists as a 9:1
      equilibrium mixture of the sn-1 and sn-2 isomers, with the fatty acid
      predominately at the sn-1 position. We have monitored this reaction by 31P NMR to
      determine which palmitoylglycero-3-phosphocholine isomer is processed by cPLA2.
      When both lysophospholipid isomers are present in a 1:1 mixture under conditions
      in which acyl migration is minimized, cPLA2 rapidly consumes both isomers.
      However, 1-palmitoylglycero-3-phosphocholine is consumed seven times faster than
      the 2-palmitoylglycero-3-phosphocholine isomer. We have previously reported that
      this lysophospholipase reaction is accelerated in the presence of glycerol. We
      now find that this apparent increase in activity is accounted for, in part, by
      glycerol acting as an alternative acceptor for the cleaved fatty acid, as is the
      case for this enzyme's phospholipase A2 (PLA2) activity. In contrast,
      dioleoylglycerol, which accelerates the PLA2 activity, does not act as an
      acceptor in either the lysophospholipase or the PLA2 reaction, but can affect
      enzyme activities by altering substrate presentation. We also show that a known
      inhibitor of the PLA2 activity of cPLA2 is able to inhibit its lysophospholipase
      activity with a similar IC50 to its PLA2 activity. However, the effect of
      inhibitors is dependent on the manner in which they are presented to the enzyme.

PMID- 9235914
TI  - Structure and organization of the human ankyrin-1 gene. Basis for complexity of
      pre-mRNA processing.
AB  - Ankyrin-1 (ANK-1) is an erythrocyte membrane protein that is defective in many
      patients with hereditary spherocytosis, a common hemolytic anemia. In the red
      cell, ankyrin-1 provides the primary linkage between the membrane skeleton and
      the plasma membrane. To gain additional insight into the structure and function
      of this protein and to provide the necessary tools for further genetic studies of
      hereditary spherocytosis patients, we cloned the human ANK-1 chromosomal gene.
      Characterization of the ANK-1 gene genomic structure revealed that the erythroid
      transcript is composed of 42 exons distributed over approximately 160 kilobase
      pairs of DNA. Comparison of the genomic structure with the protein domains
      reveals a near-absolute correlation between the tandem repeats encoding the
      membrane-binding domain of ankyrin with the location of the intron/exon
      boundaries in the corresponding part of the gene. Erythroid stage-specific,
      complex patterns of alternative splicing were identified in the region encoding
      the regulatory domain of ankyrin-1. Novel brain-specific transcripts were also
      identified in this region, as well as in the "hinge" region between the membrane
      binding and spectrin-binding domains. Utilization of alternative polyadenylation
      signals was found to be the basis for the previously described, stage-specific
      9.0- and 7.2-kilobase pair transcripts of the ANK-1 gene.

PMID- 9235915
TI  - A kinetic model for the binding of Ca2+ to the regulatory site of troponin from
      cardiac muscle.
AB  - The kinetics of the binding of Ca2+ to the single regulatory site of cardiac
      muscle troponin was investigated by using troponin reconstituted from the three
      subunits, using a monocysteine mutant of troponin C (cTnC) labeled with the
      fluorescent probe 2-[(4'-(iodoacetamido)anilino]naphthalene-6-sulfonic acid
      (IAANS) at Cys-35. The kinetic tracings of binding experiments for troponin
      determined at free [Ca2+] > 1 microM were resolved into two phases. The rate of
      the fast phase increased with increasing [Ca2+], reaching a maximum of about 35 s
      1 at 4 degrees C, and the rate of the slow phase was approximately 5 s-1 and did
      not depend on [Ca2+]. Dissociation of bound Ca2+ occurred in two phases, with
      rates of about 23 and 4 s-1. The binding and dissociation results obtained with
      the binary complex formed between cardiac troponin I and the IAANS-labeled cTnC
      mutant were very similar to those obtained from reconstituted troponin. The
      kinetic data are consistent with a three-step sequential model similar to the
      previously reported mechanism for the binding of Ca2+ to a cTnC mutant labeled
      with the same probe at Cys-84 (Dong et al. (1996) J. Biol. Chem. 271, 688-694).
      In this model, the initial binding in the bimolecular step to form the Ca2+
      troponin complex is assumed to be a rapid equilibrium, followed by two sequential
      first-order transitions. The apparent bimolecular rate constant is 5.1 x 10(7) M
      1 s-1, a factor of 3 smaller than that for cTnC. The rates of the first-order
      transitions are an order of magnitude smaller for troponin than for cTnC. These
      kinetic differences form a basis for the enhanced Ca2+ affinity of troponin
      relative to the Ca2+ affinity of isolated cTnC. Phosphorylation of the
      monocysteine mutant of troponin I by protein kinase A resulted in a 3-fold
      decrease in the bimolecular rate constant but a 2-fold increase in the two
      observed Ca2+ dissociation rates. These changes in the kinetic parameters are
      responsible for a 5-fold reduction in Ca2+ affinity of phosphorylated troponin
      for the specific site.

PMID- 9235916
TI  - p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that
      associates with p85 and is expressed predominantly in leukocytes.
AB  - We have identified a novel p110 isoform of phosphatidylinositol 3-kinase from
      human leukocytes that we have termed p110delta. In addition, we have
      independently isolated p110delta from a mouse embryo library on the basis of its
      ability to interact with Ha-RasV12 in the yeast two-hybrid system. This unique
      isoform contains all of the conserved structural features characteristic of the
      p110 family. Recombinant p110delta phosphorylates phosphatidylinositol and
      coimmunoprecipitates with p85. However, in contrast to previously described p110
      subunits, p110delta is expressed in a tissue-restricted fashion; it is expressed
      at high levels in lymphocytes and lymphoid tissues and may therefore play a role
      in phosphatidylinositol 3-kinase-mediated signaling in the immune system.

PMID- 9235917
TI  - Signal transduction via glycosyl phosphatidylinositol-anchored proteins in T
      cells is inhibited by lowering cellular cholesterol.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins can deliver costimulatory
      signals to lymphocytes, but the exact pathway of signal transduction involved is
      not yet characterized. GPI-anchored proteins are fixed to the cell surface solely
      by a phospholipid moiety and are clustered in distinct membrane domains that are
      formed by an unique lipid composition requiring cholesterol. To elucidate the
      role of membrane lipids for signal transduction via GPI-anchored proteins, we
      studied the influence of reduced cellular cholesterol content on calcium
      signaling via GPI-anchored CD59 and CD48 in Jurkat T cells. Lowering cholesterol
      by different inhibitors of cellular cholesterol synthesis suppressed calcium
      response via GPI-anchored proteins by about 50%, whereas stimulation via CD3 was
      only minimally affected (<10%). The decrease in overall calcium response via GPI
      anchored proteins was reflected by inhibition of calcium release from
      intracellular stores. Cell surface expression of GPI-anchored proteins was not
      changed quantitatively by lowering cellular cholesterol, and neither was the
      pattern of immunofluorescence in microscopic examination. In addition, the
      distribution of GPI-anchored proteins in detergent-insoluble complexes remained
      unaltered. These results suggest that cellular cholesterol is an important
      prerequisite for signal transduction via GPI-anchored proteins beyond formation
      of membrane domains.

PMID- 9235918
TI  - Proteolysis of platelet cortactin by calpain.
AB  - Cortactin, a substrate of pp60(c-)src and a potent filamentous actin binding and
      cross-linking protein, is abundant in circulating platelets. After stimulation of
      platelet aggregation with collagen, cortactin undergoes a dramatic increase in
      tyrosine phosphorylation followed by a rapid degradation. The cleavage of
      platelet cortactin was detected in lysates prepared using either Triton
      containing buffer or SDS-sample buffer. However, the degradation of cortactin was
      not observed in platelets derived from a Glanzmann's patient, who lacked
      functional integrin alphaIIbbeta3 (GPIIb-IIIa). In addition, the proteolysis of
      cortactin was abolished by treating platelets before but not after collagen
      stimulation with EGTA or calpeptin. Furthermore, recombinant cortactin was
      digested by mu-calpain in vitro in a dose-dependent manner, indicating that
      cortactin is a substrate for calpain. We also observed that the calpain-mediated
      digestion in vitro is dependent on the presence of a sequence containing a
      proline-rich region and multiple tyrosine residues that are phosphorylated by
      pp60(c-)src. Tyrosine phosphorylation by pp60(c-)src up-regulates the activity of
      calpain toward cortactin. Our data suggest that the calpain-mediated proteolysis
      of tyrosine-phosphorylated cortactin may provide a mechanism to remodel
      irreversibly the cytoskeleton in response to platelet agonists.

PMID- 9235919
TI  - Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha.
      Modulation of transcriptional activity by oxygen tension.
AB  - Hypoxia-inducible factor 1 (HIF-1) binds to cis-acting hypoxia-response elements
      within the erythropoietin, vascular endothelial growth factor, and other genes to
      activate transcription in hypoxic cells. HIF-1 is a basic helix-loop-helix
      transcription factor composed of HIF-1alpha and HIF-1beta subunits. Here, we
      demonstrate that HIF-1alpha contains two transactivation domains located between
      amino acids 531 and 826. When expressed as GAL4 fusion proteins, the
      transcriptional activity of these domains increased in response to hypoxia.
      Fusion protein levels were unaffected by changes in cellular O2 tension. Two
      minimal transactivation domains were localized to amino acid residues 531-575 and
      786-826. The transcriptional activation domains were separated by amino acid
      sequences that inhibited transactivation. Deletion analysis demonstrated that the
      gradual removal of inhibitory domain sequences (amino acids 576-785) was
      associated with progressively increased transcriptional activity of the fusion
      proteins, especially in cells cultured at 20% O2. Transcriptional activity of
      GAL4/HIF-1alpha fusion proteins was increased in cells exposed to 1% O2, cobalt
      chloride, or desferrioxamine, each of which also increased levels of endogenous
      HIF-1alpha protein but did not affect fusion protein levels. These results
      indicate that increased transcriptional activity mediated by HIF-1 in hypoxic
      cells results from both increased HIF-1alpha protein levels and increased
      activity of HIF-1alpha transactivation domains.

PMID- 9235920
TI  - The Listeria monocytogenes-secreted p60 protein is an N-end rule substrate in the
      cytosol of infected cells. Implications for major histocompatibility complex
      class I antigen processing of bacterial proteins.
AB  - Cytosolic antigen degradation is an initial step in the generation of major
      histocompatibility complex (MHC) class I-associated cytolytic T lymphocyte
      epitopes. Intracellular Listeria monocytogenes secretes p60, a murein hydrolase,
      into the host cell cytosol, where it is degraded by proteasomes. Roughly 3% of
      degraded p60 gives rise to p60 217-225, a nonamer peptide that is bound by H-2Kd
      MHC class I molecules. Herein, we introduce targeted deletions throughout the p60
      gene to identify potential proteolytic signals within p60. Degradation of mutant
      forms of p60 was investigated in macrophages infected with recombinant L.
      monocytogenes. We found that deletions within the amino-terminal two-thirds of
      p60 enhanced cytosolic degradation. In contrast, truncation of the C terminus
      resulted in modest stabilization of p60 in the host cell cytosol. Because a
      protein's N-terminal amino acid can determine its rate of degradation, we
      mutagenized this residue in p60 into known stabilizing and destabilizing
      residues. Valine substitution dramatically stabilized cytosolic p60 molecules,
      while substitution with aspartic acid resulted in rapid degradation. The number
      of p60 217-225 epitopes isolated from infected cells directly correlated with the
      rates of p60 degradation. Our data, therefore, indicate that the N-terminal amino
      acid and multiple internal regions of p60 influence its stability in the cytosol
      of infected cells. Antigen degradation and epitope generation are linked, and
      different degradation signals can channel bacterial proteins into the MHC class I
      antigen processing pathway.

PMID- 9235921
TI  - The linoleic acid metabolite, (13S)-hydroperoxyoctadecadienoic acid, augments the
      epidermal growth factor receptor signaling pathway by attenuation of receptor
      dephosphorylation. Differential response in Syrian hamster embryo tumor
      suppressor phenotypes.
AB  - In Syrian hamster embryo (SHE) fibroblasts, epidermal growth factor receptor
      (EGFR) tyrosine kinase activity regulates the metabolism of endogenous linoleic
      acid to (13S)-hydroperoxyoctadecadienoic acid (13S)-HPODE). (13S)-HPODE
      stimulates EGF-dependent mitogenesis in a SHE cell phenotype, which expresses
      tumor suppressor genes (supB+), but was not effective in a variant that does not
      express these suppressor genes (supB-). In the present study, we have
      investigated the potential effects of this lipid metabolite on the EGFR signaling
      pathways in these two SHE cell lines. Treatment of quiescent SHE cells with EGF
      produced a rapid, transient increase in the tyrosine phosphorylation of EGFR.
      Dependence on EGF concentration for EGFR tyrosine phosphorylation was similar in
      both SHE cell lines, but a more prolonged phosphorylation was detected in the
      supB- variant. Incubation of supB+ cells with (13S)-HPODE and EGF increased EGFR
      autophosphorylation and tyrosine phosphorylation on several signaling proteins
      with Src homology-2 domains including GTPase-activating protein. The lipid
      metabolite did not significantly alter EGF-dependent tyrosine phosphorylation in
      the supB- variant. Tyrosine phosphorylation of mitogen-activated protein (MAP)
      kinase was also measured. The addition of (13S)-HPODE increased the extent and
      duration of MAP kinase tyrosine phosphorylation in supB+ cells but not in the
      supB- variant. MAP kinase activity in supB+ cells, as measured in
      immunoprecipitates from cells after the addition of EGF, was increased by the
      presence of (13S)-HPODE. The addition of (13S)-HPODE did not directly alter EGFR
      kinase activity or the internalization of the EGFR. However, the addition of
      (13S)-HPODE to supB+ cells extended the tyrosine phosphorylation of the EGFR in
      response to EGF. The dephosphorylation of the EGFR was measured directly, and a
      slower rate was observed in the supB- compared with the supB+ cells. Incubation
      of the supB+ cells with (13S)-HPODE attenuated the dephosphorylation of the EGFR.
      Thus, (13S)-HPODE stimulates EGF-dependent mitogenesis and up-regulation of EGF
      dependent tyrosine phosphorylation by inhibiting the dephosphorylation of the
      EGFR. This study shows that a metabolite of an essential dietary fatty acid,
      linoleic acid, can modulate tyrosine phosphorylation and activity of key signal
      transduction proteins in a growth factor mitogenic pathway.

PMID- 9235922
TI  - Effect of metal on 2,4,5-trihydroxyphenylalanine (topa) quinone biogenesis in the
      Hansenula polymorpha copper amine oxidase.
AB  - Previous studies of wild-type and mutant forms of a recombinant copper amine
      oxidase from Hansenula polymorpha, expressed in Saccharomyces cerevisiae, have
      indicated a self-processing mechanism for 2,4,5-trihydroxyphenylalanine (topa)
      quinone biogenesis involving the active site copper (Cai, D., and Klinman, J. P.
      (1994) J. Biol. Chem. 269, 32039-32042). In contrast to prokaryotic copper amine
      oxidases, however, it has not been possible to initiate topa quinone formation by
      the addition of exogenous copper to precursor H. polymorpha amine oxidase lacking
      copper. Metal analysis of copper-depleted wild-type enzyme reveals 0.2-0.3 mol
      copper, together with 0.6 mol zinc. Despite changes in the zinc and copper levels
      in growth media, the level of zinc in purified enzyme remains fairly constant.
      Further, we have been unable to displace protein-bound zinc by exogenously added
      copper. The H. polymorpha amine oxidase gene was subsequently expressed in
      Escherichia coli and found to be almost completely free of copper and zinc. In
      vitro reconstitution of this apoprotein confirms that zinc binds to H. polymorpha
      amine oxidase and prevents reconstitution with copper. By contrast, addition of
      copper first to apoprotein leads to formation of topa quinone and stable activity
      in the presence of added zinc. These findings indicate efficient binding of
      either zinc or copper to a site that undergoes little or no exchange. The data
      confirm that topa quinone biogenesis in the H. polymorpha system is catalyzed by
      copper and occurs in the absence of added factors. We conclude that the
      mechanisms of cofactor biogenesis in pro- and eukaryotic systems are likely to be
      similar or identical. The results described herein imply different pathways for
      the in vivo assembly of heterologously expressed amine oxidases in S. cerevisiae
      and E. coli.

PMID- 9235923
TI  - 108-pS channel in brown fat mitochondria might Be identical to the inner membrane
      anion channel.
AB  - Single-channel and whole-mitoplast patch-clamp recordings were employed to
      characterize the 108-pS (Cl-) channel in brown fat mitochondrial mitoplasts. We
      demonstrated the ability of this channel to conduct di- and trivalent anions,
      such as sulfate, phosphate, and benzenetricarboxylates, and its blockage by
      propranolol, 1,4-dihydropyridine-type Ca2+ antagonists, and Cibacron blue.
      Moreover, we have revealed its pH dependence for the first time. As a basis for
      the characteristic potential dependence of the whole-mitoplast current, we
      identified an open probability, increasing with depolarizing (positive)
      potentials, Eh, and being almost zero in the hyperpolarizing range. Events at
      negative Eh exhibit a short flickering behavior, whereas at positive Eh, they
      become much longer. This voltage dependence is influenced by pH in such a way
      that, at acidic pH, the 108-pS channel possesses a low open probability
      throughout the observed potential range, whereas at alkaline pH, the channel
      switches to long openings, even at a negative potential. All these properties
      lead us to conclude that the inner membrane anion channel, which has been
      characterized only by light scattering studies, and the 108-pS inner membrane
      channel, which has been characterized electrophysiologically, are one and the
      same process.

PMID- 9235924
TI  - Independence of two conformations of sarcoplasmic reticulum Ca2+-ATPase molecules
      in hydrolyzing acetyl phosphate. A two-pair model of the ATPase structural unit.
AB  - The sarcoplasmic reticulum Ca2+-ATPase molecules have been shown to exist in two
      conformations (A and B) that result from intermolecular interaction of ATPase
      molecules (Nakamura, J., and Tajima, G. (1995) J. Biol. Chem. 270, 17350-17354).
      The A form binds two calcium ions noncooperatively, whereas the B form binds the
      calcium ions cooperatively. Here, we examined the independence of these two forms
      in the calcium-activated hydrolysis of acetyl phosphate (AcP) under asynchronous
      and synchronous conditions of their E1-E2 transitions at 0-5 and 25 degrees C.
      Irrespective of their synchronism and temperature, the two forms hydrolyzed AcP
      due to calcium that was bound to each of the forms, indicating the independence
      of the two forms in hydrolyzing AcP. Taking into account the monomer-dimer
      transition of the ATPase molecules on the sarcoplasmic reticulum membrane
      accompanying E1-E2 transition of the molecules (Dux, L., Taylor, K. A., Ting
      Beall, H. P., and Martonosi, A. (1985) J. Biol. Chem. 260, 11730-11743), the two
      types of molecules seem to independently carry out such monomer-dimer transition
      of the same type of molecules. Two pairs, each consisting of the same type of
      molecules, are suggested to be the structural unit of the ATPase molecules.

PMID- 9235925
TI  - Conformational changes and stabilization induced by ligand binding in the DNA
      binding domain of the E2 protein from human papillomavirus.
AB  - We are investigating the folding of the 81-residue recombinant dimeric DNA
      binding domain of the E2 protein from human papillomavirus and how it is coupled
      to the binding of its DNA ligand. Modifications in buffer composition, such as
      ionic strength and phosphate, cause an approximately 5.0 kcal mol-1 stabilization
      of the domain to urea unfolding, based on very similar conformational changes as
      measured by far UV circular dichroism. Binding of DNA produces an even greater
      stabilization, magnitude similar to that caused by the nonspecific polymer ligand
      heparin, which shifts the urea midpoint 2.5-fold. The DNA-bound complex displays
      substantial changes similar to those caused by ionic strength and phosphate in
      terms of overall secondary structure. Bis-8-anilino-1-naphthalenesulfonate
      provides a very sensitive conformational probe, which shows alterations in the
      domain caused by the above mentioned compounds. In general terms, binding of DNA
      involves an overall conformational readjustment in the protein but maintains the
      beta-barrel scaffold intact. This conformational plasticity seems to be of
      importance in the regulatory functions of this type of DNA-binding protein. The
      extremely long half-life of the E2-DNA complex, together with its very high
      stability, suggests that, in the absence of other factors that may affect its
      stability in vivo, the possibility of dissociation once formed is restricted.

PMID- 9235926
TI  - AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1
      encoding a transporter of the major facilitator superfamily.
AB  - We have isolated a Candida albicans gene that confers resistance to the azole
      derivative fluconazole (FCZ) when overexpressed in Saccharomyces cerevisiae. This
      gene encodes a protein highly homologous to S. cerevisiae yAP-1, a bZip
      transcription factor known to mediate cellular resistance to toxicants such as
      cycloheximide (CYH), 4-nitroquinoline N-oxide (4-NQO), cadmium, and hydrogen
      peroxide. The gene was named CAP1, for C. albicans AP-1. Cap1 and yAP-1 are
      functional homologues, since CAP1 expression in a yap1 mutant strain partially
      restores the ability of the cells to grow on toxic concentrations of cadmium or
      hydrogen peroxide. We have found that the expression of YBR008c, an open reading
      frame identified in the yeast genome sequencing project and predicted to code for
      a multidrug transporter of the major facilitator superfamily, is dramatically
      induced in S. cerevisiae cells overexpressing CAP1. Overexpression of either CAP1
      or YAP1 in a wild-type strain results in resistance to FCZ, CYH, and 4-NQO,
      whereas such resistance is completely abrogated (FCZ and CYH) or strongly reduced
      (4-NQO) in a ybr008c deletion mutant, demonstrating that YBR008c is involved in
      YAP1- and CAP1-mediated multidrug resistance. YBR008c has been renamed FLR1, for
      fluconazole resistance 1. The expression of an FLR1-lacZ reporter construct is
      strongly induced by the overexpression of either CAP1 or YAP1, indicating that
      the FLR1 gene is transcriptionally regulated by the Cap1 and yAP-1 proteins.
      Taken collectively, our results demonstrate that FLR1 represents a new YAP1
      controlled multidrug resistance molecular determinant in S. cerevisiae. A similar
      detoxification pathway is also likely to operate in C. albicans.

PMID- 9235927
TI  - Chaperone SecB from Escherichia coli mediates kinetic partitioning via a dynamic
      equilibrium with its ligands.
AB  - We have shown that the complexes between SecB, a chaperone from Escherichia coli,
      and two physiological ligands, galactose-binding protein and maltose-binding
      protein, are in rapid, dynamic equilibrium between the bound and free states.
      Binding to SecB is readily reversible, and each time the ligand is released it
      undergoes a kinetic partitioning between folding to its native state and re
      binding to SecB. Binding requires that the polypeptide be devoid of tertiary
      structure; once the protein has folded, it is no longer a ligand. Conditions were
      established in which folding of the polypeptides was sufficiently slow so that at
      each cycle of dissociation rebinding was favored over folding and a kinetically
      stable complex between SecB and each polypeptide ligand was observed. Evidence
      that the ligand is continually released to the bulk solution and rebound was
      obtained by altering the conditions to increase the rate of folding of each
      ligand so that folding of the ligand was faster than reassociation with SecB
      thereby allowing the system to partition to free SecB and folded polypeptide
      ligand. We conclude that complexes between the chaperone SecB and ligands are in
      dynamic, rapid equilibrium with the free states. This mode of binding is simpler
      than that documented for chaperones that function to facilitate folding such as
      the Hsp70s and Hsp60s, where hydrolysis of ATP is coupled to the binding and
      release of ligands. This difference may reflect the fact that SecB does not
      mediate folding but is specialized to facilitate protein export. Without a
      requirement for exogenous energy it efficiently performs its sole duty: to keep
      proteins in a nonnative conformation and thus competent for export.

PMID- 9235928
TI  - Genes for Tfb2, Tfb3, and Tfb4 subunits of yeast transcription/repair factor IIH.
      Homology to human cyclin-dependent kinase activating kinase and IIH subunits.
AB  - Genes for the Tfb2, Tfb3, and Tfb4 subunits of yeast RNA polymerase transcription
      factor IIH (TFIIH) are described. All three genes are essential for cell
      viability, and antibodies against Tfb3 specifically inhibit transcription in
      vitro. A C-terminal deletion of Tfb2 caused a defect in nucleotide excision
      repair, as shown by UV sensitivity of the mutant strain and loss of nucleotide
      excision repair activity in cell extracts (restored by the addition of purified
      TFIIH). An interaction between Tfb3 and the Kin28 subunit of TFIIH was detected
      by the two-hybrid approach, consistent with a role for Tfb3 in linking kinase and
      core domains of the factor. The deduced amino acid sequence of Tfb2 is similar to
      that of the 52-kDa subunit of human TFIIH, while Tfb3 is identified as a RING
      finger protein homologous to the 36-kDa subunit of murine CAK (cyclin-dependent
      kinase activating kinase) and to the 32-kDa subunit of human TFIIH. Tfb4 is
      homologous to p34 of human TFIIH and is identified as the weakly associated 37
      kDa subunit of the yeast factor. These and other findings reveal a one-to-one
      correspondence and high degree of sequence similarity between the entire set of
      yeast and human TFIIH polypeptides.

PMID- 9235929
TI  - Activation of R-Ras GTPase by GTPase-activating proteins for Ras, Gap1(m), and
      p120GAP.
AB  - The enzymatic properties of Gap1(m) were characterized using three Ras and R-Ras
      proteins as substrates and were compared with those of p120GAP. Gap1(m)
      stimulated the GTPase of Ras better than that of R-Ras, in contrast to p120GAP
      which promoted the GTPase of R-Ras better than that of Ras. The EC50 values of
      Gap1(m) for Ha-Ras and R-Ras were 0.48 +/- 0.02 and 1.13 +/- 0.12 nM,
      respectively, whereas the EC50 values of p120GAP for Ha-Ras and R-Ras were 23.1
      +/- 1.9 and 3.86 +/- 0.38 nM, respectively. The affinities of Gap1(m) and p120GAP
      to the substrates determined by competitive inhibition by using Ha-Ras.GTPgammaS
      (guanosine 5'-O-(3-thiotriphosphate)) or R-Ras.GTPgammaS as a competitor agreed
      well with the substrate specificities of these GTPase-activating proteins. The Km
      values of Gap1(m) for Ha-Ras and R-Ras were 1.53 +/- 0.27 and 3.38 +/- 0.53
      microM, respectively, which were lower than that of p120GAP for Ha-Ras (145 +/-
      11 microM) by almost 2 orders of magnitude. The high affinity of Gap1(m) to the
      substrates and its membrane localization suggest that Gap1(m) may act as a
      regulator of the basal activity of Ha-Ras and R-Ras.

PMID- 9235930
TI  - A mammalian transient type K+ channel, rat Kv1.4, has two potential domains that
      could produce rapid inactivation.
AB  - The "ball and chain" model has been shown to be suitable for explaining the rapid
      inactivation of voltage-dependent K+ channels. For the Drosophila Shaker K+
      channel (ShB), the first 20 residues of the amino terminus have been identified
      as the inactivation ball that binds to the open channel pore and blocks ion flow
      (Hoshi, T., Zagotta, W. N., and Aldrich, R. W. (1990) Science 250, 533-538;
      Zagotta, W. N., Hoshi, T., and Aldrich, R. W. (1990) Science 250, 568-571). We
      studied the structural elements responsible for rapid inactivation of a mammalian
      transient type K+ channel (rat Kv1.4) by constructing various mutants in the
      amino terminus and expressing them in Xenopus oocytes. Although it has been
      reported that the initial 37 residues might form the inactivation ball for rat
      Kv1.4 (Tseng-Crank, J., Yao, J.-A., Berman M. F., and Tseng, G.-N. (1993) J. Gen.
      Physiol. 102, 1057-1083), we found that not only the initial 37 residues, but
      also the following region, residues 40-68, could function independently as an
      inactivation gate. Like the Shaker inactivation ball, both potential inactivation
      domains have a hydrophobic amino-terminal region and a hydrophilic carboxyl
      terminal region having net positive charge, which is essential for the domains to
      function as an inactivation gate.

PMID- 9235931
TI  - Cell adhesion to fibronectin regulates membrane lipid biosynthesis through 5'-AMP
      activated protein kinase.
AB  - We have shown that attachment to a fibronectin substrate stimulates two pathways
      of lipid biosynthesis in cultured human fibroblasts. Detachment of these cells
      (mechanically, with trypsin, or by RGDS peptides) caused a significant decrease
      in their 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and in their
      incorporation of [3H]acetate into fatty acids. This inhibition was substantially
      reversed by the reattachment of cells to fibronectin substrates, but not to poly
      L-lysine substrates or to fibronectin in solution. Inhibiting phosphoprotein
      phosphatase activity with okadaic acid blocked the recovery of both biosynthetic
      activities. Both 3-hydroxy-3-methylglutaryl-coenzyme A reductase and fatty acid
      biosynthesis are known to be inhibited by the action of 5'-AMP-activated protein
      kinase, which is activated by an increase in the level of AMP relative to ATP.
      For example, in our system, sodium azide and 2-deoxy-D-glucose increased the
      ratio of cellular AMP to ATP and caused a decrease in lipid biosynthesis. We then
      verified the prediction that detachment of cells from substrates also caused an
      increase in the AMP/ATP ratio. We therefore conclude that the attachment of cells
      to fibronectin promotes lipid biosynthesis, presumably in coordination with the
      cellular growth response evoked by attachment to the extracellular matrix.

PMID- 9235932
TI  - Structural and functional roles of tyrosine 78 of yeast guanylate kinase.
AB  - The hydroxyl group of Tyr-78 of yeast guanylate kinase (GK) is hydrogen-bonded to
      the phosphate of the bound GMP as revealed by x-ray crystallography. The
      structural and functional roles of Tyr-78 were evaluated by site-directed
      mutagenesis, kinetics, guanidine hydrochloride-induced denaturation, and nuclear
      magnetic resonance spectroscopy (NMR). Substitution of Tyr-78 with a
      phenylalanine resulted in a decrease in kcat by a factor of 131, an increase in
      Km(GMP) by a factor of 20 and an increase in Ki(GMP) by a factor of 18. Km(MgATP)
      and Ki(MgATP) were very similar to those of the wild-type (WT) GK. The
      conformational stability of the mutant was lower than that of the WT by 1.0
      kcal/mol as measured by guanidine hydrochloride-induced denaturation. Detailed
      comparison of the TOCSY and NOESY spectra of the WT GK and the mutant indicated
      that the conformation of Y78F is little perturbed relative to that of the WT GK
      at the free state and the conformation of Y78F.GMP complex is also very similar
      to that of the WT.GMP complex. The results taken together showed that the
      hydrogen bond between Tyr-78 and GMP stabilizes the GK.GMP complex by 1.7
      kcal/mol, the ternary complex by 1.8 kcal/mol, and the transition state by 4.6
      kcal/mol. Tyr-78 is not essential for proper folding of the enzyme but it may
      contribute to the conformational stability. Solvent-accessible aromatic residues
      were identified by using the paramagnetic probe 4-hydroxy-2, 2,6,6
      tetramethylpiperidine-1-oxyl. Comparison of the free and GMP-bound forms of the
      WT GK by NMR indicated that there are changes in conformation and dynamics upon
      binding of GMP.

PMID- 9235933
TI  - Coordinate regulation of lipogenesis, the assembly and secretion of
      apolipoprotein B-containing lipoproteins by sterol response element binding
      protein 1.
AB  - Stable plasmid-driven expression of the liver-specific gene product cholesterol
      7alpha-hydroxylase (7alpha-hydroxylase) was used to alter the cellular content of
      transcriptionally active sterol response element binding protein 1 (SREBP1). As a
      result of stable expression of 7alpha-hydroxylase, individual single cell clones
      expressed varying amounts of mature SREBP1 protein. These single cell clones
      provided an opportunity to identify SREBP1-regulated genes that may influence the
      assembly and secretion of apoB-containing lipoproteins. Our results show that in
      McArdle rat hepatoma cells, which normally do not express 7alpha-hydroxylase,
      plasmid-driven expression of 7alpha-hydroxylase results in the following: 1) a
      linear relationship between (i) the cellular content of mature SREBP1 and 7alpha
      hydroxylase protein, (ii) the relative expression of 7alpha-hydroxylase mRNA and
      the mRNA's encoding the enzymes regulating fatty acid, i.e. acetyl-CoA
      carboxylase and sterol synthesis, i.e. HMG-CoA reductase, (iii) the relative
      expression of 7alpha-hydroxylase mRNA and microsomal triglyceride transfer
      protein mRNA, a gene product that is essential for the assembly and secretion of
      apoB-containing lipoproteins; 2) increased synthesis of all lipoprotein lipids
      (cholesterol, cholesterol esters, triglycerides, and phospholipids); and 3)
      increased secretion of apoB100 without any change in apoB mRNA. Cells expressing
      7alpha-hydroxylase contained significantly less cholesterol (both free and
      esterified). The increased cellular content of mature SREBP1 and increased
      secretion of apoB100 were concomitantly reversed by 25-hydroxycholesterol,
      suggesting that the content of mature SREBP1, known to be decreased by 25
      hydroxycholesterol, mediates the changes in the lipoprotein assembly and
      secretion pathway that are caused by 7alpha-hydroxylase. These data suggest that
      several steps in the assembly and secretion of apoB-containing lipoproteins by
      McArdle hepatoma cells may be coordinately linked through the cellular content of
      mature SREBP1.

PMID- 9235934
TI  - Identification of a firefly luciferase active site peptide using a benzophenone
      based photooxidation reagent.
AB  - Firefly luciferase catalyzes the highly efficient emission of yellow-green light
      from substrate luciferin by a series of reactions that require MgATP and
      molecular oxygen. We prepared 2-(4-benzoylphenyl)thiazole-4-carboxylic acid
      (BPTC), a novel benzophenone-based substrate analog, intending to use it in
      photoaffinity labeling studies to probe the luciferase active site. Instead, we
      found that while BPTC was a potent photoinactivating reagent for firefly
      luciferase, it was not a photoaffinity labeling agent. Using proteolysis, reverse
      phase high-performance liquid chromatography, tandem high performance liquid
      chromatography-electrospray ionization mass spectrometry, and Edman sequencing,
      we identified a single luciferase peptide, 244HHGF247, the degradation of which
      was directly correlated to luciferase photoinactivation. Results of enzyme
      kinetics and related studies were consistent with this peptide being at or near
      the luciferin binding site. Further, peptide model studies and additional
      investigations on the nature of the photoinactivation process strongly suggested
      that BPTC catalyzed the formation of singlet oxygen at the active site of the
      enzyme. We describe here an uncommon example of active site-directed
      photooxidation of an enzyme by singlet oxygen.

PMID- 9235935
TI  - Extensive glycosphingolipid depletion in the liver and lymphoid organs of mice
      treated with N-butyldeoxynojirimycin.
AB  - The imino sugar N-butyldeoxynojirimycin is an inhibitor of the ceramide-specific
      glucosyltransferase that catalyzes the first step in glycosphingolipid
      biosynthesis. It results in extensive glycosphingolipid depletion in cells
      treated in vitro, without causing toxicity. However, we currently do not know the
      degree to which glycosphingolipids can be depleted in vivo in a mammalian
      species. We have therefore administered N-butyldeoxynojirimycin long term to
      young mice and have found that glycosphingolipid levels are reduced (50-70%) in
      all tissues examined, without resulting in any overt pathology. When the lymphoid
      tissues from these mice were examined, they were found to be 50% acellular
      relative to non-lymphoid tissues. These data implicate a role for
      glycosphingolipids in the biology of the immune system or indicate an additional
      as yet unknown activity of N-butyldeoxynojirimycin. Extensive glycosphingolipid
      depletion resulting from N-butyldeoxynojirimycin administration is therefore well
      tolerated in adult mice, and this compound may be in an invaluable tool for
      probing glycosphingolipid functions in vivo. In addition, this drug may be
      effective in clinical situations where glycosphingolipid depletion would be
      desirable, such as the in the treatment of the human glycosphingolipidoses.

PMID- 9235937
TI  - Evidence that intramolecular interactions are involved in masking the activation
      domain of transcriptional activator Leu3p.
AB  - The Leu3 protein of Saccharomyces cerevisiae regulates the expression of genes
      involved in branched chain amino acid biosynthesis and in ammonia assimilation.
      It is modulated by alpha-isopropylmalate, an intermediate in leucine
      biosynthesis. In the presence of alpha-isopropylmalate, Leu3p is a
      transcriptional activator. In the absence of the signal molecule, the activation
      domain is masked, and Leu3p acts as a repressor. The recent discovery that Leu3p
      retains its regulatory properties when expressed in mammalian cells (Guo, H., and
      Kohlhaw, G. B. (1996) FEBS Lett. 390, 191-195) suggests that masking and
      unmasking of the activation domain occur without the participation of auxiliary
      proteins. Here we present experimental support for this notion and address the
      mechanism of masking. We show that modulation of Leu3p is exceedingly sensitive
      to mutations in the activation domain. An activation domain double mutant
      (D872N/D874N; designated Leu3-dd) was constructed that has the characteristics of
      a permanently masked activator. Using separately expressed segments containing
      either the DNA binding domain-middle region or the activation domain of wild type
      Leu3p (or Leu3-dd) in a modified yeast two-hybrid system, we provide direct
      evidence for alpha-isopropylmalate-dependent interaction between these segments.
      Finally, we use the phenotype of Leu3-dd-containing cells (slow growth in the
      absence of added leucine) to select for suppressor mutations that map to the
      middle region of Leu3-dd. The properties of nine such suppressors further support
      the idea that masking is an intramolecular process and suggest a means for
      mapping the surface involved in masking.

PMID- 9235936
TI  - Electron paramagnetic resonance studies of succinate:ubiquinone oxidoreductase
      from Paracoccus denitrificans. Evidence for a magnetic interaction between the
      3Fe-4S cluster and cytochrome b.
AB  - Electron paramagnetic resonance (EPR) studies of succinate:ubiquinone
      oxidoreductase (SQR) from Paracoccus denitrificans have been undertaken in the
      purified and membrane-bound states. Spectroscopic "signatures" accounting for the
      three iron-sulfur clusters (2Fe-2S, 3Fe-4S, and 4Fe-4S), cytochrome b, flavin,
      and protein-bound ubisemiquinone radicals have been obtained in air-oxidized,
      succinate-reduced, and dithionite-reduced preparations at 4-10 K. Spectra
      obtained at 170 K in the presence of excess succinate showed a signal typical of
      that of a flavin radical, but superimposed with another signal. The superimposed
      signal originated from two bound ubisemiquinones, as shown by spectral
      simulations. Power saturation measurements performed on the air-oxidized enzyme
      provided evidence for a weak magnetic dipolar interaction operating between the
      oxidized 3Fe-4S cluster and the oxidized cytochrome b. Power saturation
      experiments performed on the succinate- and dithionite-reduced forms of the
      enzyme demonstrated that the 4Fe-4S cluster is coupled weakly to both the 2Fe-2S
      and the 3Fe-4S clusters. Quantitative interpretation of these power saturation
      experiments has been achieved through redox calculations. They revealed that a
      spin-spin interaction between the reduced 3Fe-4S cluster and the cytochrome b
      (oxidized) may also exist. These findings form the first direct EPR evidence for
      a close proximity (</=2 nm) of the high potential 3Fe-4S cluster, situated in the
      succinate dehydrogenase part of the enzyme, and the low potential, low spin b
      heme in the membrane anchor of the enzyme.

PMID- 9235938
TI  - Identification of the antithrombin III heparin binding site.
AB  - The heparin binding site of the anticoagulant protein antithrombin III (ATIII)
      has been defined at high resolution by alanine scanning mutagenesis of 17 basic
      residues previously thought to interact with the cofactor based on chemical
      modification experiments, analysis of naturally occurring dysfunctional
      antithrombins, and proximity to helix D. The baculovirus expression system
      employed for this study produces antithrombin which is highly similar to plasma
      ATIII in its inhibition of thrombin and factor Xa and which resembles the
      naturally occurring beta-ATIII isoform in its interactions with high affinity
      heparin and pentasaccharide (Ersdal-Badju, E., Lu, A., Peng, X., Picard, V.,
      Zendehrouh, P., Turk, B., Bjork, I., Olson, S. T., and Bock, S. C. (1995)
      Biochem. J. 310, 323-330). Relative heparin affinities of basic-to-Ala
      substitution mutants were determined by NaCl gradient elution from heparin
      columns. The data show that only a subset of the previously implicated basic
      residues are critical for binding to heparin. The key heparin binding residues,
      Lys-11, Arg-13, Arg-24, Arg-47, Lys-125, Arg-129, and Arg-145, line a 50-A long
      channel on the surface of ATIII. Comparisons of binding residue positions in the
      structure of P14-inserted ATIII and models of native antithrombin, derived from
      the structures of native ovalbumin and native antichymotrypsin, suggest that
      heparin may activate antithrombin by breaking salt bridges that stabilize its
      native conformation. Specifically, heparin release of intramolecular helix D
      sheet B salt bridges may facilitate s123AhDEF movement and generation of an
      activated species that is conformationally primed for reactive loop uptake by
      central beta-sheet A and for inhibitory complex formation. In addition to
      providing a structural explanation for the conformational change observed upon
      heparin binding to antithrombin III, differences in the affinities of native,
      heparin-bound, complexed, and cleaved ATIII molecules for heparin can be
      explained based on the identified binding site and suggest why heparin functions
      catalytically and is released from antithrombin upon inhibitory complex
      formation.

PMID- 9235939
TI  - Identification and subcellular localization of the subunits of L-type calcium
      channels and adenylyl cyclase in cardiac myocytes.
AB  - The properties of cardiac L-type channels have been well characterized
      electrophysiologically, and many such studies have demonstrated that the channels
      are regulated by a cAMP-dependent pathway. However, the subunit composition of
      native cardiac L-type calcium channels has not been completely defined.
      Furthermore, a very important question exists regarding the status of the C
      terminal domain of the pore-forming alpha1 subunit, as this domain has the
      potential to be the target of protein kinases but may be truncated as a result of
      post-translational processing. In the present studies, the alpha1C and beta2
      subunits were identified by subunit-specific antibodies after partial
      purification from heart membranes, or immunoprecipitation from cardiac myocytes.
      Both the beta2 and the full-length alpha1C subunits were found to be expressed
      and co-localized in intact cardiac myocytes along T-tubule membranes. Using a
      quantitative antibody binding analysis, we demonstrated that the majority of the
      alpha1C subunits in intact cardiac myocytes appear to be full-length. In
      addition, we observed that adenylyl cyclase is localized in a pattern similar to
      the channel subunits in cardiac myocytes. Taken together, our results provide new
      insights into the structural basis for understanding the regulation of L-type
      calcium channels by a cAMP-mediated signaling pathway.

PMID- 9235940
TI  - The phosphorylation of bovine DNase I Asn-linked oligosaccharides is dependent on
      specific lysine and arginine residues.
AB  - The secretory glycoprotein DNase I acquires mannose 6-phosphate moieties on its
      Asn-linked oligosaccharides, indicating that it is a substrate for UDP
      GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase
      (phosphotransferase) (Cacia, J., Quan, C., and Frenz, J. (1995) Glycobiology 4,
      99). Phosphotransferase recognizes a conformation-dependent protein determinant
      that is present in lysosomal hydrolases, but absent in most secretory
      glycoproteins. To identify the amino acid residues of DNase I that are required
      for interaction with phosphotransferase, wild-type and mutant forms of bovine
      DNase I were expressed in COS-1 cells and the extent of oligosaccharide
      phosphorylation determined. Phosphorylation of DNase I oligosaccharides decreased
      from 12.6% to 2.3% when Lys-50, Lys-124, and Arg-27 were mutated to alanines,
      indicating that these residues are required for the basal level of
      phosphorylation. Mutation of lysines at other positions did not impair
      phosphorylation, demonstrating the selectivity of this process. When Arg-27 was
      replaced with a lysine, phosphorylation increased to 54%, showing that
      phosphotransferase prefers lysine residues to arginines. Mutation of Asn-74 to a
      lysine also increased phosphorylation to 50.3%, and the double mutant (R27K/N74K)
      was phosphorylated 79%, equivalent to the values obtained with lysosomal
      hydrolases. Interestingly, Lys-27 and Lys-74 caused selective phosphorylation of
      the neighboring Asn-linked oligosaccharide. Finally, mutation of Lys-117 to an
      alanine stimulated phosphorylation, demonstrating that some residues may be
      negative regulators of this process. We conclude that selected lysine and
      arginine residues on the surface of DNase I constitute the major elements of the
      phosphotransferase recognition domain present on this secretory glycoprotein.

PMID- 9235941
TI  - A novel link between REC2, a DNA recombinase, the retinoblastoma protein, and
      apoptosis.
AB  - The REC2 recombinase is essential for recombinational repair following DNA damage
      as well as for successful meiosis and gene targeting in the corn smut Ustilago
      maydis. Here we report that overexpression of REC2 induced apoptotic cell death
      in human HuH-7, Hep G2, and Hep 3B hepatoma cells. Apoptosis was related to
      recombinase activity and was significantly increased by inhibition of
      retinoblastoma (Rb) expression with transforming growth factor-beta1. REC2
      induced apoptosis was associated with a significantly reduced percentage of cells
      in the G1 phase of the cell cycle and a significant reduction in G2/M only in the
      Rb(-/-) Hep 3B cells. Overexpression of REC2 resulted in increased abundance of
      the hyperphosphorylated form of Rb. However, by immunoprecipitation REC2 was
      associated primarily with hypophosphorylated Rb, suggesting that REC2 may be
      involved in modulating the phosphorylation state of Rb. The A and B pocket
      domains with the spacer amino acid sequence and the carboxyl-terminal region of
      Rb were required for maximal binding to REC2. Overexpression of Rb significantly
      inhibited REC2-induced apoptosis even in the presence of transforming growth
      factor-beta1. Taken together, these data suggest a novel interaction of Rb with
      the recombinase REC2 and a role for this complex in bridging DNA recombination
      and apoptosis.

PMID- 9235942
TI  - Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin
      related motor HsEg5 to the dynactin subunit p150.
AB  - The kinesin-related motor HsEg5 is essential for centrosome separation, and its
      association with centrosomes appears to be regulated by phosphorylation of tail
      residue threonine 927 by the p34(cdc2) protein kinase. To identify proteins able
      to interact with the tail of HsEg5, we performed a yeast two-hybrid screen with a
      HsEg5 stalk-tail construct as bait. We isolated a cDNA coding for the central,
      alpha-helical region of human p150(Glued), a prominent component of the dynactin
      complex. The interaction between HsEg5 and p150(Glued) was enhanced upon
      activation of p34(CDC28), the budding yeast homolog of p34(cdc2), provided that
      HsEg5 had a phosphorylatable residue at position 927. Phosphorylation also
      enhanced the specific binding of p150(Glued) to the tail domain of HsEg5 in
      vitro, indicating that the two proteins are able to interact directly.
      Immunofluorescence microscopy revealed co-localization of HsEg5 and p150(Glued)
      during mitosis but not during interphase, consistent with a cell cycle-dependent
      association between the two proteins. Taken together, these results suggest that
      HsEg5 and p150(Glued) may interact in mammalian cells in vivo and that p34(cdc2)
      may regulate this interaction. Furthermore, they imply that the dynactin complex
      may functionally interact not only with dynein but also with kinesin-related
      motors.

PMID- 9235943
TI  - Apotransferrin and holotransferrin undergo different endocytic cycles in
      intestinal epithelia (Caco-2) cells.
AB  - Previous studies have demonstrated that diferric transferrin and apotransferrin
      compete for the binding to basolateral transferrin receptors and that transferrin
      mediated iron uptake by Caco-2 cells is inhibited by apotransferrin to a larger
      extent than that predicted solely by receptor competition. This inhibition can
      have important implications in determining the net exchange of iron between
      intestinal cells and the basolateral milieu. Accordingly, we further
      characterized the endocytic cycles of apotransferrin and diferric transferrin in
      Caco-2 cells. We found that after internalization both apotransferrin and
      diferric transferrin recycled to the cell exterior, but that apotransferrin had a
      protracted endocytic cycle. Confocal microscopy studies revealed a different
      cellular distribution of apotransferrin and diferric transferrin; both were found
      in a compartment close to the basal membrane, but apotransferrin reached as well
      regions closer to the apical membrane. Moreover, the intracellular distribution
      of transferrin receptors was influenced by the iron load of transferrin; cells
      incubated with apotransferrin presented a more apical distribution of transferrin
      receptors than cells incubated with diferric transferrin. These results indicate
      for the first time that the endocytic cycle of transferrin receptors in
      intestinal epithelial cells is determined by the iron content of transferrin.
      They explain also the marked inhibitory effect of apotransferrin on transferrin
      mediated iron uptake by Caco-2 cells, since incubation of cells with
      apotransferrin resulted in the actual sequestration of the receptor in the cell
      interior.

PMID- 9235944
TI  - Alpha4 integrin binding interfaces on VCAM-1 and MAdCAM-1. Integrin binding
      footprints identify accessory binding sites that play a role in integrin
      specificity.
AB  - Integrins are a family of heterodimeric adhesion receptors that mediate cellular
      interactions with a range of matrix components and cell surface proteins.
      Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial cell ligand for two
      leukocyte integrins (alpha4beta1 and alpha4beta7). A related CAM, mucosal
      addressin cell adhesion molecule-1 (MAdCAM-1) is recognized by alpha4beta7 but is
      a poor ligand for alpha4beta1. Previous studies have revealed that all alpha4
      integrin-ligand interactions are dependent on a key acidic ligand motif centered
      on the CAM domain 1 C-D loop region. By generating VCAM-1/MAdCAM-1 chimeras and
      testing recombinant proteins in cell adhesion assays we have found that
      alpha4beta1 binds to the MAdCAM-1 adhesion motif when present in VCAM-1, but not
      when the VCAM-1 motif was present in MAdCAM-1, suggesting that this region does
      not contain all of the information necessary to determine integrin binding
      specificity. To characterize integrin-CAM specificity further we measured
      alpha4beta1 and alpha4beta7 binding to a comprehensive set of mutant VCAM-1
      constructs containing amino acid substitutions within the predicted integrin
      adhesion face. These data revealed the presence of key "regulatory residues"
      adjacent to integrin contact sites and an important difference in the "footprint"
      of alpha4beta1 and alpha4beta7 that was associated with an accessory binding site
      located in VCAM-1 Ig domain 2. The analogous region in MAdCAM-1 is markedly
      different in size and sequence and when mutated abolishes integrin binding
      activity.

PMID- 9235946
TI  - The lymphotoxin-alpha (LTalpha) subunit is essential for the assembly, but not
      for the receptor specificity, of the membrane-anchored LTalpha1beta2
      heterotrimeric ligand.
AB  - The lymphotoxins (LT) alpha and beta, members of the tumor necrosis factor (TNF)
      cytokine superfamily, are implicated as important regulators and developmental
      factors for the immune system. LTalpha is secreted as a homotrimer and signals
      through two TNF receptors of 55-60 kDa (TNFR60) or 75-80 kDa (TNFR80). LTalpha
      also assembles with LTbeta into a membrane-anchored, heterotrimeric LTalpha1beta2
      complex that engages a distinct cognate receptor, the LTbeta receptor (LTbetaR).
      To investigate the role of the LTalpha subunit in the function of the membrane
      LTalpha1beta2 complex, gene transfer via baculovirus was used to assemble LTalpha
      and -beta complexes in insect cells. LTalpha containing mutations at D50N or
      Y108F are secreted as homotrimers that fail to bind either TNF receptor and are
      functionally inactive in triggering cell death of the HT29 adenocarcinoma cell
      line. In contrast, these mutant LTalpha proteins retain the ability to co
      assemble with LTbeta into membrane-anchored LTalpha1beta2 complexes that engage
      the LTbetaR and trigger the death of HT29 cells. Membrane-anchored LTbeta
      expressed on the cell surface in absence of the LTalpha subunit binds the LTbetaR
      but is functionally inactive in the cell death assay. These results indicate that
      the TNF receptor-binding regions of the LTalpha subunit are not necessary for
      engagement of the LTbetaR, but the LTalpha subunit is required for the assembly
      of LTbeta into a functional heteromeric ligand.

PMID- 9235945
TI  - Transduction of activation signal that follows HIV-1 binding to CD4 and CD4
      dimerization involves the immunoglobulin CDR3-like region in domain 1 of CD4.
AB  - The role of CD4 during the human immunodeficiency virus type 1 (HIV-1) life cycle
      in T cells is not restricted to binding functions. HIV-1 binding to CD4 also
      triggers signals that lead to nuclear translocation of NF-kappaB and are
      important to the productive infection process. In addition to its cytoplasmic
      tail, in the ectodomain, the immunoglobulin (Ig) CDR3-like region of CD4 domain 1
      seemed to play a role in this cascade of signals. We demonstrate in this work
      that the structural integrity of the CDR3-like loop is required for signal
      transduction. Substitutions of negatively charged residues by positively charged
      residues within the CDR3-like loop either inhibited NF-kappaB translocation after
      HIV-1 and gp120-anti-gp120 immune complexes binding to E91K,E92K mutants or
      induced its constitutive activation for E87K,D88K mutants. Moreover, A2.01-3B
      cells expressing the E91K,E92K mutant exhibited a lower HIV-1Lai replication.
      These cells, however, expressed p56(lck), demonstrated NF-kappaB translocation
      upon PMA stimulation, bound HIV-1Lai envelope glycoprotein with high affinity,
      and contained HIV-1 DNA 24 h after exposure to virus. E91K, E92K, and E87K,D88K
      mutant CD4 molecules were unable to bind a CD4 synthetic aromatically modified
      exocyclic, CDR3.AME-(82-89), that mimics the CDR3-like loop structure and binds
      to native cell surface CD4. This result together with molecular modeling studies
      indicates that the CDR3.AME-(82-89) analog binds to the CDR3-like loop of CD4 and
      strongly suggests that this region represents a site for CD4 dimerization. The
      negative charges on the CDR3-like loop thus appear critical for CD4-mediated
      signal transduction most likely related to CD4 dimer formation.

PMID- 9235947
TI  - Molecular cloning of a new interferon-induced PML nuclear body-associated
      protein.
AB  - Transcriptional induction of genes is an essential part of the cellular response
      to interferons. We have established a cDNA library from human lymphoblastoid
      Daudi cells treated for 16 h with human alpha/beta-interferon (IFN) and made use
      of differential screening to search for as yet unidentified IFN-regulated genes.
      In the course of this study, we have isolated a human cDNA that codes for a 20
      kDa protein sharing striking homology with the product of the Xenopus laevis
      XPMC2 gene. This new gene is induced by both type I and II IFNs in various cell
      lines and will be referred to as ISG20 for interferon-stimulated gene product of
      20 kDa. Confocal immunofluorescence analysis of the subcellular localization of
      ISG20 protein reveals that it is closely associated with PML and SP100 gene
      products within the large nuclear matrix-associated multiprotein complexes termed
      the PML nuclear bodies.

PMID- 9235948
TI  - Role of the C terminus in histamine H2 receptor signaling, desensitization, and
      agonist-induced internalization.
AB  - To evaluate the role of the histamine H2 receptor C terminus in signaling,
      desensitization, and agonist-induced internalization, canine H2 receptors with
      truncated C termini were generated. Wild-type (WT) and truncated receptors were
      tagged at their N termini with a hemagglutinin (HA) epitope and expressed in COS7
      cells. Most of the C-terminal intracellular tail could be truncated (51 of 70
      residues, termed T308 mutant) without loss of functions: cAMP production,
      tiotidine binding, and plasma membrane targeting. In fact, the T308 mutant
      produced more cAMP than the WT when cell-surface expression per cell was
      equivalent. Pretreatment of cells with 10(-5) M histamine desensitized cAMP
      productions via WT and T308 receptors to similar extents. Incubation of cells
      expressing WT receptors with 10(-5) M histamine reduced cell-surface anti-HA
      antibody binding by approximately 30% (by 30 min, t1/2 approximately 15 min), but
      did not affect the Bmax of tiotidine in membrane fractions, which represents
      total receptor amounts, suggesting that WT receptors were internalized from the
      cell surface. In contrast, no internalization was observed with T308 receptors
      following histamine treatment. A mutant with a deletion of the 30 C-terminal
      amino acids, termed T329, was functional but was as potent as the WT in terms of
      cAMP production. Apart from being desensitized by histamine, the internalization
      of the receptor was indistinguishable from that of the WT. Internalization was
      observed in the T320 but not in T313 mutant, narrowing the region involved in
      internalization to that between Glu314 and Asn320 (ETSLRSN). Of these seven
      residues, either Thr315, Ser316, or both, were replaced with Ala. Thr315 and
      Ser316 are conserved among species. The mutation at Thr315 (but not that at
      Ser316) abolished internalization. Taken together, these results demonstrate that
      Thr315 is involved in agonist-induced internalization. Furthermore, the finding
      that T308 receptors were desensitized in the absence of internalization suggests
      that internalization and desensitization are meditated by independent mechanisms.

PMID- 9235949
TI  - HSP70 binding sites in the tumor suppressor protein p53.
AB  - Mutations within conserved regions of the tumor suppressor protein, p53, result
      in oncogenic forms of the protein with altered tertiary structures. In most
      cases, the mutant p53 proteins are selectively recognized and bound by members of
      the HSP70 family of molecular chaperones, but the binding site(s) in p53 for
      these chaperones have not been clearly defined. We have screened a library of
      overlapping biotinylated peptides, spanning the entire human p53 sequence, for
      binding to the HSP70 proteins, Hsc70 and DnaK. We show that most of the high
      affinity binding sites for these proteins map to secondary structure elements,
      particularly beta-strands, in the hydrophobic core of the central DNA binding
      domain, where the majority of oncogenic p53 mutations are found. Although
      peptides corresponding to the C-terminal region of p53 also contain potential
      binding sites, p53 proteins with C-terminal deletions are capable of binding to
      Hsc70, indicating that this region is not required for complex formation. We
      propose that mutations in the p53 protein alter the tertiary structure of the
      central DNA binding domain, thus exposing high affinity HSP70 binding sites that
      are cryptic in the wild-type molecule.

PMID- 9235950
TI  - Analysis of cationic liposome-mediated interactions of plasmid DNA with murine
      and human melanoma cells in vitro.
AB  - Lipid-based DNA transfer formulations are typically selected on the basis of in
      vitro transfection studies where the activity of specific formulations is defined
      by transgene expression. It is unclear, however, whether expression is directly
      related to the efficiency of DNA transfer. In an attempt to correlate DNA
      transfer with transgene expression, we used a simple assay consisting of
      measuring DNA (3H-plasmid encoding for beta-galactosidase) binding to murine
      (B16/BL6) and human (KZ) melanoma cells in vitro at 4 and 37 degrees C. The
      difference in cell association at these temperatures was assumed to be a
      consequence of DNA uptake, an assumption that was confirmed by protease removal
      of cell surface-associated DNA. DNA associated with B16/BL6 melanoma cells (up to
      30 ng or 12% of the added DNA) following incubation with dioleoyldimethylammonium
      chloride/dioleoylphosphatidylethanolamine (DOPE) liposome-DNA aggregates was
      comparable to that achieved with 1,2-dioleoyloxypropyl-3-trimethylammonium
      bromide/DOPE or dimethyldioctadecylammonium bromide/DOPE liposomes; however,
      transgene expression was 2- and 5-fold less for the latter two formulations,
      respectively. Similarly, equivalent amounts of DNA delivery were achieved with
      B16/BL6 and KZ melanoma cells, yet the level of transgene expression in the KZ
      cells was undetectable. It was demonstrated that the lack of transgene expression
      was not a consequence of cell-specific differences in DNA degradation.

PMID- 9235951
TI  - Genetic analysis of purine metabolism in Leishmania donovani.
AB  - To dissect the contributions of hypoxanthine-guanine phosphoribosyltransferase
      (HGPRT), adenine phosphoribosyltransferase (APRT), and adenosine kinase (AK) to
      purine salvage in Leishmania donovani, null mutants genetically deficient in
      HGPRT and/or APRT were generated by targeted gene replacement in wild type cells
      and preexisting mutant strains lacking either APRT or AK activity. These
      knockouts were obtained either by double targeted gene replacement or by single
      gene replacement followed by negative selection for loss-of-heterozygosity.
      Genotypes were confirmed by Southern blotting and the resultant phenotypes
      evaluated by enzymatic assay, resistance to cytotoxic drugs, ability to
      incorporate radiolabeled purine bases, and growth on various purine sources. All
      mutant strains could propagate in defined growth medium containing any single
      purine source and could metabolize exogenous [3H]hypoxanthine to the nucleotide
      level. The surprising ability of mutant L. donovani lacking HGPRT, APRT, and/or
      AK to incorporate and grow in hypoxanthine could be attributed to the ability of
      the parasite xanthine phosphoribosyltransferase enzyme to salvage hypoxanthine.
      These genetic studies indicate that HGPRT, APRT, and AK, individually or in any
      combination, are not essential for the survival and growth of the promastigote
      stage of L. donovani and intimate an important, if not crucial, role for xanthine
      phosphoribosyltransferase in purine salvage.

PMID- 9235952
TI  - Two-dimensional crystals of photosystem I in higher plant grana margins.
AB  - In this report, we present new structural data on the size, shape, and oligomeric
      form of higher plant photosystem I (PSI) formed within the thylakoid grana
      margins. We show that PSI complexes can be assembled into ordered molecular
      monolayers (two-dimensional crystals) using thylakoid membranes from a variety of
      higher plant sources. Digital image analysis of negatively stained two
      dimensional crystals (a = 26.9 nm, b = 28.0 nm, gamma = 90 degrees, p22121 plane
      group) resulted in a projection map consisting of 4 monomers/unit cell. Higher
      plant PSI is slightly larger than its cyanobacterial equivalent but shows many
      similar features. Structural changes after urea and salt washing of the crystals
      supported the biochemical characterization and were mainly assigned to the
      stromal side of the complex where the psaC, psaD, and psaE gene products are
      known to be bound. Labeling with ferredoxin-colloidal gold complexes provided
      direct evidence for a segregated PSI population, with 5 nm diameter ferredoxin
      gold particles enriched in the thylakoid grana margins and the two-dimensional
      crystals. This lateral segregation of photosynthetic complexes is important for
      the understanding of the kinetics of electron transfer between photosystem II and
      PSI in higher plants.

PMID- 9235953
TI  - Functional analysis of glycosyltransferases encoded by the capsular
      polysaccharide biosynthesis locus of Streptococcus pneumoniae serotype 14.
AB  - Bacteria belonging to the species Streptococcus pneumoniae vary in their capsule.
      Presently, 90 capsular serotypes are known, all possessing their own specific
      polysaccharide structure. Little is known about the biosynthesis of these
      capsular polysaccharides. The cps locus of S. pneumoniae serotype 14 was cloned.
      So far, 7 open reading frames have been sequenced, cps14B to cps14H. The gene
      products are similar to proteins involved in bacterial polysaccharide
      biosynthesis, both of Gram-negative and -positive micro-organisms. Gene-specific
      mutants were created for cps14D to cps14H by insertional mutagenesis. All mutants
      no longer agglutinated with a monoclonal antibody against type 14 capsule
      polysaccharides. The biosynthetic function of cps14E and cps14G was determined by
      analysis of the intermediates in the synthesis of the oligosaccharide subunit,
      formed in membrane preparations of the wild-type and mutant strains and in
      membrane preparations of Escherichia coli expressing the pneumococcal
      glycosyltransferases. The enzyme encoded by cps14E is a glucosyl-1-phosphate
      transferase that links glucose to a lipid carrier, the first step in the
      biosynthesis of the type 14 repeating unit. The gene product of cps14G encodes a
      beta-1,4-galactosyltransferase, the enzyme responsible for the second step in the
      subunit synthesis, the transfer of galactose to lipid-linked glucose.

PMID- 9235954
TI  - p38-2, a novel mitogen-activated protein kinase with distinct properties.
AB  - Mitogen-activated protein (MAP) kinases are involved in many cellular processes.
      Here we describe the cloning and characterization of a new MAP kinase, p38-2. p38
      2 belongs to the p38 subfamily of MAP kinases and shares with it the TGY
      phosphorylation motif. The complete p38-2 cDNA was isolated by polymerase chain
      reaction. It encodes a 364-amino acid protein with 73% identity to p38. Two
      shorter isoforms missing the phosphorylation motif were identified. Analysis of
      various tissues demonstrated that p38-2 is differently expressed from p38.
      Highest expression levels were found in heart and skeletal muscle. Like p38, p38
      2 is activated by stress-inducing signals and proinflammatory cytokines. The
      preferred upstream kinase is MEK6. Although p38-2 and p38 phosphorylate the same
      substrates, the site specificity of phosphorylation can differ as shown by two
      dimensional phosphopeptide analysis of Sap-1a. Additionally, kinetic studies
      showed that p38-2 appears to be about 180 times more active than p38 on certain
      substrates such as ATF2. Both kinases are inhibited by a class of pyridinyl
      imidazoles. p38-2 phosphorylation of ATF2 and Sap-1a but not Elk1 results in
      increased transcriptional activity of these factors. A sequential kinetic
      mechanism of p38-2 is suggested by steady state kinetic analysis. In conclusion,
      p38-2 may be an important component of the stress response required for the
      homeostasis of a cell.

PMID- 9235955
TI  - Molecular cloning of a novel human CC chemokine secondary lymphoid-tissue
      chemokine that is a potent chemoattractant for lymphocytes and mapped to
      chromosome 9p13.
AB  - By searching the Expressed Sequence Tag (EST) data base, we identified partial
      cDNA sequences potentially encoding a novel human CC chemokine. We determined the
      entire cDNA sequence which encodes a highly basic polypeptide of 134 amino acids
      total with a putative signal peptide of 23 amino acids. The predicted mature
      protein of 111 amino acids has the four canonical cysteine residues and shows 21
      33% identity to other human CC chemokines, but has a unique carboxyl-terminal
      extension of about 30 amino acids which contains two extra cysteine residues. The
      mRNA was expressed strongly in tissues such as the lymph nodes, Appendix, and
      spleen. The recombinant protein, which was produced by the baculovirus system and
      purified to homogeneity, was a highly efficient chemoattractant for certain human
      T cell lines and a highly potent one for freshly isolated peripheral blood
      lymphocytes and cultured normal T cells expanded by phytohemagglutinin and
      interleukin 2. Unlike most other CC chemokines, however, this novel chemokine was
      not chemotactic for monocytes or neutrophils, suggesting that it is specific for
      lymphocytes. From these results, we designated this novel CC chemokine as SLC
      from secondary lymphoid-tissue chemokine. SLC fused with the secreted form of
      alkaline phosphatase (SLC-SEAP) was used to characterize the SLC receptor.
      Binding of SLC-SEAP to freshly isolated lymphocytes was blocked by SLC (IC50,
      0.12 nM) but not by any other CC chemokine so far tested, suggesting that resting
      lymphocytes express a class of receptors highly specific for SLC. By using
      somatic cell hybrids, radiation hybrids, and selected yeast and bacterial
      artificial chromosome clones, we mapped the SLC gene (SCYA21) at chromosome 9p13
      and between chromosomal markers, D9S1978(WI-8765) and AFM326vd1, where the gene
      for another novel CC chemokine termed ELC from EBI1-ligand chemokine (SCYA19)
      also exists. Collectively, SLC is a novel CC chemokine specific for lymphocytes
      and, together with ELC, constitutes a new group of chemokines localized at
      chromosome 9p13.

PMID- 9235956
TI  - Insulin and interleukin-4 induce desensitization to the mitogenic effects of
      insulin-like growth factor-I. Pivotal role for insulin receptor substrate-2.
AB  - Insulin-induced desensitization to insulin-like growth factor-I (IGF-I)
      stimulated mitogenesis in bovine fibroblasts involves steps distal to IGF-I
      binding to its tyrosine kinase receptor. When quiescent cultures of bovine
      fibroblasts were stimulated with 10 nM IGF-I and total cell lysates immunoblotted
      with anti-phosphotyrosine antibody, we observed a band at approximately 97 kDa,
      representing the beta-subunit of the IGF-I receptor, and a predominant tyrosyl
      phosphorylated species migrating as a broad band between 170 and 190 kDa. The
      majority of proteins in this latter band were immunoprecipitated by antibodies
      against insulin receptor substrate (IRS)-2 and not by antibodies against IRS-1.
      Pretreatment of bovine fibroblasts with 10 nM insulin for 48 h blocked subsequent
      IGF-I-stimulated DNA synthesis and the IGF-I-induced increase in tyrosyl
      phosphorylated IRS-2. Insulin pretreatment did not alter IRS-1 or IRS-2
      expression by these cells, as assessed by metabolic labeling and direct
      immunoblotting with IRS antibodies. The interleukin-4 (IL-4) cytokine receptor
      also has IRS-2 as its major substrate for tyrosine phosphorylation. Although 10
      nM IL-4 was as effective as 10 nM IGF-I in stimulating IRS-2 phosphorylation, 10
      nM IL-4 did not have comparable mitogenic power in these cells. Nonetheless,
      pretreatment of bovine fibroblasts with IL-4 inhibited IGF-I-stimulated DNA
      synthesis by 50-60%, concomitant with a decrease in IGF-I-induced IRS-2
      phosphorylation. Insulin-induced desensitization could be prevented if a specific
      inhibitor of phosphatidylinositol 3-kinase (LY294002), but not an inhibitor of
      mitogen-activated protein kinase (PD98059), was present during the preincubation
      period. LY294002 also prevented the shift in IRS-2 molecular mass in response to
      prolonged incubation of cells with insulin. These data indicate that, in a
      nontransformed cell system, IRS-2 plays a key role in cellular desensitization to
      IGF-I-stimulated mitogenesis most likely through a feedback mechanism in the
      phosphatidylinositol 3-kinase pathway. Furthermore, they suggest that signaling
      through IRS-2 may provide an important point of integration for hormone, growth
      factor, and cytokine receptor systems that regulate critical cellular growth
      responses.

PMID- 9235957
TI  - Escherichia coli cytotoxic necrotizing factor 1 (CNF1), a toxin that activates
      the Rho GTPase.
AB  - Cytotoxic necrotizing factor 1 (CNF1), a 110-kDa protein toxin from pathogenic
      Escherichia coli induces actin reorganization into stress fibers and retraction
      fibers in human epithelial cultured cells allowing them to spread. CNF1 is acting
      in the cytosol since microinjection of the toxin into HEp-2 cells mimics the
      effects of the externally applied CNF1. Incubation in vitro of CNF1 with
      recombinant small GTPases induces a modification of Rho (but not of Rac, Cdc42,
      Ras, or Rab6) as demonstrated by a discrete increase in the apparent molecular
      weight of the molecule. Preincubation of cells with CNF1 impairs the cytotoxic
      effects of Clostridium difficile toxin B, which inactivates Rho but not those of
      Clostridium sordellii LT toxin, which inhibits Ras and Rac. As shown for Rho-GTP,
      CNF1 activates, in a time- and dose-dependent manner, a cytoskeleton-associated
      phosphatidylinositol 4-phosphate 5-kinase. However, neither the
      phosphatidylinositol 4,5-bisphosphate (PIP2) nor the phosphatidylinositol 3,4
      bisphosphate (PI 3,4-P2) or 3,4,5-trisphosphate (PIP3) cellular content were
      found increased in CNF1 treated HEp-2 cells. Cellular effects of CNF1 were not
      blocked by LY294002, a stable inhibitor of the phosphoinositide 3-kinase.
      Incubation of HEp-2 cells with CNF1 induces relocalization of myosin 2 in stress
      fibers but not in retraction fibers. Altogether, our data indicate that CNF1 is a
      toxin that selectively activates the Rho GTP-binding protein, thus inducing
      contractility and cell spreading.

PMID- 9235958
TI  - Disassembly of RanGTP-karyopherin beta complex, an intermediate in nuclear
      protein import.
AB  - We previously showed that RanGTP forms a 1:1 complex with karyopherin beta that
      renders RanGTP inaccessible to RanGAP (Floer, M., and Blobel, G. (1996) J. Biol.
      Chem. 271, 5313-5316) and karyopherin beta functionally inactive (Rexach, M., and
      Blobel, G. (1995) Cell 83, 683-692). Recycling of both factors for another round
      of function requires dissociation of the RanGTP-karyopherin beta complex. Here we
      show using BIAcoreTM, a solution binding assay, and GTP hydrolysis and exchange
      assays, with yeast proteins, that karyopherin beta and RanGTP are recycled
      efficiently in a reaction that involves karyopherin alpha, RanBP1, RanGAP, and
      the C terminus of the nucleoporin Nup1. We find that karyopherin alpha first
      releases RanGTP from karyopherin beta in a reaction that does not require GTP
      hydrolysis. The released RanGTP is then sequestered by RanBP1, and the newly
      formed karyopherin alphabeta binds to the C terminus of Nup1. Finally, RanGTP is
      converted to RanGDP via nucleotide hydrolysis when RanGAP is present. Conversion
      of RanGTP to RanGDP can also occur via nucleotide exchange in the presence of
      RanGEF, an excess of GDP, and if RanBP1 is absent. Additional nucleoporin domains
      that bind karyopherin alphabeta stimulate recycling of karyopherin beta and Ran
      in a manner similar to the C terminus of Nup1.

PMID- 9235959
TI  - Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured
      human neurons.
AB  - Hyperphosphorylated tau is the major component of paired helical filaments in
      neurofibrillary lesions associated with Alzheimer's disease. Hyperphosphorylation
      reduces the affinity of tau for microtubules and is thought to be a critical
      event in the pathogenesis of this disease. Recently, glycogen-synthase kinase-3
      has been shown to phosphorylate tau in vitro and in non-neuronal cells
      transfected with tau. The activity of glycogen-synthase kinase-3 can be down
      regulated in response to insulin or insulin-like growth factor-1 through the
      activation of the phosphatidylinositol 3-kinase pathway. We therefore hypothesize
      that insulin or insulin-like growth factor-1 may affect tau phosphorylation
      through the inhibition of glycogen-synthase kinase-3 in neurons. Using cultured
      human neuronal NT2N cells, we demonstrate that glycogen-synthase kinase-3
      phosphorylates tau and reduces its affinity for microtubules and that insulin and
      insulin-like growth factor-1 stimulation reduces tau phosphorylation and promotes
      tau binding to microtubules. We further demonstrate that these effects of insulin
      and insulin-like growth factor-1 are mediated through the inhibition of glycogen
      synthase kinase-3 via the phosphatidylinositol 3-kinase/protein kinase B
      signaling pathway.

PMID- 9235960
TI  - Retrograde transport of KDEL-bearing B-fragment of Shiga toxin.
AB  - To investigate retrograde transport along the biosynthetic/secretory pathway, we
      have constructed a recombinant Shiga toxin B-fragment carrying an N-glycosylation
      site and a KDEL retrieval motif at its carboxyl terminus (B-Glyc-KDEL). After
      incubation with HeLa cells, B-Glyc-KDEL was progressively glycosylated in the
      endoplasmic reticulum (ER) and remained stably associated with this compartment.
      B-fragment with a nonfunctional KDEL sequence (B-Glyc-KDELGL) was glycosylated
      with about the same kinetics as B-Glyc-KDEL but localized at steady state to the
      Golgi apparatus. Morphological studies showed that B-Glyc-KDEL was delivered from
      the plasma membrane, via endosomes and the cisternae of the Golgi apparatus, to
      the ER. Moreover, the addition of a sulfation site allowed us to show that B-Glyc
      KDEL on transit to the ER entered the Golgi apparatus through the trans-Golgi
      network. Transport of B-Glyc-KDEL to the ER was slowed down by nocodazole,
      indicating that microtubules are important for the retrograde pathway. Our
      results document the existence of a continuous pathway from the plasma membrane
      to the endoplasmic reticulum via the Golgi apparatus and show that a fully folded
      exogenous protein arriving in the endoplasmic reticulum via this pathway can
      undergo N-glycosylation.

PMID- 9235961
TI  - The large subunit of the DNA replication complex C (DSEB/RF-C140) cleaved and
      inactivated by caspase-3 (CPP32/YAMA) during Fas-induced apoptosis.
AB  - We report the identification of the large subunit of the DNA replication factor,
      DSEB/RF-C140, as a new substrate for caspase-3 (CPP32/YAMA), or a very closely
      related protease activated during Fas-induced apoptosis in Jurkat T cells.
      DSEB/RF-C140 is a multifunctional DNA-binding protein with sequence homology to
      poly(ADP-ribose) polymerase (PARP). This similarity includes a consensus DEVD/G
      cleavage site for caspase-3. Cleavage of DSEB/RF-C140 is predicted to occurs
      between Asp706 and Gly707, generating 87-kDa and 53-kDa fragments. An antiserum
      raised against the amino-terminal domain of DSEB/RF-C140 detects a new 87-kDa
      protein in Jurkat T cells in which apoptosis is activated by a monoclonal
      antibody to Fas. This cleavage occurs shortly after PARP cleavage. In vitro
      translated DSEB/RF-C140 is specifically cleaved into the predicted fragments when
      incubated with a cytoplasmic extract from Fas antibody-treated cells. Proteolytic
      cleavage was prevented by substituting Asp706 by an alanine in the DEVD706/G
      caspase-3 cleavage site. The cleavage of DSEB/RF-C140 is prevented by
      iodoacetamide and the specific caspase-3 inhibitor, tetrapeptide aldehyde Ac-DEVD
      CHO, but not by the specific ICE (interleukin-1-converting enzyme) inhibitors:
      CrmA and Ac-YVAD-CHO, indicating that the protease responsible for the cleavage
      of DSEB/RF-C140 during Fas-induced apoptosis in Jurkat cells is caspase-3, or a
      closely related protease. This conclusion is reinforced by the fact that
      recombinant caspase-3 but not caspase-1 reproduced the "in vivo" cleavage.
      Inasmuch as the cleavage of DSEB/RF-C140 separates its DNA binding from its
      association domain, required for replication complex formation, we propose that
      such a cleavage will impair DNA replication. Recent in vitro mutagenesis support
      this proposal (Uhlmann, F., Cai, J., Gibbs, E., O'Donnel, M., and Hurwitz, J.
      (1997) J. Biol. Chem. 272, 10058-10064).

PMID- 9235962
TI  - Ligation of CD40 activates interleukin 1beta-converting enzyme (caspase-1)
      activity in vascular smooth muscle and endothelial cells and promotes elaboration
      of active interleukin 1beta.
AB  - Inflammation contributes to a variety of arterial diseases including
      atherosclerosis. Interleukin 1beta (IL-1beta) in its activated mature 17-kDa form
      may mediate aspects of vascular inflammation. As shown previously, human vascular
      wall cells, such as smooth muscle cells (SMC), express the IL-1beta precursor
      upon stimulation and the IL-1beta-converting enzyme (ICE) constitutively but do
      not produce mature IL-1beta or express ICE activity. How SMC, the most numerous
      cell type in arteries, may release active IL-1beta has therefore remained a
      perplexing problem. We report here that stimulation of human vascular SMC and
      endothelial cells (EC) through CD40 ligand, a mediator recently localized in
      human atheroma, induced elaboration of the IL-1beta precursor as well as
      activation of cell-associated ICE. In addition to the constitutively expressed 45
      and 30-kDa immunoreactive ICE proteins, vascular cells incubated with
      recombinant human CD40 ligand (rCD40L) (but not IL-1 or TNF) showed an increase
      of a 20-kDa immunoreactive ICE protein by Western blot analysis. Furthermore, SMC
      and EC stimulated through rCD40L processed recombinant human IL-1beta precursor
      (pIL-1beta), generating a cleavage product of approximately 17 kDa. Appearance of
      both the 20-kDa immunoreactive ICE protein and pIL-1beta processing activity
      required at least 6 h of stimulation with 0.3 or 1.0 microg/ml rCD40L,
      respectively, and was inhibited by pre-incubation of the ligand with an anti
      CD40L antibody. Stimulation of vascular SMC and EC through rCD40L resulted in the
      release of biologically active IL-1beta, indicating processing of the native IL
      1beta precursor induced by the ligand. These findings establish a novel mechanism
      of IL-1beta activation in human vascular cells and, moreover, indicate a new
      pathway of ICE-activation, which could participate in inflammatory aspects of
      atherogenesis and other disease states.

PMID- 9235963
TI  - Transcriptional regulation of N-acetylglucosaminyltransferase V by the src
      oncogene.
AB  - Transformation of baby hamster kidney fibroblasts by the Rous sarcoma virus
      causes a significant increase in the GlcNAcbeta(1, 6)Man-branched
      oligosaccharides by elevating the activity and mRNA transcript levels encoding N
      acetylglucosaminyltransferase V (GlcNAc-T V). Elevated activity and mRNA levels
      could be inhibited by blocking cell proliferation with herbimycin A,
      demonstrating that Src kinase activity can regulate GlcNAc-T V expression. 5'
      RACE analysis was used to identify a 3-kilobase 5'-untranslated region from
      GlcNAc-T V mRNA and locate a transcriptional start site in a 25-kilobase pair
      GlcNAc-T V human genomic clone. A 6-kilobase pair fragment of the 5' region of
      the gene contained AP-1 and PEA3/Ets binding elements and, when co-transfected
      with a src expression plasmid into HepG2 cells, conferred src-stimulated
      transcriptional enhancement upon a luciferase reporter gene. This stimulation by
      src could be antagonized by co-transfection with a dominant-negative mutant of
      the Raf kinase, suggesting the involvement of Ets transcription factors in the
      regulation of GlcNAc-T V gene expression. The src-responsive element was
      localized by 5' deletion analysis to a 250-base pair region containing two
      overlapping Ets sites. src stimulation of transcription from this region was
      inhibited by co-transfection with a dominant-negative mutant of Ets-2,
      demonstrating that the effects of the src kinase on GlcNAc-T V expression are
      dependent on Ets.

PMID- 9235964
TI  - The traE gene of plasmid RP4 encodes a homologue of Escherichia coli DNA
      topoisomerase III.
AB  - The polypeptide encoded by the plasmid RP4 traE gene shows extensive protein
      sequence similarity to Escherichia coli topB, the gene encoding DNA topoisomerase
      III (Topo III). The traE gene product has been cloned into a bacteriophage T7
      based transient expression system, and the polypeptide has been expressed and
      purified. The TraE protein exhibits topoisomerase activity similar to that of
      Topo III. Relaxation is stimulated by high temperature and low concentrations of
      Mg2+. In addition, similar to E. coli Topo III, the TraE protein is a potent
      decatenase and can substitute for Topo III activity in vivo. The biochemical
      properties of the TraE protein in vitro suggest that the protein may be involved
      in the resolution of plasmid DNA replication intermediates either during
      vegetative replication or in conjugative DNA transfer. Putative homologues of
      Topo III have been found to be encoded by other broad host range, conjugative
      plasmids isolated from both Gram-negative and Gram-positive organisms, suggesting
      that Topo III-like polypeptides may have an essential role in the propagation of
      many promiscuous plasmids.

PMID- 9235965
TI  - Signal transduction pathways involved in the mitogenic activity of pleiotrophin.
      Implication of mitogen-activated protein kinase and phosphoinositide 3-kinase
      pathways.
AB  - Pleiotrophin (PTN) is a developmentally regulated protein which exhibits neurite
      outgrowth, mitogenic, and angiogenic properties. It has also been shown to be
      involved in tumor growth and metastasis. Here we used primary BEL (bovine
      epithelial lens) cells to investigate the signal transduction pathways involved
      in the mitogenic activity of recombinant PTN. PTN was purified from conditioned
      media of SW-13 cells transfected with the human PTN cDNA. We show that inhibitors
      of tyrosine kinase, mitogen-activated protein kinase, or phosphoinositide (PI) 3
      kinase inhibit DNA synthesis stimulated by PTN. Analysis of tyrosine
      phosphorylated proteins following PTN stimulation showed phosphorylation of two
      novel 190- and 215-kDa proteins in addition to SHC, ERK1, and ERK2. A mobility
      shift of phosphorylated ERK1 and ERK2 was detected with a panERK antibody
      confirming the phosphorylation of the two ERKs. Furthermore, in vitro
      immunocomplex kinase assay with Akt1, a natural substrate of PI 3-kinase, showed
      an activation of the kinase following PTN stimulation and a reversal by the PI 3
      kinase inhibitor wortmannin. We conclude that the mitogenic activity of PTN is
      dependent on tyrosine kinase activation and utilizes the mitogen-activated
      protein kinase and the PI 3-kinase pathways to transduce a mitogenic signal.

PMID- 9235967
TI  - Modulation of bradykinin receptor ligand binding affinity and its coupled G
      proteins by nitric oxide.
AB  - To determine whether nitric oxide (NO) can modulate bradykinin (BK) signaling
      pathways, we treated endothelial cells with an NO donor, S-nitrosoglutathione
      (GSNO), to determine its effect(s) on G-proteins (Gi and Gq) that are coupled to
      the type II kinin (BK2) receptor. Radioligand binding assays and Western analyses
      showed that GSNO (10-500 microM, 0-72 h) did not alter the expression of BK2
      receptor, Gi, or Gq. However, GSNO caused a 6-fold increase in basal cGMP
      production and decreased high affinity BK bindings sites and GTPase activity by
      74 and 85%, respectively. The cGMP analogue, dibutyryl-cGMP, also inhibited BK
      stimulated GTPase activity by 74% suggesting that some of the effects of NO may
      be mediated through activation of guanylyl cyclase. The NO synthase inhibitor,
      Nomega-monomethyl-L-arginine, inhibited endogenous NO synthase activity and cGMP
      production by 91 and 76%, respectively, but increased BK-stimulated GTPase
      activity by 61%. To determine which G-proteins are affected by NO, we performed
      GTP binding assays with [35S]GTPgammaS followed by immunoprecipitation with
      specific G-protein antisera. Both GSNO and dibutyryl-cGMP increased basal G
      protein GTP binding activities by 18-26%. However, GSNO decreased BK-stimulated
      Galphai2, Galphai3, and Galphaq/11 GTP binding activity by 93, 61, and 90%,
      respectively, whereas epinephrine-stimulated Galphas GTP binding activity was
      unaffected. These results suggest that NO can modulate BK signaling pathways by
      selectively inhibiting G-proteins of the Gi and Gq family.

PMID- 9235968
TI  - The WT1 protein is a negative regulator of the normal bcl-2 allele in t(14;18)
      lymphomas.
AB  - The translocated and normal bcl-2 alleles in the DHL-4 cell line with the
      t(14;18) translocation were separated by pulsed field electrophoresis. An in vivo
      footprint over a potential WT1 binding site in the bcl-2 5'-flanking sequence was
      identified on the normal silent allele. Electrophoretic mobility shift assays
      with the bcl-2 WT1 site demonstrated a single specific complex. UV cross-linking
      and Western analysis revealed that this gel shift complex contained WT1 protein.
      Deletion or mutation of the WT1 site resulted in an increase in activity of the
      bcl-2 promoter in DHL-4 cells. Cotransfection with a 3:1 ratio of a WT1
      expression vector to the bcl-2 promoter construct led to a 3.0-fold repression of
      the bcl-2 promoter. Cotransfection with a WT1 expression vector and the bcl-2
      promoter with the mutated WT1 site resulted in only 1.2-fold repression. We
      conclude that the WT1 site functions as a negative regulatory site for the normal
      silent bcl-2 allele in t(14;18) lymphomas. The WT1 site is not occupied on the
      translocated bcl-2 allele.

PMID- 9235969
TI  - Isolation and characterization of the protein components of the liver microsomal
      O2-insensitive NADH-benzamidoxime reductase.
AB  - Drugs containing strong basic nitrogen functional groups can be N-oxygenated to
      genotoxic products. While the reduction of such products is of considerable
      toxicological significance, most in vitro studies have focused on oxygen
      sensitive reductase systems. However, an oxygen-insensitive microsomal
      hydroxylamine reductase consisting of NADH, cytochrome b5, its reductase, and a
      third unidentified protein component has been known for some time (Kadlubar, F.
      F., and Ziegler, D. M. (1974) Arch. Biochem. Biophys. 162, 83-92). This report
      describes the isolation and identification of all of the components required for
      the reconstitution of an oxygen-insensitive liver microsomal system capable of
      catalyzing the efficient reduction of primary N-hydroxylated structures such as
      amidines, guanidines, amidinohydrazones, and similar functional groups. In
      addition to cytochrome b5 and its reductase, the reconstituted system requires
      phosphatidylcholine and a P450 isoenzyme that has been purified to homogeneity
      from pig liver. The participation of cytochrome b5 and NADH cytochrome b5
      reductase in cytochrome P450-dependent biotransformations has previously only
      been described for oxidative processes. The data presented suggest that this
      system may be an important catalyst in the reduction of genotoxic N-hydroxylated
      nitrogen components in liver. Their facile reduction by cellular NADH may be the
      reason why N-hydroxylated products can be missed by studies in vivo. Furthermore,
      the enzyme system is involved in the reduction of amidoximes and similar
      functional groups, which can be used as prodrug functionalities for amidines and
      related groups.

PMID- 9235973
TI  - The predischarge chromophore in bacteriorhodopsin: a 15N solid-state NMR study of
      the L photointermediate.
AB  - The L550 intermediate in the bacteriorhodopsin (bR) photocycle has drawn much
      attention with respect to the mechanism of light-driven proton transport because
      it selectively releases the Schiff base (SB) proton to the extracellular proton
      channel in the L-->M transition. Here we extend our solid-state NMR studies of bR
      photocycle intermediates to the L state. Under conditions that stabilize L550, a
      new SB signal is detected in the 15N NMR spectrum which disappears upon thermal
      relaxation. This signal is in the range for a protonated SB, but downfield from
      the SB signals of bR568 and N520. Since steric interactions would have the
      opposite effect on shielding, the data argue against a 13,14-dicis chromophore in
      L550. Comparison with the 15N chemical shifts of halide salts of protonated
      Schiff bases (pSB's) of retinal suggests that the interaction of the SB with its
      counterion is significantly stronger in L550 than in N520 (which in turn is
      stronger than in bR568). This is consistent with models of the early photocycle
      in which the electrostatic interaction between the SB and its counterion
      constitutes an important constraint. Although the L counterion interaction is
      comparable to that of a 6-s-trans,13-cis chloride salt, the visible spectrum is
      strongly red-shifted from the lambdamax = 491 nm of the chloride. This suggests
      some double bond strain in L550, particularly about the C=N bond. This strain is
      apparently gone in the N intermediate, which has a normal relationship between
      the 15N chemical shift and lambdamax. Such a relaxed chromophore is consistent
      with orientation of the SB proton toward the cytoplasmic surface in the N
      intermediate.

PMID- 9235966
TI  - Functional interaction of the auxilin J domain with the nucleotide- and substrate
      binding modules of Hsc70.
AB  - The uncoating of clathrin-coated vesicles requires the DnaJ homologue auxilin for
      targeting Hsc70 to clathrin coats. This function involves a transient interaction
      of the auxilin J domain with Hsc70. We have now identified the structural
      elements of Hsc70 that are responsible for the uncoating activity, and we show
      that the hitherto accepted view, which implicates the 10-kDa carboxyl-terminal
      variable domain of Hsc70, is incorrect. A 60-kDa chymotryptic or analogous
      recombinant fragment of Hsc70, which contains the ATPase- and substrate-binding
      domains, is sufficient to liberate clathrin from coated vesicles. Consistent with
      this was the observation that Hsp70 uncoats coated vesicles with the same
      efficacy as Hsc70 and that DnaK possesses vestigial uncoating activity. Direct
      binding studies demonstrated that the auxilin J domain undergoes an ATP-dependent
      reaction only with fragments of Hsc70 that contain both the ATPase- and substrate
      binding domains. The individual domains by themselves did not bind to the J
      domain nor did a recombinant protein that contained the substrate-binding domain
      attached to the 10-kDa variable domain.

PMID- 9235972
TI  - Electrogenicity of electron and proton transfer at the oxidizing side of
      photosystem II.
AB  - The electrogenicity of electron and proton transfer at the oxidizing side of PSII
      was monitored by transmembrane electrochromism of carotenoids in thylakoids and,
      independently, by electrometry in oxygen-evolving photosystem II core particles.
      It yielded dielectrically weighted distances between cofactors. They were related
      to the one between YZox and QA- (=100%). The electron transfer from YZ to P680+
      ranged over a relative distance of 15%, while the one from Mn4 to YZox ranged
      over less than 3.5%. The latter result placed Mn4 and YZ at about the same
      weighted depth in the membrane. The oxidation of cofactor X by YZox during S2 -->
      S3 ranged over 10%. We tentatively attributed 7% to proton transfer into the
      lumen and 3% to electron transfer, in line with our notion that one proton is
      liberated from Xox itself. This placed X at the same depth in the membrane as Mn.
      Proton release upon the final oxidation of water during the oxygen-evolving step
      S4 --> S0 revealed relative electrogenic components of 5.5% in core particles and
      between 10.5% (pH 7.4) and 2% (pH 6.2) in thylakoids. The former likely reflected
      proton transfer from bound water into the lumen and the latter to intraprotein
      bases that were created in the foregoing transitions. A tentative scheme for the
      arrangement of cofactors at the oxidizing side of photosystem II is presented.

PMID- 9235974
TI  - Effects of decyl-aurachin D and reversed electron transfer in cytochrome bd.
AB  - Decyl-aurachin D is a near-stoichiometric inhibitor of cytochrome bd from
      Azotobacter vinelandii. Interaction of decyl-aurachin D with the oxidase induces
      a redshift of the alpha-band and Soret band of a b-type cytochrome, probably b
      558, suggesting close proximity of the inhibitor binding site to this haem and
      hence to the proposed quinol binding domain. The compound does not affect the
      oxygen binding site directly as judged from unchanged CO recombination kinetics
      to haem d in dithionite-reduced enzyme. Although in the presence of ubiquinol-1 a
      decyl-aurachin D containing sample generates levels of haem reduction and
      catalytic intermediates similar to the control, the approach to this steady state
      is severely inhibited. In addition to the spectral effect on b-558, decyl
      aurachin D raises the midpoint potential of haem b-558, but also lowers that of
      haem b-595. Consistent with the shift in midpoint potentials, electron backflow
      from haem d to the b-type haems can be observed in decyl-aurachin D inhibited
      samples following photolysis of the mixed-valence CO-ligated form of the enzyme.
      The data show that decyl-aurachin D acts on the donor side of haem b-558 without
      substantially affecting internal electron transfer rates or the oxygen reduction
      site.

PMID- 9235971
TI  - A Kaposi's sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6)
      activates signaling through the shared gp130 receptor subunit.
AB  - The present studies analyzed the biologic activity of a gene product (vIL-6)
      encoded by the recently discovered Kaposi's sarcoma-associated herpesvirus (KSHV)
      bearing 24.8% amino acid identity with human interleukin-6 (huIL-6). Based on
      this similarity, we hypothesized that this viral homolog might trigger the
      JAK/STAT pathway, which typically is engaged by IL-6 and other cytokines.
      Activation of receptor-associated Janus tyrosine kinases (JAKs) results in the
      subsequent phosphorylation of signal transducers and activators of transcription
      (STATs) leading to nuclear entry and transcriptional regulation of target genes.
      Treatment of HepG2 cells with culture medium containing recombinant KSHV-encoded
      vIL-6 led to rapid induction of JAK1 phosphorylation and a nuclear DNA-binding
      activity found to contain STAT1 and STAT3. An antibody to the IL-6 receptor (IL
      6R) alpha subunit effectively neutralized the response to huIL-6 but failed to
      block STAT activation by vIL-6. In contrast, an antibody reactive with the gp130
      subunit of IL-6R abrogated signaling of both responses. Moreover, a transfected
      cell line expressing human gp130 without IL-6Ralpha exhibited a robust response
      to vIL-6 but not to huIL-6. These results demonstrate that KSHV encodes a
      cytokine that activates specific JAK/STAT signaling via interactions with the
      gp130 signal transducing subunit independently of the IL-6Ralpha chain. This
      activity may have an impact on gp130-mediated signaling in response to native
      cytokines and thereby influence disease pathogenesis upon KSHV infection.

PMID- 9235977
TI  - Mechanism of the oxidation of 3,5,3',5'-tetramethylbenzidine by myeloperoxidase
      determined by transient- and steady-state kinetics.
AB  - Earlier investigations of the oxidation of 3,5,3',5'-tetramethylbenzidine (TMB)
      using horseradish peroxidase and prostaglandin H-synthase have shown the
      formation of a cation free radical of TMB in equilibrium with a charge-transfer
      complex, consistent with either a two- or a one-electron initial oxidation. In
      this work, we exploited the distinct spectroscopic properties of myeloperoxidase
      and its oxidized intermediates, compounds I and II, to establish two successive
      one-electron oxidations of TMB. By employing stopped-flow techniques under
      transient-state and steady-state conditions, we also determined the rate
      constants for the elementary steps of the myeloperoxidase-catalyzed oxidation of
      TMB at pH 5.4 and 20 degrees C. The second-order rate constant for compound I
      formation from the reaction of native enzyme with H2O2 is 2.6 x 10(7) M-1 s-1.
      Compound I undergoes a one-electron reduction to compound II in the presence of
      TMB, and the rate constant for this reaction was determined to be (3.6 +/- 0.1) x
      10(6) M-1 s-1. The spectral scans show that compound II accumulates in the steady
      state. The rate constant for compound II reduction to native enzyme by TMB
      obtained under steady-state conditions is (9.4 +/- 0.6) x 10(5) M-1 s-1. The
      results are applied to a new, more accurate assay for myeloperoxidase based upon
      the formation of the charge-transfer complex between TMB and its diimine final
      product.

PMID- 9235976
TI  - Mechanistic role of an NS4A peptide cofactor with the truncated NS3 protease of
      hepatitis C virus: elucidation of the NS4A stimulatory effect via kinetic
      analysis and inhibitor mapping.
AB  - Infection by hepatitis C viruses (HCVs) is a serious medical problem with no
      broadly effective treatment available for the progression of chronic hepatitis.
      The catalytic activity of a viral serine protease located in the N-terminal one
      third of nonstructural protein 3 (NS3) is required for polyprotein processing at
      four site-specific junctions. The three-dimensional crystal structure of the NS3
      NS4A co-complex [Kim, J. L., Morgenstern, K. A., Lin, C., Fox, T., Dwyer, M. D.,
      Landro, J. A., Chambers, S. P., Markland, W., Lepre, C. A., O'Malley, E. T.,
      Harbeson, S. L., Rice, C. M., Murcko, M. A., Caron, P. R., & Thomson, J. A.
      (1996) Cell 87, 343-355] delineates a small hydrophobic region within the 54
      residue NS4A protein that intercalates with and makes extensive contacts to the
      core of the protease. The current investigation addresses the mechanism of NS3
      protease catalytic activation by NS4A utilizing a small synthetic NS4A peptide
      (residues 1678-1691 of the virus polyprotein sequence) and the recombinantly
      expressed protease domain of NS3. The addition of NS4A dramatically increased NS3
      kcat and kcat/Km catalytic parameters when measured against small peptide
      substrates representing the different site-specific junctions of the polyprotein.
      The catalytic effect of natural and non-natural amino acid substitutions at the
      P1 position in a 5A/5B peptide substrate was investigated. NS3-NS4A demonstrated
      a marked catalytic preference for the cysteine residue commonly found in
      authentic substrates. The pH dependence of the NS3 hydrolysis reaction is not
      affected by the presence of NS4A. This result suggests that NS4A does not change
      the pKa values of the active site residues of NS3 protease. A steady state
      kinetic analysis was performed and indicated that the binding of NS4A and the
      peptide substrate occurs in an ordered fashion during the catalytic cycle, with
      NS4A binding first. Two distinct kinetic classes of peptidyl inhibitors based
      upon the 5A/5B cleavage site were identified. An NS4A-independent class is devoid
      of prime residues. A second class of inhibitors is NS4A-dependent and contains a
      natural or non-natural cyclic amino acid substituted for the commonly found P1'
      residue serine. These inhibitors display an up to 80-fold increase in affinity
      for NS3 protease in the presence of NS4A. Sequential truncation of prime and P
      residues from this inhibitor class demonstrated the fact that the P4' and P1'
      residues are crucial for potent inhibition. The selectivity of this NS4A effect
      is interpreted using a model of the 5A/5B decapeptide substrate bound to the
      active site of the NS3-NS4A structure.

PMID- 9235975
TI  - Characterization of a partially unfolded high potential iron protein.
AB  - A partially unfolded state of the Fe4S4-containing high potential iron-sulfur
      protein from Chromatium vinosum has been detected and characterized by NMR
      spectroscopy following addition of a concentrated solution of guanidinium
      chloride to the native protein. This intermediate species (i) maintains the
      polymetallic center, (ii) exhibits a largely collapsed secondary structure, and
      (iii) undergoes fast cluster decomposition upon oxidation. This information is
      framed into the knowledge about this class of proteins, and the possible role of
      this intermediate with respect to the in vivo folding/unfolding process is
      discussed as well its role in the slow hydrolytic degradation characteristic of
      oxidized HiPIPs.

PMID- 9235978
TI  - EPR investigation of compound I in Proteus mirabilis and bovine liver catalases:
      formation of porphyrin and tyrosyl radical intermediates.
AB  - Compound I of Proteus mirabilis and bovine liver catalases (PMC and BLC,
      respectively) were studied combining EPR spectroscopy and the rapid-mix freeze
      quench techniques. Both enzymes, when treated with peroxyacetic acid, form a
      catalytic intermediate which consists of an oxoferryl porphyrin pi-cation
      radical. In PMC this intermediate is semistable, and an unexpected reversible
      equilibrium under pH influence takes place between two forms of compound I with
      different coupling between the oxoferryl and the porphyrin pi-cation radical. At
      acid pH, one form has a ferromagnetic character as in Micrococcus luteus compound
      I. At neutral pH, another form with a much smaller coupling, reminiscent of the
      horse radish peroxidase compound I, is detected. The approximate midpoint,
      estimated for these changes in the range 5.3 < pH < 6.0, approaches the pKa value
      of an histidyl residue. The residues possibly involved in the transformation are
      discussed in terms of the known structure of PMC compound I. The EPR spectrum of
      BLC compound I (pH 5.6), obtained in the millisecond time scale (40 ms), also
      showed a mixture of two forms which, most probably, correspond to two different
      magnetic exchange interactions, as in the case of PMC. Taken together, the low
      temperature electronic absorption and the EPR spectra of BLC compound I formed in
      the 0.04-15 s range show that the porphyrin pi-cation radical disappears and,
      instead, a tyrosyl radical is formed. ENDOR experiments confirm our previously
      estimated hyperfine couplings to the C2,6 and C3,5 ring protons and the beta
      methylene protons of the purported tyrosyl radical. Candidates for such a tyrosyl
      radical are discussed in connection with the possible electron transfer pathways
      between the heme active site and the NADPH cofactor.

PMID- 9235970
TI  - Rotation of a gamma-epsilon subunit domain in the Escherichia coli F1F0-ATP
      synthase complex. The gamma-epsilon subunits are essentially randomly distributed
      relative to the alpha3beta3delta domain in the intact complex.
AB  - A triple mutant of Escherichia coli F1F0-ATP synthase,
      alphaQ2C/alphaS411C/epsilonS108C, has been generated for studying movements of
      the gamma and epsilon subunits during functioning of the enzyme. It includes
      mutations that allow disulfide bond formation between the Cys at alpha411 and
      both Cys-87 of gamma and Cys-108 of epsilon, two covalent cross-links that block
      enzyme function (Aggeler, R., and Capaldi, R. A. (1996) J. Biol. Chem. 271, 13888
      13891). A cross-link is also generated between the Cys at alpha2 and Cys-140 of
      the delta subunit, which has no effect on functioning (Ogilvie, I., Aggeler, R.,
      and Capaldi, R. A. (1997) J. Biol. Chem. 272, 16652-16656). CuCl2 treatment of
      the mutant alphaQ2C/alphaS411C/epsilonS108C generated five major cross-linked
      products. These are alpha-gamma-delta, alpha-gamma, alpha-delta-epsilon, alpha
      delta, and alpha-epsilon. The ratio of alpha-gamma-delta to the alpha-gamma
      product was close to 1:2, i.e. in one-third of the ECF1F0 molecules the gamma
      subunit was attached to the alpha subunit at which the delta subunit is bound.
      Also, 20% of the epsilon subunit was present as a alpha-delta-epsilon product.
      With regard to the delta subunit, 30% was in the alpha-gamma-delta, 20% in the
      alpha-delta-epsilon, and 50% in the alpha-delta products when the cross-linking
      was done after incubation in ATP + MgCl2. The amounts of these three products
      were 40, 22, and 38%, respectively, in experiments where Cu2+ was added after
      preincubation in ATP + Mg2+ + azide. The delta subunit is fixed to, and therefore
      identifies, one specific alpha subunit (alphadelta). A distribution of the gamma
      and epsilon subunits, which is essentially random with respect to the alpha
      subunits, can only be explained by rotation of gamma-epsilon relative to the
      alpha3beta3 domain in ECF1F0.

PMID- 9235979
TI  - Subunit structure and function of porcine factor Xa-activated factor VIII.
AB  - Factor Xa and thrombin (factor IIa) activate factor VIII (fVIII) by different
      proteolytic pathways. Thrombin cleaves fVIII at Arg372 between the A1 and A2
      domains, at Arg740 between the A2 and B domains, and at Arg1689 between the B and
      A3 domains to form an A1/A2/A3-C1-C2 heterotrimer. We now report a stable porcine
      fVIIIaXa preparation obtained by Mono S HPLC at pH 6. NH2-terminal sequence
      analysis of purified subunits of fVIIIaXa revealed that factor Xa cleaves fVIII
      at Arg219 within the A1 domain and at Arg490 within the A2 domain, as well as at
      Arg372, Arg740, and Arg1689. Analytical ultracentrifugation of the fVIIIaXa
      preparation yielded results consistent with a single, 148 kDa species, similar to
      previous results with fVIIIaIIa [Lollar, P., & Parker, C. G. (1989) Biochemistry
      28, 666-674]. Thus, the major species in the fVIIIaXa preparation contains five
      subunits, including fragments of the A1 and A2 domains that remain noncovalently
      bound. Fluorescence anisotropy measurements indicated there was no difference in
      the affinity of fVIIIaXa and fVIIIaIIa for a fluorescent dye-labeled, active-site
      blocked derivative of porcine factor IXa. Additionally, the fVIIIaXa preparation
      bound dye-labeled factor IXa with 1:1 stoichiometry, indicating that all fVIIIaXa
      molecules in the preparation can bind factor IXa. However, fVIIIaXa had 4-fold
      less procoagulant activity than fVIIIaIIa. Kinetic analysis of fVIIIa cofactor
      activity using purified factor IXa and factor X suggested this difference is due
      to greater activity of fVIIIaIIa relative to fVIIIaXa within the intrinsic fXase
      complex, rather than a difference in their stabilities.

PMID- 9235981
TI  - Localization of an effective fibrin beta-chain polymerization site: implications
      for the polymerization mechanism.
AB  - To examine whether fibrin N-terminal Aalpha 17-23 and Bbeta 15-25 may contain
      high-affinity polymerization sites, GPRVVER and GHRPLDKKREE analogs were
      prepared, and their abilities to inhibit fibrin monomers from repolymerizing were
      compared in turbidity and clottability assays. Within Aalpha 17-23, GPR is the
      most active site (IC30 of 0.95-1.36 mM). Its extension into GPRVVER (IC30 of 1.75
      2.3 mM) reduced activity. Within Bbeta 15-25, acyl-DKKREE (IC30 of 0.30-0.53 mM)
      can account for GHRPLDKKREE activity (IC30 of 0. 33-0.44 mM). Comparison of the
      assays showed that calcium, whose presence induces thick fibrin fibers, elicited
      a higher turbidity than clottability inhibition. Similarly, the lateral
      association-promoting GHRP (IC30 of 1.25-1.43 mM) gave a high turbidity vs
      clottability inhibition ratio (137%). In contrast, low ratios were found for the
      linear-association-initiating GPR (73%) and for acyl-DKKREE (34%). Structure
      activity correlation showed that fibrinogen-like acyl-GPRP and acyl-GHRP could
      inhibit D. E association at the millimolar range, but in a manner different from
      fibrin-related GPR peptides did, which required the NH2 as well as Arg presence.
      To explain Bbeta 20-25 masking, it is proposed that DKKREE in fibrinogen may
      engage in ionic and hydrogen bonds with KDSDW, the Aalpha 29-33 sequence
      implicated in thrombin binding. To explain acyl-GPRP and acyl-GHRP inhibition of
      D.E association, it is proposed that fibrinogen packing may be mediated by E
      domain association with alphaC (Aalpha 220-609) fragments of adjacent molecules,
      and by alphaC-alphaC association. A modified polymerization mechanism is deduced
      by taking into account fibrinogen N-terminal conformation as well as E domain
      binding to thrombin vs alphaC fragments. This model proposes the following. (1)
      Upon thrombin binding to fibrinogen KDSDW, DKKREE may become exposed. (2)
      Fibrinopeptide A cleavage further unmasks the NH2 and Arg group of GPR, leading
      to DKKREE and GPR initiation of polymerization. (3) The micromolar-effective
      thrombin-fibrin(ogen) binding may initiate a partial alphaC repulsion. Subsequent
      DKKREE and GPR binding to D domains of other fibrin(ogen) will lead to the
      formation of the trimer and bring additional molecules to fibrin N-terminal
      region, and the combined steric congestion may lead to a complete alphaC
      repulsion from the overcrowded E domain. (4) Repulsion of the large Aalpha 220
      609 fragments may unmask multiple polymerization sites beyond the fibrin N
      terminal region.

PMID- 9235980
TI  - High-affinity binding of the neonatal Fc receptor to its IgG ligand requires
      receptor immobilization.
AB  - The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the
      acquisition of passive immunity by the fetus or newborn. In adult mammals, FcRn
      also binds IgG and returns it to the bloodstream, thus protecting IgG from a
      default degradative pathway. Biosensor assays have been used to characterize the
      interaction of a soluble form of FcRn with IgG. We use the statistical method of
      cross-validation to show that there are two classes of noninteracting binding
      sites, and these are sufficient to account for previously observed nonlinear
      Scatchard plots of FcRn/IgG binding data. We demonstrate that immobilization of
      FcRn on the biosensor surface reproduces the high-affinity IgG binding observed
      for membrane-bound FcRn, whereas immobilization of IgG results in lower affinity
      binding similar to that of the FcRn/IgG interaction in solution. The dependence
      of FcRn/IgG binding affinity on the coupled molecule provides further evidence in
      support of the previously hypothesized model that an FcRn dimer forms the high
      affinity IgG binding site.

PMID- 9235982
TI  - Inhibition of Lyn function in mast cell activation by SH3 domain binding
      peptides.
AB  - While Lyn tyrosine kinase has been shown to be necessary for IgE-receptor
      (FcepsilonRI)-mediated mast cell activation, the mechanism of Lyn activation is
      not yet understood. Using a micro-electroporation technique to quantitatively
      introduce peptides into the cytosol of tumor mast cells, we show that proline
      rich peptides that preferentially bind Src family SH3 domains block receptor
      induced repetitive calcium spikes in a concentration dependent manner. The Src
      family member Lyn was the likely target, since a series of phage displaying
      derived peptides with increased Lyn SH3 domain binding specificity inhibited
      FcepsilonRI-mediated calcium signaling at concentrations consistent with binding
      to Lyn rather than other Src-type kinases. Furthermore, SH3 binding peptides
      prevented the plasma membrane translocation of a fluorescently labeled Syk tandem
      SH2 domain, which binds to phosphorylated FcepsilonRI, suggesting that the
      peptides specifically block the Lyn-mediated step by which FcepsilonRI cross
      linking leads to receptor phosphorylation. Our study suggests that the binding of
      proline-rich peptides, or corresponding cellular interaction partners, to Lyn SH3
      domain suppresses the Lyn-mediated phosphorylatation of FcepsilonRI and calcium
      signaling.

PMID- 9235983
TI  - Identification and characterization of functional cation coordination sites in
      platelet endothelial cell adhesion molecule-1.
AB  - We have employed 45CaCl2 binding studies, terbium (Tb3+) luminescence
      spectroscopy, and electrospray mass spectroscopy (ESI-MS) to identify divalent
      metal binding properties of soluble recombinant human PECAM-1 (srPECAM-1), and to
      define unique cation binding domains using short, linear peptide sequences from
      the protein. PECAM-1 was found to directly interact with 45CaCl2, binding 2.3
      nmol of Ca2+/nmol of srPECAM-1 with a Kd of 1.17 nM. PECAM-1 was found to contain
      high-affinity cation binding sites involving amino acids Asp443, Asp444, and
      Glu446 of Ig-domain 5 and residues Glu487, Glu490, Asp491, Glu538, Glu540, and
      Glu542 of Ig-domain 6. The PECAM cation binding sites demonstrated broad
      specificity for all divalent cations, with Mn2+ having a higher affinity than
      Ca2+ or Mg2+. Direct binding of Tb3+ to these PECAM peptides was confirmed by ESI
      MS. Modeling studies predict that the six cation binding residues within Ig
      domain 6 are proximal to each other in three-dimensional space, and may form a
      single cation coordination site. The identification of cation binding sites in
      PECAM-1 will direct further work in examining its cation-dependent roles in
      cellular signaling.

PMID- 9235984
TI  - Closed form of liganded glutamine-binding protein by rotational-echo double
      resonance NMR.
AB  - Rotational-echo double-resonance NMR has been used to determine internuclear
      distances in the complex of glutamine-binding protein and its ligand, l
      glutamine. The distances between the ligand and Tyr185 are consistent with the
      results of molecular dynamics simulations constrained by three REDOR-determined
      distances to His156. This model is also consistent with six other REDOR
      determined internuclear distances, most of which agree with values from the first
      report of an X-ray structure of the complex of glutamine-binding protein and l
      glutamine.

PMID- 9235985
TI  - Solution structures of the R6 human insulin hexamer,.
AB  - The three-dimensional solution structure of the phenol-stabilized 36 kDa R6
      insulin hexamer was determined by NMR spectroscopy and restrained molecular
      dynamics. The hexamer structures were derived using a stepwise procedure.
      Initially, 60 monomers were obtained by distance geometry from 665 NOE-derived
      distance restraints and three disulfide bridges. Subsequently, the hexamer
      structures were calculated by simulated annealing, using 30 hexamers constructed
      from the best 36 monomer structures as the starting models. The NMR data show
      that the aromatic ring of residue Phe(B25) can take two different orientations in
      the solution hexamer: one in which it points inward (molecule 1, about 90%) and
      one in which it points outward from the surface of the monomer (molecule 2, about
      10%). Therefore, two hexamer structures were calculated: a symmetric hexamer
      consisting of six molecule 1 monomers and a nonsymmetric hexamer consisting of
      five molecule 1 monomers and one molecule 2 monomer. For each of the six
      monomers, the restraints used in the calculations of the hexamer structures
      include, in addition to the intramonomeric restraints, 25 NOEs between insulin
      and phenol, 23 NOEs and two hydrogen bonds across the dimer interface, nine NOEs
      across the trimer interface, and five intramonomeric or two intermonomeric NOEs,
      respectively, specifying the different orientations of the Phe(B25) ring. The
      coordination of the two Zn atoms was defined by eight distance restraints. Thus,
      a total of 4394 and 4391 distance restraints, respectively, were used in the two
      hexamer calculations. The NOE restraints were classified in an iterative process
      as intra- or intermonomeric on the basis of their consistency or inconsistency
      with the structure of the monomer. The assignment of the dimer- and trimer
      specific NOEs was made using the crystal structure of the R6 hexamer as the
      starting model. For both solution hexamers, the average backbone rms deviation is
      0.81 A, if the less well-defined N- and C-terminal residues are excluded. The
      corresponding rms deviations for all heavy atoms are 1.17 and 1.19 A for the
      nonsymmetric and symmetric hexamer, respectively. The overall solution structure
      of the R6 insulin hexamer is compact, rigid, and symmetric and resembles the
      corresponding crystal structure. However, the extension of the B-chain alpha
      helix, which characterizes the R state, is shorter in the solution structure than
      in the crystal structure. Also, the study shows that the orientation of the
      Phe(B25) ring has no effect on the structure of the rest of the molecule, within
      the uncertainty of the structure determination. The importance of these findings
      for the current model for the insulin-receptor interaction is discussed.

PMID- 9235986
TI  - Mapping the regions of the complement inhibitor CD59 responsible for its species
      selective activity.
AB  - CD59 is a widely distributed membrane-bound glycoprotein that inhibits the
      formation of the cytolytic membrane attack complex (MAC) of complement on host
      cells. CD59 from different species varies in its capacity to inhibit heterologous
      complement, and this species selective function of CD59 contributes to the
      phenomenon of homologous restriction. Here, we demonstrate that human CD59 is not
      an effective inhibitor of rat complement, although rat CD59 inhibits rat and
      human complement equally well. By constructing human-rat CD59 chimeric proteins,
      we have mapped the residues important in conferring human CD59 species
      selectivity to two regions; 40-47 and 47-66 in the primary structure. Analysis of
      a model of the molecular surface of human CD59 revealed that residues 40-66
      mapped to a region in the three-dimensional structure that surrounds residues
      previously identified as important for CD59 function.

PMID- 9235987
TI  - Synthesis, stereochemistry, and biological activity of 1alpha,23,25-trihydroxy-24
      oxovitamin D3, a major natural metabolite of 1alpha,25-dihydroxyvitamin D3.
AB  - The C(23) epimers of 1alpha,23,25(OH)3-24-oxovitamin D3, a major natural
      metabolite of the secosteroid hormone, 1alpha,25(OH)2D3, were chemically
      synthesized for the first time. The metabolite was synthesized by palladium
      coupling of the appropriate CD ring analog with an A ring enyne. Various
      approaches from quinic acid to the A ring precursors were explored, and a new
      route to the A ring enyne from quinic acid was developed. The C(23)
      stereochemistry of the natural 1alpha,23,25(OH)3-24-oxovitamin D3 produced in
      neonatal human keratinocytes was determined to be S on the basis of the 1H NMR
      and the HPLC data. The biological activity of 1alpha,23(S), 25(OH)3-24-oxovitamin
      D3 in primary cultures of bovine parathyroid cells was determined by comparing
      the potency of this metabolite to that of 1alpha,25(OH)2D3 in suppression of
      parathyroid hormone (PTH) secretion. The results indicate that 1alpha,23(S),
      25(OH)3-24-oxovitamin D3 potently suppressed PTH secretion even at concentrations
      as low as 10(-)12 M and is equipotent with 1alpha, 25(OH)2D3. The high activity
      of 1alpha,23(S),25(OH)3-24-oxovitamin D3 cannot be explained on the basis of its
      affinity for the vitamin D receptor as this metabolite was found to be 10 times
      less effective than radioinert 1alpha,25(OH)2D3 in blocking the uptake and
      receptor binding of [3H]-1alpha,25(OH)2D3 in intact parathyroid cells. Further
      studies are required to explain the molecular basis for the activity of
      1alpha,23(S),25(OH)3-24-oxovitamin D3 in its ability to suppress PTH secretion.
      In summary, our present study indicates that the C(23) stereochemistry of the
      natural 1alpha,23, 25(OH)3-24-oxovitamin D3 is S and this metabolite is
      equipotent to 1alpha,25(OH)2D3 in suppressing PTH secretion.

PMID- 9235988
TI  - The comparative interaction of quinonoid (6R)-dihydrobiopterin and an alternative
      dihydropterin substrate with wild-type and mutant rat dihydropteridine
      reductases.
AB  - Kinetic parameters and primary deuterium isotope effects have been determined for
      wild-type dihydropteridine reductase (EC 1.6.99.7) and the Ala133Ser, Lys150Gln,
      Tyr146His, Tyr146Phe single, and Tyr146Phe/Ala133Ser and Tyr146Phe/Lys150Gln
      double mutant enzyme forms using the natural substrate, quinonoid (6R)-l-erythro
      dihydrobiopterin (qBH2) and an alternate substrate, quinonoid 6,7
      dimethyldihydropteridine (q-6,7-diMePtH2). Mutation at either Tyr146 or Lys150
      resulted in pronounced changes in kinetic parameters and isotope effects for both
      pterin substrates, confirming a critical role for these residues in enzyme
      mediated hydride transfer. By contrast, the Ala133Ser mutant was practically
      indistinguishable from wild-type enzyme. The changes observed, however, were
      quite different for the two pterin substrates. Thus, kcat for q-6,7-diMePtH2
      decreased across the series of mutants from a value of 150 s-1 for wild-type
      enzyme to essentially zero activity for the Tyr146Phe/Lys150Gln double mutant.
      Conversely, kcat for qBH2 increased 3-11-fold across the same series of mutants
      from the wild-type value of 23 s-1. For both pterin substrates, the Km (KPt)
      increased several orders of magnitude upon mutation of Tyr146 or Lys150, with the
      greater relative increase using qBH2. Significant primary deuterium isotope
      effects on kcat (Dkcat) and kcat/KPt (D(kcat/KPt)) observed for the Tyr146 and
      Lys150 mutants varied depending on the pterin substrate used and ranged up to a
      maximum value of 5.5-6. For qBH2, where Dkcat < Dkcat/KPt was consistently
      observed, the rate determining step is ascribed to release of the
      tetrahydropterin product. For q-6,7-diMePtH2, where in all cases Dkcat =
      Dkcat/KPt, catalysis is probably limited by an isomerization step occurring prior
      to hydride transfer. Modeling studies in which qBH2 was docked into the binary
      E:NADH complex provide a structural rationale for the observed differences
      between the two pterin substrates. The natural substrate, qBH2, displays a higher
      affinity for the enzyme active site, presumably due to interaction of the
      dihydroxypropyl side chain of the substrate with a polar loop of residues
      containing Asn186, Ser189, and Met190. The location of this loop within the three
      dimensional structure is consistent with putative substrate binding loops for
      other members of the short chain dehydrogenase/reductase (SDR) family, which
      includes dihydropteridine reductase.

PMID- 9235989
TI  - A new non-heme iron environment in Paracoccus denitrificans adenylate kinase
      studied by electron paramagnetic resonance and electron spin echo envelope
      modulation spectroscopy.
AB  - Adenylate kinase from the Gram-negative bacterium Paracoccus denitrificans
      (AKden) has structural features highly similar to those of the enzyme from Gram
      positive organisms. Atomic absorption spectroscopy of the recombinant protein,
      which is a dimer, revealed the presence of two metals, zinc and iron, each
      binding most probably to one monomer. Under oxidizing conditions, the electron
      paramagnetic resonance (EPR) spectrum of AKden at 4.2 K consists of features at g
      = 9.23, 4.34, 4.21, and 3.68. These features are absent in the ascorbate-reduced
      protein and are characteristic of a S = 5/2 spin system in a rhombic environment
      with E/D = 0.24 and are assigned to a non-heme Fe3+ (S = 5/2) center. The zero
      field splitting parameter D (D = 1.4 +/- 0.2 cm-1) was estimated from the
      temperature dependence of the EPR spectra. These EPR characteristic as well as
      the difference absorption spectrum (oxidized minus reduced) of AKden are similar
      to those reported for the non-heme iron protein rubredoxin. Nevertheless, the
      redox potential of the Fe2+/Fe3+ couple in AKden was measured at +230 +/- 30 mV,
      which is more positive than the redox potential of the non-heme iron in
      rubredoxin. Binding of cyanide converts the iron from the high-spin (S = 5/2) to
      the low-spin (S = 1/2) spin state. The EPR spectrum of the non-heme Fe3+(S = 1/2)
      in the presence of cyanide has g values of 2.45, 2.18, and 1.92 and spin
      Hamiltonian parameters R/lambda = 7. 4 and R/mu = 0.56. The conversion of the non
      heme iron to the low-spin (S = 1/2) state allowed the study of its local
      environment by electron spin echo envelope modulation spectroscopy (ESEEM). The
      ESEEM data revealed the existence of 14N or 15N nuclei coupled to the low-spin
      iron after addition of KC14N or KC15N respectively. This demonstrated that iron
      in AKden has at least one labile coordination position that can be easily
      occupied by cyanide. Other possible magnetic interactions with nitrogen(s) from
      the protein are discussed.

PMID- 9235990
TI  - pH dependence and structural interpretation of the reactions of Coprinus cinereus
      peroxidase with hydrogen peroxide, ferulic acid, and 2,2'-azinobis.
AB  - Steady-state and transient-state analysis of Coprinus cinereus peroxidase, CIP
      (identical to Arthromyces ramosus peroxidase), was used to characterize the
      kinetics of the three fundamental steps in heme peroxidase catalysis: compound I
      (cpd I) formation, cpd I reduction, and compound II (cpd II) reduction. The rate
      constant k1 for cpd I formation determined by transient-state analysis is (9.9 +/
      0.6) x 10(6) M-1 s-1. The k1 determined by steady-state analysis is (8.8 +/-
      0.6) x 10(6) M-1 s-1 in the presence of ferulic acid and (6.7 +/- 0.2) x 10(6) M
      1 s-1 in the presence of ABTS. The value of k1 is constant from pH 6 to 11.
      However, at low pH the value of k1 decreases, corresponding to titration of an
      enzyme group with a pKa of 5.0. Titration of this group is also detected from
      cyanide-binding kinetics. Furthermore, titration of this group is linked with
      marked spectroscopic changes unique to CIP. We ascribe these changes to
      protonation of proximal His183. A very low pKa is proposed for distal His55 in
      the resting state of CIP. The rate constants, k2 for cpd I and k3 for cpd II
      reduction, are very large for both ferulic acid and 2,2'-azinobis(3
      ethylbenzthiazoline-6-sulfonic acid) (ABTS). For ferulic acid, transient-state
      kinetic analysis shows that the values of k2 and k3 are identical at pH 5-6, and
      the ratio k2/k3 increases to 10 at pH 10. The similar magnitude of k2 and k3 is
      unusual for a peroxidase. Both k2 and k3 decrease with increasing pH, and both
      are influenced by two ionizations: one with a pKa value near 7, assumed to
      reflect the protonation of His55; and the other with pKa of 9.0 +/- 0.7 for k2
      and 8.8 +/- 0.4 for k3, perhaps reflecting the phenol-linked deprotonation of
      ferulic acid. Steady-state analysis at pH 7.0 gave k2k3/(k2 + k3) = (2.2 +/- 0.1)
      x 10(7) M-1 s-1 for ferulic acid, and (2.0 +/- 0.7) x 10(7) M-1 s-1 for ABTS and
      revealed a unimolecular step with ku = 1500 s-1, ascribed to slow ABTS radical
      product release. From transient-state results at pH 7, the values of k2 and k3
      were found to be identical also for ABTS. A mechanism for cpd I and II reduction
      involving distal histidine and arginine is proposed.

PMID- 9235991
TI  - Reductive half-reaction of thioredoxin reductase from Escherichia coli.
AB  - Thioredoxin reductase is a homodimeric flavoenzyme containing a flavin adenine
      dinucleotide (FAD) and a redox-active disulfide in each subunit. Structural work
      on the enzyme from Escherichia coli suggests that thioredoxin reductase exists in
      two conformations, both of which are necessary for catalysis [Waksman, G.,
      Krishna, T. S. R., Williams, C. H., Jr., & Kuriyan, J. (1994) J. Mol. Biol. 236,
      800-816]. These factors make it likely that the mechanism of this enzyme is
      complex. The rapid reaction of enzyme with nicotinamide adenine dinucleotide
      phosphate, reduced form (NADPH) (the reductive half-reaction), proceeds in three
      phases. The first phase represents the formation of an NADPH-FAD charge transfer
      complex. The second phase involves FAD reduction, with loss of the NADPH-FAD
      charge transfer band. The third phase shows a slower decrease in absorbance at
      456 nm and the formation of a reduced flavin-NADP+ charge transfer band. These
      and other results indicate that NADP+ and NADPH compete for the single binding
      site on oxidized and fully reduced enzyme and that NADP+ release does not limit
      the third phase of reduction. Experiments that include examination of the
      reductive half-reactions of active-site mutants, having the active-site disulfide
      removed by mutating one or both of the active-site cysteines, indicate that the
      third phase does not represent reduction by a second equivalent of NADPH.
      Comparison of the rate constants and temperature dependence of the reductive half
      reaction with those of turnover show that the reductive half-reaction is not
      solely rate-limiting in catalysis. The results suggest that wild type and each
      altered enzyme exists in a unique equilibrium of conformers. It is proposed that
      the third phase of the reductive half-reaction represents a flavin reduction
      event largely limited by the conformational change proposed in the structural
      work.

PMID- 9235992
TI  - Sequence context influencing cleavage activity of the K130E mutant of the
      restriction endonuclease EcoRI identified by a site selection assay.
AB  - We have generated several EcoRI mutants which exhibit a decreased cleavage rate
      on one of the five specific cleavage sites in bacteriophage lambda-DNA. To study
      the influence of the sequence context on the cleavage rate in more detail, we
      developed a site selection assay. From a complete set of 4096 plasmid substrates,
      differing in three bases on both sides of a recognition sequence, optimal (best
      cut) and unfavorable (worst cut) sequences were selected by repeated limited
      digestion, separation, and in vivo amplification of cleaved and uncleaved
      plasmids. In order to compare the sequence preferences of the inner arm mutant
      K130E and the wild type enzyme, the cleavage rates and sequences of individual
      plasmids from the resulting pools were determined. The inner arm mutant K130E
      selected pools with clearly defined consensus sequences and a high amount of
      palindromic sequences. The cleavage rates of the selected sequences are specific
      for the K130E mutant as is shown by their cleavage with other mutants. In
      contrast, wild type EcoRI does not lead to a selection in this assay. Pre-steady
      state kinetics show that preferences for a certain sequence context are a result
      of differences in the dissociation rates of the wild type enzyme. EcoRI is
      evolved to efficiently recognize and cleave each nonmethylated DNA invading the
      cell. Therefore, a fast dissociation after cleavage is not mandatory.

PMID- 9235993
TI  - Replication of M13 single-stranded viral DNA bearing single site-specific adducts
      by escherichia coli cell extracts: differential efficiency of translesion DNA
      synthesis for SOS-dependent and SOS-independent lesions.
AB  - In order to characterize mutagenic translesion DNA synthesis in UVM-induced
      Escherichia coli, we have developed a high-resolution DNA replication system
      based on E. coli cell extracts and M13 genomic DNA templates bearing mutagenic
      lesions. The assay is based on the conversion of M13 viral single-stranded DNA
      (ssDNA) bearing a single site-specific DNA lesion to the double-stranded
      replicative form (RF) DNA, and permits one to quantitatively measure the
      efficiency of translesion synthesis. Our data indicate that DNA replication is
      most strongly inhibited by an abasic site, a classic SOS-dependent noninstructive
      lesion. In contrast, the efficiency of translesion synthesis across SOS
      independent lesions such as O6-methylguanine and DNA uracil is around 90%, very
      close to the values obtained for control DNA templates. The efficiency of
      translesion synthesis across 3,N4-ethenocytosine and 1, N6-ethenoadenine is
      around 20%, a value that is similar to the in vivo efficiency deduced from the
      effect of the lesions on the survival of transfected M13 ssDNA. Neither DNA
      polymerase I nor polymerase II appears to be required for the observed
      translesion DNA synthesis because essentially similar results are obtained with
      extracts from polA- or polB-defective cells. The close parallels in the
      efficiency of translesion DNA synthesis in vitro and in vivo for the five site
      specific lesions included in this study suggest that the assay may be suitable
      for modeling mutagenesis in an accessible in vitro environment.

PMID- 9235994
TI  - Antisense inhibition of CAS, the human homologue of the yeast chromosome
      segregation gene CSE1, interferes with mitosis in HeLa cells.
AB  - We have analyzed the effects on HeLa cells of reduction of the CAS protein, the
      human homologue to yeast chromosome segregation protein CSE1. Expression of CAS
      antisense cDNA decreases the amount of CAS protein in HeLa cells and perturbs
      progression from G2 (retards transition from G2) to G1 in the cell cycle.
      Increased levels of cyclin B in CAS antisense transfected cells correlated with
      an arrest in G2 phase or mitosis. This arrest upon CAS attenuation is consistent
      with observations that yeast with CSE1 mutations are defective in mitosis and
      cyclin B degradation.

PMID- 9235995
TI  - HIV-1 genome dimerization: kissing-loop hairpin dictates whether nucleotides
      downstream of the 5' splice junction contribute to loose and tight dimerization
      of human immunodeficiency virus RNA.
AB  - The genome of all retroviruses consists of two identical RNAs noncovalently
      linked near their 5' end. Adjacent genomic RNAs from human immunodeficiency virus
      type 1 (HIV-1) can form loose or tight dimers depending on whether their
      respective kissing-loop hairpins (nts 248-270 in HIV-1Lai) bond via their
      autocomplementary sequences (ACS) or via the ACS and stem sequences [Laughrea,
      M., & Jette, L. (1996a) Biochemistry 35, 1589-1598]. Loose dimers from HIV-1Mal,
      but not HIV-1Lai, are stabilized by a sequence (3'DLS) located downstream of the
      5' splice junction [Laughrea, M., & Jette, L. (1996b) Biochemistry 35; 9366
      9374]. To understand the ACS-3'DLS interplay in the formation and stability of
      loose and tight HIV-1 RNA dimers, we replaced the ACS of HIV-1Lai (GCGCGC262) by
      GUGCAC, GUGCGC (two alternative HIV-1 ACS), or GAGCUC (a non-HIV ACS). For each
      mutant, RNAs truncated immediately upstream or downstream of the 3'DLS were
      prepared; their ability to dimerize and their thermal stabilities were compared.
      The results suggest that the ACS determines whether the 3'DLS participates in RNA
      dimerization: (1) GAGCUC262 led to poorly stable loose dimers due to the
      inability of the 3'DLS to stabilize them (the 3'DLS stabilized the GUGCAC and
      GUGCGC RNAs); (2) GAGCUC262 led to poor formation of tight dimers, due to an
      inhibitory effect of the 3'DLS (the 3'DLS had little effect on the tight
      dimerization of the GUGCAC, GUGCGC and GCGCGC RNAs). The results indicate that
      communication exists between HIV-1 RNA sequences respectively located upstream
      and downstream of the 5' splice junction; they are consistent with the idea that
      the 3'DLS plays two ACS-dependent roles in the dimerization process: loose dimer
      stabilization in HIV-1 RNAs bearing an HIV ACS (unless the ACS already conferred
      a thermostability equal or superior to that offered by the 3'DLS), and inhibition
      of tight dimer formation in an HIV-1 RNA bearing a non-HIV ACS.

PMID- 9235996
TI  - Roles for adenosine ribose hydroxyl groups in cyclic adenosine 5'-diphosphate
      ribose-mediated Ca2+ release.
AB  - Cyclic adenosine diphosphate ribose (cADPR) is a naturally occurring and potent
      Ca2+-mobilizing agent. Structural analogues are currently required as
      pharmacological tools for the investigation of this topical molecule, but
      modifications to date have concentrated primarily upon the purine ring. Two novel
      dehydroxylated analogues of cADPR have now been prepared from chemically
      synthesized nicotinamide adenine dinucleotide (NAD+) precursors modified in the
      ribose moiety linked to adenine. ADP-ribosyl cyclase of Aplysia californica
      catalyzed the conversion of 2'A-deoxy-NAD+ and 3'A-deoxy-NAD+ into the
      corresponding 2'A-deoxy-cADPR and 3'A-deoxy-cADPR analogues, respectively. These
      analogues were used to assess the effect of 2'- and 3'-hydroxyl group deletion in
      the adenosine ribose moiety of cADPR on the Ca2+-releasing potential of cADPR.
      These compounds were found to have comparatively markedly different activities as
      agonists for Ca2+ mobilization in sea urchin egg homogenate. 2'A-Deoxy-cADPR is
      similar to cADPR, whereas 3'A-deoxy-cADPR is at least 100-fold less potent,
      indicating that the 3'A-hydroxyl group, but not the 2'A-hydroxyl group, is
      essential for calcium releasing activity. EC50 values recorded were 32 nM, 58 nM,
      and 5 microM for cADPR, 2'A-deoxy-cADPR, and 3'A-deoxy-cADPR, respectively.
      Moreover, 200 nM 2'A-deoxy-cADPR was required to desensitize the cADPR-sensitive
      Ca2+ channel to a subsequent addition of 100 nM cADPR, but 20 microM 3'A-deoxy
      cADPR was required to produce the same desensitizing effect. This is in
      accordance with the 100-fold lower potency exhibited by the latter analogue. To
      further investigate the importance of the 3'-hydroxyl group, we have also
      synthesized 3'A-O-methyl-cADPR, in which the 3'-hydroxyl group of adenosine has
      been methylated and its ability potentially to donate a hydrogen atom in a
      hydrogen bond has been removed. Although inactive in releasing Ca2+, 3'A-O-methyl
      cADPR inhibited cADPR-induced Ca2+ release in a dose-dependent manner with an
      approximate IC50 value of 5 microM, whereas 3'-O-methyladenosine had no effect.
      This further supports the requirement of a 3'-OH group for Ca2+ releasing
      activity. In addition, however, it suggests that this group may not be crucial
      for ligand-receptor recognition. Thus, replacement of the hydrogen atom of the
      hydroxyl with a methyl group effects a change of activity from an agonist to an
      antagonist of cADPR-induced Ca2+ release. Two other analogues with modifications
      in the 2' and/or 3' positions, 3'-cADPR phosphate and 2',3'-cyclic-cADPR
      phosphate, were synthesized and tested for their Ca2+-mobilizing activity in sea
      urchin egg homogenates. Both analogues were inactive with respect to both
      agonistic and antagonistic activities on the cADPR-sensitive Ca2+ release
      mechanism. These are the first steps toward a wider structure-activity
      relationship for cADPR, and this is the first study to implicate a crucial role
      for the adenosine ribose hydroxyl groups of cADPR in the biological activity of
      this cyclic nucleotide. Additionally, this is the first report of a cADPR
      receptor antagonist that is not modified at the 8-position of the purine ring.

PMID- 9235997
TI  - The heptameric prepore of a staphylococcal alpha-hemolysin mutant in lipid
      bilayers imaged by atomic force microscopy.
AB  - We have used atomic force microscopy to study the oligomeric state of a
      genetically engineered mutant of staphylococcal alpha-hemolysin (alphaHL-H5) that
      can be arrested as a "prepore" assembly intermediate. AFM images of alphaHL-H5 on
      supported bilayers of a fluid-phase lipid, egg-yolk phosphatidylcholine (egg-PC),
      under conditions that lock alphaHL-H5 into the prepore state, clearly show a
      heptameric structure for many individual oligomers. The central dent of the
      prepore has a diameter of 3.2 +/- 0.2 nm. The distance between the centers of
      mass of neighboring subunits is 2.8 +/- 0.3 nm. The heptamer has an average
      diameter of 8.9 +/- 0.6 nm. These results support a recently proposed pathway for
      the assembly of alpha-hemolysin.

PMID- 9235998
TI  - G-protein-mediated signaling in cholesterol-enriched arterial smooth muscle
      cells. 1. Reduced membrane-associated G-protein content due to diminished
      isoprenylation of G-gamma subunits and p21ras.
AB  - Mechanisms contributing to altered heterotrimeric G-protein expression and
      subsequent signaling events during cholesterol accretion have been unexplored.
      The influence of cholesterol enrichment on G-protein expression was examined in
      cultured smooth muscle cells that resemble human atherosclerotic cells by
      exposure to cationized LDL (cLDL). cLDL, which increases cellular free and
      esterified cholesterol 2-fold and 10-fold, respectively, reduced the cell
      membrane content of Galphai-1, Galphai-2, Galphai-3, Gq/11, and Galphas. The
      following evidence supports the premise that the mechanism by which this occurs
      is due to reduced isoprenylation of the Ggamma-subunit. First, the inhibitory
      effect of cholesterol enrichment on the membrane content of Galphai subunits was
      found to be post-transcriptional, since the mRNA steady-state levels of Galphai(1
      3) were unchanged following cholesterol enrichment. Second, the membrane
      expression of alpha and beta subunits was mimicked by cholesterol and 17
      ketocholesterol, both of which inhibit HMG-CoA reductase. Third, inhibition of
      Galphai and Gbeta expression in cholesterol-enriched cells was overcome by
      mevalonate, the immediate product of HMG-CoA reductase. Fourth, pulse-chase
      experiments revealed that cholesterol enrichment did not reduce the degradation
      rate of membrane-associated Galphai subunits. Fifth, cholesterol enrichment also
      reduced membrane expression of Ggamma-5, Ggamma-7upper; these gamma subunits are
      responsible for trafficking of the heterotrimeric G-protein complex to the cell
      membrane as a result of HMG-CoA reductase-dependent post-translational lipid
      modification (geranylgeranylation) and subsequent membrane association.
      Cholesterol enrichment did not alter expression of G-gamma-5 mRNA, as assessed by
      reverse transcriptase polymerase chain reaction, supporting a post
      transcriptional defect in Ggamma subunit expression. Fifth, cholesterol
      enrichment also reduced the membrane content of p21ras (a low molecular weight G
      protein requiring farnesylation for membrane targeting) but did not alter the
      membrane content of the two proteins that do not require isoprenylation for
      membrane association&sbd;PDGF-receptor or p60-src. Reduced G-protein content in
      cholesterol-laden cells was reflected by reduced G-protein-mediated signaling
      events, including ATP-induced GTPase activity, thrombin-induced inhibition of
      cyclic AMP accumulation, and MAP kinase activity. Collectively, these results
      demonstrate that cholesterol enrichment reduces G-protein expression and
      signaling by inhibiting isoprenylation and subsequent membrane targeting. These
      results provide a molecular basis for altered G-protein-mediated cell signaling
      processes in cholesterol-enriched cells.

PMID- 9235999
TI  - G-protein-mediated signaling in cholesterol-enriched arterial smooth muscle
      cells. 2. Role of protein kinase C-delta in the regulation of eicosanoid
      production.
AB  - PGI2 generation by the vessel wall is an agonist for cyclic-AMP-dependent
      cholesteryl ester hydrolysis. The process of enhanced PGI2 synthesis is
      stimulated, in part, by G-protein-coupled receptor ligands. Cellular cholesterol
      enrichment has been hypothesized to alter G-protein-mediated PGI2 synthesis. In
      the studies reported herein, cells generated PGI2 in response to AlF4-,
      GTPgammaS, and ATP in a dose-dependent manner. G-protein agonists stimulated
      eicosanoid production principally by activating phospholipase A2, but not
      phospholipase C. This is in contrast to PDGF, which stimulated phospholipase A2
      and PLCgamma activities. Galphai subunits mediate G-protein agonist-induced PGI2
      synthesis, since ATP- and PDGF-induced PGI2 synthesis was inhibited by pertussis
      toxin. Although cholesterol enrichment reduced arachidonic acid- and PDGF-induced
      PGI2 synthesis, cholesterol enrichment enhanced PGI2 release in response to AlF4
      , GTPgammaS, and ATP. The enhancement of PGI2 release in cholesterol-enriched
      cells was augmented by mevalonate, which inhibits the ability of cholesterol
      enrichment to reduce membrane-associated G-protein subunits. Since cholesterol
      enrichment inhibited PDGF and AlF4--induced MAP kinase activity [Pomerantz, K.,
      Lander, H. M., Summers, B., Robishaw, J. D., Balcueva, E. A., & Hajjar, D. P.
      (1997) Biochemistry 36, 9523-9531] (the major mechanism by which phospholipase A2
      is activated), these results suggest that cholesterol enrichment induces other
      alternative signaling pathways leading to phospholipase A2 activation. A PKC
      dependent pathway is described herein that is involved in enhanced eicosanoid
      production in cholesterol-enriched cells. This conclusion is supported by two
      observations: (1) G-protein-linked PGI2 production is inhibited by calphostin,
      and (2) cholesterol enrichment augments the specific translocation of the delta
      isoform of PKC from the cytosol to the plasma membrane following treatment of
      cells with phorbol ester. These data support the concept that, in cells
      possessing normal levels of cholesterol, MAP-kinase-dependent pathways mediate
      eicosanoid synthesis in response to G-protein activation; however, under
      conditions of high cellular cholesterol levels, augmented G-protein-linked
      eicosanoid production results from enhanced PKCdelta activity.

PMID- 9236000
TI  - Self-assembly of designed antimicrobial peptides in solution and micelles.
AB  - Hydrophobic interactions are responsible for stabilizing leucine zippers in
      peptides containing heptad repeats. The effects of substituting leucine by
      phenylalanine and alanine by glycine on the self-assembly of coiled-coils were
      examined in minimalist antimicrobial peptides designed to form amphipathic alpha
      helices. The secondary structure of these peptides was monitored in solution and
      in diphosphocholine (DPC) micelles using circular dichroism spectroscopy. The
      leucine peptides (KLAKLAK)3 and (KLAKKLA)n (n = 3, 4) become alpha-helical with
      increasing concentrations of salt, peptide, and DPC. The aggregation state and
      equilibrium constant for self-association of the peptides were measured by
      sedimentation equilibrium. The glycine peptide (KLGKKLG)3 does not self
      associate. The leucine peptides and phenylalanine peptides (KFAKFAK)3 and
      (KFAKKFA)n (n = 3, 4) are in a monomer-tetramer equilibrium in solution, with the
      phenylalanine zippers being 2-4 kcal/mol less stable than the equivalent leucine
      zippers. Thermodynamic parameters for the association reaction were calculated
      from the temperature dependence of the association constants. Leucine zipper
      formation has DeltaCp = 0, whereas phenylalanine zipper formation has a small
      negative DeltaCp, presumably due to the removal of the larger surface area of
      phenylalanine from water. Self-association of the peptides is coupled to
      formation of a hydrophobic core as detected using 1-anilino-naphthalene-8
      sulfonate fluorescence. Carboxyfluorescein-labeled peptides were used to
      determine the aggregation state of (KLAKKLA)3 and (KLGKKLG)3 in DPC micelles.
      (KLAKKLA)3 forms dimers, and (KLGKKLG)3 is a monomer. Aggregation appears to
      correlate with the cytotoxicity of these peptides.

PMID- 9236001
TI  - The role of beta-sheet interactions in domain stability, folding, and target
      recognition reactions of calmodulin.
AB  - Single-residue mutations have been made of the hydrophobic Ile or Val residue in
      position 8 of each of the four calcium-binding loop sequences (sites I-IV) of
      Drosophila calmodulin. These highly conserved residues are part of the
      hydrophobic core of either calmodulin domain and are involved in the structural
      link of two calcium-binding sites via a short antiparallel beta-sheet. In the apo
      form, the replacement of Ile (or Val) by Gly causes a significant
      destabilization, shown by the unfolding of the secondary structure of the domain
      carrying the mutation. In the presence of calcium, the deficiency in alpha
      helical structure at 20 degrees C is restored for the mutants at site I, II, or
      III but not at site IV, which requires the further binding of a high-affinity
      target peptide to re-establish the native conformation. The extent of the
      destabilization is seen in the depression of the melting temperature of
      individual domains, which can be as large as 80 degrees C in the case of Ca4
      CaM(V136G). However, because of low values of the unfolding enthalpy for
      calmodulin domains, only relatively low values of <2 kcal/mol are implied for
      DeltaDeltaG, the free energy of destabilization due to mutation. Consistent with
      this, the secondary structure of any unfolded mutant domain is highly sensitive
      to solvent composition and is largely refolded in the presence of 12.5% (v/v)
      aqueous trifluoroethanol. Compared to wild-type calmodulin, the affinities of the
      mutants for calcium and target peptides from sk-MLCK at 20 degrees C are
      significantly reduced but the effects are relatively small. These results
      indicate that the conformation of calmodulin can be dramatically altered by
      mutation of a single highly conserved residue but that changes in solvent or the
      binding of a target sequence can readily compensate for this, restoring the wild
      type properties. The results also suggest that the integrity of both the apo- and
      holo-forms of calmodulin is important for the maintenance of its biological
      function and confirm the importance of conserving the structural function of the
      residues involved in the beta-sheet interactions.

PMID- 9236002
TI  - The P6-P2 region of serpins is critical for proteinase inhibition and complex
      stability.
AB  - Two of the prototypic serpins are alpha1-proteinase inhibitor and ovalbumin.
      alpha1-Proteinase inhibitor is a rapid inhibitor of a number of proteinases and
      undergoes the characteristic serpin conformational change on cleavage within the
      reactive center loop, whereas ovalbumin is noninhibitory and does not undergo the
      conformational change. To investigate if residues from P12 to P2 in the reactive
      center loop of ovalbumin are intrinsically incapable of being in an inhibitory
      serpin, we have made chimeric alpha1-proteinase inhibitor variants containing
      residues P12-P7, P6-P2, or P12-P2 of ovalbumin and determined their inhibitory
      properties with trypsin and human neutrophil elastase. With the P12-P7 and P6-P2
      variants, the steps before and after the fork of the branched suicide-substrate
      pathway were affected as reflected by changes in rates and stoichiometries of
      inhibition with both proteinases. The P12-P2 variant showed that those effects
      were nonadditive, with exclusive substrate behavior for elastase and only
      residual inhibitory activity against trypsin. The properties of the variants were
      consistent with them obeying the suicide-substrate mechanism characteristic of
      serpins. Enzyme activity was regenerated from complexes formed with the P6-P2
      variant faster than with wild-type indicating that the rate of turnover of the
      complex was increased. Based on proteinase susceptibility in the reactive center
      loops of the P6-P2 and P12-P2 variants, and on an increase in heat stability of
      the cleaved P12-P2 variant, it was concluded that the variants had undergone
      complete loop insertion on cleavage. These results show that the reactive center
      loop residues P12-P2 of ovalbumin can be present in inhibitory serpins although
      decreasing the inhibitory properties. These data also demonstrate that the
      residues in the P6-P2 region of serpins are critical for rapid inhibition of
      proteinases and formation of stable serpin-proteinase complexes.

PMID- 9236003
TI  - Repositioning the catalytic triad aspartic acid of haloalkane dehalogenase:
      effects on stability, kinetics, and structure.
AB  - Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an
      alkyl-enzyme intermediate. The covalent intermediate, which is formed by
      nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is
      activated by His289. The role of Asp260, which is the third member of the
      catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to
      asparagine resulted in a catalytically inactive D260N mutant, which demonstrates
      that the triad acid Asp260 is essential for dehalogenase activity. Furthermore,
      Asp260 has an important structural role, since the D260N enzyme accumulated
      mainly in inclusion bodies during expression, and neither substrate nor product
      could bind in the active-site cavity. Activity for brominated substrates was
      restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both
      double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold
      higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre
      steady-state kinetic analysis of the D260N+N148E double mutant showed that the
      decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon
      bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the
      alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster
      and via a different pathway than in the wild-type enzyme. Molecular modeling of
      the mutant showed that Glu148 indeed could take over the interaction with His289
      and that there was a change in charge distribution in the tunnel region that
      connects the active site with the solvent. On the basis of primary structure
      similarity between DhlA and other alpha/beta-hydrolase fold dehalogenases, we
      propose that a conserved acidic residue at the equivalent position of Asn148 in
      DhlA is the third catalytic triad residue in the latter enzymes.

PMID- 9236004
TI  - A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from
      Conus purpurascens venom.
AB  - A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from
      Conus purpurascens venom. Electrophysiological studies indicate that the peptide
      inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does
      not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist.
      Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than
      the acetylcholine-binding site. As ascertained by sequence analysis, mass
      spectrometry, and chemical synthesis, the peptide has the following covalent
      structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an
      amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the
      alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive
      inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+
      channel blockers).

PMID- 9236005
TI  - Restriction by ankyrin of band 3 rotational mobility in human erythrocyte
      membranes and reconstituted lipid vesicles.
AB  - Rotational diffusion of eosin-5-maleimide-labeled band 3 was measured in
      erythrocyte membranes at pH 9.4-10.4. Band 3 was found to be more mobile in this
      pH range than at pH 7.5. Similar results were obtained with spectrin-actin
      depleted membranes, where it was further shown that ankyrin is the only
      detectable protein released from the membrane at pH 10. Further experiments were
      performed at pH 7.5 to investigate the effects of rebinding purified ankyrin
      and/or band 4.1 to ghosts stripped of skeletal proteins. Ankyrin was found to
      reduce band 3 rotational mobility, but band 4.1 had no effect. A fluorescence
      binding assay revealed that fluorescein isothiocyanate-labeled ankyrin had
      similar binding parameters to those reported previously using 125I labeling.
      Finally, the rotational mobility of purified band 3 reconstituted into lipid
      bilayers was determined before and after ankyrin binding. The results of these
      reconstitution experiments were globally analyzed, assuming the existence of two
      populations of band 3 with different correlation times. The faster correlation
      time is consistent with that expected for either dimers or compact tetramers of
      band 3. Ankyrin binding reduces the proportion of band 3 contributing to the
      faster component. This result demonstrates that ankyrin promotes the association
      of band 3 into more slowly rotating complexes independently of any other
      components of the erythrocyte membrane. It has been reported that ankyrin
      contains two binding sites for band 3 [Michaely, P., & Bennett, V. (1995) J.
      Biol. Chem. 270, 22050-22057]. The results of the present study are thus
      explained by the ability of ankyrin to cross-link band 3 into larger diameter
      complexes. Cross-linking by ankyrin in part accounts for the slow components in
      the anisotropy decays of band 3 in the erythrocyte membrane. Other factors which
      probably influence band 3 aggregation include the membrane "fluidity" and protein
      concentration.

PMID- 9236006
TI  - Red cell membranes of ankyrin-deficient nb/nb mice lack band 3 tetramers but
      contain normal membrane skeletons.
AB  - The role of ankyrin in the formation and stabilization of the spectrin-based
      skeletal meshwork and of band 3 oligomers was studied by characterizing, in nb/nb
      mouse red cells, the effect of ankyrin deficiency on skeletal ultrastructure,
      band 3-skeleton associations, and band 3 oligomeric states. Despite severe
      ankyrin deficiency, nb/nb mouse red cell skeletal components formed a relatively
      uniform two-dimensional hexagonal array of junctional complexes cross-linked by
      spectrin tetramers. Treatment of nb/nb ghosts with the nonionic detergent C12E8
      (octaethylene glycol n-dodecyl monoether) resulted in nearly complete extraction
      of band 3. The extracted band 3 was present exclusively as band 3 dimers.
      Fluorescence photobleaching recovery and polarized fluorescence depletion
      measurements showed increases in the laterally (33% vs 10%) and rotationally (90%
      vs 76%) mobile fractions of band 3 in intact nb/nb compared to control red cells.
      The rotational correlation time of the major fraction of band 3 molecules was 10
      fold shorter in nb/nb compared to control red cells, indicating a significant
      relaxation of rotational constraints in nb/nb cells. These data suggest that,
      although ankyrin plays a major role in strengthening the attachment of the
      skeleton to the membrane bilayer, ankyrin is not required for the formation of a
      stable two-dimensional spectrin-based skeleton. The absence of band 3 tetramers
      in the membrane of ankyrin-deficient red cells suggests that ankyrin is required
      for the formation of stable band 3 tetramers.

PMID- 9236007
TI  - Differential effects of subunit interactions on protein kinase A- and C-mediated
      phosphorylation of L-type calcium channels.
AB  - We have expressed the pore-forming alpha1S (skeletal muscle isoform) and alpha1C
      (cardiac/brain isoform) subunits, as well as the accessory beta2a (cardiac/brain
      isoform) and alpha2/delta subunits of the L-type, dihydropyridine-sensitive
      calcium (Ca) channels in Spodoptera frugiperda insect cells (Sf9 cells) by
      infection with recombinant baculoviruses in order to facilitate biochemical
      studies of these rare, heteromultimeric membrane proteins. Since the L-type
      channels are believed to be regulated by protein phosphorylation, this expression
      system allowed us to investigate which subunits could act as substrates for
      protein kinase A and C (PKA and PKC) and to determine the potential role of
      subunit interactions in phosphorylation of the channel proteins. Using purified
      protein kinases in vitro, the membrane-associated alpha1S, alpha1C, and beta2a
      subunits were demonstrated to be phosphorylated stoichiometrically by PKA. The
      extent of phosphorylation of these subunits by PKA was similar whether the
      subunits were expressed alone or in combination. In addition, the alpha1C and
      beta2a subunits were phosphorylated stoichiometrically by PKC when expressed
      individually. In contrast, the alpha1S subunit, when expressed alone, was a poor
      substrate for PKC, despite the fact that this subunit has been shown to be an
      excellent substrate for PKC in native skeletal muscle membranes. Interestingly,
      co-expression of alpha1S with the beta2a subunit restored the ability of the
      alpha1S subunit to serve as a substrate for PKC. These results strongly suggests
      that subunit interactions play an important and potentially differential role in
      channel regulation by PKC, whereas phosphorylation of the same subunit by PKA
      occurs independent of subunit interaction. Furthermore, our results provide
      biochemical evidence that, when co-expressed, the alpha1C, alpha1S, and beta2a
      subunits of L-type Ca2+ channels are excellent substrates for PKA and PKC and
      support the hypothesis that phosphorylation of each of these subunits may
      participate in channel regulation by these kinases.

PMID- 9236008
TI  - Are there equilibrium intermediate states in the urea-induced unfolding of hen
      egg-white lysozyme?
AB  - Protein folding intermediates that are sometimes populated at equilibrium under
      mild denaturing conditions have attracted much attention as plausible models for
      the kinetic intermediates transiently populated in the refolding kinetic
      pathways. Hen egg-white lysozyme is often considered as a typical example of
      close adherence to the equilibrium, two-state unfolding mechanism. However,
      recent small-angle X-ray scattering studies suggest that an equilibrium
      intermediate state is significantly populated in the urea-induced unfolding of
      this protein at moderately acidic pH. In this work, we analyze the urea-induced
      unfolding of hen egg-white lysozyme on the basis of steady-state fluorescence
      measurements, characterization of the folding-unfolding kinetics, double-jump
      unfolding assays for the amount of native protein, and double-jump refolding
      assays for the amount of unfolded protein. Our results do not provide support for
      the presence of an intermediate state and, in particular, disfavor that the
      following two types of intermediates be significantly populated at equilibrium:
      (1) intermediates showing a substantial quenching of the tryptophan fluorescence
      (such as that observed in the transient intermediates found in the refolding
      kinetic pathway under strongly native conditions) and (2) associating
      intermediates. Also, the deconvolution of the radius of gyration unfolding
      profile by using the values for the amount of native state derived from our
      double-jump unfolding assays is consistent with a two-state unfolding equilibrium
      and suggests, furthermore, that, in this case, large alterations in the average
      structure of the unfolded ensemble do not take place in response to changes in
      urea concentration. This work points up possible pitfalls in the experimental
      detection of equilibrium folding intermediates and suggests procedures to
      circumvent them.

PMID- 9236009
TI  - The exchangeable yeast ribosomal acidic protein YP2beta shows characteristics of
      a partly folded state under physiological conditions.
AB  - The eukaryotic acidic ribosomal P proteins, contrary to the standard r-proteins
      which are rapidly degraded in the cytoplasm, are found forming a large
      cytoplasmic pool that exchanges with the ribosome-bound proteins during
      translation. The native structure of the P proteins in solution is therefore an
      essential determinant of the protein-protein interactions that take place in the
      exchange process. In this work, the structure of the ribosomal acidic protein
      YP2beta from Saccharomyces cerevisiae has been investigated by fluorescence
      spectroscopy, circular dichroism (CD), nuclear magnetic resonance (NMR), and
      sedimentation equilibrium techniques. We have established the fact that YP2beta
      bears a 22% alpha-helical secondary structure and a noncompact tertiary structure
      under physiological conditions (pH 7.0 and 25 degrees C); the hydrophobic core of
      the protein appears to be solvent-exposed, and very low cooperativity is observed
      for heat- or urea-induced denaturation. Moreover, the 1H-NMR spectra show a small
      signal dispersion, and virtually all the amide protons exchange with the solvent
      on a very short time scale, which is characteristic of an open structure. At low
      pH, YP2beta maintains its secondary structure content, but there is no evidence
      for tertiary structure. 2,2,2-Trifluoroethanol (TFE) induces a higher amount of
      alpha-helical structure but also disrupts any trace of the remaining tertiary
      fold. These results indicate that YP2beta may have a flexible structure in the
      cytoplasmic pool, with some of the characteristics of a "molten globule", and
      also point out the physiological relevance of such flexible protein states in
      processes other than protein folding.

PMID- 9236010
TI  - Starlings' preferences for predictable and unpredictable delays to food.
AB  - Risk-sensitive foraging theory is based on the premise that unpredictable runs of
      good or bad luck can cause a variable food source to differ in fitness value from
      a fixed food source yielding the same average rate of gain but no
      unpredictability. Thus, risk-sensitive predictions are dependent on the food
      intake from variable sources being not only variable but also unpredictable or
      'risky' in outcome. This study tested whether unpredictability is a component of
      the value that foraging starlings, Sturnus vulgarisattribute to food sources that
      are variable in the delay to obtain food. Two groups of birds chose between a
      fixed and a variable delay option; the variable option was unpredictable in the
      risky group and predictable in the risk-free group in the overall rate of intake
      it yielded. In both groups the fixed option was adjusted by titration to quantify
      the magnitude of preference for predictable and unpredictable variance. On
      negative energy budgets both groups were significantly risk-prone, with the risky
      group being significantly more risk-prone than the risk-free group. Switching the
      birds to positive budgets by doubling the size of each food reward had no
      significant effect on preference, and similar trends to those found with negative
      budgets were observed. These results are not readily explained by risk-sensitive
      foraging theory, but may be explained by the algorithm used by the birds to
      attribute value to average expected rewards.

PMID- 9236011
TI  - Group territoriality in two populations of African lions
AB  - Lionesses, Panthera leoin the Serengeti ecosystem, Tanzania, assess the odds of
      winning group-territorial contests by counting the number of opponents they hear
      roaring. They will approach intruders aggressively only if they outnumber them.
      Here the lionesses in the Serengeti are compared with another population living
      nearby but in strikingly different ecological circumstances. The lions of
      Ngorongoro Crater live at much higher densities owing to year-round availability
      of non-migratory prey species, but also suffer higher mortality from fighting.
      Playback experiments showed that lionesses in the crater differ from those in the
      Serengeti by approaching 'intruders' more quickly when the odds of winning are
      low. This increased aggression is interpreted in terms of the greater difficulty
      of holding a territory at high population density.

PMID- 9236013
TI  - Shoaling generates social learning of foraging information in guppies
AB  - Two experimental studies are reported which investigate the social learning of
      foraging information in guppies, Poecilia reticulataIn both cases, untrained
      adult female guppies swam with trained conspecifics to feed, and in the process
      learned a route to a food source. In experiment 1, subjects were given 5 days
      experience swimming with demonstrator fish trained to take one of two equivalent
      routes to food. When tested alone, subjects preferentially used the route of
      their demonstrators. Experiment 2 investigated whether this social learning could
      mediate the stable transmission of route preferences among small populations of
      fish. This experiment used a transmission chain design, in which fish in small
      founder populations were trained to take one of the two routes, with founder
      members gradually replaced by untrained conspecifics. Three days after all
      founder members had been removed, populations of untrained fish still maintained
      strong preferences for the routes of their founders. The results suggest that the
      tendency to shoal may facilitate a simple form of guided social learning, which
      allows guppies to learn about their local environments. They also imply that
      selectively neutral behavioural alternatives may be maintained as traditions in
      aggregated animal populations by very simple social mechanisms. The transmission
      chain method may be particularly useful for studying social species, such as the
      guppy, that do not respond well to isolation testing.

PMID- 9236012
TI  - Effects of experience on crab foraging in a mobile and a sedentary species
AB  - The effects of experience on prey and prey-patch choice were compared between two
      species of marine predatory crabs. The blue crab, Callinectes sapidus Rathbun, is
      highly mobile and forages in a variety of estuarine and lagoonal habitats. The
      Atlantic mud crab, Panopeus herbstii H. Milne-Edwards, is smaller and less mobile
      and is found mostly in oyster reefs and on shelly bottoms. In the laboratory,
      crabs were offered a choice between two prey types (juvenile hard clams,
      Mercenaria mercenaria Linne, and juvenile oysters, Crassostrea virginica Gmelin)
      following a preliminary phase in which crabs were trained to feed on clams only,
      oysters only or a mixture of the two prey types. In field enclosures, crabs were
      offered a choice between patches of juvenile hard clams located in an inter-tidal
      salt marsh and in an adjacent unvegetated inter-tidal flat after they were
      trained to feed in either one of the two habitat types. Both in the laboratory
      prey-choice and the field prey-patch choice experiments, blue crabs modified
      their foraging behaviour depending on previous experience. The effect of
      experience on their foraging behaviour did not diminish after 24 hours.
      Experience had no significant effects on the foraging behaviour of mud crabs.
      Differences in the ecological contexts (e.g. in the variability of prey quality
      and availability) in which the two species forage may explain the greater effect
      of experience on the blue crab foraging behaviour, although alternative
      explanations cannot be ruled out.

PMID- 9236014
TI  - Free food or earned food? A review and fuzzy model of contrafreeloading
AB  - Animals will work (e.g. lever press) for 'earned' food even though identical
      'free' food can easily be obtained from a nearby dish. This phenomenon, called
      contrafreeloading, appears to contradict a basic tenet of most learning,
      motivation and optimal foraging theories; namely that animals strive to maximize
      the ratio of reward, or benefit, to effort, or cost. This paper reviews the
      factors that have been found to affect the level of contrafreeloading, to try to
      explain the behaviour. In experiments involving intensive training,
      contrafreeloading may be explained on the basis of secondary reinforcement and/or
      differential exposure to the alternative food sources. However, contrafreeloading
      also occurs without prior training. Contrafreeloading declines with increasing
      hunger and with increases in the effort required to obtain the earned food: it
      also has an inverted-U relationship with the degree of stimulus change associated
      with the earned food. A fuzzy logic model is developed to predict the outcome of
      interactions between these factors. The model successfully simulates previous
      empirical findings and provides novel, testable predictions. It is argued that
      contrafreeloading does not contradict reinforcement theory, provided that the
      sensory reinforcement obtained from stimuli associated with the earned food is
      also taken into account. A functional explanation of why such stimuli are
      reinforcing, and of contrafreeloading itself, is based upon the advantage of
      gathering information for animals living in changing environments (i.e. an
      information primacy model). Animals work for earned food in order to update their
      estimate of a currently sub-optimal food source because, in the longer term, it
      may unpredictably become the optimal place to feed. Contrafreeloading is
      therefore a behaviour that, under natural conditions, is adaptive.

PMID- 9236015
TI  - Context-dependent fright reactions in captive European minnows: the importance of
      naturalness in laboratory experiments
AB  - The responses of ostariophysan fish to alarm substance (Schreckstoff) have been
      investigated extensively in the laboratory but there have been few tests of its
      role under natural conditions. Furthermore, existing studies of the efficacy of
      Schreckstoff as an alarm substance in the wild have typically employed indirect
      approaches and have failed to document specific behaviour in a quantitative
      manner. European minnows, Phoxinus phoxinuswere exposed to Schreckstoff in small
      aquaria. They responded with a suite of behavioural changes that are consistent
      with the explanation that they perceive danger. Fish from the same population
      were then exposed to Schreckstoff under conditions that more closely resembled
      their natural habitat. Under these near-natural conditions they showed a small
      decrease in feeding rate and a slight increase in group size, both effects being
      transitory and independent of stimulus concentration. These data reveal that the
      ostariophysan fright reaction is context-dependent and highlight the importance
      of quantifying the behaviour of fish exposed to Schreckstoff under fully natural
      conditions.

PMID- 9236016
TI  - Further evidence for visual landmark involvement in the pigeon's familiar area
      map
AB  - In previous experiments suggesting that previewing visual landscapes speeds
      homing from familiar release sites, restricted access to olfactory cues may have
      artefactually encouraged homing pigeons, Columba liviato resort to visual
      landmark orientation. Since evidence for the role of visual landmarks in wide
      ranging avian orientation is still equivocal, Braithwaite & Guilford's (1991,
      Proc. R. Soc. Lond. Ser. B245, 183-186) 'previewing' experiments were replicated:
      birds were allowed or denied visual access to a familiar site prior to release,
      but allowed ample access to olfactory cues. In experiment 1, allowing birds to
      preview familiar sites for 5 min prior to release enhanced homing speeds by about
      12%. In experiment 2, modified to reduce between-day effects on variation,
      previewing enhanced homing speeds by about 16%. These experiments support the
      conclusion that visual landmarks remote from sight of the loft are an important
      component of the familiar area map, although the nature of the landmarks and how
      they are encoded remain to be determined.

PMID- 9236017
TI  - Absence of odour learning in the stemborer parasitoid Cotesia flavipes
AB  - Parasitic wasps are commonly found to learn olfactory and visual cues that are
      associated with successful host location. For many parasitoids the cues that are
      associated with hosts vary in space and time, and are therefore unpredictable. An
      ability to learn allows the wasp to concentrate on those cues that will lead it
      to new hosts most effectively in a particular area. In contrast, parasitoids that
      forage in a predictable homogeneous environment and/or make only a few foraging
      decisions do not need to learn and should rely on innate responses to specific
      cues. The role of learning in host foraging was studied in Cotesia flavipes
      (Hymenoptera: Braconidae), a parasitoid of stemborer larvae with an ecology where
      learning is expected to be of low adaptive value. There was no evidence that C.
      flavipes uses odour learning in host-micro-habitat location. There was no
      significant effect of the development and emergence environment on the response
      level or preference towards the odour of infested plants. Neither was there
      evidence that experience with a particular plant-host complex during foraging
      influences subsequent foraging decisions in C. flavipes females. The absence of
      learning in C. flavipeswhich seems an exception among the parasitoids studied, is
      discussed in relation to its ecology.

PMID- 9236018
TI  - Experimental mate switching in pied flycatchers: male copulatory access and
      fertilization success
AB  - By making female birds pair successively with different males, and analysing the
      paternity of the eggs laid, it is possible to examine how a male's success in
      obtaining fertilizations is determined by the timing of his copulatory access to
      the female. Such an experiment is reported here with pied flycatchers, Ficedula
      hypoleucaMate switching was induced at different stages within the female's
      fertile period by removing the resident male. The paternity of the clutch was
      analysed by microsatellite DNA typing. Removed males had full paternity in the
      clutch if they were removed as late as after the second egg was laid (day 1), and
      they lost all paternity if they were removed more than 1 day before the first egg
      was fertilized (less than day -2). Male switching during the period day -2 to day
      1 always resulted in mixed paternity in the clutch. Males that were paired to the
      female for only a few (1-3) days during this period achieved on average more than
      one fertilization per access day, with a peak on day -1. Thus, assuming that the
      timing of observed pair bonds reflects the timing of each male's copulatory
      access to the female, the first eggs in the laying sequence were fertilized by
      inseminations occurring shortly before the time of fertilization, whereas the
      last eggs were fertilized by inseminations taking place several days prior to
      their fertilization. Our documentation of the most important period for
      copulatory access has some important implications for understanding sexual
      behaviour in this species.

PMID- 9236019
TI  - Variation in sperm precedence during mating in male flies, Dryomyza anilis
AB  - To understand how individual differences in fertilization success arises in the
      fly Dryomyza anilisvariation in sperm precedence between and within males was
      studied. In D. anilisa mating consists of a copulation followed by tapping
      sequences during which the male taps the external genitalia of the female. These
      tapping sequences increase last male sperm precedence. Each male in the
      experiment was repeatedly mated with a set of females. In the first treatment,
      mating was interrupted after the male had an intromission. In the second
      treatment, the male was allowed to perform five tapping sequences after an
      intromission. In the third treatment, the male was allowed to perform an
      unlimited number of tapping sequences after an intromission until interrupted by
      female resistance. There were large differences between males in all three
      treatments as shown by the 95% confidence limits of the mean fertilization
      success. Repeatabilities of mating time and the number of tapping movements per
      tapping sequence were high indicating clear differences between males in these
      components of mating behaviour. Within individual males, the more tappings per
      sequence, the higher the fertilization success. In matings with an unlimited
      number of tapping sequences, fertilization success depended on female resistance.
      Within-male variation in fertilization success was higher in matings with an
      unlimited number of tapping sequences than in matings interrupted after a
      copulation. Several components of male mating behaviour thus contribute to the
      variation in sperm precedence in D. anilisFemale behaviour, in particular,
      resistance of tapping movements, can also increase variation in sperm precedence.

PMID- 9236020
TI  - Odour and colour as cues for taste-avoidance learning in domestic chicks
AB  - In addition to being visually conspicuous, many chemically defended insects also
      produce olfactants when attacked. These olfactants may constitute 'warning
      odours', comparable in their effects to warning colours. This hypothesis was
      tested by examining the ability of two odours, almond and vanilla, to act as cues
      for avoidance of quinine-flavoured water in domestic chicks, Gallus gallus
      domesticusIn experiment 1, chicks were trained to avoid familiar-coloured quinine
      solution, novel-coloured solution, or novel-smelling solution. When the novel
      smell was almond it enhanced the rate of avoidance learning, as did the novel
      colour cue; but vanilla odour had no effect on rate of learning. In experiment 2,
      chicks were trained to avoid quinine solution that was paired with a compound cue
      involving both colour and odour. They were then tested in extinction with both
      cues, either cue alone, or neither cue. When the odour cue was almond it
      overshadowed the colour cue: chicks that had learned to avoid almond-smelling
      quinine solution of a particular colour subsequently avoided almond-smelling
      water and drank water that did not smell of almond, regardless of its colour.
      Vanilla odour, by contrast, exerted no control over behaviour when paired with a
      colour cue during acquisition. In experiment 3, chicks were trained to
      discriminate palatable from quinine-flavoured water when the latter was
      distinguished solely by an odour cue. The discrimination was learned more readily
      when the cue was almond than when it was vanilla; and a memory test revealed
      significant avoidance of almond odour, but not of vanilla, after 24 h. We
      conclude that odours can act as discriminative stimuli for taste-avoidance
      learning in birds and that they can sometimes exert more powerful control over
      behaviour than do visual cues. However, not all odours are equally efficacious.
      The results are discussed in relation to aposematism and mimicry.

PMID- 9236021
TI  - Determinants of the physiological colour patterns of juvenile parrotfish,
      Chlorurus sordidus
AB  - Field observations of the different physiological colour patterns (PCPs) of
      juvenile bullethead parrotfish, Chlorurus sordiduswere conducted at three sites
      around Lizard Island, Australia. The aim of the study was to quantify, using log
      linear analysis, the influence of simultaneously interacting variables upon the
      PCPs shown by this species in the field. It was proposed that features of an
      individual, such as body size (total length) and schooling behaviour
      (schooling/not schooling), as well as foraging activity (feeding/not feeding),
      were influential in PCP determination. In addition, the influence of time of day
      was considered. Overall, an individual's body size was the most significant
      factor, being over six times more important than foraging activity in determining
      the PCP displayed. The schooling behaviour of an individual was 40% more
      important than foraging activity in PCP determination. Furthermore, the
      correlation between body size and PCP was itself dependent on time of day whilst
      both foraging activity and schooling behaviour were independent of time of day.
      The systematic methodology used enabled interactions between variables to be
      ranked numerically and their biological significance to be discussed. The results
      present correlational evidence that PCPs may function for anti-predator purposes
      and provide the basis for future studies into the function of PCPs in juvenile C.
      sordidus

PMID- 9236022
TI  - Response of domestic chicks to methyl anthranilate odour
AB  - Methyl anthranilate is widely used to make ingestive stimuli taste aversive in
      studies of visually mediated passive-avoidance learning in domestic chicks,
      Gallus gallus domesticusHowever, since methyl anthranilate smells strongly to the
      human nose, its odour may be involved in the learning process. We sought (1) to
      determine whether chicks can use the odour of methyl anthranilate as a
      disciminative stimulus in passive-avoidance learning and (2) to evaluate the use
      of denatonium benzoate as an alternative odourless reinforcer. In experiments 1
      and 2, chicks were presented with familiar- or novel-coloured food or water, with
      or without the odour of methyl anthranilate or denatonium benzoate, to see
      whether either odour would elicit neophobia. Methyl anthranilate odour increased
      chicks' latency to eat or drink when it was presented in conjunction with novel
      coloured food or water, showing that chicks can detect it. Denatonium benzoate
      had no effect. In experiment 3, chicks learned to avoid food or water that was
      made unpalatable by means of denatonium benzoate and paired with the odour of
      methyl anthranilate, showing that chicks can use this odour as a discriminative
      stimulus in taste-avoidance learning. In experiment 4, chicks learned to avoid
      pecking at a pin-head coated with denatonium benzoate or paired with the odour of
      methyl anthranilate, showing that denatonium benzoate is a satisfactory
      reinforcer for one-trial passive avoidance learning and that the odour of methyl
      anthranilate is in itself a punishing stimulus. We conclude that methyl
      anthranilate odour does influence avian learning and that denatonium benzoate is
      a suitable odourless alternative for use as a punishing stimulus.

PMID- 9236023
TI  - Song transmission and auditory perception of distance in wood warblers
      (Parulinae)
AB  - The influence of breeding habitat on the evolution of song structure was examined
      in four wood warbler species of the sub-family Parulinae. The effects of song
      degradation on the ability of territorial paruline males to estimate distance by
      means of acoustic cues was also investigated. Song transmission characteristics
      of paruline breeding habitats were compared in southeastern Ontario, Canada;
      songs native to the habitat in which they were broadcast did not degrade less
      than foreign songs. The response of territorial paruline males to playback of
      'near' (undegraded) and 'far' (degraded) conspecific songs broadcast from the
      same position within the territory at the same amplitude were then compared.
      Males responded to near songs as they would to a conspecific territorial intruder
      and with less intensity to far songs, suggesting that males may use cues from
      song degradation to estimate distance to vocal conspecifics. Our results from
      transmission and playback experiments are discussed with respect to the ranging
      hypothesis, which proposes that selection should favour males that structure
      songs to minimize their degradation, so that songs function to disrupt or
      intimidate rivals by providing unreliable distance cues.

PMID- 9236024
TI  - Host responses to cowbirds near the nest: cues for recognition
AB  - Two cues (bill shape and vocalizations) that yellow warblers, Dendroica
      petechiamay use to recognize brown-headed cowbirds, Molothrus aterwere examined
      experimentally. Female yellow warblers responded more intensely to a control
      cowbird than one with a longer, thinner bill, which suggests that bill shape was
      an important cue in recognition. Responses involved close approaches, 'seet'
      alarm calls and sitting in the nest. Female yellow warblers distinguished between
      vocalizations of male and female cowbirds and those of a song sparrow, Melospiza
      melodia (control). They responded most intensely to female cowbird 'chatter
      calls' and least intensely to the sparrow song; responses to male cowbird
      'perched song' were intermediate in intensity. The results suggest that female
      yellow warblers recognize cowbirds on the basis of bill shape and vocalizations.
      Furthermore, these results, coupled with previous findings, suggest that female
      yellow warblers distinguish between male and female cowbirds by vocalizations but
      not appearance.

PMID- 9236025
TI  - Function and mechanism of mirror-image ambiguity in bumblebees
AB  - This study investigated the function and mechanism underlying a previously
      documented 'mirror-image ambiguity' (i.e. the mirror image of a pattern is
      treated as similar to the original stimulus) in foraging bumblebees, Bombus
      impatiensArtificial flowers were constructed so that the mirror image of a petal
      configuration was different from the left-right reversal of that configuration.
      Bees were first trained to discriminate between rewarding and unrewarding
      artificial flowers that differed only in their configuration of four differently
      patterned petals. On subsequent choice tests between two empty flowers, the bees
      chose the rewarding configuration (S+) over the unrewarding one (S-), over the
      mirror image and over the left-right reversal. In the critical test conditions,
      the bees failed to choose the mirror image over a novel petal configuration, but
      they chose the left-right reversal over the novel configuration (78% of the
      time). A mirror-image mental transformation was ruled out as a mechanism
      underlying mirror-image ambiguity. The notion that mirror-image ambiguity has
      general functional significance (e.g. is a by-product of the symmetry of the
      nervous system) received no support. The results favour a specific mechanism tied
      to a specific function: a left-right transposition of a floral pattern, which
      would enable foraging bees to recognize vertically symmetrical flowers that were
      partially occluded at the time of learning.

PMID- 9236026
TI  - Sex-related differences in habitat selection in wintering American kestrels,
      Falco sparverius
AB  - The American kestrel, Falco sparveriushas sex-related differences in habitat use
      during the non-breeding season, with females occupying more open habitats than
      males. Two competing hypotheses have been proposed to explain this phenomenon:
      (1) males and females prefer different habitats, and (2) males and females prefer
      similar habitats, but larger females exclude smaller males from preferred areas.
      This study experimentally investigated habitat selection in wintering kestrels by
      temporarily removing kestrels from areas, and then observing the numbers and sex
      of the kestrels that occupied vacated areas. The home ranges of 20 birds (10
      males and 10 females) were mapped and their occupants removed. Areas vacated in
      early winter (November 1994) were filled more quickly than those vacated in late
      winter (February 1995). Areas previously held by females were reoccupied more
      frequently than were those previously occupied by males. Female kestrels
      reoccupied vacated female areas more than vacated male areas. Male kestrels
      reoccupied vacated female and male areas equally. The results demonstrate that
      (1) high-quality kestrel habitat may be limited in the non-breeding season, (2)
      vacated areas are more likely to be reoccupied in the early winter than in late
      winter, (3) female kestrels appear at an advantage relative to males in occupying
      scarce and competed-for areas, and (4) male kestrels will use female areas when
      female occupants have been removed. It is hypothesized that open habitats are
      preferred over less open habitats because the former offer reduced risk of
      predation from bird-eating hawks.

PMID- 9236027
TI  - Effects of social and asocial learning on longevity of food-preference traditions
AB  - The influence of both social and asocial factors on the stability of a socially
      learned tradition of food preference was explored in colonies of domesticated
      Norway rats, Rattus norvegicusWe trained members of 'founding colonies' of rats
      to avoid eating a distinctively flavoured food and then introduced them into
      enclosures where they were offered a choice between the food they had learned to
      avoid and a familiar, safe food. We then monitored the food preferences of these
      colonies while we gradually replaced founding members with naive subjects.
      Traditions of food preference were more stable across generations of
      replacements: (1) in colonies that had food available 2 h/day than in colonies
      that had food available 24 h/day (experiment 1), (2) when replacement subjects
      each resided in their respective colonies for 2 days rather than for 4 days
      before themselves being replaced (experiments 2 and 3) and (3) when founding
      members of colonies had learned to avoid a relatively palatable diet (experiment
      4). The results of the first four experiments were consistent with the view that
      opportunities to learn asocially to eat a food other than that preferred by one's
      fellows reduced the stability of a food preference as it was transmitted across
      generations. We also found that introducing a naive individual into a tradition
      bearing colony reduced its rate of acquiring a food preference other than that of
      the colony it joined (experiment 5). The interactive effects of social and
      asocial learning on the stability of food preference traditions in Norway rats
      was discussed.

PMID- 9236028
TI  - Temporal aspects in the development of Belding's ground squirrels' litter-mate
      preferences
AB  - Four experiments were conducted to determine how experience around the time of
      natal emergence affected the development of litter-mate preferences in juvenile
      Belding's ground squirrels, Spermophilus beldingiSocial preferences were
      ascertained by observing six captive groups, each housed in outdoor enclosures
      beginning at natal emergence, and recording the frequency of dyadic play.
      Juveniles preferred their litter-mates as play partners on day 1 above-ground,
      demonstrating that pre-emergent interactions influenced social development.
      Whether cross-fostered young displayed play-partner preferences based on
      relatedness and rearing history depended on when young were exchanged with
      respect to natal emergence, which suggests that social development is especially
      sensitive to experience shortly before natal emergence. Juveniles do not display
      litter-mate preferences if they emerge into an environment from which dams have
      been removed, but in the present study, if juveniles interacted for 1 week before
      dams were withdrawn from enclosures, then litter-mate preferences were manifested
      both before and after dams were withdrawn. These results suggest that a
      foundation for litter-mate preferences is laid before natal emergence, and that
      preferences are solidified by interactions between litter-mates on their first
      few days above-ground. Finally, non-litter-mates that interacted with each other
      shortly after natal emergence were preferred social partners during later
      encounters compared with non-litter-mates denied the opportunity to interact
      shortly after emergence. Collectively, the four experiments demonstrate that
      social experience around the time of natal emergence is crucial to the
      developmental process that generates litter-mate preferences in S. beldingi1997
      The Association for the Study of Animal Behaviour

PMID- 9236029
TI  - Infant tufted capuchin monkeys' behaviour with novel foods: opportunism, not
      selectivity
AB  - To determine whether young capuchin monkeys, Cebus apellaselectively interacted
      with others concerning novel foods, 11 infants (4.5-12 months) living in two
      groups were observed following presentation of familiar or novel foods. Foods
      were presented either to the whole group or to infants in a section of the home
      cage to which only they had access. Infants showed more frequent interest in
      others' food and picked up foods more frequently when foods were novel, and they
      tended to eat novel foods more frequently than familiar foods. The pattern was
      the same whether the foods were presented to the group or only to infants.
      Infants expressed interest in others' novel foods equally often before and after
      sampling these foods themselves. The frequency of interest in others' food
      correlated positively with age. It is concluded that acceptance of novel foods in
      these monkeys occurs readily regardless of socially provided information about
      edibility. Social interactions do not appear to make important contributions to
      acceptance of novel foods by infant capuchin monkeys.

PMID- 9236030
TI  - Differential effects of mate competition and mate choice on eastern tiger
      salamanders
AB  - Male tiger salamanders, Ambystoma tigrinum tigrinumare slightly larger in body
      size and have considerably higher and longer tails than females. To determine how
      these dimorphic traits affected reproductive performance and success, we
      conducted breeding trials using 12 males and six females per trial and monitored
      male-female and male-male interactions. Larger males had an advantage in most
      aspects of mate competition investigated. Males with higher tails had no
      advantage in either mate competition or mate choice. Males with longer tails also
      had no advantage in mate competition but were preferred as mates by females.
      Larger males interrupted courting males more often than smaller males did. The
      form of male-male interference was conditional on body size and not on either
      tail dimension. If the intruder was larger than the courting male, it would shove
      the female away from the courting male and initiate courtship; if the intruder
      was smaller, it adopted a female mimicry tactic in which it positioned itself
      between the courting male and female and performed female behaviours to the
      courting male while simultaneously courting the female. Our trials indicated that
      the two components of sexual selection may influence the evolution of different
      male morphological traits in tiger salamanders. Mate competition may favour
      increased male body length; mate choice may select for greater male tail length.

PMID- 9236031
TI  - Does it pay to retrieve stored food items in sequence?
AB  - No Abstract

PMID- 9236032
TI  - Testing mutualism: a commentary on Clements & Stephens
AB  - No Abstract

PMID- 9236033
TI  - Reply to Roberts: cooperation is an outcome, not a mechanism
AB  - No Abstract

PMID- 9236034
TI  - Welcome to the Conference
AB  - No abstract

PMID- 9236035
TI  - Building Life-long Immunity: an Introduction to the Conference Theme
AB  - No abstract

PMID- 9236036
TI  - Research priorities in the field of vaccinology.

PMID- 9236037
TI  - Vaccination and public health.

PMID- 9236038
TI  - Industrial policy and its relevance to vaccines manufacturers.

PMID- 9236039
TI  - The Jennerian heritage: new generation vaccines for all the world's children and
      adults.

PMID- 9236040
TI  - Effect of age on outcome and epidemiology of infectious diseases.

PMID- 9236041
TI  - Policy making for vaccinations of adolescents/adults.

PMID- 9236042
TI  - Implementation of vaccination policies.
AB  - There are seven essentials for the implementation of vaccination policies. (1)
      Exact knowledge of the epidemiological situation allows us to decide how best to
      use vaccines for maximum benefit to the community as well as to the individual.
      (2) Active and dedicated research will ultimately solve scientific unknowns and
      lead to the development of ideal vaccines for infants, children, adolescents,
      adults and elderly persons. (3) Simple access depends on world-wide availability
      of high-quality vaccines, easy access to medical care, low costs, adequate
      reimbursement and clear liability. (4) An optimum delivery system of vaccines
      will be approached by reducing the number of necessary doses, introducing
      combination vaccines, using the oral route, increasing heat stability, avoiding
      misconception about contraindications and giving priority to vaccination in the
      first year of life. (5) Clear and open information campaigns by accepted
      vaccination authorities are urgently needed. (6) Since benefits of immunizations
      are invisible and because vaccines are not big money makers, financial and other
      supports of vaccination programs need constant pressure from the concerted action
      of professionals involved in immunization. (7) Continuous evaluation of national
      and international vaccination programs are crucial, followed by both reactions
      and actions.

PMID- 9236043
TI  - Recommendations for immunizations at adolescence in Europe.

PMID- 9236044
TI  - Implementation of adolescent vaccination programmes through school.

PMID- 9236045
TI  - Current developments in new vaccines for adolescents.
AB  - Routine immunization in early childhood is well accepted and healthcare policies
      are designed to achieve optimal immunization coverage in this age group. This
      machinery is so well designed that when new vaccines become available, they are
      included in infant immunization schedules, even if not necessarily needed at this
      age, just because we have no mechanism to get in touch, in a systematic way, with
      adolescents, adults, and the elderly. However, it is well recognized that
      adolescence is the age with the greatest risk for exposure to sexually
      transmitted infectious diseases. As several vaccines targeted at this age group
      are likely to become available in the near future, healthcare policies and
      vaccine combinations should be designed to provide an optimal vaccine coverage at
      this age. Implementing this vaccination policy would not only provide the most
      effective means of preventing infectious diseases, but it would also anchor
      adolescents into a chartered channel of comprehensive preventive health care.

PMID- 9236046
TI  - Immunity, components of the immune system and immune response.

PMID- 9236047
TI  - Rational design of antituberculosis vaccines: impact of antigen display and
      vaccine localization.

PMID- 9236048
TI  - Vaccine development against Helicobacter pylori infections.

PMID- 9236049
TI  - Epidemic diphtheria in the Newly Independent States of the former USSR--situation
      and lessons learned.

PMID- 9236050
TI  - Migration: public health issues (polio, hepatitis A, hepatitis B, tuberculosis,
      diphtheria).

PMID- 9236051
TI  - Adult pertussis: a salesman's dream--and an epidemiologist's nightmare.

PMID- 9236052
TI  - Booster policy for adults.
AB  - A little over 100 years ago the first vaccines were manufactured. Since this time
      of success no vaccines have been developed for the great scourges of our time
      i.e. Malaria, helminthic disease and HIV. The morbidity and mortality rates of
      pneumococcal infection, influenza, hepatitis B and lately diphtheria are high,
      while vaccination booster rates among adults are not of acceptable values. The
      following causes have been taken into consideration: (1) there is no acceptance
      of the necessity of vaccination (2) physicians themselves do not have
      sufficiently favourable attitudes towards vaccines to put a special emphasis on
      vaccination for their patients; (3) Quite often a period of 20-30 years will pass
      between the time of leaving school (at 18 years) and incidence of major illness
      (visit to a doctor), so that there is no medical counsel concerning prophylaxis
      for the adult population; (4) high-risk groups are clearly defined but few of
      them are properly advised and get proper medical attention. Suggested booster
      strategies are: (1) professional advisory service for population groups and
      special schooling for physicians; (2) development of a patient chip card
      containing information about vaccinations, booster intervals and person's history
      for every physician; and (3) development of new combined vaccines for adults such
      as influenza and pneumococcal vaccine alone or in combination with diphtheria and
      tetanus toxoid.

PMID- 9236053
TI  - Changes in the aging immune system.
AB  - The functional capacity of the immune system gradually declines with age. T
      lymphocytes are more severely affected than B cells or antigen-presenting cells.
      This is mainly due to the involution of the thymus which is almost complete at
      the age of 60. The host is then dependent on the T cell pool generated in earlier
      life. Continuous activation, clonal expansion and elimination of T cells of
      various specificities eventually leads to changes in the T cell repertoire.
      CD45RA+ "naive" cells are replaced by CD45RA- "memory" cells and a T cell
      receptor oligoclonality develops. At the same time, T cells with signal
      transduction defects accumulate. Age-related T cell alterations lead to a
      decreased clonal expansion and a reduced efficiency of T cell effector functions
      such as cytotoxicity or B cell help. Decreased antibody production and a
      shortened immunological memory are the consequence. Changes in the aging immune
      system represent a permissive factor for the frequent occurrence and the severity
      of disease. Efficient protection of elderly individuals by suitable vaccination
      strategies is therefore a matter of great importance.

PMID- 9236054
TI  - Development of an adjuvant to enhance the immune response to influenza vaccine in
      the elderly.
AB  - Elderly persons typically show diminished immune responsiveness to influenza
      vaccination. Chiron Vaccines has developed a novel oil-in-water adjuvant
      emulsion, MF59, to enhance vaccine immunogenicity without compromising safety and
      tolerability. MF59 was shown to augment influenza vaccine immunogenicity in
      senescent mice. Subsequently, eight similarly designed, randomized, controlled
      clinical trials of a subunit influenza vaccine combined with MF59 were conducted
      between 1992 and 1995 in 1807 elderly volunteers (> or = 65 years old). Mild,
      transient, injection-site reactions were increased with MF59, but systemic
      reactions generally were not. For two of the three vaccine antigens (B and
      A/H3N2), postimmunization haemagglutinin inhibition geometric mean titres were
      statistically significantly higher with MF59. During influenza season, fewer
      deaths occurred among MF59 recipients. This development programme demonstrates
      how an adjuvant that stimulates effectors associated with immunosenescence can
      improve the performance of an existing vaccine in elderly persons.

PMID- 9236055
TI  - Pneumococcal vaccination: four issues for western Europe.

PMID- 9236056
TI  - Influenza immunization.

PMID- 9236057
TI  - Live attenuated varicella vaccine for prevention of herpes zoster.

PMID- 9236058
TI  - Vaccination of the immunocompromised patient.
AB  - The increasing number of immunocompromised persons both in industrialized
      countries and the developing world are at higher risk of acquiring certain
      diseases. Health professionals and doctors need to implement adequate vaccination
      strategies. According to the type of the underlying disease, its course and the
      therapy, the response to vaccine may be suboptimal. Thus it is important to
      immunize when possible before treatment is initiated and to respect an adequate
      timing for the immunization after treatment or transplantation. Clear
      recommendations need to be provided to physicians. Household members and medical
      staff need to be adequately immunized in order to avoid additional risks of
      transmission to the immunocompromised patient. Finally, there is a need for more
      potent vaccines using new adjuvants or immunoregulators, new vaccines such as for
      meningitis B and combined vaccines with good immunogenicity in order to simplify
      immunization schedules and still provide longlasting protection.

PMID- 9236059
TI  - Good performance of vaccination by education.

PMID- 9236060
TI  - Public information and vaccination policy.

PMID- 9236062
TI  - Is preventive medical care worth the cost?
AB  - Preventive medical care is seen as a way to reduce medical costs because
      screening for diseases is likely to catch them earlier, thus making treatment
      less expensive. Such an argument does not take into account the costs associated
      with massive testing. Less expensive ways are described.

PMID- 9236061
TI  - Harmonization of vaccination policy.

PMID- 9236063
TI  - Concluding Remarks to the Conference on vaccinology: "Building Life-long
      Immunity"
AB  - No abstract

PMID- 9236076
TI  - Holes and grooves: the contribution of microscopy and taphonomy to the problem of
      art origins.
AB  - Optical and scanning electron microscopy, comparative anatomy, data from modern
      and Pleistocene carnivore accumulations, and analysis of archeological materials
      show that some of the pieces interpreted by various scholars as engraved or
      perforated bones from European Lower and Middle Paleolithic sites (such as Pech
      de l'Aze II, Stranska Skala, Kulna, Bois Roche and Cueva Morin) are not early
      manifestations of non-utilitarian behavior. Putative engravings are in fact
      vascular grooves, while perforated pieces are partially-digested bones
      regurgitated by hyenas. The current debate on art origins has often been centered
      on the symbolic value and cognitive implications of these and similar pieces
      without a first-hand analysis of the objects to provide convincing demonstration
      of the human origins of the marks. Such demonstration is a necessary prerequisite
      to any discussion of their significance for the evolution of symbolic behavior.

PMID- 9236077
TI  - Human remains from the Moravian Gravettian: the Dolni Vestonice 3 postcrania.
AB  - To add to our knowledge of European earlier Upper Paleolithic (especially
      Pavlovian) human biology, the postcranial skeleton of the Dolni Vestonic 3
      partial skeleton was excavated and reassembled. It represents the remains of an
      adult female, who was buried in a tightly flexed position with the ventral side
      down and turned slightly to the left. Subsequent compaction led to extensive
      damage to the axial skeleton and long bone epiphyses. It nonetheless retains the
      C1 and C2, fragments of the C5 to S3, portions of the pelvis, most of the long
      bone diaphyses, and a number of manual and pedal remains. Dolni Vestonice 3 was a
      relatively gracile individual in terms of diaphyseal robusticity and especially
      muscular attachment rugosity, despite the strong development of femoral and
      tibial diaphyseal structural buttresses. Upper limb asymmetry is slight and
      variable. She is similar to other earlier Upper Paleolithic remains in having
      warm temperate to tropical body proportions but is at the lower limit of
      Gravettian variation in body size indicators. There is no evidence of significant
      antemortem lesions on the preserved postcrania.

PMID- 9236078
TI  - A critical re-evaluation of the evidence for the presence of hominids in Lower
      Pleistocene times at Venta Micena, southern Spain.

PMID- 9236079
TI  - The Orce skull: anatomy of a mistake.

PMID- 9236083
TI  - OBITUARY: Rostislav Viktorovich Kazakov: 1941-1997
AB  - No abstract

PMID- 9236084
TI  - Temporal patterns in a fish assemblage of a semiarid mangrove zone in Madagascar
AB  - Gillnet sampling was conducted for a year in a tropical mangrove creek (SW
      Madagascar), characterized by a limited freshwater influence, a high turbidity
      and a tidal range up to 3 m. Sixty species of juvenile fishes were caught, 44
      species being of commercial interest. Catches were dominated by Gerreidae (27% of
      total abundance), Teraponidae (16%), Carangidae (13%) and Sparidae (12%). The
      temporary resident fishes in the mangrove zone represented 50% of the species and
      97% of the total abundance, the other species being rare (less than five
      individuals). The species richness, abundance and biomass per netting were low in
      the middle of the cool season (July-August). Monthly changes in the fish
      assemblage were particularly complex, with three species groups displaying a
      clear seasonal pattern, some species succeeding one another in a rather
      unstructured way, and three species abundant throughout the year. There was no
      clear structuring effect of temperature, salinity and turbidity on the fish
      assemblage. However, tidal, lunar and diel effects on the composition of the fish
      assemblage were evident. The species overlap between the Sarodrano mangrove fauna
      and the adjacent coral reef fauna is particularly weak with six species in common
      and shows that the mangrove plays only a very limited nursery role for coral reef
      species.

PMID- 9236085
TI  - Cortisol and glucose responses after acute stress by net handling in the sparid
      red porgy previously subjected to crowding stress
AB  - In red porgy Pagrus pagrus subjected to 3 weeks of chronic stress by crowding,
      plasma cortisol remained significantly higher in crowded fish compared to
      controls. There was no significant effect of crowding on plasma glucose levels.
      When the crowded fish were subjected to an acute handling the plasma cortisol
      response was similar to that of the uncrowded fish. No significant differences
      were found between the groups. The changes in plasma glucose following acute
      handling were also similar in both crowded and uncrowded fish.

PMID- 9236086
TI  - Genetic relationships among populations of wild resident, and wild and hatchery
      anadromous brook charr
AB  - To determine the genetic relationship of anadromous and resident life-history
      types within and among drainages, and compare several hatchery strains to their
      progenitor populations, brook charr Salvelinus fontinalis were examined for
      allozyme and mitochondrial DNA variation. Greater genetic similarity of sympatric
      anadromous and resident charr was found compared to similar life-history forms
      allopatrically, suggesting the two life-history types are not reproductively
      isolated. Low divergence among the mtDNA haplotypes suggests that the two life
      history types are members of the same evolutionary lineage. Population
      differentiation from mtDNA data exceeded that from estimates based on allozymes.
      Genetic deviations from expectations suggest that the hatchery strains were
      derived from few individuals. 1997 The Fisheries Society of the British Isles

PMID- 9236087
TI  - Nucleic acid contents and growth of first-feeding walleye pollock larvae in
      response to prey densities typical of sub-Arctic ecosystems
AB  - The growth, nucleic acid and protein contents of walleye pollock Theragra
      chalcogramma larvae reared at prey densities of 10, 30, 50, and 500 prey l-1 were
      measured for the first 9 days after the feeding initiation at 6&deg; C.
      Incremental growth rates of larvae (mm day-1) were low and variable for the first
      7 days after feeding initiation. Growth rates and rates of RNA, DNA, and protein
      accumulation by larvae reared at 500 prey l-1 were positive while those of larvae
      reared at the lower prey levels did not differ significantly from zero. The
      RNA/DNA ratio was variable and exhibited no significant trend among food
      treatments. Estimates of instantaneous protein growth rates ranged from 
      6&middot;7 to 13&middot;2% day-1 at food densities of 10 and 500 prey l-1,
      respectively, and were moderately correlated with larval RNA/DNA ratios
      (r=0&middot;628). The results suggest that in situ protein growth rates of first
      feeding pollock larvae may be influenced by prey fields within the range of
      ambient food densities reported for sub-Arctic ecosystems.

PMID- 9236088
TI  - Food and reproduction of Trichomycterus itacarambiensis, cave catfish from south
      eastern Brazil
AB  - Trichomycterus itacarambiensis is a troglobitic (cave-restricted) catfish found
      in the Olhos d'Agua Cave, Itacarambi Co., Minas Gerais, south-eastern Brazil. The
      cave is subject to a pronounced seasonality, and is flooded during part of the
      rainy season. The pigmentation degree is variable in T. itacarambiensis, a third
      of the population being true albinos; the eyes vary from normal to externally
      invisible. As expected for a cave-dwelling fish, T. itacarambiensis is a
      carnivorous generalist, which preys mainly on autochthonous insects and
      earthworms. It is a chemically oriented predator of bottom and surface animals,
      using foraging tactics also used by other cave catfishes, such as the pimelodids
      Pimelodella kronei and Imparfinis sp. However, bottom feeding seems to be more
      important for T. itacarambiensis than for the latter. There is a severe feeding
      stress during the dry season, when few individuals are able to get food.
      Reproduction is seasonal, with increased reproductive activity at the end of the
      rainy period, as recorded for Imparfinis sp., also a species living in a semi
      arid region with a well-defined dry season. It is estimated that up to 50% of the
      female T. itacarambiensis can reproduce every year, a high proportion for a
      troglobitic fish species. At least during the study period, pigmented individuals
      reproduced more frequently than the albinos.

PMID- 9236089
TI  - Habitat use by the fish assemblages of two chalk streams
AB  - Patterns of habitat use by fish assemblages in two chalk streams in southern
      England were examined to identify species preferences with respect to major
      habitat gradients. Both study sites, although differing in some physical habitat
      characteristics, mainly channel width, water temperature and instream cover,
      could be arranged similarly along a continuum extending from erosional to
      depositional habitats. Twelve fish species were collected from stream surveys
      conducted during July 1993. The habitat was partitioned into six fish species
      associations that could be assigned to three habitat guilds: depositional
      (Barbatula barbatula, Gasterosteus aculeatus and Anguilla anguilla), riffle
      (Leuciscus leuciscus, Thymallus thymallus and Salmo salar) and generalist (Salmo
      trutta, Phoxinus phoxinus, Gobio gobio, Cottus gobio, Lampetra planeri and
      Pleuronectes flesus). At low to moderate densities the different species
      associations were collected in the same habitat patch, but at higher densities
      there was a clear tendency to mutual avoidance. In particular, large trout
      appeared as strong interactors that tended to exclude other species from their
      territories. It is hypothesized that the fish assemblage of the Mill Stream and
      Bere Stream have partitioned the habitat in such a way as to minimize potential
      competition.

PMID- 9236090
TI  - Reproductive biology of the mosquitofish in a permanent natural lagoon in south
      west Spain: two tactics for one species
AB  - Introduced Gambusia holbrooki in a natural lagoon of southern Spain consisted of
      two age groups: 1992 cohort, 7-11 months old and 1993 cohort, <4 months old. In
      the 1992 cohort, females grew even during the gestation period at about 0.30 mm
      day-1. In the 1993 cohort, females displayed a high growth rate (0.55 mm day-1)
      and reached reproductive size in a few weeks, but stopped growing when they
      matured. All the 1992 cohort reproduced from mid-May to mid-June, but only 50% of
      the 1993 cohort reproduced, from mid-August to mid-September. Reproducing females
      were significantly larger in the 1992 cohort (39.8 mm) than in the 1993 one (34.8
      mm). The largest 1992 females cohort had reproduced previously; the 1993 cohort
      had not. The mean dry weight of intra-ovarian embryos decreased to a minimum
      immediately before birth. These metabolic costs represented 29.8 and 31.4% of the
      initial weights of the 1992 and 1993 embryos, respectively. Mean dry weight of
      full-term embryo was significantly higher in the 1992 cohort (0.80+/-0.129 mg;
      95% CL) than in the 1993 one (0.70+/-0.086 mg; 95% CL). With more females in
      1992, cohort fecundity was considerably higher (number of embryos=7151; 63%) than
      in the 1993 (4193; 37%) cohort. The population completed two generations each
      year (spring and summer). The spring stock grew slower than the summer one but
      continued to grow during the gestation period, reaching larger final lengths,
      with more synchronous reproduction and clearer evidence of a second reproductive
      event. Each reproductive stock displayed its own life-history characteristics,
      with significant differences between mean length of reproducing females, growth
      rate, mean brood size, offspring size, standard fecundity and minimum length at
      reproduction.

PMID- 9236091
TI  - The amount of food ingested in a single meal by rainbow trout offered chopped
      herring, dry and wet diets
AB  - Two-year-old 1&middot;5-kg rainbow trout were held in cages and conditioned by
      feeding either on low-fat chopped herring (H trout) or dry pellets (P trout) for
      15 weeks. Their satiation amounts were then determined under standard conditions.
      On a wet weight basis H trout ate 2&middot;5-3&middot;5 times more food than P
      trout; this was sufficient to compensate for the high water content of herring
      and thereby maintain the dry matter intake. When P trout were offered herring (PH
      trout) they consumed more food than when offered dry pellets but not as much as H
      trout. Stomach capacity restricted the intake and their dry matter intake was
      reduced by c. 40%. When H trout were offered dry pellets (HP trout) they adjusted
      their intake immediately close to the level of P trout although their larger
      stomachs could have accommodated more than twice this volume of dry food. The
      return of appetite after a satiation meal was almost linear with time. Appetite
      increased at c. 556 mg g-1 body weight h-1 for H trout and at 142 mg g-1 bw h-1
      for P trout. The return of appetite in PH trout was significantly slower (c. 370
      mg g-1 bw h-1) than in H trout; the previous dietary history of the PH trout
      limited their capacity to process larger volumes of wet food in a single meal.
      Fish offered dry diet (P and HP trout) had similar rates of appetite return
      despite their previous feeding history suggesting that the property of the dry
      feed itself might limit meal size. The total gastric emptying time of diets of
      similar dry matter content (with and without large amounts of water) was similar,
      but the delay time before gastric emptying starts tended to be longer for dry
      diets. Dry pellets appear to impose a demand for water that prolongs the gastric
      delay. This water demand is met partly by drinking since the trout fed on dry
      pellets drank significantly more (436&plusmn;189 mg kg-1 h-1) than unfed and
      herring-fed trout which drank little or not at all (65&plusmn;113 and
      70&plusmn;66 mg kg-1 h-1 respectively). Dietary water facilitated food processing
      and increased daily dry matter intake of trout when fed four times a day. When
      only one satiation meal per day was allowed, dietary water had no effect. It is
      concluded from this work that, in addition to gastric volume, a short-term
      limitation on the size of satiation meals in the rainbow trout is the
      availability of water to moisturize the food and thus to promote gastric
      digestion and emptying. 1997 The Fisheries Society of the British Isles

PMID- 9236092
TI  - Use of seasonally flooded marshes by fish in a Mediterranean wetland: timing and
      demographic consequences
AB  - In the Camargue (southern France), movements of fish between a canal and two
      seasonally flooded marshes were monitored continuously by fish traps for 3 years
      for one marsh and for 2 years for the other. The timing of the entry and exit of
      the main species was determined together with species annual demographic balance,
      defined as the difference between the number of fish leaving and the number of
      fish entering. Only some of the species inhabiting the canal colonized the
      marshes. Except those species that reproduced in salt or brackish waters, all the
      species colonizing the marshes reproduced in it. The most abundant of these
      species were small sized (mosquitofish, sand smelt and three-spined stickleback).
      The unpredictability of water levels in summer was particularly unfavourable for
      recruitment and survival of species that breed late in the year, e.g. pumpkinseed
      sunfish, or which prolonged their stay in the marsh and only attempted to leave
      just before the connection was broken, e.g. carp. Only the three-spined
      stickleback always had a positive demographic balance as a result of colonizing
      the marshes. Adults of this species entered in winter and young-of-the-year left
      in April. By limiting its stay in the seasonally flooded marshes, the stickleback
      minimized the risks related to environmental unpredictability. These results
      suggest that hydrology (temporal variations of water depth) may influence the
      fish community structure through interspecific differences in survival and
      recruitment, as a result of temporal variations in the use of seasonally flooded
      marshes.

PMID- 9236093
TI  - Ontogeny of the digestive tract during larval development of yellowtail flounder:
      a light microscopic and mucous histochemical study
AB  - The histological development and mucous histochemistry of the alimentary tract in
      larval yellowtail flounder were studied using light microscopy. Samples were
      taken when the larvae were first offered food at 3 days post-hatch, then at 7,
      10, 29, 36, and 46 days post-hatch, at which time they were metamorphosing.
      Regional partitioning of the digestive tract into the buccal cavity, pharynx,
      oesophagus, post-oesophageal swelling (PES), intestine, and rectum was complete
      by day 10. Goblet cells were present only in the buccal cavity, pharynx and
      intestine by day 7, but increased in number and distribution as development
      continued. By day 29, the posterior zone of the oesophagus had a marked increase
      in goblet cell density and mucosal folding. At the transition from oesophagus to
      PES/stomach stratified epithelium with goblet cells changed abruptly to a
      columnar epithelium with no goblet cells. Multicellular glands in the PES of 36
      day larvae allowed it to be defined as a stomach. The distinct brush border of
      columnar epithelium and the presence of goblet cells characterize the intestine
      and rectum. All goblet cells throughout the digestive tract were strongly
      positive for acid mucins as was the luminal layer of the stratified epithelia
      lining the buccal cavity, pharynx and oesophagus. The PES/stomach epithelium
      stained weakly for neutral mucins. No mucin staining was associated with the
      gastric glandular epithelium. The brush borders of the intestine and rectum were
      strongly positive for combinations of neutral and acid mucins.

PMID- 9236094
TI  - Calcium regulation in the freshwater-adapted mummichog
AB  - In light of recent findings of an unusual pattern of ionoregulation (high Na+
      uptake and negligible Cl- uptake) in the freshwater-adapted mummichog Fundulus
      heteroclitus, the pattern of Ca2+ regulation was examined. Under control
      conditions (water Ca2+=200 &mu;Eq l-1), unidirectional Ca2+ influx was
      11&plusmn;4 nEq g-1 h-1. Acute variation of external Ca2+ levels revealed a
      saturable Ca2+ uptake system with a relatively high affinity (Km=125&plusmn;36
      &mu;Eq l-1) and a transport capacity (Jmax=31&plusmn;4 nEq g-1 h-1) comparable to
      those of other teleosts. Lanthanum (equimolar to [Ca2+]) significantly blocked
      Ca2+ uptake by 67% whereas mag-nesium had no effect. Chronic low Ca2+ exposure
      (50 &mu;Eq l-1) stimulated Ca2+ uptake almost three-fold above control values,
      whereas chronic high Ca2+ exposure (20 000 &mu;Eq l-1) had no effect. Lanthanum
      and chronic low Ca2+ treatments disturbed the normally positive Ca2+ and Na+
      balances of the animals whereas acid-base balance and ammonia excretion were
      undisturbed. The results indicate that Ca2+ regulation by the mummichog conforms
      to the model for freshwater Ca2+ transport whereby chloride cells on the gills
      take up Ca2+ actively from the water. However, the absence of extra-intestinal Cl
      uptake and the recent demonstration of significant Ca2+ uptake by opercular
      epithelia raise questions about the relative roles of branchial and opercular
      epithelial chloride cells in freshwater F. heteroclitus. 1997 The Fisheries
      Society of the British Isles

PMID- 9236095
TI  - Interannual variation in condition of the mackerel icefish
AB  - Mackerel icefish Champsocephalus gunnari are widespread on the South Georgia
      (54&deg; S, 36&deg; W) shelf. Analysis of condition indicated a strong
      interannual variation. High condition indices, indicative of good feeding
      conditions, were present when krill were abundant in the region. Years when krill
      were scarce and condition index was consequently low, were consistent with years
      when indices from land-based krill predators also indicated that krill were
      scarce.

PMID- 9236096
TI  - Genetic divergence at the NAD+-dependent malic enzyme locus in Atlantic salmon
      from Europe and North America
AB  - The distribution of genetic variation for NAD+ malic enzyme (ME*) polymorphism in
      the Atlantic salmon was assessed in both anadromous and resident populations. The
      analysis revealed a major allelic divergence between North America and Europe.
      The *80 variant occurred in 39 of 40 North American samples, ranging in frequency
      from 0 to 0&middot;515. In contrast, it was detected in only three fish from two
      of the 35 European locations analysed. Eleven fish from two rivers in north-west
      France had the *110 variant. While heterogeneity among North American populations
      was significant, no regional differentiation was apparent and anadromous and
      resident salmon were not found to differ.

PMID- 9236097
TI  - Reproductive cycling and fecundity estimation in the upland bully
AB  - The upland bully is a prolific and widespread member of New Zealand freshwater
      fish communities that may mature at age 1 (or earlier). It begins spawning in
      spring, laying as many as eight clutches of eggs over the spring and summer, at
      periods as brief as 13 days. Ovaries contain two modes of maturing oocytes, so
      that oogenesis must be continual during the spawning season. This poses
      difficulties in fecundity estimation, which were solved by captive rearing. The
      ovoid eggs are about 2 mm long; egg size declines with clutch number during the
      summer, but increases with fish size. Clutch size varied, in 70 spawnings, from
      121 to 880 eggs, with total seasonal fecundity up to >5000 eggs. The production
      of multiple clutches greatly increases seasonal fecundity and may explain the
      success of this species in sometimes unreliable or harsh environments.

PMID- 9236098
TI  - First events in lipid absorption during post-embryonic development of the
      anterior intestine in gilt-head sea bream
AB  - Structural development and lipid absorption in anterior intestine of gilt-head
      sea bream Sparus aurata, were studied by light and electron microscopy during
      three stages of post-embryonic development: (1) the endotrophic period from
      hatching day (day 0) to mouth opening day (day 3); (2) the endo-exotrophic period
      from days 3 to 15; (3) the exotrophic period after day 15. During the 2 days
      following hatching, there was no trace of lipids in intestinal epithelia. Before
      mouth opening day, the first lipoproteic particles of endogenous origin appeared
      in entero-cyte endoplasmic reticulum and Golgi apparatus. During the endo
      exotrophic period, lipoproteinogenesis increased weakly until day 9, and more
      greatly between days 9 and 15. It intensified at the beginning of the exotrophic
      period to remain at a high level afterwards. Until day 15, few transfers of
      lipoproteins to interenterocyte spaces occurred, whereas no lipoproteins were
      detectable in the blood flow from days 7 to 9. Their concentration increased
      slightly between days 9 and 15 to become intense afterwards. Lipid droplets
      appeared from day 7, and subsisted until the end of endo-exotrophic period.
      Possible relationships between very low density lipoproteins and chylomicron type
      lipoproteins and lipid droplets related to lipid excess in food are discussed.

PMID- 9236099
TI  - Cloning and characterization of pejerrey mitochondrial DNA and its application
      for RFLP analysis
AB  - Probes were cloned, characterized, and developed for all regions of the
      mitochondrial DNA (mtDNA) of pejerrey Odontesthes bonariensis to provide the
      basis for the study of genetic diversity of South American atherinopsinii and to
      enable species identification from small amounts of tissue. The mtDNA was
      extracted from liver and cleaved with Eco RI, producing four fragments
      (7&middot;4, 3&middot;4, 3&middot;1 and 2&middot;9 kb) which were cloned using
      pUC118 plasmid vectors. Sequence analysis from both ends of the fragments showed
      that they encode tRNA (Asp, Phe, and Ser-TGA), 12 S rRNA, cytochrome oxidase (CO)
      II, NADH 4, 5, and 6, and the d-loop, and that the relative positions of these
      genes are identical to those in the mtDNA of other teleosts. A comparison of
      homology with carp mtDNA nucleotide sequences revealed that tRNA (Phe and Ser
      TGA) and CO II were relatively conserved, whereas the d-loop region was highly
      divergent. The cloned mtDNA probes detected mtDNA fragments from about 800 ng of
      total DNA extracted from liver, muscle, and single embryos of O. bonariensis, and
      were effective for restriction length fragment polymorphism (RFLP) analysis of
      Patagonina hatcheri, the most distant atherinopsine relative of pejerrey. The
      cloned mtDNA probes may be useful for the analysis of genetic diversity and non
      destructive species identification, including the examin-ation of eggs, larvae
      and juveniles. The mtDNA sequences reported here provide the basis for the design
      of primers for PCR-based RFLP analysis. 1997 The Fisheries Society of the British
      Isles

PMID- 9236100
TI  - Mitochondrial DNA differentiation among East and West African Nile tilapia
      populations
AB  - Variation of the ND5/6 mtDNA fragment was studied in six Nile tilapia populations
      using PCR and RFLP analysis. The observed variation allows a strict
      discrimination between eastern and western African populations.

PMID- 9236101
TI  - Identification of Anguilla japonica and A. marmorata elvers by allozyme
      electrophoresis
AB  - In Taiwanese waters, the morphologically similar elvers of Anguilla japonica and
      A. marmorata can be distinguished easily at the following loci examined: CK-D*,
      LDH-B*, sMDH-A* and sMDH-B*. Among these, CK-D* and LDH-B* have fixed allelic
      differences which can be used as a synoptic key for easy discrimination of the
      elvers of these two species.

PMID- 9236102
TI  - Egg survival and timing of hatch in two Scottish Atlantic salmon stocks
AB  - Atlantic salmon eggs from the Rivers Oykel and Shin were monitored in three
      rivers and in culture. Significant mortality, attributable to low pH, was found
      for both stocks in the River Oykel though it was eightfold higher for the non
      native Shin eggs. Shin eggs hatched earlier at all three wild sites but hatched
      later in culture. The observations are consistent with genotype-environment
      interactions for pH sensitivity and developmental rate.

PMID- 9236103
TI  - Opsin sequences of the rod visual pigments in two species of Poeciliid fish
AB  - The rod opsin sequences from Gambusia affinis holbrooki and Poecilia reticulata
      were cloned and sequenced. The opsin sequences were found to be 96&middot;8%
      identical, reflecting the similarity of the rod visual pigment absorbances in
      these two Poeciliid fish.

PMID- 9236104
TI  - The emergence of genetic coding in physical systems.
AB  - A simple model of molecular biological translation, based on the classification
      of polymers as either information carriers or functional catalysts, is used to
      analyse formal constraints on physical systems which utilise genetic coding. We
      investigate (i) how the structure-function relationship for coding assignment
      catalysts constrains the selection of genetic information which can sustain
      functional self-organisation and (ii) what general prerequisites must be
      satisfied for selection to give rise to an increase in functional complexity.
      This is done by considering two separate alphabets and defining the complete set
      of assignments from letters of one alphabet onto letters from the other. A code
      is defined as a set of assignments which maps each letter from the first alphabet
      onto a letter from the second alphabet. We enumerate all the embeddings of the
      assignment functions in the minimal sequence space of strings of letters from the
      second alphabet and demonstrate how the embeddings can be classified according to
      whether they allow different codes to be represented unambiguously in the minimal
      sequence space of strings of letters from the first alphabet. Non-minimal
      embeddings are also discussed. Finally, we consider how the mutual specification
      of letters of the two alphabets and assignment functions can be decomposed into
      more highly differentiated classes. Only a certain class of embeddings allows
      coding to be preserved under decomposition. We conclude that the evolution of
      increasing coding complexity can take place only when special conditions are
      satisfied regarding the structure-function relationship for the coding assignment
      catalysts.

PMID- 9236105
TI  - Seven helix receptors are enzymes catalysing G protein activation. What is the
      agonist Kact?
AB  - We analysed a model assuming that the G protein activation process is an enzyme
      catalysed reaction: (i) GGDP recognition, (ii) GDP release, (iii) GTP binding and
      (iv) activated GGTP (or betagamma followed by alphaGTP) release. This model
      suggests (1) that the agonists Kact value may decrease with increasing G protein
      expression. At low G protein concentrations, the agonists Kact value reflects
      binding to the 'low affinity state'. If the G protein concentration is
      saturating, the agonists Kact values are correlated but not identical to their KD
      values for the 'high affinity state' observed in binding studies. (2) All the G
      proteins recognized by a receptor behave as competitive antagonists with respect
      to each other. (3) Overexpression of G proteins which recognize only the active
      receptor state may result in constitutive receptor activation. The rate of G
      protein activation can be accelerated by facilitating G protein recognition, by
      increasing the rate of GDP release, or by activating G protein release. Our model
      explains why guanyl nucleotides are essential for G proteins activation yet
      inhibit agonist binding, and why the ability of receptor ligands to simulate G
      protein activation is not always correlated with their ability to distinguish two
      receptor states, at equilibrium. It can also explain the inhibitory effects of
      GDP and of the G protein betagamma subunit.

PMID- 9236106
TI  - Evolutionary advantages of cell specialization: save and protect DNA.
AB  - As the transcribed regions of nuclear DNA are in a more open state, they are
      liable to be damaged by naturally or environmentally produced mutagens. Cell
      specializations make it possible to express fewer genes in individual cells of
      multicellular organisms, thus protecting genes from the damage of mutagens. We
      propose that this might account for the advantage of cell specialization, as an
      alternative to the traditional conception that cell specializations result in
      increased efficiency. The most efficient cell specialization to protect DNA is in
      the segregation of germ cell(s) and somatic cell(s). But in optimal environments,
      such specialization is expected to reduce the rate of reproduction, which might
      counteract its advantage of protecting DNA.

PMID- 9236107
TI  - Re-assessing the virological approach to HIV pathogenesis: can it explain AIDS as
      an immunological disease?
AB  - Over 10 years after the discovery of HIV, its molecular virology still fails to
      explain the clinical immunology of AIDS. The prevailing paradigm of AIDS
      pathogenesis, called here the "virological hypothesis", argues that viral
      attributes such as cytopathicity, replicability, syncytiality, cell tropism,
      emergent virulence, and viral load explain why infection develops to a life
      threatening immunodeficiency. However, these attributes-singly and in combination
      are shown here to be inadequate to explain the latency, immunological damage, and
      clinical dynamics of the disease of AIDS. The virological paradigm cannot explain
      the disease-free period (clinical latency); the mechanism and dynamics of CD4 T
      cell loss; the reason for the onset of disease at a given time-point; the
      relationship of CD4 T cell loss to AIDS-type disease; nor the idiosyncratic
      constellation of immunological and clinical phenomena that comprise AIDS as a
      unique syndrome. HIV as it is currently understood does not have the virological
      characteristics necessary to create a disease such as AIDS through direct
      classical (i.e. cytopathic) mechanisms. It is clear that the pathogenesis of AIDS
      remains unknown. Therefore, treatment based solely on inhibiting viral mechanisms
      as with antivirals-is very likely to be insufficient. In addition, the molecular
      epidemiology of pathogenesis has been very poor; there is an enormous amount that
      is not known about the clinical immunology of AIDS, and the central question
      remains of how CD4 cell loss relates to clinical immunodeficiency. The conclusion
      drawn is that the virology of HIV has been pursed at the cost of understanding
      AIDS itself; that an emphasis on AIDS as an immunological disease is long
      overdue; and that appropriate treatment of AIDS will not be possible until the
      clinical immunology of AIDS is understood.

PMID- 9236110
TI  - Globin introns: ancient or modern?
AB  - Some globin introns appear to be ancestral features, others have been interpreted
      as later additions. However, these "anomalous" introns may be ancient relics of
      internal duplications within the original gene.

PMID- 9236112
TI  - Community structure and the interplay between interspecific infection and
      competition.
AB  - Our motivation is the need to understand how two different interactions between
      species-shared infection and interspecific competition-combine to determine
      community structure. We introduce a proto-typical model of two hosts sharing a
      pathogen and also competing directly. We discuss forces of infection, forces of
      competition and invasion criteria and their relevance to long-term outcomes and
      community structure. To understand their interplay, we consider first purely
      competitive and second purely infective interactions. We then investigate our
      full model to establish how the two forces combine and how the combination and
      related invasion criteria determine community structure. The forces of infection
      and competition do not merely add; there is a synergetic resistance to invasion.
      Using generalised invasion criteria and subsidiary conditions for the feasibility
      and stability of uninfected coexistence, we classify long-term outcomes. We
      distinguish two main routes to three-species coexistence. In the first, two host
      species, each of which would not alone support the pathogen, support it jointly
      if interspecific competition is relatively weak, interspecific infection strong.
      In the second, at least one host species would alone support the pathogen and
      both are invadable by the other, but subsidiary conditions yield two cases. In
      one, infected coexistence results when the two hosts would coexist stably purely
      competitively and at sufficiently high densities to support the pathogen jointly.
      Thus coexistence is promoted by weak interspecific competition but there is a
      tension between weak interspecific infection favouring invadability and strong
      interspecific infection promoting pathogen survival. In the other, infected
      coexistence results when the two hosts would not coexist in the absence of the
      pathogen. This pathogen-mediated host coexistence is expected where there is
      strong intraspecific infection (lowering densities) and weak interspecific
      infection (favouring invadibility) as necessary. Results are compared with
      previous work and apparent competition and resource- and transmission-mediated
      coexistence are discussed.

PMID- 9236113
TI  - Effect of time delay and evolutionarily stable strategy.
AB  - In this paper, a simple two-phenotype model with time delay is investigated. The
      main results are that: (i) the stability of the interior equilibrium point of the
      pure strategy model not only depends on the property of the payoff matrix but
      also the effect of time delay; (ii) the conditions of the evolutionarily stable
      strategy in the two-phenotype model with time delay are completely identical with
      the conditions in the two-phenotype model with no time delay; and (iii) a mixed
      evolutionarily stable strategy can be an unstable equilibrium state of the
      population in the two-phenotype model with time delay.

PMID- 9236114
TI  - A numerical study of the critical line of Kauffman networks.
AB  - Kauffman networks were introduced in 1969 as a model of genetic regulatory
      systems. One of the most striking successes of this model is its ability to
      reproduce, for a critical value of its parameters, the observed scaling laws of
      the average cell replication time and of the average number of cell types in a
      given organism vs. the number of genes. Yet, the numerical evidence for such
      scaling laws in the model is still unsatisfactory, and restricted to a particular
      critical point, while we expect that the scaling behaviour is universal along the
      critical line. In this paper we try to sharpen the evidence for the scaling
      behaviour of critical systems, carrying on a detailed numerical investigation of
      their properties. We measure the length of the cycles (which in the model
      represents the period of cell cycles) and their number (which represents the
      number of cell types) for a point of the critical line different from the only
      one previously studied. Our results seem to confirm that such quantities scale as
      radicalN for all critical systems, at least for lengths and numbers small enough.
      On the other hand, we found that their probability distributions are very broad
      (power-law like) and become broader with system size. This means that there is an
      effective scale of the length and of the number of cycles that increases much
      faster than radicalN, and in the infinite size limit the biological analogy found
      by Kauffman may be lost. A numerical study of the modular structure of critical
      networks supports this conclusion. The implications of this fact for the
      biological interpretation of the model are briefly discussed. Finally, we found
      that the typical weight of the attraction basins tends to zero as a power law in
      the infinite size limit, with an exponent which seems to be universal along the
      whole critical line.

PMID- 9236115
TI  - The necessity of cofactors in the pathogenesis of AIDS: a mathematical model.
AB  - Current arguments for the role of cofactors in the initiation of a chronic HIV
      infection and progression of AIDS are given. The natural history of an HIV
      infection as affected by cofactors which provide additional stimulatory signals
      is explored through a mathematical model. The model demonstrates that "antigen
      load" plays a role in determining susceptibility to an HIV infection. It also
      suggests that certain individuals may not be able to be infected by small doses
      of HIV and that the identification and treatment of existing cofactors may be
      useful in treating early stages of HIV infection. Prevention of cofactor
      exposures may also protect against HIV infection.

PMID- 9236116
TI  - Transcriptional activation via DNA-looping: visualization of intermediates in the
      activation pathway of E. coli RNA polymerase x sigma 54 holoenzyme by scanning
      force microscopy.
AB  - Scanning force microscopy (SFM) has been used to study transcriptional activation
      of Escherichia coli RNA polymerase x sigma 54 (RNAP x sigma 54) at the glnA
      promoter by the constitutive mutant NtrC(D54E,S160F) of the NtrC Protein
      (nitrogen regulatory protein C). DNA-protein complexes were deposited on mica and
      images were recorded in air. The DNA template was a 726 bp linear fragment with
      two NtrC binding sites located at the end and about 460 bp away from the RNAP x
      sigma 54 glnA promoter. By choosing appropriate conditions the structure of
      various intermediates in the transcription process could be visualized and
      analyzed: (1) different multimeric complexes of NtrC(D54E,S160F) dimers bound to
      the DNA template; (2) the closed complex of RNAP x sigma 54 at the glnA promoter;
      (3) association between DNA bound RNAP x sigma 54 and NtrC(D54E,S160F) with the
      intervening DNA looped out; and (4) the activated open promoter complex of RNAP x
      sigma 54. Measurements of the DNA bending angle of RNAP x sigma 54 closed
      promoter complexes yielded an apparent bending angle of 49(+/-24) degrees. Under
      conditions that allowed the formation of the open promoter complex, the
      distribution of bending angles displayed two peaks at 50(+/-24) degrees and
      114(+/-18) degrees, suggesting that the transition from the RNAP x sigma 54
      closed complex to the open complex is accompanied by an increase of the DNA
      bending angle.

PMID- 9236117
TI  - HIV genetic variation is directed and restricted by DNA precursor availability.
AB  - The effects of deoxynucleoside triphosphate (dNTP) imbalances on the fidelity of
      human immunodeficiency virus type 1 (HIV-1) replication were investigated. Using
      detergent permeabilized virions and biased dNTP concentrations different types of
      hypermutants were readily produced. However, the mutant spectrum was different
      from naturally occurring hypermutants demonstrating that the host cell may
      restrict variation. Using a genetic screen based on the blue/white beta
      galactosidase complementation assay, G --> A hypermutants were recovered from HIV
      infected thymidine treated U937 cells. Furthermore, hypermutants were recovered
      from 1 to 2% of resting or activated peripheral blood mononuclear cells
      indicating that small proportions of primary cells had distorted intracellular
      [dTTP] and [dCTP]. Such imbalances may underlie a proportion of somatic and
      germline point mutations and shape to some extent the evolution of mammalian and
      viral genomes.

PMID- 9236118
TI  - A nucleoprotein activation complex between the leucine-responsive regulatory
      protein and DNA upstream of the gltBDF operon in Escherichia coli.
AB  - The global regulator Lrp (leucine-responsive regulatory protein), in some cases
      modulated by its co-regulator leucine, has been shown to regulate more than 40
      genes and operons in Escherichia coli. Leucine modulates Lrp regulation of
      leucine-responsive operons. The level of sensitivity of these operons to leucine
      varies greatly, but the basis for this variation is only partially understood.
      One operon controlled by Lrp that is relatively insensitive to leucine is gltBDF,
      which includes genes specifying the large (GltB) and small (GltD) subunits of
      glutamate synthase. Earlier gel mobility shift assays have demonstrated that Lrp
      binds to a fragment of DNA containing the gltBDF promoter region. To further
      define the nature of this Lrp-gltBDF interaction, DNase I footprinting
      experiments were performed. The results indicate that Lrp binds cooperatively to
      three sites quite far upstream, spanning the region from -140 to -260 base-pairs
      relative to the start of transcription. Phased hypersensitivity is observed
      throughout the entire binding region, suggesting that Lrp bends the DNA. To
      determine the relative importance of these three sites for the transcriptional
      activation of gltBDF, a series of site-directed mutations was generated. The
      effects of these mutations on Lrp binding were determined both by DNase I
      footprinting and by quantitative mobility shift assays, while their effects on
      transcription in vivo were examined by measuring beta-galactosidase activity
      levels of chromosomal gltB::lacZ operon fusions. Our results indicate that all
      three sites are required for maximal gene expression, as is the proper phasing of
      the sites with one another and with the start of transcription. Our results
      suggest that Lrp binds a central palindromic site, interacting predominantly with
      the major groove of its DNA target, and that additional dimers bind to flanking
      sites to form a nucleoprotein activation complex.

PMID- 9236119
TI  - The junction-resolving enzyme T7 endonuclease I: quaternary structure and
      interaction with DNA.
AB  - Endonuclease I is a DNA junction-selective resolving enzyme from bacteriophage
      T7. Using a nuclease-defective mutant that retains normal binding to DNA we show
      that the protein binds to four-way DNA junctions as a dimer, in common with other
      junction-resolving enzymes studied. Gel filtration and chemical crosslinking
      indicate that endonuclease I also exists in free solution as a dimer together
      with a tetramer and higher molecular mass aggregates. However, in marked contrast
      with other junction-resolving enzymes, there is no detectable subunit exchange
      under normal conditions. Only by exposure to 6 M urea could we induce subunit
      exchange, and this was used to generate heterodimeric species containing one
      active and one inactive subunit. Using a supercoil-stabilised cruciform substrate
      we demonstrate that an active subunit of endonuclease I can act as a junction
      specific nuclease in a heterodimeric combination with an inactive subunit.
      However, the two subunits of a fully active homodimeric enzyme each cleave the
      phosphodiester backbone of a cruciform within the lifetime of the DNA-protein
      complex.

PMID- 9236120
TI  - Splicing and intron-internal RNA editing of trnK-matK transcripts in barley
      plastids: support for MatK as an essential splice factor.
AB  - Group II introns frequently require assistance by specific factors, maturases,
      for folding and effective splicing in vivo. The only putative maturase of higher
      plant chloroplasts is encoded by matK, located in the intron of trnK. We show
      that in barley matK transcripts are modified at a first codon base by C-to-U RNA
      editing. The resulting H --> Y substitution restores a sequence motif that is
      present in maturases of yeast and plant mitochondria and of Lactococcus ltrA and
      that is positioned within the X domain. Processing of trnK-matK transcripts was
      further investigated in plastids lacking functional ribosomes due to a mutation.
      Absence of the intron-encoded matK gene product in these plastids is correlated
      with the accumulation of precursor transcripts for tRNALys(UUU)-matK, processed
      to different degrees, and by the lack of mature and spliced tRNA molecules. These
      results suggest an essential role of MatK for splicing of its own transcript in
      vivo. Processing of the 5' end of trnK exon 1 was found to proceed efficiently
      also in the mutant plastids although the two tRNA exons were separated by the
      2481 nt intron. Consequently, presence of the intron does not interfere with the
      formation of mature 5' termini.

PMID- 9236121
TI  - oriT-processing and regulatory roles of TrwA protein in plasmid R388 conjugation.
AB  - TrwA protein was purified from an overproducing Escherichia coli strain and
      characterized as a 53 kDa tetrameric DNA-binding protein. Gel shift assays showed
      that TrwA bound specifically to the oriT sequence of plasmid R388. DNAse I
      footprinting analysis defined two DNA regions within oriT (sites A and B) that
      were protected by TrwA. At low TrwA concentrations only region A was protected
      (K(D) = 4 x 10(-8) M) while region B required higher TrwA concentrations (K(D) =
      4 x 10(-7) M). As a result of its binding to oriT, TrwA was found to perform two
      biochemical activities related to its role in R388 conjugation. First, TrwA
      binding to oriT resulted in transcriptional repression of the trwABC operon as
      indicated by its effect on the beta-galactosidase activity of transcriptional
      fusions in trwB and trwC, and by direct measurement of the trwA mRNA levels by
      hybridization. This result was further confirmed by the fact that TrwA
      overexpression resulted in lowered conjugation frequencies. Second, TrwA enhanced
      the relaxation activity of TrwC in vitro. This effect was correlated to a 10(5)
      fold increase in the frequency of conjugation in vivo and was shown to be
      independent of the regulation of transcription. Thus, TrwA shows functional
      similarities to protein TraY of F-like plasmids, that could be correlated to a
      structural similarity in their DNA-binding motifs.

PMID- 9236122
TI  - Quantitation of the inhibition of Hfr x F- recombination by the mutagenesis
      complex UmuD'C.
AB  - The UmuD'C complex and RecA protein are two essential components in mutagenic
      repair of gaps produced by the replication of damaged DNA. In this process, the
      UmuD'C complex might help DNA polymerase to synthesize DNA across a lesion.
      Besides, a RecA polymer wrapping around single-stranded DNA could function as a
      directional chaperone to target the UmuD'C complex at the lesion. It was shown in
      our laboratory that the UmuD'C complex prevents homologous recombination and
      recombinational repair when expressed at elevated levels. To find out whether the
      UmuD'C complex inhibits recombination by interfering directly with RecA, we
      measured the kinetics of inhibition of Hfr x F- recombination in F- recipients in
      which either RecA or UmuD'C were made to vary. The cell concentrations of RecA
      and UmuD'C proteins were adjusted by having the recA and the umuD'C genes
      regulated by the arabinose P(BAD) promoter. In the absence of the UmuD'C complex,
      recombination was a function of RecA concentration and then reached a plateau
      when the RecA concentration was above 9000 monomers/cell. At a fixed RecA
      concentration, the yield of Hfr x F- recombinants decreased as a function of the
      UmuD'C cell concentration. At a given UmuD'C/RecA ratio, recombination inhibition
      by UmuD'C was reversed by increasing the RecA cell concentration. RecA1730, a
      mutant protein impaired in the chaperone activity, was insensitive to UmuD'C
      inhibition. We propose a model accounting for the RecA chaperone function in SOS
      mutagenesis and for the UmuD'C inhibitory effect on homologous recombination. We
      suggest that the UmuD'C complex is placed at the tip of a RecA polymer as a
      result of a treadmilling process. This would position the UmuD'C complex right at
      a lesion while the capping by UmuD'C would destabilize a RecA polymer and thereby
      abort the recombination process.

PMID- 9236123
TI  - The DNA replication protein PriA and the recombination protein RecG bind D-loops.
AB  - The PriA protein of Escherichia coli provides a vital link between recombination
      and DNA replication. To establish the molecular basis for this link, we
      investigated the ability of PriA to target DNA substrates modelled on D-loops,
      the intermediates formed during the early stages of RecA-mediated recombination.
      We show that PriA binds D-loops and unwinds the DNA in reactions that rely on its
      ability to function as a helicase. The minimal structure that binds PriA is a
      duplex DNA molecule with unpaired single strands at one end, an arrangement
      likely to occur at a D-loop. It resembles features of the stem-loop formed by
      primosome assembly site (PAS) sequences in the DNA of bacteriophage phiX174 and
      plasmid ColE1, and which enable PriA to assemble active primosomes for the
      initiation of lagging strand synthesis. We suggest that PAS sequences may have
      evolved to mimic the natural D-loop target for PriA formed in the chromosome of
      E. coli during recombination and DNA repair. Genetic studies have revealed an
      interaction between PriA and RecG, a DNA helicase that drives branch migration of
      recombination intermediates. We therefore compared PriA and RecG for their
      ability to bind and unwind DNA. RecG, like PriA, binds D-loops and unwinds the
      DNA. However, it prefers branched structures with at least two duplex components.
      The possibility that it competes with PriA for binding recombination
      intermediates is discussed.

PMID- 9236124
TI  - Locations of terminal segments of flagellin in the filament structure and their
      roles in polymerization and polymorphism.
AB  - Terminal regions of flagellin, about 180 NH2 and 100 COOH-terminal residues, are
      well conserved and play important roles in polymerization and polymorphism of
      bacterial flagellar filaments. About 65 NH2 and 45 COOH-terminal residues are
      disordered in the monomeric form, but become folded upon filament formation.
      Taking advantage of the facts that relatively small segments can be cleaved off
      these disordered termini by limited proteolysis, and isolated fragments still
      form straight filaments, locations of those terminal segments have been mapped
      out in the filament structure by electron cryomicroscopy and helical image
      reconstruction. The fragments studied are F(1-486), F(20-494), F(1-461), F(30
      461) and F(30-452). Regardless of the size and terminal side of truncation, the
      structures of the filaments reconstituted from the truncated fragments all have
      identical subunit packing arrangements of the Lt-type symmetry. Structural
      differences compared to the filament reconstituted from intact flagellin are
      found only around the filament axis, namely in the inner-tube region, and no
      obvious changes are observed in the outer-tube or the outer part of the filament.
      Truncation of only a few terminal residues results in misfolding of the inner
      tube domains and their aggregation around the filament axis; further truncation
      reduces the densities of different parts of the aggregate. The filament
      reconstituted from F(30-461) fragment shows complete disappearance of the density
      corresponding to the inner-tube. When a further nine residues are removed, the
      spoke-like features left on the inner wall of the outer-tube become significantly
      smaller. Based on the structures and radial mass distributions of the filaments
      obtained, the previous amino acid sequence assignment to the morphological
      domains has been confirmed and further refined. The roles of terminal segments in
      the assembly regulation, and those of the double-tubular structure in the
      polymorphic mechanism are discussed.

PMID- 9236125
TI  - Bivalent binding of a neutralising antibody to a calicivirus involves the
      torsional flexibility of the antibody hinge.
AB  - The structure of a complex between rabbit haemorrhagic disease virus (RHDV) virus
      like particles (VLPs) and a neutralising monoclonal antibody mAb-E3 has been
      determined at low resolution by cryo-electron microscopy and three-dimensional (3
      D) reconstruction techniques. The atomic co-ordinates of an Fab were fitted to
      the cryo-electron microscope density map to produce a binding model. The VLP has
      a T = 3 icosahedral lattice consisting of a hollow spherical shell with 90
      protruding arches. Each dimeric arch presents two mAb binding sites; however,
      steric hindrance between the variable domains of the Fabs prevents the occupation
      of both sites simultaneously. Thus the maximum mAb occupation is 50%. Once a mAb
      is bound to one site it may bind to either of two neighbouring sites related by a
      local 3-fold axis. The mAbs are bound bivalently on epitopes not related by a 2
      fold symmetry axis. This binding geometry implies a torsional flexibility of the
      mAb hinge region, involving a 60 degrees rotation of one Fab arm with respect to
      the other. Owing to extreme flexibility of the hinge region, the Fc domains
      occupy random orientations and are not visible in the reconstruction. The
      bivalent attachment of mAb-E3 to RHDV suggests that the neutralisation
      mechanism(s) involves inhibition of viral decapsidation and/or the inhibition of
      binding to the receptor.

PMID- 9236126
TI  - Methylation of the Z-DNA decamer d(GC)5 potentiates the formation of A-DNA:
      crystal structure of d(Gm5CGm5CGCGCGC).
AB  - It is well known that methylation of alternating Py x Pu sequences potentiates
      the formation of Z-DNA. However, we have now observed that methylation of the
      alternating Z-DNA oligomer d(GCGCGCGCGC), which starts with a 5'-purine,
      unexpectedly stabilizes the A-DNA conformation. The double methyl derivative
      d(Gm5CGm5CGCGCGC), which crystallizes as duplex A-DNA in the hexagonal space
      group P6(1)22, a = b = 39.33 A and c = 77.93 A with one strand per asymmetric
      unit and six duplexes in the unit cell, refined to an R factor of 19.1 for 204
      DNA atoms and 43 solvent molecules. This is the first report of a DNA sequence
      crystallized in both right and left-handed conformations, allowing structural
      comparisons not previously possible and, more importantly, this is the first time
      that methylation has been shown to potentiate the formation of A-DNA from a
      sequence known to crystallize as Z-DNA. From this study, ten base-pairs appear to
      be the critical length in determining the handedness of d(GC)n-type sequences in
      the crystalline state. Because methylation of nuclear DNA is linked to a number
      of cellular processes, including transcriptional inactivation, this study has
      important implications for the role of A-DNA in methylated regions of genomic DNA
      and, thus, in the regulation of gene expression. In this context, the structure
      of d(Gm5Cm5CGCGCGC) will be compared with that of the alternating A-DNA decamer
      d(GCACGCGTGC) and the alternating Z-DNA decamer d(GCGCGCGCGC) and discussed in
      terms of the forces that govern the handedness of duplex DNA oligomers.

PMID- 9236127
TI  - The crystal structure of an Fe-superoxide dismutase from the hyperthermophile
      Aquifex pyrophilus at 1.9 A resolution: structural basis for thermostability.
AB  - Superoxide dismutase (SOD) from Aquifex pyrophilus, a hyperthermophilic
      bacterium, is an extremely heat-stable enzyme that maintains about 70% of its
      activity after heat treatment for 60 minutes at 100 degrees C. To understand the
      molecular basis of thermostability of this enzyme, we have determined the crystal
      structure of A. pyrophilus superoxide dismutase (Ap SOD), an Fe containing
      homotetrameric enzyme, at 1.9 A resolution, and compared it with SOD structures
      from a mesophile and a thermophile, and other enzyme structures from other
      hyperthermophiles. The structure has been refined to a crystallographic R-factor
      (I > 2sigma) of 17.0% and R-free (I > 2sigma) of 19.9%. While the overall
      structure of the Ap SOD monomer is similar to the other SODs, significant
      conformational differences are observed in a highly variable loop region and the
      C-terminal helix. The conformational differences in these regions alter the
      subunit arrangement of this enzyme and generate a very compact tetramer.
      Structural comparisons of three SODs have revealed that Ap SOD has some
      stabilizing features at both the tertiary and the quaternary structural level:
      The Ap SOD monomer contains a large number of ion-pairs and the Ap SOD tetramer
      has a dramatically increased buried surface area per monomer. Comparisons of the
      Ap SOD structure with that of other known enzymes from hyperthermophiles reveal
      that the increased number of intrasubunit ion-pairs is a common feature.

PMID- 9236128
TI  - Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain.
AB  - Type I collagen is the most prevalent member of the fibril forming family of
      collagens in higher vertebrates and its heterotrimeric form is comprised of two
      alpha 1(I) chains and one alpha2(I) polypeptide chain. The functional importance
      of having two distinct chain types in type I collagen is largely undefined. The
      existence of a mouse model with a Cola-2 gene mutation (termed oim) that results
      in non-functional pro alpha 2(I) chains presents a unique opportunity to explore
      changes in collagen structure resulting from the complete (oim/oim mice) and
      partial (oim/+ mice) loss of functional alpha 2(I) chains. Tail tendon is a
      tissue with a well-defined, hierarchical organization of type I collagen. X-ray
      diffraction studies on oim/oim versus control tendons indicate that the total
      absence of alpha 2(I) chains results in a decrease in the order of axial packing
      and a loss of crystalline lateral packing. This suggests that the non-equivalence
      of three chains is an important determinant of lateral interactions between
      adjacent molecules and may be involved in the long-range axial order in type I
      collagen-containing tissues. Both homotrimeric and heterotrimeric type I collagen
      molecules are found in heterozygous oim mice and these appear to be present in
      the same co-polymeric fibrils, preventing crystalline lateral packing. In
      addition to these changes at a fibrillar level, the absence of the alpha 2(I)
      chain results in an increased enzymatic susceptibility at one site. The oim/oim
      mice are observed to have reduced body size and smaller tendon bundles, which may
      be a consequence of these molecular and fibrillar changes in collagen.
      Furthermore, it is likely that a similar alteration in the molecular packing of
      collagen in bone fibrils contributes to the osteopenia and decreased bone
      strength in mice with the oim mutation that are also characteristic of human
      osteogenesis imperfecta.

PMID- 9236129
TI  - Helix proximity and ligand-induced conformational changes in the lactose permease
      of Escherichia coli determined by site-directed chemical crosslinking.
AB  - N and C-terminal halves of lactose permease, each with a single-Cys residue, were
      co-expressed, and crosslinking was studied. Iodine or N,N'-o-phenylenedimaleimide
      (o-PDM; rigid 6 A), crosslinks Asn245 Cys (helix VII) and Ile52 --> Cys or Ser53 
      -> Cys (helix II). N,N'-p-phenylenedimaleimide (p-PDM; rigid 10 A) crosslinks the
      245/53 Cys pair weakly, but does not crosslink 245/52, and 1,6-bis
      maleimidohexane (BMH; flexible 16 A) crosslinks both pairs less effectively than
      o-PDM. Thus, 245 is almost equidistant from 52 and 53 by up to about 6 A. BMH or
      p-PDM crosslinks Gln242 --> Cys and Ser53 --> Cys, but o-PDM is ineffective,
      indicating that distance varies by up to 10 A. Ligand binding increases
      crosslinking of 245/53 with p-PDM or BMH, has little effect with o-PDM and
      decreases iodine crosslinking. Similar effects are observed with 245/52. Ligand
      increases 242/53 crosslinking with p-PDM or BMH, but no crosslinking is observed
      with o-PDM. Therefore, ligand induces a translational or scissors-like
      displacement of the helices by 3-4 A. Crosslinking 245/53 inhibits transport
      indicating that conformational flexibility is important for function.

PMID- 9236130
TI  - Three-state model for lysozyme folding: triangular folding mechanism with an
      energetically trapped intermediate.
AB  - We investigated the role of a partially folded intermediate that transiently
      accumulates during lysozyme folding. Previous studies had shown that the
      partially folded intermediate is located on a slow-folding pathway and that an
      additional fast direct pathway from the unfolded state to the native state
      exists. Kinetic double-jump experiments showed that the two folding pathways are
      not caused by slow equilibration reactions in the unfolded state. Rather, kinetic
      partitioning occurs very early in lysozyme refolding, giving the molecules the
      chance to enter the direct pathway or a slow-folding channel. Fitting the
      guanidinium chloride dependencies of the refolding and unfolding reactions to
      analytical solutions for different folding scenarios enables us to propose a
      triangular mechanism as the minimal model for lysozyme folding explaining all
      observed kinetic reactions: [diagram in text]. All microscopic rate constants and
      their guanidinium chloride dependencies could be obtained from the experimental
      data. The results suggest that population of the intermediate during refolding
      increases the free energy of activation of the folding process. This effect is
      due to the increased stability of the intermediate state compared to the unfolded
      state leading to an increase in the free energy of activation (deltaG0) compared
      to folding in the absence of populated intermediate states. The absolute energy
      of the transition state is identical on both pathways. The results imply that pre
      formed secondary structure in the folding intermediate obstructs formation of the
      transition state of folding but does not change the nature of the rate-limiting
      step in the folding process.

PMID- 9236131
TI  - Thermodynamics of a reverse turn motif. Solvent effects and side-chain packing.
AB  - The linear pentapeptide, Ala-Tyr-cis-Pro-Tyr-Asp-NMA (AYPYD) is known to have a
      significant population of type VI turn conformers in aqueous solvent. We have
      carried out theoretical studies of the conformational energetics of this peptide
      using a potential of mean force (PMF) consisting of the AMBER/OPLS empirical
      potential energy function, a macroscopic electrostatic model of polar solvation,
      and a surface area-based model of non-polar solvation. Conformers were taken from
      molecular dynamics simulations reported elsewhere, or generated by a random
      search method reported here. The chain entropy of folding was calculated by a
      systematic search of accessible dihedral angle space. The intra-peptide component
      was found to strongly favor folding and was nearly cancelled by the polar
      solvation term which disfavored folding. The non-polar solvation term had little
      effect. Fluctuations about the average value of the PMF were small and in accord
      with estimates from a simple harmonic model. When applied to conformers generated
      by a random search, the PMF selected a conformer close to the NMR-determined
      structure as the lowest energy conformer. The conformer with the second-lowest
      energy was extended, but was found to fold rapidly to the turn state in a
      subsequent molecular dynamics study, and may be an important state on the folding
      unfolding pathway. Averages of the PMF were combined with the entropy estimates
      to provide an estimate of the free energy of folding that is in reasonable
      agreement with experimental results. In terms of the interplay between backbone
      electrostatic interactions and the packing of apolar side-chains, this peptide
      provides a model for the energetics of protein folding, and therefore makes a
      useful test case for calculations.

PMID- 9236132
TI  - Differential and dramatic changes of cyclin-dependent kinase activities in
      cardiomyocytes during the neonatal period.
AB  - The molecular mechanisms that arrest cardiomyocytes in the cell cycle during the
      postnatal period remain largely unknown. We have examined changes of the
      expression of cyclins and CDKs, the activity of each CDK in cardiomyocytes during
      the postnatal period, and have compared those changes with rate of binucleation
      formation of cardiomyocytes in rats. The mRNA and protein levels of cyclin D1, A
      and B in cardiomyocytes were high at day 1, then the levels decreased at
      different rates during the postnatal period. While the protein levels of cyclin A
      and B rapidly decreased, the protein level of cyclin D1 was relatively constant.
      The protein levels of CDK4, CDK2, and cdc2 in cardiomyocytes were high at day 1,
      then their levels gradually decreased. However, the activity of CDK4, which is
      responsible for G1 phase of cell cycle, was detectable only at day 1. The
      activity of CDK2 activity, which is responsible for the S phase of cell cycle,
      was relatively high at day 1, decreased at day 2, abruptly decreased at day 4,
      maintained the same low level until day 10, and barely or not detectable
      thereafter in cardiomyocytes. The activity of cdc2 was high at day 1, increased
      by 20% at day 2, and then gradually decreased thereafter, although approximately
      50% of maximum activity was present at day 6. Most cardiomyocytes were
      mononucleated during the first 2 days postnatal. The percentage of binucleated
      cardiomyocytes increased from 2.5% at day 2, 14% at day 4, 50% at day 8, 80% at
      day 14, and had reached adult levels at day 21 after birth. During active
      binucleation formation in neonatal (from days 1-14) cardiomyocytes, CDK4 or CDK2
      was functionally negligible, while cdc2 was functionally active. These data
      suggest that there were differential and dramatic decrease of CDK4 and CDK2
      activities in cardiomyocytes during neonatal period, and the functionally active
      cdc2 in neonatal cardiomyocytes may be involved in binucleation formation.

PMID- 9236133
TI  - Nitric oxide modulates basal and endothelin-induced coronary artery vascular
      smooth muscle cell proliferation and collagen levels.
AB  - The mechanisms governing the pathological accumulation of collagen in the
      extracellular matrix following angioplasty are complex, but may involve
      interactions between endothelium-derived paracrine agents and vascular cellular
      components. We tested the hypothesis that nitric oxide (NO) directly decreases
      collagen levels and decreases endothelin (ET-1)-stimulated increases in levels of
      specific collagen subtypes in coronary vascular smooth muscle cells (VSMC).
      Cultured VSMC were incubated for 48 h with the NO donor CAS 754 (10(-4) M), ET-1
      (10(-8) M), or ET-1 plus CAS 754. In some experiments, angiotensin II (Ang II;
      10(-8) M) was utilized in place of ET-1. Soluble collagen types I and III were
      quantitated with an ELISA method, and cell counts were performed. CAS 754
      significantly inhibited cell proliferation (-17+/-2% v control), basal total
      protein synthesis (-65+/-7% v control), and basal collagen type I levels (-39+/
      6% v control), but not collagen type III levels. ET-1 and Ang II both
      significantly stimulated cell proliferation (26+/-5% v control), total protein
      synthesis (169+/-6% v control), and collagen type I levels (200+/-11% v control).
      Ang II, but not ET-1, significantly increased collagen type III levels. Co
      incubations of ET-1 and CAS 754 resulted in a significant decrease in cell
      proliferation, protein synthesis, and collagen levels (-23+/-2% v control, 90+/
      5% v control, and 63+/-3% v control, respectively) compared to ET-1 alone. In
      contrast, co-incubation of Ang II and CAS 754 had no significant effect on cell
      proliferation, protein synthesis, and collagen levels seen with Ang II alone.
      These results demonstrate that NO inhibits basal collagen levels and cell
      division. Additionally, NO alters ET-1 stimulation of VSMC proliferation, protein
      synthesis, and production of extracellular matrix components. Thus, an imbalance
      in key endothelium-derived compounds could significantly impact upon
      extracellular matrix deposition following mechanical revascularization.

PMID- 9236134
TI  - Expression of calcium channels in adult cardiac myocytes is regulated by calcium.
AB  - In addition to playing a significant role in cardiac excitation-contraction
      coupling, intracellular Ca2+ ([Ca2+]i) can regulate gene expression. While the
      mechanisms regulating expression of Ca2+ channels are not entirely defined, some
      evidence exists for Ca2+-dependent regulation. Using an adult ventricular myocyte
      culture system, we determined the effects of Ca2+ on: (1) abundance of mRNA for L
      type Ca2+ channel alpha1 subunit (DHP receptor); (2) amount of DHP receptors; and
      (3) whole-cell Ca2+ current (ICa). Rat ventricular myocytes were cultured for 1-3
      days in serum-free medium containing either normal (1.8 mM) or high (4.8 mM)
      Ca2+. Exposing myocytes to high Ca2+ rapidly elevated [Ca2+]i as determined by
      fura-2. Northern blot analysis revealed that culturing cells in high Ca2+
      produced 1.5-fold increase in mRNA levels for the DHP receptor. The abundance of
      DHP receptors, determined by ligand binding, was two-fold greater in myocytes
      after 3 days in high Ca2+. Moreover, peak ICa was larger in myocytes cultured for
      3 days in high Ca2+ (-17.8+/-1.5 pA/pF, n=26) than in control cells (-11.0+/-1.0
      pA/pF, n=23). Voltage-dependent activation and inactivation, rates of current
      decay, as well as percent increases in ICa elicited by Bay K8644 were similar in
      all groups. Therefore, larger ICa is likely to represent a greater number of
      functional channels with unchanged kinetics. Our data support the conclusion that
      transient changes in [Ca2+]i can modulate DHP receptor mRNA and protein
      abundance, producing a corresponding change in functional Ca2+ channels in adult
      ventricular myocytes.

PMID- 9236135
TI  - Heat shock-induced manganese superoxide dismutase enhances the tolerance of
      cardiac myocytes to hypoxia-reoxygenation injury.
AB  - We evaluated the mechanism of the heat shock-induced tolerance to ischemia
      reperfusion using a model of hypoxia-reoxygenation tolerance in neonatal rat
      cardiac myocytes. Myocytes exposed to heat shock (42 degrees C, 1 h) exhibited a
      1.8-fold increase in levels of manganese superoxide dismutase (Mn-SOD) mRNA after
      40 min v control cells. The concentration of Mn-SOD increased from 0.49+/-0.04
      microg/mg protein to 0.68+/-0.05 microg/mg protein after 24 h (P<0. 05). Levels
      of heat shock protein 72 (hsp72; inducible form) mRNA and protein also increased
      markedly after heat shock exposure. The release of creatine kinase (CK) from the
      myocytes and the depletion of ATP level in the myocytes exposed to hypoxia (pO2:
      7 mmHg, 3 h) and reoxygenation (pO2: 143 mmHg) were significantly reduced
      following heat shock pretreatment (CK: 1.18+/-0.14 U/l v 0.62+/-0.13 U/l, ATP:
      11.9+/-1.1 nmol/mg protein v 16.2+/-1.0 nmol/mg protein, P<0.05). Treatment with
      antisense oligodeoxyribonucleotides to Mn-SOD (1.5 micromol/l) completely
      inhibited the heat shock-associated induction of Mn-SOD (0.47+/-0.05 microg/mg
      protein), but not hsp72, and abolished the heat shock-induced decrease in CK
      release (1.04+/-0.15 U/l, P<0.05) and depletion of ATP level (11. 2+/-1.1 nmol/mg
      protein, P<0.05). Results indicate that Mn-SOD induction, not hsp72 induction,
      plays a pivotal role in the heat shock-induced acquisition of tolerance to
      hypoxia-reoxygenation in neonatal rat cardiac myocytes.

PMID- 9236136
TI  - Time course of tolerance to ischemia-reperfusion injury and induction of heat
      shock protein 72 by heat stress in the rat heart.
AB  - We compared the time course of tolerance to myocardial ischemia-reperfusion
      injury with the time course of heat shock protein 72 (hsp72; inducible form)
      induction after heat stress in a rat model. The size of the infarct resulting
      from ischemia-reperfusion was increased 12 h after whole-body hyperthermia (42
      degrees C for 15 min), but was significantly decreased 48 and 72 h after
      hyperthermia, compared with the sham control. The infarct size was decreased as
      late as 96 h after hyperthermia, although the infarct-limiting effect was smaller
      at that time. The myocardial content of hsp72 was markedly increased for 3-72 h
      after hyperthermic treatment, and was decreased after 72 h in association with an
      increase in the infarct size. The hsp72 content remained elevated during the
      period of tolerance to ischemia-reperfusion injury, but the infarct size
      decreased after the hsp72 content peaked. Pretreatment with a protein kinase C
      (PKC) inhibitor, chelerythrine chloride, immediately before hyperthermia,
      significantly suppressed the delayed cardioprotective effect of hyperthermia and
      reduced hsp72 induction. These results suggest that newly synthesized hsp72
      through PKC activation after heat stress may have to be post-translationally
      modified and compartmentalized prior to assuming to the development of the
      delayed tolerance to ischemia-reperfusion injury in rats.

PMID- 9236137
TI  - Cellular basis of contractile derangements of hypertrophied feline ventricular
      myocytes.
AB  - The objective of this study was to further explore the cellular basis of the
      reduced rate and magnitude of contraction of feline left ventricular myocytes
      with severe hypertrophy induced by slow progressive pressure overload. A 3.0 mm
      internal diameter band was placed around the ascending aorta of 12 young (8-10
      weeks old) cats, and sham operations were performed in 13 others. This caused no
      major pressure overload initially, but 15 weeks later there was a significant
      pressure gradient across the band (56+/-14 mmHg) and the heart weight to body
      weight ratio had increased from 4.2-7 gm/kg. Contraction rates and magnitudes of
      myocytes isolated from the hearts with hypertrophy (LVH) were significantly
      slower and smaller, respectively, than those from control (C) animals. Indo-1
      fluorescence transients in LVH myocytes were significantly smaller in magnitude
      and longer in duration than in C, suggesting that contractile defects result from
      Ca2+ derangements. Elevation of bath Ca2+ increased the peak Indo-1 fluorescence
      and the rate and magnitude of contraction in all myocytes. At the bath Ca2+ which
      had maximal inotropic effects there were no differences in the peak Indo-1
      fluorescence in LVH and C myocytes, but contraction magnitude remained
      significantly smaller in LVH. This suggests that there are Ca2+-independent
      contractile derangements in LVH. In support of this hypothesis, the relationship
      between contraction magnitude and the peak Indo-1 fluorescence (index of
      myofibrillar Ca2+ sensitivity) was significantly shifted in LVH myocytes,
      suggesting that myofibrillar Ca2+ sensitivity was reduced. There was also a
      significant shift of the terminal portions of hysteresis loops of cell length v
      indo-1 fluorescence ratio, providing additional support for this idea.
      Experiments with isoproterenol suggest that it can reduce myofibrillar Ca2+
      sensitivity in C, but not LVH myocytes. The idea that increased internal
      resistance to shortening (internal load) is responsible for the contractile
      defects of LVH myocytes was examined by defining the relationship between the
      rate of relengthening and the magnitude of shortening. There was no significant
      difference in this relation between C and LVH myocytes. In addition, colchicine
      (which depolymerizes microtubular tubulin) had no significant effect on
      contraction magnitude in either C or LVH myocytes. These results suggest that the
      contractile properties of feline LVH myocytes result from changes in cellular
      Ca2+ regulation and myofibrillar Ca2+ sensitivity, but not from changes in the
      internal loading.

PMID- 9236138
TI  - Cardiac collagen remodeling in the cardiomyopathic Syrian hamster and the effect
      of losartan.
AB  - Although increased deposition of collagen proteins has been described in
      cardiomyopathy, little is known of the temporal relationship between events in
      collagen gene transcription and the occurrence of cardiac fibrosis, the removal
      of collagen by matrix metalloproteinases (MMPs), or of the regulation of these
      events by angiotensin AT1 receptors in this disease. We sought to study steady
      state collagen mRNA abundance and the deposition of specific collagen subtypes in
      right and left ventricular muscle of Syrian cardiomyopathic (CMP) hamsters at
      different stages of cardiomyopathy. Using zymography, we also investigated the
      gelatinolytic activities of different MMPs to gain some information about
      collagen removal in experimental hearts. Finally, we investigated the effect of
      AT1 receptor blockade (losartan) on collagen remodeling. We observed that the
      mRNA levels of types I and III collagens were significantly increased in all four
      experimental groups (35, 65, 120, and 200 day) in left ventricular tissue when
      compared to control (F1-beta strain) values. The mRNA levels of these collagen
      species in experimental right ventricular tissue samples were only elevated
      significantly in the 35 and 200 day experimental groups when compared to
      controls. Fibrillar collagen deposition was elevated in left and right
      ventricular CMP samples after a lag period from the occurrence of corresponding
      increases in mRNA abundance. Although 2-week losartan treatment of 65, 120 and
      200 day experimental groups had no significant effect on left ventricular
      fibrillar collagen concentration or collagen mRNA abundance when compared to
      vehicle-infused CMP hamsters, AT1 receptor blockade was associated with complete
      regression of cardiac hypertrophy. Both MMP-1 (54 kDa band) and MMP-2 (58 and 62
      kDa bands) activities were increased in left ventricular CMP tissues at 65, 120
      and 200 days when compared to F1-beta controls. Losartan treatment was associated
      with significant attenuation of MMP activities in cardiomyopathic samples at 65
      and 120 days. Thus, elevation of mRNA abundance of fibrillar collagen genes
      occurs at very early stages in this model of cardiomyopathy, and corresponding
      collagen proteins were subsequently deposited in the cardiac interstitium at
      later stages. As collagen concentration was significantly increased in later
      stages of cardiomyopathy studied herein (120 and 200 day groups), our data
      support the hypothesis that collagen synthesis exceeds the capacity of collagen
      removal during the progression of cardiomyopathy. Nevertheless, cardiac collagen
      remodeling may be facilitated by elevated MMP activity in cardiomyopathic stages
      in this experimental model, and we suggested that attenuation of MMP activity in
      the presence of losartan may be a cardioprotective mechanism of this agent.

PMID- 9236139
TI  - Participation of nitric oxide signaling system in the cardiac muscarinic
      cholinergic effect of human chagasic IgG.
AB  - The possible role of altered humoral immune response in the pathogenesis of the
      chronic chagasic cardioneuromyopathy was examined by analyzing the interaction of
      IgG from T. cruzi infected patients with cardiac muscarinic acetylcholine
      receptors (mAChR). Human chagasic IgG by activating cardiac M2 mAChR, simulated
      the agonist actions triggering negative inotropic effect, inositol phosphate
      accumulation, nitric oxide synthase stimulation and increased production of
      cyclic GMP. Inhibitors of phospholipase C, protein kinase C, calcium/calmodulin,
      nitric oxide synthase and guanylate cyclase activities; prevented chagasic IgG
      effects on signaling pathways involved in M2 mAChR activation. In addition,
      sodium nitroprusside or 8-bromo cyclic GMP, mimicked the chagasic IgG effect
      associated with cholinergic-mediated cellular transmembrane signals. Moreover,
      these chagasic IgG immunoprecipitated the mAChRs solubilized from cardiac
      membranes. By means of SDS-PAGE and immunoblotting analysis, chagasic sera
      recognized a band of 70-75 kDa. The major protein recognized by chagasic IgG had
      an Rf coincident with the peak of [3H] propylbenzilylcholine mustard with an
      apparent molecular weight similar to that of mAChRs, which disappeared in the
      presence of atropine. The specificity of this interaction was checked by
      immunoprecipitation of rat cardiac mAChR and immunoblotting of pure human M2
      mAChRs. Chronic interaction of chagasic IgG with myocardial mAChRs, behaving as a
      muscarinic agonist, might lead to cell dysfunction or tissue damage. Also, these
      antibodies could produce desensitization, internalization or degradation of
      mAChRs; explaining the progressive blockade of mAChRs in myocardium with
      parasympathetic denervation, a phenomenon that has been described in the course
      of Chagas' cardioneuromyopathy.

PMID- 9236140
TI  - Molecular mechanisms underlying the long-term impact of dietary fat to increase
      cardiac pyruvate dehydrogenase kinase: regulation by insulin, cyclic AMP and
      pyruvate.
AB  - Previous studies have demonstrated that pyruvate dehydrogenase kinase (PDHK)
      activity in extracts of rat cardiac mitochondria is increased @two-fold by
      providing a high-fat diet for 28 days. The present study sought to establish the
      factor(s) that might underlie the response of cardiac PDHK to the provision of a
      high-fat diet. ELISA assays of PDHKII, conducted over a range of PDHK activities,
      demonstrated that the increase in cardiac PDHK activity was not due to an
      increase in mitochondrial immunoreactive PDHKII concentration. The pyruvate
      concentration giving 50% active PDHC (PDHa) in mitochondria incubated with
      respiratory substrates was unaffected by high-fat feeding, demonstrating a
      dissociation between increased PDHK activity and altered sensitivity of PDHK to
      suppression by pyruvate. In cardiac myocytes cultured (25 h) with n-octanoate (1
      mm) plus dibutyryl cAMP (50 microM), insulin at 12.5 microU/ml, 25 microU/ml and
      75 microU/ml, suppressed PDHK activities in cells prepared from control rats, but
      insulin at concentrations <100 microU/ml failed to suppress PDHK activities in
      cardiac myocytes prepared from high-fat-fed rats. In vivo, cardiac insulin
      sensitivity (assessed by euglycaemic hyperinsulinaemic clamp in combination with
      2-[3H] deoxyglucose administration) was suppressed after high-fat feeding. A
      sustained (24 h) two- to four-fold elevation in plasma insulin concentration
      (achieved by insulin infusion via osmotic pumps) did not affect PDHK activity in
      hearts of control rats. In contrast, PDHK activity in hearts of high-fat-fed rats
      was suppressed to values not significantly different from (insulin-infused)
      control rats. Basal and agonist-stimulated cAMP concentrations were unaffected by
      high-fat-feeding or insulin. Furthermore, rates of palmitate oxidation (to CO2)
      in cardiac myocytes (in the absence or presence of insulin or adrenergic
      agonists) were not statistically significantly affected by high-fat-feeding. The
      results indicate that an impaired action of insulin to suppress PDHK participates
      in the mechanism by which increased PDHK activity is achieved in response to high
      fat feeding, but insulin does not act through decreasing cAMP concentrations or
      suppressing fatty acid oxidation.

PMID- 9236141
TI  - A major involvement of the cardiovascular system in patients affected by Marfan
      syndrome: novel mutations in fibrillin 1 gene.
AB  - The aim of our study was to characterize the molecular defect in Italian Marfan
      patients, thus contributing to the effort of correlating the genotype with the
      phenotype. In particular, our ultimate goal was to identify the region(s) of the
      fibrillin 1 (FBN1) gene mainly involved in the health of the heart and of the
      aorta in terms of the cardiovascular system. We searched for a molecular defect
      in three patients with classic Marfan syndrome (MFS). The mutations were detected
      applying heteroduplex analysis to each of the 65 exons of the FBN1 gene amplified
      by polymerase chain reaction (PCR). Exons containing heteroduplex bands were
      sequenced directly from PCR products. This study reports the detection of three
      unique missense mutations in the FBN1 gene in three Italian patients: a 44-year
      old adult male and 36-year-old female affected by classic MFS (with all the
      cardinal manifestations in the cardiovascular, ocular and skeletal systems), and
      an 11-year-old male affected by infantile (earlier onset) classic MFS. The first
      two are sporadic cases and present a Cys-->Arg amino acid substitution (T-->C
      substitution at nucleotide 7729) in exon 62 and a Cys-->Tyr amino acid
      substitution (G-->A substitution at nucleotide 6695) in exon 54. The third is a
      familial case which presents a Cys-->Trp aminoacidic substitution (C-->G
      substitution at nucleotide 3546) in exon 28. Our data confirm that cysteine
      substitutions in calcium binding epidermal growth factor (cbEGF)-like domains
      cause severe Marfan phenotype. Exon 24-32 cluster seems to produce an even more
      severe phenotype. The early characterization may be of clinical relevance for
      prevention and early surgical treatment of aortic aneurysm or dissection.

PMID- 9236142
TI  - Genistein, a tyrosine kinase inhibitor, blocks the "second window of protection"
      48 h after ischemic preconditioning in the rabbit.
AB  - We have previously reported a delayed or "second window of protection" against
      infarction 24-72 h after ischemic preconditioning in the rabbit. This phenomenon
      has also been associated with the protein kinase C signalling pathway. In the
      present study, we expanded our investigation to ascertain whether protein
      tyrosine kinase was in any way associated with this phenomenon in the rabbit
      heart. We found that 48 h after ischemic preconditioning with 4x5 min coronary
      occlusions the percentage of myocardium infarcting within the risk zone following
      a 30-min coronary occlusion and 120-min reperfusion (I/R) was reduced from 39.
      6+/-3.3% to 18.0+/-3.7% (P<0.01). However, an i.v. bolus administration of
      genistein (5 mg/kg), a tyrosine kinase inhibitor, 5 min before ischemic
      preconditioning stimulus, abolished this protection (I/R=39.0+/-3.4%). Genistein
      per se had no significant effect on infarction 48 h later. Risk zone volume after
      coronary ligation was not significantly different between intervention groups.
      There were no differences in hemodynamic parameters between groups throughout the
      experimental period. We conclude that the second window of protection, 48 h after
      preconditioning, is mediated by tyrosine kinase activation in the rabbit heart.

PMID- 9236145
TI  - Effect of endotoxin and platelet-activating factor on lipid oxidation in the rat
      heart.
AB  - The effects of endotoxin and platelet-activating factor (PAF) administered in
      vivo and in vitro on lipid oxidation by isolated perfused working rat heart were
      investigated and compared. Endotoxin administered in vivo decreased oleate
      oxidation in perfused hearts and caused increased accumulation of lipid in
      myocardial tissue; this was accompanied by a dose-dependent inhibition of cardiac
      mechanical function. There was no effect on triolein (chylomicron) oxidation. By
      contrast, PAF administered in vivo caused a small (non-significant) increase in
      the oxidation rate of oleate and triolein, and also increased myocardial
      lipoprotein lipase activity. Cardiac mechanical function was not inhibited by PAF
      indeed pretreatment of animals by PAF administered in vivo protected the heart
      from the decline in function associated with subsequent fatty acid perfusion.
      Administration of endotoxin during perfusion in vitro did not affect oleate or
      triolein oxidation and cardiac mechanical function was unchanged; PAF
      administered in vitro caused an early increase in oleate oxidation and a later
      increase in triolein oxidation. Administration of both endotoxin and PAF in vitro
      increased myocardial lipoprotein lipase activity. PAF is unlikely to be
      responsible for all of the effects of endotoxin on cardiac lipid metabolism.

PMID- 9236143
TI  - Inhibition of cardiac myocyte division in c-myc transgenic mice.
AB  - Overexpression of the c-myc protooncogene in the heart of transgenic mice has
      been demonstrated to result in cardiac enlargement due to increased myocyte
      hyperplasia during the fetal period. To determine the age of completion of the
      proliferative phase of myocyte growth in neonatal mice with c-myc overexpression,
      we used a transgenic (TG) mouse model in which c-myc overexpression is limited to
      the heart. Bromodeoxyuridine (BrdU) was given to TG and wild type (WT) mice
      (n=3/group) at 1, 2, 3, 5, 7, 10, 14, 16, 18 and 20 days of age to identify cells
      in S-phase of the cell cycle. Increased cardiac mass was present in TG compared
      to WT mice at all time periods (P<0. 05). Using computer assisted image analysis,
      myocardial total nuclear density (NT) in TG mice was 7-31% greater in both the
      left ventricle (LV) and the interventricular septum (IVS) than in WT at all ages
      (P<0.05), indicative of a smaller myocyte size. In WT mice, the labeling index
      (LI) remained almost constant at approximately 11-12% until 7 days of age, and
      then rapidly dropped to approximately 2% by 14 days and to less than 1% by 20
      days. In contrast, LI in TG dropped continuously from birth to approximately 4%
      at 7 days and approximately 2% at 10 days of age (P<0.001). Thus, overexpression
      of the c-myc protooncogene is associated with enhanced hyperplastic growth of the
      heart during fetal development, and accelerated neonatal conversion to
      hypertrophic myocyte growth.

PMID- 9236144
TI  - Energy metabolism in normal and hypertrophied right ventricle of the ferret
      heart.
AB  - Using an isolated ferret heart preparation (Langendorff perfusion, perfusion
      pressure 90 mmHg), energy metabolism has been characterized in right and left
      ventricles from control and hypertrophied hearts. Hypertrophy was induced by
      pulmonary artery clipping for 30-45 days (right ventricle wall weight/body weight
      ratio increased by 70%). Myocardial contents of high energy phosphate compounds,
      glycogen and lactate, and the activities of some enzymes were biochemically
      measured in perfused hearts and also after ischemic arrest (30 min global
      ischemia). In hypertrophied right ventricles, PCr (-46%), Cr (-34%) levels,
      creatine kinase activity (-18%) were significantly decreased compared with
      control. ATP and Pi levels were not affected by hypertrophy. The adenylate energy
      charges were similar (0.85-0.86) in both types of heart. The activities of
      hexokinase (+26%), aldolase (+212%), pyruvate kinase (+14%) and glucose 6
      phosphate dehydrogenase (+107%) were increased by hypertrophy. The LDH isozyme
      pattern was significantly changed such that LDH3 was decreased by 11%, and LDH4
      and LDH5 were increased by a factor 1.4 and 2.9 respectively in hypertrophy.
      After 30 min of global ischemia, PCr level was decreased by 89 and 79% in control
      and hypertrophied ventricles respectively. ATP level was depressed by 41 in
      control and only by 21% in hypertrophied muscles. Altogether, the present data
      suggested that, in the adult ferret heart, the capacity for the ATP synthesis
      could be maintained during hypertrophy by the enhancement of the glycolytic
      pathway. The smaller decline of ATP after ischemia in hypertrophied tissue could
      be explained by a lower consumption of ATP in the hypertrophied compared to the
      control heart during the earliest period of ischemia.

PMID- 9236146
TI  - Induction of heat shock proteins by tyrosine kinase inhibitors in rat
      cardiomyocytes and myogenic cells confers protection against simulated ischemia.
AB  - Previous studies have shown that in rodent myogenic cells and in the hearts of
      transgenic mice in which heat shock protein expression is increased there is a
      marked tolerance to ischemic/reperfusion injury. Furthermore, a recent study has
      shown that the benzoquinoid ansamycin antibiotic and tyrosine kinase inhibitor,
      herbimycin A, is capable of inducing the expression of heat shock proteins in
      fibroblasts. Our intention, in the present study, was to investigate if exposure
      of rat cardiomyocytes and the myogenic cell line H9c2 to herbimycin A would
      induce these proteins and, thus, confer protection against ischemic stress. For
      this purpose, we exposed both rat neonatal cardiomyocytes and H9c2 cells to
      herbimycin A and another related benzoquinoid ansamycin antibiotic, geldanamycin.
      We found that cells exposed to these compounds overexpressed heat shock proteins
      and are also rendered more tolerant to simulated ischemia as measured by the
      release of cytoplasmic enzymes. In addition, we found that the mechanism of
      induction of heat shock proteins by these compounds is similar, if not identical,
      to that of a heat shock (42 degrees C, 60 min). These results suggest that these
      benzoquinoid ansamycin antibiotics, or closely related analogues, may offer a
      pharmacological means of increasing the level of heat shock proteins in cardiac
      tissue and thus protect the heart against ischemic/reperfusion injury.

PMID- 9236147
TI  - Left ventricular regional myocyte contractility in normal and heart failure
      states.
AB  - Fundamental determinants of left ventricular (LV) pump performance are preload,
      afterload and myocyte contractility. Regional variability in LV end systolic wall
      stress, an important index of LV afterload, has been well defined in both control
      and congestive heart failure (CHF) states. The goal of this study was to examine
      end systolic wall stress and myocyte contractile function in three
      circumferential regions of the LV in both control and CHF states. Accordingly, LV
      end systolic wall stress and myocyte velocity of shortening were measured from
      the basal, mid and apical regions in control pigs (n=5) and following the
      induction of pacing-induced CHF (3 weeks, 240 beats/min, n=5). LV mid wall,
      circumferential, end systolic wall stress decreased from base to apex in both
      control (35+/-7 v 16+/-4 g/cm2, P<0.05) and CHF (155+/-23 v 92+/-24 g/cm2,
      P<0.05) states. In the CHF group, LV end systolic wall stress was elevated by
      300% compared to control values in all regions. LV myocyte velocity of shortening
      was equivalent in the basal and mid regions of control myocytes (52+/-2 v 57+/-2
      m/s), and was higher in the apical region (63+/-3 microm/s, P<0.05). In the CHF
      group, LV myocyte velocity of shortening was reduced by 45% compared to controls
      with no regional variation. beta-adrenergic stimulation increased myocyte
      velocity in both the control and CHF groups, however, regional variation was
      observed only in the CHF group. These unique results demonstrated that minimal
      regional variations in myocyte contractile function exist in both control and
      congestive heart failure states, and does not necessarily parallel patterns of
      regional LV end systolic wall stress.

PMID- 9236148
TI  - Angiotensin II stimulated expression of transforming growth factor-beta1 in
      cardiac fibroblasts and myofibroblasts.
AB  - Angiotensin II (Ang II) stimulates pathologic myocardial fibrosis. Cardiac
      fibroblasts (CFb) and myofibroblasts mediate this response, perhaps in part by
      indirect production of specific cytokines. We sought to determine if Ang II could
      stimulate transforming growth factor-beta1 (TGF-beta1) gene expression and
      protein production in adult rat CFb and two cardiac myofibroblast cell types,
      scar myofibroblasts (MyoFb) and valvular interstitial cells (VIC). Confluent CFb,
      MyoFb, and VIC in serum-deprived (0.4% FCS) media were treated with Ang II (10(
      7) m for CFb; 10(-9) m for MyoFb, VIC) for 24 h. Untreated cells served as
      controls. Culture media was collected and TGF-beta1 levels determined in
      triplicate using a sandwich ELISA. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis was performed to determine TGF-beta1 mRNA expression.
      Ang II increased CFb (P<0.02) and VIC (P<0.04) TGF-beta1 mRNA expression, while
      the increase in MyoFb was not statistically significant. MyoFb produced the
      highest TGF-beta1 levels under control conditions compared to VIC and CFb. Ang II
      stimulated further TGF-beta1 secretion in VIC and CFb, but not MyoFb. The AT1
      receptor antagonist Losartan (10(-7) m) greatly attenuated Ang II-stimulated TGF
      B1 secretion and decreased TGF-beta1 immunostaining in VIC. The AT2 receptor
      antagonist PD123177 (10(-7) m) also decreased secretion and immunostaining of TGF
      beta1 in VIC, but to a lesser extent than Losartan. TGF-beta1 secretion by MyoFb
      was unaffected by Losartan and PD123177, although TGF-B1 immunostaining was
      absent or greatly decreased, respectively, compared to Ang II-treated MyoFb. Ang
      II stimulates TGF-beta1 gene expression and/or protein production in cardiac
      fibroblast-like cells which may act as an autocrine/paracrine stimulus to
      collagen formation. Furthermore, TGF-beta1 production and secretion in these
      cells can be modulated by specific Ang II receptor antagonists, suggesting a
      potential benefit in preventing/attenuating pathologic myocardial fibrosis.

PMID- 9236149
TI  - Regulation of expression of the [3H]-dofetilide binding site associated with the
      delayed rectifier K+ channel by dexamethasone in neonatal mouse ventricle.
AB  - Developmental shortening of cardiac action potential duration in mouse appears to
      result, at least in part, from replacement of the rapid component of the delayed
      rectifying potassium current (IKr) with the transient outward current (ItO1).
      This developmental decrease in the IKr current density was paralleled by a loss
      of the high affinity [3H]-dofetilide binding site and loss of prolongation of
      action potential duration by dofetilide. Since glucocorticoid treatment prevented
      the developmental shortening of action potential duration in rats in the
      perinatal period, we hypothesized that chronic dexamethasone treatment would
      alter the developmental loss of IKr channel expression in mice. Accordingly, 10
      day-old mice were randomly allocated to chronic in vivo dexamethasone treatment
      (1 mg/kg) or placebo treatment for 3-5 days. At 15 days of life, transmembrane
      action potentials were recorded in right ventricular endocardium and [3H]
      dofetilide equilibrium binding studies were performed. The baseline action
      potential duration in the dexamethasone-treated animals was significantly greater
      than that in the control group (66+/-3 v 54+/-10 ms, respectively; P<0.01).
      Moreover, dofetilide significantly prolonged action potential duration in the
      dexamethasone-treated animals, but had no effect on the placebo-treated group
      (P<0.01). In addition, a high affinity [3H]-dofetilide binding site (Kd 96+/-21
      nM and Bmax 69+/-13 fmoles/mg protein) was observed in the dexamethasone-treated
      group (n=5), whereas no specific [3H]-dofetilide binding was observed in the
      placebo-treated group. In conclusion, dexamethasone modulates developmental
      regulation of IKr channel expression in mouse ventricle.

PMID- 9236150
TI  - Attenuation of myocardial ischaemic injury 24 h after diacylglycerol treatment in
      vivo.
AB  - Previous work suggests that delayed protection against infarction following
      ischaemic preconditioning of rabbit myocardium may involve the activation of
      protein kinase C (PKC). Preconditioning in the presence of chelerythrine, an
      inhibitor of PKC, abolished the late anti-infarct effect of preconditioning. In
      the studies described here, we tested the hypothesis that direct PKC activation
      with an analogue of diacylglycerol, the physiological activator of PKC, would
      invoke an adaptive mechanism leading to enhanced myocardial tolerance to
      ischaemia 24 h later. Rabbits were treated with i.v. injections of 1,2-dioctanoyl
      sn-glycerol (DiC8) 5 mg/kg or 15 mg/kg or an equivalent volume of vehicle
      solution. Twenty-four h after pretreatment, the animals were anaesthetised and
      underwent 30 min coronary artery occlusion with 120 min reperfusion. Infarct size
      was determined by triphenyltetrazolium staining. In vehicle pretreated rabbits,
      infarct-risk zone ratio was 32.8+/-2.6%. Pretreatment with DiC8 5 mg/kg did not
      significantly affect infarct size (26.3+/-4.0%), but pretreatment with DiC8 15
      mg/kg resulted in a marked reduction in infarct size (18.0+/-3.4%, P<0.05, 1-way
      ANOVA). Reduction in infarct size with the higher dose of DiC8 was independent of
      myocardial risk zone size and systemic haemodynamic parameters during coronary
      occlusion. The haemodynamic effects of acute administration of DiC8 15 mg/kg were
      examined in a separate cohort of pentobarbitone-anaesthetised rabbits. The
      compound was found not to affect systolic blood pressure or heart rate under
      these conditions. We examined the possibility that increased ischaemic tolerance
      might be due to induction of the 27 and 72 kDa heat shock proteins (hsp27 and
      hsp70i) which are known to be cytoprotective and are upregulated by ischaemia and
      other stressful stimuli. Western blot analysis of left ventricular tissue
      revealed that neither protein was induced 24 h after treatment with DiC8 15
      mg/kg. Thus, infarct limitation 24 h after DiC8 treatment did not appear to be
      due to increased tissue content of these proteins. The mechanisms of DiC8-induced
      delayed myocardial protection remain unclear. However, these data are compatible
      with the hypothesis that activation of PKC isoenzymes is an important
      intermediate signal of sub-acute cellular adaptation, and results in enhanced
      tolerance to ischaemia-reperfusion injury in myocardium many hours later.

PMID- 9236151
TI  - Delayed cardiac protection against harmful consequences of stress can be induced
      in experimental atherosclerosis in rabbits.
AB  - Multiple brief periods of rapid ventricular pacing confer both short- and long
      term protection on the ischaemic heart. The duration of the short-term protection
      does not exceed 2 h, whereas the long-term protective effect appears several
      hours after the inducing insults, with maximal protection 24-48 h later. Up to
      now, delayed cardiac protection by preceding ischaemic insults against harmful
      consequences of stress has been produced in the normal, healthy animal only. The
      purpose of this study was, therefore, to test whether delayed cardiac protection
      can be induced in experimental atherosclerosis in rabbits produced by feeding
      cholesterol-rich diet over 2 months. Repeated brief periods of rapid ventricular
      pacing were used to induce delayed protection of the heart. Moderation of post
      pacing right intracavitary ST segment elevation and that of the left ventricular
      end-diastolic pressure (both produced by ventricular overpacing: 500 beats/min
      for 15 min) were found in normal animals as well as in those fed cholesterol
      enriched diet. The short-lived protection induced by a single 'preconditioning'
      pacing was reproducible only in normal animals. As measured by means of
      radioimmunoassay, the protective effect of either short- or long-term protection
      appeared in parallel with an attenuation of ischaemia-induced increase in cardiac
      cyclic AMP content, in both normal and atherosclerotic rabbits. An increase in
      cardiac cyclic GMP content was characteristic of the short- but not long-term
      protection. These results suggest that the delayed cardiac protection by
      preceding multiple brief rapid pacings operates even in experimental
      atherosclerosis, but the short-term protection induced by a single
      preconditioning stimulus is lost.

PMID- 9236152
TI  - Depyrogenation of digestive enzymes reduces lipopolysaccharide tolerance in
      isolated cardiac myocytes.
AB  - The isolated myocyte is useful for examining the direct cardiac effects of
      substances such as lipopolysaccharide (LPS) and cytokines. However, the digestive
      enzymes used for standard cell isolation procedures are contaminated by several
      hundred ng/ml LPS. We depyrogenated the digestive enzymes with a series of Triton
      X-114 and Polymyxin B washes to remove 99.7-99.9% of the LPS. This lowered LPS
      contamination levels from 100-300 ng/ml to 0.15-0.70 ng/ml, while maintaining
      good quality cell isolations from the left ventricle of New Zealand white
      rabbits. We evaluated whether brief exposure to LPS contaminant levels, as occur
      during standard cell isolations, induces LPS tolerance. Cardiac myocytes
      (isolated with depyrogenated enzymes) were pre-exposed to 100 ng/ml LPS for 1 h,
      washed, then exposed to a challenge dose with 100 ng/ml LPS. The LPS challenge
      dose induced a time-dependent decrease in cell shortening over 6 h in myocytes
      without pre-exposure, but not in myocytes pre-exposed to an earlier dose of LPS.
      We examined whether LPS tolerance develops in myocytes isolated with untreated
      enzymes, compared with depyrogenated enzymes. In myocytes isolated with untreated
      enzymes, there was a significant decrease in cell shortening after 6 h exposure
      to 1000-10 000 ng/ml LPS. In myocytes isolated with depyrogenated enzymes, it
      required only 5-50 ng/ml LPS to induce a comparable cardiac depression. We
      conclude that brief exposure to LPS contaminant levels, which occur with standard
      cell isolation procedures, induces a hyporesponsiveness or tolerance to
      subsequent doses of LPS in isolated cardiac myocytes.

PMID- 9236153
TI  - Developmental expression of thrombin in zebrafish embryos: a novel model to study
      hemostasis.
AB  - A partial cDNA encoding zebrafish prothrombin has been cloned and used as a probe
      to study the temporal expression of prothrombin mRNA during early embryonic
      development. The results revealed accumulation of prothrombin mRNA in diverse
      tissues such as the eyes and myotomes in early embryogenesis. We have also
      examined the enzymatic activity of thrombin in converting fibrinogen to fibrin in
      individual embryos at different stages of development. We found that the fibrin
      forming activity does not temporally correlate with the first presence of
      thrombin mRNA in the early stages of embryogenesis, but does correlate with the
      initiation of blood formation. Our ability to observe the fibrin-forming activity
      in single individual embryo will facilitate studies on identifying recessive
      mutations affecting blood coagulation, such as the regulatory gene mutations
      controlling the clotting factor genes. Furthermore, the observation of thrombin
      activity will also facilitate studies on the blood coagulation pathways in the
      early embryogenesis in this zebrafish model.

PMID- 9236154
TI  - Rescue from lethal irradiation correlates with transplantation of 10-20 CFU-S-day
      12.
AB  - Repopulation by donor cells of a bone marrow ablated by irradiation is now
      recognized to proceed in two phases: initial repopulation that may be temporary
      followed by permanent engraftment of longterm repopulating cells (LTRC). While a
      single LTRC has been shown to be capable of restoring the entire lymph
      hemopoietic system of an irradiated animal, the identity of the temporary
      repopulating cells has not been established unequivocally. We used the results of
      transplantation of subpopulations successively enriched for LTRC and containing
      varying numbers of CFU-S-12 (colony-forming units in the spleen at day 12 post
      transplantation) and progenitors to determine the likely cell type and number of
      cells needed for initial survival after radiation. Subpopulations from untreated
      and 5-fluorouracil-treated mice were discriminated on the basis of antibody
      reactivity, Hoechst 33342 and rhodamine 123 fluorescence intensity and light
      scattering properties. The minimum rescue inocula varied greatly in CFU-GEMM, BFU
      E and CFU-GM content. One to two CFU-S-12 were uniformly present in all isolated
      suspensions that rescued 50% of lethally irradiated animals. In view of the known
      average seeding efficiency of CFU-S, our studies suggest that transfusion of 10
      20 CFU-S day 12/13 is responsible for radioprotection. Evidence that multiple CFU
      S day 12/13 are needed for initial repopulation is also supported by quantitative
      estimates of the number of mature cells that can be produced by CFU-S.
      Transfusion of a single CFU-S day 12/13 can be shown to be grossly inadequate to
      provide the number of peripheral blood cells needed to ameliorate the severe
      pancytopenia following lethal irradiation by day 12-14. Our data also indicate
      that 5-fluorouracil-treated marrow subpopulations appear inferior to untreated
      subpopulations in their ability to contribute to initial repopulation when
      transfused at low cell doses into lethally irradiated recipients.

PMID- 9236155
TI  - Co-transactivation of the 3' erythropoietin hypoxia inducible enhancer by the HIF
      1 protein.
AB  - Erythropoietin (Epo) is a glycoprotein hormone that is the primary regulator of
      red blood cell production. Epo production increases in response to tissue
      hypoxia. This increase occurs primarily at the transcriptional level. Hypoxia
      inducible factor (HIF-1) is a DNA binding protein that binds to a hypoxia
      inducible enhancer in the 3' flanking sequence of the Epo gene. HIF-1 is a
      heterodimer that consists of an alpha and beta subunit. HIF-1 DNA binding
      activity is induced in response to hypoxia. In order to determine if one or both
      HIF-1 subunits is capable of ligand binding, subsequently leading to Epo
      production we performed co-transactivation experiments. Transfections were
      performed in Hep 3B, an Epo producing human hepatoma cell line and Cos-7, a non
      Epo producing monkey kidney cell line. Cells were co-transfected with the 38 bp
      Epo enhancer fragment bearing the HIF-1 binding motif, subcloned in the
      luciferase reporter plasmid and either the HIF-1alpha cDNA, HIF-1beta cDNA, HIF
      1alpha and HIF-1beta cDNAs or pREP-4 respectively. Cells were incubated in an
      hypoxic (1%O2) or normoxic (21%O2) environment and assayed for luciferase
      activity. Epo levels were measured in the culture media from the transfected
      plates by an ELISA assay. Under hypoxic conditions Hep 3B cells transfected with
      the HIF-1alpha cDNA alone showed a 2.2 fold increase in luciferase activity, HIF
      1beta showed a 3.4 fold increase and cells transfected with HIF-1 alpha and beta
      showed a 6. 9 fold increase in activity over cells transfected with pREP-4. The
      baseline luciferase activity in transfected 3B cells incubated in normoxia was
      very low. However, a similar fold increase in luciferase activity in cells
      transfected with both HIF-1alpha and beta was noted. Under normoxic or hypoxic
      conditions in Cos-7 cells, a 1.5 fold increase was obtained with the HIF-1alpha
      and beta constructs transfected independently and a 3.5 fold increase was noted
      in cells transfected with both constructs. Epo levels increased several fold in
      all Hep 3B cells that were incubated in hypoxic conditions. However, there was no
      additional increase in Epo levels in transfected Hep 3B cells. We therefore
      conclude that although the HIF-1alpha and beta subunits can independently co
      transactivate the Epo enhancer, binding of both subunits and a hypoxic
      environment is necessary for maximal transactivation. Overexpression of the HIF-1
      protein alone in normoxic or hypoxic conditions is insufficient for an increase
      in Epo secretion. Activation/inactivation and interaction of other tissue
      specific factors is necessary for an increase in Epo gene expression in response
      to hypoxia.

PMID- 9236156
TI  - The effects of pyrroloquinoline quinone on heme-regulated eIF-2alpha kinase and
      eIF-2B activities in eukaryotic protein synthesis.
AB  - Pyrroloquinoline quinone (PQQ), a novel cofactor of biological redox processes,
      is ubiquitous in animal cells. We have examined the effects of PQQ on protein
      synthesis. PQQ inhibits protein synthesis in hemin-supplemented rabbit
      reticulocyte lysates. This inhibition is characterized by increased
      phosphorylation of eIF-2alpha and by diminished guanine nucleotide exchange
      activity of eIF-2B. The increased eIF-2alpha phosphorylation is the result of
      activation by PQQ of the heme-regulated eIF-2alpha kinase (HRI). The addition of
      10 microM PQQ completely inhibits the increase in protein synthesis that occurs
      on the addition of hemin (20 microM) to heme-deficient lysates, whereas a lower
      concentration of PQQ (100 nM) causes a very slight stimulation of protein
      synthesis. The increased eIF-2alpha phosphorylation that occurs at high
      concentrations of PQQ inhibits eIF-2B activity, presumably due to formation of a
      15S complex [eIF-2(alphaP).eIF-2B] in which eIF-2B becomes non-functional. Low
      concentrations of PQQ (0.1-1 microM) do not affect eIF-2alpha phosphorylation,
      but rather enhance the guanine nucleotide exchange activity of eIF-2B in
      reticulocyte lysates. In Chinese hamster ovary cell extract which is devoid of
      significant eIF-2alpha kinase activity, addition of both low and high
      concentrations of PQQ results in an increase in eIF-2B activity. The addition of
      PQQ to reticulocyte lysates activates HRI whereas addition of PQQ to purified HRI
      in vitro inhibits the autokinase and eIF-2alpha kinase activity of the HRI; the
      inhibition of purified HRI by PQQ is observed both in the presence and absence of
      hemin. These findings suggest that PQQ inhibits purified HRI by acting as an
      oxidant whereas in lysates in which PQQ is readily reduced, the PQQ acts as a
      reductant and increases the activities of both HRI and eIF-2B.

PMID- 9236158
TI  - Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease.
AB  - In type 1 Gaucher disease, decreased activity of glucocerebrosidase results in
      accumulation of glucosylceramide in macrophages. Infiltration of liver, spleen
      and bone marrow by lipid-laden macrophages leads to hepatosplenomegaly, bone
      lesions and cytopenia. These abnormal macrophages may produce and release
      macrophage derived factors and cytokines, which could contribute to the
      pathophysiology of the disease. Whether these cytokines and factors are elevated
      in Gaucher disease is currently unknown. In 29 type 1 Gaucher disease patients we
      measured serum levels of the macrophage derived cytokines IL8, IL6, TNFalpha, M
      CSF and the monocyte/macrophage activation marker sCD14. These factors were
      studied in relation to disease severity and during treatment with enzyme
      supplementation therapy. Most patients showed remarkably elevated levels of M-CSF
      (2-8 fold) and sCD14 (2-5 fold) as compared to normal controls. Levels of IL8
      were elevated in all patients (2-20 fold), whereas levels of IL6 and TNFalpha
      were normal. There was a significant correlation between severity of the disease
      as determined by the severity score index (SSI), and M-CSF, sCD14 and IL8 levels.
      M-CSF and sCD14 levels also correlated with the excess liver and spleen volumes.
      During treatment with alglucerase, levels of M-CSF and sCD14 declined, but IL8
      remained unchanged. The relative reduction in excess liver and spleen volume did
      not correlate with the relative reduction in M-CSF or sCD14 levels. We conclude
      that serum levels of M-CSF, sCD14 and IL8 are increased in type 1 Gaucher
      disease. The biological activities of M-CSF and IL8 may add to the
      pathophysiology of the disease.

PMID- 9236157
TI  - Fetal hemoglobin in sickle cell anemia: examination of phylogenetically conserved
      sequences within the locus control region but outside the cores of hypersensitive
      sites 2 and 3.
AB  - Regulatory elements linked to the beta-globin gene cluster modulates gamma-globin
      gene expression. The location of all of these elements and their mechanisms of
      action are still incompletely defined. Phylogenetically conserved DNA within the
      beta-globin gene cluster locus control region (LCR), but outside the core
      sequences of its hypersensitive sites (HS), were identified and we searched for
      any differences between HS 3 and HS 2, and HS 2 and HS 1, among patients with
      sickle cell anemia with different levels of Hb F who were homozygous for the
      common haplotypes. DNA was amplified with and without GC clamps, digested with
      restriction endonucleases, and examined by denaturing gradient gel
      electrophoresis (DGGE). We found limited fragment size diversity. However, the
      type of differences found and their distribution among haplotypes did not suggest
      that they represented distinctive changes that might explain the differential
      expression of the gamma-globin genes in sickle cell anemia.

PMID- 9236159
TI  - The evidence of clonal evolution with monosomy 7 in aplastic anemia following
      granulocyte colony-stimulating factor using the polymerase chain reaction.
AB  - We present here the case of a Japanese female patient with aplastic anemia who
      developed monosomy 7 and clonal evolution following a treatment with recombinant
      human granulocyte colony-stimulating factor (rhG-CSF). At the onset of aplastic
      anemia, cytogenetic analysis was 46, XX and X-inactivation/methylation analysis
      revealed a polyclonal pattern. After 4 months of administration of rhG-CSF, she
      had 45, XX, -7 and a clonal pattern, although there were no morphological
      evidence of a myelodysplastic syndrome or leukemia. The ratio of monosomy 7 to
      normal analyzed by fluorescence in situ hybridization decreased after
      discontinuation of rhG-CSF and there were still no dysplastic changes and/or
      increased numbers of blasts. These results indicate that the acquisition of
      monosomy 7 following rhG-CSF treatment dose not always cause clonal evolution to
      induce hematological malignancies.

PMID- 9236161
TI  - Protected Values
AB  - Protected values are those that resist trade-offs with other values, particularly
      economic values. We propose that such values arise from deontological rules
      concerning action. People are concerned about their participation in transactions
      rather than just with the consequences that result. This proposal implies that
      protected values, defined as those that display trade-off resistance, will also
      tend to display quantity insensitivity, agent relativity, and moral obligation.
      People will also tend to experience anger at the thought of making trade-offs,
      and to engage in denial of the need for trade-offs through wishful thinking.
      These five properties were correlated with tradeoff resistance (across different
      values, within subjects) in five studies in which subjects answered several
      questions about each of several values, or in which they indicated their
      willingness to pay to prevent some harmful action. These correlations were found
      even when the subjects could not tell the experimenters which values they were
      responding to, so they cannot be ascribed entirely to subjects' desire to express
      commitment. We discuss implications for value measurement and public policy.

PMID- 9236162
TI  - The Effects of Social Identity on the Self-Set Goals and Task Performance of High
      and Low Self-Esteem Individuals
AB  - Social identification with co-workers was examined as a moderator of the
      frequently inscrutable link between worker self-esteem and goal setting. Weak or
      strong social identity was created in groups comprised of either high or low self
      esteem persons. As expected, strengthening social identity increased perceived
      similarity to ingroup members regardless of self-esteem. Furthermore, only high
      self-esteem individuals with a strong social identity set higher goals for
      themselves, and achieved better performance, compared to high esteem/weak
      identity individuals or low self-esteem persons in either social identity
      condition. Increments in the goals and performance of high self-esteem
      individuals were associated with perceived similarity to ingroup members, and
      performance was attributed to personal ability. In contrast, the goals and
      performance of low self-esteem individuals were associated with certainty of goal
      achievement, and performance was attributed to perceptions of task difficulty.
      Asymmetrical effects of social identification are discussed in relation to group
      member personalities.

PMID- 9236163
TI  - Effects of Judgment on Memory: Experiments in Recognition Bias and Process
      Dissociation in a Professional Judgment Task
AB  - Three experiments investigated post-judgment memory bias in a professional task
      for which the judge is liable. The experimental setting replicates a task in
      which a subordinate documents evidence after making a judgment, and a reviewer
      affirms or overrules the judgment from evidence the subordinate documents. This
      setting is common, for example, in auditing firms, law firms, and investment
      banking houses. The results lead to three findings. First, subordinates'
      judgments interact with evidence in memory to bias their post-judgment
      recognition of the evidence they will document in evidence files. Second,
      subordinate memory performance is consistent with the predictions of process
      dissociation: Conscious recollection is lower when attention is divided, but
      unconscious familiarity is invariant to attention manipulations. Third, the
      incomplete evidence sets that subordinates recognize and document systematically
      bias reviewers' judgments in the direction of subordinates' judgments.

PMID- 9236164
TI  - Looking and Weighting in Judgment and Choice
AB  - A sampling model was proposed in which the weight given to a piece of information
      corresponds to the amount of sampling of that information in either a continuous,
      discrete or strategic manner. These three sampling processes were related to
      process tracing measures of initial and additional time per acquisition and
      frequency of acquisition. The applicability of the sampling model was tested in
      three experiments in which students uncovered information corresponding to verbal
      and math aptitude scores of hypothetical applicants and either judged the
      likelihood of success in a designated major or chose which of a pair of
      applicants was more likely to succeed in the major. Task focus was manipulated by
      altering the designated major. In Experiment 1, analysis of judgment data
      demonstrated large effects of task focus on the weighting of verbal and math
      scores and corresponding increases in number of acquisitions and time per
      acquisition on the information receiving more weight. In Experiments 2 and 3,
      analyses of choice proportions revealed effects of task focus on weight and bias
      parameters. Looking data in choice provided strong support for two of the stages
      of processing described by Russo and Leclerc (1994). Initial looks reflected
      orientation and screening functions and additional looks reflected more
      evaluative processes. Experiment 3 also explored similarities and differences
      among groups of participants who were classified as following different
      identifiable choice strategies.

PMID- 9236165
TI  - Judging Relative Importance: Direct Rating and Point Allocation Are Not
      Equivalent
AB  - In this series of experiments we investigate two commonly used methods of
      assigning numerical values (i.e., decision weights) to attributes in order to
      signify their perceived relative importance. The two methods are to ask people to
      directly rate each of the attributes in turn (Rating), or to allocate a budget of
      points (typically 100 points) to the attributes (Point Allocation or PA). These
      procedures may seem to be minor variants of one another, yet they produce very
      different profiles of decision weights. The differences are predicted by a
      simple, idealized model of weighting, from which Rating and PA, in different
      ways, exhibit consistent elicitation-dependent bias.

PMID- 9236166
TI  - Regret and Responsibility in the Evaluation of Decision Outcomes
AB  - The negative affect associated with bad decision outcomes is often thought to
      involve feelings of remorse or self-blame. For example, studies showing greater
      regret associated with active than with passive choice are interpreted as the
      active chooser piling self-recrimination on top the disappointment of a poor
      outcome. Corresponding rejoicing is postulated for active choice that leads to
      good outcomes. The five experiments reported here challenge such a view. In each,
      hypothetical individuals experienced identical gains or losses, some as a result
      of their own choice, others as a result of an external, arbitrary process. Though
      evaluations of final outcomes were heavily influenced by the paths by which the
      outcomes were reached, and by the comparison levels that were evoked, in no case
      was decision agency a significant influence. In these experiments, then, the
      "active chooser" effect appears more a matter of change than of choice, of the
      route taken rather than whether one is the driver or the passenger. Further
      research will be needed to establish the circumstances under which different
      salient comparisons are evoked.

PMID- 9236184
TI  - Natural immunity against human immunodeficiency viruses: prospects for AIDS
      vaccines.
AB  - We have hypothesized and have presented evidence that there may be another form
      of immunity, other than humoral and cellular immunities, which operates against
      retroviruses. In order to distinguish it from the traditional immune responses,
      we have named this form of immunity "molecular immunity". The major goal of this
      hypothesis is to better define the "messenger molecules" that are critical in
      forming the molecular immunity against retroviruses, and to further determine the
      activation pathways of this relatively unexplored form of immunity. We have
      provided evidence that this natural immunity against retroviruses and
      specifically against HIV-1, can be activated and optimized, and have made some
      interesting observations. We believe that resistance to HIV-1 and to other
      retroviruses can be induced by various means, including low dose exposure,
      infection with replication defective viruses and exposure to non-pathogenic but
      genetically related viruses.

PMID- 9236185
TI  - Migration and activation pattern of specialized dendritic cells after heterotopic
      small bowel transplantation in a graft-versus-host model of the rat.
AB  - Besides specific cellular-mediated T cell responses, B cell related humoral
      responses have been demonstrated during the course of graft-versus-host disease
      after semiallogeneic transplantation of cellular antigen. Following
      semiallogeneic small bowel transplantation, there are, besides others, two
      specific forms of antigen-presenting cells, namely sinus lining cells (SLCs) and
      follicular dendritic cells (FDCs) which mediate primary and secondary humoral
      immune responses, respectively. This study was aimed to clarify the role of these
      dendritic cell entities after transplantation of small bowel grafts in a one
      sided graft-versus-host (GvH) model for untreated and immunosuppressed (15
      deoxyspergualin) recipient animals. As graft-versus-host disease progressed, SLCs
      and FDCs were eliminated in donor and recipient graft-versus-host associated
      target tissues (spleen and mesenteric lymph nodes) of untreated animals, whereas
      these dendritic cells prevailed in immunosuppressed recipients. 15
      deoxyspergualin successfully prevented GvHD and significantly prolonged the mean
      survival time of untreated rats (16.0 +/- 4.5 d) for at least 21 d. Based on the
      immunosuppressive efficacy of 15-deoxyspergualin on the survival and function of
      SLCs and FDCs, an unaltered development of germinal centers and B cell
      proliferation within mesenteric lymph nodes and spleen was maintained

PMID- 9236186
TI  - Specificity in the cAMP/PKA signaling pathway. differential expression,
      regulation, and subcellular localization of subunits of PKA.
AB  - A large number of hormones, neurotransmitters and other signal substances utilize
      cyclic adenosine 3 5  cyclic monophosphate (cAMP) as an intracellular second
      messenger. Cyclic AMP regulates a number of different cellular processes such as
      cell growth and differentiation, ion channel conductivity, synaptic release of
      neurotransmitters, and gene transcription The principle intracellular target for
      cAMP in mammalian cells is the cAMP-dependent protein kinase (PKA). The fact that
      this broad specificity protein kinase mediates a number of discrete physiological
      responses following cAMP engagement, has raised the question of how specificity
      is maintained in the cAMP/PKA system. Here, we will describe features of PKA
      signaling pathway that may contribute to explain how differential effects of cAMP
      may be maintained in this pathway.

PMID- 9236188
TI  - Clinical and serologic manifestations of autoimmune disease in MRL-lpr/lpr mice
      lacking nitric oxide synthase type 2.
AB  - Nitric oxide (NO) is an important mediator of the inflammatory response. MRL
      lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce
      NO in parallel with the development of an autoimmune syndrome with a variety of
      inflammatory manifestations. In previous studies, we showed that inhibiting NO
      production with the nonselective nitric oxide synthase (NOS) inhibitor NG
      monomethyl-arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL
      lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL-lpr/lpr
      mice, mice with targeted disruption of NOS2 were produced by homologous
      recombination and bred to MRL-lpr/lpr mice to the N4 generation. MRL-lpr/lpr
      littermates homozygous for disrupted NOS2 (-/-), heterozygous for disrupted NOS2
      (+/-), or wildtype (+/+) were derived for this study. Measures of NO production
      were markedly decreased in the MRL-lpr/lpr (-/-) mice compared with MRL-lpr/lpr
      (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/-) mice. There was
      no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney,
      and peritoneal macrophages of the (-/-) animals, whereas that of (+/+) was high
      and (+/-) intermediate. The (-/-) mice developed glomerular and synovial
      pathology similar to that of the (+/-) and (+/+) mice. However, (-/-) mice and
      (+/-) mice had significantly less vasculitis of medium-sized renal vessels than
      (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (-/-)
      mice as compared with (+/+) mice, but levels of anti-DNA antibodies were
      comparable in all groups. Our findings show that NO derived from NOS2 has a
      variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting
      heterogeneity in disease mechanisms.

PMID- 9236187
TI  - Natural killer cell tolerance in mice with mosaic expression of major
      histocompatibility complex class I transgene.
AB  - We have studied natural killer (NK) cell tolerance in a major histocompatibility
      complex (MHC) class I transgenic line, DL6, in which the transgene product was
      expressed on only a fraction of blood cells. In contrast with transgenic mice
      expressing the same transgene in all cells, NK cells from mosaic mice failed to
      reject transgene-negative bone marrow or lymphoma grafts. However, they retained
      the capability to reject cells with a total missing-self phenotype, i.e., cells
      lacking also wild-type MHC class I molecules. Tolerance against transgene
      negative cells was demonstrated also in vitro, and could be broken if transgene
      positive spleen cells of mosaic mice were separated from negative cells before,
      or after 4 d of culture in interleukin-2. The results provide support for
      selective NK cell tolerance to one particular missing-self phenotype but not to
      another. We suggest that this tolerance is determined by NK cell interactions
      with multiple cells in the environment, and that it is dominantly controlled by
      the presence of cells lacking a specific MHC class I ligand. Furthermore, the
      tolerant NK cells could be reactivated in vitro, which suggests that the
      tolerance occurs without deletion of the potentially autoreactive NK cell
      subset(s), and that it may be dependent upon the continuous presence of
      tolerizing cells.

PMID- 9236189
TI  - The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode
      of action.
AB  - Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen
      that stimulates Vbeta2-bearing human T cells, but is inactive in mice. SPE-C
      binds with high affinity to both human HLA-DR and murine I-E molecules, but not
      to murine I-A molecules in a zinc-dependent fashion. Competition binding studies
      with other recombinant toxins revealed that SPE-C lacks the generic low affinity
      major histocompatibility complex (MHC) class II alpha-chain binding site common
      to all other bacterial superantigens. Despite this, SPE-C cross-links MHC class
      II to induce homotypic aggregation of class II-bearing B cells. Nondenaturing
      sodium dodecyl sulfate electrophoresis and size exclusion chromatography revealed
      that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or
      alkaline pH. These data support a recent crystal structure of SPE-C and reveal
      yet another mechanism by which bacterial superantigens ligate and cross-link MHC
      class II.

PMID- 9236190
TI  - Interferon gamma (IFN-gamma) is necessary for the genesis of acetylcholine
      receptor-induced clinical experimental autoimmune myasthenia gravis in mice.
AB  - Experimental autoimmune myasthenia gravis (EAMG) is an animal model of human
      myasthenia gravis (MG). In mice, EAMG is induced by immunization with Torpedo
      californica acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA).
      However, the role of cytokines in the pathogenesis of EAMG is not clear. Because
      EAMG is an antibody-mediated disease, it is of the prevailing notion that Th2 but
      not Th1 cytokines play a role in the pathogenesis of this disease. To test the
      hypothesis that the Th1 cytokine, interferon (IFN)-gamma, plays a role in the
      development of EAMG, we immunized IFN-gamma knockout (IFN-gko) (-/-) mice and
      wild-type (WT) (+/+) mice of H-2(b) haplotype with AChR in CFA. We observed that
      AChR-primed lymph node cells from IFN-gko mice proliferated normally to AChR and
      to its dominant pathogenic alpha146-162 sequence when compared with these cells
      from the WT mice. However, the IFN-gko mice had no signs of muscle weakness and
      remained resistant to clinical EAMG at a time when the WT mice exhibited severe
      muscle weakness and some died. The resistance of IFN-gko mice was associated with
      greatly reduced levels of circulating anti-AChR antibody levels compared with
      those in the WT mice. Comparatively, immune sera from IFN-gko mice showed a
      dramatic reduction in mouse AChR-specific IgG1 and IgG2a antibodies. However,
      keyhole limpet hemocyanin (KLH)-priming of IFN-gko mice readily elicited both T
      cell and antibody responses, suggesting that IFN-gamma regulates the humoral
      immune response distinctly to self (AChR) versus foreign (KLH) antigens. We
      conclude that IFN-gamma is required for the generation of a pathogenic anti-AChR
      humoral immune response and for conferring susceptibility of mice to clinical
      EAMG.

PMID- 9236191
TI  - In vitro translation and assembly of a complete T cell receptor-CD3 complex.
AB  - The T cell receptor for antigen (TCR) is a multisubunit complex that consists of
      at least seven polypeptides: the clonotypic, disulfide-linked alpha/beta
      heterodimer that is noncovalently associated with the invariant polypeptides of
      the CD3 complex (CD3-gamma, -delta, -epsilon) and zeta, a disulfide-linked
      homodimer. We achieved the complete assembly of the human TCR in an in vitro
      transcription/translation system supplemented with dog pancreas microsomes by
      simultaneous translation of the messenger RNAs encoding the TCR-alpha, -beta and
      CD3-gamma, -delta, -epsilon, and -zeta subunits. CD3-epsilon, one of the subunits
      that initiates the assembly of the TCR in living cells, forms misfolded,
      disulfide-linked homooligomers when translated alone. However, co-translation of
      one of its first binding partners in the course of assembly, CD3-gamma or -delta,
      led to the expression of mainly monomeric and correctly folded epsilon subunits,
      the only form we could detect as part of a properly assembled TCR complex. In the
      absence of these subunits, the ER-resident chaperone calnexin interacted with
      oligomeric, i.e. misfolded, structures of CD3-epsilon in a glycan-independent
      manner. A glycan-dependent interaction between CD3-epsilon and calnexin was
      mediated by CD3-gamma and concerned only monomeric CD3-epsilon complexed with CD3
      gamma, but was dispensable for proper folding of CD3-epsilon. We suggest that in
      addition to its signaling function, CD3-epsilon serves as a monitor for proper
      subunit assembly of the TCR.

PMID- 9236193
TI  - B lymphocytes of xeroderma pigmentosum or Cockayne syndrome patients with
      inherited defects in nucleotide excision repair are fully capable of somatic
      hypermutation of immunoglobulin genes.
AB  - Recent experiments have strongly suggested that the process of somatic mutation
      is linked to transcription initiation. It was postulated that a mutator factor
      loads onto the RNA polymerase and, during elongation, causes transcriptional
      arrest that activates DNA repair, thus occasionally causing errors in the DNA
      sequence. We report the analysis of the role of one of the known DNA repair
      systems, nucleotide excision repair (NER), in somatic mutation. Epstein-Barrvirus
      transformed B cells from patients with defects in NER (XP-B, XP-D, XP-V, and CS
      A) were studied. Their heavy and light chain genes show a high frequency of point
      mutations in the variable (V), but not in the constant (C) regions. This suggests
      that these B cells can undergo somatic hypermutation despite significant defects
      in NER. Thus, it is doubtful that NER is an essential part of the mechanism of
      somatic hypermutation of Ig genes. As an aside, NER seems also not involved in Ig
      gene switch recombination.

PMID- 9236192
TI  - Two orphan seven-transmembrane segment receptors which are expressed in CD4
      positive cells support simian immunodeficiency virus infection.
AB  - Clinical isolates of primate immunodeficiency viruses, including human
      immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding
      to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane
      receptor family. HIV-1 variants which use additional chemokine receptors are
      present in the central nervous system or emerge during the course of infection.
      Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a
      coreceptor, but no other receptors for these viruses have been identified. Here
      we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15,
      serve as coreceptors for SIV, and are expressed in human alveolar macrophages.
      The more efficient of these, gpr15, is also expressed in human CD4(+) T
      lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The
      gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share
      with CCR5 an amino-terminal motif rich in tyrosine residues. These results
      underscore the potential diversity of seven-transmembrane segment receptors used
      as entry cofactors by primate immunodeficiency viruses, and may contribute to an
      understanding of viral variation and pathogenesis.

PMID- 9236194
TI  - Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine
      secretion and pulmonary eosinophilia during experimental murine respiratory
      syncytial virus infection.
AB  - T lymphocytes play a pivotal role in the immune response during viral infections.
      In a murine model of experimental respiratory syncytial virus (RSV) infection,
      mice sensitized to either of the two major glycoproteins of RSV develop distinct
      patterns of cytokine secretion and lung inflammation upon subsequent RSV
      infection. Mice sensitized to RSV-G (attachment) glycoprotein exhibit a strong
      interleukin (IL)-4 and IL-5 response and develop pulmonary eosinophilia, whereas
      mice sensitized to RSV-F (fusion) glycoprotein develop a predominantly T helper
      cell (Th)1 response and pulmonary inflammation characterized by mononuclear cell
      infiltration. In this study, we examined the potential role of virus-specific
      CD8+ T cytolytic T cells on the differentiation and activation of functionally
      distinct CD4+ T cells specific to these viral glycoproteins. Mice primed with
      recombinant vaccinia virus expressing RSV-F glycoprotein mounted a strong RSV
      specific, MHC class I-restricted cytolytic response, whereas priming with
      recombinant vaccinia virus expressing RSV-G glycoprotein failed to elicit any
      detectable cytolytic response. Priming for a RSV-specific CD8+ T cell response,
      either with a recombinant vaccinia virus expressing RSV-G glycoprotein in which a
      strong CD8+ T cell epitope from RSV-M2 (matrix) protein has been inserted or with
      a combination of vaccinia virus expressing the matrix protein and the RSV-G
      glycoprotein, suppressed the eosinophil recruitment into the lungs of these mice
      upon subsequent challenge with RSV. This reduction in pulmonary eosinophilia
      correlated with the suppression of Th2 type cytokine production. The importance
      of CD8+ T cells in this process was further supported by the results in CD8+ T
      cell deficient, beta 2 microglobulin KO mice. In these mice, priming to RSV-F
      glycoprotein (which in normal mice primed for a strong cytolytic response and a
      pulmonary infiltrate consisting primarily of mononuclear cells on RSV challenge)
      resulted in the development of marked pulmonary eosinophilia that was not seen in
      mice with an intact CD8+ T cell compartment. These results indicate that CD8+ T
      cells may play an important role in the regulation of the differentiation and
      activation of Th2 CD4+ T cells as well as the recruitment of eosinophils into the
      lungs during RSV infection.

PMID- 9236195
TI  - The gene for a T lymphocyte triggering factor from African trypanosomes.
AB  - An early and essential event in the protective immune response against most
      viruses and protozoa is the production of interferon-gamma (IFN-gamma). In
      contrast, during infection with African trypanosomes, protozoan parasites that
      cause human sleeping sickness, the increased levels of IFN-gamma do not correlate
      with a protective response. We showed previously that African trypanosomes
      express a protein called T lymphocyte triggering factor (TLTF), which triggers
      CD8(+) T lymphocytes to proliferate and to secrete IFN-gamma. Here, we isolate
      the gene for TLTF and demonstrate that the recombinant version of TLTF
      specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma.
      Studies with TLTF fused to the green fluorescent protein show that TLTF is
      localized to small vesicles that are found primarily at or near the flagellar
      pocket, the site of secretion in trypanosomes. TLTF is likely to be only the
      first example of a class of proteins that we designate as trypanokines, i.e.,
      factors secreted by trypanosomes that modulate the cytokine network of the host
      immune system for the benefit of the parasite.

PMID- 9236196
TI  - Disruption of the Bcl6 gene results in an impaired germinal center formation.
AB  - The Bcl6 gene has been identified from the chromosomal translocation breakpoint
      in B cell lymphomas, and its products are expressed highly in germinal center
      (GC) B cells. To investigate the function of Bcl6 in lymphocytes, we have
      generated RAG1-deficient mice reconstituted with bone marrow cells from Bcl6
      deficient mice (Bcl6(-/-)RM). Lymphogenesis in primary lymphoid tissues of Bcl6(
      /-)RM is normal, and Bcl6(-/-)RM produced control levels of primary IgG1
      antibodies specific to T cell-dependent antigens. However, GCs were not found in
      these mice. This defect was mainly due to the abnormalities of B cells.
      Therefore, Bcl6 is essential for the differentiation of GC B cells.

PMID- 9236197
TI  - Development of eosinophilic airway inflammation and airway hyperresponsiveness in
      mast cell-deficient mice.
AB  - Mast cells are the main effector cells of immediate hypersensitivity and
      anaphylaxis. Their role in the development of allergen-induced airway
      hyperresponsiveness (AHR) is controversial and based on indirect evidence. To
      address these issues, mast cell-deficient mice (W/W v) and their congenic
      littermates were sensitized to ovalbumin (OVA) by intraperitoneal injection and
      subsequently challenged with OVA via the airways. Comparison of OVA-specific
      immunoglobulin E (IgE) levels in the serum and numbers of eosinophils in
      bronchoalveolar lavage fluid or lung digests showed no differences between the
      two groups of mice. Further, measurements of airway resistance and dynamic
      compliance at baseline and after inhalation of methacholine were similar. These
      data indicate that mast cells or IgE-mast cell activation is not required for the
      development of eosinophilic inflammation and AHR in mice sensitized to allergen
      via the intraperitoneal route and challenged via the airways.

PMID- 9236198
TI  - Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4(+) T cells from
      exposed uninfected individuals expressing the wild-type CCR-5 allele.
AB  - Despite repeated exposure to HIV-1, certain individuals remain persistently
      uninfected. Such exposed uninfected (EU) people show evidence of HIV-1-specific T
      cell immunity and, in rare cases, selective resistance to infection by macrophage
      tropic strains of HIV-1. The latter has been associated with a 32-base pair
      deletion in the C-C chemokine receptor gene CCR-5, the major coreceptor of
      macrophage-tropic strains of HIV-1. We have undertaken an analysis of the HIV
      specific T cell responses in 12 EU individuals who were either homozygous for the
      wild-type CCR-5 allele or heterozygous for the deletion allele (CCR-5Delta32). We
      have found evidence of an oligoclonal T cell response mediated by helper T cells
      specific for a conserved region of the HIV-1 envelope. These cells produce very
      high levels of C-C chemokines when stimulated by the specific antigen and
      suppress selectively the replication of macrophage-tropic, but not T cell-tropic,
      strains of HIV-1. These chemokine-producing helper cells may be part of a
      protective immune response that could be potentially exploited for vaccine
      development.

PMID- 9236199
TI  - Influences of transporter associated with antigen processing (TAP) on the
      repertoire of peptides associated with the endoplasmic reticulum-resident stress
      protein gp96.
AB  - The endoplasmic reticulum (ER)-resident stress protein gp96 induces protective
      immunity and specific cytotoxic T lymphocyte (CTL) responses against antigens
      expressed in those cells it has been isolated from. This ability is based on
      peptides associated with gp96. Because gp96 is located inside the ER, our
      experiments address the question whether or not the repertoire of peptides
      associated with gp96 is influenced by the transporter associated with antigen
      processing (TAP). For this purpose, gp96 was isolated from cells with and without
      a TAP defect and used for immunization of mice. We found that for some antigens
      the association of peptides with gp96 required functional TAP molecules, whereas
      the association of peptides from other antigens was TAP independent. In the case
      of a TAP-dependent association of peptides with gp96, our results prove that
      peptide binding by gp96 in vivo occurs inside the ER and is not an artifact
      induced by cell lysis during the gp96 purification. The finding that some
      antigens can also associate with gp96 in the absence of functional TAP molecules
      indicates that the repertoire of peptides bound by gp96 truly reflects the entire
      repertoire of peptides present inside the ER and not only those peptides
      transported by TAP. These results, together with the earlier finding that the
      gp96 peptide repertoire is independent of the major histocompatibility complex
      molecules expressed by the cell gp96 is isolated from, give the theoretical
      foundation for the ability of gp96 to induce CTL responses against all kinds of
      intracellular antigens.

PMID- 9236200
TI  - Rat spleen dendritic cells express natural killer cell receptor protein 1 (NKR
      P1) and have cytotoxic activity to select targets via a Ca2+-dependent mechanism.
AB  - Dendritic cells (DC) are a subset of leukocytes whose major function is antigen
      presentation. We investigated the phenotype and function of enriched (95-98.5%)
      rat DC. We show that both spleen and thymus DC express the natural killer cell
      receptor protein 1 (NKR-P1) as a disulfide linked homodimer of 60 kD. Freshly
      isolated DC express a low level of NKR-P1, which is strongly upregulated after
      overnight culture. Spleen, but not thymus DC, were able to kill the NK-sensitive
      YAC-1 cell line in vitro, and since this killing was Ca2+ dependent, a Fas ligand
      Fas interaction was probably not involved. Besides their potent antigen
      presenting function, DC can thus be cytotoxic for some tumor targets.

PMID- 9236202
TI  - Single channel seeks permeant ion for brief but intimate relationship.

PMID- 9236201
TI  - Negative signaling pathways of the killer cell inhibitory receptor and Fc gamma
      RIIb1 require distinct phosphatases.
AB  - Inhibition of natural killer (NK) cells by the killer cell inhibitory receptor
      (KIR) involves recruitment of the tyrosine phosphatase SHP-1 by KIR and is
      prevented by expression of a dominant negative SHP-1 mutant. Another inhibitory
      receptor, the low affinity Fc receptor for immunoglobulin G (IgG) (Fc gamma
      RIIb1), has been shown to bind SHP-1 when cocross-linked with the antigen
      receptor on B cells (BCR). However, coligation of Fc gamma RIIb1 with BCR and
      with Fc epsilon RI on mast cells leads to recruitment of the inositol 5'
      phosphatase SHIP and to inhibition of mast cells from SHP-1-deficient mice. In
      this study, we evaluated the ability of these two inhibitory receptors to block
      target cell lysis by NK cells, and the contribution of SHP-1 and SHIP to
      inhibition. Recombinant vaccinia viruses encoding chimeric receptors and dominant
      negative mutants of SHP-1 and SHIP were used for expression in mouse and human NK
      cells. When the KIR cytoplasmic tail was replaced by that of Fc gamma RIIb1,
      recognition of HLA class I on target cells by the extracellular domain resulted
      in inhibition. A dominant negative mutant of SHP-1 reverted the inhibition
      mediated by the KIR cytoplasmic tail but not that mediated by Fc gamma RIIb1. In
      contrast, a dominant negative mutant of SHIP reverted only the inhibition
      mediated by the Fc gamma RIIb1 tail, providing functional evidence that SHIP
      plays a role in the Fc gamma RIIb1-mediated negative signal. These data
      demonstrate that inhibition of NK cells by KIR involves primarily the tyrosine
      phosphatase SHP-1, whereas inhibition mediated by Fc gamma RIIb1 requires the
      inositol phosphatase SHIP.

PMID- 9236203
TI  - Allosteric effects of permeating cations on gating currents during K+ channel
      deactivation.
AB  - K+ channel gating currents are usually measured in the absence of permeating
      ions, when a common feature of channel closing is a rising phase of off-gating
      current and slow subsequent decay. Current models of gating invoke a concerted
      rearrangement of subunits just before the open state to explain this very slow
      charge return from opening potentials. We have measured gating currents from the
      voltage-gated K+ channel, Kv1.5, highly overexpressed in human embryonic kidney
      cells. In the presence of permeating K+ or Cs+, we show, by comparison with data
      obtained in the absence of permeant ions, that there is a rapid return of charge
      after depolarizations. Measurement of off-gating currents on repolarization
      before and after K+ dialysis from cells allowed a comparison of off-gating
      current amplitudes and time course in the same cells. Parallel experiments
      utilizing the low permeability of Cs+ through Kv1.5 revealed similar rapid charge
      return during measurements of off-gating currents at ECs. Such effects could not
      be reproduced in a nonconducting mutant (W472F) of Kv1.5, in which, by
      definition, ion permeation was macroscopically absent. This preservation of a
      fast kinetic structure of off-gating currents on return from potentials at which
      channels open suggests an allosteric modulation by permeant cations. This may
      arise from a direct action on a slow step late in the activation pathway, or via
      a retardation in the rate of C-type inactivation. The activation energy barrier
      for K+ channel closing is reduced, which may be important during repetitive
      action potential spiking where ion channels characteristically undergo continuous
      cyclical activation and deactivation.

PMID- 9236204
TI  - Selectivity changes during activation of mutant Shaker potassium channels.
AB  - Mutations of the pore-region residue T442 in Shaker channels result in large
      effects on channel kinetics. We studied mutations at this position in the
      backgrounds of NH2-terminal-truncated Shaker H4 and a Shaker -NGK2 chimeric
      channel having high conductance (Lopez, G.A., Y.N. Jan, and L.Y. Jan. 1994.
      Nature (Lond.). 367: 179-182). While mutations of T442 to C, D, H, V, or Y
      resulted in undetectable expression in Xenopus oocytes, S and G mutants yielded
      functional channels having deactivation time constants and channel open times two
      to three orders of magnitude longer than those of the parental channel.
      Activation time courses at depolarized potentials were unaffected by the
      mutations, as were first-latency distributions in the T442S chimeric channel. The
      mutant channels show two subconductance levels, 37 and 70% of full conductance.
      From single-channel analysis, we concluded that channels always pass through the
      larger subconductance state on the way to and from the open state. The smaller
      subconductance state is traversed in approximately 40% of activation time
      courses. These states apparently represent kinetic intermediates in channel
      gating having voltage-dependent transitions with apparent charge movements of
      approximately 1.6 e0. The fully open T442S chimeric channel has the conductance
      sequence Rb+ > NH4+ > K+. The opposite conductance sequence, K+ > NH4+ > Rb+, is
      observed in each of the subconductance states, with the smaller subconductance
      state discriminating most strongly against Rb+.

PMID- 9236206
TI  - Increased expression of the cardiac L-type calcium channel in estrogen receptor
      deficient mice.
AB  - Steroid hormones control the expression of many cellular regulators, and a role
      for estrogen in cardiovascular function and disease has been well documented. To
      address whether the activity of the L-type Ca2+ channel, a critical element in
      cardiac excitability and contractility, is altered by estrogen and its nuclear
      receptor, we examined cardiac myocytes from male mice in which the estrogen
      receptor gene had been disrupted (ERKO mice). Binding of dihydropyridine Ca2+
      channel antagonist isradipine (PN200-110) was increased 45.6% in cardiac
      membranes from the ERKO mice compared to controls, suggesting that a lack of
      estrogen receptors in the heart increased the number of Ca2+ channels. Whole-cell
      patch clamp of acutely dissociated adult cardiac ventricular myocytes indicated
      that Ca2+ channel current was increased by 49% and action potential duration was
      increased by 75%. Examination of electrocardiogram parameters in ERKO mice showed
      a 70% increase in the QT interval without significant changes in PQ or QRS
      intervals. These results show that the membrane density of the cardiac L-type
      Ca2+ channel is regulated by the estrogen receptor and suggest that decreased
      estrogen may lead to an increase in the number of cardiac L-type Ca2+ channels,
      abnormalities in cardiac excitability, and increased risk of arrhythmia and
      cardiovascular disease.

PMID- 9236205
TI  - Functional expression of Drosophila para sodium channels. Modulation by the
      membrane protein TipE and toxin pharmacology.
AB  - The Drosophila para sodium channel alpha subunit was expressed in Xenopus oocytes
      alone and in combination with tipE, a putative Drosophila sodium channel
      accessory subunit. Coexpression of tipE with para results in elevated levels of
      sodium currents and accelerated current decay. Para/TipE sodium channels have
      biophysical and pharmacological properties similar to those of native channels.
      However, the pharmacology of these channels differs from that of vertebrate
      sodium channels: (a) toxin II from Anemonia sulcata, which slows inactivation,
      binds to Para and some mammalian sodium channels with similar affinity (Kd
      congruent with 10 nM), but this toxin causes a 100-fold greater decrease in the
      rate of inactivation of Para/TipE than of mammalian channels; (b) Para sodium
      channels are >10-fold more sensitive to block by tetrodotoxin; and (c)
      modification by the pyrethroid insecticide permethrin is >100-fold more potent
      for Para than for rat brain type IIA sodium channels. Our results suggest that
      the selective toxicity of pyrethroid insecticides is due at least in part to the
      greater affinity of pyrethroids for insect sodium channels than for mammalian
      sodium channels.

PMID- 9236207
TI  - Control of rectification and gating of cloned KATP channels by the Kir6.2
      subunit.
AB  - KATP channels are a functional complex of sulphonylurea receptor (SUR1, SUR2) and
      inward rectifier K+ (Kir6.1, Kir6.2) channel subunits. We have studied the role
      of the putative pore forming subunit (Kir6.2) in regulation of rectification and
      gating of KATP channels generated by transfection of SUR1 and Kir6.2 cDNAs in
      COSm6 cells. In the absence of internal polyvalent cations, the current-voltage
      relationship is sigmoidal. Mg2+ or spermine4+ (spm) each induces a mild inward
      rectification. Mutation of the asparagine at position 160 in Kir6.2 to aspartate
      (N160D) or glutamate (N160E) increases the degree of rectification induced by
      Mg2+ or spermine4+, whereas wild-type rectification is still observed after
      mutation to other neutral residues (alanine-N160A, glutamine-N160Q). These
      results are consistent with this residue lining the pore of the channel and
      contributing to the binding of these cations, as demonstrated for the equivalent
      site in homomeric ROMK1 (Kir1.1) channels. Since Kir6.2 contains no consensus ATP
      binding site, whereas SUR1 does, inhibition by ATP has been assumed to depend on
      interactions with SUR1. However, we found that the [ATP] causing half-maximal
      inhibition of current (Ki) was affected by mutation of N160. Channels formed from
      N160D or N160Q mutant subunits had lower apparent sensitivity to ATP (Ki,N160D =
      46.1 microM; Ki,N160Q = 62.9 microM) than wild-type, N160E, or N160A channels (Ki
      = 10.4, 17.7, 6.4 microM, respectively). This might suggest that ATP binding to
      the channel complex was altered, although examination of channel open
      probabilities indicates instead that the residue at position 160 alters the ATP
      independent open probability, i.e., it controls the free energy of the open
      state, thereby affecting the "coupling" of ATP binding to channel inhibition. The
      results can be interpreted in terms of a kinetic scheme whereby the residue at
      Kir6.2 position 160 controls the rate constants governing transitions to and from
      the open state, without directly affecting ATP binding or unbinding transitions.

PMID- 9236208
TI  - Cyclic GMP-gated channels in a sympathetic neuron cell line.
AB  - The stimulation of IP3 production by muscarinic agonists causes both
      intracellular Ca2+ release and activation of a voltage-independent cation current
      in differentiated N1E-115 cells, a neuroblastoma cell line derived from mouse
      sympathetic ganglia. Earlier work showed that the membrane current requires an
      increase in 3',5'-cyclic guanosine monophosphate (cGMP) produced through the NO
      synthase/guanylyl cyclase cascade and suggested that the cells may express cyclic
      nucleotide-gated ion channels. This was tested using patch clamp methods. The
      membrane permeable cGMP analogue, 8-br-cGMP, activates Na+ permeable channels in
      cell attached patches. Single channel currents were recorded in excised patches
      bathed in symmetrical Na+ solutions. cGMP-dependent single channel activity
      consists of prolonged bursts of rapid openings and closings that continue without
      desensitization. The rate of occurrence of bursts as well as the burst length
      increase with cGMP concentration. The unitary conductance in symmetrical 160 mM
      Na+ is 47 pS and is independent of voltage in the range -50 to +50 mV. There is
      no apparent effect of voltage on opening probability. The dose response curve
      relating cGMP concentration to channel opening probability is fit by the Hill
      equation assuming an apparent KD of 10 microm and a Hill coefficient of 2. In
      contrast, cAMP failed to activate the channel at concentrations as high as 100
      microm. Cyclic nucleotide gated (CNG) channels in N1E-115 cells share a number of
      properties with CNG channels in sensory receptors. Their presence in neuronal
      cells provides a mechanism by which activation of the NO/cGMP pathway by G
      protein-coupled neurotransmitter receptors can directly modify Ca2+ influx and
      electrical excitability. In N1E-115 cells, Ca2+ entry by this pathway is
      necessary to refill the IP3-sensitive intracellular Ca2+ pool during repeated
      stimulation and CNG channels may play a similar role in other neurons.

PMID- 9236209
TI  - Inward rectification in ClC-0 chloride channels caused by mutations in several
      protein regions.
AB  - Several cloned ClC-type Cl- channels open and close in a voltage-dependent
      manner. The Torpedo electric organ Cl- channel, ClC-0, is the best studied member
      of this gene family. ClC-0 is gated by a fast and a slow gating mechanism of
      opposite voltage direction. Fast gating is dependent on voltage and on the
      external and internal Cl- concentration, and it has been proposed that the
      permeant anion serves as the gating charge in ClC-0 (Pusch, M., U. Ludewig, A.
      Rehfeldt, and T.J. Jentsch. 1995. Nature (Lond.). 373:527-531). The deactivation
      at negative voltages of the muscular ClC-1 channel is similar but not identical
      to ClC-0. Different from the extrinsic voltage dependence suggested for ClC-0, an
      intrinsic voltage sensor had been proposed to underlie the voltage dependence in
      ClC-1 (Fahlke, C., R. Rudel, N. Mitrovic, M. Zhou, and A.L. George. 1995. Neuron.
      15:463-472; Fahlke, C., A. Rosenbohm, N. Mitrovic, A.L. George, and R. Rudel.
      1996. Biophys. J. 71:695-706). The gating model for ClC-1 was partially based on
      the properties of a point-mutation found in recessice myotonia (D136G). Here we
      investigate the functional effects of mutating the corresponding residue in ClC-0
      (D70). Both the corresponding charge neutralization (D70G) and a charge
      conserving mutation (D70E) led to an inwardly rectifying phenotype resembling
      that of ClC-1 (D136G). Several other mutations at very different positions in ClC
      0 (K165R, H472K, S475T, E482D, T484S, T484Q), however, also led to a similar
      phenotype. In one of these mutants (T484S) the typical wild-type gating,
      characterized by a deactivation at negative voltages, can be partially restored
      by using external perchlorate (ClO4-) solutions. We conclude that gating in ClC-0
      and ClC-1 is due to similar mechanisms. The negative charge at position 70 in ClC
      0 does not specifically confer the voltage sensitivity in ClC-channels, and there
      is no need to postulate an intrinsic voltage sensor in ClC-channels.

PMID- 9236210
TI  - Molecular tuning of an EF-hand-like calcium binding loop. Contributions of the
      coordinating side chain at loop position 3.
AB  - Calcium binding and signaling orchestrate a wide variety of essential cellular
      functions, many of which employ the EF-hand Ca2+ binding motif. The ion binding
      parameters of this motif are controlled, in part, by the structure of its Ca2+
      binding loop, termed the EF-loop. The EF-loops of different proteins are
      carefully specialized, or fine-tuned, to yield optimized Ca2+ binding parameters
      for their unique cellular roles. The present study uses a structurally homologous
      Ca2+ binding loop, that of the Escherichia coli galactose binding protein, as a
      model for the EF-loop in studies examining the contribution of the third loop
      position to intramolecular tuning. 10 different side chains are compared at the
      third position of the model EF-loop with respect to their effects on protein
      stability, sugar binding, and metal binding equilibria and kinetics. Substitution
      of an acidic Asp side chain for the native Asn is found to generate a 6,000-fold
      increase in the ion selectivity for trivalent over divalent cations, providing
      strong support for the electrostatic repulsion model of divalent cation charge
      selectivity. Replacement of Asn by neutral side chains differing in size and
      shape each alter the ionic size selectivity in a similar manner, supporting a
      model in which large-ion size selectivity is controlled by complex interactions
      between multiple side chains rather than by the dimensions of a single
      coordinating side chain. Finally, the pattern of perturbations generated by side
      chain substitutions helps to explain the prevalence of Asn and Asp at the third
      position of natural EF-loops and provides further evidence supporting the unique
      kinetic tuning role of the gateway side chain at the ninth EF-loop position.

PMID- 9236212
TI  - Sodium kinetics of Na,K-ATPase alpha isoforms in intact transfected HeLa cells.
AB  - By participating in the regulation of ion and voltage gradients, the Na-K pump
      (i.e., Na,K-ATPase) influences many aspects of cellular physiology. Of the four
      alpha isoforms of the pump, alpha1 is ubiquitous, alpha2 is predominant in
      skeletal muscle, and alpha3 is found in neurons and the cardiac conduction
      system. To determine whether the isoforms have different intracellular Na+
      affinities, we used the Na+-sensitive dye sodium-binding benzofuran isophthalate
      (SBFI) to measure pump-mediated Na+ efflux as a function of [Na+]i in human HeLa
      cells stably transfected with rat Na-K pump isoforms. We Na+-loaded the cells,
      and then monitored the time course of the decrease in [Na+]i after removing
      external Na+. All transfected rat alpha subunits were highly ouabain resistant:
      the alpha1 isoform is naturally resistant, whereas the alpha2 and alpha3 isoforms
      had been mutagenized to render them resistant. Thus, the Na+ efflux mediated by
      endogenous and transfected pumps could be separated by studying the cells at low
      (1 microM) and high (4 mM) ouabain concentrations. We found that the apparent Km
      for Na+ efflux attributable to the native human alpha1 isoform was 12 mM, which
      was similar to the Km of rat alpha1. The alpha2 and alpha3 isoforms had apparent
      Km's of 22 and 33 mM, respectively. The cells expressing alpha3 had a high
      resting [Na+]i. The maximal activity of native alpha1 in the alpha3-transfected
      cells was only approximately 56% of native alpha1 activity in untransfected HeLa
      cells, suggesting that transfection with alpha3 led to a compensatory decrease in
      endogenous alpha1 pumps. We conclude that the apparent Km(Na+) for rat Na-K pump
      isoforms increases in the sequence alpha1 < alpha2 < alpha3. The alpha3 isoform
      may be suited for handling large Na+ loads in electrically active cells.

PMID- 9236211
TI  - NO3--induced pH changes in mammalian cells. Evidence for an NO3--H+
      cotransporter.
AB  - The effect of NO3- on intracellular pH (pHi) was assessed microfluorimetrically
      in mammalian cells in culture. In cells of human, hamster, and murine origin
      addition of extracellular NO3- induced an intracellular acidification. This
      acidification was eliminated when the cytosolic pH was clamped using ionophores
      or by perfusing the cytosol with highly buffered solutions using patch-pipettes,
      ruling out spectroscopic artifacts. The NO3-- induced pH change was not due to
      modulation of Na+/H+ exchange, since it was also observed in Na+/H+ antiport
      deficient mutants. Though NO3- is known to inhibit vacuolar-type (V) H+-ATPases,
      this effect was not responsible for the acidification since it persisted in the
      presence of the potent V-ATPase inhibitor bafilomycin A1. NO3-/HCO3- exchange as
      the underlying mechanism was ruled out because acidification occurred despite
      nominal removal of HCO3-, despite inhibition of the anion exchanger with
      disulfonic stilbenes and in HEK 293 cells, which seemingly lack anion exchangers
      (Lee, B. S., R.B. Gunn, and R.R. Kopito. 1991. J. Biol. Chem. 266:11448- 11454).
      Accumulation of intracellular NO3-, measured by the Greiss method after reduction
      to NO2-, indicated that the anion is translocated into the cells along with the
      movement of acid equivalents. The simplest model to explain these observations is
      the cotransport of NO3- with H+ (or the equivalent counter-transport of NO3- for
      OH-). The transporter appears to be bi-directional, operating in the forward as
      well as reverse directions. A rough estimate of the fluxes of NO3- and acid
      equivalents suggests a one-to-one stoichiometry. Accordingly, the rate of
      transport was unaffected by sizable changes in transmembrane potential. The
      cytosolic acidification was a saturable function of the extracellular
      concentration of NO3- and was accentuated by acidification of the extracellular
      space. The putative NO3--H+ cotransport was inhibited markedly by ethacrynic acid
      and by alpha-cyano-4-hydroxycinnamate, but only marginally by 4, 4'
      diisothiocyanostilbene-2,2' disulfonate or by p-chloromercuribenzene sulfonate.
      The transporter responsible for NO3--induced pH changes in mammalian cells may be
      related, though not identical, to the NO3--H+ cotransporter described in
      Arabidopsis and Aspergillus. The mammalian cotransporter may be important in
      eliminating the products of NO metabolism, particularly in cells that generate
      vast amounts of this messenger. By cotransporting NO3- with H+ the cells would
      additionally eliminate acid equivalents from activated cells that are
      metabolizing actively, without added energetic investment and with minimal
      disruption of the transmembrane potential, inasmuch as the cotransporter is
      likely electroneutral.

PMID- 9236213
TI  - Dendritic computation of direction selectivity and gain control in visual
      interneurons.
AB  - The extraction of motion information from time varying retinal images is a
      fundamental task of visual systems. Accordingly, neurons that selectively respond
      to visual motion are found in almost all species investigated so far. Despite its
      general importance, the cellular mechanisms underlying direction selectivity are
      not yet understood in most systems. Blocking inhibitory input to fly visual
      interneurons by picrotoxinin (PTX), we demonstrate that their direction
      selectivity arises largely from interactions between postsynaptic signals
      elicited by excitatory and inhibitory input elements, which are themselves only
      weakly tuned to opposite directions of motion. Their joint activation by
      preferred as well as null direction motion leads to a mixed reversal potential at
      which the postsynaptic response settles for large field stimuli. Assuming the
      activation ratio of these opponent inputs to be a function of pattern velocity
      can explain how the postsynaptic membrane potential saturates with increasing
      pattern size at different levels for different pattern velocities ("gain
      control"). Accordingly, we find that after blocking the inhibitory input by PTX,
      gain control is abolished.

PMID- 9236214
TI  - Optimal nerve growth factor trophic signals mediated by synergy of TrkA and p75
      receptor-specific ligands.
AB  - Nerve growth factor (NGF) receptor-mediated signaling was studied using specific
      monoclonal antibodies (mAbs) as ligands that discriminate between the receptors
      TrkA and p75. mAb-induced trophic signals were compared with the signals of the
      natural ligand NGF. In cells expressing TrkA but no p75 receptors (TrkA+ p75(-)),
      binding of TrkA with mAb 5C3 leads to optimal signals. In cells expressing both
      TrkA and p75 (TrkA+ p75(+)), binding of TrkA with mAb 5C3 leads to significant
      but suboptimal signals, and optimal trophic signals are obtained by concomitant
      binding of TrkA and p75 with mAbs 5C3 and MC192. In TrkA+ p75(+) cells, binding
      of anti-p75 mAb MC192 also enhances the trophic effect of suboptimal
      concentrations of NGF. In contrast, in cells expressing p75 receptors singly
      (TrkA- p75(+)), binding with mAb MC192 or NGF causes very limited or no trophic
      effects. Thus, the data support the hypothesis that unbound p75 may modulate TrkA
      trophic signals. Importantly, the data also demonstrate for the first time that
      in multireceptor systems appropriate combinations of anti-receptor mAbs can fully
      mimic the signals of a polypeptide growth factor.

PMID- 9236215
TI  - Identification of a somatodendritic targeting signal in the cytoplasmic domain of
      the transferrin receptor.
AB  - Neurons are highly polarized cells that must sort proteins synthesized in the
      cell body for transport into the axon or the dendrites. Given the amount of time
      and energy needed to deliver proteins to the distal processes, neurons must have
      high fidelity mechanisms that ensure proper polarized protein trafficking.
      Although a variety of proteins are localized either to the somatodendritic domain
      or to the axon (), the question of whether there are signal-dependent mechanisms
      that sort proteins to distinct neuronal domains is only beginning to be
      addressed. To determine sequence requirements for the polarized sorting of
      transmembrane proteins into dendrites, we expressed mutant transferrin receptors
      in cultured rat hippocampal neurons, using a defective herpes virus vector. Wild
      type human transferrin receptor colocalized with the endogenous protein in
      dendritic endosomes and was strictly excluded from axons, despite overexpression.
      Polarized targeting was abolished by deletion of cytoplasmic amino acids 7-10, 11
      14, or 19-28, but not 29-42 or 43-58. These deletions also increased the
      appearance of transferrin receptor on the plasma membrane, implying that
      endocytosis and dendritic targeting are mediated by overlapping signals and
      similar molecular mechanisms. In addition, we have characterized a specialized
      para-Golgi endosome poised to play a critical role in the polarized recycling of
      transmembrane proteins.

PMID- 9236216
TI  - Galanin inhibits continuous and phasic firing in rat hypothalamic magnocellular
      neurosecretory cells.
AB  - The effects of galanin (GAL) on magnocellular neurosecretory cells (MNCs) were
      examined during microelectrode recordings from supraoptic neurons in superfused
      hypothalamic explants. Application of the full-length peptide (GAL1-29) or of the
      N-terminal fragment GAL1-16 produced reversible membrane hyperpolarization with
      an IC50 near 10 nM. These effects were associated with an increase of membrane
      conductance, with a reversal potential near -70 mV, and were not blocked by
      tetrodotoxin, indicating that the receptors mediating these effects are located
      postsynaptically. Hyperpolarizing responses were also observed in response to the
      GAL-like chimeric ligands M35 and M40, suggesting that these behave as partial
      agonists at galanin receptors. The reversal potential of the GAL-mediated effect
      was unaffected by reducing extracellular chloride or by intracellular chloride
      injection, indicating that the effects of galanin are not mediated by modulation
      of chloride conductances. In contrast, reducing the external concentration of
      potassium ions from 3 to 1 mM shifted the reversal potential of the responses to 
      85 mV, suggesting the involvement of a potassium conductance. When tested on
      spontaneously active MNCs, the hyperpolarizing effects of galanin were associated
      with a suppression of firing in both continuously active and phasically active
      neurons. Inhibition of phasic bursts was mediated both through the inhibitory
      effects of the hyperpolarization and through a GAL-mediated inhibition of the
      depolarizing afterpotential that is responsible for the production of individual
      bursts. These results suggest that galanin may be a potent endogenous modulator
      of firing pattern in hypothalamic neuroendocrine cells.

PMID- 9236217
TI  - Glutamate-dependent activation of NF-kappaB during mouse cerebellum development.
AB  - NF-kappaB and activator protein 1 (AP-1) are dimeric transcription factors
      involved in transcriptional regulation in many cells, including neurons. We have
      examined their activity during mouse cerebellum development, a postnatal process
      starting just after birth and completed by the fourth postnatal (PN) week. The
      activity of these factors was analyzed by binding of nuclear extracts to a
      synthetic oligonucleotide representing the kappaB site of human immunodeficiency
      virus or the AP-1 site of the urokinase promoter. NF-kappaB activity was observed
      from 7 PN, was restricted to the developing cerebellum, and was not observed in
      the early postnatal neocortex and hippocampus. On the other hand, AP-1 activity
      was not found in cerebellum but was present in both neocortex and hippocampus.
      Moreover, a kappaB-driven transgene was found to be increasingly expressed in the
      cerebellum from 5 PN to 10 PN but not in the adult. The regulation of NF-kappaB
      activation in mouse cerebellum was analyzed by intraperitoneal injection of
      glutamate receptor antagonists to 9 PN mice, which abolished NF-kappaB-binding
      activity, suggesting an endogenous loop of glutamate receptor activation.
      Glutamate receptor agonists, on the other hand, induced NF-kappaB nuclear
      translocation in the cerebellum of 5 PN mice, which is a stage in which NF-kappaB
      is not yet endogenously activated. This effect was specific for NF-kappaB and not
      observed for AP-1. In adult mice, NF-kappaB activity was absent in the cerebellum
      and was not induced by intraperitoneal injection of glutamate receptor agonists.
      These data show that NF-kappaB is specifically activated during cerebellum
      development and indicate an important role of glutamate receptors in this
      process.

PMID- 9236218
TI  - Serotonin and the small cardioactive peptides differentially modulate two motor
      neurons that innervate the same muscle fibers in Aplysia.
AB  - The anterior portion of intrinsic buccal muscle 3 (I3a) is innervated by two
      motor neurons, B3 and B38, which appear to use glutamate as their fast excitatory
      transmitter. B3 and B38 express the neuropeptides FMRFamide and the small
      cardioactive peptides (SCPs), respectively. We have shown previously that
      stimulation of B38 causes release of the SCPs from terminals in the muscle. The
      I3a muscle also receives input from neurons that use 5HT as a modulatory
      transmitter. The SCPs and 5HT potently facilitated B38-evoked excitatory junction
      potentials (EJPs) but had only a small effect on B3-evoked EJPs; however, both
      the SCPs and 5HT strongly potentiated contractions evoked by both B3 and B38,
      indicating that the two substances must also act on excitation-contraction
      coupling. The selective facilitation of B38-evoked EJPs, however, did manifest
      itself in other parameters. Decreases in the firing frequencies and burst
      durations that were threshold to evoke contractions and decreases in the latency
      between the onset of a burst and the onset of the evoked contraction were all
      much larger for B38 than for B3. Indeed, B38 bursts recorded during feeding-like
      behavior would be subthreshold for evoking contractions in the absence of this
      modulation. All of the effects of the SCPs reversed during washout, whereas those
      of 5HT were persistent, lasting many hours after washout. Thus, the SCPs and 5HT
      dramatically change the behavioral output of these motor neurons, increasing the
      amplitude of contractions evoked by both B3 and B38, and shifting the temporal
      relationship between bursts in B38 and its evoked contractions.

PMID- 9236219
TI  - GABAergic and glycinergic IPSCs in ganglion cells of rat retinal slices.
AB  - GABAergic and glycinergic IPSCs were studied in identified retinal ganglion cells
      (RGCs) of light-adapted rat retinal slices, using whole-cell recording
      techniques. GABAergic IPSCs were blocked specifically by SR95531 (3 microM) and
      bicuculline (3 microM) and glycinergic IPSCs by strychnine (0.3 microM). From 37
      RGCs studied, 25 showed exclusively GABAergic IPSCs, 6 presented only glycinergic
      IPSCs, and 6 showed both. This distribution may result from differences in
      amacrine cells input rather than from receptor heterogeneity, because both GABA
      and glycine elicited Cl--selective currents in all RGCs tested. TTX markedly
      reduced GABAergic IPSCs frequency, whereas glycinergic IPSCs were unaffected.
      Ca2+-free media, with or without high Mg2+, blocked TTX-resistant GABAergic and
      glycinergic IPSCs. These results suggest that GABAergic IPSCs in RGCs can be
      elicited either by Na+-dependent action potentials or by local Ca2+ influx in
      medium or large dendritic field GABAergic amacrine cells, whereas glycinergic
      IPSCs are generated by action potential-independent Ca2+ influx in narrow field
      glycinergic amacrine cells. Both types of IPSCs had fast rise times and
      biexponential decays, but glycinergic IPSC decay was significantly slower than
      that of GABAergic IPSCs. An elementary conductance of 54 pS for the glycine-gated
      channels was estimated from single-channel events, clearly detected in the
      falling phase of glycinergic IPSCs, and from responses to exogenous glycine.

PMID- 9236220
TI  - Phosphorylation at a single site in the rat brain sodium channel is necessary and
      sufficient for current reduction by protein kinase A.
AB  - Voltage-gated sodium channels respond to excitatory inputs in nerve cells,
      generating spikes of depolarization at axon hillock regions and propagating the
      initial rising phase of action potentials through axons. It previously has been
      shown that protein kinase A (PKA) attenuates sodium current amplitude 20-50% by
      phosphorylating serines located in the I-II linker of the sodium channel. We have
      tested the individual contributions of five PKA consensus sites in the I-II
      linker by measuring sodium currents expressed in Xenopus oocytes during
      conditions of PKA induction. PKA was induced by perfusing oocytes with a cocktail
      that contained forskolin, chlorophenylthio-cAMP, dibutyryl-cAMP, and 3-isobutyl-1
      methylxanthine. Phosphorylation at the second PKA site (serine-573) was necessary
      and sufficient to diminish sodium current amplitude. Phosphorylation at the third
      and fourth positions (serine-610 and serine-623) reduced current amplitude, but
      the effect was considerably smaller at those positions. Introduction of a
      negative charge at site 2 by substitution of serine-573 with an aspartate
      constitutively reduced the basal level of sodium current, indicating that the
      attenuation of sodium current by phosphorylation of site 2 by PKA results from
      the introduction of a negative charge at this site.

PMID- 9236221
TI  - Detection of functional nicotinic receptors blocked by alpha-bungarotoxin on PC12
      cells and dependence of their expression on post-translational events.
AB  - A major class of nicotinic receptors in the nervous system is one that binds
      alpha-bungarotoxin and contains the alpha7 gene product. PC12 cells, frequently
      used to study nicotinic receptors, express the alpha7 gene and have binding sites
      for the toxin, but previous attempts to elicit currents from the putative
      receptors have failed. Using whole-cell patch-clamp recording techniques and
      rapid application of agonist, we find a rapidly desensitizing acetylcholine
      induced current in the cells that can be blocked by alpha-bungarotoxin. The
      current amplitude varies dramatically among three populations of PC12 cells but
      correlates well with the number of toxin-binding receptors. In contrast, the
      current shows no correlation with alpha7 transcript; cells with high levels of
      alpha7 mRNA can be negative for toxin binding and yet have other functional
      nicotinic receptors. Northern blot analysis and reverse transcription-PCR reveal
      no defects in alpha7 RNA from the negative cells, and immunoblot analysis
      demonstrates that they contain full-length alpha7 protein, although at reduced
      levels. Affinity purification of toxin-binding receptors from cells expressing
      them confirms that the receptors contain alpha7 protein. Transfection experiments
      demonstrate that PC12 cells lacking native toxin-binding receptors are deficient
      at producing receptors from alpha7 gene constructs, although the same cells can
      produce receptors from other transfected gene constructs. The results indicate
      that nicotinic receptors that bind alpha-bungarotoxin and contain alpha7 subunits
      require additional gene products to facilitate assembly and stabilization of the
      receptors. PC12 cells offer a model system for identifying those gene products.

PMID- 9236222
TI  - The role of CED-3-related cysteine proteases in apoptosis of cerebellar granule
      cells.
AB  - The CED-3-related cysteine proteases (CRCPs) have been implicated as mediators of
      apoptosis, primarily in hematogenous cell systems, but their role in neuronal
      apoptosis remains unclear. The present study examined the role of two CRCP
      families-CPP32- and interleukin-1beta converting enzyme (ICE)-like cysteine
      proteases-in apoptosis of cerebellar granule cells (CGCs) caused by withdrawal of
      serum and/or potassium (K+). Serum deprivation potentiated apoptosis caused by K+
      withdrawal, reducing cell viability by approximately one half of control values
      after 12 hr as measured by calcein fluorescence. Cell death after serum/K+
      deprivation was significantly attenuated by the CPP32-like inhibitor z-DEVD-fmk;
      however, the ICE-like inhibitor z-YVAD-fmk had only slightly protective effects
      at the highest concentration used. Both inhibitors reduced CPP32-like activity
      directly in an in vitro fluorometric assay system, although z-DEVD-fmk showed
      much greater potency. K+ and serum/K+ deprivation each were accompanied by
      increased CPP32-like activity; however, ICE-like activity was absent after 12 hr
      of serum and/or K+ deprivation. CPP32 mRNA levels were unchanged after K+
      deprivation but increased after serum and combined serum/K+ withdrawal as
      measured by reverse transcription-PCR (RT-PCR), with peak values at 4 hr reaching
      210 +/- 37% and 269 +/- 42% of control levels, respectively. In contrast, ICE
      mRNA was undetectable by RT-PCR. These results are consistent with the hypothesis
      that CPP32-like proteases play an important role in apoptosis of CGCs caused by
      deprivation of K+ or serum/K+.

PMID- 9236223
TI  - Apolipoprotein E binds to and potentiates the biological activity of ciliary
      neurotrophic factor.
AB  - Expression of apolipoprotein E (apoE) and ciliary neurotrophic factor (CNTF), a
      pleiotropic neuron survival factor, increases in the CNS in response to injury.
      Although CNTF is believed to act as a survival factor after injury in the CNS,
      the functions of apoE in the CNS remain mainly unknown. Similarities between apoE
      and CNTF, including coinciding patterns of postinjury expression, extracellular
      localization, homologous tertiary structure, and ability to form homodimers led
      us to examine the possibility that apoE and CNTF directly associate and thereby
      facilitate the neurotrophic activity of CNTF. We identified two binding
      interactions between apoE and CNTF: (1) reversible binding of both the apoE3 and
      apoE4 isoforms to CNTF under nondenaturing conditions, and (2) a higher avidity,
      SDS-stable binding of apoE3 with CNTF. Purified lipid-free apoE, as well as apoE
      in cerebrospinal fluid, binds CNTF. We demonstrate here that the survival
      promoting activity of CNTF on cultured hippocampal neurons is potentiated by
      apoE. In the absence of apoE, survival of hippocampal neurons with 1 ng/ml CNTF
      was 20% above control survival values. In contrast, in the presence of apoE,
      survival of hippocampal neurons with 1 ng/ml CNTF was 40% above control survival
      values. These data, which indicate a novel function for apoE in the nervous
      system, support the hypothesis that apoE secreted locally at sites of injury can
      facilitate neural repair by promoting the activity of certain growth factors, in
      particular CNTF.

PMID- 9236224
TI  - Nerve growth factor induces transcription of the p21 WAF1/CIP1 and cyclin D1
      genes in PC12 cells by activating the Sp1 transcription factor.
AB  - The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by
      gradually exiting from the cell cycle and differentiating to a sympathetic
      neuronal phenotype. We have shown previously () that NGF induces the expression
      of the p21 WAF1/CIP1/Sdi1 (p21) cyclin-dependent kinase (Cdk) inhibitor protein
      and the G1 phase cyclin, cyclin D1. In this report, we show that induction is at
      the level of transcription and that the DNA elements in both promoters that are
      required for NGF-specific induction are clusters of binding sites for the Sp1
      transcription factor. NGF also induced a synthetic promoter with repeated Sp1
      sites linked to a core promoter, and a plasmid regulated by a chimeric
      transactivator in which the Gal4 DNA binding domain is fused to the Sp1
      transactivation domain, indicating that this transactivation domain is regulated
      by NGF. Epidermal growth factor, which is a weak mitogen for PC12, failed to
      induce any of these promoter constructs. We consider a model in which the PC12
      cell cycle is arrested as p21 accumulates and attains inhibitory levels relative
      to Cdk/cyclin complexes. Sustained activation of p21 expression is proposed to be
      a distinguishing feature of the activity of NGF that contributes to PC12 growth
      arrest during differentiation

PMID- 9236225
TI  - High intracellular Cl- concentrations depress G-protein-modulated ionic
      conductances.
AB  - Numerous G-protein-modulated ionic conductances are present in central neurons
      and play major roles in regulating neuronal excitability. Accordingly, endogenous
      factors that alter the operation of these conductances may have profound effects
      on neuronal function. We now report that several G-protein-modulated ionic
      conductances in hippocampal neurons are very much altered when Cl- is the
      predominant anion in the recording electrode. We used both sharp-electrode and
      whole-cell techniques in rat hippocampal slices to determine whether hippocampal
      CA1 pyramidal cell properties are altered by KCl-filled, as compared with KCH3SO3
      or K-gluconate-filled, electrodes. We studied the effects of the anions on
      synaptically evoked GABAB responses and baclofen- and serotonin-induced currents
      as well as on a voltage-activated cation current, Ih. High intracellular
      concentrations of chloride ([Cl-]i) depressed all the responses without altering
      resting cell properties. Intermediate [Cl-]i reduced baclofen-induced currents as
      well as Ih in a dose-dependent manner. In KCH3SO3-filled cells, equimolar
      substitution of GTPgammaS for Tris-GTP results in activation of a K+ conductance
      that hyperpolarizes cells and lowers their input resistance. These effects of
      GTPgammaS were blocked in KCl-filled cells. In view of the tight coupling between
      the G-protein and activation of the GABAB-activated K+ conductance, the effect of
      Cl- ions is likely to be exerted either on the G-protein or the K+ channel
      itself. We observed substantial effects of Cli- at concentrations that are
      believed to exist during development in the CNS as well as during pathological
      conditions, such as spreading depression. Thus, the results we describe must be
      taken into consideration during such physiological and pathological conditions as
      well as in experimental studies of G-protein-modulated conductances.

PMID- 9236226
TI  - Increased neuronal endocytosis and protease delivery to early endosomes in
      sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of
      increased beta-amyloidogenesis.
AB  - The early endosome is the first vacuolar compartment along the endocytic pathway.
      It is the site of internalization and initial processing of amyloid precursor
      protein (APP) and apolipoprotein E (ApoE), two proteins of etiological importance
      in Alzheimer's disease, and a putative site of beta-amyloid peptide (Abeta)
      formation. Here, we identify early endosomes in human pyramidal neurons, using
      specific compartmental markers and morphometry, and show that in Alzheimer's
      disease individual endosomes display up to 32-fold larger volumes than the normal
      average. Endosomal enlargement contributed to an average 2.5-fold larger total
      endosomal volume per neuron, implying a marked increase in endocytic activity.
      Endosomal alterations were evident in most pyramidal neurons in Alzheimer brain,
      detectable at early stages of the disease but absent in several other
      neurodegenerative disorders examined. In addition, mature and proenzyme forms of
      the proteases cathepsin B and cathepsin D, a candidate APP secretase, were
      identified in most early endosomes in Alzheimer brains but were detectable in
      only a minor proportion of endosomes in normal brain. Expression of the cation
      dependent 46 kDa mannose 6-phosphate receptor was elevated in pyramidal neurons
      of Alzheimer brains, which could be a possible basis for the altered cathepsin
      trafficking pattern. Enhanced endocytic activity, coupled with increased
      trafficking to endosomes of proteases, which may have the ability under
      pathological conditions to generate Abeta, constitutes a potential mechanism by
      which beta-amyloidogenesis may become accelerated in sporadic AD and also be
      subject to influences by ApoE.

PMID- 9236227
TI  - N-Type calcium channels in the developing rat hippocampus: subunit, complex, and
      regional expression.
AB  - The expression of multiple classes of voltage-dependent calcium channels (VDCCs)
      allows neurons to tailor calcium signaling to functionally discrete cellular
      regions. In the developing hippocampus a central issue is whether the expression
      of VDCC subtypes plays a role in key phases such as migration and synaptogenesis.
      Using radioligand binding and immunoblotting, we show that some N-type VDCCs
      exist before birth, consistent with a role in migration; however, most N-VDCC
      subunit expression is postnatal, coinciding with synaptogenesis.
      Immunoprecipitation studies indicate that the increased expression of N-VDCCs in
      early development occurs without subunit switching because there is no change in
      the fraction of beta3 subunits in the N-VDCC alpha1B-beta3 heteromers.
      Fluorescence imaging of cell surface N-VDCCs during this period reveals that N
      VDCCs are expressed on somata before dendrites and that this expression is
      asynchronous between different subfields of the hippocampus (CA3-CA4 before CA1
      CA2 and dentate gyrus). Our data argue that N-VDCC expression is an important cue
      in the genesis of synaptic transmission in discrete hippocampal subfields.

PMID- 9236229
TI  - Global ischemia induces downregulation of Glur2 mRNA and increases AMPA receptor
      mediated Ca2+ influx in hippocampal CA1 neurons of gerbil.
AB  - Transient, severe forebrain or global ischemia leads to delayed cell death of
      pyramidal neurons in the hippocampal CA1. The precise molecular mechanisms
      underlying neuronal cell death after global ischemia are as yet unknown.
      Glutamate receptor-mediated Ca2+ influx is thought to play a critical role in
      this cell death. In situ hybridization revealed that the expression of mRNA
      encoding GluR2 (the subunit that limits Ca2+ permeability of AMPA-type glutamate
      receptors) was markedly and specifically reduced in gerbil CA1 pyramidal neurons
      after global ischemia but before the onset of neurodegeneration. To determine
      whether the change in GluR2 expression is functionally significant, we examined
      the AMPA receptor-mediated rise in cytoplasmic free Ca2+ level ([Ca2+]i) in
      individual CA1 pyramidal neurons by optical imaging with the Ca2+ indicator dye
      fura-2 and by intracellular recording. Seventy-two hours after ischemia, CA1
      neurons that retained the ability to fire action potentials exhibited a greatly
      enhanced AMPA-elicited rise in [Ca2+]i. Basal [Ca2+]i in these neurons was
      unchanged. These findings provide evidence for Ca2+ entry directly through AMPA
      receptors in pyramidal neurons destined to die. Downregulation of GluR2 gene
      expression and an increase in Ca2+ influx through AMPA receptors in response to
      endogenous glutamate are likely to contribute to the delayed neuronal death after
      global ischemia.

PMID- 9236228
TI  - Establishment of a cell-free system of neuronal apoptosis: comparison of
      premitochondrial, mitochondrial, and postmitochondrial phases.
AB  - Apoptosis is a fundamental process required for normal development of the nervous
      system and is triggered during neurodegenerative disease. To dissect the
      molecular events leading to neuronal cell death, we have developed a cell-free
      model of neuronal apoptosis. The model faithfully reproduces key elements of
      apoptosis, including chromatin condensation, DNA fragmentation, caspase
      activation/processing, and selective substrate cleavage. We report that cell-free
      apoptosis is activated in premitochondrial, mitochondrial, and postmitochondrial
      phases by tamoxifen, mastoparan, and cytochrome c, respectively, allowing a
      functional ordering of these proapoptotic modulators. Furthermore, this is the
      first report of mitochondrial-mediated activation of cell-free apoptosis in a
      cell extract. Although Bcl-2 blocks activation at the premitochondrial and
      mitochondrial levels, it does not affect the postmitochondrial level. The cell
      free system described here provides a valuable tool to elucidate the molecular
      events leading to neuronal cell death.

PMID- 9236230
TI  - Calcium controls gene expression via three distinct pathways that can function
      independently of the Ras/mitogen-activated protein kinases (ERKs) signaling
      cascade.
AB  - Calcium ions are the principal second messenger in the control of gene expression
      by electrical activation of neurons. However, the full complexity of calcium
      signaling pathways leading to transcriptional activation and the cellular
      machinery involved are not known. Using the c-fos gene as a model system, we show
      here that the activity of its complex promoter is controlled by three
      independently operating signaling mechanisms and that their functional
      significance is cell type-dependent. The serum response element (SRE), which is
      composed of a ternary complex factor (TCF) and a serum response factor (SRF)
      binding site, integrates two calcium-signaling pathways. In PC12 cells, calcium
      regulated transcription mediated by the SRE requires the TCF site and is not
      inhibited by expression of the dominant-negative Ras mutant, RasN17, nor by the
      MAP kinase kinase 1 inhibitor PD 98059. In contrast, TCF-dependent
      transcriptional regulation by nerve growth factor or epidermal growth factor is
      mediated by a Ras/MAP kinases (ERKs) pathway targeting the TCF Elk-1. In AtT20
      cells and hippocampal neurons, calcium signals can stimulate transcription via a
      TCF-independent mechanism that requires the SRF binding site. The cyclic AMP
      response element (CRE), which cooperates with the TCF site in growth factor
      regulated transcription, is a target of a third calcium-regulated pathway that is
      little affected by the expression of RasN17 or by PD 98059. Thus, calcium can
      stimulate gene expression via a TCF-, SRF-, and CRE-linked pathway that can
      operate independently of the Ras/MAP kinases (ERKs) signaling cascade in a cell
      type-dependent manner.

PMID- 9236231
TI  - Growth factor activity of endothelin-1 in primary astrocytes mediated by adhesion
      dependent and -independent pathways.
AB  - Endothelin-1 (ET-1) has been shown to induce DNA synthesis in primary astrocytes
      by stimulating the extracellular signal-regulated kinase (ERK) pathway. To
      clarify the mechanisms responsible for the anchorage-dependent growth of
      astrocytes, the relationships between cell adhesion and ERK activation were
      investigated. Here it is reported that ET-1 promotes the formation of stress
      fibers and focal adhesions and the tyrosine phosphorylation of focal adhesion
      kinase (FAK) and paxillin, as well as Src activation and association of
      phosphorylated FAK with Grb2. Pretreatment of astrocytes with cytochalasin D or
      C3-transferase, which inhibits actin polymerization or Rho activity,
      respectively, prevented the activation/phosphorylation of Src, FAK, and paxillin
      after ET-1 stimulation; by contrast, the ERK pathway was not significantly
      affected. This differential activation of FAK/Src and ERK pathways was also
      observed with astrocytes 10 and 60 min after replating on poly-L-ornithine
      precoated dishes. Collectively, these findings indicate that activation of FAK
      and Src is dependent on actin cytoskeleton integrity, Rho activation, and
      adhesion to extracellular matrix, whereas ERK activation is independent of these
      intracellular events and seems to correlate with activation of the newly
      identified protein tyrosine kinase PYK2. Induction of DNA synthesis by ET-1,
      however, was reduced dramatically in astrocytes pretreated with either
      cytochalasin D or C3-transferase. This study provides a demonstration of Rho- and
      adhesion-dependent activation of FAK/Src, which collaborates with adhesion
      independent activation of PYK2/ERK for DNA synthesis in ET-1-stimulated
      astrocytes.

PMID- 9236233
TI  - Differential localization of voltage-dependent calcium channel alpha1 subunits at
      the human and rat neuromuscular junction.
AB  - Neurotransmitter release is regulated by voltage-dependent calcium channels
      (VDCCs) at synapses throughout the nervous system. At the neuromuscular junction
      (NMJ) electrophysiological and pharmacological studies have identified a major
      role for P- and/or Q-type VDCCs in controlling acetylcholine release from the
      nerve terminal. Additional studies have suggested that N-type channels may be
      involved in neuromuscular transmission. VDCCs consist of pore-forming alpha1 and
      regulatory beta subunits. In this report, using fluorescence immunocytochemistry,
      we provide evidence that immunoreactivity to alpha1A, alpha1B, and alpha1E
      subunits is present at both rat and human adult NMJs. Using control and
      denervated rat preparations, we have been able to establish that the subunit
      thought to correspond to P/Q-type channels, alpha1A, is localized presynaptically
      in discrete puncta that may represent motor nerve terminals. We also demonstrate
      for the first time that alpha1A and alpha1B (which corresponds to N-type
      channels) may be localized in axon-associated Schwann cells and, further, that
      the alpha1B subunit may be present in perisynaptic Schwann cells. In addition,
      the alpha1E subunit (which may correspond to R/T-type channels) seems to be
      localized postsynaptically in the muscle fiber membrane and concentrated at the
      NMJ. The possibility that all three VDCCs at the NMJ are potential targets for
      circulating autoantibodies in amyotrophic lateral sclerosis is discussed.

PMID- 9236232
TI  - Lack of neurotrophin 3 causes losses of both classes of spiral ganglion neurons
      in the cochlea in a region-specific fashion.
AB  - Essential functions of neurotrophin 3 (NT-3) in regulating afferent and efferent
      innervation of the cochlea have been characterized by comparison of normal and NT
      3 mutant mice. NT-3 deficiency has striking, region-specific effects, with
      complete loss of sensory neurons in the basal turn and dramatic but incomplete
      neuronal loss in the middle and apical turns. The sensory innervation of inner
      and outer hair cells was reorganized in mutant animals. Instead of a strictly
      radial pattern of innervation, the axons of remaining sensory neurons projected
      spirally along the row of inner hair cells to innervate even the most basal inner
      hair cells. Innervation of outer hair cells was strongly reduced overall and was
      not detected in the basal turn. The presence of fibers extending to both inner
      and outer hair cells suggests that subsets of types I and II sensory neurons
      survive in the absence of NT-3. Likewise, projections of the cochlea to auditory
      nuclei of the brainstem were attenuated but otherwise present. Equally striking
      changes in efferent innervation were observed in mutant animals that closely
      mimicked the abnormal sensory innervation pattern. Despite these impressive
      innervation deficiencies, the morphology of the organ of Corti and the
      development of inner and outer hair cells appeared comparatively normal.

PMID- 9236234
TI  - A genetic animal model of human neocortical heterotopia associated with seizures.
AB  - Malformations of the human neocortex are commonly associated with developmental
      delays, mental retardation, and epilepsy. This study describes a novel
      neurologically mutant rat exhibiting a forebrain anomaly resembling the human
      neuronal migration disorder of double cortex. This mutant displays a
      telencephalic internal structural heterotopia (tish) that is inherited in an
      autosomal recessive manner. The bilateral heterotopia is prominent below the
      frontal and parietal neocortices but is rarely observed in temporal neocortex.
      Neurons in the heterotopia exhibit neocortical-like morphologies and send typical
      projections to subcortical sites; however, characteristic lamination and radial
      orientation are disturbed in the heterotopia. The period of neurogenesis during
      which cells in the heterotopia are generated is the same as in the normotopic
      neocortex; however, the cells in the heterotopia exhibit a "rim-to-core"
      neurogenetic pattern rather than the characteristic "inside-out" pattern observed
      in normotopic neocortex. Similar to the human syndrome of double cortex, some of
      the animals with the tish phenotype exhibit spontaneous recurrent electrographic
      and behavioral seizures. The tish rat is a unique neurological mutant that shares
      several features with a human cortical malformation associated with epilepsy. On
      the basis of its regional connectivity, histological composition, and period of
      neurogenesis, the heterotopic region in the tish rat is neocortical in nature.
      This neurological mutant represents a novel model system for investigating
      mechanisms of aberrant neocortical development and is likely to provide insights
      into the cellular and molecular events contributing to seizure development in
      dysplastic neocortex.

PMID- 9236235
TI  - Nerve terminal withdrawal from rat neuromuscular junctions induced by neuregulin
      and Schwann cells.
AB  - Schwann cells (SCs) that cap neuromuscular junctions (nmjs) play roles in guiding
      nerve terminal growth in paralyzed and partially denervated muscles; however, the
      role of these cells in the day-to-day maintenance of this synapse is obscure.
      Neuregulins, alternatively spliced ligands for several erbB receptor tyrosine
      kinases, are thought to play important roles in cell-cell communication at the
      nmj, affecting synapse-specific gene expression in muscle fibers and the survival
      of terminal SCs during development. Here we show that application of a soluble
      neuregulin isoform, glial growth factor II (GGF2), to developing rat muscles
      alters terminal SCs, nerve terminals, and muscle fibers. SCs extend processes and
      migrate from the synapse. Nerve terminals retract from acetylcholine receptor
      rich synaptic sites, and their axons grow, in association with SCs, to the ends
      of the muscle. These axons make effective synapses only after withdrawal of GGF2.
      These synaptic alterations appear to be induced by the actions of neuregulin on
      SCs, because SC transplants growing into contact with synaptic sites also caused
      withdrawal of nerve terminal branches. These results show that SCs can alter
      synaptic structure at the nmj and implicate these cells in the maintenance of
      this synapse.

PMID- 9236237
TI  - Temporal correlations between functional and molecular changes in NMDA receptors
      and GABA neurotransmission in the superior colliculus.
AB  - Activation of the NMDA subtype of glutamate receptor is required for activity
      dependent structural plasticity in many areas of the young brain. Previous work
      has shown that NMDA receptor currents decline approximately at the time that
      developmental synaptic plasticity ends, and in situ hybridization studies have
      suggested that receptor subunit changes may be occurring during the same
      developmental interval. To establish a system in which the relationship between
      these properties of developing synapses can be explored, we have combined patch
      clamp recordings with mRNA- and protein-level biochemical analyses to study the
      developmental regulation of NMDA receptors in the superficial layers of the rat
      superior colliculus. These experiments document an abrupt decrease in the NMDA
      receptor contribution to synaptic currents that occurs before eye opening and is
      closely associated with changes in NR1 protein, rapidly rising levels of the NMDA
      receptor subunit NR2A, and decreasing levels of NR2B. The functional and
      molecular changes also are correlated with the developmental decline in
      structural plasticity in these layers. In addition, both physiological and
      biochemical methods show evidence of GABA-mediated inhibition in the superficial
      collicular layers beginning after eye opening. This may provide an additional
      heterosynaptic mechanism for controlling excitation and plasticity in this
      neuropil by pattern vision. Thus our findings lend support to the idea that high
      levels of NMDA receptor function are associated with the potential for structural
      rearrangement in CNS neuropil and that the functional downregulation of this
      molecule results, at least partially, from changes in its subunit composition.

PMID- 9236236
TI  - Rac1 mediates collapsin-1-induced growth cone collapse.
AB  - Collapsin-1 or semaphorin III(D) inhibits axonal outgrowth by collapsing the
      lamellipodial and filopodial structures of the neuronal growth cones. Because
      growth cone collapse is associated with actin depolymerization, we considered
      whether small GTP-binding proteins of the rho subfamily might participate in
      collapsin-1 signal transduction. Recombinant rho, rac1, and cdc42 proteins were
      triturated into embryonic chick (DRG) neurons. Constitutively active rac1
      increases the proportion of collapsed growth cones, and dominant negative rac1
      inhibits collapsin-1-induced collapse of growth cones and collapsin-1 inhibition
      of neurite outgrowth. DRG neurons treated with dominant negative rac1 remain
      sensitive to myelin-induced growth cone collapse. Similar mutants of cdc42 do not
      alter growth cone structure, neurite elongation, or collapsin-1 sensitivity.
      Whereas the addition of activated rho has no effect, the inhibition of rho with
      Clostridium botulinum C3 transferase stimulates the outgrowth of DRG neurites. C3
      transferase-treated growth cones exhibit little or no lamellipodial spreading and
      are minimally responsive to collapsin-1 and myelin. These data demonstrate a
      prominent role for rho and rac1 in modulating growth cone motility and indicate
      that rac1 may mediate collapsin-1 action.

PMID- 9236238
TI  - Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal
      cells in vitro.
AB  - The hedgehog gene family encodes secreted proteins important in many
      developmental patterning events in both vertebrates and invertebrates. In the
      Drosophila eye disk, hedgehog controls the progression of photoreceptor
      differentiation in the morphogenetic furrow. To investigate whether hedgehog
      proteins are also involved in the development of the vertebrate retina at stages
      of photoreceptor differentiation, we analyzed expression of the three known
      vertebrate hedgehog genes. We found that Sonic hedgehog and Desert hedgehog are
      expressed in the developing retina, albeit at very low levels, whereas Indian
      hedgehog (Ihh) is expressed in the developing and mature retinal pigmented
      epithelium, beginning at embryonic day 13. To determine whether hedgehog proteins
      have activities on developing retinal cells, we used an in vitro system in which
      much of retinal histogenesis is recapitulated. N-terminal recombinant Sonic
      Hedgehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, and the
      numbers of retinal cells of various phenotypes were analyzed by
      immunohistochemistry. We found that SHH-N caused a transient increase in the
      number of retinal progenitor cells, and a 2- to 10-fold increase in the number of
      photoreceptors differentiating in the cultures when analyzed with three different
      photoreceptor-specific antigens. In contrast, the numbers of retinal ganglion
      cells and amacrine cells were similar to those in control cultures. These results
      show that Hedgehog proteins can regulate mitogenesis and photoreceptor
      differentiation in the vertebrate retina, and Ihh is a candidate factor from the
      pigmented epithelium to promote retinal progenitor proliferation and
      photoreceptor differentiation.

PMID- 9236239
TI  - Pattern formation in the basilar papilla: evidence for cell rearrangement.
AB  - The avian basilar papilla is composed of hair and supporting cells arranged in a
      regular pattern in which the hair cells are surrounded and isolated from each
      other by supporting cell processes. This arrangement of cells, in which the
      apical borders of hair cells do not contact one another, may be generated by
      contact-mediated lateral inhibition. Little is known, however, about the way in
      which hair and supporting cells are organized during development. Whole mounts
      double-labeled with antibodies to the 275 kDa hair-cell antigen and the tight
      junction protein cingulin were therefore used to examine the development of cell
      patterns in the basilar papilla. Hair cells that contact each other at their
      apical borders are seen during early development, especially on embryonic days
      (E) 8 and 9, but are no longer observed after E12. Hair and supporting cell
      patterns were analyzed in three different areas of the papilla at E9 and E12. In
      two of these regions between E9 and E12, the ratio of supporting cells to hair
      cells does not change significantly, whereas there is an increase in both the
      number of supporting cells around each hair cell and the number of hair cells
      that each supporting cell contacts. In the third region examined, there is a
      dramatic rise in the number of supporting cells around each hair cell, which
      although accompanied by a small, significant increase in the ratio of supporting
      cells to hair cells cannot be accounted for by an increase in supporting cell
      numbers. These data show that a rearrangement of hair and supporting cells with
      respect to one another may be a fundamental process underlying the development of
      a regular pattern in the basilar papilla.

PMID- 9236240
TI  - Developmental changes in calcium current pharmacology and somatostatin inhibition
      in chick parasympathetic neurons.
AB  - Voltage-dependent calcium (Ca2+) currents were characterized and modulatory
      effects of somatostatin were measured in acutely dissociated chick ciliary
      ganglion neurons at embryonic stages 34, 37, and 40. This developmental time
      period coincides with the period of synapse formation between ciliary ganglion
      neurons and peripheral eye muscles. At all three developmental stages Ca2+
      current could be blocked almost completely by combined application of omega-CgTX
      GVIA and nitrendipine. At young embryonic ages there was significant overlap in
      sensitivity, with approximately 75% of the current sensitive to either blocker
      applied independently. By stage 40, there was very little or no overlap in
      sensitivity, with approximately 75% of the current blocked by omega-CgTX GVIA (N
      type) and 30% blocked by nitrendipine (L-type). These data are consistent with
      earlier findings that the pharmacology of acetylcholine release from ciliary
      ganglion nerve terminals changes during development from sensitivity to both
      dihydropyridines and omega-CgTX GVIA to selective sensitivity to omega-CgTX GVIA
      (Gray et al., 1992). Somatostatin reduced Ca2+ current by 50-60% at all three
      developmental stages. At early developmental stages somatostatin receptors
      coupled predominantly to the current that was sensitive to both omega-CgTX GVIA
      and nitrendipine. By stage 40, somatostatin primarily inhibited classically
      defined N-type current (selectively sensitive to omega-CgTX GVIA). Thus,
      somatostatin receptor coupling to Ca2+ channels persisted throughout development
      as Ca2+ current pharmacology changed.

PMID- 9236241
TI  - Afferent innervation influences the development of dendritic branches and spines
      via both activity-dependent and non-activity-dependent mechanisms.
AB  - The present investigation uses an in vitro co-culture system to study the role of
      afferent innervation in early development and differentiation of hippocampal
      neurons. Our experiments indicate that the formation of two key morphological
      features, dendritic branches and dendritic spines, is induced by afferent
      innervation. Hippocampal neurons develop multiple dendritic branches and spines
      only when extensively innervated by living axonal afferents. No morphological
      changes occurred when hippocampal neurons were plated on other cell surfaces such
      as fixed axons or astrocytes. Furthermore, afferents exerted their effect locally
      on individual dendrites that they contacted. When one portion of the dendritic
      arbor of a neuron was contacted by afferents and the other portion was not,
      morphological effects were restricted to the innervated dendrites. Innervation of
      some of the dendrites on a neuron did not produce global effects throughout the
      neuron. Afferent-induced dendritic branching is independent of activity, since
      branch induction was unaffected by chronic application of TTX or glutamate
      receptor blockers. In contrast, the formation of dendritic spines is influenced
      by activity. The number of developing spines was reduced when TTX or a cocktail
      of three glutamate receptor blockers was applied. Blockade of individual AMPA,
      NMDA, or metabotropic glutamate receptors did not affect the number of spines.
      These results, taken together, demonstrate that afferents can have a prominent
      influence on the development of postsynaptic target cells via both activity
      dependent and non-activity-dependent mechanisms, indicating the presence of
      multiple signals. Accordingly, this suggests an important interplay between pre-
      and postsynaptic elements early in development.

PMID- 9236243
TI  - Hand/face border as a limiting boundary in the body representation in monkey
      somatosensory cortex.
AB  - Horizontal intracortical connections may form one substrate for representational
      plasticity in somatosensory cortex. Electrophysiological mapping demonstrated the
      finer details of the representations of the hand, lower jaw, neck, and face in
      area 3b of normal macaque monkeys. Injections of two fluorescent tracers then
      defined the extent to which horizontal connections crossed from the face into the
      hand representations and vice versa in area 3b. Connections are widely
      distributed within cortical representations of skin areas innervated by cervical
      nerves or by the trigeminal nerve but do not cross a border defined by the
      anterior limit of the representation of skin innervated by the second cervical
      nerve. This border separates the representation of the muzzle, innervated only by
      the mandibular nerve, and the representation of the lower jaw and neck region,
      innervated by the second and third cervical nerves but overlapped by the
      mandibular nerve. Thus, the muzzle representation lacks connections with the hand
      and with the lower jaw and neck representations, but the representations of the
      hand and of the lower jaw and neck are strongly interconnected. Overlap of the
      hand and of the lower jaw and neck representations and of their horizontal
      intracortical connections may form one basis for expansions of the lower jaw
      representation into that of the hand when peripheral input from the hand is lost.
      Lack of connections with the rest of the face representation may limit this
      spread.

PMID- 9236242
TI  - P2 receptor excitation of rodent hypoglossal motoneuron activity in vitro and in
      vivo: a molecular physiological analysis.
AB  - The role of P2 receptors in controlling hypoglossal motoneuron (XII MN) output
      was examined (1) electrophysiologically, via application of ATP to the
      hypoglossal nucleus of rhythmically active mouse medullary slices and
      anesthetized adult rats; (2) immunohistochemically, using an antiserum against
      the P2X2 receptor subunit; and (3) using PCR to identify expression of P2X2
      receptor subunits in micropunches of tissue taken from the XII motor nucleus.
      Application of ATP to the hypoglossal nucleus of mouse medullary slices and
      anesthetized rats produced a suramin-sensitive excitation of hypoglossal nerve
      activity. Additional in vitro effects included potentiation of inspiratory
      hypoglossal nerve output via a suramin- and pyridoxal-phosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS)-sensitive mechanism, XII MN depolarization via
      activation of a suramin-sensitive inward current, decreased neuronal input
      resistance, and a slow-onset theophylline-sensitive reduction of inspiratory
      output likely resulting from hydrolysis of extracellular ATP to adenosine and
      activation of P1 receptors. Immunohistochemically, P2X2 receptors were detected
      in inspiratory XII MNs that were labeled with Lucifer yellow. These data,
      combined with identification of mRNA for three P2X2 receptor subunit isoforms
      within the hypoglossal nucleus (two of which have not been localized previously
      in brain) and the previous demonstration that P2X receptors are ubiquitously
      expressed in cranial and spinal motoneuron pools, support not only a role of P2
      receptors in modulating inspiratory hypoglossal activity but a general role of P2
      receptors in modulating motor outflow from the CNS.

PMID- 9236244
TI  - Massive autaptic self-innervation of GABAergic neurons in cat visual cortex.
AB  - Autapses are transmitter release sites made by the axon of a neuron on its own
      dendrites. We determined the numbers and precise subcellular position of autapses
      on different spiny and smooth dendritic cell types using intracellular biocytin
      filling in slices of adult neocortex. Potential self-innervation was light
      microscopically assessed on 10 pyramidal cells, 7 spiny stellate cells, and 41
      smooth dendritic neurons from cortical layers II-V. Putative autapses occurred on
      each smooth dendritic neuron and on seven pyramids, but not on spiny stellate
      cells. However, electron microscopic examination of all light microscopically
      predicted sites on pyramids (n = 28) showed only one case of self-innervation
      with two autapses on dendritic spines. Interneurons were classified by
      postsynaptic target distribution () and all putative autapses of seven basket,
      three dendrite-targeting, and three double bouquet cells were scrutinized. All
      basket and dendrite-targeting cells established self-innervation, the number of
      autapses being 12 +/- 7 and 22 +/- 12 (mean +/- SD), respectively; only one of
      the double bouquet cells formed autapses (n = 3). Basket cell autapses (n = 74)
      were closer to the soma (12.2 +/- 22.3 microm) than autapses established by
      dendrite-targeting cells (51.8 +/- 49.9 microm; n = 66). The degree of self
      innervation is cell type-specific. Unlike on spiny cells, autapses are abundant
      on GABAergic basket and dendrite-targeting interneurons, with subcellular
      location similar to that of synapses formed by the parent cell on other neurons.
      The extensive self-innervation may modulate integrative properties and/or the
      firing rhythm of the neuron in a manner temporally correlated with its own
      activity.

PMID- 9236245
TI  - Intracortical axonal projections of lamina VI cells of the primary somatosensory
      cortex in the rat: a single-cell labeling study.
AB  - A sample of 84 neurons in lamina VIa of rat somatosensory cortex (S1) was
      juxtacellularly labeled with biocytin, and the axons of the neurons were traced.
      Three classes of cells were identified as corticothalamic, corticocortical, and
      local circuit neurons. Corticothalamic cells (46%) are small, short pyramids
      projecting either to the ventral posteromedial nucleus alone or to the posterior
      group as well. The former are in upper lamina VI, have apical dendrites
      terminating in layer IV, and have intracortical collaterals ascending to layer IV
      as a narrow column about the size of a barrel. The latter are in the lower half
      of lamina VI, have apical dendrites terminating in layer V, and have a more
      extensive network of collaterals terminating in the upper part of lamina V.
      Corticothalamic cells do not project to distant cortical targets through
      branching axons. Corticocortical cells (44%) are small, short pyramids, inverted
      or modified pyramids, or bipolar spiny neurons. They send collaterals principally
      to infragranular layers of S1 and branches to the second somatosensory cortex,
      the motor cortex, or the corpus callosum. Local circuit neurons (10%) are basket
      cells, concentrated in upper lamina VI, having smooth, beaded dendrites and a
      rich collateral network densely covered with varicosities in layers V and VI. We
      conclude that (1) dendritic morphology and axonal arborizations of
      corticothalamic cells relate to the projection target; (2) many apparently
      diverse layer VI cells project to other cortical fields; and (3) lamina VI is a
      network for corticothalamic and corticocortical communication.

PMID- 9236246
TI  - Bengalese finches Lonchura Striata domestica depend upon auditory feedback for
      the maintenance of adult song.
AB  - Male birds of age-limited song-learning species develop their full song
      repertoires in the first year of life. For this type of song learner, once song
      is stabilized in adulthood, it is highly stereotyped and stable over time.
      Traditionally, it has been believed that age-limited song learners do not depend
      on auditory feedback for the maintenance of adult song. A recent report, however,
      showed that adult song in zebra finches, age-limited learners, does change after
      long-term deafness. We report here that another species of age-limited learner,
      Bengalese finches, depends critically on auditory feedback for adult song
      maintenance. We surgically deafened adult males and recorded song for 12 weeks
      after surgery. Results show that song degraded significantly within 1 week of
      surgery and continued to degrade over the next 11 weeks. This represents a more
      rapid degradation of song than has been seen previously in age-limited species.
      Song deficits after deafening included a marked decrease in syllable sequence
      stereotypy, skewed syllable distribution within song bouts, degradation of
      syllable phonology, and dropped, combined, and new or unrecognizable syllables.
      Decreased sequence stereotypy and combined syllables appeared within 1 week of
      deafening and did not worsen over time. Skewed syllable distributions and
      syllable phonology changes appeared after 1 week and did worsen. Occurrences of
      dropped and new syllables appeared within 1 week and increased over time.
      Comparison with other species indicates that much variability exists among
      species in the extent to which auditory feedback is necessary for song
      maintenance.

PMID- 9236247
TI  - Discrimination in the sense of flutter: new psychophysical measurements in
      monkeys.
AB  - Humans and monkeys have similar capacities to discriminate the frequencies of
      mechanical sinusoids delivered to their hands in the range that corresponds to
      the sense of flutter (10-50 Hz). Previous studies showed that monkeys can
      discriminate whether comparison stimuli are higher or lower in frequency than a
      base stimulus that does not vary from trial to trial during an experiment. We
      verified this result in two monkeys trained in this manner. To confirm that these
      animals were able to discriminate, we tested them in a variant of the task in
      which the frequency of the base stimulus changed randomly from trial to trial.
      The monkeys failed to discriminate in this new testing mode; instead they seemed
      to categorize the comparison stimuli, ignoring the base stimulus. After further
      training in the randomized base condition, the two monkeys learned to
      discriminate accurately. We then explored how the stimulation parameters affected
      performance. We found that animals could discriminate accurately with stimulus
      durations as short as 250 msec, with interstimulus intervals as long as 10 sec,
      with 50% differences between base and comparison stimulus amplitudes or when
      stimulated on a different finger. Performance did not degrade in these
      conditions, even though the monkeys had never been trained or tested under them.
      The results show that monkeys may try to categorize rather than discriminate when
      the task allows either strategy, although they are capable of performing true
      discriminations very robustly. These findings have important implications for
      investigating the neuronal processes underlying sensory discrimination.

PMID- 9236249
TI  - Physiology and plasticity of morphologically identified cells in the mormyrid
      electrosensory lobe.
AB  - The electrosensory lobe (ELL) of mormyrid electric fish is the first stage in the
      central processing of sensory input from electroreceptors. The responses of cells
      in ELL to electrosensory input are strongly affected by corollary discharge
      signals associated with the motor command that drives the electric organ
      discharge (EOD). This study used intracellular recording and staining to describe
      the physiology of three major cell types in the mormyrid ELL: the medium ganglion
      cell, the large ganglion cell, and the large fusiform cell. The medium ganglion
      cell is a Purkinje-like interneuron, whereas the large ganglion and large
      fusiform cells are efferent neurons that convey electrosensory information to
      higher stages of the system. Clear differences were observed among the three cell
      types. Medium ganglion cells showed two types of spikes, a small narrow spike and
      a large broad spike that were probably of axonal and dendro-somatic origin,
      respectively, whereas the large ganglion and large fusiform cells showed only
      large narrow spikes. Most of the medium ganglion cells and all of the large
      ganglion cells were inhibited by electrosensory stimuli in the center of their
      receptive fields, whereas the large fusiform cells were excited by such stimuli.
      Responses to the EOD corollary discharge were different in the three cell types,
      and these responses underwent plastic changes after a few minutes of pairing with
      an electrosensory stimulus. Plastic changes were also observed in medium and
      large ganglion cells after the corollary discharge was paired with depolarizing,
      intracellular current pulses.

PMID- 9236248
TI  - Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness
      and cataplexy in canine narcolepsy.
AB  - The therapeutic potential of thyrotropin-releasing hormone (TRH) and TRH analogs
      in narcolepsy, a sleep disorder characterized by abnormal rapid eye movement
      (REM) sleep and daytime sleepiness, was examined using the canine model. The
      effects of TRH and the biologically stable TRH analogs CG3703, CG3509, and TA0910
      on daytime sleep and cataplexy, a symptom of abnormal REM sleep, were assessed
      using polysomnographic recordings and the food elicited cataplexy test (FECT),
      respectively. CG3703 (100 and 400 microg/kg, i.v.) and TA0910 (100 and 400
      microg/kg, i.v.) significantly increased wakefulness and decreased sleep in
      narcoleptic canines, whereas TRH (400 and 1600 microg/kg, i.v.) had no
      significant effect. TRH (25-1600 microg/kg, i.v.) and all three TRH analogs,
      CG3703 (6. 25-400 microg/kg, i.v., and 0.25-16 mg/kg, p.o.), CG3509 (25-1600
      microg/kg, i.v.), and TA0910 (25-1600 microg/kg, i.v.), significantly reduced
      cataplexy in canine narcolepsy. These compounds did not produce any significant
      side effects during behavioral assays, nor did they alter free T3 and T4 levels
      in serum even when used at doses that completely suppressed cataplexy. Although
      more work is needed to establish the mode of action of TRH analogs on alertness
      and REM sleep-related symptoms, our results suggest a possible therapeutic
      application for TRH analogs in human sleep disorders.

PMID- 9236250
TI  - Role of the septum in the excitatory effect of corticotropin-releasing hormone on
      the acoustic startle reflex.
AB  - Intracerebroventricular administration of corticotropin-releasing hormone (CRH)
      elicits a constellation of behavioral, autonomic, and endocrinological changes
      typically observed in stress. One of the behavioral changes after
      intracerebroventricular CRH is a profound increase of startle amplitude (CRH
      enhanced startle). The present study examined the role of the septum in CRH
      enhanced startle. The septum has direct and indirect connections to the amygdala
      and inhibits the amygdala. Electrophysiological data show that CRH in the septum
      is inhibitory. Therefore, it has been hypothesized that intracerebroventricular
      CRH inhibits the septum, which in turn disinhibits the amygdala, resulting in a
      constellation of changes via activation of amygdala efferent targets. In testing
      this hypothesis, it was found that electrolytic lesions of the medial septum, but
      not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing
      chemical lesions of the medial septum did not block CRH-enhanced startle,
      suggesting that the blockade seen with the electrolytic lesions was caused by
      damage to fibers of passage. A major fiber bundle passing through the medial
      septum is the fornix, the primary efferent pathway for the hippocampus. Fimbria
      transection blocked CRH-enhanced startle almost completely, whereas the large
      electrolytic lesions of the dorsal hippocampus did not block CRH-enhanced
      startle. Taken together, these data suggest that perhaps the ventral hippocampus
      and its efferent target areas, which communicate via the fimbria, may be
      critically involved in CRH-enhanced startle.

PMID- 9236251
TI  - Role of the hippocampus, the bed nucleus of the stria terminalis, and the
      amygdala in the excitatory effect of corticotropin-releasing hormone on the
      acoustic startle reflex.
AB  - Previously, we demonstrated that transection of the fimbria/fornix blocked the
      excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH
      enhanced startle), suggesting that the hippocampus and its efferent target areas
      that communicate via the fimbria may be critically involved in CRH-enhanced
      startle. The bed nucleus of the stria terminalis (BNST) receives direct
      projections from the ventral hippocampus via the fimbria/fornix. Therefore, the
      role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced
      startle was investigated. NMDA lesions of the BNST completely blocked CRH
      enhanced startle, whereas chemical lesions of the ventral hippocampus and the
      amygdala failed to block CRH-enhanced startle. However, the same amygdala
      lesioned animals showed a complete blockade of fear-potentiated startle, a
      conditioned fear response sensitive to manipulations of the amygdala. In
      contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates
      a double dissociation between the BNST and the amygdala in two different
      paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST,
      but not into the ventral hippocampus, mimicked intracerebroventricular CRH
      effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH
      enhanced startle in a dose-dependent manner. Control studies showed that this
      blockade did not result from either leakage of the antagonist into the
      ventricular system or a local anesthetic effect caused by infusion of the
      antagonist into the BNST. The present studies strongly suggest that CRH in the
      CSF can activate the BNST, which could lead to activation of brainstem and
      hypothalamic BNST target areas involved in anxiety and stress responses.

PMID- 9236252
TI  - Anterior forebrain neurons develop selectivity by an intermediate stage of
      birdsong learning.
AB  - Auditory neurons of the anterior forebrain (AF) in adult zebra finches are highly
      selective for the bird's own song (BOS): they respond more to BOS than to songs
      of other zebra finches (conspecifics) and to BOS played in reverse. In contrast,
      juvenile AF neurons are not selective at 30 d of age, responding equally well to
      all song stimuli. Both BOS and tutor song experience are required by juveniles
      for normal song learning and may produce the selective properties of adult
      neurons. Because such selectivity could subserve song learning, it is important
      to determine when it arises. Birds were therefore studied at an intermediate
      stage of learning, after substantial experience of both tutor song and their own
      developing (plastic) song. Extracellular single neuron recordings in 60-d-old
      zebra finches revealed that AF neurons had significant song and order selectivity
      for both tutor song and BOS (the bird's plastic song). The degree of BOS
      selectivity was less than that found in adults, as indicated in part by 60 d
      neurons that were sensitive to the local order within syllables but not yet to
      the global order of syllables within a song. When responses to BOS and tutor song
      were compared, most neurons preferred BOS, some preferred tutor song, and others
      responded equally to both stimuli. The latter type of neuron was not simply
      immature, because many of these neurons responded significantly more to BOS and
      tutor song than to conspecific and reverse songs. The selectivity of AF neurons
      at 60 d is markedly different from the unselective properties of neurons at 30 d
      and may function in vocal learning at this stage. Moreover, the selectivity for
      both BOS and tutor song raises the possibility that both aspects of the birds'
      sensory experience during learning are reflected in properties of AF neurons.

PMID- 9236253
TI  - Stress and dominance in a social fish.
AB  - Many aspects of reproductive physiology are subject to regulation by social
      interactions. These include changes in neural and physiological substrates of
      reproduction. How can social behavior produce such changes? In experiments
      reported here, we manipulated the social settings of teleost fish and measured
      the effect (1) on stress response as reflected in cortisol production, (2) on
      reproductive potential as measured in production of the signaling peptide,
      gonadotropin-releasing hormone, and (3) on reproductive function measured in
      gonad size. Our results reveal that the level of the stress hormone cortisol
      depends critically on both the social and reproductive status of an individual
      fish and on the stability of its social situation. Moreover, the reproductive
      capacity of an individual fish depends on these same variables. These results
      show that social encounters within particular social contexts have a profound
      effect on the stress levels as well as on reproductive competence. Social
      behavior may lead to changes in reproductive state through integration of
      cortisol changes in time. Thus, information available from the stress pathway may
      provide socially relevant signals to produce neural change.

PMID- 9236254
TI  - Stimulation on the positive phase of hippocampal theta rhythm induces long-term
      potentiation that can Be depotentiated by stimulation on the negative phase in
      area CA1 in vivo.
AB  - Long-term potentiation (LTP) of synaptic transmission induced by high-frequency
      stimulation (HFS) is considered to be a model for learning processes; however,
      standard HFS protocols consisting of long trains of HFS are very different from
      the patterns of spike firing in freely behaving animals. We have investigated the
      ability of brief bursts of HFS triggered at different phases of background theta
      rhythm to mimic more natural activity patterns. We show that a single burst of
      five pulses at 200 Hz given on the positive phase of tail pinch-triggered theta
      rhythm reliably induced LTP in the stratum radiatum of the hippocampus of
      urethane-anesthetized rats. Three of these bursts saturated LTP, and 10 bursts
      occluded the induction of LTP by long trains of HFS. Burst stimulation on the
      negative phase or at zero phase of theta did not induce LTP or long-term
      depression. In addition, stimulation with 10 bursts on the negative phase of
      theta reversed previously established LTP. The results show that the phase of
      sensory-evoked theta rhythm powerfully regulates the ability of brief HFS bursts
      to elicit either LTP or depotentiation of synaptic transmission. Furthermore,
      because complex spike activity of approximately five pulses on the positive phase
      of theta rhythm can be observed in freely moving rats, LTP induced by the present
      theta-triggered stimulation protocol might model putative synaptic plastic
      changes during learning more closely than standard HFS-induced LTP.

PMID- 9236255
TI  - Regeneration of a central synapse restores nonassociative learning.
AB  - Sensitization is a form of nonassociative learning in which a strong or noxious
      stimulus persistently enhances the response produced by a weaker stimulus. In the
      leech Hirudo medicinalis, the S-interneuron is required for sensitization of the
      shortening response. A single S-cell axon was surgically separated from its sole
      synaptic partner, the neighboring S-cell. This consistently eliminated
      sensitization without impairing reflexive shortening itself, as measured in semi
      intact specimens. Sensitization of the shortening reflex returned after 3 weeks
      when the severed axon grew and regenerated its specific electrical synapse within
      the nerve cord, as shown by restored conduction of impulses between S-cells. This
      confirms the essential role of one neuron, the S-cell, in sensitization, and it
      demonstrates that regeneration of the synapse between S-cells restores this
      example of nonassociative learning.

PMID- 9236256
TI  - Low-frequency stimulation of afferent Adelta-fibers induces long-term depression
      at primary afferent synapses with substantia gelatinosa neurons in the rat.
AB  - Impulses in primary afferent nerve fibers may produce short- or long-lasting
      modifications in spinal nociception. Here we have identified a robust long-term
      depression (LTD) of synaptic transmission in substantia gelatinosa neurons that
      can be induced by low-frequency stimulation of primary afferent Adelta-fibers.
      Synaptic transmission between dorsal root afferents and neurons in the substantia
      gelatinosa of the spinal cord dorsal horn was examined by intracellular recording
      in a transverse slice dorsal root preparation of rat spinal cord. Conditioning
      stimulation of dorsal roots with 900 pulses given at 1 Hz (10 V, 0.1 msec)
      produced LTD of EPSP amplitudes in substantia gelatinosa neurons to 41 +/- 10% of
      control that lasted for at least 2 hr. When A- and C-fibers were recruited,
      conditioning stimulation was as effective as A-fiber stimulation alone. After
      LTD, synaptic strength could be increased to its original level by applying a
      second, high-frequency tetanic stimulus to the dorsal root, indicating that LTD
      is reversible and not attributable to damage of individual synapses. Bath
      application of the GABAA receptor antagonist bicuculline and glycine receptor
      antagonist strychnine did not affect LTD. When NMDA receptors were blocked by
      bath application of D-2-amino-5-phosphonovaleric acid, LTD was abolished or
      strongly reduced. Loading substantia gelatinosa neurons with Ca2+ chelator BAPTA
      also blocked or reduced LTD. After incubation of slices with calyculin A, a
      selective and membrane permeable inhibitor of protein phosphatases 1 and 2A, LTD
      was not attenuated. We propose that this form of LTD may be relevant for long
      lasting segmental antinociception after afferent stimulation.

PMID- 9236257
TI  - Bone density and body composition in Japanese women.
AB  - Total body bone mineral content (BMCTB in g) and density (BMDTB in g/cm2) and
      body composition were measured in 1006 healthy Japanese women aged 20-79 years
      using dual X-ray absorptiometry. Peak BMDTB was 1.11 +/- 0.05 g/cm2 in women 20
      49 years, and mean BMDTB was 1. 019 g/cm2 in the 6th decade, 0.956 g/cm2 in the
      7th decade, and 0. 900 g/cm2 in the 8th decade. BMDTB declined by 0.007
      g/cm2/year in women after age 50. This age-related decline in BMD showed a
      similar pattern to that seen for the lumbar spine and femoral neck, but the
      actual rate of loss was lower for BMDTB than for these other measurement sites.
      There was no significant difference between a eumenorrheic premenopausal group
      and a group with irregular menses. BMCTB and BMDTB were associated with body
      build, lean tissue mass, and fat mass (r = 0.29 approximately 0.65 and 0.26
      approximately 0.41, respectively). Bone mass and density decreased significantly
      in older women of all body builds. Premenopausal Japanese women had a 5% lower
      BMDTB than U.S. and European whites, but the difference was several times greater
      in postmenopausal than in premenopausal women.

PMID- 9236258
TI  - Spinal trabecular bone loss and fracture in American and Japanese women.
AB  - This study examined trabecular bone mineral density (BMD) in Japanese women with
      and without spinal fracture, and compared the results to American women with and
      without fracture. The quantitative computed tomography (QCT) systems used at the
      University of California, San Francisco (UCSF) and at Nagasaki University were
      cross-calibrated. Normative BMD was assessed with the K2HPO4 liquid phantom in
      538 Americans aged 20-85 years, and with the B-MAS200 phantom in 577 Japanese
      aged 20-83 years. These BMD were adjusted for use with the Image Analysis solid
      phantom using the result of cross-calibration. The trabecular BMD in 111
      postmenopausal American women (55 with fracture), and in 185 postmenopausal
      Japanese women (67 with fracture) were compared for investigation of the
      difference in BMD values relative to fracture status. The absolute BMD values in
      Japanese were lower than those in Americans, and the differences were greater
      with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1
      mg/cm3 in women aged 20-24 years, 40-44 years, 60-64 years, respectively. In
      premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas
      the peak bone mass was maintained until the age of 35 in the American women. In
      immediate postmenopausal women, BMD significantly decreased in both populations.
      In later postmenopausal women, BMD significantly decreased with age in the
      Japanese women but decreased less rapidly in the American women. The aging
      decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American
      and Japanese women, respectively. The fracture threshold is considered to be
      lower in Japanese women. However, the BMD difference between American and
      Japanese women with fracture was similar to that without fracture. The Z-scores
      of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese
      women. In conclusion, Japanese women were found to have a lower BMD and lower
      fracture threshold than American women. The significant decrease of spinal
      trabecular BMD in late postmenopause is potentially responsible for the higher
      prevalence of spinal fracture in Japanese women.

PMID- 9236259
TI  - Reduced bone mass and fat-free mass in women with multiple sclerosis: effects of
      ambulatory status and glucocorticoid Use.
AB  - Multiple sclerosis (MS) is associated with reduced bone mass and vitamin D
      deficiency. The underlying pathophysiology of the bone disease is uncertain,
      however, acute and long-term glucocorticoid use, progressive immobilization,
      vitamin D deficiency, and possibly skeletal muscle atrophy are likely to be
      determinants. The aims of this study were to determine (a) whether multiple
      sclerosis is associated with reduced fat-free mass and (b) whether in patients
      with multiple sclerosis, ambulation ability or glucocorticoid use is associated
      with bone mass and/or fat-free mass. Seventy-one female patients with MS were
      compared with 71 healthy, age-matched female controls. Total body bone mineral
      content (TBBMC, kg), fat mass (FM, kg), and fat-free mass (FFM, kg) were measured
      using dual X-ray absorptiometry. Disability status was graded according to the
      Kurtzke Expanded Disability Status Scale (EDSS) as ambulatory, with or without
      aide (EDSS score of 0 to 6.5), or predominantly wheelchair bound (EDSS score >
      6.5). The patients with MS, when compared to age-comparable controls, had
      deficits in TBBMC ( approximately 8%, -0.3 +/- 0.1 SD, P < 0.04) and FFM (
      approximately 5%, -0.3 +/- 0.1 SD, P < 0.01). Both TBBMC and FFM were negatively
      associated with EDSS score (r = 0.33, P < 0.01, and r = 0.41, P < 0.01,
      respectively). Patients with MS who were nonambulatory had even greater deficits
      in TBBMC and FFM as compared with age-matched controls (-0.6 +/- 0.1 SD, P <
      0.01, and -0.6 +/- 0. 1 SD, P < 0.01, respectively). By contrast, as compared
      with age-comparable controls, ambulatory patients with MS had no deficits in bone
      mass or soft tissue mass. When compared with ambulatory patients with MS,
      nonambulatory patients with MS had deficits in TBBMC and FFM (P < 0.01 and P <
      0.01, respectively). The difference in TBBMC was largely caused by the difference
      in fat-free mass, whereas the difference in FFM was largely caused by the
      difference in glucocorticoid use based on analysis of covariance. We conclude
      that in patients with multiple sclerosis, physical disuse is the main determinant
      for the reduction in bone mass. Glucocorticoid treatment is the major determinant
      of the reduction in fat-free mass and thus also contributes to the reduction in
      bone mass.

PMID- 9236260
TI  - Influence of body mass index on the age-related slope of total and regional bone
      mineral content.
AB  - The influence of body mass index (BMI) on T scores for total body bone mineral
      content (TBBMC) and regional bone mineral content (RBMC) was studied in 186
      healthy women: 100 postmenopausal, 35 perimenopausal, and 51 premenopausal. The
      three groups were divided by BMI >25 kg/m2 and BMI <25 kg/m2 and the
      postmenopausal women were further subdivided by years since menopause (YSM): <10,
      10-20, and >20. Tartrate-resistant acid phosphatase (TRAP) concentration was
      higher in perimenopausal and postmenopausal women with BMI <25 kg/m2 (P < 0.001).
      T scores for TBBMC and for axial or peripheral RBMC differed (P < 0.05 in all)
      between women with BMI >25 kg/m2 and BMI <25 kg/m2. The rate of perimenopausal
      and postmenopausal age-related slope of BMC, as reflected in all measurements,
      differed with BMI. In the overall group of women, the T score for TBBMC
      correlated significantly with BMI (r = 0.46, P < 0.0001); this correlation
      increased when adjusted for age (r = 0.62, P < 0.0001). BMI correlated with TRAP
      only in postmenopausal women (r = 0.57, P < 0. 0001). Yearly TBBMC decline was
      twice as high in postmenopausal women with BMI <25 kg/m2 (P = 0.0004) than in
      those with BMI >25 kg/m2; the decline of trunk RBMC was more significant (P <
      0.0001). These findings confirm the influence of BMI and gonadal status on bone
      mass.

PMID- 9236262
TI  - A double blind, placebo-controlled trial of ipriflavone for prevention of
      postmenopausal spinal bone loss.
AB  - One hundred ninety-eight postmenopausal women (aged 50-65 years) with vertebral
      bone density (VBD) 1 SD below the mean value for normal, age-matched,
      postmenopausal subjects were enrolled in six Italian centers and 134 completed 2
      years of treatment. All subjects were randomly allocated to a 2-year treatment
      with oral ipriflavone (200 mg t.i.d.) or a matching placebo, according to a
      double-blind, parallel group design. All patients also received an oral daily
      calcium supplement of 1 g as calcium carbonate. VBD and markers of bone turnover
      were measured at baseline, and every 6 months. A complete routine analysis of
      liver and kidney functions along with hematological parameters were measured
      before and at the end of treatment period. The valid completers analysis showed a
      significant increase of VBD in ipriflavone-treated women with average percent
      changes of +1.4 after 1 year, and +1% at the end of treatment period (P < 0.05).
      The placebo group presented a significant decrease of VBD after 2 years of
      treatment (P < 0.05). The difference between treatments was significant (P <
      0.01). The intention to treat analysis confirmed the significant decrease of VBD
      in the placebo group, with no changes in ipriflavone-treated women. Skeletal ALP
      significantly decreased in ipriflavone-treated women (P < 0.05). Serum BGP and
      urine HOP/Cr showed a significant decrease only in ipriflavone-treated women,
      suggesting an inhibitory effect on bone turnover rate. Adverse reactions, mainly
      gastrointestinal, occurred to a similar extent in the two treatment groups. The
      evaluation of patients' compliance, assessed by residual tablets count, revealed
      a drug intake of more than 80% after 2 years in 92.5% and 92.8% of patients
      treated with ipriflavone or placebo, respectively. This study demonstrates that
      ipriflavone can prevent bone loss in postmenopausal women with low bone mass.

PMID- 9236261
TI  - Influence of bone quality on precision of calcaneal ultrasonometry.
AB  - This study was designed to determine the changes in precision of the ultrasound
      parameters speed of sound (SOS), broadband ultrasound attenuation (BUA), and
      stiffness index (SI) as a function of bone quality. The instrument used in this
      investigation was the LUNAR Achilles. Of the 608 female patients who had paired
      measurements with repositioning, 200 had t scores >/=-1 and 408 had t scores </=
      2.5, thus rendering a normal and a grossly abnormal group for comparison of
      precision results. It was found that the median precision error (CV%) for BUA was
      1.99% for normal bone and 1.44% for abnormal bone (P = 0.02). No significant
      difference was obtained between median precision errors in normal and abnormal
      bone for the parameters SOS and SI, which were 0.23% and 0.19%, and 2.15% and
      2.02%, respectively. In the interquartile range, the mean precision errors for
      SOS and BUA were significantly different in normal and abnormal bone: SOS was
      0.25% and 0.21%, respectively, and BUA was 2. 31% and 1.85%, respectively. No
      significant change was registered for SI. Precision error appears to decrease
      slightly at lower values for calcaneal variables.

PMID- 9236263
TI  - Effect of clodronate on calcidiol serum levels in women with breast cancer.

PMID- 9236264
TI  - Clodronate prevents bone loss in aged ovariectomized rats.
AB  - The purpose of this study was to investigate the ability of clodronate to prevent
      ovariectomy (OVX)-induced osteopenia in aged rats. Fourteen-month-old female
      Sprague-Dawley rats (n = 166) were randomized into six groups. One group was
      sacrificed at the start of the study, four groups were ovariectomized, and one
      group was sham-operated (Sham). The OVX rats were given subcutaneously either
      vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3
      months, and the Sham rats were given the vehicle. At all dose levels clodronate
      inhibited trabecular bone loss in the distal femur and in the fourth lumbar
      vertebral body (L4), and decreased bone resorption as evidenced by urinary
      deoxypyridinoline excretion. The lowest dose of clodronate preserved serum
      osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the
      level of the Sham/veh group. The OVX-induced increase in periosteal bone
      formation of femoral diaphysis was unaffected by two smaller doses of clodronate,
      but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg
      clodronate, the percentage of femoral cortical bone area and the mean relative
      cortical thickness were higher compared with the OVX/veh group. There was a good
      positive correlation between the maximum load in three-point bending of the tibia
      and tibial ash weight. Normal lamellar pattern of newly formed cancellous and
      cortical bone was found after clodronate treatment. No signs of adverse
      accumulation of osteoid or any deleterious effect on mechanical strength of long
      bones and lumbar vertebrae were found.

PMID- 9236265
TI  - Effects of clodronate on cortical and trabecular bone in ovariectomized rats on a
      low calcium diet.
AB  - The aim of this study was to evaluate the contribution of a low calcium diet to
      the cortical and trabecular osteoporosis seen in ovariectomized rats after 7
      weeks on a low calcium diet and to investigate the effects of the bisphosphonate
      clodronate on this development of osteoporosis. Thirty-six mature, female Wistar
      rats were randomized into four groups: Ovx-B (bisphosphonate) and Ovx-C (control)
      were ovariectomized, and Sham-Ca (low calcium) and Sham+Ca (normal calcium) were
      sham operated. The first three groups were fed a low calcium diet (0.01%) and
      Sham+Ca normal rat chow (Ca 1.1%). The Ovx-B received 10 mg/kg s.c. clodronate
      daily for nine weeks, and Ovx-C, Sham-Ca, and Sham+Ca received the same volumes
      of saline. Bone mineral turnover measured as 85Sr-uptake was increased in all low
      calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and
      ash weight than the other groups, and Ovx-C had higher dry weight compared with
      Ovx-B and Sham-Ca. Calcium content was lower in both Ovx groups compared to both
      Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in
      Ovx-B compared with Ovx-C. In the femoral shaft, Sham+Ca had significantly higher
      ultimate bending moment, energy absorption, and deflection compared to the other
      three groups. Ultimate bending moment was higher in Sham-Ca than in Ovx-C.
      Stiffness was increased in both Sham+Ca and Ovx-B compared to Ovx-C. The maximum
      stress in the femoral midshaft was higher in Sham+Ca than in the other groups,
      and higher in Ovx-B than in Ovx-C. Histomorphometry showed increased medullary
      area in all low calcium groups compared to Sham+Ca and larger cortical area in
      Sham+Ca and Ovx-B compared to Ovx-C. Compared to Sham+Ca the trabecular bone
      volume was decreased to 30% in Sham-Ca and to 9% in Ovx-C, but was unchanged in
      Ovx-B. The low calcium diet generally increased bone mineral turnover and reduced
      the tibial bone volume. Femoral changes led to a reduction of cortical fracture
      strength and maximal stress. Ovariectomy in addition to a low calcium diet
      reduced femoral strength even more. Daily injections of clodronate to
      ovariectomized rats on a low calcium diet increased femoral shaft stiffness and
      maximum stress, and clodronate preserved both trabecular and cortical tibial bone
      volume completely.

PMID- 9236266
TI  - Does colchicine really induce bone formation in the rodent bone marrow?
AB  - Intravenous injection of a single dose of colchicine into inbred strains of
      BALB/c and CFW/L1 mice and into WAG rats did not effect rapid intramedullar bone
      formation and resorption, as has been claimed by the research group from Tokyo
      Medical and Dental University [14-17]. The applied doses of colchicine arrested
      metaphase during the first 4 hours postadministration and were noxious for
      hemopoietic tissue (necrosis of bone marrow was evident in 2 and 4 day
      specimens), but on longitudinal, serial sections of long bones there was no
      evidence of stimulation of osteogenesis at any point in time (2-26-day
      specimens). It is postulated that the system of ectopic osteogenesis by
      colchicine injection is not reproducible in mice and WAG rats, and the apparently
      osteogenic effect of colchicine, observed by the Ogura group [14-17], was
      mistakenly described as congenital osteopetrosis.

PMID- 9236267
TI  - Acute effects of ethanol on mineral metabolism and trabecular bone in Sprague
      Dawley rats.
AB  - In order to assess the effects of acute ethanol intoxication on bone, 45 female
      Sprague-Dawley rats were studied. Five rats were sacrificed at baseline. The
      remainder received either ethanol (2 g/kg of body weight) intraperitoneally or
      isotonic saline. Rats were sacrificed in groups of 10 (5 intoxicated and 5
      placebo) at 1, 4, 8, and 24 hours after injection. At the time of sacrifice, a
      blood sample was obtained and the 4th vertebra was excised for histomorphometric
      analysis of undecalcified bone. Effect of ethanol was assessed by an analysis of
      variance test using a Scheffe procedure. In ethanol-treated rats we observed
      (mean +/- SD, ethanol versus controls, maximum difference point, P value) a
      significant decrease in osteiod surface with osteoblasts (42.86 +/- 15.61% versus
      64.57 +/- 6.24%, P < 0.05); osteoclast number (0.05 +/- 0.02 n/mm2 versus 0.17 +/
      0.09 n/nm2, P < 0.05), and osteocalcin (36.9 +/- 2.21 ng/ml versus 45.8 +/- 5.1
      ng/ml, P < 0.05). Osteoclast surface was initially reduced (0.129 +/- 0.09%
      versus 0.425 +/- 0. 26%, P < 0.01) but showed a subsequent increase (0.765 +/-
      0.24% versus 0.226 +/- 0.17%, P < 0.01) attributable to alcohol. There was also a
      significant decrease in serum Ca (8.51 +/- 0.23 mg/dl versus 9.10 +/- 0.29 mg/dl,
      P < 0.01) and parathyroid hormone values (23.51 +/- 5.72 pg/ml versus 76.39 +/-
      11.66 pg/ml, P < 0.001). We conclude that acute alcohol intoxication in rats
      induces early striking changes in bone histology and analytical parameters, not
      completely reversed after 24 hours. These data are consistent with a toxic effect
      induced by alcohol on bone.

PMID- 9236268
TI  - Polyphyletic gene losses can bias backtrack characterizations of the cenancestor.

PMID- 9236270
TI  - Use of a deviant mitochondrial genetic code in yellow-green algae as a landmark
      for segregating members within the phylum.
AB  - Several algae that were previously classified in the phylum Xanthophyta (yellow
      green algae) were assigned in 1971 to a new phylum, Eustigmatophyta. It was
      anticipated that the number of algae reclassified to Eustigmatophyta would
      increase. However, due to the fact that the morphological characteristics that
      segregate eustigmatophytes from other closely related algae can be only obtained
      through laborious electron microscopic techniques, the number of members in this
      phylum have increased rather slowly. We attempted, therefore, to segregate two
      closely related groups of algae, eustigmatophytes and yellow-green algae, on the
      basis of a molecular phylogenetic tree as a means of providing an alternative
      method of distinguishing these phyla. We analyzed the mitochondrial cytochrome
      oxidase subunit I (COXI) gene sequences of eight algae classified as
      xanthophyceans and found that six manifested the expected deviant genetic code
      where AUA codes for methionine (AUA/Met), but not for isoleucine (AUA/Ile) as in
      the universal genetic code. The other two, Monodus sp. (CCMP 505) and Ophiocytium
      majus (CCAP 855/1), which were presumed to be yellow-green algae, and all the
      examined eustigmatophytes utilized AUA for Ile. In addition, the phylogenetic
      tree of COXI gene sequences showed that the six yellow-green algae bearing the
      AUA/Met deviant code composed a tight clade with a bootstrap value of 100%. The
      phylogenetic tree of the corresponding sequences from Monodus sp. and Ophiocytium
      majus and the eustigmatophytes also composed a tight cluster, but with a
      bootstrap value of 92%. These results strongly suggest that two previously
      classified members of yellow-green algae belong to the phylum Eustigmatophyta.
      Therefore, examination of the mitochondrial genetic code in algae appears to be a
      potentially very useful genetic marker for classifying these organisms,
      especially when it is considered with the results obtained through a molecular
      phylogenetic tree.

PMID- 9236271
TI  - Comparative evolutionary rates of introns and exons in murine rodents.
AB  - Analysis of DNA sequences of 132 introns and 140 exons from 42 pairs of
      orthologous genes of mouse and rat was used to compare patterns of evolutionary
      change between introns and exons. The mean of the absolute difference in length
      (measured in base pairs) between the two species was nearly five times as high in
      the case of introns as in the case of exons. The average rate of nucleotide
      substitution in introns was very similar to the rate of synonymous substitution
      in exons, and both were about three times the rate of substitution at
      nonsynonymous sites in exons. G+C content of introns and exons of the same gene
      were correlated; but mean G+C content at the third positions of exons was
      significantly higher than that of introns or positions 1-2 of exons from the same
      gene. G+C content was conserved over evolutionary time, as indicated by strong
      correlations between mouse and rat; but the change in G+C content was greatest at
      position 3 of exons, intermediate in introns, and lowest at positions 1-2 in
      introns.

PMID- 9236272
TI  - Horizontal transfer of genes coding for the photosynthetic reaction centers of
      purple bacteria.
AB  - Phylogenetic trees were drawn and analyzed based on the nucleotide sequences of
      the 1.5-kb gene fragment coding for the L and M subunits of the photochemical
      reaction center of various purple photosynthetic bacteria. These trees are mostly
      consistent with phylogenetic trees based on 16S rRNA and soluble cytochrome c,
      but differ in some significant details. This inconsistency implies horizontal
      transfer of the genes that code for the photosynthetic apparatus in purple
      bacteria. Possibilities of similar transfers of photosynthesis genes during the
      evolution of photosynthesis are discussed especially for the establishment of
      oxygenic photosynthesis.

PMID- 9236273
TI  - Characterization of the Sol3 family of nonautonomous transposable elements in
      tomato and potato.
AB  - Sol3 transposons are mobile elements defined by long terminal inverted repeats
      which are found in tomato and potato. Members of the Sol3 family have been
      isolated from a variety of solanaceous species including Solanum tuberosum
      (potato), S. demissum, S. chacoense, Lycopersicon esculentum (tomato), and L.
      hirsutum. While highly conserved elements are found within different species,
      Sol3 terminal inverted repeats can also flank unrelated sequences. Southern blot
      analysis indicates that Sol3 elements are less prevalent in the potato
      (approximately 50 copies) than in the tomato (>100 copies) genome. No Sol3
      hybridizing sequences were observed in tobacco. While a number of Sol3 elements
      ranging in size from 500 bp to 2 kbp were sequenced, no transposase coding
      domains could be identified within the internal regions of the elements. The data
      suggest that the Sol3 represent a heterogeneous family of nonautonomous
      transposable elements associated with an as-yet-unidentified autonomous
      transposon.

PMID- 9236274
TI  - Intragenomic distribution and stability of transposable elements in euchromatin
      and heterochromatin of Drosophila melanogaster: non-LTR retrotransposon.
AB  - The intragenomic location of the elements of the I, G, jockey, F, and Doc
      transposon families has been studied by the Southern blot analysis, in 12
      laboratory Drosophila melanogaster stocks. Elements located in euchromatin,
      heterochromatin, and on the Y chromosome are identified, and their stability has
      been assessed by comparing the autoradiographs detected in different stocks and
      analysis of individual flies. Evidence is shown suggesting that preferential
      location in euchromatin or heterochromatin and the distribution within
      heterochromatin are distinctive of transposon families. Elements located in
      heterochromatin can be unstable. These results are discussed in the context of
      the relationship between transposable elements and the host genome.

PMID- 9236275
TI  - Sequence diversity and molecular evolution of the merozoite surface antigen 2 of
      Plasmodium falciparum.
AB  - Eleven new alleles of the Plasmodium falciparum merozoite surface antigen 2
      (MSA2) from Papua New Guinea were analyzed by direct sequencing of polymerase
      chain reaction (PCR) products. We have used the sequence information to trace the
      molecular evolution of MSA2. The repeats of ten alleles belonging to the 3D7
      allelic family differed considerably in size, nucleotide sequence, and repeat
      copy number. In the repeat region of these new alleles, codon usage was extremely
      biased with an exclusive use of NNT codons. Another new allele sequenced belonged
      to the FC27 family and confirmed the family-specific conserved structure of 96
      and 36 bp repeats. In order to assess sequence microheterogeneity within samples
      defined as the same genotype by restriction fragment length polymorphism (RFLP),
      we have analyzed single-strand conformation polymorphism (SSCP) of different
      samples of the most frequent allele (D10 of the FC27 family) in the study
      population. No sequence heterogeneity could be detected within the repeat region.
      Based on analysis of the repeat regions in both allelic families, we discuss the
      hypothesis of a different evolutionary strategy being represented by each of the
      allelic families. Kew words: Merozoite surface antigen 2 - Nucleotide sequence
      comparisons - Molecular evolution

PMID- 9236276
TI  - Matrix multiplication with DNA.
AB  - A DNA-based method for calculating the product of Boolean matrices or matrices
      containing positive, real numbers is presented. In the case of matrices
      containing real numbers, the manipulation of reaction conditions allows a
      quantitative calculation to be performed. The use of DNA to perform an analog
      calculation illustrates a new approach to computing with DNA.

PMID- 9236277
TI  - Ribosomal DNA ITS-1 and ITS-2 sequence comparisons as a tool for predicting
      genetic relatedness.
AB  - The determination of the secondary structure of the internal transcribed spacer
      (ITS) regions separating nuclear ribosomal RNA genes of Chlorophytes has improved
      the fidelity of alignment of nuclear ribosomal ITS sequences from related
      organisms. Application of this information to sequences from green algae and
      plants suggested that a subset of the ITS-2 positions is relatively conserved.
      Organisms that can mate are identical at all of these 116 positions, or differ by
      at most, one nucleotide change. Here we sequenced and compared the ITS-1 and ITS
      2 of 40 green flagellates in search of the nearest relative to Chlamydomonas
      reinhardtii. The analysis clearly revealed one unique candidate, C. incerta.
      Several ancillary benefits of the analysis included the identification of
      mislabelled cultures, the resolution of confusion concerning C. smithii, the
      discovery of misidentified sequences in GenBank derived from a green algal
      contaminant, and an overview of evolutionary relationships among the Volvocales,
      which is congruent with that derived from rDNA gene sequence comparisons but
      improves upon its resolution. The study further delineates the taxonomic level at
      which ITS sequences, in comparison to ribosomal gene sequences, are most useful
      in systematic and other studies.

PMID- 9236278
TI  - A theoretical method for evaluating the relative importance of positive selection
      and neutral drift from observed base changes.
AB  - To evaluate the relative importance of positive selection and neutral drift from
      the nucleotide base changes observed in the homologous alignment of genes, a
      theoretical equation of base changes is formulated by including both the
      influence of selection and the base substitutions due to mutations. Under the
      assumption that the average rate of base substitutions estimated from synonymous
      changes is the "true" mutation rate applicable at all positions, this method is
      applied to the vertebrate globin gene family, and evaluates the departures of
      base change rates from the "true" mutation rate at the first and second codon
      positions as a consequence of preferential selection for the conservation of
      important function. In addition to the strong effect of selection on the amino
      acid residues in the internal region mostly common to myoglobin and hemoglobin
      chains, the distinctive directions of selective parameter values are seen at
      sites on the globin surface, distinguishing the subunit contact residues of
      hemoglobins from the polar residues on the surface of myoglobins. Moreover, this
      effect of selection distinguishing between the myoglobin and hemoglobin chain
      genes becomes weaker in cold-blooded vertebrates, especially in fish, strongly
      suggesting the possibility that the clear distinction between these globins is a
      result of selection out of the changes regarded as neutral ones in an ancestor of
      vertebrates. Thus, the present method may also serve to investigate the homology
      of many other proteins from the aspect of molecular evolution, mainly focusing on
      the evolution of their biological functions.

PMID- 9236281
TI  - FORUM: Dynamics and Causation of Environmental Equity, Locally Unwanted Land
      Uses, and Neighborhood Changes
AB  - / Why are some environmental risks distributed disproportionately in the
      neighborhoods of the minorities and the poor? A hypothesis was proposed in a
      recent study that market dynamics contributed to the current environmental
      inequity. That is, locally unwanted land uses (LULUs) make the host communities
      home to more poor people and people of color. This hypothesis was allegedly
      supported by a Houston case study, whereby its author analyzed the postsiting
      changes of the socioeconomic characteristics of the neighborhoods surrounding
      solid waste facilities. I argue that such an analysis of postsiting changes alone
      is insufficient to test the causation hypothesis. Instead, I propose a conceptual
      framework for analysis of environmental equity dynamics and causation. I suggest
      that the presiting neighborhood dynamics and the characteristics of control
      neighborhoods be analyzed as the first test for the causation hypothesis.
      Furthermore, I present theories of neighborhood change and then examine
      alternative hypotheses that these theories offer for explaining neighborhood
      changes and for the roles of LULUs in neighborhood changes. These alternative
      hypotheses should be examined when analyzing the relationship between LULUs and
      neighborhood changes in a metropolitan area. Using this framework of analysis, I
      revisited the Houston case. First, I found no evidence that provided support for
      the hypothesis that the presence of LULUs made the neighborhoods home to more
      blacks and poor people, contrary to the conclusion made by the previous study.
      Second, I examined alternative hypotheses for explaining neighborhood changes
      invasion-succession, other push forces, and neighborhood life-cycle; the former
      two might offer better explanation.KEY WORDS: Environmental equity and justice;
      Locally unwanted lane uses; Siting; Market dynamics; Invasion-succession;
      Neighborhood changes

PMID- 9236282
TI  - PROFILE: Integrated Management to Create New Breeding Habitat for Dalmatian
      Pelicans (Pelecanus crispus) in Greece
AB  - / An integrated management plan to create favorable nesting habitat for the world
      endangered Dalmatian pelicans, was tested at Kerkini irrigation reservoir, a
      Ramsar wetland. The lake is the major wintering site of Dalmatian pelicans in
      Europe, where the species lives year-round without breeding. The rise of water
      level at the reservoir during spring (exceeding 5 m) has an impact on the whole
      system, including several birds, which lose their nesting habitat. Although the
      integrity of the wetland demands ecological restoration with changes in its
      hydrologic regime, local socioeconomic conditions allow only habitat level
      interventions. During the planning phase of the management plan, both the
      ecological and social context of the interventions were considered. Monitoring of
      all pelican habitats and populations provided the scientific basis, while a
      socioecological survey on knowledge/attitudes of local fishermen toward wetland
      identified conflicts with specific resources and planned management. To gain
      public support, a broad information/education program was implemented. The
      education program for fishermen was based on the findings of the socioecological
      survey. The in situ management involved experimental construction of floating
      rafts, platforms over water, dredged-spoil islands, and platforms at various
      sites of the wetland. Monitoring of the managed habitats showed that most
      waterbirds used them for resting and roosting. Common terns nested on the rafts,
      cormorants on the platforms, and Dalmatian pelicans on the man-made island. Under
      the prevailing hydrologic and weather conditions, islands seem to be the most
      suitable habitat for pelican nesting. It is concluded that wildlife habitat
      management should integrate the ecological component, related to the needs of the
      species and ecosystem, with the social one, expressed by cooperation and
      involvement of the local community.KEY WORDS: Integrated management; Pelican;
      Nesting habitat; Habitat management; Reservoir-wetland; Public participation,
      Greece

PMID- 9236279
TI  - The sequences of heat shock protein 40 (DnaJ) homologs provide evidence for a
      close evolutionary relationship between the Deinococcus-thermus group and
      cyanobacteria.
AB  - The genes encoding for heat shock protein 40 (Hsp40 or DnaJ) homologs were cloned
      and sequenced from the archaebacterium Halobacterium cutirubrum and the
      eubacterium Deinococcus proteolyticus to add to sequences from the gene banks.
      These genes were identified downstream of the Hsp70 (or DnaK) genes in genomic
      fragments spanning this region and, as in other prokaryotic species, Hsp70-Hsp40
      genes are likely part of the same operon. The Hsp40 homolog from D. proteolyticus
      was found to be lacking a central 204 base pair region present in H. cutirubrum
      that encodes for the four cysteine-rich domains of the repeat consensus sequence
      CxxCxGxG (where x is any amino acid), present in most Hsp40 homologs. The
      available sequences from various archaebacteria, eubacteria, and eukaryotes show
      that the same deletion is also present in the homologs from Thermus aquaticus and
      two cyanobacteria, but in no other species tested. This unique deletion and the
      clustering of homologs from the Deinococcus-Thermus group and cyanobacterial
      species in the Hsp40 phylogenetic trees suggest a close evolutionary relationship
      between these groups as was also shown recently for Hsp70 sequences (R.S. Gupta
      et al., J Bacteriol 179:345-357, 1997). Sequence comparisons indicate that the
      Hsp40 homologs are not as conserved as the Hsp70 sequences. Phylogenetic analysis
      provides no reliable information concerning evolutionary relationship between
      prokaryotes and eukaryotes and their usefulness in this regard is limited.
      However, in phylogenetic trees based on Hsp40 sequences, the two archaebacterial
      homologs showed a polyphyletic branching within Gram-positive bacteria, similar
      to that seen with Hsp70 sequences.

PMID- 9236283
TI  - Simulation of Halocarbon Production and Emissions and Effects on Ozone Depletion
AB  - / This paper describes an integrated model that simulates future halocarbon
      production/emissions and potential ozone depletion. Applications and historical
      production levels for various halocarbons are discussed first. A framework is
      then presented for modeling future halocarbon impacts incorporating differences
      in underlying demands, applications, regulatory mandates, and environmental
      characteristics. The model is used to simulate the potential impacts of several
      prominent issues relating to halocarbon production, regulation, and environmental
      interactions, notably: changes in agricultural methyl bromide use, increases in
      effectiveness of bromine for ozone depletion, modifications to the elimination
      schedule for HCFCs, short-term expansion of CFC demand in low use compliance
      countries, and delays in Russian Federation compliance. Individually, each issue
      does not unequivocally represent a significant likely increase in long-term
      atmospheric halogen loading and stratospheric ozone depletion. In combination,
      however, these impacts could increase peak halogen concentrations and long-term
      integral halogen loading, resulting in higher levels of stratospheric ozone
      depletion and longer exposure to increased levels of UV radiation.KEY WORDS:
      Halocarbons; Ozone depletion; Montreal Protocol; Integrated assessment

PMID- 9236285
TI  - Quantifying Targets for Rehabilitating Degraded Areas of the Great Lakes
AB  - / One attempt to quantify targets for rehabilitating degraded aquatic ecosystems
      has been through a United States-Canada program to develop and implement
      comprehensive remedial action plans (RAPs) to restore beneficial uses in 42 Great
      Lakes Areas of Concern. The International Joint Commission has facilitated
      agreement on listing/delisting guidelines for determining when use impairments
      exist in areas of concern and when uses have been restored, while
      federal/state/provincial governments and local stakeholders have provided
      leadership in establishing quantitative targets for restoring uses and in
      determining how to achieve them. The listing/delisting guidelines have been
      instrumental in helping reach agreement on problem definition (lack of agreement
      on problem definition has historically been used as a reason to delay action) and
      reaching agreement on quantitative targets for restoring uses. Quantitative,
      ecosystem-based targets are being used to drive the RAP process, help
      organizations pursue a common mission of restoring uses, and help achieve greater
      accountability. As a priority, the target-setting process must also recognize the
      importance of establishing both short- and long-term milestones in order to
      measure and celebrate incremental progress in restoring uses.KEY WORDS: Use
      impairments; Restoring uses; Quantitative targets

PMID- 9236284
TI  - Water Quality Functions of Riparian Forest Buffers in Chesapeake Bay Watersheds
AB  - / Maryland, Virginia, and Pennsylvania, USA, have agreed to reduce nutrient
      loadings to Chesapeake Bay by 40% by the year 2000. This requires control of
      nonpoint sources of nutrients, much of which comes from agriculture. Riparian
      forest buffer systems (RFBS) provide effective control of nonpoint source (NPS)
      pollution in some types of agricultural watersheds. Control of NPS pollution is
      dependent on the type of pollutant and the hydrologic connection between
      pollution sources, the RFBS, and the stream. Water quality improvements are most
      likely in areas of where most of the excess precipitation moves across, in, or
      near the root zone of the RFBS. In areas such as the Inner Coastal Plain and
      Piedmont watersheds with thin soils, RFBS should retain 50%-90% of the total
      loading of nitrate in shallow groundwater, sediment in surface runoff, and total
      N in both surface runoff and groundwater. Retention of phosphorus is generally
      much less. In regions with deeper soils and/or greater regional groundwater
      recharge (such as parts of the Piedmont and the Valley and Ridge), RFBS water
      quality improvements are probably much less. The expected levels of pollutant
      control by RFBS are identified for each of nine physiographic provinces of the
      Chesapeake Bay Watershed. Issues related to of establishment, sustainability, and
      management are also discussed.KEY WORDS: Riparian forest buffers; Chesapeake Bay;
      Nonpoint source pollution; Nitrogen; Phosphorus; Sediment

PMID- 9236286
TI  - RESEARCH: Are Recent Watershed Disturbances Associated with Temporal and Spatial
      Changes in Water Quality of Lake George, New York, USA?
AB  - / Lake George, a mesooligotrophic lake, is a historically important recreational
      site in northeastern New York, USA. A preliminary analysis of the data, collected
      during 1980-1990, suggested that the indicators of primary productivity have
      increased, particularly in the southern basin of the lake. This change was
      attributed to the recent increases in the urbanization and development of the
      southern shorelines. The suggestion of temporal and spatial degradation in
      lakewater quality has caused substantial concerns among the decision makers and
      the public alike. The main objective of this study is to evaluate possible
      eutrophication of the lake by quantification of temporal and spatial trends in
      concentrations of total phosphorus (TP), chlorophyll a (Chl a), silica (Si), and
      chloride (Cl) through the use of proper statistical techniques. Results indicate
      no statistically significant changes in the concentrations of TP, Chl a, or Si in
      the spring or summer from 1981 to 1993. A significant temporal trend of increase
      in Cl concentration is, however, detected. This is perhaps the strongest evidence
      that the development of the Lake George watershed has affected lakewater
      chemistry. In spring, the concentrations of TP, Chl a, Si, and Cl, averaged over
      all 13 years, were higher in the south basin, but differences are not
      statistically significant (i.e., P > 0.05). In summer, Si was slightly but
      significantly lower, and Cl was nonsignificantly higher in the south basin.
      Significant interactions between temporal and spatial changes are detected based
      only on summer values of TP and Chl a, indicating differential trends of change
      for these two variables in the south and north basins during the last 13
      years.KEY WORDS: Repeated-measures ANOVA; Split-plot design; Lakewater chemistry;
      Lake George

PMID- 9236287
TI  - The Importance of Contexts in Strategies of Environmental Organizations with
      Regard to Climate Change
AB  - / The purpose of the study was to investigate the extent to which strategies of
      environmental organizations depend on contexts. I examined this dependence by
      analyzing the strategies of five environmental organizations in the Netherlands
      with regard to climate change. These strategies were investigated over time and
      compared with the strategies these organizations had used in relation to ozone
      depletion and acidification. The results indicate that several of the
      organizations changed their strategies with respect to climate change over time.
      Furthermore, different strategies were used simultaneously in relation to the
      three problems. The findings suggest that strategies concerning climate change
      were to a considerable extent determined by the dominant framing of the problem
      in society. This framing was defined mainly by actors other than environmental
      organizations. The initial framing of climate change as a CO2 problem, which
      brought the issue into the energy debate, as well as the more general definition
      of the problem in the late 1980s as a greenhouse problem, were very important for
      determining the strategies of the organizations. It can be concluded that
      strategies of Dutch environmental organizations with regard to climate change
      were strongly dependent on the context.KEY WORDS: Environmental organization;
      Strategy; Climate change; Man-nature relationship; Problem definition; Context

PMID- 9236288
TI  - Environmental Awareness, Economic Orientation, and Farming Practices: A
      Comparison of Organic and Conventional Farmers
AB  - / This study examines similarities and differences between organic and
      conventional farmers. We explore the factors that underlie farmers' conservation
      attitudes and behaviors, including demographic and farm characteristics,
      awareness of and concern for environmental problems associated with agriculture,
      economic orientation toward farming, and self-reported conservation practices. A
      series of intensive personal interviews was conducted with 25 farmers in
      Washtenaw County, Michigan, USA, using both qualitative and quantitative survey
      methods. The findings indicate that both groups of farmers share a concern for
      the economic risks associated with farming, although the organic farmers reported
      a significantly greater concern for long-term sustainability and a greater
      willingness to incur present risk to gain future benefits. Organic farmers
      expressed a greater awareness of and concern for environmental problems
      associated with agriculture. Organic farmers also scored significantly higher on
      a multifaceted measure of conservation practices, although both groups had a
      fairly high adoption rate. Implications of these findings are discussed, relative
      to economic risks of farming, implications for new farmers, effectiveness of
      conservation education and government programs, and impact of farm size and crop
      diversity.KEY WORDS: Environmental attitudes; Conservation behaviors; Organic
      farming; Agricultural sustainability

PMID- 9236289
TI  - On the Issue of Functional Form Choice in Hedonic Price Functions: Further
      Evidence
AB  - / Historically, researchers applying the hedonic technique devoted little effort
      to testing alternative functional forms. This study used Box-Cox transformations
      on a hedonic model examining property value effects of a closed landfill to help
      select among alternative functional forms. Although this particular application
      found that a log-log functional form was appropriate, it appears that functional
      form may vary by problem and case study area selected. Benefit estimates
      generated using the hedonic technique may be substantial over- or underestimates
      if the incorrect functional form is chosen. Proximity to the landfill had no
      significant effect on property values.KEY WORDS: Hedonics; Functional form; Box
      Cox; Landfills

PMID- 9236290
TI  - Methods of Assessing and Achieving Normality Applied to Environmental Data
AB  - / It has been recognized for a long time that data transformation methods capable
      of achieving normality of distributions could have a crucial role in statistical
      analysis, especially towards an efficient application of techniques such as
      analysis of variance and multiple regression analysis. Normality is a basic
      assumption in many of the statistical methods used in the environmental sciences
      and is very often neglected. In this paper several techniques to test normality
      of distributions are proposed and analyzed. Confidence intervals and
      nonparametric tests are used and discussed. Basic and Box-Cox transformations are
      the suggested methods to achieve normal variables. Finally, we develop an
      application related to environmental data with atmospheric parameters and SO2 and
      particle concentrations. Results show that the analyzed transformations work well
      and are very useful to achieve normal distributions.KEY WORDS: Normal
      distribution; Kurtosis; Skewness; Confidence intervals; Box-Cox transformations;
      Nonparametric tests

PMID- 9236291
TI  - ENVIRONMENTAL AUDITING: Impoundment Productivity in the Prudhoe Bay Oil Field,
      Alaska: Implications for Waterbirds
AB  - / To evaluate impoundments as habitat for waterbirds, we compared impoundments
      and natural ponds in the Prudhoe Bay oil field, Alaska, from 1991 to 1993, with
      respect to macroinvertebrate productivity, phytoplankton biomass (chlorophyll a),
      and nutrient availability (phosphorus and nitrogen). High variability in these
      limnological characteristics, particularly among impoundments, obscured potential
      differences between impoundments and ponds. No significant differences were found
      in chlorophyll or nutrient concentrations, and in only two cases were there
      differences in invertebrate production: gastropods were significantly more
      abundant in impoundments than in ponds in June, and trichopterans were
      significantly more abundant in impoundments than in ponds in July. For
      comparisons within impoundments and ponds, there were significant differences in
      invertebrate abundance between habitats and between wetland types. For example,
      plecopterans, trichopterans, and gastropods (all taxa combined) were consistently
      more abundant in shallow-Arctophila impoundments and ponds than in shallow-Carex
      impoundments and ponds. Thus, ponds and impoundments may differ significantly in
      invertebrate production, but we lack information on the amount of different
      habitat types (i.e., center versus emergent vegetation, Carex versus Arctophila)
      used by these taxa within each water body type. It is a reasonable speculation,
      based on results of this study, that impoundments and ponds may have similar
      value as feeding habitat for invertebrate-eating waterbirds. Thus the presence of
      impoundments may be consistent with waterbird management goals on the Arctic
      Coastal Plain.KEY WORDS: Arctic impoundments; Production; Macroinvertebrates;
      Nutrients; Phytoplankton; Impact assessment

PMID- 9236292
TI  - Exploring Chemical Variables in Ligustrum lucidum Ait. F. Tricolor (Rehd.) Rehd.
      in Relation to Air Pollutants and Environmental Conditions
AB  - / A diagnostic study was done on Ligustrum lucidum Ait. f. tricolor (Rehd.) Rehd.
      in relation to atmospheric pollutants in Cordoba city, Argentina. The study area
      receives regional pollutants and was categorized taking into account traffic
      level, industrial density, type of industry, location of the sample point in
      relation to the street corner, treeless condition, and topographic level. Dried
      weight/fresh weight ratio (DW/FW) and specific leaf area (SLA) were calculated,
      and concentrations of chlorophylls, carotenoids, total sulfur, soluble proteins,
      malondialdehyde (MDA), and hydroperoxy conjugated dienes (HPCD) were determined
      in leaf samples. Sulfur content correlates positively with traffic density and
      SLA correlates negatively with some combinations of the categorical variables;
      MDA correlates positively with topographic level and total protein concentration
      correlates negatively with treeless condition. On the basis of our results,
      traffic, location of trees, type of industry, situation of a tree with respect to
      others, and topographic level are the environmental variables to bear in mind
      when selecting analogous sampling points in a passive monitoring program. An
      approximation to predict tree injury may be obtained by measuring DW/FW ratio,
      proteins, pigments, HPCD, and MDA as they are responsible for the major
      variability of data.KEY WORDS: L. lucidum Ait. f. tricolor (Rehd.) Rehd.; Air
      pollution; Sulfur accumulation; Pigments; Urban environment; Argentina

PMID- 9236293
TI  - Gene knockout of the intracellular amylase gene by homologous recombination in
      Streptococcus bovis.
AB  - Streptococcus bovis expresses two different amylases, one intracellular and the
      other secreted. A suicide vector containing part of the intracellular alpha
      amylase gene from Streptococcus bovis WI-1 was recombined into the S. bovis WI-1
      chromosome to disrupt the endogenous gene. Recombination was demonstrated by
      Southern blot, and zymogram analysis confirmed the loss of the intracellular
      amylase. Amylase activity in cell-free extracts of the recombinant grown in the
      presence of 1% starch was only 7% of wild type. The rate of logarithmic growth of
      the recombinant was 15-20% of the wild type in medium containing either 1%
      glucose, starch, or cellobiose. Revertants and non-amylase control recombinants
      had logarithmic growth rates that were the same as wild type. Plasmid
      transformants containing multiple copies of the cloned gene expressed up to
      threefold higher levels of intracellular amylase activity than wild type but did
      not demonstrate elevated growth rates. These results suggest that a critical
      level of expression of the intracellular amylase gene may be important for rapid
      growth of the bacterium.

PMID- 9236294
TI  - Isolation and characterization of LPS mutants of Actinobacillus pleuropneumoniae
      serotype 1.
AB  - The major adhesin of Actinobacillus pleuropneumoniae, the causative agent of
      porcine pleuropneumonia, has been previously identified as lipopolysaccharide
      (LPS). The purpose of the present study was to isolate and characterize A.
      pleuropneumoniae LPS mutants. Screening of LPS mutants was performed with colony
      dot and sensitivity to novobiocin. One mutant obtained by colony dot (F19) and
      one mutant selected for its increased sensitivity to novobiocin (33.1) did not
      react with a monoclonal antibody against A. pleuropneumoniae serotype 1 O-antigen
      compared with the parent strain. Mutants F19 and 33.1 did not express high
      molecular-mass LPS bands as determined in silver-stained SDS-PAGE gels. The core
      lipid A region of mutant 33.1 and of the parent strain had similar relative
      mobilities and reacted with serum from a pig experimentally infected with the
      serotype 1 reference strain of A. pleuropneumoniae, while the same region in
      mutant F19 showed faster migration and did not react with this serum. Use of
      piglet tracheal frozen sections indicated that mutant F19 was able to adhere to
      piglet trachea as well as the parent strain, while mutant 33.1 adhered [half as
      much as] the parent strain. Finally, both LPS mutants were markedly less virulent
      in mice than the parent strain. Taken together, our observations support the idea
      that LPS is an important virulence factor of A. pleuropneumoniae.

PMID- 9236295
TI  - Transposon-induced catalase-deficient Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens MKR, a nonpathogenic strain, has three catalase
      isozymes and one superoxide dismutase but no detectable peroxidase activity. A
      large number (8400) of transconjugants were obtained with pSUP1011::Tn5 suicide
      vector. The transposition frequencies were found to be greater in biparental
      mating than in triparental mating with helper plasmid. Mutants MLA31, MLA32,
      MLA41, and MLA41(a), generated by transposon mutagenesis, all lacked one of the
      catalase isozymes. Mutants were more susceptible to cell death than the wild type
      upon direct exposure to 10.0 mmol L-1 H2O2. The specific activity of the enzyme
      catalase was found to be higher in nitrogen-rich growth medium than carbon-rich
      growth medium.

PMID- 9236296
TI  - Oscillatoria anguistissima: a promising Cu2+ biosorbent.
AB  - Oscillatoria anguistissima rapidly adsorbs Cu2+ from aqueous solution. The
      adsorption of Cu2+ followed Freundlich Isotherm, and the amount of Cu2+ removed
      from solution increased with increasing Cu2+ concentration. The adsorption is pH
      dependent, and maximum Cu2+ removal occurs at pH 5. Of the various pretreatments,
      HCl treatment of the biomass increased the capacity for Cu2+ removal. Presence of
      Mg2+ and Ca2+ resulted in decline in the Cu2+ adsorption capacity of Oscillatoria
      cells. This species could also effectively remove Cu2+ from mine water containing
      68.4 microg/ml of Cu2+ at pH 3.45.

PMID- 9236299
TI  - Transformation of chlororesorcinol by the hydrocarbonoclastic yeasts Candida
      maltosa, Candida tropicalis, and Trichosporon oivide.
AB  - The inhibitory effects of chlorinated monoaromatic compounds on three
      hydrocarbonoclastic yeasts grown on glucose or resorcinol were examined. At
      concentrations of 1.0 M, all of the monoaromatic compounds were inhibitory. When
      the concentration of chlororesorcinol was significantly reduced (0.0005 M), the
      inhibition to each yeast was minimized. Extracts of the cultures of yeasts
      growing on resorcinol plus chlororesorcinol were analyzed for residual resorcinol
      and chlororesorcinol with high pressure liquid chromatography. Neither compound
      was detected in the culture broth of Candida maltosa, but several unidentified
      compounds were present. Only chlororesorcinol was detected in the culture broth
      of Trichosporon oivide, and both resorcinol and chlororesorcinol were present in
      extract from cultures of C. tropicalis. Cultures of C. maltosa grown on
      resorcinol-yeast nitrogen base, washed and suspended in phosphate buffer and
      subsequently incubated with chlororesorcinol, turned the culture broth a distinct
      pink color. The data indicate that C. maltosa has the potential to co-metabolize
      chlororesorcinol.

PMID- 9236300
TI  - Biofouling of groundwater systems by Thiothrix spp.
AB  - Thiothrix spp., sulfide-oxidizing filamentous bacteria, were found to be a
      principal bacterial component of aquatic biofilms causing biofouling in selected
      municipal water storage tanks, private wells, and drip irrigation systems in
      Florida. Treatments of up to 200 ppm chlorine in the affected systems could not
      prevent return of the biofouling problem. The water originated from the upper
      Floridan aquifer and associated surficial aquifers in central and north Florida.
      Samples were examined where visible biofilms had a white, filamentous appearance,
      indicative of Thiothrix spp. The detection of Thiothrix spp. was confirmed by
      enzyme-liked immunosorbent assay (ELISA), indirect immunofluorescence (IIF), and
      microbiological procedures. It was estimated through immunocytochemical
      procedures that Thiothrix spp. comprised 18% of the biofilm in the municipal
      water storage tanks. These observations confirm that specific biological and
      chemical interactions may induce physical changes leading to significant
      biofouling.

PMID- 9236301
TI  - Glucose and galactose transport in Bifidobacterium bifidum DSM 20082.
AB  - Sugar uptake was measured with 3H-galactose and 14C-glucose. Galactose transport
      system was not modified by inhibitors of known translocases and did not present a
      saturation kinetic with high concentration of galactose. Glucose incorporation
      was inhibited by lasalocid (cation symport inhibitor) and increased by KCl. The
      kinetic parameters KM and Vmax were respectively 9.16 mM and 26.56 nmol/min/mg
      cell protein. On the basis of this study, galactose crossed through the membrane
      by diffusion, and glucose was incorporated by a cation symport which is regulated
      by K+ ions.

PMID- 9236302
TI  - STP2201, a chromosomal promoter sequence of Streptococcus thermophilus.
AB  - Analysis of the structural and functional properties of chromosomal DNA fragments
      of Streptococcus thermophilus ST128 delineated the promoter sequence STP2201 and
      identified its -35, -10 and Shine-Dalgarno regions. STP2201 was used in cloning
      vectors derived from small resident plasmids pER8 (2094 bp) and pER371 (2672 bp)
      of S. thermophilus strains to facilitate expression of a Streptomyces sp. marker
      gene (cholesterol oxidase) in lactic acid bacteria. Cell extracts of ST128
      transformants converted up to 75% of cholesterol into 4-cholesten-3-one during 8
      h of incubation.

PMID- 9236303
TI  - Use of random amplification of polymorphic DNA (RAPD) and PCR-fingerprinting for
      genotyping a Scedosporium prolificans (inflatum) outbreak in four leukemic
      patients.
AB  - Four isolates of the pathogenic fungus Scedosporium prolificans (inflatum),
      causing a previously reported nosocomial outbreak in four leukemic patients, were
      typed by random amplification of polymorphic DNA (RAPD) with two different 10-mer
      primers and PCR-fingerprinting with the core sequence of phage M13 as a single
      primer. Both techniques allowed 10 additional clinical isolates of Scedosporium
      prolificans from different areas of Spain, including Scedosporium prolificans
      NCPF 2884, to be classified into 10 different molecular types. The four outbreak
      isolates consisted of three molecular types with two patients sharing a similar
      strain, and the remaining two patients infected by two different strains.

PMID- 9236304
TI  - Bioremediation of crude oil contamination with Acinetobacter sp. A3.
AB  - Acinetobacter sp. A3 is able to extensively degrade Bombay High Crude Oil (BHCO)
      and utilize it as the sole source of carbon. A total degradation of 70% BHCO was
      noted by the end of 120 h of growth of Acinetobacter sp. A3 under shake flask
      condition, 60% of which was due to biodegradation. In crude oil-contaminated soil
      (5%) amended with Acinetobacter sp. A3, there was both an increase in colony
      forming units (CFU) and crude oil degradation. This is in contrast to a decrease
      in CFU of the indigenous microorganisms and lower degradation in unamended soil
      within the same 30-day period. Also, Acinetobacter sp. A3-treated soil permitted
      better germination of Mung beans (Phaseolus aureus) and growth as evidenced by
      better length and weight of the plants and chlorophyll content of its leaves,
      which was attributed to the reduction in phytotoxicity of the crude oil owing to
      its degradation. This crude oil degradative capability of Acinetobacter sp. A3
      could be exploited for bioremediation purposes.

PMID- 9236305
TI  - The ethical and medical consequences of violence against women.

PMID- 9236306
TI  - Contraceptive use during lactational amenorrhea.
AB  - OBJECTIVE: The study uses data from nationally representative sample surveys in
      developing countries to estimate the overlap between lactational amenorrhea and
      contraceptive use during the first 6 months postpartum. METHOD: Secondary
      analyses of survey data were used to tabulate the proportion of the population in
      lactational amenorrhea among contraceptive users for all women, for postpartum
      women and for the country as a whole. RESULTS: Among postpartum women, the
      proportion in lactational amenorrhea was particularly high in Africa and the Near
      East and lower in Latin America and the Caribbean where breast-feeding practices
      have declined. The median duration of use for oral contraceptives is also
      presented as an aid to interpreting the significance of the findings.
      CONCLUSIONS: The significance of the findings is considered in the context of
      planning reproductive health services in the postpartum period. Decisions about
      timing of contraceptive use for postpartum women, while arrived at on an
      individual basis, also result from program strategies that focus counseling
      immediately postpartum or at a later interval, such as when menses resume. On a
      national level the impact of postpartum contraception policies on use of
      commodities may be substantial.

PMID- 9236307
TI  - Cesarean and postpartum hysterectomy.
AB  - OBJECTIVE: To review the cases of cesarean and postpartum hysterectomy. METHOD: A
      retrospective study of all cases of cesarean and postpartum hysterectomy during
      1985-1994. Maternal characteristics, method of delivery, indications for
      hysterectomy and complications were reviewed. RESULTS: The rate of cesarean and
      postpartum hysterectomy was 1:1667 deliveries. Half of these cases were delivered
      by cesarean section. The main indications for hysterectomy were massive bleeding
      due to uterine atony, abnormal placental adhesions or uterine rupture. Maternal
      morbidity was high and there was one maternal death. CONCLUSION: Cesarean and
      postpartum hysterectomy is a necessary life-saving operation. Although maternal
      mortality is rare, morbidity remains high. Prevention of complications that give
      rise to hysterectomy and optimally timed surgery should decrease maternal
      morbidity and mortality.

PMID- 9236308
TI  - Stillbirths and intrauterine infection, histologic chorioamnionitis and
      microbiological findings.
AB  - OBJECTIVE: To analyze whether placental inflammation is associated with
      stillbirth in Zimbabwe. METHOD: Placentas from 66 stillbirths (> 22 weeks'
      gestation; patients with congenital malformations, diabetes or preeclampsia were
      excluded) and 66 term live births were studied for the presence and severity of
      chorioamnionitis. The morphological results were compared with earlier presented
      microbiological findings in the same material. RESULTS: Chorioamnionitis was
      present in 79% of stillbirths and 30% of live births (O.R. 8.5, 95% C.I. 4.0-18).
      Nine percent of stillbirths but no live births presented vasculitis of the
      chorionic plate, which verified an inflammatory response from the infant (O.R.
      14, 95% C.I. 2.8-72). The same types of microorganisms were isolated from
      stillbirths and liveborns, but Escherichia coli and group B streptococci were
      more frequent among stillbirths. CONCLUSIONS: Morphological chorioamnionitis
      occurred 2.6 times more often in women with stillbirths than in women with live
      births. In 9% of stillbirths the infant showed an inflammatory response. Thus the
      infant was alive when the infection occurred and it is therefore reasonable to
      assume that infection was the cause of death.

PMID- 9236310
TI  - Prolongation of pregnancy in multiple pregnancy.
AB  - OBJECTIVE: The purpose of the study was to determine whether the use of
      prophylactic oral ritodrine or hospitalization for bed rest can prolong pregnancy
      in multiple pregnancy. METHODS: The study was conducted over a period of 8 years
      and included 189 cases of multiple pregnancy, all of which were delivered at the
      King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, between July 1986
      and August 1994. The patients were divided into three groups: the first group
      included 64 patients who received oral ritodrine from the 25th to the end of the
      37th week of gestation; the second group included 57 patients who were
      hospitalized from the 28th to the 32nd week of gestation; and the third group,
      considered the control group, included 68 patients who were managed on an
      outpatient basis only. Forty-six cases of multiple pregnancy were excluded from
      the study for a variety of reasons. RESULTS: The study showed an increase in
      gestational age at delivery, an increase in mean birth weight and a reduction in
      preterm delivery in the group treated with prophylactic ritodrine (P = 0.03). In
      the hospitalized group there was no effect on duration of gestation or reduction
      in preterm delivery, but there was an increase in mean birth weight (P = 0.04).
      Several patients experienced troublesome side effects with ritodrine. CONCLUSION:
      Our study indicates that the prophylactic use of beta-sympathomimetics is more
      effective, beneficial and less expensive than hospitalization for bed rest in
      prevention of preterm labor and delivery in multiple pregnancy.

PMID- 9236309
TI  - Pregnancy and cervical infection with human papillomaviruses.
AB  - OBJECTIVE: This investigation was undertaken to assess whether pregnancy
      represents a risk factor for human papillomavirus (HPV) infection which is
      independent of age and other known HPV risk factors. METHODS: One hundred eighty
      nine women were enrolled from the outpatient clinics of a large municipal
      hospital. The subjects completed a self-administered questionnaire and underwent
      a gynecological examination which included a cervicovaginal lavage. Lavage
      samples were assessed for the presence of HPV DNA by restriction enzyme analysis
      and Southern blot hybridization. Statistical significance was assessed by the chi
      2-test. Logistic regression was used to assess the association between pregnancy
      and HPV while controlling for the effect of other risk factors. RESULTS: The
      prevalence odds ratio (POR) for the association of pregnancy and HPV infection
      was 2.2 (95% C.I. 1.1-4.5). The prevalence of HPV increased with increasing
      gestational age (HPV prevalence of 18.9% among non-pregnant women vs. 27.3% in
      those in the first 12 weeks of pregnancy and 39.7% in those who were past the
      12th week of pregnancy). Although statistical significance was not achieved in a
      multivariate model which controlled for age, race/ethnicity, education, age at
      first coitus, number of sexual partners within the last year and parity, the POR
      associated with the current pregnancy (POR = 2.1) was not substantially changed
      by correcting for these risk factors, suggesting that these factors were not
      significant confounders of the association between pregnancy and HPV infection.
      CONCLUSION: Current pregnancy is associated with a modestly increased prevalence
      of cervical HPV infection. This association appears to be independent of age and
      other major HPV risk factors.

PMID- 9236311
TI  - Maternal mortality in a Kenyan pastoralist population.
AB  - OBJECTIVE: To measure maternal mortality among the Gabbra, a group of nomadic
      pastoralists living in a remote area of Kenya. METHOD: As part of a survey of 851
      households, information on the number of sisters of respondents who died of
      pregnancy-related causes was collected and the data were used to calculate
      maternal mortality statistics using the sisterhood (an indirect) method. RESULTS:
      The maternal mortality ratio for this population was 599 deaths per 100,000
      births (95% C.I. 424-775). The lifetime risk of dying around childbirth is 1 in
      30, and the proportion of ever-married sisters that died under 50 years of age
      who died from maternal causes is 0.48 (95% C.I. 0.38-0.58). CONCLUSION: The risk
      of dying of maternal causes is high in this population.

PMID- 9236313
TI  - Transcervical flexible endoscopy for first trimester embryonic/fetal evaluation.
AB  - OBJECTIVE: The aim of the study was to investigate the efficacy of flexible
      embryofetoscopy for visualization of the first trimester human embryo and fetus.
      METHOD: Twelve pregnant women scheduled for legal termination of pregnancy at 6
      12 weeks' gestation were included in the study. A flexible fiber optic endoscope
      with an eyepiece connected to a monitor was used. The sterile endoscope was
      passed transcervically under ultrasound guidance through the chorion into the
      chorionic cavity. Embryos/fetuses were observed directly through the intact
      amniotic membrane. RESULT: Successful embryofetoscopies with clear visualization
      of the embryo or fetus were accomplished in 50% of cases. There were no procedure
      related complications. CONCLUSION: Preliminary experience employing transcervical
      flexible embryofetoscopy for direct visualization of the first trimester human
      embryo and fetus suggest that this technique may be used for the early
      identification of congenital anomalies suspected by ultrasound and is expected to
      offer opportunities for embryo/fetal tissue sampling as well as for gene and cell
      therapies.

PMID- 9236312
TI  - Growth patterns of the humeral and femur length in a multiethnic population.
AB  - OBJECTIVES: To study whether there are any differences in growth of the femoral
      and humeral length between the three major ethnic groups in Malaysia viz Malays,
      Chinese and Indians. The effect on fetal growth by gender of the baby and parity
      of the mother was also studied. METHODS: The setting was the University of Kuala
      Lumpur. Thirty-four Malay, 35 Chinese and 34 Indian normal pregnant middle-class
      women were studied longitudinally by monthly ultrasound scans for 18 to 38 weeks
      of gestation. The data were subjected to regression analysis; the quadratic curve
      was found to be the most adequate. Dummy variables were used to determine any
      effects by gender, parity as well as ethnicity on the length of limb growth.
      There was no difference in birth weights of the three ethnic groups studied, nor
      in gender or parity. RESULTS: There were found to be significant differences in
      limb lengths of the Indians (longer) when compared with the Malays and Chinese.
      Parity seems to affect only Indians in whom the multiparous fetuses have shorter
      limb lengths than the primaparous. There appears to be no effect by gender.
      CONCLUSION: There appear to be definite differences in growth of limb length
      between the different Malaysian ethnic groups and this should be taken into
      account when growth charts are used and when fetal weight formulas are calculated
      using limb lengths. The limitation of this study was that the numbers of subjects
      studied were small. Larger studies will be able to confirm or refute the
      findings.

PMID- 9236314
TI  - Transvaginal sonography and hysteroscopy in women with postmenopausal bleeding.
AB  - OBJECTIVE: To make a prospective comparison between endometrial thickness
      determined by transvaginal sonography (TVS) and hysteroscopic findings in women
      with postmenopausal bleeding with histologic findings obtained by dilatation and
      curettage (D&C). METHODS: Eighty-one patients who had not received hormonal
      replacement therapy were scanned by transvaginal probe, and double-layer
      endometrial thickness was measured 1 day before hysterectomy and D&C. RESULTS:
      The histologic diagnosis was atrophy in 12 cases, irregular proliferative changes
      in 21, endometrial polyps in 16 hyperplasia in 16 and endometrial carcinoma in
      16. TVS detected 46 of 48 pathologic conditions, including all cases of
      endometrial carcinoma if the endometrial thickness (both layers) was > or = 5 mm
      (sensitivity 95.8%, specificity 4.5%). Hysteroscopy also detected the endometrial
      pathology in 46 of 48 cases but with a higher specificity (sensitivity 95.3%,
      specificity 93.9%). CONCLUSION: TVS and hysteroscopy are complementary diagnostic
      methods and could be accurately used to discriminate normal and pathologic
      conditions in patients with postmenopausal bleeding.

PMID- 9236315
TI  - Contrast sonography for inconclusive findings on routine sonography.
AB  - OBJECTIVES: We conducted a pilot study in 20 women with sonographically suspect
      endometria, to assess the value of contrast sonography and patient acceptance of
      this procedure. METHODS: Saline solution 4-20 ml was injected into the uterine
      cavity using an embryo transfer catheter, followed by hysteroscopy in 19 cases
      and hysterectomy in one case. RESULTS: A polyp was diagnosed in 12 patients, a
      submucous myoma in one patient, a proliferated endometrium in five patients and a
      placental polyp in one patient. A sonographic irregular structure was diagnosed
      in one patient which turned out to be coagula on hysteroscopy and histology. The
      procedure was well accepted by all patients. The diagnosis found by contrast
      sonography agreed in all cases with that found by hysteroscopy. CONCLUSION: Our
      results show that contrast sonography is an easy, quick and inexpensive procedure
      which increases the diagnostic value of vaginal sonography. The indications for
      contrast sonography are based on inconclusive sonographic findings, especially if
      polyps or submucous myoma are suspected.

PMID- 9236317
TI  - The effect of HLA on birth weight and placental weight in preeclampsia.

PMID- 9236316
TI  - Obstetric destructive procedures.

PMID- 9236318
TI  - Spontaneous bacterial endocarditis and aortic valve replacement complicating
      pregnancy.

PMID- 9236319
TI  - Ruptured uterus in Ethiopia.

PMID- 9236320
TI  - The use of low-dose aspirin to prevent preeclampsia.

PMID- 9236322
TI  - Vaginal evisceration: surgical repair with synthetic mesh.

PMID- 9236323
TI  - Removal of an intrauterine foreign body retained for 12 years.

PMID- 9236321
TI  - Doppler sonographic criteria for viability in ectopic pregnancy in correlation
      with histology.

PMID- 9236324
TI  - ACOG technical bulletin. Pulmonary disease in pregnancy. Number 224--June 1996.
      American College of Obstetricians and Gynecologists.
AB  - As pulmonary disorders become more prevalent overall, obstetricians will see an
      increasing number of these conditions in their pregnant patients. Management of
      respiratory disorders during pregnancy is not markedly different from management
      in the nonpregnant state, but the physician must be aware of the respiratory
      changes in pregnancy and how these affect the fetus in order to optimize
      treatment.

PMID- 9236325
TI  - ACOG committee opinion. Prevention of early-onset group B streptococcal disease
      in newborns. Number 173--June 1996. Committee on Obstetric Practice. American
      College of Obstetrics and Gynecologists.

PMID- 9236326
TI  - Didn't they do well?

PMID- 9236327
TI  - Predictors of CABG within one year of successful PTCA: a retrospective, case
      control study.
AB  - BACKGROUND: We previously have established characteristics predictive of the need
      for coronary artery bypass grafting (CABG) over many years after successful
      percutaneous transluminal coronary angioplasty (PTCA). In this study, we examined
      the factors associated with the need for CABG within 1 year of successful PTCA,
      and the recent impact of newer, catheter-based technologies. METHODS: From
      January 1982 through December 1995, 234 patients underwent CABG within 1 year of
      a successful "index" PTCA at our hospital. Emergency operations within 12 hours
      of index PTCA were excluded. These cases were matched with 234 controls who
      underwent a successful index PTCA but did not require a subsequent CABG during
      the next year. Cases were matched by the date of their index PTCA, and 1-year
      follow-up was complete for all patients. RESULTS: Before index PTCA there were no
      differences between the groups in terms of age, sex, diabetes, prior myocardial
      infarction, ejection fraction, duration of anginal symptoms, hypertension,
      hyperlipidemia, family history, or obesity (all nonsignificant). At index PTCA
      the cases had a greater mean number of lesions measuring 70% or greater compared
      with the controls (2.8 versus 1.8, respectively; p < 0.0001). The cases were more
      likely to have critical (70% or greater) proximal left anterior descending
      artery, proximal first obtuse marginal artery, and right posterior descending
      artery stenoses. The use of stents or atherectomy devices was not significantly
      more common among the controls (21% of controls versus 17.1% of cases; p = 0.35).
      Complete revascularization was achieved in significantly fewer of the cases than
      the controls (91 versus 156, respectively; p < 0.0001). The cases underwent CABG
      at a mean of 3 months (86% within 6 months) after PTCA. Among those who had a
      diagnostic catheterization, 52% of the patients had both restenosis of a dilated
      lesion and progression of other disease. Only 5 of 75 patients who had restenosis
      of a dilated lesion had a stent or an atherectomy device used at index PTCA. Of
      note, 13% (30 of 234) required an emergency operation, with an overall operative
      mortality rate of 3% (7 of 234). CONCLUSIONS: Although the likelihood of local
      restenosis is decreased by newer interventional techniques, the need for CABG
      within 1 year after successful PTCA is not diminished. The number of critical
      lesions and their location are the best predictors of the need for early CABG. If
      early post-PTCA CABG is to be avoided, patients who cannot be completely
      revascularized by PTCA should be revascularized by CABG.

PMID- 9236328
TI  - Improved survival with multiple left-sided bilateral internal thoracic artery
      grafts.
AB  - BACKGROUND: Although conceptually sound, the use of multiple internal thoracic
      artery (ITA) bypass grafts to improve long-term clinical results remains
      controversial. This operation typically involves grafting the left ITA to the
      anterior descending artery and the right ITA to the right coronary artery. Past
      clinical studies of bilateral ITA operations have not examined comparative
      results associated with which coronary arteries received the ITA bypass grafts.
      Because grafting a superior conduit to an artery of lesser physiologic importance
      might reduce the clinical benefits, we compared the outcomes of patients
      receiving different configurations of bilateral ITA operations. METHODS: The
      study group was 498 consecutive bilateral ITA operations, constituting the 10
      year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3
      years), and was 94.2% complete. These patients were divided into two groups, 311
      patients (group I) who underwent the traditional operation (left ITA to the left
      anterior descending artery, right ITA to the right coronary artery), and 187
      patients (group II) who received revascularization of branches of the left
      coronary artery (left ITA to the circumflex system and right ITA to the left
      anterior descending artery). RESULTS: The study groups were similar in age,
      severity of disease, number of bypassed arteries, ejection fraction, diabetes,
      hypertension, and duration of operation. There were more male patients in group
      II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA
      bypass grafts influenced survival independent of gender (p = 0.0288). Operative
      morbidity and mortality were similar between groups. Ninety-three patients had
      repeat angiography with equivalent patency rates of the ITA conduits (91.7%
      versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate
      demonstrated a significant improvement in survival of patients in group II who
      received both ITA bypass grafts to left-sided arteries (p = 0.021), with the
      survival curves diverging at 6 years. More patients in group II were in New York
      Heart Association class I or II, but the difference was not statistically
      significant (94.6% versus 91.6%). Only 2 patients required reoperation.
      CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA
      operations is achieved by grafting the ITA conduits to coronary arteries that
      supply more left ventricular muscle.

PMID- 9236329
TI  - Is an integrated approach warranted for concomitant carotid and coronary artery
      disease?
AB  - BACKGROUND: The management of patients with severe, concomitant coronary and
      carotid artery occlusive disease is controversial. METHODS: Between 1975 and
      1996, 512 patients (mean age, 64.9 years; 70% male) were admitted for coronary
      revascularization; 316 (61.7%) had asymptomatic, severe carotid disease (stenosis
      > 70%) and 196 (38.3%) had symptomatic carotid disease (159 [31.1%] with
      transient ischemia and 37 [7.2%] with completed stroke). In group 1, coronary
      revascularization and carotid endarterectomy were simultaneously performed in 255
      patients (49.8%) with unstable angina. In group 2 (staged approach), carotid
      endarterectomy was performed before coronary revascularization in 257 patients
      (50.2%) without unstable angina. RESULTS: Before 1986, the incidence of stroke
      and death was greater in group 1 (n = 149) than in group 2 (n = 156) (14 [9.4%]
      versus 4 [2.6%]; p < 0.01). Since 1986, outcomes in group 1 (n = 106) and group 2
      (n = 101) have been similar for stroke (2 [1.9%] versus 2 [2.0%]), death (4
      [3.8%] versus 3 [3.0%]), and myocardial infarction (4 [3.8%] versus 5 [5.0%]).
      Significant univariate and multivariate predictors of adverse outcome were
      primarily heart-related (reoperation, intraaortic balloon use, ejection fraction
      < 0.50, and angina grade 4 for death; age > 70 years and congestive heart failure
      for stroke). CONCLUSIONS: Despite highly selected populations, contemporary
      surgical results do not indicate that staged treatment of severe, concomitant
      coronary and carotid artery occlusive disease has an advantage over simultaneous
      treatment. Advances in myocardial protection and perioperative hemodynamic
      management may account for the low incidences of stroke and death in these
      operations.

PMID- 9236330
TI  - Is vertical vein ligation necessary in repair of total anomalous pulmonary venous
      connection?
AB  - BACKGROUND: In the repair of total anomalous venous connection, vertical vein
      ligation is recommended to eliminate left-to-right shunting. However, the small
      left heart chambers may not always tolerate the immediate increase in blood flow
      after combined repair and vein ligation. METHODS: A retrospective review of 23
      infants and children undergoing correction of total anomalous pulmonary venous
      connection was undertaken to determine whether vertical vein ligation is a
      necessary component of successful surgical repair. In 14 patients this vein was
      ligated, whereas in 9 it was left patent. Six patients who underwent ligation and
      5 who did not had pulmonary venous obstruction before operation. RESULTS: The
      operative mortality rate was 36% (5 of 14 patients) for the ligated group
      compared with 0% (0 of 9 patients) for the nonligated group (p = 0.06). All
      deaths occurred in patients with preoperative obstruction and a low mean left
      atrial pressure, and four of the deaths were directly attributable to left heart
      failure. Follow-up echocardiography in patients in whom the vertical vein was not
      ligated revealed adequate cardiac function and no residual left-to-right flow
      through the previously patent venous conduit. CONCLUSION: Vertical vein ligation
      during the repair of total anomalous pulmonary venous connection is not routinely
      necessary and actually may be undesirable in patients with preoperative
      obstruction, in whom the left heart chambers are particularly small.

PMID- 9236331
TI  - Anticoagulation in children with mechanical valve prostheses.
AB  - BACKGROUND: Clotting complications in patients with mechanical valve prostheses
      can be prevented with either warfarin sodium (Coumadin; DuPont, Wilmington, DE)
      or antiplatelet agents. In children, it is not known whether one treatment
      regimen is more effective or safe than the other. METHODS: We prospectively
      followed up 64 children and young adults (aged 18 years or younger at
      implantation) with a mechanical valve on the left side of the heart, from October
      1986 through October 1996. Forty-eight patients were treated with Coumadin and 16
      with aspirin and dipyridamole. The two groups were similar in age, sex, valve
      location and size, mean length of follow-up, and operative indication. There has
      been a total follow-up of 272 patient-years on Coumadin and 116 patient-years on
      aspirin and dipyridamole. RESULTS: There was no difference between the two groups
      in survival or freedom from thromboembolism. Bleeding occurred more often in the
      patients taking Coumadin, but this difference was not statistically significant.
      Analysis of the literature showed thromboembolism and bleeding rates to be
      similar in the patients receiving Coumadin and those receiving antiplatelet
      agents. CONCLUSIONS: Coumadin and the combination of aspirin plus dipyridamole
      provided similar protection against complications in this group of children and
      young adults with left-sided St. Jude (St. Paul, MN) mechanical valves. The
      choice between the two regimens may depend on other factors, such as patient
      preference and convenience.

PMID- 9236332
TI  - Modified ultrafiltration reduces postoperative morbidity after cavopulmonary
      connection.
AB  - BACKGROUND: Modified ultrafiltration reduces the deleterious effects of
      cardiopulmonary bypass in children. Patients undergoing repair of single
      ventricle cardiac anomalies may be particularly sensitive to these adverse
      effects, and benefit from the use of modified ultrafiltration. METHODS: From
      January 1995 to June 1996, 120 consecutive cavopulmonary operations were
      performed at The Children's Hospital of Philadelphia. Procedures included lateral
      tunnel fenestrated Fontan (n = 50), extracardiac Fontan (n = 5), hemi-Fontan (n =
      60), and bidirectional Glenn shunt (n = 5). Modified ultrafiltration was
      performed after cardiopulmonary bypass in 41 patients, and results were compared
      by t test with a control group of 79 patients in whom modified ultrafiltration
      was not used. RESULTS: There was one death for an operative (30-day) mortality of
      0.8%. Age, weight, diagnosis, ischemic arrest time, and cardiopulmonary bypass
      time were similar between the modified ultrafiltration and control groups.
      Postoperative blood use, chest tube output, the incidence of pleural and
      pericardial effusions, and hospital stay were all significantly decreased when
      modified ultrafiltration was used. CONCLUSIONS: By lowering the perioperative
      morbidity of staged cavopulmonary operations, modified ultrafiltration makes an
      important contribution to improving outcome after the correction of single
      ventricle cardiac anomalies.

PMID- 9236333
TI  - Risk factors for higher cost in congenital heart operations.
AB  - BACKGROUND: For many congenital heart defects, hospital mortality is no longer a
      sensitive parameter by which to measure outcome. Although hospital survival rates
      are now excellent for a wide variety of lesions, many patients require expensive
      and extensive hospital-based services during the perioperative period to enable
      their convalescence. These services can substantially increase the cost of care
      delivery. In today's managed care environment, it would be useful if risk factors
      for higher cost could be identified preoperatively so that appropriate resources
      could be made available for the care of these patients. The focus of this
      retrospective investigation is to determine if risk factors for high cost for
      repair of congenital heart defects can be identified. METHODS: We assessed
      financial risk by tracking actual hospital costs (not charges) for 144 patients
      undergoing repair of atrial septal defect (58 patients), ventricular septal
      defect (48 patients), atrioventricular canals (14 patients), or tetralogy of
      Fallot (24 patients) at Duke University Medical Center between July 1, 1992, and
      September 15, 1995. Furthermore, we were able to identify where the costs
      occurred within the hospital. Financial risk was defined as a large (> 60% of
      mean costs) standard deviation, which indicated unpredictability and variability
      in the treatment for a group of patients. RESULTS: Cost for atrial septal defect
      repair was predictably consistent (low standard deviation) and was related to
      hospital length of stay. There were factors, however, for ventricular septal
      defect, atrioventricular canal, and tetralogy of Fallot repair that are
      identifiable preoperatively that predict low- and high-risk groups using cost as
      an outcome parameter. Patients undergoing ventricular septal defect repair who
      were younger than 6 months of age at the time of repair, who required
      preoperative hospital stays of longer than 7 days before surgical repair, or who
      had Down's syndrome had a less predictable cost picture than patients undergoing
      ventricular septal defect repair who were older than 2 years, who had short (< 4
      days) preoperative hospitalization, or who did not have Down's syndrome ($48,252
      +/- $42,539 versus $15,819 +/- $7,219; p = 0.008). Patients with atrioventricular
      canals who had long preoperative hospitalization (> 7 days), usually due to
      pneumonia (respiratory syncytial virus) with preoperative mechanical ventilation
      had significantly higher cost than patients with atrioventricular canals who
      underwent elective repair with short preoperative hospitalization ($83,324 +/-
      $60,138 versus $26,904 +/- $5,384; p = 0.05). Patients with tetralogy of Fallot
      had higher costs if they had multiple congenital anomalies, previous palliation
      (combining costs of both surgical procedures and hospital stays), or severe "tet"
      spells at the time of presentation for operation compared with patients without
      these risk factors ($114,202 +/- $88,524 versus $22,241 +/- $7,071; p = 0.0005).
      One patient (with tetralogy of Fallot) with multiple congenital anomalies died 42
      days after tetralogy of Fallot repair of sepsis after a gastrointestinal
      operation. Otherwise, hospital mortality was 0% for all groups. CONCLUSIONS: Low
      mortality and good long-term outcome for surgical correction of congenital heart
      defects is now commonplace, but can be expensive as some patients with complex
      problems receive the care necessary to survive. This study demonstrates that it
      is possible to identify factors preoperatively that predict financial risk. This
      knowledge may facilitate implementation of risk adjustments for managed care
      contracting and for strategic resource allocation.

PMID- 9236334
TI  - Refinement of the alpha aminooleic acid bioprosthetic valve anticalcification
      technique.
AB  - BACKGROUND: Aminooleic acid treatment has been demonstrated to prevent porcine
      valve calcification and to protect valvular hemodynamic function. Initial
      enthusiasm was tempered by histologic studies of these AOA valves, which showed
      cuspal hematomas, structural loosening, and surface roughening. This prompted a
      systematic review of the AOA treatment process. Unsolubilized particles of alpha
      aminooleic acid present in the treatment solution were identified as the cause of
      mechanical abrasion of valve cusps during processing. These particles were
      eliminated with a revamped protocol, which included filtration of the AOA
      solution before valve preparation. METHODS: Porcine aortic valve cusps treated
      with this modified AOA protocol (AOA II) were studied in a rat subdermal implant
      model of mineralization. A juvenile sheep trial was then used to confirm the
      antimineralization effects of AOA II on glutaraldehyde-fixed porcine aortic roots
      in a circulatory model of accelerated calcification. RESULTS: Retrieved AOA II
      treated cusps from the subdermal model were markedly less calcified than control
      cusps (AOA II, 1 +/- 0, 17 +/- 4, 23 +/- 6, and 17 +/- 10 versus control, 189 +/-
      14, 251 +/- 16, 250 +/- 14, and 265 +/- 10 mg calcium/mg sample at 4, 8, 12, and
      16 weeks, respectively; p < 0.0001). Morphologic examination of the AOA II cusps
      of the valves retrieved from the sheep demonstrated freedom from the structural
      loosening, surface roughening, and hematoma formation that had limited the
      utility of the original AOA preparation technique. Cusps from AOA II-treated
      porcine roots had significantly less calcium than control cusps (AOA II, 5.5 +/-
      3.0 mg/g; control, 91.2 +/- 19.5 mg/g; p = 0.0004). The aortic walls had similar
      levels of calcification (AOA II, 156 +/- 73 mg/g; control, 159 +/- 10 mg/g; p =
      not significant). CONCLUSIONS: These data suggest that the modified AOA technique
      warrants further evaluation as an antimineralization treatment for glutaraldehyde
      fixed porcine bioprostheses.

PMID- 9236336
TI  - Development of a minimally invasive technique for coronary revascularization in a
      porcine model.
AB  - BACKGROUND: This porcine model was designed to develop a minimally invasive
      method for internal mammary artery (IMA) grafting using an anterior mediastinal
      approach and without routine use of cardiopulmonary bypass. METHODS: Assessment
      was made of IMA mobilization through a small parasternal incision, the
      feasibility of coronary artery grafting with cardiopulmonary bypass using this
      approach, and conditions for off-pump bypass grafting. RESULTS: In group 1, 6
      pigs underwent IMA mobilization through a 5-cm horizontal midparasternal
      incision. Of the 2 group 2 pigs, 1 underwent IMA grafting to the left anterior
      descending coronary artery and the other, bilateral IMA grafting to the left
      anterior descending and right coronary arteries using femoral-vessel
      cardiopulmonary bypass. In group 3, 4 of 10 pigs had successful off-pump grafting
      during retrograde regional coronary venous perfusion of arterial blood.
      Retrograde coronary venous perfusion could not be established in the other 6
      pigs, and attempts at off-pump grafting failed. CONCLUSIONS: The study
      demonstrates that coronary artery grafting with the IMA by this minimally
      invasive off-pump method is feasible, although it draws attention to areas of
      concern and potential methods of correction. The model provides a realistic and
      important learning platform for the surgical issues involved with this minimally
      invasive technique.

PMID- 9236335
TI  - Clinical assessment of prolonged myocardial preservation for patients with a
      severely dilated heart.
AB  - BACKGROUND: The purpose of this study was to compare the myocardial protective
      effect of histidine-tryptophan-potassium and glucose-insulin-potassium
      cardioplegic solutions in patients with a dilated heart (left ventricular
      diastolic diameter > 55 mm, left ventricular systolic diameter > 45 mm)
      associated with prolonged cross-clamp time (longer than 200 minutes). METHODS: We
      selected 20 patients with dilated hearts due to severe aortic regurgitation.
      Glucose-insulin-potassium cardioplegia was used in 11 patients and histidine
      tryptophan-potassium cardioplegia was used in 9 patients. RESULTS: After
      operation, the cardiac index was significantly increased in the histidine
      tryptophan-potassium group (p < 0.05). Postoperative percent fractional
      shortening was 13.4% +/- 3.1% in the glucose-insulin-potassium group and 23.6% +/
      2.6% in the histidine-tryptophan-potassium group (p < 0.05). Creatine kinase
      levels were significantly lower in the histidine-tryptophan-potassium group than
      that in the glucose-insulin-potassium group (p < 0.05). The incidence of
      ventricular arrhythmia (higher than Lown's grade 2) was lower in the histidine
      tryptophan-potassium group. CONCLUSIONS: These data support the superiority of
      the histidine-tryptophan-potassium method over the glucose-insulin-potassium
      method for protection of the dilated heart during prolonged ischemia in open
      heart operations.

PMID- 9236337
TI  - Influence of bicaval anastomoses on late occurrence of atrial arrhythmia after
      heart transplantation.
AB  - BACKGROUND: The standard technique for orthotopic heart transplantation includes
      right and left atrial anastomoses, which potentially disturb the integrity of the
      donor atria. Consequently, electrophysiologic abnormalities such as atrial
      flutter and fibrillation may occur even late after heart transplanation. METHODS:
      Over a 3-year period, 39 heart transplantations were performed using a standard
      right atrial anastomosis (group A), and 40 were done using bicaval anastomoses
      (group B). In each group, data of 30 consecutive patients with a minimum follow
      up of 9 months were reviewed retrospectively to assess the incidence of atrial
      arrhythmia after hospital discharge. RESULTS: Early postoperatively, there was no
      difference in the duration of temporary pacemaker requirement and incidence of
      permanent pacemaker implantation (group A, 7%; group B, 7%; not significant)
      between the two groups. In 12 patients in group A (40%), 16 episodes of atrial
      flutter and fibrillation were detected 20 to 205 days after heart
      transplantation. In group B, 1 patient (4%) suffered from atrial fibrillation on
      day 116 after the operation (p < 0.001). CONCLUSIONS: Preservation of the
      integrity of the right donor atrium by construction of bicaval anastomoses
      results in a significantly decreased incidence of atrial flutter and fibrillation
      after heart transplantation when compared with the standard technique.

PMID- 9236338
TI  - Zinc-bis-histidinate preserves cardiac function in a porcine model of
      cardioplegic arrest.
AB  - BACKGROUND: We examined the ability of zinc-bis-histidinate to preserve
      postarrest myocardial function when added to a standard crystalloid cardioplegic
      solution. METHODS: Domestic pigs (35 to 50 kg) on left-sided cardiopulmonary
      bypass were subjected to 90 minutes of regional ischemia followed by 60 minutes
      of hypothermic cardioplegic arrest induced by antegrade infusion of 20 mL/kg cold
      St. Thomas' #2 cardioplegic solution with or without 100 mumol/L of zinc-bis
      histidinate and maintained by infusion of 10 mL/kg of the same every 20 minutes.
      During reperfusion function was assessed at 1 and 3 hours over increasing
      preloads using the right-sided bypass method. RESULTS: At roller pump flows up to
      2,000 mL/min, stroke work index-end-diastolic pressure curves were significantly
      (p < 0.05) higher and shifted to the left in treated hearts. In a series of pigs,
      echocardiography was used to determine end-diastolic and end-systolic volumes. At
      roller pump flows up to 3,500 mL/min, end-systolic pressure-end-systolic volume
      curves were significantly higher and shifted to the left in treated hearts. Left
      ventricular ejection fraction, fractional shortening, stroke volume, and cardiac
      output were significantly (p < 0.05) higher in treated hearts. Electron
      microscopy revealed that mitochondria in tissue not at risk appeared more swollen
      in control hearts. CONCLUSIONS: The results of this study support the conclusion
      that zinc-bis-histidinate is effective as a myocardial preservative when added to
      a crystalloid cardioplegic solution.

PMID- 9236339
TI  - Cardiac binding in experimental heart failure.
AB  - BACKGROUND: Cardiomyoplasty is a potential therapy for heart failure. Its
      benefits are attributed to systolic augmentation (dynamic cardiomyoplasty) and
      prevention of cardiac dilatation (static cardiomyoplasty). To evaluate the static
      component, we used an artificial membrane for cardiac binding in a canine model
      of heart failure. METHODS: Intracoronary doxorubicin was administered weekly for
      4 weeks to induce heart failure in 10 dogs, each of which was assigned to one of
      two treatment groups: (1) no treatment, or (2) cardiac binding. Hemodynamic data
      were obtained at operation and at 7 weeks after operation. Echocardiography was
      performed weekly. RESULTS: Left ventricular end-diastolic pressure and diameter,
      and right ventricular end-diastolic diameter increased in group 1 (from 9.6 +/-
      6.1 to 19.6 +/- 2.3 mm Hg, p = 0.009; from 3.9 +/- 0.4 to 5 +/- 0.3 cm, p =
      0.0013; and from 1.6 +/- 0.2 to 1.9 +/- 0.3 cm, p = 0.0036, respectively).
      Ejection fraction fell in group 1 from 0.60 +/- 0.10 to 0.40 +/- 0.04 (p =
      0.0009) and in group 2 from 0.56 +/- 0.02 to 0.40 +/- 0.04 (p = 0.0001), but the
      difference between groups was not significant. CONCLUSION: Cardiac binding
      reduces the ventricular dilatation associated with heart failure without
      exacerbating left ventricular dysfunction.

PMID- 9236340
TI  - Intramural blood flow of skeletal muscle ventricles functioning as aortic
      counterpulsators.
AB  - BACKGROUND: Skeletal muscle ventricles (SMVs) working as aortic counterpulsators
      have provided long-term left ventricular assistance under experimental
      conditions. However, gradual deterioration of SMV pump function and rupture have
      been observed, and this may be related to compromised intramural blood flow
      during synchronized counterpulsation under systemic working conditions. METHODS:
      Transformed, double-layered SMVs in 6 sheep were stimulated for 3-minute periods
      (5 V, 30 Hz, burst duration and delay from QRS both 40% of the cardiac cycle) to
      work as diastolic counterpulsators in the systemic circulation at a 1:2
      (SMV:heart) and 1:1 ratio, and on a mock circulation with low-pressure loading
      conditions at a 1:2 ratio. Thoracodorsal artery blood flow was monitored by
      ultrasonic flow probe, and intramural blood flow distribution was investigated by
      fluorescent microspheres. Thoracodorsal venous lactate concentrations were
      measured before and after each period of stimulation. RESULTS: Thoracodorsal
      artery blood flow increased significantly (p < 0.001) after stimulation. The
      magnitude of augmentation (89%; 95% confidence interval, 36% to 163%) was similar
      for all working conditions studied. Reactive hyperemia was observed after most
      1:1 regimens but was rare after 1:2 regimens. A significant (p < 0.05) 15%
      increase in serum lactate levels was present after 1:1 regimens only. All
      regimens of stimulation resulted in a significant increase (p < 0.01) in blood
      flow to sections in the outer wall of the SMV, but a significant increase (p <
      0.05) in blood flow to sections in the inner wall was observed only under low
      loading conditions. CONCLUSIONS: Skeletal muscle ventricles subjected to 1:1
      systemic counterpulsation regimens work under partly anaerobic conditions. High
      loading conditions may compromise SMV inner wall blood flow.

PMID- 9236341
TI  - Effects of specific sodium/hydrogen exchange inhibitor during cardioplegic
      arrest.
AB  - BACKGROUND: The accumulation of intracellular sodium during myocardial ischemia
      couples an inappropriate calcium influx and depressed cardiac recovery during
      subsequent reperfusion. The effects of the selective sodium/ hydrogen exchange
      inhibitor HOE 694 are evaluated during myocardial ischemia and reperfusion.
      METHODS: Ten isolated rat hearts were subjected to a 2-minute infusion of St.
      Thomas' cardioplegia +/- 1 mumol/L HOE 694 followed by 50 minutes' normothermic
      (37 degrees C) global ischemia. Intracellular sodium accumulation was
      continuously measured using triple quantum filtered 23Na nuclear magnetic
      resonance spectroscopy without chemical shift reagents. Hemodynamic variables
      were assessed before and after ischemia. RESULTS: The addition of 1 mumol/L HOE
      694 to St. Thomas cardioplegic solution (n = 5) attenuated the accumulation of
      intracellular sodium after 50 minutes' ischemia (160.5% +/- 9.1% versus 203.4% +/
      10.9% [mean +/- standard error], HOE 694 versus control, respectively; p =
      0.014) and after the initial reperfusion period (first 30 minutes) (288.7% +/-
      10.2% versus 335.9% +/- 10.3%; p = 0.008). HOE 694-treated hearts showed
      significantly improved postischemic recovery of left ventricular developed
      pressure (53.5% +/- 8.4% versus 26.4% +/- 6.6%; p = 0.036) and rate-pressure
      product (40.2% +/- 6.9% versus 13.2% +/- 5%; p = 0.014). Postischemic recovery of
      coronary flow was not significantly different between the two groups (68.6% +/-
      5.9% versus 55.5% +/- 4.6%, HOE 694 versus control, respectively; p = 0.11).
      CONCLUSIONS: The addition of 1 mumol/L HOE 694 to cardioplegic solution
      attenuates the increase of intracellular sodium during myocardial ischemia and
      early reperfusion. This is coupled with an improved recovery of contractile
      function, possibly as a result of decreased sodium and calcium overload of
      ischemic myocardium.

PMID- 9236342
TI  - Cooling gradients and formation of gaseous microemboli with cardiopulmonary
      bypass: an echocardiographic study.
AB  - BACKGROUND: Previous studies demonstrated gas emboli formation during rewarming
      from hypothermia on cardiopulmonary bypass when the temperature gradient exceeded
      a critical threshold. It also has been suggested that formation of arterial gas
      emboli may occur during cooling on cardiopulmonary bypass when cooled oxygenated
      blood exiting the heat exchanger is warmed on mixture with the patient's blood.
      The purpose of this study was to determine under what circumstances gas emboli
      formation would occur during cooling on cardio-pulmonary bypass. METHODS: Eight
      anesthetized mongreal dogs were placed on cardiopulmonary bypass using a roller
      pump, membrane oxygenator, and arterial line filter. For emboli detection, we
      positioned a transesophageal echocardiographic probe at the aortic arch distal to
      the aortic cannula and Doppler probes at the common carotid artery and the
      arterial line. Cooling gradients between normothermic blood and cooled arterial
      perfusate of 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 0 degree C
      (isothermal controls) were investigated. In addition to preestablished
      temperature gradients, we investigated the effect of rapid cooling (maximal flow
      through the heat exchanger at a water bath temperature of 4 degrees C) after the
      initiation of normothermic cardiopulmonary bypass. RESULTS: Minimal gas emboli
      were detected at the aortic arch at gradients of 10 degrees C or greater. The
      incidence of emboli was related directly to the magnitude of the temperature
      gradient (p < 0.01). No emboli were detected at the carotid artery. During rapid
      cooling, no emboli were observed either at the aorta or at the carotid artery.
      CONCLUSIONS: Cooling gradients of 10 degrees C or greater may be associated with
      gas emboli formation, but they may be of limited clinical significance because no
      emboli were detected distal to the aortic arch. During the application of rapid
      cooling, no emboli formation was observed.

PMID- 9236343
TI  - Discrete membranous subaortic stenosis: improved results after resection and
      myectomy.
AB  - BACKGROUND: Despite an adequate resection, a significant recurrence rate is
      encountered in patients undergoing operation for discrete membranous subaortic
      stenosis. The fibrous membrane and hypertrophied myocardium commonly are removed,
      but because of the involved risks, the resection may be inadequate and contribute
      to the recurrence rate. METHODS: A review of the cases of 23 patients undergoing
      operation for discrete membranous subaortic stenosis from 1980 to 1994 was
      undertaken. Fourteen patients (61%) had coexisting cardiac lesions, all of which
      were concomitantly repaired. RESULTS: The left ventricle-aorta gradient decreased
      from a preoperative mean of 63.39 +/- 7.63 mm Hg to 15.17 +/- 3.06 mm Hg
      postoperatively (p < .001) during a mean follow-up of 3.32 +/- 0.58 years. Aortic
      insufficiency decreased postoperatively in 8 patients (34.8%), remained unchanged
      in 6 patients (26.1%), and showed only insignificant progression in 4 patients
      (17.4%). There were no early deaths, and the single late death was not cardiac
      related. No patient had development of endocarditis or heart block or required a
      pacemaker. One patient (4.3%) had a recurrence, which required reoperation.
      CONCLUSIONS: Our results suggest that aggressive myectomy in concert with
      membrane resection constitutes safe treatment for discrete membranous subaortic
      stenosis and is associated with low rates of endocarditis, recurrence, and
      progression of aortic insufficiency.

PMID- 9236344
TI  - A survey on minimally invasive coronary artery bypass grafting.
AB  - BACKGROUND: There is increasing interest in performing minimally invasive
      coronary artery bypass grafting. To evaluate the current level of acceptance and
      utility of this procedure a survey of 162 cardiothoracic surgeons was conducted.
      RESULTS: Currently only 16% of surveyed surgeons performed more than 10 minimally
      invasive coronary artery bypass grafting procedures. Most were less than 55 years
      old and in private practice. The majority predicted that it will be indicated in
      less than 25% of coronary artery bypass grafting cases and considered minimally
      invasive coronary artery bypass grafting a modification of existing techniques
      rather than investigational. Most believed exposure and stabilization of the
      coronary arteries on the beating heart to be the most challenging part and
      expressed concern with quality of the anastomosis. CONCLUSIONS: We conclude that
      minimally invasive coronary artery bypass grafting is rapidly gaining acceptance
      in younger surgeons as techniques are improved. Despite concerns with adequacy of
      anastomosis the procedure is not considered investigational and follow-up is not
      rigorous.

PMID- 9236346
TI  - Single access for minimally invasive aortic valve replacement.
AB  - BACKGROUND: The method of replacing the aortic valve via a minithoracotomy has
      been reported in the recent literature. Although this strategy has clear
      advantages, further refinements of the process make the procedure even less
      invasive. METHODS: Aortic valve replacement was performed in 27 patients via a
      right parasternal minithoracotomy without rib resection. Cardiopulmonary bypass
      was connected through the same access site. Standard surgical technique and
      equipment were employed. RESULTS: There were no intraoperative complications. All
      patients survived and could be discharged home within 1 week, except 1.
      Cardiopulmonary bypass time, aortic cross-clamp time, and total operating time
      averaged 114 +/- 26, 76 +/- 19, and 190 +/- 40 minutes, respectively. Three
      patients could be extubated in the operative theater, the others in the intensive
      care unit at an average of 10 +/- 7 hours postoperatively. Chest drainage lost
      averaged 430 +/- 380 mL. CONCLUSIONS: The advantages of this method include
      further reduction of surgical trauma, early mobilization, and rehabilitation of
      the patient. Surgical technical improvements include avoidance of groin
      cannulation, simpler equipment, safe venting of the left ventricle, and
      preservation of chest wall integrity.

PMID- 9236345
TI  - Surgical management of Behcet's aortitis: a report of eight patients.
AB  - BACKGROUND: Behcet's aortitis is one of the most severe manifestations of
      Behcet's disease. However, there have been few reports of this rare entity. This
      article we describe our experience with surgical treatment of Behcet's aortitis
      in 8 patients. METHODS: From May 1978 to February 1995, we operated on 8 patients
      with Behcet's aortitis. All patients were followed up for a total of 54.4 patient
      years (mean, 6.8 years). RESULTS: There were no operative deaths, but 1 patient
      died in the hospital of ventricular fibrillation. Another death occurred as a
      result of pseudoaneurysm rupture 10 months after operation. Fourteen operations
      were performed on eight patients: a second operation was performed on four
      patients, and a third operation was performed on two patients. The translocated
      Bentall procedure, a modified Bentall procedure, was performed six times. One
      patient required a second operation for graft detachment, but the others have
      done well without further surgical intervention. Aortic valve replacement was
      performed six times, and three reoperations were needed after aortic valve
      replacement. CONCLUSIONS: The translocated Bentall procedure may be effective for
      Behcet's aortitis, but further investigation is necessary.

PMID- 9236347
TI  - Effect of cardiopulmonary bypass under tepid temperature on inflammatory
      reactions.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) causes inflammatory reactions and
      abnormal responses of vascular resistance. Theoretically, the difference in the
      blood temperature during CPB may influence the degree of CPB-induced inflammatory
      reactions. METHODS: To elucidate the effect of the perfusate temperature during
      CPB, serum levels of inflammatory cytokines, neutrophil elastase, complements,
      and vasoactive substances were measured in 18 patients undergoing elective
      coronary artery bypass grafting under tepid temperature (34 degrees C) and
      moderate hypothermia (28 degrees C). Respiratory index and systemic vascular
      resistance index during and after CPB and intubation time after postoperative
      course were also analyzed. RESULTS: The patterns of the change in interleukin-8
      and neutrophil elastase were significantly different between the two groups. The
      tepid group showed an earlier decrease in interleukin-8 and neutrophil elastase
      levels as compared with the hypothermic group. The prostaglandin E2 level just
      after CPB was significantly higher in the tepid group than in the hypothermic
      group. Systemic vascular resistance index and respiratory index and intubation
      time were significantly lower in the tepid group than in the hypothermic group.
      CONCLUSIONS: These results demonstrated that tepid CPB affected the inflammatory
      cytokine release and neutrophil activation compared with hypothermic CPB,
      resulting in the attenuation of respiratory dysfunction. This may suggest a
      beneficial effect of tepid temperature in CPB with possible attenuation of the
      postperfusion syndrome.

PMID- 9236348
TI  - Results of valve replacement with mechanical and biological prostheses in chronic
      renal dialysis patients.
AB  - BACKGROUND: Whether biological or mechanical valves should be used in patients on
      chronic dialysis therapy remains to be clearly defined. METHODS: A retrospective
      review was performed on 19 consecutive patients from our institution with end
      stage renal disease on chronic peritoneal or hemodialysis undergoing aortic (n =
      12), mitral (n = 5), or aortic-mitral (n = 2) valve replacement. RESULTS: The 9
      biological and 10 mechanical valve patients had similar ages (56.5 versus 56.6
      years) and cardiovascular risk factors. The overall estimated Kaplan-Meier
      survival was 60% +/- 12% at 12 months and 42% +/- 14% at 60 months. Mechanical
      valve patients had a significantly higher rate of postoperative cerebrovascular
      accidents or bleeding complications (10/10 versus 0/9; chi 2 = 17.0; p < 0.001).
      No subsequent reoperations were required for biological valve failure at a mean
      follow-up of 32 +/- 53 months. CONCLUSIONS: These results demonstrate that in
      patients with end-stage renal disease, use of mechanical valves is associated
      with significant risk of complications, whereas biological valve failure from
      prosthetic dysfunction is unusual. Overall survival is poor in both groups of
      patients. Therefore, preference should be given to biological valve instead of
      mechanical valve prostheses in patients on chronic renal dialysis.

PMID- 9236349
TI  - Fast-track cardiac surgery in a Department of Veterans Affairs patient
      population.
AB  - BACKGROUND: "Fast-track" (FT) cardiac surgery is popular in the private and
      university sectors. This study was designed to examine its safety and efficacy in
      the Department of Veterans Affairs elderly, male patient population, a population
      with multiple comorbid risk factors, often decreased social functioning, and
      impaired support systems. METHODS: Time to extubation, hospital length of stay,
      perioperative morbidity, and mortality were studied in two consecutive cohorts
      undergoing cardiac operations requiring cardiopulmonary bypass before (pre-FT: n
      = 255, January 1992 to September 1993) and after (FT: n = 304, October 1993 to
      October 1995) institution of an FT protocol at a university-affiliated teaching
      Department of Veterans Affairs medical center. Preoperative risk factors,
      including a Department of Veterans Affairs risk-adjusted estimate of operative
      mortality, and perioperative surgical and anesthetic processes of care were
      evaluated. RESULTS: The mean Department of Veterans Affairs risk estimate of
      perioperative mortality was not different between the pre-FT and FT cohorts (3.5%
      versus 3.7%, p = 0.13). In the FT cohort, median time to extubation decreased
      significantly (19.2 versus 10.2 hours; p < 0.001) along with median surgical
      intensive care unit stay (96 versus 49 hours; p < 0.001) and total postoperative
      length of stay (222 versus 167 hours; p < 0.001). Median postoperative day of
      hospital discharge decreased from day 10 to 7 (p < 0.001). One patient (0.3%)
      required emergent reintubation directly related to early extubation. Reintubation
      for medical reasons was unchanged between pre-FT and FT groups (6.3% versus 5.0%;
      p = 0.48). Postoperative morbidity was similar between groups except for
      nosocomial pneumonia, the rate of which decreased significantly in the FT cohort
      (14.7% versus 7.3%; p < 0.005). Thirty-day (3.9% versus 4.6%; p = 0.69) and 6
      month mortality (6.7% versus 6.9%; p = 0.91) were unchanged. CONCLUSIONS: An FT
      cardiac surgery protocol has been instituted in a university-affiliated teaching
      Department of Veterans Affairs medical center, with decreased length of stay and
      no significant increase in postoperative morbidity, 30-day mortality, or 6-month
      mortality. It was associated with a lower rate of nosocomial pneumonia, a finding
      that must be validated in a prospective study.

PMID- 9236350
TI  - Management of left ventricular assist device infection with heart
      transplantation.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to
      heart transplantation (HT). Infection of the LVAD in this patient population
      represents a serious complication, as simple LVAD removal or delaying HT may
      result in death. To improve outcomes in this group of patients, we performed HT
      in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD
      implantation followed by HT. Ten underwent HT in the absence of LVAD infection
      (group 1); and 8, in the presence of LVAD infection (group 2). All patients were
      treated similarly except for modification of immunosuppression in group 2
      patients. RESULTS: Infectious and noninfectious complications were equivalent
      between the two groups. There was no difference between groups in regard to
      intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8),
      wound complications (three versus none), and mean length of hospital stay after
      HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too
      seriously ill to allow LVAD removal or delay of HT. Transplantation in the face
      of infection is an effective treatment option.

PMID- 9236351
TI  - Phrenic nerve injury after coronary artery grafting: is it always benign?
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of phrenic nerve
      injury (PNI) occurring during coronary artery bypass grafting in patients with
      major chronic obstructive pulmonary disease (COPD). METHODS: Over a 42-month
      period, 1,303 patients underwent primary coronary artery bypass grafting. Sixty
      seven (5.14%) had major COPD, and 29 (43.3%) of these 67 sustained PNI (group I).
      These patients were matched for age and ejection fraction with 29 CABG patients
      with COPD but without PNI (group II), 29 patients without COPD but with PNI
      (group III), and 29 patients with neither COPD nor PNI (group IV). The groups
      were compared on the basis of preoperative and operative factors and immediate
      and midterm morbidity and mortality. RESULTS: There were no significant
      differences between the groups with respect to hypertension, diabetes, ejection
      fraction, number of grafts, internal mammary artery use, cardiopulmonary bypass
      time, and ischemic time. Postoperatively, group I had a longer total
      hospitalization (group I, 11.7 days; group II, 7.8 days; group III, 7.8 days; and
      group IV, 6 days; p = 0.0001) and stay in the intensive care unit (I, 3.6 days;
      II, 2.2 days; III, 2.1 days; and IV, 1.2 days; p = 0.0023). More patients in
      group I required reintubation (I, 37.9%; II, 3.4%; III, 6.9%; and IV, 0%; p <
      0.0001). Mean follow-up was 32.8 months (range, 7 to 48 months). Group I had more
      hospital readmissions (I, 78; II, 50; III, 61; and IV, 28; p < 0.007) and lower
      cumulative survival (I, 60.6%; II, 93%; III, 96.8%; and IV, 100%; p < 0.0015)
      compared with the other groups. CONCLUSIONS: In patients with COPD, PNI during
      coronary artery bypass grafting has a major negative impact on immediate and
      midterm results.

PMID- 9236352
TI  - Fate of trileaflet equine pericardial extracardiac conduit used for the
      correction of anomalies having pulmonic ventricle-pulmonary arterial
      discontinuity.
AB  - BACKGROUND: External conduits used for the repair of congenital heart diseases
      having discontinuity between the pulmonic ventricle and the pulmonary artery
      still carries a high risk of reoperation. Between June 1983 and June 1992,
      handmade equine pericardial conduit with fabricated trileaflet valve had been the
      conduit of choice in our institute. The aim of this study is to clarify the
      temporal sequence of conduit obstruction in this material and to formulate the
      optimal surgical strategies for this disease entity. METHODS: One hundred forty
      three patients have undergone extracardiac conduit repair using this conduit.
      Postoperative catheterization performed within 2 months showed pulmonary to
      systemic ventricular systolic pressure ratio of 0.57 +/- 0.17 with the pressure
      gradient between pulmonic ventricle and pulmonary artery of 21.1 +/- 17.2 mm Hg.
      In 63 patients among the survivors, a series of Doppler two-dimensional
      echocardiographic images could be clearly obtained. RESULTS: Moderate-to-severe
      degree of pulmonary insufficiency represented only 3.2% of all cases within 3
      months, which rapidly increased to 14.3% at 1 to 3 years and 32.8% at 3 to 5
      years. However, the rate of increase of pulmonary insufficiency diminished beyond
      5 years with 34.9% at 5 to 7 years and 40.0% at 7 to 9 years. Estimated pressure
      gradient calculated by Bernoulli's equation applied in the same patient subset
      was 4.1 +/- 7.9 mm Hg within 3 months, which progressively increased to 7.1 +/-
      11.8 mm Hg at 1 to 3 years, 21.0 +/- 24.0 mm Hg at 3 to 5 years, 40.2 +/- 25.9 mm
      Hg at 5 to 7 years, and 71.3 +/- 34.0 mm Hg at 7 to 9 years. Among patients with
      a pressure gradient across the conduit of more than 40 mm Hg at follow-up
      catheterization, the primary cause of the obstruction was attributed to
      degeneration of the valve in 7 patients, whereas sternal compression was strongly
      suspected as the primary cause in the other 8 patients. Intimal peel was not
      obvious in the excised specimens. CONCLUSIONS: Degeneration of the valve in the
      equine pericardial conduit became prominent at 3 to 5 years after the operation,
      whereas the pressure gradient across the conduit continued to progress
      thereafter. A thick and hardened valve from degeneration and varying degrees of
      external compression by the sternum were delineated at the site of stenosis.

PMID- 9236353
TI  - Facing the era of minimally invasive coronary grafting: current results of
      conventional bypass grafting for single-vessel disease.
AB  - BACKGROUND: The concepts of minimally invasive coronary artery bypass grafting
      have gained increasing attention and interest from cardiac surgeons. Operations
      through small incisions are mostly applied to patients with less extensive
      coronary disease, mostly single-vessel disease. The aim of this study was to
      identify a baseline level of conventional coronary bypass grafting for this group
      of patients, particularly with regard to surgical complications and immediate
      results. METHODS: Of 3,637 consecutive patients undergoing coronary artery bypass
      grafting during the period 1989 to 1995, 99 patients (2.7%) were identified to
      have single-vessel disease. The preoperative and hospital data of this subset of
      patients were analyzed. RESULTS: The left internal mammary artery was grafted in
      96% of the patients, either as single graft to the left anterior descending
      artery or sequentially to the left anterior descending artery and a diagonal
      branch. Additional vein grafts were placed in 36 patients, and the mean number of
      distal anastomoses was 1.6 +/- 0.6. Mean ischemic time and cardiopulmonary bypass
      time were 15.3 +/- 9.6 minutes and 29.0 +/- 12.5 minutes, respectively. The
      patients were weaned from the ventilator 1.5 +/- 0.8 hours postoperatively, and
      all patients were out of bed the morning after the operation. No patients
      required homologous blood or plasma transfusions. The morbidity rate was low, and
      all patients survived. CONCLUSIONS: For this highly selected group of patients,
      coronary artery bypass grafting based on median sternotomy, cardiopulmonary
      bypass, and cardioplegic arrest carries a very high rate of immediate success.
      Such data may be useful as a baseline when considering the costs and benefits of
      new surgical procedures.

PMID- 9236354
TI  - Effect of cardiopulmonary bypass perfusion protocols on gut tissue oxygenation
      and blood flow.
AB  - BACKGROUND: Previous studies in patients undergoing cardiopulmonary bypass (CPB)
      have documented gastric mucosal hypoperfusion and hypoxia. This study examines
      the influence of the CPB protocol on the adequacy of gut blood flow and
      oxygenation. METHODS: Twenty-four patients were prospectively randomized into one
      of four CPB groups: nonpulsatile hypothermic (NP 28); pulsatile hypothermic (P
      28); non-pulsatile normothermic (NP 37); and pulsatile normothermic (P 37).
      Gastric wall blood flow was assessed using laser Doppler flow measurement and
      gastric mucosal oxygenation (intramucosal pH), using tonometry. RESULTS: After 10
      minutes of CPB, the NP 28 group had the greatest reduction in gastric wall blood
      flow (-60.6% +/- 3.8%) compared with baseline (p < 0.05). Thirty minutes into
      CPB, the P 37 group had less gastric mucosal hypoperfusion (-9.7% +/- 10.3%) than
      the NP 28 patients (-53.0% +/- 8.6%; p < 0.05). All groups showed a hyperemic
      response immediately after CPB. No significant differences between the four
      groups were found for gastric mucosal oxygenation during or after CPB. A
      progressive decline occurred in this variable during the period 3 to 4 hours
      after CPB. At this time, total-body oxygen consumption and extraction were at
      their maximum. CONCLUSIONS: This study found that perfusion protocol can
      influence mucosal blood flow, but other overriding factors that operate during
      and after CPB act to cause mucosal hypoxia. These findings, particularly the
      timing of mucosal hypoxia, may have implications for centers contemplating early
      extubation or "fast tracking" of patients after CPB.

PMID- 9236355
TI  - Thoracoscopic transmyocardial laser revascularization.
AB  - BACKGROUND: Transmyocardial laser revascularization is a promising surgical
      technique used to treat nonreconstructable ischemic heart disease. Recent
      clinical data show that this technique improves the regional perfusion of
      ischemic myocardium and reduces angina. Presently, transmyocardial laser
      revascularization requires an open, lateral thoracotomy. We report here the use
      of thoracoscopic techniques to perform transmyocardial laser revascularization in
      a closed chest fashion. METHODS: Five Yorkshire farm pigs underwent left chest
      thoracoscopic exploration and pericardiotomy. A specialized laser handpiece then
      was introduced into the chest and thoracoscopic transmyocardial laser
      revascularization was performed (one channel per square centimeter) using an 800
      W CO2 laser. RESULTS: Video analysis and gross pathology revealed that the
      anatomic area accessible to thoracoscopic transmyocardial laser revascularization
      included the entire left ventricular free wall distributions of the left anterior
      descending, left circumflex, and posterior descending arteries, from base to
      apex. Standard hematoxylin and eosin staining confirmed the creation of complete
      and patent 1-mm-diameter transmural channels throughout these distributions.
      CONCLUSION: We have shown that transmyocardial laser revascularization can be
      performed effectively and safely by thoracoscopy, and that this less invasive
      technique may reduce morbidity and provide a more cost-effective alternative
      therapy for nonreconstructable ischemic heart disease.

PMID- 9236356
TI  - Teletronics 330-801 atrial lead extraction via the subclavian approach.
AB  - BACKGROUND: The Telectronics 330-801 atrial J (801) lead was recalled after
      reports implicated lead fracture/retention wire protrusion in patient mortality
      and morbidity. Recent reports suggest that 801 lead extraction may be associated
      with substantial morbidity and, possibly, excess mortality. We hypothesized that
      the 801 lead could be extracted using the subclavian approach with a high success
      rate and acceptable morbidity. METHODS: We analyzed the clinical outcomes in 60
      consecutive patients who underwent 801 lead extraction. RESULTS: Sixty patients
      (34 women) with a mean age of 67 +/- 14.8 years had 18 class I, 13 class II, and
      29 class III fractures. The lead age was 39 +/- 17 months. The subclavian
      approach was successful in 58 of 60 patients (96%). Complications, three major
      and eight minor, occurred in 10 of 60 patients (16%). All complications were
      successfully treated. There were no deaths. Only concurrent ventricular lead
      extraction was associated with complications (p = 0.008 by Fisher's exact test).
      CONCLUSIONS: Telectronics 801 leads can be successfully extracted using the
      subclavian approach with acceptable short-term morbidity, low mortality, and
      excellent long-term results.

PMID- 9236357
TI  - Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of
      pulmonary metastases.
AB  - BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to
      evaluate long-term survival after isolated lung perfusion with doxorubicin.
      METHODS: In the model development study, on day 0, two groups of F344 rats (n =
      15) underwent transient right pulmonary artery occlusion for either 5 or 10
      minutes at the time of intravenous injection of methylcholantrene-induced sarcoma
      cells. On day 14, all animals were sacrificed and lung nodules counted. In the
      survival study, on day 0, 21 rats received intravenous injection of sarcoma cells
      with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats
      underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats
      underwent perfusion with buffered Hespan; six untreated rats were studied as
      controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute
      pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion
      resulted in a tumor-free right lung in all animals. In the survival study, all
      animals in the Hespan and control groups died of massive tumor replacement of the
      left lung, with median survival times of 20 and 18 days, respectively. The median
      survival time of 36 days for the animals undergoing isolated lung perfusion with
      doxorubicin was significantly longer (p < 0.00001). The left lung of two of the
      doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung
      perfusion with doxorubicin results in a durable response and prolongs survival in
      the treatment of experimental sarcoma pulmonary metastases.

PMID- 9236358
TI  - Induction chemoradiotherapy followed by esophagectomy in patients with carcinoma
      of the esophagus.
AB  - BACKGROUND: Induction chemoradiotherapy followed by esophagectomy may provide
      results superior to those of single-modality treatment in patients with
      esophageal cancer. The purpose of this study was to review our experience with
      this approach for esophageal cancer. METHODS: From 1988 to 1996, 166 consecutive
      patients with esophageal cancer were evaluated; 66 entered a protocol of
      chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy)
      followed by esophagectomy. Fifty-four patients completed the protocol. RESULTS:
      Toxicity associated with induction chemoradiotherapy was minimal. The actuarial
      survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The
      pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month
      survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%,
      35%, and 23%. The difference in survival between pCR and non-pCR patients was not
      significant (p = 0.13), but the difference in recurrence-free survival was
      significant (p = 0.007). CONCLUSIONS: This well-tolerated protocol resulted in a
      high pCR. Trimodality treatment for esophageal cancer may provide long-term
      survival in some patients regardless of their pCR status.

PMID- 9236359
TI  - Survival and prognosis after pneumonectomy for lung cancer in the elderly.
AB  - BACKGROUND: The number of elderly patients with lung cancer is increasing. This
      study was undertaken to assess the validity of pneumonectomy for the treatment of
      lung cancer in this patient group. METHODS: Twenty-seven patients 70 years old or
      older (elderly group) and 95 patients younger than 70 years (younger group) who
      underwent pneumonectomy between January 1985 and March 1996 formed the study
      group. In the elderly group, 22 patients had squamous cell carcinoma, 2 had
      adenocarcinoma and 3, small cell carcinoma; 1 patient was in postoperative stage
      I, 4 patients were in stage II, 14 in stage IIIA, 5 in stage IIIB, and 3 in stage
      IV of the disease. The only significant differences in patient characteristics
      between the two groups were the percentage of patients undergoing right
      pneumonectomy and the percentage of patients receiving chemotherapy or
      radiotherapy within 3 months before or after operation or both times. RESULTS:
      The prognosis for the elderly group was comparable to that of the younger group
      for all stages of the disease; the overall 5-year survival rate was 30.5% for the
      younger group and 11.5% for the elderly group. However, operation-associated
      mortality was significantly higher in the elderly group (22.2% versus 3.2%; p <
      0.005). The prognosis was better for patients with a centrally located tumor than
      a peripheral tumor in both groups [13.5% versus 2.0% in the elderly group and
      46.7% versus 5.2% (p < 0.01) in the younger group] and significantly better for
      patients having a left pneumonectomy than a right pneumonectomy in the younger
      group (46.7% versus 5.2%; p < 0.01) but not in the elderly group (13.7% versus
      22.2%). Adjuvant treatment did not have any beneficial effect on the prognosis in
      either group. CONCLUSIONS: Pneumonectomy for lung cancer in elderly patients
      appears to be justified because the outcome in our study was comparable with that
      for the younger patients. However, it should be performed only in carefully
      selected patients because of the increased operative risk.

PMID- 9236360
TI  - Successful tracheal autotransplantation with two-stage approach using the greater
      omentum.
AB  - BACKGROUND: Although many studies on reconstruction of extensive circumferential
      tracheal defects with a segmental trachea have been done, up to date, no reliable
      and satisfactory tracheal transplantation procedure has been developed. We
      conducted this experiment to investigate feasibility and efficacy of a staged
      tracheal transplantation approach for tracheal reconstruction. METHODS: Twelve
      dogs were divided equally into groups I and II. A segment of cervical tracheas
      (six rings) was harvested as an autograft and implanted heterotopically into the
      greater omentum. Two weeks later, the autografts with their omental pedicles were
      transplanted orthotopically to the cervical (group I) or the thoracic portion of
      the trachea (group II). Bronchoscopic examination were performed monthly during a
      5-month follow-up period. After sacrificing the dogs, we had the grafts examined
      macroscopically and microscopically. RESULTS: The dogs of both groups survived
      well until the end of the follow-up. No abnormal findings were observed through
      bronchoscopy. The grafts had normal appearance, without shrinkage, granulation,
      or necrosis by postmortem gross examination. Histologic examination showed the
      structures of the grafts were intact. CONCLUSIONS: We conclude that the two-stage
      tracheal transplantation approach using the greater omentum is feasible, and can
      facilitate the survival of a tracheal graft as well.

PMID- 9236361
TI  - Retrieval by other procurement teams provides favorable lung transplantation
      outcome.
AB  - BACKGROUND: During the last 4 years, we have increasingly used lungs retrieved by
      other procurement teams. We therefore investigated whether the use of those lungs
      affected the outcome of lung transplantation. METHODS: We analyzed the results of
      159 consecutive lung transplantations performed at our institution between July
      1, 1992, and December 31, 1995. The transplants were divided into three groups:
      distant donor lungs retrieved by our team (DB group, n = 68); distant donor lungs
      retrieved by other teams (DX group, n = 46); and local donor lungs retrieved by
      our team (LB group, n = 44). One transplantation with a local donor lung
      retrieved by another team was excluded from the analysis. RESULTS: No significant
      differences were noted between the three groups in alveolar-arterial oxygen
      gradient immediately after transplantation (DB group, 359 +/- 18 mm Hg; DX group,
      329 +/- 23 mm Hg; LB group, 327 +/- 20 mm Hg) and at 24 hours; days on
      ventilator; days in the intensive care unit; length of hospital stay; 30-day
      mortality; and actuarial 1-year survival (DB group, 81%; DX group, 87%; LB group,
      89%). CONCLUSIONS: The use of donor lungs retrieved by other teams achieves an
      equivalently satisfactory outcome after lung transplantation as lungs retrieved
      by our team.

PMID- 9236362
TI  - Postoperative pain and superficial abdominal reflexes after posterolateral
      thoracotomy.
AB  - BACKGROUND: Posterolateral thoracotomy can produce stretching of/or damage to the
      intercostal nerves and their branches. To assess intercostal nerve impairment
      after operation, we measured the superficial abdominal reflexes, which are
      mediated, at least in part, by the most inferior intercostal nerves. METHODS:
      Using electrophysiologic techniques, we made recordings from the left and right
      abdominal walls to study the responses evoked by mechanical stimulation of the
      skin after operation. In addition, we assessed postoperative pain intensity
      according to a numeric rating scale and recorded postoperative opioid dose.
      RESULTS: We found that the patients with complete disappearance of the
      superficial abdominal reflexes experienced more severe postoperative pain than
      those in whom the reflexes were maintained. Moreover, opioid treatment was less
      effective in the patients with no reflexes postoperatively. CONCLUSIONS: Our
      findings show a strict correlation between pain intensity after posterolateral
      thoracotomy and absence of abdominal reflexes. We suggest that the higher pain
      intensity together with the absence of reflexes may be due to intercostal nerve
      impairment, be it anatomic or functional, and thus to a larger neuropathic
      component of postoperative pain. This finding may be used as a predictor of
      patients with high analgesic requirements.

PMID- 9236363
TI  - Video-assisted thoracic surgery: has technology found its place?
AB  - BACKGROUND: Since the introduction of minimally invasive surgical techniques in
      thoracic surgery in 1990, video-assisted thoracic surgery (VATS) has become the
      approach for many thoracic operations. The role of VATS has slowly evolved but
      has not been clearly defined. To better understand the role of VATS, we undertook
      a survey of practicing thoracic surgeons. METHODS: A questionnaire was sent to
      members of the General Thoracic Surgery Club asking the role of VATS in their
      practice and their opinions regarding appropriate applications, advantages, and
      limitations of the approach. RESULTS: Two hundred of the 229 members (87.3%)
      responded to the questionnaire. In this largely academic (66.3%) group of
      thoracic surgeons, 72% of whom had more than 10 years experience in general
      thoracic surgery, VATS was the preferred approach (> 50% response) for the
      management of pleural disease, lung biopsy, recurrent pneumothorax, and
      sympathectomy. A majority of respondents thought that VATS was an acceptable
      approach for the diagnosis of the indeterminate pulmonary nodule and of anterior
      and posterior mediastinal masses, and for the management of early empyema,
      clotted hemothoraces, secondary pneumothorax, limited lung cancer treatment, and
      benign esophageal disease. Video-assisted thoracic surgery was thought to be
      unacceptable or investigational by a majority for thymectomy, lobectomy, and lung
      volume reduction operations. Video-assisted thoracic surgery still represents
      only a small portion of the thoracic procedures performed, but there is a gradual
      increase in its rate of use, although 38.1% expressed concern regarding overuse.
      The main limitation was thought to be in the management of oncologic disease.
      CONCLUSIONS: It appears that VATS is a valuable addition to the practice of
      thoracic surgery, but significant limitations exist. Although there appear to be
      many specific indications defined, there is still a significant evolutionary
      component.

PMID- 9236364
TI  - Establishment of an experimental intrapulmonary tumor nodule model.
AB  - BACKGROUND: A pulmonary tumor model is necessary to study the biology and therapy
      of lung cancer. Methods to establish a solitary intrapulmonary nodule are not
      well defined. Two methods for solitary intrapulmonary tumor nodule development in
      the Fischer rat are described. METHODS: Methylcholanthrene-induced sarcoma cell
      suspensions were introduced into lung parenchyma of Fischer rats via limited
      thoracotomy and lung puncture, or instilled into a distal airway after tracheal
      puncture and catheterization. Intrapulmonary tumor location, implantation
      mortality, procedure length, and animal survival were recorded. RESULTS: Single
      pulmonary nodules developed at the implanted position in 100% (n = 320) and 95%
      (62/65) of animals after direct injection into the pulmonary parenchyma or via
      tracheal puncture and instillation. Operative mortality was 2% and 5% via lung or
      tracheal implantation, respectively. Less than 5 minutes was required for each
      implantation. Mean survival time was 24 +/- 2 and 26 +/- 6 days after lung or
      tracheal implantation in animals allowed to survive until tumor-induced death.
      CONCLUSIONS: These easily performed, reproducible methods of establishing
      solitary intrapulmonary tumors are useful tools for lung cancer research.

PMID- 9236365
TI  - Long-term complications of extraperiosteal plombage.
AB  - BACKGROUND: As soon as complications due to migration of extraperiosteal plombage
      material had been documented, early removal became the rule. Some patients who
      have escaped this rule may still present with long-term complications. METHODS:
      Since 1980, 14 patients aged 54 +/- 10 years were admitted 28 +/- 11 years after
      collapse therapy. Eight presented with signs of infection, 4 with hemoptysis, and
      2 with periscapular pain. Vascular erosion, suspected in 3 patients, was
      demonstrated with angiograms in 1. RESULTS: Ablation of the material was combined
      with excision of the devitalized ribs in 13 patients. Femorofemoral bypass was
      used in 2 patients for repair of an aortic erosion. Single ablation of
      subcutaneously migrated material was performed in a poor-risk patient. Operative
      bleeding was moderate except in 2 patients; 1 of them died intraoperatively
      during repair of an aortic erosion. A second patient died postoperatively with a
      massive pulmonary embolus on day 11. Infection was diagnosed in 8 patients
      (Mycobacterium tuberculosis, 4; and pyogens, 4). Operative outcome was
      satisfactory in all 12 operative survivors. A single patient presented with an
      infected apical space at 1 year and underwent complementary resection of the
      first rib. CONCLUSIONS: We recommend routine ablation of any residual plombage
      material whenever operative risk is acceptable because of the high incidence of
      spontaneous complications.

PMID- 9236366
TI  - Unilateral giant bullous emphysema with placental transmogrification of the lung.
AB  - A case of severe unilateral bullous emphysema in an otherwise healthy young man
      is presented to highlight a rare histologic variant termed "placental
      transmogrification of the lung." The etiology is unknown, but operation has been
      curative in the small number of cases reported.

PMID- 9236367
TI  - Atrially based pericardial tunnel for central pulmonary artery construction.
AB  - Discontinuity of central intrapericardial pulmonary arteries requires
      reconstruction of a pulmonary artery confluence before cavopulmonary connection,
      whether this connection be by bidirectional Glenn or Fontan procedure.
      Reconstruction of the central pulmonary arteries has previously been described
      using material of poor or no growth potential. A method is described for central
      pulmonary artery reconstruction that provides growth potential and is based on
      previous experience with Fontan lateral tunnel construction.

PMID- 9236369
TI  - Congenital bilateral coronary-to-pulmonary artery fistulas.
AB  - Rare, congenital bilateral coronary-to-pulmonary artery fistulas in an older
      woman, one originating from the proximal right coronary artery and the other from
      a distal left main coronary artery and draining to the proximal main pulmonary
      artery, were successfully dissected, identified, and ligated proximally and also
      closed distally on a beating heart with cardiopulmonary bypass standby.

PMID- 9236368
TI  - Closure of a bronchopleural fistula using decalcified human spongiosa and a
      fibrin sealant.
AB  - Bronchopleural fistulas associated with empyema can occur as a life-threatening
      sequelae after pulmonary resection, most frequently occurring after
      pneumonectomy. With the use of the flexible bronchoscope, the bronchopleural
      fistula of a 62-year-old critically ill woman was permanently sealed with a
      fibrin sealant and a small section of demineralized human spongiosa. Closure of
      bronchopleural fistulas with the application of fibrin sealant plus human
      spongiosa may offer a valuable addition to the armament of therapeutic
      alternatives.

PMID- 9236370
TI  - Correction of anomalous systemic venous drainage in heterotaxy syndrome.
AB  - A 3-month-old patient with heterotaxy syndrome, complex intracardiac
      malformations, and severe heart failure underwent surgical correction. Anatomy
      included an interrupted inferior vena cava with hemiazygous continuation to a
      persistent left superior vena cava draining to the left atrium. The presence of
      partial anomalous pulmonary venous drainage precluded an intraatrial baffle.
      Systemic venous reconstruction was achieved using the left atrial appendage along
      with an intracardiac repair of the other defects.

PMID- 9236371
TI  - Mediastinoscopic extirpation of mediastinal ectopic parathyroid gland.
AB  - We report a case of a 50-year-old man with hyperparathyroidism secondary to
      chronic renal failure who underwent extirpation of a mediastinal ectopic
      parathyroid gland by a transcervical approach under mediastinoscopy. This
      procedure provides an excellent approach to the mediastinal ectopic parathyroid
      gland, and is less invasive than median sternotomy or thoracotomy.

PMID- 9236372
TI  - Rupture of the atrial septum and tricuspid valve after blunt chest trauma.
AB  - A previously fit 19-year-old male driver was involved in an unrestrained, head-on
      collision. Transesophageal echocardiography revealed rupture of the chordae
      subtending both leaflets of the tricuspid valve with severe tricuspid
      regurgitation and disruption of the interatrial septum. When cardiac injury is
      suspected after blunt chest trauma, transesophageal echocardiography facilitates
      appropriate management as it provides safe, rapid, and accurate diagnostic
      images.

PMID- 9236373
TI  - Thoracoabdominal fenestration for aortic dissection with ischemic colonic
      perforation.
AB  - Previous attempts at repair of aortic dissection complicated by intestinal
      infarction requiring concomitant bowel resection have been fatal. Presented is a
      case of distal aortic dissection resulting in colonic infarction and perforation.
      Thoracoabdominal aortic fenestration with concomitant right hemicolectomy was
      successful. In patients with aortic dissection complicated by mesenteric
      ischemia, we recommend urgent graft replacement of the thoracoabdominal aorta
      when feasible. When peritoneal contamination precludes the use of prosthetic
      grafts, thoracoabdominal fenestration is an effective option.

PMID- 9236374
TI  - Pulmonary hypertension caused by medial hypertrophy associated with aortic
      stenosis and preductal coarctation.
AB  - A 7-month-old female infant with aortic stenosis, preductal coarctation, and
      pulmonary hypertension underwent operation. Intraoperative lung biopsy revealed
      marked medial hypertrophy of the pulmonary arterioles. This histopathology is
      compatible with persistent pulmonary hypertension in the newborn. She is alive
      about 5 years after the operation, but pulmonary hypertension remains. The
      pathogenesis is discussed.

PMID- 9236375
TI  - Acute submucosal esophageal hemorrhage.
AB  - Two cases of acute submucosal esophageal hemorrhage are reported. This condition
      is uncommon and presents an urgent diagnostic dilemma. Its presentation,
      diagnosis, and management are reviewed. The underlying pathology and causative
      factors are researched and clarified. Conservative management is safe and
      effective.

PMID- 9236376
TI  - Ross-Konno procedure with interrupted aortic arch repair in a premature neonate.
AB  - A 1,700-g premature baby who presented with interrupted aortic arch type B,
      hypoplastic aortic annulus, severe subaortic stenosis, and large ventricular
      septal defect underwent successful surgical repair. A Ross-Konno operation was
      used to address the left ventricular outflow tract obstruction, hypoplastic
      aortic annulus, and ventricular septal defect. The interruption was repaired with
      a direct anastomosis.

PMID- 9236377
TI  - Inflammatory aneurysm of the ascending aorta and aortic arch.
AB  - Inflammatory aortic aneurysms are distinct clinical entities seen mostly in the
      infrarenal abdominal aorta and rarely in the descending thoracic aorta. We
      present the case of a 61-year-old woman with an inflammatory aortic aneurysm of
      the ascending aorta and aortic arch.

PMID- 9236378
TI  - Repair of aortoesophageal fistula after aortic grafting.
AB  - This report describes repair of an aortoesophageal fistula caused by a previously
      placed thoracic aortic graft. The diagnosis was made by esophagoscopy. The repair
      consisted of femoral-to-femoral cardiopulmonary bypass, excision of the old
      graft, placement of a new graft, esophagectomy, cervical esophagostomy,
      gastrostomy, and later reconstruction by cervical esophagogastrostomy.

PMID- 9236379
TI  - Successful thrombolysis after prosthetic pulmonary valve obstruction under
      aspirin monotherapy.
AB  - In a 22-year-old woman with recent onset of left-sided chest pain and exertional
      dyspnea, echocardiography revealed obstruction of a St. Jude Medical bileaflet
      prosthetic valve (size 23 mm) in the pulmonary position. Oral anticoagulation had
      been replaced for the previous 7 years by aspirin as the sole antithrombotic
      treatment. The valve had been inserted 16 years ago for pulmonary atresia. Valve
      function was restored by systemic application of 9 million units of urokinase.

PMID- 9236380
TI  - Blunt intrapericardial rupture of the pulmonary artery in a surviving patient.
AB  - Blunt chest trauma can produce a number of potentially lethal injuries, including
      pulmonary artery rupture. Survivors of pulmonary artery injuries are rare. Most
      previously reported surviving patients presented with hemothorax from a hilar
      injury. We report a patient who survived a blunt rupture of the intrapericardial
      portion of the pulmonary artery and thus presented with pericardial tamponade.
      The interventions that led to her survival are discussed.

PMID- 9236381
TI  - Punch pulmonary valvectomy: another alternative to treat critical pulmonary
      stenosis.
AB  - For neonates with severe valvar stenosis, or valvar pulmonary atresia with an
      imperforate pulmonary valve, we present a simple but effective closed procedure
      using a specially designed valvectomy punch. Seven neonates, who were not
      suitable for any type of transcatheter procedure, were treated. There were two
      late deaths, neither directly related to the operation; 4 patients are developing
      well. This approach using the valvectomy punch is a fast, safe, and effective
      procedure.

PMID- 9236382
TI  - Endoscopic saphenous vein harvesting.
AB  - Although the use of arterial conduit has decreased the amount of saphenous vein
      required for routine coronary artery bypass grafting, the saphenous vein as a
      bypass conduit remains an essential component of most practices. We describe the
      technique of endoscopic vein harvest that, in our initial experience with 30
      patients, has improved patient satisfaction and decreased the complications
      associated with traditional harvest techniques.

PMID- 9236383
TI  - Tricuspid valve repair with the Cosgrove-Edwards Annuloplasty System.
AB  - The technique of tricuspid valve repair with the Cosgrove-Edwards Annuloplasty
      System is described. This system provides a measured plication of the tricuspid
      valve annulus with a technique that is easily reproducible and permits
      physiologic motion of the tricuspid annulus.

PMID- 9236384
TI  - Transaxillary minithoracotomy for modified Blalock-Taussig shunt.
AB  - A technique that allows construction of a modified Blalock-Taussig shunt using a
      polytetrafluoroethylene graft in neonates and infants through an axillary
      vertical minimal access thoracotomy is described. It is a simple, safe,
      cosmetically acceptable, and efficient approach even when used during emergency
      situations. It was successfully performed in 5 neonates and infants.

PMID- 9236385
TI  - Preservation of anterior and posterior leaflet in mitral valve replacement with a
      tilting-disc valve.
AB  - An operative technique for mitral valve replacement with preservation of chordae
      tendineae to both the anterior and posterior leaflets is described. The anterior
      mitral valve leaflet is completely detached from the annulus and divided into
      three to four islands of tissue, each with attached chordae tendineae. These
      islands are transposed under the posterior leaflet and secured with 4-0
      polypropylene sutures. The posterior leaflet is completely preserved with no
      division or manipulation. This technique allows safe implantation of tilting-disc
      or bileaflet prostheses with excellent preservation of left ventricular function.

PMID- 9236386
TI  - Modified biatrial approach for the surgical excision of left atrial myxomas.
AB  - The biatrial approach generally has been accepted as the method for excision of
      atrial myxoma, having the advantages of identifying the site of attachment,
      inspection of the four cardiac chambers, and adequate irrigation. A technique
      that uses this approach, adding safety and completeness of removal of left atrial
      myxomas attached to the septum, is described.

PMID- 9236387
TI  - Necrotizing soft tissue infections of the chest wall.
AB  - BACKGROUND: Necrotizing soft tissue infections of the chest wall are uncommon,
      and they have received little discussion in the medical literature. METHODS: We
      performed a collective review of the literature to summarize information on
      etiology, prevention, treatment, complications, and outcome of chest wall
      necrotizing soft tissue infections. Manual, Medline, and Current Contents
      searches of the English-language medical literature were done. RESULTS: There
      were 9 reported cases of necrotizing soft tissue infection of the chest wall.
      Eight were complications of invasive procedures and operations. Tube thoracostomy
      for empyema (4 patients) was the most common antecedent procedure. Excessive soft
      tissue dissection during chest tube insertion was implicated in the genesis of
      these infections. Necrotizing infections complicated esophageal operations in 2
      patients. Overall mortality was 89%. Only 3 of the 9 patients underwent early and
      adequate debridement. Chest wall stability and wound reconstruction were
      problematic in patients who survived the initial septic illness. CONCLUSIONS:
      Necrotizing soft tissue infections of the chest wall are highly lethal infections
      that require urgent and aggressive debridement. Diagnostic delay and inadequate
      debridement are common reasons for treatment failure. Repetitive surgical
      debridement is often needed to control sepsis. Wound closure is challenging in
      patients who survive the initial septic phase of their illness.

PMID- 9236389
TI  - Extracardiac total cavopulmonary connection without cardiopulmonary bypass.

PMID- 9236390
TI  - Talc slurry versus talc insufflation revisited.

PMID- 9236391
TI  - Minimally invasive coronary artery bypass grafting.

PMID- 9236392
TI  - Controlled limb reperfusion in patients having cardiac operations.

PMID- 9236394
TI  - "Heartflip" technique for exposing the circumflex territory.

PMID- 9236393
TI  - Expandable stents in esophageal malignancy.

PMID- 9236395
TI  - Heart transplantation in septuagenarians.

PMID- 9236396
TI  - AIDS-related pneumothorax.

PMID- 9236397
TI  - Antegrade cardioplegia pressure monitoring.

PMID- 9236398
TI  - Innominate and subclavian arteries as an inflow of free arterial graft.

PMID- 9236400
TI  - A word of caution regarding minimally invasive coronary artery bypass procedures.

PMID- 9236399
TI  - Supplement: proceedings of the VI International Symposium on Cardiac
      Bioprostheses.

PMID- 9236401
TI  - Mitral valve disease associated with use of anorexigenic medications.

PMID- 9236402
TI  - Postinfarct ventricular septal defects.

PMID- 9236403
TI  - Anatomic relationship of the left phrenic nerve to the internal mammary artery.

PMID- 9236404
TI  - Low-molecular-weight heparins for unstable angina. A better mousetrap?

PMID- 9236405
TI  - Surgically denervated cardiac transplant. Rewired or permanently unplugged?

PMID- 9236406
TI  - Defects in natural anticoagulant pathways as potential risk factors for
      myocardial infarction.

PMID- 9236407
TI  - Genetics of interventional cardiology. Old principles, new frontiers.

PMID- 9236408
TI  - Thrombomodulin gene mutations associated with myocardial infarction.
AB  - BACKGROUND: Thrombomodulin is an important receptor for thrombin on the
      endothelial cell surface of most blood vessels, including those of the heart.
      Thrombin-bound thrombomodulin activates protein C, which inhibits thrombin
      generation by degrading factors Va and VIIIa. The aim of this study was to
      analyze the 5' region of the thrombomodulin gene to determine whether mutations
      contribute a risk for myocardial infarction. METHODS AND RESULTS: We screened the
      promoter region of the thrombomodulin gene by single-stranded conformation
      polymorphism analysis in 104 patients with diagnosed myocardial infarction. Five
      mutations (three distinct) were identified (GG-9/-10AT, G-33A, and C-133A). The
      dinucleotide mutation GG-9/-10AT was identified in 3 individuals (2 heterozygous,
      1 homozygous). Only one of the three different mutations was identified in 104
      patient control subjects matched for age, sex, and race (G-33A in a single
      individual). All mutations identified were in close proximity to consensus
      sequences for transcription control elements within the thrombomodulin gene. In
      contrast, no difference was observed between patients and control subjects for
      the allelic frequency of a previously identified neutral polymorphism GCC/GTC
      coding for Ala/Val455, with 3 individuals homozygous for GTC (Val) in both
      groups. CONCLUSIONS: The findings suggest that mutations in the promoter region
      of the thrombomodulin gene may constitute a risk for arterial thrombosis.

PMID- 9236409
TI  - Morning hypercoagulability and hypofibrinolysis. Diurnal variations in
      circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin
      inhibitor complex.
AB  - BACKGROUND: Diurnal fluctuations of blood coagulation and fibrinolysis activity
      are thought to play a role in the observed circadian variation in the frequency
      of onset of acute cardiovascular events. In the present study, the diurnal
      variations in blood coagulation and fibrinolysis activity were investigated in 10
      young, healthy control subjects by use of specific molecular activation markers.
      METHODS AND RESULTS: The plasma levels of activated factor FVII (FVIIa), the
      active portion of the main coagulation activator, decreased during the day (8 AM:
      2.03 ng/mL, CI 1.16 to 2.88 ng/mL; 8 PM: 1.16 ng/mL, CI 0.81 to 1.5 ng/mL; P =
      .005), whereas FVII antigen did not change significantly. In parallel with the
      diurnal variations of FVIIa, we found a decrease of prothrombin fragment F1+2 (8
      AM: 0.97 nmol/L, CI 0.79 to 1.15 nmol/L; 8 PM: 0.78 nmol/L, CI 0.64 to 0.93
      nmol/L; P = .005), a molecular marker of intravasal thrombin generation. Evidence
      for a possible functional relevance of circulating FVIIa was found because this
      parameter was significantly correlated with prothrombin fragment F1+2 in 72
      fasting healthy individuals (r = .29, P = .011). Plasminogen activator inhibitor
      1 levels decreased (8 AM: 9.9 ng/mL, CI 7.7 to 12.1 ng/mL; 8 PM: 5.4 ng/mL, CI
      3.8 to 6.9 ng/mL; P < .005), whereas plasmin-plasmin inhibitor complex levels,
      representing the degree of intravascular plasmin generation, concomitantly
      increased (8 AM: 235 micrograms/L, CI 198 to 272 micrograms/L; 8 PM: 449
      micrograms/L, CI 391 to 507 micrograms/L; P = .008). CONCLUSIONS: Our data
      suggest that the diurnal changes in the plasma levels of activators and
      inhibitors of coagulation and fibrinolysis lead to corresponding changes in the
      activity state of these systems, leading to morning hypercoagulability and
      hypofibrinolysis.

PMID- 9236410
TI  - Chronic variant of myocarditis associated with hepatitis C virus infection.
AB  - BACKGROUND: Although molecular biological studies suggest a pathogenic link
      between enterovirus infection and dilated cardiomyopathy (DCM), the frequency of
      detection of enteroviral RNA is not consistently high in myocardial tissue from
      patients with DCM. A recent study has suggested that hepatitis C virus (HCV) may
      also be involved in the development of DCM. METHODS AND RESULTS: We performed
      genomic analysis for HCV in three patients with chronic active myocarditis. In
      all three patients, serum aminotransferase activities remained within normal
      ranges until the terminal stage of heart failure. At necropsy, all three livers
      showed evidence of tissue damage caused by chronic congestion, and one liver had
      evidence of chronic hepatitis. Routinely processed, paraffin-embedded tissue
      blocks of myocardium and liver were analyzed. Renal specimens were also analyzed
      to exclude the possibility of myocardial contamination with HCV material from the
      circulating blood. RNA extracted from the heart, liver, and kidney was subjected
      to strand-specific reverse transcription and amplified by semi-nested polymerase
      chain reaction. The target nucleotide sequence was a 178-bp fragment of the
      highly conserved 5'-noncoding region. Both positive- (genomic) and negative
      strand RNA (replicative intermediates) were present in myocardial and liver
      tissue samples from all three patients. However, negative-strand RNA was
      undetectable in renal tissue from one patient. CONCLUSIONS: These findings
      suggest that HCV replicated in myocardial tissue of these patients with
      myocarditis. Thus, HCV infection may contribute to the development of this
      unusual form of myocarditis.

PMID- 9236411
TI  - High glucose increases nitric oxide synthase expression and superoxide anion
      generation in human aortic endothelial cells.
AB  - BACKGROUND: Hyperglycemia is a primary cause of premature vascular disease.
      Endothelial cell dysfunction characterized by diminished endothelium-dependent
      relaxations is likely to be involved. Little is known about the molecular
      mechanisms of hyperglycemia-induced endothelial dysfunction. METHODS AND RESULTS:
      This study was designed to determine the effect of hyperglycemia on the L
      arginine/nitric oxide (NO) pathway. Expression of endothelial nitric oxide
      synthase (eNOS) mRNA and production of NO were studied in human aortic
      endothelial cells exposed to control levels (5.5 mmol/L) and high levels (22.2
      mmol/L) of glucose for 5 days. We examined the effect of glucose on NO release by
      measuring changes in nitrite (NO2-) levels by Griess reaction. Superoxide anion
      (O2-) production was also examined by the ferrocytochrome c assay. NOS mRNA and
      protein expression, which were evaluated by reverse transcription-polymerase
      chain reaction and Western blotting, were approximately twofold greater in
      endothelial cells exposed to high glucose. Elevated glucose levels increased NO2-
      production by only 40% but increased the release of O2- by more than threefold.
      CONCLUSIONS: The present study demonstrates that prolonged exposure to high
      glucose increases eNOS gene expression, protein expression, and NO release.
      However, upregulation of eNOS and NO release is associated with a marked
      concomitant increase of O2- production. These results provide the molecular basis
      for understanding how chronic exposure to elevated glucose leads to an imbalance
      between NO and O2-. This may explain impaired endothelial function and be
      important for diabetic vascular disease.

PMID- 9236413
TI  - Late surgical fenestration for complications after the Fontan operation.
AB  - BACKGROUND: Significant morbidity after Fontan operation results in either
      takedown, heart transplantation, or death. Initial creation of a fenestration
      results in less morbidity and mortality; however, the role of late creation of a
      fenestration in aiding patients manifesting morbidity after an initial
      nonfenestrated Fontan operation is unclear. METHODS AND RESULTS: We reviewed our
      experience with late creation of a surgical fenestration in 9 patients (5.2 +/-
      3.1 years old) exhibiting chronic effusions (n = 4) or protein-losing enteropathy
      (PLE) (n = 5) after lateral tunnel-type Fontan operation. Patients with effusions
      had creation via coronary punch of two or three 3-mm defects; patients with PLE
      had creation of a large, 5-mm defect. One child with effusions and multisystem
      organ failure before fenestration died 7 weeks after surgery secondary to low
      cardiac output; the other 3 had resolution of effusions within 4 to 6 weeks. Of
      the 5 with PLE, 3 had normalization of serum proteins and resolution of symptoms
      at 2 to 6 weeks. The 2 failures had arterial saturations > 89% after surgery.
      Follow-up was from 25 to 30 months. Spontaneous closure of defects occurred in
      all 3 with effusions. No return of symptoms was noted in 2; however, the third
      reaccumulated effusions and has undergone refenestration with a large defect. All
      3 patients with PLE have remained asymptomatic with patency of the fenestration
      (4 to 5 mm on echocardiography) and arterial saturation < or = 85% for > 2 years.
      CONCLUSIONS: Late surgical creation of fenestration results in resolution of
      morbidity after Fontan operation. Improvement is related to the degree of right
      to-left shunt created.

PMID- 9236412
TI  - Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning in human
      myocardium. Two paradoxes revisited.
AB  - BACKGROUND: Patients receiving oral hypoglycemic agents for diabetes mellitus are
      at increased risk of cardiovascular mortality. Oral hypoglycemic agents are
      inhibitors of the ATP-sensitive potassium (KATP) channel. Ischemic
      preconditioning is mediated by KATP channel activation. We therefore hypothesized
      that myocardium from patients taking long-term oral hypoglycemic agents would be
      resistant to the protection by ischemic preconditioning. METHODS AND RESULTS:
      Isolated human right atrial trabeculae were suspended in an organ bath at 37
      degrees C, with field stimulation at 1 Hz. Control trabeculae were then subjected
      to 45 minutes of simulated ischemia (hypoxic, glucose-free buffer with pacing at
      3 Hz) and 120 minutes of reperfusion. Ischemic preconditioned (IPC) trabeculae
      from patients without oral hypoglycemic therapy and from patients taking insulin
      (Ins+IPC) were given 5 minutes of simulated ischemia before this injury.
      Trabeculae (Oral Hypo+IPC) were obtained from patients taking long-term oral
      hypoglycemic agents and were also exposed to 5 minutes of simulated ischemia
      before this injury. Developed force (DF) was recorded. Recovery of DF relative to
      preischemic values was 28 +/- 4% in control trabeculae, whereas IPC trabeculae
      showed 52 +/- 5% recovery (P < .05 versus control). In patients receiving long
      term oral hypoglycemic agents (Oral Hypo+IPC), recovery of DF was 27 +/- 3%, but
      in trabeculae from insulin-treated patients (Ins+IPC), it was 45 +/- 6%.
      CONCLUSIONS: Human myocardium from patients without long-term exposure to oral
      hypoglycemic agents is functionally protected by preconditioning. Long-term oral
      hypoglycemic intake blocks the protection by preconditioning. These data suggest
      that ischemic preconditioning in human myocardium relies on KATP channels, and
      long-term inhibition of KATP channels with oral hypoglycemic agents may explain
      the excess cardiovascular mortality in these patients.

PMID- 9236414
TI  - Total, LDL, and HDL cholesterol decrease with age in older men and women. The
      Rancho Bernardo Study 1984-1994.
AB  - BACKGROUND: The purpose of the present study was to study the effects of age,
      weight change, and covariates on lipid and lipoprotein levels cross-sectionally
      and prospectively in an elderly population. METHODS AND RESULTS: A community
      based sample of 1041 men and 1303 women aged 50 to 93 years was studied cross
      sectionally in 1984 to 1987, with follow-up of 372 men and 545 women 8 years
      later. In the cross-sectional study, levels of total cholesterol (TC) and LDL
      cholesterol (LDL-C) decreased and levels of HDL cholesterol (HDLC) increased with
      age in men (all P < .001) but not in women. In the prospective study, TC, LDL-C,
      and HDL-C levels all decreased in both men and women, in all age groups (50 to 64
      years, 65 to 74 years, and > or = 75 years) and in all weight change groups (>
      2.5-kg loss, change within 2.5 kg, and > 2.5-kg gain) and in all waist girth
      change groups, for an overall decrement of approximately 1% per year. In multiple
      linear regression models, change in weight was the most important independent and
      consistent predictor of changes in TC, LDL-C, and HDL-C. Similar results were
      obtained in analyses excluding subjects taking lipid-lowering drugs or estrogen
      and in analyses adjusted for changes in cigarette smoking, alcohol intake,
      physical activity, medication use, and incident myocardial infarction, cancer, or
      diabetes. CONCLUSIONS: Cross-sectional decrements in TC and LDL-C with age in men
      are not explained by survivor bias because they are also observed prospectively.
      Although weight change was the most important explanatory variable, TC, LDL-C,
      and HDL-C levels also decreased in those who lost or gained weight. Age was not
      an independent predictor of change. Other prospective studies are recommended to
      better define the causes and consequences of cholesterol and lipoprotein changes
      in old age.

PMID- 9236415
TI  - Intermittent claudication. A risk profile from The Framingham Heart Study.
AB  - BACKGROUND: Intermittent claudication identifies persons at increased risk for
      death and disability. METHODS AND RESULTS: Using 38-year follow-up data for the
      original cohort in the Framingham Heart Study, we developed an intermittent
      claudication risk profile. Intermittent claudication occurred in a total of 381
      men and women. Age, sex, serum cholesterol, hypertension, cigarette smoking,
      diabetes, and coronary heart disease were associated with an increased risk for
      claudication and were included in the profile. A pooled logistic regression model
      was used to compute the probability of intermittent claudication for specified
      levels of risk factors. CONCLUSIONS: The intermittent claudication risk profile
      allows physicians to identify high-risk individuals during a routine office visit
      and can be used to educate patients about modifiable risk factors, particularly
      smoking and blood pressure. Improved compliance with risk factor modification
      strategies may result in a beneficial impact on survival.

PMID- 9236416
TI  - Prospective evaluation of dietary and other predictors of fatal stroke in
      Shanghai, China.
AB  - BACKGROUND: Although a number of risk factors for fatal stroke are well
      established in Western populations, this is less true for Asian countries, many
      of which have stroke mortality rates that are historically high. In a prospective
      study in Shanghai, China, we determined whether the same factors predict risk for
      fatal stroke as in the West. We also studied a number of potential dietary
      associations, particularly those with dietary antioxidants because these have
      been suggested to reduce atherogenesis. METHODS AND RESULTS: Between 1986 and
      1989, 18 244 men aged 45 to 64 years living in four geographically defined areas
      of Shanghai, China were recruited to participate in a prospective study of diet
      and cancer. All participants completed an in-person, structured interview and
      provided blood and urine samples. As of March 1994, fatal stroke accounted for
      245 of the 980 observed deaths. The most important risk factor for stroke
      mortality was a history of hypertension (multivariate relative risk, 4.5; 95%
      confidence interval, 3.3, 6.2). Cigarette smoking was not strongly associated
      with risk, and alcohol consumption increased risk only in the extreme categories
      of lifetime consumption. Educational level was strongly, inversely associated
      with fatal stroke, and this could not be explained by adjustment for any other
      risk factors. No macronutrient was associated with risk, including total energy,
      fat consumption, or any component of fat. There also were no significant inverse
      associations for stroke mortality with several micronutrients of interest,
      including vitamin C, carotene, vitamin E, riboflavin, or calcium. CONCLUSIONS:
      Our data demonstrate that hypertension is by far the most important contributor
      to stroke mortality in Shanghai and that among dietary factors, only alcohol
      consumption shows any evidence whatsoever of being a risk factor.

PMID- 9236417
TI  - D allele of the angiotensin I-converting enzyme is a major risk factor for
      restenosis after coronary stenting.
AB  - BACKGROUND: Although intracoronary stent implantation significantly reduces
      restenosis compared with balloon angioplasty, a minority of patients still
      develop restenosis predominantly due to neointimal hyperplasia. Experimental
      studies suggest that the renin-angiotensin system is involved in neointimal
      hyperplasia after arterial injury. In humans, the plasma and cellular levels of
      ACE are associated with an I/D genetic polymorphism in the ACE gene, DD patients
      having higher levels. METHODS AND RESULTS: We investigated a possible relation
      between the ACE I/D polymorphism and restenosis in 146 patients who underwent
      successful implantation of a Palmaz-Schatz stent and had 6-month follow-up
      angiography. The minimal lumen diameter (MLD) before and after the procedure did
      not differ significantly among the three groups of genotypes (DD, ID, and II). At
      follow-up, MLD had a significant inverse relationship to the number of D alleles
      present (DD, 1.65 +/- 0.71 mm; ID, 1.84 +/- 0.60 mm; II, 2.05 +/- 0.61 mm; P <
      .007). Late luminal loss during the follow-up period was significantly related to
      the number of D alleles (DD, 0.89 +/- 0.61 mm; ID, 0.60 +/- 0.52 mm; II, 0.40 +/-
      0.53 mm; P < .0001). The relative risk of restenosis (defined as a > 50% diameter
      stenosis at follow-up) approximated by the adjusted odds ratio was 2.00 per
      number of D alleles (95% confidence interval, 1.03 to 3.88, P < .04).
      CONCLUSIONS: The ACE I/D polymorphism influences the level of late luminal loss
      after coronary stent implantation. These results suggest that the renin
      angiotensin system may be implicated in the pathogenesis of restenosis after
      coronary stenting.

PMID- 9236418
TI  - Comparison of low-molecular-weight heparin with unfractionated heparin acutely
      and with placebo for 6 weeks in the management of unstable coronary artery
      disease. Fragmin in unstable coronary artery disease study (FRIC)
AB  - BACKGROUND: Low-molecular-weight heparin has a number of pharmacological and
      pharmacokinetic advantages over unfractionated heparin that make it potentially
      suitable, when used in combination with aspirin, for the treatment of unstable
      coronary artery disease. METHOD AND RESULTS: Patients with unstable angina or non
      Q-wave myocardial infarction (1482) were included in the study, which had two
      phases. In an open, acute phase (days 1 to 6), patients were assigned either
      twice-daily weight-adjusted subcutaneous injections of dalteparin (120 i.u./kg)
      or dose-adjusted intravenous infusion of unfractionated heparin. In the double
      blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously
      either dalteparin (7500 i.u. once daily) or placebo. During the first 6 days, the
      rate of death, myocardial infarction, or recurrence of angina was 7.6% in the
      unfractionated heparin-treated patients and 9.3% in the dalteparin-treated
      patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The
      corresponding rates in the two treatment groups for the composite end point of
      death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk,
      1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3%
      and 4.8% of patients in unfractionated heparin and dalteparin groups,
      respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45,
      the rate of death, myocardial infarction, or recurrence of angina was 12.3% in
      both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to
      1.38). The corresponding rates for death or myocardial infarction were 4.7% and
      4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures
      were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin
      groups, respectively. CONCLUSIONS: Our results add to previous evidence
      suggesting that the low-molecular-weight heparin dalteparin administered by twice
      daily subcutaneous injection may be an alternative to unfractionated heparin in
      the acute treatment of unstable angina or non-Q-wave myocardial infarction.
      Prolonged treatment with dalteparin at a lower once-daily dose in our study did
      not confer any additional benefit over aspirin (75 to 165 mg) alone.

PMID- 9236419
TI  - Diabetes mellitus, hypercholesterolemia, and hypertension but not vascular
      disease per se are associated with persistent platelet activation in vivo.
      Evidence derived from the study of peripheral arterial disease.
AB  - BACKGROUND: Previous studies relating increased thromboxane (TX) biosynthesis to
      cardiovascular risk factors do not answer the question whether platelet
      activation is merely a consequence of more prevalent atherosclerotic lesions or
      reflects the influence of metabolic and hemodynamic disturbances on platelet
      biochemistry and function. METHODS AND RESULTS: We examined 64 patients with
      large-vessel peripheral arterial disease and 64 age- and sex-matched control
      subjects. TXA2 biosynthesis was investigated in relation to cardiovascular risk
      factors by repeated measurements of the urinary excretion of its major enzymatic
      metabolite, 11-dehydro-TXB2, by radioimmunoassay. Urinary 11-dehydro-TXB2 was
      significantly (P = .0001) higher in patients with peripheral arterial disease (57
      +/- 26 ng/h) than in control subjects (26 +/- 7 ng/h). Seventy percent of
      patients had metabolite excretion > 2 SD above the normal mean. However, 11
      dehydro-TXB2 excretion was enhanced only in association with cardiovascular risk
      factors. Multivariate analysis showed that diabetes, hypercholesterolemia, and
      hypertension were independently related to 11-dehydro-TXB2 excretion. During a
      median follow-up of 48 months, 8 patients experienced major vascular events.
      These patients had significantly (P = .001) higher 11-dehydro-TXB2 excretion at
      baseline than patients who remained event free. CONCLUSIONS: The occurrence of
      large-vessel peripheral arterial disease per se is not a trigger of platelet
      activation in vivo. Rather, the rate of TXA2 biosynthesis appears to reflect the
      influence of coexisting disorders such as diabetes mellitus,
      hypercholesterolemia, and hypertension on platelet biochemistry and function.
      Enhanced TXA2 biosynthesis may represent a common link between such diverse risk
      factors and the thrombotic complications of peripheral arterial disease.

PMID- 9236420
TI  - First chronic platelet glycoprotein IIb/IIIa integrin blockade. A randomized,
      placebo-controlled pilot study of xemilofiban in unstable angina with
      percutaneous coronary interventions.
AB  - BACKGROUND: Clinical studies have demonstrated the efficacy of intravenous
      administration of agents that block platelet glycoprotein IIb/IIIa receptors in
      the setting of percutaneous coronary revascularization. Although the optimal
      duration of treatment has not been determined, more prolonged receptor blockade
      has been associated with increased efficacy. Orally active glycoprotein IIb/IIIa
      receptor antagonists may be advantageous and required for chronic therapy.
      METHODS AND RESULTS: Thirty patients with unstable angina who were undergoing
      percutaneous coronary interventions were randomized to placebo or Xemilofiban 35
      mg orally before and 20 to 25 mg TID for 30 days after angioplasty. Bleeding
      events, platelet aggregation, and pharmacokinetic and hematologic parameters were
      assessed during hospitalization and at 2 and 4 weeks after drug initiation.
      Xemilofiban produced a rapid, sustained, marked inhibition of platelet
      aggregation. ADP-induced platelet aggregation at 2 hours after the initial dose
      at 2 and 4 weeks was 15%, 8%, and 11% in the Xemilofiban group compared with 80%,
      68%, and 69% in the placebo group. Among 20 patients randomized to Xemilofiban
      there was 1 death after emergency coronary bypass surgery complicated by severe
      bleeding diathesis, and 3 patients had major bleeding events. Patients on
      Xemilofiban for 30 days reported episodes of mild mucocutaneous bleeding.
      CONCLUSIONS: Xemilofiban, an orally active glycoprotein IIb/ IIIa receptor
      inhibitor, produced rapid, sustained, extensive inhibition of platelet
      aggregation for a period of up to 30 days. At the dose initially tested, however,
      acute major bleeding and mucocutaneous bleeding during chronic administration
      were encountered.

PMID- 9236421
TI  - Redifferentiation of smooth muscle cells after coronary angioplasty determined
      via myosin heavy chain expression.
AB  - BACKGROUND: The pathophysiology of phenotypic modulation of smooth muscle cells
      (SMCs) involved in restenosis after angioplasty is not well understood. Smooth
      muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers
      for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs.
      SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated
      in immature or activated SMC. METHODS AND RESULTS: To determine SMC phenotypes in
      neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA),
      we performed immunohistochemistry on human coronary arteries with antibodies
      against alpha-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six
      autopsied patients and from atherectomy specimens from 16 patients who had
      undergone PTCA. Medial SMCs were positive for alpha-actin, SM1, and SM2.
      Expression of SM1 and SM2 in the neointima varied with the time after
      intervention, whereas alpha-actin was constitutively expressed in all cases
      studied. Neointimal cells at 16 and 20 days after PTCA contained alpha-actin but
      little or no SM1 or SM2, indicating that these cells modulated their phenotype to
      the immature state. Neointimal SMCs recovered SM MHC expression, first SM1 and
      then SM2, by 6 months after PTCA. Increased expression of SMemb was found in the
      neointima but without apparent relationship to the time after PTCA. CONCLUSIONS:
      Neointimal SMCs show features of an undifferentiated state, indicated by altered
      expression of SM MHC, and undergo redifferentiation in a time-dependent manner.
      The expression of SM MHC isoforms provides insight into the biology of healing
      after angioplasty and furnishes useful tools for the understanding of the roles
      of differentiation and phenotypic modulation of SMCs in human vascular lesions.

PMID- 9236422
TI  - Randomized comparison of angioplasty of complex coronary lesions at a single
      center. Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison
      (ERBAC) Study.
AB  - BACKGROUND: The purpose of this study was to test whether coronary
      revascularization with ablation of either excimer laser or rotational atherectomy
      can improve the initial angiographic and clinical outcomes compared with
      dilatation (balloon angioplasty) alone. METHODS AND RESULTS: At a single center,
      a total of 685 patients with symptomatic coronary disease warranting elective
      percutaneous revascularization for a complex lesion were randomly assigned to
      balloon angioplasty (n = 222), excimer laser angioplasty (n = 232), or rotational
      atherectomy (n = 231). The primary end point was procedural success (diameter
      stenosis < 50%, absence of death, Q-wave myocardial infarction, or coronary
      artery bypass surgery). The patients who underwent rotational atherectomy had a
      higher rate of procedural success than those who underwent excimer laser
      angioplasty or conventional balloon angioplasty (89% versus 77% and 80%, P =
      .0019), but no difference was observed in major in-hospital complications (3.2%
      versus 4.3% versus 3.1%, P = .71). At the 6-month follow-up, revascularization of
      the original target lesion was performed more frequently in the rotational
      atherectomy group (42.4%) and the excimer laser group (46.0%) than in the
      angioplasty group (31.9%, P = .013). CONCLUSIONS: Procedural success of
      rotational atherectomy is superior to laser angioplasty and balloon angioplasty;
      however, it does not result in better late outcomes. The role of plaque debulking
      before balloon dilatation in percutaneous coronary revascularization remains to
      be fully defined.

PMID- 9236423
TI  - Determination of human coronary artery composition by Raman spectroscopy.
AB  - BACKGROUND: We present a method for in situ chemical analysis of human coronary
      artery using near-infrared Raman spectroscopy. It is rapid and accurate and does
      not require tissue removal; small volumes, approximately 1 mm3, can be sampled.
      This methodology is likely to be useful as a tool for intravascular diagnosis of
      artery disease. METHODS AND RESULTS: Human coronary artery segments were obtained
      from nine explanted recipient hearts within 1 hour of heart transplantation.
      Minces from one or more segments were obtained through grinding in a mortar and
      pestle containing liquid nitrogen. Artery segments and minces were excited with
      830 nm near-infrared light, and Raman spectra were collected with a specially
      designed spectrometer. A model was developed to analyze the spectra and quantify
      the amounts of cholesterol, cholesterol esters, triglycerides and phospholipids,
      and calcium salts present. The model provided excellent fits to spectra from the
      artery segments, indicating its applicability to intact tissue. In addition, the
      minces were assayed chemically for lipid and calcium salt content, and the
      results were compared. The relative weights obtained using the Raman technique
      agreed with those of the standard assays within a few percentage points.
      CONCLUSIONS: The chemical composition of coronary artery can be quantified
      accurately with Raman spectroscopy. This opens the possibility of using
      histochemical analysis to predict acute events such as plaque rupture, to follow
      the progression of disease, and to select appropriate therapeutic interventions.

PMID- 9236424
TI  - Pharmacological modulation of the human collateral vascular resistance in acute
      and chronic coronary occlusion assessed by intracoronary blood flow velocity
      analysis in an angioplasty model.
AB  - BACKGROUND: The pharmacological responsiveness of the coronary collateral
      circulation in humans has been studied only by indirect means. METHODS AND
      RESULTS: Patients with one-vessel disease and recruitable (n = 14) or
      spontaneously visible (n = 24) collateral vessels were studied during coronary
      angioplasty. Collateral flow in the recipient coronary artery was determined with
      a 0.014-in Doppler guide wire during balloon coronary occlusion and expressed as
      the diastolic blood flow velocity integral (dVi). Collateral blood flow velocity,
      mean aortic pressure (Pao), and coronary wedge pressure (Pw) were used to
      calculate the collateral vascular resistance index: Rcoll = (Pao-Pw)/ dVi (mm
      Hg/cm) and the peripheral vascular resistance index of the recipient coronary
      artery: R4 = Pw/dVi (mm Hg/cm). Adenosine (12 to 18 micrograms) and nitroglycerin
      (0.2 mg) were injected as a bolus in the donor coronary artery during subsequent
      balloon inflations to assess their effect on these hemodynamic variables. The
      administration of adenosine or nitroglycerin in patients with recruitable
      collateral vessels did not induce a change in dVi and Pw/Pao ratio. In patients
      with spontaneously visible collateral vessels, dVi increased from 8.0 +/- 4.5 to
      10.8 +/- 8.0 cm (P = .01) after adenosine and from 7.4 +/- 4.5 to 10.3 +/- 6.9 cm
      (P = .003) after nitroglycerin. The Pw/Pao ratio remained unchanged after
      adenosine and nitroglycerin. Rcoll decreased from 10.3 +/- 9.5 to 8.6 +/- 8.5 mm
      Hg/cm (P = .01) after adenosine and from 11.6 +/- 10.4 to 8.3 +/- 8.9 mm Hg/cm (P
      < .001) after nitroglycerin. R4 decreased from 7.7 +/- 5.5 to 5.9 +/- 5.1 mm
      Hg/cm (P < .001) after adenosine and from 8.4 +/- 6.6 to 7.1 +/- 7.2 mm Hg/cm (P
      = .01) after nitroglycerin. CONCLUSIONS: Coronary collateral blood flow can be
      increased with adenosine and nitroglycerin in patients with one-vessel disease
      and spontaneously visible collateral vessels, which is in contrast to patients
      with recruitable collateral vessels. This effect is the result of a reduction in
      the collateral vascular resistance and peripheral vascular resistance of the
      recipient coronary artery.

PMID- 9236425
TI  - End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute
      myocardial infarction is a strong predictor of early and late mortality. The
      Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries
      (GUSTO)-I Angiographic Investigators.
AB  - BACKGROUND: Left ventricular remodeling is an important sequela of myocardial
      infarction (MI). Although remodeling occurs soon after MI, the effect of early
      left ventricular dilatation on outcome is not established and may be useful for
      early risk stratification. We assessed whether end-systolic volume index (ESVI)
      at 90 to 180 minutes into thrombolytic therapy for MI is associated with adverse
      outcomes. METHODS AND RESULTS: In the Global Utilization of Streptokinase and t
      PA for Occluded Coronary Arteries (GUSTO)-I study, 41021 patients with evolving
      MI received one of four thrombolytic regimens. At 90 or 180 minutes into
      reperfusion therapy, 1300 patients underwent left ventriculography. ESVI was
      measured and correlated with adverse outcomes: 30-day and 1-year mortality and in
      hospital congestive heart failure, shock, and reinfarction. Clinical variables
      were also tested in a stepwise logistic regression analysis to determine
      predictors of left ventricular dilatation. ESVI was directly related to all
      adverse outcomes with univariate analysis. ESVI of > or = 40 mL/m2 was
      independently associated with mortality (adjusted odds ratio [95% confidence
      interval]: 30-day, 3.4 [2.0 to 5.9]; 1-year, 4:1 [2.6 to 6.2], both P < .001).
      Male sex, prior angina or MI, weight of < 70 kg, heart rate of > or = 80 bpm,
      systolic blood pressure of < 110 mm.Hg, and anterior infarction were independent
      predictors of an ESVI of > or = 40 mL/m2. CONCLUSIONS: Left ventricular ESVI
      early into reperfusion therapy for MI strongly predicts adverse outcomes,
      including early and late mortality. The study establishes the role of very early
      left ventricular dilatation on outcome in MI and may be useful in identifying
      high-risk patients who might benefit from aggressive treatment, including the
      early use of ACE inhibitors.

PMID- 9236426
TI  - Impact of an aggressive invasive catheterization and revascularization strategy
      on mortality in patients with cardiogenic shock in the Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
      (GUSTO-I) trial. An observational study.
AB  - BACKGROUND: Although retrospective analyses have revealed an association between
      survival and coronary angiography and angioplasty in patients with acute
      myocardial infarction complicated by cardiogenic shock, the degree to which bias
      in the selection of patients to undergo these procedures contributes to this
      observation remains unclear. METHODS AND RESULTS: We studied 2200 patients in the
      Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries (GUSTO-I) trial with acute myocardial infarction complicated by
      cardiogenic shock (systolic blood pressure < 90 mm Hg for > or = 1 hour) who
      survived > or = 1 hour after the onset of shock to determine the influence of an
      aggressive strategy of early angiography (within 24 hours of shock onset) and
      coronary angioplasty or bypass surgery, if appropriate, on survival.
      Revascularization was not protocol mandated but was selected by the attending
      physicians. Shock was present on admission in 11% and developed after admission
      in 89% of shock patients. The 30-day mortality was 38% in the 406 patients who
      underwent early angiography and were referred within 24 hours for angioplasty (n
      = 175), bypass surgery (n = 36), angioplasty and bypass surgery (n = 22), or
      neither (late or no revascularization, n = 173) compared with 62% in the 1794
      patients who did not (P = .0001). However, there were important differences in
      the baseline characteristics of the two groups, including younger age (63 versus
      68 years, P = .0001), less prior infarction (19% versus 27%, P = .001), and a
      shorter time to thrombolytic therapy (2.9 versus 3.2 hours, P = .0001) in
      patients treated with an aggressive strategy. Using multivariate logistic
      regression analysis to adjust for differences in baseline characteristics, an
      aggressive strategy was independently associated with reduced 30-day mortality
      (odds ratio, 0.43 [confidence interval, 0.34 to 0.54], P = .0001). CONCLUSIONS:
      An aggressive strategy of early angiography (and revascularization when
      appropriate) is associated with a reduction in mortality in patients with acute
      myocardial infarction and cardiogenic shock who receive thrombolytic therapy.

PMID- 9236427
TI  - Coronary stenting after rotational atherectomy in calcified and complex lesions.
      Angiographic and clinical follow-up results.
AB  - BACKGROUND: Treatment of calcified (in contrast to simple) lesions with PTCA has
      been associated with a lower success rate and more procedural complications.
      Rotablation can improve acute results, but the high restenosis rate remains a
      problem. The purpose of this study was to evaluate the clinical and angiographic
      outcome of patients with complex and calcified lesions treated with a combination
      of rotablation and stenting. METHODS AND RESULTS: Seventy-five consecutive
      patients with 106 lesions had rotablation prior to coronary stenting.
      Intravascular ultrasound-guided stenting was used without subsequent
      anticoagulation in 93% of patients. Procedural success was achieved in 93.4% of
      lesions. Acute stent thrombosis occurred in two lesions (1.9%), and subacute
      stent thrombosis in one lesion (0.9%). Angiographic follow-up was performed in
      82.5% of lesions at 4.6 +/- 1.9 months with an angiographic restenosis rate of
      22.5%. Clinical follow-up was performed in all patients at 6.4 +/- 3 months;
      target lesion revascularization was needed in 18% of lesions; Q-wave myocardial
      infarction occurred in 1.3%, coronary bypass surgery in 4.0%, and death in 1.3%.
      CONCLUSIONS: Optimal coronary stenting after rotablation in calcified and complex
      lesions can be performed with a high success rate, an acceptable rate of
      procedural complications, and a low rate of stent thrombosis. This approach was
      associated with a low incidence of angiographic restenosis compared with results
      usually obtained with other interventional strategies in calcified and complex
      lesion subsets.

PMID- 9236428
TI  - Cardiac imaging for risk stratification with dobutamine-atropine stress testing
      in patients with chest pain. Echocardiography, perfusion scintigraphy, or both?
AB  - BACKGROUND: Pharmacological stress echocardiography and myocardial perfusion
      scintigraphy are used frequently for risk stratification in patients with
      suspected myocardial ischemia. However, their relative prognostic strength has
      never been explored. METHODS AND RESULTS: Two hundred twenty consecutive patients
      with chest pain (mean age, 60 +/- 12 years; 124 men, 115 with previous myocardial
      infarction) were studied with dobutamine-atropine stress echocardiography (ECHO)
      and simultaneous 99mTc sestamibi single photon emission computed tomography
      imaging (MIBI). Ischemia was defined as deterioration in left ventricular wall
      motion and reversible perfusion defects, respectively. ECHO was positive for
      ischemia in 76 and MIBI in 91 patients (agreement, 77%; kappa = .51). During
      follow-up of 31 +/- 15 months, 24 patients had hard cardiac events (nonfatal
      myocardial infarction or cardiac death). By univariate analysis, age, history of
      congestive heart failure, and any abnormality or ischemia on ECHO or MIBI were
      associated with cardiac events. Multivariate analysis revealed that age, abnormal
      ECHO (odds ratio [OR], 18.9; 95% CI, 2.5 to 146.0) or MIBI (OR, 12.8; 95% CI, 1.7
      to 98.3), and ischemia on ECHO (OR, 4.0; 95% CI, 1.6 to 9.9) or MIBI (OR, 3.0;
      95% CI, 1.2 to 7.4) had independent predictive values. When ECHO was used as a
      first option, the addition of MIBI to all nonischemic ECHO studies decreased the
      OR from 4.0 (95% CI, 1.6 to 9.9) to 3.8 (95% CI, 1.4 to 10.2). Addition of MIBI
      confined to nonischemic ECHO studies in which target heart rate was not attained
      (nondiagnostic studies) increased the OR to a maximal 5.7 (95% CI, 2.2 to 15.0).
      In contrast, the addition of ECHO to nondiagnostic MIBI studies was not useful.
      CONCLUSIONS: Dobutamine-atropine ECHO and MIBI provide comparable prognostic
      information. The addition of MIBI to ECHO may be useful in patients with
      nondiagnostic ECHO studies.

PMID- 9236429
TI  - Intracoronary angiotensin II potentiates coronary sympathetic vasoconstriction in
      humans.
AB  - BACKGROUND: In humans with coronary artery disease, ACE inhibition attenuates
      coronary sympathetic vasoconstriction. Whether this is due to removal of
      angiotensin (Ang) II production or to a reduced bradykinin breakdown, however, is
      unknown. METHODS AND RESULTS: In eight normotensive patients with angiographic
      evidence of mild left coronary artery lesions (< or = 50%), mean arterial
      pressure (MAP, intra-arterial catheter), heart rate (HR, ECG lead), coronary
      sinus blood flow (CBF, thermodilution method), and coronary vascular resistance
      (CVR, ratio between MAP and CBF) were measured before and during a 15-minute left
      intracoronary infusion of Ang II at a dose that had no direct coronary or
      systemic vasomotor effects. The same measurements were made before and during a
      15-minute infusion of saline. A 2-minute cold pressor test (CPT) and a 45-second
      diving were performed at the end of either infusion period. These maneuvers were
      used because their coronary vasomotor effects are abolished by phentolamine and
      thus depend on sympathetic activation. During saline infusion, both CPT and
      diving caused a marked increase in MAP. HR increased with CPT and fell with
      diving. CBF increased in parallel to the MAP increase, with little change in CVR.
      The MAP and HR responses were similar during Ang II infusion, which, however,
      caused either no change or a reduction in CBF with a consequent marked increase
      in CVR with both CPT and diving. In four additional patients, the diameter of the
      stenotic vessels remained unchanged during the CPT performed under saline and Ang
      II infusion. CONCLUSIONS: Ang II markedly enhances sympathetic influences on
      coronary circulation in humans, presumably by acting at the arteriolar level.
      This may explain the blunting effect of ACE inhibition on sympathetic coronary
      vasoconstriction in patients with coronary artery disease.

PMID- 9236430
TI  - Site-specific intracoronary heparin delivery in humans after balloon angioplasty.
      A radioisotopic assessment of regional pharmacokinetics.
AB  - BACKGROUND: Demonstration and quantification of site-specific intracoronary
      administration of compounds has been confined thus far to the experimental animal
      laboratory. The aim of this study was to describe a scintigraphic method to
      demonstrate site-specific intracoronary drug delivery in humans. The methods
      allow on-line visualization and off-line quantification of site-specifically
      infused gamma-emitting compounds. METHODS AND RESULTS: In 12 patients after
      balloon angioplasty, 99mTc-labeled heparin was administered at the site of
      dilatation by use of a coil balloon. Both the infusion period and the washout
      period after the end of infusion were monitored with a gamma-camera. A curve of
      counts per pixel as a function of time was derived that showed an accumulation
      phase during infusion followed by washout phase after the end of infusion. Both
      phases were fitted by regression analysis and showed a linear accumulation
      pattern and a biexponential washout pattern. After correction for background
      counts, 99mTc decay, and body attenuation, peak heparin amount and regional
      bioavailability were calculated. Peak amount was defined as the initial point of
      the slow washout component of the biexponential curve (elimination component),
      and regional bioavailability was defined as the area under the curve of
      accumulation and washout phase. Half-life and retention time, define as seven
      half-lives, were obtained by use of the elimination component after correction
      for 99mTc decay. Mean peak delivered amount was 45 +/- 44 IU (236 +/- 228
      micrograms), corresponding to an efficiency of delivery ranging from 1% to 8% of
      the totally infused dose. Total regionally bioavailable heparin reached 244 +/-
      194 IU.h (1.28 +/- 1.01 mg.h). Retention time varied from 12 to 90 hours (mean,
      50:33 +/- 22:50 hours:minutes). CONCLUSIONS: Site-specific intracoronary heparin
      delivery after angioplasty by means of the coil balloon was demonstrated in
      humans, and regional pharmacokinetics was quantified by use of a radioisotopic
      technique.

PMID- 9236431
TI  - Association of an acute reduction in lipoprotein(a) with coronary artery
      restenosis after percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)], which structurally resembles-tissue-type
      plasminogen, is reported to be associated with coronary atherosclerosis. We
      examined whether the acute change in Lp(a) by percutaneous transluminal coronary
      angioplasty (PTCA) is related to restenosis after PTCA. METHODS AND RESULTS: We
      measured serum Lp(a) and other lipid parameters (triglycerides and total, LDL,
      and HDL cholesterol) before and 1 day after PTCA in 143 procedures and 3 days
      after and 4 months after PTCA in 62 procedures. Quantitative coronary angiography
      was performed, and restenosis was defined according to three criteria: (1)
      clinical recurrence of ischemic symptoms, (2) a final stenosis > 50%, and (3) an
      absolute decrease in minimal lumen diameter > 1/2 of the acute gain in the
      dilated segment. Restenosis was recognized in 25.9%, 35.7%, and 38.5% of the
      cases 4 months after PTCA for each criterion, respectively. Although triglyceride
      and LDL, HDL, and total cholesterol levels were similar in the restenosis and no
      restenosis groups before PTCA, Lp(a) was significantly higher in the restenosis
      group. We found a significant reduction in Lp(a) in the restenosis but not the no
      restenosis group 1 day after PTCA. At 3 days after and 4 months after PTCA, Lp(a)
      was similar in the two groups. A multivariate-analysis revealed that the absolute
      change in Lp(a) (before versus 1 day after PTCA) to be the sole significant
      predictor of restenosis among the clinical, angiographic, and plasma lipid
      parameters examined. CONCLUSIONS: Lp(a) levels were significantly higher in the
      restenosis group, and they fell significantly after PTCA in the restenosis group.

PMID- 9236432
TI  - Perindopril chronically inhibits angiotensin-converting enzyme in both the
      endothelium and adventitia of the internal mammary artery in patients with
      ischemic heart disease.
AB  - BACKGROUND: ACE inhibitors are widely used in treating hypertension and heart
      failure, but the sites and mechanisms of ACE inhibition in human blood vessels
      are not understood. The present study was undertaken to assess the sites and
      extent of in vivo inhibition of ACE by long-term perindopril treatment in
      different layers of the internal mammary artery in patients with ischemic heart
      disease. METHODS AND RESULTS: Sixteen patients with ischemic heart disease were
      treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n =
      9) or without the inhibitor as control subjects (n = 7). The segments of the
      internal mammary artery were collected for measurement of vascular free and total
      ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients
      treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin
      (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was
      similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P
      < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was
      markedly decreased by perindopril in parallel in the endothelium (P < .001) and
      adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE
      in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and
      mean arterial pressure correlated significantly with free ACE in the endothelium
      (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to
      Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A
      binding revealed a marked inhibition of ACE by perindopril in both layers of the
      vascular wall. CONCLUSIONS: The present demonstrates that long-term
      administration of perindopril potently inhibits both endothelial and adventitial
      ACE to a comparable degree in the human internal mammary artery. These results
      indicate that perindopril effectively penetrates the vascular wall to inhibit ACE
      in the adventitia, thus providing evidence that perindopril may be beneficial in
      inhibiting both circulating Ang II and its local formation in the vascular wall.

PMID- 9236433
TI  - Beneficial effects of intravenous and oral carvedilol treatment in acute
      myocardial infarction. A placebo-controlled, randomized trial.
AB  - BACKGROUND: Evidence of efficacy and safety of beta-blockers after thrombolysis
      for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as
      carvedilol have not been tested in this setting. METHODS AND RESULTS: This study
      investigated the effects of acute (intravenous) and long-term (6 months, oral)
      treatment with carvedilol versus placebo in 151 consecutive patients with AMI.
      Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were
      performed before hospital discharge and at 3 and 6 months. All patients were
      followed up and cardiovascular events recorded. The Cox proportional hazards
      model was used to compare time from randomization with the occurrence of a
      cardiovascular event, and Kaplan-Meier survival curves were calculated.
      Carvedilol was found to be safe, and it significantly reduced cardiac events
      compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four
      patients had heart failure at study entry; 34 received carvedilol. There were no
      adverse effects of carvedilol therapy and no excess events in this subgroup.
      Carvedilol produced significant reductions in heart rate (P < .0001), blood
      pressure (P < .005) at rest, and rate-pressure product at peak exercise (P <
      .003), but exercise capacity was unchanged. Left ventricular ejection fraction
      was not altered significantly by carvedilol, but stroke volume was higher at pre
      hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of
      the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a
      subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on
      carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling.
      CONCLUSIONS: Carvedilol was well tolerated and safe to use in patients
      immediately after AMI, including those with heart failure, and significantly
      improved outcome.

PMID- 9236434
TI  - Effects of RheothRx on mortality, morbidity, left ventricular function, and
      infarct size in patients with acute myocardial infarction. Collaborative
      Organization for RheothRx Evaluation (CORE).
AB  - BACKGROUND: Previous studies suggested that RheothRx (poloxamer 188) reduces
      infarct size and improves left ventricular (LV) function in acute myocardial
      infarction (AMI). We therefore evaluated the effects of various doses of RheothRx
      in 2948 patients presenting with AMI. METHODS AND RESULTS: Patients were
      randomized to a control group (n = 963) or to receive RheothRx. Patients
      receiving RheothRx were allocated to receive a 1-hour bolus only (regimen A, n =
      844), an additional 11-hour infusion at a low dose (target serum concentration of
      0.5 mg/mL) (regimen Y, n = 490), or an additional 23-hour infusion at a low dose
      (regimen B, n = 483). Three higher doses (1-hour bolus+low-dose infusion for 47
      hours, 1-hour bolus+high dose, target serum concentration of 1.0 mg/ml for 24
      hours, or 1-hour bolus+high dose for 48 hours) were discontinued because of high
      rates of renal dysfunction (8.8%). Renal dysfunction was also observed at lower
      doses (regimen A, 3.1%; Y, 2.7%; and B, 4.1%) compared with the control patients
      (1.0%). There was no significant difference in the composite outcome of death,
      cardiogenic shock, or reinfarction at 35 days (all RheothRx, 13.6%; control,
      12.7%). There was a higher incidence of sinus tachycardia (24.7% versus 21.6%, P
      = .02), atrial flutter (3.0% versus 1.3%, P = .019), atrial fibrillation (10.2%
      versus 7.3%, P = .082), pericarditis (6.6% versus 4.7%, P = .055), and clinical
      (21.9% versus 17.9%, P = .005) and radiological (15.3% versus 12.3%, P = .12)
      evidence of heart failure. This was associated with a lower LV ejection fraction
      (n = 1053) in treated patients (by = -0.02, P = .026), but there was little
      difference (P = .34) in infarct size (n = 1088). CONCLUSIONS: In this study of
      nearly 3000 patients, RheothRx had no effect on mortality, reinfarction, or
      cardiogenic shock and an adverse effect on renal function, LV ejection fraction,
      and various clinical manifestations of LV dysfunction or heart failure.

PMID- 9236435
TI  - Risk stratification after myocardial infarction using signal-averaged
      electrocardiographic criteria adjusted for sex, age, and myocardial infarction
      location.
AB  - BACKGROUND: The objectives were to investigate the factors influencing signal
      averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and
      to develop criteria for predicting arrhythmic events (AEs) that account for these
      factors. METHODS AND RESULTS: SAECGs were recorded 5 to 15 days after MI in 2461
      patients without bundle-branch block. The duration (QRSd), terminal potential
      (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During
      follow-up (17 +/- 8 months), AEs (arrhythmic death; ventricular tachycardia, VT;
      ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating
      characteristic curves showed that QRSd discriminated patients with all types of
      AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also
      discriminated AE patients. Sex, age, and MI location significantly affected the
      SAECG; survivors without VT or VF were divided into subgroups (2 sex x 4 age x 2
      MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs
      with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall
      sensitivity and specificity but with less uniform values for each subgroup. A Cox
      model was constructed by use of multiple prognostic indicators, and in rank
      order, QRSd, previous MI, and Killip class were predictive of AEs. CONCLUSIONS:
      SAECG adjustments for sex, age, and MI location did not improve sensitivity and
      specificity but produced a more uniform predictive performance. The proposed
      criteria are based only on QRSd, because late potentials (VRMS and LAS) did not
      discriminate patients with sudden death. Duration of high-level activity during
      QRS (QRSd-LAS) can predict AEs, suggesting that the arrhythmogenic substate
      involves a large mass of myocardium.

PMID- 9236436
TI  - Diagnostic value of electrocardiography and echocardiography for familial
      hypertrophic cardiomyopathy in a genotyped adult population.
AB  - BACKGROUND: The diagnostic value of ECG and echocardiography for familial
      hypertrophic cardiomyopathy (FHC) has not been reassessed since the development
      of molecular genetics. The aim of the study was to evaluate it in adults, with
      the genetic status used as the criterion of reference. METHODS AND RESULTS: Ten
      families with previously identified mutations were studied (9 mutations in 3
      genes). ECG and echocardiography were analyzed in 155 adults, of whom 77 were
      genetically affected and 78 unaffected. The major diagnostic criteria were, for
      echocardiography, a left ventricular wall thickness > 13 mm and, for ECG,
      abnormal Q waves, left ventricular hypertrophy, and marked ST-T changes. Minor
      ECG and echographic abnormalities were also analyzed. (1) Sensitivity and
      specificity of major criteria were 61% and 97% for ECG and 62% and 100% for
      echocardiography. (2) Sensitivity but not specificity was age related (from 50%
      at < 30 years to 94% at > 50 years old, P < .01) and sex related (83% in men
      versus 57% in women, P = .01). (3) Sensitivity was improved by the addition of
      minor criteria and by the association of ECG and echocardiography. The negative
      predictive value was therefore very good (95%) at > 30 years of age. (4) Healthy
      carriers without any ECG or echocardiographic abnormality represented 17% of
      genetically affected adults. CONCLUSIONS: ECG and echocardiography have similar
      diagnostic values for FHC in adults, with an excellent specificity and a lower
      sensitivity. The association of the two techniques allows a better evaluation of
      the risk of being genetically affected in families with hypertrophic
      cardiomyopathy.

PMID- 9236437
TI  - Prorenin, renin, angiotensinogen, and angiotensin-converting enzyme in normal and
      failing human hearts. Evidence for renin binding.
AB  - BACKGROUND: A local renin-angiotensin system in the heart is often invoked to
      explain the beneficial effects of ACE inhibitors in heart failure. The heart,
      however, produces little or no renin under normal conditions. METHODS AND
      RESULTS: We compared the cardiac tissue levels of renin-angiotensin system
      components in 10 potential heart donors who died of noncardiac disorders and 10
      subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation.
      Cardiac levels of renin and prorenin in DCM patients were higher than in the
      donors. The cardiac and plasma levels of renin in DCM were positively correlated,
      and extrapolation of the regression line to normal plasma levels yielded a tissue
      level close to that measured in the donor hearts. The cardiac tissue-to-plasma
      concentration (T/P) ratios for renin and prorenin were threefold the ratio for
      albumin, which indicates that the tissue levels were too high to be accounted for
      by admixture with blood and diffusion into the interstitial fluid. Cell membranes
      from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio
      for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac
      angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio
      was half that for albumin, which is compatible with substrate consumption by
      cardiac renin. CONCLUSIONS: These data in patients with heart failure support the
      concept of local angiotensin production in the heart by renin that is taken up
      from the circulation. Membrane binding may be part of the uptake process.

PMID- 9236438
TI  - Survival and risk factors for death after cardiac transplantation in infants. A
      multi-institutional study. The Pediatric Heart Transplant Study.
AB  - BACKGROUND: Despite the increasing application of cardiac transplantation in
      infants, reported survival rates vary, and risk factors for death are poorly
      understood. METHODS AND RESULTS: To examine early survival and risk factors for
      death in infants (< 1 year of age) undergoing cardiac transplantation, 141
      infants (36 < 1 months of age) underwent primary cardiac transplantation between
      January 1, 1993, and January 1, 1995, at 23 centers in the Pediatric Heart
      Transplant Study (PHTS). Diagnoses were hypoplastic left heart syndrome (66%),
      other congenital heart disease (17%), cardiomyopathy (14%), and other (3%).
      Actuarial survival after cardiac transplantation was 84% at 1 month, 70% at 1
      year, and 69% at 2 years, with the greatest hazard for death within the first 3
      months. The principal cause of death was early graft failure in 20 patients (52%
      of deaths), infection in 10 (26% of deaths), and rejection in 4 (10%). On the
      basis of multivariate analysis, risk factors for early mortality were history of
      previous sternotomy (P = .0003), nonidentical blood type donor (P = .01),
      recipient non-blood group A (P = .02), and donor cause of death other than closed
      head trauma (P = .04). Diagnosis at listing, waiting time (mean, 1.3 months),
      graft ischemic time (mean, 228 minutes; range, 68 to 479 minutes), and recipient
      ventilatory or inotropic support at listing were not predictive for mortality
      after transplant. CONCLUSIONS: The higher mortality rate observed with infant
      heart transplantation is due to a higher mortality within the first month after
      transplantation as a result of early graft failure. Strategies to improve donor
      heart function at implantation would have the greatest impact on survival after
      infant cardiac transplantation.

PMID- 9236439
TI  - Long-term sequential changes in exercise capacity and chronotropic responsiveness
      after cardiac transplantation.
AB  - BACKGROUND: Peak exercise capacity improves early after orthotopic cardiac
      transplantation. However, the physiological response to exercise remains
      abnormal, with a reduced rate of heart rate (HR) rise and reductions in peak
      exercise HR and the increment in HR from rest to peak exercise. This chronotropic
      incompetence is due in large part to cardiac denervation. If reinnervation occurs
      after transplantation, it might result in an improvement in both chronotropic
      responsiveness and maximal exercise capacity. We therefore hypothesized that the
      chronotropic response to exercise and maximal exercise capacity would improve
      with time after transplantation. METHODS AND RESULTS: Peak symptom-limited
      cardiopulmonary exercise tests performed in 57 clinically stable cardiac
      transplant recipients (mean age, 45 +/- 2 years) serially for up to 5 years after
      transplantation and in 33 control subjects without heart disease were analyzed
      retrospectively. Pretransplantation exercise tests were also performed in 41
      patients an average of 4.7 +/- 0.6 months before transplantation. At 1 year after
      transplantation, peak oxygen consumption was 16.6 +/- 0.9 mL.kg-1.min-1,
      reflecting a 43% increase versus pretransplantation. Nevertheless, compared with
      control subjects, maximal exercise capacity and the HR response to exercise were
      subnormal in transplant recipients. There were no further increases in peak
      exercise capacity, peak exercise HR, or the peak increment in HR with exercise up
      to 5 years after transplantation. CONCLUSIONS: One year after cardiac
      transplantation, peak exercise capacity and chronotropic responsiveness are
      subnormal. There is no further improvement in peak exercise capacity or
      chronotropic responsiveness as late as 5 years after transplantation. These data
      indicate that with regard to chronotropic responsiveness, functionally
      significant cardiac reinnervation does not occur between the first and fifth
      years after transplantation.

PMID- 9236440
TI  - Effect of sympathoinhibition on exercise performance in patients with heart
      failure.
AB  - BACKGROUND: In patients with heart failure, excessive sympathetic activation
      during exercise could interfere with exercise performance by impairing arteriolar
      dilation in working muscle and by adversely altering skeletal muscle metabolic
      behavior. To test this hypothesis, we examined the effect of sympathoinhibition
      with clonidine, a central sympatholytic agent, on skeletal muscle blood flow and
      metabolism in patients with heart failure. METHODS AND RESULTS: Swan-Ganz and
      femoral venous catheters were inserted in 20 patients with chronic heart failure
      and exercise intolerance (peak exercise VO2 = 9.3 +/- 1.4 [SEM] mL.min-1.kg-1).
      Central hemodynamic measurements, leg blood flow determined by thermodilution,
      and systemic and leg metabolic parameters were measured during maximal treadmill
      exercise before and 2 hours after clonidine 2 micrograms/kg IV (n = 15) or 0.9%
      normal saline (n = 5). During-control exercise before the administration of
      clonidine, leg blood flow increased from 0.3 +/- 0.1 to 1.8 +/- 0.2 L/min and
      plasma norepinephrine increased from 485 +/- 61 to 2155 +/- 186 pg/mL (both P <
      .01). Treatment with clonidine markedly suppressed norepinephrine levels during
      exercise (matched peak exercise workload: control, 2137 +/- 187 versus clonidine,
      1430 +/- 161 pg/mL), increased leg blood flow (control, 1.8 +/- 0.2 versus
      clonidine, 2.3 +/- 0.4 L/min), reduced systemic oxygen consumption (control, 1002
      +/- 70 versus clonidine, 966 +/- 68 mL/min), reduced pulmonary artery lactate
      concentration (control, 3.2 +/- 0.3 versus clonidine, 2.6 +/- 0.2 mEq/L), and
      decreased minute ventilation (control, 39.7 +/- 2.1 versus clonidine, 34.9 +/-
      2.4 L/min) (all P < .05). CONCLUSIONS: These findings suggest that sympathetic
      activation during exercise reduces leg blood flow, increases muscle glycolysis,
      and decreases muscle efficiency in patients with heart failure.

PMID- 9236441
TI  - Abnormal awake respiratory patterns are common in chronic heart failure and may
      prevent evaluation of autonomic tone by measures of heart rate variability.
AB  - BACKGROUND: Reduced heart rate variability, particularly in the Very-low
      frequency (VLF) spectral band, has been found to be a marker for poor prognosis
      in patients after myocardial infarction, but the origin of the VLF oscillations
      is unclear. In this study, we demonstrate that the power of cardiovascular
      oscillations in the VLF band in awake patients with mild to severe chronic heart
      failure is greatly increased by the common occurrence of unrecognized
      irregularity of breathing, which may confound the use of heart rate variability
      measures as indexes of autonomic tone or prognosis. METHODS AND RESULTS: Among
      110 consecutive patients referred for consideration of transplantation, 90 were
      in sinus rhythm, of whom 10 were excluded as unstable. The remaining 80 patients
      underwent recordings of ECG, beat-to-beat arterial oxygen saturation (SaO2), and
      respiration during both spontaneous and controlled breathing. During spontaneous
      awake breathing, 64% showed periodic breathing or Cheyne-Stokes respiration
      (CSR), which was associated with dominant power in the VLF band of all signals.
      This VLF power accounted for 55%, 77%, and 87% of heart rate variability,
      respectively, in patients with normal breathing, periodic breathing, and CSR. It
      was reduced by 48% and 62%, respectively, during controlled breathing in patients
      with periodic breathing or CSR. Controlled ventilation also improved oxygen
      saturation and markedly reduced its variability. CONCLUSIONS: Breathing disorders
      are surprisingly common in awake patients with poor left ventricular function and
      produce large VLF oscillations in heart rate variability. If measures of heart
      rate variability are used for prognostic purposes during both short-term and long
      term recordings, the confounding effects of variable respiratory patterns should
      be excluded. Respiratory rehabilitation might help control potentially hazardous
      surges in sympathetic tone.

PMID- 9236442
TI  - Low-energy cardioversion of spontaneous atrial fibrillation. Immediate and long
      term results.
AB  - BACKGROUND: Recent studies have suggested that induced atrial fibrillation (AF)
      could be successfully terminated by using a two-catheter electrode system and low
      energy (< 400 V). This study evaluated the efficacy and safety of low-energy
      cardioversion in spontaneous chronic and paroxysmal AF. METHODS AND RESULTS:
      Forty-two consecutive patients with spontaneous AF underwent low-energy
      electrical cardioversion. AF was chronic (> or = 1 month) with a mean duration of
      9 +/- 19 months in 28 patients (group I) or paroxysmal with a history of
      recurrent attacks and a mean duration of the present episode of 7 +/- 16 days in
      14 patients (group II). An underlying heart disease was present in 28 patients. A
      3/3-ms biphasic shock was delivered between catheters positioned in the right
      atrium and the coronary sinus in 32 patients. In 10 patients, the left pulmonary
      artery branch was used. The catheters were connected to a custom external
      defibrillator. The shocks were synchronized to the R wave. Following a test shock
      of 60 V, the energy was increased in 40-V steps until a maximum of 400 V or
      restoration of sinus rhythm. Sinus rhythm was restored in 22 of the 28 patients
      (78%) of group I by using a mean leading-edge voltage of 297 +/- 57 V (mean
      energy 3.3 +/- 1.3 J) and in 11 of 14 patients (78%) of group II by using a mean
      leading-edge voltage of 223 +/- 41 V (mean energy, 1.8 +/- 0.7 J). The energy
      required for terminating chronic AF was significantly (P < .001) higher than that
      required for terminating paroxysmal AF. Among the other variables studied, the
      duration of AF significantly affected the successful voltage. Ventricular
      proarrhythmia occurred in 1 patient with atrial flutter due to an unsynchronized
      shock. Of the 22 patients of group I in whom sinus rhythm was restored, 14 (63%)
      remained in sinus rhythm with a mean follow-up of 9 +/- 3 months. Pain level
      showed a good correlation with increasing voltage. However, a marked inter
      individual variation was noted. CONCLUSIONS: Atrial defibrillation using low
      energy between two intracardiac catheters with an electrical field between the
      right and left atria and the protocol used is feasible in patients with
      persistent spontaneous AF. The technique is safe provided synchronization to the
      R wave is achieved. A low recurrence rate of AF was seen in patients in whom
      sinus rhythm was restored.

PMID- 9236443
TI  - Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the
      THEOPACE study: a randomized controlled trial.
AB  - BACKGROUND: Pacemakers and theophylline are currently being used to relieve
      symptoms in patients with sick sinus syndrome (SSS). However, the impact of
      either therapy on the natural course of the disease is unknown. We conducted a
      randomized controlled trial to prospectively assess the effects of pacemakers and
      theophylline in patients with SSS. METHODS AND RESULTS: One hundred seven
      patients with symptomatic SSS (age, 73 +/- 11 years) were randomized to no
      treatment (control group, n = 35), oral theophylline (n = 36), or dual-chamber
      rate-responsive pacemaker therapy (n = 36). They were followed for up to 48
      months (mean, 19 +/- 14 months). During follow-up, the occurrence of syncope was
      lower in the pacemaker group than in the control group (P = .02) and tended to be
      lower than in the theophylline group (P = .07). Heart failure occurred less often
      in patients assigned to pacemaker therapy and theophylline than in control
      patients (both, P = .05), whereas the incidence of sustained paroxysmal
      tachyarrhythmias, permanent atrial fibrillation, and thromboembolic events did
      not show any apparent difference among the three groups. Heart rate was higher in
      the theophylline group than in the control group. Both pacemaker therapy and
      theophylline improved symptom scores after 3 months of treatment; however, a
      similar improvement was observed in the control group. CONCLUSIONS: In patients
      with symptomatic SSS, therapy with theophylline or dual-chamber pacemaker is
      associated with a lower incidence of heart failure; pacemaker therapy is also
      associated with a lower incidence of syncope. The therapeutic benefits of
      pacemakers and theophylline on symptoms are partly a result of spontaneous
      improvement of the disease.

PMID- 9236444
TI  - A population-based method for the estimation of defibrillation energy
      requirements in humans. Assessment of time-dependent effects with a transvenous
      defibrillation system.
AB  - BACKGROUND: A weighted logistic regression analysis was developed to allow
      pooling of patient data for the study of the stability of defibrillation energy
      requirements with a new nonthoracotomy lead defibrillation system. METHODS AND
      RESULTS: One hundred twenty patients were prospectively studied with a single
      model nonthoracotomy implantable cardioverter defibrillator (ICD) system at the
      time of implant and at 3 months. The pooled data of all shocks delivered to all
      patients were fitted to a logistic function to construct a defibrillation
      voltage/energy dose-response relationship. The crude logit curve was weighted in
      quartiles according to the average shock energy delivered per patient. Shocks at
      implant (n = 802; 6.6 +/- 2.5 shocks/patient) and follow-up (n = 292; 2.4 +/- 1.2
      shocks/patient) were analyzed. The modeled voltage/energy required for 50%
      successful defibrillation (95% CI) in the pooled data was 367 V (273, 461) and
      9.8 J (6.7, 12.9) at implant and 338 V (264, 412) and 10.5 J (8, 13.0) at follow
      up. The conventional measure of lowest successful voltage/energy (95% CI) was 430
      V (411, 449) and 12.1 J (11, 13.2) at implant and 415 V (391, 439) and 11.3 J
      (10, 12.6) at follow-up. There were no statistically significant differences
      between implant and follow-up energy requirements with either method.
      CONCLUSIONS: The nonthoracotomy lead system used in this study demonstrated
      stability of defibrillation energy requirements at implant and 3-month follow-up.
      A new technique for the estimation of the defibrillation energy dose-response
      relationship was derived by using a weighted logistic regression analysis.

PMID- 9236445
TI  - Heart rate during obstructive sleep apnea depends on individual hypoxic
      chemosensitivity of the carotid body.
AB  - BACKGROUND: In patients with obstructive sleep apnea syndrome (OSAS), there are
      cyclic fluctuations in heart rate (HR), that is, bradycardia during apnea
      followed by abrupt tachycardia on resumption of ventilation. Although a previous
      study suggested that the degree of bradycardia observed during central apnea at
      high altitude was determined by individual hypoxic chemosensitivity of the
      carotid body, it is not known whether this is true for subjects with obstructive
      sleep apnea syndrome. METHODS AND RESULTS: First, we examined apnea-associated HR
      changes in II subjects with OSAS and analyzed the relationship of the HR change
      during apnea (delta HR, defined as the difference between the values at the
      beginning and the end of apnea) and apnea-induced nadir SaO2 in each subject.
      Second, we conducted an apnea-simulation study in 7 subjects to examine whether
      the individual pattern of delta HR could be simulated while they held their
      breath under different levels of arterial oxygenation. The delta HR was highly
      variable among subjects: 2 showed an increase in HR during apnea, 6 a decrease,
      and the other 3 a borderline-type response. The slope factor of the nadir of the
      SaO2-delta HR line obtained from each subject had a significant correlation with
      the HR change during breath-holding conducted under normoxia (Spearman's rank
      correlation coefficient, rs = 69, P < .05) or hypoxia (rs = .81, P < .05) but not
      under hyperoxia. Finally, we evaluated hypoxic chemosensitivity of the carotid
      body by measuring the ventilatory response to isocapnic progressive hypoxia in
      all subjects. The magnitude of the ventilatory response ranged from 0.05 to 1.89
      L.min-1.%SaO2 fall-1 and showed a significant correlation with the slope factor
      of the nadir of the SaO2-delta HR line (rs = -.64, P < .05). CONCLUSIONS: The
      intersubject variation of the HR changes during sleep apnea can be explained in
      large part by individual hypoxic chemosensitivity of the carotid body regardless
      of the type of apnea.

PMID- 9236446
TI  - Sympathetic and vascular effects of short-term passive smoke exposure in healthy
      nonsmokers.
AB  - BACKGROUND: The physiological effects of cigarette smoking have been widely
      studied; however, little is known about the effects of acute exposure to
      sidestream smoke (passive smoking). We examined the effects of sidestream smoke
      on muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR)
      at rest and during stressful stimuli, including the cold pressor test (CPT),
      sustained handgrip (SHG), and mental stress (MS). METHODS AND RESULTS: In 17
      healthy nonsmokers, blood pressure (BP), heart rate (HR), forearm blood flow
      (venous occlusion plethysmography), FVR, and MSNA (obtained through direct
      intraneural recordings) were measured before and during inhalation of sidestream
      smoke in one session (n = 16) and before and during vehicle (air) inhalation in
      another session (n = 17) on a separate day. The order of sessions was randomized
      between subjects. Responses to CPT, SHG, and MS were measured before and after
      inhalation of smoke or vehicle (ie, twice during each session). After 15 minutes'
      exposure to sidestream smoke, plasma nicotine and carboxyhemoglobin levels
      increased to 0.77 +/- 0.11 ng/mL and 0.36 +/- 0.04% (mean +/- SEM, P < .05),
      respectively. Sidestream smoke, but not vehicle inhalation, increased resting
      MSNA from 23 +/- 2 to 28 +/- 2 bursts/min (P < .05). FVR increased with passive
      smoking, but this increase was not significantly different from the change in FVR
      with vehicle. Plasma norepinephrine and epinephrine, BP, and HR were not changed
      significantly by sidestream smoke. The responses of MSNNA, BP, HR, and FVR to the
      stressful stimuli were not potentiated by sidestream smoke, except for an
      increased BP response to the CPT (P < .05). CONCLUSIONS: Acute short-term passive
      (sidestream) smoke exposure elicits a modest increase in MSNA in healthy non
      smokers but does not change HR, BP, or FVR.

PMID- 9236447
TI  - Mobile thromboses of the aortic arch without aortic debris. A transesophageal
      echocardiographic finding associated with unexplained arterial embolism. The
      Filiale Echocardiographie de la Societe Francaise de Cardiologie.
AB  - BACKGROUND: Atherosclerotic lesions of the aortic arch are potential sources of
      arterial embolism. Mobile thrombi in the aortic arch in young patients without
      diffuse atherosclerosis have been reported recently, but such cases remain
      exceptional. We describe a series of young patients with unexplained arterial
      embolism in whom transesophageal echocardiography detected mobile aortic arch
      thromboses. METHODS AND RESULTS: Transesophageal echocardiography files collected
      between 1991 and 1995 in French academic cardiology centers were reviewed to
      identify patients who fulfilled the following criteria: (1) an arterial embolic
      event in the preceding weeks; (2) a mobile pedunculated aortic arch thrombosis,
      defined as an echogenic mass protruding into the lumen of the aorta and inserted
      on the aortic arch; and (3) absence of obvious diffuse aortic atherosclerosis or
      of aortic debris on transesophageal echocardiography. Twenty-three cases were
      identified from 27 855 examinations. Thromboses were located on the horizontal
      aorta (n = 4), near the ostium of the left subclavian artery (n = 5), or on the
      concavity of the posterior segment of the aortic arch (in the isthmus) (n = 14).
      The insertion site was a small atherosclerotic plaque in 21 patients. The
      remaining aortic wall always appeared normal or mildly atherosclerotic. The mean
      age of the patients was 45 +/- 8.4 years (range, 26 to 61 years). All patients
      were treated with intravenous heparin after the diagnosis of aortic arch
      thrombosis, and surgical removal of the thrombosis was performed in 10 patients
      in whom histological examination confirmed an atherosclerotic process at the site
      of insertion of the thrombosis. The prognosis was mainly influenced by embolic
      events. CONCLUSIONS: Thromboses of the aortic arch appear to be a variant form of
      aortic atherosclerotic disease associated with arterial embolism in young
      patients.

PMID- 9236448
TI  - Glucocorticoid receptor regulates expression of L-selectin and CD11/CD18 on human
      neutrophils.
AB  - BACKGROUND: Recent studies have raised the hypothesis that glucocorticoids could
      diminish the ability of endothelial cells to direct leukocyte traffic into
      inflamed tissues by inhibiting expression of the adhesion molecules endothelial
      leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. The aim of
      the present study was to investigate whether glucocorticoids also regulate the
      expression of L-selectin and CD11/CD18 integrins on human neutrophil
      granulocytes. METHODS AND RESULTS: Incubation of human whole blood with platelet
      activating factor (PAF, 1 mumol/L) evoked downregulation of L-selectin and
      upregulation of CD11/CD18 adhesion receptors on neutrophils as measured by flow
      cytometry. While dexamethasone (0.1 nmol/L to 100 mumol/L) did not affect
      expression of adhesion molecules on resting neutrophils, it attenuated the PAF
      induced changes in L-selectin and CD18 expression in a time- and concentration
      dependent fashion with IC50 values of 31 and 13 nmol/L, respectively. These
      effects of dexamethasone were completely aborted by RU-486 (10 mumol/L), which
      blocks transcriptional activation of the glucocorticoid receptor, and by the
      protein synthesis inhibitor cycloheximide (35.5 mumol/L). Dexamethasone, up to a
      concentration of 1 mumol/L, neither affected significantly the release of granule
      enzymes nor interfered with PAF binding to its membrane receptors. CONCLUSIONS:
      Our results show that glucocorticoids at clinically relevant concentrations exert
      specific actions on expression of adhesion molecules on activated neutrophils,
      which are mediated through ligation of glucocorticoid receptors and induction of
      protein synthesis, and suggest a novel mechanism by which anti-inflammatory
      corticosteroids may inhibit leukocyte accumulation.

PMID- 9236449
TI  - Workplace demands, economic reward, and progression of carotid atherosclerosis.
AB  - BACKGROUND: Characteristics of the work environment have been associated with
      cardiovascular morbidity and mortality, but it is unclear whether these factors
      are associated with preclinical manifestations of disease. METHODS AND RESULTS:
      We investigated the association between job demands, economic reward, and the 4
      year progression of carotid atherosclerosis in a population-based sample of 940
      Finnish men. Data from the Kuopio Ischemic Heart Disease Risk Factor Study were
      used to estimate changes in plaque height, maximum and mean intima-media
      thicknesses across combinations of job demands, and income. Associations were
      examined in relation to atherosclerotic risk factors and were stratified by
      baseline levels of atherosclerosis and prevalent ischemic heart disease. Men who
      had jobs with high demands and low economic rewards had significantly greater 4
      year progression of plaque height (0.33 mm, P = .008) and maximum intima-media
      thickness (0.32, P = .03) than men with low-demand, high-income jobs. The
      magnitude of these differences was not greatly attenuated by risk factor
      adjustment and did not differ when examined by the level of workplace resources,
      social support, or employment status. Larger differences were observed in a
      subsample of men who had more advanced atherosclerosis at baseline. CONCLUSIONS:
      These results show that men with demanding work that produces little economic
      reward have significantly greater progression of carotid atherosclerosis than
      more advantaged men. The relationship between job demands and health should be
      understood in a broad framework of interacting economic conditions, social
      circumstances, and behaviors that cascade over the life course and may ultimately
      contribute to socioeconomic inequalities in morbidity and mortality.

PMID- 9236450
TI  - Hemodynamic patterns of age-related changes in blood pressure. The Framingham
      Heart Study.
AB  - BACKGROUND: We attempted to characterize age-related changes in blood pressure in
      both normotensive and untreated hypertensive subjects in a population-based
      cohort from the original Framingham Heart Study and to infer underlying
      hemodynamic mechanisms. METHODS AND RESULTS: A total of 2036 participants were
      divided into four groups according to their systolic blood pressure (SBP) at
      biennial examination 10, 11, or 12. After excluding subjects receiving
      antihypertensive drug therapy, up to 30 years of data on normotensive and
      untreated hypertensive subjects from biennial examinations 2 through 16 were
      used. Regressions of blood pressure versus age within individual subjects
      produced slope and curvature estimates that were compared with the use of ANOVA
      among the four SBP groups. There was a linear rise in SBP from age 30 through 84
      years and concurrent increases in diastolic blood pressure (DBP) and mean
      arterial pressure (MAP); after age 50 to 60 years, DBP declined, pulse pressure
      (PP) rose steeply, and MAP reached an asymptote. Neither the fall in DBP nor the
      rise in PP was influenced significantly by removal of subsequent deaths and
      subjects with nonfatal myocardial infarction or heart failure. Age-related linear
      increases in SBP, PP, and MAP, as well as the early rise and late fall in DBP,
      were greatest for subjects with the highest baseline SBP; this represents a
      divergent rather than parallel tracking pattern. CONCLUSIONS: The late fall in
      DBP after age 60 years, associated with a continual rise in SBP, cannot be
      explained by "burned out" diastolic hypertension or by "selective survivorship"
      but is consistent with increased large artery stiffness. Higher SBP, left
      untreated, may accelerate large artery stiffness and thus perpetuate a vicious
      cycle.

PMID- 9236451
TI  - Crystalloid versus cold blood cardioplegia and cardiac troponin I release.
AB  - BACKGROUND: Cardiac troponin I (CTnI) has been shown to be a marker of myocardial
      injury. The aim of this study was to compare antegrade crystalloid cardioplegia
      with antegrade cold blood cardioplegia with warm reperfusion using CTnI release
      as the criteria for evaluating the adequacy of myocardial protection. METHODS AND
      RESULTS: Seventy patients were randomly assigned to receive crystalloid or blood
      cardioplegia. CTnI concentrations were measured in serial venous blood samples
      drawn just before cardiopulmonary bypass and after aortic unclamping at 6, 9, 12,
      and 24 hours and daily thereafter for 5 days. ANOVA with repeated measures was
      performed to test the effect of the type of cardioplegia on CTnI release. The
      total amount of CTnI released was higher in the crystalloid cardioplegia group
      than in the blood cardioplegia group (11.2 +/- 8.9 versus 7.8 +/- 8.6 micrograms,
      P < .02). CTnI concentration was significantly higher in the crystalloid group
      than in the blood group in the samples drawn at hours 9 and 12. Three patients in
      each group had ECG evidence of perioperative myocardial infarction. Eight
      patients in the crystalloid group and five patients in the blood group had CTnI
      evidence of perioperative myocardial infarction. CTnI release was significantly
      lower in patients requiring no electrical defibrillation after aortic unclamping.
      CONCLUSIONS: Cold blood cardioplegia followed by warm reperfusion is beneficial
      in an unselected group of patients with a preserved left ventricular function
      undergoing an elective first coronary artery bypass grafting. CTnI allowed the
      diagnosis of small perioperative necrotic myocardial areas. The need for
      electrical defibrillation after aortic unclamping was related to a higher release
      of CTnI. A further study is necessary to determine whether this technique was
      beneficial because of cold blood cardioplegia, warm reperfusion, or both.

PMID- 9236452
TI  - Comparison of human tissues and mechanical prostheses for aortic valve
      replacement in children.
AB  - BACKGROUND: Aortic valve replacement in children is problematic because of
      complications of mechanical valves and uncertain outcomes associated with human
      valves. The results of pediatric aortic valve replacements over 5 years were
      reviewed. METHODS AND RESULTS: Mechanical valves were used exclusively during the
      first part of this series (n = 26). Thereafter, 25 consecutive aortic valve
      replacements were performed with autografts (n = 19) or allografts (n = 6).
      Allografts were used for Marfan's syndrome patients or those with unusable
      pulmonary valves. Among autograft/allograft recipients, 16 patients underwent 27
      prior operations. In the mechanical group, 18 patients underwent 19 previous
      operations. Three patients in each group underwent a previous mechanical aortic
      valve replacement. Operative complications included two mild strokes and one
      pacemaker in the autograft/allograft group and three deaths and two pacemakers in
      the mechanical group. One autograft recipient required reoperation for pulmonary
      allograft stenosis. In the mechanical group, late complications included six
      cases of nonstructural degeneration and two cases of endocarditis, with three
      reoperations. Reoperation-free survival was 96% at 2 years in the
      autograft/allograft group and 80% at 2 years and 75% at 3 years in the mechanical
      group. Event-free survival was 96% at 2 years in the autograft/allograft group
      compared with 67% at 2 years and 49% at 3 years in the mechanical group (P <
      .05). CONCLUSIONS: The frequency of reoperations for mechanical aortic valve
      replacement has been surprisingly high. Aortic valve replacement in children with
      only autografts or allografts achieves good early results.

PMID- 9236453
TI  - Reoxygenation of hypoxic human umbilical vein endothelial cells activates the
      classic complement pathway.
AB  - BACKGROUND: Ischemia-reperfusion injury leads to the activation and endothelial
      deposition of complement. We investigated whether exposure of human umbilical
      vein endothelial cells (HUVECs) to hypoxia and/or reoxygenation activates
      complement and decreases HUVEC-surface expression of the C3 regulatory proteins
      CD46 and CD55. METHODS AND RESULTS: HUVECs were subjected to 0, 12, or 24 hours
      of hypoxia (O2 = 1%) and then reoxygenated for 3 hours (O2 = 21%) in the presence
      of 30% human serum. C3 deposition and HUVEC-surface expression of CD46 and CD55
      were evaluated by ELISA and flow cytometry. C3 deposition on HUVECs subjected to
      12 or 24 hours of hypoxia followed by 3 hours of reoxygenation was significantly
      greater than normoxic HUVECs. Inhibition of the classic but not the alternative
      complement pathway during reoxygenation attenuated C3 deposition. Western blot
      analysis of HUVEC lysates under reducing conditions demonstrated significantly
      increased iC3b deposition in hypoxic/reoxygenated HUVECs compared with normoxic
      HUVECs. FACS analysis confirmed iC3b deposition. HUVEC-surface expression of CD46
      and CD55 increases after hypoxia and/or reoxygenation. CONCLUSIONS: We conclude
      that (1) hypoxia and reoxygenation of HUVECs significantly increases iC3b
      deposition on HUVECs, (2) C3 deposition after hypoxia and reoxygenation is
      largely mediated by the classic complement pathway, and (3) HUVEC-surface
      expression of CD46 and CD55 increases after hypoxia and reoxygenation. These data
      demonstrate that hypoxia and reoxygenation of human endothelial cells activates
      the classic complement pathway despite an increase in complement C3 regulatory
      proteins.

PMID- 9236455
TI  - Images in cardiovascular medicine. Canyon T waves seen as narrowing of
      anterolateral T-wave inversions in a patient with recurrent chest pain presumed
      to be due to anterolateral ischemia.

PMID- 9236454
TI  - Relationships between myocardial bioenergetic and left ventricular function in
      hearts with volume-overload hypertrophy.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy secondary to volume overload can
      result in alterations in myocardial bioenergetics and LV dysfunction. This study
      examined whether bioenergetic abnormalities contribute to the pump dysfunction.
      METHODS AND RESULTS: Severe mitral regurgitation (MR) was produced in 10 dogs by
      disruption of the chordal apparatus. Hemodynamics and ventricular function were
      examined 11.7 months later under baseline conditions and during treadmill
      exercise. Myocardial high-energy phosphates were measured by using magnetic
      resonance spectroscopy at rest, during coronary vasodilation with adenosine, and
      during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused
      a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the
      hemodynamic and LV function were normal at rest, but abnormalities developed
      during beta-blockade and exercise. Myocardial creatine phosphate-to-ATP ratios
      were significantly lower in each layer across the LV wall in MR hearts than
      normal hearts. Myocardial blood flow and coronary reserve were normal in MR
      hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics.
      Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and
      dobutamine infusion well. CONCLUSIONS: In volume-overloaded LV hypertrophied
      hearts, alterations in myocardial high-energy phosphate levels do not induce
      abnormal mechanical performance at rest but may be related to a decreased
      contractile reserve during exercise.

PMID- 9236456
TI  - ACC/AHA guidelines for exercise testing: executive summary. A report of the
      American College of Cardiology/American Heart Association Task Force on Practice
      Guidelines (Committee on Exercise Testing).

PMID- 9236457
TI  - How to implement physical activity in primary and secondary prevention. A
      statement for healthcare-professionals from the Task Force on Risk-reduction,
      American Heart Association.

PMID- 9236458
TI  - Prevention of bacterial endocarditis. Recommendations by the American Heart
      Association.
AB  - OBJECTIVE: To update recommendations issued by the American Heart Association
      last published in 1990 for the prevention of bacterial endocarditis in
      individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group
      appointed by the American Heart Association for their expertise in endocarditis
      and treatment with liaison members representing the American Dental Association,
      the Infectious Diseases Society of America, the American Academy of Pediatrics,
      and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The
      recommendations in this article reflect analyses of relevant literature regarding
      procedure-related endocarditis, in vitro susceptibility data of pathogens causing
      endocarditis, results of prophylactic studies in animal models of endocarditis,
      and retrospective analyses of human endocarditis cases in terms of antibiotic
      prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database
      searches from 1936 through 1996 were done using the root words endocarditis,
      bacteremia, and antibiotic prophylaxis. Recommendations in this document fall
      into evidence level III of the US Preventive Services Task Force categories of
      evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing
      group after specific therapeutic regimens were discussed. The consensus statement
      was subsequently reviewed by outside experts not affiliated with the writing
      group and by the Science Advisory and Coordinating Committee of the American
      Heart Association. These guidelines are meant to aid practitioners but are not
      intended as the standard of care or as a substitute for clinical judgment.
      CONCLUSIONS: Major changes in the updated recommendations include the following:
      (1) emphasis that most cases of endocarditis are not attributable to an invasive
      procedure; (2) cardiac conditions are stratified into high-, moderate-, and
      negligible-risk categories based on potential outcome if endocarditis develops;
      (3) procedures that may cause bacteremia and for which prophylaxis is recommended
      are more clearly specified; (4) an algorithm was developed to more clearly define
      when prophylaxis is recommended for patients with mitral valve prolapse; (5) for
      oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a
      follow-up antibiotic dose is no longer recommended, erythromycin is no longer
      recommended for penicillin-allergic individuals, but clindamycin and other
      alternatives are offered; and (6) for gastrointestinal or genitourinary
      procedures, the prophylactic regimens have been simplified. These changes were
      instituted to more clearly define when prophylaxis is or is not recommended,
      improve practitioner and patient compliance, reduce cost and potential
      gastrointestinal adverse effects, and approach more uniform worldwide
      recommendations.

PMID- 9236459
TI  - The World Wide Web is already changing medical education.

PMID- 9236460
TI  - Designing an optimum rotation schedule for an ophthalmology residency.

PMID- 9236462
TI  - Videoconferencing systems.

PMID- 9236461
TI  - Community-based psychiatry clerkship in an ambulatory care setting.

PMID- 9236463
TI  - Perceptions of physicians' interpersonal skills.

PMID- 9236464
TI  - Possible influences of clerkship timing and site on residency choice.

PMID- 9236465
TI  - Medical education and managed care: can sour turn sweet?

PMID- 9236466
TI  - Rejecting conventional wisdom: how academic medical centers can regain their
      leadership positions.
AB  - Academic medical centers (i.e., medical schools and their principal hospitals)
      are following very similar strategies in attempts to secure their futures. It is
      likely that these undifferentiated strategies will fail, since most of them have
      been copied from the lower-cost, geographically better-positioned hospitals and
      health systems. Despite a wealth of innovative, entrepreneurial talent and the
      potential to reshape the world that AMCs live in, most AMCs are in reactive
      modes. Future directions and strategies are almost always shaped, forced, and
      justified by external pressures. The major problem with the strategic plans of
      most AMCs is that they are based on conventional industry wisdom. Strategic plans
      tend not to be analytically driven. The insight and understanding of those
      factors that drive the demand for AMCs' services and determine the performances
      of AMCs are lacking. The authors note some questions that are critical to the
      formulation of strategies for AMCs. For example, how can the research mission be
      changed from a cost-based to a value-based endeavor? Most AMCs cannot answer
      these questions, and if they do address them in the planning process, they do so
      superficially. Several examples of the factors that need to be understood are
      also given, such as patients' purposes and needs in seeking specialty care.
      Alternative strategies are listed, such as maintaining and exploiting the
      economic irrationality of the market rather than acting as if it were
      economically rational or forcing it to become so. Last, the authors outline the
      scope of the changes that are required and urge AMCs to reject conventional
      wisdom, determine their own unique situations, and work from there.

PMID- 9236467
TI  - Ownership and governance of university teaching hospitals: let form follow
      function.
AB  - Under the best of circumstances, the complex decision-making and resource
      allocation processes of a state university (and often of a variety of state
      agencies important to the university) significantly hinder the ability of the
      university-owned hospital to make changes critical to its financial and, hence,
      its programmatic success. At worst, as was the case for the University of
      Maryland Hospital a decade ago, the hospital can become capital-starved and
      operationally deficient under the bureaucratic mantle of the state and university
      and find itself unable to respond to the fast-changing market, placing its
      viability in jeopardy. To remedy this situation at the University of Maryland
      Hospital, in 1984 the state created a separate not-for-profit corporation, the
      University of Maryland Medical System ("the Medical system"), governed by its own
      board of directors, with a mandate to assure sound business practices,
      outstanding patient care, access to patients from across the state for tertiary
      care, access for the local disadvantaged community for comprehensive care, and
      attention to the academic mission of the university and its school of medicine.
      The results include strong financial performance, the ability to recapitalize
      outmoded facilities and technology, growth of strong programs, and the
      recruitment of excellent chairs and faculty. The Medical System's success
      suggests that university teaching hospitals, which necessarily depend on patient
      care revenues, may best be served by (1) removing them from university
      governance, thus allowing them to give primacy to their mission of patient care,
      and (2) removing them from state ownership, thus allowing them to use sound
      business practices in the competitive health care environment. The challenge
      under this arrangement is to ensure that the teaching hospitals can still support
      the educational and research programs that distinguish them. By establishing its
      independent, actively involved board of directors, the Medical System has
      successfully responded to this challenge.

PMID- 9236468
TI  - Ensuring the survival of the clinician-scientist.
AB  - Many forces threaten the survival of the clinician-scientist as an academic
      species, among them: (1) the changing health environment; (2) the complexity of
      and rapid advances in biomedical science, which necessitate that MD-PhD graduates
      "retool" after completing their clinical training; (3) the length and rigor of
      the research training required to train clinician-scientists adequately; (4) the
      scarcity of funding for subspecialty training positions; (5) the perception that
      the successful clinician-scientists in academic medicine are those who focus on
      basic, rather than clinical, research; (6) the indebtedness of young physicians
      when they complete medical schools; (7) the fierce competition for research
      funding; and (8) pessimism among senior faculty about the clinician-scientist's
      potential for survival. There are solutions to these issues that must be
      vigorously pursued to ensure the survival of the clinician-scientist: (1)
      Rigorous six- to seven-year programs (e.g., two in internal medicine, four to
      five in a subspecialty) for physicians must be established. They should include a
      minimum of three years of research and should lead to board certification in
      internal medicine, pediatrics, psychiatry, etc., board certification in a
      subspecialty, and a PhD in clinical science. (2) These programs must have a
      choice of three tracks, (a) disease-oriented basic research, (b) clinical
      investigation in patients, and (c) health services research. Such a program--the
      PhD in Clinical Science program--has recently been approved and begun at the
      University of Colorado. (3) Funding organizations such as the National Institutes
      of Health should designate their training resources primarily for programs with a
      minimum of three years of formal and rigorous research training. (4) These
      rigorous research training programs must be integrated with young-faculty awards
      for clinician-scientists to ensure continuity in their investigative careers. (5)
      Loan-repayment programs must be developed to repay student loans of clinician
      scientists during their first five years as faculty members. (6) Against the
      background of these changes, senior faculty as mentors must articulate to
      emerging clinician-scientists the excitement of being involved in future
      discoveries in biomedical science.

PMID- 9236469
TI  - Forum on the Future of Academic Medicine: Session I--Setting the stage.
AB  - In its first meeting, the Forum on the Future of Academic Medicine discussed the
      changes facing academic medicine in a competitive environment and at a time when
      medical schools and teaching hospitals are under pressure to conform to the
      market while preserving the traditional academic missions of teaching and
      research. The forum, created by the Association of American Medical Colleges and
      sponsored by The Robert Wood Johnson Foundation, will meet six times over the
      next two years to discuss a range of issues important to the success of academic
      medicine. Private-sector and academic members bring different perspectives to
      these discussions, which through their resource documents and meeting reports
      should stimulate thoughtful discussion throughout the academic medicine
      community. The forum members agreed that academic medicine has not been effective
      in defining its unique contributions to the health care system, but reached no
      consensus on how this deficit could best be remedied.

PMID- 9236470
TI  - A model to structure student learning in ambulatory care settings.
AB  - Providing students with an explicit framework for conducting patients' follow-up
      visits can ease students' transition into ambulatory care settings and enhance
      their learning. The authors describe a model that structures and defines
      students' tasks for a follow-up office visit. The model gives priority to the
      organization of patient care issues, the efficient use of patient and preceptor
      time, and the student's identification of a learning agenda for each patient
      encounter. In a rapidly expanding managed care world where physician and practice
      productivity are paramount, this model has the potential to enhance
      standardization of learning across diverse clinical sites and to increase the
      cost-effectiveness of teaching medical students in ambulatory settings. The
      authors have introduced this model in a half-day orientation for a primary care
      clerkship. Initial feedback suggests that the model is useful in preparing
      students to function more effectively in an ambulatory care setting.

PMID- 9236471
TI  - Recent implementations of electronic medical records in four family practice
      residency programs.
AB  - Electronic medical records (EMRs) are increasingly replacing paper records, and
      many residency program directors are interested in incorporating EMR systems into
      their clinics. The authors describe their experiences implementing EMRs in their
      family practice residency programs; the four programs are the Eau Claire Family
      Practice Residency Program, the Galveston Family Practice Residency Program, the
      Mayo-Scottsdale Residency Program, and the Wyoming Valley Family Practice
      Residency. The authors provide background information about each program and an
      overview of the EMR systems; they then describe the implementation processes,
      addressing training, integration with other software- and paper-based systems,
      security, costs, and effects on patient volume and staffing levels. Finally, they
      discuss the general benefits of and barriers to EMR-system implementations, and
      make recommendations for other programs considering implementing EMRs.

PMID- 9236472
TI  - Validating the standardized-patient assessment administered to medical students
      in the New York City Consortium.
AB  - PURPOSE: To test the criterion validity of existing standardized-patient (SP)
      examination scores using global ratings by a panel of faculty-physician observers
      as the gold-standard criterion; to determine whether such ratings can provide a
      reliable gold-standard criterion to be used for validity-related research; and to
      encourage the use of these gold-standard ratings for validation research and
      examination development, including scoring and standard setting, and for
      enhancing understanding of the clinical competence construct. METHOD: Five
      faculty physicians independently observed and rated videotaped performances of 44
      students from one medical school on the seven SP cases that make up the fourth
      year assessment administered at The Morchand Center of Mount Sinai School of
      Medicine to students in the eight member schools in the new York City Consortium.
      RESULTS: The validity coefficients showed correlations between scores on the
      examination and the overall ratings ranging from .60 to .70. The reliability
      coefficients for ratings of overall examination performance reached the commonly
      recommended .80 level and were very close at the case level, with interrater
      reliabilities generally in the .70 to .80 range. CONCLUSION: The results are
      encouraging, with validity coefficients high enough to warrant optimism about the
      possibility of increasing them to the recommended .80 level, based on further
      studies to identify those measurable performance characteristics that most
      reflect the gold-standard ratings. The high interrater reliabilities indicate
      that faculty-physician ratings of performance on SP cases and examinations can or
      may be able to provide a reliable gold standard for validating and refining SP
      assessment.

PMID- 9236473
TI  - The effect of right or left placement of the positive response on Likert-type
      scales used by medical students for rating instruction.
AB  - PURPOSE: To determine whether students' ratings of instruction demonstrate a
      primary effect, to determine whether the primacy effect relates to the number of
      response options, and to assess whether the primacy effect relates to how
      favorably the instructional activity is rated. METHOD: Inf 1995-96 six different
      forms of a 13-item course-evaluation questionnaire (with Likert-type items) were
      used to evaluate two second-year courses, Respiratory and Hepatic, at the
      University of Wisconsin Medical School; the first was one of the most highly
      rated courses at Wisconsin, and the second was less highly rated. The forms
      differed by whether they contained five, six, or seven response options, and
      whether the "strongly agree" rating was on the left side or the right side of the
      page. The second-year class that participated in the study comprised 140
      students. The six different forms of the course-evaluation questionnaires were
      randomly distributed to the students in equal numbers. Results were analyzed with
      a number of statistical methods. RESULTS: Completed questionnaires were obtained
      from 132 students (94%) in Respiratory and from 119 students (85%) in Hepatic.
      Overall, the forms with the positive rating on the left side had more positive
      ratings and less variance. For Respiratory, primacy affected the response
      variance. For Hepatic, primacy affected the response means. CONCLUSION: Faculty
      evaluation systems are increasingly using students' ratings for making important
      decisions regarding salaries, teaching assignments, tenure, etc. The evidence
      that the primacy effect influences such ratings highlights the need to
      standardize as much as possible how such ratings are obtained.

PMID- 9236474
TI  - The ability of first-year medical students to correctly identify and directly
      respond to patients' observed behaviors.
AB  - PURPOSE: To determine whether first-year medical students could correctly
      identify and directly respond to patients' observed behaviors. METHOD: In January
      1995, 166 first-year students at the University of Illinois College of Medicine
      were shown a videotape of six patients vignettes illustrating three types of
      patient behaviors (anger, seduction, and hypochondriasis) by pairs of men and
      women. After each vignette the tape was stopped, and in an open-ended format the
      students were asked to identify each patient's behavior and to write their verbal
      response to that patient. The students were prompted with the question, "What
      would you say now?" They were then asked to select their comfort level with each
      patient on a scale ranging from 1 (very comfortable) to 5 (very uncomfortable).
      The students' responses were analyzed with several statistical tools. RESULTS:
      The students correctly identified anger in both the man and the woman over 90% of
      the time. Forty percent of the students identified seductive behavior from the
      woman, but only 5% identified it from the man. Hypochondriacal behavior was
      identified 65% of the time in the woman and 49% of the time in the man.
      Identification of behavior did not correlate with the formation of a direct
      response. The students' gender did not predict the ability to correctly identify
      or directly respond to patients. However, student responses as a whole differed
      significantly based on the patient's gender. CONCLUSION: These findings
      underscore the complexity of physician-patient communications and the need to
      address the subtleties of these interactions as part of the medical school
      curriculum.

PMID- 9236475
TI  - Insights into medical students' career choices based on third- and fourth-year
      students' focus-group discussions.
AB  - PURPOSE: To identify previously unrecognized factors influencing medical
      students' career choices and to better characterize the effects of educational
      experiences, role models, and educational debt on career decisions. METHOD: Fifty
      two third- and fourth-year students were recruited from three California medical
      schools to participate in focus-group discussions. The students were assembled
      into 12 groups of about four classmates from the same school, each facilitated by
      a medical student from another school. Focus-group discussions were audiotaped
      and qualitatively analyzed using content analysis. RESULTS: The students'
      perceptions of their abilities to influence patients' outcomes and to cope with a
      large knowledge base differentiated those interested in primary care fields from
      those attracted to procedure-oriented specialties. Negative role models, based on
      the students' assessments of interpersonal interactions and career satisfaction,
      were particularly influential in closing doors to certain fields. Many of the
      women reported an absence of role models. Most of the students denied any effect
      of debt or potential income on career choice; while many cited their small debts,
      some of the women alluded to the anticipation of being in dual-income families.
      CONCLUSION: Students' career decisions are complex, dynamic, and individualized
      processes. The use of qualitative measures helps bolster understanding of these
      processes by identifying new factors (such as mastery of knowledge) and by
      further characterizing known factors (such as role models and financial
      considerations). A comprehensive and valid understanding of students' career
      decision making is necessary to develop successful strategies to sustain and
      encourage the choice of primary care careers.

PMID- 9236476
TI  - The effectiveness of formal evaluation sessions during clinical clerkships in
      better identifying students with marginal funds of knowledge.
AB  - PURPOSE: To compare evaluation methods for identifying third-year medical
      students whose funds of knowledge are marginal. METHOD: The written evaluation
      forms and comments from a formal evaluation session for 124 students in the
      inpatient medicine clerkship in 1992-93 at the Uniformed Services University of
      the Health Sciences F. Edward Hebert School of Medicine were reviewed. The
      written and verbal ratings of a student's general fund of knowledge were
      converted to similar five-point categorical scales. For each evaluation method,
      chi-square analysis was used to compare the students identified as having
      marginal funds of knowledge with those who scored < or = 300 on the end-of
      clerkship NBME subject examination. RESULTS: Sixteen students scored < or = 300
      on the NBME subject examination. For the checklist descriptors, ratings of
      "marginal" identified three of these 16 students (a sensitivity of 19%). For the
      written comments on the evaluation form, ratings of "marginal" identified four of
      the 16 (a sensitivity of 25%). For the formal evaluation session, however,
      ratings of "marginal" identified seven of the 16 (a sensitivity of 44%). The
      specificity of a "marginal" rating was excellent (> or = 95%) for all three
      evaluation methods. Chi-square analysis was significant for each method (p < or =
      .01). CONCLUSION: Although the ability of housestaff and faculty to identify
      students with weak funds of knowledge may be less than ideal, it may be improved
      by the routine use of a formal evaluation session. If done during the clerkship,
      this would allow for a specific plan of remediation to be designed with the
      instructors for the students at risk.

PMID- 9236477
TI  - The effect of a rolling admission policy on a medical school's selection of
      applicants.
AB  - PURPOSE: As the University of Kentucky College of Medicine (UKCM) employs a
      rolling admission policy, this study was designed to determine (1) whether the
      month during which applicants were considered by the UKCM admission committee was
      associated with admission status, (2) whether applicants considered early in the
      process differed in selected academic and noncognitive pre-admission
      characteristics in comparison with later applicants, and (3) what the importance
      of the month of the applicant's consideration was relative to other predictors of
      admission to UKCM. METHOD: The application files and admission committee's
      minutes regarding 302 applicants who received interviews during the 1993-94
      application cycle were examined. Data reviewed included each applicant's gender,
      age, geographic origin, undergraduate science and non-science grade-point
      averages, and Medical College Admission Test scores; the date of consideration by
      the committee; interviewers' ratings; the initial motion on the applicant; and
      the final admission status. RESULTS: The findings indicate that the applicants
      considered earlier were significantly more likely to gain admission. However,
      upon assigning the applicants to three groups according to the month of
      consideration, no difference in academic qualifications was found. Regression
      analyses revealed that despite the effect of time of consideration, noncognitive
      characteristics related to UKCM's mission also predicted admission decisions.
      CONCLUSION: This study provides useful information to admission committees
      reviewing the effect of a rolling admission policy, as well as to applicants and
      premedical advisors, who should be aware of the potential importance of
      submitting applications in a timely manner.

PMID- 9236478
TI  - The objectives of medical education: reflections in the accreditation looking
      glass.
AB  - The authors explored the extent to which medical schools have established
      institutional and departmentalized educational objectives, by examining the
      accreditation databases, institutional self-studies, and site visit reports of 59
      schools surveyed by the Liaison Committee on medical Education (LCME) in 1994
      1996. In this study, the individual school was the unit of analysis, and the
      dependent variables were statements--in outcomes' terms--of institutional and
      departmental learning objectives. Objectives were classified as "robust" when
      they were expressed as measurable learning outcomes in the domains of knowledge
      and skills and behaviors. Departmental objectives were assessed separately for
      core basic science courses and clinical clerkships. A number of independent
      variables were studied for their association with the elaboration of outcomes
      based educational objectives: centralized management of the curriculum,
      curricular reform, an office of education, an institutionalized faculty
      development program, problem-based learning, interdisciplinary teaching,
      systematized assessment of educational outcomes, and structured clinical skills
      assessment. Of the 59 schools, 15 (25%) had robust institutional objectives that
      identified items of measurable knowledge, skills, and behavior, while 44 (75%)
      had modest objectives, usually descriptions of the purpose of the curriculum,
      global statements about the knowledge and behavior qualities that students should
      acquire, and the subjects that instructors intended to tech. Schools with well
      articulated learning outcomes were more likely to have centralized management of
      the curriculum, a record of curricular reform, a program of problem-based
      learning, rich basic science course and clerkship objectives, and structured
      assessment of students' clinical skills. Well-stated and diverse educational
      objectives were found for basic science courses in only 13 of the 59 schools
      (22%). Thirty of the schools (51%) had clerkships with robust learning
      objectives, more commonly in the generalist specialties of pediatrics, family
      medicine, and internal medicine. Clerkships with stout objectives more often
      employed structured assessments of students' clinical skills. Schools that paid
      attention to the explication of learning objectives were more likely to link
      specific institutional and departmentalized outcomes with methods of evaluating
      students, in turn guiding the content and methods of instruction. Schools with
      vapid objectives attracted 40% more accreditation citations for shortcomings in
      curricular management, course and clerkship quality, and the evaluation of
      student achievement, especially in the clinical skills domain. In the future,
      accreditors should focus more closely on this association.

PMID- 9236479
TI  - Menopausal hormone therapy: physician awareness of patient attitudes.
AB  - BACKGROUND: Physicians need to be aware of their patients' attitudes toward
      menopause when counseling women regarding hormone therapy, because menopausal
      attitudes may affect women's satisfaction with their decisions to use or not to
      use hormone therapy. Our objectives were to assess physician awareness of patient
      attitudes on issues surrounding the menopause and hormone therapy, and to
      determine the prevalence and correlates of hormone use. METHODS: This cross
      sectional survey study was conducted in the primary care outpatient practices of
      an academic medical center. Surveys were simultaneously administered to female
      patients aged 50 to 70 years (n = 182) and their primary care physicians
      immediately after clinical encounters. The surveys contained questions from four
      established (five-point) attitudinal scales (autonomy, desire for information,
      philosophy of the menopause, barriers to use of hormone therapy), and questions
      addressing patients' degree of concern about developing various conditions.
      Physicians were asked to estimate their patients' attitudes. PATIENTS AND
      METHODS: Physicians were generally aware of patients' desire for autonomy (3.2
      versus 3.2, P = 1.0), but tended to underestimate patients' desire for
      information (3.7 versus 4.5, P = 0.0001) and patients' perceptions of barriers to
      using hormone therapy (3.2 versus 3.4, P = 0.0001). They also underestimated the
      extent to which patients view menopause as a medical problem (3.0 versus 3.2, P =
      0.0001). Physicians overestimated patients' general concern about heart disease
      (scale difference 0.40, P = 0.0001) and breast cancer (difference 0.23, P =
      0.02). Physicians were less aware of their patients' attitudes when they were
      male (versus female), interns/residents (versus faculty/fellows), and less
      knowledgeable about menopausal hormone therapy (versus more knowledgeable). The
      significant predictors of hormone use on multivariate analysis were past
      hysterectomy, urinary incontinence, alcohol intake, and possession of knowledge
      regarding hormone therapy. CONCLUSIONS: Physicians incorrectly estimate some
      aspects of their patients' attitudes regarding menopause and hormone therapy, and
      certain physician characteristics may be associated with decreased awareness. To
      optimize hormone therapy counseling, physicians may need to increase their
      attention to patients' menopausal attitudes.

PMID- 9236480
TI  - Determinants of compliance with anticoagulation: A case-control study.
AB  - BACKGROUND: The number of patients for whom long-term anticoagulation is
      indicated has increased dramatically over the past decade. Good patient
      compliance is necessary to safely realize the benefits of anticoagulation, yet
      barriers to compliance with anticoagulation therapy have not been studied.
      METHODS: We conducted a case-control study in the Anticoagulation Therapy Unit
      (ATU) at Massachusetts General Hospital. Forty-three patients who had been
      discharged from the ATU for noncompliance (cases) and 89 randomly selected
      compliant ATU controls were interviewed. Noncompliant cases had self-discontinued
      warfarin or were taking warfarin with inadequate monitoring of international
      normalized ratio (INR) levels. Telephone interviews assessed sociodemographic
      features, indication for anticoagulation, patient satisfaction, and health
      beliefs. RESULTS: Noncompliant cases were more likely to be younger (mean 53.7
      years versus 68.7 years, P < 0.0001), male (odds ratio [OR] 3.5, 95% confidence
      interval [CI] 1.5, 8.2) and nonwhite (OR 6.4, 95% CI 1.9, 21.9), and less likely
      to have had a stroke or transient ischemic attack (OR 0.2, 95% CI 0.1, 0.7). In
      open-ended questioning, cases were more likely to report that they did not know
      why warfarin had been prescribed (OR 4.4, 95% CI 1.4, 14.2). Noncompliant cases
      were more likely not to have a regular physician (OR 11.1, 95% CI 3.6, 50.0);
      among patients with a regular physician, noncompliant cases were more likely to
      feel dissatisfied. Examination of health beliefs revealed that noncompliant cases
      felt more burdened by taking warfarin, and perceived fewer health benefits.
      CONCLUSIONS: Patients who are noncompliant with warfarin share distinctive
      clinical characteristics. Notably, younger, male patients who have not
      experienced a thromboembolic event are more likely to forego INR testing or to
      stop anticoagulation therapy completely. Improved patient education, physician
      involvement, and ease of monitoring may improve compliance, particularly among
      younger male patients.

PMID- 9236481
TI  - Population-based surveillance for group A streptococcal necrotizing fasciitis:
      Clinical features, prognostic indicators, and microbiologic analysis of seventy
      seven cases. Ontario Group A Streptococcal Study.
AB  - PURPOSE: To determine the incidence of group A streptococcal necrotizing
      fasciitis in Ontario, Canada, and to describe the clinical features, outcome, and
      microbiologic characteristics of this infection. PATIENTS AND METHODS:
      Prospective, population-based surveillance for invasive group A streptococcal
      infections was conducted in Ontario from November 1991 to May 1995. All 77
      patients meeting clinical and/or histopathologic criteria for streptococcal
      necrotizing fasciitis were included. Demographic and clinical information was
      obtained by patient interviews and chart review. Group A streptococci were
      characterized by M-protein and T-agglutination typing, and polymerase chain
      reaction (PCR) detection of streptococcal pyrogenic exotoxin genes A and C (speA;
      speC). RESULTS: The incidence of group A streptococcal necrotizing fasciitis
      increased during the study from 0.085 per 100,000 population in the first year to
      0.40 per 100,000 population in the last year (P < 0.001). The median age of cases
      was 57.5 years and the rate of disease increased with increasing age. Seventy
      nine percent of cases were community-acquired, 11% were nosocomial, and 10% were
      acquired in a nursing home. Forty-seven percent of cases were associated with the
      presence of streptococcal toxic shock syndrome (Strep TSS) and 46% were
      bacteremic. Thirty-four percent of cases died and mortality was correlated with
      increasing age (P = 0.006), presence of hypotension (P = 0.01), and bacteremia (P
      = 0.03). The most common streptococcal serotypes were M1 (35%) and M3 (25%).
      Forty-one percent of strains possessed the speA gene and 30% the speC gene.
      Outcome was not correlated with M-type or the presence of spe genes. CONCLUSIONS:
      The incidence of necrotizing fasciitis caused by group A streptococcus increased
      in Ontario between 1992 and 1995. Elderly individuals were more likely to acquire
      the disease and to die from it. Mortality because of streptococcal necrotizing
      fasciitis was also associated with the presence of hypotension, Strep TSS, or
      bacteremia, but not with M-type or the presence of pyrogenic exotoxin genes.

PMID- 9236482
TI  - Incidence and risk of developing fungal prosthetic valve endocarditis after
      nosocomial candidemia.
AB  - PURPOSE: To determine the incidence of prosthetic valve endocarditis (PVE) in
      fungemic patients with prosthetic heart valves (PHV), estimate risk of subsequent
      PVE, and describe risk factors and diagnostic and therapeutic management issues
      in such patients. PATIENTS AND METHODS: This is a retrospective chart review in a
      1,100-bed tertiary referral center with an active cardiothoracic surgical
      service. Forty-four patients with PHVs developed nosocomial fungemia between
      January 1985 and April 1995. RESULTS: Of 44 patients, 33 never developed evidence
      of PVE (group 1), 7 (16%) had evidence of PVE at the time of candidemia (group
      2), and 4 (9%) developed PVE a mean of 232 days after candidemia (group 3).
      Predisposing factors including intravascular lines, prior antibiotic therapy, and
      an identifiable portal of entry for fungemia were common in group 1 but not group
      2. Candidemia occurred significantly later after PHV surgery in group 2 (mean 270
      days) as compared to groups 1 and 3 (means 48 and 15.5 days, respectively; P =
      0.02). Ten of 11 patients with Candida PVE (group 2 and 3) were treated with
      amphotericin B and valve replacement. Three relapses after combined therapy were
      documented in two patients. Mortality was significantly higher for patients
      without Candida PVE (group 1) as compared to patients with Candida PVE (groups 2
      and 3) at 1 month (53% vs 9%), 2 months (69% vs 20%) and 1 year (83% vs 25%)
      after candidemia. CONCLUSIONS: Patients with prosthetic heart valves who develop
      nosocomial candidemia are at notable risk of either having or developing Candida
      PVE months or years later. Late onset candidemia and lack of an identifiable
      portal of entry should heighten concern about Candida PVE in such patients.

PMID- 9236483
TI  - Prevalence and signification of antinuclear and anticardiolipin antibodies in
      patients with epilepsy.
AB  - PURPOSE: To determine the prevalence of autoantibodies in patients with epilepsy
      and to find a possible relationship between antinuclear antibodies (ANA) and/or
      anticardiolipin (aCL) antibodies and epilepsy. PATIENTS AND METHODS: One hundred
      sixty-three consecutive, unselected patients followed at the Centre Saint-Paul, a
      French medical center specialized in epilepsy, were included in the study. IgG
      and IgM class aCL antibodies were measured by an enzyme-linked immunosorbent
      assay (ELISA). IgG class ANA was detected by an indirect immunofluorescence
      technique with Hep2 cells as the substrate. Sera from 100 healthy blood donors,
      matched for age and sex, were used as controls. RESULTS: In 31 sera, IgG class a
      aCL antibodies were detected at a value higher than 17 GPL unit (19%, P =
      0.0003); 10 of them had a value higher than 35 GPL unit. IgM class aCL antibodies
      were not detected at a significant value. For 6 of the 31 sera, there was a beta
      2-glycoprotein I dependence. None of the patients with aCL antibodies in the
      serum had a past history of deep venous or arterial thrombosis. ANA were detected
      in the sera from 41 patients (25%, P < 0.005). The presence of autoantibodies in
      the serum was not statistically dependent on the type of epilepsy, the kind of
      antiepileptic drug, or the age or sex of the patients. CONCLUSIONS: Our study
      suggests that there is a relationship between epilepsy and aCL antibodies, even
      in the patients without systemic lupus erythematosus. Large prospective studies
      are needed to define the role of the aCL antibodies and ANA in pathophysiology of
      epilepsy.

PMID- 9236484
TI  - Intravenous immunoglobulin is ineffective in the treatment of patients with
      chronic fatigue syndrome.
AB  - PURPOSE: To determine whether the reported therapeutic benefit of intravenous
      immunoglobulin in patients with chronic fatigue syndrome (CFS) is dose dependent.
      PATIENTS AND METHODS: Ninety-nine adult patients, who fulfilled diagnostic
      criteria for CFS, participated in this double-blind, randomized, and placebo
      controlled trial. Patients received intravenous infusions with either a placebo
      solution (1% albumin) or one of three doses of immunoglobulin (0.5, 1, or 2 g/kg)
      on a monthly basis for 3 months, followed by a treatment-free follow-up period of
      3 months. Outcome was assessed by changes in a series of self-reported measures
      (quality-of-life visual analog scales, standardized diaries of daily activities,
      the profile of mood states questionnaire) and the Karnofsky performance scale.
      Cell-mediated immunity was evaluated by T-cell subset analysis and delayed-type
      hypersensitivity (DTH) skin testing. RESULTS: No dose of intravenous
      immunoglobulin was associated with a specific therapeutic benefit. Adverse
      reactions, typically constitutional symptoms, were reported by 70% to 80% of
      patients, with no relationship to immunoglobulin treatment. CONCLUSIONS:
      Intravenous immunoglobulin cannot be recommended as a therapy for the treatment
      of CFS. A better understanding of the pathophysiology of this disorder is needed
      before effective treatment can be developed.

PMID- 9236485
TI  - The overdiagnosis of fibromyalgia syndrome.
AB  - PURPOSE: As fibromyalgia syndrome (FM) has gained greater acceptance and
      awareness in both the medical and the lay community, the possibility of
      overdiagnosis exists. Diffuse body pain in a woman is likely to suggest this
      diagnosis. We report the diagnosis of FM in 11 female patients whose primary
      cause for musculoskeletal symptoms was spondyloarthritis rather than only FM.
      PATIENTS AND METHODS: Of a total of 321 new rheumatology referrals in a 1-year
      period, 35 (11%) were diagnosed with FM. A further 11 (3%) were referred with
      either a previous diagnosis of FM or a presumed diagnosis of FM in whom the
      musculoskeletal syndrome could be attributed to previously unrecognized
      spondyloarthropathy. RESULTS: The 11 female patients had mostly experienced
      musculoskeletal symptoms for prolonged periods of time ranging from 1 to 40
      years. Symptoms included prominent spinal pain involving at least 2 locations in
      the spine (n = 10), night pain that disturbed sleep (n = 10), and prolonged
      morning stiffness (n = 9). A previous history of enthesopathy, or history in the
      patient or first-degree relative of one of the seronegative associated diseases,
      such as psoriasis or ulcerative colitis, occurred in nine patients. Most patients
      had already undergone extensive investigations by various specialists in
      musculoskeletal medicine, but spondyloarthritis had only infrequently been
      considered a diagnostic possibility. CONCLUSION: Spondyloarthropathy in women may
      present subtly and have considerable overlap in symptomalogy with FM. A diagnosis
      of spondyloarthropathy should be considered in women with an ill-defined pain
      syndrome with prominent spinal pain and associated enthesopathy, or history or
      family history of seronegative-associated disease. It is possible that a primary
      diagnosis of FM is being made too freely, without consideration of other
      diagnoses, in the setting of ill-defined musculoskeletal pain.

PMID- 9236486
TI  - Antimicrobial resistance with focus on beta-lactam resistance in gram-negative
      bacilli.
AB  - beta-Lactam antibiotics are the most frequently prescribed antibiotics worldwide.
      Therefore, it is not surprising that resistance to this very important class of
      agents poses an increasingly complex and perplexing problem for physicians. Among
      the variety of mechanisms that can provide resistance to beta-lactam antibiotics
      in gram-negative bacilli, the production of beta-lactamase is by far the single
      most important factor. With the introduction of newer beta-lactam agents observed
      changes in beta-lactamases include the increased prevalence of older enzymes, the
      appearance of new enzymes, and alteration in the level of expression of the
      enzymes. These changes have been responsible for resistance to newer
      cephalosporins, monobactams, carbapenems, and beta-lactamase inhibitor/beta
      lactam drug combinations. Resistance to beta-lactam antibiotics has also emerged
      through alterations in the targets of the drugs, the penicillin-binding proteins,
      and through alterations in outer membrane permeability of the organisms to the
      drugs. With some beta-lactam agents, multiple mechanisms must be acquired before
      clinically relevant levels of resistance are attained. This is especially true
      for carbapenems and fourth generation cephalosporins. Nevertheless, resistance to
      beta-lactam antibiotics is on the rise among clinical isolates of gram-negative
      bacilli, and only through more judicious use of these agents can their usefulness
      for treatment and prevention of infections be preserved.

PMID- 9236487
TI  - Advances and controversies in the diagnosis and management of medullary thyroid
      carcinoma.
AB  - Recent advances in the diagnosis and treatment of medullary thyroid carcinoma
      (MTC) have been significant, but some issues remain controversial. MTC may occur
      either as a hereditary or a nonhereditary entity. Hereditary MTC can occur either
      alone--familial MTC (FMTC)--or as the thyroid manifestation of multiple endocrine
      neoplasia type 2 (MEN 2) syndromes (MEN 2A and MEN 2B). These hereditary
      disorders are due to germline mutations in the RET proto-oncogene. Early
      diagnosis and treatment considerably improve the prognosis in patients with MTC.
      Genetic testing can identify almost all affected individuals with hereditary
      disease and permits early thyroidectomy in gene carriers. Plasma CT is an
      excellent marker for postoperative follow-up. Imaging studies help delineate
      recurrent or metastatic lesions. Treatment of recurrent or metastatic disease is
      primarily surgical, including either palliative or microdissective surgery.
      Radiation therapy is reserved for skeletal metastasis or nonresectable metastatic
      MTC. Efficacy of current chemotherapy programs is not well established. Overall,
      the 10-year survival rates are approximately 65%.

PMID- 9236488
TI  - Popcorn, pica, and impaction.

PMID- 9236489
TI  - Hepatitis C-associated osteosclerosis: an unusual syndrome of acquired
      osteosclerosis in adults.

PMID- 9236490
TI  - Diabetes and epistaxis in a 57-year-old man.

PMID- 9236491
TI  - Exercise limits in chronic fatigue syndrome.

PMID- 9236492
TI  - Graded exercise testing and chronic fatigue syndrome.

PMID- 9236493
TI  - Building a healthy house.

PMID- 9236494
TI  - Clinical applications of cytokines: new directions in the therapy of atopic
      diseases.
AB  - OBJECTIVES: This review will enable the readers to understand the pathogenesis of
      allergic inflammation, and the role of various cells and cytokines in allergic
      diseases. Pathogenic cytokines may become key therapeutic targets in the future
      treatment of allergic diseases. DATA SOURCES: MEDLINE literature search limited
      to the English language was performed using the relation between specific
      cytokines and allergic inflammation as well as therapy of allergic diseases.
      Relevant articles referenced in retrieved sources and current texts on ctyokines
      and allergic responses were also utilized. RESULTS: The mechanism underlying
      allergic inflammation involves complex interactions between various cells and
      cytokines. The immediate reaction is caused mainly by mast cells and followed by
      a cell mediated response that involves eosinophils, mononuclear cells,
      neutrophils, T lymphocytes and macrophages. The majority of T cells in early
      allergic reactions are T helper type 2 (TH2)-like producing IL-4, IL-5, IL-13 but
      not IFN-gamma. These cytokines regulate IgE synthesis, promote eosinophil
      differentiation and survival, and induce vascular endothelial adhesion molecules,
      thus contributing to allergic inflammation. CONCLUSIONS: Although studies of
      cytokine modulation have utilized animal models of allergic diseases, the
      increasing availability of recombinant cytokines and cytokine antagonists is
      likely to lead to more wide scale applications in allergic diseases.

PMID- 9236495
TI  - Referred for management of mastocytosis.

PMID- 9236496
TI  - Performance characteristics of a new automated enzyme immunoassay for the
      measurement of allergen-specific IgE. Summary of the probability outcomes
      comparing results of allergen skin testing to results obtained with the HYTEC
      system and CAP system.
AB  - BACKGROUND: Measurement of allergen-specific IgE may assist in the diagnosis of
      allergy in selected patients. The development of new assays for determination of
      allergen-specific IgE should be optimized with respect to analytical sensitivity,
      precision, automation, and reporting of test results in mass units. OBJECTIVE:
      The objectives of this study were to evaluate the analytical performance of the
      new automated HYTEC method for the measurement of allergen-specific IgE and to
      compare the performance of this new assay to that of the Pharmacia CAP system.
      METHODS: To demonstrate parallelism, allergen-specific IgE dilution curves were
      generated by diluting four patient sera containing cat (19.8 kU/L), D.
      pteronyssinus (5.4 kU/L), birch pollen (2.6 kU/L), and timothy grass (1.0 kU/L)
      with equine serum. The precision study utilized sera from three different atopic
      donors with low levels (0.62 +/- 0.05 kU/L), moderate levels (1.45 +/- 0.18
      kU/L), and high levels (13.59 +/- 0.89 kU/L) of allergen-specific IgE to three
      common inhalant allergens: D. pteronyssinus, timothy grass, and birch. Sera for
      outcome probability determinations were obtained from 54 patients who were
      evaluated for the presence of inhalant allergy by skin prick test and physical
      examination. Only sera from patients with at least one positive skin prick test
      that clinically correlate with the physician's evaluation of case history and
      physical examination were selected for study material. In this study, sensitivity
      and specificity are conditional probabilities describing performances of the CAP
      system and the HYTEC system to skin prick testing. The lowest threshold, 0.35
      kU/L, recommended for detection of allergen-specific IgE was used for both
      systems. RESULTS: The HYTEC system accurately detected a reduction in allergen
      specific IgE antibody with different serum concentrations of allergen-specific
      IgE ranging from 0.10 kU/L to 20 kU/L. The median interdilutional coefficient of
      variation of 12.5% was obtained with assay samples containing 19.8 to 0.1 kU/L
      allergen-specific IgE antibody. During a 20-day trial period, three standard
      allergen-specific IgE controls, 0.62, 1.45 and 13.39 kU/L, respectively,
      demonstrated a mean coefficient of variation less than 18%. In 20% of the
      patients, duplicate assay determinations of allergen-specific IgE measurements
      resulted in a one-class discrepancy in the lowest assay range, 0.35 to 0.70 kU/L,
      only. The correlation coefficient between the HYTEC and CAP allergen-specific IgE
      assays was 0.77, rank correlation coefficients, being allergen-dependent and
      ranging from 0.62 to 0.91. Allergen-specific IgE assay sensitivity of the HYTEC
      system ranged from 0.78 to 1.00, whereas the assay sensitivity for the CAP system
      ranged from 0.50 to 1.00. Assay specificity ranged from 0.66 to 0.93 for the
      HYTEC system and from 0.70 to 0.87 for the CAP system. Eighty-nine percent of
      HYTEC-positive patients had a positive skin prick test (3% standard error) and
      87% of CAP-positive patients had a positive skin prick test (4% standard error).
      Ninety-two percent of HYTEC-negative patients had a negative skin prick test (4%
      standard error), whereas 76% of CAP-negative patients had a negative skin prick
      test (5% standard error). CONCLUSION: The HYTEC system fulfills the current
      analytical requirements necessary to measure allergen-specific IgE antibody
      quantitatively and qualitatively, and compares favorably in performance with the
      CAP system.

PMID- 9236497
TI  - Asthma and allergy avoidance knowledge and behavior in postpartum women.
AB  - OBJECTIVE: Based on family history, infants may be classified as "high risk" or
      "low risk" for the development of allergy or asthma. Failure to breast-feed and
      early exposure to cigarette smoke or aeroallergens increase the risk of
      developing asthma or allergy. Since we suspect that physicians seldom educate
      mothers on reducing environmental exposures in the postnatal period, we sought to
      determine the level of maternal knowledge as well as actual avoidance behaviors
      with respect to these risk factors in high risk and low risk families. DESIGN:
      Questionnaire administered by a research assistant. SETTING: Obstetrics unit of
      two tertiary care general hospitals. PATIENTS: A sample of 194 postpartum women
      with uncomplicated pregnancies, interviewed after 24-hours postpartum. MAIN
      OUTCOME MEASURES: (1) Parental history of asthma, allergy or eczema; (2)
      potential for infant exposure to environmental risk factors for asthma and
      allergy, as indicated by history of avoidance practices in the home; (3) parental
      knowledge of risk factors for asthma or allergy; and (4) physician advise on
      avoidance. RESULTS: Of 194 women interviewed, a history of doctor-diagnosed
      asthma, allergy/allergic rhinitis or eczema in either parent was reported by 122
      (high risk group). The remaining 72 patients had no history of atopy (low risk
      group). Of those in the high risk group, 10% of mothers smoked during pregnancy,
      and about 25% were exposed to second hand smoke on a daily basis. Most of the
      mothers in the high risk group planned to breast feed (89%). A large number of
      patients in the high risk group reported potential risk factors for
      allergy/asthma in their home environments. These included animals in the
      household (36%), dusty environments (10%) carpeting (47%), cigarette smoke (18%),
      and others. Despite these risks, only 13% of patients reported being educated by
      their physicians on improving their home environment. Exposures to environmental
      risk factors were not different between low and high risk groups. Similarly,
      knowledge of environmental risk factors and avoidance behaviors were not
      significantly different between low and high risk groups. CONCLUSIONS: Many
      mothers whose infants are at high risk of developing asthma or allergies are not
      aware of and do not practice avoidance of risk factors. Physicians involved in
      prenatal care of women with a family history of atopy and asthma should offer
      advice on reducing exposure to potential risk factors and how to modify their
      environment in ways that can potentially decrease the risk of asthma or allergy
      prevalence and severity.

PMID- 9236498
TI  - Unusual manifestations of hypersensitivity after a tick bite: report of two
      cases.
AB  - BACKGROUND: Ticks are able to transmit, through biting, various viral, parasitic,
      and bacterial diseases, the best known being Lyme disease due to Borrelia
      burgdorferi. In addition, ticks may also induce allergic reactions. OBJECTIVE: A
      study of immediate and delayed skin reactions are undertaken to give evidence of
      an IgE-dependent mechanism. METHODS: Two lumbermen reported having had skin
      reactions following bites by ticks. Skin prick tests and intradermal tests were
      performed with what was most probably Ixodes ricinus extract in one case.
      Specific IgE to whole body extract of wood tick were assayed by radioimmunoassay.
      Histological and immunohistologic examinations of skin biopsy obtained from a
      pruriginous skin lesion and from a delayed reaction following the intradermal
      test, were performed. RESULTS: One of them had positive immediate reactions to a
      prick test and an intradermal test with the same extract. Both patients had
      significant levels of wood tick-specific IgE antibody as well as elevated serum
      total IgE levels. Histologic examinations of a pruriginous lesion revealed
      lymphocytic dermal and perivascular infiltration, with evidence of CD8+ T
      lymphocytes and Langerhans' cells in the perivascular infiltrates. A biopsy of
      the place of the delayed reaction following the intradermal skin test also showed
      the presence of dermal and perivascular lymphocytic infiltrates. CONCLUSION: IgE
      dependent allergy to Ixodes ricinus can explain allergic reactions. Standardized
      extracts have to be prepared with sufficient amounts of the relevant tick
      salivary antigens to permit diagnosis by skin and serologic tests of patients,
      especially lumbermen who may be allergic to Ixodes ricinus.

PMID- 9236499
TI  - Long-term tolerability of nimesulide and acetaminophen in nonsteroidal
      antiinflammatory drug-intolerant patients.
AB  - BACKGROUND: Oral challenges are used to identify alternative nonsteroidal
      antiinflammatory drugs (NSAIDs) for patients who react adversely to drugs of this
      class, but challenge conditions often differ from those in which the drug will
      actually be used. OBJECTIVE: To determine whether the results of oral challenges
      with nimesulide or acetaminophen, using cumulative administration of a single
      therapeutic dose while the patient is in good health, can predict the response to
      multiple doses of the drug during future illness. METHODS: Follow-up interviews
      were conducted with 248 NSAID-intolerant subjects who had tolerated oral
      challenges with nimesulide and/or acetaminophen 1 to 3 years earlier. We analyzed
      the adverse reaction rate in light of the febrile/non-febrile nature of the
      condition treated and the number of doses consumed. RESULTS: Nimesulide was
      tolerated by 115/122 (94.2%) of the patients who had tried it; acetaminophen by
      71/75 (94.6%). A total of 8/159 (5%) patients had experienced reactions (seven
      urticarial and one asthmatic) to one or both drugs. Intolerance was unrelated to
      the nature of the condition treated or the number of doses administered, but all
      four patients who failed to tolerate acetaminophen and 3/7 of those who reacted
      to nimesulide had histories of chronic urticaria. CONCLUSIONS: Oral challenges
      can reliably predict long-term NSAID tolerability in patients with previous
      adverse reactions to other drugs of this class, except for patients with chronic
      urticaria.

PMID- 9236500
TI  - Dose ranging study of mometasone furoate (Nasonex) in seasonal allergic rhinitis.
AB  - BACKGROUND: Topical nasal corticosteroids are rapidly gaining acceptance as first
      line therapy for seasonal allergic rhinitis, but there is a desire for effective
      corticosteroids with an improved safety profile over existing products.
      OBJECTIVE: A multicenter, double-blind dose ranging study was conducted to
      compare the activity and tolerance of four doses of mometasone furoate nasal
      spray (tradename Nasonex) and placebo in adult patients with seasonal allergic
      rhinitis. METHODS: Four hundred eighty patients with seasonal allergic rhinitis
      were enrolled and randomized to receive mometasone furoate nasal spray 50
      micrograms (n = 96), 100 micrograms (n = 95), 200 micrograms (n = 98) or 800
      micrograms (n = 95), or placebo vehicle (n = 95) once daily for 28 days. RESULTS:
      All of the doses of mometasone furoate nasal spray showed activity in reducing
      the severity of rhinitis. The 200-microgram dose reduced total nasal symptom
      scores and total symptom scores throughout the study (P < .05 versus placebo
      vehicle). The 50-microgram dose and the 100-microgram dose showed less consistent
      activity at early timepoints (days 3 and 7), while the 800 microgram dose did not
      provide significant additional benefits over the 200-microgram dose. All dose
      levels were well tolerated CONCLUSION: The results of this trial indicate that
      200 micrograms once daily is the optimum dose of mometasone furoate nasal spray
      for the treatment of seasonal allergic rhinitis.

PMID- 9236501
TI  - Yearly and seasonal changes of specific IgE to japanese cedar pollen in a young
      population.
AB  - BACKGROUND: There have been no detailed long-term observations of the
      relationship between specific IgE production and stimulation by various naturally
      occurring allergens. OBJECTIVE: This study was conducted to elucidate the yearly
      and seasonal changes of specific IgE antibody production to Japanese cedar
      pollen, an allergen of Japanese cedar pollinosis, in young adults. METHODS: The
      number of Japanese cedar pollen were counted over a period of 9 years. Changes in
      the percentages of antibody carriers to Japanese cedar pollen and mite were
      examined during these years. Changes in Japanese cedar pollen-specific IgE levels
      between a low exposure year and a high exposure year in individual subjects were
      also investigated. RESULTS: From 1987 to 1995, the percentages of Japanese cedar
      pollen-IgE carriers varied from about 30% to 50% with the intensity of pollen
      stimulation, and carriers tended to increase yearly. The rates of anti-mite IgE
      carriers changed little. In the spring which is the pollen season, Japanese cedar
      pollen-IgE levels in low exposure years were weaker than those in high exposure
      years in individual subjects. Levels in autumn, which is not the pollen season,
      showed equivalent levels in both high and low exposure years. Anti-mite IgE
      levels in individual subjects varied little during these years. CONCLUSIONS: A
      long-term follow-up study supported that Japanese cedar pollen-IgE production is
      mainly associated with the degree of allergen exposure.

PMID- 9236502
TI  - Effect of cow milk on pulmonary function in atopic asthmatic patients.
AB  - BACKGROUND: There is a perception by some asthmatic patients that stimulation of
      respiratory mucous production by cow milk may worsen airway obstruction.
      OBJECTIVE: To determine whether cow milk ingestion reduces bronchial airflow in
      asthmatic patients as measured by standard spirometry. METHODS: Twenty-five
      atopic adults with mild asthma but no history of cow milk allergy or lactose
      intolerance participated in a prospective, randomized, double-blind, placebo
      controlled crossover study. Subjects were randomly assigned to ingest either a
      solution containing cow milk powder or a placebo solution, received neither
      during a 14-day washout period, then ingested the alternate solution. Forced
      vital capacity (FVC), forced expiratory volume in 1 second (s) (FEV1), and
      FEV1/FVC were measured at 30 minutes, 1 hour (h), and 7 hours after challenge. A
      > or = 20% decrease in FEV1 or FEV1/FVC was considered clinically significant.
      RESULTS: FEV1 was slightly lower at 30 minutes than the baseline value (mean
      change, .6% to 3.3%) for both challenges. None of the subjects experienced any
      adverse symptoms, acute or delayed, after cow milk or placebo challenges.
      Statistically significant changes in FEV1 were reached 30 minutes after cow milk
      challenge (P = .0007) and at one hour after placebo (P = .0027). These changes
      are not clinically significant. CONCLUSION: Although this study disclosed no
      acute or delayed asthmatic symptoms or deterioration of pulmonary function
      detected by using conventional spirometry, methacholine inhalation before and
      after cow milk challenge may be more sensitive for evaluation of cow milk-induced
      bronchial hyperreactivity.

PMID- 9236503
TI  - Epigallocatechin gallate-induced histamine release in patients with green tea
      induced asthma.
AB  - BACKGROUND AND OBJECTIVE: Epigallocatechin gallate is the causative agent of
      green tea-induced asthma. To determine whether an IgE-mediated mechanism plays a
      pathogenetic role in this disorder, we measured histamine release after in vitro
      exposure to epigallocatechin gallate. METHODS: Subjects included eight patients
      (four men and four women) with green tea-induced asthma, who had been diagnosed
      by skin test and inhalation challenge, and eight controls (four asthmatic
      subjects with no previous exposure tea dust and four healthy volunteers).
      Heparinized whole blood samples were taken and incubated with epigallocatechin
      gallate at various concentrations (final concentration range, 0.003 to 300
      micrograms/mL) for 30 minutes at 37 degrees C. After centrifugation, histamine
      was measured in the cell-free supernatants by radioimmunoassay. Histamine release
      was expressed as a percentage of total histamine. A result higher than 10% was
      considered positive. RESULTS: In one of the tea-sensitive patients,
      epigallocatechin gallate did not cause histamine release. Five of the other seven
      patients (71%) demonstrated a positive, dose-dependent histamine release to
      epigallocatechin gallate. In asthmatic and normal controls, histamine release was
      not observed at any epigallocatechin gallate concentration. Furthermore, a
      significant correlation was noted between the maximum percentage histamine
      release and the threshold epigallocatechin gallate concentration for intradermal
      skin testing. CONCLUSION: These results indicate that an IgE-mediated response is
      the basis for green tea-induced asthma.

PMID- 9236504
TI  - Improvement of bronchial hyperresponsiveness in asthmatic children treated for
      concomitant sinusitis.
AB  - BACKGROUND: There appears to be an association between sinusitis and asthma. The
      effect on bronchial hyperresponsiveness of clinical therapy for sinusitis in
      children may help to decipher whether sinusitis and asthma are independent
      manifestations of the same disease. OBJECTIVE: To evaluate the effect of clinical
      treatment for sinusitis in patients with rhinitis and/or asthma on symptoms and
      on bronchial hyperresponsiveness to methacholine. METHODS: Open label,
      randomized, non-treatment control in a teaching hospital in Sao Paulo, Brazil.
      Forty-six atopic and 20 normal children were studied. The atopic children
      consisted of 18 with allergic rhinitis (12 without sinusitis and 6 with
      sinusitis), and 28 children with rhinitis with asthma (13 with normal sinus
      radiographs and 15 with complete opacification of the maxillary sinuses).
      Methacholine PC20 was determined before and 30 days after treatment with nasal
      saline, sulfamethoxazole-trimethoprim, antihistamine/decongestant, and five days
      of prednisone. Sinus radiographs were also repeated. RESULTS: The only patients
      with increase in methacholine PC20 were patients with rhinitis and asthma with
      opacified maxillary sinuses at entry and who at 30 days had normal sinus
      radiographs (P < .05). CONCLUSION: In this study, children with allergic rhinitis
      and sinusitis with asthma improved their bronchial hyperresponsiveness to
      methacholine and decreased their symptoms with appropriate response of their
      sinuses to clinical therapy.

PMID- 9236505
TI  - Identification of IgE-binding components in occupational asthma caused by corn
      dust.
AB  - BACKGROUND: There have been some reports of corn dust-induced occupational asthma
      that suggest nonimmunologic mechanism. In this paper, we present a case of
      occupational asthma and rhinitis caused by corn dust where bronchoconstriction
      was induced by an IgE-mediated reaction. METHODS AND RESULTS: The patient had
      positive responses to weed and grass pollens as well as corn dust extracts. The
      bronchoprovocation test elicited an early asthmatic response to corn dust
      extracts. Serum-specific IgE and IgG4 antibodies to corn dust extracts were
      detected by enzyme-linked immunosorbent assay (ELISA). In order to identify
      further the allergenic component of the extracts, sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting studies were
      performed. Ten IgE-binding components (9 to 140 kD) were detected within the corn
      dust extracts. CONCLUSION: These results suggest that inhalation of corn dust can
      cause IgE-mediated bronchoconstriction in an exposed worker.

PMID- 9236506
TI  - Prevalence of asthma and wheezing in public schoolchildren: association with
      maternal smoking during pregnancy.
AB  - BACKGROUND: Asthma is the most common chronic disease in childhood. The
      prevalence of asthma is especially high in inner city children. The occurrence of
      asthma may be associated with many environmental factors, including involuntary
      exposure to maternal smoking. OBJECTIVES: This study reports prevalence of asthma
      and wheezing in a sample of public school students in Chicago and examines the
      association between maternal smoking during pregnancy and childhood asthma.
      METHODS: A total of 705 fifth grade students from 13 public schools participated
      in the study. A slightly modified International Study of Asthma and Allergies in
      Childhood (ISAAC) questionnaire was administered in classrooms to assess
      students' wheezing and asthma prevalence. RESULTS: Overall, 34.5% of children
      reported ever wheezing, 28.9% reported wheezing in the past year, 21.1% reported
      exercise-related wheezing in the past year, 23.6% reported physician-diagnosed
      asthma, 16.1% reported taking asthma or wheezing medication in the past 2 weeks,
      and 15.2% reported visiting emergency rooms for treatment of asthma in the past
      year. After adjusting for confounding variables in a logistic model, maternal
      smoking during pregnancy was significantly associated with children's asthma
      (adjusted odds ratio = 1.9; 95% confidence interval: 1.1 to 3.5). CONCLUSIONS:
      This study reports high prevalence of asthma and wheezing among the students and
      suggests that maternal smoking during pregnancy may increase the risk of asthma
      in children.

PMID- 9236507
TI  - Proventil HFA provides protection from exercise-induced bronchoconstriction
      comparable to proventil and ventolin.
AB  - INTRODUCTION: During the 1970s, scientists suggested that the growing use of
      chlorofluorocarbons (CFCs) was contributing to depletion of the stratospheric
      ozone layer with potentially harmful results. A committee on the ozone layer
      organized the preparation of the Montreal Protocol. This protocol mandated the
      cessation of production and use of CFCs by January 1, 1996. The primary exemption
      to this ban is for the use of CFCs as propellants in metered dose inhalers (MDIs)
      for the treatment of asthma. Suitable replacement hydrofluoroalkane (HFA)
      propellants, such as HFA-134a, for use in MDIs have been identified. Albuterol, a
      selective beta-adrenergic agonist, currently widely available for inhalation
      asthma therapy, has been reformulated in HFA-134a (Proventil HFA). OBJECTIVE; To
      compare the efficacy of Proventil HFA to Ventolin, Proventil, and placebo (HFA
      134a) MDI in protecting asthmatic patients from exercise-induced
      bronchoconstriction. METHODS: This was a randomized, single-blind, placebo
      controlled, 4-period crossover study of asthmatic patients with documented
      exercise-induced broncho-constriction. Twenty patients self administered two
      puffs of either Proventil HFA, Ventolin, Proventil or placebo, from an MDI, 30
      minutes prior to performing a standardized exercise challenge at the study site.
      Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes
      after completion of the exercise challenge. Heart rate and blood pressure were
      measured just prior to spirometry and a 12-lead ECG was performed 15 minutes
      after completion of the exercise challenge for measurement of the QT corrected
      interval. RESULTS: The primary efficacy variable was the smallest percent change
      from the predose FEV1 following exercise. The smallest percent change from
      predose FEV1 for Proventil HFA was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD
      for Ventolin, and the 3.6 +/- 10.2 SD for Proventil. The smallest percent change
      from predose FEV1 for each of the active treatments was significantly different
      from placebo, -23.7 +/- 14.5. Twelve of the patients had a > or = 20% fall in
      FEV1 post-exercise with placebo pretreatment, but only 1, 1, and 0 had > or = 20%
      FEV1 falls after treatment with Proventil HFA, Ventolin, and Proventil
      respectively. Changes in heart rate, blood pressure and QT corrected interval
      were similar for the three active treatments following exercise. CONCLUSIONS:
      Proventil HFA provides protection against exercise-induced bronchoconstriction
      comparable to Ventolin and Proventil and protection superior to placebo.
      Proventil HFA has a safety profile similar to Ventolin when used to prevent
      exercise-induced bronchoconstriction.

PMID- 9236508
TI  - Acute leukemias express a functional receptor for the human growth hormone.
AB  - The potential influence of the human growth hormone (hGH) on the behavior of
      acute leukemias is a matter of controversy. We investigated primary childhood and
      adult leukemias (n = 44) and leukemic cell lines (n = 13) for the expression of
      the hGH receptor (hGHR) by immunohistochemistry and flow cytometry. All leukemias
      expressed the hGHR in the cytoplasm; expression on the surface was undetectable
      in some of the leukemias. In leukemic cell lines, hGHR expression on the surface
      was demonstrated in a dose-dependent manner after incubation with rhGH.
      Physiologic concentrations of hGH were more efficient than higher doses in
      increasing hGHR surface expression. A proliferative response to hGH was
      accomplished in cell lines REH, Molt4, and K562. However, only one of 19 primary
      leukemias (ALL, n = 12; AML, n = 7) showed increased cell counts after the
      addition of 50-800 ng/ml recombinant hGH (rhGH). These cells were of an immature
      T-cell phenotype. We thus conclude that acute leukemias can be stimulated by hGH
      to up-regulate its receptor, but that most primary leukemias may require
      additional signals for the induction of proliferation.

PMID- 9236509
TI  - A statistically significant sex difference in the number of colony-forming cells
      from human peripheral blood.
AB  - The number of colony-forming cells (CFC) in the peripheral blood (PB) of 43
      volunteers was examined using a semisolid clonogenic culture assay. In all, 22
      male (age 21-39 years) and 21 female individuals (age 21-39 years) were tested,
      ten of each group twice to examine the intraindividual variability of colony
      forming cells in PB. A statistically significant sex difference in the number of
      CFC, erythroblastic colonies (BFU-E), and granulocyte/macrophage colonies (CFU
      GM) in PB was detected in favor of male individuals. No significant difference
      between female and male PB was found for the number of CFU-GEMM. The
      intraindividual variability of CFC and BFU-E was significantly higher in female
      donors. These results support previous reports by others on a potential influence
      of sex steroids on hematopoiesis.

PMID- 9236510
TI  - Severe bleeding in two patients due to increased sensitivity of factor IX
      activity to phenprocoumon therapy.
AB  - Two male patients with severe and recurrent bleeding episodes under phenprocoumon
      therapy are reported. Both patients exhibited a strong decrease of their factor
      IX activities below 1% of normal, whereas the activities of the vitamin K
      dependent factors prothrombin, VII, and X were found to be within or above the
      expected therapeutic ranges of 20-40%. Upon removal of phenprocoumon and
      substitution with vitamin K, the factor IX activities increased to 85% and 55%,
      respectively. Reexposition to phenprocoumon in one patient confirmed the rapid
      and selective decrease of the factor IX activity. These findings provide the
      first report of an abnormally high sensitivity of factor IX activity to oral
      anticoagulant therapy.

PMID- 9236511
TI  - Evaluation of bone marrow iron by magnetic resonance imaging.
AB  - Bone marrow iron was estimated by magnetic resonance imaging (MRI) using spin
      echo sequences with multiple echoes in 22 patients with varying degrees of tissue
      storage iron. Levels of bone marrow iron concentration (BMIC) were determined
      chemically in biopsied specimens concurrently. Concentrations of serum iron,
      serum ferritin, and transferrin saturation were also measured to evaluate body
      iron status. Significant correlation was observed between BMIC and T2 relaxation
      rate (1/T2) (r = 0.77; p < 0.001) in all patients with BMIC levels below 400
      micrograms/ml, while BMIC was not correlated with T2 in patients with extremely
      high BMIC levels. MRI was considered to be inappropriate for quantitation of 1/T2
      in patients with extremely high BMIC due to an extreme shortening of T2
      relaxation time. These observations suggest that MRI may be a useful and
      noninvasive method for systemic quantitative determination of bone marrow iron.

PMID- 9236512
TI  - Induction of a hematological and cytogenetic remission in a patient with a
      myelodysplastic syndrome secondary to Fanconi's anemia employing the S-HAM
      regimen.
AB  - We report on a patient with Fanconi's anemia (FA) who developed a myelodysplastic
      syndrome (RAEB-T) with complex karyotypic abnormalities (trp 1q23q42, monosomy
      20, trisomy 13) at the age of 28. The patient achieved a complete hematological
      and cytogenetic remission after treatment with sequential high-dose cytosine
      arabinoside/mitoxantrone followed by G-CSF (5 micrograms/kg). Bone marrow
      hypoplasia was prolonged with 38 days of granulocytopenia < 500/microliters and
      62 days of platelet transfusion dependency. Nonhematological toxicity did not
      exceed that of patients without underlying FA. Remission duration was 7 months.
      This observation shows the feasibility of high-dose Ara C treatment in patients
      with FA and MDS. Although hematopoiesis remained clonal in remission, the
      suppression of the cytogenetically abnormal clones transiently reversed the
      antecedent long-lasting pancytopenia.

PMID- 9236513
TI  - Response of the extramedullary lung plasmacytoma with pleural effusion to
      chemotherapy.
AB  - An elderly patient with extramedullary lung plasmacytoma and subsequent pleural
      effusion is described. The presence of abnormal plasma cells in the pleural fluid
      led to diagnosis. Histologically similar conditions such as multiple myeloma and
      solitary myeloma of bone were ruled out by clinical evaluation. These neoplasms
      usually occur in the head and neck area and are not characterized by paraprotein
      accumulation. Few cases in the lung have been reported. We describe a case of
      extramedullary plasmacytoma of the lung with plasmacytoma-induced pleural
      effusion and the presence of monoclonal paraprotein in both the serum and urine.
      Chemotherapy with melphalan was effective in reducing the size of the
      plasmacytoma, and pleurodesis was used to manage the pleural effusion.

PMID- 9236514
TI  - Documented sudden onset of pseudothrombocytopenia.
AB  - A 66-year-old male patient was hospitalized for severe heart failure. Within 3
      days after admission his platelet count dropped from 148 x 10(9)/l to 3 x
      10(9)/l. Pseudothrombocytopenia was diagnosed based on the platelet count of 3 x
      10(9)/l in K3-EDTA anticoagulated blood as opposed to 110 x 10(9)/l in sodium
      citrate. Platelet reactive antibodies were not detectable. To the best of our
      knowledge, this is the first report of a documented onset of
      pseudothrombocytopenia.

PMID- 9236515
TI  - Gilbert's syndrome co-existing with and masking hereditary spherocytosis.
AB  - An unusual case of co-existing Gilbert's syndrome and hereditary spherocytosis is
      reported. Diagnostic strategies are presented, and the literature is reviewed for
      simultaneous presence of these disorders.

PMID- 9236516
TI  - Chronic lymphocytic leukemia and hairy-cell leukemia--diagnosis and treatment:
      results of a consensus meeting of the German CLL Cooperative Group.

PMID- 9236517
TI  - Acute pancreatitis after all-trans retinoic acid therapy.

PMID- 9236518
TI  - Topically applied bovine collagen in the treatment of ulcerative necrobiosis
      lipoidica diabeticorum.

PMID- 9236519
TI  - Transdermal nicotine suppresses cutaneous inflammation.
AB  - BACKGROUND: Cigarette smoking significantly alters the inflammatory response in
      the skin following application of irritants and rubefacients. The mechanism of
      this effect is unknown. There are thousands of components in cigarette smoke that
      may be pharmacologically important, but there is evidence to suggest that
      nicotine may play an important role in the observed effect on the inflammatory
      process. DESIGN: This was an interventional study to assess cutaneous
      responsiveness to different stimuli after transdermal nicotine administration in
      volunteer subjects. Cutaneous testing was performed at baseline and at weeks 2
      and 4 (the end) of the study. SETTING: The department of Dermatology, University
      Hospital of Wales, Cardiff. PARTICIPANTS: Ten lifelong nonsmokers were recruited
      for the study. INTERVENTION: Nicotine patches were applied daily for 1 month.
      MAIN OUTCOME MEASURES: The following tests were performed: application of 2 times
      the minimal irritancy dose of sodium lauryl sulfate, irradiation with 2 times the
      minimal erythema dose of UV-B, measurement of cutaneous vasodilation following
      application of ethyl and hexyl nicotinate, and reactive hyperemia following
      arterial occlusion. RESULTS: There was a significant reduction in the cutaneous
      inflammatory response to sodium lauryl sulfate (P < .001) and irradiation with UV
      B (P < .003) and a reduction in reactive hyperemia (P < .03) after 2 weeks of
      treatment, which returned values to normal at 4 weeks. There was no change in
      blood flow following application of topical nicotinates. CONCLUSIONS: Nicotine
      administration via a transdermal delivery system suppresses the cutaneous
      inflammatory response to sodium lauryl sulfate and UV-B, as well as triggers a
      transient suppression of reactive hyperemia following arterial occlusion. The
      apparent anti-inflammatory effects of smoking cigarettes can therefore only
      partially be explained as a long-term effect of nicotine.

PMID- 9236520
TI  - Apoptotic and proliferating cells in cutaneous lymphoproliferative diseases.
AB  - BACKGROUND: The cell production vs the cell loss rate in one of the most
      important parameters in evaluating growth and biological behavior of neoplasms.
      Individual cell disintegration in tissues, apoptosis, is a constant finding in
      various tumors and has been shown, by using several techniques, as a recognizable
      cell death that is different from necrosis. DESIGN: We studied the apoptosis
      proliferation ratio in various lymphoproliferative disorders in the skin,
      including mycosis fungoides (MF), cutaneous T-cell lymphoma showing solid tumor
      mass (CTCL), B-cell lymphoma of the skin (BCL), lymphomatoid papulosis (LyP), and
      cutaneous pseudolymphoma by using terminal deoxyuridine triphosphate (dUTP)
      biotin nick end labeling (TUNEL), a newly developed method to detect
      internucleosomal breaks characteristic of apoptotic cells. SETTING: University
      referral center. PATIENTS: Fifty patients with cutaneous lymphoproliferative
      diseases. MAIN OUTCOME MEASURES: Proliferation indexes and apoptosis index
      calculated by using immunohistochemical techniques. RESULTS: The proliferation
      indexes in pseudolymphoma, which were calculated by using immunohistochemical
      analyses with anti-proliferating cell nuclear antigen and anti-MIB-1 monoclonal
      antibodies, were significantly lower than the indexes of MF, CTCL, BCL, and LyP,
      whereas, the apoptosis index in Lyp was significantly higher than in any other
      lymphoproliferative diseases studied. The apoptosis-proliferation ratio in the
      tumor stage of MF, CTCL, and BCL was almost constant, but the ratios in LyP and
      the plaque stage of MF were significantly higher than in the other diseases
      studied. CONCLUSIONS: The clinical behavior of each lymphoproliferative disease
      in the skin seemed to be reflected in the apoptosis and proliferation indexes. We
      conclude that these indexes may become useful factors in the determination of the
      diagnosis and the prognosis for patients with lymphoproliferative diseases.

PMID- 9236521
TI  - Keratinocyte-lymphocyte interaction in cutaneous T-cell lymphoma. Modulation of
      keratinocyte antigen My7 by a soluble factor produced by T lymphocytes.
AB  - OBJECTIVE: To test the hypothesis that the modulation of My7 antigen in the basal
      keratinocytes is directly related to the effect of dermal lymphocyte infiltrate
      of epidermotropic cutaneous T-cell lymphoma (CTCL). DESIGN: In vitro study with
      reconstituted skin model. SETTING: Department of Dermatology of University
      Hospital, Nantes, France. PATIENTS: Lymphocytes extracted from 11 skin samples
      with lesions of epidermotropic CTCL (mycosis fungoides, stages IIa to IV) and 6
      skin samples with lesions of atopic dermatitis (control population) together with
      the supernatants of these infiltrating lymphocytes were incubated with normal
      reconstituted skin samples either alone or in the presence of interferon alfa-2a
      (10(2) IU/ mL). Moreover, normal peripheral blood mononuclear cells of 7 patients
      and 4 controls were incubated with reconstituted skin. INTERVENTION: None MAIN
      OUTCOME MEASURES: None. RESULTS: Ten of 11 samples of lymphocytes extracted from
      CTCL and 7 of 11 of their supernatants inhibited partially or completely My7
      expression by basal cells. NO inhibition was noted for lymphocytes extracted from
      inflammatory skin or their supernatants. Addition of interferon alfa-2a in a
      culture medium of extracted lymphocytes or their supernatants blocked inhibition
      of My7 expression by keratinocytes in 8 of 10 reconstituted skin samples. No
      abrogation of My7 expression was noted with peripheral mononuclear cells.
      CONCLUSIONS: Our in vitro study demonstrated a direct and specific interaction
      between the tumor infiltrate of CTCL and keratinocytes. Moreover, this
      interaction appeared to be closely associated with a soluble factor produced by
      the tumor T-cell infiltrate and was at least partially blocked by interferon alfa
      2a.

PMID- 9236522
TI  - Epidermal apoptotic cell death in erythema multiforme and Stevens-Johnson
      syndrome. Contribution of perforin-positive cell infiltration.
AB  - OBJECTIVE: To clarify the mechanism of epidermal cell death in erythema
      multiforme. DESIGN: Retrospective study. SETTING: Academic referral center.
      PARTICIPANTS: Nine patients with Stevens-Johnson syndrome (SJS), 9 patients with
      Hebra disease (EMH), and 5 healthy volunteers. INTERVENTIONS: Biopsy specimens
      were obtained from the border of the fresh lesions before treatment. Control
      specimens were obtained from normal skin. MAIN OUTCOME MEASURES:
      Histopathological epidermal apoptosis detected with nuclear DNA fragmentation and
      counts of dermal immunoreactive perforin-positive infiltrates were compared
      between SJS and EMH. RESULTS: Eight patients (89%) with SJS showed clear
      apoptosis with keratinocyte DNA fragmentation. All SJS samples had intensive
      perforin-positive dermal infiltrates. Only 3 patients (33%) with EMH showed
      apoptotic change, and it was to a far less extent with far less dermal perforin
      positive infiltrates. Control specimens showed no apoptotic cells in the
      epidermis or expression of perforin in the dermis. CONCLUSIONS: Perforin mediates
      apoptosis in the pathogenesis of the epidermal cell changes in SJS but not in
      EMH. In addition to the differences in clinical severity and histopathological
      conditions, our findings indicate a pathogenic difference between SJS and EMH.

PMID- 9236523
TI  - Multiple facial angiofibromas and collagenomas in patients with multiple
      endocrine neoplasia type 1.
AB  - OBJECTIVES: To evaluate patients with multiple endocrine neoplasia type 1 (MEN 1)
      for cutaneous manifestations. DESIGN: Survey during a 3-year period. SETTING: The
      National Institutes of Health, a tertiary referral research hospital in Bethesda
      Md. PATIENTS: A consecutive sample of 32 individuals with previously diagnosed
      MEN1 who were not preselected for the presence of skin lesions were examined for
      cutaneous abnormalities. None of the patients or family members were diagnosed as
      having tuberous sclerosis. INTERVENTIONS: Lesions were identified by clinical
      appearance, photographed, and confirmed histologically. MAIN OUTCOME MEASURE: To
      determine the frequency of skin lesions in patients with MEN1. RESULTS: Multiple
      facial angiofibromas were observed in 28 (88%) of the patients with MEN1, with 16
      patients (50%) having 5 or more. Angiofibromas were clinically and histologically
      identical to those in individuals with tuberous sclerosis. Collagenomas were
      observed in 23 patients (72%). Also observed were cafe au lait macules in 12
      patients (38%), lipomas in 11 patients (34%), confetti-like hypopigmented macules
      in 2 patients (6%), and multiple gingival papules in 2 patients (6%).
      CONCLUSIONS: Multiple angiofibromas, collagenomas, lipomas, confetti-like
      hypopigmented macules and multiple gingival papules are cutaneous manifestations
      of MEN1 and should be looked for in both family members of patients with MEN1 and
      individuals with hyperparathyroidism of other MEN1-associated tumors. Multiple
      angiofibromas can no longer be considered pathognomonic for tuberous sclerosis.
      The observation of angiofibromas in individuals without tuberous sclerosis
      necessitates further biochemical testing for MEN1.

PMID- 9236524
TI  - Self-application of a protective cream. Pitfalls of occupational skin protection.
AB  - OBJECTIVES: To determine if a protective cream (PC) is adequately applied to the
      hands by workers in several occupations and to quantify what areas are covered or
      missed. DESIGN: Prospective diagnostic study. SETTINGS: Metalworking factory,
      construction sites, and university hospital. PARTICIPANTS: One hundred fifty
      healthy volunteers (50 from each setting) were recruited for a questionnaire
      interview and typical self-application of a PC. INTERVENTION: None. MAIN OUTCOME
      MEASURE: Percentage of sufficient cover with PC as assessed with fluorescence
      under Wood light. RESULTS: Many areas were skipped when viewed under Wood light.
      The application of PC was incomplete, especially on the dorsal aspects of the
      hands. CONCLUSION: Individuals should be made aware of the most commonly missed
      regions to ensure complete skin protection. This simple method is a useful
      adjunct to quantify self-application and in worker education.

PMID- 9236525
TI  - Epstein-Barr virus-associated lymphoproliferative disease during methotrexate
      therapy for psoriasis.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-associated lymphoproliferative disorders
      have recently been observed during treatment of rheumatoid arthritis and
      dermatomyositis with low-dose methotrexate. OBSERVATION: A patient with psoriasis
      developed a B-cell lymphoproliferative disorder during long-term treatment with
      low-dose methotrexate. The lymphoid cells expressed EBV latent membrane protein
      1, and the EBV viral genome was present as demonstrated by in situ hybridization.
      Evaluation for EBV clonality showed that the lymph node contained clonal EBV DNA.
      Polymerase chain reaction studies confirmed that the B-cell lymphoproliferative
      disorder was mainly monoclonal, suggesting that the disorder arose from a single
      EBV-infected B-cell clone. CONCLUSIONS: Lymphoproliferative disorders associated
      with Epstein-Barr virus in which the clinicopathological presentation is similar
      to those occurring in patients after transplantation may be observed in patients
      with psoriasis treated with methotrexate. While it is impossible to rule out a
      fortuitous occurrence of an EBV-associated lymphoproliferative disorder and
      psoriasis treated with methotrexate in the same patient, EBV appears to be
      critical in the pathogenesis of the lymphoproliferative disorder in this patient.

PMID- 9236526
TI  - Chemotherapy-induced eccrine squamous syringometaplasia. A distinctive eruption
      in patients receiving hematopoietic progenitor cells.
AB  - BACKGROUND: Eccrine squamous syringometaplasia (ESS) has been associated with
      characteristic clinical eruption in patients receiving chemotherapy. It has been
      suggested as a diagnostic clue in the diagnosis of chemotherapy-induced reactions
      vs acute graft-vs-host disease, as well as other drug reactions. We identified 10
      cases of ESS in patients in whom a distinctive clinical eruption developed during
      or after a pretransplantation conditioning regimen with high-dose chemotherapy. A
      complete clinical and histologic evaluation was performed in all patients.
      OBSERVATIONS: All patients developed erythematous and edematous plaques or
      confluent erythematous macular areas in the axillae and/or groin, with painful
      areas of well-defined erythema and edema on palms and/or soles in 5 patients.
      Some discrete papular lesions on the trunk or extremities could also be observed
      in most patients. The histologic hallmark of the eruption was ESS, with a
      variable degree of cornification and apoptosis. A vacuolar interface dermatitis
      and a variable degree of cellular atypica were also consistent findings.
      CONCLUSIONS: Chemotherapy-induced ESS may be associated with a distinctive
      clinical eruption and should be considered in the differential diagnosis of
      erythematous eruptions during or after a pretransplantation conditioning regimen
      with high-dose chemotherapy.

PMID- 9236527
TI  - Cutaneous involvement in sarcoidosis. Relationship to systemic disease.
AB  - Sarcoidosis is an antigen-mediated disease defined by granuloma formation in
      different organs. It involves mainly the mediastinal and peripheral lymph nodes,
      lungs, eyes, skin, liver, and spleen. Cutaneous lesions of sarcoidosis may be
      specific, showing histologically noncaseating granulomas, or nonspecific, most
      typically erythema nodosum. Frequently, both types of skin lesions are the means
      of presentation of the disease and may contribute to the diagnosis. A workup for
      systemic sarcoidosis should be undertaken in every patient with sarcoid cutaneous
      granulomas. Some types of cutaneous lesions have prognostic significance. Lupus
      pernio and plaques are associated with more severe systemic involvement and more
      chronic course, while erythema nodosum is the hallmark of acute and benign
      disease.

PMID- 9236528
TI  - Dermatologic drugs, pregnancy, and lactation. A conservative guide.
AB  - No database for determination of precise risk of drug use during pregnancy and
      lactation is available. There are, however, educated opinions concerning the
      advisability of use of a drug during the childbearing years from manufacturers,
      the Food and Drug Administration, various teratologists, the American Academy of
      Pediatrics, and the World Health Organization. Not all medications are absolutely
      contraindicated during pregnancy and lactation. Some drugs have been extensively
      used without apparent adverse effects in the mother or infant. When it is
      necessary to select a medication for use during pregnancy or lactation, the
      medication should have minimal risk. This article summarizes dermatologic drugs
      whose known risk is low.

PMID- 9236529
TI  - Cigarette smoking and inflammatory skin disease. The good and the bad.

PMID- 9236530
TI  - Lymphomas during long-term methotrexate therapy.

PMID- 9236531
TI  - Antineoplastic chemotherapy, sweat, and the skin.

PMID- 9236532
TI  - A persistent periorificial eruption. Necrolytic migratory erythema (NME)
      (glucagonoma).

PMID- 9236533
TI  - A solitary warty plaque. Isolated cerebriform collagenoma.

PMID- 9236534
TI  - Multiple asymptomatic hyperkeratotic papules on the lower part of the legs.
      Hyperkeratosis lenticularis perstans (HLP) (Flegel disease).

PMID- 9236535
TI  - Nonhealing ulcers on the lower extremities. Cryoglobulinemia.

PMID- 9236536
TI  - Fibroepithelial polyps and pathologic evaluation.

PMID- 9236537
TI  - BCG vaccination and interpretation of purified protein derivative test results.

PMID- 9236538
TI  - Efficacy and tolerance of liposomal daunorubicin in Kaposi sarcoma associated
      with human immunodeficiency virus infection.

PMID- 9236540
TI  - Pulsed dye laser treatment of angiolymphoid hyperplasia with eosinophilia
      lesions.

PMID- 9236539
TI  - Sequences of human herpesvirus 8 are not detected in various non-Kaposi sarcoma
      vascular lesions.

PMID- 9236541
TI  - Videomicroscopy predicts outcome in treatment of port-wine stains.

PMID- 9236542
TI  - Comparison of computer-aided design and rule of nines methods in the evaluation
      of the extent of body involvement in cutaneous lesions.

PMID- 9236544
TI  - Molecular biology of behavior. Targets for therapeutics.

PMID- 9236543
TI  - A molecular and cellular theory of depression.
AB  - Recent studies have begun to characterize the actions of stress and
      antidepressant treatments beyond the neurotransmitter and receptor level. This
      work has demonstrated that long-term antidepressant treatments result in the
      sustained activation of the cyclic adenosine 3',5'-monophosphate system in
      specific brain regions, including the increased function and expression of the
      transcription factor cyclic adenosine monophosphate response element-binding
      protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the
      regulation of specific target genes, including the increased expression of brain
      derived neurotrophic factor in certain populations of neurons in the hippocampus
      and cerebral cortex. The importance of these changes is highlighted by the
      discovery that stress can decrease the expression of brain-derived neurotrophic
      factor and lead to atrophy of these same populations of stress-vulnerable
      hippocampal neurons. The possibility that the decreased size and impaired
      function of these neurons may be involved in depression is supported by recent
      clinical imaging studies, which demonstrate a decreased volume of certain brain
      structures. These findings constitute the framework for an updated molecular and
      cellular hypothesis of depression, which posits that stress-induced vulnerability
      and the therapeutic action of antidepressant treatments occur via intracellular
      mechanisms that decrease or increase, respectively, neurotrophic factors
      necessary for the survival and function of particular neurons. This hypothesis
      also explains how stress and other types of neuronal insult can lead to
      depression in vulnerable individuals and it outlines novel targets for the
      rational design of fundamentally new therapeutic agents.

PMID- 9236545
TI  - A controlled family history study of childhood-onset depressive disorder.
AB  - BACKGROUND: We studied the family psychiatric history of 125 youths with
      childhood-onset depressive disorder (a portion of whom developed bipolar
      disorder) and 55 psychiatric controls with nonaffective disorder. METHODS:
      Probands were classified according to prospectively observed clinical course in
      childhood. Family psychiatric history was determined by interviewers blind to
      probands' diagnosis, with mothers typically informing about themselves and about
      remaining first- and a all second-degree adult relatives. RESULTS: Families of
      affectively ill juveniles had 5-fold greater odds of lifetime depressive disorder
      and 2-fold greater odds of recurrent unipolar depressive disorder than did
      families of psychiatric controls. The higher risk of depression was most evident
      in first-degree and female relatives. Mothers of affectively ill youths were
      younger at onset of depression than were mothers of controls. Alcoholism and
      substance use disorders were more prevalent in relatives of affectively ill
      probands than in controls and cosegregated with familial depression. However,
      other covariates were more important at predicting patterns of familial
      depression. Familial illness patterns also varied somewhat with proband
      characteristics. CONCLUSIONS: Child probands with affective disorder identify
      families enriched with affective disorder (even compared with families of
      psychiatric controls), suggesting that juvenile- and adult-onset forms of this
      condition share the same diathesis. Rates of affective illness in the families of
      depressed youngsters also are notably higher than population-based estimates. The
      findings therefore indicate that very-early-onset affective disorder is familial
      and that pedigrees ascertained through affectively ill children are good
      candidates for family and genetic studies.

PMID- 9236546
TI  - Developmental precursors of affective illness in a general population birth
      cohort.
AB  - BACKGROUND: Recent evidence suggests that neurodevelopmental impairment may be a
      risk factor for later affective disorder. METHODS: Associations between childhood
      developmental characteristics and affective disorder were examined in a
      prospectively studied national British birth cohort of 5362 individuals born
      between March 3 and March 9, 1946. Mental state examinations by trained
      interviewers performed at ages 36 and 43 years identified 270 case subjects with
      adult affective disorder (AD). Teachers' questionnaires completed at age 13 and
      15 years identified 195 case subjects who had shown evidence of childhood
      affective disturbance (CAD). RESULTS: Female gender and low educational test
      scores at ages 8, 11, and 15 years were a risk factor for AD, CAD, and AD without
      CAD. In addition, attainment of motor milestones was later in the CAD group (odds
      ratio [OR] = 1.2; 95% confidence interval [CI], 1.1-1.3), followed by, and
      independent of, greater risk for speech defects between the ages of 6 and 15
      years (OR = 2.0; 95% CI, 1.3-3.0), decreased psychomotor alertness on medical
      examination between ages 4 and 11 years (OR = 4.6; 95% CI, 2.2-9.7), and an
      excess of twitching and grimacing motor behaviors in adolescence (OR = 3.9; 95%
      CI, 2.5-6.1). Persistent CAD was strongly associated with persistent AD (OR =
      7.8; 95% CI, 2.6-23.2). CONCLUSION: The findings give credence to the suggestion
      that affective disorder, especially its early-onset form, is preceded by impaired
      neurodevelopment.

PMID- 9236547
TI  - First-episode major depression. Few sex differences in course.
AB  - BACKGROUND: There is a sex difference in the prevalence of unipolar major
      depression. This study sought to determine whether there is a sex difference in
      its course. METHODS: The National Institute of Mental Health Collaborative
      Program on the Psychobiology of Depression-Clinical Studies provided data on 96
      male and 101 female subjects who were diagnosed as having a first episode of
      unipolar major depressive disorder at intake and on whom prospective data were
      available. We looked for differences at intake in factors other than sex that
      might affect the course of illness: demographic factors, characteristic features
      of the first depressive episode, psychiatric history, and family history of
      depression. We then examined the course of depression of these subjects during
      the following 15 years. RESULTS: The subjects were similar at intake, enabling us
      to focus on sex when we looked for differences in the course. Most subjects
      recovered from their first episode of major depression, but the majority had at
      least 1 recurrence in the following 5 years. During the following 15 years, male
      and female subjects did not differ significantly in the time to recovery, the
      overall time to first recurrence, of the number or severity of recurrences of
      major depressive episodes. There was no evidence for a more chronic course of
      depression in women. CONCLUSION: There were few significant sex differences in
      the course of major depressive disorder in this study population.

PMID- 9236548
TI  - Clinical improvement with fluoxetine therapy and noradrenergic function in
      patients with panic disorder.
AB  - BACKGROUND: Central noradrenergic (NA) dysregulation has provided a major
      theoretical framework for understanding the pathogenesis of panic disorder (PD).
      Using clonidine, an alpha 2-adrenergic receptor agonist, as a probe of NA
      function, we investigated the hypothesis that the antipanic efficacy of the
      selective serotonin reuptake inhibitors may be associated with normalization of a
      putatively dysregulated NA system. METHODS: We report further analyses on data
      from 17 subjects with PD and 16 healthy volunteers who underwent measurement of
      the plasma NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) immediately
      before and after oral clonidine administration. Thirteen patients with PD were
      rechallenged after 12 weeks during open fluoxetine hydrochloride treatment using
      the same clonidine paradigm; 13 healthy volunteers were rechallenged at 12 weeks,
      not having received treatment between challenges. RESULTS: Patients with PD,
      compared with healthy volunteers, have markedly elevated plasma MHPG volatility
      during the first clonidine challenge. Volatility describes the magnitude of
      within-subject plasma MHPG oscillatory activity as assessed by the root of the
      mean square successive difference. A greater degree of clinical global
      improvement was predicted by a greater magnitude of basal MHPG reduction with
      fluoxetine treatment. Antipanic response to fluoxetine was accompanied by a
      significant decrease of MHPG volatility to volunteer levels. Volunteer MHPG
      volatility remained unchanged from the first to second clonidine challenge.
      CONCLUSIONS: Further evidence is provided for the hypothesis of NA dysregulation
      in PD as reflected by elevations of within-subjects plasma MHPG volatility during
      clonidine challenge. Effective selective serotonin reuptake inhibitor-antipanic
      treatment in this clinical sample was paralleled by normalization of dysregulated
      NA function.

PMID- 9236549
TI  - Disrupted pattern of D2 dopamine receptors in the temporal lobe in schizophrenia.
      A postmortem study.
AB  - BACKGROUND: Anatomical substrates for the clinical efficacy of D2 dopamine
      receptor antagonism in ameliorating positive symptoms, including auditory
      hallucinations, in schizophrenia are not fully known. We previously identified a
      modular organization of D2 receptors unique to the temporal lobe. The dense bands
      of D2 receptors showed highest frequency in auditory and speech association
      cortices (Brodmann areas 22, 39, and 42) and auditory-visual association areas
      (Brodmann areas 20 and 37) but were rarely found in somatosensory association
      regions (Brodmann area 21). Since the anatomical localization of these bands
      mirrors the presumed sites underlying hallucinations in schizophrenia, the
      modular and laminar distribution of D2 receptors was studied in the temporal
      cortex in the brains of schizophrenic and control subjects. METHODS: Tissue
      obtained post mortem from 12 elderly schizophrenic subjects and 13 controls
      matched for age and postmortem interval was examined by quantitative receptor
      autoradiography for D2 receptor binding with [125I]epidepride. All regions of the
      temporal lobe were sampled in all cases. RESULTS: Schizophrenia cases exhibited
      significantly disrupted patterns of D2 receptors in the perirhinal, superior, and
      inferior temporal cortices, including disrupted patterns in the modular D2
      receptor bands. The schizophrenic cases had reduced concentrations of D2
      receptors in the supragranular layers and elevated concentrations of D2 receptors
      in the granular layer in isocortical regions of the temporal lobe. This
      disruption does not appear to be due to long-term treatment of antipsychotic
      drugs and is regionally specific as there were no differences between groups for
      concentrations or patterns of expression in the hippocampal complex. CONCLUSIONS:
      Blockade of the disrupted distribution of D2 receptors in auditory and auditory
      visual association cortices is a likely mechanism for the clinical efficacy of D2
      antagonists in reducing hallucinations. The regionally specific, aberrant pattern
      of D2 receptors may be a symptom of anomalous cortical development in these
      regions.

PMID- 9236550
TI  - Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects
      with schizophrenia. Regional and diagnostic specificity.
AB  - BACKGROUND: Multiple lines of evidence indicate that the prefrontal cortex is a
      site of dysfunction in schizophrenia. However, the apparent absence of gross
      structural abnormalities in this area suggests that the pathophysiological
      characteristics of schizophrenia may involve more subtle disturbances in
      prefrontal cortical circuitry, such as alterations in synaptic connectivity and
      transmission. In this study, immunoreactivity for synaptophysin, an integral
      membrane protein of small synaptic vesicles, was used to assess the integrity of
      cortical synaptic circuitry in schizophrenia. METHODS: Using immunocytochemical
      techniques and adjusted optical density measurements, we examined synaptophysin
      immunoreactivity in prefrontal cortical areas 9 and 46 and in area 17 (the
      primary visual cortex) from 10 pairs of case subjects with schizophrenia and
      control subjects. matched on a pairwise basis for age, sex, race, and postmortem
      interval, and in 5 matched pairs of nonschizophrenic psychiatric case subjects
      and normal control subjects. RESULTS: Compared with levels found in matched
      control subjects, synaptophysin immunoreactivity in areas 46 and 9 was
      significantly decreased (P < .001 and P < .008, respectively) across all cortical
      layers in the case subjects with schizophrenia. In contrast, no differences were
      observed in area 17. In addition, levels of synaptophysin immunoreactivity in
      areas 46, 9, and 17 did not differ between 5 nonschizophrenic psychiatric case
      subjects and their matched controls, suggesting that decreased synaptophysin
      levels in the prefrontal cortex of patients with schizophrenia may be specific to
      that disorder. CONCLUSION: Additional studies are required to determine if the
      decrease in levels of synaptophysin immunoreactivity is caused by a decrease in
      the number or size of presynaptic terminals, a decrease in the number of synaptic
      vesicle per terminal, or a decrease in the expression of synaptophysin. However,
      all of these potential explanations are consistent with a disturbance in synaptic
      transmission in the prefrontal cortex of patients with schizophrenia.

PMID- 9236551
TI  - Maternal smoking during pregnancy and the risk of conduct disorder in boys.
AB  - BACKGROUND: Previous animal and human studies have indicated that prenatal
      exposure to nicotine is associated with adverse reproductive outcomes, including
      altered neural structure and functioning, cognitive deficits, and behavior
      problems in the offspring. Our study extends previous research on humans by
      controlling a broad range of correlates of maternal smoking during pregnancy to
      determine if smoking is associated with behavior problems in the offspring severe
      enough to qualify for DSM-III-R diagnosis. METHODS: Subjects were 177 clinic
      referred boys, ages 7 to 12 years at the time of the first assessment, who
      underwent longitudinal assessment for 6 years using annual structured diagnostic
      interviews. Correlates of maternal smoking during pregnancy and previously
      identified demographic, parental, perinatal, and family risk factors for the
      disruptive behavior disorders were controlled in logistic regression analyses.
      RESULTS: Mothers who smoked more than half a pack of cigarettes daily during
      pregnancy were significantly more likely to have a child with conduct disorder
      (odds ratio, 4.4; P = .001) than mothers who did not smoke during pregnancy. This
      association was statistically significant when controlling for socioeconomic
      status, maternal age, parental antisocial personality, substance abuse during
      pregnancy, and maladaptive parenting. CONCLUSIONS: Maternal smoking during
      pregnancy appears to be a robust independent risk factor for conduct disorder in
      male offspring. Maternal smoking during pregnancy may have direct adverse effects
      on the developing fetus or be a marker for a heretofore unmeasured characteristic
      of mothers that is of etiologic significance conduct disorder.

PMID- 9236552
TI  - The Ondine curse, false suffocation alarms, trait-state suffocation fear, and
      dyspnea-suffocation fear in panic attacks.

PMID- 9236553
TI  - A reevaluation of the risk for venous thromboembolism with the use of oral
      contraceptives and hormone replacement therapy.
AB  - BACKGROUND: There are many health benefits associated with the use or oral
      contraceptives (OCs) and hormone replacement therapy (HRT), but these agents are
      also associated with potential health risks. OBJECTIVE: To reevaluate the current
      practice of withholding OCs or HRT in women with previous venous thromboembolism
      (VTE) by critically reviewing the evidence that the use of OCs or HRT is
      associated with an increased risk for VTE. METHODS: A MEDLINE literature search
      was performed to identify studies investigating associations between OCs and VTE
      or HRT and VTE. Each study was rated according to methodologic quality (level 1,
      low potential for bias; level 2, moderate potential for bias; level 3, high
      potential for bias). Results were combined across studies of similar design to
      determine pooled risk ratios for VTE. The results from studies investigating
      third-generation OCs were reported separately. RESULTS: For OC studies (n = 22),
      the pooled risk ratios (95% confidence intervals) in case-control studies,
      retrospective cohort studies, prospective cohort studies, and randomized
      controlled trials were 3.0 (2.6-3.4), 4.8 (2.5-7.7), 2.4 (1.6-3.5), and 1.1 (0.4
      2.9), respectively. In users of third-generation OCs, the pooled risk ratio (95%
      confidence interval) for VTE was 5.0 (2.5-7.5). No study was rated as level 1, 6
      were rated as level 2, and 16 as level 3. Methodologic limitations in these
      studies would tend to exaggerate the risk for VTE with OC use. For HRT studies (n
      = 9), the pooled risk ratios (95% confidence intervals) in case-control studies,
      prospective cohort studies and randomized controlled trials were 2.4 (1.7-3.5),
      1.7 (1.0-2.9), and 0.7 (0.3-1.6), respectively. No study was rated as level 1, 6
      were rated as level 2, and 3 as level 3. CONCLUSIONS: First, an association
      between OC use and VTE is likely valid, but the reported risks are probably
      exaggerated. We estimate that users of non-third-generation OCs have a less than
      3-fold increase in the risk for VTE compared with nonusers; the risk for VTE is
      possibly higher with the use of third-generation OCs. Second, an association
      between HRT use and VTE might exist; however, further investigation is required
      before definitive conclusions can be made.

PMID- 9236554
TI  - Explicit criteria for determining potentially inappropriate medication use by the
      elderly. An update.
AB  - This study updates and expands explicit criteria defining potentially
      inappropriate medication use by the elderly. Additional goals were to address
      whether adverse outcomes were likely to be clinically severe and to incorporate
      clinical information on diagnoses when available. These criteria are meant to
      serve epidemiological studies, drug utilization review systems, health care
      providers, and educational efforts. Consensus from a panel of 6 nationally
      recognized experts on the appropriate use of medication in the elderly was
      sought. The expert panel agreed on the validity of 28 criteria describing the
      potentially inappropriate use of medication by general populations of the elderly
      as well as 35 criteria defining potentially inappropriate medication use in older
      persons known to have any of 15 common medical conditions. Updated, expanded, and
      more generally applicable criteria are now available to help identify
      inappropriate use of medications in elderly populations. These criteria define
      medications that should generally be avoided in the ambulatory elderly, doses or
      frequencies of administrations that should generally not be exceeded, and
      medications that should be avoided in older persons known to have any of several
      common conditions.

PMID- 9236555
TI  - Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with
      intramuscular immune serum globulin. A randomized controlled trial.
AB  - OBJECTIVE: To estimate the risk of sexual transmission of hepatitis C and to
      assess the value of prophylaxis with periodic intramuscular immune serum globulin
      administration. METHODS: Of 1102 steady heterosexual partners of patients with
      antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind,
      randomized, controlled trial. All the partners tested negative for antibodies to
      HCV and had normal baseline serum aminotransferase concentrations. The partners
      were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared
      from unscreened donors every 2 months (n = 450) or a placebo (n = 449). Tests for
      HCV infection were performed every 4 months. RESULTS: Eight hundred eighty-four
      partners completed the study. Seven partners became infected with HCV: 6 in the
      control group (incidence density, 12.00 per 1000 person-years; 95% confidence
      interval, 3.0 21.61) and 1 in the immune serum globulin group (incidence density,
      1.98 per 1000 person-years; 95% confidence interval, 0-5.86). The risk of
      infection was significantly higher for partners in the control group (P = .03):
      for each year approximately 1% of the partners became infected. Sequence homology
      studies strongly suggest the sexual transmission of HCV. All immune serum
      globulin lots used had high enzyme-linked immunosorbent assay titers of
      neutralizing antibodies to HCV envelope glycoproteins and high neutralization
      titers in the neutralization of binding assay. CONCLUSIONS: Hepatitis C can be
      sexually transmitted. Immune serum globulin prepared from unscreened donors
      significantly reduced the risk. The treatment was safe and well tolerated.
      Because only immune serum globulin from unscreened donors (and not from those
      screened for HCV) contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV
      immune serum globulin should be prepared from blood testing positive for
      antibodies to HCV, which is currently discarded.

PMID- 9236556
TI  - Treatment and health outcomes of women and men in a cohort with coronary artery
      disease.
AB  - BACKGROUND: Women with coronary artery disease are treated differently than men.
      Although mortality has been studied, functional outcomes for women and men have
      not been prospectively compared. METHODS: The Manitoba Health Reform Impact Study
      used hospital databases to identify all residents aged 45 years and older in
      Manitoba who were hospitalized for a myocardial infarction between October 1,
      1991, and September 30, 1992. Cohort members were interviewed twice, an average
      of 16 and 25 months after hospitalization. Baseline and follow-up measures
      included treatments (eg, physician visits, diagnostic testing, revascularization,
      and cardiac medications), physical health status (physical component summary
      [PCS] score derived from the Medical Outcomes Study Short Form 36), reinfarction,
      and mortality. RESULTS: Of the 820 patients who completed the initial survey, 31
      died during the follow-up period, and 734 completed the follow-up survey. Data
      were complete for the primary outcome (PCS score) and all relevant covariates for
      the 677 patients who were included in this study Women constituted 34% of this
      cohort. Although women had more physician visits during follow-up, they were less
      likely to have undergone treadmill testing or angiography (odds ratio, 0.68; 95%
      confidence interval, 0.46-0.99). Women were equally likely to report taking beta
      adrenergic blocking agents, but were less likely than men to report the use of
      aspirin (odds ratio, 0.69; 95% confidence interval, 0.48-0.98). After adjusting
      for baseline differences in PCS scores, age, income, social supports, and the
      levels of angina and dyspnea, the PCS score for women declined by 1.4 points,
      while the score for men improved by 0.2 points (P = .03). During the follow-up
      period, reinfarction and mortality rates were low overall, but were not different
      in men and women. CONCLUSIONS: In this cohort of patients with known coronary
      artery disease, we found less aggressive treatment of coronary artery disease and
      less use of aspirin among women than among men during 1 year of observation.
      After controlling for baseline differences, women with coronary artery disease
      experienced a more rapid decline in physical health status than did men during 1
      year of follow-up.

PMID- 9236558
TI  - Medication-prescribing errors in a teaching hospital. A 9-year experience.
AB  - BACKGROUND: Improved understanding of medication prescribing errors should be
      useful in the design of error prevention strategies. OBJECTIVE: To report
      analysis of a 9-year experience with a systematic program of detecting,
      recording, and evaluating medication-prescribing errors in a teaching hospital.
      METHODS: All medication-prescribing errors with potential for adverse patient
      outcome detected and averted by staff pharmacists from January 1, 1987, through
      December 31, 1995, were systematically recorded and analyzed. Errors were
      evaluated by type of error, medication class involved, prescribing service,
      potential severity, time of day, and month. Data were analyzed to determine
      changes in medication-prescribing error frequency and characteristics occurring
      during the 9-year study period. RESULTS: A total of 11,186 confirmed medication
      prescribing errors with potential for adverse patient consequences were detected
      and averted during the study period. The annual number of errors detected
      increased from 522 in the index year 1987 to 2115 in 1995. The rate of errors
      occurring per order written, per admission, and per patient-day, all increased
      significantly during the study duration (P < .001). Increased error rates were
      correlated with the number of admissions (P < .001). Antimicrobials,
      cardiovascular agents, gastrointestinal agents, and narcotics were the most
      common medication classes involved in errors. The most common type of errors were
      dosing errors, prescribing medications to which the patient was allergic, and
      prescribing inappropriate dosage forms. CONCLUSIONS: The results of this study
      suggest there may exist a progressively increasing risk of adverse drug events
      for hospitalized patients. The increased rate of errors is possibly associated
      with increases in the intensity of medical care and use of drug therapy. Limited
      changes in the characteristics of prescribing errors occurred, as similar type
      errors were found to be repeated with increasing frequency. New errors were
      encountered as new drug therapies were introduced. Health care practitioners and
      health care systems must incorporate adequate error reduction, prevention, and
      detection mechanisms into the routine provision of care.

PMID- 9236557
TI  - Occupational injury and illness in the United States. Estimates of costs,
      morbidity, and mortality.
AB  - OBJECTIVE: To estimate the annual incidence, the mortality and the direct and
      indirect costs associated with occupational injuries and illnesses in the United
      States in 1992. DESIGN: Aggregation and analysis of national and large regional
      data sets collected by the Bureau of Labor Statistics, the National Council on
      Compensation Insurance, the National Center for Health Statistics, the Health
      Care Financing Administration, and other governmental bureaus and private firms.
      METHODS: To assess incidence of and mortality from occupational injuries and
      illnesses, we reviewed data from national surveys and applied an attributable
      risk proportion method. To assess costs, we used the human capital method that
      decomposes costs into direct categories such as medical and insurance
      administration expenses as well as indirect categories such as lost earnings,
      lost home production, and lost fringe benefits. Some cost estimates were drawn
      from the literature while others were generated within this study. Total costs
      were calculated by multiplying average costs by the number of injuries and
      illnesses in each diagnostic category. RESULTS: Approximately 6500 job-related
      deaths from injury, 13.2 million nonfatal injuries, 60,300 deaths from disease,
      and 862,200 illnesses are estimated to occur annually in the civilian American
      workforce. The total direct ($65 billion) plus indirect ($106 billion) costs were
      estimated to be $171 billion. Injuries cost $145 billion and illnesses $26
      billion. These estimates are likely to be low, because they ignore costs
      associated with pain and suffering as well as those of within-home care provided
      by family members, and because the numbers of occupational injuries and illnesses
      are likely to be undercounted. CONCLUSIONS: The costs of occupational injuries
      and illnesses are high, in sharp contrast to the limited public attention and
      societal resources devoted to their prevention and amelioration. Occupational
      injuries and illnesses are an insufficiently appreciated contributor to the total
      burden of health care costs in the United States.

PMID- 9236559
TI  - Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with
      acquired immunodeficiency syndrome.
AB  - BACKGROUND: Fever is commonly observed in patients with human immunodeficiency
      virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow
      biopsy in the diagnosis of fever of unknown origin in patients infected with HIV
      remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive
      patients with 137 episodes of fever lasting 10 or more days without diagnosis
      after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS:
      Overall, a specific diagnosis was achieved in 52 episodes by means of culture and
      histopathological examination (diagnostic yield, 37.9%). Three types of disease
      were found: mycobacterial infections (n = 36, 69% of documented episodes),
      including 18 patients with disseminated tuberculosis and 14 with Mycobacterium
      avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and
      visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more
      sensitive than microscopic examination with special stains for the diagnosis of
      mycobacterial infections, the pathological examination of bone marrow led to a
      more rapid diagnosis of disease. In addition, the histopathological examination
      of bone marrow alone led to the diagnosis of a specific condition in 43 episodes
      (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure
      for the diagnosis of fever in patients with advanced HIV disease, particularly in
      areas where tuberculosis and leishmaniasis are prevalent. Involvement of the
      marrow may be the first indication of the existence of extranodal non-Hodgkin
      lymphoma. For Mycobacterium avium-intracellulare complex infection, blood
      cultures were more sensitive than bone marrow biopsy.

PMID- 9236560
TI  - Comparison of behavior therapy with and without very-low-energy diet in the
      treatment of morbid obesity. A 5-year outcome.
AB  - BACKGROUND: Very-low-energy diets (VLEDs) together with behavior therapy (BT) are
      widely used in the treatment of morbid obesity, but there is no evidence of their
      long-term effectiveness as compared with behavior therapy alone. METHODS: Fifty
      nine morbidly obese patients (25 men and 34 women; mean weight, 132.8 +/- 20.7
      kg; mean age, 43.1 +/- 9.2 years) were treated with combined therapy of VLED and
      BT or BT alone. No maintenance program was used. Eighty-seven percent of eligible
      patients were contacted 4.8 to 6.2 years after the program. RESULTS: During
      treatment, 56% of patients dropped out of the VLED + BT group and 28% from the BT
      group (P = .03). High scores on the Symptom Checklist-90R before treatment
      predicted dropout from the VLED+BT group, but not from BT. At the end of therapy,
      mean weight change was -22.9 kg in the VLED+BT group and -8.9 kg in the BT group
      (P < .001). The overall weight change from pretreatment to the 5-year follow-up
      was greater in the VLED+BT group than in the BT group (-16.9 kg vs -4.9 kg,
      respectively; P = .03). Men succeeded better in the VLED+BT group than in BT.
      Among the dropouts, the mean weight change from baseline was +5.2 kg in the
      VLED+BT group and +13.0 kg in the BT group. CONCLUSIONS: Our data suggest that in
      the treatment of morbid obesity, VLED combined with BT may produce a better 5
      year maintenance than BT alone, especially among men. A satisfactory weight loss
      can be achieved without a maintenance program.

PMID- 9236561
TI  - Efficacy of nefopam for the prevention and treatment of amphotericin B-induced
      shivering.
AB  - BACKGROUND: Shivering is experienced by up to 70% of patients undergoing
      amphotericin B therapy. Treatment with meperidine hydrochloride, currently the
      most widely used medication for controlling amphotericin B-induced shivering, was
      compared with nefopam hydrochloride, which has been successfully used to treat
      post-operative shivering. METHODS: Forty-five patients with cancer and systemic
      fungal infections randomly received nefopam hydrochloride, 0.3 mg/kg, meperidine
      hydrochloride, 0.7 mg/kg, or saline solution intravenously 15 minutes before the
      cessation of amphotericin B infusion (1 mg/kg for 45 minutes). If shivering
      persisted, patients in the control (saline solution) group received either
      nefopam hydrochloride, 0.3 mg/kg, or meperidine hydrochloride, 0.7 mg/kg.
      RESULTS: Occurrence of shivering 15 minutes after the cessation of amphotericin B
      infusion was significantly less frequent in the nefopam (6.6%) and meperidine
      (40%) groups compared with the control group (66.6%). The incidence of shivering
      in the nefopam group with respect to the meperidine group was also significantly
      reduced. Moreover, nefopam administration to 5 persistently shivering patients in
      the control group definitively stopped the shivering in all of them (100%) in a
      mean (+/- SD) time of 29.1 +/- 4.8 seconds, while meperidine terminated shivering
      in 4 (80%) of 5 patients in a mean (+/- SD) time of 200.0 +/- 30.2 seconds. The
      adverse reactions that can be ascribed to nefopam or meperidine use were nausea
      and sedation, respectively, and may be considered negligible. CONCLUSION: Nefopam
      seems to be more effective than meperidine in preventing and quickly suppressing
      amphotericin B-induced shivering.

PMID- 9236562
TI  - A double-blind, placebo-controlled study of the effectiveness and safety of
      nizatidine in the prevention of postprandial heartburn.
AB  - BACKGROUND: Heartburn is frequently associated with overindulgence in food and
      drink, meal-stimulated gastric acid secretion, and a gastroesophageal reflux with
      a pH of 4 or lower. Nizatidine is a selective histamine2 receptor antagonist that
      effectively suppresses gastric acid secretion at lower than prescription doses
      and has been approved for nonprescription use in the prevention of postprandial
      heartburn. OBJECTIVE: To examine the relative effectiveness of 3 dose levels of
      nizatidine (225 mg, 75 mg, and 25 mg) in preventing postprandial heartburn.
      METHODS: Four hundred thirteen subjects with documented moderate to severe
      heartburn following a standard meal that provoked heartburn were randomized to
      receive a single dose of nizatidine at 225 mg (n = 104), 75 mg (n = 101), or 25
      mg (n = 105), or placebo (n = 103) 30 minutes before the meal, at 30 minutes
      (immediately after completing the meal), and at 60, 90, 120, 150, 180, and 210
      minutes (from beginning the meal), subjects assessed the presence or absence of
      heartburn (yes or no) and the severity of heartburn (100-mm visual analog scale).
      RESULTS: The use of both 225 mg and 75 mg of nizatidine were significantly better
      than placebo in preventing heartburn in the proportion of subjects with complete
      prevention of heartburn (15 [14.4%] and 15 [14.9%], respectively, vs 3 [2.9%]; P
      < .001); the effects of nizatidine, 25 mg, in 7 subjects (7%) were not
      distinguishable from placebo. Similar results for nizatidine, 225 mg and 75 mg,
      were seen for longest duration of no heartburn, total duration of no heartburn,
      the average severity of heartburn, and the peak heartburn severity. All 3 doses
      of nizatidine were superior to placebo (P < .001) in reducing average and peak
      heartburn severity and were well tolerated. CONCLUSIONS: Single doses of 225 mg
      and 75 mg of nizatidine administered 30 minutes before a standard meal intended
      to provoke heartburn are significantly more effective than placebo for the
      prevention and/or reduction of postprandial heartburn.

PMID- 9236563
TI  - Internal medicine, psychiatry, and emergency medicine residents' views of
      assisted death practices.
AB  - BACKGROUND: Although studies have revealed conflicting attitudes within the
      medical community regarding assisted death practices in the United States, the
      views of current resident physicians have not been described. OBJECTIVE: To
      investigate the perspectives of residents from 3 medical specialty fields
      regarding the acceptability of assisted suicide and euthanasia practices as
      performed by 4 possible agents (the resident personally, a referral physician,
      physicians in general, or nonphysicians in general) in 6 patient scenarios.
      METHODS: An anonymous survey exploring responses to 6 patient vignettes was
      conducted with a convenience sample of all residents in the internal medicine,
      psychiatry, and emergency medicine training programs. RESULTS: A total of 96
      residents, 72% of those asked, participated in this study. Overall, residents
      expressed opposition or uncertainty regarding assisted suicide and euthanasia.
      The residents were disinclined to directly perform such practices themselves and
      did not support the conduct of assisted suicide practices by nonphysicians.
      Respondents were somewhat more accepting of other physicians' involvement in
      assisted death activities. Conflicting views were expressed by residents, with
      emergency medicine residents more likely to support assisted suicide practices in
      4 of 6 patient vignettes than either internal medicine or psychiatry residents.
      Residents who reported being influenced by religious beliefs (21 respondents
      [22%]) did not support assisted death practices, whereas those influenced by
      personal philosophy (74 respondents [77%]) expressed less opposition.
      CONCLUSIONS: This study explores the uncertainty and differing views of residents
      from 3 fields about physician-assisted suicide practices. Study findings are
      considered within the larger literature on clinician attitudes toward assisted
      suicide and euthanasia.

PMID- 9236564
TI  - Diabetic muscular infarction. Preventing morbidity by avoiding excisional biopsy.
AB  - Focal infarction of skeletal muscle is a complication of diabetes mellitus. In
      the appropriate clinical setting and with characteristic magnetic resonance
      imaging (MRI) findings, prompt diagnosis can prevent unnecessary morbidity by
      avoiding excisional biopsy. We report a case of diabetic muscular infarction
      presenting as a painful thigh mass and review diagnostic and management
      principles.

PMID- 9236565
TI  - Effect of tamoxifen on von Willebrand factor levels.

PMID- 9236567
TI  - Visual loss as a causative factor in visual hallucinations associated with
      Parkinson disease.

PMID- 9236568
TI  - Asymptomatic carotid artery stenosis.

PMID- 9236566
TI  - Warfarin use in Medicare patients with atrial fibrillation.

PMID- 9236569
TI  - Patent foramen ovale in patients with cerebral infarction. A transesophageal
      echocardiographic study.
AB  - OBJECTIVES: To determine the frequency of patent foramen ovale (PFO) among
      various subtypes of cerebral infarction. To determine whether any historical or
      clinical characteristics predict the presence or absence of PFO in these
      patients. DESIGN: Comorbidity and infarct subtype study. SETTING: Referral-based
      study. PATIENTS: One hundred sixteen patients with cerebral infarction
      consecutively referred for transesophageal echocardiography during a 6-month
      period. MAIN OUTCOME MEASURES: Infarct subtype classification was made using a
      clinical and radiographic diagnostic rubric similar to that used by the Stroke
      Data Bank of the National Institute of Neurological Diseases and Stroke. The
      frequency of various risk factors and clinical characteristics in patients with
      and in those without PFO and the frequency of PFO in patients with various
      infarct subtypes were compared (chi 2 or Fisher exact tests). RESULTS: Patent
      foramen ovale was detected in 37 patients (32%). Mean age was similar in those
      with (60 years) and those without (64 years) PFO. Patent foramen ovale was more
      frequent among men (39%) than women (20%, P = .03). Patients with PFO had a lower
      frequency of atrial fibrillation, diabetes mellitus, hypertension, and peripheral
      vascular disease compared with those without PFO. There was no difference in
      frequency of the following characteristics in patients with PFO compared with
      those without PFO: pulmonary embolus, chronic obstructive pulmonary disease,
      pulmonary hypertension, peripheral embolism, prior cerebral infarction,
      nosocomial cerebral infarction, Valsalva maneuver at the same time of cerebral
      infarction, recent surgery, or hemorrhagic transformation of cerebral infarction.
      Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of
      uncertain cause and in 15 (25%) of 61 with infarcts of known cause
      (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P = .08).
      When the analysis was restricted to patients who underwent Valsalva maneuver, PFO
      with right to left or bidirectional shunt was found in 19 (50%) of 38 patients
      with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known
      cause (P = .01). CONCLUSION: Although PFO was overrepresented in patients with
      infarcts of uncertain in our and other studies, it has a high frequency among
      patients with cerebral infarction of all types. The relation between PFO and
      stroke requires further study.

PMID- 9236570
TI  - Comparison of carotid endarterectomy outcomes from randomized controlled trials
      and Medicare administrative databases.
AB  - OBJECTIVE: To compare the characteristics and outcomes demonstrated for
      participants in randomized controlled trials of carotid endarterectomy with those
      of the Medicare patient population who received the procedure in 1989. DESIGN:
      Historical cohort study using Medicare claims data. SETTING: Medicare beneficiary
      population aged 65 years and older. PATIENTS: Medicare patients 65 years and
      older who received carotid endarterectomy during 1989. MAIN OUTCOME MEASURES:
      Perioperative mortality rate and occurrence of transient ischemic attack, stroke,
      and death within 2 years of surgery. RESULTS: The risk for death within 2 years
      of the procedure was substantially higher among Medicare patients who received
      surgery in hospitals with perioperative mortality rates greater than rates
      demonstrated in the trials (odds ratio, 1.36; 95% confidence interval, 1.29-1.44)
      and among those with comorbidity that exceeded trial participation criteria (odds
      ratio, 1.72; 95% confidence interval, 1.64-1.84). CONCLUSIONS: Although carotid
      endarterectomy trials demonstrate the efficacy of the procedure, this evidence
      only applies to patients and hospitals with characteristics comparable to those
      of the trial participants. The importance of this consideration is demonstrated
      by the substantially higher odds of death experienced among Medicare patients
      receiving the procedure who had a level of comorbidity that exceeded that of the
      trial participants or who received their surgery in a hospital with a
      perioperative mortality rate that exceeded the experience of the hospitals in the
      trials.

PMID- 9236571
TI  - Effect of tacrine on language, praxis, and noncognitive behavioral problems in
      Alzheimer disease.
AB  - OBJECTIVE: To examine the effects of tacrine hydrochloride in patients with
      Alzheimer disease (AD) and detectable baseline deficits in discrete cognitive and
      noncognitive parameters who are enrolled in a previously reported multicenter,
      double-blind, 30-week trial. DESIGN: An exploratory analysis using last
      observation carried forward. The study population included a placebo group (n =
      181) and all patients randomized to treatment within 160 mg/d of tacrine
      hydrochloride (n = 234), regardless of highest dose achieved or duration of
      tacrine therapy. STUDY POPULATION: Male and female subjects, at least 50 years of
      age, with mild to moderate AD and detectable baseline deficits in discrete
      cognitive and noncognitive parameters. MAIN OUTCOME MEASURES: Change from
      baseline to last observation carried forward in discrete subscale scores of the
      Alzheimer's Disease Assessment Scale (ADAS): cognitive (memory, language, praxis)
      and noncognitive (mood, behavior). Improvement was defined as a decrease of at
      least 1 point from baseline; stabilization was defined as no change or a decrease
      from baseline. RESULTS: Compared with the placebo group, the percentage of
      patients receiving tacrine whose conditions improved or stabilized was
      significantly greater for 8 of 11 ADAS-cognitive items (word recall, word
      recognition, orientation, language production, comprehension, word finding,
      following commands, ideational praxis) and for the ADAS-noncognitive items:
      cooperation, delusions, and pacing. CONCLUSIONS: Tacrine stabilizes or improves
      specific behavioral deficits and symptoms in AD. The previous demonstration of
      tacrine's effect on global cognitive function has been extended by suggesting an
      association between tacrine therapy and improvements in individual cognitive and
      noncognitive items of the ADAS. Effects of tacrine in clinical practice might be
      more accurately and efficiently assessed by measuring individual ADAS cognitive
      and noncognitive items relevant to individual patient pretreatment clinical
      status.

PMID- 9236572
TI  - Pupil dilation to tropicamide is not specific for Alzheimer disease.
AB  - BACKGROUND: The extent of pupil dilation after instillation of a dilute
      tropicamide solution was proposed as a noninvasive neurobiological diagnostic
      test for Alzheimer disease (AD). Pupils in patients with AD dilated 23% vs only
      5% in control subjects. OBJECTIVE: To determine whether pupil dilation in
      response to tropicamide distinguishes patients with AD from control subjects
      without dementia. METHODS: There were 50 patients with AD and 51 control
      subjects; no participant had primarily ocular pathological conditions or took
      drugs that affected cholinergic tone. All participants received 1 drop of 0.01%
      tropicamide in 1 eye and 1 drop of 0.9% saline solution in the other eye in
      random order. Pupil measurements were obtained using a pupil and corneal
      reflection tracking system (RK-426 PC system, ISCAN Inc, Burlington, Mass) that
      illuminated the eye with a low-level infrared source and measured pupil
      diameters, fixation, and light level every 16.7 milliseconds during each 30
      second-measurement. Pupil measurements were obtained from each eye at baseline
      and 5, 10, 15, and 30 minutes after drop instillation. RESULTS: The increase in
      pupil size after tropicamide instillation was equal between patients with AD and
      control subjects. The mean (+/- SD) pupil diameter increased from 4.5 +/- 1.1 to
      5.5 +/- 1.1 mm after 30 minutes in patients with AD and from 4.7 +/- 0.9 to 5.8
      +/- 0.9 mm in control subjects. Anisocoria and the mean rate of dilation did not
      differ between patients with AD and control subjects. Eye color and corneal
      moisture did not affect these results. The extent of pupil dilation in patients
      with AD was not related to clinical estimates of dementia severity. CONCLUSION:
      Pupil dilation in response to instillation of 0.01% tropicamide is not useful as
      an antemortem diagnostic test for AD.

PMID- 9236573
TI  - The impact of neurologic disease on hospitalizations related to human
      immunodeficiency virus infection in Maryland, 1991-1992.
AB  - OBJECTIVES: To determine the impact of neurologic disease on length of stay and
      total hospital charges for hospitalizations related to human immunodeficiency
      virus (HIV) infection. DESIGN: Review of all HIV-related hospitalizations from
      all acute nonfederal hospitals in Maryland in 1991 and 1992. Neurologic status
      and HIV disease status were determined by codes from the International
      Classification of Diseases, Ninth Revision Clinical Modification, in an
      administrative database. Total hospital charges and length of stay were also
      included in this database. RESULTS: Of 12 128 HIV-related hospitalizations (6013
      patients with the acquired immunodeficiency syndrome [AIDS], 308 HIV-seropositive
      patients with symptoms without AIDS, and 5807 HIV-seropositive patients without
      symptoms), neurologic disease occurred in 1013 (8.4%), predominantly in patients
      with AIDS. In all HIV-seropositive patients, those with primary neurologic
      disease had a long mean (+/- SD) length of stay (16.4 +/- 16.5 days vs 9.3 +/-
      11.3 days; P < .001) and higher mean (+/- SD) total charges ($12,733 +/- $12,009
      vs $8069 +/- $11,247; P < .001) than those without neurologic disease. In
      patients with AIDS, those with primary neurologic disease also had a longer mean
      (+/- SD) length of stay (17.2 +/- 17.2 days vs 11.7 +/- 12.7 days; P < .001) and
      higher mean (+/- SD) total charges ($13,430 +/- $12,470 vs $10,794 +/- $13,537; P
      < .001) than those without neurologic disease. After adjustment for age, sex,
      race, and stage of HIV infection in all HIV-seropositive patients, our results
      indicated that neurologic disease increased the length of stay by 3.3 days (95%
      confidence interval [CI], 2.9-3.8) and total charges by $2552 (95% CI, $2111
      $2993). After adjustment for age, sex, and race in discharged patients with AIDS,
      the results showed that neurologic disease increased length of stay by 2.24 days
      (95% CI, 0.73-3.77) and total charges by $1512 (95% CI, $40-$2894). CONCLUSION:
      Neurologic disease increases the length of stay and total hospital charges of HIV
      infected patients.

PMID- 9236574
TI  - Central nervous system relapse in non-Hodgkin lymphoma. A single-center study of
      532 patients.
AB  - OBJECTIVES: To define the cumulative risk of central nervous system (CNS) relapse
      in systemic non-Hodgkin lymphoma (NHL); to assess the risk factors of age, sex,
      malignancy grade, stage, localization, and response to initial therapy; and to
      evaluate the effect of CNS prophylaxis. PATIENTS AND METHODS: An unselected group
      of 532 patients with systemic NHL. A retrospective analysis. RESULTS: Eleven
      patients presented with systemic as well as CNS localization, whereas in 55
      patients, CNS relapse occurred later. The cumulative risk of CNS relapse at 4
      years for all 532 patients was 19%. High-grade NHL carried a 39% risk of CNS
      relapse, with the vast majority of relapses occurring in the first 14 months
      after the initial diagnosis. The cumulative risk in patients with intermediate
      grade NHL was considerable (22%) and dispersed throughout a much longer period (6
      years). Patients with low-grade NHL still carried a 7% risk of CNS relapse; in
      all these patients, low malignancy grade was transformed into a higher malignancy
      grade at that time. In a multivariate analysis, high- and intermediate-grade NHL
      and advanced stage were independent risk factors for CNS relapse. There was not
      any strong evidence for a beneficial role of CNS prophylaxis in patients with
      intermediate- and high-grade NHL, but a retrospective analysis cannot be
      conclusive with regard to the effect of therapy. Systemic relapse occurred
      rapidly after CNS relapse, resulting in a median survival time after CNS relapse
      of only 2 months. CONCLUSIONS: Patients with high- and intermediate-grade NHL
      carry a considerable risk of CNS relapse. Advanced stage is an additional
      independent risk factor. The role of CNS prophylaxis seems to be disappointing,
      but a retrospective analysis cannot be conclusive. Prognosis after CNS relapse is
      poor.

PMID- 9236575
TI  - Role of antiribosomal P protein antibodies in the diagnosis of lupus isolated to
      the central nervous system.
AB  - BACKGROUND: When lupus presents with isolated central nervous system findings,
      the usual serologic markers are often absent and diagnostic difficulty with a
      delay in treatment is common. OBJECTIVE: To report the usefulness of
      antiribosomal P protein antibodies in the diagnosis of lupus isolated to the
      central nervous system when results of tests for anti-double-stranded DNA
      antibodies are negative. DESIGN: Case report. SETTING: University medical center.
      PATIENT: The patient was evaluated and treated on referral and follow up for 1
      year. RESULTS: We describe a patient with acute onset of psychosis followed by
      coma and focal clonic movements with undetectable DNA antibodies. Serum
      antiribosomal P protein antibody levels were elevated. Steroid therapy was
      followed by marked clinical improvement and a decrease in antibody titer.
      CONCLUSION: Antiribosomal P protein antibodies provide an important confirmatory
      test for the diagnosis of lupus isolated to the central nervous system when
      results of tests for anti-double-stranded DNA antibodies are negative.

PMID- 9236576
TI  - Emotional arousal and phobia in transient global amnesia.
AB  - OBJECTIVE: To evaluate the role of emotionally stressful or phobogenic events and
      phobic personality traits in transient global amnesia (TGA). DESIGN: Case-control
      study. SETTING: Tertiary care center. PATIENTS: Fifty-one case patients with TGA
      (mean +/- SD age, 62.7 +/- 6.7 years) compared with 51 control patients with
      transient ischemic attacks (mean +/- SD age, 63.8 +/- 6.7 years). MAIN OUTCOME
      MEASURES: Precipitant factors, life events, and phobic attitudes. RESULTS: Of the
      25 TGA attacks that were triggered by a precipitant, 11 were possibly related to
      emotionally stressful or phobogenic situations. On a scale that measured phobic
      attitudes, the case patients with TGA scored significantly higher than the
      control patients with transient ischemic attacks (mean +/- SD total score, 15.21
      +/- 11.0 vs 4.41 +/- 5.2; P < .001 by corrected analysis of variance for age,
      sex, and education). The amount of stressful live events in the year that
      preceded the attack did not differ between the case patients with TGA and the
      control patients with transient ischemic attacks. CONCLUSION: The results support
      the hypothesis that emotional arousal and phobia are involved in TGA.

PMID- 9236577
TI  - Neurological and psychiatric predictors of mortality in patients with Alzheimer
      disease in California.
AB  - OBJECTIVE: To determine whether neurological and psychiatric symptoms predict
      survival time among patients with Alzheimer disease (AD) after adjusting for the
      influence of sociodemographic variables, health conditions, and dementia severity
      separately for men and women. DESIGN: The sample consisted of 936 men and women
      diagnosed as having probable or possible AD at 1 of 7 Alzheimer's Disease
      Diagnostic and Treatment Centers throughout California from 1986 through 1990.
      Data on dementia severity, comorbid conditions, and demographic characteristics
      were collected at the time of AD diagnosis. Data on vital status and dates of
      death were obtained by linking the patient file to several administrative
      databases maintained by the California State and federal governments. The mean
      length of follow-up was 31 months. Data were analyzed with Kaplan-Meier survival
      curves and Cox proportional hazards models. RESULTS: Men had shorter survival
      times than did women (log-rank test, 30.93, P < .001). Among men, but not women,
      survival times were negatively associated with selected neurological and
      psychiatric symptoms. Among women, but not men, a history of cardiovascular
      conditions was associated with poorer survival. CONCLUSIONS: Patterns of survival
      and predictors of survival time among patients with AD differ by sex. Future
      studies of survival and progression of AD need to examine men and women
      separately.

PMID- 9236578
TI  - Obstetric aspects in women with facioscapulohumeral muscular dystrophy, limb
      girdle muscular dystrophy, and congenital myopathies.
AB  - OBJECTIVE: To increase the knowledge about pregnancy and delivery in women with
      certain muscle diseases, which is important for obstetric management and family
      planning of affected women. DESIGN: The obstetric histories of patients with
      facioscapulohumeral (FSH) muscular dystrophy, limb-girdle (LG) muscular
      dystrophy, and congenital myopathies (CM) were retrospectively evaluated using
      questionnaires and medical reports. PATIENTS: The condition of 27 patients with
      different myopathies (FSH muscular dystrophy, n = 11; LG muscular dystrophy, n =
      9; and CM, n = 7 [subdivided into 5 patients with central core disease, 1 patient
      with cytoplasmic bodies, and 1 patient with unspecified myopathy]) were
      ascertained from January 1, 1992, to December 31, 1994, through departments of
      neurology and human genetics, and the German self-support group for muscle
      diseases. Fifty-eight gestations resulting in 52 live births were reviewed.
      RESULTS: Miscarriages were reported in 3 of 26 gestations in 11 patients with FSH
      dystrophy, whereas 3 of 15 pregnancies in patients with LG dystrophy were
      terminated. Preterm births occurred in 2 patients with FSH dystrophy and in 3
      patients with CM. Operative deliveries (vaginal operation or cesarean section)
      were performed in 6 of 23 gestations in patients with FSH dystrophy (1 emergency
      section), in 5 of 12 patients with LG dystrophy (2 emergency sections), and in 3
      of 17 deliveries in patients with CM. Patients with FSH dystrophy generally coped
      well with their muscle disease in pregnancy and after delivery; however, 4 women
      were stated to have difficulties in caring for their families. The situation
      differed in LG dystrophy, where most women (5 of 9) experienced worsening of
      weakness in pregnancy and required assistance after delivery. In the patients
      with CM, 3 women experienced a deterioration during pregnancy, and 4 patients
      reported difficulties after delivery. CONCLUSIONS: No deleterious outcome of
      pregnancy and labor was observed in this series of patients with muscular
      dystrophy or CM, although operative deliveries were more frequent. A significant
      aggravation of symptoms in gestation is more likely to occur in patients with
      early-onset and progressive myopathy than in those with stable disease courses.

PMID- 9236579
TI  - Human T-cell lymphotropic virus type 1 myositis, peripheral neuropathy, and
      cerebral white matter lesions in the absence of spastic paraparesis.
AB  - BACKGROUND: The human T-cell lymphotropic virus type 1 (HTLV-1) is associated
      with a chronic, progressive myelopathy termed tropical spastic paraparesis or
      HTLV-1-associate myelopathy. An increasing number of reports suggest that the
      spectrum of neurologic diseases associated with HTLV-1 is quite diverse. DESIGN:
      Case study. SETTING: A university teaching hospital (Ottawa General Hospital,
      Ottawa, Ontario). RESULTS: Serum creatine kinase levels were elevated (1091 U/L).
      Antibodies for HTLV-1 were detected by Western blot analysis and confirmed by
      polymerase chain reaction. Human immunodeficiency virus antibodies were not
      detected. Findings of nerve conduction studies revealed an axonal neuropathy,
      while results of needle electromyography were consistent with mixed neuropathic
      and myopathic changes. Findings of a muscle biopsy supported the presence of
      polymyositis. Magnetic resonance imaging scans of the brain showed chronic,
      extensive cerebral white matter involvement of more than 7 years' duration.
      Treatment with oral steroids resulted in an approximate 40% decrease in serum
      creatine kinase levels within 1 month and a marked improvement in strength.
      CONCLUSIONS: A broad spectrum of neurologic disorders is associated with HTLV-1,
      which may or may not include spastic paraparesis. Patients with myopathies and/or
      neuropathies of unknown origin who are from areas endemic for HTLV-1 should be
      screened for this retrovirus, even in the absence of spastic paraparesis.

PMID- 9236580
TI  - Limb-shaking carotid transient ischemic attacks successfully treated with
      modification of the antihypertensive regimen.
AB  - Involuntary episodic movements associated with transient cerebral ischemia are a
      rare but well-described presentation of carotid artery occlusive disease. We
      describe a young man with a left carotid artery occlusion who presented with
      daily episodes of involuntary movements of the right side that occurred for
      months. His symptoms virtually disappeared after his antihypertensive drug was
      reduced. This case supports the possibility of noninvasive management of this
      condition, which is traditionally treated with revascularization procedures.

PMID- 9236581
TI  - An unusual axonal polyneuropathy induced by low-dose interferon alfa-2a.
AB  - OBJECTIVES: To describe a patient who developed an unusual polyneuropathy after
      treatment with interferon alfa-2a for hepatitis C and to discuss issues related
      to diagnosis and pathogenesis. DESIGN: Case report. SETTING: Tertiary care
      center. CASE: A 46-year-old man with chronic hepatitis C had acute onset of an
      axonal polyneuropathy with prominent small-fiber involvement shortly after
      completing a standard 6-month course of therapy with low-dose interferon alfa-2a.
      MAIN OUTCOME AND RESULTS: Further interferon treatment for hepatitis C was
      discontinued. CONCLUSION: Standard, low-dose interferon alfa-2a treatment can
      produce a persistent predominantly small-fiber polyneuropathy.

PMID- 9236582
TI  - Choreoathetosis as a side effect of gabapentin therapy in severely neurologically
      impaired patients.
AB  - OBJECTIVE: To evaluate the relationship of gabapentin therapy with
      choreoathetotic movements in mentally retarded patients treated with intractable
      epilepsy. DESIGN: Case reports of 2 institutionalized patients who developed
      choreoathetosis temporally related to adjunctive therapy with gabapentin at
      dosages of 1200 to 1800 mg/d. RESULTS: Both patients experienced resolution of
      abnormal movements on discontinuation of the therapy. One patient developed
      recurrent choreiform movements after drug rechallenge. CONCLUSION: We suggest
      that, in patients with mental retardation and epilepsy, involuntary movements may
      either occur as reversible side effects of gabapentin therapy or result from a
      previously undescribed adverse drug interaction with other antiepileptic agents.

PMID- 9236583
TI  - Efficacy of adenoidectomy in relieving symptoms of chronic sinusitis in children.
AB  - OBJECTIVE: To determine the efficacy of adenoidectomy in relieving symptoms of
      chronic sinusitis in children. DESIGN: Retrospective case series. SETTING:
      Tertiary care center. PATIENTS: Symptoms of chronic sinusitis were studied in 48
      consecutive patients who underwent adenoidectomy or adenotonsillectomy between
      October 1993 and May 1995. Children with cystic fibrosis or those who underwent
      concurrent endoscopic sinus surgery were excluded. Patient ages ranged from 1 to
      12 years. Four patients were unavailable for follow-up and did not complete the
      study. MAIN OUTCOME MEASURES: Patients' charts were reviewed for the presence of
      preoperative symptoms, including rhinorrhea, nasal congestion, headache,
      postnasal drainage, cough, halitosis, and irritability. Also recorded were mouth
      breathing, fevers, and frequent antibiotic use. Telephone interviews with the
      patients' caregivers were conducted to collect information following the surgery
      regarding the presence of the same symptoms as well as an estimate of overall
      improvement. Follow-up ranged from 5 months to 2 years. RESULTS: The most
      frequently reported symptoms before surgery were rhinorrhea, nasal congestion,
      mouth breathing, and frequent antibiotic use (35, 37, 34, and 38 patients,
      respectively). These numbers decreased following surgery to 18, 20, 11, and 10
      patients, respectively. The average number of symptoms experienced by each
      patient decreased from 5.3 to 2.9. Complete or near symptom resolution was
      reported in 25 (58%) of 43 patients. Some improvement was reported in another 9
      patients (21%). Minimal or no improvement was reported in 9 patients (21%). To
      date, only 3 patients have gone on to have endoscopic sinus surgery. CONCLUSION:
      In the majority of cases, symptoms of chronic sinusitis in children are relieved
      by adenoidectomy.

PMID- 9236584
TI  - Outpatient adenotonsillectomy. Is it safe in children younger than 3 years?
AB  - OBJECTIVE: To evaluate the safety of ambulatory adenotonsillectomy in children
      younger than 3 years. MATERIALS AND METHODS: The records of 102 children younger
      than 3 years who underwent adenotonsillectomy as an outpatient procedure were
      reviewed during a 3-year period. RESULTS: Ten patients (10%) required overnight
      hospital admission for an average of 1.4 days. Nine patients were admitted
      directly from the day-stay unit and 1 patient was admitted 48 hours after
      surgery. The reason for hospital admission was poor oral intake. None of the
      patients had postoperative bleeding or respiratory problems or required intensive
      care unit admission. CONCLUSION: The safety of ambulatory adenotonsillectomy
      depends on judicious selection criteria and can be performed in children younger
      than 3 years.

PMID- 9236585
TI  - Power-assisted adenoidectomy.
AB  - OBJECTIVE: To quantify that the use of powered instrumentation for adenoidectomy
      is an improvement over traditional techniques. DESIGN: Retrospective case series
      of 40 consecutive children undergoing power-assisted adenoidectomy compared with
      40 consecutive children undergoing conventional transoral adenoidectomy with a
      curet. SETTINGS: Tertiary care center. MAIN OUTCOME MEASURES: Operative time,
      blood loss, length of hospitalization, and complications. RESULTS: With power
      assisted adenoidectomy, the mean operative time was significantly faster (11
      minutes vs 19 minutes for the conventional method), mean blood loss was not
      significantly different (22 mL vs 32 mL for the conventional method), mean length
      of hospitalization after the procedure was not significantly different (2.95
      hours vs 2.8 hours for the conventional method), and there were no surgical
      complications with either technique. CONCLUSION: In comparison with conventional
      techniques, power-assisted adenoidectomy provides significant advantages that are
      subjectively apparent but can also be objectively measured.

PMID- 9236586
TI  - Sickle cell disease and tonsillectomy. Preoperative management and postoperative
      complications.
AB  - BACKGROUND: Patients with sickle cell disease are recognized as having a
      relatively higher risk for postoperative complications, including fever,
      atelectasis, pneumonia, or sickle cell vas-occlusion. OBJECTIVE: To present a
      protocol for preoperative management of patients with sickle cell disease
      undergoing tonsillectomy, including the use of transfusions and intravenous
      hydration. DESIGN: Retrospective chart review. SETTING: Academic, tertiary care
      referral medical center. PATIENTS: Seventy-five patients with sickle cell disease
      who underwent tonsillectomy with or without adenoidectomy were included for
      review. Preoperative management was documented, and risk factors were assessed.
      Intraoperative management was reviewed, and postoperative complications were
      identified and compared with preoperative data and management. RESULTS:
      Preoperative management consisted of transfusions to a hemoglobin S ratio
      (hemoglobin S-total hemoglobin) less than 40% or a hemoglobin level greater than
      100 g/L. Aggressive intravenous hydration of 1.5 times the maintenance fluid was
      given 24 hours before surgery. Increased complications were associated with a
      preoperative hemoglobin S ratio greater than 40% (P < .05) and an age younger
      than 4 years (P < .05). Operative time, technique, and blood loss were not
      statistically significant risk factors. The average length of hospitalization was
      4.8 days. CONCLUSIONS: Children with sickle cell disease presenting for elective
      tonsillectomy should be given a transfusion to a hemoglobin S ratio less than 40%
      in an attempt to reduce postoperative complications. Additional factors, such as
      age and presence of obstructive sleep apnea, only increase the potential risks.

PMID- 9236587
TI  - Antibiotic treatment of children with secretory otitis media. Amoxicillin
      clavulanate is superior to penicillin V in a double-blind randomized study.
AB  - OBJECTIVE: To compare the effect of 2 different antimicrobial agents in the
      treatment of secretory otitis media (SOM). DESIGN: Prospective, double-blind,
      randomized study. PATIENTS: From a pool of 1450 children (aged 1-10 years) with
      SOM, defined by tympanometry as having type B or C2 tympanograms, 429 with SOM of
      at least 3 months' duration were included in the trial. After exclusion of 69
      patients, the remaining 360 were evenly distributed among 4 treatment groups:
      penicillin V (Primcillin) for 14 and 28 days, and amoxicillin and clavulanate
      potassium in combination (Spektramox) for 14 and 28 days. Criteria for
      improvement was a change in tympanometric findings to type C1 or type A. RESULTS:
      The success rates were in favor of amoxicillin-clavulanate treatment for 28 days
      (P < .001) (rates for respective 14- and 28-day groups: penicillin V, 23% and
      19%; amoxicillin-clavulanate, 31% and 44%). Antimicrobial therapy was more
      efficient (P < .001) in unilateral vs bilateral disease. CONCLUSION: Antibiotic
      treatment improves the middle ear status in patients with SOM, and amoxicillin
      clavulanate provides superior improvement to penicillin V.

PMID- 9236588
TI  - Pulmonary vascular complications of chronic airway obstruction in children.
AB  - OBJECTIVE: To study the clinical presentation, treatment, and outcome of
      pulmonary artery hypertension (PAH) that develops in children with chronic airway
      obstruction. DESIGN: Case study. SETTING: Academic tertiary care children's
      hospital. PATIENTS: A 3-year (October 1, 1992, to September 30, 1995) review of
      the medical records of all children with chronic airway obstruction in whom PAH
      developed. MAIN OUTCOME MEASURE: The clinical course, including objective
      laboratory data to measure PAH (cardiac catheterization, echocardiography,
      electrocardiography) both before and after treatment. RESULTS: Pulmonary artery
      hypertension developed in 18 patients. It was diagnosed using cardiac
      catheterization in 13 patients and echocardiography in 5 patients. Obstructive
      problems include chronic lung disease (9 patients), tracheobronchomalacia (6
      patients), adenotonsillar hypertrophy (5 patients), laryngomalacia (4 patients),
      macroglossia (5 patients), subglottic stenosis (2 patients), and pharyngeal
      collapse (2 patients). Nine patients were born prematurely and 7 had Down
      syndrome. Treatments included tracheotomy (7), adenotonsillectomy (5),
      adenoidectomy (3), laser epiglottoplasty (1), and supplemental oxygen (12).
      Fourteen patients had documented improvement of PAH as seen from the cardiac
      catheterization, echocardiography, or electrocardiography findings; in 4
      patients, PAH worsened (3 deaths). CONCLUSIONS: Chronic airway obstruction may
      lead to PAH. In this study, PAH was more likely to develop in premature infants
      or children with Down syndrome and cardiac anomalies. Surgery or supplemental
      oxygen will usually improve PAH, but fixed and irreversible PAH developed in
      patients with the most severe airway disease.

PMID- 9236589
TI  - Computer-assisted resection of benign sinonasal tumors with skull base and
      orbital extension.
AB  - OBJECTIVE: To use freehand, real-time, intraoperative, 3-dimensional computed
      tomography (3-D CT) localization to assist with resection of sinonasal lesions
      with skull-base and/or orbital extension. DESIGN: The 3-D CT is computer-assisted
      technology using the preoperative CT scan as a road map for resection of lesions.
      Previous technology, while resulting in little intraoperative error, required use
      of a somewhat cumbersome rigid articulated arm and attached probe, limiting
      mobility and requiring rigid fixation of the head to maintain system reference. A
      new freehand version of this technology, eliminating these limitations, has been
      used for resection of benign sinonasal lesions with skull-base and/or orbital
      extension. SETTING: Tertiary care, university-based practice. PATIENTS: Seven
      patients prospectively selected with benign lesions involving the sinonasal
      cavity and orbit and/or skull base. INTERVENTION: All patients underwent surgical
      resection of their tumors using endoscopic, open, or combined procedures with the
      assistance of freehand 3-D CT localization. MAIN OUTCOME ASSESSMENTS: Surgeon
      assessment of usefulness. RESULTS: In several cases, the device assisted the
      operator in determining the exact location of a displaced optic nerve, ensuring
      vision preservation, while in other cases, the location and depth of skull-base
      penetration was clearly determined, allowing resection via a transnasal
      endoscopic approach. In addition, the device was useful for determining the depth
      of necessary resection for optimal cosmetic result. In all cases, system accuracy
      was within less than 2 mm at the operative site. System limitations included need
      for an additional preoperative CT and time required at the beginning of the case
      for system setup and registration. CONCLUSIONS: Freehand 3-D CT, while still with
      limitations, offers the advantage of increased surgical safety, aiding anatomic
      understanding in distorted surgical fields for resection of benign sinonasal
      tumors with orbital and skull-base extension.

PMID- 9236590
TI  - Deficiency of naive T cells in patients with sudden deafness.
AB  - BACKGROUND: Although there are a number of reports concerned with the role of
      immunity in the sudden onset of progressive sensorineural hearing loss, there are
      few references dealing with the involvement of immune-mediated mechanisms in
      sudden deafness. OBJECTIVES: To study the phenotype of peripheral blood
      lymphocytes in a group of patients with sudden deafness by use of 3-color flow
      cytometry. DESIGN: The study was carried out prior to the start of steroid
      therapy. Fourteen patients underwent a follow-up study once steroid therapy had
      been completed. Prospective analysis, case-control. SETTING: Tertiary case
      referral center, ambulatory and hospitalized care. PATIENTS: Twenty-two patients
      (13 men and 9 women; mean age, 45.3 years) were compared with 14 healthy control
      subjects (9 men and 5 women; mean age, 36 years). Patients were divided in 2
      groups according to their response to steroid therapy. RESULTS: Decreased numbers
      of both CD4+ helper cells (38.4% vs 45.5%; P = .04) and CD8+ cytotoxic cells
      (17.5% vs 22.3%; P = .02) were observed in patients and compared with those in
      the control subjects, as well as reduced numbers of CD4+CD45RA+ cells (14.4% vs
      29.3%; P = .01) and CD8+CD45RA+ naive cells (18.2% vs 25.4%; P = .04). In the
      group of patients with a good response to steroid therapy (group 1), a tendency
      toward normalization of the CD4+ (pretreatment, 38.6%; posttreatment, 44.6%),
      CD4+CD45RA+ (pretreatment, 15.2%; posttreatment, 21.7%), and CD4+CD45RO+
      (pretreatment, 21.1%; posttreatment, 18.2%) cell counts was observed, with a
      slight decrease in the CD8+ population (pretreatment, 18%; posttreatment, 15.7%).
      However, in patients with a poorer response (group 2), while there were increases
      in the CD4+ (pretreatment, 38%, posttreatment, 50%) and CD4+CD45RA+
      (pretreatment, 12.8%; posttreatment, 16.7%) cell counts after steroid therapy,
      there was a significant increment in the CD4+CD45RO+ memory cell count
      (pretreatment, 14.1%; posttreatment, 28.5%) and low CD8+CD45RA+ counts
      (pretreatment, 14.6%; posttreatment, 15.5%). No differences were observed in the
      numbers of B or natural killer cells or in the presence of activation antigens
      CD25 and HLA-DR when pretreatment and posttreatment levels were compared.
      CONCLUSION: These results demonstrate significant abnormalities in the
      subpopulations of lymphocytes in patients with sudden hearing loss, suggesting
      the existence of immune-mediated responses in the inner ear as possible
      etiopathogenic factors in this entity.

PMID- 9236591
TI  - Prognostic factors in carcinoma of the external auditory canal.
AB  - BACKGROUND: Carcinomas of the external auditory canal are rare neoplasms (< 1% of
      all head and neck malignant neoplasms). OBJECTIVE: To evaluate the prognostic
      factors in 79 patients treated in a single institution. PATIENTS AND METHODS: The
      disease was staged as follows: 34 patients with stage T1 to T2 tumors; 43
      patients with stage T3 to T4 tumors; 2 patients with stage TX tumors; 68 patients
      with stage N0 tumors; and 11 patients with stage N1 tumors. The initial treatment
      was surgery in 59 patients and radiotherapy in 9 patients. Eleven patients were
      not considered candidates for treatment. RESULTS: To date, 29 patients have
      experienced local recurrences and 2, neck metastases. The 5-year survival rates
      were 65% for patients who underwent surgery, 29% for patients who underwent
      radiotherapy, and 63% for patients who underwent a combination of surgery and
      radiotherapy. Univariate survival analysis showed statistical difference
      according to tumor type (P = .003), bone involvement (P = .002), and tumor stage
      (P < .001). CONCLUSION: Every effort must be undertaken to make an early
      diagnosis and perform radical surgical resection of squamous cell carcinomas in
      the external auditory canal. This study validates the staging system used for
      squamous cell carcinoma of the ear treated with surgery.

PMID- 9236592
TI  - Salvage neck dissection for cervical recurrence of nasopharyngeal carcinoma.
AB  - OBJECTIVE: To evaluate the effectiveness of salvage neck dissection as part of a
      multidisciplinary treatment approach in persistent or recurrent metastatic
      nasopharyngeal carcinoma, after failure of initial radiotherapy at the regional
      site. DESIGN: A retrospective study of 31 patients treated during a 14-year
      period from March 1981 through May 1995, with a maximum follow-up of 152 months.
      Factors evaluated include patients' sex, age, and initial stage of tumor,
      mobility and number of nodal recurrences, surgical and pathological findings, and
      postoperative irradiation. SETTING: Academic tertiary referral center. PATIENTS:
      Twenty-six men and 5 women were studied; one patient had neck dissection to both
      sides of the neck on separate occasions, for a total of 32 operations. All
      patients had pathologically proved nasopharyngeal carcinoma and had been
      previously treated at the primary site and both sides of the neck with definitive
      radiotherapy. INTERVENTION: Patients underwent a radical, modified radical, or
      level I-sparing radical neck dissection. MAIN OUTCOME MEASURE: Surgical
      morbidity, time to recurrence at the regional site, and survival time. RESULTS:
      Clinically, there was a disease predilection of 81% at levels II and V. Surgical
      morbidity was minimal. Regional control was achieved in 20 (65%) of the patients,
      and the overall 5-year survival was 67%. Tumor involvement of the posterior
      triangle musculature and spinal accessory nerve was associated with failure to
      control neck disease. Extracapsular nodal extension correlated with a poor
      survival outcome. CONCLUSION: Control of regional disease by salvage neck
      dissection when radiotherapy has failed is both safe and effective in properly
      selected patients.

PMID- 9236593
TI  - Comparison of cost and function in reconstruction of the posterior oral cavity
      and oropharynx. Free vs pedicled soft tissue transfer.
AB  - OBJECTIVE: To compare the cost and functional results of free and pedicled soft
      tissue reconstruction after posterior oral cavity and oropharyngeal extirpation.
      DESIGN: Retrospective study of 53 consecutive patients undergoing extirpation
      with primary soft tissue reconstruction from January 1, 1991, to December 31,
      1995. Median follow-up was 298 days. SETTING: Academic tertiary care medical
      center. INTERVENTION: Twenty-four patients underwent reconstruction with a
      pedicled pectoralis major myocutaneous flap (PMMF); 29 patients, with a
      fasciocutaneous free flap (FF) (27 radial forearm, 1 lateral arm, and 1
      scapular). MAIN OUTCOME MEASURES: Direct (inpatient hospital resources used and
      monetary costs) and intangible (post-operative complications and function) costs.
      RESULTS: Operative time was longer for FF reconstructions (P = .003), but both
      patient groups had similar intensive care unit and hospital stays. Treatment cost
      for FF reconstructions was $41,122, compared with $37,160 for PMMF
      reconstructions (P = .003). This difference was due to increased professional
      fees for FF reconstruction (P < .001) which was offset by intangible cost
      differences. The PMMF group tended toward an increased rate of flap-related
      complications, compared with the FF group. At last follow-up, 4 patients in the
      FF group (15%) and 3 in the PMMF group (15%) had their tracheotomy. In contrast,
      17 (85%) patients in the PMMF group and 11 (39%) patients in the FF group
      required enteral tube feedings (P = .002). Also, 18 (64%) patients in the FF
      group were eating at least a soft diet compared with 6 (30%) patients in the PMMF
      group (P = .02). CONCLUSIONS: Comparison of direct costs reveals only a modest
      difference in reconstruction costs that is outweighed by the intangible costs of
      PMMF reconstruction. The functional benefits of FF reconstruction appear to
      justify its slight increased expense and its use rather than PMMF reconstruction
      after extirpation in the posterior oral cavity and oropharynx.

PMID- 9236594
TI  - Prognostic factors and outcome in craniofacial surgery for malignant cutaneous
      tumors involving the anterior skull base.
AB  - BACKGROUND: We retrospectively reviewed the medical charts of 57 patients with
      advanced malignant cutaneous tumors involving the anterior skull base who
      underwent combined craniofacial resection in our department from January 1, 1981,
      to December 31, 1994. METHODS: The data regarding histological results,
      demographic aspects, clinical presentation, previous treatment, extent of the
      disease, extent of surgical procedure, type of reconstruction, complications, and
      follow-up were analyzed using the chi 2 method. Survival analysis was performed
      using the Kaplan-Meier method. RESULTS: We found prevalence of the male sex (60%)
      and white race (86%), with a mean age of 62 years. Thirty-five patients (61%)
      showed extensive lesions directly invading the anterior skull base (type II); 46
      patients (81%) had been treated previously; 10 patients (18%) had dural invasion;
      29 patients (51%) could not have the eyeball preserved; 32 patients (56%)
      underwent microsurgical reconstruction; and 45 patients (79%) underwent
      pericranial or galeal-pericranial flap reconstruction for the anterior skull base
      defect. Postoperative complications occurred in 29 patients (51%). The most
      common complication was postoperative infection (17 patients [59%]). Thirty-two
      patients (56%) were free of disease, and 4 (7%) were alive with disease at the
      time of our study. CONCLUSIONS: The extent of facial disease (P = .005) and the
      type of facial reconstruction (P = .01) were the most important risk factors in
      the development of infectious complications. Invasion of the dura and the type of
      reconstruction of the anterior skull base were the most important factors related
      to cerebrospinal fluid leakage (P = .003) and meningoencephalitis (P = .06).
      Invasion of the dura mater significantly affected survival (P = .005).

PMID- 9236595
TI  - Prevention of seromas and hematomas after face-lift surgery with the use of
      postoperative vacuum drains.
AB  - OBJECTIVE: To evaluate the rate of hematoma and seroma formation in a series of
      rhytidectomies performed with and without the use of intrawound vacuum drains.
      DESIGN: Retrospective chart review of 222 consecutive face-lifts performed by a
      single surgeon using an identical surgical technique before and after the use of
      vacuum wound drains. The patients were divided into 2 groups of 111 patients
      each. Group 1 patients underwent surgery without drains, while group 2 patients
      had suction drains placed at the time of surgery. MAIN OUTCOME MEASURE: The
      occurrence of seromas and hematomas within the first 24 hours after surgery.
      RESULTS: In group 1, 41 patients (37%) developed seromas and 9 (8%) developed
      hematomas; the hematomas were small and were treated by aspiration alone. In
      group 2, 17 patients (15%) developed seromas and 8 (7%) developed hematomas. The
      decrease in the rate of seroma occurrence was statistically significant, while
      the decrease in hematoma formation did not reach statistical significance.
      CONCLUSIONS: The use of intrawound vacuum drains during the first 24 hours after
      surgery significantly decreases the rate of seroma formation. The occurrence of
      hematomas is also reduced, but less dramatically.

PMID- 9236596
TI  - Air pollution in relation to allergic and nonallergic rhinitis.
AB  - OBJECTIVE: To investigate the relationship between allergic and nonallergic
      rhinitis and the exposure to air pollution. DESIGN: Blood cadmium levels were
      measured in 30 patients with allergic rhinitis, 30 patients with nonallergic
      rhinitis, and 16 normal control subjects using atomic absorption
      spectrophotometry. The cadmium level was used as a parameter of degree and
      proximity of exposure to air pollution from various sources. SETTING: Ain Shams
      University, a tertiary care referral center in Cairo, Egypt. RESULTS: Blood
      cadmium levels were significantly high in the allergic rhinitis group compared
      with the nonallergic rhinitis and control groups (P < .001). The mean blood
      cadmium level in the nonallergic rhinitis group was higher than that in the
      controls, yet the difference was statistically insignificant. Also, cadmium
      levels were above the 95% confidence interval in only 7% of this group. Blood
      cadmium levels in the controls (16.33 +/- 2.98 [SD] micromol/L [183.62 +/- 33.5
      micrograms/dL) were much higher than those reported from areas of high cadmium
      pollution (0.88-2.66 micromol/L [10-30 micrograms/dL]). CONCLUSION: The
      significantly high blood cadmium levels in patients with allergic rhinitis may
      reflect a causal relationship between air pollution and this condition. The exact
      mechanism, however, remains to be determined. In nonallergic rhinitis, it seems
      that the contribution of air pollution as a predisposing factor is small compared
      with the other known predisposing factors.

PMID- 9236597
TI  - Prophylactic antibiotics for posttraumatic cerebrospinal fluid fistulae. A meta
      analysis.
AB  - OBJECTIVE: To determine the efficacy of prophylactic antibiotics in the treatment
      of posttraumatic cerebrospinal fluid fistulae. DESIGN: Meta-analysis with
      literature review. METHODS: A MEDLINE search was performed to obtain all the
      reports pertaining to posttraumatic cerebrospinal fluid fistulae between 1970 and
      1995. All the series that provided data specifying whether prophylactic
      antibiotics were provided and the incidence of the meningitis were included in
      the analysis. RESULTS: The findings of 6 studies, involving 324 patients, were
      analyzed. In these studies, 237 received prophylactic antibiotics and 87 did not.
      Only 6 of the 237 patients who received prophylactic antibiotics developed
      meningitis, yielding an incidence of 2.5%. Nine (10%) of the 87 patients who did
      not receive prophylactic antibiotics developed meningitis. The incidence of
      meningitis was significantly lower in the patients who received prophylactic
      antibiotics than in those who did not receive prophylaxis (Fisher exact test, P =
      .006). CONCLUSIONS: Individually, each of the studies included in this analysis
      demonstrated no significant difference in the incidence of meningitis with
      prophylactic antibiotic therapy. The reason for this is that inadequate numbers
      of patients were available at each institution. Pooling the data from the past 25
      years revealed a statistically significant reduction in the incidence of
      meningitis with prophylactic antibiotic therapy.

PMID- 9236598
TI  - Suspended circummandibular wire fixation for mixed-dentition pediatric mandible
      fractures.
AB  - OBJECTIVE: To introduce and evaluate the technique of cirummandibular wires with
      piriform rim suspension (CMW-PRS) combined with arch bars and a fracture site
      bridle in the treatment of mixed-dentition pediatric mandible fractures. DESIGN:
      Five male patients (mean age, 8.2 years [age range, 7-10 years]) with an isolated
      mixed-dentition mandible fracture were treated with the CMW-PRS technique at the
      University of Texas Health Science Center, San Antonio, from 1985 to 1987 and at
      the University of Missouri, Columbia, from 1992 to 1995. Clinical and
      radiographic fracture healing, somatosensory status, and complications were
      evaluated. RESULTS: All patients demonstrated clinical union to their preinjury
      occlusion by 3 or 4 weeks. They remained without complications until they were no
      longer available for follow-up. Panoramic radiographs supported the findings of
      clinical examinations throughout the study, and no radiographic abnormalities
      were found. There were no somatosensory disturbances of the lingual or
      mental/inferior alveolar nerves. One patient required a tracheostomy unrelated to
      the procedure. CONCLUSION: The CMW-PRS technique combined with arch bars and a
      fracture site bridle wire achieved equivalent historical results when compared
      with the dental splint. The potential advantages and disadvantages of the CMW-PRS
      technique compared with those of monocortical bone plating, as well as the
      significant advantages of the CMW-PRS over the dental splint, are discussed in
      the text.

PMID- 9236599
TI  - Pasteurella multocida epiglottitis.
AB  - Pasteurella multocida, a small gram-negative coccobacillus, colonizes the
      nasopharynx and gastrointestinal tract of many animals, including cats and dogs.
      Most human infections with P multocida are due to animal bites, but the
      respiratory tract is the second most common site of infection. We describe the
      third case report (to out knowledge) of acute P multocida epiglottitis. The mode
      of transmission in this case was inhalation of infectious nasopharyngeal
      secretions from cats. The patient responded well to treatment with penicillin,
      the drug of choice for P multocida infections. Therefore, infection with P
      multocida, though rare, should be considered in the differential diagnosis in any
      case involving acute epiglottitis and exposure to cats.

PMID- 9236600
TI  - Imaging quiz case 1. Posterior fossa arachnoid cyst.

PMID- 9236601
TI  - Imaging quiz case 2. Facial nerve hemangioma.

PMID- 9236602
TI  - Meniere disease.

PMID- 9236603
TI  - The aetiology and management of hepatic metastases.
AB  - Hepatic metastases are a common event in the metastatic spread of primary tumours
      and indicate advanced disease. However, the presence of hepatic metastases does
      not necessarily imply incurability; in selected patients resection of hepatic
      metastases may result in 5-year survival rates of 25-35%, usually in patients
      with colorectal liver metastases in whom solitary metastases are more frequent
      than with other primary tumours. However, hepatic metastases from Wilm's tumours,
      adrenal tumours, renal cell carcinoma, and neuroendocrine tumours may also be
      resected with similar success rates. A poor prognosis after resection of hepatic
      metastases is likely when there are more than three metastatic deposits, involved
      resection margins (often as a result of 'wedge' resections), when there is
      extrahepatic disease, or nodal involvement at the primary tumour site. Cyto
      reductive procedures may provide excellent palliation and possibly long-term
      survival in selected patients with hepatic metastases unsuitable for resection.
      However, further study is required to establish the appropriate role for these
      treatments.

PMID- 9236604
TI  - Biologic implications of genetic changes in head and neck squamous cell
      carcinogenesis.
AB  - Cytogenetic techniques for the analysis of genetic changes common in head and
      neck squamous cell carcinogenesis show complex patterns of chromosomal deletions,
      translocations, and amplifications. Powerful molecular biologic techniques have
      recently made possible the investigation of these abnormalities at the DNA level.
      Tumour suppressor gene loss and oncogene activation can now be recognized in
      tumours. Multiple genetic loci are implicated in the carcinogenesis process,
      while much evidence points to the existence of yet to be recognized tumour
      suppressor genes. An overview of the genetic changes commonly seen in head and
      neck squamous cell carcinogenesis and the possible implications of these are
      presented.

PMID- 9236605
TI  - How accurate are references in the Australian and New Zealand Journal of Surgery?
AB  - BACKGROUND: The accuracy of reference citations in The Australian and New Zealand
      Journal of Surgery was evaluated. All of the references from 1995 (Volume 65)
      were included (n = 4092). METHODS: A sample of 100 references was randomly
      selected and examined in detail by comparison with the original references.
      RESULTS: Overall, 60% of citations contained errors. Errors were categorized by
      dividing references into six elements. A total of 38.8% of citations contained an
      error in one element, 15.6% contained errors in two elements, 4.4% contained
      errors in three elements, and 4.4% contained errors in four elements of the
      reference. The most common errors were errors of authors' names and errors in the
      title. CONCLUSIONS: Contributors to this journal should take more care in
      checking references in the manuscripts before publication.

PMID- 9236606
TI  - A community-based hospital experience with colorectal cancer.
AB  - BACKGROUND: Survival figures for patients with colorectal cancer are often based
      on data from tertiary referral centres for colorectal surgery. The relevance of
      such data to community-based hospitals is questionable. The aim of the present
      study was to determine the long-term survival in patients presenting with
      colorectal cancer to a large community-based teaching hospital. METHODS: A search
      was conducted on the hospital computerized database to determine those patients
      who were admitted with a diagnosis of colorectal cancer between 1989 and 1994.
      These records were linked to the Deaths Registry to determine long-term survival.
      RESULTS: A total of 477 patients were managed at Fremantle Hospital over the 5
      year period. Nearly half of these patients (47.6%) presented via the hospital
      emergency centre. At diagnosis, 57.8% of patients had advanced cancers with
      either nodal or distant metastases. Surgery was undertaken on 455 patients, with
      a postoperative mortality of 4.5%. The corrected 5-year survival rate for
      patients undergoing curative resections (i.e. complete local excision and no
      evidence of metastases) was 62.9% for colon cancers and 48.2% for rectal cancers.
      Local recurrence developed in 21.4% of patients with rectal cancers. CONCLUSIONS:
      A majority of patients with colorectal cancers are continuing to present with
      advanced disease. Earlier diagnosis of these cancers through community-based
      screening programmes could well serve as an achievable solution to this problem.

PMID- 9236607
TI  - Percutaneous microcoil embolization of intraperitoneal intrahepatic and
      extrahepatic biliary fistulas.
AB  - BACKGROUND: Persistent intraperitoneal biliary fistulas are associated with
      significant morbidity and mortality. Percutaneous drainage, stenting, and
      endoscopic sphincterotomy or embolization of biliary radicals have largely
      replaced the need for hepatic resection or biliary reconstruction in managing
      such fistulas. When endoscopy is contraindicated, a previously undescribed
      technique of percutaneous embolization of intrahepatic and extrahepatic biliary
      fistula following penetrating liver trauma, and orthotopic liver transplant and
      its application in three patients, will be discussed. METHODS: Embolization
      procedures were performed by an interventional radiologist. Percutaneous trans
      hepatic cholangiography via a standard right-side approach or via tube
      cholangiography was initially performed and the fistula defined. Coaxial catheter
      systems were used (5 Fr angiography catheters and Tracker 18 infusion catheters),
      and were positioned within the biliary tree as close as possible to the origin of
      the fistula. Embolization was performed using vascular Embolization 28 coils (WA
      Cook) 2-3 mm x 2 cm coils, straight Hilal 18 embolization coils (WA Cook) 5-7 cm,
      as well as Gelfoam (Upjohn) 1 mm pellets, and Histoacryl (B. Braun) 0.25-1 mL.
      Occlusion of the duct was confirmed by a selective intrahepatic cholangiogram. In
      cases of multiple fistulas several embolizations were performed at subsequent
      procedures. Follow-up is over 13 months without adverse event. RESULTS: The
      technique was used in the three cases and was successful in all. A peripheral
      biliary fistula required embolization twice and two cystic leaks were cured after
      a single attempt. CONCLUSIONS: Percutaneous embolization of biliary fistulas
      provides a management option in cases where conservative treatment has failed and
      other techniques are relatively contraindicated. The technique is effective and
      safe in skilled hands, and avoids major surgery. The long-term effect of
      microcoils in the biliary tree is unknown.

PMID- 9236608
TI  - Cosmesis following complete local excision of breast cancer.
AB  - BACKGROUND: With the establishment of the safety of breast conservation in early
      breast cancer, cosmesis has become an increasingly important end-point of
      treatment. The aim of the present study was to establish a model to assess breast
      cosmesis after complete local excision and to assess cosmesis achieved in
      patients who had surgery using the seroma technique. METHODS: A total of 42
      patients were retrospectively reviewed and assessed by independent clinical
      assessment by a surgeon, structured questionnaire and clinical photography.
      RESULTS: A total of 86% of patients were rated by surgeon and patient as having a
      good or excellent cosmetic outcome. There was a high degree of concordance
      between independent clinical assessment and clinical photographic analysis.
      CONCLUSIONS: A model has been established for the assessment of breast cosmesis;
      the technique of seroma formation without reconstruction of the defect results in
      good or excellent cosmesis in the majority of patients.

PMID- 9236609
TI  - The initial Australian experience of technetium-99M sestamibi scintimammography:
      a complementary test in the management of breast cancer.
AB  - BACKGROUND: The adjunctive role of Tc-99m sestamibi scintimammography in the
      diagnosis and management of patients with a high probability of breast cancer was
      assessed. METHODS: A descriptive study of 16 patients with palpable masses who
      had a high probability of breast cancer as determined by investigations such as
      cytology and conventional imaging techniques were carried out. All patients were
      followed-up to surgery. RESULTS: Scintimammography true positive results were
      found in 14 of 18 lesions detected in 16 patients. There were two false-positives
      which included one lobar carcinoma in situ lesion and one complex sclerosing
      lesion, and one false-negative patient. Scintimammography detected abnormal
      radiotracer uptake in four of six patients with axillary metastases. Three
      patients had clinically and mammographically undetected multicentric disease
      detected on scintimammography which allowed appropriate modification of surgical
      excision. Breast cancer was detected in a patient with breast prostheses.
      CONCLUSIONS: Scintimammography would appear to have a useful adjunctive role to
      mammography in the diagnosis of breast cancer. The diagnosis of breast cancer may
      be enhanced in difficult cases and the detection of multicentricity on
      scintimammography may have an impact on subsequent surgical management.

PMID- 9236610
TI  - Fine-needle aspiration biopsy of parotid lesions: comparison with frozen section.
AB  - BACKGROUND: Opinions vary as to the necessity for fine-needle aspiration biopsy
      (FNAB) in parotid tumours. The present study reflects the experience gained over
      a 12-year period and shows the accuracy of a diagnostic FNAB, and improved
      results with experience. METHODS: Between 1983 and 1995, 201 parotid lesions were
      excised by one surgeon(AGP) and a prospective database was established. Fine
      needle aspiration biopsy was performed prior to surgery in 195 lesions and frozen
      section was performed in 159 lesions. RESULTS: The FNAB was diagnostic in 129
      (66%) specimens and its sensitivity for malignancy was 90% and specificity was
      100% (excluding non-diagnostic FNAB, where there was insufficient cellular
      material for reliable diagnosis or where specific tissue diagnosis could not be
      given). The positive predictive value was 100% and the negative predictive value
      was 98%. Of interest, the positive predictive value of diagnostic FNAB for
      pleomorphic adenomas was 99%. A specific tumour diagnosis could not be made on
      the FNAB sample in 37 specimens; 11 of these lesions were histologically
      confirmed as malignant after excision. Frozen section was diagnostic in 144
      specimens (91%). Its sensitivity for malignancy was 96% and specificity was 99%.
      The positive predictive value was 96% and negative predictive value 99%. A
      specific tumour diagnosis could not be made on frozen section in 15 specimens
      including six cases in which malignancy was finally reported. The positive
      predictive value of diagnostic frozen section for pleomorphic adenomas was 99%.
      CONCLUSIONS: A diagnostic FNAB is an accurate and useful tool in the management
      of parotid lesions. An FNAB diagnosis of pleomorphic adenoma obviates the need
      for frozen section. The performance of FNAB in parotid tumours does not in any
      way preclude the necessity of surgical removal of such lesions except in
      exceptional circumstances.

PMID- 9236611
TI  - Hypothermic ischaemia of the liver: a re-perfusion phenomenon.
AB  - BACKGROUND: The effects of hypothermic injury to the liver were investigated on
      an isolated perfusion circuit by comparing porcine livers with varying degrees of
      preservation injury. METHODS: A group of unstored livers (n = 5) were compared to
      livers stored in University of Wisconsin (UW) solution for 18 h (n = 5), and a
      group of livers stored in Hartmann's solution for 18 h (n = 5). RESULTS: We
      observed that the degree of platelet sequestration was directly related to the
      severity of the preservation injury. After 2 h of isolated liver perfusion, the
      perfusate platelet count fell from 148 +/- 14 x 10(9)/L to 84 +/- 13 x 10(9)/L
      for control livers. In comparison for livers stored in UW solution, the platelet
      count fell from 173 +/- 43 x 10(9)/L to 61 +/- 14 x 10(9)/L representing a 64.8%
      fall, while for those stored in Hartmann's solution, an even more profound fall
      from 152 +/- 36 x 10(9)/L to 19 +/- 9 x 10(9)/L (87.5% fall) was observed. The
      difference between the UW-stored and Hartmann's-stored livers was significant (P
      < 0.05). However, using this model, the degree of leukocyte sequestration did not
      differentiate the groups. Both histological and ultrastructural examination of
      liver biopsies taken immediately following revascularization demonstrated that
      for mild degrees of preservation injury following hypothermic storage, changes
      occur to the sinusoidal lining cells well before changes to the parenchymal
      elements. CONCLUSIONS: These findings substantiate the hypothesis that the
      primary injury associated with hypothermia involves the sinusoidal lining cells
      (non-parenchymal elements), that it is predominantly a reperfusion phenomenon and
      that efforts at improving preservation should therefore be targeted primarily at
      these cells and not the hepatocytes.

PMID- 9236612
TI  - The effect of arterial clamp duration on endothelial injury: an experimental
      study.
AB  - BACKGROUND: Arterial clamp-related endothelial damage was investigated in an
      animal model to quantify the surface area of endothelial disruption. The
      influence of the duration of clamp application on this damage was evaluated.
      METHODS: Four identical angled DeBakey vascular clamps were applied on each of
      eight carotid arteries in four heparinized adult sheep for durations of 15, 30,
      45 and 60 min. The applied clamping forces were measured and kept constant. After
      the last clamp was removed, the areas of endothelial loss were identified by in
      vivo staining with Evan's blue dye. The vessels were excised and the blue stained
      areas measured by computer-assisted analysis. The morphological appearance of the
      specimens was assessed by scanning electron microscopy. RESULTS: Endothelial
      damage following clamping for 15 min (10.6 +/- 4.3 mm2) was significantly less
      than for 30 min (19.0 +/- 4.7 mm2), 45 min (19.8 +/- 4.6 mm2) and 60 min (20.4 +/
      4.9 mm2, P = 0.005), but there were no significant differences between the areas
      of endothelial loss observed for 30, 45, and 60 min. These results corresponded
      to the damage seen using scanning electron microscopy, which showed partial
      disruption of endothelium at 15 min compared to more complete destruction at
      longer durations. CONCLUSIONS: Evan's blue staining combined with computer
      assisted surface area measurement is an accurate method for quantifying
      endothelial damage. The extent of damage caused by vascular clamps is partly time
      dependent, being less for 15 min than for 30 min of clamping, but not
      significantly increasing for durations greater than 30 min.

PMID- 9236613
TI  - The lower trapezius island myocutaneous flap for reconstruction of soft tissue of
      the lateral skullbase and neck.
AB  - BACKGROUND: The lower trapezius island myocutaneous flap (LTIMF) has been
      described as a method of reconstruction after excision of carcinoma of the head
      and neck. A high rate of failure and confusion regarding the nomenclature of its
      vascular supply has been reported in the literature. METHODS: The data on six
      patients whose lateral skullbase and upper neck were reconstructed with an LTIMF
      were assessed prospectively. RESULTS: There was one major flap loss, and one
      previously irradiated patient had a minor dehiscence. One patient had a small
      haematoma at the donor site. All wounds were closed primarily and preservation of
      the accessory nerve to the superior fibres of the trapezius muscle enabled almost
      normal abduction of the arm. CONCLUSIONS: The anatomy and complications of the
      LTIMF are reviewed and certain recommendations are made to improve its
      reliability.

PMID- 9236614
TI  - Colorectal diseases.

PMID- 9236615
TI  - Teaching normal physical examination in a large-group interactive using artists'
      models.
AB  - BACKGROUND: The innovative use of artists' models within the context of a large
      group interactive teaching session, at Royal North Shore Hospital is reviewed.
      METHODS: The models were used to teach normal physical examination skills to a
      group of junior medical students, during their surgical rotation. This same group
      of students were also exposed to traditional bedside tutorials. The students
      evaluated both teaching experiences. RESULTS: In the four areas of evaluation
      (interaction, explanation, presentation, and organization), the large-group
      interactive sessions were consistently rated higher than the bedside tutorial (P
      < 0.001). CONCLUSIONS: The teaching technique is presented as an effective way of
      delivering quality clinical training to a group of junior medical students in an
      environment where access to good teaching material is becoming increasingly
      difficult.

PMID- 9236616
TI  - The papal contribution to the development of modern medicine.

PMID- 9236617
TI  - Breast cancer: current issues in diagnosis and treatment.

PMID- 9236618
TI  - Intracranial juvenile nasopharyngeal angiofibroma.
AB  - Eight cases of intracranial extensions of juvenile nasopharyngeal angiofibromas
      (JNA) are presented. These form 33% of the cases of JNA treated during a 5-year
      period (1988-93). A high incidence of visual complications in this stage of
      tumour is observed and the basis of this is discussed. Death results from serious
      complications of severe haemorrhage and cerebro-spinal fluid leak. The intradural
      intracranial extensions of the tumour warrant careful approach in terms of
      surgery, because of their greater risk for complications during the dissection.

PMID- 9236619
TI  - Aortic intimal sarcoma: a case report.

PMID- 9236620
TI  - Primary intestinal Hodgkin's disease complicating ileal Crohn's disease.
AB  - An unusual primary intestinal lymphoma that occurred as a complication of ileal
      Crohn's disease is presented. Immunohistochemistry confirmed the light
      microscopic diagnosis of Hodgkin's disease (nodular sclerosing), and
      characterized a distinct mucosal nodule as a large-cell anaplastic non-Hodgkin's
      lymphoma. This unusual lymphoma developed while the patient was being treated
      with immunosuppressant medication. The present report is a reminder to clinicians
      of the possibility of occult lymphoma in ileal Crohn's disease.

PMID- 9236621
TI  - Use of magnetic resonance imaging on a large lipoma of the hand: a case report.

PMID- 9236622
TI  - The benefit of postoperative radiotherapy in metastatic basal cell carcinoma.

PMID- 9236624
TI  - Acute transverse myelitis. A localized form of postinfectious encephalomyelitis.
AB  - We analysed the clinical, imaging, electrophysiological, laboratory findings,
      course and prognostic factors in 31 patients with acute transverse myelitis (20
      men and 11 women; mean age, 30 years; range, 18-51 years). All patients were
      assessed for maximal clinical deficit 'deficit score'; pattern-shift visual,
      auditory and somatosensory evoked potentials were measured, CSF was examined, and
      neuroimaging of the spinal cord and brain (MRI or CT myelography) was carried
      out. The myelitis was preceded by febrile illness in 25 (81%) of the patients.
      The site of the lesion was cervical in 11 (36%), upper thoracic in two (6%),
      lower thoracic in 16 (52%). MRI of the spinal cord was abnormal in 10 out of the
      20 patients examined (50%); in the remaining 11 patients, only CT was carried out
      and it was normal in all of them. Somatosensory evoked potentials were abnormal
      in 19 (61%), while pattern-shift visual and brainstem auditory evoked potentials
      were normal in all patients. CSF was abnormal in 94% of patients with
      pleocytosis, increased protein or both. Eighteen patients (58%) had good outcome.
      All patients had monophasic illness. Three variables have emerged as being
      associated with significant worsening of the outcome: (i) abnormal somatosensory
      evoked potentials; (ii) abnormal imaging and (iii) high 'deficit score' at onset.
      Acute transverse myelitis affects a complete segment of the spinal cord, is
      monophasic and represents a localized form of postinfectious acute
      encephalomyelitis.

PMID- 9236623
TI  - Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis.
      A report of 50 cases.
AB  - This is the first large series, comprising 50 patients who suffered a total of
      164 episodes, of pseudomigraine with temporary neurological symptoms and
      lymphocytic pleocytosis (PMP syndrome). Onset of PMP was between the ages of 14
      and 39 years and was most frequent in males (68%). Eight males (24%) and five
      females (31%) had a personal history of migraine. One-quarter had had a viral
      like illness up to 3 weeks prior to the onset of the syndrome. The clinical
      picture consisted of one to 12 episodes of changing variable neurological
      deficits accompanied by moderate-to-severe headache and occasionally fever. The
      headaches were described as predominantly throbbing and bilateral with variable
      duration (mean, 19 h). The mean duration of the transient neurological deficits
      was 5 h. Sensory symptoms were most common (78% of episodes), followed by aphasic
      (66%) and motor (56%) symptoms. Visual symptoms appeared in only 12% of episodes.
      The most frequent combinations were motor aphasia plus sensory and motor right
      hemibody symptoms (19% of episodes), motor aphasia plus right sensory symptoms
      (10%) and isolated right (9%) or left (9%) sensory symptoms. All patients were
      asymptomatic between episodes and following the symptomatic period (maximum
      duration 49 days). Lymphocytic pleocytosis ranged from 10 to 760 lymphocytic
      cells/mm3 CSF (mean, 199). In CSF, protein was increased in 96% of patients, IgG
      was normal in 80% of cases and oligoclonal bands were not found. Adensoine
      deaminase values were slightly above normal in two out of 16 patients tested.
      Extensive microbiological determinations, including viral HIV and borrelia
      serologies, were negative. Brain CT and MRI were always within normal limits,
      while EEG frequently showed focal slowing. Conventional cranial angiography was
      performed on 12 patients. In only one were there abnormalities suggestive of
      localized vascular inflammation, coincident with the focal neurological symptoms.
      Two patients developed PMP symptoms immediately after angiography. SPECT,
      performed on only three patients in the symptomatic period, revealed focal areas
      of decreased uptake consistent with the clinical symptoms. PMP aetiology remains
      a mystery; chronic arachnoiditis, viral meningoencephalitis or migraine are not
      plausible aetiological explanations. Because a number of patients had had a
      prodromic viral-like illness, we hypothesize here that such a viral infection
      could activate the immune system, thereby producing antibodies that would induce
      an aseptic inflammation of the leptomeningeal vasculature, possibly accounting
      for this clinical picture.

PMID- 9236625
TI  - Exogenous gangliosides and Guillain-Barre syndrome. An observational study in the
      local health district of Ferrara, Italy.
AB  - A retrospective study was carried out in the Ferrara Local Health District,
      Italy, for the period 1981-1993 (average resident population: 177,235
      inhabitants) to establish whether people exposed to exogenous gangliosides had a
      higher risk of Guillain-Barre syndrome. The incidence of Guillain-Barre syndrome
      of 1.9/100,000 population/year [95% confidence interval (CI): 1.3-2.5] reported
      in Ferrara Local Health District in the same period was used as a reference for
      comparison. The data bank of Ferrara Local Health District made it possible,
      first to estimate the number of individuals exposed to gangliosides in the
      resident population of Ferrara Local Health District (3.7%), the number of
      ganglioside prescriptions and the number of cases of Guillain-Barre syndrome who
      had treatment with gangliosides (nine patients, 20.9%), and, secondly, to verify
      the sequence of events between the ganglioside injection and the onset of the
      disease. Seven of the nine patients (77.8%) received gangliosides as treatment
      for peripheral neuropathy (Guillain-Barre syndrome onset before gangliosides were
      prescribed). For the other two patients (22.2%) a possible appropriate temporal
      sequence between ganglioside injection and onset of Guillain-Barre syndrome was
      found. Based on two possible ganglioside-related cases, the risk of Guillain
      Barre syndrome was higher in the exposed (0.53/100,000 population/month following
      ganglioside injection; 95% CI: 0.06-1.91) compared with the unexposed population,
      but the difference was not significant. When only individuals prescribed with
      mixed gangliosides were considered (both possible ganglioside-related Guillain
      Barre syndrome cases received mixed gangliosides), the risk of Guillain-Barre
      syndrome was higher (0.64/100,000 population/month following ganglioside
      injection; 95% CI: 0.08-2.31) but the difference from the risk in unexposed
      individuals was not statistically significant. The relative risk for the exposure
      to mixed gangliosides was borderline (relative risk = 4.3; 95% CI: 1.0-17.8). The
      wide 95% confidence intervals were a consequence of sample size limitations.
      Considering also that the exposed and unexposed groups differed in age (those
      exposed were older than those unexposed and the age-specific incidence of
      Guillain-Barre syndrome in the study population increased with increasing age),
      the present findings question either a strong increased risk of Guillain-Barre
      syndrome in people exposed to exogenous gangliosides or an immunogenic role of
      these agents in humans. However, because of the limited sample size, the results
      are not conclusive.

PMID- 9236626
TI  - Local human sural nerve blood flow in diabetic and other polyneuropathies.
AB  - Microangiopathy is considered relevant to the pathogenesis of several forms of
      peripheral nerve disease, particularly diabetic polyneuropathy. In diabetes,
      however, it is uncertain whether reductions in mixed nerve trunk blood flow
      account for early features of polyneuropathy in contrast to later disease, where
      microvascular changes have been described. To address this issue, we measured
      local sural nerve blood flow in patients with mild diabetic polyneuropathy who
      were enrolled in a clinical trial (n = 26), patients with other polyneuropathies
      being studied by diagnostic sural nerve biopsy (n = 17), patients with vasculitic
      polyneuropathy (n = 3) and one patient with rapidly progressive severe diabetic
      polyneuropathy and lumbosacral plexopathies. Standardized measurements were made
      at 10 sites along the sural nerve of each patient prior to sural nerve resection
      for biopsy. We used a laser Doppler flowmetry probe sensitive to red blood cell
      flux to measure sural nerve blood flow. This was slightly higher in patients with
      mild diabetes compared with those with other polyneuropathies, but was reduced in
      patients with vasculitis. In patients with mild diabetes, there was no
      relationship between sural nerve blood flow and prebiopsy sural nerve action
      potential amplitude, sural myelinated fibre density, haemoglobin A1C, duration of
      diabetes or age of the patient. Ten diabetic patients entered in the clinical
      trial had sural nerve blood flow recorded in one sural nerve, followed 1 year
      later by a second sural nerve blood flow measurement prior to biopsy of the
      contralateral sural nerve. Despite a mild trend toward decline in fibre density
      between the nerves over this period of time, sural nerve blood flow was similar.
      The patient with severe diabetic polyneuropathy and lumbosacral plexopathies had
      reduced sural nerve blood flow. Our findings do not provide evidence that
      reductions in sural nerve blood flow are associated with early peripheral
      neuropathy in diabetes, unlike vasculitis. The early trend toward slight rises in
      sural nerve blood flow may be a result of early functional microangiopathy that
      accompanies nerve dysfunction but does not cause it.

PMID- 9236627
TI  - Neurophysiological abnormalities in adrenoleukodystrophy carriers. Evidence of
      different degrees of central nervous system involvement.
AB  - We studied 19 women, heterozygous for adrenoleukodystrophy (ALD) in whom the
      carrier status was demonstrated by abnormally high plasma levels of very-long
      chain fatty acids. Clinical examination revealed slight neurological signs in two
      patients. Clear-cut neurological deficits in three, and it was fully normal in
      the remaining 14. All subjects underwent motor evoked potential (MEP) and
      somatosensory evoked potential (SEP) studies. Seventeen out of 19 subjects
      underwent brain MRI which demonstrated various degrees of abnormality in one
      asymptomatic and five symptomatic subjects; SEPs and MEPs revealed CNS
      involvement in 12 and 8 out of the 19 subjects, respectively. Symptomatic
      patients showed severe neurophysiological abnormalities, whereas milder but
      unequivocal EP abnormalities were found in seven of the 14 patients with normal
      clinical examination. Our data thus suggest CNS involvement in the majority of
      the ALD carriers, evident also in preclinical stages and progressively severe.
      The possibility of assessing different degrees of neurological involvement could
      be relevant for therapeutical purposes. Moreover, neurophysiological studies
      could provide the only objective marker of functional nervous system involvement,
      e.g. in order to monitor the efficacy of treatment, and in clinically and
      radiologically silent cases.

PMID- 9236628
TI  - Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium
      dose, magnetization transfer contrast and delayed imaging.
AB  - Although clinical end points remain the definitive measure of therapeutic
      efficacy in multiple sclerosis, more sensitive markers of disease activity are
      required to screen potential disease-modifying agents. The use of gadolinium
      contrast-media in MRI studies increases both the reliability and sensitivity of
      detecting active lesions in multiple sclerosis. We studied three potential
      methods for further improving sensitivity; the use of 0.3 mmol/kg (triple dose)
      gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), magnetization transfer
      (MT) contrast imaging and the introduction of a delay between contrast-medium
      injection and imaging. Fifty patients were studied (seven with benign, 14 with
      relapsing-remitting, 10 with secondary progressive, 16 with primary progressive
      and three with transitional multiple sclerosis). Imaging was performed on two
      occasions, 24-72 h apart, with triple- and single-dose Gd-DTPA. Pairs of contrast
      enhanced T 1-weighted studies, with and without MT, were obtained at three
      different times, i.e. within early (0-20 min), short-delay (20-40 min) and long
      delay (40-60 min) time-windows. Nineteen patients did not have the full
      complement of studies. Seven patients suffered minor self-limiting adverse events
      possibly related to triple-dose Gd-DTPA. Overall, triple-dose Gd-DTPA resulted in
      a 75% increase in the number of enhancing lesions detected compared with the
      single dose (P < 0.002). The use of MT or delay alone did not significantly
      increase the sensitivity of either single- or triple-dose studies. The
      combination of MT and short delay increased the number of enhancing lesions
      detected with single-dose Gd-DTPA by 47% (P < 0.05) and with triple-dose Gd-DTPA
      by 27% (P < 0.01). Detection was not significantly further improved by a long
      delay. The most sensitive modality was MT imaging with a long delay following
      triple-dose Gd-DTPA, resulting in the detection of 126% more enhancing lesions
      than in standard single-dose imaging (P < 0.05). This applies to all subgroups
      except for primary progressive multiple sclerosis, in which none of these methods
      alone or in combination improved the sensitivity. We conclude that for relapsing
      remitting and secondary progressive multiple sclerosis, the combination of triple
      dose Gd-DTPA and delayed MT imaging more than doubles the sensitivity to contrast
      enhancing lesions.

PMID- 9236629
TI  - Neglect in vision and visual imagery: a double dissociation.
AB  - We report two patients with right hemisphere lesions who demonstrate a double
      dissociation on visual imagery and visual perceptual tasks. One (M.N.) performed
      normally on a variety of standard tests for neglects as well as on measures of
      visual attention known to be sensitive to the presence of neglect, yet failed to
      report items from the left side of an imagined scene. In contrast, the other
      (C.I.) performed normally on tests of visual imagery but demonstrated substantial
      neglect on visual perceptual and visual attentional tasks. These data are not
      readily accommodated by accounts which attribute neglect to a single processing
      deficit, but suggest that the disorder is a heterogeneous syndrome attributable
      to disruptions of different aspects of spatial cognition.

PMID- 9236630
TI  - Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET
      study.
AB  - To assess dynamic changes in brain function throughout the sleep-wake cycle, CBF
      was measured with H2(15)O and PET in 37 normal male volunteers: (i) while awake
      prior to sleep onset; (ii) during Stage 3-4 sleep, i.e. slow wave sleep (SWS);
      (iii) during rapid eye movement (REM) sleep; and (iv) upon waking following
      recovery sleep. Subjects were monitored polysomnographically and PET images were
      acquired throughout the course of a single night. Stage-specific contrasts were
      performed using statistical parametric mapping. Data were analysed in repeated
      measures fashion, examining within-subject differences between stages [pre-sleep
      wakefulness-SWS (n = 20 subjects); SWS-post-sleep wakefulness (n = 14); SWS-REM
      sleep (n = 7); pre-sleep wakefulness-REM sleep (n = 8); REM sleep-post-sleep
      wakefulness (n = 7); pre-sleep wakefulness-post-sleep wakefulness (n = 20)].
      State dependent changes in the activity of centrencephalic regions, including the
      brainstem, thalamus and basal forebrain (profound deactivations during SWS and
      reactivations during REM sleep) are consistent with the idea that these areas are
      constituents of brain systems which mediate arousal. Shifts in the level of
      activity of the striatum suggested that the basal ganglia might be more
      integrally involved in the orchestration of the sleep-wake cycle than previously
      thought. State-dependent changes in the activity of limbic and paralimbic areas,
      including the insula, cingulate and mesial temporal cortices, paralleled those
      observed in centrencephalic structures during both REM sleep and SWS. A
      functional dissociation between activity in higher order, heteromodal association
      cortices in the frontal and parietal lobes and unimodal sensory areas of the
      occipital and temporal lobes appeared to be characteristic of both SWS and REM
      sleep. SWS was associated with selective deactivation of the heteromodal
      association areas, while activity in primary and secondary sensory cortices was
      preserved. SWS may not, as previously thought, represent a generalized decrease
      in neuronal activity. On the other hand, REM sleep was characterized by selective
      activation of certain post-rolandic sensory cortices, while activity in the
      frontoparietal association cortices remained depressed. REM sleep may be
      characterized by activation of widespread areas of the brain, including the
      centrencephalic, paralimbic and unimodal sensory regions, with the specific
      exclusion of areas which normally participate in the highest order analysis and
      integration of neural information. Deactivation of the heteromodal association
      areas (the orbital, dorsolateral prefrontal and inferior parietal cortices)
      constitutes the single feature common to both non-REM and REM sleep states, and
      may be a defining characteristic of sleep itself. The stages of sleep could also
      be distinguished by characteristic differences in the relationships between the
      basal ganglia, thalamic nuclei and neocortical regions of interest.

PMID- 9236631
TI  - Mirror movements in X-linked Kallmann's syndrome. I. A neurophysiological study.
AB  - Possible mechanisms underlying the pathological mirror movements that are seen in
      the majority of patients with X-linked Kallmann's syndrome have been investigated
      using neurophysiological techniques. An EMG was recorded from the first dorsal
      interosseous muscle (1DI) during voluntary self-paced abduction of one indexed
      finger; EMG activity could also be recorded simultaneously from the contralateral
      1DI. There was no significant difference between the time of onset of the bursts
      of voluntary and involuntary mirroring EMG. Focal magnetic stimulation of the
      hand area of the motor cortex revealed the presence of fast conducting bilateral
      corticospinal projections from each motor cortex in all subjects. However, both
      inter- and intra-subject differences exist when considering the ratio of
      ipsilaterally to contralaterally projecting axons. Cross-correlation analysis of
      multi-unit EMGs recorded during simultaneous voluntary sustained activation of
      homologous left and right pairs of distal upper limb muscles was performed. A
      short duration central peak was seen in the cross-correlograms indicating the
      presence of a common drive to left and right homologous motor neuron pools. This
      common drive may result from the synchronous activation of intermingled
      ipsilaterally and contralaterally projecting corticospinal neurons in the motor
      cortex. Cutaneomuscular reflexes were recorded from the 1DI following stimulation
      of the digital nerves of the index finger. Typically each reflex comprises spinal
      and longer latency trans-cortical components. In these subjects, the long latency
      components of the reflex response could, in addition, be recorded from the 1DI of
      the non-stimulated side. We conclude that these subject have a novel ipsilateral
      at least in part, for the pathological mirroring.

PMID- 9236632
TI  - Mirror movements in X-linked Kallmann's syndrome. II. A PET study.
AB  - To investigate the mechanism of mirror movements seen in X-linked Kallmann's
      syndrome, we measured changes of regional cerebral blood flow with H2 15O-PET. We
      studied six right-handed Kallmann male subjects and six matched, right-handed
      control subjects during an externally paced finger opposition task. The analyses
      were done both on a single subject and a group basis. The Kallmann group showed a
      strong primary motor cortex (M1) activation contralateral to the voluntarily
      moved hand, but there was also a significant degree of M1 activation ipsilateral
      to the voluntarily moved hand, i.e. contralateral to the mirroring hand. However,
      when comparing contralateral to ipsilateral M1 activation, the M1 activation
      contralateral to the voluntarily moved hand was significantly stronger. In the
      controls, significant increases in rCBF were seen in the contralateral M1 during
      voluntary movement of either hand; a small ipsilateral M1 activation was found in
      two out of six normal subjects when they moved their left hand. In a second
      experiment it was shown that, in two out of two Kallmann subjects, passive
      movements of the right hand resulted in left M1 activation that was similar to
      the activation in the left M1 when subjects made mirror movements with their
      right hand. This suggests, but does not prove, that the small but significant
      activation of the ipsilateral M1 in Kallmann's subjects may be due to sensory
      feedback from the involuntarily mirroring hand.

PMID- 9236633
TI  - Spatial- and object-based attentional deficits in Alzheimer's disease.
      Relationship to HMPAO-SPECT measures of parietal perfusion.
AB  - The purpose of this study was to investigate the ability of patients with
      Alzheimer's disease to shift attention between spatial locations and between
      objects, and to examine the brain regions involved in these cognitive operations
      using single photon emission computed tomography (SPECT) imaging. A recent study
      of patients with focal lesions provided evidence that the right and left parietal
      lobes are differentially involved in shifting selective attention from invalidly
      cued spatial locations and objects, respectively (Egly et al. J Exp Psychol Gen
      1994; 123: 161-77). Accordingly, in Alzheimer's disease patients, we hypothesized
      that right parietal hypoperfusion on SPECT would be associated with deficits on
      the spatial-based component of a cued reaction time task, and left parietal
      hypoperfusion would be associated with the deficits on the object-based
      component. Attentional performance of Alzheimer's disease patients (n = 29) was
      compared with aged-matched normal controls (n = 17) using a cued reaction time
      task based on Egly et. al. (1994). Regions of interest were defined semi
      automatically on SPECT, and were anatomically localized with the aid of co
      registered MRI. As hypothesized, in Alzheimer's disease patients, reaction time
      costs of invalid targets eliciting shifts of attention between spatial locations
      were selectively correlated with SPECT hypoperfusion in the right superior
      parietal lobe; while reaction time costs of between-object shifts of attention
      were correlated with hypoperfusion in the left inferior parietal lobe. These
      results provide evidence for the specialized roles of the right and left parietal
      regions in the spatial and object components of attentional shifting
      respectively, and suggest that the cognitive profile associated with Alzheimer's
      disease includes both spatial- and object-based attentional impairments.

PMID- 9236634
TI  - Potential use of herpes simplex virus (HSV) vectors for gene therapy of
      neurological disorders.
AB  - Advances in molecular biology and virus genetics have allowed the possibility of
      gene therapy using viral vectors for a variety of neurological diseases in which
      the genetic or biochemical basis is understood. A number of such vectors have now
      been constructed, including those derived from herpes simplex virus (HSV),
      adenovirus, retrovirus and adeno-associated virus, and used in preliminary in
      vitro experiments and in animal models. It is possible to package a foreign gene
      into such a vector which can then be targeted to specific regions of the nervous
      system. HSV is particularly appropriate for delivering genes to neurons in view
      of its ability to establish latent infection in these cells. Viral vectors have
      the potential to be used to treat such neurological conditions as malignant
      gliomas, Parkinson's disease, known single gene disorders and cerebral ischaemia.
      However, the technical problems which will need to be overcome are formidable and
      will not be easily solved. The problems include the efficient delivery of the
      vector to target cells, the maintenance and control of foreign gene expression,
      and the control of unwanted host immune responses.

PMID- 9236635
TI  - Paradoxical functional facilitation in brain-behavior research: a critical
      review.

PMID- 9236636
TI  - Randomised controlled trials in perinatal medicine: 1. The need for studies of
      mortality and major morbidity with adequate power.

PMID- 9236637
TI  - Randomised controlled trials in perinatal medicine: 2. Recruitment of a pregnant
      woman or her newborn child into more than one trial.

PMID- 9236638
TI  - Randomised controlled trials in perinatal medicine: 3. Identifying and measuring
      endpoints in randomised controlled trials.

PMID- 9236639
TI  - Obstetric intervention and benefit in conditions of very low prevalence.

PMID- 9236640
TI  - Recombinant human relaxin as a cervical ripening agent.
AB  - OBJECTIVE: The aim of this study was to investigate the efficacy and safety of
      recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an
      unfavourable cervix before induction of labour at term. DESIGN: A multi-centre,
      double-blind, placebo-controlled trial performed in Edinburgh, Glasgow and
      Oxford. Women were treated with 0, 1, 2 or 4 mg of rhRIx in a gel vehicle
      administered intravaginally. Analysis of variance tests were performed on all
      continuous variables, and Cochran Mantel-Haenszel tests employed for all discrete
      variables. PARTICIPANTS: Ninety-six women at 37 to 42 weeks of gestation with a
      singleton pregnancy and a modified Bishop score of < or = 4 were recruited.
      RESULTS: There was no significant difference in the change in modified Bishop
      score between the four treatment groups. The lengths of the first and second
      stages of labour were similar in all 4 groups. PGE2 and oxytocin requirements
      were similar in all groups, as was the mode of delivery. There was no evidence
      that relaxin was absorbed systemically when given in this way. CONCLUSION:
      Recombinant human relaxin 1 to 4 mg, administered as an intravaginal gel, has no
      effect as a cervical ripening agent before induction of labour at term.

PMID- 9236641
TI  - Routine oxytocin in the third stage of labour: a placebo controlled randomised
      trial.
AB  - OBJECTIVE: To compare intravenous oxytocin administration (Partocon 10 IU) with
      saline solution in the management of postpartum haemorrhage in the third stage of
      labour. DESIGN: A double-blind, randomised controlled trial involving 1000
      parturients with singleton fetuses in cephalic presentation and undergoing
      vaginal delivery, randomly allocated to treatment with oxytocin (n = 513) or 0.9%
      saline solution (n = 487). SETTING: Labour ward at a central county hospital.
      MAIN OUTCOME MEASURES: Mean blood loss (total, and before and after placenta
      delivery); frequencies of blood loss > 800 mL, need of additional oxytocic
      treatment, postpartum haemoglobin < 10 g/dL; and duration of postpartum
      hospitalisation. RESULTS: As compared with saline solution, oxytocin
      administration was associated with significant reduction in mean total blood loss
      (407 versus 527 mL), and in frequencies of postpartum haemorrhage > 800 mL (8.8%
      versus 5.2%), additional treatment with metylergometrine (7.8% versus 13.8%), and
      postpartum Hb < 10 g/dL (9.7% versus 15.2%), and a nonsignificant increase in the
      frequency of manual placenta removal (3.5% versus 2.3%). There was no group
      difference in the mean duration of postpartum hospitalisation (4.6 versus 4.5
      days, respectively). CONCLUSIONS: Administration of intravenous oxytocin in the
      third stage of labour is associated with an approximately 22% reduction in mean
      blood loss, and approximately 40% reductions in frequencies of postpartum
      haemorrhage (> 500 mL or > 800 mL) and of postpartum haemoglobin < 10 g/dL.
      Identification of risk groups for oxytocin treatment does not seem worthwhile.
      Oxytocin is a cheap atoxic drug and should be given routinely after vaginal
      delivery.

PMID- 9236642
TI  - Antenatal perineal massage and subsequent perineal outcomes: a randomised
      controlled trial.
AB  - OBJECTIVE: To study the effects of antenatal perineal massage on subsequent
      perineal outcomes at delivery. DESIGN: A randomised, single-blind prospective
      study. SETTING: Department of Obstetrics and Gynaecology, Watford General
      Hospital. PARTICIPANTS: Eight hundred and sixty-one nulliparous women with
      singleton pregnancy and fulfilling criteria for entry to the trial between June
      1994 and October 1995. RESULTS: Comparison of the group assigned to massage with
      the group assigned to no massage showed a reduction of 6.1% in second or third
      degree tears or episiotomies. This corresponded to tear rates of 75.1% in the no
      massage group and 69.0% in the massage group (P = 0.073). There was a
      corresponding reduction in instrumental deliveries from 40.9% to 34.6% (P =
      0.094). After adjustment for mother's age and infant's birthweight these
      reductions achieved statistical significance (P = 0.024 and P = 0.034,
      respectively). Analysis by mother's age showed a much larger benefit due to
      massage in those aged 30 and over and a smaller benefit in those under 30.
      CONCLUSION: Antenatal perineal massage appears to have some benefit in reducing
      second or third degree tears or episiotomies and instrumental deliveries. This
      effect was stronger in the age group 30 years and above.

PMID- 9236643
TI  - Gestational age and induction of labour for prolonged pregnancy.
AB  - OBJECTIVE: To examine the length of gestation according to menstrual and
      ultrasound scan dates, and the rate of induction of labour in a unit with a
      routine induction policy for prolonged pregnancy. DESIGN: Retrospective analysis
      of computer files of 24,675 pregnancies delivered in a teaching hospital between
      1988 and 1995, which had a record of the last menstrual period and a dating
      ultrasound scan. Detailed survey of 168 casenotes of consecutive inductions of
      labour to establish the indications given. SETTING: Teaching hospital with
      policies of routine mid-trimester ultrasound scan and routine induction for
      prolonged pregnancy at 290 to 294 days. MAIN OUTCOME MEASURES: Gestational age at
      delivery by menstrual history and ultrasound biometry in spontaneous and induced
      labours. RESULTS: The single largest category of reasons given for induction of
      labour was prolonged pregnancy. 'Post-term pregnancy', from the date of expected
      delivery as recorded in the notes, together with 'maternal request' and 'social
      factors', were the reasons given for induction of labour in 71.3% of cases.
      Menstrual dates systematically overestimated gestational age at term when
      compared with scan dates. After 41 weeks, this difference exceeded the confidence
      limits for second trimester scan dating error, suggesting that most pregnancies
      which are considered 'prolonged' according to menstrual dates are in fact mis
      dated. The median gestational age for induced labours was 286 days by last
      menstrual period but only 280 days by scan, and most (71.5%) inductions done post
      term (> 294 days) according to menstrual dates were not post-term if scan dates
      alone are used to calculate the gestational age. The average induction rate over
      the seven year study period was 16.6%. It was higher when there was any
      gestational age error in either direction (16.8%) compared with when menstrual
      and scan dates were in complete agreement (13.7%, OR 1.27, CI 1.09-1.47, P <
      0.001). The induction rate was highest (up to 21.8%) in the cases where menstrual
      dates overstated gestational age without exceeding the usual limits for adjusting
      dates according to scan. Such overestimation within tolerance limits of 7, 10 or
      14 days occurred in 37.1%, 45.8%, or 52.6% of all pregnancies, respectively.
      CONCLUSIONS: Most pregnancies undergoing post-term induction are not post-term
      when assessed by ultrasound dates. Regardless of whether prolonged pregnancy is
      considered to be a risk factor requiring intervention, the proportion of
      pregnancies considered 'post-term' can be reduced considerably by a dating policy
      which ignores menstrual dates and establishes the expected delivery date on the
      basis of ultrasound dates alone.

PMID- 9236644
TI  - Predictors of successful external cephalic version at term: a prospective study.
AB  - OBJECTIVE: To investigate clinical and ultrasonographic predictors of outcome of
      external cephalic version at term. DESIGN: Prospective observational study.
      SETTING: University obstetric unit. POPULATION: All external cephalic versions
      performed over two years (n = 243). METHODS: Nineteen different clinical and
      ultrasonographic variables were recorded before each procedure. The ability of
      each of the 19 variables to predict the success or failure of external cephalic
      version was assessed by univariate analysis. The study population was then
      divided into two subgroups of 129 and 114 patients by random allocation using
      computer generated numbers. Logistic regression was performed in each subgroup to
      assess the relative importance and independence of the important variables. The
      derived regression models were then applied to the other subgroup of patients to
      assess accuracy and reproducibility. RESULTS: The overall success rate of the
      procedure was 69.5%. Both regression models identified the same three variables
      as independent predictors of failed versions: 1. presenting part engaged; 2.
      difficult to palpate the fetal head, and 3. a tense uterus on palpation. The two
      models correctly predicted 75.2% and 84.2% of outcomes in the other subgroup. If
      uterine tone, which was assessed after administration of tocolytic, was excluded
      from the analysis, the other two factors remained in the models, with the
      addition of nulliparity as a significant predictor of failed external cephalic
      version. The chance of success of external cephalic version in the original 243
      women was found to be < 20% if two of these variables were present, 0% if all
      three were present, and 94% if none were present. CONCLUSIONS: The outcome of
      external cephalic version can be predicted by easily available clinical
      parameters.

PMID- 9236645
TI  - The obstetric experience of carriers of haemophilia.
AB  - OBJECTIVE: To review the obstetric problems, pregnancy outcome and management of
      carriers of haemophilia. DESIGN: Retrospective review of haemophilia and
      maternity unit records. SETTING: Haemophilia Comprehensive Care Centre.
      PARTICIPANTS: Thirty-two carriers of haemophilia (24 haemophilia A, eight
      haemophilia B) who had their obstetric care at the Royal Free Hospital over a 10
      year period (1985-1995). MAIN OUTCOME MEASURES: Uptake and results of prenatal
      diagnosis, changes in factor levels during pregnancy, effect of knowledge of
      fetal gender on obstetric management and neonatal outcome, and maternal
      haemorrhagic complications. RESULTS: There were 82 pregnancies and 32 resulted in
      miscarriage or social abortion. The option of prenatal diagnosis was taken up in
      only 35% (17/48) of pregnancies. There were five affected male fetuses diagnosed
      prenatally but only three women opted for termination of the pregnancy. Knowledge
      of fetal gender was unavailable to the attending obstetrician in 46% (21/46) of
      pregnancies. A fetal scalp electrode was applied in eight, fetal blood sampling
      was performed in four, and ventouse delivery was conducted in one of these
      pregnancies. No adverse effects were reported from the first two procedures, but
      the ventouse delivery was associated with a huge cephalhaematoma requiring blood
      transfusion. On the other hand, in five cases fetal blood sampling was withheld
      because fetal gender was unknown. Four of the eight caesarean sections performed
      might have been avoided if the gender had been known. The incidence of primary
      and secondary postpartum haemorrhage was high, 22% (including two cases with
      massive haemorrhage) and 11%, respectively. CONCLUSION: Carriers of haemophilia A
      and B require special obstetric care with close liaison with the haemophilia
      centre, and management guidelines should be available and observed. Knowledge of
      fetal gender is very valuable for management in labour and should be determined
      antenatally even if the mother declines prenatal diagnosis.

PMID- 9236646
TI  - Screening for Down's syndrome: changes in marker levels and detection rates
      between first and second trimesters.
AB  - OBJECTIVE: To monitor changes with gestation in levels of alpha-fetoprotein
      (AFP), free beta human chorionic gonadotrophin (F beta hCG) and pregnancy
      associated plasma protein-A (PAPP-A) in Down's syndrome pregnancies and to
      compare risks estimated in the first trimester with those obtained by routine
      screening in the second trimester for the same pregnancies. DESIGN: In each of 47
      Down's syndrome pregnancies two maternal serum samples were obtained, one in the
      first trimester and one in the second trimester. Comparison of marker levels with
      10,600 first trimester controls and a smaller sample of second trimester controls
      allowed case identification criteria based on optimum marker combinations to be
      developed and compared directly between trimesters. SETTING: Biochemical genetics
      laboratory. RESULTS: F beta hCG was an effective marker of Down's syndrome in
      both the first and second trimesters. PAPP-A levels were significantly reduced in
      trisomy 21 pregnancies in the first trimester only. Using a population model,
      these two markers in combination with maternal age gave an overall detection rate
      of 55% for a 5% false positive rate in the first trimester. For the paired first
      and second trimester samples, three of six cases classified as low risk by
      routine second trimester screening were classified as high risk by the first
      trimester screening protocol of F beta hCG/PAPP-A/maternal age. However, fifteen
      cases identified as high risk by routine second trimester screening were
      classified as low risk in the first trimester, a net loss in detection of 12
      cases by first trimester screening. CONCLUSION: The data suggest that first
      trimester detection rates for Down's syndrome using a combination of F beta hCG
      and PAPP-A may vary with gestation and will be lower than those currently
      obtained by routine second trimester screening with AFP/hCG.

PMID- 9236647
TI  - The disappearance of fetal and donor red blood cells in alloimmunised
      pregnancies: a reappraisal.
AB  - OBJECTIVE: To determine the proportional reduction per day in the number of fetal
      and donor red blood cells from the fetal circulation after intrauterine
      intravascular transfusions. DESIGN: A retrospective study of 302 transfusions in
      101 fetuses. SETTING: The Department of Obstetrics and Gynaecology of the
      University Medical Centre Leiden, The Netherlands. METHODS: We measured the
      haematocrit in fetal samples both before and after repeated intravascular
      intrauterine transfusion in fetuses with alloimmune disease. The percentage of
      fetal erythrocytes was determined in Kleihauer-Betke stained smears. The decline
      of fetal, donor and mixed red blood cells was calculated by dividing the
      proportional decrease of the haematocrit values of the number of days between
      transfusions, also after correction for changes in fetoplacental volumes. Results
      (given as mean [SD]) are derived from the proportional changes of haematocrit per
      day. RESULTS: The interval between the first and second transfusion (15.5 days
      [SD 5.2]) was shorter than between subsequent transfusions (means ranging from
      21.4 to 21.9 days; P < or = 0.0001). The decline per day of mixed, and of donor
      red blood cells, calculated without corrections for volume changes did not differ
      from those corrected for volume changes resulting from the transfusion and from
      fetal growth (correction factor 1.1 [SD 0.4]). Since the coefficient of variance
      is smaller for the uncorrected decline values, this type of calculation is
      preferable for clinical purposes. The disappearance of fetal erythrocytes after
      the first transfusion (6.1%/day [SD 2.9]) was faster than that of mixed fetal and
      donor red blood cells (3.2%/day [SD 1.2]; P < 0.0001) and of donor cells alone
      (1.4%/day [SD 1.6]; P < 0.0001). The decline of the mixed red blood cell
      population became the same as that of the donor cells (2.2%/day [SD 0.8]) after
      the second transfusion. This decline of donor cells was higher than after the
      first transfusion (1.4%/day [SD 1.6]; P < 0.05). After the first transfusion the
      fetal erythrocytes disappeared faster after transplacental puncture of the
      umbilical cord (6.6%/day [SD 2.8]) than after transamniotic punctures (5.4%/day
      [SD 2.7]; P = 0.05). The mixed red blood cell also decreased faster (3.5%/day [SD
      1.3] versus 2.8%/day [SD 0.9]; P < 0.01). CONCLUSION: The fast disappearance of
      fetal erythrocytes, especially after transplacental punctures, shows that the
      interval between the first and second transfusion needs to be shorter than that
      for intervals between subsequent transfusions. The number of donor erythrocytes
      declines by approximately 2% per day.

PMID- 9236648
TI  - Circadian rhythm of frequency-domain measures of heart rate variability in
      pregnancy.
AB  - OBJECTIVE: To examine frequency domain measures of heart rate variability and
      their circadian rhythms in pregnancy. DESIGN: A longitudinal study. SETTING:
      University hospital in Turku, Finland. PARTICIPANTS: Sixteen healthy women
      between 11 and 27 weeks of pregnancy; 12 women before pregnancy; and four women
      postpartum. MAIN OUTCOME MEASURES: Heart rate variability as measured in
      frequency domain from 24-hour ambulatory electrocardiography. RESULTS: Pregnancy
      was associated with a lower standard deviation of R-R intervals (P < 0.01), with
      reduced very low (P < 0.05), low (P < 0.01), and high frequency (P < 0.05) power
      spectral components of heart rate variability. The high frequency power was lower
      at night in pregnancy, but similar in the daytime in pregnant and nonpregnant
      women. CONCLUSIONS: Pregnancy is associated with an overall reduction in heart
      rate variability, most markedly reflected in the low frequency component. This
      suggests altered baroreflex or sympathetic modulation of heart rate, and
      decreased vagal activation at night.

PMID- 9236650
TI  - Is conservative surgery for tubal pregnancy preferable to salpingectomy? An
      economic analysis.
AB  - OBJECTIVE: The traditional treatment of ectopic pregnancy is salpingectomy, while
      conservative surgery aims to save the function of the uterine tube. This study
      compares the effectiveness and the economic costs of salpingectomy and
      conservative tubal surgery in women with a tubal pregnancy. METHODS:
      Salpingectomy and conservative tubal surgery were compared economically, based on
      a combined retrospective and prospective cohort study and a review of the
      literature. A model was developed in which conservative surgery and salpingectomy
      with in vitro fertilisation and embryo-transfer (IVF-ET) were compared with
      salpingectomy alone. PARTICIPANTS: One hundred and fifteen consecutive women
      treated laparoscopically for tubal pregnancy. MAIN OUTCOME MEASURES: Complete
      removal of the tubal pregnancy; subsequent intrauterine pregnancy rate; economic
      analysis. RESULTS: Tubal pregnancy was always treated successfully by both
      methods, sometimes with additional treatment for persistent trophoblast. In the
      short term costs per patient were 1554 pounds (95% confidence interval [CI] 1501
      pounds-1656 pounds) for salpingectomy and 1787 pounds (95% CI 1683 pounds-1930
      pounds) for conservative surgery. The mean difference between costs of
      salpingectomy and costs of conservative surgery was 233 pounds (95% CI 80 pounds
      371 pounds). Concerning subsequent intrauterine pregnancy, conservative surgery
      is slightly more effective than salpingectomy but is more expensive. Costs per
      subsequent intrauterine pregnancy are 4063 pounds. If IVF-ET is performed in all
      women who are not pregnant within three years after salpingectomy, costs per
      subsequent intrauterine pregnancy are 15,629 pounds. CONCLUSIONS: Salpingectomy
      is the treatment of choice in women not desiring future pregnancy. Salpingectomy
      seems less effective than conservative surgery when future pregnancy is desired,
      but is less costly. Conservative surgery seems more cost effective than
      salpingectomy with additional IVF-ET.

PMID- 9236649
TI  - Medical abortion or vacuum aspiration? Two year follow up of a patient preference
      trial.
AB  - OBJECTIVE: To describe and compare health outcomes two years after medical
      abortion or vacuum aspiration in women recruited into a patient preference trial
      during 1990 to 1991. DESIGN: Women recruited to the original, partially
      randomised study were contacted for assessment using a structured interview.
      SETTING: Grampian region of Scotland, UK. PARTICIPANTS: One hundred and forty
      women who had participated in a partially randomised study of first trimester
      abortion two years previously. INTERVENTION: Vacuum aspiration or medical
      abortion using mifepristone and gemeprost. MAIN OUTCOME MEASURES: Long-term
      general, reproductive and psychological health; acceptability of procedure;
      perceived value of choice of method of termination. RESULTS: There were no
      significant differences between women who had undergone medical abortion or
      vacuum aspiration two years previously in general, reproductive or psychological
      health. Almost all women placed a high value on the provision of choice of method
      of termination. There was a significant difference in perception of long term
      procedure acceptability among women who had been randomised to a method of
      termination. CONCLUSIONS: Women should have the opportunity to choose the method
      of termination. This opportunity will result in high levels of acceptability,
      particularly at gestations under 50 days of amenorrhoea.

PMID- 9236651
TI  - Randomised trial of expectant versus surgical management of spontaneous
      miscarriage.
AB  - Thirty-five women with retained products of conception after spontaneous
      miscarriage were randomised to expectant (n = 19) or surgical (n = 16)
      management, respectively. Women were reviewed at one week, two weeks and six
      months. There were no significant differences in the number of days of pain,
      bleeding, sick leave or return to normal periods. Nine of twelve women from the
      expectant group and six of nine from the surgical group who attempted to conceive
      did so by six months. All 16 women were satisfied with conservative management.
      This study provides further reassurance when considering expectant management for
      spontaneous miscarriage both in the short and medium term.

PMID- 9236652
TI  - Randomised placebo controlled trial of mefenamic acid for premedication at
      outpatient hysteroscopy: a pilot study.
AB  - An increasing number of diagnostic hysteroscopies are being performed in an
      outpatient setting. Most women tolerate the examination well, but the single
      commonest reason for failure is pain. We assessed the efficacy of a nonsteroidal,
      anti-inflammatory analgesic as premedication before hysteroscopy in a double
      blind, placebo controlled trial. Our results showed that 500 mg mefenamic acid
      given one hour before hysteroscopy had no significant benefit in the discomfort
      experienced during the procedure but did significantly reduce pain after
      hysteroscopy. A larger dose or a longer interval between premedication and
      hysteroscopy may possibly be associated with greater benefits.

PMID- 9236653
TI  - The Kleihauer technique: an accurate method of quantifying fetomaternal
      haemorrhage?
AB  - Blood was taken from 100 consecutive asymptomatic women at 17 to 18 weeks of
      pregnancy for Kleihauer testing. When a proportion of these slides were assessed
      at a different hospital there was agreement in only 46%. When the number of fetal
      cells were quantified there were differences of over 500%. These results show a
      large inter-observer and inter-hospital variation in interpreting Kleihauer
      slides. If these investigations are to be performed, it is essential that
      clinicians can rely on the results. There is a need for quality control measures
      and audit so that laboratories can rectify any deficiencies in their techniques.

PMID- 9236654
TI  - The prevalence and consequences of missed abortion in twin pregnancies at 10 to
      14 weeks of gestation.
AB  - In singleton pregnancies at 10 to 14 weeks of gestation the prevalence of missed
      abortion is about 2%. In an ultrasound screening study at 10 to 14 weeks of
      gestation involving 492 twin pregnancies the prevalence of missed abortion was
      about twice as high as in singletons. The risk of subsequent miscarriage in twin
      pregnancies with one missed abortion was about ten times higher than in normal
      twin pregnancies. These findings may have important implications both in terms of
      counselling and for future research into the causes of miscarriage.

PMID- 9236655
TI  - Maternal serum alpha-fetoprotein in fetal neural tube and abdominal wall defects
      at 10 to 14 weeks of gestation.
AB  - Maternal serum alpha-fetoprotein concentration was determined in nine pregnancies
      with fetal anencephaly, seven with exomphalos containing liver, two with spina
      bifida and 100 normal controls at 10 to 14 weeks of gestation. The median alpha
      fetoprotein in the group with fetal anencephaly and exomphalos was significantly
      higher than in normal fetuses but the sensitivity of this test is likely to be
      only about 30% for a false positive rate of 5%.

PMID- 9236656
TI  - Dexamethasone-induced leucocytosis in pregnancy.
AB  - The effect of intramuscular dexamethasone administration in late pregnancy on the
      maternal peripheral white cell count was examined in 20 women. The mean total
      white cell count increased from a baseline of 11.3 x 10(9)/L (SD 2.3) to 16.2 x
      10(9)/L (SD 4.6) on day 1, normalising thereafter. This 43% increase represented
      composite changes in the neutrophil and lymphocyte counts which, on average,
      increased by 62% and decreased by 22%, respectively. It is concluded that
      prenatal dexamethasone induces a significant neutrophilia on the first day
      following administration. This information may be helpful when monitoring for
      infection.

PMID- 9236657
TI  - Acquired haemophilia, an unusual cause of severe postpartum haemorrhage.

PMID- 9236658
TI  - Posterior uterine rupture in a patient with a lower segment caesarean section
      scar complicating prostaglandin induction of labour.

PMID- 9236659
TI  - Treatment of large uterine fibroids.

PMID- 9236660
TI  - Treatment of large uterine fibroids.

PMID- 9236661
TI  - Recurrent stage IB cervical carcinoma: evaluation of the effectiveness of routine
      follow up surveillance.

PMID- 9236662
TI  - The management of cervical carcinoma within the south west region of England.

PMID- 9236663
TI  - The management of endometrial cancer.

PMID- 9236664
TI  - Preventing rhesus D haemolytic disease of the newborn by giving anti-D
      immunoglobulin: are the guidelines being adequately followed?

PMID- 9236665
TI  - Faecal incontinence after childbirth.

PMID- 9236666
TI  - The mythology of hormone replacement therapy.

PMID- 9236667
TI  - Impact of new methods on therapeutic abortion at the Royal Infirmary of
      Edinburgh.

PMID- 9236668
TI  - T cells in rheumatoid arthritis.

PMID- 9236669
TI  - Improving rheumatology with electronic communication.

PMID- 9236670
TI  - T-cell receptor in Sjogren's syndrome.
AB  - Studies on the TCR repertoire of T cells in several inflamed lesions of SS
      patients have shown that there exist no unique TCR V family genes, although TCR V
      gene usage is relatively restricted. Analysis of the clonality of infiltrating T
      cells shows that some T cells expand clonally in lesions, suggesting that these
      cells were induced by antigen-driven rather than superantigen-driven stimulation.
      The restricted usage of the TCRJ beta, V alpha and J alpha genes also supports
      the notion that all expanded T cells do not accumulate due to superantigen.
      Junctional sequence analysis has revealed some conserved amino acid sequence
      motifs in the TCR CDR3 region, which is the antigen-binding site on T cells.
      These observations strongly suggest that pathogenic T cells in lesions recognize
      limited epitopes on autoantigens in the context of HLA. These findings are
      similar to TCR on T cells in rheumatoid synovium, as described elsewhere [51].
      Intriguingly, T cells in lacrimal and labial salivary glands recognize common
      epitopes, but T cells in the kidney react with different autoantigens from those
      in minor salivary glands. In the future, the peptides recognized by pathogenic
      autoreactive T cells should be clarified to elucidate the mechanism for the
      progression of SS. Moreover, we predict that a vaccination with analogue
      peptides, to induce autoreactive T cells to anergy, might provide a new strategy
      for the specific treatment of SS.

PMID- 9236671
TI  - The relationship between HLA-DRB1 alleles and disease subsets of rheumatoid
      arthritis in Japanese.
AB  - To assess the association between HLA-DRB1 and the pathogenesis of rheumatoid
      arthritis (RA) in the Japanese population, we typed for HLA-DRB1 alleles in 852
      Japanese patients. An analysis of HLA-DRB1 allele associations was performed on
      the overall group and in three disease subsets of adult-onset RA, classified
      according to the extent of joint destruction evident on plain radiograms, i.e.
      least erosive subset (LES), more erosive subset (MES) and most erosive subset
      with mutilating disease (MUD). The Japanese RA patients with positively
      associated with DRB1*0101 and *0405, and negatively associated with DRB1*0701,
      *0802, *1302 and *1405. DRB1*0101 was associated more strongly with a milder
      disease subset and the relative risk (RR) was 1.9, 1.5 and 1.2 for LES, MES and
      MUD, respectively. On the other hand, DRB1*0405 was associated more strongly with
      a more severe disease subset, the RR being 1.8, 4.0 and 4.3 for LES, MES and MUD,
      respectively. These findings suggest that RA is a heterogeneous disease, not only
      clinically, but also in terms of its immunogenetic background, and that HLA-DRB1
      can be a useful prognostic factor for RA.

PMID- 9236672
TI  - Relationship between pentosidine levels in serum and urine and activity in
      rheumatoid arthritis.
AB  - Pentosidine is one of the advanced glycation end-products and is formed by
      glycosylation and oxidation. The aim of this study is to investigate the
      relationship between serum and urinary pentosidine levels and the activity of
      rheumatoid arthritis (RA). Using HPLC with column switching, we measured
      pentosidine in serum and urine from 77 patients with RA and 62 normal control
      subjects. The clinical features, blood biochemistry and activity of inflammation
      were examined in RA patients. Serum and urinary pentosidine in RA were
      significantly higher than in controls. Pentosidine significantly correlated with
      age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid
      factor, joint score and Lansbury Index in RA. The levels of pentosidine were
      higher in patients with active RA than in those with inactive RA. Serum and urine
      levels of pentosidine correlated with the activity of RA, and serum and urinary
      pentosidine may be a significant and novel marker for evaluating the disease
      status and the activity of RA.

PMID- 9236673
TI  - Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in
      rheumatoid arthritis patients following anti-tumour necrosis factor-alpha (cA2)
      therapy.
AB  - Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum samples
      from rheumatoid arthritis (RA) patients undergoing a double-blinded placebo
      controlled trial with the chimaeric anti-tumour necrosis factor (TNF)-alpha
      antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent MMP-3 (P < 0.001)
      levels were elevated in all RA patients prior to the commencement of the trial
      compared with normal control sera. Following cA2 therapy, MMP-1 and MMP-3 levels
      were assessed in the placebo, and 1 and 10 mg/kg cA2-treated groups at 7, 14, 21
      and 28 days. In both the 1 and the 10 mg/kg cA2-treated groups, a significant
      decrease in serum MMP-3 levels at all time points was observed, reducing
      maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced,
      but less dramatically than MMP-3, to 85% of pre-infusion values after 14 days in
      the 10 mg/kg cA2 treated group. In a separate non-placebo-controlled study, we
      also evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in
      plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the normal
      control range, but were significantly reduced (P < 0.035) 14 days after infusion
      to 72% of pre-infusion values. This study confirms previous reports that MMP-3
      levels are elevated and correlate with measures of inflammation in RA, and
      furthermore demonstrate that serum MMP-3 and MMP-1 levels are downmodulated
      following anti-TNF-alpha antibody therapy. Whilst serum MMP-3 levels correlated
      with C-reactive protein (CRP) both prior to and following anti-TNF-alpha antibody
      therapy, it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels
      reflect the cartilage and bone resorptive processes which are evident in this
      disease.

PMID- 9236674
TI  - Immunolocalization of inducible nitric oxide synthase in synovium and cartilage
      in rheumatoid arthritis and osteoarthritis.
AB  - Nitric oxide has been implicated as a mediator of inflammatory arthritis, and
      recent work has shown that pro-inflammatory cytokines stimulate NO production in
      vitro by activation of the inducible nitric oxide synthase (iNOS) pathway. In
      order to identify the cellular sources of NO production within the joint, we have
      used immunohistochemical techniques to study the distribution of iNOS in synovium
      and cartilage from normal and diseased joints. iNOS was most strongly expressed
      in the synovial lining layer, subsynovium, vascular smooth muscle and
      chondrocytes from patients with rheumatoid arthritis (RA). Analysis of serial
      sections, coupled with double immunofluorescent staining, showed that the CD68+
      macrophages in the synovial lining layer and, to a lesser extent, fibroblasts
      were the predominant source of iNOS within synovium, whereas T cells, B cells and
      neutrophils were negative. A similar pattern of iNOS staining was seen in
      osteoarthritis, but fewer cells were iNOS positive and the intensity of staining,
      particularly in cartilage, was much weaker than in RA. In contrast, no evidence
      of iNOS was detected in non-inflammatory synovium or in cartilage derived from
      normal joints (fractured neck of femur). In conclusion, these data support the
      hypothesis that synovium and cartilage are important sources of increased NO
      production in patients with inflammatory arthritis. Localization of iNOS at these
      sites within the inflamed joint raises the possibility that increased local
      production of NO may contribute to the pathogenesis of inflammatory arthritis by
      increasing synovial blood flow and by modulating cellular function within
      synovium and articular cartilage.

PMID- 9236675
TI  - Elevated serum levels of neopterin in adult patients with
      polymyositis/dermatomyositis.
AB  - We determined serum concentrations of neopterin, soluble tumour necrosis factor
      (55 kDa) receptor (sTNF-R) and soluble interleukin-2 receptor (sIL-2R) in plasma
      of 44 patients with polymyositis (PM)/dermatomyositis (DM), including 15 patients
      with primary PM, 13 patients with primary DM, and 16 patients with myositis and
      systemic sclerosis in overlap. Concentrations of neopterin, sTNF-R and sIL-2R
      were measured using commercially available immunoassays. Serum neopterin was
      increased in 35 of 44 PM/DM patients (80%), sTNF-R in 14 (32%) and sIL-2R in 18
      (41%) patients, respectively. There were significant correlations between serum
      neopterin and sTNF-R, sIL-2R and erythrocyte sedimentation rate (all P < 0.001).
      Neopterin, as well as sTNF-R and sIL-2R, did not correlate with clinical
      (neuromuscular and activities of daily living scores) and laboratory (creatine
      kinase levels) manifestations of myositis. Increased serum levels of neopterin
      were associated with non-muscular manifestations of PM/DM. In conclusion, serum
      neopterin appears to be a useful laboratory marker for ongoing immune activation
      and global disease activity in PM/DM.

PMID- 9236676
TI  - Mycoplasmal arthritis in patients with primary immunoglobulin deficiency:
      clinical features and outcome in 18 patients.
AB  - A survey of 358 patients with primary antibody deficiency shows that mycoplasmal
      infection is the commonest cause of severe chronic erosive arthritis. We review
      our experience with 18 patients with confirmed or probable mycoplasmal arthritis.
      There was a broad spectrum of severity from a monoarthritis rapidly responding to
      tetracyclines to severe debilitating polyarthritis, sometimes with antibiotic
      resistant organisms which in two cases were eliminated following hyperimmune
      animal serum therapy. Most patients had very low serum 1gG levels at the onset of
      arthritis, suggesting that maintaining levels within the normal range with
      immunoglobulin replacement may prevent infection. The unique susceptibility of
      these patients to mycoplasmal arthritis shows that antibodies play a crucial role
      in protection against these organisms.

PMID- 9236677
TI  - Autonomic dysfunction in systemic sclerosis: time and frequency domain 24 hour
      heart rate variability analysis.
AB  - To evaluate the autonomic nervous control of the heart in patients with systemic
      sclerosis (SSc), spontaneous heart rate variability was investigated by means of
      time-domain and spectrum analysis of 24 h ECG ambulatory recordings in 30 SSc
      patients (four males, aged 45.2 +/- 9 yr, mean +/- S.D., range 27-60) and 30 age
      matched healthy subjects. A significantly higher heart rate (P < 0.01) and lower
      circadian and spectral indices of heart rate variability (P < 0.01) were observed
      in SSc patients, compared with controls. A predictive value of age (P = 0.002),
      tachycardia (P = 0.002), circadian heart rate variability (P = 0.0025) and
      spectral power values (P = 0.005) for patient mortality was found. Moreover, the
      relative risk of death was higher (P = 0.05) in older subjects with circulating
      anti-Scl70. These abnormalities, detectable by a feasible, non-invasive
      diagnostic approach, indicate the presence of autonomic cardiac neuropathy in SSc
      patients.

PMID- 9236678
TI  - Lung findings on high-resolution computed tomography in idiopathic ankylosing
      spondylitis--correlation with clinical findings, pulmonary function testing and
      plain radiography.
AB  - Previous studies on the association of ankylosing spondylitis and abnormalities
      of the lung parenchyma have been based largely on plain radiography and pulmonary
      function testing. This study, although uncontrolled, is the first to use high
      resolution computed tomography to examine the entire lung parenchyma in
      ankylosing spondylitis patients, and to correlate the findings with clinical
      assessment, plain radiography and pulmonary function testing. The study
      population comprised 26 patients meeting the New York criteria for idiopathic
      ankylosing spondylitis who attended the out-patient department at our
      institution. High-resolution computed tomography examination revealed
      abnormalities in 19 patients (70%): these included interstitial lung disease (n =
      4), bronchiectasis (n = 6), emphysema (n = 4), apical fibrosis (n = 2), mycetoma
      (n = 1) and non-specific interstitial lung disease (n = 12). Plain radiography
      was abnormal in only four patients and failed to identify any patient with
      interstitial lung disease. All patients with interstitial lung disease on high
      resolution computed tomography had respiratory symptoms and three of the four had
      evidence of a restrictive process on pulmonary function testing. This study
      raises, for the first time, the possible association between interstitial lung
      disease and ankylosing spondylitis, and highlights the use of high-resolution
      computed tomography in detecting such disease in ankylosing spondylitis patients.

PMID- 9236679
TI  - Detection of joint pathology by magnetic resonance imaging in patients with early
      rheumatoid arthritis.
AB  - Magnetic resonance imaging (MRI) permits the visualization of anatomical
      structures not appreciated by conventional radiographic imaging, and may assess
      inflammatory disease and its progression with greater sensitivity than
      conventional radiography. In this study of 30 patients with early rheumatoid
      arthritis (RA), which could be considered as a pilot study because of the
      relatively small number of patients, we compare MRI of the knee and the fifth
      metatarsophalangeal joint with clinical and radiographic findings. A parallel
      study of 10 healthy individuals served as a reference group. In all but one of
      the 30 patients, MRI revealed some kind of joint abnormality, whereas
      conventional radiography was normal in 14 patients. The present study thus
      suggests that MRI may detect inflammatory and/or destructive joint changes in
      patients with early RA, and that these changes may occur in the absence of
      clinical symptoms or signs and/or radiographic signs in the examined joint. If
      these data prove to be confirmed in further controlled studies, MRI may be of
      importance both for the assessment of prognosis and for the decision to treat in
      the early critical stages of RA.

PMID- 9236680
TI  - Decreased survival in patients with co-existent rheumatoid arthritis and
      bronchiectasis.
AB  - The aim was to compare the 5 yr survival in patients with rheumatoid arthritis
      (RA) alone, bronchiectasis (Br) alone and RA plus Br (RA-Br). A case-control
      study was carried out in which 32 patients with RA-Br were matched for age
      (within 5 yr), sex and (where possible) disease duration with 32 patients with RA
      alone. An additional comparison group of 31 unselected patients with Br was
      chosen. All patients were followed for 5 yr. Patients with RA-Br were 7.3 times
      more likely to die than the general population, 5.0 times more likely than the RA
      group and 2.4 times more likely than the Br group. An increased risk of death
      within the RA-Br group was associated with a history of smoking, more severe RA
      and steroid usage. The co-existence of RA and Br is associated with a poor 5 yr
      survival.

PMID- 9236681
TI  - Pinioning the American rheumatologist.

PMID- 9236682
TI  - IgA nephropathy in a patient with Behcet's syndrome--case report and review of
      literature.
AB  - A 25-yr-old Turkish patient who presented with oral and genital ulcers, erythema
      nodosum and peripheral arthritis was diagnosed as having Behcet's syndrome (BS).
      The patient had normal renal function, but persistent proteinuria with 3 g
      protein loss/day. Renal biopsy revealed glomerulonephritis (GN) with IgA deposits
      in the membrane. Co-occurrence of BS and IgA nephropathy (IgAN) has only been
      reported once to date. In contrast to the statements in most current textbooks on
      BS, the review of the literature presented here suggests that renal involvement
      is not infrequent, but serious kidney disease is a rather rare event in Behcet's
      disease.

PMID- 9236683
TI  - Life-threatening transient neonatal Behcet's disease.
AB  - This case report describes transient neonatal Behcet's disease, with life
      threatening complications in the neonate. Male Baby R developed blood-streaked
      diarrhoea 5 days after birth, followed by recurrent severe scarring orogenital
      ulceration and vasculitic skin lesions. In this sixth week of life, he developed
      stridor leading to a respiratory arrest and necessitating assisted ventilation.
      No infective cause was isolated. Baby R responded well to i.v. and subsequent
      oral steroid therapy. At 8 weeks old he had fully recovered and remains well.
      Baby R's mother was not previously known to have Behcet's disease. During the
      pregnancy, she began to suffer orogenital ulceration, associated with skin
      lesions typical of Behcet's disease. Mild orogenital ulceration has become
      recurrent.

PMID- 9236684
TI  - Soft-tissue involvement in systemic lupus erythematosus.

PMID- 9236685
TI  - Imaging in transient regional osteoporosis.

PMID- 9236686
TI  - On surgical microarteriolysis for treatment of Raynaud's phenomenon in
      scleroderma.

PMID- 9236687
TI  - Erythema nodosum associated with Sjogren's syndrome.

PMID- 9236688
TI  - The value of temporal artery biopsy in suspected cranial arteritis.

PMID- 9236689
TI  - The value of arthrography in steroid injection of the shoulder joint.

PMID- 9236690
TI  - Antiperinuclear factor in early synovitis.

PMID- 9236691
TI  - Severe hypercalcaemia syndrome with daily low-dose vitamin D supplementation.

PMID- 9236692
TI  - What's the baby like?

PMID- 9236694
TI  - A hypothesis for the aetiology of spastic cerebral palsy--the vanishing twin.
AB  - The aetiology of spastic cerebral palsy (CP), in the majority of cases, is not
      known but the general consensus is that cerebral impairment occurs prepartum. In
      monochorionic twin pregnancies, death of one twin late in gestation is recognised
      as being an important risk factor for the surviving cotwin to have CP. It has
      been suggested that a significant proportion of singletons with spastic CP may be
      the result of death of a cotwin in the second half of gestation. In this paper it
      is hypothesised that spastic CP of unknown aetiology is the result of the death
      of a monochorionic cotwin and that the death of the cotwin may impair the
      neurological development of the survivor throughout gestation. If so, vanishing
      twin syndrome, which is now a recognised phenomenon revealed by ultrasound
      examination in early pregnancy, is important in the aetiology of spastic CP.

PMID- 9236693
TI  - The effect of intracranial pressure on myelination and the relationship with
      neurodevelopment in infantile hydrocephalus.
AB  - The effect of raised intracranial pressure (ICP), due to infantile hydrocephalus,
      on the process of myelination has been suggested in the literature. In this study
      19 hydrocephalic infants were followed-up with anterior fontanelle pressure (AFP)
      measurement (assessment of ICP), MRI (assessment of the myelination process and
      the CSF volume), and neurodevelopmental testing (NDT). There was a high
      correlation (r = 0.80) between the myelination and NDT scores. The size of the
      CSF volume showed a poor correlation with the mean AFP, the degree of myelination
      and the NDT scores. There was, however, a significant correlation between the
      mean AFP and the degree of myelination (r = 0.67) and also between the mean AFP
      and the NDT scores (r = 0.70). Longer-term follow-up (mean = 27 months) showed a
      significant correlation between the early progress of myelination and later
      developmental level (r = 0.78). Most of the children with a severely delayed
      myelination, preoperatively, showed a recovery of myelination following CSF
      drainage. It was concluded that: (1) raised ICP is related to developmental
      outcome, through the process of myelination; (2) the delay in myelination can be
      (partially) reversible; and (3) CSF volume is of minor importance regarding
      neurodevelopment.

PMID- 9236695
TI  - Longitudinal study of neuropsychological outcome in blind extremely-low
      birthweight children.
AB  - This study evaluated neurological and psychological development in 10 blind
      children over a 4-year period. Five of the children were born preterm with an
      extremely low birthweight (ELBW) and a diagnosis of retinopathy, whereas the
      other five were term. All children received their first neurological examination
      at a mean age of 10 months and then annual follow ups. In addition, the Bielefeld
      Developmental Test for Blind Infants and Preschoolers (BDTB) was administered
      every 6 months (from the ages of 18 to 48 months) to assess developmental outcome
      in different domains (e.g. cognition, language, gross motor abilities). Results
      showed a higher number of peri- and neonatal complications in blind ELBW children
      as well as a significantly higher number of neurological symptoms over the 4-year
      period. At the mean age of 4 years 10 months, blind ELBW children had a
      significantly lower body weight, body height, head circumference, and body-mass
      index compared with the term children. Findings on psychological development
      revealed that blind ELBW children also had significantly lower scores on all
      domains covered by the BDTB. Finally, the overall score on the BDTB correlated
      significantly with gestational age, birthweight, duration of mechanical
      respiration, and days spent in hospital after delivery.

PMID- 9236696
TI  - Grating acuity and visual-field development in children with intraventricular
      hemorrhage.
AB  - Visual development was studied in 171 preterm children who had intraventricular
      hemorrhage (IVH) and in 73 healthy preterm (HPT) children who did not develop
      IVH. Binocular grating acuity was assessed at age 1 month; monocular grating
      acuity and binocular visual-field extent were assessed at 4, 8, 12, 17, 24, 30,
      36, and 48 months; and monocular H, O, T, V letter recognition acuity was tested
      at 36 and 48 months. A significantly greater proportion of IVH subjects than HPT
      subjects had ocular abnormalities. IVH subjects had significantly poorer grating
      acuity than HPT subjects at 1, 4, 8, 36, and 48 months, poorer recognition acuity
      than HPT subjects at 36 and 48 months, and smaller average field extent than HPT
      subjects at 4, 12, and 17 months. Acuity deficits were not related to grade of
      IVH or to the presence of periventricular leukomalacia, but may have been
      associated with the presence of ocular abnormalities or cerebral palsy in some
      IVH subjects.

PMID- 9236697
TI  - Possible effects of tetrahydrobiopterin treatment in six children with autism-
      clinical and positron emission tomography data: a pilot study.
AB  - Six children, between 3 and 5 years of age, having infantile autism according to
      DSM-III-R, were treated for 3 months with 6R-L-erythro-5,6,7,8
      tetrahydrobiopterin (R-BH4), a cofactor for tyrosine hydroxylases in the
      biosynthetic pathway of catecholamines and serotonin. A criterion for inclusion
      in the study was a relatively low level of R-BH4 in the cerebrospinal fluid. For
      clinical evaluation, the Parental Satisfaction Survey (PASS) was used every
      fourth week and the Griffiths Developmental Scales were used before starting and
      3 months after completing the treatment. During the treatment period, all parents
      reported improvements in the child's social functioning-mainly eye contact and
      desire to interact-and in the number of words or sounds which the child used.
      Small positive changes were noted on the Griffiths Developmental Scales between
      the two testing occasions. R-BH4 levels in CSF increased significantly after
      treatment. The positron emission tomography (PET) study showed that the high
      value of dopamine D2 receptor binding in the caudate and putamen decreased by
      about 10% towards the normal level after treatment with R-BH4. The observations
      in this open study indicate that the drug might be useful for a subgroup of
      children with autism, but there is a need for a larger double-blind study with a
      longer treatment period.

PMID- 9236698
TI  - Long-term melatonin treatment in blind children and young adults with circadian
      sleep-wake disturbances.
AB  - Oral melatonin therapy was used to treat-severe circadian sleep-wake disturbances
      in eight children and young adults in an open study. All patients were
      functionally blind, six of them because of defects in the anterior visual
      pathway. All were mentally retarded. Baseline sleep diaries kept by the
      caregivers before treatment showed non-24-hour sleep-wake syndrome. Diurnal
      variations in serum and urinary melatonin were examined. Melatonin secretion peak
      time was delayed in seven patients. Body temperature variation was out of phase
      relative to sleep and melatonin in five patients, and thus they had signs of
      internal desynchronisation. Melatonin given in the evening dramatically improved
      the sleep-wake pattern in all patients. The effect was maintained during long
      term therapy for between 1 and 6 years in six patients. One patient fell back
      into the earlier sleep pattern after 6 to 8 months, and another had increasing
      sleep disturbance because of reflux oesophagitis, although the improvement
      regarding the circadian component remained. No side effects have been noted
      during the therapy. Oral melatonin is promising as an efficient and seemingly
      safe alternative for treatment of severe circadian sleep disturbances.

PMID- 9236699
TI  - The progression of untreated lumbar kyphosis and the compensatory thoracic
      lordosis in myelomeningocele.
AB  - Radiographs of 37 patients with untreated lumbar kyphosis without congenital
      vertebral anomalies associated with myelomeningocele were analyzed. With an
      average interval between radiographs of 6.2 years, the kyphosis was noted to
      increase at a mean rate of 4.3 degrees per year without correlation to its
      initial magnitude. The compensatory lordosis was more variable and progressed at
      a mean of 2.5 degrees per year. Children under the age of 2 years were more
      likely to increase the Cobb angle and the height of their kyphosis. There was an
      inverse relationship between the height of the kyphus and the lumbar spine height
      and the resultant growth of each. A modified kyphotic index less than 4
      correlated with an increase in the curve and height of the kyphosis and the
      subsequent desire for surgery. Wide variability in radiographic parameters make
      predictions for an individual patient difficult.

PMID- 9236700
TI  - Feeding ability in Rett syndrome.
AB  - Feeding abilities in 20 individuals with Rett syndrome aged 1 1/2 to 33 years
      were investigated by history and clinical assessment during a meal, followed by
      videofluoroscopy of feeding. All were shown to have reduced movements of the mid
      and posterior tongue, with premature spillover of food and liquid from the mouth
      into the pharynx. They also showed delayed pharyngeal swallow, but otherwise
      pharyngeal problems were minimal. These findings were noted to be similar to
      those in Parkinson's disease. Those individuals with the most general
      neurological impairment tended to have the worst feeding problems and were
      smaller and malnourished.

PMID- 9236701
TI  - Cerebral palsy--the transition from youth to adulthood.
AB  - Service provision for those with cerebral palsy (CP) becomes fragmented after
      adolescence. Young people with CP in two age groups, their carers and associates,
      were interviewed, and use of health and social services was investigated. Leisure
      activities were also compared with a matched control group of able-bodied young
      people. Use of health and social services decreased when the children with CP
      left school, thereby increasing the demands upon carers. Carers expressed
      anxieties about the provision of services, and frustration in obtaining
      information about help. Findings from the questionnaires showed the young people
      with CP in both age groups to be socially less active than the controls. Among
      the subjects, the older age group was socially less active than the younger age
      group. Communication is poor both between the agencies providing care and between
      the agencies and the young person or carer. There is a need to identify those
      with responsibility for coordinated-care planning for adolescents with CP.

PMID- 9236702
TI  - Memory in utero?

PMID- 9236704
TI  - Aortic arch angiography prior to carotid endarterectomy. Is its continued use
      justified?
AB  - Patients with significant stenosis at the carotid bifurcation are traditionally
      subjected to four vessel aortic arch angiography prior to consideration for
      carotid endarterectomy. The advent of the non-invasive vascular laboratory has
      necessitated a reappraisal of this approach. AIMS: 1. Determine the yield from
      aortic arch angiography and its influence on surgical management. 2. Evaluate the
      accuracy of clinical examination and the non-invasive vascular laboratory in the
      detection of aortic arch branch lesions. METHODS: One hundred and twenty-nine
      consecutive patients undergoing evaluation for carotid endarterectomy were
      prospectively enrolled into the study. The protocol entailed: 1. Clinical
      recording of upper limb pulses, blood pressure and supraclavicular bruits. 2.
      Duplex scan examination to evaluate proximal inflow into the carotid arteries. 3.
      Four vessel aortic arch angiography to detect aortic branch lesions. Data from
      the non-invasive tests were compared to angiography. Patients with aortic arch
      branch lesions were further evaluated to determine the proportion requiring
      additional surgery. RESULTS: Nineteen patients had angiographic evidence of
      aortic branch disease (14.7%); six involved the common carotid artery, three the
      innominate artery and 10 the subclavian artery. All of these lesions were
      detected by the combination of unequal blood pressure, pulse deficit, bruit or
      duplex scan. Seven patients underwent additional surgery (5.4%) which included
      carotid-subclavian bypass (five), aortoinnominate bypass (one) and innominate
      endarterectomy (one). CONCLUSION: In patients with significant stenosis at the
      carotid bifurcation undergoing evaluation for carotid endarterectomy, aortic arch
      angiography is unnecessary except in a small percentage of patients with abnormal
      clinical and non-invasive findings.

PMID- 9236703
TI  - Expansion rates of abdominal aortic aneurysm: current limitations in evaluation.
AB  - OBJECTIVES: Literature on the expansion rate of infrarenal aortic aneurysm is
      scant. This review was carried out to assess whether there is a normal rate of
      expansion for infrarenal aortic aneurysms. DESIGN AND METHODS: Review of
      literature relating to abdominal aortic aneurysm (AAA) measurement and expansion
      rates. Articles were identified from a search of the computerised Medline
      database from 1966 onwards. RESULTS: Nine studies produced expansion rates for
      3.0-5.0 cm AAA ranging from 0.17 to 0.57 cm per year. Evaluation of these studies
      showed that they are not wholly comparable in terms of source population, sample
      size, disease definition and period of assessment. CONCLUSIONS: It is not
      possible to discuss with confidence the "normal" expansion rate of infrarenal
      aortic aneurysms at any diameter. To elucidate fully the behaviour of AAA, a
      clear and universal definition of AAA is required in order that it may be used
      within a large, multicentered prospective cohort study.

PMID- 9236705
TI  - Risk factors for intestinal ischaemia after aortoiliac surgery: a combined cohort
      and case-control study of 2824 operations.
AB  - OBJECTIVE: To identify risk factors for intestinal ischaemia after aortoiliac
      surgery. MATERIALS AND METHODS: Among 2824 patients operated on during 1987-93
      and registered prospectively in the Swedish Vascular Registry, 62 cases of
      postoperative intestinal ischaemia were identified. They were compared with the
      remaining 2762 patients through the registry and with a random sample of 127
      controls through patient records. Multivariate analysis was performed. RESULTS:
      Patients in shock operated on for ruptured aneurysms were at greatest risk of
      developing postoperative intestinal ischaemia. Excluding patients in shock,
      operation for aneurysmal disease and for occlusive disease carried the same risk.
      Renal disease, emergency surgery, age, type of hospital, aortobifemoral graft,
      operating time, cross-clamping time and ligation of one or both internal iliac
      arteries were independent risk factors. CONCLUSIONS: Patient-related haemodynamic
      risk factors together with surgical skill and decision making defines the risk
      for this serious complication.

PMID- 9236706
TI  - Long-term in vivo alterations of polyester vascular grafts in humans.
AB  - OBJECTIVES: To examine the influence of in vivo hydrolysis on the physical
      properties of polyester grafts and their correlation to the period of
      implantation in the human body. MATERIALS AND METHODS: Sixty-five explanted
      vascular grafts were obtained after 0-23 years of implantation due to suture
      aneurysms (18), occlusion (12), graft infection (12), failure of graft material
      (7) and post-mortem (16). The surface was examined by scanning electron
      microscopy, the molecular integrity by infra-red spectroscopy and physical
      strength by probe puncture. RESULTS: Scission of macromolecular chains and loss
      of strength were shown. It was demonstrated that hydrolytic degradation of
      polyester takes place with increasing time of implantation in humans. Analysis by
      linear regression showed that polyester grafts lose 31.4% of their bursting
      strength in 10 years and 100% in 25-39 years after implantation. CONCLUSIONS:
      Regular follow-ups of patients with aged vascular grafts and the precise
      documentation of implanted materials are necessary to estimate graft degradation.

PMID- 9236707
TI  - Effect of balloon angioplasty in femoropopliteal arteries assessed by
      intravascular ultrasound.
AB  - OBJECTIVE: To study the effects of balloon angioplasty (PTA) of the
      femoropopliteal artery with intravascular ultrasound (IVUS). MATERIALS AND
      METHODS: Corresponding IVUS cross-sections (n = 1033) obtained before and after
      PTA from 115 procedures were analysed. Vascular damage including plaque rupture,
      dissection and media rupture was assessed. Free lumen area (FLA), media-bounded
      area (MBA) and plaque area (PLA) were measured. RESULTS: After PTA vascular
      damage was seen at the target site in 83 (72%) arteries: plaque rupture in 30
      (26%), dissection in 66 (57%) and media rupture in 20 (17%) arteries. The FLA
      increased from 5.4 +/- 3.4 mm2 to 14.1 +/- 5.0 mm2 (p < 0.001), MBA increased
      from 26.9 +/- 10.0 mm2 to 32.9 +/- 10.7 mm2 (p < 0.001) and PLA decreased from
      21.6 +/- 8.5 mm2 to 18.8 +/- 8.0 mm2 (p < 0.001). The increase in MBA accounted
      for 68% of lumen gain. The frequency of vascular damage and the relative
      contribution of MBA increase and PLA decrease to luminal gain were not different
      in procedures with balloon diameter < or = 5 mm and > or = 6 mm. CONCLUSIONS:
      Vascular damage is common following PTA. Lumen gain is mainly due to vessel
      expansion and, to a lesser extent, to a decrease in plaque area.

PMID- 9236708
TI  - Vein quality influences neointimal hyperplasia in an organ culture model of human
      saphenous vein.
AB  - OBJECTIVES: The severity of pre-existing pathological changes in human saphenous
      vein (HSV) correlates with the development of vein graft stenosis and graft
      patency. The aim of this study was to investigate the influence of pre-existing
      intimal hyperplasia on development of the neointima in vitro, using an organ
      culture model. MATERIALS AND METHODS: Segments of HSV were harvested during
      coronary artery bypass surgery. Histology was performed on part of the vein; the
      remainder was maintained in culture. Pre-existing intimal thickness (PIT) in HSV
      from day 0 and neointimal thickness (NIT) in cultured HSV were measured using
      computerised image analysis on histological sections. Day 0 and 14 veins were
      compared with respect to intimal hyperplasia. RESULTS: Twelve pairs of veins were
      examined. A mean tissue ATP of 297 nmoles/g wet weight for cultured. HSV
      confirmed cell viability. Mean PIT was 180 microns (CI: 86-274) and mean NIT was
      60 microns (CI: 48-72), with a significant correlation between them using the
      Spearman Rank test (Rs = 0.72; p = 0.008). CONCLUSIONS: Pre-existing vein quality
      as measured by PIT correlates with the development of neointimal hyperplasia in
      culture, adding further support to clinical evidence that poor vein quality
      predisposes to vein graft stenosis due to an inherent susceptibility to intimal
      hyperplasia.

PMID- 9236709
TI  - Prediction of outcome after femoropopliteal balloon angioplasty by intravascular
      ultrasound.
AB  - OBJECTIVE: To evaluate intravascular ultrasound (IVUS) as a control procedure
      after femoropopliteal percutaneous transluminal angioplasty (PTA), and compare it
      with arteriography. DESIGN: Descriptive study. MATERIAL: Arteriographic and
      intravascular ultrasound data obtained from 18 patients (20 limbs) undergoing PTA
      of the superficial femoral or popliteal artery. The degree of stenosis, the
      diameter and area of the lumen and the morphological changes in the plaque were
      related to the short-term patency of the intervention, as evaluated by duplex
      scan and ankle branchial index. RESULTS: Fifteen arteries remained patent. Two
      occlusions and two stenoses developed during the first 3 months after the
      intervention and one occlusion occurred after 1 year. The following IVUS
      parameters were related to a favourable patency: presence of calcification;
      dissection or plaque rupture and residual stenosis of less than 70%. The
      arteriographically determined diameter reduction did not show predictive value.
      CONCLUSION: This study shows that in contrast to arteriography, IVUS revealed
      parameters predictive for patency following PTA.

PMID- 9236710
TI  - Femorotibial reconstructions for chronic critical leg ischaemia: influence on
      outcome by diabetes, gender and age.
AB  - OBJECTIVES: To analyse the influence of risk factors on the outcome of
      femorotibial reconstructions for chronic critical leg ischaemia. DESIGN: A
      longitudinal observational study of patients undergoing femorotibial
      reconstruction. SETTING: A regional hospital and an academic referral centre.
      MATERIALS: One hundred and eighty-eight patients undergoing 209 reconstructions
      to the tibial vessels for chronic critical leg ischaemia, 149 of them with in
      situ vein grafts. CHIEF OUTCOME MEASURES: Graft patency, leg salvage and survival
      rates. MAIN RESULTS: Severity of preoperative ischaemia influenced the immediate
      outcome of reconstruction. Increasing age did not influence graft patency, leg
      salvage or survival rates. A combination of female sex and diabetes was
      associated with low graft patency and leg salvage (52% and 42% at 18 months).
      Diabetes was associated with a decreased survival. CONCLUSIONS: With proper
      patient selection, patency and leg salvage rates in older (> 80 years) patient
      groups with multiple risk factors justify an active reconstruction policy.

PMID- 9236711
TI  - Critical and subcritical ischaemia.
AB  - OBJECTIVES: To stratify leg ischaemia into high and low risk groups with respect
      to outcome. METHODS: An evaluation of 20 recent publications, reporting the
      results of 6118 patients with critical ischaemia. Low and high risk patient
      groups are identified by the definition of critical ischaemia. These groups are
      analysed with respect to outcome of the patient and limb. MAIN OUTCOME MEASURES:
      Major amputation and mortality. RESULTS: From these data subcritical (rest pain
      and/or ankle pressure > 40 mmHg, n = 4089) and critical (tissue loss and/or ankle
      pressure < 40 mmHg, n = 2029) risk group of patients was identified. The 1, 3 and
      5-year mortality is 26%, 44% and 56% with or without reconstruction. For patients
      in the low risk group, 27% did not lose their leg within the year if treated
      conservatively. For patients in the high risk group, amputation was required by
      95% if treated conservatively, compared to 25% if treated with arterial
      reconstruction. CONCLUSION: Reconstructive surgery should be viewed from the
      following, more realistic, perspective. For patients with rest pain (and/or ankle
      pressure > 40 mmHg), 100% cumulative patency is equivalent to 64% resolution of
      symptoms at 1 year, as the rest may have improved without treatment. For high
      risk patients (tissue loss and/or ankle pressure < 40 mmHg), 100% cumulative
      patency is equivalent to 93% limb salvage at 1 year. Future reports should
      identify these two groups separately, as the dominant difference between outcome
      studies is the proportion of subcritical patients in the study rather than better
      surgical or radiological techniques. This stratification also has an important
      bearing on pharmacotherapy trials.

PMID- 9236712
TI  - Vessel wall and flow characteristics after carotid endarterectomy: eversion
      endarterectomy compared with Dacron patch plasty.
AB  - OBJECTIVES: Experimental studies have demonstrated that decreases in vessel wall
      compliance and increases in turbulence may contribute to (re)stenosis. We studied
      vessel wall and flow characteristics after endarterectomy with Dacron patch
      plasty and after eversion endarterectomy, and compared those findings with the
      characteristics of non-stenotic, unoperated carotid arteries (controls). METHODS:
      Seventy-four patients who underwent 84 carotid endarterectomies were studied
      postoperatively by ultrasonography (2-24 months) Recorded variables included the
      diameter of the bulb, strain, elastic modulus (stiffness), and presence of
      turbulent flow. RESULTS: The vessel wall and flow characteristics of the two
      groups differed significantly. The diameter was higher and the strain lower in
      Dacron patch plasty than in controls; eversion endarterectomy did not differ from
      controls. The elastic modulus was higher (stiffer) in Dacron patch plasty than in
      eversion endarterectomy; neither Dacron patch plasty nor eversion endarterectomy
      differed significantly from controls. The stiffness index was not significantly
      different between the groups. Turbulence was present in Dacron patch plasty and
      eversion endarterectomy when compared with controls. CONCLUSION: In diameter,
      strain and stiffness, the operated carotid artery resembles the non-stenotic,
      unoperated artery more closely after eversion endarterectomy than after Dacron
      patch plasty.

PMID- 9236713
TI  - The use of intravascular ultrasound as control procedure for the deployment of
      endovascular stented grafts.
AB  - OBJECTIVE: To assess whether intravascular ultrasound (IVUS), used systematically
      in a series of patients with abdominal aortic aneurysms (AAA), is a feasible
      control procedure to ensure correct transfemoral placement of endovascular stent
      grafts (TPEG). DESIGN: Descriptive study. MATERIALS AND METHODS: Fourteen
      patients with infrarenal aortic aneurysms were treated by the placement of one
      tube graft, 10 aorto-uni-iliac and three aorto-bi-iliac grafts. Arteriography and
      IVUS were performed before, during and after deployment of the graft to ensure
      correct placement in relation to side branches, and proper adaptation of the
      stents to the aortic wall. Postoperative CT-scan and arteriography served as
      control procedures. RESULTS: IVUS identified both renal arteries before graft
      deployment in eight of 13 (62%) patients. In the remaining patients only one
      renal artery was visualised due to interference from guidewires or the introducer
      system. Imaging during stent deployment was abandoned after IVUS catheter damage
      in two of three cases. Postprocedural IVUS was able to evaluate the expansion of
      the stents and the adaptation to the aortic wall in all instances. In four (29%)
      cases a leak was identified. Additional intervention included deployment of a
      further stent (n = 2) or redilation (n = 2). Covering of the renal arteries could
      only be indirectly determined by IVUS. CONCLUSION: IVUS can provide important
      decisive information before and after stented graft deployment, with the
      limitations that guidewires, introducer system and stents may cause interference.
      Contemporary IVUS designs are unsuitable for monitoring stent deployment.

PMID- 9236714
TI  - Quality of life analysis in patients with lower limb ischaemia: suggestions for
      European standardisation.
AB  - INTRODUCTION AND OBJECTIVES: In this era of evidence-based medicine and limited
      resources we seem obliged, on clinical and economic grounds, to demonstrate that
      we improve not only patient survival but also the quality of patients' lives.
      This study aims to determine the impact of increasing lower limb ischaemia on
      quality of life (QOL) and which of three commonly used generic QOL instruments is
      the most valid, reliable, and responsive to change in patients with lower limb
      ischaemia. PATIENTS AND METHODS: Two hundred and thirty-five patients, 144 men
      and 91 women, median age 68 years (range 41-87 years) were graded according to
      ISCVS suggested reporting standards, i.e. 16 mild, 116 moderate and 25 severe
      claudicants; 33 patients had rest pain and 45 tissue loss. Patients completed
      Short Form 36 (SF36), EuroQol (EQ-5D) and Nottingham Health Profile (NHP)
      questionnaires at interview. Additional copies of questionnaires were posted to
      80 patients prior to attendance. Correlation between the two sets of responses
      reflects test-retest reliability. Correlation between domains measured by the
      three instruments reflects convergent and divergent validity. Kruskal Wallis
      ANOVA detected QOL changes across the whole group. Spearman Rank was used to
      analyse validity and reliability. Responsiveness was analysed using the Mann
      Whitney U-test. RESULTS: Increasing lower limb ischaemia confers significant (p <
      0.05) deterioration in: SF36 measured: physical functioning, physical role, pain,
      general health, vitality, social functioning and mental health. EQ-5D measured:
      mobility, self-care, usual activities, pain and anxiety/depression. NHP measured:
      energy, pain, emotional reaction, sleep, social isolation and physical mobility.
      All three instruments are significantly reliable (rs > 0.7). The validity of SF36
      and NHP (rs = 0.68-0.78) is superior to EQ-5D (rs = 0.37-0.7). SF36 & NHP are
      equally responsive to changes in physical activity and pain. SF36 and EQ-5D are
      most responsive to changes in social activity. SF36 is most responsive to changes
      in psychological status. CONCLUSIONS: QOL deteriorates markedly with increasing
      lower limb ischaemia. The SF36 would appear to be the most appropriate generic
      QOL analysis tool for these patients. We recommend its widespread adoption
      throughout Europe, thus providing a standardised tool for reporting generic QOL.

PMID- 9236715
TI  - Development of an in vitro model to study the response of saphenous vein
      endothelium to pulsatile arterial flow and circumferential deformation.
AB  - OBJECTIVES: To develop an in vitro model of human saphenous vein bypass to
      facilitate study of the early adaptive responses of venous endothelium to
      arterial flow conditions. DESIGN MATERIAL AND METHODS: Segments of human
      saphenous vein (with or without external polytetrafluoroethylene (PTFE) stents to
      limit circumferential and radial deformation) were mounted in a bypass circuit
      and subjected to pulsatile flow with oxygenated Krebs solution to simulate
      arterial or venous flow conditions for a period of 90 min. The viability of the
      vein was assessed by the tissue ATP concentration and vasomotor responses to
      phenylephrine, sodium nitroprusside and bradykinin (endothelium-dependent).
      Immunohistochemistry was used to assess both endothelial preservation (CD31) and
      the expression of proteins involved in leukocyte adhesion: E-selectin, P-selectin
      and ICAM-1. Freshly excised veins were used as controls. RESULTS: The
      concentration of ATP was 320 +/- 11 nmol/g in freshly excised vein (n = 8) and
      following exposure to the arterial flow circuit increased to 566 +/- 60 nmol/g (n
      = 8, paired t-test, p = 0.003) in unstented veins and to 421 +/- 49 nmol/g (n =
      8, paired t-test, p = 0.002) in externally stented veins (with PTFE). Both
      endothelium-dependent and sodium nitroprusside-induced vasodilatation responses
      were preserved after veins were exposed to the arterial flow circuit, but the
      sensitivity to phenylephrine was increased: EC50 decreasing from 9 microM, p =
      0.008. There was a 5-10% decrease in staining area for CD31 after veins, stented
      or unstented, were exposed to the arterial flow circuit. However, after exposure
      to the arterial flow circuit, the staining area ratio for ICAM-1/CD31, which
      remained unchanged in externally stented veins, increased two-fold in unstented
      veins, p > 0.01: there were no changes in the staining area ratio P-selectin/CD31
      and no staining for E-selectin was observed. CONCLUSION: Vasomotor responses and
      tissue ATP concentration indicate that the viability of saphenous vein can be
      maintained for up to 90 min in an ex vivo flow circuit and the CD31 staining
      indicated endothelial preservation. This opens up the possibility of
      investigating the early changes in saphenous vein endothelium following exposure
      to arterial pressure, as at bypass surgery. First results suggest that there is
      rapid upregulation of the leukocyte adhesion molecule ICAM-1, which can be
      prevented by limiting the circumferential deformation of the vein with an
      external PTFE stent.

PMID- 9236716
TI  - Cortical protection by localized striatal injection of IL-1ra following cerebral
      ischemia in the rat.
AB  - Interleukin-1 (IL-1) receptor antagonist (IL-1ra) markedly reduces infarct volume
      induced by middle cerebral artery occlusion (MCAO) in the rat, when injected
      either centrally (intracerebroventricularly) or peripherally. The site or sites
      of action of IL-1 in stroke pathology, however, are not known. The present study
      investigated the site(s) of action of IL-1/IL-1ra in ischemic brain damage by
      studying the effects of local injection of IL-1ra into the cortex or striatum
      following permanent MCAO in the rat. Cortical injection of IL-1ra (5 micrograms)
      did not affect infarct volume in the cortex or striatum measured 24 h after MCAO.
      In contrast, striatal injection of IL-1ra ipsilateral to the infarction caused a
      significant and highly reproducible reduction of cortical (37%, p < 0.001) and
      striatal damage (27%, p < 0.001, corrected for edema) compared with vehicle
      injected animals. Injection of IL-1ra (5 micrograms) into the striatum,
      contralateral to the infarction, resulted in a small (9%) but significant (p <
      0.001) reduction of ipsilateral cortical damage, with no effect on ipsilateral
      striatal damage. Injection of a higher dose of IL-1ra (7.5 micrograms) in the
      contralateral striatum caused a further inhibition of ipsilateral cortical damage
      (24%, p < 0.001) and a significant reduction of ipsilateral striatal damage (16%,
      p < 0.001). In separate groups of rats, it was established that core temperature
      (measured continuously in free-moving animals with remote radiotelemetry) was not
      affected by striatal or cortical injection of IL-1ra. These data show that
      injection of IL-1ra into the striatum but not the cortex reduces infarct volume
      in both the striatum and the cortex, independently of effects on core
      temperature. These results imply that blocking striatal IL-1 contributes to IL
      1ra-protective effects. We hypothesize that IL-1 may influence striatal distal
      cortical damage through either the release of specific substances or activation
      of polysynaptic pathways.

PMID- 9236717
TI  - Laminin peptide ameliorates brain injury by inhibiting leukocyte accumulation in
      a rat model of transient focal cerebral ischemia.
AB  - Postischemic cerebral inflammation has been reported to contribute to ischemic
      brain damage. During inflammation, constituents of the extracellular matrix such
      as fibronectin and laminin are recognized by certain integrins or proteoglycans
      and play an important role in the cell adhesion process. The purpose of this
      study was to evaluate the efficacy of peptides derived from laminin on leukocyte
      accumulation, infarct size, and neurological outcome in rats subjected to 1 h of
      cerebral ischemia and 48 h of reperfusion. Forty-four animals were included in
      this study: transient ischemia without treatment (Group I), treatment with TG-1
      peptide (Group II), GD-1 peptide (Group III), and GD-6 peptide (Group IV). Group
      II showed a significant reduction of the leukocyte accumulation (p < 0.001) and
      infarct size (p = 0.015) when compared with Group I. The neurological grade of
      Group II was also significantly better than in Group I at 48 h after reperfusion
      (p = 0.012). Based on these data, which are the first to explore the therapeutic
      potential of this peptide in cerebral ischemia, laminin peptide may offer a novel
      therapeutic approach to allaying injury in ischemic stroke.

PMID- 9236718
TI  - Rapid alteration of tau in oligodendrocytes after focal ischemic injury in the
      rat: involvement of free radicals.
AB  - Glial inclusions containing the microtubule-associated protein tau are present in
      a variety of chronic neurodegenerative conditions. We now report a rapid and time
      dependent increase of tau immunoreactivity within oligodendrocytes after focal
      cerebral ischemia in the rat. The number of tau positive oligodendrocytes in the
      ipsilateral subcortical white matter increased six- to eightfold by 40 minutes
      after permanent middle cerebral artery occlusion (MCAO). Tau was detected using
      antibodies that label both the N- and C-terminal of the protein, suggesting
      accumulation of full-length protein within these cells. Pretreatment with the
      spin trap agent alpha-phenyl-tert-butyl-nitrone (PBN)(100mg/kg) reduced the
      number of tau-positive oligodendrocytes by 55% in the subcortical white matter of
      the ischemic hemisphere compared with untreated animals at 40 minutes after MCAO.
      In contrast, pretreatment with glutamate receptor antagonists MK-801 (0.5 mg/kg)
      or 2,3-dihydroxy-6-nitro-7-sulpfamoyl-benzo(f)quinoxaline (NBQX) (2 x 30 mg/kg),
      failed to reduce the number of tau-positive oligodendrocytes after 40 minutes of
      ischemia. The results indicate that oligodendrocytes respond rapidly to an
      ischemic challenge and that free radical-mediated mechanisms are involved in the
      cascade leading to increased tau immunoreactivity.

PMID- 9236719
TI  - Neuronal thread protein gene modulation with cerebral infarction.
AB  - Neuronal thread proteins (NTP) are a family of phosphoproteins expressed during
      neuritic sprouting. The 15 to 18 kD NTP cluster is associated with development
      and neuronal differentiation, whereas the 21 kD and 39 to 42 kD species are
      overexpressed in Alzheimer's disease, correlating with neurodegenerative
      sprouting and synaptic disconnection. Empirical observations suggested that NTP
      might also be modulated with central nervous system injury and stroke. In this
      study of both human and experimental (rat) focal cerebral infarcts, in situ
      hybridization and immunocytochemical staining revealed NTP gene expression up
      regulated in perifocal neurons. These findings were confirmed by quantitative
      Northern and Western blot analyses. Moreover, Western blot analysis demonstrated
      selectively increased expression of the 15 to 18 kD NTP species during the acute,
      subacute, and healing phases of cerebral infarction in both humans and
      experimental animals, corresponding with the expected period of neuronal repair.
      These results suggest an additional role for the 15 to 18 kD NTP species in
      neuritic sprouting required for neuronal regeneration after injury in the mature
      central nervous system.

PMID- 9236720
TI  - Expression of zinc finger immediate early genes in rat brain after permanent
      middle cerebral artery occlusion.
AB  - The prolonged expression of the leucine zipper fos/jun immediate early genes
      (IEG) has been correlated with neuronal death after cerebral ischemia. In this
      study, the expression of six zinc finger IEG was examined using in situ
      hybridization in adult rats after middle cerebral artery occlusion (MCAO) with
      the suture model. NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3, and Nurr1 mRNA were all
      induced throughout the ipsilateral cortex at 1 hour to 12 hours after MCAO. The
      cortical induction for most of the genes was greatest in the anterior cingulate
      and the anterior cerebral artery (ACA) and middle cerebral artery (MCA)
      transition zone. All of the zinc finger IEG were induced at 1 hour in all regions
      of hippocampus. NGFI-A and NGFI-B were induced in ipsilateral thalamus. Within
      areas of infarction, the basal IEG mRNA expression, and expression of the
      housekeeping gene cyclophilin A mRNA, decreased below control levels by 12 hours
      after the ischemia. Immediate early gene expression outside areas of infarction
      returned to control levels in most brain regions by 24 hours except for egr-3,
      which continued to be induced in the MCA/ ACA transition zone for 24 hours, and
      NGFI-A, which continued to be expressed in specific regions of the thalamus for
      72 hours. The induction of these IEG in the cortex is likely caused by ischemia
      induced cortical spreading depression, with the hippocampal and thalamic IEG
      induction being caused by activation of efferent cortical pathways to these
      regions. The prominent induction of NGFI-B, NGFI-C, egr-2, and egr-3 in the
      anterior cingulate cortex, the ACA/MCA transition zone, and medial striatum could
      reflect the ischemic regions around MCA infarcts. The prolonged NGFI-A expression
      observed in thalamus in this study, and in CA1 of hippocampus after global
      ischemia in the gerbil in a previous study, suggests that the prolonged NGFI-A,
      expression could be the result of or the cause of the delayed cell death.
      Prolonged NGFI-A expression, like c-fos and c-jun, seems to provide a marker for
      slowly dying neurons.

PMID- 9236721
TI  - Hypoxia-ischemia, but not hypoxia alone, induces the expression of heme oxygenase
      1 (HSP32) in newborn rat brain.
AB  - Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to
      produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a
      variety of agents such as heat, heme, and hydrogen peroxide. Evidence suggests
      that the bile pigments serve as antioxidants in cells with compromised defense
      mechanisms. Because hypoxia-ischemia (HI) increases the level of oxygen free
      radicals, the induction of HO-1 expression in the brain during ischemia could
      modulate the response to oxidative stress. To study the possible involvement of
      HO-1 in neonatal hypoxia-induced ischemic tolerance, we examined the brains of
      newborn rat pups exposed to 8% O2 (for 2.5 to 3 hours), and the brain of
      chronically hypoxic rat pups with congenital cardiac defects (Wistar Kyoto; WKY/
      NCr). Heme oxygenase-1 immunostaining did not change after either acute or
      chronic hypoxia, suggesting that HO-1 is not a good candidate for explaining
      hypoxia preconditioning in newborn rat brain. To study the role of HO-1 in
      neonatal HI, 1-week-old rats were subjected to right carotid coagulation and
      exposure to 8% O2/92% N2 for 2.5 hours. Whereas HO enzymatic activity was
      unchanged in ipsilateral cortex and subcortical regions compared with the
      contralateral hemisphere or control brains, immunocytochemistry and Western blot
      analysis showed increased HO-1 staining in ipsilateral cortex, hippocampus, and
      striatum at 12 to 24 hours up to 7 days after HI. Double fluorescence
      immunostaining showed that HO-1 was expressed mostly in ED-1 positive
      macrophages. Because activated brain macrophages have been associated with the
      release of several cytotoxic molecules, the presence of HO-1 positive brain
      macrophages may determine the tissue vulnerability after HI injury.

PMID- 9236722
TI  - Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of
      serotonin synthesis rate in vivo.
AB  - We describe the tracer kinetic analysis of [C-11]-labeled alpha-methyl-tryptophan
      (AMT), an analogue of tryptophan, which has been developed as a tracer for
      serotonin synthesis using positron emission tomography (PET) in human brain.
      Dynamic PET data were acquired from young healthy volunteers (n = 10) as a series
      of 22 scans covering a total of 60 minutes and analyzed by means of a three
      compartment, four-parameter model. In addition, functional images of the K
      complex were created using the Patlak-plot approach. The application of a three
      compartment model resulted in low identifiability of individual k-values,
      especially that of k3. Model identifiability analysis using a singular value
      decomposition of the final sensitivity matrix showed parameter identifiability to
      increase by 50% when the Patlak-plot approach was used. K-complex values derived
      by the Patlak-plot approach overestimated the compartmental values by 10 to 20%,
      because of the violation of the dynamic equilibrium assumption. However, this
      bias was fairly constant in all structures of the brain. The rank order of K
      complex values from different brain regions corresponded well to the regional
      concentrations of serotonin in human brain (P < 0.0001). These results indicate
      that the Patlak-plot method can be readily applied to [C-11]AMT data in order to
      create functional images of the K-complex, reflecting serotonin synthesis rate,
      within an acceptable error margin.

PMID- 9236723
TI  - Frequency-dependent changes of regional cerebral blood flow during finger
      movements: functional MRI compared to PET.
AB  - To evaluate the effect of the repetition rate of a simple movement on the
      magnitude of neuronal recruitment in the primary sensorimotor cortex, we used a
      blood flow-sensitive, echo planar functional magnetic resonance imaging (fMRI)
      sequence in six normal volunteers. Three of the volunteers also had [15O]water
      positron emission tomography (PET) studies using the same paradigm. Previous PET
      studies had shown an increase in regional CBF (rCBF) with movement frequencies up
      to 2 Hz and then a plateau of regional cerebral blood flow (rCBF) at faster
      frequencies. To evaluate the extent of the activation, the correlation
      coefficient (cc) of the Fourier-transformed time-signal intensity change with the
      Fourier-transformed reference function was calculated pixel by pixel. The degree
      of activation was measured as the signal percent change of each region of
      interest with a cc > 0.5. The left primary sensorimotor cortex was constantly
      activated at 1, 1.5, 2, and 4 Hz, while there was only inconsistent activation at
      0.25 and 0.5 Hz. Percent change in signal intensity linearly increased from 1 to
      4 Hz. Area of activation increased up to 2 Hz and showed a tendency to decrease
      at higher frequencies. Individual analysis of PET data showed activation in the
      same location as that revealed by fMRI. The combination of progressively
      increasing signal intensity with an area that increases to 2 Hz and declines at
      faster frequencies explains the PET finding of plateau of rCBF at the faster
      frequencies. Functional magnetic resonance imaging shows similar results to PET,
      but is better able to dissociate area and magnitude of change.

PMID- 9236724
TI  - Effect of aging on regulation of brain stem circulation during hypotension.
AB  - This study was designed to determine age related changes in autoregulatory
      responses of the brain stem circulation in vivo. In anesthetized adult (4 to 6
      months, n = 8) and aged (24 to 26 months, n = 7) Sprague-Dawley rats, local CBF
      to the brain stem was determined with laser-Doppler flowmetry and diameters of
      the basilar artery and its branches were measured through an open cranial window
      during stepwise hemorrhagic hypotension. In aged rats, the lower limit of CBF
      autoregulation shifted upward to 60 to 75 mm Hg from 30 to 45 mm Hg in adult
      rats. Dilator responses of the basilar artery (baseline diameter: 254 +/- 15
      microns), large branch (109 +/- 23 microns), and small branch (44 +/- 10 microns)
      to hypotension were much smaller in aged rats than in adult rats. The maximum
      change in diameter of the basilar artery during profound hypotension was
      significantly smaller in aged rats (11 +/- 8%) than that in adult ones (23 +/-
      12%, P < 0.05); that of the large branch was 12 +/- 8% versus 33 +/- 17% (P <
      0.005); and that of the small branch was 17 +/- 7% versus 40 +/- 13% (P <
      0.0005), suggesting greater attenuation of the responses in the smaller vessels.
      Thus, this study provides direct evidence that aging diminishes the compensatory
      dilatation of brain stem arterioles and arteries during hypotension and modifies
      the autoregulatory plateau of CBF, which seems to increase the risk of the brain
      stem ischemia during hypotensive conditions.

PMID- 9236725
TI  - Autoradiographic evidence for flow-metabolism uncoupling during stimulation of
      the nucleus basalis of Meynert in the conscious rat.
AB  - We earlier reported that electrical stimulation of the rat nucleus basalis of
      Meynert (NBM) induces large cerebral blood flow increases, particularly in
      frontal cortical areas but also in some subcortical regions. The present study
      was designed to address the issue of blood flow control exerted by NBM
      projections. To this aim, we have determined whether these flow increases were
      associated with proportionate changes in metabolic activity as evaluated by
      cerebral glucose utilization (CGU) strictly under the same experimental
      conditions in the conscious rat. An electrode was chronically implanted in a
      reactive site of the NBM as determined by laser-Doppler flowmetry (LDF) of the
      cortical circulation. One to two weeks later, while the cortical blood flow was
      monitored by LDF, we measured CGU using the [14C]2-deoxyglucose autoradiographic
      technique during unilateral electrical stimulation of the NBM, and analyzed the
      local flow-metabolism relationship. The large increases in cortical blood flow
      induced by NBM stimulation, exceeding 300% in various frontal areas, were
      associated with at most 24% increases in CGU (as compared with the control group)
      in one frontal area. By contrast, strong increases in CGU exceeding 150% were
      observed in subcortical regions ipsilateral to the stimulation, especially in
      extrapyramidal structures, associated with proportionate CBF changes. Thus, none
      of the blood flow changes observed in the cortex can be ascribed to an increased
      metabolic activity, whereas CBF and CGU were coupled in many subcortical areas.
      This result indicates that different mechanisms, which do not necessarily involve
      any metabolic factor, contribute to the regulation of the cerebral circulation at
      the cortical and subcortical level. Because the distribution of the uncoupling is
      coincident with that of cholinergic NBM projections directly reaching cortical
      microvessels, these data strongly support the hypothesis that NBM neurons are
      capable of exerting a neurogenic control of the cortical microcirculation.

PMID- 9236727
TI  - Cerebral glucose utilization is reduced in second test session.
AB  - Cerebral glucose utilization was higher during the first positron emission
      tomography (PET) session than during the second session, as assayed using the PET
      [18F]fluorodeoxyglucose method in male human volunteers. This difference was due
      largely to data from subjects with low-trait anxiety, since subjects with high
      anxiety showed similar metabolism in both PET sessions. High-anxiety subjects
      showed greater right/ left ratios of cerebral metabolism than low-anxiety
      subjects, particularly during the second PET session. These findings suggest that
      the level of anxiety may be an important variable to consider in PET studies
      using multiple sessions.

PMID- 9236726
TI  - Measurement of cerebral blood flow in dogs with near infrared spectroscopy in the
      reflectance mode is invalid.
AB  - Near infrared spectroscopy (NIRS) is used to measure CBF (CBFNIRS) in humans,
      based on Fick's principle, using oxygen as an intravascular tracer. We compared
      CBFNIRS with CBF measured by microspheres (CBF mu) and the venous outflow
      technique (CBFv) in 15 dogs, altering CBF with ventilation-induced changes in
      PaCO2. Five hundred forty-nine CBFNIRS measurements were attempted using an
      integration time of 2.5 s on the saturation signal from the tongue. One hundred
      ninety-eight (36.1%) of the measurements fulfilled predefined criteria. The
      coefficient of variation (CV) for six measurements under stable conditions was
      29.1%. The CBFNIRS measurements correlated best with microsphere-measured blood
      flows in the cortical gray matter (median 0.43, range 0.16-0.93); the
      contributions of the skull and dura were variable. The CBFv varied by a median of
      12% (range 0-67%) during the CBFNIRS measurements. The percentage of acceptable
      CBFNIRS measurements, the CV, and the correlation coefficients of the CBFNIRS
      were improved by using saturation signal directly from the artery and varying the
      integration time with an estimate of the minimum transit time. The current method
      of measuring CBFNIRS in the reflectance mode is in-accurate when compared with
      other accepted techniques.

PMID- 9236728
TI  - Depression and anxiety: implications for nosology, course, and treatment.
AB  - International epidemiologic and clinical studies have shown that comorbid
      depression and anxiety is of major importance, resulting in more severe symptoms,
      impairment, subjective distress, and longitudinal course than either anxiety or
      depression alone. Threshold and subthreshold levels of anxiety ("A," "a") and
      depression ("D," "d") can be defined on the basis of duration, frequency,
      impairment, and number of symptoms. These letters can then be used to designate
      the various combinations of depression and anxiety, e.g., AD, aD. Current
      evidence demonstrates the importance of evaluating both threshold and
      subthreshold levels of depression and anxiety.

PMID- 9236729
TI  - Subthreshold syndromes of depression and anxiety in the community.
AB  - Nearly 50% of individuals in the community meet threshold or subthreshold
      diagnostic criteria for depression or anxiety, with depression being far more
      common. Co-occurrence of anxiety and depression is common, as the majority of
      individuals who experience anxiety also manifest threshold- or subthreshold-level
      depression. In the current study, addition of subthreshold categories improved
      the coverage of treated cases in the community by nearly a third; 61% of subjects
      were diagnosed according to threshold criteria while 89% were diagnosed according
      to subthreshold categories. These results suggest that inclusion of subthreshold
      level syndromes enhances the validity of diagnostic systems by increasing the
      proportion of treated cases that meet diagnostic criteria and by providing a more
      accurate representation of milder syndromes of depression and anxiety.

PMID- 9236730
TI  - Management of patients with depression associated with anxiety symptoms.
AB  - Current diagnostic classifications separate depression from anxiety, yet these
      conditions commonly coexist in clinical practice, forming a spectrum of disorders
      between these extremes. Treatment options for depression with anxiety include
      tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors
      (SSRIs). As SSRIs are nonsedating, this proves that sedation as produced by TCAs
      is not required for anxiolytic actions. SSRIs are effective in anxiety disorders
      and against anxiety symptoms in depressed patients. The adverse event profile of
      SSRIs compares favorably with that of TCAs, and SSRIs are much safer in overdose.
      When the diagnosis of depression with anxiety is established, it is important to
      institute prompt, effective treatment in view of the potential risk of suicide.
      The SSRIs appear to be the treatment of choice for such patients.

PMID- 9236731
TI  - Psychopharmacology of comorbid obsessive-compulsive disorder and depression.
AB  - A high degree of comorbidity appears to exist between obsessive-compulsive
      disorder (OCD) and depression, both with respect to symptomatology and at the
      syndromal level. It has been argued that nonspecific effects on dysphoric mood,
      anxiety, and depressive symptoms account for the therapeutic efficacy of
      antidepressants in OCD. However, several controlled studies have shown that
      neither the presence nor initial severity of depression has any impact on
      therapeutic improvement in OCD. In particular, studies with the serotonin
      selective reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine have revealed
      beneficial effects in OCD, irrespective of the presence of depressive symptoms.
      The efficacy of the other SSRIs in OCD requires further study. In conclusion, the
      improvement in OC symptoms seen with fluvoxamine and fluoxetine does not depend
      on concomitant affective disorder.

PMID- 9236732
TI  - Mixed depression and anxiety: serotonin1A receptors as a common pharmacologic
      link.
AB  - Although depressive and anxious symptoms frequently coexist, most studies tend to
      dichotomize anxiety disorders from depression. Consequently, pharmacologic agents
      are designated as antidepressants or anxiolytics. A number of developments are
      reversing this trend. One is changes in conceptualization of generalized anxiety
      disorder (GAD) and major depressive disorder to recognize the frequent existence
      of simultaneous symptoms of anxiety and depression in patients with related
      affective and anxiety disorders. A second is the increasing recognition that
      subsyndromal symptoms of anxiety and depression frequently exist that do not
      reach thresholds for GAD or depression but that may decompensate to overt anxiety
      disorder or depression. A third is the discovery of partial agonists for
      serotonin1A receptor subtypes that have promising efficacy in mixed depression
      and anxiety.

PMID- 9236733
TI  - Mixed anxiety and depression: from theory to practice.
AB  - The 10th International Classification of Disease (ICD-10) introduced the concept
      of mixed anxiety-depression to define patients presenting both anxiety and
      depressive symptoms of limited number and/or intensity, not sufficiently severe
      to fulfill criteria for a specific diagnosis of depressive or anxiety disorder.
      Epidemiologic surveys have shown that these patients may display significant
      levels of functional impairment, have unexplained somatic symptoms and a high use
      of nonpsychiatric medical care, have long-lasting symptoms, and are at risk for
      more severe psychiatric disorders. A DSM-IV field trial concluded that patients
      with affective-symptoms not meeting thresholds for DSM-III-R disorders were at
      least as common as patients with anxiety or mood disorders, and that their
      symptoms were associated with significant distress or impairment. Although some
      of these patients present residual symptoms from previous psychiatric episodes
      and may request treatment specific to these conditions, it is not known if those
      without a psychiatric history could benefit from pharmacologic or psychological
      treatments usually used in mild outpatient cases.

PMID- 9236734
TI  - The detection and consequences of anxiety in clinical depression.
AB  - Anxiety symptoms and comorbid anxiety are common in depressive syndromes, and
      there is evidence they are associated with increased severity of depression and a
      poorer outcome. Anxiety and agitation symptoms also appear to be an acute risk
      factor for suicide in patients who have major affective disorder, an observation
      that has been supported by a number of biological correlates. Rapid and
      aggressive treatment of these anxiety/agitation symptoms with suitable
      antidepressants or benzodiazepines should be considered in order to avoid the
      immediate risk of suicide and to permit successful treatment of the affective
      disorder.

PMID- 9236735
TI  - Antituberculosis drug resistance: practical solutions to practical problems.

PMID- 9236736
TI  - Infection and coronary heart disease.
AB  - A large body of evidence exists that implicates a number of microbial agents in
      the pathogenesis of coronary heart disease (CHD). This, if proven, may have far
      reaching implications for the prevention and treatment of CHD and other
      atherosclerotic disease. The histopathology of atherosclerosis and its natural
      history suggest infectious causation at many points along the progression of
      disease, particularly with regard to CHD, and a number of pathogens have been the
      focus of study. Viral agents implicated include Coxsackie B4 virus, for which
      tenuous sero-epidemiological associations exist, and the Herpesviridae. The
      animal herpesvirus causing Marek's disease in chickens causes atherosclerotic
      lesions in these animals. Herpes simplex virus I and II have been found in aortic
      smooth muscle and produce changes in vitro in smooth muscle that are similar to
      those seen at the beginning of atherosclerosis and which may also explain some of
      the features of atherosclerotic complications. Cytomegalovirus is implicated more
      strongly sero-epidemiologically by in-vivo detection in atherosclerotic lesions
      and by its links with post-cardiac transplant vasculopathya syndrome similar to
      atherosclerosis. Bacteria have also been shown to have links with CHD. Chlamydia
      pneumoniae and Helicobacter pylori have both been associated sero
      epidemiologically with CHD, and these findings have been consolidated by recent
      work showing their presence in atherosclerotic lesions in adults. Bacterial
      infections in general lead to many changes in lipid, thrombic and other acute
      phase protein metabolism, and some of these changes occur with both C. pneumoniae
      and H. pylori infections. The ubiquity and similar epidemiological features to
      CHD of all these microbial pathogens make the resolution of the causative issue
      impossible by retrospective means. All that can be shown at present are a variety
      of weak and strong links, the significance of which can only be determined by
      large and perhaps lifetime prospective studies.

PMID- 9236737
TI  - Identification of heparan sulphate binding surface proteins of Helicobacter
      pylori: inhibition of heparan sulphate binding with sulphated carbohydrate
      polymers.
AB  - Heparan sulphate binding to cells of the gastric pathogen Helicobacter pylori at
      pH 4-6 is common. Binding was inhibited by various unlabelled sulphated
      polysaccharides and at high ionic strength and pH, but not by carboxylated or non
      sulphated compounds. The inhibition by various sulphated compounds such as
      dextran sulphate and carrageenans was related to the sulphate content and not to
      the carbohydrate polymer backbone. The IC50 values for heparin and dextran
      sulphate for H. pylori strain 25 were calculated as 3.55 x 10(-7) M and 5.01 x
      10(-6) M respectively. Heparin-binding proteins of H. pylori are exposed on the
      cell surface, as shown by biotinylation of cell-surface proteins before
      separation of outer membranes and by an indirect immunofluorescence assay. The
      strongest biotin-heparin binding by H. pylori was observed with a polypeptide in
      the 55-60 kDa region.

PMID- 9236738
TI  - Formation of a dipeptidyl arylamidase by Bacteroides splanchnicus NCTC 10825 with
      specificities towards glycylprolyl-x and valylalanine-x substrates.
AB  - Bacteroides splanchnicus in common with several members of the B. fragilis group
      constitutively produced a number of protein and peptide hydrolysing enzymes.
      Amongst the most active was an arylamidase, which specifically hydrolysed the
      dipeptidyl chromogenic substrates glycylprolyl p-nitroanilide (GPRPNA),
      glycylprolyl beta-naphthylamide (GP beta NA) and valylalanine p-nitroanilide
      (VAPNA), and had some proteolytic activity towards azocasein. No activity was
      detected against proline beta-naphthylamide, glycine, valanine or alanine p
      nitroanilides. Physiological studies showed that the enzyme was largely cell
      associated during exponential growth in batch culture, but was progressively
      released by the bacteria before the cells entered stationary phase. Glycylprolyl
      arylamidase (GPA) was completely cell-bound during growth in continuous culture,
      where synthesis increased concomitantly with dilution rate (specific growth rate)
      in both carbon- and nitrogen-limited chemostats. Gel-filtration chromatography of
      B. splanchnicus cell extracts yielded a single peak of GPA activity, with an
      apparent molecular mass of c. 160 kDa, while one peak of enzyme activity was
      eluted by 0.3 M NaCl during cation-exchange chromatography. Activity staining of
      SDS polyacrylamide gels showed a single GPA band at 80 kDa, suggesting that the
      enzyme was a dimer. Two fractions of GPA activity were recorded during
      preparative isoelectric focusing with apparent isoelectric points of pH 3.51
      (fraction 3) and 3.95 (fraction 6), indicating the possible existence of GPA
      isoenzymes. GPRPNA, VAPNA and azocasein were hydrolysed by the major fraction
      (fraction 3), while only the p-nitroanilide substrates were hydrolysed by
      fraction 6. Studies with the partially purified enzyme obtained from gel
      filtration columns showed a relatively broad pH optimum at 7.5-8.2. Inhibition
      experiments demonstrated that while aspartic (pepstatin A), thiol (iodoacetate)
      and metalloprotease (EDTA, cysteine) inhibitors had little effect on hydrolysis
      of glycylproline p-nitroanilide, GPA was strongly inhibited (c. 80%) by 5 mM
      phenylmethylsulphonyl fluoride (PMSF), indicating it to be a serine enzyme.

PMID- 9236739
TI  - Toxin production by Burkholderia pseudomallei strains and correlation with
      severity of melioidosis.
AB  - An exotoxin lethal to cells in culture (cytolethal toxin, CLT) was identified in
      culture filtrates of Burkholderia pseudomallei, the causative organism of
      melioidosis. CLT could pass through a 10-kDa cut-off ultrafilter and its
      properties suggest that it is a peptide. Isolates from soil, animals and man
      showed differential cytolethality in vitro. The isolates were divided into low,
      medium and high CLT producers with soil isolates being low producers and isolates
      from patients with melioidosis encephalitis being high producers. CLT levels are
      subject to regulation, as a strain isolated from an infected goat was one of the
      highest producers whereas the same strain isolated from soil was a low producer.
      In addition to CLT, all isolates produced a protein with cell-elongating activity
      which was also present in culture filtrates.

PMID- 9236740
TI  - Ribotype differences between clinical and environmental isolates of Burkholderia
      pseudomallei.
AB  - Burkholderia pseudomallei is isolated frequently from the soil in regions where
      the disease melioidosis occurs. However, recent surveys in Thailand have shown
      that the frequency of isolation of the organism from soil samples is not directly
      related to the incidence of melioidosis in an area. To determine whether strain
      populations of B. pseudomallei prevalent in soil are gentypically related to
      strains causing clinical disease, rRNA BamHI restriction fragment length
      polymorphisms (RFLP) of 139 soil environmental isolates and 228 human isolates
      were compared. Two groups of ribotype patterns were found. Group I comprised 37
      different ribotype patterns which were characterised by five to eight
      hybridisation bands of 2.8- > 23 kb. All of these ribotypes were identified among
      the clinical isolates, and 18 of them were also found in 59 environmental
      isolates. Group II was represented by 12 ribotypes found only in environmental
      strains. These ribotype patterns comprised one to five bands in the size range 9-
      > 23 kb. All but one of the 73 isolates in this group grew on a minimal medium
      supplemented with L-arabinose. In contrast, only 3% of the 66 isolates from the
      environment with group I ribotype patterns could utilise this sugar as their sole
      energy source. These findings suggest that B. pseudomallei strains that utilise
      arabinose constitute a population that is genetically distinct from other
      environmental and clinical strains.

PMID- 9236741
TI  - Selective translocation of coliform bacteria adhering to caecal epithelium of
      rats during catabolic stress.
AB  - Adult conventional rats were starved for 48 h with or without haemorrhage at 24
      h, and translocation of caecal coliforms to mesenteric lymph nodes (MLNs) was
      measured. Translocation was detected in three of 11 rats without haemorrhage, in
      6 of 11 starved and sham-operated rats and in 12 of 22 rats after haemorrhage. In
      contrast, only one of 13 non-instrumented and fed control rats showed
      translocation. Translocation was associated with more coliforms adhering to
      caecal epithelium in rats. Coliform isolates from caecum, caecal epithelium and
      MLNs were characterised and grouped into different biochemical phenotypes (BPTs)
      by a biochemical fingerprinting method. Of 291 BPTs detected in the caecum of all
      rats, 108 were also found on caecal epithelium; 36 BPTs were detected in MLNs, of
      which 17 were not detected either in the caecum or on the caecal epithelium of
      the corresponding rats. One isolate from each of these 36 BPTs was selected and
      compared to the others. Four common (C) BPTs (i.e., C1-C4) were identified among
      them. Strains of C1 formed the majority of isolates from the caecum (79%), caecal
      epithelium (71%) and MLNs (91%). In contrast, C2-C4 had a significantly lower
      incidence both in the caecum and on the caecal epithelium, but not in the MLNs.
      These findings indicate that not all caecal coliforms adhere to the epithelium
      during catabolic stress and that for translocation to occur, other bacterial
      properties besides adhesion are needed. It is also concluded that coliforms with
      a low incidence in the caecum can translocate with the same efficiency as those
      with a high incidence.

PMID- 9236742
TI  - Growth and cultural characteristics of Calymmatobacterium granulomatis--the
      aetiological agent of granuloma inguinale (Donovanosis).
AB  - Granuloma inguinale is a chronic destructive granulomatous disease of the
      genitalia. The clinical diagnosis is often unreliable and the definitive
      diagnosis is based on the visualisation of 'Donovan bodies' in tissue smears or
      biopsy specimens. The organism implicated in its aetiology, Calymmatobacterium
      granulomatis, was reported to have been cultured > 30 years ago, but little is
      known about the organism because of its fastidious nature and the difficulty in
      culturing it. Twenty-two biopsy specimens from female patients with clinical and
      laboratory-confirmed granuloma inguinale were treated with amikacin 10 mg/L and
      inoculated in a monocyte co-culture system with peripheral blood mononuclear
      cells (PBMC) from a single donor and autologous sera. The method was subsequently
      modified by pretreatment of specimens with vancomycin 5 mg/L and metronidazole 10
      mg/L in addition to amikacin 10 mg/L for the purpose of decontamination, pooled
      blood donor PBMC and by the use of heat-inactivated fetal calf serum instead of
      autologous serum for culture. This modified method was used to culture additional
      biopsy specimens and genital ulcer scrapings from female and male patients,
      respectively. All monocyte co-cultures were examined by a rapid Giemsa (RapiDiff)
      stain and by an indirect immunofluorescence test with immune sera. Representative
      cultures were examined by transmission electron microscopy. C. granulomatis was
      successfully isolated in pure culture by the monocyte co-culture system from four
      biopsy specimens and 14 genital ulcer scrapings. The cultured organisms were
      visible both intra- and extra-cellularly and were extremely pleomorphic, with
      characteristic single and biopolar condensation. The numbers of the organisms
      increased after each passage. All positive cultures showed bright fluorescence
      when tested with immune sera. Transmission electron microscopy of the cultured
      bacteria demonstrated a typical gram-negative cell wall consisting of an outer
      membrane, middle electron opaque layer and an inner plasma membrane. The capsule
      was thick and electron dense. Numerous electron dense granules were present
      within the cytoplasm.

PMID- 9236743
TI  - Recognition of tissue cyst-specific antigens in reactivating toxoplasmosis.
AB  - Current serological tests do not discriminate between asymptomatic latent
      Toxoplasma gondii infection and reactivating toxoplasmosis, but timely
      therapeutic intervention before the development of symptoms would lead to major
      reductions in morbidity and permanent disability. This study developed a new
      enzyme-linked immunosorbent assay (ELISA) for antibody to T. gondii tissue cyst
      antigens and screened tissue cyst antigens by Western blot analysis to test the
      hypothesis that antibody recognition of T. gondii tissue cyst-derived antigen is
      a good indicator of reactivation disease. A total of 187 sera was tested by Sabin
      Feldman dye test and tissue cyst ELISA, AIDS patients and patients with ocular
      disease were considered separately, as the exposure to parasite antigens may be
      different in these two groups. The dye test did not discriminate between
      immunocompetent and immunocompromised T. gondii seropositive patients or between
      active and quiescent toxoplasmosis. Tissue cyst ELISA demonstrated a raised
      specific antibody response in immunocompetent T. gondii seropositive patients and
      in quiescent HIV positive sera. These data support th view that the tissue cyst
      population is in a state of dynamic equilibrium. It is proposed that, in the
      immunocompetent host, tissue cyst development and rupture are under some degree
      of immune control, but that in the immunocompromised host this equilibrium is
      disturbed and reactivation disease results. Data from patients with reactivating
      ocular toxoplasmosis demonstrate that tissue cyst-specific antibody levels are
      not different in active and quiescent disease and indeed they are not
      significantly different from immunocompetent T. gondii seronegative sera. In the
      Western blot analysis of 57 HIV positive patient sera, eight antigens (65, 57,
      49, 47, 36, 28, 26 and 18 kDa) were consistently recognised by one third or more
      of the sera tested, but no single antigen was diagnostic of quiescent or active
      toxoplasmosis. It is concluded that tissue cyst-derived antigens are not a
      reliable serological marker of reactivating toxoplasmosis.

PMID- 9236744
TI  - Evaluation of different techniques in the diagnosis of Toxoplasma encephalitis.
AB  - This study evaluated the detection of antibodies, circulating antigens and
      parasite DNA by polymerase chain reaction (PCR) in the diagnosis of toxoplasma
      encephalitis. The detection of antibody classes and IgG avidity were not useful
      diagnostically. The detection of circulating antigens by the ELISA system
      described was not sufficiently sensitive. The detection of DNA by PCR was the
      most useful test especially in untreated patients, with a sensitivity of 62%
      overall, 81% in untreated patients and only 20% in treated patients. The use of
      non-isotopic probes makes the use of this technique feasible in routine
      diagnostic parasitology laboratories.

PMID- 9236745
TI  - Identification by monoclonal antibodies of serotype D strains of Pasteurella
      multocida representing various geographic origins and host species.
AB  - Two outer-membrane proteins (OMPs) of Pasteurella multocida serotype D,
      designated H and W, possess potentially important serotype D-specific antigens.
      Antigenicity as well as toxigenicity of 55 strains of P. multocida representing
      various serotypes, geographic origins and host species were studied by SDS-PAGE,
      enzyme-linked immunosorbent assay (ELISA), immunoblot and polymerase chain
      reaction (PCR) assays. Based on the electrophoretic mobility of protein H,
      different OMP patterns were observed within different capsular serotypes. Three
      monoclonal antibodies (MAbs) designated MT1, MT2 and MT3 were produced against H
      and W proteins of P. multocida in BALB/c mice. MAbs MT2 and MT3 reacted with two
      distinct epitopes on W protein of serotype D in competitive ELISA. MAb MT1
      reacted with all serotype D-I strains but not with D-II strains, whereas MAb MT2
      reacted with both serotype D-I and D-II strains in dot-ELISA and immunoblot
      assay. MAb MT3 reacted with all P. multocida strains belonging to different
      capsular serotypes in dot-ELISA. None of the MAbs reacted with other gram
      negative bacteria tested, indicating that protein H has a serotype D-I specific
      epitope and protein W has both serotype and species-specific epitopes. PCR assay
      was used to identify toxigenic strains of P. multocida; 92% of P. multocida
      strains possess both toxA gene and MAb MT2 reacting epitope, suggesting a strong
      association between MAb MT2 reacting epitopes and toxA gene. Rapid dot-ELISA with
      MAb was found to be specific, sensitive and easy to perform and thus suitable for
      routine serotyping of P. multocida serotype D strains which might be potentially
      pathogenic.

PMID- 9236746
TI  - Molecular epidemiology of Vibrio cholerae O1 isolates from Colombia.
AB  - A total of 173 Vibrio cholerae O1 isolates from the recent cholera epidemic in
      Colombia was analysed by the polymerase chain reaction (PCR) for the genes
      encoding the A subunit of cholera toxin (ctxA) and the zonula occludens toxin
      (zot), and by ribotyping. All isolates were positive for ctx A and zot, which was
      confirmed by hybridisation. Ribotyping with restriction endonuclease Bg/I
      digestion of total DNA revealed three ribotypes: B5a comprising 165 (96.4%)
      isolates, and two new designated ribotypes B20 and B21a in six (3.5%) isolates
      and two (1.1%) isolates, respectively. These findings have significant public
      health implications.

PMID- 9236747
TI  - Phenotypic and genotypic discrimination of strains of Salmonella serotype
      Eimsbuettel from human and animal sources.
AB  - One hundred isolates of Salmonella serotype Eimsbuettel from various human,
      animal and environmental sources in six countries were typed and shown to belong
      to five ribotypes, five biotypes and eight different ribotype/biotype groups, one
      of which, ribotype 3/biotype 5, was represented among isolates from all six
      countries. Most of the Eimsbuettel isolates from Scotland belonged to ribotype
      1/biotype 3, which was the epidemic strain involved in a large outbreak centred
      in a Glasgow maternity hospital in 1986. That strain was also responsible for
      almost all the human infections that occurred in the west of Scotland in the
      years of this study. However, isolates from human cases in the east of Scotland
      belonged to either ribotype 2/biotype 1 or ribotype 3/biotype 5, groups not found
      in the west of Scotland. Representatives of all three ribotype/biotype groups
      causing human infection in Scotland were also found among isolates from poultry
      or poultry-associated materials. Plasmids were carried by only 14% of isolates
      and so provided little additional strain discrimination. However, plasmid
      analysis suggested that Salmonella Eimsbuettel of ribotype 2/biotype 1 had the
      potential to enter the human food chain in the UK via meat or bone meal, animal
      feed and poultry.

PMID- 9236749
TI  - Rising prescription drug costs: whose responsibility?

PMID- 9236748
TI  - Analysis of the mechanism of quinolone resistance in nalidixic acid-resistant
      clinical isolates of Salmonella serotype Typhimurium.
AB  - Over a period of 2.5 years, 42 cases of gastro-enteritis caused by nalidixic acid
      resistant Salmonella serotype Typhimurium occurred in Malaga. The epidemiological
      relationship among the strains involved was investigated by analysis of plasmid
      profile and of chromosomal DNA by pulsed-field gel electrophoresis (PFGE).
      Despite having different plasmid profiles, all 42 nalidixic-acid resistant
      Typhimurium isolates had evolved from one clone as shown by analysis of
      chromosomal DNA by PFGE. The mechanism of quinolone resistance in these
      Typhimurium isolates was also investigated. Analysis of outer-membrane proteins
      and lipopolysaccharide from quinolone-susceptible and resistant clinical isolates
      tested showed no differences. All nalidixic acid-resistant isolates had MICs for
      ciprofloxacin of 0.25 mg/L and for nalidixic acid of 1024 mg/L. Polymerase chain
      reaction fragments of 285 bp, containing the quinolone resistance-determining
      region of the gyrA gene, and of 237 bp, containing the region of parC homologous
      to the quinolone resistance-determining region of the gyrA gene, were sequenced.
      All resistant isolates presented a change at Ser-83 to Phe in the GyrA protein,
      but no changes were observed in the ParC protein. These findings indicated that
      this mutation in gyrA plays a major role in the acquisition of nalidixic-acid
      resistance in clinical isolates of Typhimurium.

PMID- 9236750
TI  - Thanksgiving day for the gift of life.

PMID- 9236751
TI  - Role of opioids in chronic non-cancer pain.

PMID- 9236752
TI  - Reduction in length of hospital stay for acute childhood asthma associated with
      the introduction of casemix funding.
AB  - OBJECTIVE: To examine changes to hospital admission rates, length of stay (LOS),
      bed use, and unplanned readmission rates for children with acute exacerbations of
      asthma following the change of the Victorian health care system to casemix
      funding. SETTING: Large university-affiliated children's hospital in Melbourne,
      Victoria. DESIGN: Prospective collection of data from July 1989 to June 1996 for
      all children admitted with acute asthma (n = 11939). RESULTS: The number of
      admissions for acute asthma showed a rising trend before the introduction of
      casemix funding in July 1993, and subsequently fell. There was a significant fall
      in mean LOS (64.5 to 39 hours; -40%; P = 0.001), and hence in bed-hours occupied
      for asthma (115370 to 61116; -47%; P = 0.001). There were no increases in
      unplanned readmission rates for asthma within the next seven or 14 days.
      CONCLUSION: LOS and bed use for acute asthma at our hospital have been
      significantly reduced since the introduction of casemix funding, although this
      study does not prove a causal relationship. There was no increase in readmission
      rates, and thus no suggestion of any adverse effects as a result of reducing LOS.
      The 47% reduction in bed-hours should lead to large reductions in cost to the
      hospital.

PMID- 9236753
TI  - The extent of undiagnosed gestational diabetes mellitus in New South Wales.
AB  - OBJECTIVES: To estimate the number of pregnant women in New South Wales who had
      not been tested for gestational diabetes mellitus (GDM) during the period 1991
      1994. DESIGN: The number of women not tested for GDM was estimated from the
      recorded data available in the NSW Midwives Data Collection (MDC) annual reports
      and compared with three incidence surveys. MAIN OUTCOME MEASURE: The number of
      pregnant women not tested for GDM. RESULTS: Over the four-year period, the
      average annual recorded MDC incidence of GDM was 2.2%. This percentage was
      adjusted up to 3.3% after review of the MDC validation study and an incidence
      study. However, the expected incidence of GDM from three incidence surveys was
      6.6%. Thus, half of the pregnant women in NSW do not appear to have been tested
      for GDM. CONCLUSION: For the four-year period 1991-1994, an-estimated 50% of
      women in NSW were probably not tested for GDM.

PMID- 9236754
TI  - Incidence of bloodborne virus infection and risk behaviours in a cohort of
      injecting drug users in Victoria, 1990-1995.
AB  - OBJECTIVE: To assess changes in risk behaviours for transmission of bloodborne
      viruses and incidences and prevalences of these viruses in a field-recruited
      cohort of injecting drug users. DESIGN: Prospective longitudinal cohort study.
      SETTING: Metropolitan and rural Victoria, June 1990 to December 1995. SUBJECTS:
      626 current injecting drug users (i.e., who had injected drugs within the
      previous 12 months). MAIN OUTCOME MEASURES: Seroconversion to HIV and hepatitis B
      and C viruses (HBV and HCV), risk behaviours for infection. RESULTS: HIV
      incidence was very low (0.2 per 100 person-years). HCV incidence was high (10.7
      per 100 person-years), but fell throughout the study, although the downward trend
      did not reach statistical significance. HBV incidence was moderate (1.8 per 100
      person-years) and did not fall. Prevalence of risk behaviours, notably sharing
      needles and syringes, decreased significantly. CONCLUSIONS: Significant change
      has occurred in the risk behaviours of the cohort, confirming results of cross
      sectional studies of injecting drug use. This change may be responsible for the
      apparent decline in HIV and HCV incidence. Further studies are needed to monitor
      the incidence of bloodborne viruses in injecting drug users. Efforts to decrease
      risk of transmission should continue.

PMID- 9236755
TI  - Glomerulonephritis secondary to Barmah Forest virus infection.
AB  - Clinical infection with Barmah Forest virus (BFV) is becoming increasingly
      recognised with serological testing. We report the first case of
      glomerulonephritis after BFV infection. The patient required diuretic and
      antihypertensive therapy, but made an almost complete recovery. BFV infection
      should be considered in the differential diagnosis of glomerulonephritis.

PMID- 9236756
TI  - Australian trends in opioid prescribing for chronic non-cancer pain, 1986-1996.
AB  - OBJECTIVE: To identify trends in the use of opioid drugs for chronic non-cancer
      pain. DESIGN: Review of three sets of official records-the record of Schedule 8
      (S8) opioid drugs used in Australia, 1984-1995, from the national Department of
      Health, Housing and Community Services; New South Wales Department of Health
      statistical summaries of the number of authorities to prescribe S8 drugs for
      cancer pain and non-cancer pain for each June from 1990 to 1996; and NSW
      Department of Health patient records for a cohort of patients first prescribed S8
      drugs in 1991. MAIN OUTCOME MEASURES: Total quantities of opioids used in
      Australia; numbers of S8 authorities issued in NSW. Outcome measures for the
      cohort study were the proportion of patients remaining on opioids long-term, the
      proportion for whom dose escalated over time, and the diagnoses for which opioids
      were being prescribed. RESULTS: Between 1986 and 1995, the amount of oral
      morphine used in Australia rose from 117 to 578 kg. Use of all other oral S8
      opioids combined increased from 93 to 149 kg. In NSW, the number of authorities
      to prescribe for non-cancer pain rose from 3326 in June 1990 to 5743 in June 1996
      (73% increase), while cancer pain authorities rose from 2652 to 4831 (82%
      increase). Sixty-nine of the 102 patients ceased to receive drugs on authority
      over the five year follow-up. These subjects received opioids for a mean of 19
      months. Among the remaining 33 subjects, dose escalation was common. Diagnostic
      information indicated that may patients had significant psychological and social
      problems. CONCLUSIONS: There has been a dramatic increase in opioid prescribing,
      a substantial proportion of which is for non-cancer pain. In a sample of patients
      being treated for non-cancer pain, long term use and dose escalation occurred in
      one third of cases.

PMID- 9236758
TI  - Inhibitors of the renin-angiotensin system.

PMID- 9236757
TI  - The use of oral opioids in patients with chronic non-cancer pain. Management
      strategies.
AB  - BACKGROUND: The use of oral opioids in non-cancer pain is increasing, but it is
      not clear that this is improving outcomes for patients. These management
      strategies were developed as a consensus view between the two authors, who are
      both Directors of the Australian Pain Society. The strategies were subsequently
      reviewed and approved by the other Directors of the Society: four anaesthetists
      specialising in pain management, a pharmacist, a rheumatologist, two
      rehabilitation physicians and an occupational therapist. EVIDENCE BASE: A MEDLINE
      search of the literature since 1966 produced 163 relevant articles, including two
      randomised controlled trials of oral opioids in non-cancer pain. MANAGEMENT
      CONSENSUS: A small group of patients with chronic non-cancer pain can benefit
      from the use of oral opioids. Thorough attention to diagnosis and patient history
      must precede any decision to prescribe opioids. Patients should be
      psychologically stable. Patient and doctor should-agree beforehand on how to
      assess the outcome of therapy. Only one doctor (the patient's regular primary
      carer or pain specialist) should prescribe opioids and assess the response.
      Sustained release morphine preparations are the drug of choice. A trial of
      therapy, with goals and endpoint agreed between patient and doctor, should
      precede any decision to prescribe opioids in the long term.

PMID- 9236759
TI  - Lower respiratory tract infection.

PMID- 9236760
TI  - Gestational diabetes ad nauseam.

PMID- 9236761
TI  - Confidentiality and the AMA's new code of ethics.

PMID- 9236762
TI  - Dirofilariasis with conjunctival inflammation.

PMID- 9236763
TI  - Ethics committees and bureaucracy.

PMID- 9236764
TI  - Overdose of venlafaxine--a new antidepressant.

PMID- 9236765
TI  - Severe envenomation by the taipan (Oxyuranus scutellatus)

PMID- 9236766
TI  - The effect of species and geographical origin of snakes on the identification of
      their venom using a commercial assay.

PMID- 9236767
TI  - Telemedicine: solution or problem?

PMID- 9236768
TI  - The prevention and management of osteoporosis. Consensus statement. Australian
      National Consensus Conference 1996.

PMID- 9236769
TI  - Structure and role in symbiosis of the exoB gene of Rhizobium leguminosarum bv
      trifolii.
AB  - The Rhizobium leguminosarum bv trifolii exoB gene has been isolated by
      heterologous complementation of an exoB mutant of R. meliloti. We have cloned a
      chromosomal DNA fragment from the R. leguminosarum bv trifolii genome that
      contains an open reading frame of 981 bp showing 80% identity at the amino acid
      level to the UDP-glucose 4-epimerase of R. meliloti. This enzyme produces UDP
      galactose, the donor of galactosyl residues for the lipid-linked oligosaccharide
      repeat units of various heteropolysaccharides of rhizobia. An R. leguminosarum bv
      trifolii exoB disruption mutant differed from the wild type in the structure of
      both the acidic exopolysaccharide and the lipopolysaccharide. The acidic
      exopolysaccharide made by our wild-type strain is similar to the Type 2
      exopolysaccharide made by other R. leguminosarum bv trifolii wild types. The
      exopolysaccharide made by the exoB mutant lacked the galactose residue and the
      substitutions attached to it. The exoB mutant induced the development of abnormal
      root nodules and was almost completely unable to invade plant cells. Our results
      stress the importance of exoB in the Rhizobium-plant interaction.

PMID- 9236770
TI  - The Drosophila ribosomal protein L14-encoding gene, identified by a novel Minute
      mutation in a dense cluster of previously undescribed genes in cytogenetic region
      66D.
AB  - The Minute phenotype results from mutations at > 50 loci scattered throughout the
      genome of Drosophila. Common traits of the Minute phenotype are short and thin
      bristles, slow development, and recessive lethality. Here, we report a novel P
      element induced Minute mutation, P?lacW? M(3)66D1, that maps to region 66D on
      chromosome 3L. Flies heterozygous for P?lacW? M(3)66D1 have a strong Minute
      phenotype. Molecular characterisation of the chromosomal region revealed three
      previously undescribed Drosophila genes clustered within a 5-kb genomic fragment.
      Two of the genes have significant sequence homology to genes for the mammalian
      ribosomal proteins L14 and RD, respectively, and share a joint 240-bp promoter
      region harbouring the P-element insert. Quantitative Northern blot analyses
      showed the mutation to affect RPL14 mRNA levels only. Interestingly, the
      reduction in abundance of RPL14 mRNA is not constitutive, indicating that the
      promoter function abolished by the inserted P-element is utilised with different
      efficiencies in different developmental situations. Remobilisation of the P
      element produced wild-type flies with normal levels of RPL14 mRNA, demonstrating
      that the mutant phenotype is caused by the insertion. P?lacW? M(3)66D1 joins a
      growing list of Minute mutations associated with ribosomal protein
      haploinsufficiency.

PMID- 9236771
TI  - Primary structure, sequence analysis, and expression of the thermostable D
      hydantoinase from Bacillus stearothermophilus SD1.
AB  - The gene coding for the thermostable D-hydantoinase from the thermophilic
      bacterium Bacillus stearothermophilus SD1 was cloned and its nucleotide sequence
      was completely determined. The D-hydantoinase protein showed considerable amino
      acid sequence homology (20-28%) with other hydantoinases and functionally related
      allantoinases and dihydroorotases. Strikingly the sequence of the enzyme from B.
      stearothermophilus SD1 exhibited greater than 89% identity with hydantoinases
      from thermophilic bacteria. Despite the extremely high amino acid homology among
      the hydantoinases from thermophiles, the C-terminal regions of the enzymes were
      completely different in both sequence and predicted secondary structure, implying
      that the C-terminal region plays an important role in determining the biochemical
      properties of the enzymes. Alignment of the sequence of the D-hydantoinase from
      B. stearothermophilus SD1 with those of other functionally related enzymes
      revealed four conserved regions, and five histidines and an acidic residue were
      found to be conserved, suggesting a close evolutionary relationship between all
      these enzymes.

PMID- 9236772
TI  - A soluble 12-kDa protein of the mitochondrial intermembrane space, Mrs11p, is
      essential for mitochondrial biogenesis and viability of yeast cells.
AB  - We have isolated an essential yeast gene termed MRS11, which codes for a soluble
      protein of the mitochondrial intermembrane space. Interestingly, this new gene
      shares many similarities with the previously characterized MRS5 gene: when
      expressed from a multicopy plasmid, MRS11 like MRS5 restores respiration
      competence to yeast strains defective in the splicing of mitochondrial group II
      introns. Both genes are essential for viability of yeast cells, as the disruption
      of either of them is lethal. The proteins encoded by MRS5 and MRS11, which
      display 35%, sequence identity are both located in the mitochondrial
      intermembrane space. Depletion of Mrs11p results in a phenotype similar to that
      observed in Mrs5p-depleted cells: accumulation of the precursor form of
      mitochondrial hsp60, inability to form spectrophotometrically detectable amounts
      of cytochromes and changes in the mitochondrial morphology. Although similar in
      sequence and function, Mrs5p and Mrs11p are not functionally equivalent and
      neither can substitute for the other, even when overexpressed. Taken together,
      our data suggest a cooperative mode of action of Mrs11p and Mrs5p in
      mitochondrial protein import or other related essential mitochondrial processes.

PMID- 9236773
TI  - The role of cysteine residues in the homeodomain protein Mat alpha 2 in mating
      type control of Saccharomyces cerevisiae.
AB  - The Mat alpha 2 homeodomain protein plays a pivotal role in the control of cell
      type in Saccharomyces cerevisiae. The homeodomain in the C-terminal region of Mat
      alpha 2 functions as a DNA-binding domain and the N-terminal region, containing
      two cysteine residues at positions 33 and 34, is thought to be involved in
      formation of Mat alpha 2 homodimers via disulfide bonds. mat alpha 2 mutants,
      isolated in a previous study, in which haploid-specific genes cannot be repressed
      by the Matal-Mat alpha 2 heterodimer but a-specific genes can be repressed by the
      Mat alpha 2 homodimer, were found to produce mutant Mat alpha 2 with a
      substitution of tyrosine or phenylalanine for Cys33. To clarify the role of Cys33
      and Cys34 in the Mat alpha 2 protein, we generated several mat alpha 2 mutants by
      site-directed mutagenesis which had serine residues in place of these Cys
      residues. Transforming MATa cells with plasmids carrying these mat alpha 2 (MAT
      alpha 1+) mutations rendered transformants unable to mate. Northern blot analysis
      revealed that transcription of the a-specific gene STE2 and the haploid-specific
      locus RME1 in these transformants is repressed to the same level as in wild-type
      MATa/MAT alpha cells. We concluded that neither Cys33 nor Cys34 is required for
      repression of a-specific genes by the Mat alpha 2 homodimer or of haploid
      specific genes by the Matal-Mat alpha 2 heterodimer, and therefore suggest that
      Mat alpha 2 homodimer formation in vivo is not mediated by disulfide linkage.

PMID- 9236774
TI  - Ammonium repression of the nitrite-nitrate (nasAB) assimilatory operon of
      Azotobacter vinelandii is enhanced in mutants expressing the nifO gene at high
      levels.
AB  - A number of Tn5 mutants were isolated which were unable to fix nitrogen and
      showed enhanced ammonium repression of the nitrate/nitrite assimilation genes.
      They also had reduced nitrate reductase activity under fully inducing conditions.
      Insertions were localized within the nifB gene, and inability to fix nitrogen was
      shown to be due to disruption of the nifB gene. However, enhanced ammonium
      repression proved to be the result of constitutive expression of the downstream
      nifO gene from an 'out' promoter present in Tn5. Our results suggest that
      molybdenum metabolism might function as a regulatory factor that acts through the
      nitrate reductase.

PMID- 9236775
TI  - Molecular cloning and characterization of the cDNA encoding the largest subunit
      of mouse RNA polymerase I.
AB  - We describe the cloning and analysis of mRPA1, the cDNA encoding the largest
      subunit (RPA194) of murine RNA polymerase I. The coding region comprises an open
      reading frame of 5151 bp that encodes a polypeptide of 1717 amino acids with a
      calculated molecular mass of 194 kDa. Alignment of the deduced protein sequence
      reveals homology to the beta' subunit of Escherichia coli RNA polymerase in the
      conserved regions a-h present in all large subunits of RNA polymerases. However,
      the overall sequence homology among the conserved regions of RPA1 from different
      species is significantly lower than that observed in the corresponding beta'-like
      subunits of class II and III RNA polymerase. We have raised two types of
      antibodies which are directed against the conserved regions c and f of RPA194.
      Both antibodies are monospecific for RPA194 and do not cross-react with subunits
      of RNA polymerase II or III. Moreover, these antibodies immunoprecipitate RNA
      polymerase I both from murine and human cell extracts and, therefore, represent
      an invaluable tool for the identification of RNA polymerase I-associated
      proteins.

PMID- 9236776
TI  - The two beta-lactamase genes of Streptomyces cacaoi, blaL and blaU, are under the
      control of the same regulatory system.
AB  - The production of beta-lactamase in Streptomyces cacaoi, which contains two beta
      lactamase-encoding genes, blaL and blaU, is inducible by beta-lactam compounds.
      The two genes have been cloned independently in S. lividans TK24, a beta
      lactamase-negative species. The blaU clone did not respond to the presence of
      beta-lactams, whereas the blaL clone appeared to be inducible in S. lividans. The
      latter clone contains two open reading frames, blaA and blaB, located just
      upstream of but transcribed divergently from blaL, which were shown to be
      required for the production as well as the induction of BlaL. The deduced BlaA
      protein belongs to the LysR family of transcription regulators. In order to
      examine the role of BlaA in regulation, we here report on over-expression of a
      GST-BlaA fusion protein in Escherichia coli and its use for antibody preparation.
      The GST-BlaA fusion protein was partially purified and bandshift assays showed
      that it bound the 197-bp blaL-blaA intergenic region. The BlaA DNA binding-site
      was further restricted to a 30-bp sequence containing a T-N11-A motif, a
      characteristic of LysR-type promoters. Another T-N11-A motif upstream of the blaU
      gene was also shown to bind BlaA. The affinities of these two T-N11-A motifs in
      BlaA binding were comparable. A plasmid bearing the blaU structural gene and the
      blaA-blaB regulatory region was constructed and shown to confer on an S. lividans
      host the capacity to produce inducible beta-lactamase. It can thus be concluded
      that the S. cacaoi blaL and blaU genes are controlled by the same regulatory
      system.

PMID- 9236778
TI  - A Darwinian theory for the origin of cellular differentiation.
AB  - In this theory, cell differentiation is a two-step mechanism at each stage of
      development. In the first step, gene expression is unstable. It occurs
      stochastically and produces different cell types. In the second step gene
      expression is stabilized by means of cellular interactions. However, this
      stabilization cannot occur until the combination of cell phenotypes corresponding
      to the developmental stage is expressed. This selection mechanism prevents
      disorganizing consequences of stochasticity in gene expression and directs the
      embryo towards the adult stage. Instability and stochasticity in gene expression
      are caused by random displacement of regulators along DNA, whereas
      phosphorylation and/or dephosphorylation of transcriptional regulators triggered
      by signal transduction between cells are responsible for the stabilization of
      stochastic gene expression. The origin of cellular differentiation is explained
      as an adaptation of cells to metabolic gradients created by substrate diffusion
      inside growing cell populations. This mechanism provides cells with complementary
      metabolism, increasing their ability to use food resources. Because the metabolic
      gradients are dependent on external substrate concentrations, cellular
      differentiation can also be viewed as an extension of natural selection inside
      organisms.

PMID- 9236777
TI  - Mutations in the heavy chain of cytoplasmic dynein suppress the nudF nuclear
      migration mutation of Aspergillus nidulans.
AB  - To identify proteins that interact directly or indirectly with the NUDF protein,
      which is required for nuclear migration in Aspergillus nidulans, we initiated a
      screen for extragenic suppressors of the heat-sensitive nudF6 mutation.
      Suppressor mutations in at least five genes, designated snfA-snfE, caused
      improved growth and nuclear migration at high temperatures compared to the nudF6
      parent. Two snfC mutations mapped near the nudA gene, which encodes the
      cytoplasmic dyncin heavy chain, and could be repaired by transformation with wild
      type nudA DNA, demonstrating that they are mutations in nudA. The snfC mutations
      are bypass suppressors of nudF and genetic evidence indicated that NUDA and NUDF
      act in the same nuclear migration pathway. Taken together, our data suggests that
      NUDF affects nuclear migration by acting on the dynein motor system.

PMID- 9236779
TI  - The Uba2 and Ufd1 proteins of Saccharomyces cerevisiae interact with poly(A)
      polymerase and affect the polyadenylation activity of cell extracts.
AB  - Poly(A) polymerase is responsible for the addition of the adenylate tail to the
      3' ends of mRNA. Using the two-hybrid system we have identified two proteins
      which interact specifically with the Saccharomyces cerevisiae poly(A) polymerase,
      Pap1. Uba2 is a homolog of ubiquitin-activating (E1) enzymes and Ufd1 is a
      protein whose function is probably also linked to the ubiquitin-mediated protein
      degradation pathway. These two proteins interact with Pap1 and with each other,
      but not with eight other target proteins which were tested in the two-hybrid
      system. The last 115 amino acids of Uba2, which contains an 82-amino acid region
      not present in previously characterized E1 enzymes, is sufficient for the
      interaction with Pap1. Both Uba2 and Ufd1 can be co-immunoprecipitated from
      extracts with Pap1, confirming in vitro the interaction identified by two-hybrid
      analysis. Depletion of Uba2 from cells produces extracts which polyadenylate
      precursor RNA with increased efficiency compared to extracts from nondepleted
      cells, while depletion of Ufd1 yields extracts which are defective in processing.
      These two proteins are not components of polyadenylation factors, and instead may
      have a role in regulating poly(A) polymerase activity.

PMID- 9236780
TI  - Gene targeting is locus dependent in the filamentous fungus Aspergillus nidulans.
AB  - The effect of altering the conditions of transformation on the efficiency of gene
      targeting in filamentous fungi was studied using Aspergillus nidulans as a model
      organism. The niaD and amdS genes of A. nidulans, which are both involved in
      nitrogen source utilisation, were selected as target loci. Homologous
      recombination of transforming DNA at these loci resulted in niaD and amdS mutants
      with an impaired ability to utilise nitrate or acetamide as the sole nitrogen
      source, respectively. Vectors were constructed that contained the Neurospora
      crassa pyr4 gene as a selectable marker and an internal segment of the amdS (0.6
      1.27 kb) or niaD (0.9-2.15 kb) genes. The parameters investigated for their
      effect on gene targeting included (a) length of homologous DNA in the disruption
      cassette, (b) conformation of the transforming vector (circular or linear), (c)
      transcriptional status (on/off) of the targeted gene, (d) concentration of DNA in
      the transformation mix and (e) temperature of incubation of the transformation
      reaction and of protoplast regeneration on selective media. Parameters shown to
      have an effect on the targeting frequency at the niaD locus were tested at the
      amdS locus. The level of gene targeting when circular DNA was used was found to
      correlate with the size of the homologous segment at both loci. Similarly the
      level of targeting was shown to increase when vectors were linearised within the
      region of homology. The level of targeting was unaltered at the niaD locus when
      transcription was induced at different stages in the transformation procedure.
      Likewise, targeting was unaffected by altering the amount of DNA in the reaction
      mix over the concentration range tested. The regeneration temperature did have an
      effect on targeting, with enhanced targeting observed at 25 degrees compared with
      37 degrees C. However, the most dramatic effect was the difference between
      targeting efficiency at different genetic loci, with targeting of niaD being at
      least five fold more efficient than amdS under all conditions tested.

PMID- 9236782
TI  - AAEM minimonograph #48: autonomic nervous system testing.
AB  - The autonomic nervous system maintains internal homeostasis by regulating
      cardiovascular, thermoregulatory, gastrointestinal, genitourinary, exocrine, and
      pupillary function. Testing and quantifying autonomic nervous system function is
      an important but difficult area of clinical neurophysiology. Tests of
      parasympathetic cardiovagal regulation include heart rate analysis during
      standing (the 30:15 ratio), heart rate variation with deep breathing, and the
      Valsalva ratio. Tests of sympathetic adrenergic vascular regulation include blood
      pressure analysis while standing, the Valsalva maneuver, sustained handgrip,
      mental stress, and cold water immersion. Tests of sympathetic cholinergic
      sudomotor function include the sympathetic skin response, quantitative sudomotor
      axon reflex test, sweat box testing, and quantification of sweat imprints. Pupil
      function is tested pharmacologically and with pupiilographic techniques. Tests of
      gastrointestinal and genitourinary function do not satisfactorily isolate
      autonomic regulation from their other functions. The available tests have various
      sensitivities and ease of administration. They are typically administered in a
      battery of multiple tests, which improves sensitivity and reliability, and allows
      probing of various autonomic functions.

PMID- 9236781
TI  - The Schizosaccharomyces pombe mam1 gene encodes an ABC transporter mediating
      secretion of M-factor.
AB  - In the fission yeast Schizosaccharomyces pombe, cells of opposite mating type
      communicate via diffusible peptide pheromones prior to mating. We have cloned the
      S. pombe mam1 gene, which encodes a 1336-amino acid protein belonging to the ATP
      binding cassette (ABC) superfamily. The mam1 gene is only expressed in M cells
      and the gene product is responsible for the secretion of the mating pheromone. M
      factor, a nonapeptide that is S-farnesylated and carboxy-methylated on its C
      terminal cysteine residue. The predicted Mam1 protein is highly homologous to
      mammalian multiple drug-resistance proteins and to the Saccharomyces cerevisiae
      STE6 gene product, which mediates export of a-factor mating pheromone. We show
      that STE6 can also mediate secretion of M-factor in S. pombe.

PMID- 9236783
TI  - Firing rate of the lower motoneuron and contractile properties of its muscle
      fibers after upper motoneuron lesion in man.
AB  - We studied motor unit (MU) firing rate and contractile properties and myosin
      isoform composition of single muscle fibers after upper motoneuron lesion. Single
      MUs and surface electromyogram (EMG) were recorded during voluntary contractions
      and locomotion in the paretic (P) and nonparetic (NP) tibialis anterior (TA) of
      15 hemiparetics. P TA low-threshold MUs fired within the lower end of their
      normal range. High-threshold MUs fired below their normal range or were not
      recruited. Surface EMG was abnormally low and high in the P TA and NP TA,
      respectively. On muscle cross sections stained with histochemical methods, type I
      fibers represented 99.4%, 74.3% and 66.6% of NP, P, and control TA, respectively.
      P TA fibers expressing type I myosin heavy chain (MyHC) were smaller, weaker, and
      slower. In conclusion, low MU firing rate and activity in the P TA was associated
      with slower type I MyHC fibers, while increased activity in NP TA resulted in
      homogenous expression of type I MyHC.

PMID- 9236784
TI  - Contractile studies of single human skeletal muscle fibers: a comparison of
      different muscles, permeabilization procedures, and storage techniques.
AB  - The study of single muscle fibers has improved our understanding of muscle
      physiology and pathology. To compare three techniques for fiber preparation and
      storage, biopsies were obtained from the tibialis anterior and vastus lateralis
      muscles of a hemiparetic patient and a control subject. Single fibers were
      prepared with: (1) chemical skinning (CS) and storage at -20 degrees C; (2)
      chemical skinning followed by sucrose (SU) incubation and storage at -80 degrees
      C; or (3) freeze-drying (FD) and -80 degrees C storage. Cross-sectional area
      (CSA), resting, maximal (P0), and specific tension (P0/CSA), and maximum
      shortening velocity (V0) were determined in 189 cells. CSA was similar in all
      groups. Resting tension was higher and P0 and P0/CSA lower after FD. In general,
      V0 was the same in all groups. Our data suggest that CS and SU preserve the
      properties of single muscle fibers better than FD. SU may allow longer storage of
      fibers.

PMID- 9236786
TI  - Slowly conducting, low-threshold components of sensory nerve potentials in
      peripheral neuropathy: a microneurographic study.
AB  - By recording the averaged potential from a microelectrode inserted into the
      nerve, small late components of the sensory nerve action potential can be
      analyzed. We studied the thresholds of the late components in median nerves of 15
      normal subjects and 37 patients with peripheral neuropathies. Under normal
      conditions, the late components reflected the activities of small myelinated
      fibers which had high thresholds. In the patients with peripheral neuropathies, a
      part of the late components often had abnormally low thresholds, occasionally the
      lowest. The presence of low-threshold, late components was related to the
      pathologies of the different types of neuropathy and correlated with the numbers
      of regenerating clusters in sural nerve biopsies. These slowly conducting, low
      threshold components may originate from regenerating or remyelinating fibers, and
      therefore should have prognostic value.

PMID- 9236785
TI  - Degeneration of cocultures of spinal muscular atrophy muscle cells and rat spinal
      cord explants is not due to secreted factors and cannot be prevented by
      neurotrophins.
AB  - We have shown recently that cocultures of muscle cells from infantile spinal
      muscular atrophy (SMA) patients innervated by motoneurons of normal rat spinal
      cord explants undergo a degeneration process, suggesting that muscle may play a
      role in this atrophy, which previously has been considered to be a pure
      motoneuron disease. Conditional media of SMA cocultures did not affect control
      healthy nerve muscle cocultures. Conversely, conditioned media of control
      cocultures were unable to prevent degeneration of SMA cocultures. Moreover,
      neurotrophic factors, thought to be of help in motoneuron disease treatment, did
      not protect SMA cocultures from premature death. Our results suggest that the
      abnormal phenotype observed in nerve-muscle coculture (1) is not due to the
      release of a toxic factor nor to the lack of a secreted survival factor, and (2)
      does not respond to neurotrophin treatment.

PMID- 9236788
TI  - Decomposition-enhanced spike-triggered averaging: contraction level effects.
AB  - Decomposition-enhanced spike-triggered averaging (DE-STA) was applied to the
      vastus medialis muscle to examine size distributions of surface-detected motor
      unit action potentials (S-MUAPs) at various force levels. Using DE-STA, 15-20 S
      MUAPs were identified during 5%, 10%, 20%, and 30% of maximum voluntary
      contraction. Average S-MUAPs showed increase in peak to peak (and negative peak)
      amplitude with force (In microV): 5% = 37.9 +/- 6.1 (16.6 +/- 2.5), 10% = 44.0 +/
      4.0 (20.4 +/- 1.8), 20% = 80.7 +/- 9.3 (41.3 +/- 4.5), and 30% = 102.5 +/- 10.3
      (53.6 +/- 5.0). Test-retest variability of peak to peak (and negative peak
      amplitude) between repeated trials was 0.10 (0.14), 0.14 (0.14), 0.17 (0.15), and
      0.21 (0.20) at 5%, 10%, 20%, and 30% respectively. A relationship was found
      between the S-MUAP amplitude and force (r2 = 0.78, df = 90, F = 160, P < 0.001).
      Increase in average S-MUAP amplitude with force suggests that STA performed only
      at low levels of contraction may result in a biased sampling and small average S
      MUAP amplitudes.

PMID- 9236787
TI  - Detection of Borrelia burgdorferi DNA and complement membrane attack complex
      deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary
      Lyme disease.
AB  - We report a patient who developed a chronic sensory-motor polyneuropathy and a
      progressive myelopathy 4 years after a tick bite. An increased serum antibody
      titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis,
      although a concomitant cervical spondylosis probably contributed to spinal cord
      damage. Treatment with ceftriaxone resulted in a marked improvement of
      neuropathic symptoms, providing indirect evidence of spirochetal infection.
      Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural
      nerve confirmed the diagnosis, demonstrating that the spirochete localized in the
      peripheral nervous system. The presence of complement membrane attack complex
      deposits and macrophage infiltrates around epineurial vessels and within the
      endoneurium suggests that the neuropathy in our patient was immune-mediated.

PMID- 9236789
TI  - Effects of long-term low-dose methylprednisolone on rat diaphragm function and
      structure.
AB  - In animal studies, high dosages of corticosteroids cause changes in diaphragm
      structure and function. The present study was designed to investigate the effects
      of long-term low-dose methylprednisolone (MP) administration on rat diaphragm
      contractile properties and morphology. Thirty adult rats were treated with saline
      or MP (0.2 mg/kg/day s.c.) during 6 months. Contractile properties of isolated
      diaphragm strips, immunohistochemical characteristics analyzed by means of
      antibodies reactive with myosin heavy chain isoforms, and enzyme activities were
      determined in the diaphragm muscle. MP significantly reduced diaphragm force
      generation by -15% over a wide range of stimulation frequencies. The number of
      type IIb fibers was reduced by MP. There was a mild but significant decrease in
      type I and IIa fiber cross-sectional area (CSA), whereas type IIx and IIb CSA did
      not change. These changes resulted in a reduction in the relative contribution of
      type IIb fibers to total diaphragm muscle area. Biochemically, MP decreased
      glycogenolytic activity, while fatty acid oxidation and oxidative capacity were
      increased. In conclusion, long-term low-dose MP administration caused a marked
      impairment in diaphragm function. This is accompanied by changes in diaphragm
      muscle morphology and enzyme capacity.

PMID- 9236790
TI  - Time and frequency domain analysis of acoustic signals from a human muscle.
AB  - We wished to determine whether evoked force output from a human muscle could be
      inferred from the amplitude and the frequency of evoked muscular sounds. Sounds
      from adductor pollicis were recorded with a microphone and compared to evoked
      force changes produced by varying the intensity of nerve stimulation or of
      voluntary effort as well as by fatigue and twitch potentiation. In all instances,
      high correlations were obtained between evoked acoustic signals amplitude and
      evoked twitch force changes. Instantaneous time-frequency distributions of evoked
      acoustic signals also showed a high degree of cross correlation with evoked
      instantaneous twitch force, but no relationship was found for the group between
      the maximal frequency of sound and force changes. We conclude that evoked force
      changes from human muscles cannot be reliably inferred from frequency domain
      analysis of evoked sound signals and that, for this purpose, analysis of sound
      signals in time domain can be employed, an analysis potentially useful for
      muscles whose force output cannot be directly measured.

PMID- 9236791
TI  - Guillain-Barre syndrome in immunocompromised patients: a report of three patients
      and review of the literature.
AB  - Both humoral and cell-mediated autoimmune mechanisms have been implicated in the
      pathogenesis of Guillain-Barre syndrome (GBS). Therefore, its occurrence in
      severely immunocompromised patients is not expected. We identified 3 severely
      immunocompromised patients who developed GBS. Two of the 3 patients had acquired
      immunodeficiency syndrome with CD4 counts of 5 and 4 cells/mm3, respectively. One
      post-cardiac transplant patient was taking azathioprine and cyclosporine at the
      time of onset of GBS. In all 3 patients, immunocompromise was induced by
      infectious or chemotherapeutic agents which preferentially suppress T-lymphocyte
      responses. All 3 had severe lymphocytopenia and incomplete recovery. We conclude
      that GBS can occur in patients with severe t-cell suppression. Although no
      conclusion regarding prognosis can be drawn from our small group of patients,
      their incomplete recovery is consistent with the idea that T-cells are important
      for recovery.

PMID- 9236792
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy in children: I.
      Presentation, electrodiagnostic studies, and initial clinical course, with
      comparison to adults.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is rare in
      children. We reviewed features of 15 children with idiopathic CIDP, and compared
      these to 69 adults with idiopathic CIDP. Children demonstrated many similarities
      to adults: (1) Antecedent events were uncommon. (2) There was a high frequency of
      weakness and reflex loss, a relatively high frequency of sensory loss, and a low
      frequency of pain and cranial neuropathies. (3) Cerebrospinal fluid protein
      levels were usually elevated. (4) On electrodiagnostic testing, not all nerve
      segments were abnormal, and not all children satisfied electrodiagnostic criteria
      for CIDP. Children differed from adults with CIDP in several ways: (1) The onset
      of symptoms was usually more precipitous. (2) Gait abnormalities were a more
      frequent presenting symptom. (3) Children always presented with significant
      neurological dysfunction, and not with the minor symptoms initially seen in some
      adults. The initial response of children with CIDP to immunomodulating therapy
      was excellent.

PMID- 9236793
TI  - Regeneration-blocked mdx muscle: in vivo model for testing treatments.
AB  - We have refined the mdx mouse as a clinical model for Duchenne dystrophy. Our
      power estimates, primary measures, regular sacrifice intervals, and quality
      checks constitute a high-speed, low-cost system for preclinically testing
      therapies designed to slow muscle destruction in Duchenne dystrophy. Irradiated
      (18 Gy) and contralateral shielded anterior tibial muscles were studied in 21-day
      old mdx and normal mice at the time of irradiation and 4, 8, 12, 16, and 20 weeks
      thereafter. Regeneration-blocked mdx (irradiated) muscle expressed muscular
      dystrophy as progressive wasting after a brief (4 week) period of growth.
      Regeneration-blocked normal muscle showed stunted growth but neither progressive
      wasting nor microscopic pathological changes.

PMID- 9236794
TI  - Krabbe's disease presenting as a peripheral neuropathy.
AB  - A 13-year-old female initially presented with scoliosis and pes cavus. Initial
      examination revealed distal lower extremity weakness and sensory loss, as well as
      greater auricular nerve hypertrophy. There was a Babinski sign on the right.
      Nerve conduction velocities were consistent with a demyelinating neuropathy. Four
      years after initial presentation she developed lower extremity spasticity and
      bilateral Babinski signs. Magnetic resonance imaging of the brain showed diffuse
      white matter disease. Laboratory evaluation revealed an abnormally low
      galactocerebroside beta-galactosidase level. Nerve biopsy demonstrated inclusions
      consisting of globoid clusters and evidence of demyelination. DNA analysis was
      used to identify mutations consistent with Krabbe's disease. Patients presenting
      with an atypical peripheral neuropathy should be evaluated for Krabbe's disease.

PMID- 9236795
TI  - Noninvasive laser neurolysis in carpal tunnel syndrome.
AB  - The peripheral nervous system is photosensitive providing the scientific
      rationale for this study, which determines the efficacy and safety of laser light
      exposure in 30 cases with CTS. Nine joules of energy over five points (7-15
      treatments) reversed CTS in 77% of cases with three-fold normalization of CMAP. A
      photobiologic response was seen in 80% of nerves. This unique and novel approach
      is cost-effective and will play a role in future management of CTS.

PMID- 9236796
TI  - Long-term external calcium dependence of autotransplanted and sliced extensor
      digitorum longus muscle contractility.
AB  - Contractile responses were studied in autotransplanted and sliced extensor
      digitorum longus (EDL) muscles at different times after the surgical intervention
      (3 and 12 months). The contraction of autotransplanted and sliced EDL muscles
      remained strongly dependent upon the extracellular Ca2+ concentration ([Ca]o) 3
      and even 12 months after the intervention. It could be suggested that in
      autotransplanted and sliced EDL muscles, neural control could be involved in the
      persistent dependence of contractility toward [Ca]o.

PMID- 9236798
TI  - Novel measurement for automated interference pattern analysis of the diaphragm.
AB  - The automated interference pattern analysis for limb muscles was modified to take
      into account the unique features of the needle EMG of the diaphragm. The
      modification was successful in recording more accurately the number of small and
      large segments and the activity levels with inspiratory effort. "Clouds" were
      generated in ten healthy subjects. The techniques may prove useful in
      electrophysiological investigations.

PMID- 9236797
TI  - Marked improvement of severe polyneuropathy associated with multifocal
      osteosclerotic myeloma following surgery, radiation, and chemotherapy.
AB  - We describe a patient with a 3 year history of progressive polyneuropathy that
      rendered him severely quadriparetic and bedridden. Work up revealed an IgG lambda
      monoclonal spike and multifocal osteosclerotic myeloma. Remarkable improvement
      followed combined treatment with surgical excision, radiation therapy, and
      chemotherapy using chlorambucil, danazol, and hydrocortisone. Hence, we believe
      that aggressive local therapy associated with systemic chemotherapy should be
      considered in severely affected patients with multifocal osteosclerotic myeloma
      and peripheral neuropathy.

PMID- 9236799
TI  - Flexor digitorum superficialis: locations of individual muscle bellies for
      botulinum toxin injections.
AB  - Twenty-two Flexor Digitorum Superficialis (FDS) muscles from 18 cadavers were
      dissected to find the "Optimal Injection Site" (OIS) for botulinum toxin
      injections to individual bellies of FDS. Coordinates are given as a percentage of
      the distance along a landmarking line from the medial epicondyle to the pisiform
      and in millimetres (mm) lateral to it. The OIS were: FDS2: 72%, 14 mm; FDS3: 54%,
      17mm; FDS4: 49%, 7mm; FDS5: 76%, 6mm. OIS measurements guide the
      electromyographer to localize the targeted muscle belly.

PMID- 9236800
TI  - Selective posterior rhizotomy and constant-voltage stimulation.

PMID- 9236801
TI  - Increase of the early clinical diagnosis of carpal tunnel syndrome over the last
      twenty years.

PMID- 9236802
TI  - Cardiac hormones: diagnostic and therapeutic potential.

PMID- 9236803
TI  - The cost of campylobacteriosis in New Zealand in 1995.
AB  - AIM: To estimate the financial impact of campylobacter infection in Canterbury
      and New Zealand in 1995. METHODS: The records of Canterbury Health Laboratories
      and hospital notes were searched to locate all inpatients admitted with
      campylobacteriosis in Christchurch in 1995 and to determine the costs involved.
      Further estimates of costs of outpatient care and costs due to lost productivity
      were made using local notification data. The computer database was searched for
      all cases of Guillain-Barre syndrome and reactive arthritis in 1995, and an
      estimate made of the cost attributable to campylobacter. RESULTS: There were 65
      admissions for campylobacteriosis at a cost of $92,262. Notified cases in general
      practice were estimated to cost $61,911 and loss of work an additional $338,499.
      Of the eight admissions with Guillain-Barre syndrome in 1995, the estimated cost
      of cases due to campylobacter infection was $89,522. Inpatient costs of reactive
      arthritis were negligible. Overall costs in Canterbury in 1995 amounted to
      $582,194, with a corresponding national figure of $4.48 million. The true cost of
      campylobacter infection may be up to ten times higher. CONCLUSIONS: The current
      high incidence of campylobacter infection has considerable financial impact on
      the community. Further public health and research initiatives to decrease
      incidence and associated costs are encouraged.

PMID- 9236804
TI  - Sale of cigarettes to school children aged 14 and 15 years in New Zealand.
AB  - AIMS: To determine the sources of cigarettes and extent of illegal sales to 14
      and 15 year old children, and to examine associated risk factors in order to more
      effectively reduce tobacco access to children. METHOD: Nationwide cross sectional
      survey of fourth form school children in New Zealand by means of an anonymous
      self administered questionnaire. RESULTS: Questionnaires from 14,097 fourteen and
      fifteen years olds were analysed, with over one third smokers. Twenty four
      percent of the whole group (3432) had bought cigarettes in the last year. Of
      smokers, 59.9% bought their own, with the great majority (68.9%) from dairies,
      particularly females. Ninety five percent said it was "easy" or "very easy" to
      buy cigarettes, and this was a major risk factor for this behaviour (relative
      risk (RR) = 2.01, 95% confidence interval (CI) 1.74, 2.32, RR = 2.54, CI 2.28,
      2.83, respectively). Only 24.6% children had ever been refused cigarettes because
      of age and all points of sale were comparable in this respect. Heavy smokers and
      males were more likely to have been refused. While refusal was associated with a
      fourfold increase in the perception that it was difficult to buy cigarettes,
      there was only a minimal reduction in the risk of children buying their own
      cigarettes (RR = 0.95, CI 0.91, 1.00). CONCLUSION: We have shown that the illegal
      sale of cigarettes to children is unacceptably easy and accurately perceived as
      such by children who smoke. The active enforcement of existing or future
      legislation is essential, with prosecution of offending retailers, if we are to
      make any progress to reduce the high prevalence of smoking in New Zealand
      children.

PMID- 9236805
TI  - Body size of New Zealand Pacific Islands children and teenagers.
AB  - AIM: To describe the mean height, weight and body mass index of Pacific Islands
      children aged 5-18 years residing in New Zealand and compare them with
      international reference charts commonly used in New Zealand. METHODS: Data from
      three data sets were used, which included 816 children from most Pacific
      countries with measurements being obtained in Auckland and Wellington. Mean
      values and 95% confidence intervals were compared to National Center for Health
      Statistics (USA) standards for height and weight. RESULTS: The mean height of
      males and females was on about the 95th percentile from age 5 to about age 10-11.
      During the teenage years it moved to the 50th percentile. Mean weight remained
      close to the 95th percentile until the mid teens and then it fell below the 95th
      percentile later in the teenage years. CONCLUSION: Mean body height and weight of
      Pacific Islands children were very high compared with international standards
      especially between 5-12 years and new Polynesian standards need to be developed.

PMID- 9236807
TI  - Women with past history of bone fracture have low spinal bone density before
      menopause.
AB  - AIMS: Recent work from our laboratory has demonstrated that young girls with bone
      fractures have low spinal bone density more often than girls who have never
      fractured. This study was undertaken to determine whether adult women approaching
      menopause who have any past history of fracture have lower spinal density than
      women who have never fractured. METHODS: A lifetime fracture history was taken
      from all premenopausal women (n = 59) enrolled in a clinical trial examining the
      effect of menopause on cardiac risk. Bone mineral density of the lumbar spine was
      measured at study entry by dual energy x-ray absorptiometry (Lunar DPX-L) and
      results from patients with and without fracture were compared. RESULTS: Women
      with a previous history of fracture (n = 23) had significantly lower bone density
      (6% less) than the women who had never broken a bone (n = 36). CONCLUSIONS: We
      conclude that women who report a previous history of fracture, either as young
      adults or in childhood, should be targeted for perimenopausal screening for
      osteoporosis since they are likely to have lower bone density and a greater risk
      of future fracture than women with no past history of fracture.

PMID- 9236806
TI  - House dust mite and cat allergen levels in domestic dwellings in Christchurch.
AB  - AIMS: To quantify the levels of Dermatophagoides pteronyssinus allergen (Der p I)
      and Felis domesticus allergen (Fel d I) in domestic dwellings in Christchurch and
      to assess possible relationships with housing characteristics. METHODS: Domestic
      dwellings (n = 93) were randomly selected and housing characteristics documented
      during the summer of 1994/95. Dust samples were obtained from the floor of the
      living room (LR) and bedroom (BR) and from the bed by standard vacuuming methods.
      The predominant mite species were determined and D pteronyssinus and F domesticus
      levels quantified. RESULTS: D pteronyssinus was the predominant (95%) species. D
      pteronyssinus allergen levels [geomean (95% confidence intervals) were 3.5(2.5
      4.8) micrograms/g in LR, 10.1(7.5-13.7) micrograms/g in BR and 5.7(4.3-7.6)
      micrograms/g in the bed. F domesticus allergen levels were significantly higher
      (p < 0.001) in houses with cats than without cats [median (range) 93.2 (3.3
      1227.2) micrograms/g and 2.9 (0.4-214.8) micrograms/g respectively]. Higher LR D
      pteronyssinus allergen levels were found in houses classified as having high
      indoor humidity and in houses situated in geographically damp locations.
      CONCLUSIONS: Domestic D pteronyssinus and F domesticus allergen levels in
      Christchurch are comparable with those found in other climatically similar
      locations. D pteronyssinus allergen levels are associated with both indoor and
      outdoor humidity factors.

PMID- 9236808
TI  - Acute pain services in New Zealand hospitals; a survey.
AB  - AIM: To describe the services available for the treatment of acute pain in
      surgical hospitals in New Zealand. METHODS: A survey of all surgical hospitals in
      New Zealand was undertaken in 1994 by postal questionnaire, followed up by
      telephone when necessary for completeness or clarification. A subset of these
      hospitals was resurveyed in 1996. RESULTS: Completed questionnaires were obtained
      from 62 surgical hospitals (78% of the 79 surveyed). Of these, 38 operated within
      23 publicly funded crown health enterprises (CHEs), the remainder being privately
      funded institutions. A formal pain service, with designated medical and/or
      nursing time, was in operation in only 12 hospitals, all of which were larger
      institutions (150 beds or more) within CHEs. Informal pain services were in
      operation in 28 additional hospitals, including 8 of 24 private hospitals. Most
      hospitals employed a wide range of analgesic modalities, although epidural
      infusions and nerve block infusions were used in a greater proportion of
      hospitals with a formal acute pain service. By 1996 the number of hospitals with
      nursing and/or medical positions designated for acute pain management had
      increased. CONCLUSION: Most New Zealand surgical hospitals use a wide range of
      modern analgesic modalities and an increasing number are providing formal acute
      pain services with designated medical and/or nursing time.

PMID- 9236809
TI  - Aids to smoking cessation.

PMID- 9236810
TI  - Alkaptonuria with ochronotic nephropathy and multiple joint replacement for
      ochronotic arthropathy.

PMID- 9236811
TI  - Vasodepressor syncope in competitive cyclists.

PMID- 9236813
TI  - Self dosing with cobalt or selenium by farmers.

PMID- 9236812
TI  - Myocarditis, rhabdomyolysis and myoglobinuric renal failure complicating
      influenza in a young adult.

PMID- 9236814
TI  - Gastric emptying: gender differences.

PMID- 9236815
TI  - The emotions and asthma.

PMID- 9236816
TI  - Clinical research in the tropics.

PMID- 9236817
TI  - Reproductive and socio-economic correlates of maternal haemoglobin levels in a
      rural area of Papua New Guinea.
AB  - The effects of pregnancy, lactation, and socio-economic status on maternal
      haemoglobin levels among the Au, a foraging and small-scale horticultural
      population of Papua New Guinea, are examined. The sample consists of 259 parous
      women, 41 of whom reside in wage-earning households and 218 of whom reside in
      households practicing traditional subsistence activities. The haemoglobin level
      among the total sample averages an extraordinarily low 8.6 g/dl and the
      prevalence of anaemia as defined using current WHO standards is just over 98%.
      Wage-earning Au, however, have significantly higher haemoglobin levels and lower
      rates of anaemia than their traditional counterparts. Haemoglobin levels decline
      significantly during pregnancy by just over 1 g/dl among both socioeconomic
      groups, but soon return to pre-gravid levels postpartum. No significant effects
      of lactation on haemoglobin levels are found, nor does the population show any
      long-term, parity-specific trends in haemoglobin levels.

PMID- 9236818
TI  - Morbidity and mortality due to ascariasis: re-estimation and sensitivity analysis
      of global numbers at risk.
AB  - This paper presents estimates of the global numbers of people at risk from
      morbidity related to infection with Ascaris lumbricoides and the numbers of
      deaths from this infection. Morbidity is classified into 4 types: deficits in
      growth and fitness which are contemporaneous with infection, or permanent, overt
      acute illness of mild to moderate severity, and complications involving
      hospitalization. The estimation of morbidity is based on theoretical models of
      parasite distributions developed in previous papers. A sensitivity analysis is
      carried out in which parameters of the model are varied using a Latin hypercube
      sampling technique. The results estimate approximately 1300 million infections
      globally with 59 million at risk of some morbidity. The estimate for acute
      illness is 12 million cases per year with approximately 10,000 deaths. Most
      morbidity is in children. Sensitivity analysis suggests that infection estimates
      will not vary greatly with changes in parameter values but that morbidity
      estimates may be highly variable.

PMID- 9236819
TI  - Gender and ethnic differences in onchocercal skin disease in Oyo State, Nigeria.
AB  - During preparation for a study on the effects of ivermectin treatment on
      onchocercal skin disease in the Ifeloju Local Government Area of Oyo State,
      Nigeria, 1032 adults aged 20 years and older were examined for skin lesions and
      palpable nodules. It was found that for 4 types of skin lesions, acute papular
      onchodermatitis (APOD), chronic papular onchodermatitis (CPOD), lichenified
      onchodermatitis (LOD) and depigmentation (leopard skin), as well as for
      subcutaneous nodules, females had a significantly higher prevalence than males.
      Although the area is inhabited primarily by the Yoruba people, the study also
      included some of the cattle-herding Fulani ethnic group. The reactive skin
      lesions, APOD, CPOD and LOD, were found to be more common among the Fulani,
      although there were no significant differences in leopard skin and nodules
      between both groups. While there is need for further research on both
      immunological and behavioural factors that may lead to these differences in
      disease. The need to achieve equity in health programming by ensuring that women
      and ethnic minorities receive full disease control services is of more immediate
      concern.

PMID- 9236820
TI  - Antifilarial activity of a synthetic marine alkaloid, aplysinopsin (CDRI Compound
      92/138).
AB  - CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in
      experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodon
      hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed
      63.8 and 90% of adult L. carinii and A. viteae at doses of 30 and 50 mg/kg (i.p.)
      respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the
      compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae,
      respectively. At 200 mg/kg administered orally on days 0, 10 and 25 post
      infection, it reduced establishment of adult A. viteae by 68.5%. We also found
      43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a
      single dose of 250 mg/kg, p.o. The compound was active in vitro at 100
      micrograms/ml concentration and caused a significant decline in MTT reduction and
      14C-glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could
      provide a new pharmacophore for the development of antifilarial agents.

PMID- 9236821
TI  - Trial of the ParaSight-F test for malaria diagnosis in the primary health care
      system, Zimbabwe.
AB  - Rapid diagnosis of Plasmodium falciparum malaria remains one of the main
      limitations to prompt treatment. Diagnosis based on clinical symptoms is
      decidedly unreliable, especially in areas of seasonal transmission like Zimbabwe.
      In view of this, the Plasmodium falciparum histidine rich protein (HRP-II)
      antigen detection assay (ParaSight-F test) was tried at 10 health centres in 3
      malaria endemicity zones of Zimbabwe, as a malaria diagnostic tool for primary
      health care. Parasitological evaluations were conducted using thick and thin film
      microscopy as gold standard, and ease of test operation and practicability to
      nurses were ascertained by questionnaire. The sensitivity of the test did not
      vary substantially by endemicity zone and was approximately 93%. Specificities
      were 85, 72 and 92% in the hyperendemic, mesoendemic and hypoendemic zones,
      respectively. Positive predictive values varied considerably with endemicity, the
      lowest being in the hypoendemic zone (56%). However, negative predictive values
      did not change significantly, with a mean of 94%. It was found that the ParaSight
      F test reduced mistreatment for malaria, relative to clinical diagnosis, by up to
      81%, especially in the hypoendemic region. Test acceptability evaluations were
      good.

PMID- 9236822
TI  - Detection of the circulating antigens CAA and CCA in a group of Dutch travellers
      with acute schistosomiasis.
AB  - Detection of circulating anodic antigen (CAA) and circulating cathodic antigen
      (CCA) in serum and urine is a highly specific and sensitive alternative for the
      diagnosis of schistosome infections in endemic areas. However, it is not known
      how soon after the onset of infection these antigens can be detected in humans.
      Neither has there been much research on the detection of these antigens in
      individuals normally living in non-endemic areas. We studied the kinetics of CAA
      and CCA in serum and urine of a group of 28 Dutch tourists, shortly after
      accidental exposure to a Schistosoma infection during a visit to Mali. Twenty
      seven were found to be positive for Schistosoma eggs and/or specific antibodies.
      From each individual, 1-4 serum samples were tested for circulating antigen
      level, 4-15 weeks after exposure, and urine samples were also tested from 22
      subjects. CAA and CCA levels were quantified by monoclonal antibody-based ELISAs
      and TRIFMAs. In serum, 23 individuals (85%) were positive at least once for one
      or both antigens, but titres were generally very low. CAA and CCA could be
      detected 5 and 6 weeks after exposure, respectively. Urines were all found to be
      negative. Almost all cases were negative at 7 months' follow-up.

PMID- 9236824
TI  - Higher resistance to Plasmodium falciparum infection in patients with homozygous
      sickle cell disease in western Kenya.
AB  - Sickle haemoglobin (HbS) is considered to be protective against malaria. Malaria
      is fatal in homozygous sickle cell (HbSS) disease. In a cross-sectional survey by
      alkaline. Hb-electrophoresis of 766 residents of Western Kenya near Lake
      Victoria, 20 were found to have HbSS disease, 120 sickle cell trait (HbAS) and
      626 the normal genotype (HbAA). Blood slides for malarial parasites (MPs) were
      performed in 728 cases, i.e. 592 HbAAs, 116 HbASs and all 20 HbSSs. Malaria
      parasites were found in 261 (35.8%) HbAAs, 42 (5.8%) HbASs and 4 (0.5%) HbSSs.
      Malaria prevalences per genotypic group were 44.1% (261 out of 592) in HbAAs,
      36.2% (42 out of 116) in HbASs, and 20% (4 out of 20) in HbSSs. The relative risk
      of malarial infection was 0.33 in the HbSSs compared to both HbAAs and HbASs. It
      seems that the protection conferred by HbS against malaria is more marked in HbSS
      disease than in HbAS and is HbS-content related, and that the balanced
      polymorphism in the HbS-malaria relationship is maintained-by higher mortality
      risk of HbAAs due to malaria and high mortality risk of HbSSs caused by
      complications of HbSS.

PMID- 9236823
TI  - The aetiology of low birthweight in a rural area of Tanzania.
AB  - In a hospital-based study, birthweights of 3162 consecutive births were related
      to perinatal mortality, multiple birth, and gestational age. Independent
      associations between 15 potential determinants and low birthweight, prematurity
      and small-at-term factors were also assessed. A newly constructed local curve of
      birthweight-for-gestational age is compared with the existing curves. The
      variables positively associated with low birthweight (< 2500 g) were nulliparity,
      vomiting as a self-reported complaint, spleen enlargement, sex of the infant and
      previous perinatal mortality. Nulliparity and spleen enlargement were positively
      associated with preterm birth, while small-at-birth was mostly associated with
      nulliparity and sex of the infant. Further study on spleen enlargement, the only
      modifiable factor in this study of possible public health importance, is
      warranted. Other factors of potential importance which deserve further
      investigations are hard physical work, maternal morbidity and antenatal care.

PMID- 9236825
TI  - Selenium status in pregnant women of a rural population (Zaire) in relationship
      to iodine deficiency.
AB  - Endemic myxoedematous cretinism has been associated with combined selenium and
      iodine deficiency in several areas of Zaire. To determine selenium and iodine
      status across the country, serum selenium and thyroid function parameters
      including urinary iodide were determined at prenatal clinics in 30 health centres
      of rural villages distributed over the whole country. Only in Bas-Zaire was the
      mean serum selenium level similar to that in non-deficient areas (80-120 ng/ml);
      in the regions of Bandunda and Kasai levels were marginally decreased (55-80
      ng/ml), and in Kivu, Haut-Zaire, Equateur and Shaba they were marginally or
      moderately decreased (< 55 ng/ml). The frequency of abnormally low urinary iodide
      (< 5 micrograms/dl) varied from 20% in the region of Bas-Zaire to 50% in Kasai (P
      < 0.001), and to still higher percentages in the 5 other regions of Zaire
      (Bandundu, 57%; Kivu, 63%; Equateur, 72%; Shaba, 76%; Haut-Zaire, 84%). With the
      exception of Bas-Zaire, biochemical maternal hypothyroidism (serum TSH > 5mU/l)
      was present in every region, with a frequency ranging from 3% in Kivu to 12% in
      Equateur. Iodine deficiency affects most of the Zairean population and requires
      public health measures on a larger scale than previously estimated. Combined
      iodine and selenium deficiency affects Equateur, Haut-Zaire and Kivu, where
      endemic myxoedematous cretinism occurs, but also Shaba, where it was not
      previously described. Besides combined iodine and selenium deficiency which is
      permissive, another factor (thiocyanate?) must be taken into account to explain
      the peculiarly elevated prevalence of endemic myxoedematous cretinism in Central
      Africa.

PMID- 9236826
TI  - Plasmodium falciparum chloroquine and quinine sensitivity in asymptomatic and
      symptomatic children in Sao Tome Island.
AB  - Plasmodium falciparum sensitivity to quinine in Sao Tome was determined by in
      vivo and in vitro tests in 56 children with mild or cerebral malaria. Chloroquine
      sensitivity was assessed by in vitro tests in 105 parasitaemic asymptomatic
      children from the same community as the cases. The WHO standard methodology was
      used. No resistance to quinine was found by in vivo or in vitro tests in either
      group of patients or in asymptomatic children, although some degree of
      chloroquine resistance was found with the in vitro test. This was more common in
      patients than in asymptomatic children. Chloroquine resistance may be explained
      by the recent history of malaria in Sao Tome Island, which caused an important
      decrease of immunity among the population and consequently the emergence of
      resistant strains. Implications of the use of in vivo/in vitro tests for
      determining the antimalarial drug policy within the primary health care system
      are discussed.

PMID- 9236828
TI  - Viral haemorrhagic fevers in ancient Mesopotamia.

PMID- 9236827
TI  - Operational aspects of bednet impregnation for community-based malaria control in
      Nicaragua, Ecuador, Peru and Colombia.
AB  - Community intervention projects with pyrethroid (permethrin and
      lambdacyhalothrin) impregnated bednets and an accompanying community education
      programme were carried out in 6 malaria endemic areas on the Pacific coast of
      Nicaragua, Ecuador, Peru and Colombia as well as in the Peruvian Amazon basin. In
      this paper the operational aspects are analysed: bednet coverage, results of
      promotional activities for increased bednet use, the sale of low-cost bednets,
      techniques and difficulties with impregnation, acceptance of the programme
      (including washing of impregnated nets), side-effects, residual concentrations of
      the chemical in the nets, costs of the impregnation programme and insecticide
      resistance of the malaria vectors. We found that the local manufacture of bednets
      and their sale through village health workers, even in communities with low cash
      income, is a viable way of increasing bednet coverage; the impregnation of
      bednets is well accepted if villagers perceive a direct benefit; pretesting of
      the soaking capacity of different net materials should be done at central level;
      the instructions for the impregnation procedures of different net materials
      (cotton and synthetic) should be simple and unambiguous; very cheap thin net
      materials should be avoided, particularly in the case of lambdacyhalothrin
      impregnation; educational methods and/or promotion of dark-colour nets should be
      further tested in order to decrease the washing frequency of bednets at household
      level; in areas with early-biting mosquitoes further studies on the protective
      efficacy of bednets are necessary; careful monitoring of side-effects,
      particularly those of last-generation pyrethroids, is necessary; and the
      community-based impregnation programme is a powerful tool for strengthening
      community involvement in health actions.

PMID- 9236829
TI  - The value of the polymerase chain reaction in the diagnosis of cutaneous T-cell
      infiltrates.
AB  - The distinction between reactive and neoplastic cutaneous T-cell infiltrates is
      difficult and requires good clinicopathologic correlation. Many cases manifest
      changes that are at the borderline between the two. The polymerase chain reaction
      (PCR) has been reported to detect monoclonality in 52-90% of cutaneous T-cell
      lymphomas and may be of use in the diagnosis of histologically borderline
      lesions. We have investigated the use of PCR in a series of borderline lesions
      including borderline biopsy samples from patients who subsequently developed
      cutaneous lymphoma. PCR amplification of T-cell receptor (TCR)-gamma chain gene
      was performed on formalin-fixed, paraffin-embedded tissue from 27 cases of
      clinically and histologically typical mycosis fungoides (MF), 22 borderline
      biopsy samples from 10 patients who subsequently developed MF (pre-MF), 32
      clinically suspicious, histologically borderline lesions, and 31 cases of chronic
      dermatitis. Monoclonality was demonstrated in 16 of 27 (59%) cases of MF, 10 of
      22 (50%) pre-MF biopsy samples (six of 10 patients), and six of 32 (19%)
      borderline biopsy samples. The same size monoclonal band was detected in pre-MF
      biopsy samples from six of seven patients in which a band was demonstrated in the
      diagnostic MF biopsy. Sequencing confirmed that the MF biopsy sample and the pre
      MF biopsy sample contained the same clone. The 31 dermatitis cases gave rise to
      polyclonal PCR products. Monoclonality can be demonstrated using PCR in 59% of MF
      cases, which is comparable with other T-cell lymphomas and in up to 50% of
      borderline biopsy samples in patients who later develop lymphoma. Detection of T
      cell monoclonality by PCR is strong evidence of an established or evolving
      cutaneous T-cell lymphoma.

PMID- 9236830
TI  - Thyroid paraganglioma: a clinicopathologic and immunohistochemical study of three
      cases.
AB  - We report three cases of intrathyroidal paraganglioma. The patients were adult
      women without significant personal or family histories that presented with an
      asymptomatic thyroid nodule. The tumors were single, well-circumscribed solid
      masses, 2 cm in greatest diameter, located within one thyroid lobe.
      Microscopically, they were encapsulated and showed the typical nesting
      (Zellballen) pattern of paraganglioma in other sites. Two of the tumors were
      composed of small- to medium-sized cells with granular amphophilic cytoplasm, and
      the third consisted of relatively large cells having a similar staining quality.
      Immunohistochemically, all tumors showed positivity for neuron-specific enolase,
      chromogranin A, and synaptophysin. S-100 protein-positive sustentacular cells
      were demonstrated in each case. Negative staining for epithelial markers,
      thyroglobulin, carcinoembryonic antigen, calcitonin, calcitonin gene-related
      peptide, serotonin, vimentin, and Congo red excluded other tumors that were
      considered in the differential diagnosis, such as medullary carcinoma,
      hyalinizing trabecular adenoma, atypical follicular adenoma, Hurthle-cell
      neoplasm, and metastatic carcinoid tumor. The patients were alive and well
      without evidence of recurrent disease at the time of the last follow-up. The
      previous literature on these tumors is discussed. We conclude that intrathyroidal
      paraganglioma exists and that this tumor can be distinguished from other similar
      appearing neoplasms in this organ.

PMID- 9236831
TI  - Metastatic neuroendocrine tumors to the thyroid gland mimicking medullary
      carcinoma: a pathologic and immunohistochemical study of six cases.
AB  - The clinical, pathological, and immunohistochemical features of six cases of
      metastatic neuroendocrine and carcinoid tumors to the thyroid simulating
      medullary thyroid carcinoma (MTC) are described. The patients were women between
      the ages of 24 and 70 years who, without symptoms or significant past medical
      histories, presented with either a single mass or multiple thyroid nodules. The
      primary source of the tumor was only discovered on follow-up. Two of the
      neoplasms were classical carcinoid tumors, one was a carcinoid predominantly
      composed of large cells, another showed a prominent oval to spindle cell
      component, and the two remaining cases were atypical carcinoid/high-grade
      neuroendocrine carcinomas. The immunohistochemical profile was inconsistent with
      MTC in that all tumors were negative for calcitonin and only two were focally
      positive for carcinoembryonic antigen (CEA). A variable pattern of staining for
      other neuroendocrine and epithelial markers was obtained in each case. Despite
      the morphologic and immunohistochemical similarities with MTC, the diagnosis of a
      metastatic neuroendocrine tumor to the thyroid should be favored in the presence
      of a predominantly interstitial pattern of spread; occurrence of multiple tumor
      foci; folliculotropism; rosette formations with lumen and cuticular borders; and
      lack of immunoreactivity for calcitonin and CEA. The differential diagnosis
      between MTC and metastatic neuroendocrine carcinoma to the thyroid is of
      importance because of the vast differences in treatment and prognosis.

PMID- 9236833
TI  - Lymph node involvement by splenic marginal zone lymphoma: morphological and
      immunohistochemical features.
AB  - Splenic marginal zone lymphoma (SMZL) has recently been proposed as a distinctive
      type of low-grade B-cell lymphoma. Although there is general agreement that this
      entity exists, its precise definition is blurred by uncertainty in differential
      diagnosis from other low-grade B-cell lymphomas. There is even more uncertainty
      as to the histology of splenic hilar and peripheral lymph nodes involved by SMZL.
      We therefore reviewed the histological and immunohistochemical features of 19 of
      these lymph nodes (14 hilar and five peripheral) from 14 cases of classical SMZL
      and compared them with the features of lymph nodes involved by other B-cell
      lymphomas. The morphology and immunohistology of the lymph nodes resemble those
      found in the white pulp of the spleen, showing a distinctive pattern, different
      from that which is observed in other B-cell lymphomas. In these cases, the
      overall architecture of the lymph nodes is effaced and replaced by a nodular
      infiltrate, although the sinuses are preserved in most hilar lymph nodes. Some of
      the nodules contain a central reactive follicular center, around which there is a
      broad zone of small lymphocytes. In other cases, the central area is partially
      infiltrated or, more commonly, totally replaced by these small lymphocytes, which
      in the periphery of the nodules showed a pale, slightly larger cytoplasm.
      Scattered nucleolated blasts are present, largely confined to the periphery of
      the nodules. The tumoral cells express immunoglobulin (Ig)D, IgM, and Ig light
      chain restriction and show a low proliferation fraction. These findings confirm
      that SMZL is a real entity, and not merely a morphological pattern of splenic
      infiltration by different types of low-grade B-cell lymphoma.

PMID- 9236832
TI  - Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases
      and review of the literature.
AB  - Composite pleomorphic xanthoastrocytoma (PXA)-ganglioglioma (GG) is a rare
      recently described entity. Only three examples have been documented, one of which
      showed evidence of malignant transformation. We report an additional four cases
      and update the literature. With the exception of an 82-year-old man, all patients
      have been under 30 years of age. The temporal lobe was involved in three cases
      and cerebellum in another three. Radiologic features were those common to PXA and
      GG. Histologically, all were "collision tumors" composed of abutting, although
      spatially distinct, PXA and GG components. In two cases, the second element was
      only recognized at reexcision or recurrence. Histologic anaplasia, always in the
      PXA component, was evident as brisk mitotic activity and/or necrosis in five
      cases. Of the seven patients, one died of disease 17 years after the onset of
      seizures and after multiple recurrences, the last of which largely resembled
      glioblastoma. We conclude that the composite PXA-GG is a rare neoplasm that
      shares many features of its individual components. In addition to its temporal
      lobe predilection, the cerebellum is frequently affected. As when it occurs in
      isolation, the PXA component of composite PXA-GG possesses the potential for
      malignant transformation.

PMID- 9236834
TI  - Hepatosplenic gamma/delta T-cell lymphoma: a report of two cases in
      immunocompromised patients, associated with isochromosome 7q.
AB  - Two cases of peripheral T-cell lymphoma, characterized by hepatosplenic
      presentation and gamma/delta T-cell receptor phenotype on malignant cells, are
      reported. Little is known about the chromosomal changes in these peculiar
      lymphomas. We report the cytogenetic analysis of these two patients.
      Isochromosome 7q and trisomy 8 were observed. These abnormalities were reported
      previously in five cases of gamma/delta T-cell lymphoma. These two patients had
      lymphomatous infiltration of the spleen, liver, bone marrow, and (in one case)
      lymph nodes. These abnormalities occurred in immunocompromised patients (i.e.,
      immunosuppressive therapy for kidney transplantation and chemotherapy for
      Hodgkin's disease), without Epstein-Barr virus infection stigmata in tumor cells.

PMID- 9236835
TI  - Immunophenotyping of dermal spindle cell tumors: diagnostic value of monocyte
      marker Ki-M1p and histogenetic considerations.
AB  - Various studies have reported the utility of anti-CD34 staining in the
      differential diagnosis of dermal spindle-cell tumors. To investigate whether
      monoclonal antibody Ki-M1p might add practical diagnostic information, we
      examined a total of 120 cutaneous spindle cell neoplasms using a panel of
      markers. Anti-CD34 antibody QBEnd/10 consistently stained dermatofibrosarcomas,
      Kaposi's sarcomas, neurofibromas, and, to a lesser extent, hemangiopericytomas. A
      positive reaction was also found in > 18% of the dermatofibromas. Ki-M1p staining
      showed an intense immunoreaction in all dermatofibromas, whereas no reactivity
      was observed in dermatofibrosarcomas. In addition, a subset of cells was labeled
      in atypical fibroxanthomas and Kaposi's sarcomas. Neurofibromas, spindle-cell
      hemangioendotheliomas, and hemangiopericytomas were negative.
      Dermatofibrosarcomas and atypical fibroxanthomas also moderately expressed smooth
      muscle-specific actin. Immunohistochemically, a discrimination between
      dermatofibrosarcomas and neurofibromas was possible only by means of an antibody
      against the nerve growth factor receptor. We conclude that the combination of
      several antibodies, in particular anti-CD34 and Ki-M1p, may improve the accuracy
      of diagnostic immunohistochemistry in the field of cutaneous spindle cell tumors.
      We speculate that dermatofibroma is primarily a macrophage-rich inflammatory
      lesion in which cytokine secretion induces a secondary proliferation of
      fibroblasts, whereas dermatofibrosarcoma is likely to issue from primitive dermal
      cells of uncertain origin.

PMID- 9236836
TI  - p53 and K-ras mutational genotyping in pulmonary carcinosarcoma, spindle cell
      carcinoma, and pulmonary blastoma: implications for histogenesis.
AB  - In an attempt to understand the molecular pathogenesis of biphasic pulmonary
      neoplasms, the authors studied 25 cases of carcinosarcoma, spindle cell
      carcinoma, and pulmonary blastoma using a combined immunohistochemical and
      topographic genotyping approach for the presence of p53 abnormalities within the
      different epithelial and mesenchymal components of these tumors. Genotyping
      involved a search for point mutational damage in p53 exons 5-8, which was
      correlated with p53 immunoreactivity. This analytical approach demonstrated p53
      missense point mutations in four of nine cases of spindle cell carcinoma with a
      100% concordance rate between p53 immunopositivity and the presence of DNA
      mutational damage. One of six carcinosarcomas, heterologous in type, exhibited a
      p53 mutation. The concordance rate among carcinosarcomas was also 100%. However,
      the concordance rate among classic biphasic pulmonary blastomas was only 43%,
      with one of seven cases demonstrating a p53 mutation by DNA genotyping. The lack
      of concordance in pulmonary blastomas was possibly due to the existence of
      genotypically distinct subsets of tumor cells likely bearing mutations among
      largely nonmutated cells. In a similar fashion, among three well-differentiated
      fetal type adenocarcinomas, no p53 mutations were detected despite the presence
      of focal p53 immunopositivity in one of the cases. No K-ras mutations were
      detected in any of the 25 tumors examined. Monoclonal histogenesis from a single
      totipotential cell in a subset of these neoplasms (six of 22 cases) was supported
      by the finding of p53 overexpression and identical p53 mutational genotype in
      both the epithelial and spindle elements of the tumors. Furthermore, the finding
      of a small percentage of p53-positive tumor cells within one or both components
      suggests late acquisition of p53 mutational change in a subset of pulmonary
      blastomas.

PMID- 9236837
TI  - Diagnostic accuracy of a rural live video telepathology system.
AB  - Accuracy of diagnoses rendered using a live video telepathology network was
      assessed for permanent sections of surgical pathology specimens. To determine
      accuracy, telepathology diagnoses were compared with those obtained by directly
      viewing the glass slide using a standard microscope. A total of 294 cases were
      read via both telepathology and glass slide by attending pathologists at a
      tertiary care medical center. Overall accuracy was defined as exact concordance
      between diagnoses. Clinically insignificant differences in diagnoses were
      excluded to determine clinically significant accuracy. For the 285 cases with
      complete data, the overall accuracy for telepathology was 0.912 (95% confidence
      interval [CI], 0.872-0.941), whereas the overall accuracy for glass slide
      readings was 0.968 (95% CI, 0.939-0.985). This difference is statistically
      significant (p = 0.009). When focusing on clinically significant discrepancies,
      where the difference in diagnosis might affect therapeutic decisions, the video
      accuracy was only slightly less than the glass slide accuracy (0.965 [95% CI,
      0.934-0.982] vs. 0.982 [95% CI, 0.957-0.994], respectively), but this difference
      is not statistically significant (p = 0.302). Most of the cases with clinically
      significant differences involved lesions with inherently high interobserver
      variation. Certainty of diagnosis did not differ between video and glass slide
      readings (p = 0.911), but there was an association between certainty of diagnosis
      and diagnostic accuracy for video (p = 0.003 for clinically significant
      accuracies). Based on these findings, we recommend when using this telepathology
      system that only preliminary diagnoses should be given in the following
      situations: for diagnostic areas with known high interobserver variability; when
      the consultant has any degree of uncertainty about the presence or absence of the
      lesion in question; and when there is insufficient experience using telepathology
      as a diagnostic medium.

PMID- 9236838
TI  - Clear cell ependymoma: a mimic of oligodendroglioma: clinicopathologic and
      ultrastructural considerations.
AB  - Although clear cells resembling oligodendrocytes are known to occur in
      ependymomas, tumors composed primarily of such cells, i.e., clear cell ependymoma
      (CCE), are rare. Herein we characterize the clinicopathologic features of eight
      examples of CCE encountered at Mayo Clinic from 1983 to 1996. The tumors occurred
      in patients 3-31 years of age and presented as well-demarcated, deeply situated,
      contrast-enhancing masses, all of which were supratentorial. All but one case
      lacked classic light microscopic features of ependymoma. Although nearly all were
      immunoreactive for glial fibrillary acidic protein, it was electron microscopy
      that showed the diagnostic hallmarks of ependymoma, including complex
      intercellular junctions, surface microvilli and cilia, and microrosette
      formation, thus underscoring the importance of electron microscopy in the
      diagnosis of clear cell ependymomas. The differential diagnosis of CCE includes
      not only oligodendroglioma, but central neurocytoma and glioneurocytoma. Unlike
      oligodendrogliomas, CCEs are characterized by their sharp circumscription,
      hypervascularity as reflected in contrast enhancement on computed tomography and
      magnetic resonance imaging, their noninfiltrative pattern of growth that
      displaces parenchyma, and the occasional formation of vague perivascular
      pseudorosettes. Unlike central neurocytomas and glioneurocytomas, CCE lack
      secretory granules, vesicles, and synapses by electron microscopy and
      neuroendocrine markers by immunocytochemistry. In summary, the diagnosis of CCE
      requires neuroimaging, histologic, and ultrastructural correlation. The latter is
      essential in a limited biopsy. Ultrastructural studies also play a role in
      identifying glioneurocytomas. CCEs behave like more ordinary ependymomas. The
      importance of their recognition is the avoidance of alternative diagnoses and
      inappropriate therapies.

PMID- 9236839
TI  - Splenic vascular tumors: a histologic, immunophenotypic, and virologic study.
AB  - Vascular tumors of the spleen include several different entities, some of which
      are unique to that organ. Twenty-two such proliferations were studied, including
      10 hemangiomas, six littoral cell angiomas, four angiosarcomas, and two
      hamartomas. The hemangiomas included seven with localized tumors and three with
      diffuse angiomatosis of the spleen. All cases were studied by paraffin section
      immunohistochemistry with a large panel of antibodies. In addition, all cases
      were studied for the presence of the Kaposi's sarcoma-associated herpesvirus
      (KSHV) using the polymerase chain reaction. The morphologic findings were similar
      to those previously reported. All proliferations were vimentin positive, and one
      angiosarcoma was focally keratin positive. All cases reacted for CD31, whereas 20
      of 22 were positive for von Willebrand's factor and 19 of 22 were positive for
      Ulex europeaus. CD34 expression in lining cells was identified in 10 of 10
      hemangiomas, two of four angiosarcomas, and one of two hamartomas, whereas all
      six cases of littoral cell angioma were negative. CD68 was expressed in all cases
      of littoral cell angioma but was also positive in all three diffuse hemangiomas,
      two of seven localized hemangiomas, and two of four angiosarcomas. CD21
      expression was restricted to the lining cells of littoral cell angioma, and CD8
      expression was only identified in two of two hamartomas and two of four
      angiosarcomas. KSHV was not detected in any of the cases. These findings suggest
      that there are distinct immunophenotypic as well as morphologic features of
      splenic vascular tumors. Littoral cell angiomas have a characteristic CD34
      /CD68+/CD21+/CD8- immunophenotype and hamartomas have a characteristic CD68-/CD21
      /CD8+ phenotype. The frequent CD68 expression in diffuse hemangioma suggests an
      immunophenotypic difference from localized hemangioma of the spleen.

PMID- 9236840
TI  - Nuchal fibrocartilaginous pseudotumor: a distinctive soft-tissue lesion
      associated with prior neck injury.
AB  - Soft-tissue tumors with a predilection to involve the head and neck region
      include spindle cell lipoma, pleomorphic lipoma, and nuchal fibroma. We have
      recently studied three patients with distinctive soft-tissue fibrocartilaginous
      masses in the posterior aspect of the base of the neck, at the junction of the
      nuchal ligament and the deep cervical fascia. Two of the patients were women
      (ages 37 and 40) and one a man (age 53). All three had sustained neck injuries in
      automobile accidents in the past (27 years, 20 years, and 2 months before
      surgery, respectively). Each patient presented with a soft-tissue nodule
      overlying the spinous process of one of the lower cervical vertebrae. Two were
      painful. Computed tomography and magnetic resonance imaging performed in two
      patients showed focal thickening of the ligamentum nuchae at the C4-5 and C5-6
      levels. All three masses were completely excised. They ranged in size from 1.0 to
      1.5 cm. The three lesions were histologically identical, and each consisted of a
      poorly defined, moderately cellular fibrocartilage nodule located within the
      nuchal ligament at its junction with the deep cervical fascia. Atypia or mitotic
      activity was not present. The ligamentous tissue adjacent to the mass was
      irregular and degenerated. None of the masses have recurred in follow-up periods
      of 3 to 6 months, and all patients are currently asymptomatic. The lesion we
      describe is a distinctive soft-tissue pseudotumor that occurs in the mid-line of
      the lower cervical spine within the nuchal ligament. It is likely non-neoplastic
      and probably develops as a reaction to soft-tissue injury, in an analogous manner
      to fibrocartilage metaplasia seen in degenerated tendoligamentous structures. We
      propose the term "nuchal fibrocartilaginous pseudotumor" for these lesions.

PMID- 9236841
TI  - Membranous fat necrosis in lipomas.
AB  - Membranous fat necrosis (MFN) is an under-recognized variant of fat necrosis (FN)
      that is characterized by the presence of membranocystic foci in which cysts are
      lined by an eosinophilic, homogeneous membrane with pseudo-papillary luminal
      projections. Although MFN has been described in systemic adipose tissue, it has
      not been described in lipomas. We report the rare occurrence of MFN in four
      lipomas. The lipomas ranged in size between 9 and 22 cm and occurred in
      menopausal women in the left shoulder, right upper back, right thigh, and gluteal
      regions. In two cases the membranocystic foci were identified macroscopically,
      whereas in the other two cases MFN was only identified on histologic assessment.
      Apart from the typical histologic appearance of the membranocystic foci, the
      membranes have a distinct histochemical profile that includes consistent Sudan
      black positivity and either periodic acid-Schiff or Ziehl-Neelsen positivity. In
      all cases, there was autofluorescence of the membranes on immunofluorescent
      examination of unstained sections. These membranocystic foci have the typical
      staining reactions of ceroid pigment. The exact cause of MFN in lipomas is not
      known, but in view of their large sizes, traumatic and ischemic etiologies are
      proposed.

PMID- 9236842
TI  - Herpesvirus 6 variant A infection after heart transplantation with giant cell
      transformation in bile ductular and gastroduodenal epithelium.
AB  - Herpesvirus 6 (HHV-6) is a ubiquitous virus known to cause febrile syndromes and
      exanthema subitum in children. Less commonly, and particularly in organ
      transplant recipients, it may result in hepatitis, bone marrow suppression,
      interstitial pneunonitis, and meningoencephalitis. This report expands the
      spectrum of clinical disease associated with HHV-6 by documenting viral infection
      in a 44-year-old heart transplant recipient presenting with gastroduodenitis,
      pancreatitis, and hepatitis. On histopathologic examination, the gastric,
      duodenal, and bile ductular epithelium showed a multinucleate giant cell
      transformation similar to the cytopathic effect caused by the virus in human T
      lymphocytes infected in vitro. Electron microscopy showed herpes particles with a
      thick tegument layer in the duodenum. Polymerase chain reaction amplified HHV-6
      variant A sequences from multiple sites. Serology confirmed the presence of an
      acute HHV-6 infection. Thus, HHV-6 variant A can cause gastroduodenitis and
      pancreatitis in immunosuppressed individuals. Multinucleate giant cells and
      enveloped virions with a prominent tegument can be used as morphologic criteria
      to raise the possibility of HHV-6 infection in human biopsy tissue.

PMID- 9236843
TI  - Pleuropulmonary blastoma: fluorescence in situ hybridization analysis indicating
      trisomy 2.
AB  - We report a case of pleuropulmonary blastoma occurring in the right upper lobe
      and pleura of a 29-month-old boy. Histologically, the tumor was composed of
      undifferentiated mesenchymal cells with occasional rhabdomyoblastic and chondroid
      differentiation. Immunohistochemical analysis showed vimentin immunoreactivity in
      most of the tumor cells, myoglobin, desmin, and actin in the rhabdoid cells, and
      S-100 protein in the chondroid cells. Fluorescence in situ hybridization (FISH)
      analysis showed trisomy 2 and normal chromosomal copy numbers for chromosomes 7,
      12, 17, 18, and X in the majority of the tumor cell nuclei. The identification of
      trisomy 2 in the current pleuropulmonary blastoma confirms a previous cytogenetic
      finding of chromosome 2 abnormality with cultured metaphase cells of a similar
      case, indicating that the acquisition of an additional chromosome 2 copy in
      pleuropulmonary blastoma is a nonrandom chromosomal alteration and that
      pleuropulmonary blastoma is cytogenetically distinct from pulmonary blastoma in
      which chromosome 2 is bisomic. It is also suggested that pleuropulmonary blastoma
      may have an intimate tumorigenetic relationship with embryonal rhabdomyosarcoma.

PMID- 9236845
TI  - Creating low-power photomicrographs using a 35 mm digital slide scanner.
AB  - A method for obtaining high quality photomicrographs at very low power
      magnification using a digital slide scanner is described. Using an easily
      modified 35-mm film slide mount, it is possible to scan a conventional 25-mm wide
      glass slide and to obtain an image that is uniformly in focus and of even
      illumination. The computer bitmap file that is generated is suitable for computer
      presentations or publication-quality prints and may be magnified up to 12-fold
      without significant image degradation.

PMID- 9236844
TI  - Intravascular large cell lymphoma coexisting within hemangiomas of the skin.
AB  - Intravascular lymphomatosis is a rare and peculiar subtype of large cell
      lymphoma. The authors present the pathologic, clinical, and radiologic findings
      of a patient with intravascular large cell lymphoma coexisting within hemangiomas
      of the skin. Initially the lymphoma was clinically confined to the hemangiomas
      and the patient was closely observed for disease progression. Within 10 months
      the patient developed disseminated lymphoma involving both adrenals. A clinical
      remission was achieved, but the patient soon relapsed, and despite further
      chemotherapy he died with disseminated disease 23 months after the initial
      diagnosis. This report presents the only known case of an intravascular large
      cell lymphoma coexisting within a vascular lesion and highlights the potential
      aggressive nature of intravascular lymphomas.

PMID- 9236846
TI  - Expression of p53 and CEA in atypical adenomatous hyperplasia of the lung.

PMID- 9236847
TI  - Visualization of injected embolic material.

PMID- 9236848
TI  - Oligonucleotide analogs might be designed to bind to m-RNA.

PMID- 9236849
TI  - Antisense oligonucleotide inhibitors of isozymes of protein kinase C: in vitro
      and in vivo activity, and clinical development as anti-cancer therapeutics.

PMID- 9236850
TI  - First- and second-generation antisense inhibitors targeted to human c-raf kinase:
      in vitro and in vivo studies.

PMID- 9236851
TI  - Developing oligonucleotide therapeutics for human leukemia.

PMID- 9236852
TI  - In vitro and in vivo activity of antisense inhibitors of ras: potential for
      clinical development.

PMID- 9236853
TI  - Targeting c-myc in leukemia.

PMID- 9236854
TI  - Antisense oligonucleotide inhibitors for the treatment of cancer: 1.
      Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides.

PMID- 9236855
TI  - Antisense oligonucleotide inhibitors for the treatment of cancer: 2.
      Toxicological properties of phosphorothioate oligodeoxynucleotides.

PMID- 9236856
TI  - Toxicological and pharmacokinetic properties of chemically modified antisense
      oligonucleotide inhibitors of PKC-alpha and C-raf kinase.

PMID- 9236857
TI  - Immune stimulation--a class effect of phosphorothioate oligodeoxynucleotides in
      rodents.
AB  - Treatment of rodents with phosphorothioate oligodeoxynucleotides induces a form
      of immune stimulation characterized by splenomegaly, lymphoid hyperplasia,
      hypergammaglobulinemia and mixed mononuclear cellular infiltrates in numerous
      tissues. Immune stimulation was evaluated in mice with in vivo and in vitro
      studies using a review of historical data and specific in vivo and in vitro
      studies. All phosphorothioate oligodeoxynucleotides evaluated induced
      splenomegaly and B-lymphocyte proliferation. Splenomegaly and B-lymphocyte
      proliferation increased with dose or concentration of oligodeoxynucleotide.
      Splenomegaly appeared to occur, at least in part, as a result of stimulation of B
      lymphocyte proliferation. There were differences with respect to degree or
      potency of immune stimulation by different oligodeoxynucleotides. The rank order
      potencies for B-lymphocyte proliferation in vitro and splenomegaly correlated
      well for the oligodeoxynucleotides tested. Particular oligodeoxynucleotide
      sequence motifs or palindromes have been demonstrated to affect in vitro cell
      proliferation. Inclusion of a 5'-AACGTT-3' palindrome in a phosphorothioate
      oligodeoxynucleotide sequence significantly enhanced the potency. While inclusion
      of this palindrome or a CpG motif alone may contribute to the immune stimulation,
      these palindromes and motifs were clearly not the sole factor required for immune
      stimulation. Several phosphorothioate oligodeoxynucleotides that did not contain
      a CpG motif still induced immune stimulation in mice. The immune stimulation
      induced by phosphorothioate oligodeoxynucleotides was an effect of this class of
      compounds to which rodents are acutely sensitive.

PMID- 9236858
TI  - Recent developments in triple-helix regulation of gene expression.

PMID- 9236859
TI  - Angiogenesis: new aspects relating to its initiation and control.
AB  - Angiogenesis, the formation of new microvessels from parent microvessels,
      involves remodeling the basement membrane and interstitial extracellular matrix
      (ECM) using degrading proteases produced by the endothelial cells (ECs) and other
      adjacent cells, and the synthesis of ECM molecules by these cells. Degraded ECM
      releases previously bound heparin-binding cytokines (and growth factors) which
      are able to act as ligands to high-affinity receptors on various target cells,
      including ECs. The EC carries receptors for a number of cytokines which are
      produced by neighboring cells or released from the ECM and which can either
      induce or suppress the angiogenic phenotype of the EC. ECs are able to synthesize
      and secrete cytokines with auto- and paracrine effects. Angiogenesis, which
      virtually never occurs physiologically in adult tissues (except in the ovary, the
      endometrium and the placenta), is essential in wound healing and inflammation.
      Angiogenesis is, in fact, strictly controlled by a redundancy of pro- and anti
      angiogenic paracrine peptide molecules, some of which have recently been
      described. The expression and synthesis of two distinct anti-angiogenic factors
      is, for example, controlled by the p53 tumor suppressor gene. In certain hypoxic
      conditions, chronic inflammatory diseases and syndromes, angiogenesis is of
      pathogenic and prognostic significance. Angiogenesis is, moreover, essential for
      the growth and metastatic spread of solid tumors. This indicates the potential
      for developing new therapeutic strategies not only for tumors but also in
      diseases such as rheumatoid arthritis, psoriasis, liver cirrhosis and diabetic
      retinopathy. Moreover, the therapeutic induction of angiogenesis in ischemic
      tissues using recombinant cytokines is also promising for clinical application.
      In fact, the first successful human gene therapy for stimulating angiogenesis has
      recently been reported.

PMID- 9236860
TI  - Ginseng treatment enhances bacterial clearance and decreases lung pathology in
      athymic rats with chronic P. aeruginosa pneumonia.
AB  - In an athymic rat model of chronic Pseudomonas aeruginosa lung infection
      mimicking cystic fibrosis (CF), we studied the effects of the Chinese herb
      ginseng. Rats were treated subcutaneously with ginseng extracts (25 mg/kg) once a
      day for 10 days after challenge with P. aeruginosa embedded in alginate beads. We
      found that ginseng treatment significantly reduced bacterial load (p < 0.02) and
      the number of mast cells in the lungs (p < 0.01). Furthermore, it decreased the
      severity of lung pathology (p < 0.02) and lowered serum anti-P. aeruginosa IgM
      and IgA antibody levels (p < 0.004, p < 0.04) compared to the control group. The
      down-regulated specific humoral immunity in the ginseng-treated group and the
      fact that athymic rats have a severely compromised T-cell-mediated immune
      reactivity due to the absence of thymus might suggest an activation of innate
      immunity after ginseng treatment. Our findings indicate that ginseng treatment
      increases the resistance of the athymic rats to P. aeruginosa lung infection. We
      therefore think that ginseng has promising potential as a natural medicine for
      stimulation of the immune system in CF patients with chronic P. aeruginosa lung
      infections.

PMID- 9236861
TI  - Primary T-cell lymphoma of the breast with lymphoepithelial lesion. A case
      report.
AB  - Fine-needle aspiration, histomorphologic and immunologic findings in a case of
      primary T-cell lymphoma of the breast are reported. The tumor cells were
      diagnosed as large cell lymphoma with lymphoepithelial lesion and no nuclear
      multilobulation. No serologic evidence of HTLV-1 infection was detected. After
      simple mastectomy, lymph node dissection and chemotherapy, the patient is now
      doing well, having been followed for 30 months. To our knowledge, this is the
      first case report of primary T-cell lymphoma of the breast with prominent
      lymphoepithelial lesion, no nuclear lobularity, and an indolent clinical course.

PMID- 9236863
TI  - Eikenella corrodens-caused botryomycosis-type pneumonia in a barbary ape (Macaca
      sylvanus).
AB  - An 18-year-old female barbary ape in a safari park died from a mixed bacterial
      infection. Staphylococus aureus was isolated from a purulent necrotic mastitis
      and from a chronic purulent granulomatous sialoadenitis of the sublingual glands,
      Eikenella corrodens from a botryomycosis-type pneumonia. As judged by
      histopathology, mixed infection of S. aureus and E. corrodens was present in the
      sialoadenitis, and E. corrodens botryomycosis-type bacterial colonies were also
      present in the pancreatic parenchyma, though here no bacteriological isolation
      was attempted. A generalized amyloidosis, and especially pancreatic islet
      amyloidosis, probably indicated an altered immunological competence.

PMID- 9236862
TI  - The clonal antibody response to Pseudomonas aeruginosa heat shock protein is
      highly diverse in cystic fibrosis patients.
AB  - The GroEL protein of Pseudomonas aeruginosa belongs to the bacterial 60-65 kDa
      heat shock protein family. A strong antibody response to GroEL has been found in
      cystic fibrosis (CF) patients with chronic pulmonary infection caused by P.
      aeruginosa. Clonotypes of IgG1 and IgG2 antibodies against GroEL were studied in
      60 consecutive sera from 18 CF patients with chronic P. aeruginosa infection
      using isoelectric focusing in combination with affinity immunoblotting. The
      persistent antigenic stimulation in CF patients with chronic P. aeruginosa
      infection induced numerous IgG1 and particularly IgG2 antibody clones against
      GroEL. The appearance of new clones with time reflected the long duration of the
      chronic infection. A striking addition of new clonotypes during the observation
      period occurred when a new unrelated bacterium (Burkholderia cepacia) had become
      established as a cause of the pulmonary infection, or when the P. aeruginosa
      infection became chronic.

PMID- 9236864
TI  - Congenital heart block: HLA differences between affected children and healthy
      siblings in four Finnish families.
AB  - Congenital heart block without intracardiac anatomic malformations is a
      potentially lethal disease affecting children and newborns. The mother often has
      an autoimmune disorder with autoantibodies against SS-A/Ro and/or SS-B/La
      antigens. However, only a minority of the children of these mothers develop
      complete heart block. It is believed that the maternal antibodies are pathogenic,
      but other immunological mechanisms such as cell-mediated injury cannot be
      excluded. Maternal cells may recognize fetal antigens adjacent to fetal HLA, and
      thus some children may be more susceptible to heart block than others, depending
      on their HLA genetics. The purpose of this study was to evaluate whether there
      are HLA differences between children with heart block and their healthy siblings.
      Six affected children in four families and their siblings were studied. MHC class
      I were typed serologically and class II and some non-HLA alleles were typed by
      DNA techniques. DQB1*03/04 were seen more often in the affected children than in
      the siblings. Some other differences were also seen in the other antigens of the
      MHC area.

PMID- 9236866
TI  - Primary retroperitoneal mucinous tumor of low malignant potential: histogenetic
      aspects and review of the literature.
AB  - We report an unusual mucinous tumor of low malignant potential, of ovarian-like
      type, arising in the retroperitoneum of an otherwise healthy 33-year-old woman.
      This is the fifth described case of such a tumor in the world literature, and the
      first reported in Scandinavia or Europe. We also discuss aspects of the
      histogenesis of this type of tumor and review the available literature. The
      histological heterogeneity and metastatic potential of the tumor warrant careful
      histopathologic analysis and follow-up of patients presenting with such lesions.

PMID- 9236865
TI  - High-molecular weight IGF-2 expression in a haemangiopericytoma associated with
      hypoglycaemia.
AB  - Spontaneous hypoglycaemia is usually caused by an insulin-producing islet-cell
      tumour of the pancreas. Rarely, it can be caused by non-islet cell tumours. Most
      of the tumours are of mesenchymal type, large, and slowly growing. One
      representative is haemangiopericytoma (HAP). The present report describes a case
      of a large recurrent retroperitoneal HAP associated with severe hypoglycaemia.
      Blood serum insulin and proinsulin concentrations were low. By means of acid-gel
      chromatography and dot-blot techniques, an increased amount of a high-molecular
      weight IGF-2 peptide was found. By using antigen retrieval procedures, IGF-2
      immunoreactive tumour cells were found in specimens of the recent tumour
      recurrence-but not in the original. When the in situ hybridization technique was
      used it could be shown that IGF-2 mRNA labelling had already occurred in the
      original tumour specimen, 11 years before the onset of hypoglycaemic symptoms.
      These observations confirm the hypothesized hypoglycaemic effects of high
      molecular-weight (HMW) IGF-2, but also point to the presence of a prolonged
      compensation of this effect. A literature review, based on 17 similar cases of
      haemangiopericytoma with hypoglycaemia, is presented. Our observation and
      findings in the literature review support the idea that non-islet-cell tumour
      hypoglycaemia is caused by an overproduction of a HMW IGF-2 peptide. The insulin
      like effect is mediated via non-specific binding to the insulin receptors. To
      anticipate patients at risk of developing this kind of hypoglycaemia, the
      histopathological investigation should include not only immunohistochemical
      analyses of the presence of IGF-2 peptide, but also in situ hybridization of the
      IGF-2 mRNA expression.

PMID- 9236867
TI  - Tumor growth in a defined microcirculation.
AB  - The fate of human tumor cells deposited in rat uteri was investigated by light
      microscopy of histological sections, immunohistochemistry, and scanning electron
      microscopy of microvascular corrosion casts. The human colonic tumor cell line LS
      174 T was used as graft since it can be detected by CEA immunohistochemistry, and
      spayed nude rats (PVG rnu/rnu) were used as hosts, subjected to different
      hormonal regimens (no exogenous hormones, medroxyprogesterone acetate, 17-beta
      estradiol, or the last two regimens in combination). Intrauterine deposition of a
      suspension of 2 x 10(6) tumor cells resulted in tumor take in 72% (21/29) of the
      nude rats. Endometrial growth was verified in only three animals (14%, 3/21).
      Extraendometrial growth, however, was found in all animals with tumor take. These
      observations suggest that the endometrium is comparatively resistant to growth of
      xenografted human colonic tumor cells. The tumor microcirculation consisted of
      new vessels, giving morphological evidence that tumor growth is dependent on
      angiogenesis and not on invasion of preexisting vessels.

PMID- 9236868
TI  - Clinical-basic science connection.

PMID- 9236869
TI  - The short- and long-term side effects of carbon dioxide laser resurfacing.
AB  - BACKGROUND: Carbon dioxide (CO2) laser resurfacing has become a very popular
      method of rhytide and scar removal in the recent past. Preliminary studies have
      been published describing the method, histology, and clinical results of CO2
      laser resurfacing. However, none of these studies has dealt with long-term follow
      up results. OBJECTIVE: To review all side effects resulting from CO2 laser
      resurfacing with regard to both short- and long-term effects. METHOD:
      Retrospective analysis of 104 patients who have undergone CO2 laser resurfacing
      for either facial rhytides and/or scarring with follow-up periods of 4-23 months
      (average, 8.2 months). RESULTS: The incidence of side effects are generally very
      low for CO2 laser resurfacing, including scarring, postinflammatory
      hyperpigmentation, and infection. However, there is a significant and previously
      unreported risk of hypopigmentation in an area of the population who often seek
      improvement in the appearance. CONCLUSIONS: CO2 laser resurfacing of facial
      rhytides and acne scars can be a very safe procedure by an experienced laser
      operator. However, careful patient selection, thorough patient instruction, and
      proper aesthetic analysis of treatment sites must be followed to insure the most
      favorable outcomes with CO2 laser resurfacing.

PMID- 9236870
TI  - Infections complicating pulsed carbon dioxide laser resurfacing for photoaged
      facial skin.
AB  - BACKGROUND: With proper technique and instrumentation, laser resurfacing for
      facial wrinkles has been found to be highly effective and relatively safe. Most,
      if not all, of the noninfectious complications such as pigmentary changes,
      scarring, and persistent erythema can either be avoided or managed with
      appropriate therapy. Postoperative infections, on the other hand, may develop
      despite proper technique and instrumentation. Without proper management, they may
      cause significant physical morbidity and psychological distress defying the
      expected benefit of the procedure. OBJECTIVE: To quantify the incidence and to
      study the characteristics of infections arising after laser resurfacing for
      facial wrinkles with pulsed carbon dioxide laser treatment. METHOD: A
      retrospective study was carried out by reviewing the records of all patients
      undergoing laser resurfacing for facial wrinkles from January 1, 1995 to April
      30, 1996. An infection is defined as a positive culture in the presence of signs
      or symptoms of an infection. RESULTS: Over 16 months, 395 procedures were
      performed and 17 cases of culture-proven infection recorded, an incidence of
      4.3%. All patients had symptoms starting between days 2 and 10 after the
      operation. Over half of the patients had multiple infections with two to three
      microorganisms. Pseudomonas aeruginosa was the most common causative agent, found
      in 41% of all infected cases, followed by Staphylococcus aureus (35%), S.
      epidermidis (35%), and Candida species (24%). Multiple drug-resistant, gram
      negative bacteria were found in four cases, implicating the possibility of
      hospital-acquired infections. Almost all isolates of gram-positive bacteria were
      resistant to both erythromycin and penicillin, but not oxacillin. With proper
      treatment, most patients healed normally. Only one patient had persistent,
      multiple atrophic scars due to locally disseminated herpes simplex infection
      despite proper prophylaxis and treatment. CONCLUSIONS: Postoperative infection is
      uncommon and manageable with early recognition and proper treatment. The types of
      infectious agents being found are very similar to those reported in burn
      patients. This complication has been found to be much more common in patients
      undergoing full face resurfacing and those using a bio-occlusive dressing
      postoperatively. With comprehensive preventive and management measures, it is
      likely that this type of uncommon, yet distressful, complication can be avoided
      and more successfully treated. Recommendations are made for prevention and
      management of suspected postoperative infections.

PMID- 9236871
TI  - A surgical wound infection due to Mycobacterium chelonae successfully treated
      with clarithromycin.
AB  - BACKGROUND: Mycobacterium chelonae is an uncommon but recognized cause of chronic
      localized cutaneous infection at a site of penetrating trauma or a surgical
      wound. OBJECTIVE: The problem faced by physicians encountering an infection by M.
      chelonae is often response to therapy, which may be highly variable. METHODS: We
      describe an immunocompetent patient who developed a localized infection due to M.
      chelonae following surgery for a basal cell carcinoma of the lower leg. RESULTS:
      The infection responded to treatment with clarithromycin. CONCLUSION: The
      clinical efficacy of clarithromycin and the salient features of M. chelonae
      infection and its treatment are discussed.

PMID- 9236872
TI  - Dog ear: true and false. A simple surgical management.
AB  - The rise of the utilization of tissue expanders and procedures like liposuction
      have brought us a better understanding of the biomechanical properties of the
      skin as a living organ. This understanding has helped us to appreciate better the
      etiopathology of a dog ear deformity and to utilize the same properties for its
      correction by simple methods and thus avoid complex plasties and additional
      scars.

PMID- 9236873
TI  - Cutaneous micrographic surgery for atypical fibroxanthoma.
AB  - BACKGROUND: Atypical fibroxanthoma is a locally aggressive cutaneous tumor of the
      head and neck. Reported treatments include simple excision, cryosurgery,
      radiation, and cutaneous micrographic surgery. OBJECTIVE: We wish to further
      document the use of cutaneous micrographic surgery for local control of atypical
      fibroxanthoma. METHODS: A retrospective study of six cases from the University of
      Missouri-Columbia and a review of the literature. RESULTS: Five (84%) of our
      cases were on the heads of elderly patients with strong evidence of photodamage.
      Subclinical extension of atypical fibroxanthoma required surgical margins
      averaging 9 mm. Cutaneous micrographic surgery has been associated with no
      recurrences. CONCLUSION: The results of our data demonstrate cutaneous
      micrographic surgery to be an excellent modality to address this locally
      aggressive tumor. Cutaneous micrographic surgery is an advantageous therapy for
      this tumor because of its meticulous tissue removal, tissue mapping, and tissue
      sparing qualities.

PMID- 9236874
TI  - The development of a Marjolin's cancer in a human immunodeficiency virus-positive
      hemophilic man and review of the literature.
AB  - BACKGROUND: The malignant potential of chronic ulcers and scars secondary to a
      variety of injuries is well characterized in the medical literature. Furthermore,
      it has been reported that human immunodeficiency virus (HIV)-positive patients
      have a higher incidence of basal cell carcinoma (BCC) than the general
      population. OBJECTIVE: To describe a case of an unusually aggressive morpheaform
      BCC that developed in a 28-year-old HIV-positive patient. The tumor developed in
      a scar 25 years after the initial trauma (Marjolin's ulcer). METHODS: Description
      of a case and review of the literature of Marjolins ulcer. RESULTS: The tumor was
      removed in a seven-stage, 21-section, micrographically controlled excision.
      Intraoperatively, perineural invasion of the infraorbital nerve was observed. The
      postoperative defect was repaired using a full-thickness skin graft. CONCLUSION:
      Although most malignancies arising within chronic scars are SCCs, BCCs and a
      number of other tumors have been described. Mohs micrographic surgery was
      effective in treating this aggressive morpheaform BCC. A high degree of suspicion
      in any changing healed scar is recommended.

PMID- 9236875
TI  - Malignant tumors of the orbital region. Analysis of cases examined from 1986 to
      1995.
AB  - OBJECTIVE: To present a retrospective study of 154 orbital tumors examined from
      1986 to 1995. METHODS: We analyzed the clinical behavior and the degree of local
      malignity also in relationship with the particular anatomical characteristics of
      this site. RESULTS: In this are, it is not rare finding tumors with a scarce
      cutaneous extension but a deep involvement including the bone, or of recurrences
      after a previous insufficient treatment with an aggressive clinical course.
      CONCLUSION: The principles for the surgical approach are: exeresis as radical as
      possible, one-stage operation for tumoral resection and reconstruction, bringing
      of trophic tissue able to sustain any complementary treatment, easy and fast
      execution, and short clinical course.

PMID- 9236876
TI  - Treatment of vulvar varicosities by injection-compression sclerotherapy.
AB  - BACKGROUND: Techniques of injection-compression sclerotherapy of lower extremity
      varicosities can be applied to treat patients with symptomatic vulvar
      varicosities. OBJECTIVE: To effectively use injection-compression sclerotherapy
      to treat patients with symptomatic vulvar varicosities. METHODS: Injection of
      vulvar varicosities with a 1% solution of sodium tetradecyl sulfate and
      subsequent compression therapy with the V2-Supporter was used to treat seven
      patients with symptoms of vaginal pressure, swelling, and pain. RESULTS: Three of
      the seven patients were premenstrual and four others were approximately 8 weeks
      post-vaginal delivery. Physical examination was performed in the upright as well
      as the dorsal lithotomy positions and injection was administered in the supine
      position. All patients noticed marked improvement in symptoms after treatment.
      CONCLUSION: We conclude that this technique has potential as a simple, effective
      way to treat symptomatic vulvar varicosities.

PMID- 9236877
TI  - Transverse sectioning of a pigmented lesion.

PMID- 9236878
TI  - Eccrine porocarcinoma.
AB  - Eccrine porocarcinoma is a malignant tumor of eccrine sweat glands. It is a very
      rare, slow growing tumor and clinically resembles other skin cancers. We report a
      case and review its clinical and pathological features. These tumors have a
      propensity for local recurrence, and wide excision with negative margins is
      recommended.

PMID- 9236879
TI  - Apocrine adenocarcinoma presenting as a large ulcerated axillary mass.
AB  - BACKGROUND: Apocrine adenocarcinomas are one of the rarest cutaneous cancers with
      few reported cases. Previously regarded nonspecifically as sweat gland tumors
      variants, they are now established as apocrine derivatives. Most occur in the
      axilla. OBJECTIVE: To provide a gross and histological description of an apocrine
      adenocarcinoma presenting in a 49-year-old African-American man. METHODS: The
      mass was removed en bloc with axillary lymph node dissection. The specimens were
      routinely embedded, and sectioned. Hematoxylin & eosin and periodic acid Schiff
      staining was done. Ploidy evaluation was performed by cytometry. RESULTS: The
      mass was firm, nontender, and mobile (15 x 14 x 7 cm) with overlying areas of
      ulcerated skin. It was closely associated with the axillary vessels, and
      latissimus dorsi and pectoralis major muscles, but was well circumscribed with
      extensive dystrophic calcification. Histological examination revealed an
      adenocarcinoma with predominant apocrine features. The tumor was arranged in
      solid sheets and large glands in the reticular dermis and had a loose trabecular
      pattern extending to the ulcerated skin surface. Two of seven local lymph nodes
      were positive for tumor; level two and three nodes were negative for tumor. DNA
      ploidy study determined the tumor to be an aneuploid cell line with an 18% S
      phase fraction. CONCLUSIONS: Tumor growth in this patient was rapid, histology
      unfavorable, and local nodes positive. However, aggressive surgical intervention
      resulted in 12 months follow-up without evidence of recurrence.

PMID- 9236880
TI  - Another case of spontaneous regression of Merkel cell (neuroendocrine) carcinoma.
AB  - BACKGROUND: Merkel cell (neuroendocrine) carcinoma (MCC) is a very aggressive
      primary cutaneous neoplasm most often occurring on the head and neck of the
      elderly. Spontaneous regression of MCC was first described in this journal in
      1986. Since then, other such cases have been reported. This case represents the
      sixth case of spontaneous regression of MCC. OBJECTIVE: To describe to clinical
      course in a patient with MCC who underwent spontaneous regression of metastatic
      disease. METHODS: Clinical records including detailed history and frequent follow
      up examination made this observation possible. RESULTS: Complete clinically
      evident regression of metastatic MCC was observed in this case. However, the
      patient received no treatment known to be effective for MCC. CONCLUSIONS:
      Spontaneous regression of MCC has been documented. The reason for regression is
      unknown. Further study of these rare cases may in the future provide more answers
      than questions.

PMID- 9236881
TI  - Treatment of adult port-wine stains using intense pulsed light therapy (PhotoDerm
      VL): brief initial clinical report.

PMID- 9236882
TI  - Venous thromboembolism and air travel.

PMID- 9236883
TI  - Stab avulsion of the short saphenous vein.

PMID- 9236884
TI  - About sclerotherapy in the U.S.

PMID- 9236885
TI  - Malignant melanoma occurring in chronic venous ulceration.

PMID- 9236886
TI  - On the danger of vertical sanding of vertical upper lip wrinkles.

PMID- 9236887
TI  - Epidermal disepithelialization by programmed diathermosurgery.

PMID- 9236888
TI  - Ductal carcinoma in situ of the breast--current management.
AB  - The management options in the treatment of patients with ductal carcinoma in situ
      of the breast are reviewed. Results of treatment by mastectomy, wide local
      excision, and local surgery followed by radiotherapy are analysed. Factors which
      incline the surgeon towards recommending mastectomy and the conditions which
      should be fulfilled for breast conservation are discussed.

PMID- 9236889
TI  - Evaluation of general practitioner referrals to a specialist breast clinic
      according to the UK national guidelines.
AB  - The recently published national guidelines to general practitioners for the
      referral of patients with breast problems were retrospectively applied to letters
      of all patients attending the Rapid Access Breast Clinic at the University
      Hospital of Wales. The patients have all had diagnostic investigations performed
      at the initial visit with a multidisciplinary review of results and provision of
      a management plan prior to the subsequent visit. Since its inception in May 1995
      until the end of the year when the guidelines were published, 2332 new patients
      had been seen. Overall, 29% of patients with benign breast disease would not have
      been referred if the guidelines had been strictly followed. Of the 147
      symptomatic carcinomas diagnosed from general practitioner referrals (6.3% of
      total referrals), no invasive cancers would have been missed. One patient with
      incidental detection of ductal carcinoma in situ (DCIS) in the asymptomatic
      contralateral breast would not have been referred. Referral for pain without a
      discrete lump constituted 63% of the patients with a benign diagnosis who fell
      outside the guidelines. The guidelines also include comprehensive algorithms for
      the initial management of benign breast symptoms that do not require immediate
      referral by the general practitioners. Our general practitioners were
      significantly better at referring patients over 50 years old but the proportion
      of appropriate referrals were not related to the number referred by each
      practice. The present guidelines adequately cover referral for the diagnosis of
      malignant breast disease to a specialist, and may reduce the benign workload of
      breast clinics.

PMID- 9236890
TI  - Radial scars: a review of 30 cases.
AB  - Radial Scars/Complex Sclerosing Lesions are benign breast lesions that are seen
      more frequently now with the advent of screening mammography. These lesions need
      to be excised surgically in the absence of classical diagnostic features.

PMID- 9236891
TI  - Experience with a high speed biopsy gun in breast cancer diagnosis.
AB  - Pre-operative determination of histology and receptor status is important in
      optimizing the management of breast cancer. The purpose of our study was to
      evaluate the high speed biopsy gun in 109 patients with palpable breast tumours.
      High speed biopsies were performed using the system BIP High Speed Multi 22 with
      16-gauge-needles at a speed of 30 m/s. All biopsies could be used for frozen
      sections and for determination of receptor status. In 81 patients (74.3%)
      malignant breast tumours were diagnosed, and three patients (2.8%) had highly
      suspicious lesions. The oestrogen receptor status was negative in 32%,
      progesterone receptor status negative in 41%. In one patient (0.9%) a high grade
      non-Hodgkin's lymphoma of B-cell-type was diagnosed. In 21.1% benign tumours were
      found. In one patient a malignant tumour was missed at biopsy (0.9% false
      negative). It was concluded that high speed biopsy is a reliable and simple
      method for preoperative sampling of breast lesions.

PMID- 9236892
TI  - The dynamics of serum thyroglobulin elimination from the body after thyroid
      surgery.
AB  - Thyroglobulin (Tg) is a glycoprotein produced exclusively by the thyroid. It can
      be found in the serum of healthy people as well as of those with various thyroid
      disorders. Elimination of Tg from the body occurs through the liver. The data on
      Tg serum half-life in the literature are scarce, and the reported values vary
      from 6-96 h. The aim of our study was to determine the Tg half-life after
      surgical removal of the thyroid gland. Knowing the exact half-life of Tg would
      enable rational timing of sampling serum for determination of Tg after thyroid
      surgery or chemotherapy and/or irradiation for evaluation of treatment in
      patients with differentiated thyroid cancer (DTC). In 11 patients (10 females and
      one male, aged 27-85 years) serum samples were taken 24, 48, 72 and 168 h after a
      near-total or total thyroidectomy. Serum Tg levels were determined and Tg half
      life calculated by the use of a one-compartment kinetic model. Mean Tg half-life
      was 65.2 h (SEM = 4.3), and Tg levels decrease below 5-10 ng/ml approximately
      only 25 days after thyroidectomy (7-10 x t1/2). Therefore, earlier determination
      of Tg cannot be used either for reliable detection of distant metastases or for
      evaluation of the effect of chemotherapy and/or irradiation.

PMID- 9236893
TI  - 10-year experience of total thyroidectomy with special reference to 85 thyroid
      cancers in one Italian centre.
AB  - The ideal surgical approach for differentiated thyroid carcinomas (DTC) is a
      matter for debate. Total (TT) or near total (NT) thyroidectomy on one side, and
      lobectomy (LL) or lobo-isthmusectomy (LI) on the other side are the options.
      Extended (TT, NT) resections are preferable for several reasons, and LL or LI are
      preferred by some groups. Our 10-year experience indicates that the post
      operative complications percentage may be low enough to make TT the preferred
      surgical option.

PMID- 9236894
TI  - Post-operative complications after completion thyroidectomy for differentiated
      thyroid cancer.
AB  - The surgical approach to differentiated thyroid carcinoma is still controversial,
      as many authors consider it necessary to remove the whole gland. Therefore, when
      definitive histological diagnosis is made following limited resection,
      reoperation and completion thyroidectomy (CT) is sometimes recommended. The main
      indications are for follicular cancer or for patients with a carcinoma of > or =
      1 cm previously treated with lobectomy or limited resection (early CT), or for
      local recurrence after previous treatment (late CT). Several authors, however,
      draw attention to the high rate of complications following completion
      thyroidectomy and advocate its use in more limited circumstances. The aim of the
      study was to evaluate the results of our experience with CT in the National
      Cancer Institute in Naples. Of 131 patients treated for thyroid cancer 35 (26.7%)
      underwent a CT. Re-operation was performed within 6 months in 26 cases (74.3%)
      and later in the remaining nine cases (25.7%): carcinoma in the residual gland
      was found in six cases (23%) of early CT, and in four cases (45%) in the late CT
      group with an overall incidence of 28.5%. Post-operative complications were:
      transient hypoparathyroidism, two cases (5.6%), permanent in one (2.8%).
      Transient recurrent laryngeal nerve palsy occurred in three patients (8.5%) and
      became permanent in one case (2.8%). Completion thyroidectomy can therefore be
      considered a safe procedure.

PMID- 9236895
TI  - A combined modality approach to the management of oesophageal cancer.
AB  - This study aims to update the experience of multimodality approaches in the
      management of oesophageal cancer that have been adopted in several Australian and
      New Zealand hospitals. Between 1984 and 1985, 92 patients received pre-operative
      radiotherapy (30-36 Gy over 3 weeks) and one of two chemotherapy regimes (one or
      two courses of i.v. cisplatin 80 mg/m2 plus a 4-5 day continuous i.v. of
      fluorouracil 5-800 mg/m2/day) concurrently prior to surgery. Eighty-two patients
      (89%) underwent resection as planned. Operative specimens were microscopically
      free of residual tumour in 18 patients. Eight patients (9%) had treatment-related
      deaths: seven from surgery and one due to pre-operative chemoradiation. The
      Kaplan-Meier 5-year cause-specific survival estimates were 32.9 +/- 7.8% for the
      58 patients with squamous cancer and 0% for the 32 with adenocarcinoma. Complete
      pathological response to the pre-operative regime was more common in females and
      was associated with a survival advantage. Five-year cause-specific survival
      expectation in patients who experienced a complete pathological response was 71.5
      +/- 12.4%, whereas it was only 15.9 +/- 5.6% in patients who had residual cancer
      in their surgical specimens. Although less toxic the pre-operative regime
      utilizing only one cycle of chemotherapy was no less efficacious either in
      producing a complete pathological response or in terms of survival expectation.
      This uncontrolled pilot study has produced encouraging long-term results,
      especially for patients with squamous carcinoma that experienced a complete
      response to pre-operative synchronous chemoradiotherapy. A randomized controlled
      study comparing surgery alone with (one cycle) chemoradiation followed by surgery
      is now underway.

PMID- 9236896
TI  - Histamine content in colorectal cancer. Are there sufficient levels of histamine
      to affect lymphocyte function?
AB  - Histamine has been found to stimulate growth of colorectal cancer in vitro and in
      vivo. Histamine has also been found to inhibit lymphocyte activity in vitro at
      concentrations greater than 10(-7) M. The aim of our study was to determine if
      the histamine concentrations in human colorectal cancer were sufficient to
      achieve these effects. We measured the histamine content in 31 colorectal cancer
      specimens using a radioenzymatic assay. Results were expressed as microgram
      histamine per gram of fresh tissue weight. Recovery and reproducibility studies
      were also carried out. The median histamine concentration in colorectal cancer
      tissue was 8.4 micrograms/g [7.6 x 10(-5)M], ranging from 0.3 microgram/g to 20.6
      micrograms/g. The high concentration of histamine in colon cancer is enough to be
      locally immunosuppressive.

PMID- 9236897
TI  - Neoadjuvant intra-arterial polychemotherapy of locally advanced rectal cancer.
AB  - In order to evaluate the usefulness of pre-operative intra-arterial selective
      polychemotherapy (PIASP), we carried out a retrospective study of 107 patients
      (65 males, 42 females) with locally advanced rectal cancer (LARC) (pT3-4 N0-1
      M0), who were treated between 1988 and 1991. Fifty-two patients (MG) underwent
      PIASP (Adriablastin 60-90 mg, fluorouracil 3-4 g) with subsequent radical
      surgery. Fifty-five patients (R0) received surgery alone. Angiographic findings
      after PIASP showed approximately 50-70% reduction in the vascular network in the
      tumour and surrounding tissues. A post-operative morphological study confirmed
      the considerable tumour dystrophy, necrobiosis and necrosis. Comparative
      statistical analysis in two patient groups showed that overall 5-year survival
      was significantly better in MG (64.76 +/- 1.85%) than in R0 (38.23 +/- 1.74%; chi
      2 = 9.1; P < 0.05). A similar situation was observed in all research subgroups:
      T3 N0 M0 (MG, 85.71 +/- 3.29% and R0, 65.63 +/- 2.85%; chi 2 = 2.61; P < 0.05);
      T3 N1 M0 (MG, 47.06 +/- 4.68% and R0, 0.0, chi 2 = 14.37; P < 0.05); T4 N0-1 M0
      (MG, 8.57 +/- 4.29% and R0, 0.0, chi 2 = 2.09; P < 0.05). Significantly better 5
      year survival rates were seen in MG than in R0 with the medial cellular
      differentiation in carcinoma (77.42 +/- 2.98% and 36.23 +/- 2.41%, chi 2 = 9.81;
      P < 0.05, respectively), the most frequent histological tumour structures. There
      is a trend for improved 5-year survival in low differentiation carcinoma (MG,
      47.62 + 5.29% and R0, 35.29 +/- 4.37%, chi 2 = 0.28, P > 0.05). The MG group
      showed eight local relapses of disease (15.38%), while the R0 group showed 21
      (38.1%), the MG group demonstrated 12 distant metastasis (23.07%) while R0
      demonstrated 19 (34.54%), the median relapse-free survival was 101.6 weeks in MG
      and 74.45 weeks in R0. The use of the combined PIASP with subsequent surgery
      treatment of patients with LARC allows a better prognosis than does surgery
      alone.

PMID- 9236898
TI  - Ras p21 protein immunoreactivity and its relationship to p53 expression and
      prognosis in gallbladder and extrahepatic biliary carcinoma.
AB  - Ras oncogene mutation is found in many human malignancies. The ras family of
      genes consists of three functional genes which encode highly similar, guanine
      nucleotide-binding, proteins (p21) of 21kDa, with GTPase activity. The p21
      protein is present on the inner aspect of the plasma membrane of a variety of
      cells. Using a polyclonal antibody, pan-ras p21 (Oncogene Science), the
      immunohistochemical expression of the ras oncogene in human gallbladder
      adenocarcinoma (n = 13) and dysplasia (n = 3), chronic cholecystitis (n = 11),
      common bile duct carcinoma (n = 6), together with ampullary carcinoma (n = 8) and
      carcinoma in situ (CIS) (n = 3), was examined. A statistically significant
      difference in ras p21 immunoreactivity between gallbladder cancers and chronic
      cholecystitis (P = 0.032; chi 2 test) was demonstrated. Strong ras p21
      immunoreactivity was present in most gallbladder carcinomas (n = 8; 62%) but not
      in the cases of gallbladder dysplasia (n = 1; 33%) or chronic cholecystitis (n =
      2; 18%). However, the ras p21 expression was strong in only a minority of the
      cases of ampullary carcinoma (n = 1; 13%), common bile duct carcinomas (n = 3;
      50%), and none of the ampullary CIS, and was not shown to be statistically
      significant. There was no statistically significant correlation between ras p21
      expression and patient survival (r = 0.18, r2 = 0.031, P = 0.56; simple
      regression analysis), or between ras p21 expression and p53 immunoreactivity (r =
      0.13, r2 = 0.017, P = 0.47; simple regression analysis). In conclusion, ras p21
      expression is increased in most cases of gallbladder carcinomas with no specific
      relationship to tumour grade suggesting that it may be important in the
      development of gallbladder carcinomas but not in its progression. No significant
      correlation was found between ras p21 expression and p53 immunoreactivity in
      gallbladder and biliary tract tumours and ras p21 immunoreactivity does not
      appear to be of any prognostic value. The lower rate of ras p21 overexpression in
      common bile duct and ampullary carcinomas suggests that these tumours may have a
      different molecular origin to gallbladder cancers.

PMID- 9236899
TI  - Treatment of humeral pathological fractures by internal fixation and
      methylmetacrylate injection.
AB  - Between 1986 and 1993, 18 patients with complete or impending fractures of the
      humerus were treated using Hacketall rods in association with semi-liquid
      methylmetacrylate after excision of the metastatic lesion. Methylmetacrylate was
      always injected proximally and distally to the curetted bone through drill holes.
      Fourteen patients had a pathological fracture and four presented with an
      impending lesion. The mean age at time of surgery was 62 years (range: 42-83).
      The primary tumour was a breast carcinoma in 10 cases, bronchogenic squamous cell
      carcinoma in three cases and hypernephroma, multiple myeloma, malignant melanoma,
      rectal adenocarcinoma and unknown primary tumour in one case each. The left arm
      was involved in seven cases and the right in 11. All patients experienced
      immediate relief from the pre-operative pain, although three patients complained
      of a residual discomfort during motion. In these three cases the residual pain
      can easily be managed with use of oral non-morphinic drugs. The functional aspect
      was not evaluated in two patients who died in the early post-operative period as
      a result of their general condition. In 15 patients, the post-operative range of
      motion was at least 80% of a normal humerus mobility. One patient encountered
      motion limitation because of an important lymph oedema. There was no infection,
      one patient had a temporary radial palsy with a complete restoration after a
      period of 5 days. No migration of the material was observed during an average
      follow-up of 9 months (range: 1-24).

PMID- 9236900
TI  - Post-operative brachytherapy: a prognostic factor for local control in epidermoid
      carcinomas of the mouth floor.
AB  - The aim of this study was to analyse the role of post-operative brachytherapy
      (BT) in a group of patients with a high risk of local relapse (positive or narrow
      surgical margins) for squamous cell carcinoma of the mouth floor (SCCFM). A
      comparison with post-operative external beam irradiation (EBI) in a group of
      patients with standard risk of local relapse for SCCFM with free margins is
      performed to estimate the benefit of BT. From 1979 to 1992, an initial group of
      32 patients with SCCFM (12, T1-2; 20, T3-4x) received an Ir 192 low dose rate BT
      using plastic tubes (+EBI for 20 patients) after surgery with positive or close
      margins. BT was applied in one or two planes to the surgical scar. The mean dose
      of BT was 57 Gy (range: 50-60) for exclusive BT and 22 Gy (range: 15-30) when a
      boost was applied (mean EBI dose = 50 Gy). During the same period, 36 patients
      had post-operative external irradiation alone after satisfactory surgical
      resection. Excluding the post-operative margin, these two groups were comparable
      for other prognostic factors. The mean follow-up was 46 months (range: 5-145)
      with a minimum follow-up of 2 years. For BT and EBI groups, the 5-year results
      (Kaplan-Meier) were, respectively, overall survival 62% and 43%, local control
      81% and 60% (P = 0.09) (log-rank) and severe complications 4/32 and 1/36. Post
      operative BT achieves good local control for patients with narrow or positive
      margins by increasing the dose to the surgical scar, with good tolerance. Given
      these encouraging results, we confirm this treatment for these patients.

PMID- 9236901
TI  - Cellular proliferation characteristics of basal cell carcinoma: relationship to
      clinical subtype and histopathology.
AB  - This study investigates the proliferation characteristics of 81 primary basal
      cell carcinomas (BCC) using detection of the Ki-67 antigen by
      immunohistochemistry. The tumours were classified into distinct sub-types based
      on their histological growth pattern and differentiation status. The mean Ki-67
      growth fraction was 0.293 and this was found to vary between the different growth
      patterns, with morpheic, infiltrating and superficial tumours showing the highest
      levels of proliferation at 0.373, 0.351 and 0.335, respectively; the nodular and
      micronodular growth patterns were significantly lower at 0.248 and 0.232,
      respectively. No overall association was seen between proliferation and
      differentiation status although certain histological growth patterns such as
      nodular showed a greater propensity to differentiate. Proliferation was related
      to tumour size, with larger lesions exhibiting higher growth fractions although
      this may have also been related to tumour subtype as infiltrating and morpheic
      tumours tended to present with larger tumour diameters. The spatial distribution
      of proliferating cells by Ki-67 labelling was not related to tumour subtype,
      differentiation or growth fraction. These studies have shown BCC to possess
      proliferative characteristics akin to other solid tumours commonly regarded as
      more rapidly dividing. There was an association between growth fraction and
      tumour subtype consistent with higher proliferation in the lesions considered to
      be more aggressive.

PMID- 9236902
TI  - Vincenz Czerny: carrying concepts into the 21st century.
AB  - Vincenz Czerny, as a pupil of Theodor Billroth and as head of the surgical
      departments of the Universities of Freiburg and Heidelberg between 1871 and 1906,
      markedly influenced the surgical development of the 19th century. Major
      contributions to the field of surgery included hernia operations, abdominal
      surgery and vaginal hysterectomy. Most importantly he recognized that surgery
      alone would not be able to control cancer and he developed concepts for
      multimodality treatment.

PMID- 9236903
TI  - The management of patients with advanced cancer (II).
AB  - In this second article in the series, obstruction of hollow viscera in patients
      with advanced malignant disease is discussed. The obstruction of such structures
      can be associated with the development of painful and incapacitating symptoms,
      often in patients who have a limited life expectancy. This obstruction may be
      caused by the primary tumour, compression from adjacent tumour-draining lymph
      nodes, the presence of metastases distant from the site of the primary tumour or
      to adhesions within the abdominal compartment (usually as a result of previous
      surgery). The organs most often affected are the oesophagus, the intestine (small
      and large), the biliary tree and the genito-urinary tract. Obstruction of each of
      these organs and its management is discussed in more detail below.

PMID- 9236904
TI  - Steroid hormones and cancer: IV. Prostate cancer.
AB  - Over many years, a great deal of attention has focused on the growth regulatory
      effects of androgens in prostate cells. This, has also prompted widespread
      interest in the role of these steroid hormones in prostate cancer pathogenesis.
      Even so, no-one has so far been able to identify the exact relationship between
      androgenic hormone levels and the risk of these diseases though differences in
      hormonal patterns amongst racial ethnic groups has been reported to reflect
      diversities in prostate cancer incidence. One of the difficulties stems from the
      fact that serum hormone levels do not reflect the changes observed in prostate
      tissue androgen concentrations as the normal prostate progresses to a disease
      state. In this article efforts will be directed towards understanding some of the
      intra-prostate-specific mechanisms responsible for activating and/or repressing
      the androgen-dependent gene network associated with the gradual transition to a
      hormone refractive neoplastic state.

PMID- 9236905
TI  - Long-term complete remission of melanoma liver metastases after intermittent
      intra-arterial cisplatin chemotherapy and surgery.
AB  - This paper presents the case of a female patient with liver metastases of a
      malignant melanoma showing complete remission after 10 courses of regional, intra
      arterial chemotherapy with cisplatin. The drug was administered as continuous
      infusion for 5 days. The daily dosage amounted to 30 mg/m2. The interval between
      courses was 6 weeks. Nausea and vomiting were seen after each course, while
      pathological serum creatinine levels only appeared after the eighth course. The
      only lesion in the liver still visible on CT scan after chemotherapy was removed
      by left hemihepatectomy. Meticulous histological examination revealed a big focus
      of necrotic tissue without any tumour cells. At the time of publication the
      patient is alive and disease-free over 9 years later.

PMID- 9236906
TI  - Invasive carcinoma in juvenile polyposis--report of a case in an African patient.
AB  - Since the 1980s it has been recognized that the polyps of juvenile polyposis have
      malignant potential. Since the introduction of colonoscopy this syndrome has been
      redefined and the hamartoma-adenoma-carcinoma sequence recognized. We believe
      this case is the first report of an invasive carcinoma associated with juvenile
      polyposis to be described in an African patient.

PMID- 9236907
TI  - Dermatofibrosarcoma protuberans of the upper lip: an overview and a case report.
AB  - Dermatofibrosarcoma protuberans is a slow-growing but locally aggressive
      malignant neoplasm of the skin. The preferential locations are on the trunk and
      proximal extremities but it can occur in the head and neck region in about 15% of
      the cases. This is a report of such a case and a review of the literature of head
      and neck cases attempting to analyse the profile of patients and surgical
      prognosis factors. The recurrence rate is important (20% to 55%) and dependent on
      the free tissue margins. Those margins are at least 3 cm in all directions; this
      is difficult to assess in the head and neck region because of both functional and
      cosmetic aspects. Distant metastases are rare but related to a long recurrence
      history. This behaviour gives the impression that prognosis is poorer for
      dermatofibrosarcoma in the head and neck than within other locations.

PMID- 9236908
TI  - Malignant melanoma of the penis.
AB  - A case of malignant melanoma of the penis is herein reported. Malignant melanoma
      of the penis is rare and accounts for a small percentage of malignant melanomas
      and of malignant penile lesions. The diagnosis is often delayed by the patient's
      reluctance to consult a physician and by the intrinsic difficulty in clinical
      diagnosis of such a rare neoplasm. The surgical treatment is not standardized and
      is shortly discussed. In general, prognosis is poor and most patients die within
      a few years due to distant metastasis.

PMID- 9236909
TI  - Human umbilical cord blood-derived eosinophils cultured in the presence of IL-3
      and IL-5 respond to fMLP with [Ca2+]i variation and O2- production.
AB  - In the presence of interleukin-3 and interleukin-5, eosinophil precursors from
      human umbilical cord blood mononuclear cells were regularly differentiated into
      mature eosinophil-like cells expressing normal morphology and cyanide-resistant
      peroxidase. O2- production and [Ca2+]i rise were measured in these in vitro
      differentiated eosinophils after fMLP stimulation; with dihydrorhodamine-123 and
      fura-2, respectively. Umbilical cord blood-derived eosinophils responded to fMLP
      (0.01 nM to 3 microM) with a concentration-dependent production of O2- (EC50 =
      63.1 +/- 17.2 nM; Emax = 71.0 +/- 6.2 pmol/min/10(6) cells). O2- production was
      correlated with an fMLP concentration-dependent increase in [Ca2+]i (EC50 = 32.5
      +/- 14.9 nM; Emax = 200.0 +/- 23.9 nM). These results indicate that human
      umbilical cord blood-derived eosinophils demonstrate functional characteristics
      similar to adult human peripheral blood eosinophils after activation by fMLP.
      Therefore, the large numbers of eosinophils (2-3 x 10(6)/ml cord blood) which can
      be obtained by culture of human cord blood mononuclear cells may serve as a
      useful model for future studies which will provide insight into the pathogenesis
      of diseases associated with eosinophils.

PMID- 9236910
TI  - Pilot scale purification of human monoclonal IgM (COU-1) for clinical trials.
AB  - No standard procedure is available for the purification of human monoclonal
      antibodies for human i.v. administration. Here we describe the procedure
      developed for pilot scale purification of the human IgM monoclonal antibody COU-1
      directed against a cancer-associated antigen. The hybridoma cells were grown in
      protein-free medium and purification from the clarified culture supernatant was
      carried out in 4 simple chromatographic steps: (1) hydroxylapatite
      chromatography; (2) hydrophobic interaction chromatography on phenyl-Sepharose:
      (3) cation-exchange chromatography on sulphonyl-Sepharose; and (4) anion-exchange
      chromatography on tetraethylamino-Sepharose. The product was substantially pure
      with regard to protein after step 3, but contained DNA which was removed in step
      4. The average recovery of the IgM was 54% with a range of 40-65%. Importantly,
      the ability of the antibody to bind to its antigen in ELISA was fully maintained
      during the purification. Subsequently, the purified antibody was isotope labelled
      and successfully used for in vivo detection of colon, rectal and pancreas
      carcinomas in patients. The purification procedure described appears to compare
      favourably with previously published methods, but a critical comparison is not
      possible due to the lack of necessary information in the available literature.

PMID- 9236911
TI  - A simple method for the propagation and purification of gamma delta T cells from
      the peripheral blood of glioblastoma patients using solid-phase anti-CD3 antibody
      and soluble IL-2.
AB  - Although gamma delta T cells make up no more than 10% of the peripheral blood
      mononuclear (PBM) cells, they appear to play an important role in host defense
      against tumor growth. In order to evaluate their functional activity against
      tumors and their response to various cytokines, large numbers of cells are
      required. Here, we describe a newly-devised method for the isolation and
      expansion of gamma delta T cells from the peripheral blood of cancer patients, in
      particular those with glioblastoma. Using this approach, a 1000-1500-fold
      increase in total cell numbers was achieved in two weeks, the proportion of gamma
      delta T cells in the expanded population being, on average, approximately 30%
      after 14 days of culture. The method therefore gives a yield of approximately 10
      15 x 10(8) gamma delta T cells from only 5 ml of peripheral blood from
      glioblastoma patients and normal controls. The highly purified gamma delta T
      cells of glioblastoma patients were shown to bear both a high-affinity
      interleukin-2 receptor (IL-2R) and a low-affinity IL-12 receptor (IL-12R). They
      also displayed significant cytotoxicity against autologous tumor cells, but not
      against autologous fresh or IL-2-treated lymphocytes, and proliferated in
      response to IL-2, both effects being dependent on the dose of IL-2 used for
      activation. In addition, overnight incubation with 700 U/ml of IL-2 or 50 ng/ml
      of IL-12 resulted in significant cytotoxic activity of patients' gamma delta T
      cells against K562 target cells, the level of activity being almost the same as
      with similarly-treated gamma delta T cells from normal controls (P > 0.05). These
      results demonstrate that the patients' gamma delta T cells obtained using this
      method are intact in terms of cytotoxic function. Thus, this method not only
      makes it possible to produce large numbers of purified gamma delta T cells but
      also to produce populations containing both gamma delta T cells and NK cells,
      both active against tumor targets which might be suitable for clinical trials of
      adoptive-immunotherapy, especially in cancer patients for whom no effective
      therapy is available.

PMID- 9236912
TI  - A simple method for the preparation and purification of C1 complement cleaved
      beta 2-microglobulin from human serum.
AB  - A simple method is described for the preparation of proteolytically processed
      forms of beta 2-microglobulin suitable for structural and biological studies. PEG
      6000 was added to the serum of healthy individuals to precipitate the C1
      complement complex from C1 esterase inhibitor (C1-inh). After dissolving the
      precipitate containing the C1 complement in Tris-HCl buffer, pH 7.6, efficient
      conversion of added beta 2-microglobulin to desLys58 beta 2-microglobulin was
      observed. Addition of a specific carboxypeptidase B inhibitor (Plummers
      inhibitor) could partly prevent the deletion of Lys-58 from cleaved beta 2
      microglobulin, whereby Lys58-cleaved beta 2-microglobulin was obtained. The
      proteolytically processed forms were subsequently purified by G-75 Sephadex gel
      filtration followed by chromatofocusing. A yield of 10-40% of proteolytically
      processed beta 2-microglobulin was obtained. Only one component was seen by SDS
      PAGE stained with Coomassie Brilliant Blue.

PMID- 9236913
TI  - A specific and sensitive ELISA for measuring S-100b in cerebrospinal fluid.
AB  - A sensitive, simple and specific sandwich ELISA for S-100b is described. This
      method involves the binding of a monoclonal anti-S-100b antibody to the wall of a
      microtitre plate. This capture antibody is subsequently incubated with S-100b
      standard, control or patient sample in the form of cerebrospinal fluid (CSF).
      After incubation, the microtitre plate is washed and horseradish peroxidase
      labelled polyclonal anti-S-100b is added (detector antibody). The amount of
      detector antibody bound to the microtitre plate is proportional to the amount of
      S-100b in the sample. The assay has a lower limit of detection of 0.04 ng/ml and
      shows < 0.006% reactivity with the closely related polypeptide S-100a. The assay
      has a mean within-batch precision of 9.3 and 5.6% at S-100b concentrations of
      0.38 and 0.8 ng/ml, respectively. The between batch precision is 8.9 and 8.1% at
      S-100b concentrations of 0.12 and 0.34 ng/ml, respectively. The recovery of S
      100b from CSF spiked with 0.5 ng/ml was 94% with a CV of 8.5%. The assay may be
      completed in less than 5 h using precoated microtitre plates, thus lending itself
      to routine use in clinical laboratories. Using this ELISA, 154 CSF samples were
      analysed and 19% of samples were found to have elevated levels. The highest
      levels were found in patients with cerebral haemorrhage or central nervous system
      malignancy. S-100b concentrations from individuals without evidence of
      neurological disease were found to be less than 0.4 ng/ml. Only 5% of patients
      with multiple sclerosis were found to have elevated CSF S-100b concentrations.
      Serial CSF samples taken from a patient with an infected in-dwelling shunt showed
      a dramatic decline, suggesting that S-100b is rapidly cleared.

PMID- 9236914
TI  - Importance of the linker in expression of single-chain Fv antibody fragments:
      optimisation of peptide sequence using phage display technology.
AB  - We have investigated the potential for enhancing the production of functional
      single-chain Fv antibody fragments (sFv), by altering the sequence of the linker
      that joins the variable domains of the molecule. To identify new functionally
      improved linkers we have used a phage display library containing a random
      sequence of six amino acids in the linker. Multiple rounds of panning on the
      antigen led to the selection of six different linker sequences that enhanced the
      binding of phage to the antigen. Five of the linkers also improved the secretion
      of soluble sFv by approximately five-fold. Analysis of the predominant linker
      sequence isolated showed that this improvement is not due to an increased
      affinity for the antigen, nor to alterations in the toxicity to bacteria. However
      the linker did affect the denaturation of the sFv in urea. It is therefore
      possible that the novel sequence helps in the refolding or secretion of the
      molecule.

PMID- 9236915
TI  - Flow cytometric quantitation of attachment and phagocytosis in phenotypically
      defined subpopulations of cells using PKH26-labeled Fc gamma R-specific probes.
AB  - Human receptors for IgG (Fc gamma R) are characterized by diverse structure and
      function. We describe a flow cytometric technique to quantitate receptor-specific
      Fc gamma R-mediated attachment and phagocytosis in phenotypically-defined subsets
      of cells using erythrocytes (E) labeled with the lipophilic dye PKH26 and coupled
      with biotin/avidin to either human IgG (myeloma proteins) or anti-Fc gamma R mAb.
      Using this technique and Fc gamma RIIa as a model, (1) we demonstrate sensitive
      and specific quantitation of attached and internalized E coupled to receptor
      specific mAb or natural ligand by monocytes within a peripheral blood leukocyte
      preparation; (2) we show the capacity to detect subtle allelic differences in Fc
      gamma R function; and (3) we demonstrate oxidant-induced enhancement of binding
      and internalization.

PMID- 9236916
TI  - Correlation between the avidity of mouse-human chimeric IgG subclass monoclonal
      antibodies measured by solid-phase elution ELISA and biospecific interaction
      analysis (BIA).
AB  - In order to validate a simple solid phase assay designed to measure antibody
      avidity, the avidities of chimeric mouse-human monoclonal antibodies specific for
      the hapten 4-hydroxy-3-nitrophenyl (NIP) were measured by a thiocyanate elution
      based ELISA method and compared to the binding kinetics as measured by
      biospecific interaction analysis (BIA). Despite possessing identical variable
      regions, the IgG2, IgG3 and IgG4 antibodies differed in their binding
      characteristics as measured by both techniques. Thiocyanate elution ELISA ranked
      the antibody avidity in the order IgG4 > IgG2 > IgG3. Biospecific interaction
      analysis permitted the determination of association and dissociation constants
      for the three chimeric antibodies. When compared, the affinity constants (K) of
      the three antibodies ranked in the following order; IgG4 > IgG2 > IgG3. The good
      agreement between the elution ELISA and BIA avidity ranking suggests that the
      simple ELISA method reflects the antibody binding characteristics for the three
      monoclonal antibodies investigated and thus may provide a simple technique to
      rank antibody avidity.

PMID- 9236917
TI  - Large scale and clinical grade purification of syndecan-1+ malignant plasma
      cells.
AB  - For cancer immunotherapy, it is usually necessary to obtain a large number of
      tumor cells from patients. We have previously reported that syndecan-I is present
      only on malignant plasma cells in samples from patients with multiple
      myelomatosis. We report here that this antigen is cleaved by chymopapain. This
      makes it possible to develop a rapid and clinical grade procedure to purify large
      numbers of myeloma cells using anti-syndecan-1 mAb, magnetic beads and
      chymopapain.

PMID- 9236918
TI  - A sensitive enzyme immunoassay of human thyroid-stimulating hormone (TSH) using
      bispecific F(ab')2 fragments recognizing polymerized alkaline phosphatase and
      TSH.
AB  - Bispecific F(ab')2 fragments recognizing both human thyroid-stimulating hormone
      (TSH) and alkaline phosphatase (ALP) were prepared by disulfide bond exchange
      between F(ab')2 fragments of IgG1 monoclonal antibodies (mAbs) against TSH and
      ALP, and were purified to homogeneity by hydrophobic interaction HPLC. ALP was
      polymerized by glutaraldehyde, and a new sandwich enzyme-linked immunosorbent
      assay (ELISA) for TSH was developed by using the ALP polymers and bispecific
      F(ab')2 fragments against TSH and ALP. In this assay, the preparation of
      covalently linked enzyme-mAb conjugates was not needed, and the interaction of
      mAb with non-specific proteins was greatly reduced by the use of F(ab')2
      fragments. The sensitivity for TSH was shown to increase in proportion to the
      degree of polymerization of ALP, and the lower detection limit obtained with the
      ALP trimer was 0.5 microU/ml. The sensitivity was 30 times or more higher than
      that of the conventional ELISA using covalently linked enzyme-mAb conjugates. The
      use of bispecific F(ab')2 permits the use of monomers and polymers of the signal
      enzyme and, thereby, regulates the sensitivity of the assay system.

PMID- 9236919
TI  - Multiple immunoblots after non-electrophoretic bidirectional transfer of a single
      SDS-PAGE gel with multiple antigens.
AB  - Western blotting is a very sensitive and powerful fundamental technique in
      immunology that has been used to detect and characterize proteins of low
      abundance. This technique employs the transfer of proteins separated on SDS-PAGE
      to nitrocellulose sheets for further detection using antibodies. Here we report
      the non-electrophoretic transfer of the 60-kDa Ro (or SSA) autoantigen, 240 and
      220 kDa spectrin antigens and prestained molecular weight standards from SDS-PAGE
      gels to nitrocellulose to obtain multiple immunoblots. In fact, we have used this
      procedure to obtain 12 immunoblots from a single gel with multiple sera.

PMID- 9236920
TI  - The use of Apostain in identifying early apoptosis.
AB  - Irradiated human peripheral blood lymphoid cells undergo apoptosis and
      progressively exhibit typical changes in light scatter and plasma membrane
      integrity that can be easily tracked by flow cytometry. Using this model, we
      assessed the capacity of a newly developed fluorochrome, Apostain, in identifying
      early apoptosis in unfixed samples. This probe is a plasma membrane permeant DNA
      dye that can be conveniently excited at 488 nm and has an emission wavelength >
      650 nm. To identify apoptotic cells, Apostain relies on the transient changes of
      chromatin texture that allow to accommodate more of a DNA dye occurring in early
      apoptosis. As early as 4 h after irradiation a proportion of cells showed an
      enhanced Apostain uptake. Consistent with their initial apoptotic nature, these
      cells had a still integer plasma membrane, as assessed by ethidium bromide, and
      unaltered light scatter. With time, cells showing the enhanced Apostain uptake
      started to bind dimly Annexin-V and, later, reduced their forward scatter. After
      18 h from irradiation, cells exhibiting a reduced forward scatter exhibited a
      bright staining with Annexin-V with a concomitant reduction in Apostain uptake,
      reflecting the gross chromatin disruption characterising the endpoint of
      apoptosis.

PMID- 9236921
TI  - Sentinel lymph node biopsy in malignant melanoma: the standard of care?

PMID- 9236922
TI  - Incorporation of 5-fluorouracil into hepatoma and normal tissue RNA at protein
      depletion in the rat.
AB  - BACKGROUND AND OBJECTIVES: 5-fluorouracil (5-FU) exerts its effects mainly by its
      incorporation into RNA and inhibition of DNA synthesis. Its toxicity may
      therefore be estimated by measuring its incorporation into RNA. Protein
      malnutrition has been considered to increase the toxicity of 5-FU. METHODS: Rats
      with a hepatoma implanted into the liver were fed on either a 25% or a 0% casein
      diet for 1 week. On the last day, they were infused via the hepatic artery with a
      therapeutic dose of 3H-5-FU. Its incorporation into RNA was measured in hepatoma
      and several normal tissues. RESULTS: Protein deprivation increased the
      incorporation of 5-FU into liver and intestinal RNA. Incorporation into hepatoma
      RNA did not increase significantly, but the ratio, liver/hepatoma RNA
      incorporation, remained unchanged. CONCLUSIONS: Protein deprivation might
      increase the toxicity of 5-FU on liver and intestine.

PMID- 9236923
TI  - p53 tumor suppressor protein and tissue proliferative fraction in infiltrating
      duct carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Breast cancer continues to frustrate oncologists
      worldwide. In India, it is the second most common neoplasm among women and is
      increasing in incidence. Several molecular markers have been associated with a
      poor prognosis in patients with breast cancer, and the presence of these markers
      is often thought to provide information on the biological behavior of the
      malignant breast tumor. Much attention has recently been focused on the tumor
      suppressor gene p53. Mutation or alteration in this gene leads to the loss of
      negative growth regulation and hence to rapid cell proliferation. The present
      study was designed to evaluate the connection between expression of the p53
      protein and its relation to the tissue proliferative compartment as measured by
      expression of the proliferating cell nuclear antigen (PCNA). METHODS: Expression
      of p53 and PCNA were detected by immunocytochemistry in paraffin-embedded
      sections of infiltrating duct carcinoma and control breast tissue (normal tissue
      and adenoma). RESULTS: A significant correlation was observed between expression
      of p53 and PCNA. A significant correlation was also observed between expression
      of p53 and grade of tumor and stage of disease. CONCLUSIONS: Our results support
      the hypothesis that accumulation of p53 is associated with a high tumor
      proliferation rate an association that might be expected in view of the role of
      wild p53 as a negative regulator of cell proliferation.

PMID- 9236924
TI  - Perineural invasion by ductal adenocarcinoma of the pancreas.
AB  - BACKGROUND AND OBJECTIVES: The correlation between various levels of perineural
      invasion by pancreatic carcinoma and the patient's prognosis has never been
      cleared. The authors carried out a histopathologic study of resected pancreatic
      carcinoma to elucidate the significance of a new histologic finding concerning
      perineural invasion, which we designated "intrapancreatic, extratumoral
      perineural invasion (nex)," and also to determine its predictive value for
      prognoses of patients after surgical removal of the tumor. METHODS: We
      investigated 90 patients with pancreatic adenocarcinoma who had undergone
      pancreatic resection. The prognoses of all patients were explored, and
      correlations between survival and pathologic factors were statistically examined
      for neural invasion. RESULTS: Nex was found in more than 50% of resected
      pancreases. A statistically significant association was found between the
      presence of nex and the grade of intrapancreatic neural invasion or the presence
      of extra-pancreatic neural plexus invasion. Nex was also found to be associated
      with patient survival after removal of the tumor. CONCLUSIONS: Nex appears to be
      an element predicting pancreatic cancer infiltration to the extrapancreatic nerve
      plexus and also to be a factor influencing postoperative survival of patients
      with pancreatic carcinoma.

PMID- 9236925
TI  - Preoperative laparoscopy in management of patients with carcinoma of the
      esophagus and of the esophagogastric junction.
AB  - BACKGROUND AND OBJECTIVES: Adequate preoperative staging of patients with
      esophageal and cardia carcinoma offers the potential for a rational choice of the
      therapy. The aim of this study was to assess the diagnostic value of laparoscopy
      compared to ultrasonography (US) and computed tomography (CT) in detecting intra
      abdominal metastatic spread. METHODS: Between November 1995 and December 1996, 36
      patients with adenocarcinoma of the cardia and 14 patients with squamous cell
      carcinoma of the lower third of the esophagus were studied with CT scan and US,
      followed by laparoscopy performed at the same session of planned surgical
      resection. Mean operative time of laparoscopy was 20 minutes (range 15-55 min).
      There was no mortality nor morbidity related to the laparoscopic procedure.
      RESULTS: Laparoscopy lead to a change of the therapeutic approach in five
      patients (10%): three patients with peritoneal carcinosis undetected at the
      imaging examinations, and one patient with advanced liver cirrhosis with signs of
      portal hypertension did not undergo resection; conversely, one patient with a
      liver hemangioma simulating a metastatic mass at CT/US underwent esophagogastric
      resection. Laparoscopy showed a higher sensitivity than US and CT in detecting
      peritoneal metastases (71% vs. 14% vs. 14%, respectively), macroscopic nodal
      metastases (78% vs. 11% vs. 55%), and liver metastases (86% vs. 71%).
      CONCLUSIONS: Laparoscopy represents a safe and effective diagnostic procedure in
      the preoperative staging of esophageal and cardia carcinoma; it provides the
      potential to avoid unnecessary exploratory laparotomies and to select the most
      appropriate treatment.

PMID- 9236926
TI  - Predictive factors for complete removal in soft tissue sarcomas: a retrospective
      analysis in a series of 592 cases.
AB  - BACKGROUND AND OBJECTIVES: In order to specify the indications for conservative
      surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS),
      we looked for the clinico-pathological parameters associated with the failure to
      obtain a complete removal (CRm) of the tumor. METHODS: We retrospectively
      analyzed a series of 592 cases of primary non-metastatic STS. Surgery was
      performed in 495 cases as a primary treatment and in 88 cases after chemo- or
      radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a
      univariate analysis, 20 parameters were tested for their association with CRm. A
      multivariate analysis was then used to define the independent parameters linked
      to the achievement of a CRm. RESULTS: In the univariate analysis, 15 parameters
      were found to be linked to the achievement of a CRm. Three of them proved to be
      independent in the multivariate analysis: T in the TNM classification, tumor
      location, and tumor necrosis. By the combination of these risk factors, four
      groups of patients were defined, with respective rates of CRm of 97% (no factor),
      95% (one factor), 70% (two factors), and 48% (three factors). CONCLUSIONS: The
      achievement of a CRm after surgery of STS depends not only on the accessibility
      of the lesion, but also on tumor aggressiveness, a reflection of which is
      necrosis. The detection of necrosis by imaging procedures may thus help
      predicting the resectability of tumors and defining the indications for
      neoadjuvant therapies, likely to broaden the use of conservative surgery.

PMID- 9236927
TI  - Tumor size as a prognostic indicator of histologic grade of soft tissue sarcoma.
AB  - BACKGROUND AND OBJECTIVES: Tumor size is one of the independent factors affecting
      prognosis of patients with soft tissue sarcoma (STS). We evaluated the
      significance of tumor size in combination with tumor depth in each histologic
      grade. METHODS: A total of 162 adult patients with localized STS in the
      extremities and trunk were selected. Patient ages ranged from 15 to 84 (median
      46.5) years with a male-to-female ratio of 1.19. Histologic grade of tumors was
      low in 53 cases, intermediate in 51, and high in 58. Two types of categorization
      were set, and their significance in predicting the prognosis of patients in each
      grade was evaluated. In the first category (intermediate grade), tumors were
      dichotomized at 10 cm: Group A comprised patients with deeply seated tumors
      measuring > 10 cm; Group B comprised patients other than those in Group A. In the
      second category (high grade), tumors were dichotomized at 5 cm: Group C comprised
      patients with deeply seated tumors measuring > 5 cm; Group D comprised patients
      other than those in Group C. RESULTS: Categorization was not useful in the
      prognosis of low grade tumors. In the intermediate grade group, the 5-year
      survival rate of Group B patients (78%) was higher than in Group A patients (59%)
      (P < 0.05), showing that dichotomization at 10 cm was useful. In the high grade
      group, the 5-year survival rate in Group C patients (32%) was lower than in Group
      D patients (56%), showing that dichotomization at 5 cm was useful. CONCLUSIONS:
      These findings show that tumor size for the prognosis of patients with STS
      differs according to each histologic grade.

PMID- 9236928
TI  - Tumor invasion and angiogenesis in early esophageal squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Although the relationship between angiogenesis and
      tumor proliferation or malignant potential has been previously demonstrated in
      several studies, early stage of cancer invasion and angiogenesis has seldom been
      investigated. METHODS: From the esophageal specimens of eight recently resected
      cases with esophageal squamous cell carcinoma, 25 areas of carcinoma-in-situ or
      microinvasive carcinoma were selected, and then a serial histologic investigation
      and immunohistochemical staining for the detection of Factor VIII-related antigen
      to investigate microvessels in the lamina propria mucosae beneath the lesions as
      a measure of angiogeneses and staining for laminin to visualize basement membrane
      was performed. Lymphocyte infiltration below the lesions were also estimated. In
      view of early cancerous invasion, histologic patterns of the growth of the
      lesions were divided into "flat," "expansive," and "downgrowth" patterns.
      RESULTS: Although downgrowth patterns are thought to be more invasive,
      relationships between the histologic patterns, and basement membrane staining
      patterns, and lymphocyte infiltration patterns were not demonstrated. However,
      the angiogenetic ratio (the number of vessels/cm under the lesions divided by
      that under normal epithelium) was observed to be significantly and closely
      related to tumor invasion patterns (P < 0.01), although it was not related to the
      destruction of the basement membrane or lymphocyte infiltration below the
      lesions. CONCLUSIONS: The angiogenesis of esophageal squamous cell carcinoma is
      closely correlated to the tumor invasion patterns in early esophageal cancerous
      lesions.

PMID- 9236929
TI  - Surgically curable and incurable scirrhous carcinomas of the stomach.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to identify a subgroup
      of patients with scirrhous carcinoma of the stomach who are more suitable for
      surgery by analysis of their clinicopathologic characteristics. METHODS: Seventy
      three patients with scirrhous gastric carcinoma who underwent gastrectomy between
      1979 and 1994 were included in the study. Clinicopathological characteristics of
      5-year survivors and nonsurvivors were compared. A multivariate analysis of
      various prognostic factors was performed. RESULTS: The 5-year survival rate was
      31.4%; 78% (28/36) of nonsurvivors died of malignant ascites and only 8% (3/36)
      died of hepatic or lung metastasis. When clinicopathologic parameters of 5-year
      survivors and nonsurvivors were compared, age, tumor size, macroscopic
      appearance, pT, pN, pM, stage, peritoneal lavage cytology, residual tumor, extent
      of gastric resection, operation time, volume of blood loss, and transfusion were
      significantly different. By the multivariate analysis, residual tumor,
      pathological depth of tumor infiltration, blood transfusion, and histological
      type were the independent prognostic factors. CONCLUSIONS: The prognosis of
      scirrhous carcinoma of the stomach is mainly determined by the depth of
      penetration and curability. In order to obtain better survival, early detection
      of tumor while it is limited to T2 stage appeared most important. Aggressive
      surgery would be indicated for T3 tumors, but in the case of T4 tumors, extent of
      operation should be determined by other factors such as extent of nodal
      metastasis or presence of distant metastasis.

PMID- 9236930
TI  - Argyrophilic nucleolar organizer regions: their value and correlation with
      clinical prognostic factors in breast carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Argyrophilic nucleolar organizer regions (AgNORs) have
      been recently identified as a marker of proliferative index in various tumors.
      These were evaluated in 46 patients with primary breast carcinoma and were
      correlated with clinical prognostic parameters of breast cancer. Ten patients
      with benign breast tumors served as controls in the study. METHODS: AgNORs were
      stained in paraffin sections of the tissues using Ploton's silver technique. For
      each specimen, the number of AgNORs, within the nuclei of 100 tumor cells were
      calculated. The average number of AgNORs per nucleus was calculated and the
      results expressed as mean +/- S.D. RESULTS: AgNOR count was significantly higher
      in breast carcinoma (6.61 +/- 1.75) than in benign breast tumors (1.88 +/- 0.19).
      Further, the AgNOR count in breast carcinoma showed a statistically significant
      increase in correlation with the increase in the size of the tumor, stage of the
      cancer, number of metastatic lymph nodes, and tumor recurrence at various sites.
      However, the differences in AgNOR count at different lymph node levels and
      histologic grading were not statistically significant. CONCLUSIONS: These results
      indicate that breast tumors with a higher AgNOR count, even at the initial stage,
      have a poor prognosis and require aggressive treatment for better control of the
      disease. Further, it is suggested that the patients with a benign tumor and more
      than three AgNORs per nucleus need careful surveillance.

PMID- 9236931
TI  - Leiomyosarcoma of the inferior vena cava: a clinicopathologic review and report
      of three cases.
AB  - BACKGROUND AND OBJECTIVES: We operated on three patients with leiomyosarcoma of
      the inferior vena cava. METHODS: Complete excision was possible in all three
      patients. RESULTS: One patient developed widespread metastasis at 23 months, one
      patient is alive with no evidence of disease at 70 months, and one patient is
      alive at 15 months. The third patient had subcutaneous and pulmonary metastases
      at the time of presentation, which are radiologically nondetectable at present
      following postoperative chemotherapy. CONCLUSIONS: The clinicopathologic
      features, prognostic factors, and treatment of 130 cases found in a comprehensive
      literature search and our three cases are reported.

PMID- 9236932
TI  - Clinical indications for brachytherapy.
AB  - Brachytherapy, or placing radioactive sources either temporarily or permanently
      into or near a malignant tumor, is a long-established cancer treatment method.
      During the past 25 years, brachytherapy has become safer and more versatile than
      earlier radium therapy, and its indications have increased dramatically during
      this period. One estimate is that at least 5-10% of all patients needing
      radiation therapy require brachytherapy. The site-specific clinical indications
      and methods for brachytherapy implementation are described.

PMID- 9236933
TI  - Transperineal ultrasound-guided prostate cryosurgery.

PMID- 9236935
TI  - Terminology related to Echinococcus and echinococcosis.

PMID- 9236934
TI  - High-dose rate intracavitary irradiation for carcinoma of the uterine cervix. The
      adverse effect of treatment prolongation.
AB  - AIM: To investigate the adverse effect of treatment prolongation on the local
      control and survival of the cervical carcinoma of the uterus. PATIENTS AND
      METHOD: Two hundred and sixteen patients with stage IIB and III cervical
      carcinoma treated with a combination of external radiation and high-dose rate
      (HDR) intracavitary irradiation between 1978 and 1989 were retrospectively
      studied. A multivariate analysis was used to determine the effect of treatment
      time on local control and survival. RESULTS: Overall treatment time was the most
      highly significant factors for local control in the multivariate analysis (p =
      0.0005). The 5-year cumulative relapse rates were significantly different with
      the treatment times 35 to 42 days: 9% versus 43 to 49 days: 19% versus 50 to 62
      days: 42% (p = 0.001). The second most significant parameter was stage
      classification (p = 0.02). Concerning relapse-free survival, stage classification
      (p = 0.0001), overall treatment time (p = 0.0035) and hemoglobin level (p =
      0.0174) were the 3 most important prognostic factors, although there was no
      relationship between treatment time and late complications. CONCLUSION: These
      results suggest that prolongation of treatment time is associated with decreased
      local control and survival in patients treated with external radiation and HDR
      intracavitary irradiation.

PMID- 9236936
TI  - Immunology of Echinococcus granulosus infections.

PMID- 9236937
TI  - Expression and immunological characterisation of Echinococcus granulosus
      recombinant antigen B for IgG4 subclass detection in human cystic echinococcosis.
AB  - A 165bp DNA fragment derived from the 12 kDa subunit of Echinococcus granulosus
      antigen B (AgB), a major hydatid cyst fluid antigen was cloned in the pMa1-c2
      expression vector. A 52 kDa maltose binding-AgB fusion protein (rAgB.MBP) was
      produced and inclusion bodies containing the fusion protein were solubilised in
      urea and affinity purified on an amylose-Sepharose 6B column. The immunogenicity
      of the purified recombinant antigen for IgG4 antibody detection was tested with
      human serum using immunoblotting, ELISA and dot-ELISA assays and compared to
      native AgB. Both recombinant and native AgB preparations were highly reactive for
      human IgG4 antibodies in serum of cystic echinococcus (CE) patients. Recombinant
      AgB.MBP (rAgB.MBP) showed approximately 65% sensitivity in detection of IgG4
      serum antibodies by ELISA from confirmed CE patients. Cross-reactivity (33%)
      occurred with alveolar echinococcosis (E. multilocularis) sera but recombinant
      AgB showed no seroreactivity with sera from other helminth infections tested
      (schistosomsis, onchocercsis, cysticercosis) or from uninfected individuals
      residing in CE endemic or non-endemic regions. The serologic sensitivity (63%)
      for IgG4 antibodies of a native AgB fraction enriched from human hydatid cyst
      fluid was similar to that for recombinant AgB (65%) though specificity was
      slightly lower (81%). A dot-ELISA for detection of total IgG, incorporating the
      rAgB.MBP resulted in 74% sensitivity and 88% specificity for human CE and 93%
      sensitivity and 65% specificity for native AgB. Recombinant AgB is a potential
      replacement for native antigens currently being used and could provide a better
      standardised E. granulosus specific test for clinical confirmation for CE
      especially for IgG4 antibody detection which appears to be predominantly
      associated with advanced disease.

PMID- 9236939
TI  - Polycystic echinococcosis in tropical America: Echinococcus vogeli and E.
      oligarthrus.
AB  - The paper reports available data on 72 known human cases of polycystic
      echinococcosis (PE) caused by Echinococcus vogeli (Ev) or E. oligarthrus (Eo).
      The patients' ages ranged from 6 to 78 years (median 44); one third were younger
      than 22 years and had severe lesions, demonstrating the aggressiveness of PE.
      There were no differences in occurrence between sexes. In 80% of the cases the
      lesions were in the liver alone or in combination with other organs; the rest
      were located in the lung or other single sites. The diagnosis of PE was based on
      the demonstration of polycystic larval cestode lesions by radiological imaging (X
      ray, US, CT scan) in patients born in tropical sylvatic areas of America where
      wild carnivores (canids, felids) and rodents (pacas and other species) were
      present. Serologic tests often, but not always, supported the diagnosis. Species
      identification of Ev or Eo were based on morphological characteristics of
      rostellar hooks from protoscoleces. The most common clinical presentation was
      abdominal; hard, round masses in or connected with the liver, hepatomegaly,
      increased abdominal size, pain, marked weight-loss and fever. Signs of portal
      hypertension were also present in 25% of cases, all of whom died of the disease
      or surgical complications following biliary drainage or partial hepatectomy. Ten
      percent were in asymptomatic persons. Albendazole treatment resulted in clinical
      improvement and disappearance or reduction of the size of lesions in some
      patients observed up to 24 months. The author believes that albendazole treatment
      should be tried before any other treatment is implemented. Human PE was reported
      from 11 countries, from Nicaragua to Argentina, 31 case were due to E. vogeli,
      three to E. oligarthrus (two orbital from Venezuela and Surinam and one cardiac
      from Brazil) and 38 were due to Echinococcus sp. (no rostellar hooks were
      available). PE reported from Nicaragua, Costa Rica, Chile, Argentina and Uruguay,
      countries outside the geographical range of the bush dog (only natural host of
      Ev) may have been due to Eo rather than to Ev. Several felids are known to serve
      as final host of Eo, and they are present in those areas. Epidemiological field
      studies of autochthonous human populations in tropical areas may contribute to
      early detection and make possible greater success in treatment of polycystic
      echinococcosis.

PMID- 9236938
TI  - Vaccination against echinococcus in perspective.
AB  - Vaccination of intermediate hosts will effectively reduce the prevalence of human
      echinococcosis. The rate of progress can be enhanced by concurrent tactical
      treatment of definitive hosts. The oncosphere of Echinococcus granulosus contains
      a specific protein which when expressed on the oncosphere surface will combine
      with specific antibody In the presence of complement, damage is caused to the
      plasma membrane, resulting in failure of the oncosphere to develop into a
      metacestode. Immunisation of sheep with oncosphere secretions or with an
      oncosphere homogenate results in 99% resistance to a challenge infection of the
      sheep with E. granulosus eggs. Immunisation of sheep with the specific purified
      protein results in 92% resistance. The gene coding for the protein has been
      isolated from an E. granulosus oncosphere cDNA library and expressed in E.coli as
      a fusion protein with glutathione-S-transferase. A monoclonal antibody to an
      epitope on the E. granulosus portion of the molecule is able to bind to the
      surface of oncospheres and to prevent their development to metacestodes in vitro.
      Immunisation of sheep with the fusion protein has given 97 and 98% resistance to
      a challenge infection in two separate trials. The shelf-life of formulated
      vaccine is at least 12 months, and the immunity generated by two injections given
      1 month apart persists for at least 12 months. A homologue of the gene has been
      identified in E. multilocularis. The vaccine has the potential to be used as a
      tool for control of transmission of E. granulosus through its natural
      intermediate hosts (particularly domestic ungulates) as part of hydatid control
      programmes. Traditional methods of hydatid control (anthelmintic treatment of
      dogs) require regular treatment within the prepatent period for prolonged periods
      (20-30 years) to achieve satisfactory control, and often sociological factors to
      do with dog-feeding, dog ownership and dog-control prevent such an achievement.
      By controlling the disease in both the definitive host and the intermediate host,
      the shortcomings of either procedure can be overcome, resulting in a cost
      effective desired result within a practical time period.

PMID- 9236940
TI  - Imaging of cystic echinococcosis.
AB  - This paper reviews various imaging techniques in different organs. Ultrasound is
      the most popular and readily available technique. Special emphasis is given to
      computerized tomography (CT) and magnetic resonance imaging (MRI) findings and
      their advantages for a confident diagnosis and treatment.

PMID- 9236941
TI  - Ultrasound imaging in cystic echinococcosis. Proposal of a new sonographic
      classification.
AB  - The ultrasonography permits the study of the natural history of cystic
      echinococcosis (CE) and evaluation of stages of the parasitic pathology. The
      evolution of abdominal CE was studied in 54 patients suffering from 97 abdominal
      cysts treated with albendazole, in 20 patients suffering from 20 hepatic cysts
      treated with echoguided percutaneous ethanol injection and in 39 patients
      suffering from 42 abdominal cysts, but left untreated. A new sonographic
      classification is suggested. Type I: Simple CE; (a) overall echofree; (b) with
      fine echos. Type II: Multiple CE; (a) multiple contiguous; (b) multiseptated with
      rosette, honeycomb and wheel-like pattern. Type III: With detachment of endocyst
      CE; (a) with double layer image; (b) with water-lily sign. Type IV: Mixed type
      CE; with fluid and solid aspect. Type V: Heterogeneous CE; (a) with ball of wool
      pattern; (b) with hypoechogenic image. Type VI: Hyperechoic CE; (a) with snow
      storm pattern; (b) with dyshomogeneous aspect. Type VII: Calcified CE; (a) with
      advanced calcification of the layer only; (b) with calcification of overall cyst.
      This classification appears more appropriate to the natural history of CE and
      permits a better differential diagnosis and more suitable treatment.

PMID- 9236942
TI  - Fine needle aspiration biopsy in the differential diagnosis of the liver cystic
      echinococcosis.
AB  - Liver cystic echinococcosis (CE) in non-endemic areas poses several problems in
      the differential diagnosis of various space occupying lesions detected by US
      examination. Fine needle aspiration biopsy (FNAB) using teflon covered needles
      with a US visible marker may be very useful for the definitive diagnosis. In the
      Clinic of Parasitic and Tropical Diseases in Poznan, FNAB were performed in 121
      patients with liver space occupying lesions, with an addition of an anthelmintic
      cover of albendazole. The biopsy material was examined parasitologically,
      cytologically, bacteriologically and immunologically. E. granulosus infection has
      been confirmed in 25 patients (20.6%), in 16 cases by finding parasite
      protoscoleces or hooks and in nine cases by detection of an antigen specific for
      E. granulosus, antigen 5 (Ag5). Additionally nine cases of malignancy (7.4%),
      four of angioma (3.3%) and three bacterial abscesses (2.5%) were diagnosed. There
      were no complications related to FNAB puncture. The algorithm of the clinical
      management of space occupying lesions suspected for CE was proposed. FNAB is a
      very important technique in the differential diagnosis of cystic echinococcosis.

PMID- 9236943
TI  - Public health importance of cystic echinococcosis in Latin America.
AB  - Human cystic echinococcosis (CE) caused by larval Echinococcus granulosus is a
      zoonosis of major public health importance throughout Latin America. The Andean
      and South Cone regions have been recognized as endemic areas of cystic
      echinococcosis. This paper reviews prevalence in Argentina, Chile, Uruguay,
      Brazil and Peru.

PMID- 9236944
TI  - Public health aspects of cystic echinococcosis in the Arab countries.
AB  - Human cystic echinococcosis (CE) caused by larval Echinococcus granulosus is a
      zoonosis of major public health importance throughout the region comprising Arab
      North Africa and the Middle East. Prevalence rates are determined by
      epizootiological factors related to the size of stray dog population and its worm
      burden and to the infection rates in the intermediate host reservoir livestock
      population. Socio-economic development and socio-cultural practices are
      considered important determinants in the continued transmission of the disease.
      The reasons why CE remains a significant public health problem in the region are
      summarized.

PMID- 9236945
TI  - Public health importance of cystic echinococcosis in China.
AB  - Cystic echinococcosis has been recorded in 21 out of China's 31 provinces,
      autonomous regions and municipalities (approximately 87% of territory). It
      constitutes one of the major public health problems, especially in several
      northwestern provinces and autonomous regions. This paper reviews the general
      situation, diagnosis, treatment, education and control programmes and
      international cooperation. Special attention is given to the Xinjiang, an endemic
      area about one sixth of the country's area with a human population of
      approximately 16 million.

PMID- 9236946
TI  - The WHO informal working group on echinococcosis. The Coordinating Board of the
      WHO-IWGE.

PMID- 9236947
TI  - A multicenter evaluation of new treatment efficacy instruments for Alzheimer's
      disease clinical trials: overview and general results. The Alzheimer's Disease
      Cooperative Study.
AB  - Evaluating treatment efficacy in Alzheimer's disease (AD) clinical trials
      requires optimal assessment methods to determine the extent and clinical
      meaningfulness of potential therapeutic effects of pharmacologic agents.
      Development of improved outcome measures for AD clinical trials is a major
      objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored,
      multisite clinical trials consortium. The ADCS Instrument Development Project
      evaluated the sensitivity, reliability and validity of new or improved measures
      in each of five assessment domains: (a) cognition (immediate and delayed memory,
      praxis, attention, and executive function); (b) clinical global change; (c)
      activities of daily living; (d) behavioral symptoms (agitation and other
      noncognitive symptoms); and (e) cognition in severely impaired patients. A total
      of 306 English-speaking subjects were enrolled in the study, including AD
      patients stratified by disease severity and cognitively normal, age-matched
      elderly subjects. Half were retested at 1 month and 2 months after baseline, and
      all received 6- and 12-month follow-up assessments. Spanish versions of these new
      measures are currently being evaluated. The development of this multisite study,
      the common methods and procedures, and a detailed description of the cohort are
      provided in this overview article. This multisite project demonstrates the
      feasibility of a consortium approach to instrument development. We were able to
      develop new instruments and efficiently evaluate their reliability and
      sensitivity to longitudinal change by capitalizing on the experience and patient
      resources of the participating ADCS research sites.

PMID- 9236948
TI  - Development of cognitive instruments for use in clinical trials of antidementia
      drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its
      scope. The Alzheimer's Disease Cooperative Study.
AB  - The cognitive assessment protocol of the Alzheimer's Disease Cooperative Study
      (ADCS) was designed to evaluate the reliability and validity of cognitive
      assessment measures that might be valuable additions to the Alzheimer's Disease
      Assessment Scale (ADAS) or other concise batteries used in antidementia drug
      trials. As part of an overall ADCS protocol to develop new instruments to be used
      in trials of treatments for Alzheimer's disease (AD), patients with mild to
      moderate AD and cognitively normal elderly were administered a battery of five
      tests at least three times over 1 year. The tests included word list learning
      with delayed free recall, a recognition memory test for faces, a series of letter
      and digit cancellation tests to measure concentration, tests of praxis, and a
      series of maze completion tasks designed to assess planning and executive
      function. A version of the digit cancellation task was reliable and sensitive to
      a broad range of dementia severity so that it could provide a useful addition to
      the present version of the ADAS. Performance on the word learning task with
      delayed recall and a subset of the mazes task were impaired even in mild AD, so
      these tasks may be useful in trials involving mild or at-risk subjects.
      Performances on the facial recognition task and on the praxis tasks were not
      related to dementia severity, so these tasks would not be useful to evaluate
      treatments. Therefore, the major outcome of this investigation was the
      identification of some potential additions to the present ADAS that extend both
      the cognitive domains and the range of symptom severity covered.

PMID- 9236949
TI  - Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical
      Global Impression of Change. The Alzheimer's Disease Cooperative Study.
AB  - This article reports the development and psychometric properties of the
      Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS
      CGIC). At present, a number of unvalidated CGIC scales are used in clinical
      trials, with various methods for making ratings. The ADCS-CGIC was designed on
      the basis of a survey of ADCS clinicians and by adapting existing instruments. It
      includes an organized but unstructured format, with which a clinician can address
      clinically relevant change. The instrument's reliability and validity were
      assessed in a prospective trial of Alzheimer's disease (AD) and healthy subjects
      over a 12-month period. It showed good short-term reliability at 1 and 2 months,
      with 90 and 94% of AD subjects, respectively, rated as having changed not at all
      or only minimally. The ADCS-CGIC's face validity was demonstrated by untreated.
      AD subjects rated as having worsened over time at both 6 months (56% rated as
      having worsened) and 12 months (81% rated as having worsened), whereas only 2% of
      control subjects showed minimal worsening. As a measure of predictive validity,
      ADCS-CGIC ratings at 12 months were significantly associated with change on four
      severity scales. As with other measures, change ratings were sensitive to
      dementia severity. Moderately impaired subjects showed greater worsening than
      other subjects. ADCS-CGIC ratings of greater worsening were made after the
      informant interview, regardless of whether informants or subjects were
      interviewed first. The ADCS-CGIC is a valid and reliable instrument for use in
      clinical trials.

PMID- 9236951
TI  - A longitudinal study of behavioral pathology across five levels of dementia
      severity in Alzheimer's disease: the CERAD Behavior Rating Scale for Dementia.
      The Alzheimer's Disease Cooperative Study.
AB  - As part of the Alzheimer's Disease Cooperative Study (ADCS) Instrument
      Development Project, the CERAD Behavior Rating Scale for Dementia (BRSD) was
      examined for its sensitivity to degree of cognitive impairment, its test-retest
      reliability, and its sensitivity to longitudinal change. Sixty-four normal
      elderly participants and 261 patients with AD stratified into severity groups
      based on Mini-Mental State Exam (MMSE) scores were rated on the BRSD at baseline
      and 12-month follow-up visits. A subset of subjects was evaluated at a 1-month
      follow-up visit. Baseline BRSD Total Score discriminated the normal group from
      each AD group, and mean Total Score significantly increased with increasing
      dementia severity. Test-retest reliability between baseline and 1-month Total
      Scores was satisfactory for all AD groups. Longitudinal change was evaluated by
      12-month change scores, which were significant in only the normal and in one AD
      group. From the results, we argue that the value of behavioral pathology
      assessment in clinical trials would be enhanced if additive scores were based on
      groups of correlated items rather than on a broad array of behaviors, some of
      which may increase and others may decrease in frequency as AD progresses.

PMID- 9236950
TI  - An inventory to assess activities of daily living for clinical trials in
      Alzheimer's disease. The Alzheimer's Disease Cooperative Study.
AB  - We developed a set of informant-based items describing performance of activities
      of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which
      ADL are useful for assessment of patients in clinical trials. Evaluation of ADL
      is an important outcome measure in AD clinical trials. For clinical trial
      measurement, ADL should have broad applicability, good test-retest reliability,
      scaling to cover a range of performance, and sensitivity to detect change in
      disease progression. A total of 45 ADL items developed from literature review and
      clinical experience were administered to informants of 242 AD patients and 64
      elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study
      Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and
      all at 6 and 12 months. Controls performed virtually all ADL items optimally at
      baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely
      applicable, i.e., performed at baseline or premorbidly by > 90% of subjects;
      showed good test-retest reliability between baseline and 1 and 2 months;
      correlated with MMSE scores of AD patients cross-sectionally; and showed a
      decline in performance from baseline to 12 months in at least 20% of AD patients.
      ADL could be identified that capture change in functional ability in patients
      across the entire range of the MMSE. The remaining 18 ADL included several that
      may be useful for trials that target specific populations, e.g., women with AD.
      Because change on specific items depends on baseline MMSE, ADL evaluation should
      include items relevant to the severity of dementia of patients enrolled in a
      clinical trial.

PMID- 9236952
TI  - Assessing patterns of agitation in Alzheimer's disease patients with the Cohen
      Mansfield Agitation Inventory. The Alzheimer's Disease Cooperative Study.
AB  - As part of the effort of the NIA Alzheimer's disease cooperative study to develop
      improved instruments for quantifying effects in Alzheimer's disease (AD) clinical
      trials, patterns of agitated behaviors were evaluated with the Cohen-Mansfield
      Agitation Inventory (CMAI) in 241 AD patients and 64 healthy elderly controls
      with valid baseline assessment on the CMAI. The test-retest reliability of the
      CMAI over 1 month was good (r = 0.74 to 0.92). Physically and verbally
      nonaggressive behaviors were most often reported, whereas physically aggressive
      behaviors were rare. Frequency of agitated behaviors increased with dementia
      severity, especially for patients with a Mini-Mental Status Exam score of 0-4.
      Agitation tended to increase in the evening with dementia severity for the more
      impaired patients. Amount of agitation did increase after 12 months in all but
      controls and mildly demented patients. The CMAI shows promise for evaluating a
      unique aspect of behavior and may be useful in assessing the effects of cognitive
      enhancers and other types of psychotropic drugs on behavior in dementia patients.

PMID- 9236953
TI  - The severe impairment battery: concurrent validity and the assessment of
      longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative
      Study.
AB  - Measurement of cognitive dysfunction in the early stages of Alzheimer's disease
      (AD) has been well studied and there are many objective tests in use for this
      purpose. However, with the exception of clinical rating scales, such as the
      Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional
      Assessment Staging, there are few objective measures of cognition in the more
      advanced stages of AD. Given a renewed interest in potential AD therapies,
      objective measures of mental functioning are needed to adequately assess change
      in more advanced AD patients. As part of an effort by the NIA-Alzheimer's Disease
      Cooperative Study to evaluate new measures of efficacy for their utility in
      treatment studies, the Severe Impairment Battery (SIB) was examined in a 1-year
      evaluation of change across a wide range of AD severity. The data suggest that
      the SIB is a reliable and valid measure of progression, particularly in persons
      with moderate to severe AD. The SIB may therefore be a useful outcome measure in
      clinical trials that include patients with more advanced stages of AD.

PMID- 9236954
TI  - The Spanish Instrument Protocol: design and implementation of a study to evaluate
      treatment efficacy Instruments for Spanish-speaking patients with Alzheimer's
      disease. The Alzheimer's Disease Cooperative Study.
AB  - Development of improved outcome measures for Alzheimer's disease (AD) clinical
      trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS),
      an NIA-sponsored, multisite clinical trials consortium. The ADCS is committed to
      recruiting and following minority patients in clinical trials. At present, a
      serious impediment to recruiting non-English-speaking minorities is the lack of
      instruments with adequate translation. Because Spanish is the second most
      commonly spoken language in the United States and because persons of Hispanic
      origin represent approximately 10% of the population, we conducted an instrument
      development protocol for Spanish-speaking patients. Evaluating treatment efficacy
      in Spanish-speaking AD patients requires the development of assessments that are
      comparable to those used for English-speaking participants in clinical trials.
      The ADCS Instrument Development Project evaluated the sensitivity, reliability,
      and validity of new or improved measures in each of five assessment domains: (a)
      cognition (immediate and delayed memory, praxis, attention, and executive
      function); (b) clinical global change; (c) activities of daily living; (d)
      behavioral symptoms (agitation and other noncognitive symptoms); and (e)
      cognition in severely impaired patients. These new treatment efficacy instruments
      were translated for Spanish speakers and a Spanish Instrument Study was conducted
      in parallel with the English version of the study. This report describes
      instrument translation, entry criteria, and recruitment procedures. In addition,
      the demographic and clinical characteristics of the cohort at baseline are
      presented and compared to the English-speaking cohort. Implications for the
      development of comparably sensitive Spanish language instruments are discussed.

PMID- 9236955
TI  - Multicenter evaluation of new instruments for Alzheimer's disease clinical
      trials: summary of results. The Alzheimer's Disease Cooperative Study.
AB  - The Instrument Development Project of the Alzheimer's Disease Cooperative Study
      (ADCS) evaluated new assessments in five domains: (a) cognitive function; (b)
      clinical global change; (c) activities of daily living; (d) behavioral symptoms,
      and (e) cognition in severely impaired patients. These new instruments
      demonstrate excellent discrimination between normal controls and patient groups
      and show adequate validity and reliability. Stability of measurement and
      sensitivity to longitudinal change were also demonstrated in each of these areas.
      Examination of several domain-specific questions also contributed new information
      on the measurement of cognitive function with different subtasks across AD
      severity levels, the stability of clinical ratings of global change, and the
      applicability of behavioral assessment across severity levels. The success of
      this project enhances the state of the art in the measurement of efficacy in AD
      clinical trials and also provides a basis for future research on improving AD
      outcome measures.

PMID- 9236956
TI  - Community health promotion: applying the science of evaluation to the initial
      sprint of a marathon.

PMID- 9236957
TI  - Community action for health promotion: a review of methods and outcomes 1990
      1995.
AB  - OBJECTIVE: Our objective was to explore the effectiveness of community action as
      a strategy for health promotion, through a critical review of five years of
      community action evaluation literature. METHODS: Community action was defined as
      a health promotion, program that involved the community in implementation and
      control of the process of the program. Criteria for scientific evaluation of
      programs were proposed for sampling and control procedures, reliability and
      validity of instruments, analysis techniques, and specification of details of the
      intervention. A critical review of the literature, located by an on-line and
      related reference search, was undertaken for community action aimed at reducing
      cancer and cardiovascular disease, between January 1990 and May 1995. RESULTS:
      None of seven community action studies (17 articles) that examined cancer risk
      factors fulfilled all the criteria for rigorous scientific evaluation. The most
      methodologically adequate cancer study, the COMMIT intervention, had only a
      moderate degree of success in reducing community smoking rates. Similarly, none
      of the six studies (25 articles) on cardiovascular disease fulfilled all the
      criteria. The results for the most methodologically adequate study, the Minnesota
      Heart Health Program, were disappointing, with strong secular trends preventing
      adequate assessment of the intervention effect. CONCLUSIONS: The finding that
      none of the reviewed studies met all evaluation criteria was due to several
      factors, including political considerations, feasibility, and the continued
      evolution of the science of evaluation in health promotion. Some important
      questions are posed for researchers by the failure of methodologically superior
      projects, such as COMMIT, to show major gains in reducing health risk behaviors.

PMID- 9236958
TI  - Conference report: community-based health promotion--state of the art and
      recommendations for the future.
AB  - The evaluators of the Henry J. Kaiser Family Foundation Community Health
      Promotion Grants Program in the West and the Foundation brought together 21
      researchers, funders, and community organizers with a variety of perspectives on
      community-based health promotion to share what has been learned to date and how
      that knowledge should be applied in the future. The two-day conference was
      divided into three sessions, covering conceptual, implementation, and evaluation
      issues. Specific topics were selected by the organizers with input from
      participants. Two papers were presented in each session, followed by comments
      from discussants and a general discussion involving the entire group. The
      dominant theme of the conference was the relationship between communities and
      outside institutions, focusing on problems with the current state of relations
      and how they might be improved in the future. All viewed building partnerships
      between communities and institutions as a desirable goal; however, the challenges
      involved in building effective partnerships are considerable and require a
      substantial investment to make them work. Recommendations that emerged from the
      discussions included explicitly acknowledging the diverse interests of the
      parties in community-based programs at the earliest stages of program planning;
      making a concerted effort to bridge the cultural gaps that exist among the
      parties; structuring funding to allow enough lead time for partnerships to
      develop or using social reconnaissance to identify strong existing partnerships;
      and integrating the evaluation more closely into the process of program
      development.

PMID- 9236959
TI  - Health promotion and disease prevention in integrated delivery systems: the role
      of market forces.
AB  - This article proposes a framework for the study of the effects of market forces
      on health promotion and disease prevention (HP/ DP) in integrated delivery
      systems (IDSs). We describe the evolution of IDSs in the United States and review
      the limited research on the extent to which IDSs have integrated HP/DP. We
      propose a typology of HP/DP activities that provides a comprehensive model of the
      types of HP/DP services and functions that an IDSs may incorporate. Finally, we
      identify and discuss the major market stages through which IDSs are
      transitioning, and within each market stage we identify the major forces that may
      influence IDS decisions to incorporate HP/DP services.

PMID- 9236960
TI  - The Australian National Asthma Campaign: effects of public education activities
      based on mass media.
AB  - INTRODUCTION: The National Asthma Campaign (NAC) was formed in 1990 as a
      coalition of the key professional organizations concerned with asthma and its
      management in Australia. It has conducted multifaceted educational activities
      targeting health care professionals, people with asthma, and the general public.
      Between November 1991 and March 1993, an educational mass media campaign was
      developed to inform people about new approaches to preventive asthma therapy and
      how people with symptoms of asthma should talk to their doctor or pharmacist
      about new management and monitoring strategies. Evaluation was based on McGuire's
      communication/persuasion model for assessing the impact of mass media campaigns.
      METHODS: Four serial cross-sectional population surveys of persons over the age
      of 18 years were conducted in four major Australian cities using structured
      telephone interviews. Information was sought on asthma campaign awareness and
      knowledge or use of appropriate asthma management practices. RESULTS: There was
      an increasing trend in awareness of asthma messages in the media and of
      appropriate message recall across the two-year period. Knowledge about the need
      to use preventive therapy for asthma improved significantly. Among those with
      asthma there was a significant upward trend in the proportion who discussed
      asthma with their doctor or pharmacist and who used peak flow meters and written
      asthma management plans. CONCLUSIONS: The net impact of the NAC and other
      activities has been an increase in awareness about asthma in Australia. These
      campaigns relied on the relatively nonselective medium of television to raise
      awareness and to start to change attitudes to asthma. The challenge is to build
      on these trends to further reduce morbidity and mortality due to asthma.

PMID- 9236961
TI  - Effects of a health promotion program on sustaining health behaviors in older
      adults.
AB  - BACKGROUND: Controversy exists regarding the optimal way to provide health
      promotion education to the elderly. This prospective randomized study evaluated
      the effectiveness of individualized assessment and counseling coupled with the
      receipt of a written health plan on client adherence to health behavior
      recommendations. METHODS: Two hundred thirty-seven ethnically diverse and
      predominantly low-income adults 60 and older, participating for the first time in
      an established statewide public health prevention program delivered in both rural
      and urban clinics, were recruited and randomly assigned to treatment and control
      groups. All participants received a standardized assessment that included a
      health history, nutrition assessment, and limited physical exam from a public
      health nurse. The treatment group additionally received a written personal health
      plan and individualized counseling to support implementation of the plan. Both
      groups were interviewed after one year to determine their adherence to the
      original recommendations. RESULTS: Seventeen preventive services and health
      behaviors were evaluated. There were no statistically significant differences
      between the groups on health care use and previous health behaviors at baseline.
      Using logistic regression and controlling for socioeconomic and demographic
      variables, we found that the treatment group that received a personal health plan
      and counseling completed significantly more preventive referrals and health
      behavior changes (P < .001). CONCLUSIONS: A client-centered planning process with
      supportive counseling by public health nurses, combined with health plans
      provided to clients, can significantly increase the prevention measures taken by
      older adults.

PMID- 9236962
TI  - Determinants of tick-avoidance behaviors in an endemic area for Lyme disease.
AB  - BACKGROUND: Tick bite control is an important initiative to prevent Lyme disease
      and other tickborne infections. While several studies have demonstrated that
      knowledge and awareness of Lyme disease in endemic areas are good, none has
      evaluated the relative importance of knowledge with other attitudinal and health
      belief variables to determine motivators of preventive behavior. METHODS: We
      conducted a cross-sectional analysis of 304 commuter ferry passengers departing
      Martha's Vineyard Island, Massachusetts, in August 1992, to ascertain the
      prevalence of tick-avoidance behaviors among individuals from an endemic area of
      Lyme disease and to identify the knowledge, behavioral, and demographic variables
      that best determine precautionary behavior. RESULTS: Overall, survey respondents
      (n = 304) had very good knowledge of Lyme disease (73% items correct on a
      knowledge test), but only 59% of respondents reported limiting time in tick
      areas, 58% usually wore protective clothing, 40% wore tick repellent, and 66%
      usually performed tick checks. By stepwise linear regression analysis,
      determinants of tick-avoidance behaviors included perceiving the behavior's
      benefits as outweighing its inconvenience (P < .0001), having confidence in
      recognizing Lyme disease symptoms (P < .0004), believing that Lyme disease is a
      serious illness (P < .0009), and believing that the avoidance behavior is
      effective in reducing the risk of Lyme disease (P < .01). Younger respondents (P
      < .05) performed fewer avoidance behaviors. Visitors (P < .0001) performed fewer
      tick checks than residents. Having confidence that one could find a tick on
      oneself with a tick check also predicted performance (P < .008). Increased
      general knowledge about Lyme disease did not predict any protective behaviors.
      CONCLUSIONS: Precautionary behaviors were underperformed in an at-risk population
      despite good knowledge of Lyme disease symptoms and transmission. Instead,
      performance was related to confidence in finding a tick on oneself and a
      perception that a precaution's benefit outweighed its inconvenience and would
      adequately reduce risk for Lyme disease. These data have implications for Lyme
      disease prevention programs, which typically focus on enhancing general knowledge
      as a means toward disease reduction.

PMID- 9236963
TI  - Components of the working well trial intervention associated with adoption of
      healthful diets.
AB  - INTRODUCTION: This report examines whether variability in the type and amount of
      the nutrition intervention in a worksite-based intervention could explain dietary
      outcomes. METHODS: Data are from 55 intervention worksites in the Working Well
      Trial, a randomized controlled trial of worksite-based health promotion. The
      components of the nutrition intervention were kickoff event, direct education,
      interactive activities (e.g., food sampling), contests, printed information
      picked up by employees, and materials distributed to employees. We measured
      delivery of the nutrition intervention (i.e., dose) by determining the amount of
      workforce participation in each intervention component. Diet outcomes were
      changes in intakes of fat, fiber, and servings of fruits and vegetables (reported
      on food frequency questionnaires). All variables were aggregated to the worksite
      level. We correlated the dose variables with indices of receipt of the
      intervention and with the dietary outcomes. RESULTS: Contests were associated
      with employee awareness of and participation in the nutrition intervention (r =
      0.49 and 0.28, respectively), and interactive activities were associated with
      intervention participation (r = 0.43). Contests were associated with increased
      fiber intake and fruit and vegetable consumption (r = 0.36 and 0.31,
      respectively), and direct education was associated with fruit and vegetable
      consumption (r = 0.38). All the above correlation coefficients were statistically
      significant (P < .05). Intervention dose was not associated with changes in fat
      intake. CONCLUSIONS: It appears that longer, interactive intervention efforts
      (contests and classes) resulted in more positive outcomes than did one-time
      activities (such as the kickoffs) or more passive efforts (use of printed
      materials). There is a need for studies designed to test worksite- and community
      based nutrition intervention methods.

PMID- 9236964
TI  - Do nutrition label readers eat healthier diets? Behavioral correlates of adults'
      use of food labels.
AB  - BACKGROUND: Reading and understanding nutrition labels on foods may be an
      important precursor to dietary change. However, little is known about how
      nutrition labels are used by consumers and what effect reading labels has on
      dietary behaviors. METHODS: This article identifies behavioral and health status
      correlates of nutrition label reading and describes patterns of label use among
      885 adult patients from four family medicine clinics in southeastern Missouri. To
      participate, patients completed a self-administered survey while waiting to see
      their physicians. RESULTS: Analyses revealed patients eating diets lower in fat
      were much more likely (51% versus 26%) than patients whose diets were higher in
      fat to report labels influencing their food purchase decisions, as were patients
      eating diets higher in fruits, vegetables, and fiber. Patients with high blood
      pressure were 63% more likely than those with normal or low blood pressure to
      look for sodium on the nutrition label (odds ratio [OR] = 1.63, 95% confidence
      interval [CI] = 1.35, 1.97), but no more likely to look for other nutrition label
      information. Similarly, patients with high cholesterol were more likely than
      those with normal or low cholesterol to look for saturated fat (OR = 1.39, 95% CI
      = 1.13, 1.72) and cholesterol (OR = 1.60, 95% CI = 1.29, 1.98) on the label, but
      no more likely to look for other nutrition label information. CONCLUSIONS:
      Findings consistently supported a relationship between patients' label reading
      and their dietary practices.

PMID- 9236965
TI  - Cholesterol awareness after case-finding: do patients really know their
      cholesterol numbers?
AB  - BACKGROUND: Patients who are informed of their cholesterol status have been shown
      to take steps subsequently to reduce their risks for coronary heart disease.
      Accordingly, as part of a population-based strategy to reduce disease burden due
      to high cholesterol, the National Cholesterol Education Program (NCEP) recommends
      that physicians tell all patients their cholesterol test results in a clear,
      understandable manner and encourage all patients, regardless of their risk factor
      status, to reduce their fat intake. OBJECTIVES: Our objective was to assess
      compliance with these NCEP recommendations at a 432-bed, Midwestern, university
      affiliated VA Medical Center. METHODS: We surveyed, within a year of their
      cholesterol measurement, 250 randomly selected men and women who had had their
      cholesterol checked by physician order between January 1993 and 1994. Survey
      results were validated against laboratory data. RESULTS: Approximately one third
      of the men and women said their cholesterol had not been checked, and about one
      half said they had not been told their test results. Only 59% knew their
      cholesterol status, and only 19% accurately recalled their cholesterol number.
      More than half did not remember receiving dietary advice. Female gender and more
      years of education were correlated with cholesterol awareness on both bivariable
      and multivariable analyses (adjusted odds ratio [OR] = 2.00, 95% confidence
      intervals [CI] = 1.10, 3.67 and OR = 2.62, 95% CI = 1.43, 4.78, respectively).
      Respondents were more likely to accurately recall their cholesterol number if
      they remembered being told their test results or remembered receiving dietary
      advice (OR = 7.70, 95% CI = 2.04, 29.0 and OR = 2.65, 95% CI = 1.15, 6.07,
      respectively). CONCLUSIONS: We conclude that compliance with the NCEP population
      based guidelines is poor. Physicians should endeavor to improve patients'
      awareness of their cholesterol status and be more diligent in prescribing dietary
      therapy.

PMID- 9236966
TI  - Preventing preterm birth and increasing access to prenatal care: two important
      but distinct national goals.

PMID- 9236967
TI  - Effect of Medicaid expansions on preterm birth.
AB  - OBJECTIVES: Inadequate prenatal care is thought to be a major modifiable risk
      factor for preterm birth, the leading cause of neonatal mortality. To improve
      high-risk women's financial access to prenatal care, the U.S. Medicaid program
      underwent major expansions during the 1980s. We evaluated these expansions over
      the nine-year period 1983 to 1991 in Tennessee to determine their effects on
      Medicaid enrollment, use of prenatal care, and preterm birth. METHODS: We used
      linked birth certificates, Medicaid data, and U.S. Census files to identify
      610,056 singleton births to African-American or Caucasian women in Tennessee
      whose last menstrual period was between 1983 and 1991. These were classified by
      maternal characteristics to identify groups with the greatest postexpansion
      increases in Medicaid enrollment, which should have benefited most from the
      policy changes. Study outcomes were Medicaid enrollment by delivery, enrollment
      in the first trimester, inadequate prenatal care (modified Kessner index), and
      preterm (< 37 weeks) birth. We calculated the changes (delta expressed as births
      per 100) between 1983 and 1991 in percentages of births with each of these
      outcomes. RESULTS: The expansions led to pronounced increases in maternal
      Medicaid enrollment by delivery (21% of births in 1983 to 51% by 1991) and in the
      first trimester (from 10% to 37%). Married women with < 12 years of education, <
      25 years of age, and < $12,500 mean neighborhood incomes (group 1) had the
      greatest increase, where enrollment and first-trimester enrollment increased from
      24% to 86% and 7% to 68%, respectively. In group 1, the percentages of births
      with inadequate maternal use of prenatal care decreased substantially, from 12.8%
      in 1983 to 6.4% in 1991, a reduction of 6.4 births per 100 (95% confidence
      intervals [CI] = -7.6, -5.3). However, the preterm birth rate did not decrease
      (9.1% in 1983, 9.4% in 1991, change of 0.3[-0.7 to 1.2] births per 100). For
      other births, there were lesser increases in Medicaid enrollment, correspondingly
      lesser decreases in inadequate use of prenatal care, but no reductions in preterm
      birth rates. CONCLUSIONS: In Tennessee, the Medicaid expansions materially
      increased enrollment and use of prenatal care among high-risk women, but did not
      reduce the likelihood of preterm birth.

PMID- 9236968
TI  - Evaluation of three methods for improving mammography rates in a managed care
      plan.
AB  - INTRODUCTION: Mammography has been shown to reduce breast cancer mortality among
      women 50 and older. Although mammography rates are increasing nationally, this
      effective screening tool remains underused. This study was conducted among 395
      women who were members of a network model health maintenance organization (HMO)
      in Philadelphia in order to determine which of three methods was most effective
      in increasing mammography rates: (1) a birthday card reminder only (the standard
      method); (2) a personalized letter from the medical director and materials
      promoting mammography; and (3) a multicomponent phone call incorporating a
      reminder, counseling, and scheduling of appointments. An additional goal was to
      determine whether the interventions were more or less effective depending on a
      woman's readiness to get a mammogram, as measured by stage of change. METHODS:
      Eligible women were randomized into one of three treatment groups described
      earlier. Mammography rates were calculated on the basis of a claims review and
      follow-up phone interviews after a period of six months. RESULTS: Women who
      received the telephone intervention were most likely to obtain a mammogram (28%);
      followed by the group that received the birthday card only (15%), and those who
      received the mailed intervention (9%). CONCLUSIONS: These results indicate that a
      multicomponent phone intervention is significantly effective in promoting
      mammography in managed health care plan members. An analysis by women's stage of
      change found a difference in the effectiveness of the three interventions among
      contemplators only.

PMID- 9236969
TI  - Preventive medicine physician satisfaction and its relation to practice
      characteristics.
AB  - BACKGROUND: Physicians specializing in general preventive medicine and public
      health manage programs, conduct research, and care for patients. This study
      examines their satisfaction overall and in five dimensions: contribution to
      people's lives, respect from physicians in clinical practice, research
      opportunities, income, and time to pursue outside interests. METHODS: A survey of
      1979-1989 graduates of preventive medicine residencies rated satisfaction on a
      five-point scale. Linear models were used to regress physician satisfaction
      against employer, hours worked, practice content, and other covariates. RESULTS:
      Respondents' (n = 778) overall job satisfaction was high, with 44% very
      satisfied, 44% satisfied, 7% neutral, and 6% dissatisfied. Federal government
      physicians had the highest satisfaction overall and for research opportunities
      and time for outside interests. Independent, statistically significant (p < .001)
      associations were found between higher satisfaction with research opportunities
      among academic and federal government employers, among Caucasians, and those with
      substantial epidemiologic practice; and lower satisfaction with time to pursue
      outside interests, more hours worked, and among women. CONCLUSIONS: Physician
      satisfaction could be understood in relation to a number of practice
      characteristics including its content, hours worked, income, and employer. The
      results suggest ways to improve physician satisfaction, including balancing
      competing demands of practice and focusing the physicians' responsibilities.

PMID- 9236970
TI  - Will patient satisfaction set the preventive services implementation agenda?
AB  - BACKGROUND: Patient satisfaction has become a measure of the quality of health
      care, and in highly competitive markets like the Twin Cities metropolitan area of
      Minnesota, it has become a health plan marketing tool. The purpose of this
      analysis is to examine whether the known association between preventive services
      and patient satisfaction might spontaneously lead clinicians to recommend
      preventive services at greater rates. DESIGN: We conducted a mail survey of a
      stratified random sample (n = 6,830) of adult patients who had recently visited a
      physician in one of 44 clinics in and around Minneapolis-St. Paul, Minnesota. The
      main outcome measures are patient-reported rates of being advised to have eight
      preventive services, patient satisfaction with preventive services, patient
      satisfaction with overall health care, and correlations among these variables.
      RESULTS: Self-reports of being advised to have a preventive service when due were
      correlated with higher levels of satisfaction with that specific service only at
      levels of r = 0.16 to r = 0.35. They were correlated at levels of r = 0.01 to r =
      0.27 with the Group Health Association of America satisfaction index.
      CONCLUSIONS: Although there is a positive association between being advised to
      have a preventive service on the one hand and reporting satisfaction with care on
      the other, this association appears too weak to spontaneously stimulate
      physicians to recommend preventive services to their patients. This suggests
      that, if preventive services are to be delivered at higher rates, they must
      become an explicit component of quality evaluations.

PMID- 9236971
TI  - Physical activity in childhood and adolescence as predictor of physical activity
      in young adulthood.
AB  - BACKGROUND: Despite the general belief that physical activity in childhood and
      youth is an important prerequisite for the physical activity in adulthood, there
      is not much information based on reliable longitudinal studies about the
      continuity of physical activity from childhood and adolescence to adulthood.
      METHODS: As a part of a national-level research program called "Cardiovascular
      Risk in Young Finnus," we studied to what extent leisure-time physical activity
      at the age of 9, 12, 15, and 18 predicts physical activity nine and 12 years
      later. A total of 610 9-year-old, 624 12-year-old, 572 15-year-old, and 503 18
      year-old boys and girls were studied in 1980. A follow-up measurement was carried
      out with the same subjects in 1983, 1986, 1989, and 1992. Accordingly, in 1992
      they were 21, 24, 27, and 30 years of age. These data concern only the
      measurements taken in 1980, 1989, and 1992. Physical activity was measured by
      means of a short questionnaire. A sum index of physical activity (PAI) was
      computed with the help of five variables. RESULTS: The correlations between the
      indices derived in 1980 and 1989, and between those derived in 1980 and 1992,
      were, with the exception of one group, significant but low varying within a nine
      year interval from .18 to .47, and within a 12-year interval from .00 to .27.
      Corresponding multiple correlations varied from .18 to .53 and from .18 to .30.
      Participation in competitive sport and the physical education grade were the best
      predictors of later physical activity. CONCLUSIONS: The results gave support to
      the conclusion that persistent participation in sport in particular increases the
      probability of a higher level of physical activity in later life.

PMID- 9236972
TI  - Primary care physicians' perceptions of adolescent pregnancy and STD prevention
      practices in a Nova Scotia county.
AB  - INTRODUCTION: This study was carried out to determine the predisposing, enabling,
      and reinforcing factors related to practice behaviors in the prevention of
      adolescent pregnancy and sexually transmitted diseases (STDs), and to assess
      physicians' "ideal" history taking and service provision versus their actual
      practice in this clinical area. METHODS: Twenty-six of 37 physicians in a single
      county in Nova Scotia took part in a face-to-face interview. RESULTS: Analysis of
      predisposing factors found that, for seven of 10 areas related to knowledge of
      the epidemiology of adolescent pregnancy and STDs, fewer than 50% of male
      physicians were able to give correct responses. All physicians believed this to
      be an important area for prevention, and 89% that prevention is possible, but
      only 62% believed that their own prevention efforts are effective. Respondents
      were about equally likely to view schools and physicians as having responsibility
      for prevention of adolescent pregnancy and STDs. Significant enabling factors
      included high levels of perceived personal comfort and skill, but time factors
      and opportunities to interact with adolescents sufficiently frequently to carry
      out prevention were seen as barriers. Most physicians (68%) agreed that the
      physician fee schedule was a negative reinforcing factor. Male physicians and
      those in rural practice were significantly more likely to have larger gaps
      between those preventive practices they saw as desirable and those they actually
      performed.

PMID- 9236973
TI  - Whitaker Lecture 1996: microcirculation, biomedical engineering, and artificial
      blood.
AB  - The development of artificial blood requires the understanding of how blood
      behaves at the level of the microcirculation. A number of measuring systems have
      recently become available that allow analysis of the transport properties of
      blood and the microvessels in terms of pressure, flow, the dynamics of their
      diameter changes, and the rate and manner of oxygen delivery. Findings from this
      technology have led to the development of an analytical framework with which to
      assess the consequences of altering the physical properties of blood and to
      verify quantitatively theoretical predictions. Results show that blood viscosity
      and oxygen-carrying capacity are directly related, and must be jointly modified
      in a prescribed manner to maintain tissue oxygen delivery. The use of optical
      techniques to assess flow and oxygen delivery in experimental animal models show
      that the consumption of oxygen by the microvessel wall is an important
      determinant of tissue oxygenation. Furthermore, the viscosity of blood and/or the
      mixture of blood and an artificial substitute must achieve a viscosity that is
      close to normal. Low blood viscosity is not necessarily beneficial, unless blood
      flow velocity rises to maintain the shear stress at the wall needed for the
      generation of local vasodilators. Manipulating physical properties of currently
      available modified hemoglobins by mixing them with conventional plasma expanders
      yield fluids that may provide optimal blood replacements.

PMID- 9236975
TI  - Simulation of human thermoregulation during water immersion: application to an
      aircraft cabin water-spray system.
AB  - A model was developed of transient changes in metabolic heat production and core
      temperature for humans subjected to cold conditions. It was modified to predict
      thermal effects of the upper parts of the body being sprayed with water from a
      system designed to reduce the smoke effects of an airplane fire. Temperature
      changes were computed at 25 body segments in response to water immersion, cold
      air exposure, and windy conditions. Inputs to the temperature controller were:
      (a) temperature change signals from skin segments and (b) an integrated signal of
      the product of skin and head-core (hypothalamic) temperature changes. The
      controller stimulated changes in blood flow to skin and muscle and heat
      production by shivering. Two controller parameters were adjusted to obtain good
      predictions of temperature and heat-production experimental data in head-out,
      water-immersion (0 degree-28 degrees C) studies in humans. A water layer on the
      skin whose thickness decreased transiently due to evaporation was added to
      describe the effects of the water-spray system. Because the layer evaporated
      rapidly in a very cold and windy environment, its additional cooling effect over
      a 60-min exposure period was minimal. The largest additional decrease in rectal
      temperature due to the water layer was < 1 degree C, which was in normal
      conditions where total decreases were small.

PMID- 9236974
TI  - Nonlinear model for capillary-tissue oxygen transport and metabolism.
AB  - Oxygen consumption in small tissue regions cannot be measured directly, but
      assessment of oxygen transport and metabolism at the regional level is possible
      with imaging techniques using tracer 15O-oxygen for positron emission tomography.
      On the premise that mathematical modeling of tracer kinetics is the key to the
      interpretation of regional concentration-time curves, an axially-distributed
      capillary-tissue model was developed that accounts for oxygen convection in red
      blood cells and plasma, nonlinear binding to hemoglobin and myoglobin,
      transmembrane transport among red blood cells, plasma, interstitial fluid and
      parenchymal cells, axial dispersion, transformation to water in the tissue, and
      carriage of the reaction product into venous effluent. Computational speed was
      maximized to make the model useful for routine analysis of experimental data. The
      steady-state solution of a parent model for nontracer oxygen governs the
      solutions for parallel-linked models for tracer oxygen and tracer water. The set
      of models provides estimates of oxygen consumption, extraction, and venous pO2 by
      fitting model solutions to experimental tracer curves of the regional tissue
      content or venous outflow. The estimated myocardial oxygen consumption for the
      whole heart was in good agreement with that measured directly by the Fick method
      and was relatively insensitive to noise. General features incorporated in the
      model make it widely applicable to estimating oxygen consumption in other organs
      from data obtained by external detection methods such as positron emission
      tomography.

PMID- 9236976
TI  - Regulatory interaction between myogenic and shear-sensitive arterial segments:
      conditions for stable steady states.
AB  - Myogenic and shear stress-sensitive mechanisms control the caliber of a small
      blood vessel in this modeling study. This blood vessel in our model was composed
      of a pressure-sensitive (myogenic) component and a series-connected shear
      sensitive component. The response of this model to imposed pressure and the
      conditions that result in a stable steady-state vessel diameter were
      investigated. The requirement that the model parameters need to satisfy for a
      stable steady state to exist are expressed by the numerical solution of
      simultaneous nonlinear equations. Also, if a vessel is put into an initial state
      that is not an equilibrium state, then the system must occupy a range of initial
      conditions to arrive at a stable equilibrium. These are described graphically for
      three cases. In general, the initial shear stress should be higher than the
      equilibrium value of shear stress, and/or the initial transmural pressure should
      be low, compared with the imposed feed pressure. Increasing the imposed pressure
      on the vessel can lead to elimination of the equilibrium state and vasospasm,
      according to this model. When a stable steady state is not reached, the model
      predicts elimination of the vessel or vasospasm. The model is in qualitative
      agreement with experimental observations that, during angiogenesis, vessels with
      low flow are often eliminated.

PMID- 9236977
TI  - The importance of slice location on the accuracy of aortic regurgitation
      measurements with magnetic resonance phase velocity mapping.
AB  - Although several methods have been used clinically to evaluate the severity of
      aortic regurgitation, there is no purely quantitative approach for aortic
      regurgitant volume (ARV) measurements. Magnetic resonance phase velocity mapping
      can be used to quantify the ARV, with a single imaging slice in the ascending
      aorta, from through-slice velocity measurements. To investigate the accuracy of
      this technique, in vitro experiments were performed with a compliant model of the
      ascending aorta. Our goals were to study the effects of slice location on the
      reliability of the ARV measurements and to determine the location that provides
      the most accurate results. It was found that when the slice was placed between
      the aortic valve and the coronary ostia, the measurements were most accurate.
      Beyond the coronary ostia, aortic compliance and coronary flow negatively
      affected the accuracy of the measurements, introducing significant errors. This
      study shows that slice location is important in quantifying the ARV accurately.
      The higher accuracy achieved with the slice placed between the aortic valve and
      the coronary ostia suggests that this slice location should be considered and
      thoroughly examined as the preferred measurement site clinically.

PMID- 9236978
TI  - A model of blood interaction with optical-fluid guide for laser angioplasty.
AB  - A mathematical model is developed to describe the flow and mixing of blood and
      optical fluid used in liquid-guided light for laser angioplasty. The model is
      based on a two-fluid formulation in which separate transport equations are solved
      for the blood and the optical fluid. Empirical relations, established in prior
      work, are used to represent interfluid transport of momentum. Both steady and
      phasic inflow conditions are considered. Parametric calculations are performed
      showing effect of relative flow rates of blood and optical fluid, on the mixing
      phenomena. The relative velocity considered (based on average blood velocity)
      ranged from 0.08 to 0.28 m/sec. No allowance has been made for ablation of the
      plaque. The predicted results include spatial distribution of the velocity field
      and the existence probabilities (volume fractions) that provide a measure of the
      extent of mixing between the fluids. It is found that the degree of mixing is
      adversely affected by the relative inflow velocity between blood and optical
      fluid and the pulsatility of blood inflow. Deep penetration of the optical fluid
      is predicted at high relative velocity and at the end of diastolic and early
      systolic stages of the cardiac cycle.

PMID- 9236980
TI  - A small angle light scattering device for planar connective tissue
      microstructural analysis.
AB  - The planar fibrous connective tissues of the body are composed of a dense
      extracellular network of collagen and elastin fibers embedded in a ground matrix,
      and thus can be thought of as biocomposites. Thus, the quantification of fiber
      architecture is an important step in developing an understanding of the mechanics
      of planar tissues in health and disease. We have used small angle light
      scattering (SALS) to map the gross fiber orientation of several soft membrane
      connective tissues. However, the device and analysis methods used in these
      studies required extensive manual intervention and were unsuitable for large
      scale fiber architectural mapping studies. We have developed an improved SALS
      device that allows for rapid data acquisition, automated high spatial resolution
      specimen positioning, and new analysis methods suitable for large-scale mapping
      studies. Extensive validation experiments revealed that the SALS device can
      accurately measure fiber orientation for up to a tissue thickness of at least 500
      microns to an angular resolution of approximately 1 degree and a spatial
      resolution of +/-254 microns. To demonstrate the new device's capabilities,
      structural measurements from porcine aortic valve leaflets are presented. Results
      indicate that the new SALS device provides an accurate method for rapid
      quantification of the gross fiber structure of planar connective tissues.

PMID- 9236979
TI  - An in vitro traumatic injury model to examine the response of neurons to a
      hydrodynamically-induced deformation.
AB  - A novel in vitro system was developed to examine the effects of traumatic
      mechanical loading on individual cells. The cell shearing injury device (CSID) is
      a parallel disk viscometer that applies fluid shear stress with variable onset
      rate. The CSID was used in conjunction with microscopy and biochemical techniques
      to obtain a quantitative expression of the deformation and functional response of
      neurons to injury. Analytical and numerical approximations of the shear stress at
      the bottom disk were compared to determine the contribution of secondary flows. A
      significant portion of the shear stress was directed in the r-direction during
      start-up, and therefore the full Navier-Stokes equation was necessary to
      accurately describe the transient shear stress. When shear stress was applied at
      a high rate (800 dyne cm-2 sec-1) to cultured neurons, a range of cell membrane
      strains (0.01 to 0.53) was obtained, suggesting inhomogeneity in cellular
      response. Functionally, cytosolic calcium and extracellular lactate dehydrogenase
      levels increased in response to high strain rate (> 1 sec-1) loading, compared
      with quasistatic (< 1 sec-1) loading. In addition, a subpopulation of the culture
      subjected to rapid deformation subsequently died. These strain rates are relevant
      to those shown to occur in traumatic injury, and, as such, the CSID is an
      appropriate model for studying the biomechanics and pathophysiology of neuronal
      injury.

PMID- 9236981
TI  - Controlling receptor/ligand trafficking: effects of cellular and molecular
      properties on endosomal sorting.
AB  - Receptor-mediated endocytosis is the process by which cells internalize ligands
      that have specifically interacted with cell surface receptors. Within
      intracellular endosomal compartments, receptor/ligand complexes can be targeted
      to lysosomes for degradation, recycled back to the plasma membrane, or sorted
      separately to these destinations. We have developed a mechanistic mathematical
      model that can account for the spectrum of experimentally observed endosomal
      sorting outcomes. The central hypothesis of this model is that receptors may be
      selectively retained by putative endosomal retention components and that this
      process may be modulated by receptor occupancy. This hypothesis is supported by
      the recent discovery of an endosomal retention component involved in targeting
      epidermal growth factor receptors to lysosomes. In this paper, we use the model
      to predict how changes in key cellular and molecular parameters alter sorting
      outcomes. This analysis provides guidance for rationally modulating the sorting
      process in a variety of biomedical applications, either by the manipulation of
      cellular parameters or the design of ligand properties.

PMID- 9236982
TI  - Automatic discrimination of myoelectric signals via parallel cascade
      identification.
AB  - It has recently been shown that it is possible to discriminate accurately among
      myoelectric signals underlying different muscle contraction types, specifically
      elbow flexion and extension and forearm pronation and supination. It was reported
      that once a number of distinctive features had been extracted from the
      myoelectric signals, a neural network could be trained to distinguish the
      contraction types with an impressively high accuracy. In the present paper, we
      show that a technique known as parallel cascade identification can be used to
      construct classifiers that can also accurately differentiate the contraction
      types. The use of parallel cascades has the benefit of dispensing with the need
      for feature extraction, so that raw myoelectric signal data can be used directly.
      In addition, very little data are required to train the parallel cascades to
      distinguish accurately novel incoming myoelectric signals. Results of using
      parallel cascades to distinguish forearm pronation, supination, and elbow flexion
      are presented.

PMID- 9236983
TI  - Technical features of a CCD video camera system to record cardiac fluorescence
      data.
AB  - A charge-coupled device (CCD) camera was used to acquire movies of transmembrane
      activity from thin slices of sheep ventricular epicardial muscle stained with a
      voltage-sensitive dye. Compared with photodiodes, CCDs have high spatial
      resolution, but low temporal resolution. Spatial resolution in our system ranged
      from 0.04 to 0.14 mm/pixel; the acquisition rate was 60, 120, or 240 frames/sec.
      Propagating waves were readily visualized after subtraction of a background
      image. The optical signal had an amplitude of 1 to 6 gray levels, with signal-to
      noise ratios between 1.5 and 4.4. Because CCD cameras integrate light over the
      frame interval, moving objects, including propagating waves, are blurred in the
      resulting movies. A computer model of such an integrating imaging system was
      developed to study the effects of blur, noise, filtering, and quantization on the
      ability to measure conduction velocity and action potential duration (APD). The
      model indicated that blurring, filtering, and quantization do not affect the
      ability to localize wave fronts in the optical data (i.e., no systematic error in
      determining spatial position), but noise does increase the uncertainty of the
      measurements. The model also showed that the low frame rates of the CCD camera
      introduced a systematic error in the calculation of APD: for cutoff levels > 50%,
      the APD was erroneously long. Both noise and quantization increased the
      uncertainty in the APD measurements. The optical measures of conduction velocity
      were not significantly different from those measured simultaneously with
      microelectrodes. Optical APDs, however, were longer than the electrically
      recorded APDs. This APD error could be reduced by using the 50% cutoff level and
      the fastest frame rate possible.

PMID- 9236984
TI  - Computer model of gastric electrical stimulation.
AB  - The aim of the study was to simulate gastric electrical stimulation using a
      computer model of gastric electrical activity and suggest a possible avenue
      toward reliable gastric pacing. Modeling was based on the conoidal dipole model
      of gastric electrical activity described earlier. It was assumed that local,
      nonpropagated contractions can be produced circumferentially using 4 rings of
      stimulating electrodes supplied with 2-sec phase-locked bipolar trains of 50 Hz,
      15 V (peak to peak) rectangular voltage. Temporal and propagation organizations
      of gastric electrical activity described in the conoidal dipole model were used
      to derive the geometry of the stimulating electrodes and the time shifts for
      phase-locking of the electrical stimuli applied to the different circumferential
      electrode sets. The major assumptions and findings of the model were tested on
      two unconscious dogs. The model produced completely controllable simulated
      gastric contractions that could be propagated distally by phase-locking the
      stimulating voltage. The values of interelectrode distances in different rings,
      as well as the distances between the successive rings, were also derived. The
      concept of invoked circumferential contractions that are artificially propagated
      by phase-locking the stimulating voltage could be an avenue toward reliable
      gastric pacing of gastroparetic patients.

PMID- 9236985
TI  - Compact and accurate linear and nonlinear autoregressive moving average model
      parameter estimation using laguerre functions.
AB  - A linear and nonlinear autoregressive moving average (ARMA) identification
      algorithm is developed for modeling time series data. The algorithm uses Laguerre
      expansion of kernals (LEK) to estimate Volterra-Wiener kernals. However, instead
      of estimating linear and nonlinear system dynamics via moving average models, as
      is the case for the Volterra-Wiener analysis, we propose an ARMA model-based
      approach. The proposed algorithm is essentially the same as LEK, but this
      algorithm is extended to include past values of the output as well. Thus, all of
      the advantages associated with using the Laguerre function remain with our
      algorithm; but, by extending the algorithm to the linear and nonlinear ARMA
      model, a significant reduction in the number of Laguerre functions can be made,
      compared with the Volterra-Wiener approach. This translates into a more compact
      system representation and makes the physiological interpretation of higher order
      kernels easier. Furthermore, simulation results show better performance of the
      proposed approach in estimating the system dynamics than LEK in certain cases,
      and it remains effective in the presence of significant additive measurement
      noise.

PMID- 9236986
TI  - Surface coverage effects on defibrillation impedance for transvenous electrodes.
AB  - Transvenous defibrillation electrodes are constructed by wrapping conductive
      elements around an insulating base. However, these conductive elements do not
      cover the entire area of the base. The effects of varying the surface area
      coverage on the defibrillation impedance (DZ) are unknown. To understand the
      effects, four transvenous right ventricular test leads were specially fabricated.
      A ring design was used with 3 mm diameter cylinders equally spaced along a 5 cm
      length, ending 11 mm from the pacing tip. Three leads consisted of 4, 8, and 15
      rings each of length approximately 2.4 mm so that the coverages were 20%, 40%,
      and 70%, respectively. The fourth lead used 8 rings of length approximately 1.2
      mm each and had a coverage of 20%. DZ for each lead was obtained using three
      methods: (i) computer simulation; (ii) in vitro measurement in a tank; and (iii)
      in vivo measurement in nine dogs during defibrillation testing. The DZs from
      either of the first two methods correlated very well (r = 0.98) with the mean DZs
      from the third method, indicating that in vivo DZs can be predicted from computer
      and in vitro models. The study shows that: (i) at the same ring length, DZ
      decreases as coverage (number of rings) increases; (ii) at the same coverage, DZ
      decreases as ring length decreases; and (iii) in vivo, a statistically
      significant difference was observed in DZ between the leads with 20% coverage and
      the leads with higher coverages. No statistically significant difference was
      observed between leads with coverages > 40%.

PMID- 9236987
TI  - Rupture of the perivisceral aorta: atherosclerotic versus mycotic aneurysm.
AB  - Twelve patients with rupture of the perivisceral abdominal aorta were admitted to
      the UCLA Medical Center between 1984 and 1996. Six patients had atherosclerotic
      thoracoabdominal aneurysms (TAA) which ruptured in the visceral segment of the
      aorta. The remaining 6 patients proved to have ruptured mycotic aneurysm (MA).
      Clinical presentation was different in the two groups. Whereas all 6 patients
      with TAA and < 24 hr history of abdominal, chest, or back pain, patients with MA
      had these symptoms for 2-5 weeks (mean 3.4 weeks). History of sepsis was present
      in 4/6 MA and in 0/6 TAA patients. No difference in risk factors for
      atherosclerosis were seen between these two groups. Clinical outcomes were also
      different. Operation consisted of in situ vascular grafting in all patients.
      Operative mortality for TAA was 33% (2/6), whereas all patients with MA survived
      repair with no operative mortality. Two patients had cardiac arrest prior to
      surgery. One of these had a TAA and died 5 days after surgery, whereas the other
      survived repair of an MA. Follow-up ranges from 1-84 months (mean 48 months).
      Four survivors in the TAA group are alive at 6, 8, 14, and 84 months, with the
      latter having a pseudoaneurysm of the visceral patch-graft anastomosis. All 6
      patients with MA are alive at 1-73 months (mean 39 months) without evidence of
      graft sepsis or recurrent aneurysm. We conclude that rupture of the visceral
      portion of the aorta is often associated with a mycotic process, with important
      differences noted in clinical presentation when compared to atherosclerotic TAA.
      Surgical intervention is effective in both MA and TAA. Operative mortality,
      however, is significantly higher in patients with ruptured TAA. In situ
      prosthetic replacement for ruptured MA is associated with low mortality and
      excellent long-term results.

PMID- 9236988
TI  - Ruptured visceral artery aneurysms.
AB  - Visceral artery aneurysms are uncommon lesions that are rarely identified in the
      absence of symptoms. Between February 1972 and April 1992, nine patients (5 men
      and 4 women) with rupture of visceral artery aneurysms were treated. The average
      age was 62 years old (range 39 to 86 years old). The arteries involved were the
      splenic (4), the common hepatic (2), the left hepatic (1), the celiac (1), and
      the superior mesenteric (SMA) (1). No ruptured renal artery aneurysm was
      identified. Six patients presented with abdominal distension, pain, and
      hemodynamic instability. Three patients had recurrent gastrointestinal bleeding
      with erosion into the duodenum, the common bile duct or the pancreatic duct. All
      three had unnecessary gastrointestinal operations despite preoperative (2
      patients) or intraoperative (1 patient) identification of a visceral artery
      aneurysm. One patient with an SMA aneurysm had ligation and bypass. Three
      patients with splenic artery aneurysms had splenectomy. The remaining five
      patients had either ligation or resection without arterial reconstruction. No end
      organ dysfunction was identified. There was one death (11%) due to the SMA
      aneurysm. Pathological findings in four patients were cystic medial necrosis,
      diffuse deficiency of the internal elastic lamina, fibromuscular dysplasia, and
      atherosclerosis, respectively. The remainder were thought to be due to
      atherosclerosis on gross examination. Rupture of visceral artery aneurysms occurs
      infrequently and can be treated by simple ligation in most cases. Recognition
      that rupture of splanchnic arterial aneurysms into adjacent viscera can cause
      recurrent gastrointestinal bleeding may prevent both substantial delays in
      diagnosis and inappropriate therapy.

PMID- 9236989
TI  - Diagnosis and management of patients with peripheral macroemboli from thoracic
      aortic pathology.
AB  - Transesophageal echocardiography (TEE) has improved the detection of thoracic
      aortic pathology and further elucidated its role as a source of peripheral
      arterial emboli. Since 1993 we have used TEE to evaluate the thoracic aorta in
      patients with peripheral emboli without identifiable cardiac sources. Five
      patients suffered a total of eight embolic events originating from thoracic
      aortic mural thrombus (TAMT). The four females and one male ranged in age from 56
      to 82 years. Emboli occurred to the upper extremities in four instances, lower
      extremities in three instances, and the visceral vessels in a single instance.
      Thromboembolectomy was performed in each case except for a patient who initially
      underwent aortobifemoral bypass. He was discovered to have TAMT after a
      subsequent embolic event. All patients were anticoagulated after TAMT was
      identified but in one case anticoagulants were discontinued after an
      intraabdominal hemorrhage. All patients are alive without limb loss while one
      patient has experienced recurrent embolization despite anticoagulation. TEE is a
      sensitive and useful diagnostic modality in patients with "cryptogenic" arterial
      embolization. Whether surgical management or anticoagulation for the primary
      lesion is optimal therapy remains a question. However, anticoagulation appears
      effective in this small experience.

PMID- 9236990
TI  - Deployment and healing of an ePTFE encapsulated stent endograft in the canine
      aorta.
AB  - This study evaluated deployment mechanics and long-term healing of an
      endoluminally placed stent/graft in normal canine aortas. The endoluminal graft
      (ELG) consisted of a 8.5 cm segment of expanded polytetrafluoroethylene (ePTFE)
      graft material (Impra, Inc., Tempe, AZ) encapsulating a series of six Palmaz P
      128 stents (Johnson & Johnson Interventional Incorporated, New Brunswick, NJ)
      along the length of the graft. The prostheses were deployed via the femoral
      artery using a 14Fr delivery system that contained a balloon catheter to expand
      the ELG in the infrarenal aorta. Twenty-one prostheses were deployed and
      evaluated at 1 week (n = 3), 1 month (n = 3), 3 months (n = 3), 6 months (n = 9),
      and 1 year (n = 3). Dimensions of the infrarenal aorta were determined with
      intravascular ultrasound (IVUS) and angiography prior to deployment of devices.
      Real-time fluoroscopy and IVUS were used to monitor device deployment with both
      imaging modalities repeated following implantation. Gross inspection and
      microscopic evaluation was performed on the explanted specimens following in vivo
      evaluation by CT scan, IVUS, and angiography prior to retrieval of the specimens.
      The prostheses were easily deployed from the femoral access site. Oversizing of
      the deployment balloon compared to the aortic diameter was necessary to
      accommodate the 10% device recoil observed following balloon deflation, however,
      all devices were seated against the aortic wall as evidenced by IVUS. At explant,
      all devices ware widely patent with limited luminal thrombosis observed in four
      specimens (19%). Devices were well-incorporated by cellular ingrowth into the
      ePTFE with the formation of neointima. No device migration or postdeployment
      recoil was observed. ePTFE graft material between stents protruded slightly into
      the vessel lumen accounting for a 10% luminal reduction. Fully supported ELG's
      consisting of balloon expandable stents encapsulated in ePTFE are easily deployed
      using a low-profile delivery system. Specimens demonstrated uniform long-term
      patency and healing up to 1 year in a canine aortic model. Those preliminary
      findings support further study of this fully supported prosthesis in the
      treatment of arterial disease.

PMID- 9236991
TI  - Diagnosis and management of arterial compression at the thoracic outlet.
AB  - Neurovascular compression syndromes at the thoracic outlet generally present with
      predominantly arterial, venous, or neurogenic symptoms. The arterial
      abnormalities produce unique problems in diagnosis and management, and usually
      affect young, otherwise healthy, active individuals. Between 1984 and 1995 23
      patients presented to our facility, with acute symptoms of arterial occlusion or
      embolization, found to be originating from the axillosubclavian arterial segment.
      The group comprised 14 females and nine males, ranging from 15 to 74 years, with
      an average age of 37 years. There were seven competitive athletes, three
      industrial workers, and 13 home, office, or service workers. The most severe
      presenting symptoms, occurring alone or in combination, and ranked in order of
      frequency observed, were: arm 'claudication' (74%), hand ischemia (48%), and
      digital gangrene (44%). Transaxillary thoracic outlet decompression was
      undertaken in 22 cases. This was combined with arterial reconstruction in 11
      cases and sympathectomy for ischemic causalgia in seven cases. Transaxillary
      resection of a cervical rib was accomplished in 8 cases. There was one
      postoperative graft occlusion (PTFE), corrected by thrombectomy, with cumulative
      secondary patency (to 64 months), and one secondary embolic occlusion. Excepting
      the two secondary procedures, no patient had recurrent symptoms at a mean follow
      up of 61 months. Effective and durable correction of the axillosubclavian
      arterial compressive abnormalities requires adequate thoracic outlet
      decompression, and anatomic vascular reconstruction when necessary. Failed prior
      procedures were a consequence of inaccurate diagnosis, failure to identify and
      correct the proximal embolizing arterial lesion, or inadequate decompression.
      Unilateral Raynaud's symptoms require meticulous investigation for arterial
      compression at the thoracic outlet with careful interpretation of subtle
      angiographic findings.

PMID- 9236992
TI  - Early benefits of subfascial endoscopic perforator surgery (SEPS) in healing
      venous ulcers.
AB  - Efficacy of subfascial endoscopic perforator vein surgery (SEPS) in assisting the
      healing of venous ulcers was determined. During the period June 1995 to May 1996,
      19 limbs in 17 patients were treated by SEPS. Thirteen limbs had open ulcers
      (class 6), five limbs had healed ulcers (class 5), and one limb had severe
      lipodermatosclerosis (class 4). There were nine male and eight female patients
      (average age 58, range 33-86). One male had bilateral open ulcers and one female
      had one open and one healed ulcer. Open ulcers had been present for an average
      duration of 4.4 years (range 1-14 years). The average ulcer size was 2.8 x 2.2 cm
      (range 1 x 1 cm to 12 x 6 cm). All operations were conducted on an outpatient
      basis. At surgery an attempt was made to correct all superficial venous
      pathophysiology. In addition to SEPS, 12 limbs (63%) had greater saphenous vein
      (GSV) stripping and 15 patients (79%) had stab avulsion of painful varicose
      veins. The average number of perforators ligated during SEPS was 3.68 (range 2
      8). All active ulcers healed within 90 days. The mean time to healing was 30.5
      days (range 6-90 days). Minor postoperative complications (one groin hematoma,
      three wound infections) occurred in four limbs (21%). There have been no ulcer
      recurrences during follow-up (mean 8.6 months, range 3-16 months). Outpatient
      SEPS is an important adjunct in the treatment of chronic venous insufficiency.
      Experience in this group of 19 limbs strongly suggests that SEPS appears to
      accelerate the healing of venous ulcers compared to historical controls.

PMID- 9236993
TI  - Asymptomatic carotid artery stenosis screening in patients with lower extremity
      atherosclerosis: a prospective study.
AB  - Eighty-nine male veterans presenting to a vascular surgery clinic with
      symptomatic lower extremity atherosclerosis were prospectively screened by duplex
      scan for asymptomatic carotid artery stenosis (CAS). Their chief complaint was:
      claudication (90%), rest pain (6%), and ischemic ulcer or gangrene (4%). The mean
      ankle-brachial index (ABI) was 0.77. Twenty-five CAS > 50% were detected in 18
      (20%) patients. Twelve CAS > 75% were detected in 11 (12%) patients. There was no
      difference between patients with and without CAS > 50% with regards to mean ABI,
      history of angina, diabetes, hypertension, prior coronary artery bypass, or
      history of smoking. Carotid bruit was associated with ipsilateral CAS > 50% [p <
      0.0001, sensitivity (52%), specificity (88%), positive predictive value (41%),
      negative predictive value (92%)]. As a result of the screening, eight elective
      carotid endarterectomies have been performed to date in six (7%) patients with
      one transient twelfth cranial nerve paresis as the only postoperative
      complication. We conclude that: (1) male patients presenting with symptomatic
      lower extremity atherosclerosis have a 20% prevalence of asymptomatic CAS > 50%,
      (2) there is no correlation between the degree of lower extremity ischemia and
      CAS > 50%, (3) carotid bruit is significantly associated with CAS > 50%, but has
      a low sensitivity, and (4) routine CAS screening should be considered for all
      male patients with symptomatic lower extremity atherosclerosis regardless of
      whether a bruit is present.

PMID- 9236994
TI  - Use of the in-situ lesser saphenous vein bypass from popliteal to peroneal
      artery.
AB  - Lesser saphenous vein grafts have become an important element in limb salvage
      surgery. Their location frequently dictates that the graft be translocated for
      use. This incurs the disadvantages of ischemia and increased manipulation of the
      graft and loses the advantages of an in-situ bypass. The use of the lesser
      saphenous vein as an in-situ graft for tibial artery reconstruction offers the
      advantages of reduced vein graft injury and improved patency. Technical
      requirements for an in-situ lesser saphenous bypass include that graft inflow be
      based on the popliteal artery, the vein length suffice to reach the target
      artery, and the runoff vessel have adequate size, length, and collateral
      connections to allow reasonable likelihood of success. The surgical approach
      requires the patient be in a prone position allowing a posterior longitudinal
      incision in the leg. Exposure of the distal portion of the peroneal artery is
      accomplished by separating the peroneus brevis and flexor hallucis longus. The
      peroneal artery is then visualized when the fibular attachments of the flexor
      hallucis longus are divided. Our experience indicates that the lesser saphenous
      vein may be successfully used as an in-situ conduit for bypass to the distal
      peroneal artery. Technical innovations such as flexible valvulotomes with
      detachable heads, and tourniquet control of bleeding facilitate the operation. A
      posterior approach to the popliteal and crural arteries affords the ability to
      use the lesser saphenous vein as an in-situ bypass.

PMID- 9236995
TI  - Late disruption of Dacron aortic grafts.
AB  - Aneurysmal degeneration, or complete disruption of Dacron grafts (as opposed to
      anastomotic complications such as pseudoaneurysms), are not expected by vascular
      surgeons. We have noted two such cases. A 65-year-old male who had an
      aortobifemoral, double-velour Dacron graft in 1980, presented in 1995 with a
      large, pulsatile mass in the right lower quadrant, caused by disruption of the
      mid-portion of the right limb of the Dacron graft. In a second case, a 68-year
      old man had a Dacron aortobifemoral graft placed in 1968 which developed diffuse
      aneurysmal defects, noted clinically in 1987. Both patients had successful graft
      replacement. A review of the literature indicates that this complication,
      although unusual, has been noted periodically. Between 1970 and 1996, we
      identified 11 case reports of aortic Dacron graft rupture, including knitted
      Dacron (4), double velour (3), woven (1), knitted thin wall (1), and unspecified
      Dacron grafts (2). An inquiry to the FDA disclosed another 68 cases of Dacron
      graft failure in addition to those reported in the surgical literature. We
      present these cases to alert vascular surgeons of the possibility of Dacron graft
      degeneration, as late as 19 years after implantation. Diagnosis of the
      complication is readily apparent by clinical examination and imaging studies,
      which display an aneurysm of the graft remote from the anastomoses.

PMID- 9236996
TI  - Venous interruption for pulmonary embolism: the illustrative case of Richard M.
      Nixon.
AB  - This politically prominent patient was seen in consultation on October 26, 1974
      because of chronic venous thrombosis and a recent pulmonary embolism. His
      problems had begun in 1965 when he developed venous thrombosis in the left leg
      after a length trip by air. His treatment had been sporadic and his compliance
      with treatment less than satisfactory. Because of detailed phlebography
      demonstrating (1) no clots in the veins of the right leg, (2) extensive loose
      lying clot filling the superficial, deep, and external iliac veins on the left,
      and (3) because of prior difficulties with patient compliance unilateral
      interruption of the left external iliac vein above the top of the clot was
      proposed. Despite some postoperative complications, the patient made a full
      recovery and lived 19 years on warfarin therapy before death from unrelated
      causes. He suffered no significant edema or other postphlebitic symptoms in the
      affected leg. The history of the use of venous interruption under these
      circumstances is reviewed to justify the operation that was performed.

PMID- 9236997
TI  - Proximal arterial dilatation developing after surgical closure of long-standing
      posttraumatic arteriovenous fistula.
AB  - Concomitant discovery of long-standing arteriovenous fistula (AVF) and proximal
      dilatation is commonplace whereas the disclosure of proximal arterial dilatation
      several years after closure of AVF is much more surprising and less often
      described. The goal of this study was to call attention to this late
      complication, to evaluate its prevalence, and to describe the mechanism and
      outcome after treatment. Six new observations were added to 11 cases already
      published in the literature. Most AVF were located in the popliteal or
      superficial femoral arteries. The mean duration of these AVF was 20 years and 7
      months. The mean delay between closure of AVF and the discovery of arterial
      dilatation was 9 years and 8 months. One patient required emergency operation for
      rupture. Another patient sustained embolism. All patients were treated by
      exclusion-bypass. Six years after operation for arterial dilatation, one patient
      had to be reoperated on for impending rupture of an aortic aneurysm. These facts
      lead us to advocate 1) closure of all AVF, even when iatrogenic, whenever present
      for 45 days or longer, 2) careful observation of all patients after operation for
      long-standing AVF, 3) operation on all patients with arterial dilatation
      secondary to AVF, and 4) life-long surveillance of the proximal arteries of these
      patients.

PMID- 9236998
TI  - Strategies to increase the use of autogenous arteriovenous fistula in end-stage
      renal disease.
AB  - The purpose of this retrospective study was to review our experience with a
      consecutive group of end-stage renal disease (ESRD) patients using simple
      strategies to increase the use of autogenous vascular access, and determine
      whether the current trend of using synthetic bridge-graft fistula (BGF) rather
      than autogenous arteriovenous fistula (AVF), could be reversed, despite an aging
      population and broadening criteria for hemodialysis. All patients for vascular
      access surgery had careful preoperative clinical examination of the arm veins
      with outflow occlusion to determine the venous anatomy and continuity. Where no
      veins were apparent or their continuity in doubt, selective preoperative
      venography was performed. Where veins were unsatisfactory for forearm AVF, new or
      modified surgical procedures to use both the basilic and cephalic veins in the
      upper arm were performed. Intraoperative angioscopy was used to monitor vein
      quality and surgical technique. Ninety-eight primary vascular access procedures
      were performed in 76 patients, 75 (76.5%) AVF (forearm, n = 41; upper arm, n =
      34) and 23 (23.5%) BGF. Forty-one of 76 (54%) had already had at least one
      previous access procedure prior to this study. More than one access procedure was
      needed in 16 patients. Preoperative venography was performed in 22 (22.4%) and
      intraoperative angioscopy in 45 (45.9%) of the 98 procedures. The number of
      revisions required to maintain patency was significantly higher for BGF (37
      revisions in 14/23) than AVF (16 revisions in 13/75) (p < 0.0001, Poisson test)
      with an annualized secondary revision rate of 1.168 for BGF and 0.173 for AVF (p
      < 0.0001, Poisson test). AVF had both longer primary (p = 0.0001, log rank test)
      and secondary patency (p = 0.038, log rank test) than BGF. AVF as the primary
      vascular access can be significantly increased and the current trend of using BGF
      reversed with the use of simple clinical strategies to evaluate the suitability
      of the arm veins for vascular access.

PMID- 9236999
TI  - The superficial femoral vein as arterial substitute in infections of the
      aortoiliac region.
AB  - In situ autogenous reconstruction is an alternative therapy for abdominal aortic
      prosthetic graft infection. We have used the superficial femoral vein (SFV) as an
      arterial substitute for proximal aortic anastomosis in seven patients. Six
      patients presented with aortic perigraft infections and one had a mycotic
      aneurysm of the infrarenal aorta with a primary aortoenteric fistula. There were
      no intraoperative but two postoperative deaths. During follow-up (mean: 19.8
      months), one patient died at 5 months unrelated to his preceding vascular
      procedures; the others were doing well with patient SFV grafts 6-36 months after
      autogenous aortoiliac reconstruction. The SFV is a valuable donor vessel for
      autogenous reconstruction in the management of aortoiliac prosthetic graft
      infection. We explain both perioperative deaths in our treatment group with
      respect to the extent of the underlying infection and the virulence of the
      causative organism.

PMID- 9237000
TI  - Spontaneous dissection of the celiac artery.
AB  - We describe a case of intestinal angina caused by spontaneous dissection of the
      celiac artery and thrombosis of the superior mesenteric artery. Spontaneous
      dissection of a visceral artery is an uncommon occurrence that is usually
      diagnosed after fatal hemorrhage or ischemia. The underlying mechanism is unclear
      but the frequent association with multiple arterial lesions suggests general
      arterial disease. In symptomatic forms, surgical reconstruction is mandatory, to
      treat the lesion and allow definitive histological diagnosis.

PMID- 9237001
TI  - Ruptured Salmonella mycotic aneurysm of the extracranial carotid artery.
AB  - Mycotic aneurysms of the extracranial carotid artery are rare and difficult to
      diagnose and can lead to significant medical morbidity. Treatment of these
      lesions requires expert surgical management and necessitates an assiduous search
      for an underlying source. We report a case of a ruptured mycotic aneurysm of the
      cervical carotid artery due to Salmonella infection successfully treated by wide
      excision and saphenous vein patch angioplasty.

PMID- 9237002
TI  - Acute upper extremity ischemia during concomitant use of ergotamine tartrate and
      ampicillin.
AB  - Individual hypersensitivity to the vasoconstrictor effects of ergotamine tartrate
      has been observed even at doses within recommended limits. Hypersensitivity can
      be induced by concomitant use with other drugs. The best-documented example of
      drug-induced hypersensitivity to ergotamine tartrate involves antibiotics of the
      macrolides class. The mechanism underlying this interaction appears to be
      interference with metabolism of ergotamine tartrate by the liver. In the present
      report we describe a case of upper extremity ischemia during concomitant use of
      ergotamine tartrate and ampicillin. The fact that the effect was not dose
      dependent, disappeared when administration of ampicillin was discontinued, and
      reappeared when administration of ampicillin was resumed suggests that the
      underlying mechanism in our patient was immunologic. Since immunologic
      hypersensitivity to the vasoconstrictor effects of ergotamine tartrate is
      unpredictable, great caution and close surveillance is advisable when ergotamine
      tartrate is used in association with other drugs.

PMID- 9237003
TI  - Published results of surgery for aortoiliac occlusive disease.

PMID- 9237004
TI  - Surgical treatment of thoracic outlet compression syndromes. II. Supraclavicular
      exploration and vascular reconstruction.
AB  - Supraclavicular exploration has become a widely utilized, versatile, and
      effective approach in the treatment of thoracic outlet compression syndromes. It
      is applicable to neurogenic, arterial, and venous form of TOS. Although certain
      aspects of the surgical anatomy are quite familiar to most vascular surgeons,
      considerable attention must be given to the details of this procedure to avoid
      inadequate decompression, serious injury, or predictable causes of recurrent
      compression. Supraclavicular exploration and its variations provide an excellent
      approach to the entire spectrum of problems encountered in patients with TOS, and
      in many centers it has superceded the transaxillary approach previously
      popularized for these disorders. Because supraclavicular exploration for TOS
      involves a number of unique technical considerations and because it is typically
      applied to a difficult clinical problem outside the routine experience of most
      vascular surgeons, it should be undertaken only with appropriate training and
      interest in the comprehensive management of patients with TOS.

PMID- 9237005
TI  - An evaluation of the relationship between 'atopic skin' and skin irritability in
      metalworker trainees.
AB  - Skin hyperirritability to irritants as well as atopy are considered to be
      predisposing factors for contact dermatitis. The aim of the study was to evaluate
      whether these predictive factors are independent or whether they are so closely
      related that one could possibly replace the other 205 metalworker trainees
      underwent skin examination for skin atopy, including standardized questionnaire,
      clinical examination of the skin and a series of skin irritability tests. These
      tests included measurements of transepidermal water loss (TEWL) before and after
      irritation with 3 different irritants: sodium lauryl sulfate (SLS),
      dimethylsulfoxide (DMSO) and sodium hydroxide (NaOH). The results of the linear
      regression analysis demonstrate that skin atopy is not associated with increased
      skin irritability, as assessed by the irritability testing methods presented.

PMID- 9237006
TI  - Acute irritant contact dermatitis: recovery time in man.
AB  - Our understanding of the details of the recovery time of acute irritant contact
      dermatitis (ICD) is limited. We examined skin reactivity to a model surfactant,
      sodium lauryl sulfate (SLS), on previous acute ICD and normal sites over time
      with visual grading and noninvasive instruments. Acute ICD was induced on the
      upper arms of 18 volunteers (aged 30 to 51 years) by occluded application of 1%
      SLS for 24 h. Previous ICD and normal sites were provoked by occluded application
      of 2% or 7.5% SLS 30 min daily 4 consecutive days. Skin reactivity was assessed
      daily by visual erythema scoring (VES), transepidermal water loss (TEWL), skin
      color reflectance (SCR) and electrical capacitance (EC). Skin function of
      previous ICD sites assessed by VES, TEWL, SCR, and EC did not normalize until 2
      weeks later; all parameters of previous ICD returned to normal after 3 weeks.
      While skin reactivity to 2% and 7.5% SLS showed no differences between previous
      ICD and normal sites at 4 weeks, differences of irritant reactivity especially
      7.5% SLS between previous ICD and normal sites were significant at 3 weeks post
      provocation. Our results demonstrate that irritation evaluated with irritant
      provocation was long-lasting, even though skin functional parameters assessed by
      various bioengineering instruments returned to normal. Complete recovery of skin
      function including irritability after acute ICD induced by 1% SLS was achieved
      approximately 4 weeks later. The date were generated with a model surfactant; it
      remains to be determined whether similar responses will be noted with chemicals
      of different physiochemical properties.

PMID- 9237007
TI  - Content and reactivity to product perfumes in fragrance mix positive and negative
      eczema patients. A study of perfumes used in toiletries and skin-care products.
AB  - The aim of the study was to investigate the elicitation potential of perfumes
      from 17 commonly sold lower-price cosmetic products. 8 of the perfumes were from
      stay-on cosmetics and 9 were from wash-off cosmetics. Each perfume was tested in
      500 consecutive eczema patients, who also were tested with the European standard
      patch test series. 4.2% reacted to 1 or more of the wash-off product perfumes and
      3.2% to 1 or more of the stay-on product perfumes. Concordant positive reactions
      between the fragrance mix and the product perfumes were found in 81.3% of
      positive reactions to the stay-on product perfumes and in 52.4% of the reactions
      to the wash-off product perfumes. Compared to the fragrance mix alone, only 1
      additional case of contact allergy to the product perfumes was detected by balsam
      of Peru. Chemical analysis revealed that between 1 and 5 of the chemically
      defined constituents of the fragrance mix were present in all of the product
      perfumes. Geraniol was found in 12 of the 17 perfumes and was most often
      detected. The concentration of the target fragrance materials ranged from 0.005%
      1.35 w/v%. It is concluded that the allergenic constituents of the fragrance mix
      are impossible to avoid if perfumed cosmetics are used. Furthermore, patients
      suspected of perfume allergy need to be tested with their own perfumed products,
      as far from all cases of perfume allergy are detected by the fragrance mix and/or
      balsam of Peru in the European standard patch test series.

PMID- 9237008
TI  - The efficacy of different moisturizers on barrier recovery in hairless mice
      evaluated by non-invasive bioengineering methods. A model to select the
      potentially most effective product.
AB  - Moisturizers (emollients) are used frequently on normal and diseased skin.
      However, only few studies have examined their effects in dynamic situations and
      in more clinically relevant settings. We evaluated the effect of 4 commonly used
      products in a hairless mice model after acute skin barrier perturbation with
      acetone. The efficacy was evaluated by measurement of the transepidermal water
      loss (TEWL) and electrical conductance at various time intervals during barrier
      repair. The test products were compared with acetone-treated air-exposed controls
      allowed to recover otherwise normally and with a known irritant product,
      chlorhexidine cream 1%. Locobase was the most effective product in correcting
      barrier function and significantly improved barrier function during early stages
      of barrier recovery (< 6 h) without interfering with late stages of barrier
      recovery (> 6 h). The irritant control product, chlorhexidine cream 1%, delayed
      barrier recovery in the late stages. The model makes it possible to evaluate the
      combined effects of exogenous and endogenous components on barrier repair and to
      select the potentially most effective products before performing more cumbersome
      and time-consuming field studies.

PMID- 9237009
TI  - Prevalence of gold contact hypersensitivity in the west of Scotland.
AB  - 373 patients attending for routine patch testing were tested with 0.5% and 0.05%
      gold sodium thiosulfate (GST). 8 (2.1%) patients had a positive patch test, and a
      further 4 (1.0%) patient reactions which were interpreted as irritant 2 out of 8
      patients with a positive patch test to GST suspected gold allergy prior to
      testing, and both of these patients reported that their eczema resolved if they
      avoided gold jewellery. This is the lowest prevalence of hypersensitivity to GST
      reported and suggests that gold contact allergy may not be as widespread as has
      been recently proposed.

PMID- 9237010
TI  - Allergic contact dermatitis from a boxwood recorder.

PMID- 9237011
TI  - Occupational allergic contact urticaria from fungal but not bacterial alpha
      amylase.

PMID- 9237013
TI  - Waitresses' itch?

PMID- 9237012
TI  - Contact dermatitis from chamomile tea.

PMID- 9237014
TI  - Acute generalized exanthematous pustulosis induced by nifuroxazide.

PMID- 9237015
TI  - Contact dermatitis from lichens.

PMID- 9237016
TI  - Contact urticaria from lupin.

PMID- 9237017
TI  - Double use tests for latex allergy.

PMID- 9237018
TI  - Allergic contact dermatitis from 2,7-dihydroxynaphthalene in hair dye.

PMID- 9237019
TI  - Urticaria caused by type IV sensitization to isothiazolinones.

PMID- 9237020
TI  - Role of activation-dependent platelet membrane glycoproteins in development of
      subacute occlusive coronary stent thrombosis.
AB  - BACKGROUND: Platelets have an important role in coronary thrombosis. METHODS: We
      studied 151 consecutive patients undergoing implantation of Palmaz-Schatz stents
      because of suboptimal results after coronary balloon angioplasty treated by
      intense anticoagulation. Surface exposure of the constitutively expressed
      glycoprotein complex IIb-IIIa (CD41), P-selectin (CD62P) and of the GPIIb-IIIa
      complex activated exposure (of ligand-induced binding site-1) were determined, in
      addition to platelet count and plasma fibrinogen, before and daily for 12 days
      after stenting in peripheral venous blood samples. RESULTS: Six of 151 patients
      (3.9%) developed subacute stent thrombosis within the first week after stenting.
      The relative risk of stent thrombosis was 18.5-fold for patients with enhanced
      GPIIb-IIIa surface expression (P < 0.003; 95% confidence interval 2.1 to 163.1)
      before stent placement. In the period after stenting, platelet activation
      occurred, with an increase in fibrinogen receptor activity and P-selectin
      degranulation above pre-stent values (P < 0.01). In logistic regression analysis,
      GPIIb-IIIa before stenting emerged as a risk factor for stent thrombosis,
      independent of the activational status of platelets, platelet count or fibrinogen
      levels (P < 0.02). However, after stenting, P-selectin surface expression
      acquired prognostic importance for stent thrombosis (P < 0.05). CONCLUSION: We
      conclude that changes in platelet membrane glycoproteins are of prognostic value
      in predicting subacute stent thrombosis.

PMID- 9237021
TI  - Increased low-density lipoprotein peroxidation in elderly men.
AB  - BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) appears to
      play a pivotal role in atherogenesis. The specific role played by LDL
      peroxidation in aging is not known. Since estrogens may protect LDL from
      peroxidation in vitro and in vivo, we chose to investigate only men of various
      ages. OBJECTIVE: To determine whether LDL from healthy elderly men was
      differently susceptible to peroxidation than LDL of young and adult men. SUBJECTS
      AND METHODS: LDL was isolated from 15 normolipidemic young (aged 19-23 years), 17
      adult (aged 35-55 years), and 16 elderly (aged 77-90 years) healthy men. None of
      the men included in the study was a smoker or a hypertensive. LDL peroxidation
      was achieved by exposure to 5 mumol/l copper sulfate for 18 h at 37 degrees C,
      and some markers of lipid peroxidation (estimating various levels of
      peroxidation) were evaluated. RESULTS: The levels of lipid peroxides in LDL from
      our elderly men were already higher under basal conditions than were those both
      of adult and of young men. LDL from elderly men was more susceptible to
      peroxidation than was that of adult and young men. Furthermore, the lag time
      correlated inversely to age (r = -0.68, P < 0.01), whereas lipid peroxide and
      malonyldialdehyde levels correlated highly to age (r = 0.79 and r = 0.77, P <
      0.0002 and P < 0.0012, respectively). With aging the vitamin E content in LDL
      decreased whereas the arachidonic fatty acid content increased. More importantly,
      the relationship between the vitamin E content and the lag time made evident the
      parallel increase in lag time and in vitamin E level with aging. The vitamin E
      concentration also correlated inversely to levels of thiobarbituric acid-reactive
      substances in LDL from elderly patients (r = -0.61, P < 0.05). CONCLUSIONS: The
      present study shows that LDL peroxidation increases with age. This phenomenon may
      favor the progression of atherosclerosis in elderly men.

PMID- 9237022
TI  - Angiotensin converting enzyme gene polymorphism and the risk and extent of
      ischemic heart disease among Turkish patients.
AB  - OBJECTIVE: To evaluate the effects of the angiotensin converting enzyme gene
      polymorphism on the presence and extent of coronary artery disease and myocardial
      infarction among Turkish patients. METHODS: In total 393 consecutive patients
      undergoing coronary angiography were evaluated for cardiac risk factors including
      the lipoprotein profile, lipoprotein (a), apoprotein B, and apoprotein A1 levels.
      The angiotensin converting enzyme genotype was determined by polymerase chain
      reaction. The extent of coronary atherosclerosis was determined from the
      angiograms using the Gensini and Leaman scores. RESULTS: The angiotensin
      converting enzyme genotype was found not to be associated either with coronary
      artery disease (odds ratio 0.81, P > 0.05) or with myocardial infarction (odds
      ratio 1.16, P > 0.05). Exclusion of high-risk individuals failed to reveal any
      association for these subgroups. Furthermore, there was no association between
      aneurysm formation and the genotype (P > 0.05). The lipid parameters were also
      not affected by the genotype (P > 0.05). However, the extent of coronary
      atherosclerosis determined by the Gensini score was related significantly to the
      genotype by multivariate analysis (P = 0.007). CONCLUSION: The DD genotype is not
      associated with coronary artery disease and myocardial infarction among these
      angiographically assessed Turkish patients, even when low-risk subgroups are
      analysed. Nonetheless, the extent of coronary atherosclerosis in patients with
      coronary artery disease is affected by their genotype.

PMID- 9237023
TI  - Altered plasma levels of cytokines in patients with ischemic heart disease.
AB  - BACKGROUND: Cytokines play an important role in mediating inflammatory
      proliferative responses, including atherosclerosis. Alterations in the plasma
      levels of cytokines in patients with ischemic heart disease (IHD) remain to be
      examined. OBJECTIVE: To examine the possible alterations in the plasma levels of
      cytokines in patients with IHD and in controls. METHODS: Thirty-one patients with
      IHD and 16 controls were studied. The cytokines measured in our study included
      interleukin-6, macrophage-colony-stimulating factor (MCSF), transforming growth
      factor-beta (TGF-beta), and seven other major cytokines. The measurements were
      performed by using an enzyme-linked immunosorbent assay method. RESULTS: The MCSF
      levels were significantly higher in patients with IHD than they were in controls
      (P < 0.01), whereas the TGF-beta levels were significantly lower in patients with
      IHD than they were in controls (P < 0.01). Moreover, the levels of MCSF and those
      of TGF-beta were correlated negatively (P < 0.05). The interleukin-6 levels
      tended to be higher in patients with unstable angina. The plasma levels of other
      cytokines were below the detection levels in most cases. CONCLUSIONS: Results
      from studies in vitro suggested that the process of atherosclerosis is
      accelerated and inhibited by MCSF and TGF-beta, respectively. The present results
      thus suggest that the alterations in the plasma levels of MCSF and TGF-beta may
      be involved in the pathogenesis of IHD in humans.

PMID- 9237024
TI  - Peroxynitrite, the product of nitric oxide and superoxide, causes myocardial
      injury in the isolated perfused rat heart.
AB  - BACKGROUND: Recent studies have determined that the product of NO and superoxide
      is peroxynitrite (ONOO-), an anion with deleterious tissue-oxidant effects.
      OBJECTIVE: To examine the effects of ONOO- on the isolated perfused rat heart.
      Sprague-Dawley rat hearts were perfused with a cell-free, Krebs-Henseleit
      solution on a Langendorf perfusion apparatus. The hearts were subjected to 30 min
      infusions of vehicle (control); 10 mumol/l S-nitroso-N-acetylpenicillamine
      (SNAP), an NO donor; 10 mumol/l pyrogallol, a superoxide generator); 10 mumol/l
      SNAP plus 10 mumol/l pyrogallol, a mixture that generates peroxynitrite; or 10
      mumol/l SNAP plus 10 mumol/l pyrogallol plus 300 U/ml superoxide dismutase.
      RESULTS: SNAP or pyrogallol alone had no effect on cardiac function at the
      concentration used; however, infusion of the combination of SNAP and pyrogallol
      resulted in significant decreases in left ventricular developed pressure (to 83
      +/- 4%, P < 0.01, versus vehicle) and dp/dtmax (to 76 +/- 6.2%, P < 0.01, versus
      vehicle), and also resulted in a significant increase in production of lactic
      dehydrogenase (to 118 +/- 4%, P < 0.01, versus vehicle). The administration of
      superoxide dismutase with SNAP and pyrogallol reversed these deleterious effects.
      CONCLUSION: These results suggest that the formation of peroxynitrite
      significantly enhances the toxicities of .NO and O2.- and causes marked cardiac
      injury.

PMID- 9237025
TI  - Time-dependent increases in syndecan-1 and fibroglycan messenger RNA expression
      in the infarct zone after experimentally induced myocardial infarction in rats.
AB  - BACKGROUND: Syndecan-1 and fibroglycan, heparan sulphate proteoglycans, play
      important roles in extracellular matrix formation via their biological functions.
      OBJECTIVE: To examine experimentally the sequential changes in syndecan-1 and
      fibroglycan messenger RNA (mRNA) expression after acute myocardial infarction.
      MATERIALS AND METHODS: The left coronary arteries of male Sprague-Dawley rats
      were ligated and the hearts were excised on days 1-14, 28 and 42. Syndecan-1 and
      fibroglycan mRNA expression in the infarct and non-infarct zones and in sham
      operated hearts was determined by reverse transcriptase-polymerase chain
      reaction. Amplified products were quantified by densitometry of the
      electrophoresed bands stained with ethidium bromide and standardized relative to
      the glyceraldehyde 3-phosphate dehydrogenase or beta-actin mRNA expression.
      Northern hybridization was also performed in the infarct and non-infarct zones on
      day 3. RESULTS: Expression both of syndecan-1 and of fibroglycan mRNA began to
      increase on day 2. The expression attained maximum levels on day 3. The maximum
      levels of syndecan-1 and fibroglycan expression were, respectively, sevenfold and
      fivefold the preligation level and the level in the sham-operated hearts. The
      levels remained elevated until day 14, whereupon they declined gradually,
      returning to the control levels by around day 42. Northern blotting also
      demonstrated that there was an increased expression both of syndecan-1 and of
      fibroglycan mRNA in the infarct compared with that in the non-infarct zone on day
      3. CONCLUSION: Our results demonstrated that there are sequential increases in
      the expression both of syndecan-1 and of fibroglycan mRNA in the infarct zone
      after experimentally induced myocardial infarction in rats, suggesting that these
      proteoglycans play some role in the pathological course of infarction.

PMID- 9237026
TI  - Phenotypic modification of arterial smooth muscle cells in response to medial
      dissection.
AB  - BACKGROUND: In the treatment of peripheral arteries, percutaneous transluminal
      angioplasty is commonly associated with intimal tears and dissections. OBJECTIVE:
      To investigate the influence of medial dissection on the remodelling of the
      vessel wall after balloon injury. METHODS: Aortae were obtained from 14 Fauve de
      Bourgogne rabbits that had been fed a normal diet. Seven days after the initial
      pull-back injury, the aortae were examined using morphometric and
      immunocytochemical methods. RESULTS: Eight rabbits (57%) had a tear that extended
      into the media. Morphometric measurements showed that the intima was
      significantly thinner when there was a medial dissection [(18.3 +/- 6.9) x 10(-3)
      versus (39.1 +/- 3.5) x 10(-3) mm without dissection, P < 0.001]. In the media of
      injured vessels, medial dissection was associated with a greater accumulation of
      extracellular matrix proteins (50.5 +/- 9.7 versus 12.4 +/- 2.2% of the surface
      area), a marked reduction in alpha-smooth muscle actin content (36.6 +/- 5.4
      versus 47.4 +/- 7.5% of the surface area), a higher expression of a smooth muscle
      activation antigen (21.2 +/- 5.7 versus 8.9 +/- 1.5% of the 2P1A2-immunostained
      surface area) and an increase in the number of medial proliferating cell nuclear
      antigen-positive nuclei (8.2 versus 1.2% of labelled nuclei). CONCLUSION: These
      observations indicated that mechanical injury of the arterial wall induces a
      phenotypic activation of medial smooth muscle cells. In the case of acute
      distension, the response of the smooth muscle cells in the media was mainly
      responsible for wound healing in the presence of medial dissection; moreover,
      acute distension induced a significant higher state of activation and a medial
      repairing that could prevent migration towards the intimal space.

PMID- 9237027
TI  - Evaluation of patients with diabetes mellitus for coronary artery disease using
      dobutamine stress echocardiography.
AB  - BACKGROUND: There is a high prevalence of coronary artery disease (CAD) in
      patients with diabetes mellitus. Detection of inducible ischaemia using treadmill
      exercise testing may be limited by the relatively poor inherent predictive
      accuracy of the test. The purpose of this study was to determine the value of
      dobutamine stress echocardiography (DSE) for the detection of CAD in patients
      with diabetes mellitus. METHODS: Patients with diabetes mellitus referred for
      cardiac assessment were considered eligible for study. DSE was performed in a
      standard fashion. Significant CAD was defined as a > 50% luminal diameter
      stenosis on coronary angiography. RESULTS: A total of 52 patients (mean age 59
      years) with diabetes mellitus were studied prospectively using DSE. Risk factors
      for CAD included hypertension in 19, family history in 21, hypercholesterolaemia
      in 14, history of smoking in 38. The sensitivity, specificity, positive and
      negative predictive values of DSE for detection of CAD were 82, 54, 84 and 50%
      respectively. CONCLUSION: The specificity of DSE for CAD in patients with
      diabetes mellitus is low. Whether this reflects an underdetection of small vessel
      disease by contrast coronary angiography or whether it relates to test
      performance is unclear.

PMID- 9237028
TI  - Safety of dobutamine stress echocardiography in 474 consecutive studies.
AB  - BACKGROUND: With expanding applications and increasingly aggressive stress
      protocols, concerns about the safety of dobutamine stress echocardiography (DSE)
      have arisen. The purpose of this study was to analyse prospectively the safety,
      adverse event profile and complication rate of DSE. METHODS: Prospective data
      were recorded in a consecutive series of 474 patients undergoing DSE. Dobutamine
      was administered intravenously in graded infusion, each stage over 3 min, at 10,
      20, 40 and, if required, 50 micrograms/kg/min. Atropine (1 mg) was administered
      thereafter if the response remained suboptimal. RESULTS: The mean dose of
      dobutamine was 42 micrograms/kg/min, with 111 patients (23%) receiving 50
      micrograms/kg/min. Atropine was required for 27 patients (6%). No patient died or
      suffered a myocardial infarction. Sustained ventricular tachycardia occurred in
      one patient, angina pectoris in 127 (27%), non-sustained ventricular tachycardia
      in eight (2%) and supraventricular tachycardia in 19 (4%). Profound bradycardia
      requiring cessation of the test occurred in one patient. Pulmonary oedema
      developed in one patient. A hypotensive response requiring cessation of the test
      was seen in one patient. Test termination because the patient complained of
      nausea, tremor or headache was not required. CONCLUSION: DSE is safe. Side
      effects are rare and when they occur, are usually minor. Ischaemic pain is
      effectively treated by termination of the test and sublingual administration of
      nitrates.

PMID- 9237029
TI  - Left ventricular chamber stiffness from model-based image processing of
      transmitral Doppler E-waves.
AB  - BACKGROUND: Model-based image processing (MBIP) of Doppler E-waves eliminates the
      need for digitizing waveforms by hand or determining the contour 'by eye'. Little
      et al. (Circulation 1995, 92:1933-1939) used pressure-volume measurements for
      dogs to verify the physiologic-model-derived prediction that the left ventricular
      chamber stiffness, KLV1 can be determined from the deceleration time tdec, when
      that portion of the E-wave contour is fit by a cosine function. MBIP of clinical
      Doppler E-wave images to determine chamber stiffness KLV has not been performed.
      OBJECTIVE: We sought to determine KLV by MBIP of clinical Doppler E-wave images
      and elucidate the physiologic meaning of the harmonic oscillator filling model's
      parameter k. METHODS AND RESULTS: The unique mathematical relationship between
      the kinematic, harmonic oscillator model of filling and KLV predicts that the
      oscillator's spring constant k be linearly proportional to the chamber stiffness
      KLV. To verify this, digitally acquired, clinical Doppler transmitral flow
      velocity images from 21 subjects were analyzed. The parameter k and the stiffness
      KLV were computed independently for each subject and compared. In accordance with
      prediction, a linear relationship between k and the stiffness KLV, namely k =
      1.16 [A/(rho L)]KLV+41, r = 0.96, was observed. CONCLUSIONS: The oscillator
      parameter k is linearly proportional to the left ventricular chamber stiffness
      KLV. The MBIP approach allows automated computation of k and KLV, provides a
      robust, automated, observer independent method of Doppler transmitral flow
      velocity analysis, and eliminates the need for visual determination of the
      contour or measurement of its attributes by eye. It provides a stimulus for
      further validation of the relationships among K, KLV, and catheterization-based
      diastolic chamber properties in humans and their correlations with selected
      diastolic function-altering syndromes.

PMID- 9237030
TI  - High-dose diltiazem prevents migration and proliferation of vascular smooth
      muscle cells in various in-vitro models of human coronary restenosis.
AB  - BACKGROUND: Restenosis after coronary angioplasty is considered to be caused
      mainly by increased migration and proliferation of smooth muscle cells (SMC). The
      concept of local, site-specific delivery of pharmacologic therapies has opened
      the door for new, high-dose drug regimes. METHODS AND RESULTS: SMC were isolated
      by enzymatic disaggregation with collagenase/elastase from human coronary plaque
      tissue of 29 patients (pSMC) and post mortem from the coronary media of 33
      corpses (mSMC). Endothelial cells were isolated from human umbilical veins by
      enzymatic disaggregation with collagenase/dispase. By positive reaction with
      antibodies against smooth muscle alpha-actin and von Willebrand factor cells were
      identified as SMC or endothelial cells. In proliferation studies 5-150
      micrograms/ml diltiazem was added to the culture media of pSMC, mSMC and
      endothelial cells. After 5 days there was a significant dose-dependent inhibition
      of cell proliferation (for pSMC with > 50 micrograms/ml, for mSMC with > 25
      micrograms/ml, and for endothelial cells with > 5 micrograms/ml). In migration
      studies the effect of 5-150 micrograms/ml diltiazem on the velocity of migration
      of pSMC was investigated over a period of 48 h. Administration of diltiazem at
      concentrations of 100 and 150 micrograms/ml caused a significant inhibition of
      the migration of pSMC. The cytoskeletal components smooth muscle alpha-actin,
      vimentin, and alpha-tubulin of pSMC and the expression of von Willebrand factor
      of endothelial cells were investigated after an incubation period of 5 days with
      50 and 150 micrograms/ml diltiazem. In the transfilter coculture model the effect
      of 50 micrograms/ml diltiazem on mSMC was investigated after mechanical injury of
      cocultured endothelial cells. Administration of diltiazem at a concentration of
      50 micrograms/ml inhibited the development of a neointimal proliferate in the
      transfilter coculture model significantly (P < 0.001). CONCLUSIONS: A high dose
      of diltiazem inhibited the migratory and proliferative activities of coronary SMC
      significantly. In further experimental studies the effect of locally applied high
      doses of diltiazem on postangioplasty restenosis should be elucidated.

PMID- 9237031
TI  - Long-term results of coronary artery surgery.
AB  - The management of coronary artery disease is constantly being refined and, as a
      consequence, the long-term results of coronary artery surgery are under intense
      and continuous scrutiny. An appreciation of the long-term results of different
      surgical strategies in selected subgroups of patients with ischaemic heart
      disease is important in deciding which is the most appropriate treatment option
      between surgery, angioplasty, and continued medical treatment. It also permits
      the patient to make an informed choice when that choice may influence the
      treatment. Interventional cardiology is encroaching onto traditionally surgical
      territory, and what effect these changes have on long-term results remains to be
      seen. Operative management continues to improve, and the use of arterial conduits
      may have a survival advantage; however, attention to the secondary prevention of
      cardiac risk factors will have the most influence on the long-term results of
      surgery. A clearer understanding of the importance of risk-factor management, in
      particular lipid reduction by drug treatment, will improve the long-term results
      for patients undergoing operations, probably both in late mortality and in
      clinical events, including the need for further intervention.

PMID- 9237032
TI  - Molecular and cell biology of native coronary and vein-graft atherosclerosis:
      regulation of plaque stability and vessel-wall remodelling by growth factors and
      cell-extracellular matrix interactions.
AB  - Atherosclerotic plaque instability underlies unstable angina, myocardial
      infarction, and vein-graft occlusion. Whether in native coronary arteries or
      arterial grafts, atherosclerotic plaque stability is determined by proliferation
      and migration of vascular smooth muscle cells, accompanied by the deposition of
      new extracellular matrices. Necrosis or apoptosis of vascular smooth muscle cells
      has an additional influence on the final composition and tensile strength of the
      plaque. In vein grafts, intimal thickening is a precursor and predisposing factor
      for subsequent atherosclerosis. Understanding the regulation of vascular smooth
      muscle cells is thus a prerequisite for designing rational therapies; Recent
      insights are summarized and unresolved questions highlighted in this review. The
      role of interactions between growth factors and extracellular matrix components
      as positive and negative regulators is emphasized.

PMID- 9237033
TI  - How good is the radial artery as a bypass graft?
AB  - The radial artery is being used with increasing frequency to replace the
      saphenous vein as a coronary artery bypass graft, on the basis of the belief that
      it will provide improved long-term patency. Innovative techniques in assessing
      the ulnar collateral circulation to the hand continue to evolve, giving comfort
      to the surgeon. Several centres have confirmed that the early results of surgery
      using the radial artery are similar to those using conventional grafts. Few late
      graft patency results or clinical data have been reported. Unresolved issues,
      such as the importance of pathological changes in the radial artery, the
      prevention of spasm, and the hypoperfusion syndrome, lurk in the background. The
      role of the radial artery continues to evolve.

PMID- 9237034
TI  - Early release after cardiac surgery.
AB  - Early release after cardiac surgery can be facilitated by the implementation of a
      standard protocol for pre- and postoperative care. This protocol involves
      aggressive pharmacological therapy, in combination with education and support.
      Accelerated recovery and release is inherently attractive because the duration of
      intensive care unit stay and of total hospital stay are the most important
      determinants of costs. However, in addition to the desire for reduced costs, the
      patients must be clearly seen to benefit from earlier rehabilitation and release.
      Retrospective studies have shown no significant differences in mortality or
      morbidity between patients who have received conventional care and those given
      'fast-tracked' care after cardiac surgery, and follow-up surveys have shown a
      high level of patient satisfaction with the care. Some centres report that all
      cardiac surgery patients are now fast-tracked.

PMID- 9237035
TI  - Bibliography current world literature.

PMID- 9237036
TI  - Immunosenescence revisited. Does it have any clinical significance?
AB  - Immunosenescence refers to the influence of aging on the immune system. Numerous
      problems are encountered in studying this topic, the main one being the influence
      of concomitant disease. Despite the great efforts that have been devoted to
      research in this field, the results of studies performed to date have not been
      convincing and, until now, no sound scientific evidence has emerged to show that
      immunosenescence is clinically significant. The only possible exceptions to this
      are the discovery of a selective defect in cell-mediated immunity and the
      reactivation of varicella zoster virus. Therefore, many more, and better
      designed, studies will have to be conducted before the full clinical impact of
      immunosenescence can be delineated.

PMID- 9237037
TI  - Principles of antibiotic prescribing in the elderly.
AB  - Clinicians providing care to elderly patients must appreciate the subtle clinical
      manifestations that herald the onset of life-threatening infectious disease. Aged
      patients with an infection may have neither fever nor leucocytosis, making
      diagnosis challenging. Often, the early features of infectious disease are
      nonspecific and may resemble inflammatory or neoplastic processes, or there may
      be insufficient time to await definitive laboratory confirmation, and empirical
      antimicrobial treatment must be initiated. Aging involves inevitable deleterious
      alterations in biological processes and, in many elderly patients, this is most
      strongly characterised by diminished renal functional capacity. This has a major
      influence on antimicrobial prescribing in the elderly, because therapeutic
      efficacy must be achieved while minimising the risk of drug-related toxicity.
      Before prescribing an antibiotic to an aged patient with an infection, the
      clinician must be cognisant of the patient's drug allergy history and the other
      drugs that the patient is taking. Ignorance of potential drug-drug interactions
      can result in ineffective treatment or enhanced toxicity. The therapy of elderly
      patients with infections is being expanded. To reduce costs and enhance the
      efficiency of care, systems have been developed to provide antimicrobial care in
      the home and in long term care facilities. Home healthcare has burgeoned, and
      drugs that are well tolerated, have a broad spectrum of activity and are simple
      to administer (e.g. ceftriaxone and fluoroquinolones) appear to be eminently
      suitable for this therapeutic role. Physicians must also be informed of the
      factors responsible for the emergence of resistant bacteria that are contributing
      to infections in institutional and community settings. Clinicians should strive
      to curb inappropriate antibiotic use to stem the tide of infections that are
      caused by multidrug-resistant bacteria.

PMID- 9237038
TI  - Drug selection for optimal treatment of hypertension in the elderly.
AB  - Progressive aging of the world's population means that choosing the most
      effective drugs for the elderly is becoming increasingly important. The treatment
      of hypertension in the elderly is complicated because of the need to consider
      altered pharmacokinetics, comorbidity and multiple drug therapy in these
      patients. Antihypertensive treatment in the elderly has important and documented
      beneficial effects. However, no single drug class is suitable as the first-choice
      therapy for all elderly patients. The most appropriate choice of an
      antihypertensive drug often depends on comparative adverse effect profiles and
      the presence of comorbid disease.

PMID- 9237040
TI  - Age-related changes in male gonadal function. Implications for therapy.
AB  - In contrast with women, who experience a complete and abrupt cessation of ovarian
      function during the menopause, aging men largely maintain their testicular
      androgen production. Nevertheless, most cross-sectional studies indicate that
      there is a partial decrease in testosterone levels with aging, although this has
      not been confirmed by other studies. The disparity among studies stems from
      differences in study design, patient numbers, assay techniques and inclusion
      criteria. Proposed mechanisms for an age-associated decline in testosterone
      production include: (i) defects in the hypothalamic-pituitary-testicular axis;
      (ii) an increase in sex hormone binding globulin levels; (iii) environmental
      factors; (iv) medication use; and (v) chronic illness. The potential beneficial
      effects of testosterone replacement therapy in hypogonadal men include increased
      bone density, increased muscle strength, an improved feeling of well-being and an
      improved metabolic profile. These benefits need to be weighted against the
      potential risks of androgen therapy, such as erythrocytosis, sleep apnoea, and
      the stimulation of benign prostatic hypertrophy or an occult prostate malignancy.
      Consequently, androgen replacement should be used with caution in elderly men
      with hypogonadism until the results of well-controlled prospective studies are
      available.

PMID- 9237042
TI  - Gene regulation by mechanical forces.
AB  - Endothelial cells are subjected to various mechanical forces in vivo from the
      flow of blood across the luminal surface of the blood vessel. The purpose of this
      review was to examine the data available on how these mechanical forces, in
      particular cyclic strain, affect the expression and regulation of endothelial
      cell function. Studies from various investigators using models of cyclic strain
      in vitro have shown that various vasoactive mediators such as nitric oxide and
      prostacyclin are induced by the effect of mechanical deformation, and that the
      expression of these mediators may be regulated at the transcription level by
      mechanical forces. There also seems to be emerging evidence that endothelial
      cells may also act as mechanotransducers, whereby the transmission of external
      forces induces various cytoskeletal changes and second messenger cascades.
      Furthermore, it seems these forces may act on specific response elements of
      promoter genes.

PMID- 9237041
TI  - Oral idarubicin. A review of its pharmacological properties and clinical efficacy
      in the treatment of haematological malignancies and advanced breast cancer.
AB  - Idarubicin is an anthracycline agent available as both oral and intravenous
      formulations. The oral formulation has demonstrated efficacy in the treatment of
      advanced breast cancer, low-grade non-Hodgkin's lymphoma, myelodysplastic
      syndromes and as first-line induction therapy of acute myelogenous leukaemia
      where intravenous anthracycline treatment is precluded. It also has potential in
      ameliorating blast crisis of chronic myelogenous leukaemia and in multiple
      myeloma. The most frequent adverse effects associated with oral idarubicin are
      those commonly found with anthracyclines, namely myelosuppression, nausea and
      vomiting, diarrhoea and mucositis. There appears to be minimal significant
      cardiotoxicity with oral idarubicia. In summary; available data concerning oral
      idarubicin in haematological malignancies and advanced breast cancer are
      sufficiently encouraging to warrant further research. To maximise the use of oral
      idarubicin, future studies should define the optimal dose for elderly patients,
      its comparative efficacy with other available regimens and address quality-of
      life and pharmacoeconomic issues associated with the substitution of oral for
      intravenous chemotherapy.

PMID- 9237043
TI  - Regulation of c-jun gene expression in endothelial cells by the protein kinase
      inhibitor staurosporine.
AB  - The proto-oncogene c-jun, a member of the family of immediate-early genes, is
      transcriptionally induced in different cell types by a variety of stimuli,
      including mitogens, tumor promoters, growth factors. We show here that the
      protein kinase inhibitor staurosporine, which inhibits both the serine-threonine
      and tyrosine specific protein kinases, also causes differential regulation of the
      c-jun gene in endothelial cells. Increasing concentrations of staurosporine
      modulated the steady-state levels of c-jun mRNA in bovine aortic endothelial
      (BAE) cells in a multiphasic manner. The half-life of c-jun mRNA did not change
      significantly under these conditions, suggesting that the modulations in the mRNA
      levels were caused primarily by differential transcriptional activity of the
      gene. The expression of c-jun gene is believed to be regulated by its own
      product, the JUN protein, which constitutes a major component of the inducible
      transcription factor AP-1. In order to test whether the differential regulation
      of c-jun gene was caused by the differential activation (or inactivation) of the
      AP-1 transcription factor, the DNA-binding activity of this transcription factor
      in staurosporine-treated cells was measured. Gelshift analysis with a synthetic
      oligonucleotide probe showed modest effects of staurosporine on the DNA-binding
      activity of the transcription factor AP-1. The changes observed in the DNA
      binding activity of AP-1 did not parallel the changes observed in the steady
      state levels of c-jun mRNA. Similarly, the expression of an AP-1 dependent
      reporter gene construct was regulated in a fashion entirely different from the c
      jun gene during the same protein kinase inhibitory conditions. These results
      suggest the existence of an alternative pathway that regulates the c-jun gene
      expression in endothelial cells independent of both the protein kinase and AP-1
      transcription factor activation steps.

PMID- 9237045
TI  - Circulating endothelin-1 in obstructive sleep apnea.
AB  - Endothelin (ET)-1 is a potent vasoconstrictive and mitogenic peptide produced by
      endothelial cells and degraded predominantly in pulmonary vasculature. We
      measured ET-1 in 9-normotensive and 14 hypertensive men with obstructive sleep
      apnea. The ET-1 levels were higher in both normotensive (mean +/- SD, 6.3 +/- 2.8
      pg/ml) and hypertensive (7.8 +/- 3.0 pg/ml) groups than in 66 healthy controls
      (2.9 +/- 1.2 pg/ml). Ten patients were restudied after three months of nCPAP
      treatment. No decrease in ET-1 was observed.

PMID- 9237044
TI  - Enhancement of membrane fluidity in cholesterol-poor endothelial cells pre
      treated with simvastatin.
AB  - We examined the membrane fluidity of the cholesterol-poor bovine carotid artery
      endothelial cells (BAEC). Cholesterol-poor BAEC were obtained by treating the
      cells with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      under 10% low density lipoprotein (LDL)-deficient serum condition for 2 days.
      Simvastatin reduced the intracellular cholesterol content significantly at a
      concentration of 0.1 microgram/ml. The reduction in the cholesterol content was
      accompanied by the enhancement of the cell membrane fluidity which was measured
      by a photobleaching technique. Additional data suggested that the reduction in
      cholesterol content referred to the reduction in the proliferation of BAEC.

PMID- 9237046
TI  - Neurovascular [125I]-ET-1 binding sites on human peripheral nerve.
AB  - [125I]-ET-1 binding to human peripheral nerve was studied using a combination of
      in vitro autoradiography and immunohistochemistry. Dense binding was
      predominantly to ETA receptors located on smooth muscles cells of the neural
      microvessels and the perineurium. These results identify regions where locally
      released ET-1 may affect neural vascular perfusion and play a pathophysiological
      role in certain conditions, such as diabetic neuropathy.

PMID- 9237039
TI  - Drug-induced syndrome of inappropriate antidiuretic hormone secretion. Causes,
      diagnosis and management.
AB  - Hyponatraemia is common among the elderly, and may be caused by physiological
      changes, disease processes or drugs. About half of elderly patients with
      hyponatraemia have features typical of the syndrome of inappropriate antidiuretic
      hormone secretion (SIADH). It is important to establish whether drugs are the
      cause, as this is easily remediable. The clinical manifestations of SIADH are
      predominantly attributable to hyponatraemia and serum hypo-osmolality. The
      severity of the signs and symptoms depends on the degree of hyponatraemia and the
      rapidity with which the syndrome develops. Although a growing number of drugs
      have been reported to produce SIADH, most published reports concern vasopressin
      and its analogues, thiazide and thiazide-like diuretics, chlorpropamide,
      carbamazepine, antipsychotics, antidepressants and nonsteroidal anti-inflammatory
      drugs. Old age is a risk factor for SIADH following the use of many of these
      drugs. The use of these drugs in combination, excessive fluid intake and other
      underlying conditions that limit free water excretion increase the risk. Drug
      induced SIADH usually resolves following cessation of the offending agent(s).
      Additional measures are required in patients with symptomatic hyponatraemia,
      including fluid restriction and intravenous sodium chloride and/or furosemide
      (frusemide) therapy. Careful monitoring is essential, with particular attention
      paid to the rate and extent of correction of the hyponatraemia.

PMID- 9237047
TI  - Transcytosis of albumin in endothelial cells is brefeldin A--independent.
AB  - To determine whether in endothelial cells (EC) the pathways of endocytosis and
      transcytosis of macromolecules interconnect, the effect of Brefeldin A (BFA) on
      these processes was tested. To this purpose EC were grown to confluence on
      plastic culture dishes or on cell culture chamber inserts placed into
      corresponding wells, so as to obtain a dual chamber system. The cells maintained
      the typical characteristics of EC and had an electrical resistance in the range
      of 30-60 Ohm.cm2. Transendothelial transport of albumin conjugated to the
      fluorochrom Texas Red (Alb-TR) and of horseradish peroxidase (HRP) added to the
      upper compartment, in the absence or presence of BFA (0-25 micrograms/ml), was
      evaluated in aliquots collected from the lower compartment. At different time
      intervals, quantitative data were obtained by fluorimetry and spectrophotometry.
      In other experiments transcytosis of Alb-TR was examined in the presence of 100
      microM forskolin (an inhibitor of BFA effect). The endocytosis of Alb-TR and HRP
      was evaluated by incubating EC with the probes, and the internalized tracers
      determined in the cell lysate using the methods described above. The results
      showed that BFA has no significant effect on transcytosis of albumin and HRP. In
      contradistinction, BFA (5 micrograms/ml) reduced markedly endocytosis of HRP (by
      47%). Forskolin has no effect on transcytosis. The data indicate that the BFA
      induced perturbance in the endocytic route does not affect the transcytotic
      pathway of albumin, and suggest that in EC, transcytosis of macromolecules may
      represent a shortcut for rapid and direct transport of some plasma molecules
      across the cell.

PMID- 9237048
TI  - Deactivation mechanism of platelets.

PMID- 9237049
TI  - Felbamate and meprobamate: a comparison of their anticonvulsant properties.
AB  - The anticonvulsant effect of felbamate and meprobamate were compared in a series
      of models for seizure activity and regarding their neurotoxic action. In the MES
      test, felbamate was active below neurotoxic doses. Meprobamate had an ED50 in the
      range of neurotoxic doses. The s.c. PTZ test was influenced by meprobamate in a
      fairly low dosage (ED50 66 mg/kg), but for felbamate no clearly dose-related
      effect could be shown up to 150 mg/kg. Reflex epilepsy in gerbils was stronger
      suppressed by meprobamate (ED50 34 mg/kg) than by felbamate (ED50 63 mg/kg). In
      amygdala kindled rats, meprobamate proved to be the most active compound, both
      regarding treatment of fully kindled rats, development of kindling and
      independent discharges from a mirror focus (secondary epileptogenesis), which
      were fully suppressed by oral treatment with 80 mg/kg for 30 days. Both drugs
      were weakly effective in a model for absence epilepsy in rats. The unexpectedly
      high activity of meprobamate justifies a second look at the anticonvulsant
      properties of the drug, especially since it was extensively used as an anxiolytic
      drug in the past with few obvious serious side effects.

PMID- 9237050
TI  - The Neurotoxicity Scale--II. Results of a patient-based scale assessing
      neurotoxicity in patients with epilepsy.
AB  - The Neurotoxicity Scale was devised as a patient-based report scale to assess the
      adverse effects of antiepileptic drugs on cognitive function. In a previous
      report we reported the clinical validity of the scale, tested in a double-blind
      randomized study, using a benzodiazepine in normal volunteers. In the present
      study, the clinical sensitivity, construct validity and reliability of the scale
      was tested in patients with epilepsy. Patients (n = 189), selected from both
      participating centres, representative for the patients with chronic epilepsy were
      included in the study. Reliability was tested with Cronbachs alpha and yields an
      almost maximal score (.95). Clinical sensitivity was compared with the previous
      normal volunteer study and was evaluated as satisfactory. Construct validity
      showed a five-factor structure, explaining 66.5% of the variance, with 'fatigue
      and slowing' as the dominant factor. In line with the assumptions for this scale
      and with the results obtained in normal volunteers, the scale appears to be
      unsuitable for differential assessment of type or severity of drug-induced
      impairment. The most valid primary outcome measure is the overall score that
      renders a global ('all or nothing') evaluation indicating that a subject
      experiences cognitive impairment and associates this with the antiepileptic
      treatment. Other factors that may impair cognitive function, such as seizure
      frequency do not influence this score. The scale has therefore maximal
      applicability as a screening instrument in outpatient practice and in early
      (phase II, IIIa) drug trials.

PMID- 9237051
TI  - Neurochemical actions of gabapentin in mouse brain.
AB  - Gabapentin (GBP) is a recently licensed antiepileptic, drug whose mode of action
      remains to be fully elucidated. The following studies were designed to
      investigate the effects of GBP on several gamma-aminobutyric acid (GABA) related
      neurochemical parameters in mouse brain. GBP (0-75 mg/kg) was administered by
      intraperitoneal injection either as a single dose or twice daily for 8 days.
      Animals were sacrificed 4 h after the final administration and their brains
      removed and analysed for concentrations of GABA, glutamate and glutamine and the
      activities of GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD).
      Single dose GBP increased brain GABA-T activity and glutamine concentration but
      was without effect on GAD activity or the concentrations of GABA and glutamate.
      Following repeated treatment with GBP, brain GABA-T activity was consistently
      decreased and there was also a decrease in brain glutamate concentration.
      Repeated drug treatment was without effect on the activity of GAD or on the
      concentrations of GABA and glutamine. These results suggest that GBP has effects
      on the GABAergic system which may contribute to its antiepileptic and/or
      neuroprotective actions.

PMID- 9237052
TI  - Decreased density of lymphocyte benzodiazepine receptors in drug-resistant
      epileptic patients.
AB  - Peripheral benzodiazepine receptors (PBR) may have a role in epilepsy and in
      mediating antiepileptic drug effects. Since PBR in blood mononuclear cells may be
      acted on by anticonvulsant drugs, we investigated possible modifications of these
      receptors in newly diagnosed patients, before and after antiepileptic treatment
      and in drug-resistant epileptic patients. A significantly lower receptor density,
      with no difference in affinity, was observed in drug-resistant patients, compared
      to newly diagnosed patients and to normal age-related controls. We suggest the
      possible use of PBR as a peripheral marker of drug response.

PMID- 9237053
TI  - Effects of felbamate, gabapentin and lamotrigine on seizure parameters and
      excitability in the rat hippocampus.
AB  - The effects of three new antiepileptic drugs (felbamate, lamotrigine and
      gabapentin) on the parameters of seizure initiation and termination in one model
      of reverberatory seizures in the hippocampal-parahippocampal loop in urethane
      anesthetized rats were determined. All three of the drugs caused a dose-dependent
      decrease in the duration of the seizure discharge. Only very high doses of
      felbamate had a significant effect on seizure initiation. In addition to the
      seizure model, we tested the three new anti-epileptic drugs for an effect on
      excitability, on paired-pulse inhibition and on long-term potentiation (LTP) in
      the dentate gyrus of the urethane-anesthetized rat. None of the drugs altered LTP
      or excitability. However, gabapentin altered paired-pulse inhibition, causing a
      loss of inhibition. For felbamate and lamotrigine, the effects of seizure
      duration are consistent with their clinical effects as antiepileptic drugs.
      However, the effect of gabapentin on paired-pulse inhibition suggests a
      proconvulsant effect and the effect on seizure duration suggests an antiepileptic
      effect.

PMID- 9237054
TI  - A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in
      adults with previously untreated epilepsy.
AB  - In the last 5 years oxcarbazepine (OXC) has been registered in many countries for
      use as first-line and add-on treatment for partial seizures with or without
      secondarily generalized seizures (PS) and generalized tonic-clonic seizures
      without partial onset (GTCS). Its use as monotherapy in adults with newly
      diagnosed epilepsy was investigated in this double-blind, randomized, parallel
      group comparison with phenytoin (PHT). A total of 287 adult patients, with either
      PS or GTCS, were randomized. After retrospective baseline assessment, patients
      were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase
      was divided into two periods: a flexible titration period of 8 weeks, followed by
      48 weeks of maintenance treatment. In the efficacy analyses, no statistically
      significant differences were found between the treatment groups. Seventy patients
      (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during
      the maintenance period. A total of 56 of the patients in the OXC group
      discontinued treatment prematurely (five because of tolerability reasons)
      compared to 61 in the PHT group (16 for tolerability reasons). The number of
      premature discontinuations due to adverse experiences showed a statistically
      significant difference in favour of OXC. There was no statistically significant
      difference between the groups with respect to the total number of premature
      discontinuations. This trial provides further support for the efficacy and safety
      of OXC as first-line treatment in adults with PS and GTCS. In addition, the
      results show that OXC has significant advantages over PHT in terms of
      tolerability.

PMID- 9237055
TI  - A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in
      children and adolescents with epilepsy.
AB  - In many countries oxcarbazepine (OXC) has been registered for use as first-line
      and add-on treatment for patients with partial seizures with or without
      secondarily generalized seizures (PS) and generalized tonic-clonic seizures
      without partial onset (GTCS). Its use as monotherapy in children and adolescents
      with newly diagnosed epilepsy was investigated in this double-blind, randomized,
      parallel-group comparison with phenytoin (PHT). A total of 193 patients aged 5-18
      years with either PS or GTCS were enrolled. After a retrospective baseline
      assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double
      blind treatment phase comprised two periods: an 8-week flexible titration period;
      followed by 48 weeks maintenance treatment. In the efficacy analyses, there were
      no statistically significant differences between OXC and PHT. Forty-nine (61%)
      patients in the OXC group and 46 (60%) in the PHT group were seizure-free during
      the maintenance period. In total, 24 patients in the OXC group discontinued
      treatment prematurely (two for tolerability reasons) compared with 34 in the PHT
      group (14 for tolerability reasons). The number of premature discontinuations due
      to adverse experiences was statistically significantly lower in the OXC group
      than in the PHT group. Moreover, the odds of an individual discontinuing
      prematurely (regardless of reason) were almost twice as high in the PHT group.
      This trial provides further support for the efficacy and safety of OXC as first
      line treatment in children and adolescents with PS and GTCS. In addition, the
      results show that OXC in these patients has significant advantages over PHT in
      terms of tolerability and treatment retention.

PMID- 9237056
TI  - Prevention of colon cancer.

PMID- 9237058
TI  - Dietary assessments in the European prospective study of diet and cancer (EPIC).
AB  - Biomarkers of nutrition intake were used to validate the dietary assessments
      proposed for use in the European prospective study of diet and cancer (EPIC). In
      the UK validation studies, the accuracy of several tested methods was assessed
      with weighed food records and biomarkers, 24 h urine nitrogen, potassium and
      plasma carotenoids and vitamin C. Correlations between dietary nitrogen intake
      from weighed food records and 24 h urine excretion were high (0.78-0.87). The
      correlations between nitrogen from estimated food diaries and urinary nitrogen
      were r = 0.60-0.70. Correlations with other methods were lower, but improved by
      energy adjustment, using residuals for those nutrients correlated with total
      energy, such as nitrogen and potassium, but not for nutrients not correlated with
      energy intake--for example, beta-carotene. Hence, the correlation between urinary
      nitrogen and unadjusted nitrogen from a food frequency questionnaire (FFQ) was
      0.24 but improved with energy adjustment to 0.49. UK EPIC uses three methods
      (diary, improved FFQ and 24 h recall) to assess diet, with repeated measures from
      the food diary at 18 months and four years. Ninety-three percent of first food
      diaries are returned completed by participants. Results from 200 subjects
      randomly selected from the first 2,000 recruits suggest that differences between
      methods with improved FFQ design are less obvious than in the initial validation
      study. Results from the diary are more closely correlated with plasma carotenoids
      and vitamin C than other methods, although supplements of vitamin C are the main
      determinant of the magnitude of correlations. More detailed biomarker studies are
      in progress among EPIC participants.

PMID- 9237059
TI  - Dietary patterns in Europe--preliminary results of dietary habits in the EPIC
      Study. European Prospective Investigation on Cancer and Nutrition.

PMID- 9237057
TI  - Main hypotheses on diet and cancer investigated in the EPIC Study. European
      Prospective Investigation into Cancer and Nutrition.

PMID- 9237060
TI  - Environmental and familial risk factors in relation to the colorectal adenoma-
      carcinoma sequence: results of a case-control study in Burgundy (France).
AB  - A case-control study in the Cote-d'Or area (Burgundy, France) investigated the
      relationship between environmental and familial risk factors and the different
      steps of the adenoma-carcinoma sequence. Two adenoma groups (< 10 mm and > or =
      10 mm), a polyp-free control group, a colorectal cancer group and a general
      population control group were recruited. Tobacco was associated with the risk of
      adenomas, and alcohol with the risk of large adenomas. They proved to be
      independently related to large adenoma formation when compared with controls.
      There was no association with cancer risk. Refined cereals, delicatessen, offal
      and fats appear to be risk factors along the adenoma-carcinoma sequence. This
      data does not support an increased risk with high consumption of fresh meat, or a
      protective effect of dairy products and calcium. A high consumption of vegetables
      was a protective factor for cancer, mainly in men. Excess weight and body mass
      index influenced the earlier step of the adenoma carcinoma sequence and excess
      calorie intake was risk factor for cancer. The decision to study precancerous
      lesions as well as cancer appears fruitful. Results suggest that the three stages
      of large bowel carcinogenesis are partly related to diet in different ways. They
      are concordant with risk factors recorded for colorectal cancer, but suggest some
      local specificities.

PMID- 9237061
TI  - Chemoprevention of metachronous adenomas of the large bowel: design and interim
      results of a randomized trial of calcium and fibre. ECP Colon Group.
AB  - A European multicentric intervention study, led by the colon group of the
      European Cancer Prevention Organization, is under way. The main aim of the study
      is to test the efficacy of oral calcium supplementation with 2 g calcium per day
      and oral dietary supplementation with mucilaginous substances (as 3.8 g of
      ispaghula husk) on adenoma recurrence. Secondary aims are the study of treatment
      efficacy on colonic cell proliferation and on stool bile acid and sterol
      concentration. Serum and plasma samples are also collected. To better interpret
      the effect of the intervention, a diet history questionnaire and an aspirin and
      anti-inflammatory drug questionnaire are administered. The aim will be achieved
      through a randomized placebo-controlled clinical trial using a parallel design in
      patients aged 35 to 75 at entry with a complete colonoscopy and a clean colon.
      Overall, 655 subjects have been included. All randomized patients are followed up
      every six months for 3 years. If one of the evaluated interventions proves
      efficient, the benefits of a simple, safe and inexpensive prophylaxy for a very
      common cancer will be clear.

PMID- 9237062
TI  - Lifestyle factors including diet and cancer of the gallbladder and bile duct: a
      population-based case-control study in The Netherlands.

PMID- 9237063
TI  - Histamine-2-receptor antagonists and oesophageal cancer.
AB  - Peptic ulcer and gastrectomy are associated with an increased risk of oesophageal
      cancer. We considered the relation between treatment with histamine-2 (H-2)
      receptor antagonists and subsequent risk of oesophageal cancer. Data from a case
      control study conducted between 1984 and 1995 in northern Italy were used. These
      comprised 407 incident, histologically confirmed cases and 1168 controls admitted
      for acute, non-neoplastic, non-digestive tract conditions, unrelated to known
      risk factors for oesophageal cancer. Ten (2.5%) cases and 52 (4.5%) controls
      reported using H-2-receptor antagonists at some time, corresponding to a
      multivariate odds ratio (OR) of 0.5 (95% confidence interval 0.2-1.0). The OR was
      0.4 for subjects who had started use seven years earlier or less, and 0.6 for
      those who had started use more than seven years ago. These findings indicate that
      risk of oesophageal cancer is not increased among H-2-receptor antagonist users.
      This trend to protection may be explained in terms of chance alone, or may be
      partly related to a possible favourable impact of H-2-receptor-antagonists on
      chronic oesophageal carcinogenesis.

PMID- 9237064
TI  - Prior immunity-related medical conditions and oesophageal cancer risk: a
      population-based case-control study in Shanghai.
AB  - To investigate the role of immunity-related medical conditions in the aetiology
      of oesophageal cancer, data were analysed from a population-based case-control
      study, conducted in Shanghai during 1992-93. Information on histories of selected
      autoimmune diseases and allergic conditions was obtained from 163 incident cases
      of oesophageal cancer and 275 age- and sex-matched controls through personal
      interviews using a structured questionnaire. A significant 2.4-fold excess risk
      (95% CI, 1.3-4.4) of oesophageal cancer was associated with a history of
      autoimmune diseases after adjustment for age and sex. In contrast, a history of
      allergy was associated with a reduced risk (adjusted OR = 0.6, 95% CI = 0.4-0.9).
      The risk was also reduced 30-40% among individuals who reported having a moderate
      or strong skin reaction to mosquito bites. This study suggests that host immune
      function may be involved in the aetiology of oesophageal cancer. Further
      investigations into the mechanism of these observed associations are warranted.

PMID- 9237065
TI  - Double blind randomized trial on occult blood bead (OBB) and gastroscopy
      pathology screening for gastro-oesophageal cancer.
AB  - The study consists of two parts. In the first, 4,970 subjects were given the
      occult blood bead (OBB) test and 817 underwent gastroscopy: 40 of those screened
      were found to have cancer, 30 of which had early lesions (15 had carcinoma in
      situ). In the second part, a double blind randomized control study of the mass
      screening was conducted. All the tests were free of charge. Subjects over 30
      years of age were persuaded to participate. Two-hundred and eight people accepted
      the OBB test, gastroscopy and histopathological assessment. A total of four
      cancers (two early, one moderate and one advanced) were detected by OBB test. If
      the OBB is carried out properly, gastro-oesophageal cancer is unlikely to be
      missed. We believe that OBB gastroscopy screening for oesophageal and gastric
      cancer is reliable and practical.

PMID- 9237066
TI  - Latency periods in asbestos-related mesothelioma of the pleura.
AB  - Latency periods (time intervals elapsing between first exposure to asbestos and
      death) were examined in 421 cases of malignant pleural mesothelioma, diagnosed in
      the Trieste-Monfalcone area, Italy. Occupational data were collected from the
      patients or from their relatives by personal or telephone interviews. Routine
      lung sections were examined for asbestos bodies in 370 cases. Latency periods,
      calculated in 312 cases, ranged from 14 to 72 years (mean 48.7, median 51).
      Latency periods differed significantly from one occupational group to another.
      Mean latency periods were 29.6 among insulators, 35.4 among dock workers, 43.7 in
      a heterogeneous group defined as various, 46.4 in non-shipbuilding industry
      workers, 49.4 in shipyard workers, 51.7 among women with a history of domestic
      exposure to asbestos, and 56.2 in people employed in maritime trades. The ANOVA
      test indicated a correlation between latency periods and occupational groups.
      Latency periods in people with asbestos bodies visible in routine lung sections
      did not differ from those seen in cases with no evidence of asbestos bodies.
      These data suggest that intensity of exposure is a relevant, but not the only,
      factor in determining the duration of latency periods.

PMID- 9237067
TI  - Non-neoplastic changes in gastric antrum: are they different in distally located
      intestinal and diffuse-type gastric adenocarcinoma?
AB  - A total of 126 cases of primary adenocarcinoma of distal (antrum and/or adjacent
      body) stomach were reviewed. These cases were collected from the histopathology
      laboratory of Asir Central Hospital, Southwestern Saudi Arabia over an 8 year
      period (1987-94). Only gastrectomy specimens with non-neoplastic antral mucosa
      available for histological examination were included. Of 126 cases, 85 (67.5%)
      were of the intestinal type and 41 (32.5%) were of the diffuse type. Histological
      examination of the non-neoplastic antral mucosa showed: gastritis in 100% of
      these cases; Helicobacter pylori in 103/126 cases (81.8%); multifocal atrophic
      gastritis (MAG) in 53/126 cases (42.1%); intestinal metaplasia (IM) in 62/126
      (49.2%); and type III intestinal metaplasia in 30/62 cases (47.7%). None of these
      non-neoplastic changes of antral mucosa was significantly different when the
      prevalence of these changes in intestinal and diffuse type gastric adenocarcinoma
      were compared using the chi 2 test. The prevalence of these non-neoplastic
      lesions were calculated in a 126 dyspeptic age- and sex-matched control patients
      and were as follows: H. pylori 91%; gastritis 78%; MAG 7.4%; IM 19% and type III
      IM 1.6%. The prevalence of H. pylori bacilli and gastritis was not significantly
      different between the cancer patients and the controls. The prevalence of MAG, IM
      and type III IM was significantly higher among cancer patients compared with the
      control group.

PMID- 9237068
TI  - An epidemiological study of endometrial cancer, nutrition and health.

PMID- 9237069
TI  - Effect of fibre on bile acid metabolism by human faecal bacteria in batch and
      continuous culture.
AB  - The effect of various fibres on bile acid metabolism by human faecal bacteria was
      studied in batch and continuous culture models of the large intestine. The
      metabolism of the primary bile acids--chenodeoxycholic and cholic-was entirely
      oxidative in aerobic conditions, and the major metabolites were the 7-oxo
      derivatives of the parent bile acids. Addition of both undigested and digested
      wheat bran and pea fibre to aerobic batch cultures reduced metabolism in a dose
      dependent manner with undigested fibre being far more effective. In anaerobic
      conditions, the metabolism of primary bile acids was predominantly reductive: the
      major metabolites were the 7 alpha-dehydroxylated products of the parent bile
      acids--namely lithocholic acid (from chenodeoxycholic acid) and deoxycholic acid
      (from cholic acid), respectively. Addition of undigested crude fibre to batch
      cultures reduced 7 alpha-dehydroxylation in a dose-dependent manner; addition of
      digested crude fibre to anaerobic continuous cultures had no significant effect
      on bile acid metabolism. The soluble fibre lactulose needed to be added to reduce
      pH sufficiently (> or = 5.5), to prevent 7 alpha-dehydroxylation of primary bile
      acids. Reduction of 7 alpha-dehydroxylation was also associated with a
      substantial decrease in Bacteroides spp and a concomitant increase in
      Lactobacillus spp in the cultures. The failure of digested wheat bran to reduce
      bile acid metabolism in continuous culture is attributed mainly to the physical
      constraints of the systems which can handle no more than 4-6% particulate
      material due to blockage. It is concluded that anaerobic continuous culture
      systems with human faecal bacteria have some value as models of the human large
      intestinal environment, but further modifications are required before the effect
      of particulate fibres on the metabolism of bile acids can be fully addressed.

PMID- 9237070
TI  - Attributable risks for kidney cancer in northern Italy.
AB  - The percent population attributable risk (AR) for kidney cancer was estimated in
      relation to smoking habits, beta-carotene intake, history of cystitis and family
      history of kidney cancer, using data from a case-control study conducted between
      1985 and 1989 in Milan, northern Italy. The data comprised 133 histologically
      confirmed cases of incident kidney cancer and 392 controls, admitted to hospital
      for a wide range of acute, non-neoplastic, non-smoking-related diseases. On the
      basis of multivariate odds ratios (ORs), smoking habits accounted for about 26%
      of cases, a low beta-carotene intake for 18%, a history of cystitis for 7%, and a
      family history of kidney cancer in first-degree relatives for 3% of cases. Ever
      smoking and low beta-carotene intake combined explained 38% of all kidney
      cancers, and the combination of these two factors plus a history of cystitis and
      a family history of kidney cancer explained 45% of the incidence of the disease.
      Thus, even if available, dietary information was limited and the AR estimates
      were based on somewhat arbitrary assumptions. A considerable proportion of kidney
      cancers could be avoided simply by eliminating smoking and increasing consumption
      of fruit and vegetables in this Italian population. This would mean that about
      1,500 kidney cancer deaths every year in the whole of Italy could be avoided.

PMID- 9237071
TI  - NSAIDs, Barrett's oesophagus and adenocarcinoma prevention.

PMID- 9237072
TI  - ECP-EURONUT study of diet and intestinal metaplasia. ECP-EURONUT-IM Study Group.

PMID- 9237073
TI  - Second Strang International Cancer Conference: genetics and the environment New
      York, USA, 15-16 November 1996.

PMID- 9237074
TI  - Food fortification. Technology and quality control. FAO Technical Meeting.

PMID- 9237075
TI  - Residues of some veterinary drugs in animals and foods. Joint FAO/WHO Expert
      Committee on Food Additives.

PMID- 9237076
TI  - Biotechnology and food safety. Joint FAO/WHO Consultation. United Nations.

PMID- 9237077
TI  - Nutrition education for the public. FAO Expert Consultation. United Nations.

PMID- 9237078
TI  - Worldwide regulations for mycotoxins 1995. A compendium.

PMID- 9237079
TI  - The ovarian renin-angiotensin system in reproductive physiology.
AB  - The identification of the presence of prorenin, renin, angiotensinogen,
      angiotensin-converting enzyme, angiotensin II (Ang II), and Ang II receptors in
      the ovary suggests that there is a functional ovarian renin-angiotensin system
      (RAS). It could play a significant role in such areas of ovarian physiology as
      follicular development, steroidogenesis, oocyte maturation, ovulation, and
      follicle atresia. Expression of the ovarian RAS is regulated by gonadotropins.
      Ang II, a bioactive octapeptide of RAS, has important effects as a
      paracrine/autocrine regulator at different stages of the reproductive cycle. Ang
      II modulates ovarian steroidogenesis and formation of the corpus luteum and also
      stimulates oocyte maturation and ovulation via Ang II receptors on granulosa
      cells. In addition, increasing evidence demonstrates that Ang II is a major
      factor in regulating the function of atretic follicles. In any physiologic
      system, aberrations result in the development of pathologic states. Disturbances
      in the ovarian RAS can be the cause or the result of such reproductive disorders
      as polycystic ovary syndrome, ovarian hyperstimulation syndrome, ovarian tumors,
      and ectopic pregnancy. Data support the concept of an active and regulated RAS in
      ovarian follicles. Species differences observed in the expression of ovarian RAS
      suggest varying functional roles among species with respect to ovarian
      physiology.

PMID- 9237081
TI  - Neuroendocrine asymmetry.
AB  - The information available at present clearly indicates that asymmetry exists from
      the level of elementary particles to the human cerebral cortex, the latest stage
      of evolution. Cerebral lateralization is one of the well-known asymmetries. This
      paper summarizes the data published in the past decades on the asymmetry of the
      neuroendocrine system. The information on the sided-differences between the
      gonads, adrenals, and thyroid lobes and that on the lateralization of
      hypothalamic, limbic, and other brain structures participating in the control of
      the endocrine glands as well as relevant clinical observations are reviewed here.
      The innervation of the peripheral endocrine glands is also briefly summarized
      because the afferent and efferent fibers of these glands may represent one part
      of the pathway involved in neuroendocrine asymmetry. The data reviewed clearly
      indicate that some kind of asymmetry (morphological, biochemical, physiological,
      pathological) is evident at different levels of the neuroendocrine system (at
      limbic, hypothalamic, peripheral endocrine glands and their innervation) and
      there are species, sex, and age differences. Most of the information accumulated
      deals with the CNS-gonadal system. A majority of the observations suggest that in
      both male and female rats there is a predominance of the right half of brain
      structures controlling gonadal function. The asymmetry, however, is not
      restricted to CNS structures: it also exists at the level of the gonads,
      including their innervation. It appears that the characteristic pattern of the
      CNS-gonadal system becomes fixed only after sexual maturation. Very few reports
      are available suggesting some kind of asymmetry of the CNS-adrenal cortex and the
      CNS-thyroid system. There are convincing findings consistent with the view that
      in addition to the hypothalamo-adenohypophyseal system acting via the general
      circulation on the peripheral endocrine glands, there is also a pure neural link
      between the CNS and the gonads, the CNS and the adrenal gland, and also between
      the CNS and the thyroid. This link contains afferent and efferent pathways and is
      able to modulate the functional activity or the responsiveness of the gland. It
      may also serve as a neural reflex arc. It is assumed that the neuroendocrine
      asymmetry expresses itself through (i) hypophysiotrophic neurohormones and
      hormones of the peripheral endocrine glands, (ii) neural pathways, or (iii) a
      combination of (i) and (ii). The authors hope that this publication, in addition
      to providing an overview, will also stimulate research, both basic and clinical,
      in this exciting area of neuroendocrinology.

PMID- 9237080
TI  - The neuroendocrinology of thirst and salt appetite: visceral sensory signals and
      mechanisms of central integration.
AB  - This review examines recent advances in the study of the behavioral responses to
      deficits of body water and body sodium that in humans are accompanied by the
      sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by
      ingesting water and salty substances. These behavioral responses to losses of
      body fluids, together with reflex endocrine and neural responses, are critical
      for reestablishing homeostasis. Like their endocrine and neural counterparts,
      these behaviors are under the control of both excitatory and inhibitory
      influences arising from changes in osmolality, endocrine factors such as
      angiotensin and aldosterone, and neural signals from low and high pressure
      baroreceptors. The excitatory and inhibitory influences reaching the brain
      require the integrative capacity of a neural network which includes the
      structures of the lamina terminalis, the amygdala, the perifornical area, and the
      paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus
      (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the
      hindbrain. These regions are discussed in terms of their roles in receiving
      afferent sensory input and in processing information related to hydromineral
      balance. Osmoreceptors controlling thirst are located in systemic viscera and in
      central structures that lack the blood-brain barrier. Angiotensin and aldosterone
      act on and through structures of the lamina terminalis and the amygdala to
      stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and
      LPBN receive neural signals from baroreceptors and are responsible for inhibiting
      the ingestion of fluids under conditions of increased volume and pressure and for
      stimulating thirst under conditions of hypovolemia and hypotension. The interplay
      of multiple facilitory influences within the brain may take the form of
      interactions between descending angiotensinergic systems originating in the
      forebrain and ascending adrenergic systems emanating from the hindbrain. Oxytocin
      and serotonin are additional candidate neurochemicals with postulated inhibitory
      central actions and with essential roles in the overall integration of sensory
      input within the neural network devoted to maintaining hydromineral balance.

PMID- 9237082
TI  - Effects of food deprivation and a stressor on head pain.
AB  - This study sought to experimentally validate 2 self-reported trigger factors of
      headaches, namely negative affect (anxiety, depression, and anger) and hunger,
      and to investigate whether these triggers activated the same or different
      physiological mechanisms. Students (38 women and 18 men) who had suffered from
      frequent headaches (migraine or tension type) for 6 months or more were randomly
      assigned to 4 conditions, which involved manipulating hunger by means of 19 hr of
      food deprivation and negative affect by means of a stressor (difficult to solve
      anagrams). The findings were consistent with self-reports that hunger and
      negative affect can precipitate headaches in individuals who suffer from both
      migraine and tension-type headaches. The physiological responses to the
      experimental conditions differed, but the findings were not conclusive with
      respect to whether the trigger factors operated by means of a common biological
      pathway.

PMID- 9237083
TI  - Linking symptom-specific physiological reactivity to pain severity in chronic low
      back pain patients: a test of mediation and moderation models.
AB  - Symptom-specific reactivity to stress (lower paraspinal muscle reactivity) among
      chronic low back pain (CLBP) patients may exacerbate chronic pain. It was
      hypothesized that among CLBP patients (N = 107) only stress-induced lower
      paraspinal reactivity, and not reactivity in other indexes, would predict pain
      severity (PS), and that lower paraspinal reactivity would mediate or moderate
      links between depression and PS. Electromyogram readings from lower paraspinal
      and trapezius muscles, systolic and diastolic blood pressures, and heart rate
      were collected during mental arithmetic (MA) and an anger recall interview. The
      moderator hypothesis was supported: Only lower paraspinal reactivity during MA
      was related significantly to PS, but only among patients with high levels of
      depression. Thus, a profile of lower paraspinal hyperreactivity plus depressed
      affect may aggravate CLBP.

PMID- 9237084
TI  - Memory for pain and the delayed effects of distraction.
AB  - In spite of the popular belief that distraction is effective in coping with pain,
      there is evidence that a neutral distractor does not reduce people's reports of
      pain. However, it may be that distraction's effect is not detectable in immediate
      ratings, when the need to rate the pain forces the sufferer to concentrate on it.
      Instead, after a delay, when the pain itself is gone and the person must base the
      judgment on a memory of the event, having been distracted may attenuate the
      recalled pain. An experiment with 72 undergraduate participants tested this
      proposition, with 1 group highly distracted during cold-pressor pain and 1 group
      slightly distracted. Half of each group rated the pain immediately, and half
      waited 10 min after the event to rate the pain. The participants who gave
      immediate ratings showed no effect of distraction, but for participants who
      waited 10 min before giving their ratings, high distraction led to reduced
      reports of pain.

PMID- 9237085
TI  - Health effects of emotional disclosure in rheumatoid arthritis patients.
AB  - This study examined the effects of emotional disclosure of stressful events on
      the pain, physical and affective dysfunction, and joint condition of patients
      with rheumatoid arthritis (RA). Patients were randomly assigned to talk privately
      about stressful events (disclosure group, n = 36) or about trivial topics
      (control group, n = 36) for 4 consecutive days. Disclosure resulted in immediate
      increases in negative mood. At 2 weeks the 2 groups did not differ on any health
      measure, but at 3 months disclosure patients had less affective disturbance and
      better physical functioning in daily activities. There was no main effect of
      disclosure on pain or joint condition, but among the disclosure patients, those
      who experienced larger increases in negative mood after talking demonstrated
      improvements in the condition of their joints. This study concludes that, among
      RA patients, verbal disclosure and emotional processing of stressful life events
      induces an immediate negative mood followed by improved psychological
      functioning.

PMID- 9237086
TI  - Lymphocyte subset redistribution during acute laboratory stress in young adults:
      mediating effects of hemoconcentration.
AB  - Acute psychological stress is known to alter the distribution of circulating
      lymphocyte subsets and also to cause a reduction of plasma volume. Data were
      reanalyzed from 4 previously reported studies (E. A. Bachen et al., 1995; T. B.
      Herbert et al., 1994; A. L. Marsland, S. B. Manuck, T. V. Fazzari, C. J. Stewart,
      & B. S. Rabin, 1995; A. L. Marsland, S. B. Manuck, P. Wood, et al., 1995) to
      determine the extent to which changes in the concentration of lymphocyte subsets
      are attributable to such hemoconcentration. Meta-analytic procedures showed
      circulating concentrations of T-suppressor/cytotoxic (CD8) and natural killer
      (NK) cells to increase following acute laboratory challenge, whereas T-helper
      (CD4) and B- (CD19) cell populations did not change. Adjustments for concomitant
      hemoconcentration reduced the magnitude of stress-related increases in CD8 and NK
      cells significantly and revealed a decrease in CD4 and CD19 cell concentrations
      from baseline to stress measurements. These data provide evidence (a) that
      increases in circulating numbers of CD8 and NK cells following acute stress are
      partially attributable to hemoconcentration and (b) that CD4 and CD19 cell
      concentrations decrease during acute stress when hemoconcentration is taken into
      account.

PMID- 9237087
TI  - A natural experiment on the effects of ovarian hormones on cardiovascular risk
      factors and stress reactivity: bilateral salpingo oophorectomy versus
      hysterectomy only.
AB  - To test the effects of declining ovarian hormone levels on cardiovascular risk
      factors, blood pressure, lipids, weight, and physiological responses to stress
      were evaluated in 29 middle-aged premenopausal women prior to and following
      elective hysterectomy and/or bilateral salpingo oophorectomy (BSO). Prior to
      surgery, there were no group differences in standard or putative risk factors,
      with the exceptions of body composition measures and total cholesterol level.
      After surgery, women who had undergone BSO (n = 10) had higher levels of
      atherogenic lipids and stress-induced lipids and tended to have higher
      circulating levels of epinephrine and stress-induced systolic and diastolic blood
      pressure than women who had undergone hysterectomy only (n = 19). This study is
      consistent with the hypothesis that presence of ovarian hormones plays a key role
      in determining women's risk factor status.

PMID- 9237088
TI  - Attentional mediation of cigarette smoking's effect on anxiety.
AB  - It was hypothesized that smoking's calming effects are cognitively mediated and
      depend on the presence of a benign distractor, smoking narrows the focus of
      attention, thereby reducing anxiety by facilitating distraction from stressful
      cognitions (cf. C. M. Steele & R. A. Josephs's [1988] attention-allocation model
      of alcohol reinforcement). This notion was tested by examining the effect of
      smoking (vs. not smoking) on anxiety with and without a concurrent distraction in
      82 smokers; distraction effects were also assessed in 42 nonsmokers. As
      predicted, smoking reduced anxiety only when paired with a distractor. Further,
      these findings could not be explained by direct nicotine effects or nicotine
      withdrawal. Several measures of attention allocation failed to confirm the
      hypothesized cognitive mechanisms, however. Implications of the findings are
      discussed.

PMID- 9237089
TI  - Continued high-risk sex among HIV seropositive gay and bisexual men seeking HIV
      prevention services.
AB  - The authors examined HIV risk-related sexual behaviors in an ethnically diverse
      sample of HIV seropositive gay and bisexual men (N = 86). Measures of sexual
      behavior, substance use, condom attitudes, behavior change intentions, and
      engagement in risk-reducing practices were completed. Thirty-nine percent of the
      men reported engaging in unprotected anal intercourse in the past 3 months.
      Unprotected anal intercourse was associated with using nitrite inhalants, sex
      partners who used substances before sex, and low intentions to change risk
      behavior. These results highlight the difficulties that people living with HIV
      infection face in maintaining a lifetime of safer sex and the necessity of
      integrating clinical and prevention interventions for these persons.

PMID- 9237090
TI  - Effect of sexual motivation on men's risk perception for sexually transmitted
      disease: there must be 50 ways to justify a lover.
AB  - Recent research has incorporated situational factors into assessment of risk.
      Working from a rational appraisal framework, however, these studies have not
      emphasized contextual features that might introduce motivated risk assessment. In
      the current study, participants (N = 40 male undergraduates) lowered their risk
      perceptions for STDs following the induction of a sexual motivation. In an
      initial baseline condition, participants estimated the risk of contracting STDs
      from partners with relatively high- or low-risk sexual histories. In a subsequent
      trial, participants repeated the imagery task while viewing photographs that were
      high or low in sex appeal. As predicted, participants reduced their risk
      perceptions when they viewed photographs high in sex appeal. The only necessary
      precondition was the presence of nondiagnostic information from which they could
      construct biased risk estimates.

PMID- 9237091
TI  - Can we identify who will adhere to long-term physical activity? Signal detection
      methodology as a potential aid to clinical decision making.
AB  - Signal detection methodology was used to identify the best combination of
      predictors of long-term exercise adherence in 269 healthy, initially sedentary
      adults ages 50-65 years. Less educated individuals who were assigned to
      supervised home-based exercise of either higher or lower intensity and who were
      less stressed and less fit at baseline than other individuals had the greatest
      probability of successful adherence by the 2nd year. Overweight individuals
      assigned to a group-based exercise program were the least likely to be successful
      2 years later. Predictors of short-term (1-year) adherence were generally similar
      to predictors of 2-year adherence. Signal detection analysis may be useful for
      identifying subgroups of people at risk for underadherence who subsequently might
      be targeted for intervention.

PMID- 9237092
TI  - Effects of guided imagery and music (GIM) therapy on mood and cortisol in healthy
      adults.
AB  - Healthy adults (N = 28) participated in a randomized trial of Bonny Method of
      Guided Imagery and Music (GIM; a depth approach to music psychotherapy) sessions
      on mood and cortisol. Participants in both GIM and wait-list control conditions
      completed the Profile of Mood States (POMS) and donated 15 cc of blood before and
      after the 13-week intervention period and again at a 6-week follow-up. Split-plot
      factorial and post hoc analyses demonstrated that after 6 biweekly sessions GIM
      participants reported significant decreases between pre- and postsession
      depression, fatigue, and total mood disturbance and had significant decreases in
      cortisol level by follow-up. Pretest to follow-up decrease in cortisol was
      significantly associated with decrease in mood disturbance. A short series of GIM
      sessions may positively affect mood and reduce cortisol levels in healthy adults.
      Such changes in hormonal regulation may have health implications for chronically
      stressed people.

PMID- 9237093
TI  - State legislators' intentions to vote and subsequent votes on tobacco control
      legislation.
AB  - The predictive validity of state legislators' behavioral intentions in relation
      to their votes on tobacco control legislation was assessed by using the theory of
      planned behavior (I. Ajzen, 1991). Intentions to vote for cigarette tax increases
      were measured through interviews in the summer of 1994. A bill containing
      cigarette tax increases was considered about 8 months later. Votes were compared
      with intentions and were found to be consistent for 78% of these legislators (N =
      120). Multiple logistic regression analyses showed a strong independent
      relationship between intentions and voting and a similar effect of political
      party; results suggested but did not confirm that votes were predicted by
      interactions between intentions and perceived control. Legislator surveys that
      use this conceptual model can provide results relevant to understanding tobacco
      policy development.

PMID- 9237094
TI  - New protein engineering approaches to multivalent and bispecific antibody
      fragments.
AB  - Multivalency is one of the hallmarks of antibodies, by which enormous gains in
      functional affinity, and thereby improved performance in vivo and in a variety of
      in vitro assays are achieved. Improved in vivo targeting and more selective
      localization are another consequence of multivalency. We summarize recent
      progress in engineering multivalency from recombinant antibody fragments by using
      miniantibodies (scFv fragments linked with hinges and oligomerization domains),
      spontaneous scFv dimers with short linkers (diabodies), or chemically crosslinked
      antibody fragments. Directly related to this are efforts of bringing different
      binding sites together to create bispecific antibodies. For this purpose,
      chemically linked fragments, diabodies, scFv-scFv tandems and bispecific
      miniantibodies have been investigated. Progress in E. coli expression technology
      makes the amounts necessary for clinical studies now available for suitably
      engineered fragments. We foresee therapeutic advances from a modular, systematic
      approach to optimizing pharmacokinetics, stability and functional affinity, which
      should prove possible with the new recombinant molecular designs.

PMID- 9237095
TI  - The in vivo and in vitro characterisation of an engineered human antibody to E
      selectin.
AB  - BACKGROUND: E-selectin is an endothelial cell specific adhesion molecule that is
      believed to play an important role in the early stages of leukocyte
      extravasation. OBJECTIVES: Here we describe the construction and evaluation of an
      engineered human monoclonal antibody that blocks E-selectin function. RESULTS:
      SPLAT-1 is an engineered human monoclonal antibody that has a very similar
      affinity for E-selectin as its murine parent antibody. In vitro SPLAT-1 blocks
      the binding of human leukocytes to E-selectin and does not mediate antibody
      dependent cellular cytotoxicity (ADCC) or complement-mediated lysis of
      endothelial cells. In vivo, SPLAT-1 inhibits the recruitment of leukocytes to
      cytokine-inflamed human skin grafted on to SCID mice and has a long circulating
      half-life in primates. It does not appear to provoke an immune response in
      primates even on repeat administration. CONCLUSIONS: SPLAT-1 has the
      characteristics of a antibody suitable for human therapy studies.

PMID- 9237096
TI  - Biologically active human anti-crotoxin scFv isolated from a semi-synthetic phage
      library.
AB  - BACKGROUND: The display of repertoires of antibody fragments on the surface of
      filamentous bacteriophages offers a new way of making antibodies with predefined
      binding specificities. OBJECTIVES: Here we explored the use of this technology to
      find human antibodies with biological properties. Phage-scFv specific for
      crotoxin, the main toxic component of the venom of the South-American rattlesnake
      Crotalus durissus terrificus, were isolated from a 'single pot' repertoire of
      more than 10(8) clones made in vitro from human V gene segments [1]. The crotoxin
      molecule is composed of two noncovalently linked subunits: a basic and weakly
      toxic phospholipase A2 (PLA2) called component B (CB) and an acidic, nonenzymatic
      and nontoxic subunit called component A (CA). CA is able to increase the toxicity
      as well as the specificity of action of CB simultaneously reducing its enzymatic
      activity. STUDY DESIGN: Two clones were isolated (4-21 and 5-3-1) which are
      specific of the basic subunit CB, but of a moderate affinity (about 10(-7) M).
      Clones 4-21 and 5-3-1 have different amino acid sequences and different effects
      on CB properties suggesting that they are raised against different CB epitopes.
      Purely cholinergic synaptosomes isolated from Torpedo electric organs provide a
      suitable model to study the presynaptic effects of crotoxin. In this model, CB
      was shown to induce a larger acetylcholine release than crotoxin. RESULTS: A dose
      dependent increase of acetylcholine release was observed when crotoxin was
      incubated with increasing amounts of phage-scFv 4-21. This clone was also shown
      to increase the enzymatic activity of crotoxin. These observations suggest that
      phage-scFv might dissociate the complex CA-CB. It could be therefore a
      neutralizing antibody since CB is much less toxic than crotoxin. This shows that
      'single pot' libraries are capable of providing not only immunochemical reagents
      of high specificity but also biological reagents of high quality. The use of this
      library appears to open new possibilities for immune passive therapy.

PMID- 9237097
TI  - Cloning and cytotoxicity of a human pancreatic RNase immunofusion.
AB  - BACKGROUND: Immunotoxins based on plant and bacterial proteins are usually very
      immunogenic. Human ribonucleases could provide an alternative basis for the
      construction of less immunogenic reagents. Two members of the human RNase family,
      angiogenin and eosinophil-derived neurotoxin (EDN), have been fused to a single
      chain antibody against the transferrin receptor, which is known to be
      internalised by endocytosis. The fusion proteins proved to be very efficient
      inhibitors of protein synthesis using various cell lines. It is not yet known
      whether the side effects of angiogenin and EDN will compromise their potential
      use as immunotoxins. OBJECTIVES: The goal of this work was to construct a human
      immunotoxin with no harmful side effects. Bovine pancreatic ribonuclease has been
      shown to be as potent as ricin at abolishing protein synthesis on injection into
      oocytes. We therefore decided to clone its human analogue, which is fairly
      ubiquitous and per se non-toxic. An immunofusion of human pancreatic RNase with a
      single chain antibody against the transferrin receptor was tested for its ability
      to inhibit protein synthesis in three different human tumor cell lines. STUDY
      DESIGN: DNA coding for the human pancreatic RNase was cloned partially from a
      human fetal brain cDNA library and then completed by PCR using a human placental
      cDNA library as a template. The RNase gene was then fused with a DNA coding for
      an single chain antibody against the transferrin receptor (CD71). After
      expressing the fusion protein in E. coli, the gene product was isolated from
      inclusion bodies and tested for cytotoxicity. RESULTS: This fusion protein
      inhibited the protein synthesis of three human tumor cell lines derived from a
      melanoma, a renal carcinoma and a breast carcinoma, with IC50s of 8, 5 and 10 nM,
      respectively. These values were comparable with those using a similar fusion
      protein constructed with eosinophil derived neurotoxin (EDN) as the toxic moiety
      (IC50s of 8, 1.2 and 3 nM, respectively). The slightly lower activities of the
      human pancreatic RNase-scFv (pancRNase-scFv) with two of the cell lines suggests
      that fewer molecules are reaching the cytoplasmic compartment, since it was twice
      as active as EDN-scFv in inhibiting the protein synthesis of a rabbit
      reticulocyte lysate. CONCLUSION: These results demonstrate that the human
      pancreatic RNase, which is expected to have a very low immunogenic potential in
      humans with no inherent toxicity, may be a potent cytotoxin for tumor cells after
      antibody targeting.

PMID- 9237098
TI  - Enzyme immunoassays using bispecific diabodies.
AB  - BACKGROUND: Bispecific antibodies with a first binding specificity to a target
      antigen and a second to an enzyme have great potential in enzyme immunoassays. As
      bispecific antibodies are difficult to make, the use of recombinant bispecific
      antibody fragments may provide a breakthrough. OBJECTIVES: To make bispecific
      antibody fragments directed against an enzyme and to demonstrate their
      application in enzyme immunoassays. STUDY DESIGN: Bispecific antibody fragments
      were assembled as diabodies (Holliger P., Prospero T., Winter G. Proc. Natl.
      Acad. Sci. USA 90, 1993, 6444-6448) directed to an enzyme, E. coli beta
      galactosidase, and to each of three target antigens, hen-egg lysozyme (HEL),
      carcinoembryonic antigen (CEA), and HIV gpl20 (HIV). The diabodies were then
      evaluated in immunoassays. RESULTS: The HEL diabody was shown to recruit beta
      galactosidase in a microtiter plate immunoassay in which diabody and enzyme were
      co-incubated with antigen, washed and enzyme substrate added. The CEA diabody was
      shown to detect CEA by immunocytochemical staining of transfected, CEA-expressing
      HeLa cells and of adenocarcinoma colon tissue sections, and the HIV diabody to
      detect gpl20 in immunoblots of total cell extracts. CONCLUSION: The results
      illustrate the diagnostic potential of diabodies in enzyme immunoassays.

PMID- 9237099
TI  - pPV: a novel IRES-containing vector to facilitate plasmid immunization and
      antibody response characterization.
AB  - BACKGROUND: The ability to derive immunological reagents for basic and applied
      research in a timely fashion is a basic requirement of many research projects and
      is becoming increasingly important as the number of novel gene products of
      potential interest continues to evolve rapidly. DNA immunization provides a means
      of facilitating the production of antibody reagents by circumventing the need to
      derive either purified protein or define peptides before initiating an in vivo
      immunization protocol. OBJECTIVES: The DNA construct pPV, for plasmid
      vaccination, has been designed to facilitate the generation and characterization
      of antibody reagents against either random or defined molecular targets. STUDY
      DESIGN: pPV incorporates mammalian regulatory and structural features that
      promote expression of a bifunctional messenger RNA (mRNA) from a single promoter
      within mammalian cells both in vitro and in vivo. The bifunctional mRNA encodes a
      control epitope (human IL5), and the 'test' epitope expressed as a tagged
      recombinant polypeptide in either a random 'shot-gun' mode or a predetermined
      fashion. In addition, to aid subsequent characterization of antibody responses
      elicited in vivo, a T7 promoter is included to enable in vitro expression of
      tagged recombinant polypeptides. RESULTS: The utility and functionality of pPV
      for the in vitro expression of recombinant protein and the in vivo elicitation of
      antibody responses is illustrated using a defined 'test' epitope, human proIL1
      beta. CONCLUSION: It is anticipated pPV will find particular utility in the
      future rapid generation and characterization of antibody reagents against the
      plethora of novel genes emerging from ongoing genomics activity in a directed or
      genome wide fashion.

PMID- 9237100
TI  - Phage-displayed La/SS-B antigen as a diagnostic reagent.
AB  - BACKGROUND: The detection of antibodies to La/SS-B, a nuclear RNA-binding protein
      in mammalian cells, aids in the diagnosis of Sjogren's syndrome and systemic
      lupus erythematosus (SLE). This is performed conventionally by
      immunoprecipitation using a crude splenic extract and more recently, by the more
      sensitive and rapid enzyme-linked immunosorbent assay (ELISA) which uses a
      purified La/SS-B antigen. The latter antigen is obtained from cellular extracts
      of the antigen or from bacterial cell lysates containing the recombinant antigen
      usually by affinity chromatographic method. OBJECTIVE: To produce a La/SS-B
      antigen for use in ELISA that can be obtained easily and inexpensively without
      the need for extensive purification (including affinity chromatography). STUDY
      DESIGN: The antigen was produced as a fusion protein of the minor coat protein of
      M13 bacteriophage and used in this phage-associated form in an ELISA. La/SS-B
      cDNA derived from Hep-2 cells was cloned into the phagemid, pCANTAB-5E, and
      transfected to Escherichia coli. Phage clones selected for the presence of insert
      both by gene and antigenic analyses were used in the ELISA to detect anti-La/SS-B
      antibodies from patients with Sjogren's syndrome and SLE. RESULTS: A phage clone
      was obtained which contained a La/SS-B cDNA fragment truncated at the C-terminal
      end (after base-pair 631). The phage-displayed antigen derived from this clone
      was obtained by precipitation of the phage particles from the bacterial culture
      supernatant with polyethylene glycol. Used in the ELISA, this antigen detected 27
      of 28 precipitin-positive sera and was negative for 50 control sera. The soluble
      (phage-free) form of the antigen was obtained from a nonsuppressor host as a cell
      lysate which could not be used in this form in an ELISA for antibody detection.
      It was useable, however, in Western blot analysis which confirmed the reactivity
      of the recombinant antigen. CONCLUSION: Phage-displayed antigens may be used in
      place of soluble forms of these antigens in detection assays which have the
      advantage that they are easy and inexpensive to produce.

PMID- 9237101
TI  - Binding of copolymer 1 and myelin basic protein leads to clustering of class II
      MHC molecules on antigen-presenting cells.
AB  - Copolymer 1 (Cop 1), a synthetic copolymer of amino acids, effective in
      suppression of experimental allergic encephalomyelitis (EAE) and myelin basic
      protein (MBP), was shown to bind extensively and promiscuously to the class II
      MHC molecules on antigen-presenting cells (APC) without prior processing. In the
      case of human APC, binding has earlier been demonstrated to DR but not DQ or
      class I molecules. In the present study, we examined whether binding of Cop 1 and
      MBP affects MHC class II expression on the cell membrane. Biotinylated
      derivatives of these antigens were used to monitor their direct binding to MHC
      molecules on living APC by flow cytometry using phycoerythrin-streptavidin, while
      the levels of MHC surface expression were monitored by staining with FITC
      conjugated anti-class I- and class II-specific antibodies. When Cop 1 or MBP were
      incubated with the APC, intensity of cell staining with anti-DR, but not with
      anti-DQ or anti-class I antibodies, was significantly increased, compared to the
      staining of control APC not reacted with these antigens. In contrast, staining
      intensity was unaffected when p84-102, a human immunodominant epitope of MBP, or
      ovalbumin (OVA), a protein which undergoes proteolytic degradation prior to
      binding, were incubated with the APC. Cycloheximide, a protein synthesis
      inhibitor, had no effect on the enhanced staining intensity with anti-DR antibody
      of cells treated with Cop 1 or MBP, whereas it inhibited the enhanced staining of
      both DR and DQ molecules caused by the respective antibodies, in the absence of
      these antigens. Brefeldin A, a protein transport inhibitor, lowered the levels of
      staining intensity with anti-DR and anti-DQ antibodies in both cases, with and
      without antigen added to the APC. Fluorescence microscopic analysis revealed that
      cells incubated with Cop 1 or MBP, but not with p84-102 or OVA, exhibit both
      bright staining of the cell membrane and clusters produced by the aggregation of
      DR molecules with these antigens. Taken together, these observations indicate
      that Cop 1 and MBP, due to their polyvalent character, lead to increased
      fluorescence intensity of their complexes with HLA-DR, possibly due to
      recruitment and clustering of previously synthesized DR molecules. This can
      explain the efficient binding of these antigens to the MHC class II molecules.

PMID- 9237102
TI  - Immobilized anti-CD3 mAb induces anergy in murine naive and memory CD4+ T cells
      in vitro.
AB  - The induction of non-responsiveness in resting murine CD4+ T cells was
      investigated using immobilized anti-CD3 mAb. Incubation of freshly isolated CD4+
      T cells with immobilized anti-CD3 mAb led to apoptosis in 40-60% cells. The
      surviving cells were profoundly non-responsive to subsequent mitogenic
      stimulation. The non-responsive state was characterized by a lack of IL-2
      production and hyper-responsiveness to added IL-2, but was not explained by
      further activation-induced cell death. The induction of non-responsiveness was
      not due to modulation of the TCR-CD3 complex, and required partial activation of
      the T cells in that it was accompanied by an increase in cell size and was
      inhibited by addition of cyclosporin A. Finally, analysis of anti-CD3-mediated
      responses in naive and memory CD4+ T cells, separated on the basis of CD44
      expression, showed that both naive and memory T cells have similar sensitivity to
      immobilized anti-CD3 mAb-induced activation, apoptosis and anergy. These results
      demonstrate that TCR-CD3 engagement on freshly isolated resting CD4+ naive and
      memory T cells, In the absence of co-stimulation, as achieved by plastic
      immobilized anti-CD3 mAb, induces both anergy and cell death.

PMID- 9237103
TI  - Elevated expression of Bcl-2 and Bcl-x by intestinal intraepithelial lymphocytes:
      resistance to apoptosis by glucocorticoids and irradiation.
AB  - Administration of glucocorticoids or exposure to ionizing radiation in vivo
      results in a rapid cell death of thymocytes. We report that murine small
      intestinal intraepithelial lymphocytes (IEL) are resistant to both steroid- and
      radiation-induced deletion. This is due to resistance to apoptosis, as evidenced
      by the absence of detectable apoptotic IEL nuclei in situ after in vivo
      glucocorticoid treatment. IEL express normal levels of glucocorticoid receptors
      and these receptors bind [3H]dexamethasone to equivalent levels as other
      lymphocyte populations. Thus, their survival is due to post-receptor signaling
      mechanisms. Many IEL express high levels of Bcl-2 and that of these Bcl-2high IEL
      are largely TCR gamma delta +. Those IEL that do express high levels of Bcl-2 are
      CD8 alpha + beta - CD4-. In addition, IEL express Bcl-x, another protein shown to
      be involved in the protection of cells from apoptotic signals. IEL represent the
      first lymphocyte population in vivo shown to have high levels of expression of
      both molecules, that otherwise occur only in activated lymphocytes in vitro.
      These data suggest that the Bcl-2+Bcl-x+ IEL are activated cells and not an
      effete population of cells necessarily destined to die. Also, the high levels of
      Bcl-2 and Bcl-x in this in vivo activated population supports the in vitro
      correlate of protection from activation-induced cell death.

PMID- 9237104
TI  - Selective usage of defined TCRBV genes in response to filarial antigens.
AB  - The characterization of T cell reactivities that are prone to down-modulation by
      filarial parasites is central to understanding how these nematodes can survive
      for long periods of time within their human host and to design appropriate
      immunoprophylactic measures. In the present study, TCRBV gene usage was analyzed
      in response to filarial antigens by PCR using a panel of TCRBV gene segment
      family-specific oligonucleotide primers. Analysis of individuals highly
      responsive to Brugia malayi adult worm antigen (BmA) (n = 4) indicated that
      following stimulation with BmA a maximum of four TCRBV gene families were over
      represented in each subject. Those were TCRBV2, 9, 19 and 23 in subject 1;
      TCRBV8, 9 and 16 in subject 2; TCRBV2, 8, 9 and 11 in subject 3; and TCRBV13 and
      23 in subject 4. The analysis of one subject who was unresponsive to BmA before
      but regained responsiveness after diethylcarbamazine treatment revealed that
      there was no overexpression of a particular TCRBV gene family before
      chemotherapy, whereas after chemotherapy three TCRBV gene families (TCRBV8, 16
      and 19) were found to be overexpressed. Complementarity determining region 3 size
      analysis of a selection of the overexpressed TCRBV genes displayed oligoclonality
      in some of the observed expansions. Together these observations show that limited
      T cell subpopulations are clonally amplified in BmA-stimulated peripheral blood
      mononuclear cells of filarial responder subjects, possibly driven by a restricted
      number of antigens.

PMID- 9237105
TI  - Antibody class switch recombinase activity is B cell stage specific and functions
      stochastically in the absence of 'targeted accessibility' control.
AB  - Chromosomally integrated retroviral switch (S) substrates have been developed to
      reveal switch recombinase-like activities (SRLA) in pre-B and mature B cell
      lines. Switch substrate retrovectors (SSR) contain a long-terminal repeat-driven
      neomycin (Neo) gene for proviral chromosomal maintenance (pre- and post-S
      recombination) and a CMV promoter-driven, chimeric hygromycin-thymidine kinase
      (Hytk) gene (flanked by S mu and S gamma 2b recombination targets) to select for
      (ganciclovir) and against (hygromycin B) S region recombination. The retro
      substrates' strong, constitutive promoters ensure that variations in cellular
      switch recombinase activities are independent of S region accessibility control.
      By initially selecting for proviral integrants in hygromycin followed by shifting
      into neomycin + ganciclovir to select for S sequence-mediated deletions, switch
      recombinations can be specifically forestalled in B cell lines whilst most switch
      incompetent cells do not survive secondary selection. A qualitative, direct PCR
      assay reveals that SSR recombinations are stochastic in B cell lines generating a
      product array akin to natural GH class switching. A semi-quantitative DC-PCR
      assay detects a significant recombinase activity only in a restricted set of late
      stage pre-B and mature B cell lines. BCL1B1 mature B cells have the highest level
      of recombinase activity with 25% or more of proviral integrants accumulating S
      mu/S gamma 2b substrate recombinations within 10-14 cell generations. The SSR
      recombinase assay can be performed in a transient fashion wherein extensive, B
      cell-specific recombination can be visualized within only a few cell divisions
      post proviral integration. We propose that switch recombinase activity becomes
      activated during B cell ontogeny independent of or prior to the acquisition of CH
      locus accessibility and that endogenous S segment targeting to pre-existing
      recombinase requires a level of accessibility beyond transcriptional activation.

PMID- 9237106
TI  - Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents
      cyclosporin A and rapamycin.
AB  - T cell cytokine expression may be induced by the cytokine IL-2 or via the TCR
      complex. The comparative effects of cytokine- and TCR-mediated signalling on the
      induction of human IL-5 mRNA were examined. Cytokine mRNA expression was analysed
      by RT-PCR in fresh peripheral blood mononuclear cells (PBMC) from normal
      individuals and in populations of activated T lymphocytes, derived from
      phytohaemagglutinin (PHA)-stimulated PBMC. rIL-2 induced IL-5 expression in PBMC,
      the kinetics of which were similar to the effects of PHA. rIL-4 induced IL-5 mRNA
      expression in activated T lymphocytes. IL-5 expression induced by either IL-2 or
      PHA was completely abolished by the protein synthesis inhibitor cycloheximide.
      rIL-2-induced IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5
      expression elicited by PHA was inhibited by CsA, at doses as low as 10 ng/ml.
      Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression, but suppressed
      IL-5 expression induced by PHA. The inhibitory effect of RAP on PHA-induced IL-5
      expression was more apparent at 12 and 24 h after stimulation than at earlier
      times. The resistance of IL-2 receptor (IL-2R) signalling to CsA and RAP
      indicates that the IL-2R and the TCR are associated with different pathways
      regulating IL-5 expression.

PMID- 9237107
TI  - Both invariant chain isoforms Ii31 and Ii41 promote class II antigen
      presentation.
AB  - The invariant chain (Ii) gene encodes two differentially spliced variants Ii31
      and Ii41. The Ii31 isotype is the dominant form expressed in all antigen
      presenting cells (APC). Ii41 is differentially expressed and can be found in
      large quantities in Langerhans and dendritic cells. While a functional role of Ii
      in class II antigen presentation is now well established, a distinct role of the
      Ii isotypes remains controversial. We tested Ii31 and Ii41 L cell transfectants
      for antigen presentation of hen egg lysozyme (HEL) to T cell hybridomas. The
      result indicates that both Ii chains promote antigen presentation equally well.
      To test other APC than transfected L cells, we introduced a recombinant Ii41 gene
      into anti-deficient mouse line. There the transgene induces about one-third of
      total li expression of wild-type mice. Surface expression of class II molecules
      and the CD4 compartment which are deficient in Ii knock-out mice are restored in
      Ii41 transgenic mice. B lymphocytes from Ii41 transgenic mice and Ii31-expressing
      B lymphocytes from wild-type mice were used as APC for presentation of keyhole
      limpet hemacyanin and ovalbumin to T cell hybridomas. The results show that both
      Ii chains facilitate antigen presentation equally well.

PMID- 9237108
TI  - Characterization of rat CD80 and CD86 by molecular cloning and mAb.
AB  - The CD28/B7 pathway provides a critical co-stimulatory signal for T cell
      activation. In the present study, we cloned rat CD80 and CD86 cDNA from a HTLV-1
      transformed rat T cell line, Lewis-S1, expressing a high level of CTLA-4-Ig
      binding proteins. The predicted CD80 and CD86 polypeptides were composed of 321
      and 313 amino acids respectively, and exhibited features common to human and
      mouse B7 family proteins. Both CD80 and CD86 mRNAs were abundantly detected in
      HTLV-1-transformed rat T cell lines but not in a thymic lymphoma cell line. To
      further explore the function of rat CD80 and CD86, we generated cDNA
      transfectants and anti-rat CD80 (3H5) and anti-rat CD86 (24F) mAb. Rat CD80 or
      CD86 transfectants exhibited a potent co-stimulatory activity for rat T cell
      proliferation, which was blocked by 3H5 and 24F mAb respectively. 3H5 or 24F
      immunoprecipitated a 80-90 or 90-100 kDa surface protein from Lewis-S1 cells.
      HTLV-1-transformed rat T cell lines expressed high levels of both CD80 and CD86
      as estimated by staining with 3H5 and 24F, which acted co-stimulatory for
      allogeneic T cell activation as estimated by blocking with 3H5 and 24F. These mAb
      will be useful for investigating the pathophysiological functions of CD80 and
      CD86 in transplantation, autoimmune diseases and HTLV-1-associated pathologies in
      the rat system.

PMID- 9237109
TI  - Modulation of CD72 by ligation of B cell receptor complex molecules on CD5+ B
      cells.
AB  - B cells expressing CD5 also carry its ligand, CD72. As an approach to
      understanding the role of CD5 and CD72 on B cells, we have examined the
      association of CD72 with CD5 and slgM by modulation/co-modulation and capping/co
      capping following ligation of these surface molecules with specific antibodies.
      Modulation and co-modulation were measured after 24 h, whilst capping was
      measured after 1 h. CD5 and slgM co-modulated each other, CD72 co-modulated with
      slgM and CD5, but anti-CD72 did not affect either slgM or CD5. CD5 and slgM co
      capped each other, whilst CD72 failed to co-cap with either slgM or CD5. The CD5
      induced co-modulation of CD72 was partially blocked by specific protein tyrosine
      kinase inhibitor, but not the slgM-induced co-modulation, Protein kinase C (PKC)
      inhibitors abrogated the anti-mu- but not the anti-CD5-triggered modulation of
      CD72, whereas PKC activators prevented the CD5- but not the slgM-induced 24 h
      modulation of CD72. None of these drugs was able to modify the anti-CD72-induced
      modulation of CD72. Our data suggest that CD5 is physically associated with slgM
      in the B cell receptor complex but not with CD72. Furthermore, from the effect of
      drugs on modulation, there appears to be different associations of CD72 with slgM
      and CD5. These two pathways differed in some respects, consistent with a co
      stimulatory function of CD72 and CD5 in B cell activation.

PMID- 9237111
TI  - Ig S gamma-specific DNA binding protein SNAP is related to the helix-loop-helix
      transcription factor E47.
AB  - SNAP, a DNA-binding protein, is specific for the S gamma switch regions. Two E-2
      box consensus binding motifs are located within the SNAP recognition site. Direct
      and competition-binding analyses demonstrate that a truncated form of the E47
      transcription factor, E47S, is capable of specific interactions with the SNAP
      binding motif. The methylation interference pattern for E47S binding on the pl.S
      gamma 3.A.1 probe was similar to that previously obtained for SNAP binding
      activity and was also related to that found for E47S on the microE5 probe. The
      interaction of purified E47S with the SNAP recognition motif was cooperative and
      formed complexes which migrated more slowly than the E47S homodimer complex. SNAP
      is distinguished from full-length E47 homodimers, found in BCF-1, by its
      migration position in the gel shift assay, differences in the competition-binding
      results and its unique reactivity with anti-E47 antibodies. SNAP is related to
      E47 as judged by a similar methylation interference pattern on S gamma 3 A site
      DNA and by its reactivity with anti-E47 mAb. The anti-E47 antibodies block SNAP
      binding to its cognate site, whereas anti-E47 antibodies supershift E47
      homodimers bound to the microE5 recognition site. Thus, SNAP may be a hetero
      oligomeric species containing E47 or highly related proteins.

PMID- 9237110
TI  - Direct evidence for the commitment of hematopoietic stem cells to T, B and
      myeloid lineages in murine fetal liver.
AB  - We established an experimental system in vitro to examine the developmental
      capacity of individual hematopoietic progenitors to generate T, B and myeloid (M)
      cells. By using this system we analyzed the process of lineage commitment of
      hematopoietic progenitors in murine fetal liver (FL). It is known that small
      numbers of B and M cells, in addition to T cells, are generated in a co-culture
      of hematopoietic progenitors and a deoxyguanosine-treated fetal thymus (FT) lobe.
      We tried to enhance the growth of B and M cells by the addition of IL-7, IL-3 and
      stem cell factor into the co-culture. This cytokine-supplemented FT organ culture
      was used to examine the developmental capacity of individual hematopoietic
      progenitors in FL. Single cells of lineage marker (Lin)-c-kit+Sca-1+ (Sca-1+) and
      Lin-c-kit+Sca-1-(Sca-1-) populations from the FL harvested at day 12 of gestation
      were cultured for 10 days, and the phenotypes of cells generated in each lobe
      were analyzed with a flow cytometer. All progenitors in the Sca-1- population
      were shown to be committed to generate only T, B or M cells. On the other hand,
      multipotent progenitors, which are capable of generating T, B and M cells, as
      well as unipotent progenitors committed to the T, B or M lineage were found in
      the Sca-1+ population. Bipotent progenitors generating M and T cells and those
      generating M and B cells were also found in the Sca-1+ population, which probably
      represent progenitors in the process of commitment. However, no bipotent
      progenitors generating T and B cells were detected.

PMID- 9237112
TI  - Clonal expansion and decreased occurrence of peripheral blood gamma delta T cells
      of the V delta 2J delta 3 lineage in multiple sclerosis patients.
AB  - gamma delta T cells are implicated in autoimmune diseases but their precise
      function remains unclear. In multiple sclerosis (MS) brain tissue, gamma delta T
      cells co-localize with heat shock protein (hsp)65+ oligodendrocytes and are
      oligoclonally restricted in the V delta 2J delta 3 lineage. To investigate the
      homing properties and the degree of heterogeneity of V delta 2J delta 3+ gamma
      delta T cells in MS, peripheral blood lymphocytes (PBL) from 34 MS patients, 42
      controls (14 autoimmune control patients, 28 healthy volunteers), and 11
      lymphatic tissues of MS patients and controls were studied by RT-PCR and
      sequencing. V delta 2J delta 3 TCR rearrangement was detected in 27 out of 28
      healthy controls, and was significantly less frequent in MS patients (24 out of
      34) and autoimmune control patients (seven out of 14). It was present only in
      five out of 11 tissue specimens, none of them from MS patients. Direct sequencing
      and cloning/automated sequencing of the V delta 2J delta 3 PCR products indicated
      heterogeneity in healthy controls and oligoclonality in MS patients, but also in
      autoimmune control patients. Differences between MS patients and healthy controls
      were more accentuated in exacerbating hospitalized patients than in clinically
      stable outpatients participating in a clinical trial. Only one V delta 2J delta 3
      sequence of a total of 85 different sequences obtained was shared between two MS
      patients. Taken together, evidence for clonal expansion of V delta 2J delta 3+
      gamma delta T cells was found in PBL of MS patients. This T cell subset,
      previously shown to be present in 100% of chronic-active MS plaques, might home
      to the CNS in MS, resulting in its under-representation in the blood.

PMID- 9237113
TI  - Cloning, functional activities and in vivo tissue distribution of rat NKR-P1+ TCR
      alpha beta + cells.
AB  - We have successfully cloned nine NKR-P1+ TCR alpha beta + cells from PVG rat
      spleens, utilizing murine macrophage inflammatory protein-1 alpha (MIP-1 alpha)
      and IL-2. These clones are either double negative (DN, CD4-CD8-), which included
      clones 3.31, 3.71, 4.19, 4.59 and 4.65, or single positive (SP, CD4+CD8-), which
      included clones 1.64, 3.8, 3.76 and 3.78. No CD8+ clone was recovered. All nine
      clones are restricted in terms of their expression of the V beta antigens, since
      they express V beta 8.2 but not V beta 8.5, V beta 10 or V beta 16. These clones
      are agranular and they fall to generate NK or LAK activity upon incubation with
      IL-2, IL-12 or their combination. On the basis of their production of
      intracellular cytokines they can be divided into three categories: (I) SP clones
      (1.64, 3.8, 3.76 and 3.78) do not produce IL-2 or IL-4, but produce IFN-gamma and
      IL-12, and they vary in their production of IL-1, RANTES or tumor necrosis factor
      (TNF)-alpha; (II) DN clones 4.59 and 4.65 produce IL-1 alpha and IFN-gamma only,
      and fall to produce other cytokines; and (III) DN clones 3.31, 3.71 and 4.19
      produce IL-1 alpha, IL-1 beta, IL-2, IL-12, IFN-gamma, RANTES and TNF-alpha. From
      all the clones examined only DN clones 3.31 and to a lesser degree 4.19 produce
      IL-4. In vivo tissue localization of clones 3.8, 3.31 and 4.59 shows that these
      cells distribute into the liver and bone marrow 24 h post i.v. administration.
      Their accumulation in the liver and bone marrow along with their ability to
      secrete various cytokines suggest that these cells may influence the generation,
      differentiation or apoptosis of immune or hematopoietic cells.

PMID- 9237114
TI  - Breakdown of T cell tolerance to IgG2ab in Igha mice by de novo emerging anti
      IgG2ab T cells and not anergy reversion.
AB  - The intrinsic T cell activity of Igha mice against IgG2ab (IgG2a from the Ighb
      haplotype) can be subjected to profound specific tolerance. In utero followed by
      post-natal exposure of Igha mice to soluble IgG2ab results in the loss of the
      capacity of their T splenocytes to induce specific and chronic IgG2ab allotype
      suppression in histocompatible Igha/b recipients. However, this full T cell
      tolerance has not been definitively acquired as it is spontaneously reversed when
      investigated 3-6 months after the end of the tolerogen treatment. Even when the
      IgG2ab tolerogen treatment was prolonged to 3, 6 or 9 months of age, T cell
      tolerance to IgG2ab vanished and the capacity of Igha T splenocytes to induce
      IgG2ab suppression in Igha/b recipients was systematically restored. The marked
      but partial thymus involution in 15-month-old Igha mice suggests the existence of
      some residual thymic output, capable of repopulating the anti-IgG2ab peripheral T
      pool subsequent to tolerogen clearance. In the present study, we showed that the
      mechanisms of this tolerance and its reversion involve, at the end of tolerogen
      treatment, the physical elimination or the irreversible inactivation of natural
      anti-IgG2ab T cell clones and their replacement, but neither the establishment of
      reversible anergy nor the recruitment of T cells which could actively maintain
      tolerance. The spontaneous breakdown of this T cell unresponsiveness was
      effectively prevented when de novo T cell maturation was inhibited by thymectomy
      at the end of tolerogen administration. Moreover, tolerance reversion did not
      occur in peripheral mature Igha T cells, parked in vivo, for up to 20 weeks in
      histocompatible tolerogen-free nu/nu mice.

PMID- 9237115
TI  - Are CD8+ dendritic cells (DC) veto cells? The role of CD8 on DC in DC development
      and in the regulation of CD4 and CD8 T cell responses.
AB  - The CD8-expressing dendritic cells (DC) present in mouse spleen have been shown
      to have a regulatory effect on the CD4 and CD8 T cells they activate, restricting
      subsequent T cell proliferation by either inducing apoptotic T cell death (CD4 T
      cells) or by limiting endogenous cytokine production (CD8 T cells). To determine
      the role of the CD8 molecule itself in these regulatory phenomena, the DC from
      CD8 null mice were studied. The DC marker DEC-205 (NLDC 145) was used as a
      surrogate marker for CD8, since the expression of these two molecules on splenic
      DC was closely correlated. DC levels were normal, and the incidence of DEC-205+
      and DEC-205- DC was normal in CD8 null mice, indicating that the absence of CD8
      did not affect DC development. The proliferative response of T cells to
      allogeneic DEC-205+ DC from either CD8-/- or CD8+/+ mice was similar and was much
      less than the response to DEC-205- DC from these mice. This applied to both the
      CD4 and the CD8 T cell responses. Thus the lack of the CD8 molecule did not
      affect the stimulatory or regulatory properties of the DC. The regulatory CD8+
      DEC-205+ DC therefore differ in that respect from antigen-presenting 'veto'
      cells, where CD8 itself is involved in transmitting negative signals to the T
      cells. DEC-205 may prove to be a more pertinent marker of the regulatory DC
      population.

PMID- 9237116
TI  - Rapid purification, partial characterization, and antimicrobial spectrum of the
      bacteriocin, Pediocin AcM, from Pediococcus acidilactici M.
AB  - The bacteriocin from Pediococcus acidilactici M, designated as Pediocin AcM, was
      rapidly purified to homogeneity by the pH mediated cell adsorption-desorption
      method and semi-preparative reversed-phase HPLC. The purification yield was 40.4%
      and the specific activity was increased by 2450-fold. It gave a single band and a
      single peak on SDS-PAGE and HPLC analysis, respectively. When subjected to
      electrospray LC-MS analysis, the protein was found to be highly pure and the
      molecular weight was determined as 4,618 Da. High concentration of the
      bacteriocin (> 50 micrograms/ml) showed good resistance to extremes of pH (1-12)
      and temperature (121 degrees C). Pediocin AcM was deduced to be a monomer with an
      intra-peptide disulfide bond from the results of reversed-phase analytical HPLC
      analyses after reduction, oxidation and trypsin digestion. P. acidilactici M
      inhibited a large number of bacteria, including Staphylococcus aureus, Listeria
      monocytogenes, Clostridium perfringens, Bacillus coagulans, B. cereus, and
      Aeromonas hydrophila.

PMID- 9237117
TI  - Evaluation of the NASBA nucleic acid amplification system for assessment of the
      viability of Campylobacter jejuni.
AB  - Although NASBA uses RNA as a target molecule for amplification, the nucleic acid
      amplification system cannot be used for differentiating viable and non-viable C.
      jejuni. It was shown that 16S rRNA, or the defined sequence within the 16S rRNA
      enclosed by the primer set applied, is fairly stable and resistant to heating at
      100 degrees C. False-positive results can occur in case of direct NASBA detection
      of C. jejuni in foods. These false positive results due to amplification of RNA
      from dead cells were eliminated by prior selective enrichment in Preston medium
      for 24 h at 42 degrees C.

PMID- 9237118
TI  - The effects of bakery processing on natural deoxynivalenol contamination.
AB  - The aim of this study was the evaluation of the influence of the breadmaking
      process on initial deoxynivalenol (DON) contamination. Samples (92) were taken
      from four batches of eight different types of products in a low-technology
      bakery. The final products, as well as the corresponding flours, doughs and
      fermented doughs were analyzed. Extracts were obtained with acetonitrile:water
      (84:16), the clean up was made with a multifunctional column and DON was
      quantified by thin layer chromatography by visual comparison with standards.
      Confirmation was made by electron capture gas chromatography. The contamination
      levels in flour samples ranged from 500 micrograms/kg to 2000 micrograms/kg on
      dry weight basis. The results showed a positive correlation between the initial
      contamination level and the reduction of DON after fermentation. A significant
      reduction was observed as a consequence of the breadmaking process.

PMID- 9237119
TI  - Seminested RT-PCR systems for small round structured viruses and detection of
      enteric viruses in seafood.
AB  - Highly sensitive seminested RT-PCR systems for the specific detection of genotype
      I and II small round structured viruses (SRSVs) were developed based on the
      nucleic acid information deposited in the databanks. SRSVs could be detected in
      10(7)-fold dilutions of three different stool samples. In addition, a rapid and
      simple purification protocol for enteric viruses from seafood tissues was
      elaborated using poliovirus (PV) as model. The virus isolation and viral RNA
      purification include the following steps: elution of the viruses from the seafood
      tissue with glycine buffer, their concentration by PEG-precipitation, lysis of
      viral particles with guanidine hydrochloride and viral RNA isolation using a
      silica based membrane. The detection limit was 3 to 30 TCID50 of poliovirus in
      1.25 g of seeded seafood tissues without marked food matrix differences, whereas
      SRSV viruses were 10- and 100-fold better detected in mussels than in shrimps and
      oysters, respectively. The newly developed purification method, which was shown
      to remove potential RT-PCR inhibitors present in mussel tissue samples, was
      applied in a small market survey. 15 mussels, 15 oysters and 12 shrimps were
      examined for the presence of Hepatitis A virus (HAV), Enterovirus (EV), Rotavirus
      (RV) and SRSV using specific RT-PCR detection systems. The finding of three
      oyster samples positive for Rotavirus demonstrated the successful application of
      our method for the detection of enteric viruses in naturally contaminated seafood
      samples. The rapid isolation method might be suitable for application in routine
      testing laboratories and will help to improve public health controls for seafood.

PMID- 9237120
TI  - Predictive model of the effect of CO2, pH, temperature and NaCl on the growth of
      Listeria monocytogenes.
AB  - The growth responses of L. monocytogenes as affected by CO2 concentration (0-100%
      v/v, balance nitrogen), NaCl concentration (0.5-8.0% w/v), pH (4.5-7.0) and
      temperature (4-20 degrees C) were studied in laboratory medium. Growth curves
      were fitted using the model of Baranyi and Roberts, and specific growth rates
      derived from the curve fit were modelled. Predictions for specific growth rate,
      doubling time and time to a 1000-fold increase could be made for any combination
      of conditions within the matrix. Predictions of growth from the model were
      compared with published data and this showed the model to be suitable for
      predicting growth of L. monocytogenes in a range of foods packaged under a
      modified atmosphere.

PMID- 9237121
TI  - Viability of Escherichia coli O157:H7 in pepperoni during the manufacture of
      sticks and the subsequent storage of slices at 21, 4 and -20 degrees C under air,
      vacuum and CO2.
AB  - A raw, pepperoni batter (75% pork:25% beef with a fat content of about 32%) was
      inoculated with a pediococcal starter culture (about 10(8) cfu/g) and a five
      strain cocktail of Escherichia coli O157:H7 (> or = 2 x 10(7) cfu/g), mixed with
      non-meat ingredients, and then hand-stuffed into 55 mm fibrous casings to form
      sticks. The numbers of the pathogen were determined before stuffing, after
      fermentation, after drying/slicing, and after periods of storage. For storage,
      slices were packaged under air, vacuum or CO2 and stored at -20, 4 and 21 degrees
      C. Sticks were fermented at 36 degrees C and 85% relative humidity (RH) to < or =
      pH 4.8 and then dried at 13 degrees C and 65% RH to a moisture/protein ratio
      (M/Pr) of < or = 1.6:1. Fermentation and drying resulted in the numbers of the
      pathogen decreasing by about 2 log10 units. During storage, the temperature
      rather than the atmosphere had the greater effect on pathogen numbers. The
      greatest reductions in numbers were observed during storage at 21 degrees C, when
      numbers decreased to about 2 and 3.8 log10 cfu/g within 14 days in product stored
      under air and vacuum, respectively, and a 5 log10 reduction was observed for both
      atmospheres within 28 days. Regardless of the storage atmosphere, numbers did not
      decrease below 3.6 or 3.7 log10 cfu/g after 90 days of storage at -20 or 4
      degrees C, respectively. These data confirm that fermentation and drying are
      sufficient to eliminate only about 2 log10 cfu/g of E. coli O157:H7 from
      fermented sausage, and that additional strategies, such as storage for at least 2
      weeks at ambient temperature in air, are required to achieve a 5 to 6 log10
      reduction in the numbers of the pathogen in sliced pepperoni.

PMID- 9237122
TI  - Detection of Salmonella from raw food samples using Dynabeads anti-Salmonella and
      a conventional reference method.
AB  - A Dynal core method has been established using Dynabeads anti-Salmonella to
      detect Salmonella from all categories of food samples. The protocol consists of
      the standard pre-enrichment of samples in buffered peptone water followed by
      immunomagnetic separation and subsequent selective enrichment of the bead
      bacteria complexes in Rappaport-Vassiliadis Soya Peptone broth before plating
      onto Salmonella selective media. This modified IMS cultural method is intended to
      replace or augment traditional cultural methods used for Salmonella detection due
      to its specificity and increased sensitivity. The optional direct plating of bead
      bacteria complexes onto solid media using a swab-streak technique is suitable for
      processed foods or samples known to have a history of very low resident flora. In
      an evaluation using 100 naturally contaminated samples, this IMS core method
      detected 39 of the 44 positive samples detected by all the methods combined,
      compared to 31 detected by the conventional ISO 6579 reference method.
      Furthermore, in ten different food matrices inoculated with low levels (1-5
      cells/25 g) of twenty Salmonella serovariants, frozen for one month before being
      examined, the IMS core method, showed a 90% concordance with the ISO method and
      isolated two more Salmonella positive samples than the conventional ISO method.

PMID- 9237123
TI  - Sodium nitrite and potassium nitrate in control of nonproteolytic Clostridium
      botulinum outgrowth and toxigenesis in vacuum-packed cold-smoked rainbow trout.
AB  - The effect of sodium-nitrite (NaNO2) and potassium nitrate (KNO3) on the
      outgrowth and toxigenesis of nonproteolytic Clostridium botulinum in vacuum
      packed cold-smoked rainbow trout stored for-six weeks was studied in two
      inoculation studies at slightly abusive storage temperatures of 4 degrees C and 8
      degrees C. The depletion rate of nitrite and the reduction rate of nitrate to
      nitrite as well as the effect of nitrite and nitrate on the shelf-life of the
      product during eight weeks' storage period were also determined. The nitrite
      concentrations were reduced from 166 mg/kg +/- 9 (mean +/- SE), to a final
      concentration of 34 mg/kg +/- 2 and 11 mg/kg +/- 2, and the nitrate
      concentrations from 686 mg/kg +/- 67 to 465 mg/kg +/- 140 and 427 mg/kg +/- 33 at
      4 degrees C and 8 degrees C respectively. The nitrite depletion rate was more
      rapid at 8 degrees C; nitrate depletion was not significantly affected by
      temperature. A considerable amount of nitrite was detected in the nitrate-treated
      samples in the latter half of the storage period. At 4 degrees C the aerobic
      plate counts were significantly lower in the samples treated with NaNO2 + NaCl
      and with KNO3 + NaCl as compared to the NaCl-treated controls, while at 8 degrees
      C the differences were smaller. The sensorial shelf-life of the product was
      considerably extended by nitrite and nitrate curing. The nitrite and nitrate
      concentrations used in the present study did not completely inhibit the
      toxigenesis of nonproteolytic C. botulinum during the six-week storage period,
      although the number of toxic samples was considerably reduced by nitrite and
      nitrate curing.

PMID- 9237124
TI  - Preparation of PCR samples from food by a rapid and simple centrifugation
      technique evaluated by detection of Escherichia coli O157:H7.
AB  - A sample treatment method based on buoyant density centrifugation which separates
      bacteria from food, concentrates bacteria and removes PCR inhibitors is
      described. The method involves a one minute centrifugation of food homogenate
      layered over a gradient medium (Percoll or BacXtractorTM) in Eppendorf tubes,
      followed by a single wash step. The small scale of this treatment makes it
      possible to process many samples in a short time. To evaluate the method beef and
      minced beef samples, spiked with strains of Escherichia coli O157:H7, were
      treated and then analysed by PCR aimed at verocytotoxin- (VT1 and VT2) and eae
      genes. The detection limits in 1:10 (w/v) beef and minced beef homogenates were
      125-250 cfu ml-1 (1250-2500 cfu g-1) and 1000 cfu ml-1 (1 x 10(4) cfu g-1),
      respectively. The enrichment of spiked samples in buffered peptone water at 37
      degrees C for 6 hours before buoyant density centrifugation and PCR, allowed 0.5
      cfu g-1 beef and 5 cfu g-1 minced beef to be detected. This combination of
      enrichment and buoyant density centrifugation was also used for analysis of 43
      beef samples from a consignment in which E. coli O157:H7 had been detected, and
      detected VT-genes in all 43 samples. E. coli O157:H7 was also separated and
      detected in spiked samples of milk, lettuce, shrimps, and blue cheese at
      arbitrary concentrations of 3000 cfu ml-1. The present sample preparation method
      has the potential to be applicable to many other combinations of bacteria and
      food, and in connection with other detection methods than PCR as well.

PMID- 9237125
TI  - Lactobacillus rhamnosus GG (ATCC 53103) and platelet aggregation in vitro.
AB  - Lactobacillus rhamnosus GG is an experimentally and clinically well documented
      probiotic used in different dairy products. The present study aimed to
      investigate the safety aspects of Lactobacillus rhamnosus GG, particularly with
      respect to platelet aggregation, the initiating event in thrombosis. Platelet
      rich plasma was separated from the blood of healthy volunteers, and the effects
      of Lactobacillus rhamnosus GG (ATCC 53103), Lactobacillus rhamnosus (ATCC 7469)
      and Enterococcus faecium T2L6 in different dilutions on spontaneous, ADP- and
      adrenaline-induced aggregation were tested. The bacteria did not influence
      spontaneous aggregation. Only Enterococcus faecium T2L6 enhanced the adrenaline
      induced aggregation, with a less clear effect on ADP-induced aggregation.

PMID- 9237126
TI  - Characterization of monoclonal antibodies for the rapid detection of foodborne
      campylobacters.
AB  - The specificity of 97 monoclonal antibodies (MAbs) to the Campylobacter jejuni
      Lior serogroup 6 reference strain was assessed using an indirect enzyme linked
      immunosorbent assay (ELISA). Four MAbs, M316, M337, M357 and M637, reacted with
      whole cells of the C. jejuni, C. coli and C. lari reference strains of the 20
      most common Lior serogroups and 25 recent C. jejuni and C. coli isolates, and did
      not react with most of the 42 other Campylobacter and non-Campylobacter spp.
      tested. Immunoblot analysis revealed that MAbs M337 and M357 reacted with a
      protein component with molecular mass of approximately 62 kiloDaltons (kDa) while
      M316 and M637 reacted with protein components of approximately 92 and 31 kDa,
      respectively. The detection limit of M357 in an indirect ELISA was 10(5) colony
      forming units. These four highly specific MAbs may be useful reagents of an
      immunoassay for the rapid detection of thermophilic campylobacters in foods and
      clinical samples.

PMID- 9237127
TI  - Alcohol liberates dye of syringes.
AB  - Foreign particles may contaminate intraocular surgery and have a role in
      postoperative inflammation. Irrigation solutions, viscoelastics, air and
      instruments introduced into the eye may carry in a number of organic or
      inorganic, inert or reactive foreign material. Dye of colored indicators on
      syringes may also behave as an unrecognized contaminant. This dye material is
      easily released from syringes by exposure to alcohol. The significance of dye
      contamination and possible outcomes were discussed.

PMID- 9237128
TI  - Retained perfluorodecalin after retinal detachment surgery.
AB  - Liquid perfluorocarbons such as perfluorodecalin are widely used as
      intraoperative vitreous substitutes in certain complicated vitreoretinal
      conditions. Retained perfluorodecalin postoperatively has been reported to be
      associated with retinal damage and other complications. We report on a case of
      retained intraocular perfluorodecalin for eleven postoperative days after retinal
      detachment surgery with good anatomical and visual outcome after one year follow
      up.

PMID- 9237129
TI  - Long-term evaluation of primary anterior chamber intraocular lens implantation in
      complicated cataract surgery.
AB  - The long-term visual outcome and complications related to the use of a
      semiflexible open-loop all-PMMA anterior chamber intraocular lens were evaluated
      in 40 eyes in which the capsular support was lost. The mean follow up time was
      2.3 years (range 6 months to 6.7 years). 55% of the eyes had exfoliation
      syndrome. 68% (27 of 40 eyes) obtained a visual acuity of 0.5 or better, and only
      in one of the remaining eyes decreased visual acuity was related to cataract
      surgery (cystoid macular oedema). No cases of corneal decompensation, uveitis
      glaucoma-hyphaema syndrome or retinal detachment have developed, and no IOLs have
      been explanted. Based on these results, the use of a modern anterior chamber
      intraocular lens can be suggested at least in old persons, if the capsular
      support is lost.

PMID- 9237130
TI  - Retinal detachment after cataract surgery.
AB  - BACKGROUND: A study of the characteristics and the results obtained in 99
      consecutive eyes operated on for rhegmatogenous retinal detachment associated
      with aphakia or pseudophakia in order to find the predictive factors of poor
      anatomical and functional results. METHODS: The authors retrospectively reviewed
      the files of 99 consecutive cases of aphakic and pseudophakic retinal detachment
      operated on by the same surgeon between January 1992 through July 1993 with a
      minimum follow-up of 6 months. Multivariate and chi square analysis were carried
      out. RESULTS: Of the pseudophakic eyes, 25 had an anterior chamber lens and 48
      had a posterior chamber lens. The posterior capsule was disrupted using a Yag
      laser in 58% of those with an posterior chamber lens but only 14% of them
      developed detachment within 6 months. The rate of vitreous loss was 27% with 5%
      in case of intracapsular extraction, 31% in case of extracapsular extraction and
      54% in case of phacoemulsification. PVR was present in 30% of the patients and
      51% of detachments occurred more than 24 months as a mean after cataract surgery.
      The overall anatomic reattachment rate was 88% with no significant difference
      between the aphakic and the pseudophakic patients, either with an anterior
      chamber of posterior chamber lens. Visual results were significantly worse in the
      anterior chamber lens group and in the aphakic eyes (P < 0.02). Negative
      prognostic indicators for reattachment included poor preoperative vision,
      extension of the retinal detachment to the macula (P < 0.05) and grades B, C or D
      proliferative vitreoretinopathy (P < 0.01). In addition to the above factors,
      eyes with vitreous loss, anterior chamber lens, aphakia and a larger extent of
      the retinal detachment had a poor visual outcome. CONCLUSION: Most aphakic or
      pseudophakic retinal detachment can now be reattached with either scleral or
      vitreo retinal surgery. The main difficulties are the localisation of the breaks
      and the treatment of PVR. Indirect ophthalmoscopy associated with vitrectomy does
      well in cases of an opacified posterior capsule. In cases of severe PVR long term
      internal tamponade either with C3F8 or silicone oil improves anatomical results
      but the functional results remain inferior.

PMID- 9237131
TI  - Holmium YAG laser sclerostomy ab externo for refractory glaucoma.
AB  - Ab externo thermal sclerostomy was performed with the holmium YAG (thulium,
      holmium, chromium-doped YAG crystal) laser in 21 eyes of 20 patients with
      refractory glaucoma. We used either the 5-fluorouracil (5-FU) or mitomycin C
      (MMC) antimetabolites in all cases. The rate of intraocular pressure (IOP)
      control defined as IOP < 21 mmHg regardless of whether antiglaucoma medication
      was applied postoperatively) was estimated by the life-table methods of Kaplan
      Meier. The postoperative IOP control rate was 47.1% in the MMC-treated group at
      57 months, and 14.3% in the 5-FU-treated group at 52 months. There were
      statistically significant differences in success rates between the MMC- and 5-FU
      treated groups. We observed no clinically significant complications except excess
      filtration associated with a shallow anterior chamber in one case. This procedure
      is thought to have several advantages over more conventional filtration surgery;
      the operation time is shorter, and there is no need for intraocular manipulation,
      which means conjunctival trauma is minimal. However, the IOP control rate was
      substantially lower than that achieved via conventional trabeculectomy. Our
      results suggest that the selection of patients and the use of MMC is an important
      factor in maintaining successful filtration.

PMID- 9237132
TI  - Preoperative testing practice in healthy cataract surgery patients. Results of a
      survey of ophthalmologists in Barcelona, Spain. Barcelona I-PORT Investigators.
AB  - AIMS/BACKGROUND: Many preoperative ophthalmic and medical tests lack proven
      effectiveness in the evaluation of cataract surgery patients. Variation in use
      has been described in the USA, but little information is available for countries
      with different health systems. The objectives of the study were to assess
      variation in ophthalmologists' use of preoperative testing on cataract surgery
      patients and to identify ophthalmologists' characteristics associated with it.
      METHODS: A postal survey was made in a representative sample (response rate of
      70%) of the Barcelona Medical Association of Ophthalmologists performing cataract
      surgery during 1993 (N = 89). The questionnaire included information about common
      preoperative, intraoperative and postoperative practice and sociodemographic and
      professional data. Appropriateness of preoperative ophthalmic tests was
      classified in 3 levels (indicated tests, tests with unproven benefit, and non
      indicated tests) according to recommendations of the Cataract Management
      Guideline Panel [1] and the American Academy of Ophthalmology Preferred Practice
      Pattern [2]. RESULTS: Almost all the ophthalmologists reported performing Fundus
      exam plus A-scan in the preoperative evaluation of cataract surgery patients
      (indicated tests). Up to 20% reported performing 'frequently' or 'always' some
      non-indicated or unproven benefit ophthalmic tests. Additionally, an average of 7
      medical tests were 'routinely' included. Private practice and cataract
      subspeciality were the ophthalmologists' characteristics more frequently
      associated with the use of inappropriate ophthalmic tests (p < 0.05).
      CONCLUSIONS: In Barcelona, Spain, some ophthalmic tests of unproven effectiveness
      are frequently performed preoperatively on cataract surgery patients without
      ocular comorbidity. Also, a generalized utilization of several medical tests was
      reported. There is potential for some cost containment and more appropriate care
      of cataract patients without diminishing the quality of care, in a location with
      low surgery rates.

PMID- 9237133
TI  - The utilization of a biological adhesive for wound treatment: comparison of
      suture, self-sealing sutureless and cyanoacrylate closure in the tensile strength
      test.
AB  - We produced a measurement apparatus for testing the tensile strength of wounds
      during cataract surgery, and tested the tensile strength of treated wounds
      including wounds sutured with various methods, non-sutured and wounds treated
      with various bio-tissue adhesives. METHODS: In cataract surgery on white rabbits
      eyes, a corneoscleral incision 5 mm in length was made 2.5 mm from the limbus
      corneae, and entry into the anterior chamber was obtained 0.5 mm to the clear
      cornea. After treatment for closure, the corneoscleral piece was subjected to the
      tensile strength test. RESULTS: The tensile strengths just after surgery were (1)
      0 gf/mm2 after self-sealing sutureless closure; (2) 114 gf/mm2 after vertical
      suture closure (one stitch with 10-0 nylon); (3) 125 gf/mm2 after horizontal
      suture closure (one stitch with 10-0 nylon); (4) 143 gf/mm2 after infinity suture
      closure (with 10-0 nylon); (5) 112 gf/mm2 after fibrin glue (Beriplast P)
      application (instilled on the surface of scleral incision); (6) 121 gf/mm2 after
      fibrin glue application (glued on corneoscleral wound); (7) 131 gf/mm2 after
      cyanoacrylate closure (instilled on the surface of scleral incision); (8) 139
      gf/mm2 after cyanoacrylate closure (glued on corneoscleral wound). The respective
      strengths at four days after surgery were: (1) 86; (2) 131; (3) 137; (4) 175; (5)
      109; (6) 43; (7) 138; and (8) 108 gf/mm2. At 28 days after surgery, the
      respective strengths were (1) 164; (2) 167; (3) 184; (4) 209; (5) 322; (6) 195;
      (7) 251; and (8) 175 gf/mm2. CONCLUSION: The use of fibrin glue in treatment of a
      wound in cataract surgery is beneficial in assisting this treatment.

PMID- 9237134
TI  - Anomalous intraocular pressure changes in Chagas' disease elicited by postural
      test.
AB  - We compared the effects of postural changes on intraocular pressure, systemic
      blood pressure, and pupil size with and without induced mydriasis in 15 chronic
      chagasic patients and 20 healthy age-matched controls. The chagasic patients
      showed a marked fall in intraocular pressure on rising. However, systemic
      systolic blood pressure changes and pupil size in patients did not differ from
      those measured in controls. Our findings may be explained by an alteration in the
      autonomic ocular system that regulates homeostasis of ocular pressure and the
      probable existence of a baroreceptor arc-reflex that restores the equilibrium of
      sudden changes in the intraocular pressure.

PMID- 9237135
TI  - Report of a case of aggressive cytomegalovirus retinitis in an infant with AIDS.
AB  - A case of aggressive cytomegalovirus retinitis is reported in an infant with
      acquired immunodeficiency syndrome. Intravenous treatment with ganciclovir did
      not control the infection. The combination of ganciclovir and foscarnet was
      needed to obtain a complete response.

PMID- 9237136
TI  - Plasmacytoma of the eye and orbit.
AB  - BACKGROUND: Plasmacytomas of the ocular and adnexal tissue are rare. The
      variation in their clinical manifestations and potential association with
      multiple myeloma are not well appreciated. METHODS: We reviewed the clinical
      features and laboratory data of five cases of plasmacytoma involving the eye and
      orbit. RESULTS: Plasmacytomas involved the conjunctiva in one case, the orbit in
      three cases, and the iris in one case. Plasmacytoma was the solitary plasma cell
      neoplasm in a patient with a conjunctival lesion and another patient with an
      orbital lesion. Two other patients who developed plasmacytomas of the orbit and
      iris, respectively, had a known history of multiple myeloma. An orbital
      plasmacytoma preceded the onset of systemic plasma cell neoplasia in the final
      patient. CONCLUSION: Plasmacytomas of the eye and orbit are rare. They may or may
      not be associated with multiple myeloma.

PMID- 9237138
TI  - In vitro failure load of metal-collar margins compared with porcelain facial
      margins of metal-ceramic crowns.
AB  - PURPOSE: This in vitro study compared the load necessary to cause porcelain
      failure on traditionally fabricated metal-ceramic crowns cemented to metal tooth
      analogs with two different types of margins. MATERIAL AND METHODS: Metal-ceramic
      crowns were constructed with either metal facial collars or porcelain facial
      margins. The metal tooth analogs were embedded in polymethyl methacrylate resin
      blocks, so that a load applied to the lingual surface compressed the facial
      margins. Increasingly greater loads were applied to specimens until failure
      occurred and the failure load values of all specimens were statistically
      evaluated. RESULTS: The load required to cause porcelain fracture in the crowns
      with porcelain facial margins was statistically significantly greater than the
      load required to cause porcelain fracture for crowns with metal collars (p <
      0.02).

PMID- 9237137
TI  - Basic fibroblast growth factor mRNA, bFGF peptide and FGF receptor in epiretinal
      membranes of intraocular proliferative disorders (PVR and PDR).
AB  - Basic fibroblast growth factor (bFGF) has been shown to be involved in epiretinal
      membrane formation in proliferative vitreoretinal disorders. However, up to now,
      little knowledge exists; as to the actual cellular source of this potent mitogen.
      We examined 20 epiretinal membranes from patients with proliferative diabetic
      retinopathy (PDR) (n = 12) and proliferative vitreoretinopathy (PVR) (n = 8) for
      the presence of bFGF peptide, fibroblast growth factor receptor-1 (FGFR-1) and
      bFGF messenger ribonucleic acid (mRNA). Using a specific antibody, we detected
      bFGF peptide in most (8/10) examined PDR membranes and in all (8/8) PVR
      membranes. Moreover, we found positive staining for the corresponding receptor.
      Local production of bFGF in epiretinal membranes was confirmed by nonisotopic in
      situ hybridisation for bFGF mRNA in some (4/7) examined PDR membranes and some
      (3/4) examined PVR membranes. All membranes which contained bFGF mRNA were also
      positive for bFGF peptide. In conclusion, bFGF is produced and stored in
      epiretinal membranes. Together with the corresponding receptor, bFGF may play a
      role in the auto- and paracrine control of the proliferative processes at the
      vitreoretinal interface.

PMID- 9237139
TI  - An in vitro evaluation of a carbon fiber-based post and core system.
AB  - STATEMENT OF PROBLEM: A self-contained post and core system, Composipost,
      comprising an epoxy-based carbon fiber post, a composite core material, and a low
      viscosity Bis-GMA bonding resin, has recently been marketed for the restoration
      of pulpless teeth. PURPOSE: This study compared the in vitro performance and the
      failure characteristics of the Composipost system against existing post and core
      combinations. MATERIAL AND METHODS: Using extracted human teeth, three post and
      core test groups and one control group were then tested to failure with an
      obliquely applied compressive load at 130 degrees in a Hounsfield testing-machine
      with a crosshead speed of 5 cm/minute. RESULTS: The mean stress values at failure
      (MNm.2) with standard deviations for each group were as follows: Composipost
      system 8.89, SD 2.40; stainless steel post and composite core 14.18, SD 3.49;
      cast gold alloy post and gold alloy core 15.25, SD 4.07; and endodontically
      treated tooth only 24.84 SD 4.58. CONCLUSION: The specimens restored with the
      Composipost system exhibited inferior strength properties in comparison to the
      other post and core systems tested (p < 0.01). Teeth without post and core
      foundations tested significantly stronger than the other comparison groups (p <
      0.01).

PMID- 9237140
TI  - Root reinforcement with a resin-bonded preformed post.
AB  - PURPOSE: This study evaluated the ability of resin-bonded posts to reinforce
      teeth that are structurally weak in the cervical area against fracture. MATERIAL
      AND METHODS: Forty canine roots were endodontically treated and randomly
      distributed into four groups of 10. Parallel-sided preformed posts were cemented
      into the roots of these teeth after their crowns were removed. The cervical third
      of the canals were flared to simulate teeth weakened in this area as a result of
      caries or endodontic therapy. Three resin cements and a zine-phosphate cement,
      which was used as the control, were used to secure the posts into the roots.
      Cemented posts were loaded in an Instron testing machine with a gradually
      increasing force at a 60-degree angle to the long axis of the root until the root
      fractured. RESULTS: Roots in which the posts were cemented with Panavia were
      significantly more resistant to fracture than those where zinc phosphate was used
      (p < 0.05). Because of the inability to determine exactly the point of failure of
      the zinc-phosphate cement, no statistically significant difference was found when
      compared with the other two resin cements (ANOVA and Student-Newman-Keuls test).

PMID- 9237141
TI  - A randomized clinical trial of two basic removable partial denture designs. Part
      II: Comparisons of masticatory scores.
AB  - STATEMENT OF PROBLEM: There is no known data on the functional efficacy of
      different removable partial denture designs. PURPOSE: This randomized clinical
      trial compared the masticatory performance of two commonly used designs in 118
      patients who needed a unilateral or bilateral mandibular partial denture.
      MATERIAL AND METHODS: One half of the patients received a partial denture with
      distal occlusal rests and cast circumferential clasps and the other half a
      partial denture with mesial rests and I-bar cast clasps. The left side, right
      side, and swallowing threshold masticatory tests were made with peanuts and
      carrots before treatment and 16 weeks after the prosthesis insertion (baseline)
      and thereafter at 6, 18, 36, and 60 months. RESULTS: Masticatory scores at entry
      were higher in the circumferential design group, but the only significant (p <
      0.05) difference was found in the right side carrot performance. Both groups
      realized significant improvements (p < 0.001) in all performance scores with
      partial dentures. Mean improvements of 24.7 with peanuts and 35.8 with carrots in
      the right side performance scores and 19.0 in the swallowing threshold score with
      peanuts in the bar design group were significantly higher (p = 0.017) than the
      respective mean improvements of 15.9, 21.4, and 5.6 in the circumferential design
      group. However, no significant differences were found between the two groups for
      any of the 10 performance scores at baseline. CONCLUSIONS: Despite some
      performance differences at entry, the mean performance scores for the two groups
      became similar at baseline and at subsequent intervals.

PMID- 9237142
TI  - Effect of friction coefficient on Akers clasp retention.
AB  - STATEMENT OF PROBLEM: Retentive force control of clasp retainers is one of the
      most essential factors for the successful function of removable partial dentures.
      However, it is not yet known how the friction coefficients differ among restored
      abutments and clasp materials, and how the friction coefficients affect the
      retention of clasps. PURPOSE: The purposes of this study were to clarify the
      friction coefficients among restored abutments and clasp materials and to
      estimate the effect of friction coefficients on the retention of clasps. MATERIAL
      AND METHODS: The coefficients of static friction between three clasp materials
      (type IV gold, high Pd, and cobalt-chromium [Co-Cr] alloys) of two surface
      treatments (polished and sandblasted) and four abutment materials (human enamel,
      porcelain, type IV gold, and high Pd alloys) were evaluated under three
      conditions (dry, wet with water, and wet with saliva), and theoretically, the
      effect of the friction coefficients on clasp retention was estimated. RESULTS:
      The friction coefficients under various conditions ranged from 0.08 (polished Co
      Cr clasp on type IV abutment in dry condition) to 0.37 (sandblasted Co-Cr clasp
      on high Pd abutment in dry condition). The theoretical estimation clarified that
      the retentive force of the clasp was linear to the friction coefficient.
      CONCLUSION: The retentive force increased linearly with increasing friction
      coefficient between abutment material and clasp material according to the newly
      developed formula. This study suggested that clasp designs should be changed
      depending on abutment materials.

PMID- 9237143
TI  - The implant-supported prosthesis for the edentulous arch: design considerations.
AB  - STATEMENT OF PROBLEM: Edentulous patients who require implant-supported
      prostheses have diverse jaw anatomy and functional, esthetic, and economic
      concerns. Four main prosthetic designs have been used to meet these needs.
      PURPOSE: In this article, the fixed ceramometal, fixed detachable, overdenture,
      and fixed removable prostheses are discussed with emphasis on indications and
      limitations. An in-depth diagnosis and informed treatment planning will maximize
      implant success and patient satisfaction.

PMID- 9237144
TI  - Implant reconstruction in the posterior mandible: a long-term retrospective
      study.
AB  - STATEMENT OF PROBLEM: Because there is a lack of long-term data, it is unclear
      whether the determinants of implant and prosthesis survival include the location,
      angle, design, or number of implants and use of prosthesis cantilevers. PURPOSE:
      This retrospective study evaluated the long-term outcome, determinants of
      outcome, and the type and prevalence of prosthetic complications in a series of
      patients treated consecutively with Branemark implants in the partially
      edentulous posterior mandible. MATERIAL AND METHODS: A total of 392 consecutively
      placed Branemark implants were inserted in 152 partially edentulous patients and
      restored with 56 single-tooth and 168 fixed partial dentures restorations.
      RESULTS: The cumulative success rates of implants and prostheses were 89.0% +/-
      0.03% and 81.9% +/- 0.03%, respectively, at 6 years, with no further decrease in
      success noted during the remainder of the 10-year study. Significantly fewer
      major complications were found in prostheses supported by one or more implants,
      located exclusively in premolar sites, versus prostheses supported by either
      molar implant(s) or both premolar and molar implants. In single-tooth
      restorations, fewer major complications were seen in the cemented restorations,
      compared with the screw retained. CONCLUSION: The results were strongly
      influenced by the phase of experience.

PMID- 9237145
TI  - Cement removal from restorations luted to titanium abutments with simulated
      subgingival margins.
AB  - STATEMENT OF PROBLEM: The process of removing excess cement from subgingival
      margins after cementation of restorations to implant abutments may lead to
      scratching of the abutments or incomplete cement removal. PURPOSE: The purpose of
      this study was to investigate and to compare the surfaces of abutments after the
      removal of three cements (glass ionomer, resin, and zinc phosphate) by use of
      three instruments (gold coated scaler, rigid plastic scaler, and stainless steel
      explorer). MATERIAL AND METHODS: Six investigators removed zinc phosphate, glass
      ionomer, and resin cements with explorers, gold coated scalers, and rigid plastic
      scalers with a model simulating clinical conditions. The surface of Branemark
      abutments with cemented restorations were examined with a microscope at 20x for
      scratches and cement remnants. RESULTS: Statistical analysis of the results were
      inconclusive about which combination of instrument and cement worked most
      effectively. CONCLUSION: A surprising amount of cement remnants and scratching of
      abutments was observed. Although the six investigators were experienced in
      prosthodontic and implant procedures, there was variation in the results of their
      cement removal.

PMID- 9237146
TI  - Mandibular rest position and electrical activity of the masticatory muscles.
AB  - STATEMENT OF PROBLEM: The determination of a correct vertical dimension of
      occlusion is a critical procedure in clinical dentistry. PURPOSE: The objectives
      of this study were to analyze the relation between mandibular rest position and
      electrical activity of masticatory muscles and to compare clinical and
      electromyographic rest position in subjects with different vertical facial
      morphologic features. MATERIAL AND METHODS: Clinical rest position and
      electromyographic rest position were investigated in 40 subjects.
      Electromyographic rest position ranged from 0.4 to 12.7 mm (average 7.7 +/- 2.7
      mm). Clinical rest position ranged from 0.1 to 4.4 mm (average 1.4 +/- 1.1 mm).
      The average difference between electromyographic rest position and clinical rest
      position was 6.3 +/- 2.5 mm (range 0.3 to 10.3 mm). Sixteen subjects were
      selected according to the Frankfort mandibular plane angle and separated in two
      groups having a mandibular plane angle > or = 28 degrees. RESULTS: Rest position
      was significantly greater (p < 0.05) in the low-angle group (2 +/- 1.3 mm) than
      in the high angle group (0.8 +/- 0.8 mm). Electromyographic rest position did not
      differ between subjects with different facial morphologic features (8.1 +/- 1.7
      mm low-angle group; 7.6 +/- 4.1 mm high angle group). By varying the vertical
      dimension millimeter by millimeter, masseter and anterior temporal
      electromyographic activity demonstrated a considerable decrease over an
      interocclusal distance of 3 to 4 mm. Further mandibular opening up to 18 mm
      corresponded to small changes in postural activity. CONCLUSION: This study
      suggests that a jaw posture with a few millimeters of interocclusal distance
      involves a great reduction of masticatory muscle activity.

PMID- 9237148
TI  - Burning mouth syndrome: a review of etiologies.
AB  - STATEMENT OF PROBLEM: Dental practitioners occasionally have patients present
      clinically with a history of chief complaint of burning and painful sensations in
      the oral cavity. Often the patient demonstrates clinically normal mucosa, which
      can make formulating a diagnosis challenging. This scenario, has been referred to
      as burning mouth syndrome, a multifactorial syndrome. PURPOSE: The purpose of
      this article is to present a review of etiologic factors and clinical
      implications related to the condition of burning mouth syndrome.

PMID- 9237147
TI  - Annual review of selected dental literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 9237150
TI  - Unilateral rotational path removable partial dentures for tilted mandibular
      molars: design and clinical applications.
AB  - This article describes the design of a unilateral rotational path removable
      partial denture to restore a single edentulous space with a tilted mandibular
      molar. It is modified from an original bilateral rotational path design and
      consists of several components, which are (1) the rotation axis, (2) the long
      occlusal rest, (3) the short bracing arms, (4) the rigid retainer and extended
      proximal plates, (5) the conventional direct retainer assembly, and (6) optional
      auxiliary rest. The stability and retention of the denture are controlled
      anteriorly by the buccal retentive clasp and lingual guide plate of the
      conventional direct retainer, and posteriorly by the rigid retainer and its
      buccally and lingually extended proximal plates. The clinical results of the
      dentures used in strictly selected situations are excellent; however, it is
      emphasized that a unilateral denture is only an alternative rather than a routine
      application. The risk of accidental aspiration is also of concern.

PMID- 9237149
TI  - An alternative method for direct custom tray construction using a visible light
      cured resin.
AB  - The use of a properly made tray is highly desirable for impression making. To
      avoid the extra time required for tray fabrication, the alternative techniques of
      the putty wash or "reline" technique and intraoral fabrication of a custom tray
      by relining a stock tray with self-curing resin are proposed. This article
      illustrates a new technique of direct custom tray fabrication used for impression
      making for fixed prosthodontics. The proposed technique allows the direct
      fabrication of custom trays with light-cured resin and is time-saving, efficient,
      and inexpensive.

PMID- 9237151
TI  - Stabilization investment template for direct casting connection of implant
      framework segments.
AB  - This article presents a procedure whereby a template made of casting investment
      is used to stabilize a sectioned implant framework that has been adapted in a
      passive relationship to the implant analogs in a corrected master cast. The
      joints in the sectioned framework are filled with wax, sprues attached, and the
      template and sectioned framework are invested in a casting ring. When the casting
      procedure is completed, the framework will be reconnected by direct metal
      casting.

PMID- 9237152
TI  - Single-tooth implants: a procedure to make a precise, flexible gingival contour
      on the master cast.

PMID- 9237153
TI  - Pterygoid hamulus bursitis: one cause of craniofacial pain.

PMID- 9237154
TI  - Detection of K-ras point mutation by in situ PCR in cell suspensions: comparison
      of the indirect and direct methods.
AB  - In situ PCR is a new technique for the localization of low copy number sequences.
      We report here a method for the in situ visualization of a point mutation in K
      ras codon 12 by indirect in situ PCR. Twenty-five primers were examined to select
      mutant-specific primers. Harvested cell lines were fixed and suspended in PCR
      mixture. Forty cycles of PCR in cell suspension was performed in a thermal cycler
      using a hot start method. Cells were cytocentrifuged onto slides, and post
      fixation was performed. The specimens on the slides were then hybridized with a
      digoxigenin-labeled probe, followed by color reaction. Both Calu-1 (mutated: TGT)
      and NCI-H460 (wild type: GGT) cells had strong hybridization signals in the
      nuclei with general primers. But with mutant-specific primers, only Calu-1 cells
      had hybridization signals. No signal was observed without primers or Taq DNA
      polymerase. Southern blotting of the same preparation confirmed desired
      amplification. We also applied direct in situ PCR, but this method failed to
      detect the point mutation. We conclude that our indirect in situ PCR method shows
      the feasibility of in situ identification of single cells carrying point
      mutations.

PMID- 9237156
TI  - Serum hepatocyte growth factor/scatter factor levels in small cell lung cancer
      patients.
AB  - Serum hepatocyte growth factor/scatter factor (HGF/SF) levels were measured in 25
      patients with small cell lung cancer (SCLC), 16 patients with benign lung
      diseases and 15 healthy subjects with an enzyme-linked immunosorbent assay. The
      patients with SCLC did not have bacterial or interstitial pneumonia. Patients
      with benign lung diseases included eight with bacterial pneumonia, three with
      interstitial pneumonia, and five with benign lung tumor. Serum HGF/SF levels were
      significantly higher in patients with SCLC (mean +/- S.D.: 0.40 +/- 0.17 ng/ml)
      than in healthy subjects (0.26 +/- 0.093 ng/ml) (P = 0.0083). Patients with
      bacterial pneumonia had significantly higher serum HGF/SF (0.52 +/- 0.19 ng/ml)
      than did those with benign lung tumors (0.27 +/- 0.058 ng/ml) and healthy
      subjects (P = 0.013 and P = 0.0019, respectively). By clinical stage of SCLC,
      HGF/SF levels were 0.34 +/- 0.12 and 0.47 +/- 0.20 ng/ml in patients with limited
      disease and extensive disease, respectively; this difference was not significant
      (P = 0.080). Although serum HGF/SF levels were increased in patients with SCLC,
      this increase might not have been related to tumor burden.

PMID- 9237155
TI  - Levels of plasminogen activator inhibitor type 1 and urokinase plasminogen
      activator receptor in non-small cell lung cancer as measured by quantitative
      ELISA and semiquantitative immunohistochemistry.
AB  - The components of the plasminogen activation system have been reported to have
      prognostic impact in several cancer types, e.g. breast-, colon-, gastric- and
      lung cancer. Most of these studies have used quantification by enzyme-linked
      immunosorbent assay (ELISA) on tumour tissue extracts. However, results in non
      small cell lung cancer (NSCLC) studies obtained by quantitative ELISA and
      semiquantitative immunohistochemistry differ. If the prognostic value of the
      components of the plasminogen activation system is to be exploited clinically in
      the future, it is important to choose an easy and valid methodology. In the
      present study we investigated levels of plasminogen activator inhibitor type 1
      (PAI-1) and urokinase plasminogen activator receptor (uPAR), as quantitated by
      ELISA in tumour extracts from 64 NSCLC patients (38 squamous cell carcinomas, 26
      adenocarcinomas), and compared them to staining intensity as semiquantitated by
      immunohistochemistry for PAI-1 and uPAR on corresponding cryostat sections. A
      significant association (r = 0.49, P < 0.0001) was found between the PAI-1 levels
      measured by ELISA and semiquantitated by immunohistochemistry. No association was
      found for uPAR. When correlating levels of PAI-1 and uPAR determined by ELISA and
      immunohistochemistry, respectively, to survival status, no significant
      correlation was found for any of the subgroups. At present neither of the methods
      examined in the present study can be recommended as superior for quantitating PAI
      1 and uPAR with the aim of predicting prognosis. In conclusion, a larger
      comparative study is needed to clarify the relationship between ELISA and
      immunohistochemical results, before a methodology for clinical use can be chosen
      in non-small cell lung cancer.

PMID- 9237157
TI  - The trends in histological types of lung cancer during 1980-1988, Guangzhou,
      China.
AB  - Five thousand five hundred and forty six cases of all lung cancer patients who
      died during 1980-1988 in Guangzhou, China were investigated retrospectively with
      a standardized 31-item questionnaire administered to their next of kin. The data
      of 1093 lung cancer patients(20%, 1093/5546) who had a histological record was
      analyzed to investigate the changes in histological types and the possible
      etiologic causes. The difference between the lung cancer deaths with and without
      histological record is not significant in age, location (peripheral or central)
      of tumour and status of occupation (P > 0.05), but the difference in sex is
      significant (P < 0.01). We analyzed the data of 1093 cases by sex and by 3-year
      period. There had been a shift in the histology pattern with an increase in the
      percentage of adenocarcinoma (P = 0.0011) and a decrease in percentage of
      squamous cell carcinoma (P = 0.0027) in males, inversely, there has been an
      absolute and a relative decrease of percentage in adenocarcinoma in females (P =
      0.0028). The percentage of smokers, age of starting to smoke and type of tobacco
      smoking were nearly constant in both sexes during the studied periods. The pack
      years of smoking decreased in males (P = 0.0396), and seemed increase in females
      (P = 0.1576, no significance). The analysis of occupation and dietary habits
      among 5546 cases were performed. The proportion of housewives decreased with time
      (P < 0.001) while the percentage of chemists in females increased (P < 0.001)
      with time. The dietary habits are changing with an increase in roast food intake
      for males (P = 0.0055) and in vegetable intake for males (P < 0.0001), females (P
      < 0.0001), and for patients with lung squamous cell carcinoma and adenocarcinoma
      in both sexes (P < 0.001). Perhaps the changes in pack-years of smoking may be
      responsible for the percentage change of lung cancer histological types observed
      in our study. The role that changes in dietary habits and status of occupations
      play in the changing trends of lung cancer histological types in our study need
      further study.

PMID- 9237158
TI  - Intensification of 111In-DTPA-octreotide scintigraphy by means of pretreatment
      with cold octreotide in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced
      with 111In-DTPA-octreotide scintigraphy. Although this technique is currently
      employed for staging and follow-up of neuroendocrine tumors of the
      gastrointestinal tract, its role in the clinical work-up of SCLC is at present
      under discussion. A better imaging contrast is desirable and recent reports
      suggest that this aim could be achieved by pretreatment with cold octreotide.
      Here we report on the results of 111In-DTPA-octreotide scintigraphy in 12 SCLC
      patients carried out before and after octreotide treatment. The patients were
      treated for 7 days with octreotide 200 micrograms three times a day s.c. Uptake
      was studied at 5 h with whole body planar and SPET imagings. In all cases
      studied, pretreatment with octreotide was followed by enhancement of tumor
      imaging. In one patient a better contrast of the lesions was found at the
      parenchymal and mediastinal levels as well as at brain level, allowing a clear
      definition of otherwise questionable metastases. After octreotide treatment, a
      decrease in background uptake in the subdiaphragmatic area was observed in most
      cases, allowing a better imaging of liver metastases. The enhancement effect was
      confirmed by semiquantitative analysis of scintigraphic uptake. Taken together,
      our results seem to indicate that cold octreotide enhancement can improve 111In
      DTPA-octreotide imaging and optimize its clinical role in SCLC.

PMID- 9237159
TI  - Distribution of 99mTc colloid in the thoracic cavity of patients with malignant
      pleural effusions.
AB  - The distribution of labelled tetracycline in the pleural space of patients with
      malignant effusions has been shown not to improve significantly after rotating
      the patient. As the number of patients was small, we investigated the
      distribution of an inert radio labelled colloid (99mTc) in the pleural space
      directly after administration and after 1 h of rotation. Nineteen examinations
      were performed in 18 patients with malignant pleural effusions. In two out of 19
      examinations (11%) a considerable improvement in distribution was observed and
      some improvement was found in five out of 19 examinations (26%). The relation
      between distribution and the effect of tetracycline pleurodesis at 12 weeks and
      the identification of patients for whom pleurodesis would not be successful were
      also studied. The analysis of the distribution and outcome of pleurodesis was
      hampered by the fact that additional anti tumour treatments were given after
      pleurodesis. CONCLUSIONS: The influence of rotation on the distribution of 99mTc
      colloid in the pleural space is minimal and indicates that this could be omitted.
      A distribution pattern predictive of failure of pleurodesis could not be
      identified in this study.

PMID- 9237160
TI  - Superior sulcus tumor (SST): management at the Institute of Oncology in
      Ljubljana, Slovenia, 1981-1994.
AB  - During the 14-year period under study, 48 patients with SST were treated at the
      Institute of Oncology in Ljubljana, Slovenia. There were 46 males and two
      females, aged 29-88 years (median, 60 years). Of 37 cytologically or
      histologically confirmed tumors, 12 were squamous, eight large-cell, one small
      cell, eight adeno, and eight unclassified carcinomas. Performance status
      (Karnofsky) was assessed as > 90 in eight, 70-90 in 31 and < 70 in nine patients.
      The duration of symptoms before diagnosis ranged from 1 to 36 months (median, 5
      months). All patients had pain, while six also had hemophthysis, 14 Horner's
      syndrome, and four Horner's syndrome and upper limb paresis. Before the first
      chest X-ray, 19 patients- were treated for shoulder pain by different
      specialists. Apical tumor infiltration only on the chest X-ray was found in 13,
      destruction of the ribs in 31, and destruction of the ribs and vertebral bodies
      in four patients. Treatment was as follows: radiotherapy in 39 patients (22 with
      radical, 17 with palliative dose), a combination of surgery and radiotherapy in
      seven, radiotherapy and chemotherapy in one, and symptomatic therapy alone in one
      patient. One- and four-year survival of all treated patients was 27% and 11%,
      respectively. One of the seven patients operated on survived for 44 months, and
      2/39 irradiated ones survived for 37 and 56 months, respectively, while others
      died within 24 months from diagnosis. In 81% of patients the pain was subdued
      after radiotherapy. The disease-specific survival of all patients included in the
      follow-up correlated with performance status and M stage, while that of those
      treated by irradiation alone correlated with tumor dose (P < 0.05).

PMID- 9237161
TI  - Modified weekly regimen with vinorelbine as a single agent in unresectable non
      small cell lung cancer.
AB  - After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL)
      dose, a multicenter phase II trial of a modified weekly VRL treatment protocol
      (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer
      (NSCLC) was designed to determine its clinical activity, toxicity, and survival
      of treated patients. As myelotoxicity frequently precludes the administration of
      VRL, by suppressing the dose that would correspond to day 15 of a weekly
      protocol, we allowed bone marrow recovery to take place and avoided the
      administration of the drug at the nadir of the cycle. The trial included 71
      consecutive, previously untreated patients with unresectable and measurable
      disease. A total of 297 three-week treatment courses were administered with an
      average of 4 courses per patient (range 1-11). Results showed that in spite of
      attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL
      treatment regimen has a low level of activity (7.5% response rate) in NSCLC.
      Although a more tolerable level of toxicity is achieved, in order to maintain its
      antitumor activity, the recommended dose of VRL when given alone for NSCLC
      treatment (30 mg/m2/weekly) should not be decreased.

PMID- 9237162
TI  - Primary lung liposarcoma.
AB  - Liposarcoma of the lung is extremely rare with only 11 cases previously reported.
      A case of a locally advanced pulmonary pleomorphic liposarcoma in a 49-year-old
      male is presented. Surgery was performed but radical resection was not possible.
      Post-operative radiotherapy (40 Gy) was given concurrently with cisplatin (12.5
      mg daily for 10 days). A partial response of short duration was obtained. The
      patient died 8 months following surgery with disseminated disease. Based on
      reports in the literature, liposarcoma of the lung must be classified as an
      aggressive highly metastatic disease responding poorly to both chemotherapy and
      radiotherapy.

PMID- 9237163
TI  - Assays for investigating transcription by RNA polymerase II in vitro.
AB  - With the availability of the general initiation factors (TFIIB, TFIID, TFIIE,
      TFIIF, and TFIIH), it is now possible to investigate aspects of the mechanism of
      eukaryotic messenger RNA synthesis in purified, reconstituted RNA polymerase II
      transcription systems. Rapid progress in these investigations has been spurred by
      use of a growing number of assays that are proving valuable not only for
      dissecting the molecular mechanisms of transcription initiation and elongation by
      RNA polymerase II, but also for identifying and purifying novel transcription
      factors that regulate polymerase activity. Here we describe a variety of these
      assays and discuss their utility in the analysis of transcription by RNA
      polymerase II.

PMID- 9237164
TI  - Analysis of open complex formation during RNA polymerase II transcription
      initiation using heteroduplex templates and potassium permanganate probing.
AB  - Open complex formation precedes initiation of transcription by RNA polymerases.
      In the analysis of transcription initiation from eukaryotic class II promoters,
      we have used promoter DNA structures that represent intermediates in open complex
      formation. We describe the preparation and isolation of heteroduplex promoter
      fragments. Probes containing these DNA structures have a general application in
      the study of proteins binding to junctions of double- and single-stranded DNA.
      Such proteins play important roles not only in the regulation of RNA synthesis
      but also in processes like repair, replication, and recombination of DNA. In
      addition, a protocol is provided for a rapid and quantitative assay for open
      complexes and transcription bubbles using potassium permanganate as a chemical
      probe for single-stranded regions in DNA.

PMID- 9237165
TI  - Yeast RNA polymerase II transcription reconstituted with purified proteins.
AB  - Protocols are presented for the preparation of a fully defined yeast RNA
      polymerase II transcription system, consisting of essentially pure TFIIB, -E, -F,
      and -H, TATA-binding protein, RNA polymerase II, and mediator of transcriptional
      regulation. This system, comprising 44 polypeptides, is able to initiate
      transcription at any of a dozen yeast and mammalian promoters thus far tested and
      responds to a variety of transcriptional activator proteins.

PMID- 9237166
TI  - Functional analysis of TFIID-activator interaction by magnesium-agarose gel
      electrophoresis.
AB  - The general transcription factors TFIID and TFIIA are critical for the
      recognition of promoter start sites and mediate the stimulatory effect of some
      transcriptional activators. The regulation of TFIID binding to promoter DNA by
      activators and coactivators can be studied using a modified gel electrophoresis
      mobility shift assay (EMSA). TFIID is a multiprotein complex that consists of the
      TATA binding protein (TBP) and TBP associated factors (TAFs). TBP is a sequence
      specific DNA binding protein that binds in the minor groove and introduces an
      energetically unfavorable bending angle of 100 degrees in the DNA. The activated
      preinitiation complex consists of TAFs, TBP, TFIIA, multiple activators, and
      approximately 200 bp of promoter DNA. The large mass and DNA distortions of the
      preinitiation complex preclude the use of conventional low ionic strength
      polyacrylamide gel EMSA for analysis. These large complexes can be analyzed by
      EMSA in agarose gels that contain magnesium ion. The Mg-agarose EMSA is a simple
      system useful for resolution of large multiprotein complexes that may introduce
      distortions in linear DNA. Important parameters are discussed so that this
      technique can be generally applied to other model activators.

PMID- 9237167
TI  - Small-scale density gradient sedimentation to separate and analyze multiprotein
      complexes.
AB  - The transcription factor TFIID is a multisubunit complex that is required for
      promoter recognition and accurate initiation of transcription by RNA polymerase
      II. To dissect the molecular architecture and the biochemical properties of
      TFIID, a small-scale density gradient sedimentation method is employed to
      separate related complexes through differences in their sedimentation properties.
      A small amount of starting material is sufficient to obtain readily assayable
      amounts of separated proteins after centrifugation for 8 to 12 h in a benchtop
      ultracentrifuge. Gradient fractions are analyzed by immunoblotting for the
      presence of specific components of TFIID. Sucrose gradient sedimentation is
      performed to separate a mixture of multiprotein complexes from a crude nuclear
      extract immunoprecipitation of the proteins present in each fraction with an anti
      TBP antibody reveals multiple TBP-containing complexes of different sizes.
      Density gradient sedimentation permits separation of specific components in a
      complex mixture and preserves activity, allowing functional assays.

PMID- 9237168
TI  - Purification of the transcription/repair factor TFIIH and evaluation of its
      associated activities in vitro.
AB  - We describe here the methodology developed in our laboratory to study the role of
      TFIIH, a multisubunit protein complex, in the various mechanisms of cell life:
      transcription, DNA repair, and cell cycle regulation. Protocols are given to
      purify TFIIH and to study its various enzymatic activities as well as its
      transcription and nucleotide excision repair activities.

PMID- 9237169
TI  - Methods for studying the biochemical properties of an Inr element binding
      protein: TFII-I.
AB  - Transcription initiation in eukaryotic mRNA coding genes is brought about by a
      host of general transcription factors, which assemble into a functional
      preinitiation complex (PIC) at the core promoter region, and gene-specific
      factors, which exert their effects on the rate and/or stability of the PIC. The
      core promoter region consists of a well-characterized TATA box and/or a less well
      characterized pyrimidine-rich initiator element (Inr). While the biochemical
      mechanisms of TATA-mediated transcription initiation are extensively studied and
      known to be directed by the TATA binding protein, the mechanisms via the Inr
      element are poorly understood, as several factors have been shown to bind to an
      Inr. Here, we describe the biochemical properties of an Inr binding protein, TFII
      I, employing the naturally occurring TATA-less but Inr-containing promoter
      derived from the T-cell receptor beta chain gene (V beta).

PMID- 9237170
TI  - Assaying CTD kinases in vitro and phosphorylation-modulated properties of RNA
      polymerase II in vivo.
AB  - The functional properties of RNA polymerase II are modulated by
      hyperphosphorylation of its unique C-terminal repeat domain (CTD). A number of
      enzymes with CTD kinase activity have been identified, and correlations between
      CTD phosphorylation and RNA polymerase II function have been made. Here we
      describe methods for assaying CTD kinases and for characterizing them
      enzymologically. In addition we present approaches for studying phosphorylation
      mediated behavior of chromosome-associated RNA polymerase II by using CTD
      directed, phosphorylation state-sensitive antibodies and in situ localization
      techniques. The methods described here should, in conjunction with genetic
      approaches, contribute to elucidating the physiological roles of CTD kinases.

PMID- 9237171
TI  - Analysis of transcription factor-mediated remodeling of nucleosomal arrays in a
      purified system.
AB  - An early step in a pathway leading to transcriptional initiation involves the
      rearrangement of chromatin at gene regulatory sequences. To study this process,
      we have developed a biochemical system analyzing the interactions between
      chromatin templates composed of arrays of positioned nucleosomes and sequence
      specific transcriptional activators. Here, a procedure is presented for the
      assembly of nucleosomal arrays on DNA fragments containing synthetic and natural
      gene sequences inserted within tandem repeats of sea urchin 5S rDNA. We also
      provide methods for the use of these templates in transcription factor-binding
      assays, as well as experimental data illustrating the efficacy of such analyses
      to uncover mechanisms directing factor-mediated nucleosome remodeling.

PMID- 9237172
TI  - Expression of inducible nitric oxide synthase in breast cancer correlates with
      metastatic disease.
AB  - Breast cancer is characterized by its ability to metastasize rapidly. Factors
      that might facilitate this metastatic potential include tumor vascularity. Nitric
      oxide (NO), a labile compound synthesized by NO synthase (NOS), is a major
      regulator not only of physiologic vascular tone but also of the abnormal
      vascularity associated with many tumors. To test whether NOS is expressed in
      primary breast tumors and whether its expression is associated with the presence
      of metastasis, we analyzed the expression of the inducible NOS in 22 primary
      breast tumors, and to investigate its association to other gene products related
      to the metastatic ability of tumor cells, we correlated the expression of the
      inducible NOS with the expression of the nm23 protein (the product of the
      putative antimetastatic gene nm23). We found a very strong correlation between
      the presence of NOS and axillary lymph node metastasis and between NOS and the
      absence of nm23 protein. These data suggest that NO synthesis and the resulting
      increase in blood flow to the tumor play a role in the facilitation of tumor
      metastasis.

PMID- 9237174
TI  - Diagnostic accuracy and key cytologic features of high-grade transitional cell
      carcinoma in the upper urinary tract.
AB  - This study examined the diagnostic accuracy of upper urinary tract cytology and
      defined key cytologic criteria by logistic regression analysis for the diagnosis
      of high-grade transitional cell carcinoma (TCC). The upper urinary tract
      cytologic diagnosis was retrospectively reviewed for 153 patients, and diagnostic
      accuracy was calculated. Cases were scored for the presence or absence of 32
      cytomorphologic criteria, and key features to distinguish high-grade TCC from
      benign lesions were assessed. There were two false-positive and four false
      negative diagnoses of TCC. Likelihood ratios for the diagnoses of benign,
      atypical, suspicious, and TCC were 0.2, 1.4, 3.9, and 32.8, respectively.
      Regression analysis showed that the cytologic features of aniso-nucleosis, high
      nuclear/cytoplasmic ratio, and nuclear overlapping were important in the
      separation of high-grade TCC from benign lesions. We conclude that by using these
      criteria, the accuracy of diagnosis of high-grade TCC could be improved.

PMID- 9237173
TI  - Contribution of flow cytometry to the diagnosis of gastric lymphomas in
      endoscopic biopsy specimens.
AB  - Gastric lymphomas seem to have unique clinical, pathologic, and immunophenotypic
      features that set them apart from nodal lymphomas. Microscopic examination of
      endoscopic biopsy specimens is the most frequent procedure used to diagnose
      gastric tumors, but it is very difficult, and sometimes impossible, to recognize
      lymphomas in endoscopic samples by histologic or even immunohistologic methods.
      Because most gastric lymphomas are of B-cell origin, we used flow cytometry to
      assess B-cell clonality in gastric biopsy specimens containing dense lymphocytic
      infiltrates thought to represent lymphoma. We prepared viable cell suspensions
      from unfixed specimens obtained from 29 consecutive patients who had a previous
      microscopic diagnosis of suspicious gastric lymphoid infiltrates. We performed
      immunophenotypic studies with multicolor flow cytometry, and we assessed
      clonality by examination of immunoglobulin (Ig) light-chain expression analyzed
      exclusively on B cells identified by anti-CD20 or CD19 antibodies. The mean
      number of cells recovered was 1.04 x 10(6), from an average of 5.5 gastric biopsy
      fragments per patient. In 26 of the 29 patients, the number of cells was adequate
      for analysis. We detected B-cell monoclonality in 16 cases, including 5 in which
      the percentage of clonal B cells was less than 5%. Of the 16 cases, only 8 could
      be diagnosed as lymphomas on morphologic grounds alone; the remaining 8 patients
      had either suspicious lymphoid infiltrates or chronic gastritis. The three cases
      with an insufficient number of cells were considered non-neoplastic either on
      histologic grounds alone or in conjunction with Southern analysis of Ig genes. We
      conclude that flow cytometric immunophenotypic analysis of freshly prepared cell
      suspensions obtained from endoscopic biopsy specimens can be used to evaluate
      gastric lymphocytic infiltrates. Specifically, the analysis of surface Ig light
      chain expression on B cells distinguishes between monoclonal (lymphoma) and
      polyclonal (nonlymphoma) infiltrates. The rapidity, ease, quantitative
      properties, and sensitivity of this technique make it a supplement to the
      morphologic assessment of gastric lymphoid infiltrates.

PMID- 9237175
TI  - Ovarian serous neoplasms of low malignant potential associated with focal areas
      of serous carcinoma.
AB  - This is a study of 12 cases of Stage III ovarian serous neoplasms of low
      malignant potential associated with focal areas (< 50%) of serous carcinoma. The
      purpose of this study was to assess the prognosis of serous tumors that had areas
      of serous carcinoma but were predominantly of low malignant potential. Eleven
      serous carcinomas were low grade, and one was high grade. All of the patients
      underwent surgical resection of the neoplasm and then chemotherapy. Eight
      patients died of disease after a follow-up of 17 to 94 months (mean, 52 mo).
      Three patients had no evidence of disease at 60, 69, and 75 months. One patient
      is alive with progressive disease at 58 months. Serous neoplasms of low malignant
      potential associated with focal areas (< 50%) of serous carcinoma are aggressive
      neoplasms that have a prognosis similar to that of serous carcinoma.

PMID- 9237176
TI  - HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the
      diagnosis of carcinoma.
AB  - The monoclonal antibody, HBME-1, generated against the microvillous surface of
      mesothelial cells, has been shown to have significant reactivity in histologic
      sections of follicular-derived thyroid malignancies. We examined the diagnostic
      utility of HBME-1 in thyroid fine-needle aspiration (FNA) specimens. Twenty-four
      aspirates from 23 patients were evaluated. Only cases with adequate cell blocks
      and tissue follow-up were studied. Immunocytochemical analysis was performed on
      air-dried, direct smears and on sections from Bouin's-fixed, paraffin-embedded
      cell blocks with a standard avidin-biotin peroxidase complex method with epitope
      retrieval. The same immunostaining technique was applied to the corresponding
      formalin-fixed tissue sections. Eight (57%) of the 14 malignant aspirates showed
      strong cytoplasmic and/or membrane immunoreactivity for HBME-1. The cell-block
      and direct-smear preparations were positive in five of seven papillary carcinomas
      (one follicular variant), one of one minimally invasive follicular carcinoma, and
      one of four hybrid tumors with mixed papillary and follicular features. An
      additional hybrid tumor case was focally positive only in the smear slide. The
      eighth positive case was an adenosquamous carcinoma of the larynx that invaded
      into the thyroid (smear preparation was negative for this case). The 10 benign
      lesions were negative. All of the malignant-tumor tissue sections were positive
      for HBME-1, and focal positivity was seen in 5 of 10 benign resection specimens.
      We conclude that a positive immunostain for HBME-1 on a thyroid FNA is supportive
      evidence that the lesion is a carcinoma, that a negative result for HBME-1 does
      not preclude the diagnosis of thyroid carcinoma, and that HBME-1 can be
      effectively applied to thyroid FNA specimens and can be a valuable adjunct in the
      cytologic diagnosis of thyroid malignancies.

PMID- 9237177
TI  - No role for human herpes virus 8 in the etiology of infantile capillary
      hemangioma.
AB  - Infantile capillary hemangiomas are vascular neoplasms that can appear quite
      infiltrative histologically and that are characterized by cords of cells with
      areas of marked cellularity. These lesions have been shown to contain a
      population of rapidly proliferative endothelial cells. Given the recent
      association between the presence of human herpes virus 8 (HHV8) and another
      proliferative vascular lesion, Kaposi's sarcoma, we used polymerase chain
      reaction technology to examine a series of 16 biopsy specimens from 15 infantile
      capillary hemangiomas for the presence of HHV8 DNA. We were unable to detect HHV8
      DNA in any of the lesions studied. All of the cases were examined in parallel
      with a case of Kaposi's sarcoma that was known to be positive for HHV8 DNA and a
      series of negative controls. In all of our cases, amplification of beta-globin
      gene DNA demonstrated adequate preservation of DNA in the tissue studied. These
      findings suggest that not all endothelial cell proliferations can be attributed
      to HHV8 and that the etiology of some of these conditions remains unclear.

PMID- 9237178
TI  - Molecular analysis of the IgH gene in 212 cases of Hodgkin's disease: correlation
      of IgH clonality with the histologic and the immunocytochemical features.
AB  - The aims of this study are to evaluate the frequency of clonal immunoglobulin
      heavy chain gene rearrangements in paraffin-embedded samples of Hodgkin's disease
      (HD) with use of the polymerase chain reaction method and to correlate the
      molecular findings with the histologic and immunocytochemical features. DNA
      extracts from paraffin-embedded sections from 212 HD samples were used for
      amplification of the IgH gene by use of framework 2 and framework 3 region
      primers. Immunohistochemical studies were performed on paraffin sections by use
      of monoclonal antibodies for CD20 and latent membrane protein-1 and polyclonal
      antibody for CD3. With use of both primer combinations, monoclonality was
      detected in 18.7% of lymphocyte-predominant HD cases and in 32.2% of classical HD
      cases. These results suggest that immunoglobulin heavy chain gene clonal
      rearrangements are relatively frequent in classical HD. In addition, the
      statistical analyses of the genotypic and immunocytochemical data revealed that
      the detection of B-cell populations is significantly associated with the
      expression of CD20 on HRS cells. There was, however, no correlation between the
      histologic subtype, the percentage of HRS cells, the presence of latent membrane
      protein-1 expression, and the molecular analysis results.

PMID- 9237179
TI  - Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation
      of liver tumors.
AB  - A monoclonal antibody highly specific for benign and malignant hepatocytes
      (HepPar 1) was evaluated as part of an antibody panel used to differentiate
      hepatocellular from nonhepatocellular neoplasms. Sixty-five liver tumors and two
      extrahepatic tumors from patients with documented liver tumors were studied.
      Twenty-two neoplasms were of hepatocellular origin, three were combined
      hepatocellular/cholangiocarcinomas, and the remainder were of nonhepatocellular
      origin. HepPar 1 alone had an 82% sensitivity and 90% specificity for the
      detection of hepatocellular neoplasms. The corresponding values for alpha
      fetoprotein were 57% and 97%. Polyclonal antibody to carcinoembryonic antigen
      (canalicular pattern) had a sensitivity of 79% and specificity of 97% for these
      tumors. The use of antibody panels provided superior results when compared with
      individual antibodies. In summary, HepPar 1 monoclonal antibody is a useful
      reagent for the differential diagnosis of hepatocellular tumors. Its utility is
      enhanced when it is used as part of a diagnostic antibody panel.

PMID- 9237180
TI  - Immunohistochemistry of unclassified sex cord-stromal tumors of the testis with a
      predominance of spindle cells.
AB  - Unclassified sex cord-stromal tumors (SCSTs) of the testis comprised
      predominantly of spindle cells can be difficult to classify. To achieve better
      definition of these tumors, we examined the histologic, histochemical, and
      ultrastructural features of four unclassified SCSTs with spindle-cell features,
      and compared their immunohistochemical features with those of 24 other SCSTs of
      the testis and ovary. Three of the spindle-cell tumors were composed of
      relatively short spindled cells with prominent nuclear grooves and intermixed
      epithelioid cells. All of the three were located adjacent to the rete testis. The
      fourth case consisted of elongate spindle cells that were reminiscent of smooth
      muscle. In all of the four cases, reticulin enveloped aggregates of cells of
      various sizes but not individual cells. Ultrastructural analysis of two of the
      spindle-cell tumors revealed desmosomes, numerous thin filaments, and focal dense
      bodies. Immunohistochemically, all of the four tumors were reactive for S-100
      protein and smooth muscle actin. Staining for S-100 protein and smooth muscle
      actin was also observed in three of six granulosa cell tumors and both juvenile
      granulosa cell tumors. Although variable staining for S-100 protein was found in
      5 of the 12 other SCSTs (4 Leydig cell, 6 Sertoli-Leydig cell, and 2
      unclassifiable ovarian SCSTs), reactivity for smooth muscle actin was present in
      only 1 Sertoli-Leydig cell tumor. In contrast, all of the four ovarian
      fibromas/thecomas were reactive for smooth muscle actin but failed to stain for S
      100 protein. Taken together, the histologic, histochemical, immunohistochemical,
      and ultrastructural features of the spindle-cell tumors are similar to those of
      granulosa cell tumors. Reactivity for S-100 protein and smooth muscle actin is
      characteristic of these tumors. These tumors should be distinguished from other
      unclassified SCSTs.

PMID- 9237181
TI  - Donor or recipient origin of post-transplantation lymphoproliferative disorders:
      evaluation by in situ hybridization.
AB  - Post-transplantation lymphoproliferative disorders (PTLDs) have been reported
      after bone marrow and solid-organ transplantation. It might be of interest to
      know the origin of PTLDs, because it has been suggested that a donor origin could
      be related to a better prognosis. We studied five cases of PTLD in sex-mismatched
      allografted recipients by in situ hybridization technique for chromosome Y on
      isolated cells as well as on frozen and on routinely fixed and paraffin-embedded
      material. Two proved to be of donor origin, including the only case of PTLD
      arising in the graft, and three of recipient origin. The best results were
      obtained on isolated cells, but it must be emphasized that hybridization on
      tissue sections from frozen material or from material fixed in formalin or in
      formalin-acetic acid-alcohol and then paraffin embedded also gave good results.
      Hybridization after fixation in Bouin's liquid was not reliable. These results
      suggest that evaluation of the origin of PTLDs can easily be performed on
      routinely processed cytologic and histologic material.

PMID- 9237182
TI  - Key features distinguishing post-transplantation lymphoproliferative disorders
      and acute liver rejection.
AB  - Post-transplantation lymphoproliferative disorder (PTLD) and acute rejection are
      two serious complications of orthotopic liver transplantation that can have a
      similar histologic appearance. We undertook the present study to assess the best
      way to distinguish these two entities. We studied histologic features,
      immunophenotyping, and Epstein-Barr virus (EBV) status, as assessed by
      immunohistochemical stain and in situ hybridization (ISH), in three groups: Group
      I, 8 cases of PTLD post-orthotopic liver transplantation with liver involvement;
      Group II, 15 cases diagnosed with acute liver rejection (control group); and
      Group III, a subset of 6 biopsy specimens from 4 patients of Group I whose graft
      rejection was diagnosed within the 2 months preceding the diagnosis of PTLD. The
      mean proportion of plasma to plasmacytoid cells in most cases from Group I was
      more than 40%, whereas from Group II it was less than 25% (P = .0001). There was
      a higher number of B lymphocytes than T lymphocytes in Group I. The numbers of
      mitotic figures and immunoblasts were significantly different in the two groups
      (P < .0001 and P = .0005, respectively), being higher in the patients with PTLD.
      EBV immunostain was most specific for the diagnosis of PTLD (75% positive in
      Group I, negative in Group II). ISH for EBV-encoded RNA was positive in 87% of
      cases in Group I and only 6.6% of cases in Group II (P = .0005). In Group III,
      four of the six liver biopsy specimens had a low plasma cell count and were
      negative for EBV studies. The other two biopsy specimens in this group had 70 to
      80% plasma cell infiltrate, in addition to positive EBV immunostain and ISH in
      one, for which tissue was available for study. We conclude that viral studies and
      assessment of the number of plasma cells and B lymphocytes can help to
      distinguish between acute rejection and early PTLD.

PMID- 9237183
TI  - Anti-MOC-31: a potential addition to the pulmonary adenocarcinoma versus
      mesothelioma immunohistochemistry panel.
AB  - MOC-31 expression has recently been advocated as an immunohistochemical marker
      for distinguishing mesothelioma from adenocarcinoma in tissue sections. We
      studied formalin-fixed, paraffin-embedded tissue from 23 pleural mesotheliomas
      and 23 primary pulmonary adenocarcinomas for immunoreactivity with anti-MOC-31, a
      human epithelial-related antigen. All of the 23 adenocarcinomas strongly
      expressed the marker, whereas only one of the mesotheliomas showed weak
      reactivity. These results demonstrate the usefulness of anti-MOC-31 in
      differentiating pulmonary adenocarcinoma from mesothelioma.

PMID- 9237184
TI  - Quantitation of HER-2/neu and c-myc gene amplification in breast carcinoma using
      fluorescence in situ hybridization.
AB  - HER-2/neu and c-myc amplification or overexpression have been reported to be
      associated with poor prognosis in breast carcinoma. The prognostic significance,
      however, remains somewhat controversial, partly because of discrepancies among
      different methodologies used for detection of the oncogene amplification or
      overexpression. Fluorescence in situ hybridization (FISH) has recently been shown
      to be a useful technique for analyzing genetic alterations in interphase nuclei
      in various tumors. In this study, FISH was used to quantitate HER-2/ neu and c
      myc gene amplification in touch preparations of frozen tissue from 100 node
      negative breast carcinomas. HER-2/neu amplification was found to be associated
      with an abnormal DNA index (P < .001) and tumor size (P < .04). Amplification of
      c-myc was associated with S phase (P < .0003), abnormal DNA index (P < .003), and
      a negative estrogen receptor status (P < .01). The coamplification of both
      oncogenes was strongly associated with an abnormal DNA index (P < .0001) and with
      tumor size (P < .009). The use of FISH for detection of HER-2/neu gene
      amplification was 92% concordant with immunocytochemistry (ICC) used for
      detection of overexpression of HER-2/neu protein. Fifteen of the 100 cases were
      both amplified for HER-2/neu by FISH and positive by ICC analysis. Seven cases
      without HER-2/neu gene amplification demonstrated HER-2/neu protein
      overexpression by ICC. One HER-2/neu-amplified case was negative by ICC. Repeat
      analysis of a subset of cases showed FISH to be a more reproducible method than
      ICC in the analysis of HER-2/neu in touch preparations of breast carcinoma. FISH
      is a rapid and reproducible method that allows the accurate measurement of the
      level of oncogene amplification within interphase nuclei. The use of FISH should
      provide a more accurate assessment of the prognostic significance of oncogene
      amplification in breast carcinoma.

PMID- 9237186
TI  - Primary amyloid tumor of the breast: a case report and review of the literature.
AB  - We present a case of primary amyloid tumor of the breast. Although isolated
      amyloidosis of other organs occurs frequently, it is extremely rare in the
      breast: only seven well-documented cases have been reported. Our case has the
      additional unusual feature of belonging to the amyloid AA type of amyloid instead
      of the more common amyloid AL type. Immunohistochemical studies are documented.
      The clinical and pathologic characteristics of all of the reported cases are
      tabulated. These cases suggest that primary amyloid tumor in the breast has the
      following clinicopathologic features: it affects postmenopausal women between the
      ages of 54 to 82 years (mean, 68 yr), involves the right breast more often than
      the left (ratio, 3:1), is clinically frequently misdiagnosed as carcinoma, and
      probably has a diverse pathogenesis.

PMID- 9237185
TI  - bcl-2 and p53 in endometrial adenocarcinoma.
AB  - bcl-2 protein is expressed in normal endometrium and seems to be under hormonal
      control. Its role in endometrial carcinoma (EC) is largely unknown. EC can serve
      as a good model to investigate the role of bcl-2 in hormone-dependent neoplasia,
      because EC shows a spectrum of hormonally induced changes in which bcl-2 might
      have a potential role. p53, a tumor suppressor gene, is the most commonly mutated
      gene in human cancer and is a frequent abnormality in advanced EC. There is
      interaction between p53 and bcl-2 proteins in the regulation of physiological
      programmed cell death and in malignant processes. In this study, we performed
      immunohistochemical investigations of the expression of bcl-2 and p53 in 57 ECs,
      along with estrogen and progesterone receptors (ERs, PRs), to correlate the
      expression patterns of bcl-2 and p53 in different grades of EC with relation to
      clinicopathologic parameters. The average age of the patients was 61 years. Among
      57 ECs, there were 13 noninvasive ECs and 44 ECs with various depths of invasion.
      p53 was positive in 21 of 57 cases, and bcl-2 was positive in 42 of 57. ER and PR
      were positive in 24 of 57 cases; PR and ER alone were positive in 15 and 2 cases,
      respectively. bcl-2 expression is present in ECs, and its expression is related
      to grade and stage. bcl-2 expression is strongly associated with PR, whereas p53
      is associated with higher grade and is inversely related to PR positivity.

PMID- 9237187
TI  - Guidelines of the Papanicolaou Society of Cytopathology for fine-needle
      aspiration procedure and reporting. The Papanicolaou Society of Cytopathology
      Task Force on Standards of Practice.
AB  - As medical care moves toward outpatient and managed care, FNA becomes an
      indispensable biopsy procedure that can replace many surgical biopsies. The
      reliability of the procedure is maximized by rapid assessment of the aspirates
      and the team approach (the cytopathologist, radiologist, and clinician working
      closely together). Proper training and maintenance of competency are central to
      success. QA and QI programs are excellent means to monitor competency and improve
      performance. Aspirators who persistently produce a high rate of unsatisfactory
      aspirates (> 15%) should be identified and given remedial training. Clear,
      precise communication and rapid turn-around time for reporting are critical.

PMID- 9237189
TI  - A single-bead decode strategy using electrospray ionization mass spectrometry and
      a new photolabile linker: 3-amino-3-(2-nitrophenyl)propionic acid.
AB  - A new linker that employs a photosensitive 3-amino-3-(2-nitrophenyl)propionyl
      functionality (ANP-resin) has been developed for the preparation of C-terminal
      carboxamides. A wide range of carboxamides were prepared and identified using the
      ANP-resin and electrospray ionization mass spectrometry. A single bead containing
      tripeptide Fmoc-Asp-Arg(Tos)-Val-NH2 was isolated, photocleaved and the peptide
      was characterized by tandem mass spectrometry, thereby verifying a library decode
      strategy that avoids complex tagging procedures.

PMID- 9237190
TI  - Multiple simultaneous synthesis of phenolic libraries.
AB  - A series of analogous arrays of small, non-peptidyl, non-oligomeric compounds
      were synthesized on polystyrene resin. With the aid of a functionally
      differentiated phenolic scaffold, the batch preparation of unique benzamide and
      urea resins was accomplished, which were further derivatized in modified 96-well
      plates. An efficient cleavage reaction of the phenyl benzoate link enabled the
      isolation of more than 600 phenolic compounds in milligram quantities that were
      suitable for direct biological screening. The technology described herein
      represents a facile, economical approach to non-peptidyl chemical diversity.

PMID- 9237191
TI  - Mapping the detailed specificity of a calcium-dependent monoclonal antibody
      through the use of soluble positional scanning combinatorial libraries:
      identification of potent calcium-independent antigens.
AB  - The detailed specificity of monoclonal antibody M1, which has been reported to
      bind in a calcium-dependent manner to the 'FLAG' sequence DYKDDDDK-NH2, was
      examined using soluble hexa- and decapeptide positional scanning synthetic
      combinatorial libraries (PS-SCLs) made up of 52 x 10(6) and 4 x 10(12) different
      sequences, respectively. To study the influence of calcium on the specificity of
      this antigen-antibody interaction, each PS-SCL was screened in the presence and
      absence of calcium using a competitive ELISA. Overall, peptide mixtures had
      greater inhibitory activity against mAb M1 binding to FLAG in the absence of
      calcium. A total of 16 individual hexapeptides were identified, all of which
      contained the motif-DYK_K_(-), and were recognized by mAb M1 in the absence of
      calcium with 50- to 100-fold higher affinity than the FLAG octapeptide (IC50 =
      273 nM). On average, the same set of peptides bound 10-fold less effectively in
      the presence of calcium. Upon screening the decapeptide PS-SCL in the absence of
      calcium, lysine was also more active in the fifth position than the original
      aspartic acid. Based on the screening results, 24 individual decapeptides were
      prepared and were found to have activities 10- to 100-fold higher than the FLAG
      octapeptide in the absence of calcium. The specificity of lysine at the fifth
      position in the antigen-antibody interaction was further examined by synthesizing
      and assaying substitution analogs at this position for the octapeptide and
      hexapeptide forms of the FLAG sequence, as well as for two hexapeptides
      identified from the PS-SCL. Truncation analog analysis was also carried out on
      the FLAG octapeptide to determine optimal antigen length for antibody binding.
      Overall, lysine at the fifth position could be substituted with ornithine with no
      significant loss in activity, and peptide length was not a critical factor for
      antibody binding in the absence of calcium. Also, the octapeptide having lysine
      at the fifth position in place of the aspartic acid had the same activity in the
      presence or absence of calcium. This study demonstrates the ease and
      effectiveness of PS-SCLs over individual peptide analogs for the examination of
      the degree of cross-reactivity for a given monoclonal antibody as well as for the
      identification of novel, high-affinity peptides.

PMID- 9237192
TI  - Libraries of random-sequence polypeptides produced with high yield as carboxy
      terminal fusions with ubiquitin.
AB  - Libraries of random-sequence polypeptides have been shown to be valuable sources
      of novel molecules possessing a variety of useful biologic-like activities, some
      of which may hold promise as potential vaccines and therapeutics. Previous random
      peptide expression systems were limited to low levels of peptide production and
      often to short sequences. Here we describe a series of libraries designed for
      increased polypeptide length. Cloned as carboxy-terminal extensions of ubiquitin,
      the fusions were produced in E. coli at high levels, and were purified to
      homogeneity. The majority of the extension proteins examined could be cleaved
      from ubiquitin by treatment with a ubiquitin-fusion hydrolase. The libraries
      described here are appropriate sources of novel polypeptides with desired binding
      or catalytic function, as well as tools with which to examine inherent properties
      of proteins as a whole. Toward the latter goal, we have examined structural
      properties of random-sequence proteins purified from these libraries. Quite
      surprisingly, fluorescence emission spectra of intrinsic tryptophan residues in
      several purified fusion proteins, under native-like and denaturing conditions,
      often resemble those expected for folded and unfolded states, respectively. The
      results presented here detail an important expansion in the range of potential
      uses for random-sequence polypeptide libraries.

PMID- 9237194
TI  - Adaptive walks with noisy fitness measurements.
AB  - Adaptive walks constitute an optimization technique for searching a space of
      possible solutions, for example, a space of different molecules. The goal is to
      find a point in space (a molecule) that is optimal or near-optimal in some
      property, generally referred to as the 'fitness', such as its ability to bind to
      a given receptor. Adaptive walking, an analog of natural selection, is a powerful
      technique for searching landscapes. However, errors in the measurements will
      cause errors in the adaptive walks. Mutant molecules of higher fitness may be
      ignored or mutants of lower fitness may be accepted. To examine the effect of
      measurement error on adaptive walks, we simulate single-agent hill-climbing walks
      on NK landscapes of varying ruggedness where Gaussian noise is added to the
      fitness values to model measurement error. We consider both constant measurement
      noise and noise whose variance decays exponentially with fitness. We show that
      fitness-independent noise can cause walks to 'melt' off the peaks in a landscape,
      wandering in larger regions as the noise increases. However, we also show that a
      small amount of noise actually helps the walk perform better than with no noise.
      For walks in which noise decreases exponentially with fitness, the most
      characteristic behavior is that the walk meanders throughout the landscape until
      it stumbles across a point of relatively high fitness, then it climbs the
      landscape towards the nearest peak. Finally, we characterize the balance between
      selection pressure and noise and show that there are several classes of walk
      dynamic behavior.

PMID- 9237193
TI  - A combinatorial method for constructing libraries of long peptides displayed by
      filamentous phage.
AB  - We describe the construction and screening of a random peptide library displayed
      by filamentous phage. The peptides are expressed in multiple copies on the
      filamentous phage M13 as amino-terminal fusions with the major coat protein, the
      product of gene VIII. These libraries are efficiently screened for reactive
      peptides, using a combination of panning in solution followed by a plaque lift
      assay. Advantages of this system are that both high- and low-affinity phage
      clones are simultaneously identified and the analysis of non-reactive phage is
      minimized. The vector system utilized to construct this library enables it to be
      used for the construction of peptide libraries employing a combinatorial cloning
      strategy. This feature makes it especially suitable for construction of peptide
      libraries using codon-based oligonucleotide synthesis. The vectors also allow
      rapid optimization and modification of lead peptides by codon-based mutagenesis.
      A 20-amino acid long random peptide library of 1 x 10(9) members was constructed
      and screened for peptides that bound to (i) a monoclonal antibody recognizing the
      amino-terminus of beta-endorphin; (ii) a monoclonal antibody recognizing a
      peptide epitope derived from the v-ros oncogene product; and (iii) the constant
      region of murine IgG2b. The approach described here provides a means for the
      construction of customized libraries that can be screened with a variety of
      target molecules.

PMID- 9237195
TI  - In vitro selection methodologies to probe RNA function and structure.
AB  - In vitro selection, or SELEX, has been used both to characterize the interaction
      of natural nucleic acids with proteins and to generate novel nucleic acid-binding
      species, or aptamers. Although numerous reports have demonstrated the power of
      the technique, they have not expanded on the methodologies that can be used for
      selection. This review focuses on the considerations and problems involved in
      selecting protein-binding aptamers from a random-sequence RNA pool. As an
      illustration, we describe two approaches to selecting aptamers to a particular
      target, the HTLV-I Rex protein. In the first, complete randomization is used to
      find an artificial, high-affinity RNA binding site. In the second, the
      contributions of individual nucleotides and/or base pairs to the natural Rex
      binding element are determined by mutating the wild-type sequence and selecting
      active binding variants.

PMID- 9237196
TI  - Utilization of multiple phage display libraries for the identification of
      dissimilar peptide motifs that bind to a B7-1 monoclonal antibody.
AB  - Seven random peptide libraries (two displaying linear peptides and five
      displaying cysteine-constrained peptides) were constructed as gene III fusion
      proteins of the bacteriophage fd-tet. These libraries were used to screen a
      blocking monoclonal antibody raised against B7-1 (CD80), a human cell surface
      antigen that binds two T cell receptors, CD28 and CTLA-4. After three rounds of
      screening against the immobilized antibody, 1000-fold enrichment was observed in
      libraries displaying both linear and cysteine-constrained peptides. DNA
      sequencing of the enriched phage revealed two distinct consensus sequences:
      HXG(A/Y)XH and DVCXXGGPGC. Phage expressing these consensus sequences bound to
      L307.4 but not to an isotype matched antibody, indicating that binding was
      antibody specific. Synthetic peptides corresponding to both motifs inhibited
      phage binding to L307.4, indicating that the gene III protein is not required for
      peptide binding. In addition, the cyclized forms of synthetic peptides containing
      the DVCXXGGPGC motif were capable of inhibiting L307.4 binding to soluble B7-1/Fc
      fusion. Moreover, phage expressing only the HXG(A/Y)XH consensus sequence were
      inhibited from binding to L307.4 by the presence of chelating agents. These
      results indicate that the framework within which the peptide is presented on the
      surface of the phage may allow the identification of unique peptide motifs with
      distinct binding characteristics. These peptide motifs could be used for the
      design of peptidomimetics with therapeutic applications if they inhibit the
      binding of B7-1 to its T cell receptors.

PMID- 9237197
TI  - Structural aspects of antibody-antigen interaction revealed through small random
      peptide libraries.
AB  - Two small random peptide libraries, one composed of 4550 dodecapeptides and one
      of 8000 tripeptides, were synthesized in newly developed credit-card format
      miniPEPSCAN cards (miniPEPSCAN libraries). Each peptide was synthesized in a
      discrete well (455 peptides/card). The two miniPEPSCAN libraries were screened
      with three different monoclonal antibodies (Mabs). Two other random peptide
      libraries, expressed on the wall of bacteria (recombinant libraries) and composed
      of 10(7) hexa- and octapeptides, were screened with the same three Mabs. The aim
      of this study was to compare the amino acid sequence of peptides selected from
      small and large pools of random peptides and, in this way, investigate the
      potential of small random peptide libraries. The screening of the two miniPEPSCAN
      libraries resulted in the identification of a surprisingly large number of
      antibody-binding peptides, while the screening of the large recombinant
      libraries, using the same Mabs, resulted in the identification of only a small
      number of peptides. The large number of peptides derived from the small random
      peptide libraries allowed the determination of consensus sequences. These
      consensus sequences could be related to small linear and nonlinear parts of the
      respective epitopes. The small number of peptides derived from the large random
      peptide libraries could only be related to linear epitopes that were previously
      mapped using small libraries of overlapping peptides covering the antigenic
      protein. Thus, with respect to the cost and speed of identifying peptides that
      resemble linear and nonlinear parts of epitopes, small diversity libraries based
      on synthetic peptides appear to be superior to large diversity libraries based on
      expression systems.

PMID- 9237198
TI  - Directed evolution studies with combinatorial libraries of T4 lysozyme mutants.
AB  - Gene duplication with divergence to new functions has been an important mechanism
      in protein evolution. However, the questions of how many new functions can arise
      from a particular ancestral gene and how many mutational steps are typically
      required to generate new functions have been difficult to approach
      experimentally. We have addressed these questions using T4 lysozyme as a model
      system by synthesizing two combinatorial libraries of > 10(7) mutant T4 lysozyme
      genes: one library with an average of 14 missense mutations spread throughout the
      gene and one library in which 13 active site residues have been simultaneously
      randomized. These libraries were placed under selection in lacZ or pheA deficient
      strains of E. coli to investigate whether they sample sufficient diversity to
      contain mutants with acquired beta-galactosidase or prephenate dehydratase
      activities. Although neither selection yielded T4 lysozyme mutants with these new
      activities, a novel E. coli locus was cloned that weakly complements these
      mutants, allowing them to form 1 mm colonies in 4-6 weeks. This growth rate
      corresponds to a turnover number of approximately 1000 or 25 min-1 for the lacZ
      or pheA complementation systems, respectively, thus defining the limits of
      evolved enzymatic activity detectable in these selections. Thus, the strong
      selective pressure uncovered an unexpected solution to the biochemical blocks, a
      frequently observed phenomenon in selection experiments. The characterization of
      this locus will allow its elimination from future E. coli complementation
      schemes.

PMID- 9237200
TI  - Combinatorial synthesis of small-molecule libraries using 3-amino-5
      hydroxybenzoic acid.
AB  - A non-peptide library of 2001 compounds has been prepared utilizing solid-phase
      techniques. The split/combine method was demonstrated to work well to form
      mixtures of compounds based on 3-amino-5-hydroxybenzoic acid as a core structure.
      The benzoic acid of the core structure served as the attachment point for the
      resin and the amino and hydroxy positions were variably substituted.

PMID- 9237199
TI  - A new combination of protecting groups and links for encoded synthetic libraries
      suited for consecutive tests on the solid phase and in solution.
AB  - A strategy for high-throughput evaluation of combinatorial compound libraries is
      reported, which circumvents the necessity to test complex mixtures. The method is
      based on a new combination of protecting groups, solid-phase linker and tags. The
      bulk of the library first undergoes a binding assay with the components grafted
      on beads. A selection of beads carrying strong ligands is stripped from the
      labelled target and distributed into microvessels. The ligands are cleaved and
      rinsed into microeluates. Subsequently, a more detailed characterization with a
      functional assay in solution determines the best performers, which are identified
      through the peptidic tag left behind on the corresponding mother bead.

PMID- 9237201
TI  - Antibiotic activity of polyketide products derived from combinatorial
      biosynthesis: implications for directed evolution.
AB  - A library of over 100 polyketides, generated via combinatorial cloning of genes
      encoding subunits of aromatic polyketide synthases, was screened for molecules
      capable of inhibiting the growth of gram-positive bacteria. A total of 26
      polyketides, with varying levels of antibiotic activity in filter-disk assays,
      were purified. Most bioactive polyketides were produced as relatively minor
      compounds (< 1 mg/l), although two major anthraquinones, with yields in the range
      of 10-100 mg/l, were also identified and structurally characterized. When tested
      against Bacillus subtilis 168 beta, they were found to cause a 50% reduction in
      colony-forming units at concentrations of 20 and 300 micrograms/ml, respectively.
      We speculate that many of the minor (and possibly more potent) bioactive
      polyketides are synthesized via nonspecific enzymatic modifications of shunt
      products derived from engineered polyketide synthase pathways. If so, then these
      'fortuitous' pathways should be amenable to further rationally guided
      manipulation. Our results support the notion that combinatorial biosynthesis can
      be used to generate novel, biologically active molecules. They also point to the
      feasibility of designing mutagenesis selection experiments aimed at the directed
      evolution of organic molecules with desirable pharmaceutical properties.

PMID- 9237202
TI  - Solid phase organic synthesis (SPOS): a novel route to diketopiperazines and
      diketomorpholines.
AB  - The solid phase synthesis of libraries containing a 1,3,4,6-tetrasubstituted-2,5
      diketo-1,4-piperazine scaffold (DKP) or a 3,4,6-trisubstituted-2,5-diketo-1,4
      morpholine scaffold (DKM) from alpha-bromocarboxylic acids and amines is
      described. Using a design strategy which we refer to as divergent library design,
      both templates were prepared from a common intermediate. The general utility of
      this synthetic route in creating novel, non-peptidyl chemical libraries is
      discussed.

PMID- 9237203
TI  - Evolutionary molecular engineering in Japan.

PMID- 9237204
TI  - High-throughput screening strategies to identify inhibitors of protein-protein
      interactions.

PMID- 9237206
TI  - Structurally homogeneous and heterogeneous synthetic combinatorial libraries.
AB  - We have designed and synthesized structurally homogeneous and heterogeneous
      nonpeptide libraries. Structurally homogeneous libraries are characterized by the
      presence of one common structural unit, a scaffold, in all library compounds
      (e.g. cyclopentane, cyclohexane, diketopiperazine, thiazolidine). In structurally
      heterogeneous libraries different organic reactions (acylation, etherification,
      reductive amination, nucleophilic displacement) were applied to connect
      bifunctional building blocks unrelated in structure (aromatic hydroxy acids,
      aromatic hydroxy aldehydes, amino alcohols, diamines, and amino acids). The focus
      of this communication is to document the use of bifunctional building blocks for
      the design and synthesis of structurally heterogeneous libraries of N-(alkoxy
      acyl)amino acids, N,N'-bis-(alkoxy acyl)diamino acids, N-acylamino ethers, N
      (alkoxy acyl)amino alcohols, N-alkylamino ethers, and N-(alkoxy aryl)diamines.

PMID- 9237205
TI  - Mapping protein-protein contact sites using cellulose-bound peptide scans.
AB  - We have characterized the interaction of two monoclonal antibodies with their
      respective antigens using cellulose-bound sets of overlapping peptides (peptide
      scans). Both antibodies CB/RS/5 and CB/MT/1 recognize discontinuous epitopes
      present in human interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF
      alpha). In addition, the interaction between TNF-alpha and its 55-kDa receptor
      (TNF-R) was investigated by the same approach. Both antibodies, as well as TNF
      alpha, interacted with two or more regions of the peptide scans. Antibody-binding
      competition studies between the native antigens and peptides, covering single
      parts of the binding regions, enabled us to distinguish between binding to the
      paratope or other regions of the antibody. The combination of these experimental
      approaches allowed the identification of short antigen-derived sequences that are
      separated on the primary sequence but close in space on the surface of IL-10 and
      TNF-alpha, thus representing putative discontinuous epitopes. In the case of the
      TNF-R-derived peptide scans, two of the identified regions interact with the
      structurally similar TNF-beta in the TNF-beta-TNF-R complex. These data indicate
      that this approach should be generally applicable for mapping nonlinear protein
      protein contact sites.

PMID- 9237207
TI  - Construction and screening of M13 phage libraries displaying long random
      peptides.
AB  - We have constructed two phage display libraries expressing N-terminal pIII
      fusions in M13 composed of 37 and 43 random amino acid domains, respectively. The
      D38 library expresses 37 random amino acids with a central alanine residue, and
      the DC43 library contains 43 random amino acids with a central cysteine flanked
      by two glycine residues, giving the displayed peptide the potential to form
      disulfide loops of various sizes. We demonstrate that the majority of random
      sequences in both libraries are compatible in pentavalent display with phage
      viability. The M13 phage display vector itself has been engineered to contain a
      factor Xa protease cleavage site to provide an alternative to acid elution during
      affinity selection. An in-frame amber mutation has been inserted between the pIII
      cloning sites to allow for efficient selection against nonrecombinant phage in
      the library. These libraries have been panned against mAb 7E11-C5, which
      recognizes the prostate-specific membrane antigen (PSM). Isolated phage display a
      consensus sequence that is homologous to a region in the PSM molecule.

PMID- 9237209
TI  - The impact of polystyrene resins in solid-phase organic synthesis.
AB  - A major objective of the DIVERSOMER technology is to provide pure and
      characterized compounds for biological testing in order to prevent 'false
      negatives' in our libraries. On several occasions, analysis of the final products
      by 1H-NMR and MS, has revealed by-products from the polystyrene solid support.
      Subsequently, three alternative methods were studied to remove polystyrene by
      products; (i) prewashing of the resin prior to execution of the synthesis; (ii)
      pretreatment of the resin with the cleavage conditions consistent with the solid
      phase synthesis reaction scheme; and (iii) parallel purification.

PMID- 9237208
TI  - Bifunctional scaffolds as templates for synthetic combinatorial libraries.
AB  - A small-molecule synthetic combinatorial library was designed and synthesized
      that features potential pharmacophores attached to a variety of small cyclic
      scaffolds. The synthesis of the library involved randomization of three types of
      building blocks: 20 amino acids, 10 aromatic hydroxy acids and 21 alcohols,
      totaling a library complexity of 4200 compounds. Mitsunobu polymer-supported
      etherification was used in the last randomization. The library compounds were
      attached to beads via an ester-bond linkage enabling both on-bead as well as in
      solution screening. When the library was tested against a model target,
      streptavidin, specific binders were found. The structures of the most active
      compounds were determined from the fragmentation pattern in MS/MS experiments.

PMID- 9237210
TI  - Hamming chromatography.
AB  - Selection of molecules with desired properties from random pools of biopolymers
      has become a powerful tool in biotechnology. On designing an evolution
      experiment, a certain knowledge of the concomitant fitness landscape is clearly
      helpful to set up the optimal experimental conditions. The correlation function
      is a useful means of characterizing a given landscape, since it can be
      efficiently measured if one has a method of separating a pool of random sequences
      according to their Hamming distance from a moderately small number of test
      sequences. In this paper we describe a special type of hybridization
      chromatography, where a mixture of oligomers (partially) complementary to a given
      test sequence is hybridized to the test sequence, covalently bound to a matrix.
      DNA oligomers are eluted in an 'effective temperature gradient' using conditions
      that minimize the differences of effects of GC versus AT pairs on the melting
      temperatures. This method should be a means to quickly separate error classes and
      thus be the crucial step in characterizing fitness landscapes of biopolymers
      through an experimental approach. It would also be a useful tool to design
      sequence pools with a bias towards desired mutant spectra.

PMID- 9237212
TI  - Assessing the ability of chemical similarity measures to discriminate between
      active and inactive compounds.
AB  - A method for assessing the biological discriminating power of chemical similarity
      measures is presented. The main concern of this work was to develop an objective
      way of evaluating different similarity measures in terms of how well they
      distinguished between active and inactive compounds. In addition, we have
      explored the level of similarity required for optimal separation and commented on
      its implications for work in the field of chemical diversity studies. The results
      for one simple similarity measure showed that statistically significant
      separation could be achieved, and indicated a reasonable similarity value for
      future work.

PMID- 9237211
TI  - Synthetic library techniques: subjective (biased and generic) thoughts and views.
AB  - Various aspects of synthetic diversity generation and screening are discussed.
      Controversial issues are raised and different points of view are presented. We
      hope the article will stimulate thinking about the utilization of library
      techniques and start a discussion about questions concerning their application.

PMID- 9237213
TI  - Structure and properties of TentaGel resin beads: implications for combinatorial
      library chemistry.
AB  - In view of the widespread use of TentaGel resin beads for the synthesis of
      combinatorial libraries, the properties of TentaGel resin have been examined
      using a combination of confocal laser microscopy and NMR spectroscopy. Evidence
      is presented that trypsin, a 23.5-kDa enzyme, can penetrate to the core of 90
      microns TentaGel beads, and that the matrix of such beads permits molecular
      motion at a similar rate to that in solution. The beads act as a separate gel
      phase rather than as a porous solid. These conclusions have important
      implications for the bioassay of on-bead combinatorial chemical libraries.

PMID- 9237214
TI  - Novel alpha-glucosidase inhibitors identified using multiple cyclic peptide
      combinatorial libraries.
AB  - Twenty-six cyclic synthetic peptide combinatorial libraries (disulfides and
      lactams) of varying size and composition, representing 6.8 x 10(3) to 4.7 x 10(7)
      individual peptides, were synthesized along with their respective linear analogs.
      One of the hexapeptide lactam libraries (cyclo[xXxXxN]) was found to have
      significant alpha-glucosidase inhibitory activity. This library was carried
      through an iterative process of synthesis and screening, during which all of the
      five mixture positions (x and X) were successively defined. As the result of this
      process, potent and selective alpha-glucosidase inhibitors were identified.

PMID- 9237215
TI  - Analysis of novel streptavidin-binding peptides, identified using a phage display
      library, shows that amino acids external to a perfectly conserved consensus
      sequence and to the presented peptides contribute to binding.
AB  - Streptavidin-binding peptides containing the consensus amino acid sequence motif
      EPDW were identified using a phage display library. Phage presenting peptides
      containing these sequences bound streptavidin in a biotin-sensitive fashion and
      could be eluted with biotin. The previously identified 'streptag' peptide
      sequence (AWRHPQGG) competed with phage presenting the EPDW consensus sequence
      for streptavidin binding. Furthermore, the EPDW sequence has two amino acids in
      common with yet another previously identified streptavidin-binding sequence,
      GDWVFI, which has similar biochemical properties. Binding inhibition studies
      revealed that residues flanking EPDW, as well as residues of the modified phage
      pIII product to which displayed peptides are fused, contributed to streptavidin
      binding. The derivation of small molecules based on the structure of peptides
      selected using display methods is a potentially important application of phage
      display technology. The relevance of the observations made here for that
      application are discussed. Finally, a group of 'nuisance' peptides of the
      consensus sequence WHWWXW, whose binding specificity has not been fully
      elucidated, but which have been isolated in a number of biopanning experiments,
      including those that do not utilize streptavidin, are also described.

PMID- 9237216
TI  - Quantitation of combinatorial libraries of small organic molecules by normal
      phase HPLC with evaporative light-scattering detection.
AB  - The advantages of evaporative light-scattering detection over UV detection for
      the quantitation of combinatorial libraries composed of small organic compounds
      by HPLC are described. The detector's response is independent of the sample
      chromophore, which makes it well-suited to chromatographic analyses of mixtures
      of dissimilar solutes. Thus, HPLC with evaporative light-scattering detection
      offers to potential for reducing false positive or false negative results in
      screening assays, because of its ability to detect the presence of impurities
      that absorb poorly in the UV (e.g., those impurities originating from the
      polymeric support). Furthermore, the evaporative light-scattering detector
      exhibits a nearly equivalent response to compounds of similar structural class.
      Hence, rapid quantitation of compound libraries may be carried out with the use
      of a single external standard. For example, the quantitation errors, based on a
      single external standard, for a series of steroids, hydantoins, and BOC- and Fmoc
      protected amino acids by normal-phase HPLC with evaporative light-scattering
      detection average approximately +/-10%. The application of the evaporative light
      scattering detector to the quantitation of low-level sample impurities and the
      detector's compatibility with gradient elution are also described.

PMID- 9237217
TI  - Identification of cyclized calmodulin antagonists from a phage display random
      peptide library.
AB  - To isolate peptide ligands that bound calmodulin (CaM) specifically, we screened
      an M13 phage library displaying cyclized octamer random peptides with immobilized
      bovine CaM. Isolates were recovered, sequenced, and deduced to express nine
      independent peptides, five of which contained the sequence Trp-Gly-Lys (WGK).
      Four of the nine peptide sequences were synthesized in cyclized, biotinylated
      form. All of the peptides required Ca2+ to bind CaM. The cyclized, disulfide
      bonded form of one such peptide, SCLRWGKWSNCGS, bound CaM better than its reduced
      form or an analogue in which the cysteine residues were replaced by serine. The
      cyclized peptide also exhibited the ability to inhibit CaM-dependent kinase
      activity. Systematic alanine substitution of residues in this peptide sequence
      implicate the tryptophan residue as being critical for binding, with other
      residues contributing to binding to varying degrees. Cloning of ligand targets
      (COLT) confirmed the specificity of one of the cyclized peptides, yielding full
      length and C-terminal CaM clones, in addition to a full-length clone of troponin
      C, a CaM-related protein. This study has demonstrated that conformationally
      constrained peptides isolated from a phage library acted as specific, Ca(2+)
      dependent CaM ligands.

PMID- 9237218
TI  - Discovery of a herbicidal lead using polymer-bound activated esters in generating
      a combinatorial library of amides and esters.
AB  - A combinatorial library containing mixtures of amides and esters was prepared
      through solid-phase chemistry. The advantages of using solid-phase chemistry over
      solution-phase chemistry to prepare this library are discussed. The library was
      screened through a high-throughput whole organism herbicidal assay upon which a
      mixture containing amides was found to have herbicidal activity. Deconvolution of
      the mixture provided N-(3-benzoylphenyl)-3-(1,1-dimethylethyl)-1-methyl)-1 H
      pyrazole-5-carboxamide as a herbicidal lead with broadleaf and narrowleaf pre
      emergence herbicidal activity as low as 100 g/ha on some weed species. This study
      represents the first report of an agrochemical discovered using a combinatorial
      approach.

PMID- 9237219
TI  - Automating combinatorial chemistry: a primer on benchtop robotic systems.
AB  - Benchtop robotic systems are inexpensive, flexible automation tools with
      potential applications in a wide array of disciplines such as combinatorial
      chemistry, high-throughput screening, and genomics. We explain the basic
      components of a benchtop system and explore factors to consider when purchasing
      or customizing a robot, such as automation benefits, vendor selection, and
      current system limitations. Issues involving system specification, software
      design, and hardware customization are then discussed. Additionally, system
      optimization, validation, and support are detailed. Given a properly designed and
      implemented system, the combinatorial laboratory can markedly increase compound
      synthesis and purification.

PMID- 9237220
TI  - Prostaglandin E2 induces inhibin alpha- and beta A-subunit mRNA and secretion of
      dimeric inhibin A in cultured human granulosa-luteal cells.
AB  - Prostaglandins (PG) E2 and F2 alpha are produced by the human corpus luteum in
      significant amounts and they are known to exert local luteotrophic and luteolytic
      effects respectively. The present study determined how PGE2 and PGF2 alpha are
      involved in the regulation of inhibin A, a granulosa cell-derived glycoprotein
      hormone that has an endocrine inhibitory effect on hypophyseal gonadotrophin
      production and a local stimulatory action on thecal cell androgen secretion. The
      effects of PGE2 and PGF2 alpha on inhibin alpha- and beta A-subunit mRNAs levels
      and on the secretion of dimeric inhibin A were studied in cultures of human
      granulosa-luteal cells obtained from patients undergoing an in-vitro
      fertilization programme. We found that PGE2 induced mRNA of inhibin alpha- and
      beta A-subunits in a time- and concentration dependent manner, whereas PGF2 alpha
      had no clear effect. In contrast to the rapidly and transiently induced beta A
      subunit mRNA, alpha-subunit mRNA accumulation was stimulated with slower kinetics
      by PGE2 in a protein synthesis-dependent manner; this was also observed for the
      mRNA of the cytochrome P450scc enzyme. In the medium of cells cultured for 24 h
      with PGE2 (1 x 10(-6) M), 1.3-1.6-fold increase (P < 0.05) above basal values in
      secreted dimeric inhibin A was observed. The results suggest that PGE2 is an
      important inducer of inhibin A production in granulosa cells and that a local
      action of PGE2 may partially explain the increase in circulating inhibin A
      observed during the midluteal phase of the human menstrual cycle.

PMID- 9237221
TI  - Rapid loss of oestrogen and progesterone receptors in human leiomyoma and
      myometrial explant cultures.
AB  - Oestrogen and progesterone are promoters of uterine leiomyoma growth: oestrogen
      receptors (ER) and progesterone receptors (PR) are over-expressed in these
      tumours. Paradoxically, there is a heterogeneity in responsiveness of leiomyoma
      growth to oestrogen and progesterone in culture. In this study, leiomyoma and
      adjacent myometrium were obtained at hysterectomy. The effect of oestrogen and
      progesterone on steroid receptor maintenance was examined using minced explants.
      Quantitative enzyme-linked immunoassay and Northern analysis were performed to
      assess ER and PR protein and mRNA content respectively. There was an
      approximately 75% decrease in ER and PR protein content within 8 h of incubation
      in both leiomyoma and myometrium. The presence or absence of oestrogen and/or
      progesterone had no effect on receptor protein loss. Northern analysis indicated
      a parallel loss of ER and PR mRNA transcripts. These findings suggest that the ER
      and PR expression in leiomyoma may require other extracellular factors. In-vitro
      studies designed to test the effects of sex steroids and their respective
      inhibitors on growth and function of leiomyoma and myometrial cells should
      consider this phenomenon.

PMID- 9237222
TI  - Activation of elements of the phosphatidylinositol pathway in the primate corpus
      luteum by prostaglandin E2.
AB  - The current study was designed to examine the effects of prostaglandin (PG) E2 on
      progesterone production by primate luteal cells collected during the late luteal
      phase. PGE2 inhibited basal and human chorionic gonadotrophin (HCG)-stimulated
      progesterone production (P < 0.01) in late luteal phase corpora lutea. The
      ability of PGE2 to activate a second messenger system (phosphatidylinositol
      pathway) in corpora lutea of rhesus monkeys was also assessed. PGE2 significantly
      increased the accumulation of inositol phosphates (P < 0.05). This stimulation
      was not apparent in the early luteal phase but was manifested in the mid-late
      luteal phase. PGE2 also caused a rapid, yet transient, increase (P < 0.01) in
      intracellular free calcium ion concentrations ([Ca2+]i) in a large proportion of
      primate luteal cells. The proportion of luteal cells that responded to PGE2 with
      an increase in [Ca2+]i was smaller (P < 0.05) in corpora lutea collected during
      the early luteal phase (12%) in comparison with those collected during the latter
      half of the luteal phase (63-66%). Changes in [Ca2+]i in response to PGE2 were
      similar in small and large luteal cells. This study demonstrates that PGE2
      activates elements of the phosphatidylinositol pathway in primate corpora lutea.
      This activation is augmented as the luteal phase progresses. Thus, the inhibitory
      effects of PGE2 on luteal progesterone production observed in the late luteal
      phase are associated with activation of elements of the phosphatidylinositol
      pathway.

PMID- 9237223
TI  - Egg activation induced by osmotic pressure change and the effects of amiloride on
      the cryopreservation of mouse oocytes.
AB  - Activation of oocytes is caused by osmotic pressure change in some species.
      However, cryopreservation of oocytes occurs in the presence of osmotic pressure
      change induced by cryoprotectants. We investigated the effect of 5-(N,N,
      dimethyl)-amiloride (NNDMA), a selective inhibitor of Na+/H+ exchange, on the
      cryopreservation and osmotic activation of mouse oocytes. The percentage (23.2%)
      of degenerate oocytes after cryopreservation in the presence of NNDMA was found
      to be lower than that (39.5%) of untreated oocytes. After thawing, the percentage
      (23.6%) of oocytes which could be fertilized following cryopreservation in the
      presence of NNDMA was significantly higher than that of untreated (18.0%)
      oocytes. These results suggest that amiloride increased the survival rate after
      thawing following cryopreservation. To investigate the effect of NNDMA on oocyte
      activation caused by the cryoprotectant, dimethyl sulphoxide (DMSO) was used to
      induce osmotic pressure change. NNDMA was found to inhibit cortical granule
      exocytosis, the second polar body emission and pronuclear formation which occurs
      upon activation due to osmotic pressure change. It also inhibited the increase in
      phosphorylation of many proteins including 33 and 45 kDa proteins, which occurs,
      during fertilization and chemical oocyte activation. In contrast, protein
      phosphorylation was not inhibited by W7, a calmodulin inhibitor. The actions of
      these inhibitors suggest that oocyte activation induced by osmotic pressure
      change involves a pathway mediated by Na+/H+ exchange which may be distinct from
      the Ca-calmodulin pathway. Amiloride may be a useful drug for increasing the rate
      of survival of cryopreserved oocytes.

PMID- 9237224
TI  - Changes in centrosomal domains during meiotic maturation in the human oocyte.
AB  - The distribution of microtubule organizing centres (MTOC) in the human oocyte was
      examined using the microtubule-active drug, taxol, to promote polymerization.
      Oocytes were obtained from gonadotrophin-stimulated in-vitro fertilization (IVF)
      patients and examined during various phases of meiotic maturation using confocal
      fluorescence microscopy. During the prophase of meiosis I, taxol failed to
      stimulate microtubule nucleation in any region of the cells. Only a few
      microtubules were visible in the oocyte cortex. As the transition from prophase
      to metaphase began, during germinal vesicle breakdown, taxol stimulated the
      appearance of a small number of isolated aster-like arrays of microtubules in the
      cortex, predominantly in regions adjacent to the nucleus. Oocytes treated with
      taxol when they had reached the first meiotic metaphase exhibited a large number
      of aster-like microtubule arrays. These structures were predominantly located in
      the cortical region of the oocyte, but smaller arrays were also visible in the
      endoplasmic areas. There did not appear to be any increased density of asters in
      any particular cortical or endoplasmic region. Oocytes treated with taxol during
      the second metaphase of meiosis exhibited a similar response to the drug as seen
      during metaphase I, Again, the microtubule asters were most prevalent in the
      cortex, with smaller, less dense arrays in the endoplasm. The metaphase spindle
      was also affected by taxol as revealed by increased density and hyperelongation
      of microtubules at the poles of the spindle as compared to untreated oocytes. The
      metaphase plate of chromosomes was highly disrupted by taxol treatment, most
      likely due to the forces generated by microtubule elongation. We conclude that
      the human oocyte develops MTOC as meiotic maturation proceeds beyond the prophase
      I arrest. The first MTOCs are perinuclear, but the number and distribution
      increases widely as the oocytes enter metaphase. We hypothesize that the
      centrosome of the human recruits several MTOC domains for the assembly of the
      meiotic spindles in both meiotic divisions. It is speculated that one or more of
      the non-spindle-associated MTOCs may combine with sperm centrosomal material
      during fertilization to create the complete centrosome needed for embryonic
      mitosis. The widespread distribution of MTOC foci throughout the cortex may
      ensure this recombination regardless of the point of sperm incorporation into the
      oocyte.

PMID- 9237225
TI  - Calcium responses of human oocytes after intracytoplasmic injection of
      leukocytes, spermatocytes and round spermatids.
AB  - Oocyte activation in mammals involves the action of a soluble sperm factor (SSF)
      that enables oocytes to develop a characteristic series of Ca2+ spikes (Ca2+
      oscillations). SSF is also likely to be responsible for the Ca2+ oscillations
      driving oocyte activation after intracytoplasmic sperm injection [ICSI]. With an
      appropriate injection technique, Ca2+ oscillations do not develop spontaneously
      after ICSI but can be triggered by subsequent treatment of sperm-injected oocytes
      with Ca2+ ionophore. Here we show that Ca2+ oscillations, quite similar to those
      developing after ICSI, can be triggered by the ionophore treatment in human
      oocytes previously injected with human round spermatids. In contrast, oocytes
      injected with earlier spermatogenic cell (primary and secondary spermatocytes)
      and with non-germ cells (polymorphonuclear leukocytes) did not develop Ca2+
      oscillations after the ionophore challenge although the subsequent injection of
      SSF did induce typical Ca2+ oscillations in these oocytes. Disintegration of the
      plasma membrane of the injected cells was detected in all cases by transmission
      electron microscopy. Thus, the absence of the typical oscillatory Ca2+ response
      in spermatocyte-injected oocytes was due to the actual deficiency of SSF in the
      spermatocytes rather than to a defective responsiveness of the injected oocytes
      or to the failure of SSF release into the oocyte cytoplasm. The ability of human
      round spermatids to induce a response to calcium in oocytes that is similar to
      that induced by mature spermatozoa may be important for normal embryonic
      development after spermatid conception.

PMID- 9237226
TI  - Is vitronectin the velcro that binds the gametes together?
AB  - Evidence has been presented that the adhesion of human spermatozoa to the oolemma
      is mediated by integrins recognizing the Arg-Gly-Asp sequence (RGD). Fibronectin
      and vitronectin, glycoproteins that contain functional RGD sequences, are both
      present on human spermatozoa, and integrins that recognize these ligands have
      been detected on spermatozoa and eggs. In this work, we studied the effects of
      oligopeptides specifically designed to block fibronectin or vitronectin receptors
      on the interaction of human spermatozoa with zona-free hamster oocytes. GRGDdSP,
      a peptide blocking cell attachment to fibronectin, was without effect, while
      GdRGDSP, which blocks both fibronectin and vitronectin receptors, significantly
      inhibited the binding of human spermatozoa to the oolemma of zona-free hamster
      eggs, in a concentration-dependent manner, over a range 1-100 microM. As these
      experiments suggested that a vitronectin receptor plays a role in sperm-oolemmal
      adhesion, we performed a series of experiments studying the effects of exogenous
      vitronectin, when added to spermatozoa and oocytes, on gamete interactions. Sperm
      oolemmal adherence, as well as sperm aggregation, was promoted by vitronectin,
      over range of 2.2 nM to 1 microM, but only in the presence of calcium ions. We
      propose that vitronectin released during the sperm acrosome reaction is
      recognized by both gametes and plays a role in their adhesion.

PMID- 9237227
TI  - Effect of gastrin-releasing peptide on sperm functions.
AB  - Male infertility can be related to defects in motility, capacitation, acrosome
      reaction, binding and penetration of the zona pellucida. While different in-vitro
      techniques (such as micromanipulation which is complicated and expensive) are
      available for the treatment of male infertility, several pharmacological agents
      have been shown to increase fertilizing capacity under accurate experimental
      conditions. Gastrin-releasing peptide (GRP, the mammalian homologue of the
      amphibian skin peptide bombesin) is present in the reproductive tract and
      expressed by the pregnant ovine endometrium prior to attachment and throughout
      the pregnancy. A bombesin-like peptide resulting from alternate splicing of the
      GRP gene in testis has been detected in primates. In this study, we have tested
      the ability of GRP to enhance human sperm functions such as motility,
      capacitation, zona binding and acrosome reaction. Analysis of sperm motility was
      performed with the ATS 20 computer-assisted semen analysis (CASA) system. Zona
      binding was analysed using intact human unfertilized oocytes and selective
      labelling of spermatozoa with two fluorochromes. Our results did not show any
      positive effect of GRP on these parameters under our experimental conditions.
      However, when GRP at the concentration of 100 nM was added after ionophore
      treatment, the percentage of reacted cells increased. significantly (P < 0.05)
      compared with situations where each agent was used alone. This led us to suppose
      that the role of bombesin in the different stages of fertilization might not
      exclude other unknown factors.

PMID- 9237228
TI  - Nitric oxide synthase and nitrite production in human spermatozoa: evidence that
      endogenous nitric oxide is beneficial to sperm motility.
AB  - The aim of this study was to investigate the presence of nitric oxide synthase
      (NOS) and the production of nitric oxide (NO) by human spermatozoa.
      Immunoreactivity was examined using a polyclonal antibody raised against porcine
      cerebellar nitric oxide synthase and monoclonal endothelial (eNOS) and brain
      (bNOS) antibodies. Using each antibody, NOS was observed localized in the head
      and midpiece regions of the spermatozoon. Immunofluorescence observed for eNOS
      and bNOS was more intense in normozoospermic samples. Sperm motility was assessed
      by computer-assisted semen analysis (CASA) in the presence and absence of NG
      nitro-L-arginine methyl ester (L-NAME; 10(-5)M), and NO synthesis inhibitor or
      tumour necrosis factor (TNF)-alpha (20 IU/ml), a superoxide inducer. In the
      presence of L-NAME, percentage progressive motility, average path velocity (VAP),
      straight line velocity (VSL) and curvilinear velocity (VCL) were significantly
      reduced after 30 min. Sperm viability was not decreased by TNF alpha or L-NAME.
      The accumulation of nitrite (the stable end-product of the NOS/NO pathway) by
      spermatozoa was measured using the Griess reaction. After 8 h, nitrite
      concentrations were lower in asthenozoospermic compared to normozoospermic
      samples. In the presence of TNF alpha, nitrite accumulation was significantly
      reduced in normozoospermic samples. We conclude that NOS is present in human
      spermatozoa and that eNOS and bNOS are abundant in normozoospermic samples.
      Nitric oxide (at endogenous concentrations) appears to be necessary for adequate
      sperm motility.

PMID- 9237229
TI  - Expression of growth hormone receptor in mouse preimplantation embryos.
AB  - Growth hormone (GH) is believed to be involved in reproductive function. Recent
      reports demonstrate the presence of the growth hormone receptors (GHR) in
      reproductive organs and fetal tissues suggesting that the contribution of GH to
      reproductive phenomena may be mediated through GHR. In this study we assessed the
      expression of GHR in mouse preimplantation embryos using immunofluorescent
      staining with a monoclonal antibody directed against GHR. The messenger RNA
      (mRNA) for GHR was investigated in mouse preimplantation embryo by reverse
      transcription-polymerase chain reaction (RT-PCR). The anti-GHR monoclonal
      antibody Mab 263 was detected by immunofluorescent staining after the compaction
      of the morula stage. GHR mRNA transcript was identified in 8-cell stage embryos.
      Our findings indicate that GHR is localized in mouse preimplantation embryos, and
      suggests that GH has a direct effect on preimplantation embryos mediated by GHR.

PMID- 9237230
TI  - Embryonic origin of preimplantation factor (PIF): biological activity and partial
      characterization.
AB  - Preimplantation factor (PIF) is detected in the serum of women shortly after
      fertilization; its origin, however, has not been established. In this study, the
      embryonal origin of PIF was investigated and partial characterization of the
      factor was carried out. Culture media from viable human 2-8-cell stage embryos
      and mouse 2-cell-blastocyst stage embryos were analysed using the
      lymphocyte/platelet binding assay (LPBA). The assay was performed by combining
      culture media with donor O+ type blood-derived lymphocytes/platelets, complement
      and an antibody against CD2. Increased autorosette formation between lymphocytes
      and platelets (> 9%) was an indication for the presence of PIF. In addition, the
      effect of platelet-activating factor (PAF) and chaperonin 10 on PIF activity was
      determined. Partial purification of PIF was carried out using gel filtration and
      reverse-phase high purification liquid chromatography (HPLC), followed by mass
      spectrometry. Culture media of single human viable fertilized oocytes were
      negative for PIF; however, the 10-fold concentrated medium was positive for PIF.
      In medium in which five or more mouse embryos were cultured, PIF activity was
      observed starting at the morula stage and was higher by the blastocyst stage.
      Addition of PAF or chaperonin 10 to the PIF assay did not elicit a specific
      effect on PIF activity. Chromatographic data suggest that PIF activity is due to
      low molecular weight proteins. PIF appears to be a low molecular weight protein
      which is derived from viable preimplantation embryos. It is different from PAF or
      chaperonin 10. Its final characterization will be valuable for better
      understanding of maternal recognition of pregnancy and implantation.

PMID- 9237231
TI  - The molecular genetics of the zona pellucida: mouse mutations and infertility.
AB  - The zona pellucida is an extracellular matrix surrounding growing oocytes,
      ovulated eggs and the preimplantation embryo. After mediating the relatively
      species-specific events of fertilization, the zona pellucida provides a post
      fertilization block to polyspermy and protects the growing embryo as it passes
      down the oviduct. The genes that encode the three zona pellucida proteins (ZP1,
      ZP2, ZP3) have been characterized in mouse and human. The ability to genetically
      manipulate the zona pellucida genes in mouse models has enhanced our knowledge of
      zona pellucida structure and function in vivo and may translate into a better
      understanding of human fertility.

PMID- 9237233
TI  - Involvement of osmo-sensitive calcium influx in human sperm activation.
AB  - Mammalian spermatozoa must undergo capacitation and acrosome reaction before
      fertilization. To date, the precise mechanisms regulating these complex processes
      are not well understood but it is generally agreed that they involve an influx of
      calcium from the extracellular space through, as yet, poorly characterized plasma
      membrane pathways. Here we present evidence for a novel mechanism to increase
      intracellular calcium concentration via a calcium influx pathway activated by
      sperm cell swelling. Activation of this influx pathway by a mild hypo-osmotic
      shock and the ensuing calcium rise are a potent stimulus for sperm acrosome
      reaction. Furthermore, hypo-osmolarity-activated spermatozoa are fully competent
      for oocyte fertilization. During transit along male and, after ejaculation,
      female genital tracts spermatozoa are known to be exposed to extracellular fluids
      of widely different osmolarity; thus osmo-sensitive calcium influx could have a
      crucial regulatory role in the cellular events preceding fertilization.

PMID- 9237232
TI  - The oxidizing agent tertiary butyl hydroperoxide induces disturbances in spindle
      organization, c-meiosis, and aneuploidy in mouse oocytes.
AB  - It has been recently proposed that a concomitant generation of oxidative stress
      of oocytes with increasing maternal age may be a major factor responsible for the
      age-related increase in aneuploid conceptions. As a preliminary step in the
      testing of this hypothesis, we need to confirm that oxidative stress in itself
      can induce errors in chromosome segregation. In order to achieve this goal,
      germinal vesicle (GV)-stage mouse oocytes from unstimulated ICR and (C57BL x CBA)
      F1 hybrid female mice were matured in vitro for 9 h for metaphase I (MI) oocytes
      or 16 h for metaphase II (MII) oocytes in the presence of varying concentrations
      of the oxidizing agent tertiary-butyl hydroperoxide (tBH). MII oocytes from
      (C57BL x CBA) F1 hybrid mice were fixed and C-banded for karyotyping analysis. MI
      and MII oocytes from ICR mice were fixed and stained with the DNA-fluorescent
      probe 4',6-diamidino-2-phenylindole (DAPI) to detect abnormalities in chromosomal
      distribution. Meiosis I and meiosis II spindles from ICR mice were visualized by
      confocal immunofluorescence microscopy. Data from these experiments demonstrate
      that in-vitro exposure of mouse oocytes to tBH during meiosis I reduces the
      length (pole-to-pole distance) and width (diameter at the equator of the spindle)
      of meiosis I and meiosis II spindles. This reduction is associated with an
      increase in the percentage of oocytes showing chromosome scattering and clumping
      on the MII plate, and of aneuploidy (hyperhaploidy) in MII oocytes. However, tBH
      at the concentrations used in the present study has only a minimal negative
      effect on the frequency of meiotic maturation. These results suggest that
      oxidative stress during meiotic maturation in vitro may induce chromosomal errors
      that are undetectable in the living oocyte and whose developmental consequences
      may become manifest after fertilization.

PMID- 9237234
TI  - Biological activity of recombinant human ZP3 produced in vitro: potential for a
      sperm function test.
AB  - The human zona binding test is the most predictive test of sperm function yet the
      availability of human zona severely restricts its clinical use. The primary aim
      of this study was to use a commercially available in-vitro transcription and
      translation system to produce immobilized recombinant human ZP3 (rhuZP3) on
      agarose beads. The biological activity of this preparation was examined using
      sperm binding and the acrosome reaction. Significantly higher levels of sperm
      binding to rhuZP3 beads (n = 12, P < 0.05) compared with controls were observed
      and there was a significant induction (n = 12, P < 0.01) in the acrosome reaction
      after overnight incubation at 37 degrees C in 5% CO2 in air. In conclusion, the
      in-vitro transcription and translation system can produce sufficient quantities
      of purified immobilized biologically active rhuZP3. These preliminary experiments
      will enable further refinements to be made so that a solid-phase sperm function
      test based on rhuZP3 coated beads is likely to be developed in the near future.

PMID- 9237235
TI  - Protein kinase C activation during progesterone-stimulated acrosomal exocytosis
      in human spermatozoa.
AB  - The involvement of protein kinase C (PKC) in exocytosis of the mammalian sperm
      acrosome is still a controversial issue. Work carried out thus far has failed to
      provide direct evidence for the activation of this enzyme upon stimulation with
      natural agonists of acrosomal exocytosis. We have therefore used progesterone
      stimulation of the acrosome reaction in human spermatozoa to clarify this issue.
      In spermatozoa preincubated under conditions known to support capacitation and
      fertilization in vitro, treatment with progesterone caused a time-dependent
      stimulation of phosphorylation of at least eight proteins ranging in size from
      approximately 20-220 kDa. The inclusion of the PKC inhibitors chelerythrine
      chloride or calphostin C reduced the observed phosphorylation in a concentration
      dependent manner. Exogenously supplied phorbol 12-myristate-13-acetate (PMA) or
      the permeant diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (OAG), synthetic
      activators of PKC, also stimulated phosphorylation in preincubated spermatozoa,
      but inclusion of calphostin C diminished the response. Furthermore, the prior
      inclusion of the 1,4-dihydropyridine Ca2+ channel antagonist nifedipine also
      inhibited phosphorylation, suggesting that PKC is activated downstream of Ca2+
      channel opening. Exocytosis triggered by progesterone was significantly inhibited
      by chelerythrine chloride or calphostin C. Both PMA and OAG triggered exocytosis,
      but the inclusion of chelerythrine chloride significantly inhibited the response;
      exocytotic responses were seen only in capacitated cells. These results provide
      the first direct evidence that PKC activation plays a role in the signal
      transduction pathway underlying acrosomal exocytosis in progesterone-stimulated
      capacitated spermatozoa.

PMID- 9237236
TI  - Immunoelectron microscopical distribution of histones H2B and H3 and protamines
      during human spermiogenesis.
AB  - The fine structural distribution of histones H2B and H3, and protamines were
      localized by means of specific antibodies and ultrastructural immunocytochemistry
      in nuclei of human spermatids and spermatozoa. The antibodies were used to detect
      the nuclear basic proteins on section of testis and ejaculated spermatozoa by
      immunoelectron microscopy. A quantitative analysis of labelling density was
      performed on micrographs using an interactive image analysis system. The
      labelling density of somatic-type histones H2B and H3 and of their testis
      specific variants was constant in the nuclei of young spermatids with round
      nuclei (stages 1-2), and then increased in intermediate spermatids (stages 3-4).
      Histone H3 labelling decreased at the end of the elongation phase (stage 5) while
      histone H2B labelling decreased in mature spermatids (stage 6) only. Spermatozoa
      were found to be weakly labelled by the anti-histone antibodies. The first signs
      of labelling of protamines and basic intermediate proteins appeared in spermatid
      nuclei at stage 4, increased further in stage 6 spermatids and persisted in all
      sperm nuclei. The present work shows that histone-to-protamine replacement occurs
      at the beginning of the spermatid maturation phase in human. However, histones
      are partially retained in mature spermatids and sperm nuclei.

PMID- 9237237
TI  - Application of modern molecular techniques to evaluate sperm sex selection
      methods.
AB  - The aim of this paper is to review modern approaches which have been used to
      evaluate sex pre-selection procedures. Two approaches can be used, polymerase
      chain reaction (PCR) and fluorescence in-situ hybridization (FISH). FISH is
      currently the method of choice for evaluating sex selection procedures because:
      (i) FISH accurately identifies the sex chromosome of individual spermatozoa using
      specific probes for the X and Y chromosomes and a two-colour detection system;
      and (ii) large numbers of spermatozoa can be screened in a short period of time.
      Of the published sex pre-selection methods tested using FISH, only flow cytometry
      has been shown to produce a clinically significant enrichment of X- and/or Y
      bearing human spermatozoa. Studies have shown that 12-step Percoll gradients
      produce a slight but clinically insignificant enrichment of X-bearing
      spermatozoa, swim-up techniques do not appear to enrich either X- or Y-bearing
      spermatozoa, and discontinuous albumin gradients do not enrich Y-bearing
      spermatozoa. Despite this evidence, some of these methods continue to be used
      clinically, so it is vital that sex selection methods are properly evaluated
      using reliable methods such as double-label FISH before they are introduced for
      clinical use.

PMID- 9237238
TI  - The incidence and possible relevance of Y-linked microdeletions in babies born
      after intracytoplasmic sperm injection and their infertile fathers.
AB  - Microdeletions linked to deletion intervals 5 and 6 of the Y chromosome have been
      associated with male factor infertility. Members from at least two gene families
      lie in the region containing azoospermia factor (AZF), namely YRRM and DAZ. With
      the advent of intracytoplasmic sperm injection (ICSI), it is possible for men
      with severe male factor infertility to produce a child. The genetic consequences
      of such a procedure have been questioned. This report describes the first study
      of a population (32 couples) of infertile fathers and their sons born after ICSI.
      The objectives were firstly to determine the incidence and map location of Y
      chromosome microdeletions and to compare the frequencies with other population
      studies involving severe male factor infertility, and secondly to formulate a
      working hypothesis concerning developmental aetiology of Y chromosome
      microdeletions. The incidence of microdeletions in the ICSI population was shown
      to be 9.4% (within the range 9-18% reported for populations of severe male factor
      infertility patients). Microdeletions in two out of three affected father/son
      pairs mapped in the region between AZFb and AZFc and the third involved a large
      microdeletion in AZFb and AZFc. Of three affected father/son pairs,
      microdeletions were detected in the blood of one infertile propositus father and
      three babies. Assuming that the gonomes of the ICSI-derived babies are direct
      reflections of those of their fathers germ lines, it is possible that two of
      three infertile fathers were mosaic for intact Y and microdeleted Y chromosomes.
      In such cases, the developmental aetiology of the microdeletion may be due to a
      de-novo microdeletion arising as a post-zygotic mitotic error in the infertile
      propositus father, thus producing a mosaic individual who may or may not transmit
      the deletion to his ICSI-derived sons depending on the extent of primordial germ
      cell mosaicism. In one of three affected fathers, the microdeletion detected in
      his blood was also detected in his ICSI-derived son. In this case the de-novo
      event giving rise to the microdeletion may have occurred due to a post- (or pre-)
      meiotic error in the germ line of this father's normally fertile father (i.e. the
      ICSI-derived baby's grandfather).

PMID- 9237239
TI  - Morphological-cytochemical and molecular genetic analyses of mitochondria in
      isolated human oocytes in the reproductive age.
AB  - Molecular genetic, cytochemical and morphometric analyses have been performed on
      isolated oocytes from 41 women (27-39 years of age) in order to detect mutations
      of mitochondrial DNA (mtDNA), defects of the respiratory chain (ubiquinone
      cytochrome-c-oxidoreductase = complex III; cytochrome-c-oxidase = complex IV) and
      alterations of mitochondrial volume during cellular ageing. Morphometric analyses
      showed an increase in mitochondrial numerical density with age from the mean
      values of 7.36 per micron2 and 6.97 per micron3 up to 30 years to 10.74 per
      micron2 and 11.66 per micron3 in the age group 31-40 years (P < 0.001).
      Similarly, an increase in the mitochondrial profile area from 0.074 per micron2
      in the age group < 30 years to 0.101 per micron2 was noted in the fourth decade.
      The mitochondrial volume fraction was also significantly increased in the elder
      age group. Neither point mutations of mtDNA (nucleotide pairs 3243, 8344) nor the
      common deletion (4977 bp, nucleotide pairs 8482-13460) could be detected. In
      parallel, ultra- and immunocytochemical studies of the complexes III-IV failed to
      reveal functional defects. In conclusion there is an age-related increase in the
      volume fraction of the mitochondria which might reflect subtle changes in the
      oxidative phosphorylation capacity, but is not linked to mutations of mtDNA or
      functional defects of the respiratory chain enzymes in mature human oocytes from
      women of reproductive age.

PMID- 9237240
TI  - Biochemical study of individual zonae from human oocytes that failed to undergo
      fertilization in intracytoplasmic sperm injection.
AB  - Successful intracytoplasmic sperm injection (ICSI) is dependent upon the
      competence of the oocyte to respond to the injection of a spermatozoon in the
      presence of calcium. This study determined if oocytes that failed to become
      fertilized (absence of any pronuclei) failed to undergo cytoplasmic activation,
      as ascertained by an electrophoretic shift in the zona pellucida (zona) protein,
      huZP2. Of 48 zonae individually analysed, 58% did not have a detectable huZP2
      shift. Three patterns were observed. In seven patients, none of the unfertilized
      oocyte huZP2 shifted (16 out of 48); in two, all zonae exhibited a huZP2 shift
      (five out of 48); in eight, there was a mixture of shifted and unshifted (27 out
      of 48) in each case. There was no clear relationship between the presence of the
      huZP2 shift and maternal age, pregnancy outcome, male-factor infertility, or
      fertilization rate. However, in six couples diagnosed as having no detectable
      male-factor infertility, 73% (11 out of 15) of the zonae had unshifted huZP2,
      suggesting that an oocyte defect is involved in some cases of failed
      fertilization after ICSI. One likely cause for the absence of the huZP2 shift is
      a failure of cytoplasmic activation. Since oocytes were injected at metaphase II,
      we hypothesize that some oocytes that failed to fertilize have completed nuclear
      (meiotic) without cytoplasmic maturation.

PMID- 9237241
TI  - Developmental changes in calcium dynamics, protein kinase C distribution and
      endoplasmic reticulum organization in human preimplantation embryos.
AB  - Developmental changes in the Ca2+ dynamics of human zygotes and preimplantation
      embryos were related to changes in the distribution of endoplasmic reticulum (ER)
      and protein kinase C (PKC). The fertilization-induced Ca2+ oscillations were
      typically observed over > 5 h, were ryanodine-sensitive and showed a periphery-to
      centre propagation of Ca2+ waves. At the same time, ER and PKC were accumulated
      in the cell periphery. After the appearance of pronuclei, ryanodine-sensitive
      Ca2+ oscillations of lower amplitude and frequency were observed until the
      pronuclear breakdown. However, Ca2+ waves then began in the perinuclear region,
      in the area of ER and PKC accumulation and spread towards the cell periphery.
      During the second to fourth cell cycle, small sinusoidal Ca2+ fluctuations were
      observed; sparse higher-amplitude Ca2+ spikes, superimposed on these basal
      fluctuations, appeared shortly before cell division. The sinusoidal Ca2+
      fluctuations were asynchronous in individual blastomeres and disappeared
      progressively in arrested embryos. The direction of Ca2+ wave propagation and the
      distribution of ER and PKC were similar to the situation observed in pronuclear
      zygotes. In contrast to the zygotes, ryanodine did not arrest the Ca2+
      oscillations but augmented their amplitude and frequency. These data suggest that
      human pre-embryos use different mechanisms of Ca2+ signalling in the early post
      fertilization period, during the pronuclear development and during cleavage.

PMID- 9237242
TI  - Proto-oncogenes c-jun and c-fos are down-regulated in human endometrium during
      pregnancy: relationship to oestrogen receptor status.
AB  - Oestrogen is the major stimulatory factor in endometrial cell proliferation.
      Animal and in-vitro studies have shown that proto-oncogenes c-fos and c-jun are
      regulated by oestrogen receptor (ER) complex. We have previously shown by
      Northern blot analysis that proto-oncogenes c-fos and c-jun are strongly
      expressed in human proliferative and early to mid-secretory endometrium. In this
      study, we examined the expression of the messenger RNA (mRNA) of the nuclear
      proto-oncogenes c-fos and c-jun in 10 early (6-10 weeks) and 20 term (30-40
      weeks) pregnancy decidua by Northern blotting. In order to investigate the
      relationship between ER and these proto-oncogenes, the ER and progesterone
      receptors (PR) were identified in the same tissue samples by
      immunohistochemistry. When using 30-mer oligonucleotide probes, hardly any
      signals for c-fos and c-jun could be identified either in early or in late
      pregnancy decidua. Nuclear ER staining was intense in the epithelium and stroma
      of proliferative and early to mid-secretory endometrium but was sparsely
      scattered in stroma and lacking in epithelium during early pregnancy. In late
      pregnancy decidua, no positive ER staining was detectable. PR were present in
      abundance both in endometrial epithelium and stroma in proliferative and early
      secretory phase, and clear positive staining remained in stromal cells in late
      secretory phase and throughout pregnancy. The temporal association between
      immunoreactive ERs and the expression of c-fos and c-jun mRNA suggests that the
      activation of both proto-oncogenes is ER-mediated in human endometrium. The down
      regulation of ER is one possible explanation for the repression of these
      immediate early genes during pregnancy.

PMID- 9237243
TI  - Molecular mechanisms regulating human sperm function.

PMID- 9237244
TI  - Capacitation as a regulatory event that primes spermatozoa for the acrosome
      reaction and fertilization.
AB  - Capacitation is defined as the series of transformations that spermatozoa
      normally undergo during their migration through the female genital tract, in
      order to reach and bind to the zona pellucida, undergo the acrosome reaction, and
      fertilize the egg. During this process, extensive changes occur in all sperm
      compartments (head and flagellum; membrane, cytosol, cytoskeleton), factors
      originating from epididymal fluid and seminal plasma are lost or redistributed
      and membrane lipids and proteins are reorganized; ion fluxes induce biochemical
      modifications and controlled amounts of reactive oxygen species are generated;
      spermatozoa develop hyperactivated motility; and complex signal transduction
      mechanisms are initiated. The main purpose of capacitation is to ensure that
      spermatozoa reach the eggs at the appropriate time and in the appropriate state
      to fertilize these eggs, by finely-controlling the rate of the changes necessary
      to prime spermatozoa and by activating all the mechanisms needed for the
      subsequent acrosome reaction. The reversibility of some of the mechanisms leading
      to sperm capacitation may therefore be a very important aspect of the fine
      regulation and perfect timing of this process.

PMID- 9237246
TI  - Biochemistry of the induction and prevention of lipoperoxidative damage in human
      spermatozoa.
AB  - Lipid peroxidation occurs in human sperm cells with damage to the cell plasma
      membrane, leading to loss of cytosolic components and hence to cell 'death'. The
      peroxidation may be induced at high rates in the presence of Fe2+ and ascorbate.
      It occurs at slower rates under physiological conditions as spontaneous lipid
      peroxidation, which has the following characteristics. The rate is constant over
      the time required for complete loss of motility in the cells of the sperm sample;
      one can thus use the time to complete loss of motility (TLM) as a ready measure
      of the rate. Loss of motility occurs at a characteristic extent of lipid
      peroxidation, assayed in terms of production of the peroxidative breakdown
      product, malonaldehyde (MA), that is independent of peroxidation rate. For human
      sperm, this extent corresponds to 0.1 nmol MA/10(8) cells. Human spermatozoa
      possess the anti-lipoperoxidative defence enzymes, superoxide dismutase (SOD) and
      glutathione peroxidase plus glutathione reductase (GPX/GRD). The SOD activity is
      highly variable between human sperm samples while the activities of GPX and GRD
      are rather more constant. The rates of production of superoxide anion, O2-, and
      hydrogen peroxide, H2O2, from human spermatozoa are variable, but their sum
      calculated in O2- equivalents as O2- + 2H2O2 is quite constant. The variability
      arises from the variability in SOD activity: all H2O2 produced is from O2- due to
      the action of SOD. The essential role of SOD as defence enzyme is inferred from
      the observation that TLM of a given sperm sample is directly proportional to the
      SOD activity of that sample. The essential role of GPX/GRD is inferred from the
      observation that inhibition of GPX, either with mercaptosuccinate or with
      complete oxidation of intracellular reduced glutathione, results in a 20-fold
      increase in peroxidation rate. The capacity of the GPX/GRD system appears to be
      limited by the glucose-6-phosphate dehydrogenase-catalysed rate of production of
      NADPH, the required reductive substrate for GRD. Human spermatozoa appear to have
      enough anti-lipoperoxidative defensive capacity for lifetimes long enough for
      fertilization but still short enough for ready removal from the female
      reproductive tract in good time. Too low a defence capacity could lead to male
      infertility.

PMID- 9237245
TI  - The biochemistry of the acrosome reaction.
AB  - The binding of the spermatozoon to the oocyte zona pellucida (ZP) occurs via
      specific receptors localized over the anterior head region of the spermatozoon.
      Zona pellucida binding stimulates the spermatozoa to undergo the acrosome
      reaction resulting in the release of hydrolytic enzymes and in the exposure of
      new membrane domains, both of which are essential for fertilization. We suggest
      that ZP binds to at least two different receptors in the plasma membrane. One (R)
      is a Gi-coupled receptor that activates phospholipase C (PLC) beta 1. The other
      (TK) is a tyrosine kinase receptor coupled to PLC gamma. Binding to R would
      regulate adenylyl cyclase (AC) leading to elevation of cAMP and protein kinase
      (PKA) activation. The PKA activates a voltage-dependent Ca2+ channel in the outer
      acrosomal membrane which releases Ca2+ from the interior of the acrosome to the
      cytosol. This is the first, relatively small, rise in [Ca2+]i (I) which leads to
      activation of the PLC gamma. The products of phosphatidyl-inositol bisphosphate
      (PIP2) hydrolysis by PLC diacylglycerol (DAG) and inositol-trisphosphate (IP3)
      will lead to PKC translocation to the plasma membrane and its activation. PKC
      opens a voltage-dependent Ca2+ channel (L) in the plasma membrane, leading to the
      second (II) higher increase in [Ca2+]i. The Gi or TK can also activate an Na+/H+
      exchanger leading to alkalization of the cytosol. PKC also activates
      phospholipase A2 (PLA2) to generate arachidonic acid (AA) from membrane
      phospholipids. AA will be converted to prostaglandins (PG) and leukotriens (LT)
      by the enzymes cyclooxygenase (COX) and lipoxygenase (LOX) respectively. The
      increase in [Ca2+]i and pH leads to membrane fusion and acrosomal exocytosis.

PMID- 9237247
TI  - Differential display to identify and isolate novel genes expressed during
      spermatogenesis.
AB  - Spermatogenesis is a complex differentiation process in which diverse stage
      specific proteins are co-ordinately expressed. Previously, subtractive
      hybridization and differential hybridization have been used in the identification
      of differentially expressed mRNAs. Although these techniques have been
      successfully used they require large amounts of RNA and are time consuming. To
      overcome these problems we have made use of the recently described mRNA
      differential display technique. The technique is an effective method which can
      identify and separate cDNAs that are differentially expressed between various
      cell-types. By comparing RNA from testes of mature (> 60 days old) and
      prepubertal (15-16 days old) mice we have identified nine differential cDNA bands
      expressed in mature testes. The differential display cDNA band DDC8 was used
      screen a testis cDNA library and the full length cDNA was isolated and sequenced.
      DDC8 cDNA is 1965 bp with an open reading frame of 533 amino acids which codes
      for a predicated hydrophilic protein with a calculated molecular weight of 62.04
      kDa. RNase protection assays indicate DDC8 to be expressed during the postmeiotic
      stages of spermatogenesis and database searches using both nucleotide and amino
      acid sequences show DDC8 to have similarities to structural, cytoskeletal and
      associated proteins.

PMID- 9237248
TI  - Expression of plasminogen activator and inhibitor, urokinase receptor and inhibin
      subunits in rhesus monkey testes.
AB  - The expression and localization of mRNA's for tissue plasminogen activator (tPA),
      urokinase PA (uPA), uPA receptor (uPAR) and inhibin subunits, alpha, beta A and
      beta B in monkey testes was investigated. Using in-situ hybridization with
      digoxigenin-labelled cRNA probes (dig-cRNA), we demonstrated that tPA and
      plasminogen activator inhibitor type 1 (PAI-1) were expressed in testes of both
      immature and mature rhesus monkeys. tPA mRNA was localized predominantly in
      Sertoli cells. Expression level was low in immature testis, increased
      dramatically in the adult and varied with seminiferous cycle. PAI-1 mRNA was
      localized mainly in germ cells except late spermatids. uPA mRNA was expressed
      stage-specifically in Sertoli cells of adult testis. uPA receptor mRNA was
      localized in germ cells of mature testis but not in spermatogonia or late
      spermatids. Assayed by fibrin overlay technique, PA activity in conditioned media
      of purified Sertoli cells (Sc) was negligible, PA activity in media obtained from
      co-cultured Sertoli and Leydig cells (LS), however, was significantly increased,
      although Leydig cells alone were not capable of producing any PA activity.
      Addition of follicle stimulating hormone (FSH) to the incubation medium
      remarkably increased PA secretion in both Sc and LS cultures. Human chronic
      gonadotrophin (HCG) had no significant effect on PA activity in the Sc culture
      but dramatically stimulated PA activity in the co-culture system.
      Dihydrotestosterone (DHT) did not mimic the effect of HCG. PAI-1 activity was
      secreted mainly by germ cells and did not differ between the two culture systems.
      FSH and forskolin inhibited PAI-1 secretion. Inhibin alpha, beta A and beta B
      subunit mRNAs were localized in Sertoli cells of adult monkey testes, with no
      obvious difference in the expression levels. These data suggest that PA/PAI-1 and
      other related factors are expressed in rhesus monkey testis under the control of
      various hormones, seminiferous cycle and cell-cell interactions through paracrine
      or autocrine regulation. Locally generated fibrinolysis may play an important
      role in the process of spermatogenesis.

PMID- 9237249
TI  - The expression of transforming growth factor-beta s and TGF-beta receptor mRNA
      and protein and the effect of TGF-beta s on human myometrial smooth muscle cells
      in vitro.
AB  - In this study we investigated the expression of transforming growth factor-beta
      (TGF-beta) isoform and TGF-beta receptor mRNA and protein, and the effect of TGF
      beta 1-3 on the rate of DNA synthesis and proliferation of human myometrial
      smooth muscle cells in vitro. To determine these, we utilized primary cultures of
      myometrial smooth muscle cells, standard and competitive quantitative reverse
      transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, enzyme
      linked immunoassay, radioreceptor assay, [3H] thymidine incorporation and cell
      proliferation assay. Standard RT-PCR and immunocytochemistry revealed that
      myometrial smooth muscle cells express TGF beta 1-3 and TGF-beta type I-III
      receptor (TGF-beta R) mRNA and protein. Quantitative RT-PCR, using an external
      synthetic RNA standard, indicated that the cells express 10 copies/cell of TGF
      beta 1 and TGF-beta 2, less than one copy/cell of TGF-beta 3 and TGF-beta type
      IR, three copies/cell of type IIIR, and > 200 copies/cell, of TGF-beta type IIR
      mRNA. The cells also synthesized and released TGF-beta 1 at the rate of 7.8 +/-
      0.7 ng/10(6) cells, of which 1.4 +/- 0.2 ng/10(6) cells was in an active form.
      The rate of [3H] thymidine incorporation or proliferation of subconfluent
      quiescent smooth muscle cells was not altered by TGF-beta s (0.1-10 ng/ml) under
      serum-free conditions, nor in the presence of 10% fetal bovine serum (FBS). TGF
      beta 1-3 at 0.25-0.5 ng/ml in the presence of 2% FBS, which induces half maximal
      stimulation of these cells, stimulated the rate (P < 0.05), whereas at higher
      doses it reduced the rate of [3H]-thymidine incorporation compared to the
      controls. The effect of TGF-beta was partially reversible using neutralizing
      antibodies specific to TGF-beta 1, TGF-beta 2 (10 micrograms/ml) or TGF-beta 3 (3
      6 micrograms/ml). TGF-beta s had no significant effect on cell proliferation
      determined by cell counting. The data indicate that human myometrial smooth
      muscle cells express the necessary components of the TGF-beta system, suggesting
      an autocrine/paracrine role for TGF-beta s in myometrium.

PMID- 9237250
TI  - Nature's motility blockers: controlling human sperm motility machinery from the
      outside. Chemical characterization of a peritoneal fluid lipid that induces sperm
      immobilization.
AB  - A molecule isolated from the peritoneal fluids of women undergoing laparoscopy
      for in-vitro fertilization techniques has been chemically characterized and
      identified as 1-palmitic-3-phosphorylcholine (lysophosphatidylcholine, LPC). This
      lipid is able, at physiological concentrations, to completely inhibit sperm
      motility in vitro in a dose-dependent way. Synthetic LPC induced rapid and
      complete arrest of sperm motility when added to sperm suspensions at
      physiological concentrations without any damage to cell membranes. Taken
      together, these results suggest that LPC may represent a previously unrecognized
      in-vivo modulator of human sperm motility.

PMID- 9237251
TI  - Structure of sperm activating protein.
AB  - Serum is used as an additive in the preparation of human spermatozoa for
      fertilization in vitro, as it is superior to other body fluids in supporting
      sperm motility. We recently purified the major sperm activating macromolecule
      present in serum and showed it to be a complex of immunoglobulin and
      apolipoprotein A-I. This complex, which we named sperm activating protein (SPAP),
      has now been further characterized using partial proteolysis in combination with
      different immunological methods. SPAP was shown to interact only with antibodies
      against immunoglobulin G and more specifically with those against IgG4. The
      bacterial expression products C23 and ZZ-T (which bind to specific sites on the
      IgG molecule) bound in similar ways to SPAP as to IgG4 and did not hinder
      proteolytic cleavage of SPAP, indicating that apolipoprotein A-I is not bound
      closely to the binding sites of these proteins. Purified F(ab')2 fragment from
      SPAP was also shown to contain apolipoprotein A-I, and had a higher MW than the
      corresponding fragment from IgG4. Taken together, the most plausible (and in our
      view only possible) structure of SPAP shows an apolipoprotein A-I molecule bound
      in the pocket formed between the Fab arms of an IgG4 molecule. Anti-SPAP
      antibodies visualized by secondary fluorescein isothiocyanate (FITC)-labelled
      antibodies were bound to the postacrosomal part of the spermatozoa, indicating
      that SPAP is specifically bound to this area, and directly interacts with the
      spermatozoa. Based on these and earlier experiments it is speculated that SPAP
      acts in the lower part of the female genital tract. The benefit of SPAP should be
      at its greatest in these regions, and it is also possible that SPAP exerts a
      selection mechanism, as those spermatozoa affected by SPAP acquire increased
      motility, which might be important in order to reach the upper part of the female
      genital tract. Further exploration of the biological role of SPAP may indicate
      its diagnostic and therapeutic possibilities.

PMID- 9237252
TI  - Isolation and characterization of the primary structure of testis-specific L-type
      calcium channel: implications for contraception.
AB  - Therapeutic administration of calcium channel-blocking medications has been
      correlated with reduced mannose receptor expression and iatrogenic human male
      infertility. In this report, we investigate whether the pharmacological activity
      of dihydropyridines, which block calcium influx through voltage-dependent calcium
      channels, contributes to the production of an infertile state. An influx of
      extracellular calcium is an absolute requirement for the initiation of a
      progesterone-stimulated acrosome reaction by human spermatozoa. To determine
      whether dihydropyridines could inhibit progesterone-induced acrosome loss, we
      have studied a protein expressed in rat and human spermatozoa which is related
      both antigenically and by cDNA sequence to the alpha 1 subunit of the rat cardiac
      muscle voltage-dependent calcium channel, which forms the pore of the channel.
      Using reverse transcription-polymerase chain reaction, we have isolated a 2169
      base clone from rat testis mRNA whose sequence was largely identical to that of
      the alpha 1 subunit of the rat cardiac muscle calcium channel, but had an 84 base
      change, attributable to splicing and alternate exon usage. This change inserts a
      peptide cassette encoding an amphipathic membrane-spanning helix that constitutes
      part of the ionic pore of the skeletal muscle calcium channel regulating the
      kinetics of activation of the calcium channel and may serve as an intramembrane
      dihydropyridine binding site. In parallel, human spermatozoa from fertile donors
      were exposed to nifedipine in vitro. Nifedipine inhibited progesterone-stimulated
      calcium influx and subsequent acrosome reactions in human spermatozoa at
      concentrations effective in excitable cells, but required a prolonged time to do
      so. In contrast, progesterone ligand binding was unaffected by nifedipine
      treatment. These data demonstrate that human spermatozoa express an L-type
      calcium channel which is responsive to nifedipine. Assuming sperm calcium
      transport pathways are highly conserved, the slow kinetics by which the blockade
      of the human sperm channel was obtained can be correlated with alterations in
      channel activation and conductance associated with isoform diversity generated by
      alternate splicing as observed in the rat. These data provide unequivocal
      evidence for the presence of functional L-type voltage-dependent calcium channels
      in rat and human spermatozoa. The data also define an altered binding site for
      calcium entry antagonists in this channel and offer a unique target for the
      design of new male contraceptive agents.

PMID- 9237253
TI  - Sperm factor: what is it and what does it do?
AB  - There are two current hypotheses as to how the spermatozoon triggers the oocyte
      into activity; a transmembrane receptor mechanism involving G-proteins and a
      soluble sperm-factor mechanism. In this short review we show that the present
      data favours the idea of a soluble factor diffusing from the spermatozoon into
      the oocyte following plasma membrane fusion of the two gametes that triggers
      calcium release in the oocyte. Two categories of calcium release mechanisms,
      inositol-1,4,5-triphosphate-induced calcium release (IICR) and calcium induced
      calcium release (CICR) are found in oocytes from a variety of species and both
      appear to be activated at fertilization. Since these calcium release pathways are
      distinct it is possible that sperm cytosol contains more that one activating
      factor. Finally, the fact that sperm extracts 'activate' oocytes from different
      phyla and trigger calcium oscillations in somatic cells infers calcium releasing
      agents common to other cell types.

PMID- 9237254
TI  - Adhesiveness of the free surface of a human endometrial monolayer for trophoblast
      as related to actin cytoskeleton.
AB  - Adhesiveness of the apical (free) plasma membrane of uterine epithelial cells for
      trophoblast is essential for the process of human embryo implantation. As
      epithelial cells are normally repellent, i.e. apically non-adhesive, we argue
      that a remodelling of the epithelial organization from a polarized to a non
      polarized phenotype might prepare the apical pole for cell-cell adhesion during
      the so-called receptive phase. To identify details of apical adhesiveness we
      examined human epithelial RL95-2 cells (RL cells) which, in contrast to other
      cell lines, allow trophoblast to adhere to their apical plasma membrane. To
      determine whether the cytoskeletal structure is functionally critical for
      adhesiveness for trophoblast, RL cells were treated with actin depolymerizing
      cytochalasin D, i.e. 0.4 microM for 120 min. Changes in adhesiveness for
      trophoblast were monitored with a centrifugal force-based adhesion assay.
      Moreover, ultrastructural features, organization of the actin network and
      expression of integrins, i.e. alpha 6, beta 1, beta 4, were studied using
      electron microscopy, confocal laser scanning microscopy and cell surface
      immunogold-labelling techniques. Changes in transmission of mechanical signals
      via integrins into uterine cells were examined using a magnetic drag force
      device, thereby monitoring intracellular calcium responses. The results suggest
      that adhesiveness of the free surface of RL cells for human trophoblast requires
      an intact but non-polarized actin cytoskeleton, apically localized integrins
      linked to actin, and calcium signalling originating at the free surface.

PMID- 9237255
TI  - Nitric oxide inhibits steroidogenesis in cultured porcine granulosa cells.
AB  - Recent evidence suggested that nitric oxide (NO) acts as an important factor in a
      variety of physiological and pathological roles, including reproductive
      functions. The purpose of the present study was to investigate whether NO might
      significantly induce any change in steroidogenesis in cultured porcine granulosa
      cells (PGC). An NO donor, NOC18, significantly suppressed the oestradiol release
      from basal (unstimulated) and gonadotrophin-stimulated PGC in a 2 h culture.
      NOC18 also significantly inhibited the aromatase activity of basal and
      gonadotrophin-stimulated PGC as measured by a modified tritiated water method.
      However, the cGMP analogue, 8-bromo-cGMP, had no significant effect on the
      accumulation of oestradiol and progesterone in basal and gonadotrophin-stimulated
      PGC during 24 h culture. An NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine
      (LNMMA), significantly stimulated the basal oestradiol release and dose
      dependently enhanced the oestradiol and progesterone release from follicle
      stimulating hormone (FSH)-stimulated PGC in a 24 h culture. However, NG
      monomethyl-D-arginine, which does not inhibit NOS, did not enhance the release of
      oestradiol and progesterone under the same experimental conditions. LNMMA also
      significantly suppressed the nitrite concentrations in the media as measured by
      chemiluminescence. These results demonstrate for the first time that NO inhibits
      oestradiol secretion independent of cGMP by inhibiting P450 aromatase activity in
      moderately mature PGC.

PMID- 9237256
TI  - Tetrahydrobiopterin preferentially stimulates activity and promotes subunit
      aggregation of membrane-bound calcium-dependent nitric oxide synthase in human
      placenta.
AB  - Type III nitric oxide synthase (NOS III) is responsible for > 90% of nitric oxide
      (NO) synthesizing activity in first trimester placentae. Enzyme activity is
      distributed between cytosolic (30%) and membrane-bound forms (70%), with highest
      specific activity observed in microsomal fractions. In the present study, the
      effect of tetrahydrobiopterin (BH4) on subunit structure and activity of
      microsomal and cytosolic NOS III was compared. As revealed by immunoblot
      analysis, incubation of microsomal membranes with 50 microM final concentration
      BH4 for 10 min at 37 degrees C resulted in a striking conversion of monomeric NOS
      III into a protein having the characteristics (electrophoretic mobility,
      resistance to sodium dodecyl sulphate) of the homodimeric form. In contrast, BH4
      induced significantly less marked changes in the NOS III dimer content of
      cytosolic fractions. Enzyme activity in microsomes is stimulated approximately 6
      fold upon addition of 50 microM BH4, while only a 2-fold activation is detectable
      in cytosolic fractions. Taken together, the observations suggest that BH4
      activates NOS III in the primordial human placenta by promoting its subunit
      assembly in the membrane, while cytosolic NOS III is relatively insensitive to
      BH4. Compartment-specific action of BH4 represents a novel mechanism which is
      implicated in the regulation of placental NOS activity.

PMID- 9237257
TI  - Expression of syndecan-1 in female reproductive tract tissues and cultured
      keratinocytes.
AB  - The syndecans form a family of cell surface heparan sulphate proteoglycans, which
      participate in cell-matrix interaction and growth factor binding. The expression
      of syndecan-1 was studied in tissues of the female reproductive tract with
      respect to the menstrual cycle, and in cultured vaginal and ectocervical
      keratinocytes. Immunohistochemical localization of syndecan-1 showed a clear
      biphasic pattern, with intense staining in the basal cell layer of vaginal and
      ectocervical epithelium in the proliferative phase, and minimal staining in the
      secretory phase. Low concentrations of syndecan-1 protein and mRNA were expressed
      in endometrium throughout the cycle. In cultured keratinocytes isolated from
      vaginal and ectocervical epithelium, the addition of physiological amounts of 17
      beta-oestradiol or progesterone, alone or in combination, failed to produce
      significant changes in syndecan-1 expression. The cyclic changes of syndecan-1
      localization in stratified epithelia of vagina and ectocervix observed in this
      study may be a result of growth factor action rather than a direct sex steroid
      regulation.

PMID- 9237258
TI  - Isolation and characterization of human and rabbit sperm tail fibrous sheath.
AB  - Using mechanical and chemical dissection methods, fibrous sheath was isolated
      both from normal ejaculated human spermatozoa and from rabbit cauda epididymal
      spermatozoa. The same techniques did not produce a pure preparation of fibrous
      sheath from ejaculated rabbit spermatozoa, suggesting that further cross-linking
      and stabilization of sperm structures occurs in response to components of the
      seminal plasma. The isolation procedures were monitored by phase contrast
      microscopy and the purity of the fibrous sheath was verified by electron
      microscopy. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)
      of isolated human fibrous sheath revealed at least 14 protein bands of which the
      most intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5
      kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which the
      most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid composition
      of the purified fibrous sheath from human and rabbit spermatozoa was similar,
      being high in aspartic acid and/or asparagine and glutamic acid and/or glutamine,
      serine, alanine, leucine, lysine and glycine, but low in histidine, tyrosine and
      isoleucine. This composition is similar to that reported for the rat and suggests
      that mammalian sperm tail fibrous sheaths are composed of similar types of
      proteins, although there are apparent differences in protein components between
      species.

PMID- 9237259
TI  - Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG
      production.
AB  - Women with recurrent abortion, primary unexplained infertility, and gestational
      trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin
      (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene
      complex could cause aberrant HCG production in these disorders. The purpose of
      this study was to determine whether HCG beta gene deletions occur in women with
      recurrent abortion or primary unexplained infertility, and whether HCG beta gene
      duplications are present in women with GTN. DNA was extracted from 10 patients
      with unexplained recurrent abortion, 10 patients with unexplained primary
      infertility, 12 patients with GTN, three partners of women with GTN, and 30
      controls. Southern blots were constructed and hybridized with DNA probes for HCG
      beta-5 and the LH beta gene. No gene deletions were identified in patients with
      recurrent abortion or primary unexplained infertility. Likewise, no gene
      duplications were identified in women with GTN. A previously described Mbol
      restriction fragment length polymorphism (RFLP) was identified in both patients
      and controls. A new Pstl RFLP was also characterized, but was present in patients
      and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex
      do not appear to be common causes of aberrant HCG production in humans with these
      disorders.

PMID- 9237260
TI  - Genomic imprinting: potential function and mechanisms revealed by the Prader
      Willi and Angelman syndromes.
AB  - The Prader-Willi (PWS) and Angelman (AS) syndromes are two clinically distinct
      syndromes which result from lack of expression of imprinted genes within
      chromosome 15q11-q13. These two syndromes result from 15q11-q13 deletions,
      chromosome 15 uniparental disomy (UPD), imprinting centre mutations and, for AS,
      probable mutations in a single gene. The differential phenotype results from a
      paternal genetic deficiency in PWS patients and a maternal genetic deficiency in
      AS patients. Within 15q11-q13, four genes (SNRPN, IPW, ZNF127, FNZ127) and two
      expressed sequence tags (PAR1 and PAR5) have been found to be expressed only from
      the paternally inherited chromosome, and therefore all must be considered
      candidate genes involved in the pathogenesis of PWS. A candidate AS gene (UBE3A)
      has very recently been identified. The mechanisms of imprinted gene expression
      are not yet understood, but it is clear that DNA methylation is involved in both
      somatic cell expression and inheritance of the imprint. The presence of DNA
      methylation imprints that distinguish the paternally and maternally inherited
      alleles is a common characteristic of all known imprinted genes which have been
      studied extensively, including SNRPN and ZNF127. Recently, several PWS and AS
      patients have been found that have microdeletions in a region upstream of the
      SNRPN gene referred to as the imprinting centre, or IC. Paternal IC deletions in
      PWS patients and maternal IC deletions in AS patients result in uniparental DNA
      methylation and uniparental gene expression at biparentally inherited loci. The
      IC is a novel genetic element which controls initial resetting of the parental
      imprint in the germline for all imprinted gene expression over a 1.5-2.5 Mb
      region within chromosome 15q11-q13.

PMID- 9237261
TI  - The progressive rise in the expression of alpha crystallin B chain in human
      endometrium is initiated during the implantation window: modulation of gene
      expression by steroid hormones.
AB  - Human endometrium undergoes sequential changes during the menstrual cycle and
      becomes receptive to implantation during a defined period in the secretory phase.
      We attempted to identify the genes expressed during this period by
      representational difference analysis (RDA). When the cDNAs of a proliferative
      endometrium were used as the driver and the cDNAs of a post-ovulatory day 5
      endometrium were used as the tester, a number of bands were identified by RDA.
      DNA of the cloned RDA products revealed that the majority of the clones contained
      a fragment of a cDNA identical to that of a crystallin B chain. Northern blot
      analysis showed that the expression of the alpha crystallin B chain mRNA was
      absent during the proliferative phase. The expression of the mRNA of alpha
      crystallin B chain first appeared in the secretory phase, progressively increased
      during this phase and peaked in the late secretory endometria. The pattern of
      expression of alpha crystallin B chain mRNA in the endometrium of mature cycling
      baboons (Papio anubis) was similar to that seen in human endometrium. As revealed
      by Western blot analysis, the expression of the alpha crystallin B chain protein
      in human endometrium followed a pattern of expression similar to its mRNA. At the
      cellular level, the immunoreactive protein first appeared in the surface
      epithelial cells of human endometrium within the implantation window without
      significant immunoreactivity in the underlying glandular cells. During the mid-
      and late secretory phases, the intensity of staining in the epithelial cells was
      enhanced and an intense immunoreactivity was developed in the glandular
      epithelium, alpha crystallin B chain was virtually an epithelial product and no
      immunoreactivity for this protein was detectable in the stromal cells,
      endothelial cells or lymphoid cells. The expression of alpha crystallin B chain
      could be regulated, by medroxy progesterone acetate as well as by oestrogen
      withdrawal, in human endometrial carcinoma cells (EnCa-101), transplanted to nude
      mice. Based on the data presented here, the known function of alpha crystallin B
      chain and its distinct pattern of expression in human endometrium, we suggest
      that this protein is an important factor within the molecular repertoire that
      makes endometrium receptive to implantation.

PMID- 9237262
TI  - Insulin-like growth factor binding protein concentration and post-translational
      modification in embryological fluid.
AB  - Levels of proteolytic activity directed against insulin-like growth factor
      binding protein 3 (IGFBP-3) and the distribution of phosphorylated isoforms of
      IGFBP-1 were assessed in matched sample sets of maternal serum, coelomic fluid
      and amniotic fluid from 21 pregnancies at 6-12 weeks gestation. In addition,
      concentrations of immunoreactive IGFBP-1 to -3, insulin-like growth factor (IGF)
      I and -II were determined in all three compartments in 21 pregnancies, and in
      coelomic fluid and maternal serum in 58 pregnancies. IGF-I concentrations were
      highest in maternal serum and similarly low in coelomic and amniotic fluid. IGF
      II concentrations were also highest in maternal serum but easily detectable in
      coelomic fluid where concentrations showed a significant correlation with
      gestational age. IGFBP-1 concentrations were higher in coelomic fluid than in
      either maternal serum or amniotic fluid and showed a significant correlation with
      gestational age in this compartment. Analysis of IGFBP-1 phosphoforms showed
      clear differences in phosphorylation of IGFBP-1 between groups with maternal
      serum containing predominantly the phosphorylated forms and coelomic fluid almost
      exclusively the non-phosphorylated form. First trimester amniotic fluid IGFBP-1
      was barely detectable and appeared non-phosphorylated. These findings suggest
      that the high IGF-II concentrations and lack of inhibitory phosphoforms of IGFBP
      1 in coelomic fluid could potentially enhance mitogenic activity in the early
      human gestational sac. IGFBP-2 concentrations were high in coelomic fluid
      compared with maternal serum whereas coelomic fluid IGFBP-3 concentrations were
      intermediate, easily detectable and correlated strongly with gestational age.
      Protease activity was far less in coelomic fluid than in matched maternal serum
      samples. Marked differences in both concentrations and post-translational
      modification of IGFBPs in maternal serum compared with embryonic fluid suggest
      different regulatory pathways.

PMID- 9237264
TI  - Quantification of hexokinase mRNA in mouse blastocysts by competitive reverse
      transcriptase polymerase chain reaction.
AB  - Hexokinase (HX), the enzyme that catalyses the initial reaction in glycolysis, is
      an important enzyme in glucose metabolism during human and mouse embryonic
      development. In our previous investigations of the genetic activities of HX, we
      observed an increased incidence of HX gene expression in blastocysts in
      comparison with morulae, and variability in the incidence of HX gene expression
      between embryos at the same developmental stages. These observations prompted us
      to quantify HX mRNA in mouse blastocysts to define the biological significance of
      the variable gene transcription. We modified our qualitative reverse
      transcription-nested polymerase chain reaction (RT-nPCR) assay for HX mRNA in
      single or groups of embryos to quantify HX mRNA by competitive RT-nPCR. HX mRNA
      was quantified in cohorts of mouse blastocysts cultured in glucose/phosphate
      containing human tubal fluid (HTF) media. These blastocysts expressed HX in
      minute amounts, averaging 1.95 x 10(-18) g of mRNA. This is the first attempt at
      quantification of single gene mRNA in preimplantation embryos. Further
      investigations using similar techniques will enable comparative analyses between
      embryos to be performed to determine the correlation between specific levels of
      HX mRNA transcripts in individual embryos and embryonic viability and competence
      for further development and implantation.

PMID- 9237263
TI  - Genetic expression of hexokinase and glucose phosphate isomerase in late-stage
      mouse preimplantation embryos: transcription activities in glucose/phosphate
      containing HTF and glucose/phosphate-free P1 media.
AB  - In mouse and human preimplantation development, pyruvate is consumed
      preferentially during early embryogenesis; however, during the morula and
      blastocyst stages, glucose is the preferred energy substrate. Studies have
      suggested that the glycolytic enzymes, hexokinase and glucose phosphate
      isomerase, are important enzymes in glucose metabolism during these later stages
      of human and mouse preimplantation development. In order to investigate the
      genetic activities of these enzymes in late-stage mouse embryos developing in
      vitro, we analysed hexokinase and glucose phosphate isomerase transcription
      activities by qualitative RNA assays using reverse transcriptase-nested
      polymerase chain reaction amplification of individual mouse morulae and early
      blastocysts incubated in glucose/phosphate-free preimplantation stage one (P1)
      medium and glucose/phosphate-containing human tubal fluid (HTF) medium. We
      observed an increased incidence of hexokinase transcripts in the population of
      blastocysts compared with morulae, and differences in transcript incidence
      between early blastocysts developing in HTF medium and in P1 medium. In contrast,
      glucose phosphate isomerase transcripts were consistantly present in all embryos
      analysed, and appear to be constitutively expressed during late-stage mouse
      embryogenesis. The different activity patterns of the two glycolytic genes may
      reflect different mechanisms of gene regulation or differential transcript
      stability during the later stages of mouse preimplantation development.

PMID- 9237265
TI  - Human sperm cytosolic factor triggers Ca2+ oscillations and overcomes activation
      failure of mammalian oocytes.
AB  - Among the possible mechanisms of oocyte activation after sperm penetration, it
      appears most likely that a protein released by the spermatozoon elicits a calcium
      elevation in the ooplasm. To further test this idea, cytosolic factors obtained
      from human spermatozoa by two different methods, freezing-thawing and sonication,
      were injected into mouse oocytes following which intracellular calcium release
      was measured. Of a total of 42 mouse oocytes, a pattern of calcium oscillations
      was observed in nine out of 16 oocytes injected with sonicated fraction, in all
      of eight oocytes with the frozen-thawed fraction and in none of 18 control
      oocytes. Injection of the frozen-thawed fraction also produced regular calcium
      oscillations in all of five in-vitro matured human oocytes. To assess the
      putative factor's ability to support fertilization, human oocytes that were not
      activated by prior intracytoplasmic injection of spermatozoa (ICSI) and round
      spermatids were reinjected with the frozen-thawed sperm fraction. Of 23 human
      oocytes which remained unfertilized after ICSI, 19 became activated after
      injection with sperm cytosolic factor; eight showed two pronuclei, three one
      pronucleus and eight showed three or more pronuclei. Of 11 oocytes unfertilized
      after prior round spermatid injection, two developed two pronuclei, four
      developed one pronucleus and two had three or more pronuclei. Cytogenetic
      analysis by fluorescence in-situ hybridization confirmed the existence of a male
      pronucleus in eight out of nine such zygotes displaying two or more pronuclei.
      Thus, human sperm extracts activated mouse and human oocytes after injection, as
      judged by calcium flux patterns in conjunction with male pronucleus formation.

PMID- 9237266
TI  - Systemic, but not intraparenchymal, administration of 3-nitropropionic acid
      mimics the neuropathology of Huntington's disease: a speculative explanation.
AB  - The mitochondrial toxin, 3-nitropropionic acid, has been introduced in recent
      years as a neurotoxin that can be administered systemically to model the many
      neurobehavioral correlates of Huntington's disease. In this update article, we
      discuss some of the many findings from experiments using the systemic 3
      nitropropionic model, and provide some speculative explanations supporting this
      model over those utilizing conventional excitotoxins or direct intrastriatal
      application of 3-nitropropionic acid. We infer from our own studies and those of
      others that the slow process of neurodegeneration, probably through apoptotic
      mechanism, and the progressive locomotor dysfunctions (from dyskinesia to
      akinesia) inherent in Huntington's disease can be accomplished by chronic, low
      dose systemic administration of 3-nitropropionic acid in rodents as well as in
      non-human primates. This 3-nitropropionic acid model offers a new venue for
      investigating experimental treatment strategies for Huntington's disease.

PMID- 9237267
TI  - Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient
      of ginseng root.
AB  - Our previous study showed that the oral administration of red ginseng powder
      before but not after transient forebrain ischemia prevented delayed neuronal
      death in gerbils, and that a neuroprotective molecule within red ginseng powder
      was ginsenoside Rb1. However, it remains to be clarified whether or not
      ginsenoside Rb1 acts directly on the ischemic brain, and the mechanism by which
      ginsenoside Rb1 protects the ischemic CA1 neurons is not determined. Without
      elucidation of the pharmacological property of ginsenoside Rb1, the drug would
      not be accepted as a neuroprotective agent. The present study demonstrated that
      the intracerebroventricular infusion of ginsenoside Rb1 after 3.5 min or 3 min
      forebrain ischemia, precluded significantly the ischemia-induced shortening of
      response latency in a step-down passive avoidance task and rescued a significant
      number of hippocampal CA1 neurons from lethal ischemic damage. The
      intracerebroventricular infusion of ginsenoside Rb1 did not affect hippocampal
      blood flow or hippocampal temperature except that it caused a slight increase in
      hippocampal blood flow at 5 min after transient forebrain ischemia. Furthermore,
      ginsenoside Rb1 at concentrations of 0.1-100 fg/ml (0.09-90 fM) rescued
      hippocampal neurons from lethal damage caused by the hydroxyl radical-promoting
      agent FeSO4 in vitro, and the Fenton reaction system containing p
      nitrosodimethylaniline confirmed the hydroxyl radical-scavenging activity of
      ginsenoside Rb1. These findings suggest that the central infusion of ginsenoside
      Rb1 after forebrain ischemia protects hippocampal CA1 neurons against lethal
      ischemic damage possibly by scavenging free radicals which are overproduced in
      situ after brain ischemia and reperfusion. The present study may validate the
      empirical usage of ginseng root over thousands of years for the prevention of
      cerebrovascular diseases.

PMID- 9237268
TI  - Responses of parabrachial nucleus neurons to chemical stimulation of posterior
      tongue in chorda tympani-sectioned rats.
AB  - Responses of parabrachial nucleus (PBN) neurons (n = 43) to chemical stimulation
      of the posterior tongue were recorded in chorda tympani (CT)-sectioned rats and
      compared with those (n = 45) in CT-intact. The chemical stimuli used were 0.5 M
      sucrose, 0.5 M sodium chloride (NaCl), 0.03 M hydrochloric acid (HCl), 0.01 M
      quinine hydrochloride, and distilled water. These stimuli were applied to an area
      posterior to the intermolar eminence of the tongue. Neurons of CT-sectioned rats
      responsive to the chemical stimuli were located in more caudal areas of the PBN
      compared with those of CT-intact. Numbers of responses to the five stimuli and
      breadth of responsiveness to the four basics were not different between both
      groups of rats. However, average response magnitudes of the neurons in CT
      sectioned rats were lower than those in CT-intact. In both groups of rats, the
      response magnitudes to NaCl and HCl were larger than those to the other three
      stimuli, and responses to NaCl and those to HCl were highly correlated. It is
      suggested that glossopharyngeal fibers responding strongly to acids and salts are
      likely to be the main source of PBN responses from the posterior tongue.

PMID- 9237269
TI  - Dopamine-denervation enhances the trophic activity in striatum: evaluation by
      morphological and electrophysiological development in PC12D cells.
AB  - To evaluate the possibility that dopamine (DA) denervation enhances the trophic
      activity in striatum, normal or DA-depleted striatal tissue extract (N- or L
      extract, respectively) was obtained, and their trophic effects on PC12D cells
      were investigated from the viewpoints of differentiation using morphological and
      electrophysiological analyses. Treatment with N- or L-extract induced neurite
      outgrowth in a concentration-dependent manner, and induced the enlargement of
      cell size. These effects were stronger in L-extract than in N-extract. Cation
      currents were investigated in whole cell patch-clamp mode. Development of cation
      current started with delayed-rectifier type K+ current (IK) and transient type K+
      current (IA), followed by Ca2+ current (ICa) and tetrodotoxin-sensitive Na+
      current (INa). INa was expressed more frequently in L-extract treated cells than
      N-extract treated cells at D7-9. The larger IK amplitude in L-extract treatment
      at D7-9 seemed to be related to the expression of INa. Development of IA was
      similar at any stage for both treatments. ICa development started at D3-5 after
      treatments, and the amplitude and current density were similar in both
      treatments. ICa was strongly blocked by omega-conotoxin GVIA (3 microM),
      indicating that N-type channels were mainly expressed after treatments. The data
      suggests that L-extract has stronger effects to hasten the differentiation of
      PC12D cells than N-extract by promoting the neurite outgrowth, cell enlargement
      and expression of voltage-dependent cation channels, especially INa and IK.

PMID- 9237270
TI  - Event-related brain potentials to unfamiliar faces in explicit and implicit
      memory tasks.
AB  - The purpose of this study was to investigate electrophysiological correlates
      related to the recognition of repeated faces in the intact human by means of
      event-related brain potentials (ERPs). A group of young healthy adults performed
      a continuous face recognition task, in which 240 unfamiliar faces were flashed
      upon a computer screen with 80 of the faces being repetitions. The subjects had
      to classify faces as previously seen and previously unseen faces. The
      concomitantly recorded ERPs from 19 scalp sites revealed a more positive going
      waveform for the correctly classified repeated faces beginning at about 280 ms
      (old/new effect). The same subjects performed a similar task with visually
      presented concrete nouns as stimuli. The old/new effect in this task showed a
      similar distribution, amplitude and onset latency. It is thus concluded that the
      old/new effect is not specific to the materials to be memorized. In contrast, the
      old/new effect in an implicit face repetition experiment (with the detection of
      famous persons being the task) showed a different distribution. It is argued that
      the differential distribution might reflect the different requirements of the two
      tasks (explicit vs. implicit task). Recent interpretations of the old/new effects
      are discussed.

PMID- 9237271
TI  - Arborization pattern of sympathetic preganglionic axons in the rat superior
      cervical and stellate ganglia.
AB  - Anterograde labeling technique with Phaseolus Vulgaris leucoagglutinin (PHA-L)
      was employed to observe how a single preganglionic axon arborizes in the superior
      cervical ganglion (SCG) and stellate ganglion (STG) of rats. PHA-L was injected
      into the intermediolateral nucleus of the spinal cord at the middle point between
      segments T1 and T2, and labeled axons were detected immunohistochemically in
      serial sections. We traced and drew three preganglionic axons over their full
      length in the SCG and STG. In SCG, the labeled axons bifurcated repeatedly and
      extended to a length of 600-700 microns in the rostrocaudal direction, and about
      200 microns in the transverse direction. These three preganglionic axons made 11,
      14 and 11 dense terminal plexus regions along their trajectory. The pattern of
      the most dense terminal plexus corresponded to the pericellular type dendritic
      plexus, one of the plexus patterns of dendritic collaterals of SCG neurons. In
      the STG, the extent of axonal arborization was more variable than that in the
      SCG, ranging from 400 to 800 microns in the rostrocaudal direction and about 400
      microns in the transverse direction. The three analyzed axons made 21, 19 and 20
      dense terminal plexus regions along their trajectory, with a similar pattern to
      those in SCG. These results indicated that there might be a columnar or
      ellipsoidal organization of postganglionic neurons which are innervated by single
      preganglionic axons.

PMID- 9237272
TI  - Transient decrease of HPC-1/syntaxin-1A mRNA in the rat hippocampus by kainic
      acid.
AB  - HPC-1/syntaxin-1A is a neuronal protein of which the mRNA has an immediate early
      gene-like structure in its 3'-untranslated region. Whereas HPC-1/syntaxin-1A
      protein plays a crucial role in neurotransmitter release, little is known about
      HPC-1 gene expression. We demonstrate here that HPC-1 mRNA expression in rat
      hippocampal neurons in vivo decreased 8 h after kainic acid (KA) administration,
      but was restored thereafter. The transient decrease of HPC-1 mRNA upon KA
      administration suggests that the HPC-1 mRNA expression in neurons could be
      altered by excitation by trans-synaptic stimulation.

PMID- 9237273
TI  - Path and target finding of afferents in cerebellar anlagen grafted in the
      cerebellum of adult rats: a Phaseolus vulgaris leucoagglutinin study.
AB  - Cerebellar anlagen from rat embryos were grafted into the cerebellum of intact
      adult rats. Most of the grafts survived and formed 'minicerebella'. The location
      of the grafts were varied, which provided various types of host/graft interface
      in laminar configuration: Hw/Gg, Hw/Gp, Hw/Gm, Hg/Gw, Hg/Gg, Hm/Gw, Hm/Gg, Hm/Gp,
      and Hm/Gm that comprised of the granule cell layer (g), the Purkinje cell layer
      (p), the molecular layer (m), or the white matter (w) of the host (H) or graft
      (G). The manner of entrance of mossy and climbing fibers through the host/graft
      interface and their outgrowth in the graft which has various subset of laminar
      organization of the cerebellum were examined 28-158 days after grafting by means
      of anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) labeling. Each
      cerebellar afferent entered the graft through specific types of interface and
      grew in specific layers. Mossy fibers passed through Hg/Gg and Hw/Gg, grew in Gg,
      and mostly terminated there like normal fibers. Fibers in Gg, though rarely, grew
      further outside Gg like in development. Climbing fibers passed through Hm/Gg,
      Hw/Gg, and Hw/Gm, proceeded in cortical layers, and terminated in Gm. The
      outgrowth of climbing fibers in Gm showed selectivity for the direction of Gm
      with respect to the polarity of Purkinje cells; they permeated Gm to form
      terminal arbors similar to normal in the direction from the side of Purkinje cell
      somata to dendrites but not in the reverse direction. Occasionally a single fiber
      innervated neighboring multiple Purkinje cells. These results indicate that
      mature cerebellar afferents have potential to regrow and innervate the extraneous
      cerebellar anlage by finding paths and targets in a manner similar to normal
      ontogenesis.

PMID- 9237274
TI  - Enzymatic inactivation of enkephalin neurotransmitters in the spinal cord of the
      neonatal rat.
AB  - The possible involvement of enzymatic degradation in the inactivation of
      enkephalins in the spinal cord of neonatal rats was investigated
      electrophysiologically and biochemically. In an isolated spinal cord-saphenous
      nerve preparation, electrical stimulation of the saphenous nerve evoked a slow
      depolarization lasting 20-30 s of the ipsilateral L3 ventral root. This slow
      depolarization was depressed by a mixture of peptidase inhibitors, consisting of
      actinonin (10 microM), thiorphan (0.6 microM), bestatin (10 microM), arphamenine
      B (10 microM) and captopril (10 microM). Naloxone (0.5 microM) not only reversed
      this effect of the mixture of peptidase inhibitors but also potentiated the slow
      depolarization beyond the pre-control level. In an isolated spinal cord
      preparation, electrical stimulation of a lumbar dorsal root evoked a slow
      depolarization of the contralateral ventral root of the same segment. This slow
      depolarization was depressed by application of [Met5]enkephalin in a dose
      dependent manner. This effect of [Met5]enkephalin was markedly potentiated by
      addition of the mixture of peptidase inhibitors. Among the five peptidase
      inhibitors, actinonin, thiorphan or bestatin alone potentiated the depressant
      effect of [Met5]enkephalin, whereas arphamenine B and captopril did not. Membrane
      fractions prepared from neonatal rat spinal cords showed degrading activities for
      [Met5]- and [Leu5]enkephalins and these activities were inhibited by the mixture
      of peptidase inhibitors. Among the five peptidase inhibitors, actinonin and
      thiorphan markedly inhibited the [Met5]enkephalin-degrading activity while
      bestatin was less effective. Arphamenine B and captopril were ineffective. The
      present results suggest that enzymatic degradation by peptidases plays a role in
      the termination of the transmitter action of enkephalins in the neonatal rat
      spinal cord. The present results, together with our previous results on the
      enzymatic degradation of tachykinins in a study in which we used the same
      preparations, suggest that similar but distinct combinations of peptidases are
      involved in the inactivation of enkephalin and tachykinin neurotransmitters.

PMID- 9237275
TI  - Developmental expression of calretinin in the medial basal hypothalamus and
      amygdala from male and female rats.
AB  - Developmental expression of calretinin in the medial basal hypothalamic (MBH) and
      amygdala region was examined by Western analysis. Males displayed significantly
      higher calretinin levels compared to females in the MBH (but not the amygdala) on
      gestational day 19 and 20. These data imply that hormonal factors may regulate
      developmental MBH calretinin expression. In turn, sexually dimorphic brain
      structures might be influenced by calretinin levels that can alter sexually
      dimorphic patterns of steroidogenesis, cellular migration or programmed cell loss
      mechanism(s) during neuronal development by modulating intracellular calcium
      concentrations.

PMID- 9237276
TI  - A 27-kDa matrix receptor from rat brain synaptosomes: selective recognition of
      the Arg-Gly-Asp-Ser domain and unique resistance to calcium-dependent
      proteolysis.
AB  - A 27-kDa protein from adult rat brain synaptosomes was purified by matrix
      affinity chromatography. The matrix receptor interacted with the Arg-Gly-Asp-Ser
      sequence recognized by integrin-type adhesion molecules, and was labeled by
      integrin antibodies. Levels of the 27-kDa species in brain membranes were
      unaffected by proteolysis, however, conventional integrin subunits exhibited
      robust degradation. This unique resistance to proteolysis may allow the new
      matrix receptor to contribute to the stability of synaptic contacts.

PMID- 9237277
TI  - Facilitation of glutamate release in the ventromedial division of the globus
      pallidus during palatable taste stimulation in freely moving rats: real-time
      measurement.
AB  - To make real-time measurements of glutamate in the ventromedial globus pallidus
      (vGP) in rats during free ingestive behavior, a recently developed dialysis
      biosensor was employed. The glutamate level in the vGP increased in response to
      intraoral infusions of various fluids and voluntary ingestion of food pellets.
      Palatable fluids evoked greater responses than unpalatable fluids did, suggesting
      that glutamate in the vGP is involved in ingestive behavior.

PMID- 9237279
TI  - The Peritoneal Dialysis Multicenter Infection Study Project (MISP) under the
      auspices of the International Studies Committee of the International Society for
      Peritoneal Dialysis.

PMID- 9237278
TI  - A neuroanatomical method to assess the integrity of fibers of passage following
      ibotenate-induced damage to the central nervous system.
AB  - In some behavioral-lesion experiments involving animals, ibotenic acid (IBO) is
      used as a means of damaging brain structures. Occasionally one needs to assess
      the status of fibers coursing through the damaged area to determine whether the
      deficits observed are the result of destruction of neurons rather than fibers. In
      such cases, IBO, is considered to be the method of choice since it destroys cell
      bodies but leaves fibers of passage intact. However, if the IBO dose injected in
      a given area is too high, both cell bodies and fibers of passage could be
      damaged. The anterograde and retrograde tracer wheat germ agglutinin-horseradish
      peroxidase (WGA-HRP) is a useful technique to verify that fibers are intact, and
      is a more powerful tool in comparison with a tracer, such as HRP, which has been
      used in previous studies.

PMID- 9237280
TI  - Is CAPD atherogenic?

PMID- 9237281
TI  - Is total creatinine clearance a poor index of adequacy in CAPD patients with
      residual renal function?

PMID- 9237282
TI  - Nursing home dialysis: can we meet the challenge?

PMID- 9237283
TI  - Lipoprotein(a) and apolipoprotein(a) phenotypes in patients with end-stage renal
      disease.
AB  - OBJECTIVE: To evaluate the distribution pattern of apolipoprotein(a) [Apo(a)]
      phenotypes in Koreans and the effect of dialysis modality on serum lipoprotein(a)
      [Lp(a)] concentration according to apo(a) phenotype in patients with end-stage
      renal disease (ESRD). DESIGN: Cross-sectional study. SETTING: A university
      hospital. PARTICIPANTS: 153 normal controls, 99 hemodialysis (HD) patients and 82
      continuous ambulatory peritoneal dialysis (CAPD) patients. MAIN OUTCOME MEASURES:
      Fasting serum Lp(a), lipids, and apo(a) phenotypes were measured. RESULTS: The
      frequencies of the subjects with apo(a) phenotypes of high-molecular weight only,
      including S3, S4, or S5 or null type were 95.4% of control, 100% of HD patients,
      and 95.1% of CAPD patients. The frequent apo(a) phenotypes in Koreans consisted
      of S4, S4S5, S5, and S5S5 isoforms. Significant difference was found in serum
      Lp(a) concentration among controls and HD and CAPD patients [median
      (Interquartile range): 0.05 g/L, (0.01-0.19); 0.19 g/L, (0.10-0.35); 0.63 g/L,
      (0.28-0.90), p < 0.001]. Lp(a) levels in CAPD patients were significantly higher
      than in HD patients for all four common apo(a) isoforms found in Korean subjects.
      CAPD patients had higher total and LDL cholesterol levels, and higher ApoB levels
      than HD patients. Significant differences were found in serum albumin levels
      between controls and HD and CAPD patients (44 +/- 3 g/L, 40 +/- 4 g/L, 32 +/- 7
      g/L, respectively, p < 0.05). There were significant inverse correlations between
      serum albumin and Lp(a) (r = -0.33, p < 0.01), total cholesterol (r = -0.31, p <
      0.01), LDL (r = -0.39, p < 0.01) or ApoB (r = -0.35, p < 0.01) in ESRD patients.
      A significant positive correlation was found between serum albumin and ApoA1 (r =
      0.24, p < 0.01). CONCLUSION: These findings indicate that Koreans have mainly
      high molecular weight apo(a) phenotypes and serum Lp(a) is elevated in CAPD
      patients compared to HD patients for common apo(a) phenotypes, which may
      contribute to the frequent cardiovascular mortality in CAPD patients.

PMID- 9237284
TI  - Residual renal function affects lipid profile in patients undergoing continuous
      ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To determine whether lipoprotein abnormalities associated with
      continuous ambulatory peritoneal dialysis (CAPD) are influenced by residual renal
      function (RRF). DESIGN: Open, nonrandomized prospective and comparative study.
      SETTING: Single university teaching hospital dialysis unit and outpatient clinic.
      PATIENTS: Twenty adult patients on standard CAPD (1-38 months) were divided into
      two groups: group A (RRF < or = 0.8 mL/min, n = 10) and group B (RRF > or = 1.1
      mL/ min, n = 10), Patients in the two groups were matched for age, time on
      dialysis, body weight, body mass index, serum urea and albumin levels, peritoneal
      and urinary albumin losses, and peritoneal transport characteristics such as
      overnight 8-hour peritoneal creatinine and beta 2-microglobulin clearances and
      overnight B-hour effluent glucose concentrations. RESULTS: The degree of uremia
      in patients with preserved RRF (group B) was obviously lower than in patients
      with negligible RRF (group A), that is, patients in group B had significantly
      lower serum creatinine and beta 2-microglobulin levels and significantly higher
      weekly KT/V than group A patients. Despite the prevalence of allele 4 of
      apolipoprotein E genotype in group A patients, their levels of serum total
      cholesterol, low-density lipoprotein cholesterol, lipoprotein (a) [Lp(a)],
      apolipoprotein B(ApoB), and apolipoprotein A1 (ApoA1) were significantly lower
      than those of patients with preserved RRF (group B). The two groups did not
      differ significantly in the serum levels of triglyceride or high-density
      lipoprotein cholesterol. Serum concentrations of Lp(a) and ApoA1, as well as
      ratios of ApoA1 to ApoB, were correlated significantly with RRF (r = 0.63, r =
      0.51, and r = 0.61, respectively). CONCLUSIONS: The findings suggest that RRF
      affects the lipid profile of CAPD patients, especially serum levels of
      cholesterol-rich lipoproteins.

PMID- 9237285
TI  - Estimation of total daily creatinine clearance in CAPD from serum creatinine
      concentration.
AB  - OBJECTIVE: To establish whether estimation of creatinine clearance (CrCl) from
      serum creatinine, gender, age, and weight might reduce the number of 24-hour
      urine and dialysate collections required to monitor adequacy of delivered
      dialysis on continuous ambulatory peritoneal dialysis (CAPD). DESIGN:
      Retrospective single-center study. SETTING: University Hospital. PATIENTS:
      Creatinine excretion and CrCl were measured in 187 24-hour urine and dialysate
      collections from 99 CAPD patients (55 male, 44 female). Multiple regression
      analysis was used to estimate creatinine excretion from age and weight in males
      and females. CrCl was derived and also calculated using the Cockcroft-Gault and
      Mitch-Walser formulas. Positive and negative predictive values for indicating
      adequacy of dialysis were determined. RESULTS: Measured and derived CrCl were
      correlated (males: r = 0.85; females: r = 0.83; p < 0.001), but agreement was
      poor (95% limits of agreement: males, 26.05 to -25.75 L/wk; females, 37.47 to 
      19.49 L/wk). Taking the minimum acceptable CrCl as 60 L/week, the respective
      positive predictive values of the derived, Cockcroft, and Mitch methods in
      predicting underdialysis were 88%, 100%, and 100% in males and 88%, 88%, and 89%
      in females. Negative predictive values were 83%, 57%, and 53% in males and 53%,
      48%, and 45% in females. CONCLUSION: A derived CrCl > 60 was not predictive of
      adequate dialysis. Because the detection of underdialysis is our objective,
      formal clearance studies should be performed in this group. A derived CrCl < 60
      L/wk was predictive of underdialysis in males and females and an increase in
      dialysis dose without formal clearance measurements could be suggested in these
      patients. The use of this approach could allow an important reduction in the
      number of clearance studies required to monitor CAPD adequacy.

PMID- 9237286
TI  - Ten years' experience with CAPD in a nursing home setting.
AB  - OBJECTIVE: We reviewed our experience with end-stage renal disease (ESRD)
      patients treated with continuous ambulatory peritoneal dialysis (CAPD) in a
      nursing home with the aims of describing their demographic and clinical
      characteristics, evaluating CAPD technique success and patients outcomes.
      SETTING: University-based, teaching nursing home. DESIGN: Retrospective review of
      patients in our nursing home treated with CAPD between 1 June 1986 and 1 June
      1996. PATIENTS: One hundred and nine patients: 66 (60.5%) were female and 59
      (54%) were white. Their mean age was 62.7 years +/- 12.8 SD (range 31-88).
      Females were significantly older than males (64.9 years +/- 10.7 SD vs 59.1 years
      +/- 14.6 SD, p < 0.05). Sixty-eight (62.4%) were diabetics. MAIN OUTCOMES
      STUDIED: Cox-adjusted patient survival. Cause of death. Peritonitis and
      hospitalization rates. Logistic analysis of predictors of discharge home.
      RESULTS: Six- and 12-month survival rates were 51.7% and 37.2%, respectively. Age
      greater than 75, poor functional status, coronary artery disease (CAD), and
      decubitus ulcers were significant mortality risks. Vascular disease was the
      leading cause (41.7%) of death. The peritonitis rate in the nursing home was 1.19
      episodes per patient year. Gram-positive organisms predominated. The
      hospitalization rate was 22.4 days per patient year. Gangrene/ stump infections
      and peritonitis accounted for 14% and 10% of admissions. Those patients admitted
      for rehabilitation and with higher activity of daily living (ADL) scores were
      more likely, and those with diabetes, age > or = 75, and CAD less likely to be
      discharged. CONCLUSIONS: We continue to believe that peritoneal dialysis is a
      reasonable option for ESRD patients placed in nursing homes. Technical problems
      do not limit its use, but overall poor patient outcomes are an important issue.
      Patients, their families and referring physicians should be informed of the
      limited survival expectations particularly for the very old and/or severely
      functionally impaired patient. Patients whose discharge is anticipated on
      admission are those most likely to return to the community and are the most
      likely to truly benefit from nursing home placement.

PMID- 9237288
TI  - The diagnostic value of Gram stain for initial identification of the etiologic
      agent of peritonitis in CAPD patients.
AB  - OBJECTIVE: To evaluate the effectiveness of the Gram stain in the initial
      diagnosis of the etiologic agent of peritonitis in continuous ambulatory
      peritoneal dialysis (CAPD). DESIGN: Retrospective study analyzing the sensitivity
      (S), specificity (SS), positive predictive value (+PV), and negative predictive
      value (-PV) of the Gram stain relating to the results of cultures in 149 episodes
      of peritonitis in CAPD. The data were analyzed in two studies. In the first, only
      the cases with detection of a single agent by Gram stain were taken (Study 1). In
      the second, only the cases with two agents in Gram stain were evaluated (Study
      2). SETTING: Dialysis Unit and Laboratory of Microbiology of a tertiary medical
      center. PATIENTS: Sixty-three patients on regular CAPD who presented one or more
      episodes of peritonitis from May 1992 to May 1995. RESULTS: The positivity of
      Gram stain was 93.2% and the sensitivity was 95.7%. The values of S, SS, +PV, and
      -PV were respectively: 94.9%, 53.5%, 68.3%, and 90.9% for gram-positive cocci and
      83.3%, 98.8%, 95.2%, and 95.6% for gram-negative bacilli. The association of gram
      positive cocci plus gram-negative bacilli were predictive of growth of both in
      6.8%, growth of gram-positive cocci in 13.7%, and growth of gram-negative bacilli
      in 72.5%. CONCLUSIONS: The Gram stain is a method of great value in the initial
      diagnosis of the etiologic agent of peritonitis in CAPD, especially for gram
      negative bacilli.

PMID- 9237287
TI  - Predialysis glycemic control is an independent predictor of clinical outcome in
      type II diabetics on continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To evaluate the correlation between predialysis glycemic control and
      clinical outcomes for type II diabetic patients on continuous ambulatory
      peritoneal dialysis (CAPD). DESIGN: Sixty type II diabetic patients on CAPD were
      classified into 2 groups according to the status of glycemic control. In group G
      (good glycemic control), more than 50% of blood glucose determinations were
      within 3.3-11 mmol/L and the glycosylated hemoglobin (HbA1C) level was within 5
      10% at all times. In group P (poor glycemic control), fewer than 50% of blood
      glucose determinations were within 3.3-11 mmol/L or HbA1C level was above 10% at
      least once during the follow-up duration. In addition to glycemic control status,
      predialysis serum albumin, cholesterol levels, residual renal function,
      peritoneal membrane function, and the modes of glycemic control were also
      recorded. SETTING: Dialysis Unit, Department of Nephrology of a single university
      hospital. PATIENTS: From February 1988 to October 1995, 60 type II diabetic
      patients receiving CAPD for at least 3 months were enrolled. MAIN OUTCOME
      MEASURES: Morbidities before and during the dialysis period, patient survival,
      and causes of mortality. RESULTS: The patients with good glycemic control had
      significantly better survival than patients with poor glycemic control (p <
      0.01). There was no significant difference in predialysis morbidity between the
      two groups. No significant differences were observed in patient survival between
      the patients with serum albumin greater than 30 g/L and those with less than 30
      g/L (p = 0.77), with cholesterol levels greater or less than 5.18 mmol/L (p =
      0.73), and with different peritoneal membrane solute transport characteristics
      evaluated by peritoneal equilibration test (p = 0.12). Furthermore, there was no
      significant difference in survival whether the patients controlled blood sugar by
      diet or with insulin (p = 0.33). Cardiovascular disease and infection were the
      major causes of death in both groups. Although good glycemic control predicts
      better survival, it does not change the pattern of mortality in diabetics
      maintained on CAPD. CONCLUSIONS: Glycemic control before starting dialysis is a
      predictor of survival for type II diabetics on CAPD. Patients with poor glycemic
      control predialysis are associated with increased morbidity and shortened
      survival.

PMID- 9237289
TI  - Calculation of 6-hour D/P creatinine ratio from the 4-hour peritoneal
      equilibration test. The effect of dwell duration on the results.
AB  - OBJECTIVES: Since the introduction of the peritoneal equilibration test (PET),
      the 4-hour dialysate/plasma creatinine (D/P Cr) has been used by several authors
      for determining continuous ambulatory peritoneal dialysis (CAPD) prescriptions.
      However, the results have been unsatisfactory because the 4-hr D/P Cr does not
      accurately reflect the D/P Cr in 24-hr collections. The PET and the 24-hr
      dialysate collections differ in the duration of dwell and the tonicity and volume
      of dialysate, all of which influence the equilibrated D/P Cr. It can be assumed
      that the D/P Cr in 24-hr collections in these patients is closer to a 6-hr D/P
      Cr. Because a 6-hr PET is inconvenient, we developed a mathematical model to
      calculate the 5- and 6-hr D/P using the results of a standard PET. DESIGN: In a
      retrospective analysis, D/P Cr ratios in 24-hr collections and D/P Cr ratios
      calculated from a mathematical formula were correlated. Using a mathematical
      model, the data collected fit an exponential relation of the type D/P = a(1-e
      t/tau). The values of a and tau are unique for a given patient and were
      determined using a nonlinear regression technique. The formula performed well on
      our published data-the true and predicted 6-hr D/P Cr being 0.696 and 0.71,
      respectively. SETTING: The University Hospital and Clinics, Dalton Cardiovascular
      Research Center and Dialysis Clinic, Inc., Columbia, Missouri. PATIENTS: All CAPD
      patients on four 2-L exchanges/day at the time of the 24-hr collections were
      included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Closeness of 4-hr and 6-hr
      D/P Cr values to those of 24-hr ratios. RESULTS: The study group comprised 74
      patients (age, mean +/- SEM: 56.4 +/- 1.8 yr) with 80 PETs and 145 (24-hr)
      collections. The interval between the two tests was 8.3 +/- 0.9 months (0-48.7
      months). The median 24-hr D/P Cr of 0.760 did not differ significantly from the
      predicted median 6-hr D/P Cr of 0.755. A subgroup analysis, based on transport
      type, showed that this relationship was most precise in the high-average
      transporters. The predicted 6-hr D/P Cr was within 10% of the 24-hr D/P Cr in 48%
      of patients and within 20% in 77% of patients. The margin of error was greatest
      in the low transporters. CONCLUSIONS: To conclude, the 4-hr D/P Cr from a PET
      cannot be used interchangeably with the D/P Cr in the 24-hr dialysate
      collections, hence, the clearances calculated thereof will be inaccurate. Using
      the proposed model, it is feasible to use the 4-hr PET results to obtain 5- and 6
      hr D/P Cr values. In our study, using this model, the extrapolated 6-hr D/P Cr is
      similar to the D/P Cr in 24-hr dialysate collections only in the high-average
      transporters. Hence, the best way to determine clearances in peritoneal dialysis
      patients is still by collecting 24-hr dialysates.

PMID- 9237290
TI  - Six-month prospective cross-over study to determine the effects of 1.1% amino
      acid dialysate on lipid metabolism in patients on continuous ambulatory
      peritoneal dialysis.
AB  - OBJECTIVE: To evaluate the effect of 1.1% amino acid dialysate (AAD) (Nutrineal,
      Baxter, Castlebar, Ireland) on lipid metabolism in hyperlipidemic patients on
      continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Patients were
      alternately assigned to receive AAD in the first (group A), or the second (group
      B), 6 months of a prospective cross-over study. SETTING: University teaching
      hospital. PATIENTS: Eighteen stable CAPD patients with a serum cholesterol 5.5
      mmol/L or greater. INTERVENTIONS: One post prandial exchange of AAD during a 24
      hour period for 6 months. MAIN OUTCOME MEASURES: A significant change in serum
      lipid levels. RESULTS: Patients in group A (n = 10) received a single daily
      exchange of AAD in place of their post prandial dextrose exchange for the first 6
      months, and then crossed over to the dextrose phase. Patients in group B (n = 8)
      continued their usual dextrose dialysis for the first 6 months and then crossed
      over to receive AAD in the latter 6 months. Measurements of serum lipids and
      lipoproteins along with other biochemical parameters were made at regular
      intervals. Although a downward trend in mean serum total cholesterol was seen on
      AAD in group A, no significant change in total cholesterol, low-density
      lipoprotein cholesterol, or high-density lipoprotein cholesterol was observed in
      any group. Mean serum triglycerides fell on AAD in both groups, but were not
      statistically significant. Serum lipoprotein(a) [Lp(a)] and apolipoprotein B were
      elevated in both groups but did not change on AAD or with time. No change was
      observed in serum apoprotein A1 levels. Serum Lp(a) was not correlated to
      dialysate protein excretion. No change in mean serum albumin was observed, in
      either group, on AAD. KT/V urea, total weekly creatinine clearance, net
      ultrafiltration, and dialysate protein excretion remained unchanged on AAD.
      CONCLUSIONS: The use of AAD, although clinically safe and without side effects,
      had no effect on the dyslipidemia in our group of CAPD patients.

PMID- 9237291
TI  - Calcium metabolism in blood and peritoneal lymphocytes from continuous ambulatory
      peritoneal dialysis patients.
AB  - OBJECTIVE: Cellular immune function in peritoneal dialysis patients has been
      shown to be depressed, but the mechanism of this immunosuppression has not been
      ascertained. Because calcium is an important mediator of lymphocyte activation,
      this study was designed to investigate if there was an alteration of calcium
      metabolism in the lymphocytes of continuous ambulatory peritoneal dialysis (CAPD)
      patients. DESIGN: Sixteen CAPD patients were studied at the initiation of CAPD
      and after two months of treatment. Twenty-three normal controls were also
      enrolled in the study. Cytoplasmic calcium changes were investigated in response
      to the mitogen phytohemagglutinin (PHA) in peripheral blood and peritoneal
      lymphocytes, using the intracellular calcium probe indo-1 and flow cytometry.
      Baseline cytoplasmic calcium levels and changes in cytoplasmic calcium in
      response to PHA were assessed at the initiation of CAPD and after two months of
      therapy. RESULTS: Peripheral lymphocytes of patients and controls had similar
      calcium baseline levels, but the peritoneal lymphocytes had baseline cytoplasmic
      calcium levels averaging 81% higher than the corresponding calcium levels of the
      patients' peripheral blood lymphocytes. As compared to peripheral lymphocytes,
      the response to PHA stimulation was significantly less in the peritoneal
      lymphocytes, increasing an average of only 46.8% above baseline. Peripheral blood
      lymphocytes of the patients responded by an average increase of 78.9% over
      baseline. Control cells increased an average of 66.3% over baseline. Follow-up
      studies done two months after the initiation of CAPD indicated there were no
      significant changes (as compared to month 0) that occurred in baseline or
      stimulated intracellular calcium concentrations. CONCLUSIONS: While the
      peripheral lymphocytes of CAPD patients respond adequately to PHA, the high
      baseline calcium levels of the peritoneal lymphocytes suggest that these cells
      may be in a state of chronic activation and may respond minimally to an antigenic
      challenge.

PMID- 9237292
TI  - Peritoneal surface area and its permeability in rats.
AB  - OBJECTIVE: Evaluation of peritoneal surface area and its permeability during
      dialysis in rats of various ages. DESIGN: Study I: planimetry of peritoneum and
      its topographic areas was performed in 47 rats of various ages (8-30 weeks).
      Study II: net ultrafiltration (UF), dialysate-to-serum ratios for urea,
      creatinine, albumin, and total protein as well as their peritoneal permeability
      coefficients, were measured during a 1-hour peritoneal exchange with Dianeal
      2.5%, in 21 rats of different ages (9-30 weeks) and with various peritoneal
      surface areas. ANIMALS: Male Wistar rats. RESULTS: The peritoneal surface area in
      rats increases during aging, but young animals with lower body weight have a
      relatively larger peritoneal surface area than older, larger animals. The area of
      the topographic fragments of peritoneum expressed as a percentage of the total
      peritoneal surface is steady during aging. Efficiency of transperitoneal water
      removal expressed as net UF per amount of absorbed glucose declines in older
      animals, with larger peritoneal surface areas. Dialysate/serum ratio of solutes
      transported from blood to dialysate is proportional to peritoneal surface area.
      Permeability coefficient (K) of peritoneum to urea and creatinine is unchanged
      during the aging of animals. However peritoneal permeability (K) to albumin
      increases during aging, with the opposite tendency for total proteins.
      CONCLUSIONS: Kinetics of peritoneal dialysis in rats of different ages is
      determined by peritoneal surface area and permeability of peritoneum to
      individual solutes.

PMID- 9237293
TI  - 14-year experience with the double-cuff straight Tenckhoff catheter.

PMID- 9237295
TI  - Emphysematous cholecystitis in a CAPD patient.

PMID- 9237294
TI  - Cross-sectional analyses of non-urea nitrogen appearance (NUNA) in a CAPD
      population.

PMID- 9237296
TI  - Management of lipid abnormalities in patients on CAPD.

PMID- 9237297
TI  - Complications associated with the use of the Swan neck presternal catheter: a
      case report.

PMID- 9237298
TI  - Comparative aspects of cellular-volume regulation in cardiomyocytes.
AB  - All cells possess mechanisms that are responsible for the maintenance of cellular
      volume under isosmotic conditions. In addition, many cells are able to adjust
      cellular volume when incubated in hypo- or hyperosmotic media. Much of the work
      on cellular-volume regulation has been done on epithelial cells, blood cells, or
      lines of cultured cells; cardiac muscle has received comparatively little
      attention. It seems probable that some aspects of cellular-volume regulation in
      cardiomyocytes vary from those present in other cell types because of the
      mechanisms associated with the excitability and contractility of cardiac muscle.
      For example, in myogenic hearts, the role of membrane ion channels in pacemaker
      potentials complicates models that implicate ion channels as mechanisms for
      volume regulation. Similarly, models for the initiation and control of volume
      regulation that rely on changes in cytosolic Ca2+ levels may not be applicable to
      cardiac muscle, where each action potential and contraction involves the release
      of Ca2+ from internal stores and a significant influx of Ca2+ across the plasma
      membrane. A review of the available data on volume regulation in cardiac muscle
      from a variety of invertebrate and vertebrate species suggests that many features
      of the current models proposed for the initiation and control of cellular-volume
      regulation are not compatible with the physiology of cardiac muscle. There are
      large gaps in our knowledge about volume regulation in cardiac muscle, and
      further investigation is clearly necessary to enhance our understanding of this
      aspect of cardiomyocyte physiology.

PMID- 9237299
TI  - Protein metabolism, the costs of growth, and genomic heterozygosity: experiments
      with the mussel Mytilus galloprovincialis Lmk.
AB  - A single cohort of small individuals (31 mm mean shell length, 112 mg mean dry
      flesh weight) of the marine bivalve mollusc Mytilus galloprovincialis Lmk. was
      held sequentially for 2 wk at each of four food levels equivalent to ingested
      rations of less than 0.1%, 2.6%, 3.1%, and 7.4% of dry body weight per day.
      Growth rate reached a maximum at the highest ration level and was strongly
      correlated, amongst individuals, with mean heterozygosity measured across nine
      enzyme loci. Rates of energy expenditure were analysed separately as maintenance
      metabolic rate and the energy costs of growth (J mg-1 dry tissue). The
      maintenance metabolic rate correlated with traits of protein metabolism (protein
      synthesis, deposition, and breakdown), and the separate energy costs of both
      maintenance and growth correlated with the efficiency of protein deposition
      (protein growth as a proportion of synthesis). The energy costs of growth also
      varied in negative relation to mean individual heterozygosity. In a multiple
      regression analysis, the energy allocation to the costs of growth, body size,
      mean heterozygosity, and the efficiency of protein deposition together explained
      90% of the variance amongst individuals in observed rates of growth. The results
      support the hypothesis that individual variability in the energy costs of protein
      turnover and in the efficiency of protein deposition during rapid growth are
      significant factors providing a link between individual genotype and its
      phenotypic expression as growth.

PMID- 9237300
TI  - Thermal sensitivity of Drosophila melanogaster: evolutionary responses of adults
      and eggs to laboratory natural selection at different temperatures.
AB  - We compared aspects of the thermal sensitivity of replicated lines of Drosophila
      melanogaster that had been evolving by laboratory natural selection at three
      selection temperatures: 16.5 degrees C (10+ yr), 25 degrees C (9+ yr), or 29
      degrees C (4+ yr). The 16.5 degrees C and 25 degrees C lines are known to have
      diverged in fitness at 16.5 degrees C versus 25 degrees C and also in heat
      tolerance. We designed new experiments to explore further possible shifts in
      thermal sensitivity of these lines. The optimal temperature for walking speed of
      adults was positively related to selection temperature, but differences among
      lines in thermal sensitivity of walking speed were small. Performance breath was
      inversely related to selection temperature. Tolerance of adults to an acute heat
      shock was also positively related to selection temperature, but tolerance to a
      cold shock was not. Thus, fitness at moderately high temperatures is genetically
      coupled with tolerance of extreme high (but not of low) temperature. Knock-down
      temperature and walking speed at high temperature, however, were independent of
      selection temperature. In contrast to adults, eggs from different lines had
      similar heat and cold tolerance. Thus, long-term natural selection has led to
      divergence in thermal sensitivity of some (but not of all) traits and may have
      had more of an impact on adults than on eggs. Attempts to predict evolutionary
      states in nature are, however, complicated because of the observed genetic
      correlations and the simple selection scheme.

PMID- 9237301
TI  - Evidence for the involvement of the crustacean hyperglycemic hormone in the
      regulation of lipid metabolism.
AB  - Effects of the crustacean hyperglycemic hormone on total lipids in the hemolymph
      of Chasmagnathus granulata and on free fatty acids, phospholipids, and
      triglycerides in the hemolymph of Carcinus maenas, as well as on their release by
      Orconectes limosus hepatopancreas in vitro, were investigated. Eyestalk ablation
      led to a significant decrease of total lipids in the hemolymph of C. granulata
      and of free fatty acid levels in C. maenas. Crustacean hyperglycemic hormone
      injections completely reversed the effects of eyestalk extirpation in short-term
      experiments. Crustacean hyperglycemic hormone also caused significant elevations
      of hemolymph phospholipids and triglycerides in eyestalkless C. maenas. The
      release of free fatty acids and phospholipids from O. limosus hepatopancreas in
      vitro was significantly increased in the presence of crustacean hyperglycemic
      hormone. These results suggest a physiological role for crustacean hyperglycemic
      hormone in the control of lipid metabolism in crustaceans. This role may be
      similar to that of the adipokinetic hormone of insects.

PMID- 9237302
TI  - Age-related changes of plasma alkaline phosphatase and inorganic phosphorus, and
      late ossification of the cranial roof in the Spanish imperial eagle (Aquila
      adalberti C. L. Brehm, 1861).
AB  - Plasma alkaline phosphatase and inorganic phosphorus levels were determined for
      52 nestling Spanish imperial eagles from two wild populations and 22 captive
      adults and subadults (10 adults and 12 subadults). The exact age was known for
      all birds. Mean alkaline phosphatase and inorganic phosphorus were higher in
      chicks than in the captive adults and subadults. Sex differences were not
      observed, and nestlings from different populations showed similar values. No
      significant regression described the relationship between age and alkaline
      phosphatase or inorganic phosphorus throughout the nestling period. However,
      alkaline phosphatase and inorganic phosphorus decreased significantly throughout
      the subadult period, with age explaining 98.2% and 50.5% of the variation in
      alkaline phosphatase and inorganic phosphorus levels, respectively. Non-fully
      ossified zones were measured in frontal bones of another 12 subadult eagles that
      died at known ages. Ossification increased throughout the subadult period and was
      significantly correlated with expected levels of alkaline phosphatase or
      inorganic phosphorus (i.e., values predicted from the regression equations
      derived from the first analysis). Minimum alkaline phosphatase levels and full
      ossification of the cranial roof coincided with puberty onset. We conclude that,
      in subadult Spanish imperial eagles, decreasing alkaline phosphatase and
      inorganic phosphorus values are related to the ossification of frontal bones,
      although a contribution of other unknown processes of late ossification cannot be
      excluded, and alkaline phosphatase (but not inorganic phosphorus) may be a useful
      parameter for age-predicting purposes.

PMID- 9237303
TI  - Ion regulation in ion-poor acidic water by the blackskirt tetra (Gymnocorymbus
      ternetzi), a fish native to the Amazon River.
AB  - We examined the ionoregulatory capabilities of the blackskirt tetra
      (Gymnocorymbus ternetzi), which is native to ion-poor acidic waters of the Amazon
      River. Examination of Na+ uptake, which was only slightly sensitive to the uptake
      blocker amiloride, revealed several specializations for uptake in these waters.
      Kinetic analysis of Na+ uptake (at pH 6.5) revealed a high maximum rate of uptake
      and a low Michaelis-Menten constant, which allows the tetras to take up Na+ at
      high rates even at very low water levels. At pH 4.5, a pH where they experience
      sizable ion disturbances, they displayed several mechanisms to restore balance.
      Kinetic analysis at pH 4.5 revealed that the maximum uptake rate rose 67% while
      the Michaelis-Menten constant remained unchanged. Further tests showed that the
      upregulation of Na+ uptake occurred within 12 h in response to a doubling of Na+
      efflux. Despite these specializations of the Na+ uptake mechanism, blackskirt
      tetras were not especially tolerant of low pH. Upon exposure to pH 4.0, they
      experienced a massive loss of Na+ due to a fourfold increase of Na+ efflux
      (relative to pH 5.0) and an 80% inhibition of uptake. Measurement of Na+ efflux
      in waters with different Ca2+ levels and in the presence of LaCl, a strong Ca2+
      competitor, correlated the stimulation of Na+ efflux at low pH with a low
      branchial affinity for Ca2+. These tests indicate that blackskirt tetras possess
      abilities to resist the disruptive effects of moderately low pH but cannot
      survive in waters with a pH of 4.0 or less because of leaching of Ca2+ from
      branchial tight junctions, which stimulates ion losses.

PMID- 9237304
TI  - Temperature effects on the breeding distribution of grey seals (Halichoerus
      grypus).
AB  - The metabolic rates of six female grey seal (Halichoerus grypus) pups were
      measured during their postweaning fast at air temperatures between -15 degrees
      and 30 degrees C. The composite of their individual thermal neutral zones
      extended from a mean lower critical temperature of -7.1 degrees +/- 0.7 degree C
      to a mean upper critical temperature of 23.0 degrees +/- 0.4 degree C. Within the
      thermal neutral zone, mean standard metabolic rate of the fasting animals was
      1,265 +/- 82 kcal d-1, or about 1.1 times the value predicted for an adult animal
      of similar body mass (mean mass = 40.9 +/- 1.2 kg). For those grey seal
      populations that reproduce during winter months in the eastern and western
      Atlantic and in the Baltic Sea, the lower critical temperature of fasting pups
      corresponds closely with the coldest mean monthly air temperature at the northern
      end of their breeding ranges. This observation supports the hypothesis that cold
      ambient air temperatures limit the northern breeding distribution of grey seals,
      primarily through their thermoregulatory effects on small, fasting pups before
      they enter the water.

PMID- 9237306
TI  - Energy requirements of beavers (Castor canadensis) swimming underwater.
AB  - Energy requirements of beavers (Castor canadensis) swimming voluntarily
      underwater were investigated in Neumunster Zoo (Germany) in a covered, still
      water swim channel with oxygen and carbon dioxide respirometry. During the
      experiments, all activities of the beavers were monitored and recorded. While at
      rest within their thermoneutral zone on land (17 degrees C), beavers had a
      respiratory quotient of 0.95 and a resting metabolic rate of 1.58 W kg-1. When
      resting in water, energy requirements rose to 2.31 W kg-1. When swimming
      underwater in the channel, beavers preferred a mean speed of 0.64 m s-1, and
      their energy requirements rose to 2.64 W kg-1. Cost of transport, however, was
      minimal at 0.9 m s-1 and amounted to 0.36 J N-1 m-1. Although beavers must
      compromise form and function to operate on water and on land, their energy
      requirements while diving amount to only 1.65 times the resting metabolic rate
      and compare well with those of accomplished swimmers such as aquatic mammals and
      birds.

PMID- 9237305
TI  - Autonomic control of the pulmonary surfactant system and lung compliance in the
      lizard.
AB  - An increase in body temperature in the bearded dragon, Pogona vitticeps, is
      accompanied by an increase in the amount of pulmonary surfactant, a mixture of
      proteins and lipids, with the latter consisting predominantly of phospholipid and
      cholesterol. This increase may result from a temperature-induced change in
      autonomic input to the lungs, as perfusing the isolated lungs of P. vitticeps
      with either acetylcholine or adrenaline increases surfactant phospholipid
      release. However, whether acetylcholine acts via intrapulmonary sympathetic
      ganglia or directly on alveolar Type II cells is unknown. Moreover, the relative
      importance of circulating catecholamines and pulmonary sympathetic nerves on the
      control of the surfactant system is also obscure. Here, we describe the mechanism
      of the modulation of the surfactant system and the effect of this modulation on
      lung compliance. The role of acetylcholine was determined by perfusing isolated
      lungs with acetylcholine, acetylcholine and the ganglionic antagonist
      hexamethonium, or acetylcholine, hexamethonium, and the muscarinic antagonist
      atropine. Perfusing with acetylcholine significantly increased phospholipid
      release but did not affect cholesterol release. While histological examination of
      the lung revealed the presence of a large autonomic ganglion at the apex,
      blocking sympathetic ganglia with hexamethonium did not prevent the acetylcholine
      mediated increase in phospholipid. However, the increase was inhibited by
      blocking muscarinic receptors with atropine, which indicates that acetylcholine
      acts on muscarinic receptors to stimulate phospholipid release. By increasing
      pulmonary smooth muscle tone, acetylcholine decreased opening pressure and
      increased static inflation pressures. Plasma levels of noradrenaline and
      adrenaline increased with increasing temperature and were accompanied by a
      greater surfactant content in the lungs. While surfactant content was also higher
      in animals that exercised, plasma levels of adrenaline, noradrenaline, and
      dopamine were not elevated following exercise. Hence, surfactant release in the
      lizard lung may increase in response to an increase in plasma catecholamine
      levels. Acetylcholine, and hence the parasympathetic nervous system, may act to
      stimulate surfactant release but does not act via pulmonary sympathetic ganglia.
      We conclude that promoting surfactant secretion via an increase in circulating
      catecholamines may be inappropriate for a cold lizard with a requirement to
      conserve energy. As body temperature decreases, release of surfactant via
      nonadrenergic mechanisms, including cholinergic stimulation, may become
      increasingly important.

PMID- 9237307
TI  - Laboratory metabolism and evaporative water loss of the aardwolf, Proteles
      cristatus.
AB  - We examined oxygen consumption and total evaporative water loss of aardwolves
      (Proteles cristatus) at temperatures within and below their thermal neutral zone
      during both summer and winter. During summer (December), body masses of
      aardwolves averaged 8.1 +/- 0.7 kg (+/-1 standard deviation). Within their
      thermal neutral zone, oxygen consumption was 2,194 +/- 443 mL O2 h-1, or 1,058 kJ
      d-1. The relationship between oxygen consumption (VO2, mL O2 h-1) and ambient
      temperature (Ta, degree C) below the lower critical temperature was VO2 = 6,310
      178 (Ta). During winter (August), aardwolves had an average mass of 7.8 +/- 0.7
      kg and a basal metabolic rate of 1,844 +/- 224 mL O2 h-1, or 889 kJ d-1. Below
      the thermal neutral zone, VO2 = 4,308-116 (Ta). Basal metabolic rate and the
      slope of the line relating oxygen consumption to ambient temperature were both
      significantly higher in summer than in winter. Evaporative water loss increased
      with air temperature for both seasons but was higher in summer than winter. Wet
      thermal conductance was relatively constant below the thermal neutral zone, but
      was significantly higher in summer (0.022 +/- 0.001 mL O2 g-1 h-1 degree C-1)
      than in winter (0.015 +/- 0.001 mL O2 g-1 h-1 degree C-1).

PMID- 9237310
TI  - Now is the time for evidence based physiotherapy.

PMID- 9237308
TI  - On the thermal capacity of a bird's egg warmed by a brood patch.
AB  - Eggs of intermittently incubating birds are periodically rewarmed by a transient
      pulse of heat from the parent's brood patch. Estimating the energy cost of
      rewarming such an egg requires knowledge of the egg's thermal capacity, typically
      assumed to be the product of the egg's mass and its specific heat, designated
      here as the gravimetric thermal capacity. When chicken eggs are transiently
      warmed by an artificial brood patch, the energetic costs of the rewarming
      indicate that they have thermal capacities about one-third the gravimetric
      thermal capacity. In this article, I show that birds' eggs warmed locally by a
      brood patch have effective thermal capacities that differ substantially from the
      eggs' gravimetric thermal capacities, both in absolute magnitude and in response
      to varying the temporal properties of the transient pulse of heat. An effective
      thermal capacity exists because heat from a brood patch flows unevenly through an
      egg and because of thermal impedance effects on the unsteady component of heat
      flow into the egg. If these conditions in any way characterize the rewarming of
      eggs by intermittently incubating birds in nature, intermittent incubation may be
      considerably less costly in time and energy than has heretofore been assumed.

PMID- 9237309
TI  - Effects of endurance training in the leopard shark, Triakis semifasciata.
AB  - This study is the first to examine the effects of endurance training in an
      elasmobranch fish. Twenty-four leopard sharks (Triakis semifasciata) were divided
      randomly into three groups. Eight sharks were killed immediately, eight were
      forced to swim continuously for 6 wk against a current of 35 cm s-1 (60%-65% of
      maximal sustainable swimming speed), and eight were held for 6 wk in a tank
      without induced current. There were no changes due to training in maximal
      sustainable speed, oxygen consumption rates, percentage of the myotome composed
      of red and white muscle fibers, blood oxygen-carrying capacity, liver mass, liver
      lipid, glycogen, and protein concentrations, white muscle protein content, heart
      ventricle mass, or the specific activities of the enzymes citrate synthase,
      pyruvate kinase, and lactate dehydrogenase in the heart ventricle. In red
      myotomal muscle, citrate synthase activity increased 17% as a result of training,
      but there was no change in muscle fiber diameter. The greatest effects occurred
      in white myotomal muscle, in which a 34% increase in fiber diameter and a 36%
      increase in the activities of citrate synthase and lactate dehydrogenase occurred
      as a result of training. The conditioned fish also had significantly higher
      growth rates. The observed effects within the myotomal muscle may reflect the
      higher growth rates of the trained leopard sharks, or they may be a specific
      response to the increased energetic demands of the training activity, indicating
      characteristics that limit swimming performance in leopard sharks.

PMID- 9237311
TI  - To treat or not to treat--PVS or is he?

PMID- 9237312
TI  - Ethical issues in the management of persistent vegetative state.

PMID- 9237313
TI  - Redefining 'doing something': health professionals' views on their role in the
      care of stroke patients.
AB  - Stroke has traditionally been considered, both by lay people and by many people
      working within the health services, to be a tragic yet essentially uninteresting
      condition, possibly because of its associations with old age, chronicity and the
      widespread perception that very little can be done about it. This study explored
      health professionals' views about their role in caring for people with stroke,
      and about what they gained from and contributed to this work. Questionnaires were
      distributed to staff working on an elderly care unit, a general medical ward and
      a stroke unit. Nurses and physiotherapists were positive and reported that they
      had much to offer people with stroke, and many rewards to gain from their work.
      Occupational therapists reported that in theory they had much to contribute to
      people with stroke, but in practice lack of resources and staff shortages
      prevented them from fulfilling their potential. Speech therapists also complained
      of scarce resources, and of a lack of recognition of their specialty, but felt
      able to contribute to improving peoples' quality of life. Both psychologists
      reported that their work with people with stroke was satisfying and stimulating.
      However, with the exception of the consultant on the stroke unit, doctors
      reported feeling they had little to offer, and little to gain from working with
      people with stroke. Therapists on the elderly care unit, and speech therapists in
      all settings reported difficulties within the multidisciplinary team. Although
      each profession had different concerns and priorities, the majority seemed to
      have a positive approach to their work with people with stroke. Similarly, the
      majority reported that the best thing about their work was when people recovered,
      although professions defined recovery differently.

PMID- 9237314
TI  - The assessment of functional ability in patients with Parkinson's disease: the
      PLM-test and three clinical tests.
AB  - This study assesses functional ability of Parkinson's disease (PD) patients by
      means of an objective movement analysis (the PLM-test) and three clinical tests.
      The correlation between the tests was also studied. The main object of this study
      was to detect and measure relevant disabilities in Parkinson's disease to obtain
      a clinical test battery.

PMID- 9237316
TI  - Neurological physiotherapy--a personal view.

PMID- 9237315
TI  - Open versus arthroscopic subacromial decompression: analysis of one-year results.
AB  - The results of open subacromial decompression (OSD) were compared with
      arthroscopic subacromial decompression (ASD) after 1 year in 32 subjects (4
      bilateral), and the correlation between the two shoulder rating scales for
      impingement was documented. Patients were evaluated clinically on the modified
      University of California at Los Angeles (UCLA) shoulder rating scale, and
      Constant scale. Scapular position and rotation were evaluated as well as a
      rotation and abduction shoulder strength test using the Cybex II dynamometer. No
      parameters revealed significant differences between the groups, except for the
      UCLA score which indicated an advantage for the ASD group (p = 0.046). The OSD
      group scored 24.5 (5.45) on the UCLA scale and 73.8 (18.9) on the Constant scale,
      whereas the ASD group scored 28.3 (5.6) and 80.8 (16.4). To study the correlation
      between both scales, the Pearson correlation product-moment coefficient was
      calculated and a high correlation (r = 0.81) obtained. Less mobility was found in
      the operated arm for all parameters, with the exception of glenohumeral abduction
      in both groups and passive elevation in the OSD group. Only in the OSD group did
      the scapula in the operated extremity show more abduction of the inferior angle
      of the scapula. Weaker abduction strength in the operated side was found in the
      ASD group, whereas in the OSD group there was significantly less adduction and
      external rotation strength at 180 degrees/s en 240 degrees/s. We conclude that
      after one year the open group tends to catch up with the arthroscopic patients
      and that the main benefits after arthroscopic surgery as described in literature
      are more evident in the shorter period.

PMID- 9237317
TI  - Successful coping, adaptation and resilience in the elderly: an interpretation of
      epidemiologic data.
AB  - The elderly are often thought to suffer inevitable declines in functional
      abilities due to normal aging and concomitant diseases (acute and chronic). This
      view may be true for many aspects of physical health. However, an abundance of
      evidence suggests that mental health diverges from physical health in that
      Coping, Adaptation and Resilience (CAR) functions are surprisingly well-preserved
      throughout most of the life span. The normal "anatomy" and "physiology" of the
      CAR construct is described. It's robust relationship with the abnormalities of
      DSM-IV geriatric mental disorders is illustrated. Opportunities for new
      approaches to treatment are noted. These insights from the elderly are applicable
      to all age groups.

PMID- 9237318
TI  - Treatment of major depression in later life: a life cycle perspective.
AB  - The goal of this article is to provide a life-cycle perspective on the treatment
      of major depressive episodes in later life. Our studies have suggested that older
      patients appear to benefit as much, though perhaps more slowly, than mid-life
      patients from acute combined treatment (nortriptyline+interpersonal
      psychotherapy) of major depression. Given also the apparently higher relapse rate
      among the elderly, however, continuation treatment needs to be vigorous and
      closely monitored. The occurrence of severe life events prior to the index
      episode and the co-existence of an anxiety disorder both appear to prolong
      treatment response times, while chronic medical burden per se neither compromises
      response rates nor prolongs time to response. Self-rated perception of health
      improves with remission of depression in the elderly. As in mid-life patients,
      both antidepressant medication (nortriptyline) and interpersonal psychotherapy
      appear to possess chronic efficacy with respect to the prevention of recurrent
      episodes and prolongation of wellness. Finally, treatment of depression in the
      elderly results in improved quality of life, especially in domains of well being
      and coping. Particular challenges in the treatment of elderly patients are
      noncompliance and the prevention of suicide. The latter is closely linked to
      feelings of hopelessness, and these may be persistent in some patients.

PMID- 9237319
TI  - Geriatric psychosis.
AB  - This article reviews diagnostic and treatment issues which merit special
      consideration in the elderly psychotic patient. Psychoses are serious psychiatric
      disorders and can present in different forms in the elderly. The important ones
      include schizophrenia, psychosis in patients with dementia, psychosis in patients
      with depression and delusional disorder. Typical and atypical antipsychotic
      medications remain the treatment of choice for psychotic disorders but special
      considerations are warranted when prescribed to elderly patients. We have
      highlighted differences between younger and older adults in terms of clinical
      characteristics and treatment of psychotic disorders.

PMID- 9237321
TI  - Lessons from geriatric psychiatry in the long-term care setting.
AB  - Of all long-term care settings, the nursing home has served as the most
      productive laboratory for the study of the mental health problems of late life.
      Lessons from geriatric psychiatry research and practice in the nursing home have
      relevance to general psychiatry and to other health care settings, informing us
      about (a) psychiatric disorders in medically ill and disabled populations; (b)
      subsyndromes and subtypes of depression; (c) behavioral disturbances in patients
      with brain injury; (d) the effects of government regulation and education on
      mental health care; and (e) essential roles for psychiatrists in changing health
      care systems. Selected areas of knowledge based on geriatric psychiatry research
      and experience in long term care are reviewed in this paper, and their
      applications for the field of psychiatry in general are explored.

PMID- 9237320
TI  - The dementing disorders.
AB  - Dementing disorders are found most commonly in the elderly. However, the
      approaches derived from the diagnosis and management of these patients exemplify
      principles which can equally well be applied to the management of psychiatric
      disorders in younger patients. These principles include the process of syndromic
      diagnosis, the need for multi-dimensional assessment, the recognition of the
      interaction of biological and psycho-social factors in the etiology and treatment
      of psychiatric symptoms and the crucial role of the family in the management of
      patients with dementia. In this paper these principles are discussed.

PMID- 9237322
TI  - Toxicological risk assessment of worker exposure to pesticides: some general
      principles.

PMID- 9237323
TI  - Hazard assessment of germanium supplements.
AB  - Germanium-containing dietary supplements became popular in the 1970s in Japan and
      later in other countries, as elixirs for certain diseases (e.g., cancer and
      AIDS). Germanium is not an essential element. Its acute toxicity is low. However,
      at least 31 reported human cases linked prolonged intake of germanium products
      with renal failure and even death. Signs of kidney dysfunction, kidney tubular
      degeneration, and germanium accumulation were observed. Other adverse effects
      were anemia, muscle weakness, and peripheral neuropathy. Recovery of renal
      function is slow and incomplete even long after germanium intake was stopped. The
      total dose of ingested germanium (as dioxide, carboxyethyl germanium sesquioxide,
      germanium-lactate-citrate, or unspecified forms) varied from 15 to over 300 g;
      the exposure duration varied from 2 to 36 months. In laboratory animals, elevated
      germanium in tissues and impaired kidney and liver function were observed in a
      life-time drinking water (5 ppm germanium) study. Other toxicities associated
      with ingested germanium products in human cases were also demonstrated in animal
      studies with germanium dioxide and sometimes other germanium compounds. Based on
      the evidence of persistent renal toxicity associated with germanium dioxide, the
      lack of conclusive findings of differential nephrotoxicity of organic germanium
      compounds, and the possibility of contamination of the organic germanium products
      with inorganic germanium, it is clear that germanium products present a potential
      human health hazard.

PMID- 9237324
TI  - Environmental hazard assessment of pharmaceuticals.
AB  - The pharmaceuticals and pharmaceutical metabolites salicylic acid, paracetamol,
      clofibrinic acid, and methotrexate were examined with regard to their biological
      degradability and toxicity toward algae, Daphnia, fish embryos, luminescent
      bacteria, ciliates, and the fish cell line BF-2. The EC50 values calculated for
      the most sensitive organismic test (all except cell cultures) in each case were
      for salicylic acid, 37 mg/L (fish embryos); for paracetamol, 50 mg/L (Daphnia);
      for clofibrinic acid, 86 mg/L (fish embryos); and for methotrexate, 45 mg/L
      (ciliates). However, in the case of paracetamol, clofibrinic acid, and
      methotrexate, the fish cell line BF-2 reacted even more sensitively with EC50
      values of 19 mg/L (paracetamol), 14 mg/L (clofibrinic acid), and 3 mg/L
      (methotrexate). Salicylic acid and paracetamol proved to be easily degradable.
      The predicted exposure concentration calculated according to the procedure of the
      EU Draft Phase I for new pharmaceuticals (CEC III/5504/94, draft 4) was based on
      the total estimated quantity of these substances consumed and indicated that
      their entry into the environment is theoretically possible. These results show
      that (1) the four tested pharmaceuticals may be present in the environment, (2)
      the substances led to effects in at least one ecotoxicological test, and (3) the
      most sensitive reactions were observed for a nonstandard test which incorporates
      relevant end points for the respective pharmaceuticals. This demonstrates that a
      limitation to the standard tests (algae, Daphnia, and fish) would have
      underestimated the toxicity of paracetamol, clofibrinic acid, and methotrexate.
      In addition to improved exposure estimates, the EU guideline should therefore
      contain a test strategy adapted to their modes of action, which permits the
      definite identification of pharmaceuticals with high ecotoxic potential, and
      consequently the appropriate provisions.

PMID- 9237325
TI  - Activity of raloxifene in immature and ovariectomized rat uterotrophic assays.
AB  - Raloxifene is generally regarded as a tissue-selective estrogen agonist, being
      capable of selectively counter-acting both the loss of bone density and the
      increase in serum cholesterol that occur in rats following ovariectomy, without
      the induction of a trophic effect on the rat uterus. An implication of this
      activity profile is that reliance cannot be placed on the rat uterotrophic assay
      for the detection and assessment of xenobiotic estrogens. Within that context the
      estrogenic activity of raloxifene has been reevaluated in immature and
      ovariectomized rat uterotrophic assays. Four separate experiments were conducted.
      In the first two a reproducible increase (1.7-fold) was observed in the uterus
      wet weights of immature rats administered three daily doses of raloxifene. The
      maximum uterotrophic response observed over the dose range 0.01-2 mg/kg was for
      0.1 mg/kg raloxifene. Further experiments utilized three daily doses of 0.1 mg/kg
      raloxifene. In the third experiment the uterotrophic response elicited by
      raloxifene in immature rats was abolished by coadministration of the estrogen
      receptor blocking agent Faslodex (ICI 182,780). This confirmed the direct
      involvement of estrogen receptors in the uterotrophic response elicited by
      raloxifene. Two further indications of the estrogenicity of raloxifene were
      obtained in this experiment. First, dry uterus weights were also shown to be
      increased by raloxifene administration, thereby eliminating water retention as
      the sole cause of the observed increases in uterus weights. Second, the height of
      the surface epithelium was increased by 1.7-fold in the raloxifene-treated
      animals, an effect that was accompanied by increases in mitotic activity and
      glandular formation in the stromal endometrium. The endometrial epithelium of the
      treated rats also showed evidence of vacuolation and, occasionally, the presence
      of degenerating cells. Raloxifene did not, however, cause premature vaginal
      opening in immature rats, unlike estradiol. In the fourth experiment the
      uterotrophic activity of raloxifene was confirmed in ovariectomized rats,
      although the response was less (1.2-fold) than in immature rats. In contrast to
      the effects seen for the positive control agent estradiol, the uterotrophic
      responses observed for raloxifene in ovariectomized animals were not accompanied
      by cornification of the vaginal epithelium. Premature vaginal opening and vaginal
      cornification may be less sensitive markers of estrogenic activity than the
      uterotrophic response. These collected observations confirm that raloxifene
      exerts a genuine trophic effect on the rat uterus, and as a consequence, the
      uterotrophic assay can be relied upon to detect estrogens with only a marginal
      effect on the uterus.

PMID- 9237326
TI  - Qualitative industrial hygiene product life cycle analysis applied to refractory
      ceramic fiber (RCF) consumer product applications.

PMID- 9237327
TI  - Evaluation of alternative methods for establishing safe levels of occupational
      exposure to vinyl halides.
AB  - The facts that reduction of occupational vinyl chloride exposures to levels
      within or below the 0.5-5 ppm range has so far been successful in eliminating
      vinyl chloride-induced liver angiosarcoma and that humans appear to be less
      sensitive to the carcinogenic effect of vinyl chloride than rats offered an
      opportunity to verify or dispute risk assessment extrapolation models used, and
      proposed, by the U.S. EPA. Safe occupational vinyl chloride exposures were
      defined as levels associated with an incidence of one angiosarcoma in 100,000
      exposed workers, determined from rat bioassay data using default no-threshold
      (linearized multistage model and benchmark dose approach with linear
      extrapolation) and threshold (NOEL/LOEL and benchmark dose uncertainty factor
      approaches) models, and then compared against the likely protective range of 0.5
      5 ppm. Safe levels derived using either no-threshold model are equivalent and are
      two to three orders of magnitude below the 0.5-5 ppm range. Safe levels derived
      using either threshold model, when applying uncertainty factors which reflect
      equal or less sensitivity in humans compared to rats, fall within the 0.5-5 ppm
      range. Similar results were obtained for vinyl bromide and vinyl fluoride. These
      results undermine the U.S. EPA default assumption of no-threshold for vinyl
      halides as well as for other DNA-reactive carcinogens while simultaneously
      supporting the notion that a practical threshold exists. They further suggest
      that when threshold models are appropriate, the default assumption of greater
      sensitivity in humans compared to rats should be carefully evaluated.

PMID- 9237328
TI  - Atmospheric and potable water exposures to methyl tert-butyl ether (MTBE).
AB  - This paper presents information on the ways in which people can be exposed to
      methyl tert-butyl ether (MTBE) via air and water and on the distribution of doses
      that can result from those exposures. Data on concentrations of MTBE in air were
      complied for 15 different occupational, commuting, or residential exposure
      categories, and concentrations in potable water were complied from five states in
      the MTBE-using areas of the United States. Based on these concentrations and
      characteristics of the exposed populations, average daily and lifetime average
      doses were estimated. Both the concentration data and several of the population
      characteristics were estimated as distributions rather than as point values so
      that the numbers of people exposed at various levels could be estimated.
      Arithmetic mean occupational doses via air were in the range of 0.1 to 1.0 mg/kg
      day, while doses from residential exposures, commuting, and refueling were in the
      range of 0.0004 to 0.006 mg/kg-day. Lifetime doses for workers were in the range
      0.01 to 0.1 mg/kg-day. The cumulative dose distribution for the entire population
      of the MTBE-using regions of the United States was estimated by combining the
      distributions of doses and the numbers of people in each exposure category. In
      the MTBE-using areas, arithmetic mean doses via air were estimated to be 0.0053
      and 0.00185 mg/kg-day for the chronic and lifetime cases, respectively.
      Approximately 98.5% of the population living in MTBE-using regions uses water
      with concentrations affected only by atmospheric deposition, if at all, and too
      low to be detected with current methods (< 2 micrograms/liter). The remaining
      population uses water with an estimated geometric mean concentration of 0.36
      microgram/liter, an arithmetic mean concentration of 49 micrograms/l, and a 95th
      percentile concentration of 64 micrograms/liter. Doses via ingestion, inhalation,
      and dermal absorption were included. The estimated arithmetic mean dose for the
      population exposed via water was 1.4 x 10(-3) mg/kg-day.

PMID- 9237329
TI  - Estimation of the interindividual variability in the one-compartment
      pharmacokinetic model for methylmercury: implications for the derivation of a
      reference dose.
AB  - A critical step in the U.S. EPA's derivation of an Reference Dose (RfD) for
      methylmercury is conversion of the maternal hair Hg concentration of 11 ppm to
      average daily intake using the one-compartment pharmacokinetic model. A default
      uncertainty factor (UF) adjustment of 3 for interindividual variability was then
      applied to this conversion. A probabilistic (Monte Carlo) analysis is presented
      estimating the interindividual variability inherent in this dose conversion for
      women 18-40 years old based on data in the scientific literature. The dose of 1.1
      micrograms/kg/day, calculated by the U.S. EPA to correspond to 11 ppm Hg in hair,
      is estimated in this analysis to be larger than 94-99% of corresponding doses.
      The application of a UF of 3 to this U.S. EPA value gives a dose which is
      estimated to be larger than 28-73% of corresponding doses. This analysis suggests
      that if the dose conversion in the RfD is intended to be inclusive of 95-99% of
      women 18-40, the daily intake should be set at 0.1-0.3 microgram/kg/day. The RfD
      of 0.03-0.1 microgram/kg/day, derived from this dose by the U.S. EPA's
      application of an additional UF of 3 for additional toxicologic concerns, is
      somewhat smaller than the current RfD of 0.1 microgram/kg/day.

PMID- 9237330
TI  - Summary of the report "toxicology-based recommended exposure limits".

PMID- 9237331
TI  - Dose-response assessment strategies for endocrine-active compounds.
AB  - Hazard identification provides evidence for the potential of compounds to cause
      effects in exposed people. Dose-response assessments define the range of exposure
      conditions associated with minimal risks of adverse effects. With endocrine
      active compounds (EACs), the vast majority of resources are presently being
      applied to hazard identification. In the past, dose-response assessments have
      been based on empirical analysis of these relationships. The empirical
      underpinnings of these models do not permit conclusions about the low-dose and
      interspecies extrapolation of the animal study results. Biologically based dose
      response assessments relying on knowledge of mode-of-action (pharmacodynamics)
      and dosimetry (pharmacokinetics) offer promise to develop broadly applicable
      strategies for quantitative dose-response assessments with these EACs. These
      approaches would focus on normal physiological endocrine signaling processes in
      the body, their associated control mechanisms, and the interaction among
      different internal signaling pathways. A critical element of signaling is
      regulation of the concentration of the signaling compound, e.g., steroid sex
      hormone. Exogenous compounds that act as signals but evade the normal homeostatic
      control of signaling compound concentrations represent one class of EACs. Other
      molecular components of these signaling systems include receptors, second
      messengers, and DNA-accessory/transcriptional protein complexes; EACs may
      interfere with the functions of any of these components. The challenge facing the
      toxicology and risk assessment professions is to base regulatory strategies on
      the interaction of these EACs with the fundamental control mechanisms which
      regulate responses throughout the body and to determine the extent to which these
      interactions create specific dose-response behaviors in the living animals.

PMID- 9237332
TI  - Data on arsenic and cadmium contents of some common mushrooms.
AB  - The arsenic and cadmium contents of 88 samples of mushrooms were determined. The
      majority of samples have a very low (practically zero) arsenic level; however,
      significant accumulations were found in the Agaricus species and in Macrolepiota
      rhacodes (which is related to the Agaricaceae family) and in three
      Tricholomataceae species (Flammulina velutipes, Lepista nebularis and Clitocybe,
      inversa). The average cadmium content of all samples was 4.91 ppm (0.28-86 ppm)
      on a dry weight basis. The highest concentration (34.9 ppm) was found to be
      characteristic of genus Agaricus. The accumulation potential of genus Russula is
      lower, and it appears that this content is more characteristic in three sections
      (Ingratea, Heterophyllae and Xerampelinae), whereas the others have a low
      (normal) cadmium level. These data confirm that the accumulation ability is
      genetically coded, thus, only certain taxonomical groups of fungi play a
      toxicological role. Our data offer new information about the concentration of two
      toxic elements of particular mushroom species as well as in other taxonomic
      groups. These data are of great importance in view of toxicology, food chemistry
      and, partly, environmental protection.

PMID- 9237333
TI  - Glycerol-induced augmentation of sensitivity to endotoxin in rats.
AB  - Combined sepsis and rhabdomyolysis result in a mortality rate much higher than
      that caused by each process alone. An analogous rat model is obtained by
      simultaneous i.p. administration of a nonlethal dose of lipopolysaccharide (LPS
      0.025 mg/100 g) and a nonlethal i.m. injection of glycerol (1 ml/100 g). The aim
      of this study was to determine the factors contributing to the high mortality
      rate in this rat model. The factors examined include: Dehydration, plasma volume
      expansion, 'immunization' to glycerol, induction of LPS tolerance and the effect
      of free radicals formed in this model. Neither dehydration nor volume expansion
      affected mortality. 'Immunization' with glycerol was also not effective. In
      contradistinction, tolerance to LPS achieved by a daily injection with gradual
      increasing doses of LPS (from 0.05 mg/100 g to 1 mg/100 g) for 6 days reduced the
      mortality rate by 60% (P < 0.001). Moreover, decreasing free radical activity
      using the natural antioxidant (NAO) (5 mg/100 g) reduced mortality rates by 50%.
      A different antioxidant, dimethylthiourea (DMTU) (50 mg/100 g) failed to reduce
      mortality rates. This study suggests that the synergism between glycerol and LPS
      is apparently due to an increase in the rats' sensitivity to endotoxin following
      glycerol injection. However, endotoxin apparently does not enhance sensitivity to
      glycerol in the rat. The new antioxidant NAO significantly reduced the high
      mortality rate.

PMID- 9237334
TI  - Pseudomonas aeruginosa cytotoxin as a pathogenicity factor in a systemic
      infection of leukopenic mice.
AB  - The effect of Pseudomonas aeruginosa cytotoxin was assessed in leukopenic outbred
      Swiss male mice (20 g) using a high cytotoxin-producing strain (PA158) and its
      cytotoxin-deficient isogenic mutant (PA114F5) generated by Tn7::Tn5 transposon
      mutagenesis of PA158. Leukopenia was induced by intraperitoneal (i.p.)
      administration of cyclophosphamide (150 micrograms/g). Anesthetized mice were
      infected via a 4 mm incision on the shaved back with 300 CFU/mouse (9 LD50;
      expected death rate 85%). Precleared mouse cytotoxin-specific heat inactivated
      rabbit polyclonal antibody (RPA) was administered i.p. (0.2 ml) 24 hr before
      challenge. Controls received i.p. normal rabbit serum, RPA, cyclophosphamide
      alone, or a sham procedure. Challenge with the high cytotoxin-producing strain
      PA158 caused earlier and a significantly greater mortality than that observed
      with a cytotoxin-deficient strain PA114F5 (P < 0.01). Cytotoxin-specific
      polyclonal antibody was protective. Pretreatment with antibody decreased the
      mortality rate following challenge with PA158 from 88.9% to 27.8% (P < 0.01).
      Pretreatment with antibody decreased the mortality rate following challenge with
      PA114F5 from 27.8% to 5.6% (P < 0.05). These results demonstrate that P.
      aeruginosa cytotoxin contributes to the pathogenicity of the organism and that
      cytotoxin antibody is protective in a systemic P. aeruginosa infection in
      leukopenic mice.

PMID- 9237335
TI  - Anticholinesterases as antidotes to envenomation of rats by the death adder
      (Acanthophis antarcticus).
AB  - The purpose of this study was to find an antidote against death adder
      envenomation that can be used in cases of emergency, when antivenoms are not
      readily available (Papua New Guinea and the Australian outback). Such an antidote
      should allow bite victims to survive until established treatment is possible.
      Death adder venom is thought to act postsynaptically at the neuromuscular
      junction to reduce responses to acetylcholine. This causes severe flaccid
      paralysis and finally death, which is usually a consequence of respiratory
      failure. Albino Wistar rats were injected with a lethal dose of crude death adder
      venom. At the onset of severe envenomation symptoms, anticholinesterases
      (neostigmine and edrophonium) in conjunction with atropine sulfate were
      administered. At the minimum lethal dose (0.15 mg/kg) all animals survived as a
      result of the anticholinesterase treatment. The expected survival time of animals
      subjected to higher venom doses was significantly extended. These results
      indicate that death adder bite victims may gain valuable time, if
      anticholinesterases can be administered during the initial critical stage of
      envenomation.

PMID- 9237336
TI  - The dynamics of local tissue damage induced by Bothrops asper snake venom and
      myotoxin II on the mouse cremaster muscle: an intravital and electron microscopic
      study.
AB  - The acute tissue damaging effects of Bothrops asper snake venom and a myotoxic
      Lys-49 phospholipase A2 (myotoxin II) on the mouse cremaster muscle were studied
      by intravital and electron microscopy. Both venom and myotoxin induced local
      contractions of the muscle fibres within 10-60 sec after exposure, which
      disappeared after 1-2 min. This observation is consistent with the hypothesis
      that Bothrops myotoxins act initially at the sarcolemma by affecting its
      permeability and allowing an influx of calcium. The venom also induced an early
      but transient vasoconstriction of arterioles. The development of edema was
      monitored using i.v. FITC-dextran as a marker. Plasma leakage started after about
      2 min of exposure to venom or myotoxin, was extensive by 4-5 min, and originated
      from small venules and their adjoining capillary segments. The venom induced
      formation of thrombi and emboli in venules, but not in arterioles. Haemorrhage
      appeared after 4-6 min of exposure, the bleedings always originating from
      capillaries and small venules. The microbleedings were explosive, appearing as
      rapid bursts of erythrocytes into the extravascular space, and suggesting a per
      rhexis type of haemorrhage. This was confirmed by electron microscopy evaluation
      of the same microvessels observed intravitally, which showed erythrocyte
      extravasation through gaps in damaged endothelial cells. Other phenomena in the
      microcirculation included blood-flow disturbances, crenation and sphering of
      erythrocytes, and stasis with dense packing of cells in capillary networks.
      Muscle necrosis, caused by either venom or myotoxin, started 3-4 min after
      application. The first sign of damage in the fibres was the development of a
      narrow, transverse band with local loss of striation. This was followed by slow
      retraction of myofibrils until there was a complete transverse rupture of the
      fibre. This process was often repeated along the same fibre, leaving a row of
      fragments separated by spaces apparently devoid of myofibrillar material. The
      results confirm the rapid tissue damaging effects of B. asper venom, implying
      that potentially useful blocking agents must be administered early and have the
      ability to diffuse rapidly into the tissues.

PMID- 9237337
TI  - Effect of cooking on the concentration of toxins associated with paralytic
      shellfish poison in lobster hepatopancreas.
AB  - The hepatopancreases from lobsters (Homarus americanus) obtained from two
      locations in eastern Canada (Gaspe and Bay of Fundy) were analysed for paralytic
      shellfish poisons (PSP) before and after the shellfish were cooked by boiling or
      steaming. Forty-five lobsters from each location were divided into three groups
      of 15. Two of the groups were boiled or steamed while the third was uncooked for
      comparison purposes. The hepatopancreases of all lobsters were individually
      analysed for total PSP toxicity using the standard mouse bioassay procedure.
      Individual toxins were determined in each sample using a high-performance liquid
      chromatographic procedure employing pre-chromatographic oxidation of the toxins
      to form fluorescent derivatives. The results demonstrated that boiling or
      steaming reduced total toxicity (measured as saxitoxin equivalents per
      hepatopancreas) by approximately 65% compared to values obtained from raw
      lobsters. Of the individual toxins studied, saxitoxin decreased by about 60% with
      both the cooking treatments while gonyautoxins 2 and 3 (combined) decreased by
      almost 100% in the Gaspe samples and by about 90% in the Fundy samples with the
      same cooking treatments. Trace amounts of saxitoxin or gonyautoxins 2 and 3 were
      detected in some samples of tail or claw meat before or after cooking. In vitro
      boiling of raw hepatopancreas for up to 30 min led to no change in total or
      individual PSP concentration, indicating that the toxins in cooked lobster are
      not removed through chemical decomposition but are leached out during the loss of
      water.

PMID- 9237338
TI  - The humoral and cellular immune response to a lipid attenuated pore-forming toxin
      from the sea anemone Actinia equina L.
AB  - The immunogenicity of a pore-forming polypeptide, equinatoxin II, from the sea
      anemone Actinia equina was studied after attenuation of the toxin's lethal and
      cytolytic activity by autologous polar lipids. In BALB/c mice, the lipid
      inactivated toxin was used to raise specific antibodies and cellular immunity,
      resulting in in vivo protection. In vitro, haemolytic activity could be
      diminished by both normal and immune serum, the latter being more efficient.
      Purified specific IgG1 and IgG2 did not or only poorly neutralized the haemolytic
      activity, therefore implying the marked role of serum lipoproteins in the toxin
      attenuation. In response at the cellular level, equinatoxin II activated specific
      splenocytes. Increased concanavalin A stimulation of specific splenocytes was
      observed in the absence of antigen.

PMID- 9237339
TI  - Isolation of cylindrospermopsin from a cyanobacterium Umezakia natans and its
      screening method.
AB  - In 1987 a cyanobacterium (blue-green alga) Umezakia natans was isolated from Lake
      Mikata, Fukui, Japan, as a new member of the family of Stigonemataceae. The crude
      extract of U. natans showed hepatotoxicity to mice, from which a toxic compound
      was isolated. The toxin was identical in all respects to a recently reported
      hepatotoxin, cylindrospermopsin, isolated from an Australian tropical
      cyanobacterium Cylindrospermopsis raciborskii. Because cylindrospermopsin causes
      fatty liver and central necroses in mice and is suspected of being an agent
      causing human hepatoenteritis, its monitoring in drinking water supplies has been
      required. So a rapid screening method including four steps, extraction, clean-up,
      separation, and determination, has been proposed for cylindrospermopsin. A
      combination of a clean-up using HP-20 and C18-cartridge, and HPLC with photodiode
      array detector made it possible to establish a screening method for the toxin.
      The established method was applied to five samples and cylindrospermopsin was
      traced in one of them.

PMID- 9237340
TI  - Effects of the venom of the theridiid spider, Steatoda capensis Hann, on
      autonomic transmission in rat isolated atria and caudal artery.
AB  - The possibility of alpha-latrotoxin-like activity in the crude venom gland
      extract (VGE) of a related Theridiid spider, Steatoda capensis Hann, was
      investigated. The VGE from female S. capensis Hann spiders produced
      vasoconstriction in isolated segments of rat caudal artery but was without effect
      in artery segments obtained from rats that had been pretreated with reserpine
      (2.5 mg/kg) 24 hr prior to experimentation, indicating that the vasoconstriction
      was due to the release of noradrenaline from periarterial sympathetic nerves.
      Steatoda capensis Hann VGE also increased the rate of beating of rat isolated
      atrial preparations. The positive chronotropic action of the VGE was partly due
      to the release of noradrenaline from atrial sympathetic nerves since it was
      reduced by the beta-adrenoceptor antagonist propranolol, and smaller increases in
      rate were observed in atria taken from rats pretreated with reserpine. The
      positive chronotropic effect of the VGE was enhanced by atropine, suggesting that
      the VGE also releases acetylcholine from atrial parasympathetic nerves. The VGE
      evoked release of radioactivity from rat atria in which the transmitter stores of
      the atrial intramural noradrenergic nerves had been labelled with
      [3H]noradrenaline. There appeared to be two components of the release, one
      involving omega-conotoxin GVIA-sensitive Ca2+ channels, and the other independent
      of extracellular Ca2+.

PMID- 9237341
TI  - Antithrombin III and antivenom reversal of coagulopathy in rats envenomated with
      Malayan pit viper venom.
AB  - The therapeutic effects of antithrombin III (AT-III) and unrefined equine
      antivenom in the treatment of coagulopathy induced by Malayan pit viper
      (Calloselasma rhodostoma) venom were assessed in 42 adult Wistar rats. Following
      intramuscular venom injection (2 micrograms/g body weight), serial blood samples
      were taken from the femoral vein for measurement of whole blood clotting time and
      AT-III activity. There was progressive depletion of AT-III and blood ceased to
      clot a mean (S.E.) of 164 (8.3) min after venom injection. Coagulopathy was
      reversed by a high dose antivenom (10 micrograms/g) or a lower dose of antivenom
      (5 micrograms/g) in combination with AT-III (> or = 0.1 U/g; P < 0.01) but not 5
      micrograms/g antivenom or AT-III alone. Following successful treatment, the mean
      plasma AT-III activity remained above 90%. In this animal model, systemic
      envenomation by the Malayan pit viper causes uncoagulable blood associated with
      AT-III consumption. The dose of antivenom required to reverse this coagulopathy
      can be reduced by half by the addition of AT-III sufficient to maintain blood
      concentrations within the normal range.

PMID- 9237342
TI  - Inhibition of hormone-stimulated inositol phosphate production and disruption of
      cytoskeletal structure. Effects of okadaic acid, microcystin, chlorpromazine, W7
      and nystatin.
AB  - Inhibition of protein phosphatases 2A and 1 by okadaic acid and microcystin leads
      to cytoskeletal disruption and formation of plasma membrane blebs (blebbing) in
      hepatocytes. This phenomenon is associated to a marked inhibition of receptor
      mediated and G-protein-mediated phosphoinositide turnover in rat hepatocytes.
      Other cytoskeletal-disrupting drugs such as chlorpromazine, W7 and nystatin mimic
      the effect of these protein phosphatase inhibitors on phosphoinositide metabolism
      and blebbing. Our data suggest that the coupling between G-protein and
      phospholipase C might be altered by cytoskeletal disruption.

PMID- 9237343
TI  - Antigenic cross-reactivity of venoms from medically important Loxosceles
      (Araneae) species in Brazil.
AB  - Antigenic cross-reactivity between the components of venoms from three spiders of
      the genus Loxosceles, L. gaucho, L. laeta and L. intermedia, was studied. Species
      specific antisera were prepared by immunization of rabbits with each venom. Anti
      L. gaucho horse hyperimmune serum provided by the Butantan Institute for
      treatment of accidents with these spiders was also used. Separation by SDS-PAGE
      showed the existence of many common components in the three antigens. No
      individual antigen was observed. Analysis of the antisera by ELISA and Western
      blotting showed cross-reactivity as well as several common bands between the
      three venoms. The horse anti-L. gaucho venom serum recognized many common
      proteins when antigens of the other two species were used. Antigens in the range
      of 33,000-35,000 mol. wt showed most cross-reactivity. Both horse and rabbit anti
      venom sera contained antibodies able to neutralize the lethal and dermonecrotic
      activities of the venom of the three species studied.

PMID- 9237344
TI  - Inhibitory effects of Microcystis aeruginosa toxin on ion pumps of the gill of
      freshwater fish.
AB  - A microsomal fraction enriched in ion pump enzymes was isolated from the gill of
      the carp (Cyprinus carpio Linneo). Mg(2+)-dependent (Na+ + K+), Na+, HCO3- and
      Ca(2+)-stimulated ATPase activities were studied following treatment with
      microcystin-LR-like toxin, the major toxic component isolated from Microcystis
      aeruginosa culture. These enzyme activities were inhibited in a dose-dependent
      manner. The maximum inhibition of each enzyme, induced with nM concentration of
      the toxin, was similar to that produced by inhibitors specific for each ATPase
      activity. The Mg(2+)-ATPase activity and non-specific hydrolysis of ATP were
      unaffected. These results strongly suggest that the massive fish death during M.
      aeruginosa blooms may result from the loss of ion homeostatic processes produced
      by the inhibitory action of microcystin on the ion pumps of gill chloride cells.

PMID- 9237345
TI  - Multivalent binding of toxin A from Clostridium difficile to carbohydrate
      receptors.
AB  - A specific monoclonal antibody against toxin A from Clostridium difficile was
      generated that did not show thermolabile binding. Nonspecific murine monoclonal
      antibodies bound toxin A at 4 degrees C, but less effectively at 37 degrees C.
      Nonspecific human monoclonal antibodies did not bind to toxin A at 4 degrees C.
      Cytotoxic properties of purified toxin A were not inhibited by Bandeiraea
      simplicifolia lectin. This points to a carbohydrate moiety on the cell surface
      and a multivalent nonspecific carbohydrate binding ligand on toxin A.

PMID- 9237347
TI  - Bibliography of toxinology.

PMID- 9237346
TI  - Isolation and identification of 12 microcystins from four strains and two bloom
      samples of Microcystis spp.: structure of a new hepatotoxin.
AB  - Sixteen microcystins, cyclic heptapeptide hepatotoxins, were isolated and
      purified by high performance liquid chromatography (HPLC) and thin layer
      chromatography (TLC) from four hepatotoxic strains and two Microcystis spp. bloom
      samples originating from five different lakes in Finland. The structures of a new
      [Dha7]MCYST-FR and 11 known microcystins MCYST-LR, [D-Asp3]MCYST-LR, [Dha7]MCYST
      LR, [D-Asp3, Dha7] MCYST-LR, MCYST-RR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, [D
      Asp3,Dha7]MCYST-RR, [L-Ser7]MCYST-RR, MCYST-YR and [Dha7] MCYST-YR were assigned
      based on amino acid analysis, fast atom bombardment mass spectrometry (FABMS) and
      tandem FABMS. Four other new compounds allowed only determination of their
      molecular formulas and amino acid components because of inadequate amounts
      obtained. [Dha7]MCYST-RR was found most frequently in these samples as the main
      toxin.

PMID- 9237348
TI  - Characterization of membrane-bound and membrane anchor-less forms of
      hemagglutinin glycoprotein of Rinderpest virus expressed by baculovirus
      recombinants.
AB  - The Rinderpest virus (RPV) hemagglutinin (H) is a class 2 glycoprotein by means
      of which the virus attaches to the host cell receptor. A full length cDNA coding
      for H protein was used to construct a recombinant baculovirus expressing the H
      protein, recH(M), on the surface of insect cells. The small N terminal
      cytoplasmic domain was deleted and the transmembrane domain which extends from
      amino acids 35 to 59 was replaced with a signal peptide derived from the
      ecdysteroid UDP glycosyl transferase (egt) gene of the baculovirus, AcNPV. The
      protein recH(sec) expressed by the recombinant baculovirus carrying this
      engineered gene was secreted into the medium. Both forms of recombinant H protein
      retained reactivity with conformation-dependent monoclonal antibodies. The
      recH(M) was recognized by antibodies made in cattle either as the result of
      vaccination or natural infection. The soluble form of H is a valuable tool for
      studying the structure and function of the RPV H glycoprotein.

PMID- 9237349
TI  - Identification and characterization of the feline herpesvirus type 1 glycoprotein
      C gene.
AB  - The feline herpesvirus type 1 (FHV-1) gene encoding glycoprotein C (gC) has been
      sequenced and identified based on its genomic location and comparative analysis
      to other alphaherpesvirus gCs, and the expressed gC protein was also identified
      by using specific monoclonal antibodies. The FHV-1 gC gene was located within a
      7.0 kbp EcoRI fragment, and was 1602 bp in length. The amino acid sequence
      deduced from the nucleotide sequence was predicted to encode a membrane
      glycoprotein containing a characteristic N-terminal hydrophobic signal sequence,
      nine potential N-linked glycosylation sites, and C-terminal transmembrane and
      cytoplasmic domains. The FHV-1 gC was expressed in COS-7 cells. When
      flowcytometric analysis was carried out, the gC expressed in COS-7 cells reacted
      with a panel of monoclonal antibodies against gp113: By immunoprecipitation
      analysis, the gC expressed in COS-7 cells possessed molecular masses of 125-150
      kilodalton, and was similar in size to that in FHV-1-infected CRFK cells.

PMID- 9237351
TI  - Computer simulations to identify in polyproteins of FMDV OK1 and A12 strains
      putative nonapeptides with amino acid motifs for binding to BoLA class I A11 and
      A20 haplotype molecules.
AB  - The computer program "Findpatterns" was used to search FMDV- (OK1 and A12
      strains) coded structural and nonstructural proteins for the availability of
      putative proteasome-generated nonapeptides with motifs reported for BoLA class I
      A11 and A20 haplotypes. These BoLA class I A11 and A20 nonapeptide motifs are
      identical to motifs of nonapeptides that interact with the peptide binding
      grooves of HLA class I B35 and B27 haplotypes, respectively. The computer
      findpattern program was used to analyze the FMDV-coded polyproteins for
      proteolytically cleavable nonapeptides with motifs for binding to the peptide
      binding grooves of BoLA class I A11 or 20 haplotypes. The computer simulations
      revealed that FMDV-infected cells (keratinocytes and antigen presenting cells.
      e.g., dendritic Langerhans cells in bovines) may be able to present viral
      nonapeptides to CD8+ cytolytic T cells (CTLs) in a BoLA-restricted manner. The
      role of the cellular arm of the immune response in the protection of bovines
      against FMDV is not known. Thus, the present computer analysis may encourage
      further experiments to develop a new generation of FMDV nonapeptide vaccines to
      stimulate the anti-FMDV cytolytic T cell response in bovine so this would
      complement the humoral immune response achieved by immunization with the
      inactivated virus vaccine.

PMID- 9237352
TI  - Complete sequence and transposon mutagenesis of the BamHI J fragment of Cydia
      pomonella granulosis virus.
AB  - The BamHI J fragment of Cydia pomonella granulosis virus was subcloned and
      subjected to transposon mutagenesis in Escherichia coli using a Tn3 derivative.
      After screening by restriction endonuclease digestion and polymerase chain
      reaction (PCR), 44 clones were selected representing insertions every 100 to 300
      bp. The complete sequence was compiled and the transposon insertion sites mapped
      precisely by sequencing. Analysis of the sequence revealed the presence of 7
      potential open reading frames (ORFs). The BamHI J fragment was already known to
      encode IAP and OPDV-E6. Three other ORFs encode products similar to known
      proteins, viz. an Autographa californica nuclear polyhedrosis virus 8.6 kDa
      protein, a Lymantria dispar nuclear polyhedrosis virus 34 kDa protein, and
      vertebrate reovirus omega-1 proteins. The ORF with similarity to omega-1 is also
      similar to baculovirus p10 proteins. In both cases, the similarity occurs in
      regions likely to form a coiled-coil structure.

PMID- 9237350
TI  - The use of bovine MHC class I allele-specific peptide motifs and proteolytic
      cleavage specificities for the prediction of potential cytotoxic T lymphocyte
      epitopes of bovine viral diarrhea virus.
AB  - Cell mediated immunity (CMI) is crucial for the defense against viruses.
      Cytotoxic T lymphocytes (CTLs) play a major role in CMI. They recognize
      endogenous antigenic peptides presented by antigen presenting cells in
      association with the major histocompatibility complex (MHC) class I molecules.
      The elucidation of the sequence of CTL epitopes of viruses should help in
      designing better vaccines. In this study, we have identified candidate epitopes
      restricted by five bovine MHC class I molecules that are potentially available
      for presentation to CTLs. The candidate peptide epitopes were identified by using
      the computer programs available as a part of the Genetics Computer Group package
      and applying the information on allele-specific peptide motifs and intracellular
      enzymatic cleavage patterns to the bovine viral diarrhea virus polyprotein.
      Several candidate peptides were found for each of the bovine lymphocyte antigens
      (BoLA)-A11, -A20, -HD1, and -HD6 whereas no peptide was found for BoLA-HD7. Based
      on this finding, the probable contribution of genomic segments of BVDV to the CTL
      response and strategies for recombinant vaccines are discussed.

PMID- 9237353
TI  - Identification of a strong promoter of bacteriophage MB78 that lacks consensus
      sequence around minus 35 region and interacts with phage specific factor.
AB  - A strong promoter of bacteriophage MB78 does not have minus 35 consensus sequence
      although it has a TGn motif immediately upstream of minus 10 sequence as well as
      the AT rich UP element. It is efficiently recognised by the sigma 70 RNA
      polymerase, however, a phage-specific factor competes with sigma 70 RNA
      polymerase for binding to this region, the binding of the factor being stronger
      than that of the polymerase. Contrary to the reports in the literature the
      polymerase appears not to bind to the UP element whereas the phage-specific
      factor does. The latter seems to be involved in the regulation of the promoter
      activity.

PMID- 9237354
TI  - Bovine rotavirus 993/83 shows a third subtype of avian VP7 protein.
AB  - VP7 genes of rotavirus (RV) 993/83 isolated from a German calf with diarrhea and
      of RV PO-13 isolated from a Japanese pigeon were sequenced. Alignment of the
      deduced VP7 amino acid sequence showed 98.8% sequence identity, while only 70%
      and 84% identity was seen with VP7 from chicken RV Ch-2 and turkey RV Ty-1,
      respectively. Over the antigenic regions A, B, and C mammalian RV 993/83 showed
      more aa identity with mammalian G3 RVs than with chicken RV Ch-2, which could
      explain the strong one-way cross-neutralization observed between RV 993/83 and G3
      RVs. Despite marked VP7 sequence diversity avian RVs could not be differentiated
      into distinct G types.

PMID- 9237355
TI  - Inter- and intra-patient sequence diversity among parainfluenza virus-type 1
      nucleoprotein genes.
AB  - Parainfluenza viruses (PIV) have been categorized into four discrete types (types
      1-4), based on antigenic similarities. Here is described an evaluation of
      nucleoprotein (NP) sequence variability among nine patients infected with the
      type 1 virus. The examination of short segments of the NP sequence was sufficient
      to define significant variability both within and between patient samples. These
      data, in conjunction with previous studies of hemagglutinin-neuraminidase and
      fusion protein sequences from PIV-infected patient populations suggest a lack of
      absolute stability among isolates within each virus type. Potentially, antigenic
      variability exists to the extent that an immune response elicited toward one
      isolate may not be fully protective against another of the same type. Thus,
      sequence variability could contribute to natural re-infections with PIV, as well
      as to previous vaccine failures. Results highlight the importance of analyzing
      viruses that break through vaccine-induced immunity, in order to measure the
      influence of virus diversity on PIV vaccine outcome.

PMID- 9237356
TI  - Insertion of tandem direct repeats consisting of avian leukosis virus LTR
      sequences into the inverted repeat region of Marek's disease virus type 1 DNA.
AB  - The BC-1 strain DNA of Marek's disease virus type 1 (MDV1) at high-passage in
      culture was found to contain tandem direct repeats of the complete long terminal
      repeat (LTR) sequence of avian leukosis virus RAV0 strain as the repeat unit
      within the short inverted repeats of the MDV1 DNA. Since the attenuated BC-1
      strain grows well in cultured cells, the insertion site for retroviral DNA
      sequence within the short inverted repeat of MDV1 DNA is not essential for viral
      growth in culture.

PMID- 9237357
TI  - A member of the immunoglobulin superfamily in bacteriophage T4.
AB  - We report a prediction that the highly immunogenic outer capsid (Hoc) protein of
      the prokaryotic phage T4 contains three tandem immunoglobulin-like domains.
      Immunoglobulin-like folds have previously been identified in prokaryotic proteins
      but these share no recognizable sequence similarity with eukaryotic
      immunoglobulin superfamily (IgSF) folds, and may represent products of convergent
      evolution. In contrast, the Hoc immunoglobulin-like folds are proposed, based on
      immunoglobulin-like sequence consensus matches detected by hidden Markov
      modeling. We propose that the Hoc immunoglobulin-like domains and eukaryotic
      immunoglobulin-like domains are likely to be related by divergence from a common
      ancestor.

PMID- 9237358
TI  - Population coding of arm-movement-related neurons in and below the superior
      colliculus of Macaca mulatta.
AB  - It has been shown for the motor cortex of primates, that an arm trajectory is
      coded as a population vector formed by many neurons with activities correlated
      with arm movements. Recently, neurons in the primate superior colliculus that
      also display activities related to arm movements have been described. In the
      present paper we show that a subpopulation of this type of neuron is able to code
      for limb movement by the population vector. However, the cosine function cannot
      describe these neurons adequately. Rather the Fisher distribution yields a much
      better description of arm-movement-related cells in the superior colliculus.

PMID- 9237359
TI  - Spectral properties of human cognition and skill.
AB  - Many interactive human skills are based on real-time error detection and
      correction. Here we investigate the spectral properties of such skills, focusing
      on a synchronization task. A simple autoregressive error correction model, based
      on separate 'motor' and 'cognitive' sources, provides an excellent fit to
      experimental spectral data. The model can also apply to recurrent processes not
      based on error correction, allowing commentary on previous claims of 1/f-type
      noise in human cognition. A comparison of expert and non-expert subjects suggests
      that performance skill is not only based on reduced variance and bias, but also
      on the construction of richer mental models of error correction.

PMID- 9237360
TI  - Simulation of nonstationary EEG.
AB  - In this paper we present a systematic method for generating simulations of
      nonstationary EEG. Such simulations are needed, for example, in the evaluation of
      tracking algorithms. First a state evolution process is simulated. The states are
      initially represented as segments of stationary autoregressive processes which
      are described with the corresponding predictor coefficients and prediction error
      variances. These parameters are then concatenated to give a piecewise time
      invariant parameter evolution. The evolution is projected onto an appropriately
      selected set of smoothly time-varying functions. This projection is used to
      generate the final EEG simulation. As an example we use this method to simulate
      the EEG of a drowsy rat. This EEG can be described as toggling between two states
      that differ in the degree of synchronization of the activity-inducing neuron
      clusters.

PMID- 9237361
TI  - Coarse coding: calculation of the resolution achieved by a population of large
      receptive field neurons.
AB  - Electrophysiological studies in various sensory systems of different species show
      that many neurons involved in object localization have large receptive fields.
      This seems to contradict the high sensory resolution and the behavioral precision
      observed in localization experiments. Assuming a coarse coding mechanism, the
      resolution obtained by an ensemble of neurons is analytically calculated as a
      function of receptive field size. It is shown that particularly large receptive
      fields yield a high resolution.

PMID- 9237362
TI  - Emergence of clusters in the hidden layer of a dynamic recurrent neural network.
AB  - The neural integrator of the oculomotor system is a privileged field for
      artificial neural network simulation. In this paper, we were interested in an
      improvement of the biologically plausible features of the Arnold-Robinson
      network. This improvement was done by fixing the sign of the connection weights
      in the network (in order to respect the biological Dale's Law). We also
      introduced a notion of distance in the network in the form of transmission delays
      between its units. These modifications necessitated the introduction of a general
      supervisor in order to train the network to act as a leaky integrator. When
      examining the lateral connection weights of the hidden layer, the distribution of
      the weights values was found to exhibit a conspicuous structure: the high-value
      weights were grouped in what we call clusters. Other zones are quite flat and
      characterized by low-value weights. Clusters are defined as particular groups of
      adjoining neurons which have strong and privileged connections with another
      neighborhood of neurons. The clusters of the trained network are reminiscent of
      the small clusters or patches that have been found experimentally in the nucleus
      prepositus hypoglossi, where the neural integrator is located. A study was
      conducted to determine the conditions of emergence of these clusters in our
      network: they include the fixation of the weight sign, the introduction of a
      distance, and a convergence of the information from the hidden layer to the
      motoneurons. We conclude that this spontaneous emergence of clusters in
      artificial neural networks; performing a temporal integration, is due to
      computational constraints, with a restricted space of solutions. Thus,
      information processing could induce the emergence of iterated patterns in
      biological neural networks.

PMID- 9237363
TI  - Specialization in multi-agent systems through learning.
AB  - Specialization is a common feature in animal societies that leads to an
      improvement in the fitness of the team members and to an increase in the
      resources obtained by the team. In this paper we propose a simple reinforcement
      learning approach to specialization in an artificial multi-agent system. The
      system is composed of homogeneous and non-communicating agents. Because there is
      no communication, the number of agents in the team can easily scale up. Agents
      have the same initial functionalities, but they learn to specialize and so
      cooperate to achieve a complex gathering task efficiently. Simulation experiments
      show how the multi-agent system specializes appropriately so as to reach optimal
      (or near-to-optimal) performance in unknown and changing environments.

PMID- 9237364
TI  - Control of computational dynamics of coupled integrate-and-fire neurons.
AB  - Generation and control of different dynamical modes of computational processes in
      a net of interconnected integrate-and-fire neurons are demonstrated. A net
      architecture resembling a generic cortical structure is formed from pairs of
      excitatory and inhibitory units with excitatory connections between and
      inhibitory connections within pairs. Integrate-and-fire model neurons derived
      from detailed conductance-based models of neocortical pyramidal cells and fast
      spiking interneurons are employed for the excitatory and inhibitory units,
      respectively. Firing-rate adaptation is incorporated into the excitatory units
      based on the regulation of the slow afterhyperpolarization phase of action
      potentials by intracellular calcium ions. Saturation of synaptic conductances is
      implemented for the interconnections between units. It is shown that neuronal
      adaptation of the excitatory units can generate richer net dynamics than
      relaxation to fixed-point attractors-in a pattern space. At strong adaptivity,
      i.e. when the neuronal excitability is strongly influenced by the preceding
      activity, complex dynamics of either aperiodic or limit-cycle character are
      generated in both the pattern space and the phase space of all dynamical
      variables. This regime corresponds to an exploratory mode of the system, in which
      the pattern space can be searched. At weak adaptivity, the dynamics are governed
      by fixed-point attractors in the pattern space, and this corresponds to a mode
      for retrieval of a particular pattern. In the brain, neuronal adaptivity can be
      regulated by various neuromodulators. The results are in accordance with those
      recently obtained by means of more abstract models formulated in terms of mean
      firing rates. The increased realism makes the present model reveal more detailed
      mechanisms and strengthens the relevance of the conclusions to biological
      systems. The simplicity and realism of the coupled integrate-and-fire neurons
      make the present model useful for studies of systems in which the temporal
      aspects of neural coding are important.

PMID- 9237365
TI  - Immunodetection of cytoskeletal structures and the Eg5 motor protein on deep-etch
      replicas of Xenopus egg cortices isolated during the cortical rotation.
AB  - We have developed a new method for immunogold detection on deep-etch replicas of
      isolated Xenopus egg cortices in order to examine the interactions of different
      cortical elements in three dimensions at high resolution. We have applied this
      technique to vegetal cortices isolated during the second half of the first cell
      cycle. The vegetal cortical region at this time is the site of cellular machinery
      responsible for the 'cortical rotation'. The entire cortex translocates with
      respect to the inner cytoplasm, relocating dorsalising determinants to the future
      dorsal side of the egg. The aligned microtubules in the shear zone between
      cytoplasm and cortex, implicated in the cortical rotation, were found to be
      organised as interweaving loose bundles. Interleaved amongst these aligned
      microtubules were extensive sheets of ER lying in layers parallel to the egg
      surface. Cytokeratin filaments were found to associate closely with the
      microtubules over short stretches. Putative actin filaments were present in the
      shear zone and in the cortex. Eg5, an abundant kinesin-related microtubule motor
      protein, and candidate for a role in generating cortical rotation movement,
      showed an almost exclusive localisation to microtubules. Immunofluorescence
      studies of cortices treated with detergent to disrupt ER or cold to depolymerise
      microtubules confirmed that Eg5 associates primarily with microtubules. We
      propose revised models for the mechanism of cortical rotation based on these
      observations and conclude that Eg5 is unlikely to move ER relative to
      microtubules during the cortical rotation.

PMID- 9237366
TI  - Xenopus cyclin D2: cloning and expression in oocytes and during early
      development.
AB  - We have isolated and characterized a cDNA which contains the entire coding
      sequence of Xenopus laevis cyclin D2 protein. Cyclin D2 mRNA is identified as a
      member of the class of maternal RNAs. It is rare and stable during embryonic
      development at least until tadepole. In addition, a second cDNA coding for a
      truncated version of cyclin D2 was also isolated. Microinjection of cyclin D2
      into oocytes undergoing meiotic maturation and parthenogenetic activation reveals
      that the protein is stable for several hours, independently of the ubiquitin
      mediated degradation of cyclin B2 that takes place periodically during this
      process. Microinjected cyclin D2 localizes both in the cytoplasm and in the
      nucleus of oocyte. In somatic cells, it is well established that cyclin D2 is
      almost exclusively nuclear and very labile. The unusual behaviour of cyclin D2
      upon injection into oocytes may provide indications about a possible role for
      this protein during meiosis and early development.

PMID- 9237367
TI  - Small GTP-binding proteins in Plasmodium falciparum.
AB  - During its erythrocytic life cycle Plasmodium falciparum exchanges compounds with
      host cells through phagocytosis and exocytosis. In eucaryotic cells, small GTP
      binding proteins of the Ras superfamily appear to be involved in different steps
      of membrane trafficking and in intracellular signals. In this paper, we
      investigate the Rab4, Rab6 and Ras-related proteins in P falciparum infected red
      cells. We report that P falciparum Rab and Ras-related proteins could be
      distinguished from their counterparts by iso-electrofocusing and immunoblotting.
      The localization of P falciparum Rab 4 and Rab 6 was studied by immunogold
      electron microscopy on ultrathin frozen sections of infected red blood cells.
      Rab4 parasite-related protein was found associated with the membranes of early
      endosome-like structures near the parasite plasma membrane. Rab6-related protein
      was associated with the Golgi/trans Golgi network, as already suggested by
      immunofluorescence microscopy studies and Ras-related protein was cytoplasmic and
      plasma membrane-associated. These results are in accordance with their mammalian
      counterparts and support the implication of Rab-related proteins in vesicular
      trafficking in Plasmodium.

PMID- 9237368
TI  - Identification and subcellular distribution of the Gi-proteins in the enterocytic
      differentiated adenocarcinoma cell-line, Caco-2.
AB  - As evidenced by pertussis toxin-catalysed [32P]ADP-ribosylation, immunoblotting
      and Northern blot, the human adenocarcinoma intestinal cell line Caco-2 expresses
      Gi2 and Gi3 proteins. The localization of these two Gis within the cell was
      investigated by using subcellular fractionation and confocal microscopy on intact
      cell layer. A brush-border rich fraction and a pellet containing the remaining
      cellular membranes were prepared. [32P]ADP-ribosylation and immunoblotting
      demonstrated the presence of both alpha i2 and alpha i3 in these two
      preparations. Immunofluorescence studies performed on intact cells grown on
      Transwell filters and viewed by confocal microscopy further confirmed the
      localization of alpha i3-subunit on basolateral as well as on apical membranes.
      In contrast, alpha i2-subunit was shown to accumulate mainly in the intra
      cellular compartment while only faint staining of the plasma membrane was
      detectable. Based upon double-labelling experiments with antibody against rough
      endoplasmic reticulum (RER), there is a strong possibility that intra-cellular
      sites of alpha i2-subunit correspond to association with RER membranes.

PMID- 9237369
TI  - Analysis of skeletal and cardiac muscle from desmin knock-out and normal mice by
      high resolution separation of myosin heavy-chain isoforms.
AB  - In this study, using a modified electrophoretic technique, we have defined in the
      mouse the myosin heavy-chain composition of both newborn and adult skeletal and
      cardiac muscles. Using this high resolution technique it was possible to detect
      modifications in the myosin heavy-chain expression in both cardiac and skeletal
      muscles of desmin knock-out mice.

PMID- 9237370
TI  - Immunocytochemical localization of arabinoxylans in the cell wall of maize apical
      internode after microbial degradation in the rumen.
AB  - Arabinoxylans were localised by immunocytochemistry using polyclonal antibodies
      in the cell walls of the apical internode of maize after degradation in the
      rumen. In order to understand the significance of arabinoxylan in digestibility
      property, two lines of maize differing in digestibility were used. Wide
      variations in the intensity of labelling were observed in the four tissues
      studied (sclerenchyma, fibres, xylem and parenchyma) from the first hours of
      incubation in the rumen. Incubation time in the rumen greatly influences the
      intensity of labelling.

PMID- 9237371
TI  - A mini organ culture as a model for studying the gallbladder epithelium of mouse.
AB  - A mini organ culture of mouse gallbladder was developed as an alternative to
      primary cultures of epithelial cells of this organ. Small pieces of tissue were
      prepared and maintained in minimum essential Eagle medium with 10% foetal calf
      serum, for as long as 7 days. Qualitative and quantitative ultrastructural
      studies have been performed using electron microscopy. The viability of cells was
      evaluated by stereological quantification of endocytotic vesicles containing
      horseradish peroxidase and labelling of exocytotic glycoproteins with tannic
      acid. The morphology of tissue pieces during the 1st h of culturing and tissue
      isolated directly from animals exhibited no significant differences. However,
      after 4 h in culture degradative changes became evident in many cells. At that
      time, endo- and exocytosis were both dramatically reduced. After 24 h, the
      morphology, as well as endo- and exocytosis recovered and were comparable to the
      parameters of the tissue in vivo or after 1 h in culture. The endocytotic
      activity remained unchanged from day 1 to 7 of culturing, while the number of
      exocytotic vesicles gradually decreased after 2 days in culture. Our results
      prove that mini organ culture of gallbladder is morphologically and functionally
      comparable with the tissue in vivo and for studies of epithelium in culture it is
      more convenient than primary cultures.

PMID- 9237372
TI  - Analysis of wool fiber by alkali-catalyzed pyrolysis gas chromatography.
AB  - Alkali-catalyzed pyrolysis gas chromatography (PyGC) has been used to identify
      minute samples of wool fiber. The wool sample to which aqueous sodium hydroxide
      was added was pyrolyzed in a Curie-point pyrolyzer attached to a gas
      chromatograph or a gas chromatograph-mass spectrometer. The addition of an
      aqueous solution of sodium hydroxide increased the production of specific
      volatile pyrolysis products from the constitutive amino acid residues of wool
      protein, i.e. acetaldehyde from alanine or proline, isobutyronitrile from valine,
      2-methylbutyronitrile from isoleucine, isovaleronitrile from leucine and toluene
      from phenylalanine. Compared with conventional non-catalyzed PyGC, the alkali
      catalyzed PyGC was found to greatly improve the detection limit of wool fiber and
      make it possible to analyze very minute samples. The alkali-catalyzed PyGC
      presented here has been shown to be applicable to minute thermally-denatured
      samples of wool fiber which cannot be identified successfully by morphological
      inspection using a microscope or by using Fourier-transform infrared
      microspectroscopy. Furthermore, the present PyGC method was successfully used for
      several protein samples and was shown to be useful for analysis of proteins other
      than wool fibers by using different special pyrograms reflecting different amino
      acid compositions.

PMID- 9237373
TI  - Sequence variation of mitochondrial DNA control region in Koreans.
AB  - The sequencing data for two mtDNA segments in control region I and II, 385 and
      341 nucleotides long, respectively, for 306 unrelated Koreans are presented. In
      regions I and II, 139 and 58 polymorphic sites, respectively, were noted. These
      were distributed evenly along the control region, though the frequency of each
      site was variable. Nucleotide substitution rather than insertion/deletion was the
      prevalent pattern of variation. A total of 265 different mtDNA lineages in region
      I and 154 in region II were revealed. This result represents a substantial level
      of polymorphism in a defined population, and presents the possibility that mtDNA
      polymorphism could be used as an individual identification marker, especially
      when nuclear DNA is not available. In view of the complex pattern of variation,
      meticulous test-sequencing is thought to be more appropriate than RFLP analysis
      using restriction endonuclease or hybridization using an SSO probe. Racial
      differences with genealogical usage are also described.

PMID- 9237374
TI  - Muti or ritual murder.
AB  - Ritual or muti murders are a form of human sacrifice practised by some African
      tribes. The murder is carried out after body parts are removed while the victim
      is still alive. This case report describes the methods of identification of a
      young child who was murdered by a traditional healer (isangoma) in Cape Town, and
      the practice of the traditional healer.

PMID- 9237375
TI  - The screening of 13 short tandem repeat loci in the Chinese population.
AB  - Population studies of 13 short tandem repeat (STR) loci were carried out on
      Chinese in Taiwan. The STR loci included HUMF13B, HUMF13A01, HUMFES/FPS, HUMFABP,
      HUMPLA2A1, HUMTPOX, HUMTH01, HUMVWFA31/A, HUMCSFIPO, HUMLPL, HUMGPP3A09,
      HUMCYAR04 and HUMCD4. DNA samples from 100 unrelated individuals were screened.
      The STR allele patterns were detected by the fluorescence detector of an
      automated DNA sequencer. Two PCR amplifications were performed for each STR locus
      in this study. The first PCR amplification strategy used 26 base pairs of the T7
      sequence extension in the 5' end of the forward primer of each STR locus. The
      second PCR amplification used a dye-labeled T7 primer instead of the forward
      primer in the first PCR amplification, and the first PCR products as template to
      produce fluorescent dye-labeled PCR products. PCR products of different STR loci
      with overlapping allele sizes could be detected in the same lane of the
      polyacrylamide gel on an automated DNA sequencer using different colored dye
      labeled T7 primers. There was no need to directly conjugate the fluorescent dye
      to individual STR primers. The PCR products were obtained using 2 ng of template
      DNA in 25 microliters of PCR reaction mixture. No deviations from the Hardy
      Weinberg equilibrium were observed for the 13 STR loci. The distributions of
      these STR alleles were different from those of Caucasians or Blacks. The
      probability of matching from the combination of the 13 STR loci was 5.9 x 10(-10)
      for our Chinese population. However, HUMF13B, HUMLPL and HUMCD4 loci were not as
      highly polymorphic as observed in other populations.

PMID- 9237376
TI  - A sandwich enzyme immunoassay for brain S-100 protein and its forensic
      application.
AB  - A sensitive sandwich enzyme immunoassay for identification of brain S-100 protein
      in blood or bloodstains containing brain tissue is described. A polystyrene ball
      coated with rabbit anti-S-100 protein IgG was incubated with human S-100 protein,
      and then with anti-S-100 Fab'-peroxidase conjugate. Peroxidase activity bound to
      the polystyrene ball was assayed by fluorometry using 3-(4
      hydroxyphenyl)propionic acid as the hydrogen donor. The detection limit of human
      S-100 protein was 0.6 pg (30 amol) per assay tube. The cross-reaction of this
      sandwich enzyme immunoassay to other organs was approximately 1/100 or less.
      Antigenic activity of S-100 protein in bloodstains containing brain extracts was
      detectable after storage for 36 days at room temperature. The ratio of S-100
      protein to total protein (ng/mg) in bloodstains when brain tissue was mixed with
      normal human blood at concentrations of 5-500 mg/ml was approximately 100-fold
      those of other samples (liver, heart, intestine, and skeletal muscle). These
      results indicated that bloodstains mixed with brain tissue were clearly
      distinguishable from others. Thus, in forensic practice, measurement of S-100
      protein or the ratio of S-100 protein to total protein is useful to identify
      blood and bloodstains containing brain tissue.

PMID- 9237377
TI  - The significance of fibres found in head hair.
AB  - The incidence of four common fibres in the head hair of 100 individuals has been
      established. A total of 37 matching fibres were found in the hair of 22 people
      with a maximum of five fibres on any one head. Two subjects had fibres matching
      two sources in their hair.

PMID- 9237378
TI  - Fatal inhalation of 1,1,1-trichloroethane.
AB  - A 13-year-old male was found dead in the woods subsequent to 1,1,1
      trichloroethane (TCE) inhalation. Autopsy findings included tissue congestion of
      lung, liver and kidney. Certain precautions were taken in collecting and storing
      biological samples in order to prevent loss of TCE by evaporation. The
      availability of volatile solvents coupled with the increase of volatile substance
      abuse makes it easy for abusers to obtain.

PMID- 9237379
TI  - Concerning the paper by Herczeg et al., entitled: 'Morphological damage to the
      central nervous system (CNS) following open heart surgery' (Forensic Sci. Int.,
      79 (1996) 103-111)

PMID- 9237380
TI  - Concerning the paper by Baccino et al., entitled: 'Outer ear temperature and time
      of death' (Forensic Sci. Int., 83 (1996) 133-146)

PMID- 9237382
TI  - Distribution and characterization of Enterococcus species in municipal sewages.
AB  - The occurrence, distribution and characterization of enterococci in municipal
      sewages from two geographically different regional sewage treatment plants in
      East Slovakia was studied. The total counts of enterococci in samples varied from
      10(4) to 10(6) CFU/ml. The vast majority of the strains identified were
      Enterococcus faecium (50%), with E. gallinarum (25.5%) and E. casseliflavus
      (10.1%). The species which accounted for 14.4% of the cultures were not
      specified. Lactic acid production from twenty isolates ranged from 0.085 mol l-1
      to 0.914 mol l-1. Urease activity ranged from 1.21 nkat ml-1 to 10.49 nkat ml-1.
      The strains were resistant to at least one (except for vancomycin) and at most to
      six antibiotics tested. The majority of isolates were biresistant. Although nine
      strains were without bacteriocin production, the other strains inhibited the
      growth of enterococcal as well as staphylococcal isolates. E. faecium AL 40
      produced bacteriocin which inhibited the growth of all indicators reaching 12 mm
      zones of inhibition. E. faecium was the most prevalent species in all samples,
      but the source position of isolates as well as the sewage composition did not
      affect enterococcal distribution. The ability of isolates to produce bacteriocin
      indicates their possible use in biotechnological environmental processes.

PMID- 9237383
TI  - Effects of the amino sugars, glucosamine, mannosamine, or the fluorinated
      derivative 2-deoxy-fluoroglucose on the phosphatidyl inositol and glycosyl
      phosphatidyl inositol systems of Tetrahymena.
AB  - Sugar derivatives which have an inhibitory effect on glycosyl phosphatidyl
      inositol (GPI) synthesis in mammals, primarily prevented 32P incorporation in the
      unicellular Tetrahymena. Incorporation of 3H-mannose and 3H-inositol was induced
      by mannosamine. While there was a uniform effect of sugar analogues in mammals,
      they could not elicit totally similar effects in Tetrahymena. Analogues of sugar
      also affected synthesis in the phosphatidyl inositol (PI) system. Synthesis of
      GPI in Tetrahymena was different from that in mammals, but the metabolism of GPI
      and PI revealed similarities.

PMID- 9237384
TI  - Acinetobacter radioresistens metabolizing aromatic compounds. 2. Biochemical and
      microbiological characterization of the strain.
AB  - The metabolic potentialities of an Acinetobacter radioresistens strain, isolated
      from the soil adjacent to an activated sludge plant, were investigated. Among 26
      aromatic substrates tested, only phenol, benzoate and catechol were metabolized.
      Since this strain possessed abundant plasmid DNA, the antibiotic and heavy metal
      resistance was examined, and the bacterial cells proved to be sensitive to all
      metals (Ni, Tl, Pb, Cd, Ag, Co, Zn) and antibiotics tested except for Fosfomycin
      and chloramphenicol. The degradation kinetics for phenol and benzoate as the sole
      carbon/energy source (pH 7, 30 degrees C) displayed different trends, confirmed
      by the bacterial growth curve. Crude extracts from phenol-grown cultures showed
      both phenol hydroxylating activity and catechol dioxygenating activity. Phenol
      hydroxylase possessed a reductase component able to reduce nitroblue tetrazolium
      (NBT) and cytochrome C, thus exhibiting differences from previously reported
      monocomponent phenol hydroxylases from the same genus. Catechol dioxygenase is an
      intradiol-cleaving enzyme recognizing also substituted catechols.

PMID- 9237385
TI  - Reducing medium for the cultivation of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, a micro-organism frequently associated with human
      periodontal diseases, is commonly cultured under a reducing atmosphere in
      enclosed cabinets or glove boxes. This paper reports a modified Wilkins-Chalgren
      (MWC) medium for the culture of P. gingivalis under atmospheric conditions at 37
      degrees C. On the basis of preliminary tests, WC broth was supplemented as
      follows: 500 mg/l cysteine hydrochloride; 250 mg/l sodium thioglycolate; and
      1,000 mg/l sodium bicarbonate. Three P. gingivalis isolates (JKG-I, 33277 and
      A7436) showed very similar growth over 24 and 48 h periods when cultured both in
      WC medium in an anaerobic chamber and in the MWC medium. Culture of these
      isolates both in the anaerobic chamber and in the MWC medium yielded very similar
      data with respect to trypsin-like activity, total protease activity, and
      reactivity to monoclonal antibodies specific for P. gingivalis. Growth in the MWC
      medium varied over a 3- to 4-fold range for seven additional isolates (JKG-7,
      D86B6, D13B11, D84D2, JKG9, D67D9, D82F5) over 24 and 48 h periods.

PMID- 9237386
TI  - Development of a low-cost fermentation medium for ethanol production from
      biomass.
AB  - Nutrient cost is an important aspect in the fermentation of biomass to ethanol.
      With a goal of developing a cost-effective fermentation medium, several
      industrially available nutrient sources were evaluated for their effectiveness in
      the simultaneous saccharification and fermentation of pretreated poplar with
      Saccharomyces cerevisiae D5A. These studies showed that a low-cost medium
      containing 0.3% corn steep liquor and 2.5 mM MgSO4 7H2O was similar in
      performance to a nutrient-rich medium. Besides its low cost, this alternative
      medium consists of components that are available on a commercial scale, thereby
      making it industrially relevant.

PMID- 9237387
TI  - Activity of Pseudomonas cepacia lipase in organic media is greatly enhanced after
      immobilization on a polypropylene support.
AB  - The purified lipase from Pseudomonas cepacia was used as free and immobilized
      enzyme preparation for hydrolysis of p-nitrophenyl palmitate (pNPP) and p
      nitrophenyl acetate (pNPA) in organic media. The free enzyme was mixed with
      bovine serum albumin and lyophilized. Immobilization was on porous polypropylene.
      Conditions where diffusional limitations of the substrate were not limiting the
      reaction rate were defined. The specific activity of the lipase was greatly
      enhanced upon immobilization: 16.5- and 7.8-fold for pNPP and pNPA respectively.
      Both the free and immobilized lipases followed Michaelis-Menten kinetics in
      organic solvent despite the heterogeneity (solid/liquid) of the reaction mixture.
      For pNPP, the activation factor upon immobilization came mainly from a reduction
      in Km)app while kcat was increased for pNPA.

PMID- 9237388
TI  - Isolation and characterization of highly (R)-specific N-acetyl-1-phenylethylamine
      amidohydrolase, a new enzyme from Arthrobacter aurescens AcR5b.
AB  - A new amidohydrolase deacetylating several N-acetyl-1-phenylethylamine
      derivatives (R)-specifically was found in Arthrobacter aurescens AcR5b. The
      strain was isolated from a wet haystack by enrichment culture with (R)-N-acetyl-1
      phenylethylamine as the sole carbon source. (R) and (S)-N-acetyl-1
      phenylethylamine do not serve as inducers for acylase formation. By improving the
      growth conditions the enzyme production was increased 47-fold. The amidohydrolase
      was purified to homogeneity leading to a 5.2-fold increase of the specific
      activity with a recovery of 67%. A molecular mass of 220 kDa was estimated by gel
      filtration. Sodium dodecyl sulfate/polyacrylamide gel electrophorosis shows two
      subunits with molecular masses of 16 kDa and 89 kDa. The optimum pH and
      temperature were pH 8 and 50 degrees C, respectively. The enzyme was stable in
      the range of pH 7-9 and at temperatures up to 30 degrees C. The enzyme activity
      was inhibited by Cu2+, Co2+, Ni2+, and Zn2+, and this inhibition was reversed by
      EDTA.M.

PMID- 9237389
TI  - Cloning and expression of the delta 9 fatty acid desaturase gene from
      Cryptococcus curvatus ATCC 20509 containing histidine boxes and a cytochrome b5
      domain.
AB  - To allow genetic modification of the fatty acid biosynthesis routes in the lipid
      accumulating yeast Cryptococcus curvatus the delta 9 fatty acid desaturase gene
      was cloned and characterized. The 1668-bp gene encodes a protein of 556 amino
      acids with a calculated molecular mass of 62 kDa. The gene shows strong homology
      to previously cloned delta 9 fatty acid desaturase genes from yeast and rat.
      Homology includes three histidine boxes characteristic for membrane-bound
      desaturases and a cytochrome b5 domain responsible for electron transport. The
      delta 9 desaturase gene has a high G+C content of 61% and displays a codon usage
      different from that of Saccharomyces cerevisiae, but similar to that of the
      basidiomycete Schizophyllum commune. Expression of the delta 9 desaturase gene of
      C. curvatus ATCC 20509 was studied in the presence of different fatty acids in
      the growth medium. Repression of desaturase mRNA signals was found if fatty acids
      with a double bond at the delta 9 position were present. Fatty acids with a
      double bond at another position (delta 10 or delta 6) or saturated fatty acids
      had no effect on the transcription of the cloned gene.

PMID- 9237390
TI  - Pentachlorophenol biodegradation kinetics of an oligotrophic fluidized-bed
      enrichment culture.
AB  - A fluidized-bed reactor (FBR) was used to enrich an aerobic chlorophenol
      degrading microbial culture. Long-term continuous-flow operation with low
      effluent concentrations selected oligotrophic microorganisms producing good
      quality effluent for pentachlorophenol(PCP)-contaminated water. PCP
      biodegradation kinetics was studied using this FBR enrichment culture. The
      results from FBR batch experiments were modeled using a modified Haldane
      equation, which resulted in the following kinetic constants: qmax = 0.41 mg PCP
      mg protein-1 day-1, Ks = 16 micrograms l-1, Ki = 5.3 mg l-1, and n = 3.5. These
      results show that the culture has a high affinity for PCP but is also inhibited
      by relatively low PCP concentrations (above 1.1 mg PCP l-1). This enrichment
      culture was maintained over 1 year of continuous-flow operation with PCP as the
      sole source of carbon and energy. During continuous-flow operation, effluent
      concentrations below 2 micrograms l-1 were achieved at 268 min hydraulic
      retention time (tHR) and 2.5 mg PCP l-1 feed concentration. An increase in
      loading rate by decreasing tHR did not significantly deteriorate the effluent
      quality until a tHR decrease from 30 min to 21 min resulted in process failure.
      Recovery from process failure was slow. Decreasing the feed PCP concentration and
      increasing tHR resulted in an improved process recovery.

PMID- 9237391
TI  - The de novo production of drosophilin A (tetrachloro-4-methoxyphenol) and
      drosophilin A methyl ether (tetrachloro-1,4-dimethoxybenzene) by ligninolytic
      basidiomycetes.
AB  - Ligninolytic basidiomycetes were screened for their ability to produce the
      tetrachlorinated hydroquinone metabolites drosophilin A (DA, tetrachloro-4
      methoxyphenol) and drosophilin A methyl ether (DAME, tetrachloro-1,4
      dimethoxybenzene). Five fungal strains produced these metabolites in detectable
      amounts, including strains from Bjerkandera and Peniophora, which are genera not
      previously known for DA or DAME production. Phellinus fastuosus ATCC26.125 had
      the highest and most reliable production of DA and DAME in peptone medium,
      respectively 15-60 microM and 4-40 microM. This fungus was used to study culture
      conditions that could increase DAME production. A fourfold increase in DAME
      production was found after the addition of hydroquinone to growing cultures of P.
      fastuosus. Therefore, hydroquinone is postulated to be a possible biosynthetic
      precursor of DAME in the fungus. Antagonising P. fastuosus by adding filter
      sterilised culture fluid of a competing fungus, Phlebia radiata, increased DAME
      production significantly by tenfold. This result suggests that DAME production is
      elicited by compounds present in the culture fluid of P. radiata, indicating that
      DAME has an antibiotic function in P. fastuosus.

PMID- 9237392
TI  - Diacetyl and acetoin production from the co-metabolism of citrate and xylose by
      Leuconostoc mesenteroides subsp. mesenteroides.
AB  - The co-metabolism of citrate plus xylose by Leuconostoc mesenteroides subsp.
      mesenteroides results in a growth stimulation, an increase in D-lactate and
      acetate production and repression of ethanol production. This correlated well
      with the levels of key enzymes involved. A partial repression of alcohol
      dehydrogenase and a marked stimulation of acetate kinase were observed. High
      citrate bioconversion yields in diacetyl plus acetoin were obtained at pH 5.2 in
      batch (11.5%) or in chemostat (up to 17.4%) culture. In contrast, no diacetyl or
      acetoin was detected in citrate plus glucose fermentation.

PMID- 9237393
TI  - Rapid method for detecting Desulfitobacterium frappieri strain PCP-1 in soil by
      the polymerase chain reaction.
AB  - A rapid method was developed for detecting in soil Desulfitobacterium frappieri
      strain PCP-1, an anaerobic gram-positive bacterium, isolated from a methanogenic
      consortium degrading pentachlorophenol. The method involved the establishment of
      a protocol for extracting total DNA from soil with the least contamination, and
      the use of the polymerase chain reaction (PCR) to detect strain PCP-1 with
      primers targeted with PCP-1 16S rRNA. To optimize the DNA extraction conditions,
      a glass mill homogenizer and a low-salt buffer containing
      polyvinylpolypyrrolidone were used on a black soil rich in organic matter.
      Recovered DNA was further purified with phenol/chloroform extractions, ammonium
      acetate precipitation and a G200 Sephadex gel-filtration column. DNA was
      extracted from soil supplemented with different concentrations of PCP-1 cells.
      Detection of PCP-1 was by PCR. The limit of detection was 800 added PCP-1 cells/g
      dry soil. This level of detection was achieved when the T4 gene-32 protein and 1
      microgram soil DNA were added to the PCR mixture followed by a nested PCR. This
      method is quick, sensitive, and can process several samples at the same time.

PMID- 9237394
TI  - Sequence and structural features of plant and fungal tyrosinases.
AB  - Tyrosinases from various organisms are compared with respect to enzymatic
      structure, primary, secondary and tertiary structure, domain structure, Cu
      binding sites, maturation mechanism and activation mechanism. On the basis of
      these comparisons, and by using hemocyanin structure as a template, a structure
      model for the active site of tyrosinases is proposed.

PMID- 9237395
TI  - Brassinosteroids from seeds of Arabidopsis thaliana.
AB  - Extracts of seeds of Arabidopsis thaliana (ecotype 24) were analysed for the
      presence of free and conjugated brassinosteroids. 24-epi-Brassinolide (ca 220 ng
      kg-1) and castasterone (ca 360 ng kg-1) could be isolated and unambiguously
      identified as native brassinosteroids by GC/MS.

PMID- 9237396
TI  - Varietal differences in protein phosphorylation during cold treatment of rice
      leaves.
AB  - The effects of cold stress on protein phosphorylation in leaves of rice (Oryza
      sativa) seedlings were investigated. Two-week-old rice seedlings were exposed to
      low temperature (5 degrees) for 6 hr at a relative humidity of 100%. The leaf
      protein extracts were phosphorylated in vitro. Cold stress stimulated the
      phosphorylation of a 60 kDa protein in the cold-sensitive rice variety, IR36. In
      the cold-tolerant rice variety, Kitaibuki, this protein had already been
      phosphorylated. For greater clarificating of these changes, the effects of cold
      on rice varieties differing in cold susceptibility were examined. Cold-sensitive
      rice varieties showed similar the protein phosphorylation in contrast to the cold
      tolerant rice varieties.

PMID- 9237397
TI  - Properties of plasma membranes of Phsp 70-ipt transformed tobacco (Nicotiana
      tabacum).
AB  - Application of 10 successive daily heat shocks reduced the growth of control
      tobacco (Nicotiana tabacum L. cv. Petit Havana SR1) plants by about 15%; for Phsp
      70-ipt transformed plants this is about 48%. The shoot diameter of these ipt
      transformed plants increased by about 75%. In addition, in heat shock treated ipt
      plants (IPT-HS) the upper lateral buds grew out due to a reduction of apical
      dominance. The older leaves of IPT-HS plants had a higher chlorophyll content. In
      spite of the observed effects due to a higher endogenous cytokinin content in the
      IPT-HS plants, no significant changes were observed on the plasma membrane fatty
      acid composition, nor on its fluidity as determined from the steady-state
      fluorescence anisotropy of DPH. Only a minor change in the plasma membrane free
      sterol composition was found as evidenced by a 20% decrease in the stigmasterol
      to sitosterol ratio in IPT-HS, indicative for a possible anti-senescence effect
      of enhanced endogenous cytokinins, but without significant effects on the plasma
      membrane function.

PMID- 9237398
TI  - Cadmium- and copper-induced changes in tomato membrane lipids.
AB  - Cadmium and copper uptake and distribution, as well as their effects on growth
      and lipid composition were investigated in 17-day-old tomato seedlings
      (Lycopersicon esculentum Mill. cv. 63/5 F1) grown in culture solution supplied
      with two concentrations of Cd or Cu (0, 5 and 50 microM). The accumulation of Cd
      and Cu increased with external metal concentrations, and was considerably higher
      in roots than in primary leaves. Biomass production of the growing roots and
      primary leaves was strongly depressed at high metal levels. Also, significant
      decreases in the content of lipid classes and changes of fatty acid composition
      were recorded in heavy metal-stressed plants in comparison with controls.
      Glycolipid contents were decreased more in leaves than in roots by Cd-treatment,
      but copper decreased both to similar extents in both organs. Likewise, both
      metals reduced the phospholipid and neutral lipid contents more in roots than in
      leaves. In almost all lipid classes the proportion of palmitic acid (16:0)
      increased, and that of linoleic (18:2) or linolenic (18:3) acid decreased,
      suggesting that heavy metal treatment induced an alteration in the fatty acid
      desaturation processes. Furthermore, the accumulation of palmitate (16:0) rather
      than stearate (18:0) indicated an alteration in the ratio of products from the
      fatty acid synthase. Copper was found to be the most unfavourable for plant
      growth and lipid metabolism. The possible mechanisms by which heavy metals,
      especially Cu, induce a strong lipid shift are discussed.

PMID- 9237399
TI  - Pectinolytic enzymes from Pseudomonas marginalis MAFF 03-01173.
AB  - Two pectinolytic enzymes were purified from the culture broth of Pseudomonas
      marginalis pv. marginalis MAFF 03-01173 with total 33% recovery of the initial
      activity. From the substrate specificities against pectin and polygalacturonic
      acid, the requirement of calcium ion for the enzymatic activity, and the N
      terminal sequences, the enzymes were identified as pectin lyase and pectate
      lyase. The M,s of pectin lyase and pectate lyase were estimated to be 34,000 and
      43,000, respectively, by SDS polyacrylamide gel electrophoresis. Both enzymes
      showed almost the same pH dependent activity curves with the highest activity at
      pH 8.3

PMID- 9237400
TI  - Detection of tomatinase from Fusarium oxysporum f. sp. lycopersici in infected
      tomato plants.
AB  - The antifungal glycoalkaloid alpha-tomatine of the tomato plant (Lycopersicon
      esculentum) is proposed to protect the plant against phytopathogenic fungi.
      Fusarium oxysporum f. sp. lycopersici, a vascular pathogen of tomato, produces a
      tomatinase enzyme which hydrolyses the glycoalkaloid into non-fungitoxic
      compounds. Detoxification of alpha-tomatine may be how this fungus avoids the
      plant glycoalkaloid barrier. As an initial step to evaluate this possibility we
      have studied the induction of tomatinase; (i) in fungal cultures containing
      extracts from leaf, stem or root of tomato plants; and (ii) in stem and root of
      tomato plants infected with the pathogen at different infection stages. The
      kinetics of tomatinase induction with leaf extract (0.6% dry weight) was similar
      to that observed with 20 micrograms ml-1 of alpha-tomatine. In the presence of
      stem extract, tomatinase activity was less than 50% of that induced with leaf
      extract, whereas in the presence of root extract tomatinase activity was very
      low. In the stem of infected tomato plants tomatinase activity was higher at the
      wilt stage than in previous infections stages and in root, tomatinase activity
      appeared with the first symptoms and was maintained until wilting. TLC analysis
      showed that the tomatinase induced in culture medium with plant extracts and in
      infected tomato plants had the same mode of action as the enzyme induced with
      pure alpha-tomatine, hydrolysing the glycoalkaloid into its non-fungitoxic forms,
      tomatidine and beta-lycotetraose. The antisera raised against purified tomatinase
      recognized in extracts of root and stem of infected tomato plants a protein of
      50000 (45000 when proteins were deglycosylated), corresponding to the tomatinase
      enzyme. Therefore, it is concluded that F. oxysporum f. sp. lycopersici express
      tomatinase in vivo as a result of the infection of tomato plant.

PMID- 9237401
TI  - Biological activities of pseudomycin A, a lipodepsinonapeptide from Pseudomonas
      syringae MSU 16H.
AB  - Similarly to other Pseudomonas lipodepsinonapeptides, pseudomycin A inhibits
      proton extrusion from maize roots, promotes closure of stomata in Vicia faba,
      necrosis of tobacco leaves, haemolysis of human erythrocytes, affects H(+)-ATPase
      activity and proton translocation in plasma membrane vesicles, and stimulates
      succinate respiration in pea mitochondria. In general, the biological activities
      of pseudomycin A are lower than those of syringomycin-E, the prototype member of
      this family of bacterial metabolities. This difference might depend on the
      diverse number and distribution of charged residues in the peptide moiety of
      these compounds.

PMID- 9237402
TI  - Separation of the N-7 methyltransferase, the key enzyme in caffeine biosynthesis.
AB  - Caffeine biosynthesis comprises sequential methylations at N-7, N-3 and N-1 of
      the xanthine ring catalysed by S-adenosyl-L-methionine (SAM)-dependent
      methyltransferase activities that, to date, have not been resolved. Enzyme
      extracts were prepared from young, emerging coffee leaflets and following anion
      exchange chromatography, chromatofocusing facilitated the clear separation of the
      N-7-methyltransferase from the N-3- and N-1-methyltransferase activities. All
      three N-methyltransferases co-eluted when analysed by gel filtration
      chromatography and their native molecular mass was ca 67 kDa. Photoaffinity
      labelling with [methyl-3H]SAM followed by SDS-PAGE of a chromatofocusing-purified
      preparation containing only N-7-methyltransferase activity demonstrated the
      presence of a single labelled band of 40 kDa. Similar analysis of a gel
      filtration purified preparation containing all three N-methyltransferase
      activities revealed the presence of three labelled bands at 49, 43 and 40 kDa. It
      remains to be determined whether the 49 and 43 kDa bands are associated with the
      N-3 and N-1-methyltransferases or whether they are unrelated SAM-dependent
      methyltransferases or other SAM-binding proteins.

PMID- 9237403
TI  - Use of clinically relevant human-scid-mouse models in metastasis research.

PMID- 9237404
TI  - Some aspects of bioassay methods in natural-product research aimed at drug lead
      discovery.
AB  - The objective of natural-product research aimed at drug lead discovery is to find
      unique bioactive molecules with improved biopharmaceutical properties or new
      modes of action. In order to discover such bioactive substances, different
      bioassays are used for detection, for guidance of the chemical isolation
      procedures and for preliminary biological characterization of new compounds. This
      article gives a brief update on current biological activities and discusses some
      essential, but occasionally neglected, aspects of bioassay methods. Some future
      perspectives on the use of bioassay methods in the drug-discovery process are
      also discussed.

PMID- 9237405
TI  - Aspergillus as a host for heterologous protein production: the problem of
      proteases.
AB  - Homologous and heterologous protein production by filamentous fungi is often
      limited by the expression of proteases at high levels. By eliminating specific
      protease activities, protein production in Aspergillus niger can be improved
      considerably. Both classical mutagenesis and gene disruption techniques have
      yielded strains with reduced protease expression. Combinations of these mutations
      and disruptions result in a further reduction of protease activity. The coupling
      of efficient promoters to target genes allows their expression under conditions
      that repress the expression of several proteases, which further improves product
      yields. The strategies used have led to the development of a set of tester
      strains from which the appropriate genetic background for production can be
      selected.

PMID- 9237406
TI  - Probiotic properties of lactic-acid bacteria: plenty of scope for fundamental R &
      D.
AB  - Probiotic products are marketed widely throughout the world. This is especially
      true of yogurts that contain strains of lactic-acid bacteria of intestinal
      origin. Consumption of these products is aimed at promoting the wellbeing of the
      consumer by impacting on the collection of microorganisms that normally inhabit
      the intestinal tract. The development of scientifically valid probiotics requires
      more detailed knowledge of this intestinal microflora than is currently
      available.

PMID- 9237407
TI  - Oral narcotic protocol to reduce narcotic injections in refractory migraine
      patients.
AB  - Refractory headache patients who require narcotic injections for acute attacks
      frequently utilize health care facilities. The experience is often unpleasant and
      costly to the patient and health care system. We have developed an oral narcotic
      protocol for home administration. The patient starts with an antiemetic
      suppository, followed in 30 minutes by oral metoclopramide. After controlling
      nausea and vomiting, the patient administers a high dose of oral narcotic plus a
      hypnotic. The dosing of the narcotic analgesics incorporates seldom-used, but
      well-published pharmacokinetics. This protocol allows the patient to successfully
      treat a severe headache without using a health care facility. Eleven patients in
      our practice were prescribed the oral narcotic protocol. Their need for narcotic
      injections at our office or emergency department was monitored for up to 1 year
      before and after the start of the protocol. Combined office visits were reduced
      from 81 to 53 (34.6%) and emergency department visits from 47 to 26 (44.7%). An
      annual cost savings of $1960 for office visits and $3024 for emergency department
      visits was realized. This was offset by an oral narcotic protocol medication cost
      of only $392. This treatment method has been well accepted by patients and has
      proven to be a safe and cost-effective approach to treating refractory migraine
      patients.

PMID- 9237408
TI  - Trigeminal neuralgia. Clinical manifestations of first division involvement.
AB  - A series of 19 patients with what originally had been diagnosed as a first
      division (V1) trigeminal neuralgia was collected. The inclusion criteria were
      severe, rather short-lasting pain attacks within the V1 area, combined with
      trigger mechanisms. There were 10 women and 9 men, and the mean age of onset was
      57.8 years. Fifteen of 16 with adequate information on attack duration had
      paroxysms of a "few seconds" duration or less, whereas 10 patients had paroxysms
      lasting < or = 2 seconds. In an exceptional case, only "more long-lasting"
      attacks (greater than 30 seconds' duration) were experienced. In regard to
      autonomic phenomena, lacrimation was most frequently present (in a total of 8
      patients; 3 rather regularly, 5 more irregularly). The combination of
      lacrimation, conjunctival injection, and rhinorrhea was present in only 2 (of
      19), and in neither of them in a major way. Typically, autonomic phenomena
      occurred during the later stages of disease and during particularly severe and
      long-lasting attacks. Seven of 14 with adequate information also had nocturnal
      attacks. Initially, a more or less complete carbamazepine effect was reported by
      10 of 13 patients. Precipitation mechanisms were the same as with second and
      third division tic, but were mainly located within the V1 area, particularly
      initially. A comparison with SUNCT syndrome has been made. SUNCT is a
      predominantly male disorder, with only exceptional attacks of < or = 10 seconds'
      duration, and generally with attacks of 15 seconds or longer. Autonomic symptoms
      and signs are more pronounced than in V1 tic. Carbamazepine generally provides
      minor, if any, benefit in SUNCT. The present work strongly indicates that the two
      disorders are essentially different.

PMID- 9237409
TI  - Sympathetic vasoconstrictor outflow to extremity muscles in cluster headache.
      Recordings during spontaneous and nitroglycerin-induced attacks.
AB  - To search for evidence of sympathetic dysregulation during cluster headache
      attacks, microneurographic recordings of muscle nerve sympathetic activity (MSA)
      were obtained from the peroneal nerve. In three recordings commenced after the
      onset of spontaneous attacks, MSA was about twice as high during the attack as
      afterwards. In four nitroglycerin-induced attacks, MSA showed a rise paralleling
      the pain, preceded by an initial peak. The latter accompanied hypotension,
      whereas the rise coinciding with cluster headache was associated with rising
      blood pressure. The normal baroreflex-governed pulse synchrony of MSA was
      preserved both during spontaneous and provoked attacks. In seven cluster headache
      patients in whom nitroglycerin did not cause an attack, only an initial peak in
      MSA occurred. Nor was any late nitroglycerin-induced rise in MSA observed in nine
      healthy subjects; the initial peak in MSA and heart rate was followed by a rapid
      return to normal despite a falling blood pressure. It is concluded that cluster
      headache attacks are associated with an increase in MSA that elevates blood
      pressure by causing vasoconstriction, and that this increase, rather than
      indicating sympathetic dysregulation, is a normal pain-evoked secondary
      phenomenon. The findings in healthy subjects support the notion that
      nitroglycerin has a central sympatho-inhibitory effect.

PMID- 9237410
TI  - Pericranial muscle tenderness and exteroceptive suppression of temporalis muscle
      activity: a blind study of chronic tension-type headache.
AB  - The aim of the present study was to examine the ability of pericranial muscle
      tenderness and the second exteroceptive suppression period to distinguish chronic
      tension-type headache sufferers, migraine sufferers, and controls in a young
      adult population utilizing a blind design. The second exteroceptive suppression
      periods were assessed using the methodology recommended by the European Headache
      Federation and were scored with an automated computer software program designed
      in our laboratory to provide reliable, standardized, and precise quantification
      of exteroceptive suppression periods and eliminate any influence of experimenter
      bias that may occur with manual scoring. Our sample consisted of 45 subjects
      diagnosed according to IHS criteria: 25 with chronic tension-type headache and 20
      with migraine without aura. Twenty-three headache-free controls were recruited.
      Consistent with our previous findings, abnormalities in pericranial muscle
      tenderness, but not in the second exteroceptive suppression period distinguished
      chronic tension-type headache sufferers from controls. The chronic tension
      headache sufferers exhibited the highest pericranial muscle tenderness and the
      control group exhibited the lowest tenderness (P < .001). Pericranial muscle
      tenderness was quite successful in distinguishing recurrent headache sufferers
      from controls, but failed to distinguish chronic tension-type headache sufferers
      from migraineurs. Our findings raise the possibility that pericranial muscle
      tenderness is present early in the development of chronic tension-type headache
      and migraine without aura, and thus might contribute to the etiology of headache
      disorders. Our findings also indicate that a shortened second exteroceptive
      suppression period is not a reliable marker for chronic tension-type headache in
      young adults.

PMID- 9237411
TI  - Droperidol treatment of status migrainosus and refractory migraine.
AB  - We conducted a pilot study of intravenous droperidol in 35 patients (32 women and
      3 men; mean age 43 years) with status migrainosus (n = 25) or refractory migraine
      (n = 10) in an ambulatory infusion center. Headache was graded as severe in 21
      patients and moderate in 14. An intravenous line was started and kept open.
      Droperidol (2.5 mg) was given intravenously every 30 minutes until either three
      doses were given or the patient was completely or almost headache-free prior to
      the next dose. Seven patients received one dose, 12 received two doses, and 16,
      three doses (mean 5.6 mg). Our success rate (headache-free or mild headache) was
      88% (22 of 25) in patients with status migrainosus and 100% (10 of 10) in
      patients with refractory migraine. The average time to headache improvement was
      40 minutes (n = 35), to mild headache--60 minutes (n = 32), and to headache-free-
      105 minutes (n = 28). Nausea, vomiting, and light and sound sensitivity resolved
      in all but 5 patients. Four patients had an asymptomatic systolic blood pressure
      drop > or = 20 mm Hg. Most patients were sedated (34 of 35). Five patients
      developed akathisia and 1 dystonia. At follow-up 24 hours after discharge, the
      recurrence rate (headache intensity from none or mild to moderate or severe) was
      23% in status migrainosus and 10% in refractory migraine. Twenty-one patients
      were sedated, while 19 had extrapyramidal symptoms, mainly restlessness.
      Droperidol is effective and safe in treating status migrainosus or refractory
      migraine. Hypotension was uncommon. Patients should be warned of sedation and
      akathisia.

PMID- 9237412
TI  - Visual evoked potentials and serum magnesium levels in juvenile migraine
      patients.
AB  - Changes in visual evoked potentials and decreased intracellular magnesium levels
      have been separately described in patients affected by migraine both during the
      attacks and in the interictal periods. An inverse correlation between increased
      P100 amplitude and lowered serum magnesium levels was found in children suffering
      from migraine with and without aura in a headache-free period. A 20-day treatment
      with oral magnesium pidolate seemed to normalize the magnesium balance in 90% of
      patients. After treatment, the reduced P100 amplitude confirmed the inverse
      correlation with the serum magnesium level. These data seem to suggest the
      hypothesis that higher visual evoked potential amplitude and low brain magnesium
      level can both be an expression of neuronal hyperexcitability of the visual
      pathways related to a lowered threshold for migraine attacks.

PMID- 9237413
TI  - Headache and stress in a group of nurses and government administrators in Japan.
AB  - We surveyed a group of 311 nurses and 283 mid-level government administrators in
      Yamagata Prefecture, Japan, to determine the prevalence and character of their
      headaches. We investigated the relationship of headaches to the subjects' stress,
      and their behavior and coping patterns. The questionnaire we administered
      explored background factors, as well as the state of the respondents' mental
      health, life events, work motivation, support system, and interpersonal
      relationships. The questionnaire was completed by 76.8% of nurses and 100% of
      administrators. Of these, 40.6% of nurses and 19.1% of the administrators
      reported recurrent headaches. Furthermore, the number of headache sufferers among
      the women administrators was significantly higher than in the men. The nurses and
      the administrators who reported headache scored significantly higher than the
      nonheadache groups on the questions measuring symptoms of burnout, General Health
      Questionnaire, and learned helplessness. The group of nurses with headache had
      higher scores for life events, decreased work motivation, and nervous behavior
      than the nonheadache group; the administrators with headache scored higher for
      daily hassles than those of the nonheadache groups. In this study of a Japanese
      sample, the character of the subjects' headache and the possible inducing factors
      are consistent with those reported in studies of Europeans and Americans using
      similar testing methods. However, the high prevalence of headache among nurses
      and women administrators seems to be related to psychological stress,
      particularly work stress, which may be characteristic in Japan.

PMID- 9237414
TI  - Sumatriptan relieves migrainelike headaches associated with carbon monoxide
      exposure.
AB  - We report a 58-year-old woman with long-standing migraine who developed a pattern
      of weekend headaches which occurred only while staying at her Connecticut
      vacation home. The headaches promptly responded to sumatriptan. Investigation
      revealed a high carbon monoxide level in her home due to a defective furnace.
      Replacing the furnace eliminated the headaches. This case highlights the
      importance of searching for secondary causes of headache even in patients
      responsive to sumatriptan. It also suggests that carbon monoxide may trigger
      headaches mediated by trigeminovascular inflammation.

PMID- 9237415
TI  - Recurrent branch retinal infarcts in association with migraine.
AB  - Migraine has been blamed for a variety of temporary and permanent visual
      complications. We describe the case of a young woman with migraine who suffered
      recurrent episodes of retinal infarction, one of which occurred during an attack
      of migraine. The infarctions resulted from occlusions of branches of the central
      retinal artery. Extensive laboratory and radiological investigations failed to
      establish a nonmigrainous etiology. In some individuals, migraine may cause or
      promote branch retinal vaso-occlusion and infarction.

PMID- 9237416
TI  - Saccular aneurysm of the external jugular vein, an unusual cause of neck
      swelling.
AB  - Enlargement of neck swelling on Valsalva maneuver raises the diagnosis of
      laryngocele or jugular aneurysm. When considering this latter type of lesion,
      though fusiform cervical venous aneurysms represent a frequent occurrence,
      sacciform aneurysms are much rarer. We report two exceptional cases of saccular
      aneurysms of the external jugular vein which presenting symptom was a neck lump
      that enlarged on Valsalva maneuver. Although computed tomography and selective
      venography allow accurate diagnosis, ultrasonography with color flow duplex
      imaging is the gold standard for the diagnosis of such venous aneurysms of the
      neck.

PMID- 9237417
TI  - A patient with congenital short small bowel associated with malrotation.
AB  - A case of congenital short small bowel associated with malrotation and
      malabsorption in a baby girl is presented. Clinical manifestations developed in
      the first days after birth and consisted of diarrhea, vomiting and poor weight
      increase. Congenital short small bowel was suspected on radiological examination,
      which showed an associated malrotation. The diagnosis was confirmed by
      exploratory laparotomy. The length of the small intestine was only 50 cm. The
      intensive work of maintaining nutrition and controlling infection is described.

PMID- 9237418
TI  - Ultrasound examination of the wrist.
AB  - Ultrasonography of the wrist requires knowledge of the normal anatomy and
      dedicated ultrasound equipment. The patient's complaints orientate the
      examination. Real time dynamic examination provides essential information. In
      tendon pathology, ultrasound demonstrates better than MRI partial rupture,
      different types of synovitis and nodular deposits such as tophi, amyloid or
      pannus. In opposition to ganglion cysts, a joint communication is seen in
      arthrosynovial cysts. In carpal tunnel syndrome, the surface of the median nerve
      exceeds 15 sqmm. Ultrasound can demonstrate in specific cases traumatic lesions
      of bony surfaces or lesions of the triangular fibro-cartilage.

PMID- 9237420
TI  - Lesion detection in breast carcinoma.
AB  - Early detection and identification of infraclinic breast lesions are a challenge
      for the radiologist. Diagnostic accuracy relies on careful analysis of some
      important mammographic clues, which are discussed in this paper. In particular,
      asymmetric breast tissue, focal asymmetric density, nonpalpable solid masses,
      stellate lesions and calcifications are reviewed.

PMID- 9237419
TI  - Imaging findings in patients with failed back surgery syndrome.
AB  - The incidence of low back pain and leg pain related to the spine is very high in
      the Western population. As a result of conservative treatment failure there are
      roughly 200,000 lumbar disk operations performed annually. Unsuccessful surgical
      outcome is known as the failed back surgery syndrome (FBSS). FBSS is a complex
      and poorly understood syndrome, with as many different imaging findings as
      different possible etiologic mechanisms. Still we believe some imaging aspects
      deserve special attention. Firstly it is of particular importance to correctly
      differentiate residual disk herniation from epidural scar tissue since disk
      herniation can be an indication for repeat intervention. Secondly when residual
      disk herniation is present, one should keep in mind that it is not necessarily
      responsible for the patients complaints. Thirdly, late nerve root enhancement
      should be considered as pathological. Finally one should be aware of the
      mechanical back stress that may develop as a result of discectomy. One of the
      consequences can be secondary foraminal stenosis which is probably one of the
      most common causes of FBSS.

PMID- 9237421
TI  - Nasal and paranasal sinus imaging.
AB  - Functional endoscopic sinus surgery has become the surgical treatment of choice
      in many patients with inflammatory sinus disease refractory to medical treatment.
      Coronal CT scanning is the imaging modality of choice as it provides initial
      screening, contributes to surgical planning, and provides an operative "roadmap".
      The authors stress that close cooperation between the radiologist and the surgeon
      is mandatory both for evaluation and treatment of paranasal disorders.

PMID- 9237422
TI  - Synthesis of 2-oxacortexone and its effect on Ca2+ uptake in bovine spermatozoa.
AB  - Low temperature base catalyzed autoxidation (BCA) of the A-ring of 21
      acetoxypregn-5-ene-3,20-dione 20-ethylene ketal (7) resulted in the
      saponification of the ester with the concomitant formation of 2,21
      dihydroxypregna-1,4-diene-3,20-dione 20-ethylene ketal (8). Continued BCA at
      ambient temperature, converts the latter to 1,21-dihydroxy-2-oxaprogesterone 20
      ethylene ketal (9), which is reduced by NaBH4 to the 2-oxasteroid, 21-hydroxy-2
      oxaprogesterone 20-ethylene ketal (10). Treatment of enol 8, lactol 9, and
      lactone 10 with aqueous acid generates the corresponding deprotected analogs 2,21
      dihydroxypregna-1,4-diene-3,20-dione (enol 11), 1,21-dihydroxy-2-oxaprogesterone
      (lactol 12), and 2-oxacortexone (2-oxadesoxycorticosterone, 21-hydroxy-2
      oxaprogesterone, lactone 13). In bovine spermatozoa, neither 2-oxasteroid ketal
      10 nor its deprotected analog 13 stimulated Ca2+ uptake. In high concentration
      (0.5 mM), the inhibition of Ca2+ uptake is only 37% for 13, as compared to 83%
      found with the parent steroid, cortexone (desoxycorticosterone, 21
      hydroxyprogesterone, 5). The difference in molecular structure between 13 and 5
      indicates the importance of the oxygen atom in ring A in achieving the protective
      effect of the steroid. Ketalization of the C-20 carbonyl is not important for
      protection. Thus it seems that by replacing C-2 by an oxygen atom we can reduce
      the biological damage caused by relatively high concentrations of steroid
      treatment. These results are highly significant when treatment of patients with
      high doses of steroids is considered.

PMID- 9237423
TI  - SAR studies on the potent and selective muscarinic antagonist 2-ethylthio-2,2
      diphenylacetic acid N,N-diethylaminoethyl ester.
AB  - Molecular modification of the potent and selective muscarinic antagonist 2
      ethylthio-2,2-diphenylacetic acid N,N-diethylaminoethyl ester was performed in
      order to identify M2 selective antagonists able to cross the blood brain barrier
      and potentially useful in the treatment of Alzheimer's disease. Modifications
      included substitution or hydrogenation of one of the phenyl rings as well as
      their incorporation in a tricyclic system. In general the changes introduced were
      detrimental for both affinity and selectivity. Only a modest M2 selectivity is
      present in some compounds that, on the other hand, carry a quaternary ammonium
      group which precludes their penetration into the brain.

PMID- 9237424
TI  - Synthesis and biological evaluation of a series of quinazoline-2-carboxylic acids
      and quinazoline-2,4-diones as glycine-NMDA antagonists: a pharmacophore model
      based approach.
AB  - The synthesis and glycine-NMDA binding activity of a series of quinazoline-2
      carboxylic acids 1 and quinazoline-2,4-diones 2, containing all the essential and
      optional pharmacophoric descriptors required by a putative glycine antagonist
      model, are reported. The binding results show that only three of the title
      compounds displayed micromolar receptor affinity, demonstrating how disappointing
      the synthesis of receptor ligands based only on interaction models can be.

PMID- 9237425
TI  - Influence of various estrogens on biotransformation: affinity to cytochrome P
      450, structure activity relationships, and scavenger function.
AB  - Nine natural and synthetic estrogens all derived from endogenous 17 beta
      estradiol, were tested for their affinity to cytochrome P-450 (P450). Binding
      spectra of the estrogens with rat liver microsomal P450 and inhibition kinetics
      with characteristic monooxygenase model reactions (ethylmorphine N-demethylation,
      EN, and ethoxycoumarin O-deethylation, EO) were determined. In addition,
      uncoupling effects and/or free radical scavenger functions were analysed by
      NADPH/Fe2+ stimulated microsomal luminol- and lucigenin-amplified
      chemiluminescense (CL). 17 beta-Estradiol, 17 alpha-ethynylestradiol, and D
      estradiol 3-methyl ether inhibited both monooxygenase reactions of cytochrome P
      450, whereas L-estradiol 3-methyl ether inhibited EO only. 17 beta-Estradiol, 17
      alpha-ethynylestradiol, and D-estradiol 3-methyl ether seem to act as free
      radical scavengers. From the results both structure activity relationships could
      be established and data on possible interferences with drug metabolism obtained.
      The enantiomers D- and L-estradiol 3-methyl ether differ in their effects on
      these systems.

PMID- 9237426
TI  - Synthesis and in vitro evaluation of 3-(1-azolylmethyl)-1H-indoles and 3-(1
      azolyl-1-phenylmethyl)-1H-indoles as inhibitors of P450 arom.
AB  - In the challenge to develop potent inhibitors of aromatase for reducing the
      levels of estrogens, we found that azolyl-substituted indoles inhibit aromatase
      activity, 3-(1-Azolylmethyl)-1H-indoles 9-15 and 3-(1-azolyl-1-phenylmethyl)-1H
      indoles 22-25 were prepared, and tested on their ability to inhibit P450 arom.
      Analysis of the inhibitory effect exerted by several derivatives (11, 12, 22, and
      23) on microsomal aromatase in vitro activity indicates that azolyl-substituted
      indoles containing an imidazole moiety are more potent inhibitors than triazole
      derivatives. In the first series, the introduction of the N-benzyl moiety has
      been found to enhance the inhibitory profile of these 3-(1-azolylmethyl)-1H
      indole derivatives. The corresponding 4-fluoro derivative 12 displays the highest
      inhibitory activity (IC50 = 0.0718 microM) of all investigated compounds; thus,
      12 is 258 times as potent as aminoglutethimide (AG). The presence of a chloro
      grouping in para position of the phenyl ring in compounds 22 and 24 exerts a
      positive effect only in the triazol-l-yl sub-series: compound 25 is 4-fold more
      potent than 24.

PMID- 9237427
TI  - Conformational flexibility of serotonin1A receptor ligands from crystallographic
      data. Updated model of the receptor pharmacophore.
AB  - Preparation and affinity to 5-HT1A and 5-HT2A receptors of new buspirone
      analogues 7-17 are reported. The compounds possess high to low affinity to 5-HT1A
      and moderate to low to 5-HT2A receptors. The crystal structures have been
      determined for compounds 11, 12, 13, and 14. For low affinity ligand (15) of 5
      HT1A receptor conformational analysis was performed and compared with similar
      analyses performed for know high (buspirone 1) and very high (WY-48,723 2)
      affinity ligands of the receptor. Structure-activity relationship is discussed
      for the affinity to 5-HT1A receptor. A three-point pharmacophore explaining
      interactions of buspirone-like molecules with the receptor binding site is
      proposed.

PMID- 9237428
TI  - 1997: centenary of the synapse.

PMID- 9237429
TI  - The archaeological attributes of behaviour: difference or variability?
AB  - Did the Neanderthals evolve into anatomically modern humans, or were they
      replaced by incoming populations of Homo sapiens sapiens? This is perhaps the
      most well-known question debated by palaeoanthropologists and archaeologists
      interested in the period from roughly 250,000 to 30,000 years ago in Eurasia. But
      while this debate may have attracted most of the media attention, there are other
      research questions that are at least as worthy of public interest as biological
      origins.

PMID- 9237430
TI  - The quest by three giants of science for an understanding of cancer.
AB  - Understanding the causes of cancer remains a major area of uncertainty, and many
      serious proposals have been made from a variety of standpoints over the years.
      This article discusses the first genetic hypothesis from the turn of the century
      and two other totally different early approaches to the problem.

PMID- 9237431
TI  - The 'internal clocks' of circadian and interval timing.
AB  - Animals engage in a startlingly diverse array of behaviours that depend
      critically on the time of day or the ability to time short intervals. Timing
      intervals on the scale of many hours to around a day is mediated by the circadian
      timing system, while in the range of seconds to hours a different system, known
      as interval timing, is used. Recent research has illuminated some of the neural
      mechanisms underlying the 'internal clocks' of these two different timing systems
      in both animals and humans. Therapeutic applications for humans with impairments
      in either timing system may ultimately result from these endeavours.

PMID- 9237432
TI  - Diagnostic value of three-dimensional transcranial contrast duplex sonography.
AB  - This study evaluated intracranial cerebral arteries using a new data acquisition
      system for transcranial three-dimensional (3D) ultrasonography with and without
      an echo contrast agent, with confirmation by cerebral angiography. Ten patients,
      studied with diagnostic cerebral angiography, were examined without knowledge of
      the angiographic results. Data acquisition through the transtemporal acoustic
      window was performed using a magnetic sensor system to track the spatial
      orientation of the ultrasound probe while scanning the volume of interest. A
      color transcranial duplex system with a power Doppler mode was used, and 3D data
      sets were acquired before and after the injection of transpulmonary-stable
      ultrasound contrast medium. Ipsilateral to the transducer, the anterior cerebral
      artery (ACA) in 90%, middle cerebral artery (MCA) in 60%, all three or more
      branches of the MCA in 60%, posterior cerebral artery (PCA) in 60%, and posterior
      communicating artery (PCoA) in 60% were successfully imaged without the echo
      contrast agent. With the contrast agent, the ACA, MCA, three or more branches of
      the MCA, PCA, and PCoA were visible in 100%. The anterior communicating artery
      was visualized in 40% without contrast enhancement and in 90% with contrast
      enhancement. Contralateral to the transducer, the ACA (60%), MCA (30%), all three
      or more branches of the MCA (10%), PCA (20%), and PCoA (20%) were successfully
      imaged without contrast. Contrast enhancement improved the imaging success rate
      for the ACA (90%), MCA (80%), three or more branches of the MCA (80%), PCA
      (100%), and PCoA (100%). A transpulmonary-stable ultrasound contrast agent used
      in combination with 3D transcranial duplex ultrasonography can significantly
      improve the success rate for transcranial color duplex imaging of intracranial
      arteries.

PMID- 9237433
TI  - Self-paced versus metronome-paced finger movements. A positron emission
      tomography study.
AB  - To evaluate the hypothesis that self-paced movements are mediated primarily by
      the supplementary motor area, whereas externally triggered movements are mainly
      affected by the lateral premotor cortex, different movements in 6 healthy
      volunteers were studied while changes in regional cerebral blood flow (rCBF) were
      measured using positron emission tomography (PET) and 15O-labeled water. Subjects
      made a series of finger opposition movements initiated in a self-paced manner
      every 4 to 6 seconds, and separately, made continuous finger opposition movements
      at a frequency of 2 Hz paced by a metronome. The primary motor cortex, lateral
      area 6, cerebellum on both sides, and caudal cingulate motor area, and the
      putamen and thalamus on the contralateral side were more active during the
      metronome-paced movements. The increases in rCBF in these areas are likely the
      result of the larger number of movements per minute made with the externally
      triggered task. The anterior supplementary motor area and rostral cingulate motor
      area in the midline, prefrontal cortices bilaterally, and lobus parietalis
      inferior on the ipsilateral side were more active during the self-paced
      movements. Increases in rCBF in those areas, which include medial premotor
      structures, may be related to the increased time devoted to planning the movement
      in this condition.

PMID- 9237434
TI  - Vasodilatory responses and magnetic resonance angiography. Extracranial and
      intracranial intravascular flow data.
AB  - This study measured the responses of both extracranial (internal carotid
      arteries) and intracranial (middle cerebral/angular, basilar arteries)
      intravascular arterial volume flow rates to acetazolamide using phase-contrast
      magnetic resonance angiography. Twenty-eight newly studied patients were
      subdivided into four groups: Group I--Nonocclusive, asymptomatic (n = 7, or 14
      carotid and middle cerebral/angular artery sides); Group II--unilateral carotid
      transient ischemic attacks, nonhemodynamic (embolic), varying stenoses (n = 11);
      Group III--unilateral carotid transient ischemic attacks, hemodynamic, varying
      stenoses (n = 5); and Group IV--unilateral carotid occlusion, asymptomatic (n =
      5). The data were separated into nonischemic and ischemic sides so as to
      illustrate group differences based on vasodilatory responses to acetazolamide.
      For example, the percent change in volume flow rates over baseline values for the
      ischemic-side middle cerebral arteries of Group III was significantly the lowest
      of all of the vasodilatory responses (-25 +/- 11% vs 40 +/- 14% for group II
      ischemic middle cerebral/angular artery sides, p = 0.008). Group III patients
      also had significantly lower standing blood pressures (p = 0.012), higher number
      of transient ischemic attacks (p = 0.008), and shorter duration of events (p =
      0.013). Determinations of volume flow rate continue to assist in determining the
      degree of hemodynamic compromise of a particular vascular territory.

PMID- 9237436
TI  - Using transcranial duplex sonography for monitoring vessel patency during surgery
      for intracranial aneurysms.
AB  - This article reports a method for reliable intraoperative monitoring of blood
      flow velocities in the basal cerebral arteries during clipping of intracerebral
      aneurysms. Transcranial color-coded duplex sonography provides practical
      integration of transcranial Doppler technology with real-time imaging
      capabilities through the intact human skull. With a computerized sonography
      system equipped with a 2.5-MHz probe in 50 healthy volunteers, the contralateral
      internal carotid artery, A1 and A2, as well as M1 and P1 vessels were identified
      and measured in most patients. In 13 patients undergoing dipping of intracranial
      aneurysms, the technique successfully imaged 12; it allowed definitive
      identification of vessels potentially threatened by clipping and not fully
      visible to the surgeon. Data were easily comparable to preoperative data. This
      noninvasive, repeatable neuroimaging technique provides useful intraoperative
      information about intracranial hemodynamics during dipping of intracranial
      aneurysms.

PMID- 9237435
TI  - Optimized transcranial Doppler technique for the diagnosis of cardiac right-to
      left shunts.
AB  - Transcranial Doppler sonography (TCD) is a simple method to detect a right-to
      left cardiac shunt, although standardized procedures do not exist. In this study
      69 patients were tested according to predetermined criteria and procedures
      (cluster of > 10 microbubbles, duration between injection in the cubital vein and
      detection in the middle cerebral artery [MCA] < or = 10 sec). Agitated saline
      solution was compared to oxypolygelatine, a plasma volume expander, as contrast
      media. Valsalva's maneuver and coughing were used to provoke right-to-left
      cardiac shunting, detected by TCD, transthoracic echocardiography (TTE), and
      transesophageal echocardiography (TEE). Oxypolygelatine caused a significantly
      higher number of microbubbles in the right atrium and MCA than did the saline
      solution, leading to a greater diagnostic reliability of TCD (paired t test, p <
      0.001). Coughing did not provoke right-to-left cardiac shunts (x2 analysis, p <
      0.001). The technique used for carrying out Valsalva's maneuver was important for
      the detection of right-to-left cardiac shunts. Twenty-five right-to-left shunts
      were diagnosed with TCD and 18 with TTE (36 vs 26%; x2 analysis, p = 0.1). The
      findings indicate that TCD when properly done is highly sensitive and specific
      for the diagnosis of right-to-left cardiac shunts.

PMID- 9237437
TI  - A 66-year-old woman with a rapidly progressing dementia and basal ganglia
      involvement.
AB  - A 66-year-old woman presented with a rapidly progressive dementia initially
      characterized by an auditory agnosia. She experienced a rapid progression of her
      aphasia and developed ataxia and myoclonus. An initial neurological evaluation
      suggested a left parieto-temporal lesion, however, neuroimaging did not reveal
      any. An MRI of her brain demonstrated highly focal T2 hyperintensities in her
      basal ganglia. The patient was diagnosed with Creutzfeldt-Jacob Disease (CJD) on
      the basis of the presence of two proteins in the CSF that are highly sensitive
      and specific for CJD. Pathological examination confirmed the diagnosis. The
      differential diagnosis and utility of MRI in patients with CJD is discussed.

PMID- 9237438
TI  - Fast inversion recovery for myelin suppression (FIRMS). A new magnetic resonance
      pulse sequence.
AB  - Fast inversion recovery for myelin suppression is a new magnetic resonance
      sequence with the ability to increase gray-white matter contrast. This can
      improve the definition of normal anatomical structures.

PMID- 9237439
TI  - An approach to imaging the dizzy patient.
AB  - Disease of the vestibular system involves a lengthy differential diagnosis, from
      the relatively trivial to potentially life-threatening conditions. As a
      definitive specific diagnosis is often difficult to make, imaging may be used
      simply to "rule out" serious pathology. In this context, suboptimal imaging
      choices may be unnecessarily expensive and may fail to document the pathology. In
      contrast, an orderly investigation includes appropriate audiometric and
      vestibular tests, which when reviewed in the clinical context, indicate the most
      pertinent imaging modalities. This enables the clinician to plan a cost
      effective, definitive imaging strategy. This review considers the role of imaging
      in an integrated approach to investigating the dizzy patient. A discussion of
      vestibular pathology is presented to assist in the review, and several cases are
      provided as examples.

PMID- 9237440
TI  - Stenting: a new approach to carotid dissection.
AB  - A patient with bilaterally occluded internal carotid arteries had a right
      hemispheric stroke followed by a left cerebral infarction, secondary to
      dissection from fibromuscular dysplasia, seen also in the vertebral arteries. The
      occluded left carotid was reopened and stents placed, with apparent
      reestablishment of left hemispheric blood flow. The speech and other deficits
      resolved. Although its use is under investigation, percutaneous balloon
      angioplasty with stents may be an appropriate intervention when other measures do
      not prevent progressive ischemic events.

PMID- 9237441
TI  - Transcranial power-mode duplex ultrasound in two patients with moyamoya syndrome.
AB  - Moyamoya syndrome is characterized by the reticulated collateralization of the
      intracranial vasculature distal to an occlusion of proximal intracranial vessels.
      In the present study this pathology was visualized in 2 patients, aged 29 and 32
      years, using transcranial color Doppler imaging (TCDI). Digital subtraction
      angiography in both patients revealed stenosis of the intracranial portion of the
      internal carotid arteries, occlusion and stenosis of several cerebral arteries,
      and a bilateral reticulated collateral network particularly in the region of both
      basal ganglia, typical of moyamoya syndrome. TCDI with power-mode Doppler
      depicted parts of the intracranial collateral network, not possible using
      conventional color-flow Doppler. TCDI with power-mode Doppler permitted better
      visualization of intracranial vascular pathology in comparison to conventional
      color-flow Doppler, enabling a rapid and noninvasive diagnosis of rare
      cerebrovascular anomalies.

PMID- 9237442
TI  - Fluctuating MRI findings in a patient with central nervous system idiopathic
      hypereosinophilic syndrome: a case report.
AB  - Central nervous system involvement in the idiopathic hypereosinophilic syndrome
      is well recognized and is probably the result of an eosinophilic-derived
      neurotoxin. This report documents evanescent magnetic resonance imaging findings
      correlating with active central nervous system disease and subsequent treatment
      effects.

PMID- 9237443
TI  - Central nervous system lesions associated with Crohn's disease.
AB  - Central nervous system vasculitis is an exceptional extraintestinal manifestation
      of Crohn's disease. Reported here are 2 cases, highlighting the difficulty of
      differential-diagnosis with multiple sclerosis and stressing the importance of
      early immuno-suppressive therapy.

PMID- 9237444
TI  - Transcranial duplex sonography of hyperacute intracerebral hemorrhages.

PMID- 9237445
TI  - Brain-mapping neurotoxicity and neuropathology.

PMID- 9237446
TI  - Classical and contemporary histochemical approaches for evaluating central
      nervous system microanatomy.

PMID- 9237447
TI  - Assessment of neurotoxicity from potential medications for drug abuse: ibogaine
      testing and brain imaging.
AB  - New technologies utilized for monitoring brain function can be more sensitive in
      the assessment of desired or undesired pharmacological effects than can clinical
      examination. Nonetheless, careful case-by-case analysis is required to determine
      to what extent a change detected with a sensitive imaging modality will have
      clinical significance. Whereas in some instances the technology may suggest a
      subclinical condition years before clinical signs develop, in other instances
      changes seen may be compensated for through system reserves, redundancy, or
      plasticity. Furthermore, simultaneous application of several assay instruments,
      including behavioral, electrophysiological, and nuclear medicine approaches, may
      be appropriate and useful for establishing correlations between changes in
      specific aspects of brain function and amelioration of a disease (drug abuse
      disorder) or its sequelae. In the example of ibogaine, a testing strategy was
      developed to assess human subjects for possible changes in cerebellar function
      (that were suggested by preclinical findings indicating subtle damage). Thus,
      subjects may be tested for subclinical alterations during and immediately
      following a clinical trial. This "harbinger of toxicity" approach would provide
      clinicians the critical data necessary for appropriate follow-up of subjects as
      well as the propriety of continuance of the clinical trials within the ibogaine
      project.

PMID- 9237448
TI  - Imaging studies of cocaine in the human brain and studies of the cocaine addict.

PMID- 9237449
TI  - In vivo imaging of fatty acid incorporation into brain to examine signal
      transduction and neuroplasticity involving phospholipids.
AB  - An in vivo method is presented that allows quantification and imaging of fatty
      acid incorporation into different brain phospholipids in relation to membrane
      synthesis, neuroplasticity, and signal transduction. The method can be used with
      positron emission tomography, and may help to evaluate brain phospholipid
      metabolism in humans with brain tumors, neurodegenerative disease, cerebral
      ischemia or trauma, or neurotoxic effects of drugs or other agents.

PMID- 9237450
TI  - Magnetic resonance spectroscopy and spectroscopic imaging for the study of brain
      metabolism.

PMID- 9237451
TI  - Multiecho approaches to spectroscopic imaging of the brain.
AB  - Spectroscopic imaging (SI) with nuclear magnetic resonance (NMR) is one of the
      most powerful tools available for studying brain chemistry in vivo. Both proton
      (1H) and phosphorus (31P) NMR offer valuable biochemical information that can in
      principle be mapped throughout the entire brain, thereby enhancing our
      understanding of brain function. With the exception of protons from tissue water
      and the triglycerides of adipose tissue, however, nuclei contributing to the NMR
      signals of living tissue are in relatively small (millimolar) concentrations. The
      low concentration of metabolite nuclei reduces the overall sensitivity of
      conventional SI techniques, making high-quality metabolite mapping a lengthy
      procedure. This problem has led to the development and testing of nonconventional
      methods for reducing SI scan times, including techniques based on the collection
      of multiple spin-echoes. The extent to which multiecho methods can be used to
      decrease SI scan times and maintain high-quality metabolite mapping depends on
      several factors. These include the spectral transverse relaxation times, the
      spectral resolution required, and J-coupling interactions. We have discussed
      these various technical aspects of multiecho SI methods as applied to 1H and 31P
      spectroscopic imaging of the living brain.

PMID- 9237452
TI  - New histological and physiological stains derived from diffusion-tensor MR
      images.

PMID- 9237453
TI  - Magnetic resonance microscopy in basic studies of brain structure and function.

PMID- 9237455
TI  - Strategies of visual perception suggested by optically imaged patterns of
      functional architecture in monkey visual cortex.

PMID- 9237454
TI  - Near-infrared imaging and spectroscopy in stroke research: lipoprotein
      distribution and disease.

PMID- 9237456
TI  - Near-field scanning optical microscopy and near-field confocal optical
      spectroscopy: emerging techniques in biology.

PMID- 9237457
TI  - Automated light microscopy for the study of the brain: cellular and molecular
      dynamics, development, and tumorigenesis.

PMID- 9237458
TI  - Using emerging technologies such as virtual reality and the World Wide Web to
      contribute to a richer understanding of the brain.

PMID- 9237459
TI  - Applications of fourier transform infrared imaging microscopy in neurotoxicity.

PMID- 9237460
TI  - Advances in optical imaging of biomedical media.
AB  - In this article, we have presented an overview of fundamental issues involved in
      mediphotonic imaging, and reviewed some of the emerging techniques for early
      light transillumination imaging of body organs. The results on human breast
      tissues presented here, together with the data accumulated and advances made by
      researchers around the globe, not only demonstrate the feasibility of optical
      imaging as a clinical procedure but indicate a road map to reach that goal. The
      milestones include evaluation of relative merits of available approaches for a
      particular imaging application; selection of diagnostic wavelengths, as well as
      sources to generate and detectors to monitor light at those wavelengths;
      accumulation of data on optical, spectroscopic, and transport properties of
      tissues and organs; in vivo testing; prototype instrumentation development;
      clinical trials; governmental approval; cost analysis and marketing; and finally
      system improvement based on feedback from end users. A new era of optical
      clinical imaging is at the door.

PMID- 9237461
TI  - Noninvasive detection of fast signals from the cortex using frequency-domain
      optical methods.

PMID- 9237462
TI  - Self-knowledge and self-awareness.

PMID- 9237463
TI  - The roots of self-knowledge: perceiving self, it, and thou.

PMID- 9237464
TI  - A comparison of the self-awareness and kinesthetic-visual matching theories of
      self-recognition: autistic children and others.

PMID- 9237465
TI  - What is mirror self-recognition in nonhuman primates, and what is it not?

PMID- 9237466
TI  - On the rise and fall of self-conception in primates.

PMID- 9237467
TI  - Self and self-control.

PMID- 9237468
TI  - Finding one's self in time.

PMID- 9237471
TI  - Culture and the self: uncovering the cultural grounding of psychological theory.

PMID- 9237470
TI  - The social construction of the remembered self: family recounting.

PMID- 9237469
TI  - The self in self-conscious emotions.
AB  - The study of self-conscious emotions has only recently begun. The model outlined
      here offers an opportunity to consider and to define carefully some of the self
      conscious emotions. Unless we develop a more accurate taxonomy, we will be unable
      to proceed in our study of these emotions. Given the renewed interest in
      emotional life, it is now appropriate to consider these more complex emotions
      rather than the more "primary" or "basic" ones. Moreover, as others have pointed
      out, these self-conscious emotions are intimately connected with other emotions,
      such as anger and sadness (see for example, H.B. Lewis, 1971; Lewis, 1992b;
      Morrison, 1989). Finally, given the place of self-evaluation in adult life, it
      seems clear that the self-conscious evaluative emotions are likely to stand in
      the center of our emotional life (Dweck & Leggett, 1988; Heckhausen, 1984).

PMID- 9237472
TI  - The self in relation to others: cognitive and motivational underpinnings.

PMID- 9237473
TI  - The development of a self. Comments on the paper of Neisser.

PMID- 9237474
TI  - The human self and the animal self: behavioral problems with few answers.
      Comments on the papers of Mitchell, Swartz, and Gallup.

PMID- 9237475
TI  - Status report on the Childhood Immunization Initiative: national, state, and
      urban area vaccination coverage levels among children aged 19-35 months--United
      States, 1996.
AB  - The Childhood Immunization Initiative (CII), a comprehensive response to under
      vaccination among preschool-aged children, was initiated in the United States in
      1993 (1). The CII established the goal of increasing vaccination coverage levels
      among children aged 2 years to > or = 90% by 1996 for the most critical doses of
      each vaccine routinely recommended for children (except hepatitis B vaccine, for
      which the objectives were to increase coverage to 70% by 1996 and 90% by 1998).
      This report presents final 1996 estimates of coverage with vaccines targeted by
      CII among children aged 19-35 months, which indicate that in 1996 all national
      vaccination coverage goals were exceeded for the routinely recommended vaccines.

PMID- 9237476
TI  - Status report on the Childhood Immunization Initiative: reported cases of
      selected vaccine-preventable diseases--United States, 1996.
AB  - The Childhood Immunization Initiative (CII), a comprehensive response to under
      vaccination among preschool-aged children, was initiated in the United States in
      1993 (1). The goals of the CII were to eliminate by 1996 indigenous cases of
      diphtheria, tetanus (among children aged < 15 years), poliomyelitis, Haemophilus
      influenzae type b (Hib) invasive disease (among children aged < 5 years),
      measles, and rubella (1); reduce indigenous cases of mumps to < 1600; and
      increase vaccination coverage levels to > or = 90% among children aged 2 years
      for the most critical doses of each vaccine routinely recommended for children
      (except hepatitis B vaccine). This report presents provisional 1996 data about
      reported cases of selected vaccine-preventable diseases. In 1996, no cases of
      tetanus among children aged < 15 years or of polio caused by wild poliovirus were
      reported in the United States; the number of reported cases of indigenously
      acquired mumps was substantially below the disease-reduction target; and the
      numbers of reported cases of diphtheria, invasive Hib disease (among children
      aged < 5 years), rubella, and measles were at or near the lowest levels ever
      recorded and near the elimination targets.

PMID- 9237477
TI  - Acute childhood leukemia--Columbus, Ohio.
AB  - From August-October 1975, 8 cases of acute leukemia were diagnosed at Columbus
      Children's Hospital in Columbus, Ohio, in children living in that city. During
      any consecutive 3-month period in 1972-1974, the greatest number of cases of
      acute leukemia diagnosed at this hospital in Columbus children was 4 (Figure 1).

PMID- 9237478
TI  - Burkitt's lymphoma--Winchester, Virginia.
AB  - Three cases of Burkitt's lymphoma (BL) have occurred since 1971 in young boys
      living in one residential section of Winchester, Virginia. Onset of illness in
      the first 2 cases (ages 9 and 15) occurred simultaneously in August 1971 (1); the
      third patient (age 8) first became ill in July 1975.

PMID- 9237479
TI  - Modulation of mesolimbic dopaminergic activity over the rat estrous cycle.
AB  - Clinical observations have suggested that ovarian steroid hormones modulate the
      symptomology of psychiatric disorders and this modulation is thought to be due to
      a protective effect of estrogen on dopaminergic activity. To test this
      hypothesis, mesolimbic dopamine (DA) activity was examined in relationship to
      endogenous hormone levels. Using in vivo electrochemical techniques, K+
      stimulated DA release was measured in the nucleus accumbens of control, intact
      cycling female rats and experimental rats which had received bilateral 6
      hydroxydopamine (6-OHDA) lesions to the medial prefrontal cortex (PFC) to produce
      subcortical hyperactivity. DA release and reuptake fluctuated with changes in
      circulating steroid levels in both control and lesion groups. In non-lesioned
      control rats, stimulated DA release peaked during diestrus I (DI) and was
      attenuated during diestrus II (DII) and estrus. DA transport, as measured by a
      change in T1/2 time, was significantly potentiated during proestrus. The
      expression of subcortical hyperactivity following lesions to the medial PFC
      appeared to be dependent on the steroid environment; during DII an increased
      responsiveness was observed while a significant decrease in K+-stimulated release
      was observed during DI. These cyclic changes in DA release were not associated
      with dramatic changes in DA transport except during proestrus when transport was
      significantly prolonged. These data suggest that cyclic fluctuation of ovarian
      steroids may modulate DA activity presynaptically through an alteration in both
      release and reuptake and that this modulation effectively dampens the expression
      of subcortical hyperactivity except under specific hormonal conditions.

PMID- 9237480
TI  - Brain-derived neurotrophic factor induced stimulation of septal choline
      acetyltransferase activity in ethylcholine mustard aziridinium treated rats.
AB  - We evaluated whether brain-derived neurotrophic factor (BDNF) can stimulate
      choline acetyltransferase (ChAT) activity in the septo-hippocampal pathway of
      ethylcholine mustard aziridinium (AF64A) and non-AF64A-treated rats. Rats
      received either AF64A (1.5 nmol/ ventricle) or a sham (non-AF64A-treated)
      injection into the lateral ventricles. BDNF infusion (at a dose range of 0.1-171
      microg) into either the lateral ventricle or hippocampus of AF64A-treated rats
      for 14 days increased septal ChAT activity (26% and 41%, respectively). BDNF did
      not reverse the decrease in hippocampal ChAT activity (20-60%) produced by AF64A.
      BDNF infusion did not change ChAT activity in the septo-hippocampal pathway of
      non-AF64A-treated rats. Thus, septo-hippocampal cholinergic neurons in AF64A
      treated rats are sensitive to BDNF while those of non-AF64A-treated rats (normal)
      are not responsive to this neurotrophin.

PMID- 9237481
TI  - Modular structures in the mushroom body of the cockroach.
AB  - The mushroom body (MB) is a higher center of the insect brain and is critical to
      olfactory and other forms of associative memory. Here, we report that repetitive
      modular subunits, which we refer to as slabs, are present in the internal matrix
      of the alpha lobe, a major output neuropil of the MB in the cockroach. The
      methods employed were osmium-ethyl gallate, Bodian-reduced silver, and Golgi
      staining procedures. A total of 15 dark and 15 pale slabs, each consisting of
      specific subsets of intrinsic neurons (Kenyon cells), alternate throughout the
      length of the alpha lobe. One of the major classes of MB output neurons, which
      are postsynaptic to Kenyon cells, exhibited segmented dendritic arbors that
      interact with every other slabs, i.e. only either dark or pale slabs. As each
      output neuron interacts with each specific set of dark or pale slabs, the slab
      likely functions as a unit for transmitting MB output signals.

PMID- 9237482
TI  - Mutation analysis of chromosome 19 calmodulin (CALM3) gene in Alzheimer's disease
      patients.
AB  - The calcium buffering capacity of lymphoblasts from patients suffering of late
      onset Alzheimer's disease (AD) has been reported to be diminished. Calmodulin is
      a calcium binding protein codified by three genes, one of them (CALM3) maps to
      chromosome 19, nearby a gene, apoE, associated with late onset AD. In this study
      we screened for structural changes in the CALM3 gene from AD patients by PCR-SSCP
      analysis. We observed several point mutations in the intronic flanking regions of
      exons 3 and 4 of CALM 3 gene. However, we failed to detect any structural changes
      in the regions encoding the calcium binding domains of this gene. Similar results
      were obtained by RT-PCR analysis of CALM3 transcripts from AD patients carrying
      apoE epsilon4 allele. It is concluded that structural alterations in the CALM3
      gene are not associated with the altered Ca2+ homeostasis shown by lymphoblasts
      from these patients.

PMID- 9237483
TI  - In vivo inhibition of veratridine-evoked release of striatal excitatory amino
      acids by the group II metabotropic glutamate receptor agonist LY354740 in rats.
AB  - In vivo microdialysis in freely moving rats was used to investigate the
      presynaptic mechanisms by which LY354740, a novel, potent, selective, and
      systemically active agonist for group II metabotropic glutamate receptors
      (mGluRs), alters glutamate neuronal transmission. Basal levels of glutamate and
      aspartate in striatal dialysates of LY354740 (10 mg/kg i.p.)-treated animals were
      not significantly different from the saline-treated control animals. In the
      saline treated controls, veratridine (100 microM) induced a 6-fold increase in
      glutamate and 9-fold increase in aspartate. However, following LY354740
      administration the veratridine-evoked release of glutamate and aspartate was
      completely prevented. These data demonstrate that LY354740 blocks the evoked
      release of endogenous excitatory amino acids, and indicate a role for group II
      mGluRs in presynaptic modulation of glutamate neuronal transmission in vivo.
      Ireland Ltd.

PMID- 9237484
TI  - NO synthase-II is transiently expressed in embryonic mouse olfactory receptor
      neurons.
AB  - Among three NO synthase (NOS) isoforms only the inducible NOS-II was localized in
      developing olfactory receptor neurons of the mouse. First NOS-II immunoreactive
      receptor cells including their processes were detected by embryonic day 11 when
      the olfactory pit starts to invaginate. Cellular staining lasted until embryonic
      day 16, and was reduced during the next few days. At embryonic day 20 no
      reactivity was found in the olfactory epithelium, whereas centripetal nerve
      fibers remained positive. This transient expression of NOS-II implies a role for
      the differentiation of early olfactory receptor neurons and synaptic plasticity.

PMID- 9237486
TI  - Temporal relationship between dynamic heart rate variability and
      electroencephalographic activity during sleep in man.
AB  - In previous sleep studies, it has been demonstrated that Poincare plots of RR
      intervals, which provide a beat to beat dynamic measure of heart rate
      variability, have distinctive and characteristic patterns according to sleep
      stages. This study was designed to evaluate the temporal relationship between
      heart rate variability and sleep electroencephalographic activity (EEG) by using
      the Pearson's interbeat autocorrelation coefficients of RR intervals derived from
      the Poincare plots. The coefficients were calculated in 12 subjects over each
      minute and were related to the profiles of EEG mean frequency (0.5-35 Hz)
      computed using a Fast Fourier Transformation algorithm. Overnight profiles of
      interbeat autocorrelation coefficients and of EEG mean frequency were found to be
      related with highly significant cross-correlation coefficients ranging between
      0.216 and 0.638 (P < 0.001). The variations in heart rate variability preceded
      changes in brain activity by 1-2 min. These results demonstrate that beat to beat
      heart rate variability and EEG activity are closely linked during sleep in normal
      man.

PMID- 9237485
TI  - Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve
      injured monkeys.
AB  - Spinal cord N-methyl-D-aspartate (NMDA) receptors play an important role in the
      transmission of acute and chronic pain. The present study investigated the
      ability of dextrorphan (DEX), a metabolite of dextromethorphan and a clinically
      safe NMDA antagonist, to attenuate the responses of nociceptive spinothalamic
      tract (STT) neurons in anesthetized monkeys. The STT cells were recorded
      extracellularly in the lumbosacral enlargement and were identified by antidromic
      activation from the ventral posterior lateral thalamic nucleus. DEX administered
      through a microdialysis fiber inserted into the dorsal horn inhibited the
      responses of STT cells in normal animals to noxious pinch and heat stimuli. In
      monkeys made neuropathic by tight ligation of the L7 or S1 spinal nerve, DEX
      significantly attenuated the responses of STT cells to noxious pinch and heat, as
      well as to innocuous brushing, pressure and von Frey filament stimuli. These
      findings strongly suggest that DEX should be considered a potentially useful
      therapeutic agent for the treatment of neuropathic pain in humans.

PMID- 9237487
TI  - Analysis of apolipoprotein E, alpha1-antichymotrypsin and presenilin-1 genes
      polymorphisms in dementia caused by normal pressure hydrocephalus in man.
AB  - Normal pressure hydrocephalus (NPH) is characterized by dementia, gait disorders
      and urinary incontinence. Apolipoprotein E (ApoE) epsilon4 allele has been
      associated with severity of dementia in Alzheimer's disease (AD) and in other
      forms of dementia. Moreover, homozygosity of the A allele of the alpha1
      antichymotrypsin (ACT) gene and of allele 1 of the presenilin-1 (PS-1) gene was
      associated with an increased risk for late onset AD. We analyzed the distribution
      of ApoE, ACT and PS-1 genotypes and the corresponding allele frequencies in 13
      NPH patients. No differences were found in ACT and PS-1 polymorphism
      distributions in the patients studied with respect to the control group. An
      increased ApoE epsilon4 allele frequency was observed in NPH patients with
      respect to controls, thus suggesting that epsilon4 allele may also be involved in
      the pathogenesis of the disease.

PMID- 9237488
TI  - Effect of sphingosine on rat glial cells: inhibition of prostaglandin E2 and
      insensitivity of nitric oxide generation.
AB  - The effect of sphingosine on lipopolysaccharide (LPS)-mediated protein kinase C
      (PKC) activation and prostaglandin E2 (PGE2) and nitric oxide (NO) production was
      studied in primary cultures of rat glial cells. Incubation of cells with LPS
      elicited translocation of PKC from the cytosolic to the membranous compartment,
      as shown by measuring PKC activity and by immunoblotting. Under these conditions,
      a sustained increase in both PGE2 and NO production was measured. Thus, PGE2
      levels were 259 +/- 28 (n = 8) and 230 +/- 48 (n = 4) (control levels 11.4 +/-
      5.2 (n = 5) and 13 +/- 7.5 (n = 3)) pg/ml, at 24 and 48 h, respectively. NO
      levels were 9.3 +/- 0.9 (n = 10) and 11.6 +/- 0.8 (n = 9) (control levels 0.4 +/-
      0.18 and 1.0 +/- 0.44) nmol/ml, at 24 and 48 h, respectively. Sphingosine, a
      naturally occurring compound, which inhibits PKC activity, elicited a
      concentration-dependent decrease in LPS-mediated PGE2 production. This inhibition
      was more pronounced after 48 h than after 24 h of incubation (IC50 = 8 and 20
      microg sphingosine, respectively). By contrast, sphingosine did not inhibit NO
      production under the same conditions. We conclude that sphingosine may be
      involved in modulation of the local inflammatory response in glial cells, at
      least in part. We also surmise that LPS-mediated PGE2 production and NO
      production are probably regulated by different mechanisms, i.e., a PKC-dependent
      and a PKC-independent mechanism.

PMID- 9237489
TI  - N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists protect
      from apoptosis induced in the lateral geniculate nucleus of rabbits exposed to
      the dark.
AB  - Mono or binocular deprivation, during early postnatal development, produces
      dramatic effects on the anatomy and physiology of the visual system. Here we
      report that dark exposure induces apoptotic cell death in the lateral geniculate
      nucleus (LGN) of adult rabbit and this may be related to activation of N-methyl-D
      aspartate (NMDA) and non-NMDA subtypes of glutamate receptors. In situ DNA
      fragmentation (TUNEL) was observed in the LGN of rabbits exposed to dark for 48
      h. Morphological changes were confirmed on hematoxylin-eosin stained brain tissue
      coronal sections. Systemic treatment with CGP 040116 or MK 801, two NMDA receptor
      antagonists, and with GYKI 52466, a non-NMDA receptor antagonist, prevented in
      situ DNA fragmentation and nuclear chromatin marginalization and condensation. In
      no instance was apoptosis seen in rabbits kept under a normal light-dark cycle.
      Our findings indicate that glutamate, acting on NMDA and non-NMDA receptors, may
      be involved in the mechanisms of apoptotic cell death induced in the LGN of adult
      rabbits exposed to darkness.

PMID- 9237490
TI  - Projection from trigeminal nuclei to neurons of the mesencephalic trigeminal
      nucleus in rat.
AB  - The mesencephalic trigeminal nucleus contains cell bodies of primary somatic
      sensory neurons that innervate the head region. The neurons resemble dorsal root
      ganglion cells but a striking difference is the presence of synaptic boutons in
      the nucleus. The present report demonstrates with anterograde tracers, the
      existence of a direct trigeminal projection from secondary sensory neurons of the
      principal and spinal nuclei to the mesencephalic nucleus. Our observations
      strongly suggest that synaptic contact may be established on the cell bodies as
      well as on the neurites of the mesencephalic neurons. These pathways could play a
      modulatory role in the processing of sensory afferent information and in the
      control of orofacial and/or oculomotor functions.

PMID- 9237491
TI  - Melatonin protects bovine cerebral endothelial cells from hyperoxia-induced DNA
      damage and death.
AB  - Hyperoxia leads to excessive formation of reactive oxygen species (ROS). ROS
      cause damage to many cellular components, including DNA. Exposure of bovine
      cerebral endothelial cells to 95 or 100% oxygen resulted in an increase in DNA
      fragmentation, the appearance of DNA ladders, and cell death with morphological
      features suggestive of apoptosis. Melatonin, an antioxidant, reduced hyperoxia
      induced DNA fragmentation and cell death in a dose-dependent manner. Results from
      the present study support the contention that ROS play a major role in DNA damage
      and apoptotic death. Melatonin is an effective agent in reducing ROS-mediated DNA
      fragmentation and death in bovine cerebral endothelial cells.

PMID- 9237493
TI  - Decreased glutamate transporter (GLT-1) expression in frontal cortex of rats with
      acute liver failure.
AB  - It has been suggested that reduced astrocytic uptake of neuronally released
      glutamate contributes to the pathogenesis of hepatic encephalopathy in acute
      liver failure. In order to further address this issue, the recently cloned and
      sequenced astrocytic glutamate transporter GLT-1 was studied in brain
      preparations from rats with ischemic liver failure induced by portacaval
      anastomosis followed 24 h later by hepatic artery ligation and from appropriate
      sham-operated controls. GLT-1 expression was studied using reverse transcriptase
      polymerase chain reaction (RT-PCR). Expression of GLT-1 transcript was
      significantly decreased in frontal cortex at coma stages of acute liver failure.
      Western blotting using a polyclonal antibody to GLT-1 revealed a concomitant
      decrease in expression of transporter protein in the brains of rats with acute
      liver failure. Reduced capacity of astrocytes to reuptake neuronally released
      glutamate, resulting from a GLT-1 transporter deficit and the consequently
      compromised neuron-astrocytic trafficking of glutamate could contribute to the
      pathogenesis of hepatic encephalopathy and brain edema, two major complications
      of acute liver failure.

PMID- 9237492
TI  - Partial inhibition of the in vitro infection of adult mouse dorsal root ganglion
      neurons by rabies virus using nicotinic antagonists.
AB  - The infection of target cells by rabies virus is effected through membrane
      receptors. Several authors have suggested that nicotinic receptors could be used
      by this virus, but no direct experimental evidence is available. In this study
      mouse dorsal root ganglia cells were treated with various nicotinic antagonists
      (dihydro-beta-eritroidine, mecamilamine, d-tubocurarin, hexametonium, alpha
      bungarotoxin and erabutoxin). After incubation, the cultures were infected with
      rabies virus. Cells were fixed, and processed for immunodetection of rabies
      virus. Treatment with mecamilamine or d-tubocurarine reduced the percentage of
      infected neurons. None of the antagonists tested changed the percentage of
      infected non-neuronal cells.

PMID- 9237494
TI  - Serotonin and human information processing: fluvoxamine can improve reaction time
      performance.
AB  - Fluvoxamine is a specific serotonin reuptake inhibitor. Recent evidence suggests
      that this antidepressive drug shortens the reaction time (RT) of healthy
      volunteers. The first objective of the present study was to decipher whether this
      effect is due to an improvement in information processing per se or to the
      adoption of an error-prone strategy. The second objective was to locate the
      effect of fluvoxamine within the series of information processing stages by means
      of Sternberg's additive factor method. After administration of a single oral dose
      of fluvoxamine (100 mg) or a placebo (randomized double-blind, cross-over
      design), eight healthy volunteers performed a choice RT task in which stimulus
      intensity, stimulus-response compatibility and response repertoire were
      manipulated. Fluvoxamine shortened RT without decreasing the accuracy of the
      responses. This demonstrates that fluvoxamine improves information processing per
      se. The effect of fluvoxamine was additive on RT with the respective effects of
      stimulus intensity and stimulus-response compatibility. This result suggests that
      fluvoxamine spares the processing stages of stimulus preprocessing and response
      selection.

PMID- 9237495
TI  - Expression of calcitonin gene-related peptide1 receptor mRNA in human trigeminal
      ganglia and cerebral arteries.
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR) using primers for the
      recently cloned human CGRP1 receptor detected mRNA expression of CGRP1 receptors
      in trigeminal ganglia and cerebral vessels, obtained at autopsy or during
      neurosurgical tumor resections. An RT-PCR product of the expected size (339 bp)
      was seen in cerebral arteries, both in the presence and in the absence of
      endothelium and in trigeminal ganglia. Sequence analysis of the RT-PCR product of
      the published sequence showed 100% homology with the human CGRP1 receptor. The
      presence of the CGRP1 receptor mRNA in human trigeminal ganglia and cerebral
      blood vessels, indicates the occurrence of both prejunctional (trigeminal) and
      postjunctional location (blood vessels) of the CGRP1 receptor.

PMID- 9237496
TI  - S100beta promotes the extension of microtubule associated protein2 (MAP2)
      immunoreactive neurites retracted after colchicine treatment in rat spinal cord
      culture.
AB  - S100beta, a glial derived calcium-binding protein with neurotrophic activity in
      the central nervous system, stimulates neurite extension of fetal raphe, cortex,
      spinal cord, and dorsal root ganglion neurons. The effects of S100beta on neurite
      length and microtubule associated protein2 (MAP2) immunoreactivity (IR) after
      microtubule disruption with colchicine were investigated in primary rat spinal
      cord culture. The incubation with S100beta (20 ng/ml) for 3 h after exposure to
      colchicine (10(-6) M) for 30 min altered the distribution of MAP2-IR. The length
      of MAP2-IR neurites increased by 65% compared to that in colchicine treatment
      alone. MAP2-IR intensity in the cell body was reduced by 26% compared to that in
      colchicine treatment alone. These results indicate that neurites shrink when the
      microtubular cytoskeletal system is disrupted and S100beta rapidly promotes re
      assembly and/or stabilization.

PMID- 9237497
TI  - Malignant hyperthermia susceptibility, an autosomal dominant disorder?
AB  - A large series of Swedish nuclear families, in which malignant hyperthermia (MH)
      reactions had occurred during anaesthesia, have been examined with respect to
      malignant hyperthermia susceptibility. In vitro contracture tests (IVCT) of
      muscle strips were conducted to diagnose MH status. Included in this series were
      some families where only one of the parents was tested by IVCT, while in 79 of
      the families both parents were tested by IVCT. Six known mutations in the gene
      encoding the calcium release channel of sarcoplasmic reticulum in skeletal muscle
      (the RYR1 gene), believed to cause MHS in man, were searched for in 41 nuclear
      families. The present paper focuses on findings in eight families, where both
      parents were malignant hyperthemia negative (MHN), while at least one child was
      either malignant hyperthermia susceptible (MHS) or malignant hyperthermia
      equivocal (MHE). There was no suggestion of non-paternity. The RYR1 mutations
      investigated were Arg163Cys, Gly341Arg, Ile403Met, Arg614Cys, Gly2433Arg and
      Arg2434His. No family had any of the six RYR1 mutations searched for.

PMID- 9237498
TI  - Association of the renin gene polymorphism with essential hypertension in a
      Chinese population.
AB  - To study the association of renin gene polymorphism with essential hypertension
      in the Chinese population, 86 hypertensive and 107 normotensive subjects were
      enrolled from an epidemiologic survey. Leukocyte DNA was extracted and digested
      with Hind III and Bgl I restriction enzymes. Southern hybridization was done with
      digoxigenin-incorporated renin gene probes generated by polymerase chain
      reaction. The restriction fragments were detected by anti-digoxigenin antibody
      and enzyme methods. Two Hind III polymorphysms of the renin gene (8.7 kb and 6.2
      kb) were identified. The allele frequences were 129(75%) and 43(25%),
      respectively, in hypertensives; they were 139(65%) and 75(35%), respectively, in
      normotensives (chi2 = 4.074, p = 0.044). The genotypes of 8.7/8.7,8.7/6.2 and
      6.2/6.2 were significantly different between hypertensives and normotensives,
      being 45(52%), 39(45%), 2(3%) and 48(45%), 43(40%), and 16(15%), respectively
      (chi2 = 9.002, p = 0.11). The Bgl I polymorphism did not show a difference
      between hypertensives and normotensives. Thus, we conclude that the renin gene
      Hind III polymorphysm is associated with hypertension in this Chinese population.

PMID- 9237499
TI  - Extending the overlap of three congenital overgrowth syndromes.
AB  - We present the case of a male infant, born prematurely (at 33 weeks gestation)
      with macrosomia, disproportionate macrocephaly, facial dysmorphism, short penis
      and a small umbilical defect. He had a large ASD and was ventilated from birth
      for respiratory distress syndrome. He died at 12 hours of age despite neonatal
      ITU care. Post-mortem examination showed highly lobulated kidneys with nodules of
      blastema and foci of hamartomatous change in the medulla. Prominence of
      pancreatic islet cells and expansion of hepatic portal tracts were also noted.
      His mother has minor cervical spine abnormalities. We discuss the differential
      diagnosis and the difficulty in confidently assigning a diagnosis to this
      patient, as considerable overlap is becoming evident between Simpson-Golabi
      Behmel syndrome and Perlman syndrome.

PMID- 9237500
TI  - Photoanthropometric study of craniofacial traits in individuals with Williams
      syndrome.
AB  - A photoanthropometric method, which enables an objective description of facial
      structures, was used to better delineate the craniofacial characteristics of 29
      individuals with Williams syndrome (WS; 18 males and 11 females) between the ages
      of 0 to 10 years, with an average age of 4.0 years. Facial parameters were
      measured from strict frontal and profile photographic 35-mm slides and compared
      with other facial measurements from the same face (e.g., palpebral fissure width
      to bizygomatic diameter). Sixteen photoanthropometric craniofacial indices were
      developed from 20 measurements (3 from the frontal face, 2 from the eye region, 3
      from the nose region, 2 from the mouth region, 4 from the profile face, and 6
      from the ear region). Based on our measurements of 29 Williams syndrome
      individuals, two parameters (e.g. nose length to midface height and palpebral
      fissure width to bizygomatic diameter) were outside the normal range when
      compared with photoanthropometric index standards for age established by Stengel
      Rutkowski et al. from white control children. Overall, our data supported a high
      midface height, broad palpebral fissure width, broad interalar distance, short
      length of back of nose, prominent ears with long narrow conchae, increased chin
      height, increased inclination of the ears and a narrow bizygomatic diameter in WS
      patients. These craniofacial parameters (many not previously evaluated in WS
      patients) may become useful for early detection, and aid in the diagnosis and
      study of the development of the characteristic face in Williams syndrome
      subjects.

PMID- 9237501
TI  - On the many faces of Leber hereditary optic neuropathy.
AB  - Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder,
      associated with mutations in the mitochondrial DNA, which is notorious for its
      aspecific presentations. Two pedigrees are described with cases that are atypical
      for LHON with respect to sex, age of onset, interval between the eyes becoming
      affected, course of the disease, concomitant disorders, additional test results,
      final visual acuity, and/or results of mtDNA analysis. Moreover, the pedigrees
      themselves did not suggest maternal inheritance. We analysed the diagnostic and
      clinical genetic difficulties related to the atypical aspects of these pedigrees.
      We conclude that mtDNA analysis is justified in every case of optic nerve atrophy
      with no clear cause. Identification of one of the three LHON specifically
      associated mtDNA mutations is essential to confirm the diagnosis.

PMID- 9237502
TI  - CpG hotspot mutations at the LDL receptor locus are a frequent cause of familial
      hypercholesterolaemia among South African Indians.
AB  - Mutation analysis of genomic DNA samples obtained from seven unrelated South
      African Indians with familial hypercholesterolaemia (FH) revealed two novel and
      two recurrent missense mutations in the low density lipoprotein receptor (LDLR)
      gene. The novel mutations are transversions of C to G and A to T at nucleotide
      positions 1215 (N384K) and 2356 (S765C), respectively. The known mutations were
      detected in CpG dinucleotides at bases 661 and 682, respectively, in the mutation
      rich exon 4 of the LDLR gene. Mutation D200Y was found in a single FH family,
      while mutation E207K was detected in two apparently unrelated Indian families on
      a new mutual haplotype. Analysis of published mutations including our new data
      has shown that more than 50% of the different LDLR gene mutations identified to
      date in South African Indians occur at CpG hotspots.

PMID- 9237503
TI  - Codon 89 polymorphism of the human 5alpha-steroid reductase type 2 gene.
AB  - The existence of a genetic polymorphism within the coding region of the human
      5alpha-steroid reductase type 2 (5alpha-SR2) gene is reported in a Mexican
      population. Genotypic variation was assessed in 100 unrelated, healthy volunteers
      (50 males; 50 females), using single-stranded conformational polymorphism and
      direct sequencing analysis. Examination of exon 1 DNAs disclosed the presence of
      sequences encoding for valine (GTA) or leucine (CTA) at codon 89 of the gene. Of
      the subjects screened, 45% were homozygous for GTA (89Val), 50% had a
      heterozygous pattern GTA/CTA (89Val/89Leu) and the remaining 5% were homozygous
      for CTA (89Leu). These data support the view that the G/C condition at codon 89
      of the 5alpha-SR2 gene represents a silent polymorphism which does not alter
      phenotypical development in the human.

PMID- 9237504
TI  - Three cases of trisomy 13 mosaicism and a review of the literature.
AB  - We describe three cases of trisomy 13 mosaicism and review the literature. The
      phenotype ranges from a severe form similar to Patau syndrome, through to
      physical and mental normality. This range presumably reflects the proportion and
      tissue distribution of the trisomic cell line. The percentage of trisomic cells
      in lymphocytes correlates poorly with the observed phenotype.

PMID- 9237505
TI  - Polycystic kidney disease, biliary dysgenesis in a patient with Larsen's
      syndrome.
AB  - Larsen's syndrome is characterised by multiple joint dislocations, flat face and
      talipes equinovarus. There is an autosomal dominant form and also a more severe
      autosomal recessive form. Several types of polycystic kidney disease have been
      reported in children. In this report we present an infant with a severe form of
      Larsen's syndrome (thought to be lethal Larsen-like), infantile-type polycystic
      kidney disease, biliary dysgenesis and osteosclerosis.

PMID- 9237506
TI  - A case of Carpenter syndrome diagnosed in a 20-week-old fetus with postmortem
      examination.
AB  - Carpenter syndrome (acrocephalopolysyndactyly type II) is an autosomal recessive
      syndrome. The case we present was diagnosed prenatally at 20 weeks. Postmortem
      examination revealed severe central nervous system malformations. The central
      nervous system anomalies in this 23-week-old fetus merit emphasis, since these
      anomalies in such a young fetus may explain Carpenter syndrome cases, which do
      not improve in spite of early surgical intervention.

PMID- 9237507
TI  - A case of mosaic trisomy 2 diagnosed at amniocentesis in an abnormal fetus and
      confirmed in multiple fetal tissues.
AB  - Pseudomosaicism for trisomy 2 is a relatively common finding at amniocentesis.
      However, genuine trisomy 2 mosaicism is extremely rare. As a result, very few
      cases have been described and little information is available with which to
      counsel the parents of an affected fetus. We describe a case of mosaic trisomy 2
      diagnosed at amniocentesis in a fetus with multiple anomalies on ultrasound scan.
      Following termination of pregnancy, the fetus was found to have mild dysmorphic
      features, together with an absent gall bladder, cystic left kidney, a 13th left
      rib and mild unilateral talipes. The presence of trisomy 2 cells was confirmed by
      both standard cytogenetic analysis and fluorescent in-situ hybridisation
      techniques in multiple fetal tissues, as well as in the cord and placenta.

PMID- 9237508
TI  - Recurrent brachial plexus neuropathy in a family with subtle dysmorphic features 
      - a case of hereditary neuralgic amyotrophy.
AB  - Brachial plexus neuropathy is a disorder which usually occurs sporadically, and
      is characterized by pain and varying degrees of weakness in one or both upper
      limbs. Some patients experience recurrent episodes. The hereditary form is
      usually associated with dysmorphic features. We describe a mother and son with
      recurrent episodes. Despite very slight dysmorphic features, we believe this is a
      case of the inherited form.

PMID- 9237509
TI  - Identification of the parental origin of polysomy in two 49,XXXXY cases.
AB  - The parental origin and mechanism of formation of polysomy X were studied in two
      polysomic cases, using four X-linked restriction fragment length polymorphisms,
      three (CA)n dinucleotide repeat sequences and one variable number tandem repeat
      (VNTR) locus as genetic markers. A nonradioactive technique based on the
      hybridization of the polymerase chain reaction (PCR) product was developed for
      the analysis of dinucleotide repeats. Segregation analysis using different
      nonradioactive approaches based on the PCR, revealed that all four X chromosomes
      were of maternal origin. These data provide additional evidence of an identical
      mechanism of successive nondisjunctions in maternal meiosis I and II.

PMID- 9237510
TI  - A novel mutation M-21V in exon 1 of the low density lipoprotein receptor gene
      causing familial hypercholesterolemia.

PMID- 9237511
TI  - Lateral septal vasopressin in rats: role in social and object recognition?
AB  - The capacity of male rats to remember familiar conspecifics is called social
      recognition. It is a form of short-term memory modulated by lateral septal (LS)
      vasopressin (VP). The specificity of this phenomenon was studied by examining
      whether recognition of previously investigated objects is also under control of
      lateral septal VP. For social recognition male Wistar rats were confronted with
      juveniles for 5 min. Re-exposure to the same juvenile took place after 30 or 120
      min, or with a different juvenile after 30 min. This procedure was duplicated for
      object recognition using a plastic food cup or a 50 ml Erlenmeyer flask. After
      these initial tests osmotic minipumps and brain cannulae were implanted, infusing
      VP receptor antagonist into the LS (dPTyr(Et)AVP, 1 ng/0.5 microl/h, bilateral).
      Animals were re-tested for social and object recognition using 30 min re-test
      interval (same juvenile or object). We reproduced previous reports concerning
      social recognition; animals recognized juveniles after 30 min, not after 120 min
      and VP antagonist treatment blocked recognition. Testing for object recognition
      revealed a reduction in investigation time at the 30 min interval (same and
      different object), but not after 120 min. VP antagonist treatment was unable to
      block object recognition. The data suggest that, in contrast to social
      recognition, object recognition reflects a form of habituation, which is not
      under the control of lateral septal VP.

PMID- 9237512
TI  - Secretoneurin-like immunoreactivity in rat sympathetic, enteric and sensory
      ganglia.
AB  - Distribution of secretoneurin-like immunoreactivity (SN-LI) was studied in the
      rat sympathetic ganglia/adrenal gland, enteric and sensory ganglia by
      immunohistochemical methods. SN-LI nerve fibers formed basket-like terminals
      surrounding many of the postganglionic neurons of the superior cervical,
      stellate, paravertebral chain ganglia, coeliac/superior mesenteric and inferior
      mesenteric ganglia. Postganglionic neurons of the superior cervical and other
      sympathetic ganglia exhibited low-to-moderate levels of SN-LI. In all these
      sympathetic ganglia, clusters of small diameter (< 10 microm) cells, which may
      correspond to the small intensely fluorescent (SIF) cells, were found to be
      intensely labeled. Surgical sectioning or ligation of the cervical sympathetic
      trunk for 7-10 days resulted in a nearly total loss of SN-LI fibers in the
      superior cervical ganglia, whereas immunoreactivity in the postganglionic neurons
      and small diameter cells remained essentially unchanged. In the thoracolumbar and
      sacral segments of the spinal cord, SN-LI nerve fibers were detected in the
      superficial layers of the dorsal horn as well as in the intermediolateral cell
      column (ILp). Occasionally, SN-LI somata were noted in the ILp. SN-LI nerve
      fibers formed a delicate plexus underneath the capsule of the adrenal gland, some
      of which traversed the adrenal cortex and reached the adrenal medulla. While
      heavily invested with SN-LI nerve terminals, chromaffin cells seemed to express a
      low level of SN-LI. In the enteric plexus, varicose SN-LI nerve fibers and
      terminals formed a pericellular network around many myenteric and submucous
      ganglion cells; the ganglionic neurons were lightly to moderately labeled. A
      population of ganglion cells in the dorsal root, nodose and trigeminal ganglia
      exhibited moderate-to-strong SN-LI. The detection of SN-LI in nerve fibers and
      somata of various sympathetic ganglia, enteric plexus and adrenal medulla and in
      somata of the sensory ganglia implies an extensive involvement of this peptide in
      sympathetic, enteric and sensory signal processing.

PMID- 9237513
TI  - Chronic postnatal hypoxia increases the numbers of cortical neurons.
AB  - Premature infants have been shown to undergo prolonged periods of sublethal
      hypoxia. There is considerable evidence to link these hypoxic events with
      neurodevelopmental disorders. As an animal model for this clinical problem, rats
      were raised from the third day of life in a chamber where the O2 level was 9.5%.
      After 30 days of hypoxia the rats were sacrificed and their brains processed for
      determination of the number of cortical neurons. This work was performed to test
      the hypothesis that chronic hypoxia would result in increased cortical cell
      death. The hypoxic rats had lower body and brain weights as well as decreased
      cortical volumes. However, hypoxic rats had increased neuronal density and
      significantly more cortical neurons than controls (P < 0.05). The results of this
      study suggest that chronic sublethal hypoxia may lead to reduction in the amount
      of programmed cell death in the developing neocortex.

PMID- 9237515
TI  - Regulation of glycogen content in rat pineal gland by norepinephrine.
AB  - In the rat pineal gland the glycogen stores were cytochemically localized in
      astrocytes and pinealocytes. Moreover, it was found that norepinephrine (NE)
      induced a time- and concentration-dependent reduction in pineal glycogen content
      and yielded lactic acid. The NE effect was prevented by blocking alpha1- but not
      alpha2 or beta-adrenoceptors. Activation of alpha2-adrenoceptors induced a small
      decrease in glycogen levels that could have pre- and postsynaptic components.
      Activation of beta-adrenoceptors with 10(-12)-10(-3) M isoproterenol (ISO)
      induced a bell shape concentration-response curve, presumably due to
      desensitization, since the response induced by 10(-4) M ISO was greater with
      shorter period of stimulation. On the other hand, activation of alpha1
      adrenoceptors with 10(-12)-10(-3) M phenylephrine (PHN) induced a hyperbolic
      concentration-response curve with a maximum at concentrations above 10(-8) M.
      Moreover, treatment with ISO drastically reduced the response induced by PHN
      concentrations lower but not higher than 10(-6) M, favoring a concentration
      dependent response between 10(-6) and 10(-4) M PHN, similar to that induced by
      equimolar NE concentrations. Thus, the NE-induced reduction in glycogen content
      of the rat pineal gland is mainly mediated by alpha1-adrenoceptors and modulated
      by intracellular mechanisms activated by beta-adrenoceptors.

PMID- 9237514
TI  - Catecholaminergic regulation of proliferation and survival in rat forebrain
      paraventricular germinal cells.
AB  - We have investigated the possible role of alpha1-adrenoreceptors in regulating
      the germination of progenitor cells cultured from embryonic rat neocortex. High
      binding levels of the alpha1-selective radioligand 3[H]prazosin were detected in
      the forebrain of the rat embryo at E13, and the greatest density of binding sites
      was localized to the ventricular and subventricular zones. Catecholamine
      containing axon terminals were present in these zones in the same period.
      Germinal neuroepithelial cells retained specific 3[H]prazosin binding in culture.
      Approximately 25% of cells in culture displayed complex intracellular Ca2+
      transients in response to phenylephrine, many of which were abolished with the
      alpha1B antagonist, chloroethylclonidine. Cultures exhibited concentration
      dependent catecholamine stimulation of DNA synthesis mediated by alpha1 receptors
      in serum-limited conditions. Neuroepithelial cells were labelled via their
      ventricular processes by intraventricular injection of Fast blue in E13 embryos
      prior to transfer of the neocortex to dissociated cell culture. Many of labelled
      cells were present in culture in germinal foci. Some cells which migrated from
      these foci underwent apoptosis, as determined by TUNEL in situ hybridization.
      During a transitory period of up to 48 h in culture, alpha1-adrenoreceptor
      activation by phenylephrine or noradrenaline increased the number of surviving
      cells. Apoptosis was observed in vivo in both ventricular and subventricular
      zones of the neocortex from E13 to E15 in increasing numbers. We propose that
      both the supply of noradrenaline to forebrain germinal cells, and the expression
      of alpha1-adrenoreceptors on their surface could act to determine whether they
      die or continue to proliferate.

PMID- 9237516
TI  - Prediction of delayed ischemic injury with diffusion-weighted MRI following
      temporary middle cerebral artery occlusion in rats.
AB  - Early reductions in the apparent diffusion coefficient of water (ADC) during
      focal cerebral ischemia are often reversible with reperfusion. With sustained
      ischemia, the magnitude of the ADC reduction generally increases with time, which
      could reflect increased severity of ischemic damage. Thus, a threshold in ADC
      reduction may exist beyond which damage can not be reversed with reperfusion. The
      goal of this study was to determine if such a threshold exists that is
      independent of the duration of ischemia in a rat model. Rats were subjected to
      either 30, 60, or 90 min of temporary middle cerebral artery occlusion. ADC maps
      acquired just before and 30 min after reperfusion were compared to histology
      performed after a 72 h survival period to determine the relationship between ADC
      reduction and final ischemic injury. Significant variability in tissue recovery
      was observed for the 30 min group. Regions with ADC reductions of up to 45% often
      recovered, while some regions not exhibiting any change in ADC during occlusion
      showed ischemic injury at 72 h. Similar observations were made in cortical
      regions of the 60 min group. In the caudate-putamen, reduced ADC was often
      associated with ischemic injury. For the 90 min group, results for the caudate
      putamen were similar to those for the 60 min group, while reduced ADC was a much
      better predictor of final ischemic injury in cortical regions than it was in both
      the 30 and 60 min groups. Thus, no single threshold of ADC reduction that was
      independent of the duration of ischemia was associated with irreversible injury.

PMID- 9237517
TI  - Activin exerts a neurotrophic effect on cultured hippocampal neurons.
AB  - Activin is a member of the transforming growth factor (TGF)-beta superfamily,
      which comprises a growing list of multifunctional proteins that serve as
      regulators of cell proliferation and differentiation. Recently, activin was shown
      to regulate the neurotransmitter phenotype in peripheral neurons. It is also a
      potent survival factor for neurogenic clonal cell lines, retinal neurons and
      midbrain dopaminergic neurons. We have studied the effect of activin on
      hippocampal cells which show abundant expression of activin receptors or binding
      sites. Exposure of primary cultures of rat hippocampal neurons to activin
      supported neuronal survival. This neurotrophic action of activin was blocked by
      treatment with the tyrosine kinase inhibitor genistein or the protein kinase C
      inhibitor calphostin C. However, the Ca2+/calmodulin kinase inhibitor KN-62 had
      no effect. Nicardipine, a blocker of the L-type Ca2+ channel, also inhibited the
      neurotrophic effect of activin. Furthermore, activin potentiated the
      depolarization-induced elevation in intracellular Ca2+ concentration ([Ca2+]i).
      The neurotrophic effect and the potentiation of depolarization-induced increase
      of [Ca2+]i caused by activin were completely abolished by the protein synthesis
      inhibitor cycloheximide. These results suggest that activin supports neuronal
      survival by increasing the expression of voltage-dependent Ca2+ channel through
      the action of a tyrosine kinase and of protein kinase C, but not of
      Ca2+/calmodulin kinase.

PMID- 9237518
TI  - Saturation kinetics, specificity and NBMPR sensitivity of thymidine entry into
      the central nervous system.
AB  - It was not until the development of a technique that could measure the brain
      uptake of slowly moving substrates, that the saturable transport system at the
      blood-brain barrier (BBB) for the pyrimidine deoxyribonucleoside, thymidine, was
      demonstrated. The aim of this present study was to further characterize this
      saturable uptake system at the blood-brain and blood-CSF barriers in terms of
      specificity, 6-(4-nitrobenzyl)thio-9-beta-D-ribofuranosylpurine (NBMPR)
      sensitivity and saturation kinetics by means of the in situ brain perfusion
      technique in anaesthetized guinea pigs. The results indicated that the transport
      system identified for [3H]thymidine can also transport other pyrimidine
      deoxyribonucleosides (deoxycytidine) and pyrimidine ribonucleosides (uridine) and
      is partially NBMPR-sensitive. In addition, guanosine, monocarboxylic acids,
      hexoses or amino acids were not substrates for the transport system. Further
      studies revealed that the transport system for [3H]thymidine at the BBB has a low
      affinity (Km 0.20 +/- 0.06 mM), but a relatively high capacity (Vmax 1.06 +/-
      0.08 nmol min(-1) g(-1)). Overall, this study is indicative of a NBMPR-sensitive
      (es) facilitative transport system for [3H]thymidine and the likely presence of a
      NBMPR-insensitive and/or sodium-dependent transport system of the N2 (cit) type
      at the blood-brain and blood-CSF barriers of the guinea pig.

PMID- 9237519
TI  - Serotonin depletion during synaptogenesis leads to decreased synaptic density and
      learning deficits in the adult rat: a possible model of neurodevelopmental
      disorders with cognitive deficits.
AB  - Studies in the past have revealed serotonin to play a role in regulating the
      development and maturation of the mammalian brain, largely through the release of
      the astroglial protein S-100beta. S-100beta plays a role in neurite extension,
      microtubule and dendritic stabilization and regulation of the growth associated
      protein GAP-43, all of which are key elements in the production of synapses.
      Depletion of serotonin, and thus of S-100beta, during synaptogenesis should lead
      to a loss of synapses and the behaviors dependent on those synapses. The current
      study was undertaken to test this hypothesis. In order to assess the influence of
      serotonin we have looked at the synaptic density in the adult after depletion, by
      using immunodensitometry of synaptic markers (synaptophysin and MAP-2) and by
      studying behaviors thought to be highly dependent on synaptic plasticity and
      density. Male Sprague-Dawley rats were depleted of serotonin on postnatal days
      (PND) 10-20 by treating with the tryptophan hydroxylase inhibitor
      parachlorophenylalanine (PCPA; 100 mg/kg, s.c.). On PND's 30 and 62, animals were
      perfused for immunodensitometry. Littermates were used for behavioral testing. At
      PND 55-62, the animals were tested in an interchangeable maze with olfactory cues
      and in an eight-arm radial maze. Our results show a loss of both synaptic markers
      in the hippocampus on PND 30. At PND 62, the only remaining loss was of the
      dendritic marker MAP-2. The animals had deficits in both behaviors tested,
      suggestive of spacial learning deficits and of the failure to extinguish learned
      behaviors or to re-learn in a new set. Our findings show the long-term
      consequences of interfering with the role of serotonin in brain development on
      the morphology and function of the adult brain. These findings may have
      implications for human diseases, including schizophrenia, thought to be related
      to neurodevelopmental insults such as malnutrition, hypoxia, viruses or in utero
      drug exposure. Moreover, they provide further insights into the functioning of
      serotonin and S-100beta in development and aging.

PMID- 9237520
TI  - The involvement of dopamine D2 receptors, but not D3 or D4 receptors, in the
      rewarding effect of brain stimulation in the rat.
AB  - To identify the subtype of dopamine receptors critically involved in the
      rewarding effect of brain stimulation, four dopamine antagonists were
      intracranially injected in 25 rats. The importance of dopamine D1 receptors had
      been demonstrated previously by using SCH 23390, a highly selective D1
      antagonist. Rats were implanted with electrodes into the medial forebrain bundle
      and cannulae into either one of the following structures: the nucleus accumbens,
      the vicinity of the islands of Calleja, or the ventral tegmental area, all
      ipsilateral to the electrodes. The animals were trained to press a bar for
      electrical stimulation, and the frequency-response functions were plotted before
      and after injection of each dopamine antagonist through the cannulae. Raclopride
      and haloperidol, which have high affinities for D2 receptors, reduced the
      rewarding effect after injection into any one of the three cannula sites. Neither
      (+)-UH232, a selective D3 antagonist, nor clozapine, a D4 antagonist, influenced
      the rewarding effect. The results suggest that dopamine D2, but not D3 or D4,
      receptors are critically involved in producing the rewarding effect of brain
      stimulation.

PMID- 9237521
TI  - The effects of intra-accumbens neurotensin on sensorimotor gating.
AB  - Neurotensin is a neuropeptide which coexists with mesolimbic dopamine. Previous
      studies have shown that centrally administered neurotensin can modulate the
      activity of mesolimbic dopamine with a profile similar to neuroleptics. For
      example, infusions of neurotensin into the nucleus accumbens inhibit amphetamine
      induced hyperlocomotion. Prepulse inhibition (PPI) occurs when a weak prestimulus
      ('prepulse') inhibits the amplitude of the startle response to an intense
      stimulus ('pulse'). PPI is an operational measure of sensorimotor gating which is
      strongly regulated by mesolimbic dopamine. This study examined the effects of
      various doses of neurotensin infused into the nucleus accumbens of rats on the
      prepulse inhibition (PPI) of their acoustic startle reflex. Neurotensin (0.25-5.0
      microg) was infused into the nucleus accumbens of rats. Animals then received
      subcutaneous injections of amphetamine (2 mg/kg) or saline and were placed in
      startle chambers where measures of startle amplitude and PPI were obtained.
      Neurotensin increased baseline PPI and blocked amphetamine-induced disruption of
      PPI in a dose-dependent fashion. The lowest dose of neurotensin tested (0.25
      microg) significantly increased baseline PPI and both 0.25 and 1.0 microg
      neurotensin blocked amphetamine-induced decreases in PPI. The 5.0 microg dose of
      neurotensin had no significant effect on prepulse inhibition. Neurotensin had no
      effect on the amplitude of the acoustic startle reflex in amphetamine- or saline
      treated rats. The results suggest that intra-accumbens neurotensin has a
      significant, dose-dependent effect on sensorimotor gating in which lower doses
      (0.25-1.0 microg) exhibit a neuroleptic-like action.

PMID- 9237522
TI  - Opiate modulation of dynorphin conversion in primary cultures of rat cerebral
      cortex.
AB  - Rat brain cortical cells in primary culture were used to investigate long-term
      effects of opiates on endopeptidases acting on dynorphin peptides. Enzyme
      activity in the soluble fraction of the cells converted dynorphin B to Leu
      enkephalin-Arg6 and to a lesser extent to Leu-enkephalin. Five day treatment with
      10 microM morphine increased the conversion to Leu-enkephalin-Arg6 by 370%. This
      effect was prevented by the presence of naloxone in the culture medium. The
      opiate-inducible activity was directed to the Arg-Arg bond in dynorphins with
      preference for dynorphin B > alpha-neoendorphin > > dynorphin A. The Km for the
      generation of Leu-enkephalin-Arg6 from dynorphin B was 40 microM. Enzyme activity
      was inhibited by dynorphin fragments, in the following order of potency:
      dynorphin A(1-13) > A(2-13) > A(1-17) > A(2-17) and by SH-reagents, suggesting
      the presence of a cysteine-protease. The opiate-stimulated dynorphin-converting
      enzyme (DCE)-activity affects the balance between dynorphin peptides (selective
      for kappa-opioid receptors) and enkephalin peptides (selective for delta-opioid
      receptors). Since both types of opioid peptides can influence the development of
      opiate tolerance, the change in the extent of this transformation may be
      functionally important.

PMID- 9237523
TI  - Decreased experimental anxiety and voluntary ethanol consumption in rats
      following central but not basolateral amygdala lesions.
AB  - A long-debated 'tension reduction' hypothesis postulates anti-anxiety effects to
      be important for ethanol reward, and states that elevated anxiety levels might
      predispose for ethanol consumption and addiction. Human data are contradictory,
      possibly due to heterogeneity of patient samples. In rats, baseline levels of
      experimental anxiety have been reported to correlate with voluntary ethanol
      consumption. Here, we addressed the possibility that mechanisms underlying
      experimental anxiety might be causally related to regulation of voluntary ethanol
      intake. Rats were bilaterally lesioned in central amygdala using microinjections
      of ibotenic acid. This resulted in a robust release of punished drinking in a
      modified Vogel conflict test, an effect typically seen with anxiety reducing
      drugs. This effect was specific, as unpunished drinking was unaffected by the
      lesion. On the elevated plus-maze, central amygdala lesions did not affect
      behaviour under baseline conditions, but attenuated the anxiogenic effect of
      restraint stress. Measures of locomotor activity were not affected. Voluntary
      ethanol consumption was examined in a two-bottle, free choice paradigm. Ethanol
      intake was markedly decreased in the lesion group. Total fluid intake was not
      affected. Basolateral amygdala lesions, which did not affect conflict behaviour,
      also left ethanol intake unaffected. These results are consistent with previous
      reports of an important role for central amygdala in anxiety related behaviours,
      and suggest that cell bodies located in central amygdala might be important in
      this context. Further, our results support a relation between experimental
      anxiety and voluntary ethanol consumption.

PMID- 9237524
TI  - The electrical activity is impaired in the red nucleus of dt(sz) mutant hamsters
      with paroxysmal dystonia: an EEG power spectrum analysis of depth electrode
      recordings.
AB  - The genetically dystonic (dt(sz)) hamster is an animal model of paroxysmal
      dystonia that displays attacks of sustained abnormal movements and postures in
      response to mild stress. Dysfunctions within the basal ganglia may be critically
      involved in the pathophysiology of dystonia in mutant hamsters. Furthermore,
      previous observations from autoradiographic studies pointed to an altered neural
      activity in the red nucleus (RN). In the present study, computerized EEG spectral
      analysis of depth electrode recordings from the RN was performed before and after
      dystonic attacks in freely moving dt(sz) hamsters and compared to age-matched non
      dystonic controls. No epileptic activity was seen in any of the recordings,
      substantiating previous notions that paroxysmal dystonia in these mutants has no
      epileptogenic basis. The predominant EEG changes in RN of dystonic hamsters were
      a decrease in total power over the range of 1.25-42.00 Hz, a decrease in maximum
      power and a shift of frequency at maximum power to lower frequencies. With regard
      to selected frequency bands, there was a decrease in the alpha, beta and gamma
      band. Although the observed changes of neural activity in the RN are probably
      based on a primary dysfunction in related structures, the present data
      demonstrate its importance in the expression of dystonic movements.

PMID- 9237525
TI  - Parvalbumin disappears from GABAergic CA1 neurons of the gerbil hippocampus with
      seizure onset while its presence persists in the perforant path.
AB  - Mongolian gerbils are epilepsy prone animals, a trait observable at the
      behavioural level during the 2nd month of life. As a unique species difference,
      gerbils express the calcium-binding protein parvalbumin (PV) in the perforant
      path from the entorhinal cortex to the hippocampus. In this study, we determined
      the time of appearance of PV in the layer II neurons of the entorhinal cortex and
      the perforant path terminals in gerbils between post-natal days 30 and 50. Signs
      of low grade seizures were observed in few animals from P40 onward. PV stain in
      the entorhinal cortex and perforant path terminals was already detectable at P30,
      well before the onset of behavioural seizures and did not change with age. It is
      suggested that the presence of PV in this pathway may be related to the
      generation early in life of an epileptogenic focus in the limbic forebrain.
      Altered inhibitory hippocampal circuits have also been suggested as a cause of
      seizures in the gerbil. Therefore, we quantitated hippocampal GABA-immunoreactive
      neurons and the PV-immunoreactive subpopulation. A group of gerbils with a high
      density of stained pyramidal interneurons in CA1 and one lacking PV-stained
      perikarya could be distinguished at P40 and P50. The density of GABA
      immunoreactive nerve cells however, remained the same in both groups and through
      the ages studied. Thus, perikaryal PV is lost from intact GABAergic nerve cells
      at the same time as behavioural seizures are observed. The loss of PV from
      GABAergic neurons may affect their functional properties and be instrumental for
      the maintainance of behavioural seizures.

PMID- 9237526
TI  - Menadione-induced tau dephosphorylation in cultured human neuroblastoma cells.
AB  - Oxidative stress has been implicated in the mechanism of aging and
      neurodegenerative disorders such as Alzheimer's disease (AD). Menadione causes
      oxidative stress by generating reactive oxygen species through its redox cycling
      and these free radicals are detoxified subsequently at the expense of
      intracellular thiol homeostasis. In non-neuronal cells, the cytoskeleton is a
      prime target of menadione-induced thiol oxidation. We used cultured human
      neuroblastoma MSN cells in this study to determine how tau proteins in neuronal
      cells are affected by menadione exposure. Menadione caused a dose-dependent thiol
      oxidation in these cells just like their non-neuronal counterparts. A prominent
      consequence of such oxidative insult in these neuronal cells was tau
      dephosphorylation. This dephosphorylation resulted in disappearance of
      phosphorylated 57-kDa tau with a concomitant emergence of 53-kDa tau whose full
      length nature is indicated by its reactivity with antibodies Alz 50, Tau-1 and
      Tau-46. Immunochemical analyses using phosphorylation-dependent immunoprobes Tau
      1 and PHF-1 with the aid of alkaline phosphatase demonstrated that 53-kDa tau was
      derived from dephosphorylation of 57-kDa tau. Despite its effect on thiol
      oxidation, menadione treatment did not lead to cytoskeletal changes reminiscent
      of the neurofibrillary tangles of AD. The data thus indicate that tau
      dephosphorylation constitutes a major feature of the menadione-induced oxidative
      injury in these neuronal cells.

PMID- 9237527
TI  - Ischemic preconditioning: a long term survival study using behavioural and
      histological endpoints.
AB  - In this study we sought to determine if ischemic preconditioning provided long
      term behavioral and histological protection. A second goal was to see if ischemic
      preconditioning conveys its protective effect on CA1 neurons by altering post
      ischemic brain temperature. While preconditioning episodes of short duration
      ischemia (i.e. 1.5 min) provided significant histological protection of CA1
      pyramidal cells against a subsequent severe ischemic insult (i.e. 5 min), this
      did not result in complete behavioural protection. Preconditioned ischemic
      animals initially displayed habituation deficits in an open field test that were
      comparable to untreated ischemic gerbils. A significant decline in CA1
      preservation in preconditioned animals was observed when survival time was
      extended from 10 (81% protection) to 30 (53% protection) days. In addition,
      protection was not observed in the subiculum and CA2 sector of the hippocampus
      where consistent damage was observed in 21/22 gerbils. Ischemic preconditioning
      did not markedly affect post-ischemic brain temperature suggesting that the
      observed protection was not due to a reduction in temperature during or after the
      severe ischemic insult. The lack of functional protection within the first 10
      days after ischemia, along with the decline of cellular preservation over time,
      suggests that this paradigm may not provide permanent protection.

PMID- 9237528
TI  - Distribution of pancreatic polypeptide receptors in the rat brain.
AB  - Pancreatic polypeptide (PP) is a regulatory peptide that modulates
      gastrointestinal function. Previously we demonstrated PP receptors in the
      brainstem and interpeduncular nucleus, and the PP receptors in the brainstem
      appear to modulate gastric motility and pancreatic exocrine secretion. The
      purpose of this study is to extend our understanding of the distribution of PP
      receptors in the rat brain in order to determine the systems that are potentially
      modulated by PP. Rat brains were studied using 125I-PP receptor autoradiography
      on cryostat sections of the entire brain cut in three planes (horizontal,
      sagittal, and coronal). Brain regions exhibiting PP binding sites were confirmed
      when identified in all three planes of section. Saturable PP binding was
      identified in the hypothalamus (arcuate and paraventricular n), the rostral
      forebrain (medial preoptic area, anterior olfactory nucleus, islands of Calleja,
      the dorsal endopiriform n, piriform cortex, and the bed n of the stria
      terminalis), medial amygdaloid n; the thalamus (anteromedial thal. n; reuniens
      thal. n; and paraventricular thal n), the interpeduncular red nucleus, substantia
      nigra, parabrachial n; locus coeruleus, mesencephalic trigeminal n, dorsal motor
      n of the vagus, the n solitary tract, and the area postrema. We conclude that PP
      receptors are distributed widely throughout the rat brain. The distribution of
      many of these PP binding sites corresponds to brain regions regulating digestion
      and autonomic function. We speculate, based on the patterns of binding in the
      olfactory and limbic systems, that PP receptors might be involved in positive
      reinforcement of ingestion behavioral as well as modulation of gastrointestinal
      function.

PMID- 9237529
TI  - Amyloid precursor protein accumulates in white matter at the margin of a focal
      ischaemic lesion.
AB  - Amyloid precursor protein (APP) is transported by fast anterograde axonal
      transport. Since disruption of this transport results in APP accumulation, APP
      has been proposed as a sensitive marker of axonal injury. In the present study,
      axonal injury in subcortical white matter and myelinated fibre tracts permeating
      the striatum, 24 h after permanent middle cerebral artery occlusion in the rat,
      has been examined by assessing the location and extent of APP immunoreactivity.
      Increased APP immunoreactivity was present in both areas. This was localised to a
      circumscribed zone immediately adjacent to the boundary of the ischaemic lesion
      in grey matter. The amount of APP immunoreactivity was associated with the volume
      of the ischaemic lesion in individual animals. Increased APP immunoreactivity in
      subcortical white matter and myelinated fibre tracts at the margin of the
      ischaemic zone may prove to be a valuable marker for assessing strategies to
      protect axons after an ischaemic insult.

PMID- 9237531
TI  - Testis-dependent and -independent effects of photoperiod on volumes of song
      control nuclei in American tree sparrows (Spizella arborea).
AB  - Songbirds exhibit seasonal changes in the volumes of song control nuclei. Birds
      on long, spring-like days have larger nuclei than do birds on short, winter-like
      days. The mechanisms mediating volumetric changes have not been determined
      unequivocally, but testosterone (T) is probably involved. This study examined
      whether testicular factors are uniquely responsible for seasonal changes in the
      song system, or whether photoperiod has testis-independent effects. Male American
      tree sparrows were exposed to one of three photoperiodic conditions: (1)
      Photosensitive birds were retained on short days (8L:16D). Plasma T is rarely
      detected in such birds. (2) Photosensitive birds were moved from short days to
      long days (20L:4D) and photostimulated for three weeks. Photostimulation elevates
      circulating T in photosensitive birds. (3) Photorefractory birds were held at
      least four months on 20L:4D. Such birds seldom have detectable levels of T, even
      though they are on long days. In each condition, there were both intact and
      castrated birds. Castration typically removes circulating T in tree sparrows. The
      volumes of the high vocal center (HVC), nucleus robustus archistriatalis (RA),
      and area X were measured. Song nuclei were largest in intact photostimulated
      birds. Other long-day birds (i.e. castrated photostimulated, and intact and
      castrated photorefractory groups) had larger song nuclei than did short-day
      intact or castrated photosensitive birds and did not differ from each other.
      These data indicate that photoperiod has both testis-dependent and -independent
      effects on the volumes of song control nuclei.

PMID- 9237530
TI  - Nitric oxide increases stimulation-evoked acetylcholine release from rat
      hippocampal slices by a cyclic GMP-independent mechanism.
AB  - Nitric oxide (NO) is an endothelium-derived relaxing factor and its main
      mechanism of action is activation of soluble guanylyl cyclase. NO and NO-related
      compounds have been reported to affect several neuronal functions in the central
      nervous system. In this study, we investigated the effects of NO donors (sodium
      nitroprusside (SNP) and (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexenamide (FK409)) on acetylcholine (ACh) release from rat hippocampal slices.
      SNP (10(-5) M) and FK409 (10(-4) M) increased electrical stimulation-evoked ACh
      release without affecting basal release. As dibutyryl cyclic GMP inhibited
      stimulation-evoked ACh release, the effects of these NO donors were not due to
      soluble guanylyl cyclase activation. Atropine increased stimulation-evoked ACh
      release by blocking presynaptic muscarinic autoreceptors, and SNP increased
      stimulation-evoked ACh release in the presence of atropine, suggesting that SNP
      and atropine increase stimulation-evoked ACh release by different mechanisms. The
      present results indicate that NO enhances some part of the excitation-secretion
      coupling pathway without inducing ACh release directly and these effects are
      mediated by cyclic GMP-independent mechanism.

PMID- 9237532
TI  - Neuroprotective effects of the antioxidant LY231617 and NO synthase inhibitors in
      global cerebral ischaemia.
AB  - Recent studies have shown that the novel antioxidant LY231617 protects against
      ischaemia-induced neuronal damage in rat models of global cerebral ischaemia. In
      the present studies we have examined the effects of LY231617 in the gerbil model
      of global cerebral ischaemia. We also examined the effects of four nitric oxide
      synthase inhibitors (3-bromo-7-nitroindazole, N(G)-nitro-L-arginine methyl ester,
      aminoguanidine and S-methylisothiourea sulphate) in this model. LY231617 (50
      mg/kg p.o. or 30 mg/kg i.p.) was administered either 30 min prior to occlusion or
      immediately post-occlusion followed by three further doses at 4, 24 and 48 h
      after the initial dose. 3-Bromo-7-nitroindazole was administered at 40 mg/kg i.p.
      immediately after occlusion followed by 20 mg/kg i.p. at 3, 6, 24 and 48 h, N(G)
      nitro-L-arginine methyl ester was administered at 10 mg/kg i.p. immediately after
      occlusion followed by 5 mg/kg i.p. at 3, 6, 24 and 48 h. Aminoguanidine was
      administered at 80 mg/kg i.p. immediately after occlusion followed by 40 mg/kg
      i.p. at 3, 6, 24 and 48 h and S-methylisothiourea sulphate was administered at 10
      mg/kg i.p. immediately, 3, 6, 24 and 48 h after occlusion. We also examined the
      effects of aminoguanidine administered at 80 mg/kg i.p. immediately after
      occlusion followed by 40 mg/kg i.p. at 3, 6, 24, 48, 72 and 96 h and S
      methylisothiourea sulphate administered at 10 mg/kg i.p. immediately, 3, 6, 24,
      48, 72 and 96 h after occlusion. Control animals were either sham operated or
      subjected to 5 min bilateral carotid occlusion. Extensive neuronal death was
      observed in the CA1 layer of the hippocampus in 5-min bilateral carotid artery
      occluded animals 5 days after surgery. LY231617 provided significant
      neuroprotection against the ischaemia-induced brain damage when administration
      was initiated before or after occlusion (P < 0.05). The neuronal NO synthase
      inhibitors, 3-bromo-7-nitroindazole and a general NO synthase inhibitor, N(G)
      nitro-L-arginine methyl ester also provided significant neuroprotection (P <
      0.05). In contrast aminoguanidine and S-methylisothiourea sulphate (two inducible
      NO synthase inhibitors) failed to protect against the ischaemia-induced brain
      damage. These results indicate that free radicals and nitric oxide are involved
      in ischaemia-induced brain damage following global cerebral ischaemia.
      Antioxidants such as LY231617 or neuronal NO synthase inhibitors can prevent the
      ischaemia-induced neurodegeneration and may be useful as anti-ischaemic agents.

PMID- 9237533
TI  - NMDA induces a biphasic change in intracellular pH in rat hippocampal slices.
AB  - As alterations in intracellular pH (pH(i)) tend to exert a profound effect on the
      properties of cells, this study was undertaken to examine NMDA-induced changes in
      pH(i) in rat hippocampal slices using the BCECF fluorescent technique. The
      'resting' pH(i) in the CA1 pyramidal cell layers was 6.93 +/- 0.07 (mean +/-
      S.D., n = 72 slices) in 25 mM HCO3-/5% CO2-buffered solution at 37 degrees C.
      Exposure of hippocampal slices to NMDA in the range of 10-1000 microM produced a
      biphasic change in pH(i): an initial transient alkaline shift was followed by a
      long-lasting acid shift. Dizocilpine (10 microM) but not CNQX (40 microM) blocked
      the NMDA-induced changes in pH(i). In 0 Ca medium (0 mM Ca2+ supplemented 1 mM
      EGTA, referred to as 0 Ca), pH(i) acid shift caused by NMDA (20 microM) declined
      by about 11%, whereas the initial alkaline shift almost completely disappeared.
      In an independent experiment, the NMDA-induced increase in intracellular Ca2+
      ([Ca2+]i) was reduced by more than 80% in 0 Ca medium. Glucose substitution using
      equimolar pyruvate (as an energy-yielding substrate) suppressed this NMDA-induced
      pH(i) acid shift by two-thirds, while the NMDA-induced pH(i) alkaline shift was
      enhanced. Fluoride (10 mM), a glycolytic inhibitor, abolished NMDA-induced pH(i)
      acid shift. Furthermore, the lactate content of hippocampal slices was markedly
      increased following exposure to NMDA. In conclusion, activation of NMDA receptors
      in rat hippocampal slices evokes a biphasic change in pH(i). The initial alkaline
      shift is suggested to be associated with calcium influx, and the following acid
      shift may be caused by an increase in lactate production through the acceleration
      of glycolysis, as well as the increased [Ca2+]i. The pH(i) acid shift produced by
      the increased lactate may contribute to proton modulation of the NMDA receptor
      and NMDA-induced cell injury or death.

PMID- 9237534
TI  - Effects of subacute lead exposure on [3H]MK-801 binding in hippocampus and
      cerebral cortex in the adult rat.
AB  - We used the NMDA receptor non-competitive antagonist, [3H]MK-801, as a ligand for
      an autoradiographic study to determine the effects of lead on NMDA receptor in
      the rat brain. Adult male rats were administered lead acetate, 100 mg/kg, or
      sodium acetate, 36 mg/kg (control), by i.p. for 7 days. High lead levels were
      detected in blood (41.1 microg/dl) and in brain (16.7-29.4 microg/g).
      Concentrations of lead in brain regions were not significantly different. The
      [3H]MK-801 binding was heterogeneously distributed throughout the rat brain with
      the following order of binding densities: hippocampal formation > cortex >
      caudate-putamen > thalamus > brainstem. Lead exposure produced a significant
      decrease in [3H]MK-801 binding to the NMDA receptor in the hippocampal formation
      including CA2 stratum radiatum, CA3 stratum radiatum, hilus dentate gyrus and
      presubiculum, and in the cerebral cortex including agranular insular, cingulate,
      entorhinal, orbital, parietal and perirhinal areas. The hippocampal formation is
      known as a critical neural structure for learning and memory processes, whereas,
      cortical and subcortical regions have been demonstrated to be involved in the
      modulation of complex behavioral processes. The NMDA receptor has been
      demonstrated to play a key role in synaptic plasticity underlying learning and
      memory. Lead-induced alterations of NMDA receptors in the hippocampal formation
      and cortical areas may play a role in lead-induced neurotoxicity.

PMID- 9237535
TI  - Immunocytochemical analysis of glutamate and GABA in selectively bred mice.
AB  - Withdrawal Seizure Prone (WSP) and Withdrawal Seizure Resistant (WSR) mice have
      been selectively bred for differential ethanol withdrawal handling-induced
      convulsions (HICs). In addition, it has been observed that WSP mice exhibit drug
      naive HICs. This latter finding suggests that WSP and WSR mice differ in their
      susceptibility to HICs. Alterations in the glutamate and gamma-aminobutyric acid
      (GABA) systems have been implicated in convulsive activity and have been proposed
      to underlie the manifestation of ethanol withdrawal symptoms. It is therefore
      possible that WSP and WSR mice are genetically different with respect to their
      glutamatergic and/or GABAergic systems. To test this hypothesis, we have analyzed
      WSP and WSR mice that are both drug- and HIC-naive for differences in the density
      of nerve terminal glutamate and GABA immunoreactivity within the CA1 subfield of
      the hippocampus (CA1) and layer II of the somatosensory cortex (SSC). The major
      finding of this study is that drug- and HIC-naive WSP mice exhibit a
      significantly greater density of presynaptic glutamate immunoreactivity
      associated with asymmetric synapses within the CA1, but not the SSC, when
      compared to WSR mice. The density of GABA immunoreactivity within nerve terminals
      associated with symmetric synapses does not differ between the selected lines in
      either brain region. Since prior drug exposure and HICs cannot account for the
      observed differences in these naive mice, the results strongly suggest that the
      density of nerve terminal glutamate immunoreactivity within the CA1 is a
      reflection of inherent genetic differences between WSP and WSR mice. Furthermore,
      an elevated density of presynaptic glutamate immunoreactivity may be an
      underlying neurochemical correlate to increased susceptibility to drug-naive and
      ethanol withdrawal convulsions.

PMID- 9237536
TI  - Superoxide dismutase partially restores impaired dilatation of the basilar artery
      during diabetes mellitus.
AB  - The goal of this study was to test the hypothesis that administration of
      superoxide dismutase restores nitric oxide synthase-mediated dilatation of the
      basilar artery during diabetes mellitus. We measured the diameter of the basilar
      artery in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg
      i.p.) in response to nitric oxide synthase-dependent agonists (acetylcholine and
      bradykinin) and a nitric oxide synthase-independent agonist (nitroglycerin)
      before and during application of superoxide dismutase. Topical application of
      acetylcholine (1.0 and 10 microM) and bradykinin (1.0 and 10 microM) produced
      dose-related dilatation of the basilar artery in nondiabetic and diabetic rats.
      However, the magnitude of vasodilation produced by acetylcholine and bradykinin
      was significantly less in diabetic rats. Topical application of nitroglycerin
      (0.1 and 1.0 microM) produced similar dose-related dilatation of the basilar
      artery in nondiabetic and diabetic rats. Treatment with superoxide dismutase (150
      U/ml) did not alter baseline diameter of the basilar artery in nondiabetic and
      diabetic rats. However, topical application of superoxide dismutase partially
      restored nitric oxide synthase-dependent dilatation of the basilar artery in
      diabetic rats towards that observed in nondiabetic rats. Superoxide dismutase did
      not alter dilatation of the basilar artery in nondiabetic rats. These findings
      suggest that impaired nitric oxide synthase-dependent dilatation of the basilar
      artery during diabetes mellitus may be related, in part, to enhanced release of
      oxygen-derived free radicals.

PMID- 9237537
TI  - Differential modulation of NMDA-stimulated [3H]dopamine release from rat striatum
      by neuropeptide Y and sigma receptor ligands.
AB  - Although the identity of the endogenous ligands for sigma (sigma) receptors is
      unknown, neuropeptide Y (NPY) has been named as a possible candidate for a
      natural transmitter at these receptors. Using a superfusion system, we compared
      the effect of NPY on NMDA-stimulated [3H]dopamine release in rat striatum to that
      of the sigma agonists (+)-pentazocine and BD737. In contrast to (+)-pentazocine-
      or BD737-mediated inhibition of release, NPY enhanced release. However, the same
      sigma antagonists (BD1008, DuP734, haloperidol and DTG) that reverse (+)
      pentazocine- or BD737-mediated inhibition, as well as a Y receptor antagonist,
      PYX-1, all reversed the enhancement. PYX-1 also reversed the (+)-pentazocine- and
      BD737-mediated inhibition of release. Peptide YY (PYY) and [Leu31,Pro34]NPY did
      not mimic the effect of NPY. NPY13-36 enhanced release to the same extent as NPY
      but the effect was not reversed by sigma antagonists. Our findings are consistent
      with the potential role of NPY as an endogenous ligand for a subtype of sigma
      receptor with characteristics different from Y1, Y2 and Y3 receptors but
      sensitive to PYX-1.

PMID- 9237539
TI  - Synergistic effects of cocaine and dizocilpine (MK-801) on brain stimulation
      reward.
AB  - The rewarding effects of lateral hypothalamic electrical stimulation were
      assessed in animals treated with the combination of cocaine and dizocilpine (MK
      801), a noncompetitive N-methyl-D-aspartate antagonist. Eight male Long-Evans
      rats were trained to perform a lever-press operant to deliver trains of cathodal
      rectangular pulses directly into the lateral hypothalamus. Response rate was
      determined across the range of effective stimulation frequencies. For each rat
      the frequency threshold was defined as the lowest frequency that sustained
      minimal responding. After thresholds had stabilized each rat was tested under 4
      treatment conditions; saline + saline, dizocilpine (0.05 mg/kg, i.p., 30 min
      before test) + saline, saline + cocaine (4 mg/kg, i.p., 5 min before test) and
      dizocilpine + cocaine. The saline + saline, dizocilpine + saline and saline +
      cocaine treatments each failed to cause significant changes in threshold or
      maximum response rates. The dizocilpine + cocaine treatment produced a large
      reduction in thresholds indicating a synergism between the two drugs and the
      rewarding stimulation. These synergistic effects of dizocilpine and cocaine stand
      in contrast to the putative antagonism by dizocilpine of cocaine's psychomotor
      sensitizing action.

PMID- 9237538
TI  - The effects of different stressors on extracellular 5-hydroxytryptamine and 5
      hydroxyindoleacetic acid.
AB  - The effects of application of five different stressors on extracellular 5
      hydroxytryptamine and 5-hydroxyindoleacetic acid in the striatum and hippocampus
      were compared using in vivo microdialysis. Forced swimming for 30 min elevated
      extracellular 5-hydroxytryptamine to 90% above basal levels and reduced 5
      hydroxyindoleacetic acid to 45% of basal levels in the striatum during the swim
      session. In contrast, hippocampal 5-hydroxytryptamine was not altered
      significantly by forced swimming but 5-hydroxyindoleacetic acid levels were
      reduced to 60% of basal levels. Tail pinch for 5 min elevated 5-hydroxytryptamine
      to 55% above basal levels in striatum and to 35% above basal levels in
      hippocampus. Tail pinch had no effect on 5-hydroxyindoleacetic acid in either
      brain region. In contrast to forced swimming and the tail pinch, the other three
      stressors, immobilization stress for 100 min, exposure to a cold environment (4
      degrees C) for 2 h, and forced motor activity on a rotarod for 30 min, failed to
      alter extracellular 5-hydroxytryptamine in either the striatum or the
      hippocampus. All five stressors increased plasma corticosterone levels: tail
      pinch, 246%; cold stress, 432%; immobilization, 870%; forced motor activity,
      1030%; and forced swimming, 1530%. These results suggest that individual
      stressors produce different effects on extracellular 5-hydroxytryptamine in
      different brain regions. In addition, there does not appear to be a relationship
      between the effects of stressors on the 5-hydroxytryptamine system and the
      magnitude of their ability to activate the hypothalamic-pituitary-adrenal axis.

PMID- 9237540
TI  - Chronic paroxetine desensitises 5-HT1D but not 5-HT1B autoreceptors in rat
      lateral geniculate nucleus.
AB  - The present study examined the effect of chronic paroxetine (10 mg/kg p.o., 21
      days) on the 5-HT1B and 5-HT1D autoreceptors controlling 5-HT efflux in slices of
      rat ventrolateral geniculate nucleus. Electrically stimulated 5-HT efflux (10
      pulses, 200 Hz, 0.1 ms, 10 mA) was measured using fast cyclic voltammetry. Peak 5
      HT efflux was greater (P < 0.01) after chronic paroxetine (22.2 +/- 1.4 nM, mean
      +/- S.E.M.) than water (15.8 +/- 1.4 nM). 5-HT efflux was inhibited by CP 93129
      (1 nM-10 microM) and sumatriptan (1 nM-1 microM), agonists at 5-HT1B and 5-HT1D
      receptors, respectively. Chronic paroxetine did not affect the sensitivity of the
      5-HT1B autoreceptor but shifted the sumatriptan concentration-response curve to
      the right (P < 0.05). These data suggest that chronic paroxetine increases evoked
      5-HT efflux. This may be the result of desensitisation of 5-HT1D but not 5-HT1B
      autoreceptors.

PMID- 9237541
TI  - Characterization, distribution and lateralization of baroreceptor-related neurons
      in the rat insular cortex.
AB  - The insular cortex contains a site of cardiovascular representation. Stimulation
      experiments suggest a discrete localization within the rostral posterior insula.
      In 34 urethane-anesthetized male Sprague-Dawley rats, we investigated whether
      cells responsive to baroreceptor stimulation with phenylephrine and sodium
      nitroprusside were selectively clustered within the insula compared with the
      surrounding frontoparietal cortex, the extent of distribution of these responsive
      cells within the insula, and whether there was any lateralization of response. In
      addition, we characterized the cells as SE (sympathoexcitatory), SI
      (sympathoinhibitory) or null cells using the criteria of Barman. Of the 128
      insular cells investigated with extracellular recording techniques, 70% responded
      to baroreceptor manipulations compared to 32% of the 57 cells investigated
      outside the insula (P < 0.0001). The majority of the responsive cells were SE
      units and were distributed widely throughout the insular cortex including
      anterior areas not previously thought to be involved in cardiovascular control.
      Within the rostral posterior insula from which cardiovascular effects are mainly
      obtained in stimulation experiments, lateralization was identified, with
      significantly more cells responding to blood pressure changes being found within
      the right posterior insula than the left (P < 0.003). These data confirm the
      importance of the right posterior insula in the rat as a site of cardiovascular
      representation; identify a more extensive distribution of cells responsive to
      blood pressure changes within the insula than previous studies and imply more
      widespread convergence of visceral afferent information within the insula.

PMID- 9237542
TI  - Activity of single action potentials in monkey motor cortex during long-term task
      learning.
AB  - Studies using continuous recording of neural activity during long-term learning
      are now possible with an implanted neurotrophic electrode. During recording of
      individual cortical action potentials in monkeys performing a reach and grasp
      task, we were able to follow the gradual change in firing of several action
      potentials as the task was learned. Control experiments suggest that the neurons
      involved in the learning were initially silent.

PMID- 9237543
TI  - Factors produced by activated macrophages reduce accumulation of Alzheimer's beta
      amyloid protein in vascular smooth muscle cells.
AB  - Smooth muscle cells (SMCs) isolated from amyloid-angiopathy affected brain
      vessels accumulate intracellularly amyloid-beta peptide (A beta). Now we
      demonstrate that accumulation of A beta in SMCs can be reduced by factors
      secreted by macrophages - IL-1alpha, IL-6, TNF-alpha, TGF-beta1 or PGE2 -
      probably by stimulating the non-amyloidogenic processing of A beta precursor
      protein (PP). It is suggested that brain macrophages may regulate A betaPP/A beta
      metabolism under physiological conditions and prevent beta-amyloidosis. The
      disturbance of this regulatory function of brain macrophages may result in
      excessive production and accumulation of A beta.

PMID- 9237544
TI  - Firing rate dependent effect of cocaine on single neurons of the rat lateral
      striatum.
AB  - Cocaine's effects on striatal neurons related to vertical head movement were
      studied during a task requiring vertical head movement. The proportion of long
      distance head movements was increased by low doses but decreased by the high
      dose, which produced stereotypic head bobbing. At all doses, normally low firing
      rates related to movement were elevated to a greater degree than were normally
      high firing rates. At the high dose, normally high firing rates were strongly
      suppressed, a restriction which may contribute to the decreased behavioral
      diversity characteristic of stereotypy.

PMID- 9237545
TI  - Paroxysmal discharges in the EL mouse, a genetic model of epilepsy.
AB  - The EL/Suz (EL) mouse is a strain that is highly susceptible to convulsive
      seizures after repeated sensory stimulation. Its control strain, DDY/Jc1 (DDY),
      is less susceptible under similar conditions. The seizure prone phenotype is the
      result of differences at several genetic loci. In vivo electrical recordings from
      the seizure prone EL mouse brain have shown that the appearance of abnormal
      discharges in the hippocampus are critical to the onset of generalized seizures,
      indicating that the hippocampus plays an important role in EL mouse seizure
      activity. In the present study, electrophysiological differences between EL and
      DDY mice (9-15 weeks of age) were examined by comparing field potentials recorded
      from the dentate granule cell layer of hippocampal brain slices from mice that
      had not been stimulated to induce seizures. In control physiological solution, no
      significant differences were observed in characteristics of perforant path evoked
      field potentials or in paired pulse depression of evoked field potentials using
      20 to 300 ms interstimulus intervals. After 60 min of disinhibition following
      bicuculline (10 microM) exposure, however, prolonged large amplitude potentials,
      paroxysmal discharges, were evoked by perforant path stimulation in the dentate
      gyrus of EL mice but were absent in the DDY strain. Paroxysmal discharges were
      curtailed by APV and were similar to responses recorded from the dentate gyrus in
      hippocampal brain slices from temporal lobe epileptic patients. The field
      response to hilar stimulation was identical in both strains and was composed of a
      single population spike before and after bicuculline exposure. Mossy fiber
      terminals were not present in the molecular layer of either strain. We propose
      that the mechanisms leading to a greater likelihood of paroxysmal discharge
      generation in EL mouse may be important in the development and/or generation of
      epileptic seizures in this mouse strain and may be a significant phenotypic
      difference between the EL mouse and its parent strain.

PMID- 9237546
TI  - The pedunculopontine tegmental nucleus issues collaterals to the fastigial
      nucleus and rostral ventrolateral reticular nucleus in the rat.
AB  - The pedunculopontine-laterodorsal tegmental nuclear complex was identified as a
      major source of brainstem afferents terminating in the fastigial cerebellar
      nucleus and/or ventrolateral reticular nucleus (n.Rvl). Collaterals from the
      pedunculopontine nucleus (Ch5 area) to rostral [vasopressor] regions of the
      fastigial nucleus and ventral reticular formation were revealed with a combined
      retrograde tracing technique. The data implicate acetylcholine as a transmitter
      and raise the hypothesis that the identified afferents may contribute to the
      autonomic and behavioral responses to midline cerebellar stimulation.

PMID- 9237547
TI  - Flow-cytometric analysis on kainate-induced decrease in the cellular content of
      non-protein thiols in dissociated rat brain neurons.
AB  - In order to study the kainate-induced oxidative stress on brain neurons, the
      effect of kainate on cellular content of glutathione in rat cerebellar neurons
      were examined using a flow cytometer and 5-chloromethylfluorescein, a fluorescent
      dye for cellular non-protein thiols (mainly glutathione). Kainate at
      concentrations ranging from 30 microM to 1 mM produced a dose-dependent decrease
      in cellular content of glutathione. Exposure of neurons to kainate at
      concentrations of 300 microM or greater seemed to deplete cellular glutathione.
      Potency of kainate in reducing cellular content of glutathione was greater than
      those of glutamate and N-methyl-D-aspartate (NMDA). Kainate-induced decrease in
      cellular content of glutathione was partly attenuated by 6-nitro-7-cyano
      quinoxaline-2,3-dione, a blocker of non-NMDA receptors and removal of external
      Ca2+. Results indicate that kainate causes Ca2(+)-dependent oxidative stress that
      decreases the cellular content of glutathione via activation of non-NMDA type of
      glutamate receptors.

PMID- 9237548
TI  - Light and electron microscopic immunocytochemical visualization of 5-HT1B
      receptors in the rat brain.
AB  - Specific antipeptide antibodies were used for the immunohistochemical
      visualization of 5-HT1B receptors in the rat brain. A dense, specific 5-HT1B
      receptor-like immunoreactivity was found in the globus pallidus, the dorsal
      subiculum and the substantia nigra. At the light microscope level, immunostaining
      was diffuse within the neuropil but absent from cell bodies. Observations at the
      electron microscope level in the substantia nigra showed immunoperoxidase
      staining in fine unmyelinated axons and nerve terminals.

PMID- 9237549
TI  - Expression of dopamine D2 receptor mRNA isoforms in the carotid body of rat, cat
      and rabbit.
AB  - Using the Reverse transcription-Polymerase chain reaction, we detected dopamine
      D2 receptor mRNA short and long isoforms in the adult carotid body of rats, cats,
      and rabbits. For these animals, the relative short/long ratios were 0.60, 0.65
      and 0.57, respectively. Our results suggest that the variety of dopamine effects
      on carotid chemoreceptor activity, that has been related to species differences,
      may not be dependent on the expression levels of the dopamine D2 receptor mRNA
      isoforms in the studied species.

PMID- 9237550
TI  - Norepinephrine transmitter metabolite induces apoptosis in differentiated rat
      pheochromocytoma cells.
AB  - 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the monoamine oxidase A metabolite
      of norepinephrine and epinephrine. DOPEGAL, but not other metabolites, kills
      differentiated PC-12 cells. However, the type of DOPEGAL induced cell death,
      whether necrosis or apoptosis, is not known. To determine the type of cell death
      triggered by DOPEGAL, PC-12 cells cultured in the presence or absence of 30
      microM DOPEGAL were examined by electron microscopy and DNA agarose gel
      electrophoresis for characteristic features of apoptosis. Results indicate that
      DOPEGAL induces apoptosis in these cells. Implications for degenerative diseases
      are discussed.

PMID- 9237551
TI  - Substance P releases and augments the morphine-evoked release of adenosine from
      spinal cord.
AB  - The effects of substance P on the morphine-evoked release of adenosine were
      examined. Substance P alone produced a multiphasic effect on release of
      adenosine, with release occurring at low nanomolar concentrations and at a
      micromolar concentration, but not at intermediate concentrations. An inactive
      dose of substance P augmented the morphine-evoked release of adenosine at a
      nanomolar concentration of morphine. Release of adenosine by substance P alone (1
      nM) or substance P/morphine (100 nM/10 nM) was Ca2(+)-dependent and originated
      from capsaicin-sensitive nerve terminals.

PMID- 9237552
TI  - Iron deposits in multiple sclerosis and Alzheimer's disease brains.
AB  - Iron may contribute to the pathogenesis of neurological diseases by promoting
      oxidative damage. The localization of iron in multiple sclerosis (MS) and
      Alzheimer's disease (AD) brains was investigated to further the understanding of
      its pathogenic role in these disease states. Earlier studies, utilizing a
      standard Perls' stain, yielded conflicting reports regarding the distribution of
      iron deposits in MS brains, and a previous study on AD brains utilized a
      diaminobenzidine (DAB) enhanced version of this stain. In the present study, a
      modified version of the DAB-enhanced stain was used; it utilizes sodium
      borohydride, proteinase K, Triton X-100 and xylenes to increase the accessibility
      of tissue iron to histochemical reagents. This modified method can reveal iron
      deposits that are missed by the Perls' or DAB-enhanced Perls' stains. In addition
      to its normal deposition in oligodendrocytes and myelin, iron was detected in
      reactive microglia, ameboid microglia and macrophages in MS brains. In AD brains,
      three types of plaques were stained: dense core, clear core and amorphous
      plaques. Punctate staining was also observed in neurons in the corticies of AD
      brains. The structure accounting for punctate labeling may be damaged
      mitochondria, lipofuscin or amyloid deposits. Dense core plaques, clear plaques
      and punctate labeling were not detected in the previous AD study which utilized
      only the DAB-enhanced Perls' stain. The labeling of these additional structures
      illustrates the benefit of the modified method. In summary, the localization of
      iron deposition in MS and AD brains indicates potential sites where iron could
      promote oxidative damage in these disease states.

PMID- 9237553
TI  - A set of electrophoretic molecular markers for strain typing and population
      genetic studies of Histoplasma capsulatum.
AB  - A set of eleven biallelic and three multiallelic molecular markers have been
      developed to analyze populations of Histoplasma capsulatum. All markers are
      amplified by polymerase chain reaction (PCR) and can be readily scored using
      minimal amounts of template DNA. The 11 biallelic loci have polymorphic
      restriction endonuclease sites or small insertions or deletions which may be
      assessed by agarose gel electrophoresis. These markers are inherited in an
      unambiguous manner and are ideal for assessing structure and gene flow within US
      populations of H. capsulatum, but are monomorphic in non-US populations. Both
      length and sequence variation are present in the multiallelic loci, which can be
      scored by direct sequencing, polyacrylamide gel electrophoresis, or single-strand
      conformation polymorphism (SSCP): As they are hypervariable, the multiallelic
      loci can be used to type isolates and to assess the level of genetic variation
      within populations. Preliminary results indicate that the three multiallelic
      markers presented are sufficient to distinguish isolates at the individual level
      and are polymorphic in both US and non-US populations. This collection of
      molecular markers will be a useful tool in population and epidemiology studies of
      H. capsulatum.

PMID- 9237554
TI  - Analysis of the binding of deoxyribonuclease I to G-actin by capillary
      electrophoresis.
AB  - Deoxyribonuclease I (DNase I) is an actin monomer-sequestering actin binding
      protein (ABP) that inhibits the rate and extent of actin polymerisation in vitro
      by forming a high affinity, stoichiometric 1:1 complex. Using capillary zone
      electrophoresis (CZE), we have studied the interaction between G-actin and DNase
      I to evaluate the capability of CZE to determine the dissociation constant (K(d)
      value) for this interaction. We used (i) an uncoated fused-silica capillary and
      ultraviolet (UV) detection at 214 nm; (ii) a hydrophilic-coated capillary with UV
      detection at 214 nm; and (iii) a hydrophilic-coated capillary with laser-induced
      fluorescence (LIF) detection. Using procedure (ii), a K(d) value of approximately
      0.03 microM was obtained by simulation of binding data. We conclude that CZE
      combined with a LIF detector has the capacity to extend the determination of K(d)
      values from the micromolar range to the nanomolar range. Subsequent determination
      of K(d) values for other actin-binding proteins should provide information on
      interactions between the binding sites on actin for these proteins and their
      spatial relationship.

PMID- 9237555
TI  - The serine proteinase inhibitory proteins of the chondrodystrophoid (beagle) and
      non-chondrodystrophoid (greyhound) canine intervertebral disc.
AB  - Trypsin inhibitory proteins of low buoyant density (p < or = 1.35 g/mL) fractions
      were prepared by CsCl density gradient ultracentrifugation of 4 M guanidinium
      hydrochloride extracts of lumbar beagle and greyhound annulus fibrosus and
      nucleus pulposus from animals aged 1 to 6 years. Affinity blotting with
      biotinylated trypsin was used to identify active trypsin inhibitory protein
      species; these species were also identified immunologically by Western blotting
      using antibodies against bovine pancreatic trypsin inhibitor (BPTI), and human
      inter-alpha-trypsin inhibitor (ITI). None of the trypsin inhibitory species
      evident in Western blots were reactive with anti-human alpha1-proteinase
      inhibitor (alpha-1-PI), alpha2-macroglobulin or secretory leucocyte proteinase
      inhibitor. The greyhound intervertebral disc samples generally had higher levels
      of active trypsin inhibitor species per unit weight of tissue extracted, and a
      more extensive range of inhibitor species. Inhibitor species of 30, 32, 34 kDa
      were identified in both beagle and greyhound intervertebral disc samples; these
      species were generally most prominent in the annulus fibrosus samples. In
      contrast, the nucleus pulposus samples contained relatively large trypsin
      inhibitor species; the anti-BPTI detected an inhibitor species of approximately
      85-90 kDa; anti-ITI detected species of 120-250 kDa; biotinylated trypsin
      detected species of 60-110 kDa. A small molecular mass trypsin inhibitor species
      of 6 kDa, which was of similar mobility to BPTI, was also detected in annulus
      fibrosus samples; however, this species did not react with anti-BPTI.

PMID- 9237556
TI  - Electrophoretic characterisation of fractions collected from gluten protein
      extracts subjected to size-exclusion high-performance liquid chromatography.
AB  - The electrophoretic analysis by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE; reduced and unreduced) of fractions, collected from a
      size exclusion-high performance liquid chromatography (SE-HPLC) separation of
      gluten proteins using a column with pore size of around 400A, showed clear
      resolution for the seven elution ranges studied in two Australian bread wheat
      lines. Polymeric proteins - high molecular weight (HMW) glutenin subunits, low
      molecular weight (LMW) glutenin subunits, HMW albumins and some modified omega
      gliadins - appeared exclusively in the region within the first peak of the
      chromatogram (fractions 1 to 5), the limit being a region that resolved as a
      small peak before the large peak of gliadins and where some omega-gliadins
      eluted. A larger proportion of HMW glutenin subunits and B subunits contributed
      to polymer formation of higher molecular weight. The polymer size decreased as
      the proportion of the other protein components increased.

PMID- 9237557
TI  - A role for Edman degradation in proteome studies.
AB  - Advances in protein database design and the software used to access the sequence
      data has led to progress in using protein attributes such as amino acid
      composition and peptide masses to identify proteins separated by two-dimensional
      electrophoresis. However, Edman degradation remains the principal technique for
      protein identification and it presents a significant bottleneck in the progress
      towards rapid protein identification. Simple modifications to the sequencing
      hardware, which automate the delivery of protein spots into the sequencer, and
      parallel sequencing of the protein spots represent a significant advance in the
      use of Edman degradation to rapidly generate the powerful protein attribute, an N
      terminal sequence tag.

PMID- 9237558
TI  - Identification of wallaby milk whey proteins separated by two-dimensional
      electrophoresis, using amino acid analysis and sequence tagging.
AB  - Micropreparative two-dimensional polyacrylamide gel electrophoresis has been used
      to separate milk whey proteins from the Tammar wallaby (Macropus eugenii). We
      have used a combination of amino acid analysis and N-terminal sequence tagging as
      a rapid and sensitive method to identify the major whey proteins. Using these
      techniques, we confidently identified alpha-lactalbumin and late lactation
      protein. While these are the only two M. eugenii whey proteins with a
      corresponding SWISS-PROT entry, we demonstrate that by using amino acid analysis
      and matching across species boundaries, we can identify previously unsequenced
      conserved wallaby whey proteins including beta-lactoglobulin and serum albumin.

PMID- 9237559
TI  - Two-dimensional gel electrophoresis of actin-binding proteins isolated by
      affinity chromatography from human skeletal muscle.
AB  - In muscle cells actin exists as a mixture of monomeric (G-actin) and filamentous
      actin (F-actin) and ionic conditions strongly favor the formation of F-actin. The
      existence of unpolymerized actin depends, among other factors, on proteins that
      bind to G-actin, the so-called G-actin-binding proteins (G-ABPs). We have coupled
      monomeric actin to divinylsulphone-activated agarose (Mini-Leak) to isolate G
      ABPs in human skeletal muscle. Eluted proteins were analyzed by two-dimensional
      gel electrophoresis (2-DE), which shows that some proteins are selectively
      retained. Deoxyribonuclease I (DNase I) is known to bind residues at the "pointed
      end" of actin (subdomains 2 and 4) with a high affinity. When DNase I is bound to
      the actin Mini-Leak before applying the skeletal muscle extract, the 2-DE gels of
      the eluted proteins reveals differences when compared to gels of proteins eluted
      from actin-Mini-Leak and DNase I-Mini-Leak affinity columns. This strategy should
      detect ABPs which bind to sites other than the DNase I-binding site and some may
      prove to be novel.

PMID- 9237560
TI  - Separation of tumor necrosis factor alpha isoforms by two-dimensional
      polyacrylamide gel electrophoresis.
AB  - The mouse macrophage cell-line RAW264.7, stimulated with lipopolysaccharide, was
      used as a model for the study of the production of tumor necrosis factor (TNF)
      isoforms. TNF is synthesised initially as a 26 kDa transmembrane precursor, which
      is then processed enzymatically by a protease to release a mature molecule of 17
      kDa. Dose-dependent production of transmembrane TNF was assessed by fractionation
      of cell membranes and Western blot analysis followed by autoradiography and
      densitometry. Isoforms of both the precursor and mature molecules were separated
      using two-dimensional (2-D) electrophoresis with immobilised pH gradient 3-10
      linear gels as the first dimension. After radiolabelling of cells with 35S, both
      cell-associated and supernate-associated TNF isoforms were immunoprecipitated. A
      large number of protein spots were visualised on the 2-D gel map, for both the
      transmembrane and mature TNF species, more than have been detected previously
      using one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      (SDS-PAGE). The likelihood that these putative isoforms were the result of
      differential glycosylation was tested by preincubating the cells with
      tunicamycin. This had the effect of reducing the number of protein spots, notably
      the higher molecular weight species. There were a number of precursor TNF
      isoforms that were unchanged upon tunicamycin treatment and these presumably
      reflect protein modifications other than glycosylation.

PMID- 9237561
TI  - Models of mobility-shift assay of complexes between dimerizing protein and DNA.
AB  - The theory of mass transport coupled to macromolecular interactions under
      chemical kinetic control forms the basis of four different models of the
      electrophoretic mobility-shift assay of complexes formed between dimerizing
      proteins and DNA. The theory of mass action was applied to the set of
      simultaneous dimerization (either simple or ligand-induced) and DNA-binding
      reactions in order to fix the initial equilibrium composition of mixtures to be
      assayed. Theoretical mobility-shift patterns were obtained for a range of protein
      concentrations at constant DNA concentration by numerical solution of the set of
      simultaneous transport-reaction equations appropriate for each model. In those
      cases in which dimerization in solution is modeled (including
      heterodimerization), analysis of the peaks in the patterns provides apparent
      binding constants, which, when extrapolated to infinite dilution of protein,
      yield acceptable estimates of equilibrium constants. Those for binding of dimer
      are products of two or three equilibrium constants, from which the equilibrium
      binding constant can be extracted, provided that dimerization and, where
      required, ligand-binding constants are determined by independent physicochemical
      methods. Dimerization of protein when bound to DNA is distinctive in that
      extrapolation to infinite dilution of protein is not required.

PMID- 9237562
TI  - Applications of consensus polymerase chain reaction with subsequent
      electrophoretic distinction of amplificates.
AB  - Conserved sequences within gene families permit the design of consensus primers
      that match several members of a given class of homologous genes. Polymerase chain
      reaction (PCR) products obtained with such consensus primers were characterized
      by restriction mapping or single-strand conformation polymorphism (SSCP)
      analysis, using precast polyacrylamide minigels and automated silver staining.
      Examples for the electrophoretic distinction of consensus amplificates are
      presented in the fields of guanylyl cyclase expression studies and in the
      determination of B-cell clonality in human blood samples. Guanylyl cyclase
      expression in inner ear tissues of guinea pigs was investigated by reverse
      transcription PCR using consensus primers with specificity for the subclass of
      particulate guanylyl cyclases. The resulting PCR products were assigned to three
      representatives of this group by restriction mapping. The consensus PCR approach
      enabled the detection of an unexpected receptor type, namely guanylyl cyclase C,
      in the inner ear. The distinction by SSCP analysis of denatured consensus
      amplificates was appropriate for the identification of clone-specifically
      rearranged immunoglobulin heavy chain genes of B-lymphocytes. Genomic DNA
      isolated from blood samples of leukemia patients served as the template for the
      consensus amplification of clone-specific VDJ rearrangements. Rapid distinction
      and re-identification of consensus PCR products was achieved by SSCP analysis for
      regular antigen receptor rearrangements and for t(14; 18) translocations. The
      potential of these procedures for detecting leukemia or lymphoma clones when
      monitoring minimal residual disease was assessed.

PMID- 9237563
TI  - A simple and fast procedure for high quality DNA isolation from gels using
      laundry detergent and inverted columns.
AB  - A quick method for the recovery of DNA from agarose and polyacrylamide gels with
      high efficiency and quality is described. Excised gel slices, containing at least
      10 ng DNA, are incubated for 15 min at 60 degrees C in the presence of laundry
      detergents. An "inverted column" is obtained by covering the extraction liquid by
      a layer of cotton wool, Sephadex G-50 and another layer of cotton wool. Following
      centrifugation the supernatant containing the DNA is recovered by aspiration and
      the DNA is precipitated with isopropanol and tRNA, washed with ethanol and air
      dried. The yield of reisolated DNA does not depend on DNA fragment size and small
      quantities of gel volume. Thus, the technique may prove useful in a broad range
      of applications in the methodology of molecular biology.

PMID- 9237564
TI  - Polymorphism of 5' of the catalase gene in Hungarian acatalasemia and
      hypocatalasemia.
AB  - The amplified fragment length polymorphism of Hinf1 on the promoter region of the
      catalase gene in Hungarian acatalasemic and hypocatalasemic patients yielded
      three different patterns with five bands in total. The sequence analyses revealed
      A-to-T, C-to-A, and C-to-T mutations at positions -21, -20, and -18 upstream of
      the translational initiation site. The -21 A-to-T mutations were more frequent in
      acatalasemic and hypocatalasemic patients (36/2) than in controls (18/14). This
      mutation had been detected in Japanese acatalasemic patients while the other two
      are novel mutations. Two extra bands in the Hinf1 pattern are due to star-like
      activity that cleaved a G/ATTT sequence at position -4 to 0 upstream of the
      initiation site.

PMID- 9237565
TI  - Cellular electrophoretic mobility data: a first approach to a database.
AB  - Cellular electrophoretic mobility values of 288 types of eucaryotic cells were
      collected from literature published worldwide by a series of authors during the
      past forty years and arranged in a list. This list contains well-known recent
      electrophoretic results and also data that cannot be found anymore with modern
      literature retrieval systems. It will be a valuable help for scientists trying to
      purify cell populations. In addition, it confirms the observation that most
      eucaryotic cells have very similar electrophoretic mobilities, ranging from 40%
      above to 50% below the electrophoretic mobility of human erythrocytes, and thus
      reinforces the suggestion that electrophoretic mobilities of eucaryotic cells are
      subjected to strong biological controls.

PMID- 9237566
TI  - Identification and classification of autoantibody repertoires (Western blots)
      with a pattern recognition algorithm by an artificial neural network.
AB  - The screening of sera for autoantibodies with Western blots reveals complex
      repertoires. the compostion of such repertoires depends on genetic control of
      autoantibody-producing cells, the individual's history of exposure to its own and
      to foreign antigens, and also on the presence of autoimmune diseases. Our method
      shows how staining patterns of Western blots can be recoded as binary or grey
      value vectors. Vectors are transferred to artificial neural networks for
      learning. Artificial neural networks are able to recognize group-specific
      antibody binding patterns. Staining patterns can be attributed to diagnostic
      groups. This may support diagnostic procedures.

PMID- 9237567
TI  - The resolution between two native proteins and between their sodium dodecyl
      sulfate-complexes in agarose and polyacrylamide gel electrophoresis.
AB  - Commercial gel electrophoresis apparatus with intermittent fluorescence scanning
      of the migration path (HPGE-1000 apparatus, LabIntelligence) makes it possible to
      measure band width and migration distance as a function of the duration of
      electrophoresis. As a result, resolution can be evaluated quantitatively and
      therefore different gel media can be compared objectively. The resolution of
      fluorescein carboxylate labeled conalbumin (molecular mass 86 kDa) and soybean
      trypsin inhibitor (22.7 kDa) in gel electrophoresis was found to increase as a
      function of the gel type in the order SeaKem GTG-, SeaKem Gold-agarose, 2% N,N'
      methylenebisacrylamide cross-linked polyacrylamide, MetaPhor-XR-, and SeaPrep
      agarose. The advantage in resolving capacity of SeaPrep agarose over the
      polyacrylamide gel was by a factor of up to five. The resolving capacity of the
      agaroses was in indirect relation to the degree of electroendosmosis. In all
      media, resolution increased with migration distance (time). The same proteins
      when reacted with sodium dodecyl sulfate (SDS) resolve (i) better at up to 6%
      SeaPrep agarose concentration than in polyacrylamide, as in the gel
      electrophoresis of the native proteins; (ii) less effectively, by contrast, at
      SeaPrep agarose concentrations > 6%, than in polyacrylamide gel; and (iii)
      significantly better in 4-6% SeaPrep agarose than in 4-6% SeaKem GTG agarose.
      Since Ferguson plot analysis in both agarose and polyacrylamide gels shows that
      the two SDS-proteins are larger than the native proteins with which they are
      complexed, the superiority of polyacrylamide gels above 7% appears to be
      correlated with the fact that its mean pore radius, estimated for both media
      using identical assumptions and identical rigid spherical standards - proteins,
      is approximately seven times larger than that of SeaPrep agarose in the
      concentration range of 3-8%, and that therefore the molecular "fit" in
      polyacrylamide is closer than that in SeaPrep agarose of the concentration range
      used. The dependence of resolution on the ratio of particle radius to mean pore
      radius ("fit") is also suggested by the fact that the two SDS-proteins resolve in
      a biphasic dependence on gel concentration in both agarose and polyacrylamide,
      with a maximum at 6% agarose and 10% polyacrylamide.

PMID- 9237568
TI  - Oriented macroporous polyacrylamide gels.
AB  - Macroporous gels with huge cavities and partition walls result from controlled
      microsyneresis during gelation. In this report we show that the microsyneresis
      process can be further controlled: it is possible to orient the partition walls
      of macropores by the use of an electric field throughout polymerization. Our
      oriented macroporous polyacrylamide gels offer a specific structure: a set of
      parallel channels of about 2 microm inner diameter, with polyacrylamide walls
      including acidic groups linked to the aggregated matter.

PMID- 9237569
TI  - Multistructure sequencing of N-linked fetuin glycans by capillary gel
      electrophoresis and enzyme matrix digestion.
AB  - Oligosaccharide sequencing by specific enzymatic digestion of N-linked fetuin
      glycans using a carefully designed exoglycosidase matrix in conjunction with
      separation of the combined digests by high performance capillary gel
      electrophoresis is described. Due to the extremely high separation power and
      excellent reproducibility of capillary gel electrophoresis, in most instances no
      isolation of the individual oligosaccharides is necessary, enabling
      multistructure sequencing from a released glycan pool. By comparing the positions
      of the separated exoglycosidase digest fragments to maltooligosaccharides of
      known size, relative migration times and migration shifts are easily calculated.
      Hence, the particular sequence of each oligosaccharide in a released glycan pool
      can be proposed with high confidence. Additionally, with the use of high
      sensitivity laser-induced fluorescence detection, complete sequence information
      can be attained from picomolar amounts of purified glycoproteins.

PMID- 9237570
TI  - Fast separation of underivatized carbohydrates by coelectroosmotic capillary
      electrophoresis.
AB  - A method for the rapid quantitative analysis of underivatized acidic sugars,
      monosaccharides and disaccharides using coelectroosmotic capillary
      electrophoresis was developed. Indirect UV detection at 254 nm using sorbate as
      background electrolyte was employed for monitoring the analytes. A highly
      alkaline pH value of the electrolyte system was chosen in order to achieve an
      electrophoretic mobility of the saccharides towards the anode. A dynamic reversal
      of the electroosmotic flow and, by this means, a codirectional movement of the
      negatively charged analytes and the electroosmotic flow is accomplished by
      employing a polycationic surfactant (hexadimethrine bromide), which is added to
      the background electrolyte. To further improve the resolution of specific
      carbohydrates, acetone is used as organic modifier. A practical application of
      the developed method for the fast determination of fructose, glucose, and sucrose
      in various soft drinks is provided.

PMID- 9237571
TI  - Separation of disaccharides as their borate complexes by capillary
      electrophoresis with indirect detection in visible range.
AB  - Borate complexation was used to make possible the separation of disaccharides by
      capillary electrophoresis with indirect detection. A high borate concentration
      did not affect the indirect detection sensitivity in as negative a way as
      predicted previously. The concentration sensitivity for sucrose was determined to
      be 2 mM at the borate concentration of 200 mM in running electrolyte. The newly
      introduced background [corrected] chromophore, p-nitrophenol, allows the
      monitoring of the separation process in a visible range at 400 nm. This also
      enables the indirect detection of UV-absorbing compounds in complex mixtures in
      which they would be impossible to detect with a UV-absorbing background
      [corrected] chromophore.

PMID- 9237572
TI  - The effect of column length, applied voltage, gel type, and concentration on the
      capillary electrophoresis separation of DNA fragments and polymerase chain
      reaction products.
AB  - This work examines the effect of different parameters on migration time,
      resolution, and speed of analysis of DNA fragments and PCR products. These
      parameters include column length, applied voltage, gel type and concentration,
      and buffer ionic strength. Our results indicate that 1 cm capillary at an applied
      voltage of 185 V/cm, filled with commercial gel, was adequate for the separation
      of small DNA fragments in under 1 min. Resolution of large fragments is directly
      proportional to column length at the same field strength. Also, resolution of
      large fragments is higher (better) at lower field strength at constant column
      length. Analysis is fastest (high throughput) using a short capillary and
      moderate field strength (200 v/cm). CE using a single short capillary (2-7 cm) is
      comparable to slab gel in throughput, but more economical. The Sigma DNA buffer
      and hydroxyethyl cellulose liquid gel gave equivalent results in terms of
      resolution and reproducibility. The Sigma DNA replaceable gel gave reproducible
      results when used as received or diluted at 60%. In our hands hydroxyethyl
      cellulose gave more reproducible results than polyacrylamide gel.

PMID- 9237573
TI  - Separation of human plasma/serum proteins by capillary isoelectric focusing in
      the absence of denaturing agents.
AB  - Human plasma/serum proteins were separated by capillary isoelectric focusing in
      the absence of denaturing agents. Proteins focused in a fused silica capillary
      were mobilized by replacing the catholyte sodium hydroxide to acetic acid. The
      performance of the separation of human plasma proteins has been examined by
      changing the duration of the step of isoelectric focusing, carrier ampholyte
      concentration, and plasma protein concentration. The separation patterns of
      plasma proteins were compared with those obtained by micro two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE) run in the absence of denaturants
      in order to locate the major plasma proteins on the capillary electropherograms.
      Using the established electrophoretic conditions and the results of peak
      identification, proteins in the sera of IgG myeloma patients were analyzed by
      capillary isoelectric focusing. The advantages of capillary isoelectric focusing
      in plasma protein analysis compared with 2-D PAGE are discussed.

PMID- 9237574
TI  - Sulfobutylether-beta-cyclodextrin-mediated capillary electrophoresis for
      separation of chlorinated and substituted phenols.
AB  - Cyclodextrin-mediated capillary electrophoresis has been developed for separation
      and analysis of chlorinated as well as substituted phenolic compounds. The
      procedure used a negatively charged sulfobutylether-beta-cyclodextrin (SB-betaCD)
      to effect differential partitioning of the phenols between the buffer and CD
      phases. In 50 mM phosphate buffer containing as low as 1 mM SB-betaCD, 25
      phenolic compounds including 11 Environmental Protection Agency (EPA) priority
      phenols were separated with theoretical plate numbers well above 100,000, for 50
      cm of effective length in most cases. An equilibrium complexation model was used
      for investigating the effect of pH as well as different cyclodextrin
      concentrations on the electrophoretic mobility. The cyclodextrin-mediated
      capillary electrophoresis system was also applicable for separating and
      quantifying the level of pentachlorophenol in contaminated soil samples.

PMID- 9237575
TI  - Capillary electrophoresis of pesticides: V. Analysis of pyrethroid insecticides
      via their hydrolysis products labeled with a fluorescing and UV absorbing tag for
      laser-induced fluorescence and UV detection.
AB  - Some representative standard pyrethroid insecticides, namely permethrin,
      phenotrin, cypermethrin, sanmarton and fenpropathrin, were subjected to base
      hydrolysis with the aim of facilitating the indirect determination of these
      neutral species of low water solubilities by aqueous capillary electrophoresis.
      This first involved the base fragmentation of the pyrethroids in alcohol buffer
      (pH 12.0), and then the selective tagging of the carboxylated hydrolytic products
      with 7-aminonaphthalene-1,3-disulfonic acid (ANDSA) via a condensation reaction
      in the presence of organic soluble carbodiimide. The tagging of the hydrolytic
      products with ANDSA imparted each of the derivatives with two strong sulfonic
      acid groups whose permanent charges were necessary for achieving aqueous
      capillary electrophoresis. In addition, the labeling with ANDSA allowed the
      detection of the derivatives at low levels by capillary electrophoresis laser
      induced fluorescence. The geometric and optical isomers of the ANDSA derivatives
      of the pyrethroid hydrolytic products were best separated when using electrolyte
      systems composed of sodium phosphate buffer, pH 6.5, containing n-octylglucoside
      chiral surfactant in the presence of small amounts of acetonitrile (e.g., 10%
      v/v).

PMID- 9237576
TI  - Isoelectric properties of the soluble matrices in relation to the chemical
      composition of some Scleractinian skeletons.
AB  - Soluble matrices of four Scleractinian skeletons (Madrepora, Favia, Leptastrea
      and Fungia), were extracted and studied by isoelectric focusing (IEF). The main
      part of the extracted matrices is acidic. IEF gels are poorly stained or
      unstained by Coomassie Blue and silver. The positive Alcian Blue staining is
      indicative of a sulfated and acidic nature of the glycoproteins. Chemical
      analysis shows high S contents in Scleractinian skeletons. These results are
      supported by the comparison with IEF and chemical contents of Molluscan shells.

PMID- 9237577
TI  - From genome to proteome: protein map of Haemophilus influenzae.
AB  - High-resolution two-dimensional (2-D) polyacrylamide gel electrophoresis allows
      the separation of complex biological mixtures (i.e., several hundred proteins
      from a bacterial cell lysate) in a single experiment. In this report proteins
      from Haemophilus influenzae were separated by 2-D gels and analyzed by peptide
      mass fingerprinting and/or amino acid analysis. By comparing the peptide mass
      profiles and the amino acid composition with the Haemophilus influenzae database,
      119 protein spots were identified. The combination of amino acid analysis and
      peptide mass fingerprinting is a powerful tool for a rapid and economical
      identification of a large number of proteins resolved by 2-D gels. Studies on
      gene regulation and changes of protein expression upon drug treatment require
      quick and serial analysis techniques to efficiently identify potential new drug
      targets.

PMID- 9237578
TI  - Two-dimensional map of Haemophilus influenzae following protein enrichment by
      heparin chromatography.
AB  - Two-dimensional gel electrophoresis separates several hundred protein molecules
      in one single experiment and is efficiently used to study the products expressed
      by different genomes. Low-copy-number gene products are invisible on a stained
      two-dimensional map and must be enriched such that sufficient amounts are present
      for visualization and identification. We investigated the enrichment of proteins
      of the bacterium Haemophilus influenzae by chromatography on immobilized heparin
      which has affinity for growth and protein biosynthesis factors. Total soluble
      proteins of the microorganism were fractionated on Heparin-Actigel which resulted
      in enrichment of approximately 160 proteins. The eluates, representing about 40%
      of the applied proteins, were analyzed by two-dimensional gel electrophoresis and
      the protein spots were characterized by amino acid composition analysis and
      matrix-assisted laser desorption ionization mass spectrometry. The proteins
      enriched by chromatography on the heparin gel were not exclusively low-copy
      number gene products and they did not exclusively belong to one single class of
      proteins. The proteins that bound to the heparin gel are indicated in a two
      dimensional protein map which includes more than 110 newly identified proteins.

PMID- 9237579
TI  - Thoracoscopic bilateral lung volume reduction for diffuse pulmonary emphysema.
AB  - OBJECTIVE: In a prospective study, we investigated the functional results,
      complications and survival of bilateral video-assisted thoracoscopic (VAT) lung
      volume reduction (LVR) in a selected group of patients with severe, nonbullous
      pulmonary emphysema. From January 1994 to September 1996, 42 of 143 candidates
      (13 female, 29 male, 42-78 years) were operated. They were short of breath on
      minimal exertion due to severe airflow obstruction and hyperinflation (FEV1 <
      30%) pred., TLC > 130% pred., RV > 200% pred.). METHODS: LVR was performed
      bilaterally by VAT using endoscopic staplers without buttressing the staple
      lines. Pulmonary function test (PFT), MRC dyspnea score and 12 min walking
      distance were assessed preoperatively, at 3, 6 and 12 months. In addition lung
      function was measured at hospital discharge. RESULTS: The patients reported a
      marked relief of dyspnea, which persisted at all follow-up visits (P<0.001). FEV1
      increased from 0.80 +/- 0.24 (L) to 1.14 +/- 0.41 (L) postoperatively, a 43% gain
      (P < 0.001). A relevant increase of FEV1 persisted for at least 1 year. The
      residual volume to total lung capacity ratio decreased from 0.64 to 0.56 at
      hospital discharge. The mean 12 min walking distance increased from 500 +/- 195
      (m) to 770 +/- 222 (m) after 1 year (P < 0.001). The mean hospital stay was 13 +/
      5.5 days (median 12.0), drainage time was 9 +/- 4.3 (median 8.0) days. There was
      no 30 day mortality. Three patients died between 2 and 15 months postoperatively
      by non surgery related reasons. One patient underwent lung transplantation 5
      months after surgical lung volume reduction. CONCLUSIONS: In a selected group of
      patients with severe, nonbullous pulmonary emphysema, bilateral LVR by VAT
      results in instantaneous postoperative improvement in pulmonary function and
      dyspnea. These favorable effects, including an amelioriation in exercise
      performance, lasted for at least 1 year.

PMID- 9237580
TI  - Surgical treatment of primary malignant chest wall tumours.
AB  - OBJECTIVE: Primary malignant tumours of the bony chest wall are uncommon and data
      concerning treatment and results are sparse. METHODS: To assess the results of
      surgical resection and chest wall reconstruction we reviewed our experience with
      primary malignant chest wall tumours treated since 1958. RESULTS: Of the 49
      lesions, 42 were found in the ribs and the remaining 7 in the sternum. These
      included chondrosarcomas [22], solitary plasmacytoma [18], Ewing's tumours [7],
      Askin's tumour [1] and Desmoid tumour [1]. Skeletal reconstruction was performed
      in 36 of the 49 patients. Marlex mesh alone was used in 17 patients. Since 1972,
      a sandwich of two layers of Marlex mesh with a filler of methyl methacrylate was
      utilised [19] successfully, producing better functional and cosmetic results.
      Primary soft tissue closure was possible in all but 8 cases in whom latissimus
      dorsi myocutaneous flaps were used. Bilaterally, partially transposed pectoralis
      major muscle was used to cover upper sternal defects in 4 cases. All but 1
      patient had an uneventful post-operative recovery none requiring ventilatory
      support. SURVIVAL: Overall survival at 5 and 10 years was 68%. The differential
      figures for 10-year survival were for chondrosarcoma 67%, Ewing's sarcoma 43%,
      and solitary plasmacytoma 59%. These were the results of radical en-bloc
      excisions. The patient with Desmoid tumour is alive at 5 years, following
      incomplete initial resection and the patient with Askin's tumour survived for 3
      years. CONCLUSION: Radical en-bloc excision remains the treatment of choice in
      all primary malignant chest wall neoplasms except large solitary plasmacytomas
      where incisional biopsy followed by irradiation appears to be the method of
      preference. In Ewing's and Askin's tumours, additional chemotherapy and
      radiotherapy have to be used. The extent of surgical excision should only be
      limited by the amount of tissue necessary to remove for adequate malignant tissue
      clearance, since even large defects can be reconstructed with little functional
      disturbance.

PMID- 9237581
TI  - Surgical relief of tracheobronchial obstruction in infants and children.
AB  - OBJECTIVE: Congenital tracheobronchial obstruction (TBO) presents a complex
      problem both in terms of diverse aetiology, presence of associated anomalies and
      the operative strategy to be adopted. We report a single centre experience in
      managing this difficult problem. METHODS: Twenty-four infants and children with
      TBO referred to our unit over a 12-year period are reviewed. Aetiology of TBO
      included vascular rings (n = 9), anomalous innominate artery (n = 6), congenital
      tracheal stenosis (n = 5), segmental bronchial stenosis (n = 2) and pulmonary
      artery compression of the main bronchi (n = 2). Seven patients had concurrent
      cardiac anomalies. Stridor was the commonest presenting symptom (67%). Mean delay
      from onset of symptoms to referral was 19 months. One patient died preoperatively
      due to acute airway obstruction. Mean age at operation was 33.1 +/- 42 months
      (range 4 days-156 months) and 11 children were under 1 year at the time of
      surgery. In cases of TBO secondary to vascular rings, division of the ring
      resulted in relief of symptoms in seven cases, with two requiring further surgery
      for resultant tracheomalacia. Four of the five patients having tracheal resection
      were operated on with the use of cardiopulmonary bypass; three of these patients
      had concurrent correction of cardiac lesions, with two survivors.
      Tracheobronchial anastomoses were carried out using continuous polydioxanone
      (PDS). Patients with anomalous innominate arteries required aortopexy in five and
      innominate artery suspension in one, while those with pulmonary artery
      compression of the main bronchi had correction of their intracardiac defects (n =
      2). RESULTS: Hospital mortality was 8.7% and there has been one late death due to
      Eisenmenger syndrome secondary to pulmonary regurgitation, atrial septal defect
      (ASD) and patent ductus arteriosus (PDA). On follow-up (mean 40 +/- 31 months),
      19 patients are alive and symptom free. There have been no anastomotic strictures
      following tracheobronchial resection. The single most important predictor of
      mortality was the presence of associated cardiac anomalies. CONCLUSIONS: TBO can
      be managed effectively by a single operation in both infants and children without
      a detrimental effect on tracheal growth. We advocate consideration of concurrent
      repair of the tracheal and cardiac lesions. Cardiopulmonary bypass (CPB) allows
      this concurrent correction of cardiac lesions and also facilitates tracheal
      resection.

PMID- 9237582
TI  - Adenovirus mediated gene transfer into rat lung grafts at the time of harvest.
AB  - OBJECTIVE: New methods to introduce genetic material into cells in vivo may
      revolutionize current treatment modalities. Expression of functional genes in
      lung allografts could be used as a prophylactic strategy for reperfusion injury
      and rejection. We studied the feasibility of ex vivo adenovirus mediated
      transfection of rat lung allografts. METHODS: In group I (n = 3) donor rat lungs
      (Fisher) were flushed with Low Potassium Dextran Glucose (LPDG) solution (20 ml,
      20 degrees C). 4 x 10(11) viral particles of adenovirus 5 containing the E. coli
      lacZ reporter gene coding for beta-galactosidase (AdCMV-beta-Gal) were added to
      the last milliliter of the flush solution. Lung grafts were stored for 3.5 h at
      room temperature followed by syngenic orthotopic transplantation (Fisher to
      Fisher) using a microsurgical cuff technique. On postoperative day 5 the heart
      lung block was extracted and flushed with x-Gal (beta-Gal substrate) and kept in
      x-Gal for 3 h at 37 degrees C. Color development was observed macroscopically and
      plastic embedded sections were used for histologic examination. Group II grafts
      (n = 3) served as controls and were flushed without adenovirus. RESULTS: X-Gal
      stained the transfected lung grafts blue, indicating high reporter gene
      expression. Control lungs did not stain with x-Gal. In group I histological
      examination demonstrated transfection predominantly in type II pneumocytes.
      Surprisingly endothelial cells showed no beta-Gal activity. CONCLUSION: This
      study demonstrates that ex vivo transfection of lung grafts at the time of
      harvest is a feasible method of gene transfer and results in gene expression
      after transplantation.

PMID- 9237583
TI  - Medium term results of direct bronchial arterial revascularisation using IMA for
      single lung transplantation (SLT with direct revascularisation).
AB  - OBJECTIVE: To describe a technique of direct revascularisation of the bronchial
      artery using the left IMA and assess its medium term results in patients
      undergoing left single lung transplant (SLT). METHODS: Between March 1991 and
      September 1993, 22 patients who underwent direct bronchial revascularisation at
      the time of left SLT (20 pedicled IMA, one free IMA, and one direct anastomosis
      to the aorta) have been followed up for a minimum period of 1 year (mean 30 +/-
      12 months). Their mean age was 47.8 +/- 9.6 and the original disease was
      emphysema in 19, lymphangioleiomyomatosis in two, and pulmonary fibrosis in one.
      The mean ischaemia time was 269.7 +/- 23.4 min. RESULTS: There was one early
      death (4.5%) and 3 patients were re-explored for bleeding. The actuarial survival
      at 1 and 3 years was 91 +/- 0.4% and 82.6 +/- 1%, respectively. Bronchial healing
      was excellent in all patients and angiographic studies showed patent vascular
      anastomosis in all 22 patients, with good run off in 20 and poor in two. One
      patient developed clinical obliterative bronchiolitis at 22 months (4.5%) during
      a period of follow up varying from 12 to 43 months (mean 30 S.D. 12). At last
      follow up the mean FEV1 was 1.4 +/- 0.4 and the mean FVC was 2.2 +/- 0.6. On
      average, each patient developed 1.5 +/- 0.6 infection episodes and 1 +/- 0.2
      acute lung rejection. CONCLUSION: It is concluded that the medium term results of
      direct bronchial revascularisation are good. However the influence of this
      procedure on long term results needs further investigation.

PMID- 9237584
TI  - Resting hemodynamics after total versus standard orthotopic heart transplantation
      in patients with high preoperative pulmonary vascular resistance.
AB  - OBJECTIVE: Pretransplant pulmonary vascular resistance > or = 4 Wood-units
      predisposes to right ventricular failure after heart transplantation. Total
      orthotopic heart transplantation with bicaval and pulmonary venous anastomoses
      offers synchronous contractions of the atria and a normal ventricular filling
      pattern, but requires longer ischemic time than standard orthotopic heart
      transplantation. To test if total orthotopic heart transplantation improves
      resting hemodynamics in pts with high preoperative pulmonary vascular resistance,
      we analyzed 65 pts with standard and 65 with total orthotopic heart
      transplantation transplanted between 12/88 and 7/94. Of these, 18 with total and
      15 with standard orthotopic heart transplantation had a preoperative pulmonary
      vascular resistance > or = 4 Wood-units. METHODS: Right heart catheterization
      data were obtained at each endomyocardial biopsy. All data from biopsies at both
      2 weeks and 1 year posttransplant that were free from humoral or greater than 1A
      cellular rejection (9 versus 13 pts) were included in a two way ANOVA. Pts with
      postop pacemakers, atrial fib or beta-blocker therapy at the time of biopsy were
      excluded. RESULTS: Ischemic time was different (172 +/- 44 versus 142 +/- 28 min,
      P = 0.03). Demographics, NYHA class, pre-TX hemodynamics, donor age and inotropes
      were similar. Cardiac output and index were higher in the total orthotopic group
      at 2 weeks (6.5 +/- 1.7 versus 5.1 +/- 1.0 l/min; 3.4 +/- 0.9 versus 2.8 +/- 0.6
      l/min per m2) and 1 year (7.1 +/- 2.0 versus 4.9 +/- 1.1 l/min, P = 0.002; 3.6 +/
      1.1 versus 2.6 +/- 0.5 l/min per m2, P = 0.009). Right atrial and pulmonary
      arterial mean pressure (mmHg) were lower with total orthotopic heart
      transplantation at 2 weeks (6 +/- 4 versus 9 +/- 5, P = 0.04; 22 +/- 3 versus 25
      +/- 7, P = 0.1) and 1 year (5 +/- 2 versus 7 +/- 3, P = 0.02; 19 +/- 4 versus 25
      +/- 7, P = 0.03). Pulmonary capillary wedge pressure (mmHg) was borderline
      nonsignificant (11 +/- 4 versus 13 +/- 7 at 2 weeks, 8 +/- 3 versus 14 +/- 5 at 1
      year, P = 0.055), as well as pulmonary vascular resistance (1.9 +/- 1 versus 2.5
      +/- 1 at 2 weeks, 1.5 +/- 0.6 versus 2.7 +/- 1.7 WU at 1 year, P = 0.051).
      CONCLUSIONS: Total orthotopic heart transplantation improves cardiac output and
      index in pts with high preoperative pulmonary vacular resistance. There is a
      lower mean RA and PA pressure perhaps due to less tricuspid and mitral
      regurgitation. In view of the frequently observed restrictive filling pattern
      after cardiac transplantation, total orthotopic heart transplantation can be
      beneficial until this pattern has subsided by preserving atrioventricular
      synchrony and offering better atrial transport.

PMID- 9237585
TI  - Improvement of heart-, lung-, and liver-performance during mechanical circulatory
      support by the Novacor-system.
AB  - OBJECTIVE: Since its clinical introduction, the Novacor left ventricular assist
      system (LVAS) has proved to be a reliable and safe method for bridging to cardiac
      transplantation. To find out whether univentricular assistance is sufficient in
      patients with severe global heart failure, multi organ monitoring using the COLD
      system was performed. METHODS: In seven patients (mean age 38.8 years), the
      wearable Novacor system N100 was implanted. Preoperatively, during the first 72 h
      thereafter and before heart transplantation right and left ventricular cardiac
      output, right ventricular ejection fraction, pulmonary-, intrathoracic-and total
      blood volume, extravascular lung water and excretory liver function were
      monitored by means of double indicator dilution technique with the COLD system.
      Conventional hemodynamic parameters have also been documented. RESULTS: During
      left ventricular assistance, both pulmonary and systemic arterial cardiac outputs
      increased significantly (Student's t-test, P < 0.05). Right ventricular ejection
      fraction rose from 17 to 26%, preoperatively elevated pulmonary and intrathoracic
      blood volumes and extravascular lung water fell significantly to normal ranges.
      Total blood volume remained constant, excretory liver function improved markedly.
      CONCLUSIONS: Pulmonary cardiac output improves due to the reduced right
      ventricular afterload by unloading the impaired left ventricle with the Novacor
      pump. The drop in pulmonary blood volume, intrathoracic blood volume and
      extravascular lung water also indicates a decrease of pulmonary congestion. Since
      total blood volume remains unchanged, a volume shift to the systemic circulation
      is suggested, resulting in an improved splanchnic perfusion as demonstrated by a
      better excretory liver function. In the absence of primary pulmonary
      hypertension, treatment of global heart failure with a left ventricular assist
      device is possible. The COLD system is a useful tool for managing this patient
      group during the postoperative period.

PMID- 9237586
TI  - Video-thoracoscopic surgical interruption of patent ductus arteriosus. Routine
      experience in 332 pediatric cases.
AB  - OBJECTIVE: Pediatric video-assisted thoracic surgery closure of patent ductus
      arteriosus can now be performed on a routine basis. We review here our entire
      experience with this technique. METHODS: Three hundred and thirty two consecutive
      patients underwent video-assisted closure of patent ductus arteriosus from
      September 1991 to September 1996. Indications were symptomatic ductus or failure
      of closure in older children. All complications were carefully noted, as well as
      intensive care unit stay, and operating room time. RESULTS: Patients were divided
      in three age groups: less than 6 months (101 patients, 31%), 6-48 months (179
      patients, 54%), greater than 48 months (52 patients, 16%). The mean weight was
      12.6 kg (range 1.2-65 kg). Associated cardiac anomalies were atrial septal defect
      (3), ventricular septal defect (5), anomalous pulmonary venous return (1). Six
      patients had a residual shunt following video-assisted interruption. Five
      patients had successful immediate clip repositioning (three via video-assisted
      interruption, two via thoracotomy). One patient continued to have a small shunt,
      which is followed medically. Complications included recurrent laryngeal nerve
      dysfunction in six patients (1.8%) (five transient, one persistent). Mean
      operating time was 20 +/- 1.5 mn and hospital stay averaged 48 h (> 6 months), 72
      h (< 6 months). CONCLUSIONS: Interruption of patent ductus can be safely
      performed by video-assisted technique with minimal morbidity and no mortality. It
      can be performed in all age group with minimal hospital stay.

PMID- 9237587
TI  - Surgical treatment of a fistula between the right pulmonary artery and the left
      atrium: presentation of two cases and review of literature.
AB  - OBJECTIVE: A direct communication between the pulmonary artery and the left
      atrium is a rare anomaly. On the basis of two cases of our own and a literature
      review of 49 cases, we focus on clinical presentation, anatomy, diagnosis, and
      the role of surgery. METHODS: Two cases of a fistula between the right pulmonary
      artery and the left atrium are described in a girl of 4 years and a boy of 15
      years. Both presented with unexplained cyanosis. Diagnosis was made on
      echocardiography and angiography. The fistula was ligated using extracorporeal
      circulation in the first case and not in the second case. RESULTS: The surgical
      results were successful with resolution of the cyanosis. CONCLUSIONS: In
      newborns, urgent surgery may be necessary. In other patients, early elective
      surgical correction should be performed to prevent complications, especially
      systemic and cerebral emboli, cerebral abscesses, and rupture of aneurysmal
      fistulas. Complete cure can be achieved by ligation and possible division or by
      intracardiac repair.

PMID- 9237588
TI  - Pre- and postoperative exercise capacity associated with hemodynamics in adult
      patients with atrial septal defect: a retrospective study.
AB  - OBJECTIVE: This study evaluated the pre- and postoperative exercise capacity in
      adult patients with atrial septal defect (ASD) associated with hemodynamic
      variables. METHODS: Adults (70) with ASD underwent symptom-limited exercise
      tests. Peak O2 uptake (Peak VO2) and % peak VO2, that is the percentage of
      predicted value, were measured. These patients were divided into three groups
      according to pulmonary-to-systemic flow ratio (Qp/Qs) and systolic pulmonary
      arterial pressure (PAs); Group A: Qp/Qs < or = 3, PAs < or = 50 mm Hg, Group B:
      Qp/Qs > 3, any PAs, Group C: Qp/Qs < or = 3, PAs > 50 mm Hg. Exercise test was
      repeated in 22 patients after surgical closure of ASD (mean 4.6 +/- 2.0 months).
      RESULTS: Peak VO2 was significantly lower in group B (P < 0.01) and group C (P <
      0.01) than in group A (19.3 +/- 5.7, 17.6 +/- 3.6, 27.6 +/- 6.3 ml/min/kg,
      respectively). In patients except those in group C, there were a weak negative
      correlation between PAs and % peak VO2 (r = 0.61) and a significant negative
      correlation between Qp/Qs and % peak VO2 (r = 0.86). Postoperative peak VO2
      increased significantly in group A (27.2 +/- 5.1-31.1 +/- 5.1 ml/min/kg, P <
      0.05) and group B (16.7 +/- 3.3-21.5 +/- 2.1 ml/min/kg, P < 0.01). However, there
      was no significant difference between pre- and postoperative peak VO2 in group C
      (16.8 +/- 1.3-17.8 +/- 2.8 ml/min/kg, NS). CONCLUSIONS: In ASD patients except
      those with small or moderate left-to-right shunt and high pulmonary arterial
      pressure, there was a significant negative correlation between Qp/Qs and peak VO2
      corrected by age and gender. Patients with large left-to-right shunt and/or high
      pulmonary arterial pressure had reduced exercise capacity. However, exercise
      capacity in patients with large left-to-right shunt increased after closure of
      ASD regardless of whether they had high pulmonary arterial pressure.

PMID- 9237589
TI  - Mitral valve replacement via a right mini-thoracotomy in the dog: use of carbon
      dioxide to reduce intracardiac air.
AB  - OBJECTIVE: To develop a clinically applicable method of minimally invasive mitral
      valve replacement (MVR) with cardioplegia, and examine the ability of carbon
      dioxide (CO2) to improve de-airing. METHODS: MVR was performed via a 5 x 3-cm
      right lateral minithoracotomy in eight greyhounds. Peripheral cardiopulmonary
      bypass and an ascending aortic balloon catheter (endoaortic clamp) were used for
      cardioplegia and aortic root venting. The endoaortic clamp was inflated in the
      ascending aorta under fluoroscopy and cardioplegic solution was infused. In four
      dogs, CO2 at 2 l/min was used to displace air in the chest. A left atriotomy was
      made, the valve exposed and a mechanical valve implanted. After left atrial
      closure, retained intracardiac gas was aspirated from the aortic root and
      collected in a bubble-trap. The endoclamp was deflated and the animal weaned from
      bypass. RESULTS: A satisfactory MVR was performed in all cases. The clamp time
      was 64 +/- 13 min and all dogs were stable post-bypass. In the CO2 group,
      intrathoracic CO2 was maintained above 86% and 0.1 +/- 0.1 ml of gas was
      collected, compared to 1.3 +/- 0.8 ml in the non-CO2 group (P < 0.05).
      CONCLUSIONS: Femoro-femoral bypass and use of the endoaortic clamp allow a safe
      and efficacious MVR via a right minithoracotomy in the dog. A high intrathoracic
      CO2 concentration reduces the amount of retained intracardiac gas.

PMID- 9237590
TI  - Cardiac events after combined surgery for coronary and carotid artery disease.
AB  - OBJECTIVE: To evaluate serious cardiac events after combined (either single or
      two stage) coronary artery surgery (CAS) and carotid endarterectomy (CEA) for
      concomitant coronary and carotid artery disease. METHODS: We have analyzed our 15
      year experience (January 1981-September 1996) with 201 consecutive patients
      operated on using both approaches. Group A consisted of 48 patients with the
      single-stage procedure, while in group B (153 patients), two stage procedure was
      carried out, either as carotid endarterectomy (CEA), followed by coronary artery
      bypass surgery (CAS) (group B1- 103 patients), or as CAS followed by CEA (group
      B2- 50 patients). Five patients from B1 group died after the CEA procedure, but
      were included, despite the fact they never reached the second stage. Left main
      coronary artery disease was found in 41 patients (20.4%), poor left ventricular
      function in 49 (24.4%) previous MI in 133 (66.2%), while 136 (67.7%) were in NYHA
      functional class III or IV. Bilateral carotid involvement was present in 61
      patients (30.3%). Unstable angina was more prevalent in groups A and B2 (P <
      0.0001). NYHA class III/IV in group A (versus B1, P = 0.001 and versus B2, P =
      0.02), low ejection fraction in groups A and B2 (P < 0.0001), bilateral carotid
      stenosis in group B1 (versus A, P = 0.003 and versus B2, P < 0.0001), and
      ulcerated plaque in group B1 (P < 0.0001). These differences dictated the
      surgical strategy, which resulted in different protocols for clinical and
      operative management. RESULTS: Early mortality for the entire group was 5.5%
      (11/201) 6.2% in group A, 7.8% in group B1 and 0% in group B2, respectively; (P >
      0.05). Serious morbidity occurred in 7.5% of patients (8.3% in group A, 7.8% in
      group B1 and 6% in group B2, respectively; P > 0.05). Univariate analysis
      revealed only bilateral carotid stenosis to influence early outcome (P = 0.04).
      CONCLUSION: Patients with concomitant coronary and carotid artery disease have
      relatively good immediate operative results, providing all existing lesions are
      corrected. Despite it did not reach the statistical significance, cardiac events
      were less frequent in groups A and B2 indicating possible protective effect of
      prior CAS in patients with concomitant disease.

PMID- 9237591
TI  - Early results with the minimally invasive thoracotomy for myocardial
      revascularization.
AB  - OBJECTIVE: We report the early results of the left anterior descending artery
      revascularization through a minimally invasive thoracotomy, examining the main
      technical aspects of the operation. METHODS: From January 1995 to September 1996,
      51 patients underwent myocardial revascularization through a mini-thoracotomy on
      beating heart without cardiopulmonary bypass. The main indication to operation
      was limited lesions of the left anterior descending artery with contra
      indications or high risk of failure of angioplasty. The position of the patient
      was the same than traditional surgery; the chest was opened on the fourth left
      intercostal space; the left internal mammary artery harvested under direct
      vision; temporary occlusion of the left anterior descending was obtained
      prevalently using 5-0 poliypropilene sutures; the anastomosis was performed with
      single or double 7-0 or 8-0 suture. In six patients the chest was closed and a
      conventional open-heart operation was performed due to internal mammary artery or
      left anterior descending unsuitability for minimally invasive revascularization.
      All the patients were submitted after operation to early angiographic control
      and/or a Doppler study of the mammary flow. RESULTS: There was no intra-operative
      mortality. One patient had a postoperative myocardial infarction of the anterior
      lateral wall of the left ventricle, and died after an emergency open-heart
      operation. In one case the patient was reopened after a few hours for a bleeding.
      Three patients showed various degrees of anastomotic stenosis at the angiographic
      control. CONCLUSIONS: Several technical difficulties can play an important role
      in the operative outcome because a single repeated technical error could not
      fully explain these heterogeneous observed failures. The technique of myocardial
      revascularization through a left anterior small thoracotomy might present several
      critical points, particularly: (1) the harvesting of LIMA, meaning the
      preservation of integrity of the arterial wall and adequacy of the length; (2)
      the method of the temporary closure of the LAD during of the anastomosis; (3) the
      stabilization of the LAD and the surgical technique of the anastomosis; (4) the
      methods for intraoperative control of the patency of the anastomosis. All points
      mentioned have been thought in our experience to be causes of early failure.

PMID- 9237592
TI  - ITA versus SVG: a comparison of instantaneous pressure and flow dynamics during
      competitive flow.
AB  - OBJECTIVE: Competitive flow from patent native coronary vessels is implicated in
      the failure of internal thoracic artery (ITA) grafts, but it is not thought to
      affect saphenous vein graft (SVG) patency. This study examines instantaneous
      pressure and flow dynamics in left ITA and SVG grafts in competition with a
      patent left anterior descending (LAD) artery. METHODS: SVG (3.0-4.0 mm) and ITA
      (1.5-2.0 mm) to proximal LAD (2.5-3.0 mm) coronary bypass was performed in 10
      mongrel dogs. Flow and pressure were measured in the occluded (No Competition)
      and opened (Competition) ITA, SVG and LAD. RESULTS: The ITA and SVG, when each
      was the sole inflow to the LAD, provided similar flow as the native LAD. During
      competitive flow, total LAD flow was preserved and flow in the ITA and SVG were
      reduced (8.20 +/- 1.25 and 10.00 +/- 1.73 ml/min; P < 0.005). SVG diastolic flow
      was reduced to 11.52 +/- 2.17 ml min (55.5%); P < 0.003. Flow in the SVG remained
      predominantly antegrade. In contrast, ITA diastolic flow was reduced more
      drastically, to 5.37 +/- 1.25 ml/min (80.7%); P < 0.0001. When the ITA was the
      only inflow to the LAD, there was delay in the LAD pressure wave. This delay
      disappears during competition due to the large, systolic retrograde flow up the
      ITA. CONCLUSION: The ITA, compared to the SVG, is a longer and narrower conduit
      with lower levels of flow during competition. Due to a delay in the pressure
      wave, the ITA flow is retrograde during early systole. Low levels of flow, with a
      markedly decreased diastolic phase, and the oscillating pattern in systole
      (retrograde/antegrade) may be poorly tolerated by the ITA endothelium and lead to
      graft deterioration.

PMID- 9237593
TI  - Fiberoptic-guided CO2 laser for harvesting of the internal mammary artery.
AB  - OBJECTIVE: The internal mammary artery is the preferred conduit in coronary
      artery bypass grafting. Although most centers use electrocautery to dissect the
      internal mammary artery, it has several disadvantages. The purpose of this study
      in a canine model was to evaluate and compare a fiberoptic CO2 laser device
      versus electrocautery for harvesting the internal mammary artery. MATERIAL AND
      METHODS: In ten mongrel dogs, both internal mammary arteries with their
      surrounding pedicles, were dissected from the thoracic wall, using a low-current
      electrocautery for one artery and a continuous wave, fiberoptic-guided CO2 laser
      (13 watts) for the contralateral vessel. Blood flow through the vessels was
      measured immediately after dissection. RESULTS: Mean flow through the laser
      dissected arteries was 71.3 +/- 23.7 ml/min versus 52.9 +/- 16.5 ml/min in those
      dissected using electrocautery. Histological examination of the chest wall
      specimens dissected with electrocautery showed the presence of necrosis, edema
      and hemorrhage surrounding the muscle, while the specimens dissected with the
      laser revealed only a narrow area of burn on the surgical margins of the muscle.
      The laser-assisted dissection was more accurate, as easy, and almost as fast as
      with the use of electrocautery. CONCLUSIONS: Stripping of the internal mammary
      artery with the fiberoptic CO2 laser offers a promising alternative to
      electrocautery. Owing to its greater accuracy, the laser technique may reduce the
      likelihood of damaging the endothelial lining of the dissected vessel. By
      reducing the degree of soft tissue damage, the CO2 laser may also lower the
      incidence of sternal wound infection and reduce postoperative chest wall pain and
      dysesthesia.

PMID- 9237594
TI  - Evaluation of preoperative intra-aortic balloon pump support in high risk
      coronary patients.
AB  - OBJECTIVE: The intra-aortic balloon pump (IABP) is an established additional
      support to pharmacological treatment of the failing heart after myocardial
      infarction, unstable angina and cardiac surgery. The effect of preoperative IABP
      in high risk patients was evaluated. METHODS: Between June 1994 and March 1996
      all high risk patients for CABG (two or more of these criteria: Left ventricular
      ejection fraction (LVEF) < or = 40%, left main stem stenosis > or = 70%, REDO
      CABG, unstable angina) were randomized into either of 3 groups: (1) IABP 1 day
      prior to surgery, (2) IABP 1-2 h prior to CPB and (3) no preoperative IABP,
      controls. EXCLUSION CRITERIA: cardiogenic shock preoperatively. Fifty-two
      patients have entered the study-group 1 (13 patients), group 2 (19 patients) and
      group 3 (20 patients). Preoperative patient characteristics and operative data
      revealed no group differences. There were 56% REDO's, unstable angina 59%, LVEF <
      or = 40%, 87% (34.0 +/- 11.6%) and left main stem stenosis in 35%. RESULTS: The
      CPB-time was shorter in groups 1 and 2 88.7 +/- 20.3 min than in group 3 105.5 +/
      26.8 min, P < 0.001, while ischemia time did not differ. Hospital mortality was
      higher in group 3, 25% vs. 6% (groups 1 and 2). Postoperative low cardiac output
      was seen in 12 patients (60%) in group 3 vs. 6 patients (19%) in groups 1 and 2,
      P < 0.05. Cardiac index increased significantly prior to CPB in groups 1 and 2.
      After CPB cardiac index was significantly higher in groups 1 and 2 compared to
      Group 3 and continued to increase. The IABP was removed after 3.1 +/- 1.0 days in
      group 3 vs. 1.3 +/- 0.6 days in groups 1 and 2, P < 0.001. In group 3, 11
      patients required IABP postoperatively compared to only 4 patients in groups 1
      and 2. ICU stay was shorter in groups 1 and 2--2.3 +/- 0.9 days vs. 3.5 +/- 1.1
      days for group 3, P = 0.004. All patients received dopamin postoperatively,
      however in a lower dose in groups 1 and 2, 4.5 vs. 13.5 microg/kg/min. Dobutamine
      was added in 23% of the patients (group 1), 32% (group 2) and 95% (group 3).
      Adrenalin/amrinonum was required in 40% of the patients in group 3, 5% in group 2
      and none in group 1. Group 1 patients had a better improvement of cardiac
      performance than group 2, while other parameters did not differ. Three months
      follow up of hospital survivors showed no group differences. CONCLUSIONS: The use
      of preoperative IABP in high risk patients lowers hospital mortality and shortens
      the stay in ICU, due to improved cardiac performance, compared to a controls. The
      procedure was cost-beneficial. One day preoperative IABP treatment improves
      cardiac performance more than 1-2 h preoperative IABP treatment, but does not
      significantly affect the outcome in terms of hospital mortality or postoperative
      morbidity.

PMID- 9237595
TI  - Hibernating myocardium: clinical and functional response to revascularisation.
AB  - OBJECTIVE: We assessed the effects of coronary bypass grafting on left
      ventricular (LV) function, exercise capacity and symptom profile in patients with
      LV impairment and evaluated the role of identifying myocardial hibernation in a
      prospective non-randomised study. METHODS: Of 120 patients screened, 47 patients
      with LV ejection fraction < 35% and three vessel coronary artery disease were
      studied. All underwent stress/redistribution and separate day rest/redistribution
      T1-201 imaging together with cine MRI at enrolment, and cine MRI at follow-up.
      Group 1, 30 patients undergoing bypass surgery, underwent symptom limited
      treadmill exercise testing with peak VO2 measurement, and symptom profile
      evaluation less than 3 months before, and 3-6 months after operation.
      Revascularisation was assessed by post-operative T1-201 imaging and repeat
      coronary angiography. Group 2, 17 patients treated on medical therapy alone
      underwent symptom profile assessment at enrolment and follow-up for those who
      survived. Segmental hibernation was defined as the equivalent of greater than 50%
      of maximal T1-201 uptake where wall motion was severely impaired on resting
      imaging. Patients were considered to be hibernating where two of nine LV segments
      fulfilled these criteria. RESULTS: In group 1, five patients died (17%), peri-or
      post-operatively, two defaulted and 23 attended follow-up studies. In group 2,
      three patients died prior to follow-up (18%). In the surgical group there was an
      increase in mean LVEF from 24.0 +/- 8% to 29.7 +/- 11% (P < 0.05) while in the
      medical group there was a fall from 25.7 +/- 10% to 20.6 +/- 8% (P < 0.05). In
      group 1, the mean NYHA dyspnoea grade improved from 2.7 to 1.4 while in the
      medical group it was unchanged, 2.6 to 2.5. In patients with myocardial
      hibernation identified pre-operatively, 18/19 (95%) improved LVEF after CABG
      compared with 2/4 (50%) of patients without hibernation. 17/19 (86%) patients
      with hibernation improved NYHA dyspnoea class compared with 2/4 (50%) of patients
      without. 60/93 (65%) of hibernating segments improved function after
      revascularisation while 47/53 (89%) hibernating segments showed no improvement on
      medical therapy alone. CONCLUSION: In patients with severe LV impairment with
      myocardial hibernation, coronary artery bypass grafting improves both global and
      regional systolic LV function, and symptom profile. Medical treatment of patients
      with LV impairment and myocardial hibernation does not improve LV contractile
      function or symptoms. Both surgical and medical therapy carry a high mortality
      rate.

PMID- 9237596
TI  - Preconditioning during warm blood cardioplegia.
AB  - OBJECTIVE: Preconditioning describes the cardioprotective effects of multiple
      brief episodes of warm ischemia. The purpose of the study was to determine
      whether warm ischemia, during the intermittent delivery of warm blood
      cardioplegia, would induce preconditioning during cardioplegia arrest. METHODS:
      Dogs, 15, were randomized to a preconditioning protocol or to serve as controls.
      The control group received 60 min of continuous warm blood cardioplegia (WBC)
      followed by 30 min of warm arrested ischemia. The preconditioned group were
      arrested with WBC and then underwent three consecutive cycles consisting of 10
      min of warm ischemia followed by 10 min of reperfusion. Reperfusion was provided
      by a continuous infusion of WBC. The preconditioning protocol was followed by 30
      min of warm arrested ischemia. Myocardial functional recovery was assessed before
      cardiopulmonary bypass and cardioplegia arrest and again 30, 60 and 90 min after
      the arrest. Pressure-volume loops were used to measure the maximum elastance of
      the left ventricle (Emax), diastolic compliance, and used to calculate preload
      recruitable stroke work area. RESULTS: Myocardial functional recovery was better
      preserved after 30 min of warm arrested ischemia in those animals that had been
      preconditioned. CONCLUSION: Preconditioning may be induced when warm blood
      cardioplegia is delivered intermittently during cardioplegia arrest.

PMID- 9237597
TI  - Warm blood cardioplegia in high risk patients.
AB  - OBJECTIVE: Despite overall good clinical results, cardiac surgery in high risk
      patients, such as those with poor left ventricular function or heavily
      hypertrophied myocardium, is still challenging. This study was designed to assess
      the efficacy of warm blood cardioplegia (WBC) in these two subgroups of patients.
      METHODS: Fifty-two patients, with an ejection fraction less than 50%, who
      underwent surgical revascularization, and 36 patients, with marked left
      ventricular hypertrophy (LVH), who were operated on for aortic valve replacement
      (AVR), were consecutively studied. All of them received continuous retrograde
      'warm' blood cardioplegia. Results were assessed on clinical outcomes and
      compared with those predicted from a risk-stratifying index which has been
      previously validated in a large multicenter population-based study (Ontario
      score). RESULTS: For cardiac revascularization, the rates of overall hospital
      mortality, Q-wave infarctions and inotropic use were respectively 5.8%, 9.6% and
      21.1%, comparing favorably with those of the Ontario Group. For aortic valve
      replacement, the incidence of hospital mortality and Q-wave infarction was 2.8%.
      CONCLUSIONS: By virtue of the study design, these data cannot conclusively
      establish the superiority of warm blood cardioplegia over other methods of
      myocardial protection. However, they support the safety of this technique, and
      suggest that these subgroups of high risk patients might represent the elective
      indication for aerobic arrest.

PMID- 9237598
TI  - Effect of milrinone and atrial pacing on stunned myocardium.
AB  - OBJECTIVE: Most mammalian cardiac muscles show a positive force-frequency
      relation, which is turned into a negative relation in failing hearts. Stunned
      myocardium shows similar defects as failing myocardium, it has a functional
      reserve recruitable by positive inotropic interventions, and possibly shows a
      disturbed response to increased heart rate. The present experiments compare in
      vivo the response of stunned and intact myocardium to atrial pacing before and
      during inotropic stimulation by milrinone. METHODS: In anaesthetised
      (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure,
      left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow,
      myocardial systolic shortening in the LAD and LCX area were monitored, and
      myocardial power was calculated. The LAD region was subjected to ischaemia and
      reperfused. Heart rate was raised by right atrial pacing after 90 min reperfusion
      before and during i.v. milrinone (105 microg/kg bolus + 8 microg/kg per min
      infusion). The ischaemic/reperfused area was sliced post mortem and stained by
      triphenyl tetrazolium chloride to exclude myocardial infarction. Data from ten
      experiments are presented. RESULTS: After 90 min LAD reperfusion, LAD blood flow
      and power were 110 and 36% of preischaemic control, respectively, indicating
      myocardial stunning. The power of the intact area was not changed (102% of
      control). Pacing from 87 to 164 per min increased the power of the intact area
      (+96%), the power of the stunned myocardium decreased (-64%). Milrinone increased
      the power of the stunned region to 72% of the pre-stunning level and the power of
      the intact area by +51%. Pacing from 111 to 164 per min during milrinone
      increased the power of the intact myocardium to the same level as before
      milrinone, the power of the stunned region did not change. CONCLUSIONS: Stunned
      myocardium responds pathologically to atrial pacing with a negative staircase in
      contrast to the positive staircase of intact myocardium. Inotropic stimulation by
      the phosphodiesterase inhibitor milrinone recruited the functional reserve of
      stunned myocardium. Milrinone did not restore a positive staircase in stunned
      myocardium, but power was maintained during atrial pacing. The pathological
      staircase of stunned myocardium may arise from an impaired availability of cyclic
      AMP, but the data do not exclude defects in calcium handling, a dysfunction of
      the sarcoplasmic reticulum, or an impaired Ca-sensitivity of the myofilaments.

PMID- 9237599
TI  - Perioperative risk factors affecting hospital stay and hospital costs in open
      heart surgery for patients > or = 65 years old.
AB  - OBJECTIVE: Demographic changes, associated with increased demands for open heart
      surgery in the elderly, place increased burden on financial resources. To
      evaluate perioperative risk factors affecting incidence of hospital events and
      estimation of hospital charges, 2577 patients > or = 65 years (range 65-91),
      operated on from January 1991 to December 1994, were compared with a concurrent
      cohort of 2642 younger patients. METHODS: Statistical analysis, by surgical
      procedure, focused on hospital mortality, key postoperative complications
      affecting length of hospital stay and hospital charges. RESULTS: Overall hospital
      mortality was 4.7%, 3.5% in younger patients versus 6.1% in the older group (P <<
      0.01). Mortality was significantly lower in patients less than 65 years
      undergoing coronary artery bypass grafting (3% versus 5%, P < 0.01) and valve
      replacement (4% versus 9%, P = 0.01). Significant risk factors for hospital death
      in the elderly: diabetes (P < 0.01), hypertension (P < 0.01), myocardial
      infarction (P < 0.01) and congestive heart failure (P < 0.01). Significant
      postoperative events, more common in older patients, included prolonged
      ventilation (P << 0.01), congestive heart failure (P << 0.01), infection (P <<
      0.01), cerebrovascular accident (P < 0.01), and intra aortic balloon pump (P <
      0.01). Incremental risk factors for morbidity in the elderly were: higher New
      York Heart Association class, congestive heart failure, emergent operation, and
      female gender. Mean length of hospital stay for the < 65 group was 15.3 versus >
      19.5 days for the > 65 group (P << 0.01). Length of stay over 18 days positively
      correlated with increased morbidity in both age groups. For patients > or = 65
      years of age, the average hospital charge for open heart surgery was 172% higher
      for patients with a length of stay greater than 18 days compared with 165% for
      patients less than 65 years of age. CONCLUSIONS: Higher operative mortality and
      longer length of stay in elderly patients, resulting in increased health care
      costs, was associated with more co-morbidities. These results suggest
      interventions designed to reduce congestive heart failure and other co
      morbidities may improve patient's recovery and reduce costs.

PMID- 9237600
TI  - Cardio-pulmonary-bypass time has important independent influence on mortality and
      morbidity.
AB  - OBJECTIVE: To determine the influence of cardio-pulmonary-bypass-time on hospital
      mortality and ICU-morbidity in isolated CABG surgery. METHODS: Between 1985 and
      1994 perioperative data of 8578 consecutive CABG operations were prospectively
      collected. Seven variables: gender, redo vs. primary operation, elective vs.
      urgent surgery, age in 4 categories, use of IMA, number of distal anastomoses (>
      4 vs. < = 4), and cardio-pulmonary-bypass-time in four categories were entered in
      multivariate logistic regression analysis and odds ratios for respective cardio
      pulmonary-bypass-time-categories with regard to mortality, length-of-stay in the
      ICU and 8 ICU-complications were calculated. Bypass-time up to 90 min was the
      reference category, the other categories were from 1.5 to 2.5 h, 2.5 to 3.5 h,
      and longer than 3.5 h. RESULTS: 8337 operations had complete data. Mortality and
      ICU-morbidity were low. The odds ratios for mortality were 2.3 (P = 0.0094), 7.4
      (P < 0.0001) and 20.7 (P < 0.0001) for ascending bypass-time-categories. The odds
      ratios for prolonged ICU-stay were 1.8 (P = 0.0002), 3.3 (P < 0.0001) and 7.9 (P
      < 0.0001) for ascending bypass-time-categories. For postoperative complications
      the same pattern was found: consequently higher odds ratios for longer bypass
      time-categories. CONCLUSION: The highly significant correlation between cardio
      pulmonary-bypass-time-category and the occurrence of undesirable postoperative
      events is demonstrated by the consequent rise in odds ratios. This independent
      influence of cardio-pulmonary-bypass-time on outcome reflects both problems
      encountered during revascularisation and time-related influence of cardio
      pulmonary-bypass on the human body. When a predictive model was created, CPBT
      proved to be a good predictor of undesirable postoperative events.

PMID- 9237601
TI  - Sternal wound complications--incidence, microbiology and risk factors.
AB  - OBJECTIVE: Sternal wound complications, i.e. instability and/or infection
      (mediastinitis), are important causes of morbidity in patients undergoing cardiac
      surgery via median sternotomy. Coagulase negative staphylococci, a normal
      inhabitant of the skin, have evolved as a cause of sternal wound infections.
      Since these opportunistic pathogens often are multiresistant, they can cause
      therapeutic problems. METHODS: From 1980 through 1995 open heart surgery, was
      performed on 13,285 adult patients. Reoperation necessitated by sternal wound
      complications occurerd in 203 patients (1.5%). The incidence was 1.7% (168/9987)
      after coronary artery bypass grafting (CABG group) and 0.7% (35/3413) after heart
      valve surgery with or without concomitant CABG (HVR group). RESULTS: Factors
      independently related to sternal complications in the CABG group (variable odds
      ratio [95% C.I.]): year of surgery, 1.9 [1.3-2.8] in 1990-1992, 2.0 [1.4-2.9] in
      1993-1995; female sex, 0.4 [0.2-0.6]; diabetic disease, 1.8 [1.2-2.5]; bilateral
      ITA procedure, 3.3 [1.1-7.7]; and postoperative dialysis, 3.1 [1.4-6.9]. In the
      HVR group they were: use of ITA graft, 3.7 [1.7-7.7]; early re-exploration
      because of bleeding 3.0 [1.1-8.2]; and postoperative dialysis 3.1, [1.4-9.3].
      Multivariate models were used to compute the risk for sternal complications in
      each patient. However, the prognostic models based on these risk scores provided
      low sensitivity and low predictive value. Patients with sternal wound
      complications showed no increased early mortality but worse long-term survival
      even after adjustment for other factors (relative hazard in CABG group 1.9 [1.2
      2.8]; in HVR group 2.1 [1.1-4.3]. CONCLUSIONS: The use of ITA grafts seems to be
      one of the most important factors related to sternal wound complications.
      However, patients at truly increased risk for this complication could not be
      identified on the basis of the risk factors considered in this study.

PMID- 9237602
TI  - Beta-blocker effects on postoperative atrial fibrillation.
AB  - OBJECTIVES: To determine whether restarting of Beta Blocker following cardiac
      surgery would reduce the incidence and the severity of post-operative atrial
      fibrillation (AF). METHODS: 210 patients who underwent elective coronary artery
      bypass grafting were randomized to control (C) (n = 105) and Beta Blockers (BB)
      (n = 105) groups. Preoperatively all patients were on one type or another of
      betablockers. Postoperatively only the (BB) group received the medication. Both
      groups were well matched and had the same cardioplegic technique. RESULTS: It was
      found that; (1) post op (AF) developed in 40 patients of group (C) and in 18
      patients of group (BB) P value < 0.02. (2) 73% of (AF) patients in group (C) and
      81% in group (BB) were older than 70 years of age. (3) 76% of the (AF) in (BB)
      group versus 43% in (C) group were converted to sinus rhythm or to a stable
      controlled rhythm within 24 h or less. P value < 0.01. CONCLUSIONS: The results
      indicate that restarting the Beta Blockers in the post-operative period after
      coronary bypass grafts significantly control the incidence and the severity of
      atrial fibrillation. Also it confirms the strong relation between the older age
      and (AF) occurrence.

PMID- 9237603
TI  - Gastric tonometry as a method of visceral oxygenation monitoring in patients
      undergoing coronary revascularisation.
AB  - OBJECTIVE: The aim of the study was to assess gastric mucosal pH during certain
      parts of a major cardiac procedure (hypo- and normothermic), and then throughout
      the first postoperative day. METHODS: Gastric mucosal pH was measured using a
      tonometer, in 15 patients subjected to elective CABG procedures. The patients
      were also assessed haemodynamically and serum lactate concentrations were
      measured. RESULTS: It was found that cardiopulmonary bypass did not suppress
      visceral perfusion. The most critical was the period between 4th and 12th
      postbypass hour when a tendency towards decreased cardiac output and oxygen
      delivery was noted. At the same time oxygen consumption was increasing which
      resulted in triggering of anaerobic metabolic pathways, that was mirrored by
      significant rise in serum lactate levels. During this period of time the lowest,
      although not critical levels of gastric mucosal pH were recorded, suggesting a
      relative decrease in splanchnic perfusion. CONCLUSION: Extracorporeal circulation
      does not significantly compromise splanchnic perfusion. Tonometry is a valuable,
      non-invasive method of visceral oxygenation monitoring. The first postoperative
      day is an especially critical time for a cardiac patient--a frequent control of
      haemodynamic and acid-base balance parameters is absolutely mandatory.

PMID- 9237604
TI  - Early and late outcome of operated and non-operated acute dissection of the
      descending aorta.
AB  - OBJECTIVE: At present debate continues concerning the optimal mode of treatment
      for type B dissections. Controversies are mainly due to discordant results
      regarding survival following medical or surgical treatment. We assessed early and
      long-term outcome of acute dissection of the descending aorta treated by
      emergency aortic replacement, medical treatment or delayed surgery. METHODS:
      Between 1980 and 1995, 225 patients were hospitalized in the medical or surgical
      department of our institution with the diagnosis of acute type B aortic
      dissection. A total of 38 patients (16.8%) underwent replacement of the
      descending aorta within the first week after hospital admission. Primary
      indications for immediate surgery were: rupturing aneurysm (n = 15), diameter of
      the descending aorta (n = 13), malperfusion of the thoracoabdominal aorta (n = 8)
      and pseudocoarctation syndrome with uncontrollable hypertension (n = 2). All
      other patients (n = 187) underwent primary conservative treatment on the
      intensive care unit, including appropriate anti-hypertensive medication. In 12 of
      them, surgery was denied because of age or significant concomitant diseases.
      RESULTS: Hospital mortality after urgent or emergency surgery was 21% (8/38
      patients) for the overall time period. There has been a significant decrease in
      hospital mortality during the last 5 year-period (12% versus 30% between 1980 and
      1994). Causes of death were: cardiac failure in 3, bleeding complications in 2,
      postoperative mesenteric ischemia in 2 and septicemia in one patient. From the 30
      operative survivors, 9 (30%) patients required further surgery on the native
      aorta after a mean follow-up of 48 +/- 13 months. Hospital mortality during
      conservative treatment was 17.6% (33/187 patients). Main causes of death were
      rupture in 14, thoraco-abdominal malperfusion in 13 and cardiac failure in 3
      patients, whereas in 3 patients, the cause of death could not be evaluated. In
      this group, 9 patients had to be shifted to early surgery during the initial
      hospitalization because of impending rupture (n = 4), rapidly increasing diameter
      (n = 2) and suspicion of intestinal ischemia (n = 3). After hospital discharge,
      surgery for chronic dissection was performed in 47 patients, mainly because of
      expanding descending aortic aneurysm. Hospital mortality was 8% (4/47 patients).
      Actuarial survival rates after surgery during the first admission were 85 +/- 6%
      at 5 years and 61 +/- 8% at 10 years, versus 76 +/- 5 and 50 +/- 7% respectively,
      following conservative treatment (P < 0.001). CONCLUSION: Nowadays, acute type B
      dissection can be treated surgically with a reasonable perioperative risk.
      Despite aggressive anti-hypertensive treatment, hospital mortality of primary
      conservative treatment is still high and a substantial percentage of patients
      requires surgery during initial hospitalization. Main causes of death in both
      groups are rupture and abdominal malperfusion: therefore, closed clinical and
      radiologic assessment of the whole thoraco-abdominal aorta is of utmost
      importance. Long-term results are satisfying; unlimited radiographic follow-up
      allows for detection of potential severe complications and for proper planning of
      elective reoperations when indicated.

PMID- 9237605
TI  - Spontaneous pneumothorax from radiographically occult metastatic sarcoma.
AB  - We present two cases of spontaneous pneumothorax secondary to metastatic synovial
      cell sarcoma. Radiographic techniques initially did not suggest lung nodules in
      either patients; thoracoscopy allowed sequential bilateral detection of small
      pulmonary metastases in one case and confirmed the diagnosis during treatment of
      recurrent pneumothorax in the second case. This report underlines that
      pneumothorax may be the first clinical manifestation of metastatic sarcoma and
      can occur even if current imaging techniques are not indicative of metastatic
      disease. In the latter instance, thoracoscopic exploration has to be envisaged in
      order to rule out the possibility of metastatic lung involvement.

PMID- 9237606
TI  - Successful surgical repair of a false aneurysm of the ascending aorta following
      orthotopic cardiac transplantation: a case report.
AB  - A 54-year-old male underwent orthotopic heart transplantation for valvular heart
      and developed a false aneurysm of the ascending aorta at the aortic suture line
      posteriorly 20 months after transplantation. This was successfully repaired using
      a patch of glutaraldehyde-fixed bovine pericardium. At the time of surgical
      repair there was no evidence of infection or atherosclerosis.

PMID- 9237607
TI  - Successful surgery for perforation of the thoracic aorta caused by the tip of an
      intra-aortic balloon pump.
AB  - We describe a case of perforation of the thoracic aorta caused by the tip of an
      intra-aortic balloon pump. The perforation was confirmed by computed tomography
      (CT) scan and immediate surgical repair was successful. Vascular injury due to
      the insertion of an intra-aortic balloon pump is quite common but is
      predominantly confined to limb ischemia or injury to the femoral or iliac artery.
      Iatrogenic aortic perforation leading to significant bleeding is much less common
      and usually fatal.

PMID- 9237608
TI  - Surgical treatment of traumatic rupture of the normal aortic valve.
AB  - Blunt trauma followed by aortic valvular insufficiency is a rare occurence. In
      one case, a male high-school student who had sustained a non-penetrative chest
      injury suffered from aortic regurgitation resulting from the rupture of the
      normal aortic valve. A sizable tear in the non-coronary cusp caused aortic
      insufficiency. The case was treated successfully by surgical replacement of the
      aortic valve with a No. 21 SJM prosthesis.

PMID- 9237609
TI  - Haemodynamic performance of a 16-mm Carbomedics aortic prosthesis.
AB  - A 55-year-old lady underwent repeat aortic valve replacement using a 16-mm
      Carbomedics prosthesis. She made an uneventful postoperative recovery and now
      leads an unrestricted life. Doppler echocardiography reveals a 21-mm Hg gradient
      across the valve at rest. This did not increase with an infusion of 30 mcg/kg per
      min of dobutamine, which resulted in an increase in the cardiac output from 1.96
      to 5.46 l/min.

PMID- 9237610
TI  - Transient neurological deficit immediately after central venous line removal: a
      poorly explained finding.

PMID- 9237611
TI  - 'Christmas tree' cardiac myxoma.

PMID- 9237612
TI  - Model of the c-subunit oligomer in the membrane domain of F-ATPases.
AB  - A model is described of a dodecameric complex consisting of the integral membrane
      component subunit c of the H+-transporting Fo domain of Escherichia coli F
      ATPase. A high-resolution partial structure of monomeric subunit c resulting from
      1H-NMR studies [1] was used for constructing the model. The validity of the
      proposed arrangement of protomers in the dodecameric complex was tested by amino
      acid substitution analysis and chemical, biochemical and genetic data on subunit
      c.

PMID- 9237613
TI  - A transcriptional modification motif encoded by homeobox and fork head genes.
AB  - Homeodomain and fork head domain proteins are thought to act as transcription
      factors by binding to specific DNA target sequences and interacting with other
      proteins. Here I describe a motif which is present in members of both groups of
      transcription factor and which has been shown to modulate their ability to
      activate transcription. The presence of this motif in both homeodomain and fork
      head proteins indicates they may control transcription by a similar molecular
      mechanism, perhaps by interacting with the same cofactors.

PMID- 9237614
TI  - Seryl-phosphorylation of soybean nodule sucrose synthase (nodulin-100) by a Ca2+
      dependent protein kinase.
AB  - Sucrose synthase (SS; EC 2.4.1.13) was radiolabeled in situ by incubating
      detached soybean nodules with 32Pi. Phosphoamino acid analysis indicated that SS
      was phosphorylated on a serine residue(s). In-vitro phosphorylation of purified
      nodule SS by desalted nodule extracts was Ca2+-dependent. This SS-kinase was
      partially purified (approximately 2200-fold) from nodules harvested from
      illuminated plants. The molecular mass of the SS-kinase was about 55,000 on a
      Superdex 75 size-exclusion column or in a denaturing autophosphorylation gel.
      With either purified nodule SS or Syntide 2 as substrate, exogenous calmodulin
      and phosphatidylserine showed little or no effect on the in-vitro activity of
      this partially purified protein kinase. However, its activity was inhibited by W
      7. The purified nodule SS-kinase (or CDPK) phosphorylated nodule PEP carboxylase
      (PEPC; EC 4.1.1.31) in the presence of Ca2+. In contrast, a partially purified
      nodule PEPC-kinase preparation was incapable of phosphorylating nodule SS. Unlike
      nodule PEPC [Zhang et al. (1995) Plant Physiol. 108, 1561-1568], the
      phosphorylation state of SS is not likely modulated in planta by photosynthate
      supply from the shoots.

PMID- 9237615
TI  - Structure of KW-2228, a tailored human granulocyte colony-stimulating factor with
      enhanced biological activity and stability.
AB  - KW-2228 is a tailored human granulocyte colony-stimulating factor (hG-CSF) which
      has more potent granulopoietic activity and is more stable than wild-type hG-CSF.
      Analysis of the 2.3 A resolution crystal structure of KW-2228 unambiguously
      revealed a four-alpha-helix bundle motif with up-up-down-down connectivity. The
      structures of long overhand loops connecting the helices and the N-terminus have
      been definitively determined. The present analysis has clearly revealed that
      substituted residues play important roles in fastening a long overhand loop to
      the N- and C-termini to fix the conformation. This conformation should be
      responsible for a substantial enhancement of the biological activity and
      stability.

PMID- 9237616
TI  - Phosphatidylinositol 4,5-bisphosphate stimulates phosphorylation of the adaptor
      protein Shc by c-Src.
AB  - The adaptor protein Shc was prepared as glutathione S-transferase fusion proteins
      (GST-Shc) and used as in vitro substrate for c-Src. Since phosphotyrosine-binding
      domain of Shc has been shown to bind phosphatidyl-inositol 4,5-bisphosphate
      (PtdIns(4,5)P2) [Zhou et al. (1995) Nature 378, 584-592], effect of PtdIns(4,5)P2
      on the phosphorylation of GST-Shc by c-Src was examined. PtdIns(4,5)P2 stimulated
      the phosphorylation of GST-Shc without any effect on the c-Src activity as judged
      by both its autophosphorylation and phosphorylation of exogenous substrate, Cdc2
      peptide. On the other hand, phosphatidylserine, phosphatidic acid,
      phosphatidylinositol, and phosphatidylinositol 4-phosphate but not
      phosphatidylcholine stimulated the c-Src activity itself. Km for GST-Shc in the
      presence of 1 microM PtdIns(4,5)P2 was calculated to be 90 nM. The PtdIns(4,5)P2
      dependent phosphorylation of GST-Shc was inhibited by a GST-fusion protein
      containing the phosphotyrosine-binding domain of Shc. These results suggest that
      PtdIns(4,5)P2 can act as a regulator of phosphorylation of Shc by c-Src through
      its binding to Shc.

PMID- 9237617
TI  - Effect of polar side chains at position 172 on thermal stability of 3
      isopropylmalate dehydrogenase from Thermus thermophilus.
AB  - To understand the role of the amino acid residue at position 172 in the
      conformational stability, four mutant enzymes of Thermus thermophilus 3
      isopropylmalate dehydrogenase in which Ala172 was replaced with Asp, Glu, Asn,
      and Gln were prepared by site-directed mutagenesis. Three mutants were more
      stable than the wild-type enzyme. No significant change in catalytic properties
      was found in the mutant enzymes. The molecular modeling studies suggested that
      the enhanced thermostability of the mutant enzymes resulted from the formation of
      extra electrostatic interactions and/or improvement of hydrophobic packing of the
      interior core.

PMID- 9237618
TI  - HIV-1 protein Vpr causes gross mitochondrial dysfunction in the yeast
      Saccharomyces cerevisiae.
AB  - The biological effects of the HIV-1 accessory protein, Vpr, have been studied in
      yeast expression systems. In our previous study [1], employing the pCUP1-vpr
      copper-inducible expression cassette, Vpr was shown to cause growth arrest and
      structural defects. In this study yeast constitutively expressing vpr, through
      elevated copy number and/or elevated transcription levels, displayed no growth
      arrest in fermentative growth conditions while Vpr was produced at much lower
      levels than in the inducible expression system. However, such cells were
      respiratory deficient and unable to utilise ethanol or glycerol as the sole
      carbon source. They exhibited gross mitochondrial dysfunction displayed in the
      loss of respiratory chain complex I, II, III, IV and citrate synthase activities.
      The effects on mitochondria required a C-terminal domain of Vpr that contains a
      conserved amino acid sequence motif HFRIGCRHSRIG. These results suggest that the
      widely observed phenomenon of 'Vpr-induced growth arrest' in human cells could be
      due to mitochondrial dysfunction.

PMID- 9237619
TI  - Two functionally distinct myosin heavy chain isoforms in slow skeletal muscle
      fibres.
AB  - The head part of the myosin heavy chain (MHC) represents the essential component
      of the molecular force-generating system of muscle [1-3]. To date, three fast but
      only one slow MHC isoforms have been identified in adult mammalian limb muscles
      [4,5]. We show here two functionally different slow MHC isoforms, MHCIbeta and
      MHCIa, coexisting in a considerable fraction of slow fibres of rabbit plantaris
      muscle. The two isoforms exhibit distinct electrophoretic mobilities and
      different kinetic properties. Thus, as it is known for the fast muscle, also the
      slow muscle seems to use different MHC isoforms in order to fulfil different
      functional demands.

PMID- 9237620
TI  - In vitro expressed dystrophin fragments do not associate with each other.
AB  - Dystrophin, a component of the muscle membrane cytoskeleton, is the protein
      altered in Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD).
      Dystrophin shares significant homology with other cytoskeletal proteins, such as
      alpha-actinin and spectrin. On the basis of its sequence similarity with alpha
      actinin and spectrin, dystrophin has been proposed to function as dimer. However,
      the existence of both dimers and monomers have been observed by electron
      microscopy. To address this apparent discrepancy, we expressed dystrophin
      fragments composed of different domains in an in vitro translation system. The
      expressed fragments were tested for their ability to interact with each other and
      full-length dystrophin by both immunoprecipitation and blot overlay assays. These
      assays were successfully used to demonstrate the dimerization of alpha-actinin
      and spectrin, yet failed to detect any interaction between dystrophin fragments.
      Although these in vitro results do not prove that dystrophin is not a dimer in
      vivo, they do indicate that this interaction is not like that of the alpha
      actinin and spectrin.

PMID- 9237621
TI  - Exogenous, but not endogenous, nitric oxide increases proliferation rates in
      senescent human fibroblasts.
AB  - We investigated the effects of endogenously produced and exogenously applied
      nitric oxide (NO) on cell proliferation rates and cell cycle regulation in
      senescent human fibroblasts (WI38). Induction of inducible nitric oxide synthase
      by tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta inhibited
      cell proliferation and led to a G1 arrest. These effects were partially
      reversible by N(G)-monomethyl-arginine (NMA). Addition of the NO donors sodium
      nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) increased cell
      proliferation rates as well as the S/G2 fraction. This points to a functional
      role of NO in cell cycle regulation and cell proliferation in human fibroblasts
      which depends on the mode of NO generation as well as the culture conditions
      used.

PMID- 9237622
TI  - An improved purification of ECF1 and ECF1F0 by using a cytochrome bo-deficient
      strain of Escherichia coli facilitates crystallization of these complexes.
AB  - A novel strategy, which employs a cytochrome bo-lacking strain (GO104) and a
      modified isolation procedure provides an effective approach for obtaining much
      purer preparations of ECF1F0 than described previously, as well as for isolating
      homogeneous and protein-chemically pure ECF1. ECF1 obtained in this way could be
      crystallized by vapor-diffusion using polyethylene glycol (PEG) as a precipitant
      in a form suitable for X-ray diffraction analysis. The crystals belong to the
      orthorhombic space group P2(1)2(1)2(1), with lattice parameters a = 110, h = 134,
      and c = 269 A, and diffract to a resolution of at least 6.4 A.

PMID- 9237623
TI  - The post-translational modifications of Ral and Rac1 are important for the action
      of Ral-binding protein 1, a putative effector protein of Ral.
AB  - Ral-binding protein 1 (RalBP1) is a putative effector protein of Ral and
      possesses the GTPase-activating activity for Rac1 and CDC42. We examined the
      roles of the post-translational modifications of Ral and Rac1 for the action of
      RalBP1. In COS cells, Ral(G23V), a constitutively active form, was mainly
      detected in the membrane fraction while most of Ral(G23V/C203S), a Ral mutant
      which is not post-translationally modified, was found in the cytosol fraction.
      When RalBP1 was expressed alone in COS cells, it was found in the cytosol but not
      in the membrane fraction. When RalBP1 was coexpressed with Ral(G23V), a part of
      RalBP1 was found in the membrane fraction. However, when RalBP1 was coexpressed
      with Ral(G23V/C203S), all of RalBP1 was recovered in the cytosol fraction.
      Although Ral bound to RalBP1 at a molar ratio of 1:1, the interaction of Ral with
      RalBP1 did not affect the GTPase-activating activity of RalBP1 for Rac1.
      Furthermore, RalBP1 was more active on the post-translationally modified form of
      Rac1 and CDC42 than the unmodified form. These results suggest that the post
      translational modification of Ral is important for the subcellular localization
      of RalBP1 and that the interaction of Ral with RalBP1 is not essential for the
      activity of RalBP1 but plays a role in recruiting RalBP1 to the membrane where
      its substrates, Rac1 and CDC42, reside.

PMID- 9237624
TI  - Modulation of cholinergic locus expression by glucocorticoids and retinoic acid
      is cell-type specific.
AB  - Modulation of mRNA expression of choline acetyltransferase (ChAT) and the
      vesicular acetylcholine transporter (VAChT) by the glucocorticoid dexamethasone
      and by retinoic acid was examined in two neuronal cell lines: basal forebrain
      derived SN56 and pheochromocytoma PC12. Dexamethasone up-regulated ChAT and VAChT
      in SN56 cells, while it had inhibitory effects on these genes in PC12 cells.
      Retinoic acid stimulated the cholinergic markers in both cell types, but in SN56
      cells its effect was partially additive with that of dexamethasone, whereas it
      was much smaller and abrogated by dexamethasone in PC12 cells. Acetylcholine
      content correlated with these mRNA changes. The presence of a glucocorticoid
      response element consensus sequence in the VAChT/ChAT gene locus suggests direct
      transcriptional regulation by glucocorticoids.

PMID- 9237626
TI  - Tyrphostin AG 494 blocks Cdk2 activation.
AB  - We have previously shown that the EGFR kinase selective tyrphostin AG 494 fails
      to inhibit EGFR kinase in intact cells. Yet, AG 494 proved to inhibit EGF- or
      serum-induced cell proliferation (Osherov et al., J. Biol. Chem. 268 (1993) 11134
      11142). In this preliminary communication we show that AG 494 as well as its
      close analogs AG 490 and AG 555 block Cdk2 activation. In contrast, AG 1478, a
      more selective EGFR kinase blocker which is also active as EGFR kinase blocker in
      intact cells, fails to do so. AG 494 exerts its full inhibitory activity on Cdk2
      activation even when added 20 h subsequent to EGF addition when Cdk2 activation
      is maximal. The inhibitory activity on Cdk2 activation parallels its DNA
      synthesis inhibitory activity, strongly suggesting that its target is one of the
      molecular mechanisms involved in Cdk2 activation. AG 494 and its analogs may
      become useful lead compounds for the development of drugs aimed at the cell cycle
      machinery.

PMID- 9237625
TI  - A recombinant polypeptide model of the second nucleotide-binding fold of the
      cystic fibrosis transmembrane conductance regulator functions as an active
      ATPase, GTPase and adenylate kinase.
AB  - CFTR-NBF-2 expressed and purified in fusion with the maltose-binding protein was
      shown to catalyse the reaction ATP-->ADP+Pi by three different assays, monitoring
      ATP turnover, formation of ADP and release of Pi (Km 86 microM, rate constant
      0.37 min(-1)). The reaction product ADP inhibits this ATPase activity. In a
      similar manner the hydrolysis of GTP to GDP and Pi was demonstrated (Km 40
      microM, rate constant 0.29 min(-1)). In the presence of AMP the ATPase reaction
      was superseded by the formation of two ADP from ATP and AMP. As typical for
      adenylate kinases a distinct AMP-binding site could be verified for CFTR-NBF-2 by
      the inability of TNP-ATP and AMP to compete for binding. All three enzymatic
      activities were inhibited by the symmetric double-substrate-mimicking inhibitor
      Ap5A. As NBF-2 plays a central role in CFTR channel opening and closing the
      results reported here are fundamental in understanding mechanisms of CFTR channel
      activity regulation.

PMID- 9237627
TI  - The effects of measles virus persistent infection on AP-1 transcription factor
      binding in neuroblastoma cells.
AB  - Measles virus (MV) persistence in brain cells has broad effects on different
      cellular functions. We have previously shown that NS20Y clone, originally derived
      from C1300 neuroblastoma cells, persistently infected with MV (NS20Y/MS),
      displays constitutively elevated levels of c-fos and PKC mRNAs, implying MV
      mediated effects on transcriptional regulation. Nonetheless, the mode by which
      virus affects the transcriptional machinery still remains obscure. In order to
      define this phenomenon, we studied the binding properties of major transcription
      factors (AP-1 and NFkappaB) in NS20Y/MS cells. Using electrophoretic mobility
      shift approach (EMSA) with the appropriate oligonucleotide probes, we have found
      that the persistent MV infection does not affect NFkappaB binding, while the AP-1
      binding was significantly decreased. Similar inhibition was not observed in NS20Y
      cells acutely infected with MV. Anti-measles antibody-mediated restriction of
      viral gene expression restored AP-1 binding, thus suggesting that measles virus
      proteins may affect the components of the host transcriptional machinery.

PMID- 9237628
TI  - Iron triggers a rapid induction of ascorbate peroxidase gene expression in
      Brassica napus.
AB  - In plants, only ferritin gene expression has been reported to be iron-dependent.
      Here it is demonstrated that an iron overload of Brassica napus seedlings causes
      a large and rapid accumulation of ascorbate peroxidase transcripts, a plant
      specific hydrogen peroxide-scavenging enzyme. This result documents a novel link
      between iron metabolism and oxidative stress. The ascorbate peroxidase mRNA
      abundance was not modified by reducing agents like N-acetyl cysteine, glutathione
      and ascorbate or by pro-oxidants such as hydrogen peroxide or diamide.
      Furthermore, the iron-induced ascorbate peroxidase mRNA accumulation was not
      antagonized by N-acetyl cysteine. Abscisic acid had no effect on the ascorbate
      peroxidase gene expression. Taken together these results suggest that iron
      mediated expression of ascorbate peroxidase gene occurs through a signal
      transduction pathway apparently different from those already described for plant
      genes responsive to oxidative stress.

PMID- 9237629
TI  - DNA helix destabilization by proline and betaine: possible role in the salinity
      tolerance process.
AB  - Evidence is provided for the ability of proline, a salinity induced
      osmoprotectant, to destabilize the double helix and lower the Tm of DNA in a
      concentration dependent manner. At the reported salinity-adaptive bio
      accumulation of 1 M and above, proline could considerably decrease the Tm and
      partially counteract the effect of sodium chloride and spermidine on DNA
      stability. On the contrary, several other amino acids tested did not show any
      such destabilizing effect on DNA helix. Enhanced susceptibility to S1 nuclease
      and insensitivity to DNase I in presence of increasing proline concentrations
      have further suggested a clear destabilization of the double helix. Such an
      effect is somewhat reminiscent of the interaction between betaine, another
      salinity induced osmolyte, and DNA resulting in decreased Tm values. These
      interactions may be significant in view of the abundance of such osmolytes in
      cells under salinity stress-adapted conditions, with many a bacterial mutant
      accumulating them exhibiting improved tolerance to salinity.

PMID- 9237630
TI  - Low temperature perception in plants: effects of cold on protein phosphorylation
      in cell-free extracts.
AB  - Activities of prevalent protein phosphatases decreased by nearly 95% and those of
      individual protein kinases were differentially reduced at low temperature.
      Inhibition of phosphatase activity at temperatures below 12 degrees C resulted in
      marked hyperphosphorylation of a 58-kDa protein (PP58). The temperature threshold
      for hyperphosphorylation of PP58 coincided with the known threshold for cold
      induced calcium influx. Since calcium influx is triggered by several
      environmental stresses, we propose that the observed direct effects of cold on
      the phosphorylation of specific proteins enable cells to couple a shared calcium
      signal to a cold-specific transduction pathway.

PMID- 9237631
TI  - Reduction of thymine hydroperoxide by phospholipid hydroperoxide glutathione
      peroxidase and glutathione transferases.
AB  - Thymine hydroperoxide (5-hydroperoxymethyluracil), a model compound representing
      products of oxidative damage to DNA, is a substrate for glutathione peroxidase
      and some isoforms of glutathione transferase. In this paper, we show that
      selenium-dependent human phospholipid hydroperoxide glutathione peroxidase (Se
      PHGPx) exhibits about four orders of magnitude higher activity on thymine
      hydroperoxide than that of other human enzymes such as selenium-dependent
      glutathione peroxidase and various representatives of glutathione transferases.
      The results indicate that Se-PHGPx may be an important enzyme in repairing
      oxidatively damaged DNA.

PMID- 9237632
TI  - Sequence and characterization of two Arabidopsis thaliana cDNAs isolated by
      functional complementation of a yeast gln3 gdh1 mutant.
AB  - We have isolated two Arabidopsis thaliana cDNAs by complementation of a yeast
      gln3 gdh1 strain that is affected in the regulation of nitrogen metabolism. The
      two clones (RGA1 and RGA2) are homologous to each other and to the SCARECROW
      (SCR) gene that is involved in regulating an asymmetric cell division in plants.
      RGA1, RGA2 and SCR share several structural features and may define a new family
      of genes. RGA1 and RGA2 have been mapped, respectively, to chromosome II and I,
      and their expression in plant is constitutive.

PMID- 9237633
TI  - Mitochondrial function is required for resistance to oxidative stress in the
      yeast Saccharomyces cerevisiae.
AB  - Yeast strains that lack mitochondrial function are sensitive to oxidative stress
      caused by reactive oxygen species (ROS). Specifically, rho0 mutants that lack
      mitochondrial DNA, and strains deleted for the nuclear genes COX6 and COQ3 that
      are required for function of the respiratory electron transport chain, were
      sensitive to H2O2. In addition, treatment with mitochondrial inhibitors including
      antimycin A, oligomycin, potassium cyanide and sodium azide increased sensitivity
      to H2O2. The mechanism does not appear to depend on the antioxidant status of the
      cell since respiratory-deficient strains were able to mount an inducible adaptive
      response to H2O2. We suggest that the oxidant sensitivity is due to a defect in
      an energy-requiring process that is needed for detoxification of ROS or for the
      repair of oxidatively damaged molecules.

PMID- 9237634
TI  - Deletions of the N-terminal regions of the human melanocortin receptors.
AB  - The non-homologous N-terminal regions of four human melanocortin (MC) receptors
      were truncated in order to investigate their putative participation in ligand
      binding. Eleven constructs were made, where different numbers of residues from
      the N terminus were deleted. These constructs were used for transient expression
      experiments in COS cells and analysed by ligand binding. The results show that
      27, 25, 28, and 20 amino acids could be deleted from the N terminus of the human
      MC1, MC3, MC4 and MC5 receptors, respectively, including all potential N-terminal
      glycosylation sites in the MC1 and the MC4 receptors, without affecting ligand
      binding or expression levels. The results indicate that the N-terminal regions of
      the human MC1, MC3, MC4 and MC5 receptors, do not play an important role for the
      ligand binding properties of these receptors.

PMID- 9237635
TI  - Translocation of cytosolic annexin 2 to a Triton-insoluble membrane subdomain
      upon nicotine stimulation of chromaffin cultured cells.
AB  - To gain a better understanding of the function of annexin 2, we have investigated
      the subcellular distribution of the monomeric and heterotetrameric forms of
      annexin 2 and their relationship to the cytoskeleton upon stimulation of
      chromaffin cells. Quantitative immunoblotting has revealed that in resting cells
      a large amount of annexin 2 is monomeric and cytosolic. Upon nicotine stimulation
      80% of total annexin 2 becomes associated with a Triton-X100-insoluble fraction
      where the monomeric and the heterotetrameric forms are found. The translocation
      of monomeric annexin 2 is Ca2+-dependent and complete at 1 microM free Ca2+. We
      have shown that about 66% of the annexin 2 associated with the Triton-X100
      insoluble fraction is soluble in octylglucoside while the remnants are insoluble
      in the detergent and remain likely associated with actin filaments and associated
      cytoskeleton proteins. The octylglucoside-soluble fraction contains integral
      proteins from the plasma membrane and from granule membrane, but does not contain
      caveolin. Moreover, upon nicotine stimulation, a redistribution of proteins was
      detected in this fraction. These dynamic processes appear concomitantly with the
      phosphorylation of annexin 2 in this compartment and with catecholamine release.
      It is suggested that the soluble octylglucoside fraction may represent a special
      lipidic membrane compartment where the NSF attachment proteins and the cytosolic
      proteins like annexin 2 and rab3a may become concentrated upon stimulation of the
      cell. The presence of annexin 2 is consistent with its proposed function on
      granule and target membrane proteins required for the close apposition of two
      distinct membranes and supports its functional role in the regulated
      exocytosis/endocytosis process.

PMID- 9237636
TI  - Medium-reductant directed expression of methyl coenzyme M reductase isoenzymes in
      Methanobacterium thermoautotrophicum (strain deltaH).
AB  - Methanobacterium thermoautotrophicum was grown in a chemostat under various
      controlled conditions in the presence of either sodium sulfide or sodium
      thiosulfate. After establishment of the steady state, cells were taken and
      examined for expression of the mRNA transcripts coding for the different forms of
      methyl coenzyme M reductase (MCR) and methylene tetrahydomethanopterin
      dehydrogenase (MDH). MCR isoenzyme II expression varied most markedly. Expression
      was found not only to depend on known parameters temperature, pH and gassing
      rate, but also on the medium composition, especially the reductant present.

PMID- 9237638
TI  - Proton release from water oxidation by photosystem II: similar stoichiometries
      are stabilized in thylakoids and PSII core particles by glycerol.
AB  - During the four-stepped catalytic cycle of water oxidation by photosystem II
      (PSII) molecular oxygen is released in only one of the four reaction steps
      whereas the release of four protons is distributed over all steps. In principle,
      the pattern of proton production could be taken as indicative of the partial
      reactions with bound water. In thylakoids the extent and rate of proton release
      varies as function of the redox transition and of the pH without concomitant
      variations of the redox pattern. The variation has allowed to discriminate
      between deprotonation events of peripheral amino acids (Bohr effects) as opposed
      to the chemical deprotonation of a particular redox cofactor, and of water. In
      contrast, in thylakoids grown under intermittent light, as well as in PSII core
      particles the pattern of proton release is flat and independent of the pH. This
      has been attributed to the lack in these materials of the chlorophyll a,b-binding
      (CAB) proteins. We now found that a thylakoid-like, oscillatory pattern of proton
      release was restored simply by the addition of glycerol which modifies the
      protein-protein interaction. Being a further proof for the electrostatic origin
      of the greater portion of proton release, this effect will serve as an important
      tool in further studies of water oxidation.

PMID- 9237637
TI  - Direct action of nitric oxide on osteoblastic differentiation.
AB  - The effect of nitric oxide (NO) on osteoblastic differentiation was examined in
      cultured mouse osteoblasts. Interleukin-1beta and tumor necrosis factor-alpha
      expressed inducible NO synthase gene with little effect on constitutive NO
      synthase gene. These cytokines increased NO production, which was inhibited by L
      NMMA pretreatment, and decreased alkaline phosphatase (AIPase) activity, which
      was not restored by L-NMMA. Furthermore, NO donors, sodium nitroprusside and
      NONOate dose-dependently elevated AIPase activity and expression of osteocalcin
      gene. These results suggest that NO directly facilitates osteoblastic
      differentiation and the cytokine-induced inhibition of AIPase activity is
      mediated via mechanism other than NO.

PMID- 9237639
TI  - Chemical modification of alpha2-macroglobulin to generate derivatives that bind
      transforming growth factor-beta with increased affinity.
AB  - alpha2-Macroglobulin (alpha2M) binds a number of cytokines, including
      transforming growth factor-beta1 (TGF-beta1) and TGF-beta2. The affinity of these
      interactions depends on the alpha2M conformation. In this investigation, we
      treated human alpha2M with cis-dichlorodiammineplatinum (II) (cis-Pt), a
      crosslinking reagent that partially 'locks' the alpha2M conformation, and then
      with methylamine to generate a preparation (alpha2M-P/M) consisting of stable
      alpha2M conformational intermediates. alpha2M-P/M bound TGF-beta1 and TGF-beta2
      with higher affinity than any other form of alpha2M studied to date. The
      equilibrium dissociation constants were 14 and 2 nM for TGF-beta1 and TGF-beta2,
      respectively. alpha2M-P/M, at 100 nM, neutralized the activity of TGF-beta1 by
      about 75% in an endothelial cell proliferation assay. The equivalent
      concentration of native alpha2M or methylamine-modified alpha2M had no effect.
      These studies demonstrate that the potential of alpha2M as a cytokine carrier and
      neutralizer may not be fully realized in either the native or completely
      activated conformations.

PMID- 9237640
TI  - Enhanced oxidizability of ubiquinol and alpha-tocopherol during lovastatin
      treatment.
AB  - A double-blinded, placebo-controlled cross-over trial was carried out with 27
      hypercholesterolemic men with coronary heart disease. During the 6-week treatment
      period lovastatin (60 mg/day) decreased fasting serum LDL cholesterol by 45%, LDL
      phosphorus by 38% and apoB by 33%. Ubiquinol content diminished by 13% as
      measured per LDL phosphorus. When LDL was oxidized ex vivo with AMVN both LDL
      ubiquinol and alpha-tocopherol were exhausted faster after lovastatin treatment
      compared to placebo, by 24% (P < 0.005) and 36% (P < 0.0001), respectively. Lag
      time in copper-induced oxidation of LDL decreased by 7% (P < 0.01). This suggests
      diminished antioxidant-dependent resistance of LDL to the early phase of
      oxidative stress.

PMID- 9237641
TI  - Post-transcriptional regulation of inducible nitric oxide synthase mRNA in murine
      macrophages by doxycycline and chemically modified tetracyclines.
AB  - Chemically modified tetracyclines [CMT-3 (IC50 approximately 6-13 microM =
      approximately 2.5-5 microg/ml) and CMT-8 (IC50 approximately 26 microM = 10
      microg/ml), but not CMT-1, -2 or -5], which lack anti-microbial activity,
      inhibited nitrite production in LPS-stimulated macrophages. Unlike competitive
      inhibitors of L-arginine which inhibited the specific activity of inducible
      nitric oxide synthase (iNOS) in cell-free extracts, CMTs exerted no such direct
      effect on the enzyme. CMTs could, however, be shown to inhibit both iNOS mRNA
      accumulation and protein expression in LPS-stimulated cells. Tetracyclines
      (doxycycline and CMT-3) unlike hydrocortisone had no significant effect on murine
      macrophages transfected with iNOS promoter (tagged to a luciferase reporter gene)
      in the presence of LPS. However, doxycycline and CMT-3 augmented iNOS mRNA
      degradation, in LPS-stimulated murine macrophages. These studies show a novel
      mechanism of action of tetracyclines which harbours properties to increase iNOS
      mRNA degradation and decrease iNOS protein expression and nitric oxide production
      in macrophages. This property of tetracyclines may have beneficial effects in the
      treatment of various diseases where excess nitric oxide has been implicated in
      the pathophysiology of these diseases.

PMID- 9237642
TI  - Identification of an intracellular domain of the EGF receptor required for high
      affinity binding of EGF.
AB  - Although all EGF receptors in EGF receptor-expressing cells are molecularly
      identical, they can be subdivided in two different classes that have either a
      high or a low affinity for EGF. Specifically the high-affinity class is
      associated with filamentous actin. To determine whether the interaction of the
      EGF receptor with actin induces its high-affinity state, we studied EGF-binding
      properties of an EGF receptor mutant that lacks the actin-binding site.
      Interestingly, we found that cells expressing this mutant receptor still display
      both high- and low-affinity classes of EGF receptors, indicating that the actin
      binding domain does not determine the high-affinity binding state. By further
      mutational analysis we identified a receptor domain, within the tyrosine kinase
      domain, that regulates the affinity for EGF.

PMID- 9237643
TI  - The conformation of an inhibitor bound to the gastric proton pump.
AB  - Substituted imidazo[1,2-a]pyridines are pharmaceutically important small molecule
      inhibitors of the gastric H+/K+-ATPase, the membrane-bound therapeutic target for
      peptic ulcer disease. A non-perturbing analytical technique, rotational resonance
      NMR spectroscopy, was used to measure a precise (to +/-0.2 A) distance between
      atomic sites in a substituted imidazo[1,2-a]pyridine, TMPIP, bound to H+/K+
      ATPase at its high-affinity site in the intact, native membrane. The structural
      analysis of the enzyme-inhibitor complex revealed that the flexible moiety of
      TMPIP adopts a 'syn-type' conformation at its site of action. Hence, the
      conformation of an inhibitor has been resolved directly under near-physiological
      conditions, providing a sound experimental basis for rational design of many
      active compounds of pharmaceutical interest. Chemically restraining the flexible
      moiety of compounds like TMPIP in the syn-type binding conformation was found to
      increase activity by over 2 orders of magnitude. Such information is normally
      only available after extensive synthesis of related compounds and multiple
      screening approaches.

PMID- 9237644
TI  - Purification and structure of mutacin B-Ny266: a new lantibiotic produced by
      Streptococcus mutans.
AB  - Mutacins are bactericidal substances of proteinaceous nature produced by
      Streptococcus mutans. Lantibiotics are antibacterial substances containing post
      translationally modified amino acids such as lanthionine. Mutacin B-Ny266 was
      purified from the cell pellet of S. mutans strain Ny266 by ethanol extraction at
      pH 2.0 followed by reversed-phase chromatography (Sep-Pak cartridge) and by HPLC
      on a C18 column. The mean purification factor was 3240 +/- 81 and the mean yield
      was 1.0 +/- 0.1%. Molecular mass of mutacin B-Ny266 as determined by mass
      spectroscopy is 2270.29 +/- 0.21 Da. The amino acid sequence of the purified
      active fraction was obtained by Edman degradation after treatment with alkaline
      ethanethiol. Twenty-one amino acids were detected in this analysis. Mutacin B
      Ny266 belongs to the type A lantibiotics. The proposed sequence is: F-K-A-W-U-F-A
      Abu-P-G-A-A-K-O-G-A-F-N-U-Y-A. The molecule differs from that of
      epidermin/staphylococcin 1580 and gallidermin at positions 1, 2, 4, 5 and 6.

PMID- 9237645
TI  - Ligand-free form of human alpha-fetoprotein: evidence for the molten globule
      state.
AB  - By means of circular dichroism and fluorescence spectroscopy, viscometry and
      scanning microcalorimetry we have shown that the release of ligands from human
      alpha-fetoprotein (AFP) results in a considerable rearrangement of the protein
      molecule. Ligand-free form is practically as compact as the native molecule and
      has native-like content of secondary structure but no rigid tertiary structure.
      This means that the release of ligands transforms the AFP molecule into a molten
      globule state. Stripping the ligands from AFP is the irreversible process, i.e.,
      native protein molecule cannot be reconstituted from the ligand-free form of AFP
      by adding back ligands. A possible functional role of such a structural
      transformation is discussed.

PMID- 9237646
TI  - The effect of melittin on proliferation and death of thymocytes.
AB  - The effect of melittin, an activator of phospholipase A2, on proliferation and
      death of rat thymocytes in a broad concentration range was studied. Cell
      proliferation was estimated by the accumulation of colchicin metaphases, necrotic
      death was determined from lysis and staining of cells with trypan blue, and
      apoptosis was assessed from the type of DNA fragmentation, the amount of
      fragmented DNA, and the percentage of cells with subdiploid DNA. It was shown
      that low melittin concentrations (below 5 microg/ml) stimulate thymocyte
      proliferation. At high melittin concentrations, thymocytes die by the primary
      necrosis type. Throughout the concentration range studied, melittin does not
      produce apoptosis in thymocytes. Conversely, high melittin concentrations even
      inhibit thymocyte apoptosis in the control and after irradiation. An inhibitor of
      RNA synthesis actinomycin D does not affect thymocyte death in the presence of
      melittin. It is concluded that the activation of phospholipase A2 can induce
      necrosis but not apoptosis and thus is not a necessary step in the signaling
      cascade that initiates apoptosis in thymocytes.

PMID- 9237647
TI  - Direct evidence that lactogenic hormones induce homodimerization of membrane
      anchored prolactin receptor in intact Nb2-11C rat lymphoma cells.
AB  - The ability of full-size prolactin receptor (PRLR) from Nb2 rat lymphoma cell
      line to undergo lactogenic hormone-induced dimerization in intact cells or in a
      partially purified microsomal fraction was tested. The stoichiometry of ovine
      placental lactogen (oPL) binding to PRLR was documented by SDS-PAGE of the
      covalently cross-linked complexes between [125I]oPL and intact Nb2-11C cells. The
      molecular masses of the specific bands were 82 and 141 kDa, corresponding to
      PRLR:oPL and (PRLR)2:oPL complexes. These results provide direct evidence for the
      occurrence of hormone-induced receptor dimerization in intact cells. Gel
      filtration studies revealed that under non-denaturing conditions, the purified
      receptor forms high-molecular-mass aggregates (190 and 540 kDa) composed of
      receptor dimers and oligomers. Since this aggregation was not dependent on the
      presence of lactogenic hormone, it is possible that the receptor in the intact
      cells may already exist as a noncovalent dimer or oligomer and that hormone
      induced dimerization stabilizes the complex or changes its conformation.

PMID- 9237648
TI  - Purification, amino acid sequence and immunological characterization of Ole e 6,
      a cysteine-enriched allergen from olive tree pollen.
AB  - The Ole e 6 allergen from olive tree pollen has been isolated by combining gel
      permeation and reverse-phase chromatographies. It is a single and highly acidic
      (pI 4.2) polypeptide chain protein. Its NH2-terminal amino acid sequence has been
      determined by Edman degradation. Total RNA from the olive tree pollen was
      isolated, and a specific cDNA was amplified by the polymerase chain reaction
      using a degenerate oligonucleotide primer designed according to the NH2-terminal
      sequence of the protein. The nucleotide sequencing of the cDNA rendered an open
      reading frame encoding a 50 amino acid polypeptide chain, in which two sets of
      the sequential motif Cys-X3-Cys-X3-Cys are present. No sequence similarity has
      been found between this protein and other previously described polypeptides.

PMID- 9237649
TI  - NF-kappaB inhibitors stimulate apoptosis of rabbit mature osteoclasts and inhibit
      bone resorption by these cells.
AB  - Interesting, recent studies have suggested a possibility that transcriptional
      factor NF-kappaB may play a functional role in the survival of mouse osteoclasts.
      However, it has not been known whether NF-kappaB is involved in apoptosis of and
      bone resorption by mature osteoclasts. Thus, using NF-kappaB inhibitors, we
      examined the functional role of NF-kappaB in the induction of apoptosis in rabbit
      mature osteoclasts. PDTC, a potent inhibitor of NF-kappaB, stimulated markedly
      apoptosis of the osteoclasts and inhibited bone resorption by these cells. These
      effects also was observed when three other inhibitors of NF-kappaB were used. And
      a gel mobility shift assay showed that PDTC also inhibited NF-kappaB binding to
      its consensus sequence in the cells. These results suggest a regulatory role for
      NF-kappaB in apoptosis in and bone resorption by rabbit mature osteoclasts.

PMID- 9237650
TI  - Suppression of HIV-1 transcription by beta-chemokines RANTES, MIP1-alpha, and MIP
      1beta is not mediated by the NFAT-1 enhancer element.
AB  - Soluble factors derived from human CD8+ T-lymphocytes inhibit HIV-1 replication
      by suppressing transcription from the viral long terminal repeat (LTR), an effect
      shown to be mediated in part by an NFAT-1 enhancer sequence. We show here that
      the CD8+ derived beta-chemokines, RANTES, MIP1-alpha, and MIP-1beta, known
      suppressors of HIV-1 replication in human peripheral blood mononuclear cells, can
      suppress transcription from the HIV-1 LTR in transient transfection assays in
      cells of the Jurkat (acute T leukemia) line. Surprisingly, the suppression
      mediated by these beta-chemokines persisted in the absence of an intact NFAT-1
      element, suggesting that there are at least two classes of HIV-1 suppressor
      factors--NFAT-1-dependent and NFAT-1-independent factors--produced by CD8+ T
      lymphocytes.

PMID- 9237651
TI  - Identification of a biological inactive complex form of pokeweed antiviral
      protein.
AB  - Pokeweed antiviral protein (PAP) inactivates both eukaryotic and prokaryotic
      ribosomes via a specific depurination of rRNA. The sensitivity of pokeweed
      ribosomes to PAP implies the existence of a mechanism to protect the plant. Using
      monoclonal antibodies specific to PAP, a protein complex (PAPi) which contained
      PAP was identified in leaf extract. In this complex, the enzymatic activity of
      the toxin was strongly inhibited. This protein complex had a pI lower than that
      of PAP and was separated from free PAP by a preparative native gel
      electrophoresis. PAPi had an apparent molecular mass of 57 kDa and was
      dissociated by heating for 5 min at 80 degrees C or by treatment by alkaline or
      acidic pH or by 7 M urea. The other components involved in the complex remain
      unknown.

PMID- 9237652
TI  - The stimulatory effect of negative air ions and hydrogen peroxide on the activity
      of superoxide dismutase.
AB  - The activity of erythrocyte cytosolic superoxide dismutase from rat, bovine, man
      and duck was considerably increased when measured after preparation or incubation
      in media pretreated with negative air ions (mostly superoxide) from
      electroeffluvial ion generator. 0.5-1.0 microM H2O2 was found in incubation
      medium after treatment with air ions. The stimulatory effect of air ions on
      superoxide dismutase activity was mimicked by addition of 0.5-6 microM H2O2. The
      primary physicochemical mechanism of beneficial biological action of negative air
      ions is suggested to be related to the stimulation of superoxide dismutase
      activity by micromolar concentrations of H2O2.

PMID- 9237653
TI  - Protein modification by a Maillard reaction intermediate methylglyoxal.
      Immunochemical detection of fluorescent 5-methylimidazolone derivatives in vivo.
AB  - Methylglyoxal (MG), an endogenous metabolite that increases in diabetes, is a
      common intermediate in nonenzymatic glycation (Maillard reaction) in vivo. Here
      we describe the immunochemical approach to the detection of MG adducts in
      proteins in vitro and in atherosclerotic lesions of human aorta in vivo. The
      reaction of protein (bovine serum albumin) with MG led to selective loss of
      arginine and lysine residues, accompanied by the formation of 5-methylimidazolone
      (N delta-(5-methylimidazolon-2-yl)ornithine) and imidazolysine (1,3-di-lysino-4
      methylimidazole) derivatives, respectively. The anti-5-methylimidazolone antibody
      was prepared by immunizing rabbits with a MG-keyhole limpet hemocyanin conjugate
      and purifying the serum on an affinity gel prepared by covalent attachment of the
      5-methylimidazolone derivative. The antibody cross-reacted with the proteins
      treated with not only MG but trioses, such as hydroxyacetone, dihydroxyacetone,
      and glyceraldehyde. The immunohistochemical analysis revealed that
      atherosclerotic lesions of human aorta contained 5-methylimidazolone derivatives
      whose distributions were identical to those of advanced glycation end products
      (AGEs) detected by the anti-AGE antibody.

PMID- 9237654
TI  - Expressional downregulation of neuronal-type NO synthase I in guinea pig skeletal
      muscle in response to bacterial lipopolysaccharide.
AB  - We have investigated the expression of neuronal-type NO synthase I (NOS I) and
      inducible-type NOS II in guinea pig skeletal muscle (diaphragm). Expression of
      NOS I mRNA and protein was highest in muscle of specific pathogen-free animals,
      lower in normally bred animals, and lowest in lipopolysaccharide (LPS)-treated
      animals. NOS II mRNA and protein levels were highest in muscle of LPS-treated
      animals. Elevated NOS activity in muscle from LPS-treated animals was less
      susceptible to the NOS I-selective inhibitor N(G)-nitro-L-arginine. Expressional
      downregulation of NOS I in sepsis may have implications for contractile function
      of skeletal muscle.

PMID- 9237655
TI  - Conversion of 2',3'-dideoxyadenosine (ddA) and 2',3'-didehydro-2',3'
      dideoxyadenosine (d4A) to their corresponding aryloxyphosphoramidate derivatives
      markedly potentiates their activity against human immunodeficiency virus and
      hepatitis B virus.
AB  - 2',3'-Dideoxyadenosine (ddA), 2',3'-didehydro-2',3'-dideoxyadenosine (d4A) and
      their lipophilic 5'-monophosphate triester (aryloxyphosphoramidate) prodrugs were
      evaluated for their anti-retrovirus and anti-hepatitis B virus activity in
      various cell culture models. The aryloxyphosphoramidate derivatives of ddA (Cf
      1093) and d4A (Cf 1001) showed markedly superior (100-1000-fold) efficacies than
      the parent drugs against human immunodeficiency virus type 1 (HIV-1), HIV-2,
      simian immunodeficiency virus (SIV), Moloney murine sarcoma virus (MSV) and human
      hepatitis B virus (HBV) replication regardless of the cell type in which the
      virus replication was studied (i.e., human T-lymphocyte CEM, MT-4, Molt/4 and
      C8166 cells, peripheral blood lymphocytes (PBL), monocyte/macrophages (M/M),
      murine embryo fibroblasts and human hepatocyte cells). Also the selectivity index
      (ratio of cytotoxic concentration/antivirally effective concentration) of both
      aryloxyphosphoramidate prodrugs was markedly increased. In particular the d4A
      prodrug Cf 1001 showed a selectivity index of 300-3000 as compared with 2-3 for
      the parental d4A in established laboratory cell lines. Also Cf 1001 had a
      selectivity index of 400-650 in HIV-1-infected PBL and M/M, respectively. Both Cf
      1001 and Cf 1093 were equally efficient as 3TC (lamivudine) in inhibiting HBV
      replication in hepatocytes, and rank among the most potent HIV and HBV inhibitors
      reported so far in cell culture.

PMID- 9237656
TI  - Cytosolic NAD+ content strictly depends on ATP concentration in isolated liver
      cells.
AB  - By focusing on the question of the thermodynamic relationships involved in the
      regulation of biological energy conversion, bioenergetic studies usually consider
      the free pyridine and adenine nucleotide rather than their total pools, in either
      cytosol or mitochondria. In this study, we report a new observation that, at
      steady state, nicotinamide nucleotide content is increased by a rise in the ATP
      content of the whole cell under physiological conditions. It is a straight line
      relationship when only NAD+ and ATP are considered. When regarding the
      compartmentation of this phenomenon, it appears that the linear relationship
      between [NAD+] and [ATP] occurs only in the cytosol. Such a dependence could be a
      supplementary mechanism of regulation between various metabolic pathways in the
      liver cell.

PMID- 9237657
TI  - Assembly of Staphylococcus aureus gamma-hemolysin into a pore-forming ring-shaped
      complex on the surface of human erythrocytes.
AB  - Staphylococcal gamma-hemolysin consists of Hlg1 (or Luk F) of 34 kDa and Hlg2 of
      32 kDa, which cooperatively lyse human erythrocytes. Since gamma-hemolysin caused
      swelling of human erythrocytes prior to lysis, we studied pore-forming nature of
      the toxin by use of polyethylene glycols as osmotic protectants and determined
      the functional diameter of the pore. To elucidate the molecular architecture of
      the membrane pore formed by gamma-hemolysin, we solubilized the pore complex with
      2% sodium dodecyl sulfate, separated it from erythrocyte membrane proteins by
      sucrose gradient ultracentrifugation, and observed the isolated complex under an
      electron microscope. Our data showed that Hlg1 and Hlg2 of gamma-hemolysin
      assemble into a ring-shaped 195 kDa complex in a molar ratio of 1 : 1, which may
      form a membrane pore with a functional diameter of 2.1-2.4 nm.

PMID- 9237658
TI  - Differential effects of five types of antipathogenic plant peptides on model
      membranes.
AB  - The effects of five antipathogenic plant peptides, wheat alpha-thionin, potato
      PTH1 defensin, barley LTP2 lipid transfer protein, and potato tuber DL1 and DL2
      defensins, have been tested against phospholipid vesicles (liposomes). Wheat
      thionin very actively induces aggregation and leakage of negatively charged
      vesicles. LTP2 displays the same activities, although to a limited extent. Under
      certain conditions PTH1 and DL2 induce vesicle aggregation, but not leakage.
      Potato defensin DL1 failed to show any effect on liposomes. The same peptides
      have been assayed against a plant pathogenic bacterium, both the membrane-active
      and -inactive compounds having efficient antibacterial action.

PMID- 9237659
TI  - Transfer of CD26/dipeptidyl peptidase IV (E.C. 3.5.4.4) from prostasomes to
      sperm.
AB  - Prostasomes are vesicles present in human semen. They are secreted by the
      prostate and contain large amounts of cholesterol and sphingomyelin. Some of
      their proteins are enzymes. Prostasomes are involved in a number of biological
      functions. In previous papers we demonstrated that lipid can be transferred from
      prostasomes to sperm by a fusion process occurring at neutral or slightly acidic
      pH. In this paper we demonstrate that CD26/dipeptidyl peptidase IV, an enzymatic
      activity absent in sperm, is transferred to sperm from prostasomes. This may be
      of particular interest since, by this procedure, sperm may acquire new membrane
      bound enzymes and modify the catalytic activity of their surface.

PMID- 9237660
TI  - Inhibitors of phosphoprotein phosphatases 1 and 2A cause activation of a 53 kDa
      protein kinase accompanying the apoptotic response of breast cancer cells.
AB  - Treatment of MCF-7 breast cancer cells with 50 nM okadaic acid triggers an
      apoptotic response which is accompanied by a 7-fold increase in the activity of a
      protein kinase with a relative molecular mass of 53 kDa. The activity of the
      kinase was stimulated by cell treatment with inhibitors of phosphoprotein
      phosphatase 1 and 2A, but not by stressing conditions. Okadaic acid-induced
      stimulation of the 53 kDa protein kinase was not abolished by coincubation of
      cells with cycloheximide. We conclude that stimulation of the 53 kDa protein
      kinase by inhibitors of phosphoprotein phosphatases involves pre-existing
      molecular components whose activity depends on the phosphorylation state of
      serine/threonine residues.

PMID- 9237661
TI  - Escherichia coli ccm in-frame deletion mutants can produce periplasmic cytochrome
      b but not cytochrome c.
AB  - Escherichia coli CcmA, CcmB and CcmC polypeptides are required for cytochrome c
      synthesis and are thought to constitute the subunits of an ABC-type transporter
      as judged from sequence data. Using a periplasmic reporter system based on
      Bacillus subtilis cytochrome c-550 and E. coli cytochrome b-562 we show that the
      synthesis of the b-type cytochrome in the periplasm is normal in E. coli ccmA and
      ccmC in-frame deletion mutants. Mutants deleted for ccmF or ccmG encoding a
      component of a putative cytochrome c-heme lyase and a membrane bound thioredoxin
      like protein, respectively, have the same phenotype. The ccm mutants produce
      cytochrome c-550 polypeptide, but not holocytochrome c. Taken together the
      results demonstrate that heme can be transported to the periplasm by a ccm
      independent mechanism.

PMID- 9237662
TI  - Molecular cloning of a novel phosphorylation-dependent inhibitory protein of
      protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in
      smooth muscle.
AB  - The cDNA encoding a phosphorylation-dependent inhibitory protein of protein
      phosphatase-1 (PP1) was isolated from a porcine aorta library. The coding region
      represented the complete amino acid sequence of this protein comprised of a novel
      147-residue polypeptide, which we termed CPI17, a 17-kDa PKC-potentiated
      inhibitory protein of PP1. As well as the native CPI17 from porcine aorta, the
      recombinant protein completely suppressed the PP1 activity (IC50 = 0.18 nM) by
      the stoichiometric thiophosphorylation. The CPI17 mRNA is expressed in smooth
      muscle tissues such as aorta and bladder, whereas little expression was observed
      in heart, skeletal muscle, and non-muscle tissues. These results suggest a
      specific regulatory mechanism of the PP1 activity through CPI17 in smooth muscle.

PMID- 9237663
TI  - Inhibition of protein tyrosine phosphatases causes phosphorylation of tyrosine
      331 in the p60 TNF receptor and inactivates the receptor-associated kinase.
AB  - Inhibition of protein tyrosine phosphatases blocks tumor necrosis factor (TNF)
      induced growth modulation and NF-kappaB activation, both mediated primarily
      through the p60 TNF receptor. How inhibition of the phosphatases affects the p60
      TNF receptor or the recently described receptor-associated serine/threonine
      kinase (p60TRAK) is not known. In this report, we show that this inhibition, when
      induced by pervanadate, caused the tyrosine phosphorylation of the cytoplasmic
      domain (CD) of the p60 receptor, as revealed by phosphoamino acid analysis.
      Furthermore, site-directed mutagenesis indicated that pervanadate specifically
      induced the phosphorylation of tyrosine-331, which is located in the death domain
      of the TNF receptor, a domain to which p60TRAK binds. This tyrosine residue was
      also phosphorylated by purified, recombinant pp60Src in vitro. Inhibition of
      protein tyrosine phosphatases by pervanadate also led to the inactivation of
      p60TRAK. In contrast, okadaic acid, a specific inhibitor of protein
      serine/threonine phosphatase, increased p60TRAK activity. Taken together, these
      results suggest that protein tyrosine phosphatases play an essential role in
      phosphorylation of the cytoplasmic domain of the TNF receptor and in regulation
      of the receptor-associated kinase, and this in turn may play a role in TNF
      mediated growth modulation and NF-kappaB activation.

PMID- 9237664
TI  - The cytokine interleukin-5 (IL-5) effects cotransport of its receptor subunits to
      the nucleus in vitro.
AB  - Interleukin (IL)-5 is central in regulating eosinophilia in allergic disease and
      parasitic infections. We have recently shown that human (h) IL-5 both possesses a
      functional nuclear localization signal capable of targeting a heterologous
      protein to the nucleus and localises to the nucleus of intact receptor-expressing
      cells. In this study, the extracellular domains of the hIL-5 alpha- and beta
      receptor subunits were expressed in baculovirus, fluorescently labelled and
      assayed for nuclear targeting in vitro in the absence and presence of IL-5. The
      beta-subunit, which lacks IL-5 binding activity, only accumulated in the nucleus
      in the presence of both the hIL-5 binding alpha-subunit and hIL-5. The IL-5
      binding alpha-subunit showed similar results. IL-5 thus effected nuclear
      transport of its alpha- and beta-receptor subunits apparently through a 'piggy
      back' mechanism, raising the possibility that IL-5's nuclear signalling role may
      be to cotarget its receptor subunits to the nucleus. This is the first
      demonstration of nuclear protein piggy back transport in vitro.

PMID- 9237665
TI  - Nitric oxide induces apoptosis via triggering mitochondrial permeability
      transition.
AB  - Nitric oxide (NO) induces apoptosis in thymocytes, peripheral T cells, myeloid
      cells and neurons. Here we show that NO is highly efficient in inducing
      mitochondrial permeability transition, thereby causing the liberation of
      apoptogenic factors from mitochondria which can induce nuclear apoptosis (DNA
      condensation and DNA fragmentation) in isolated nuclei in vitro. In intact
      thymocytes, NO triggers disruption of the mitochondrial transmembrane potential,
      followed by hypergeneration of reactive oxygen species, exposure of phosphatidyl
      serine on the outer plasma membrane leaflet, and nuclear apoptosis. Inhibitors of
      mitochondrial permeability transition such as bongkrekic acid and a cyclophilin D
      binding cyclosporin A derivative, N-methyl-Val-4-cyclosporin A, prevent the
      mitochondrial as well as all post-mitochondrial signs of apoptosis induced by NO
      including nuclear DNA fragmentation and exposure of phosphatidylserine residues
      on the cell surface. These findings indicate that NO can cause apoptosis via
      triggering of permeability transition.

PMID- 9237666
TI  - Molecular cloning and expression pattern of rpr-1, a resiniferatoxin-binding,
      phosphotriesterase-related protein, expressed in rat kidney tubules.
AB  - Bacterial phosphotriesterases are enzymes that hydrolyse phosphotriester
      containing organophosphate pesticides. Resiniferatoxin is a vanilloid that
      desensitises nociceptive neurons. By screening a rat cDNA library with labelled
      resiniferatoxin, we unexpectedly isolated a novel rat phosphotriesterase
      homologue, here named rpr-1, that encodes a 349 amino acid, 39 kDa protein
      (confirmed by in vitro translation). Northern blotting and in situ hybridisation
      show expression primarily in proximal tubules of the kidney, in which rpr-1
      distribution correlates with resiniferatoxin-binding activity. These results
      suggest an unsuspected link between the phosphotriesterase enzyme family and
      resiniferatoxin toxicity and pharmacology.

PMID- 9237668
TI  - Extracellular Mg2+ regulates the intracellular Na+ concentration in rat
      sublingual acini.
AB  - The intracellular free Na+ concentration ([Na+]i) increases during muscarinic
      stimulation in salivary acinar cells. The present study examined in rat
      sublingual acini the role of extracellular Mg2+ in the regulation of the
      stimulated [Na+]i increase using the fluorescent sodium indicator benzofuran
      isophthalate (SBFI). The muscarinic induced rise in [Na+]i was approximately 4
      fold greater in the absence of extracellular Mg2+. When Na+ efflux was blocked by
      the Na+,K+-ATPase inhibitor ouabain, the stimulated [Na+]i increase was
      comparable to that seen in an Mg2+-free medium. Moreover, ouabain did not add
      further to the stimulated [Na+]i increase in an Mg2+-free medium suggesting that
      removal of extracellular Mg2+ may inhibit the Na+ pump. In agreement with this
      assumption, ouabain-sensitive Na+ efflux and rubidium uptake were reduced by
      extracellular Mg2+ depletion. Our results suggest that extracellular Mg2+ may
      regulate [Na+]i in sublingual salivary acinar cells by modulating Na+ pump
      activity.

PMID- 9237667
TI  - Dramatic enhancement of the specific expression of the heart-type fatty acid
      binding protein in rat brown adipose tissue by cold exposure.
AB  - To understand the difference in energy metabolisms in brown (BAT) and white (WAT)
      adipose tissues, we examined the steady-state transcript levels of the heart-type
      and adipose-type fatty acid binding proteins (H-FABP and A-FABP, respectively) by
      Northern blot analysis. The transcript of H-FABP in rat BAT was increased about
      100-fold by cold exposure, whereas that in WAT was negligible, and was increased
      only slightly by cold exposure. The transcript of A-FABP was observed in both BAT
      and WAT, the level being slightly greater in WAT. However, its transcript level
      was not affected by cold exposure in either adipose tissue. In addition, on
      treatment with norepinephrine (NE), transcript level of H-FABP was elevated
      markedly but that of A-FABP was not changed in rat brown adipocytes. Therefore,
      the stimulatory effect of cold exposure on the transcript of H-FABP in BAT was
      concluded to be mediated by NE, like that of the uncoupling protein (UCP). Thus,
      the expressions of H-FABP and UCP may be controlled by the same mechanism.

PMID- 9237669
TI  - An inactive mutant of the alpha subunit of protein kinase CK2 that traps the
      regulatory CK2beta subunit.
AB  - Protein kinase CK2 (casein kinase 2) is a ubiquitous Ser/Thr protein kinase
      involved in cell proliferation. Mutation of the alpha subunit of the Xenopus
      laevis CK2 to change aspartic acid 156 to alanine (CK2alphaA156) resulted in an
      inactive enzyme. The CK2alphaA156 mutant, however, binds the regulatory subunit
      as measured by retention of beta on a nickel chelating column mediated by (His)6
      tagged CK2alphaA156. Addition of CK2alphaA156 also caused beta to shift
      sedimentation in a sucrose gradient from a beta2 dimer (52 kDa) to an alpha2beta2
      tetramer (130,000 kDa). CK2alphaA156 can trap the beta subunit in an inactive
      complex reducing the stimulation of casein phosphorylation caused by addition of
      beta to wild-type alpha. This competitive effect depends on the ratio of
      alpha/alphaA156 and on the amount of beta available. Since beta inhibits the
      phosphorylation of calmodulin by CK2alpha, the addition of CK2alphaA156, in this
      case, increases calmodulin phosphorylation by the alpha and beta combination.
      These results suggest that CK2alphaA156 may be a useful dominant-negative mutant
      that can serve to explore the multiple functions of CK2beta.

PMID- 9237670
TI  - Restriction of intramolecular movements within the Cry1Aa toxin molecule of
      Bacillus thuringiensis through disulfide bond engineering.
AB  - Disulfide bridges were introduced into CrylAa, a Bacillus thuringiensis
      lepidopteran toxin, to stabilize different protein domains including domain I
      alpha-helical regions thought to be involved in membrane integration and
      permeation. Bridged mutants could not form functional ion channels in lipid
      bilayers in the oxidized state, but upon reduction with beta-mercaptoethanol,
      regained parental toxin channel activity. Our results show that unfolding of the
      protein around a hinge region linking domain I and II is a necessary step for
      pore formation. They also suggest that membrane insertion of the hydrophobic
      hairpin made of alpha-helices 4 and 5 in domain I plays a critical role in the
      formation of a functional pore.

PMID- 9237671
TI  - Spectral studies on the calcium-binding properties of Mts1 protein and its
      interaction with target protein.
AB  - Two calcium-binding sites of the Mts1 protein, a member of S-100 protein family,
      were distinguished with the Fluo-3 fluorescent technique. The geometric mean of
      the apparent dissociation constant (Kd) for these two sites is 2.6 microM; the
      Hill coefficient (nH) is 0.98. In the presence of a novel target protein p37,
      isolated from the mouse adenocarcinoma cell line CSML-100, Mts1 binds Ca2+ ions
      with higher affinity and with strong positive cooperativity (Kd = 0.2 microM, nH
      = 1.91). Interaction of Mts1 with p37 is confirmed by the fluorescent probe 2-p
      toluidinylnaphthalene-6-sulfonate (TNS). Reaction with TNS shows that p37
      interacts with the hydrophobic site of Mts1 which is exposed due to the binding
      of Ca2+ ions.

PMID- 9237672
TI  - Cloning and functional expression of human kynurenine 3-monooxygenase.
AB  - Kynurenine 3-monooxygenase, an NADPH-dependent flavin monooxygenase, catalyses
      the hydroxylation of L-kynurenine to L-3-hydroxykynurenine. By hybridization
      screening using a cDNA probe encoding the entire exon 2 of Drosophila
      melanogaster kynurenine 3-monooxygenase, we isolated a 2.0 kb cDNA clone coding
      for the corresponding human liver enzyme. The deduced amino acid sequence of the
      human protein consists of 486 amino acids with a predicted molecular mass of
      55,762 Da. Transfection of the human cDNA in HEK-293 cells resulted in the
      functional expression of the enzyme with kinetic properties similar to those
      found for the native human protein. RNA blot analysis of human tissues revealed
      the presence of a major mRNA species of approximately 2.0 kb in liver, placenta
      and kidney.

PMID- 9237673
TI  - Overlapping sites on the Link module of human TSG-6 mediate binding to hyaluronan
      and chrondroitin-4-sulphate.
AB  - Link modules are hyaluronan-binding domains that are involved in the formation
      and stability of extracellular matrix and cell migration. We have examined the
      glycosaminoglycan specificity of the Link module from the arthritis-associated
      protein, human TSG-6, by microtitre plate-based assays employing biotinylated
      hyaluronan or mono-biotinylated Link module. This domain was found to interact
      specifically with chondroitin-4-sulphate (C4S), with similar affinity to
      hyaluronan, but not with chondroitin-6-sulphate or heparin. Competition
      experiments indicate that C4S and hyaluronan have overlapping binding surfaces on
      the TSG-6 Link module. Disease-associated changes in C4S expression may influence
      the localisation and biological role of TSG-6.

PMID- 9237674
TI  - Activation of translation initiation factor eIF2B by insulin requires
      phosphatidyl inositol 3-kinase.
AB  - Eukaryotic initiation factor eIF2B mediates a key regulatory step in peptide
      chain initiation and is acutely activated by insulin, although, it is not clear
      how. Inhibitors of phosphatidylinositide 3-kinase blocked activation of eIF2B,
      although rapamycin, which inhibits the p70 S6 kinase pathway, did not.
      Furthermore, a dominant negative mutant of PI 3-kinase also prevented activation
      of eIF2B, while a Sos-mutant, which blocks MAP kinase activation, did not. The
      data demonstrate that a pathway distinct from MAP and p70 S6 kinases regulates
      eIF2B. Glycogen synthase kinase-3 (GSK-3) phosphorylates and inactivates eIF2B.
      In all cases, eIF2B and GSK-3 were regulated reciprocally. Dominant negative PI 3
      kinase abolished the insulin-induced inhibition of GSK-3. These data strongly
      support the hypothesis that insulin activates eIF2B through a signalling pathway
      involving PI 3-kinase and inhibition of GSK-3.

PMID- 9237675
TI  - Effect of triphosphate modifications in 2'-deoxynucleoside 5'-triphosphates on
      their specificity towards various DNA polymerases.
AB  - Some natural and glycon-modified dNTPs with beta,gamma-pyrophosphate substitution
      at the triphosphate residue were synthesized and studied to evaluate the effect
      of these modifications on substrate properties of dNTPs in DNA synthesis
      catalyzed by human placental DNA polymerases alpha and beta, avian myeloblastosis
      virus reverse transcriptase, and calf thymus terminal deoxynucleotidyl
      transferase. Reverse transcriptase proved to be the enzyme least specific to such
      modifications; the substrate activity of beta,gamma-methylenediphosphonate
      substituted dTTP and 3'-azido-3'-deoxy-dTTP decreased in the following order: CF2
      = CHF > CBr2 > CFMe >> CH2. This order is individual for each DNA polymerase. It
      is interesting to mention that beta,gamma-CBr2 substituted dTTP is neither a
      substrate nor an inhibitor of DNA polymerase beta. This specificity distinguishes
      DNA polymerase beta from other DNA polymerases studied.

PMID- 9237676
TI  - Isolation and characterization of biliprotein aggregates from Acaryochloris
      marina, a Prochloron-like prokaryote containing mainly chlorophyll d.
AB  - Phycobiliprotein aggregates were isolated from the prokaryote Acaryochloris
      marina, containing chlorophyll d as major pigment. In the electron microscope the
      biliprotein aggregates appear as rod-shaped structures of 26.0 x 11.3 nm,
      composed of four ring-shaped subunits 5.8 nm thick and 11.7 nm in diameter.
      Spectral data indicate that the aggregates contain two types of biliproteins:
      phycocyanin and an allophycocyanin-type pigment, with very efficient energy
      transfer from the phycocyanin- to allophycocyanin-type constituent. The
      chromophore-binding polypeptides of the pigments have apparent molecular masses
      of 16.2 and 17.4 kDa. They crossreact with antibodies against phycocyanin and
      allophycocyanin from a red alga.

PMID- 9237677
TI  - Light-harvesting in Acaryochloris marina--spectroscopic characterization of a
      chlorophyll d-dominated photosynthetic antenna system.
AB  - Oxygenic photosynthesis of the prokaryote Acaryochloris marina involves
      chlorophyll d (Chl d) as the major pigment [Miyashita et al. (1996) Nature 383,
      402]. Four spectral forms of Chl d (peak wavelengths: 694, 714, 726 and 740 nm)
      are resolvable by low-temperature absorption spectroscopy on intact cells. Based
      on fluorescence spectra (at 290 K and 77 K) and on analysis of fluorescence
      induction curves we conclude: (1) excitation energy is efficiently transferred
      between the various spectral forms of Chl d and the PS II reaction center; (2)
      Chl d serves as a light-harvesting pigment for both, Photosystem II (PS II) and
      PS I; (3) excitation energy transfer between PS II units occurs.

PMID- 9237678
TI  - The leech excitatory peptide, a member of the GGNG peptide family: isolation and
      comparison with the earthworm GGNG peptides.
AB  - A member of the GGNG peptide family was isolated from Hirudo nipponia (leech).
      GGNG peptides had only been isolated previously from earthworms. The C-terminus
      structure of the leech peptide, LEP (leech excitatory peptide), was -Gly-Gly-Asn
      amide, while that of the earthworm peptides, EEP (earthworm excitatory peptide),
      was -Gly-Gly-Asn-Gly. LEP exerted 1000-fold more potent activities on leech gut
      than did EEP-2. On the other hand, EEP-2 was 1000-fold more potent than LEP on
      the crop-gizzard of the earthworm. Analog peptides of LEP and EEP-2 were
      synthesized, and the myoactive potency of each analog on the leech and earthworm
      tissues was compared.

PMID- 9237679
TI  - Human free secretory component is composed of the first 585 amino acid residues
      of the polymeric immunoglobulin receptor.
AB  - The main objective of this work was to unequivocally determine the C-terminal
      sequence of human milk free secretory component (SC). It was found to end at
      arginine-585, i.e. 33 amino acids downstream from the major heterogeneous C
      terminal residue previously identified for colostrum SC. In contrast, our data
      showed that the C-terminal end of SC was found to be homogeneous. Conflicting
      assignments, Asp/Gln, a missing Asn-211, Asp/Asn, Glu/Gln were corrected and
      found to agree with the cDNA sequence. An Ala/Val substitution at position 562
      (domain VI) was identified. Its genetic significance is uncertain at present.

PMID- 9237681
TI  - Metabolic analysis of S. cerevisiae strains engineered for malolactic
      fermentation.
AB  - A complete malolactic fermentation was achieved using Saccharomyces cerevisiae
      strains coexpressing the genes mleS and mae1 coding for the Lactococcus lactis
      malolactic enzyme and the Schizosaccharomyces pombe malate permease under the
      control of yeast promoters. The expression level of mae1 greatly influences the
      kinetics of the reaction by controlling the rate of malate uptake meanwhile a
      high expression level of mleS induces a partial consumption of malate derived
      from glucose by the malolactic enzyme. A strain expressing several copies of mae1
      and one copy of mleS degrades 3 g/l of malate almost exclusively through the
      malolactic pathway in 4 days under enological conditions, without metabolic side
      effects.

PMID- 9237680
TI  - Identification of the yeast ARG-11 gene as a mitochondrial ornithine carrier
      involved in arginine biosynthesis.
AB  - The ARG-11 gene in Saccharomyces cerevisiae encodes a protein with the
      characteristic features of a family of 35 related membrane proteins that are
      encoded in the fungal genome. Some of them are known to transport various
      substrates and products across the inner membranes of mitochondria, but the
      functions of 29 members of the family are unknown. The yeast ARG-11 protein has
      been over-produced as inclusion bodies in Escherichia coli. It has been
      solubilized in the presence of sarkosyl, re-constituted into liposomes and shown
      to transport ornithine in exchange for protons. Its main physiological role is
      probably to take ornithine synthesized from glutamate in the mitochondrial matrix
      to the cytosol where it is converted to arginine.

PMID- 9237682
TI  - Evidence for a crosslink between c-heme and a lysine residue in cytochrome P460
      of Nitrosomonas europaea.
AB  - Cytochrome P460 and hydroxylamine oxidoreductase (HAO) of Nitrosomonas europaea
      catalyze the oxidation of hydroxylamine. Cytochrome P460 contains an unidentified
      heme-like chromophore whose distinctive spectroscopic properties are similar to
      those for the P460 heme found in HAO. The heme P460 of HAO has previously been
      shown by protein chemistry and NMR structural analysis to be a c-heme with an
      additional covalent crosslink between the C2 ring carbon of a tyrosine residue of
      the polypeptide chain and a meso carbon of the porphyrin [Arciero, D.M. et al.
      (1993) Biochemistry 32, 9370-9378]. The recent determination of the gene sequence
      for cytochrome P460 [Bergmann, D.J. and Hooper, A.B. (1994) FEBS Lett. 353, 324
      326] indicates that the heme in this protein also possesses a c-heme binding site
      and provides the basis for determining whether an HAO-like crosslink exists to
      the porphyrin. Sequence analysis of a purified heme-containing tryptic
      chromopeptide from cytochrome P460 revealed two predominant amino acid residues
      per cycle. Two peptides present in the chromopeptide with the sequences
      NLPTAEXAAXHK and DGTVTVXELVSV. Comparison of the data to the gene sequence for
      the protein revealed that the gaps in the first peptide (indicated by X's) code
      for C residues, confirming the prediction of a c-heme binding motif. The gap in
      the sequence in the second peptide at cycle 7 is predicted by the gene sequence
      to be a K. The results suggest that the lysine residue is crosslinked in some
      manner to the porphyrin macrocycle, possibly mimicking the tyrosine crosslink
      found for the heme P460 of HAO. While a common role for the crosslinked residues
      in HAO and cytochrome P460 is difficult to ascertain due to the dissimilarities
      in side chain structure, it may be related to the similar pKa values for lysine
      and tyrosine.

PMID- 9237683
TI  - RNA polymerase I from S. cerevisiae depends on an additional factor to release
      terminated transcripts from the template.
AB  - Terminated transcripts were generated at the ends of linearized DNA templates and
      at DNA-bound lac repressor by in vitro transcription with highly enriched or
      purified yeast RNA polymerase I (pol I). The release of the synthesized
      transcripts from the DNA was analyzed using immobilized DNA as template for the
      transcription reaction. An additional activity distinguishable from pol I was
      necessary to remove the terminated RNA from the template. Efficiency of
      transcript release could be improved if a thymidine-rich DNA fragment was located
      upstream of the transcriptional arrest caused by the DNA-bound lac repressor. The
      release activity interacted with different forms of polymerases, pol I able to
      initiate on the ribosomal gene promoter and pol I only active in non-specific
      transcription.

PMID- 9237684
TI  - Decrease of rotenone inhibition is a sensitive parameter of complex I damage in
      brain non-synaptic mitochondria of aged rats.
AB  - We investigated NADH oxidation in non-synaptic and synaptic mitochondria from
      brain cortex of 4- and 24-month-old rats. The NADH oxidase activity was
      significantly lower in non-synaptic mitochondria from aged rats; we also found a
      significant decrease of sensitivity of NADH oxidation to the specific Complex I
      inhibitor, rotenone. Since the rotenone-binding site encompasses Complex I
      subunits encoded by mtDNA, these results are in accordance with the mitochondrial
      theory of aging, whereby somatic mtDNA mutations are at the basis of cellular
      senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the
      aged animals.

PMID- 9237685
TI  - Nitric oxide donors activate the cyclo-oxygenase and peroxidase activities of
      prostaglandin H synthase.
AB  - Prostaglandin H synthase (PHS) is a dual enzyme with cyclo-oxygenase and
      peroxidase activities. The nitric oxide (NO) donors, sodium nitroprusside (SNP),
      S-nitroso-N-acetylpenicillamine (SNAP) and spermine NONOate (SPER/NO), activated
      both cyclo-oxygenase and peroxidase activities of PHS. SNP activated PHS by
      increasing Vmax without affecting Km, the activation constants being 1.0 mM for
      cyclo-oxygenase and 1.3 mM for peroxidase. Analysis of progress curves and
      absorption spectra of PHS suggested that NO released from SNP interacted with the
      heme at the active site of the enzyme. Moreover, SNP counteracted the peroxide
      induced inactivation of PHS, suggesting that the interplay between the
      intracellular peroxide and NO is critical in tuning PHS activity in cells.

PMID- 9237686
TI  - Cell-cycle-dependent phosphorylation of the basal transcription factor RAP74.
AB  - In this report, cell-cycle-dependent effects of TFIID on other basal
      transcription factors were investigated. We purified TFIID fractions from HeLa
      cells synchronized in the S/G2 phases and in early G1 phase, and show that RAP74
      is phosphorylated more highly by the S/G2 phase TFIID fraction than by the early
      G1 phase TFIID fraction. Further analyses using deletion mutants of RAP74
      revealed that amino acid residues 206-256 are phosphorylated by the TFIID
      fraction. Reconstitution of in vitro transcription activity indicates that the
      cell-cycle-dependent phosphorylation of RAP74 increases TFIIF transcription
      activity.

PMID- 9237687
TI  - Advanced glycation endproducts stimulate the MAP-kinase pathway in tubulus cell
      line LLC-PK1.
AB  - Advanced glycation endproducts (AGEs) are suggested to play an important role in
      diabetic nephropathy. They induce specific cellular responses such as the release
      of cytokines in different cell lines. The effect of AGEs on signal transduction
      pathways was investigated in the renal tubulus cell line LLC-PK1. Using a serine
      phosphate-specific antibody AGE-induced cellular responses associated with
      phosphorylation/dephosphorylation events were demonstrated. In particular, the
      p42MAP kinase and its downstream target, the AP-1 complex, are shown to be
      activated by AGE-BSA but not by BSA. In contrast, only partial phosphorylation is
      observed for the p70S6-kinase. Thus, AGEs appear to induce specific signal
      transduction pathways.

PMID- 9237688
TI  - Hedgehog and patched gene expression in adult ocular tissues.
AB  - We analysed the expression of members of the hh gene family in adult ocular
      tissues of newt, frog and mouse by RT-PCR method. Shh displayed restricted
      expression in the neural retina that was conserved in each species analyzed. X
      bhh, X-chh and mouse Ihh were detected in the iris and in the retinal pigment
      epithelium, while mouse Dhh was detected additionally in the neural retina and
      faintly in the cornea. We also found that two types of ptc genes, potential hh
      targets and receptors, were expressed in these tissues, suggesting the presence
      of active hh signalling there.

PMID- 9237689
TI  - cDNA cloning of Clavanins: antimicrobial peptides of tunicate hemocytes.
AB  - Clavanins are a family of alpha-helical antimicrobial peptides found in hemocytes
      of the tunicate, Styela clava. We examined a cDNA library prepared from
      pharyngeal tissues of S. clava and sequenced 24 clones that encoded
      prepropeptides of Clavanins A, C, D or E. These sequences indicated that
      Clavanins are synthesized as 9.2 kDa prepropeptides which contain a 19-residue
      signal peptide, followed in turn by a highly polar 'pro' region (LEERKSEEEK) with
      five glutamic acid residues, the 23 residues of the mature Clavanin peptide, the
      glycine residue needed for its amidation and a 27-residue polar C-terminal
      extension that is removed in later processing. Although the signal sequence and
      anionic propiece of Clavanin precursors share features with corresponding regions
      in precursors of the certain frog peptides, including ranalexin, gaegurins,
      dermaseptins and deltorphins, their unique multipartite structure suggests that
      they are not actually homologues of these amphibian peptides.

PMID- 9237690
TI  - Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and
      its association with heat shock protein Hsp27.
AB  - Protein kinase B (PKB, also named as Akt or RAC-protein kinase), that is
      activated by cellular stress such as heat shock and hyperosmotic treatment, was
      revealed to be activated by oxidative stress and by chemical stressors of CdCl2
      and NaAsO2 by measuring the activity of the enzyme immunoprecipitated from the
      transfected COS-7 cells. Upon stress treatment, a 30-kDa phosphoprotein was co
      immunoprecipitated with PKB from the cells metabolic labeled with
      [32P]orthophosphate. The phosphoprotein was identified as Hsp27, a small heat
      shock protein, by immunoblot analysis and co-immunoprecipitation. The association
      of Hsp27 was specific to PKB as the heat shock protein was not co
      immunoprecipitated with other protein kinases such as protein kinase C and PKN.
      When the cells were treated with H2O2, PKB was activated gradually and the
      association of Hsp27 with PKB increased concurrently with the enhancement of PKB
      activity. In heat-shocked cells, activation of PKB and the association of Hsp27
      were detected immediately after the treatment, and the association of the heat
      shock protein decreased while PKB kept stimulated activity when the cells were
      further incubated at 37 degrees C. These results suggest that Hsp27 is involved
      in the activation process of PKB in the signal transduction pathway of various
      forms of stress.

PMID- 9237691
TI  - Centrifugation does not alter spatial distribution of 'BEP4' mRNA in
      paracentrotus lividus EGG.
AB  - Paracentrotus lividus unfertilized eggs were centrifuged in a sucrose gradient,
      so to split each into two parts: a nucleated light fragment and an anucleated
      heavy fragment. Northern blot analyses utilizing a bep4 probe as animal marker
      and H2A histone gene and 12S-mit RNA as controls indicate that the eggs are
      elongated along the animal-vegetal axis during centrifugation and thereafter
      split into an animal and a vegetal half. Treatment of the eggs with colchicine
      before centrifugation abolishes the animal localization of bep4 mRNA.

PMID- 9237693
TI  - Partial purification and characterization of the DNA polymerase from the
      cyanelles of Cyanophora paradoxa.
AB  - A DNA polymerase was partially purified and characterized from the photosynthetic
      organelles (cyanelles) of the protist, Cyanophora paradoxa. While cyanelles have
      several cyanobacterial features, such as a lysozyme-sensitive cell wall,
      unstacked thylakoids and light harvesting phycobilisomes, their genome size and
      structure resemble those of chloroplasts, suggesting that cyanelles occupy a
      unique intermediate position between chloroplasts and their phylogenetic
      ancestors, the cyanobacteria. When comparing the biochemical characteristics of
      the cyanelle DNA polymerase to those of its counterparts from higher plant
      chloroplasts and from a cyanobacterium, it is clear that the cyanelle enzyme
      resembles chloroplast DNA polymerases which are eukaryotic gamma-type enzymes.

PMID- 9237692
TI  - Crystal structure of Escherichia coli inorganic pyrophosphatase complexed with
      SO4(2-). Ligand-induced molecular asymmetry.
AB  - The three-dimensional structure of inorganic pyrophosphatase from Escherichia
      coli complexed with sulfate was determined at 2.2 A resolution using Patterson's
      search technique and refmed to an R-factor of 19.2%. Sulfate may be regarded as a
      structural analog of phosphate, the product of the enzyme reaction, and as a
      structural analog of methyl phosphate, the irreversible inhibitor. Sulfate binds
      to the pyrophosphatase active site cavity as does phosphate and this diminishes
      molecular symmetry, converting the homohexamer structure form (alpha3)2 into
      alpha3'alpha3". The asymmetry of the molecule is manifested in displacements of
      protein functional groups and some parts of the polypeptide chain and reflects
      the interaction of subunits and their cooperation. The significance of re
      arrangements for pyrophosphatase function is discussed.

PMID- 9237694
TI  - A new role for enteric glucagon-37: acute stimulation of glucose absorption in
      rat small intestine.
AB  - Glucagon-37 is secreted by intestinal L-cells following carbohydrate uptake. It
      is known to inhibit gastric acid secretion (hence also named oxyntomodulin) and
      appears to increase intracellular cyclic AMP concentrations. Since cyclic AMP
      could enhance intestinal glucose absorption, a possible stimulatory effect of
      glucagon-37 on glucose transport was examined. Glucagon-37 acutely increased
      glucose absorption in the isolated, vascularly perfused small intestine and in
      isolated enterocytes of the rat. In these cells the stimulation by glucagon-37
      could be completely blocked by the cAMP antagonist Rp-cAMPS and was therefore
      mediated by cAMP. The stimulation of intestinal glucose absorption by glucagon-37
      appears to be a major new physiological function.

PMID- 9237695
TI  - Early clinical and laboratory indicators of acute dengue illness.
AB  - A prospective observational study was conducted to identify early indicators of
      acute dengue virus infection. Children with fever for <72 h without obvious cause
      were studied at hospitals in Bangkok and Kamphaeng Phet, Thailand, until
      resolution of fever. Of 172 evaluable subjects (91% of enrollees), 60 (35%) had
      dengue, including 32 with dengue fever (DF) and 28 with dengue hemorrhagic fever
      (DHF). At enrollment, children with dengue were more likely than children with
      other febrile illnesses (OFI) to report anorexia, nausea, and vomiting and to
      have a positive tourniquet test, and they had lower total white blood cell
      counts, absolute neutrophil and absolute monocyte counts, and higher plasma
      alanine and aspartate (AST) aminotransferase levels than children with OFI.
      Plasma AST levels were higher in children who developed DHF than in those with
      DF. These data identify simple clinical and laboratory parameters that help to
      identify children with DF or DHF.

PMID- 9237696
TI  - Dengue in the early febrile phase: viremia and antibody responses.
AB  - A multicenter effort was begun in 1994 to characterize the pathophysiology of
      dengue using a study design that minimized patient selection bias by offering
      enrollment to all children with undifferentiated fever for <72 h. In the first
      year, 189 children were enrolled (age range, 8 months to 14 years). Thirty-two
      percent of these children had dengue infections (60 volunteers). The percentage
      of children with a secondary dengue infection was 93%, with only 4 (7%) having a
      primary dengue infection. The virus isolation rate from the plasma of children
      with dengue was 98%. Viremia correlated highly with temperature. All four dengue
      virus serotypes were isolated at both study sites. This study demonstrates that
      all four serotypes of dengue virus can cause dengue hemorrhagic fever, that all
      dengue patients as defined by serology experience viremia during the febrile
      phase, and that as fever subsides, so does viremia.

PMID- 9237697
TI  - Efficacy of a recombinant glycoprotein D subunit vaccine on the development of
      primary and recurrent ocular infection with herpes simplex virus type 1 in mice.
AB  - The protective efficacy of a glycoprotein D subunit vaccine (gD2 SB AS4) was
      evaluated in a mouse model of human recurrent herpetic stromal keratitis (HSK).
      When administered before primary infection, gD2 SB AS4 protected mice against
      corneal pathology, mortality, and latency resulting from ocular viral challenge
      with herpes simplex virus type 1 (HSV-1) McKrae strain. In addition, gD2 SB AS4
      significantly decreased postreactivation corneal disease. A control vaccine, gD2
      alum, protected against acute ocular infection only. When administered after
      primary infection, gD2 SB AS4 vaccination decreased postreactivation ocular
      shedding but had no other significant effects. Vaccination with gD2 SB AS4 was
      associated with high anti-gD antibody responses and low delayed-type
      hypersensitivity responses. These results have identified a prophylactic vaccine,
      gD2 SB AS4, with activity against acute and recurrent HSK in mice and emphasize
      the need for vaccine evaluation in both primary and recurrent ocular herpetic
      disease models.

PMID- 9237698
TI  - Neutralization of cytomegalovirus virions: the role of complement.
AB  - Complement provides a key immunologic defense against invading pathogens; thus, a
      clear understanding of the interactions between cytomegalovirus (CMV) and
      complement may permit the development of strategies to enhance CMV
      neutralization. In the presence of specific anti-CMV antibodies, complement
      enhanced the neutralizing ability of serum by 2- to 3-fold. However, in the
      absence of specific anti-CMV antibodies, complement was ineffective in
      neutralizing CMV virions by plaque assay. Although complement alone did not
      mediate any neutralizing effect, CMV consumed complement activity from
      seronegative serum, resulting in the deposition of C3 on the virion. However,
      only in the presence of specific anti-CMV antibody did complement activation
      continue to the deposition of C9 on the virions. These results strongly suggest
      complement regulation by CMV virions that is modulated by anti-CMV antibody; this
      regulation may be attributed to three host complement regulators on the virions:
      CD55, CD46, and CD59.

PMID- 9237699
TI  - Diagnosis of cytomegalovirus (CMV) polyradiculopathy and documentation of in vivo
      anti-CMV activity in cerebrospinal fluid by using branched DNA signal
      amplification and antigen assays.
AB  - Branched chain DNA assay (bDNA), cytomegalovirus (CMV) antigen assay, and
      cerebrospinal fluid (CSF) viral culture were studied for their utility in the
      diagnosis of CMV polyradiculopathy and for documenting in vivo antiviral effects.
      CMV was demonstrated in 15 of 16 patients by bDNA assay, 15 of 16 by CMV antigen
      assay, and 11 of 15 by CSF culture. When clinical criteria and results of the
      other two assays were used as reference standards, the sensitivity of bDNA was
      94% and 100% and the specificity 95.2% and 100%; the CMV antigen assay
      sensitivity was 94% and 100% and specificity was 85.7% and 100%. Nine (90%) of 10
      patients with polyradiculopathy and follow-up CSF culture showed a drop in CMV
      DNA after treatment; however, only 2 (20%) improved clinically. These results
      suggest that bDNA and antigen assays may be useful methods for the diagnosis of
      CMV polyradiculopathy, but treatment failures may not be due to inadequate
      antiviral activity.

PMID- 9237700
TI  - Prevalence of penile human papillomavirus DNA in husbands of women with and
      without cervical neoplasia: a study in Spain and Colombia.
AB  - To investigate the role of men in cervical cancer, 816 husbands of women enrolled
      in four case-control studies of cervical neoplasia in populations at high
      (Colombia) and low (Spain) risk for cervical cancer were interviewed. Exfoliated
      cells from the penis were obtained and analyzed by polymerase chain reaction for
      the presence of human papillomavirus (HPV) DNA. Penile HPV DNA prevalences were
      higher in husbands of women with cervical neoplasia than in husbands of controls.
      Husbands of controls in Colombia had a 5-fold higher penile HPV DNA prevalence
      than the corresponding husbands in Spain. Strong dose-response relationships were
      found between penile HPV DNA prevalence and all sexual behavior-related variables
      in Spain but not in Colombia. Sexual promiscuity is the most important risk
      factor for penile HPV infections. Differences in HPV DNA prevalence in the male
      populations of Spain and Colombia are consistent with their 8-fold difference in
      cervical cancer incidences.

PMID- 9237701
TI  - Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in
      macaques: determinants of high virus loads and CD4 cell killing.
AB  - Chimeric simian-human immunodeficiency viruses (SHIVs) carrying envelope
      glycoproteins derived from a T cell-macrophage dual-tropic primary isolate (human
      immunodeficiency virus type 1 [HIV-1] strain DH12) were constructed. When
      inoculated into macaque monkeys, SHIV(MD14) carrying simian immunodeficiency
      virus-derived nef established significantly higher virus loads than did
      SHIV(MD1), which contains the HIV-1 nef gene. Three patterns of CD4 cell
      depletion were observed in infected monkeys: exponential and irreversible loss to
      undetectable levels within 10 weeks of infection; marked reduction during acute
      infection followed by partial recovery and stabilization (lasting from 10 weeks
      to > 1 year), with a later decline to undetectable levels in some animals; and a
      transient loss during acute infection. The induced immunodeficiency was
      accompanied by CD4 cell counts of < 50 cells/microL and was associated with
      Pneumocystis carinii pneumonia, cytomegalovirus meningoencephalitis, lymphoid
      depletion, and thymic atrophy.

PMID- 9237702
TI  - Cyclosporin A modulation of early virologic and immunologic events during primary
      simian immunodeficiency virus infection in rhesus monkeys.
AB  - Virologic and immunologic effects of immunomodulation during primary simian
      immunodeficiency virus (SIV) infection were examined in monkeys treated with
      cyclosporin or vehicle for 32 days beginning 5 days before SIV inoculation.
      Duration of antigenemia decreased in 5 of 7 treated monkeys, 2 having delayed
      onset and peak of antigenemia. Although proviral DNA levels in blood and lymph
      nodes and infected cell numbers in lymph nodes were transiently decreased, levels
      were similar to those in controls by day 14. The CD4:CD8 ratio and percentage of
      CD4+ CD29+ cells decreased in controls 14 days after inoculation, but this
      decrease was delayed in treated monkeys. Two treated monkeys demonstrated rapid
      disease, with progressive antigenemia preceding early deaths 90-96 days after
      inoculation. Nevertheless, immunomodulation influenced the kinetics of primary
      SIV infection in some monkeys, supporting the rationale of careful exploration of
      the strategy of interference with the heightened state of cellular activation
      together with direct antiretroviral therapy in human immunodeficiency virus
      infection.

PMID- 9237703
TI  - Genetic and immunologic characterization of viruses infecting MN-rgp120
      vaccinated volunteers.
AB  - Proviral sequences were determined and immunologic characterization was carried
      out for envelope glycoproteins from 7 vaccinees who became infected with human
      immunodeficiency virus type 1 (HIV-1), through high-risk behavior, while
      participating in clinical trials of MN-rgp120, a candidate HIV-1 vaccine. All 7
      infections resulted from subtype B viruses; however, only 3 of the viruses
      possessed the MN serotype-defining V3 domain sequence, IGPGRAF, prevalent in 60%
      70% of US infections. Six of the 7 viruses differed from MN-rgp120 at a
      neutralizing epitope in the C4 domain, and all 7 differed from MN-rgp120 at a
      neutralizing epitope in the V2 domain. Recombinant gp120 was prepared from each
      breakthrough specimen and tested for binding to a panel of neutralizing
      monoclonal antibodies. The results suggest that 6 of 7 breakthrough infections
      may be related to incomplete immunization or to infection with viruses that
      differed from the vaccine immunogen at important virus-neutralizing epitopes.

PMID- 9237704
TI  - Lamivudine-resistant human immunodeficiency virus type 1 variants (184V) require
      multiple amino acid changes to become co-resistant to zidovudine in vivo.
AB  - Exposure of human immunodeficiency virus to the nucleoside analogue lamivudine
      (3TC) rapidly selects for resistant variants with a valine at codon 184 (M184V)
      in the catalytic site of reverse transcriptase. In vitro, 184V demonstrated
      increased enzyme fidelity and suppressed zidovudine resistance. Clinical trials
      demonstrated that 3TC-zidovudine combination therapy results in a strong and
      sustained antiviral response. To investigate the role of 184V on in vivo virus
      evolution, the effect of zidovudine addition in 3TC-pretreated patients harboring
      184V was studied. In vivo, no significant change in fidelity was observed with
      184V, shown by generation of the classical pattern of zidovudine mutations. Of
      interest, in contrast to zidovudine monotherapy, in which just one substitution
      is sufficient for in vivo development of significant zidovudine resistance,
      multiple substitutions are required for the same level of zidovudine resistance
      in strains harboring 184V. This need for multiple substitutions may be one of the
      mechanisms explaining the sustained antiretroviral response of the 3TC-zidovudine
      combination.

PMID- 9237705
TI  - Anti-human immunodeficiency virus (HIV) activity, safety, and pharmacokinetics of
      adefovir dipivoxil (9-[2-(bis-pivaloyloxymethyl)-phosphonylmethoxyethyl]adenine)
      in HIV-infected patients.
AB  - A randomized, double-blind, placebo-controlled, dose-escalation study of adefovir
      dipivoxil, an oral prodrug of adefovir, was conducted in 36 human
      immunodeficiency virus (HIV)-infected subjects to evaluate its anti-HIV activity,
      safety, and pharmacokinetics. Subjects received placebo or one of three dosages
      of adefovir dipivoxil daily for 14 days. Median decreases in serum p24 antigen of
      31% (P = .02), 25% (P = .31), and 30% (P = .01) occurred in each drug-treated
      group, respectively, compared with an increase of 17% in the placebo group.
      Median decreases in serum HIV RNA of 0.4-0.6 log10 copies/mL occurred in the drug
      treated groups (P = .03), compared with no change in the placebo group.
      Gastrointestinal complaints and reversible liver transaminase elevations were the
      most frequently noted adverse events. Decreases in serum free carnitine occurred
      in each drug-treated group during treatment. After 14 days of dosing, adefovir
      dipivoxil demonstrated anti-HIV activity and was best tolerated at the lowest
      dosage studied, 125 mg daily.

PMID- 9237706
TI  - Increased vertical transmission of human immunodeficiency virus from hepatitis C
      virus-coinfected mothers. Women and Infants Transmission Study.
AB  - To determine if hepatitis C virus (HCV) infection affects vertical transmission
      of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the
      prospective, multicenter, Women and Infants Transmission Study had HCV antibody
      (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase
      chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV
      positive. HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%)
      versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a
      logistic regression model that included maternal drug use, a potential
      confounder, HCV infection was marginally associated with perinatal HIV
      transmission (OR, 1.64; P = .05), whereas drug use was not. Women who transmitted
      HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did
      not (337,561 copies/mL; P = .01). Maternal HCV infection is associated with
      increased HIV vertical transmission. Further studies are needed to ascertain if
      HCV directly affects perinatal HIV transmission or is a marker for another
      factor, such as maternal drug use.

PMID- 9237707
TI  - Effect of interferon-alpha and ribavirin therapy on serum GB virus C/hepatitis G
      virus (GBV-C/HGV) RNA levels in patients chronically infected with hepatitis C
      virus and GBV-C/HGV.
AB  - GB virus C/hepatitis G virus (GBV-C/HGV) is a newly described virus associated
      with hepatitis in humans, and GBV-C/HGV coinfection is common in patients
      chronically infected with hepatitis C virus (HCV). To determine the clinical
      impact of GBV-C/HGV infection in such patients and the effect of interferon-alpha
      and ribavirin therapy on serum GBV-C/HGV RNA levels, GBV-C/HGV RNA was detected
      and quantitated in serum samples from 62 chronically infected HCV patients by a
      combination of a qualitative nested reverse transcription-polymerase chain
      reaction and a newly developed quantitative branched DNA assay: 10 patients were
      positive for serum GBV-C/HGV RNA. There were no differences in the clinical,
      biochemical, and histologic features of the patients with GBV-C/HGV-HCV
      coinfection compared with those with HCV infection alone. Interferon-alpha
      treatment caused a marked but usually transient reduction in serum GBV-C/HGV RNA,
      and ribavirin had, at most, a modest antiviral effect.

PMID- 9237708
TI  - Detection of hepatitis B surface gene mutation in carrier children with or
      without immunoprophylaxis at birth.
AB  - To investigate the clinical significance of mutation in hepatitis B virus (HBV)
      surface gene, DNA sequence analysis of the "a" determinant was performed on sera
      from 27 carrier children with immunoprophylaxis, their mothers, and 21 carriers
      without vaccination. A precore mutant (G to A) at nucleotide 1896 was detected in
      sera from 11 carriers without vaccination. Mutations in the "a" determinant were
      detected in 6 (22%) of the vaccinated children. Four HBV strains showed a Gly-to
      Arg mutation at the 145th codon of the surface gene. Amino acid substitutions at
      amino acid 133 and 144 were noted in the other 2 children. Only 1 mother had the
      same predominant strain of mutant virus as her child. These observations indicate
      that immune pressure exerted by immunoprophylaxis at birth may select for a
      mutant virus.

PMID- 9237709
TI  - Regulation of Staphylococcus aureus capsular polysaccharide type 5: CO2
      inhibition in vitro and in vivo.
AB  - Staphylococcus aureus capsular polysaccharide type 5 (CP5) expression was
      investigated in lung tissue and nasal polyps of two cystic fibrosis (CF)
      patients, in rats, and in vitro using ELISA and IFA. In CF tissues, S. aureus
      expressed protein A and teichoic acid but only 1%-5% of cells expressed CP5. When
      rats were challenged with CP5-positive S. aureus in the granuloma pouch model,
      only 1%-5% of CP5-positive cells were detectable in pouch exudates. CF and pouch
      isolates, however, reexpressed CP5 (70%-90% of cells) when grown in vitro with
      air. Addition of > or = 1% CO2 to air or to O2/N2 gas mixtures reduced CP5
      expression significantly (P < .001) in a dose-dependent manner (6%-1% CP5
      positive cells). The results show that S. aureus does not produce CP5 in CF
      airways and in rat granuloma pouches and that CO2 is an environmental signal that
      regulates CP5 expression.

PMID- 9237710
TI  - Interleukin-6 gene-deficient mice show impaired defense against pneumococcal
      pneumonia.
AB  - Induction of pneumonia in C57Bl/6 mice by intranasal inoculation with 10(6) cfu
      of Streptococcus pneumoniae resulted in sustained expression of interleukin (IL)
      6 mRNA in lungs and increases in lung and plasma IL-6 concentrations. In IL-6
      deficient (IL-6-/-) mice, pneumonia was associated with higher lung levels of the
      proinflammatory cytokines tumor necrosis factor-alpha, IL-1beta, and interferon
      gamma and of the antiinflammatory cytokine IL-10 than in wild type (IL-6+/+) mice
      (all P < .05). Also, the plasma concentrations of soluble tumor necrosis factor
      receptors were higher in IL-6-/- mice (P < .05), while the acute-phase protein
      response was strongly attenuated (P < .01). Lungs harvested from IL-6-/- mice 40
      h after inoculation contained more S. pneumoniae colonies (P < .05). IL-6-/- mice
      died significantly earlier from pneumococcal pneumonia than did IL-6+/+ mice (P <
      .05). During pneumococcal pneumonia, IL-6 down-regulates the activation of the
      cytokine network in the lung and contributes to host defense.

PMID- 9237711
TI  - Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size
      on immunogenicity and interactions with simultaneously administered vaccines.
AB  - Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among
      400 infants. The vaccines differed in saccharide chain length (oligosaccharide
      [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg).
      Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls)
      for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and
      elicited mean antibody concentrations that exceeded those in controls for all 5
      capsular serotypes. PS formulations were generally more immunogenic than their OS
      counterparts. For PS vaccines, a dose-response was documented (5 microg > 2
      microg > 0.5 microg), but the differences between the 5- and 2-microg
      formulations were insignificant. The mean anti-PRP antibody concentration was
      significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines
      are more immunogenic than OS vaccines. The improved immunogenicity from
      Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn
      CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit
      protection.

PMID- 9237712
TI  - Effectiveness of the pertussis vaccination program as determined by use of the
      screening method: United States, 1992-1994.
AB  - The screening method was used to evaluate the effectiveness of the pertussis
      vaccination program in the United States during 1992-1994. The formula VE = 1 -
      [PCV/(1 - PCV)][(1 - PPV)/PPV] was used (VE = vaccine effectiveness; PCV =
      proportion of cases vaccinated; PPV = proportion of population vaccinated). Data
      from the national Supplementary Pertussis Surveillance System and the National
      Health Interview Survey were used to determine PCV and PPV, respectively. Among
      children aged 7-18 months, VE for 3 doses of pertussis vaccine was 79% (95%
      confidence interval, 74%-83%) for preventing culture-confirmed pertussis. Between
      the ages of 19 and 47 months, VE for > or = 4 doses was 90% (95% confidence
      interval, 88%-92%). VE estimates appeared lower in epidemic (1993) than non
      epidemic years (1992, 1994). VE estimates determined using the screening method
      were consistent with the previous estimates from the United States. This method
      will continue to be useful for assessing the effectiveness of the pertussis
      vaccination program in the United States, where acellular pertussis vaccines are
      recommended for infants.

PMID- 9237713
TI  - Urovirulence determinants in Escherichia coli strains causing prostatitis.
AB  - To define the urovirulence properties of Escherichia coli strains producing
      prostatitis, E. coli strains isolated from men with acute (7 strains) or chronic
      (23) prostatitis were compared with E. coli isolates from women with
      pyelonephritis (30), acute cystitis (60), or complicated urinary tract infection
      (UTI; 30). Strains from prostatitis patients were significantly more likely to
      express hemolysin than were strains causing complicated UTI (73% vs. 43%; P =
      .02) and more often demonstrated hybridization with the cytotoxic necrotizing
      factor-1 (CNF-1) probe (63%) than did strains from women (44%-48%). P fimbrial
      expression was highest among pyelonephritis (73%) and prostatitis strains (53%)
      and lowest among E. coli from women with complicated UTI (23%) and cystitis (30%;
      P < .05, prostatitis strains vs. either of the latter 2 groups). Results suggest
      that E. coli strains producing prostatitis generally possess urovirulence
      profiles similar to those of strains from women with acute uncomplicated
      pyelonephritis and that hemolysin and CNF-1 are especially prevalent in
      prostatitis strains.

PMID- 9237714
TI  - Borrelia burgdorferi adherence and injury to undifferentiated and differentiated
      neural cells in vitro.
AB  - The role of outer surface proteins (Osp) A and B and length of time in culture on
      the adhesion and cytotoxicity of Borrelia burgdorferi to C6 glioma and PC-12
      pheochromocytoma cells was investigated using 6 different spirochete strains in
      an ELISA. Statistically significant differences in adhesion between OspB mutants
      and parental isolates were not seen, yet clear differences in adhesion were noted
      between low- and high-passage isolates. Polar adhesion and penetration by the
      tips of spirochetes resulted in the formation of surface cavities and blebs.
      Adhesion of spirochetes to C6 and to undifferentiated PC-12 cells did not result
      in significant cytotoxicity, but adhesion of spirochetes to PC-12 cells
      differentiated with nerve growth factor resulted in a loss of confluence of the
      monolayer and cytotoxicity at high spirochete-to-cell ratios. These results
      demonstrate that B. burgdorferi can induce damage to neural cells directly.

PMID- 9237715
TI  - Widespread dissemination of a drug-susceptible strain of Mycobacterium
      tuberculosis.
AB  - In New York City, a large proportion of new tuberculosis cases has been caused by
      1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis.
      Between 1991 and 1994, among >600 tuberculosis patients consecutively identified
      in four large hospitals in the city, 54 with C strain, 69 with non-C cluster
      pattern strains, and 42 with noncluster pattern strains were studied.
      Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was
      compared. In a case-control analysis, 51% of patients with C strain, 28% with non
      C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found
      to be injection drug users. C strain but not 13 other unrelated isolates were
      resistant to RNI. Injection drug use may provide a selective pressure for an RNI
      resistant tubercle bacillus to emerge, which may give the organism a biologic
      advantage and explain the widespread dissemination of C strain M. tuberculosis
      within the city.

PMID- 9237716
TI  - Induction of human immunodeficiency virus type 1 expression in monocytic cells by
      Cryptococcus neoformans and Candida albicans.
AB  - Because candidiasis and cryptococcosis are common in human immunodeficiency virus
      (HIV)-infected persons, the effect of Cryptococcus neoformans and Candida
      albicans on HIV expression in monocytic cells was examined. Stimulation of the
      latently HIV-infected myelomonocytic cell line OM-10.1 with C. neoformans and C.
      albicans in the presence of pooled human serum caused a ratio-dependent increase
      in HIV production. Induction of HIV by C. neoformans was enhanced by anti
      capsular antibody, while induction by both organisms was inhibited by anti-TNF
      alpha antibody. In THP-1 cells transfected with HIV plasmid constructs, both
      organisms induced transcription from the HIV long terminal repeat that was
      dependent on intact NF-kappaB binding sequences. Thus, C. neoformans and C.
      albicans enhance HIV expression in monocytic cells through a TNF-alpha- and NF
      kappaB-dependent mechanism. In HIV-infected patients, such enhancement may
      further impair host immunity and could accelerate the course of HIV disease.

PMID- 9237717
TI  - Human immunodeficiency virus type 1 gp41 binds to Candida albicans via complement
      C3-like regions.
AB  - Oral candidiasis in human immunodeficiency virus type 1 (HIV-1)-infected persons
      is believed to be caused by the acquired T lymphocyte immunodeficiency. The
      direct interaction of C. albicans and HIV-1 in vitro was investigated. Twice as
      many yeasts adhered to cells transfected with the HIV-1 env gene as they did to
      controls. HIV-1 rsgp160 and rsgp41 but not rsgp120 were found to bind to Candida
      albicans via two C3-like regions within gp41. Normal human serum, but not C3
      depleted serum, was able to inhibit rsgp41 binding to C. albicans. Vice versa,
      rsgp160 and rsgp41 were able to block rosetting of C. albicans with iC3b-coated
      sheep erythrocytes. Binding to C. albicans, and its inhibition by rsgp41 or
      rsgp160, was confirmed for the whole virus. Therefore, oral candidiasis in HIV-1
      infected subjects may be augmented or may even be initiated by direct interaction
      between C. albicans and HIV-1 or HIV-1-infected cells.

PMID- 9237718
TI  - Outbreak of sporotrichosis among tree nursery workers.
AB  - In spring 1994, an outbreak of sporotrichosis occurred at a tree nursery in
      Florida; 9 (14%) of 65 workers involved in production of sphagnum moss topiaries
      developed lymphocutaneous sporotrichosis. A cohort study of all 65 employees was
      conducted to identify risk factors for sporotrichosis, and an environmental
      investigation was done. The risk of sporotrichosis increased significantly with
      the duration of working with sphagnum moss (P < .05), in particular with filling
      topiaries (P < .05), and with having less gardening experience (P < .05). Wearing
      gloves was protective (P < .005). Sporothrix schenckii was cultured from patients
      and sphagnum moss used in topiary production. Use of restriction fragment length
      polymorphism revealed an identical pattern for patient isolates that was
      different from the patterns of environmental isolates. Physicians should be aware
      of sporotrichosis in patients with ulcerative skin lesions who have a history of
      occupational or recreational exposure to sphagnum moss.

PMID- 9237719
TI  - Demographic, ethnic, and geographic differences between human T cell lymphotropic
      virus (HTLV) type I-seropositive carriers and persons with HTLV-I Gag
      indeterminate Western blots in Central Africa.
AB  - Using stringent Western blot (WB) criteria, human T cell lymphotropic virus
      (HTLV) type I seroprevalence among 3783 persons from representative rural
      populations of Cameroon averaged 1.1% and was higher in females (1.5%) and in
      Pygmies (2.0%), increasing with age. Furthermore, an HTLV-I Gag-indeterminate WB
      profile (HGIP), exhibiting strong reactivities to p19, p26, p28, p32, p36, and pr
      53 but lacking both p24 and env reactivity, was observed in 1.6% of the same
      populations. The prevalence of the HGIP was similar between males and females,
      did not increase with age, and appeared to cluster in tropical forests of
      southern Cameroon, especially among Pygmies (reaching 4%). These contrasting
      epidemiologic features, together with the lack of detection by polymerase chain
      reaction of HTLV-I sequences in the peripheral blood mononuclear cells of the
      persons with HGIP, strongly suggest that such a WB profile does not appear to
      reflect an HTLV-I-related viral infection but possibly an environmental (viral or
      parasitic) factor endemic in tropical rain forest areas.

PMID- 9237720
TI  - Sequential versus simultaneous combination antiretroviral regimens for the
      treatment of human immunodeficiency virus type 1 infection in vitro.
AB  - Two-, three-, and four-drug antiretroviral combinations in either simultaneous or
      sequential regimens were evaluated for their ability to suppress human
      immunodeficiency virus (HIV) type 1 replication in vitro. Zidovudine, lamivudine,
      saquinavir, and nevirapine were used at IC(90)s, IC(99)s, or IC(> or = 99)s in a
      CD4-positive human lymphoblastoid cell line (H9 cells) acutely infected with HIV
      1. In sequential regimens, drugs were added at weekly intervals. In simultaneous
      regimens, all drugs were added on day 0. Increasing the number of drugs in a
      combination regimen both increased the degree of viral inhibition and delayed the
      time of breakthrough viral replication. Simultaneous regimens provided more
      profound and earlier viral inhibition than did sequential regimens. However,
      sequential addition provided relatively more durable viral inhibition than did
      simultaneous regimens when drug concentrations were low. The relative
      effectiveness of different HIV-1 therapeutic strategies depends on both the
      numbers and concentrations of the drugs used.

PMID- 9237721
TI  - Variance of plasma human immunodeficiency virus type 1 RNA levels measured by
      branched DNA within and between days.
AB  - Previous studies have shown that CD4-positive T cells vary in a predictable
      manner over 24 h. This diurnal variance has significant clinical implications.
      Recently, viral RNA measurements have been increasingly used as a standard marker
      in the management of human immunodeficiency virus (HIV)-infected patients. Little
      detailed analysis of the variability of this marker has been conducted. To define
      the variance of plasma HIV-1 RNA levels within days, 11 clinically stable
      patients with established HIV infection and a baseline viral RNA level >40,000
      copies/mL were studied. Following the patients' admission to an inpatient
      research unit, plasma samples were obtained frequently over 48 h and analyzed for
      HIV-1 RNA levels by use of a quantitative branched chain DNA assay (bDNA). No
      diurnal pattern was detected. In these clinically stable patients, viral RNA
      levels exhibited a variance of approximately 0.4 log.

PMID- 9237722
TI  - Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for
      exposure to HCV in HCV-seronegative spouses of HCV-infected patients.
AB  - Lymphocyte reactivity against hepatitis C virus (HCV) antigens was studied in 20
      couples in which 1 member had chronic hepatitis C. This was done to investigate
      the possibility of HCV transmission between spouses that was not followed by
      seroconversion. Twenty healthy subjects without any risk factors for HCV
      transmission served as negative controls. All the patients' spouses and the
      healthy controls were negative for HCV RNA and for anti-HCV antibody. Lymphocytes
      were cultured with recombinant HCV core and nonstructural antigens (c22, c33,
      c100, c200, and NS5) and with control antigens (sperm whale myoglobin, chicken
      lysozyme, and superoxide dismutase). Lymphocytes from 10 patients and 4
      seronegative spouses proliferated in the presence of at least one HCV antigen. No
      proliferation was shown with nonspecific antigens or in the control group. This
      study gives evidence for possible in vivo priming with HCV antigens that did not
      lead to seroconversion in spouses of HCV-positive patients.

PMID- 9237723
TI  - Surface expression of intercellular adhesion molecule 1 on epithelial cells in
      the human adenoid.
AB  - Human rhinoviruses enter the host by way of the nose and conjunctiva.
      Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the
      majority of rhinoviruses. ICAM-1 expression on the luminal surface of epithelial
      cells in the upper airway may be an important determinant of virus localization
      in the airway. Eighteen adenoids and 5 nasopharyngeal biopsies were evaluated by
      immunohistochemistry for surface expression of ICAM-1. Heavy immunoreactivity of
      ICAM-1 was found on the surface of a small number of single nonciliated cells in
      the lymphoepithelium. Squamous epithelial cells showed minimal to no staining,
      and ciliated epithelium had positive ICAM-1 staining of the basal cells but not
      on the ciliated border. The localization of ICAM-1 expression to specific,
      limited areas of the surface epithelium of the nasopharynx may have important
      implications in the pathogenesis of rhinovirus infections, especially initiation
      of the host response to rhinovirus.

PMID- 9237724
TI  - A new multiantigen immunoassay for the quantification of IgG antibodies to
      capsular polysaccharides of Streptococcus pneumoniae.
AB  - A new nitrocellulose-based solid-phase multiantigen immunoassay (MAIA) for the
      detection of serum antibodies to Streptococcus pneumoniae capsular
      polysaccharides (PPSs) is presented. Evaluation with human sera showed that the
      MAIA test is reproducible, sensitive, and specific. It correlated well with a
      conventional ELISA method. The multiantigen strip system allowed quantification
      of antibodies against several PPS serotypes simultaneously and with a minimal
      amount of serum specimen. The presented solid-phase immunoassay for the
      quantification of anti-PPS antibodies seems to be a superior and attractive
      alternative to currently used ELISA tests and offers possibilities for
      standardization.

PMID- 9237725
TI  - Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous
      leprosy.
AB  - Genetically determined differences in immune responses to environmental agents
      may underlie susceptibility to many autoimmune and infectious diseases. Leprosy
      provides an example of a polarity in the type of immune response made to an
      infectious agent, and there is evidence that the major histocompatibility complex
      is genetically linked to leprosy type. It was found that HLA-DR2 is associated
      with both tuberculoid and lepromatous types of leprosy; however, a variant at
      position -308 of the promoter of the neighboring tumor necrosis factor (TNF) gene
      was increased in frequency in lepromatous (odds ratio = 3.0, P = .02) but not
      tuberculoid leprosy. Some studies have found higher serum levels of TNF in
      lepromatous than tuberculoid leprosy, and high TNF levels are found in malaria
      and leishmaniasis, which are also associated with this TNF allele. It is
      speculated that this association reflects genetic variability in cytokine
      production, which influences the immune response to and clinical outcome of
      leprosy.

PMID- 9237726
TI  - Detection of rifampin resistance in Mycobacterium tuberculosis by use of a rapid,
      simple, and specific RNA/RNA mismatch assay.
AB  - An adaption of an RNA/RNA duplex, base pair-mismatch assay is capable of
      detecting rifampin resistance in Mycobacterium tuberculosis. The specificity and
      sensitivity of the mismatch assay in detecting rifampin resistance were 100% and
      96%, respectively, when tested against 46 rifampin-resistant and rifampin
      susceptible strains of M. tuberculosis. By use of a range of mycobacterial and
      nonmycobacterial prokaryote pathogens, the mismatch assay was shown to be
      specific for M. tuberculosis and Mycobacterium bovis. The assay is cost-effective
      compared with DNA sequencing and other molecular methods and is simple to perform
      and interpret. Furthermore, the assay can return a result within 24 h after
      receipt of an isolated organism and potentially can be used directly with smear
      positive specimens.

PMID- 9237727
TI  - Mechanisms of impaired anticryptococcal activity of monocytes from donors
      infected with human immunodeficiency virus.
AB  - The mechanisms by which monocytes from patients infected with human
      immunodeficiency virus (HIV) have reduced growth inhibitory activity against
      Cryptococcus neoformans was examined. Monocyte-enriched peripheral blood
      mononuclear cells from 12 HIV-seropositive donors with CD4 cell counts of 10-210
      cells/mm3 (median, 85) and HIV-seronegative donors were compared in assays to
      determine the binding and phagocytosis of C. neoformans and the respiratory burst
      and degranulation in response to C. neoformans and zymosan. Monocytes from HIV
      infected and uninfected persons bound and ingested C. neoformans equally well;
      however, generation of hydrogen peroxide and specific release of beta
      glucuronidase in response to C. neoformans was significantly reduced in monocyte
      enriched cells from the HIV-infected donors. The impaired anticryptococcal
      activity of monocytes from persons with HIV may be related to defects in both
      oxidative and nonoxidative effector pathways that occur after the binding and
      internalization of the organism.

PMID- 9237728
TI  - Human herpesvirus 8 DNA sequences in CD8+ T cells.

PMID- 9237729
TI  - Hepatitis C virus infection in a human immunodeficiency virus-positive cohort in
      Hawaii.

PMID- 9237730
TI  - Coinfection with human T lymphotropic virus type I and human immunodeficiency
      virus.

PMID- 9237731
TI  - Polio vaccines and retroviral contamination.

PMID- 9237732
TI  - Progress on patents, but more action is needed.

PMID- 9237733
TI  - Planting a sound idea.

PMID- 9237734
TI  - Pressure grows for inquiry into welfare of transgenic animals.

PMID- 9237735
TI  - NSF urged to increase plant genome sequencing effort.

PMID- 9237736
TI  - Call for human subjects monitoring body.

PMID- 9237737
TI  - Collins' student sanctioned over 'most severe' case of fraud.

PMID- 9237739
TI  - Swiss researchers facing 'anti-transgenics' vote.

PMID- 9237740
TI  - NIH and genome project set for more funds.

PMID- 9237738
TI  - Euro-vote lifts block on biotech patents...but parliament wants closer scrutiny.

PMID- 9237741
TI  - Talks start on policing bio-weapons ban...as 'designer weapons' threat is
      disputed.

PMID- 9237742
TI  - The serious business of listing authors.

PMID- 9237744
TI  - Salmonella or Smithella?

PMID- 9237743
TI  - Cloning, dignity and ethical revisionism.

PMID- 9237745
TI  - Fat rats and carcinogenesis screening.

PMID- 9237746
TI  - Seeking wisdom in innate immunity.

PMID- 9237747
TI  - Palaeoanthropology. Fossil muzzles and other puzzles.

PMID- 9237748
TI  - Protein folding. The difference with prokaryotes.

PMID- 9237749
TI  - A new west African chimpanzee subspecies?

PMID- 9237750
TI  - Imaging individual green fluorescent proteins.

PMID- 9237751
TI  - Recombination of protein domains facilitated by co-translational folding in
      eukaryotes.
AB  - The evolution of complex genomes requires that new combinations of pre-existing
      protein domains successfully fold into modular polypeptides. During eukaryotic
      translation model two-domain polypeptides fold efficiently by sequential and co
      translational folding of their domains. In contrast, folding of the same proteins
      in Escherichia coli is posttranslational, and leads to intramolecular misfolding
      of concurrently folding domains. Sequential domain folding in eukaryotes may have
      been critical in the evolution of modular polypeptides, by increasing the
      probability that random gene-fusion events resulted in immediately foldable
      protein structures.

PMID- 9237752
TI  - On/off blinking and switching behaviour of single molecules of green fluorescent
      protein.
AB  - Optical studies of individual molecules at low and room temperature can provide
      information about the dynamics of local environments in solids, liquids and
      biological systems unobscured by ensemble averaging. Here we present a study of
      the photophysical behaviour of single molecules of the green fluorescent protein
      (GFP) derived from the jellyfish Aequorea victoria. Wild-type GFP and its mutant
      have attracted interest as fluorescent biological labels because the fluorophore
      may be formed in vivo. GFP mutants immobilized in aereated aqueous polymer gels
      and excited by 488-nm light undergo repeated cycles of fluorescent emission
      ('blinking') on a timescale of several seconds-behaviour that would be
      unobservable in bulk studies. Eventually the individual GFP molecules reach a
      long-lasting dark state, from which they can be switched back to the original
      emissive state by irradiation at 405 nm. This suggests the possibility of using
      these GFPs as fluorescent markers for time-dependent cell processes, and as
      molecular photonic switches or optical storage elements, addressable on the
      single-molecule level.

PMID- 9237753
TI  - Earliest known Old World monkey skull.
AB  - Similarities of the skull are commonly used to support hypotheses of ancestor
      descendant relationships between fossil and living ape genera, especially between
      the late Miocene apes Sivapithecus and Dryopithecus from Eurasia and the living
      orang-utan (Pongo) from Borneo and Sumatra. Yet determining whether craniofacial
      traits shared by extant and Miocene apes are primitive or derived is severely
      hampered by the rarity of well-preserved fossil crania, particularly of early
      members of their closest outgroup, the Old World monkeys (Cercopithecoidea). The
      discovery of a complete and undistorted skull of Victoriapithecus at middle
      Miocene deposits from Maboko Island, Kenya, provides evidence of intact cranial
      vault and basicranial morphology, brain size and craniofacial hafting for a
      primate from between 32 and 7 million years ago. Victoriapithecus represents a
      branch of Old World monkey that is intermediate between extant cercopithecids
      (Colobinae and Cercopithecinae) and the common ancestor they shared with apes
      (Hominoidea). The skull preserves traits widely thought to be derived for extant
      and fossil members of a proposed Sivapithecus/Pongo clade, but which now appear
      to be primitive features of ancestral Old World higher primates in general.

PMID- 9237754
TI  - Different types of fear-conditioned behaviour mediated by separate nuclei within
      amygdala.
AB  - The amygdala has long been thought to be involved in emotional behaviour, and its
      role in anxiety and conditioned fear has been highlighted. Individual amygdaloid
      nuclei have been shown to project to various cortical and subcortical regions
      implicated in affective processing. Here we show that some of these nuclei have
      separate roles in distinct mechanisms underlying conditioned fear responses. Rats
      with lesions of the central nucleus exhibited reduction in the suppression of
      behaviour elicited by a conditioned fear stimulus, but were simultaneously able
      to direct their actions to avoid further presentations of this aversive stimulus.
      In contrast, animals with lesions of the basolateral amygdala were unable to
      avoid the conditioned aversive stimulus by their choice behaviour, but exhibited
      normal conditioned suppression to this stimulus. This double dissociation
      demonstrates that distinct neural systems involving separate amygdaloid nuclei
      mediate different types of conditioned fear behaviour. We suggest that theories
      of amygdala function should take into account the roles of discrete amygdala
      subsystems in controlling different components of integrated emotional responses.

PMID- 9237755
TI  - Infants listen for more phonetic detail in speech perception than in word
      learning tasks.
AB  - Infants aged 4-6 months discriminate the fine phonetic differences that
      distinguish syllables in both their native and unfamiliar languages, but by 10-12
      months their perceptual sensitivities are reorganized so that they discriminate
      only the phonetic variations that are used to distinguish meaning in their native
      language. It would seem, then, that infants apply their well honed phonetic
      sensitivities as they advance and begin to associate words with objects, but the
      question of how speech perception sensitivities are used in early word learning
      has not yet been answered. Here we use a recently developed technique to show
      that when they are required to pair words with objects, infants of 14 months fail
      to use the fine phonetic detail they detect in syllable discrimination tasks. In
      contrast, infants of 8 months--who are not yet readily learning words-
      successfully discriminate phonetic detail in the same task in which infants aged
      14 months fail. Taken together, these results suggest a second reorganization in
      infants's use of phonetic detail as they move from listening to syllables to
      learning words.

PMID- 9237756
TI  - Laminar fine structure of frequency organization in auditory midbrain.
AB  - The perception of sound is based on signal processing by a bank of frequency
      selective auditory filters, the so-called critical bands. Here we investigate how
      the internal frequency organization of the main auditory midbrain station, the
      central nucleus of the inferior colliculus (ICC), might contribute to the
      generation of the critical-band behaviour of its neurons. We find a unique
      spatial arrangement of the frequency distribution in the ICC that correlates with
      psychophysical critical-band characteristics. Systematic frequency
      discontinuities along the main tonotopic axis, in combination with a smooth
      frequency gradient orthogonal to the main tonotopic organization of cat ICC,
      reflect a layering of the frequency organization paralleling its anatomical
      laminae. This layered frequency organization is characterized by constant
      frequency ratios of corresponding locations on neighbouring laminae and may
      provide a spatial framework for the generation of critical bands and for signal
      processing within and across frequency bands for the analysis of sound.

PMID- 9237757
TI  - Kinesin hydrolyses one ATP per 8-nm step.
AB  - Kinesin is a two-headed, ATP-dependent motor protein that moves along
      microtubules in discrete steps of 8 nm. In vitro, single molecules produce
      processive movement; motors typically take approximately 100 steps before
      releasing from a microtubule. A central question relates to mechanochemical
      coupling in this enzyme: how many molecules of ATP are consumed per step? For the
      actomyosin system, experimental approaches to this issue have generated
      considerable controversy. Here we take advantage of the processivity of kinesin
      to determine the coupling ratio without recourse to direct measurements of ATPase
      activity, which are subject to large experimental uncertainties. Beads carrying
      single molecules of kinesin moving on microtubules were tracked with high spatial
      and temporal resolution by interferometry. Statistical analysis of the intervals
      between steps at limiting ATP, and studies of fluctuations in motor speed as a
      function of ATP concentration, allow the coupling ratio to be determined. At near
      zero load, kinesin molecules hydrolyse a single ATP molecule per 8-nm advance.
      This finding excludes various one-to-many and many-to-one coupling schemes,
      analogous to those advanced for myosin, and places severe constraints on models
      for movement.

PMID- 9237758
TI  - Coupling of kinesin steps to ATP hydrolysis.
AB  - A key goal in the study of the function of ATP-driven motor enzymes is to
      quantify the movement produced from consumption of one ATP molecule. Discrete
      displacements of the processive motor kinesin along a microtubule have been
      reported as 5 and/or 8 nm. However, analysis of nanometre-scale movements is
      hindered by superimposed brownian motion. Moreover, because kinesin is processive
      and turns over stochastically, some observed displacements must arise from
      summation of smaller movements that are too closely spaced in time to be
      resolved. To address both of these problems, we used light microscopy
      instrumentation with low positional drift (< 39 pms[-1]) to observe single
      molecules of a kinesin derivative moving slowly (approximately 2.5nm s[-1]) at
      very low (150nM) ATP concentration, so that ATP-induced displacements were widely
      spaced in time. This allowed increased time-averaging to suppress brownian noise
      (without application of external force), permitting objective measurement of the
      distribution of all observed displacement sizes. The distribution was analysed
      with a statistics-based method which explicitly takes into account the occurrence
      of unresolved movements, and determines both the underlying step size and the
      coupling of steps to ATP hydrolytic events. Our data support a fundamental
      enzymatic cycle for kinesin in which hydrolysis of a single ATP molecule is
      coupled to a step distance of the microtubule protofilament lattice spacing of
      8.12 nm. Step distances other than 8nm are excluded, as is the coupling of each
      step to two or more consecutive ATP hydrolysis reactions with similar rates, or
      the coupling of two 8-nm steps to a single hydrolysis. The measured ratio of ATP
      consumption rate to stepping rate is invariant over a wide range of ATP
      concentration, suggesting that the 1 ATP to 8nm coupling inferred from behaviour
      at low ATP can be generalized to high ATP.

PMID- 9237759
TI  - A human homologue of the Drosophila Toll protein signals activation of adaptive
      immunity.
AB  - Induction of the adaptive immune response depends on the expression of co
      stimulatory molecules and cytokines by antigen-presenting cells. The mechanisms
      that control the initial induction of these signals upon infection are poorly
      understood. It has been proposed that their expression is controlled by the non
      clonal, or innate, component of immunity that preceded in evolution the
      development of an adaptive immune system in vertebrates. We report here the
      cloning and characterization of a human homologue of the Drosophila toll protein
      (Toll) which has been shown to induce the innate immune response in adult
      Drosophila. Like Drosophila Toll, human Toll is a type I transmembrane protein
      with an extracellular domain consisting of a leucine-rich repeat (LRR) domain,
      and a cytoplasmic domain homologous to the cytoplasmic domain of the human
      interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known
      to signal through the NF-kappaB pathway. We show that a constitutively active
      mutant of human Toll transfected into human cell lines can induce the activation
      of NF-kappaB and the expression of NF-kappaB-controlled genes for the
      inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the co
      stimulatory molecule B7.1, which is required for the activation of naive T cells.

PMID- 9237760
TI  - A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR
      proteins in splicing of pre-mRNA.
AB  - Recognition of a functional 3' splice site in pre-mRNA splicing requires a
      heterodimer of the proteins U2AF65/U2AF35. U2AF65 binds to RNA at the
      polypyrimidine tract, whereas U2AF35 is thought to interact through its
      arginine/serine-rich (RS) domain with other RS-domain-containing factors bound at
      the 5' splice site, assembled in splicing enhancer complexes, or associated with
      the U4/U6.U5 small nuclear ribonucleoprotein complex. It is unclear, however, how
      such network interactions can all be established through the small RS domain in
      U2AF. Here we describe the function of a U2AF35-related protein (Urp), which is
      the human homologue of a mouse imprinted gene. Nuclear extracts depleted of Urp
      are defective in splicing, but activity can be restored by addition of
      recombinant Urp. U2AF35 could not replace Urp in complementation, indicating that
      their functions do not overlap. Co-immunodepletion showed that Urp is associated
      with the U2AF65/U2AF35 heterodimer. Binding studies revealed that Urp
      specifically interacts with U2AF65 through a U2AF35-homologous region and with SR
      proteins (a large family of RS-domain-containing proteins) through its RS domain.
      Therefore, Urp and U2AF35 may independently position RS-domain-containing factors
      within spliceosomes.

PMID- 9237761
TI  - Detection of chromosomal alterations affecting the 1cen-1q12 region in irradiated
      granulocytes and lymphocytes by multicolour FISH with tandem DNA probes.
AB  - A multicolour tandem labelling fluorescence in situ hybridization (FISH)
      procedure was used to compare the frequencies of radiation-induced chromosome
      breakage and hyperdiploidy of chromosome 1 occurring in non-cultured granulocytes
      and Go lymphocytes with those observed in cultured metaphase and interphase
      lymphocytes. Whole blood, obtained from healthy male donors, was exposed in vitro
      to 0, 100, 200, 300 and 400 cGy of ionizing radiation from a 137Cs source.
      Aliquots containing granulocytes and Go lymphocytes from each dose were treated
      immediately with hypotonic KCI on ice and harvested. Cells were hybridized with
      alpha- and classical satellite probes to the 1cen-q12 region of chromosome 1 and
      the frequencies of hyperdiploidy and breakage affecting this region were
      determined. Elevated dose-related frequencies of breakage were detectable in both
      lymphocytes and granulocytes immediately following radiation and decreased
      rapidly over the first 0.25-2 h. In a second series of experiments, the
      frequencies of hyperdiploidy and breakage for uncultured granulocytes and Go
      lymphocytes were compared with interphase and metaphase cells following 48-51 h
      of culture. Similar and significant dose-related increases in breakage were seen
      for the granulocytes, Go lymphocytes, 48 h cultured interphase and metaphase
      lymphocytes. A minor increase in hyperdiploidy was seen in the irradiated
      cultured cells, whereas no hyperdiploid cells were detected in the non-cultured
      cells. These results indicate that, in general, granulocytes and lymphocytes show
      similar sensitivity to radiation-induced damage and that cell culture is not
      required for chromosome breakage to be observed microscopically using this FISH
      procedure.

PMID- 9237762
TI  - Extruded micronuclei induced by colchicine or acrylamide contain mostly lagging
      chromosomes identified in paintbrush smears by minor and major mouse DNA probes.
AB  - In the mouse bone marrow micronucleus assay, it was studied whether micronuclei
      (MN) could be expelled from polychromatic erythrocytes (PCE) in a similar way to
      the main nucleus. To avoid the disrupting centrifugation step of the conventional
      bone marrow preparation procedure, the paintbrush technique was used in the
      present experiments. With May-Grunwald-Giemsa staining of paintbrush slides, 5 %
      of the colchicine (COL)-induced MN were found attached to the outside membranes
      of PCE and were regarded as extruded. Of the acrylamide (AA)-induced MN, 22% were
      extruded. After fluorescence in situ hybridization (FISH) of a total of 300 MN
      per chemical treatment with the mouse minor and major satellite DNA probes, 9.7%
      MN were extruded in the COL group and 8.3% MN were extruded in the AA group. FISH
      showed that 76% of the retained COL-induced MN were signal-positive, indicating
      that they contained entire chromosomes. With AA, 29% minor-positive and 28.3 %
      major-positive retained MN were found, confirming its known clastogenicity.
      However, the observed frequency of signal-positive MN (1.7 MNPCE(pos)/ 1000 PCE)
      in the AA group was about three times higher than in the control (0.5
      MNPCE(pos)/1000 PCE) which indicates that AA has aneugenic potential. FISH
      analysis of the extruded MN showed 72-100% major as well as minor signals. It is
      concluded that expelled MN contain mostly entire chromosomes.

PMID- 9237763
TI  - Evaluation of manual and image analysis quantification of DNA damage in the
      alkaline comet assay.
AB  - The alkaline comet assay or single cell microgel electrophoresis assay is a
      sensitive method of detecting DNA strand breaks and alkali labile sites in
      individual cells. The results of this assay can be analysed by different methods.
      In this study we compared analyses of the same slides by a manual method and by
      image analysis, post-treatment of clone 707 Friend erythroleukaemia cells with
      H2O2. The parameters which were found to be particularly useful were comet area
      and comet length (measured manually) and percentage tail DNA, tail moment, tail
      length and tail length/head radius (L/H), measured using image analysis. The
      manual method for comet analysis presented in this paper would appear to provide
      good and reliable comet data. However, the image analysis comet system described
      offers an alternative analysis method which avoids the need for photomicrographs
      and tedious manual analysis. The image analysis parameters: % tail DNA, tail
      moment, tail length and L/H give good consistent results and for large-scale
      analysis it will, therefore, conceivably be the method of choice.

PMID- 9237764
TI  - Aniline and its metabolites generate free radicals in yeast.
AB  - The carcinogen aniline is negative in the Ames Salmonella mutagenicity assay.
      Aniline does, however, induce intrachromosomal recombination between repeated
      sequences in Saccharomyces cerevisiae, resulting in deletion (DEL) of intervening
      sequences. We have investigated whether the generation of oxidative free radical
      species by aniline and/ or its metabolites may be responsible for its
      recombinagenic activity in yeast. The toxicity and recombinagenicity of aniline
      in yeast were greatly reduced in the presence of the free radical scavenger N
      acetyl cysteine. Aniline cytotoxicity was many-fold increased in strains of
      S.cerevisiae lacking the antioxidant enzyme superoxide dismutase. Aniline also
      induced oxidation of the intracellular free radical-sensitive reporter compound
      2,4-dichlorofluorescin diacetate to its fluorescent derivative 2,4
      dichlorofluorescein in vivo in S.cerevisiae. The aniline metabolites 4
      aminophenol and 2-aminophenol were significantly more potent inducers of DEL
      recombination in yeast than aniline. In contrast, the secondary metabolite 4
      acetamidophenol (acetaminophen) was non-toxic and non-recombinagenic in yeast. 4
      Aminophenol and 2-aminophenol were also significantly more toxic than aniline in
      a superoxide dismutase deficient yeast strain. 4-aminophenol was a significantly
      more potent oxidizer of 2,4-dichlorofluorescin diacetate than aniline. The
      Escherichia coli soxS promoter, which is induced in the presence of redox cycling
      agents like paraquat, was induced weakly by aniline at toxic doses. The soxS
      promoter was strongly induced by 4-aminophenol and 2-aminophenol. The results
      indicate a role for oxidative stress, mediated by generation of superoxide
      radical, in the toxicity and recombinagenicity of aniline. The increased activity
      of 4-aminophenol and 2-aminophenol suggests that ring hydroxylation may be an
      important activating step in this process.

PMID- 9237765
TI  - Modulation of the clastogenic activity of bleomycin by reduced-glutathione,
      glutathione-ester and buthionine sulphoximine.
AB  - In this study an attempt has been made to establish a relationship between
      bleomycin (BLM)-induced DNA damage and buthionine sulphoximine (BSO)-mediated
      modified endogenous glutathione (GSH) status in normal human lymphocytes. Present
      results demonstrate that depletion of endogenous GSH by BSO reduced the
      clastogenic action of BLM, whereas elevation of endogenous GSH by treating the
      cells with GSH and GSH-ester, potentiates the cytotoxicity of BLM. A significant
      reduction in the frequency of deletions and chromatid breaks was observed when
      BSO-treated cells were treated with BLM. Again the frequency of these two types
      of aberrations was increased significantly when GSH- and GSH-ester-treated cells
      were treated with BLM. The observed reduction in the effect of BLM in GSH
      depleted cells could be explained on the basis of the failure of reactivation of
      the oxidized BLM by reducing agent GSH which is present endogenously. Similarly,
      it appears that radicals which are generated due to reduction of oxidized BLM by
      the increased level of cellular GSH, after treating the cells with GSH or GSH
      ester, could be responsible for the increasing frequency of deletion and
      chromatid breaks.

PMID- 9237766
TI  - Comparison between micronucleated lymphocyte rates observed in healthy subjects
      and cancer patients.
AB  - Micronucleated cell rates were assessed in cytokinesis-blocked lymphocytes of 198
      male and female healthy subjects (HS) not occupationally exposed to genotoxic
      risks and of 70 male and female cancer patients (CP) prior to any anticancer
      treatment. In the HS group, spontaneous micronucleated cell rates (MN cell rates)
      were 9.7 +/- 2.8 per 1000 binucleated lymphocytes and 9.8 +/- 3.1 for males and
      females respectively. In the CP group, spontaneous MN cell rates were 21.1 +/-
      15.3 per 1000 binucleated lymphocytes and 19.1 +/- 11.2 for males and females
      respectively. Moreover, they were shown to have a large inter-individual
      variability in the two groups. The study of inter-individual variation factors
      showed that only tobacco could affect MN cell rate in HS whereas age and sex
      apparently had no significant effect. In the CP group, only age significantly
      affected MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and
      tumour stage had no significant effect. There was no significant difference in
      the distribution of gender between HS and CP, whereas there was a significant
      difference in the distribution of age and tobacco between the two groups. The
      comparison of MN cell rates in 54 HS and 54 CP matched for age and sex showed a
      statistically significant difference. Spontaneous MN cell rates of these two
      populations reflect environmental exposure. Moreover, for CP it most probably
      refers to various cellular lesions and genetic damage.

PMID- 9237767
TI  - Sister chromatid exchange (SCE) rates in human melanoma cells as an index of
      mutagenesis.
AB  - Melanomas are highly clonogenic. Genetic variability and polymorphism of tumour
      cell populations have been reported. However, no direct evidence of mutator
      activity as a source of genetic polymorphism for melanoma cells has been
      described. Some intermediates of melanin synthesis are cytotoxic and genotoxic
      and their mutagenic power has been described. We show here that the rate of
      sister chromatid exchange (SCE) of the line of human melanoma cells used varies
      with the concentration of the melanin precursor L-tyrosine, in the culture
      medium. An increase of melanin synthesis results in increased SCE rates. The
      highest values of SCEs are found in melanotic melanoma cells compared with the
      amelanotic ones. Indeed we present evidence that melanoma cells show higher
      levels of SCE when compared with normal human lymphocytes, and to the SCE
      frequencies derived from the literature on the lymphocytes of familial malignant
      melanoma, sporadic malignant melanoma patients and the lymphocytes of relatives
      of familial and sporadic melanoma patients.

PMID- 9237768
TI  - Genotoxic changes after low-level solvent and fuel exposure on aircraft
      maintenance personnel.
AB  - Individuals may be exposed to solvent mixtures and fuel either at work or home,
      through air, water and food contamination. Few studies have addressed the
      genotoxic effects of mixed, low-level exposure to fuel and solvent. This was an
      optimally designed study where each subject was sampled prior to exposure and
      after 15 and 30 weeks while exposed, in a repeated measures design with each
      subject serving as his own control. Fifty men aged between 18 and 50, working on
      aircraft equipment operation and maintenance at a military installation were
      included. Eight unexposed men were concurrently sampled. Sister-chromatid
      exchanges (SCE) and micronuclei (MN) frequency were measured in conjunction with
      air sampling and expired breath analysis for jet fuel (JP-4), 1,1,1
      trichloroethane, methyl ethyl ketone, xylenes, toluene and methylene chloride.
      Exposure levels measured by industrial hygiene were very low (all means <6
      p.p.m.), <10% of the OSHA standard. Expired breath levels were also low, <25
      p.p.b. A small but statistically significant increase in the frequency of SCE
      occurred after 30 weeks of exposure for sheet metal workers (P = 0.003) and for
      painters (P = 0.05). The MN frequency in the sheet metal workers initially showed
      a statistically significant increase, but by 30 weeks had decreased. Cigarette
      smoking, alcohol and caffeine use were not associated with changes from baseline
      for either MN or SCE. Smokers, however, had significantly higher values of SCEs
      at baseline than did nonsmokers. In summary, these findings suggest that small
      increases in SCEs in particular, may serve as a sensitive biologic indicator of
      low level hydrocarbon exposure in as much as statistically significant changes
      occurred in the highest exposed groups but not in the low or no exposure groups.
      Chance occurrence or exposures to other occupational or non-occupational agents
      cannot be eliminated as a cause of the study findings.

PMID- 9237769
TI  - Characterization of enzyme activities and cofactors involved in bioactivation and
      bioinactivation of chemical carcinogens in the tester strains Escherichia coli
      K12 MX100 and Salmonella typhimurium LT2 TA100.
AB  - MX100 is an Escherichia coli K12 genotoxicity tester strain, especially developed
      for mechanistic studies of chemical mutagens and carcinogens. For the study of
      the role of specific enzymes in the bioactivation and bioinactivation of
      carcinogens, it is necessary to characterize MX100 as far as its metabolic
      bio(in)activation capacities are concerned. In this study such a characterization
      is performed in two types of cell-free lysates, one derived from stationary phase
      cells, grown in rich medium (SR-lysates) and one from exponentially growing cells
      (log phase), cultured in minimal medium (LM-lysates). Six Phase I enzyme
      activities of aromatic NADPH hydroxylase, NADH hydroxylase, flavin-containing
      monooxygenase (FMO), nitroreductase, DT-diaphorase and NADPH
      ferredoxin:oxidoreductase were determined. Activities of six Phase II enzymes
      glutathione S-transferases (GSTs), N-aryl acetyltransferase (NAT), arylamine
      sulphotransferase, UDP-glucuronyltransferase and epoxide hydratase and of the
      Phase III enzyme cysteine conjugate beta-lyase were subsequently assessed. In
      addition, five antioxidant enzymes: superoxide dismutase (SOD), catalase,
      glutathione (GSH)-reductase, GSH-peroxidase and alkyl hydroperoxide reductase; as
      well as concentrations of glutathione (GSH) and its disulphide (GSSG), were
      measured. The activity parameters of all enzymes were compared with those
      obtained in similar lysates of the Salmonella strain TA100 and in rat liver
      preparations. The results indicate that MX100 as well as TA100 contain relatively
      low oxidative but high reductase Phase I activities. Both strains demonstrated
      low activities for the Phase II conjugation enzymes except for GSTs. In MX100,
      relatively high activities were detected for all antioxidative enzymes,
      activities which were lower in TA100. Significant differences in activities were
      observed between the SR-lysates derived from stationary phase/rich medium and LM
      lysates from log phase/minimal medium cells for nitroreductase, GST, SOD,
      catalase, NADPH ferredoxin:oxidoreductase as well as in GSH content. In general,
      we described for the first time a metabolic characterization of the E.coli tester
      strain MX100 and the Salmonella typhimurium strain TA100 and discussed the
      results in terms of its significance for carcinogen bioactivation and
      bioinactivation capacities.

PMID- 9237770
TI  - CI solvent yellow 14 shows activity in the bone marrow micronucleus assay in both
      the rat and mouse.
AB  - CI Solvent Yellow 14 has been reported to be carcinogenic in the rat, inducing
      neoplastic liver nodules, but non-carcinogenic in the mouse. The present
      experiments have extended previously reported investigations on the activity of
      CI Solvent Yellow 14 in in vivo genotoxicity assays. CI Solvent Yellow 14 has
      been examined for genotoxicity in vivo in the bone marrow micronucleus assay in
      both the rat and the mouse, and in the rat liver unscheduled DNA synthesis (DNA
      repair) assay, to limit doses of 5000 and 2000 mg/kg respectively, by oral
      gavage. CI Solvent Yellow 14 showed evidence of clastogenic activity in both the
      rat and mouse bone marrow (clear effect in the rat; weak effect in the mouse),
      but no evidence of DNA repair in the rat liver. In view of the latter finding,
      the contribution, if any, of the genotoxicity expressed by the micronucleus assay
      to the formation of liver nodules on chronic administration of the compound, is
      unclear.

PMID- 9237771
TI  - Damage proneness induced by genomic DNA demethylation in mammalian cells
      cultivated in vitro.
AB  - Variations in the genomic DNA methylation level have been shown to be an
      epigenetic inheritable modification affecting, among other targets, the sister
      chromatid exchange (SCE) rate in mammalian cells in vitro. The inheritable
      increase in SCE rate in affected cell populations appears as a puzzling
      phenomenon in view of the well established relation between SCE and both
      mutagenesis and carcinogenesis. In the present work we demonstrate that, in a
      treated cell population, demethylation could be responsible for the inheritable
      induction of damage proneness affecting both damage induction and repair. Normal
      and ethionine or azacytidine treated Chinese hamster ovary cells, subclone K1
      (CHO-K1), were challenged with UV light (UV) or mitomycin-C (MMC) at different
      times from the demethylating treatment. The SCE rate was measured with two main
      objects in view: (i) the induction of synergism or additivity in combined
      treatments, where mutagen (UV or MMC) pulse is supplied from 0 to 48 h after the
      end of the demethylating treatment; and (ii) the pattern of damage extinction,
      for the duration of up to six cell cycles after the end of the combined
      (demethylating agent + mutagen) treatment. Results indicate both a synergism in
      SCE induction by mutagens in demethylated cells even if supplied up to four cell
      cycles after the end of the demethylation treatment and a delay in recovery of
      induced damage, compared with normally methylated cells. These data are discussed
      in the light of the supposed mechanism of SCE increase and of the possible
      biological significance in terms of mutagenesis and carcinogenesis.

PMID- 9237772
TI  - Genotoxicity of tetrodotoxin from puffer fish tested in root meristem cells of
      Allium cepa L.
AB  - Tetrodotoxin (TTX) extracted and purified from puffer fish Arothron
      nigropunctatus was tested for genotoxicity employing the root meristem cells of
      Allium cepa as the assay system. The genotoxicity endpoints investigated were
      mitotic index (MI), meta-anaphases with spindle aberrations, interphases with
      micronuclei (MNC) and sister chromatid exchanges (SCE) in metaphase chromosomes.
      The results demonstrated that TTX inhibited mitosis at concentrations of > or =
      30 microM as evident by the fall of MI, but failed to induce MNC at significant
      levels at any of the concentrations tested (10-100 microM). TTX was thus proved
      to be neither clastogenic nor aneugenic in the present study. It was, however,
      noteworthy that TTX at far lower concentrations, 0.1-5.0 microM, significantly
      enhanced the frequencies of SCE which indicated possible interference of the
      toxin in DNA replication and repair.

PMID- 9237773
TI  - Conversion of DNA damage into chromosome damage in response to cell cycle
      regulation of chromatin condensation after irradiation.
AB  - Cell fusion, premature chromosome condensation (PCC) and conventional
      cytogenetics were used to test whether the biochemical process of chromatin
      condensation-decondensation throughout the cell cycle, which depends on cyclin
      regulated histone H1 kinase activity, affects the conversion of DNA damage into
      chromosome damage and determines intrinsic cell cycle-stage radiosensitivity.
      Results from three sets of experiments are presented. Irradiated G0 human
      lymphocytes were fused to exponentially growing hamster cells and time allowed
      for repair, while following the hamster cells in their progress towards mitosis.
      Severe fragmentation was observed in the induced lymphocyte PCCs when hamster
      cells entered mitosis 13 h after irradiation, suggesting conversion of DNA damage
      into non-repairable chromosome damage during G1/S transition. When PCC was used
      to analyse chromosome damage directly in G0 and G2 phase lymphocytes, the
      induction of breaks per cell per chromatid per Gy was found to be similar,
      suggesting that G2 increased radiosensitivity is related to chromatin
      condensation occurring during G2/M transition and not to an inherent chromatin
      structure at this phase. When chromatin condensation-decondensation at the G1/S
      and G2/M transitions was modified after irradiation by using conditioned media or
      elevated temperature (40 degrees C), a dramatic change in the yield and the type
      of chromosomal aberrations was observed. All results obtained were consistent
      with the proposed hypothesis. They may be also helpful in the characterization of
      a DNA-chromosome damage conversion process which could give a biochemical
      explanation of the variability in radiosensitivity observed at the various stages
      of the cell cycle as well as among mutant cells and cells of different origin.
      The proposed conversion process is cell cycle-regulated and, therefore, subject
      to up-regulation or down-regulation following mutagen exposure and genetic
      alterations.

PMID- 9237775
TI  - Induction of micronuclei by smokeless tobacco on buccal mucosa cells of habitual
      users.
AB  - Maras Powder is a kind of smokeless tobacco widely used in lieu of cigarettes in
      the South-Eastern region of Turkey. In this study, we have evaluated micronuclei
      in buccal mucosa cells of habitual Maras Powder users. Therefore, we divided our
      subjects into three groups--smokeless tobacco users, smokers and non-smokers/non
      users. The mean percentage of micronucleated (MN) cells was significantly higher
      in smokeless tobacco users and smokers than in non-smokers/non-users (P < 0.01)
      [corrected]. The mean percentage of MN cells was 1.86 +/- 0.26 in users and 1.99
      +/- 0.30 in smokers. There was no difference between the mean percentage of MN
      cells in these two groups. In conclusion, the genotoxic effect of smokeless
      tobacco should be considered in addition to other known hazards.

PMID- 9237774
TI  - Survival, mutagenesis, and host cell reactivation in a Chinese hamster ovary cell
      ERCC1 knock-out mutant.
AB  - Positive selection-negative selection gene targeting was used to disrupt the
      nucleotide excision repair gene ERCC1 in a Chinese hamster ovary cell line, CHO
      K1. Southern and Northern analysis showed that a cell clone isolated by this
      targeting approach, CHO-7-27, had an ERCC1 gene structure consistent with
      targeted disruption of ERCC1 exon V, and did not express ERCC1 mRNA. CHO-7-27 was
      further characterized with respect to UV and mitomycin C sensitivities, and was
      shown to exhibit severe mutagen sensitivity phenotypes consistent with those of
      other CHO cell ERCC1 mutants. Mutation frequency experiments showed that CHO-7-27
      was UV-hypermutable at the hypoxanthine-guanine phosphoribosyltransferase locus.
      Experiments assessing host cell reactivation of viral DNA synthesis for UV
      irradiated adenovirus showed that CHO7-27 exhibited a severely deficient HCR
      phenotype similar to that of UV20 cells. Our results demonstrate that CHOK1 cells
      are hemizygous for the ERCC1 gene, and show that the comparatively mild mutagen
      sensitivities and lack of severely deficient HCR phenotypes of conventionally
      derived CHO-K1 ERCC1 mutants, in contrast to the severe phenotypes of CHO-AA8
      derived mutants, are not due to any intrinsic genetic differences between CHO-K1
      and CHO-AA8 parental cell lines.

PMID- 9237776
TI  - Moderate wine consumption protects against hydrogen peroxide-induced DNA damage.
AB  - We have tested the hypothesis that moderate wine drinking can protect somatic
      cells against the DNA-damaging effect of hydrogen peroxide which is an endogenous
      source of reactive oxygen metabolites. In this preliminary investigation, four
      male volunteers were placed on a plant-polyphenol-free (PPF) diet to ensure that
      the wine provided was the only main source of plant phenolic compounds. After 48
      h on the PPF diet the volunteers were required to consume 300 ml of red or white
      wine and blood samples collected 1, 3, 8 and 24 h post-consumption while still on
      a PPF diet. Plasma was isolated from the blood samples and stored frozen for
      subsequent assays. In the subsequent assays, fresh lymphocytes from each donor
      were incubated in their corresponding plasma from the various intervention time
      points for 30 min. The capacity of the plasma to prevent damage to DNA in
      lymphocytes by hydrogen peroxide was assessed using the cytokinesis-block
      micronucleus technique. The data from this preliminary investigation indicated
      that there was a strong inhibition (>70%) of hydrogen peroxide-induced
      micronucleated cells by the plasma samples from the blood collected 1 h after
      consumption of wine as compared to plasma samples from blood immediately before
      the consumption of wine. This protective effect was apparent for both red and
      white wine although statistical significance (P = 0.0068) was achieved only in
      the white wine intervention. A higher degree of statistical significance (P =
      0.0008) was achieved when the data for samples following the consumption of red
      and white wine were combined. There was no difference in the hydrogen-peroxide
      induced micronucleated cell frequency when comparing results immediately before
      starting on the PPF diet, before consumption of wine, 8 h after or 24 h after
      wine consumption. The hydrogen peroxide-induced micronucleated cell frequency in
      cells incubated with plasma from blood collected 3 h after wine consumption was
      intermediate to that observed for plasma after 1 and 8 h after wine intake. The
      protective effect of plasma against DNA damage cannot be readily explained by the
      red wine content of phenolic compounds because results for red wine were similar
      to those for white wine even though white wine had a much lower level of total
      polyphenols. A possible explanation could be that alcohol, glycerol and ascorbate
      in wine together with specific wine phenolic compounds that are also equally
      present in red and white wine (e.g. hydroxycinnamates) may have contributed to
      the observed protection of nuclear material from hydrogen peroxide-derived
      reactive oxygen metabolites. This explanation is supported by data from in vitro
      experiments showing that incubation of lymphocytes either with alcohol or wine
      stripped of phenolic compounds resulted in a statistically significant (P < 0.05)
      dose-related reduction (up to 87% reduction) in hydrogen peroxide-induced
      micronucleated cell frequency.

PMID- 9237778
TI  - Symposium on the significance of low level exposures to DNA adduct inducing
      chemicals, Department of Health, London, UK, May 1996.

PMID- 9237777
TI  - Inhibition of the genotoxic effects of heterocyclic amines in human derived
      hepatoma cells by dietary bioantimutagens.
AB  - The effects of dietary bioantimutagens (compounds which have been shown to
      inhibit mutagenesis via interaction with DNA repair processes) on spontaneous and
      heterocyclic amine (HCA)-induced micronucleus (MN) frequencies were studied in
      metabolically competent human hepatoma (Hep-G2) cells. All the compounds tested
      (coumarin, vanillin, caffeine, tannic acid and cinnamaldehyde) caused a moderate
      increase of MN numbers in Hep-G2 cells at high concentrations (500 microg/ml);
      only tannic acid was also active at lower dose levels. In combination experiments
      with the HCA 2-amino-3-methylimidazo-[3,4-f]quinoline (IQ), post-treatment of the
      cells with bioantimutagens resulted in a pronounced (75-90%) decrease in MN. The
      most drastic effects were seen with vanillin, coumarin and caffeine which were
      active at concentrations < or = 5 microg/ml. Further experiments indicated that
      these compounds also attenuate the mutagenic effects of other HCAs (PhIP, MeIQ,
      MeIQx, Trp-P-1).

PMID- 9237779
TI  - Gestational diabetes mellitus and gene mutations which affect insulin secretion.
AB  - We investigated whether genetic mutations known to impair insulin secretion and
      glucose tolerance are operative in a group of American women with gestational
      diabetes mellitus. Study groups were comprised of elderly non-diabetic controls
      (n = 55) with normal glucose tolerance and patients with gestational diabetes (n
      = 50), together with one family with maturity-onset diabetes of the young (three
      controls and three affected). No mutations were detected in any exon of the human
      glucokinase gene or the mitochondrial tRNA[Leu](UUR) gene by single strand
      conformational analysis and direct exon sequencing. Also, chi2 analysis showed no
      significant association with gestational diabetes for a polymorphism at position 
      30 (G --> A) of the beta-cell-specific glucokinase gene promoter. We have
      determined that glucokinase and mitochondrial tRNA[Leu](UUR) gene mutations,
      which are known to impair insulin secretion are relatively uncommon and do not
      constitute a large component of genetic risk for gestational diabetes in the
      study population.

PMID- 9237780
TI  - Acarbose controls postprandial hyperproinsulinemia in non-insulin dependent
      diabetes mellitus.
AB  - We investigated how fasting or postprandial insulin levels were altered by
      treatment with acarbose or sulfonylureas. Plasma glucose and serum insulin, C
      peptide, and proinsulin levels were measured before as well as 1 and 2 h after
      breakfast in 23 patients with non-insulin-dependent diabetes mellitus and 17
      patients with impaired glucose tolerance. In the diabetic patients, 12 weeks of
      acarbose therapy decreased the postprandial levels of glucose (1 h: -60.0%; 2 h: 
      67.6%), insulin (1 h: -67.5%; 2 h: -72.2%) and proinsulin (1 h: -55.2%; 2 h: 
      46.7%), and proinsulin (1 h: -20.9%; 2 h: -57.5%). In contrast, sulfonylurea
      treatment increased postprandial insulin and proinsulin levels. Since increased
      in the serum insulin or proinsulin levels are associated with a higher risk of
      cardiovascular disease, the present findings suggest that the acarbose-induced
      reduction of the postprandial serum insulin or proinsulin responses to food
      intake might be useful for preventing vascular complications in patients with
      diabetes.

PMID- 9237781
TI  - Postural stability of diabetic patients with and without cutaneous sensory
      deficit in the foot.
AB  - Postural stability was measured in 50 patients classified into two diabetic
      groups: insulin-dependent diabetes mellitus (IDDM: n = 27), and diabetic patients
      with bilateral cutaneous sensory deficit in the foot (CD: n = 23). All patients
      were matched to 50 non-diabetic controls on age, weight and gender variables. The
      integrity of cutaneous sensory information at the foot was assessed using a
      monofilament test. Static and dynamic balance was evaluated using an objective
      balance test involving computer-controlled dual force platforms enclosed by a
      visual surround. The apparatus provided six test conditions designed to
      systematically manipulate or eliminate visual, vestibular or somatosensory
      information. Scores for the six tests, and a derived composite balance score
      together with movement strategy scores were used for data analysis. For all six
      tests and composite score CD patients revealed significant postural instability
      compared to controls. Additionally, the CD group recorded reduced strategy scores
      indicating an atypical shift from ankle to hip strategy movement as postural
      control was stressed. IDDM patient test scores were not significantly different
      from control data on any pairwise comparison. Results indicated significant
      balance loss associated with CD putting the individual at increased risk for
      falling and compromising foot mechanics.

PMID- 9237782
TI  - The level of erythrocyte aldose reductase: a risk factor for diabetic neuropathy?
AB  - The level of erythrocyte aldose reductase protein (AR-p) was determined in
      diabetic patients as well as in 76 healthy controls by a two-site enzyme-linked
      immunosorbent assay. No significant difference in the mean AR-p level was
      demonstrated between the healthy and diabetic individuals. Based on the results
      of seven nerve function tests, 95 non-insulin-dependent diabetes mellitus (NIDDM)
      patients were classified into two groups: Group I, without demonstrable
      neuropathy ( < or = 1 abnormal test results); Group II, overt neuropathy ( > or =
      2 abnormal results). The AR-p level was significantly higher in Group II than
      that in Group I. Multivariate logistic regression analysis identified two
      independent risk factors for overt neuropathy: longer duration of diabetes after
      clinical diagnosis (odds ratio, 1.15 per year; 95% confidence interval, 1.05
      1.25) and a higher level of AR-p (odds ratio, 1.92 per 1 ng mgHb(-1); 95%
      confidence interval, 1.39-2.65). On 31 patients the AR-p level was re-assessed
      after a 12-month follow-up period. Irrespective of improved or stable HbA(1c)
      levels during the follow-up period, no apparent alteration in the level of AR-p
      was demonstrated. These results suggest that erythrocyte AR-p level may affect
      the susceptibility or development of diabetic neuropathy in NIDDM patients.

PMID- 9237783
TI  - Pen injection and change in metabolic control and quality of life in insulin
      dependent diabetes mellitus.
AB  - A second follow-up of metabolic control and quality of life in insulin dependent
      diabetes mellitus (IDDM) patients who had switched 3 years before from syringe to
      multiple pen injection treatment, was carried out. A total of 73 consecutive
      outpatients were enrolled in the initial follow-up study in 1988, 1 year after
      their changeover to insulin pen, with their metabolic control and quality of life
      examined. The present study concerns the reexamination of 65 of them in 1990.
      Their HbA(1c) level was recorded yearly, already from 1987, on. After an
      enhancement of metabolic control in 1988, exhibited primarily by patients with
      fewer syringe injections before pen treatment, control up to 1990 was found to
      have regressed to about baseline level or to have gradually declined. Patients
      who perceived their ability to self-test blood glucose to have decreased
      exhibited the least satisfactory course of metabolic control. This is seen to
      indicate that maintaining self-testing in multiple injection insulin treatment is
      a very real challenge to this regimen.

PMID- 9237784
TI  - Relationships of C-peptide levels and the C-peptide/bloodsugar ratio with
      clinical/biochemical variables associated with insulin resistance in orally
      treated, well-controlled type 2 diabetic patients.
AB  - The aim of the present study was to evaluate the relationship of C-peptide and
      the C-peptide/bloodsugar ratio with clinical/biochemical variables presenting a
      well-known association with insulin resistance in NIDDM patients in acceptable
      control, obtained without the use of exogenous insulin. A total of 118 non
      insulin dependent diabetes mellitus (NIDDM) patients treated with diet/oral drugs
      and having a HbA(1c) level < 7.5% have been studied. Non-stimulated C-peptide
      levels (RIA) and the C-peptide/bloodsugar ratio have been determined and their
      relationships with the blood pressure status, blood pressure figures, estimates
      of adiposity, age, known duration of diabetes, current therapies, plasma lipids,
      glycaemic control, urinary albumin excretion rate, uric acid and creatinine have
      been ascertained. C-peptide levels were significantly (P < 0.05) correlated with
      systolic (r = 0.21) and diastolic blood pressure (r = 0.19), BMI (r = 0.21), high
      density lipoprotein (HDL) (r = -0.22), non-HDL-cholesterol (r = 0.23),
      apolipoprotein B (r = 0.29), log of triglycerides (r = 0.39) and uric acid (r =
      0.35). The C-peptide/bloodsugar ratio had statistically significant correlations
      with known duration of diabetes (r = -0.23), diastolic blood pressure (r = 0.21),
      body mass index (BMI) (r = 0.22), log of triglycerides (r = 0.23) and uric acid
      (r = 0.36). Hypertensives had higher C-peptide levels than normotensives (1.04 +/
      0.04 versus 0.88 +/- 0.04 nmol/ml, respectively (mean +/- S.E.), P < 0.05) and
      this statistically significant difference remained after adjustment for age and
      known duration of diabetes. In well-controlled NIDDM patients not receiving
      exogenous insulin, both C-peptide levels and the C-peptide/bloodsugar ratio have
      statistically significant relationships with clinical/biochemical variables
      presenting a well-known association with insulin resistance.

PMID- 9237785
TI  - Effect of overweight and obesity on glucose intolerance and dyslipidemia in Saudi
      Arabia, epidemiological study.
AB  - The aim of this study was to study the effect of overweight and obesity on
      glucose intolerance and dyslipidemia in Saudi Arabia. A cross-sectional national
      epidemiological randomized household survey of 2059 Saudi subjects, aged 30-64
      years was carried out. The sample was representative and was in accordance with
      the national population distribution with respect to age, gender, regional and
      residency, urban versus rural population distribution. The subjects height and
      weight for the calculation of body mass index (BMI) was measured. Blood samples
      were drawn and assayed for glucose, total cholesterol, triglyceride and high
      density lipoprotein (HDL). Low density lipoprotein (LDL) was calculated. The oral
      glucose tolerance test was carried out for subjects with borderline random
      glucose concentration and the overall prevalence of diabetes mellitus was
      calculated. A high prevalence of obesity among the Saudi population was observed
      and mean serum glucose concentration was significantly higher among overweight
      and obese groups. The prevalence of diabetes mellitus was significantly higher
      among obese groups. The mean serum triglyceride concentration was only
      significantly higher among male obese groups. There was no significant difference
      in the mean of serum total cholesterol concentration between control and obese
      groups. Mean serum HDL concentration was lower among the obese group, however,
      the difference was not significant. There was no significant difference in the
      prevalence of hypercholesterolemia between control and obese groups. Prevalence
      of hypertriglyceridemia was higher among obese groups and was significantly
      higher among male subjects across all BMI groups. Prevalence of hypo HDL
      cholesterolemia exceeded 50% of the study population. Obesity, glucose
      intolerance, hypertriglyceridemia, hypo HDL cholesterolemia and features of
      insulin resistance syndrome (IRS) are widely prevalent among the Saudi population
      over the age of 40 years. IRS is probable a significant contributor to the
      pathologic process of cardiovascular (CVD) disease among the Saudi population,
      especially in view of the low prevalence of hypercholesterolemia.

PMID- 9237787
TI  - Experimental and clinical studies of the pathophysiology and management of acute
      spinal cord injury.

PMID- 9237786
TI  - Influences of The Great Hanshin-Awaji Earthquake on glycemic control in diabetic
      patients.
AB  - We investigated influences on glycemic control in 177 diabetic patients after The
      Great Hanshin-Awaji Earthquake which occurred on January 17, 1995. Changes in
      serum HbA(1c) level were studied according to the worsen rate of dietary and
      living conditions. A significant temporary increase in the mean value of HbA(1c)
      level was found after the earthquake (8.34 +/- 2.07% in March, 1995 vs. 7.74 +/-
      1.82% in December, 1994, P < 0.01). Ninety nine of them showed more than 0.5% in
      the rate of increase. Multiple regression analysis was applied to the following
      factors: inappropriate diet, discontinuation of drug uptake, reduction of
      exercise, destruction of house, long stay at shelter, sex, age, and pre
      earthquake therapy. Among them, inappropriate diet demonstrated the highest
      partial regression coefficient to raise the mean value of the HbA(1c) level. The
      increased level of HbA(1c) declined gradually to the pre-earthquake level in
      September, 1995. This study emphasizes the importance of appropriate diet for
      diabetic patients during a natural disaster. To fulfil it, medical staff have to
      educate diabetic patients of their disorders tediously in ordinary time. In
      addition, it seems quite useful to supply a medical information card and a small
      medical bag containing essential drugs to each patient.

PMID- 9237788
TI  - The role of glycine in spinal shock.
AB  - Suppression of increased muscle tone by epidural spinal cord stimulation, an
      invasive method for treating spasticity, increases segmental concentrations of
      inhibitory amino acid neurotransmitters, particularly glycine. The role of
      glycine in spasticity and spinal shock was explored further in rabbits with
      ischemic spinal cord injuries that produced spastic paraparesis or flaccid
      paraplegia. H-reflexes were monitored following posterior tibial nerve
      stimulation and plantar surface recording. Spasticity was quantified by using H/M
      ratios. Spastic animals were intrathecally infused with 100 mmol/l solutions of
      glycine and related compounds. Glycine agonists suppressed tone whereas glycine
      antagonists increased tone. In addition, microdialysis sampling from the cord was
      done in injured, non-infused animals and aspartate, GABA, glutamate, glycine and
      taurine were measured. Flaccid animals had glycine levels two-three times higher
      than spastic or control animals. High concentrations of glycine within spinal
      cord segments is associated with spinal shock. Glycine and related compounds may
      be useful as treatment for excessive tone.

PMID- 9237789
TI  - Do direct current electric fields enhance micturition in the spinal cat?
AB  - Changes in micturition behavior and motoneuron ultrastructure were studied in
      spinal cats to determine the effects of direct current (DC) electric field
      treatment. Adult cats received a complete injury at T8. A treatment group with an
      implanted 15 microA DC source and electrodes positioned near the lesion site was
      compared with non-treatment groups that were either operated or unoperated. Both
      bladder emptying with Crede and the withdrawal reflex were improved in the
      treatment group compared with the non-treatment group. Urodynamic procedures
      showed that high urethral resistance and pelvic floor activity following spinal
      injury was partially reduced in the stimulated cat, indicating inhibition of the
      urethral sphincter. The ultrastructural analysis of Onuf's nucleus suggested a
      similar synaptic input in all three groups. In conclusion, possible activation of
      inhibitory processes and/or neural plasticity best explain the early improvement
      of bladder function seen following electrical stimulation.

PMID- 9237790
TI  - The raccoon as an animal model for upper limb neural prosthetics.
AB  - The raccoon was evaluated as an animal model for upper limb neural prosthetics.
      This animal was selected primarily because the functional use of its forelimb
      mimics in many ways the usage in humans and because of its optimal size and
      commercial availability. Eight cadaver and fresh specimen forearms were
      dissected. Important characteristics of the raccoon forearm were: 1) large
      muscles in the volar forearm, 2) large digits in the paw that appear more similar
      to humans than to other species such as cat or dog, 3) persistence of two median
      nerve cords into the forearm, 4) no separation of individual tendons of flexor
      digitorum superficialis and flexor digitorum profundus in the carpal tunnel, 5) a
      small thumb digit with little function and 6) a primary origin of flexor policis
      longus on the proximal ulna with a secondary origin on the radius. Four animals
      were anesthetized and responses of the forearm and paw to stimulation of the
      volar forearm muscles with percutaneous electrodes were evaluated. A pair of
      stimulating electrodes was placed in each of four muscles or muscle groups.
      Recording electrodes were placed in two muscles which showed the greatest
      separation of muscle movements to stimulation. Stimulation currents just above
      threshold produced discrete motion as well as recordable EMG M-waves. Incremental
      increases in stimulation current produced an increase in M-wave amplitude up to a
      maximal stimulating current. Torque recordings for pronation, wrist flexion and
      finger flexion showed graded and selective responses. These results including
      anatomical descriptions indicate both the limitations of this animal model and
      its potential use in the development of upper limb neural prosthetics. We
      conclude that the raccoon model may be superior to other nonprimate animal models
      such as the cat because of its extensive forearm and paw movements.

PMID- 9237791
TI  - Spinal cord infarction: varying degrees of upper and lower motoneuron
      dysfunction.
AB  - Five patients with spinal cord infarction underwent electrophysiologic
      evaluation. Two subjects with complete paralysis had absent compound muscle
      action potentials (M-responses), suggesting complete loss of lower motoneurons
      (LMN). Three subjects with incomplete cord infarction had preserved M-responses,
      reduced voluntary recruitment and abnormally slow motor-unit firing rates during
      maximal effort, suggesting upper motoneuron (UMN) weakness. These five patients
      demonstrate a range of neuronal damage after cord ischemia. With severe cord
      infarction, there is LMN degeneration and paralysis. With partial cord
      infarction, there is selective interneuron loss, resulting in UMN weakness.
      Electrodiagnostic evaluation can help determine prognosis for motor recovery
      after spinal cord infarction.

PMID- 9237792
TI  - Characterization of the bone mineral density of children with spinal cord injury.
AB  - The purpose of this study was to compare the bone mineral density in children
      with spinal cord injury (SCI) with age- and sex-matched controls in three
      anatomic areas of the proximal hip. In addition, post hoc analysis looked for
      differences in bone density between sub-groups considering several factors
      associated with spinal cord injury: the presence or absence of spasticity, the
      level of injury and the presence or absence of pathologic fractures. Fifty-one
      pediatric patients with spinal cord injury between the ages of 3 and 20 underwent
      bone density measurements using dual photon absorptiometry. Before pooling the
      data across age groups, all measurements were normalized to age- and sex-matched
      controls because of increasing bone density with growth and higher bone density
      in males. The results revealed lower bone densities in subjects with SCI as
      compared with their non-disabled peers, ranging from 56 percent to 65 percent of
      normal across the three anatomic regions. On the average, subjects who had a
      previous history of fractures had significantly lower bone density measurements
      than those without fractures. At the intertrochanteric region, a 10.6 percent
      difference was noted between subjects with tetraplegia versus those with
      paraplegia. At the femoral neck and Ward's Triangle, an 8.5 percent difference
      was noted between subjects with and without spasticity. No conclusions could be
      drawn from the analyses at the other sites. Together these results begin to
      characterize bone density levels of the pediatric SCI population.

PMID- 9237793
TI  - Autonomic hyperreflexia associated with exacerbation of reflex sympathetic
      dystrophy.
AB  - Autonomic hyperreflexia is a condition of massive paroxysmal reflex sympathetic
      outflow in response to noxious stimuli occurring below the major splanchnic
      sympathetic outflow in patients with spinal cord injuries. This heightened
      sympathetic outflow can result in dramatic sudomotor and vasomotor
      manifestations. The unique nature of this sympathetic-mediated response following
      traumatic spinal cord injury provides a model for the study of the autonomic
      nervous system in normal and pathological conditions. A case of autonomic
      hyperreflexia exacerbating the pain of reflex sympathetic dystrophy in a patient
      with tetraplegia illustrates the role of the sympathetic nervous system in the
      pathophysiology of sympathetic-mediated pain and supports current treatment
      options for these conditions.

PMID- 9237794
TI  - T-cell lymphocytic lymphoma involving the prostate presenting as elevated PSA in
      paraplegia: case report.
AB  - The vast majority of cancers that involve the prostate are adenocarcinomas of the
      duct-acinar secretory epithelium. Other cancers, primarily leukemia and lymphoma,
      can involve the prostate and lead to an abnormal digital examination or elevated
      serum prostate specific antigen (PSA). The case discussed is that of a 62 year
      old male with T12 complete paraplegia who presented with a persistently elevated
      PSA and was subsequently diagnosed with T-cell lymphoma involving the prostate.
      Although rare, leukemia and lymphoma involving the prostate should be included in
      the differential diagnosis of patients being evaluated for adenocarcinoma of the
      prostate.

PMID- 9237795
TI  - Treatment of NOD diabetes with a novel peptide of the hsp60 molecule induces Th2
      type antibodies.
AB  - A peptide from the sequence of hsp60 molecule, designated p277, has been shown to
      be functionally involved in modulating the development of auto-immune diabetes in
      the NOD mouse: administration of p277 to NOD mice can arrest the diabetogenic
      autoimmune process, even when far advanced. Is p277 the only hsp60 peptide able
      to modulate the disease? We mapped T cell responses to peptides spanning the
      mouse hsp60 molecule and identified an immunogenic peptide, designated p12, that
      is also functional in arresting NOD diabetes. Although no spontaneous T cell
      reactivity to p12 could be detected in NOD mice, subcutaneous administration of
      100 microg of p12 in mineral oil to 10-week-old female NOD mice, similar to
      treatment with p277, significantly prevented progression of the disease.
      Administration of other immunogenic peptides was not effective. A peptide from
      the glutamic acid decarboxylase (GAD65) sequence, GADp35, and a peptide from the
      myco-bacterial hsp60 molecule did not influence the development of diabetes. The
      effectiveness of hsp60 peptides p12 and p277 was associated with the induction of
      antibodies to the peptides of the IgG1 and IgG2b isotypes, antibodies which
      appear to be regulated by anti-inflammatory cytokines. There was a negative
      correlation between the amounts of antibodies induced by the hsp60 peptides and
      the level of blood glucose. Thus, more than one peptide of the hsp60 molecule can
      be used to inhibit the development of NOD diabetes, and the effect of peptide
      therapy appears to be associated with the induction of specific antibody
      isotypes.

PMID- 9237796
TI  - Regulation of autoimmune diabetes by interleukin 3-dependent bone marrow-derived
      cells in NOD mice.
AB  - Interleukin-3 (IL-3), a multilineage colony stimulating factor, has been shown to
      augment alloreactive bone marrow-derived suppressor cell activity in vivo and in
      vitro. The present study examined the effect of IL-3 on autoimmune-mediated
      diabetes in NOD mice. Administration of IL-3 twice weekly starting at 2-4 weeks
      of age delayed the onset and reduced the overall incidence of diabetes. Bone
      marrow cells obtained from IL-3-treated NOD mice protected NOD mice from
      cyclophosphamide-induced diabetes but failed to prevent adoptively transferred
      diabetes. In vitro culture of bone marrow cells in medium containing IL-3
      produced a Thy-1+CD3epsilonloCD4-CD8-CD25- immature T cell clone which prevented
      cyclophosphamide-induced diabetes. The cloned cells also effectively delayed the
      development of diabetes induced by transfer of T cells in adult thymectomized,
      irradiated, bone marrow-reconstituted NOD mice. These results suggest that IL-3
      is capable of regulating extrathymic T cell development from the bone marrow and
      that these cells mediate strong immunoregulatory function.

PMID- 9237797
TI  - Oral administration of the immunodominant B-chain of insulin reduces diabetes in
      a co-transfer model of diabetes in the NOD mouse and is associated with a switch
      from Th1 to Th2 cytokines.
AB  - Oral administration of antigen leads to systemic immune unresponsiveness. Low
      dose oral tolerance generates regulatory cells which, when triggered in an
      antigen-specific manner, suppress inflammatory responses. We have previously
      shown that oral administration of an organ-specific antigen, porcine insulin,
      protects against diabetes development in the NOD mouse. In the present study we
      extend these observations to the B-chain of insulin, a 30-amino-acid peptide
      which has now been shown by others to contain the immunogenic epitope. Oral
      administration of the B-chain slowed diabetes development in a co-transfer model
      in which cells from B-chain-fed animals were co-transferred with diabetogenic
      cells (P=0.02). Further exposure to antigen via feeding of the co-transfer
      recipient animals not only slowed diabetes development but prevented diabetes in
      some animals (P=0.01). In vitro proliferation of popliteal lymph node cells from
      fed and immunized animals was suppressed in an antigen-specific manner when cells
      were restimulated with the fed antigen. When those cells were cultured and
      restimulated in vitro with the B-chain of insulin, we also observed a decrease in
      IFN-gamma expression and an increase in IL-4, TGF-beta and IL-10 expression.
      These results demonstrate that an orally protective epitope resides in the B
      chain of insulin and that refeeding following adoptive transfer enhances
      protection. Finally, the orally administered antigen is associated with a
      decrease in Th1 responses and an increase in Th2 responses to the insulin B
      chain.

PMID- 9237798
TI  - Effects of the murine genotype on T cell activation and cytokine production in
      murine mercury-induced autoimmunity.
AB  - Mercury induces a systemic autoimmune condition characterized by auto-antibodies
      to the nucleolar protein fibrillarin (AFA) and systemic immune-complex (IC)
      deposits in genetically susceptible mouse strains. This study examines T cell
      activation and cytokine production following mercury exposure in genetically
      susceptible and resistant strains. Mercury injected s.c., according to the
      protocol for induction of autoimmunity, caused an early T cell activation,
      measured as an increase of IL-2-producing cells, and increased expression of the
      IL-2-receptor proteins CD25 and CD122 and of the proliferation marker CD71 on
      days 2-4 in the susceptible A.SW and A. TH strains. This was followed by a long
      lasting increase in the number of T cells, dominated by CD4(+) cells. Mice of the
      susceptible A.SW strain showed a modest increase of TNF-alpha-, IFN-gamma-, and
      IL-4-producing cells after 4-6 days, and a very distinct increase of IL-4
      producing cells on days 8-10. The susceptible SJL strain (H-2(s)), severely
      deficient in Th2-promoting CD4(+), NK1.1(+) T cells, showed no increase of IL
      4(+) cells on days 8-10. Instead, the number of IFN-gamma-producing cells was
      increased. Susceptible mice developed an increase of Ig-producing cells, AFA, and
      systemic IC-deposits. Genetically mercury-resistant A.TL mice showed a minimal
      increase of T cells, but no increase in cytokine-producing cells. We conclude
      that autoimmunogenic doses of HgCl2 induce an activation and proliferation of T
      cells in genetically susceptible mouse strains, as well as a broad increase of
      cytokine-producing cells, followed by a late predominance of the Th2-associated
      IL-4. One strain, severely deficient in Th2-promoting CD4(+), NK1.1(+) T cells,
      lacked the increase in IL-4(+) cells, indicating that a predominantly Th2
      response is not necessary for induction of autoimmunity by mercury. However, a
      Th2-dominated response led to a faster and stronger B cell activation.

PMID- 9237799
TI  - Memory T cell tolerance to superantigens is not due to increased susceptibility
      to apoptosis.
AB  - Naive (virgin) and memory T lymphocytes differ markedly in their response to
      superantigens (SAg). When cultured with the SAg staphylococcal enterotoxin B
      (SEB), virgin but not memory CD4(+) T cells proliferate and secrete lymphokines.
      Memory cells do express increased levels of activation markers after interaction
      with SEB, which suggests that the cells are not ignorant of the SAg. In this
      report, we have considered whether SEB, rather than activating memory cells,
      promotes their death by apoptosis. Our results indicate that while in vivo
      exposure to SEB induces apoptosis, there is no greater level of cell death in the
      memory cell population relative to virgin cells. Further, elimination of the Fas
      mediated cell death pathway does not permit memory cells to be stimulated by SEB.
      Memory T cells from either Fas-expressing or Fas-deficient (MRL-lpr/lpr) mice are
      hyporesponsive to SEB. Blockade of Fas/Fas-ligand interactions by a Fas-Fc
      chimeric protein does not permit BALB/c memory cells to proliferate upon culture
      with SEB. These results provide evidence that the failure of memory T cells to
      respond to SEB is not due to cell death and that inactivation (anergy) is the
      likely fate of these cells when they encounter SEB.

PMID- 9237800
TI  - Effects of oral administration of malathion on the course of disease in MRL-lpr
      mice.
AB  - Malathion administration at non-cholinergical doses was shown to elevate
      macrophage, proliferative and humoral immune responses. This study examined the
      effects of malathion on autoimmunity, autoantibody formation, macrophage function
      and mitogenic responses in MRL-lpr mice (genetically predisposed to autoimmune
      disease) and MRL-+/+ mice. Malathion, 33-300mg/kg, was administered by gavage
      once per week, beginning at 6 weeks of age. At 300mg/kg in MRL-lpr mice,
      malathion administration accelerated the appearance of significant (>100mg/l)
      levels of urinary protein by approximately 3 weeks and increased the maximum
      level of protein detected. Increased urinary protein was delayed at lower doses
      of malathion, but was elevated compared to vehicle control. This increase in
      urinary protein was not observed in the group of MRL-+/+ mice. The popliteal and
      axillary lymph nodes (LN) were larger in malathion-treated (>33mg/kg) than in
      control mice at 19 weeks of age. Within the same time-frame in MRL-+/+ mice,
      malathion did not affect and increased the size of the axillary and popliteal LN,
      respectively. Rheumatoid factor (RF) and anti-DNA (dsDNA) antibodies in the serum
      were not elevated in any group of MRL-+/+ mice by 19 weeks of age. However, in
      the MRL-lpr mice, weekly malathion treatment (>33mg/kg) elevated the level of
      serum RF at 12 and 19 weeks of age. Malathion treatment (>100mg/kg) also
      increased the level of anti-dsDNA antibodies in the serum of MRL-lpr mice at 19
      weeks of age. Malathion treatment increased the number of inflamed glomeruli.
      Histopathological analysis of various organs showed no effect on vasculitis after
      malathion treatment. Acute administration of 300mg/kg malathion to 6-week-old
      mice elevated the secretion of nitric oxide by peritoneal macrophages, but did
      not affect the secretion of tumor necrosis factor. In addition, the basal and
      mitogen-induced proliferation of splenocytes of malathion-treated MRL-lpr mice
      were elevated, but the stimulation index was unchanged.

PMID- 9237801
TI  - High affinity presentation of an autoantigenic peptide in type I diabetes by an
      HLA class II protein encoded in a haplotype protecting from disease.
AB  - Polymorphism of the genes coding for the human histocompatibility leukocyte
      antigen class II DR and DQ molecules makes the single largest genetic
      contribution to the risk of developing insulin-dependent diabetes mellitus (IDDM)
      and can be associated with highly elevated as well as decreased disease
      frequency. The mechanism of IDDM risk modification by HLA polymorphism is likely
      to involve differential presentation of autoantigenic peptides by HLA class II
      proteins. We have generated T cell lines (TCL) with specificity for the IDDM
      autoantigen 65 kDa glutamic acid decarboxylase (GAD65) from lymphocytes of two
      patients carrying HLA class II alleles associated with distinct risk of IDDM
      (DRB1*0101/0401 and 1302/1501). For both patients, TCL generated at various time
      points all recognized single epitopes mapped as GAD 88-99 and 248-257,
      respectively. These epitopes are presented by the DRB1*0101 and DRB5*0101, HLA
      class II molecules associated with a moderately elevated risk of IDDM, or carried
      in a strongly protective haplotype, respectively. In an HLA/peptide binding
      assay, epitope GAD 248-257 was shown to possess high affinity for DRB5*0101. This
      epitope overlaps with a central GAD peptide binding to the high risk allele
      DQB1*0302 and containing a Coxsackie P2C-identical mimicry sequence, raising the
      possibility of competition of DRB5*0101 and DQB1*0302 for binding of a central
      GAD65 fragment.

PMID- 9237802
TI  - Characterization of a human T cell line reactive to a 52 kDa islet protein.
AB  - A 52 kDa islet protein has recently been identified as the target of
      autoantibodies in the NOD mouse model of IDDM and humans with IDDM. However, the
      presence of T cell immunity against the 52 kDa islet protein in IDDM has not been
      reported. We report the establishment and characterization of a T cell line
      (19KW) that reacts to purified 52 kDa islet protein (purified p52) from a subject
      with IDDM. The purified p52 induced a proliferative response as measured by
      thymidine incorporation in the 19KW T cell line with a stimulating index of up to
      48. The proliferative responses were greater with increasing doses of purified
      p52 (0.1, 0.5, 2.0, and 6.0 microg/well). No reactivity was found to a liver
      fraction purified in the same manner as 52 kDa protein, BSA, ovalbumin, extracts
      of rat muscle, fibroblast, adrenal, or pituitary tissue and to a rat exocrine
      cell tumor. Irradiated PBMC were required as antigen presenting cells (APC) for
      19KW reactivity to the purified p52. The addition of anti-HLA DR or anti-HLA DQ
      antibodies significantly decreased the islet antigen-induced proliferative
      response. The addition of antibodies to HLA DP and class I MHC had no effect.
      Flow cytometric analysis revealed that the majority of T cells expressed CD4 and
      CD45RO molecules. T cell receptors Vbeta6 and Vbeta5.1 were found on 30 and 14%
      of the CD3+ (T cells) 19KW cells, respectively. In conclusion, a purified p52
      reactive human T cell line predominantly consisting of TCR Vbeta6+ and Vbeta5.1+
      cells has been established from a subject with IDDM. Reactivity to the purified
      p52 is antigen dose-dependent, tissue specific, requires irradiated PBMC as
      antigen presenting cells, and is HLA DR- and HLA DQ-restricted. T cell lines
      specifically reactive to p52 may be useful for investigating further the role of
      this antigen in the pathogenesis of IDDM.

PMID- 9237803
TI  - Lack of association of DMB polymorphism with insulin-dependent diabetes.
AB  - Considerable evidence exists that the genes coding for the HLA class II DQ
      molecules in the MHC region are major contributors to genetic susceptibility in
      insulin-dependent diabetes. Located centromeric to the DQ loci are the genes
      encoding DMA and DMB, two class II-like molecules which play an essential role in
      the pathway leading to antigen presentation by HLA class II. In this study we
      have examined the distribution of the DMB allele and studied HLA DQA1-DQB1-TAP2
      DMB haplotypes in 52 IDDM families and 65 un-related controls. DMB allele
      frequencies in IDDM and control subjects were not significantly different.
      DMB*0101 was present in 85% of patients vs. 76% of controls, DMB*0102 in 12 vs.
      17%, DMB*0103 in 3 vs. 5%, DMB*0104 in 0 vs. 2%. The IDDM-susceptible MHC DQA1
      DQB1 haplotypes found by analysis of IDDM families were not associated with
      specific DMB alleles. We conclude that the described DMB polymorphisms are not
      associated with IDDM susceptibility and DMB genotyping is unlikely to improve the
      assessment of genetic risk for IDDM.

PMID- 9237804
TI  - Decreased beta2-adrenergic receptor density on peripheral blood mononuclear cells
      in myasthenia gravis.
AB  - Beta2-adrenergic receptors (beta2AR) are present on both lymphocytes and skeletal
      muscle cells. Antibodies and T cells that react with these receptors are present
      in patients with myasthenia gravis (MG). Immune reactivity against the beta2AR
      may thus modify both the immune and the muscle functions in MG. In this study, we
      analysed the density and affinity of beta2AR on peripheral blood mononuclear
      cells using a radioligand binding assay. The density (Bmax) of the receptor on
      cells from patients with MG was significantly lower than that on cells from
      patients with other neurological disorders and healthy individuals. The affinity
      (Kd) of the receptor and the concentration of the second messenger, cAMP, in the
      cells did not differ between the groups. Serum antibodies against beta2AR were
      demonstrated in 22% of 27 MG patients vs. 0% of 26 healthy controls. Incubation
      of cells with serum or purified IgG containing antibodies against the beta2AR
      resulted in a decline in ligand binding of the receptor in samples from three out
      of five patients. Thus, this study suggests that a downregulation of the beta2AR
      may occur in MG. This downregulation might be of importance in the patho-genesis
      of the disease and its symptoms.

PMID- 9237805
TI  - Association of the AChRalpha-subunit gene (CHRNA), DQA1*0101, and the DR3
      haplotype in myasthenia gravis. Evidence for a three-gene disease model in a
      subgroup of patients.
AB  - Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction
      having multigene control. HLA-linked loci and the HB*14 micro-satellite marker
      located within the CHRNA gene which encodes the muscular acetylcholine receptor
      (AChR) alpha-subunit, the target self-antigen, were previously associated with
      MG. Combined analysis of these loci revealed a significant increase of DQA1*0101
      alleles in HB*14+ vs. HB*14- patients and of DQA1*0501 alleles in HB*14/DQA1*0101
      patients. Importantly, the effect of DQA1*0101 was independent of allelically
      associated DQB1 and DRB1 genes. In contrast, the effect of DQA1*0501 could not be
      dissociated from that of DRB1*03 and DQB1*0201 on the extended DR3 haplotype.
      These results indicate that a combination of three genes, of which two are linked
      to HLA, contributes to disease susceptibility in a subgroup of MG patients.

PMID- 9237806
TI  - Correlation between anti-C1q and immune conglutinin levels, but not between
      levels of antibodies to the structurally related autoantigens C1q and type II
      collagen in SLE or RA.
AB  - The simultaneous appearance of autoantibodies with either a functional or
      structural relationship to anti-C1q antibodies (anti-C1q) was investigated in 39
      systemic lupus erythematosus (SLE) patients and in 28 rheumatoid arthritis (RA)
      patients, in both cross-sectional and longitudinal design. Levels of anti-C1q
      showed an isotype-specific correlation to levels of immune con-glutinin (IK) in
      SLE patients, whereas no correlation was evident to levels of antibodies to the
      structurally related antigen type II collagen (anti-CII) in SLE or RA patients.
      IgG anti-C1q levels correlated with serum levels of the terminal complement
      complex (sC5b-9) in SLE patients. In two longi-tudinally followed patients, the
      IK response preceded the anti-C1q response. Possibilities for regulation of the
      humoral anti-complement response are discussed.

PMID- 9237807
TI  - Effect of interleukin 1 and leukaemia inhibitory factor on chondrocyte metabolism
      in articular cartilage from normal and interleukin-6-deficient mice: role of
      nitric oxide and IL-6 in the suppression of proteoglycan synthesis.
AB  - We studied the role of IL-6 and nitric oxide (NO) in IL-1 and leukaemia
      inhibitory factor (LIF) induced suppression of proteoglycan synthesis. Cartilage
      explants of patellae and femoral heads were incubated with IL-1 or LIF.
      Conditioned media were analysed for IL-6 activity (B9-assay) and NO content
      (Griess). Proteoglycan synthesis was assessed using [35S]sulfate incorporation.
      IL-1 dose dependently induced IL-6 synthesis and neutralizing IL-6 with
      antibodies did not reduce proteoglycan synthesis suppression, neither in explants
      nor in isolated chondrocytes. IL-6 independence was confirmed using cartilage
      from IL-6 deficient mice. IL-1 significantly increased NO release in normal and
      IL-6 deficient chondrocytes and addition of the NO synthase inhibitor, N(G)
      monomethyl-L-arginine markedly alleviated proteoglycan synthesis suppression. LIF
      also induced proteoglycan synthesis suppression in cartilage from normal and IL-6
      deficient mice, but the suppression was neither accompanied by nor dependent on
      NO release. Furthermore, proteoglycan synthesis suppression during experimental
      arthritis was similar in both normal and IL-6 deficient mice. We concluded that
      IL-6 is not a necessary cofactor in IL-1 and LIF induced suppression of
      proteoglycan synthesis. Furthermore, only the IL-1 induced suppression was
      mediated by NO, suggesting that inhibition of proteoglycan synthesis may occur
      through different pathways.

PMID- 9237808
TI  - TNF-alpha-induced apoptosis in Daudi cells: multiparametric analysis.
AB  - Tumour necrosis factor alpha (TNF-alpha) is a cytokine that induces physiological
      and pathophysiological effects in the immune system. In this study we analyzed
      its action on a human lymphoma cell line (Daudi cells) after 1 h, 6 h and 24 h of
      incubation. Using vital DNA stains, DNA gel electrophoresis, in situ nick
      translation, transmission electron microscopy and flow cytometry we showed that
      as early as after 6 h of treatment, target cells were able to undergo death by
      apoptosis. This was associated with cell shrinkage, chromatin condensation,
      apoptotic bodies in the cytoplasm without the typical DNA fragmentation into low
      molecular weight nucleosomes. Of interest was the observation of a significant
      number (60%) of cells positive to the nick translation in specimens treated for 6
      h, decreasing to 40% in samples treated for 24 h, when most of the cells were in
      late apoptosis. In addition, no subdiploid peak was evident in flow cytometry
      regardless of the time of incubation with TNF. Our study on Daudi cells clearly
      supports the existence of alternative forms of apoptosis in which DNA degradation
      does not result only in oligonucleosomal fragmentation.

PMID- 9237809
TI  - Specific detection of an interleukin 1- and tumour necrosis factor-activated beta
      casein kinase in HeLa and KB cells.
AB  - Interleukin 1 (IL-1) and tumour necrosis factor (TNF) activate a novel protein
      kinase, TIP kinase, which phosphorylates beta-casein in vitro. We have identified
      and purified to homogeneity a tryptic fragment of beta-casein, called T1, which
      was phosphorylated by TIP kinase with kinetics similar to those of the intact
      protein (K[m] = 27 +/- 6 microM). Phosphopeptide maps of in vitro phosphorylated
      T1 and beta-casein were identical, confirming that T1 contained the main
      phosphorylation site of the protein. T1 corresponded to residues 114 to 169 of
      beta-casein. It was phosphorylated by constitutively active protein kinases to a
      much lesser extent than beta-casein and thus constituted a specific substrate of
      the cytokine-activated enzyme. This made possible the detection of TIP kinase in
      extracts of IL-1-stimulated HeLa and KB cells, which had been hampered by high
      background phosphorylation when beta-casein was used as substrate. Our results
      show that the use of fragment T1 allows detection of low levels of TIP kinase in
      crude samples. They also suggest that its activation, which had previously been
      observed only in connective tissue cells, may be a general response of many cell
      types to IL-1 or TNF.

PMID- 9237810
TI  - Direct contact with stimulated T cells induces the expression of IL-1beta and IL
      1 receptor antagonist in human monocytes. Involvement of serine/threonine
      phosphatases in differential regulation.
AB  - Imbalance in the production of cytokines and their inhibitors plays a part in
      inflammation in chronic destructive diseases. Direct cell-cell contact with
      stimulated T cells markedly induces the production of pro-inflammatory cytokines
      and matrix metalloproteinases in monocytes. This study demonstrates that direct
      contact with stimulated T cells favours the production of IL-1beta over that of
      IL-1 receptor antagonist (IL-1Ra) in both peripheral blood monocytes and the
      monocytic cell line THP-1. In contrast, soluble factors secreted by stimulated T
      cells favour the production of IL-1Ra. Differentiation of THP-1 cells with 1,25
      (OH)2D3 did not affect the balance between IL-1beta and IL-1Ra production,
      enhancing both cytokines 2.3- and 1.6-fold, respectively. Among different
      inhibitors of phosphorylation and dephosphorylation processes, only okadaic acid,
      an inhibitor of serine/threonine phosphatases, differentially modulates the
      production of IL-1beta and IL-1Ra. Indeed, okadaic acid upregulated IL-1beta and
      decreased IL-1Ra at the mRNA and protein level in monocytic cells activated by
      membranes of stimulated T cells. These results suggest that serine/threonine
      phosphatases play a part in the differential regulation of the production of IL
      1beta and IL-1Ra by monocytes upon direct cell-cell contact with stimulated T
      cells. This mechanism may regulate the balance between the pro-inflammatory
      cytokine and its inhibitor, which balance dictates in part the outcome of the
      inflammatory process.

PMID- 9237811
TI  - Analysis of human IL-2/IL-2 receptor beta chain interactions: monoclonal antibody
      H2-8 and new IL-2 mutants define the critical role of alpha helix-A of IL-2.
AB  - Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits
      (IL-2R alpha, IL-2R beta and IL-2R gamma). IL-2R beta plays a critical role in
      signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization
      with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20, at
      the exposed interface between alpha-helices A and C. Muteins at position 17 and
      20 are not recognized by mAb H2-8. mAb H2-8 specifically inhibits the IL-2
      proliferation of TS1beta cells which are dependent on the expression of human IL
      2R beta chain for IL-2 proliferation. Substitution at internal position Leu17
      demonstrates that this position is essential for IL-2 binding and IL-2
      bioactivity. New IL-2 mutants at position Asp20 have been analysed. Substitutions
      Asp --> Asn, Asp --> Lys, Asp --> Leu, show a correlation between diminished
      affinity for IL-2 receptor and reduced bioactivity measured on TS1beta cells.
      Mutein Asp Arg lose affinity for IL-2R and bioactivity simultaneously.
      Furthermore, during the course of the study we have found that mutein Asp20 -->
      Leu is an IL-2 antagonist. The biological effects of mAb H2-8 and the properties
      of new mutants at positions 17 and 20 demonstrate that this region of alpha helix
      A is involved in IL-2-IL-2R beta interactions.

PMID- 9237812
TI  - Interleukin 12 and B7/CD28 interaction synergistically upregulate interleukin 10
      production by human T cells.
AB  - Interleukin 12 (IL-12) is a heterodimeric cytokine which promotes the development
      of Th1 cells and their interferon gamma (IFN-gamma) production after TCR/CD3
      triggering. Previous reports indicate that IL-12 synergizes with accessory
      signalling through B7/CD28 interaction in inducing proliferation and IFN-gamma
      production by human T cells. In this study, we investigated the capacity of IL-12
      to modify cytokine synthesis by freshly purified human peripheral blood T cells
      stimulated with anti-CD3 as the primary signal and with CD80 on transfected mouse
      cells as an accessory signal. Our data demonstrate that IL-12 indeed synergizes
      with B7/CD28 interaction, not only in inducing IFN-gamma production, but also in
      enhancing IL-10 synthesis in a dose-dependent manner. In contrast, IL-4 and IL-5
      production were slightly inhibited by IL-12. The effect of IL-12 on the secretion
      of IL-10 was confirmed by stimulating T cells in the absence of accessory cells
      with immobilized anti-CD3 mAb and soluble anti-CD28 mAb. CD80 and IL-12 mainly
      costimulated CD4+CD45RO+ T cells but not CD8+ or CD45RA+ T cells to produce IL
      10. Cyclosporin A (CsA) partially inhibited, and a neutralizing anti-IL-2 mAb in
      combination with anti-IL-2R mAbs (anti-Tac and Mik beta1) strongly reduced IL-10
      production. On the other hand, IL-12 did not affect IL-2 production. The data
      thus suggest a model in which optimal IL-10 production by stimulated peripheral
      blood T cells results from the co-operation of IL-12, B7/CD28 interaction and the
      ensuing IL-2 activity.

PMID- 9237813
TI  - Differential regulation of human T lymphoblast functions by IL-2 and IL-15.
AB  - Interleukin 15 (IL-15) shares many functional properties with interleukin 2 (IL
      2), although both cytokines probably also exert distinct functions. In order to
      screen for functional differences between IL-2 and IL-15 with respect to the
      control of T cell functions, we have stimulated human T lymphoblasts (hTBl) with
      IL-2 and/or IL-15 and have assessed the resulting changes in the following
      parameters: T cell proliferation; expression of various relevant surface markers;
      cytokine and receptor (alpha-chain) transcription; and IL-2 and IL-15 activity.
      Both cytokines equally upregulate standard activation markers such as CD25 and
      CD95 and downregulate CD27. However, IL-2 upregulates CD30, TNF receptor type II
      and CD40L expression significantly stronger than IL-15. IL-15 potentiates Con A
      induced IL-2 secretion. Even though hTBl transcribe the IL-15 gene, they do not
      secrete IL-15 activity. These observations suggest that both cytokines can
      differentially regulate T cells, e.g. T cell functions relevant to the control of
      cell cycle progression and apoptosis, and/or that they can stimulate different T
      cell subsets. Moreover, IL-15 may potentiate IL-2-driven T cell responses.

PMID- 9237814
TI  - Stimulation of IL-8 production in human gastric epithelial cells by Helicobacter
      pylori, IL-1beta and TNF-alpha requires tyrosine kinase activity, but not protein
      kinase C.
AB  - Production of interleukin 8 (IL-8) is believed to be important in the
      pathogenesis of the gastritis seen in Helicobacter pylori infection. The aim of
      this study was to investigate the roles of protein kinase A (PKA), protein kinase
      C (PKC), protein tyrosine kinase (PTK) and intracellular calcium in the induction
      of IL-8 production by gastric epithelial cells. AGS gastric epithelial cells were
      stimulated with H. pylori, tumour necrosis factor alpha or interleukin 1beta
      together with activators or inhibitors of the relevant kinases. IL-8 production
      was measured by enzyme-linked immunosorbent assay. Helicobacter pylori, tumour
      necrosis factor alpha and interleukin 1beta produced a dose-dependent increase in
      IL-8 production. The increase with all three was significantly reduced by the
      tyrosine kinase inhibitors herbimycin A and genistein. Activation of PKC by
      phorbol myristate acetate was also an effective stimulus to IL-8 production and
      this was blocked by PKC depletion or inhibitors. Protein kinase C inhibition did
      not reduce the stimulation produced by H. pylori or the cytokines. Stimulation of
      PKA with forskolin or dibutyryl cyclic adenosine monophosphate or inhibition with
      H89 had no effect on IL-8 production. The calcium ionophore A23187 was a weak,
      PKC dependent, stimulant of IL-8 production. The production of IL-8 in AGS cells
      is stimulated via tyrosine kinase and protein kinase C dependent pathways.
      Stimulation by H. pylori, tumour necrosis factor alpha and interleukin 1beta
      requires tyrosine kinase activity.

PMID- 9237815
TI  - Migration responses of human monocytic cell lines to alpha- and beta-chemokines.
AB  - The beta-chemokines monocyte chemotactic protein 1 (MCP-1), macrophage
      inflammatory protein 1 alpha (MIP-1alpha), MIP-1beta and regulated on activation,
      normal T cells, expressed and secreted (RANTES) induced the in vitro migration of
      the monocytic cell line MonoMac-6. MCP-1 exhibits the most potent chemotactic
      effect on this cell line while MIP-1alpha, RANTES and to a lesser extent MIP
      1beta were more moderate inducers of cell migration. MonoMac-6 migration in
      response to chemokines was shown to be a chemotactic and not a chemokinetic
      response, which was inhibited by pertussis and cholera toxins suggesting a role
      for G proteins in chemokine receptor-mediated signalling in these cells;
      chemotaxis of MonoMac-6 cells in response to MCP-1 was abrogated by the addition
      of anti-MCP-1 antibody. The response of MonoMac-6 cells to the alpha-chemokines
      IL-8, IP-10, growth-related peptide (Gro) alpha and MIP-2beta was substantially
      weaker than to the beta-chemokines. MCP-1 caused an alteration in cellular
      morphology by increasing ruffling at the cell membrane and the number of cells
      exhibiting extended pseudopodia. The chemotactic response of MonoMac-6 cells to
      beta-chemokines was compared with less well-differentiated myelomonocytic cell
      lines. THP-1 showed a similar, but weaker response to the beta-chemokines while
      both HL60 and U937 failed to respond to any member of this subfamily when tested
      under the same conditions. These results suggest that the differentiation status
      of cells of monocytic lineage may affect their response to beta-chemokines.

PMID- 9237816
TI  - The assay of interleukin 4 in the serum of normal subjects and atopic patients
      using a novel immunoassay.
AB  - Interleukin 4 (IL-4) was measured in the serum of normals and mild atopic
      patients using a high sensitivity ELISA system involving an amplification stage.
      The method was found to have a limit of detection of 0.02 pg/ml after a square
      root transformation of the concentration data and to show good reproducibility
      with coefficients of variation between 11 and 14%. Recoveries of standard IL-4
      from serum was greater than 90%. Markedly elevated levels of IL-4 were seen in
      the atopic groups compared with the normals. No association was found between
      total white cell counts, lymphocyte or eosinophil counts and serum IL-4 levels.
      This study demonstrates that serum IL-4 levels can distinguish between atopic
      subjects and normals, even in mild or symptomless disease. This may prove
      valuable in the management of atopic disorders.

PMID- 9237829
TI  - Changes in Achievement Goal Orientations, Perceived Academic Competence, and
      Grades across the Transition to Middle-Level Schools
AB  - Goal orientation theory was used to examine changes in student motivation during
      the transition from elementary to middle school. Surveys were given to 341
      students in the fifth grade in elementary and again in sixth grade in middle
      school. Students were more oriented to task goals (wanting to improve their
      competency), perceived a greater emphasis on task goals during instruction, and
      felt more academically competent in fifth grade in elementary school than in
      sixth grade in middle school. They perceived a greater emphasis on performance
      goals (an emphasis on relative ability and right answers) in middle school than
      in elementary school. Several interactions emerged between year (fifth grade,
      sixth grade), and both student level of ability (higher, lower, based on
      standardized achievement tests) and subject domain (math, English).

PMID- 9237830
TI  - Effects of Three Types of Elaboration on Learning Concepts from Text
AB  - Two experiments were performed to evaluate the effects of three different
      elaborative activities on concept learning. Experiment 1 consisted of 60
      undergraduates, while Experiment 2 consisted of 54 undergraduates. In both
      experiments, subjects studied a passage which asked them to create personal
      examples of the target concepts, contrast the target concepts, or expand on the
      effects of the target concepts. Subjects took a criterion test which consisted of
      recall of concept definitions and teaching examples, classification of novel
      examples, and problem solving scenarios. In both experiments, the condition which
      asked subjects to contrast the target concepts produced significantly better
      performance than the other two conditions. Possible explanations focus on: (1)
      the degree to which the different elaborative activities influence the richness
      and/or distinctiveness of the encoded information, and (2) the relation among the
      focus of the elaborative activity, the experimental text, and the measured
      criterion outcomes.

PMID- 9237831
TI  - Spatial-Semantic Display Processing: The Role of Spatial Structure on Recall
AB  - The purpose of the present study was to test a model of spatial-semantic display
      processing by comparing the aided and unaided recall of information presented in
      a node-link format (knowledge map) to the aided and unaided recall of information
      presented in a text format. Structural icons of the knowledge map and text with
      the verbiage removed were used to aid retrieval in some conditions. Participants
      were randomly assigned to one of eight groups formed by the complete crossing of
      three factors: knowledge map versus text, structural icon at recall versus no
      structural icon at recall, and immediate versus delayed recall. Knowledge map
      groups outperformed text groups on essay tests and they more accurately
      remembered where information was located within the materials. Both knowledge map
      and text icon-aided recall groups had significantly better performance than the
      no icon, unaided recall groups (particularly on main ideas).

PMID- 9237832
TI  - Interventions in Children's Deductive Reasoning with Indeterminate Problems
AB  - This study examined the effectiveness of three intervention measures designed to
      facilitate 10- and 12-year-old children's recognition of indeterminacy in
      reasoning with illogical syllogisms. The indeterminate nature of these syllogisms
      arises from the lack of logical connection between the premises, which means a
      single, logically correct solution cannot be drawn. The interventions addressed:
      (a) children's purported difficulties with closure, specifically, a lack of
      awareness and acceptability of indeterminate situations; (b) children's
      construction of complete mental models of the premise information; and (c) a
      combined approach, incorporating (a) and (b). The children brought a strong
      foundation of deductive processes to the study, which was necessary, but
      insufficient, for dealing with the indeterminate problems. Neither intervention
      (a) nor (b) alone, was adequate in developing children's ability to explicitly
      recognize indeterminacy; only the combined intervention made a significant
      difference. Possible reasons for this are explored, along with an analysis of
      children's difficulties in resolving these problems. A number of educational
      implications are also addressed.

PMID- 9237833
TI  - Item-Specific Efficacy Judgments in Mathematical Problem Solving: The Downside of
      Standing Too Close to Trees in a Forest
AB  - Educational researchers assess self-efficacy by asking students to rate their
      capability of succeeding at specific target tasks (e.g., math test items) and
      then testing their performance to actually solve similar test items. Pajares and
      colleagues (Pajares & Kranzler, 1995; Pajares & Miller, 1994, 1995, in press)
      argued for the use of identical items to assess self-efficacy and performance in
      order to maximize self-efficacy's predictive power. In two studies, structural
      equation models (SEM) demonstrated that this variation led to positively biased
      estimates of paths from self-efficacy to performance and negatively biased
      estimates of paths from self-concept to performance. Whereas corrections for this
      bias did not substantially alter the size of effects or substantive
      interpretations, results from both studies were consistent with a priori
      predictions about the nature of this bias. Researchers are encouraged to use
      similar but not identical items to assess self-efficacy and performance, a
      construct validity approach to interrogate their interpretations, more diverse
      outcome measures, and SEM approaches like those demonstrated here.

PMID- 9237834
TI  - Reexamining the Relationship between Verbal Knowledge Background and Keyword
      Training for Vocabulary Acquisition
AB  - The literature on keyword training presents a confusing picture of the usefulness
      of the keyword method for foreign language vocabulary learning by students with
      strong verbal knowledge backgrounds. This paper reviews research which notes the
      existence of conflicting sets of findings concerning the verbal background
      keyword training relationship and presents the results of analyses which argue
      against the assertion made by McDaniel and Pressley (1984) that keyword training
      will have minimal effect on students with high verbal ability. Findings from
      regression analyses of data from two studies did not show that the relationship
      between keyword training and immediate recall performance was moderated by verbal
      knowledge background. The disparate sets of findings related to the keyword
      training-verbal knowledge relationship and themes emerging from other research
      suggest that this relationship requires further examination.

PMID- 9237835
TI  - Effect of Topic Frequency and Position on Memory for Information from Lengthy
      Informative Text
AB  - In this study we explore two aspects of text that have a theoretical basis for
      providing a cue to readers as to the likelihood that a particular concept is an
      important topic within a passage. College students read one of two versions of a
      chapter length passage in which we manipulated both the frequency of mention of a
      topic label and the position in the passage where the topic is first mentioned.
      The effects of these frequency and position manipulations were measured on both
      recognition memory and recall. Neither frequency nor position had an effect on
      recognition of important passage concepts. Position had no effect on recall as
      well but high frequency increased the likelihood that a topic would be recalled.
      These results are consistent with any of several models of comprehension which
      view strength of a memory trace as dependent on frequency of activation.
      Implications of these findings for instruction are discussed.

PMID- 9237836
TI  - The Face-Name Mnemonic Strategy from a Different Perspective
AB  - Prior research has demonstrated that the face-name mnemonic strategy is useful
      for facilitating memory for names in response to true-to-life representations of
      faces (e.g., photographs). In Experiment 1, we successfully extended this finding
      to a situation in which the stimuli cuing name memory were caricatures. In
      Experiment 2, photographs and caricatures alternated as the stimulus materials
      prompting either name recall or recognition. Students using the mnemonic strategy
      again outperformed students using their own best method of study on both
      immediate and delayed tests. Because caricatures exaggerate prominent features,
      we had anticipated that the mnemonic approach might be relatively more effective
      with caricatures than with photographs. However, students using the face-name
      mnemonic strategy derived comparable benefits with both types of material.

PMID- 9237858
TI  - Description and function of the ciliary nerves--some historical remarks on
      choroidal innervation.
AB  - The earliest accounts of the eye recognized its main function as providing
      vision, but the mechanism of how the eye functioned remained obscure for many
      centuries. The aim of the following work is to outline these changes in the
      understanding of a particular structure and function of the human body, namely,
      the ciliary nerves supplying the uveoscleral part of the eye. In the extensive
      study on the history of ophthalmology by Hirschberg (published between 1899 and
      1918), the ciliary nerves and choroidal innervation are only sparsely mentioned.

PMID- 9237859
TI  - Lysophosphatidic acid stimulates two ion currents in cultured human retinal
      pigment epithelial cells.
AB  - Lysophosphatidic acid (LPA) is a simple phospholipid that can be released from
      thrombin-activated platelets and growth factor-activated fibroblasts. The effects
      of this lipid signaling molecule on membrane currents of cultured human retinal
      pigment epithelial (RPE) cells were investigated using whole cell recording
      techniques. Bath application of LPA evoked an inward current that was sometimes
      preceded by an outward current. The inward current reversed near 0 mV regardless
      of Cl- equilibrium potential and was suppressed by lowering extracellular [Na+]
      or application of Cd2+ (3 mM) suggesting that it is a non-selective cation
      current. The outward current reversed near the K+ equilibrium potential (EK)
      suggesting it is carried predominantly by K+ ions. The effects of LPA appear to
      be mediated by a receptor rather than non-specific detergent effects since: (a)
      both currents showed a similar saturating concentration/response relationship;
      (b) lysophosphatidylcholine, which has the same lipid tail as LPA, was
      significantly less effective than LPA in evoking inward currents; (c) LPA-evoked
      currents diminished with repeated applications of LPA suggesting receptor
      desensitization or washout of second messenger systems during whole cell
      recording; and (d) pertussis and cholera toxin pre-treatment suppressed the
      inward current, although not the outward current. Bath application of a calcium
      ionophore, ionomycin, stimulated an outward current which, like the LPA-sensitive
      current, reversed near EK. The results suggest that LPA stimulates one or more
      receptor subtypes which can associate with both a pertussis toxin-sensitive G
      protein resulting in generation of an inward cation current and a pertussis toxin
      insensitive G protein resulting in generation of an outward current carried
      predominantly by K+.

PMID- 9237860
TI  - Calcium-mediated neurofilament protein degradation in rat optic nerve in vitro:
      activity and autolysis of calpain proenzyme.
AB  - In this study, we examined calcium-mediated degradation of a neurofilament
      protein (NFP), and autolytic activation of calpain in Lewis rat optic nerve in
      vitro. After incubation with calcium, homogenized optic nerve samples were
      analysed by SDS-PAGE in association with ECL immunoblot techniques. 68 kD NFP,
      calpain, and calpastatin antibodies were used for identification of the
      respective proteins. The extent of calcium-mediated 68 kD NFP degradation
      compared to EGTA controls, served to quantify calpain activity, while the extent
      of calpain autolysis measured the activation of the enzyme. A progressive loss of
      68 kD NFP was observed at 15 min (42.1%), 1 hr (52.7%) and 6 hr (73.4%)
      incubation periods compared to EGTA controls. The immunoreactive calpain bands
      showed progressive autolysis after 15 min (26.6%), 1 hr (31.4%) and 6 hr (43.4%)
      incubations. We also found degradation of low molecular weight isoforms of
      calpastatin (43 kD and 27 kD) in the presence of calcium compared to controls.
      These results indicate that calpain is present in optic nerve in its inactive
      form but when calcium is added, it undergoes autolysis and becomes active. Thus,
      active calpain is capable of degrading endogenous substrates (e.g. cytoskeletal
      and myelin proteins) and may promote the degeneration of optic nerve in optic
      neuritis.

PMID- 9237861
TI  - Iris pigment epithelial cells of long evans rats demonstrate phagocytic activity.
AB  - The phagocytic activities of iris pigment epithelial (IPE) cells and retinal
      pigment epithelial (RPE) cells of Long Evans rats towards latex beads and rod
      outer segments (ROS) were compared in vitro. IPE and RPE cells of Long Evans rats
      were isolated and pure cultures obtained. The cultures were incubated with latex
      beads, fixed, and analysed computer morphometrically, IPE and RPE cell cultures
      were also incubated with isolated ROS and examined using transmission electron
      microscopy. IPE cells were able to ingest latex beads. There was no significant
      difference between the number of latex particles phagocytized by IPE and RPE
      cells. After incubation with isolated ROS, IPE cells also recognized and ingested
      the ROS particles. However, the specific phagocytic capacity of IPE cells was 76%
      of that of RPE cells. The autologous IPE cells might have the potential to be
      used as an alternative to RPE cells for transplantation in the subretinal space.

PMID- 9237862
TI  - Superior cervical ganglionectomy in monkeys: light and electron microscopy of the
      anterior eye segment.
AB  - Morphological changes in the anterior eye segment of eight cynomolgus monkeys
      were investigated 2 days to 2.2 years after unilateral surgical superior cervical
      ganglionectomy (SCGx). SCGx was confirmed by histologic examination of the
      excised surgical specimen and persistent ipsilateral miosis. In four short-term
      monkeys (2, 4, 7 and 11 days), iris, ciliary muscle and trabecular meshwork were
      studied by electron microscopy. In the other four longer-term monkeys (3 week, 4
      week, 5 week, 2.2 year) the anterior eye segment was investigated with tyrosine
      hydroxylase immunohistochemistry (TH-IR) and catecholamine fluorescence (CF).
      Electron microscopy of experimental eyes showed characteristic signs of Wallerian
      degeneration in numerous nerve fibers and terminals in the iris, but to a lesser
      extent in the ciliary muscle and the trabecular meshwork. TH-IR and CF showed
      marked interindividual differences. In all experimental eyes, there was a marked
      reduction, but never a complete absence of adrenergic nerves in the iris. In two
      animals (4 week and 2.2 years), the adrenergic innervation of the ciliary body
      and the chamber angle was similarly reduced. In contrast, in the experimental
      eyes of the other two animals (3 and 5 weeks), changes in adrenergic innervation
      to the ciliary body and chamber angle were minimal or absent. The results
      indicate that following apparently complete SCGx in the cynomolgus monkey,
      reduction of adrenergic innervation to the iris as evidenced by pupillary
      physiology, electron microscopy, TH-IR and CF does not guarantee reduction in
      adrenergic innervation to the ciliary body and trabecular meshwork. SCGx may not
      extirpate all third order sympathetic neurons in the distal stump, or there may
      be a significant contribution of accessory ganglion cells to the adrenergic
      innervation of the anterior eye segment.

PMID- 9237863
TI  - Variability in rate of cone degeneration in the retinal degeneration (rd/rd)
      mouse.
AB  - The retinas of rd/rd mice with inherited retinal degeneration were examined
      histologically at postnatal days 60-66, an age when most rod cells already have
      degenerated and disappeared but when a significant number of cones are still
      present. We observed an unexpected hemispheric asymmetry and large variability in
      the number of surviving cones. Significantly more cones survived in the inferior
      than in the superior hemisphere in most retinas, although in about 15% of animals
      the hemispheric asymmetry was absent or was reversed. The number of surviving
      cones was highly variable from animal to animal, ranging from 3-30, a factor of
      10, within the superior hemisphere, and from 7-51, a factor greater than 7, in
      the inferior hemisphere. If the specific hemisphere was ignored, the number
      ranged from 3-51, a factor of 17. These findings have significance for the
      examination of cone survival in the late stages of degeneration in this widely
      studied mutant, including therapeutic studies using transplantation, gene therapy
      or survival factors, as well as for the identification of surviving cells using
      cone-specific markers.

PMID- 9237864
TI  - Electron microscopic immunohistochemistry of ocular and extraocular
      pseudoexfoliative material.
AB  - To investigate the nature of extraocular pseudoexfoliative (PSX) material, and to
      validate the hypothesis that the PSX syndrome is a systemic disorder, we studied
      the immunoreactivity of intraocular and extraocular PSX material from patients
      with the PSX syndrome using antibodies against proteins of extracellular
      matrices. Surgical specimens of four different tissues were obtained from human
      eyes with the PSX syndrome: nine trabecular tissues, three cataractous lenses,
      six bulbar conjunctivas, and seven lid skins. These tissues were processed for
      electron microscopic immunohistochemistry, and stained with antibodies against
      vitronectin, fibronectin, laminin, and elastin, by an indirect immunogold
      procedure. Density of the gold particles located on the PSX material was
      estimated by video image analysis. Statistical analysis of the data revealed that
      the PSX material from trabecular tissues, lenses, bulbar conjunctivas, and lid
      skins had almost identical immunoreactivity to the antibodies studied. PSX
      materials of trabecular tissues, lenses, bulbar conjunctivas, and lid skins were
      found to have not only a similar ultrastructure, but also almost identical
      immunohistochemical characteristics. These results support the hypothesis that
      the PSX syndrome is a systemic disorder.

PMID- 9237865
TI  - A one year study of the macular pigment: the effect of 140 days of a lutein
      supplement.
AB  - A low density of macular pigment may represent a risk factor for age-related
      macular degeneration (AMD) by permitting greater blue light damage. This study
      was carried out to determine the effects on macular pigment optical density of
      dietary supplementation with lutein, one of the pigment constituents. Two
      subjects consumed lutein esters, equivalent to 30 mg of free lutein per day, for
      a period of 140 days. Macular pigment optical density was determined by
      heterochromatic flicker photometry before, during, and after the supplementation
      period. Serum lutein concentration was also obtained through the analysis of
      blood samples by high-performance liquid chromatography. Twenty to 40 days after
      the subjects commenced taking the lutein supplement, their macular pigment
      optical density began to increase uniformly at an average rate of 1.13+/-0.12
      milliabsorbance units/day. During this same period, the serum concentration of
      lutein increased roughly tenfold, approaching a steady state plateau. The optical
      density curve eventually levelled off 40 to 50 days after the subjects
      discontinued the supplement. During the same 40 to 50 days, the serum
      concentration returned to baseline. Thereafter, little or no decrease in optical
      density was observed. The mean increases in the macular pigment optical density
      were 39% and 21% in the eyes of the two subjects respectively. In conclusion, the
      modest period of supplementation has been estimated to have produced in the
      subjects a 30 to 40% reduction in blue light reaching the photoreceptors, Bruch's
      membrane, and the retinal pigment epithelium, the vulnerable tissues affected by
      AMD.

PMID- 9237866
TI  - Posttranscriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase
      in lens epithelial cells by mevalonate-derived nonsterols.
AB  - The ocular lens must continuously synthesize the cholesterol required to support
      membrane formation for its life-long growth. The roles of transcriptional and
      posttranscriptional mechanisms in controlling 3-hydroxy-3-methylglutaryl coenzyme
      A reductase (HMGR) protein levels in cultured lens epithelial cells were examined
      by measuring the effect of restricting exogenous cholesterol, endogenous
      cholesterol synthesis and mevalonate derived nonsterols upon HMGR protein and
      mRNA levels and upon the synthesis and degradation of HMGR protein. Sterols were
      restricted by culturing in lipoprotein deficient media and blocking 2,3
      oxidosqualene cyclase with U18666A. Mevalonate derived nonsterols were
      additionally restricted by inhibition of HMGR activity with lovastatin. A 4-fold
      increase in HMGR protein levels due to restricting sterols with U18666A could be
      explained by comparably increased mRNA levels and enzyme protein synthesis. The
      very rapid turnover of HMGR protein (T(1/2) approximately 45 min) was unaffected.
      The additional restriction of mevalonate derived nonsterols increased HMGR
      protein levels to about 400-fold. A 10-fold slowing in the rate of enzyme
      degradation coupled with at least a 5-fold increase in mRNA levels likely
      accounted for this accumulated protein mass. The capacity of the nonsterol
      regulators to promote enzyme degradation appeared independent of sterols, since
      mevalonate restored rapid degradation of HMGR protein when 2,3-oxidosqualene
      cyclase activity was simultaneously blocked. Thus, in cultured lens epithelial
      cells, sterols appear to exert a modest influence on HMGR protein levels solely
      by suppressing transcription; whereas, mevalonate derived nonsterols exert major
      influence mainly by accelerating enzyme protein degradation. We speculate that
      nonsterol isoprenes might be important for preventing overexpression of
      cholesterol biosynthesis in the intact lens.

PMID- 9237867
TI  - Endothelin-1 stimulates the release of arachidonic acid and prostaglandins in
      cultured human ciliary muscle cells: activation of phospholipase A2.
AB  - In the present study we have examined the effects and mechanisms of endothelin-1
      (ET-1) on arachidonic acid (AA) release and prostaglandin (PG) synthesis in human
      ciliary muscle (HCM) cells. ET-1 stimulated AA release in a time (t1/2=1.5 min)
      and concentration-dependent (EC50=5 nM) manner, which is primarily mediated
      through the ETA receptor subtype. The AA liberated by ET-1 appears to derive
      mainly from the phosphoinositides and phosphatidylcholine. Our data show that
      phospholipase A2 (PLA2), but not phospholipase C (PLC), plays an important role
      in ET-1-induced AA release. This conclusion is supported by the following
      findings: (1) ET-1-evoked AA release was inhibited by the PLA2 inhibitors
      dexamethasone, mepacrine and manoalide in a concentration-dependent manner.
      Conversion of AA into PGE2 was inhibited by the cyclooxygenase inhibitors in the
      following order: Indomethacin>naproxen >ibuprofen>NS-398>aspirin. (2) The phorbol
      ester, PDBu, an activator of protein kinase C, potentiated ET-1-induced AA
      release by 39%, but inhibited that of inositol phosphates formation by 62%. (3)
      Pretreatment of the labeled cells with isoproterenol lowered ET-1-induced
      inositol phosphates production, but had no effect on AA release. (4) U71322, a
      PLC inhibitor, inhibited ET-1-induced inositol phosphates production, but had no
      effect on that of AA release. (5) Pretreatment of the cells with pertussis toxin
      (0.1 microg ml-1) attenuated the stimulatory effects of ET-1 on AA release and
      PGE2 formation. These data demonstrate that ET-1 is a potent agonist for AA
      release and PG synthesis in HCM cells, and that PLA2, but not PLC, plays an
      important role in ET-1-induced AA release and PG synthesis. In ciliary muscle, AA
      and its metabolites play important roles in intracellular signalling, modulation
      of physiological processes, and regulation of intraocular pressure.

PMID- 9237868
TI  - Calcium and its localization in human lens fibres: an electron tomographic study.
AB  - The ultrastructural distribution of calcium was studied in human lens fibres with
      the oxalate pyroantimonate technique. In the intermediate cortex precipitates
      were found perimembranous and occasionally in the fibre cytoplasm. The improved
      resolution of electron tomography revealed (a) that the perimembranous
      precipitates as described earlier by Vrensen et al. (1995) are restricted to the
      intercellular space; no indications were found of an increased intracellular
      submembranous calcium level, and (b) the existence of an intracellular pool of
      small protein attached precipitates in the fibre cytoplasm not observed with
      conventional electron microscopy. It is concluded that in the intermediate and
      deep cortex, where in the mature fibres all cellular calcium pools have
      disappeared, two calcium pools exist: (a) a pool of free calcium ionically bound
      to the negatively charged phospholipids of the external face of the fibre
      membrane and (b) a cytoplasmic pool of protein associated calcium. Possible
      candidates for this cytoplasmic calcium binding are discussed.

PMID- 9237869
TI  - Specific immunosuppression of corneal allograft rejection by combination of anti
      VLA-4 and anti-LFA-1 monoclonal antibodies in mice.
AB  - It has been reported that allograft rejection is mediated by a variety of
      adhesion molecules. Using a corneal allograft model in mice, we studied the role
      of very late antigen (VLA)-4 and leukocyte function-associated antigen (LFA)-1
      adhesion molecules in corneal allograft rejection and the effects of monoclonal
      antibodies (mAbs) to them in suppressing corneal rejection. C3H/He donor corneas
      were transplanted into BALB/c corneal beds. The allografted mice were treated
      with a control mAb (M18/2), mAbs to VLA-4, or LFA-1 or their combination by i.p.
      injection until day 7. The expression of VLA-4, LFA-1, major histocompatibility
      complex (MHC) class II antigens, interleukin (IL)-2, IL-2 receptor and interferon
      gamma (IFNgamma) in the grafted cornea were studied immunohistochemically.
      Cytotoxic T lymphocyte (CTL) responses to donor alloantigens were assessed. The
      skins from a syngeneic donor or a third-part strain were transplanted 8 weeks
      after the initial keratoplasty onto the mice treated with anti-LFA-1 plus anti
      VLA-4 mAbs. Fourteen of 16 allografts in non-treated mice and control mAb-treated
      mice became opaque by 2 weeks after transplantation. At 2 weeks, non-treated
      allografts showed expression of MHC class II antigens on keratocytes and
      mononuclear cells at the host-graft junction. Also, mononuclear cells expressing
      VLA-4, LFA-1, IL-2, IL-2 receptor and IFNgammawere present in the stroma at the
      host-graft junction. The allografts treated with either anti-VLA-4 or anti-LFA-1
      alone, or anti-VLA-4 plus anti-LFA-1 remained transparent for more than 2 weeks,
      and the survival rates at 14 weeks was 0%, 16.7%, and 75.0%, respectively. The
      combined use of anti-VLA-4 and anti-LFA-1 mAbs prolonged graft survival
      significantly (P<0.05) at 14 weeks as compared with anti-LFA-1 mAb alone. At 3
      weeks, CTL responses to donor alloantigens were depressed in mice treated with
      either anti-LFA-1 alone or anti-LFA-1 plus anti-VLA-4. Specific prolongation of
      donor-syngeneic skin was observed after treatment with the combination of these
      two mAbs. These results indicate that VLA-4 and LFA-1 have important roles in
      rejection process of corneal allografts, and that the combined use of mAbs to
      these molecules has remarkable effects on inducing alloantigen-specific
      immunosuppression in corneal transplantation.

PMID- 9237870
TI  - Specific racemization and isomerization of the aspartyl residue of alphaA
      crystallin due to UV-B irradiation.
AB  - We have reported that the aspartyl (Asp)-151 residue in alphaA-crystallin in
      human eye lens was inverted to the D-isomer and isomerized to beta-Asp residue
      with age. We report here that ultraviolet (UV)-B irradiation induces the
      racemization and isomerization of the Asp-151 residue of alphaA-crystallin from
      lenses of 6-week-old rats to form D-isomer and beta-Asp residue. Simultaneous
      racemization and isomerization of the specific Asp residue indicate that the
      reaction proceeds via formation of a succinimide intermediate. This modification
      was not observed in UV-A irradiated and normal lenses. UV-B irradiation induced
      the racemization of only the Asp-151 residue and did not affect the other Asp
      residues in alphaA-crystallin. On the other hand, the high molecular weight
      fraction of the lens protein increased upon UV-B irradiation. Modification of the
      Asp residue would affect the three-dimensional packing array of the lens protein.

PMID- 9237871
TI  - Morphologic evidence for a preferential storage of tissue plasminogen activator
      (t-PA) in perivascular axons of the rat uvea.
AB  - The uveal layer is thought to hold the largest stores of tissue plasminogen
      activator (t-PA) within the eye. However, the uveal cell types that contain and
      could release t-PA to contiguous tissues and fluids have not been clearly
      identified. In the present study the general distribution pattern of t-PA antigen
      in fresh rat iris and choroid tissue was determined by immunofluorescence in
      preliminary light microscopic (LM) cryosections. Transmission electron
      microscopic (TEM) immunogold localization was then used to detect specific
      cellular and subcellular sites of t-PA antigen. The primary antibody was rabbit
      anti-mouse t-PA IgG. The immunofluorescence in preliminary LM cryosections of
      both tissues was most intense over discrete linear and cross-sectioned structures
      that resembled the contours of axon bundles. This impression was strengthened
      when silver impregnation highlighted similar structures in separate sections of
      the same tissue samples. TEM immunogold labeling of thin sections then confirmed
      that the t-PA antigen was confined to the axoplasm of both myelinated and
      unmyelinated perivascular nerve fibers in both the iris and choroid. Gold
      particles were not observed over axonal membranes, myelin sheaths, Schwann cells,
      retinal pigment epithelium or vascular endothelial cells. Ultrathin TEM
      cryosections of the iris showed a localization of some particles over structures
      that resembled tubules and vesicles within the axoplasm, but not over
      mitochondria. The axonal location of t-PA was shown by the co-localization of t
      PA with an antibody against rat neurofilaments. The typical axon morphology that
      enclosed the t-PA particle markers in all TEM sections also indicated an axonal
      location. Separate TEM sections were processed with conventional fixatives and
      stains to highlight the typical uveal axon morphology, which also confirmed the
      identity of perivascular axons as the sites of t-PA localization. Affinity of the
      primary antibody for rat t-PA was shown by an inhibition ELISA against rat uveal
      tissue extracts and by the inhibition of t-PA activity in aqueous humor. An
      amidolytic assay was used to quantify t-PA activity. Possible explanations for
      the preferential immunolocalization of t-PA antigen to the axoplasm of uveal
      nerve terminals and the need for additional functional studies to confirm a
      putative neural t-PA synthesis are discussed.

PMID- 9237872
TI  - Extracellular matrix of retinal pigment epithelium regulates choriocapillaris
      endothelial survival in vitro.
AB  - The role of extracellular matrix of retinal pigment epithelial cells (RPE-ECM) in
      the regulation of the survival of choriocapillaris endothelial cells (CCE) was
      investigated in vitro. The CCE survival was evaluated by trypan blue staining,
      neutral red uptake, and the counting of viable cells. Results showed that CCE
      cells survived on RPE-ECM. Pre-treatment of RPE-ECM individually with
      neutralizing antibodies to acidic fibroblast growth factor, vascular endothelial
      growth factor, platelet-derived growth factor, or transforming growth factor
      beta(pan specific to TGFbeta1, TGFbeta1.2, TGFbeta2 and TGFbeta5), did not alter
      the survival rate of CCE cells on RPE-ECM, as compared to that of the control
      (CCE survival rates on RPE-ECM pretreated with normal rabbit IgG). However, the
      treatment of RPE-ECM with neutralizing antibody to basic fibroblast growth factor
      (bFGF) caused CCE death by 77.1+/-15.7%. The CCE death was defined as apoptosis
      based on the morphological markers (shrinkage in cell size with blebbing of
      plasma membranes, condensation and fragmentation of nuclei, and DNA fragmentation
      in multiples of approximately 200 bp). The addition of phorbol 12-myristate 13
      acetate (PMA) (2 nM) to the culture medium was effective for complete prevention
      of CCE apoptosis; the protecting effect of PMA on CCE apoptosis can be abolished
      by H7 (25 microM), but not HA1004 (50 microM), suggesting the involvement of PKC
      in protecting CCE from apoptosis. The inhibition of protein synthesis of CCE
      cells by cycloheximide (0.1 microM) did not affect the apoptotic process of the
      cells. In a separate experiment, when CCE cells were cultured in a medium
      saturated with bFGF (5 ng ml-1) without RPE-ECM, the cells also died by
      apoptosis. However, this apoptotic process was not affected by PMA. Cycloheximide
      also failed to affect the apoptotic process. These results suggest that both RPE
      ECM insoluble molecules and RPE-ECM-bound bFGF modulate choriocapillaris survival
      by suppressing CCE apoptosis.

PMID- 9237873
TI  - In vitro hydration kinetics of recent post-mortem tissue versus pre-dried corneal
      stromal tissue.
AB  - Both recent post-mortem and pre-dried corneal tissue has been used for laboratory
      studies of stromal swelling, but it has yet to be defined whether the same
      hydration (H value, mg H2O/mg dry mass) is obtained after extended re-hydration.
      Fresh or pre-dried pieces (8x8 mm squares) of ovine stromas were immersed in 1%
      NaCl for 24 hr at 37 degrees C, with the wet mass assessed regularly. Pre-drying
      was achieved in air for 7 days (with sulphuric acid, CaSO4 or silica gel as
      desiccants), or in an oven for 24 hr at 60, 70 or 80 degrees C. Fresh stroma
      preparations (</=2 hr post-mortem) had initial H values of 3.1, which increased
      to 27.8 after 24 hr in saline. After pre-drying over sulphuric acid, CaSO4 or
      silica gel, the H values after 24 hr in saline were 19.1, 13.1 and 7.3
      respectively (all statistically different from fresh tissue (P<0.01). Following
      oven drying at 60, 70, and 80 degrees C, final H values of 8.5, 6.6, and 5.0 were
      obtained after 24 hr in saline. Recent post-mortem material showed sustained
      swelling over at least 24 hr. For pre-dried tissue, initial rates of hydration
      change over 1 hr were higher, but subsequent rates were substantially less after
      2 hr. These studies indicate that fresh tissue should be used in studies
      concerning the swelling properties of the corneal stroma.

PMID- 9237874
TI  - Fuchs' corneal endothelial cells transduced with the human papilloma virus E6/E7
      oncogenes.
AB  - We sought to develop corneal endothelial cell cultures with extended lifespan
      from corneas with Fuchs' dystrophy. Descemet's-endothelial cell explants from
      histology confirmed recipient corneas of two patients with Fuchs' dystrophy were
      cultured. After a small number of corneal endothelial cells with irregular,
      endothelial morphology migrated from the explants onto the culture plate, the
      cells were transduced with a disabled retrovirus (pLXSN16E6/E7) coding for the
      human papilloma virus type 16 transforming oncoproteins E6 and E7. Expression of
      E6/E7 mRNA in the cell cultures with extended lifespan was monitored by RT-PCR.
      In vitro labeled cellular protein patterns of the Fuchs' E6/E7 cell cultures with
      extended lifespan were compared with those from normal human corneal endothelial
      E6/E7 cell cultures with extended lifespan using two-dimensional gel
      electrophoresis. Two endothelial cell cultures with extended lifespan were
      derived from Fuchs' corneas. The morphology of the Fuchs' cells expressing E6 and
      E7 was similar to that of normal corneal endothelial cells expressing E6 and E7.
      Surprisingly, the rate of proliferation of Fuchs'-derived cells was similar to
      that of normal endothelial cells transduced with E6/E7. Proliferation of each
      Fuchs' cell culture with extended lifespan continued for over 30 population
      doublings. There were limited quantitative differences in the two-dimensional gel
      electrophoretic protein patterns of the Fuchs'-derived and normal endothelial
      cell cultures with extended lifespan, respectively. Retroviral integration is
      dependent on cell proliferation. Thus, cells that migrated from the Fuchs'
      Descemet's explants were undergoing at least limited in vitro proliferation when
      the retroviral vector coding for E6/E7 integrated. Fuchs' corneal endothelial
      cells expressing E6 and E7 had similar proliferation, cellular morphology, and
      two-dimensional gel protein electrophoretic patterns to normal corneal
      endothelial cells expressing the same oncoproteins.

PMID- 9237875
TI  - New non-contact specular microscope for lens epithelial cell visualization.

PMID- 9237883
TI  - Interleukin-10 prevents early cytokine release in severe intraabdominal infection
      and sepsis.
AB  - Early release of macrophage-derived proinflammatory cytokines, such as tumor
      necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the
      pathogenesis of septic shock and multisystem organ failure in various models of
      sepsis. IL-10 is a mediator that inhibits cytokine release from activated
      macrophages. The aim of this study was to determine if IL-10 would decrease serum
      cytokine elevation in a murine model of cecal ligation and puncture (CLP). CLP in
      animals is a model that closely mimics the physiologic changes seen in human
      sepsis. Four groups of 14 female Swiss-Webster mice were used. Group 1 underwent
      laparotomy alone, groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2
      received intraperitoneal (IP) saline injections to serve as control vehicle.
      Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3
      hr thereafter. Group 4 (therapeutic) received 10,000 U IP IL-10 1 hr following
      CLP and every 3 hr thereafter. Animals were sacrificed at 3 and 9 hr following
      CLP. Serum TNF-alpha, IL-1 beta, and IL-6 were determined by enzyme-linked
      immunosorbent assay (ELISA), CLP produced a significant rise in serum TNF,IL-6,
      and IL-1 in untreated controls. Prophylactic or therapeutic administration of IL
      10 significantly attenuated this early rise in serum cytokines. These results
      support the hypothesis that (1) CLP produces an early systemic rise in macrophage
      derived cytokines and (2) IL-10 given either before or after the onset of CLP
      induced intraabdominal infection and sepsis is able to inhibit this early release
      of macrophage-derived systemic mediators. IL-10 has potential clinical benefits
      in the therapeutic management of intraabdominal infection and sepsis.

PMID- 9237884
TI  - How Do Logical Inference Rules Help Construct Social Mental Models?
AB  - Starting from recent approaches in mental model research, it is argued that (1)
      logical inference rules are used in order to construct mental cliques from
      learned sentiment relations, and (2) social context cues (operationalized as
      primes) play a crucial role in activating such rules. Transitivity and
      antitransitivity are taken as examples, and are shown as core constituents of
      such models. In a first experiment, priming was achieved by announcing the
      sorting of fictitious persons in either two or three cliques. Thirty-one subjects
      studied eight sets of sentiment relations among these persons that either did or
      did not satisfy their primed clique expectations. They showed longer study times
      and more requests for additional information in the case of inconsistent fits
      between prime and set. Their sorting solutions also showed clear priming effects.
      A second experiment (n = 30) showed that when undergoing a recognition test after
      seeing the relation sets, subjects tended to confuse model-consistent distractors
      with information they had actually seen. In a third experiment (n = 30) the
      results from Experiment 1 were replicated using more realistic learning
      materials.

PMID- 9237885
TI  - Anatomical variability and functional ability of vascular trees modeled by
      constrained constructive optimization.
AB  - The aim of this study was to investigate the extent that functional capability of
      vascular trees is related to anatomical variability. To these ends we used the
      method of Constrained Constructive Optimization (CCO) to generate optimized
      computer models of coronary arterial trees. All these model trees were optimized
      according to the same principle under equal boundary conditions of pressures and
      flows. However, by stochastically casting the locations of the terminal segments,
      different tree structures were generated, each of which conformed to the same
      boundary conditions. The structural variability of these models was interpreted
      as the correlate of the anatomical variability found in real arterial trees. The
      advantage that computer model trees are known in numerical detail was exploited
      to perform comprehensive and exact classifications of all segments into
      bifurcation levels, STRAHLER orders and composite vessels, and to compute the
      area expansion ratio. The unexpected result was that, despite striking visual
      differences in anatomical structure, the model trees were almost identical with
      regard to functional performance. We conclude that models optimized on the
      computer for a given perfusion task show little differences in their morphometric
      parameters even if they differ considerably regarding the course of the large
      vessels.

PMID- 9237887
TI  - Genetic code synonym quotas and amino acid complexity: cutting the cost of
      proteins?
AB  - The synonym quotas within the genetic code for the 20 common amino acids are
      examined in relation to the ways in which these amino acids can be marshalled
      into different sets on the basis of shared physico-chemical properties. This
      reveals which shared properties are encouraged or discouraged during the course
      of protein evolution by the arrangement of the code. A dominant theme is that the
      synonym quotas are allocated in favour of small and chemically uncomplicated
      residues, and to the disadvantage of large and chemically prominent ones. From
      amongst the various measurements that can be considered to quantitatively express
      aspects of amino acid residue "size and complexity" (e.g. side chain volume,
      bulkness and formula weight), formula weight has the highest correlation with the
      synonym quota for each amino acid. However, the correlation is weak. A specially
      derived "size/complexity" scale for the amino acids based on their relative
      atomic composition improved the correlation only marginally. The existence of
      another weak correlation between the synonym quotas and the general amino acid
      composition of proteins prompted an investigation of the correlations between
      this composition and the previously considered amino acid properties. Again, the
      highest correlations are with amino acid formula weight and "size/complexity",
      but in this instance the correlations are high enough to be truly significant. It
      is suggested that the biased synonym quotas in the genetic code are intended to
      ensure that proteins as a whole maintain a certain amino acid composition, even
      to the extent that the quotas include compensatory biases to counter opposing
      influences upon this composition caused by the processes of natural selection for
      protein function. It is the need for these compensatory biases that prevents a
      simple correlation between the quotas and measures of amino acid complexity. The
      final outcome, in which amino acids are deployed in functional proteins in
      approximate proportion to their chemical complexity may serve both as a means of
      minimising the negative consequences of random genetic mutation (by reducing the
      chance appearance of the more "disruptive" types of side chain in proteins) and
      as a means of ensuring the most economic use of biosynthetic resources. According
      to this reasoning, the code is not a "frozen accident"; it is universally
      appropriate because it provides the best compromise that can be achieved between
      biosynthetic cost and biological return in respect of the rate of protein
      evolution.

PMID- 9237890
TI  - Use of serum markers to measure acute myocardial infarct size: lessons of a
      nonlinear dynamical model.
AB  - During acute myocardial infarction, dying cells in the myocardium release a
      number of chemicals that appear in the blood stream. By sampling the blood and
      assaying for these markers at intervals after infarction, we obtain a measure of
      the amount of myocardium lost, and the area under the marker concentration curve
      with time has been used to estimate the size of infarct. Because many of the
      important variables in this system are impossible to measure in patients and
      difficult to measure or control in experimental animals, simulations using a
      mathematical model provide an important way to learn about the infarct-marker
      relationship. This paper described a nonlinear dynamical model that allows for
      continuous changes in coronary flow as well as five key parameters during acute
      infarction. These five include amount of marker available for release from the
      myocardium, relative rate of release of marker from the myocardium, rate of
      degradation of marker in the myocardium, plasma volume, and relative rate of loss
      of marker from the plasma. By varying these five together with infarct size,
      simulations using the model demonstrate a noisy relationship between infarct size
      and area under the plasma marker curve. Mathematically, this noise implies that
      there is not a one-to-one mapping from marker curve to infarct size, and we
      should expect no more than a statistical mapping that fails to resolve all the
      uncertainty. The results do suggest that early reperfusion should reduce, rather
      than increase the noise in this relationship.

PMID- 9237893
TI  - Evolutionarily stable strategy distributions for the Repeated Prisoner's Dilemma.
AB  - This paper introduces the idea of an evolutionarily stable strategy distribution,
      which generalizes the idea of an evolutionarily stable strategy; roughly
      speaking, an evolutionarily stable strategy distribution is a finite set of
      symbiotic strategies which is unaffected by low levels of mutation. This idea is
      then applied to the n-person Repeated Prisoner's Dilemma, of which the usual
      Repeated Prisoner's Dilemma is the special case n=2. Given some standard
      assumptions on what mutations are possible, it is shown that if the probability
      of future interactions is sufficiently large, there are no evolutionarily stable
      strategy distributions. (And hence no evolutionarily stable strategies.) An
      example is given of an evolutionarily stable strategy distribution in the case
      when the set of possible mutant strategies is restricted.

PMID- 9237896
TI  - The role of host factors in the population dynamics of selfish transposable
      elements.
AB  - Previous models of the evolution of selfish transposable genetic elements have
      failed to include the possibility that transposition may be limited by shortage
      of a host-encoded factor. The titration of host factors may be important in
      limiting the rate of transpositional increase in these elements. This will be
      exacerbated if multiple copies of the host factor protein must bind
      simultaneously to the target element. In the case of the Drosophila melanogaster
      P transposable element, which can exist as autonomous and as non-autonomous
      copies, there is evidence that a host-encoded protein, IRBP, is required for the
      transposition process. We have produced a specific model of the invasion of a
      host population by the P element, in which we have incorporated the requirement
      for the multiple binding of a host factor. We find that, for the P family, in
      which it is apparently transposition itself that creates selective harm to the
      host, the effect of selection in the context of host factor limitation is to
      drive up copy number. This can result in a novel high copy number-low
      transposition state. We also find that host factor limitation reinforces the
      tendency for transposable elements that create sterility to be replaced by their
      deletion derivatives.

PMID- 9237897
TI  - Dendritic nucleic acid structures.
AB  - Dendritic molecules are highly-branched arborescent structures and have found
      applications as chemical reagents, lubricants, contrast media for magnetic
      resonance, and others. Dendritic nucleic acids could be extremely useful for the
      development of nucleic acid diagnostics as signal amplification tools and
      potentially as drug (antisense) delivery vehicles. Further, due to the relatively
      large size of nucleic acid molecules, nucleic acid dendrimers could be readily
      labeled with numerous fluorescent compounds and/or protein moieties with limited
      steric hindrance and/or quenching. Herein, we present a physical-mathematical
      model of a new class of dendrimers, constructed entirely from unique nucleic acid
      monomers that are designed such that sequential hybridization adds successive
      layers of monomer in a geometric expansion of both mass and free single-stranded
      sequences, called arms, at the surface. The specially designed monomer is a
      heterodimer of two single-stranded nucleic acid oligomers possessing a central
      double-stranded waist and four single-stranded arms for binding. Assembly of a
      dendrimer is initiated from a single monomer and proceeds in layers, the first
      comprising four monomers, which provides 12 single-stranded arms. Thus, the
      second layer adds 12 monomers resulting in 36 single-stranded arms. After
      addition of the 6th layer, the dendrimer is comprised of 1457 monomers, of which
      972 reside in the 6th layer, which possesses 2916 single-stranded arms. The
      accompanying mathematical description of a dendrimer's growth is generic. A
      natural consequence and limiting condition of the growth process we describe is a
      saturated solution of nucleic acid, which is, in effect, a "nucleic acid
      membrane".

PMID- 9237899
TI  - Role of mitochondrial GrpE and phosphate in the ATPase cycle of matrix Hsp70.
AB  - The yeast mitochondrial GrpE homologue, Mge1, assists matrix Hsp70 in both
      protein translocation across the mitochondrial membranes and subsequent protein
      folding. We expressed mtHsp70 and Mge1 in Escherichia coli and analyzed their
      function in the ATP hydrolysis cycle. Mge1 stimulates ATP hydrolysis by mtHsp70
      about twofold. Addition of inorganic phosphate inhibits ATP hydrolysis by
      preventing ADP release from mtHsp70. Mge1 has no direct effect on gamma-phosphate
      release from mtHsp70, yet indirectly relieves the phosphate inhibition by
      stimulating ADP release. We conclude that Mge1 promotes the ATPase cycle of
      mtHsp70 by increasing the rate of ADP release. ATP then rapidly binds to mtHsp70
      such that the total amount of mtHsp70-bound nucleotide is not changed by Mge1.

PMID- 9237900
TI  - Effect of cytosine methylation on DNA-DNA recognition at CpG steps.
AB  - Although DNA methylation is a fundamental mechanism for repressing genetic
      activity, the influence of methyl groups on DNA conformation is found to be
      small. In this study, the role of cytosine methylation is analysed in the context
      of DNA condensation by examining its influence on DNA-DNA recognition processes.
      Previously CpG sites were found to act as sequence determinants for the close and
      specific self-fit of B-DNA helices into cross-overs. In the present study, the
      crystal structure of the B-DNA dodecamer d(ACCGCCGGCGCC) methylated at its
      central CpG sequence shows that the methyl groups do not interfere with DNA self
      fitting. In contrast, the two methyl groups form a clamp, which traps the
      incoming phosphate in the groove-backbone interaction. This geometry allows the
      formation of two new C-H...O hydrogen bonds between the methyl groups and the
      anionic oxygen atoms of the phosphate, which may further stabilize the
      interaction. This finding relates cytosine methylation to the formation of higher
      order DNA structures and could provide new insights for understanding the mode of
      action of DNA methylation in genetic inactivation.

PMID- 9237901
TI  - Assembly of functional regulatory complexes on MHC class II promoters in vivo.
AB  - Regulatory factors that bind to the X box 1 to 5 (RFX1 to RFX5) and p36 interact
      with the X box in major histocompatibility class II promoters. RFX1 and RFX5 bind
      to DNA as a homodimer (RFX1) and heterodimer with p36 (RFX5:p36, the RFX
      complex), respectively. In this study, we characterized the binding of RFX1 and
      the RFX complex to the X box in vivo, and evaluated contributions of other
      proteins that bind to flanking conserved upstream sequences (CUS: S, X, X2, and Y
      boxes) to these protein-DNA interactions. For this purpose, an intracellular DNA
      binding assay was developed. Hybrid protein effectors between RFX1 and RFX5 and
      the activation domain of VP16 from the herpes simplex virus were co-expressed
      with plasmid targets, which contained the isolated X box, X box and selected
      flanking CUS, or the entire DRA promoter. Whereas RFX1 bound better to isolated X
      boxes, the Y box selected for the binding of the RFX complex and against the
      binding of RFX1 to the X box. With proper spacing, S and X boxes stabilized the
      binding of both RFX1 and the RFX complex. The X2 box did not contribute
      significantly to the binding of either RFX1 or the RFX complex to the X box.
      Thus, complex protein-protein and protein-DNA interactions dictate the binding of
      functionally relevant proteins to conserved upstream sequences which regulate
      class II transcription.

PMID- 9237902
TI  - Activation of RpoS-dependent proP P2 transcription by the Fis protein in vitro.
AB  - The proP gene, encoding a transporter of the osmoprotecting compounds proline and
      glycine betaine, is expressed from two promoters. Transcription of the P2
      promoter occurs at a transient period in late exponential phase and is dependent
      upon Fis and the RpoS (sigma38) sigma factor. Here we characterize Fis-mediated
      activation of the P2 promoter in vitro. We find that this promoter displays
      unusually high specificity for sigma38. Fis strongly activates P2 when bound to
      site I centered at -41 within the promoter region. There is a complex
      relationship involving DNA supercoiling and potassium glutamate concentration on
      Fis activation, but most efficient transcription occurs under high salt
      conditions when the superhelical density is above -0.03. The major stimulatory
      effect of DNA supercoiling occurs between superhelical densities of 0 to -0.02
      suggesting that, while supercoiling is mechanistically important, it may not be a
      physiologically relevant controlling factor. However, the stimulation of
      transcription by high potassium glutamate concentrations may contribute to the
      osmotic inducibility of the P2 promoter. We show that Fis and E sigma38 bind
      cooperatively on supercoiled DNA to form a stable complex at P2 that involves
      promoter melting. Fis also binds to a second site within the proP regulatory
      region. While binding to this site appears to play no role in Fis activation of
      the P2 promoter, it functions as a repressor of transcription initiating from the
      P1 promoter by either sigma70 or sigma38.

PMID- 9237903
TI  - Expression of a coronavirus ribosomal frameshift signal in Escherichia coli:
      influence of tRNA anticodon modification on frameshifting.
AB  - Eukaryotic ribosomal frameshift signals generally contain two elements, a
      heptanucleotide slippery sequence (XXXYYYN) and an RNA secondary structure, often
      an RNA pseudoknot, located downstream. Frameshifting takes place at the slippery
      sequence by simultaneous slippage of two ribosome-bound tRNAs. All of the tRNAs
      that are predicted to decode frameshift sites in the ribosomal A-site (XXXYYYN)
      possess a hypermodified base in the anticodon-loop and it is conceivable that
      these modifications play a role in the frameshift process. To test this, we
      expressed slippery sequence variants of the coronavirus IBV frameshift signal in
      strains of Escherichia coli unable to modify fully either tRNA(Lys) or tRNA(Asn).
      At the slippery sequences UUUAAAC and UUUAAAU (underlined codon decoded by
      tRNA(Asn), anticodon 5' QUU 3'), frameshifting was very inefficient (2 to 3%) and
      in strains deficient in the biosynthesis of Q base, was increased (AAU) or
      decreased (AAC) only two-fold. In E. coli, therefore, hypomodification of
      tRNA(Asn) had little effect on frameshifting. The situation with the efficient
      slippery sequences UUUAAAA (15%) and UUUAAAG (40%) (underlined codon decoded by
      tRNA(Lys), anticodon 5' mnm5s2UUU 3') was more complex, since the wobble base of
      tRNA(Lys) is modified at two positions. Of four available mutants, only trmE
      (s2UUU) had a marked influence on frameshifting, increasing the efficiency of the
      process at the slippery sequence UUUAAAA. No effect on frameshifting was seen in
      trmC1 (cmnm5s2UUU) or trmC2 (nm5s2UUU) strains and only a very small reduction
      (at UUUAAAG) was observed in an asuE (mnm5UUU) strain. The slipperiness of
      tRNA(Lys), therefore, cannot be ascribed to a single modification site on the
      base. However, the data support a role for the amino group of the mnm5
      substitution in shaping the anticodon structure. Whether these conclusions can be
      extended to eukaryotic translation systems is uncertain. Although E. coli
      ribosomes changed frame at the IBV signal (UUUAAAG) with an efficiency similar to
      that measured in reticulocyte lysates (40%), there were important qualitative
      differences. Frameshifting of prokaryotic ribosomes was pseudoknot-independent
      (although secondary structure dependent) and appeared to require slippage of only
      a single tRNA.

PMID- 9237905
TI  - DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a
      mechanism-based probe.
AB  - The mechanisms that establish and maintain methylation patterns in the mammalian
      genome are very poorly understood, even though perturbations of methylation
      patterns lead to a loss of genomic imprinting, ectopic X chromosome inactivation,
      and death of mammalian embryos. A family of sequence-specific DNA
      methyltransferases has been proposed to be responsible for the wave of de novo
      methylation that occurs in the early embryo, although no such enzyme has been
      identified. A universal mechanism-based probe for DNA (cytosine-5)
      methyltransferases was used to screen tissues and cell types known to be active
      in de novo methylation for new species of DNA methyltransferase. All identifiable
      de novo methyltransferase activity was found to reside in Dnmt1. As this enzyme
      is the predominant de novo methyltransferase at all developmental stages
      inspected, it does not fit the definition of maintenance methyltransferase or
      hemimethylase. Recent genetic data indicate that de novo methylation of
      retroviral DNA in embryonic stem cells is likely to involve one or more
      additional DNA methyltransferases. Such enzymes were not detected and are either
      present in very small amounts or are very different from Dnmt1. A new method was
      developed and used to determine the sequence specificity of intact Dnmt1 in whole
      cell lysates. Specificity was found to be confined to the sequence 5'-CpG-3';
      there was little dependence on sequence context or density of CpG dinucleotides.
      These data suggest that any sequence-specific de novo methylation mediated by
      Dnmt1 is either under the control of regulatory factors that interact with Dnmt1,
      or is cued by alternative secondary structures in DNA.

PMID- 9237904
TI  - Characterization of peptides that bind the tumor-associated Thomsen-Friedenreich
      antigen selected from bacteriophage display libraries.
AB  - Peptides with high affinities and specificities for numerous proteins and nucleic
      acids have been previously identified from random peptide bacteriophage display
      libraries. Here, random peptide bacteriophage display libraries were used to
      identify sequences that bound the cancer-associated Thomsen-Friedenreich
      glycoantigen (T antigen). The T antigen, present on most malignant cells,
      contains an immunodominant Gal beta1 --> 3GalNAc alpha disaccharide unmasked on
      the surfaces of most carcinomas. This antigen has been postulated to be involved
      in tumor cell aggregation and metastasis. Two 15 amino acid random peptide
      bacteriophage display libraries were affinity selected with glycoproteins
      displaying T antigen on their surfaces. Sequence analysis revealed that many of
      the peptides shared homology with sugar recognition sites in several carbohydrate
      binding proteins. A comparison of affinity selected sequences from both libraries
      yielded a common motif (W-Y-A-W/F-S-P) rich in aromatic amino acids. Four
      peptides, corresponding to the affinity selected sequences, were chemically
      synthesized and characterized for their carbohydrate recognition properties. The
      synthetic peptides exhibited high specificities and affinities to T antigen
      displayed on asialofetuin or conjugated to bovine serum albumin (Kd = 5 nM for
      MAP-P30 binding to asialofetuin) as well as free T-antigen disaccharide in
      solution (Kd = 10 microM for MAP-P30, 20 microM for P10). Two peptides, P30 and
      P10, demonstrated high affinities and specificities for both asialofetuin and T
      antigen in solution. Iodination of a lone tyrosine residue in each sequence
      dramatically reduced their abilities to bind T antigen, suggesting that the
      tyrosine residue plays an important role in carbohydrate recognition. That these
      peptides are of functional significance is evidenced by the ability of both P30
      and P10 to inhibit asialofetuin-mediated melanoma cell aggregation in vitro and
      to compete with peanut lectin for binding to T antigen displayed on the surface
      of MDA-MB-435 breast carcinoma cells in situ.

PMID- 9237906
TI  - Communications between distant sites on supercoiled DNA from non-exponential
      kinetics for DNA synapsis by resolvase.
AB  - To determine how distant sites on supercoiled DNA communicate with each other,
      the mechanism of site-specific recombination by resolvase was analysed by using a
      rapid-reaction quench-flow device to study the kinetics of individual steps in
      the reaction pathway. Three sets of measurements revealed the rates for: (1) the
      initial binding of the protein to its target sites on the DNA; (2) the synapsis
      of the two DNA-protein complexes; (3) the overall process of recombination. The
      binding of the protein to the DNA was complete within 50 milliseconds while
      recombination required 500 seconds. Surprisingly, synapsis spanned this entire
      time range: some DNA molecules gave synaptic complexes within ten milliseconds
      after the initial binding, while others took over 100 seconds. The departure from
      exponential behaviour may be due to each molecule of DNA having to undergo
      different conformational fluctuations in order to juxtapose the recombinational
      sites. From polymer physics theory, the rate of synapsis ought to vary with
      either the size of the DNA molecule or the length of DNA between the
      recombinational sites, depending on the nature of the fluctuations, but plasmids
      of different sizes and with different spacings between the sites all gave the
      same rates for synapsis. This observation cannot be reconciled with current
      models for encounters of distant sites on supercoiled DNA. However, the
      superhelical axis in the DNA molecules used here will be branched at one or more
      positions and the encounters may arise from the motion of a single branch
      relative to the remainder of the chain. Alternatively, the non-exponential
      kinetics for synapsis may be due to multiple re-arrangements of non-productive
      complexes following DNA juxtaposition.

PMID- 9237907
TI  - Random walk models for DNA synapsis by resolvase.
AB  - During site-specific recombination by resolvase, the protein binds to two sites
      on a supercoiled DNA molecule and the loaded sites then interact with each other
      to form a synaptic complex. The kinetics of synapsis show non-exponential
      behaviour extending over five log units of time and are independent of the length
      of the DNA molecule and the length of DNA between the sites. In this study,
      numerical models were developed in order to account for how fluctuations in the
      structure of supercoiled DNA might lead to the juxtaposition of distant sites in
      a manner consistent with the experimental data on synapsis by resolvase. Models
      where the juxtaposition arises from fluctuations around branch points in the
      superhelix failed to match the data: they yielded non-exponential kinetics but
      only over two log units of time and they predicted longer synapsis times for both
      larger DNA molecules and larger inter-site spacings. In another model, one
      fraction of the juxtaposition events gives rise directly to the productive
      complex while the remaining fraction initially yields a non-productive complex:
      the latter molecules undergo no further fluctuations until the abortive synapse
      dissociates at the end of a delay period. This model again failed to match the
      experimental data. However, the inclusion of three sorts of non-productive
      complexes, each with a different delay constant, led to progress curves that
      concurred with the data. Schemes were also developed to account for the
      juxtaposition of three sites at a branch point in supercoiled DNA.

PMID- 9237908
TI  - Stability and structure of DNA oligonucleotides containing non-specific base
      analogues.
AB  - The nature of DNA containing the deoxyribosyl derivative of 5-nitroindole has
      been investigated. 5-Nitroindole has been shown to give good stability when
      present in duplexes opposite natural bases, with only slightly reduced melting
      temperatures. However, enhanced stability occurs when it is incorporated as an
      additional bulged base in duplexes. It also markedly enhances the stability of
      duplexes when it is present as a pendant base at either the 5' or 3'-ends of the
      two strands. The stabilisation is presumed to be due to enhanced stacking
      interactions for the nitroindole base. Oligomers containing a number of
      consecutive 5-nitroindole residues form stable, stacked secondary structures. An
      oligomer containing 21 such substitutions is presumed to exist as a hairpin
      structure. This was further investigated by circular dichroism melting
      experiments, which demonstrated that the single-stranded oligomer contains
      significant secondary structure in the region of the 5-nitroindole tract, which
      appears to contain a double-stranded stem. X-ray analysis of 5-nitroindole
      deoxyriboside provides some indication of how the mode of stacking observed in
      crystals of the nucleoside may also be responsible for stabilising secondary
      structures of oligonucleotides.

PMID- 9237909
TI  - Theoretical studies of an exceptionally stable RNA tetraloop: observation of
      convergence from an incorrect NMR structure to the correct one using unrestrained
      molecular dynamics.
AB  - We report on the results of five independent and unrestrained molecular dynamics
      simulations of an RNA tetraloop, r(GGACUUCGGUCC), and its related structures with
      the loop UUCG sugars changed to deoxyribose. Two separate NMR structures have
      been reported for the loop portion of this molecule, with the second refinement
      resulting in a slightly different and more accurate conformation for the loop.
      The root-mean-square deviation (RMSd) between the two NMR structures, for the
      loop portions only, is 2.5 A. Our simulations, starting from the two NMR
      structures, demonstrate that this tetraloop is a very stable and rigid structure
      with both nanosecond length simulations staying very close to the initial
      structures. Additionally, both simulations preserved most, if not all, of the NMR
      derived interactions and violated very few of the nuclear Overhauser effect (NOE)
      derived distances used in the structure refinements. However, when the two NMR
      structures were simulated with deoxyriboses in the loops instead of the native
      riboses, the flexibility of the systems increased and we observed a conversion
      from the incorrect to the correct loop conformation in the simulation which
      started in the incorrect loop conformation. When the riboses were subsequently re
      introduced back into the structure which underwent the conversion, the agreement
      between this simulation and the one starting from the correct NMR structure was a
      remarkably low 0.5 A, demonstrating an almost complete convergence from the
      incorrect to the correct structure using unrestrained molecular dynamics.

PMID- 9237910
TI  - Effects of Mg2+, K+, and H+ on an equilibrium between alternative conformations
      of an RNA pseudoknot.
AB  - A complex pseudoknot structure surrounds the first ribosome initiation site in
      the Escherichia coli alpha mRNA and mediates its regulation by ribosomal protein
      S4. A 112 nt RNA fragment containing this pseudoknot exists in two conformations
      that are resolvable by gel electrophoresis below room temperature. Between 30
      degrees C and 45 degrees C the conformers reach thermodynamic equilibrium on a
      time scale ranging from one hour to one minute, and the interconversion between
      conformers is linked to H+, K+ and Mg2+ concentrations. Mg2+ favors formation of
      the "fast" electrophoretic form: a single Mg2+ is bound in the rate-limiting
      step, followed by cooperative binding of approximately 1.7 additional ions.
      Binding of the latter ions provides most of the favorable free energy for the
      reaction. However, the "slow" form binds about the same number of Mg ions, albeit
      more weakly, so that saturating Mg2+ concentrations drive the equilibrium to only
      approximatley 70% fast form. A single H+ is taken up in the switch to the "slow"
      conformer, which has apparent pK approximately 5.9; low pH also stabilizes part
      of the pseudoknot structure melting at approximately 62 degrees C. Mg2+ and H+
      appear to direct alpha mRNA folding by relatively small (10 to 100-fold)
      differences in their affinities for alternative conformers. K+ has very little
      effect on the conformational equilibrium, but at high concentrations accelerates
      interconversion between the conformers. The alpha mRNA conformational switch is
      similar in its slow kinetics, large activation energy, and Mg2+ dependence of the
      equilibrium constant to slow steps in the folding of tRNA, group I introns, and
      RNase P RNA tertiary structures, though it differs from these in the association
      of a single Mg2+ with the rate-limiting step.

PMID- 9237911
TI  - Base-pairings within the RNA pseudoknot associated with the simian retrovirus-1
      gag-pro frameshift site.
AB  - Frameshift and readthrough sites within retroviral messenger RNAs are often
      followed by nucleotide sequences that have the potential to form pseudoknot
      structures. In the work presented here, NMR methods were used to characterize the
      base-pairings and structural features of the RNA pseudoknot downstream of the gag
      pro frameshift site of simian retrovirus type-1 (SRV-1) and a functional mutant
      of the SRV-1 pseudoknot. Evidence is presented that these pseudoknots contain two
      A-form helical stems of six base-pairs each, connected by two loops, in a classic
      H-type pseudoknot topology. A particularly interesting feature is that the
      shorter of the two connecting loops, loop 1, consists of only a single adenosine
      nucleotide that spans the major groove of stem 2. In this respect, the frameshift
      associated pseudoknots are structurally similar to the pseudoknot within the gene
      32 mRNA of bacteriophage T2, previously characterized by NMR methods. Despite
      having similar nucleotide sequences, the solvent exchange rates of the imino
      protons at the junction of the helical stems in the wild-type and mutant
      frameshifting pseudoknots differ from each other and from the bacteriophage T2
      pseudoknot. The implications of this finding are discussed.

PMID- 9237912
TI  - Protein fold recognition by prediction-based threading.
AB  - In fold recognition by threading one takes the amino acid sequence of a protein
      and evaluates how well it fits into one of the known three-dimensional (3D)
      protein structures. The quality of sequence-structure fit is typically evaluated
      using inter-residue potentials of mean force or other statistical parameters.
      Here, we present an alternative approach to evaluating sequence-structure
      fitness. Starting from the amino acid sequence we first predict secondary
      structure and solvent accessibility for each residue. We then thread the
      resulting one-dimensional (1D) profile of predicted structure assignments into
      each of the known 3D structures. The optimal threading for each sequence
      structure pair is obtained using dynamic programming. The overall best sequence
      structure pair constitutes the predicted 3D structure for the input sequence. The
      method is fine-tuned by adding information from direct sequence-sequence
      comparison and applying a series of empirical filters. Although the method relies
      on reduction of 3D information into 1D structure profiles, its accuracy is,
      surprisingly, not clearly inferior to methods based on evaluation of residue
      interactions in 3D. We therefore hypothesise that existing 1D-3D threading
      methods essentially do not capture more than the fitness of an amino acid
      sequence for a particular 1D succession of secondary structure segments and
      residue solvent accessibility. The prediction-based threading method on average
      finds any structurally homologous region at first rank in 29% of the cases
      (including sequence information). For the 22% first hits detected at highest
      scores, the expected accuracy rose to 75%. However, the task of detecting entire
      folds rather than homologous fragments was managed much better; 45 to 75% of the
      first hits correctly recognised the fold.

PMID- 9237913
TI  - fd coat protein structure in membrane environments: structural dynamics of the
      loop between the hydrophobic trans-membrane helix and the amphipathic in-plane
      helix.
AB  - By performing multidimensional solution NMR experiments on micelle samples it was
      possible to determine the structure of the membrane-bound form of fd coat protein
      based on short-range distance and dihedral angle constraints using distance
      geometry and simulated annealing calculations. Its dynamics were described by 15N
      relaxation measurements (T1, T2, heteronuclear nuclear Overhauser enhancement
      (NOE)) fitted with the Lipari-Szabo model-free formalism adapted for the
      transmembrane and in-plane helices of a membrane protein. The overall correlation
      time of the protein in micelles was found to be approximately 9 ns, and the local
      motion of each backbone N-H vector was described by an order parameter and an
      effective correlation time. The 50 residue protein has an amphipathic alpha-helix
      (residues 7 to 16) and a hydrophobic alpha-helix (residues 27 to 44), which were
      found to be approximately perpendicular on the basis of NOEs in the residues that
      connect the two helices. The residues connecting the helices are of particular
      interest in membrane proteins, and in this case the loop consists of two turns.
      The relaxation data show the presence of an extra motion in the amphipathic alpha
      helix on the nanosecond timescale and additional flexibility of several residues
      in the loop connecting the two helices.

PMID- 9237914
TI  - Three-dimensional structure of the DNA-binding domain of the fructose repressor
      from Escherichia coli by 1H and 15N NMR.
AB  - FruR is an Escherichia coli transcriptional regulator that belongs to the LacI
      DNA-binding protein family. By using 1H and 15N NMR spectroscopy, we have
      determined the three-dimensional solution structure of the FruR N-terminal DNA
      binding domain consisting of 57 amino acid residues. A total of 809 NMR-derived
      distances and 54 dihedral angle constraints have been used for molecular
      modelling with the X-PLOR program. The resulting set of calculated structures
      presents an average root-mean-square deviation of 0.37 A at the main-chain level
      for the first 47 residues. This highly defined N-terminal part of the structure
      reveals a similar topology for the three alpha-helices when compared to the 3D
      structures of LacI and PurR counterparts. The most striking difference lies in
      the connection between helix II and helix III, in which three additional residues
      are present in FruR. This connecting segment is well structured and contains a
      type III turn. Apart from hydrophobic interactions of non-polar residues with the
      core of the domain, this connecting segment is stabilised by several hydrogen
      bonds and by the aromatic ring stacking between Tyr19 of helix II and Tyr28 of
      the turn. The region containing the putative "hinge helix" (helix IV), that has
      been described in PurR-DNA complex to make specific base contacts in the minor
      groove of DNA, is unfolded. Examination of hydrogen bonds highlights the
      importance of homologous residues that seem to be conserved for their ability to
      fulfill helix N and C-capping roles in the LacI repressor family.

PMID- 9237915
TI  - Crystal structure of r(GUGUGUA)dC with tandem G x U/U x G wobble pairs with
      strand slippage.
AB  - To better understand the frequent occurrence of adjacent wobble pairs in
      ribosomal RNAs we have determined the crystal structure of the RNA duplex,
      r(GUGUGUA)dC with the 3'-terminal deoxy C residue. Two different crystal forms of
      the duplex were obtained and both belong to the rhombohedral space group, R3.
      Crystal form I has hexagonal unit cell dimensions, a = b = 40.82 A and c = 66.09
      A and diffracts to 1.58 A resolution, while crystal form II has a = b = 47.11 A
      and c = 59.86 A, diffracting only to 2.50 A resolution. Both structures were
      solved by the molecular replacement method using different starting models. In
      spite of the large differences in the cell dimensions the overall structures in
      both crystals are similar. Instead of the expected blunt-end duplex with four
      consecutive G x U pairs, the slippage of the strands resulted in two different
      tandem G x U/U x G wobble pairs involving two of the central and two of the 5'
      overhang bases, still yielding a total of four wobble pairs. These tandem wobble
      pairs are flanked by two Watson-Crick pairs. The A-type duplexes stack in the
      familiar head-to-tail fashion forming a pseudocontinuous helix. The wobble pairs
      of the present motif II (G x U/U x G) structure stack with a low twist angle of
      25.3 degrees in contrast to that of motif I (U x G/G x U), 38.1 degrees. The four
      wobble pairs are characteristically heavily hydrated in both the grooves
      accounting for their stability.

PMID- 9237917
TI  - Stochastic Token Theory
AB  - This paper presents a theory encompassing a collection of stochastic models
      developed earlier and concerning the evolution of subjective preferences under
      the influence of a stream of elementary events. The theory relies on two basic
      concepts. (1) The states: Each individual in the population of reference is
      regarded as evolving in real time through a sequence of internal states. These
      states can be probed by interviewing the subjects at some arbitrarily chosen
      times t1,  em leader, tn. Each of these interviews yields a response which is a
      reflection of the current state. (2) The tokens: The individual is subjected to a
      stochastic stream of unobservable or unrecorded "particles" of information,
      called tokens. Each token has the potential of modifying the current state, and
      is accordingly formalized by a transformation on the set of states. The core of
      the theory and the major concern of this paper is the particular semigroup
      generated by all such transformations. Combinatorial and stochastic axioms are
      formulated which lead to testable conditions. The theorems of this paper
      generalize earlier results by the author and others.

PMID- 9237916
TI  - Calculation of the dielectric properties of a protein and its solvent: theory and
      a case study.
AB  - This paper presents a rigorous derivation of a theory for the calculation of the
      frequency-dependent dielectric properties of each component of the system
      protein/water/ions with the aim of enabling comparison to experimentally
      determined dielectric properties. We apply this theory to a very long (13.1 ns)
      molecular dynamics simulation of an HIV1 zinc finger peptide, its co-ordinated
      zinc ion, and two chloride ions in a box of SPC/E water molecules. We find the
      dielectric relaxation of the water molecules restricted compared to pure water,
      giving rise to a static dielectric constant for the water-component of only 47.
      The peptide is found to have a complicated dielectric relaxation behaviour, with
      a static dielectric constant of 15. We also calculate the frequency-dependent
      conductivity of the ions in this system. We analyze all contributions to the
      calculation of these dielectric properties and find that the coupling between the
      dielectric relaxation of the peptide and that of the water-component is
      particularly important for correctly describing the dielectric constant of the
      peptide.

PMID- 9237918
TI  - The Structure of Perceptual Categories
AB  - When presented with a small set of sample objects, human observers have the
      striking capacity to induce a more general class. Generalization can even proceed
      from a single object ("one-shot categorization"). The inference is apparently
      guided by the principle that a good categorical hypothesis is one in which the
      observed object would be a typcal, "non-accidental," or generic example; this
      idea is formalized here as the Genericity Constraint. In the theory proposed
      here, each categorical hypothesis is a "generative model," a sequence of
      transformations by which the object is interpreted as having been created;
      objects are considered to be in the same category if they were created by the
      same set of operations. The set of all available category models can be
      explicitly enumerated in a lattice, an explicit structure that partially orders
      the models by their degree of regularity or genericity-more abstract models are
      higher in the lattice, and more regular or constrained models are lower. The
      Genericity Constraint dictates that among all the models on the lattice that
      apply, the observer should choose the one in which the observed object is
      generic, which is simply the lowest in the partial order. A series of experiments
      are reported in which subjects are asked to generalize from simple figures. The
      results corroborate the role of the lattice and the Genericity Constraint in
      subjects' interpretations

PMID- 9237919
TI  - An Approval-Voting Polytope for Linear Orders
AB  - A probabilistic model of approval voting on n alternatives generates a collection
      of probability distributions on the family of all subsets of the set of
      alternatives. Focusing on the size-independent model proposed by Falmagne and
      Regenwetter, we recast the problem of characterizing these distributions as the
      search for a minimal system of linear equations and inequalities for a specific
      convex polytope. This approval-voting polytope, with n! vertices in a space of
      dimension 2(n), is proved to be of dimension 2(n)-n-1. Several families of facet
      defining linear inequalities are exhibited, each of which has a probabilistic
      interpretation. Some proofs rely on special sequences of rankings of the
      alternatives. Although the equations and facet-defining inequalities found so far
      yield a complete minimal description when n<=4 (as indicated by the PORTA
      software), the problem remains open for larger values of n.

PMID- 9237920
TI  - Triadic Distance Models: Axiomatization and Least Squares Representation
AB  - Distance models for three-way proximity data, which consist of numerical values
      assigned to triples of objects that indicate their joint (lack of) homogeneity or
      resemblance, require a generalization of the usual distance concept defined on
      pairs of objects. An axiomatic framework is given for characterizing triadic
      dissimilarity, triadic similarity, and triadic distance, where the term triadic
      implies that each element of the triple is treated on an equal footing. Two kinds
      of distance models are studied in detail: the Minkowski-p or Mp model, which is
      based upon dyadic components and includes the perimeter model as an important
      special case, and several models based on presence-absence variables. They are
      shown to satisfy the tetrahedral inequality, a condition that is characteristic
      for the present axiomatization. Two monotonically convergent algorithms are
      described that find weighted least squares representations of three-way proximity
      data under the Euclidean M1 model and the Euclidean M2 model. To enable a
      scalefree evaluation of the quality of the fit, an additive decomposition of the
      sum of squares of the dissimilarities is derived. As illustrated in one of the
      examples, distance analysis of three-way, three-mode tables is possible by a
      suitable manipulation of the least squares weights.

PMID- 9237927
TI  - Immune response decisions at the single cell level.
AB  - Helper T cells regulate the progressive differentiation of antigen-specific B
      cells in complex and dynamic microenvironments in vivo. In this review, antigen
      driven B-cell differentiation will be discussed in three phases: pre-germinal
      center, germinal center and post-germinal center. Each phase of the response
      appears to have unique cellular starting points, specialized regional
      microenvironments and its own set of controls and cellular outcomes. Decisions
      made by individual lymphocytes at each of these phases determines the shape of
      protective immunity in vivo.

PMID- 9237928
TI  - Memory B-cell clones and the diversity of their members.
AB  - Memory B-cell clones develop from virgin B cells that take up processed antigen,
      make cognate interaction with primed T cells and then grow in germinal centres.
      Within the germinal centre the proliferating B cells undergo Ig variable-region
      mutation and are subsequently selected on their ability to bind antigen held on
      follicular dendritic cells and then to make cognate interaction with germinal
      centre T cells. The selected cells emerge as memory B cells or plasmablasts.
      Although many of the memory B cells and most of the plasma cells emerging from
      follicles have undergone Ig class switch recombination a substantial minority of
      the memory B cells have not switched. These non-switched memory cells can be
      induced to switch on re-exposure to antigen. Affinity maturation following a
      single immunization ceases as germinal centres wane some 3-4 weeks after
      immunization - memory cells and antibody production, on the other hand, persist
      for months and even years.

PMID- 9237929
TI  - Regulation of B-cell commitment to plasma cells or to memory B cells.
AB  - During humoral immune responses, B-lymphocyte activation is followed by
      differentiation along either the plasma cell pathway or the memory B-cell
      pathway. Recent studies suggest that CD40-CD40 ligand, OX-OX40 ligand, a group of
      cytokines and intracellular transcriptional factors may all contribute to B
      lymphocyte differentiation control.

PMID- 9237930
TI  - The cellular origins of memory B cells.
AB  - Recent evidence indicates that memory B cells may originate from a precursor cell
      subset that is distinct from AFC precursors. Most convincing is the finding that
      fractionation of naive peripheral B-cell populations on the basis of surface heat
      stable antigen (HSA) expression yields two populations; one greatly enriched for
      progenitors of memory B cells (HSAlo), and the other enriched for AFC precursors
      (HSAint-hi). Antigenic stimulation of HSAlo B cells in vitro leads to the
      generation of memory B-cell clones in the absence of any detectable antibody
      formation whereas stimulation of HSAint-hi cells yield AFC responses but not
      memory B cells. Furthermore, the progeny of HSAlo cells are unique in their
      ability to accumulate somatic mutations and originate germinal centers (GC). The
      pre-existence of two distinct precursor cell populations may help resolve the
      disparate biological characteristics of AFC precursors which appear to be
      terminally differentiated versus memory progenitors which retain stem cell
      characteristics in their capacity to self renew, undergo multiple divisions, and
      generate progeny that express enzymes characteristic of stem cells or pro-pre B
      cells and acquire tolerance susceptibility.

PMID- 9237931
TI  - Observations on memory B-cell development.
AB  - We dissect in this article the roles of CD40 and its ligand in memory B-cell
      formation. Our data indicate that CD40 ligation does not directly lead to GC
      formation but it plays an indirect role related to maturation of helper T cells;
      signalling is bidirectional, to B cells, via CD40, upregulating cytokine receptor
      expression and to T cells, via CD40L, causing secretion of cytokines necessary
      for GC initiation. Later in the GC, CD40 selects mutated B cells for entry into
      the memory pool. This second T-cell-mediated CD40 ligation has consequences
      distinct from the first (rescue versus proliferation) that arise from rewiring of
      CD40 signal transduction pathways.

PMID- 9237932
TI  - Distinctive characteristics of germinal center B cells.
AB  - A cardinal property of the immune system is its ability to respond to an antigen
      that was encountered years before with an accelerated and enhanced secondary
      response. The property of anamnestic reactions depends upon the formation of long
      lived compartments of specialized T and B lymphocytes called memory cells. While
      the origin of the memory T-cell compartment is not known, germinal centers are
      the specialized sites for memory B-cell generation and the immunoglobulin V
      region hypermutation necessary for the affinity maturation of serum antibody.
      Interestingly, the peripheral differentiation pathway that leads to this most
      mature B-cell state begins with the recapitulation of many characters of immature
      B lymphocytes in bone marrow. This review describes the distinctive cellular
      basis of germinal center reaction and the characteristics of B cells in germinal
      centers that later enter the memory pool.

PMID- 9237933
TI  - B-cell activation and development within chronically inflamed synovium in
      rheumatoid and reactive arthritis.
AB  - In autoimmune diseases, B cells often accumulate in the affected tissue. In
      patients with rheumatoid arthritis or reactive arthritis, germinal center-like
      structures may develop in the inflamed synovial tissue. B cells from these
      structures were isolated and their V-gene repertoire determined. The majority of
      synovial B cells are long-term memory cells and thus are part of the chronic
      inflammatory reaction. In the synovium a micro-environment is built up which
      allows the activation of naive and memory B cells and the diversification of
      their V-gene repertoire. The analysis of plasma cells suggests that these cells
      are long lived and hence accumulate in the synovial tissue under chronic
      activation.

PMID- 9237934
TI  - Mattie Rae Spivey Fox (1923-1988).

PMID- 9237935
TI  - Dietary supplementation with gamma-linolenic acid alters fatty acid content and
      eicosanoid production in healthy humans.
AB  - To understand the in vivo metabolism of dietary gamma-linolenic acid (GLA), we
      supplemented the diets of 29 volunteers with GLA in doses of 1.5-6.0 g/d. Twenty
      four subjects ate controlled eucaloric diets consisting of 25% fat; the remaining
      subjects maintained their typical Western diets. GLA and dihomo-gamma-linolenic
      acid (DGLA) increased in serum lipids of subjects supplemented with 3.0 and 6.0
      g/d; serum arachidonic acid increased in all subjects. GLA supplementation with
      3.0 and 6.0 g/d also resulted in an enrichment of DGLA in neutrophil
      phospholipids but no change in GLA or AA levels. Before supplementation, DGLA was
      associated primarily with phosphatidylethanolamine (PE) of neutrophil
      glycerolipids, and DGLA increased significantly in PE and neutral lipids after
      GLA supplementation. Extending the supplementation to 12 wk did not consistently
      change the magnitude of increase in either serum or neutrophil lipids in subjects
      receiving 3.0 g/d. After GLA supplementation, A23187-stimulated neutrophils
      released significantly more DGLA, but AA release did not change. Neutrophils
      obtained from subjects after 3 wk of supplementation with 3.0 g/d GLA synthesized
      less leukotriene B4 (P < 0.05) and platelet-activating factor. Together, these
      data reveal that DGLA, the elongase product of GLA, but not AA accumulates in
      neutrophil glycerolipids after GLA supplementation. The increase in DGLA relative
      to AA within inflammatory cells such as the neutrophil may attenuate the
      biosynthesis of AA metabolites and may represent a mechanism by which dietary GLA
      exerts an anti-inflammatory effect.

PMID- 9237936
TI  - Cellular glutathione peroxidase knockout mice express normal levels of selenium
      dependent plasma and phospholipid hydroperoxide glutathione peroxidases in
      various tissues.
AB  - Selenium-dependent cellular glutathione peroxidase (GPX1) knockout [GPX1(-)] mice
      were derived from 129/SVJ x C57BL/6 hybrid mice by microinjecting C57BL/6
      blastocysts with recombinant embryonic stem cells carrying a target mutation in
      the GPX1 gene. Experiment 1 was conducted to determine the effects of the GPX1
      knockout on the susceptibility of mice to dietary vitamin E and Se deficiency and
      on the expression of the Se-dependent plasma glutathione peroxidase (GPX3) and
      phospholipid hydroperoxide glutathione peroxidase (GPX4), and the Se-independent
      glutathione S-transferase (GST). Eleven GPX1(-) and 11 control mice (5 wk old,
      six males and five females) were fed a Se-deficient, Torula yeast basal diet
      (0.02 mg Se/kg, no supplemental vitamin E) or the basal diet supplemented with
      0.5 mg Se/kg (as Na2SeO3) for 13 wk. Experiment 2 was conducted to determine the
      effect of the GPX1 knockout on the total Se concentration in the liver of Se
      adequate mice. Six GPX1(-) and four control mice (5 wk old, half males and
      females) were fed the basal diet supplemented with 0.2 mg Se/kg and 15 mg of all
      rac-alpha-tocopheryl acetate/kg for 5 wk. There was no difference in body weight
      gain or apparent susceptibility to dietary vitamin E and Se deficiency between
      the GPX1(-) and control mice. Knockout of GPX1 resulted in almost complete
      abolishment of GPX1 activity in various tissues, but had no effect on the GPX3 or
      GPX4 mRNA level and activity or the GST activity in several tissues at either
      level of dietary Se. The liver total Se concentration in the Se-adequate GPX1(-)
      mice was only 42% of that in the controls (P < 0. 0001). These results indicate
      that GPX1 is expressed independently of GPX3 or GPX4 and represents approximately
      60% of the total hepatic Se in Se-adequate mice.

PMID- 9237937
TI  - Long-term oral supplementation with iron is not harmful for young children in a
      poor community of Bangladesh.
AB  - The effect of long-term oral iron supplementation on morbidity due to diarrhea,
      dysentery and respiratory infections in 349 children, aged 2-48 mo, living in a
      poor community of Bangladesh, was evaluated in this double-blind study. The
      treatment group received 125 mg of ferrous gluconate (15 mg elemental iron) plus
      multivitamins and the controls received only multivitamins, daily for 15 mo.
      House-to-house visits were made on alternate days by trained community health
      workers for recording symptoms and duration of illnesses and for monitoring
      medicine intake. Seventy-six percent of the children continued the syrup for over
      1 y. No untoward effects were noticed in either treatment group. The attack rates
      for diarrhea, dysentery and acute respiratory tract infections (ARI) were 3, 3
      and 5 episodes per child per year, respectively. Each episode of diarrhea lasted
      a mean of 3 d, and those of dysentery and ARI, 5 d. The two treatment groups did
      not differ in the number of episodes, mean duration of each episode, or total
      days of illnesses due to diarrhea, dysentery and ARI. However, a 49% greater
      number of episodes of dysentery was observed with iron supplementation in a
      subset of the study children who were less than 12 mo old (P = 0.03). The results
      of this study suggest that long-term oral iron supplementation is not harmful for
      older children in a poor community. Further studies are needed to demonstrate the
      safety and efficacy of iron administration in young infants.

PMID- 9237938
TI  - Adjustment of iron intake for dietary enhancers and inhibitors in population
      studies: bioavailable iron in rural and urban residing Russian women and
      children.
AB  - Although determining iron intakes is essential in assessing adequacy of iron in
      the diet, estimating iron availability may be more useful for evaluating whether
      iron requirements are met. Our objectives were to describe the dietary
      information, analytical steps, and computer algorithms needed for iron
      bioavailability adjustments and to demonstrate the effects of various dietary
      factors on calculated iron absorption. Our study was based on 9890 women and
      children participating in the Russian Longitudinal Monitoring Survey. Between
      August 1992 and February 1993, two 24-h recalls were collected from each
      participant, and total, heme and nonheme iron intakes were calculated. Nonheme
      iron availability was adjusted for meat, fish and poultry and vitamin C consumed
      in the same meal and then further adjusted for tea and phytates. We found mean
      total iron intakes to be comparable to those of women of reproductive age in the
      United States and lower than those of United States children. When these intakes
      were adjusted for enhancers and inhibitors of absorption, the iron
      bioavailability in these vulnerable Russian groups was extremely low. Mean
      bioavailable iron as well as the 25th-75th percentile ranges of intake were below
      the bottom of the range of requirements, indicating that iron adequacy in this
      population may be considerably less than expected based on total iron intakes
      alone. Furthermore, rural and urban food availability had a significant effect on
      iron bioavailability. Future research on dietary iron adequacy should be based on
      estimates of available iron by collecting meal-level dietary data and using
      detailed information on mixed dishes and phytates.

PMID- 9237939
TI  - Transferrin kinetics are altered in children with severe protein-energy
      malnutrition.
AB  - This study was undertaken to determine the following: 1) the kinetic changes
      responsible for the depletion and repletion of plasma transferrin (Tr)
      concentration in children with protein-energy malnutrition (PEM); 2) the role of
      infection in mediating these changes; and 3) whether plasma Tr concentration is
      related to body protein status. We measured plasma Tr concentration, and
      fractional (FSR) and absolute (ASR) Tr synthesis rates with the use of a constant
      intragastric infusion of 2H3-leucine in 14 children with PEM, at 2 d
      postadmission (study 1), 8 d postadmission when infections were under control
      (study 2), and at recovery (study 3). In studies 1 and 2, the children
      synthesized less Tr and had lower Tr concentrations compared with values at
      recovery. When infections were controlled, plasma Tr concentration rose, but Tr
      synthesis was unchanged. There were only fair correlations (P < 0. 05) between
      plasma Tr concentrations and indices of wasting. Concerning malnourished
      children, we reached the following conclusions: 1) changes in the Tr pool size
      are achieved mainly through changes in synthesis rate; 2) infections play a minor
      role in reducing the Tr pool through either changes in the rate of catabolism or
      loss from the intravascular space; and 3) Tr concentration is not a very good
      indicator of protein nutritional status.

PMID- 9237940
TI  - Accumulation and clearance of capsanthin in blood plasma after the ingestion of
      paprika juice in men.
AB  - The pharmacokinetics of dietary capsanthin was measured in four male volunteers
      to assess the bioavailability of oxygenated carotenoids (xanthophylls).
      Capsanthin was used because this carotenoid was not detected in the men's plasma
      before ingestion of paprika juice. Supplementing capsanthin-rich paprika juice
      for 1 wk (equivalent to three doses of 5.4 micromol capsanthin/d; 16.2
      micromol/d), the level of capsanthin reached a plateau (0.10-0.12 micromol/L)
      between d 2 and 7 and was not detectable by d 16. Capsanthin was distributed in
      the plasma lipoproteins (VLDL, 13 +/- 3%; LDL , 44 +/- 3%; HDL, 43 +/- 3%) at the
      end of the experiment. In a separate experiment involving the single ingestion of
      paprika juice (equivalent to 34.2 micromol capsanthin) in the same men, the
      plasma concentration of capsanthin ranged from 0.10 to 0.29 micromol/L at 8 h
      after ingestion. In contrast, the elevation of the plasma concentration of an
      acyclic hydrocarbon carotenoid, lycopene, by a single ingestion of tomato soup
      (equivalent to 186.3 micromol lycopene) in the same subjects was minimal (0.02
      0.06 micromol/L). The areas under the curves (AUC) for capsanthin between 0 and
      74 h and for lycopene between 0 and 72 h were 4.68 +/- 1.22 and 0.81 +/-
      0.17(micromol.h)/L, respectively. The half-lives (t1/2) were calculated to be
      20.1 +/- 1.3 and 222 +/- 15 h for capsanthin and lycopene, respectively. We
      conclude that the clearance of capsanthin is much faster than that of lycopene,
      although capsanthin is transported into plasma lipoproteins in larger amounts.
      This polar carotenoid may be metabolized in the human body more rapidly than
      lycopene. These data justify further research on the physiological functions of
      capsanthin and other xanthophylls.

PMID- 9237941
TI  - Dietary glucose is extensively recycled in the splanchnic bed of fed adult mice.
AB  - Quantification of the metabolism of dietary glucose by the splanchnic tissues is
      incomplete. Whether habitual carbohydrate intake affects splanchnic glucose
      metabolism is not known. Female mice were offered isoenergetic and isonitrogenous
      quantities of diets containing high (HCD) or low (LCD) amounts of carbohydrate,
      5% of which was [U-13C]-glucose. Four mice from each dietary group were killed
      after 24, 48 and 120 h. The 13C-isotopomer distribution in blood glucose, lactate
      and alanine and in hepatic alanine and glycogen was measured by selected ion
      monitoring mass spectrometry. [U-13C]-Glucose and its products, [U-13C]-lactate
      and alanine, were in complete isotopic equilibrium in the blood. The
      tracer:tracee ratio of hepatic [U-13C]-alanine was significantly higher (P <
      0.01) than that of circulating alanine. In both groups, the tracer:tracee ratio
      of circulating [U-13C]-glucose was significantly (P < 0.001) lower than that of
      the dietary carbohydrate, and the ratio of [13C3]-glucose:[U-13C]-glucose [0.57
      (HCD) and 0.78 (LCD); diet effect P < 0.05], a measure of glucose metabolic
      cycling, was between two- and fivefold higher than published values obtained with
      intravenous tracer glucose. The tracer:tracee ratio of [U-13C]-glycogen glucose
      was significantly (P < 0.05) higher than that of arterial glucose. We conclude
      the following: 1) dietary glucose is extensively recycled, via pyruvate, within
      the liver; 2) this metabolic cycle is maintained in mice consuming low
      carbohydrate diets; and 3) dietary carbohydrate is channelled to hepatic
      glycogen. We speculate that the metabolic cycling of enteral glucose is related
      to the hepatic catabolism of dietary protein.

PMID- 9237942
TI  - In vitro lactose fermentation by human colonic bacteria is modified by
      Lactobacillus acidophilus supplementation.
AB  - Adaptation of the colonic flora to lactose may contribute to lactose digestion in
      lactose maldigesters, and supplementation with Lactobacillus acidophilus may
      modify colonic fermentation of lactose and short-chain fatty acid production. We
      evaluated the capability of colonic bacteria to ferment lactose and the ability
      of L. acidophilus to modify lactose fermentation by the colonic microflora in
      vitro. An anaerobic continuous culture was established and inoculated with fresh
      samples of human feces. Lactose infusion was maintained at 25 g/d and pH at 6.7.
      L. acidophilus strain LA-1 (1.5 x 10(10) cells) was introduced into the fermenter
      on d 0 or added daily on d 0 through 4. The control was the continuous culture
      without the addition of lactobacilli. Rapid adaptation of colonic bacteria to
      lactose occurred within 1-2 d, with a significant decrease in lactose
      concentration and increase in beta-galactosidase activity, and lactose
      concentrations fell below 3 mmol/L by d 7. Supplementation with strain LA-1
      resulted in a significantly greater decrease in lactose concentration and greater
      increase in acetate and propionate production within the first day compared with
      the control group. However, there was no significant difference between the
      fermentation treated with L. acidophilus daily and the control after the first
      day. These data suggest that the colonic bacteria adapt quickly to lactose,
      causing efficient utilization of lactose. L. acidophilus supplementation may
      enhance lactose fermentation during early periods when the adaptation is not
      established in this model.

PMID- 9237943
TI  - Biliary excretion of biotin and biotin metabolites is quantitatively minor in
      rats and pigs.
AB  - We sought to determine whether the biliary excretion of biotin contributes
      substantially to the overall excretion of the vitamin in mammals, and hence,
      whether metabolism by gut microorganisms could account for some metabolism of
      biotin administered parenterally. [carbonyl-14C]Biotin was injected intravenously
      into six rats; bile and urine were collected for 24 h after injection. In a study
      of five pigs, serum and bile were analyzed for endogenous biotin and metabolites.
      In rat bile and urine, biotin, bisnorbiotin, biotin-d,l-sulfoxide, bisnorbiotin
      methyl ketone and two unidentified compounds were quantitated. In bile, these six
      compounds accounted for only 1.9 +/- 0.2% of the administered 14C, but in urine
      they accounted for 60.6 +/- 4.1%. The metabolite and time profiles in bile were
      also strikingly different from those in urine. Only biotin, bisnorbiotin and
      biotin-d,l-sulfoxide were quantitated in pig bile and serum. The concentrations
      of biotin, bisnorbiotin and biotin-d,l-sulfoxide in bile were 6.9-14.7 times the
      concentrations in serum. However, the bile to serum ratios of biotin and
      metabolites were >99% less than those of bilirubin, which is actively excreted.
      These data provide evidence that the biliary excretion of biotin and metabolites
      is quantitatively negligible.

PMID- 9237944
TI  - Dietary fiber influences nutrient utilization, growth and dry matter intake of
      green iguanas (Iguana iguana).
AB  - Herbivory is an uncommon feeding strategy in lizards. Appropriate diet
      formulations for captive lizards should be based on performance measures, yet few
      data are available on the effect of plant fiber on food intake, nutrient
      utilization and growth of captive herbivorous lizards. This study was conducted
      to determine the effect of three levels of dietary fiber on dry matter intake,
      nutrient and energy metabolizability and growth rate of the green iguana (Iguana
      iguana). Twenty-one captive iguanas were fed nutritionally complete diets
      containing three levels of dietary fiber: 19, 24, and 27% neutral detergent
      fiber. The iguanas were fed each diet for at least 12 wk, and total excreta were
      collected for 11.3 +/- 4.0 d (means +/- , range of 7 to 25 d). Diets and excreta
      were analyzed for dry matter, organic matter, gross energy, neutral detergent
      fiber, acid detergent fiber, and acid detergent lignin. The study was designed as
      a Latin square crossover. Across all diets, dry matter intake was proportional to
      body mass1.0 (BM). Growth rate was greater (P < 0. 05) when iguanas were fed the
      low and medium fiber diets (2.2 and 2. 4 g/d, respectively) than when fed the
      high fiber diet (1.4 g/d). However, mean daily dry matter intake of the three
      diets [7.2 g/(d. kg BM)] was not different. In general, digestibility of fiber
      fractions and the metabolizability of dietary energy decreased (P < 0.05) as the
      level of dietary fiber increased. These data suggest that a diet containing less
      than 27% neutral detergent fiber should be fed if rapid growth is to be sustained
      during intensive captive production of green iguanas.

PMID- 9237945
TI  - Pyridoxine-5'-beta--glucoside exhibits incomplete bioavailability as a source of
      vitamin B-6 and partially inhibits the utilization of co-ingested pyridoxine in
      humans.
AB  - This research was conducted to investigate 1) the bioavailability of pyridoxine
      5'-beta-D-glucoside (PN-glucoside) relative to that of pyridoxine (PN) in human
      subjects, and 2) the competitive effect of PN-glucoside on the metabolism of co
      ingested PN. To evaluate PN-glucoside bioavailability, the subjects were
      administered a single oral dose of either deuterium-labeled ([2H2]) PN (Trial 1)
      or [2H2] PN-glucoside (Trial 2), and the urinary excretion rates of labeled 4
      pyridoxic acid (4PA) were measured. The [2H2]4PA derived from [2H2] PN or [2H2]PN
      glucoside was excreted mainly in the first 8 h after the dose. Excretion of
      [2H2]4PA during the 48-h postdose period indicated that the bioavailability of PN
      glucoside was approximately 50% relative to PN, which is consistent with our
      previous report of 58% bioavailability determined using a different protocol and
      fewer subjects. To assess the effects of PN-glucoside on PN utilization, the
      subjects were administered different ratios of nonlabeled PN-glucoside with
      [2H2]PN in Trials 3 and 4. Comparing Trial 1 with Trials 3 and 4, the quantity of
      nonlabeled PN-glucoside, as a fraction of total vitamin B-6 administered, ranged
      from 0 to 40% (on the basis of pyridoxine equivalents), with a constant dose of
      [2H2]PN in each. In these trials, the rate but not the total extent of the
      excretion of [2H2]4PA derived from [2H2]PN was inversely related to the
      proportion of co-ingested nonlabeled PN-glucoside. Thus, antagonistic effects of
      PN-glucoside on PN metabolism do occur in humans, although the effect is less
      pronounced than that seen previously in rats. Such interactive effects must be
      considered in evaluating the net bioavailability of dietary forms of vitamin B-6.

PMID- 9237946
TI  - Vitamin C supplementation does not modify bone mineral content or mineral
      absorption in growing pigs.
AB  - We have demonstrated that alkaline phosphatase activity and collagen synthesis
      are dose-dependently stimulated by ascorbic acid in differentiated pig
      osteoblasts. In this study we further examined the relationship between ascorbic
      acid and bone metabolism by feeding young pigs large amounts of ascorbic acid.
      Three groups of seven 47-d-old pigs were given no ascorbic acid supplement
      (control), 500 (500 AA) or 1000 (1000 AA) mg ascorbic acid/kg diet for 4 mo.
      Calcium and P absorption and retention were evaluated by a 14-d balance trial
      immediately before killing in control and 1000 AA groups only (n = 6). Bones were
      collected at death and the bone ash and bending moment (three-point bending test)
      determined. Various plasma and urine indices of bone metabolism, especially those
      reflecting collagen degradation (hydroxyproline, deoxypyridinoline) and synthesis
      (carboxyterminal propeptide of type I collagen) were monitored. The plasma
      ascorbic acid concentrations increased with time and paralleled the dietary
      concentrations (P < 0.01). The Ca and P balances and the bone ash and bending
      moments in the ascorbic acid-supplemented pigs did not differ from those of the
      controls. Plasma osteocalcin was elevated (P < 0.05), whereas the other bone
      formation markers, alkaline phosphatase and carboxy terminal propeptide of type I
      collagen, were not affected by ascorbic acid. The plasma concentrations of Ca, P
      and 1,25-dihydroxycholecalciferol did not differ among the three groups. The
      unaffected urinary excretion of deoxypyridinoline and hydroxyproline in the
      ascorbic acid-supplemented pigs indicates that ascorbic acid does not alter bone
      resorption. Thus, high intakes of ascorbic acid have no positive influence on
      bone metabolism and bone characteristics in pigs. The in vivo long-term effects
      do not correlate with the short-term in vitro effects previously reported.

PMID- 9237948
TI  - Where to find nutritional science journals on the World Wide Web.
AB  - The World Wide Web (WWW) is a burgeoning information resource that can be
      utilized for current awareness and assistance in manuscript preparation and
      submission. The ever changing and expanding nature of the WWW allows it to
      provide up to the minute information, but this inherent changeability often makes
      information access difficult. To assist nutrition scientists in locating useful
      information about nutritional science journals on the WWW, this article
      critically reviews and describes the WWW sites for seventeen highly ranked
      nutrition and dietetics journals. Included in each annotation are the site's
      title, web address or Universal Resource Locator (URL), journal ranking and site
      authorship. Also listed is whether or not the site makes available the guidelines
      for authors, tables of contents, abstracts, online ordering, as well as
      information about the editorial board. This critical survey illustrates that the
      information on the web, regardless of its authority, is not of equal quality.

PMID- 9237949
TI  - Leptin involvement in reproductive performance.

PMID- 9237947
TI  - Evidence for histamine involvement in the effect of histidine loads on food and
      water intake in rats.
AB  - We examined the hypothesis that histidine is a regulator of short-term food and
      water intake in rats and that this control is through histidine's action as a
      precursor for histamine. The primary objectives were to measure food and water
      intake after histidine monohydrochloride monohydrate (His-HCl) given by
      intragastric (IG) and intraperitoneal (IP) routes of administration and to
      measure feeding and drinking responses to histidine when given after blockade of
      the histaminergic pathway by chlorpheniramine (CPA) and alpha
      fluoromethylhistidine (FMH). Eight experiments were conducted using a back-to
      back design. Rats were given treatment by IP or IG administration, and food and
      water intake was measured during time periods of 0-1, 1-2, 2-3 and 3-14 h.
      Histidine consistently reduced food intake with the sensitivity to IP much
      greater than to the IG route. The effect of histidine given by IP or IG on water
      intake was similar, generally causing an increase at least in the first hour.
      Histidine's action was not accounted for by its energy, pH or nitrogen content.
      Because FMH, which blocks the enzyme converting histidine to histamine, partially
      reversed the effect of histidine on food and water intake, these results support
      the hypothesis that histidine regulates food and water intake, at least in part,
      through its precursor control of histamine.

PMID- 9237950
TI  - Some vitamin sources relating to plasma homocysteine provide not only folate but
      also vitamins B-12 and B-6.

PMID- 9237952
TI  - Assessment of the nutritional effects of olestra, a nonabsorbed fat replacement:
      introduction and overview.
AB  - Olestra is a mixture of polyesters formed from sucrose and fatty acids derived
      from edible fats and oils. It is not absorbed or digested and can serve as a zero
      calorie replacement for dietary fat. Because olestra is lipophilic and not
      absorbed, it has the potential to interfere with the absorption of other dietary
      components, especially lipophilic ones, when it is in the digestive tract with
      those components. A series of studies were conducted in the domestic pig and in
      healthy adult humans to define the nature and extent of olestra's effect on fat
      soluble vitamins, selected water-soluble micronutrients, and macronutrients, and
      to demonstrate that the effects of olestra on the absorption of fat-soluble
      vitamins can be offset by adding extra amounts of the affected vitamins to
      olestra foods. Before conducting the human and pig studies, the intake of olestra
      from the consumption of snack foods made with olestra was estimated for various
      subgroups. The potential for olestra to affect the absorption of nonessential but
      potentially beneficial dietary phytochemicals was also assessed. In addition, an
      assessment of how consumption patterns influence the effect of olestra on the
      absorption of the highly lipophilic carotenoids was made. Finally, the results
      from the pig and human studies were used to assess the potential for olestra to
      affect the nutritional status of subgroups of the population who have
      particularly high nutrient needs or unique dietary patterns that may lead to
      large olestra-to-nutrient intake ratios.

PMID- 9237953
TI  - Estimated consumption and eating frequency of olestra from savory snacks using
      menu census data.
AB  - Potential chronic (14-d average) and acute (single-day) estimated daily intakes
      (EDI) were computed for olestra, a fat replacement intended for use in preparing
      savory snacks. The EDI were computed from eating occasions reported during a 14-d
      Menu Census survey among 4741 consumers; values were increased by 10% for
      conservatism. The eating occasions included all meals and in-between meal
      occasions eaten at home or away. Data from only those individuals who ate savory
      snacks at least once during the 14 d were used; this included 3820 individuals
      (81% of the sample) and represented a total of 16,067 eating days (24%
      frequency). The estimated mean chronic intake ranged from 1.8 to 4.7 g/d,
      depending on age and gender; at the 90th percentile, the range was 4.1-11.0 g/d.
      For all ages and both genders, the estimated mean intake was 3.1 g/d. Estimated
      acute intakes at the mean and 90th percentile ranged from 5.5 to 16.5 g/d and
      from 10.2 to 24.0 g/d, respectively, depending on age and gender. For all ages
      and both genders, the estimated mean intake was 10.2 g/d. The lack of parity in
      the chronic and acute intake estimates indicates that savory snacks are not eaten
      on a daily basis by the majority of snack eaters. The survey data were analyzed
      to understand the potential temporal eating patterns of olestra from savory
      snacks. When snacks were consumed, on average, 69% of the eating occasions were
      with main meals and 31% were between meals. Savory snacks did not contribute a
      major fraction of total food to the diet; only 7 and 18% of main meals contained
      a savory snack food at the 50th and 90th percentile, respectively. For the 50th
      percentile consumer (all ages, both genders), savory snacks were eaten four times
      during the 14-d survey period, and the eating occasions occurred on 3 d.
      Comparable results for 90th-percentile consumers were 10 eating occasions and 8
      eating days.

PMID- 9237954
TI  - The domestic pig as a model for evaluating olestra's nutritional effects.
AB  - Experimental conditions for measuring the effect of the noncaloric fat substitute
      olestra on the availability of dietary nutrients were established in the weanling
      domestic pig. To evaluate the tolerance of the pig for dietary fat levels similar
      to those in the human diet, groups were fed a standard corn-soy-based swine feed
      with and without 14% (30% of energy) added fat for 4 wk. To evaluate the adequacy
      of a purified diet to produce good growth, groups of pigs were fed purified diets
      providing 30% of energy from fat and micronutrients at 1, 1.3 or 1.6 times the
      NRC's requirements for 5- to 10-kg swine. Cumulative body weight gain, digestible
      feed efficiency and a lack of adverse effects showed that the pig can tolerate
      diets providing 30% of energy from fat and that a purified diet providing the
      NRC's requirements for micronutrients produces growth comparable to a
      nutritionally complete swine feed. To determine whether tissue concentrations of
      vitamins A, D, E and K in the pig respond to olestra and dietary concentrations
      of the vitamins, two groups were fed purified diet providing 1 or 1.6 times the
      NRC's requirements for micronutrients and 4.8% olestra. Significant increases
      occurred in the serum concentration of 25-hydroxyergocalciferol and liver
      concentrations of retinol and alpha-tocopherol with increasing dietary
      concentrations of the vitamins. Olestra reduced the tissue concentrations of
      vitamins A, D and E. Prothrombin time was not affected by dietary concentration
      of either phylloquinone or olestra. To determine the amount of UV light exposure
      required to produce 50-80% of vitamin D status from vitamin D3, a range typical
      of humans, two groups of pigs were fed the NRC requirement for vitamin D and
      exposed to 15 or 45 min/d of UV light. Serum concentration of 25
      hydroxycholecalciferol increased with increased exposure time. UV exposure of 1-2
      min/d was calculated to be sufficient to produce 50-80% of total vitamin D status
      from vitamin D3. No antemortem observations indicated an adverse olestra effect.

PMID- 9237955
TI  - Physical or temporal separation of olestra and vitamins A, E and D intake
      decreases the effect of olestra on the status of the vitamins in the pig.
AB  - A study was conducted in the domestic pig to determine 1 ) whether feeding
      olestra mixed in the diet exaggerated olestra effects on fat-soluble vitamin
      status compared with the effects of feeding it in a typical snack food, and 2)
      whether separating olestra consumption temporally from vitamin consumption
      affected the influence of olestra on vitamin status. Groups of 10 pigs each, five
      castrated males and five females, were fed 2.2% (wt/wt) olestra for 4 wk in
      purified diet that provided 1 time the National Research Council's requirements
      for swine of all micronutrients. The olestra was either mixed in the purified
      diet or fed in potato chips. The potato chips were given to the pigs at all three
      feedings, at the noon feeding only, or between the noon and the evening feedings.
      A control group was fed the purified diet with no olestra. The effects of olestra
      on indices of vitamin A, D and E status were from 1.7 to 4.5 times greater when
      olestra was fed three times daily mixed in the diet than when it was fed three
      times daily in potato chips. Because the effect of olestra on the status of the
      fat-soluble vitamins was diminished substantially by feeding the olestra in
      potato chips, it was not possible to conclude definitively how the temporal
      separation of olestra and vitamin consumption affected the olestra effect on
      vitamin status.

PMID- 9237956
TI  - Olestra dose response on fat-soluble and water-soluble nutrients in the pig.
AB  - Groups of weanling pigs were fed a purified diet containing graded concentrations
      of olestra ranging from 1.1 to 7.7% (wt/wt) and the NRC's requirements for
      micronutrients for 12 wk. Each group consisted of 12 pigs, with the exception of
      the control group, which had 20, with equal numbers of females and castrated
      males. The purpose of the study was to determine the dose-response effects of
      olestra on fat-soluble vitamins and selected water-soluble micronutrients. At wk
      0, 4, 8 and 12, hematology, clinical chemistry and blood concentrations of
      vitamins A, E, K and B12, and 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D,
      folate, calcium, iron, zinc and adipose concentration of vitamin E were measured.
      Cumulative weight gain and feed efficiency were determined weekly. Prothrombin
      time was measured weekly for the control group and the groups fed 5.5 or 7.7%
      olestra, and monthly for other groups. Liver concentrations of vitamins A, E, and
      B12 and iron and bone concentrations of calcium, phosphorus, zinc and ash were
      measured for 12 pigs killed at wk 0 and for all animals at wk 12. By wk 12, the
      pigs were eating from 20 to 155 g/d of olestra. Olestra did not affect the pigs'
      growth or feed efficiency, indicating that the digestion and absorption of
      macronutrients were unaffected. Olestra reduced tissue concentrations of vitamin
      A, vitamin E and 25-hydroxyergocalciferol in a dose-responsive manner but did not
      affect prothrombin time. Olestra had no effect on the status of folate, vitamin
      B12, zinc or iron. Statistically reduced liver concentrations of vitamin B12 and
      iron in groups fed 5.5 or 7.7% olestra and a significant trend in bone ash
      content with olestra intake were possibly due to the poor vitamin A and/or
      vitamin E status of the pigs.

PMID- 9237957
TI  - Olestra's effect on the status of vitamins A, D and E in the pig can be offset by
      increasing dietary levels of these vitamins.
AB  - Groups of weanling pigs (5 castrated males, 5 females per group) were fed
      purified diets containing the NRC's requirements for nutrients and 0, 1.1, 4.4 or
      7.7% olestra for 12 wk. Graded concentrations of vitamins A, D2 and E were added
      at each olestra concentration. The primary purpose of the study was to establish
      relationships between dietary concentration of olestra and the amounts of
      vitamins A, D2 and E needed to restore tissue concentrations of these vitamins to
      control concentrations. A secondary purpose was to confirm that olestra does not
      affect the status of vitamin K or water-soluble nutrients. Liver concentrations
      of vitamins A, E and B12, iron and zinc and bone concentrations of ash, zinc,
      calcium and phosphorus, were measured in a group of pigs killed at the start of
      the study and in all pigs killed at wk 12. Growth, feed efficiency, hematology,
      clinical chemistry, blood concentrations of retinol, alpha-tocopherol, 25
      hydroxyergocalciferol, 25-hydroxycholecalciferol, 1,25-dihydroxyvitamin D,
      folate, iron, total iron-binding capacity, zinc and calcium and adipose
      concentration of vitamin E were measured at 4-wk intervals. Prothrombin time was
      measured weekly for the control and 7.7% olestra groups, monthly for others.
      Relationships derived from measured tissue concentrations of vitamins A and E
      showed that constant amounts of the vitamins were required per unit mass of
      olestra in the diet to restore tissue concentrations to control values. Such a
      relationship could not be determined for vitamin D because exposure of the pigs
      to UV light resulted in an apparent interaction between vitamin D2 and vitamin
      D3. Olestra did not affect growth, digestible feed efficiency, vitamin K status
      or the status of the water-soluble micronutrients, in agreement with other
      studies in the pig.

PMID- 9237959
TI  - Nutritional status of pigs fed olestra with and without increased dietary levels
      of vitamins A and E in long-term studies.
AB  - In a 26-wk study, five groups (n = 10) of domestic pigs were fed 0.25, 0.5, 1.1,
      3.3 or 5.5% olestra; three groups were fed 0.25% with graded levels of vitamins A
      and E; and one group was fed 5.5% with added vitamins A and E and exposed to UV
      light. In a 39-wk study, two groups (n = 10) were fed 0.25% olestra with or
      without added vitamins A and E. In each study, a control group was fed basal diet
      with no olestra, and a group was killed at d 0 for base-line nutrient
      measurements. The diets provided the NRC's requirements of micronutrients for 5-
      to 10-kg pigs, with the following two exceptions: vitamin D was provided at twice
      the requirement in the 26-wk study and vitamin K was provided at 20% of the
      requirement in the 39-wk study. One purpose of the studies was to determine the
      amounts of vitamins A and E required to restore tissue concentrations of those
      vitamins to control concentrations. A second purpose was to determine the effects
      of olestra on the status of vitamins A, D, E, K and B12, and folate, iron,
      calcium and zinc when pigs eat olestra at intakes similar to estimated human
      intake for a period covering major growth and developmental phases, including
      sexual maturation. Olestra reduced tissue concentrations of vitamins A, D and E
      but did not affect prothrombin time or the status of the water-soluble nutrients.
      The amount of vitamin A required to restore liver concentration to control
      concentration was 93 microg retinyl palmitate/g olestra. Restoration levels for
      serum and liver concentrations of vitamin E were 2.2 and 2.1 mg d-alpha
      tocopheryl acetate/g olestra. Olestra did not affect growth or digestible feed
      efficiency in either study, indicating that the absorption and utilization of
      macronutrients were unaffected. There were no antemortem observations or changes
      in clinical chemistry or hematology that would indicate an adverse effect of
      olestra.

PMID- 9237960
TI  - Olestra affects serum concentrations of alpha-tocopherol and carotenoids but not
      vitamin D or vitamin K status in free-living subjects.
AB  - Normal, healthy, free-living adults ingested either 18 g/d olestra, with or
      without 1.1 mg tocopheryl acetate/g olestra, or 18 g/d triglyceride placebo, for
      16 wk in a double-blind, placebo-controlled study. Serum concentrations of alpha
      tocopherol, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, retinol
      and cholesterol were measured biweekly. Serum 25-hydroxyvitamin D concentration,
      prothrombin time, partial thromboplastin time and plasma concentration of
      functional prothrombin (Simplastin-Ecarin assay) were measured at wk 0, 8 and 16.
      Relative to the placebo group, serum alpha-tocopherol concentration was reduced
      6% for the group given 18 g/d olestra. Addition of tocopheryl acetate to olestra
      partially offset the effect of olestra. For the group given 18 g/d olestra plus
      1.1 mg tocopheryl acetate/g olestra, serum alpha-tocopherol concentration was 4%
      less than the placebo value. Olestra reduced serum concentration of beta-carotene
      by 27%; the other carotenoids were similarly affected. Serum cholesterol
      concentration was reduced approximately 4.5% in the olestra groups, relative to
      placebo, but the differences were not significant. Serum triglycerides, serum 25
      hydroxyvitamin D, prothrombin time, partial thromboplastin time or the plasma
      concentration of under-gamma-carboxylated prothrombin were unaffected by olestra.
      Clinical observations and laboratory measures indicated no health-related effects
      of olestra; mild-to-moderate transient gastrointestinal symptoms such as
      bloating, cramping, loose stools and diarrhea were reported by all groups.

PMID- 9237962
TI  - Olestra's effect on vitamins D and E in humans can be offset by increasing
      dietary levels of these vitamins.
AB  - One hundred two normal healthy males and females were given 0, 8, 20 or 32 g/d
      olestra to which had been added graded amounts of vitamins A, D and E for 8 wk in
      a parallel, double-blind study. The primary purpose of the study was to determine
      the amounts of vitamins D and E needed to offset the effect of olestra on the
      availability of these vitamins. Serum concentrations of retinol, carotenoids, 25
      hydroxyvitamin D metabolites, alpha-tocopherol, phylloquinone, lipids, ferritin
      and total iron, iron-binding capacity and hematology parameters, plasma
      concentrations of des-gamma-carboxyprothrombin and prothrombin, and urinary gamma
      carboxyglutamic acid (Gla) excretion were measured biweekly. Clinical chemistry
      and urinalysis parameters, vitamin B12 absorption, and serum 1,25
      dihydroxyvitamin D concentration were measured at wk 0 and 8. Serum
      concentrations of alpha-tocopherol and 25-hydroxyergocalciferol were restored to
      control concentration by adding 2.1 mg d-alpha-tocopheryl acetate and 0.06 microg
      ergocalciferol per gram of olestra, respectively, to the diet. Olestra reduced
      serum concentrations of 25-hydroxyergocalciferol, carotenoids and phylloquinone
      in a dose-responsive manner but did not affect Gla excretion, plasma des-gamma
      carboxyprothrombin and prothrombin concentrations, overall vitamin D status,
      vitamin B12 absorption or iron status. Laboratory evaluations showed no olestra
      related effects. Subjects in all groups reported mild to moderately severe
      transient gastrointestinal symptoms. These symptoms did not affect study
      compliance or the integrity of the data.

PMID- 9237961
TI  - Olestra dose response on fat-soluble and water-soluble nutrients in humans.
AB  - Ninety normal healthy adults were given 0, 8, 20 or 32 g/d olestra for 8 wk as
      part of a diet that provided 1 +/- 0.2 of the recommended dietary allowance (RDA)
      of vitamins A, D, E and K, folate zinc, calcium and iron. In addition, a 20
      microg/d supplement of vitamin D was supplied. The diet provided 15% of energy
      from protein, 35% from fat and 55% from carbohydrate. The purpose of the study
      was to determine the dose response of olestra on vitamins D, E and K,
      carotenoids, vitamin B12, folate and zinc. Circulating concentrations of retinol,
      carotenoids, tocopherols, 25-hydroxy- and 1,25-dihydroxyvitamin D metabolites,
      phylloquinone, des-gamma-carboxyprothrombin, prothrombin, folate and
      hematological parameters were measured biweekly, as were urine concentrations of
      zinc and gamma-carboxyglutamic acid (Gla). Clinical chemistry, urinalysis and
      vitamin B12 absorption were measured at wk 0 and 8. Olestra reduced serum
      concentrations of carotenoids, alpha-tocopherol, 25-hydroxyergocalciferol and
      phylloquinone in a dose-responsive manner. Olestra did not affect Gla excretion,
      plasma des-gamma-carboxyprothrombin or prothrombin concentrations, prothrombin
      time, vitamin B12 absorption, overall vitamin D status or the status of folate or
      zinc. Laboratory evaluations showed no health-related effects of olestra.
      Subjects in all groups reported common gastrointestinal symptoms such as loose
      stools, fecal urgency and flatulence, which were transient and generally mild to
      moderate in severity. These symptoms did not affect protocol compliance or the
      ability to measure the potential for olestra to affect nutrient availability.

PMID- 9237963
TI  - Olestra ingestion and retinyl palmitate absorption in humans.
AB  - This study examined the effect of olestra, a zero-calorie fat replacement, on the
      absorption of retinyl palmitate in humans. After a 30-d adaptation period during
      which they consumed 10 g olestra/d in potato chips under free-living conditions,
      68 healthy male subjects were housed in a metabolic ward and given a single dose
      of retinyl palmitate (0.33 RDA) containing a trace amount of 3H-retinyl palmitate
      with a breakfast that contained 0, 8, 20 or 32 g of olestra and about 38 g of
      triglyceride. Blood was collected at defined intervals for 48 h and plasma
      analyzed for 3H-retinyl esters by HPLC and liquid scintillation spectrometry.
      There was no significant effect on retinyl palmitate absorption as determined
      from the area under the plasma 3H-retinyl esters concentration-time curve.
      However, an area under the plasma concentration-time curve in the 32-g olestra
      group that was 81% (mean value) or 70% (median value) of the area under the curve
      for the placebo group suggested that olestra may have affected retinyl palmitate
      absorption. Inclusion or exclusion of 13 high responders did not change the
      results.

PMID- 9237964
TI  - Olestra ingestion and dietary fat absorption in humans.
AB  - The effect of olestra, a zero-calorie fat replacement, on the absorption of
      dietary fat was determined with a dual-isotope technique in 67 healthy male
      subjects. After a 30-d adaptation period in which they consumed potato chips
      which delivered either 10 g/d olestra or 10 g/d triglyceride under free-living
      conditions, the subjects were housed in a metabolic ward and given 0, 8, 20 or 32
      g olestra in potato chips. The chips were eaten as part of a breakfast containing
      about 38 g of fat, about 0.16 mg of 14C-triolein, and a nonabsorbable marker,
      51CrCl3. Feces were collected for 7 d, and aliquots of the two daily collections
      containing the highest levels of 51Cr were oxidized. The CO2 was collected, and
      14C content was determined by liquid scintillation spectrometry. The fractional
      absorption of 14C-triolein was calculated from the average ratios of 14C/51Cr
      dosed and measured in the feces. Olestra had a slight but significant dose
      response effect on triglyceride absorption: the highest olestra dose (32 g)
      reduced absorption by 1.2%. This effect is not nutritionally significant with
      respect to either availability of essential fatty acids or energy intake.

PMID- 9237965
TI  - Evaluation of the potential for olestra to affect the availability of dietary
      phytochemicals.
AB  - It has been hypothesized that phytochemicals found in fruits and vegetables are
      responsible for the inverse association observed between diets high in fruits and
      vegetables and risk of certain chronic diseases and cancer. This paper assesses
      the potential for olestra to affect the absorption of dietary phytochemicals and
      estimates the effect of olestra on the availability of carotenoids when olestra
      containing snacks and foods containing carotenoids are eaten in free-living
      diets. Experimental data compiled on the effects of olestra on the availability
      of 29 compounds, mainly nutrients and oral medications, showed that olestra
      affects the availability of only molecules having octanol-water partition
      coefficients greater than approximately 7.5. Partition coefficients compiled for
      382 dietary phytochemicals showed that only two classes of phytochemicals,
      phytosterols and carotenoids, contain molecules with octanol-water partition
      coefficients in the range in which olestra could potentially affect
      bioavailability. The potential effect on the bioavailability of phytosterols
      would be <10% and would not be expected to be of concern inasmuch as the
      hypothesized benefit of consuming pharmacological amounts of phytosterols is to
      reduce cholesterol availability, a function also of olestra. A 5.9% reduction in
      the average effective beta-carotene intake was calculated for individuals eating
      olestra-containing snack foods in free-living diets. The calculation was made by
      assuming that carotenoid bioavailability would be reduced to the extent measured
      in human clinical studies each time olestra-containing snacks and carotenoid
      containing foods are eaten together and that all snacks eaten are made with
      olestra. Among individuals with low carotenoid intakes (the lowest 10%) the
      calculated reduction was 6.0%; for heavy snack eaters (the top 10%) it was 9.5%.
      These effects on carotenoid bioavailability are similar to those that can occur
      with other dietary factors.

PMID- 9237966
TI  - An indirect means of assessing potential nutritional effects of dietary olestra
      in healthy subgroups of the general population.
AB  - The potential for olestra to affect the absorption of dietary components was
      measured in 18- to 44-y-old humans and the weanling pig. Results from the studies
      were assessed to determine if they were relevant to subgroups of the population
      not included in the studies. Hypothetrically, two factors that might cause the
      study results not to be relevant to certain subgroups are dietary pattern and
      metabolic need. A dietary pattern resulting in olestra-to-nutrient intake ratios
      greater than those tested in the studies might produce effects greater than those
      measured. Metabolic needs (i.e., nutrient requirements) among subgroups greater
      than those of the study population might mean that any effects on nutrient
      absorption seen in the studies would be larger among subgroups. If olestra-to
      nutrient ratios and nutrient requirements of a subgroup were less than those
      covered in the studies, then the effects of olestra on the nutritional status of
      the subgroup should be no different than the effects measured in the studies.
      Subgroups with high olestra-to-nutrient intake ratios were identified by
      calculating the ratios for those nutrients assessed in the studies [i.e.,
      macronutrients, vitamins A (including beta-carotene), D, E and K, folate, vitamin
      B12, calcium, iron and zinc]. Subgroups with the greatest olestra-to-nutrient
      intake ratios for one or more nutrients included children, teenagers and young
      adults, women from low income families and vegetarians. Subgroups with the
      greatest metabolic need for one or more nutrients included children, teenagers,
      and pregnant and lactating women. The olestra-to-nutrient ratios and nutrient
      requirements of the subgroups having the greatest ratios and requirements were
      compared with those of the test population. The olestra-to-nutrient intake ratios
      fed in the studies were greater than those for any subgroup for all nutrients
      except calcium, which is not affected by olestra. Metabolic needs of the test
      population were greater than those of all population subgroups for all nutrients.
      The effects of olestra on nutritional status should not be different or greater
      than those measured in the controlled clinical tests for subgroups not directly
      tested.

PMID- 9237967
TI  - Assessment of the nutritional effects of olestra, a nonabsorbed fat replacement:
      summary.
AB  - Olestra is a zero-calorie fat replacement intended to replace 100% of the fat
      used in the preparation of savory snacks. Olestra can affect the absorption of
      other dietary components, especially highly lipophilic ones, when ingested at the
      same time. The potential effects of olestra on the absorption of essential fat
      soluble and water-soluble dietary components have been investigated in pigs and
      in humans. In these studies, subjects were fed daily amounts of olestra up to 10
      times the estimated mean intake from savory snacks and the olestra was eaten each
      day of the studies. In real life, snacks are eaten on average five times in a 14
      d period. Olestra did not affect the availability of water-soluble micronutrients
      or the absorption and utilization of macronutrients. Olestra reduced the
      absorption of fat-soluble vitamins A, D, E and K; however, the effects can be
      offset by adding specified amounts of the vitamins to olestra foods. Olestra also
      reduced the absorption of carotenoids; analysis of dietary patterns showed that
      in real life the reduction will likely be <10%. Any effect on vitamin A stores
      caused by a reduction in carotenoid uptake is offset by the addition of vitamin A
      to olestra foods. Because of the olestra-to-nutrient ratios fed and the
      nutritional requirements of the test subjects, the effects of olestra on
      nutritional status of subgroups of the population are unlikely to be different
      than those measured in the studies. An analysis of lipophilicity showed that
      olestra is unlikely to significantly affect the uptake of potentially beneficial
      phytochemicals from fruits and vegetables. Some people eating large amounts of
      olestra snacks may experience common GI symptoms such as stomach discomfort or
      changes in stool consistency, similar to symptoms accompanying other dietary
      changes. These symptoms present no health risks.

PMID- 9237985
TI  - The high spontaneous mutation rate: is it a health risk?
AB  - The human mutation rate for base substitutions is much higher in males than in
      females and increases with paternal age. This effect is mainly, if not entirely,
      due to the large number of cell divisions in the male germ line. The mutation
      rate increase is considerably greater than expected if the mutation rate were
      simply proportional to the number of cell divisions. In contrast, those mutations
      that are small deletions or rearrangements do not show the paternal age effect.
      The observed increase with the age of the father in the incidence of children
      with different dominant mutations is variable, presumably the result of different
      mixtures of base substitutions and deletions. In Drosophila, the rate of
      mutations causing minor deleterious effects is estimated to be about one new
      mutation per zygote. Because of a larger number of genes and a much larger amount
      of DNA, the human rate is presumably higher. Recently, the Drosophila data have
      been reanalyzed and the mutation-rate estimate questioned, but I believe that the
      totality of evidence supports the original conclusion. The most reasonable way in
      which a species can cope with a high mutation rate is by quasi-truncation
      selection, whereby a number of mutant genes are eliminated by one "genetic
      death."

PMID- 9237987
TI  - Enhanced methionine levels and increased nutritive value of seeds of transgenic
      lupins (Lupinus angustifolius L.) expressing a sunflower seed albumin gene.
AB  - With the aim of improving the nutritive value of an important grain legume crop,
      a chimeric gene specifying seed-specific expression of a sulfur-rich, sunflower
      seed albumin was stably transformed into narrow-leafed lupin (Lupinus
      angustifolius L.). Sunflower seed albumin accounted for 5% of extractable seed
      protein in a line containing a single tandem insertion of the transferred DNA.
      The transgenic seeds contained less sulfate and more total amino acid sulfur than
      the nontransgenic parent line. This was associated with a 94% increase in
      methionine content and a 12% reduction in cysteine content. There was no
      statistically significant change in other amino acids or in total nitrogen or
      total sulfur contents of the seeds. In feeding trials with rats, the transgenic
      seeds gave statistically significant increases in live weight gain, true protein
      digestibility, biological value, and net protein utilization, compared with wild
      type seeds. These findings demonstrate the feasibility of using genetic
      engineering to improve the nutritive value of grain crops.

PMID- 9237988
TI  - Measurements of attractive forces between proteins and end-grafted poly(ethylene
      glycol) chains.
AB  - The surface force apparatus was used to measure directly the molecular forces
      between streptavidin and lipid bilayers displaying grafted Mr 2,000 poly(ethylene
      glycol) (PEG). These measurements provide direct evidence for the formation of
      relatively strong attractive forces between PEG and protein. At low compressive
      loads, the forces were repulsive, but they became attractive when the proteins
      were pressed into the polymer layer at higher loads. The adhesion was
      sufficiently robust that separation of the streptavidin and PEG uprooted anchored
      polymer from the supporting membrane. These interactions altered the properties
      of the grafted chains. After the onset of the attraction, the polymer continued
      to bind protein for several hours. The changes were not due to protein
      denaturation. These data demonstrate directly that the biological activity of PEG
      is not due solely to properties of simple polymers such as the excluded volume.
      It is also coupled to the competitive interactions between solvent and other
      materials such as proteins for the chain segments and to the ability of this
      material to adopt higher order intrachain structures.

PMID- 9237989
TI  - Monitoring protein-protein interactions in intact eukaryotic cells by beta
      galactosidase complementation.
AB  - We present an approach for monitoring protein-protein interactions within intact
      eukaryotic cells, which should increase our understanding of the regulatory
      circuitry that controls the proliferation and differentiation of cells and how
      these processes go awry in disease states such as cancer. Chimeric proteins
      composed of proteins of interest fused to complementing beta-galactosidase (beta
      gal) deletion mutants permit a novel analysis of protein complexes within cells.
      In this approach, the beta-gal activity resulting from the forced interaction of
      nonfunctional weakly complementing beta-gal peptides (Deltaalpha and Deltaomega)
      serves as a measure of the extent of interaction of the non-beta-gal portions of
      the chimeras. To test this application of lacZ intracistronic complementation,
      proteins that form a complex in the presence of rapamycin were used. These
      proteins, FRAP and FKBP12, were synthesized as fusion proteins with Deltaalpha
      and Deltaomega, respectively. Enzymatic beta-gal activity served to monitor the
      formation of the rapamycin-induced chimeric FRAP/FKBP12 protein complex in a time
      and dose-dependent manner, as assessed by histochemical, biochemical, and
      fluorescence-activated cell sorting assays. This approach may prove to be a
      valuable adjunct to in vitro immunoprecipitation and crosslinking methods and in
      vivo yeast two-hybrid and fluorescence energy transfer systems. It may also allow
      a direct assessment of specific protein dimerization interactions in a
      biologically relevant context, localized in the cell compartments in which they
      occur, and in the milieu of competing proteins.

PMID- 9237990
TI  - Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN
      and FAD-containing enzymes.
AB  - Microsomal NADPH-cytochrome P450 reductase (CPR) is one of only two mammalian
      enzymes known to contain both FAD and FMN, the other being nitric-oxide synthase.
      CPR is a membrane-bound protein and catalyzes electron transfer from NADPH to all
      known microsomal cytochromes P450. The structure of rat liver CPR, expressed in
      Escherichia coli and solubilized by limited trypsinolysis, has been determined by
      x-ray crystallography at 2.6 A resolution. The molecule is composed of four
      structural domains: (from the N- to C- termini) the FMN-binding domain, the
      connecting domain, and the FAD- and NADPH-binding domains. The FMN-binding domain
      is similar to the structure of flavodoxin, whereas the two C-terminal
      dinucleotide-binding domains are similar to those of ferredoxin-NADP+ reductase
      (FNR). The connecting domain, situated between the FMN-binding and FNR-like
      domains, is responsible for the relative orientation of the other domains,
      ensuring the proper alignment of the two flavins necessary for efficient electron
      transfer. The two flavin isoalloxazine rings are juxtaposed, with the closest
      distance between them being about 4 A. The bowl-shaped surface near the FMN
      binding site is likely the docking site of cytochrome c and the physiological
      redox partners, including cytochromes P450 and b5 and heme oxygenase.

PMID- 9237991
TI  - Non-enzymatic and enzymatic hydrolysis of alkyl halides: a haloalkane
      dehalogenation enzyme evolved to stabilize the gas-phase transition state of an
      SN2 displacement reaction.
AB  - The semiempirical PM3 method, calibrated against ab initio HF/6-31+G(d) theory,
      has been used to elucidate the reaction of 1, 2-dichloroethane (DCE) with the
      carboxylate of Asp-124 at the active site of haloalkane dehalogenase of
      Xanthobacter autothropicus. Asp-124 and 13 other amino acid side chains that make
      up the active site cavity (Glu-56, Trp-125, Phe-128, Phe-172, Trp-175, Leu-179,
      Val-219, Phe-222, Pro-223, Val-226, Leu-262, Leu-263, and His-289) were included
      in the calculations. The three most significant observations of the present study
      are that: (i) the DCE substrate and Asp-124 carboxylate, in the reactive ES
      complex, are present as an ion-molecule complex with a structure similar to that
      seen in the gas-phase reaction of AcO- with DCE; (ii) the structures of the
      transition states in the gas-phase and enzymatic reaction are much the same where
      the structure formed at the active site is somewhat exploded; and (iii) the
      enthalpies in going from ground states to transition states in the enzymatic and
      gas-phase reactions differ by only a couple kcal/mol. The dehalogenase derives
      its catalytic power from: (i) bringing the electrophile and nucleophile together
      in a low-dielectric environment in an orientation that allows the reaction to
      occur without much structural reorganization; (ii) desolvation; and (iii)
      stabilizing the leaving chloride anion by Trp-125 and Trp-175 through hydrogen
      bonding.

PMID- 9237992
TI  - A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA
      adenosine deaminase.
AB  - Editing of RNA changes the read-out of information from DNA by altering the
      nucleotide sequence of a transcript. One type of RNA editing found in all
      metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the
      deamination of adenosine to give inosine, which is translated as guanosine.
      Editing thus allows variant proteins to be produced from a single pre-mRNA. A
      mechanism by which dsRNA substrates form is through pairing of intronic and
      exonic sequences before the removal of noncoding sequences by splicing. Here we
      report that the RNA editing enzyme, human dsRNA adenosine deaminase (DRADA1, or
      ADAR1) contains a domain (Zalpha) that binds specifically to the left-handed Z
      DNA conformation with high affinity (KD = 4 nM). As formation of Z-DNA in vivo
      occurs 5' to, or behind, a moving RNA polymerase during transcription,
      recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can
      be targeted to a nascent RNA so that editing occurs before splicing. Analysis of
      sequences related to Zalpha has allowed identification of motifs common to this
      class of nucleic acid binding domain.

PMID- 9237993
TI  - Purification and characterization of a CENP-B homologue protein that binds to the
      centromeric K-type repeat DNA of Schizosaccharomyces pombe.
AB  - We have purified and characterized a novel 60-kDa protein that binds to
      centromeric K-type repeat DNA from Schizosaccharomyces pombe. This protein was
      initially purified by its ability to bind to the autonomously replicating
      sequence 3002 DNA. Cloning of the gene encoding this protein revealed that it
      possesses significant homology to the mammalian centromere DNA-binding protein
      CENP-B and S. pombe Abp1, and this gene was designated as cbh+ (CENP-B
      homologue). Cbh protein specifically interacts in vitro with the K-type repeat
      DNA, which is essential for centromere function. The Cbh-binding consensus
      sequence was determined by DNase I footprinting assays as PyPuATATPyPuTA,
      featuring an inverted repeat of the first four nucleotides. Based on its binding
      activity to centromeric DNA and homology to centromere proteins, we suggest that
      this protein may be a functional homologue of the mammalian CENP-B in S. pombe.

PMID- 9237994
TI  - Preferential interaction of the his pause RNA hairpin with RNA polymerase beta
      subunit residues 904-950 correlates with strong transcriptional pausing.
AB  - RNA secondary structures (hairpins) that form as the nascent RNA emerges from RNA
      polymerase are important components of many signals that regulate transcription,
      including some pause sites, all rho-independent terminators, and some
      antiterminators. At the his leader pause site, a 5-bp-stem, 8-nt-loop pause RNA
      hairpin forms 11 nt from the RNA 3' end and stabilizes a transcription complex
      conformation slow to react with NTP substrate. This stabilization appears to
      depend at least in part on an interaction with RNA polymerase. We tested for RNA
      hairpin interaction with the paused polymerase by crosslinking 5-iodoUMP
      positioned specifically in the hairpin loop. In the paused conformation, strong
      and unusual crosslinking of the pause hairpin to beta904-950 replaced
      crosslinking to beta' and to other parts of beta that occurred in nonpaused
      complexes prior to hairpin formation. These changes in nascent RNA interactions
      may inhibit reactive alignment of the RNA 3' end in the paused complex and be
      related to events at rho-independent terminators.

PMID- 9237995
TI  - The Bacillus subtilis crh gene encodes a HPr-like protein involved in carbon
      catabolite repression.
AB  - Carbon catabolite repression (CCR) of several Bacillus subtilis catabolic genes
      is mediated by ATP-dependent phosphorylation of histidine-containing protein
      (HPr), a phosphocarrier protein of the phosphoenolpyruvate (PEP): sugar
      phosphotransferase system. In this study, we report the discovery of a new B.
      subtilis gene encoding a HPr-like protein, Crh (for catabolite repression HPr),
      composed of 85 amino acids. Crh exhibits 45% sequence identity with HPr, but the
      active site His-15 of HPr is replaced with a glutamine in Crh. Crh is therefore
      not phosphorylated by PEP and enzyme I, but is phosphorylated by ATP and the HPr
      kinase in the presence of fructose-1,6-bisphosphate. We determined Ser-46 as the
      site of phosphorylation in Crh by carrying out mass spectrometry with peptides
      obtained by tryptic digestion or CNBr cleavage. In a B. subtilis ptsH1 mutant
      strain, synthesis of beta-xylosidase, inositol dehydrogenase, and levanase was
      only partially relieved from CCR. Additional disruption of the crh gene caused
      almost complete relief from CCR. In a ptsH1 crh1 mutant, producing HPr and Crh in
      which Ser-46 is replaced with a nonphosphorylatable alanyl residue, expression of
      beta-xylosidase was also completely relieved from glucose repression. These
      results suggest that CCR of certain catabolic operons requires, in addition to
      CcpA, ATP-dependent phosphorylation of Crh, and HPr at Ser-46.

PMID- 9237996
TI  - In vivo kinetics of a redox-regulated transcriptional switch.
AB  - SoxR is a transcription activator governing a cellular response to superoxide and
      nitric oxide in Escherichia coli. SoxR protein is a homodimer, and each monomer
      has a redox-active [2Fe-2S] cluster. Oxidation and reduction of the [2Fe-2S]
      clusters can reversibly activate and inactivate SoxR transcriptional activity.
      Here, we use electron paramagnetic resonance spectroscopy to follow the redox
      switching process of SoxR protein in vivo. SoxR [2Fe-2S] clusters were in the
      fully reduced state during normal aerobic growth, but were completely oxidized
      after only 2-min aerobic exposure of the cells to superoxide-generating agents
      such as paraquat. The oxidized SoxR [2Fe-2S] clusters were rapidly re-reduced in
      vivo once the oxidative stress was removed. The in vivo kinetics of SoxR [2Fe-2S]
      cluster oxidation and reduction exactly paralleled the increase and decrease of
      transcription of soxS, the target gene for SoxR. The kinetic analysis also
      revealed that an oxidative stress-linked decrease in soxS mRNA stability
      contributes to the rapid attainment of a new steady state after SoxR activation.
      Such a redox stress-related change in soxS mRNA stability may represent a new
      level of biological control.

PMID- 9237998
TI  - Purification and characterization of acetone carboxylase from Xanthobacter strain
      Py2.
AB  - Acetone metabolism in the aerobic bacterium Xanthobacter strain Py2 proceeds by a
      carboxylation reaction forming acetoacetate as the first detectable product. In
      this study, acetone carboxylase, the enzyme catalyzing this reaction, has been
      purified to homogeneity and characterized. Acetone carboxylase was comprised of
      three polypeptides with molecular weights of 85,300, 78,300, and 19,600 arranged
      in an alpha2beta2gamma2 quaternary structure. The carboxylation of acetone was
      coupled to the hydrolysis of ATP and formation of 1 mol AMP and 2 mol inorganic
      phosphate per mol acetoacetate formed. ADP was also formed during the course of
      acetone consumption, but only accumulated at low, substoichiometric levels (
      approximately 10% yield) relative to acetoacetate. Inorganic pyrophosphate could
      not be detected as an intermediate or product of acetone carboxylation. In the
      absence of CO2, acetone carboxylase catalyzed the acetone-dependent hydrolysis of
      ATP to form both ADP and AMP, with ADP accumulating to higher levels than AMP
      during the course of the assays. Acetone carboxylase did not have inorganic
      pyrophosphatase activity. Acetone carboxylase exhibited a Vmax for acetone
      carboxylation of 0.225 micromol acetoacetate formed min-1.mg-1 at 30 degrees C
      and pH 7.6 and apparent Km values of 7.80 microM (acetone), 122 microM (ATP), and
      4. 17 mM (CO2 plus bicarbonate). These studies reveal molecular properties of the
      first bacterial acetone-metabolizing enzyme to be isolated and suggest a novel
      mechanism of acetone carboxylation coupled to ATP hydrolysis and AMP and
      inorganic phosphate formation.

PMID- 9237997
TI  - Structural flexibility in transcription complex formation revealed by protein-DNA
      photocrosslinking.
AB  - The Oct-1 POU domain binds diverse DNA-sequence elements and forms a higher-order
      regulatory complex with the herpes simplex virus coregulator VP16. The POU domain
      contains two separate DNA-binding domains joined by a flexible linker. By protein
      DNA photocrosslinking we show that the relative positioning of the two POU DNA
      binding domains on DNA varies depending on the nature of the DNA target. On a
      single VP16-responsive element, the POU domain adopts multiple conformations. To
      determine the structure of the Oct-1 POU domain in a multiprotein complex with
      VP16, we allowed VP16 to interact with previously crosslinked POU-domain-DNA
      complexes and found that VP16 can associate with multiple POU-domain
      conformations. These results reveal the dynamic potential of a DNA-binding domain
      in directing transcriptional regulatory complex formation.

PMID- 9238000
TI  - Phenotypic conversion of drug-resistant bacteria to drug sensitivity.
AB  - Plasmids that contain synthetic genes coding for small oligoribonucleotides
      called external guide sequences (EGSs) have been introduced into strains of
      Escherichia coli harboring antibiotic resistance genes. The EGSs direct RNase P
      to cleave the mRNAs transcribed from these genes thereby converting the phenotype
      of drug-resistant cells to drug sensitivity. Increasing the EGS-to-target mRNA
      ratio by changing gene copy number or the number of EGSs complementary to
      different target sites enhances the efficiency of the conversion process. We
      demonstrate a general method for the efficient phenotypic conversion of drug
      resistant bacterial cultures.

PMID- 9237999
TI  - MLN64 contains a domain with homology to the steroidogenic acute regulatory
      protein (StAR) that stimulates steroidogenesis.
AB  - MLN64 is a protein that is highly expressed in certain breast carcinomas. The C
      terminus of MLN64 shares significant homology with the steroidogenic acute
      regulatory protein (StAR), which plays a key role in steroid hormone biosynthesis
      by enhancing the intramitochondrial translocation of cholesterol to the
      cholesterol side-chain cleavage enzyme. We tested the ability of MLN64 to
      stimulate steroidogenesis by using COS-1 cells cotransfected with plasmids
      expressing the human cholesterol side-chain cleavage enzyme system and wild-type
      and mutant MLN64 proteins. Wild-type MLN64 increased pregnenolone secretion in
      this system 2-fold. The steroidogenic activity of MLN64 was found to reside in
      the C terminus of the protein, because constructs from which the C-terminal StAR
      homology domain was deleted had no steroidogenic activity. In contrast, removal
      of N-terminal sequences increased MLN64's steroidogenesis-enhancing activity.
      MLN64 mRNA was found in many human tissues, including the placenta and brain,
      which synthesize steroid hormones but do not express StAR. Western blot analysis
      revealed the presence of lower molecular weight immunoreactive MLN64 species that
      contain the C-terminal sequences in human tissues. Homologs of both MLN64 and
      StAR were identified in Caenorhabditis elegans, indicating that the two proteins
      are ancient. Mutations that inactivate StAR were correlated with amino acid
      residues that are identical or similar among StAR and MLN64, indicating that
      conserved motifs are important for steroidogenic activity. We conclude that MLN64
      stimulates steroidogenesis by virtue of its homology to StAR.

PMID- 9238001
TI  - The U5 RNA of trypanosomes deviates from the canonical U5 RNA: the Leptomonas
      collosoma U5 RNA and its coding gene.
AB  - Fractionation of the abundant small ribonucleoproteins (RNPs) of the
      trypanosomatid Leptomonas collosoma revealed the existence of a group of
      unidentified small RNPs that were shown to fractionate differently than the well
      characterized trans-spliceosomal RNPs. One of these RNAs, an 80-nt RNA, did not
      possess a trimethylguanosine (TMG) cap structure but did possess a 5' phosphate
      terminus and an invariant consensus U5 snRNA loop 1. The gene coding for the RNA
      was cloned, and the coding region showed 55% sequence identity to the recently
      described U5 homologue of Trypanosoma brucei [Dungan, J. D., Watkins, K. P. &
      Agabian, N. (1996) EMBO J. 15, 4016-4029]. The L. collosoma U5 homologue exists
      in multiple forms of RNP complexes, a 10S monoparticle, and two subgroups of 18S
      particles that either contain or lack the U4 and U6 small nuclear RNAs,
      suggesting the existence of a U4/U6.U5 tri-small nuclear RNP complex. In contrast
      to T. brucei U5 RNA (62 nt), the L. collosoma homologue is longer (80 nt) and
      possesses a second stem-loop. Like the trypanosome U3, U6, and 7SL RNA genes, a
      tRNA gene coding for tRNACys was found 98 nt upstream to the U5 gene. A potential
      for base pair interaction between U5 and SL RNA in the 5' splice site region
      (positions -1 and +1) and downstream from it is proposed. The presence of a U5
      like RNA in trypanosomes suggests that the most essential small nuclear RNPs are
      ubiquitous for both cis- and trans-splicing, yet even among the trypanosomatids
      the U5 RNA is highly divergent.

PMID- 9238002
TI  - RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1
      and TIF2.
AB  - Steroids, thyroid hormones, vitamin D3, and retinoids are lipophilic small
      molecules that regulate diverse biological effects such as cell differentiation,
      development, and homeostasis. The actions of these hormones are mediated by
      steroid/nuclear receptors which function as ligand-dependent transcriptional
      regulators. Transcriptional activation by ligand-bound receptors is a complex
      process requiring dissociation and recruitment of several additional cofactors.
      We report here the cloning and characterization of receptor-associated
      coactivator 3 (RAC3), a human transcriptional coactivator for steroid/nuclear
      receptors. RAC3 interacts with several liganded receptors through a mechanism
      which requires their respective ligand-dependent activation domains. RAC3 can
      activate transcription when tethered to a heterologous DNA-binding domain.
      Overexpression of RAC3 enhances the ligand-dependent transcriptional activation
      by the receptors in mammalian cells. Sequence analysis reveals that RAC3 is
      related to steroid receptor coactivator 1 (SRC-1) and transcriptional
      intermediate factor 2 (TIF2), two of the most potent coactivators for
      steroid/nuclear receptors. Thus, RAC3 is a member of a growing coactivator
      network that should be useful as a tool for understanding hormone action and as a
      target for developing new therapeutic agents that can block hormone-dependent
      neoplasia.

PMID- 9238003
TI  - Interaction of the human androgen receptor transactivation function with the
      general transcription factor TFIIF.
AB  - The human androgen receptor (AR) is a ligand-activated transcription factor that
      regulates genes important for male sexual differentiation and development. To
      better understand the role of the receptor as a transcription factor we have
      studied the mechanism of action of the N-terminal transactivation function. In a
      protein-protein interaction assay the AR N terminus (amino acids 142-485)
      selectively bound to the basal transcription factors TFIIF and the TATA-box
      binding protein (TBP). Reconstitution of the transactivation activity in vitro
      revealed that AR142-485 fused to the LexA protein DNA-binding domain was
      competent to activate a reporter gene in the presence of a competing DNA template
      lacking LexA binding sites. Furthermore, consistent with direct interaction with
      basal transcription factors, addition of recombinant TFIIF relieved squelching of
      basal transcription by AR142-485. Taken together these results suggest that one
      mechanism of transcriptional activation by the AR involves binding to TFIIF and
      recruitment of the transcriptional machinery.

PMID- 9238004
TI  - A glutamate residue in the catalytic center of the yeast chorismate mutase
      restricts enzyme activity to acidic conditions.
AB  - Chorismate mutase acts at the first branchpoint of aromatic amino acid
      biosynthesis and catalyzes the conversion of chorismate to prephenate. Comparison
      of the x-ray structures of allosteric chorismate mutase from the yeast
      Saccharomyces cerevisiae with Escherichia coli chorismate mutase/prephenate
      dehydratase suggested conserved active sites between both enzymes. We have
      replaced all critical amino acid residues, Arg-16, Arg-157, Lys-168, Glu-198, Thr
      242, and Glu-246, of yeast chorismate mutase by aliphatic amino acid residues.
      The resulting enzymes exhibit the necessity of these residues for catalytic
      function and provide evidence of their localization at the active site. Unlike
      some bacterial enzymes, yeast chorismate mutase has highest activity at acidic pH
      values. Replacement of Glu-246 in the yeast chorismate mutase by glutamine
      changes the pH optimum for activity of the enzyme from a narrow to a broad pH
      range. These data suggest that Glu-246 in the catalytic center must be protonated
      for maximum catalysis and restricts optimal activity of the enzyme to low pH.

PMID- 9238005
TI  - Use of intrinsic binding energy for catalysis by an RNA enzyme.
AB  - The contribution of several individual ribozyme.substrate base pairs to binding
      and catalysis has been investigated using hammerhead ribozyme substrates that
      were truncated at their 3' or 5' ends. The base pairs at positions 1.1-2.1 and
      15.2-16.2, which flank the conserved core, each contribute 10(4)-fold in the
      chemical step, without affecting substrate binding. In contrast, base pairs
      distal to the core contribute to substrate binding but have no effect on the
      chemical step. These results suggest a "fraying model" in which each
      ribozyme.substrate helix can exist in either an unpaired ("open") state or a
      helical ("closed") state, with the closed state required for catalysis. The base
      pairs directly adjacent to the conserved core contribute to catalysis by allowing
      the closed state to form. Once the number of base pairs is sufficient to ensure
      that the closed helical state predominates, additional residues provide
      stabilization of the helix, and therefore increase binding, but have no further
      effect on the chemical step. Remarkably, the >5 kcal/mol free energy contribution
      to catalysis from each of the internal base pairs is considerably greater than
      the free energy expected for formation of a base pair. It is suggested that this
      unusually large energetic contribution arises because free energy that is
      typically lost in constraining residues within a base pair is expressed in the
      transition state, where it is used for positioning. This extends the concept of
      "intrinsic binding energy" from protein to RNA enzymes, suggesting that intrinsic
      binding energy is a fundamental feature of biological catalysis.

PMID- 9238006
TI  - Identification by mass spectrometry of the phosphorylated residue responsible for
      activation of the catalytic domain of myosin I heavy chain kinase, a member of
      the PAK/STE20 family.
AB  - Myosin I heavy chain kinase from Acanthamoeba castellanii is activated in vitro
      by autophosphorylation (8-10 mol of P per mol). The catalytically active C
      terminal domain produced by trypsin cleavage of the phosphorylated kinase
      contains 2-3 mol of P per mol. However, the catalytic domain expressed in a
      baculovirus-insect cell system is fully active as isolated without
      autophosphorylation in vitro. We now show that the expressed catalytic domain is
      inactivated by incubation with acid phosphatase and regains activity upon
      autophosphorylation. The state of phosphorylation of all of the hydroxyamino
      acids in the catalytic domain were determined by mass spectrometry of
      unfractionated protease digests. Ser-627 was phosphorylated in the active,
      expressed catalytic domain, lost its phosphate when the protein was incubated
      with phosphatase, and was rephosphorylated when the dephosphorylated protein was
      incubated with ATP. No other residue was significantly phosphorylated in any of
      the three samples. Thus, phosphorylation of Ser-627, which is in the same
      position as the Ser and Thr residues that are phosphorylated in many other
      kinases, is necessary and sufficient for full activity of the catalytic domain.
      Ser-627 is also phosphorylated when full-length, native kinase is activated by
      autophosphorylation.

PMID- 9238007
TI  - Molecular cloning of a peroxisomal Ca2+-dependent member of the mitochondrial
      carrier superfamily.
AB  - A cDNA from a novel Ca2+-dependent member of the mitochondrial solute carrier
      superfamily was isolated from a rabbit small intestinal cDNA library. The full
      length cDNA clone was 3,298 nt long and coded for a protein of 475 amino acids,
      with four elongation factor-hand motifs located in the N-terminal half of the
      molecule. The 25-kDa N-terminal polypeptide was expressed in Escherichia coli,
      and it was demonstrated that it bound Ca2+, undergoing a reversible and specific
      conformational change as a result. The conformation of the polypeptide was
      sensitive to Ca2+ which was bound with high affinity (Kd approximately 0.37
      microM), the apparent Hill coefficient for Ca2+-induced changes being about 2.0.
      The deduced amino acid sequence of the C-terminal half of the molecule revealed
      78% homology to Grave disease carrier protein and 67% homology to human ADP/ATP
      translocase; this sequence homology identified the protein as a new member of the
      mitochondrial transporter superfamily. Northern blot analysis revealed the
      presence of a single transcript of about 3,500 bases, and low expression of the
      transporter could be detected in the kidney but none in the liver. The main site
      of expression was the colon with smaller amounts found in the small intestine
      proximal to the ileum. Immunoelectron microscopy localized the transporter in the
      peroxisome, although a minor fraction was found in the mitochondria. The Ca2+
      binding N-terminal half of the transporter faces the cytosol.

PMID- 9238008
TI  - AtGRP7, a nuclear RNA-binding protein as a component of a circadian-regulated
      negative feedback loop in Arabidopsis thaliana.
AB  - The endogenous clock that drives circadian rhythms is thought to communicate
      temporal information within the cell via cycling downstream transcripts. A
      transcript encoding a glycine-rich RNA-binding protein, Atgrp7, in Arabidopsis
      thaliana undergoes circadian oscillations with peak levels in the evening. The
      AtGRP7 protein also cycles with a time delay so that Atgrp7 transcript levels
      decline when the AtGRP7 protein accumulates to high levels. After AtGRP7 protein
      concentration has fallen to trough levels, Atgrp7 transcript starts to
      reaccumulate. Overexpression of AtGRP7 in transgenic Arabidopsis plants severely
      depresses cycling of the endogenous Atgrp7 transcript. These data establish both
      transcript and protein as components of a negative feedback circuit capable of
      generating a stable oscillation. AtGRP7 overexpression also depresses the
      oscillation of the circadian-regulated transcript encoding the related RNA
      binding protein AtGRP8 but does not affect the oscillation of transcripts such as
      cab or catalase mRNAs. We propose that the AtGRP7 autoregulatory loop represents
      a "slave" oscillator in Arabidopsis that receives temporal information from a
      central "master" oscillator, conserves the rhythmicity by negative feedback, and
      transduces it to the output pathway by regulating a subset of clock-controlled
      transcripts.

PMID- 9238009
TI  - In vitro selection of a 7-methyl-guanosine binding RNA that inhibits translation
      of capped mRNA molecules.
AB  - Using systematic evolution of ligands by exponential enrichment (SELEX), an RNA
      molecule was isolated that displays a 1,000-fold higher affinity for guanosine
      residues that carry an N-7 methyl group than for nonmethylated guanosine
      residues. The methylated guanosine residue closely resembles the 5' terminal cap
      structure present on all eukaryotic mRNA molecules. The cap-binding RNA
      specifically inhibited the translation of capped but not uncapped mRNA molecules
      in cell-free lysates prepared from either human HeLa cells or from Saccharomyces
      cerevisiae. These findings indicate that the cap-binding RNA will also be useful
      in studies of other cap-dependent processes such as pre-mRNA splicing and
      nucleocytoplasmic mRNA transport.

PMID- 9238010
TI  - The product of a thyroid hormone-responsive gene interacts with thyroid hormone
      receptors.
AB  - Thyroid hormone is a critical mediator of central nervous system (CNS)
      development, acting through nuclear receptors to modulate the expression of
      specific genes. Transcription of the rat hairless (hr) gene is highly up
      regulated by thyroid hormone in the developing CNS; we show here that hr is
      directly induced by thyroid hormone. By identifying proteins that interact with
      the hr gene product (Hr), we find that Hr interacts directly and specifically
      with thyroid hormone receptor (TR)-the same protein that regulates its
      expression. Unlike previously described receptor-interacting factors, Hr
      associates with TR and not with retinoic acid receptors (RAR, RXR). Hr can act as
      a transcriptional repressor, suggesting that its interaction with TR is part of a
      novel autoregulatory mechanism.

PMID- 9238012
TI  - The load dependence of kinesin's mechanical cycle.
AB  - Kinesin is a dimeric motor protein that transports organelles in a stepwise
      manner toward the plus-end of microtubules by converting the energy of ATP
      hydrolysis into mechanical work. External forces can influence the behavior of
      kinesin, and force-velocity curves have shown that the motor will slow down and
      eventually stall under opposing loads of approximately 5 pN. Using an in vitro
      motility assay in conjunction with a high-resolution optical trapping microscope,
      we have examined the behavior of individual kinesin molecules under two
      previously unexplored loading regimes: super-stall loads (>5 pN) and forward
      (plus-end directed) loads. Whereas some theories of kinesin function predict a
      reversal of directionality under high loads, we found that kinesin does not walk
      backwards under loads of up to 13 pN, probably because of an irreversible
      transition in the mechanical cycle. We also found that this cycle can be
      significantly accelerated by forward loads under a wide range of ATP
      concentrations. Finally, we noted an increase in kinesin's rate of dissociation
      from the microtubule with increasing load, which is consistent with a load
      dependent partitioning between two recently described kinetic pathways: a
      coordinated-head pathway (which leads to stepping) and an independent-head
      pathway (which is static).

PMID- 9238011
TI  - The structure of the acto-myosin subfragment 1 complex: results of searches using
      data from electron microscopy and x-ray crystallography.
AB  - Surmises of how myosin subfragment 1 (S1) interacts with actin filaments in
      muscle contraction rest upon knowing the relative arrangement of the two
      proteins. Although there exist crystallographic structures for both S1 and actin,
      as well as electron microscopy data for the acto-S1 complex (AS1), modeling of
      this arrangement has so far only been done "by eye." Here we report fitted AS1
      structures obtained using a quantitative method that is both more objective and
      makes more complete use of the data. Using undistorted crystallographic results,
      the best-fit AS1 structure shows significant differences from that obtained by
      visual fitting. The best fit is produced using the F-actin model of Holmes et al.
      [Holmes, K. C., Popp, D., Gebhard, W. & Kabsch, W. (1990) Nature (London) 347, 44
      49]. S1 residues at the AS1 interface are now found at a higher radius as well as
      being translated axially and rotated azimuthally. Fits using S1 plus loops
      missing from the crystal structure were achieved using a homology search method
      to predict loop structures. These improved fits favor an arrangement in which the
      loop at the 50- to 20-kDa domain junction of S1 is located near the N terminus of
      actin. Rigid-body movements of the lower 50-kDa domain, which further improve the
      fit, produce closure of the large 50-kDa domain cleft and bring conserved
      residues in the lower 50-kDa domain into an apparently appropriate orientation
      for close interaction with actin. This finding supports the idea that binding of
      ATP to AS1 at the end of the ATPase cycle disrupts the actin binding site by
      changing the conformation of the 50-kDa cleft of S1.

PMID- 9238014
TI  - Complete resolution of the solid-state NMR spectrum of a uniformly 15N-labeled
      membrane protein in phospholipid bilayers.
AB  - Complete resolution of the amide resonances in a three-dimensional solid-state
      NMR correlation spectrum of a uniformly 15N-labeled membrane protein in oriented
      phospholipid bilayers is demonstrated. The three orientationally dependent
      frequencies, 1H chemical shift, 1H-15N dipolar coupling, and 15N chemical shift,
      associated with each amide resonance are responsible for resolution among
      resonances and provide sufficient angular restrictions for protein structure
      determination. Because the protein is completely immobilized by the phospholipids
      on the relevant NMR time scales (10 kHz), the linewidths will not degrade in the
      spectra of larger proteins. Therefore, these results demonstrate that solid-state
      NMR experiments can overcome the correlation time problem and extend the range of
      proteins that can have their structures determined by NMR spectroscopy to include
      uniformly 15N-labeled membrane proteins in phospholipid bilayers.

PMID- 9238013
TI  - Ultrafast signals in protein folding and the polypeptide contracted state.
AB  - To test the significance of ultrafast protein folding signals (<<1 msec), we
      studied cytochrome c (Cyt c) and two Cyt c fragments with major C-terminal
      segments deleted. The fragments remain unfolded under all conditions and so could
      be used to define the unfolded baselines for protein fluorescence and circular
      dichroism (CD) as a function of denaturant concentration. When diluted from high
      to low denaturant in kinetic folding experiments, the fragments readjust to their
      new baseline values in a "burst phase" within the mixing dead time. The fragment
      burst phase reflects a contraction of the polypeptide from a more extended
      unfolded condition at high denaturant to a more contracted unfolded condition in
      the poorer, low denaturant solvent. Holo Cyt c exhibits fluorescence and CD burst
      phase signals that are essentially identical to the fragment signals over the
      whole range of final denaturant concentrations, evidently reflecting the same
      solvent-dependent, relatively nonspecific contraction and not the formation of a
      specific folding intermediate. The significance of fast folding signals in Cyt c
      and other proteins is discussed in relation to the hypothesis of an initial rate
      limiting search-nucleation-collapse step in protein folding [Sosnick, T. R.,
      Mayne, L. & Englander, S. W. (1996) Proteins Struct. Funct. Genet. 24, 413-426].

PMID- 9238015
TI  - Chromophore structural changes in rhodopsin from nanoseconds to microseconds
      following pigment photolysis.
AB  - Rhodopsin is a prototypical G protein-coupled receptor that is activated by
      photoisomerization of its 11-cis-retinal chromophore. Mutant forms of rhodopsin
      were prepared in which the carboxylic acid counterion was moved relative to the
      positively charged chromophore Schiff base. Nanosecond time-resolved laser
      photolysis measurements of wild-type recombinant rhodopsin and two mutant
      pigments then were used to determine reaction schemes and spectra of their early
      photolysis intermediates. These results, together with linear dichroism data,
      yielded detailed structural information concerning chromophore movements during
      the first microsecond after photolysis. These chromophore structural changes
      provide a basis for understanding the relative movement of rhodopsin's
      transmembrane helices 3 and 6 required for activation of rhodopsin. Thus, early
      structural changes following isomerization of retinal are linked to the
      activation of this G protein-coupled receptor. Such rapid structural changes lie
      at the heart of the pharmacologically important signal transduction mechanisms in
      a large variety of receptors, which use extrinsic activators, but are impossible
      to study in receptors using diffusible agonist ligands.

PMID- 9238016
TI  - Receptor-associated constitutive protein tyrosine phosphatase activity controls
      the kinase function of JAK1.
AB  - Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an
      increase in the phosphotyrosine content of many cellular proteins. However, the
      level at which the primary signaling event is affected is still unclear. We show
      that Jaks are activated by tyrosine phosphorylation in cells that are briefly
      exposed to the PTP inhibitor pervanadate (PV), resulting in tyrosine
      phosphorylation and functional activation of Stat6 (in addition to other Stats).
      Mutant cell lines that lack Jak1 activity fail to support PV-mediated [or
      interleukin 4 (IL-4)-dependent] activation of Stat6 but can be rescued by
      complementation with functional Jak1. The docking sites for both Jak1 and Stat6
      reside in the cytoplasmic domain of the IL-4 receptor alpha-chain (IL-4Ralpha).
      The glioblastoma-derived cell lines T98G, GRE, and M007, which do not express the
      IL-4Ralpha chain, fail to support Stat6 activation in response to either IL-4 or
      PV. Complementation of T98G cells with the IL-4Ralpha restores both PV-mediated
      and IL-4-dependent Stat6 activation. Murine L929 cells, which do not express the
      gamma common chain of the IL-4 receptor, support PV-mediated but not IL-4
      dependent Stat6 activation. Thus, Stat6 activation by PV is an IL-4Ralpha
      mediated, Jak1-dependent event that is independent of receptor dimerization. We
      propose that receptor-associated constitutive PTP activity functions to down
      regulate persistent, receptor-linked kinase activity. Inhibition or deletion of
      PTP activity results in constitutive activation of cytokine signaling pathways.

PMID- 9238017
TI  - The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin and
      dynamin via a Grb2-like Src homology 3 domain.
AB  - The GTPase dynamin I and the inositol 5-phosphatase synaptojanin are nerve
      terminal proteins implicated in synaptic vesicle recycling. Both proteins contain
      COOH-terminal proline-rich domains that can interact with a variety of Src
      homology 3 (SH3) domains. A major physiological binding partner for dynamin I and
      synaptojanin in the nervous system is amphiphysin I, an SH3 domain-containing
      protein also concentrated in nerve terminals. We have used the proline-rich tail
      of synaptojanin to screen a rat brain library by the two-hybrid method to
      identify additional interacting partners of synaptojanin. Three related proteins
      containing SH3 domains that are closely related to the SH3 domains of Grb2 were
      isolated: SH3p4, SH3p8, and SH3p13. Further biochemical studies demonstrated that
      the SH3p4/8/13 proteins bind to both synaptojanin and dynamin I. The SH3p4/8/13
      transcripts are differentially expressed in tissues: SH3p4 mRNA was detected only
      in brain, SH3p13 mRNA was present in brain and testis, and the SH3p8 transcript
      was detected at similar levels in multiple tissues. Members of the SH3p4/8/13
      protein family were found to be concentrated in nerve terminals, and pools of
      synaptojanin and dynamin I were coprecipitated from brain extracts with
      antibodies recognizing SH3p4/8/13. These findings underscore the important role
      of SH3-mediated interactions in synaptic vesicle recycling.

PMID- 9238018
TI  - A novel role for clathrin in cytokinesis.
AB  - Using clathrin-minus Dictyostelium cells, we identified a novel requirement for
      clathrin during cytokinesis. In suspension culture, clathrin-minus cells failed
      to divide and became large and multinucleate. This cytokinesis deficiency was not
      attributable to a pleiotropic effect on the actomyosin cytoskeleton, since other
      cellular events driven by myosin II (e.g., cortical contraction and capping of
      concanavalin A receptors) remained intact in clathrin-minus cells. Examination of
      cells expressing myosin II tagged with green fluorescent protein showed that
      clathrin-minus cells failed to assemble myosin II into a functional contractile
      ring. This inability to localize myosin II to a particular location was specific
      for cytokinesis, since clathrin-minus cells moving across a substrate localized
      myosin II properly to their posterior cortexes. These results demonstrate that
      clathrin is essential for construction of a functional contractile ring during
      cell division.

PMID- 9238019
TI  - ECA1 complements yeast mutants defective in Ca2+ pumps and encodes an endoplasmic
      reticulum-type Ca2+-ATPase in Arabidopsis thaliana.
AB  - To understand the structure, role, and regulation of individual Ca2+ pumps in
      plants, we have used yeast as a heterologous expression system to test the
      function of a gene from Arabidopsis thaliana (ECA1). ECA1 encoded a 116-kDa
      polypeptide that has all the conserved domains common to P-type Ca2+ pumps (EC
      3.6.1.38). The amino acid sequence shared more identity with
      sarcoplasmic/endoplasmic reticulum (53%) than with plasma membrane (32%) Ca2+
      pumps. Yeast mutants defective in a Golgi Ca2+ pump (pmr1) or both Golgi and
      vacuolar Ca2+ pumps (pmr1 pmc1 cnb1) were sensitive to growth on medium
      containing 10 mM EGTA or 3 mM Mn2+. Expression of ECA1 restored growth of either
      mutant on EGTA. Membranes were isolated from the pmr1 pmc1 cnb1 mutant
      transformed with ECA1 to determine if the ECA1 polypeptide (ECA1p) could be
      phosphorylated as intermediates of the reaction cycle of Ca2+-pumping ATPases. In
      the presence of [gamma-32P]ATP, ECA1p formed a Ca2+-dependent [32P]phosphoprotein
      of 106 kDa that was sensitive to hydroxylamine. Cyclopiazonic acid, a blocker of
      animal sarcoplasmic/endoplasmic reticulum Ca2+ pumps, inhibited the formation of
      the phosphoprotein, whereas thapsigargin did not. Immunoblotting with an antibody
      against the carboxyl tail showed that ECA1p was associated mainly with the
      endoplasmic reticulum membranes isolated from Arabidopsis plants. The results
      support the model that ECA1 encodes an endoplasmic reticulum-type Ca2+ pump in
      Arabidopsis. The ability of ECA1p to restore growth of mutant pmr1 on medium
      containing Mn2+, and the formation of a Mn2+-dependent phosphoprotein suggested
      that ECA1p may also regulate Mn2+ homeostasis by pumping Mn2+ into endomembrane
      compartments of plants.

PMID- 9238020
TI  - Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3.
AB  - Salt and water secretion from intestinal epithelia requires enhancement of anion
      permeability across the apical membrane of Cl- secreting cells lining the crypt,
      the secretory gland of the intestine. Paneth cells located at the base of the
      small intestinal crypt release enteric defensins (cryptdins) apically into the
      lumen. Because cryptdins are homologs of molecules known to form anion conductive
      pores in phospholipid bilayers, we tested whether these endogenous antimicrobial
      peptides could act as soluble inducers of channel-like activity when applied to
      apical membranes of intestinal Cl- secreting epithelial cells in culture. Of the
      six peptides tested, cryptdins 2 and 3 stimulated Cl- secretion from polarized
      monolayers of human intestinal T84 cells. The response was reversible and dose
      dependent. In contrast, cryptdins 1, 4, 5, and 6 lacked this activity,
      demonstrating that Paneth cell defensins with very similar primary structures may
      exhibit a high degree of specificity in their capacity to elicit Cl- secretion.
      The secretory response was not inhibited by pretreatment with 8-phenyltheophyline
      (1 microM), or dependent on a concomitant rise in intracellular cAMP or cGMP,
      indicating that the apically located adenosine and guanylin receptors were not
      involved. On the other hand, cryptdin 3 elicited a secretory response that
      correlated with the establishment of an apically located anion conductive channel
      permeable to carboxyfluorescein. Thus cryptdins 2 and 3 can selectively
      permeabilize the apical cell membrane of epithelial cells in culture to elicit a
      physiologic Cl- secretory response. These data define the capability of cryptdins
      2 and 3 to function as novel intestinal secretagogues, and suggest a previously
      undescribed mechanism of paracrine signaling that in vivo may involve the
      reversible formation of ion conductive channels by peptides released into the
      crypt microenvironment.

PMID- 9238021
TI  - Importin/karyopherin protein family members required for mRNA export from the
      nucleus.
AB  - The yeast Saccharomyces cerevisiae contains three proteins (Kap104p, Pse1p, and
      Kap123p) that share similarity to the 95-kDa beta subunit of the nuclear
      transport factor importin (also termed karyopherin and encoded by KAP95/RSL1 in
      yeast). Proteins that contain nuclear localization sequences are recognized in
      the cytoplasm and delivered to the nucleus by the heterodimeric importin complex.
      A second importin-related protein, transportin, delivers a subset of
      heterogeneous nuclear ribonucleoproteins (hnRNPs) to the nucleoplasm. We now show
      that in contrast to loss of importin beta (Kap95p/Rsl1p) and transportin
      (Kap104p), conditional loss of Pse1p in a strain lacking Kap123p results in a
      specific block of mRNA export from the nucleus. Overexpression of Sxm1p, a
      protein related to Cse1p in yeast and to the human cellular apoptosis
      susceptibility protein, relieves the defects of cells lacking Pse1p and Kap123p.
      Thus, a major role of Pse1p, Kap123p, and Sxm1p may be nuclear export rather than
      import, suggesting a symmetrical relationship between these processes.

PMID- 9238022
TI  - Anteroposterior neural tissue specification by activin-induced mesoderm.
AB  - The transforming growth factor beta superfamily member, activin, is able to
      induce mesodermal tissues in animal cap explants from Xenopus laevis blastula
      stage embryos. Activin can act like a morphogen of the dorsoventral axis in that
      lower doses induce more ventral, and higher doses more dorsal, tissue types.
      Activin has also previously been reported to induce neural tissues in animal
      caps. From cell mixing experiments it was inferred that this might be an indirect
      effect of induced mesoderm signaling to uninduced ectoderm. Here we demonstrate
      directly that neural tissues do indeed arise by the action of induced mesoderm on
      uninduced ectoderm. Dorsal mesoderm is itself subdivided into posterior and
      anterior domains in vivo, but this had not been demonstrated for induced
      mesoderm. We therefore tested whether different concentrations of activin
      recreate these different anteroposterior properties as well. We show that the
      anteroposterior positional value of induced mesoderm, including its
      neuroinductive properties, depends on the dose of activin applied to the
      mesoderm, with lower doses inducing more posterior and higher doses giving more
      anterior markers. We discuss the implications of these results for patterning
      signals and the relationship between anteroposterior and dorsoventral axes.

PMID- 9238023
TI  - Relax promotes ectopic neuronal differentiation in Xenopus embryos.
AB  - We previously isolated a novel rat cDNA encoding a basic helix-loop-helix
      transcription factor named Relax, whose expression in the developing central
      nervous system is strictly limited to discrete domains containing precursor
      cells. The timing of Relax expression coincides with neuronal differentiation. To
      investigate the involvement of Relax in neurogenesis we tested whether Relax
      activated neural genes in the ectoderm by injecting Relax RNA into Xenopus
      embryos. We demonstrate that ectopic Relax expression induces a persistent
      enlargement of the neural plate and converts presumptive epidermal cells into
      neurons. This indicates that Relax, when overexpressed in Xenopus embryos, has a
      neuronal fate-determination function. Analyses both of Relax overexpression in
      the frog and of the distribution of Relax in the rat neural tube strongly suggest
      that Relax is a neuronal fate-determination gene.

PMID- 9238024
TI  - Epidermal muscle attachment site-specific target gene expression and interference
      with myotube guidance in response to ectopic stripe expression in the developing
      Drosophila epidermis.
AB  - The egr-type zinc-finger transcription factor encoded by the Drosophila gene
      stripe (sr) is expressed in a subset of epidermal cells to which muscles attach
      during late stages of embryogenesis. We report loss-of-function and gain-of
      function experiments indicating that sr activity provides ectodermal cells with
      properties required for the establishment of a normal muscle pattern during
      embryogenesis and for the differentiation of tendon-like epidermal muscle
      attachment sites (EMA). Our results show that sr encodes a transcriptional
      activator which acts as an autoregulated developmental switch gene. sr activity
      controls the expression of EMA-specific target genes in cells of ectodermal but
      not of mesodermal origin. sr-expressing ectodermal cells generate long-range
      signals that interfere with the spatial orientation of the elongating myotubes.

PMID- 9238026
TI  - Ultraviolet plumage colors predict mate preferences in starlings.
AB  - Avian plumage has long been used to test theories of sexual selection, with
      humans assessing the colors. However, many birds see in the ultraviolet (<400
      nm), to which humans are blind. Consequently, it is important to know whether
      natural variation in UV reflectance from plumage functions in sexual signaling.
      We show that female starlings rank males differently when UV wavelengths are
      present or absent. Principal component analysis of approximately 1300 reflectance
      spectra (300-700 nm) taken from sexually dimorphic plumage regions of males
      predicted preference under the UV+ treatment. Under UV- conditions, females
      ranked males in a different and nonrandom order, but plumage reflectance in the
      human visible spectrum did not predict choice. Natural variation in UV
      reflectance is thus important in avian mate assessment, and the prevailing light
      environment can have profound effects on observed mating preferences.

PMID- 9238025
TI  - A peptide export-import control circuit modulating bacterial development
      regulates protein phosphatases of the phosphorelay.
AB  - The phosphorelay signal transduction system activates developmental transcription
      in sporulation of Bacillus subtilis by phosphorylation of aspartyl residues of
      the Spo0F and Spo0A response regulators. The phosphorylation level of these
      response regulators is determined by the opposing activities of protein kinases
      and protein aspartate phosphatases that interpret positive and negative signals
      for development in a signal integration circuit. The RapA protein aspartate
      phosphatase of the phosphorelay is regulated by a peptide that directly inhibits
      its activity. This peptide is proteolytically processed from an inactive pre
      inhibitor protein encoded in the phrA gene. The pre-inhibitor is cleaved by the
      protein export apparatus to a putative pro-inhibitor that is further processed to
      the active inhibitor peptide and internalized by the oligopeptide permease. This
      export-import circuit is postulated to be a mechanism for timing phosphatase
      activity where the processing enzymes regulate the rate of formation of the
      active inhibitor. The processing events may, in turn, be controlled by a
      regulatory hierarchy. Chromosome sequencing has revealed several other
      phosphatase-prepeptide gene pairs in B. subtilis, suggesting that the use of this
      mechanism may be widespread in signal transduction.

PMID- 9238027
TI  - Both apolipoprotein E and A-I genes are present in a nonmammalian vertebrate and
      are highly expressed during embryonic development.
AB  - Apolipoprotein E (apoE) is associated with several classes of plasma lipoproteins
      and mediates uptake of lipoproteins through its ability to interact with specific
      cell surface receptors. Besides its role in cardiovascular diseases, accumulating
      evidence has suggested that apoE could play a role in neurodegenerative diseases,
      such as Alzheimer disease. In vertebrates, apoA-I is the major protein of high
      density lipoprotein. ApoA-I may play an important role in regulating the
      cholesterol content of peripheral tissues through the reverse cholesterol
      transport pathway. We have isolated cDNA clones that code for apoE and apoA-I
      from a zebrafish embryo library. Analysis of the deduced amino acid sequences
      showed the presence of a region enriched in basic amino acids in zebrafish apoE
      similar to the lipoprotein receptor-binding region of human apoE. We demonstrated
      by whole-mount in situ hybridization that apoE and apoA-I genes are highly
      expressed in the yolk syncytial layer, an extraembryonic structure implicated in
      embryonic and larval nutrition. ApoE transcripts were also observed in the deep
      cell layer during blastula stage, in numerous ectodermal derivatives after
      gastrulation, and after 3 days of development in a limited number of cells both
      in brain and in the eyes. Our data indicate that apoE can be found in a
      nonmammalian vertebrate and that the duplication events, from which apoE and apoA
      I genes arose, occurred before the divergence of the tetrapod and teleost
      ancestors. Zebrafish can be used as a simple and useful model for studying the
      role of apolipoproteins in embryonic and larval nutrition and of apoE in brain
      morphogenesis and regeneration.

PMID- 9238028
TI  - What initiates speciation in passion-vine butterflies?
AB  - Studies of the continuum between geographic races and species provide the
      clearest insights into the causes of speciation. Here we report on mate choice
      and hybrid viability experiments in a pair of warningly colored butterflies,
      Heliconius erato and Heliconius himera, that maintain their genetic integrity in
      the face of hybridization. Hybrid sterility and inviability have been unimportant
      in the early stages of speciation of these two Heliconius. We find no evidence of
      reduced fecundity, egg hatch, or larval survival nor increases in developmental
      time in three generations of hybrid crosses. Instead, speciation in this pair
      appears to have been catalyzed by the association of strong mating preferences
      with divergence in warning coloration and ecology. In mate choice experiments,
      matings between the two species are a tenth as likely as matings within species.
      F1 hybrids of both sexes mate frequently with both pure forms. However, male F1
      progeny from crosses between H. himera mothers and H. erato fathers have somewhat
      reduced mating success. The strong barrier to gene flow provided by divergence in
      mate preference is probably enhanced by frequency-dependent predation against
      hybrids similar to the type known to occur across interracial hybrid zones of H.
      erato. In addition, the transition between this pair falls at the boundary
      between wet and dry forest, and rare hybrids may also be selected against because
      they are poorly adapted to either biotope. These results add to a growing body of
      evidence that challenge the importance of genomic incompatibilities in the
      earliest stages of speciation.

PMID- 9238029
TI  - Rapid evolution of sex-related genes in Chlamydomonas.
AB  - Biological speciation ultimately results in prezygotic isolation-the inability of
      incipient species to mate with one another-but little is understood about the
      selection pressures and genetic changes that generate this outcome. The genus
      Chlamydomonas comprises numerous species of unicellular green algae, including
      numerous geographic isolates of the species C. reinhardtii. This diverse
      collection has allowed us to analyze the evolution of two sex-related genes: the
      mid gene of C. reinhardtii, which determines whether a gamete is mating-type plus
      or minus, and the fus1 gene, which dictates a cell surface glycoprotein utilized
      by C. reinhardtii plus gametes to recognize minus gametes. Low stringency
      Southern analyses failed to detect any fus1 homologs in other Chlamydomonas
      species and detected only one mid homolog, documenting that both genes have
      diverged extensively during the evolution of the lineage. The one mid homolog was
      found in C. incerta, the species in culture that is most closely related to C.
      reinhardtii. Its mid gene carries numerous nonsynonymous and synonymous codon
      changes compared with the C. reinhardtii mid gene. In contrast, very high
      sequence conservation of both the mid and fus1 sequences is found in natural
      isolates of C. reinhardtii, indicating that the genes are not free to drift
      within a species but do diverge dramatically between species. Striking divergence
      of sex determination and mate recognition genes also has been encountered in a
      number of other eukaryotic phyla, suggesting that unique, and as yet
      unidentified, selection pressures act on these classes of genes during the
      speciation process.

PMID- 9238030
TI  - Pseudotyping of murine leukemia virus with the envelope glycoproteins of HIV
      generates a retroviral vector with specificity of infection for CD4-expressing
      cells.
AB  - CD4-expressing T cells in lymphoid organs are infected by the primary strains of
      HIV and represent one of the main sources of virus replication. Gene therapy
      strategies are being developed that allow the transfer of exogenous genes into
      CD4(+) T lymphocytes whose expression might prevent viral infection or
      replication. Insights into the mechanisms that govern virus entry into the target
      cells can be exploited for this purpose. Major determinants of the tropism of
      infection are the CD4 molecules on the surface of the target cells and the viral
      envelope glycoproteins at the viral surface. The best characterized and most
      widely used gene transfer vectors are derived from Moloney murine leukemia virus
      (MuLV). To generate MuLV-based retroviral gene transfer vector particles with
      specificity of infection for CD4-expressing cells, we attempted to produce viral
      pseudotypes, consisting of MuLV capsid particles and the surface (SU) and
      transmembrane (TM) envelope glycoproteins gp120-SU and gp41-TM of HIV type 1 (HIV
      1). Full-length HIV-1 envelope glycoproteins were expressed in the MuLV env
      negative packaging cell line TELCeB6. Formation of infectious pseudotype
      particles was not observed. However, using a truncated variant of the
      transmembrane protein, lacking sequences of the carboxyl-terminal cytoplasmic
      domain, pseudotyped retroviruses were generated. Removal of the carboxyl-terminal
      domain of the transmembrane envelope protein of HIV-1 was therefore absolutely
      required for the generation of the viral pseudotypes. The virus was shown to
      infect CD4-expressing cell lines, and infection was prevented by antisera
      specific for gp120-SU. This retroviral vector should prove useful for the study
      of HIV infection events mediated by HIV-1 envelope glycoproteins, and for the
      targeting of CD4(+) cells during gene therapy of AIDS.

PMID- 9238031
TI  - Proviral insertions induce the expression of bone-specific isoforms of
      PEBP2alphaA (CBFA1): evidence for a new myc collaborating oncogene.
AB  - The til-1 locus was identified as a common retroviral integration site in virus
      accelerated lymphomas of CD2-myc transgenic mice. We now show that viral
      insertions at til-1 lead to transcriptional activation of PEBP2alphaA (CBFA1), a
      transcription factor related to the Drosophila segmentation gene product, Runt.
      Insertions are upstream and in the opposite orientation to the gene and appear to
      activate a variant promoter that is normally silent in T cells. Activity of this
      promoter was detected in rodent osteogenic sarcoma cells and primary osteoblasts,
      implicating bone as the normal site of promoter activity. The isoforms encoded by
      the activated gene all encompass the conserved runt DNA-binding domain and share
      a novel N terminus different from the previously reported PEBP2alphaA products.
      Minor products include isoforms with internal deletions due to exon skipping and
      a novel C-terminal domain unrelated to known runt domain factors. The major
      isoform expressed from the activated til-1 locus (G1) was found to account for
      virtually all of the core binding factor activity in nuclear extracts from its
      corresponding lymphoma cell line. Another member of this gene family,
      AML1(CBFA2), is well known for its involvement in human hemopoietic tumors. These
      results provide evidence of a direct oncogenic role for PEBP2alphaA and indicate
      that the Myc and Runt family genes can cooperate in oncogenesis.

PMID- 9238032
TI  - Mutagenicity in Escherichia coli of the major DNA adduct derived from the
      endogenous mutagen malondialdehyde.
AB  - The spectrum of mutations induced by the naturally occurring DNA adduct
      pyrimido[1,2-alpha]purin-10(3H)-one (M1G) was determined by site-specific
      approaches using M13 vectors replicated in Escherichia coli. M1G was placed at
      position 6256 in the (-)-strand of M13MB102 by ligating the oligodeoxynucleotide
      5'-GGT(M1G)TCCG-3' into a gapped-duplex derivative of the vector. Unmodified and
      M1G-modified genomes containing either a cytosine or thymine at position 6256 of
      the (+)-strand were transformed into repair-proficient and repair-deficient E.
      coli strains, and base pair substitutions were quantitated by hybridization
      analysis. Modified genomes containing a cytosine opposite M1G resulted in roughly
      equal numbers of M1G-->A and M1G-->T mutations with few M1G-->C mutations. The
      total mutation frequency was approximately 1%, which represents a 500-fold
      increase in mutations compared with unmodified M13MB102. Transformation of
      modified genomes containing a thymine opposite M1G allowed an estimate to be made
      of the ability of M1G to block replication. The (-)-strand was replicated >80% of
      the time in the unadducted genome but only 20% of the time when M1G was present.
      Correction of the mutation frequency for the strand bias of replication indicated
      that the actual frequency of mutations induced by M1G was 18%. Experiments using
      E. coli with different genetic backgrounds indicated that the SOS response
      enhances the mutagenicity of M1G and that M1G is a substrate for repair by the
      nucleotide excision repair complex. These studies indicate that M1G, which is
      present endogenously in DNA of healthy human beings, is a strong block to
      replication and an efficient premutagenic lesion.

PMID- 9238033
TI  - Xeroderma pigmentosum and trichothiodystrophy are associated with different
      mutations in the XPD (ERCC2) repair/transcription gene.
AB  - The xeroderma pigmentosum group D (XPD) protein has a dual function, both in
      nucleotide excision repair of DNA damage and in basal transcription. Mutations in
      the XPD gene can result in three distinct clinical phenotypes, XP,
      trichothiodystrophy (TTD), and XP with Cockayne syndrome. To determine if the
      clinical phenotypes of XP and TTD can be attributed to the sites of the
      mutations, we have identified the mutations in a large group of TTD and XP-D
      patients. Most sites of mutations differed between XP and TTD, but there are
      three sites at which the same mutation is found in XP and TTD patients. Since the
      corresponding patients were all compound heterozygotes with different mutations
      in the two alleles, the alleles were tested separately in a yeast complementation
      assay. The mutations which are found in both XP and TTD patients behaved as null
      alleles, suggesting that the disease phenotype was determined by the other
      allele. If we eliminate the null mutations, the remaining mutagenic pattern is
      consistent with the site of the mutation determining the phenotype.

PMID- 9238035
TI  - Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the
      Idd5 diabetes susceptibility region.
AB  - Defects in lymphocyte apoptosis may lead to autoimmune disorders and contribute
      to the pathogenesis of type 1 diabetes. Lymphocytes of nonobese diabetic (NOD)
      mice, an animal model of autoimmune diabetes, have been found resistant to
      various apoptosis signals, including the alkylating drug cyclophosphamide. Using
      an F2 intercross between the apoptosis-resistant NOD mouse and the apoptosis
      susceptible C57BL/6 mouse, we define a major locus controlling the apoptosis
      resistance phenotype and demonstrate its linkage (logarithm of odds score = 3.9)
      to a group of medial markers on chromosome 1. The newly defined gene cannot be
      dissociated from Ctla4 and Cd28 and in fact marks a 20-centimorgan region
      encompassing Idd5, a previously postulated diabetes susceptibility locus.
      Interestingly, we find that the CTLA-4 (cytotoxic T lymphocyte-associated antigen
      4) and the CD28 costimulatory molecules are defectively expressed in NOD mice,
      suggesting that one or both of these molecules may be involved in the control of
      apoptosis resistance and, in turn, in diabetes susceptibility.

PMID- 9238034
TI  - Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit
      strain-specific allelic loss on mouse chromosome 4.
AB  - Hybrid mice carrying oncogenic transgenes afford powerful systems for
      investigating loss of heterozygosity (LOH) in tumors. Here, we apply this
      approach to a neoplasm of key importance in human medicine: mammary carcinoma. We
      performed a whole genome search for LOH using the mouse mammary tumor virus/v-Ha
      ras mammary carcinoma model in female (FVB/N x Mus musculus castaneus)F1 mice.
      Mammary tumors developed as expected, as well as a few tumors of a second type
      (uterine leiomyosarcoma) not previously associated with this transgene.
      Genotyping of 94 anatomically independent tumors revealed high-frequency LOH (
      approximately 38%) for markers on chromosome 4. A marked allelic bias was
      observed, with M. musculus castaneus alleles almost exclusively being lost. No
      evidence of genomic imprinting effects was noted. These data point to the
      presence of a tumor suppressor gene(s) on mouse chromosome 4 involved in mammary
      carcinogenesis induced by mutant H-ras expression, and for which a significant
      functional difference may exist between the M. musculus castaneus and FVB/N
      alleles. Provisional subchromosomal localization of this gene, designated Loh-3,
      can be made to a distal segment having syntenic correspondence to human
      chromosome 1p; LOH in this latter region is observed in several human
      malignancies, including breast cancers. Evidence was also obtained for a possible
      second locus associated with LOH with less marked allele bias on proximal
      chromosome 4.

PMID- 9238037
TI  - Cisplatin increases meiotic crossing-over in mice.
AB  - Genetic mapping of traits and mutations in mammals is dependent upon linkage
      analysis. The resolution achieved by this method is related to the number of
      offspring that can be scored and position of crossovers near a gene. Higher
      precision mapping is obtained by expanding the collection of progeny from an
      appropriate cross, which in turn increases the number of potentially informative
      recombinants. A more efficient approach would be to increase the frequency of
      recombination, rather than the number of progeny. The anticancer drug cisplatin,
      which causes DNA strand breakage and is highly recombinogenic in some model
      organisms, was tested for its ability to induce germ-line recombination in mice.
      Males were exposed to cisplatin and mated at various times thereafter to monitor
      the number of crossovers inherited by offspring. We observed a striking increase
      on all three chromosomes examined and established a regimen that nearly doubled
      crossover frequency. The timing of the response indicated that the crossovers
      were induced at the early pachytene stage of meiosis I. The ability to increase
      recombination should facilitate genetic mapping and positional cloning in mice.

PMID- 9238038
TI  - Epithelial antibiotic induced in states of disease.
AB  - Epithelial defensins provide an active defense against the external microbial
      environment. We investigated the distribution and expression of this class of
      antimicrobial peptides in normal cattle and in animals in varying states of
      disease. beta-defensin mRNA was found to be widely expressed in numerous exposed
      epithelia but was found at higher levels in tissues that are constantly exposed
      to and colonized by microorganisms. We observed induction in ileal mucosa during
      chronic infection with Mycobacterium paratuberculosis and in bronchial epithelium
      after acute infection with Pasteurella haemolytica. It has been proposed that
      expression of antimicrobial peptides is an integral component of the inflammatory
      response. The results reported here support this hypothesis and suggest that
      epithelial defensins provide a rapidly mobilized local defense against infectious
      organisms.

PMID- 9238039
TI  - A family of fibrinogen-related proteins that precipitates parasite-derived
      molecules is produced by an invertebrate after infection.
AB  - After infection with the digenetic trematode Echinostoma paraensei, hemolymph of
      the snail Biomphalaria glabrata contains lectins comprised of 65-kDa subunits
      that precipitate polypeptides secreted by E. paraensei intramolluscan larvae.
      Comparable activity is lacking in hemolymph of uninfected snails. Three different
      cDNAs with sequence similarities to peptides derived from the 65-kDa lectins were
      obtained and unexpectedly found to encode fibrinogen-related proteins (FREPs).
      These FREPs also contained regions with sequence similarity to Ig superfamily
      members. B. glabrata has at least five FREP genes, three of which are expressed
      at increased levels after infection. Elucidation of components of the defense
      system of B. glabrata is relevant because this snail is an intermediate host for
      Schistosoma mansoni, the most widely distributed causative agent of human
      schistosomiasis. These results are novel in suggesting a role for invertebrate
      FREPs in recognition of parasite-derived molecules and also provide a model for
      investigating the diversity of molecules functioning in nonself-recognition in an
      invertebrate.

PMID- 9238040
TI  - Characterization of anti-anti-idiotypic antibodies that bind antigen and an anti
      idiotype.
AB  - Two mouse monoclonal anti-anti-idiotopic antibodies (anti-anti-Id, Ab3), AF14 and
      AF52, were prepared by immunizing BALB/c mice with rabbit polyclonal anti
      idiotypic antibodies (anti-Id, Ab2) raised against antibody D1.3 (Ab1) specific
      for the antigen hen egg lysozyme. AF14 and AF52 react with an "internal image"
      monoclonal mouse anti-Id antibody E5.2 (Ab2), previously raised against D1.3,
      with affinity constants (1.0 x 10(9) M-1 and 2.4 x 10(7) M-1, respectively)
      usually observed in secondary responses against protein antigens. They also react
      with the antigen but with lower affinity (1.8 x 10(6) M-1 and 3.8 x 10(6) M-1).
      This pattern of affinities for the anti-Id and for the antigen also was displayed
      by the sera of the immunized mice. The amino acid sequences of AF14 and AF52 are
      very close to that of D1.3. In particular, the amino acid side chains that
      contribute to contacts with both antigen and anti-Id are largely conserved in
      AF14 and AF52 compared with D1.3. Therapeutic immunizations against different
      pathogenic antigens using anti-Id antibodies have been proposed. Our experiments
      show that a response to an anti-Id immunogen elicits anti-anti-Id antibodies that
      are optimized for binding the anti-Id antibodies rather than the antigen.

PMID- 9238041
TI  - Specific T cell recognition of kinetic isomers in the binding of peptide to class
      II major histocompatibility complex.
AB  - Helper T cells are triggered by molecular complexes of antigenic peptides and
      class II proteins of the major histocompatibility complex. The formation of
      stable complexes between class II major histocompatibility complex proteins and
      antigenic peptides is often accompanied by the formation of a short-lived
      complex. In this report, we describe T cell recognition of two distinct
      complexes, one short-lived and the other long-lived, formed during the binding of
      an altered myelin basic protein peptide to I-Ak. One myelin basic protein
      specific T cell clone is triggered by only the short-lived complex, and another
      is triggered by only the stable complex. Thus, a single peptide bound to a
      particular class II molecule can activate different T cells depending on the
      conditions of the binding reaction.

PMID- 9238042
TI  - Cloning and functional characterization of a subunit of the transporter
      associated with antigen processing.
AB  - The transporter associated with antigen processing (TAP) is essential for the
      transport of antigenic peptides across the membrane of the endoplasmic reticulum.
      In addition, TAP interacts with major histocompatibility complex class I heavy
      chain (HC)/beta2-microglobulin (beta2-m) dimers. We have cloned a cDNA encoding a
      TAP1/2-associated protein (TAP-A) corresponding in size and biochemical
      properties to tapasin, which was recently suggested to be involved in class I-TAP
      interaction (Sadasivan, B., Lehner, P. J., Ortmann, B., Spies, T. & Cresswell, P.
      (1996) Immunity 5, 103-114). The cDNA encodes a 448-residue-long ORF, including a
      signal peptide. The protein is predicted to be a type I membrane glycoprotein
      with a cytoplasmic tail containing a double-lysine motif (-KKKAE-COOH) known to
      maintain membrane proteins in the endoplasmic reticulum. Immunoprecipitation with
      anti-TAP1 or anti-TAP-A antisera demonstrated a consistent and stoichiometric
      association of TAP-A with TAP1/2. Class I HC and beta2-m also were coprecipitated
      with these antisera, indicating the presence of a pentameric complex. In pulse
      chase experiments, class I HC/beta2-m rapidly dissociated from TAP1/2-TAP-A. We
      propose that TAP is a trimeric complex consisting of TAP1, TAP2, and TAP-A that
      interacts transiently with class I HC/beta2-m. In peptide-binding assays using
      cross-linkable peptides and intact microsomes, TAP-A bound peptides only in the
      presence of ATP whereas binding of peptides to TAP1/2 was ATP-independent. This
      suggests a direct role of TAP-A in peptide loading onto class I HC/beta2-m dimer.

PMID- 9238043
TI  - CCAAT/enhancer binding protein (C/EBP) sites are required for HIV-1 replication
      in primary macrophages but not CD4(+) T cells.
AB  - The importance of CCAAT/enhancer binding proteins (C/EBPs) and binding sites for
      HIV-1 replication in primary macrophages, T cell lines and primary CD4(+) T cells
      was examined. When lines overexpressing the C/EBP dominant-negative protein LIP
      were infected with HIV-1, replication occurred in Jurkat T cells but not in U937
      promonocytes, demonstrating a requirement for C/EBP activators by HIV-1 only in
      promonocytes. Primary macrophages did not support the replication of HIV-1
      harboring mutant C/EBP binding sites in the long terminal repeat but Jurkat, H9
      and primary CD4(+) T cells supported replication of wild-type and mutant HIV-1
      equally well. Thus the requirement for C/EBP sites is also confined to
      monocyte/macrophages. The requirement for C/EBP proteins and sites identifies the
      first uniquely macrophage-specific regulatory mechanism for HIV-1 replication.

PMID- 9238044
TI  - Abrogation of the alternative complement pathway by targeted deletion of murine
      factor B.
AB  - To investigate the role of complement protein factor B (Bf) and alternative
      pathway activity in vivo, and to test the hypothesized potential genetic lethal
      effect of Bf deficiency, the murine Bf gene was interrupted by exchange of exon 3
      through exon 7 (including the factor D cleaving site) with the neor gene. Mice
      heterozygous for the targeted Bf allele were interbred, yielding Bf-deficient
      offspring after the F1 generation at a frequency suggesting that Bf deficiency
      alone has no major effect on fertility or fetal development. However, in the
      context of one or more genes derived from the 129 mouse strain, offspring
      homozygous for Bf deficiency were generated at less than expected numbers (P =
      0.012). Bf-deficient mice showed no gross phenotypic difference from wild-type
      littermates. Sera from Bf-deficient mice lacked detectable alternative complement
      pathway activity; purified mouse Bf overcame the deficit. Classical pathway
      dependent total hemolytic activity was lower in Bf-deficient than wild-type mice,
      possibly reflecting loss of the alternative pathway amplification loop. Lymphoid
      organ structure and IgG1 antibody response to a T-dependent antigen appeared
      normal in Bf-deficient mice. Sensitivity to lethal endotoxic shock was not
      significantly altered in Bf-deficient mice. Thus, deficiency of Bf and
      alternative complement activation pathway led to a less dramatic phenotype than
      expected. Nevertheless, these mice provide an excellent model for the assessment
      of the role of Bf and the alternative pathway in host defense and other functions
      in vivo.

PMID- 9238045
TI  - DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic
      T lymphocyte responses in neonates and during early life.
AB  - The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL)
      responses in early life is associated with an increased susceptibility to
      infections by intracellular microorganisms. This is likely to reflect a
      preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1
      pattern upon immunization with conventional vaccines. In this report, it is shown
      that a single immunization within the first week of life with DNA plasmids
      encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or
      bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like
      Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific
      antibodies and preferential secretion of interferon-gamma (IFN-gamma) compared
      with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL
      responses. However, in spite of this potent Th1-driving capacity, subsequent DNA
      immunization was not capable of reverting the Th2-biased responses induced after
      early priming with a recombinant measles canarypox vector. Thus, DNA vaccination
      represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL
      responses in neonates and early life, providing it is performed prior to exposure
      to Th2-driving conventional vaccine antigens.

PMID- 9238046
TI  - MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute
      myeloid leukemia with a t(11;16)(q23;p13.3).
AB  - The recurring translocation t(11;16)(q23;p13.3) has been documented only in cases
      of acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA
      topoisomerase II. We show that the MLL gene is fused to the gene that codes for
      CBP (CREB-binding protein), the protein that binds specifically to the DNA
      binding protein CREB (cAMP response element-binding protein) in this
      translocation. MLL is fused in-frame to a different exon of CBP in two patients
      producing chimeric proteins containing the AT-hooks, methyltransferase homology
      domain, and transcriptional repression domain of MLL fused to the CREB binding
      domain or to the bromodomain of CBP. Both fusion products retain the histone
      acetyltransferase domain of CBP and may lead to leukemia by promoting histone
      acetylation of genomic regions targeted by the MLL AT-hooks, leading to
      transcriptional deregulation via aberrant chromatin organization. CBP is the
      first partner gene of MLL containing well defined structural and functional
      motifs that provide unique insights into the potential mechanisms by which these
      translocations contribute to leukemogenesis.

PMID- 9238047
TI  - Transcripts from a single full-length cDNA clone of hepatitis C virus are
      infectious when directly transfected into the liver of a chimpanzee.
AB  - We have succeeded in constructing a stable full-length cDNA clone of strain H77
      (genotype 1a) of hepatitis C virus (HCV). We devised a cassette vector with fixed
      5' and 3' termini and constructed multiple full-length cDNA clones of H77 in a
      single step by cloning of the entire ORF, which was amplified by long reverse
      transcriptase-PCR, directly into this vector. The infectivity of two complete
      full-length cDNA clones was tested by the direct intrahepatic injection of a
      chimpanzee with RNA transcripts. However, we found no evidence for HCV
      replication. Sequence analysis of these and 16 additional full-length clones
      revealed that seven clones were defective for polyprotein synthesis, and the
      remaining nine clones had 6-28 amino acid mutations in the predicted polyprotein
      compared with the consensus sequence of H77. Next, we constructed a consensus
      chimera from four of the full-length cDNA clones with just two ligation steps.
      Injection of RNA transcripts from this consensus clone into the liver of a
      chimpanzee resulted in viral replication. The sequence of the virus recovered
      from the chimpanzee was identical to that of the injected RNA transcripts. This
      stable infectious molecular clone should be an important tool for developing a
      better understanding of the molecular biology and pathogenesis of HCV.

PMID- 9238048
TI  - Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor
      necrosis factor alpha.
AB  - Persistent infection with hepatitis B virus (HBV) is a leading cause of human
      liver disease and is strongly associated with hepatocellular carcinoma, one of
      the most prevalent forms of human cancer. Apoptosis (programmed cell death) is an
      important mediator of chronic liver disease caused by HBV infection. It is
      demonstrated that the HBV HBx protein acutely sensitizes cells to apoptotic
      killing when expressed during viral replication in cultured cells and in
      transfected cells independently of other HBV genes. Cells that were resistant to
      apoptotic killing by high doses of tumor necrosis factor alpha (TNFalpha), a
      cytokine associated with liver damage during HBV infection, were made sensitive
      to very low doses of TNFalpha by HBx. HBx induced apoptosis by prolonged
      stimulation of N-Myc and the stress-mediated mitogen-activated-protein kinase
      kinase 1 (MEKK1) pathway but not by up-regulating TNF receptors. Cell killing was
      blocked by inhibiting HBx stimulation of N-Myc or mitogen-activated-protein
      kinase kinase 1 using dominant-interfering forms or by retargeting HBx from the
      cytoplasm to the nucleus, which prevents HBx activation of cytoplasmic signal
      transduction cascades. Treatment of cells with a mitogenic growth factor produced
      by many virus-induced tumors impaired induction of apoptosis by HBx and TNFalpha.
      These results indicate that HBx might be involved in HBV pathogenesis (liver
      disease) during virus infection and that enhanced apoptotic killing by HBx and
      TNFalpha might select for neoplastic hepatocytes that survive by synthesizing
      mitogenic growth factors.

PMID- 9238049
TI  - Platelet signal transduction defect with Galpha subunit dysfunction and
      diminished Galphaq in a patient with abnormal platelet responses.
AB  - G proteins play a major role in signal transduction upon platelet activation. We
      have previously reported a patient with impaired agonist-induced aggregation,
      secretion, arachidonate release, and Ca2+ mobilization. Present studies
      demonstrated that platelet phospholipase A2 (cytosolic and membrane) activity in
      the patient was normal. Receptor-mediated activation of glycoprotein (GP) IIb
      IIIa complex measured by flow cytometry using antibody PAC-1 was diminished
      despite normal amounts of GPIIb-IIIa on platelets. Ca2+ release induced by
      guanosine 5'-[gamma-thio]triphosphate (GTP[gammaS]) was diminished in the
      patient's platelets, suggesting a defect distal to agonist receptors. GTPase
      activity (a function of alpha-subunit) in platelet membranes was normal in
      resting state but was diminished compared with normal subjects on stimulation
      with thrombin, platelet-activating factor, or the thromboxane A2 analog U46619.
      Binding of 35S-labeled GTP[gammaS] to platelet membranes was decreased under both
      basal and thrombin-stimulated states. Iloprost (a stable prostaglandin I2 analog)
      -induced rise in cAMP (mediated by Galphas) and its inhibition (mediated by
      Galphai) by thrombin in the patient's platelet membranes were normal. Immunoblot
      analysis of Galpha subunits in the patient's platelet membranes showed a decrease
      in Galphaq (<50%) but not Galphai, Galphaz, Galpha12, and Galpha13. These studies
      provide evidence for a hitherto undescribed defect in human platelet G-protein
      alpha-subunit function leading to impaired platelet responses, and they provide
      further evidence for a major role of Galphaq in thrombin-induced responses.

PMID- 9238050
TI  - Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal
      hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell
      disorder resulting from mutations in an X-linked gene, PIG-A, that encodes an
      enzyme required for the first step in the biosynthesis of
      glycosylphosphatidylinositol (GPI) anchors. PIG-A mutations result in absent or
      decreased cell surface expression of all GPI-anchored proteins. Although many of
      the clinical manifestations (e.g., hemolytic anemia) of the disease can be
      explained by a deficiency of GPI-anchored complement regulatory proteins such as
      CD59 and CD55, it is unclear why the PNH clone dominates hematopoiesis and why it
      is prone to evolve into acute leukemia. We found that PIG-A mutations confer a
      survival advantage by making cells relatively resistant to apoptotic death. When
      placed in serum-free medium, granulocytes and affected CD34(+) (CD59(-)) cells
      from PNH patients survived longer than their normal counterparts. PNH cells were
      also relatively resistant to apoptosis induced by ionizing irradiation.
      Replacement of the normal PIG-A gene in PNH cell lines reversed the cellular
      resistance to apoptosis. Inhibited apoptosis resulting from PIG-A mutations
      appears to be the principle mechanism by which PNH cells maintain a growth
      advantage over normal progenitors and could play a role in the propensity of this
      disease to transform into more aggressive hematologic disorders. These data also
      suggest that GPI anchors are important in regulating apoptosis.

PMID- 9238052
TI  - Pig but not human interferon-gamma initiates human cell-mediated rejection of pig
      tissue in vivo.
AB  - Split-thickness pig skin was transplanted on severe combined immunodeficient mice
      so that pig dermal microvessels spontaneously inosculated with mouse microvessels
      and functioned to perfuse the grafts. Pig endothelial cells in the healed grafts
      constitutively expressed class I and class II major histocompatibility complex
      molecules. Major histocompatibility complex molecule expression could be further
      increased by intradermal injection of pig interferon-gamma (IFN-gamma) but not
      human IFN-gamma or tumor necrosis factor. Grafts injected with pig IFN-gamma also
      developed a sparse infiltrate of mouse neutrophils and eosinophils without
      evidence of injury. Introduction of human peripheral blood mononuclear cells into
      the animals by intraperitoneal inoculation resulted in sparse perivascular
      mononuclear cell infiltrates in the grafts confined to the pig dermis. Injection
      of pig skin grafts on mice that received human peripheral blood mononuclear cells
      with pig IFN-gamma (but not human IFN-gamma or heat-inactivated pig IFN-gamma)
      induced human CD4(+) and CD8(+) T cells and macrophages to more extensively
      infiltrate the pig skin grafts and injure pig dermal microvessels. These findings
      suggest that human T cell-mediated rejection of xenotransplanted pig organs may
      be prevented if cellular sources of pig interferon (e.g., passenger lymphocytes)
      are eliminated from the graft.

PMID- 9238051
TI  - Conditional switching of vascular endothelial growth factor (VEGF) expression in
      tumors: induction of endothelial cell shedding and regression of hemangioblastoma
      like vessels by VEGF withdrawal.
AB  - We have recently shown that VEGF functions as a survival factor for newly formed
      vessels during developmental neovascularization, but is not required for
      maintenance of mature vessels. Reasoning that expanding tumors contain a
      significant fraction of newly formed and remodeling vessels, we examined whether
      abrupt withdrawal of VEGF will result in regression of preformed tumor vessels.
      Using a tetracycline-regulated VEGF expression system in xenografted C6 glioma
      cells, we showed that shutting off VEGF production leads to detachment of
      endothelial cells from the walls of preformed vessels and their subsequent death
      by apoptosis. Vascular collapse then leads to hemorrhages and extensive tumor
      necrosis. These results suggest that enforced withdrawal of vascular survival
      factors can be applied to target preformed tumor vasculature in established
      tumors. The system was also used to examine phenotypes resulting from over
      expression of VEGF. When expression of the transfected VEGF cDNA was continuously
      "on," tumors became hyper-vascularized with abnormally large vessels, presumably
      arising from excessive fusions. Tumors were significantly less necrotic,
      suggesting that necrosis in these tumors is the result of insufficient
      angiogenesis.

PMID- 9238054
TI  - Demonstration of a novel circulating anti-prostacyclin receptor antibody.
AB  - Although coronary artery disease (CAD) is appreciated to be accelerated in
      patients with chronic spinal cord injury (SCI), the underlying mechanism of CAD
      in SCI remains obscure. We have recently shown that platelets from subjects with
      SCI develop resistance to the inhibitory effect of prostacyclin (PGI2) on the
      platelet stimulation of thrombin generation. The loss of the inhibitory effect
      was due to the loss of high-affinity prostanoid receptors, which may contribute
      to atherogenesis in SCI. Incubation of normal, non-SCI platelets in SCI plasma (n
      = 12) also resulted in the loss of high-affinity binding of PGI2 (Kd1 = 9.1 +/-
      2.0 nM; n1 = 170 +/- 32 sites per cell vs. Kd1 = 7.2 +/- 1.1 nM; n1 = 23 +/- 8
      sites per cell), with no significant change in the low-affinity receptors (Kd2 =
      1.9 +/- 0.1 microM; n2 = 1,832 +/- 232 sites per cell vs. Kd2 = 1. 6 +/- 0.1
      microM; n2 = 1,740 +/- 161 sites per cell) as determined by Scatchard analysis of
      the binding of [3H]PGE1. The loss of high-affinity PGI2 binding led to the
      failure of PGI2 to inhibit the platelet-stimulated thrombin generation. The
      increase of cellular cyclic AMP level, mediated through the binding of PGI2 to
      low-affinity receptors in platelets, was unaffected in SCI platelets. PAGE and
      immunoblot of SCI plasma showed the presence of an IgG band, which specifically
      blocked the binding of [3H]PGE1 to the high-affinity PGI2 receptors of normal
      platelets. PAGE of the reduced IgG band, the amino acid sequence of the novel
      band as a heavy chain of IgG that inhibits the binding of [3H]PGE1 to the high
      affinity platelet PGI2 receptor, demonstrates that the specific recognition and
      inhibition of high-affinity PGI2 binding to platelets was due to an anti
      prostacyclin receptor antibody present in SCI plasma.

PMID- 9238053
TI  - Ubiquitous, heritable damage in cell populations that survive treatment with
      methotrexate.
AB  - A permanent line of mouse embryo fibroblasts was treated with concentrations of
      the anticancer drug methotrexate (MTX) that left 20-50% surviving colonies. The
      surviving population initially multiplied at a much slower rate than controls
      after subculture in the absence of the drug, and required 9-12 days of serial
      subculture, with selective growth of the faster growing cells, to approximate the
      control rate. To determine the distribution of growth rates of cells in the
      original posttreatment populations, many single cells were isolated in multiwell
      plates immediately after the treatment period, and the resulting clones were
      serially subcultured. Most of the control clones underwent about 2 population
      doublings per day (PD/D). Almost all the survivors of MTX treatment multiplied at
      heterogeneously reduced rates, ranging from 0.6 PD/D to as high as control rates
      for a very few clones. They maintained the reduced rates through many
      subcultivations. The heritability of the reduced growth rates indicates that most
      cells that retain proliferative capacity after treatment with MTX carry random
      genetic damage that is perpetuated through many divisions of their progeny.
      Similar results have been described for cells that survive x-irradiation, and
      suggest random genetic damage is a common occurrence among cells in rapidly
      growing tissues that survive cytotoxic treatment. It also occurs in serial
      subcultures of cells that had been held under the constraint of confluence for
      extended periods, which suggests that the accumulation of random genetic damage
      to somatic cells during aging of mammals underlies the reduction of growth rate
      and function of the cells that characterizes the aging process.

PMID- 9238055
TI  - Fluorescence tomographic imaging in turbid media using early-arriving photons and
      Laplace transforms.
AB  - We present a multichannel tomographic technique to detect fluorescent objects
      embedded in thick (6.4 cm) tissue-like turbid media using early-arriving photons.
      The experiments use picosecond laser pulses and a streak camera with single
      photon counting capability to provide short time resolution and high signal-to
      noise ratio. The tomographic algorithm is based on the Laplace transform of an
      analytical diffusion approximation of the photon migration process and provides
      excellent agreement between the actual positions of the fluorescent objects and
      the experimental estimates. Submillimeter localization accuracy and 4- to 5-mm
      resolution are demonstrated. Moreover, objects can be accurately localized when
      fluorescence background is present. The results show the feasibility of using
      early-arriving photons to image fluorescent objects embedded in a turbid medium
      and its potential in clinical applications such as breast tumor detection.

PMID- 9238056
TI  - CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates.
AB  - Selective inhibition of T cell costimulation using the B7-specific fusion protein
      CTLA4-Ig has been shown to induce long-term allograft survival in rodents.
      Antibodies preventing the interaction between CD40 and its T cell-based ligand
      CD154 (CD40L) have been shown in rodents to act synergistically with CTLA4-Ig. It
      has thus been hypothesized that these agents might be capable of inducing long
      term acceptance of allografted tissues in primates. To test this hypothesis in a
      relevant preclinical model, CTLA4-Ig and the CD40L-specific monoclonal antibody
      5C8 were tested in rhesus monkeys. Both agents effectively inhibited rhesus mixed
      lymphocyte reactions, but the combination was 100 times more effective than
      either drug alone. Renal allografts were transplanted into nephectomized rhesus
      monkeys shown to be disparate at major histocompatibility complex class I and
      class II loci. Control animals rejected in 5-8 days. Brief induction doses of
      CTLA4-Ig or 5C8 alone significantly prolonged rejection-free survival (20-98
      days). Two of four animals treated with both agents experienced extended (>150
      days) rejection-free allograft survival. Two animals treated with 5C8 alone and
      one animal treated with both 5C8 and CTLA4-Ig experienced late, biopsy-proven
      rejection, but a repeat course of their induction regimen successfully restored
      normal graft function. Neither drug affected peripheral T cell or B cell counts.
      There were no clinically evident side effects or rejections during treatment. We
      conclude that CTLA4-Ig and 5C8 can both prevent and reverse acute allograft
      rejection, significantly prolonging the survival of major histocompatibility
      complex-mismatched renal allografts in primates without the need for chronic
      immunosuppression.

PMID- 9238058
TI  - A natural polymorphism in beta-lactamase is a global suppressor.
AB  - A M182T substitution was discovered as a second-site suppressor of a missense
      mutation in TEM-1 beta-lactamase. The combination of the M182T substitution with
      other substitutions in the enzyme indicates the M182T substitution is a global
      suppressor of missense mutations in beta-lactamase. The M182T substitution also
      is found in natural variants of TEM-1 beta-lactamase with altered substrate
      specificity that have evolved in response to antibiotic therapy. The M182T
      substitution may have been selected in natural isolates as a suppressor of
      folding or stability defects resulting from mutations associated with drug
      resistance. This pathway of protein evolution may occur in other targets of
      antimicrobial drugs such as the HIV protease.

PMID- 9238057
TI  - Immunotargeting of liposomes to activated vascular endothelial cells: a strategy
      for site-selective delivery in the cardiovascular system.
AB  - Endothelial-selective delivery of therapeutic agents, such as drugs or genes,
      would provide a useful tool for modifying vascular function in various disease
      states. A potential molecular target for such delivery is E-selectin, an
      endothelial-specific cell surface molecule expressed at sites of activation in
      vivo and inducible in cultured human umbilical vein endothelial cells (HUVEC) by
      treatment with cytokines such as recombinant human interleukin 1beta (IL-1beta).
      Liposomes of various types (classical, sterically stabilized, cationic, pH
      sensitive), each conjugated with mAb H18/7, a murine monoclonal antibody that
      recognizes the extracellular domain of E-selectin, bound selectively and
      specifically to IL-1beta-activated HUVEC at levels up to 275-fold higher than to
      unactivated HUVEC. E-selectin-targeted immunoliposomes appeared in acidic,
      perinuclear vesicles 2-4 hr after binding to the cell surface, consistent with
      internalization via the endosome/lysosome pathway. Activated HUVEC incubated with
      E-selectin-targeted immunoliposomes, loaded with the cytotoxic agent doxorubicin,
      exhibited significantly decreased cell survival, whereas unactivated HUVEC were
      unaffected by such treatment. These results demonstrate the feasibility of
      exploiting cell surface activation markers for the endothelial-selective delivery
      of biologically active agents via immunoliposomes. Application of this targeting
      approach in vivo may lead to novel therapeutic strategies in the treatment of
      cardiovascular disease.

PMID- 9238059
TI  - Loss of virulence in Leishmania donovani deficient in an amastigote-specific
      protein, A2.
AB  - Leishmania donovani is the etiologic agent of fatal visceral leishmaniasis in
      man. During their life cycle, Leishmania exist as flagellated promastigotes
      within the sandfly vector and as nonflagellated amastigotes in the macrophage
      phagolysosomal compartment of the mammalian host. The transformation from
      promastigotes to amastigotes is a critical step for the establishment of
      infection, and the molecular basis for this transformation is poorly understood.
      To define the molecular basis for amastigote survival in the mammalian host, we
      previously identified an amastigote stage-specific gene family termed "A2." In
      the present study, we have inhibited the expression of A2 mRNA and A2 protein in
      amastigotes using antisense RNA and show that the resulting A2-deficient
      amastigotes are severely compromised with respect to virulence in mice.
      Amastigotes that did survive in the mice had restored A2 protein expression.
      These data demonstrate that A2 protein is required for L. donovani survival in a
      mammalian host, and this represents the first identified amastigote-specific
      virulence factor identified in Leishmania. This study also reveals that it is
      possible to study gene function in Leishmania through the expression of antisense
      RNA.

PMID- 9238060
TI  - Transcription initiation is controlled by three core promoter elements in the
      hgl5 gene of the protozoan parasite Entamoeba histolytica.
AB  - Entamoeba histolytica is a single cell eukaryote that is the etiologic agent of
      amoebic colitis. Core promoter elements of E. histolytica protein encoding genes
      include a TATA-like sequence (GTATTTAAAG/C) at -30, a novel element designated
      GAAC (GAACT) that has a variable location between TATA and the site of
      transcription initiation, and a putative initiator (Inr) element (AAAAATTCA)
      overlying the site of transcription initiation. The presence of three separate
      conserved sequences in a eukaryotic core promoter is unprecedented and prompted
      examination of their roles in regulating transcription initiation. Alterations of
      all three regions in the hgl5 gene decreased reporter gene activity with the
      greatest effect seen by mutation of the GAAC element. Positional analysis of the
      TATA box demonstrated that transcription initiated consistently 30-31 bases
      downstream of the TATA region. Mutation of either the TATA or GAAC elements
      resulted in the appearance of new transcription start sites upstream of +1 in the
      promoter of the hgl5 gene. Mutation of the Inr element resulted in no change in
      the site of transcription initiation; however, in the presence of a mutated TATA
      and GAAC regions, the Inr element controlled the site of transcription
      initiation. We conclude that all three elements play a role in determining the
      site of transcription initiation. The variable position of the GAAC element
      relative to the site of transcription initiation, and the multiple transcription
      initiations that resulted from its mutation, indicate that the GAAC element has
      an important and apparently novel role in transcriptional control in E.
      histolytica.

PMID- 9238061
TI  - Intrastriatal injection of an adenoviral vector expressing glial-cell-line
      derived neurotrophic factor prevents dopaminergic neuron degeneration and
      behavioral impairment in a rat model of Parkinson disease.
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic
      factor for adult nigral dopamine neurons in vivo. GDNF has both protective and
      restorative effects on the nigro-striatal dopaminergic (DA) system in animal
      models of Parkinson disease. Appropriate administration of this factor is
      essential for the success of its clinical application. Since it cannot cross the
      blood-brain barrier, a gene transfer method may be appropriate for delivery of
      the trophic factor to DA cells. We have constructed a recombinant adenovirus (Ad)
      encoding GDNF and injected it into rat striatum to make use of its ability to
      infect neurons and to be retrogradely transported by DA neurons. Ad-GDNF was
      found to drive production of large amounts of GDNF, as quantified by ELISA. The
      GDNF produced after gene transfer was biologically active: it increased the
      survival and differentiation of DA neurons in vitro. To test the efficacy of the
      Ad-mediated GDNF gene transfer in vivo, we used a progressive lesion model of
      Parkinson disease. Rats received injections unilaterally into their striatum
      first of Ad and then 6 days later of 6-hydroxydopamine. We found that
      mesencephalic nigral dopamine neurons of animals treated with the Ad-GDNF were
      protected, whereas those of animals treated with the Ad-beta-galactosidase were
      not. This protection was associated with a difference in motor function:
      amphetamine-induced turning was much lower in animals that received the Ad-GDNF
      than in the animals that received Ad-beta-galactosidase. This finding may have
      implications for the development of a treatment for Parkinson disease based on
      the use of neurotrophic factors.

PMID- 9238062
TI  - A point mutation in the gamma2 subunit of gamma-aminobutyric acid type A
      receptors results in altered benzodiazepine binding site specificity.
AB  - Benzodiazepines allosterically modulate gamma-aminobutyric acid (GABA) evoked
      chloride currents of gamma-aminobutyric acid type A (GABAA) receptors.
      Coexpression of either rat gamma2 or gamma3, in combination with alpha1 and beta2
      subunits, results both in receptors displaying high [3H]Ro 15-1788 affinity.
      However, receptors containing a gamma3 subunit display a 178-fold reduced
      affinity to zolpidem as compared with gamma2-containing receptors. Eight chimeras
      between gamma2 and gamma3 were constructed followed by nine different point
      mutations in gamma2, each to the homologous amino acid residue found in gamma3.
      Chimeric or mutant gamma subunits were coexpressed with alpha1 and beta2 in human
      embryonic kidney 293 cells to localize amino acid residues responsible for the
      reduced zolpidem affinity. Substitution of a methionine-to-leucine at position
      130 of gamma2 (gamma2M130L) resulted in a 51-fold reduction in zolpidem affinity
      whereas the affinity to [3H]Ro 15-1788 remained unchanged. The affinity for
      diazepam was only decreased by about 2-fold. The same mutation resulted in a 9
      fold increase in Cl 218872 affinity. A second mutation (gamma2M57I) was found to
      reduce zolpidem affinity by about 4-fold. Wild-type and gamma2M130L-containing
      receptors were functionally expressed in Xenopus oocytes. Upon mutation
      allosteric coupling between agonist and modulatory sites is preserved. Dose
      response curves for zolpidem and for diazepam showed that the zolpidem but not
      the diazepam apparent affinity is drastically reduced. The apparent GABA affinity
      is not significantly affected by the gamma2M130L mutation. The identified amino
      acid residues may define part of the benzodiazepine binding pocket of GABAA
      receptors. As the modulatory site in the GABAA receptor is homologous to the GABA
      site, and to all agonist sites of related receptors, gamma2M130 may either point
      to a homologous region important for agonist binding in all receptors or define a
      new region not underlying this principle.

PMID- 9238063
TI  - Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes.
AB  - In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have
      analyzed the expression of ionotropic glutamate receptor subunits as well as the
      effect of the activation of these receptors on oligodendrocyte viability. Reverse
      transcription-PCR, in combination with immunocytochemistry, demonstrated that
      most oligodendrocytes differentiated in vitro express the alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the
      kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure
      to kainate caused extensive oligodendrocyte death in culture. This effect was
      partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely
      abolished by the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate
      receptors mediate the observed kainate toxicity. Furthermore, chronic application
      of kainate to optic nerves in vivo resulted in massive oligodendrocyte death
      which, as in vitro, could be prevented by coinfusion of the toxin with CNQX.
      These findings suggest that excessive activation of the ionotropic glutamate
      receptors expressed by oligodendrocytes may act as a negative regulator of the
      size of this cell population.

PMID- 9238064
TI  - Modulation of cognition-specific cortical activity by gonadal steroids: a
      positron-emission tomography study in women.
AB  - There is considerable evidence from animal studies that gonadal steroid hormones
      modulate neuronal activity and affect behavior. To study this in humans directly,
      we used H215O positron-emission tomography to measure regional cerebral blood
      flow (rCBF) in young women during three pharmacologically controlled hormonal
      conditions spanning 4-5 months: ovarian suppression induced by the gonadotropin
      releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol
      replacement, and Lupron plus progesterone replacement. Estradiol and progesterone
      were administered in a double-blind cross-over design. On each occasion positron
      emission tomography scans were performed during (i) the Wisconsin Card Sorting
      Test, a neuropsychological test that physiologically activates prefrontal cortex
      (PFC) and an associated cortical network including inferior parietal lobule and
      posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample
      sensorimotor control task. During treatment with Lupron alone (i.e., with virtual
      absence of gonadal steroid hormones), there was marked attenuation of the typical
      Wisconsin Card Sorting Test activation pattern even though task performance did
      not change. Most strikingly, there was no rCBF increase in PFC. When either
      progesterone or estrogen was added to the Lupron regimen, there was normalization
      of the rCBF activation pattern with augmentation of the parietal and temporal
      foci and return of the dorsolateral PFC activation. These data directly
      demonstrate that the hormonal milieu modulates cognition-related neural activity
      in humans.

PMID- 9238065
TI  - A calcium responsive element that regulates expression of two calcium binding
      proteins in Purkinje cells.
AB  - Calbindin D28 encodes a calcium binding protein that is expressed in the
      cerebellum exclusively in Purkinje cells. We have used biolistic transfection of
      organotypic slices of P12 cerebellum to identify a 40-bp element from the
      calbindin promoter that is necessary and sufficient for Purkinje cell specific
      expression in this transient in situ assay. This element (PCE1) is also present
      in the calmodulin II promoter, which regulates expression of a second Purkinje
      cell Ca2+ binding protein. Expression of high levels of exogenous calbindin or
      calretinin decreased transcription mediated by PCE1 in Purkinje cells 2.5- to 3
      fold, whereas the presence of 1 microM ionomycin in the extracellular medium
      increased expression. These results demonstrate that PCE1 is a component of a
      cell-specific and Ca2+-sensitive transcriptional regulatory mechanism that may
      play a key role in setting the Ca2+ buffering capacity of Purkinje cells.

PMID- 9238066
TI  - Kinase domain of the muscle-specific receptor tyrosine kinase (MuSK) is
      sufficient for phosphorylation but not clustering of acetylcholine receptors:
      required role for the MuSK ectodomain?
AB  - Formation of the neuromuscular junction (NMJ) depends upon a nerve-derived
      protein, agrin, acting by means of a muscle-specific receptor tyrosine kinase,
      MuSK, as well as a required accessory receptor protein known as MASC. We report
      that MuSK does not merely play a structural role by demonstrating that MuSK
      kinase activity is required for inducing acetylcholine receptor (AChR)
      clustering. We also show that MuSK is necessary, and that MuSK kinase domain
      activation is sufficient, to mediate a key early event in NMJ formation
      phosphorylation of the AChR. However, MuSK kinase domain activation and the
      resulting AChR phosphorylation are not sufficient for AChR clustering; thus we
      show that the MuSK ectodomain is also required. These results indicate that AChR
      phosphorylation is not the sole trigger of the clustering process. Moreover, our
      results suggest that, unlike the ectodomain of all other receptor tyrosine
      kinases, the MuSK ectodomain plays a required role in addition to simply
      mediating ligand binding and receptor dimerization, perhaps by helping to recruit
      NMJ components to a MuSK-based scaffold.

PMID- 9238067
TI  - Nucleus reticularis neurons mediate diverse inhibitory effects in thalamus.
AB  - Detailed information regarding the contribution of individual gamma-aminobutyric
      acid (GABA)-containing inhibitory neurons to the overall synaptic activity of
      single postsynaptic cells is essential to our understanding of fundamental
      elements of synaptic integration and operation of neuronal circuits. For example,
      GABA-containing cells in the thalamic reticular nucleus (nRt) provide major
      inhibitory innervation of thalamic relay nuclei that is critical to
      thalamocortical rhythm generation. To investigate the contribution of individual
      nRt neurons to the strength of this internuclear inhibition, we obtained whole
      cell recordings of unitary inhibitory postsynaptic currents (IPSCs) evoked in
      ventrobasal thalamocortical (VB) neurons by stimulation of single nRt cells in
      rat thalamic slices, in conjunction with intracellular biocytin labeling. Two
      types of monosynaptic IPSCs could be distinguished. "Weak" inhibitory connections
      were characterized by a significant number of postsynaptic failures in response
      to presynaptic nRt action potentials and relatively small IPSCs. In contrast,
      "strong" inhibition was characterized by the absence of postsynaptic failures and
      significantly larger unitary IPSCs. By using miniature IPSC amplitudes to infer
      quantal size, we estimated that unitary IPSCs associated with weak inhibition
      resulted from activation of 1-3 release sites, whereas stronger inhibition would
      require simultaneous activation of 5-70 release sites. The inhibitory strengths
      were positively correlated with the density of axonal swellings of the
      presynaptic nRt neurons, an indicator that characterizes different nRt axonal
      arborization patterns. These results demonstrate that there is a heterogeneity of
      inhibitory interactions between nRt and VB neurons, and that variations in gross
      morphological features of axonal arbors in the central nervous system can be
      associated with significant differences in postsynaptic response characteristics.

PMID- 9238068
TI  - Mechanisms of spectral tuning in the mouse green cone pigment.
AB  - Diversification of cone pigment spectral sensitivities during evolution is a
      prerequisite for the development of color vision. Previous studies have
      identified two naturally occurring mechanisms that produce variation among
      vertebrate pigments by red-shifting visual pigment absorbance: addition of
      hydroxyl groups to the putative chromophore binding pocket and binding of
      chloride to a putative extracellular loop. In this paper we describe the use of
      two blue-shifting mechanisms during the evolution of rodent long-wave cone
      pigments. The mouse green pigment belongs to the long-wave subfamily of cone
      pigments, but its absorption maximum is 508 nm, similar to that of the rhodopsin
      subfamily of visual pigments, but blue-shifted 44 nm relative to the human red
      pigment, its closest homologue. We show that acquisition of a hydroxyl group near
      the retinylidene Schiff base and loss of the chloride binding site mentioned
      above fully account for the observed blue shift. These data indicate that the
      chloride binding site is not a universal attribute of long-wave cone pigments as
      generally supposed, and that, depending upon location, hydroxyl groups can alter
      the environment of the chromophore to produce either red or blue shifts.

PMID- 9238069
TI  - Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of
      the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G
      protein-coupled receptors.
AB  - Several classes of voltage-gated Ca2+ channels (VGCCs) are inhibited by G
      proteins activated by receptors for neurotransmitters and neuromodulatory
      peptides. Evidence has accumulated to indicate that for non-L-type Ca2+ channels
      the executing arm of the activated G protein is its betagamma dimer (Gbetagamma).
      We report below the existence of two Gbetagamma-binding sites on the A-, B-, and
      E-type alpha1 subunits that form non-L-type Ca2+ channels. One, reported
      previously, is in loop 1 connecting transmembrane domains I and II. The second is
      located approximately in the middle of the ca. 600-aa-long C-terminal tails. Both
      Gbetagamma-binding regions also bind the Ca2+ channel beta subunit (CCbeta),
      which, when overexpressed, interferes with inhibition by activated G proteins.
      Replacement in alpha1E of loop 1 with that of the G protein-insensitive and
      Gbetagamma-binding-negative loop 1 of alpha1C did not abolish inhibition by G
      proteins, but the exchange of the alpha1E C terminus with that of alpha1C did.
      This and properties of alpha1E C-terminal truncations indicated that the
      Gbetagamma-binding site mediating the inhibition of Ca2+ channel activity is the
      one in the C terminus. Binding of Gbetagamma to this site was inhibited by an
      alpha1-binding domain of CCbeta, thus providing an explanation for the functional
      antagonism existing between CCbeta and G protein inhibition. The data do not
      support proposals that Gbetagamma inhibits alpha1 function by interacting with
      the site located in the loop I-II linker. These results define the molecular
      mechanism by which presynaptic G protein-coupled receptors inhibit
      neurotransmission.

PMID- 9238070
TI  - Activation and inhibition of K-ATP currents by guanine nucleotides is mediated by
      different channel subunits.
AB  - The ATP-sensitive potassium channel (K-ATP channel) plays a key role in insulin
      secretion from pancreatic beta-cells. It is closed by glucose metabolism, which
      stimulates secretion, and opened by the drug diazoxide, which inhibits insulin
      release. Metabolic regulation is mediated by changes in ATP and MgADP
      concentration, which inhibit and potentiate channel activity, respectively. The
      beta-cell K-ATP channel consists of a pore-forming subunit, Kir6.2, and a
      regulatory subunit, SUR1. The site at which ATP mediates channel inhibition lies
      on Kir6.2, while the potentiatory action of MgADP involves the nucleotide-binding
      domains of SUR1. K-ATP channels are also activated by MgGTP and MgGDP.
      Furthermore, both nucleotides support the stimulatory actions of diazoxide. It is
      not known, however, whether guanine nucleotides mediate their effects by direct
      interaction with one or more of the K-ATP channel subunits or indirectly via a
      GTP-binding protein. We used a truncated form of Kir6.2, which expresses
      independently of SUR1, to show that GTP blocks K-ATP currents by interaction with
      Kir6.2 and that the potentiatory effects of GTP are endowed by SUR1. We also
      showed that mutation of the lysine residue in the Walker A motif of either the
      first (K719A) or second (K1384M) nucleotide-binding domain of SUR1 abolished both
      the potentiatory effects of GTP and GDP on K-ATP currents and their ability to
      support stimulation by diazoxide. This argues that the stimulatory effects of
      guanine nucleotides require the presence of both Walker A lysines.

PMID- 9238071
TI  - Physiological response to long-term peripheral and central leptin infusion in
      lean and obese mice.
AB  - Recent data have identified leptin as an afferent signal in a negative-feedback
      loop regulating the mass of the adipose tissue. High leptin levels are observed
      in obese humans and rodents, suggesting that, in some cases, obesity is the
      result of leptin insensitivity. This hypothesis was tested by comparing the
      response to peripherally and centrally administered leptin among lean and three
      obese strains of mice: diet-induced obese AKR/J, New Zealand Obese (NZO), and Ay.
      Subcutaneous leptin infusion to lean mice resulted in a dose-dependent loss of
      body weight at physiologic plasma levels. Chronic infusions of leptin
      intracerebroventricularly (i.c.v.) at doses of 3 ng/hr or greater resulted in
      complete depletion of visible adipose tissue, which was maintained throughout 30
      days of continuous i.c.v. infusion. Direct measurement of energy balance
      indicated that leptin treatment did not increase total energy expenditure but
      prevented the decrease that follows reduced food intake. Diet-induced obese mice
      lost weight in response to peripheral leptin but were less sensitive than lean
      mice. NZO mice were unresponsive to peripheral leptin but were responsive to
      i.c.v. leptin. Ay mice did not respond to subcutaneous leptin and were 1/100 as
      sensitive to i.c.v. leptin. The decreased response to leptin in diet-induced
      obese, NZO, and Ay mice suggests that obesity in these strains is the result of
      leptin resistance. In NZO mice, leptin resistance may be the result of decreased
      transport of leptin into the cerebrospinal fluid, whereas in Ay mice, leptin
      resistance probably results from defects downstream of the leptin receptor in the
      hypothalamus.

PMID- 9238072
TI  - Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2.
AB  - Proteinase-activated receptor 2 (PAR-2) is a recently characterized G-protein
      coupled receptor that is cleaved and activated by pancreatic trypsin. Trypsin is
      usually considered a digestive enzyme in the intestinal lumen. We examined the
      hypothesis that trypsin, at concentrations normally present in the lumen of the
      small intestine, is also a signaling molecule that specifically regulates
      enterocytes by activating PAR-2. PAR-2 mRNA was highly expressed in the mucosa of
      the small intestine and in an enterocyte cell line. Immunoreactive PAR-2 was
      detected at the apical membrane of enterocytes, where it could be cleaved by
      luminal trypsin. Physiological concentrations of pancreatic trypsin and a peptide
      corresponding to the tethered ligand of PAR-2, which is exposed by trypsin
      cleavage, stimulated generation of inositol 1,4,5-trisphosphate, arachidonic acid
      release, and secretion of prostaglandin E2 and F1alpha from enterocytes and a
      transfected cell line. Application of trypsin to the apical membrane of
      enterocytes and to the mucosal surface of everted sacs of jejunum also stimulated
      prostaglandin E2 secretion. Thus, luminal trypsin activates PAR-2 at the apical
      membrane of enterocytes to stimulate secretion of eicosanoids, which regulate
      multiple cell types in a paracrine and autocrine manner. We conclude that trypsin
      is a signaling molecule that specifically regulates enterocytes by triggering PAR
      2.

PMID- 9238076
TI  - Mendel's dwarfing gene: cDNAs from the Le alleles and function of the expressed
      proteins.
AB  - The major gibberellin (GA) controlling stem elongation in pea (Pisum sativum L.)
      is GA1, which is formed from GA20 by 3beta-hydroxylation. This step, which limits
      GA1 biosynthesis in pea, is controlled by the Le locus, one of the original
      Mendelian loci. Mutations in this locus result in dwarfism. We have isolated
      cDNAs encoding a GA 3beta-hydroxylase from lines of pea carrying the Le, le, le
      3, and led alleles. The cDNA sequences from le and le-3 each contain a base
      substitution resulting in single amino acid changes relative to the sequence from
      Le. The cDNA sequence from led, a mutant derived from an le line, contains both
      the le "mutation" and a single-base deletion, which causes a shift in reading
      frame and presumably a null mutation. cDNAs from each line were expressed in
      Escherichia coli. The expression product for the clone from Le converted GA9 to
      GA4, and GA20 to GA1, with Km values of 1.5 microM and 13 microM, respectively.
      The amino acid substitution in the clone from le increased Km for GA9 100-fold
      and reduced conversion of GA20 to almost nil. Expression products from le and le
      3 possessed similar levels of 3beta-hydroxylase activity, and the expression
      product from led was inactive. Our results suggest that the 3beta-hydroxylase
      cDNA is encoded by Le. Le transcript is expressed in roots, shoots, and
      cotyledons of germinating pea seedlings, in internodes and leaves of established
      seedlings, and in developing seeds.

PMID- 9238074
TI  - Cloning and characterization of a plastidal and a mitochondrial isoform of
      tobacco protoporphyrinogen IX oxidase.
AB  - Protoporphyrinogen IX oxidase is the last enzyme in the common pathway of heme
      and chlorophyll synthesis and provides precursor for the mitochondrial and
      plastidic heme synthesis and the predominant chlorophyll synthesis in plastids.
      We cloned two different, full-length tobacco cDNA sequences by complementation of
      the protoporphyrin-IX-accumulating Escherichia coli hemG mutant from heme
      auxotrophy. The two sequences show similarity to the recently published
      Arabidopsis PPOX, Bacillus subtilis hemY, and to mammalian sequences encoding
      protoporphyrinogen IX oxidase. One cDNA sequence encodes a 548-amino acid
      residues protein with a putative transit sequence of 50 amino acid residues, and
      the second cDNA encodes a protein of 504 amino acid residues. Both deduced
      protein sequences share 27.2% identical amino acid residues. The first in vitro
      translated protoporphyrinogen IX oxidase could be translocated to plastids, and
      the approximately 53-kDa mature protein was detected in stroma and membrane
      fraction. The second enzyme was targeted to mitochondria without any detectable
      reduction in size. Localization of both enzymes in subcellular fractions was
      immunologically confirmed. Steady-state RNA analysis indicates an almost
      synchronous expression of both genes during tobacco plant development, greening
      of young seedlings, and diurnal and circadian growth. The mature plastidal and
      the mitochondrial isoenzyme were overexpressed in E. coli. Bacterial extracts
      containing the recombinant mitochondrial enzyme exhibit high protoporphyrinogen
      IX oxidase activity relative to control strains, whereas the plastidal enzyme
      could only be expressed as an inactive peptide. The data presented confirm a
      compartmentalized pathway of tetrapyrrole synthesis with protoporphyrinogen IX
      oxidase in plastids and mitochondria.

PMID- 9238077
TI  - Philopatry of male marine turtles inferred from mitochondrial DNA markers.
AB  - Recent studies of mitochondrial DNA (mtDNA) variation among marine turtle
      populations are consistent with the hypothesis that females return to beaches in
      their natal region to nest as adults. In contrast, less is known about breeding
      migrations of male marine turtles and whether they too are philopatric to natal
      regions. Studies of geographic structuring of restriction fragment and
      microsatellite polymorphisms at anonymous nuclear loci in green turtle (Chelonia
      mydas) populations indicate that nuclear gene flow is higher than estimates from
      mtDNA analyses. Regional populations from the northern and southern Great Barrier
      Reef were distinct for mtDNA but indistinguishable at nuclear loci, whereas the
      Gulf of Carpentaria (northern Australia) population was distinct for both types
      of marker. To assess whether this result was due to reduced philopatry of males
      across the Great Barrier Reef, we determined the mtDNA haplotypes of breeding
      males at courtship areas for comparison with breeding females from the same three
      locations. We used a PCR-restriction fragment length polymorphism approach to
      determine control region haplotypes and designed mismatch primers for the
      identification of specific haplotypes. The mtDNA haplotype frequencies were not
      significantly different between males and females at any of the three areas and
      estimates of Fst among the regions were similar for males and females (Fst = 0.78
      and 0.73, respectively). We conclude that breeding males, like females, are
      philopatric to courtship areas within their natal region. Nuclear gene flow
      between populations is most likely occurring through matings during migrations of
      both males and females through nonnatal courtship areas.

PMID- 9238078
TI  - Experience-dependent, asymmetric expansion of hippocampal place fields.
AB  - Theories of sequence learning based on temporally asymmetric, Hebbian long-term
      potentiation predict that during route learning the spatial firing distributions
      of hippocampal neurons should enlarge in a direction opposite to the animal's
      movement. On a route AB, increased synaptic drive from cells representing A would
      cause cells representing B to fire earlier and more robustly. These effects
      appeared within a few laps in rats running on closed tracks. This provides
      indirect evidence for Hebbian synaptic plasticity and a functional explanation
      for why place cells become directionally selective during route following,
      namely, to preserve the synaptic asymmetry necessary to encode the sequence
      direction.

PMID- 9238079
TI  - Peptide sequences for beta-crystallins of a teleost fish.

PMID- 9238080
TI  - Fine mapping of the usher syndrome type IC to chromosome 11p14 and identification
      of flanking markers by haplotype analysis.
AB  - PURPOSE: To refine the map position of the Usher syndrome type 1C (USH1C) locus
      to 11p14-p15.1 in the French-Acadian population settled in Louisiana. METHODS:
      Linkage and haplotype analysis of Ush1C in the French-Acadian families from
      southwestern Louisiana was carried out using additional markers known to map to
      the USH1C interval. Markers localized to 11p were also mapped on the J1 somatic
      cell hybrid panel. This analysis also helped to localize precisely the USH1C
      interval. RESULTS: New flanking markers for USH1C have been identified,
      localizing the USH1C gene to a 1 cM interval between markers D11S1397 and
      D11S1888. Markers D11S1890 and D11S1888 were placed within the USH1C interval.
      Analysis of all the markers in the USH1C region flanked by D11S1397 and D11S1888
      on the J1 somatic cell hybrid panel localized USH1C to the upper half of
      chromosome 11p14. CONCLUSION: The Usher Syndrome type 1C gene has been localized
      to a 1 cM interval between the markers D11S1397 and D11S1888 on chromosome 11p14.

PMID- 9238082
TI  - Isolation of differentially expressed human fovea genes: candidates for macular
      disease.
AB  - PURPOSE: In humans, the fovea is the region of the retina responsible for acute
      vision. Disorders affecting the fovea are responsible for the majority of cases
      of untreated blindness in the developed world, yet are poorly understood at the
      molecular level. Our goal is to identify genes that are preferentially expressed
      within the human fovea as compared to the midperipheral retina (differential
      fovea clones). MATERIALS AND METHODS: An unamplified fovea cDNA library was
      differentially screened with cDNA probes derived from either human fovea or
      midperipheral retina. Rounds of secondary screening and northern analysis were
      used to verify the expression pattern of a selective number of clones isolated.
      RESULTS: Forty-one differential fovea clones were isolated from a screening of
      10,000 phage clones (clones). Of these clones, 31.5 % correspond to known
      sequences present in GenBank/EMBL and 70.7% represent novel human fovea expressed
      sequence tags (ESTs). Northern analysis of selected clones demonstrated that they
      represent genes expressed at higher levels in the human fovea than in the
      midperipheral retina. CONCLUSIONS: Genes that are more highly expressed in the
      fovea as opposed to the midperipheral retina are likely to represent essential
      genes for fovea function. Using our fovea cDNA library, we are able to isolate
      differential human fovea clones at an incidence of 41/10,000 clones screened. We
      demonstrate that there is a high level of differential gene expression within
      different regions of the human retina.

PMID- 9238081
TI  - A polymorphic trinucleotide repeat at DXS8170 in the critical region of X-linked
      retinitis pigmentosa locus RP3 at Xp21.1.

PMID- 9238083
TI  - Genetic heterogeneity in autosomal dominant pattern dystrophy of the retina.
AB  - PURPOSE: Mutations in the retinal degeneration slow (RDS)/peripherin gene have
      been shown to be associated with pattern dystrophy of the retina (PDR) and other
      retinal dystrophies. The aim of our study was to confirm or exclude the RDS locus
      and the rhodopsin (RHO) locus as the disease causing locus in a large Swiss
      family affected with pattern dystrophy of the retina. MATERIALS AND METHODS: A
      Swiss family with 14 members across 3 generations affected with PDR was examined.
      Eleven living family members were investigated using 6 markers surrounding the
      RDS and RHO loci. RESULTS: Linkage to two possible candidate genes, the RDS gene
      on chromosome 6p and the rhodopsin gene on chromosome 3q, could be excluded.
      CONCLUSIONS: The family provides evidence for genetic heterogeneity of PDR and is
      in agreement with heterogeneity in other retinal dystrophies. Further
      investigations are in progress to map the gene causing PDR in this family.

PMID- 9238084
TI  - Long term light-induced retinal degeneration in the miniature pig.
AB  - In developing a model of slow light-induced retinal degeneration, ten miniature
      pigs were submitted to constant lighting for a period ranging from one to three
      months. Post-lighting survival time ranged from zero to two months. Control and
      illuminated animals were examined for pupillary reflex, underwent fundus
      examination and an electroretinogram. After euthanasia, retinas were processed
      for histology with measure of outer nuclear layer thickness. All animals
      illuminated one or more months had pupillar reflex alteration. Mean outer nuclear
      thickness was 24.12 microns in the control and ranged from 18.36 to 21.45 microns
      in illuminated animals (mean reduction 20%). Despite the pigmentation of
      miniature pigs, consistent results were obtained in the absence of pharmacologic
      pupil dilation.

PMID- 9238085
TI  - Lack of DNase I mRNA sequences in murine lenses.
AB  - Clarity of the mammalian lens is due in part to the complete lack of internal
      organelles, including nuclei, within the lens fiber cells that compose the bulk
      of the lens. Experimental evidence shows that as the differentiation of lens
      fiber cells progresses, nuclei and nuclear DNA are actively degraded. Prior
      characterization of chick lens development suggests that DNase I could be
      involved in lens DNA degredation. However, recent data suggest that DNase I is
      unlikely to be the nuclease responsible for DNA degredation in the
      differentiating lens. In this report, we find that in the murine lens, mRNA for
      DNase I is undetectable by northern blotting or PCR. We conclude that mRNA for
      DNase I is either not present or present in very low levels in murine lens. Our
      results are consistent with the hypothesis that DNase I is not involved in lens
      DNA degredation.

PMID- 9238086
TI  - Non-uniform distribution of the NMDAR1 receptor subunit in kitten visual cortex
      at the peak of the critical period.
AB  - PURPOSE: The development of columnar systems in the visual cortex, in particular
      ocular dominance columns, is dependent on experiential activity in conjunction
      with NMDA-mediated plasticity mechanisms. Recent experiments, however, have shown
      that certain aspects of the columnar organization of the visual cortex, such as
      the spacing of columns, are not changed by manipulations that affect the pattern
      of retinal activity. This raises the possibility that features intrinsic to the
      visual cortex may play a crucial role in the development of cortical columns and
      that a non-uniform distribution of NMDA receptors in the developing visual cortex
      could form the link between activity and intrinsic cortical modularity. METHODS:
      To examine this possibility we used immunohistochemical techniques to label the
      NMDAR1 receptor subunit protein in kitten visual cortex. The arrangement of the
      NMDAR1 subunit was visualized (using a monoclonal antibody) in flattened and
      coronal sections through visual cortex. The tangential and laminar distributions
      of NMDAR1 immunoreactivity (NMDAR1ir) were studied at the peak of the critical
      period for plasticity (4-5 weeks of age) in the developing kitten visual cortex.
      RESULTS: At the ages examined there was a non-uniform distribution of NMDAR1
      immunoreactivity in the visual cortex. These patches of darker NMDAR1 label were
      found in layers 2/3 and extended up into layer 1. Thus, during development
      neurons expressing the NMDAR1 receptor subunit were distributed in a patchy
      fashion in the upper layers of the kitten visual cortex. CONCLUSIONS: This
      suggests that NMDA-mediated activity-dependent plasticity may not occur uniformly
      across the tangential extent of the visual cortex, and raises the possibility
      that the arrangement of NMDAR1 patches may guide the emergence of nascent columns
      in the developing visual cortex.

PMID- 9238087
TI  - A homozygous PDE6B mutation in a family with autosomal recessive retinitis
      pigmentosa.

PMID- 9238088
TI  - Organization, evolutionary conservation, expression and unusual Alu density of
      the human gene for pigment epithelium-derived factor, a unique neurotrophic
      serpin.
AB  - PEDF is a neurotrophic serpin that promotes a neuronal phenotype and augments
      neuronal cell survival. The isolation, sequence and structural analysis of the
      human PEDF gene and its promoter along with its evolutionary conservation and
      expression in human tissues are now described. The gene spans approximately 16 kb
      and is divided among 8 exons and 7 introns, the junctions of which conform to the
      AG/GT consensus rule. PEDF appears to fall into the ovalbumin/PAI-2 subgrouping
      of serpins and is structurally far different from GDN/PN-1, the only other
      neurotrophic serpin reported to date. The immediate 5'-flanking region is
      dominated by a dense cluster of Alu repeats in which are embedded several
      promoter consensus sequences. A CAAT box is present at -43. The putative promoter
      region is also far different from that reported for GDN/PN-1. Comparable
      hybridization signals of 23 kb EcoRI fragments containing the PEDF gene are
      observed by Southern blot analysis in all primate, mammal and avian species
      examined; conservation is particularly evident among the primates. Northern blot
      analysis confirms the presence of the PEDF transcript in a broad range of human
      fetal and adult tissues including almost all brain areas examined, underscoring
      differences with GDN/PN-1 which, in the adult brain, is only expressed in glia
      and a subset of neurons.

PMID- 9238089
TI  - Structure determination of the fourth cytoplasmic loop and carboxyl terminal
      domain of bovine rhodopsin.
AB  - PURPOSE: High resolution structural information is lacking for any member of the
      class of G-protein receptors. This dearth of structural information extends to
      virtually all integral membrane proteins. As part of an alternative approach to
      examining integral membrane protein structure, we are determining the structures
      of the extramembraneous domains of the G-protein receptor, rhodopsin. METHODS:
      The carboxyl terminal domain of bovine rhodopsin was synthesized, containing the
      last 43 amino acids of the protein sequence (rhoIVe). This sequence included the
      entire putative fourth cytoplasmic loop as well as a significant portion of helix
      seven, the transmembrane helix of this receptor to which the carboxyl terminal is
      attached. The solution structure of rhoIVe was determined by multidimensional 1H
      nuclear magnetic resonance. RESULTS: The structure contained a portion of alpha
      helix corresponding to the top of transmembrane helix seven of the receptor. This
      allowed unambiguous docking of the carboxyl terminal domain to a model of the
      transmembrane domain. Helix seven is longer than suggested by hydropathy
      analysis. The structure also revealed the fourth cytoplasmic loop. The
      palmitoylation sites of rhodopsin are located near the deduced membrane surface.
      However, palmitoylation is not required for formation of this loop. CONCLUSIONS:
      The carboxyl terminal of rhodopsin forms a structural domain whose structure can
      be determined separately from the rest of the protein. This structure reveals the
      fourth cytoplasmic loop that had been suggested to exist based on the presence of
      palmitoylation sites in the carboxyl terminal domain. Determination of the
      structure of all of the cytoplasmic domains of rhodopsin in a manner that allows
      docking to the structure of the transmembrane domain should permit construction
      of the entire surface of rhodopsin that interacts with the G-protein, transducin.
      Additionally, the rhodopsin phosphorylation sites and mutations associated with
      certain autosomal dominant forms of retinitis pigmentosa can now be located in
      the three dimensional structure of the carboxyl terminal domain.

PMID- 9238090
TI  - North Carolina macular dystrophy phenotype in France maps to the MCDR1 locus.
AB  - PURPOSE: To determine if a family in France, which manifests an autosomal
      dominant macular dystrophy, has North Carolina macular dystrophy (MCDR1) and to
      determine its possible molecular genetic relationship with the original North
      Carolina family. METHODS: A family from Northern France with a macular dystrophy
      underwent comprehensive ophthalmic examinations and were ascertained for genetic
      studies. Blood collection and examinations were performed on 38 individuals.
      Fundus photographs with a hand held KOWA camera were obtained on affected
      subjects. DNA was extracted and genotyping performed using new microsatellite
      genetic markers, which have recently been found in the MCDR1 (North Carolina
      macular dystrophy) region. Standard two - point linkage and haplotype analysis
      was performed. RESULTS: Eleven individuals were found with the clinical
      manifestations of North Carolina macular dystrophy. Two - point linkage analysis
      generated a maximum peak LOD score of 4.5 with a recombination of 0% between
      D6S1717 and the macular dystrophy locus in the French family. The haplotype
      associated with the disease is, however, different from that of the original
      North Carolina family. CONCLUSIONS: These findings indicate that the macular
      dystrophy gene in this French family maps to the same region as that of North
      Carolina macular dystrophy (MCDR1) locus but that independent mutations are
      involved. The disease in the French family is clinically and genetically similar
      to North Carolina macular dystrophy. Therefore MCDR1 occurs in various ethnic
      groups, is present world-wide, and there remains no evidence of genetic
      heterogeneity for this clinically distinct form of macular degeneration.

PMID- 9238091
TI  - Light microscopic variation of fiber cell size, shape and ordering in the
      equatorial plane of bovine and human lenses.
AB  - PURPOSE: A rapid means was sought to visualize and quantify the cross-sectional
      areas of fiber cells, the variations of cell area, and the regularity of packing
      in the equatorial plane of normal adult bovine and normal aged human lenses.
      METHODS: Vibratome sections of bovine and human lenses were fixed, embedded in LR
      White resin, and sectioned for light microscopic observation. Image analysis was
      performed to determine the cross-sectional areas of fiber cells in selected
      nuclear regions. RESULTS: Examination of bovine lenses revealed a pattern of cell
      size and shape in each region that was similar to that recently reported for
      normal human lenses (1). In the equatorial plane of bovine lenses, average cross
      sectional areas were 20 +/- 6 micron2 in the adult nucleus, 43 +/- 19 micron2 in
      the fetal nucleus, and 63 +/- 61 micron2 in the embryonic nucleus. Light
      microscopy of human lenses was consistent with our previous electron microscopic
      observations. Moreover, in both bovine and human lenses, the distribution of cell
      sizes and the number of cell layers was readily available for each region.
      Overviews of the equatorial plane demonstrated a gradual improvement in the
      regular packing of radial cell columns proceeding from the relatively disordered
      embryonic and fetal nuclei through the well-ordered adult nucleus to the highly
      regular cortical region. CONCLUSIONS: Light microscopy revealed the highly
      irregular packing and large average size of cells in the embryonic nucleus and
      the gradual reduction in size and progressive improvements in regularity of
      packing in the outer layers. The methods used here have the advantage of rapidly
      giving a continuous view of the fiber cell structure and arrangement which is not
      available using electron microscopy.

PMID- 9238092
TI  - How might 12 (R) HETE cause the inhibition of Na,K-ATPase?
AB  - PURPOSE: 12 (R) hydroxy 5,8,10,14-eicosatetraenoic acid [12 (R) HETE] is a potent
      inhibitor of Na,K-ATPase. This study was an attempt to determine how the
      eicosanoid might inhibit the enzyme by using molecular modeling. METHODS: Models
      were generated using the program HyperChem 2.0 for Windows. Models of 12 (R)
      HETE, 12 (S) HETE (the "S" isomer of 12 (R) HETE), and 8 (R) hydroxy
      hexadecatrienoic acid [8 (R) HHDTrE, a catabolic isomer of 12 (R) HETE] were
      formed and docked with phosphatidyl choline and the H3-H4 peptide of the alpha
      subunit of Na,K-ATPase. In addition, models of 12 (R) HETE, and related
      compounds, were formed and complexed with calcium, and then docked with
      phosphatidyl choline. The energies of stabilization were calculated for each
      optimal docking. RESULTS: Optimal steric fitting and calculated energies of
      stabilization indicated that 12 (R) HETE and 8 (R) HHDTrE had the best fits when
      bound to the fatty acid portions of phosphatidyl choline. However, when Ca-HETE
      complexes were modeled, it was found that they formed even more stable complexes
      when bound to phosphatidyl choline. Calculated energies of 12 (S) HETE, whether
      complexed to calcium or not, were less favorable than the other HETE compounds.
      CONCLUSIONS: The results of the study indicate that plasma membrane lipids rather
      than Na,K-ATPase itself are more likely to be bound by 12 (R) HETE and its
      related compounds. Moreover, it was found that the calcium complexes of 12 (R)
      HETE and 8 (R) HHDTrE are even more likely to dock with plasma membrane lipids.
      This suggests that such complexes may be able to transport calcium into the cell
      and make it available for the inhibition of Na, K-ATPase at the enzyme's sodium
      binding site.

PMID- 9238093
TI  - Application of a submicroliter spectrophotometer in visual pigment studies.

PMID- 9238094
TI  - Identification of a mutation in the MP19 gene, Lim2, in the cataractous mouse
      mutant To3.
AB  - PURPOSE: Lim2, the gene encoding the second most abundant lens specific integral
      membrane protein, MP19, has recently been proposed as an ideal candidate gene for
      the cataractous mouse mutant, To3. The aim of this study was to screen the Lim2
      gene in the To3 mutant for a genetic lesion that was correlated and consistent
      with the mutant phenotype. METHODS: Genomic DNA was isolated from both normal
      mouse parental strains as well as the heterozygous and homozygous To3 cataract
      mutant. PCR was used to generate overlapping fragments of the entire Lim2 gene
      from these DNAs. The coding regions, including splice junctions and the
      translational termination site, of these fragments were then sequenced. RESULTS:
      A single G -> T transversion was identified within the first coding exon of the
      Lim2 gene in the To3 mutant DNA. This DNA change results in the nonconservative
      substitution of a valine for the normally encoded glycine at amino acid 15 of the
      MP19 polypeptide. CONCLUSIONS: The identified genetic lesion in the Lim2 gene of
      the cataractous mouse mutant, To3, confirms Lim2 as an ideal candidate gene.
      Future transgenic experiments should provide proof or disproof of a causative
      relationship between the identified mutation and the cataractous phenotype. These
      studies indicate that MP19 may play an important role in both normal lens
      development and cataractogenesis, and warrants more intense investigation of its
      role within the ocular lens.

PMID- 9238095
TI  - Neural circuitry and light responses of the dopamine amacrine cell of the turtle
      retina.
AB  - PURPOSE: To understand the circuitry and electrophysiology of the dopamine cells
      in the turtle retina. METHODS: Preembedding immunocytochemistry for tyrosine
      hydroxylase (Toh) was done on vibratome sections of turtle retina. Resultant Toh
      immunoreactive (Toh-IR) amacrine cells were then serially thin-sectioned for
      analysis by electron microscopy (EM). Some sections of Toh-IR cells also were
      post-embedding immunostained for glycine and GABA content. Intracellular
      recordings and dye markings were made from the turtle eyecup and slice
      preparation to determine the light responses of cells called A28, which have the
      same morphology as Toh-IR amacrine cells. RESULTS: Physiologically A28 cells were
      L-type (luminosity) and gave sustained depolarizing (ON-center) responses to
      light pulses. High intensity light pulses produced immediate transients and long
      depolarizations, lasting beyond the stimulus duration. An after-hyperpolarization
      and an antagonistic surround could be elicited. EM reconstruction of a Toh-IR
      cell revealed new circuitry over that described before (Pollard, J. & Eldred,
      W.D. (1990). J. Neurocytol. 19, 53-66). Bipolar ribbon synapses occurred in all
      three dendritic tiers. However, amacrine cell inputs dominated numerically (95%
      amacrine input, 5% bipolar input) many of them in a serial synaptic
      configuration. GABA+ inputs were seen but not glycine+ inputs. Output from Toh-IR
      profiles was primarily to large ganglion cell dendrites but also to bipolar cell
      axons, GABA-IR amacrines, unspecified amacrine cells and other Toh-IR dendrites.
      CONCLUSIONS: The synaptology of the dopamine cells of the turtle retina suggests
      that sustained inhibitory amacrine cell pathways, including GABAergic pathways,
      are chiefly responsible for their response characteristics at low light levels.
      Conversely, at higher light intensities, transient excitatory amacrine cells
      probably have influence.

PMID- 9238096
TI  - Isolation and expression of homeobox genes from the embryonic chicken eye.
AB  - PURPOSE: To identify homeobox-containing genes that may play a role in the
      differentiation of ocular tissues. METHODS: Total RNA was isolated from
      microdissected chicken embryo eye tissues at 3.5 days of development (embryonic
      day 3.5; E3.5). An "anchor-oligo-dT primer" was used for the synthesis of cDNA.
      Degenerate oligonucleotides designed from highly-conserved sequences in the third
      helix of the homeobox and the "anchor-primer" were used to amplify cDNAs by
      polymerase chain reaction (PCR). PCR products were cloned and sequenced. The
      spatial and temporal expression of selected transcripts was mapped by whole-mount
      in situ hybridization and northern blot analysis. RESULTS: After sequencing
      eighteen clones we identified a member of the distal-less family (dlx-3) in cDNA
      from presumptive neural retina and three chicken homologs of the Xenopus
      "anterior neural fold" (Xanf-1) in cDNA from anterior eye tissue. Dlx transcripts
      were mapped by in situ hybridization. Expression began at Hamburger and Hamilton
      stage 14 (E2.5) and was widely distributed in embryonic mesenchyme on E3 and E4.
      Expression increased in the retina during early development and persisted until
      after hatching. The one anf clone selected for further study was not detected by
      in situ or northern blot analysis. CONCLUSIONS: It is feasible to isolate
      homeobox cDNAs directly from microdissected embryonic tissues. Chicken dlx-3 mRNA
      has a wider distribution in the embryo than expected, based on the expression of
      the mouse homolog. Dlx-3 may play a role in establishing or maintaining the
      differentiation of the retina.

PMID- 9238097
TI  - Selenite nuclear cataract: review of the model.
AB  - Selenite overdose cataract, an experimental model of nuclear cataract produced in
      young rats is reviewed. Topics include procedures for cataract production and
      assessment, metabolic and molecular changes in the epithelium of the lens,
      calcium accumulation, activation of calcium-activated protease system, mechanisms
      for crystallin precipitation, anti-cataract drug testing and relevance to human
      cataract.

PMID- 9238098
TI  - Recent advances in genetic analyses of hyperthermophilic archaea and bacteria.
AB  - Hyperthermophilic Archaea and Bacteria are an extraordinarily important class of
      organisms for which genetic tools remain to be developed. Unique technological
      obstacles to this goal are posed by the thermophilic and, in some cases, strictly
      anaerobic nature of these organisms. However, recent advances in the cultivation
      of hyperthermophiles, in the discovery of genetic elements for vector
      development, and in the construction of genetic markers point toward the
      achievement of this goal in the near future. Transformation protocols have
      already been reported for Sulfolobus and Pyrococcus, and plasmid-mediated
      conjugation was recently found in Sulfolobus. Plasmids are available for
      Sulfolobus, Pyrococcus, and the bacterial hyperthermophile Thermotoga, and these
      provide the bases for vector construction in these hosts. A Desulfurococcus
      mobile intron may provide a novel means to introduce genes into a variety of
      archaeal hosts. With full genome sequences of several hyperthermophiles available
      soon, genetic tools will allow full exploitation of this information to study
      these organisms in depth and to utilize their unique properties in
      biotechnological applications.

PMID- 9238100
TI  - Comparative genomic analysis of isolates belonging to the six species of the
      genus Thermus using pulsed-field gel electrophoresis and ribotyping.
AB  - Fifty isolates belonging to the six validly described species of the genus
      Thermus (T. aquaticus, T. filiformis, T. thermophilus, T. scotoductus, T.
      brockianus, and T. oshimai) isolated from hot springs of different geographical
      areas were compared using macrorestriction analysis of genomic DNA and
      ribotyping. With the exception of presumed clones, the macrorestriction patterns
      of isolates obtained with EcoRI or NdeI were distinct. However, isolates
      belonging to the same species exhibited similar profiles particularly when they
      were isolated from the same hot spring. The estimated genomic size of strains of
      the Thermus spp. varied between approximately 1.8 and 2.5 Mbp. Ribotyping with
      BamHI and HindIII produced 30 and 35 distinct ribotypes, respectively. In spite
      of the variability of the hybridization patterns produced, the ribotypes obtained
      for isolates belonging to the same species also shared, in general, several
      fragments of identical size, and these fragments were similar when isolates
      originated from the same spring.

PMID- 9238099
TI  - Biochemical and genetic characterization of the acetaldehyde dehydrogenase
      complex from Acetobacter europaeus.
AB  - The aldehyde dehydrogenase complex, which catalyzes the oxidation of acetaldehyde
      to acetic acid, was purified to apparent homogeneity from the membrane fraction
      of the industrial vinegar-producing strain Acetobacter europaeus. The determined
      Km for acetaldehyde was 2.1 mM. SDS-PAGE of the enzyme complex showed the
      presence of three different subunits with molecular masses of 79, 46, and 17 kDa,
      respectively. The two larger subunits contained heme. The difference spectrum
      indicated a cytochrome c, a heme B, and a [2Fe-2S] cluster. The nucleotide
      sequence of several cloned fragments of a 6-kb chromosomal DNA segment from A.
      europaeus was determined. It contains three consecutive open reading frames that
      correspond to proteins with calculated molecular masses of 84.1, 49.0, and 16.7
      kDa; these were assigned to the purified proteins and named aldH, aldF, and aldG,
      respectively. The N-terminal sequence of the 79-kDa subunit was detected within
      the predicted amino acid sequence of AldH, which indicated the presence of a
      leader peptide. Cotranscription of the three genes was shown by Northern
      hybridization. Sequence analysis and experimental evidence allowed the assignment
      of the following cofactors to the respective subunits of the aldehyde
      dehydrogenase complex: heme C to AldF, [2Fe-2S] cluster to AldG, and heme B and a
      molybdopterin cofactor to AldH. Part of an open reading frame, gdhA, was detected
      upstream of the operon that showed high similarities to the C-terminal part of
      several pyrroloquinoline-chinone-dependent glucose dehydrogenases.

PMID- 9238101
TI  - Identification of stsC, the gene encoding the L-glutamine:scyllo-inosose
      aminotransferase from streptomycin-producing Streptomycetes.
AB  - Eight new genes, strO-stsABCDEFG, were identified by sequencing DNA in the gene
      cluster that encodes proteins for streptomycin production of Streptomyces griseus
      N2-3-11. The StsA (calculated molecular mass 43.5 kDa) and StsC (45.5 kDa)
      proteins - together with another gene product, StrS (39.8 kDa), encoded in
      another operon of the same gene cluster - show significant sequence identity and
      are members of a new class of pyridoxal-phosphate-dependent aminotransferases
      that have been observed mainly in the biosynthetic pathways for secondary
      metabolites. The aminotransferase activity was demonstrated for the first time by
      identification of the overproduced and purified StsC protein as the L
      glutamine:scyllo-inosose aminotransferase, which catalyzes the first amino
      transfer in the biosynthesis of the streptidine subunit of streptomycin. The stsC
      and stsA genes each hybridized specifically to distinct fragments in the genomic
      DNA of most actinomycetes tested that produce diaminocyclitolaminoglycosides. In
      contrast, only stsC, but not stsA, hybridized to the DNA of Streptomyces
      hygroscopicus ssp. glebosus, which produces the monoaminocyclitol antibiotic
      bluensomycin; this suggests that both genes are specifically used in the first
      and second steps of the cyclitol transamination reactions. Sequence comparison
      studies performed with the deduced polypeptides of the genes adjacent to stsC
      suggest that the enzymes encoded by some of these genes [strO (putative
      phosphatase gene), stsB (putative oxidoreductase gene), and stsE (putative
      phosphotransferase gene)] also could be involved in (di-)aminocyclitol synthesis.

PMID- 9238102
TI  - Thermoanaerobacter mathranii sp. nov., an ethanol-producing, extremely
      thermophilic anaerobic bacterium from a hot spring in Iceland.
AB  - The extremely thermophilic ethanol-producing strain A3 was isolated from a hot
      spring in Iceland. The cells were rod-shaped, motile, and had terminal spores;
      cells from the mid-to-late exponential growth phase stained gram-variable but had
      a gram-positive cell wall structure when viewed by transmission electron
      microscopy. Strain A3 used a number of carbohydrates as carbon sources, including
      xylan, but did not utilize microcrystalline cellulose. Fermentation end products
      were ethanol, acetate, lactate, CO2, and H2. The temperature optimum for growth
      was between 70 and 75 degrees C, and growth occurred in the range of 50-75
      degrees C. The pH range for growth was 4.7-8.8, with an optimum at pH 7.0. Strain
      A3 was sensitive to tetracycline, chloramphenicol, penicillin G, neomycin, and
      vancomycin at 100 mg/l but was not sensitive to chloramphenicol and neomycin at
      10 mg/l, which indicates that strain A3 belongs to the eubacteria. Addition of
      50.66 kPa H2 or 2% NaCl did not affect growth. The isolate grew in the presence
      of exogenously added 4% (w/v) ethanol. The G+C ratio was 37 mol%. 16S rDNA
      studies revealed that strain A3 belongs to the genus Thermoanaerobacter.
      Genotypic and phenotypic differences between strain A3 and other related species
      indicate that strain A3 can be assigned to a new species, and the name
      Thermoanaerobacter mathranii is proposed.

PMID- 9238103
TI  - Carbohydrate metabolism in Thermoproteus tenax: in vivo utilization of the non
      phosphorylative Entner-Doudoroff pathway and characterization of its first
      enzyme, glucose dehydrogenase.
AB  - Thermoproteus tenax is a hyperthermophilic, facultative heterotrophic archaeum.
      In this organism the utilization of the two catabolic pathways, a variant of the
      Embden-Meyerhof-Parnas (EMP) pathway and the modified (nonphosphorylative) Entner
      Doudoroff (ED) pathway, was investigated and the first enzyme of the ED pathway,
      glucose dehydrogenase, was characterized. The distribution of the 13C label in
      alanine synthesized by cells grown with [1-13C]glucose indicated that in vivo the
      EMP pathway and the modified ED pathway operate parallel, with glucose
      metabolization via the EMP pathway being prominent. To initiate studies on the
      regulatory mechanisms governing carbon flux via these pathways, the first enzyme
      of the ED pathway, glucose dehydrogenase, was purified to homogeneity and its
      phenotypic properties were characterized. The pyridine-nucleotide-dependent
      enzyme used both NAD+ and NADP+ as cosubstrates, showing a 100-fold higher
      affinity for NADP+. Besides glucose, xylose was used as substrate, but with
      significantly lower affinity. These data suggest that the physiological function
      of the enzyme is the oxidation of glucose by NADP+. A striking feature was the
      influence of NADP+ and NAD+ on the quaternary structure and activity state of the
      enzyme. Without cosubstrate, the enzyme was highly aggregated (mol. mass > 600
      kDa) but inactive, whereas in the presence of the cosubstrate the aggregates
      dissociated into enzymatically active, homomeric dimers with a mol. mass of 84
      kDa (mol. mass of subunits: 41 kDa). The N-terminal amino acid sequence showed
      striking similarity to the respective partial sequences of alcohol dehydrogenases
      and sorbitol dehydrogenases, but no resemblance to the known pyridine-nucleotide
      dependent archaeal and bacterial glucose dehydrogenases.

PMID- 9238104
TI  - Outer membrane proteins of Methylococcus capsulatus (Bath).
AB  - Membranes obtained from whole-cell lysates of Methylococcus capsulatus (Bath)
      were separated by Triton X-100 extraction. The resulting insoluble fraction was
      enriched in outer membranes as assessed by electron microscopy and by the content
      of beta-hydroxy palmitic acid and particulate methane monooxygenase. Major
      proteins with molecular masses of approximately 27, 40, 46, 59, and 66 kDa were
      detected by SDS-PAGE of the Triton-X-100-insoluble membranes. MopA, MopB, MopC,
      MopD, and MopE (Methylococcus outer membrane protein) are proposed to designate
      these proteins. Several of the Mop proteins exhibited heat-modifiable properties
      in SDS-PAGE and were influenced by the presence of 2-mercaptoethanol in the
      sample buffer. The 46- and 59-kDa bands migrated as a single high-molecular-mass
      95-kDa oligomer under mild denaturing conditions. When reconstituted into black
      lipid membranes, this oligomer was shown to serve as a channel with an estimated
      single-channel conductance of 1.4 nS in 1 M KCl.

PMID- 9238105
TI  - Isolation of O-demethylase, an ether-cleaving enzyme system of the homoacetogenic
      strain MC.
AB  - The O-demethylase of the methylotrophic homoacetogenic bacterium strain MC was
      purified to apparent homogeneity. The enzyme system consisted of four different
      components that were designated A, B, C, and D according to their elution
      sequence from the anionic-exchange chromatography column. All four components
      were essentially required for catalysis of the transfer of the methyl group from
      phenyl methyl ethers to tetrahydrofolate. According to gel filtration and SDS
      PAGE, components A and B were monomers with apparent molecular masses of
      approximately 26 kDa (subunit 25 kDa) and 36 (subunit 41 kDa), respectively;
      component C appeared to be a trimeric protein (195 kDa, subunit 67 kDa); and
      component D was probably a dimer (64 kDa, subunit 30 kDa). Component A contained
      one corrinoid per monomer. In crude extracts, component D appeared to be the rate
      limiting protein for the complete methyl transfer reaction. Additional
      requirements for the reaction were ATP and low-potential reducing equivalents
      supplied by either titanium(III) citrate or H2 plus hydrogenase purified from
      strain MC.

PMID- 9238106
TI  - Isolation of the putP gene of Corynebacterium glutamicum and characterization of
      a low-affinity uptake system for compatible solutes.
AB  - Corynebacterium glutamicum accumulates the compatible solutes proline, glycine
      betaine, and ectoine under conditions of high osmolality. Uptake of proline is
      mediated by both a high-affinity and a low-affinity secondary transport system.
      The low-affinity uptake system also accepts glycine betaine and ectoine as
      substrates. In the present study, the gene encoding the high-affinity proline
      uptake system PutP was isolated by heterologous complementation of Escherichia
      coli mutant strain WG389, which lacks the transport systems BetT, PutP, ProP, and
      ProU and is unable to synthesize proline and glycine betaine. This gene (putP)
      encodes a protein of 524 amino acids that shares identity with the proline
      transport systems PutP of E. coli, Staphylococcus aureus, Salmonella typhimurium,
      Haemophilus influenzae, and Klebsiella pneumoniae. Functional studies of PutP
      synthesized in E. coli mutant strain MKH13, which also lacks the transport
      systems for compatible solutes and is unable to synthesize glycine betaine,
      revealed that this carrier system is not regulated by the external osmolality on
      the level of activity. Km values of 7.6 mM for proline and 1.3 mM for sodium as
      cotransported ion were determined. Deletion of the putP gene allowed the
      functional characterization of another proline uptake system with low affinity.

PMID- 9238107
TI  - Cell elongation and septation are two mutually exclusive processes in Escherichia
      coli.
AB  - Bacterial rod morphogenesis was studied in synchronously growing cells of
      Escherichia coli C600 during the reshaping process that follows the removal of
      mecillinam, a beta-lactam antibiotic that specifically inhibits lateral wall
      formation of gram-negative rods and causes transition to coccal shape. Removal of
      mecillinam after 30 min of action did not affect the timing of subsequent cell
      division, but removal after 50 min delayed resumption of cell division for
      approximately one generation time. In order to study the interplay between
      lateral wall elongation and septum formation in determining and maintaining the
      bacterial rod shape, we evaluated the effect of re-adding mecillinam or of adding
      aztreonam (a specific inhibitor of septum formation) at various stages of the
      reshaping process. We conclude that mecillinam was active only during the
      reshaping process, while aztreonam was active only later when the cells were
      close to dividing again. These results provide further evidence for our previous
      proposal according to which elongation and septation are two alternating and
      competing events of the cell cycle and are linked to each other to force
      bacterial rods to grow to a given length.

PMID- 9238108
TI  - Sensitivity to pH, product inhibition, and inhibition by NAD+ of 1,3-propanediol
      dehydrogenase purified from Enterobacter agglomerans CNCM 1210.
AB  - Because of its key role in the metabolism of glycerol during fermentation, 1,3
      propanediol dehydrogenase (EC 1.1.1.202) of Enterobacter agglomerans CNCM 1210
      was purified to homogeneity and studied with respect to its sensitivity to pH and
      to nucleotide and 1,3-propanediol concentrations. Enzyme activity was optimal at
      pH 7.8. The enzyme was competitively inhibited by NAD+ (Ki of 0.29 mM), and 1,3
      propanediol exerted a strong inhibitory effect according to a mixed-type
      inhibition with a Ki of 13.7 mM and an a-factor of 9.0. It is proposed that these
      dehydrogenase properties be extended to the dehydrogenases of Citrobacter
      freundii and Klebsiella pneumoniae, which exhibited numerous similar physical
      properties.

PMID- 9238109
TI  - The biotransformation of t-butylacetonitrile and its boron-containing analogue
      trimethylamine-cyanoborane by Brevibacterium R312.
AB  - The ability of the nitrile hydratase/amidase system from Brevibacterium R312 to
      biotransform tert-butylacetonitrile was studied with a view to their utilisation
      in the production of novel amino acids from isostructural compounds.
      Brevibacterium R312 was able to transform nitriles with this structure; however,
      the wide spectrum amidase from this organism was unable to biotransform the
      corresponding amide to the carboxylic acid.

PMID- 9238110
TI  - Burns (Part 2). Tops and flops using cultured epithelial autografts in children.
AB  - The goal of this article is to review the status of cultured epithelial
      autografts in clinical practice with particular focus on the pediatric subset of
      patients. The current indications include massive deep burns (>60 - 70% total
      body surface area), resurfacing-type postburn scar revisions, and skin defect
      coverage following excision of large skin lesions like giant nevi. Although this
      method can be lifesaving for massively burned patients, and although excellent
      functional and cosmetic results may be obtained under ideal circumstances,
      formidable problems continue to exist. Take is inconsistent, cultured grafts are
      extremely susceptible to infection, and skin breakdown during the first months
      post grafting may occur due to mechanical instability of the regenerating skin.
      It may take one more decade of concerted research, jointly performed by
      clinicians and tissue culture technology experts in order to fabricate more skin
      like grafts which are robust, reliable, and less expensive. Then, "cultured skin"
      will conquer the world and benefit countless patients.

PMID- 9238112
TI  - Scar wars: implications of fetal wound healing for the pediatric burn patient.
AB  - Scar formation and fibrosis often cause devastating disabilities in children
      suffering severe burn injury. In contrast to the child, the fetus has the ability
      to heal skin injury without scar formation, and instead with regeneration of
      epithelial and mesenchymal tissues and restoration of normal skin architecture.
      In this paper we review those unique features of the fetus and fetal wound
      healing that may contribute to the scarless repair process. It is hoped that an
      understanding of these remarkable reparative capabilities may lead to the
      development of new wound healing therapies that reduce or prevent scar formation
      and fibrosis in the management of children with burns.

PMID- 9238111
TI  - Cultured epithelial autografts: diving from surgery into matrix biology.
AB  - Cultured epithelial autografts offer an exciting approach to cover extensive skin
      wounds. The main problem of this method is mechanical instability during the
      first weeks after grafting. There is evidence that the shortcomings of
      autografting cultured keratinocytes result from the lack of a mature and
      functional dermo-epidermal junction. This article summarizes the current
      knowledge regarding the de novo formation of the dermo-epidermal junction and the
      dynamics of "take" and stabilization of cultured epithelial autografts. Future
      strategies are discussed of how to improve and accelerate the process conferring
      definitive stabilization of cultured epithelial autografts including the
      potential therapeutic use of transglutaminase as well as cocultivation of a dermo
      epidermal equivalent in order to facilitate a permanent skin replacement.

PMID- 9238113
TI  - The adaptive immune response to major surgery in the neonate.
AB  - The effect of major surgery on components of the adaptive immune response in
      babies has not previously been reported. In a prospective study, eight neonates
      undergoing uncomplicated surgery for repair of esophageal atresia were
      investigated. They were compared with ten age-matched normal babies not
      undergoing surgery. The parameters of the immune response investigated were:
      total leukocytes (WBC), lymphocytes and their subsets (T-helper, T-suppressor,
      natural killer [NK], B-lymphocytes), monocytes, immunoglobulins (Ig) G and M, the
      cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (Il
      1beta), and C-reactive protein (CRP), an acute-phase protein. When compared to
      the normal controls, the operated group showed a fall in all types of WBC
      following surgery, but only the falls in B-lymphocytes and NK cells were
      significant on postoperative day 3 (P < 0.05). The suppression in WBC was
      temporary, and by day 7 the operated group had significantly higher numbers of
      total WBC and T-helper cells than the controls (P < 0.05), who were undergoing
      their physiological postpartum fall in WBC. Within the operated group, there was
      a significant fall in the numbers of total lymphocytes, T-suppressors, and B
      lymphocytes compared to preoperative levels (P < 0.01). The ratio of T-helper/T
      suppressor cells increased significantly following surgery. There was a vigorous
      immune response in terms of the humoral factors: CRP, TNF-alpha, and Il-1beta all
      rose significantly postoperatively (P < 0.02).

PMID- 9238114
TI  - The non-refluxing gastrostomy: an evaluation.
AB  - A gastrostomy is often essential to deliver adequate and safe nutrition. Various
      types are now available such that the technique can be tailored to the specific
      needs of the patient. This paper explores the non-refluxing gastrostomy for long
      term intermittent gastrostomy feeding, avoiding the need for a permanent
      indwelling appliance. A full-thickness vascularized flap based on the right
      gastroepiploic vessels is raised from the greater curve of the stomach. The
      proximal half of the tubularized flap is buried in a submucosal tunnel and the
      free distal end is brought to the skin surface as a catheterizable stoma. Fifteen
      children with varied mental and physical disabilities formed the cohort of the
      study. There were 3 stomal stenoses and 3 mild mucosal eversions requiring minor
      surgical adjustments. One child had a wound dehiscence 10 days postoperatively.
      Once the stoma had healed, the majority fed by intermittent catheterization and
      bolus feeds at conventional feed times during the day. Intermittent
      catheterization was painless and easy and was well accepted by caregivers and
      patients. Perhaps the most important advantages were the increased patient and
      caregiver confidence and independence, as well as the reduction in anxiety and
      hospital attendance.

PMID- 9238115
TI  - Idiopathic focal foveolar hyperplasia in infants.
AB  - Idiopathic focal foveolar hyperplasia (FFH) is a rare cause of gastric outlet
      obstruction in infants. We present two cases, including the first reported
      association with infantile hypertrophic pyloric stenosis. The diagnostic
      ultrasound appearance of FFH is described. Optimal treatment is surgical excision
      of the involved mucosa with pyloroplasty or pyloromyotomy.

PMID- 9238117
TI  - The efficacy of diagnostic laparoscopic ultrasound.
AB  - Precise staging of malignant disease is required to define the optimum
      therapeutic strategy. In spite of technical advances, the sensitivity of
      conventional imaging techniques is usually limited to defining lesions of at
      least 1 cm in size. Laparoscopy is a sensitive technique that is very valuable
      for visual inspection of the abdominal cavity and the identification of small
      surface lesions. However, non-superficial lesions may escape detection due to the
      lack of tactile sensitivity. As an adjunct to laparoscopy, this study, utilizing
      a young swine model, has analyzed the detectability of intra-abdominal lymph
      nodes by laparoscopic ultrasound (LU). Lymph nodes in and around the
      hepatoduodenal ligament, examined and measured by LU, were resected by subsequent
      open laparotomy in eight young, mixed-breed swine. The numbers and sizes of lymph
      nodes detected by LU and resected at laparotomy were compared and analyzed
      statistically. Forty-six lymph nodes were resected by laparotomy, while LU failed
      to detect 3 small nodes (sensitivity, 43/46 = 93.5%). The sizes of lymph nodes in
      the LU group correlated strongly with the sizes actually measured in the
      laparotomy group (r = 0.936, P < 0.001). Twenty-six small lymph nodes, which
      conventional extracorporeal imaging might have failed to diagnose, were detected
      accurately by LU (r = 0.877, P < 0.001). This new technology may not only be
      effective for staging intra-abdominal malignant disease, but adds the benefit of
      obtaining tissue samples under direct vision using minimally invasive techniques.

PMID- 9238116
TI  - Laparoscopic gastrostomy in children.
AB  - During a 30-month period, 28 children aged 6 months-15 years underwent fashioning
      of a laparoscopic gastrostomy. Indications for operation included: feeding
      difficulties and failure to thrive in neurologically impaired children (13);
      chronic renal failure (9); and others (6). There were 17 conventional tube and 11
      button gastrostomies. Twelve children had insertion of a gastrostomy alone; the
      others underwent a concomitant laparoscopic Nissen fundoplication (NFP). The
      average operation time for gastrostomy alone was 65 min (range 35-104) and for
      gastrostomy plus NFP 155 min (range 130-246). There were no specific laparoscopic
      complications. Two patients who required large volumes of eternal drugs and
      peritoneal dialysis from the 1st post-operative day developed minor external
      leaks from their stomas. It appears that laparoscopy provides for safe and
      precise positioning of any standard balloon or button gastrostomy. It is a
      particularly attractive technique for use in patients already undergoing a
      laparoscopic fundoplication and those in whom other minimally invasive techniques
      are contraindicated or fail.

PMID- 9238118
TI  - Pediatric laparoscopic splenectomy: are there real advantages in comparison with
      the traditional open approach?
AB  - The hospital records of patients who underwent splenectomy during the last 2
      years were reviewed to compare the advantages of the laparoscopic approach with
      traditional open splenectomy (OS). Between March 1994 and March 1996, 16 children
      underwent splenectomy, in 8 using an open approach and 8 by a laparoscopic
      procedure. Of the patients who underwent laparoscopic splenectomy (LS), 2 had a
      concomitant cholecystectomy. Ages ranged between 4 and 11 years (mean 6.4 years);
      there were 9 girls and 7 boys. The indications for splenectomy were: hereditary
      spherocytosis (7 cases); idiopathic thrombocytopenic purpura (4); sickle-cell
      disease (3); and beta-thalassemia (2). The average operating time for OS was 100
      min (range, 50-155), for LS 170 min (range 125-240). The hospital stay for
      patients who had OS ranged from 3 to 9 days (mean 4.7), for those who had LS from
      2 to 5 days (mean 3). One OS patient developed a wound infection. In 3 of the LS
      patients, the spleen was removed via a 7-cm Pfannenstiel minilaparotomy in the
      suprapubic region; in 5 cases the spleen was captured into an extraction bag,
      crushed, and removed through the umbilical orifice. The authors believe that LS
      must be performed only when it is possible to use the extraction bag to remove
      the spleen from the umbilical orifice (spleens weighing less than 700 g) and when
      a concomitant procedure such as cholecystectomy is indicated; in other cases OS
      is preferable.

PMID- 9238119
TI  - Outcome of congenital adrenal hyperplasia.
AB  - In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency,
      affected girls are born with ambiguous genitalia due to increased secretion of
      androgens in utero by the defective adrenal gland. Even though it is generally
      accepted that there are differences between male and female brain development,
      determining factors have been difficult to identify. Girls with CAH have
      frequently been studied to evaluate the impact of prenatal androgen exposure on
      psychological, psychosocial, and psychosexual development, and impairments in
      various areas have been identified. However, there is no comprehensive study
      available regarding the outcome of this chronic disorder in adult life. We
      studied the quality of life in women with CAH, with particular emphasis on how
      they cope with genital malformations, genital operations, and chronic disease as
      well as lifelong medication. The patients filled out questionnaires covering
      their physical state, psychological well-being, social relationships, and
      functional capacity, as well as questionnaires on psychosexual identification and
      psychosocial integration. The results were evaluated using a computerized
      statistical program for social studies. Out of a total of 94 patients above 18
      years of age, 45 agreed to participate and were compared to 46 healthy, age
      matched controls. Age at diagnosis was 2. 31 +/- 1.55 years and 38% suffered from
      the simple-virilizing, 45% from the salt-wasting, and 17.0% from the late-onset
      form of CAH. About one-third of patients had Prader stage 3 or 4 genital
      virilization. While the overall quality of life did not differ significantly, CAH
      patients were more often single (47.8% vs. 66.7%) and fewer of them had children
      (22.2% vs. 38.6%) compared to controls. Significant impairments were found in
      regard to body image and attitudes toward sexuality, but there was no increased
      homosexual preference. The women were successful in adjusting to illness and
      receiving social support. It is speculated that improved psychosocial adaptation
      is part of a coping mechanism that helps to maintain a high level of well-being
      despite impairment. Coping mechanisms should be identified and strengthened in
      order to help patients cope with their chronic illness.

PMID- 9238120
TI  - Anorectal anomalies: anorectal manometric function and anal endosonography in
      relation to functional outcome.
AB  - To assess the relation between continence and the manometric and endosonographic
      state of the anorectal segment after surgery for anorectal anomalies (ARA), 33
      adolescents operated upon for ARA and 14 controls were examined. Seventeen
      patients had low and 16 intermediate or high ARA. Fecal continence was recorded,
      and anal canal manometry was performed by microtransducer. The sphincter muscle
      complex and its relation to the anal opening was visualized by anal
      endosonography (ES). Ten patients had perfect continence, 10 had staining, and 13
      had soiling. The anal canal resting and squeeze pressures were significantly
      different in all three groups, and continence function was significantly
      correlated to anal canal pressures. By anal ES, the internal (IAS) and the
      external anal sphincters (EAS) were identified with various amounts of scar
      tissue in all patients. In patients with high or intermediate anomalies the IAS
      was missing in the lower part of the anal canal, and abundant scar tissue was
      identified in the EAS in all patients. In patients with good continence function,
      the EAS was better preserved than in patients with major incontinence. The
      position of the anus in the EAS muscle complex was assessed, and varying degrees
      of eccentrically placed anal canals were identified. Continence function after
      surgery for ARA is thus correlated to anal canal pressures and ES images. ES,
      which is painless and suitable for use in children, is a valuable tool for
      assessing perianal structures, and the findings may serve as a helpful guide for
      corrective surgery.

PMID- 9238121
TI  - Femoral hernia in childhood: review of 38 cases.
AB  - Femoral hernias rarely occur at any age, but are extremely rare in infancy. We
      present 38 cases of femoral hernia treated in our pediatric surgery department
      during the last 15 years. The number of patients who underwent surgery was high
      compared with other series reviewed. This might be due to the fact that these
      hernias were considered in the differential diagnosis of inguinal pathology in
      childhood. The preoperative diagnosis was correct in 22 cases (57. 8%). After
      surgical treatment no recurrence was reported.

PMID- 9238122
TI  - Laparoscopic orchidopexy for persistent mullerian duct syndrome.
AB  - Persistent mullerian duct syndrome, characterized by the presence of a uterus and
      fallopian tubes in a phenotypic male, frequently presents as undescended testis,
      either intra-abdominal or within a hernial sac. We report the first two
      postpubertal cases successfully managed by a one-stage laparoscopic-assisted
      orchidopexy. The first had one and the second had two intra-abdominal testes. All
      testes were brought to the scrotum after dividing the spermatic vessels while the
      collateral circulation was carefully preserved. The two cardinal therapeutic
      goals, intrascrotal placement of well-vascularized testes and normal hormonal
      function, were achieved. Laparoscopic surgical techniques for this condition are
      discussed.

PMID- 9238123
TI  - Efficacy of bleomycin treatment for symptomatic hemangiomas in children.
AB  - Five children aged 5-19 years had pain in massive, inoperable hemangiomas. They
      were treated with intralesional injections of 2 mg bleomycin as a 0.4 mg/ml
      solution in the painful area. The injections were repeated after 4 -6 weeks for a
      total of 6 -10 times. All children were relieved of pain, and the swelling was
      reduced in all cases. There were no complications or side effects. Bleomycin
      therapy of painful, massive hemangiomas can be recommended in older children.

PMID- 9238124
TI  - Infradiaphragmatic extralobar pulmonary sequestration masquerading as an intra
      abdominal, suprarenal mass.
AB  - Three infants were found to have infradiaphragmatic masses by prenatal
      ultrasound. Postnatal imaging studies confirmed the presence of these masses,
      which were suspected of being intra-abdominal malignancies (neuroblastoma). The
      other principal differential diagnosis was extralobar pulmonary sequestration
      (EPS). Intraoperative findings were consistent with EPS, which was confirmed by
      histologic examination. We present these three infants, review the literature,
      and discuss the evaluation and treatment of infradiaphragmatic EPS.

PMID- 9238125
TI  - Juxta-adrenal malignant schwannoma.
AB  - A case of malignant schwannoma occurring in an 11-year-old boy is described. To
      our knowledge, this is the third case of malignant juxta-adrenal schwannoma
      reported in the literature. It was misdiagnosed at the onset of the disease as a
      post-traumatic renal hematoma. Angiography revealed that the tumor derived its
      blood supply from collateral vessels of the aorta, splenic, and left gastric
      arteries. An analysis of the diagnosis, clinical course, and prognostic factors
      of this rare tumor is performed.

PMID- 9238126
TI  - Xanthogranulomatous pyelonephritis mimicking malignant disease: is preservation
      of the kidney possible?
AB  - Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of pyelonephritis
      rarely seen in children. It is characterized by destruction of the renal
      parenchyma and invasion of adjacent tissues, mimicking renal tumors. Preoperative
      diagnosis is very difficult. Two children with XGP are presented. One underwent
      nephrectomy and the other drainage of a renal abscess with kidney preservation.
      Although surgery is considered the only effective treatment, a high index of
      suspicion and renal biopsy may prevent radical nephrectomy.

PMID- 9238127
TI  - Necrotizing fasciitis and myonecrosis in early childhood: a report of three
      patients.
AB  - Necrotizing fasciitis (NF) is a rare and life-threatening disease. It usually
      presents as a postoperative complication, but rarely appears following trauma or
      without apparent cause. Over a period of 2 years we have treated three infants
      with NF, aged 15, 5, and 30 months, respectively. Two patients developed this
      complication following minor trauma while the third was post-elective bilateral
      inguinal hernia repair. The micro-organisms isolated were Staphylococcus aureus
      with Enterococcus durans in one patient, beta-hemolytic streptococcus in a
      second, and Staph. aureus in the third. The cornerstone of therapy is prompt,
      early, aggressive surgical debridement of the massive necrotic tissue and
      repeated debridement if necessary, with appropriate parenteral antibiotic therapy
      and hyperalimentation. All three patients survived. Early recognition of this
      life-threatening situation is mandatory in achieving survival.

PMID- 9238128
TI  - Vertebral osteomyelitis in an infant presenting with a posterior mediastinal
      mass.
AB  - A rare case of vertebral osteomyelitis and paravertebral abscess that presented
      as a posterior mediastinal tumour with airway compression in a 7-week-old baby is
      presented. The differential diagnosis and the recommended treatment are
      discussed.

PMID- 9238130
TI  - Joint meeting of the British Oncological Association, Association of Cancer
      Physicians, and Royal College of Radiologists. United Kingdom, 5-8 July 1997.
      Abstracts.

PMID- 9238129
TI  - Perianal fetal rhabdomyoma: case report.
AB  - A 4-week-old female was referred with a firm, enlarging perianal mass present
      since birth. At surgery, the lesion appeared to be arising from the subcutaneous
      external sphincter. Local excision was successful with preservation of the
      external sphincter. Histologic examination showed a mixture of undifferentiated
      spindle cells as well as immature and maturing myofibers consistent with a fetal
      rhabdomyoma. This report represents the second case of a fetal rhabdomyoma
      arising in the perianal location. All pediatric cases of fetal rhabdomyoma in the
      literature are reviewed.

PMID- 9238131
TI  - Elderly, poor at risk for costly dental illnesses.

PMID- 9238132
TI  - Don't abandon AIDS prevention, warns WHO.

PMID- 9238133
TI  - Tobacco and health care.

PMID- 9238134
TI  - Tobacco and health care.

PMID- 9238135
TI  - Physician fees: tale of 2 countries.

PMID- 9238136
TI  - Can we finally change the system?

PMID- 9238137
TI  - Can we finally change the system?

PMID- 9238138
TI  - Can we finally change the system?

PMID- 9238139
TI  - Can we finally change the system?

PMID- 9238140
TI  - Can we finally change the system?

PMID- 9238141
TI  - Furious about the forum.

PMID- 9238142
TI  - Understanding and enhancing compliance with the second dose of hepatitis B
      vaccine: a cohort analysis and a randomized controlled trial.
AB  - OBJECTIVE: To determine the predictors and extent of noncompliance with a second
      dose of hepatitis B vaccine and the effectiveness of a compliance enhancement
      strategy. DESIGN: Cohort analysis and randomized clinical trial. SUBJECTS: A
      total of 256 consecutive adults attending a sexually transmitted diseases clinic
      from October 1992 to July 1993 who were seronegative for hepatitis B virus and
      agreed to receive hepatitis B vaccination. SETTING: Hamilton, Ont. INTERVENTION:
      Subjects were followed up for 4 months. Those who did not return for the second
      dose of vaccine by 6 weeks after the first (2 weeks overdue) were randomly
      assigned to the enhanced intervention group (telephone and mail reminders) or the
      regular intervention group (mail reminder only). Subjects were considered
      noncompliant if they did not return for the second dose by 4 months after the
      first. RESULTS: The risk of not returning for the second dose of vaccine within 4
      months after the first was strongly and linearly associated with level of
      education (p = 0.004). The noncompliance rate among those with less than a grade
      10 education was 50%, grade 10-13 education 34%, some college education 15% and
      some university education 9%. In the randomized controlled trial the enhanced
      intervention group had twice the compliance rate of the regular intervention
      group (48% v. 25%; p = 0.008). Subjects with no postsecondary education were
      highly responsive to the enhanced intervention (relative risk 2.1; p = 0.02)
      compared with those with a higher level of education (relative risk 1.0; p =
      1.0). CONCLUSION: Hepatitis B vaccine recipients with lower educational levels
      are at increased risk of noncompliance with the second dose of vaccine but are
      highly responsive to telephone reminders.

PMID- 9238143
TI  - A Canadian hospital-based HIV/hepatitis C look-back notification program.
AB  - OBJECTIVE: To describe the process used to notify pediatric patients who received
      transfusions of blood or blood products at our institution before donor blood was
      routinely screened for antibodies to HIV (1985) and hepatitis C virus (1990), and
      to evaluate the effectiveness of the notification program. DESIGN: Patients who
      had received transfusions were identified through the hospital's medical records
      and the records from the Transfusion Medicine Laboratory. Patients were contacted
      by registered mail to provide notification of transfusion. A questionnaire was
      included with the notification to obtain information about the patient's
      awareness of the transfusion and whether he or she had undergone or planned to
      undergo testing for HIV and hepatitis C virus. SETTING: Tertiary care university
      affiliated teaching hospital in Hamilton, Ont. PATIENTS: Patients 16 years of age
      or younger who had received blood products between February 1978 and November
      1985. Patients who had received only albumin or immune serum globulin were not
      included as these products were not associated with viral transmission in Canada.
      RESULTS: Notification letters were sent to 1546 patients. Of these letters 522
      (33.8%) were returned undelivered. Of the 1024 patients contacted 493 (48.1%)
      responded to the questionnaire, of whom 157 (31.8%) were not aware of their
      transfusion. A total of 130 (26.4%) of the respondents had already undergone
      testing for HIV, and 342 (69.4%) indicated that they would undergo such testing
      as a result of the notification. In contrast, only 30 (6.3%) of 474 respondents
      had undergone testing for hepatitis C virus, but 425 (89.7%) indicated that they
      would undergo such testing. Overall, the patients' response to the notification
      was neutral or positive; however, a number of patients expressed dissatisfaction
      and anxiety. CONCLUSIONS: The high proportion of patients who were unaware that
      they had undergone transfusion and who decided to undergo testing for HIV and
      hepatitis C virus as a result of notification supports the use of notification
      programs such as this one.

PMID- 9238144
TI  - Look-back notification: how do we assess effectiveness?

PMID- 9238145
TI  - Decisions about organ donation should rest with potential donors, not next of
      kin.

PMID- 9238146
TI  - Bioethics for clinicians: 13. Resource allocation.
AB  - Questions of resource allocation can pose practical and ethical dilemmas for
      clinicians. In the Aristotelian conception of distributive justice, the unequal
      allocation of a scarce resource may be justified by morally relevant factors such
      as need or likelihood of benefit. Even using these criteria, it can be difficult
      to reconcile completing claims to determine which patients should be given
      priority. To what extent the physician's fiduciary duty toward a patient should
      supersede the interests of other patients and society as a whole is also a matter
      of controversy. Although the courts have been reluctant to become involved in
      allocation decisions in health care, they expect physicians to show allegiance to
      their patients regardless of budgetary concerns. The allocation of resources on
      the basis of clinically irrelevant factors such as religion or sexual orientation
      is prohibited. Clear, fair and publicly acceptable institutional and professional
      policies can help to ensure that resource allocation decisions are transparent
      and defensible.

PMID- 9238147
TI  - Ruling on physician-assisted suicide near top of agenda at US Supreme Court.

PMID- 9238148
TI  - My daughter is dying.

PMID- 9238149
TI  - A place in the shade: reducing the risks of UV exposure.

PMID- 9238150
TI  - Canada's organ shortage is severe and getting worse.

PMID- 9238151
TI  - Hong Kong reverts to Chinese rule but won't introduce China's strict birth
      control policies.

PMID- 9238152
TI  - Growing popularity of complementary medicine leads to national organization for
      MDs.

PMID- 9238153
TI  - Move to "more corporate" health care system may affect hospital donations.

PMID- 9238154
TI  - XVIII International Symposium on Cerebral Blood Flow and Metabolism. Baltimore,
      Maryland, 15-19 June 1997. Abstracts.

PMID- 9238155
TI  - [Hello Dolly, ewe're welcome].

PMID- 9238156
TI  - [Effect of quinine on the multiple drug resistance and intracellular distribution
      of pirarubicin in LR73 tumor cells: a comparative study with verapamil and S9788
      by confocal laser microspectrofluorometry].
AB  - Effectiveness of chemotherapeutic treatment is limited by multidrug resistance
      (MDR) phenomenon mediated by the overexpression of P-glycoprotein 170 termed Pgp
      which serves as an efflux pump removing several types of cytostatic drugs from
      the MDR cells. Several small molecules, frequently lipophilic cations and weak
      bases, are able to reverse in vitro this resistance. Several studies have shown
      that MDR modulators interact with Pgp. However, some molecules do not interact
      with Pgp but are able to completely restore drug sensitivity (e.g., quinine).
      Bennis et al. (1995) have shown recently that in contrast to verapamil and S9788,
      quinine increases nuclear doxorubicin accumulation without modifying its
      intracellular concentration. From this work, the authors concluded that quinine
      has essentially intracellular targets involved in drug distribution (cytoplasm to
      nucleus) from sequestration compartments. Their results have been obtained using
      spectrofluorometry on cell populations and fluorescence microscopy. By using
      confocal laser microspectrofluorometry, we investigated restoration of nuclear
      THP-DOX accumulation and sensitivity by verapamil, S9788 and quinine in 2
      variants of the Chinese hamster ovary cells LR73, selected for resistance to
      doxorubicin (LR73D) and transfected with the mdr1 gene (LR73R), as well as in the
      sensitive ones (LR73S). Results show that verapamil and S9788 were able to
      restore THP-DOX sensitivity in resistant cells by increasing nuclear THP-DOX
      accumulation. This restoration is the consequence of Pgp inhibition and
      redistribution of the anticancer drug from the cytoplasm to nucleus. Quinine, in
      contrast, restores the sensitivity of MDR cells to THP-DOX and decreased their
      resistance index, but has no effect on THP-DOX nuclear accumulation. This
      suggests that quinine modifies the molecular environment of anthracyclines and/or
      their binding to cytoplasmic targets involved in another mechanism of
      anthracycline action.

PMID- 9238157
TI  - [Subcutaneous administration of interleukin-2 in ambulatory treatment of patients
      with metastatic renal cancer. Three-year results of the SCAPP I program].
AB  - We report a french experience of subcutaneous administration of interleukin-2 in
      treatment of patients with metastatic renal cell carcinoma. Thirty-nine patients
      with metastatic renal cell carcinoma were included in the study. During the 10
      week induction period, interleukin-2 was administrated subcutaneously 5 days a
      week for 8 weeks. The weekly dosage were 90 MIU during weeks 1 and 6; 63 MIU
      during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with
      stable disease received maintenance treatment which was discontinued upon the
      appearance of disease progression or unacceptable toxicity. During the
      maintenance period, interleukin-2 was administered 5 days a week for 4 weeks
      followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63
      MIU in weeks 2 to 4. After completion of induction treatment, 7 of 39 evaluable
      patients (18%) had objective responses with 1 complete response. A diminution of
      dose or interruption of treatment occurred with 7 patients because severe
      toxicity. Other systemic side effects in the remaining patients were acceptable.
      Seventeen patients received maintenance treatment. The median follow-up of all
      the patients included was 21 months. The 1, 2 and 3 years survivals were 64%, 33%
      and 22% respectively. This multicentric trial confirms the efficacity of
      subcutaneously-administered interleukin-2 in patients with metastatic renal cell
      carcinoma in terms of both response rate and survival. Unfortunately, increasing
      total doses of administrated interleukin-2 does not seem to increase efficacity
      according to response rate, but is more toxic.

PMID- 9238158
TI  - [Split-course concomitant radiochemotherapy plus surgery vs. surgery alone in
      squamous cell carcinoma of the esophagus. A non-randomized retrospective study of
      184 patients].
AB  - From April 1989 to October 1995, 184 patients with squamous cell carcinomas of
      the esophagus were treated either with surgery alone (112 patients) or with
      preoperative concomitant radiochemotherapy (72 patients) (2 courses of 18.5 Gy in
      5 fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) days 1-5 and
      cisplatinum day 2, separated by a 2-week interval) followed by surgery, and by 4
      more courses of chemotherapy alone for good responders. Twenty-seven of these
      last 72 patients showed histological complete response at surgery (37.5%). There
      was no statistically significant difference in overall survival between the 2
      groups although there were much more T1 patients (small tumors < or = 5 cm in the
      previous TNM classifications) and less T3 patients (evidence of spread beyond the
      esophagus) in the surgery alone group, and nevertheless, median survival was
      better in the combined treatment group (33.6 months versus 21.8 months). However,
      considering tumor size, there was a statistically significant difference in
      median survival in favor of the combined treatment group for all T2 patients (> 5
      cm without evidence of spread beyond the esophagus in the previous TNM
      classification) (48.6 months versus 13.8 months), both for T2N0 and T2N1
      patients, but also for T1N1 patients (< or = 5 cm with nodal involvement). For
      the few T3 patients (evidence of spread beyond the esophagus in the previous TNM
      classification), there was no statistically significant difference between the 2
      groups, but the survival curves seemed to show some advantage in favor of the
      combined treatment group for T3N1 patients. The sex of the patients and the third
      of the esophagus involved by the tumor did not seem to be of any influence on
      survival. On the other hand, patients 70-year-old and older showed a poorer
      survival than other patients. Finally, significantly less patients died with loco
      regional recurrences in the preoperatory radiochemotherapy group (32% versus 48%)
      than in the group treated by surgery alone.

PMID- 9238159
TI  - Evaluation of long-term results of a modified VAB-6 chemotherapy regimen in a
      cohort of good-risk metastatic non seminomatous germ-cell tumors.
AB  - From 1984 to 1988, we conducted at Institut Gustave-Roussy a phase II trial with
      a modified VAB-6 (mVAB-6) chemotherapy regimen in 50 patients with good prognosis
      metastatic non seminomatous germ-cell tumors, including 27 patients (54%) with
      retroperitoneal lymph nodes only. The mVAB-6 combination consisted of vinblastine
      4 mg/m2/day at d1, of actinomycin D1 mg/m2/day at d1, of cyclophosphamide 600
      mg/m2/day at d1, of cisplatin 120 mg/m2/day at d1 and of bleomycin 20 mg/day from
      d1 to d3. Four cycles of mVAB-6 were delivered every 4 weeks. A complete response
      was observed in 46 patients (92%). The other 4 patients achieved a partial
      response with normal serum tumor markers. Forty-two patients (84%) remain
      continuously free of disease. Eight relapses subsequently occurred 3 to 60 months
      after the end of treatment. Overall 45 patients (90%) remain free of disease
      after a median follow-up of 8 years. The long-term clinical toxicity was minimal.
      Three patients developed secondary tumors: 2 contralateral non seminomatous germ
      cell tumors and 1 pancreatic adenocarcinoma. We conclude that the mVAB-6 regimen
      yielded excellent results and minimal long-term toxicity in this group of
      patients with very good-risk metastatic tumors.

PMID- 9238160
TI  - [Cancer of the uterine cervix in young women. A retrospective study of 337
      cases].
AB  - A retrospective study of 337 cases of cervix cancers in women aged 35 years and
      under, treated between 1980-1990 at the Ibn Rochd Oncology Center in Casablanca,
      was analyzed in order to determine the main characteristics of this disease and
      the influence of age on prognosis. The incidence of these cases was stable
      throughout the 11 years study period with a mean of 7.4% of all cervix cancers.
      The rate of early sexual activity in age under 18 years was particularly high,
      with 80%, of which 45.4% before the puberty. The advanced cases were
      predominating (58.2%). Earlier cases were treated with combined radiotherapy and
      surgery and advanced cases with radiotherapy alone. Overall survival rate was 41%
      at 5 years. It was 45.2% for the 31-35 years of age group and 32% for women aged
      30 years and less. The prognosis of these younger women was especially poor in
      tumoral volume more than 3 cm, in advanced cases, in undifferentiated carcinoma
      and in cases of lymph node involvement. The comparative analysis of all
      prognostic factors in function of the age had permitted to show that women aged
      31-35 years old have been a good prognosis, concerning survival at 5 years, in
      regard to women less 30 years.

PMID- 9238162
TI  - Non P-glycoprotein novel proteins involved in human cancer multidrug resistance.
AB  - Multidrug resistance of cancer cells is a serious problem in the treatment of
      tumors and is the leading cause of the frequent failure of chemotherapy. Cancer
      cell chemoresistance is based on the development of several mechanisms among
      which one of the most important concerns the overexpression of membrane proteins
      to remove cytotoxic compounds from the cytoplasm. The leading archetype of these
      proteins is the P-glycoprotein, a member of the ATP-binding cassette (ABC)
      superfamily of transporters, or traffic ATPases. In the recent past years, new
      non P-glycoprotein membrane proteins, several of which being members of the ABC
      superfamily of transporters, and new genes, have been discovered in cancer cells
      with a multiple drug resistance phenotype. In this article, we briefly review
      these newly discovered entities.

PMID- 9238161
TI  - [Burkitt lymphoma in Cameroon children: descriptive and clinico-anatomical
      aspects].
AB  - This retrospective study is armed to indicate the descriptive and pathological
      aspects of children Burkitt lymphoma in Cameroon. It was performed on a 4 year
      period between July 1988 and July 1992. Children from 0 to 15-year-old who were
      hospitalized and who had histologically provern Burkitt lymphoma were included.
      There were 39 patients, that is 27% of all malignant tumors in children during
      this period. Twenty-four were boys and 15 were girls; the median age was 90
      months (+/-46) (range from 3 to 180 months). All children had Plasmodium
      falciparum infection. EBV serology was positive in 18 patients out of 25 (72%),
      14 (36%) had a good nutritional status, the 25 other patients suffered
      malnutrition. Tumor localizations were: maxillary in 29 (74%) patients, abdominal
      in 7 (18%), other in 3 patients. Clinical stages according to Murphy
      classification were: stage I in 6 (15%) patients, II in 3 (8%), III in 20 (51%)
      and IV in 10 (26%). It is concluded from this series that clinical aspects and
      histological pattern in children Burkitt lymphoma in Cameroon are not different
      from what is observed in other endemic areas.

PMID- 9238163
TI  - [Tumoral vascularization: physiopathology and therapeutic prospects].
AB  - The Folkman's hypothesis postulates that tumor or metastase development is
      angiogenesis dependent. Since 1971, several lines of experimental data have
      supported this hypothesis in particular during the past months. A better
      understanding of the functional balance existing between positive and negative
      regulators of endothelial cell proliferation has paved the way to new therapeutic
      prospects.

PMID- 9238164
TI  - [Receptors for factors of the VEGF (Vascular Endothelial Growth Family)].
AB  - Growth factors of the VEGF (vascular endothelial growth factor) family comprises
      4 well characterized members that play a crucial role in the biology of blood
      vessels. They interact with 3 high affinity tyrosine kinase receptors
      (FLT1/VEGFR1, FLK1/KDR/VEGFR2, FLT4/VEGFR3). VEGF/VEGFR interactions have
      essential functions in blood vessel formation during development, specific phases
      of adult life, and in some pathological processes with neo-vascularization such
      as tumor growth.

PMID- 9238165
TI  - [Concomitant radiochemotherapy in invasive bladder tumors].
AB  - The treatment of muscle-invasive bladder tumors currently consists of radical
      cystectomy with lymph node dissection. A combined radio-chemotherapy treatment
      could allow to preserve a functional bladder without greater risk of relapse. We
      present a review of 38 available publications found in the international
      literature concerning this combination treatment. Only 9 publications with
      appropriate analysis were considered, including 552 evaluable patients, 44% of
      whom were suitable for radical cystectomy. Cisplatin is the most often used drug.
      The protocols are variable and generally well tolerated. The median follow-up
      time is 36 months. The immediate complete response rates vary between 48 and 92%
      and the overall survival rate is between 42 and 82%. The survival with bladder
      preservation is between 38 and 75%, while the disease-free survival with bladder
      preservation is between 33 and 53%. 11% of the initially complete responders had
      a superficial recurrence and 30% had distant metastases. There is no proven
      advantage of neoadjuvant polychemotherapy, there is no consensus for the
      therapeutical protocol, the follow-up protocol remains to be defined, and the
      function of the preserved bladder has to be studied. Only a prospective
      randomized trial could precise the role of this experimental technique compared
      to surgery despite the major evident difficulties (ethical and practical) to
      conduct such a trial.

PMID- 9238166
TI  - [New therapeutic strategies and current research in inoperable locally advanced
      non small-cell lung cancers (stage IIIB)].
AB  - Treatment of patients with inoperable locally advanced non small-cell lung cancer
      (NSCLC) remains disappointing with less of 5% of patients alive at 5 years. Both
      initial local control and circumvention of concomitant undetectable metastatic
      chemoresistant cells are the critical targets for the oncologists in charge of
      this disease. Results of a recent meta-analysis including 22 randomized studies
      comparing standard treatment (i.e. radiotherapy) to sequential chemoradiotherapy
      have undoubtabely well defined the role of cisplatine-containing chemotherapy in
      stage IIIB NSCLC, even if the 5 year survival benefit remains modest. However,
      high complete response rates and prolonged overall survival were observed with
      combinations of new promising chemotherapy regimens and new fractionated
      radiation schedules in several phase II studies. These results have to be
      corroborated by prospective randomized trials. Integration of more aggressive and
      more toxic strategies such as radical surgery in these initial inoperable locally
      advanced NSCLC are evaluating. Around these conventional therapies, the stage
      IIIB NSCLC represent a favoured target to elaborate innovative therapeutic
      approaches based on emergence of biotherapies as recombinant cytokines,
      antitumoral vaccine and gene therapy programs. The contribution of these new
      therapeutic options opens new directions in the therapeutic strategy and leads to
      hope a new promising era in the management and outcome of patients with these
      tumors.

PMID- 9238167
TI  - [Non Hodgkin's malignant lymphoma of the uterine cervix. Apropos of a case].
AB  - The authors report a case of a 61-year-old woman presenting a primary cervical
      non Hodgkin's lymphoma, FIGO stage IIIA and Ann Arbor stage IE. The patient was
      successfully treated by combination of multiple drug therapy and pelvic external
      radiation therapy. Twenty-eight months later, the patient is in good general
      health and complete remission.

PMID- 9238168
TI  - [Malignant anorectal melanoma: description of a clinical case and review of the
      literature].
AB  - Malignant ano-rectal melanoma is a rare pathology without characteristic
      symptoms. It is more frequent in females than in males (ratio 2:1) and represents
      3-15% of anal canal tumours. A case of a woman who recently came to us
      complaining of painful defecation, tenesmus and rectal bleeding induced us to
      reconsider the diagnostic and therapeutic implications in ano-rectal melanoma.
      The low incidence of cases reported and the negative 5-year prognosis are due to
      late, often incidental, diagnosis during clinical observation for hemorrhoids,
      rectal polyps or rhagades, together with the aspecificity of the tumour symptoms.
      We hope our case report emphasizes the importance of conducting early diagnosis
      in patients at risk of ano-rectal melanoma.

PMID- 9238169
TI  - [Tribulations of the p16/MTS1/CDKN2 tumor gene suppressor: a continuing saga].
AB  - Since its recent discovery on chromosome 9p21 band, the p16INK4a/MTS1/CDKN2 gene
      has been reported as one of the most frequently impaired tumor suppressor genes
      (ranking second after p53) in a variety of malignancies, including acute
      lymphoblastic leukemias. In fact, the situation is likely to be more complex than
      expected: the gene has a very unusual status in that sense that it encodes two
      structurally unrelated but functionally similar proteins, p16INK4a and p19ARF. In
      this minireview, the present status of the gene is examined.

PMID- 9238170
TI  - [Gene therapy of primary cancers of the liver: hopes and realities].
AB  - Many efforts have been devoted to the development of gene therapy for primary
      liver tumors. This has been hampered by the absence of efficient gene transfer
      vectors for delivering genes into hepatoma cells in vivo. Also it remains to
      determine which type of gene has to be used to achieve complete tumor regression.
      Recent studies have documented improvements obtained using recombinant adenoviral
      vectors carrying the herpes simplex virus thymidine kinase gene as well as the
      ability to specifically target gene expression into the tumor cells by using the
      alpha-fetoprotein gene regulatory sequence. Therefore it seems reasonable to
      expect the development of clinical protocols in the near future.

PMID- 9238171
TI  - [Melanoma: a new interferon is coming ... handle with care!].

PMID- 9238172
TI  - [Control of metastasis: from biological targets to therapeutic approaches].

PMID- 9238173
TI  - [What is/are the function(s) of trefoil peptides?].
AB  - pS2, SP and ITF have been identified in the eighties. These peptides share a
      consensus proteic domain including 3 disulfide bridges leading to a 3 loop
      structure and subsequently to their name of trefoil peptides. While they are
      normally expressed in restricted parts of the gastrointestinal tract, ectopic
      expression is also observed during gastrointestinal ulcerations and in various
      carcinomas. To date, from numerous studies performed in vitro and in vivo, their
      functions in these pathologies begin to be elucidated.

PMID- 9238174
TI  - [New inhibitors of tumor angiogenesis].
AB  - During the past few years, our understanding of the molecular mechanisms of
      angiogenesis has steadily increased. These informations allowed the design of new
      strategies aimed to kill cancer cells by shutting off the blood vessels through
      which they get the oxygen and nutrients they need to grow. Therapies that target
      tumor blood vessels cause the regression of solid tumors in mice. The possibility
      to obtain synergistic effects by combining antiangiogenic and cytotoxic therapy,
      and the therapeutic applications of these studies will be discussed, following a
      meeting on angiogenesis held in Boston on February 10th and 11th 1997.

PMID- 9238175
TI  - [New therapeutic approaches in acute myeloblastic leukemia (AML) and chronic
      myeloid leukemia (CML)].

PMID- 9238176
TI  - [Primary cerebral lymphoma in AIDS. Retrospective study of 20 patients].
AB  - OBJECTIVES: Analyze the epidemiological pattern of primary central nervous system
      lymphoma in AIDS patients together with the clinical expression and course under
      treatment. METHODS: We retrospectively reviewed 20 patients with AIDS-associated
      primary central nervous system lymphoma hospitalized in our unit between April
      1992 and July 1996. Diagnosis was considered probable when an expansive
      intracranial process was associated with CT-scan enhancement and antitoxoplasma
      therapy failure in patients with extraneurological localization. Diagnosis was
      considered to be certain after histological confirmation. RESULTS: Most-patients
      were male (19/20), with a median CD4 cell count of 9/mm3 (range 0-138). Ninety
      percent had AIDS before diagnosis. The presenting symptoms were mental status
      changes (70%), neurologic deficits (55%), fever without another cause (30%),
      increased intracranial pressure (25%) or seizures (25%). Opportunistic diseases
      were usually associated (60%). CT-scan (18/20) showed spontaneous iso or
      hyperdense lesions, most often solitary (67%), with nodular contrast enhancement
      (72%). When performed (7/20), magnetic resonance imaging showed hypointense
      lesions on T1-weighted images with marked contrast enhancement. Diagnosis of
      primary central nervous system lymphoma was suspected in 19 patients because of
      the failure of antitoxoplasma treatment; 4 patients had stereotactic biopsy which
      confirmed the diagnosis. Patients were treated with either total brain radiation
      therapy (10%), corticosteroids (30%), or both (60%). The median survival time
      after onset of symptoms was better with combined therapy or radiation therapy
      alone than with steroids alone (6 vs. 2 months). Interestingly, most of the
      patients died from neurological complications of lymphoma (85%). DISCUSSION: The
      frequency of lymphoma-related death is probably due to better management of
      opportunistic infections and the effect of antiretroviral therapy. Further
      studies combining antiretroviral therapy, radiation and chemotherapy in patients
      with good performance status should be considered to improve the poor prognosis
      of AIDS-associated primary central nervous system lymphoma.

PMID- 9238177
TI  - [Effects of intravenous immunoglobulins in thrombopenia related to septic shock].
AB  - OBJECTIVES: Intravenous immunoglobulins have been shown to be effective in the
      treatment of immunologically mediated thrombocytopenia. Several articles have
      been published on the positive effect of immunoglobulins in sepsis-related death.
      We retrospectively studied the effects of intravenous immunoglobulins used during
      septic shock thrombocytopenia over a 5-year period in a polyvalent intensive care
      unit. PATIENTS AND METHODS: Inclusion criteria were development of acute
      thrombocytopenia under 75 G/l during septic shock, excluding all cases of
      disseminated intravascular coagulation. Thirty-five patients were included in the
      study; 18 were given polyvalent intravenous immunoglobulins (group IgIV) and 17
      were not (controls). The two groups were comparable for SAPS and APACHE II
      gravity scores at admission and at day 0 (first day of septic shock with platelet
      count under 75 G/l), age, sex, platelet count at admission, OSF score, type of
      referral unit, McCabe score, and the presence of 4 parameters which might affect
      platelet count hemofiltration, ARDS, surgery, Swan-Ganz catheter. RESULTS:
      Platelet counts increased on day 8 in the treatment group (63.5 G/l, range 25-453
      versus 105.7 G/l, range 38-355; p = 0.0505). The number of days with
      thrombocytopenia was the same in both groups. Overall mortality was high (60%)
      but there was a difference between the two groups in favor of the treated group
      (74.7% versus 44.4%; p = 0.053). The number of red cell units (214 vs. 164) and
      plasma units (175 vs. 54) transfused was higher in the control group. Platelet
      transfusion was equivalent in the two groups. DISCUSSION: Although we were unable
      to demonstrate a significant difference in the effects of immunoglobulins on
      platelet level and mortality, the trend during this evaluation was comparable
      with that reported in the literature. For transfusion, and although the results
      were not significant, a notion of reduced risk was evident. Prospective trials
      are needed to confirm these observations.

PMID- 9238179
TI  - [Latrodectism: a rare cause of rhabdomyolysis].

PMID- 9238178
TI  - [Multigenic thrombophilia: genetic anomaly of factor II and mutation of factor V
      Leiden. Study in a French family].
AB  - BACKGROUND: A genetic variation of the prothrombin (factor II) gene, a G to A
      transition at nucleotide position 20210, was recently found in patients with
      familial thrombophilia (predisposition to venous thrombosis). It seems to be
      frequent in patients with the factor V Leiden mutation. We report a family with
      the factor V Leiden and/or the genetic variation of prothrombin in 3 members.
      CASE REPORT: The patient had repeated episodes of deep vein thromboses starting
      at the age of 30 during the 4th pregnancy. She is a heterozygous carrier of both
      the factor V Leiden nutation and the prothrombin mutation 20210 A. She has 4
      asymptomatic children, aged 28 to 32 and 3 of them have been explored: one son
      has the prothrombin mutation, one daughter the factor V Leiden and one has none
      of them. DISCUSSION: This case report illustrates the polygenic nature of
      thrombophilia which may explain the heterogeneity of clinical expression observed
      in isolated congenital abnormalities, especially in factor V Leiden mutation.

PMID- 9238180
TI  - [Drug-induced myopathies: an etiology to be evoked].

PMID- 9238181
TI  - [Pseudo-pancreatitis in L. icterohaemorrhagiae leptospirosis].

PMID- 9238182
TI  - [Nuclear medicine in children].
AB  - Pediatric nuclear medicine (PNM) is now well established as a major imaging
      modality in children. Recent technical advances in gamma cameras and associated
      data processing, together with the development of new tracers has modified
      routine practice in PNM. In order to better ascertain how PNM is routinely used
      in France, all nuclear medicine departments in Paris and its suburbs answered a
      detailed questionnaire. The results show three main indications for PNM:
      exploration of the skeleton (33.3%), the urinary tract (23.5%) and the lung
      (22.5%).

PMID- 9238183
TI  - [At the Academie Nationale de Medecine. Prenatal screening of anti-HIV
      antibodies].

PMID- 9238184
TI  - [Treatment of neurogenic pain in adults with cancer. Retrospective study].

PMID- 9238185
TI  - [Kaposi disease].

PMID- 9238186
TI  - [Ultraviolet irradiation devices. Risks related to their use].

PMID- 9238187
TI  - [New treatments of hemoglobinopathies].

PMID- 9238188
TI  - [Intra-lobar bronchopulmonary sequestration].

PMID- 9238189
TI  - Overview of biological themes in PTSD.

PMID- 9238190
TI  - The prevalence and longitudinal course of PTSD. Implications for the
      neurobiological models of PTSD.

PMID- 9238191
TI  - Comorbid psychiatric disorders in PTSD. Implications for research.
AB  - It is clear from the existing data that PTSD often occurs in the context of other
      major psychological conditions. Evidence to support this comes from clinical
      studies, epidemiological studies, and studies of PTSD among substance abusers.
      Clearly, probably several different subgroups of PTSD patients exist including
      those who had psychological or behavioral problems before exposure to traumatic
      events (e.g., substance abuse), those who developed other problems concurrent
      with exposure to the traumatic events, and those who developed problems secondary
      to the development of PTSD, perhaps in efforts to cope with the intensely
      debilitating symptoms of PTSD. With this knowledge, research on PTSD must begin
      to contend with the comorbidity issue in systematic ways. The use of comparison
      groups that are carefully selected is one key way in which conclusions about PTSD
      can be most conservatively drawn. The use of statistical procedures to control
      for difference in levels of comorbidity is another responsible way in which to
      approach the problem. Finally, efforts to employ global measures of functioning
      such as the Global Assessment of Functioning to equate subjects within a study on
      minimally this characteristic may be the most economical method for trying to
      rule out the role of comorbidity and severity of condition in conclusions drawn
      in research studies. All these solutions presuppose the careful measurement of
      comorbidity in studies of PTSD, a recommendation that requires serious
      consideration for researchers operating in this field.

PMID- 9238192
TI  - Familial risk factors in posttraumatic stress disorder.

PMID- 9238193
TI  - Comments on the "empirical basis for biological studies of PTSD".

PMID- 9238194
TI  - Sensitization of the hypothalamic-pituitary-adrenal axis in posttraumatic stress
      disorder.

PMID- 9238196
TI  - Functional neuroimaging studies in posttraumatic stress disorder.

PMID- 9238195
TI  - Structural brain changes in PTSD. Does trauma alter neuroanatomy?
AB  - Although the impetus for studying hippocampal morphology and functioning in PTSD
      was the finding that stress could result in hippocampal damage in rodent and
      primate models, it is far from proven that the findings to date in PTSD represent
      defects that have been caused by trauma. It is equally possible that the findings
      represent a preexisting anomaly which might serve as a risk factor for the
      development of PTSD following trauma exposure. To resolve this dilemma, it is
      necessary to study persons at high risk for trauma (e.g., soldiers) prior to
      trauma exposure and ag in after exposure. Such methods will permit the
      determination not only of whether trauma alters hippocampal morphology, but also,
      if so, of whether this effect is limited to persons with PTSD. At the present
      time, the field would be well advised to proceed vigorously but with appropriate
      caution along these lines of research. As just outlined, sample sizes have been
      small, and potentially confounding variables have abounded in most studies. The
      next few years of research may well continue to replicate the finding of abnormal
      hippocampal morphology in PTSD. However, it would not be surprising to find that
      other brain regions are also involved and that these represent part of a broader
      risk spectrum for the development of psychopathology under stress. Until these
      issues are clarified, the neuroanatomical findings to date in PTSD should be
      viewed as tentative, tantalizing, and in need of additional study.

PMID- 9238197
TI  - The psychobiology of traumatic memory. Clinical implications of neuroimaging
      studies.

PMID- 9238198
TI  - Psychophysiologic reactivity to trauma-related imagery in PTSD. Diagnostic and
      theoretical implications of recent findings.

PMID- 9238200
TI  - Psychobiology of sleep disturbances in posttraumatic stress disorder.
AB  - Sleep disturbances are prominent complaints of PTSD patients. Some, but not all,
      of the polysomnographic studies support the occurrence of sleep disruption. The
      main dimensions of sleep disturbance in the disorder relate to arousal regulation
      and REM-related functions of dreaming and memory processing. Both of these issues
      are relevant to the pathogenesis of PTSD and manifestations of the disorder
      during wake states. Studies elucidating the effects of treatment on sleep
      parameters are an important direction for future research.

PMID- 9238199
TI  - Noradrenergic alterations in posttraumatic stress disorder.

PMID- 9238201
TI  - Psychobiological effects of sexual abuse. A longitudinal study.

PMID- 9238202
TI  - Preliminary evidence for abnormal cortical development in physically and sexually
      abused children using EEG coherence and MRI.

PMID- 9238203
TI  - Issues in the developmental neurobiology of traumatic stress.

PMID- 9238204
TI  - The role of early adverse life events in the etiology of depression and
      posttraumatic stress disorder. Focus on corticotropin-releasing factor.

PMID- 9238205
TI  - Performance of PTSD patients on standard tests of memory. Implications for
      trauma.
AB  - Mental health professionals have employed a variety of clinical and experimental
      neuropsychological tests for exploring purported memory alterations in PTSD.
      Protocols range from standard tests of immediate and delayed learning, recall,
      and recognition to elaborate paradigms using experimental stimuli for assessment
      of information-processing skills. Whereas the former have typically focused on
      general learning and memory capabilities, experimental paradigms have examined
      the role of trauma-related cues and their impact on remembering. Findings to date
      suggest that memory abilities in PTSD patients range from intact to mildly
      impaired on general tests of verbal or visual memory. At the same time, memory
      tests involving trauma-specific stimuli point to alterations in cognitive
      information processing, specifically, an attentional bias manifested by changes
      in speed, accuracy, and depth of processing. The role of a semantic information
      network involving enhanced specificity for trauma cues is discussed along with
      possible implications for brain structures and theories of PTSD.

PMID- 9238206
TI  - Implicit and explicit memory for trauma-related information in PTSD.
AB  - Experiments on content-dependent memory abnormalities in PTSD suggest several
      conclusions. First, PTSD patients exhibit enhanced recall of words related to
      trauma relative to trauma-exposed persons with the disorder. Recognition tests,
      however, appear insensitive to these effects. Second, PTSD patients do not
      exhibit implicit memory biases for trauma cues on implicit memory tasks that are
      strongly influenced by perceptual (e.g., orthographic) aspects of input. They
      may, however, exhibit enhanced implicit memory for trauma-related material on
      conceptually more complex tasks. Third, directed forgetting research suggests
      that adult survivors of childhood sexual abuse who have PTSD exhibit memory
      deficits only for neutral and positive material, not for material related to
      their abuse. Psychiatrically healthy survivors exhibit normal memory performance
      in this paradigm. Fourth, autobiographical memory research indicates that trauma
      survivors, especially those with PTSD, are characterized by difficulties
      retrieving specific memories from their past in response to cue words. These
      findings are especially dramatic in Vietnam combat veterans whose self
      presentational style suggests a fixation to the war and a failure of their
      autobiography to unfold.

PMID- 9238207
TI  - Trauma, dissociation, and memory.

PMID- 9238208
TI  - The neurobiology of emotionally influenced memory. Implications for understanding
      traumatic memory.
AB  - Substantial evidence from animal and human subject studies converges on the view
      that memory for emotionally arousing events is modulated by an endogenous memory
      modulating system consisting, at minimum, of stress hormones and the amygdaloid
      complex. Within the normal range of emotions experienced, this system is viewed
      as an evolutionarily adaptive method of creating memory strength that is, in
      general, proportional to memory importance. In conditions of extreme emotional
      stress, the operation of this normally adaptive system may underly the formation
      of strong, "intrusive" memories characteristic of PTSD. An improved understanding
      of the neurobiology of memory modulation should lead to an improved ability to
      treat or prevent traumatic memories.

PMID- 9238209
TI  - Stress-activated hormonal systems and the regulation of memory storage.

PMID- 9238210
TI  - How the brain processes emotional information.

PMID- 9238211
TI  - Stress effects on morphology and function of the hippocampus.
AB  - The hippocampal formation, which contains high levels of adrenal steroid
      receptors, is vulnerable to insults such as stroke, seizures, and head trauma,
      and it is also sensitive and vulnerable to the effects of stress. We have
      discovered that the hippocampus of rodents and tree shrews shows atrophy of
      pyramidal neurons in the CA3 region. Psychosocial stress and restraint stress
      produce atrophy over approximately 3-4 weeks. Atrophy is blocked by inhibiting
      adrenal steroid formation and by blocking the actions of excitatory amino acids
      using Dilantin or NMDA receptor inhibitors. Glucocorticoid administration also
      blocks CA3 atrophy, but Dilantin administration blocks this as well, indicating
      that excitatory amino acid release mediates the atrophy, which likely involves
      disassembly of the dendritic cytoskeleton. Studies with in vivo microdialysis in
      several laboratories have shown that glutamate release in the hippocampus
      increases in stress and that stress-induced glutamate release is reduced by
      adrenalectomy. Recent electron microscopy of mossy fiber terminals on CA3 neurons
      has revealed a depletion of synaptic vesicles as a result of repeated stress. The
      mossy fiber terminals appear to be responsible for driving atrophy of CA3
      neurons, which involves principally atrophy of the apical dendrites. These
      results are discussed in relation to data from MRI showing atrophy of the whole
      human hippocampus in Cushing's disease, recurrent depressive illness, PTSD, and
      normal aging as well as dementia.

PMID- 9238212
TI  - Kindling versus quenching. Implications for the evolution and treatment of
      posttraumatic stress disorder.

PMID- 9238213
TI  - Stressor-induced oscillation. A possible model of the bidirectional symptoms in
      PTSD.

PMID- 9238215
TI  - Animal models of relevance to PTSD.

PMID- 9238214
TI  - Roles of the amygdala and bed nucleus of the stria terminalis in fear and anxiety
      measured with the acoustic startle reflex. Possible relevance to PTSD.

PMID- 9238216
TI  - The psychobiology of posttraumatic stress disorder: an overview.

PMID- 9238217
TI  - Drug treatment for PTSD. Answers and questions.

PMID- 9238218
TI  - Treatment failure in acute PTSD. Lessons learned about the complexity of the
      disorder.

PMID- 9238219
TI  - Integrating objective indicators of treatment outcome in posttraumatic stress
      disorder.

PMID- 9238220
TI  - Psychological processes related to recovery from a trauma and an effective
      treatment for PTSD.

PMID- 9238221
TI  - PTSD in WWII mustard gas test participants. A preliminary report.

PMID- 9238222
TI  - Relationship between level of spinal cord injury and posttraumatic stress
      disorder symptoms.

PMID- 9238223
TI  - Acute post-rape plasma cortisol, alcohol use, and PTSD symptom profile among
      recent rape victims.

PMID- 9238224
TI  - The acute stress response following motor vehicle accidents and its relation to
      PTSD.

PMID- 9238225
TI  - Salivary cortisol and PTSD symptoms in Persian Gulf War combatants.

PMID- 9238227
TI  - Urinary catecholamine excretion in childhood overanxious and posttraumatic stress
      disorders.

PMID- 9238226
TI  - Behavioral and plasma cortisol responses to sodium lactate infusion in
      posttraumatic stress disorder.

PMID- 9238228
TI  - Psychoendocrinological observations in women with chronic pelvic pain.

PMID- 9238229
TI  - The dexamethasone suppression test and glucocorticoid receptors in borderline
      personality disorder.

PMID- 9238230
TI  - Enduring effects of early abuse on locomotor activity, sleep, and circadian
      rhythms.

PMID- 9238231
TI  - Neurological status of combat veterans and adult survivors of sexual abuse PTSD.
AB  - We found higher levels of positive soft neurological signs in PTSD participants
      than in participants who also experienced similar trauma but did not develop
      PTSD. This finding was replicated in two samples, that is, Vietnam combat
      veterans and adult female survivors of childhood sexual abuse, despite
      differences in gender, age, nature of trauma, and period of life when the trauma
      occurred. Past developmental history of participants and a substance abuse
      history of first-degree relatives also differentiated PTSD from non-PTSD groups
      in both combat and sexual abuse samples. Evidence for neurological impairment and
      compromised developmental history raises the possibility of pretrauma impairment
      as a risk factor for the development of PTSD.

PMID- 9238232
TI  - Source monitoring in PTSD.

PMID- 9238233
TI  - Neuropsychological assessment of Vietnam combat veterans with and without PTSD.

PMID- 9238234
TI  - Abnormal cerebral laterality in posttraumatic stress disorder.

PMID- 9238235
TI  - Startle deficits in women with sexual assault-related PTSD.

PMID- 9238236
TI  - Psychophysiologic assessment of PTSD in adult females sexually abused during
      childhood.

PMID- 9238237
TI  - Interest of events-related potentials in assessment of posttraumatic stress
      disorder.

PMID- 9238238
TI  - Evidence for diminished P3 amplitudes in PTSD.

PMID- 9238239
TI  - Electrophysiology of combat-related PTSD.

PMID- 9238240
TI  - Electrophysiological abnormalities in PTSD.

PMID- 9238241
TI  - MRI reveals gross structural abnormalities in PTSD.

PMID- 9238242
TI  - Reduced hippocampal volume and n-acetyl aspartate in posttraumatic stress
      disorder.

PMID- 9238243
TI  - A positron emission tomographic study of symptom provocation in PTSD.

PMID- 9238244
TI  - VEPs and AEPs: mapping of occlusive lesions in cerebral vessels.

PMID- 9238245
TI  - Posttraumatic stress and depression. A neurochemical anatomy of the learned
      helplessness animal model.

PMID- 9238246
TI  - Psychophysiologic parameters of traumatic stress disorder in rats.
AB  - Nonhabituation of the acoustic startle response is used to identify rat subjects
      with altered alarm responses subsequent to trauma exposure. Subjects (n = 31)
      were exposed to 30 minutes of intermittent tail shock on 2 days followed by
      exposure to the apparatus on the third day. Twenty-nine percent of traumatized
      rats developed nonhabituation of startle over the subsequent 3 weeks of testing.
      No control rats developed nonhabituation of startle reactions over a similar time
      period. These data suggest that this system represents a more accurate
      representation of clinical PTSD than do other animal models.

PMID- 9238247
TI  - Serotonergic modulation of learned helplessness.

PMID- 9238248
TI  - Effects of isolation-rearing on acoustic startle and pre-pulse inhibition in
      Wistar and fawn hooded rats.

PMID- 9238250
TI  - The future of pediatric and adolescent endocrinology.

PMID- 9238249
TI  - Neurobiological alterations in adult nonhuman primates exposed to unpredictable
      early rearing. Relevance to posttraumatic stress disorder.

PMID- 9238251
TI  - Development of the hypothalamic-pituitary-ovarian axis.
AB  - The onset of puberty is a centrally driven process, the detailed mechanisms of
      which are not known. It is translated into an increased activity of the
      hypothalamic GnRH pulse generator. This in turn is seen as increased pituitary
      pulsatile secretion of LH and FSH. LH pulses are observed even in midchildhood,
      particularly after the onset of sleep. Onset of puberty is associated with a
      greater increase in LH pulse amplitude than frequency and a much greater increase
      in LH and FSH. A progressive increase in daytime pulsatility occurs, with a
      gradual reduction of sleep-entrained amplification. Prepubertal FSH
      concentrations are relatively high in girls, and continous ovarian follicular
      growth and atresia take place, with estradiol concentrations being higher than in
      boys. Only after the steep early pubertal increase in LH, ovarian steroidogenesis
      is activated, with increases in androgen and estrogen secretion. Under further
      FSH stimulation, follicular growth and maturation proceed. The first menstrual
      cycles are mostly anovulatory for 1 to 2 years. Luteal phase insufficiency is
      common the first five years after menarche.

PMID- 9238252
TI  - Ovarian aging.

PMID- 9238253
TI  - Autocrine-paracrine role of ovarian corticotropin-releasing hormone.

PMID- 9238255
TI  - Adrenarche.

PMID- 9238256
TI  - Modifications of growth hormone secretion during female puberty.
AB  - Growth hormone levels rise steadily through normal puberty, in parallel with the
      pubertal stages but decline rapidly at the end of puberty (stage V). The general
      evolution of the secretory profile of GH is parallel to the growth velocity
      curve. The frequency of GH pulses remains unchanged; however, their amplitude,
      mean integrated concentrations, area under the curve, and urinary growth hormone
      are elevated at midpuberty. The main action of GH is to ensure, together with sex
      steroids, the pubertal growth spurt. However, the role of pubertal GH is not
      confined to inducing the pubertal growth spurt. It also participates, together
      with sex steroids, in the acquisition of adult bone mineral density.

PMID- 9238254
TI  - The hypothalamic-pituitary-adrenal axis and the female reproductive system.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system
      are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts
      profound, mostly inhibitory effects, on the reproductive axis, with corticotropin
      releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting
      hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and
      ovarian estrogen and progesterone secretion and rendering estrogen-target
      tissues, such as the endometrium, resistant to the gonadal steroid. These effects
      of the HPA axis are responsible for the "hypothalamic" amenorrhea of stress,
      depression and eating disorders, and the hypogonadism of Cushing's syndrome.
      Conversely, estrogen directly stimulates the CRH gene, which may explain the
      slight hypercortisolism of females and the preponderance of depressive, anxiety,
      and eating disorders, as well as Cushing's disease in women. Interestingly,
      several components of the HPA axis and their receptors are present in
      reproductive tissues, as autocoid regulators of their various functions. These
      include ovarian and endometrial CRH, which may participate in the inflammatory
      processes of the ovary, that is, ovulation and luteolysis, and of the
      endometrium, that is, implantation and menstruation. Finally, the
      hypercortisolism of the latter half of pregnancy can be explained by high levels
      of placenta CRH in plasma. This hypercortisolism causes a transient adrenal
      suppression in the postpartum period, which may explain the postpartum
      blues/depression and autoimmune phenomena of this period.

PMID- 9238257
TI  - Neuromodulatory role of opioidergic system on hypothalamus-pituitary-gonadal axis
      during puberty.

PMID- 9238258
TI  - The relationship between the immune and endocrine systems.
AB  - Increasing evidence links the immune and endocrine systems. Cytokines produced by
      activated immune and immune accessory cells can affect, positively or negatively,
      the secretion of hormones from the hypothalamic-pituitary-adrenal or hypothalamic
      pituitary-ovarian axes. On the other hand, adrenal and ovarian hormones affect
      the secretion of cytokines by cells of the immune system. The interaction also
      occurs at a local level in paracrine or autocrine fashion. Cytokines produced by
      resident ovarian macrophages or ovarian cells can affect the follicle and the
      corpus luteum and, consequently, ovarian steroidogenesis at both phases of the
      menstrual cycle. Conversely, the ovarian steroids influence, positively or
      negatively, the secretion of cytokines from both the resident macrophages and
      local endocrine cells.

PMID- 9238259
TI  - Depression and suicide in children and adolescents.
AB  - Presented here is a review of data regarding depression and suicide in children
      and adolescents. It covers prevalence, developmental vulnerabilities, defenses
      specific to adolescence, and symptoms specific to this transitional age.
      Psychosomatics, family relations, and societal and moral stresses as they affect
      psychic stability and identity formation are discussed. Precipitation factors,
      suicide risk assessment, and review of treatment interventions are included.

PMID- 9238260
TI  - Estrogen and progesterone receptors in the endometrium.
AB  - The endometrium, as a target of estrogens and progestins, possesses the
      respective receptor proteins. These receptors belong to the superfamily of
      nuclear receptors, having important functional domains required for steroid
      ligand binding, for dimer formation, for interaction with HREs of DNA, for
      transcription modulation, for association with other proteins, for intracellular
      trafficking, and other activities. The mechanism of action of the steroid
      hormones involves modulation of gene activity through interaction of the hormone
      receptor complex with HREs and with other nuclear proteins, but also encompasses
      nongenomic effects, which accounts for the rapid effects of the steroids on
      cellular functions. Antihormones-antiestrogen and antiprogestins-compete with
      their respective hormones for binding sites on the receptor molecules. Some
      antihormones are partial agonists. The molecular mechanisms underlying the dual
      behavior of antihormones is under consideration. The concentration of ER and PR
      in different physiological and pathophysiological states, such as the menstrual
      cycle, pregnancy, and endometrial cancer, has been determined by biochemical and
      immuno(cyto)chemical methods. The levels of estrogens and progestins are
      important regulators of ER and PR gene expression. Estradiol acts as a cell
      mitogen, inducing key genes involved in replication, and its tumor promoter
      effect is discussed in this sense, whereas progesterone has reverse effects when
      compared to estradiol and acts as a differentiation factor. The cross-talk
      between the endocrine system, growth factors, and neurotransmitters can take
      place both at the receptor level, involving mainly phosphorylation reactions, and
      at the gene level, mainly through protein-protein interactions.

PMID- 9238261
TI  - Endometrial corticotropin-releasing hormone: expression, regulation, and
      potential physiological implications.
AB  - Our findings show that human and rat uterus express the CRH gene. Epithelial
      cells of both species are the main source of endometrial CRH, while stroma does
      not seem to express it, unless it differentiates to decidua. Immunoreactive CRH,
      produced by endometrial cells, has the chromatographic characteristics of
      authentic hypothalamic CRH, while the size of its mRNA in both human and rat
      uterus is similar to or identical with its counterpart, present in placenta and
      hypothalamus (1.3 kb). Estrogens and glucocorticoids inhibit and prostaglandin E2
      stimulates the promoter of human CRH gene in transfected human endometrial cells,
      suggesting that endometrial CRH gene expression is under the control of these
      agents. Moreover, in rats, endometrial CRH expression is significantly higher at
      implantation sites, compared to that at interimplantation uterine regions. Given
      the proinflammatory/vasoregulatory properties of CRH, we hypothesize that
      endometrial CRH may participate in the regulation of intrauterine phenomena, such
      as blastocyst implantation, endometrial vascularization, and myometrial
      contractility.

PMID- 9238262
TI  - Uterine pinopodes in peri-implantation human endometrium. Clinical relevance.
AB  - Current clinical studies indicate the existence in the human of an
      "implantation/nidation window," similar to that observed in animal models. During
      this short period of uterine receptivity, the formation of pinopodes on the
      apical cell membrane of the endometrial epithelium is a consistent morphological
      event, observed in a number of species studies including the human. In order to
      develop a specific marker of the implantation window in clinical practice, we
      have investigated the kinetics of pinopode formation through sequential
      endometrial sampling under various hormonal conditions. Our results show that the
      implantation window in humans, according to this marker, lasts less than 48
      hours, and the timing of its opening is dependent on the hormonal treatment
      applied, occurring earlier in cycles following ovarian stimulation and later in
      cycles induced by hormone replacement treatment. Furthermore, the timing varies
      among different individuals under the same treatment. These findings suggest that
      examination for pinopodes in endometrial samples can be highly useful in
      infertility treatment and research for the assessment of the nidation window on
      an individual basis. Our preliminary data strongly support the value of this
      assessment for better timing of ovum transfer, leading to an increase in
      implantation rates. Studies are now in progress on the expression of other
      endometrial signals present in relation to the pinopodes.

PMID- 9238263
TI  - Neuroendocrinology of the menstrual cycle.

PMID- 9238264
TI  - Luteal function--luteolysis.

PMID- 9238265
TI  - Dysfunctional uterine bleeding.
AB  - Dysfunctional uterine bleeding (DUB) is a frequent gynecological problem during
      adolescence and the most frequent cause of urgent admission to the hospital over
      this period of life. In about 95% of cases it is caused by the late maturation of
      the hypothalamic-pituitary-ovarian axis (HPO), leading to anovulatory cycles.
      These adolescents lack the E2 positive feedback on LH. Thus, the continuous
      production of estrogen with endometrial stimulation is the basic cause of
      dysfunctional uterine bleeding. The initial step in the evaluation of DUB
      includes detailed clinical history, followed by complete physical examination.
      Laboratory tests should include coagulation profile, complete blood count with
      platelet evaluation, and sometimes a serum pregnancy test. The treatment of DUB
      is related to the severity of symptomatology with the objective of stopping
      bleeding and preventing recurrences. Modern hormonal and other medical therapies
      enable physicians to treat DUB effectively, regardless of the cause. Surgical
      treatment, such as dilatation and curettage, is rarely indicated in the
      adolescent patient. The importance of continued follow-up in DUB cases should be
      underlined, until stabilization of ovulatory menstrual cycles.

PMID- 9238266
TI  - Hormonal regulation of N-cadherin mRNA levels in rat granulosa cells.
AB  - We have examined the ability of hormones to modulate the steady-state levels of N
      cadherin mRNA transcripts in aggregated and dispersed rat granulosa cell
      populations. Estradiol and follicle-stimulating hormone (FSH) had no effect on
      the levels of N-cadherin mRNA transcripts in aggregated granulosa cells. In
      contrast, these two hormones stimulated N-cadherin mRNA levels in dispersed
      granulosa cells. This is the first report that estradiol and FSH are capable of
      regulating N-cadherin mRNA levels. The results also suggest that the N-cadherin
      mRNA levels in dispersed and aggregated granulosa cells are regulated by
      different mechanisms.

PMID- 9238267
TI  - Anovulation and monophasic cycles.
AB  - Normal pubertal development is often considered complete when the adolescent
      experiences her first menstrual period. However, sexual maturity is not attained
      until the onset of regular ovulatory cycles, which may take a number of months to
      years to accomplish. This maturation process is orchestrated by a neuroendocrine
      cascade and modified by autocrine and paracrine events in the ovary. The control
      of these complex relationships takes time and could not be expected to be fully
      functional with menarche. During the first menstrual months, the hypothalamic
      pituitary-ovarian axis is immature, resulting in the secretion of only estrogens
      from the developing follicles; positive feedback to trigger ovulation develops
      later. Consequently, estrogen secretion is variable and unopposed by
      progesterone, which would normally be produced in ovulatory cycles. Estrogen-only
      primed endometrium often leads to irregular menstrual cycles with variable flow.
      Surprisingly, most adolescents do well and have few complaints in spite of these
      anovulatory cycles. If an abnormality is experienced with the menstrual cycle,
      once understood physiologically, it can be managed simply, by watchful expectancy
      or intermittent progestin therapy. Occasionally, sever menstrual bleeding is
      encountered, and in a proportion of these patients a thorough assessment will
      delineate an underlying medical problem that needs to be addressed. The
      management of these patients requires ingenuity from the pediatric reproductive
      endocrinologist and aggressive hormonal manipulation. Most patients do well, but
      some require long-term continuing care.

PMID- 9238268
TI  - The polycystic ovary syndrome. Pathogenesis, metabolic implications, and
      therapeutic approach.

PMID- 9238269
TI  - Adolescent polycystic ovary syndrome.

PMID- 9238270
TI  - Female sexual precocity.

PMID- 9238271
TI  - 21-hydroxylase deficiency.

PMID- 9238272
TI  - Late-onset congenital adrenal hyperplasia.

PMID- 9238273
TI  - Clinical syndromes of primary amenorrhea.

PMID- 9238274
TI  - Clinical syndromes of secondary amenorrhea.

PMID- 9238275
TI  - Bone mineral metabolism in diet-induced amenorrhea.
AB  - Spinal bone density of 41 girls with diet-induced amenorrhea (DA) was compared
      with that of the density of 22 subjects with premature ovarian failure (POF) of
      comparable age. The Z score values, as well as the estradiol levels, were not
      significantly different in the two groups. The duration of amenorrhea was
      significantly correlated to bone mass density in the DA population, especially
      when considering subjects with amenorrhea that had lasted longer than 20 months.
      A similar correlation between weight loss and BMD was evident. Although estradiol
      concentrations did not seem to be correlated to the Z score, FT3 and cortisol
      values exhibited, respectively, a negative and a positive correlation with spinal
      density. Cortisol seemed to act precociously, whereas FT3 acted later than
      cortisol.

PMID- 9238276
TI  - Luteinizing hormone resistance syndromes.
AB  - Luteinizing hormone (LH) plays its effects on ovarian and testicular cells
      through binding to a specific cell surface receptor. We recently described two
      kindreds with LH resistance due to abnormalities of the LH receptor (LH-R) gene.
      Affected XY members presented with severe or mild fetal undermasculinization
      (female external genitalia or micropenis) and primary hypogonadism, while an XX
      affected member showed normal pubertal development, increased plasma
      concentrations of LH, and amenorrhea. The first kindred included three XY
      phenotypic female siblings with Leydig cell hypoplasia and primary hypogonadism
      and a fully developed XX sister with elevated plasma concentrations of LH and
      amenorrhea. PCR amplification of genomic DNA and direct sequencing of the entire
      exon 11 of the LH-R revealed that all four affected individuals had a homozygous
      mutation (Arg554-->Stop codon) in the third cytosolic loop of the LH-R, which
      resulted in a truncated LH-R unable to transduce the hormonal signal. The second
      kindred included a 6-year-old XY boy with a micropenis and bilaterally descended
      testes, who demonstrated no response to exogenous human chorionic gonadotrophin
      postnatally. This patient had a nonconservative homozygous amino acid
      substitution (Ser616-->Tyr616) in the seventh transmembrane domain of his LH-R
      gene that was inherited from his heterozygous parents. The mutant receptor
      expressed in heterologous cells in vitro demonstrated no appreciable binding of
      125I-labeled hLH, nor did it confer cAMP responsiveness to LH. Homozygous
      inactivating mutations of the LH-R cause complete or mild testicular failure in
      genetic males, resulting in female external genitalia or micropenis and primary
      hypogonadism. Similar mutations in genetic females may cause failure of ovulation
      and corpus luteum formation, resulting in amenorrhea. Follicular growth and
      development are apparently sufficient to allow feminization at puberty.

PMID- 9238277
TI  - Amenorrhea in beta-homozygous thalassemia major.
AB  - Hemolytic anemias, and, in particular, beta-homozygous thalassemia, derange all
      vital organs. A shift of the survival curve to the right has been achieved,
      thanks to the intensive programs of blood transfusion; iron chelation; infectious
      control; and, most recently, bone marrow transplantation. Metabolic and endocrine
      abnormalities do occur, albeit in less severe forms in comparison to available
      data from 10 to 20 years ago, for example, osteopenia. The most commonly
      encountered hormonal disorder is the attenuation of gonadal function on a
      downstream basis, linked to iron deposition in the hypothalamic-pituitary
      gonadotropin axis. A transition, from low-amplitude endogenous GnRH pulses to
      apulsatility of LH patterns, precedes the inability of the pituitary gonadotrope
      to respond to the GnRH decapeptide administered either as an acute bolus
      injection or in a pulsatile manner for up to 7 days.

PMID- 9238278
TI  - Disturbances of menstruation in thyroid disease.
AB  - Both hyper- and hypothyroidism may result in menstrual disturbances. In
      hyperthyroidism, amenorrhea was described as early as 1840 by von Basedow. The
      most common manifestation is simple oligomenorrhea (decreased menstrual flow).
      Anovulatory cycles are very common. Increased bleeding may occur, but is rare in
      hyperthyroidism. Nowadays hyperthyroidism is diagnosed earlier than it once was,
      and so the clinical picture is generally milder. So, menstrual disorders are less
      common than in previous series. In a recent paper, 21.5% of 214 patients had
      disturbances in their cycle, compared to 50% in some older series. In
      hypothyroidism, on the contrary, polymenorrhea (increased menstrual bleeding) is
      more common. Defects in hemostasis may contribute to this. Anovulation may be
      represent. Fertility is reduced in both hyper- and hypothyroidism, and the
      outcome of pregnancy is more often abnormal than in euthyroid women. It is of
      interest that in juvenile hypothyroidism precocious puberty has been described.
      This is probably due to a "spillover" effect of the glucoprotein hormones: TSH,
      which is markedly increased in hypothyroidism, has a small FSH- and LH-like
      effect. Galactorrhea may also be present in hypothyroidism, possibly because TSH,
      the hypophyseal TSH-releasing hormone, increases the secretion of both TSH and
      PRL.

PMID- 9238279
TI  - Sports-related problems in reproductive function.

PMID- 9238280
TI  - Athletic amenorrhea.

PMID- 9238281
TI  - Etiopathology of endometriosis.
AB  - Although endometriosis is one of the most frequent problems in gynecology, its
      pathogenesis remains controversial and poorly understood. Many theories relating
      to the etiopathology of this disorder have been proposed. The celomic metaplasia
      hypothesis states that peritoneal mesothelium undergoes metaplasia, forming
      typical endometrial-like glands and stroma. The transplantation theory suggests
      implantation and subsequent growth of retrogradely shed, viable endometrial
      cells. The induction theory states that unknown substances released from shed
      endometrium induce undifferentiated mesenchyma to form endometriotic tissue.
      Regardless of which theory is correct, additional factors may be responsible for
      the expression of the disease. The possibility that the development and
      progression of endometriosis is associated with abnormal immune function and an
      inadequate response of the peritoneal defense system is currently the most recent
      hypothesis for the etiopathology of this disease.

PMID- 9238282
TI  - Endometriosis. Laparoscopy--diagnostic and therapeutic approaches.

PMID- 9238283
TI  - Modern approach to endometriosis.

PMID- 9238284
TI  - Female genital tract malignancies during puberty. Uterine and cervical
      malignancies.
AB  - Malignancies of the uterine corpus are extremely rare. Diagnostic and therapeutic
      procedures should be performed according to oncological principles with
      individually adapted treatment regimes. Clinical cancer of the cervix is rare in
      adolescence; the treatment is radical surgery. Preclinical stages, that is, CIN
      III (severe dysplasia, carcinoma in situ) and microinvasive cancer (stages Ia1,
      Ia2), are important, also because of their frequency. Diagnosis is based on
      colposcopy, cytology, direct biopsy, histological examination, and conization. In
      addition, virology (HPV) and DNA cytometry may become prognostic factors.
      Treatment consists of conization with an exact histological examination in serial
      sections as a basis for preserving the uterus. The sarcoma botryoides is
      localized in the cervix in adolescence, whereas it is in the vagina in infants
      and children.

PMID- 9238285
TI  - Ovarian malignancies in adolescence.
AB  - Ovarian malignancies, although rare during adolescence, constitute the most
      common genital neoplasms in this age group. Germ cell tumors account for the
      majority of cases (61.5%), whereas 20% belong to the common epithelial group and
      9.5% derive from sex cords and ovarian stroma. Dysgerminomas are the most
      frequent germ cell tumors. They are usually large and often secrete hormones and
      tumor markers that can be useful in monitoring the course of the disease.
      Diagnosis is often made in stage IA, and conservative surgery is the treatment of
      choice. In the epithelial neoplasm group, mucinous tumors are more common than
      usual (39.4% instead of 12%). The incidence of borderline tumors is also higher
      (30.3% versus 6-10%). Adnexectomy and, if needed, extirpation of peritoneal
      implants is considered adequate treatment. Sex cord-stromal tumors consist of
      epithelial (granulosa-Sertoli cells) and mesenchymal elements in a variety of
      combinations. Granulosa cell tumor is the most common subtype, presenting as the
      juvenile form in young females. It is of low malignant potential and is
      adequately treated with adnexectomy only.

PMID- 9238286
TI  - Oncogenes and onco-suppressor genes in female genital cancer.
AB  - Cancer is a multistep process resulting in the accumulation of genetic lesions in
      proto-oncogenes or tumor suppressor genes. In recent years, many biological
      studies have focused on the analysis of the genetic and molecular events
      occurring in genital tumors in order to identify genes involved in their
      initiation and progression. Understanding the genetic events that lead to
      initiation and progression of a disease remains an important challenge in
      gynecological research and ultimately may enable the development of better
      approaches for earlier diagnosis, in cases where current therapeutic strategies
      have a high cure rate.

PMID- 9238287
TI  - Oncogenic role of the Y chromosome.
AB  - The mechanism to explain the oncogenic role of genomic YDNA in dysgenetic
      individuals remains uncertain. At this time, it is a statistically significant
      association, but without a biological explanation.

PMID- 9238288
TI  - Malignant ovarian neoplasms. The place of conservative surgery.
AB  - Even though radical surgery is the treatment of choice in malignant neoplasms, a
      conservative approach may be considered in young patients who wish to preserve
      fertility, provided well-defined criteria are met and survival is not
      jeopardized. Unilateral, stage I, borderline (BT), germ cell (OGCT), sex cord
      stromal tumors, and grade I epithelial cancer can be treated with unilateral
      salpingoophorectomy (USO). If bilateral ovarian involvement is present, bilateral
      salpingoophorectomy (BSO) and preservation of the uterus can be considered.
      Cystectomy is rarely practiced, because of published contraindications, in
      borderline tumors. Complete surgical staging is mandatory in all cases regardless
      of the type of surgery (USO or BSO). Conservative management of more advanced
      disease is considered in a few BT and OGCT cases, provided it can be combined
      with successful cytoreduction. Adjuvant chemotherapy is necessary in almost all
      OGCT and epithelial cancers, although its role in BT and sex cord tumors is
      unspecified yet. Current knowledge suggests that conception is possible after
      conservative management for malignant ovarian neoplasms and chemotherapy does not
      cause obvious genetic malformations in the newborn.

PMID- 9238289
TI  - Acquired clitoral enlargement. Diagnosis and treatment.
AB  - Clitoral hypertrophy is usually seen in congenital malformations, specifically in
      intersexual stages of hormonal expression. Acquired clitoral hypertrophy is a
      relatively rare condition, and data in the literature concerning this problem are
      sparse. Articles usually consist only of case reports. Among the contributing
      factors in the etiology of acquired clitoral hypertrophy, the following three are
      the most frequent: (1) endocrinopathies including virilizing tumors of the
      ovaries or adrenals, (2) neurofibromatosis (of both clitoral subcutis and corpora
      cavernosa), and (3) pseudohypertrophy of the clitoris. The first step in
      correcting acquired clitoral enlargement must be to determine and stop the cause
      of the hypertrophy, followed by a period of simple observation. If clitoral
      enlargement does not disappear over time, surgical correction is necessary.

PMID- 9238290
TI  - Karyotype-phenotype correlation in females with X chromosome abnormalities.
AB  - In mammals, females have a pair of X chromosomes, whereas males have one X
      chromosome and one Y chromosome, which is much smaller and contains fewer genes
      than a X chromosome. One of the pair of X chromosomes is inactivated in females.
      The inactivated X chromosome is late-replicating, heterochromatic, and
      genetically unexpressed. An X inactivation center (XIC) located at a proximal
      region on Xq is thought to control inactivation of an X chromosome. There has
      been increasing scientific interest in the relationship between chromosomal and
      clinical findings in different chromosomal aberrations, whether affecting the sex
      chromosomes or the autosomes. The genetic and molecular implications of the
      karyotype/phenotype controversy have recently been considered with the aim of
      better understanding the interplay of specific genes carried on different
      chromosomes in organ development and differentiation. Karyotype/phenotype
      correlation showed the gradation of severity of clinical phenotype to be related
      to the number of X chromosomes.

PMID- 9238291
TI  - The ethics of somatic and germline gene therapy.
AB  - Somatic gene therapy research in humans is still searching for appropriate vector
      systems and remains experimental. Germline therapy is a major technical challenge
      and can be considered only for the future.

PMID- 9238292
TI  - Genetic screening for RET mutations in families with multiple endocrine neoplasia
      2 syndromes.
AB  - Mutations in the RET proto-oncogene have recently been recognized to be
      responsible for the inherited multiple endocrine neoplasia type 2 syndrome. As
      expected, Greek patients with MEN2 and FMTC carry RET mutations similar to those
      of other ethnic groups. In those regions of the gene that were analyzed,
      mutations were detected in six out of six families with classical MEN2A, three
      out of five of the families with familial MTC, and one case with MEN2B.
      Presymptomatic screening using DNA analysis has now replaced calcitonin
      stimulation tests in the offspring of families where the mutation has been
      characterized. The use of these methods will improve the prognosis in MEN2
      patients and will also reduce the psychological burden of risk for a potentially
      lethal disease on family members.

PMID- 9238293
TI  - Gonadal dysgenesis: fertility options.

PMID- 9238294
TI  - Adolescent sexuality.
AB  - Sex education is almost mandated in the United States. The data reviewing sexual
      activity in the adolescent population indicates that large numbers of women under
      the age of 19 who have unintended pregnancies are at risk for an increased
      frequency of sexually transmitted diseases which will affect their future. It is
      essential that good educational programs and preventive service programs be
      developed and mandated for the adolescent population. Experience in Western
      Europe demonstrates that the adolescent who has a proper education concerning
      sexual activity, sexually transmitted disease, and contraception is at lower risk
      for the many problems that we see in the United States. There must be cross
      cultural data that can be translated for use in the entire world. As the
      population of this world ages, we must protect those who are entering adulthood
      from being exposed to the STDs and undertaking the responsibility of parenting
      without having reached full maturity. The cost in dollars of the sequelae of
      adolescent pregnancies are great. These costs are not only financial, but also
      emotional and social, and they have a negative impact on the country in which the
      adolescent lives. We have a heavy responsibility as physicians and health care
      professionals to see that the adolescents of the world are given the knowledge
      and models to use to reduce the risk for pregnancy and the acquisition of a
      sexually transmitted disease.

PMID- 9238295
TI  - Sexually transmitted diseases and oral contraceptive use during adolescence.
AB  - Sexually transmitted diseases (STD) cause lower genital tract infections
      (cervicitis, vaginitis) or ascending infections of the fallopian tubes, and,
      possibly, pelvic inflammatory disease (PID). The syphilis bacterium, human
      immunodeficiency virus (HIV), and the hepatitis virus cause systematic disease.
      Although oral contraceptives (OCs) are the most reliable contraceptive method,
      they have limited anti-STD properties and their relationship with STDs remain
      unclear. Various mechanisms explain a protective role of OCs against STDs;
      however, in no way can OCs be considered a safe anti-STD contraceptive method,
      when compared to specific barrier methods, which provide both contraception and
      anti-STD protection. The above has been confirmed by a recent study performed in
      our institution where 10.3% and 6.9% of OC users presented a prevalence of
      Chlamydia trachomatis and Mycoplasma, respectively, when compared to 0% and 4.5%
      infection rates found among condom users. It is concluded that although OCs
      possess some anti-STD properties, mainly in the prevention of PID, they should be
      used in combination with a barrier method.

PMID- 9238296
TI  - Adolescent sexuality: an educational and counseling challenge.
AB  - A review of family-planning literature reveals that researchers adopt narrow
      definitions of sexual behavior and focus almost exclusively on risks of pregnancy
      and diseases. Little concern is shown in these articles about promoting the idea
      of more communicative, pleasurable, and egalitarian sexual relations among
      teenagers, because the focus is on avoiding behaviors that are defined as "high
      risk." In the United States, there is little evidence that these contraceptive
      based sex education programs have resulted in reduced sexual activity, diminished
      teenage-pregnancy rates, or increased effective contraceptive use. In Canada the
      clinical evidence is that existing prevention strategies are not working. In
      Sweden the increasing rates of STDs and teenage pregnancies in the late 1980s
      worried authorities. The figures were brought down in the 1990s by extensive
      efforts both in schools and at publicly funded adolescent health clinics and
      family-planning units. It has been shown that girls with good self-esteem and a
      sense of responsibility avoided pregnancies and STDs in follow-up studies. Girls
      with a high degree of risk-prone behavior or attitudes and girls with a
      problematic life situation and without adequate family support were those who
      became unintentionally pregnant and/or acquired an STD. Countries where sex
      education has been accepted, combined with widely spread family-planning services
      and abortion on demand, have the lowest pregnancy and abortion rates in the
      world. But even they could do better by putting sex education in its proper place
      in society and by using both old and new methods.

PMID- 9238297
TI  - The genital examination in suspected child sexual abuse. A diagnostic dilemma.

PMID- 9238298
TI  - Oral contraceptive compliance during adolescence.

PMID- 9238299
TI  - Long-acting hormonal contraception.
AB  - For 30 years, the combined oral contraceptive pill has been an almost automatic
      choice for effective contraception in sexually active adolescent women.
      Nevertheless, consideration of the criteria of a hypothetical "ideal"
      contraceptive suggests that long-acting progestogen-only methods may have
      considerable advantages for some adolescents. These would include greater
      efficacy, easier compliance, avoidance of estrogenic side effects, and
      potentially greater privacy. The disadvantages of menstrual irregularity,
      progestogenic side effects including weight gain, and the initial greater
      medicalization of the method, particularly implants, must be weighed against the
      wishes and preferences of the adolescent. A number of studies of the uptake and
      utilization of these methods in adolescence have arisen, particularly from the
      United States. These are reviewed together with experience from programs in the
      United Kingdom.

PMID- 9238300
TI  - Intrauterine contraception in adolescent women. The GyneFix intrauterine implant.
AB  - Pregnancy rates among adolescents have not decreased over the last 10 years,
      despite numerous efforts. To solve this important health problem, the major
      strategy recommended is to encourage contraceptive use among sexually active
      teenagers. An important means of obtaining this is by promoting methods that are
      not dependent on daily administration in order to avoid noncompliance. One such
      method (Norplant) has already shown to be much more effective than the
      combination pill in preventing pregnancy in adolescent women. The frameless
      intrauterine implant system (fixed, frameless, and completely flexible) has been
      studied since 1985 in women between 14 and 50 years of age. The results in young
      nulligravid women confirm its very high effectiveness (cumulative pregnancy rate
      at 36 months: 1.4%), its low expulsion rate (cumulative rate at 36 months: 0.9%)
      and its optimal tolerance (cumulative removal rate for medical reasons at 36
      months: 2.4%), resulting in a high acceptance of the implant and a high continued
      use. The system (GyneFix) offers long-term protection (5 years), and its
      insertion, with or without anesthetic, is easily accomplished in the office. The
      GyneFix should therefore be recommended as an excellent alternative for birth
      control pills for young women with low risk for STDs, especially when compliance
      is a problem, without an increased risk for complications and without systemic
      side effects. Removal of the device is accomplished by traction on the tail. It
      can also be used for emergency contraception and for insertion immediately after
      termination of pregnancy.

PMID- 9238301
TI  - Anti-STD vaginal contraceptive sponges.

PMID- 9238302
TI  - Minimizing the problem of poor compliance in adolescents. Clinical experience
      with a modern low-dose gestodene-containing oral contraceptive.
AB  - Adolescents represent a particularly difficult group with respect to compliance.
      Not only is incorrect pill intake a common problem, but unnecessary
      discontinuation also occurs regularly. Reasons for poor compliance are varied,
      but inadequate information and problems with cycle control and weight gain are
      particularly important. Choosing a well-tolerated oral contraceptive can help to
      improve compliance, and clinical experience from a large, multicenter trial
      suggests that monophasic gestodene (75 micrograms gestodene/30 micrograms
      ethinylestradiol) is a suitable preparation for this group of women. An
      investigation of 5,602 adolescents with an average age of 16.4 years found good
      contraceptive reliability and excellent cycle control. The incidence of spotting
      and breakthrough bleeding was low and declined during the course of the study.
      The preparation was tolerated well, and the incidence of adverse events was low,
      with only 4.4% of women withdrawing from the study due to adverse events. An
      increase in body weight was uncommon. At the end of the study, 85.0% of
      adolescents rated monophasic gestodene as good and 9.6% as satisfactory.

PMID- 9238303
TI  - Female adolescent sexuality. The risks and management.
AB  - Human sexuality goes through many stages from birth onward before reaching adult
      meaning and expression. Apart from the physical aspects, sexuality involves
      complex cognitive and social-emotional developmental processes including capacity
      for intimacy, affiliation, communication, mutual respect and responsibility. A
      variety of risks may affect sexuality development at any stage and facet of it.
      To support healthy sexuality functioning in the female adolescent, physicians
      need to identify early risk markers, some of which are biological and others
      intrapsychic or sociocultural. Identification should lead to preventative action
      in support of the adolescent.

PMID- 9238304
TI  - Epidemiology and site specificity of stress fractures.
AB  - Clinically, stress fractures appear to be a common overuse injury among athletes
      and in military recruits undertaking basic training; however, there is a lack of
      sound epidemiologic studies describing stress fracture occurrence in athletes.
      Few have directly compared stress fracture rates between sports to establish
      which poses the greatest risk for this injury. Furthermore, incidence rates,
      expressed in terms of exposure, have rarely been reported for stress fractures in
      athletes. Nevertheless, available data suggest that runners and ballet dancers
      are at relatively high risk for stress fractures. Although a gender difference in
      rates is clearly evident in military populations, this is less apparent in
      athletes. Other participant characteristics, such as age and race, may also
      influence stress fracture risk. The most common site of stress fracture in
      athletes is the tibia, although the site reflects the nature of the load applied
      to the skeleton. Stress fracture morbidity, expressed as the time until return to
      sport or activity, varies depending on the site. Generally, a period of 6 to 8
      weeks is needed for healing; however, stress fractures at certain sites, such as
      the navicular and anterior tibial cortex, are often associated with protracted
      recovery and, in some cases, termination of sporting pursuits.

PMID- 9238306
TI  - Stress fractures in the pediatric athlete.
AB  - Stress fractures are a source of significant sports disability in the growing
      athlete. Early diagnosis and treatment are paramount in the management of these
      injuries to minimize the morbidity associated with them. In addition, the
      identification of potential host and/or environmental risk factors, and education
      of athletes, parents, coaches and physicians about these risk factors are key in
      the prevention of stress fractures and other overuse injuries in the pediatric
      athlete.

PMID- 9238305
TI  - Stress injury to bone in the female athlete.
AB  - Stress injury to bone exists on a continuum, involving mechanical as well as
      hormonal and nutritional factors. Risk factors for stress injury include
      genetics, female gender, white ethnicity, low body weight, lack of weightbearing
      exercise, intrinsic and extrinsic mechanical factors, amenorrhea,
      oligoamenorrhea, inadequate calcium and caloric intake, and disordered eating.
      Prevention of stress injury to bone involves maximizing peak bone mass in the
      pediatric, adolescent, and young adult age groups. Maintaining adequate calcium
      nutrition and caloric intake, exercise and hormonal balance are important
      preventive measures in the adult years for optimizing skeletal integrity and
      preventing fractures. There are no prospective longitudinal studies to date that
      demonstrate a treatment that will increase bone density in female athletes with
      hypothalamic hypoestrogenic amenorrhea or disordered eating that have low bone
      density. Advances in genetic research show promise for future preventive and
      treatment strategies. More research is needed in this area to determine other
      factors that may be contributing to bone loss in these individuals, as well as to
      assess other treatment options leading to improvements in bone density and
      integrity.

PMID- 9238307
TI  - Running biomechanics.
AB  - With the interest of the general population in aerobic exercise, it is essential
      for physicians who treat sports injuries to understand the mechanism behind these
      problems. This article provided the reader with an introduction to the
      biomechanics of both walking and running to facilitate an understanding of the
      cause of these running injuries. It is hoped that with an improved understanding
      of the mechanics of walking and running, the reader will have an improved ability
      to diagnose these problems and improve the treatment of the injury.

PMID- 9238308
TI  - Footwear and stress fractures.
AB  - Causal factors associated with stress fractures include training errors, exercise
      surfaces, footwear, and anatomic abnormalities. Logically, footwear can play an
      important role in the development and treatment of stress fractures because foot
      loading, structure, and stability have a significant impact on the development of
      stress fractures. The important characteristics of athletic shoes in the
      development and treatment of stress fractures are reviewed in this article.

PMID- 9238309
TI  - Stress fractures. Clinical history and physical examination.
AB  - The incidence of stress fractures is increasing among competitive and
      recreational athletes as well as among children and the elderly. By understanding
      the continuum of bone's response to stress and maintaining an appropriate index
      of suspicion, the health care provider can diagnose these injuries appropriately.
      An accurate history and examination is essential and will differentiate stress
      fractures from other stress reactions. The more common stress fractures are
      discussed.

PMID- 9238310
TI  - Imaging of stress injuries to bone. Radiography, scintigraphy, and MR imaging.
AB  - Although conventional radiographs continue to be used as a primary method for the
      diagnosis of stress fractures, the limitations of radiography in early detection
      have been increasingly recognized. Advanced imaging techniques, including
      radionuclide methods, and more recently, MR imaging, have increasingly been
      employed in the assessment of stress fractures, and have provided valuable
      insights into the spectrum of stress-related changes to bone. This article
      reviews the diagnostic methods available to the clinician for detection of stress
      injuries to bone.

PMID- 9238311
TI  - The use of MR imaging in the assessment and clinical management of stress
      reactions of bone in high-performance athletes.
AB  - Based on experience, the authors believe that MR imaging is a useful tool in the
      assessment and management of stress fractures and stress phenomenum of bone. The
      use of standard, graded MR evaluation aides the assessment of a repetitive stress
      injury to bone by allowing a more accurate diagnosis of bone injury. This more
      accurate assessment has predictive value in estimating the duration of
      disability. The use of a standard, graded MR evaluation aides the management of
      repetitive stress injuries to bone by defining a low grade of stress fracture
      (i.e., grade 1 and 2) injuries and a high grade of stress fracture (i.e., grade 3
      and 4). This grading system has implications in the management of stress
      fractures, allowing more individualized treatment for the elite athlete.

PMID- 9238312
TI  - Femoral stress fractures.
AB  - Stress fractures are common overuse injuries attributed to the repetitive trauma
      associated with vigorous weightbearing activities. A high index of suspicion is
      necessary to diagnose stress fractures of the femur because the symptoms may be
      vague. The precipitating factors, whether related to training errors or medical
      conditions, should be thoroughly evaluated. Early diagnosis of distraction
      femoral neck stress fractures is critical to avoid serious complications. Femoral
      shaft stress fractures have excellent healing potential when diagnosed early and
      treated non-operatively. Stress fractures of the femoral condyles are uncommon,
      but should be included in the differential of knee pain.

PMID- 9238313
TI  - Metatarsal stress fractures.
AB  - Metatarsal stress fractures, resultant from increases in load due to altered
      mechanics of the foot, occur most frequently in athletes but also in patients
      with diminished function of the first metatarsophalangeal joint, neuropathy,
      metabolic disorders, and hindfoot malalignment. Diagnosis depends on a careful
      history and physical examination, with select use of imaging techniques.
      Nonoperative treatment usually is successful, but surgery (partially threaded
      cancellous screw with overdrilling of the fracture site to stimulate healing) is
      recommended for the athlete with a fifth metatarsal stress fracture or the
      nonathlete with a Torg-type-II or III injury. Malalignment or instability of the
      foot or ankle must be addressed at the time of surgical treatment.

PMID- 9238314
TI  - Stress fractures: general concepts.
AB  - This article is an overview of the general concepts about stress fractures,
      including history, epidemiology, and cause. The proper diagnosis, confirmation
      studies, and treatment regimens are presented. Finally, the timing of the
      athlete's return to sports, with stress fracture prevention measures are
      reviewed.

PMID- 9238315
TI  - Hair follicle growth controls.
AB  - Research in hair biology has embarked in the pursuit for molecules that control
      hair growth. Many molecules already have been associated with the controls of
      hair patterning, hair maturation, and hair cycling and differentiation. Knowing
      how these molecules work gives us the tools for understanding and treating
      patients with hair disorders.

PMID- 9238316
TI  - Growth factors in hair organ development and the hair growth cycle.
AB  - Growth factors are polypeptides that regulate growth and differentiation of many
      cell types. Different growth factor families including the epidermal growth
      factor (EGF)-related ligands, fibroblast growth factors (FGF), transforming
      growth factor-beta (TGF-beta), insulin-like growth factor (IGF), hepatocyte
      growth factor/scatter factor (HGF/SF), and platelet-derived growth factor (PDGF)
      have been shown to be crucial for the regulation of the hair cycle and hair
      growth. Growth factors and their receptors have been localized to the skin and
      hair follicles. Their biological activities on cells comprising the hair follicle
      have been tested in vitro and increasingly in transgenic mice. Herein we review
      selected important aspects of growth factors with regard to the hair organ, its
      development, and the hair growth cycle.

PMID- 9238317
TI  - Dermal-epidermal interactions. Adult follicle-derived cell populations and hair
      growth.
AB  - Intrinsic dermal-epidermal interactions are central to the development and growth
      of hair. This article describes investigations into the inductive properties of
      specific dermal and epidermal cell populations from adult follicles by means of
      cell culture and in vivo implantation. It highlights the inductive powers of
      cultured dermal papilla cells and the more recent finding that the germinative
      epidermal cells of the lower follicle also can stimulate hair growth. How the
      reconstruction of a hair follicle from its constituent parts has been achieved is
      described. The significance of these findings is considered with reference to
      human hair growth, tissue engineering, and the prospects for elucidating the
      molecular signalling mechanisms that underpin dermal-epidermal interplay.

PMID- 9238318
TI  - The use of dermal papilla cells in studies of normal and abnormal hair follicle
      biology.
AB  - The mesenchyme-derived dermal papilla plays a major regulatory role in the
      complex cell biology of the hair follicle. The ability to culture dermal papilla
      cells from a range of species and particularly a range of normal and disordered
      human hair follicles has enabled the development of a powerful new model system
      for investigating hair follicle biology. Already these studies have reinforced
      the importance of dermal papilla cells in initiating new follicle growth and in
      androgen action in human hair follicles. The retention of hair growth inducing
      capabilities and characteristics that reflect their in vivo responsiveness to
      androgens in culture means that they offer a potentially useful approach despite
      significant drawbacks in working with the cells themselves. Further studies using
      dermal papilla cells may well elucidate key molecules involved in hair biology in
      health and disease and, thereby, lead to better therapeutic regimens.

PMID- 9238319
TI  - Whole hair follicle culture.
AB  - In this article the authors have reviewed the historical background behind the
      organ culture of whole hair follicles. The methods developed by the authors and
      others for the isolation and whole organ maintenance of hair follicles from both
      human and other species are described. How whole organ models have been used to
      further understanding of the biology of the hair follicle and how they may be
      used in the future are discussed.

PMID- 9238320
TI  - The growth of human hair in nude mice.
AB  - The author reviews published papers on human hair growth in nude mice. There is
      evidence from various sources indicating that grafting of human scalp onto nude
      mice does not modify significantly morphogenesis, hair follicle structure and
      function, and composition of the newly grown hair fiber. On the basis of personal
      observations, the authors further highlights the results obtained in genetic hair
      defects. Hints are given as to the potential use of the model for drug discovery
      programs as the product can be used on the human target at early stages of drug
      development.

PMID- 9238321
TI  - Mouse models for the study of human hair loss.
AB  - A comparison has been presented to illustrate many of the similarities in
      patterns of disease between mouse and human hair follicle diseases and how
      various mouse mutations can be used as research tools to investigate these
      observations. The powerful genetic tools available for investigating mouse
      mutations and human homologues will continue to result in many breakthroughs in
      the understanding of hair follicle biology and pathology. Many more mouse
      mutations are available than are described here. Information on these mutations
      fills books and computer databases, providing an unlimited resource.

PMID- 9238322
TI  - Hair keratinization in health and disease.
AB  - The cells of the epidermis and its derivative, the hair follicle, undergo
      processes of terminal differentiation that involves the synthesis and assembly of
      classes of protein and enzymes to form the stratum corneum of the epidermis, and
      the hair fiber and its cuticle. Using genetic linkage and DNA sequencing methods,
      we now know that mutations in several genes encoding epidermal keratins or a
      transglutaminase enzyme cause ichthyosis-related diseases. Similar methods have
      now suggested that mutations in hair keratin genes underlie some cases of
      monilethrix, and a deficiency in a cuticle lipid metabolizing enzyme causes maple
      syrup urine disease. It is to be expected that further application of these
      methods will elucidate the molecular bases of other genetic hair diseases.

PMID- 9238323
TI  - Relationship between follicular nerve supply and alopecia.
AB  - The emergence of new technologies such as the combination of immunohistochemical
      techniques with laser scanning confocal microscopy allows one to observe and
      project the three-dimensional perifollicular innervation in tissue sections
      measuring up to 200 microns. This technology opens the door to making new
      discoveries about the innervation of the hair follicle. As new information is
      generated about the cutaneous sensory nervous system, neuropeptide expression,
      and the modulation of inflammatory and proliferative processes by the nervous
      system in the skin, it is likely this knowledge will be applied to enhance our
      understanding of the biology of the hair follicle in both the normal and diseased
      state.

PMID- 9238325
TI  - Genetic control of cytokines. Cytokine gene polymorphisms in alopecia areata.
AB  - It is likely that alopecia areata is a multifactorial disease determined by a
      combination of genetic and environmental factors. The interaction of
      susceptibility genes with environmental factors gives rise to the disease
      phenotype, and then genetic modifying factors determine the extent of the
      inflammatory response and thereby the clinical outcome. Cytokines regulate the
      inflammatory response. Polymorphisms in these genes may therefore determine the
      amount of a cytokine that is produced in response to an environmental trigger
      such as a bacterial or viral infection.

PMID- 9238324
TI  - The pathogenesis of alopecia areata.
AB  - Knowledge of the disease mechanisms in alopecia areata is discussed in the light
      of progress in hair biology, immunology, and genetics. A disease model is
      presented incorporating polygenic determination of disease severity and
      susceptibility with largely unknown trigger factors responsible for initiating
      clinical disease expression. Experimental systems including animal models for
      alopecia areata offer new opportunities for investigation of alopecia areata and
      developing novel therapies.

PMID- 9238326
TI  - Heritable factors distinguish two types of alopecia areata.
AB  - Alopecia areata (AA) has been shown to be associated with the inheritance of HLA
      class II alleles. HLA-DQ3 appears to be the general susceptibility allele for AA.
      Patients with long-standing disease patterns, namely, longterm patchy AA and long
      term alopecia totalis and alopecia universalis (AT/AU), can be differentiated by
      their particular HLA associations. Long-standing AT/AU patients have unique and
      highly significant associations with HLA antigens DR4, DR11, and DQ7. A complex
      of early onset, disease severity, family incidence, and associations with HLA DR
      antigens are characteristic of long-standing AT/AU as distinct from long-standing
      patchy AA.

PMID- 9238327
TI  - A simplified approach to the diagnosis of alopecia.
AB  - Specific types of alopecia can be readily identified by history and physical
      examination with a high degree of accuracy in 97% of cases. Although some
      confirmatory laboratory studies may be required, two elements of the medical
      history and four elements of the physical examination can lead a dermatologist
      knowledgeable in the common scalp diseases to a rapid diagnosis. The key elements
      of history are age and duration of alopecia. The key elements of the examination
      are scalp status, pattern of loss, pull test results, and the integrity of the
      follicular units.

PMID- 9238329
TI  - Photographic documentation of hair growth in androgenetic alopecia.
AB  - The challenge of useful serial photographic documentation of hair loss can be met
      by using a regimented approach at each photographic session. Patient outcomes
      that are better documented allow for more informed decisions to be made about the
      course of therapy by both the physician and the patient.

PMID- 9238328
TI  - Androgen metabolism as it affects hair growth in androgenetic alopecia.
AB  - Androgens, in combination with a genetic susceptibility, have been demonstrated
      to be required for the development of androgenetic alopecia. Disturbances in
      androgen metabolism or target organ sensitivity are thought to underlie the
      pathophysiology of the condition. Observations of patients with disorders of
      androgen metabolism or function have determined the basic physiology involved in
      regulation of hair growth by androgens at selective body sites. More recently, in
      vitro studies of scalp skin and hair follicles have begun to define specific
      alterations in androgen metabolism at the local level that may play a key role in
      pathogenesis. The prominent role of 5-reductase in these studies suggests that
      inhibitors of this enzyme may provide new therapeutic opportunities for patients
      with androgenetic alopecia.

PMID- 9238330
TI  - Chronic telogen effluvium.
AB  - Chronic telogen effluvium is not uncommon. It is a form of diffuse hair loss
      affecting the entire scalp for which no obvious cause can be found. It usually
      affects women of 30 to 60 years of age who generally have a full head of hair
      prior to the onset of shedding. The onset is usually abrupt, with or without a
      recognizable initiating factor. The degree of shedding is usually severe in the
      early stages and the hair may come out in handfuls. Chronic telogen effluvium has
      distinctive clinical and histologic features that are usually diagnostic. Chronic
      telogen effluvium contrasts with classic acute telogen effluvium by its
      persistence and its tendency to fluctuate for a period of years. Patients are
      particularly troubled by the continuing hair loss and fear total baldness.
      Repeated reassurance that the condition represents shedding rather than actual
      hair loss and does not cause complete baldness is necessary. Chronic telogen
      effluvium does appear to be self-limiting in the long run.

PMID- 9238331
TI  - Treatment of alopecia areata.
AB  - Some individuals question whether any treatment is effective in severe alopecia
      areata. Certainly many patients, especially those with mild disease, experience
      spontaneous hair regrowth; however, results of double-blind studies clearly
      indicate that some treatments do promote hair regrowth even in those with
      extensive disease. Some patients never show either spontaneous or treatment
      related hair regrowth; others experience hair regrowth only while maintained on
      treatment, repeatedly losing hair within a few weeks of discontinuing treatment
      and regrowing it within several weeks after restarting treatment. Some patients
      who have been responsive to treatment may experience exacerbation of their
      disease such that even high-dose systemic steroids do not prevent the development
      of alopecia universalis. Some treatments appear to work on some patients some or
      all of the time, but no treatment appears to work on all patients all of the
      time. We would suggest a few practical points that we find useful: To maximize
      the potential for cosmetic hair growth in alopecia areata that is extensive or
      flaring, treat the entire scalp instead of "chasing" patches. Do not change any
      topical treatment sooner than 3 months after starting it; early regrowth may
      first be present at 3 months. Cosmetic regrowth may take a year or more to
      achieve. Maintenance treatment increases the likelihood of maintenance of
      cosmetic hair growth, but patches of hair loss may still come and go. Atopic
      patients who experience seasonal hair loss may benefit (ie, have less severe hair
      loss flares or respond more readily to topical therapy) by using an antihistamine
      or mast cell stabilizer prophylactically. Whether one looks at the therapeutic
      cup as half full or half empty, most patients urge us to continue to try to find
      safe, effective long-term treatments for this disease.

PMID- 9238332
TI  - Topical immunotherapy in alopecia areata. What, how, and why?
AB  - At present the induction and elicitation of an ACD with potent contact allergens
      such as DCP appear to be the most effective, but still not definitively curative,
      approach in treating extensive forms of AA. Experimental data suggest that
      cytokines and growth factors such as IL 1 beta are involved in the pathogenesis
      of AA as well as the therapeutic effect mediated by contact sensitizers. It seems
      reasonable to assume that factors inherent in the late phase of ACD modulate a T
      cell mediated mechanism responsible for AA, thus inducing hair regrowth. Such
      counteracting activities are most likely mediated by proinflammatory cytokines
      such as TNF-alpha, IL-10, or TGF-beta 1. This hypothesis may oversimplify the
      underlying immunologic mechanisms, but the effectiveness of topical immunotherapy
      in AA would be compatible with this concept. This mode of treatment is, however,
      a rather rough approach and recurrences are possible. It is hoped that advances
      in basic science will eventually allow us to find a more specific mode of
      treatment.

PMID- 9238333
TI  - Loose anagen syndrome and loose anagen hair.
AB  - Loose anagen syndrome, or loose anagen hair, is a recently described condition of
      unknown etiology that may be under-recognized. The typical patient is a child
      with sparse fine hair that can easily be pulled out. The diagnosis is confirmed
      by microscopic examination of firmly pulled hairs, many of which are in the
      anagen phase but lacking an inner and outer root sheath and demonstrating a
      ruffled cuticle. Some presentations of alopecia areata may be confused with this
      condition, but the pull test analysis serves to differentiate them. A variety of
      theories have been postulated to explain the pathophysiology of loose anagen
      syndrome. In some cases, there is an autosomal dominant pattern of inheritance.
      In most cases, this condition spontaneously improves with age.

PMID- 9238334
TI  - An update of hair shaft disorders.

PMID- 9238335
TI  - Cicatricial alopecia.
AB  - Scarring alopecias are of diverse etiology and pathogenesis. They may be
      histologically classified as primary or secondary, depending on involvement of
      reticular dermis. The most important primary scarring alopecias include
      pseudopelade, lichen planopilaris, and diffuse scarring of the vertex in African
      Americans. The most important secondary scarring alopecias include folliculitis
      decalvans and late-stage lupus erythematosus.

PMID- 9238336
TI  - What's new in hair replacement surgery.
AB  - The "isolated frontal forelock," "bridge over troubled waters," and lighter
      density coverage of larger areas are new options for hair transplant patients.
      Alopecia reductions are playing an increasingly important role in overall
      planning after a period in which they had at least appeared to be losing
      popularity. Tumescent anesthesia in the donor or recipient area results in safer,
      more comfortable, and effective anesthesia. Total excision techniques in the
      donor area as well as improvements in minigrafting represent important advances
      that are being utilized by an increasing number of practitioners. Carbon dioxide
      lasers are likely to play an important role in hair replacement surgery.

PMID- 9238337
TI  - Antiandrogen and hormonal treatment of acne.
AB  - In the treatment of acne in women, the use of antiandrogens and other hormonal
      approaches is a valuable alternative to standard therapy. These treatments that
      are based on physiologically sound principles produce gratifying results in
      selected women with acne, and are the primary treatment for women with hirsutism.
      The drugs discussed in this article include spironolactone, cyproterone acetate,
      flutamide, oral contraceptives, corticosteroids, finasteride, and gonadotropin
      releasing hormone agonists. Patient selection, pretreatment evaluation, and case
      studies also are discussed with an emphasis on practical applications.

PMID- 9238338
TI  - A classic cAMP responsive element in the promoter region of the alpha 1-GABAA
      receptor subunit has non-classic properties.
AB  - The cAMP responsive element binding protein (CREB) and the glucocorticoid
      receptor (GR) have been reported to bind to a 60 bp promoter fragment of the
      alpha 1-GABAA receptor gene containing a classic cAMP-responsive element (CRE).
      We inserted this fragment into a hormone responsive element-deleted mouse mammary
      tumor virus promoter controlling the expression of luciferase. Activation of GR
      showed no significant change in luciferase expression, but hormone induction by
      forskolin revealed a reduction in neuronal cell lines. Furthermore, we
      demonstrate that cellular factors from neuronal cells can bind to the CRE
      containing promoter fragment, although competition by unlabeled CRE and GRE oligo
      nucleotides is not present. Mutation of the CRE site and deletion of neighboring
      DNA sequences indicate that the promoter is probably associated with a complex of
      different regulatory factors.

PMID- 9238339
TI  - Superoxide dismutase activity in early and advanced Parkinson's disease.
AB  - Superoxide dismutase (SOD) is an enzyme system that is implicated in the oxidant
      stress model of Parkinson's disease (PD) pathogenesis. This study was designed to
      assess SOD activity in whole blood and red blood cells of PD patients in early
      and advanced stages of the disease. Fifteen PD patients in stage I and II (group
      A) and 15 in stage III and IV (group B) as well as 15 normal controls were
      included in the study. SOD activity was assessed in whole blood and red blood
      cells. Group B patients showed a statistically significant decrease of SOD
      activity in whole blood and in red blood cells. A negative correlation between
      SOD activity and duration of the disease was observed, while there was no
      relationship between L-Dopa treatment and SOD activity. Our results indicate that
      a defect in SOD activity develops over time in PD. Whether this is a later
      manifestation of antioxidant mechanism deterioration or simply an epiphenomenon
      remains unclear.

PMID- 9238340
TI  - Plasma met-enkephalin and catecholamine changes during the menstrual cycle and
      pain episode in menstrual migraine.
AB  - In order to explore opioid, sympathetic and hormonal parameters, we evaluated
      plasma met-enkephalin (ME), catecholamines (CA), estradiol (E2) and progesterone
      (P) in different phases of the menstrual cycle and during menstrual crisis in
      women suffering from menstrual migraine (MM) and in controls. No differences in P
      and E2 were found between controls and patients. We observed an increase in
      plasma ME and a decrease in plasma free norepinephrine (NE) levels on day 22 in
      MM group and an increase in plasma ME, free NE and total epinephrine (E) during
      pain. Our data, although obtained in a small number of patients, show clear
      modifications in plasma ME and in the sympathoadrenal function, not only during
      pain but also in the mid luteal phase.

PMID- 9238341
TI  - Somatosensory evoked potentials in migraine.
AB  - Twenty-six patients suffering from migraine with aura and without aura were
      examined using somatosensory evoked potentials (SEPs) during the intercritical
      phase. The mean amplitude of the prerolandic component was significantly reduced
      in migraine patients with and without aura on the right hemisphere; the ratio
      between the parietal N20/P25 and the prerolandic P22/N30 was significantly
      enhanced in migraine groups over the left and the right hemisphere. A significant
      interside asymmetry of the N30 amplitude was observed in the migraine with aura
      group in comparison with control subjects. The occurrence of SEP abnormalities
      was not correlated with the age of the patients, with illness duration or with
      the frequency of migraine attacks. SEP abnormalities observed in migraine with
      and without aura may have an underlying primary neural disorder probably based on
      a chronic dopaminergic dysfunction.

PMID- 9238342
TI  - Characteristics of the autonomic response in the visually evoked reflex in
      humans.
AB  - This study aimed (a) to investigate the effect of the visuogenic reflex on the
      skin microcirculation of the hand and foot, and (b) to compare it to that evoked
      by thermal stimuli. Fifteen volunteers took part in this study. The laser Doppler
      technique was used for measuring blood flow (BF). The results showed that a flash
      of light with a duration of 300 ms caused a significant decrease in BF (mean 38.4
      +/- 14.8%) in 10 out of 15 subjects in the hand but not in the foot. The latency
      was 5.05 +/- 0.7 s and the duration 7.2 +/- 1.8 s. The reaction did not show a
      significant change when a longer stimulus of 14 s was applied. Repetitive stimuli
      evoked habituation (p < 0.01). There is significant difference (p < 0.01) between
      autonomic responses to visuogenic and to calorically evoked reflexes.

PMID- 9238343
TI  - Elective neurotraumatology and therapeutic strategies in early post-trauma.
AB  - The aim of elective neurotraumatology is to outline new and valid therapeutic
      strategies in early post-trauma in order to obtain a more favourable long-term
      outcome for cranial and spinal trauma patients than usually achieved with
      conventional intensive therapies. After a critical review of all drugs and
      measures currently used for the treatment of damage due to cerebral trauma and a
      brief mention of new agents still being studied, the results of a retrospective
      study of 128 patients with severe head injury are reported. For all patients a
      complete clinical and pharmacological history of their traumatic event, which had
      occurred from 5 to 14 years before the present evaluation, was available. Eighty
      nine had undergone traditional therapies and 39 had been given complementary
      neuroprotective drugs, variously associated with traditional therapies. There was
      no statistically significant difference between the groups in terms of the global
      clinical outcome, (assessed by a 5-point scale: death, worsening, unchanged
      condition, improvement, recovery), and some sequelae, such as decubitus,
      impairment of sphincter control, neurological focal deficits and post-traumatic
      epilepsy. On the contrary, cognitive impairment and depression resulted
      statistically less frequent in patients who underwent conventional therapies and
      early complementary neuroprotective treatments than in the controls. In
      conclusion it would be very interesting to perform controlled clinical studies to
      confirm these preliminary results and the effectiveness of early neuroprotection
      on the long-term clinical outcome of patients with severe head injury. The
      therapeutic approach in early post-trauma is still not completely standardised
      and the purpose of elective neurotraumatology is to emphasise and promote the
      importance of such a standardisation.

PMID- 9238344
TI  - Need more education about NP role.

PMID- 9238345
TI  - What about chiropractors?

PMID- 9238346
TI  - Clinical guidelines: hepatitis B.

PMID- 9238347
TI  - Retinopathy of prematurity.
AB  - Retinopathy of prematurity is a condition that can be ameliorated for premature
      infants. Such intervention strategies include careful administration of oxygen in
      incubators through monitoring of blood gases, early detection of ROP utilizing
      the international evaluation of ROP diagnosis, and timely drug and surgical
      interventions for premature infants. These strategies apply to all premature
      infants but especially to those whose birth weight was less than 1,500 grams and
      who received oxygen for a prolonged period of time.

PMID- 9238348
TI  - Emergency care for snake bites.

PMID- 9238349
TI  - Primary care diagnosis of acute abdominal pain.
AB  - The abdomen, as the largest cavity in the body, holds both fixed as well as
      relatively mobile organs, which when either diseased, traumatized,
      malfunctioning, or infected may present a wide and diverse range of signs and
      symptoms. Clues to the origin of abdominal pain can be well-localized or referred
      and quite obtuse. This article reviews the surface anatomy of the abdomen, the
      types of abdominal pain, approach to the patient with abdominal pain, and history
      taking and physical examination. Adjunctive studies, which might help to reduce
      the differential diagnosis, are mentioned. The goal of this article is to help
      the reader formulate an accurate diagnosis in a timely manner via a complete but
      also well-focused physical examination; attention is paid to a comprehensive
      differential diagnosis to include common and not so common causes of acute
      abdominal pain. Intra-abdominal sources of abdominal pain include: peritonitis,
      bowel obstruction, and vascular disorders. Extra-abdominal sources of abdominal
      pain include the thorax, pelvis, and the abdominal wall. Some metabolic and
      neurogenic sources of abdominal pain are examined. Life-threatening causes of
      abdominal pain include ectopic pregnancy, acute myocardial infarction, abdominal
      aortic aneurysm, splenic rupture, and obstructed bowel. Discussion of these
      entities concentrates on the initial presentation of the patient, typical
      progression of symptoms, and appropriate initial treatment as well as referral.
      The process of ruling out emergent abdominal pain is also examined.

PMID- 9238350
TI  - The sequelae of childhood sexual abuse: a primary care focus for adult female
      survivors.
AB  - Researchers have increasingly demonstrated that 15% to 30% of all women have been
      sexually abused as children. Information on the emotional, behavioral, and
      cognitive sequelae of this abuse has been available. Most recently, a literature
      on the somatic and medical sequelae has developed. This article reviews this
      literature and discusses its implications for primary care providers. Survivors
      are likely to suffer from insomnia, gastrointestinal problems, obesity, chronic
      pain, headache, and somatization, and they are frequent utilizers of primary care
      services. Specific suggestions about history taking, physical examination, and
      referrals are given to ensure that survivors receive care that is sensitive,
      supportive, and competent. The article also discusses the dynamics of abuse and
      how they relate to the ongoing relationship between the primary care provider and
      the survivor of sexual abuse.

PMID- 9238351
TI  - Lichen sclerosus: early diagnosis is the key to treatment.
AB  - Lichen sclerosus of the vulvar is an often misdiagnosed and chronic gynecologic
      disease. Women of any age can be affected, but it is most common in the
      perimenopausal and postmenopausal years. The treatment for lichen sclerosus is
      limited with no cure. The current treatment is a lifelong procedure and may not
      prevent the progression of the disease. The primary treatment for lichen
      sclerosus is testosterone ointment, which may cause unwanted side effects.
      Complications arising from vulvar lichen sclerosus include loss of vulvar
      structure and fusing of labia which causes covering of the clitoris. Vulvar
      lichen sclerosus may also cause painful intercourse and defecation. Due to the
      intense pruritus, excoriation of the area occurs. This information can help the
      clinician to detect the disease early and start treatment before serious
      complications begin. Diagnostic and treatment information is provided in this
      article to help the clinician understand the nature of this disease.

PMID- 9238352
TI  - Hepatitis B immunization/prophylaxis: recommendations for adults/older adults.

PMID- 9238353
TI  - Update on recommendations for HIV postexposure prophylaxis.
AB  - Using postexposure prophylaxis is likely to reduce the risk of infection from HIV
      exposure in health care workers, though data confirming this is limited.
      Initiation of therapy in a timely fashion with combination antiretroviral agents
      may be essential, but weighing risk of exposure to possible toxicity is also
      important. Careful follow-up including medication monitoring, HIV antibody
      testing, and supportive counseling are an integral part of PEP therapy.
      Identifying, ahead of time, key medical personnel to provide expertise in these
      issues could be helpful both in preventing delays, and in reducing fear and
      anxiety. Recommended medications should be available in emergency rooms and
      employee health clinics for this purpose.

PMID- 9238354
TI  - Choosing a practice: key issues to consider.

PMID- 9238355
TI  - Clinical privileging for advanced practice nurses.

PMID- 9238356
TI  - Hormone replacement therapy.
AB  - More than 40 million women in the United States are now going through or are past
      menopause. Another 3.5 million or more will reach midlife in the next decade. As
      their life expectancy increases (mean life expectancy of women is now
      approximately 84 years), so does the need for therapeutic regimens related to
      reproductive function and aging in woman. Few medical treatments available to
      menopausal and postmenopausal women have as much potential benefit as well as
      possible health risks as hormone replacement therapy (HRT). Despite the
      increasing amount of scientific data available regarding the benefits of HRT, a
      degree of uncertainty still remains, both in the minds of some women, and with
      some health professionals, regarding the risks associated with long-term therapy.
      Even though the literature is voluminous, contradictory, and unclear, health
      providers must be able to keep abreast of current knowledge about the benefits,
      risks, and unknowns of these drugs. The purpose of this article is to provide a
      review and an update on the types of hormones available for HRT, their
      pharmacology and pharmacokinetics, and their risks, benefits, and
      contraindications. Newer products, specially compounded formulas, new regimens,
      and new modes of delivery that offer women alternatives and allow care to be
      individualized are described. In addition, some of the ongoing management
      dilemmas that practitioners face with the woman who chooses HRT are presented
      with practical solutions and suggestions.

PMID- 9238357
TI  - Fine-needle aspiration biopsy.

PMID- 9238358
TI  - Fine-needle aspiration diagnosis of HIV-related conditions.
AB  - The authors highlight the more common conditions that can be diagnosed by FNA,
      offering examples to illustrate how material obtained from FNA can be triaged for
      effective patient management. They also discuss the HIV-related changes found in
      body fluids and other cytologic specimens, such as those from bronchoalveolar
      lavage and induced sputum.

PMID- 9238359
TI  - Fine-needle aspiration of the breast.
AB  - Fine-needle aspiration of the breast has become increasingly important as the
      standard of care for the evaluation of a breast lump. In this chapter the authors
      present a detailed discussion of breast masses, the basics of palpation and
      aspiration, and the evaluation of FNA smears in both benign and malignant breast
      disease.

PMID- 9238360
TI  - Fine-needle aspiration of the salivary glands.
AB  - Fine-needle aspiration is increasingly used in community practices for the
      diagnosis of salivary gland lesions, and it often renders an unequivocal
      diagnosis. This chapter discusses in detail the technical considerations of FNA,
      non-neoplastic and inflammatory conditions, benign neoplasms, common malignant
      neoplasms, and rare malignant neoplasms.

PMID- 9238361
TI  - Fine-needle aspiration cytology of the thyroid.
AB  - Fine-needle aspiration of the thyroid, in experienced hands, is an extremely
      specific and sensitive tool. The authors provide an in-depth discussion of FNA
      for both benign and malignant lesions of the thyroid, and they offer a flow chart
      with diagnostic indicators that also clarifies areas of overlap between lesions.

PMID- 9238362
TI  - Fine-needle aspiration of lymph nodes: use of flow cytometry immunophenotyping.
AB  - Fine-needle aspiration of lymph nodes can be used successfully in the clinical
      work-up of lymphadenopathy. The procedure has some limitations, some of which can
      be overcome by using such ancillary studies as flow cytometry or
      immunophenotyping. The authors discuss the use of these techniques in
      establishing definitive diagnosis of the most common and well-recognized
      lymphadenopathies.

PMID- 9238363
TI  - Fine-needle aspiration biopsy of the liver: diagnostic problems.
AB  - FNA of the liver is a diagnostic test that can be used to identify the vast
      majority of neoplasms of a primary or metastatic nature. Well-prepared FNA
      samples, in conjunction with cell button preparations, and correlation with the
      clinical history are necessary for optimal results. Even with the best of
      samples, however, well-differentiated hepatocellular neoplasms, both benign and
      malignant, and rare lesions still can remain difficult to diagnose by FNA.

PMID- 9238364
TI  - Fine-needle aspiration of the pancreas.
AB  - In patients with a palpable or radiographically identified pancreatic lesion, FNA
      is a safe and accurate procedure for procuring diagnostic tissue. Complications
      of the procedure are rare, and the morbidity and mortality are considerably less
      than that associated with open laparotomy and wedge biopsy. The most common
      complication associated with pancreatic FNA is acute pancreatitis.
      Contraindications to FNA include an uncorrectable bleeding diathesis, marked
      ascites, and suspected hydatid cyst. The accuracy of FNA for diagnosing
      pancreatic adenocarcinoma is about 80%, and the overall sensitivity can be
      increased by multiple needle passes. Close communication and collaboration among
      the clinician, radiologist, and pathologist can help assure that suitable tissue
      is obtained and maximize the diagnostic yield of the procedure. To this end, the
      presence of the pathologist or a cytotechnologist at the FNA procedure is
      desirable to assess the tissue as it is procured. The vast majority of malignant
      pancreatic neoplasms are ductal adenocarcinomas. Thus, the primary diagnostic
      problem facing the pathologist is differentiating adenocarcinoma from benign
      and/or inflammatory processes. The three key cytologic features that aid in this
      distinction are anisonucleosis, increased nuclear size, and nuclear molding. When
      all three of these features are present, the sensitivity of the procedure
      approaches 98%, and its specificity approaches 100%.

PMID- 9238365
TI  - Fine-needle aspiration of the head and neck.
AB  - Fine-needle aspiration cytology is a valuable technique in the work-up of nodules
      and masses arising within the head and neck. Squamous cell carcinoma is present
      most often, and because of this relative frequency, the primary utility of needle
      aspiration cytology is in the confirmation or exclusion of this diagnosis. FNA is
      particularly helpful in the work-up of cervical masses and nodules because biopsy
      of cervical adenopathy should be avoided unless all other diagnostic modalities
      have failed to establish a diagnosis. As such, needle-aspiration cytology
      represents an accurate, inexpensive, and rapid technique for elucidation of the
      etiology of cervical adenopathy. The majority of aspirates from cervical lymph
      nodes will disclose either reactive lymphadenopathy or metastatic squamous cell
      carcinoma. Occasional nodules will be due to lymphoma. While primary diagnosis of
      lymphoma by needle-aspiration cytology is generally not considered definitive, it
      is helpful in clarifying the nature of the process and the direction additional
      diagnostic tests should take. Similarly, establishing the presence of carotid
      body tumors, brachial cleft cysts or epidermal inclusion cysts excludes
      metastatic carcinoma and negates the need for open biopsy as well as allaying
      concerns on the part of both clinician and patient. Fine-needle aspiration of
      lesions within the mouth, oral pharynx, nasopharynx, and nasal sinuses has
      similar diagnostic goals, in that eliminating squamous cell carcinoma is its
      paramount objective. Fine-needle aspiration cytology can also establish a
      specific diagnosis for many lesions within this area. This technique can make
      specific diagnoses of angiofibroma, primary adenocarcinoma of the nasal sinuses,
      rhabdomyoma, granular cell tumor, and rhabdomyosarcoma. Each of these represents
      an important clinical entity with a specific therapy. Utilizing electron
      microscopy and immunohistochemical techniques, along with flow cytometry, can
      greatly broaden the diagnostic range and specificity of needle-aspiration
      cytology. Flow cytometry and immunohistochemistry are particularly useful in the
      establishment of monoclonality in lymphoproliferative processes and, hence, aid
      in the separation of reactive from lymphomatous lymphadenopathy.
      Immunohistochemistry can establish the precise nature of lesions as variable as
      rhabdomyosarcoma, olfactory neuroblastoma, and granular cell tumor. The prudent
      use of these techniques can be cost-effective and negate the need for more
      invasive diagnostic procedures. Needle-aspiration cytology represents a cost
      effective and rapid technique for the assessment of nodules and masses within the
      head and neck area. Limitations in accuracy exist. In particular, the separation
      of reactive atypia in benign squamous epithelium from well-differentiated
      squamous cell carcinoma may be exceedingly difficult, if not impossible.
      Nonetheless, the technique has a high degree of accuracy for the diagnosis of
      both primary and metastatic disease.

PMID- 9238366
TI  - Fine-needle aspiration of the lung.

PMID- 9238367
TI  - Fine-needle aspiration of soft tissue lesions.

PMID- 9238368
TI  - The factors important for successful fine-needle aspiration biopsies: a
      comparative study of breast diagnoses at two hospitals.

PMID- 9238370
TI  - Use of the standard 12-lead ECG to simulate electrode displacements.
AB  - Placement of the precordial electrodes for recording a 12-lead electrocardiogram
      (ECG) is subject to variation. Previous research has shown that displacement,
      especially in the longitudinal direction, can lead to changes in diagnosis. In
      practice, both the displacement and the effects of displacement on an individual
      ECG are unknown. To assess this effect for a given ECG, the authors developed a
      method to simulate ECGs at different displacements using only the recorded ECG.
      The material consisted of 746 body surface potential maps (BSPMs) containing 232
      cases without abnormalities, 277 with myocardial infarction (MI), and 237 with
      left ventricular hypertrophy. By interpolating BSPMs, ECGs from closely spaced
      electrode positions could be derived. Taking electrode positioning errors that
      may be encountered in practice, 40 ECGs at different electrode displacements
      (displaced ECGs) for each BSPM were derived. Using half of the BSPMs, for each
      displacement, a transformation matrix that transforms the ECG at the standard 12
      lead electrode positions (standard ECG) to the displaced ECG was determined.
      Using the other half of the BSPMs, each displaced ECG was compared with the ECG
      yielded by the corresponding transformation matrix (transformed ECG). For each
      comparison, the differences were assessed between the two sets of ECG signals and
      between the diagnostic computer classifications of the two sets. Signal
      differences were expressed as mean absolute amplitude differences over the QRS.
      Computer interpretation of MI and left ventricular hypertrophy was graded in five
      levels of certainty (no, consider, possible, probable, definite). For instance,
      for the largest longitudinal displacement studied of about one intercostal space,
      the 96th percentile mean absolute amplitude difference over the test set was 204
      microV. The percentage of cases showing a change in MI classification of more
      than two certainty levels was 2.7% for this displacement. When comparing the
      standard ECG with the displaced ECG, these figures were 434 microV and 8.3%,
      respectively. It is concluded that ECGs from displaced electrodes can be well
      simulated by transforming the standard ECG, both for the ECG signal and
      diagnostic classifications.

PMID- 9238369
TI  - New trends in computer ECG analysis.
AB  - Electrocardiographic (ECG) processing systems are operational in hospitals,
      outpatient clinics, primary care, and occupational medicine, and are used for
      population screening and epidemiologic studies. It appears that computer ECG
      analysis has been accepted, in spite of not yet performing quite as well as
      expert readers. The question is whether computerized ECG classification can be
      further improved. Possible new directions for research are: using information
      from all available beats, combining knowledge contained in different programs,
      incorporating knowledge gained in body surface mapping and modeling using
      information from non-ECG data, and collecting large ECG databases for the
      assessment of ECG programs. This article reviews these developments.

PMID- 9238371
TI  - Possibilities of using neural networks for ECG classification.
AB  - Some characteristics of the neural network approach have been tested and
      validated for the particular problem of diagnostic classification in the field of
      computerized electrocardiography. Two different databases have been used for the
      evaluation process: CORDA, developed by the Medical Informatics Department of the
      University of Leuven, and ECG-UCL, developed by the Cliniques Universitaires
      Saint-Luc, Universite Catholique de Louvain. Electrocardiographic signals
      classified on the basis of electrocardiographic independent clinical data, with a
      single diagnosis and no conduction abnormalities, have been considered. Seven
      diagnostic classes have been taken into account, including the different
      locations of ventricular hypertrophy and myocardial infarction. Two architectures
      of neural networks have been analyzed in detail considering three aspects: the
      normalization process, pruning techniques, and fuzzy preprocessing by the use of
      radial basis functions. The comparison of the results obtained with the two
      databases will be discussed in detail.

PMID- 9238372
TI  - Automatic learning of rules. A practical example of using artificial intelligence
      to improve computer-based detection of myocardial infarction and left ventricular
      hypertrophy in the 12-lead ECG.
AB  - The authors developed a computer program that detects myocardial infarction (MI)
      and left ventricular hypertrophy (LVH) in two steps: (1) by extracting parameter
      values from a 10-second, 12-lead electrocardiogram, and (2) by classifying the
      extracted parameter values with rule sets. Every disease has its dedicated set of
      rules. Hence, there are separate rule sets for anterior MI, inferior MI, and LVH.
      If at least one rule is satisfied, the disease is said to be detected. The
      computer program automatically develops these rule sets. A database (learning
      set) of healthy subjects and patients with MI, LVH, and mixed MI+LVH was used.
      After defining the rule type, initial limits, and expected quality of the rules
      (positive predictive value, minimum number of patients), the program creates a
      set of rules by varying the limits. The general rule type is defined as: disease
      = lim1l < p1 < or = lim1u and lim2l < p2 < or = lim2u and ... limnl < pn < or =
      limnu. When defining the rule types, only the parameters (p1 ... pn) that are
      known as clinical electrocardiographic criteria (amplitudes [mV] of Q, R, and T
      waves and ST-segment; duration [ms] of Q wave; frontal angle [degrees]) were
      used. This allowed for submitting the learned rule sets to an independent
      investigator for medical verification. It also allowed the creation of
      explanatory texts with the rules. These advantages are not offered by the neurons
      of a neural network. The learned rules were checked against a test set and the
      following results were obtained: MI: sensitivity 76.2%, positive predictive value
      98.6%; LVH: sensitivity 72.3%, positive predictive value 90.9%. The specificity
      ratings for MI are better than 98%; for LVH, better than 90%.

PMID- 9238373
TI  - Interactive and dynamic ECG analysis. Is it just an IDEA or a clinically relevant
      approach?
AB  - The idea that it is possible to increase the overall electrocardiographic (ECG)
      diagnostic performance is developed in this paper, provided that different
      programs or methods and various data sources are combined and that the dynamicity
      of the patients' record is considered. This dynamicity consists of the following
      three dimensions: beat-to-beat changes within continuous recordings, changes
      between serial records, and clinical events. Data integration should be time- or
      event-related, and multisources data should interact. Interactive and dynamic ECG
      analysis (IDEA), however, can only be achieved if powerful clinical workstations
      are developed that access the right information, when and where needed, a
      challenge that the IDEA workstation intends to accomplish.

PMID- 9238374
TI  - Automated serial ECG comparison based on the Minnesota code.
AB  - The Minnesota code was introduced in 1960, and since then, a number of computer
      programs have been written for classifying electrocardiograms according to the
      rules of the code. However, in 1982, extended rules for serial comparison based
      on the Minnesota code were published. This article presents the details of
      implementation of automated serial electrocardiographic comparison using the
      code. Its application in the West of Scotland Coronary Prevention Study, which
      was a double-blind trial of lipid lowering in 6.595 men, is also discussed.

PMID- 9238375
TI  - Development of a new approach to serial analysis. The manufacturer's viewpoint.
AB  - The Megacare Electrocardiographic (ECG) Management System (Siemens-Elema,
      Stockholm, Sweden) incorporates methods for serial comparison of the 12-lead ECG
      based on the Glasgow interpretation program. While a computer is obviously useful
      for reporting serial changes following myocardial infarction, it was believed
      helpful to produce a summary serial comparison statement that would take into
      account the fact that ECG appearances may normally fluctuate from day to day for
      a variety of reasons. Thus, five additional summary statements were added to the
      Glasgow program to indicate the extent of change globally compared to the
      previous ECG recording. In an ECG management system, an important facility that
      can potentially cause difficulties with serial comparison is overreading. When a
      statement has been altered by a reviewer, the changes are required to be
      incorporated into the ECG file so that in any subsequent serial comparison, the
      modified report is available for comparison with the next ECG. The Megacare
      system allows for this, and its methodology is described in this article.

PMID- 9238376
TI  - Techniques for improving overall consistency of serial ECG analysis.
AB  - The techniques that improve the overall repeatability of computer interpretation
      of electrocardiograms (ECGs) that have been recorded several minutes apart from
      patients in a clinically stable condition are described. Estimates of the normal
      amounts of variability present in many ECG parameters that are used in the
      identification of a variety of cardiac abnormalities have been adopted in
      conjunction with smoothing techniques to form the basis of the new methodology.
      When applied to the Glasgow ECG analysis program, these new methods improve
      overall repeatability by about 31% when tested on a set of 263 pairs of ECGs.
      Randomly generated noise was added to the test set and an additional technique
      aimed at removing noise from the ECG tracings was used in conjunction with the
      smoothing methods. The observed improvement over the original repeatability was
      63%.

PMID- 9238377
TI  - Exercise recordings for the detection of T wave alternans. Promises and pitfalls.
AB  - Despite significant advances in the treatment of sudden cardiac death, many
      individuals still go untreated because routine clinical tests do not identify
      them to be at risk. Recently, a study to identify individuals at risk has shown
      that the presence of T wave alternans (TWA), a fluctuation in T wave morphology
      occurring on an every-other-beat basis, is an accurate predictor of subsequent
      ventricular tachyarrhythmic events. T wave alternans as low as a few microvolts
      was found to be significant in predicting risk. Since TWA is often detectable
      only at elevated heart rates, the study used atrial pacing to increase the heart
      rate to approximately 100 beats/min. To make TWA measurement more broadly
      applicable, the authors have developed a methodology that uses noninvasive
      physiologic stress to raise the heart rate. A particular challenge was the
      measurement of TWA during exercise, since the levels of noise during exercise can
      far exceed the levels of TWA. However, by using special multisegment Hi-Res
      electrodes (Cambridge Heart, Bedford, MA), noise reduction software, and a
      spectral method of alternans analysis, the authors have been able to reduce noise
      and reliably measure microvolt-level alternans. This study presents an overview
      of the methodology for recording and analyzing microvolt-level TWA during
      ergometer exercise.

PMID- 9238378
TI  - Are serial Holter QT, late potential, and wavelet measurement clinically useful?
AB  - Clinical centers are increasingly using new techniques such as Holter QT, late
      potential, and wavelet measurements. However, we lack validated databases for the
      assessment of the performance of the signal-processing methods and their
      reproducibility. Failure of the QT interval to adapt to changes in the heart rate
      is considered to be a more meaningful parameter than QT prolongation itself. In
      this study, different factors that may affect the reproducibility of QT and QTm
      (onset of the QRS to the maximum of T) measurement are analyzed: the incidence of
      sympathetic tone and parasympathetic activity on low- and high-frequency QT
      variability, the very low frequency dependency of the QT interval to changes in
      the R-R interval, changes in the heart's position, and measurement errors.
      Typical root-mean-square values of the beat-to-beat measurement errors in upright
      position Holter recordings are only 1.5 ms for QT versus 3.4 ms for QTm. Although
      the dependence of the QT interval on the heart rate is well established, the
      method for rate correction of the QT interval remains controversial. None of the
      formulas for heart rate adjustment of the QT previously proposed provide complete
      correction for all of the rate influences involved due to "memory phenomenon";
      that is, there is a time delay, ranging up to 3-4 minutes, between a change in
      heart rate and the subsequent change in the QT interval. This problem has been
      solved by developing patient-specific neural networks that are trained to
      "identify" the dynamic behavior of the QT interval (or QTm) as a function of the
      R-R interval in order to predict the beat-to-beat changes of the QT interval as a
      function of the measured beat-to-beat changes of the R-R interval. Computing the
      differences between the predicted and the measured QT interval will allow for the
      detection of any significant deviations, both in the steady-state and transient
      conditions. Recent developments in the analysis of the high-resolution
      electrocardiogram (HRECG) in the time domain and frequency domain, with emphasis
      on the assessment of the reproducibility of late potential and wavelet
      measurements, are also reported in this study. The two main causes of variability
      in HRECG analysis are physiology and, for time-domain analysis, intermanufacturer
      variability. Physiologic changes can be overcome by standardizing the clinical
      protocols and repeating the recordings. The most important technical requirement
      for the proper use of late potentials is to standardize the algorithm for the
      detection of QRS offset among different late potential analyzing machines so that
      clinical data can be exchanged. The recently introduced wavelet transform
      provides a fruitful alternative to the more classical time-domain methods.
      Preliminary results show an 8 to 15% performance improvement over conventional
      time-domain analysis for the stratification of the HRECG after myocardial
      infarction. Reproducibility is excellent, up to 100%, but needs to be assessed on
      larger populations matched for age, sex, and pathology.

PMID- 9238379
TI  - Analysis of interval measurements on CSE multilead reference ECGs.
AB  - As part of the International Electrotechnical Commission's (IEC) efforts to
      develop standards for interpretive electrocardiographs, electrocardiograms (ECGs)
      of the Common Standards of Electrocardiography (CSE) multilead measurement
      database were processed to (1) determine whether original ECG data would offer
      any advantage over cycle-repeated (artificial) ECGs and (2) compare the "clean"
      ECGs selected for interval measurement compliance testing (n = 100) with the
      remaining 25 "noisy" or nonsinus rhythm ECGs. Two sets of CSE measurement ECGs,
      namely, 125 original ECGs of the MO1 series and 125 artificial ECGs of the MA1
      series were divided into 100 IEC-selected clean ECGs with good P and T waves and
      25 noisy or nonsinus ECGs and processed for global wave duration and interval
      measurements (P duration, PR interval, QRS duration, and QT interval). The
      measured duration and interval values were compared against the CSE reference
      values (medians of referee values for 25 physician overread ECGs and medians of
      interpretive programs for the rest) to compute the measurement "differences".
      Also, the data of the median cardiac complex were evaluated for noise content.
      The original ECG data gave consistently smaller differences for all of the four
      measurements than the differences with the artificial ECG data. The noise levels
      in the median complexes formed from the original ECG data were significantly
      lower than the noise levels in the median complexes from the artificial ECG data.
      The noise levels in the medians of the 100 clean ECGs were lower than the noise
      levels in the medians of the 25 noisy ECGs for both the original and artificial
      ECG data.

PMID- 9238380
TI  - Influence of ECG measurement accuracy on ECG diagnostic statements.
AB  - Computer analysis of electrocardiograms (ECGs) provides a large amount of ECG
      measurement data, which may be used for diagnostic classification and storage in
      ECG databases. Until now, neither error limits for ECG measurements have been
      specified nor has their influence on diagnostic statements been systematically
      investigated. An analytical method is presented to estimate the influence of
      measurement errors on the accuracy of diagnostic ECG statements. Systematic
      (offset) errors will usually result in an increase of false positive or false
      negative statements since they cause a shift of the working point on the receiver
      operating characteristics curve. Measurement error dispersion broadens the
      distribution function of discriminative measurement parameters and, therefore,
      usually increases the overlap between discriminative parameters. This results in
      a flattening of the receiver operating characteristics curve and an increase of
      false positive and false negative classifications. The method developed has been
      applied to ECG conduction defect diagnoses by using the proposed International
      Electrotechnical Commission's interval measurement tolerance limits. These limits
      appear too large because more than 30% of false positive atrial conduction defect
      statements and 10-18% of false intraventricular conduction defect statements
      could be expected due to tolerated measurement errors. To assure long-term
      usability of ECG measurement databases, it is recommended that systems provide
      its error tolerance limits obtained on a defined test set.

PMID- 9238381
TI  - Comparison of 12-lead repolarization parameters during follow-up study in middle
      aged sportsmen and in patients during acute myocardial infarction.
AB  - Consecutive electrocardiographic (ECG) analysis is very useful in acute coronary
      ischemia, but it is known that ECG patterns can be misleading in subjects with
      left ventricular hypertrophy, mainly during the repolarization phase. An
      automated system was developed to collect, store, and follow-up all heterogeneous
      data concerning a cohort of 1,898 subjects (1,039 men), 45-65 years old, 50% of
      whom were physically active. The reliability of several ECG markers of ischemia
      was tested during chronic follow-up study (1993-1995) in 23 healthy sedentary men
      without hypertension (group 1) recorded in our database, as well as in 9 subjects
      performing regular sporting activity (SA) (group 2). The same parameters were
      evaluated in the intensive care unit in nine patients affected by coronary artery
      disease, during either successful or unsuccessful thrombolytic therapy of acute
      myocardial infarction (AMI) (group 3). Twelve-lead ECGs were recorded, analyzed
      by the Hannover ECG system program, compressed, and stored according to the
      Standard Communication Protocol in each of the three groups. The changes in ST
      amplitude 20, 60, and 80 ms alter the J point were very small in each subject of
      groups 1 and 2, while upsloping from 1 to 10 mm in several leads was observed
      slowly, rapidly, or intermittently in group 3 patients during ischemia. The ST
      slope and the concordance of the T wave and ST amplitude were helpful in
      differentiating normal and SA subjects from AMI patients. These results, obtained
      in resting conditions, underline that the difference among ST-T abnormalities in
      subjects with left ventricular hypertrophy due to SA are consistently different
      from those observed in patients with AMI. The serial digital ECG can be helpful
      to underline these differences.

PMID- 9238382
TI  - Computer versus manual measurement of ST-segment deviation.
AB  - Total ST scores (sum of absolute deviations in all 12 electrocardiographic [ECG]
      leads) have been used for research purposes to estimate total ischemic burden and
      to predict reperfusion after thrombolytic therapy. Computerized monitoring
      systems are capable of measuring ST deviation to the 10-microV level, whereas
      humans are incapable of such precise resolution. The purpose of this study was to
      compare computer versus manual ST scores in 12-lead ECGs exhibiting ischemia and
      to compare interrater reliability of manual measurements between two experts. A
      total of 58 subjects with 100 microV or more ST deviation in one or more leads
      during percutaneous transluminal coronary angioplasty balloon inflation were
      selected for analysis. ST measurements were made at J + 80 ms, using the
      isoelectric line as a reference, and summed across all 12 leads. Manual
      measurements were made to a minimum of 50 microV by two independent reviewers
      blinded to the computer scores. Total ST scores were compared using paired t
      tests, and Pearson coefficients were used to test the correlations. A high
      correlation was observed between the manual and computer measurements (r = .96, P
      < .00) and between the two reviewers (r = .96, P < .00). A high degree of
      interrater reliability is possible with manual measurements of ST deviation.
      Computer measurements are consistently greater than manual measurements,
      presumably because humans "round down" to the nearest 50 microV. As such,
      computers may detect ischemia that is missed by humans. However, computer and
      manual measurements of ST deviation should not be mixed when used as a variable
      for research.

PMID- 9238383
TI  - Validation of a new computer program for Minnesota coding.
AB  - The Minnesota code (MC) is a classification system for electrocardiograms (ECGs)
      that is used for ECG coding in epidemiologic studies. As the MC measurement
      procedures and rules are complex, visual coding is time-consuming and error
      prone. Automation should reduce measurement and coding errors. The authors
      developed an MC program, closely adhering to the MC regulations. To validate the
      program, a test set of 300 ECGs containing a wide variety of codable patterns was
      collected. The ECGs were coded independently by the program and by an experienced
      human reader. A reference code ("truth") was established by resolving
      disagreements through a consensus procedure. If the computer and human agreed,
      they were considered to be correct. Sensitivity and specificity were computed for
      each of the nine main code categories of the MC, both for the computer and for
      visual coding. The results show that the program is as good as or better than the
      human reader for sensitivity and specificity of all MC categories. Particularly
      noteworthy is the good program performance for arrhythmia coding. Most coding
      differences between the program and truth arise from small, borderline
      measurement differences in combination with the all-or-none character of the
      coding criteria. In conclusion, computerized Minnesota coding is a valuable
      alternative or supplement to visual coding.

PMID- 9238384
TI  - Dispersion of ventricular repolarization in hypertrophic cardiomyopathy.
AB  - On an averaged QRS-T cycle from a 15-lead record (12-lead electrocardiogram + XYZ
      leads) and through interactive editing, four electrocardiographic indices of the
      dispersion of ventricular repolarization (DVR) are automatically computed and
      represent the maximal interlead difference of QT and JTend and QT and JTapex. The
      values of these indices were then examined in three clinical groups matched for
      age and sex: normal subjects (control), patients with left ventricular
      hypertrophy (LVH group), and patients with hypertrophic cardiomyopathy (HCM
      group) without ventricular arrhythmias and without interacting drugs. The mean
      values of all four DVR indices were significantly increased in the HCM group
      compared with the control group and the LVH group of another origin (ie, for the
      QTe dispersion index, the mean values and the 97.5th percentiles were,
      respectively, 65 +/- 18 ms and 97 ms in the HCM group, 41 +/- 25 ms and 79 ms in
      the LVH group, and 31 +/- 15 ms and 58 ms in the control group). The maximal QT
      interval was also significantly longer in the HCM group (464 +/- 30 ms) than in
      the LVH group (436 +/- 32 ms) and the control group (428 +/- 25 ms).

PMID- 9238386
TI  - The role of atrial anatomy in clinical atrial arrhythmias.

PMID- 9238385
TI  - ECG waveforms and cardiac electric sources.

PMID- 9238387
TI  - Temporal and spatial analysis of potential maps via multiresolution
      decompositions.
AB  - Cardiac potentials recorded on the epicardium or the body surface by an array of
      electrodes are usually analyzed either as spatial distributions or temporal
      waveforms. Thus, the analysis often involves temporal descriptors (eg. max dV/dt)
      or spatial descriptors (eg. location of local extrema) only. The best known
      transform technique that has been applied to these data that combines both
      spatial and temporal characteristics is the Karhunen-Loeve transform, a global
      transform applied to temporal and/or spatial bases obtained by statistical
      analysis of a database. As an alternative, multiresolution decompositions and
      related wavelet-type transforms have recently seen great development in signal
      processing and related fields. They offer flexibility, employing transformations
      onto local (rather than global) and fixed (rather than data-dependent) databases,
      and allow transformation of distributions, waveforms, or both, as desired. The
      utility of this method as applied to temporal and spatial segmentation and
      analysis of map data from both epicardial plaques and body surface potentials
      recorded during percutaneous transluminal coronary angioplasty is illustrated.

PMID- 9238388
TI  - Intracardiac electrogram transformation. Morphometric implications for
      implantable devices.

PMID- 9238389
TI  - Measuring spatial waves of repolarization in canine ventricles using high
      resolution epicardial mapping.
AB  - The importance of the role of ventricular repolarization in arrhythmogenesis and
      defibrillation prompted the exploration of new methods for observing and
      measuring repolarization. Specifically, the authors' goal was to establish
      independent procedures for assessing activation-recovery intervals. Canine
      epicardial electrograms from high-resolution arrays (2-mm spacing, 25 x 21
      electrodes) were recorded-during pacing from a variety of single or
      simultaneously paced epicardial locations in canine hearts. For each activation
      sequence, the activation and repolarization times were measured using timing of
      intrinsic QRS and T wave deflections (activation-recovery interval method) and
      timing of the peak magnitude of spatial derivatives (gradient method). Both
      methods should, theoretically, provide estimates of local activation and
      repolarization times, which reflect timing of local action potential upstrokes
      and downstrokes. Scattergrams comparing activation and recovery times for the two
      methods showed high correlation, slopes close to 1.0, and intercepts near the
      origin. For most activation sequences, observation of the potential and gradient
      distributions as dynamic, three-dimensional perspective displays, revealed a well
      defined, rapidly propagating repolarization wave, superimposed on a slowly
      varying, high-amplitude distribution occurring during the T wave. These data
      suggest that repolarization times measured using temporal or spatial derivatives
      are consistent with theoretical predictions and reflect timing of local action
      potential downstrokes. They also suggest potential utility of combining spatial
      and temporal approaches for improving reliability in the measurements.

PMID- 9238390
TI  - Asymptomatic coronary artery disease detection: update 1996. A screening protocol
      using 16-lead high-resolution ECG, ultrafast CT, exercise testing, and
      radionuclear imaging.
AB  - The authors have proposed a new four-step screening algorithm to detect
      asymptomatic coronary artery disease (CAD) in flight school candidates, cadets,
      and rated flyers of the Unites States Air Force (USAF). In step 1, the USAF
      Armstrong Laboratory (USAF/AL) risk profile and improved 16-lead high-resolution
      electrocardiogram/vectorcardiogram will be recorded at baseline. On routine
      follow-up evaluations, quantitative serial comparisons will be performed by the
      method of Kornreich. In step 2, beginning with flight school candidates and
      cadets, all three groups will be studied by the ultrafast computed tomograph (CT)
      protocol. Those candidates positive for coronary calcium will be studied by
      coronary angiography and ventriculography, and their eligibility for continued
      rated flight status will be determined by present criteria. In step 3, those
      candidates negative for coronary calcium by ultrafast CT will then be screened by
      the newly defined and improved high-sensitivity treadmill exercise test criteria.
      In step 4, candidates with a positive treadmill exercise test result, or who are
      also found in the upper quintile of the USAF/AL risk profile, wild also have
      exercise nuclear wall motion studies and perfusion scans. If these are abnormal
      and suggestive of myocardial ischemia, this subset will also be studied by heart
      catheterization and coronary angiography, and their eligibility for continued
      rated flight status will be determined by present criteria. The incidence of
      coronary calcium/no calcium for each degree of stenosis in the 6,000 flyers in
      each quintile was used to develop the following projections: (1) that more than 3
      of 4 rated flyers with unsuspected CAD, and (2) more than 9 of 10 with severe
      flow-limiting CAD can be identified by these upgraded screening procedures.
      Evidence is herein presented that these enhancements will result in a major (5-8
      fold) increase in case finding of this disease. Based on the estimate of four
      lost high-performance aircrafts per year from sudden incapacitation of the pilot
      due to CAD, when this four-step screen is fully operational, it can be expected
      to reduce the $80 million annual losses to the United States government from CAD
      by 85%, a savings of $68 million per year.

PMID- 9238391
TI  - Evaluation of novel measurement methods for detecting heterogeneous
      repolarization.
AB  - There exists a well-documented link between heterogeneity of cardiac recovery
      characteristics and vulnerability to arrhythmia; however, electrocardiographic
      detection of this heterogeneity remains problematic. The only modalities suitable
      for measuring variation of repolarization are electrophysiologic in nature, with
      action potential duration in single cells the most direct method and QT intervals
      from the body surface electrocardiogram the most common clinical approach. The
      authors have shown previously, however, that the QT interval is a poor measure of
      regional change in repolarization, especially when shortening occurs. Here, the
      authors discuss an experimental preparation based on an isolated canine heart
      suspended in a human-shaped, instrumented, electrolytic tank and describe a
      method of applying cold to create local, transient changes in recovery
      characteristics. The authors have simultaneously recorded epicardial and torso
      tank surface potentials before, during, and after intervention, and from them
      have generated isopotential and isointegral maps and computed activation-recovery
      intervals (ARIs). In all cases, epicardial potentials revealed changes in
      recovery associated with localized heating and cooling. The changes were visible
      from tank surface potential distributions in some, but not all, cases. The
      results also suggest that epicardial ARIs are sensitive to changes in recovery
      and that, at least for a subset of tank surface leads, ARIs can be used to create
      noninvasive indices of disparity of repolarization characteristics.

PMID- 9238392
TI  - Familial and genetic influences on heart rate variability.
AB  - The authors tested the hypothesis of a genetic influence on heart rate
      variability (HRV). This genetic influence was assessed in 62, twin pairs (30
      monozygotic, 32 dizygotic). From all twins, long-term electrocardiographic
      records were obtained, edited, and analyzed. Heart rate variability analysis was
      performed on the basis of parameters from time-domain, frequency-domain, and
      nonlinear dynamics. First, the parameter distances between the two twins of a
      pair and between one of the two and a third randomly selected person of another
      age-matched twin pair (ST1) were compared. Second, the parameter distances
      between the two twins and the averaged parameter distances of these two twins to
      all other age-matched persons (ST2) were compared. Finally, the averaged
      differences in parameter values between monozygotic and dizygotic age-matched
      twin pairs were compared. For statistical analysis, the nonparametric Wilcoxon's
      matched-pair signed rank test and parametric t-test for paired samples were used.
      Twin pairs show a significant lower difference in parameter values than other
      randomly selected and age-matched couples (P < .001 in ST1 and ST2). This
      reflects a considerable familial influence. Most parameters of the time-domain,
      none of the frequency-domain, and half of the nonlinear dynamics show significant
      differences between twin pairs and nontwin pairs. As a result of the comparison
      between monozygotic and dizygotic twin pairs, a significant lower parameter
      difference in the monozygotic pairs (P < .05) is found. These results suggest
      that there is a genetic component in heart rate generation and HRV, in addition
      to family environmental influences. Analysis of HRV might become a useful method
      in phenotyping severe genetic changes in cardiovascular diseases.

PMID- 9238393
TI  - Ventricular tachycardia versus ventricular fibrillation. Discrimination by
      current antitachycardia devices.

PMID- 9238394
TI  - Heart rate variability in patients with mild heart failure due to coronary artery
      disease. Comparison of patients with and without prior myocardial infarction.

PMID- 9238395
TI  - Comparison of high-resolution and standard ECG parameters of myocardial ischemia
      during PTCA.

PMID- 9238396
TI  - R wave amplitude in ischemia, injury, and infarction. Plenary address.

PMID- 9238397
TI  - Stratification of time-frequency abnormalities in the signal-averaged high
      resolution ECG in postinfarction patients with and without ventricular
      tachycardia and congenital long QT syndrome.
AB  - Having developed sound mathematical techniques that allow precise mapping of
      cardiac signals in the time-frequency (TF) and time-scale planes, the next
      important issue is to extract from these representations information that best
      reflects the electrophysiologic and anatomic derangement unique to patients at
      risk of arrhythmias and other cardiac diseases. In this study, the authors
      present a new method that stratifies the magnitude of the TF transforms of
      abnormal cardiac signals into distinguishing features by comparing the means of
      the coefficients of the TF transforms of any study population to the
      corresponding means of a control population using a standard ANOVA technique.
      This results in a three-dimensional mapping of the high-resolution ECG into time,
      frequency, and P value components. Significant energy increases are given
      positive P values and depressed energies are given negative P values: these are
      ranked according to a color scale. The method was tested on two study
      populations: postmyocardial infarction patients with documented ventricular
      tachycardia (MI+VT, n = 23) and without (MI-VT, n = 40) and patients with
      congenital long QT syndrome (LQTS, n = 19). Two groups of healthy control
      subjects (n = 31 and n = 40) were used as a reference group matched for sex. The
      study results were based on the Morlet analyzing wavelets, with frequencies
      ranging from 40 to 250 Hz in 10 logarithmically progressing scales, and computed
      millisecond per millisecond over a 350-ms analyzing time window, starting from
      100 ms before the onset of the QRS. The patients with MI+VT displayed
      significantly increased high-frequency components in the 40-250-Hz frequency
      range, corresponding to prolonged QRS duration and late potentials in the area
      from 80 to 150 ms after QRS onset. Significantly depressed energy (P < 10(-4))
      was also observed for the 40-106-Hz frequency range in the first 50 ms of the QRS
      complex, mainly in lead Y and in the magnitude vector. In patients with LQTS,
      significant modifications (P < 10(-2)) were observed in the first half of the QRS
      and in the ST-segment, in all leads, revealing anomalies in the genesis of the
      ventricular depolarization and repolarization processes. In conclusion, the
      authors propose a new method for the stratification of abnormal TF components
      occurring in the signal-averaged high-resolution electrocardiogram of patients at
      risk of VT and fibrillation under different pathologic conditions.

PMID- 9238398
TI  - Defibrillation success is associated with myocardial organization. Spatial
      coherence as a new method of quantifying the electrical organization of the
      heart.
AB  - The relationship between the degree of electrical organization of ventricular
      fibrillation (VF) and defibrillation success was investigated in this study using
      a new technique to quantify organization--spatial coherence. This technique
      employs the use of the magnitude-squared coherence spectrum to analyze
      multichannel electrograms obtained during a cardiac mapping study. Magnitude
      squared coherence values for all possible pairs of electrograms recorded from an
      epicardial plaque consisting of 112 electrodes were computed. Average coherence
      was plotted versus electrode separation distance, and the data were fit with an
      exponentially decaying curve. Two parameters indicative of myocardial
      organization were extracted from the curve. The coherence length (d) was defined
      as the distance (mm) at which the average coherence dropped to a given level, and
      the coherence strength was defined as the average coherence value at a given
      distance. Higher values for these parameters were hypothesized to indicate higher
      levels of organization. The spatial coherence technique was tested previously in
      a canine study of ventricular fibrillation (VF) and normal sinus rhythm, and the
      results suggested that spatial coherence parameters may be used to compare
      cardiac rhythms in terms of their organization. To test the hypothesis that
      organization is related to defibrillation success, 164 mapping sessions recorded
      during repeated VF induction and defibrillation trials using a monophasic
      waveform were performed in a close-chested canine study (n = 9) using a fixed
      energy and VF duration (10 seconds). Three coherence lengths and five coherence
      strengths were calculated for each VF episode. Results using a two-way analysis
      of variance with blocking between dogs showed that all of the coherence length
      and three of the coherence strength parameters were higher for those VF episodes
      that were successfully defibrillated than for those that were not (P < .05).
      Energy delivered and transmyocardial impedance were not significantly different
      between the groups. The authors conclude (1) the organization of a VF episode, as
      reflected in the spatial coherence parameters, is related to defibrillation
      success and may be partially responsible for the probabilistic nature of
      defibrillation and (2) the spatial coherence technique provides a means of
      quantifying myocardial electrical organization and is an important experimental
      tool that may be used to obtain a better understanding of VF and its termination.

PMID- 9238399
TI  - A:V = 1:1 cardiac arrhythmia detection by VA interval analysis.
AB  - Dual-chamber-sensing implantable-cardioverter defibrillators are soon expected to
      replace ventricular sensing devices. The addition of an atrial sensing lead will
      dramatically improve the specificity of arrhythmia detection. Even when using
      combined ventricular and atrial rate criteria, ambiguity in the case of atrial
      tachycardia with: anterograde conduction versus ventricular tachycardia with:
      retrograde conduction still remains. The introduction of dual-chamber sensing in
      antitachycardia devices allows for additional features, such as the measurement
      of atrioventricular (AV) and ventriculoatrial (VA) intervals. This study
      investigated relationships between AV and VA intervals to address problems
      arising in tachycardias with confounding 1:1 relationships. Thirty-one passages
      of 1:1 anterograde conduction from nine patients during atrial pacing at cycle
      lengths of 600-300 ms and 24 passages of 1:1 retrograde conduction from eight
      patients during ventricular pacing at cycle lengths of 600-300 ms were analyzed.
      Moving averages of three successive VA interval measurements were used to develop
      a criterion to be implemented into an algorithm to reduce ambiguity. Five
      randomly selected ventricular pacing passages were used as a training set. Upper
      and lower VA interval boundaries (234 ms and 132 ms) determined from the training
      set were used to classify 1:1 retrograde activation. To account for premature
      beats and outliers, the boundary criterion required 9 of 12 of the most recent
      moving averages to fall within the upper and lower limits. Of the 19 analyzed
      passages of ventricular pacing, 18 (95%) were correctly classified using the VA
      interval as an added feature. Of the 31 atrial pacing passages, 24 (77%) were
      correctly classified. Using only atrial or ventricular rates, all 1:1
      tachycardias in this patient sample would be classified as ventricular
      tachycardia, resulting in false shocks. Specificity of diagnosis in ambiguous 1:1
      tachycardias can be increased using VA interval measurements at the cost of
      minimum loss in sensitivity for ventricular tachycardia detection. This algorithm
      imposes little in additional computation for dual-chamber-sensing implantable
      cardioverter defibrillators and greatly reduces the possibility of false shocks
      in 1:1 supraventricular tachycardias.

PMID- 9238400
TI  - Automated analysis of intracardiac electrograms obtained during extrastimulus
      tests using a three-dimensional electrophysiology model.
AB  - Catheter ablation procedures are performed by highly trained and experienced
      cardiology subspecialists. Yet the massive amount of data produced during these
      procedures creates a data overload problem that can impede the performance of
      even the best practitioners. This may be evidenced by (1) overlooking important
      signal features, (2) misinterpreting the signals, and (3) misinterpreting
      catheter locations in the heart, all of which can lead to increased procedure
      duration, applications of radiofrequency energy to the wrong part of the heart,
      or both. This article presents the first results from a project aimed at
      developing a model-based system for interpreting intracardiac electrograms in
      near real time. The system is intended to assist physicians in interpreting the
      enormous amounts of data recorded during catheter ablation studies. It is an
      extension of the Einthoven system that has been extended to account for the three
      dimensional relationships in the cardiac conduction system as recorded in the
      various intracardiac electrograms. The new three-dimensional cardiac conduction
      model and the enhancements to Einthoven's reasoning algorithms are presented. The
      locus of this study is on interpreting the results of ventricular extrastimulus
      tests. Data collected for this study and the output generated by the system are
      presented.

PMID- 9238401
TI  - Heart rate control in infants at risk.

PMID- 9238402
TI  - Postnatal maturation of autonomic modulation of heart rate. Assessments of
      parasympathetic and sympathetic efferent function in the developing canine heart.

PMID- 9238403
TI  - Implantable cardioverter-defibrillators in children. A perspective on current and
      future uses.

PMID- 9238404
TI  - Similar recovery properties in fast and slow atrioventricular nodal pathways.

PMID- 9238406
TI  - High-density endocardial activation mapping of the right atrium in three
      dimensions by composition of multielectrode catheter recordings.
AB  - The use of radiofrequency ablation for treatment of complex arrhythmia substrates
      has prompted interest in transcatheter endocardial activation mapping. Technical
      constraints on catheter fabrication and the intention to use such maps to guide
      ablation both demand innovative approaches to mapping. A fluoroscopically based
      endocardial mapping technique is proposed to improve the ability of
      electrophysiologists to interpret large amounts of data acquired using
      multielectrode catheter arrays, improving their ability to visualize the data and
      act on its content. This technique addresses previous limitations imposed by the
      number of electrodes that can be deployed and by the difficulty in determining
      their relative spatial locations. It is based on the composition of multiple
      activation sequence mappings made in a single rhythm, with the spatial locations
      of recording electrode pairs determined in orthogonal fluoroscopic views
      referenced to stable intrathoracic markers. Rather than imposing a geometry
      determined primarily by the measurement apparatus, the spatial locations of only
      those electrodes in proximity to the endocardial surface, as determined by their
      ability to record bipolar electrograms, are measured. In this manner, the
      geometry of the endocardium may be approximated by measurements made of electrode
      position. Using this approach, the number of endocardial sites that can be
      sampled in a stable rhythm is theoretically unlimited, resulting in the
      realization of high-resolution activation maps. Spatiotemporal data may be used
      to create three-dimensional activation sequence maps, displayed as animated
      sequences. This technique was used in anatomically normal and diseased human
      right atria to create activation maps of sinus and paced rhythms, classic atrial
      flutter, and postoperative intraatrial reentrant tachycardia, using a median of
      108 electrode positions (range, 27-197) in 25 maps. The activation sequences
      represented by these maps were diverse, but qualitatively concordant with known
      mechanisms of atrial activation. High-density catheter-based activation mapping
      of the right atrium is feasible and may improve understanding of complex
      arrhythmias and assist in the development of ablative techniques. Further
      research is needed on the spatial correlation between cardiac anatomy and
      fluorography, suppression of spatial artifact, and optimal mapping densities.

PMID- 9238405
TI  - Use of the His/RVA electrode catheter in children.
AB  - Comprehensive electrophysiologic study with radiofrequency ablation requires a
      number of intracardiac catheters. To reduce the number of catheters placed in
      children, the authors evaluated a series of customized catheters that combined
      the functions of two catheters. The customized 6F catheter contains eight
      electrodes placed in pairs at 4, 5, 6, 7, or 8 cm from the tip for recording the
      His electrogram and at the tip for right ventricular pacing. The amplitude of the
      bundle of His potential recorded through the His right ventricular apex (RVA)
      catheter (n = 63) and the ventricular pacing threshold (in mA) (n = 48) were
      measured and compared to the maximal bundle of His potential recorded with a 6F
      hexapolar catheter in 24 and 13 other patients, respectively. The relationship
      between the distance from the distal electrode pair at the tip and the third
      electrode from the tip (the His/RVA distance) and patient size was analyzed in 42
      patients. Following the initial study in the 90 patients, the selection of the
      optimal His/RVA catheter for 19 patients was determined by examining the
      regression plots derived from the first group of 90 patients. The measured
      His/RVA distance was then determined by noting the His/RVA distance of the
      catheter used. Regression analysis was then used to evaluate the fit between the
      predicted His/RVA distance based on weight, height, or body surface area (BSA)
      and the observed His/RVA distance. The maximal bundle of His electrogram measured
      in the two groups using the His/RVA catheter was compared. To evaluate catheter
      stability during the study, the amplitude of the maximal His potential was
      measured in the 19 patients at the onset, midpoint, and end of the study. The
      maximal His potential recorded through the octapolar catheter (0.21 mV) was
      significantly (P < .04) greater than that recorded through the hexapolar catheter
      (0.10 mV). The mean ventricular threshold measured through the octapolar catheter
      (0.44 mA) was significantly (P < .001) less than that measured through the
      hexapolar catheter (1.13 mA). There was a significant (P < .0001) correlation
      between BSA, weight, and height and the His/RVA distance. There was no
      significant difference in the mean maximal amplitude of the His potential (0.21
      +/- 0.31 mV vs 0.15 +/- 0.12 mV) recorded through the His/RVA catheter between
      the two groups. The His/RVA distance estimated by weight, when plotted against
      the measured distance, demonstrated a good correlation (r = .84) between the
      expected His/RVA distance based on the subject's weight and that actually
      observed. In 18 of 19 subjects, the first catheter based on the patient's weight
      (in kilograms) predicted the appropriate and only catheter used. There was no
      significant difference in the mean maximal bundle of His electrogram recorded at
      the beginning of the study (0.15 +/- 0.12 mV), midway into the study (0.15 +/-
      0.11 mV), and at the end (0.13 +/- 0.13 mV); however, there was extensive
      variation within individuals and over time. These data support the recording of a
      stable, high-quality bundle of His electrogram and RVA pacing through a single
      catheter system and, hence, have important, practical implications for invasive
      electrophysiologic studies in children.

PMID- 9238407
TI  - Adjustment of ECG left ventricular hypertrophy criteria for body mass index and
      age improves classification accuracy. The effects of hypertension and obesity.
AB  - Population-based data from the Framingham Heart Study have served as the basis
      for adjusting electrocardiographic (ECG) criteria for echocardiographically
      determined left ventricular hypertrophy (LVH) for two determinants of their
      sensitivity: body mass index and age. Estimated regression equations that predict
      echo-derived left ventricular mass from an ECG LVH voltage criterion, body mass
      index, and age, for 1,468 men and 1,883 women, provide a simple and effective
      means of adjusting that criterion for these variables. The authors evaluated five
      different ECG LVH criteria, comparing the performances of their original and
      adjusted versions within this database. All adjusted criteria significantly
      outperformed their unadjusted counterparts. Of these five criteria, the Cornell
      voltage duration product, (RAVL + SV3). QRS interval, exhibited the greatest
      sensitivity at all levels of specificity for both sexes (39 and 51% sensitivity
      at 95% specificity in men and women, respectively). Its performance was further
      evaluated with separate adjustment algorithms developed for lean versus obese and
      normotensive versus hypertensive men and women. Age and body mass index
      adjustment produced significant improvements for both lean and obese women and
      for obese men. A marginal gain in sensitivity was found in lean normotensive men.
      Within the relatively small subgroup of lean hypertensive men, no improvement was
      observed. These results suggest that among Caucasian adults, the Cornell voltage
      duration product adjusted for body mass index and age offers significant
      improvement for the detection of echocardiographically determined LVH in all but
      lean men; within the latter group, it loses no sensitivity in comparison with the
      original criterion.

PMID- 9238408
TI  - Is the echocardiogram an appropriate ECG validity standard for the detection and
      change in left ventricular size?
AB  - The echocardiogram (Echo) is the validity standard for left ventricular mass
      (LVM) and LV hypertrophy (LVH). Numerous studies have confirmed modest
      correlations between the electrocardiogram (ECG) and Echo for LVM and low ECG
      sensitivity for Echo-LVH. In spite of this, investigators continue modeling ECG
      parameters to optimize their relation with the Echo. The authors studied the
      association between eight ECG criteria and Echo-LVM estimates in a biracial
      population of men and women with mild hypertension. The Echo-LVM was determined
      by the Penn convention and expressed in grams, g/m, g/m2, and g/m2.7. The ECGs
      and Echos were recorded at baseline, 3 months, and annually for 4 years. The ECGs
      were computer processed to define the following criteria: (1) Casale/Devereux,
      (2) Cornell product, (3) Cornell voltage, (4) 12-lead voltage product, (5) sum of
      the 12-lead, (6) Rautaharju, (7) Sokolow-Lyon, and (8) Romhilt-Estes point score.
      The major findings were: (1) correlations between the ECG and Echo were modest
      for level and minimal for change, (2) Echo indexing did not alter correlations
      with ECG criteria, (3) white men and women show higher correlations for level and
      change than blacks, (4) repeatability of the Echo-LVM index was 0.7, making it a
      "moving" validity standard for the ECG, (5) further ECG modeling to predict Echo
      LVH, especially in whites, is not a productive approach, and (6) ECG measurements
      should be combined with other non-ECG characteristics when detecting LVH, and
      future ECG-LVM studies should investigate the prognostic value of ECG
      characteristics and use disease outcome as the validity standard.

PMID- 9238409
TI  - ECG identification of left ventricular hypertrophy. Relationship of test
      performance to body habitus.
AB  - Obesity is associated with the presence of left ventricular hypertrophy (LVH)
      and, conversely, with decreased sensitivity of the electrocardiogram (ECG) for
      LVH due to attenuating effects on QRS amplitudes. Although the Framingham
      adjusted Cornell voltage, incorporating age, sex, and body mass index (BMI), was
      developed to correct for the effects of obesity on the accuracy of the ECG, the
      impact of body habitus on ECG detection of LVH for newer, more accurate ECG
      criteria based on the time-voltage area under the QRS complex has not been
      determined. The authors examined the test accuracy of the Sokolow-Lyon voltage,
      Cornell voltage, Cornell product (product of QRS duration and Cornell voltage),
      Framingham-adjusted Cornell voltage, and time-voltage area of the horizontal
      plane vector QRS for the detection of echocardiographic LVH in relation to body
      habitus in 250 patients. Normal-weight or overweight status was based on sex
      specific population-based BMI partitions. Using partitions with a matched
      specificity of 98% in the overall population without LVH, the sensitivity of
      standard ECG criteria varied according to body habitus. Sensitivity of the
      Framingham-adjusted Cornell voltage was less in normal-weight than in overweight
      patients (49 vs 59%, P = .0004); there were also trends toward lower sensitivity
      in normal-weight patients for the Cornell voltage (40 vs 65%, P = .10) and the
      Cornell product (43 vs 65%, P = NS), but sensitivity of the Sokolow-Lyon voltage
      was lower in obese than in nonobese patients (18 vs 50%, P = .025). In contrast,
      the horizontal plane vector area had similar sensitivity in obese and normal
      weight patients (76 vs 74%, P = NS). Specificity varied with body habitus only
      for the Framingham-adjusted Cornell voltage: 100% in normal-weight vs 95% in
      overweight patients (P < .05). Thus, accuracy of the Framingham-adjusted Cornell
      voltage and Sokolow-Lyon voltage varies significantly with body habitus. In
      contrast, accuracy of the Cornell voltage and the Cornell product appears less
      dependent on BMI, and the time-voltage area of the QRS minimizes the effects of
      obesity on the accuracy of the ECG for LVH.

PMID- 9238410
TI  - Improved ECG models for left ventricular mass adjusted for body size, with
      specific algorithms for normal conduction, bundle branch blocks, and old
      myocardial infarction.
AB  - Considerable efforts have been invested recently to improve electrocardiographic
      (ECG) classification accuracy for left ventricular hypertrophy (LVH). This study
      examines how LVH classification accuracy is influenced by (1) the selection of an
      echocardiographic standard for LVH, (2) LVH severity level in the test groups,
      and (3) the adjustment of LVH criteria for obesity and age. Using data obtained
      from large, community-based populations, this study explores prospects for
      improving ECG models for LVH classification and examines some of the general
      characteristics of newer ECG models for estimating left ventricular mass (LVM) on
      a continuous scale. The results indicate that the apparent ECG classification
      accuracy for LVH is substantially influenced by echocardiographic standards and
      criteria for LVH, LVH severity level, and selection criteria for test
      populations, and these differences explain some of the often substantial
      differences in test results from clinical versus community-based evaluation
      studies. The low reproducibility of echocardiographic LVM as the standard is a
      limiting factor in attempts to improve ECG criteria for LVH and LVM prediction
      models. Adjustment of ECG amplitudes to anthropometric factors that
      simultaneously influence LVM may result in confounding effects and may lead to
      the development of inappropriate models. The performance of ECG models for LVM
      prediction improved substantially by the inclusion of body weight as a covariate
      with ECG variables. The addition of standing height and various covariates
      reflecting obesity did not improve LVM prediction accuracy. Compared to the older
      LVM prediction models of the Novacode ECG program, the correlation between
      echocardiographic and ECG estimates of LVM increased sufficiently (from 0.33 to
      0.54 in women and from 0.46 to 0.62 in men) to suggest that these improved ECG
      models are suitable for monitoring LVH progression/ regression in study groups
      participating in hypertension intervention trials.

PMID- 9238411
TI  - The standard 11-lead ECG. Neglect of lead aVR in the classical limb lead display.
AB  - This study investigates how the format of limb lead display influences
      electrocardiographic (ECG) interpretation. The positive aspect of lead aVR
      (included in the classical display) is directed opposite to that of the other
      leads. This could lead to an ECG interpreter's disregard of lead aVR, thus
      providing a "standard 11-lead ECG." It is hypothesized that when using the
      classical limb lead display, ECG interpreters often ignore lead aVR, even when
      considering complex ECGs. Thirty-five of the participants attending this
      International Society of Computerized Electrocardiology meeting were asked to
      interpret five complex ECGs, displayed in the classical format. Lead aVR had been
      replaced by lead -aVR on all of these recordings. Second, the participants were
      asked if they (1) used all 12 leads, (2) used lead aVR, and (3) noticed that lead
      aVR had been changed. The results indicate that a vast majority of interpreters
      (80-94%) did not detect when lead aVR had been reversed. This suggests that
      interpreters only use 11 of the standard leads when presented with the classical
      display method to evaluate clinical problems.

PMID- 9238413
TI  - Acquired immunodeficiency syndrome (AIDS)-data as at 30 June 1996.

PMID- 9238414
TI  - The current global situation of the HIV/AIDS pandemic.

PMID- 9238412
TI  - [Latinamerican consensus on diagnosis and treatment of asthma. Puebla, Mexico, 26
      28, February 1993].

PMID- 9238415
TI  - Zoonoses control. Equine morbillivirus in Queensland.

PMID- 9238416
TI  - Expanded programme on immunization (EPI). Adverse events following administration
      of measles-rubella vaccine.

PMID- 9238417
TI  - Lyme disease, 1995. United States of America.

PMID- 9238418
TI  - Joint United Nations Programme on HIV/AIDS (UNAIDS)-WHO. Revised recommendations
      for the selection and use of HIV antibody tests.

PMID- 9238419
TI  - [The latest on enteroviruses in human pathology].
AB  - Enteroviruses are small RNA viruses belonging to the Picornaviridae family. At
      least 65 serotypes have been described, including polioviruses, coxsackieviruses
      A and B, echoviruses and unclassified enteroviruses. Because of the absence of
      envelope they are relatively resistant to physical and chemical agents. They are
      mainly transmitted by the oral-fecal mode, but respiratory and mucosal
      transmissions are also possible. In humans, enteroviruses have been involved in
      miscellaneous acute infections and more recently in persistent infections
      (chronic meningoencephalitis in agammaglobulinemic patients, post-polio syndrome,
      chronic myocarditis and dilated cardiomyopathy, insulin-dependent diabetes
      mellitus...). Hypotheses in the relation between enterovirus persistence and
      chronic infections are formulated. The virological diagnosis of enterovirus
      infections is discussed, with a special focus on genomic application techniques
      (PCR) that are renewing the interest for this family of viruses in clinical
      pathology. If the role of enteroviruses in chronic pathologies is confirmed, the
      development of new therapeutic approaches (including vaccines and antiviral
      agents) will be needed.

PMID- 9238420
TI  - [Genetic hemochromatosis].
AB  - Haemochromatosis is the most common genetic disease in individuals of Northern
      European origin. This disorder of iron metabolism, for which the molecular basis
      remains poorly understood, is characterized by an excessive absorption of dietary
      iron through the duodenal mucosa. Progressive iron loading of parenchymal organs
      results in the mid-life onset of clinical complications, and patients may succumb
      to cardiac failure and/or hepato-carcinoma. But patients who undergo early
      diagnosis and phlebotomy treatment before the development of organ damage have a
      normal life expectancy. The haemochromatosis gene was recently isolated and
      encodes a HLA class I related protein. A missense mutation (C282Y) in the
      homozygous configuration was observed in more than 92% of the patients. So
      diagnosis and genetic counselling are getting modified by this direct genotyping
      test.

PMID- 9238421
TI  - [Glutathione peroxidases: value of their determination in clinical biology].
AB  - The role of glutathione peroxidase in the oxidative metabolism and recent
      advances in the demonstration of the consequences of the desequilibrium in the
      proxidant/antioxidant balance on biological molecules oxidation, intracellular
      signals transduction, apoptosis and necrosis, have led to new approach in the
      knowledge of many pathological processes. Methods for determining antioxidant
      capacity have been developed. The measurement of glutathione peroxidase activity
      is a key step in the study of oxidative stress. Its determination in clinical
      biology needs optimal conditions for standardised assays which will be used for
      epidemiological studies aimed to evaluate the role of nutritional factors
      involved in the pathogeny of diseases caused or accompanied by oxidative stress.

PMID- 9238422
TI  - [Detection of liver metastases from digestive cancer. Value of alkaline
      phosphatases, their macromolecular isoenzyme and of ceruloplasmin].
AB  - In order to improve the non aggressive diagnosis of hepatic metastasis from
      digestive neoplasm, the authors analyzed the following biological parameters:
      aminotransferases, alkaline phosphatase and lacticodehydrogenase isoenzymes,
      gammaglutamyl-transpeptidase, conjugated and total bilirubin, C-reactive protein,
      type A, G, M immunoglobulins, C3 complement factor, alpha-1 acidic glycoprotein
      (orosomucoid), haptoglobin, ceruloplasmin, transferrin, albumin, prealbumin,
      ferritin. This work included 54 patients with digestive tract cancer (esophageal,
      gastric, colic, rectal, anal localizations), divided in two groups: M- (n = 27),
      without hepatic metastasis), and M+ (n = 27, with histological confirmed hepatic
      metastasis). The Mann-Whitney test showed significant differences for 12
      parameters between the 2 groups. With more than 60% sensitivity (Se) and
      specificity (Sp), according to the ROC curves, the following parameters can be
      selected: Total alkaline phosphatase (Se 89%, Sp 70%) and their macromolecular H2
      fraction, lacticodehydrogenase fraction 4 (Se 63%, Sp 63%), gammaglutamyl
      transpeptidase (Se 85%, Sp 82%), ceruloplasmin (Se 64%, Sp 65%), aspartate
      aminotransferase determination (Se 63%, Sp 65%).

PMID- 9238423
TI  - [Evaluation of reticulocyte count on Cell-Dyn 3500 automate: comparison with a
      flow cytometry technique].
AB  - Cell-Dyn 3500 automate (Abbott) provides reticulocyte count using a recent
      software, after ribosomal RNA colouring with methylene blue reagent. The aim of
      this study was to evaluate results from Cell-Dyn 3500, and to compare them with
      the routine laboratory technique by flow cytometry (FacScan, Becton-Dickinson).
      Cell-Dyn 3500 analytical parameters (inter- and intra-assay precision, sample-to
      sample contamination) were good and in accord to manufacturer's specifications.
      Reticulocyte values from blood samples kept at 4 degrees C during 3 days were
      unchanged. Usual values in 145 normal patients were found between 71.3 and 78.3
      G/l with Cell-Dyn 3500, between 119.3 and 130.2 G/l with FacScan. Both techniques
      were compared in 87 patients with various anemias: Cell-Dyn 3500 showed more
      frequently high reticulocyte values in regenerative anemias (hemorrhagic), but
      was less performant for classification of aregenerative anemias. Reticulocyte
      count with Cell-Dyn 3500 is a semi automatic, easy to perform and swift
      technique, using no toxic reagent but unitary test tubes kept at room
      temperature. The test cost is however high, and Cell-Dyn 3500 cannot be used
      during the analysis.

PMID- 9238425
TI  - [A progress in the standardization in clinical enzymology using calibrators
      adapted to several techniques].
AB  - Results in enzymology obtained in routine conditions, differ considerably
      according to the measurement procedures, and the use of conversion factors is not
      an advisable solution. Some studies show that between-laboratory agreement of
      results can be improved by using validated enzyme calibrators. The conditions,
      which are required to define a strategy for the development of such calibrators,
      are described in a first part. The example of lipase activity, which is measured
      in routine conditions with important between-method discrepancy, is studied in a
      second part. This example emphasised the need of an a priori control of the
      validity of the calibrators. Under these conditions, between-method agreement is
      in fact considerably improved. With the collaboration of manufacturers for the
      development of validated enzyme multicalibrators, it will be possible to improve
      the efficiency of the information transmitted by clinical chemists to clinicians.
      Thus, enzyme activities measurements could benefit from the same improvement as
      immunoassay of proteins with the use of CRM 470 by manufacturers to calibrate
      their standards.

PMID- 9238424
TI  - [Value of the Remedi chromatography automate for the analytic diagnosis of drug
      poisoning].
AB  - The aim of this study was to evaluate the liquid chromatographic system Remedi
      (Biorad) in comparison with traditional immunological and colorimetric methods,
      for the diagnosis of acute drug overdose. 469 blood samples and 95 stomach
      cleaning liquid samples have been analysed during 1995. The usual toxicologic
      analysis was composed of the benzodiazepines, tricyclic antidepressants and
      barbiturates research. Ethanol, meprobamate and acetaminophen assays were
      performed only on physician's request. Only three pharmacological classes can be
      analysed both with immunological methods and Remedi: benzodiazepines, tricyclic
      antidepressants and barbiturates. Remedi has been found to be less sensitive than
      immunological method for benzodiazepines, it sometimes gave false negative
      results for barbiturates, but it was very efficient for antidepressants. Remedi
      often identified drugs other than the 3 previous classes: sedatives,
      antipsychotic, beta-blockers, antiarythmics. Furthermore these drugs are of
      clinical importance due to the fact that they are able to modify the
      symptomatology. In every case Remedi was able to give an estimation of the blood
      concentration of the toxic molecule matched. Remedi can not replace traditional
      methods but is a good complementary tool, available in emergency. This is
      particularly useful when clinical signs do not correspond to the toxics suspected
      by questioning the patient or relatives.

PMID- 9238426
TI  - [Lymphoproliferative syndrome in a 87-year-old patient: leukemic phase of mantle
      cell lymphoma or chronic lymphoid leukemia].

PMID- 9238427
TI  - [Residual presence of fibrinogen: frequent pitfall in the interpretation of serum
      protein electrophoresis].

PMID- 9238428
TI  - [Penicillium marneffei infection: a pathology to be known].

PMID- 9238429
TI  - [Apropos of a case of respiratory syncytial virus broncho-alveolitis].

PMID- 9238430
TI  - [Quality assurance, certification, accreditation, development toward a European
      harmonization].

PMID- 9238431
TI  - [GBEA and pipettes].

PMID- 9238432
TI  - [Role of enteroviruses in type I diabetes mellitus].

PMID- 9238433
TI  - [Single liquid phase calibration of instruments for blood gas and electrolyte
      analysis].

PMID- 9238434
TI  - [Neurologic involvement in Behcet's disease].

PMID- 9238435
TI  - [Neurologic manifestations in Behcet's disease. 16 cases in a cohort of 110
      patients].
AB  - OBJECTIVE: To discuss neurological involvement of Behcet's disease and
      therapeutical possibilities. PATIENTS: Among 110 patients with Behcet's disease,
      16 were found to have neurological involvement. All these patients fulfilled
      Japanese and International Study Group criteria for diagnosis of Behcet's
      disease. RESULTS: Central nervous system involvement was found in 15 patients and
      peripheral nervous system involvement in one. Meningoencephalitis and/or
      transverse myelitis were the most frequent features (69%) followed by tumor-like
      manifestations (13%); cerebral venous thrombosis was identified in 1 patient with
      occlusion of the left lateral sinus. Focal deficits were the major presenting
      signs and cranial paralysis were present in 19% of patients. In
      meningoencephalitis, the cerebrospinal fluid findings were lymphocytic
      pleocytosis and elevated protein level. Cerebral CT Scan, performed in 6
      patients, was normal in 33% of cases. MRI, performed in 4, showed abnormal
      signals distributed over hemispheric white matter, the brainstem and the thalamus
      in one patient, an occlusion of the left lateral sinus in the second one and a
      tumor-like lesion in the third. MRI abnormalities were associated with concording
      clinical deficits. CONCLUSION: Neurological involvement in Behcet's disease con
      be classified into 3 clinical aspects: meningoencephalitis (and/or myelitis),
      cerebral venous thrombosis and tumor-like features. Corticosteroids, when
      prescribed early, are useful and are associated with better prognosis.

PMID- 9238436
TI  - Differences in the effects of cytokines on the expression of adhesion molecules
      in endothelial cells.
AB  - OBJECTIVES: Expressions of adhesion molecules on arterial endothelial cells are
      crucial events in initiation of atherosclerosis. Our recent study has shown that
      endothelial cells express endothelial leukocyte adhesion molecule-1 (ELAM-1)
      significantly due to stimulation with oxidized LDL, H2O2, or hypoxia. This
      current study is aimed at investigating temporal relations of the induction of
      ELAM-1, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion
      molecule-1 (VCAM-1) in cultured endothelial cells of the human thoracic aorta.
      METHODS: The activators examined were interleukin 1 alpha (IL-1 alpha), tumor
      necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma). Cells were
      incubated with each of the cytokines at 10 ng/ml for 0.5-48 hours. The adhesion
      molecules were determined by enzyme immunoassay. RESULTS: ELAM-1 appeared after
      stimulations by IL-1 and TNF alpha; ELAM-1 was induced by IL-1 after one hour,
      while it rose sharply after a 30-min stimulation by TNF alpha. The ICAM-1
      expression was observed even in non-stimulated cells and further increased in
      proportion to duration of stimulation. No significant difference occurred between
      the effects of IL-1 and TNF alpha on the ICAM-1 expression. Weak expression of
      VCAM-1 was observed only by TNF alpha after 4-through 24-h stimulation. IFN gamma
      did not cause any changes in the expression of ELAM-1, VCAM-1, and ICAM-1.
      CONCLUSIONS: The present data indicate a specific time course for each induction
      of ELAM-1 and VCAM-1, but not ICAM-1. Therefore, the combination of molecules may
      play a role for endothelial cells to discriminate monocytes from such other cells
      as neutrophils and lymphocytes.

PMID- 9238437
TI  - [Veno-occlusive disease after bone marrow transplantation: preventive effect of
      heparin].
AB  - Liver veno-occlusive disease is a severe toxic effect observed after bone marrow
      transplantation. Clinical manifestations are jaundice, painful liver enlargement,
      and fluid-sodium retention. Histologically there is non-thrombotic obliteration
      of the centro-lobular veins associated with centro-lobular necrosis. This severe
      complication of bone marrow transplantation occurs early and is caused by a toxic
      processing effect. Incidence is variable, 2 to 50% in reported series, depending
      on patients, type of marrow provessing and on diagnostic criteria (which hinders
      comparison between studies). According to most studies, veno-occlusive disease
      regresses spontaneously. Mortality, depending on the severity of the symptoms,
      varies from 20 to 50%. Pathogenesis remains under debate: the initial event would
      occur in the sinusoid endothelium creating a state of local hypercoagulability by
      release of tissue factors favoring deposit of coagulation factors, especially
      factor VIII, in the subendothelial region of the veinules. There is also a direct
      toxic effect on centro-lobular hepatocytes which is further aggravated by
      ischemia and venous stasis. use of heparin to prevent veno-occlusive disease was
      proposed by the Besancon group in 1985 after they observed a low incidence (1
      case in 65) in patients who were given low doses of heparin to maintain patent
      central catheters. The same team confirmed in 1992 the low incidence in a large
      retrospective series of 444 patients given either an autograft (3 cases in 253
      patients, i.e. 1.2%), or an allograft (5 cases in 191 patients, i.e. 2.6%). Two
      single-center studies, one in Seattle and the other at the Saint-Antoine hospital
      in Paris, published in 1990 and 1991, did not show any difference in patients
      given heparin or not. Inversely, a randomized study published by Attal in 1992
      including 161 patients showed a significant difference in the incidence of veno
      occlusive disease between patients given heparin (2.5%) and those who were not
      given heparin (13.7%; p < 0.01). All these studies show that with low doses (100
      150 U/kg) the risk is very very low. The mechanism of action of heparin would
      appear to be related to its protective effect on the endothelium rather than its
      hemostasis effect. The vascular protective effect of prostaglandin E1 suggests it
      might also be useful in preventing veno-occlusive disease.

PMID- 9238438
TI  - [Thrombopenia induced by heparin. From physiopathology to treatment].
AB  - Heparin-induced thrombocytopenia is an uncommon but potentially dangerous adverse
      effect of heparin therapy. Late onset thrombocytopenia is usually observed
      several days after initiating treatment and can be distinguished from early-onset
      benign thrombocytopenia which is more moderate and transitory and which results
      from a direct interaction between heparin and platelet membrane proteins which
      potentialize ADP-induced aggregation. Severe late-onset thrombocytopenia clearly
      results from an immunological mechanism due to the development of heparin
      independent antiplatelet antibodies, often IgGs. These antibodies do not cause
      cell lysis but have a platelet-activating effect with release of the contents of
      the dense alpha granulations. This cell activation requires the formation of a
      heparin-dependent antibody-platelet complex. In most cases, platelet factor 4, an
      alpha granule protein, would be implicated. The antibody-platelet interaction has
      an activating effect following binding of the IgG Fc fragment to the Fc gamma RII
      receptor. The antibodies could also bind, favoring the development of thrombosis.
      The diagnosis of heparin-induced thrombocytopenia is evidenced by a platelet
      count under 100 Giga/l, usually from the 5th to 20th week of heparin therapy.
      Occasionally, the only sign is the low platelet count (drop of over 40% from
      pretreatment levels). Coagulation activation can lead to diffuse consumption
      coagulopathy in about 25% of the cases. Clinically, thrombosis is observed in
      about one half of the cases. Arterial thrombosis is the most characteristic and
      concerns the aorta and its branches as well as cerebral, coronary, mesenteric,
      renal and upper limb arteries. Venous thrombosis may be underestimated as they
      often occur as paradoxical recurrence after heparin therapy. Hemorrhage is much
      less frequent (less than 20% of cases) and often benign. To diagnose heparin
      induced thrombocytopenia, one must eliminate other potential causes (infection,
      drug...), observe complete normalization of platelet count after heparin
      withdrawal, and demonstrate heparin-dependent antibodies in the plasma or serum.
      Different laboratory tests are quite helpful but have variable sensitivity. The
      incriminated heparin must be discontinued immediately. Use of low-molecular
      weight heparins, even when cross-reactivity is not demonstrated in vitro, is not
      recommended. Other compound however, such as Orgaran 10,172 (or Lomoparan, appear
      to be the best choice. The action of antivitamin K agents is delayed and, due to
      the early dissociated drop in protein C at the beginning of treatment further
      raise the major risk of thrombosis. Classic antiplatelet agents such as aspirin
      are ineffective if used alone. More powerful compounds such as Ilomedine, are not
      available for this indication and are difficult to titrate. Part of the
      therapeutic problem with heparin-induced thrombocytopenia may be resolved with
      the advent of molecules with a direct antithrombin effect such as hirudine or its
      analogues. As suggested by a recent study, widespread use of low-molecular-weight
      heparin will undoubtedly have a highly significant effect on reducing the number
      of cases of severe thrombocytopenia.

PMID- 9238439
TI  - [Platelet factor 4, target of anti-heparin antibodies: application to biological
      diagnosis of heparin-induced thrombopenia].
AB  - Heparin-platelet factor 4 (H-PF4) complexes are the target for heparin-dependent
      antibodies present in most of heparin-induced thrombocytopenias (HIT). The
      highest reactivity is obtained with 27 IU of heparin per mg of PF4. Low molecular
      weight heparin (LMWH) and pentosane polysulphate can also form these complexes.
      Antibodies to H-PF4, may be of the IgG, IgA or IgM isotypes. In some HIT, IgGs
      are absent and only IgMs and/or IgAs are observed. These antibodies may also
      develop in heparin (15%) or LMWH (8%) treated patients in the absence of
      thrombocytopenia. IgGs rarely develop in these cases. Presence of antibodies to H
      PF4 is therefore a risk factor for developing HIT. Development of pathology
      requires additional factors such as: PF4 and heparin at an optimised ratio
      allowing formation of macromolecular complexes; presence of activated platelets
      exposing increased Fc gamma RII-A and heparin receptors; His. 131 phenotype of Fc
      gamma RII-A; pre-thrombotic and/or inflammatory clinical manifestations. Assay of
      antibodies to H-PF4 improves HIT diagnosis and could be predictive for monitoring
      heparin-therapies.

PMID- 9238440
TI  - [Effects of heparin on megakaryocytopoiesis. From fundamental data to clinical
      applications].
AB  - Heparin, a glycosaminoglycan (GAG) derivative has been widely used as an
      anticoagulation agent for more than 50 years. This study was conducted to
      demonstrate that, due to their modulatory effect on cytokines, heparin and other
      GAGs can favor megakaryocytopoiesis both in vitro and in vivo in mice. In vitro
      addition of heparin and other GAGs (excepting keratane sulfate) into plasma clot
      cultures induces a significant increase in the number of megakaryocyte colonies.
      Optimal heparin and GAG concentrations for maximal effect are approximately 50
      100 micrograms/ml. In agar culture without serum, all GAGs do not have this
      stimulating effect on megakaryocyte colonies. This would suggest that the GAG
      action depends on the presence of one or more plasma factors. Interactions
      between GAGs and cytokines such as IL3, IL6, G-SCF, GM-CSF, aFGF, TPO and EPO as
      well as PF4 and TGFB1 were also conducted. The results demonstrate that heparin
      and chondroitin sulfate significantly increases the action of TPO, IL6 and aFGF
      but not the action of IL3, G-SCF and EPO. Heparin and other GAGs can also
      neutralize PF4 and TGFB1 inhibitory action. In vivo, the effect of low-molecular
      weight heparin (Fraxiparine) injected in normal mice treated with 5-fluorouracil
      increases megakaryocytopoiesis. The findings demonstrate that heparin and its
      derivatives have a potentializing effect on megakaryocytopoiesis and could be
      used as therapeutic agents in the treatment of thrombocytopenia.

PMID- 9238441
TI  - [Current indications of low-molecular-weight heparins].
AB  - Low-molecular-weight heparins (LMWH) have different properties than non
      fractionated heparins. Bioavailability is better after subcutaneous
      administration and a longer halflife allows a single daily injection. Efficacy is
      equivalent for postoperative thromboembolism prophylaxis for all types of
      surgery. In most reports, low-molecular-weight heparins are more effective than
      non fractionated heparin and lead to fewer episodes of hemorrhage and
      thrombocytopenia. For treatment of deep vein thrombosis, low-molecular-weight
      heparins are as effective as non-fractionated heparins after two, or even one,
      daily injection without hemostasis tests. Other on-going studies are evaluating
      LMWH indications in pulmonary embolism, artery disease, pregnancy or other
      medical conditions.

PMID- 9238442
TI  - [Characteristics of rapid progressors in HIV infection].
AB  - Approximately 10% of HIV-infected patients, the rapid progressors, progress to
      AIDS within the first 2 to 3 years of HIV infection. Their biological
      characteristics are not clearly known. They have a particular phenotype (DR) of
      major histocompatibility complex class-II. Anti-HIV antibodies are not
      neutralizing and may even be facilitators in vitro. Progressors CTL responses are
      also defective and the production of the cytokines, specially the chemokines
      RANTES, MIP-1 alpha et MIP-1 beta which may have a role in inhibition of cellular
      infection by HIV, is impaired. In addition, the rapid progressors have high
      levels of inflammatory markers which suppose a chronic activation of the immune
      system. The virological findings are more inconsistent. A uniform finding is a
      high viral load that does not fall dramatically after primary HIV infection. Some
      rapid progressors may be infected with more rapidly replicating, virulent HIV
      strains. However, the question regarding the homogeneity or the other
      characteristics of viral load remains to be resolved.

PMID- 9238443
TI  - [Current status in the prevention of Mycobacterium avium complex infections in
      patients with HIV infection].
AB  - Mycobacterium avium complex (MAC) infections in AIDS are increasingly common and
      contribute to the mortality in severe immunocompromised patients. In this paper,
      we review the published studies on the prevention of the MAC infections.
      Rifabutin and the new macrolides (clarithromycin, azithromycin) are shown to be
      effective in the primary prevention. However, they can fail and are difficult to
      manage with the antiretroviral treatment, specially antiproteases and prevention
      of the other opportunistic infections. For the prevention of the relapse of the
      MAC infections, it is necessary to give a prolonged treatment with a bio-therapy
      associating at least a new macrolide with rifabutin or ethambutol, which is also
      difficult to manage with the other treatments.

PMID- 9238444
TI  - [Value of desensitization for reintroducing trimethoprim-sulfamethoxazole in
      hypersensitive patients with HIV infection].
AB  - The incremental administration of trimethoprim-sulfamethoxazole (i.e.,
      desensitization) in previously hypersensitive HIV-infected patients has been
      evaluated to date in 7 studies involving more than 10 patients. These studies
      differ greatly from one to another according to the inclusion criteria, exclusion
      criteria, and desensitization procedure (duration, lagtime between 2 doses). The
      efficacy varies from 33% to 100% but one can expect success in 3 out of 4
      patients whatever the duration of the desensitization procedure. Short procedures
      seem better than long ones from the compliance point of view. These different
      procedures have not been compared each other. The reputation of good tolerance of
      this procedure is challenged by the recent description of severe life-threatening
      systemic reaction. Subsequent contra-indications must be ruled out and this
      procedure must be supervised in hospital.

PMID- 9238445
TI  - [Extrapulmonary and disseminated pneumocystosis in AIDS. A review of the
      literature].
AB  - We present a literature review about extrapulmonary and disseminated
      pneumocystosis in AIDS. The prevalence of such infections seems low but is
      probably under-estimated. Disseminated pneumocystosis occurs in patients with
      profound immunosuppression, who do not receive prophylaxis against Pneumocystis
      carinii pneumonia or are treated with aerolized pentamidine. The lack of
      specificity of symptoms may delay the diagnosis. Most organs may be involved.
      Three different presentations may be individualized: disseminated pneumocystosis,
      intra-thoracic only disseminated pneumocystosis, in an intra-thoracic
      localization alone, and localized extrapulmonary pneumocystosis. The mortality
      from disseminated disease is high, especially in the presence of low serum
      albumin level.

PMID- 9238446
TI  - [Splenic pneumocystosis disclosing extrapulmonary pneumocystosis of fatal
      outcome].

PMID- 9238447
TI  - [Hyperkalemia and acute renal insufficiency during overdose of trimethoprim
      sulfamethoxazole in a patient with AIDS].

PMID- 9238448
TI  - Aelius Aristides and the therapeutic dream in the second century.

PMID- 9238449
TI  - Hafnia alvei septicemia in two patients with digestive malignancies.

PMID- 9238450
TI  - [Abdominal pseudo-eventration disclosing Lyme disease].

PMID- 9238451
TI  - [Pubic septic osteoarthritis of athletes. A case complicated by deep venous
      thrombosis].

PMID- 9238452
TI  - [Radiofrequency ablation of accessory atrioventricular pathways].
AB  - Since its introduction at the beginning of the 1980s, radiofrequency ablation of
      accessory atrioventricular pathways has become method because of its excellent
      results and the indications have increased to cases in which only symptomatic
      improvement is the objective. These advances have been made possible by technical
      innovations to the generators of the radiofrequency current and, above all, to
      the ablation catheters which enable mapping nearly all the perimeter of the
      atrioventricular rings and reach all the accessory pathways irrespective of their
      site. The approach depends on the localisation of the accessory pathway but the
      criteria of mapping are the same: detection of a specific accessory pathway
      potential, precession or concordance (depending on the topography) of the initial
      peak of the endocavitary ventriculogramme and the onset of the delta wave on the
      surface ECG, QS morphology of the ventriculogramme on monopolar recording,
      shortest VA' interval in orthodromic reciprocating tachycardia for latent kent
      bundles. In specialised centres, the global success rate is 90 to 98% but certain
      sites, especially the right lateral pathways, are more difficult to attain. The
      complication rate is about 4% but it tends to decrease with the experience of the
      operating teams and close monitoring of the patients. However, there persists an
      uncertainty concerning potentially arrhythmogenic effects of the lesions induced
      which justifies restricting the indications in young children.

PMID- 9238453
TI  - [An update of surgery for ventricular tachycardia].
AB  - The implantable defibrillator has, to a certain degree, taken over some of the
      indications of antiarrhythmic surgery in ventricular tachycardia resistant to
      drug therapy. Initially reserved for patient with ventricular aneurysms, this
      form of surgery may also be proposed for patients with localised infarction. The
      multiplicity of forms of tachycardia, the variability of their mechanism which is
      not always limited to the subendocardial layers requires mapping procedure to
      guide the surgical intervention on the arrhytmogenic substrate. The so-called
      regional procedures which, for most workers, combine resection and cryo-ablation,
      is a good compromise between risk and efficacy. This surgery used to be
      associated with a high mortality but this has been considerably reduced by
      technical advances in myocardial protection. Similarly, the failure rate has also
      been reduced by the identification of "atypical" mechanisms. These improvements
      have been obtained thanks to systems of mapping which allow investigation of the
      epicardium/endocardium relationship and activation of the deep septal regions.
      Although the two techniques are not designed for the same type of patient, global
      mortality of surgically treated patients in the long term is not different to
      that of patients with an implantable defibrillator. Clinical efficacy of
      antiarrhythmic surgery is over 90% at 5 years in the majority of large scale
      trials. This type of surgery is the only really radical approach because of the
      limitations of catheter ablation and should be considered to be complementary to
      the implantable defibrillator in the management of post-infarction ventricular
      tachycardia.

PMID- 9238454
TI  - [Etiologies of electric storm].
AB  - The electrical storm is defined as recurrent ventricular tachycardia or
      fibrillation leading to cardiac shock occurring two or more times within 24 hours
      and usually requiring cardioversion or defibrillation. Recent advances in our
      understanding of this severe arrhythmia and its pharmacological treatment have
      improved the prognosis of these patients. The authors review several clinical
      syndromes of the electrical storm and the treatment of each.

PMID- 9238455
TI  - [Classification of regular atrial tachycardia].
AB  - ECG criteria which for many years formed the basis of the classification of
      regular atrial tachycardias may now be completed by the results of endocavitary
      studies (stimulation and mapping). Flutter is a macroreentry phenomenon in the
      right atrium, anticlockwise in typical, common or classical forms, and more
      variable in atypical forms: sometimes antidromic and clockwise, sometimes
      functional more rapid without a gap of excitability, or in other cases, skirting
      around the sears of atriotomy, especially right-sided. Tachycardias are
      paroxysmal and often secondary to reentry; more rarely permanent, they are then
      often due to increased automaticity especially in young patients. The concordance
      with surface ECG changes is not perfect and the distinction between flutter and
      tachycardia often depends on the frequency of the tachycardia and the leads
      studied.

PMID- 9238456
TI  - [Pharmacological treatment of atrial fibrillation].
AB  - Atrial fibrillation is not a single entity. Many factors play a role in its
      genesis, its maintenance and termination. The presence of underlying cardiac
      disease and left ventricular dysfunction is a major factor due to the
      electrophysiological and haemodynamic consequences, the effect on autonomic
      nervous system and on the effect of antiarrhythmic drugs themselves. It is
      therefore essential to take this into account before deciding on a therapeutic
      approach. This also emphasises the difficulty of interpreting clinical trials
      comparing pharmacological treatments when the study population is poorly defined.
      In general, one molecule is not more or less effective than another, it is more
      or less adapted to the patient under treatment.

PMID- 9238457
TI  - [Classification and pitfalls of atrioventricular blocks].
AB  - Atrioventricular blocks may be classified according to their degree, their site
      and their aetiology. Assessing the degree of block is not always easy when the P
      waves are poorly visible and/or masked by the ventricular complexes. Affirmation
      that a 2nd degree block is a Mobitz II block requires examination of the ECG to
      differentiate it from "false" Mobitz II due to variable PP intervals or concealed
      hisian extrasystoles. Complete atrioventricular block is easy to define on the
      ECG but not always synonymous with totally blocked conduction and should be
      interpreted taking into account the frequency of escape beats. Determining the
      site of block is important as it has therapeutic implications; the type of block
      evaluated from the surface ECG also provides useful but not always decisive
      information. The investigation of the aetiology of the block is valuable for
      differentiating acute, transient blocks from chronic (permanent or paroxysmal)
      blocks, the former sometimes requiring temporary but rarely permanent cardiac
      pacing.

PMID- 9238458
TI  - [Hereditary cardiac arrhythmia].
AB  - Progress in molecular biology has advanced our medical knowledge. The
      identification of genetic abnormalities has been transformed into the new
      approach of "inverse genetic s" which is based on close collaboration between
      clinicians, geneticians, molecular biologists and physiologists. In monogenic
      affections of unknown mechanism, the scientific method of determining the culprit
      gene is based essentially on precise phenotypic identification of all members of
      a large family and on DNA studies. The following steps consist in localising the
      gene with polymorphic genetic probes and then demonstrate the causal mutations
      and, finally, reexpress the normal and abnormal genes to study their function and
      thereby confirm the mutation. This approach has recently been applied to cardiac
      arrhythmias. Genes responsible for atrioventricular conduction defects, Wolff
      Parkinson-White syndromes associated with hypertrophic cardiomyopathy and
      arrhythmogenic right ventricular dysplasia have been localised in the human
      genome showing that these syndromes are often very variable. The greatest
      progress has been achieved in the congenital long QT syndrome. Four genes have
      been localised on chromosomes 3, 1, 7 and 11, and three have already been
      identified which has allowed study of their function and genotype-phenotype
      analysis.

PMID- 9238459
TI  - [Large coronary artery aneurysms. A study of 20 clinical cases in the elderly].
AB  - The aim of this study was describe the anatomical features of coronary aneurysms
      and assess their role in causing death. Twenty clinico-pathological cases were
      recensed prospectively out of 8,920 autopsies (0.22%). The average age at death
      was 68 +/- 20 years (14 men and 6 women). Death was due to a cardiac cause in 90%
      of cases. The aneurysms were located on a single coronary artery in 14 cases, on
      2 coronary arteries in 3 cases, and on all three arteries in 3 cases with a mean
      maximum diameter of 15 +/- 4.5 mm. Aneurysms of the right coronary artery were
      the most common (p < 0.01) and the largest (16.7 +/- 3.8 mm; p = 0.12) and
      circumflex arteries (12 +/- 3.1 mm, p = 0.03). The diameter of the coronary
      aneurysm was greater in the more elderly patients (r = 0.51 ; p = 0.022). The
      coronary aneurysms were diffuse in 10 subjects and localised in the other 10
      (mainly fusiform and proximal). Only 3 aneurysms were directly associated with
      significant stenosis of the same artery. The aetiology was atherosclerosis in 18
      cases, with associated extra-cardiac disease in 14 cases; the other 2 cases were
      dystrophic. The underlying anatomical abnormality constantly found was variable
      degrees of atrophy and destruction of the musculo-elastic elements of the media,
      a source of dilation. In 80% of cases, thrombosis of the aneurysm was directly or
      indirectly responsible for death. Coronary artery aneurysms are a rare finding
      and are frequently complicated by fatal thrombosis. Coronary angiographic
      detection of this condition characterised by the large size and absence of
      stenosis of the artery should lead to prophylactic antithrombotic therapy.

PMID- 9238460
TI  - [Coronary bypass in patients with severe left ventricular dysfunction (EF < or =
      25%). Apropos of 111 patients].
AB  - One hundred and eleven patients with severe left ventricular dysfunction (EF < or
      = 25%) underwent coronary bypass surgery between January 1984 and December 1994.
      The selection criteria were based on the measurement of an EF < or = 25%, LVEDP
      and CI. All patients had angina and 83 had signs of pulmonary oedema or episodes
      of congestive failure. Patients with valvular disease, left ventricular
      aneurysms, reoperations, surgery for arrhythmias and prior angioplasty, were
      excluded. The coronary disease usually involved all three vessels. Seventeen
      patients had lesions of the left main stem associated with lesions of the right
      coronary artery. The average number of bypass grafts was 2.6 +/- 1.6 per patient.
      The average duration of aortic clamping was 60 +/- 19 minutes. Operative
      mortality (first month after surgery) was 10 patients (9%). The operative risk
      factors were: gender, stage of cardiac failure, emergency surgery, LVEDP > 23
      mmHg (p < 0.05), CI < 21/min/m2 (p < 0.05). The mean follow-up period was 42 +/-
      months (3 lost to follow-up). Late mortality was 42 patients. The one year
      actuarial survival was 88 +/- 5.3%, 76 +/- 9% at 3 years, and 56 +/- 18% at 6
      years. Long-term functional results were related to: preoperative stage of
      cardiac failure (NYHA stage IV) and the association of raised LVEDP and low CI.
      Surgical results remained satisfactory, however, and the surgical indication was
      justified in selected patients despite severe left ventricular dysfunction in
      cases usually with stable invalidating or unstable angina, in the knowledge that
      myocardial deterioration is progressive in the medium-term with a high incidence
      of cardiac failure.

PMID- 9238461
TI  - [Outcome of traumatic tricuspid insufficiency, treated surgically. Apropos of 9
      cases].
AB  - Between 1983 and 1992, 9 patients with traumatic tricuspid regurgitation
      underwent surgical correction. The population consisted of young male adults
      (mean age 39 years). The trauma was usually due to a road traffic accident (n =
      6). The mean interval to diagnosis was long (11 years). Echocardiography was
      diagnostic and showed the mechanisms. The usual lesion observed at surgery was
      subvalvular rupture of the anterior papillary muscle (n = 5). Surgery consisted
      of valve repair with annuloplasty and eight valve replacements for chronic
      retractile lesions. Six patients are still being followed up (average 7 years).
      There were no peroperative complications. Two patients underwent a second valve
      replacement for degeneration of a bioprothesis. Conduction defects requiring
      permanent cardiac pacing were not uncommon (n = 3) The delay before diagnosis may
      be explained by the diversity of lesion of the tricuspid valve, associated
      cardiac disease and the requesting of echocardiography. Surgical indications are
      mainly based on clinical signs. Even if long-term results are satisfactory,
      earlier diagnosis would probably allow more conservative surgery with
      preservation of right ventricular geometry and function.

PMID- 9238462
TI  - [Intermediary results with the CarboMedics bileaflet valvular prosthesis].
AB  - From December 1988 to December 1995, 212 patients underwent valve replacement
      with a CarboMedics bileaflet valve in our institution (103 aortic valve
      replacements, 72 mitral valve replacements, and 37 double valve replacements).
      Fifty-five percent were male patients. Mean age was 53.8 +/- 12.7 years. Forty
      seven percent of patients were in NYHA clinical status III or IV. Operative
      mortality was 3.7% (8/212). All patients but eight were followed-up for an
      average of 2.9 years after their operation and total follow-up was 617 patient
      years. At the time of the study, more than 90% of patients were in NYHA class I
      or II, 26% were in atrial fibrillation and 100% of patients received
      anticoagulation treatment. There were 15 late deaths. After 7 years, the
      actuarial survival rate was 84 +/- 7%. Three patients died of valve-related
      causes. Valve-related complications included 5 thromboembolic episodes (0.8%
      patient-year), 18 anticoagulant-related complications (2.9% patient-years), 3
      endocarditis (0.5% patient-year), and 4 reoperations (0.6% patient-year). After 7
      years, freedom from thrombo-embolic complication was 97 +/- 2%, from
      anticoagulant-related complications was 88 +/- 6%, from endocarditis was 96 +/-
      4%, and from reoperation was 95 +/- 5%. We conclude that the 7-year results
      compare with other bileaflet valves. More follow-up and larger studies are
      mandated to give definite conclusions.

PMID- 9238463
TI  - [Transthoracic echocardiography and diagnosis of acute pulmonary embolism. Change
      in the diagnostic valve with respect to thresholds of classification].
AB  - The diagnostic value of transthoracic echocardiography in acute pulmonary
      embolism is not well established. Although many parameters are abnormal, the
      thresholds used vary according to the authors, limiting the contribution of the
      investigation to the diagnosis. In a prospective study of 70 patients with
      suspected acute pulmonary embolism without previous cardio-respiratory disease,
      the authors tried to determine the diagnostic thresholds using discriminating
      linear analysis and ROC curves. Parameters easily recorded in an emergency were
      analysed: end diastolic ventricular dimensions, ratio of these diameters and
      maximal velocity of tricuspid regurgitant flow. Thirty-one patients had pulmonary
      embolism quantified by the Miller index (average: 16 +/- 7, range 2 to 28).
      Measurements of left ventricular dimension were disappointing (sensitivity: 0.52,
      specificity: 0.73 for a threshold value of 45 mm). The right ventricular
      dimension was a better predictive parameter (sensitivity: 0.70, specificity: 0.86
      for a threshold value of 25 mm). However, the ratio of right to left ventricular
      dimension had a better diagnostic value (sensitivity: 0.85, specificity: 0.78 for
      a threshold value of 0.5). The best diagnostic parameter was the maximal velocity
      of tricuspid regurgitation (sensitivity: 0.93, specificity: 0.82 for a threshold
      value of 2.5 m/s). The authors conclude that the maximal velocity of tricuspid
      regurgitation with a threshold of 2.5 m/s and the ratio of the ventricular
      dimensions with a threshold value of 0.5 are valuable diagnostic indicators for
      acute pulmonary embolism.

PMID- 9238464
TI  - [Mediastinitis after sternotomy. Mortality and hospital length of stay. Groupe
      parisien detude des sternotomies].
AB  - The morbidity of deep sternal wound infections after sternotomy was assessed by a
      case-controlled study. The 41 cases were identified by a prospective enquiry over
      4 months in 10 centres of cardiac surgery in the Paris region. The cases were
      compared with 41 non-infected controls, paired by centre, age, gender, ASA
      anaesthetic risk, stage of cardiac failure and type of surgery. The criteria of
      pairing were respected in 96% of cases. The mortality was 12% in the study
      population and 5% in the controls. Thirty-two of the 41 cases required
      reoperation for the sternal wound infection, usually to insert Redon drains after
      debridement of the wound. The total duration of the hospital stay was 53 days in
      the study cases and 30 days in controls, a median prolongation of the hospital
      stay of 23 days. The authors conclude that deep wound infection after sternotomy
      is responsible for almost doubling the duration of hospital stay. The economic
      consequences alone justify active research into the prevention of this
      complication.

PMID- 9238465
TI  - [Reproducibility of measurements of blood gas exchange during exercise in mild
      cardiac failure: need for a preliminary test?].
AB  - The reproducibility of blood gas exchange measurements on exercise in chronic
      cardiac failure has already been established in patients familiar with this
      technique. The aim of this prospective study was to evaluate the reproducibility
      of cardiopulmonary parameters on exercise in a population of patients who had
      never undergone this type of investigation. Twenty patients with chronic cardiac
      failure in classes I to III of the NYHA classification, with a mean age of 55 +/-
      11.5 years and a mean LV ejection fraction of 31.2 +/- 9%, underwent two
      cardiopulmonary exercise tests (CPX Medgraphic) performed on a bicycle ergometer.
      Patients underwent maximal exercise stress testing attaining 89% of the
      theoretical maximal heart rate and 1.14 of the respiratory quotient during the
      first test. There was no significant change in peak VO2 (22.5 ml/min/kg vs 22.6
      ml/min/kg) or in ventilatory anaerobic threshold (12.8 ml/min/kg vs 12.7
      ml/min/kg) between the two tests. The ventilatory anaerobic threshold could not
      be measured in one patient and seemed less reproducible than peak VO2 with a
      standard deviation of relative differences (T2-T1/T1) of 10.4 versus 7.8%. There
      was a significant increase in the duration of exercise (7.4 +/- 9.2%; p < 0.002)
      and a ventilatory flow (4.5 +/-, p = 0.03). This study shows that peak VO2 is a
      reproducible measurement in mild to moderate chronic cardiac failure, even in the
      absence of a preliminary test to familiarize the patient with the equipment. The
      reproducibility of the ventricular anaerobic threshold is less satisfactory than
      that of peak VO2. The increase in the duration of exercise is more dependent on
      motivation and should not be taken into account alone in the functional
      evaluation of chronic cardiac failure.

PMID- 9238466
TI  - [Epidemiology of sudden coronary death in France (1985-1982)].
AB  - The physiopathology of sudden coronary death (SCD) is well known. However, its
      impact on the population of France has not been studied in depth. The MONICA
      project recenses all coronary events in subjects of 25 to 64 years of age in a
      given geographic area. The definition of SCD is coronary death occurring less
      than one hour after the onset of symptoms. Out of 4,004 coronary deaths recorded
      from 1985 to 1992 in the Bas-Rhin and Haute-Garonne departments, 48% in men and
      43% in women were SCD. This event occurred outside hospital in 89% of men and 85%
      of women. SCD was the first ischaemic symptom in 61% of SCD in men and in 74% of
      women. Of the SCD occurring outside hospital, 2 to 6% of men and 6 to 7% of
      women. received emergency treatment in less than 5 minutes. The frequency of SCD
      increased with age and was highest in men. Between 1985 and 1992, standardised
      rates (35-64 years) in men fell from 62 to 48/100,000 in the Bas-Rhin (p < 0.01)
      and from 59 to 36/100,000 in the Haute-Garonne (p < 0.0001); in women, the
      frequency fell from 17 to 8/100,000 in the Bas-Rhin (p < 0.01) and remained
      stable in the Haute-Garonne (10/100,000 to 11/100,000). In conclusion, for the
      first time in France, accurate epidemiological data on SCD is presented,
      underlying its importance in terms of public health.

PMID- 9238467
TI  - [Repolarisation anomalies simulating anterior myocardial infarction during
      ischemic cerebrovascular accident].
AB  - The authors report the case of a woman admitted to hospital for minor trauma of
      the left hip and who presented major ST segment elevation on the second day
      suggesting an acute anterior wall myocardial infarction at the same time as a
      cerebrovascular accident. Complementary investigations and follow-up excluded the
      diagnosis of myocardial infarction with normalisation of the ECG on the 5th day.
      ECG changes during cerebrovascular accidents may be very variable ranging from
      extrasystoles to ST elevation mimicking myocardial infarction. They carry a poor
      prognosis with an increased risk of sudden death necessitating continuous ECG
      monitoring until the ECG reverts to normal. The cardiac involvement is not
      ischaemic but due to disease of the insular cortex of the brain which induces
      myocytolysis (centered around the intra-cardiac nerve endings) due to the sudden
      liberation of catecholamines. These lesions may be treated by propranolol or
      phentolamine.

PMID- 9238468
TI  - [Erdheim-Chester disease. Survey of a rare non-Langerhans histiocytosis].

PMID- 9238469
TI  - [Correlation between cup disk ratios and changes in visual fields in Togolese
      patients].
AB  - BACKGROUND: We have undertaken this study to analyze the correlations existing
      between Goldmann perimetry and cup disc ratios in Togolese patients less than 45
      years old. METHODS: Male and female outpatients presenting with cup disc ratio of
      0.4 or over underwent Goldmann perimetric examination. RESULTS: There were 120
      patients, 60 males and 60 females. Goldmann perimetry was normal in 3% cases. The
      62% remaining abnormal cases comprised central and paracentral defects,
      peripheral depression, nasal steps and tubular fields. These defects were
      variously correlated to the cup disc ratios. CONCLUSION: Goldmann perimetry is
      less used since the introduction of automated perimetry; however it is still
      helpful in our particular countries. Due to the various correlations between the
      cup disc ratios and Goldmann perimetric defects, we have to strengthen the follow
      up of patients whose first manual perimetry seems to be normal.

PMID- 9238470
TI  - [Tonometric course after trabeculectomy. Apropos of 105 cases at the Lome UHC].
AB  - BACKGROUND: This study has been conducted in order to assess tonometric changes
      after trabeculectomies without antimetabolites in primary open angle glaucoma.
      MATERIAL AND METHODS: One hundred and five eyes (105) in 64 patients with
      complicated open angle glaucoma with drug-resistant intraocular pressure or
      presenting disease progression were followed for 36 months. RESULTS: The mean
      intraocular pressure before surgery was 32.24 mmHg. Success rate (IOP < 21 MMhG
      without additional medical treatment) assessed with the Kaplan-Meier method was
      64% at 12 months, 60% at 24 months and 56% at 36 months. CONCLUSION: In our
      experience, many factors including the cost of medical treatment are discussed
      before the surgery. Our success rate probability was average. Antimetabolites and
      medical additional treatment are needed for improvement.

PMID- 9238471
TI  - [Retinectomies in the treatment of retinal detachments with vitreoretinal
      proliferation].
AB  - PURPOSE: To investigate the anatomical and functional results of retinectomy in
      the treatment of complex retinal detachment. METHODS: We reviewed the files of 48
      patients who underwent peripheral retinectomy of 90% or more for retinal
      detachment with anterior proliferative vitreoretinopathy stage A1 (6 cases), A2
      (23 cases, A3 (11 cases) or A4 (8 cases). Retinotomy was performed when complete
      reattachment of the retina posterior to the buckling was not obtained despite
      careful dissection of the peripheral vitreoretinal contraction. Retinotomy was
      completed by excision of the anterior retinal flap. After perfluorocarbon liquid
      injection, laser retinopexy and perfluorocarbon-silicone exchange were performed.
      RESULTS: Silicone oil was removed from 46 eyes (96%). The retina remained
      attached in 37 eyes (77%) with a visual acuity of 1/20 or more in 19 of them.
      Functional results did not correlate with the size of the retinectomy. The major
      complications were retraction of the retinectomy edge and recurrence of
      proliferative vitreoretinopathy, responsible for anatomic failure in 9 of the 11
      cases. Hypotony (i.e. intraocular pressure of 5 mmHg or less) only occurred in 6
      of the 37 successful cases. CONCLUSION: Retinectomy is a useful surgical tool for
      eyes with advanced proliferative vitreoretinopathy when careful membrane
      dissection and encircling buckling seem to be insufficient to obtain retinal
      setting. Its success rate is good and leads to relatively few complaints.

PMID- 9238472
TI  - [Evaluating the results of surgery of choroidal neovessels].
AB  - BACKGROUND: Subfoveal choroidal neovascularization has usually a poor visual
      prognosis. Submacular surgery has been advocated as an alternative treatment.
      Visual results of this recent surgical technique is under current clinical
      evaluation. METHODS: We retrospectively reviewed the charts of 16 eyes from 15
      patients who underwent submacular surgery through a small retinotomy. Mean follow
      up was 8 months (range from 5 to 88 weeks): group 1: submacular hemorrhages
      caused by age-related macular degeneration, 8 eyes; group 2: advanced subfoveal
      choroidal neovascularization in age-related macular degeneration, 3 eyes; group
      3: young onset subfoveal choroidal neovascularization, 5 eyes. RESULTS: Group 1:
      mean preoperative visual acuity was 0.024. Postoperative visual acuity increased
      for 5 eyes (63%) and decreased for 3 eyes (37%) (mean follow-up: 33 weeks). Two
      eyes had recurrent neovascularization. Group 2: mean preoperative visual acuity
      was 0.083. Postoperative visual acuity decreased for both eyes (mean follow-up:
      58 weeks). Two eyes had recurrent neovascularization. Group 3: mean preoperative
      visual acuity was 0.082. Postoperative visual acuity increased for both eyes
      (mean follow-up: 26 weeks). Two eyes had recurrent neovascularization. In both
      groups, recurrent neovascularization was managed by laser photocoagulation.
      CONCLUSIONS: Surgery of subfoveal choroidal neovascular membranes may stabilize
      or improve visual acuity in young patients. In subfoveal choroidal
      neovascularization due to age-related macular degeneration. this technique does
      not provide currently measurable visual improvement except in cases complicated
      by submacular hemorrhage. Results of future trials comparing surgery with
      spontaneous evolution or laser photocoagulation are necessary.

PMID- 9238474
TI  - [Congenital pit of the optic disk in indocyanine green].
AB  - PURPOSE: Etiopathogeny of serous retinal detachment (SRD) in optic pits remains a
      mystery. Several hypotheses have been proposed that lead to different treatments
      based on the possible mechanisms which explain the occurrence of SRD. The
      literature data about fluorescein angiography mainly concern the angiographic
      aspects of the optic pit itself, and seldom the SRD. We have examined these
      fluorescein angiographic aspects of the SRD. Indocyanine cardiogreen video
      angiography gives new information which question the last etiologic hypothesis.
      METHODS: Nine patients underwent a fluorescein angiography when the SRD was
      discovered. Indocyanine cardiogreen was performed in four patients. RESULTS: In 8
      cases there was hyperfluorescence on the optic pit. In 7 cases in the
      peripapillar space of the SRD. In one of these cases, there was a leakage on the
      temporal margin of the optic nerve. In 8 cases in the SRD: we noticed a late
      minimal hyperfluorescence in the SRD but it already existed in the early
      angiogram. The SRD became hyperfluorescent in arterio-veinous retinal phase. In
      late phases we noticed a well-demarcated area of hyperfluorescence. CONCLUSION:
      These investigations have revealed a permeation problem on the blood-outer
      retinal barrier of the peripapillar space and above all from the edge of optic
      pit. This can have a prognosis value for SRD. The hyperfluorescence in SRD
      remains an enigma and does not allow, as we thought before, to confirm one of the
      etiopathogenic hypotheses. A better acknowledge of indocyane cardiogreen
      angiographic semiology will allow us to explain these aspects in the future.

PMID- 9238473
TI  - [Surgical treatment of astigmatism caused by penetrating keratoplasty using the
      Hanna arcuate keratome].
AB  - PURPOSE: High postkeratoplasty astigmatism is a common postoperative complication
      which can limit the final functional result. Arcuate incisions are a possible
      surgical treatment. They can be performed with the arcuate keratome which
      provides regular incisions. The aim of this study was to evaluate the results
      obtained with this device in the correction of high postkeratoplasty astigmatism.
      METHODS: We retrospectively studied ten eyes operated for high postkeratoplasty
      astigmatism with the Hanna arcuate keratome. Arcuate keratomy procedures were
      performed on the graft button in all. Before surgery, mean uncorrected visual
      acuity was 0.07 +/- 0.05. Best spectacle-corrected visual acuity was 0.33 +/-
      0.20 and mean subjective cylinder was 6.1 +/- 1.71 D. RESULTS: After one month
      postoperatively, the mean best spectacle-corrected visual acuity (0.45 +/- 0.20)
      was significantly improved (p < 5%) and mean subjective cylinder (2.85 +/- 1.29
      D) was significantly decreased (p < 5%). Vector analysis showed a 5.59 D (+/-
      3.63) mean astigmatism correction. Modifications of the spherical equivalent were
      not statistically significant. Astigmatism irregularity was not modified.
      CONCLUSION: Arcuate keratotomy carried out with the Hanna arcuate keratome is
      effective in reducing high postkeratoplasty astigmatism. It is easier to perform
      than the standard manual technique. However, astigmatism correction
      predictibility should be improved.

PMID- 9238475
TI  - [Posterior scleral reinforcement surgery].
AB  - Scleral reinforcement is proposed to stabilize the visual acuity in patients with
      macular myopic staphyloma. Although many patients have been treated, this
      procedure is still debated. PURPOSE: Evaluation of the feasibility of scleral
      reinforcement and the operative risk of this procedure. PATIENTS AND METHODS:
      Patients were eligible for this prospective study patients with a clinical
      history of visual loss, staphyloma concerning the macular area associated with
      atrophic lesion and or lacquer cracks. Sixteen eyes in 13 successive patients
      have been operated on with a single band of PTFE. RESULTS: At the last
      examination, visual acuity was unchanged for 14 cases. In one case, an
      improvement of the vision was related to the disappearing of a macular detachment
      by shortening of the axial length. In one case, vision decline was associated
      with inadequate band position. Diplopia occurred in 2 cases. A choroidal
      detachment, and a vitreous haemorrhage disappeared without sequelae. CONCLUSION:
      An accurate technique is necessary to avoid operative risk. Further long term
      studies are needed to assess the benefit of scleral reinforcement.

PMID- 9238476
TI  - [Bouchut's tubercles. Clinical and angiographic study, apropos of a case].
AB  - We report a case of miliary tuberculosis in an 11-year-old child, with
      phlyctenular keratoconjunctivitis and choroidal tubercles in both fundi.
      Fluorescein angiography showed early hypofluorescence and late moderate
      hyperflorescence associated with a disseminated choroidis. The presence of these
      lesions supported diagnosis of tuberculosis in our patient because of their
      typical clinical and angiographic aspects.

PMID- 9238477
TI  - [A case of Waardenburg-Klein syndrome observed at the Cotonou NUHC].
AB  - Waardenburg-Klein syndrome is an "Oculo-dermato-auditif" dysplasia described in
      1947 by Waardenburg and by Klein in 1950. Canthus dystopia and congenital
      deafness are the main symptoms. Three clinical types have been reported: type I:
      presents the full symptomatology; type II: without canthus dystopia; type III:
      presents not only the complete syndrome but also an orthro-osteomyodysplasia of
      the upper limbs. This clinical case in a small 3.5-year-old boy with congenital
      deafness, bilateral iris hypochromia and retina albinism without canthus dystopia
      was classed as type II Waardenburg-Klein syndrome. The patient had a second
      apparently fortuitous hereditary affection: hemoglobinopathy (Hb AS). But this
      seems to be fortuitous.

PMID- 9238478
TI  - [Tyndall automatized photometry (PAT) in ophthalmology].

PMID- 9238479
TI  - [Choroidal angioma and Sturge-Weber syndrome].

PMID- 9238480
TI  - Functional neuroimaging. Optical approaches.
AB  - Optical methods assess different types of light tissue interactions such as light
      absorption, fluorescence, phosphoresence, scattering, and Doppler shift. In this
      article, it is reviewed how these different types of light-tissue interactions
      can be measured and how these measurements can be related to brain function.
      Based on these considerations, a new classification scheme of functional optical
      methods is proposed.

PMID- 9238481
TI  - Signal sources in bold contrast fMRI.

PMID- 9238482
TI  - The MRT1 based perfusion model.
AB  - There are a number of theoretical and practical questions one needs to consider
      to understand and optimize contrast to noise of the versatile T1 based perfusion
      model. We made an evaluation of the several popular T1 based methods currently
      applied to measure flow and flow change.

PMID- 9238483
TI  - Is there a different type of MR-contrast in the early phase of functional
      activation?

PMID- 9238484
TI  - Signal sources in PET.

PMID- 9238485
TI  - Can we measure correlates of neuronal activity with non-invasive optical methods?

PMID- 9238487
TI  - Spatial resolution enhancement through time gated measurements.

PMID- 9238486
TI  - Measurement of cytochrome oxidase redox state by near infrared spectroscopy.

PMID- 9238488
TI  - Towards near-infrared imaging of the brain.

PMID- 9238489
TI  - Cerebral oxygenation states as revealed by near-infrared spectrophotometry.

PMID- 9238490
TI  - Brain oxygenation monitoring during cardiopulmonary bypass by near infrared
      spectroscopy.

PMID- 9238491
TI  - A role for near infrared spectroscopy in psychiatry?

PMID- 9238492
TI  - Near-infrared spectroscopy in functional activation studies. Can NIRS demonstrate
      cortical activation?

PMID- 9238493
TI  - Correlation between absolute deoxyhaemoglobin [dHb] measured by near infrared
      spectroscopy (NIRS) and absolute R2' as determined by magnetic resonance imaging
      (MRI).

PMID- 9238494
TI  - Towards brain mapping combining near-infrared spectroscopy and high resolution 3D
      MRI.

PMID- 9238495
TI  - Assessment of local brain activation. A simultaneous PET and near-infrared
      spectroscopy study.
AB  - In five healthy human subjects, near-infrared spectroscopy (NIRS) and positron
      emission tomography (PET) examinations were performed simultaneously. Changes in
      [oxy-Hb], [deoxy-Hb] and [total-Hb] as measured by NIRS over the left forehead
      were compared to measurements of cerebral blood flow by PET during rest and
      during performance of a calculation task and a Stroop task. When a penetration
      depth of near-infrared light 0.9 cm into the brain cortex was assumed, a
      statistically significant correlation between changes in CBF and changes in
      [total-Hb] was found. These data confirm the validity of NIRS measurements in
      human adults.

PMID- 9238496
TI  - Metabolic aspects of neurovascular coupling.

PMID- 9238497
TI  - Metabolic coupling during activation. A cellular view.

PMID- 9238498
TI  - Neuronal-vascular coupling. A unifying hypothesis.

PMID- 9238499
TI  - Understanding functional neuroimaging methods based on neurovascular coupling.
AB  - Functional neuroimaging techniques are usually grouped according to the employed
      apparatus into functional magnetic resonance imaging techniques (fMRI), nuclear
      medicine approaches such as single photon emission tomography (SPET) or positron
      emission tomography (PET), and optical approaches (measurement of intrinsic
      signals, near infrared spectroscopy (NIRS)). However, the physiological
      parameters that are measured with these methods do not necessarily follow this
      technical classification. On the one hand, using different imaging modalities the
      same physiological parameters are measured and on the other hand, using the same
      imaging devices completely different physiological parameters can be assessed.
      The present article covers those functional neuroimaging methods which measure
      the vascular response to functional brain activation (PET, SPET, fMRI and NIRS).
      First, starting with the traditional grouping of these methods, it is outlined
      how the specific methods assess vascular changes associated with brain activation
      in order to localize brain function. Based on the understanding of the underlying
      physiological events, subsequently, a new classification of functional
      neuroimaging methods is proposed.

PMID- 9238501
TI  - Changes of blood flow and oxygen consumption in visual cortex of living humans.

PMID- 9238500
TI  - Dynamic NMR studies of perfusion and oxidative metabolism during focal brain
      activation.
AB  - Together, the present results on oxygenation, flow, and metabolism indicate that
      the prevalence of nonoxidative glycolysis and associated lactate production
      during the initial phase of activation is replaced by the upregulation of
      oxidative glucose consumption (see sketches in Fig. 5). Following rapid
      circulatory changes the gap between oxygen availability and oxygen consumption
      gradually closes until a recoupling of perfusion and oxidative metabolism is
      achieved a few minutes after switching the state of neural activity. While brain
      glucose and lactate concentrations reflect an initial prevalence of anaerobic
      glycolysis, the changes in blood oxygenation suggest that the rapid adjustment of
      blood flow (enhanced oxygen delivery) is followed by a slower upregulation of
      oxidative metabolism (enhanced oxygen consumption). The physiological uncoupling
      of perfusion and oxidative metabolism emerges as a transient phenomenon in
      response to both onset and end of stimulation. Recoupling at enhanced cerebral
      metabolic rates of oxygen (CMRO2) and glucose occurs a few minutes after
      switching the state of neural activity. Since glycolysis takes place primarily in
      astrocytes, the stimulus-related increase and decrease of lactate seen here may
      reflect a transfer of astrocytic lactate to neurons where it is converted into
      pyruvate and channelled into oxidative phosphorylation. This model of metabolic
      responses to functional activation is supported by a recently detected pathway
      for glutamate-stimulated glycolysis in astrocytes that provides a simple
      mechanism linking astrocytic glucose utilization to neuronal activity (Pellerin
      and Magistretti, 1994). In summary, evidence has accumulated that the
      physiological uncoupling of perfusion and oxidative metabolism associated with
      the onset of functional activation is a transient phenomenon leading to an only
      temporal mismatch of oxygen delivery and consumption. Recoupling at enhanced
      though balanced levels of glucose and oxygen consumption is most remarkably
      documented by the pronounced "negative" uncoupling at the end of stimulation.

PMID- 9238502
TI  - Uncoupling of absolute CBF to neural activity.

PMID- 9238503
TI  - Vascular regulation at sub millimeter range. Sources of intrinsic signals for
      high resolution optical imaging.

PMID- 9238504
TI  - Linking cerebral blood oxygenation to human brain function. Current issues for
      human neuroscience by magnetic resonance neuroimaging.

PMID- 9238505
TI  - Intersubject analysis of fMRI data using spatial normalization.

PMID- 9238506
TI  - What do we expect from non-invasive functional neuroimaging?

PMID- 9238507
TI  - NF-IL6 and NF-kappa B in cytokine gene regulation.

PMID- 9238508
TI  - Transporter associated with antigen processing.

PMID- 9238509
TI  - NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory
      molecules.

PMID- 9238510
TI  - Mouse mammary tumor virus: immunological interplays between virus and host.

PMID- 9238511
TI  - IgA deficiency.

PMID- 9238512
TI  - Role of cellular immunity in protection against HIV infection.

PMID- 9238513
TI  - High endothelial venules: lymphocyte traffic control and controlled traffic.

PMID- 9238514
TI  - Genetic variation at structural loci in the Glossina morsitans species group.
AB  - Gene diversity was investigated in four taxa of tsetse flies (Diptera:
      Glossinidae) including Glossina morsitans, G.m. centralis, G. Swynnertoni, and G.
      pallidipes. Histochemical tests were performed for 35-46 isozymes. Polymorphic
      loci were 20% in G. morsitans, 32% in G.m. centralis, 17.6% in G. swynnertoni,
      and 26% in G. pallidipes. Mean heterozygosities among all loci were 6.6% in G.
      morsitans morsitans, 6.0% in G.m. centralis, 7.1% in G. swynnertoni, and 6.8%
      pallidipes. Allozyme gene diversities were considerably less than those reported
      for many Diptera. The low gene diversities are probably related to small
      effective population sizes.

PMID- 9238515
TI  - Genetic diversity and divergence in Chinese yak (Bos grunniens) populations
      inferred from blood protein electrophoresis.
AB  - In 6 Chinese yak (Bos. grunniens) populations including 177 yaks, 34 blood
      protein loci were studied by horizontal starch gel electrophoresis, four of these
      loci (AKP, ALB, LDH-1, TF) were found to be polymorphic. The percentage of
      polymorphic loci(P) is 0.118, the mean individual heterozygosity(H) is 0.015,
      which means a low level of genetic diversity in the whole Chinese yak population.
      The coefficient of gene differentiation (Gst) is 0.0625, which indicated an
      almost-indistinguishable divergence among different populations at the level of
      blood protein electrophoresis.

PMID- 9238516
TI  - Biochemistry of esterases associated with organophosphate resistance in Lucilia
      cuprina with comparisons to putative orthologues in other Diptera.
AB  - Esterase activities associated with organophosphate insecticide resistance in the
      Australian sheep blowfly, Lucilia cuprina, are compared with similar activities
      in other Diptera. The enzymes making the major contribution to methyl butyrate
      hydrolysis ("ali-esterase") in L. cuprina, M. domestica, and D. melanogaster
      comigrate during electrophoresis. The enzymes in L. cuprina and D. melanogaster
      correspond to the naphthyl acetate hydrolyzing E3 and EST23 isozymes of those
      species. These and previously published data suggest that the ali-esterases of
      all three species are orthologous. Strains of L. cuprina fall into four groups on
      the basis of quantitative determinations of their ali-estesterase, OP hydrolase,
      and malathion carboxylesterase activities and these groups correspond to their
      status with respect to two types of OP resistance. Strains susceptible to OP's
      have high ali-esterase, low OP hydrolase, and intermediate MCE activities; those
      resistant to malathion but not diazinon have low ali-esterase, intermediate OP
      hydrolase, and high MCE activities; those resistant to diazinon but not malathion
      have low ali-esterase, high OP hydrolase, and low MCE activities; those resistant
      to both OPs have low ali-esterase, high OP hydrolase, and high MCE activities.
      The correlated changes among the three biochemical and two resistance phenotypes
      suggest that they are all properties of one gene/enzyme system; three major
      allelic variants of that system explain OP susceptibility and the two types of OP
      resistance. Models are proposed to explain the joint contribution of OP hydrolase
      and MCE activities to malathion resistance and the invariant association of low
      ali-esterase and elevated OP hydrolase activities in either type of resistance.

PMID- 9238517
TI  - Genetic variants affecting phenoloxidase activity in Drosophila melanogaster.
AB  - In Drosophila melanogaster, two new variants affecting the activity of
      phenoloxidase were found in natural populations at Gomel in Belorussia and at
      Krasnodar in Russia. Prophenoloxidases, A1 and A3, in these variants had the same
      mobilities on native electrophoresis as the wild type. However, enzymatic
      activities in their activated states were much lower than in the wild type,
      whereas the existence of prophenoloxidase proteins was demonstrated. Egg-to-adult
      and relative viabilities in the variants did not decrease at temperature between
      18 and 29 degrees C. Genetic analyses indicated that the genes showing the
      phenotype of variants are new alleles of Mox and Dox-3 on the second chromosome.

PMID- 9238518
TI  - Comparison of the subcellular distribution of the messages encoding PLP and DM
      20.
AB  - Oligonucleotides provide a means to differentiate between closely related mRNAs.
      Here in situ hybridization is performed using oligonucleotide probes to determine
      the subcellular distribution of two differential splicing products of a single
      gene. It is demonstrated here that the subcellular distributions of PLP and DM-20
      messages in oligodendrocytes are quite different, despite being transcripts of a
      single gene.

PMID- 9238519
TI  - The glycophorin A gene family in gorillas: structure, expression, and comparison
      with the human and chimpanzee homologues.
AB  - Homologues of MN blood group antigens, encoded by members of the glycophorin A
      (GPA) gene family, are expressed in man, anthropoid apes, and some species of Old
      World monkeys. Previous studies had shown that a three-gene framework, most
      closely related to that in man, is present in the chimpanzee. Here we report the
      genomic structure, transcript map, and protein expression of the GYPA locus in
      gorillas. Compared to the corresponding human and chimpanzee homologues, gorilla
      GPA, GPB, and GPB/E genes each showed a high degree of sequence identity, with
      the same exon-intron organization. However, the expression of exons III, IV or V
      encoding the extracellular or membrane domains of homologous glycophorins varied
      among the three species. Gorilla GPA and GPB/E genes were unique in that the
      former occurred in two allelic forms with or without the expression of exon III,
      whereas the latter contained one (psi exon III) instead of two silenced exons
      (psi exons III and IV). Differences from human but not chimpanzee GPA also
      included the presence of a hybrid M/N epitope and the absence of the sequon for N
      glycosylation. Owing to the retention of a functional exon III, gorilla GPB was
      more similar to chimpanzee GPB than human GPB. A transspecies allele was
      identified in the gorilla that gave rise to the Henshaw (He)-like antigen similar
      to that found in man. These results provide further insight into the model for
      evolution of the GPA gene family, indicating that the mechanisms underlying inter
      and intraspecific polymorphism of glycophorins could predate the divergence of
      gorillas as the consequence of gene duplication and diversification.

PMID- 9238521
TI  - Effect of sevin on kinetic parameters of camel retina acetylcholinesterase.
AB  - The present investigation addresses the effect of sevin (insecticide) on kinetic
      parameters of camel retina membrane-bound acetylcholinesterase (AChE, EC
      3.1.1.7). The Michaelis-Menten constant (Ks) for the hydrolysis of
      acetylthiocholine iodide (ASCh) by AChE was 0.072 mM in the control system, a
      value decreased by 38-55% in the sevin treated systems. The Vmax was 0.967
      mumole/min/mg protein for the control system while it was decreased by 50-84% in
      the sevin treated systems. The Lineweaver-Burk plot, Dixon plot, and their
      secondary replots indicated that the nature of the inhibition was of the linear
      mixed type, i.e. uncompetitive and noncompetitive. The values of Ki(slope) and
      KI(intercept) were estimated as 6.194 and 2.811 microM, respectively. The
      turnover number (Kcat) and specificity constant (Ksp) were 74.65 min-1 and 10.37
      x 10(5) (M.min)-1 in the control system respectively, while the values for both
      parameters were significantly decreased in the sevin treated systems.

PMID- 9238520
TI  - Differential expression of multiple cathepsin mRNAs in the rat testis during
      maturation and following lonidamine induced tissue restructuring.
AB  - In the seminiferous epithelium, germ cell development behind the blood-testis
      barrier involves continual degradation and renewal of inter-testicular cell
      junctions. This allows: (i) the translocation of developing germ cells from the
      basal lamina to the adluminal compartment during spermatogenesis, and (ii) the
      eventual release of mature spermatids into the tubular lumen during spermiation.
      Throughout spermatogenesis, cellular debris must also be removed from the
      epithelium Thus, it is conceivable that proteases, protease inhibitors, and cell
      junctional components are involved in these events. The present study sought to
      examine whether testicular cells can express multiple cathepsin mRNAs given that
      these proteases are involved in the degradation and processing of proteins as
      well as in tissue regeneration. By using total RNA isolated from primary cultures
      of Sertoli, Leydig, and germ cells for reverse-transcription and polymerase chain
      reaction (RT-PCR), the mRNAs of cathepsin B, C, D, H, L, and S were shown to be
      expressed by Sertoli and Leydig cells, whereas germ cells isolated from adult
      rats expressed all of the above cathepsin mRNAs except cathepsin D. Throughout
      postnatal development and maturation, the testicular steady-state mRNA levels of
      cathepsin B, C, D, L, and S remain relatively unchanged with the exception of
      cathepsin H whose mRNA level increased during maturation and peaked at 45-60 days
      of age. Using lonidamine, an anti-spermatogenic drug which is known to induce
      premature release of germ cells without affecting Leydig cell function by
      disrupting the inter-Sertoli-germ cell junctions, we have examined the
      differential expression of these cathepsin mRNAs in the testis at the time of
      extensive tissue restructuring. It was noted that the expression of cathepsin L
      and S in the testis increased significantly concomitant with the disappearance of
      elongate spermatids whereas the expression of cathepsin B, C, D, and H increased
      significantly when most of the round spermatids and spermatocytes were depleted.
      These results illustrate the intricate inter-relationship between these proteases
      in the testis during maturation and tissue restructuring.

PMID- 9238522
TI  - Gastric mucosal apoptosis induced by ethanol: effect of antiulcer agents.
AB  - In this study, we investigated gastric epithelial cells' apoptosis and tumor
      necrosis factor-alpha (TNF-alpha) expression with ethanol-induced mucosal injury,
      and the effect of antiulcer agents on this process. Rats received intragastric
      pretreatment with the agent or vehicle followed 1h later by ethanol, and after 30
      min the gastric mucosa was assessed for TNF-alpha and apoptosis. In the absence
      of antiulcer agents, ethanol caused extensive mucosal lesions accompanied by a
      9.5-fold enhancement in apoptosis and a 2.5-fold increase in TNF-alpha.
      Pretreatment with omeprazole evoked a 54% reduction in TNF-alpha, but had no
      effect on ethanol-induced mucosal damage or apoptosis, the sucralfate reduced the
      extent of mucosal damage by 95%, apoptosis by 39% and TNF-alpha by 52%, while
      ebrotidine not only prevented mucosal injury and rise in TNF-alpha, but also
      caused a 70% reduction in epithelial cells' apoptosis. The results demonstrate
      that ethanol-induced gastric epithelial cells apoptosis triggered by the
      enhancement in mucosal TNF-alpha is efficiently counteracted by ebrotidine.

PMID- 9238523
TI  - cDNA-derived amino-acid sequence of a land turtle (Geochelone carbonaria) beta
      chain hemoglobin.
AB  - The cDNA sequence encoding the turtle Geochelone carbonaria beta-chain was
      determinated. The isolation of hemoglobin mRNA was based on degenerate primers'
      PCR in combination with 5'- and 3'-RACE protocol. The full length cDNA is 615 bp
      with the ATG start codon at position 53 and TGA stop codon at position 495; The
      AATAAA polyadenylation signal is found at position 599. The deduced polypeptyde
      contains 146 amino-acid residues. The predicted amino acid sequence shares 83%
      identity with the beta-globin of a related specie, the aquatic turtle C. p.
      belli. Otherwise, identity is higher when compared with chicken beta-Hb (80%)
      than with other reptilian orders (Squamata, 69%, and Crocodilia, 61%). Compared
      with human HbA, there is 67% identity, and at least three amino acid
      substitutions could be of some functional significance (Glu43 beta-->Ser, His116
      beta-->Thr and His143 beta-->Leu). To our knowledge this represents the first
      cDNA sequence of a reptile globin gene described.

PMID- 9238524
TI  - Amino acid metabolism in the kidneys of genetic and nutritionally obese rats.
AB  - The ability of the kidney to take up and/or release amino acids has been
      determined in two models of obesity in Zucker rats, one genetic and the other
      nutritional (diet-obese). There was a noticeable increase in gluconeogenic amino
      acids in the arterial blood of diet-obese animals whereas the genetically obese
      rats showed small variations in the levels of these amino acids. There were
      significant decreases in renal Gly and Ser, only in the genetically obese rats.
      Genetically obese animals showed an increase in Glutamine synthetase activity.
      The uptake and/or release of amino acids showed important variations between the
      groups. The diet-obese group exhibited greater variation, since this group took
      up Glu, Ala, Gy, Phe and Citrulline and released Gln, Ser, Arg and Tyr.
      Genetically obese rats took up Gln, His and Taurine and released Ser. These
      different patterns may be related to variations in the whole body metabolic rate,
      since the diet-obese group was more active than the genetically obese group.

PMID- 9238525
TI  - Menadione-dependent reduction of tertiary amine N-oxide by rat liver cytosol.
AB  - This study demonstrates the menadione-dependent reduction of imipramine N-oxide,
      a tertiary amine N-oxide, to imipramine by rat liver cytosol in the presence of
      NADH or NADPH. A mechanism for the cytosolic reduction of the tertiary amine N
      oxide is proposed. Menadione is converted to its reduced form by a menadione
      reducing enzyme such as DT-diaphorase and the reduced pyridine nucleotide,
      followed by reduction of the tertiary amine N-oxide to the amine by the heme
      group of catalytic hemoproteins in the presence of reduced menadione as an
      electron donor.

PMID- 9238526
TI  - Effect of thiols on fructosamine assay.
AB  - Fresh human serum, gGAPDH and beta-mercaptoethanol were used to examine the
      effect of thiols on fructosamine assay. The kinetics of the reaction with both
      fresh human serum and gGAPDH displayed biphasic behaviour (fast and slow). When
      the thiols were modified with IAA, the kinetics only demonstrated the slow phase.
      Since the absorbance increase in the interval from 9 to 10 min was used in the
      fructosamine assay of glycated human serum we studied the effect of thiols on
      that measurement. In the case of gGAPDH, the value was approximately one-half of
      the original after thiol modification, suggesting thiol interference.
      Nevertheless, gGAPDH may contain a fructosamine structure. beta-Mercaptoethanol
      itself gave a strong positive result in the fructosamine assay. Hence, thiol
      groups on glycated proteins should be modified before doing a fructosamine assay
      because of their substantial interference.

PMID- 9238527
TI  - Ageing-associated large-scale deletions of mitochondrial DNA in human hair
      follicles.
AB  - Hair follicles plucked from the bi-temporal region of the scalp of 433 Chinese
      subjects of different ages were used for the examination of ageing-associated
      mutations of human mitochondrial DNA (mtDNA). By use of PCR techniques, we
      detected the 4,977 bp and 7,436 bp deletions of mtDNA in hair follicles from aged
      individuals. The frequencies of occurrence of both mtDNA deletions were found to
      increase with age of the subject. Moreover, we employed a semi-quantitative PCR
      method to determine the proportion of the 4,977 bp deleted mtDNA (dmtDNA) in hair
      follicles. The results showed that the average proportion of the 4,977 bp dmtDNA
      in hair follicles were 0.05% +/- 0.01%, 0.00%, 0.55% +/- 0.05%, 0.52% +/- 0.24%,
      0.65% +/- 0.17%, 1.33 +/- 0.25%, and 1.89% +/- 0.81% for the subjects in the age
      groups of 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, and 81-99, respectively.
      Furthermore, we screened all the subjects harboring the 4,977 bp and/or 7,436 bp
      deletions for tandem duplications in the D-loop region of mtDNA by PCR with back
      to-back primers. The results showed that none of the previously reported tandem
      duplications were present in all the hair follicles examined. This indicates that
      tandem duplications do not predispose to large-scale deletions of mtDNA. However,
      the data suggest that mtDNA deletions occur and accumulate in hair follicles
      during human ageing. As hair follicles can be easily and non-invasively obtained
      from the human, we suggest that the aged-dependent accumulation of dmtDNAs in
      hair follicles may be used for the monitoring of human ageing process.

PMID- 9238528
TI  - Activity and carboxylation specificity factor of mutant ribulose 1,5-bisphosphate
      carboxylase/oxygenase from Anacystis nidulans.
AB  - The values of molecular carboxylase activity kcat and carboxylation specificity
      factor tau for mutant ribulose 1,5-bisphosphate carboxylase (rubisco) from
      Anacystis nidulans decreased as compared to those of the wild type recombinant
      rubisco. The substitution of five amino acid residues in rubisco large subunit
      Lys,Ala,Ser,Thr,Leu(339-343)Phe,Leu,Met,Ile,Lys had kcat decreased by 90% and tau
      by 36.3%. The same parameters for mutants with the single replacements decreased:
      for Thr342Ile kcat by 40.5% and tau by 16.7%, and for mutant Leu343Lys kcat by
      48.1% and tau by 18.5%. Mutant rubisco with three amino acid residues changed
      Val,Asp,Leu(346-348)Tyr,His,Thr was inactive. The substitution Leu326Ile
      decreased kcat by 54.4% and tau by 34.2%; and change Ser328Ala decreased kcat
      only by 5.6% but tau by 41.5%. Replacement Asn123His decreased kcat by 16.5%.
      Significance of the non conservative amino acid residues for carboxylase activity
      and ribulose-1,5-bisphosphate partition is discussed.

PMID- 9238529
TI  - Isolation of the transferrin receptor from human placenta.
AB  - The transferrin receptor (TFR) has been detected in tissues characterised by a
      high degree of proliferation. We have developed a procedure for isolating TFR
      from human placental tissues by affinity chromatography on transferrin-Sepharose.
      Using gel filtration and electrophoresis in 7% PAAG, it has been shown that the
      molecular mass of the protein is 180 kDa. The protein has a subunit structure and
      is made up of two identical subunits, 90 kDa each. The constant for the protein
      binding to transferrin is equal to 5 x 10(-9) M. The yield of the protein
      isolated by the novel procedure exceeds 5-fold that obtained by previously
      described methods.

PMID- 9238531
TI  - Expression of soluble, active human macrophage colony stimulating factor in
      Escherichia coli.
AB  - Human macrophage colony stimulating factor (M-CSF) has been successfully
      overexpressed in Escherichia coli AD494 (DE3) with an expression level of
      approximate 26% of the total cellular proteins. The truncated human M-CSF gene
      encoding the amino-terminal 149 amino acids was subcloned into the prokaryotic
      expression vector pET11d under the control of the inducible T7 promoter. Nearly
      40% of the recombinant protein was in the soluble fraction which showed obvious
      stimulating effects on mouse macrophage colony formation and had an M-CSF
      specific activity of approximately 1 x 10(6) units/mg soluble protein.

PMID- 9238530
TI  - Glucose transport in a murine mammary epithelial cell line.
AB  - The glucose transport systems of the COMMA-D cell line (a murine mammary
      epithelial cell line) were examined using 2-deoxyglucose as substrate. The
      kinetics and inhibition studies with other sugars including xylose suggested that
      the transport system had properties of both GLUT-1 and Glut-3. Subsequent
      analysis of mRNA transcripts using cDNAs for GLUT-1 to 4 showed that only GLUT-1
      was expressed in the COMMA-D cells. The results highlight the fact that kinetic
      and substrate specificity are not sufficient, by themselves, for the
      identification and characterisation of GLUT isoforms in cultured cells.

PMID- 9238532
TI  - Variable requirement for splicing signals for nucleocytoplasmic export of mRNAs.
AB  - Using in situ hybridisation to detect the intracellular localisation of mRNAs we
      have found that mRNAs expressed from intronless cDNAs of normally intronic genes
      are expressed well but largely retained in nuclei. The degree of nuclear
      retention is quite variable but in all cases addition of splicing signals to the
      expression cassette are required for efficient export of the mRNAs from nucleus
      to cytoplasm. In contrast mRNAs expressed from the intronless genes of hamster
      beta-adrenergic receptor and human serotonin receptor type 1A showed very little
      nuclear accumulation and strong expression in the cytoplasm independently of
      splicing signals. The data demonstrate a link between splicing and export and
      dissemble from the idea that splicing enhances mRNA expression by protecting
      nascent nuclear mRNAs from degradation.

PMID- 9238533
TI  - Effect of vitamin D deficiency on lipid composition and calcium transport in
      basolateral membrane vesicles from chick intestine.
AB  - Vitamin D deficiency affects the lipid composition and Ca2+ uptake of intestinal
      basolateral membranes from chick intestine. The increased cholesterol content
      causes an increase in the molar ratio cholesterol/phospholipid. Phospholipid
      classes remain unchanged, but the percentages of arachidonic acid from the from
      the major phospholipid fractions are increased. After 24 hours of oral
      administration of 2,000 IU of cholecalciferol to vitamin D-deficient chicks, the
      cholesterol values do not change, but the amount of arachidonic acid returns to
      normal values. Ca2+ uptake driven by ATP is diminished in vesicles from
      intestinal basolateral membranes of vitamin D-deficient chicks. Cholecalciferol
      treatment returns these values to the controls which might be due mainly to the
      increased number of Ca2+ pump units. In conclusion, changes in lipid composition
      and in Ca2+ pump caused by vitamin D deficiency seems to play a role in the
      decrease of vesicular Ca2+ transport. A single dose of cholecalciferol restores
      only partially the lipid-protein changes produced by vitamin D deficiency.

PMID- 9238534
TI  - Use of an automated sequencer to determine the sequence specificity of DNA
      damage.
AB  - An automated sequencer was used to determine the sequence specificity of DNA
      damage caused by hedamycin in the plasmid pUC19 using a linear amplification/Taq
      DNA polymerase method. Previously, manual DNA sequencers have been in widespread
      use to investigate the sequence specificity of a DNA damaging agent. Manual DNA
      sequencers are restricted in the length of DNA sequence that can be read at base
      pair resolution for densitometry. An automated sequencer can greatly expand on
      the length of analysable DNA sequence. An additional important capability of the
      automated sequencer, is the ability to quantitate the intensity of damage at each
      base pair site. Thus we have used the automated sequencer to elucidate the
      sequence specificity of DNA damage for 300 bp. We have carried out an extended
      analysis of the sequence specificity of hedamycin DNA damage and found that the
      sequence 5'-cGt-3', tGt and cGg are preferentially damaged. The sequence
      specificity of cisplatin was also investigated.

PMID- 9238535
TI  - Proton-donative antioxidant activity of fucoxanthin with 1,1-diphenyl-2
      picrylhydrazyl (DPPH).
AB  - Reactions between a carotenoid, fucoxanthin and 1,1-diphenyl-2-picrylhydrazyl
      were investigated both under anoxic and aerobic conditions. Fucoxanthin
      equimolarly reacted with 1,1-diphenyl-2-picrylhydrazyl under anoxic conditions.
      Under aerobic conditions, only a part of fucoxanthin consumed 1,1-diphenyl-2
      picrylhydrazyl and the degree of reaction fluctuated with repeated trials. beta
      Carotene or other carotenoids, beta-cryptoxanthin, zeaxanthin, licopen and
      lutein, were also examined in the reaction with 1,1-diphenyl-2-picrylhydrazyl
      under anoxic conditions. All these compounds scarcely reacted with 1,1-diphenyl-2
      picrylhydrazyl.

PMID- 9238536
TI  - Role of H-ras gene in chronic liver damage in mice. By using transgenic mice
      carrying a human C-H-ras proto-oncogene without mutations.
AB  - Hepatic tumors including hepatocellular carcinoma were generated by carbon
      tetrachloride in transgenic mice carrying a human c-H-ras gene (rasH2 mice).
      RasH2 mice express 2 to 3 times more ras protein (ras p21) in the liver than do
      non-Tg mice. When carbon tetrachloride was administered, the rasH2 mice produced
      about 5 times as many hepatic tumors than did the non-transgenic mice. However,
      neither the 10-100 times higher ras p21 expression required for murine fibroblast
      transformation by itself nor the mutational activation of the H-ras gene was
      observed in carbon tetrachloride-induced hepatic tumors. These results show that
      H-ras proto-oncogene expression in the murine liver, even if it is not high
      enough to transform cells, also causes liver tumors when CC1(4) are repeatedly
      given.

PMID- 9238537
TI  - Partial restoration of inactivated ribosomes: role of the aldehyde group
      generated by RNA N-glycosidase in the sarcin/ricin domain of 28S rRNA in
      ribosome.
AB  - In this paper, we report more information on the important role of the aldehyde
      group in the sarcin/ricin domain of 28S rRNA in rat liver ribosome. We find D
      amino acids, amino acid derivatives having free amino group and two polyamines
      can also partially restore the activity of cinnamomin-inactivated ribosomes.
      However, amino acid derivatives and a tripeptide with blocked amino group cannot.
      Neither sodium borohydride nor the L-amino acids can restore the activity of
      ribosomes inactivated by alpha-sarcin. These data demonstrate that partial
      restoration of the activity of the inactivated ribosome is indeed the result of
      the blockage of the aldehyde group. It reaches the conclusion that emergence of
      the active aldehyde group in the sarcin/ricin domain of 28S rRNA is one of
      factors that inactivate the ribosome for protein synthesis.

PMID- 9238538
TI  - Nitroaromatic betulin derivatives as redox cycling agents.
AB  - We have synthesized nitroaromatic derivatives of triterpenoid betulin (lup-20(29)
      ene-3 beta, 28-diol), betulin-(28)-5'-(aziridin-1-yl)-2',4'-dinitrobenzoate and
      betulin-(28)-5'-nitro-2'-furoate. These compounds were reduced in single-electron
      way by ferredoxin: NADP+ reductase and flavocytochrome b2 at rates comparable
      with their simple structure analogs. Besides, these compounds were substrates for
      DT-diaphorase. Their toxicity to bovine leukemia virus-transformed lamb
      fibroblast culture was partly prevented by antioxidant N,N'-diphenyl-p-phenylene
      diamine and desferrioxamine, indicating an involvement of oxidative stress in
      their cytotoxicity.

PMID- 9238539
TI  - Determination of sugar specificity of jackfruit lectin by a simple sugar-lectin
      binding assay using microtiter plate.
AB  - Sugar-lectin binding assay was developed as a simple method which employed direct
      coating of microtiter plate with galactose-binding lectins. Biotin-galactose
      conjugate was used to bind to the immobilized lectins. The bound conjugate was
      then detected using streptavidin-horseradish peroxidase. Using the assay in
      conjunction with various competing carbohydrates, jackfruit lectin from
      Artocarpus heterophyllus was found to be specific for alpha-anomer of galactoside
      with an aromatic residue.

PMID- 9238540
TI  - Cloning, expression and purification of the coat protein of encephalitis virus
      (DIEV) infecting Dicentrarchus labrax.
AB  - The coat protein gene from encephalitis virus infecting Dicentrarhus labrax
      (DIEV) has been cloned by gene amplification, sequenced and expressed in
      Escherichia coli. DNA sequencing has revealed an open reading frame of 1017 bases
      encoding a polypeptide of 338 amino acids. The sequence similarities between the
      DIEV coat protein gene and the same gene in five encephalitis viruses infected
      other fish species were over 71.5% at the nucleotide level and over 79.5% at the
      amino acid level. These results indicate that the nodaviruses that cause
      encephalopathy and retinopathy in fishes are very closed related. E. coli cells
      harbouring the plasmid containing the DIEV gene can produce the viral coat
      protein. An efficient purification scheme using a Sepharore-Ni+2 column is
      presented. This, gives approx. 10 mg of more than 95% pure protein per gr of E.
      coli culture.

PMID- 9238541
TI  - Effect of 5-fluorouracil on interleukin-1 and interleukin-2 receptor expression.
AB  - We have studied the effect of anticancer drug 5-fluorouracil on the expression of
      human Interleukin-1 and Interleukin-2 receptor. In this report, we show that 5
      Fluorouracil increases the Interleukin-1 expression upto 2.66 folds without
      significantly affecting the levels of surface expression of p55 IL-2 receptor on
      human Peripheral blood mononuclear cells, CD4 and CD8 T cells. On contrary, the
      drug decreases the levels of Interferon-gamma secretion by upto 42%. In earlier
      studies we have shown that 5-fluorouracil increases the IL-2 expression both at
      mRNA and protein levels. Taken together, 5-fluorouracil differentially affects
      the expression of Interleukin-1, Interferon-gamma and Interleukin-2 receptor.

PMID- 9238542
TI  - Expression of the trefoil polypeptide ITF in PC12 cells.
AB  - Trefoil polypeptides are expressed mainly in the amphibian skin and the
      gastrointestinal tract of mammals, usually coexpressed with mucin-glycoproteins.
      Recently, the trefoil polypeptides were shown to be expressed also in different
      areas of the human and murine brain. To investigate the expression and possible
      functions of ITF in rat pheochromocytoma (PC12) cells were employed. PC12 cells
      show a low basal expression of this polypeptide as determined by reverse
      transcriptase-polymerase chain reaction. After treatment with the synthetic
      glucocorticoid dexamethasone, the second messenger cyclic adenosine monophosphate
      and the neurotrophic factor nerve growth factor the expression of the trefoil
      polypeptide ITF was increased as shown by reverse transcriptase-polymerase chain
      reaction and by immunocytochemistry. Since these various stimuli can directly can
      directly alter the expression level of this peptide we conclude that the
      presented results may from the basis for further investigations of possible
      functions of this novel gut-brain polypeptide in neurons using PC12 cells.

PMID- 9238543
TI  - The development of the Louis MACRO (Mother and Child Risk Observation) forms:
      assessing parent-infant-child risk in the presence of maternal mental illness.
AB  - OBJECTIVE: The theoretical framework and psychometric properties of the MACRO
      (Mother and Child Risk Observation) 1 and 2 forms (age 0 to 4 year) are
      presented. The MACRO forms provide ratings on five domains--three related to
      parenting, two on infant (or child) characteristics and maternal mental state.
      Case vignettes illustrate their clinical utility. METHOD: Ratings on the MACRO of
      110 mother-infant and 85 mother-toddler consecutive admissions to a South
      Australian psychiatric in-patient mother-infant unit provided data on internal
      consistency, interrater, and test-retest reliability. RESULTS: Internal
      consistency was between .79 and .95 for all MACRO domains. Item-total
      correlations were between .39 and .90 with the exception of one item. Social
      Support. Distributions of item scores indicated acceptable discrimination.
      Interrater reliability was .79 or above for all domains. Test-retest reliability
      after 7 days was .71 or above. CONCLUSIONS: Preliminary psychometric
      investigations of the MACRO was favorable. Should further validity investigations
      prove satisfactory, the MACRO will provide a valuable clinical and research tool.
      The MACRO offers a convenient framework for assessing risk and interpreting the
      impact of maternal mental illness upon children within a context that permits
      consideration of factors such as illness severity, parenting practices, and child
      contribution to outcome.

PMID- 9238544
TI  - Social support in child abuse and neglect: support functions, sources, and
      contexts.
AB  - OBJECTIVES: The objective of the present paper was to examine the social support
      functions, sources and temporal contexts of Argentinian mothers in relation to
      child abuse and neglect. METHOD: To test the impact of social support on child
      abuse and neglect, a sample of 101 Argentinian mothers was drawn from the
      pediatric hospital. The interview contained questions regarding maternal social
      support and abusive behavior. After the interview, the medical record of the
      child was checked for information concerning child abuse and neglect. RESULTS:
      Data from the interview and the medical record were used to characterize the
      mothers as low or high in child abuse and neglect. CONCLUSIONS: Comparisons
      between both groups of mothers indicated that only some specific support indexes
      distinguished mothers with low and high abuse/neglect. Specifically, kin and
      instrumental support indexes were associated with child abuse/neglect, whereas
      nonkin and psychological support variables were not.

PMID- 9238545
TI  - Physical punishment/maltreatment during childhood and adjustment in young
      adulthood.
AB  - OBJECTIVE: To study the relationships between retrospective reports of physical
      punishment/maltreatment and rates of adjustment difficulties at age 18 in a birth
      cohort of New Zealand subjects. METHOD: Data were gathered over the course of an
      18 year longitudinal study of a birth cohort of 1,265 New Zealand born children.
      At age 18 retrospective reports of exposure to physical punishment/maltreatment
      were obtained. At this time the cohort was also assessed on measures of
      psychosocial adjustment juvenile offending, substance abuse behaviors, and
      psychiatric disorder. RESULTS: Young people reporting exposure to harsh or
      abusive treatment during childhood had elevated rates of juvenile offending,
      substance abuse, and mental health problems. However, subsequent analysis using
      logistic regression methods showed that much of the elevated risk shown by this
      group was explained by social and contextual factors that were associated with
      patterns of childhood punishment/maltreatment. Nonetheless, even after control
      for confounding factors those reporting harsh or abusive childhood experiences
      were at increased risks of violent offending, suicide attempts, being a victim of
      violence, and alcohol abuse. CONCLUSION: This study leads to three major
      conclusions: (1) Those exposed to harsh or abusive treatment during childhood are
      an at-risk population for juvenile offending, substance abuse, and mental health
      problems; (2) Much of this elevated risk arises from the social context within
      which harsh or abusive treatment occurs; (3) Nonetheless, exposure to abuse
      appears to increase risks of involvement in violent behavior and alcohol abuse.

PMID- 9238546
TI  - Assessment of coping strategies of child abusing mothers.
AB  - OBJECTIVE: Mothers who had physically abused their children were assessed to
      determine whether these mothers had a general coping skills deficit. METHOD:
      Abusing mothers (n = 17) were compared to nonabusing mothers of conduct problem
      children (n = 16). Coping was measured by several methods, each designed to
      address the insufficiencies of the others. RESULTS: In comparison to the
      nonabusing mothers, independent ratings indicated that abusing mothers exhibited
      a pattern of coping characterized by greater use of emotion-focused coping
      strategies and less use of effective problem-focused strategies. Finally, using
      self report ratings of coping, abusing mothers perceived their coping to be more
      ineffective than the nonabusing mothers. CONCLUSIONS: The possibility that the
      observed coping skills deficit may be indicative of a deficit in emotional
      responding to stress was discussed and suggestions were given for therapeutic
      interventions with child abusing mothers.

PMID- 9238547
TI  - The Challenge Project: a treatment program evaluation for perpetrators of child
      sexual abuse.
AB  - OBJECTIVE: Research on treatment outcome for sex offenders has been poorly
      designed, with biased sampling, lack of controls, and a failure to define
      treatment programs, subjects, and outcome measures. This research aimed to
      compare group and individual treatment outcomes, with particular reference to
      program compliance and reoffending. METHOD: The Challenge Project assessed all 80
      convicted perpetrators of child sexual abuse in S.E. London over a 2-year period,
      and followed them up 1 and 2 years later. The 43 perpetrators who were diverted
      into the community program received weekly standardized cognitive-behavioral
      treatment over a 1-year period. Subjects were matched on key variables and
      entered either group or individual therapy. RESULTS: Some treatment effects could
      be demonstrated in both group and individual therapy, particularly if individual
      changes in test scores were examined. Two variables were significantly associated
      with poor treatment compliance: A history of sexual and/or violent offending, and
      a history of childhood sexual victimization. However, only one subject had been
      convicted of a further sexual offense--possession of child pornography--at follow
      up. CONCLUSION: The findings may support professionals in deciding how best to
      allocate scarce resources; and it is intended to extend the outcome study to at
      least a 5-year follow-up period, to see whether compliance and shifts in
      psychological measures are a valid predictor of outcome.

PMID- 9238548
TI  - The relationship between childhood sexual abuse and adult male sexual
      dysfunction.
AB  - OBJECTIVE: The present study investigated the relationship between childhood
      sexual abuse and adult sexual dysfunction in men. In addition, the investigation
      compared sexually abused men and women on the characteristics of the sexual
      abuse. METHOD: Subjects were 359 men who sought sexual dysfunction treatment.
      Thirty men reported a history of sexual abuse. Characteristics of the sexual
      abuse experienced by these men also were compared to the sexual abuse experienced
      by 73 women initially investigated elsewhere (Sarwer & Durlak 1996). RESULTS:
      Sexual abuse was not found to predict sexual dysfunction in these men. Rather,
      unemployment served as the only significant predictor of male sexual dysfunction.
      Comparisons of the sexual abuse reported by male and female victims indicated
      that males were more likely to experience physical force, but were less likely
      than female victims to be abused more than once and to be abused by an adult.
      CONCLUSIONS: The results support the notion that childhood sexual abuse may not
      be as disruptive to adult sexual functioning in men as it is in women. This
      difference may be a function of the specific circumstances of the sexual abuse.
      Suggestions for future research on male sexual abuse are provided.

PMID- 9238549
TI  - Differential aspects of sandplay with 10- and 11-year-old children.
AB  - OBJECTIVE: The aim of this study was to determine whether or not differences
      existed between control and clinic children at one age group in terms of how they
      undertook a sandplay picture task. Relatedly, it was seen as important to
      determine whether or not groups were indeed disparate in terms of amount of
      emotional stress or suffering. METHODOLOGY: An experimental comparison of the
      sandplay behavior and pictures of 10 and 11 year olds was conducted, with
      subjects equally distributed in two primary groups, clinic and control. Twenty
      six clinic children (13 males and 13 females) were included, who had experienced
      sexual, physical, and/or emotional abuse. Twenty-six control children (13 males
      and 13 females) were also included. All children came from the same metropolitan
      area. In order to validate the assumption that these two groups were distinct on
      the dimension of distress, the Achenbach Child Behavior Checklist was
      administered. An interrater counting technique was used to evaluate photographs
      of the pictures and score for content and theme. RESULTS: Results indicated that
      there were differences in the sandplay of clinic and control children in all
      three of the dependent variables; content, theme, and approach to the sandplay.
      Significant differences also existed between Achenbach groups. Most pronounced
      were the differences in approach to the sandplay, with clinic children, low
      competency and high problem children having difficulty staying within the
      boundary of the box, having more regressed play, and presenting more disorganized
      pictures. CONCLUSIONS: Sandplay pictures do differ between children who are
      experiencing emotional stress and those who are not. Sandplay may serve as a
      useful assessment tool in therapeutic work with children, as it is nonverbal in
      nature and generally popular with younger clients. More studies are needed which
      replicate this methodology, and which increase subject numbers.

PMID- 9238550
TI  - A meta-analytic investigation of group treatment outcomes for sexually abused
      children.
AB  - OBJECTIVE: A meta-analytic review of outcome studies of group treatment for
      sexually abused children and adolescents was conducted to establish a
      quantitative measure of group treatment effectiveness for this population.
      METHOD: The psychological literature was searched for studies which met the
      following criteria: The effectiveness of group treatment for sexually abused
      children or adolescents was investigated, results were based on empirical
      measures, and sufficient statistical information was reported to calculate effect
      sized. This search resulted in 15 studies. Overall effect sized were then
      calculated for each study and an overall mean effect size across studies was
      calculated. Additionally, effect sizes were compared to assess for effects of
      group characteristics, response perspectives, and type of outcome variables used.
      RESULTS: The overall mean effect size across studies was .79. Effect size
      comparisons based on response perspective and outcome variable groupings yielded
      no significant differences. While statistically insignificant, a trend of larger
      effect sizes for groups comprised exclusively of females was found. CONCLUSIONS:
      Results from the current meta-analysis support the conclusion that effective
      group treatments for sexually abused children and adolescents exist and that the
      current meta-analysis can function as a comparison group for future researchers
      studying treatment outcome for this population. Suggestions for research are
      discussed.

PMID- 9238551
TI  - The professional carers' group: supporting group work for young sexual abusers.
AB  - OBJECTIVE: A centralized treatment project, for young people who have sexually
      abused others, describes how group-based work with potentially isolated local
      professionals may help a treatment program to maintain a systemic perspective.
      METHOD: The paper reviews relevant literature and outlines the context, format
      and goals of a Professional Carers' Group. RESULTS: Recurring themes, observed
      during the 30-week treatment programs, are subjected to clinical analysis. Two
      key areas are discussed: (1) cognitive-emotional processing of common reactions
      to work with sexual abuse; and (2) inter-professional communication to balance
      the requirements of child protection and therapy. CONCLUSION: Concurrent work
      with local professional networks may promote the clinical effectiveness of a
      treatment program for young perpetrators of sexual abuse. A Professional Carers'
      Group is one relatively low-cost approach which may help to integrate the work of
      a central treatment facility with that of distant, community-based, agencies.

PMID- 9238552
TI  - The cumulative effect of neglect and failure to thrive on cognitive functioning.
AB  - OBJECTIVE: A cumulative risk model was used to examine the relationship among
      neglect, failure to thrive (FTT), and cognitive functioning in low income
      children. METHOD: A sample of 177 children 3 to 30 months old was recruited from
      a pediatric clinic serving low-income, primarily African American families. Four
      groups were formed based on neglect and FTT status: Neglect and FTT, Neglect
      Only, FTT Only, and No Neglect or FTT. FTT was defined as weight-for-age below
      the 5th percentile on growth charts. To avoid the biases associated with Child
      Protective Service reports as definitions of neglect, the HOME scale (Caldwell &
      Bradley, 1984) was used to define neglect. RESULTS: The cognitive performance of
      the group with neglect and FTT was significantly below that of the children in
      the Neglect Only, FTT Only, and No Neglect or FTT groups. CONCLUSIONS: These
      findings support a model in which the accumulation of risk factors is detrimental
      to cognitive functioning. The results also underscore the need for thorough
      evaluation when one risk factor has been identified. Growth failure may come to
      the attention of medical personnel, but neglect may not be detected. However, a
      child experiencing both neglect and FTT may be at risk for significant deficits
      in cognitive functioning.

PMID- 9238553
TI  - Evaluation in clinical practice: problems, precedents and principles.
AB  - 'Audit' is now in widespread use in our National Health Service, but there is
      little documentation of improvement resulting from audit. If it is to be used to
      identify mistakes in clinical practice, we must be prepared to admit them, or to
      have our work evaluated by others; such openness is uncommon. Understandably,
      doctors are concerned about possible litigation, undermining of their authority,
      and/or interference with their methods of practice. Furthermore, few are willing
      to comment adversely on the work of others. There is confusion about the best
      method(s) of audit. Outcome and process audit serve different purposes. Outcome
      audit measures the effect of care on patients' health, but in individual cases a
      poor outcome may result after impeccable medical care and a good outcome after
      poor care. Outcome audit requires a large patient group, is costly, and is of
      value for a limited number of conditions. Appropriate standards are needed to
      judge the results; it may be fallacious to compare outcomes in different
      settings, and with different patient groups. Furthermore, outcome audit is of
      little value for auditing the care given by individual doctors, and this limits
      its value in clinical education. Process audit deals with the appropriateness of
      clinical actions, on the assumption that they affect outcome. It can detect poor
      performance when outcome audit would be unlikely to identify poor outcome. For
      common or well-defined problems, process audit can make use of clear criteria,
      for example agreed protocols, and this may have immediate benefit for individual
      patients. When there is no agreed protocol the overall quality of care can still
      be audited against relatively explicit criteria, if there is agreement on the
      relevant 'principles of clinical practice', i.e. the rules which should guide the
      clinical management of individual patients. Clearly these should cover the
      collection, recording and analysis of patient data; planning for diagnosis,
      monitoring, treatment and patient education, and steps to be taken when there is
      uncertainty about the best course of action. Performance in these areas can be
      assessed by reviewing the patients' notes, but most clinical records are
      inadequate for this purpose. Process audit can be applied to all clinical
      problems, and is the method of choice for assessing the actions of individuals.
      Its educational value is self-evident. It allows the identification of
      deficiencies, and the provision of feedback to correct them. Furthermore, it
      provides for a continuum of audit through the undergraduate and postgraduate
      years of a doctor's training.

PMID- 9238554
TI  - Acquisition and use of clinical data for audit and research.
AB  - Acquisition of adequate patient data for clinical management is hard enough, but
      higher quality patient data are needed for clinical audit and research. This
      article discusses some of the problems of using routine clinical data for audit
      and research, aspects of data quality, sources of audit or research data and
      their problems, methods for improving data quality, the benefits and problems of
      computer-based systems and current trends in the capture and processing of
      clinical data.

PMID- 9238555
TI  - Meta-analysis of best-evidence synthesis?
AB  - This article examines the usefulness of meta-analysis, and articulates many of
      the criticisms that have been made of its workings. An attempt is made to outline
      the precautions that have to be taken before a scientifically useful and
      meaningful meta-analysis can be carried out. The problems encountered include
      heterogeneity of samples, conditions, interventions and end-points; narrow focus;
      curvilinearity of regression; lack of independence of determinants; synergistic
      interactions; contradictory experimental results. It is suggested that best
      evidence synthesis, or theory-directed analysis, might be a safer option.

PMID- 9238556
TI  - Developing clinically valid practice guidelines.
AB  - Valid guidelines, when appropriately disseminated and implemented, can lead to
      changes in clinical practice and improvements in patient outcome. Guidelines are
      more likely to be valid if they are developed using systematic reviews, national
      or regional guideline development groups (including representatives of key
      disciplines) and explicit links between recommendations and scientific evidence.
      This paper discusses the practical implications of adopting this approach for
      guideline development and the role of peer review guidelines as another element
      of the process to ensure validity. Considerable resources are required to develop
      evidence-linked guidelines, but this investment can be recouped by relatively
      small changes in the process or outcome of care. Good leadership and technical
      support are required for the successful development of clinically valid
      guidelines, which is dependent upon the small-group processes of guideline
      development panels and the translation of evidence into recommendations. Future
      guideline developers need to gain expertise in these areas. Research priorities
      are identified.

PMID- 9238557
TI  - Clinical guidelines and the law: advice, guidance or regulation?
AB  - Proliferation of clinical guidelines has given rise to a number of concerns about
      the status of clinical advisory statements. Are guidelines advisory or mandatory?
      What regulatory functions do guidelines serve; do they allow clinical discretion
      a large enough role? Relationships between legislation and guidelines, and the
      way courts go about determining the legal status of guidelines, are explained.
      The following questions in the context of the law of negligence are addressed. Do
      doctors who deviate from guidelines place themselves at increased risk of being
      found liable in negligence if patients suffer injury as a result? Could
      compliance with guidelines protect health care workers from liability in such
      circumstances? What legal responsibility do the developers and issuers of
      guidelines have if their guidance is found to be faulty? Common law cases
      featuring clinical guidelines or protocols have been identified from the database
      Lexis, which searches the full text of the transcripts and reports of court cases
      in UK, Commonwealth and United States jurisdictions. Secondary literature,
      identified from the bibliography of clinical guidelines maintained by the
      Department of Health Services Research at the University of Aberdeen (assembled
      from DHSS-DATA, Embase, Grateful Med, Medline and SIGLE) has also been consulted.
      The legal status of a guideline turns on whether its development and application
      have statutory backing, and whether the guideline embodies clinical practices
      accepted as proper by a responsible body of doctors. The mandatory effects of
      guidelines can be gauged, to some extent, by the sanctions that apply in the
      event of non-compliance. US courts have ruled that guideline developers can be
      held liable for faulty guidelines, and that doctors cannot pass off their
      liability by claiming that adherence to guidelines has corrupted clinical
      judgement. Protocols and guidelines provide the courts with examples of clinical
      standards across a wide range of medical practice. As guidelines proliferate, so
      they will increasingly be used in court. However, adherence to guidelines has not
      automatically been equated with reasonable practice, and the courts seem unlikely
      to follow the standards enunciated in clinical guidelines without critically
      evaluating their authority, flexibility and scope of application.

PMID- 9238558
TI  - Health services research: an expanding field of inquiry.

PMID- 9238559
TI  - The role of health economics in clinical evaluation.

PMID- 9238560
TI  - Is clinical practice improved by risk management?

PMID- 9238561
TI  - Brief encounter: a dialogue between a philosopher and an NHS manager on the
      subject of 'quality'.

PMID- 9238562
TI  - Purchasing quality in clinical practice: what on Earth do we mean?

PMID- 9238563
TI  - Getting there from here: evidentiary quandaries of the US outcomes movement.
AB  - The US outcomes movement assumes, and sometimes argues, the primacy for medical
      practice of probabilistic knowledge derived from methodologically rigorous
      statistical studies. 'Evidence-based medicine,' then, is considered a course of
      clinical medicine prescribed by such research. Implementation of evidence-based
      medicine as recently been uneven in the US, manifesting not only the expected
      'obstacles to implementation' but several theoretical weakness of the applied
      science model of medical care. Outcomes researchers claim to provide certainty -
      certainty of what is probable, as it turns out - in a world of clinical
      uncertainty. This paper argues that outcomes research actually exacerbates the
      inferential uncertainty of practising physicians who would use knowledge for
      practice. Two quandaries are discussed: whether to privilege rigorous or relevant
      research, and whether to privilege universal or local knowledge. In each case,
      the logic of 'evidence-based medicine' is insufficient to resolve the quandary
      and would seem to support conflicting resolutions. Recent developments in US
      health policy are cited as manifestations of these quandaries. Finally, the
      reader is asked not to disregard the political implications of the outcomes
      movement.

PMID- 9238565
TI  - Detecting poor design, erroneous analysis and misinterpretation of studies.
AB  - To detect bad research in published articles, it is necessary to know what to
      look for. Some examples of the types of poor study design, inappropriate analyses
      and pitfalls of interpretation which can occur are presented.

PMID- 9238566
TI  - Systematic reviews of randomized controlled trials: the need for complete data.
AB  - If the relative effectiveness of different treatments that might be used in
      clinical practice is to be evaluated reliably, it is very important that the
      evaluation is carried out in an appropriate manner. This is especially true where
      the differences between treatments are expected to be moderate, and so easily
      obscured by the play of chance or systematic bias. Although such differences are
      often of considerable clinical importance, they can be difficult to assess and
      require a large amount of randomized evidence. This evidence can be obtained
      through prospective randomized controlled trials, meta-analysis of results from
      past randomized trials, or ideally a combination of the two, with prospective
      trials contributing to future meta-analyses. Whichever technique is adopted, all
      possible biases must be minimized through the collection of as much randomized
      evidence as possible. In meta-analyses, this is best achieved by ensuring that
      all relevant trials, and all randomized participants in these trials, are
      included in the analysis. The gold standard for this might be a meta-analysis of
      individual patient data, in which details for each participant in every trial are
      collected and analysed centrally. This approach requires considerable time and
      effort. However, it will add to the analyses that can be performed and will
      remove many of the problems associated with a reliance on published data alone
      and some of the problems that can arise from the use of aggregate data. This
      paper sets out some of the reasons for this and some of the techniques used for
      individual patient data-based meta-analysis.

PMID- 9238564
TI  - Case mix adjustment in comparative audit.
AB  - There is increasing pressure to measure and publicize the quality of health care,
      with, for example, hospital 'league tables' appearing regularly in the lay press.
      Equally, there is increasing recognition that such simplistic presentations of
      data can be seriously misleading, as differences in case mix mean that they do
      not compare like with like. We discuss what is required of a statistical model if
      it si to be used to make comparisons of clinical performance which are adjusted
      for case mix. Outcome measures must be well defined and relevant, and the risk
      factors used in the model must reflect the patients' potential prognosis rather
      than aspects of his or her clinical care. In addition, the calibration of the
      statistical model is crucial. We review a number of established clinical scoring
      systems and demonstrate that they fail to meet all of the required criteria. Of
      particular concern is the fact that these scoring systems are susceptible to
      biases which could actually mask differences in performance. We highlight areas
      where further research is required, with the aim of stimulating progress in this
      field.

PMID- 9238567
TI  - The case for failed meta-analyses.

PMID- 9238568
TI  - Effective practice.

PMID- 9238569
TI  - Consumer audit. A speech to the second National Medical and Dental Audit
      Conference, 4 April 1995.

PMID- 9238570
TI  - Evidence-based medicine: reference? Dogma? Neologism? New orthodoxy?

PMID- 9238571
TI  - Rationing and evidence-based medicine.

PMID- 9238572
TI  - The protagonists of 'evidence-based medicine': arrogant, seductive and
      controversial.

PMID- 9238573
TI  - Central dimensions of clinical practice evaluation: efficiency, appropriateness
      and effectiveness--I.
AB  - Successful audit of clinical practice focuses upon the systematic investigation
      of key aspects of the everyday work of busy clinicians. We contend that the
      nature and quality of local clinical practice can be characterized by critical
      examinations of the effectiveness and appropriateness of practice and the
      efficiency with which effective, appropriate clinical care is delivered to
      patients. When such a baseline has been established, it becomes possible to
      compare and contrast characterized local practice with so-called 'evidence-based'
      practice and agree changes aimed at narrowing the discrepancy between the two.
      The nature of such changes can be described and their implementation into
      practice studied, with subsequent quantitative measurement and qualitative
      description of the resulting benefits to patients. A proper understanding of the
      concepts of efficiency, appropriateness and effectiveness in clinical care is
      clearly fundamental to the successful design and applications of methodologies
      aimed at securing measurable improvements in the quality of patient care. In this
      first of two articles we examine the concepts of efficiency and appropriateness
      in clinical practice, with particular emphasis on cost-effectiveness and
      utilization review. The clinical effectiveness of health care intervention is
      treated in detail within the second paper, to be published within Volume 2 Number
      2 of the Journal of Evaluation in Clinical Practice (Miles et al. 1996f).

PMID- 9238574
TI  - Clinical audit in the National Health Service: fact or fiction?
AB  - It is increasingly recognized that the repeated rhetorical emphasis from 1989 to
      date on achieving measurable benefits to patients from audit, in the face of
      inattention to the development of methodologies with which to realize such
      benefits in operational practice, has represented a serious deficiency in
      strategic planning and direction and a consequent failure to establish functional
      clinical audit within the NHS. A grand revision of strategy is therefore
      necessary, and this should begin with the development of a research-based method
      of audit, the training of clinicians and audit support staff in its use and a
      subsequent trial of its effectiveness prior to its implementation within the NHS.
      Only then will measurable improvements become possible, value for money be
      assured and clinicians' attitudes to audit change.

PMID- 9238575
TI  - The Total Health Care Audit System: a systematic methodology for clinical
      practice evaluation and development in NHS provider organizations.
AB  - Writing in Medical Education in 1982, Fowkes (1982) noted the lack of general
      agreement within the medical profession on methods of audit, a deficiency
      previously articulated by Shaw (1980) and later emphasized by McIntyre (1985).
      More recently, a study by Black & Thompson (1993) of consultant and junior
      medical staff in four London district general hospitals revealed that 'many
      doctors did not understand how to undertake audit', and major research by both
      Hopkins (1993, 1994) and Buttery et al. (1994) described a multiplicity of
      methodological deficiencies in the general approaches to audit adopted by
      clinicians since the promulgation of the White Paper definition in 1989.
      Soundness of methodological approach is fundamental to securing the success of
      clinical audit within Provider organizations and is thus central to the
      generation of measurable improvements in the quality of clinical care being
      delivered to patients. It is therefore disturbing that methodological
      deficiencies may still be observed in general approaches to audit (Buttery et al.
      1994), with no author yet recommending a formal system for critical inquiry into
      clinical practice. It was the recognition of the unsatisfactory nature of this
      situation which led us to develop a system aimed at assessing, in a critical
      fashion, the quality of the totality of care dispensed within NHS provider
      organizations. The system is presented here for the first time.

PMID- 9238576
TI  - Integrated care pathways: effective tools for continuous evaluation of clinical
      practice.
AB  - The critical examination of clinical practice should be an integral part of
      patient care. It includes the development and implementation of guidelines,
      together with continuous evaluation of clinical process and outcomes to improve
      the quality of care provided. Clinical audit has not been successful in achieving
      this. The use of Integrated Care Pathways facilitates the introduction of
      guidelines and the continuous evaluation of clinical practice. Improvements are
      achieved by frequently revising the pathways to reflect current, local best
      practice. Integrated Care Pathways define the expected course of events in the
      care of a patient with a particular condition, within a set time-scale. A pathway
      is divided into time intervals during which specific goals and expected progress
      are defined, together with appropriate investigations and treatment. A pathway
      reflects the activities of a multidisciplinary team and can incorporate
      established guidelines and evidence-based medicine. It is usually unique to the
      institution in which it was developed. The pathway forms part of the clinical
      record of every patient. All variations from the pathway are documented, and the
      reasons for the variations analysed. Solutions are developed to address the
      causes of potentially avoidable variation, and the pathway is revised to
      incorporate these improvements. Integrated Care Pathways provide a powerful audit
      tool, as all aspects of the process and outcome of clinical practice can be
      constantly monitored. Variations from set standards are minimized, and
      improvements are rapidly incorporated into routine practice and subsequently re
      evaluated.

PMID- 9238577
TI  - Monitoring outcomes in routine practice: defining appropriate measurement
      criteria.
AB  - With the development of an internal market for health care, 'purchasing for
      outcomes' has become an important if somewhat rhetorical catchphrase. While there
      is emerging understanding about how it can be pursued, doubts are being expressed
      over an outcomes rather that a process emphasis. This debate has been confused by
      a failure to differentiate the role and importance of monitoring outcomes at an
      individual patient care level from those at an aggregate population/purchaser
      level. The clinical need to collect outcomes data on individual patient care
      within routine care settings places additional requirements on measurement
      development and selection. Traditional measurement criteria, stressing
      reliability, validity and responsiveness to change, must be supplemented by
      criteria of feasibility of use, clinical utility and acceptability. One option is
      to select domains or items of interest from longer instruments initially designed
      for research, carefully selected in relation to the purposes of measurement.
      Further measurement criteria must be addressed which stress the relevance of the
      proposed instrument to the condition and to the participants in the clinical
      interaction: in particular, patient-centredness and sensitivity to the setting.
      Monitoring the outcomes of individual patient care within routine clinical
      practice poses considerable challenges to researchers who are developing
      instruments and to clinicians who collect and use the data. A shift in emphasis
      is required towards more context-specific tests, addressing relevance to lay
      perceptions, to clinical use and to the condition and setting under review. The
      content validity, the responsiveness to patient-relevant and clinically relevant
      change and, of course, reliability must have greater primacy. In this way,
      outcome data which measure the quality of clinical practice and which provide
      appropriate criteria for research into effectiveness can be generated.

PMID- 9238578
TI  - The role of research in setting priorities for health care.
AB  - Research of all types plays a fundamental role in setting health care priorities,
      in part by informing the development of robust clinical practice guidelines.
      Today's investments in research may make tomorrow's choices about who gets what
      kinds of care easier, not more difficult. The converse also holds: today's
      investments in providing care, if made at the significant expense of research,
      will not make tomorrow's choices about care any easier. In making choices and
      balancing priorities, the centrality of health services research must be
      understood. The information necessary to make the hard choices about priorities
      in health care today may be generated as much, if not more, from investments in
      this field of inquiry as from equivalent investments in other arenas of
      scientific endeavour, because of the growing need for information about the
      effectiveness of health care and in making better use of health resources.

PMID- 9238579
TI  - The language of quality.
AB  - Management theorists have developed a language which, they claim, can be used to
      evaluate many diverse practices, including practices in health care. This
      language embodies conceptualizations of practice and an approach to evaluation
      which treat the concept of quality as foundational and which have links with free
      market ideology. Despite an extensive literature which attempts to apply this
      language to various areas of life, its fundamental conceptual assumptions remain
      largely unexamined. Without adequate philosophical arguments in support of these
      assumptions, the value of this language and the validity of the approach to
      practice that it embodies are unproven. Its imposition in the absence of such
      arguments therefore represents a form of intellectual imperialism. To understand
      and develop adequate responses to this situation, it is necessary to look at the
      broad political picture which affects the nature of debates in specific areas of
      practice, such as the health service, and to question the dominant paradigm
      governing practical debate in contemporary society.

PMID- 9238580
TI  - User involvement in clinical audit: a review of developments and issues of good
      practice.
AB  - There have been considerable political and organizational moves to involve
      'consumers' (patients, carers, service users, potential users, local communities
      and the public at large) in the provision, planning and monitoring of health
      services. Such developments beg the question 'what constitutes good practice in
      user involvement?'. Taking user views into account relates not only to obtaining
      feedback on 'hotel' aspects of care (issues such as food and cleanliness) but
      also to the potential for patient input to clinical audit and the standards by
      which care itself is measured. Recent policy statements specifically advocate
      involving users in the process and product of clinical audit. In practice,
      'involvement' has meant anything from passing on information to full and active
      participation in partnership with professionals. This paper outlines some of the
      issues raised in the published literature on user involvement in clinical audit.
      Suggesting that real involvement refers to users as active participants, not
      passive recipients, the paper documents the increasing policy commitment to user
      involvement and considers issues that influence how the rhetoric is put into
      practice.

PMID- 9238581
TI  - Measuring the effects of casemix on outcomes.
AB  - Participation in the measurement of population health and health care outcomes
      has become an explicit professional duty for doctors, but comparisons are
      difficult to make because outcomes are conceptually complex and largely
      qualitative. Observational data, particularly from routine hospital statistics,
      are useful complements to experimental data provided that their variable quality
      is taken into account and adjustments are made to minimize bias and confounding
      and to allow for the effects of differences in casemix, which are problematic
      because of the nature of severity.

PMID- 9238582
TI  - Qualitative research in health care: I. The scope and validity of methods.
AB  - It is increasingly argued that qualitative approaches have an important role in
      health care research. A wide range of methods are used to collect qualitative
      data, including in-depth interviews, focus groups and observational methods such
      as participant observation. The reliability and validity of qualitative studies
      can be addressed by a variety of techniques. Although there is less consensus
      about appropriate methods of analysing qualitative data, such analyses tend to be
      grounded in the data, and involve iterative procedures and the development and
      refinement of typologies, analogies and other forms of concept to make sense of
      data.

PMID- 9238583
TI  - Central dimensions of clinical practice evaluation: efficiency, appropriateness
      and effectiveness--II.
AB  - That a treatment selected for a given condition works, or that it works better
      than alternative treatments, or that it was selected because it works as well as
      but is cheaper than alternative treatments, should be of pivotal concern to
      clinicians and is of central concern to patients and to health care managers.
      Attempts to address these concerns have resulted in what is now widely termed the
      'effectiveness movement'. The protagonists of the movement have been concerned to
      create a culture of evaluation and inquiry within which the formulation of
      evidence-based clinical guidelines and their introduction into routine practice
      have played a prominent part. The need to ensure cost effectiveness of clinical
      intervention has been at least as emphasized as the need to ensure the clinical
      effectiveness of health care interventions. Although cost-effectiveness analyses
      are now an indispensable feature of practice guideline formulation and treatment
      evaluation, few studies have examined any deterioration in patient outcome
      associated with successful cost containment. An adequate understanding of the
      concept of clinical effectiveness and the associated aims of the 'effectiveness
      movement' is central to an understanding of the future nature and extent of
      health service provision, not simply in the UK but also internationally. Having
      examined the concepts of efficiency and appropriateness previously (O'Neill,
      Miles & Polychronis 1996, Journal of Evaluation in Clinical Practice 2, 13-27) we
      move in this second of two articles to a detailed explanation of the concept of
      effectiveness, and to an examination of the derivation and use of clinical
      practice guideline, concluding with a consideration of the role of practice
      guidelines in ensuring the cost effectiveness of health care intervention. The
      reservation is expressed that a 'guidelines culture', when established, will be
      manipulated by health care commissioners for largely political purposes, creating
      a systematic bias in the purchasing process that will actively disadvantage a
      range of patient groups.

PMID- 9238584
TI  - Conceptual differences amongst the data collection instruments used in clinical
      audit.

PMID- 9238585
TI  - The future of clinical research: from megatrials towards methodological rigour
      and representative sampling.
AB  - A powerful impetus behind the rise of the 'megatrial' (a large, simple, usually
      multi-centred randomized controlled trial analysed by 'intention to treat') has
      been the desire for ever-increasing precision in the measurement of therapeutic
      effectiveness. However, the demand for precision has been allowed to override
      other and more important methodological considerations. Megatrials have
      progressively abandoned the pursuit of scientifically rigorous experimentation,
      valid measurement and optimal epidemiological sampling in favour of recruiting
      and processing large number of subjects. This is a mistaken strategy which leads
      inevitably to error, because investigators are seeking a primarily statistical,
      rather than clinically or scientifically relevant, notion of exactness. We are
      now in a position to describe a clinical research strategy which offers many
      advantages over a megatrial-led approach. Research should be planned with an
      awareness that the validity and applicability of estimated is more important that
      their numerical precision, and that this requires both and unselected denominator
      population database of all incident cases, and maximally controlled randomized
      trials and other studies. The Population-Adjusted Clinical Epidemiology (PACE)
      strategy is suggested as exemplifying the twin principles of clinically useful
      research: rigorous science and representative epidemiology.

PMID- 9238586
TI  - Qualitative research in health care: II. A structured review and evaluation of
      studies.
AB  - A hand search of the original papers in seven medical journals over 5 years was
      conducted in order to identify those reporting qualitative research. A total of
      210 papers were initially identified, of which 70 used qualitative methods of
      both data collection and analysis. These papers were evaluated by the researchers
      using a checklist which specified the criteria of good practice. Overall, 2% of
      the original papers published in the journals reported qualitative studies.
      Papers were more frequently positively assessed in terms of having clear aims,
      reporting research for which a qualitative approach was appropriate and
      describing their methods of data collection. Papers were less frequently
      positively assessed in relation to issued of data analysis such as validity,
      reliability and providing representative supporting evidence. It is concluded
      that the full potential of qualitative research has yet to be realized in the
      field of health care.

PMID- 9238587
TI  - Some methodological issues in the development of quality of life measures for the
      evaluation of medical interventions.
AB  - This paper discusses a series of important methodological issues in developing
      targeted health-related quality of life measures in studies of the effects of
      medical interventions. Such measures cannot be developed unless the evaluator
      understands the life domains that medical interventions affect. Qualitative
      discovery methods are needed to obtain this understanding. Once domains are
      targeted for measurement, careful and systematic laboratory pilot work should be
      used to select initial scale items. Psychometric evaluation of response patterns
      in subsequent field tests is needed to assess the measures. Less concern should
      be directed to internal consistency reliability of scales in the psychometric
      evaluation and more to the ability of short scales to reproduce total scale
      variance and to provide precise measurement within the range of the outcome where
      effects are expected. The paper closes with a discussion of modern methods of
      item response scaling that can be used to address these issues.

PMID- 9238588
TI  - The involvement of pharmacists in professional and clinical audit in the UK: a
      review and assessment of their potential role.
AB  - This review addresses the uptake and implementation of the principles of audit by
      community, hospital and health authority pharmacists. The pressures to audit
      professional services are discussed, as are the barriers to cooperation among
      pharmacists and between pharmacists and prescribers in primary care. The
      development of standards of professional practice is then described taking into
      account the particular difficulty in developing standards for health care workers
      who are geographically separated from other members of the primary care team and
      are in commercial competition with each other. The review identifies audit of
      professional services in both community and hospital pharmacy and of clinical
      services in the latter. The role of pharmacists employed by health authorities to
      advise them and general practitioners on the optimum use of the drug budget is
      described and their potential role for involvement in audit is discussed. The
      particular advantages that pharmacists in hospital and health authorities have in
      developing the specific aspect of clinical audit related to medicines usage (drug
      utilization review) is then described. The potential for pharmacists to
      contribute to clinical and management audit is discussed.

PMID- 9238589
TI  - Audit: the emperor's new clothes.

PMID- 9238590
TI  - Decision making in health care: introduction.

PMID- 9238591
TI  - Overview and critique of judgement and decision making in health care: social and
      procedural dimensions.
AB  - This paper presents an outline of the scope for the application of decision
      theory to health care. Firstly, the main approaches to and assumptions of
      decision theory are discussed. Secondly, health care decision making is reviewed.
      It is noted that decision theory can be applied to either the health care
      professional or to the lay person. Applications of decision theory to clinical
      practice, to the management of care and to resourcing are considered. Thirdly,
      some areas which would repay further research are identified. These include
      social processes in individual and group decision making, the temporal
      distribution of outcomes and the development of techniques capable of dealing
      with the complex and dynamic features of decisions. On the basis of the
      foregoing, some conclusions are drawn.

PMID- 9238592
TI  - Judgements and processes in care decisions in acute medical and surgical wards.
AB  - The decisions which health care professionals make are the basis of treatment and
      care given. In order to evaluate effective care it seems logical to suggests that
      an awareness of the decisions which health care professionals make and how they
      make them is needed. This study examines the processes nurses use when making
      decisions about the health care needs of acutely ill patients. In stage one, 104
      qualified nurses were interviewed to identify how they decide health care needs.
      In stage two, a 'think aloud' technique was used with patient simulations to
      obtain verbal protocols from a further 55 qualified nurses to identify the
      information strategies they used when making these decisions. The results suggest
      that nurses base their health care decisions mainly on their assessment of
      qualitative patient states or conditions. Initial indications are that the
      processes used differ from those characterized in the diagnostic reasoning model,
      with the context in which decisions are made being an important influence
      together with nurses' experience. It is suggested that, in order to develop
      effective predictive models and clinical guidelines which aid decision making,
      more research into the nature of health care professionals' decision making is
      carried out.

PMID- 9238593
TI  - Comparison between the Health Belief Model and Subjective Expected Utility
      Theory: predicting incontinence prevention behaviour in post-partum women.
AB  - A small-scale study was undertaken to test the relative predictive power of the
      Health Belief Model and Subjective Expected Utility Theory for the uptake of a
      behaviour (pelvic floor exercises) to reduce post-partum urinary incontinence in
      primigravida females. A structured questionnaire was used to gather data relevant
      to both models from a sample antenatal and postnatal primigravida women.
      Questions examined the perceived probability of becoming incontinent, the
      perceived (dis)utility of incontinence, the perceived probability of pelvic floor
      exercises preventing future urinary incontinence, the costs and benefits of
      performing pelvic floor exercises and sources of information and knowledge about
      incontinence. Multiple regression analysis focused on whether or not respondents
      intended to perform pelvic floor exercises and the factors influencing their
      decisions. Aggregated data were analysed to compare the Health Belief Model and
      Subjective Expected Utility Theory directly.

PMID- 9238594
TI  - Decision making in HIV testing among a group with low HIV risk.
AB  - Relatively little is known about how individuals (apart from gay and bisexual
      men) decide to have an HIV test and how, once they have presented for testing,
      they make decisions about proceeding through the testing trajectory. This paper
      reports on a qualitative study in which 55 mainly heterosexual respondents with
      low HIV risk were interviewed about their experiences of decision making around
      HIV testing. Reasons for deciding to be tested centred on a desire for
      reassurance and the circumstances of the respondents' current relationship. The
      most common relationship reason focused on a desire to confirm HIV status before
      beginning sexual relations or engaging in unprotected sex with a partner.
      Although some respondents recognized that other individuals had influenced their
      decision to be tested, few said that pre-test counselling had been influential in
      this respect. Instead, it was said to have promoted feelings of 'ownership' of a
      decision which had already been taken prior to counselling. The potential effects
      of HIV testing on HIV risk behaviour were also examined and a non-significant
      increase in unprotected sex was reported between the month before the test and
      the month after. The implications of these findings for the provision of HIV
      testing services are explored.

PMID- 9238595
TI  - Decision making in health care: commentary.

PMID- 9238596
TI  - How to tame ostriches.

PMID- 9238597
TI  - Assessing quality of care: what are the implications of the potential lack of
      sensitivity of outcome measures to differences in quality?
AB  - Measuring outcome can be an insensitive way to detect differences in the quality
      of health care. This paper captures the implications of this poor sensitivity for
      the interpretation of studies of outcome that compare provider performance, and
      considers in what circumstances monitoring outcome might be useful. When
      interpreting studies, it is important to consider the size of the effect that a
      difference in the quality of care might be expected to have on outcome and
      whether it is likely that important differences in quality might not have been
      detected. It is argued that outcome measures may be of value when how you do
      something is as important as what you do, when process measures are invalid or
      impractical, and when the overall effectiveness of an intervention is critically
      dependent upon its complication rate.

PMID- 9238598
TI  - Evidence-based practice in primary care: past, present and future.
AB  - As in other health care specialities, evidence-based practice is beginning to
      have an impact on the philosophy and workings of primary care. Some practising
      clinicians, however, may wish to question its relevance to their everyday work,
      and whether general practitioners and other members of the primary health care
      team can realistically adopt a new approach to clinical decision making, at a
      time of such high workload and competing priorities. Major changes have taken
      place during the last 20 years as a result of the National Health Service (NHS)
      reforms, the development of general practice and primary care research, and other
      health service innovations such as the introduction of new technologies, which
      have had an important impact on primary care. Issues such as the availability and
      use of different research methods, the role of experts, and the development of
      guidelines, audit and evaluation of care, are becoming subject to renewed
      scrutiny. Within this context, this article explores the potential of an evidence
      based approach in the primary care setting, and discusses possible strategies for
      change to assist the dissemination of research into practice and the
      implementation of evidence-based health care.

PMID- 9238599
TI  - Accuracy and reliability of assessment of severity of illness before and after an
      educational intervention.
AB  - Severity-of-illness measurement is considered to be an important factor in the
      risk adjustment of medical outcomes. However, for those measures that involve a
      high level of clinical judgment, strategies have to be developed to maximize the
      consistency of rating severity that can be implemented, especially when rating is
      based upon medical record review. A group of 25 clinicians were sent the same set
      of 14 patient records, and requested to use the Duke University Severity of
      Illness (DUSOI) checklist to rate the severity of patients' illness. Written
      instructions for the use of this instrument were provided. A short educational
      intervention was than made by the research team, and the clinicians were sent the
      same set of records to be rated again. Any improvement in the accuracy and
      reliability of severity assessment over the two ratings was then studied. The
      educational intervention resulted in identification of fewer irrelevant health
      problems. However, it had little impact upon the reliability of severity scoring
      itself, as measured by the intraclass correlation coefficient. Measuring severity
      of illness is a conceptually complex procedure. However, given its role in
      outcome interpretation, it may be worth pursuing strategies aimed at maximizing
      consistency of clinician rating. There are a number of options, including
      improved written instructions and more intensive training, that could be
      implemented.

PMID- 9238600
TI  - The progress of lay involvement in the NHS Research and Development Programme.
AB  - The Central Research and Development Committee is seeking to involve lay
      perspectives in the NHS R&D Programme. This paper describes some recent examples
      of lay involvement in each step of the research process from setting the agenda
      to making use of research findings. Innovative approaches have involved lay
      people in identifying research need and in the subsequent commissioning process.
      Lay contributions have given particular emphasis to information and support,
      whether this is in maternity care, cancer care, HIV prevention, participation in
      clinical trials or systematically reviewing evidence of effectiveness.
      Difficulties in identifying appropriate lay people to involve in research, their
      different skills, their lack of resources and support and their need for time for
      thought and discussion with their peers have all posed problems. Suggestions for
      overcoming some of these obstacles are presented, including resources, training
      and support, and clarification of the role, nature and potential for lay
      involvement. Lastly this paper considers the urgent need to learn from the
      efforts made so far, possible approaches to evaluation and how this is being
      addressed by a newly convened advisory group to the Central R&D Committee.

PMID- 9238601
TI  - A method of estimating tooth life expectancy.
AB  - One of the most important outcome measures for dental services is the increase in
      tooth life expectancy which is brought about by the interventions provided. Thus,
      a convenient and accurate index of tooth survival is critical both to clinical
      decision making and to more general assessments of public dental health policies.
      This paper describes a simple method of approximating tooth life expectancy
      (TLE). The method is based on the assumption that tooth survival follows a simple
      declining exponential function. Assuming a constant mortality rate, TLE is the
      integral of the survival function, expressed as S(t) = e-mu t, where t is time
      and mu the constant mortality rate. Using 3-year tooth-specific mortality rates
      for 491 subjects aged 50 years or more, tooth-specific life expectancies for the
      population as a whole where found to range from 27 years for upper canines to 71
      years for lower incisors. Individuals with a mean periodontal attachment loss
      greater than 4 mm and people on low incomes had significantly lower tooth life
      expectancies than their periodontally fit and more wealthy counterparts. This
      technique can be used to obtain disease-specific or intervention-specific tooth
      life expectancies. Thus, gains in TLE for individuals with different oral, social
      and behavioural characteristics can be calculated. The declining exponential
      approximation of tooth life expectancy has the potential to become a powerful
      tool in the evaluation of dental services and treatments.

PMID- 9238602
TI  - Medical technology assessment and the role of economic evaluation in health care.
AB  - The growth in health care expenditure over the last few decades has necessitated
      the introduction of priority setting and decision making based on the results of
      critical evaluation. Medical technology assessment (MTA) is a valuable tool to
      assist policy makers in controlling existing and new medical technologies.
      Medical technology assessment and the role of economic evaluation as part of MTA
      are described, and various techniques of economic evaluation are discussed.

PMID- 9238603
TI  - Evidence into action: a conference on the challenges of putting evidence-based
      health care into practice. 23-24 May 1996, Birmingham, UK: a doctor's view.

PMID- 9238604
TI  - The limits of boardroom thinking at the bedside.

PMID- 9238605
TI  - The French clinical guidelines and medical references programme: development of
      48 guidelines for private practice over a period of 18 months.
AB  - The French medical profession and health insurance organizations have jointly
      committed themselves to a concept termed the 'medical regulation' of care. They
      decided to promote the quality of health care, judging that an approach based on
      quality was the best option for reducing the increase in health costs. The
      Clinical Guidelines and Medical References programme was entrusted to ANDEM
      (Agence Nationale pour le Developpement de L'Evaluation Medicale). Fifty working
      groups (669 experts) and 50 reading groups (1643 experts) met from June 1994 to
      November 1995 to produce guidelines. Learned societies were involved to propose
      experts. Hospital practitioners, doctors who specialized in the topic in question
      and those who did not had equal representation in the groups. The method
      consisted of a review of the literature to determine the level of scientific
      evidence. ANDEM's Scientific Council suggested modifications to the groups and
      agreed to disseminate 48 of the 50 texts. Careful observation of the operation of
      the groups identified factors that can positively influence the nature of the
      discussions and help avoid conflict: an abundance of high-quality literature, an
      understanding of clinical research methodology, the existence of guidelines from
      different institutions or different countries tending towards the same
      conclusions, good initial work carried out by the chairperson and the project
      manager, a limit to the number of questions asked of the group, the chairperson
      having good people skills and meeting-management skills, and an absence of
      professional and financial consequences for the participants. Good management of
      working groups is an additional factor in ensuring success. The regulatory
      medical references programme has led to changes of behaviour within the medical
      profession.

PMID- 9238606
TI  - Getting research into practice.

PMID- 9238607
TI  - Patient, physician and presentational influences on clinical decision making for
      breast cancer: results from a factorial experiment.
AB  - This study examines the influence of six patient characteristics (age, race,
      socioeconomic status, comorbidities, mobility and presentational style) and two
      physician characteristics (medical specialty and years of clinical experience) on
      physicians' clinical decision making behaviour in the evaluation treatment of an
      unknown and known breast cancer. Physicians' variability and certainty associated
      with diagnostic and treatment behaviour were also examined. Separate analyses
      explored the influence of these non-medical factors on physicians' cognitive
      processes. Using a fractional factorial design, 128 practising physicians were
      shown two videotaped scenarios and asked about possible diagnoses and medical
      recommendations. Results showed that physicians displayed considerable
      variability in response to several patient-based factors. Physician
      characteristics also emerged as important predictors of clinical behaviour, thus
      confirming the complexity of the medical decision-making process.

PMID- 9238608
TI  - The burden of waiting for hip and knee replacements in Ontario. Ontario Hip and
      Knee Replacement Project Team.
AB  - The objectives of this study were to assess the impact of major joint
      replacements in reducing pain and disability and to describe the burden of pain
      and disability that could be avoided by ordering the queues with respect to
      severity of disease. A secondary goal was to compare the uses of a general health
      status measure, the Short Form Health Survey (SF-36), and a disease-specific
      measure, the Western Ontario McMaster Osteoarthritis Index (WOMAC), for
      accomplishing the objectives. The results are based on interviews with 209
      patients before and after they had surgery. Only 15.9% of the patients had
      surgery within 3 months' waiting time, 19.2% waited 4-6 months, 30.7% waited 7-9
      months, and the remaining 34.1% waited a year or more. The waiting times were
      unrelated to the severity of pain or disability reported in the initial
      interview. Following surgery, there were large reductions in the WOMAC scores for
      pain, stiffness and difficulty in functioning. The SF-36 showed substantial
      improvements in relief from pain and in physical functioning, and reductions in
      role limitation due to physical problems, but not for scores related to mental
      health. The WOMAC scores were more responsive to the benefits of surgery than the
      SF-36 scores. Queuing systems keyed on burden of symptoms could reduce the burden
      of pain and disability suffered by patients awaiting surgery. The improvements
      from hip and knee replacements suggest that equitable access for these procedures
      should be a priority in Ontario.

PMID- 9238609
TI  - Is the patient's right to die evolving into a duty to die?: Medical decision
      making and ethical evaluations in health care.
AB  - When patient or family requests for continued life-sustaining treatments conflict
      with doctor recommendations, different conclusions as to what is beneficial for
      the patient may arise. Past practices usually accepted patient or family requests
      based on the principle of autonomy or that the doctor's primary responsibility is
      to the individual patient. Many patients die in intensive care units after
      doctors forego life-prolonging interventions. Health care changes and cost
      containment have led to a change in the classical ethical model of the patient
      doctor relationship such that concerns for societal requirements increasingly
      overrule those for individual patient needs. The ability to keep patients alive
      with little likelihood of recovery and the recognition of escalating health costs
      have led to calls for the needs of society and distributive justice to be taken
      into account. A tendency to justify a duty to die for these patients has arisen.
      Recent legal decisions in cases with conflicts between families and health care
      providers and institutions over foregoing life-sustaining therapies have decided
      for the families against doctors and hospitals, compelling institutions and their
      staff to act contrary to their ethical views. Value judgments of doctors are
      sometimes confused with medical indications for therapy. Doctors have defined
      therapies as futile or non-beneficial based on their own values and even
      withdrawn life-sustaining treatments without patient or family input. In some
      cases, the right to die is leading to the duty to die even against patient or
      surrogate wishes. Such observations indicate the need for rigorous analyses of
      medical decision making in this context and for ethical evaluations in health
      care in general.

PMID- 9238610
TI  - Using clinical audit to promote evidence-based medicine and clinical
      effectiveness--an overview of one health authority's experience.
AB  - Health care purchasers are facing increasing pressure to make the best use of
      their limited resources and to purchase only those services known to be
      clinically effective. This paper describes one health authority's experience of
      promoting clinical effectiveness through clinical audit and clinical guidelines.
      It highlights the central role of public health physicians in working closely
      with clinicians on the one hand and managers on the other, to promote evidence
      based medicine. The recent changes in the funding arrangements for audit have
      allowed purchases to have more say in what should be audited, and link audit and
      clinical effectiveness with contracts.

PMID- 9238611
TI  - Dialysis membrane biocompatibility and mortality and morbidity in acute renal
      failure.

PMID- 9238612
TI  - More on calcium channel blockers in nephrology.

PMID- 9238613
TI  - HMG-CoA reductase inhibitors in organ transplantation.
AB  - Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduces serum
      cholesterol in patients with high cholesterol blood levels including organ
      transplant recipients. HMG-CoA reductase inhibitor also inhibits a series of
      immune responses and thus have the potential of exerting immunosuppressive effect
      in patients with organ allografts. Experimentally, HMG-CoA reductase inhibitors
      reduces transplant arteriosclerosis. Whether this is linked to an
      immunosuppressive effect or not is unknown. There is little evidence that post
      transplant hyperlipidemia directly increases the risk of cardiovascular diseases.
      Lipid lowering with HMG-CoA reductase inhibitor is not indicated for all
      allograft recipients but should be used if other cardiovascular risk factors are
      present.

PMID- 9238614
TI  - Hyperhomocysteinaemia and end stage renal disease.
AB  - Vascular disease is a major cause of morbidity and mortality in end stage renal
      failure patients and cannot be explained entirely by the prevalence of
      traditional risk factors for atherosclerosis. A high plasma homocysteine
      concentration, which is a risk factor for vascular disease is found in patients
      with end stage renal disease. The exact cause for the hyperhomocysteinaemia seen
      in these patients is unknown, but is probably related to altered renal metabolism
      of homocysteine. High homocysteine concentrations may also be attributable to a
      deficiency of folate, vitamin B6 or vitamin B12 although, because of
      supplementation, these vitamins may be present in high concentrations in renal
      patients. The occurrence of hyperhomocysteinaemia despite high plasma vitamin
      concentration could be due to altered metabolism or inhibition of intracellular
      vitamin activity. A number of studies have now established hyperhomocystinaemia
      to be an independent risk factor for atherosclerosis in patients with end-stage
      renal disease. Plasma homocysteine concentrations can be reduced by
      administration of folic acid either alone or combined with vitamin B12 or vitamin
      B6. The effects of such reduction on vascular risk in renal failure patients
      needs further study.

PMID- 9238615
TI  - Recurrence of the original disease in pediatric renal transplantation.
AB  - Recurrent disease in the transplanted kidney is extremely common and yet accounts
      for less than 5% of graft loss in the adult population. In children, however,
      recurrence of the original disease has been responsible for over 6% of index
      graft failures and 12% of second graft failures in North America. The diseases
      that commonly lead to recurrence and consequent graft failure in children are
      primary glomerulo-nephritides such as focal segmental glomerulosclerosis (FSGS),
      systemic diseases of which hemolytic uremic syndrome (HUS) is best known for this
      complication and metabolic diseases of which primary hyperoxaluria (PH) is of
      importance. With the development of new therapeutic and surgical strategies, none
      of these conditions are now considered a contraindication for cadaveric (CAD) or
      living related donor (LRD) transplantation. Recurrent disease has also provided
      investigators a unique opportunity to study the pathogenesis of glomerular
      disease.

PMID- 9238616
TI  - Epidemiology of renal-cell carcinoma.
AB  - Renal-cell cancer is responsible for about 2% of all cancer deaths in developed
      countries and represents 80-85% of all tumors of the kidney. Its etiology is
      still largely undefined. Recently the results of a large international population
      based case-control study (International Renal-Cell Cancer Study), conducted
      between 1989 and 1991 in Australia, Denmark, Germany, Sweden and USA, including
      1732 cases and 2309 controls, showed an increased risk of renal-cell cancer in
      relation to tobacco smoking, elevated body mass index, a few medical conditions,
      the use of beta-blockers, a family history of the disease, high intake of dairy
      products and low intake of fruit and vegetables and, in women, multiparity. Most
      other studies agree about a causal role of cigarette smoking in the etiology of
      renal-cell cancer, although its association is less strong than for several other
      tobacco-related neoplasms, with a relative risk of about 2 for current smokers.
      Other established risk factors are elevated body mass index (mainly in women) and
      a family history of the disease. Occupational exposure to chemicals appears to
      have little significance, although associations with specific products, such as
      asbestos fibres, have been reported. Some relationship has been observed between
      renal-cell cancer and hypertension, use of anti-hypertensives and kidney
      diseases, although this issue remains open to discussion. Data are inconsistent
      on the role of nutrition, mainly for fats and proteins, while vegetable and fruit
      consumption seems to convey some protection on renal-cell cancer risk. The risk
      of renal-cell cancer was not materially elevated in relation to coffee, tea and
      alcohol intake and, in women, oral contraceptive use, hormone replacement
      therapy, and menstrual factors.

PMID- 9238617
TI  - Recombinant tissue plasminogen activator to declot dialysis fistulas.
AB  - BACKGROUND: Thrombosis is the most common complication of hemodialysis access.
      Few reports are available concerning the use of recombinant tissue plasminogen
      activator (rt-PA) to declot an arterio-venous (A-V) access. This report describes
      the use of rt-PA for this purpose in 17 A-V accesses. METHODS: The rt-PV was
      infused manually using a small catheter directly into the A-V access in 10-mg
      doses at 1-2 hour intervals, to a maximum dose of 40 mg. The procedure was
      followed by angiography, through the same catheter. RESULTS: One fistula could
      not be cannulated, and in three the lysis of the clot failed. The other 13 cases
      (3 fistulas, and 10 grafts 81%) had successful lysis with return of bruit and
      thrill. Most patients had dialysis the next day using the declotted A-V access.
      Angiogram detected stenosis in six patients and surgical revision was done 1-8
      days after the treatment. In the other seven patients no organic lesions were
      found, and six of them have a functioning A-V access 50-395 days after the lysis.
      Only 10-20 mg of rt-Pa was needed in 60% of the cases. No major complication
      occurred; minor local bleeding was noted in five patients (5/16, 31%).
      CONCLUSION: rt-PA can be considered safe, effective, and fast for declotting
      thrombosed arteriovenous fistulas.

PMID- 9238619
TI  - Erythropoietin treatment in renal anemia. How high should the target hematocrit
      be?

PMID- 9238618
TI  - Long-term effect of low molecular weight heparin on serum lipids in
      hypertriglyceridemic chronic hemodialysis patients.
AB  - Although low-molecular-weight heparin (LMWH) has been reported to lower serum
      triglycerides and raise HDL in patients previously receiving classic heparin for
      hemodialysis by sparing lipoprotein lipase activation, this is not universally
      accepted. To evaluate this effect we studied 14 hypertriglyceridemic patients on
      hemodialysis for a median of 61 months (range 6-168 months); six were males and
      eight females, with a median age of 54 years (range 30-78). Eight patients were
      on bicarbonate and six on acetate HD. Eight were receiving EPO. All had been
      given conventional heparin, 102 +/- 5.8 IU/kg, at least for the last six months
      (control period) before switching to LMWH. Mean LMWH dose was 77 +/- 3.1 IU/kg.
      Fasting levels of total cholesterol (TC), triglycerides (TG) and HDL were
      measured monthly during the control period and every trimester for the next 36
      months. Serum lipoproteins were measured at months 0 and 36 of the trial. TC, Lp
      alpha and beta showed no significant change. Serum TG and Lp pre-beta dropped
      significantly, to almost normal levels. EPO treatment, serum iPTH levels or
      dialysate buffer did not seem to influence this effect. HDL rose significantly
      higher in women than in men. It is concluded that LMWH substantially lowered the
      abnormally high serum TG and Lp pre-beta to almost normal and raised serum HDL in
      chronic hemodialysis patients.

PMID- 9238620
TI  - Endothelin and nitric oxide in hepatorenal syndrome: a balance reset.
AB  - The newly described endothelium-dependent vasoactive substances, nitric oxide and
      endothelins, have been the subject of intense investigative interest and have
      been demonstrated to promote a wide array of autocrine and paracrine functions.
      Recent data highlight their emerging role as potential important mediators of
      renal failure in general, thus suggesting that they might also contribute to
      renal dysfunction in the setting of advanced hepatic disease. Most but not all
      investigators, have demonstrated that circulating ET-1 levels are elevated in
      patients with advanced liver disease, and some reports have suggested that the
      magnitude of the elevation correlates with the degree of renal dysfunction.
      Concomitantly, several investigators have demonstrated NO overproduction as
      assessed by elevated levels of NO2- and NO3- in patients with advanced liver
      disease. It has been suggested that serum nitrite/nitrate levels are highest in
      patients with functional renal failure (i.e., HRS) and that these levels
      correlate with the magnitude of endotoxemia. Although large voids in our
      knowledge remain, the available evidence suggest that a reset balance between
      vasoconstrictor and vasodilatory stimuli may contribute to the renal hemodynamic
      abnormalities that characterize the renal functional abnormalities of liver
      disease.

PMID- 9238621
TI  - Incidence and consequences of post-transplantation lymphoproliferative disorders.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a recognized severe
      complication arising in allograft recipients treated with immunosuppressive
      drugs. Although not common, PTLD is one of the most frequent tumours among graft
      recipients, comprising 15-25% of neoplasms, compared with 5% in the general
      population. The introduction of cyclosporin A (CyA) in the early 1980's and the
      very potent new immunosuppressants such as anti-CD3 monoclonal OKT3 and FK506
      have been associated with a significant rise in the incidence of PTLD and with
      their earlier presentation. The incidence of this malignancy varies with the
      organ transplanted (1-2% of renal transplant recipients) and with the nature and
      severity of the accompanying immunosuppressive regimen. While the precise
      etiology of PTLD is still unclear, significant advances have been made recently
      in the understanding of its pathogenesis. Most PTLD tumour cells present an
      activated B-cell phenotype and an unrestricted pattern of latent EBV gene
      products. It is generally accepted that Epstein-Barr virus (EBV) infection or
      reactivation and intensive anti-T lymphocyte regimens play a major role in the
      genesis of PTLD. They include a spectrum of EBV-related disorders ranging from
      lymphoid hyperplasia to frank malignant non-Hodgkin's lymphoma. Although
      different therapeutic attempts have been proposed, optimal treatment remains
      elusive. The mortality rate for monoclonal lymphomas was reported to be as high
      as 80%. Infusion of anti-B monoclonal antibodies seems to be a promising
      modality. Different preventive approaches have been proposed, including EBV sero
      negative donor/recipient matching and careful monitoring of EBV infection.
      Cautious use of anti-rejection treatment in combination with prophylactic
      antiviral therapy is recommended.

PMID- 9238622
TI  - Treatment of ganciclovir-resistant human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) is the most frequent cause of infectious
      complications after whole organ transplantation. Ganciclovir is a nucleoside
      analogue of guanosine, and the first antiviral drug to be effective in the
      treatment of cytomegalovirus disease in humans. However, prolonged or repeated
      courses of ganciclovir predispose to the development of viral drug resistance.
      The isolation of a ganciclovir-resistant virus strain was first reported in 1989.
      Mutations in UL97 and DNA polymerase genes may induce resistance to the drug but
      lack of phosphorylation seems the most frequent mechanism of resistance in vivo.
      Most ganciclovir-resistant HCMV strains are susceptible to the pyrophosphate
      analogue foscarnet, which does not require activation and blocks the viral DNA
      polymerase by a noncompetitive mechanism. However, HCMV strains with multiple
      resistance to ganciclovir and other antiviral drugs have been described.

PMID- 9238623
TI  - Aplastic anemia due to B19 parvovirus infection in cadaveric renal transplant
      recipients: an underestimated infectious disease in the immunocompromised host.
AB  - Parvovirus B19 has been identified as the etiological agent of "fifth disease" in
      childhood. It is also a rarely reported cause of anemia in transplanted patients.
      During a period of 18 months we observed four cases (2 male and 2 female; 53 +/-
      4.24 years) of severe aplastic anemia due to parvovirus B19 in kidney transplant
      patients. The overall incidence of the disease was 6.3% of all our transplanted
      patients. Symptoms of the disease occurred 22.5 +/- 9.75 days post-operatively.
      Serum creatinine was 1.5 +/- 0.35 mg/dl. Hb was 6.58 +/- 0.6 g/dl. All patients
      recovered with 15 days of high doses of commercial immunoglobulins. We conclude
      that B19 parvovirus infection is probably an underestimated disease in transplant
      patients. It is a first-period infection, probably donor-transmitted. High dose
      immunoglobulins are an effective but costly therapy.

PMID- 9238624
TI  - N-3 polyunsaturated fatty acid supplementation in chronic progressive renal
      disease.
AB  - Chronic renal failure (CRF) may be accelerated by secondary lipid and immune
      abnormalities which could be antagonized by polyunsaturated fatty acid (PUFA). We
      examined 20 CRF patients on conservative treatment, randomized in two groups: G1
      consisted of 10 control patients and G2 10 patients supplemented for 12 months
      with a 3.4 g daily dose of PUFA. In basal conditions and after 12 months the
      following parameters were checked: creatinine clearance (CCr), daily urinary
      protein excretion per unit of residual renal function (UProt/CCr), rate of
      progression of renal insufficiency (delta CCr); triglycerides (TG), total (TC),
      HDL (HDALC) and LDL (LDLC) cholesterol, apolipoproteins Apo Al, Apo B,
      lipoprotein(a) Lp(a); lymphocyte subpopulations; spontaneous (c) and stimulated
      (s) cytokines IL-1 beta, IL-2, tumor necrosis factors TNF-alpha secretion by
      peripheral mononuclear cells. The groups did not differ in their basal
      parameters, which did not change in G1 during follow-up. In G2 the following
      parameters, initially higher than normal significantly decreased after 12 months:
      TG (2.9 +/- 0.45 to 2.6 +/- 0.3 mmol/l p < 0.005), Apo B (1.40 +/- 0.37 to 1.22
      +/- 0.36 g/l, p < 0.05), c TNF-alpha (1008.1 +/- 534.9 to 726.8 +/- 458.7 pg/ml,
      p < 0.05). Spontaneous (c) IL-1 beta (216.7 +/- 116.2 to 150.5 +/- 107.8 pg/ml, p
      < 0.05), c IL-2 (124.5 +/- 43.8 to 101.6 +/- 25.8 pg/ml, p < 0.05), and s TNF
      alpha (2456.4 +/- 908.3 to 1632.2 +/- 497.1 pg/ml, p < 0.005) also decreased,
      although already within the normal range at baseline. G2 patients experienced a
      steady monthly reduction of CCr whereas it rose progressively in G1 (p < 0.05),
      with a simultaneous increase in UProt/CCr (p < 0.05). PUFA are beneficial on the
      lipid and immune abnormalities secondary to CRF and may also have a useful effect
      on the progression of chronic renal damage.

PMID- 9238626
TI  - In search of dark horses: affinity maturation of phage-displayed ligands.
AB  - Most combinatorial libraries are 'sparse' in that only a tiny fraction of the
      relevant class of compounds is represented. This sparseness can be compensated in
      some measure by alternating rounds of selection with rounds of mutagenesis. Thus,
      clones are selected from the initial library by some criterion of 'fitness', such
      as affinity for a particular receptor. The selected clones are then mutagenized
      to generate a mutant library, which serves as input to the next round of
      selection, and so on. If the first round of selection is too stringent, rejecting
      all but the very fittest clone in the initial library (the 'initial champion'),
      we might miss 'dark horses': clones in the initial library that are inferior to
      the initial champion, yet can be mutated to even higher fitness than can that
      champion. A more thoughtful strategy is to alternate nonstringent selection with
      simultaneous mutagenesis of many selected-clones en masse.

PMID- 9238625
TI  - Renal abnormalities in patients with sickle cell-beta thalassemia.
AB  - We examined renal abnormalities in Greek patients with sickle-cell beta
      thalassemia (S-beta thal). A total of 17 patients aged 16-59 years suffering from
      S-beta thal and 17 age- and sex-matched healthy controls were studied. In all
      individuals we carried out a detailed study of renal function including
      electrolytes in serum and urine, concentrating or diluting ability, urine
      acidification ability, glomerular filtration rate (GFR), and hormones [such as
      plasma renin activity (PRA), serum aldosterone, and erythropoietin (EPO)]. Though
      the GFR did not differ significantly in patients and controls, half the patients
      had either supranormal or subnormal values. Serum potassium and uric acid were
      significantly higher in patients than controls. Serum phosphorus was similar in
      both groups, though patients with S-beta thal had significantly lower phosphate
      excretion indices. All patients were unable to maximally concentrate the urine,
      and seven also had limited ability to maximally dilute it. Five patients had
      incomplete distal renal tubular acidosis. Four had mild proteinuria, and six had
      microalbuminuria. Serum EPO and aldosterone were higher in S-beta thal patients
      than controls, but there was no difference in PRA between the two groups. There
      was a strong correlation between hemoglobin concentration and EPO levels, which
      was strongest in patients with GFR < 50 ml/min. We conclude that patients with S
      beta thal, like sickle-cell anemia patients, present multiple abnormalities of
      renal function.

PMID- 9238627
TI  - Binding properties of SH3 peptide ligands identified from phage-displayed random
      peptide libraries.
AB  - Combinatorial libraries have yielded high-affinity ligands for SH3 domains of a
      number of different proteins. We have shown that synthetic peptides containing
      these SH3 ligand sequences serve as specific probes of SH3 domains. Direct
      binding of the N-terminal biotinylated peptide ligands was conveniently detected
      in ELISA, filter-blotting, and dot-blotting experiments with the use of
      streptavidin-conjugated enzymes. In some cases, detection of peptide-SH3
      interactions required that the biotinylated peptides first were preconjugated
      with streptavidin to form a multivalent complex. Interestingly, these nominally
      tetravalent SH3 peptide ligands cross-react to varying degrees with different SH3
      domains. We have used such complexes to screen lambda cDNA expression libraries
      and have isolated clones that encode both known and novel SH3-domain-containing
      proteins. Based on the success of this methodology, we propose a general strategy
      by which ligands of a modular domain-containing protein can be isolated from
      random peptide libraries and used to screen cDNA expression libraries
      systematically for novel modular domain-containing proteins.

PMID- 9238628
TI  - Identification of peptide sequences that bind the Thomsen-Friedenreich cancer
      associated glycoantigen from bacteriophage peptide display libraries.
AB  - The goal of this study was to determine if polypeptides that bind specifically to
      the carcinoma-associated Thomsen-Friedenreich (T) antigen could be isolated from
      a random peptide bacteriophage display library. T antigen is a carbohydrate
      antigen that is exposed and immunoreactive on the surfaces of most primary
      carcinomas and their metastases, while it is masked on normal cells. Tumor
      specific surface carbohydrates are often used as markers of cell differentiation
      and play a role in cell aggregation, which is an important step in the metastatic
      process. Therefore, peptides that bind and mask T antigen may yield useful
      carbohydrate-specific probes and provide insight into carbohydrate-mediated tumor
      cell aggregation. A 15-amino acid random peptide bacteriophage display library
      was screened for polypeptides that exhibited high specificity to two
      glycoproteins which display T antigen on their surfaces. The results suggest that
      synthetic peptides identified from the bacteriophage display library have high
      affinities (Kd approximately 1 microM) and specificities for proteins and human
      tumor cells which present T antigen. Thus, random bacteriophage peptide display
      libraries may be a rich source of sequences that bind to carbohydrate antigen
      structures.

PMID- 9238629
TI  - The use of a combinatorial library method to isolate human tumor cell adhesion
      peptides.
AB  - Tumor cell progression is dependent in part on the successful adhesive
      interactions of the cells with the extracellular matrix. In this study, a new
      approach is described to isolate linear peptide ligand candidates involved in
      cellular adhesion. A synthetic combinatorial peptide library based on the 'one
      bead-one-peptide' concept was incubated with live human prostate cancer cells for
      90 min at 37 degrees C. The peptide bead coated with a monolayer of cells was
      then isolated for microsequencing. The DU145 (DU-H) cells were chosen since they
      have been previously characterized as containing elevated levels of a laminin
      receptor for cell adhesion, the alpha 6 beta 1 integrin on the cell surface. The
      use of a function-blocking antibody (GoH3) allows for the detection of peptides
      which are alpha 6-specific ligand candidates. From two different libraries
      (linear 9-mer and 11-mer) of a total of 1,500,000 beads, 68 peptide beads
      containing attached cells were isolated. These positive beads were then retested
      to determine the ability of the GoH3 antibody to block binding of the cells to
      the peptide beads. The alpha 6 integrin candidate peptide beads (five in total)
      were recovered and two of the beads were microsequenced. These two peptides, RU-1
      (LNIVS-VNGRHX) and RX-1 (DNRIRLQAKXX), resemble the previously reported active
      peptide sequences (GD-2 and AG-73) from native laminin. The RU-1, RX-1 and AG-73
      peptides were tested for their ability to support cell attachment and to bind the
      cell surface of DU-H prostate carcinoma cells in suspension using fluorescence
      activated cell-sorting (FACS) analysis. Both RU-1 and AG-73 peptides supported
      cellular attachment within 1 h. In contrast, after 1 h, EHS laminin supported
      both cellular attachment and spreading. The RX-1 peptide exhibited only weak
      binding to the DU-H prostate carcinoma cells. FACS analysis indicated that AG-73
      peptide attached to tumor cell surfaces over a range of concentrations, whereas
      the RU-1 peptide showed a homogeneous concentration required for attachment. The
      described strategy for screening a random peptide library offers three
      advantages: (i) ligands for conformationally sensitive receptors of adhesion can
      be isolated using live cells; (ii) specific binding can be selected for using
      function-blocking antibodies; and (iii) peptides supporting adhesion independent
      of spreading properties can be distinguished. In principle, specific adhesive
      peptides without prior knowledge of the sequence could be isolated for any
      epithelial cell surface receptor for which a function-blocking reagent is
      available.

PMID- 9238630
TI  - Exploring antibody polyspecificity using synthetic combinatorial libraries.
AB  - Extensive mapping studies for seven antigen-antibody interactions have been
      carried out using both individual analogs and peptide libraries. With competitive
      ELISA, these studies have revealed that monoclonal antibodies exhibit a broad
      range of specificities, from antibodies that recognize only conservative
      substitutions for 1-2 positions of the antigenic determinant, to antibodies that
      recognize sequences that are completely unrelated to the parent antigen with
      comparable affinities. Synthetic combinatorial libraries, containing millions of
      peptide sequences, permit a more systematic and rapid evaluation of the extent of
      multiple-binding specificities of monoclonal antibodies than individual analogs.
      The peptide libraries used here comprise mixtures of compounds having
      specifically defined positions and mixture positions. The same diversity of
      sequences in different formats, which differ by the numbers of positions
      singularly defined and different locations defined within the sequence, can be
      examined. Comparison of the screening results, selection criteria of the most
      active mixtures, and different approaches used for the deconvolution of active
      individual compounds are discussed. Synthetic combinatorial libraries greatly
      facilitate the understanding of antigen-antibody interactions at the amino acid
      level and will assist in the development of improved immunodiagnostics.

PMID- 9238631
TI  - Sequence-selective nonmacrocyclic two-armed receptors for peptides.
AB  - Tweezer-like receptor molecules have proven their potential for molecular
      recognition on several occasions. We decided to make twofold use of this receptor
      design: firstly to learn whether simple molecular forceps consisting of two
      peptide chains linked by a spacer are able to selectively bind to small peptides,
      and secondly to investigate the importance of structural preorganization for the
      characteristics of the receptors. We prepared two encoded combinatorial libraries
      based on this design, featuring two combinatorial tripeptide chains held by
      different scaffolds: the use of chenodeoxycholic acid as spacer provided a rigid
      scaffold for the forceps, whereas linking the peptide chains by a pentamethylene
      chain yielded a very flexible forceps structure. Molecules from the cholic acid
      library recognize and discriminate various enkephalins with micromolar
      affinities. Molecules from the flexible library show distinct interactions with
      the enkephalins as well, but the specificity and affinity are clearly diminished.
      Thus, although the interactions of molecular forceps with peptides are not
      crucially dependent on structural preorganization, receptors with a rigid design
      are clearly superior to flexible molecular forceps.

PMID- 9238632
TI  - Libraries from libraries: generation and comparison of screening profiles.
AB  - A positional scanning tetrapeptide library was chemically modified through
      alkylation and/or reduction of the amide bonds, thus generating three new
      combinatorial libraries with physico-chemical properties very different from the
      parent peptide library ('libraries from libraries'). Specific results were
      obtained with each of these libraries upon screening in kappa-opioid receptor
      binding and microdilution antimicrobial assays, illustrating the potential of the
      'libraries from libraries' concept for the efficient generation of a variety of
      chemically diverse combinatorial libraries.

PMID- 9238633
TI  - Design considerations and computer modeling related to the development of
      molecular scaffolds and peptide mimetics for combinatorial chemistry.
AB  - A critical issue in drug discovery utilizing combinatorial chemistry as part of
      the discovery process is the choice of scaffolds to be used for a proper
      presentation, in a three-dimensional space, of the critical elements of structure
      necessary for molecular recognition (binding) and information transfer (agonist/
      antagonist). In the case of polypeptide ligands, considerations related to the
      properties of various backbone structures (alpha-helix, beta-sheets, etc.; phi,
      psi space) and those related to three-dimensional presentation of side-chain
      moieties (topography; chi (chi) space) must be addressed, although they often
      present quite different elements in the molecular recognition puzzle. We have
      addressed aspects of this problem by examining the three-dimensional structures
      of chemically different scaffolds at various distances from the scaffold to
      evaluate their putative diversity. We find that chemically diverse scaffolds can
      readily become topographically similar. We suggest a topographical approach
      involving design in chi space to deal with these problems.

PMID- 9238634
TI  - High-volume cellular screening for anticancer agents with combinatorial chemical
      libraries: a new methodology.
AB  - A single-step cancer cell cytotoxic assay system for anticancer drug discovery
      has been developed which facilitates rapid screening of large combinatorial
      chemical libraries synthesized using the 'one-bead-one-compound' (OBOC)
      methodology. Each OBOC library bead incorporates two orthogonally cleavable
      linkers that release the bead-bound compound at a different pH. The assay
      utilizes high concentrations of tumor cells mixed directly with OBOC beads and
      plated in soft agarose containing tissue culture medium. One of the orthogonal
      linkers is cleaved at neutral pH in tissue culture releasing an aliquot of
      compound to diffuse at a relatively high local concentration into the soft
      agarose immediately surrounding the bead. Active compounds are identified
      visually from a clear ring of tumor cell lysis which forms within 48 h around
      just the rare bead releasing a cytotoxic compound. The bead releasing a cytotoxin
      is then plucked from the agar and the remaining compound still linked to the bead
      can be released for structural analysis, followed by compound resynthesis and
      confirmatory testing. This assay system has been successfully applied to
      identification of lead cytotoxic compounds from model peptidic and non-peptidic
      combinatorial chemical libraries. Use of this methodology may facilitate
      anticancer drug discovery.

PMID- 9238635
TI  - Optimization and visualization of molecular diversity of combinatorial libraries.
AB  - One of the major goals of rational design of combinatorial libraries is to design
      libraries with maximum diversity to enhance the potential of finding active
      compounds in the initial rounds of high-throughput screening programs. We present
      strategies to visualize and optimize the structural diversity of sets of
      molecules, which can be either potential substituents to be attached at specific
      positions of the library scaffold, or entire molecules corresponding to
      enumerated libraries. The selection of highly diverse subsets of molecules from
      the library is based on the stochastic optimization of 'Diversity' functions
      using a single-point-mutation Monte Carlo technique. The Diversity functions are
      defined in terms of the distances among molecules in multidimensional property
      space resulting from the calculation of 2D and 3D molecular descriptors. Several
      Diversity functions, including an implementation of D-Optimal design, are applied
      to select diverse subsets and the results are compared. The diversity of the
      selected subsets of molecules is visualized by embedding the intermolecular
      distances, defined by the molecules in multidimensional property space, into a
      three-dimensional space.

PMID- 9238636
TI  - Library generation through successive substitution of trichlorotriazine.
AB  - The decreasing reactivity of tri-, di- and monochlorotriazine was utilized for
      the solid-phase construction of a combinatorial library with three randomized
      positions, using 20 amino acids and 50 amines as building blocks. The first
      chlorine atom was selectively substituted by coupling a large excess of
      trichlorotriazine to the support-bound amino acid, thus avoiding simultaneous
      substitution of the second chlorine. The second and third diversity positions
      were selectively introduced by coupling amines at different temperatures.
      Mixtures of model compounds were synthesized and analyzed, showing the correct
      representation of all expected components. A library composed of 12,000 compounds
      was generated using this method.

PMID- 9238637
TI  - Design, synthesis and use of binary encoded synthetic chemical libraries.
AB  - With the advent of combinatorial chemistry a new paradigm is evolving in the
      field of drug discovery. The approach is based on an integration of chemistry,
      high-throughput screening and automation engineering. The chemistry arm is
      usually based on solid-phase synthesis technology as the preferred approach to
      library construction. One of the most powerful of the solid-phase methods is
      encoded split synthesis, in which the reaction history experience by each
      polymeric bead is unambiguously recorded. This split-and-pool approach, employing
      chemically robust tags, was used to construct a 85,000-membered dihydrobenzopyran
      library.

PMID- 9238639
TI  - Rationally designed non-peptides: variously substituted piperazine libraries for
      the discovery of bradykinin antagonists and other G-protein-coupled receptor
      ligands.
AB  - Molecular modeling studies of potent decapeptide bradykinin antagonists suggested
      the de novo design of peptide mimetics based on a 1,2,3,4-tetrasubstituted 1,4
      piperazin-6-one scaffold. These de novo-designed antagonists exhibited only
      modest potency (IC50 approximately 55 microM) on a cloned human B2 receptor and
      antagonist activity in an in vitro human-cell functional assay. The success of
      these structures led to the creation of prototype libraries based on variously
      substituted 1,4-piperazine scaffolds, which allowed a rapid and general search of
      pharmacophores attached to a piperazine scaffold. The parent piperazinedione
      structures and fully reduced piperazine libraries differ from recently reported
      diketopiperazine libraries in the use of diverse nonnatural amino acids, on-resin
      submonomer synthesis to provide more diverse N-substituted structures, and the
      adaptation of simultaneous ring closure and resin cleavage to drive the formation
      of highly hindered amide bonds. Using this chemistry, a rationally directed non
      peptide library of approximately 2500 N,N'-disubstituted piperazines and
      piperazinediones was synthesized and screened for ligand affinity on bradykinin,
      neurokinin, and opioid receptors. A number of lead structures were identified.
      Notably, a bradykinin antagonist lead, CP-2458, with good receptor selectivity
      and antagonist activity in human-cell assays was identified and is undergoing
      optimization by traditional and combinatorial methods.

PMID- 9238638
TI  - Liquid-phase combinatorial synthesis: in search of small-molecule enzyme mimics.
AB  - The applications, advantages and recent advances in liquid-phase combinatorial
      chemistry using poly-(ethyleneglycol) as a soluble polymer support are reviewed.
      Our recent efforts towards the synthesis of peptide-based catalysts on
      polyethyleneglycol are reported. The screening of libraries of peptides for
      catalysis is discussed.

PMID- 9238640
TI  - Screening chemical libraries for nucleic-acid-binding drugs by in vitro
      selection: a test case with lividomycin.
AB  - Screening new drugs is a costly and time-consuming process. Identifying new
      targets for existing therapeutics is often a particularly effective avenue for
      drug development. We have investigated whether in vitro selection can be used for
      target acquisition. Aminoglycoside antibiotics are known to bind to and
      inactivate functional natural nucleic acids, such as ribosomal RNA. As an example
      of how new targets for aminoglycosides could be identified, a lividomycin aptamer
      was iteratively isolated from a random sequence pool. The consensus sequence of
      this and other anti-aminoglycoside aptamers was used as the basis for a
      comprehensive search of natural sequence databases. Surprisingly, a high degree
      of similarity was found between aptamers and genomic sequences from a variety of
      organisms. While many of the similarities found are in regions of unknown or
      nonessential function, some of the sequences are found in critical genes in
      pathogenic organisms.

PMID- 9238642
TI  - Obtaining a family of high-affinity, high-specificity protein inhibitors of
      plasmin and plasma kallikrein.
AB  - Human lipoprotein-associated coagulation inhibitor (LACI) is a serum protein
      containing three Kunitz domains. We displayed the first domain (LACI-D1) on the
      III protein of phage M13 and made libraries of this domain. We iteratively varied
      13 residues in the region corresponding to the BPTI-trypsin interface and
      selected for binding to human plasmin (PLA) and human plasma kallikrein (pKAL).
      For PLA, our first-round best binder, EPI-P211, had KD = 2 nM. Using information
      from the first selection, we made a PLA-biased library containing approximately
      500,000 proteins and selected from these a protein, EPI-P302, having a KD for PLA
      of 87 pM. EPI-P302 inhibits pKAL with KD approximately 250 nM (approximately 2800
      fold higher than for PLA) and KD values for other proteases are higher yet. From
      the same initial LACI-D1 library, we selected an inhibitor of pKAL, EPI-K401,
      with a KD for pKAL of 287 pM. We used information from this selection to
      construct a pKAL-biased library from which we selected EPI-K502, which has a KD
      for pKAL of 40 pM. EPI-K502 inhibits PLA with KD approximately 20 nM (500-fold
      higher than for pKAL); KD values for other proteases are much higher. For both
      targets and for both selections, there are families of proteins having a few
      differences and a range of affinities for their targets. These proteins are
      candidate drugs and imaging agents for indications involving excess PLA or pKAL.
      Structure-activity relationships of PLA and pKAL binders will allow design of
      small molecules that are specific for these targets.

PMID- 9238643
TI  - Phosphorus-based combinatorial libraries: use of amino acid derivatives as
      synthons.
AB  - Phosphorus has been used as a scaffold to prepare combinatorial libraries of
      phosphoramidates in which one of the diversity elements resulted from derivatives
      of amino acids. A small library was prepared for analytical and characterization
      purposes, followed by a larger library of approximately 8800 compounds. Libraries
      were assembled on solid supports using the conventional pool-and-divide method,
      followed by cleavage from the supports at the end of the synthesis. Mass
      spectrometry was used to confirm that library synthesis had been successful.
      Individual compounds were also prepared to study the stability of compounds of
      this type.

PMID- 9238641
TI  - Tolerance of different proteins for amino acid diversity.
AB  - Random mutagenesis of genes followed by positive genetic selection in bacteria
      requires that the variant molecules confer biological activity, and is thus the
      most demanding approach for generating new functionally active molecules.
      Furthermore, one can learn much about the protein in question by comparing the
      population of selected molecules to the library from which they were selected.
      Described here is a mathematical method designed to guide such comparisons. We
      use as examples the results of randomization-selection studies of four different
      proteins. There exists, in general, a positive correlation between the number of
      amino acid substitutions in a critical region of a protein and the likelihood of
      inactivation of that protein; a correlation long suspected, but developed here in
      detail. At this time, we are comparing regions in different proteins and our
      conclusions must be limited. However, the method presented can serve as a
      guideline for anticipating the yield of new active mutants in genetic
      complementation assays based on the extent of randomization.

PMID- 9238644
TI  - Selection of a histidine-containing inhibitor of gelatinases through
      deconvolution of combinatorial tetrapeptide libraries.
AB  - A fully automated peptide synthesizer was used to generate tetrapeptide
      sublibraries from 24 natural and nonnatural amino acids, from which new
      inhibitors of gelatinases (matrix metalloproteinases MMP-2 and MMP-9) were
      selected as potential anticancer drugs. MMP-2 and MMP-9 from mouse Balbc/3T3
      fibroblasts conditioned media were assayed in their linear range response by
      zymography to quantify inhibition at each step of the tetrapeptide library
      deconvolution. The histidine-epsilon-amino caproic acid-beta-alanine-histidine
      (His-epsilon Ahx-beta Ala-His) sequence was found to yield optimal inhibition of
      both MMP-2 and MMP-9. Inhibition by selected tetrapeptides was also evaluated
      with two other techniques, a native type IV collagen degradation assay and a
      fluorogenic enzymatic assay, confirming the tetrapeptide potency. The His-epsilon
      Ahx-beta Ala-His tetrapeptide also inhibited purified human MMP-2 and MMP-9 and
      the corresponding enzymes present in conditioned media from human tumour cells.
      Finally, the length of the spacer between the two terminal histidines was found
      to be crucial to the inhibitory potential. This approach may thus be considered
      as a-successful strategy to yield specific peptide or pseudopeptide inhibitors,
      although their potency remains moderate, since it was measured before any
      chemical optimization was undertaken.

PMID- 9238646
TI  - Identification of new tag sequences with differential and selective recognition
      properties for the anti-FLAG monoclonal antibodies M1, M2 and M5.
AB  - The FLAG peptides DYKDDDDK and MDYKDDDDK are widely used affinity tags. Here we
      describe new variants of the FLAG peptides which, in direct ELISA, showed
      selective and differential binding to the commercially available anti-FLAG
      monoclonal antibodies M1, M2 and M5. Variants of the FLAG peptides were
      synthesized on polymer-grafted plastic pins, and in an ELISA incubated with mAbs
      M1, M2 and M5. Among the newly identified tag sequences are those that bind only
      one of the anti-FLAG mAbs and those that bind only two or all three of the anti
      FLAG mAbs. Examples of new tag sequences are MDFKDDDDK (which binds mAb M5 and
      does not bind mAbs M1 and M2) and MDYKAFDNL (which binds mAb M2 and does not bind
      mAbs M1 and M5). The sensitivity in direct ELISA of some variants was increased,
      e.g. using mAb M2 it was found that replacing DDDDK in MDYKDDDDK by AFDNL
      increased the sensitivity in ELISA at least 10-fold. The activity of this peptide
      was studied in more detail. In different direct ELISAs, in which MDYKAFDNL was
      synthesized on polyethylene pins, coated onto polystyrene microtiter plates or
      onto nitrocellulose paper, the activity of this peptide was similar, i.e.
      increased at least 10-fold over that of MDYKDDDDK. Remarkably, in competitive
      ELISA the binding activity of soluble MDYKAFDNL was decreased 10-fold over those
      of soluble MDYKDDDDK or DYKDDDDK. The results seem to suggest that, in solution,
      the conformation of MDYKAFDNL is more 'unstructured' compared to its conformation
      when coated or linked to a carrier. We postulate that the newly described tag
      sequences may be used as affinity tags to separately detect, quantify and purify
      multiple co-expressed proteins and/or subunits.

PMID- 9238647
TI  - Synthetic methods for polyamine linkers and their application to combinatorial
      chemistry.
AB  - Polyamines and polyamine conjugates display a diverse range of important
      biological functions, ranging from antibiotics to immunosuppressants and
      glutamate receptor antagonists. For these reasons, polyamines provide an
      excellent template/scaffold for combinatorial chemistry. In this paper we present
      methods for the solid-phase immobilisation of polyamines for use in synthetic and
      combinatorial chemistry and describe how they have been employed in the
      preparation of a number of important polyamine conjugates and polyamine
      libraries. Thus, we have designed, synthesised and utilised a number of polyamine
      linkers for both solution and resin screening combinatorial application.

PMID- 9238645
TI  - Optimization of the synthesis of peptide combinatorial libraries using a one-pot
      method.
AB  - Conditions for the synthesis of synthetic peptide combinatorial libraries (SPCLs)
      from mixtures of amino acids were explored. In a one-pot synthesis, the effect of
      the starting concentrations of amino acids on the resulting library composition
      was studied, and the optimum balance of amino acids was determined. Protein
      sequencing, MALDI-TOF, and amino acid analysis were used for the evaluation of
      the libraries, and their relative merits-are discussed. The effects of continuous
      flow automated synthesis instrumentation in conjunction with polyethylene glycol
      polystyrene (PEG-PS) graft supports and various cleavage cocktails on the
      successful synthesis of SPCLs were examined.

PMID- 9238648
TI  - Xanthines as a scaffold for molecular diversity.
AB  - Xanthines represent a new, versatile scaffold for combinatorial chemistry. A five
      step solid-phase synthesis of xanthine derivatives is described which includes
      alkylations, a nucleophilic displacement reaction at a heterocycle and a ring
      closure reaction by condensation of a nitroso function with an activated
      methylene group. The selected reaction sequence allows the production of a highly
      diverse small-molecule combinatorial compound library.

PMID- 9238649
TI  - Recent publications in solid-phase chemistry: Part 1.
AB  - Recent literature in solid-phase organic and inorganic chemistry has been
      reviewed. Papers have been collated according to the compounds prepared on the
      solid phase and the types of transformations performed. Covered are more than 40
      chemical transformations as well as the preparation of more than 50 functional
      groups.

PMID- 9238650
TI  - The receptor encoded by the human C-MET oncogene is expressed in testicular
      tissue and on human spermatozoa.
AB  - Because of its distinctive ability to act as a mitogen, a mitogen and a
      morphogen, hepatocyte growth factor/scatter factor (HGF/SF) has all the
      characteristics of a molecule able to function in regulatory networks of
      motility, such as the spermatogenic epithelium, and this through binding of its
      receptor p190MET (C-MET). In this study we report the expression of C-MET in the
      human seminiferous epithelium and on spermatozoa from men being treated for
      infertility and sperm donors. The presence of C-MET was demonstrated by
      immunochemistry on the cell membrane of spermatogonia, spermatocytes, spermatids
      and on spermatozoa, whereas Sertoli cells and Leydig cells did not show
      expression. Comparison of C-MET expression on spermatozoa of the 90% Percoll
      layer of subfertile patients and donors revealed clearly two distinct groups
      (unpaired t-test, P < 0.001), whereas comparison of C-MET expression on
      spermatozoa in the 47% Percoll layer was not significantly different between
      patients and donors. In addition, there was a significant inverse correlation
      between sperm concentration and the C-MET expression of spermatozoa in the 90%
      Percoll layer (r = -0.80, 95% confidence interval, -0.92 to -0.55; P < 0.0001),
      but not with the C-MET expression of spermatozoa in the 47% Percoll layer. In
      conclusion, the presence of C-MET was demonstrated in the seminiferous epithelium
      and on mature and immature spermatozoa, indicating a role for this growth factor
      receptor in the differentiation and/or migration that occurs during human
      spermatogenesis.

PMID- 9238652
TI  - Measurement of intracellular pH in human spermatozoa by flow cytometry with the
      benzo[c]xanthene dye SNAFL-1: a novel, single excitation, dual emission,
      molecular probe.
AB  - In numerous animal species the acrosome reaction of spermatozoa has been linked
      to elevations in intracellular pH (pHi). However, whether or not this is merely a
      passive consequence of calcium ion influx is not known. Studies into the
      fluctuations in pHi in sperm cells have been hampered by the lack of a pH
      sensitive probe that could be used in conjunction with flow cytometry. In this
      study, flow cytometric analysis of pHi in human spermatozoa was accomplished by
      using one of the new benzo[c]xanthene dyes (SNAFL-1). SNAFL-1 was then observed
      in situ with conventional fluorescent microscopy and was found to be located in
      the post-acrosomal cytoplasm of the head. It was then used to measure the
      differences in pHi between acrosome intact populations of spermatozoa, and
      populations that had been induced to acrosome-react with human follicular fluid
      or the calcium ionophore A23187 to mimic the calcium influx. It was concluded
      that the human sperm acrosome reaction is also accompanied by a rise in pHi and
      the natural agonist-induced rise could not be accounted for by calcium ion influx
      alone.

PMID- 9238651
TI  - CD52 is the 'major maturation-associated' sperm membrane antigen.
AB  - The 'major maturation-associated' sperm membrane antigen is the most prominent
      glycopeptide which appears on the surface of rat spermatozoa during post
      testicular sperm maturation. The name describes the fact that its occurrence
      coincides with the spermatozoa acquiring their major physiological properties of
      maturation in the distal epididymis. It is shown in this study that this
      phenomenon is not restricted to the rat. Rather, by immunohistochemical staining,
      in-situ transcript hybridization and molecular analyses of genomic DNA fragments
      it is evident that homologous counterparts exist in other mammalian species,
      including the human. The human homologue is an abundant epididymal gene product
      that has previously been identified as lymphocyte surface antigen CD52. Thus,
      following the human standard nomenclature, it seems more appropriate to refer to
      these molecules as CD52 homologues. Localization of the mRNA for these
      glycosylphosphatidyl inositol (GPI)-anchored glycopeptides within the epididymal
      epithelium, and not within the testis, suggests that they may be transferred from
      epididymal to sperm cell with their GPI-anchor intact.

PMID- 9238653
TI  - Effect of gonadotrophin on cell and matrix retention and expression of
      metalloproteinases and their inhibitor in cultured human granulosa cells
      modelling corpus luteum function.
AB  - Granulosa cells were prepared from follicular aspirates obtained at oocyte
      collection for in-vitro fertilization (IVF) and maintained in culture.
      Substantial loss of cells from the culture surface occurred in the absence of
      gonadotrophin when cells were maintained on a thin layer of extracellular matrix
      (ECM) using a defined, serum-free medium. This cell loss was clearly and
      significantly reduced in the presence of human chorionic gonadotrophin (HCG) by
      days 4-6 of culture, and occurred in conjunction with loss of ECM. Analysis of
      culture medium by zymography using gelatin as substrate demonstrated the presence
      of metalloproteinases (MMP), MMP-9 (gelatinase B) appearing as the predominant
      band. Measurement of overall gelatinase activity in culture media revealed a
      progressive fall in gelatinase expressed on a per cell basis in media from HCG
      treated cultures and this was less marked in controls. This suppression of
      gelatinase activity was consistent with an observed increase in production of
      tissue inhibitor of metalloproteinase-1 (TIMP-1) by HCG-treated cells, which was
      significant by days 6-8 of culture. We speculate that stabilization of the ECM
      may be an important aspect of HCG action in the corpus luteum.

PMID- 9238654
TI  - Expression of heparin-binding epidermal growth factor messenger RNA in the human
      endometrium.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member
      of the epidermal growth factor family. In rodents HB-EGF has been found to
      mediate the mitogenic effects of oestrogen on the endometrial glandular cells and
      those of progesterone on the stromal cells. HB-EGF has also been found to be
      expressed at the site of implantation before any other discernible sign of
      blastocyst attachment in rodents. Our aim was to determine whether HB-EGF mRNA
      was expressed in the human pregnant and non-pregnant endometrial tissues. Normal
      endometrial tissues at different stages of the menstrual cycle, first trimester
      chorionic villi and decidua, second trimester chorionic villi and term placental
      tissues were snap frozen and stored at -80 degrees C. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to analyse the expression of HB-EGF
      mRNA in these tissues. HB-EGF mRNA was found to be expressed in human endometrium
      throughout the menstrual cycle. It was also present in first trimester chorionic
      villi and decidua, second trimester villi and term placenta. These findings
      suggest that HB-EGF may have a role in the growth or function of the human
      uterus, and that it may be important at the feto-maternal interface throughout
      pregnancy.

PMID- 9238655
TI  - Localization of bradykinin type II receptor mRNA in human endometrium.
AB  - Bradykinin is a nonapeptide inflammatory agent that in the endometrium stimulates
      stromal cell proliferation, prostaglandin synthesis and electrogenic ion
      transport. The expression of bradykinin type II (B2) receptor mRNA was examined
      by in-situ hybridization using 35S-labelled riboprobe in human endometrium to
      determine its temporal and spatial pattern of distribution throughout the
      menstrual cycle. The B2 receptor mRNA was expressed in proliferative and
      secretory endometrium. In the early proliferative endometrium there were low
      levels of B2 receptor mRNA over both the glands and stromal cells. The signal
      increased in intensity and was localized over the glands with low levels of
      hybridization in the stroma in the late proliferative endometrium. In the early
      secretory endometrium B2 receptor mRNA was highly expressed in the endometrial
      glands. The strong hybridization signal persisted and in late secretory
      endometrium both glandular and stromal cells expressed B2 receptor mRNA. The
      apparent increase in B2 receptor mRNA in the secretory endometrium suggests that
      bradykinin acting via B2 receptor may play a role in the increased vascular
      permeability and vasodilatation associated with implantation.

PMID- 9238656
TI  - Interleukin-8 concentration in peritoneal fluid of patients with endometriosis
      and modulation of interleukin-8 expression in human mesothelial cells.
AB  - Interleukin-8 (IL-8) is a chemoattractant and activating factor for human
      neutrophlls and a potent angiogenic agent. The peritoneal fluid of women with
      endometriosis has been shown to have increased neutrophil chemotactic activity.
      We postulate that IL-8 may be an important modulator in the pathogenesis of
      endometriosis and adhesion formation. We first investigated IL-8 concentrations
      in the peritoneal fluid of women with or without endometriosis, then assessed
      peritoneal mesothelial cells as a potential source of peritoneal fluid IL-8.
      Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to
      investigate IL-8 mRNA and protein modulation. The mean concentration of IL-8 in
      samples obtained from control patients (n = 28) was 4.8 +/- 0.5 pg/ml; from
      patients with minimal-mild endometriosis (n = 24) was 27.5 +/- 2.6 pg/ml; and
      from patients with moderate-severe endometriosis (n = 21) was 530.2 +/- 65.1
      pg/ml. Confluent mesothelial cells were incubated with human recombinant IL-1
      alpha (0.01-100 IU/ml) or tumour necrosis factor (TNF)-alpha (0.01 to 100 ng/ml)
      for 2-24 h. IL-8 mRNA was detectable in non-treated cells, however both IL-1
      alpha and TNF-alpha induced higher amounts of IL-8 mRNA in a dose- and time
      dependent manner. Non-treated mesothelial cells in culture also produced and
      secreted IL-8 protein quantified by ELISA, but again higher concentrations were
      induced by IL-1 alpha and TNF-alpha treatment. In conclusion, we found that IL-8
      concentrations were elevated in peritoneal fluids from women with endometriosis.
      Cultured mesothelial cells expressed cytokine-inducible IL-8 mRNA and secreted IL
      8 protein. The regulated expression of this angiogenic factor may play a role in
      pathogenesis of endometriosis.

PMID- 9238657
TI  - DNA repair by oocytes.
AB  - Experimental evidence in a number of different in vivo and in vitro systems
      indicates clearly that the vertebrate oocyte is capable of repairing endogenous
      and exogenous DNA damaged as a result of meiotic recombination, the action of UV
      and X-irradiation or the effects of mutagenic chemicals. It would appear that
      both before and after the dictyate stage of meiosis the oocyte has less repair
      capacity and/or is more sensitive to DNA damaging agents. Epigenetic factors
      associated with the expression of genetic faults arising in oocytes have been
      largely ignored in the past. It is probable that attention to such factors, will
      in the future, lead to a better appreciation of the capacity of oocytes to repair
      genetic damage. Non-disjunctional events are particularly prone to occur in
      dictyate oocytes. Oxygen deprivation, perturbations of microtubular structure by
      temperature and other factors appear to have disastrous cytogenetic consequences
      at this otherwise resistant resting stage.

PMID- 9238658
TI  - Complement-binding proteins are strongly expressed by human preimplantation
      blastocysts and cumulus cells as well as gametes.
AB  - Human preimplantation embryos, gametes and cumulus cells were studied for
      expression of the complement-binding proteins CD46 (membrane cofactor protein),
      CD55 (decay accelerating factor) and CD59 (membrane attack complex inhibitory
      factor) as well as complement receptors type 1 (CRI), type 2 (CR2) and type 3
      (CR3). Both the CD55 and CD59 glycosyl phosphatidylinositol (GPI)-anchored
      proteins were expressed by the plasma membrane and zona pellucida of oocytes,
      early embryos and expanded preimplantation blastocysts; in contrast, CD46 was
      expressed only on the plasma membrane. Cumulus cells consistently expressed CD46
      and, most strongly, CD59 whereas CD55 expression was variable. Monoclonal
      antibodies (mAbs) to CRI, CR2 and CR3 epitopes gave only occasional reactivity on
      oocytes and were unreactive with blastocysts, spermatozoa and cumulus cells. CD46
      is expressed only on the spermatozoal inner acrosomal membrane, and CD59 on the
      plasma membrane; CD55 expression was confirmed on the plasma membrane as well as
      the inner acrosomal membrane. Control mAbs specific for factor H were usually
      unreactive with gametes, blastocysts and cumulus cells. These data support the
      concept that gametes and early embryonic cells are protected from complement
      mediated attack by expression of CD46, CD55 and CD59, although these complement
      binding proteins may have additional roles in reproductive events.

PMID- 9238659
TI  - Management of rhesus isoimmunization by preimplantation genetic diagnosis.
AB  - A genetic assay by single blastomere analysis was developed for rhesus (RhD)
      blood group typing of early cleavage stage embryos. The method, which is based on
      the simultaneous amplification of an RhD-specific sequence and an internal
      control in single cells, was applied for the selective transfer of RhD-negative
      embryos in a family of an RhD sensitized woman and a heterozygote partner. The
      RhD status of two out of three biopsied embryos was determined. According to
      their amplified products, both were typed as RhD-negative and transferred to the
      uterus. Pregnancy was not achieved.

PMID- 9238660
TI  - Nuclear structural conditions and PCR amplification in human preimplantation
      diagnosis.
AB  - An understanding of the relationship between nuclear morphology and DNA function
      is important in cytology and preimplantation diagnosis. In this study, direct
      polymerase chain reaction (PCR) amplification was used to diagnose the common
      delta F508 mutation of cystic fibrosis in 62 biopsied human embryo cells. The
      nuclei were photographed and classified into three categories depending on their
      microscopic appearance; these were further correlated with the results of PCR
      amplification. The normal nucleus group (42 embryo cells, with clear and regular
      nuclear membrane, transparent nucleoplasm and prominent nucleoli) showed 100% PCR
      amplification, with normal amplification results, i.e. bright DNA bands. These
      were considered to be the living cells. Only half of the cells (10 embryo cells)
      which contained abnormal nuclei (with abnormal nuclear membranes or nucleoplasm)
      showed PCR amplification, often with abnormal amplification results, i.e. weak
      DNA bands. These cells were considered to be either degenerate or to be
      undergoing degeneration. The anuclear cells (10 embryo cells) were composed of
      living (metaphase) and degenerated cells and showed about 30% PCR amplification.
      These results demonstrated that one of the important signs of early visible cell
      degeneration is the partial or total degeneration of the nucleus. Abnormal
      morphological changes of the nuclear membrane and nucleoplasm are usually
      accompanied with functional and structural DNA alteration. It is suggested that
      base degradation occurs earlier than the breakage of base-sugar bonds and
      phosphodlester bonds during the course of DNA degradation. The selection of
      optimal cells with a normal nucleus for single cell embryo biopsy is important
      for the precision and safety of preimplantation diagnosis.

PMID- 9238661
TI  - Microsatellite instability in aborted embryos.

PMID- 9238662
TI  - Germline gene therapy: its time is near.

PMID- 9238663
TI  - The signals and molecular pathways involved in human menstruation, a unique
      process of tissue destruction and remodelling.
AB  - Human endometrium is a specialized tissue that undergoes sequential phases of
      proliferation and secretory changes in order to support the implantation and
      growth of an embryo. If implantation does not occur, this tissue rapidly
      undergoes dissolution during the menstrual period. Tissue shedding during
      menstruation is associated with significant apoptosis, disordered expression of
      adhesion molecules, loss of filamentous (F) actin from cell borders and
      fragmentation of endometrial glands. On the other hand, compromise of integrity
      of vessels and dissolution of the extracellular matrix leads to bleeding and
      tissue dissolution. The processes of bleeding and tissue shedding during
      menstruation are precisely controlled by a number of systemic and local factors.
      The systemic signal that leads to menstruation is the withdrawal of the steroid
      hormones. The available evidence suggests but does not yet prove that tumour
      necrosis factor (TNF)-alpha may serve as the local signal contributing to the
      processes of menstrual shedding and bleeding. Secretion of metalloproteinases and
      their subsequent activation induced by plasmin facilitates degradation of
      extracellular matrices and bleeding. The menstrual process ceases by secretion of
      steroid hormones directly or through regulation of production or activation of
      signals that lead to tissue shedding and bleeding.

PMID- 9238664
TI  - Programmed cell death and human embryo fragmentation.
AB  - The quality of embryos produced by in-vitro fertilization (IVF) is variable. Many
      embryos contain unequal sized blastomeres and multiple cellular fragments.
      Embryos with excessive fragmentation have limited developmental potential both in
      vitro and in vivo. Histologically, some blastomeres of fragmented embryos
      resemble cells undergoing apoptosis as a result of programmed cell death (PCD).
      The objective of the present study was to determine if the morphological features
      of apoptosis are observed in fragmented human preimplantation embryos, supporting
      the possible involvement of PCD in early human embryo arrest and demise. Using
      combined nuclear and terminal transferase-mediated DNA end labelling (TUNEL) on
      arrested, fragmented human embryos, we were able to detect extensive condensation
      and degradation of chromatin, compatible with apoptosis. Electron microscopy
      confirmed the typical morphological features of apoptosis. No such abnormalities
      were observed in spare embryos with regular sized blastomeres without
      fragmentation. The high incidence of condensed chromatin, TUNEL detection of
      degraded DNA, cell corpses and apoptotic bodies in fragmented human embryos
      strongly suggest that PCD is triggered in human embryos at a stage prior to
      blastocyst formation. At such early stages, occurrence of apoptosis seemed to be
      detrimental, leading to preimplantation embryo death.

PMID- 9238665
TI  - Preliminary studies on the role of plasminogen activator in seminal plasma of
      human and rhesus monkey.
AB  - Two types of plasminogen activators (PA), tissue type (tPA) and urokinase type
      (uPA), were identified in the seminal plasma of both the human and the rhesus
      monkey. We studied the possible relationship between PA activities in the seminal
      plasma and the sperm counts and motility and demonstrated that: (i) PA activity
      in human seminal plasma from infertile patients was associated with immotile
      spermatozoa; (ii) the treatment of fertile men with testosterone enanthate (TE)
      to induce azoospermia was accompanied by an increase in seminal PA activity;
      (iii) when monomer T4 (isolated from multiglycosides of Tripterygium wilforddi)
      was administered to fertile male rhesus monkeys to induce azoospermia, PA
      activities in seminal plasma increased considerably; and (iv) immunocytochemistry
      studies showed that both uPA and PAI-1 antigens were localized on the surface of
      human spermatozoa, indicating that human spermatozoa were capable of binding uPA
      and PAI-1 through their receptors or forming a complex. These data demonstrate
      that seminal PA activity may be related to azoospermia, and possibly, to the
      fertilizing capability of spermatozoa in primates.

PMID- 9238666
TI  - Adenosine modulation of neurotransmission in human uterine arteries.
AB  - The relaxing effects of adenosine, N-[(R)-1-methyl-2 phenylethyl]-adenosine (R
      PIA) and 5-N-ethylcarboxamide adenosine (NECA) were investigated in human uterine
      arteries precontracted by phenylephrine in vitro. Adenosine, R-PIA and NECA
      relaxed isolated uterine arteries with intact endothelium, the potency order was
      NECA > R-PIA > adenosine. When tested on vessels devoid of their endothelium, the
      relaxing effect of adenosine was the same. These results suggest the
      vasodilatation effect on human uterine arteries is endothelium-independent, and
      might be via the A2 receptor (by pharmacological classification). By
      administering adenosine to human uterine arterial cell culture, single cell
      intracellular calcium change was also determined by laser cytometry. Decreased
      intracellular calcium was observed after administration of adenosine 10(-6) M and
      2 x 10(-6) M. We concluded from the results that adenosine acts on human uterine
      artery cell by A2 receptor, independently of the endothelium, and decreases the
      intracellular calcium concentration, thus causing uterine artery relaxation.

PMID- 9238667
TI  - Regulation of the inducible form of prostaglandin endoperoxide synthase in the
      perfused rat ovary.
AB  - The regulation of the two isoforms of prostaglandin endoperoxide synthase (PGS-1
      and PGS-2) and prostaglandin synthesis by luteinizing hormone (LH)/3-isobutyl-1
      methylxanthine (IBMX) and progesterone was examined in granulosa cells and
      residual ovarian tissue of rat ovaries perfused in vitro. The endogenous
      progesterone synthesis was blocked by an inhibitor of 3 beta-dehydroxysteroid
      dehydrogenase, compound A (CA), previously shown to reversibly inhibit ovulation
      in the in vitro perfused rat ovary. Preovulatory ovaries were perfused for 7 h,
      and soluble extracts from granulosa cells and residual ovarian tissue were
      obtained for immunoblotting and determination of the tissue contents of PGS-1/PGS
      2. The tissue concentrations of prostaglandins (PGE2, PGF2 alpha and 6-keto-PGF1
      alpha) were measured. The ovaries were perfused with medium alone (control) or
      medium containing LH (0.1 microgram/ml) and IBMX (0.2 mM), LH+IBMX+CA (10
      micrograms/ml) or LH+IBMX+CA+progesterone (10 micrograms/ml). PGE2, PGF2 alpha
      and 6-keto-PGF1 alpha tissue concentrations were increased by LH+IBMX, with
      highest values detected for PGE2. The addition of CA alone or CA in combination
      with exogenous progesterone, did not change the values of prostaglandins
      increased by LH+IBMX. The content of PGS-1 was only marginally changed in both
      granulosa cells and residual ovarian tissue in the different treatment groups,
      compared to the control group. In contrast, PGS-2 was markedly increased by
      LH+IBMX, especially in the granulosa cells. The addition of CA, in combination
      with LH+IBMX, resulted in a small decrease of PGS-2, and progesterone further
      decreased its content. In the residual ovarian tissue, only minor changes of PGS
      2 were detected. These results demonstrate that LH and progesterone selectively
      regulate the expression of PGS-2 in rat granulosa cells, whereas the hormonal
      regulation of PGS-1 is less pronounced. Progesterone inhibits PGS-2 in granulosa
      cells but has negligible effects on the total ovarian synthesis of prostaglandins
      during the ovulatory period.

PMID- 9238668
TI  - GnRH receptor mRNA expression by in-situ hybridization in the primate pituitary
      and ovary.
AB  - Gonadotrophin-releasing hormone (GnRH) receptors are present on the ovary as well
      as in the anterior pituitary gland. GnRH analogues may exert their actions in
      part via these ovarian receptors. However, in the primate ovary, GnRH receptors
      are of low affinity and their significance is questionable. The aim of the
      present study was to compare pituitary and ovarian expression of the GnRH
      receptor mRNA by in-situ hybridization to gain further information on the
      possible significance of the ovarian receptor. Pituitaries and ovaries were
      obtained from two stump-tailed macaque monkeys and three marmoset monkeys at the
      mid-luteal phase of the ovulatory cycle. Human corpora lutea were obtained during
      the early and mid-luteal phase and after 'rescue' by human chorionic
      gonadotrophin (HCG) and a whole ovary obtained during the late luteal phase (n =
      1 per group). Frozen tissue sections were incubated with a 33P-labelled probe to
      the human GnRH receptor and exposed for 4 weeks. All pituitary glands exhibited
      intense silver grains in the anterior pituitary gland. In the ovaries, grains
      were present at low levels in the granulosa cells of antral follicles, just above
      tissue background in corpora lutea and indistinguishable from tissue background
      in the remaining ovarian compartments. These results demonstrate that the GnRH
      receptor mRNA in the primate pituitary is present in sufficient quantities to be
      clearly detectable in the anterior pituitary gland by in-situ hybridization. In
      contrast, in the human and monkey, ovary levels of mRNA appear to be very low.

PMID- 9238669
TI  - Nuclear retinoid receptor expression in normal human endometrium throughout the
      menstrual cycle.
AB  - Previous work has shown that retinoic acid receptors (RARs) and retinoid X
      receptors (RXRs) are expressed in human endometrial epithelial and stromal cells.
      These nuclear receptors mediate the biological effects of retinoic acid, a
      vitamin A derivative which may have an important, though poorly characterized
      role in the functional differentiation of secretory epithelia. The aim of this
      study was to find out whether the expression of RAR and RXR mRNA in endometrial
      epithelial and stromal cells varies in relation to the menstrual cycle. The
      expression of RARs and RXRs was investigated by Northern blotting and, for
      stromal cells, there were no differences in expression of RAR-alpha, RAR-beta,
      RAR-gamma and RXR-alpha between the proliferative and secretory phases of the
      menstrual cycle. Similarly, for epithelial tissue, there were no significant
      differences between the proliferative and secretory phases with respect to the
      expression of RAR-alpha, RAR-gamma and RXR-alpha. However, RAR-beta was expressed
      at a 1.7-fold higher level in epithelial samples from the proliferative phase
      compared to the secretory phase. Overall, the levels of expression of RAR-alpha,
      RAR-beta and RAR-gamma were 1.7- to 4-fold higher in stromal cells compared to
      epithelial cells whereas RXR-alpha was expressed at a similar level in both cell
      types. We have previously suggested that retinoic acid has a role in endometrial
      differentiation or function which may be reflected by cyclical changes in
      intracellular retinoic acid levels. These data indicate that RARs and RXRs are
      expressed at a similar level throughout the menstrual cycle, with the possible
      exception of RAR-beta, implying that any menstrual cycle-related function of RARs
      in controlled by ligand availability rather than by changes in expression of the
      receptors.

PMID- 9238670
TI  - Identification of a Gly862 to Ser substitution in the type I collagen gene from a
      single spermatozoon.
AB  - Individual spermatozoa from the father of two affected infants with osteogenesis
      imperfecta were separated by dilution and micromanipulation. A segment of the
      type I collagen gene containing the mutant region was amplified by nested
      polymerase chain reaction and sequenced. Among 40 individual spermatozoa, 15
      specimens were identified as mutants with a substitution of guanine3208 to
      adenine (glycine862 to serine) while 18 and seven specimens were of the wild and
      mixed types respectively. Through this study, we have established a molecular
      procedure that can be considered as prerequisite for preimplantation diagnosis of
      genetic disorders with a single point mutation.

PMID- 9238671
TI  - The PRINS technique: potential use for rapid preimplantation embryo chromosome
      screening.
AB  - The primed in-situ labelling (PRINS) method is an alternative to in-situ
      hybridization for chromosomal detection based on the use of chromosome-specific
      oligonucleotide primers. Using this process, we have developed a simple and semi
      automatic method for rapid in-situ detection of human chromosomes. The reaction
      was performed on a programmable temperature cycler. Specific labelling was
      obtained in < 2 h reaction. Double PRINS techniques were performed on six
      morphologically abnormal preimplantation embryos using primers specific for
      chromosomes 9, 16, 18, 21, X and Y. The majority of these embryos displayed
      chromosomal abnormalities. The present results demonstrate that PRINS may be a
      simple and reliable technique applicable in human preimplantation diagnosis.

PMID- 9238672
TI  - Chromatin packaging and morphology in ejaculated human spermatozoa: evidence of
      hidden anomalies in normal spermatozoa.
AB  - This study aimed to investigate the association between anomalies in sperm
      chromatin packaging, morphology and fertilization in patients undergoing routine
      in-vitro fertilization (IVF) or subzonal insemination (SUZI). Sperm chromatin
      packaging was assessed using chromomycin A3 (CMA3), a fluorochrome specific for
      guanine-cytosine rich sequences of DNA. One hundred to 150 sperm cells were
      assessed in 55 patients to compare sperm chromatin packaging and morphology to
      fertilization after IVF or SUZI. When the morphology and CMA3 fluorescence of
      individual spermatozoa was assessed, > 75% of the macrocephalic sperm fluoresced
      in all patients. In contrast, a mean of 37% of the spermatozoa with normal
      morphology fluoresced in IVF patients compared with 58% of the normal spermatozoa
      in male factor patients treated by SUZI. SUZI patients displaying a high
      fluorescence (> 70%) in their spermatozoa also had a significantly lower
      fertilization rate. Lower packaging quality in morphologically normal spermatozoa
      may represent a major limiting factor in the fertilizing ability of male factor
      patients. This study confirms that a high percentage of CMA3 positivity is
      present in certain forms of male factor infertility and that such a test may be
      used to distinguish separate populations in morphologically normal spermatozoa.

PMID- 9238673
TI  - Vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with the
      N314D mutation of galactose-1-phosphate uridyl transferase (GALT).
AB  - To follow-up our previous observation that vaginal agenesis might be associated
      with decreased activity of galactose-1-phosphate uridyl transferase (GALT), we
      studied activity and genotype of GALT in 13 daughters with vaginal agenesis and
      their mothers. For comparison, GALT measurements were available from 113 pre
      menopausal women with no known Mullerian anomalies selected from the general
      population. Red cell GALT activity was significantly lower in both the daughters
      and their mothers in comparison with general population controls. Six out of
      thirteen (46%) daughters and two mothers of the remaining seven daughters (29%)
      were carriers for the N314D mutation of GALT associated with the Duarte variant
      of galactosaemia as compared to 16 out of 113 general population controls (14%)
      who possessed at least one N314D allele. Pigmentary skin changes and scoliosis
      were associated phenotypic findings in daughters with vaginal agenesis. We
      conclude that fetal or maternal GALT mutations that decrease GALT activity may be
      associated with vaginal agenesis and have, as their possible biological basis,
      increased intrauterine exposure to galactose which has been demonstrated in
      rodents to cause decreased oocyte survival and delayed vaginal opening in
      offspring.

PMID- 9238674
TI  - Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl
      transferase (GALT).
AB  - To explore a possible connection between endometriosis, Mullerian anomalies, and
      possession of the N314D allele of the gene for galactose-1-phosphate uridyl
      transferase (GALT), we studied 33 women with endometriosis attending a fertility
      clinic. Patients completed questionnaires and had DNA tested for the N314D
      mutation of GALT. A previously completed general population survey of 111 women
      which obtained the same information was available for comparison. Women with
      endometriosis were more likely to carry at least one N314D allele (30% compared
      with 14%) and more likely to report a medical history of scoliosis (21% compared
      with 2%) compared to general population controls: two features we have described
      in women with vaginal agenesis. Compared with endometriosis cases without the
      N314D allele, those cases with the allele tended to have more advanced disease
      and a family history of endometriosis. We speculate that endometriosis may arise
      due to defects of canalization of the cervix leading to cervical stenosis and
      retrograde menstruation. The relevance of the N314D mutation, via this model, may
      derive from an association between abnormalities of galactose metabolism and
      vaginal agenesis which represents a canalization defect of the vaginal plate of
      the Mullerian tubercle, the same structure which gives rise to the cervix.

PMID- 9238675
TI  - Integrins and human reproduction.

PMID- 9238676
TI  - The expression of alpha v, alpha 5, beta 1, and beta 3 integrin chains on
      ejaculated human spermatozoa varies with their functional state.
AB  - Evidence has been presented suggesting the involvement of integrins and their
      ligands in mammalian fertilization. In this study we asked whether the alpha 5,
      alpha v, beta 1 and beta 3 integrin chains, which form receptors for fibronectin
      and vitronectin, are present on human spermatozoa. Fresh ejaculate spermatozoa
      and capacitated spermatozoa, before and after a calcium ionophore (A23187)
      induced acrosome reaction, were either fixed and their reaction with anti
      integrin monoclonal antibodies detected by immunoperoxidase staining or studied
      without fixation, using cytofluorimetric scanning. Expression of specific
      integrin chains varied with the functional state of spermatozoa. The alpha 5
      chain was not detected on fresh living spermatozoa, but was present on
      capacitated spermatozoa, whether fixed or living. The pattern of beta 1
      expression on living spermatozoa paralleled that of alpha 5. No further increase
      in the expression of either alpha 5 or beta 1 was observed following an ionophore
      promoted acrosome reaction. In contrast, alpha v was detected on neither fresh,
      living ejaculate spermatozoa, nor following capacitation (< 10% reactive). The
      percentage of alpha v positive cells increased substantially following ionophore
      exposure. Expression of beta 3 was similar to alpha v, and the percentage of
      cells displaying beta 3 correlated with the proportion of spermatozoa that had
      undergone an acrosome reaction, following ionophore exposure. These results
      indicate that the expression of integrins on spermatozoa is dynamic, varying with
      their functional state and that integrin receptors for fibronectin (alpha 5 beta
      1) become apparent on the spermatozoan surface during capacitation and
      vitronectin (alpha v beta 3) following the acrosome reaction.

PMID- 9238677
TI  - Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins
      during sperm maturation.
AB  - In spermatozoa, as in other eukaryotic cells, integral membrane proteins may be
      anchored by a hydrophobic protein domain, or by a glycosylphosphatidylinositol
      (GPI) lipid anchor. Contrary to the current understanding of sperm membrane
      biogenesis, recent evidence shows that some of the GPI-anchored proteins are not
      synthesized by the spermatozoa themselves, but by cells of the male genital
      tract. They are transported to the fluid secretions, possibly associated with
      membrane vesicles, and then incorporate into the sperm membrane. This novel
      mechanism, by which proteins can move from the membrane of one cell to that of
      another in vivo, may account for a significant proportion of the surface changes
      occurring during sperm maturation. The function of these GPI-anchored molecules
      is largely unknown. However, they are remarkably abundant, and the phenomenon of
      cell-to-cell transfer seems to be well conserved across mammalian species. All of
      the post-testicularly acquired GPI-anchored proteins identified thus far have
      also been found on cells of the immune system (CD62, CD55, CD59, CD73), and we
      speculate that they may have a role in protecting spermatozoa from immune attack
      in the male and female reproductive tracts.

PMID- 9238678
TI  - Retinoic acid suppresses in-vitro decidualization of human endometrial stromal
      cells.
AB  - All-trans retinoic acid (RA) has potent effects on cell differentiation and gene
      expression. Previous studies have demonstrated that human endometrial stromal
      cells express mRNA for retinoic acid receptors (RARs) and cellular RA-binding
      protein-II (CRABP-II). We examined whether RA regulates stromal cell
      differentiation (decidualization), a critical process in preparation of the
      uterus for blastocyst implantation. Decidualization was induced by incubating
      cultured stromal cells with medroxyprogesterone acetate (MPA) and oestradiol.
      Decidualization was defined by the induction of prolactin, insulin-like growth
      factor binding protein-1 (IGFBP-1), appearance of a differentiated phenotype and
      changes in fibronectin expression. RA treatment significantly (P < 0.05)
      suppressed prolactin and IGFBP-1 production associated with stromal cells
      decidualization. The formation of differentiated cells was inhibited by RA, and
      consistent with maintenance of the undifferentiated phenotype, fibronectin mRNA
      content was approximately 3.5-times greater than in the absence of RA. Upon
      induction of decidualization, the expression of mRNA for the major RA receptor
      sub-types (RAR-alpha, -beta and -gamma) was maintained while the relative amounts
      of CRABP-II mRNA progressively decreased with differentiation. With RA treatment,
      RAR-alpha and RAR-gamma mRNA concentrations were approximately 70 and 25%
      respectively of those in cells decidualized in the absence of RA. The effects of
      RA appear to be partially mediated by inhibition of cAMP action. RA suppressed
      intracellular cAMP concentrations induced by MPA and oestradiol to approximately
      35% of those in cells without RA. Addition of 50 microM dibutyryl cAMP to stromal
      cells treated with MPA and oestradiol only partially reversed the suppression of
      decidualization and prolactin release by RA. In summary, we have demonstrated
      that in-vitro decidualization of human endometrial stromal cells induced by MPA
      and oestradiol treatment is suppressed by RA.

PMID- 9238679
TI  - Molecular approaches to the diagnosis of male infertility.
AB  - The introduction of the polymerase chain reaction (PCR) as a technique to
      selectively amplify and identify specific DNA and RNA sequences has
      revolutionized the field of molecular medicine. Application of these newly
      developed molecular techniques to the field of male infertility has made the
      delineation of subtle causes of infertility-an inapparent genital tract
      infection, immune system activation within the genital tract, mutations in sperm
      mitochondrial or chromosomal DNA, alterations in sperm components involved in
      receptor-ligand interactions, and production of sperm autoantibodies-all
      increasingly amenable to clinical analysis. Continued investigations at the
      molecular level of the causes of male infertility will also lead to novel
      treatment regimens as well as development of new methods of fertility regulation.

PMID- 9238680
TI  - Identification of the five most common cystic fibrosis mutations in single cells
      using a rapid and specific differential amplification system.
AB  - We describe a rapid and specific differential amplification system which can
      detect five of the most common cystic fibrosis mutations from a single cell. In
      the first round of the polymerase chain reaction (PCR), regions of exons 4, 10
      and 11 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene
      containing the mutations delta F508, G551D, R553X, G542X and 621+1G > T were co
      amplified in a single multiplex PCR. To identify potential contamination, we
      included external amplification primers for the polymorphic human tyrosine
      hydroxylase (HUMTH01) locus as a fingerprint for the sample. In the second round
      of PCR, detection of any of the five mutations was achieved using the
      amplification refractory mutation system (ARMS) in two separate reactions, each
      containing nested amplification primers for either wild type or mutant sequence.
      A separate second round PCR for the fingerprinting was performed with nested
      HUMTH01 primers. Using this procedure we have successfully and accurately
      detected five cystic fibrosis mutations in 30 single cells with a failed
      amplification rate of 7% and a contamination rate of 4.6% and that PCR failure or
      possible contamination will also be easily detected. This procedure allows
      detection of the five most common point mutations and small deletions responsible
      for cystic fibrosis from a single cell in < 8 h which could be applicable to
      preimplantation diagnosis in human embryos.

PMID- 9238681
TI  - Adaptation of the primer extension preamplification (PEP) reaction for
      preimplantation diagnosis: single blastomere analysis using short PEP protocols.
AB  - Primer extension preamplification (PEP) was first described as a method for whole
      genome amplification, starting from a single cell, originally a spermatozoon, in
      order to perform genetic recombination studies. Its usefulness for
      preimplantation diagnosis was shown soon after; the only drawback was the length
      of the procedure (> 14 h). We have developed a shorter PEP protocol for single
      human blastomeres, enabling us to examine several genetic loci of interest in
      human genetic diseases with a good amplification efficiency.

PMID- 9238682
TI  - Increasing the denaturation temperature during the first cycles of amplification
      reduces allele dropout from single cells for preimplantation genetic diagnosis.
AB  - Single cell polymerase chain reaction (PCR) for preimplantation genetic diagnosis
      (PGD) needs to be highly efficient and accurate. In some single cells from human
      embryos presumed to be heterozygous for the delta F508 deletion causing cystic
      fibrosis (CF), we recently observed random amplification failure of one of the
      two parental alleles following nested PCR. To investigate allele dropout (ADO),
      we have examined two different lysis protocols and the effect of altering the
      denaturation temperature in the primary PCR using single lymphocytes heterozygous
      for delta F508 or for two beta-thalassaemia mutations IVS 1 nt 1 (G/T) and 5
      (G/C) using a nested PCR protocol to amplify the 5' region of the beta-globin
      gene. Amplification rates were high after lysis in either water or lysis buffer
      and at all denaturation temperatures studied (> or = 92%). With a typical
      denaturation temperature (93 degrees C), ADO was detected at both loci. When the
      denaturation temperature was lowered to 90 degrees C, however, ADO increased
      substantially and conversely by raising the denaturation temperature to 96
      degrees C during the first 10 cycles ADO was reduced but not eliminated. ADO was
      also reduced with cells in lysis buffer. We suggest that ADO may be caused by a
      combination of inefficient denaturation and degradation of one of the genomic
      alleles in the first cycles of PCR. For autosomal recessive conditions in which
      both parents are carrying the same mutation, ADO would not cause serious
      misdiagnosis. For compound heterozygotes or autosomal dominant conditions,
      however, extensive testing of the amplification protocol with single heterozygous
      cells and individual calibration of each thermocycler for the effect of
      denaturation temperature on ADO is essential before clinical application.

PMID- 9238683
TI  - Internal pH of human spermatozoa: effect of ions, human follicular fluid and
      progesterone.
AB  - The internal pH (pHi) of human spermatozoa was measured by the fluorescent
      indicator 2,7-bicarboxyethyl-5,6-carboxyfluorescein acetoxymethyl ester (BCECF
      AM) and the distribution of the radioactive [14C]-methylamine under different
      external ionic conditions. The effect of the addition of progesterone and human
      follicular fluid (HFF) on the spermatozoa pHi was also analysed. The pHi values
      obtained were almost identical with the two probes used. In sodium (NaM) and
      potassium (KM) media, a linear relationship between the internal and external pH
      was observed. In NaM, the pHi values were approximately 0.4 pH unit less than the
      external pH. In KM, the pHi measured was higher than in NaM and only slightly
      inferior to the external pH (0.1-0.2 pH unit). Addition of 10 microM
      progesterone, oestradiol 17 beta or 20% HFF to spermatozoa incubated at pH 7.2 in
      NaM did not induce any rapid variation of the BCECF fluorescence or change in the
      accumulation of methylamine. A slight change in pH (approximately 0.5 units)
      occurred with progesterone after 15 min. As a control, addition of 10 mM of NH4Cl
      induced a rapid alkalinization (0.4 pH unit) of the cell interior while 10 mM
      lactate produced only a slight acidification (approximately 0.2 pH unit). Under
      the same conditions (NaM, pH 7.2), the pHi of the spermatozoa prepared by Percoll
      gradient was found more acidic by 0.2 pH unit than washed unfractionated
      spermatozoa. Progesterone, oestradiol 17 beta and HFF had no effect on the pHi of
      these spermatozoa. The results obtained in this study show that it is possible to
      measure accurately the internal pH of human spermatozoa. Internal pH was found to
      be dependent upon the pH of the external medium and a quasi-linear relationship
      exists between the internal and external pH, suggesting no specific pH regulatory
      mechanisms. Our data suggest instead that the protons, under our experimental
      conditions, are passively distributed. Progesterone, oestradiol 17 beta and HFF,
      known to promote both capacitation and the acrosome reaction, do not act through
      a rapid pHi change.

PMID- 9238684
TI  - Single cell analysis of tyrosine kinase dependent and independent Ca2+ fluxes in
      progesterone induced acrosome reaction.
AB  - In this study we developed a single cell analysis protocol with which protein
      tyrosine kinase (PTK)-dependent and independent Ca2+ fluxes occurring in human
      spermatozoa in response to progesterone were evaluated. By recording the
      fluorescence emitted by fluo-3-loaded spermatozoa using a confocal laser scanning
      microscopy system it was possible not only to monitor relative changes in the
      intracellular free Ca2+ concentration ([Ca2+]i) but also to determine the time at
      which the acrosomal exocytosis began. The addition of progesterone produced a
      rapid transient [Ca2+]i increase in 35% of spermatozoa. In approximately 10% of
      spermatozoa, this initial [Ca2+]i increase was followed by a secondary [Ca2+]i
      increase beginning 2-10 min after the progesterone addition and leading to the
      acrosomal exocytosis in most of these spermatozoa. On the other hand, a rapid
      triggering of exocytosis during the initial [Ca2+]i increase was a relatively
      infrequent observation. The inhibition of PTK with genistein or herbimycin A did
      not influence the initial progesterone-induced [Ca2+]i increase but inhibited the
      secondary [Ca2+]i increase and the ensuing acrosomal exocytosis. The initial PTK
      independent Ca2+ response could be induced by progesterone in both non
      capacitated and capacitated spermatozoa, whereas the ability to generate the
      secondary, PTK-dependent response developed during in-vitro capacitation.

PMID- 9238685
TI  - Immunohistochemical detection of cathepsin D in endometrium from long-term
      subdermal levonorgestrel users and during the normal menstrual cycle.
AB  - A previous report has shown that progesterone up-regulates cathepsin D expression
      in human endometrial cell culture. In women using the levonorgestrel-releasing
      Implant Norplant, the plasma levonorgestrel and immunoreactive endometrial
      progesterone receptor concentrations are elevated. However, the functional status
      of these receptors is not known. This study used endometrial cathepsin D
      expression both as an indirect marker for the functional status of endometrial
      progesterone receptors, and to identify the cell types that express cathepsin D.
      The results show that cathepsin D is primarily found in glandular epithelia and
      luminal epithelia in control and Norplant endometria. There is no significant
      difference in cathepsin D expression between the control and Norplant endometria,
      between the various stages of the menstrual cycle, or between Norplant users with
      varying degrees of breakthrough bleeding. Cathepsin D is also detected in cells
      scattered in the stroma in both control and Norplant endometria. The majority of
      these cells are macrophages. These data indicate that there is no evidence for
      progesterone regulation of cathepsin D in the human endometrium. Cathepsin D thus
      cannot be used as a marker for the functional status of progesterone receptors
      found in the Norplant-exposed endometrium.

PMID- 9238686
TI  - Distribution of interleukin-6 in maternal and embryonic tissues during the first
      trimester.
AB  - Interleukin-6 (IL-6) distribution was investigated in coelomic fluid, amniotic
      fluid, maternal serum, decidua and placental villous tissue collected from 16
      normal pregnancies between 7 and 12 weeks of gestation. IL-6 levels in fluids and
      tissues were measured by an immunoenzymatic assay and mouse monoclonal antibodies
      specific for IL-6 were used to localize immunohistochemically IL-6 in decidual
      and placental tissue. IL-6 was detected in all samples of coelomic and amniotic
      fluids and in most extracts of placental and decidual tissues. IL-6 concentration
      was significantly (P < 0.005) higher in the coelomic fluid than in amniotic fluid
      and was positively correlated with gestational age. Immunostaining for IL-6 was
      present in both syncytiotrophoblast and extra-villous trophoblast. IL-6 was in
      significantly (P < 0.001) higher concentration in decidual than in placental
      tissues. These data indicate that IL-6 is normally present in coelomic and
      amniotic fluids of early pregnancy and that IL-6 concentrations mainly result
      from the accumulation of trophoblastic-derived IL-6. During the first trimester
      IL-6 could play a role in tissue remodelling associated with placentation but
      also in the haematopoiesis function of the secondary yolk sac and in the
      generation of new vessels in placental villous tissue.

PMID- 9238687
TI  - The human preovulatory follicle is a source of the chemotactic cytokine
      interleukin-8.
AB  - Mammalian ovulation has several similarities to local inflammatory reactions,
      involving participation of leukocytes and inflammatory mediators. In response to
      a preovulatory luteinizing hormone surge, there is an influx of leukocytes into
      the preovulatory follicle and uncharacterized chemotactic activity towards these
      cells has previously been reported in follicular fluid of several species,
      including the human. In the present study, we have investigated the presence and
      local production of interleukin-8 (IL-8), a potent leukocyte-chemotactic and
      neutrophil-activating cytokine, in the human preovulatory follicle.
      Immunoreactive IL-8 was present in the follicular fluid in all of 12 in-vitro
      fertilization (IVF) patients investigated. IL-8 concentrations in follicular
      fluid (1269 +/- 245 pg/ml) were approximately 30-fold higher than in plasma (41
      +/- 14 pg/ml). Isolated granulosa cells in culture secreted large amounts of IL-8
      protein. Basal secretion of IL-8 was dose-dependently enhanced by the presence of
      fetal calf serum and was further stimulated by the addition of the ovulation
      associated cytokine IL-1 beta. Messenger RNA for IL-8 was detected by reverse
      transcription/polymerase chain reaction (RT-PCR) in all tested samples of
      granulosa cells of IVF patients (n = 8) and in all biopsies from preovulatory
      follicle walls obtained in natural cycles (n = 6). This is the first
      demonstration of IL-8 in the mammalian ovary. Local production, combined with
      high follicular fluid concentrations, suggests that this cytokine plays a role in
      cyclic ovarian events, such as ovulation.

PMID- 9238688
TI  - Cell shape change reveals the cyclic AMP-mediated action of follicle stimulating
      hormone, human chorionic gonadotrophin and vasoactive intestinal peptide in
      primary cultured human granulosa-lutein cells.
AB  - Granulosa cells are known to be the site of action of various hormones and agents
      that regulate ovarian function. This study was conducted to evaluate the effects
      of gonadotrophins, vasoactive intestinal peptide (VIP), prostaglandin (PG) F2
      alpha and angiotensin II on the cyclic AMP (c-AMP) signalling transduction
      pathway in human granulosa-lutein cells. Exposure to agents that elevate c-AMP or
      mimic c-AMP action caused the cells to become rounded in a process that was rapid
      and reversible. We were able to demonstrate this cell rounding process in the
      presence of gonadotrophins and VIP, but not in the presence of PGF 2 alpha or
      angiotensin II. In addition, incubation of the cells with various selective
      phosphodiesterase (PDE) inhibitors revealed that the PDE type IV isoform, but not
      type III, catalyses c-AMP degradation in human granulosa-lutein cells. Alteration
      in c-AMP-dependent cytomorphology appears to be a convenient method to analyse
      the regulation of c-AMP-mediated events in the human granulosa-lutein cells.

PMID- 9238689
TI  - Gonadotrophin-releasing hormone and triptorelin inhibit the follicle stimulating
      hormone-induced response in human primary cultured granulosa-lutein cells.
AB  - Cyclic AMP (c-AMP)-dependent cell shape changes can be used to study the
      gonadotrophin response in cultured human granulosa-lutein cells. The same
      approach has been developed here to determine the direct potential
      antigonadotrophic effect of gonadotrophin-releasing hormone (GnRH) and a GnRH
      agonist (triptorelin) on human granulosa-lutein cells. Treatment with triptorelin
      or GnRH alone for 1 h did not affect granulosa-lutein cell morphology. However,
      in the presence of stimulatory doses of follicle stimulating hormone (FSH),
      triptorelin (5 x 10(-7)-5 x 10(-6) M) and GnRH (10(-11)-10(-9) M) inhibited the
      FSH-induced c-AMP-dependent response. The antigonadotrophic effect of triptorelin
      was prevented by two GnRH antagonists, indicating that triptorelin acts via
      specific GnRH binding sites. On the other hand, triptorelin failed to inhibit
      human chorionic gonadotrophin- and forskolin-mediated morphological changes. Our
      results suggest that the GnRH agonist interacts specifically with the FSH-induced
      c-AMP-dependent cascade of events, at a site located ahead of that of c-AMP
      generation. In conclusion, GnRH and triptorelin strongly inhibit FSH-mediated
      function in human granulosa-lutein cells in culture. This inhibition might play a
      role in the low follicular development rates observed in some patients treated
      with GnRH agonist + gonadotrophins for ovarian stimulation.

PMID- 9238690
TI  - The role of ryanodine-sensitive Ca2+ stores in the Ca2+ oscillation machine of
      human oocytes.
AB  - This study was undertaken to localize ryanodine-sensitive Ca2+ stores in human
      oocytes and to evaluate their role in the Ca2+ oscillations responsible for
      oocyte activation at fertilization. The addition of ryanodine provoked a Ca2+
      discharge from stores localized throughout the ooplasm with the exception of the
      cortical and subcortical peripheral regions. The ryanodine-induced discharge was
      typically followed by a short series of Ca2+ oscillations that only involved the
      cytoplasmic region populated by the ryanodine-sensitive stores. In contrast, the
      Ca2+ oscillations induced by the thiol reagent thimerosal or by spermatozoa at
      fertilization were of a much longer duration and also involved ryanodine
      insensitive stores. Presumably, these ryanodine-insensitive stores are sensitive
      to inositol 1,4,5-trisphosphate (InsP3). The addition of ryanodine to oocytes
      during ongoing thimerosal- or sperm-induced Ca2+ oscillations inhibited the
      oscillations. These data suggest a co-operation between the ryanodine-sensitive
      and ryanodine-insensitive stores in maintaining the sperm-induced Ca2+
      oscillations. In this two-store oscillation model, each periodic [Ca2+]i increase
      is triggered by a Ca2+ discharge from the peripheral, InsP3-sensitive stores
      inducing Ca(2+)-induced Ca2+ release from the ryanodine-sensitive stores.
      However, the pacemaker frequency of the Ca2+ discharges from the InsP3-sensitive
      stores is conditioned by the actual physiological state of the ryanodine
      sensitive stores.

PMID- 9238691
TI  - Expression of urokinase-type plasminogen activator in human preimplantation
      embryos.
AB  - During embryo implantation in the human trophoblast cells invade the endometrium
      and plasminogen activators (PA) are implicated in this tissue invasion process.
      Our studies on surplus embryos from patients undergoing in-vitro fertilization
      (IVF) treatments showed that PA activity was present in secretions of blastocysts
      but not embryos at the 2-4-cell stage. The secretion of this PA activity by
      blastocysts was increased by the addition of epidermal growth factor (EGF) to the
      embryo cultures. This PA activity had a molecular weight similar to that of
      urokinase-type PA (uPA). The mRNA for uPA was present in blastocysts, as
      determined by the reverse-transcription and polymerase chain reaction (RT-PCR)
      technique. These data indicate that uPA is produced by human preimplantation
      embryos and may play a role in early human development and embryo implantation.

PMID- 9238692
TI  - Rearrangements of the high mobility group protein family genes and the molecular
      genetic origin of uterine leiomyomas and endometrial polyps.
AB  - The results of cytogenetic studies of uterine leiomyomas have revealed that
      approximately 50% of these tumours are characterized by clonal chromosomal
      alterations. These karyotypic deviations are dominated by rearrangements
      involving a particular part of chromosome 12, i.e. region 12q13-15. We recently
      showed that the multiple aberration region on chromosome 12q15 harbours recurrent
      breakpoints frequently found in a variety of benign solid tumours. Within this
      region a gene encoding for a member of the so called high mobility group family
      proteins (HMG) was mapped. Further investigation revealed that this gene i.e.
      HMGI-C is often truncated by the chromosomal aberrations and fused to ectopic DNA
      sequences leading to fusion genes. Therefore, the results suggest a causal
      relationship between mutations of the HMGI-C gene and the development of uterine
      leiomyomas. Apparently identical mutations have been found also in endometrial
      polyps. Furthermore, there is an obvious coincidence between the chromosomal
      assignment of other members of the HMG family and the breakpoints of other non
      random chromosome abnormalities seen in uterine leiomyomas.

PMID- 9238693
TI  - Cell recycling of a single human cell for preimplantation diagnosis of X-linked
      disease and dual sex determination.
AB  - We recently described a new procedure, called 'cell recycling', which combines
      the two powerful techniques of polymerase chain reaction (PCR) and fluorescent in
      situ hybridization (FISH) on the same single fixed cell. The dual procedure was
      developed to single cell sensitivity using single blastomeres of preimplantation
      mouse embryos. We have now extended the procedure to single human cells and
      demonstrated its potential use in preimplantation diagnosis to detect Duchenne
      muscular dystrophy (DMD) by PCR, in addition to sexing the same single cell by
      both PCR and FISH. Here we report an efficiency of 65% for cell recycling with
      efficiencies for PCR ampification of a single copy DMD sequence at 87% and sexing
      by FISH at 75%. Should PCR diagnosis of the DMD mutation fail, cell recycling
      would provide two opportunities to identify the sex of the embryo, allowing
      selection of only the female embryos for transfer.

PMID- 9238694
TI  - Action of recombinant follicle stimulating hormone in superfused human granulosa
      cells in vitro.
AB  - The aim of this work was to compare the action of recombinant follicle
      stimulating hormone (rFSH) and urinary FSH (uFSH). Moreover we aimed to compare
      the secretory efficiency of continuous versus pulsatile stimulation by rFSH in
      superfused human luteal cells. Progesterone concentration was measured in culture
      medium by radioimmunoassay. Action of rFSH and uFSH was compared in static
      cultures of human granulosa cells at doses of 0.001-10 IU/ml. The secretory
      efficiency of both rFSH and uFSH was found to be similar in a defined range of
      concentrations (0.001-0.3 IU/ml). At concentrations of 1 and 10 IU/ml, the action
      of uFSH was significantly more potent than rFSH, up to 139% (P < 0.01) and 133%
      (P < 0.01) respectively. A concentration of 0.3 IU/ml of rFSH was most potent in
      static cultures, and evoked progesterone release up to 80 mg/ml. For a
      stimulation period of up to 4 h, the action of rFSH and uFSH in human granulosa
      cells was time-dependent and differences between them were not significant.
      Irregularities were observed at > 4 h stimulation time. In another experiment, in
      superfused human granulosa cells, we showed that the stimulatory effectiveness of
      pulsatile rFSH administration (time interval 60 min, application time 10 min) was
      greater for progesterone release (3973 ng of progesterone/1 IU rFSH) than was
      continuous administration (848 ng of progesterone/1 IU rFSH). In conclusion, the
      secretory action of rFSH is similar to that of uFSH for defined times and doses.
      Moreover, pulsatile rFSH administration is more efficient at stimulating the
      release of progesterone than continuous administration.

PMID- 9238695
TI  - Genomic imprinting abnormalities: a new potential risk of assisted reproduction.

PMID- 9238696
TI  - The timing of pronuclear formation, DNA synthesis and cleavage in the human 1
      cell embryo.
AB  - The timing of pronuclear formation and breakdown, DNA synthesis and cleavage
      during the first cell cycle of human embryogenesis are described. Pronuclei
      formed between 3 and 10 h post-insemination (hpi; median 8 hpi). S-phase
      commenced between 8 and 14 hpi, and was completed between 10 and 18 hpi. M-phase
      was observed between 22 and 31 hpi (median duration 3 h), and cleavage to the 2
      cell stage took place between 25 and 33 hpi. The timing of the same events was
      determined in 1-cell embryos derived from re-inseminated human oocytes that had
      failed to fertilize during therapeutic in-vitro fertilization (IVF). In these
      embryos, pronuclei formed between 3 and 8 h post-re-insemination (hpr-i),
      coinciding with the beginning of S-phase. While S-phase was completed as early as
      10 hpr-i in some embryos, it extended until at least 16 hpr-i in others.
      Pronuclear breakdown and cleavage occurred from 23 and 26 hpr-i respectively;
      however, they did not occur in some embryos until after 46 hpr-i. The results
      demonstrate a markedly greater degree of variation in the timing of these events
      in embryos derived from re-inseminated oocytes compared with embryos derived from
      conventional IVF, and thus throw into question the validity of using the former
      as models for studies of the first cell cycle of human embryogenesis.

PMID- 9238698
TI  - A role for diacylglycerol in human sperm acrosomal exocytosis.
AB  - Using human spermatozoa stimulated with either progesterone or the Ca2+ ionophore
      A23187 to undergo acrosomal exocytosis, we have investigated potential pathways
      for generation of diacylglycerol (DAG) and have examined the possibility that DAG
      plays an important role in the exocytotic response. Both treatments resulted in
      rapid and considerable generation of DAG, followed by a limited rise in
      phosphatidic acid (PA). Further experiments indicated that phospholipase C (PLC)
      activity is important in this generation of DAG, but phospholipase D activity
      probably is not. In addition, polyphosphoinositide-specific phosphoinositidase C
      activation and hydrolysis, of phosphatidylinositol 4,5-bisphosphate appears to be
      a necessary prerequisite for activation of the PLC pathway. Finally the DAG
      formed appears to be important in acrosomal exocytosis: (i) blocking DAG
      metabolism with a DAG kinase inhibitor resulted in both increased endogenous
      levels of DAG and a significantly increased exocytotic response in stimulated
      cells and (ii) exogenous DAG induced exocytosis in capacitated spermatozoa
      whereas PA did not. Taken together, these results suggest that DAG plays a key
      role in events leading to membrane fusion during human sperm acrosomal exocytosis
      stimulated by natural agonists.

PMID- 9238697
TI  - Detection of apoptosis in human endometriotic tissues.
AB  - To clarify whether apoptosis is involved in endometriosis, we obtained eutopic
      endometrial tissues along with endometriotic tissues from the uterus
      (adenomyosis) (n = 12) and from the ovary (n = 12) from patients undergoing
      gynaecological surgery. Apoptosis-induced DNA fragmentation was detected by the
      TdT-mediated dUTP-biotin nick-end labelling method, and immunostaining with a
      monoclonal antibody against the Fas, Le(y) or B-cell leukaemia/lymphoma-2 (bcl-2)
      was also performed using the same tissue section. Analysis showed that apoptosis
      was occurring in all the samples of ovarian endometriotic tissue but in only two
      of the 12 adenomyotic and in five of the 24 eutopic endometrial tissue samples.
      In none of these cases was apoptosis correlated with phases of the menstrual
      cycle. The expression of bcl-2 in the eutopic endometrial and adenomyotic tissues
      was limited to the proliferative phase, and was observed in only one of the 12
      cases of ovarian endometriosis. Fas and Ley were expressed randomly across a wide
      range in both the eutopic and ectopic endometrial tissues. These results suggest
      that the features of ovarian endometriosis are different from those of
      adenomyosis and eutopic endometrium in terms of the involvement of apoptosis. In
      addition, the regulatory mechanism involved in ovarian endometriosis may differ
      from that in other endometrial cells.

PMID- 9238699
TI  - Interference with follicle stimulating hormone regulation of human ovarian
      function.
AB  - This review summarizes observations on the background and potential clinical
      significance of interference with follicle stimulating hormone (FSH) regulation
      of human ovarian function. This interference may occur at the level of the
      pituitary by the secretion of FSH isoforms with reduced or absent bioactivity. In
      addition, interference with FSH may occur in the circulation, or within the
      ovarian follicular compartment. Although the full range of its significance
      remains to be elucidated, there are distinct indications that these mechanisms
      may be involved in normal ovarian physiology, as well as in abnormal response of
      the ovary to stimulation by endogenous FSH or by exogenously-administered
      gonadotrophin preparations. Moreover, recent advances in the determination of the
      structure-function relationship of FSH and FSH-receptor interaction, in
      combination with new developments in recombinant DNA technology, will allow the
      production of modified FSH- or FSH receptor-like molecules with altered
      bioactivity. The availability of FSH agonists and antagonists in the near future
      should provide a challenge for clinicians to improve treatment outcome and to
      find new indications for the use of these compounds.

PMID- 9238701
TI  - P-selectin is expressed on the oolemma of human and hamster oocytes following
      sperm adhesion and is also detected on the equatorial region of acrosome-reacted
      human spermatozoa.
AB  - Selectins are a family of adhesive molecules, involved in the interactions
      between leukocytes and endothelium and in platelet adhesion. P-selectin, one of
      the members of this family, is stored in alpha-granules and dense granules of
      platelets as well as in Weibel-Palade bodies of endothelial cells, and it is
      rapidly redistributed to the cell surface after activation. It recognizes
      carbohydrate structures as ligands, in particular sialyl-Lewis(x), which is part
      of the CD15 antigen. In this work we studied P-selectin expression on gametes.
      While zona-free human and hamster oocytes did not react with a monoclonal
      antibody directed against P-selectin, oocytes from both species displayed a
      reactivity with this antibody following their contact with human spermatozoa, as
      demonstrated both by covasphere binding and indirect immunofluorescence.
      Artificial activation of zona-intact human oocytes by means of the calcium
      lonophore A23187 induced the expression on the oolemma of a moiety reacting with
      anti-P-selectin antibody as well. P-selectin also appeared to be expressed on the
      sperm surface following the acrosome reaction, as demonstrated by a flow
      cytometric study of reactivity of spermatozoa with the anti-P-selectin antibody,
      using the expression of CD46 as a marker of the acrosome reaction. The
      localization of the P-selectin moiety on the equatorial region of the plasma
      membrane of acrosome reacted spermatozoa was confirmed by transmission electron
      microscopy using immunogold labelling. We suggest that P-selectin might be
      involved in gamete interactions.

PMID- 9238700
TI  - Low expression of adhesion molecules and matrix proteins in patients showing poor
      penetration in zona-free hamster oocytes.
AB  - The expression of adhesion molecules and matrix proteins by human spermatozoa as
      well as their binding to and penetration of zona-free hamster eggs were
      investigated in 17 patients by means of flow cytometry. Both binding and
      penetration of hamster oocytes and expression of alpha- and beta-chains of beta
      1, beta 3 and beta 4 integrins were determined before and after induction of the
      acrosome reaction. The expression of the integrin ligands, fibronectin and
      laminin were also analysed. Significant differences in the expression of very
      late antigen (VLA) integrins, VLA alpha 4-chain (CD49d), the classical
      fibronectin receptor VLA alpha 5-chain (CD49e), leukocyte function-associated
      molecule-3 (LFA-3; CD58) and fibronectin were observed between patients showing
      good (> 10%) or poor (< 10%) penetration in the sperm penetration assay (P =
      0.0068). It is concluded that these adhesion molecules are intimately involved in
      the sperm-oolemma interaction. Since no differences were observed in either
      spermiogram parameters or the percentages of acrosome-reacted spermatozoa in the
      two groups, sperm-oolemma binding and penetration should be regarded as discrete
      parameters of sperm function.

PMID- 9238702
TI  - Sperm centrosome dysfunction: a possible new class of male factor infertility in
      the human.
AB  - This study examined the normality of microtubule growth and aster development
      from the sperm centrosome in failed fertilizations and pronuclear-arrested eggs
      after intracytoplasmic insemination with spermatozoa derived from severe
      oligoteratozoospermic individuals. In these cases, male factor was of unknown
      origin or was associated with vasectomy reversal in men with known prior
      fertility. The findings indicate that an impaired capacity to promote the growth
      of microtubule arrays from the sperm centrosome may preclude pronuclear
      opposition required for syngamy. Centrosome dysfunction may contribute to the
      developmental arrest of human embryos at the pronucleate stage and consequently
      may represent a new class of sperm defects associated with early human
      developmental failure.

PMID- 9238704
TI  - Structure-function relationship of recombinant follicle stimulating hormone
      (Puregon).
AB  - After separation by means of preparative isoelectrofocusing, the isohormones of a
      Chinese hamster ovary (CHO)-derived recombinant follicle stimulating hormone
      (rFSH, Puregon) were characterized with respect to structural and functional
      features. A carbohydrate analysis revealed that rFSH isohormones with a low
      isoelectric point (pl) have a high sialic acid/galactose ratio and are rich in
      tri- and tetra-antennary N-linked carbohydrate chains in comparison with the high
      pl isohormones. The relative basic isohormones exhibit receptor binding activity
      and intrinsic bioactivity 2-3-fold higher than the relative acidic isohormones.
      However, due to their lower clearance rate these acidic isohormones displayed a
      20-fold higher in-vivo bioactivity in the rat. A comparison of the isohormone
      profile of rFSH and urinary FSH (Metrodin) revealed that rFSH contains about 2
      fold more basic isohormones with pl > or = 4.7 and 2-fold less acidic isohormones
      with pl < 4.1. In-vitro studies showed that the receptor binding affinity and
      intrinsic bioactivity of both FSH preparations are similar. Also the in-vivo
      efficacy and the pharmacokinetic behaviour of rFSH and urinary FSH in the rat
      were similar, which is not surprising since both preparations were compared in
      terms of in-vivo bioactivity calibrated in the rat Steelman-Pohley assay.
      However, in dogs the bioavailability of rFSH was lower than that of urinary FSH,
      which is in agreement with the higher percentage of relative basic isohormones in
      rFSH. This suggests that the pharmacokinetic behaviour of FSH in rats and dogs is
      different, which is supported by the much longer elimination half-life of rFSH
      and urinary FSH in dogs (27.9 and 30.4 h respectively) compared with rats (11.4
      and 10.4 h respectively) for rFSH and urinary FSH respectively. The observed
      differences in pharmacokinetic behaviour in dogs and rats indicate that the rat
      Steelman-Pohley assay might not be a valid model for the prediction of the FSH
      bioactivity in species other than rat.

PMID- 9238703
TI  - Expression of leukaemia inhibitory factor receptor subunits LIFR beta and gp130
      in human oocytes and preimplantation embryos.
AB  - The expression of both components of the high-affinity leukaemia inhibitory
      factor receptor, LIFR beta and glycoprotein 130 (gp130), was investigated in
      human oocytes and individual in-vitro cultured preimplantation embryos by reverse
      transcription-polymerase chain reaction (RT-PCR). Messenger RNA of both LIFR beta
      and gp130 was detected in as little as 1/30 and 1/12 sample equivalents of cDNA
      respectively, in oocytes (n = 4), 4-cell and expanded, blastacyst stage embryos.
      LIFR beta but not gp130 transcripts were detected at the 2-, 8- and 10-cell
      stages, and in cavitating and hatched blastocysts. In order to exclude a simian
      origin of these PCR products resulting from the Vero cell line that was used as a
      feeder during culture to the blastocyst stage, they were digested with
      restriction endonucleases Taql (LIFR beta) or Kpnl (gp130). Their human origin
      was confirmed. The results support an earlier finding of LIFR beta mRNA
      expression in human blastocysts, and extend these results to earlier stages and
      oocytes. This is the first report of LIFR beta and gp130 transcription in human
      oocytes. Taken together these results demonstrate that transcription of LIFR beta
      and gp130 takes place throughout human preimplantation development, and suggest
      that functional LIF receptors might be present at these stages. These results
      further confirm the feasibility of performing mRNA phenotyping of multiple genes
      with RNA derived from a single preimplantation stage embryo.

PMID- 9238705
TI  - Molecular biology and biochemistry of human recombinant follicle stimulating
      hormone (Puregon).
AB  - Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein hormone
      produced in the anterior pituitary gland. The hormone is essential in the
      regulation of reproductive processes, such as follicular development and
      ovulation. It is clinically used for treatment of anovulation and in assisted
      reproduction technologies such as in-vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). Until recently, the only source for
      human FSH has been the urine from post-menopausal women. Such a natural source
      implies limited availability and potential product variability. Thus, we have
      cloned the genes encoding the alpha- and beta-subunits of human FSH and
      transfected these into Chinese hamster ovary (CHO) cells. A CHO-clone was
      isolated capable of secreting intact glycosylated FSH with identical amino acid
      sequences to natural FSH. This cell line was grown in perfusion culture and
      enabled us to isolate highly pure FSH (> 99%). The complexity of the charge
      distribution of human recombinant FSH was demonstrated by Isoelectric focusing.
      The observed microheterogeneity is caused by the large number of carbohydrate
      chain structures which are added to the four potential glycosylation sites in the
      alpha beta-dimer. Furthermore, the carbohydrates show a variation in their degree
      of sialylation which reflects the different pl values of the individual
      isohormones. Despite the complexity of post-translational modification, the
      isoform distribution of recombinant FSH produced in a CHO-cell line and grown in
      perfusion culture is surprisingly similar to that observed with pituitary FSH and
      urinary FSH. In conclusion, we have shown that FSH-gene transfected CHO-cells are
      capable of stable serum-free production of recombinant FSH. A process has been
      developed which assures the consistent and reproducible production of highly
      purified recombinant FSH.

PMID- 9238706
TI  - Mechanism of calcium oscillations in human oocytes: a two-store model.

PMID- 9238707
TI  - Regulation of calcium spiking in mammalian oocytes through a combination of
      inositol trisphosphate-dependent entry and release.

PMID- 9238708
TI  - How and why spermatozoa cause calcium oscillations in mammalian oocytes.

PMID- 9238709
TI  - Expression of Ad4-BP/cytochrome P450 side chain cleavage enzyme and induction of
      cell death in long-term cultures of human granulosa cells.
AB  - Freshly isolated granulosa cells obtained from women undergoing in-vitro
      fertilization (IVF) become refractory to further gonadotrophin stimulation in
      culture due to their previous hormonal treatment. However, when precultured for 7
      days in gonadotrophin-free medium they regain their response to both human
      chorionic gonadotrophin (HCG) and follicle stimulating hormone (FSH) with a 10
      fold and 5-fold increase in progesterone production respectively, within an
      additional 7 days of culture. Forskolin, a direct activator of adenylate cyclase,
      increased progesterone levels 12-fold compared with non-stimulated cultures.
      Oestradiol formation was also significantly elevated (P < 0.005) following 48 h
      stimulation with luteinizing hormone (LH), FSH or forskolin. Intracellular cAMP
      levels rose 1.5-fold, 10-fold and 15-fold after 1 h of FSH, HCG or forskolin
      treatment. Expression of both cytochrome P450 side chain cleavage enzyme (SCC)
      and the steroidogenic transcription factor SF1/Ad4BP could be demonstrated by
      Western blotting. However, elevation of P450 SCC alone was evident following FSH
      and HCG stimulation. In the presence of serum, the ultrastructure of these
      cultured cells displayed numerous lipid droplets and well-developed mitochondria,
      characteristic of highly steroidogenic cells. The proportion of apoptotic nuclei
      in these cultures was < 30%. Removal of the serum increased apoptotic incidence
      to 40%, whereas addition of FSH prevented cell death significantly (P < 0.01).
      HCG and forskolin increased apoptosis to approximately 50%, while treatment with
      8Br-cAMP led to 80% cell death. Our data suggest that, after prolonged culture,
      human granulosa cells can regain cAMP and steroidogenic response to gonadotrophin
      stimulation. Moreover, our experiments indicate that apoptosis and
      steroidogenesis can coexist in the same cell population while the
      interrelationship between these processes can be determined by the intracellular
      levels of cAMP.

PMID- 9238710
TI  - Involvement of protein kinases in platelet activating factor-induced acrosome
      reaction of human spermatozoa.
AB  - The involvement of protein kinases in platelet activating factor (PAF)-induced
      acrosome reaction of human spermatozoa was investigated using specific inhibitors
      of protein kinase A (PKA), protein kinase C (PKC) and protein tyrosine kinase
      (PTK). PAF (10(-9)-10(-11) M) treatment of spermatozoa enhanced the acrosome
      reaction in a dose-dependent manner (32 +/- 4% at 10(-9) M, 28 +/- 4% at 10(-10)
      M and 24 +/- 3% at 10(-11) M respectively). When spermatozoa were preincubated
      with PKA, PKC and PTK inhibitor (KT5720, calphostin C and genistein) for 15 min
      prior to addition of PAF, there was a significantly reduced acrosome reaction
      induced by PAF, but complete inhibition was not observed. On the other hand,
      combined use of three inhibitors completely inhibited PAF-induced acrosome
      reaction to levels of non-treated samples. These results suggest that the
      induction of the acrosome reaction by PAF treatment may involve the activation of
      PKA, PKC and PTK signalling pathways, and that interaction between these pathways
      may regulate complex mechanisms of PAF-induced acrosome reaction.

PMID- 9238711
TI  - Cytokines-adhesion molecules-invasive proteinases. The missing
      paracrine/autocrine link in embryonic implantation?
AB  - How implantation is regulated and brought about remains an enigma. The objective
      of the present review is to propose a hypothetical model based on our actual
      knowledge of the role of cytokines, adhesion molecules and invasive proteinases
      in the adhesion and invasion phases of embryonic implantation. For the purpose of
      clarity we will describe first what is known about the presence of these
      molecules in the endometrium and embryo in animal models and their relevance in
      embryonic implantation. Secondly, since human implantation is unique the presence
      of these factors in the human endometrium and embryo and their possible clinical
      relevance is considered separately. Finally, the link between cytokines, adhesion
      molecules and invasive proteinases as well as their endocrine/paracrine/autocrine
      regulation is put forward as a possible model that could lead us to a better
      understanding of the implantation process in humans.

PMID- 9238712
TI  - Cell surface peptidases in human endometrium.
AB  - Three cell surface peptidases have been shown to be present in the human
      endometrium. Aminopeptidase N and neutral endopeptidase are detected on the
      endometrial stromal cells and decidual cells, while dipeptidyl peptidase IV is
      detected on the endometrial glandular cells and surface epithelium. As these cell
      surface peptidases can degrade a variety of biologically-active peptides
      including cytokines and growth factors, they are considered to be involved in the
      local metabolism of these molecules. In addition, recent studies have indicated
      that they are involved in local immune responses, cell attachment, and cellular
      maturation/ differentiation of endometrial cells, and suggest an important role
      of these endometrial cell surface peptidases in implantation processes.

PMID- 9238713
TI  - Nuclear factor-kappa-B/steroid hormone receptor interactions as a functional
      basis of anti-inflammatory action of steroids in reproductive organs.
AB  - The transcription factor, nuclear factor-kappa-B (NF-kappa B), can be induced by
      pro-inflammatory cytokines and is important in immunological and inflammatory
      processes because it directs transcription of chemoattractants, cytokines
      (including the NF-kappa B-inducing cytokines themselves), cytokine receptors and
      cell adhesion molecules. We and others have recently found that NF-kappa B and
      the glucocorticoid or progesterone receptor mutually suppress each other's
      activity. Because of its central role in signal transduction in immunological and
      inflammatory responses, inhibition of NF-kappa B activity by glucocorticoids and
      progestins provides an explanation for the anti-inflammatory and
      immunosuppressive activity of these molecules. Since suppression of inflammatory
      processes leading to menstruation and parturition are among the key functions of
      progesterone, the repression of NF-kappa B activity by the progesterone receptor
      may prove to be essential in the regulation of these processes. Recent data show
      that it may be possible to select progesterone receptor ligands that are more
      efficient suppressors of NF-kappa B activity, and which may therefore be more
      effective in modulating these major reproductive processes.

PMID- 9238714
TI  - Localization of endothelin receptors in human uterus throughout the menstrual
      cycle.
AB  - Quantitative autoradiography employing the ETA selective ligand [125I]PD 151242
      and the ETB selective ligand [125I]BQ3020 was used to assess the localization of
      ETA and ETB receptors in human uterus throughout the menstrual cycle. ETA and ETB
      receptors were present in endometrium and myometrium across the menstrual cycle.
      In myometrium, neither ETA nor ETB receptor density showed any detectable change
      across the menstrual cycle. ETA receptors were expressed in stroma throughout the
      endometrium and showed an increase in density in proliferative endometrium
      compared with secretory and menstrual endometrium. Endometrial ETB receptors were
      expressed at low density in the proliferative phase. In the early secretory phase
      there was an increase in ETB receptor density in the glandular epithelium of the
      basal region of the endometrium but not in functional endometrium. In the late
      secretory phase ETB receptor expression was increased in glandular epithelium
      throughout the endometrium. The highest density of ETB receptors was seen in
      menstrual endometrium, where they were present in stromal as well as epithelial
      cells. These results suggest that ovarian steroid hormones may play a role in the
      control of expression of ETA and ETB receptors in endometrial stromal and
      epithelial cells respectively.

PMID- 9238715
TI  - The distribution of alpha- and gamma-tubulin in fresh and aged human and mouse
      oocytes exposed to cryoprotectant.
AB  - The distribution of alpha- and gamma-tubulin in human and mouse oocytes has been
      investigated immunocytochemically. Comparisons have been made between freshly
      recovered and aged oocytes (both human and mouse), and also between human oocytes
      before and after exposure to cryoprotectant. Control fresh human oocytes had
      compact anastral spindles oriented orthogonal to the oolemma, with the pole
      adjacent to the oolemma being smaller than that directed towards the centre of
      the oocyte. Each pole was associated with a ring of particulate gamma-tubulin
      staining that extended a short distance into the body of the spindle. No alpha-
      and gamma-tubulin staining was found elsewhere in the ooplasm. Human oocytes
      which had failed to fertilize after an 18 h incubation with spermatozoa and had
      spent a further 6-8 h in culture showed an increased incidence of spindle
      abnormalities and of the proliferation of ooplasmic microtubules, which became
      more pronounced with age post-ovulation. The gamma-tubulin staining pattern of
      these aged human oocytes revealed greater staining over the whole of the spindle
      than in fresh oocytes. Examination of mouse oocytes aged in vitro or in vivo
      showed similar evidence of microtubule proliferation and disorganization, and the
      gamma-tubulin staining pattern was a sensitive indicator of ageing. The spindles
      of most fresh human oocytes exposed to 1.5 M dimethyl sulphoxide (DMSO) at 4
      degrees C differed from controls in being slightly reduced in size or in having
      more pointed spindle poles with smaller diameters, both indications that some
      dismantling of the microtubules had occurred. The distribution of gamma-tubulin
      in these oocytes extended over more of the spindle. Restoration of DMSO-exposed
      oocytes to control medium at 37 degrees C for an extended period restored spindle
      structure to a state closely resembling that in controls. However, recovery of an
      exclusively polar gamma-tubulin staining did not occur. In both controls and DMSO
      exposed human oocytes, chromosomes were arranged on the metaphase equatorial
      plate. In contrast, exposure of oocytes to 4 degrees C in the absence of DMSO
      caused dismantling of the spindle. It is concluded that (i) changes in
      microtubule organization with ageing of oocytes makes them unsuitable for use
      therapeutically after re-insemination or intracytoplasmic sperm injection, (ii)
      conditions of cryoprotectant addition previously found optimal for the
      stabilization of the spindle in the mouse oocyte also appear to be effective in
      stabilizing the spindle of the human oocyte, and (iii) the distribution of gamma
      tubulin in relation to the spindle of the human oocyte appears to be sensitive to
      age and conditions.

PMID- 9238716
TI  - Expression of steroidogenic factor-1 (SF-1) mRNA and protein in the human
      placenta.
AB  - Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein (Ad4BP),
      is a recently-described transcription factor, which has been shown to be
      important for the differentiation of steroidogenic tissues. In addition, SF-1 has
      been implicated in regulating the glycoprotein hormone alpha-subunit gene in a
      pituitary gonadotroph cell line. Considering that the human placenta produces
      both steroids and human chorionic gonadotrophin (HCG), we studied the expression
      of SF-1 in this tissue. Human first trimester and term placentas were collected
      at the time of therapeutic abortion and birth respectively. Messenger RNA was
      extracted, reverse transcribed, and used for polymerase chain reaction (PCR)
      amplification with primers specific for the human SF-1 cDNA sequence. A band of
      the expected size was obtained from both first and third trimester samples,
      indicating that SF-1 expression in the human placenta starts early in pregnancy
      and is maintained until birth. In addition to normal placental samples, JEG3 and
      JAR choriocarcinoma cells were also analysed and found to express SF-1 mRNA. The
      identity of the amplified products was confirmed by diagnostic restriction digest
      and Southern hybridization. SF-1 protein was localized mainly to the nuclei of
      the cyto- and syncytiotrophoblast and to some mesenchymal villous nuclei by
      immunocytochemistry using a specific antibody. We conclude that SF-1 is expressed
      in human first trimester and term placenta, where it could be implicated in the
      regulation of HCG production, in steroidogenesis, or both.

PMID- 9238717
TI  - Placental mRNA expression of alpha and beta human chorionic gonadotrophin in
      early trisomy 18 pregnancies.
AB  - The placental expression of human chorionic gonadotrophin (HCG) I- and beta
      subunits was investigated in eight pregnancies presenting with trisomy 18 and in
      30 normal pregnancies at 11-15 weeks gestation. In the control group, the median
      densitometric scores of placental beta-HCG and I-HCG mRNA were 1.23 and 1.74
      respectively. In the trisomy 18 group the median beta-HCG mRNA was significantly
      lower (0.16, Z = 2.29, P < 0.05) but alpha-HCG [0.60, Z = 1.75, P = 0.08) was not
      significantly different from normal. These findings suggest that in trisomy 18
      the decrease in maternal serum concentration of HCG subunits results from an
      impairment in the transcription of the corresponding gene which affects the beta
      subunit to a greater extent than the I subunit.

PMID- 9238718
TI  - To tip or not to tip?

PMID- 9238719
TI  - Reliability of lower extremity girth measurements after anterior cruciate
      ligament reconstruction.
AB  - The purpose of this study was to determine the intra- and inter-rater reliability
      of lower extremity girth measurements in patients recovering from anterior
      cruciate ligament (ACL) reconstructive surgery. Nine subjects, within several
      months of their surgery, volunteered. Circumferential measurements were taken of
      the involved and uninvolved legs at the following locations: 15 cm inferior to
      the joint line; 5, 10 and 15 cm superior to the joint line; at the joint line;
      and at mid-thigh. All subjects were supine with the knee in extension whilst a
      specially designed device, formulated to make circumferential measurements at
      locations around the knee, was applied to the extremity. Three physical
      therapists each repeated all measurements on two occasions, in random order,
      during the same test session. Intra-tester intraclass correlation (ICCs)
      calculated showed high coefficients (0.82-1.0) for both the involved and
      uninvolved sides for all locations of the measurement. Inter-tester ICCs ranged
      from 0.72 to 0.97. The measurements established sufficiently high reliability to
      justify their use both within and between examiners for subjects recovering from
      surgery of the ACL.

PMID- 9238720
TI  - Disability and health: perceptions of a sample of elderly people.
AB  - The background to this work was the expected increase in the proportion of
      elderly people in the population, giving rise to a greater demand for services at
      a time of scarcity of healthcare resources. The aims of the study were to
      investigate disability and health in a sample of elderly people living at home in
      the community. We wished to obtain detailed information about physical disability
      and health then to explore individual perceptions of health and disability and,
      finally, to examine relationships between the objective assessments and
      individual, subjective perceptions. The results reported here represent only part
      of the work of a larger study which also investigated the use of health and
      social services in this sample of elderly people. In-depth interviews were
      undertaken with a random stratified population sample of 200 elderly people
      living at home. Analysis of interview data showed that, by use of a
      multidimensional scale of disability, just over one-third of the sample could be
      classified as 'disabled'. The mobility status of the sample was, in general, good
      with only small numbers spending most of their time in a wheelchair. The total
      sample scored highly on activities of daily living, though those classified as
      disabled were significantly less independent. The mean number of reported health
      conditions was less than might have been expected in an elderly population. One
      third of the subjects in the sample showed discrepancies between their own
      assessment of their disability and objective assessments. These discrepancies
      could partly be explained by a combination of individuals' assessment of their
      own abilities and their beliefs about factors influencing disability. Measures of
      disability, or activity associated with daily living, were related to perceptions
      of health, whereas the number of current health problems was not. The factors
      which determined perceptions of health or disability were: walking unaided and
      general levels of activity. Health was perceived in terms of what one could do
      rather than the presence of current diseases or conditions. The results suggested
      that when planning treatment for elderly people, physiotherapists and others
      should consider individual variability in perceptions of disability and health,
      as well as objective assessments. The importance of locomotion in the value
      systems of elderly people emphasises the high profile of physiotherapy in the
      care of elderly people.

PMID- 9238721
TI  - Evaluation of the relationship between laboratory and clinical tests of
      transversus abdominis function.
AB  - A clinical test of the function of the deep abdominal muscles was compared to a
      laboratory electromyographic (EMG) investigation of the contribution of
      transversus abdominis (TrA) to stability of the lumbar spine during limb
      movement. The two different functions of TrA were evaluated in 15 subjects. The
      subject group included six subjects with chronic low back pain and nine subjects
      with no history of low back pain so that the resultant recordings were spread
      over a wide range for each test. The clinical test involved quantification of the
      ability of the subjects to specifically displace the anterior abdominal wall in a
      way consistent with the function of the muscle. This was evaluated by use of a
      device designed to measure pressure reduction as the abdomen lifted off a
      transducer in the prone position. The laboratory test involved determination of
      the onset of contraction of TrA associated with rapid upper limb movement,
      measured using fine-wire EMG electrodes. The parameter evaluated was the latency
      between the contraction of TrA and the prime mover of the limb. Data were
      analysed both as absolute values and as ordinal data of a three-rating scale
      derived from criteria based on current knowledge of the response to both tests.
      No significant correlation was found between the absolute magnitudes of the
      pressure and timing data, however, comparison of the rating scale data indicated
      a significant relationship between the tests and associated high level of
      agreement between the two measures. The results of the study indicate that a
      reduction in the ability to draw in the abdominal wall is related to changes in
      the coordination of TrA, although the magnitude of the changes were not
      correlated. The degree of causality between these co-varying but independent
      manifestations of the function of TrA is uncertain.

PMID- 9238722
TI  - Peripheral cutaneous nerve distribution to the fingers.
AB  - Both sensory distribution charts and the unaffected side, are used as reference
      points in the assessment of cutaneous innervation. Sensory nerve conduction
      studies, in particular, often use comparison between sides. However, remarkable
      differences can be found between various sensory innervation maps, and no
      evidence was found in the literature for the assumption that the pattern of
      cutaneous sensory distribution of the peripheral nerves between the left and
      right limbs is symmetrical. The purpose of this study was to investigate
      variations in the sensory innervation of the fingers by means of a
      neurophysiological method, and to compare the results for the left and right
      hands. The subjects of this study were 31 young women. Percutaneous peripheral
      nerve stimulation was performed on the four nerve branches providing sensory
      innervation to the fingers, and action potentials were sought from the fingers by
      use of annular surface electrodes. Variations in the cutaneous innervation of the
      fingers between individuals often occurred and were found more frequently on the
      dorsal than the palmar aspect. The distribution of sensory innervation may even
      differ markedly between hands in the same individual. The cutaneous innervation
      of all peripheral nerves supplying the fingers may differ from the innervation
      patterns described in the various distribution charts. Prudence is called for
      when applying sensory distribution charts as absolute references for the
      assessment of cutaneous sensation in patients. Caution should also be applied
      when comparing one hand with the other when assessing the cutaneous innervation
      of the fingers.

PMID- 9238723
TI  - Evaluation of the reliability of reflective marker placements.
AB  - This study determined the reliability of recording knee angle coordinates in the
      sagittal plane during erect stance by use of skin reflective markers. To this
      end, 32 healthy male and female subjects participated in three standardised test
      sessions of 1 hour duration spaced at 1- and 4-week intervals. At each session,
      markers were placed on three bony landmarks of the leg and their coordinates were
      photographed with the leg in extension and semi-flexion. The resultant knee
      angles, calculated from lines drawn on the photographs marking the coordinate
      sites, were subjected to separate repeated measures analysis of variance
      statistical procedures. The results showed that both sets of measurements could
      be carried out reliably when repeated within a single test session (R = 0.87).
      However, when repeated over time, neither measurement reached the criterion for
      acceptable reliability (set at R > or = 0.80). The magnitude of the method error
      was also higher between test sessions for both angles than it was for tests
      repeated within the sessions. These data suggest that whereas knee coordinates
      recorded on a single day can be reproduced reliably, they may be less useful for
      evaluating knee angle changes over time.

PMID- 9238724
TI  - Evidence based medicine--implications for physiotherapy?

PMID- 9238725
TI  - Physiotherapy after stroke: more is better?
AB  - Physiotherapy is an established component of stroke rehabilitation but
      uncertainties remain about the most appropriate intensity of therapy input. We
      conducted a systematic review of the randomised trials of physiotherapy after
      stroke where qualitatively similar therapy regimens were provided at different
      levels of intensity. A heterogeneous group of seven randomised trials (597
      patients) was identified. Dichotomous outcomes (death or the combined poor
      outcome of death or deterioration) were analysed by use of the odds ratio and 95%
      confidence interval. Patients subjected to more intensive physiotherapy input
      showed a non-significant reduction in case fatality (odds ratio 0.60; 95% CI 0.33
      1.09) and a significant reduction (OR 0.54; 95% CI 0.34-0.85; p < 0.01) in the
      combined poor outcome of death or deterioration by the end of follow-up. Two
      statistical techniques were used to identify patterns within the continuous data.
      Firstly, impairment and disability scores were converted to a standardised
      measure of 0-100 and the weighted mean difference (WMD) between the scores in the
      intensive and conventional physiotherapy groups were then calculated. Modest
      improvements were observed in both the impairment (WMD+5; 95% CI-1-11) and
      disability scores (WMD+5; 95% CI 0-10) recorded at the initial review (median 3
      months post-stroke), but not at the final review (median 1 year post-stroke).
      Secondly, Fisher's inverse chi-squared test was used to combine the p values from
      individual trials; this confirmed the above findings (p < 0.05 at initial review;
      p > 0.05 at final review). More intensive physiotherapy input was associated with
      a reduction in the combined poor outcome of death or deterioration and may
      enhance the rate of recovery. These observations warrant further investigation.

PMID- 9238726
TI  - Physiotherapy in knee osteoarthrosis: effect on pain and walking.
AB  - Patients with knee osteoarthrosis are often referred for physiotherapy and many
      different types of treatment are given. The value of many of these treatments has
      been questioned. This study was intended to evaluate the effect of commonly used
      physiotherapy treatments in a training programme on patients with medial knee
      osteoarthrosis, scheduled for surgery. The results from this study also provide
      useful data for further evaluation of different physiotherapy treatments to this
      patient group. Thirty-four patients were randomised to physiotherapy three times
      a week for 5 weeks and the other 34 received no treatment. The training programme
      is described in detail. The patients were evaluated by clinical examination, step
      test, gait analysis and isokinetic measurements of thigh muscle strength before
      and after treatment. The patients in the treatment group experienced a feeling of
      overall improvement in the knee and the ability to descend steps improved when
      compared to the control group. There were no significant differences in gait,
      range of motion or isokinetic measurements of muscle strength between the groups.
      We conclude that physiotherapy as given here made our patients feel better and
      their ability to descend stairs improved. These improvements are beneficial to
      the patients and support the positive effects of exercises and activity. Whilst
      the objective improvements were small, suggesting that this treatment may not be
      justified, patients in the treatment group believed that they were improved.

PMID- 9238727
TI  - Assessment of motor function in people with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic progressive disease of the central nervous
      system (CNS) which predominantly affects young adults. In order to provide
      physiotherapy appropriate to the needs of individuals with MS, it is necessary to
      assess and evaluate the nature and degree of motor and functional deficits. The
      aim of this research was to develop a physiotherapy assessment which would
      consistently and objectively evaluate motor function in people with MS. The Motor
      Club Assessment (MCA), originally developed for use in stroke patients, was
      identified as exhibiting several features which were consonant with the required
      criteria. It was therefore modified for use in MS. The Amended MCA (AMCA) was
      tested for inter-rater agreement, which was found to be good for the lower limb
      motor section (weighted kappa = 0.80), the upper limb motor section (weighted
      kappa = 0.90), and the functional activities section (weighted kappa = 0.92). The
      internal consistency was high for the lower limb section (alpha = 0.97) and the
      functional activities section (alpha = 0.92), but could not be determined for the
      upper limb section due to a clear ceiling effect. The study demonstrated that the
      AMCA is a valid tool for assessment use by physiotherapists in MS patients, and
      that it has an acceptable level of reliability when used in a clinic setting by
      physiotherapists suitably experienced in the treatment of neurological patients.

PMID- 9238728
TI  - The reliability of measuring quadriceps cross-sectional area with compound B
      ultrasound scanning.
AB  - Many therapists use thigh circumference as a measure of quadriceps size to
      evaluate the effect of an injury or effectiveness of an intervention. However,
      this technique has been shown to be unreliable, thus more accurate methods of
      measuring muscle size are required. The purpose of this study was to investigate
      the validity and reliability of measuring quadriceps cross-sectional area (CSA)
      with static compound B ultrasound scanning at the level of the mid-thigh.
      Repeated measures of known linear distances and CSAs were made with a planimetry
      device. Both face and criterion validity were demonstrated indicating that the
      device is reliable when measuring CSAs. A single rater located quadriceps muscle
      borders and measured CSAs on a series of ultrasound scans. A mean coefficient of
      variation (%CV = 1.7) was observed, signifying high intra-rater reliability. Two
      raters performed six scans on each of 15 subjects. Initial observation of these
      results suggest that the measurement of quadriceps CSA with compound B ultrasound
      scanning is reliable, mean %CVs = 2.8 and 1.9 for the two raters and 2.4 when
      their results were combined. When raters performed scans on 18 subjects on two
      occasions on the same day intra-class correlation coefficients (ICC) were high,
      0.991 and 0.980 for raters A and B, respectively. Paired Student's t-tests
      revealed a significant difference (p < 0.05) for Rater B between CSAs measured
      for initial and relocated scans. However, this difference was calculated as 1.4
      2.9% and was not of clinical importance. A significant difference (p < 0.05) was
      observed between measurements of CSAs made by both raters on the same subject. A
      calibration factor was calculated for transforming the measurements of Rater B,
      the use of which gave comparable values. ICCs using a fixed model for inter-rater
      reliability were 0.963 and 0.974 for actual and transformed values, respectively.
      This study observed differences between measures obtained by different raters and
      recommends that the calculation and employment of a calibration factor may be
      useful when comparing sequential measures made by different raters.

PMID- 9238729
TI  - Further evidence of impaired position sense in knee osteoarthritis.
AB  - The knee joint position sense of a control group of healthy women was compared
      with that of women diagnosed as having severe osteoarthritis (OA) of the knee.
      Movements monitored were multi-joint when weightbearing on one leg. All subjects
      completed two angle rematching tests on two separate test occasions, and the
      criterion and reproduction angles which lay in the range of 15-45 degrees knee
      flexion were recorded photographically on each occasion. The results showed that
      the OA group performed the rematching tests with less accuracy than the controls
      (p < 0.05). Additionally, the OA group displayed significantly higher average
      flexion error magnitudes than the controls. These results suggest that joint
      position sense is less accurate and may be systematically distorted during multi
      joint movements of the affected legs of a high proportion of women with severe
      knee OA. They further suggest that to improve their functional performance,
      patients with knee OA probably require a carefully constructed sensorimotor
      rehabilitation programme in which pain, effusion and fatigue are minimised.

PMID- 9238730
TI  - A little bit of toxin does you good?

PMID- 9238731
TI  - Measurements of scapular position and rotation: a reliability study.
AB  - Smooth motion of the scapula and humerus with respect to the thorax is essential
      for shoulder function and abnormalities may indicate clinical entities. Recent
      studies have made an attempt to devise simple, practical means of quantifying
      scapular position. The aim of this study was to examine the intra-tester and
      inter-tester reliability of two methods and to determine if significant
      differences existed between the dominant versus non-dominant extremity. Seventeen
      healthy volunteers (4 M; 13 F) were examined by two testers. The tape
      measurements consisted of the classic methods of Kibler and DiVeta in three
      sitting postures, expanded by the measurement of the linear distance from the
      medial border to the thoracic mid-line, and the scapular size measure. The SAS
      software package was used for data analysis. The Intraclass Correlation
      Coefficient (ICC) intra-tester reliability ranged between 0.96-0.8 for both
      methods without significant differences, whereas the ICC for inter-tester
      reliability ranged between 0.42-0.9 with higher values (moderate and good) for
      the Kibler technique. In the additional tests high values were also obtained for
      ICC intra-tester, except for the measurements of the linear distance of the
      medial border of the scapula to the thoracic mid-line and the distance of the
      inferior process of the acromion to the third vertebra, both in 90 degrees
      abduction and internal rotation. The ICC for inter-tester was only acceptable for
      the DiVeta measurement on 45 degrees abduction. Significant differences were
      noted between both testers on the following measures: Kibler in 45 degrees
      abduction, DiVeta in 45 degrees abduction and 90 degrees abduction and the
      scapular size measure. The comparison of dominant versus non-dominant extremity
      revealed larger but not significantly different means for the dominant extremity
      in the classic methods. Significant differences occurred for Tester 1 in the
      measurement of the distance of the medial border to the thoracic mid-line and
      Tester 2 in DiVita in 45 degrees abduction. The SEM values never exceeded 1 cm.
      We believe that the Kibler technique holds promise for further studies, has the
      advantage of measuring in three positions and with some familiarisation can be
      reliable. Further research is necessary in patients with pathological conditions.

PMID- 9238732
TI  - Physical therapists' perceptions of family involvement in the rehabilitation
      process.
AB  - The purpose of this qualitative study was to describe how physical therapists
      working in rehabilitation settings involved families in the patient's
      rehabilitation program and what factors facilitated or impeded this involvement.
      Forty physical therapists practicing in the eastern United States were
      individually interviewed on their involvement of families in a patient's
      rehabilitation. The interview data were transcribed, coded, and analyzed for main
      themes. Family involvement was found to be a significant aspect of a patient's
      rehabilitation. Factors pertaining to the family, the patient, the healthcare
      organization and the physical therapist were identified. Factors, such as the
      family's knowledge, attitudes and skills of the family, their relationship with
      the patient prior to the injury or disability, the availability and opportunity
      of family members to be involved, and their physical capabilities, all influenced
      the degree to which the family participated. Therapists also perceived the
      cognitive status of the patient as a factor which dictated the proper amount of
      family participation. The healthcare organization was an important factor which
      needed to encourage and support the family participation. With decreased lengths
      of stay there is less time for families to be independent in caring for their
      loved one. The organization of the department could be instrumental in this by
      providing multiple formal and informal avenues for family training, such as
      support groups, home visits, 'open door' policy visiting hours, and scheduling
      changes. Finally, the physical therapists might have been the single most
      significant factor in facilitating family involvement. It was important for them
      to establish open and honest communication and be pro-activists for their
      patients and their families. The findings were consistent with the existing
      literature base in relation to the patient and family. Additional findings
      present physical therapists and healthcare organizations with suggestions for
      improving family education.

PMID- 9238733
TI  - Responsiveness and reliability of a pediatric strategy score for balance.
AB  - Various motor patterns or 'strategies' can be used to maintain balance. The
      purpose of this study was to determine the responsiveness of a pediatric strategy
      score (PED-SS) compared to a standard strategy score (SS) as a measure of age
      related changes in the force patterns used to maintain stance. Eighty-one healthy
      children between 3-6 years of age were tested during stance on a force platform
      while facing a visual surround. The platform, visual surround (or both) moved
      simultaneously with the child's body sway. Four sensory conditions that altered
      visual and somatosensory (support surface) inputs were presented. The PED-SS was
      found to be more responsive to age-related changes in balance behavior compared
      to the SS. The oldest children (aged 5 and 6 years) showed the greatest ability
      to utilize horizontal A/P shear force to maintain stance and this finding was
      reflected only in the PED-SS. The implications of evaluating force strategy as
      one component of balance in healthy children is discussed with respect to the
      early developmental assessment of vestibular and developmental coordination
      disorders.

PMID- 9238734
TI  - Concentric and eccentric force-velocity relationships during electrically induced
      submaximal contractions.
AB  - The purpose of this investigation was to examine the force-velocity relationship
      during electrically induced, submaximal concentric and eccentric contractions of
      the quadriceps femoris muscle. Thirty female subjects with no history of knee
      pathology participated in the study. Force was measured on an isokinetic
      dynamometer and the quadriceps femoris muscle was electrically stimulated by use
      of a medium frequency current generator. Subjects were stimulated at 30% of their
      maximum voluntary isometric force. Four velocities were tested (30 degrees, 90
      degrees, 120 degrees and 180 degrees/sec) during both concentric and eccentric
      contractions. The relationship between force and velocity was examined with an
      analysis of covariance. The regression model describing the force-velocity
      relationship for concentric contractions was significant (p < 0.0001) with an R2
      of 0.96 and a slope of -0.76 (p < 0.0001). The regression model describing the
      force-velocity relationship for eccentric contractions was significant (p <
      0.0001) with an R2 of 0.91 and a slope of 0.4 (p < 0.0001). The relationship
      between force and velocity during electrically induced, submaximal concentric and
      eccentric contractions were similar to in vitro studies that have examined this
      relationship during shortening and lengthening contractions.

PMID- 9238735
TI  - The bases of practice--neurological physiotherapy.

PMID- 9238736
TI  - Rigorous objectivity and clinical experience.

PMID- 9238737
TI  - Belief and believe: seeking scientific truths that underlie the art of
      physiotherapy.

PMID- 9238738
TI  - AFOs and KFOs and surgery in cerebral palsy--what to use when?

PMID- 9238739
TI  - The use and interpretation of the Friedman test in the analysis of ordinal-scale
      data in repeated measures designs.
AB  - The purpose of this paper is to review the use and interpretation of the Friedman
      two-way analysis of variance by ranks test for ordinal-level data in repeated
      measurement designs. Physical therapists frequently make three or more repeated
      measurements of the same individual to compare different treatments, or to assess
      the effect of a single treatment over time. When the measurements are ordinal
      scaled, such as some ratings of functional status and muscle strength,
      statistical significance may be determined by the Friedman test. We illustrate
      the use of the Friedman test and a post hoc multiple comparison test with data
      from 27 subjects whose performance on a lifting task was rated on three occasions
      by use of an ordinal scale. We discuss the interpretation of ordinal-level data
      and recommend that therapists understand the limitations a measurement scale
      imposes on the inferences that can be made from these tests.

PMID- 9238741
TI  - The job satisfaction of physical therapists.
AB  - Ten statements were created for the purpose of measuring job satisfaction in the
      practise of physiotherapy. The subjects consisted of 96 of the 106 (90%) of the
      physical therapists licensed with the Texas State Board of Physical Therapy
      Examiners, and listed as residing in El Paso, Texas, USA. To indicate their job
      satisfaction, subjects indicated on a seven-point scale their level of agreement
      or disagreement with each statement. They then indicated on a different seven
      point scale how important they thought each statement was to their job
      satisfaction. The results indicated that subjects thought that their jobs were
      challenging in a positive sense; enabled them to use their abilities; and were
      interesting. They also thought that they had sufficient independence in decision
      making; were learning and improving in their work; and were given significant
      autonomy. The most dissatisfying aspect of their work was the amount of
      paperwork. In addition, the results suggest that some subjects may feel
      overworked, and think their jobs may be too physically demanding and mentally
      stressful. The subjects felt that all the statements had validity and measured
      important aspects of job satisfaction in physical therapy.

PMID- 9238740
TI  - Changes in voluntary motor control induced by intrathecal baclofen in patients
      with spasticity of different etiology.
AB  - We studied the effects of intrathecal baclofen upon voluntary movements. Eleven
      patients with spasticity of different etiology and one patient with idiopathic
      dystonia were studied. Six patients participated in a double-blind trial.
      Kinematic/dynamic and electromyographic (EMG) patterns were recorded during
      attempts at single-joint elbow or ankle voluntary movements and isometric
      contractions. Reflex responses were also recorded. Baclofen suppressed spastic
      signs in 10 patients: it eliminated clonus and decreased the co-contraction of
      antagonist and distant muscle groups. Baclofen could induce weakness,
      particularly in patients with cerebral palsy (CP). Patients with hemi-syndromes
      did not notice any effects of baclofen in their 'unaffected' limbs. Intrathecal
      baclofen could improve voluntary movements in some patients with spasticity
      resulting in better walking and usage of arms. We hypothesize that spasticity
      induces an adaptive reaction at a segmental level that includes an increase in
      the number and/or affinity of GABA-sensitive receptors.

PMID- 9238742
TI  - The exercise capacity of three socio-economic groups of elderly hypertensive
      patients.
AB  - A third of all persons over the age of 65 suffer from hypertension. The incidence
      in South African blacks is particularly high. Exercise, although effective in
      lowering blood pressure, has not gained acceptance for its antihypertensive
      benefits. It would certainly be an inexpensive management option in community
      based clinics in South Africa. In this paper, the exercise profiles of a group of
      elderly hypertensive patients are examined in three different socio-economic
      settings: a tertiary care hospital (Group 1); an urban community-based clinic
      (Group 2); and a rural clinic (Group 3). All the patients completed the six
      minute walking test and the Duke Activity Status Index (Hlarky et al., 1984). All
      test values were expressed as means and standard deviations. A p value of < 0.05
      was considered significant. Both resting and exercise pulse rates were higher at
      the urban clinic (p = 0.019). The blood pressure (BP) was higher in the urban
      clinic, but not significant so. The mean arterial pressure (MAP) of all three
      groups was high (115 mm HG). The distance covered in the six-minute walking test
      was surprisingly low at the urban and the rural clinic. Overall, in all three
      settings patients' hypertension was not well-controlled. The patients were not
      fit when compared to their age-predicted metabolic equivalent (MET) values. This
      lack of fitness may indicate that exercise programmes could be of value.

PMID- 9238743
TI  - A discussion paper on the bases of practice in neurological physiotherapy: a
      response.

PMID- 9238744
TI  - Hypotonic abdominal muscle in stroke patients.

PMID- 9238745
TI  - Research and the patient.

PMID- 9238746
TI  - Solving the problem of contractures--throw out the recipe book?

PMID- 9238747
TI  - Why exercise?: a preliminary investigation of an exercise motivation index among
      individuals with rheumatic conditions and healthy individuals.
AB  - The study was undertaken to investigate the test-retest stability and the
      criterion-related validity of a modified Swedish version of an exercise
      motivation index (EMI), and its use with individuals with rheumatic conditions,
      and with healthy individuals who exercised regularly. The EMI consists of 23
      statements divided into three sub-scores for physical, psychological and social
      motivation. Ninety-five individuals with rheumatic conditions (mean age 60 years,
      mean symptom duration 15 years, 79% female) and 131 healthy individuals (mean age
      52 years, 76% female), all attending exercise classes at least once a week,
      filled out the EMI. Sub-samples also filled out three visual analogue scales
      designed to measure physical, psychological and social exercise motivation, and
      filled out the EMI a second time one week later. The results indicated that
      psychological and physical exercise motivation was equally important in both
      samples. Social motivation was less important in both samples, but more
      pronounced in the rheumatic sample and among older individuals. In the rheumatic
      sample, physical motivation was more important among women and psychological
      motivation was more important among younger individuals. Test-retest stability
      for the EMI was satisfactory in both samples, while criterion-related validity
      was poor. The results of our preliminary investigation of the EMI suggest that
      the survey of physical, psychological and social motivation for exercise seems
      meaningful. Further work on the validity of the EMI is needed.

PMID- 9238748
TI  - Physiotherapists' use of evidence based practice: a cross-national study.
AB  - This study investigated clinical physiotherapists' reasons for their use of
      treatment techniques, with a particular focus on their utilisation of journal
      review and research literature. A questionnaire was completed by 180
      physiotherapists in England and 141 physiotherapists in Australia. Despite the
      greater prevalence of pre-registration degree respondents in Australia, there
      were no differences between the two national groups in their reasons given for
      choice of treatment techniques. The basis of over 90% of each groups choice of
      techniques reflected what was taught during their initial training. Experience of
      treatment effects on prior patients, and information gained in practice-related
      courses, were also primary reasons. Research literature ranked least in
      importance as a basis for choosing techniques, and review articles fared little
      better. The results indicated that these physiotherapists relied mainly on
      information gained from formal pre- and post-registration courses. By
      implication, the most obvious means of influencing physiotherapists' attitudes to
      research utilisation lies with those responsible for physiotherapy education.

PMID- 9238749
TI  - A revised group exercise program for osteoarthritis of the knee.
AB  - The purpose of this study was to determine the effectiveness of a group exercise
      program for subjects with osteoarthritis of the knee referred for physiotherapy
      in terms of pain, physical function and gait. This study was initiated after an
      initial group exercise program at this centre failed to demonstrate significant
      changes in pain, physical function or gait. The study was based on repeated
      measures with a two month follow up, carried out in the outpatients department of
      a large public hospital. Pain levels in various functional situations were
      assessed on visual analogue scales, physical function with the Stanford Health
      Assessment Questionnaire, and quantitative gait variables at a normal and a fast
      self-selected speed with an electric foot switch walkway. On completion of the
      program (n = 40) more than 90% of the pain and physical function scores
      demonstrated significant improvements without increases in medication, use of
      walking aids or fatigue. The gait variables of velocity, cadence and stride
      length at both self-selected speeds demonstrated significant increases at this
      assessment without deterioration of gait symmetry. All improvements were
      maintained at the two month follow up assessments. This study suggests that a
      clinically realistic group exercise program supplemented with a home program can
      reduce pain, increase physical function and objective gait measures in subjects
      with osteoarthritis of the knee.

PMID- 9238750
TI  - A weight bearing method for determining forefoot posting for orthotic
      fabrication.
AB  - Orthotic prescription for forefoot posting is commonly based upon measures of the
      forefoot performed on a non-weightbearing foot. However, the relationship of
      measures of the unloaded foot to determine orthotic prescription for compensatory
      forefoot function during gait is still in question. Another approach to determine
      orthotic prescription is to measure the height of forefoot posting necessary to
      prevent excessive pronation of the subtalar joint during weightbearing.
      Therefore, the purpose of this study was to determine the intrarater, interrater
      and day-to-day reliability of forefoot measures during an active, weightbearing
      movement. Thirty-two volunteers, 18 females (mean age 38.9 +/- 15.3 yr) and 18
      males (mean age 44.8 +/- 20.6 yr) participated in the study. Four examiners
      performed repeated forefoot measures on both feet using the weightbearing
      technique during two test sessions separated by a week. Intrarater and interrater
      reliability (ICC (3,1)) ranged from 0.90 to 0.95 and 0.87 to 0.94, respectively.
      Day-to-day reliability (ICC (1,1)) ranged from 0.84 to 0.88 for all measures. We
      conclude that the weightbearing method used in this study to determine forefoot
      posting is reliable. The acceptable reliability of this method justifies the need
      for future investigations of the validity and the clinical efficacy of this
      technique for orthotic prescription.

PMID- 9238751
TI  - Complete excision of the lower trunk and C8 and T1 nerve roots in a patient with
      Pancoast tumor with a resulting fully functional hand.

PMID- 9238752
TI  - Orthoses and surgery.

PMID- 9238753
TI  - Evidence based practice.

PMID- 9238754
TI  - Histamine in cancer immunotherapy.
AB  - A novel strategy for enhancing the efficacy of immunotherapy with interleukin-2
      (IL-2) and interferon-alpha (IFN-alpha) in human neoplasia is presented. IL-2 and
      IFN-alpha are potent activators of the antitumour activity of natural killer (NK)
      cells but only rarely reduce the tumour burden in treated patients. Recent
      studies suggest that a reason why these cytokines are insufficiently effective in
      human cancer is that phagocytes inhibit the tumour-killing activity of NK cells
      at the site of the tumour. Histamine prevents the phagocyte-induced, NK cell
      inhibiting signal; thus, histamine and IL-2 or histamine and IFN-alpha synergize
      to induce NK cell-mediated killing of human tumour cells in vitro. Further,
      treatment of tumour-bearing mice with histamine enhances IL-2- and IFN-alpha
      induced destruction of NK cell-sensitive tumour cells in vivo. More than 50
      patients with neoplastic disease have been treated with histamine, given in
      subcutaneous injections, together with IL-2 or IFN-alpha. The results of two
      pilot trials in metastatic melanoma suggest that the addition of histamine to IL
      2 and IFN-alpha prolongs survival time and induces regression of tumours, such as
      liver melanoma, which are otherwise considered refractory to immunotherapy. The
      results of a trial in acute myelogenous leukaemia (AML) suggest that histamine
      and IL-2 protects AML patients against relapse of leukaemic disease. Histamine is
      well tolerated: for example, AML patients in remission have treated themselves
      with histamine at home without supervision for a total of > 300 weeks with only a
      handful of therapy-related hospital contacts. Controlled trials in melanoma and
      AML are under way to further investigate the putative benefit of histamine in
      neoplastic disease.

PMID- 9238755
TI  - Diagnosis of glomerular haematuria: role of dysmorphic red cell, G1 cell and
      bright-field microscopy.
AB  - Differentiation between glomerular and non-glomerular haematuria by observation
      of the changes in red cell morphology using phase-contrast microscopy is a well
      established technique. However, the method is not widely accepted in clinical
      practice because of controversy regarding the minimum percentage of dysmorphic
      red cells required to diagnose glomerular aetiology, as well as the need for
      specialized microscopes. Recently, a glomerular-specific morphological alteration
      of red cells has been described, which has the form of a doughnut shape with one
      or more blebs and which is termed the "G1" cell. In the present double-blind
      prospective study 250 urine samples were examined without any knowledge of
      diagnosis. Haematuria was detected in 122 cases. The type of haematuria was
      characterized by counting dysmorphic cells and G1 cells separately, in each case
      using a phase-contrast microscope as well as an ordinary bright-field microscope
      with and without staining of urinary sediments. The results were later correlated
      with the confirmed diagnosis. The study showed that the G1 cell is more specific
      than the dysmorphic cell for the diagnosis of glomerular haematuria. Evaluation
      of both dysmorphic red cells and G1 cells can be done using bright-field
      microscopy with 100% specificity and sensitivities of 82 and 100%, respectively.
      It has been concluded that the ordinary bright-field microscope can be used for
      the diagnosis of glomerular haematuria with an efficiency similar to that of a
      phase-contrast microscope.

PMID- 9238756
TI  - Metabolic cobalamin deficiency in patients with low to low-normal plasma
      cobalamins.
AB  - Over a 2-year period, we examined 48 patients with P-cobalamin levels in the
      difficult "grey zone" at the lower reference limit detected by a competitive
      protein binding assay using intrinsic factor as binder. In 21 of 30 patients
      (70%) with low P-cobalamins we could not establish the diagnosis of metabolic
      cobalamin deficiency, but 1 of 18 patients (6%) with low-normal P-cobalamin
      values was confirmed metabolically cobalamin-deficient. Half of these 30 patients
      with low P-cobalamins had neuropsychiatric disorders, but only one-third of the
      latter patients had metabolic cobalamin deficiency. Ten of the remaining 15
      patients (67%) were characterized as non-deficient. In patients with low-normal P
      cobalamin level, we found neuropsychiatric disorders in 5 of the 18 (28%), but
      none of these had metabolic cobalamin deficiency. We conclude that P-cobalamins
      below the reference interval combined with typical neuropsychiatric symptoms or
      findings are not diagnostic of cobalamin deficiency and that further analyses are
      necessary.

PMID- 9238757
TI  - Molecular analysis of porphobilinogen (PBG) deaminase gene mutations in acute
      intermittent porphyria: first study in patients of Slavic origin.
AB  - Acute intermittent porphyria (AIP) is an autosomally dominant inherited metabolic
      disorders caused by decreased activity of porphobilinogen deaminase, the third
      enzyme in the human heme biosynthetic pathway. We report here the first mutations
      in the human porphobilinogen deaminase gene in seven unrelated patients from the
      Czech and Slovak Republics with acute intermittent porphyria. We used denaturing
      gradient gel electrophoresis to screen all 15 exons and exon/intron boundaries of
      the porphobilinogen deaminase gene. Polymerase chain reaction products of
      abnormal migration patterns were subjected to direct sequencing to identify the
      causative mutations. Thus we revealed four novel mutations and three which have
      been previously described. Of the four novel mutations, two were mis-sense (G24S,
      V267M), one was a single base insertion (158insA) that produced a stop codon 12
      codons downstream, and one was a single base substitution in intron 12 (771 + 1)
      resulting in a splicing defect. The three previously detected mutations were mis
      sense mutations (R26C, R26H, G111R). These results suggest a high allelic
      heterogeneity in Czech and Slovak patients.

PMID- 9238758
TI  - Age-specific reference values for serum prostate-specific antigen in a community
      based population of healthy Swedish men.
AB  - To establish normal reference values for prostate-specific antigen (PSA) in a
      Swedish population we investigated 878 healthy men, 56-75 years of age. They were
      randomly selected from a population of 9171 males in this group. Cancer of the
      prostate was excluded by digital rectal examination. When digital rectal
      examination was suspicious for carcinoma of the prostate and/or serum PSA > 4
      micrograms l-1, fine-needle aspiration biopsy was performed. Central values,
      values of variance and reference limits were defined by a non-parametric method
      in four age groups. A strong positive correlation between PSA values and age was
      found and the variance increased with age. The relationship between PSA value and
      age was non-linear. For the age group 56-60 the upper reference limit (95th
      percentile) was 4.6 micrograms l-1 (confidence interval, CI: 3.9-5.5). For the
      age groups 61-65, 66-70 and 71-75 the corresponding values were 4.4 (3.8-5.2),
      7.6 (6.5-8.9) and 8.4 micrograms l-1 (7.2-9.8) respectively. For the age groups
      studied the increment over time of the PSA value was 2-8% per year depending on
      age, with an average increment per year over 15 years of 4.3%. Overall, 11% of
      our reference sample had a serum PSA level > 4 micrograms l-1. We consider our
      study population to be representative for a normal Swedish male population in
      these age groups.

PMID- 9238759
TI  - Elimination of theophylline metabolites in healthy adults.
AB  - The metabolism of theophylline (TP) (540 mg per os) was determined by measuring
      plasma and saliva concentrations of TP and its metabolites, 0-24 h after loading,
      and urinary excretion 0-48 h after loading. TP and its five metabolites were
      separated and quantified by combining high-performance liquid chromatography and
      capillary electrophoresis. In addition to TP, 1,3-U, 3-X and 1-U were
      consistently found in plasma and saliva. The area under the plasma concentration
      time curve (AUC) showed that TP accounted for 91 +/- 4% (mean +/- SD) of the
      total AUC in plasma with 1,3-U accounting for 3.1 +/- 1.4%, 3-X for 3.4 +/- 1.8%
      and 1-U for 2.5 +/- 1.5%. The urine analyses showed that unchanged TP accounted
      for 19 +/- 5% of total excretion, the remainder being 1, 3-dimethyluric acid (1,3
      U, 41 +/- 6%), 1-methylxanthine (1-X, 2 +/- 0.8%), 1-methyluric acid (1-U, 26 +/-
      6%), 3-methylxanthine (3-X, 11 +/- 3%) and 3-methyluric acid (3-U, 1 +/- 0.3%).
      Highest excretion rates were observed for 1,3-U (70 +/- 29 mumol/h), 1-U (40 +/-
      26 mumol/h) and 3-X (20 +/- 15 mumol/h) 6-9 h after TP ingestion suggesting the
      high excretion of 1,3-U, 1-U and 3-X by the kidneys. The highest excretion rate
      of TP (50 +/- 8 mumol/h) occurring at 0-6 h after the load and rapidly declining
      thereafter, indicated the lower excretion of TP compared with its metabolites. N3
      demethylation of TP accounted for 34 +/- 6% of the urinary metabolites, N1
      demethylation of TP for 15 +/- 3% and C8-oxidation of TP for 51 +/- 9%. C8
      oxidation of 1-X and 3-X was 93 +/- 4%, and 9 +/- 4%, respectively, of the
      excreted amount of monomethylxanthine plus formed monomethylurate. Since the
      extent of all metabolic reactions remained constant during the load, it is
      suggested that TP is metabolized by hepatic reactions that occurred
      simultaneously and not sequentially.

PMID- 9238760
TI  - Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of
      glomerular filtration rate in pigs with reduced renal function: a comparison
      between different clearance techniques.
AB  - In order to simplify and/or improve determination of glomerular filtration rate
      (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were
      simultaneously determined with different techniques in 21 anesthetized landrace
      pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an
      intravenous bolus of the GFR markers, their plasma concentration curves were
      followed for 6 hours with 16 plasma samples. A bladder catheter collected urine
      during six 60-min periods. The plasma clearance was calculated by dividing "dose
      of marker" with "area under the plasma concentration curve" (AUC) from the time
      of injection to infinity using a one- (Clprovisional) and a three-compartment
      (ClAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated
      by dividing the amount of marker excreted in the urine in a period by AUC in the
      same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the
      total area in the period (Clren adv)-our reference method representing the "true"
      GFR and for creatinine determined by using the arithmetic mean of the plasma
      concentration of the marker at the start and at the end of the urine collection
      period (Clren simple). Renal clearance of creatinine was significantly lower than
      renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no
      significant differences between the renal clearances (Clren adv) of iohexol and
      51Cr-EDTA or between their plasma clearances (ClAUC-3comp). For iohexol the
      median overestimation of the "true" GFR with Clprovisional was higher when
      "early" plasma samples (30-120 min) were used (4.5 ml min-1 10 kg-1) than when
      late samples (180-360 min) were used (1.9 ml min-1 10 kg-1). Subtraction of the
      median extrarenal clearance (known from a study of nephrectomized pigs) from the
      plasma clearances (ClAUC-3comp) of iohexol and 51Cr-EDTA in pigs with reduced
      renal function decreased the median overestimation of the "true" GFR from 1.9 to
      1.0 ml min-1 10 kg-1 with iohexol and from 1.7 to 0.9 ml min-1 10 kg-1 with 51Cr
      EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by
      (i) including a "late" plasma sample in three- and one-compartment models, which
      tends to increase the AUC; (ii) introducing a correction formula by normalizing
      the GFR values of the one-compartment model to those of the three-compartment
      model, thereby compensating for the rapid early changes in plasma concentration
      of marker after the bolus injection of the marker; or (iii) subtracting a median
      (or mean) extrarenal clearance of the marker in pigs from the plasma clearance
      [according to (i) or (ii)]. The plasma clearance one-compartment technique may be
      improved in pigs with various levels of GFR values by normalizing the plasma
      clearance values to the renal clearance values, thereby compensating for both the
      early changes in plasma concentration of marker and the extrarenal clearance of
      marker.

PMID- 9238761
TI  - The effect of Losartan, an angiotensin II antagonist, on cardiac function, mass
      and morphology in rats after repeated hyperbaric exposures.
AB  - Previously, we have found development of left ventricular hypertrophy (LVH),
      myocardial necrosis and haemodynamic changes in rats after repeated hyperbaric
      exposures to 5 bar. Exactly the same rat model and experimental set-up was
      applied in the present study. The purpose of this study was to investigate if
      angiotensin II (Ang-II) plays a role in the development of these cardiac changes.
      Losartan, a recently developed non-peptide Ang-II receptor antagonist, was
      administrated (20 mg kg-1 day-1) to each rat for 40 days. Nine test rats
      underwent chamber dives daily for 40 consecutive days, and 10 control rats were
      exposed in the same chamber for an equal period of time, but in air at 1 bar.
      After 40 days, test rats and control rats had equal right and left ventricular
      myocardial mass/100 g-1 body mass, thus indicating that Losartan inhibits
      hyperbarically induced LVH. Microscopic examination revealed no changes in the
      left ventricle, indicating that Losartan prevents myocardial necrosis. The left
      ventricular pressure (LVP) and the maximal velocity of LVP increase and decrease
      (+/-dP/dt) were similar in the test rats compared to the control rats at 1 bar.
      Previously we found a higher LVP and dP/dt in non-treated test rats in otherwise
      identical experiments. This indicates that Losartan "normalizes" the cardiac
      function of test rats after repeated hyperbaric exposures. The systolic arterial
      pressure, heart rate (HR) and respiratory frequency (RF) were similar in the two
      groups at 1 bar. However, treatment with Losartan lowered the blood pressure
      compared to previously non-treated rats. In conclusion, long-term Ang-II receptor
      blockade prevented previously shown changes in cardiac function and morphology,
      as well as myocardial mass, after 40 consecutive exposures to 5 bar.

PMID- 9238762
TI  - Increased motility of Helicobacter pylori by methylcellulose could upregulate the
      expression of proinflammatory cytokines in human gastric epithelial cells.
AB  - The inflammatory reaction in the human gastric mucosa to Helicobacter pylori
      could be initially triggered by an array of cytokines expressed in infected
      gastric epithelial cells. The spiral morphology and flagella of these organisms
      could increase their velocity in a viscous environment such as methylcellulose
      solution. The goal of this study was to determine whether modification of H.
      pylori motility could influence the expression of cytokine genes from gastric
      epithelial cells infected with H. pylori. Adherent human gastric epithelial cells
      were cultured and overlaid with methylcellulose solutions of varying viscosity.
      These epithelial cell layers covered with methylcellulose solution were
      inoculated with H. pylori. RNAs were then extracted from the gastric epithelial
      cells. Various cytokine gene expressions were assessed and quantified by reverse
      transcription-polymerase chain reaction (RT-PCR) and standard synthetic RNA.
      Cytokine proteins were also measured by enzyme-linked immunosorbent assay
      (ELISA). Expression of mRNA for interleukin(IL)-8 was upregulated in H. pylori
      infected gastric epithelial cells overlaid with methylcellulose of 15 centipoise
      (cp) viscosity. The expression of mRNA for IL-1 alpha, IL-8, monocyte chemotactic
      protein (MCP)-1 and granulocyte macrophage colony-stimulating factor (GM-CSF) was
      also upregulated in H. pylori-infected gastric epithelial cells overlaid with
      methylcellulose solution of the same viscosity. The number of molecules of the
      expressed cytokine transcripts also paralleled the amounts of protein secreted
      from gastric epithelial cells infected with H. pylori. These results suggest that
      methylcellulose solution (simulating the mucus layer in vivo) could increase
      contact of H. pylori with gastric epithelial cells by increasing its motility.
      This could result in the upregulation of mRNA for proinflammatory cytokines in
      gastric epithelial cells, therefore enhancing inflammatory reaction at H. pylori
      infected sites.

PMID- 9238763
TI  - Hyperamylasemia due to macroamylasemia in adult gluten enteropathy.
AB  - We report hyperamylasemia due to macroamylasemia in a 33-year-old-woman with
      gluten enteropathy. Macroamylasemia was demonstrated by precipitation of 97% of
      amylase activity with PEG 6000. It was associated with increased serum IgA, with
      elevated values of specific IgA antibodies against alpha-gliadin and with a high
      titre of IgA anti-endomysium antibodies. Macroamylasemia disappeared after 2
      months of a strict gluten-free diet. These data suggest that the increased IgA
      concentration in adult gluten enteropathy led to increased macroamylase
      formation.

PMID- 9238764
TI  - A modification of the acid diazo coupling method (Malloy-Evelyn) for the
      determination of serum total bilirubin.
AB  - A simple and reliable method for the determination of total bilirubin from human
      serum is described. In this method, indirect bilirubin is liberated by the
      tenside in 0.12 mol l-1 HCl (R1), and the total bilirubin is coupled with a 2,5
      dichlorobenzene diazonium (DBD) salt to obtain the corresponding azobilirubin
      having a lambda max of about 520-522 nm. The method can easily be applied to the
      KONE Delta, a fully automated, discrete random access clinical analyser, and also
      to less modern instruments. A sample volume of 5 microliters, R1 volume of 180
      microliters, and R2 volume of 36 microliters was used on the KONE Delta. After a
      5-min incubation at 37 degrees C, measurement at 575 nm was done (main
      wavelength). The within-run imprecision (CV%) varied from 2.9 to 0.3% within the
      serum total bilirubin range of 14-290 mumol l (n = 10). The between-run
      imprecision was from 2.2 to 1.3% within the range 13-97 mumol l-1 (n = 8). The
      method is linear up to at least 340 mumol l-1 (19.8 mg dl-1), and dilution
      extends the test limit to 3400 mumol l-1 (198.8 mg dl-1). The linearity of
      dilution was good over the practical measuring range. The present method had a
      strong linear correlation with the Boehringer 2,5-dichlorophenyl diazonium (DPD)
      method on the Hitachi 717 analyser: y(DBD) = 1.018x(DPD)+0.758, r = 0.9955 (n =
      61). The stability of R2 (diazo reagent) in the analyser reagent compartment
      lasts at least 2 weeks.

PMID- 9238765
TI  - A review of sonographic identification of abdominal blood vessels and
      juxtavascular organs.
AB  - Abdominal vasculature can be evaluated non-invasively using 2-D ultrasound
      imaging and Doppler ultrasonography. The identification of abdominal vessels
      using ultrasound is based on knowledge of their normal location, appearance and
      relationship to specific organs. Because anatomic location of major abdominal
      vessels is fairly consistent, finding and following vessels is a useful aid when
      attempting to locate and evaluate juxta-vascular organs. Sonographic vascular
      evaluation may be beneficial in providing information regarding central
      cardiovascular abnormalities, detection of abnormalities involving the vessel
      interrogated, or detection of abnormalities of the parenchymal bed that the
      vessel supplies. Knowledge of the location and appearance of the vessels is
      necessary for this information to be of diagnostic value. In this paper,
      abdominal vessels in the dog are reviewed and a sonographic map of major
      abdominal vessels is described. This includes the sonographic appearance of the
      aorta, caudal vena cava, and protal vein, their major branches and their anatomic
      relationship with adjacent organs. Identification of the medial iliac lymph
      nodes, mesenteric lymph nodes, abdominal esophagus, duodenum, spleen, kidneys,
      pancreas, adrenal glands and liver lobes are assisted by recognizing specific
      vascular landmarks. The locations and appearances of pertinent organs as pertains
      to abdominal vasculature (caudal vena cava and aorta) are described.

PMID- 9238766
TI  - Pet fish radiography: technique and case history reports.
AB  - Radiography can be used to aid in the diagnosis and treatment of pet fish
      diseases. Handling, restraint and radiographic technique for the radiographic
      examination of pet fish is described. Quality diagnostic images can be obtained
      with standard radiographic equipment and radiographic techniques. Fishes with
      undifferentiated sarcoma, swim bladder herniation and scoliosis are three
      clinical examples that are described where radiography was used in the management
      of the patient. Conventional radiography appears to be best for evaluating
      skeletal and swim bladder diseases. Alternate imaging techniques such as computed
      tomography and magnetic resonance imaging may enhance the evaluation of coelomic
      soft tissue structures.

PMID- 9238767
TI  - Hydromyelia in the dog.
AB  - Hydromyelia is a dilation of the spinal cord central canal. In man this may be
      due to congenital malformations such as Dandy-Walker syndrome and Chiari
      malformations or may be acquired as result of infection, trauma or neoplasia. In
      dogs hydromyelia may be accidentally diagnosed during routine cisterna magna
      myelography. Hydromyelia, and its possible etiology, may be confirmed by means of
      computed tomography or magnetic resonance imaging. Three dogs with hydromyelia
      due to differing etiologies are described.

PMID- 9238768
TI  - Diagnosis of C5-C6 spinal luxation using three-dimensional computed tomographic
      reconstruction.

PMID- 9238769
TI  - The effect of prepuberal and postpuberal gonadectomy on radial physeal closure in
      male and female domestic cats.
AB  - Male (n = 6/group) and female (n = 6/group) kittens were gonadectomized at 7
      weeks (prepuberally) or 7 months of age (postpuberally), or left intact. Lateral
      radiographic projections of the right forelimb were made from 4 months of age
      until the distal radial physis was closed, or 24 months of age. In males, distal
      radial physeal closure was delayed in both groups of gonadectomized animals,
      compared to intact males (p < 0.01). In females, proximal radial physeal closure
      was significantly delayed in prepuberally gonadectomized animals (p = 0.02), and
      distal radial physeal closure was significantly delayed in both groups of
      gonadectomized animals, compared to intact animals (p < 0.01). Final radial
      length (females p < 0.01, males p = 0.01), and age and radial length at time of
      the growth plateau (p < 0.01) were significantly increased in all gonadectomized
      animals. Age at gonadectomy had no effect on age and radial length at time of the
      growth plateau. No puberal growth spurt was observed in any of the cats.

PMID- 9238770
TI  - Radiographic diagnosis--aberrant bone growth following phalangeal fracture.

PMID- 9238771
TI  - Lateral collateral ligament avulsion of the humeroradial joint in a horse.
AB  - This report describes traumatic avulsion of the lateral collateral ligament of
      the humeroradial joint in a horse. The history and diagnostic procedures are
      included with relevant radiographs and ultrasonographs. The poor prognosis
      associated with this injury is due to degenerative joint disease.

PMID- 9238772
TI  - Ultrasonographic evaluation of renal size in dogs with acute allograft rejection.
AB  - The purpose of this study was to determine the best method to
      ultrasonographically monitor renal size changes associated with acute allograft
      rejection in dogs. Qualitative changes in renal cortical and medullary
      echogenicity were also evaluated, although this was not a major focus of the
      study. Four unrelated, mixed-breed dogs underwent bilateral nephrectomies and
      heterotopic renal allograft transplantation. Ultrasound examinations of
      transplanted kidneys were initiated at 3 days after surgery and continued at 2-3
      day intervals until death (38 +/- 2 days). Ultrasound measurements of kidney
      length, width, height, cross-sectional area, and estimated volume were used to
      assess relative changes in renal size associated with transplantation and
      rejection. Transplanted kidneys had a rapid increase in volume and cross
      sectional area that averaged 103% and 83% above baseline levels, respectively, by
      17 days after transplantation. The increased size was attributed to a combination
      of hypertrophy and acute rejection, the latter of which was confirmed at
      postmortem. Kidney volume decreased to approximately 35% above baseline volume by
      day 34 as rejection became more advanced. Qualitative changes associated with
      rejection included medullary enlargement with decreased echogenicity early in the
      study, followed by increased cortical thickness and echogenicity with poor
      cortical medullary definition in the latter stages of the survival period. It was
      concluded that relative changes in renal allograft size can be easily monitored
      with ultrasound. In regard to linear measurements, changes in renal width were
      more pronounced than changes in height or length with acute rejection. Therefore
      measurements that incorporate the width, namely volume or cross-sectional area,
      appear to be the most sensitive for monitoring changes in allograft size. Renal
      cross-sectional area measurements are preferred because they are simple to
      perform using the automated calculation capability of most newer ultrasound
      units.

PMID- 9238773
TI  - Ultrasonic examination of the pancreas in healthy cows.
AB  - The purpose of this study was to describe the ultrasonographic appearance of the
      normal bovine pancreas and to establish reference values for healthy cattle.
      Ultrasonographic examinations were performed on the right side of 20 healthy
      cows. Ultrasonographically the body and right limb of pancreas appeared as a
      triangle-shaped structure associated with the liver, portal vein, right kidney,
      and duodenum. In comparison to normal liver, the pancreas appeared isoechoic or
      slightly more echogenic. The right lobe of the pancreas was evaluated from the
      right flank to the eleventh intercostal space, and the body of the pancreas was
      visualized from the twelfth to the tenth intercostal space. The left lobe of the
      pancreas could not be seen because of its dorsomedial location. In 9 cows, the
      accessory pancreatic duct was located near the right lobe of the pancreas and
      appeared as two parallel echogenic lines with a hypoechogenic area between them.
      The diameter of the accessory pancreatic duct varied from 6 to 8 mm. The
      pancreaticoduodenal vein was seen in 5 cows. The diameter of the
      pancreaticoduodenal vein varied from 3 to 4 mm. The ultrasonographic
      characteristics determined in this study may serve as a reference in the
      evaluation of cows with suspected pancreatic disease.

PMID- 9238774
TI  - Adrenal ultrasonography correlated with histopathology in ferrets.
AB  - The adrenal glands of twenty-six, 12- to 53-month-old, ferrets without clinical
      signs of adrenal disease were examined and measured by ultrasonography and the
      findings compared with those from gross examination and histopathology. Of 51
      adrenal glands examined, 27 were normal, 23 had either nodular or diffuse
      cortical hyperplasia and 1 had an adenocarcinoma. There was no statistically
      significant difference between the sonographic nor gross size of normal adrenal
      glands and those with hyperplasia. Moderate correlation was found between gross
      and sonographic measurements of length for both right (r = 0.783; p < 0.0001) and
      left (r = 0.609; p < 0.001) and width (p < 0.02). In female ferrets, the length,
      width, and depth of the right adrenal gland sonographically measured (mean +/-
      sd) 7.5 +/- 1.2 mm, 3.7 +/- 0.6 mm, 2.8 +/- 0.4 mm, respectively, and the left
      measured 7.4 +/- 1.0 mm, 3.7 +/- 0.4 mm, 2.8 +/- 0.4 mm; in males, the right
      adrenal measured 8.9 +/- 1.6 mm, 3.8 +/- 0.6 mm, 3.0 +/- 0.8 mm and the left
      measured 8.6 +/- 1.2 mm, 4.2 +/- 0.6 mm, 3.0 +/- 0.6 mm. Accessory adrenal tissue
      was not identified during the sonographic examination but was grossly found in 10
      of the ferrets. It was associated with either the right, left or both adrenal
      glands.

PMID- 9238775
TI  - Application of the pin-hole collimator in small animal nuclear scintigraphy: a
      review.
AB  - The pin-hole collimator is used to improve spatial resolution and magnify areas
      of interest. The pin-hole collimator has many applications in small animal
      veterinary scintigraphy. The principles of image formation for the pin-hole and
      parallel hole collimators are reviewed. The effects of distance on resolution and
      sensitivity are presented for the pin-hole and parallel hole collimators.
      Specific application of the pin-hole collimator in veterinary scintigraphy are
      discussed.

PMID- 9238776
TI  - Radiographic evaluation of caudal vena cava size in dogs.
AB  - Dilation of the caudal vena cava (CVC) on lateral thoracic radiographs is often
      interpreted as suggestive of right-sided congestive heart failure. To quantitate
      the clinical utility of evaluating CVC size as an indicator of right-sided heart
      disease, we compared the ratio of the diameter of the CVC as measured on a left
      lateral thoracic radiograph to the descending aorta (Ao), length of the thoracic
      vertebra above the tracheal bifurcation (VL), and width of the right fourth rib
      (R4) in 35 dogs with right heart disease and 35 control dogs. Each CVC ratio
      (CVC/Ao, CVC/VL, CVC/R4) was statistically larger in dogs with right heart
      disease. Response operating characteristic curves and likelihood ratios were used
      to determine ratios helpful in identifying dogs with right heart disease. A
      CVC/Ao > 1.50, CVC/VL > 1.30, or CVC/R4 > 3.50 are strongly suggestive of a right
      sided heart abnormality in a patient.

PMID- 9238777
TI  - Magnetic resonance imaging of the brain of normal neonatal foals.
AB  - Magnetic resonance imaging (MRI) was performed on the brain of 5 normal,
      anesthetized, neonatal (age 3-to-6 days) Quarter Horse foals. The objectives of
      the study were to develop a technique for imaging the brain of neonatal foals,
      and to ascertain their normal brain anatomy. Intravenous propofol was
      administered for induction and maintenance of general anesthesia. Using spin echo
      MR techniques, T1 weighted sagittal and transverse views, and spin density and T2
      weighted transverse views were successfully made of each foal. MR images provided
      excellent visualization of many anatomic structures of the brain and head. MRI of
      the brain is feasible for selected neonatal equine patients.

PMID- 9238778
TI  - Cerebral sinus venography in the dog: a new technique.
AB  - A new method of performing cerebral sinus venography was developed that opacifies
      both the ventral and most of the dorsal venous sinus systems. A pediatric
      angiographic catheter was introduced into the external jugular vein and advanced
      to the level of the temporal sinus. Iodinated contrast medium was injected
      manually and radiographs were made. Subtraction radiography was used to visualize
      vessels filled with contrast medium. Venography was simple and relatively non
      invasive and was considered safe. The technique was used to confirm occlusion of
      the transverse venous sinus in healthy dogs that had undergone radical
      craniectomies.

PMID- 9238779
TI  - True diaphragmatic hernia in a cat.
AB  - A report of a cat with a true diaphragmatic hernia in which only falciform fat
      had herniated is presented. The lesion was misinterpreted as a pulmonary mass.
      Additional radiographic studies which may have been of diagnostic benefit are
      briefly discussed.

PMID- 9238781
TI  - Ultrasonographic adrenal gland measurements in dogs without evidence of adrenal
      disease.
AB  - The purpose of this retrospective study was to determine measurements of adrenal
      glands from longitudinal sonograms, in a large population of dogs and to
      correlate these measurements to age, sex and descriptors of body size. Dogs were
      selected from the clinic population presented for routine abdominal
      ultrasonography between September, 1991 and March, 1994. Dogs with elevated serum
      cholesterol or alkaline phosphatase levels, polyuria/polydipsia, and/or clinical
      diagnoses of adrenal pathology were excluded. Dogs with ultrasound-documented
      abnormalities (mass lesions, abnormal architecture) of either adrenal were not
      considered. Age, sex, weight and breed were recorded, and the body surface area
      of each dog was calculated. Adrenal length and caudal polar width were determined
      from longitudinal, two-dimensional ultrasound images. Adrenal measurements were
      compared with body size measurements and age using least squares linear
      regression analysis and the correlation coefficient (r) and coefficient of
      determination (r2) calculated. One hundred and ninety three dogs were included in
      the study, with a weight and body surface area range of 1.8-72 kg and 0.2-1.8 m2,
      respectively. The left adrenal gland (n = 182) length range was from 10.7 to 50.2
      mm, and the range of the caudal polar widths was 1.9 to 12.4 mm. Right adrenal
      gland (n = 85) length range was from 10 to 39.3 mm, and the range of the caudal
      polar widths was from 3.1 to 12 mm. In dogs where both adrenal gland lengths were
      measured (n = 74), the right adrenal gland length was less than that of the left
      in 46 dogs, equal to the left in one dog, and greater than the length of the left
      in 27 dogs. The strongest linear association was noted between the left adrenal
      gland length and body weight (kg, r = 0.71, p < 0.0001) or body surface area (m2,
      r = 0.71, p < 0.0001). Similar significant association was noted between the
      right adrenal gland length and body weight (kg, r = 0.69, p < 0.0001). A
      significant positive association was also noted between age and left adrenal
      gland length, (r = 0.25, p = 0.009). The summation of all four adrenal
      measurement values (left length and width, right length and width) did slightly
      improve the correlation (r = 0.74, p < 0.0001) when compared with body weight
      (kg). There was not a significant difference in the adrenal measurements with
      regard to sex. With regard to the correlation coefficient values, there was no
      advantage noted to calculating the body surface area from body weight. The causes
      for the low degrees of the correlation between adrenal size and the variables
      investigated in this study are unknown; measurement error, effects of non-adrenal
      illness on adrenal size, and a non-linear or complex linear relationship between
      adrenal gland size (as measured by longitudinal parameters) and descriptors of
      body size are among possible explanations.

PMID- 9238780
TI  - Parosteal osteosarcoma of the cervical vertebra in a dog.
AB  - A 12-year-old Maltese terrier was evaluated for progressive tetraparesis and neck
      pain. On radiographs, there was a periosteal reaction involving the fourth
      cervical vertebra. Myelographically, there was extradural compression of the
      spinal cord associated with the lesion. The dog was euthanized and necropsied.
      Histopathologic diagnosis was parosteal osteosarcoma of the vertebra.

PMID- 9238782
TI  - Sonographic evaluation of urinary bladder wall thickness in normal dogs.
AB  - Urinary bladder wall thickness was evaluated by ultrasonography in 16 normal
      dogs. Sterile saline solution was administered via urinary catheters to control
      the degree of bladder distention. Bladder wall thickness was measured on static
      ultrasound images in 4 locations and at 3 degrees of bladder distention (minimal,
      mild, and moderate). Four randomized distention sequences with 3 distentions per
      sequence were performed on each dog and the data were analyzed using Williams'
      balanced Latin square. Mean bladder wall thickness was 2.3 mm in minimally
      distended bladders (0.5 ml/kg saline), 1.6 mm in mildly distended bladders (2
      ml/kg saline) and 1.4 mm in moderately distended bladders (4 ml/kg saline). Mean
      bladder wall thickness increased significantly with increasing body weight and
      with decreasing bladder distention. The caudoventral measurement location
      produced a statistically significant smaller measurement, with a difference of
      0.3 mm. Sex did not affect bladder wall thickness. Distention sequence and
      repetition of distentions did not affect bladder wall thickness.

PMID- 9238783
TI  - Sonography of the musculoskeletal system in dogs and cats.
AB  - Sonography of the musculoskeletal system in dogs and cats was undertaken to
      evaluate the application of this imaging procedure in orthopedics. In most of the
      patients a 7.5 MHz linear transducer was used because of its flat application
      surface and its resolving power. The evaluation of bone by sonography is limited,
      but sonography can provide addition information regarding the bone surface and
      surrounding soft tissue. Ultrasound is valuable for assessing joint disease.
      Joint effusion, thickening of the joint capsule and cartilage defects can be
      identified sonographically. It is also possible to detect bone destruction.
      Instabilities are often identified with the help of a dynamic examination. Soft
      tissue abnormalities of the musculoskeletal system lend themselves to sonographic
      evaluation. Partial or complete muscles or tendon tears are able to be
      differentiated and the healing process can be monitored. Most of the diseases
      that are in the area of the biceps or the achilles tendon, such as dislocation of
      the tendon, old injuries with scarification, free dissecates in the tendonsheath,
      tendinitis and/or tendosynovitis can be differentiated by sonography. In
      addition, with clinical and laboratory findings, it is often possible to make a
      correct diagnosis with ultrasound in patients with abscesses, foreign bodies,
      hematomas, soft tissue tumors and lipomas.

PMID- 9238785
TI  - Artifacts and technical errors presented as part of the 1996 ACVR oral
      certification examination.
AB  - Cases used for the examination consisted of various imaging artifacts and
      technical errors. The candidate was expected to name or identify the problem and
      discuss its cause and prevention. For the purpose of completeness, the scope and
      detail given here is in excess of that needed to pass the examination. Unless the
      problem was obvious, the examiner pointed out the problem to be discussed.

PMID- 9238784
TI  - The use of radionuclide angiography to study blood flow through endothelial cell
      seeded extrathoracic bypass grafts in the dog.
AB  - Endothelial seeding of vascular grafts has been shown to decrease graft
      thrombogenicity and prolong longevity when implanted in vivo. Previous studies
      have utilized anatomic grafts to study endothelialization and healing. Anatomic
      thoracoabdominal grafts do not allow for sequential biopsy for evaluation of
      individual grafts nor do they approximate the environment for long bypass grafts
      used in limb salvage. This study evaluated the use of an extra-anatomic aortic
      bypass graft to assess the healing of endothelial cell seeded expanded
      polytetrafluoroethylene (ePTFE). Radionuclide angiography was used to evaluate
      graft patency and quantify blood flow through the graft. Dogs underwent placement
      of an extra-anatomic 60 cm long, 8 mm internal diameter, graft seeded with
      autologous endothelium. Grafts were biopsied from 2 weeks up to 1 year.
      Radionuclide studies were performed postimplantation and following each graft
      biopsy. Graft placement and biopsies were well tolerated in all dogs. Biopsied
      segments of graft allowed for sequential studies of the healing of implanted
      grafts by scanning electron and light microscopy. Flow through the implanted
      graft was close to 50% of the total caudal abdominal aortic flow. No significant
      difference in graft flow was noted either between animals or over time.

PMID- 9238786
TI  - Magnetic resonance imaging and computed tomography characteristics of
      intracranial intra-arachnoid cysts in 6 dogs.
AB  - Magnetic resonance imaging (MRI) and computed tomographic imaging (CT)
      characteristics of intracranial intra-arachnoid cysts in six dogs are described.
      Of the six dogs, three were less than one year of age and 4 were males. Five of
      the six dogs weighed less than 11 kg. Five cysts were located in the
      quadrigeminal cistern. On CT images, the intracranial intra-arachnoid cysts had
      sharply defined margins, contained fluid isodense to CSF and did not enhance
      following i.v. administration of contrast. On MRI images, the intracranial intra
      arachnoid cysts were extra-axial, contained fluid isointense with CSF and did not
      enhance following i.v. contrast. While spinal arachnoid cysts of dogs have been
      reported in the literature, other than the six dogs contained in this report,
      intracranial intra-arachnoid cysts have not to our knowledge been described in
      animals. These six dogs have a similar age, sex, history, clinical signs, CT and
      MRI findings to those reported in people with intracranial intra-arachnoid cysts.

PMID- 9238788
TI  - Radiographic appearance of the middle ear after ventral bulla osteotomy in five
      dogs with otitis media.
AB  - Radiographs of the middle ear were made in five dogs 60 to 78 months after
      ventral bulla osteotomy was performed to treat otitis media. The clinical results
      of surgery were considered satisfactory in four dogs and unsatisfactory in one.
      In 4 dogs with satisfactory results, radiographs demonstrated complete
      reformation of the bulla in 3 operated middle ears (3 dogs), with partial bulla
      reformation in the three middle ears (3 dogs). Radiographs in one dog with
      unsatisfactory results showed complete bulla reformation with no increase in
      lumen opacity. The proliferative bony response obliterating the middle ear
      previously reported in normal dogs after ventral bulla osteotomy was not seen in
      any of these patients.

PMID- 9238787
TI  - Radiographic, computed tomographic and magnetic resonance imaging evaluation of a
      chronic long digital extensor tendon avulsion in a dog.
AB  - Long digital extensor tendon avulsion is reported in a 5 month old Great Dane.
      Clinically the dog presented with a unilateral weight-bearing pelvic limb
      lameness. Joint effusion was present and there was pain and crepitance associated
      with flexion of the stifle. Orthopedic evaluation and radiographs were suggestive
      of a long digital extensor tendon injury which was confirmed by computed
      tomography and magnetic resonance imaging. The injury was surgically repaired
      with screw and spiked washer fixation.

PMID- 9238790
TI  - Magnetic resonance imaging of the equine metacarpophalangeal joint: three
      dimensional reconstruction and anatomic analysis.
AB  - Magnetic resonance imaging was used to examine the equine metacarpophalangeal
      joint. Thirty-two saggital images generated by partial volume imaging were
      transferred to a computer for three-dimensional reconstruction and analysis. All
      the tissues constituting the metacarpophalangeal joint were readily identified.
      The most significant increase finding regarded the soft tissues on the palmar
      aspect of the metacarpophalangeal joint and their interactions with the proximal
      sesamoid bones. The equine metacarpophalangeal joint has not previously been
      evaluated using 3-dimensional imaging software.

PMID- 9238789
TI  - A myelographic technique for avian species.
AB  - A post-mortem myelogram was used to diagnose a vertabral fracture in a Red-tailed
      Hawk (Buteo jamaicensis). This diagnosis led the authors to believe that
      myelography would be useful in live birds. In a pilot study using live adult
      female chickens (Gallus domesticus), mammalian myelographic techniques were
      modified for avian anatomic differences. A thoracolumbar puncture site was used
      rather than the lumbar or cisternal site which is commonly used in mammals. The
      volume of contrast medium needed to produce a diagnostic myelogram in birds (0.8
      1.2 ml/kg) was found to be approximately four times that needed in mammals. A 25
      gauge spinal needle was used rather than a 23 gauge needle. Myelograms of
      diagnostic quality were obtained with normal subject recovery. Seizures, the most
      common post-myelographic complication in mammals, were not observed in any of the
      birds studied. Avian myelography was found to be a cost effective and humane
      technique with potential application to avian practice.

PMID- 9238791
TI  - Pulsed wave-Doppler ultrasonographic evaluation of the common carotid artery in
      the resting horse: physiologic data.
AB  - A pulsed wave-Doppler ultrasonographic evaluation of common carotid arterial
      blood flow was carried out on 63 healthy Italian Saddlebred horses. Vessel
      diameter and tracing morphology were evaluated and blood flow parameters
      (systolic, diastolic and mean velocity, acceleration and deceleration of the
      systolic wave, carotid pulse volume) were calculated and correlated with class
      variables (sex, age and body weight). On the basis of the presence of an incisure
      in the ascending branch of the systolic curve, subjects were divided in two
      groups: one with a bifid systolic curve and the other with a monophasic aspect.
      Correlations between: 1) diameter of the vessel and body weight and 2) carotid
      pulse volume and flow velocity (systolic, diastolic and mean) were found. A
      greater systolic pulse volume was found in male subjects, in subjects with
      greater body weight and in those which had a monophasic systolic wave.

PMID- 9238792
TI  - Ultrasound/computed tomography diagnosis--fungal sinusitis and retrobulbar
      myofascitis in a cat.

PMID- 9238793
TI  - Scintigraphic assessment of distal extremity perfusion in 17 patients.
AB  - To assess the role of scintigraphic evaluation of distal limb perfusion, the
      medical records and scintigraphic perfusion images of 17 animals (8 dogs, 2 cats,
      2 calves, 4 birds and 1 ferret) with clinical signs of distal limb ischemia were
      examined retrospectively. Images were obtained at 5 and 10 minutes following
      injection of 99mTc-MDP, or 99mTc-DTPA. The initial scintigraphic diagnoses of 17
      animals included complete ischemia (8/17), partially reduced perfusion (5/17),
      and normal to increased perfusion (4/17). In 4 of the animals with partially
      reduced perfusion, follow-up scans indicated progression to complete ischemia
      (1/4) or normal to increased perfusion (3/4). Nine of 17 animals had a final
      scintigraphic diagnosis of complete distal limb ischemia, and these animals were
      either euthanized (5/9) or had limb amputation (4/9). A final diagnosis of
      complete ischemia was supported with either repeat scanning (3/10), continued
      clinical observation (6/10) and/or pathological examination (10/10). Clinical
      signs of ischemia resolved in all (7/17) animals with increased or normal
      perfusion on their final scan. Scintigraphy provided a safe and noninvasive
      assessment of distal limb perfusion, which corresponded with clinical outcome.

PMID- 9238794
TI  - Scintigraphic evaluation of four dogs with protein-losing enteropathy using
      111indium-labeled transferrin.
AB  - The purpose of this study was to determine the clinical utility of 111In-labeled
      transferrin (111In-TF) scintigraphy for evaluating dogs suspected of having
      protein-losing enteropathies. Four dogs were injected intravenously with
      autologous 111In-TF after 30 min incubation (at 37 degrees C) of 18.5 MBq (0.5
      mCi) 111InCl3 with one ml of autologous plasma. Serial right lateral, left
      lateral and dorsal images were obtained 2, 4, and 24 hours post 111In-TF
      administration. Images were subjectively evaluated for the presence or absence of
      111In-TF within the gastrointestinal tract. The results of total protein, albumin
      and globulin levels and results from gastrointestinal biopsies were recorded. In
      one dog, a follow-up scintigraphic study was done six months after initial
      evaluation and initiation of treatment for plasmocytic-lymphocytic enteritis.
      Gastrointestinal activity was noted by two hours in two dogs, while all four dogs
      had gastrointestinal activity on the 24 hour images. The mean (+/-std dev) plasma
      protein, albumin and globulin levels were 3.5 (+/-0.9), 1.7 (+/-1) and 1.8 (+/
      0.3) respectively at the time of initial presentation. In the one dog that was
      evaluated after therapy, faint visualization of radioactivity within the colon
      was noted on the 24 hour image. Based on this study, 111In-TF appears to be a
      viable scintigraphic method for evaluating dogs with suspected protein-losing
      enteropathies. Potential limitations of this radiopharmaceutical include cost and
      prolonged isolation of the animal prior to release to the client due to the long
      physical half-life (T1/2 = 2.82 days).

PMID- 9238795
TI  - First-pass radionuclide angiography in the diagnosis of aortoiliac
      thromboembolism in a horse.
AB  - First-pass radionuclide angiography of the terminal aorta was performed in 3
      normal horses and a 6-year-old Standardbred intact male with aortoiliac
      thromboembolism. Thromboembolism caused chronic bilateral hind limb lameness,
      more severe in the right hind limb, was detected by rectal examination, and
      confirmed using transrectal ultrasonography. Using 99mTc-HDP, first-pass
      radionuclide angiography was combined with hind limb and pelvis bone (delayed)
      scintigraphy and revealed marked reduction in blood flow through both external
      iliac arteries and absence of blood flow in the internal iliac arteries.
      Quantitative analysis showed a decreased activity in the right iliac vessels in
      the clinic patient consistent with reduced blood flow when compared to control
      horses. First-pass radionuclide angiography provided a method to obtain
      diagnostic images of the terminal aorta and branches and a method to diagnose
      aortoiliac thromboembolism in the horse.

PMID- 9238797
TI  - [Related living donor for liver transplantation in children: results and impact].
AB  - Encouraging results of alternative techniques used for liver transplantation in
      children (liver reduction) and the persistent lack of a sufficient number of
      cadaver donors has favored the development of living related donor liver
      transplantation. This program, which began after a long preparative period
      concerning the ethical questions involved, has included 32 children during the
      first 30 months. Results have been excellent. All children who underwent elective
      transplantations (n = 18) are still living. Among the 14 patients whose condition
      required hospitalization before transplantation, 86% have survived. Vascular
      complications and graft loss due to primary dysfunction or chronic rejection have
      been reduced, but 22% of the patients have biliary stenosis. In the donors, there
      has been no severe complication or sequelae. Use of related living donor livers
      has increased the number of grafts available for children on the waiting list for
      cadaver livers. The resulting gain in waiting time has also reduced the risk of
      death before transplantation. In our experience, the combination of the two
      transplantation programs using living donors and cadaver livers has had a
      positive impact on global management of children referred for liver
      transplantation, whatever the option chosen by the parents.

PMID- 9238796
TI  - Changes in renal function in cats following treatment of hyperthyroidism using
      131I.
AB  - Changes in renal function of twenty-two cats treated for hyperthyroidism using
      radioiodine were evaluated. Serum thyroxine (T4), serum creatinine, blood urea
      nitrogen (BUN) and urine specific gravity were measured before treatment and 6
      and 30 days after treatment. Twenty-two cats had pretreatment and 21 cats had 6
      day posttreatment measurement of glomerular filtration rate (GFR) using nuclear
      medicine imaging techniques. There were significant declines in serum T4 at 6
      days following treatment, but the changes in GFR, serum creatinine and BUN were
      not significant. At 30 days following treatment, there were significant increases
      in BUN and serum creatinine and further significant declines in serum T4. Nine
      cats were in renal failure prior to treatment and 13 cats were in renal failure
      30 days following treatment. Renal failure was defined as BUN greater than 30
      mg/dl and/or serum creatinine greater than 1.8 mg/dl with concurrent urine
      specific gravity less than 1.035. These 13 cats included eight of 9 cats in renal
      failure prior to treatment and 5 cats not previously in renal failure. Follow up
      information beyond 30 days following treatment on 9 of these 13 cats indicated
      that all remained in renal failure. Based on receiver operating curve analysis of
      pretreatment glomerular filtration rate (GFR) in predicting posttreatment renal
      failure, a value of 2.25 ml/kg/min as a point of maximum sensitivity (100%) and
      specificity (78%) was derived. Fifteen of 22 cats had pretreatment GFR
      measurements of less than 2.25 ml/kg/min. These 15 cats included all 9 cats in
      renal failure and 5 cats with normal renal clinicopathologic values prior to
      treatment. At 30 days following treatment, 13 of these 15 cats were in renal
      failure. The 2 cats not in renal failure had persistently increased serum T4
      values. Seven of 22 cats had pretreatment GFR measurements greater than 2.25
      ml/kg/min. None of these 7 cats was in renal failure at 30 days following
      treatment, all cats having normal BUN, serum creatinine, and urine specific
      gravity values. It was concluded that significant declines in renal function
      occur after treatment of hyperthyroidism and this decline is clinically important
      in cats with renal disease. Pretreatment measurement of GFR is valuable in
      detecting subclinical renal disease and in predicting which cats may have
      clinically important declines in renal function following treatment.

PMID- 9238798
TI  - [Surgical treatment of intrahepatic cholangiocarcinoma].
AB  - Cholangiocarcinoma is the second most frequent malignant tumor, after
      hepatocarcinoma, of the liver; it is diagnosed in approximately 10% of the cases.
      This retrospective study reviewed follow-up in 50 patients with intrahepatic
      cholangiocarcinoma treated from June 1979 through February 1993. Among these 50
      patients, 32 underwent liver resection and 18 had a liver transplantation. After
      resection, the median survival was 13.9 months. Tumor stage was seen to have an
      effect on the Kaplan-Meier plots although the differences were not significant.
      Four patients died from tumor recurrence more than five years after curative
      resection, 4 patients are living today. After transplantation, the median
      survival was 5 months. Among the 18 patients, 1 recipient who had a stage II
      tumor is currently living 42 months after transplantation with no evidence of
      recurrence. Despite the high degree of malignancy of intrahepatic
      cholangiocarcinoma, a certain number of patients do benefit from liver resection,
      justifying this aggressive surgical approach. Inversely, transplantation does not
      appear to be an exceptional therapeutic alternative. In the future,
      cholangiocarcinomas will require multimodal therapeutics.

PMID- 9238799
TI  - ["Mini-invasive" surgery of the abdomen in 1996].
AB  - Intracavitary abdominal and thoracic operations as well as endoluminal
      procedures, guided or assisted by videoendoscopic techniques through minimal
      access sites have the following goals: Diagnosis, excision only of an organ,
      excision followed by reconstruction, repair only. The indications are well
      established for diagnostic procedures and organ excisions only. They are being
      defined for excisions and repair or repair only by present, widespread clinical
      activities and participation in prospective randomized clinical trials. The
      author presents recommendations for a variety of operations in each one of the
      four groups.

PMID- 9238800
TI  - [Primary hyperparathyroidism. Optimization of surgical results with systematic
      preoperative 99mTc-Sestamibi scintigraphy].
AB  - OBJECTIVE: The importance of preoperative 99mTc Sestamibi (MIBI) scintigraphy in
      case of reoperation for persistent hyperparathyroidism is well recognized, but it
      use as a systematic exploration technique remains a question of debate. We
      conducted this study to determine whether preoperative MIBI scans performed in
      all cases before surgery have any real impact. METHOD: Two successive series of
      65 operated patients were included in the study. In the first group, the MIBI
      scan was not performed prior to surgery while in the second group the MIBI scan
      was part of the systematic work-up. RESULTS: The sensitivity and positive
      predictive value of MIBI were 92% and 96% respectively. Sensitivity for unique
      adenomas was 95% and 80% for multiple forms. In the first group without
      systematic scans, there were two unproductive procedures. In the second group,
      all procedures were productive and no reoperations were required. Two mediastinal
      adenomas were removed at the first cervicotomy in this group. The rate of
      complications was similar for both groups. Mean operation time was 2 hours in the
      first group and 1 hour 30 minutes for the second. CONCLUSION: Our series shows
      that there are three main advantages of using MIBI scintigraphy systematically
      prior to surgery for hyperparathyroidism: the procedure is easier in patients
      with cervical adenomas, particularly in case of ectopic localizations; the mean
      duration of the operation is shortened by 30 minutes; mediastinal ectopic
      localizations can be removed by sternotomy at the first operation. These
      advantages appear to be great enough to propose systematic use of MIBI scan prior
      to surgery. When MIBI scan shows a single gland, the risk of missing a multiple
      localization is less than 2% in our experience. It appears possible to operate
      under local anesthesia via a single-sided approach in elderly patients or high
      risk patients.

PMID- 9238801
TI  - [Adrenal gland resection with laparoscopy or lumboscopy. The Paris experience].
AB  - A survey of 7 surgeons in Paris collected 173 cases of adrenal gland resection
      using laparoscopes or lomboscopes in 164 patients. Video-assisted surgery
      techniques were used in the past 4 years for: Conn's syndrome (n = 69),
      fortuitously observed tumors (n = 39), Cushing's syndrome (n = 24),
      phyeochromocytoma (n = 18) and Cushing's disease (n = 4). There were 155
      unilateral tumors and 9 bilateral tumors in patients with Cushing's disease. This
      survey showed that conversion rate was 14% and local complications rate 2.4%,
      mean operative time for unilateral operations was 144 minutes (range 50-240) and
      266 minutes (range 125-480) for bilateral tumors. Although this was a
      retrospective uncontrolled survey, pain relief and hospitalization time were
      greatly improved over traditional open surgery. The difference between the
      transperitoneal and the retroperitoneal route could not be evaluated due to
      differences in the number of patients for which each technique was used. Surgeon
      experience varied greatly, but it appears that video-assisted adrenal gland
      surgery is the preferred route due to reduced risk and improved post-operative
      period. Tumors with a diameter greater than 6 cm and malignant or suspected
      malignant tumors still require open surgery.

PMID- 9238802
TI  - [My experience in repairing, without tension, primary inguinal hernia in men].
AB  - Beginning in 1990, the tension-free inguinal hernioplasties were adopted for the
      treatment of primary groin hernias in men. 1252 tension-free hernioplasties were
      performed in 1,076 men and followed for one to six years. Lichenstein's tension
      free hernioplasty and Gilbert's sutureless hernioplasty were used, usually in
      combination. Anesthesia was local in 97% of the operations. 15 complications
      occurred (1.2%): one wound infection, one seroma, 12 hematomas, and one
      ilioinguinal neuralgia, 6 recurrences occurred (0.5%): 4 indirect, one direct and
      one femoral. No indirect recurrences have occurred since placing Gilbert's cone
      shaped plug in the deep ring. Tension-free hernioplasties consisting of a patch
      of polypropylene mesh plus a cone plug of the same material, placed in the deep
      ring when an indirect hernia is present, produce excellent results and are the
      preferred methods to manage the majority of primary inguinal hernias in men.

PMID- 9238803
TI  - [Surgical activity in health care facilities].
AB  - Surgical activity for 144,000 beds in 1605 health care facilities in France in
      1992 are reported. Both public (49%) and private (51%) hospital beds were
      studied. There were 2456 surgical theaters and a representative sample of 450,000
      operations was examined. There were 4723 authorized beds which were not installed
      and 1168 non-authorized beds which were installed. The number of authorized beds
      per 10,000 inhabitants ranged from 16.1 (Picardie) to 33.2 (Corsica). Operations
      per 10,000 inhabitants ranged from 568 (Picardie) to 992 (Languedoc-Roussillon).
      The most frequent operations were adenoidectomies-amygdalectomies, cataract,
      appendectomy, herniacure, varicose veins of the lower limbs. Among the emergency
      operations, 91% of the operations were performed in 1156 permantly operating
      theaters. In these theaters, there was, on the average, one night operation every
      4 nights. Regional variations in the number of beds demonstrate the need for
      improvement in organization. For operations, migratory flow and age differences
      cannot explain all the differences observed. Medical management varies greatly
      suggesting that more rigorous methodology and clinical training are needed.

PMID- 9238804
TI  - [Control of hospital expenditures].
AB  - Hospital expenditures in France (300 billion francs in 1995) comprise half of the
      expenditures of the Health Care Assurance system. The government directive dated
      24 April 1996 created a national accreditation and evaluation agency. The
      effectiveness of the agency will largely depend on the ability of the experts to
      create a pragmatic system. The 5-year maximum delay for an accreditation request
      can be explained by the fact that the system is new, but will nevertheless delay
      hospital closure decisions and thus prolong the function of hospitals with
      reduced activity and thus less medical experience, leading to extra cost for the
      society. The directive also created regional hospitalization agencies which are
      to develop a regional health care policy, analyze and coordinate hospital
      activity and determine hospital resources. It is hoped that these agencies will
      be more effective than the former health care and social organization committees.
      The necessary decisions for hospital closures will be difficult due to the
      opposition of both the populations and elected officials. Finances for public
      facilities will continue on the basis of a global budget, an attempted macro
      economic cost-containment policy which has had only limited effect. For private
      facilities, use of medicalization data systems could have unfavorable effects if
      the data is too approximative and could cause undue increase in cost over benefit
      if the data is too exhaustive. The directive does not appear to modify the
      authorization system for major equipment expenditures. There is no mention of the
      increasing size of hospital administration staffs. Finally, the directive does
      not address the fundamental question of medical behavior: a modification of
      medical training which would place more emphasis on clinical training and
      reasoning.

PMID- 9238805
TI  - [Spinal cord astrocytomas and ependymomas: therapeutic strategy].
AB  - Ependymomas and astrocytomas are the most frequent spinal cord tumors. They have
      the same clinical expression and the only treatment is surgery. We report the
      experience of two neurochurgical teams working in Lyon and Brussels with 171
      operated patients, focusing on therapeutic strategies. Spinal cord ependymomas
      usually present as circumscribed benin tumors, complete exeresis is the best
      strategy. Long-term follow-up in 40 patients who were not given adjuvant
      radiotherapy showed no recurrence and satisfactory functional results.
      Astrocytomas are classically less well circumscribed but when exeresis is
      macroscopically complete, results are comparable with those of ependymomas as was
      found in 22 patients with long-term follow-up. Inversely, for infiltrating
      astrocytomas, pathology is usually malignant and prognosis is unfavorable despite
      radiotherapy or chemotherapy.

PMID- 9238806
TI  - [Spinal cord hemangioblastomas and pseudotumors: therapeutic strategy].

PMID- 9238807
TI  - [Laparoscopically extended hysterectomy for cervix cancer: technique, indications
      and results. Apropos of a series of 41 cases in Clermont].
AB  - We report a study of 41 radical hysterectomies performed through laparoscopic
      approach for carcinoma of the cervix uteri. According to the FIGO staging, the
      tumors were classified as 12 stages Ia2, 24 stages Ib, 4 stages IIa and 1 stage
      IIb. 17 patients were treated by exclusive surgical procedure. 24 patients
      received a combination of radiation therapy and surgery 2 patients had a tumor of
      the cervical stump after subtotal hysterectomy. The mean duration of the
      procedure was 270 minutes. The post-op stay was 6.5 days. There was no major
      operative and postoperative complication. Only one patient required a blood
      transfusion. The intravenous pyelogram control was correct in all cases. At this
      time, with a 4 to 76 months follow-up, no recurrence was observed. This
      experience suggests the faisability of the laparoscopic radical hysterectomy.
      This approach seems to be convenient in young and non obese women with a tumor
      less than 4 cm in the greatest diameter.

PMID- 9238808
TI  - [Axillary lymphadenectomy by lipo-aspiration and endoscopic picking. Apropos of
      72 cases].
AB  - Axillary lymphadenectomy is part of breast cancer treatment. It has two aims:
      prognosis and treatment. The high morbidity rate of conventional lymphadenectomy
      is unacceptable in conservative treatment of small tumors. Therefore we developed
      a new technique combining liposuction and endoscopic picking. So we are able to
      perform a conservative axillary lymphadenectomy with the same efficiency for
      prognosis and treatment with a near to zero morbidity. We report here our
      experience of 72 cases in endoscopic lymphadenectomy.

PMID- 9238809
TI  - [Peroperative manometric evaluation of posterior fundoplication by celioscopy].
AB  - The aim of this prospective study was to evaluate objectively the effects of a
      laparoscopic posterior fundoplication on the pressure and length of the lower
      oesophageal sphincter (LOS) and to compare these results to those of a group of
      patient who underwent the same technique through a laparotomy. Fourty six
      patients were included in the laparoscopic group and 48 in the open group.
      Intraoperative manometry was performed using the same material before and after
      the posterior fundoplication (after evacuating the pneumoperitoneum). Criteria of
      assessment were the increases in pressure and length of the LOS. The two groups
      were comparable regarding age, rate of hiatal hernia, and stage of the
      oesophagitis. In the laparoscopic group, the mean pressure of LOS (mmHg)
      increased from 10.1 +/- 3.8 to 35.2 +/- 12 after the fundoplication (that is 3.5
      times) and the length of LOS (cm) increased from 3.4 +/- 0.8 to 4.8 +/- 0.8 (that
      is 1.4 times). In the open group the increase was for the pressure and length
      respectively 3.3 times and 1.5 times the initial values. Thus by performing the
      same procedure we obtained the same effects on the pressure and length of the
      LOS. The effectiveness of laparoscopic posterior fundoplication should be similar
      to that of the open procedure.

PMID- 9238810
TI  - [Cavernous hemangioma of the rectum: an uncommon cause of pelvic pain. Apropos of
      2 cases].
AB  - Diffuse cavernous hoemangioma of the rectum is rare. Correct identification is
      often delayed. The patients usually present with rectal bleeding. We describe two
      men who had diffuse cavernous hoemangiomas. They complained of rectal pain. One
      appeared to have a rectal tumor and the other a levator syndrome.

PMID- 9238811
TI  - [Radiological evaluation of integration of bone grafts and bone substitutes after
      implantation to replace acetabular substance losses in reoperation of total hip
      prosthesis].
AB  - Plain radiograms are insufficient to evaluate the integrity of a graft used to
      replace acetabular tissue loss in reoperations for total hip replacement. The aim
      of this work was to compare radiographic, computed tomographic and magnetic
      resonance imaging findings. Two groups of patients including 12 hip joints in
      each were evaluated 5 years after undergoing reoperation for annular support.
      Allografts (5 cases) or xenografts (7 cases) were used in one group. Plain
      radiograms. CT-scan and MRI were performed in each patient. The graft-receiver
      bone borders were visible on the CT-scans but were not distinguishable on the
      radiograms. Bone and graft density and structure in contact with the implant
      could be determined on the CT-scan. MRI was difficult to interpret in most cases
      due to implant-induced artefacts and is not recommended in this type of
      reconstruction.

PMID- 9238812
TI  - [Epidemiology and genetics of cancers of the ovary].
AB  - 5% of ovarian cancers occur in a hereditary predisposition context. Clinical
      syndromes are defined by 3 or more cases of breast or ovarian cancers, or cancers
      from the Lynch-type II spectrum (colon, endometrium...) in one family branch.
      When the diagnosis is established, genetic counselling is provided to the
      kindred, a molecular diagnosis is undertaken for BRCA1 and BRCA2 genes, screening
      for ovarian and other at risk cancers is proposed, or prophylactic oophorectomy
      is proposed for at least 35 years old women without children conception projects.

PMID- 9238813
TI  - [Pathological anatomy and cellular biology of cancers of the ovary].
AB  - Four tumor types are considered in current classifications of ovarian tumors:
      epithelial tumors, stromal and sex cord tumors, germ cell tumors, and secondary
      tumors. Epithelial tumors represent 85% of ovarian tumors. They are classified as
      benign, of borderline malignancy or malignant. In this group, serious tumors are
      the most frequently observed tumors. Dynamic approach of ovarian tumors allows to
      assess the question of the monoclonality of these tumors, to study their
      stimulation by growth factors, to study their spread and their potential of
      tissue invasion, and finally to study the factors of response to treatment.

PMID- 9238814
TI  - [Diagnosis of cancers of the ovary].
AB  - Early diagnosis of ovarian cancer is difficult and is still a matter of chance.
      Diagnosis rests on pelvic examination, ultrasonography and serum CA125 levels.
      Surgery establishes a definitive diagnosis and allows accurate staging and
      primary cytoreduction. No technique suitable for routine screening is currently
      available.

PMID- 9238815
TI  - [Surgery of primary cancers of the ovary].
AB  - Surgery plays a key role in the management of ovarian cancers. Primary
      intervention should confirm the diagnosis, establish a precise staging of the
      disease and a maximally debulking of any extra-ovarian deposit. This primary
      operation must be done by a surgeon expert in this surgery to avoid morbidity,
      and lost of chance to becure for the patient. Second look operation is still
      subject of controversies for non epithelial cancer, surgical options are also
      discussed.

PMID- 9238816
TI  - [First line chemotherapy of epithelial cancers of the ovary].
AB  - Treatment of epithelial ovarian cancer is based mainly on surgery and
      chemotherapy. Indications of chemotherapy depends on stage of disease and tumor
      histology. Initial polychemotherapy must be a platinum compound based regimen
      with respect of dose-intensity. Up to now the initial standard chemotherapy is a
      cyclophosphamide and platinum combination. Only one randomized study comparing
      cisplatin-cyclophosphamide and cisplatin-Taxol has been published in patients
      with macroscopic residual disease (> 1 cm). The improvement of survival with
      Taxol has led to propose this association as standard treatment in the USA and in
      some European countries. The place and role of anthracyclines are discussed. New
      drugs (topotecan, Oxaliplatine) and new modalities of administration
      (intensification, intraperitoneal route) are currently under evaluation.

PMID- 9238817
TI  - [Follow-up of treated cancers of the ovary].
AB  - The main goal of the follow up in ovarian cancer is to achieve an early detection
      of recurrence after a complete remission or to assess the antitumoral efficiency
      of the treatment used. When the tumoral antigen CA125 is expressed by the primary
      tumor, the most sensitive test is the sequentially evaluation of the CA125 in the
      blood. An increasing slope of the serous CA125 is related to disease progression
      which must be confirmed by imaging techniques including immunoscintigraphy.

PMID- 9238818
TI  - [Second line treatments of cancers of the ovary].
AB  - Ovarian adenocarcinomas are among the most chemosensitive tumors. Platinum
      derivatives are the most efficient agents. The role of the second-line therapy is
      either to treat the relapse (salvage therapy), or to prevent it (consolidation
      therapy). The most active agents in the salvage setting are new molecules:
      taxoids, vinorelbin, topotecan. Classical agents such as hexamethylmelamine or
      epirubicin are still worth of use. Reintroduction of platinum derivatives
      (oxaliplatin) and associations combining new and classical cytostatic agents are
      still on study. Consolidation treatment may use platinum-based intraperitoneal
      chemotherapy, and most promising results have been achieved with high-dose
      alkylating chemotherapy followed by haematopoietic stem-cell reinjection.

PMID- 9238819
TI  - [Acute myeloblastic leukemia. Diagnosis, course].

PMID- 9238820
TI  - [Medical consumption. Different positions and determining factors].

PMID- 9238821
TI  - [Indications of chromosome and DNA analysis for the diagnosis of genetic
      diseases].

PMID- 9238822
TI  - [Iatrogenic affections linked to the use of drugs and current use of equipment.
      Main causes, favouring circumstance, prevention].

PMID- 9238823
TI  - [Acute delusion state. Diagnostic orientation, treatment and management in
      emergency].

PMID- 9238824
TI  - [Arterial hypertension in pregnancy. Diagnosis, complications, treatment].

PMID- 9238825
TI  - Anterior cervical osteophytes: a rare cause of dysphagia.
AB  - Anterior cervical osteophyte is a rare cause of dysphagia usually occurring in
      the elderly. We report two cases in which the anterior cervical osteophytes
      impinged upon the esophagus, and we describe their surgical management. Initial
      investigation of a case of dysphagia should be directed to the common causes;
      however, in the elderly and in those with disorders of the cervical spine an
      anterior cervical osteophyte may be the cause of dysphagia.

PMID- 9238826
TI  - Preoperative pulmonary function tests do not predict outcome after coronary
      artery bypass.
AB  - PURPOSE: To evaluate the utility of preoperative pulmonary function tests in
      predicting postoperative complications and lengths of stay after coronary artery
      bypass grafting. METHODS: Medical records of 193 consecutive patients who
      underwent coronary artery bypass grafting from October 1993 to September 1994
      were reviewed. Preoperative pulmonary function tests, comorbid conditions,
      smoking history, postoperative complications, and total days in the intensive
      care unit, hospital, and on mechanical ventilation were abstracted. Data were
      analyzed using linear regressions, analyses of variance, and nonpaired Student's
      t tests. RESULTS: Pulmonary function tests were normal in 56 subjects (29%, group
      1), mildly impaired in 72 (37%, group 2), and moderately impaired in 35 (18%,
      group 3). Thirty patients (16%) had no pulmonary function tests. Group 3 subjects
      were older (71) compared to groups 1 and 2 (63 and 65, P < 0.05). There was no
      major difference in comorbid conditions or smoking status among the groups. All
      patients had atelectasis postoperatively. The most frequent postoperative
      complications were pleural effusions (43%), pulmonary edema or congestive heart
      failure (28%), and atrial fibrillation (35%). The repeat surgery rate was 3.6%.
      The mean length of hospital stay was 10.1 +/- 0.6 days, with 1.5 +/- 0.1 days of
      mechanical ventilation and 2.8 +/- 0.2 days of intensive care unit stay. Overall,
      pulmonary function tests had no predictive value for postoperative pulmonary and
      nonpulmonary complications, nor for durations of mechanical ventilation and
      intensive care unit stay. There was a trend toward increased length of hospital
      stay in patients with impaired pulmonary function tests (group 18.6 +/- 0.6,
      group 2 9.6 +/- 0.8, group 312.7 +/- 2.3 days, P = 0.09) but this was consistent
      with random variation. CONCLUSIONS: Preoperative pulmonary function tests were
      not useful in predicting postoperative outcomes in patients undergoing coronary
      artery bypass grafting.

PMID- 9238828
TI  - Carpal tunnel syndrome: the significance of electrodiagnostic testing.

PMID- 9238829
TI  - Anesthesia is not dreamland.

PMID- 9238827
TI  - Life threatening pulmonary embolus in a factor V Leiden carrier on oral
      contraceptives: a case report.
AB  - Venous thromboembolism is a serious, potentially lethal health problem affecting
      one per 1,000 people annually. Major surgery, the use of oral contraceptives,
      complicated pregnancy, fractures, and immobilization increase the risk of
      thrombosis. In addition to these factors, thrombosis is associated with inherited
      deficiencies of antithrombin III, protein C, and protein S. Together these do not
      account for more than five to 10% of the cases. Hereditary activated protein C
      resistance has been recognized as a basis for a majority of cases of familial
      thrombosis. It accounted for more than a 10 times higher number than that of
      other known genetic defects. We describe a case of a young female who presented
      with a pulmonary embolism and was discovered to have activated protein C
      resistance. This patient had a heterozygous mutation for factor V Leiden and was
      taking oral contraceptives. This report underlines: 1) increased risk of venous
      thrombosis in oral contraceptive users who carry factor V Leiden mutation
      associated with functional resistance to the normal anticoagulation activities of
      protein C; 2) most episodes occurring in the young are minor, but pulmonary
      embolus can occur; 3) the importance of identifying other affected members of the
      family; and 4) the importance of anticoagulation prophylaxis at times of enhanced
      risk, particularly during pregnancy, postpartum, and major surgery.

PMID- 9238830
TI  - Distinctions between adult and paediatric AIDS.

PMID- 9238831
TI  - Fc epsilon RI-expressing antigen-presenting cells: new players in the atopic
      game.

PMID- 9238832
TI  - CSF-I signal transduction: what is of functional significance?

PMID- 9238833
TI  - Beta-endorphin in the immune system: a role at last?

PMID- 9238834
TI  - Seeing the wood for the trees: the forgotten role of neutrophils in rheumatoid
      arthritis.

PMID- 9238835
TI  - Common variable immunodeficiency: how many diseases?

PMID- 9238836
TI  - Molecules and mechanisms operating in septic shock: lessons from knockout mice.

PMID- 9238837
TI  - Oral tolerance: immune mechanisms and treatment of autoimmune diseases.

PMID- 9238838
TI  - Production of cytokines by human B cells in health and disease.

PMID- 9238839
TI  - Thymic dendritic cells.

PMID- 9238840
TI  - Chemical events in signal transduction.

PMID- 9238841
TI  - Respect: its meaning and measurement as an element of patient care.
AB  - The purpose of this article is to suggest systematic observation of provider
      patient interactions as part of the evaluation of the quality of patient care
      provided in managed-care settings. There have been many calls for the inclusion
      of patient satisfaction measures in outcome evaluations. Patient satisfaction is
      very important since it relates to appropriate service utilization, yet the
      measurement of patient satisfaction is not enough. An example of systematic
      observation, the "Clinic Observation Record" (COR), was used by trained observers
      in an early evaluation of federally-funded family planning clinics, along with a
      measure of patient satisfaction (PATSAT). Including time spent in the clinic,
      which was important but played a relatively minor role, the COR (in a regression
      analysis) accounted for 36% of the variance in the PATSAT score for patients in
      34 clinics. Personal interactions with the doctor and nurse were the most
      important elements contributing to patient satisfaction. Improvements in the ways
      patients were addressed, introduced to staff, and treated, as well as in the
      clinic environment, were needed in many of the clinics observed.

PMID- 9238842
TI  - Compliance with the recommendations of the Institute of medicine report, The
      Future of Public Health: a survey of local health departments.
AB  - In 1989 a survey of state health officials was conducted to ascertain the extent
      that the recommendations of the 1988 Institute of Medicine's report, The Future
      of Public Health, were in place. We applied a similar survey in 1996 to assess
      the level of implementation of the IOM recommendations at the local health
      department level. Agreement with the specific IOM recommendations at the local
      level was, in almost all cases, greater than 90%. However, when one views the
      extent of these recommendations in place, nearly half fall below 50%. While there
      have been improvements in areas such as education of the public and outreach
      towards legislators and voluntary health organizations, our results show that
      there are still major short-comings when it comes to implementing the
      recommendations. Lack of resources at the local level appears to be the
      predominant cause of the low level of implementation, with restricted authority
      and lack of support also contributing to the problem. We feel the IOM
      recommendations can provide a strong foundation for our public health system, and
      hope these results help serve as a benchmark for further study.

PMID- 9238843
TI  - Fighting tuberculosis in the 1990s: how effective is planning in policy making?
AB  - Planning is a common tool for addressing important health issues, especially
      urgent ones, and has been reintroduced recently in several federal, state, and
      local public health programs. This article presents a case study of planning and
      policy making concerning the reemergence of tuberculosis in urban areas, using
      Washington, D.C. and New York City as examples. Planning was unsuccessful in D.C.
      because it failed to acknowledge the important political and bureaucratic aspects
      of policy making. In New York City, on the other hand, planning played a central
      role in policy-making efforts, and the health department took a leadership role
      in building a consensus on the problem, formulating strategies, and overcoming
      implementation obstacles. This article concludes with several key considerations
      for making planning more effective in health policy-making.

PMID- 9238844
TI  - Washington State reorganization: more of the story.
AB  - The creation of a new Department of Health in Washington State in 1989 provided
      an opportunity for analysis of the many forces beyond the pressure of interest
      groups leading to such a change. Interviews with key actors from executive and
      legislative branches of state government, local government, and interested health
      organizations were conducted to uncover the full scope considered for the new
      department, and the interactions that led to the final, narrower entity. A
      process model based on these findings is presented as a useful tool for those
      seeking to improve public health at the state level through changes in the
      organizational units responsible for health activities.

PMID- 9238845
TI  - A ten year review of the iodine deficiency disorders program of the People's
      Republic of China.
AB  - This paper reviews the Iodine Deficiency Disorders (IDD) Elimination Program of
      the People's Republic of China (PRC). Over 700 million people live in iodine
      deficient regions of China and the social and economic consequences of IDD are
      profound. National and international organisations have supported China's
      advocacy, social mobilisation and health education programs. Many countries
      affected by IDD have benefited from discoveries emerging from China's aggressive
      and effective multisectoral approach to this massive public health problem. The
      challenge of the next decade is to sustain the momentum through the use of cost
      effective monitoring and quality improvement strategies, particularly, in those
      regions in which a large proportion of babies continue to be at risk of brain
      damage due to iodine deficiency. This paper sets China's IDD Program in an
      international context by reference to the literature and through consultation
      with public health experts.

PMID- 9238846
TI  - Neurosteroids: of the nervous system, by the nervous system, for the nervous
      system.
AB  - Neurosteroids are synthesized in the central and peripheral nervous system,
      particularly but not exclusively in myelinating glial cells, from cholesterol or
      steroidal precursors imported from peripheral sources. They include 3 beta
      hydroxy-delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone
      (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative
      of progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha,5 alpha-THPROG).
      These compounds can act as allosteric modulators of neurotransmitter receptors,
      such as GABAA, NMDA, and sigma receptors. Progesterone (PROG) is also a
      neurosteroid, and a progesterone receptor (PROG-R) has been identified in
      peripheral and central glial cells. At different places in the brain,
      neurosteroid concentrations vary according to environmental and behavioral
      circumstances, such as stress, sex recognition, or aggressiveness. A
      physiological function of neurosteroids in the central nervous system is strongly
      suggested by the role of hippocampal PREGS with respect to memory, observed in
      aging rats. In the peripheral nervous system, a role for PROG synthesized in
      Schwann cells has been demonstrated in the repair of myelin after cryolesion of
      the sciatic nerve in vivo and in cultures of dorsal root ganglia neurites. It may
      be important to study the effect of abnormal neurosteroid
      concentrations/metabolism with a view to the possible treatment of functional and
      trophic disturbances of the nervous system.

PMID- 9238847
TI  - Estrogen: nontranscriptional signaling pathway.
AB  - The long-term, genomic actions of estrogen and other steroid hormones are now
      relatively well understood. In this process, steroids bind to a
      cytoplasmic/nuclear receptor and the hormone receptor complex that, in turn,
      binds to DNA and triggers RNA-dependent protein synthesis. This process produces
      a response over time periods of several minutes to hours to days. Estrogen also
      exerts a variety of short-term effects (observed in milliseconds to minutes) on
      target organs that are not compatible with the classical genomic mechanism. These
      short-term, nontranscriptional actions are thought to be neuromodulatory in
      nature and critical for cell-cell communication. This chapter discusses current
      evidence for nontranscriptional effects of estrogen, with major emphasis on
      electrophysiological results demonstrating rapid, estrogen-induced changes in
      neuronal excitability. The mechanisms for nontranscriptional estrogen effects are
      also considered. These mechanisms include nonspecific influences on the lipid
      bilayer, specific binding to novel membrane receptors, direct modulation of
      neurotransmitter-ion channel complexes, and direct activation of second messenger
      systems. Particular attention will be focused on studies from our laboratory
      investigating mechanisms of estrogenic potentiation of kainate-induced currents
      in hippocampal neurons. Finally, the physiological relevance of short-term
      estrogenic actions will be addressed.

PMID- 9238848
TI  - Nongenomic actions of steroids on gonadotropin release.
AB  - The release of gonadotropins is effected by GnRH and regulated by steroids. The
      classical mechanism of steroid hormone action, which implies the binding of
      hormone receptor complexes to regulatory elements of nuclear genes, is derived
      largely from the well-studied and familiar steroids such as progesterone,
      testosterone, and estradiol. Their effects on gonadotropin release generally have
      been examined following hours or days of exposure and therefore cannot account
      for the rapid effects of steroids on gonadotropin release. Moreover, tissues such
      as gonad, pituitary, and hypothalamus can produce a variety of hormonally active
      steroids in addition to these well-studied, traditional ones. The recently
      discovered allylic steroid, 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP), is
      readily interconverted from/to progesterone and is found at appreciable levels in
      serum, gonads, pituitary, hypothalamus, and other tissues. 3 alpha HP has
      provided the "missing link" in the progesterone biosynthetic/ metabolic pathways,
      allowing cyclical 4-pregnene and 5 alpha-pregnane pathways to be described for
      steroidogenic tissues. Among the functions ascribed to 3 alpha HP is the ability
      to selectively and rapidly (within seconds or minutes) suppress GnRH-provoked FSH
      release. In vitro studies using pituitary gonadotropes in culture and in
      perifusion paradigms suggest that suppression of FSH release by 3 alpha HP occurs
      as a result of nongenomic mechanisms of action. These mechanisms are discussed
      and include interaction at the level of receptors in the gonadotrope membrane and
      the cell-signaling pathway involving protein kinase C, phospholipase C, or IP3
      induced Ca2+ mobilization and Ca2+ channels. This may be the first evidence of a
      gonadal steroid regulating gonadotropin release by nongenomic mechanisms of
      action. In order to understand the critical role of steroids in the rapid
      regulation of secretory (and bence, circulating) levels of gonadotropins, other
      gonadal steroids will need to be examined for their nongenomic action on
      gonadotropes.

PMID- 9238849
TI  - The multifunctional role of the co-activator CBP in transcriptional regulation.
AB  - One of the most studied and best-understood examples of second messenger
      regulated gene transcription involves the activation of genes by the cyclic AMP
      pathway: stimulation of several hormone, growth factor, and neurotransmitter
      receptors activates adenylyl cyclase, generating cyclic AMP that, by binding to
      the regulatory subunit of protein kinase A (PKA), dissociates the PKA catalytic
      subunit. The free catalytic subunit is transported to the nucleus where it
      phosphorylates and consequently activates the transcription factor CREB. This
      phosphorylation of CREB allows interaction with the co-activator CBP, which binds
      to components of the basal transcriptional machinery. CBP and its homologue p300
      are targets for several viral-transforming proteins, implying that these co
      activators have a more extensive role in cellular function. Indeed, recent
      studies have demonstrated that multiple transcription factors bind to CBP,
      including c-jun, c-myb, MyoD, E2F1, YY1, and members of the steroid hormone
      receptor superfamily, although it is not yet clear which of these transcription
      factors depend upon CBP for function. Determining exactly which transcriptional
      pathways require CBP in vivo and which genes are activated by CBP will provide an
      important clue in developmental regulation and cell cycle control, since
      mutations in the human CBP gene have been found to cause developmental
      abnormalities and a predisposition for some types of cancer. In this review, we
      will discuss the mechanisms involved in the PKA-dependent activation of CREB and
      describe how the co-activator CBP and its homologue are involved in this process.
      In addition, we will outline the various transcription factor pathways that CBP
      has been proposed to activate. Finally, we will discuss the possible role of CBP
      in cellular transformation and differentiation.

PMID- 9238850
TI  - Coupling signalling pathways to transcriptional control: nuclear factors
      responsive to cAMP.
AB  - Several endocrine and neuronal functions are governed by the cAMP-dependent
      signalling pathway. In eukaryotes, transcriptional regulation upon stimulation of
      the adenylyl cyclase signalling pathway is mediated by a family of cAMP
      responsive nuclear factors. This family consists of a large number of members
      that may act as activators or repressors. These factors contain the basic domain/
      leucine zipper motifs and bind as dimers to cAMP-response elements (CRE). The
      function of CRE-binding proteins (CREBs) is modulated by phosphorylation by
      several kinases. Direct activation of gene expression by CREB requires
      phosphorylation by the cAMP-dependent protein kinase A to the serine-133 residue.
      Among the repressors, ICER (Inducible cAMP Early Repressor) deserves special
      mention. ICER is generated from an alternative CREM promoter and constitutes the
      only inducible cAMP-responsive element binding protein. Furthermore, ICER
      negatively autoregulates the alternative promoter, thus generating a feedback
      loop. In contrast to the other members of the CRE-binding protein family, ICER
      expression is tissue specific and developmentally regulated. The kinetics of ICER
      expression are characteristic of an early response gene. Our results indicate
      that CREM plays a key physiological and developmental role within the
      hypothalamic-pituitary-gonadal axis. We have previously shown that the
      transcriptional activator CREM is highly expressed in postmeiotic cells.
      Spermiogenesis is a complex process by which postmeiotic male germ cells
      differentiate into mature spermatozoa. This process involves remarkable
      structural and biochemical changes that are under the hormonal control of the
      hypothalamic-pituitary axis. We have addressed the specific role of CREM in
      spermiogenesis using CREM-mutant mice generated by homologous recombination.
      Analysis of the seminiferous epithelium from mutant male mice reveals that
      spermatogenesis stops at the first step of spermiogenesis. Late spermatids are
      completely absent, while there is a significant increase in apoptotic germ cells.
      A series of postmeiotic germ cell-specific genes are not expressed. Mutant male
      mice completely lack spermatozoa. This phenotype is reminiscent of cases of human
      infertility. We have shown that ICER is regulated in a circadian manner in the
      pineal gland, the site of the hormone melatonin production. This night-day
      oscillation is driven by the endogenous clock (located in the suprachiasmatic
      nucleus, SCN). The synthesis of melatonin is regulated by a rate-limiting enzyme,
      the serotonin N-acetyltransferase (NAT). By using the CREM-deficient mice and by
      analysis of the regulatory region of the gene encoding the serotonin NAT, we have
      established that ICER is responsible for the amplitude and rhythmicity of NAT and
      thus for the oscillation in the hormonal synthesis of melatonin.

PMID- 9238851
TI  - Role of co-activators and co-repressors in the mechanism of steroid/thyroid
      receptor action.
AB  - Steroid/thyroid hormone receptors are ligand-dependent transcription factors that
      regulate diverse aspects of growth, development, and homeostasis by binding as
      homodimers or heterodimers to their cognate DNA response elements to modulate
      transcription of target genes. Transactivation by steroid/ thyroid hormone
      receptors involves a conserved AF-2 domain located in the distal carboxy-terminus
      of the receptors. The existence of co-factors, termed co-activators or adapters,
      was first suggested by transcriptional squelching between progesterone receptors
      and estrogen receptors. Co-repressors were also postulated to contribute to the
      silencing function of unliganded thyroid hormone receptor (TR). The yeast two
      hybrid system and Far-Western blotting have been used to identify several
      proteins that interact with members of the steroid/thyroid hormone receptor
      superfamily in a ligand-sensitive manner. Our laboratory cloned the first
      functional co-activator, termed steroid receptor co-activator-one (SRC-1), that
      appears to be a general co-activator for all steroid receptors tested and
      enhances transactivation of steroid hormone-dependent target genes. Subsequently,
      many more putative co-activators have been reported, including the SRC-1 related
      proteins, TIF2 and GRIP1, and other putative and unrelated co-activators such as
      ARA70, Trip1, RIP140, and TIF1. In addition, another co-activator, CREB-binding
      protein (CBP), has been shown to enhance steroid receptor-dependent target gene
      transcription. CBP and SRC-1 interact and synergistically enhance transcriptional
      activation by the ER and PR. Therefore, a ternary complex-consisting of CBP, SRC
      1, and liganded steroid receptors-may form to increase the rate of hormone
      responsive gene transcription. Similarly, co-repressors, such as SMRT and N-CoR,
      for TR and retinoic acid receptors (RAR) have been identified. The unliganded TR
      and RAR have been shown to inhibit basal promoter activity; this silencing of
      target gene transcription by unliganded receptors is mediated by these co
      repressors. Collectively, available evidence supports the following model of
      steroid-responsive gene transcription. Upon binding of agonist the receptor
      changes its conformation in the ligand-binding domain that enables recruitment of
      co-activators, which allows the receptor to interact with the basal
      transcriptional machinery more efficiently and to activate transcription. In
      contrast, binding of antagonists induces a different conformational change in the
      receptor. Although some antagonist-bound receptor can dimerize and bind to its
      cognate DNA element, it fails to dislodge the associated co-repressors, which
      results in a nonproductive interaction with the basal transcriptional machinery.
      Similarly, the TR and RAR associate with co-repressors in the absence of ligand,
      thereby resulting in a negative interaction with the transcriptional machinery
      that silences target gene expression. In the case of mixed agonist/antagonists,
      such as 4-hydroxytamoxifen, activation of gene transcription may depend on the
      relative ratio of co-activators and co-repressors in the cell or cell-specific
      factors that determine the relative agonistic or antagonistic potential of
      different compounds. These co-activators and co-repressors appear to act as an
      accelerator and/or a brake that modulates transcriptional regulation of hormone
      responsive target gene expression. Thus, the recent discovery of co-activators
      and co-repressors expands our knowledge of the mechanisms of steroid receptor
      action.

PMID- 9238852
TI  - Steroidogenic factor 1 plays multiple roles in endocrine development and
      function.
AB  - The nuclear hormone receptor family comprises a group of structurally related
      transcriptional regulators that mediate the actions of diverse ligands, including
      steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor
      family also contains members for which activating ligands have not been
      identified-the orphan nuclear receptors. One of these orphan nuclear receptors,
      steroidogenic factor 1 (SF-1), has emerged as an essential regulator of
      steroidogenic cell function within the adrenal cortex and gonads; SF-1 also plays
      important roles in reproduction at all three levels of the hypothalamic-pituitary
      gonadal axis. First identified as a tissue-specific regulator of the
      transcription of the cytochrome P450 steroid hydroxylases, considerably broader
      roles for SF-1 were revealed by genetic studies in mice lacking SF-1 due to
      targeted gene disruption. These SF-1-knockout mice had agenesis of their adrenal
      glands and gonads, male-to-female sex reversal of their internal and external
      genitalia, impaired gonadotrope function, and agenesis of the ventromedial
      hypothalamic nucleus. These studies delineated essential roles of SF-1 in
      regulating endocrine differentiation and function at multiple levels. Despite
      these insights into roles of SF-1, the precise mechanisms by which SF-1 exerts
      its multiple effects remain to be determined. This review highlights experiments
      that have established SF-1 as a pivotal determinant of endocrine differentiation
      and function and identifies areas in which additional studies are needed to
      expand our understanding of SF-1 action.

PMID- 9238853
TI  - Aromatase expression in health and disease.
AB  - Family 19 of the P450 superfamily is responsible for the conversion of C19
      androgenic steroids to the corresponding estrogens, a reaction known as
      aromatization, since it involves conversion of the delta 4-3-one A-ring of the
      androgens to the corresponding phenolic A-ring characteristic of estrogens. Its
      members occur throughout the entire vertebrate phylum. The reaction mechanism of
      aromatase is very interesting from a chemical point of view and has been studied
      extensively; however, a detailed examination of structure-function relationships
      has not been possible due to lack of a crystal structure. Recent attempts to
      model the three-dimensional structure of aromatase have permitted a model that
      accounts for the reaction mechanism and predicts the location of aromatase
      inhibitors. The gene encoding human aromatase has been cloned and characterized
      and shown to be unusual compared to genes encoding other P450 enzymes, since
      there are a number of untranslated first exons that occur in aromatase
      transcripts in a tissue-specific fashion, due to differential splicing as a
      consequence of the use of tissue-specific promoters. Thus, expression in ovary
      utilizes a proximal promoter that is regulated primarily by cAMP. On the other
      hand, expression in placenta utilizes a distal promoter that is located at least
      40 kb upstream of the start of transcription and that is regulated by retinoids.
      Other promoters are employed in brain and adipose tissue. In the latter case,
      class I cytokines such as IL-6 and IL-11 as well as TNF alpha are important
      regulatory factors. PGE2 is also an important regulator of aromatase expression
      in adipose mesenchymal cells via cAMP and PGE2 appears to be a major factor
      produced by breast tumors that stimulates estrogen biosynthesis in local
      mesenchymal sites. In all of the splicing events involved in the use of these
      various promoters, a common 3'-splice junction is employed that is located
      upstream of the start of translation; thus, the coding regions of the transcripts
      and hence the protein-are identical regardless of the tissue site of expression;
      what differ in a tissue-specific fashion are the 5'-ends of the transcripts. This
      pattern of expression has great significance both from a phylogenetic and
      ontogenetic standpoint as well as for the physiology and pathophysiology of
      estrogen formation. Recently, a number of mutations of the aromatase gene have
      been described, which give rise to complete estrogen deficiency. In females this
      results in virilization in utero and primary amenorrhea with hypergonadotropic
      hypogonadism at the time of puberty. In men the most striking feature is
      continued linear bone growth beyond the time of puberty, delayed bone age, and
      failure of epiphyseal closure, thus indicating an important role of estrogens in
      bone metabolism in men. In both sexes the symptoms can be alleviated by estrogen
      administration.

PMID- 9238854
TI  - Growth hormone-releasing hormone and growth hormone-releasing peptide as
      therapeutic agents to enhance growth hormone secretion in disease and aging.
AB  - Growth hormone (GH) secretion is pulsatile and is tightly regulated. In this
      chapter the effects of aging, nutrition, the feedback effects of IGF-I, and the
      role of body composition in the decline of GH secretion will be discussed. In GH
      deficient adults there is an increase in the amount of intra-abdominal (visceral)
      fat. Similarly, with increasing age, there is an increase in visceral fat and
      there is a tight correlation between 24-hour GH release and visceral fat in the
      elderly. This may have serious metabolic consequences, including insulin
      resistance and increased cardiovascular risk. There are at least four potential
      mechanisms for the age-related decline in GH secretion: 1) decreased release of
      growth hormone releasing-hormone (GHRH); 2) increased release of somatostatin; 3)
      enhanced sensitivity to IGF-I feedback; and 4) decreased somatotroph mass. The
      latter two potential mechanisms are discussed. There is little evidence that
      there is any change in sensitivity to IGF-I feedback with aging and the
      somatotroph cell mass appears to be preserved in older subjects. The GH axis may
      be stimulated by either GHRH or by growth hormone-releasing peptide (GHRP) and
      related compounds. Chronic therapy with GHRH in GH-deficient children restores GH
      secretion and accelerates linear growth. Mutations of the GHRH receptor lead to
      GH deficiency and short stature. This indicates the essential role of GHRH in
      regulation of GH secretion. Growth hormone releasing peptide was discovered in
      1981. Recently, the GHRP/GH secretagogue receptor has been cloned and orally
      active GHRP mimetics have been developed. One such compound, MK-677, stimulates
      pulsatile GH secretion and its effects persist for 24 hours. Oral administration
      of MK-677 for a month in the elderly demonstrates that this route stimulates a
      physiologic pattern of GH secretion. The amplitude of the GH pulses was increased
      but the number of GH pulses was unchanged. Thus, in older individuals, the amount
      of GH secreted in 24 hours is restored toward that seen in young adults. This
      compound also enhances GH secretion in GH-deficient adults who had been GH
      deficient during childhood. The development of stable, orally active molecules to
      stimulate the GHRP/GH secretagogue receptor is a practical reality. These GH
      secretagogues may have a therapeutic role in short stature and adult GH
      deficiency. In addition, the use of GH secretagogues in normal aging merits
      investigation, as growth hormone may regulate body composition in older adults.

PMID- 9238855
TI  - Mineralocorticoid receptors, salt, and hypertension.
AB  - This review, covering work from the Baker Institute and elsewhere, is divided
      into four sections. In the first a summary account of two areas-mineralocorticoid
      receptors and the enzyme 11 beta hyderoxysteroid dehydrogenase-will be given as
      background. Next is a brief consideration of the three single-gene causes of
      human hypertension described to date-glucocorticoid-remediable aldosteronism.
      Liddle's syndrome, and apparent mineralocorticoid excess-in all of which abnormal
      sodium handling is a feature. Third, the sequelae of aldosterone occupancy of
      nonepithelial mineralocorticoid receptors will be analyzed in some detail by
      reviewing studies on experimental mineralocorticoid hypertension and cardiac
      fibrosis from this laboratory and elsewhere. Finally, three recent studies from
      this laboratory will be presented: on putative 11-ketosteroid receptors in
      epithelial tissue, on glucose-PKC potentiation of mineralocorticoid effects on
      heart cells, and on the necessity for factors/ processes other than the
      conversion of cortisol to cortisone (or, in the rat, corticosterone to 11
      dehydrocorticosterone) to ensure aldosterone-specific effects in
      mineralocorticoid target tissues.

PMID- 9238856
TI  - Mutations contributing to human blood pressure variation.
AB  - In spite of a large body of physiological, biochemical, and recently genetic
      investigations, the causes of hypertension remain largely unknown. Recognition
      that hypertension is, in part, genetically determined has motivated studies to
      identify mutations conferring susceptibility. To date, mutations in at least 10
      genes have been shown to alter blood pressure. The majority are rare mutations
      responsible for various mendelian hyper- and hypotensive syndromes, imparting
      large quantitative effects. Those causing hypertension are glucocorticoid
      remediable aldosteronism, the syndrome of apparent mineralocorticoid excess, and
      Liddle's syndrome. Conversely, pseudohypoaldosteronism type 1, Bartter's, and
      Gitelman's syndromes all cause hypotension. In addition, mutations in the
      angiotensinogen gene are associated with hypertension. All these mutations alter
      blood pressure through a common pathway, affecting salt and water reabsorption in
      the kidney. These findings demonstrate the place of molecular genetic approaches
      in elucidating the underlying determinants of human blood pressure variation and
      may provide insight into the physiological mechanisms underlying common forms of
      hypertension.

PMID- 9238857
TI  - Aging of the female reproductive system: a window into brain aging.
AB  - The menopause marks the permanent end of fertility in women. It was once thought
      that the exhaustion of ovarian follicles was the single, most important
      explanation for the transition to the menopause. Over the past decade, this
      perception has gradually changed with the realization that there are multiple
      pacemakers of reproductive senescence. We will present evidence that lends
      credence to the hypothesis that the central nervous system is a critical
      pacemaker of reproductive aging and that changes at this level contribute to the
      timing of the menopause. Studies demonstrate that an increasing de
      synchronization of the temporal order of neuroendocrine signals may contribute to
      the accelerated rate of follicular loss that occurs during middle age. We suggest
      that the dampening and destabilization of the precisely orchestrated ultradian,
      circadian, and infradian neural signals lead to miscommunication between the
      brain and the pituitary-ovarian axis. This constellation of hypothalamic
      pituitary-ovarian events leads to the inexorable decline of regular cyclicity and
      heralds menopausal transition.

PMID- 9238858
TI  - The melatonin rhythm-generating enzyme: molecular regulation of serotonin N
      acetyltransferase in the pineal gland.
AB  - A remarkably constant feature of vertebrate physiology is a daily rhythm of
      melatonin in the circulation, which serves as the hormonal signal of the daily
      light/dark cycle: melatonin levels are always elevated at night. The biochemical
      basis of this hormonal rhythm is one of the enzymes involved in melatonin
      synthesis in the pineal gland-the melatonin rhythm-generating enzyme-serotonin N
      acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, E.C. 2.3.1.87). In
      all vertebrates, enzyme activity is high at night. This reflects the influences
      of internal circadian clocks and of light. The dynamics of this enzyme are
      remarkable. The magnitude of the nocturnal increase in enzyme activity ranges
      from 7- to 150-fold on a species-to-species basis among vertebrates. In all cases
      the nocturnal levels of AA-NAT activity decrease very rapidly following exposure
      to light. A major advance in the study of the molecular basis of these changes
      was the cloning of cDNA encoding the enzyme. This has resulted in rapid progress
      in our understanding of the biology and structure of AA-NAT and how it is
      regulated. Several constant features of this enzyme have become apparent,
      including structural features, tissue distribution, and a close association of
      enzyme activity and protein. However, some remarkable differences among species
      in the molecular mechanisms involved in regulating the enzyme have been
      discovered. In sheep, AA-NAT mRNA levels show relatively little change over a 24
      hour period and changes in AA-NAT activity are primarily regulated at the protein
      level. In the rat, AA-NAT is also regulated at a protein level; however, in
      addition, AA-NAT mRNA levels exhibit a 150-fold rhythm, which reflects cyclic AMP
      dependent regulation of expression of the AA-NAT gene. In the chicken, cyclic AMP
      acts primarily at the protein level and a rhythm in AA-NAT mRNA is driven by a
      noncyclic AMP-dependent mechanism linked to the clock within the pineal gland.
      Finally, in the trout, AA-NAT mRNA levels show little change and activity is
      regulated by light acting directly on the pineal gland. The variety of mechanisms
      that have evolved among vertebrates to achieve the same goal-a rhythm in
      melatonin-underlines the important role melatonin plays as the hormonal signal of
      environmental lighting in vertebrates.

PMID- 9238859
TI  - New concepts in extracellular signaling for insulin action: the single gateway
      hypothesis.
AB  - Insulin resistance is a precursor to and primary cause of Type 2 diabetes
      mellitus. In addition, insulin resistance is associated with other chronic
      diseases, including gestational diabetes, cardiovascular disease, and cancer.
      Resistance to insulin's effects on carbohydrate metabolism include diminished
      actions of insulin to enhance glucose uptake and suppress endogenous glucose
      production. This chapter introduces new concepts related to the mechanism by
      which insulin stimulates glucose utilization in vivo and demonstrates that these
      processes are mechanistically linked to glucose production. Insulin acts rapidly
      in vitro to stimulate glucose uptake; in contrast, its effects in vivo are
      relatively slow in the conscious animal or human subject. The explanation for
      this difference between in vitro and in vivo dynamics is the delay associated
      with insulin transport across capillary endothelium of insulin-sensitive tissues
      (primarily muscle). Also, interstitial insulin is attenuated in concentration
      compared to plasma insulin at basal as well as under hyperinsulinemic conditions
      (plasma:interstitial ratio, 3:2). The sluggishness of insulin action and the
      attenuation in insulin concentration can be explained by a model in which
      transendothelial insulin transport is restricted and interstitial insulin binds
      to insulin-sensitive cells, where the hormone is internalized and degraded.
      Whether insulin transport occurs by a hormone-specific mechanism (i.e., via
      receptors on endothelial cells) was tested by comparing transport at
      physiological with pharmacological insulin concentrations-evidence supports a
      nonspecific mechanism of transport across endothelium (i.e., diffusion or
      transcytosis). Transendothelial transport alters the in vivo patterns of insulin
      signaling-biphasic plasma insulin after glucose injection is reflected in a
      simple, rapid increase in interstitial insulin to an elevated concentration. The
      time course of insulin's effect to suppress endogenous glucose output is a mirror
      image of its effect to enhance glucose uptake; however, there is no
      transendothelial barrier to insulin action at the liver. The similarity in action
      dynamics at periphery and liver was explained by a mechanism in which insulin
      crosses into peripheral tissue and alters a "second (blood-borne) signal" that,
      in turn, suppresses liver glucose production. Of various possible alternative
      candidates for the second signal, declining plasma free fatty acids appear to
      signal suppression of glucose production. We have proposed the "single gateway
      hypothesis" to explain insulin's action on carbohydrate metabolism in vivo:
      insulin crosses the endothelial boundary in skeletal muscle (to stimulate glucose
      disposal) and traverses the endothelial barrier in adipose tissue to suppress
      lipolysis. The declining free fatty acids are proposed to be a major factor in
      the insulin-mediated decline in glucose output. This mechanism can be contrasted
      with the classical concept that portal insulin controls the liver directly.
      Recent evidence supports the concept that, under normal levels of glucagonemia,
      less than 25% of the suppression of hepatic glucose output by insulin is due to a
      direct effect of insulin via the portal vein and that most of the effect
      (approximately 75%) is explained by the indirect single gateway mechanism. These
      results raise the question of whether hepatic insulin resistance in Type 2
      diabetes can be explained by insulin resistance at the adipocyte, which causes a
      failure of reduction of FFA by insulin, leading to overproduction of glucose by
      the liver. The possible role of the single gateway mechanism in diabetes is under
      investigation.

PMID- 9238860
TI  - Regulation and properties of the rat Ca2+/calmodulin-dependent protein kinase IV
      gene and its protein products.
AB  - Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a monomeric
      multifunctional enzyme that is expressed only in subanatomical portions of the
      brain, T lymphocytes, and postmeiotic male germ cells. It is present in the
      nucleus of the cells in which it is expressed and can phosphorylate and activate
      the cyclic AMP response element binding proteins CREB and CREM tau in a manner
      analogous to protein kinase A. In the absence of Ca2+/calmodulin, CaMKIV is
      inactive. Activation requires three events: 1) binding of Ca2+/calmodulin; 2)
      phosphorylation of a single threonine residue present in the activation loop by a
      separate protein kinase that is also Ca2+/calmodulin-dependent; and 3)
      autophosphorylation of serine residues present in the extreme N-terminus that is
      required to relieve a novel form of autoinhibition. The gene for rat CaMKIV has
      been cloned and found to span 42 kb of DNA. The gene encodes three proteins:
      namely, the alpha and beta forms of CaMKIV that differ only in that the beta form
      contains a 28 amino acid N-terminal extension as well as calspermin. Calspermin
      is the C-terminal 169 amino acids of CaMKIV that binds Ca2+/calmodulin and is
      expressed only in postmeiotic male germ cells. The promoter for calspermin
      resides in the penultimate intron of the CaMKIV gene and is regulated by two
      CREs. This promoter is sufficient to faithfully target expression of a reporter
      gene to the postmeiotic male germ cells of transgenic mice. Transgene expression
      can be induced in cells from the transgenic mice that do not normally express it
      by transfection of CREM tau and CaMKIV. These data suggest that rearrangement of
      chromatin during meiosis together with the expression of CREM tau at high levels
      are sufficient to control expression of the calspermin promoter during
      spermatogenesis. On the other hand, the developmental expression of CaMKIV in
      brain and thymus appears to be controlled by thyroid hormone mediated via the
      thyroid hormone receptor alpha. In T lymphocytes, CaMKIV will phosphorylate CREB
      in response to signals that result in T cell activation. Transgenic mice that
      express a kinase minus mutant of CaMKIV specifically in thymic T cells show a
      marked reduction of total thymic cellularity. The remaining T cells undergo a
      much greater than normal rate of spontaneous apoptosis when placed in culture.
      These cells fail to generate the signals to phosphorylate CREB and produce
      significantly less of the cytokine Interleukin-2 (IL-2) in response to agents
      that either increase intracellular Ca2+ and/or activate protein kinase C.
      Collectively, the data suggest that CaMKIV may be involved both in preventing
      apoptosis during T cell development and also in the early cascade of events that
      is required to activate the mature T cells in response to a mitogenic stimulus.

PMID- 9238861
TI  - Anchoring and scaffold proteins for kinases and phosphatases.
AB  - Many hormones mediate their intracellular actions by triggering signal
      transduction pathways that alter the phosphorylation state of key regulatory
      proteins. Protein phosphorylation is a reversible process involving two classes
      of signaling enzymes: protein kinases, which catalyze the transfer of phosphate
      from ATP onto substrate proteins, and phosphoprotein phosphatases, which perform
      the dephosphorylation step. To insure tight control of hormonally initiated
      phosphorylation events, the activity of multifunctional kinases and phosphatases
      is precisely regulated and responds to fluctuations in diffusible second
      messengers such as Ca2+, phospholipid, and cAMP. Another mechanism that
      contributes to their regulation is to restrict the location of these enzymes to
      certain subcellular compartments. Subcellular targeting enhances the selectivity
      of serine/threonine phosphatases and kinases by favoring their accessibility to
      certain substrate proteins. Compartmentalization is achieved through a "targeting
      moiety," which is defined as that part of a phosphatase or kinase that directs
      the catalytic subunit to a certain subcellular environment. The targeting moiety
      restricts the location of a phosphatase or kinase through association with a
      "targeting locus." These are often structural membrane proteins, cytoskeletal
      components, or cellular organelles. Targeting subunits for the type I phosphatase
      and protein kinase C have been identified; however, the focus of this chapter
      centers around a family of anchoring proteins, called AKAPs, that localize the
      type II cAMP-dependent protein kinase (PKA). Structure-function analysis suggest
      that each anchoring protein binds to the RII dimer through a conserved
      amphipathic helix region and is tethered to specific subcellular sites via
      association of a targeting domain with structural proteins or cellular
      organelles. Peptides patterned after the amphipathic region have been used to
      probe the functional significance of PKA anchoring inside cells and have begun to
      be established by that disruption RII/AKAP interaction in vivo has concomitant
      effects on certain PKA-mediated phosphorylation events. In addition, multivalent
      binding proteins such as AKAP79 and AKAP250 have been characterized and appear to
      serve as platforms for the assembly of kinase/phosphatase signaling complexes.
      Collectively, these studies suggest that the AKAPs represent a growing family of
      regulatory proteins that provide a molecular architecture that organizes the
      intracellular location of a single or multiple multifunctional kinase.

PMID- 9238862
TI  - Interaction, signal generation, signal divergence, and signal transduction of
      LH/CG and the receptor.
AB  - The LH/CG receptor is comprised of two structurally and functionally distinct
      domains, extracellular N-terminal exodomain and membrane-embedded endodomain.
      These two domains can separately be expressed and processed, including folding.
      The exodomain alone has the high-affinity hormone binding site but is not capable
      of generating hormonal signal. In contrast, the endodomain alone has the site for
      receptor activation. These two domains contact each other in holo-receptor and
      split receptor. This interaction, particularly through exoloops 2 and 3,
      constrains the high-affinity hormone binding at the exodomain. Conversely, the
      exodomain could be involved in receptor activation. Therefore, these two domains
      are not entirely independent, although they can be independently synthesized and
      processed. The existing evidence indicates that hCG and the receptor undergo
      multiple stages of interactions leading to receptor activation. Initial high
      affinity binding of hCG to the exodomain results in conformational adjustments of
      the hCG/exodomain complex. This leads to the secondary, low-affinity contact of
      the hCG/exodomain complex with the endodomain. This secondary contact is
      responsible for generating signals. They are transduced through transmembrane
      domains (TM) to the cytoplasmic portion (cytoloops and the C-terminal tail) of
      the receptor and then transferred to cytoplasmic signaling molecules such as G
      protein. Mutations in the exodomain and endodomain (N-extension, exoloops, TM,
      cytoloops, and cytoplasmic tail) have the potential to interfere with receptor
      activation at different steps: signal generation, transduction, and transfer.
      Binding of hCG to the LH/CG receptor is known to induce two signals, one for
      adenylyl cyclase/ cAMP and the other for phospholipase C/inositol
      phosphate/diacylglycerol. The cAMP signal and IP signal diverge at the surface of
      the receptor. These independent signals are separately transduced through the
      transmembrane domains to the cytoplasmic part of the receptor, indicating the
      existence of the distinct transducers for each of the signals. Furthermore, it is
      likely that the divergent signals are separately transferred to cytoplasmic
      signal molecules such as G protein. In addition, each cAMP signal and IP signal
      consists of at least three separate subsignals: affinity signal, maximal
      production (efficacy) signal, and basal level signal. In heterodimeric hCG there
      are distinct parts responsible for high-affinity receptor binding and receptor
      activation. Particularly, the C-terminal residues of the alpha subunit play a
      crucial role in receptor activation. This alpha subunit is shared with other
      glycoprotein hormones, follicle-stimulating hormone, and thyroid-stimulating
      hormone. Interestingly, the alpha C-terminal residues play distinct roles in all
      three hormones, despite its common nature.

PMID- 9238863
TI  - Changing through doing: behavioral influences on the brain.
AB  - It seems self-evident that the brain controls behavior but does behavior also
      "control" the brain? This chapter examines evidence that behavior can and does
      influence specific aspects of brain structure and function. Evidence for such
      influence is easily obtained on an evolutionary time scale, since the selective
      forces found in the ecological niche of the animal are typically reflected in its
      sensory and motor activities as well as its body shape and behavioral habits.
      Similarly, during development, there is ample evidence that the behavior acts in
      concert with the environment to establish structural changes in the brain that
      last a lifetime. Perhaps most surprisingly there is now evidence that social
      behavior can cause changes in the brain in adult animals and that these changes
      are reversible. The changes caused by behavioral interactions can be dramatic and
      typically are related to reproductive behavior. Understanding the mechanisms
      responsible for dynamic changes in the nervous systems of adult animals is a
      major challenge and the discovery that it can occur may lead to insights about
      other systems where behavior sculpts the brain.

PMID- 9238865
TI  - Secondary structure of the 5'-noncoding region of border disease virus genome
      RNAs.
AB  - The computer predicted secondary structures from the 5'-NC genome region of four
      border disease virus (BDV) strains collected from sheep in England and Scotland
      over a period 1976-1986 were prepared. The FOLD program from GCG sequence
      analysis software package was used for the analysis of a 243 bp RNA fragment. Two
      typical shapes of secondary structures were observed which contained multiple
      imperfect stem-loop motifs. The shape of those structures exactly fit with the
      grouping of BDV strains to two phylogenetic groups. Secondary structures are
      typical only of BDV strains and they are different from the structures prepared
      for NADL (BVDV) and Alfort (CSFV) strains.

PMID- 9238864
TI  - Brain gonadotropin releasing hormone receptors: localization and regulation.
AB  - In this review, the current information about the location of GnRH receptor
      protein and GnRH receptor mRNA in the rat central nervous system is summarized as
      well as the changes that occur in the GnRH receptor mRNA levels during different
      endocrine conditions of the animals. The results of these studies show that GnRH
      receptor protein and mRNA levels change in parallel in the hippocampus,
      suggesting that pretranscriptional factors control the synthesis of the receptor.
      In the arcuate and ventromedial nuclei of the hypothalamus, GnRH receptor mRNA
      levels are highest during the early morning of proestrus and during the morning
      of an estrogen-progesterone-induced LH surge. The timing of the changes in GnRH
      receptor mRNA levels indicates that increasing levels of estradiol are
      responsible for the increase in GnRH receptor synthesis. Binding of GnRH agonist
      to the brain GnRH receptor causes a dose-dependent increase in inositol
      phosphates as well as changes in intracellular Ca++ levels of the target neurons.
      Together, it is suggested that GnRH functions in the brain as a neurotransmitter
      and/or modulator linking the peripheral endocrine effects of GnRH to actions of
      the peptide inside the central nervous system where it can facilitate, for
      example, reproductive behaviors.

PMID- 9238866
TI  - A review of plaque, gingivitis, calculus and caries clinical efficacy studies
      with a fluoride dentifrice containing triclosan and PVM/MA copolymer.

PMID- 9238867
TI  - An overview of established interdental cleaning methods.
AB  - The removal of interproximal plaque is considered to be important for the
      maintenance of gingival health, prevention of periodontal disease and the
      reduction of caries. Unfortunately, the toothbrush is relatively ineffective at
      removing interproximal plaque, and therefore patients need to resort to
      additional techniques. Floss, woodsticks, rubber tips and interdental brushes
      currently represent the primary methods available for interproximal cleaning. No
      one method suits all patients and it is difficult for any of these methods to
      access the posterior dentition. Floss is the most widely used method of
      interdental cleaning and the American Dental Association reports that up to 80%
      of interdental plaque may be removed by this method, resulting in a significantly
      reduced incidence of caries and prevention of periodontal disease. The main
      problem with all interdental cleaning is, however, patient ability and
      motivation. Patients are known to find flossing difficult, especially where there
      are tight contact points, and therefore interdental cleaning does not readily
      become an established part of daily oral hygiene. As such, there is a need for
      new techniques/devices to be developed that will make interdental cleaning easier
      and improve patient motivation. Results of clinical and laboratory studies have
      indicated that the Braun Oral-B Interclean (ID2) is a safe and effective device
      for the reduction of interproximal plaque and the control of gingivitis. In
      addition, the ID2 was preferred by the majority of volunteers to conventional
      floss.

PMID- 9238868
TI  - A clinical study of the safety and efficacy of a novel electric interdental
      cleaning device.
AB  - The safety and efficacy of an electric interdental cleaning device, the Braun
      Oral-B Interclean (ID2) (Braun AG, Kronberg, Germany), and an American Dental
      Association-approved manual floss were compared over a four-week period for their
      effect on interproximal plaque, gingivitis and papillary bleeding with 52 healthy
      volunteers. Eligible subjects had a complete dental examination before being
      randomly assigned to one of the two experimental groups. Subjects underwent a
      dental prophylaxis before receiving instructions in the use of their assigned
      device. The three parameters of plaque, gingivitis and papillary bleeding were
      evaluated at Days 1 and 30. The results showed a significant reduction from
      baseline in all three parameters for both treatment groups (p < 0.001) over the
      four-week period. There was a trend toward somewhat less interproximal plaque
      regrowth for subjects using manual floss over four weeks compared with those
      using the ID2, but the difference between groups was not statistically
      significant. The reduction in gingivitis was comparable between the groups.
      Similar reductions in papillary bleeding were demonstrated in the two groups. No
      significant soft tissue pathology was noted in either group. The results
      demonstrated no statistically significant difference between manual floss and the
      novel electric interdental cleaning device (ID2). After the 30-day clinical
      assessment, subjects entered the personal preference phase of the study. Each
      group crossed over to the other interdental cleaner, was instructed in its use,
      and directed to use it for an additional 30 days. At the end of this time, all
      subjects completed a questionnaire. Results from this part of the study revealed
      that significantly more subjects preferred the ID2 (69.5%) to floss (24.5%). Only
      6% expressed no preference.

PMID- 9238869
TI  - An investigation of the efficacy and safety of a new electric interdental plaque
      remover for the reduction of interproximal plaque and gingivitis.
AB  - This clinical study was conducted to compare the efficacy and safety of the new
      Braun Oral-B Interclean (ID2) with that of dental floss in healthy adults.
      Volunteers with sufficient dental plaque and gingivitis were randomized to use
      the ID2 (n = 24) or American Dental Association-approved dental floss (n = 24) in
      conjunction with toothbrushing once nightly for 6 weeks. All subjects received a
      supragingival prophylaxis and polishing at the start of the study. Over the study
      period, both devices produced significant reductions in interproximal plaque,
      gingivitis and bleeding (p < 0.01). With the ID2, there were reductions in
      interproximal plaque scores (all sites) of approximately 40% compared with 28%
      with dental floss. A decrease in gingivitis of 15% was observed with the ID2
      compared with 12% for floss users. Bleeding on probing was reduced by 25% with
      the ID2 and by 34% with dental floss. There was a trend in favor of the ID2 with
      respect to reduction in plaque which achieved statistical significance (p = 0.05)
      for the posterior three interproximal sites. Differences between treatment groups
      with respect to gingivitis and bleeding reductions were not statistically
      significant. No adverse events were reported or observed during the study. It is
      concluded that the ID2 has equivalent efficacy to dental floss for the reduction
      of interproximal plaque and gingivitis.

PMID- 9238870
TI  - Hard tissue abrasivity of an automatic interdental plaque remover.
AB  - This laboratory study was conducted to assess the safety of a new interdental
      cleaner, the Braun Oral-B Interclean (ID2), by measuring its abrasivity to dentin
      and comparing this with the abrasivity of a standard ADA manual toothbrush when
      used with and without dentifrice. Dentin abrasion was measured by a radioactive
      technique, using a modified ADA-recommended methodology. Dentin specimens to be
      used with the ID2 had a 2 mm hole drilled through them to represent the
      interproximal space, whereas dentin slabs were used in the toothbrush abrasivity
      tests. All specimens were placed in a controlled neutron flux. The dentin
      specimens were then immersed either in an abrasive dentifrice (Crest) slurry or a
      non-abrasive (water) solution, and an 8.5 minute treatment carried out. After
      testing, samples of treatment slurry or solution were put in a scintillation
      counter and mean net counts per minute (cpm) per gram of slurry or solution were
      calculated. With Crest dentifrice, the ID2 removed significantly less (p < or =
      0.05) dentin (232 cpm/g) than the ADA reference manual toothbrush (789 cpm/g).
      Without dentifrice, neither the ID2 nor the manual toothbrush removed significant
      amounts of dentin, and dentin loss was similar for both devices.

PMID- 9238871
TI  - Recent advances in clinical research on toothpastes and mouthwashes: clinical
      efficacy of commercial products for gingivitis, tartar control and antimicrobial
      activity.

PMID- 9238872
TI  - A comparison of stabilized stannous fluoride dentifrice and triclosan/copolymer
      dentifrice for efficacy in the reduction of gingivitis and gingival bleeding: six
      month clinical results.
AB  - This parallel-group, double-blind, placebo-controlled clinical trial directly
      compared the efficacy of two antimicrobial dentifrice formulations for the
      control of plaque, gingivitis and gingival bleeding during six months of use
      following a pre-test randomization period. Test antimicrobial dentifrices for the
      study included: a stabilized stannous fluoride formulation (Crest Plus Gum Care
      currently marketed in U.S.) comprised of 0.454% SnF2 in a stabilized silica
      abrasive base; and a formulation containing triclosan (Colgate Total, currently
      marketed outside the U.S. in numerous countries) comprised of 0.30% triclosan.
      2.0% Gantrez co-polymer and 0.243% NaF in a silica abrasive base. The control
      dentifrice was a conventional fluoride dentifrice comprised of 0.243% NaF in a
      silica abrasive base. Clinical evaluations included Turesky et al. plaque, Loe
      Silness gingivitis and gingival bleeding, and Meckel stain. The stabilized
      stannous fluoride dentifrice exhibited significant efficacy in the reduction of
      both gingivitis (20.5%) and gingival bleeding (33.4%) after six months relative
      to the placebo control (p < 0.05). In direct comparison, the stabilized stannous
      fluoride dentifrice reduced gingivitis and gingival bleeding significantly
      relative to the triclosan/copolymer dentifrice (p < 0.05). These results
      establish: 1) the superior clinical efficacy of a stabilized stannous fluoride
      dentifrice relative to a triclosan/copolymer dentifrice in the chemotherapeutic
      control of gingivitis and gingival bleeding; 2) the important contribution of
      clinical test design/sensitivity in assessing the therapeutic efficacy of
      antimicrobial agents; and 3) the value of head-to-head comparative studies in
      establishing the therapeutic relevance of clinical effects of formulations for
      the reduction of gingivitis.

PMID- 9238873
TI  - The comparative efficacy of stabilized stannous fluoride dentifrice,
      peroxide/baking soda dentifrice and essential oil mouthrinse for the prevention
      of gingivitis.
AB  - This double-blind parallel-design clinical study compared the efficacy of a
      stabilized stannous fluoride dentifrice (Crest Plus Gum Care), baking soda and
      peroxide (NaF) dentifrice (Mentadent), and essential oil mouthrinse (Listerine)
      to a conventional NaF dentifrice (Crest) for the control of plaque, gingivitis
      and gingival bleeding over six months. Following an initial baseline examination
      and stratification, subjects received a complete oral prophylaxis and were
      distributed assigned test products. Following three and six months, subjects re
      visited the clinic for examinations. Evaluations at baseline and at 3 and 6
      months included soft tissue status. Loe-Silness gingivitis/gingival bleeding,
      Silness-Loe plaque and dental stain. Results subsequent to six months of product
      use were as follows: At six months, the stabilized stannous fluoride dentifrice
      was observed to produce statistically significant 17.5% reductions in gingivitis
      and 27.5% reductions in gingival bleeding relative to the NaF dentifrice. The
      combination of sodium fluoride dentifrice and essential oil mouthrinse produced
      statistically significant reductions of 7.4% in gingivitis and 10.8% in plaque as
      compared with the NaF dentifrice. The stabilized stannous fluoride dentifrice
      produced statistically significant reductions in both gingivitis (10.8%) and
      gingival bleeding (23.0%) relative to the combination of sodium fluoride
      dentifrice and essential oil mouthrinse. The baking soda and peroxide (NaF)
      dentifrice did not provide reductions in gingivitis, plaque or gingival bleeding
      as compared with the conventional NaF dentifrice. The stabilized stannous
      fluoride dentifrice provided statistically significant reductions in gingivitis
      as compared with the baking soda and peroxide dentifrice following six months of
      use, and both the essential oil mouthrinse and stabilized stannous fluoride
      dentifrice provided statistically significant reductions in gingivitis as
      compared with the baking soda and peroxide dentifrice following three months of
      use. These results support: 1) the efficacy of stabilized stannous fluoride
      dentifrice and the combination of sodium fluoride dentifrice and essential oil
      mouthrinse for the prevention of gingivitis; 2) the superior activity of
      stabilized stannous fluoride dentifrice as compared with a combination of sodium
      fluoride dentifrice and essential oil mouthrinse for the control of gingivitis
      and gingival bleeding; and 3) the lack of efficacy for baking soda and peroxide
      dentifrice for the control of plaque, gingivitis and gingival bleeding as
      compared with conventional fluoridated dentifrice.

PMID- 9238874
TI  - A comparison of intraoral antimicrobial effects of stabilized stannous fluoride
      dentifrice, baking soda/peroxide dentifrice, conventional NaF dentifrice and
      essential oil mouthrinse.
AB  - The intraoral antimicrobial activity of four commercial oral products
      conventional NaF dentifrice (Crest), baking soda/peroxide/NaF dentifrice
      (Mentadent), essential oil mouthrinse (Listerine) and SnF2 dentifrice (Crest Plus
      Gum Care)-have been compared in three test regimens. Formulations were compared
      for their ability to suppress the regrowth and apical extension of dental plaque
      following toothbrushing during thirty hours of non-brushing where products were
      used as oral rinses (30-hour plaque regrowth model). Formulations were also
      compared for their ability to suppress the colony-forming units (cfu) of
      facultative anaerobic bacteria sampled from buccal gingival surfaces following
      use (Gingival Surface Microbial Index-GSMI model). Lastly, formulations were
      compared for effects in suppressing the glycolytic metabolic activity and
      regrowth activity of in vivo-treated dental plaques sampled at various periods
      following topical use and incubated under controlled ex vivo conditions (Plaque
      Glycolysis and Regrowth-PGRM model). In thirty-hour plaque regrowth testing, the
      rank ordered antimicrobial efficacy of formulations followed SnF2 > essential
      oils > NaF = water = baking soda/peroxide. In GSMI testing, all formulations were
      shown to suppress the cfu of facultative anaerobic bacteria relative to baseline,
      although SnF2 treatment was observed to reduce bacterial levels to a
      significantly greater degree than NaF dentifrice or baking soda/peroxide
      dentifrice up to two hours following brushing. In PGRM testing, the SnF2
      dentifrice provided significant inhibition of bacterial metabolism and regrowth
      following topical application when compared with the NaF dentifrice as control.
      The baking soda/peroxide dentifrice provided no reduction in either bacterial
      metabolism or regrowth in PGRM. Previous studies had demonstrated modest effects
      for essential oil rinse in reducing PGRM plaque regrowth, with no effects for
      this treatment on plaque metabolism. Overall, these results demonstrate that SnF2
      dentifrice provides substantial intraoral antimicrobial effects. The essential
      oil mouthrinse also exhibits significant intraoral antimicrobial effects, albeit
      apparently less than SnF2 dentifrice. The baking soda/peroxide dentifrice did not
      produce any antimicrobial effects following in vivo use compared with
      conventional dentifrice. These results provide mechanistic rationale for the
      chemotherapeutic efficacy of SnF2 and essential oil formulations in reducing
      gingivitis, while providing no support for the expectation of clinical efficacy
      for formulations containing baking soda and peroxide.

PMID- 9238876
TI  - Clinical relevance of adaptation to sorbitol by plaque bacteria: a review.

PMID- 9238875
TI  - The comparative clinical efficacy of pyrophosphate/triclosan, copolymer/triclosan
      and zinc citrate/triclosan dentifrices for the reduction of supragingival
      calculus formation.
AB  - Three triclosan-containing "multi-benefit" dentifrices were compared for clinical
      efficacy in reducing supragingival calculus formation following a dental
      prophylaxis. A total of 544 subjects completed a double-blind parallel-group
      clinical study using the Volpe-Manhold Index (VMI) to record severity and
      occurrence of supragingival calculus. The study design included a pre-test period
      where the calculus formation rate was measured in subjects brushing with a
      placebo dentifrice. Following a prophylaxis, subjects were stratified for age,
      gender and VMI scores and assigned to one of four treatments: 1) a dentifrice
      containing 5.0% soluble pyrophosphate/0.145% fluoride as NaF/silica
      abrasive/0.28% triclosan (hereafter PPi/TCS-comparable to Crest Complete
      dentifrice, Procter & Gamble, UK); 2) a commercial dentifrice containing 2.0%
      Gantrez acid copolymer/ 0.145% fluoride as NaF/silica abrasive/0.30% triclosan
      (hereafter Gan/TCS-Colgate Total dentifrice, Colgate-Palmolive Company, UK); 3) a
      commercial dentifrice containing 0.5% zinc citrate trihydrate/0.15% fluoride as
      sodium monofluorophosphate/silica abrasive/0.20% triclosan (hereafter Zn/TCS
      Mentadent P dentifrice, Unilever, UK); and 4) a control dentifrice comprised of
      0.145% fluoride as NaF/silica abrasive (hereafter Control). Subjects were
      instructed to use their assigned dentifrice at least twice per day and to brush
      as they do normally. Supragingival calculus formation was assesed at two and four
      months using site-specific and whole-mouth VMI indices for both calculus severity
      and occurrence. Following four months of use, the PPi/TCS dentifrice provided
      statistically significant reductions in calculus severity (22-23%) and occurrence
      (15%) as compared with the Control dentifrice. The Zn/TCS dentifrice also
      provided significant reductions in calculus severity (17-19%) and occurrence (12
      13%) as compared with the Control. The Gan/TCS produced no statistically
      significant reductions in calculus formation (occurrence or severity) compared
      with the Control. The PPi/TCS dentifrice provided statistically significant
      reductions in calculus severity (15-21%) and occurrence (12-16%) as compared with
      the Gan/TCS dentifrice. These results support the clinical effectiveness of
      PPi/TCS and Zn/TCS dentifrices for the reduction of supragingival dental calculus
      formation following a dental prophylaxis.

PMID- 9238877
TI  - Salivary fluoride content after toothbrushing with a sodium fluoride and an amine
      fluoride dentifrice followed by different mouthrinsing procedures.
AB  - The aim of the present study was to determine the salivary fluoride content after
      toothbrushing with a sodium fluoride and amine fluoride dentifrice followed by
      two different mouthrinsing procedures. Twenty-four dental students took part in
      this six-treatment, six-period study with a cross-over design. They brushed their
      teeth with an amine fluoride, a sodium fluoride, and a non-fluoridated
      dentifrice. After toothbrushing the subjects spat out the saliva/dentifrice
      slurry and underwent one of the following procedures: 1) mouthrinsing with 20 ml
      distilled water; 2) no mouthrinsing after spitting out. Whole saliva samples were
      collected before (baseline), 10 and 90 min after toothbrushing and mouthrinsing,
      respectively. Fluoride analysis was performed with a fluoride-sensitive
      electrode. Both dentifrices caused an elevated fluoride level in saliva after
      brushing. Use of the amine fluoride dentifrice resulted in higher salivary
      fluoride contents compared to the sodium fluoride toothpaste. However, this
      difference was statistically significant only 90 min after toothbrushing when
      preceded by mouthrinsing after brushing. Mouthrinsing with water after brushing
      led to significantly lower fluoride levels compared to the non-rinsing technique
      10 min after brushing. Mouthrinsing after toothbrushing with fluoride dentifrices
      reduces the salivary fluoride concentration of both an amine and a sodium
      fluoride dentifrice.

PMID- 9238878
TI  - Clinical evaluation of a dental rinse containing aluminum lactate for treatment
      of dentinal hypersensitivity.
AB  - The effectiveness of a dental rinse containing aluminum lactate, which was used
      as a daily home treatment for dentinal hypersensitivity, was evaluated in a 6
      week, double-blind study. Fifty-six subjects who complained of cold and/or
      tactile hypersensitivity were randomly divided into two groups: one given a
      dental rinse containing 2.18% aluminum lactate (test group) and the other a
      vehicle control dental rinse (control group). Subjects in both groups were
      instructed to rinse with the assigned dental rinse and to brush their teeth twice
      daily. The hypersensitivity levels of the affected teeth were assessed at
      baseline and at 4 and 6 weeks by application of tactile, cold air and cold water
      stimuli, and scored against baseline. All hypersensitivity scores in both groups
      were decreased significantly at weeks 4 and 6 compared to the baseline (p <
      0.001). The hypersensitivity scores for tactile, cold air and cold water stimuli
      in the test group were significantly lower at weeks 4 and/or 6 compared to those
      in the control group (p < 0.05). Furthermore, on the analysis for the teeth with
      apparent pain (score 2 or 3) at the baseline, the reduction rates of
      hypersensitivity scores for cold air and cold water stimuli in the test group
      were significantly greater than those in the control group (p < 0.05). These
      findings suggest that daily home use of a dental rinse containing aluminum
      lactate is effective for treatment of dentinal hypersensitivity.

PMID- 9238879
TI  - Marginal leakage of combinations of glass-ionomer and composite resin
      restorations.
AB  - This study compared the microleakage of four different combinations of glass
      ionomer and composite resin restorations. Forty class V cavities were prepared in
      permanent posterior teeth. The gingival margin of the cavities were placed in
      cementum and the occlusal wall in enamel. The cavities were restored as either 1)
      light-cured glass-ionomer cement (LC-GIC); 2) chemically cured glass-ionomer
      cement (CC-GIC); 3) composite resin (with dentin bonding agent); or 4) light
      cured glass-ionomer and composite resin (sandwich). Marginal microleakage was
      assessed by methylene blue dye penetration after thermocycling between 5 degrees
      C and 60 degrees C for 300 cycles. Microleakage of LC-GIC restorations and the
      dentin-bonded composite resin restorations were significantly lower than the CC
      GIC and the LC-GIC sandwich technique restorations. There was no significant
      difference in the microleakage between the LC-GIC and the dentin-bonded composite
      resin restorations. The degree of microleakage of the sandwich restorations was
      significantly lower than the CC-GIC restorations. Light-cured glass-ionomer and
      dentin bonded composite resin restorations exhibited a lower degree of leakage
      than the glass-ionomer/composite sandwich and chemically cured glass-ionomer
      restorations at the gingival margins of class V restorations.

PMID- 9238880
TI  - The clinical effect of a newly designed electric toothbrush on supragingival
      plaque, gingivitis and gingival bleeding.
AB  - A clinical study was carried out in an attempt to assess the efficacy of a newly
      designed electric toothbrush compared to a conventional manual toothbrush using
      the American Dental Association's protocol for evaluating toothbrushes. An Oral-B
      35 manual toothbrush, which served as the control, was compared to the Plaq &
      White125 electric toothbrush. Examinations were performed by two calibrated
      examiners at baseline, day 15 and day 30. Examinations included the gingival
      index, plaque index and bleeding index. Mean indices were calculated and compared
      between the two brushes using the repeated measures multiple analysis of
      variance. No statistically significant differences between the mean indices on
      the three examination days were observed following the use of the manual or the
      electric toothbrushes. The results of this study demonstrate that the electric
      toothbrush was numerically more effective than the manual toothbrush in reducing
      supragingival plaque levels, either before or after brushing, at each examination
      date compared to baseline plaque values. However, this difference was not
      statistically significant. This and other findings concluded that the Plaq &
      White toothbrush is comparable to the control ADA-accepted toothbrush.

PMID- 9238881
TI  - A comparative evaluation of the in vitro penetration performance of the improved
      Crest complete toothbrush versus the Current Crest complete toothbrush, the
      Colgate Precision toothbrush and the Oral-B P40 toothbrush.
AB  - Removal of plaque and debris from interproximal surfaces during toothbrushing has
      generally been difficult to achieve, in large part because traditional flat
      bristled toothbrushes do not offer good interproximal penetration. As a result, a
      number of varying bristle designs have been developed, with the rippled-design
      brush shown to be particularly effective at removing interproximal plaque.
      Recently, an existing brush, the original Crest Complete, was modified to offer a
      more deeply rippled version. This study evaluated the interproximal penetration
      of four bristle designs: rippled pattern (original Crest Complete), deeper
      rippled pattern (improved Crest Complete), multi-level (Colgate Precision), and
      flat-tufted (Oral-B P40). The study used a previously reported in vitro model for
      determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27
      33, 1994). In order to effectively mimic the in-use characteristics of
      toothbrushing, this model is based on analysis of videotaped consumer brushing
      habits, tooth morphology, and in vivo plaque tenacity characteristics and uses
      the three most predominantly used brushing techniques (circular, up-and-down, and
      back-and-forth, with the brush held at both 45 and 90 degrees to the tooth
      surface). In addition, the model's brush stroke length, brush force, and brush
      speed are likewise based on analysis of consumer brushing patterns. The results
      of the study indicate that the new Crest Complete with deeper rippled bristles
      provided significantly superior (p < or = 0.05) interproximal penetration than
      the Colgate Precision and Oral-B brushes overall and for three of the four brush
      strokes tested. In addition, the new Crest Complete was found to provide
      significantly superior interproximal penetration to the original Crest Complete
      overall and in circular and up-and-down strokes, and the original Crest Complete
      provided superior overall interproximal penetration to the Colgate and Oral-B
      brushes.

PMID- 9238882
TI  - Influence of dentin conditioning on bond strength of light-cured ionomer
      restorative materials and polyacid-modified composite resins.
AB  - The purpose of the study was to evaluate the dentin bond strength of restorative
      materials containing both glass ionomer and composite resin components. Three
      resin-modified glass ionomer restorative materials (Fuji II LC, Photac-Fil,
      Vitremer), three polyacid-modified composite resins (Dyract, Ionosit Fil,
      VariGlass VLC), a hybrid composite (blend-a-lux) and a chemical-cured glass
      ionomer cement (ChemFil Superior) were investigated for dentin tensile bond
      strength with and without conditioning of the tooth surfaces. For each material,
      tensile bond strength was determined using five conditioned and five
      unconditioned bovine tooth specimens. Conditioning of the specimens was performed
      according to the manufacturers' instructions. The tensile bond strength was
      tested with a universal testing machine. Statistical analysis was performed with
      analysis of variance, the Scheffe's-test and the Student's t-test. All materials
      showed higher adhesion to conditioned dentin than to unconditioned specimens.
      Except for Photac-Fil, the bond strength to conditioned dentin of all resin
      modified glass ionomer restorative materials and polyacid-modified composite
      resins was higher as compared to the chemical-cured glass ionomer and the hybrid
      composite. However, these differences were not statistically significant. All
      polyacid-modified composite resins resulted in higher bond strengths to
      conditioned dentin as compared to the resin-modified glass ionomer restorative
      materials. These differences were statistically significant only for VariGlass
      VLC as compared to Photac-Fil. In order to improve adhesion of the tested
      materials to dentin it is highly recommended to follow the manufacturers'
      instructions concerning dentin conditioning.

PMID- 9238883
TI  - Comparison of the clinical anticaries efficacy of an 1100 NaF silica-based
      dentifrice containing triclosan and a copolymer to an 1100 NaF silica-based
      dentifrice without those additional agents: a study on adults in California.
AB  - Recent years have seen much work in the development of dentifrices containing the
      antimicrobial agent triclosan, a broad spectrum antibacterial agent manufactured
      for use in oral products by the Ciba-Geigy Corporation. Studies have shown that
      the incorporation of this agent into dental products, in combination with a
      PVM/MA copolymer (the non-proprietary designation for a polyvinylmethyl
      ether/maleic acid copolymer), can provide several important dental therapeutic
      benefits, including an antigingivitis effect. Much research on the therapeutic
      benefits of such dentifrices has been reported in the literature. The present
      study is a component of a large-scale program of clinical research to investigate
      the anticaries effectiveness of fluoride dentifrices containing 0.3% triclosan
      and 2.0% PVM/MA copolymer. The study included two treatment groups, each
      consisting of adults living within a 50 mile radius of Loma Linda, California,
      who were assigned to the use of one of the following sodium fluoride (NaF)
      dentifrices: 1) a dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer
      in a 0.243% NaF/silica (1100 ppm F) base; or 2) a dentifrice containing 0.243%
      NaF/silica (1100 ppm F). Conducted in accordance with the guidelines for caries
      clinical studies published by the Council on Dental Therapeutics of the American
      Dental Association, the study employed clinical diagnostic criteria as described
      in the August, 1987 National Institute of Dental Research (NIH/NIDR) publication.
      Dental radiographs were not employed. Principal comparisons of the dentifrices
      tested were implemented through the construction of 90% confidence intervals for
      the ratio of mean 3-year caries increments, using Fieller's theorem. Of those
      subjects who met the initial inclusion/exclusion criteria for this study, 1,542
      were available for the 36-month examination. DFS (resp., DFT) increments over
      this period were 2.07 (0.63) for the triclosan/copolymer dentifrice, and 2.16
      (0.68) for the dentifrice without those additives. The confidence interval
      calculations for both incremental DFS and DFT support the conclusion that a
      dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer in a 0.243%
      NaF/silica (1100 ppm F) base provides a level of anticaries efficacy which is "at
      least as good as" that provided by a dentifrice containing 1100 NaF/silica
      without those additive agents. As such, the results of this clinical study
      clearly indicate that the addition of triclosan and a copolymer to a 1100
      NaF/silica dentifrice does not compromise its anticaries efficacy.

PMID- 9238884
TI  - Comparison of the clinical anticaries efficacy of a 1500 NaF silica-based
      dentifrice containing triclosan and a copolymer to a 1500 NaF silica-based
      dentifrice without those additional agents: a study on adults in Israel.
AB  - Recent years have seen much work in the development of dentifrices containing the
      antimicrobial agent triclosan, a broad spectrum antibacterial agent manufactured
      for use in oral products by the Ciba-Geigy Corporation. Studies have shown that
      the incorporation of this agent into dental products, in combination with a
      PVM/MA copolymer (the non-proprietary designation for a polyvinylmethyl
      ether/maleic acid copolymer), can provide several important dental therapeutic
      benefits, including an antigingivitis effect. A considerable amount of the
      research on the therapeutic benefits of such dentifrices has been reported in the
      literature. The present study is a component of a large-scale program of clinical
      research to investigate the anticaries effectiveness of fluoride dentifrices
      containing 0.3% triclosan and 2.0% PVM/MA copolymer. The study included two
      treatment groups, each consisting of adults living near the Kiryat Gat area in
      Israel, who were assigned to the use of one of the following sodium fluoride
      (NaF) dentifrices: 1) a dentifrice containing 0.3% triclosan and 2.0% PVM/MA
      copolymer in a 0.331% NaF/silica (1500 ppm F) base; or 2) a dentifrice containing
      0.331% NaF/silica (1500 ppm F). Conducted in accordance with the guidelines for
      caries clinical studies published by the Council on Dental Therapeutics of the
      American Dental Association, the study employed clinical diagnostic criteria as
      described in the August, 1987 National Institute of Dental Research (NIH/NIDR)
      publication. Dental radiographs were not employed. Principal comparisons of the
      dentifrices tested were implemented through the construction of 90% confidence
      intervals for the ratio of mean 3-year caries increments using Fieller's Theorem.
      Of those subjects who met the initial inclusion/exclusion criteria for this
      study, 1,296 were available for the 36-month examination. DFS (resp., DFT)
      increments over this period were 5.21 (1.30) for the triclosan/copolymer
      dentifrice, and 5.23 (1.39) for the dentifrice without those additives. The
      confidence interval calculations for both incremental DFS and DFT support the
      conclusion that a dentifrice containing 0.3% triclosan and 2.0% PVM/MA copolymer
      in a 0.331% NaF/silica (1500 ppm F) base provides a level of anticaries efficacy
      which is "at least as good as" that provided by a dentifrice containing 1500
      NaF/silica, without those additive agents. As such, the results of this clinical
      study clearly indicate that the addition of triclosan and a copolymer to a 1500
      NaF/silica dentifrice does not compromise its anticaries efficacy.

PMID- 9238885
TI  - A thirty-day evaluation of the Rowenta Dentiphant powered toothbrush in children
      for safety and efficacy.
AB  - A thirty-day clinical trial was undertaken with second grade school children to
      assess the safety and efficacy of a new battery-powered toothbrush (Rowenta
      Dentiphant) compared to the manual Oral-B 20 toothbrush. The children from four
      class rooms were individually and randomly assigned to use either product for the
      thirty days. The children reported to school having not brushed the morning of
      each assessment at baseline, 15 days and 30 days. Following the gingivitis
      assessment and given a pre-brushing plaque assessment, the children were
      instructed on the use of the toothbrush as they then brushed their teeth for a
      timed 1 minute out of sight of the examiners. The children were then reassessed
      for plaque removal. The results demonstrated that the children using the Rowenta
      powered toothbrush became used to the brush and improved their cleaning
      efficiency during the study. By week two, the buccal plaque scores for the
      Rowenta brush were significantly lower (p < 0.05) compared to the Oral-B 20
      group. By week four the Rowenta subjects had significantly lower buccal and
      lingual plaque scores after brushing, while the Oral-B 20 subjects had
      significantly lower buccal scores after toothbrushing, but no significant
      difference was found after brushing on lingual surfaces for plaque removal. On
      total plaque area scores, the Rowenta group was significantly lower (p < 0.01)
      than the Oral-B 20 group at both two and four weeks. The Rowenta group had a 10%
      reduction in plaque area after brushing comparing baseline to four weeks. The
      Oral-B group demonstrated no percentage difference in after brushing plaque
      scores from baseline to four weeks. On gingivitis, the Rowenta group had
      significantly lower buccal and lingual mean scores compared to the Oral-B 20
      group at week two, and lingual mean scores compared to the Oral-B 20 group at
      week four. The Rowenta group demonstrated a 27% decrease in lingual gingivitis
      scores compared to baseline, while the Oral-B group had an 11% decrease in
      lingual gingivitis scores from baseline to four weeks. Total gingivitis scores
      for the Rowenta group were significantly lower (p < 0.01-0.001) at both weeks two
      and four compared to the Oral-B 20 group, with percentage declines from baseline
      to four weeks being 22% and 12%, respectively. The Rowenta Dentiphant toothbrush
      was found to be safe to use. On total plaque and gingivitis reduction, the
      Rowenta Dentiphant toothbrush was found to be significantly superior to the Oral
      B 20 manual toothbrush by two weeks of use and this continued to the conclusion
      of the study.

PMID- 9238886
TI  - A comparative evaluation of the in vitro penetration performance of the improved
      Crest Complete toothbrush versus the Colgate Total toothbrush and the Oral-B
      Advantage toothbrush.
AB  - Removal of plaque and debris from interproximal surfaces during toothbrushing has
      generally been difficult to achieve, in large part because traditional flat
      bristled toothbrushes do not offer good interproximal penetration. As a result, a
      number of varying bristle designs have been developed, with the rippled-design
      brush shown to be particularly effective at removing interproximal plaque.
      Recently, an existing rippled brush, the original Crest Complete, was modified to
      offer longer rippled outer tufts to clean along the gumline more effectively.
      Therefore, this study evaluated the overall and gumline interproximal penetration
      of three bristle designs: rippled, raised pattern (Improved Crest Complete); and
      two multi-level patterns (Colgate Total and Oral-B Advantage). The study used a
      previously reported in vitro model for determining interproximal penetration of
      manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic
      the in-use characteristics of toothbrushing, this model is based on analysis of
      videotaped consumer brushing habits, tooth morphology, and in vivo plaque
      tenacity characteristics, and uses the three most predominantly used brushing
      techniques (circular, up-and-down, and back-and-forth with the brush held at both
      45 degrees and 90 degrees to the tooth surface). In addition, the model's brush
      stroke length, brush force, and brush speed are likewise based on an analysis of
      consumer brushing patterns. The results of this study indicate that the Improved
      Crest Complete with longer rippled outer bristles provided significantly superior
      (p < 0.05) interproximal penetration overall and at the gumline than the Colgate
      Total and Oral-B Advantage brushes.

PMID- 9238887
TI  - A six-month clinical evaluation of the Dentrust toothbrush.
AB  - Clinical study guidelines have been established by the American Dental
      Association for assessing plaque and gingivitis reductions with chemotherapeutic
      agents. Two six-month studies are required. While the toothbrush is also
      instrumental in plaque and gingivitis reduction, there are currently no study
      requirements by the ADA for manual brush efficacy. It was thought to apply the
      long-term efficacy requirements for chemotherapeutic agents to two manual
      toothbrushes to assess their efficacy for comparative purposes. Forty-eight
      subjects using the Dentrust toothbrush and forty-five subjects using the Oral-B
      toothbrush completed a six-month study to assess safety, plaque removal and
      gingivitis reduction. The subjects were randomly assigned to use either the newly
      designed (three sided) Dentrust toothbrush or the traditional flat-headed
      toothbrush. The subjects took their respective toothbrushes home following a
      baseline evaluation, and were subsequently assessed at three and six months by
      the same examiners with the same indices in this single-blind trial. There were
      no significant differences between the two groups on plaque removal during the
      study. At six months, the Dentrust group removed a significant amount of both
      buccal and lingual plaque and the flat-headed toothbrush removed a significant
      amount of buccal plaque only. On gingivitis the groups had no significant
      differences at baseline; however, by six months the Dentrust group was
      significantly better than the flat-headed toothbrush on gingivitis reduction.
      Long-term use of the Dentrust toothbrush can be said to significantly contribute
      to gingival health overall, and especially in the hard to reach lingual areas
      compared to long-term use of a traditional flat-head toothbrush.

PMID- 9238888
TI  - Clinical and laboratory evaluation of powered electric toothbrushes: review of
      the literature.

PMID- 9238889
TI  - Clinical and laboratory evaluation of powered electric toothbrushes: in vivo
      determination of average force for use of manual and powered toothbrushes.
AB  - Mechanical oral hygiene instruments are intended to aid in the removal of stain
      and dental plaque from tooth surfaces. Certain home hygiene procedures, however,
      can lead to soft and hard tissue trauma. Power assisted brushing instruments are
      gaining in popularity, yet there is limited information on the interaction of
      these home care instruments with commercial dentifrices, and the resultant impact
      on oral tissues. In this study, the average forces applied during in vivo
      toothbrushing were determined for three powered brushing instruments (Rota-dent,
      Interplak and Braun Oral-B Plaque Remover) and a manual toothbrush (Oral-B P40).
      The Rota-dent instrument was found to be used with the lowest brushing pressure
      followed, in order, by the Braun Oral-B Plaque Remover. Interplak and the manual
      toothbrush. The average amount of dentifrice applied to the three powered brush
      heads was directly related to the size of the head, with Rota-dent typically
      receiving the least and Interplak the most applied dentifrice.

PMID- 9238890
TI  - Clinical and laboratory evaluation of powered electric toothbrushes: laboratory
      determination of relative abrasion of three powered toothbrushes.
AB  - Previously established data on average forces applied to various brushing
      instruments during in vivo toothbrushing were incorporated into a laboratory
      abrasion model. The apparatus included a specially constructed and standardized
      brushing machine and utilized an acrylic resin substrate. Three powered brushing
      instruments (Rota-dent, Interplak and Braun Oral-B Plaque Remover) and a manual
      toothbrush (Oral-B P40), were compared in this model. The system demonstrated
      excellent precision and could distinguish between brushing instruments with as
      little as 10% difference in abrasivity. It was found that brushing abrasivity
      increased in the order of Rota-dent < Braun < Interplak.

PMID- 9238891
TI  - Clinical and laboratory evaluation of powered electric toothbrushes: laboratory
      determination of relative interproximal cleaning efficiency of four powered
      toothbrushes.
AB  - The clinical brushing data from the paper entitled, Clinical and Laboratory
      Evaluation of Powered Electric Toothbrushes: In Vivo Determination of Average
      Force for Use of Manual and Powered Toothbrushes, by Boyd et al. in this Special
      Issue, were incorporated into a laboratory cleaning model. Utilizing a
      standardized brushing machine and a methyl methacrylate substrate, four powered
      brushing instruments were tested for cleaning efficiency: Rota-dent. Braun Oral
      B. Interplak and Sonicare, and a manual toothbrush (Oral-B P40). The Sonicare
      powered brushing instrument was tested at the manufacturer's recommended brushing
      force of 0.5 N as well as a calculated force of 1.0 N. The results showed that
      the Rota-dent was more efficient (p < 0.01-0.001) in removing stain from both
      flat and interproximal surfaces than any of the other tested brushes. These
      results, together with those reported by McLey, et al. in Clinical and laboratory
      Evaluation of Powered Electric Toothbrushes: Laboratory Determination of Relative
      Abrasion of Three Powered Toothbrushes in this Special Issue, demonstrate that
      the rotary action Rota-dent instrument has the most efficient combination of low
      abrasion and high cleaning efficiency of the four powered brushes and the manual
      brush when all instruments were tested using clinically documented pressures.

PMID- 9238892
TI  - Clinical and laboratory evaluation of powered electric toothbrushes: relative
      degree of bristle end-rounding.
AB  - Toothbrush bristles with sharp edges have been postulated to represent a greater
      threat to dental tissues than end-rounded bristles. This study evaluated the
      effect of both in vivo and laboratory use on bristle wear rate, tip geometry and
      in vitro abrasivity. Three soft manual brushes (Oral-B P40, Crest Complete and
      Butler GUM) and one powered brush (Rota-dent) were tested. The results of this
      study show that the wear rate varied directly with brushing load and amount of
      dentifrice, and inversely with bristle diameter. Despite the initial geometry, a
      flat tip with rounded rims was typically observed after only 30 minutes of manual
      or Rota-dent brush use. There was no statistical difference in in vitro abrasion
      for new brushes versus used brushes.

PMID- 9238893
TI  - Clinical and laboratory evaluation of powered electric toothbrushes: comparative
      efficacy of two powered brushing instruments in furcations and interproximal
      areas.
AB  - The purpose of this study was to compare the efficacy of two powered brushing
      instruments (Rota-dent, Pro-Dentec Inc. and Interplak, Bausch and Lomb Inc.) for
      control of plaque and gingivitis in interproximal spaces and furcations. Thirty
      five patients, randomly selected from a pool of post-active therapy, periodontal
      surgical cases, completed this study. A split-mouth design was utilized in this
      twelve-week trial with each patient acting as his/her own control. Subjects
      alternately brushed one-half of their mouths with each of the instruments: a
      crossover in the brushing pattern occurred at six weeks. Single-blind clinical
      assessments were made by a calibrated investigator at baseline, six and twelve
      weeks. Gingival Index (GI), Plaque Index (PI) and Papillary Bleeding Index (PBI)
      were determined in interproximal and furcation areas. Mean percent reductions
      from baseline for GI, PI and PBI at the end of twelve weeks were 72%, 61% and
      70%, respectively for the Rota-dent, and 46%, 43% and 27%, respectively for the
      Interplak. One-way analyses of variance (ANOVA) and co-variance (ANCOVA) indicate
      that the Rota-dent was significantly more effective (p < 0.001) than the
      Interplak in controlling plaque and gingivitis in furcation and interproximal
      areas with clinically relevant differences in all indices measured.

PMID- 9238894
TI  - Tartar control: assessment of patient benefits and professional scaling
      advantages.

PMID- 9238895
TI  - Instruments and methods for the quantitative measurement of factors affecting
      hygienist/dentist efforts during scaling and root planing of the teeth.
AB  - Manual calculus debridement through scaling accounts for a significant proportion
      of hygienist efforts in dental and periodontal practices. Despite this, little is
      quantitatively known concerning the effects of instruments, technique and
      treatments on debridement (scaling) efficiency or efficacy. The total work effort
      expended by therapists in calculus debridement results from the sum of the
      efforts associated with each scaling stroke. Each scaling stroke, in turn, is
      affected by a variety of physical forces, including those in the control of the
      therapist and those intrinsic to the calculus substrate. The development of
      procedures and treatments to facilitate easier calculus removal requires
      consideration of the physical and technique-related factors which contribute to
      hygienist effort. Instruments have recently been developed which can
      quantitatively measure force dynamics associated with scaling procedures,
      including both therapist-applied forces and forces developed due to the extreme
      hardness and tenacity of supra- and subgingival calculus deposits. The scaling
      instrument developed to quantitatively record developed forces in scaling, the
      Quanticalc, can be used for the assessment of techniques and treatments which can
      soften calculus, facilitating easier debridement. The device can also be used to
      instruct therapists on factors contributing to surface roughness and tactile
      response to these factors. The scaling instrument developed to quantitatively
      measure therapist applied forces in scaling, the Zappa device, can be used for
      assessment of techniques which can increase the efficiency of calculus removal
      with minimal damage to sound root substance. In this paper, the force dynamics
      associated with manual scaling procedures of dental professionals are defined.
      These force dynamics account for the total work expended by hygienists and other
      professionals in the important task of calculus removal. Using this as a
      foundation, the design, use, calibration and clinical applications of these newly
      developed scaling-force measurement systems are described.

PMID- 9238896
TI  - Crest Tartar Control benefits assessed by Quanticalc: clinical method and three
      month results.
AB  - In this paper, a method is described for applying the Quanticalc (QC) dental
      scaler to the clinical assessment of tartar control dentifrice effects on
      supragingival calculus formation and therapist efforts required in subsequent
      calculus debridement. In a 3-month, randomized cross-over study, subjects using
      Crest Tartar Control were observed to form 25% less calculus than they formed in
      a similar period using Crest Regular non-tartar control dentifrice as placebo. QC
      measurements likewise revealed 25% savings in the developed force used to scale
      the anterior lingual surfaces, coupled with a 27% reduction in the number of
      strokes required to clean these surfaces free of supragingival calculus in
      subjects using tartar control dentifrice. The quantitative savings in
      professional effort amounted to 3 kg (developed forces saved) per subject using
      tartar control dentifrice. White subjects using placebo dentifrice for 3 months
      developed less calculus than shown at baseline (29% less calculus), this was not
      complemented by decreases in total force and strokes used in cleaning. This
      supports the hypothesis that the surface area coverage of calculus (e.g., the
      planimetric "area" of supragingival calculus on the tooth) does not contribute
      alone to the amount of effort as forces and strokes required in subsequent
      debridement. These results demonstrate that: 1) the QC dental scaler can be
      effectively used in the clinical assessment of scaling forces/efforts associated
      with supragingival calculus debridement; and 2) a tartar control dentifrice
      containing soluble pyrophosphate is clinically effective in reducing both the
      surface coverage of calculus and the therapist effort required in subsequent
      calculus debridement.

PMID- 9238897
TI  - Quanticalc assessment of the clinical scaling benefits provided by pyrophosphate
      dentifrices with and without triclosan.
AB  - The Quanticalc (QC) dental scaler permits a quantitative assessment of the work
      used by professionals in calculus removal through the measurement of force
      dynamics and scaling strokes applied in calculus debridement. The purpose of this
      study was to use the QC to compare the clinical effects of two 5% pyrophosphate
      dentifrices on dental calculus in subjects following six-months' product use.
      Three-hundred forty-six subjects participated in a six-month, double-blind tartar
      control clinical trial involving traditional Volpe-Manhold Index (VMI)
      evaluations. Following the six-month VMI examinations, the subjects had a QC
      prophylaxis (scaling force measurements). The three dentifrice treatment groups
      included a control dentifrice (NaF only, Crest); NaF dentifrice containing 5.0%
      pyrophosphate (Crest Tartar Control); and NaF dentifrice containing 5.0%
      pyrophosphate plus 0.28% triclosan (antimicrobial). Subjects were balanced by
      baseline (pretest) VMI scores at the start of the trial. QC examinations revealed
      statistically significant reductions in total force and stroke number used by the
      therapist to scale the six anterior VMI teeth for subjects using the
      pyrophosphate tartar control dentifrices as compared to control dentifrice. The
      reduction in scaling effort amounted to almost 3 kg per scaling for subjects. QC
      results paralleled VMI reductions of calculus on the teeth and demonstrated that
      the use of 5% pyrophosphate dentifrices, with or without triclosan antimicrobial,
      results in significant reductions in the total (developed) force and strokes
      required by therapists in regular calculus debridement at a six-month interval.
      The clinical benefits of tartar control toothpastes may not only include
      reductions in cosmetically objectionable supragingival calculus, but in reducing
      professional effort in calculus debridement during regular prophylaxis.

PMID- 9238898
TI  - Effects of a scaling gel on forces developed in debridement of supragingival
      calculus determined by means of a transducer-modified dental scaler: the
      Quanticalc.
AB  - The efficacy of a calculus scaling gel, SofScale (Dentsply, York, PA), has been
      examined in two protocols by the measurement of scaling forces developed in
      supragingival calculus debridement from the anterior dentition using hand scaling
      with a transducer-modified dental scaler, the Quanticalc. In one protocol, the
      effects of the scaling gel were compared to a placebo gel composed of
      conventional toothpaste in a double-blind, split-mouth design. In another
      protocol, the effects of the scaling gel were determined in comparison to non
      treated calculus. Results demonstrated that the scaling gel had no apparent
      effects on the physical forces (work) involved in calculus removal. These results
      suggest that the application of the scaling gel provides no quantitative benefits
      in facilitating calculus debridement during manual tooth scaling.

PMID- 9238899
TI  - A Quanticalc clinical comparison of professional efficiency in manual
      supragingival calculus debridement.
AB  - The Quanticalc (QC) dental scaler permits the assessment of work effort expended
      by professionals in removing supragingival calculus from the teeth. The purpose
      of this study was to compare the efficiency of two professionals in scaling
      calculus under controlled clinical conditions in like populations. One-hundred
      and thirty-one subjects were randomly assigned to two professionals, A and B, for
      QC scaling of their six Volpe-Manhold Index (VMI) teeth. VMI assessments were
      carried out by a separate examiner prior to QC cleaning. The QC was used to
      record total developed force, total strokes and force/stroke used in calculus
      debridement. Results demonstrated significant differences in scaling efficiency
      between the two professionals. These results further demonstrate the potential
      utility of the QC and like devices in assisting in the instruction of
      professionals toward the development of more efficient manual scaling procedures.

PMID- 9238900
TI  - The comparative efficacy of two commercial tartar control dentifrices in
      preventing calculus development and facilitating easier dental cleanings.
AB  - Tartar control dentifrices have been proven effective in reducing the build-up of
      supragingival calculus deposits between professional tooth cleanings. In addition
      to providing consumers with a cleaner dentition, these formulations can, in
      principle, contribute to easier professional tooth cleaning. Until recently,
      clinical methods for evaluating the effects of tartar control dentifrices were
      limited to the assessment of area coverage of calculus on the tooth surface. The
      development of the Quanticalc dental scaler permits the quantitative clinical
      measurement of force and stroke number associated with supragingival calculus
      debridement. In this clinical study, two commercial tartar control dentifrices,
      one containing 5.0% pyrophosphate as the tartar control agent and the other
      containing a combination of 1.3% pyrophosphate and 1.5% Gantrez copolymer, were
      compared for efficacy in reducing the development of supragingival calculus
      between prophylaxes, and in facilitating easier calculus removal in subsequent
      scaling. Results showed that the two commercial dentifrices were equally
      effective in reducing calculus extent between prophylaxes. In contrast, the 5.0%
      pyrophosphate dentifrice was observed to be almost twice as effective on a
      percentage basis as the lower dosage pyrophosphate dentifrice in facilitating
      easier calculus removal. The enhanced activity of the 5.0% pyrophosphate
      dentifrice may be postulated to be due to elevated dosage of tartar control
      crystallization inhibitor or to potential side effects of copolymer in the other
      commercial dentifrice. Importantly, these results substantiate that the clinical
      benefits of tartar control dentifrices are not completely described by actions in
      reducing calculus build-up as assessed by VMI, and that important clinical
      benefits and differences in efficacy may be provided by these formulations in
      facilitating easier dental cleaning of supragingival calculus.

PMID- 9238901
TI  - Nurses' roles are more important than ever in unpredictable practice environment.

PMID- 9238902
TI  - Back to the future in nursing?

PMID- 9238903
TI  - Patients' perceptions of why, how, and by whom dialysis treatment modality was
      chosen.
AB  - OBJECTIVE: The purpose of this qualitative study was to elicit patients'
      perceptions of why, how, and by whom their dialysis treatment modality-
      hemodialysis or continuous ambulatory peritoneal dialysis (CAPD)--was chosen.
      DESIGN: The study design utilized a naturalistic method of inquiry employing a
      qualitative approach. The research was guided by the life-death decisions in
      health care framework developed by Degner and Beaton and the Neuman Systems
      Model. SAMPLE/SETTING: Twenty-two informants were recruited from inpatient and
      outpatient renal dialysis units at a large urban tertiary care center on the east
      coast of the United States. METHODS: Data were collected by individual, focused,
      semi-structured in-depth interviews. RESULTS: A grounded theory, "Patient's
      Choice of a Treatment Modality versus Selection of Patient's Treatment Modality"
      emerged from the data provided by the informants. The theory consisted of 11
      themes that addressed the why, how, and by whom of decision-making: self
      decision; access-rationing decision; significant other decision; to live
      decision; physiologically dictated decision; expert decision; to-be-cared-for
      decision; independence verses dependence decision; no patient choice in making
      decision; patient preference/choice; and switching modalities due to patient
      preference/choice. CONCLUSION: The themes reflected two patterns of decision
      making: the patient and/or significant other chose the treatment modality, and
      the treatment modality was selected because of clinical or practical
      circumstances.

PMID- 9238904
TI  - Quality of life of individuals with end stage renal disease: perceptions of
      patients, nurses, and physicians.
AB  - OBJECTIVE: The objectives of this study were to describe the perceptions of
      physicians, nurses, and patients regarding the quality of life (QOL) of
      individuals with end stage renal disease (ESRD), to identify differences in
      ratings of QOL, and to identify predictors of perceptions of QOL for each group.
      DESIGN: A cross-sectional, descriptive comparative design was used. Three
      measures of QOL, the Self-Anchoring Striving Scale, Index of Well-Being, and Time
      Trade-Off were used. SAMPLE/SETTING: The subjects included 215 patients with ESRD
      (including dialysis and transplant), and 42 nurses and 7 physicians who cared for
      them. All were from a major tertiary care hospital renal program in western
      Canada. METHODS: Patients were interviewed and asked to complete questionnaires
      relating to quality of life, health status, functional status, outlook, support,
      medical, and demographic characteristics. Three measures of QOL, the Self
      Anchoring Striving Scale, Index of Well-Being, and the Time Trade-Off were used.
      Primary physicians and nurses were asked to complete the same questionnaires
      within one week of the patients. RESULTS: It was found that there were
      significant differences in the ratings among the groups. The nurses' ratings of
      patients' QOL were significantly lower than were patients (T2 = 21.89, df = 5,
      377, p < .001). Physicians' mean ratings were higher than patients' ratings (T2 =
      14.24, df = 5, 338, p < .05). Correlations among patients', nurses', and
      physicians' ratings of QOL ranged between .19 and .49. It was also found that
      different variables explained the perceptions of each group regarding the
      patients' QOL. CONCLUSIONS: In this study, nurses, physicians, and patients rated
      the QOL of individual patients differently, and different factors explained the
      perceptions of QOL of each group. Although findings of the study are not
      generalizable, it may be advisable for nurses to be aware that patients and
      physicians may not share their perceptions of patients' QOL.

PMID- 9238905
TI  - Continuous venovenous hemofiltration: a cost-effective therapy for the pediatric
      patient.
AB  - The authors were surprised to discover that at Riley Hospital for Children the
      cost of continuous venovenous hemofiltration (CVVH) constitutes a small fraction
      of the total admission costs, even when it is performed for a large portion of
      inpatient stays. A reasonable treatment that gives critically ill children
      reasonable chances of surviving at reasonable costs, must be considered cost
      effective. CVVH currently offers some pediatric patients an additional chance at
      survival without an extraordinary increase in total hospital bills. Further
      research regarding patient selection, timing of initiation of therapy, and
      improving outcomes is recommended.

PMID- 9238906
TI  - The pediatric nephrology nurse as clinical care coordinator.
AB  - The discipline of pediatric nephrology addresses a wide range of conditions of
      varying severity. The most benign conditions include orthostatic proteinuria, and
      thin basement nephropathy. The most challenging diagnosis in the field is chronic
      renal failure, particularly if the patient is an infant. Nurses trained in
      pediatric nephrology provide care to this entire spectrum of patients within the
      context of their family. The varied responsibilities and specialized training of
      the pediatric nephrology nurse as described in this article can serve as a
      prototype for the independent role of clinical care coordinator.

PMID- 9238907
TI  - Crit Line: instrument to aid fluid removal during hemodialysis.
AB  - Treatment goals were achieved through a combination of approaches. Successful
      outcomes were due to: (a) active interest of the nursing staff in learning and
      applying new treatment concepts and technology, (b) cooperation and input from
      physician staff, and (c) positive response from the patient and a willingness to
      participate in this effort. This methodology is definitely a tool that needs more
      widespread usage and documentation of outcomes, not only patient-centered, but
      staff, physician, and financial usage data as well.

PMID- 9238908
TI  - Central venous catheter site care: chlorhexidine vs. povidone-iodine.

PMID- 9238909
TI  - Cognitive function in dialysis patients. Case study of the anemic patient.
AB  - Impaired cognitive function, a common morbidity associated with end-stage renal
      disease (ESRD), can hinder a patient's ability to work with the dialysis team and
      live well. A combination of adequate dialysis and correction of anemia with
      Epoetin alfa can mitigate the neurobehavioral syndrome associated with ESRD and
      lead to improved cognition. In the presence of suspected cognitive impairment,
      nursing management should emphasize techniques that provide individualized,
      innovative, and ongoing reinforcement of treatment goals and outcomes to improve
      patients' overall quality of life.

PMID- 9238910
TI  - "Every patient deserves a nurse:" cliche or commitment?

PMID- 9238911
TI  - The enrolled nurse role must be supported.

PMID- 9238912
TI  - Developing the role of clinical child health nurses.

PMID- 9238913
TI  - Nutrition and the hospitalized patient: implications for nurses.
AB  - This article, in response to the recent report by the Association of Community
      Health Councils (CHCs) England and Wales 'Hungry in Hospital', explores nutrition
      in the hospitalized patient. Nutrition is instrumental to health and perhaps,
      more importantly, III health. CHCs have a statutory responsibility to monitor the
      delivery of health care on behalf of the general public. It is suggested that the
      issue of nutrition in hospitals is of concern and that there are numerous factors
      which contribute to this. However, this aspect of patient care is not identified
      as the specific responsibility of hospital staff. Nurses should play a pivotal
      role in preventing malnutrition in hospital but, in most cases, they do not. The
      article concludes with a set of recommendations to improve the nutritional status
      of patients and stresses the importance of health professionals listening to
      patients' views.

PMID- 9238915
TI  - Nurses' documentation of infection control precautions: 2.
AB  - A small action research study was undertaken, using a quasi-experimental
      approach, to establish to what extent infection control advice was documented and
      to assess the effectiveness of the provision of an example care plan for control
      of infection. The study population comprised two groups of patients colonized or
      infected with ALERT organisms and involved 28 wards in six hospitals. Baseline
      data confirmed that infection control precautions were documented for less than
      25% of patients overall. Provision of an 'example' care plan, together with
      guidance in its use, was followed by an increase in documentation for all items
      audited, while identification of the infection in the care plan showed a
      statistically significant increase (P < 0.05). However, in spite of this apparent
      improvement the documentation of appropriate care for control of infection
      remained inadequate. It is concluded that, while various strategies to effect
      change are at the infection control nurse's disposal, the need to integrate
      infection control with practice must be addressed at every level to include
      managers, educators and practitioners.

PMID- 9238914
TI  - Olive oil and the Mediterranean diet: implications for health in Europe.

PMID- 9238917
TI  - Children's nursing in Russia: the future generation of professionals.
AB  - Nurses in Russia are trained by doctors who continue to define nurses' role after
      qualification. A children's hospital in Moscow, assisted by workers from a
      British charity, the Tushinskaya Children's Hospital Trust, is currently
      attempting to give nurses more autonomy and control. The project focuses on the
      examination and delivery of nursing care within the context of the Russian
      healthcare system. The aim of the project is to improve the holistic care of the
      hospitalized child and his/her family. Healthcare workers receive training in
      family-centered care, the emotional care of the child, interpersonal skills and
      infection control. Teachers, in conjunction with a Moscow medical school, run a
      course in paediatric nursing. A formal evaluation of the project is difficult
      because of the cultural differences in the measurement of quality. However, there
      are plans to use a model ward which was set up by Russian and British colleagues
      at the Tushinskaya Children's Hospital as an example of good practice to other
      hospitals in Moscow.

PMID- 9238916
TI  - Development of an introductory course in child protection.
AB  - The maltreatment of children is a significant public health and social problem.
      Healthcare professionals have a crucial role to play working with other agencies
      to protect children from abuse and neglect. The need for training, support and
      clinical supervision in this work has been identified. This article discusses the
      collaborative work that led to the establishment of an introductory course in
      child protection (English National Board 970) at one school of nursing and
      midwifery and outlines the benefits of undertaking such a course. The course has
      attracted participants from a range of healthcare settings and has proved to be
      well evaluated and oversubscribed. Practitioners have returned to their work
      setting with increased awareness of child maltreatment and an understanding of
      the need for a proactive approach to child protection.

PMID- 9238919
TI  - Developing a concept analysis of autonomy in nursing practice.
AB  - This article presents a concept analysis of autonomy and offers some insights
      into the quest for and operationalization of autonomous nursing practice.
      Recommendations are made regarding automony and nursing practice at the level of
      the individual practitioner. This concept is also examined in relation to the
      context in which nursing care is delivered. The conclusions drawn as a result of
      this analysis serve as a focus for debate on the challenges that nurses and those
      involved in their education face.

PMID- 9238918
TI  - Efficacy of cardiac rehabilitation. 1: A critique of the research.
AB  - This article, the first of two parts, suggests that cardiac rehabilitation has
      two primary foci: the reduction of morbidity and mortality, and the amelioration
      of distress associated with cardiac pathology. While exercise programmes figure
      prominently in cardiac rehabilitation, empirical studies attest to their
      relatively modest impact on the recurrence of myocardial infarction. Other
      interventions such as stress management programmes reduce psychological distress
      and increase effective coping mechanisms, but only for a limited period.
      Traditional educational programmes compare unfavourably with cognitive
      behavioural interventions. Empirical research appraising the efficacy of many
      cardiac rehabilitation interventions are tainted by numerous design problems. The
      second part of this article considers research into the efficacy of smoking
      cessation and type A behaviour modification programmes.

PMID- 9238920
TI  - Medical investigations. 6: Bone marrow aspiration.

PMID- 9238921
TI  - Nurse occupational stress research. 2: Definition and conceptualization.
AB  - This article commences with the view that appropriate and clear definitions and
      conceptualizations of nurse stress are central to meaningful nurse stress
      research and management. Stress definitions are examined using psychology and
      nursing literature. The conclusions drawn suggest that, sadly, too many reports
      on nurse stress fail to make clear the theoretical underpinning, working
      definitions and conceptualizations of the studies reported. Many studies, in
      defining stress, causation and stress management fail to acknowledge the
      inextricable links between nurses' (public) work and their private lives. The
      question of what nurse stress research rating scales test is also considered.

PMID- 9238922
TI  - Simon Weston: lessons for rehabilitative care. Interview by George Castledine.

PMID- 9238923
TI  - Generic palliative care.
AB  - There has recently been a move towards generic palliative care with the extension
      of the aims, as specified by the WHO (1) to patients with non-malignant
      diagnoses. Trinity Hospice, London, UK, changed their admissions policy to
      include any patient with a specialist palliative care need from January 1 1995.
      The contents of this brief report were first presented as a poster at the EAPC
      Conference, Barcelona, December 1995.

PMID- 9238924
TI  - Cancer support groups--are they effective?
AB  - Cancer causes significant emotional distress to a considerable majority of
      patients. Many of these patients typically receive little formal psychological
      intervention. Support groups, however, have provided one forum from which
      patients can attempt to gain help and can use to overcome some psychological
      trauma that accompanies the cancer diagnosis, subsequent treatment and relapse.
      This article reviews past studies of professionally run cancer support groups as
      opposed to psychological intervention groups. These studies are considered in
      light of the proposed benefits and the methodological limitations frequently
      inherent in such studies.

PMID- 9238925
TI  - Recent developments in adjuvant chemotherapy for colorectal cancer.
AB  - Recent developments in the use of systemic chemotherapy and intraportal
      chemotherapy in the treatment for colorectal cancer suggests that a reduction in
      mortality is achievable. This paper provides an overview of the management of
      colorectal cancer and the rationale behind adjuvant chemotherapy. A review of the
      current research literature published from both America and Europe will follow.
      Finally, the limitations and implications of the reviewed data will be discussed.

PMID- 9238926
TI  - A critique of the methodology of research studies evaluating massage.
AB  - This review examines 14 research studies which have been undertaken to evaluate
      massage. The review offers a critique of the methodology of these studies, and
      issues relating to the research design, samples, measurement tools, analysis and
      the massage intervention are discussed. The critique highlights several key
      issues relating to the design of the studies and concludes with some
      recommendations for future research studies evaluating massage.

PMID- 9238927
TI  - The Lead Lecture as an adjunct to experiential learning (an appropriate modality
      for the introduction of issues related to death, loss and change).
AB  - Issues related to grief in response to loss and developmental changes are of
      significance to palliative care cancer nurses. This paper is essentially an
      educational debate although the issues effect all who concerned with palliative
      cancer care nursing. It reviews selected literature related to the lecture method
      of teaching. The author makes a case for using the Lead Lecture approach with
      experiential learning. It is considered an appropriate means through which to
      introduce palliative nurses to sensitive issues intimately connected to grief.
      The author explores experiential and student centred methods of learning,
      concluding that we should approach them with a certain amount of caution; we can
      expose the learner to too much too soon. The central recommendation of the paper
      is for an integrated approach, harnessing the potential of group led tutorials
      and clinical supervision. An outline seminar plan provides a conceptual route
      map.

PMID- 9238928
TI  - Killing and caring: is euthanasia incompatible with care?
AB  - The issue of euthanasia continues to be surrounded by controversy, particularly
      in relation to its moral status and more recently, the significance that health
      professionals should attach to the principle of respect for patient autonomy.
      Increasing knowledge and expertise in the field of palliative care has also led
      to claims that the provision of effective palliative care services render
      discussion about the introduction of euthanasia unnecessary. By reviewing and
      analysing the arguments put forward in support of the continued ban on voluntary
      active euthanasia, this paper suggests that these arguments largely fail to
      address the notion of patient autonomy and concludes that even with provision and
      access to palliative care service, euthanasia could be considered a moral option
      which is not necessarily incompatible with care.

PMID- 9238929
TI  - Nasogastric and percutaneous endoscopic gastrostomy feeding in head and neck
      cancer patients receiving radiotherapy treatment at a regional oncology unit: a
      two year study.
AB  - The aim of this prospective two year study was to compare the outcome of two
      methods of nutritional support, namely nasogastric [NG] and percutaneous
      endoscopic gastrostomy [PEG] feeding implemented for head and neck cancer
      patients unable to maintain their nutritional status whilst receiving
      radiotherapy treatment at a regional oncology unit. The nutritional requirements
      of the 100 patients included in the study were calculated and an enteral feeding
      regime implemented to ensure the nutritional requirements of each individual
      patient were met. Any changes in the weight and body mass index [BMI] of each
      patient during the study period were documented. The method of delivery,
      composition of feed and duration of nutritional support of each feeding method
      were determined. The feeding methods were found to be equally effective at
      maintaining body weight. Patients with NG tubes in situ were more frequently
      prescribed a standard 1 kcal/ml feed administered via an enteral feeding pump,
      whereas patients with PEG tubes in situ were more frequently prescribed a high
      energy 1.5 Kcal/ ml feed administered by the bolus method. A number of advantages
      are associated with PEG feeding including greater mobility, cosmesis and quality
      of life. Evidence indicates the outcome of radiotherapy treatment is not as
      favourable if interrupted, therefore, it is essential PEG tubes are sited prior
      to commencing treatment, illustrating the necessity for dietetic intervention for
      every patient to be addressed and incorporated into the treatment plan on
      diagnosis of head and neck cancer before definitive management commences.

PMID- 9238930
TI  - Is it worth the wait? A survey of patients' satisfaction with an oncology
      outpatient clinic.
AB  - Increasing numbers of cancer survivors and the tradition of long-term follow-up
      in the outpatient clinic has resulted in overcrowded oncology clinics and long
      waiting times. Little is known about patients' perceptions of their clinic
      attendance. This survey of 252 oncology patients investigated patients'
      satisfaction with the clinic, anxiety associated with clinic attendance and the
      strengths and weaknesses of the oncology service. Results demonstrated high
      levels of satisfaction. Far from being perceived as anxiety-provoking, the clinic
      was looked upon as a valuable source of reassurance, 92% of patients reporting
      they were 'always' or 'usually' reassured as a consequence of their visit.
      Qualitative data showed that clinic staff were the most important source of
      satisfaction. Waiting was overwhelmingly the worst aspect of the clinic,
      described by 27% of patients as 'excessively long'. One-fifth of the total sample
      had attended the clinic for 10 years or more and over a third of this group
      reported they would be worried at the prospect of being discharged to the care of
      their general practitioners. Despite disadvantages associated with long waits,
      the clinic was perceived as providing a valuable source of reassurance which a
      proportion of patients were clearly reluctant to be without.

PMID- 9238931
TI  - Patients' experiences of chemotherapy: side-effects of carboplatin in the
      treatment of carcinoma of the ovary.
AB  - There has been little investigation of the side-effects experienced by women
      receiving adjuvant carboplatin in the treatment of ovarian cancer. This study
      aimed to describe the range of problems experienced by patients and to estimate
      incidence and severity of side-effects over the treatment period. Eleven patients
      participated and completed a 75-item self-report questionnaire at each course of
      treatment. Severity of each side-effect was graded from 0 to 4. Patients also
      stated which had been the worst side effect at each course. The response rate was
      94%. Seventy-two side-effects were reported. Fatigue emerged as both the most
      common and the most 'troublesome' side-effect. Nausea, difficulty sleeping, taste
      change, and constipation were also ranked highly. Although limited by a small
      sample size, this study suggests patients undergoing carboplatin experience a
      wide range of problems, many of which merit further investigation.

PMID- 9238932
TI  - Social support and the cancer patient--a need for clarity.
AB  - This paper addresses the importance of social support to the health of cancer
      patients, drawing upon the relevant literature from medical, psychological and
      social research. The development of a measure of social support for cancer
      patients for use in guiding health care and assessing the effects of social
      support on the patients health statues are needed. Various definitions of social
      support are considered and the difficulties of adequately defining the concept
      are discussed. Given the lack of a uniformed definition and emphasis on multiple
      aspects of social support it is argued that research should address the
      experiences and needs of patients with cancer. Specifically, with a view to
      providing a clinical measure of social support. The development of the Bottomley
      Social Support Scale is outlined and suggestions made for ways forward in
      researching and understanding social support.

PMID- 9238933
TI  - Qualitative research: exploring new frontiers.
AB  - Qualitative research is an excellent strategy for exploring new areas of study.
      It is particularly appropriate for the field of gastroenterology nursing, a
      developing nursing specialty. In this article, the authors provide an
      introduction to qualitative research through a comparison of quantitative and
      qualitative perspectives, exploration of qualitative research designs, and
      discussion of qualitative analysis. Examples of qualitative research are used to
      illustrate the rich, vivid, and practical information gained using four different
      mehtodological approaches. Qualitative research topics appropriate for
      gastroenterology nurse researchers are suggested.

PMID- 9238934
TI  - Celiac disease: helping families adapt.
AB  - Lifelong dietary compliance prevents the long-term effects associated with celiac
      disease. However, this simple solution, diet, has many long-reaching effects on
      the children affected with celiac disease and their families. Assisting families
      in coping with this chronic illness is necessary for children and families to
      develop a sense of control. An overview of celiac disease is presented through
      the use of a case study. Guidelines are given to enable the healthcare provider
      to understand and help families through the process of adapting to a child with a
      chronic illness. Recommendations for nutritional management with helpful
      suggestions related to making celiac disease an everyday part of family life are
      discussed.

PMID- 9238935
TI  - Development of the Vulnerability Scale.
AB  - Developing a new data collection scale is a time- and labor-intensive process.
      Initially, the items may be developed from a review of the appropriate
      literature, clinical expertise of the developer, in-depth interviewing of
      potential subjects, or any combination of these techniques. Next, evidence of the
      validity (content-related, construct-related, and criterion-related), internal
      consistency reliability, and reliability of the scale must be established. The
      new scale may be administered to one or two small samples (pilot studies) before
      it is ready for use with a larger group. Gathering evidence regarding the scale's
      validity and reliability with different groups and consequent revision are
      ongoing processes. In this article, the authors describe how this process was
      followed in developing the Vulnerability Scale.

PMID- 9238936
TI  - Perineal skin care for patients with frequent diarrhea or fecal incontinence.
AB  - In this article, the author presents an overview of normal skin and a description
      of perineal skin injury. The focus is to identify the goals for treatment for
      persons with frequent diarrhea or fecal incontinence as it relates to their
      perineal skin care. Specific algorithms for acute care and ambulatory settings
      are defined, and two case studies are presented. The treatment goals include
      evaluation of and recommendations for reviewing and choosing perineal skin
      products.

PMID- 9238937
TI  - Ulcerative colitis: from medical management to ileal pouch anal anastomosis: a
      patient's perspective.
AB  - Ulcerative colitis (UC) is a chronic disease that may require extensive medical
      and, at times, surgical intervention. Patients with UC are encouraged to form a
      multidisciplinary healthcare team to provide the support needed to cope with this
      chronic, debilitating illness. In this article, the authors provide the personal
      perspective of a patient coping with UC, the role of the gastroenterology nurse,
      and the viewpoints of key members of the healthcare team. Tracing the course of
      the disease from onset to medical management and then surgery, the authors relate
      the process by which the patient interacted with the healthcare team to reach the
      decision for seeking a surgical solution to the disease and how the patient coped
      with the rare but extended complications of surgery. The patient's decision
      illustrates the importance of her perspective and the varying roles played by the
      healthcare team. Medical management of UC and the technical aspects of ileal
      pouch anal anastomosis surgery are discussed.

PMID- 9238938
TI  - Risk management scenarios and responses.

PMID- 9238940
TI  - Common vitamin B complex agents and folic acid: Part IV. Leucovorin calcium
      (citrovorum factor, folinic acid [wellcovorin]).

PMID- 9238939
TI  - When a friend is bulimic.

PMID- 9238941
TI  - Using cluster analysis to develop a healing typology in vascular ulcers.
AB  - A clinically meaningful typology of healing was developed to assist nurses in
      assessing patients' healing potential. A descriptive correlational design was
      used to determine similarities in healing characteristics of older people with
      venous, venous-arterial, and arterial leg ulcers (n = 156). Hierarchical
      clustering techniques dendrogram using Ward's method suggested that three
      clusters existed based on the ankle/brachial pressure index, liposclerosis
      (hardening and induration of the skin of the lower limb), edema and wound
      characteristics: thus a healing typology was potentially formed. Nonhierarchical
      techniques such as analysis of variance examined cluster differences for the
      initial ulcer area (p < 0.013) and suggested that these groupings were reflective
      of differing ulcer areas. However, significant differences in the rate of healing
      (difference between ulcer surface area in week 4 and week 1) (measured by
      topographic mapping) group comparisons were not significant at the 0.05 level.
      Clinical differences in the healing rate were apparent, and three individual
      profiles of leg ulcer sufferers based on the three differing clusters of factors
      were outlined: rapid healers, slow healers, and nonhealers. Further research into
      the clustering of these factors and their application to longer healing times or
      time to complete healing may be significant and support the utility of this
      typology.

PMID- 9238942
TI  - Venous ulceration: active approaches to treatment.
AB  - Traditional treatment of venous ulceration has been conservative: elevation,
      wound care, compression, and patient education based on prevention. Conservative
      treatment will heal most ulcers over time: however, the data reflect a 29% to 59%
      recurrence rate with optimal care and follow-up. Recurrent ulceration results in
      significant cost and disability. It is none accepted that limbs with all the
      signs of severe chronic venous insufficiency (CVI) may have a normal deep venous
      system. Patients in whom this is the case can be treated surgically with good
      long-term results. In this article, the specific underlying causes of CVI are
      noted and diagnostic tests are reviewed. The CEAP (clinical signs, etiology,
      anatomy, and physiology) classification system is discussed in terms of
      systematically assessing CVI. Common surgical techniques are related to the
      underlying pathophysiology, and the nursing care of the patient undergoing
      surgical intervention is also discussed. The cause of the condition should be
      investigated, and surgical treatment, when appropriate, should be offered as an
      alternative to the active symptomatic patient with CVI.

PMID- 9238943
TI  - Deep vein thrombosis in pregnancy and the puerperium: a comprehensive review.
AB  - Although uncommon during pregnancy and the postpartum period, deep vein
      thrombosis (DVT) and its sequela, pulmonary thromboembolism, remain leading
      sources of maternal mortality and morbidity. The majority of literature
      concerning DVT in pregnancy and the postpartum period exists in the medical
      journals, with only a small amount in nursing journals. This article provides the
      nursing community a comprehensive review of literature concerning the incidence
      of both DVT and pulmonary embolism in pregnancy and the postpartum period,
      identification of risk factors, the effectiveness of available screening and
      diagnostic tools, and finally, options for treatment and prophylaxis.

PMID- 9238944
TI  - Experience with open-heeled Unna boot application technique.
AB  - One of the most common and effective treatments for venous stasis ulcers (VSUs)
      is the Unna boot dressing (UBD), first described by Unna in the 1890s. No one
      technique for UBD application has been documented by research to be the most
      effective for ulcer healing. This article discusses the open-heeled UBD
      application technique. Twelve patients with 17 VSUs that have been treated with
      the open-heeled UBD application technique are reviewed. The patients were
      primarily treated by the first author. Detailed patient education instructions
      are given. The open-heeled UBD is easier to apply patients are more comfortable
      and can fit into their normal shoewear condition of the heel can be monitored
      while the UBD is in place, and specially trained practitioners can apply UBDs
      with minimal to no compression on patients with concomitant venous arterial
      insufficiency. Ambulatory patients can also maintain greater ankle mobility
      during treatment. This may have important implications for activating the muscle
      pump under compression, which can facilitate blood return and reduce venous
      hypertension while the patient with venous stasis ulcer is ambulatory. The open
      heel method may also allow greater mobility of the ankle that can help prevent
      "frozen" ankles associated with VSUs.

PMID- 9238945
TI  - A forever healing: the lived experience of venous ulcer disease.
AB  - A phenomenological study was conducted to determine the lived experience of
      healing a venous ulcer for patients in an ambulatory surgical clinic. In addition
      to seven tape-recorded, transcribed interviews, weekly participant observations
      were made for 1 year. Interviews and field notes were transcribed and analyzed
      for themes by using van Manen's approach. Four major themes emerged from the
      analysis: (1) "A forever healing process" refers to the extended time over which
      healing occurs. (2) "Limits and accommodations" refers to the patterns of
      limitation related to mobility and activity restrictions due to pain and
      disfigurement. (3) "Powerlessness" describes the resignation about the
      inevitability of wound recurrence. (4) "Who cares?" refers to variation among the
      patients in assuming responsibly for managing their ulcer. Understanding the
      lived experience of venous leg ulcer disease allows care providers to provide
      empathic care. Patients can be encouraged to be active members of the treatment
      team and to assume responsibility for care and lifestyle choices.

PMID- 9238946
TI  - How we eat: an America divided.

PMID- 9238947
TI  - Obesity and weight loss.

PMID- 9238948
TI  - Acute diarrheal illnesses in children.

PMID- 9238949
TI  - Nutrition strategies for adolescents with insulin-dependent diabetes mellitus.
AB  - Optimal metabolic control is a primary management objective for adolescents with
      insulin-dependent diabetes mellitus. Nutrition therapy plays an important role in
      meeting this challenging treatment goal. This article presents broad nutrition
      goals, makes macronutrient recommendations, and describes their effect on blood
      glucose levels. Various meal-planning techniques and other developmentally
      appropriate approaches to assist adolescents in meeting these nutrition
      objectives are described. Finally, challenges in implementing nutrition therapy
      in an adolescent population are discussed.

PMID- 9238950
TI  - Optimizing lipid levels through diet.
AB  - Medical nutrition therapy, consisting of a diet low in saturated fat, has an
      important role in reducing risks for cardiovascular disease and hyperlipidemia.
      Dietary factors that have a negative effect on blood lipid levels include dietary
      cholesterol, saturated fat, and trans fatty acids, whereas unsaturated fats,
      omega-3 fatty acids, and soluble fiber may help lower blood lipid levels. A two
      step approach to medical nutrition therapy can help health professionals counsel
      people with high lipid levels to change their food choices and eating behaviors
      to lower their risk of heart disease. This approach involves teaching the patient
      how to substitute lower-fat foods, read labels, control portions, and use
      healthier cooking techniques. Medical nutrition therapy needs to be
      individualized to help lower the risk of heart disease.

PMID- 9238951
TI  - Diet strategies in the treatment of non-insulin-dependent diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus is a chronic disease frequently treated
      in a primary care setting by health care providers. Despite recent advances in
      the pharmacologic treatment of this disease, the cornerstone of management
      continues to be nutrition therapy. Familiarity with the basic principles of
      dietary management and the recently revised American Diabetes Association
      nutrition recommendations provide a framework for educating patients in the
      primary care setting. Basic components of the diet, including the latest
      guidelines concerning the use of sucrose, carbohydrates, fiber, and mineral
      supplementation, are discussed here. This article also outlines the steps
      necessary to use this information to individualize the dietary prescription.
      Assessment guidelines, intervention strategies, and evaluation methods for
      patient education are reviewed.

PMID- 9238952
TI  - Dietary prevention of osteoporosis.
AB  - Osteoporosis is a major health problem facing women and men, and the number of
      people affected is likely to increase substantially as the population ages. The
      gold standard for treatment has always been prevention. This article reviews
      therapeutic options, with an emphasis on nutrition; outlines current
      recommendations for calcium and vitamin D throughout the life span; and discusses
      food and supplemental sources of calcium. Guidelines are given for identifying
      high- and low-risk patients, and appropriate interventions are highlighted.

PMID- 9238953
TI  - Dexfenfluramine.

PMID- 9238955
TI  - Acute gastroenteritis.

PMID- 9238954
TI  - Irritable bowel syndrome.

PMID- 9238957
TI  - Low-sodium diet.

PMID- 9238956
TI  - Calcium intake.

PMID- 9238958
TI  - Nutrition strategies for adolescents with insulin-dependent diabetes mellitus.

PMID- 9238959
TI  - Patient with bulimia nervosa.

PMID- 9238961
TI  - Benchmarking: best practices.

PMID- 9238960
TI  - Patient with recurrent episodes of hives. Answers and discussion of allergic
      disorders case study.

PMID- 9238962
TI  - The new grassroots.

PMID- 9238963
TI  - The nuts and bolts of enteral infusion pumps.
AB  - Enteral feeding pumps and delivery systems have undergone many changes since
      enteral feedings were first initiated. There are a variety of features available
      in both pumps and delivery sets with exciting developments on the horizon.
      Technologic advances have been designed to meet the changing needs of nurses and
      patients. Careful review of the options will ensure the best fit in terms of
      medical therapy and utilization of resources.

PMID- 9238964
TI  - Care of the patient with Clagett open-window thoracostomy.
AB  - The Clagett open-window thoracostomy is performed to give patients with empyema
      improved quality of life and other outcomes. Adult health nurses care for
      patients undergoing this procedure preoperatively, postoperatively, and at home,
      and must consider several important issues to prevent serious complications and
      facilitate family care.

PMID- 9238965
TI  - Managing unlicensed assistive personnel: tips for improving quality outcomes.
AB  - Today, nursing care delivery requires effective management of unlicensed
      assistive personnel (UAP). With capitation, each member of the care delivery team
      is critical to assuring quality patient outcomes. Yet, staff nurses may not fully
      understand how to maximize the performance of these workers. To be effective
      managers, nurses must understand how learning styles, cultural diversity, and
      multicultural team building improve the performance of UAP and the entire care
      delivery team. These variables are critical elements in effective communication,
      delegation, supervision, behavior modification, and team building with UAP.

PMID- 9238966
TI  - Transitional care: bridging the gap.
AB  - As hospitals redesign into integrated delivery systems, new services and linkages
      to support patients across the care continuum become necessary. The
      implementation and outcomes of a transitional care program are discussed and
      evaluated.

PMID- 9238967
TI  - Using a portable bladder scan to reduce the incidence of nosocomial urinary tract
      infections.
AB  - An innovative technology, BladderScan, was introduced to reduce urinary tract
      infections and care costs in hospitalized adults. Evaluation revealed reductions
      in infection rates and overall benefits exceeding costs.

PMID- 9238968
TI  - Wellness promotion and the elderly.

PMID- 9238969
TI  - Care of the dissociative identity disordered patient on a medical-surgical unit:
      nursing implications.

PMID- 9238970
TI  - Case management in long-term care: challenges, changes, and opportunities.

PMID- 9238971
TI  - Dysphagia article questioned.

PMID- 9238973
TI  - Vision for the future.

PMID- 9238974
TI  - Managing health and cost: everybody's business.

PMID- 9238975
TI  - Care of the patient requiring mechanical ventilation.
AB  - Today patients that are otherwise stable may require mechanical ventilation for
      prolonged periods of time. The medical-surgical nurse may be expected to care for
      these patients in a setting outside the intensive care unit. Basic knowledge of
      the modes of ventilation, assessment, and troubleshooting of ventilators and
      assessment and care of the patient requiring mechanical ventilation are reviewed
      in this article.

PMID- 9238976
TI  - Nutritional needs and support of mechanically ventilated patients.
AB  - Malnutrition is common in patients who are mechanically ventilated. Poor
      nutritional status contributes to impaired respiratory muscle function, lung
      structure, ventilatory response, and resistance to infection. By detecting
      malnutrition in its early stages, carefully calculating energy needs, determining
      appropriate nutrition support, and avoiding nutrition support complications,
      medical-surgical nurses can provide effective nutrition care to mechanically
      ventilated patients. Improved nutritional status is associated with better
      pulmonary function and greater ease in weaning from mechanical ventilation.

PMID- 9238977
TI  - Alcohol withdrawal in a medical-surgical setting: the 'too little, too late'
      phenomenon.
AB  - Alcohol withdrawal within a medical-surgical setting frequently causes management
      problems and negative patient outcomes. The authors describe a multidisciplinary
      withdrawal protocol that addresses risk management and quality of care issues.
      Fewer "Against Medical Advice" discharges and staff assaults, and decreased
      length of stay were reported as a result of the protocol's implementation.

PMID- 9238978
TI  - Medication calculation skills of the medical-surgical nurse.
AB  - Medication administration is one of the most time-consuming aspects of nursing
      practice. Expertise in medication calculation and administration is essential to
      the treatment of all patients; however, many nurses experience difficulty when
      calculating medications. In this study, 56.4% of nurses could not calculate
      medications correctly in 90% of the problems, suggesting the need for regular
      self-testing of medication calculation skills. Continuing education programs
      implemented for identified medication calculation errors influences nursing
      practice and patient care outcomes.

PMID- 9238979
TI  - Identifying and treating femoral artery pseudoaneurysms following invasive
      cardiac procedures.
AB  - Advances in interventional cardiology offer new choices for patients with
      coronary artery disease. Unfortunately, these new procedures are associated with
      complications, such as femoral artery pseudoaneurysms. Accurate and timely
      vascular assessments by adult health nurses can detect this problem and result in
      prompt treatment, sometimes including ultrasound-guided compression.

PMID- 9238980
TI  - Anxiety in liver transplant patients.
AB  - Anxiety is a common symptom experienced by patients recovering from a liver
      transplant. The times of liver biopsy and organ rejection were described by 33
      participants as their most anxiety-producing experiences. This was measured by
      the State-Trait Anxiety Inventory and a visual analogue scale.

PMID- 9238981
TI  - Preparing your program for JCAHO subacute accreditation.

PMID- 9238982
TI  - Understanding strategies for treating HIV.
AB  - A great deal has been learned over the past 1 to 2 years about treatment of HIV
      infection. Viral load testing now provides a reliable method of assessing the
      effectiveness of any treatment regimen. And it is now clear that triple
      combinations of drugs (typically two nucleoside analogues and one protease
      inhibitor) are producing excellent reductions in viral load with concomitant
      elevations in CD4+ counts. This new triple-approach drug regimen has demonstrated
      clear advantage in delaying disease progression in persons in very early or late
      stages of the disease.

PMID- 9238983
TI  - Educating for the community.

PMID- 9238984
TI  - Patient-family-community education: no longer frills.

PMID- 9238985
TI  - Obesity: genetic update and clinical implications.
AB  - One of the nation's most significant health problems, obesity is preventable and
      treatable. By understanding the role genetics plays in obesity, nurses help
      counsel clients to reach and maintain their optimal weight.

PMID- 9238986
TI  - Defining educational settings to improve client health teaching.
AB  - Nurses are better prepared for the changing health care environment if they know
      what composes the educational setting for client health teaching. By
      understanding how organizational, environmental, and clientele factors can be
      used to optimize learning in different settings, nurses can improve teaching
      quality and client outcomes.

PMID- 9238988
TI  - Drug-induced hepatic injury.
AB  - Hepatic injury due to medications and other substances is a serious, life
      threatening condition. Nurses must act to prevent this disorder and identify and
      treat patients who have been exposed to hepatotoxic agents.

PMID- 9238987
TI  - Creating and implementing guidelines on caring for difficult patients: a research
      utilization project.
AB  - Difficult patients challenge the resourcefulness of nurses. Considering the
      results of a focus group study, guidelines are designed for the care of difficult
      patients. Four case studies present the use of the guidelines, including
      interventions and outcomes.

PMID- 9238989
TI  - Environmental heat-related illnesses.
AB  - Environmental heat-related deaths and illnesses in the United States are
      considered preventable. Through proper education, planning, and hydration,
      hundreds of individuals would not succumb to heat-related illness.

PMID- 9238990
TI  - Sleep: linking research to improved outcomes.

PMID- 9238991
TI  - Life support.

PMID- 9238992
TI  - Beyond sulfonylureas: new oral medications in the treatment of NIDDM (type II
      DM).

PMID- 9238994
TI  - Redesigning your career.

PMID- 9238995
TI  - Radiation-induced skin alterations.
AB  - A number of methods of managing radiation-induced skin reactions have been
      presented in this article. However, currently no standard of care exists among
      institutions and physicians in managing these skin reactions. In fact, little
      nursing research has been performed on managing radiation skin reactions. The
      Radiation Therapy Special Interest Group (RTSIG) of the Oncology Nursing Society
      is in the process of developing radiation-induced symptom management research.
      Until these data are available, it is recommended that nurses caring for patients
      with radiation-induced skin reactions focus on educating their patients on basic
      skin care methods (see Figure 5) and consult the patient's radiation oncology
      nurse regarding wound care management.

PMID- 9238996
TI  - The role of nurse practitioners in research.
AB  - Research can be accomplished by NPs even in times of financial constraint.
      Planning becomes more important, and a group of clinicians working together will
      make a difference in making studies possible. The most important requirement is
      probably the need for utmost care in planning. Given that NPs are willing to
      undergo the effort and frustrations of meticulous planning, NPs can fill the gap
      in clinical research left by the concentration of studies at the molecular rather
      the patient level.

PMID- 9238997
TI  - The effect of cancer pain on quality of life in different ethnic groups: a
      literature review.
AB  - Pain influences the quality of life (QOL) of the majority of people with cancer.
      The way that pain is perceived and the way it is dealt with is largely influenced
      by the ethnocultural background of the individuals and families experiencing the
      pain. This article stresses the need for more research by advanced practice
      nurses (APN) into ethnocultural influences and the way these influences will
      affect the care we give and the outcomes of pain management.

PMID- 9238998
TI  - Ko'olauloa: Hawai'i's North Shore nurse practitioner based clinics (Kahaluu'u,
      Hau'ula, Haleiwa, Punalu'u).
AB  - Nurse practitioner-based/Traditional Hawaiian Lomi-Lomi clinics were funded with
      grant money and matching funds to provide medical services to uninsured Native
      Hawaiians. The clinics proved to be successful through the outreach efforts of
      local outreach workers, satisfaction with Lomi-Lomi (Hawaiian massage with a
      spiritual component), and the primary and preventive services of nurse
      practitioners. Western medicine and Lomi-Lomi are practiced in the same clinic
      setting cooperatively. Nurse practitioners refer to other community-based
      programs for nutrition education and weight control and to physicians as needed.
      Nurse practitioners must be aware of administration and fiscal issues to maintain
      such nontraditional clinics and services.

PMID- 9238999
TI  - Community partnership primary care case study: Abbottsford Community Health
      Center.
AB  - Welfare reform and the movement of Medicaid to managed care have set the stage
      for great risk and potential reward for low-income communities and their health
      care providers. Nurse practitioners are responding to current opportunities by
      opening up nurse practitioner-directed practices to offer a range of care to
      targeted high-risk patients and communities. Nursing practices and the
      communities they serve will be greatly strengthened by democratic collaboration
      and partnership. The beginnings of Abbottsford Community Health Center are
      described as an example of community partnership primary care.

PMID- 9239000
TI  - The nurse practitioner and homeless adolescents in Waikiki.
AB  - Staffed by those with advanced skills and training, the nurse practitioner-based
      clinic is in a unique position to offer the street youth primary health care
      designed to meet their basic needs. Within the setting of a "drop-in" program in
      Waikiki, free and confidential medical, educational, and social services are
      offered to homeless adolescents bound to survival on the streets.

PMID- 9239001
TI  - The elderly in nursing homes: a special population.
AB  - This article identifies characteristics that define the elderly in nursing homes
      as a special population. There is a description of the Nurse Practitioner's role
      in providing care to this population.

PMID- 9239003
TI  - The Royal College of Nursing Congress.

PMID- 9239002
TI  - Advanced nursing practice with the Indian Health Service.
AB  - Work with the US Indian Health Service is an exciting and rewarding experience.
      It allows family nurse practitioners the opportunity to use a wide range of
      skills and to develop true family and community involvement.

PMID- 9239004
TI  - Disaster in the making.

PMID- 9239005
TI  - Getting better.

PMID- 9239006
TI  - Infectious incidents.

PMID- 9239007
TI  - Whose body is it, anyway?

PMID- 9239008
TI  - Bullying in the workplace. A survey.

PMID- 9239009
TI  - Right on your side.

PMID- 9239010
TI  - The cost of understaffing.

PMID- 9239012
TI  - Mental health network: risk assessment.

PMID- 9239011
TI  - Index-linked.

PMID- 9239013
TI  - Health visitor support for patients with breast cancer--2.
AB  - In the second of two articles, the author's report on research indicates that
      health visitors (HVs) with preparation and education for the role, can provide
      effective support for patients having treatment for breast cancer in the
      community. A sample of 35 patients with breast cancer was interviewed at home
      soon after referral from hospital following treatment and again three months
      later. They had many medical and psychosocial problems relating to their disease
      and its treatment, indicating need for professional support. Support from HVs
      consisted of preparing patients for treatments, assessing how they were coping
      and liaising with staff from the breast unit. The HVs encouraged patients to
      express their feelings about altered body image, sexuality and depression, as
      well as offering information and medical advice when this was requested. The HVs
      also helped patients with social problems, mainly difficulties with family
      relationships, finance and work. The first article appeared on May 7 1997.

PMID- 9239014
TI  - Pain scoring as a formal pain assessment tool.
AB  - This article describes the introduction of subjective pain scoring as a pain
      assessment tool to the surgical unit of a district general hospital. The author
      highlights the advantages, and explains the actions taken to overcome the
      problems of changing practice through the introduction of a formal pain
      assessment tool.

PMID- 9239015
TI  - A public health approach to nursing in the community.
AB  - This article, the first in a three-part series on public health, promotes the
      case for community nurses to grasp the opportunities a public health approach to
      care offers to populations and communities. The importance of organisation and
      evaluation are emphasised as is the need for support from colleagues which, argue
      the authors, can only be obtained if the benefits of this approach are made
      clear. The second article in the series will appear next week.

PMID- 9239016
TI  - Networking.

PMID- 9239017
TI  - Clinical micronutrition.

PMID- 9239018
TI  - What has happened to the mantra 'free at the point of delivery'?

PMID- 9239020
TI  - Secrets and spies. Interview by Jo Waters.

PMID- 9239019
TI  - Milk of human kindness is back in fashion.

PMID- 9239021
TI  - The devaluation of learning disabilities nurses.

PMID- 9239022
TI  - Behind the smokescreen.

PMID- 9239023
TI  - Nipping the bully in the bud.

PMID- 9239024
TI  - Teetering on the brink.

PMID- 9239025
TI  - Fire up.

PMID- 9239027
TI  - Try it, you might even like it.

PMID- 9239026
TI  - Thousands like us. Interview by Daloni Carlisle.

PMID- 9239028
TI  - All together now?

PMID- 9239029
TI  - Stand and deliver.

PMID- 9239030
TI  - Hot potatoes. Deadly substitute.

PMID- 9239031
TI  - Oil on troubled waters.

PMID- 9239032
TI  - The global challenge.

PMID- 9239033
TI  - Blood coagulation: what screening tests can show.
AB  - As part of series concerning the role of laboratory testing in patient care, this
      article focuses on tests of blood coagulation. These tests are used as first-line
      screenings in the investigation of patients who have an abnormal tendency to
      bleed and to monitor the treatment of those who are receiving anticoagulation
      therapy, most often for the treatment or prevention of deep-vein thrombosis.

PMID- 9239035
TI  - Developing skills for sharing information.

PMID- 9239034
TI  - Nurses' experiences of continuing education.
AB  - This article outlines some of the main findings from a survey into the
      experiences of nurses with continuing professional education following the
      introduction of the UKCC's standards for post registration education and practice
      (PREP). This survey was conducted jointly by the Queen's Nursing Institute and
      Nursing Times.

PMID- 9239036
TI  - Making a difference through acceptance.

PMID- 9239037
TI  - Latex gloves: still a serious occupational hazard.

PMID- 9239038
TI  - Fractured neck of femur. Professional issues.

PMID- 9239039
TI  - Tools of the trade.

PMID- 9239041
TI  - Mind games.

PMID- 9239040
TI  - Spot the saboteurs.

PMID- 9239042
TI  - The recruitment crisis.

PMID- 9239043
TI  - The Hong Kong two-step.

PMID- 9239044
TI  - Red China blues. Interview by Rebecca Coombes.

PMID- 9239046
TI  - Alone again or....

PMID- 9239045
TI  - The call for worldwide regulation of nursing and midwifery.

PMID- 9239047
TI  - Tray of confusion.

PMID- 9239048
TI  - Landing in difficulties.

PMID- 9239049
TI  - You cannot get a quart into a pint pot--not even in the NHS.

PMID- 9239050
TI  - A year of dealing with complaints.

PMID- 9239051
TI  - Critical timing.

PMID- 9239052
TI  - Every breath you take.

PMID- 9239054
TI  - Dreams come true.

PMID- 9239053
TI  - The skill behind the mask.

PMID- 9239055
TI  - Kate's big ideas.

PMID- 9239056
TI  - Caught short.

PMID- 9239057
TI  - The Lariam debate.

PMID- 9239058
TI  - A review of psychosocial family interventions for schizophrenia.
AB  - Research shows the rate of relapse among people with schizophrenia can be reduced
      by interventions focusing on how a family functions. This article is a systematic
      review of the studies, held by the Cochrane Library. The review concludes that
      relapse, hospital admission and compliance with medication were improved where
      family-based interventions were used.

PMID- 9239059
TI  - Reflections on performance.
AB  - This qualitative study looked at the value of appraisal for nurses. It was
      conducted with clinical staff in one health district at a time when the NHS was
      in the middle of the drives towards efficiency and effectiveness. Although
      participants in the study identified ways in which appraisal could help them in
      their work, they also highlighted a culture of suspicion and indifference that
      limited their effectiveness. The findings of the research emphasise the value of,
      and need for, appraisal for nurses, and offer suggestions for methods of ensuring
      success in the enterprise.

PMID- 9239060
TI  - Reflective practice.

PMID- 9239061
TI  - Cushions are important to pressure sore prevention.

PMID- 9239063
TI  - Resume writing and interviewing skills for getting the job you want.
AB  - Getting the nursing position you want is a highly competitive endeavor in today's
      health care environment. Knowing how to market yourself can make the difference
      between being hired and being overlooked. Two crucial elements of a successful
      job search are resume writing and interviewing. The purpose of a resume is to
      pique the interest of the reader and secure a job interview. The interview then
      provides a platform for the candidate to highlight his or her achievements and
      convince the employer that he/she is the best choice for the position. Resume
      development and interviewing must be approached with skill and knowledge. A well
      written resume followed by a well-executed interview gives the candidate a strong
      advantage in obtaining the position he/she wants.

PMID- 9239064
TI  - Toe-to-thumb transplantation.
AB  - Microsurgical techniques have become useful in reconstructive surgery of the
      hand. Toe-to-thumb transplantation currently is the procedure of choice for thumb
      loss reconstruction. For a successful outcome, meticulous planning is imperative
      and presumes a thorough knowledge of the pertinent anatomy and surgical
      technique. The method of thumb reconstruction must be individualized and is
      dependent on the patient's functional needs, age, and the level of thumb
      amputation. Postoperatively, diligent nursing care is essential in assuring a
      positive outcome. Continuous communication between physicians and nurses is
      crucial. Astute monitoring and assessment are the core components of successful
      care.

PMID- 9239065
TI  - A joint protocol for home skeletal traction.
AB  - Cost-effective delivery of quality patient care is a major focus of the
      orthopaedic advanced practice nurse's practice. Long-term skeletal traction
      therapy for select fractures of the pelvis remains a treatment option for certain
      patients. The purposes of this article are to describe the development of a joint
      proposal for home skeletal traction therapy and to analyze the cost savings
      involved by reviewing a case study of a home traction patient.

PMID- 9239066
TI  - Tile classification of pelvic disruption.

PMID- 9239067
TI  - Discharge planning for the patient requiring home intravenous antimicrobial
      therapy.
AB  - Home intravenous (IV) antimicrobial therapy is a well accepted and widely
      practiced form of home infusion therapy. Orthopaedic-related infections, often
      requiring long courses of therapy, are commonly treated in the home setting after
      a brief hospitalization. Hospital orthopaedic nurses play an important role in
      preparing patients for home care. This article addresses patient selection for
      home IV therapy, the discharge planning process, and educational preparation of
      the patient. The role of the home care nurse is briefly presented to enhance the
      orthopaedic nurse's knowledge of the continuum of care.

PMID- 9239068
TI  - Acetaminophen toxicity.
AB  - Acetaminophen is the most widely used and recommended nonprescription analgesic
      and antipyretic medication in the United States (Rose, 1994). Because
      acetaminophen is widely advertised and readily available over the counter,
      consumers as well as health care professionals perceive this medication to be
      nontoxic. Large or repeated doses of acetaminophen can produce hepatotoxicity,
      which can occur within 24 hours of an overdose. However, because the signs and
      symptoms of acetaminophen overdose mimic common illnesses, the real diagnosis may
      go undetected (Baer & Williams, 1996). Early detection and treatment of
      acetaminophen overdose is imperative to avoid hepatotoxicity. Nurses play a key
      role in early identification of both recommended dosages and the clinical
      features that are associated with acetaminophen toxicity.

PMID- 9239069
TI  - Patellar complications in total knee replacement.
AB  - Over the past 26 years there have been marked changes in total knee arthroplasty
      components. Combinations of metal and polyethylene have been used in a variety of
      ways in the development of the three major components of the knee prosthesis. The
      metal-backed patellar implant that was considered state-of-the-art in the early
      1980s soon came under criticism due to the high rate of failure and subsequent
      revision. A closer look at patellar resurfacing may suggest that some patellar
      compartments do just as well without being resurfaced.

PMID- 9239070
TI  - Placebos and the need for good communication: the case of George Hunter.

PMID- 9239071
TI  - Pigmented villonodular synovitis.
AB  - Pigmented villonodular synovitis, a rare tumor of the synovial lining of a joint,
      is suggested when aspiration of a chronically swollen and painful single joint
      (usually the knee) yields a brownish fluid. The diagnosis is confirmed by biopsy,
      and the preferred treatment is complete excision of all involved synovial tissue.
      The recurrence rate is directly related to the degree of synovial involvement and
      to the thoroughness of the synovectomy performed. Although pigmented villonodular
      synovitis does not become malignant, it can destroy a joint so that an
      arthroplastic procedure may be necessary.

PMID- 9239072
TI  - [The administration of subcutaneous injections by registered nurses and nurses'
      aides--responsibility according to criminal law and liability according to civil
      law].

PMID- 9239073
TI  - [Profession with a future?].

PMID- 9239074
TI  - [Ethics, history and care intertwined? Is there equal coexistence between ethics
      and religion?].

PMID- 9239075
TI  - [Nutrition for adolescents, especially in nursing schools].

PMID- 9239076
TI  - [Do nurse clinicians influence the working climate and the quality of care? 2.
      Results].
AB  - The second part of this report contains the most important knowledge and the
      results gained through the study carried out at the Inselspital Berne,
      Switzerland, concerning the influence a clinical nurse practitioner has on work
      environment and patient satisfaction. Nurses who had the support of a clinical
      nurse practitioners had better guidelines at their disposal and got more
      feedbacks than the others. There were, however, no great differences between the
      units with a clinical nurse practitioner and those without one regarding
      communication, motivation for further education and support in difficult patient
      situations. The motivation for higher education was remarkably high on all units.
      However, the nurses on the units with a clinical nurse practitioner showed more
      interest in psychological and social matters and they had according literature at
      their disposal. The patients were generally satisfied, although there were
      differences regarding trust of the patients in nurses. Patients of units with a
      clinical nurse practitioner addressed nurses more frequently and easily with
      their problems and questions than patients from other units. This case study
      showed that clinical nurse practitioners play an active and important role
      concerning teamwork, particularly by giving feedbacks and helping to create an
      atmosphere of support regarding personal continuing education, using all
      available resources, discussing patient situations, evaluating them and finding
      solutions.

PMID- 9239077
TI  - [The nursing concept as a basis for the practice of care].
AB  - The first part of the essay depicts the results of the literature research on the
      topic and the development of a research method. This second part describes the
      author's findings. They fall into the following categories: "understanding the
      patient's needs", "how nurses see themselves" and "understanding nursing". The
      interviewees express an understanding of nursing which is client-centered. They
      describe conflicts which arise from the discrepancy between their understanding
      and the daily practice of nursing. The author discusses potential sources of
      conflict and possible solutions.

PMID- 9239078
TI  - [Brain death and organ transplantation: ethical dilemmas for nursing?].
AB  - According to the WHO Program, nurses should be active in public health care as
      equal members of a multiprofessional team. This position requires competent
      professional action, which also implies moral competence, especially necessitated
      by the coming paradigmatic changes caused by shifts in the previous and current
      boundaries of the paradigm human being. One reason for this shift are the greater
      medical technical possibilities. The medical definition of brain death as the
      death of a human being per se is one example of the altered boundary and its
      consequences. Must future components of the nursing metaparadigm be changed
      because of this? To what extent is nursing ethically obligated to integrate
      changes in social values into its metaparadigm, ethics and objectives? The
      nursing metaparadigm, Henderson's definition of nursing, the ICN's Basic Code of
      Ethics, and the nursing model according to Roper, Logan & Tierney were used as
      the basis in the analysis of the subject matter and problems. Furthermore,
      philosophical viewpoints of Jonas & Harris will be included to clarify the
      deontological and teleological aspects of standard ethics. Finally, conclusions
      are drawn about the intra- and interprofessional ethical discourse about brain
      death and organ transplantation among nursing professionals.

PMID- 9239079
TI  - [Organ transplantation and brain death. A critical contribution to the definition
      of brain death].
AB  - The following article is based on a lecture held in February 1996 in Bremen on
      the occasion of the 6. International Symposium of Intensive Medicine. Some
      arguments of the discussion about Brain-Death Definition are inquired. The main
      points are not the identification-methods (diagnosis) of brain-death but the
      function of Brain-Death-Definition. On one hand it is possible to demonstrate
      that the points of criticism are not plausible; on the other hand that the
      discussion about Brain-Death-Definition is a substitute that can't give an answer
      to the real ethical problem. The question is: "Which kind of medicine does the
      society want?" The main objective is to get to the matters of facts in the
      current discussion to create the presupposition reasonable orientation.

PMID- 9239080
TI  - [A new documentation system to simplify a patient-centered nursing process in
      ambulatory care and in long-term care in a nursing facility].
AB  - In 1995/96, the new care insurance was introduced in Germany, regulating longterm
      nursing care in the community and in nursing homes. In order to implement the new
      legislative regulations the Federal Ministry of Labour and Social Affairs
      commissioned the AKI Institute to develop adequate patient centered quality
      standards for care planning and documentation. On the results of a multimethod
      survey a new documentation system was developed that enables a new patient
      centred approach, putting the client's habits and his or her view of health
      problems in the centre of nursing action. Traditional formats were altered to
      facilitate the documentation of the nursing process. The results show clearly
      that care is now more orientated towards a patient's autonomy and wishes. On the
      whole, the documentation is clearer and more systematic.

PMID- 9239081
TI  - [Holistic promotion in the process of nursing care in a home nursing situation-
      an empirical case study].
AB  - This article presents results of an empirical test of the conceptual model of
      "holistic promotion in the process of nursing care" (Krohwinkel, 1991, 1992,
      1993a, b, 1994) in a home care situation within an empirical case study. The
      results show that by an integrated assessment of the client's problems/needs and
      the systematic integration of his abilities and those of his primary related
      person, as well as the application of promoting methods of nursing in the nursing
      process, independence and well-being can be reached in "Activities and
      Existential Experiences of Living" (AEDL's). This independence/well-being leads
      also to a relief of the primary related person, his wife, and therefore
      contributes to the security of the home care situation.

PMID- 9239082
TI  - [Michael Gering's (1918-1969) influence on nursing education in the German
      Democratic Republic].
AB  - In 1945, the young physician Michael Gehring returned from captivity to his home
      in East-Germany. He joined the Liberaldemokratische Partei (LDPD), then went over
      to the SED. After having played a decisive role in establishing one of the first
      outpatients' clinics, he was called to the central administration of health in
      East-Berlin. He transformed the traditional nursing education by integrating it
      into the state system of medical technical colleges. Didactical and methodical
      indications were added to the first curriculum for the new nursing course, which
      had been written by Gehring. He also tried to introduce I.P. Pawlow's
      physiological theory into nursing-theory. It is true that he ignored older German
      and American research on the subject. But concerning the history of nursing his
      performance in improving educational organization in East-Germany has to be
      highly valued.

PMID- 9239083
TI  - [Healthy youths for a better future].

PMID- 9239084
TI  - [Adolescents with chronic diseases].

PMID- 9239085
TI  - [Anorexia nervosa in children and adolescents].

PMID- 9239086
TI  - [Sorry ... no time].

PMID- 9239087
TI  - [He who delegates, also has to document].

PMID- 9239088
TI  - [The book search. II].

PMID- 9239089
TI  - [Nursing in 12 hour time].

PMID- 9239090
TI  - [Importance of the Bobath concept in the care of patients with hemiplegia].

PMID- 9239092
TI  - [Cancer chemotherapy. The price to pay].

PMID- 9239091
TI  - [Speaking of quality of life].

PMID- 9239093
TI  - [Cancer facts in 1997. Treatments and perspectives].

PMID- 9239094
TI  - [Outpatient chemotherapy].

PMID- 9239095
TI  - [Cancer and the quality of life. Home care services].

PMID- 9239096
TI  - [Nursing care and quality of life. Is this our priority?].

PMID- 9239097
TI  - [The touch-massage; a technique for comfort].

PMID- 9239098
TI  - [Decubitus ulcers and dressings. Nursing practices].

PMID- 9239099
TI  - [Handwashing and hydro-alcoholic solutions].

PMID- 9239100
TI  - [The essence of care].

PMID- 9239101
TI  - [The statins].

PMID- 9239102
TI  - [Latex allergy. Mechanisms and predictive factors].

PMID- 9239103
TI  - [Latex allergy. Diagnostic methods and therapeutic advances].

PMID- 9239104
TI  - [Latex allergy. Manufacturing of gloves. An example by the industry].

PMID- 9239105
TI  - [Latex allergy. Care of a patient in surgery].

PMID- 9239106
TI  - [Latex allergy. Perioperative incidents and accidents. Analysis of 62 cases in
      obstetric surgery].

PMID- 9239107
TI  - [The "Plan Blanc"].

PMID- 9239108
TI  - [Radiation protection and the hospital staff].

PMID- 9239109
TI  - [Anesthesia in obstetrics].

PMID- 9239110
TI  - [Anesthesia and professional risk].

PMID- 9239111
TI  - [A pediatric service, resuscitation, neuro-respiratory rehabilitation].

PMID- 9239112
TI  - [Coma and its prognoses].

PMID- 9239113
TI  - [Nursing care of the coma awakening . The contribution of song].

PMID- 9239114
TI  - [Music, coma: a staff project].

PMID- 9239115
TI  - [Music and professional practice].

PMID- 9239116
TI  - [Life habits and nurses' observation].

PMID- 9239117
TI  - [Central venous catheters. Watertight dressings].

PMID- 9239118
TI  - [Care of tunnellized central venous catheters in children].

PMID- 9239119
TI  - [A little harmonious uniformity. Psychiatric nursing society and general diploma
      state nurses society: better understanding the foundation of the conflict].

PMID- 9239120
TI  - [Education and professionalization].

PMID- 9239121
TI  - [Diploma for psychiatric nurses. Parts of a difficult dossier].

PMID- 9239122
TI  - [Notes on the situation of psychiatric nurses after the cabinet decision from 30
      December 1996].

PMID- 9239124
TI  - [A new rubric. Futility].

PMID- 9239123
TI  - [Nursing perspectives. From psychiatry to mental health].

PMID- 9239125
TI  - [The therapeutic way or the nurses' dream].

PMID- 9239126
TI  - Nursing--an endangered species?

PMID- 9239127
TI  - Are you a role model for healthy lifestyles?

PMID- 9239129
TI  - Laser light: waves of the future.
AB  - The use of lasers is becoming more prevalent in the health care arena. Lasers can
      perform functions from lightening spider veins to correcting nearsightedness.
      Nurses must become familiar with lasers as 21st century medicine becomes a
      reality.

PMID- 9239130
TI  - The dilemma over the reuse of 'single-use' medical devices. A risk manager's
      perspective.
AB  - Reusing "single-use" devices can provide cost savings, but must be handled with
      caution. A consensus among health care institutions concerning reuse has yet to
      be formed. Determining whether to reuse "single-use" devices requires research of
      the industry.

PMID- 9239132
TI  - A bag full of sugar. Surgeons find that ordinary table sugar is a sweet adjunct
      to conventional treatment of deep wound healing.
AB  - Table sugar used as an adjunct to antibiotics may be effective in treating deep
      wound infections. Filling infected wounds with sugar has been practiced for
      centuries in some countries.

PMID- 9239131
TI  - Helping halt hypothermia. An overview of in-line blood/solution warmers.
AB  - Preventing hypothermia when delivering fluids to a patient is of critical
      importance. Several varieties of fluid warmers are available to help prevent
      hypothermia. Before deciding which model of warmer to use, health care facilities
      must decide when they will use this technology.

PMID- 9239133
TI  - Excellence through empowered employees: the Alaska Surgical Center experience.

PMID- 9239134
TI  - The person behind the mask.
AB  - Surgical employees may not be able to take the time to get to know each other. A
      program developed in a surgical area let employees stand out as individuals.
      Employees may find the workplace more enjoyable by learning about each other.

PMID- 9239135
TI  - Change in health care--inventing our future.

PMID- 9239136
TI  - Managed care and you (Part II): Managed care liability marketing claims.

PMID- 9239138
TI  - Understanding microwave therapy as a treatment option for benign prostatic
      hyperplasia.

PMID- 9239139
TI  - The effectiveness of a professionally led support group for men with prostate
      cancer.
AB  - PURPOSE: This study investigated the effectiveness of support groups in: (a)
      helping patients and significant others voice their concerns about the physical
      and psychosocial implications of their disease in an emotionally supportive
      context, (b) enhancing patients' understanding of their disease and its
      treatments and side effects, and (c) facilitating more active involvement in
      their treatment. A total of 54 men and some family members participated in seven
      separate groups. Patients were invited to participate with a letter describing
      the goals of the support groups or were referred by nurses and doctors. METHOD:
      The participants met for a series of 10 weekly sessions each of 90 minutes
      duration. The meetings were led by a nurse and a psychologist, who together
      provided information on the medical aspects of the disease and its treatment,
      focused on the psychologic reactions to a diagnosis of cancer, and encouraged
      participants to adopt more active, health-promoting coping strategies. RESULTS:
      The participants were surveyed anonymously by questionnaire at the end of the
      tenth session on their views and attitudes about the support groups and their
      overall satisfaction. The results showed that participants in the support group
      felt they had a better understanding of their illness and perceived themselves as
      more involved in their treatment. They expressed that sharing their experiences
      with others gave them reassurance, helped alleviate their anxiety, and provided
      them with a more positive outlook. CONCLUSION: It was concluded that these
      findings furnished evidence of the effectiveness of support groups in
      facilitating perceptions of enhanced coping in men with prostate cancer.

PMID- 9239140
TI  - The role of the business card in nursing practice.

PMID- 9239141
TI  - Bacillus Calmette-Guerin therapy for bladder carcinoma in situ: use in a clinical
      setting.

PMID- 9239142
TI  - Developing careers despite an environment of downsizing: what worked for one
      nurse.
AB  - My patients are achieving a higher level of success, now that I have used these
      steps. My compensation is better than when, like a piano teacher, I was going to
      people's homes to give lessons. And because continence includes related health
      issues, I am doing the health education I have always enjoyed but seldom had time
      to do when working in acute care settings. Although this application dealt with
      urinary incontinence, the steps can be applied to many other health conditions
      and their management. What would you really like to do professionally? Write down
      everything you can think of, and circle the most likely, or use "right brain
      clustering," and you will be surprised what you can come up with. It might even
      be something you can get paid well for doing.

PMID- 9239143
TI  - Genitourinary embryology and congenital defects.

PMID- 9239144
TI  - [Breast cancers with central localization: conservative treatment by tumorectomy
      with ablation of the areolar plaque].
AB  - OBJECTIVES: In breast cancer, retroareolar tumors are observed in 5 to 20% of
      cases; mammectomy is the conventional treatment. Conservative surgery was used in
      this series of 36 patients with retroareolar cancer situated less than 2 cm from
      the areola. PATIENTS AND METHODS: Tumorectomy with resection of the areolar
      plaque was followed by radiotherapy. Six patients had Paget's disease of the
      nipple, 64% were in classes T0 or T1 and 36% in T2. Chemotherapy or radiotherapy
      was given for tumor reduction prior to surgery in 8 patients. Wide tumorectomy
      with resection of the areolar plaque and gland remodeling was performed in all
      patients. Three plastic surgery techniques were used. Mean tumor size was 17.3 mm
      (8 to 33 mm). The areola was invaded in 16 patients (44%) and the derma or
      retroareolar ducts in 26 (72%). RESULTS: The mean distance between the tumor and
      skin surface was 3.8 mm. The section surface was in healthy tissue in 31 patients
      and 2 patients underwent subsequent surgery for mammectomy. All patients had
      either pre-operative (n = 4) or post-operative (n = 32) radio-therapy. Secondary
      reconstruction of the nipple was performed in 14 patients. CONCLUSION: Histology
      findings and esthetic results suggested that this conservative approach can be
      proposed when the tumor is located close to the areola, as confirmed by our
      series and results from other teams using the same technique.

PMID- 9239145
TI  - [Systemic manifestations of primary Gougerot-Sjogren syndrome. Nature and
      incidence apropos of 34 cases].
AB  - OBJECTIVES: Assess the systemic manifestations observed in patients with primary
      Sjorgen's syndrome and the correlation between clinical findings and paraclinical
      data. METHODS: This retrospective study included patients who met the preliminary
      European criteria established in 1993. RESULTS: Among the 34 patients with
      primary Sjogren's syndrome (32 women, 2 men, mean age 54.9 years), systemic
      manifestations were observed as the inaugural sign in 25 (73.5%) and 31 cases
      (91%) during a mean 43-month follow-up. Clinical signs in 23 patients were:
      neuropsychiatric disorders including depressive syndromes (n = 17) and peripheral
      neuropathies (n = 13), joint and muscle disorders (n = 16), Raynaud's phenomenon
      (n = 8), pulmonary disorders (n = 8), digestive disorders (n = 8) including two
      cases of chronic autoimmune hepatitis, skin disease (n = 7), and renal (n = 3)
      and thyroid (n = 8) disorders. Antinuclear antibodies were found in 20 cases and
      anti-SSA antibodies in 5 associated with anti-SSB in 4. Eight patients had
      hematologic disorders. There was a correlation between the number of systemic
      signs (at least 2) and positive Rose-Bengal test (p = 0.045). DISCUSSION:
      Different systemic manifestations were found at percentages comparable with data
      in the literature except for Raynaud's syndrome which was less frequent and
      neurological disorders which were more frequent.

PMID- 9239147
TI  - [Corticotropin deficiency and hyporeninism-hypoaldosteronism].

PMID- 9239146
TI  - [Acquired cytomegalovirus infection in infants. A case successfully treated with
      ganciclovir].
AB  - BACKGROUND: Congenital cytomegalovirus infection is a severe condition. When
      acquired after birth prognosis is less severe although sensorial sequelae and
      risks justify treatment. CASE REPORT: A 2.5 year old infant with hepatitis due to
      cytomegalovirus infection acquired after birth was treated with intravenous
      ganciclovir (7.5 mg/kg b.i.d for 2 weeks then 10 mg/kg three times a week for 2
      months. No side effect or toxicity was observed and the patient recovered without
      sequellae. DISCUSSION: In our experience, in addition to severe and symptomatic
      congenital cytomegalovirus infections, ganciclovir can be used in the treatment
      of less severe symptomatic acquired cytomegalovirus in infants.

PMID- 9239148
TI  - [Vasculitis related to human immunodeficiency virus infection. Therapeutic
      approach in a patient].

PMID- 9239149
TI  - [Post-traumatic arterial hypertension].

PMID- 9239150
TI  - [Convulsions after renal angiography and angioplasty].

PMID- 9239151
TI  - [Molecular anomalies in malignant hemopathies].
AB  - Much of our understanding of the molecular anomalies involved in the process of
      oncogenesis has resulted from research into malignant hematologic diseases,
      facilitated by the accessibility of hematopoietic cells. For example, in lymphoid
      tumors, rearrangement of the genomic DNA can lead to the juxtaposition of proto
      oncogenes and the highly active sequences regulating synthesis of immunoglobulins
      or T-cell receptors. The subsequent malignancy results from an uncontrolled
      overexpression of a normal protein. This type of "quantitative" anomaly occurs in
      follicular lymphomas where B-cells overexpress the normal BCL2 protein which
      inhibits apoptosis, contributing to immortalization of the B done. The same type
      of rearrangement process can approach gene fragments which fusion and lead to
      production of a highly oncogenic chimerical or truncated abnormal protein. Such
      "qualitative" anomalies occur in myeloid hemopathies. Both types of anomalies
      involve genes controlling the cell cycle, cell differentiation or cell death
      (apoptosis), in particular transcription factors (for example, E2A, RARA, MYC)
      and molecules involved in signal transduction (for example RAS, ABL, LCK). A
      molecular anomaly can be detected in approximately 30% of all cases of acute
      leukemia and in up to 75% of the non-Hodgkin lymphomas. Analysis of the junction
      fragments of the different heavy chains of the immunoglobulins produced in these
      cases provides a specific marker for detecting the B or T-cell clone in digestive
      or skin biopsies. For example, detection of a BCR-ABL transcript in a patient
      with primary thrombocythemia or an atypical myeloproliferative syndrome can be
      diagnostic and detection of the donal immunoglobulin or T-cell receptor
      rearrangement can confirm the malignant nature of the lymphoid proliferation.
      Molecular markers also have prognostic value allowing patient stratification and
      more adapted therapy. Molecular anomalies detected in malignant hematologic
      diseases are thus examples of nearly perfect "tumor-specific" markers.

PMID- 9239152
TI  - [Infectious risk in medical offices: a reality to be fought].
AB  - The notion of nosocomial infection is intimately related with that of working or
      sejourning in a health care institution and would thus not concern the
      physician's office. Nevertheless, the risk of infection does exist in this
      setting, both for patients and personnel, and requires adequate preventive
      measures. The practitioner is called upon to care for patients who have community
      acquired or possibly nosocomial infections following hospitalization and must
      therefore know the type of germ involved, its characteristics, particularly
      antibiotic sensitivity, the predominant modes of transmission and preventive
      measures against propagation, latrogenic infections such as abscess formation at
      a point of injection or septic arthritis after infiltration may also occur. Other
      more technical procedures (endoscopy, minor surgery) may also be a cause of
      contamination. The practitioner also produces wastes (needles, vaccine syringes,
      dressings) which must be disposed of in accordance with legal regulations. One
      must avoid contaminating oneself in order not to contaminate others. This
      requires adequate knowledge and application of elementary rules concerning hand
      washing, asepsis, antisepsis, and waste disposal, essential links in the chain of
      infection transmission.

PMID- 9239153
TI  - [Extrahepatic diseases certainly related to hepatitis C virus].

PMID- 9239154
TI  - [Extrahepatic diseases in patients with hepatitis C virus infection. Probable or
      possible associations].

PMID- 9239155
TI  - [Bio-chemoprevention of cancer].
AB  - Bio-chemoprevention of cancer is a new concept for cancer prevention. As the
      prototype, we address the possibility of gene transfer and expression of crtB
      gene, encoding the enzyme which converts geranylgeranyl pyrophosphate to
      phytoene. The effective production of phytoene was shown by high-performance
      liquid chromatography (HPLC) in crtB transfected cells, and their ability to
      withstand lipid peroxidation was demonstrated against an experimentally-induced
      oxidative stress. The endogenous synthesis of phytoene resulted in suppression of
      the malignant transformation process. This study has laid the groundwork for the
      future development of a genetic chemopreventive method for carcinogenesis.

PMID- 9239156
TI  - [Progress in the treatment of adult acute myeloid leukemia].
AB  - Due to advances in chemotherapy, differentiation therapy and bone marrow
      transplantation (BMT), adult acute myeloid leukemia (AML) has become a curable
      disease, and we are making further efforts to heighten the cure rate. The JALSG
      AML 89 study resulted in a 77% complete remission (CR) rate in 326 adults with
      AML, and a 38% 4.5-year disease-free survival (DFS) in CR cases. The JALSG AML92
      study for APL with all-trans retinoic acid resulted in a 89% CR rate in 196 and
      64% 4-year DFS in CR cases.

PMID- 9239157
TI  - [Recent advances on the treatment of acute childhood leukemia].
AB  - Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed
      a series of protocols for treatment of acute childhood leukemia in children. Life
      table analysis of serial CCLSG protocols for acute lymphoblastic leukemia (ALL)
      revealed that the outcome of overall All has gradually improved with a increase
      of the event free survival (EFS) rates; 41.4 +/- 3.6% at 14 years for the 811
      protocol, 51.3 +/- 3.5% at 11 years for the 841 protocol, 56.7 +/- 3.1% at 8 year
      for the 874 protocol, and 78.2 +/- 3.1% at 5 year for the 911 protocol. Treatment
      outcome and prognostic factors were evaluated in 152 children with acute
      myeloblastic leukemia (AML) treated on three consecutive protocols (ANLL-861,
      8912 and 9205) of CCLSG. Forty-two of these 46 patients (91.3%) in the ANLL-9205
      protocol achieved complete remission and 58.8% of these patients projected a 3
      year disease free survival. These results were apparently superior to those
      obtained with the ANLL-861 and 8912 protocols, which used conventional doses of
      multiple drugs followed by a moderate post remission chemotherapy of long
      duration. This favorable response with the ANLL-9205 protocol was mainly to high
      induction rate of patients with the M4 and M5 subtypes, as compared to those in
      the previous two protocols. An older age (> or = 8 years) and high WBC count (>
      or = 10 x 10(9)/l) predicted an increased risk of relapse in multivariate
      analyses; patients with an age > 8 years and WBC counts > or = 10 x 10(9)/l had a
      4.5 times higher risk of relapse than patients without these adverse features.

PMID- 9239158
TI  - [Recent progress in therapy for chronic myelogenous leukemia].
AB  - In chronic myelogenous leukemia (CML), abnormalities develop in hematopoietic
      stem cells, affecting three hematopoietic cell series, including leukocytes,
      erythrocytes, and platelets. The occurrence of the Philadelphia (Ph1) chromosome
      and BCR/ABL fused genes are involved in its pathophysiology. Methods of treating
      CML consist of bone marrow transplantation, and administration of interferon
      (IFN) and other antineoplastic drugs. Bone marrow transplantation is strongly
      recommended when the patient is young (usually aged 45 years or younger) and a
      donor with identical human leukocyte antigens (HLA) is available. When bone
      marrow transplantation is impossible, administration of IFN is the treatment of
      choice. IFN administration may induce disappearance or a decrease in the Ph1
      chromosome. IFN administration has been demonstrated to significantly increase
      the survival rate over conventional chemotherapy (hydroxyurea or busulfan).

PMID- 9239159
TI  - [Recent progress in the management of malignant lymphoma].
AB  - In this article recent lymphoma-related topics were reviewed. REAL
      classification, a new histopathological classification of lymphoid neoplasm, has
      been controversial in terms of clinical usefulness. However, mantle cell lymphoma
      in the classification has been well established as one histopathological entity,
      and considered an intermediate grade lymphoma in prognosis. In gastric MALT
      lymphoma, Helicobacter pylori might provide the antigenic stimulus for its
      growth. The eradication of H. pylori causes regression of MALT lymphoma, and anti
      H. pylori treatment should be given for this type of lymphoma. The international
      prognostic index has made it possible to make a different therapeutic plan
      according to the risk group. The results of new therapies, such as purine
      nucleoside analogs for low grade B cell lymphoma and high dose chemoradiotherapy
      for high grade aggressive lymphoma, were reviewed.

PMID- 9239160
TI  - [Progress in the treatment of multiple myeloma].
AB  - Melphalan and prednisolone (MP) have been the standard therapy for multiple
      myeloma for more than 25 years. Although they produce an objective response in 50
      60% of patients, complete remission (CR) is rare and the median survival period
      is generally 24 to 30 months. Many combination chemotherapeutic agents have been
      used and resulted in approximately 70% objective response, but the median
      duration of survival has not significantly been improved. VAD regimen is
      effective for many patients with myeloma resistant to MP therapy. Furthermore,
      VAD-cyclosporin combination induces responses in approximately 40% of patients
      with VAD-resistant myeloma, with increased expression of the multi-drug resistant
      gene (MDR). Intravenous administration of high dose-melphalan also produces
      responses in approximately 30% of patients with myeloma resistant to VAD.
      Interferon-alpha therapy with an alkylating agent-glucocorticoid regimen, shows a
      higher response rate but similar survival time, compared with those obtained with
      the MP therapy alone. High-dose therapy with transplantation is promising. High
      dose therapy combined with autologous bone marrow transplantation improves the
      response rate, event-free survival (EFS), and overall survival (OS) in patients
      with myeloma, demonstrated in the prospective, randomized trial by Attal et al.
      Total therapy by Barlogie et al. consisted of non-cross-resistant induction
      regimens, followed by a double autotransplantation (AT) procedure. Compared with
      the outcome of patients receiving standard therapy, dose intensification with
      double AT produces not only higher CR rates but also significantly extends EFS
      and OS in previously untreated patients with myeloma. The reduced mortality rate
      associated with transplantation, and development of new chemotherapeutic agents
      will lead to future improvements of the therapy for multiple myeloma.

PMID- 9239161
TI  - [Treatment of acute myelogenous leukemia in patients more than 80 years old].
AB  - We studied fifteen patients older than 80 years of age with acute myelogenous
      leukemia (AML) treated between 1984 and 1996. Among 15 cases of AML including 7
      de novo cases and 8 from myelodysplastic syndrome (MDS) or hypoplastic leukemia,
      14 patients had complications, including cardiovascular disease, diabetes
      mellitus or other malignancies. Although patients with de novo AML showed high
      peripheral WBC counts and higher cellularity of bone marrow than those from MDS
      or hypoplastic leukemia, it was difficult in some cases to distinguish these
      types of AML from hematological findings. Of the 6 AML cases, three had entered
      complete remission (CR) by a standard dose of combination chemotherapy (BHAC
      DMP). One CR patient has had CR for more than 9 years now with good QOL. Among
      the 3 patients treated by low-dose Ara-C, one attained CR but only for a short
      period. Four other patients received BRM, such as G-CSF or Ubenimex, and 2
      patients died without chemotherapy. Since AML at more than 80 years of age is a
      highly heterogenous disease, it would be reasonable to give antileukemic agents
      according to the individual patient's condition.

PMID- 9239162
TI  - [Comparison of effects between single vs five-day injection of granisetron for
      combination chemotherapy with cisplatin and 5-fluorouracil for head and neck
      cancer].
AB  - Recently, granisetron (KYT), one of the 5-HT3 receptor antagonists, has been
      developed and proved to have a strong effect for cisplatin (CDDP)-induced emesis.
      The combination chemotherapy with CDDP and 5-fluorouracil (5-FU), which has great
      efficacy for head and neck cancer, induces nausea and vomiting as side effects.
      We compared the effects of KYT for CDDP plus 5-FU-induced emesis between two
      administration schedules. Forty patients were randomized to two groups. KYT was
      administered either on day 1 for twenty patients (Group A), or for consecutive 5
      days in another twenty patients (Group B). Additional antiemetics were
      administered in thirteen patients in Group A and seven patients in Group B for
      severe nausea and vomiting even after KYT administration. The times of additional
      antiemetics administration were more frequent in Group B. The nausea score was
      statistically lower in Group B and the duration of nausea or vomiting was
      statistically longer in Group A. The frequency of vomiting was the same in the
      two groups on day 1, but it was controlled faster in Group B. Appetite loss was
      lower on day 7 in Group B. It was concluded that vomit and nausea were controlled
      better in Group B after day 4. Additional antiemetics were not effective, and 5
      consecutive administrations of KYT for chemotherapy with CDDP plus 5-FU was
      effective for late emesis.

PMID- 9239163
TI  - [Antitumor effect of S-1 and cisplatin treatment against human gastric cancer
      xenografted in nude mice].
AB  - The enhanced effects due to the combined use of oral administration of S-1 and
      intraperitoneal administration of Cisplatin (CDDP) were examined with gastric
      cancer xenografts (NUGC 4). S-1, a new anticancer drug, was daily administered at
      10 mg/kg (qld x 5 x 3 weeks). 5-FU level in blood was 1 microgram/ml at two hours
      after the treatment. Antitumor activity was not found in mice with only the CDDP
      treatment. But antitumor activity by S-1 and daily low-dose (1 mg/kg) or
      intermittent treatment (5 mg/kg) of CDDP showed better results than daily S-1
      treatment. The daily low-dose CDDP treatment showed similar efficacy to the
      intermittent administration at the same total dose, but the daily low-dose CDDP
      treatment was better in the light of toxicities. These results suggest that
      treatment with S-1 and daily low-dose CDDP was effective for gastric cancer.

PMID- 9239164
TI  - [Preoperative adjuvant chemotherapy with oral anticancer agents for stomach
      cancer].
AB  - We performed preoperative chemotherapy using oral anticancer agents and compared
      the survival rate with that of the untreated group. The statistical significance
      of effects in the oral anticancer agent groups was tested by multivariate
      analysis of the survival rate. The subjects were 488 patients who underwent
      resection of primary stomach cancer in the Chiba Cancer Center between 1981 and
      the end of 1991. Patients who were gross type 0 preoperatively, who died in the
      hospital or who had multiple or double cancer, were excluded. They were divided
      into two oral anticancer agent groups with 158 patients in the Tegafur group, 163
      in the 5-FU group, and 167 patients in the untreated group. In addition to
      preoperative adjuvant chemotherapy, the age, gender, age, localization, gross
      type, depth of invasion, histological lymph node metastasis and the old
      histological stage were analyzed as explanatory variables. In both the Tegafur
      and 5-FU groups significant differences of p = 0.034 and p = 0.024 were obtained.
      Factors which had significant effects on survival rate were age (p < 0.0001),
      histological lymph node metastasis (p < 0.0001), age (p = 0.0001), depth of
      invasion (p = 0.002), and gross type 4 (p = 0.043). Therefore preoperative
      administration of oral anticancer agents appeared to have a significant effect on
      survival rates.

PMID- 9239165
TI  - [Study of preoperative combination therapy with UFT + CDDP in patients with
      gastric and colorectal cancer--concomitant effects based on the thymidylate
      synthase inhibitory rat].
AB  - The subjects were 39 patients with gastric cancer and 44 patients with colorectal
      cancer divided into a group administered 400 mg/day of UFT orally for 2 weeks
      preoperatively (UFT group) and a group administered 400 mg/day of UFT as well as
      40 mg/m2 (i.v.) of cisplatin (CDDP) by drip infusion once concomitantly (UFT +
      CDDP group). The thymidylate synthase (TS) inhibitory rate was measured in
      resected specimens and lymph nodes, and the concomitant effects of UFT and CDDP
      were investigated. RESULTS: 1) The TS inhibitory rate in tumor tissue showed no
      significant difference between the two groups. 2) The TS inhibitory rate of
      metastasized lymph nodes was higher in UFT + CDDP group than in the UFT group in
      gastric cancer patients (p < 0.05). The TS inhibitory rate by lymph node
      metastasis in patients with gastric cancer or colorectal cancer was significantly
      higher in metastasized lymph nodes than in non-metastasized lymph nodes in the
      UFT + CDDP group (p < 0.05 for gastric cancer, p < 0.05 for colorectal cancer).
      These results indicated that concomitant use of UFT and CDDP appeared to be more
      effective against metastasized lymph nodes, especially in cases of gastric
      cancer, than against the primary tumor focus.

PMID- 9239166
TI  - [TUT-7 phase I clinical study. TUT-7 Study Group].
AB  - A phase I study with TUT-7, a new anthracycline antitumor antibiotic, was
      conducted in 35 malignant tumor patients at 11 institutions nationwide. The study
      was initiated with a single dose at 100 mg/body which was equivalent to 2n, then
      the dose as escalated up to 700 mg/body in accordance with the modified
      Fibonacci's scheme. The dose limiting factor (DLF) was considered to be
      leukopenia, and maximum tolerated dose (MTD) was 700 mg/ body. The consecutive
      days dosing study subsequently conducted started with 25 mg/body/day, and the
      dose level was escalated up to 150 mg /body/day. TUT-7 was orally administered
      for seven (7) to fourteen (14) consecutive days in principle. It was considered
      that DLF was leukopenia and MTD was 100 mg/body/day for consecutive days dosing.
      The study indicated that serum drug concentrations reached their plateaus on the
      5th day after initiation of TUT-7 treatment and the accumulation of this compound
      was low. With these findings, a regimen with a dose of 100 mg/body/day orally
      administered for 14 consecutive days was recommended for early phase II studies.

PMID- 9239167
TI  - [Inhibition of 5-fluorouracil-cisplatin-induced stomatitis by oral cryotherapy:
      use of an ice-bar containing fibrinolysin and deoxyribonuclease combine (Elase)].
AB  - Stomatitis caused by a combined chemotherapy with 5-fluorouracil (5-FU) and
      cisplatin (CDDP) is a serious problem in the course of treatment for patients
      with oral carcinoma. In the present study, we proposed a form of cryotherapy
      using an ice-bar containing fibrinolysin and deoxyribonuclease (Elase) to inhibit
      the stomatitis. The therapeutic effect of the ice-bar cryotherapy was evaluated
      in 20 patients with oral squamous cell carcinoma who were undergoing 5-FU-CDDP
      chemotherapy. Nine of the 20 patients were given the ice-bar cryotherapy while
      the remaining patients were not. As a result, although there was no significant
      difference between the incidence of stomatitis in the groups with and without the
      ice-bar cryotherapy, the incidence of severe stomatitis with ulcers and/or eating
      disturbance in the 11 cases without the ice-bar cryotherapy (90%) was
      significantly higher than that in the 9 cases with the cryotherapy (44%) (p <
      0.05). However, no significant difference in the clinical response rate of the 5
      FU-CDDP chemotherapy was observed between the two groups.

PMID- 9239169
TI  - [A case of advanced breast cancer receiving combination therapy with 5'-DFUR and
      MPA with remarkable results].
AB  - A 75-year-old woman was admitted to our hospital with advanced breast cancer
      (T4bN3M0, Stage IIIb). She received chemoendocrine therapy of 5'-DFUR 800 mg/day
      and MPA 800 mg/ day for 2 months. The main tumor and metastatic lymph nodes were
      remarkably reduced and became resectable. Histological examination revealed
      necrotic change of the tumor tissues. This combination therapy proved very useful
      for advanced breast cancer.

PMID- 9239168
TI  - [Clinical evaluation of 2-mg granisetron tablet for nausea and vomiting induced
      by anticancer drugs including cisplatin].
AB  - The antiemetic effects on nausea and vomiting induced by anticancer drugs and
      safety of a 2-mg granisetron tablet were studied in cancer patients, particularly
      in the field of gynecology, who had been treated with anticancer drugs including
      cisplatin (CDDP) at 50 mg/m2 or more. The 1-mg granisetron tablet is already
      commercially available and used widely in clinical practice by oral
      administration of two tablets per dosage. In this investigation, the clinical
      efficacy, safety and usefulness of a 2-mg tablet, which can be taken more easily,
      were studied. The 2-mg granisetron tablet was judged to be "remarkably effective"
      or "effective" for nausea and vomiting in 22 (66.7%) of 33 patients. For safety,
      neither adverse experiences nor abnormal laboratory values were judged to be of
      clinical significance. The 2-mg granisetron tablet was considered "extremely
      useful" or "useful" in 22 (66.7%) of 33 patients. The above results confirmed the
      excellent antiemetic effect on nausea and vomiting induced by anticancer drugs
      including CDDP and the high degree of safety of a 2-mg granisetron tablet.

PMID- 9239170
TI  - [A case of advanced gastric cancer with carcinomatosa peritonitis effectively
      treated by 5-FU and low-dose CDDP therapy].
AB  - A 66-year-old woman was admitted to our clinic for appetite loss and abdominal
      distension in August 1995. Endoscopic study revealed an advanced gastric cancer
      in the upper body of her stomach. Abdominal CT study revealed massive ascites and
      para-aortic lymph nodal involvement. Cytological study of the ascites revealed
      class V. She was diagnosed to be in the terminal stage of gastric cancer with
      carcinomatosa peritonitis. Combination chemotherapy with 5-fluorouracil (5-FU)
      and low-dose cisplatin (CDDP) was given by continuous intravenous injection of 5
      FU 500 mg/day, and intermittent intravenous injection of CDDP 30 mg/week was
      performed for reduction of the ascites and her complaint. Endoscopic study 6
      weeks after starting chemotherapy could not find crater of the gastric cancer but
      only a shallow ulcerative lesion. The biopsy specimen of that lesion was group
      III. No ascites and over 50% reduction of the para-aortic lymph node were found
      by the abdominal CT study. This state persisted over 4 weeks. No myelo
      suppression, renal dysfunction or any severe side effect were observed during
      chemotherapy. Her performance status improved from 3 to 1.

PMID- 9239171
TI  - [A case of far-advanced gastric cancer treated with neoadjuvant combination
      chemotherapy of UFT, low-dose CDDP and leucovorin, followed by subtotal
      gastrectomy with curative intent].
AB  - We herein present a case of a 70-year-old man with the tentative diagnosis of far
      advanced gastric cancer supposed to be beyond surgical intervention. Neoadjuvant
      chemotherapy enabled us to perform subtotal gastrectomy with curative intent. The
      man was admitted to our hospital with the chief complaint of poor appetite.
      Because preoperative examinations revealed a mass adjacent to the portal vein and
      common bile duct, which was suspected to be lymphnode metastasis or gastric
      cancer directly invading those vital structures, 4 weeks of neoadjuvant
      combination chemotherapy (NACC) (CDDP 10 mg/body, day 1 through day 5/week, UFT
      600 mg/body, every day, Leucovorin 15 mg/body, every day) was given with
      resultant curative resection of the tumor one month after completion of NACC.

PMID- 9239172
TI  - [A case of FIGO stage IV A vulvar cancer successfully treated by neoadjuvant
      chemotherapy with continuous intra-arterial infusion (cisplatin, 5
      fluorouracil)].
AB  - The subject was a patient who had squamous cell carcinoma in the pudendum and the
      inguinal region (12.5 x 8.0 cm and 4.5 x 3.0 cm, respectively). A curative
      operation for FIGO IV A stage (T3N3M0) vulvar cancer is thought to be difficult
      to perform and is resistant to BOMP therapy, so continuous arterial infusion
      therapy consisting of cisplatin (CDDP, 10 mg/day, day 2-4, one shot) and 5
      fluorouracil (5-FU, 250 mg/day, day 1-4, continuous) was performed weekly via
      bilateral femoral arteries to the lower end of the branches of bilateral superior
      gluteal arteries. In consequence, the tumor started to clearly shrink from the
      first week. After treatment with total doses of 210 mg of CDDP and 7,000 mg of 5
      FU, the patient underwent complete resection of the tumor without skin grafting,
      and a histological efficacy of Grade 1-b or above was obtained. No adverse
      reactions were found, and the free Pt AUC in the peripheral blood was 0.85
      mg.hr/l per course. Pt concentration in the pudendum 2 hours after CDDP therapy
      was 2.9 micrograms/g. Because of little adverse reaction and high efficacy, this
      method appeared to be a therapeutic method worth considering from the viewpoint
      of the quality of life of patients with the progressive vulvar cancer prevalent
      in elderly persons.

PMID- 9239173
TI  - [Development of a new tubulin-interacting agent, docetaxel (taxotere) in Japan].
AB  - A new semi-synthetic taxoid, docetaxel (taxotere) was recently developed in
      Japan. The phase I study was initiated in 1991, and the MTD was determined as 70
      90 mg/m2, dose-limiting factor as leukopenia, and recommended dose for the phase
      II study as 60 mg/m2, every 3-4 weeks. The early and late phase II studies were
      conducted based on above dose schedule. After the late phase II studies,
      appreciable responses were obtained against advanced recurrent breast (50.4%) and
      inoperable lung (22.4%) cancers, and the results were accepted by MHW of the
      Japanese Government. Docetaxel possesses an unique tubulin-interacting activity
      (promotion of assembly of stable microtubules) and currently combination studies
      with other anticancer drugs or radiotherapy are ongoing.

PMID- 9239174
TI  - [TNM classification of liver cancer].
AB  - The current TNM classification of the liver was published in 1987 by UICC, which
      is the same as the staging system in the general Rules for the Clinical and
      Pathological Study of Primary Liver Cancer by the Liver Cancer Study Group of
      Japan (3rd Ed.) and was proposed by the Japanese TNM Committee. This was
      established based upon the data obtained before 1985. Thus, the current TNM
      classification does not always meet the latest knowledge of advanced hepatic
      oncology. The disease in which lesions are present both in the left and the right
      hepatic lobe is defined as Stage 4. Multiple liver cancers of multicentric
      carcinogenesis which are present in the two hepatic lobe and which are often
      detected recently, are stage 4 by the current TNM classification. But the
      postoperative prognosis of this kind of multiple liver cancer is found to be
      better than that of stage 4 of the advanced type, and equal to stage 3. Some
      proposals of reversed TNM classification of the liver, made with a small number
      of experienced cases have been published. However, not all of them would be
      convincing even with testing of a large number of cases.

PMID- 9239175
TI  - Risk-taking behavior in adolescents: the paradigm.

PMID- 9239176
TI  - An overview of adolescent eating behavior barriers to implementing dietary
      guidelines.
AB  - Adolescents continue to report food and nutrient intake and physical activity
      levels that conflict with the U.S. Dietary Guidelines and the Year 2000
      objectives. Some of the barriers to healthier eating and exercise are related to
      factors within the adolescent's environment, such as access to healthy food
      choices or availability of preventive nutritional guidance as part of routine
      health care. Many barriers, though, fit into the theoretical framework that
      attempts to describe determinants of other risky behaviors of adolescents. These
      include (1) adolescent and peer subgroup norms that devalue healthy eating
      behavior; (2) participation in other risky behaviors; (3) low competency (actual
      and perceived) in sports, food selection, and food preparation; and (4) familial
      and cultural expectations. Implications were discussed for intervention
      approaches and policy recommendations that help confront these barriers.

PMID- 9239177
TI  - Unhealthy eating and other risk-taking behavior: are they related?

PMID- 9239178
TI  - Methodological issues regarding eating behavior of high-risk adolescents.
AB  - Teens exist in multiple environments that offer a variety of foods and a range in
      nutrient intakes. Currently used dietary data-collection methods may not be
      contemporary and encompass the real world of today's youth. If we consider
      respondent capability when we design our dietary assessment methods, then we can
      increase accuracy and reduce errors in our data. Our methodological challenge is
      to improve collection methods and to: Focus on the teen and his or her respective
      environments, Develop environment-specific probes within food records, recalls,
      checklists, and frequencies, Inbed safeguards to assure impartial reporting when
      surrogate respondents-for example, parents or school food service staff-are
      queried, Differentiate between foods "as offered or available at the home or
      school" versus foods as actually selected and eaten, Tease out the influence of
      peers and older siblings on food choices versus selections based on personal
      choice or cost, Employ cooperative education in the classroom so teens will feel
      comfortable with spontaneous interviews by unfamiliar people, Train students in
      dietary recordkeeping procedures by incorporating assessment activities into the
      classroom instruction. In conclusion, the teen lives in multiple environments
      that influence his or her food and nutrient intake. To increase validity,
      reliability, and our confidence in the dietary data about teens, we must
      acknowledge these microenvironments and evolve our methods. The process must be
      evolutionary not revolutionary like the lives of many teens. The result will be
      an increased accuracy in both defining actual nutrient intakes and exploring the
      role foods and nutrients have in the overall health or nutrient deficit teens
      face.

PMID- 9239179
TI  - Community-based nutrition interventions: reaching adolescents from low-income
      communities.

PMID- 9239180
TI  - The adolescent: vulnerable to develop an eating disorder and at high risk for
      long-term sequelae.

PMID- 9239181
TI  - Risk factors for eating disorders.

PMID- 9239182
TI  - The metabolic responses to starvation and refeeding in adolescents with anorexia
      nervosa.
AB  - Adaptive changes in metabolism result in decreased energy requirements in AN. A
      retrospective study of 21 hospitalized female AN patients demonstrated that
      indirect calorimetry (IC) measurement of resting energy expenditure (REE) was
      significantly lower than REE calculated by the Harris-Benedict equation (HBE).
      The HBE was adjusted by multiple-regression analysis to reflect the hypometabolic
      state of AN, and the adjusted equation was prospectively validated in 37
      hospitalized female AN patients. Refeeding requires an understanding of both
      baseline requirements and metabolic changes that occur during nutritional
      rehabilitation. In our present study, we prospectively evaluated changes in
      fasting and postprandial REE in 50 hospitalized female patients meeting DSM-IV
      criteria for AN. Baseline IC measurements of fasting and postprandial REE were
      obtained within three days of admission, and every two weeks thereafter. Mean
      fasting REE increased significantly from 72 (+/-11.7) to 83.2 (+/-12.6) percent
      of predicted (p < 0.001) during the first two weeks of hospitalization. Likewise,
      postprandial REE also increased significantly from 17.5 (+/-18.2) to 27.9 (+/
      15.9) percent above fasting REE during the same time period (p < 0.01).
      Significant increases in both REE and postprandial REE persisted in patients
      requiring longer hospitalizations. Despite the fact that prescribed energy intake
      and triiodothyronine (T3-RIA) levels increased during refeeding, there was no
      significant relationship between postprandial REE and energy intake or T3 levels
      after baseline. We conclude that energy metabolism in AN adapts to semistarvation
      by a reduction in fasting REE. With refeeding there is a reversal of this
      adaptive function, demonstrated by an increase in both fasting and postprandial
      energy expenditure. The increase in postprandial REE is not related to energy
      intake or thyroid function.

PMID- 9239183
TI  - Childhood-onset anorexia nervosa is a serious illness.

PMID- 9239184
TI  - Adolescents with anorexia nervosa: the impact of the disorder on bones and
      brains.

PMID- 9239185
TI  - Chronic undernutrition during adolescence.

PMID- 9239186
TI  - Persistent alterations in behavior and serotonin activity after recovery from
      anorexia and bulimia nervosa.

PMID- 9239187
TI  - Risk factors for atherosclerosis in young subjects: the PDAY Study.
      Pathobiological Determinants of Atherosclerosis in Youth.

PMID- 9239188
TI  - Precursors of cardiovascular risk in young adults from a biracial (black-white)
      population: the Bogalusa Heart Study.
AB  - Pediatric epidemiology programs have established that the major adult
      cardiovascular (C-V) diseases, coronary-artery disease, and essential
      hypertension, begin in childhood. Cardiovascular risk factors change during
      periods of growth and development, and there are distinct ethnic (black-white)
      and male-female differences that relate to adult heart disease. These risk
      factors have been shown to "track" over a 15-year period and are predictive of
      adult levels. Secular trends show increasing adiposity in the general population
      of children; an overall weight gain of 2 kg occurred during the decade from the
      1970s to the 1980s, and approximately 5 kg during the decade from the 1980s to
      the 1990s. In all likelihood, increasing obesity is related to a more sedentary
      lifestyle. Cardiovascular risk factors also tend to cluster, for example, obesity
      correlates with higher blood pressure and with adverse serum lipoprotein changes.
      Further, a central distribution of obesity clusters with multiple risk factors in
      the insulin-resistant syndrome. Importantly, antemortem risk factors relate to
      actual C-V lesions found at autopsy. Lesions of a progressive nature occur in
      coronary vessels, which can ultimately result in clinical coronary heart disease.
      The development of lesions lag in young women at an equivalent age and with
      similar levels of risk factors. In addition, ethnic differences are noted in the
      development of C-V changes related to atherosclerosis and hypertension. The
      demonstration of C-V disease in early life gives credibility to risk-factor
      examination of children and the need for beginning of prevention in early life.

PMID- 9239189
TI  - Multidisciplinary intervention in adolescents with cardiovascular risk factors.

PMID- 9239190
TI  - School-based programs for health-risk reduction.
AB  - Based on implications from the pediatric studies of cardiovascular risk, it has
      become imperative that practical methods be developed to begin prevention of
      heart disease early in life. Schools provide an excellent setting for introducing
      comprehensive health education and promotion as a public health approach to the
      general population. A number of school-based health education programs have been
      developed (Heart Ahead/Heart Smart, CATCH, Gimme 5) for children in kindergarten
      through high school, in which education and environmental changes have been shown
      to be effective in promoting healthful behaviors. The effective implementation of
      health education depends to a large extent on the training and motivation of
      teachers, administrators, and food service staff. Training Institutes can be
      important for increasing personal awareness, disseminating information and
      materials, motivating health education efforts for teachers, food service staff
      and their students, and evaluating the health risk of school personnel.

PMID- 9239191
TI  - Management of childhood obesity in pediatric practice.
AB  - Evaluation of obese children and adolescents in the pediatric office or clinic
      should include baseline assessment of weight for height and body fatness; rule
      out endocrine and genetic causes of obesity; and evaluate other health-risk
      factors, such as those for cardiovascular disease, cancer, diabetes, and
      hypertension. Treatment of obesity is most successful if realistic goals are set;
      a balanced low-fat/high-fiber diet is stressed; a safe rate of weight loss of 1
      to 2 pounds per week is achieved through a moderate reduction of caloric intake
      (approximately 20-25% decrease); increased physical activity is stressed as much
      as diet; parental support is strong; and behavior therapy is provided during the
      course of treatment to help both child and parent achieve the diet, exercise, and
      behavior goals.

PMID- 9239192
TI  - Overview: nutrition for pregnant and childbearing adolescents.

PMID- 9239193
TI  - Nutrition for pregnant and childbearing adolescents: demographics, developmental
      needs, behavior, and outcome.

PMID- 9239194
TI  - Hormone-mediated changes in nutrient metabolism in pregnancy: a physiological
      basis for normal fetal development.

PMID- 9239195
TI  - Reduction of birth weight among infants born to adolescents: maternal-fetal
      growth competition.

PMID- 9239196
TI  - Implications of the Camden Study of adolescent pregnancy: interactions among
      maternal growth, nutritional status, and body composition.
AB  - One of the principal goals of the Camden Study over the past decade has been to
      document the extent to which pregnancy during adolescence is affected by
      continued maternal growth. Findings from the Camden Study relating to the other
      main goal, the effects of maternal growth during pregnancy on the outcome of
      pregnancy (maternal-fetal competition), are reviewed elsewhere. Contrary to
      widely held beliefs, we have found that there is considerable growth in late
      adolescence for girls, and, in particular, continued development of weight (> 1
      kg/year) and increases in subcutaneous fatness at central sites. Thus, when
      pregnancy occurs during this final phase of adolescent growth, the normal growth
      processes may be exacerbated. That is, the adolescent potential for weight gain
      (as fat) may be exploited. Along with others, we have documented that adolescent
      pregnancy is associated with larger gestational weight gains. Using methods
      sufficiently sensitive to detect maternal growth prospectively, we also found
      that the larger-than-average total weight gains among adolescents appear
      attributable primarily to the growing adolescent gravidas and reflect their
      continued accrual of subcutaneous fat and increased risk for weight retention.
      Excessive gestational weight gain, as is more common among growing adolescent
      gravidas, appears to exacerbate the accumulation of fat at central sites. Aside
      from the consequences to the outcome of pregnancy, adolescents who begin their
      childbearing early while still growing themselves, such as those we have followed
      in the Camden Study over the past decade, may be at particularly increased risk
      for overweight and obesity. Further, the excessive deposition of subcutaneous fat
      at central body sites, as we have documented for adolescent pregnancy, will often
      in later life presage the development of cardiovascular disease, noninsulin
      dependent diabetes mellitus (NIDDM), and hypertension. Thus, far from being
      benign, pregnancy during adolescence, particularly when the adolescent is herself
      still growing, may contribute to long-term risk for obesity-related diseases and
      diminish the quality of life.

PMID- 9239197
TI  - Maternal growth and fetal growth: pregnancy course and outcome in the Camden
      Study.

PMID- 9239198
TI  - Infants of adolescent mothers: the Brazilian experience.

PMID- 9239199
TI  - Nutritional support for the pregnant adolescent.

PMID- 9239200
TI  - Triceps skinfold thickness patterns: Caucasian and African-American adolescent
      full-term pregnancies.

PMID- 9239201
TI  - Promoting healthy eating and ensuring adequate weight gain in pregnant
      adolescents: issues and strategies.
AB  - The seven specific strategies discussed for promoting the nutritional health of
      pregnant adolescents can be categorized into three broad areas: (1) improve
      nutrition knowledge and skills of adolescents, as well as health care providers;
      (2) improve programs, including access to prenatal care, and developing effective
      nutrition interventions; and (3) direct research efforts to better understand
      barriers to behavior change and conduct scientifically rigorous program
      evaluations of efficacy of nutrition interventions. Nutritional health should be
      viewed within the context of improving overall health and lifestyles. Simple
      solutions focused solely at the individual level are not effective. We need to
      advocate for and support policy efforts to address the economic, familial, and
      social issues that impact health and adolescent pregnancy.

PMID- 9239202
TI  - Poor fitness is independently associated with elevated lipids in male
      adolescents.

PMID- 9239203
TI  - Menses in underweight Guyanese adolescents.

PMID- 9239204
TI  - Changes in weight during pregnancy and lactation in adolescents. Evaluation of a
      nonnutritional intervention.

PMID- 9239205
TI  - Physical activity and teenage health. A program to improve cardiovascular
      fitness, health behavior, and coronary disease risk factors in multiethnic
      teenagers.

PMID- 9239206
TI  - Racial differences in bulimic behaviors among high school females.

PMID- 9239208
TI  - Teenage pregnancy. BMI and patterns in weight gain and their effect on glucose
      intolerance.

PMID- 9239207
TI  - The effect of metabolic programming on atherosclerosis and obesity risk factors
      in UK adolescents living in poor socioeconomic areas.

PMID- 9239209
TI  - The effects of undernutrition on the physical organization of rat sciatic myelin
      sheaths: an X-ray scattering study.

PMID- 9239210
TI  - Relationship between physical activity and body composition in adolescents.

PMID- 9239211
TI  - Relationship between postprandial lipemia and body composition in obese girls.

PMID- 9239212
TI  - Total proteins, albumin, immunoglobulins, and C3 fraction in the colostrum of
      adolescent mothers of small for gestational age term infants.

PMID- 9239213
TI  - Food intake of pregnant adolescent women.

PMID- 9239214
TI  - Preliminary results of a multidisciplinary follow-up program for obese
      adolescents.

PMID- 9239215
TI  - Family-oriented detection of cardiovascular risk factors in early adolescence.

PMID- 9239216
TI  - Secular trends in cholesterol for suburban high school students in Long Island,
      New York, 1987-1995.

PMID- 9239217
TI  - Structural brain changes and malnutrition in anorexia nervosa.

PMID- 9239218
TI  - 5th European Society for Analytical Cellular Pathology Congress. Oslo, Norway, 25
      29 May 1997. Abstracts.

PMID- 9239220
TI  - Sports specific diagnostics of physical performance energetic aspects. Symposium.
      Munich, Germany, September 13-14, 1996. Abstracts.

PMID- 9239219
TI  - 6th World Congress of Biological Psychiatry. Nice, France, June 22-27, 1997.
      Abstracts.

PMID- 9239221
TI  - 4th World Conference on Melanoma. Sydney, Australia, 10-14 June 1997. Abstracts.

PMID- 9239222
TI  - IV International Workshop of the Society for Natural Immunity. Helsinki, May 28
      31, 1997. Abstracts.

PMID- 9239223
TI  - Advances in gene technology: biomolecular design, form and function. Proceeding
      of the 1997 Miami Nature Biotechnology Winter Symposium. February 1-5, 1997.

PMID- 9239224
TI  - XVI Congress of the International Society on Thrombosis and Haemostasis.
      Florence, Italy, June 6-12, 1997. Abstracts.

PMID- 9239225
TI  - [Quinagolide and macroprolactinomas a progress?].

PMID- 9239226
TI  - [Treatment of macroprolactinomas with quinagolide (Norprolac)].
AB  - Quinagolide is a non-ergot dopaminergic agonist recently available on the French
      market. The endocrine and tumoral efficacy as well as the safety and tolerability
      of quinagolide in the treatment of macroprolactinomas are reviewed. In this
      situation, plasma prolactin levels are normalized in about 60% of patients and in
      about one third of those who are resistant to bromocriptine. A significant
      decrease in pituitary tumor size is demonstrated by radiographic studies in 58 to
      69% of patients. About one third of patients show more than 50% tumor shrinkage.
      The tolerability of quinagolide is satisfactory in most cases and clearly better
      than that of bromocriptine. Thus, quinagolide is a useful tool in the treatment
      of macroprolactinomas.

PMID- 9239227
TI  - [Neuroendocrine tumors].
AB  - The term "neuroendocrine" designates tumors with common morphology and immuno
      histochemistry characteristics whatever their localization or embryological
      origin. Diagnosis of neuroendocrine tumors implies: assay of markers and peptide
      hormones and scintigraphy examination (ostreoscan); family screening; treatment
      according to localization, degree of histological differentiation and extention
      as well as possible secretion of peptide hormones.

PMID- 9239228
TI  - [Histopathology of neuroendocrine tumors].
AB  - Neuroendocrine (NE) tumors are a heterogeneous group of neoplasms arising in
      various organs and sharing the features of the NE cell system. The term
      "neuroendocrine" is used for cells characterized by their secretory products and
      some cytoplasmic proteins rather than by their localization and embryological
      derivation. Some tumor types can show a characteristic pattern on conventional
      histology but, to obtain an accurate diagnosis of many NE tumors it is necessary
      to employ various special methods, mainly electron microscopy and immuno
      histochemistry. The classification of NE tumors in four categories according to
      Travis et al. is largely used: typical carcinoid and atypical carcinoid are low
      grade neoplasms; small cell NE carcinoma and large cell NE carcinoma are high
      grade neoplasms. The size, extension into surrounding tissues, angioinvasion and
      hormonal function are also important to consider in the prognostic evaluation of
      some NE tumors. Tumors exhibiting multidirectional differentiation must be
      classified in carcinoma with interspersed NE cells, carcinoid with interspersed
      non NE cells, composite tumors and amphricine tumors. Finally, some NE tumors may
      present features suggesting a Multiple Endocrine Neoplasia, ie. multifocality and
      association with hyperplasia of endocrine cells.

PMID- 9239229
TI  - [Recent data on molecular genetics of neuroendocrine tumors].
AB  - Genetic studies of neuroendocrine tumors were mainly performed on the basis of
      major syndromes predisposing to endocrine and associated proliferative lesions.
      Carcinoid tumors and tumors of the pancreatic islet cells occur in Multiple
      Endocrine Neoplasia type 1, Neurofibromatosis type I, Von Hippel-Lindau disease,
      Tuberous Sclerosis, suggesting that alterations of the major genes responsible
      for these genetic syndromes are crucial mechanisms in the neuroendocrine
      pathogenesis. Tumoral progression and metastasis result from secondary genetic
      events or deregulation involving specific genes, oncogenes, suppressor genes, and
      growth factors. Mechanisms involving mitosis, cell cycle, and cellular adhesion
      might be relevant in the metastatic process. This report is an overview of
      experimental data on this topic and attempt to understand the major events
      inducing a malignant evolution of the normal neuroendocrine tissue.

PMID- 9239230
TI  - [Eutopic and ectopic production of glycoprotein hormones alpha and beta
      subunits].
AB  - Human chorionic gonadotropin (hCG) is a glycoprotein composed of two subunits,
      alpha and beta, linked together by a covalent bond. Ectopic production of hCG has
      been described in various histological types of cancer. Actually, these malignant
      tumors predominantly secrete the free beta subunit (hCG beta) and not hCG.
      Production of free hCG beta is especially found in patients with bladder,
      pancreas, uterine and lung tumors. In patients with neuroendocrine tumors, serum
      levels of free hCG beta are higher in gastrointestinal-pancreatic and lung
      tumors. The significance of ectopic production of hCG beta--epiphenomena or
      intrinsic biological role--remains unknown. Several reports on the similar
      structure of hCG beta and certain growth factors suggest that free hCG beta could
      have an effect on cell proliferation. Increased serum levels of the free alpha
      subunit are found mainly in patients with neuroendocrine tumors localized in the
      gut or lung. Serum levels may also be raised in patients with a pituitary tumor,
      but such production is often associated with a rise in other pituitary hormones.
      The free alpha subunit plays a role in embryon development and would stimulate
      production of prolactin by decidual cells. The free alpha subunit may also play a
      role in tumor growth.

PMID- 9239231
TI  - [Hormones and adipocyte development].
AB  - Dormant preadipocytes isolated from adipose tissue are able to differentiate into
      adipocytes in vitro. A few adipogenic hormones (glucocorticoids or prostacyclin,
      IGF-I and insulin) are sufficient to trigger the differentiation program. In
      preadipose and adipose cells, glucocorticoids play a cardinal role by regulating
      the expression of numerous genes and by increasing the production of prostacyclin
      which acts as an intracrine/autocrine/paracrine effector. Fatty acids and
      metabolites (including prostacyclin) enhance adipocyte differentiation via the
      activation of nuclear peroxisome proliferator-activated receptors (PPARs). PPARs
      then modulate positively the expression of various lipid-related genes involved
      in triacylglycerol accumulation. These in vitro observations emphasize the
      importance of the hypothalamic-pituitary-adrenal axis and provide also a link
      which may take place in vivo between high-fat diets and the excess of adipose
      tissue development.

PMID- 9239232
TI  - Leptin and other secretory products of adipocytes modulate multiple physiological
      functions.
AB  - The view that the adipocyte acts only as a passive storage site for energy in the
      form of triglyceride has been rendered obsolete by the discovery that adipocytes
      secrete a variety of metabolically active molecules. These molecules include free
      fatty acids, which decrease the rate of glucose oxidation by peripheral tissues;
      adipsin and other complement factors involved in host defense; tumor necrosis
      factor alpha, which may be an important determinant of insulin sensitivity; and
      angiotensinogen, which appears to promote terminal differentiation of preadipose
      to adipose cells. Leptin, a 167 amino acid polypeptide encoded by the obese gene,
      is a recently described adipocyte secretory product that communicates the status
      of the body's energy reserve to the central nervous system, apparently for the
      purpose of regulating body composition. Plasma leptin levels are exponentially
      related to total adipose mass. Daily injection of leptin into ob/ob mice leads to
      decreased food consumption and increased energy expenditure, both of which result
      in loss of adipose mass. Leptin-treated animals also have lower circulating
      insulin and glucose levels than pair fed controls. Finally, leptin corrects the
      infertility of ob/ob mice by restoring gonadotropin secretion to normal. These
      observations indicate that the adipocyte plays a key role in energy balance,
      insulin action, host defense, and reproduction, and suggest new approaches for
      understanding several important human diseases.

PMID- 9239233
TI  - Central nervous system and body weight regulation.
AB  - The discovery of both neuropeptide Y and of leptin has led to a better
      understanding of the pathophysiology of obesity syndromes in animal models. It
      has strengthened the concept of the importance of the hypothalamus in the
      etiology of these syndromes. Due to alterations in the regulation of the
      hypothalamus, e.g. by insulin, by leptin or by decreases in the availability of
      glucose in specific brain areas, most animal models of obesity have higher than
      normal hypothalamic neuropeptide Y levels. As neuropeptide Y is a potent
      orexigenic agent, this hypothalamic defect explains why obese rodents are
      hyperphagic. Increased hypothalamic neuropeptide Y levels produce
      hyperinsulinemia and hypercorticism, two abnormalities previously reported in
      obesity, but whose origin is now known to be driven by neuropeptide Y. As
      hyperinsulinemia favors lipid accretion and muscle insulin resistance, and as
      hypercorticism favors the occurrence of both high circulating triglyceride levels
      and muscle insulin resistance, it may be appreciated that most disorders
      previously reported in obesity can now be explained by high hypothalamic
      neuropeptide Y levels. Leptin, produced and secreted by adipose tissue, is a
      potent anorectic agent whose main action is exerted within the hypothalamus in
      which it has been shown to decrease neuropeptide Y, therefore food intake. Leptin
      secretion is favored, in particular, by insulin as well as by glucocorticoids.
      When leptin is administered to obese mice of the ob/ob strain (which do not
      produce nor secrete leptin due to a gene mutation), their food intake, body
      weight and most metabolic abnormalities are normalized. However, in the majority
      of genetically obese rodents, as well as in obese humans, circulating levels of
      leptin are high. This is related to hyperinsulinemia- and hypercorticosteronemia
      induced leptin oversecretion, as well as to central leptin receptor dysfunctions
      preventing normal leptin access to and action within specific brain areas. Under
      these conditions and to prevent the effects of elevated hypothalamic neuropeptide
      Y levels, neuropeptide Y antagonists or active leptin agonists must be found.
      Neuropeptide Y and leptin further underline the existence of functional
      relationship between the brain (hypothalamus) and the periphery (adipose tissue,
      muscle). Lack of leptin (mutated leptin gene) or inefficient leptin action
      (leptin receptor defect) results in increased hypothalamic neuropeptide Y levels.
      The latter favor hyperinsulinemia and hypercorticism both producing oversecretion
      of leptin which, when inefficient, cannot decrease neuropeptide Y: a vicious
      circle is created which maintains either a "thrifty phenotype" favoring fat depot
      or overt obesity, depending on the degree of hyperphagia.

PMID- 9239234
TI  - [Recent progress in radionuclide imaging of parathyroid glands].
AB  - Scintigraphic imaging of parathyroid glands has been the subject of new
      developments. Efficiency of the technique has been improved by the use of a new
      agent Tc-99m sestamibi (MIBI). A meta-analysis study of the literature confirmed
      the superiority of this agent toward the conventional Tc/T1201. Various protocols
      have been proposed for parathyroid imaging with MIBI they are described with a
      comparison of their advantages and drawbacks. The superiority of a two isotopes
      protocol using Tc-99m sestamibi with Iodine 123 and a subtraction processing
      seems proven. Moreover, this latter protocol allows the use of lateral views
      resulting in a higher accuracy. The visualization of hyperplasic glands is also
      improved by this technique. Comparison of ultrasonography versus Tc-99m sestamibi
      scintigraphy is discussed in the light of recent published materials. The
      scintigraphy appears more sensitive than ultrasonography and specially in the
      detection of mediastinal ectopic glands. Finally the exact role of radionuclid
      imaging of the parathyroids in the management of primary hyperparathyroidism is
      described.

PMID- 9239235
TI  - [Sensitivity and specificity of thyreostimuline (TSH) determination on filter
      paper for the diagnosis of hypothyroidism in the elderly].
AB  - The aim of this study was to measure the prevalence of hypothyroidism in 239
      elderly patients and to determine the validity of TSH assay on blood dried on
      filter paper (spot-test) for the diagnosis of hypothyroidism. The sensitivity and
      specificity of the spot-test were evaluated in a subgroup of 177 subjects. The
      prevalence of hypothyroidism was 14.2% (34/239). The spot-test did not give
      satisfactory results for the diagnosis of hypothyroidism in elderly subjects. Due
      to the lack of specificity, most of the positive results were false positives and
      the clinician had to rely on laboratory determination of plasma TSH level to
      confirm hypothyroidism in half of the patients. We do not recommend the spot-test
      for the diagnosis of hypothyroidism in the elderly. Laboratory assay of plasma
      TSH is required for confirming hypothyroidism in the elderly.

PMID- 9239236
TI  - [Management of precocious puberty in boys. Apropos of a case in a 6-year-old
      boy].

PMID- 9239237
TI  - [Belgian registry of thyroid cancer. Preliminary epidemiological characteristics
      revealed by a retrospective study (1988-1995). Belgian Thyroid Cancer Study
      Group].
AB  - The aim of a cancer registry is to study the incidence of cancer in a well
      determined population and to allow epidemiological research to the setting up of
      diagnosis and therapeutic strategies. The Belgian Thyroid Cancer Study Group
      (BTCSG) was founded in 1990. In the present study we report data collected from
      1988 to 1995 in 397 patients with a differentiated (papillary and follicular)
      thyroid carcinoma living in the french-speaking area of Belgium. The sex ratio
      female/male is 3.5 and the median ages at the diagnosis, is similar (45 yrs, 12
      82) in both sexes. Seven cases of thyroid cancer were registered in young
      patients less than 18 yrs old. Thyroid carcinoma were associated with
      multinodular goiter in more than 50% cases. Cancer was bilateral in 17%.
      Papillary histological type accounts for 84% in our series while its diagnosis
      was established in 45% at early clinical stages (TO-T1). These observations could
      probably be related with 1) broader indications and more aggressive options for
      the surgical removal of diffuse multinodular goiter, 2) more sophisticated
      pathologic examinations that might have led to the detection of a greater
      incidence of occult carcinomas, incidentally discovered. Lymph nodes metastases
      were present at the time of diagnosis in 20%, especially in young patients. The
      risk for local and/or lateral recurrence or distant metastases is significantly
      related to the size of the tumor, histologically verified lymph node metastases
      and the values of the EORTC prognostic index (> or = 50) that additionally takes
      into account the differentiation of the tumor. Considering our short median
      follow-up time of 25 months, it is currently too early to define if the
      controversial attitude about the extent of surgery (total thyroidectomy plus I131
      or individualized surgery) can also negatively influence the risk for recurrence.
      In our series, eight patients died of thyroid cancer.

PMID- 9239239
TI  - [Prognostic factors in differentiated thyroid cancers (medullary excluded)].

PMID- 9239238
TI  - [Anatomo-pathology and histological prognosis of follicular thyroid carcinoma].
AB  - After reviewing the classification and main histopathological features of
      differentiated follicular thyroid carcinoma, characters influencing their
      prognosis are analysed in light of publications from the last ten years. In all
      cases distant metastasis, extrathyroid invasion and age are the most significant
      features; histology, limitation and differentiation are then involved. Lymph node
      metastasis play a role mainly in the evolution of follicular carcinoma. The
      diagnosis of malignancy suspected on fine needle aspiration cytology must be
      confirmed on frozen sections at time of surgery; in the main time extension and
      histological type can be determined and help to choose the appropriate surgical
      procedure. The study of biological parameters such as ploidy, DNA content,
      cellular proliferation or expression of oncogens brings no better information
      than clinicopathological parameters and has presently no practical interest for
      the choice of treatment.

PMID- 9239240
TI  - [First-line surgical treatment of differentiated thyroid cancers].
AB  - Differentiated thyroid cancers represent about 90% of all thyroid cancers. Long
      term prognostic is more often excellent. Surgery is one of the main therapeutic
      procedures with complementary hormone therapy and radio iodine. Lobectomy with
      isthmectomy or total thyroidectomy are two different procedures indicated when
      the disease is limited to the thyroid. The major point of discussion is the
      morbidity after total thyroidectomy in comparison with subtotal thyroidectomy. If
      the disease is extended outside thyroid, total thyroidectomy is the "gold
      standard" associated with lymphadenectomy. It considers central neck compartment
      with possible extension to the lateral compartments to realise the classical
      radical neck dissection. Total thyroidectomy allows secondary administration of
      radio iodine. Prognostic depends more on the cancer himself than the extension of
      the surgical ressection. The main prognostic element is the age of patient with a
      limit of 45 to 50 years between the high and low risk. Morbidity of surgery is
      mainly recurrential palsy and permanent hypoparathyroidism with a rate varying
      between 1 and 5%. Lymphadenectomy increase these risk with a ratio from 1 to 3 in
      most series in the literature.

PMID- 9239241
TI  - [131 iodine for the initial treatment of thyroid cancer].
AB  - Retrospective studies justified the use of 131 iodine after surgery in the
      management of thyroid cancer for reducing recurrences and improving survival.
      Indications based on the evaluation of prognostic factors and on the quality of
      surgical excision are more advisable than systematic administration, particularly
      in small, non aggressive tumors which are diagnosed more and more frequently. A
      high level of endogenous TSH and absence of iodine overload are required.
      Standardized fixed ablative doses reach a high rate of success. Various
      scintigraphic procedures allow precise localization of residual or distant
      uptake. Radioprotection measures must be carefully applied to the patients and
      their environment by a skillful personnel. Side effects are rare after one
      ablation dose but must be systematically noted and treated. Genetic and
      carcinogenetic risks are very low.

PMID- 9239242
TI  - [Principles and modalities of hormonal treatment in therapeutic management of
      differentiated thyroid cancers].
AB  - Since TSH favors thyroid cells growth and proliferation, thyroid hormone
      administration is widely used to reduce TSH secretion in patients treated for
      thyroid cancers. But what degree of TSH suppression is required to inhibit
      tumorgenesis and prevent recurrences remains unknown. High doses of thyroid
      hormone can determine undesirable effects on quality of life, bone mass, or
      cardiac function. These effects have to be evaluated and eventually prevented by
      specific therapies. Probably the degree of TSH suppression has to be adjusted to
      the prognosis of the thyroid cancer and the specific risks for every patient.

PMID- 9239243
TI  - [Treatment of differentiated thyroid cancers of nodular type].
AB  - Papillary and follicular carcinomas are the most frequent thyroid cancers. The
      choice of the treatment is dependent on the prognostic scoring systems. A good
      prognosis is linked to the small size of the nodule (especially) microcarcinoma)
      the age of the patient (less than 40), the lack of extra-thyroid (for papillary
      cancer) or extra capsular (for follicular carcinoma) extension. Total
      thyroidectomy decreases the number of recurrences but does not modify the
      mortality. The risk of laryngeal nerve palsy and hypoparathyroidism is not
      negligible. Lobo-isthmectomy thus can be used in the low risk tumors. Radioactive
      iodine administration is rational after total thyroidectomy but its efficacy is
      questioned. Thyroxine treatment is always prescribed. Taking into account the
      risk of osteopenia and cardiovascular disturbances induced by iatrogenic
      thyrotoxicosis, the desirable serum TSH level is debated.

PMID- 9239244
TI  - [Management of differentiated thyroid cancer of nodular type].
AB  - Mortality and recurrence rate in nodular forms of differentiated thyroid cancer
      are 10 and 15%, raising the question of whether initial treatment was adequate.
      Recurrence and mortality appear to be higher after lobectomy than after total
      thyroidectomy. This could result from the development of dedifferentiated relapse
      or metastasis from residual areas. Metastatic node invasion is frequent (60 to
      80%) but does not lead to a high recurrence rate. Prognosis is poor however due
      to frequent association with visceral metastases. Management should take into
      account the relative degree of malignancy of this cancer and the risk of
      morbidity for long surgical procedures. Lobectomy can be acceptable if no
      criteria of gravity is observed, but total thyroidectomy remains the treatment of
      choice. In patients with criteria of gravity, needle biopsy guides possible node
      dissection. Dissection of the recurrent chain misses 20% of the metastatic nodes,
      while dissection of the supraclavian and middle jugular recurrent chains only
      misses 7.8%. Radioactive iodine and hormone therapy are also indicated in
      patients with signs of gravity.

PMID- 9239245
TI  - [Treatment of differentiated thyroid cancer. Management of invasive cancer].

PMID- 9239246
TI  - [Invasive differentiated thyroid cancers: discussion of therapeutics,
      multidisciplinary approach].
AB  - Although well differentiated treated thyroid cancers have generally an indolent
      course, some of those tumors present with an aggressive pattern, invading
      locoregional structures in the neck (mainly in the central compartment of the
      neck). Patients are usually older than 50 years. Initial treatment should imply
      large resections including the pharynx, a portion of the esophagus and sometimes
      the larynx, reconstruction may be necessary, with the use of flaps (free or
      pedicled). Those major operations have to be balanced with the quality of life
      and the length of expected survival, especially for older people whose adaptation
      to this pattern of survival may be an overwhelming situation (informed consent of
      the patient is necessary, a detailed information about the expected results is
      mandatory). Recent studies at the Mayo Clinic and at the Memorial Sloan Kettering
      Cancer Center have shown that intraluminal invasion of the esophagus or of the
      trachea are indicators of a poor prognosis. Multivariate studies have
      demonstrated that the age of the patient at presentation remains the predominant
      prognostic factor: for patients younger than 45 years, safe margins of excision
      allow a similar survival to that of patients without extrathyroidal extension.
      Whereas, after stratification for age, for older patients, the survival seems not
      to be affected by the size of the tumor or by the uncompleteness of the
      resection, this may be explained, at least partially, by the poor prognosis of
      the disease in those older patients. External beam radiation seems to be useful
      for patients for whom resection with close margins or shave-excision are
      performed. Two recent publications show that external radiation improves the
      survival of patients for whom complete resection of the tumor was not possible.

PMID- 9239247
TI  - [Loco-regional persistence and recurrences of operated differentiated thyroid
      cancers. 22 cases on 589 treated patients from 1964 to 1990, follow-up from 5 to
      31 years].
AB  - AIM OF THE STUDY: Evaluation of frequency and outcome of loco-regional
      persistance and recurrences of differentiated thyroid carcinomas after surgery.
      MATERIAL AND METHODS: from 1964 to December 1990, we operated and followed up
      more than 5 years (from 5 to 31 years): 589 thyroid cancers (309 papillary, 262
      follicullar et 18 Hurthle cells); 145 patients were lost to follow-up (24%), 33%
      of them were microcarcinomas. Surgery consisted ultimately in 411 total
      thyroidectomies, 51 sub-total thyroidectomies, 113 lobectomies with
      isthmusectomies, 9 isthmusectomies or tumorectomies and 4 tracheotomies. Neck
      dissection was not routinely performed but rather selectively (n = 137). All
      Patients were put under suppressive hormone therapy. After total thyroidectomy,
      ablative 131 iodine was almost routinely done. All patients have been controlled
      by clinical examination, radio-iodine scanning and, since 1983, by sequential
      thyroglobulin assays. We have analysed the course of patients according to L. J.
      Degroot's staging (Stage I: Patient with intrathyroidal disease. Stage II:
      Patient with cervical node involvement. Stage III: Patient with extra-thyroidal
      neck invasive disease. Stage IV: Distant metastasis). RESULTS: Stage I, n = 383,
      Stage II, n = 96. Total = 479. Local recurrences in the bed of total
      thyroidectomy were exceptional: n = 2/323 (0.6%). Recurrences in the thyroid
      remnant after non total thyroidectomy were rare: n = 3/156 (2%). Cervical nodal
      recurrences were also rare: n = 7/479 (1.5%). Stage III (n = 73): 34/306
      papillary, 9/78, well differentiated follicular, 25/175 poorly differentiated
      follicular. 2/9 follicular of other type and 3/18 hurtle cell. In 67 patients,
      the loco-regional sterilization was achieved, 5 of which were reoperated for
      nodal cervical metastasis. 6 patients died from continuing loco-regional disease
      and 10 presented distant metastases. 4 of which died from. Among opered patients
      are still alive (52/73 = 71,2%) no loco-regional recurrence persisted.
      CONCLUSION: The true problem is not recurrence but the persistance after surgery
      in stage III patients, despite the application of 1131. The determining factor of
      the persistance and recurrence is the initial stage of the carninomatous disease
      at the time of treatment.

PMID- 9239248
TI  - [Mediastinal metastasis of differentiated thyroid cancers. Treatment by total
      mediastinal curettage in 9 cases].
AB  - Nine patients with mediastinal lymph node metastasis in differentiated thyroid
      carcinoma (7 papillary carcinomas, 1 Hurtle's cells carcinoma, 1 insular
      carcinoma) have been treated by systematic mediastinal dissection, 2 cases arose
      6 and 10 years after the initial surgery, 2 cases after 18 and 20 months, but 5
      revealed their metastases at the moment of the diagnosis or 3 months later.
      Investigations caused by a rise in thyroglobuline level (4 cases) necessarily
      involve a mediastinal CT scan, which always proved conclusive. All the patients
      underwent a median total sternotomy associated with a cervicotomy either for
      total thyroidectomy with conservative bilateral neck dissection, or for revision
      of the initial dissection. We describe the technique of mediastinal dissection
      allowing the resection of all the mediastinal lymph nodes. Mortality was zero and
      morbidity remained reasonable. 3 patients had recurrences: 2 died from multiple
      diffused metastases 18 months later, the third has pulmonary and mediastinal
      metastases well controlled by radio-iodine and external radiotherapy with a 5
      years follow-up 6 are under total remission without sequel with a follow up
      ranging from 6 months to 8 years. Rather uncommon, total mediastinal dissection
      gives a long lasting remission with good living conditions to patients
      unresponsive to other therapies.

PMID- 9239249
TI  - [Role of nuclear medicine in the diagnosis and treatment of macroscopic
      metastases].
AB  - The efficacy of internal radiotherapy of metastases of differentiated thyroid
      carcinoma is optimal when the lesions are small or microscopic in size, but
      decreases rapidly when the metastatic mass exceeds several grams. In this last
      situation the role of internal radiotherapy should be discussed relative to
      surgery (when possible) and external radiotherapy. When metastases do not take up
      iodine-131 (about a third of cases) and are not visualized by conventional
      imaging techniques, several radiopharmaceutical agents with relative tumor
      specificity can facilitate their visualization and guide surgical strategy. None
      of the radiopharmaceutical agents currently under evaluation have demonstrated a
      clear superiority for this purpose.

PMID- 9239250
TI  - [Papillary microcarcinoma].
AB  - The incidence of thyroid papillary microcarcinoma has appeared to increase over
      the last decade, probably because of more extensive use of serial slices for
      pathology. Prognosis is generally good, but the aggressive nature of certain
      tumors justifies an examination of the different risk factors such as age, sex,
      histology type, tumor size, lymph node involvement, and extrathyroid extension in
      order to develop a management scheme. Published results have been rather
      heterogeneous and do not allow a clear conclusion.

PMID- 9239251
TI  - [Treatment of differentiated thyroid cancers in children. Study and follow-up of
      a series of 130 cases at the Gustave-Roussy Institute].

PMID- 9239252
TI  - [Hurthle cell thyroid carcinoma].

PMID- 9239253
TI  - [Thyroid nodule and cancer in pregnant women].
AB  - Most thyroid nodules discovered during pregnancy are benign. In this article, we
      propose a pragmatic attitude for the diagnosis and treatment of such nodules,
      insisting particularly on the importance of thyroid echography and fine needle
      aspiration. For women who have successfully been treated for thyroid cancer
      before pregnancy, we discuss the adaptation of thyroxine substitution when they
      become pregnant, the obstetrical and fetal risks (spontaneous miscarriage, fetal
      abnormalities of the thyroid gland and others), and also potential later risks
      for the child, in relation with previous radioactive iodine administration to the
      mother. Finally, we evoke more difficult questions, such as the rare instances in
      which thyroid cancer is discovered during pregnancy, pregnancy occurring during
      the months immediately following radioiodine treatment, and exceptional cases
      where therapeutic radioiodine was inadvertently given during pregnancy.

PMID- 9239254
TI  - [Differentiated thyroid cancer revealed by cervical adenopathy].

PMID- 9239255
TI  - [Anterior frontal laryngectomy without epiglottoplasty or modified Tucker's
      technique. Proposal for a surgical simplification].
AB  - By replacing epiglottic reconstruction with a muscular translation, we attempted
      to simplify the near total laryngectomy with epiglottic reconstruction and
      improve swallowing disorders. Ten operated patients were followed up for at least
      9 to 22 months. We obtained 9 good results and 1 failure. The long terms results
      have to be evaluated to assess risk of laryngeal stenosis.

PMID- 9239256
TI  - [Use of CO2 laser in endoscopic treatment of Zenker's pharyngo-esophageal
      diverticula. Experience apropos of 33 cases].
AB  - Microendoscopic treatment of hypopharyngeal (Zenker's) diverticulum was performed
      in 31 patients during the period 1990-1995. The CO2 laser combined with the
      operating microscope has been used. 33 endoscopic procedures were performed (2
      procedures were needed for 2 patients). The average age of the patients was 70.3
      years (46-86 years). The average length of the general anesthesia was 48 minutes;
      the average length of the endoscopic procedure was 20 minutes. No major
      complication occurred for 32/33 cases (97%). Mediastinitis occurred for 1 case
      (3%) and was successfully treated by surgical and IV antibiotherapy. The average
      duration of hospitalization was 5 days (3-5 days) (patient with mediastinitis
      excluded): the average follow-up was 19 months (1-62 months). 28/31 patients
      (90.3%) were highly or fairly satisfied. Considering the external approach
      microendoscopic CO2 laser diverticulotomy offers comparable functional results.
      Moreover, this procedure is quick, requires a shorter hospitalization stay and is
      followed by a very low percentage of complications. Additionally, no visible scar
      is noted. Optimal management of Zenker's diverticulum remains controversial.
      However, we advocate that microendoscopic CO2 laser diverticulotomy should be
      considered as a first-line treatment option for patients with hypopharyngeal
      diverticulum.

PMID- 9239257
TI  - [Total unilateral deafness in children. Etiologies and long-term consequences].
AB  - A retrospective study of 72 children with a profound (average hearing loss > 90
      dB) unilateral sensorineural hearing loss (PUSNHL) was carried out in the ENT
      department at the Rouen hospital in 1988 and 1994. This study intended to
      investigate the etiologies, how it was recognized, the age of the onset and the
      results of the medical evaluation of these PUSNHL. We found, in 2 cases, that
      vestibular lesions of the healthy ear were present before the onset of a hearing
      loss on this side, turning the PUSNHL into a bilateral deafness. We tried to
      correlate the etiologies, age of onset of the PUSNHL, status of the opposite ear
      and possible scholar problems in the group of the 42 children followed-up for
      more than 2 years (mean follow-up time = 7 years). Among children suffering from
      PUSNHL, we specified a group with higher risk of school failures, allowing ENT
      physicians to propose more accurate management to these children.

PMID- 9239258
TI  - [Intratemporal surgery of the facial nerve. Apropos of 34 cases].
AB  - The results of facial nerve surgery in the temporal bone have been evaluated in a
      review of 34 cases (19 decompressions and 15 reparations). Decompressions of
      immediate and complete facial paralysis by fracture of the temporal bone that
      have achieved a good motor recovery resulted from early surgery before the 21st
      day (50% of grades I and II, 50% of grades III). After this delay, facial
      recovery did not reach grades I and II any longer. In case of nervous
      interruption of traumatic origin or after tumoral ablation, direct restoration of
      continuity by an intermediary grafting fixed with fibrin glue enabled the
      recovery of a facial function of grade III in 87.5% of the cases. These results
      point out the importance of an early exploration of traumatic facial paralysis
      before the end of the third week, and the interest of using a cable graft fixed
      with fibrin glue to repair directly the facial nerve.

PMID- 9239259
TI  - [Neuroglial heterotopia. Apropos of 8 cases with non-nasofrontal sites].
AB  - Neuroglial heterotopia, glioma, is an uncommon congenital nervous tissue tumor,
      usually found in a nasofrontal localization. About 60 cases with an atypical
      localization, usually in the pterygomaxillary fossa have been reported. We
      present 8 cases. Symptomatology followed CT-scan or MRI identified localization
      and was helpful in orienting diagnosis before biopsy. Exeresis was difficult,
      particularly in deep infratemporal localizations reaching the base of the skull.
      The main risk is recurrence. Different surgical approaches have been discussed
      and should be adapted to each case.

PMID- 9239261
TI  - [The deviated nose. Classification and treatment. Apropos of 100 cases].
AB  - We present a series of 100 deviated noses treated over 5-year period. A
      classification into four groups was proposed and used to determine preoperative
      strategy according to the type of deformation. The main corrective methods were
      lateral cartilage grafts for C-shaped noses and removal and reinstallation of the
      nasal cartilage for S-shaped nose and "lay down" noses. The best results were
      obtained for trauma-induced deformations occurring after puberty. Lay-down nose
      were more difficult to treat than C- and S-shaped noses. Good results can be
      expected in 80% of the cases. Good nasal flow was obtained in 90% of the patients
      and secondary surgery was successful in the other 10%.

PMID- 9239260
TI  - [Inferior turbinectomy in asthmatic children].
AB  - Nineteen children with asthma underwent bilateral inferior turbinectomy from 1990
      to 1995. Mean age was 11.5 years (range 8-17). All had obstructive allergic
      rhinitis and were resistant to long-term local corticosteroids. All operations
      were done under general anesthesia and endoscopic control. Mean hospital stay was
      3 days. The postoperative period was uneventful and mean follow-up is 21 months
      (10-44). The patients described outcome as a clear improvement (n = 15), partial
      improvement (n = 3) and unilateral improvement (n = 1). The effect on asthma was
      more difficult to ascertain due to the number of cofactors. It can be noted
      however that asthma was not aggravated and that in 9 cases episodes decreased in
      frequency. Inferior turbinectomy provides considerable improvement in the comfort
      of patients with asthma, especially in terms of nasal ventilation.

PMID- 9239262
TI  - [Leukoplakia of the vocal cords. Diagnosis and treatment].

PMID- 9239263
TI  - [Cardiac poisoning of cisapride (Prepulsid) must be considered in its
      prescription, specially in premature infants].

PMID- 9239264
TI  - [Long QT syndrome under cisapride in neonates and infants].
AB  - BACKGROUND: Cisapride is frequently used in the newborn and infant for treatment
      of gastroesophageal reflux. Twisting-spikes have been reported in adults due to
      overdosage or therapeutic interaction. We report seven cases of QT prolongation
      in infants treated with cisapride. PATIENTS AND METHODS: Seven children (one full
      term, two mature preterms, four preterm babies), aged (mean, range) 41.8 +/- 21
      days (14-79) weighing 2.1 +/- 1.1 kg (1.2-4), free from any cardiac abnormality,
      except one patent ductus arteriosus, have been studied by ECG and Holter
      monitoring. They received cisapride at a mean dose of 1.31 +/- 0.2 mg/kg/d
      (between 1 and 1.7 mg/kg/d). RESULTS: The corrected QT (QTc: N < 450 ms) was
      increased to 486 ms (450-540) with a notched T-wave pattern. No arrhythmia was
      detected. In five cases, cisapride was stopped and changed to metoclopramide.
      Cisapride dosage was reduced to 0.8 mg/kg/d in the two others. No other
      therapeutic modification was done. A control ECG performed 48 hours after
      therapeutic changes showed a QTc shortening of 74 +/- 18 ms (45-90) and the
      disappearance of the notches independent of any heart rate changes, leading to
      normal QTc values: 413 +/- 21 ms (390-440). CONCLUSION: High cisapride dosage in
      preterm, newborns and infants seems to favor QT prolongation which is reversible
      when dosage is reduced or drug is stopped. The use of cisapride in combination
      with other drugs known to increase QT should be done with extreme caution.

PMID- 9239265
TI  - [Hereditary spherocytosis. Course and value of subtotal splenectomy].
AB  - BACKGROUND: Effectiveness of subtotal splenectomy, a procedure recently advocated
      as an alternative treatment to total splenectomy for patients with hereditary
      spherocytosis (HS), has been evaluated. METHODS AND PATIENTS: Eighty-eight
      patients (74 children) with HS were included in this series. Clinical
      presentations ranged from asymptomatic cases to severe transfusion-dependent
      forms. Stunting of growth occurred in four cases; chronic fatigue was observed in
      30 cases and cholelithiasis in 21 cases. Among the red cell indices measured by
      laser light scattering on Technicon H2, the most reliable for diagnosis was the
      abnormal percentage of hyperdense red cells (98% of HS patients). Osmotic
      gradient ektacytometry, used to measure membrane deformability and impairment of
      maximal deformability due to a reduction of erythrocyte surface, always showed
      the characteristic curves of HS. RESULTS: Subtotal splenectomy was performed in
      24 patients leading to a remnant spleen of about 25% of normal for age volume.
      This decreased the hemolytic rate while adequately sustaining the phagocytic
      function of the spleen (assessed by percentage of "pitted erythrocytes" and
      technetium 99n scans of the remnant). However, the observed reduction in
      hemolytic rate was not as extensive as that observed after total splenectomy (six
      cases) and subtotal splenectomy did not entirely prevent risk of cholethiasis
      (three cases). CONCLUSION: This subtotal splenectomy (+/-cholecystectomy) has to
      be particularly considered for children with transfusion-dependent forms of HS,
      in order to obtain the benefits of increased hemoglobin levels without the
      pending risk throughout life of overwhelming post-splenectomy infections.

PMID- 9239266
TI  - [Cushing disease in children and in adolescents. Therapeutic results].
AB  - BACKGROUND: Trans-sphenoidal surgery is currently the treatment of choice for
      Cushing's disease in children. PATIENTS AND METHODS: The results obtained in 20
      consecutive patients referred to the Pediatric Endocrinology Department of
      hopital Saint-Vincent-de-Paul are reported. RESULTS: A remission of Cushing's
      disease was observed in 12/16 (75%) patients in whom surgery was the first
      treatment. Among these 12 patients, three relapsed (25%) 21 to 80 months after
      surgery. Four patients were initially treated with steroid synthesis inhibitors:
      three of those patients were subsequently operated on and their disease remitted.
      Among the seven patients in whom surgery failed (primary failure or relapse), two
      were reoperated and also remitted. Taken together, 21 operations were performed
      and resulted in four immediate failures (19%), three relapses (14%) and 14 long
      term remissions (67%, follow-up 40 +/- 35 months). None of the biological,
      radiological or operative criteria were predictive of the therapeutic results.
      CONCLUSION: Our results illustrate the efficacy and limits of trans-sphenoidal
      surgery for Cushing's disease of children and emphasize the need for a very long
      follow-up of these patients. Treatment of patients in whom surgery has failed
      (initially or secondarily) is particularly difficult and requires a
      multidisciplinary approach.

PMID- 9239267
TI  - [Severity of ingestion of caustic substance in children].
AB  - BACKGROUND: Caustic ingestion is frequent in children, sometimes leading to
      esophageal stricture. PATIENTS AND METHODS: Between 1988 and 1994, esogastroscopy
      was performed in 65 children after caustic ingestion. The children were
      classified in three groups: no lesion (group A), minimal lesions (group B) and
      severe lesions (group C). Nature of the caustic substance, clinical signs and
      evolution were compared in the three groups. RESULTS: Median age was 2 years for
      the 65 children (24 girls, 41 boys). Ingestion occurred at home (94%) during meal
      periods. Substances were dishwater detergents (n = 14), oven cleaner (n = 10),
      bleach (n = 9), washing powder (n = 4), others (n = 20), more often in a liquid
      form (n = 37) than solid (n = 28). Children had no symptoms (57%), presented
      emesis (n = 20) or abdominal pain (n = 10) not correlated to endoscopic findings,
      and hematemesis (n = 3) or respiratory distress (n = 4), both symptoms seen only
      in group C. Buccal lesions (41%) were not correlated to endoscopic findings.
      After endoscopy, 28 children (43%) were classified into group A and 20 children
      (31%) in group B. Among the 17 children (26%) of the group C, eight developed an
      esophageal stricture: seven long strictures requiring replacement of the
      esophagus, one short stricture requiring repeated dilations. CONCLUSION:
      Esophageal stricture is still a severe complication after caustic ingestion.
      These data stress the interest of controlled studies to confirm the preventive
      role of high dose corticosteroids, and the importance of the prevention of
      accidental caustic ingestions in children.

PMID- 9239268
TI  - [Syncope with long QT interval in a 39 day-old infant treated with cisapride].
AB  - Cardiotoxicity of cisapride may increase when this drug is associated with
      ranitidine. CASE REPORT: A 37-day old term infant, treated with cisapride (1.2
      mg/kg/d) and ranitidine for regurgitations, was hospitalized for malaise. A
      prolonged QT interval (with isolate ventricular extrasystoles), noted at
      admission, disappeared rapidly after cisapride withdrawal. Linkage to cisapride
      was probable, promoted by high dosage and cisapride metabolism inhibition by
      ranitidine, but its plasma concentration was not measured. CONCLUSION: This case
      report stresses the problem of cisapride dosage in infants and the question of an
      interaction between cisapride and ranitidine.

PMID- 9239269
TI  - [Danger of nasal vasoconstrictors in infants. Apropos of a case].
AB  - BACKGROUND: Imidazoline derivatives are alpha-adrenergic agents used in nose
      drops and collyria. Intoxication in children can cause severe central nervous
      system depression and cardiovascular adverse effects, especially in very young
      children. CASE REPORT: A 1-month old girl was admitted after nose-drop
      instillation of naphazoline. At the time of admission, she was comatose, pale,
      hypothermic and presented arterial hypertension, bradycardia and apnea. Arterial
      hypertension was corrected after intravenous infusion with phentolamine mesylate,
      an alpha-antagonist agent. All other symptoms disappeared spontaneously 9 hours
      after the initial instillation. CONCLUSIONS: Imidazoline intoxication due to
      overdose or accidental ingestion is frequent in children. Because nose drops are
      widely available without any medical prescription, nasal vasoconstrictors which
      contain imidazolin derivatives should be discouraged under 7 years of age and
      kept out of children's reach.

PMID- 9239270
TI  - [Neonatal detection of central hypothyroidism].
AB  - BACKGROUND: Congenital hypothyroidism is very rare compared to primary
      hypothyroidism. Its early diagnosis may escape neonatal mass screening using TSH
      assay. CASE REPORT: Anthony was born at 37 weeks, weighing 3,060 g. He presented
      with hypotony, jaundice, tongue protrusion evoking congenital hypothyroidism.
      Thyroid function tests favored hypothyroidism central in origin, while the
      systematic neonatal screening was normal. CONCLUSION: Clinical signs of
      congenital hypothyroidism must lead to more specific tests when neonatal
      screening is normal.

PMID- 9239271
TI  - [Acute respiratory distress due to fat embolism].
AB  - BACKGROUND: Acute respiratory distress occurring in a child without any past
      medical history can have different origins. Pulmonary edema can be lesional or
      hemodynamic in origin. Bronchoalveolar lavage often allows indication of the type
      of lesional oedema. CASE REPORT: A 13-year old child was hospitalized for acute
      respiratory distress 24 hours after knee surgery complicated by a fracture of the
      tibial metaphysis. There were no clinical manifestations of airway obstruction.
      Chest X-ray showed pulmonary parenchymous pathology. Pulmonary edema secondary to
      congestive heart failure was eliminated by doppler echocardiogram. The cause of
      lesional pulmonary edema was found with bronchoalveolar lavage that showed fat
      drops in the cytoplasm of many alveolar macrophages. CONCLUSION: Fat embolism
      syndrome may be confirmed by examination of bronchoalveolar lavage fluid.

PMID- 9239272
TI  - [Severe ketoacidosis because of delayed diagnosis of diabetes in children. 4
      cases to alert physicians].
AB  - BACKGROUND: In France, 48% of children with insulin-dependent diabetes mellitus
      (IDDM) are seen for the first time at the stage of keto-acidosis (DKA), a figure
      far higher than in other countries. The four consecutive cases reported in this
      paper suggest that severity at presentation is directly related to the delay of
      diagnosis. CASE REPORTS: All children, aged 6 to 11, presented with severe
      clinical and metabolic conditions: coma, hemodynamic failure, severe dehydration
      and acidosis (pH = 6.86 to 7.06). However, clinical symptoms were a present from
      2 to 4 months, parents did not worry about them. Family practitioners visited 2
      21 days before admission failed to immediately make the diagnosis of IDDM. True
      DKA was however present in all cases 48 hours prior to admission. CONCLUSIONS:
      Earlier diagnosis of IDDM in children is necessary to reduce morbidity and
      mortality of DKA. General practitioners, pediatricians and emergency care
      practitioners must be made fully aware to consider diabetes in children and to
      use more extensively glucose-tests based on urine and blood strips.

PMID- 9239273
TI  - [Hydroelectrolytic requirements during the first week of life in premature
      infants weighing less than 1000 g. Physiopathology and recommendations].
AB  - Fluid and electrolyte maintenance in very low birth weight infants during the
      first week of life must be adapted to their physiological characteristics and to
      pathological events. Insensible water losses are elevated and may reach 100
      mL/kg/24 h depending upon many factors, such as type of incubator, phototherapy,
      presence of respiratory distress syndrome, changes in transepidermal water losses
      and renal water and electrolyte regulation (prediuretic, diuretic and
      postdiuretic phases); there is also a major risk of hypernatremia and
      hyperkaliema. In cases of insufficient fluid intake the main complication is
      dehydration with hypernatremia. Excessive fluid intake results in increased
      incidence of bronchopulmonary dysplasia, patent ductus arteriosus and necrotizing
      enterocolitis. Hypernatremia is a major risk factor of intracranial hemorrhage. A
      careful management of water and electrolyte requirements is therefore mandatory
      in very low birth weight infants. Guidelines on daily maintenance and management
      are presented.

PMID- 9239274
TI  - [Myelodysplastic syndromes in children, Groupe d'etude des myelodysplasies de
      l'enfant de la Societe d'hematologie et d'immunologie pediatrique (SHIP)].
AB  - Myelodysplastic syndromes (MDS) in children constitute a heterogeneous disorder,
      including 'primary' MDS and MDS associated with constitutional abnormalities. The
      Franco-American-British (FAB) cytological classification for adults can be
      applied for childhood in 50 to 100% of the cases. The transformation into acute
      myeloblastic leukemia often occurs, but stabilisation or spontaneous regression
      of the disease may also be observed. The therapeutic decision is difficult
      because there is no predictive factor of the course of the disease. Allogenic
      bone marrow transplantation is the best curative option when treatment is
      necessary.

PMID- 9239275
TI  - [Sports activities of Swiss youths: practices, motivations and links to health].
AB  - BACKGROUND: Despite the relevance of this research topic from a public health
      perspective, there is currently a lack of objective data on the frequency and
      context of European adolescents' sport activity, their motivations to engage in
      sports, as well as the links between their sport habits and their health
      attitudes and behaviors. OBJECTIVES: 1) to describe the sport habits of
      adolescents in Switzerland and their motivations to get involved in a physical
      activity, 2) to define the sociodemographic profile of adolescents defined as
      athletic, 3) to determine the nature of the associations between the frequency of
      sport activity and health variables. METHOD: In the 1993 Swiss Multicentric
      Adolescent Survey on Health, anonymous self-administered questionnaires were
      distributed to a national representative sample of 10,000 in-school adolescents
      (15 to 20 years old). The answers were investigated by means of univariate
      analyses. RESULTS: Half of the sample do sports more than twice a week, boys more
      often as part of a sports club. Motivations depend on the gender, girls doing
      sports for self image and health motivations and boys for competition and
      relational reasons. Almost all the sociodemographic characteristics show
      statistically significant differences between "non athletic", "fairly athletic"
      and "athletic" adolescents, which suggests the influence of the sociocultural
      background on the perception of sport activity. These three groups also differ as
      regards their health behaviors, attitudes and perceptions; the most athletic
      adolescents generally give more positive answers in terms of prevention and
      perceived health. These findings have implications for health promotion, notably
      as regards the creation of the material conditions more likely to favor
      adolescents' involvement in physical activity.

PMID- 9239276
TI  - [Treatment of acute liver failure in children].
AB  - Among the main causes of acute liver failure (ALF) in children, metabolic
      diseases (especially in infants), viral and toxin or drug induced hepatitis are
      the most frequent. The cause remains, however, undetermined in about 30% of the
      cases. Management must be conducted in a pediatric hepatology unit or intensive
      care unit in relation with a pediatric transplant team in order: 1) to perform
      urgent etiological diagnosis; 2) to initiate specific therapy and symptomatic
      treatment; 3) to evaluate the severity and prognosis of liver disease for
      selection of children for emergency liver transplantation; 4) to evaluate
      contraindications to liver transplantation. The overall survival of post
      emergency liver transplantation for ALF in children averages 65%.

PMID- 9239277
TI  - [Radiological case of the month. Bronchogenic cyst].

PMID- 9239278
TI  - [Varicella and invasive group A streptococcal infections].

PMID- 9239279
TI  - [CHARGE association: new associated anomalies].

PMID- 9239280
TI  - [Congresses: what do we think?].

PMID- 9239281
TI  - [Study of main pathogenic agents of dysenteric syndromes in children].

PMID- 9239282
TI  - [Prenatal pulmonary maturation: survey in maternities of Ile-de-France region].

PMID- 9239283
TI  - [Neonatal meningitis: value of the systematic lumbar puncture].

PMID- 9239284
TI  - [Regulation of gene expression by nutrients].
AB  - Nutrients can regulate, directly or indirectly, the pathway of expression of
      genes coding for enzymes involved in metabolic pathways related to the
      utilization of carbohydrates, lipids and amino acids. On the other hand,
      nutrients such as carbohydrates, lipids or amino acids can generate an specific
      hormonal state in the organism, and hormones are the mediators throughout which
      some genes are activated. The objective of the present review is to show some
      specific examples of dietary and hormonal regulation of enzyme genes involved in
      the metabolism of carbohydrates (phosphoenol pyruvate carboxykinase), lipids
      (malic enzyme) and amino acids (serine dehydratase).

PMID- 9239285
TI  - [Nutritional status of rural school children from Chile's metropolitan region: a
      comparative study: 1989].
AB  - The objective of this study was to carry out a comparative study of the
      nutritional status of a representative sample of 651 rural school children from
      Chile's Metropolitan Region between two periods: 1986-1987 and 1989. The
      percentages of weight/age (%W/A), height/age (%H/A) and weight/height (%W/H), as
      well as Z scores were compared with WHO Tables; head circumference/age (%HC/A),
      with Tanner Tables and brachial anthropometric measurements with Frisuncho
      standards. Socioeconomic status (SES) was measured through Graffar's Modified
      Method. Statistical procedures included analysis of variance, "t" test for
      comparison of the means and chi-square. In 1989, results showed an improvement,
      both present nutritional status (%W/H) and SES as compared with 1986-1987 period.
      %W/A increased and %H/A decreased from 1986-1987 to 1989. %W/H should be a better
      indicator of nutritional status due to the high incidence of growth failure
      (47.4%) which was detected in 51.9% and 30.9% in low-low SES and medium SES,
      respectively (p < 0.001). Obesity was significantly higher in females (23.5%)
      than in males (13.2%) (p < 0.05) by which this problem must be prevented to avoid
      negative consequences in present and adult life. %HC/A positively and
      significantly increased from 1986-1987 to 1989 confirming that educational
      selectivity apparently relates to %HC/A, and not to %W/A or %H/A. Considering
      that only 13.0% of school-age children were beneficiaries of the School Feeding
      Program (PAE), the high prevalence of undernutrition and growth failure in non
      beneficiaries and the fact that most part of the sample (86.9%) belong to low
      SES, it should be necessary to increase the covering of PAE in the rural area of
      Chile's Metropolitan Region.

PMID- 9239286
TI  - [Growth in terms of length of Chilean infants of low socioeconomic status: 1978
      1992].
AB  - In Chile infant malnutrition is better reflected by the length/age indicator than
      by weight/length. In this study we will present the progression of length during
      the first year of life from the year 1978 through 1992 of infants of low
      socioeconomic status. We selected healthy infants with > 3000 g birth weight and
      birth length > 0.5 z. According to type of milk feedings they were defined as CM
      (cow milk) those who were weaned before 4 months of life and EM (exclusive breast
      milk) those who continued exclusive breast milk (as only source of milk solids
      permitted) past 6 months. Infants CM of the 1978-80 cohort had a length at birth
      z +0.21 reaching 1 year with z -0.65, a loss of 0.86 z. Infants from the cohorts
      of 1982-86 and 1988-92 fell from z +0.15 to z -0.37 (a loss of -0.52 z) and +0.16
      to -0.19 (a loss of -0.45 z) between birth and 12 months respectively. EBM
      infants length also fell significantly (delta z: -1.12, -0.69 and 0.59
      respectively). Proteincalorie nutrition was adequate confirmed with weight/age or
      length/weight curves with means of +0.52 throughout the first year. Analysis of
      the length curves by regression shows that the slopes of the 3 cohorts are
      significantly different (< 0.01) for CM and EBM favoring the most recent cohorts.
      Multiple regression analysis identified association of length at 1 year with
      birth weight (p < 0.05), birth length (p < 0.01) and socioeconomic index (p <
      0.01). We suggest that there is an improvement in the trend of Chilean infants
      growth in length for the past 20 years, likely due to improvement in
      socioeconomic level.

PMID- 9239287
TI  - [Powdered milk enriched with iron and ascorbic acid as an intervention measure
      for treating iron deficiency anemia in children seen at a Basic Health Care
      Unit].
AB  - This study was undertaken to verify the influence of the use of iron and Vitamin
      C fortified powdered whole milk on the hemoglobin levels of 238 children, aged 6
      to 18 months, seen at a Basic Health Care Unit in the State of Sao Paulo. The
      powdered milk was fortified with 9 mg of iron (ferrous sulfate) and 65 mg of
      Vitamin C for each 100 g of powder. 4 kg/month were distributed to children under
      one year and 2 kg/month to those over one year of age. Clinical, anthropometric
      and hematological (hemoglobin level measurements) evaluations were performed at
      the onset of the study and at three month intervals after the beginning of the
      supplementation. At the end of the trial, there was still enough milk available
      to extend the intervention for a group of 39 children who had presented the worst
      evolution in the first six months. At the onset of the study, 72.6% of the
      children presented anemia. After 3 and 6 months, these percentages had decreased
      to 38.9% and 18.5%, respectively. Among the children that were followed-up for 9
      months, their were only 2.5% who presented anemia at the end of the intervention.
      The highest prevalences were found in the 6 to 12 months age group and the best
      results in the 10 to 18 month group. There was intrafamilial dilution of the milk
      in 30.7% of the cases. With or without intrafamilial milk sharing, there were
      significant decreases in anemia occurrences with no differences between the two
      groups. The use of fortified milk did not affect the children nutritional
      condition. This study permitted the conclusion that the fortification of
      foodstuffs, besides being the method of election for the prevention of iron
      deficiency, is an excellent alternative for the treatment of and recovery from
      iron deficient anemia in children under two years of age.

PMID- 9239288
TI  - [Iron supplementation in Chilean Mapuche infants of the Cautin Province, Chile].
AB  - A 1.8 ml iron supplementation of ferrous sulfate is administered for 90 days to
      76 Mapuche infants, 12 months of age, male and female, from the rural area of the
      Cautin province of Chile. The iron nutrition is evaluated before and after the
      supplementation, through: hemoglobin, haematocrit, transferrin saturation and
      seric ferritin. Stools test are taken at the infant's home, to confirm the
      supplement intake and to measure the iron excreted. To study the contained of
      dietary Fe a Recordatory 24 hour Inquest (RI) is applied moreover a Proximal
      Chemical Analysis (PCHA) to meal test proceeding from the infant's homes. At 12
      months before starting the supplementation, the anemia prevalence was of 28.3%,
      but it disappear as a result of the intervention. Also 65.3% of the infants
      showed and increase of 1 g or more on their hemoglobin, which indicates that they
      were anemic at the beginning of the iron supplementation. By means of this
      therapeutic test it was find 31% more of anemic infants, indicating more
      sensibility of this method. The high levels of anemia prevalence are due to the
      low iron intake, characteristic of the non lactious foods, which according
      results of the RI reaches an average of 2.8 +/- 1.2 mg of Fe/day, versus 4.8 +/-
      4.0 mg of Fe/day according to PCHA. The observed difference between both test
      showed that there is a process of food environmental contamination, by the use of
      iron utensils and great soil contact. The high environmental contamination could
      also be proved by the high iron excretion stools (140 mg of Fe/100 g of stools).
      This method used to measure the Fe excretion of the supplement, would not be
      valid in rural population groups with similar characteristics to those of the
      studied group, because it does not discriminate between the intake and the
      extremely high environmental contamination. To prevent anemia due to iron absence
      in infants, it is absolutely necessary to have some iron fortified food starting
      at 6 months of age, as a complement for breast milk.

PMID- 9239289
TI  - Nutritional status of institutionalised elderly in Ecuador.
AB  - The nutritional status of 111 elderly men and women aged 60 to 99 years in two
      institutions in the Ecuadorian Andes was evaluated using dietary, anthropometric
      and biochemical measurements. Mean daily energy intakes of men and women were
      1720 and 1650 kcal, respectively (7.2 and 6.9 MJ), corresponding to 1.5 times the
      calculated basal metabolic rate (BMR). 6% of subjects had intakes less than 1.2 x
      BMR and 40% less than 1.5 x BMR. Body mass index (BMI) was below 20 kg/m2 in 21%
      of subjects; 45% were between 20 and 24. Only one subject had a BMI over 29.
      Intakes of protein, calcium, iron, riboflavin and vitamin C were satisfactory, in
      contrast to those of zinc, vitamin A, niacin and thiamin. Using sex- and altitude
      specific cutoffs for hemoglobin, anemia was observed in 11% of subjects.
      Nutritional status, evaluated using biochemical indicators, was satisfactory with
      respect to riboflavin, vitamin A, vitamin E and copper. 14% of subjects had low
      serum zinc levels and 17% had serum albumin values below 35 g/L. Low physical
      activity was associated with low energy intake and low serum albumin levels.

PMID- 9239290
TI  - [Bone mass in celiac patients].
AB  - Bone mineral content was measured in the whole body, the spine (L2-L4) and hip by
      Dual Photonic Absorpciometry (densitometer Norland 2600 Gd-153), in seventeen
      celiac patients, aged 6 to 12 years, with good adherence to the gluten free diet.
      The diagnosed was made before 30 months of age in 50% of cases. Average treatment
      duration was 69.8 +/- 36 months. The randomly selected control group was composed
      of 48 school age children, of the same age and sex of patients. Total bone mass
      (TBM) and bone mineral density (BMD) were expressed as Z scores on the basis of
      normal values established by the authors in Chilean children. Celiac patients had
      lower TBM and BMD of whole body, than controls (-1.11 +/- 0.94 vs 0.00 +/- 0.85
      and -0.59 +/- 0.76 vs 0.06 +/- 0.84, respectively) and at the spine (-0.79 +/-
      1.04 vs 0.003 +/- 0.92 and -1.49 +/- 0.99 vs 0.06 +/- 0.87 respectively). A lower
      TBM was founded at the hip (-0.62 +/- 1.28 vs -0.08 +/- 0.82) without differences
      in BMD. Celiac patients had a lower bone mass than controls despite early
      diagnosis and good compliance with the gluten-free diet. These differences could
      not be atributed entirely to the lower height of celiac patients. These results
      suggest that celiac patients constitute a risk group for development of
      osteoporosis later in life. This fact should be taken into consideration in the
      treatment of this condition.

PMID- 9239291
TI  - [Maternal competence and infant malnutrition: an instrument for its evaluation].
AB  - At the Unit of Nutritional Rehabilitation of La Plata Children's Hospital "Sor
      Maria Ludovica" an inventory was designed to observe in outpatient clinics
      certain behaviors allowing an early detection of disorders in mother-child link.
      We evaluate a sample of 50 mothers with their children between 1 and 24 months
      presenting moderate or severe undernutrition of primary cause, as well as 50
      mothers with their children of the same age, sex, social and economical level of
      the experimental group who never presented undernutrition. This inventory, which
      has the following parts, was applied: 1) verbal maternal behaviour, 2) affective
      maternal behavior, 3) child's hygiene, 4) stimulation of development, 5)
      participation of other persons in child's care, 6) consistency between mother's
      discourse and attitudes. The inventory has been sensitive to the proposed
      objective, showing a highly significant difference when correlate mother-well
      nourished child and mother-undernourished child.

PMID- 9239292
TI  - [Biocultural study of infant malnutrition of primary cause in the urban setting
      of La Plata, Buenos Aires Province, Argentina].
AB  - The present study, of microsocial nature, attempts to recover the biology-culture
      unity in the analysis of child undernutrition. A sample was selected of 52
      children with primary undernutrition and their families, from the population
      attending the Nutritional Rehabilitation Unit of La Plata Children Hospital. The
      specific index was used to measure the low socioeconomic level in families with
      undernourished children. The mothers were interviewed to obtain information on
      the perception and recognition of undernutrition. Observation and interviews to
      the medical staff were performed in ten centers of primary health care (PHC), in
      order to reveal the medical practices related to this problem. The results
      obtained showed that the studied families conjugated the most unfavorable life
      conditions within poverty. Children with adequate weight at birth were
      nutritionally affected between 3 and 18 months of age, leading to height
      disorders. The representations and practices sustained by the mothers, relating
      undernutrition to a popular disease named "pata de cabra" lead to limitations in
      treatment. In PHC centers, conceptual and operative limitations are recorded for
      its detection and early treatment. It is concluded that cultural factors present
      in the two most directly related agents to child health (the mother and the PHC
      center) do not allow to modify the environmental effects that prematurely affect
      the children of poverty.

PMID- 9239293
TI  - [Amaranthus cruentus protein concentrate. Extraction methods. Functional
      properties].
AB  - The most favorable conditions of pH, temperature ratio for the yielding of a
      protein concentrate (PC) of seed flour from Amaranthus cruentus was determined.
      The optimal values were: extraction pH 11, stirring time 1 h 30 min,
      precipitation pH 4.5 and a flour/ solvent ratio of 1:15. Obtained the PC, its
      functional properties were assayed. The PC chemical composition expressed in
      g/100 g was: protein 50.9: humidity 3.3; ethereal extract 5.8; raw fiber 6.4;
      ashes 3.8; total carbohydrates 29.9. The following PC functional properties were
      found: a maximal solubility value of 94.3 at pH 1); emulsification activity (EA)
      47.90 +/- 4.9, water absorption capacity (WAC) 2.0 +/- 0.3; and oil absorption
      capacity (OAC) of 0.7 +/- 0.8. The use of this product as supplement for cereals
      and for others foods with poor lysine content is considered possible. Despite of
      the functional properties which show the hydrophilic character of the protein
      from the Amaranthus cruentus PC, great expectancies are inferred for its future
      utilization in bread products.

PMID- 9239294
TI  - Nutritional evaluation of a high-temperature dried soft wheat pasta supplemented
      with cowpea (Vigna unguiculata (L) Walp).
AB  - The objective of this study was to determine the nutritional quality of the pasta
      described above. The work was unique in the following aspects: 1) the drying
      process was a nonconventional method, consisting of a high-temperature short-time
      (HTST) process; 2) the nutritional quality of the wheat pasta was improved by the
      cowpea supplementation. Cowpea was especially chosen due to it being a staple
      food in the diet of the people in Northeast Brazil. Benefits attributed to the
      HTST drying process include a reduction in bacterial counts, shorter processing
      time and less energy consumption. In addition, there are reports in the
      literature of improved pasta firmness, color intensity, and cooking
      characteristics, when non Triticum durum materials plus drying are used. The
      pasta produced in this work was made using 100% soft wheat flour (SP), and soft
      wheat flour (SF) mixed supplemented with 10, 20 and 30% dehulled cowpea meal
      (CM); referred to as 10, 20 and 30% SP, respectively. The methods utilized in
      this project included: AACC methods for proximate analyses and trypsin inhibitor
      activity determination, atomic absorption spectrophotometry for mineral
      determination, a dye binding procedure for measuring available lysine, HPLC for
      amino acid quantification., FAO/WHO amino acid scoring patterns for chemical
      scores and AOAC for protein digestibility. The protein content of the past as
      supplemented with CM ranged from 11.3 to 14.2%, while the 100% SF pasta (SP)
      contained 10.9%. CM supplementation resulted in 52 to 113% more total lysine, and
      26 to 82% more available lysine in the CM pasta compared to the SP. Chemical
      scores for SP were 45 and 59% for preschool and school-age children,
      respectively. Adding 30% CM to SP improved the above chemical scores to 89 and
      100+, respectively. However, the addition of CM compromised the in vitro protein
      digestibility of SP from 4 to 6%. The addition fo 30% CM provided the SP with
      greater calcium (Ca), iron (Fe), zinc (Zn) and copper (Cu): 44, 49, 91 and 402%
      respectively. Cooking the CM pasta resulted in a 50 to 90% retention of mineral
      content, with the greatest loss being for Cu. In the cooked 30% CM pasta, the
      contents of Fe, Zn and Ca were, respectively, 50, 67 and 243% greater than their
      content in the cooked SP. Of the cooked pasta, the only one displaying trypsin
      inhibitor activity was the 30% CM pasta, which had 0.8 TIU.

PMID- 9239295
TI  - [Physicochemical evaluation of dried salted fish in Venezuela].
AB  - Several physical and chemical characteristics of dried salted fish obtained from
      Venezuelan's market were evaluated. Determinations of moisture, ash, fat,
      protein, pH, sodium chloride. Total Volatile Nitrogen and water activity, were
      performed on such products. Even though on limiting parameters, the values of
      water activity, moisture and NaCl determination, indicated that the fish quality
      was acceptable. Total Volatile Nitrogen and pH values were related more to the
      particular fish species. Four different fish species were salted and dried
      following the "optimal method", and an excellent product was obtained, without
      using expensive or complex methods.

PMID- 9239296
TI  - [Factors affecting the cooking of longissimus muscle beef from Venezuela cattle].
AB  - A survey was conducted to study variation in cookery traits of beef longissimus
      in Venezuela. Cattle originated from the main beef producing regions of the
      country (n = 274) provided steaks to study the effects of cattle type (Zebu
      dairy, Zebu), Sex (bull, steer, heifer), age by dentition (estimated
      chronological age of 2, 3 and 4 yr), maturity levels (A, B,C) and marbling scores
      (none, traces, slight). Cookery traits were affected (P > .05) by marbling and
      maturity. Steaks with "traces" of marbling cooked faster and had more cooking
      losses (P < 0.05) than steaks with marbling amounts described as "slight" or
      "none". Steaks derived from the more mature, "C" cattle, required lesser time
      (i.e., 14 min) and retained 3 g/100 g more weight during cooking than those from
      younger ("A" and "B") maturity groups. Beef from bulls and steers typified as
      Zebu-dairy, lasted more in reaching the cooking endpoint (70 degrees C) than that
      from Zebu counterparts Regardless of age or cattle type, steaks from heifers
      cooked more rapidly than those from bulls and steers. These results call
      attention to some of the important sources of variation of cookery traits of beef
      and afford guidelines for meal planning.

PMID- 9239297
TI  - [Effects of sugar cane molasses on the nutritive value of Canavalia ensiformis
      seeds for broiler chicks].
AB  - Three experiments were conducted to determine the efficacy of sugar cane molasses
      to improve performance of broiler chicks fed a diet containing 30% raw or
      autoclaved Canavalia ensiformis seeds (Jack beans). For this latter purpose,
      canavalia seeds were ground and autoclaved at 120 degrees C and 15 psi during 60
      min. Day-old male chicks (Cobb x Cobb) were used throughout the study. In
      Experiment 1, adding 10% molasses to a control diet devoided of jack beans seeds
      significantly (p < 0.05) increased chick feed intake. However, neither the
      addition of 10% molasses nor of 5% glucose, sucrose, fructose, xylose or corn
      starch to the 30% raw canavalia ration allowed feed intakes similar to that shown
      by the control diet (Experiment 2). Broiler performance was evaluated in
      Experiment 3 in response to diets containing 30% raw or autoclaved jack bean
      meal. Ten-percent molasses was also added to both diets which along with the
      control diet were fed to chiks had free access to diets. Growth was depressed
      when the Jack bean containing diets were pair-fed to chicks. The results
      indicated that the use of molasses does not overcome the deleterious effects on
      chick performance due to the presence of 30% raw or autoclaved jack bean meal in
      the diets.

PMID- 9239298
TI  - [Separation and identification of beta-carotene and its cis isomers by high
      pressure liquid chromatography (HPLC)].
AB  - The separation and identification by HPLC of the cis isomers of beta-carotene was
      studied. A 1.26 mg/ml beta-carotene solution previously isomerized with iodine as
      a catalyst, was eluted with 2% acetone in hexane, from a Ca(OH)2 chromatographic
      column in three bands. The fractions were identified by spectrophotometry and the
      retention times of 2.05, 2.4 and 2.8 min for the 13 cis, all-trans, and 9 cis
      beta-carotene isomers, determined by HPLC, with 1% acetone in hexane as movil
      phase. 22.13 mg % of all-trans beta-carotene were found in a sample of canned
      carrots. It is recommended the analyses of a greater number of samples, the
      determination of the method's sensitivity, reproductibility, and the use of a
      standard of reference of a response factor for calculations.

PMID- 9239299
TI  - Superoxide: a two-edged sword.
AB  - Superoxide (O2-) is the compound obtained when oxygen is reduced by one electron.
      For a molecule with an unpaired electron, O2- is surprisingly inert, its chief
      reaction being a dismutation in which it reacts with itself to form H2O2 and
      oxygen. The involvement of O2- in biological systems was first revealed by the
      discovery in 1969 of superoxide dismutase, an enzyme that catalyzes the
      dismutation of O2-. Since then it has been found that biological systems produce
      a bewildering variety of reactive oxidants, all but a few arising ultimately from
      O2-. These oxidants include O2- itself, H2O2 and alkyl peroxides, hydroxyl
      radical and other reactive oxidizing radicals, oxidized halogens and halamines,
      singlet oxygen, and peroxynitrite. These various oxidants are able to damage
      molecules in their environment, and are therefore very dangerous. They are
      thought to participate in the pathogenesis of a number of common diseases,
      including among others malignancy, by their ability to mutate the genome, and
      atherosclerosis, by their capacity for oxidizing lipoproteins. Their properties
      are put to good use, however, in host defense, where they serve as microbicidal
      and parasiticidal agents, and in biological signalling, where their liberation in
      small quantities results in redox-mediated changes in the functions of enzymes
      and other proteins.

PMID- 9239300
TI  - The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its
      use as an expression vector.
AB  - The yellow fever (YF) virus is the prototype flavivirus. The use of molecular
      techniques has unraveled the basic mechanisms of viral genome structure and
      expression. Recent trends in flavivirus research include the use of infectious
      clone technology with which it is possible to recover virus from cloned cDNA.
      Using this technique, mutations can be introduced at any point of the viral
      genome and their resulting effect on virus phenotype can be assessed. This
      approach has opened new possibilities to study several biological viral features
      with special emphasis on the issue of virulence/attenuation of the YF virus. The
      feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is
      available, as a vector for the expression of heterologous antigens is reviewed.

PMID- 9239301
TI  - Electrophysiological measurements of spectral sensitivities: a review.
AB  - Spectral sensitivities of visual systems are specified as the reciprocals of the
      intensities of light (quantum fluxes) needed at each wavelength to elicit the
      same criterion amplitude of responses. The review primarily considers the methods
      that have been developed for electrophysiological determinations of criterion
      amplitudes of slow-wave responses from single retinal cells. Traditional flash
      methods can require tedious dark adaptations and may yield erroneous spectral
      sensitivity curves which are not seen in such modifications as ramp methods.
      Linear response methods involve interferometry, while constant response methods
      involve manual or automatic adjustments of continuous illumination to keep
      response amplitudes constant during spectral scans. In DC or AC computerized
      constant response methods, feedback to determine intensities at each wavelength
      is derived from the response amplitudes themselves. Although all but traditional
      flash methods have greater or lesser abilities to provide on-line determinations
      of spectral sensitivities, computerized constant response methods are the most
      satisfactory due to flexibility, speed and maintenance of a constant adaptation
      level.

PMID- 9239302
TI  - Effect of urea on biomimetic aggregates.
AB  - The effect of urea on biomimetic aggregates (aqueous and reversed micelles,
      vesicles and monolayers) was investigated to obtain insights into the effect of
      the denaturant on structured macromolecules. Direct evidence obtained from light
      scattering (static and dynamic), monolayer maximum isothermal compression and
      ionic conductivity measurements, together with indirect evidence from
      fluorescence photodissociation, fluorescence suppression, and thermal reactions,
      strongly indicates the direct interaction mechanism of urea with the aggregates.
      Preferential solvation of the surfactant headgroups by urea results in an
      increase in the monomer dissociation degree (when applied), which leads to an
      increase in the area per headgroup and also in the loss of counterion affinities.

PMID- 9239303
TI  - Metabolism of diglycine and triglycine by non-filtering kidneys.
AB  - We have studied the metabolism of diglycine and triglycine in the isolated non
      filtering rat kidney. Kidneys from adult male Wistar Kyoto rats weighing 250-350
      g were perfused with Krebs-Henseleit solution containing either 1 mM diglycine or
      triglycine. The analysis of the peptide residues and their components was
      performed using an amino acid microanalyzer utilizing ion exchange
      chromatography. Diglycine was degraded to a final concentration of 0.09 mM after
      120 min (91%); this degradation occurred predominantly during the first hour,
      with a 56% reduction of the initial concentration. The metabolism of triglycine
      occurred similarly, with a final concentration of 0.18 mM (82%); during the first
      hour there was a 67% reduction of the initial concentration of the tripeptide.
      Both peptides produced glycine in increasing concentrations, but there was a
      slightly lower recovery of glycine, suggesting its utilization by the kidney as
      fuel. The hydrolysis of triglycine also produced diglycine, which was also
      hydrolyzed to glycine. The results of the present study show the existence of
      functional endothelial or contraluminal membrane peptidases which may be
      important during parenteral nutrition.

PMID- 9239304
TI  - Influence of first morning urine volume, fasting blood glucose and glycosylated
      hemoglobin on first morning urinary albumin concentration.
AB  - The aim of the present study was to evaluate the effect of first morning urinary
      volume (collected on three different non-consecutive days), fasting blood glucose
      (determined on the first and third days of urine collection), and glycosylated
      hemoglobin (determined on the first and third days of urine collection) on the
      albumin concentration in first morning urine samples collected on three different
      days. We found 3.6% asymptomatic bacteriuria in the urine samples; therefore,
      every urine sample must be tested to exclude infection. One hundred and fifty
      urine samples were provided by 50 IDDM patients aged 21.9 +/- 7 (12-38) years
      with a disease duration of 6.8 +/- 5.8 (0.4-31) years attending the Diabetes
      Clinic at the State University Hospital of Rio de Janeiro. There were no
      differences in albumin concentration (6.1 vs 5.8 vs 6.2 micrograms/ml; P = NS) or
      urinary volume (222.5 vs 210 vs 200 ml) between the three samples. In addition,
      there were no differences in fasting blood glucose (181.9 +/- 93.6 vs 194.6 +/-
      104.7 mg%; P = NS) or glycosylated hemoglobin (HbA1) (8.4 +/- 1.3 vs 8.8 +/-
      1.5%; P = NS) between the first and third blood samples. Six patients (group 1)
      had a mean urinary albumin concentration of more than 20 micrograms/ml for the
      three urine samples. This group was compared with the 44 patients (group 2) with
      a mean urinary albumin concentration for the three urine samples of less than 20
      micrograms/ml. No difference was found between groups 1 and 2 in relation to
      fasting blood glucose (207.1 +/- 71.7 vs 187.6 +/- 84.6 mg/dl), HbA1 (8.1 +/- 0.9
      vs 8.6 +/- 1.1%) or urinary volume [202 (48.3-435) vs 246 (77.3-683.3) ml].
      Stepwise multiple regression analysis with albumin concentration of first morning
      urine samples as the dependent variable, and urinary volume, fasting blood
      glucose and glycosylated hemoglobin as independent variables, showed that only
      12% (P = 0.01) of the albumin concentration could be accounted for by the
      independent effect of morning urine volume on the first day of urine collection.
      No urine samples showed a change in the cutoff level of 20 micrograms/ml of
      albumin concentration as the result of volume. Fasting blood glucose and
      glycosylated hemoglobin did not influence the urinary albumin concentration.
      Considerable variability in urinary albumin concentration was found in the three
      morning urine samples with a mean intraindividual coefficient variation of 56%.
      In conclusion, in the present study, urinary volume had a minimal, though not
      constant, effect on first morning urinary albumin concentration. Day-to-day
      metabolic and clinical control of IDDM patients, except probably for
      ketoacidosis, should not contraindicate microalbuminuria screening in first
      morning urine samples.

PMID- 9239305
TI  - Standardization of a computerized method for calculating autonomic function test
      responses in healthy subjects and patients with diabetes mellitus.
AB  - The objectives of the present study were 1) to compare results obtained by the
      traditional manual method of measuring heart rate (HR) and heart rate response
      (HRR) to the Valsalva maneuver, standing and deep breathing, with those obtained
      using a computerized data analysis system attached to a standard
      electrocardiograph machine; 2) to standardize the responses of healthy subjects
      to cardiovascular tests, and 3) to evaluate the response to these tests in a
      group of patients with diabetes mellitus (DM). In all subjects (97 healthy and
      143 with DM) we evaluated HRR to deep breathing. HRR to standing, HRR to the
      Valsalva maneuver, and blood pressure response (BPR) to standing up and to a
      sustained handgrip. Since there was a strong positive correlation between the
      results obtained with the computerized method and the traditional method, we
      conclude that the new method can replace the traditional manual method for
      evaluating cardiovascular responses with the advantages of speed and objectivity.
      HRR and BPR of men and women did not differ. A correlation between age and HRR
      was observed for standing (r = -0.48, P < 0.001) and deep breathing (r = -0.41; P
      < 0.002). Abnormal BPR to standing was usually observed only in diabetic patients
      with definite and severe degrees of autonomic neuropathy.

PMID- 9239306
TI  - Effect of bacterial lipopolysaccharide on gastric emptying of liquids in rats.
AB  - The objectives of the present investigation were 1) to study the effect of
      bacterial lipopolysaccharide (LPS) on rat gastric emptying (GE) and 2) to
      investigate a possible involvement of the vagus nerve in the gastric action of
      LPS. Endotoxin from E. coli (strain 055:B5) was administered sc, ip or iv to male
      Wistar rats (220-280 g body weight) at a maximum dose of 50 micrograms/kg animal
      weight. Control animals received an equivalent volume of sterile saline solution.
      At a given time period after LPS administration, GE was evaluated by measuring
      gastric retention 10 min after the orogastric infusion of a test meal (2 ml/100 g
      animal weight), which consisted of 0.9% NaCl plus the marker phenol red (6
      mg/dl). One group of animals was subjected to bilateral subdiaphragmatic vagotomy
      or sham operation 15 days before the test. A significant delay in GE of the test
      meal was observed 5 h after iv administration of the endotoxin at the dose of 50
      micrograms/kg animal weight. The LPS-induced delay of GE was detected as early as
      30 min and up to 8 h after endotoxin administration. The use of different doses
      of LPS ranging from 5 to 50 micrograms/kg animal weight showed that the
      alteration of GE was dose dependent. In addition, vagotomized animals receiving
      LPS displayed a GE that was not significantly different from that of the sham
      control group. However, a participation of the vagus nerve in LPS-induced delay
      in GE could not be clearly demonstrated by these experiments since vagotomy
      itself induced changes in this gastric parameter. The present study provides a
      suitable model for identifying the mechanisms underlying the effects of LPS on
      gastric emptying.

PMID- 9239307
TI  - Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin.
AB  - On the basis of our report that a glycolipoprotein fraction (GLP) extracted from
      Leptospira interrogans contains a potent inhibitor of renal Na,K-ATPase, we
      proposed that GLP-induced inhibition of Na,K-ATPase might be the primary cellular
      defect in the physiopathology of leptospirosis. The present study was designed to
      test this hypothesis by determining whether or not 1). GLP inhibits all the
      isoforms of Na,K-ATPase which are expressed in the tissues affected by
      leptospirosis, 2) Na,K-ATPase from leptospirosis-resistant species, such as the
      rat, is sensitive to GLP, 3) GLP inhibits Na,K-ATPase from intact cells, and 4)
      GLP inhibits ouabain-sensitive H,K-ATPase. The results indicate that in the
      rabbit, a leptospirosis-sensitive species, GLP inhibits with similar efficiency
      (apparent IC50: 120-220 micrograms protein GLP/ml) all isoforms of Na,K-ATPase
      known to be expressed in target tissues for the disease. Na,K-ATPase from rat
      kidney displays a sensitivity to GLP similar to that of the rabbit kidney enzyme
      (apparent IC50: 25-80 and 50-150 micrograms protein GLP/ml for rat and rabbit,
      respectively), indicating that resistance to the disease does not result from the
      resistance of Na,K-ATPase to GLP. GLP also reduces ouabain-sensitive rubidium
      uptake in rat thick ascending limbs (pmol mm-1 min-1 +/- SEM; control: 23.8 +/-
      1.8; GLP, 88 micrograms protein/ml: 8.2 +/- 0.9), demonstrating that it is active
      in intact cells. Finally, GLP had no demonstrable effect on renal H,K-ATPase
      activity, even on the ouabain-sensitive form, indicating that the active
      principle of GLP is more specific for Na,K-ATPase than ouabain itself. Although
      the hypothesis remains to be demonstrated in vivo, the present findings are
      compatible with the putative role of GLP-induced inhibition of Na,K-ATPase as an
      initial mechanism in the physiopathology of leptospirosis.

PMID- 9239308
TI  - Frequency of B cells in normal mice which recognize self proteins.
AB  - The mechanism whereby the immune system avoids self-aggression is one of the
      central issues of Immunology. The discovery of natural autoantibodies, mainly of
      IgM isotype, and of idiotypic interactions between antibodies indicates that
      elements of the immune system interact with self constituents and with
      themselves. Results of studies with soluble antibodies have indicated that the
      pool of circulating IgM represents the end result of a highly selective process
      of B cell activation and differentiation by self proteins resulting in the
      formation of a network. The objective of the present work was to determine the
      frequency of self-reacting B cells in normal mice. We were able to detect B cells
      that recognize self proteins present in extracts of different organs in normal
      adult, 2-3-month old, BALB/c and C57BL/6 mice with an ELISA spot assay. About 1%
      of total IgM-secreting cells among small, LPS-stimulated spleen cells reacted
      with organ extracts, whereas among large spleen cells the frequency was 5- to 10
      fold lower. Immunization induced an increase in the frequency of IgM-secreting
      cells. The present results provide cellular evidence for the results of studies
      done at the serological level. The physiological role of these self-recognizing
      cells, as well as their participation in autoimmune processes, remain to be
      established.

PMID- 9239309
TI  - Long-lasting mnemotropic effect of substance P and its N-terminal fragment (SP1
      7) on avoidance learning.
AB  - We investigated the long-lasting effect of peripheral injection of the
      neuropeptide substance P (SP) and of some N- or C-terminal SP fragments (SPN and
      SPC, respectively) on retention test performance of avoidance learning. Male
      Wistar rats (220 to 280 g) were trained in an inhibitory step-down avoidance task
      and tested 24 h or 21 days later. Immediately after the training trial rats
      received an intraperitoneal injection of SP (50 micrograms/kg), SPN 1-7 (167
      micrograms/kg) or SPC 7-11 (134 micrograms/kg). Control groups were injected with
      vehicle or SP 5 h after the training trial. The immediate post-training
      administration of SP and SPN, but not SPC, facilitated avoidance behavior in rats
      tested 24 h or 21 days later, i.e., the retention test latencies of the SP and
      SPN groups were significantly longer (P < 0.05, Mann-Whitney U-test) during both
      training-test intervals. These observations suggest that the memory-enhancing
      effect of SP is long-lasting and that the amino acid sequence responsible for
      this effect is encoded by its N-terminal part.

PMID- 9239310
TI  - Involvement of the hippocampus, amygdala, entorhinal cortex and posterior
      parietal cortex in memory consolidation.
AB  - A total of 182 young adult male Wistar rats were bilaterally implanted with
      cannulae into the CA1 region of the dorsal hippocampus and into the amygdaloid
      nucleus, the entorhinal cortex, and the posterior parietal cortex. After
      recovery, the animals were trained in a step-down inhibitory avoidance task. At
      various times after training (0, 30, 60 or 90 min) the animals received a 0.5
      microliter microinfusion of vehicle (saline) or 0.5 microgram of muscimol
      dissolved in the vehicle. A retention test was carried out 24 h after training.
      Retention test performance was hindered by muscimol administered into both the
      hippocampus and amygdala at 0 but not at 30 min posttraining. The drug was
      amnestic when given into the entorhinal cortex 30, 60 or 90 min after training,
      or into the parietal cortex 60 or 90 min after training, but not before. These
      findings suggest a sequential entry in operation, during the posttraining period,
      of the hippocampus and amygdala, the entorhinal cortex, and the posterior
      parietal cortex in memory processing.

PMID- 9239311
TI  - Influence of lactation on motor activity and elevated plus maze behavior.
AB  - Lactating rats show less noise-induced freezing and fewer inhibitory responses on
      the 6th day post-delivery when submitted to water and food deprivation in a
      classical conflict paradigm. Lactating mice go more often to the illuminated
      chamber in a light-dark cage and stay longer in it than virgin females. The
      present study was designed to assess the influence of this physiological state,
      i.e. lactation, on the elevated plus maze (EPM) and open-field behavior in adult
      female rats. Total (TL) and central (CL) locomotion and rearing (RF) frequencies
      were measured in an open-field. Number of entries into the open and closed arms
      as well as the time spent in each of these arms were measured in the EPM. percent
      time spent and number of entries into the open arms were calculated and compared.
      In the open-field, TL was significantly decreased (115 +/- 10.6 vs 150 +/- 11.6)
      while CL and RF did not differ from those presented by virgin rats. In the EPM,
      lactating rats displayed a significant reduction in percent time spent (10.9 +/-
      1.5 vs 17.4 +/- 2.3) in the open arms as well as a tendency to a reduction in
      percent entries into the open arms (35.7 +/- 4.7 vs 45.7 +/- 4.3). These results
      show that the physiological state of lactation modulates the open-field and EPM
      behaviors in rats.

PMID- 9239312
TI  - Effect of gamma irradiation on the behavioral properties of crotoxin.
AB  - Crotoxin has been detoxified with gamma radiation in order to improve crotalic
      antiserum production. Nevertheless, present knowledge of the biological
      characteristics of irradiated crotoxin is insufficient to propose it as an
      immunizing agent. Crotoxin is known to increase the emotional state of rats and
      to decrease their exploratory behavior (Moreira EG, Nascimento N, Rosa GJM,
      Rogero JR and Vassilieff VS (1996) Brazilian Journal of Medical and Biological
      Research, 29: 629-632). Therefore, we decided 1) to evaluate the effects of
      crotoxin in the social interaction test, which has been widely used for the
      evaluation of anxiogenic drugs, and 2) to determine if irradiated crotoxin
      induces behavioral alterations similar to those of crotoxin in the social
      interaction, open-field and hole-board tests. Male Wistar rats (180-220 g) were
      used. Crotoxin (100, 250, and 500 micrograms/kg) was injected intraperitoneally 2
      h before the social interaction test. Similarly, irradiated crotoxin (2000 Gy
      gamma radiation from a 60Co source) was administered at the doses of 100, 250,
      and 500 micrograms/kg for the hole-board test, and at the doses of 1000 and 2500
      micrograms/kg for the open-field and social interaction tests. ANOVA complemented
      with the Dunnett test was used for statistical analysis (P < 0.05). Crotoxin
      decreased the social interaction time(s) at the doses of 100, 250 and 500
      micrograms/kg (means +/- SEM) from 51.6 +/- 4.4 to 32.6 +/- 3.7, 28.0 +/- 3.6 and
      31.6 +/- 4.4, respectively. Irradiated crotoxin did not induce behavioral
      alterations. These results indicate that 1) crotoxin may be an anxiogenic
      compound, and 2) in contrast to crotoxin, irradiated crotoxin was unable to
      induce behavioral alterations, which makes it a promising compound for the
      production of crotalic antiserum.

PMID- 9239313
TI  - Hyperalgesic effect induced by barbiturates, midazolam and ethanol:
      pharmacological evidence for GABA-A receptor involvement.
AB  - The involvement of GABA-A receptors in the control of nociception was studied
      using the tail-flick test in rats. Non-hypnotic doses of the barbiturates
      phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30
      mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg)
      administered by the systemic route reduced the latency for the tail-flick
      response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non
      convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg)
      administered systemically induced an increase in the latency for the tail-flick
      response, therefore characterizing an 'antinociceptive' state. Previous
      picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by
      effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital,
      midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A
      specific agonists (muscimol, THIP), which is specifically antagonized by the GABA
      A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically
      involved in the modulation of nociception in the rat central nervous system.

PMID- 9239315
TI  - Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus.
AB  - Short-term experimental diabetes mellitus (DM) produces a significant decrease in
      serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone
      (TSH) and a reduction in hepatic and renal T4-5'-deiodination. However, little is
      known about the effects of chronic diabetes mellitus on the pituitary-thyroid
      axis function. We evaluated the changes induced by very short-term (6 days),
      short-term (15 days) and chronic (6 months) streptozotocin-induced diabetes
      mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'
      deiodinase activity in the thyroid and pituitary glands. Serum hormones were
      determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities
      were assayed in the thyroid and pituitary microsomal fractions using 2 microM T4
      as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0
      micrograms/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5
      micrograms/dl after 15 days of DM, with no significant changes in serum TSH,
      indicating a decreased pituitary TSH responsiveness to the diminished suppression
      by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4
      5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was
      significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six
      months after diabetes mellitus induction, both serum T4 and thyroid T4-5'
      deiodinase returned to normal ranges and serum TSH was unchanged, although
      pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol
      T3/mg protein. These findings indicate that some kind of adaptation to chronic
      insulinopenia may occur at the thyroid level, but this does not seem to be true
      for the pituitary.

PMID- 9239314
TI  - The effects of cyclopiazonic acid on intracellular Ca2+ in aortic smooth muscle
      cells from DOCA-hypertensive rats.
AB  - We tested the hypothesis that cyclopiazonic acid (CPA), an inhibitor of the
      sarcoplasmic reticulum (SR) Ca(2+)-ATPase, increases intracellular Ca2+
      concentration ([Ca2+]) in aortic myocytes and that the increase in [Ca2+]i is
      higher in aortic cells from deoxycorticosterone acetate (DOCA)-hypertensive rats.
      Male Sprague-Dawley rats, 250-300 g, underwent uninephrectomy, received a
      silastic implant containing DOCA (200 mg/kg) and had free access to water
      supplemented with 1.0% NaCl and 0.2% KCl. Control rats were also
      uninephrectomized, received normal tap water, but no implant. Intracellular Ca2+
      measurements were performed in aortic myocytes isolated from normotensive
      (Systolic blood pressure = 120 +/- 3 mmHg; body weight = 478 +/- 7 g, N = 7) and
      DOCA-hypertensive rats (195 +/- 10 mmHg; 358 +/- 16 g, N = 7). The effects of CPA
      on resting [Ca2+]i and on caffeine-induced increase in [Ca2+]i after [Ca2+]i
      depletion and reloading were compared in aortic cells from DOCA and normotensive
      rats. The phasic increase in [Ca2+]i induced by 20 mM caffeine in Ca(2+)-free
      buffer was significantly higher in DOCA aortic cells (329 +/- 36 nM, N = 5)
      compared to that in normotensive cells (249 +/- 16 nM, N = 7, P < 0.05). CPA (3
      microM) inhibited caffeine-induced increases in [Ca2+]i in both groups. When the
      cells were placed in normal buffer (1.6 mM Ca2+, loading period), after treatment
      with Ca(2+)-free buffer (depletion period), an increase in [Ca2+]i was observed
      in DOCA aortic cells (45 +/- 11 nM, N = 5) while no changes were observed in
      normotensive cells. CPA (3 microM) potentiated the increase in [Ca2+]i (122 +/-
      30 nM, N = 5) observed in DOCA cells during the loading period while only a
      modest increase in [Ca2+]i (23 +/- 10 nM, N = 5) was observed in normotensive
      cells. CPA-induced increase in [Ca2+]i did not occur in the absence of
      extracellular Ca2+ or in the presence of nifedipine. These data show that CPA
      induces Ca2+ influx in aorta from both normotensive and DOCA-hypertensive rats.
      However, the increase in [Ca2+]i is higher in DOCA aortic cells possibly due to
      an impairment in the mechanisms that control [Ca2+]i. The large increase in
      [Ca2+]i in response to caffeine in DOCA cells probably reflects a greater storage
      of Ca2+ in the SR.

PMID- 9239316
TI  - Worker honeybee hemolymph lipid composition and synodic lunar cycle
      periodicities.
AB  - The aim of the present investigation was to extend a previous study, showing a
      correlation of the variations of hemolymph carbohydrates with synodic lunar-like
      cycle and its circaseptan harmonics to worker honeybee hemolymph lipids.
      Hemolymph lipid concentrations of emerging worker imagos were analyzed in terms
      of one ideal synodic lunar cycle and processed by the cosinor method testing the
      null hypothesis versus the presence of 29.5-, 14.8- or 7.4-day periods in the
      data. A rhythmicity statistically compatible with a 29.5-day rhythm was observed
      for triacylglycerols and steroids as well as for body weight. A circadiseptan
      rhythm was determined for 1,3 diacylglycerols, while fatty acids and
      phospholipids exhibited a circaseptan rhythm. An agreement of peaks for
      triacylglycerols, steroids and body weight at the new moon, but not at the full
      moon, was noted with respect to trehalose and glucose circadiseptan rhythms. The
      latter moon-phase timing of peaks and nadirs, compared with that previously
      determined for trehalose and glucose, appeared to be identical to the
      circadiseptan rhythm and reciprocal for the circaseptan rhythms of 1,3
      diacylglycerols. Reciprocal tendencies in circaseptans of trehalose and glucose
      on the one hand, and fatty acids and phospholipids on the other are indicated.
      The underlying causal nexus of these relationships is unknown.

PMID- 9239318
TI  - Drug expenditures for hypertension: an empirical test of an economic model in a
      French population.

PMID- 9239317
TI  - [To be born without risk: searching for small maternity centres].
AB  - In 1992, in the public sector, 18% of child deliveries took place in small
      maternity centres having less than 15 beds. In 1981, the percentage has fallen to
      11%. In the private sector, the two proportions were respectively 30% and 11%.
      From the demographic point of view, the process of urbanization and the sharp
      decrease in the overall birth rate explain the trend. From the medical point of
      view, as the small maternities cannot have sophisticated equipment, the risk to
      the mother and the child is likely far greater than in maternities in large
      cities. However, there is no clear-cut empirical evidence. Moreover, the closing
      down of a maternity centre in a small city means loss of individual jobs, of
      collective prestige and the start of overall decline. Furthermore, people have a
      greater felling of safety with a neighboring maternity centre. In France, the
      subject is extremely controversial. The article shows some directions to cope
      with the debates.

PMID- 9239320
TI  - Active rat aromatic-L-amino acid decarboxylase as a fusion protein in Escherichia
      coli.
AB  - The DNA sequence encoding rat aromatic-L-amino acid decarboxylase (AADC) was
      inserted into the Escherichia coli (E. coli) expression vector pMAL-c2. This
      clone produced a fusion protein able to catalyze the conversion of L-DOPA to
      dopamine. After purification and treatment of the fusion protein by factor Xa
      (FXa), an enzymatically active form of the enzyme resistant to FXa was isolated.
      It showed kinetic constants, Vmax, K(m) and enzymatic properties very similar to
      those obtained previously for the mammalian enzyme. This method for obtaining
      active AADC appears to be useful for initiating the study of the catalytic
      activity of this protein because it permitted the rapid isolation and the
      stabilization of an active form of the enzyme.

PMID- 9239319
TI  - [The educated societies and the development of medical evaluation].
AB  - The French National Agency for Medical Evaluation (ANDEM) is regularly
      cooperating with scientific societies. In 1995, for the clinical guidelines and
      medical references program, ANDEM sent a request to 167 scientific societies.
      Societies were asked to select topics in which they had an involvement, to
      provide their guidelines, or recommendations they published, and to provide
      experts' names. 73 (44%) out of 167 scientific societies answered: 53 (77%) out
      of the 73 proposed themes, 20 (27%) sent a documentation, and 53 (73%) provided
      experts' names. Twenty (27%) out of the 73 wished to cooperate with ANDEM to
      draft clinical guidelines. Thirty (41%) out of the 73 gave a similar answer with
      less information. Twelve wished to cooperate but did not show any evidence for
      such a goal. The answering lag time, the presence of scientific society headings
      on the letter, the absence of arguments against the request showed that some
      scientific societies were better organized. It seems that many scientific
      societies did not have a good organization to efficiently answer to ANDEM
      request; they have not sufficient resources to afford all their objectives.
      Learned societies are not well defined, and their functioning is unknown. They
      wish to be recognized by professionals, institutions and all organizations. The
      scientific production does not seem to be much developed, even if such production
      is their first objective.

PMID- 9239321
TI  - [Decrease of supercooling capacity during embryogenesis and larval growth in
      Coleoptera].
AB  - Potential cold resistance of non-diapause eggs and first instar larvae of
      Osmoderma eremita (Coleoptera, Cetoniidae, Trichiinae) during embryogenesis and
      post-embryonic growth was assessed by measuring individual supercooling points
      (SCP): sterile eggs had a mean SCP of -24.3 +/- 2.0 degrees C; fertilized newly
      laid eggs a mean SCP of -23.4 +/- 3.2 degrees C and eggs about to hatch a mean
      SCP of -9.2 +/- 2.9 degrees C. Water absorption by fertilized eggs is a necessary
      requirement for the development of the embryo and results in an increase in
      weight and water content: fertilized newly laid eggs had a mean fresh weight of
      10.687 +/- 1.072 mg and a mean water content (expressed as a percentage of the
      dry weight) of 79.5 +/- 10.83%; eggs about to hatch had a mean fresh weight of
      19.127 +/- 3.183 mg and a mean water content of 250.10 +/- 74.15%. The ex-ovo
      larvae, hatched 30 days after oviposition, had a mean SCP of -10.1 +/- 3.6
      degrees C (no significant difference with eggs about to hatch) and had gained in
      weight (24.845 +/- 3.911 mg) and in water content (499.72 +/- 55.49%). Feeding
      1st instar larvae had a decreased supercooling ability (mean SCP = -5.7 +/- 0.4
      degrees C) whereas their mean fresh weight (99.858 +/- 53.091 mg) and mean water
      content (665.83 +/- 82.74%) increased. The eggs and larvae of O. eremita are
      freezing intolerant. Before overwintering, all larvae switch to being freezing
      tolerant and can survive ice formation in their tissues and body fluids, whereas
      their mean SCP stays at around -5 degrees C. However, recent experiments in the
      winter of 1996 have shown that frozen larva mortality does occur at temperatures
      lower than about -12 degrees C.

PMID- 9239322
TI  - Wortmannin inhibits IGF-dependent differentiation in the mouse myogenic cell line
      C2.
AB  - Evidence has accumulated that suggests that insulin-like growth factors (IGFs)
      exert a positive influence on myoblast differentiation. We have undertaken to
      study the signalling events required for differentiation resulting from type-1
      IGF receptor stimulation in C2 myoblasts, where autocrine production of IGF-II
      was abolished by means of antisense RNA. Exposure of the cells to IGFs leads to a
      rapid and sustained activation of phosphatidyl-inositol 3-kinase followed by the
      expression of Myod, myogenin and differentiation. The fungal metabolite,
      wortmannin, inhibits both PI 3-kinase and muscle differentiation with an IC 50 in
      the nanomolar range. IGFs are also known to cause a rapid activation of MAP
      kinase. However, the synthetic inhibitor of MEK, PD098059, which prevents MAP
      kinase activation, does not affect myoblast differentiation. These results
      provide evidence that PI 3-kinase, but not MAP kinase, is required for insulin
      like growth factor receptor-dependent differentiation of muscle cells.

PMID- 9239323
TI  - Serial learning in the pigeon in a free correction procedure: role of reinforcing
      values.
AB  - Pigeons were shown four chromatic stimuli simultaneously (A, B, C, D) in daily 15
      min sessions. A free correction procedure was used: production of the series A-
      >B-->C resulted in food delivery and ended a trial, while incorrect colour pecks
      had no consequences. The learning criterion (five consecutive correct series) was
      not achieved after 50 sessions, although the number of correct responses
      increased progressively. From around session 10, birds produced primarily
      transitions between items B and C or A and C and repeats on items B and C (BC
      35%, AC 15%, BB 10%, CC 25%). Despite the low rate of the previously acquired A-
      >B transition (6%), its production was highly correlated with that of the A-->B-
      >C series. On the other hand, item C was predominantly pecked and a recency
      effect occurred for this item. These data extend previous findings indicating
      that acquisition of series in pigeons involves the formation of associative links
      between stimuli according to direct and indirect reinforcing values.

PMID- 9239324
TI  - [Fetomaternal tolerance: role of HLA-G molecule in the protection of the fetus
      against maternal natural killer activity].
AB  - HLA-G is a non-classical major histocompatibility complex class I molecule
      selectively expressed on extravillous trophoblast cells at the fetal-maternal
      interface. HLA-G may play an important role in maintaining maternal immune
      tolerance of the semi-allogenic fetus. In this study, we demonstrate for the
      first time the protective role of HLA-G during pregnancy. Indeed, cytotrophoblast
      cells of the fetus are resistant to lytic activity by maternal decidual natural
      killer cells. In order to precisely characterize the immunological functions of
      HLA-G products, we have investigated the protective role of the membrane-bound
      HLA-G1 and HLA-G2 isoforms against NK cell cytotoxicity. For this purpose, HLA-G1
      and HLA-G2 cDNAs were transfected into the HLA-class I negative human K562 cell
      line. We demonstrate that both HLA-G1 and HLA-G2 transfectants inhibit NK
      cytolysis observed in peripheral blood from 25 donors (males and females). This
      led us to the conjecture that HLA-G is the public ligand for natural killer
      inhibitory receptors present in all individuals.

PMID- 9239325
TI  - Hypothesis: the meeting place model for prion disease.
AB  - Prions are responsible for spongiform diseases such as scrapie and bovine
      spongiform encephalopathy. It is now generally accepted that the disease
      mechanism involves the conversion from the normal form, PrPC, to the pathogenic
      form, PrPSc, and that this isoform is infectious. In the case of scrapie, 15
      different forms of the disease have been described and some of these different
      phenotypes can be conferred by infectious prions that are themselves encoded by
      normal genes. We propose here that a prion with an altered structure has a
      correspondingly altered preference for lipids; this altered preference creates a
      proteolipid domain containing different lipids and other factors such as
      chaperonins and enzymes responsible for post-translational modifications. Normal
      prions associated with this abnormal domain adopt the conformation dictated by
      its lipidic composition (and by the other factors present) and so acquire the
      lipidic preference of the original pathogenic prions. These transformed prions
      could then create new proteolipid domains. This process may be considered as semi
      conservative replication in which prion and lipids are analogous to the Watson
      and Crick strands and the proteolipid domain to the double helix itself.

PMID- 9239326
TI  - [Main trends in universal imaging in 1997].

PMID- 9239327
TI  - [Telecommunication networks and PACS].

PMID- 9239328
TI  - [Magnetic resonance imaging].

PMID- 9239329
TI  - [X-ray computed tomography].

PMID- 9239330
TI  - [Conventional and vascular digital radiology].

PMID- 9239331
TI  - [Ultrasonography].

PMID- 9239332
TI  - [Films and related devices].

PMID- 9239333
TI  - [Nuclear medicine].

PMID- 9239334
TI  - [Equipments of quality control].

PMID- 9239335
TI  - [Mammography. Still at the technological advant-guard].

PMID- 9239336
TI  - [MRI of the pulmonary parenchyma. Clinical value and research prospects].
AB  - MR imaging of the lung is handicapped by three negative influences. First, the
      low proton spin density in lung tissue results in a low signal-to-noise ratio
      relative to the surrounding structures. Second, cardiac and respiratory motion
      induce artifacts that tend to obscure fine structural detail in the lung. Third,
      a considerable magnetic susceptibility gradient, arising from the large surface
      areas of air and tissue interfaces, produces a very low value for T2*. MR imaging
      can be used to stage the activity of interstitial lung disease and for the
      diagnosis of lipoid pneumonia and pulmonary infarction. In combination with MR
      angiography, perfusion MR imaging might eventually become a test for pulmonary
      embolisms.

PMID- 9239338
TI  - [Anatomical study with MRI of a small muscle: the masseter].
AB  - Magnetic resonance imaging (MRI) provides functional information in an anatomic
      presentation allowing to distinguish soft tissues with high sensitivity. The goal
      of this study was to investigate the normal anatomy of the major masticatory
      muscle, the masseter, both at rest or during contraction by using three
      dimensional (3D) MRI. Eighteen subjects aged from 19 to 28 years, all in good
      health, were studied. Several experiments were first realized on phantoms to test
      the 3D-MRI technique. After reconstruction and segmentation processing, 3D
      acquisition, enabled obtaining data on the masseter anatomy. The normal
      anatomical position of the masseter was reported to the skin plan as the mean
      internal distance (7.9 +/- 0.42 mm) and external distance (15.2 +/- 0.41 mm).
      While there was no difference between internal distance, for sex or side, the
      external distance was significantly (p = 0.02) shorter in male (7.7 +/- 0.5 mm)
      than in female (8.8 +/- 0.4 mm) for both sides. The mean volume for all subjects
      and both sides (20.3 +/- 1.1 cm3) did not change significantly between rest and
      exercise. The masseter volume was significantly (p < 0.00001) greater in male
      (24.2 +/- 2.0 cm3) than in female (16.4 +/- 3.6 cm3) groups. These physiological
      references may be useful for further MRI investigations of masticatory system
      pathologies.

PMID- 9239337
TI  - [Longitudinal splitting syndrome of the short fibular tendon. . Imaging and
      classification by MRI].
AB  - We present a series of 38 cases of longitudinal splitting of the peroneus brevis
      tendon revealed by MR imaging (12 lesions were confirmed at surgery). MRI enabled
      classification in four surgical grades. The frequency of such lesions in chronic
      ankle instability as observed in our series is often reported in the literature.
      Bilateral cases are common. Asymptomatic cases do occur, especially in grades I
      and II. MRI has been shown to be a very effective investigation for demonstrating
      this tendinous lesion; the proton density weighted sequence in the axial plane is
      the most adequate sequence.

PMID- 9239339
TI  - [Management of anxious and painful manifestations in pediatric uroradiology].
AB  - Two hundred and seven children undergoing either intravenous pyelography (i.v.p.)
      or voiding cystourethrography (VCUG) were examined. Under the age of 5 years,
      children received intra-rectal midazolam (0.5 mg/kg) with a maximum of 5 mg.
      Children over 5 years, self-inhaled an equimolar mixture of oxygen and nitrous
      oxide. Pain and stress were evaluated in children under 5, by the pediatric
      radiologist according to the 4 non verbal items of the Le Baron-Zeltzer scale and
      in children over 5 by the child himself with a visual analogic scale. Under 5
      years of age, midazolam significantly reduced pain and stress during i.v.p. (p <
      0.0001), VCUG both in boys (p < 0.0001) and girls (p < 0.0001). In children over
      5, nitrous oxide inhalation reduced pain during i.v.p. (p = 0.0004), during VCUG
      in girls (p = 0.0025), but not in boys ((p > 0.05). Pediatric radiologists should
      evaluate pain and stress in their patients as they can be easily and safely
      limited.

PMID- 9239340
TI  - [Septic arthritis of posterior lumbar facet joint].
AB  - Septic arthritis of the posterior lumbar joints is extremely rare. The clinical
      picture of this unusual site of infection can easily lead to confusion with
      spondylodiscitis which is more common. We report a case of a 50-year-old woman
      with Staphylococcus aureus septic arthritis of the left L5-S1 lumbar facet joint.
      CT scan was helpful to establish the diagnosis and to guide the percutaneous
      needle biopsy.

PMID- 9239341
TI  - [Angiographic identification of spinal cord arteries before bronchial artery
      embolization].
AB  - Ischemic spinal cord injury is the major risk of bronchial artery embolization.
      The spinal artery may be overlooked on initial intercostobronchial trunk
      arteriography, as a result of reverse flow within the intercostal branch. Its
      identification, conversely, is easier on postembolization angiography. An
      illustrative case is presented, with angiographic correlation. The
      pathophysiology of the reverse flow is discussed. Technical recommendations are
      proposed for its detection.

PMID- 9239342
TI  - [Giant hepatic hemangioma causing dilatation of the intrahepatic biliary ducts].
AB  - Giant hepatic hemangiomas are rare entities. They can be symptomatic with pain
      and increased erythrocyte sedimentation rate. Cholestasis has already been
      reported. We describe a case of biliary dilatation secondary to a hemorrhagic
      giant hepatic hemangioma documented on CT and MRI.

PMID- 9239343
TI  - [Orbital metastases of melanoma of the choroid. Value of imaging].
AB  - Choroidal melanoma is characterized by an unpredictable clinical course, during
      which metastatic disease may occur after a prolonged disease-free interval.
      However, metastases to orbit are quite rare; there have been only 6 reported
      cases in the literature. We report well documented examples of metastases to the
      orbit from a melanoma of the choroid first diagnosed 8 years earlier. MR imaging
      is accurate in determining the exact location of lesions and their nature owing
      to the paramagnetic properties of melanin.

PMID- 9239344
TI  - [Appendicitis in the sub-hepatic site].

PMID- 9239345
TI  - [Value of percutaneous injection of acrylic cement using a pressure regulator].
AB  - Injection of acrylic glue, especially in its watery phase, remains difficult,
      even with small syringes. The use of a pressure regulator similar to those used
      for balloon inflating in vascular radiology makes this procedure easier, reducing
      the risk of glove perforation, with optimal precision and safety.

PMID- 9239346
TI  - [The virtual university: education in the 3rd millennium?].

PMID- 9239347
TI  - [Value of automated medical indexing of an image database and a digital
      radiological library].
AB  - We indexed the contents of a radiology server on the web to facilitate access to
      research documents and to link reference texts to images contained in radiology
      databases. Indexation also allows case reports to be transformed with no
      supplementary work into formats compatible with computer-assisted training.
      Indexation was performed automatically by ADM-Index, the aim being to identify
      the medical concepts expressed within each medical text. Two types of texts were
      indexed: medical imaging reference books (Edicerf) and case reports with
      illustrations and captions (Iconocerf). These documents are now available on a
      web server with HTML format for Edicerf and on an Oracle database for Iconocerf.
      When the user consults a chapter of a book or a case report, the indexed terms
      are displayed in the heading; all reference texts and case reports containing the
      indexed terms can then be called up instantaneously. The user can express his
      search in natural language. Indexation follows the same process allowing
      instantaneous recall of all reference texts and case reports where the same
      concept appears in the diagnosis or clinical context. By using the context of the
      case reports as the search index, all case reports involving a common medical
      concept can be found. The context is interpreted as a question. When the user
      responds to this question, ADM-Index compares this response with the answer
      furnished by the reference texts and case reports. Correct or erroneous responses
      can thus be identified, converting the system into a computer-assisted training
      tool.

PMID- 9239348
TI  - [Psychological behavior of patients in MRI: analysis, proposals for improvement
      and contribution of open magnet equipment].
AB  - Many patients report anxiety during MR imaging. Anxiety is due to immobility,
      coil noise, high temperature, duration of the examination and shape of the
      system. On basis of a prospective series of 250 patients undergoing MR studies,
      we have analysed mechanisms and reasons of anxiety. Psychological strategies are
      useful to reduce anxiety and improve patients' cooperation and relaxation. The
      easiest and most effective way is to inform the distressed patient. Information
      about the MRI examination must be clear and simple. Open field magnets improve
      comfort and global conditions of the examination realisation. Psychological
      consequences are less important. Open field MR systems reduce claustrophobia
      induced by MR imaging.

PMID- 9239349
TI  - [Mesenteric and portal venous gas in infarction of the small intestine in adults.
      Apropos of 3 clinical cases. Value of x-ray computed tomography].
AB  - Three case reports are presented with mesenteric and portal venous gas secondary
      to mesenteric infarction. In these patients with ileus, abdominal CT Scan appears
      as the most reliable diagnosis procedure. It can detect intravascular gas but
      also abnormalities of the intestinal wall such as intramural gas even without
      contrast. In mesenteric infarction, mesenteric and portal venous gas are
      radiological signs which considerably worsen the prognosis.

PMID- 9239350
TI  - [Magnetic resonance imaging in meniscal bucket-handle tears].
AB  - PURPOSE: To define MR signs of meniscal bucket-handle tears and evaluate the
      diagnostic efficiency of this technique. MATERIALS AND METHODS: Retrospective
      study of 30 patients with a meniscal bucket-handle tear and 30 with a different
      type of tear, all proven by arthroscopy. The following MR signs of a bucket
      handle tear were evaluated: "separate meniscal fragment", "double posterior
      cruciate ligament", "snake sign" and "double anterior hom". RESULTS: A correct
      diagnosis of a bucket-handle tear was only made in 18/30 of patients. Several of
      the MR signs were seen in the same patient in 17 cases. A double posterior
      cruciate ligament was present only in cases of medial meniscus tears. The 12
      menisci without these signs, and therefore not diagnosed as bucket-handle tears,
      were all classified as meniscal tears on the basis of signal extending to the
      meniscal surface. Nine of these were not displaced into the intercondylar notch
      at arthroscopy. The interobserver agreement was excellent: kappa = 0.88.
      CONCLUSION: The diagnosis of a bucket-handle meniscal tear, if it is displaced,
      can be made when one or more of the four MR evaluated signs are present. Other
      forms of meniscal tears are only exceptionally diagnosed as bucket-handle tears.

PMID- 9239351
TI  - [Imaging aspect of a case of fibrodysplasia ossificans progressiva].
AB  - Fibrodysplasia ossificans progressiva is a rare congenital disease that affects
      children under the age of five years. Soft tissue swelling of the cervical and
      dorsal regions with local pain, warmth and low grade fever are the early clinical
      manifestations, usually associated with hallux valgus and microdactily of the
      fingers and toes. Calcifications of the fascias and muscles cause muscular
      contractures leading to progressive disability and restrictive lung disease. In
      the early stage, CT shows edema of the soft tissues and later on, calcifications
      of muscular fascia. The association of these radiographic and CT findings is
      specific and should avoid muscular biopsies which are known to be an aggravating
      factor in this disease.

PMID- 9239352
TI  - [Imaging of prostatic leiomyosarcoma and contribution of MRI].
AB  - A case of leiomyosarcoma of the prostate is presented. Adult prostatic
      leiomyosarcoma is a rare tumor with a poor prognosis. US-CT and MRI findings are
      described.

PMID- 9239353
TI  - [Axillary lymph node microcalcifications disclosing breast cancer].
AB  - Intra nodal calcifications associate with breast cancer are uncommon. The rare
      publications always describe malignant microcaocifications in axillary lymph
      nodes, evolving with the primary breast tumor imaged on mammography. In the
      reported observation, we observed calcified metastatic neoplasm in axillary
      nodes, preceding the intramammary lesion.

PMID- 9239354
TI  - [Osteosarcoma of the mandible].
AB  - We describe a case of osteosarcoma of the mandible presenting as a soft tissue
      mass associated with an enlargement of the mandibular canal at imaging work-up.
      Radiographic, isotopic, CT and MR features are reported.

PMID- 9239355
TI  - [Devic's neuromyelitis optica].

PMID- 9239356
TI  - [Hepatic abscess with hepato-bronchial fistula].

PMID- 9239357
TI  - [Has functional cerebral MRI a clinical future?].

PMID- 9239358
TI  - [Parameters influencing hepatic parenchyma enhancement in x-ray computed
      tomography after intravenous injection of iodinated contrast medium].
AB  - With the widespread use of spiral CT, a complete reassessment of intravenous
      injection of contrast material for body computed tomography is necessary. An
      optimal administration of contrast material with respect to scan timing is indeed
      more critical with spiral CT. Numerous factors affect hepatic contrast
      enhancement time-attenuation curves after injection of contrast material into a
      peripheral vein. Some are patient related, while other result from the modalities
      of administration of the iodinated agent. The objective of this article is to
      review the most contributive factors in liver enhancement after iodine injection.
      Knowledge of these factors can optimize the use of spiral CT, with the expected
      benefit of saving costs in contrast material.

PMID- 9239359
TI  - [Scanner or dynamic MRI in hepatic study. An audacious plan for an avoidable
      war].

PMID- 9239360
TI  - [Ultrasonography of acute osteomyelitis of the long bones in children. Diagnostic
      and prognostic value].
AB  - Between 1991 and 1994, ultrasonography was used to investigate 90 consecutive
      children with acute osteomyelitis. Ultrasonographic findings were analyzed taking
      into account the time elapsed from first symptoms. Outcome in 47 children who
      were treated and followed for at least 6 months was also studied. Deep soft
      tissue swelling adjacent to the affected bone was found to be an early but
      nonspecific sign which persisted all along the course of the disease. Periosteal
      elevation smaller than 3 mm, secondary to exsudation or septic fluid, confirmed
      the disease in earliest stage and was the most frequent ultrasonographic sign in
      first three days of disease. Treated at that stage, total resolution was obtained
      in 66% of patients and stabilization, in 34% of cases, without any evolution
      toward chronicity. Acute osteomyelitis with subperiosteal abscess progressed
      toward stabilization in 66% of cases and toward chronic osteomyelitis in 8% of
      cases. 32% of subperiosteal abscess were ruptured; in such situation, progression
      to chronicity was observed in 26% of patients. Since ultrasonography has been
      used in our institution for the diagnosis of acute osteomyelitis, the rate of
      evolution to chronicity spectacularly dropped from 63% to 11%. The main advantage
      of ultrasonography is an earlier detection of subperiosteal collection that
      indicates surgical drainage without any delay.

PMID- 9239361
TI  - [Diagnostic imaging of acute osteomyelitis in children].

PMID- 9239362
TI  - [Aseptic osteonecrosis of the femoral condyle after meniscectomy by the
      arthroscopic approach].
AB  - Retrospective review of 10 patients who presented with avascular necrosis of the
      ipsilateral femoral condyle following arthroscopic meniscectomy (9 medial, 1
      lateral). The bone lesions were evaluated by radiography and MRI, which were
      repeated for few patients. MRI allows earlier diagnosis of avascular necrosis of
      the femoral condyle and offers an evaluation of extent of the lesions whose
      evolution is variable: 3 patients required a knee prothesis, the other 7 patients
      were treated medically.

PMID- 9239363
TI  - [Doppler ultrasonography in the study of the vascularization of the femur head in
      newborn infants].
AB  - PURPOSE: To establish the effectiveness of color Doppler and power Doppler
      ultrasound (US) in identifying the arterial supply of the femoral head in
      newborn. MATERIAL AND METHODS: Sixty normal hips in 30 newborns (mean age: 22
      days) were imaged with a 7 MHz transducer. The presence and Doppler
      characteristics of flow in the branches of the inferior and superior arterial
      groups were documented according to the anatomic description of Lagrange and
      Dunoyer. RESULTS: The arterial flow within the chondroepiphysis from the inferior
      and superior branches was visualized in 100% and 91% cases, respectively. The
      transversal trochanter major incidence was the most adequate. Abduction without
      stress did not induce modification of the arterial supply. CONCLUSION:
      Visualization of femoral head vascularity with Power Doppler and color Doppler US
      is feasible and consistent in the majority of healthy neonates.

PMID- 9239364
TI  - [Diagnosis of infraclinical lesions of the breast with dynamic MRI: results of a
      prospective and multicenter study].
AB  - AIM: To determine the accuracy of dynamic contrast-enhanced subfraction MRI to
      diagnose nonpalpable breast lesions in a prospective multicenter study. MATERIAL
      AND METHODS: From June to November 1994, 72 patients had a surgical biopsy for a
      nonpalpable breast lesion and a preoperative dynamic MR after an informed consent
      was obtained. MR examinations were performed on 0.5, 1 and 1.5T MR unit. Each
      center underwent dynamic sequences either in spin or gradient echo in T1 weighted
      images obtained in less than two minutes before and after injection of Gadolinium
      DOTA. The presence/absence of contrast enhancement within two minutes after
      injection of Gadolinium were considered as positive/negative findings
      respectively. RESULTS: These 72 women had mammographic (n = 80) or
      ultrasonographic lesions (n = 2). Mammograms showed mass (n = 23), asymmetrical
      density (n = 2), architectural distorsion (n = 8), clustered microcalcifications
      (n = 47) or was normal (n = 2). Dynamic Breast MR imaging showed early contrast
      enhancement in 44 malignant lesions (sensitivity: 89.8%) and 13 benign lesions
      (specificity: 60.6%). Five intraductal carcinoma of comedo (n = 1) or non-comedo
      (n = 4) type did not demonstrate any early contrast enhancement. CONCLUSION: This
      prospective mulcentric study confirms the high sensitivity of dynamic breast MRI
      whatever the type of MR unit or sequences.

PMID- 9239365
TI  - [Primary bilateral adrenal lymphoma as viewed by MRI. Apropos of a  case].
AB  - Clinically silent adrenal involvement in lymphoma is a relatively common
      occurrence, involvement of bilateral adrenal glands by lymphoma as the sole
      manifestation of lymphoma is very rare, with only 30 cases reported in the
      literature. We report a patient with this unusual conditions, with CT scan and
      MRI aspects.

PMID- 9239366
TI  - [Hypertrophic osteoarthropathy associated with malignant thymoma in a child].
AB  - We report a case of pulmonary hypertrophic osteoarthropathy in a child with
      malignancy thymoma. This entity is infrequent in pediatric patients.

PMID- 9239367
TI  - [Mesenteric panniculitis. Aspects in x-ray computed tomography and MRI].
AB  - We report one case of mesenteric panniculitis. This rare and poorly-known disease
      is characterized by a non specific inflammatory process involving adipose tissue
      of the mesentery. The new imaging techniques (CT and MRI) may be helpful for the
      diagnosis of this disease and allow avoiding laparotomy. However histological
      proof remains necessary and can be given by guided needle biopsy.

PMID- 9239368
TI  - [Agenesis of the diaphragm in a young adult. Apropos of a case].
AB  - We report a case of asymptomatic right diaphragm agenesis, in a 20-year-old adult
      hospitalized for internal bleeding. This kind of malformation is rare,
      particularly in adults thus it must be recognized. Imaging modalities are the
      main tool for diagnosis. It may be suggested by chest X-Ray US, baryum
      opacification and CT allow to establish a definite diagnosis depicting the
      herniated organs. The treatment is surgical and the prognosis is in general good.

PMID- 9239369
TI  - [Ultrasonic diagnosis of placenta percreta. Apropos of a case with hemorrhagic
      complication].
AB  - Placenta percreta is a rare but severe disease, which is more and more frequent.
      The reported case shows that diagnosis can be made with B mode and color Doppler
      ultrasonography. Extension of high-vascularized placenta to the myometrium,
      abnormal placental-subplacental complex and vascular flow through the myometrium
      were suggestive of the diagnosis. Early diagnosis should decrease mortality and
      morbidity.

PMID- 9239370
TI  - [Calcified aneurysm of the right renal artery].

PMID- 9239371
TI  - [Recommendations of the Consensus Conference on Imaging of mechanical and
      degenerative pathology of a non-operated shoulder].

PMID- 9239372
TI  - [Epidemiology of hepatitis C in 1997 in France].

PMID- 9239373
TI  - [Clinical aspects and course of viral hepatitis C].

PMID- 9239374
TI  - [Pathology of the hepatitis C virus: histopathological aspects].

PMID- 9239375
TI  - [Extrahepatic manifestations of the hepatitis C virus].

PMID- 9239377
TI  - [From physiology to pharmacology: the points of impact of antithrombotic agents].

PMID- 9239378
TI  - [Antivitamin K, aspirin: treatments still of significance].

PMID- 9239379
TI  - [Dyslipidemia and thrombosis: what role for therapeutics?].

PMID- 9239376
TI  - [Treatments of hepatitis C].

PMID- 9239380
TI  - [Leaving the table on the knees!].

PMID- 9239381
TI  - [A herpes not so simplex].

PMID- 9239382
TI  - [Occlusive syndrome and hypersideremic anemia].

PMID- 9239383
TI  - [After winter ... springtime].

PMID- 9239384
TI  - [A rare cause of chronic diarrhea].

PMID- 9239385
TI  - [Fatal edematous polyarthritis].

PMID- 9239386
TI  - [Diarrhea syndrome under corticoid therapy].

PMID- 9239387
TI  - [False membranes and diplopia].

PMID- 9239388
TI  - [Depressive status, rhabdomyolysis and inflammatory syndrome in a 71-year-old
      patient].

PMID- 9239389
TI  - [Fever, acute colitis and renal insufficiency in a 44-year-old woman].

PMID- 9239390
TI  - [Dementia syndrome of recent appearance...].

PMID- 9239391
TI  - [Uncommon familial disease of female transmission].

PMID- 9239392
TI  - [Rebounding hyperthyroidism].

PMID- 9239393
TI  - Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to
      selectins in leukocyte recruitment.

PMID- 9239394
TI  - Perspectives series: host/pathogen interactions. Apoptosis in bacterial
      pathogenesis.

PMID- 9239395
TI  - The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for
      HIV-1 infection.
AB  - The chemokines are a homologous serum protein family characterized by their
      ability to induce activation of integrin adhesion molecules and leukocyte
      migration. Chemokines interact with their receptors, which are composed of a
      single-chain, seven-helix, membrane-spanning protein coupled to G proteins. Two
      CC chemokine receptors, CCR3 and CCR5, as well as the CXCR4 chemokine receptor,
      have been shown necessary for infection by several HIV-1 virus isolates. We
      studied the effect of the chemokine monocyte chemoattractant protein 1 (MCP-1)
      and of a panel of MCP-1 receptor (CCR2)-specific monoclonal antibodies (mAb) on
      the suppression of HIV-1 replication in peripheral blood mononuclear cells. We
      have compelling evidence that MCP-1 has potent HIV-1 suppressive activity when
      HIV-1-infected peripheral blood lymphocytes are used as target cells.
      Furthermore, mAb specific for the MCP-1R CCR2 which recognize the third
      extracellular CCR2 domain inhibit all MCP-1 activity and also block MCP-1
      suppressive activity. Finally, a set of mAb specific for the CCR2 amino-terminal
      domain, one of which mimics MCP-1 activity, has a potent suppressive effect on
      HIV-1 replication in M- and T-tropic HIV-1 viral isolates. We conjecture a role
      for CCR2 as a coreceptor for HIV-1 infection and map the HIV-1 binding site to
      the amino-terminal part of this receptor. This concurs with results showing that
      the CCR5 amino terminus is relevant in HIV-1 infection, although chimeric fusion
      of various extracellular domains shows that other domains are also implicated. We
      discuss the importance of CCR2 structure relative to its coreceptor role and the
      role of anti-CCR2 receptor antibodies in the prevention of HIV-1 infection.

PMID- 9239396
TI  - Human histocompatibility leukocyte antigen-binding supermotifs predict broadly
      cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis.
AB  - The present study was designed to determine if highly conserved hepatitis B virus
      (HBV)-derived peptides that bind multiple HLA class I alleles with high affinity
      are recognized as cytotoxic T lymphocyte (CTL) epitopes in acutely infected
      patients. Peripheral blood mononuclear cells from 67 patients with acute
      hepatitis B, and 12 patients convalescent from acute hepatitis B, were stimulated
      with three panels of peptides, each of which bind with high affinity to several
      class I alleles from the HLA-A2-, HLA-A3-, or HLA-B7-supertypes. In these
      patients, 8 of the 19 peptides tested were found to represent CTL epitopes
      recognized by two or more alleles in each supertype. Two sets of nested peptides
      were recognized in the context of alleles with completely unrelated peptide
      binding specificities. Finally, promiscuous recognition by the same CTL of a
      given peptide presented by target cells expressing different A2 subtypes was also
      commonly observed. In conclusion, several HBV-specific CTL epitopes, recognized
      by acutely infected or convalescent patients in the context of a wide range of
      HLA alleles have been identified. These results demonstrate the functional
      relevance of the supertype grouping of HLA class I molecules in a human viral
      disease setting. Furthermore, they represent a significant advance in the
      development of a totally synthetic vaccine to terminate chronic HBV infection and
      support the feasibility of a systematic approach to development of similar
      vaccines for prevention and treatment of other chronic viral infections.

PMID- 9239397
TI  - Cloning, characterization, and functional studies of a nonintegrin platelet
      receptor for type I collagen.
AB  - A cDNA (1.6 kb) encoding a platelet protein receptor that binds type I collagen
      has been isolated from a human bone marrow cDNA library by using a degenerate
      oligonucleotide probe derived from the amino acid sequence of a CNBr fragment of
      the purified receptor. Computer search revealed that this cDNA represents the
      coding sequence of a unique protein. Using the prokaryotic expression system pKK
      223-3-65 cDNA, a 54-kD recombinant protein was obtained and purified to apparent
      homogeneity. In an eukaryotic expression vector (pcDNA3-65 cDNA), a 65-kD protein
      was identified that was recognized by monoclonal anti-65 kD antibody (anti-65m).
      The recombinant protein binds to type I, but not to type III collagen by affinity
      column chromatography. The binding of the recombinant protein to type I collagen
      coated Petri dishes is inhibited by anti-65m in a dose-dependent manner. The
      pcDNA3-65 cDNA-transfected nonadherent T cells express the protein, allowing them
      to attach to a type I collagen matrix, and are inhibited by anti-65m in a dose
      dependent manner. Like the receptor protein purified from platelet membranes, the
      recombinant protein inhibits type I collagen-induced platelet aggregation and the
      adhesion of [14C]serotonin-labeled platelets to type I collagen in a dose
      dependent manner. The recombinant protein neither binds to type III collagen
      coated Petri dishes nor inhibits type III collagen and ADP-induced platelet
      aggregation, indicating specificity for type I collagen.

PMID- 9239398
TI  - Prevention of In vitro neutrophil adhesion to endothelial cells through shedding
      of L-selectin by C-reactive protein and peptides derived from C-reactive protein.
AB  - C-Reactive protein (CRP), the classic acute-phase reactant in humans, diminishes
      accumulation of neutrophils at inflammatory sites. To evaluate the underlying
      mechanisms, we have studied whether CRP and peptides derived from CRP could
      affect the first step of neutrophil extravasation, the L-selectin-mediated
      interaction of neutrophils with endothelial cells. CRP markedly attenuated
      attachment of human neutrophils to cultured LPS-activated human coronary artery
      and pulmonary microvascular endothelial cells with apparent IC50 values of 20 and
      22 microg/ml, respectively. At similar concentrations, CRP rapidly downregulated
      the expression of L-selectin on the neutrophil surface, whereas it failed to
      affect expression of CD11b and CD45 or to induce granule enzyme release. The loss
      of L-selectin was due to cleavage and shedding of the molecule from the cell
      surface, as quantitated by the soluble form of L-selectin in cell-free
      supernatants. The effects of CRP could be prevented by an anti-CRP antiserum and
      by KD-IX-73-4, which inhibits shedding of L-selectin. Inhibition of adhesion with
      CRP was additive with function-blocking anti-E-selectin and anti-CD18 antibodies,
      but was not additive with anti-L-selectin antibody. Neutrophil attachment and L
      selectin expression were also diminished by CRP peptides 174-185 and 201-206, but
      not peptide 77-82, albeit these peptides showed a weaker inhibitory effect than
      the parent protein. These studies indicate a specific activation-independent
      action of CRP and CRP peptides 174-185 and 201-206 on expression of L-selectin,
      and suggest that by attenuating neutrophil adhesion to the endothelium and
      consequently neutrophil traffic into tissues, native CRP and peptides 174-185 and
      201-206 may be major mechanisms to attenuate or limit the inflammatory response.

PMID- 9239399
TI  - Treatment with the oral antidiabetic agent troglitazone improves beta cell
      responses to glucose in subjects with impaired glucose tolerance.
AB  - Impaired glucose tolerance (IGT) is associated with defects in both insulin
      secretion and action and carries a high risk for conversion to non-insulin
      dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent,
      reduces glucose concentrations in subjects with NIDDM and IGT but is not known to
      affect insulin secretion. We sought to determine the role of beta cell function
      in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk
      of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a
      randomized, double-blind design. Study measures at baseline and after treatment
      were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin
      sensitivity index (SI) assessed by a frequently sampled intravenous glucose
      tolerance test, insulin secretion rates during a graded glucose infusion, and
      beta cell glucose-sensing ability during an oscillatory glucose infusion.
      Troglitazone reduced integrated glucose and insulin responses to oral glucose by
      10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to
      2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted
      for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P =
      0.02), and the ability of the beta cell to entrain to an exogenous oscillatory
      glucose infusion, as evaluated by analysis of spectral power, was improved by 49%
      (P = 0.04). No significant changes in these parameters were demonstrated in the
      placebo group. In addition to increasing insulin sensitivity, we demonstrate that
      troglitazone improves the reduced beta cell response to glucose characteristic of
      subjects with IGT. This appears to be an important factor in the observed
      improvement in glucose tolerance.

PMID- 9239400
TI  - Regulation of sodium-dependent phosphate transport in osteoclasts.
AB  - Osteoclasts are the primary cells responsible for bone resorption. They are
      exposed to high ambient concentrations of inorganic phosphate (Pi) during the
      process of bone resorption and they possess specific Pi-transport system(s)
      capable of taking up Pi released by bone resorption. By immunochemical studies
      and PCR, we confirmed previous studies suggesting the presence of an Na-dependent
      Pi transporter related to the renal tubular "NaPi" proteins in the osteoclast.
      Using polyclonal antibodies to NaPi-2 (the rat variant), an approximately 95-kD
      protein was detected, localized in discrete vesicles in unpolarized osteoclasts
      cultured on glass coverslips. However, in polarized osteoclasts cultured on bone,
      immunofluorescence studies demonstrated the protein to be localized exclusively
      on the basolateral membrane, where it colocalizes with an Na-H exchanger but
      opposite to localization of the vacuolar H-ATPase. An inhibitor of
      phosphatidylinositol 3-kinase, wortmannin, and an inhibitor of actin cytoskeletal
      organization, cytochalasin D, blocked the bone-stimulated increase in Pi uptake.
      Phosphonoformic acid (PFA), an inhibitor of the renal NaPi-cotransporter, reduced
      NaPi uptake in the osteoclast. PFA also elicited a dose-dependent inhibition of
      bone resorption. PFA limited ATP production in osteoclasts attached to bone
      particles. Our results suggest that Pi transport in the osteoclast is a process
      critical to the resorption of bone through provision of necessary energy
      substrates.

PMID- 9239401
TI  - Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial
      rejection in transplanted mouse hearts.
AB  - We have hypothesized that T cell cytokines participate in the pathogenesis of
      graft arterial disease (GAD). This study tested the consequences of IFN-gamma
      deficiency on arterial and parenchymal pathology in murine cardiac allografts.
      Hearts from C-H-2(bm12)KhEg (bm12, H-2(bm12)) were transplanted into C57/B6 (B6,
      H-2(b)), wild-type, or B6 IFN-gamma-deficient (GKO) recipients after
      immunosuppression by treatment with anti-CD4 and anti-CD8 mAbs. In wild-type
      recipients, myocardial rejection peaked at 4 wk, (grade 2. 1+/-0.3 out of 4,
      mean+/-SEM, n = 9), and by 8-12 wk evolved coronary arteriopathy. At 12 wk, the
      GAD score was 1.4+/-0.3, and the parenchymal rejection grade was 1.2+/-0.3 (n =
      8). In GKO recipients of bm12 allografts, myocardial rejection persisted at 12 wk
      (grade 2.5+/-0.3, n = 6), but no GAD developed (score: 0.0+/-0.0, n = 6, P < 0.01
      vs. wild-type). Mice treated with anti-IFN-gamma mAbs showed similar results.
      Isografts generally showed no arterial changes. In wild-type recipients, arterial
      and parenchymal cells showed increased MHC class II molecules, intercellular
      adhesion molecule-1, and vascular cell adhesion molecule-1 compared to normal or
      isografted hearts. The allografts in GKO recipients showed attenuated expression
      of these molecules (n = 6). Thus, development of GAD, but not parenchymal
      rejection, requires IFN-gamma. Reduced expression of MHC antigens and leukocyte
      adhesion molecules may contribute to the lack of coronary arteriopathy in hearts
      allografted into GKO mice.

PMID- 9239402
TI  - Modification of apolipoprotein(a) lysine binding site reduces atherosclerosis in
      transgenic mice.
AB  - Lipoprotein(a) contributes to the development of atherosclerosis through the
      binding of its plasminogen-like apolipoprotein(a) component to fibrin and other
      plasminogen substrates. Apolipoprotein(a) contains a major lysine binding site in
      one of its kringle domains. Destruction of this site by mutagenesis greatly
      reduces the binding of apolipoprotein(a) to lysine and fibrin. Transgenic mice
      expressing this mutant form of apolipoprotein(a) as well as mice expressing wild
      type apolipoprotein(a) have been created in an inbred mouse strain. The wild-type
      apolipoprotein(a) transgenic mice have a fivefold increase in the development of
      lipid lesions, as well as a large increase in the focal deposition of
      apolipoprotein(a) in the aorta, compared with the lysine binding site mutant
      strain and to nontransgenic littermates. The results demonstrate the key role of
      this lysine binding site in the pathogenic activity of apolipoprotein(a) in a
      murine model system.

PMID- 9239404
TI  - A role for TGFbeta1 in langerhans cell biology. Further characterization of the
      epidermal Langerhans cell defect in TGFbeta1 null mice.
AB  - Previous studies of TGFbeta1 null (-/-) mice indicated that the epidermis was
      devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to
      the inflammation that is the dominant feature of the -/- phenotype (Borkowski,
      T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422).
      Herein, we demonstrate that dendritic cells could be expanded from the bone
      marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave
      rise to LC after transfer into lethally irradiated recipients. Thus, the LC
      defect in TGFbeta1 null mice does not result from an absolute deficiency in bone
      marrow precursors, and paracrine TGFbeta1 production is sufficient for LC
      development. Several approaches were used to assess the suitability of -/- skin
      for LC localization. A survey revealed that although a number of cytokine mRNAs
      were expressed de novo, mRNAs encoding proinflammatory cytokines known to
      mobilize LC from epidermis (IL-1 and TNFalpha) were not strikingly
      overrepresented in -/- skin. In addition, bone marrow-derived LC populated full
      thickness TGFbeta1 null skin after engraftment onto BALB/c nu/nu recipients.
      Finally, the skin of transgenic mice expressing a truncated loricrin promoter
      driven dominant-negative TGFbeta type II receptor contained normal numbers of LC.
      Because TGFbeta1 signaling in these mice is disrupted only in keratinocytes and
      the keratinocyte hyperproliferative component of the TGFbeta1 -/- phenotype is
      reproduced, these results strongly suggest that the LC defect in TGFbeta1 null
      mice is not due to an epidermal abnormality but reflects a requirement of murine
      LC (or their precursors) for TGFbeta1.

PMID- 9239403
TI  - Alpha toxin from Clostridium perfringens induces proinflammatory changes in
      endothelial cells.
AB  - Alpha toxin from Clostridium perfringens type A, a phospholipase C, has been
      implicated in many of the localized and systemic features of gas gangrene. We
      demonstrated that human endothelial cells synthesize two vasoactive lipids,
      platelet-activating factor (PAF) and prostacyclin, in response to alpha toxin
      treatment. The stimulated synthesis of PAF required the enzymatic activity of the
      toxin and subsequent protein kinase C activation. Alpha toxin-treated endothelial
      cells accumulated the products of the phospholipase C reaction, diacylglycerol
      and ceramide, and exhibited a decrease in the enzymatic precursors
      phosphatidylcholine and sphingomyelin. Furthermore, the temporal accumulation of
      PAF depended on the concentration of the toxin in the overlying medium and was
      blocked in the presence of a neutralizing antibody. The cultured endothelial
      cells also exhibited enhanced neutrophil adhesion in response to alpha toxin
      which was mediated through the PAF receptor and P-selectin. P-selectin expression
      by endothelial cells and extravascular neutrophil accumulation were also observed
      in tissue sections from alpha toxin-injected Sprague-Dawley rats. These
      endothelial cell-mediated processes are important in maintaining vascular
      homeostasis and, when activated in a dysregulated manner by C. perfringens alpha
      toxin, may contribute to localized and systemic manifestations of gas gangrene
      including enhanced vascular permeability, localized neutrophil accumulation, and
      myocardial dysfunction.

PMID- 9239405
TI  - Activation of extracellular signal-regulated kinase in proliferative
      glomerulonephritis in rats.
AB  - Multiple extracellular mitogens are involved in the pathogenesis of proliferative
      forms of glomerulonephritis (GN). In vitro studies demonstrate the pivotal role
      of extracellular signal-regulated kinase (ERK) in the regulation of cellular
      proliferation in response to extracellular mitogens. In this study, we examined
      whether this kinase, as a convergence point of mitogenic stimuli, is activated in
      proliferative GN in vivo. Two different proliferative forms of anti-glomerular
      basal membrane (GBM) GN in rats were induced and whole cortical tissue as well as
      isolated glomeruli examined using kinase activity assays and Western blot
      analysis. Administration of rabbit anti-rat GBM serum to rats, preimmunized with
      rabbit IgG, induced an accelerated crescentic anti-GBM GN. A significant increase
      in cortical, and more dramatically glomerular ERK activity was detected at 1, 3,
      and 7 d after induction of GN. Immunization of Wistar-Kyoto rats with bovine GBM
      also induced a crescentic anti-GBM GN with an increase of renal cortical ERK
      activity after 4, 6, and 8 wk. ERK is phosphorylated and activated by the MAP
      kinase/ERK kinase (MEK). We detected a significant increase in the expression of
      glomerular MEK in the accelerated form of anti-GBM GN, providing a possible
      mechanism of long-term activation of ERK in this disease model. In contrast to
      ERK, activation of stress-activated protein kinase was only detectable at early
      stages of proliferative GN, indicating these related kinases to serve distinct
      roles in the pathogenesis of GN. Our observations point to ERK as a putative
      mediator of the proliferative response to immune injury in GN and suggest that
      upregulation of MEK is involved in the long-term regulation of ERK in vivo.

PMID- 9239406
TI  - Hemodynamic forces induce the expression of heme oxygenase in cultured vascular
      smooth muscle cells.
AB  - Both nitric oxide (NO) and carbon monoxide (CO) are vessel wall-derived messenger
      molecules that cause platelet inhibition and vasodilation by activating guanylyl
      cyclase in target cells. Since vascular smooth muscle cells (SMCs) are exposed to
      shear and tensile stresses, this study examined the effects of these hemodynamic
      forces on the enzymes that generate NO and CO in SMCs. Monolayers of cultured rat
      aortic SMCs were subjected to shear stress using a modified cone and plate
      viscometer, or cyclic elongational stretch using a compliant silastic culture
      membrane. Shear stress stimulated time-dependent increases in mRNA and protein
      for inducible heme oxygenase-1 (HO-1), the enzyme which forms CO as a byproduct
      of heme degradation. The threshold level of shear necessary to induce HO-1
      expression was between 5 and 10 dynes/cm2. In contrast, shear stress did not
      stimulate inducible NO synthase (iNOS) expression. Cyclic stretch also induced
      the expression of HO-1 but not of iNOS mRNA. Exposure of vascular SMCs to shear
      stress stimulated the production and release of CO as demonstrated by the CO
      dependent increase in intracellular cGMP levels in coincubated platelets. In
      addition, ADP-stimulated aggregation was inhibited in platelets exposed to
      sheared SMCs but not in platelets exposed to untreated control SMCs. Treatment of
      sheared SMCs with the HO-1 inhibitor, tin protoporphyrin-IX, blocked the
      antiaggregatory effect of the cells, whereas the iNOS inhibitor, methyl-
      arginine, had no effect. These results indicate that hemodynamic forces induce HO
      1 gene expression and CO production in vascular SMCs, and that SMC-derived CO
      inhibits platelet aggregation. Thus, CO is a novel endogenous vessel wall-derived
      messenger molecule that may be selectively induced by hemodynamic forces to
      inhibit platelet reactivity and preserve blood fluidity at sites of vascular
      injury.

PMID- 9239407
TI  - Cholecystokinin A and B receptors are differentially expressed in normal pancreas
      and pancreatic adenocarcinoma.
AB  - Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While
      human CCK-A and -B receptors have been fully characterized, their relative roles
      in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and 
      B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human
      extrapancreatic tissues and malignancies was examined, using reverse
      transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated
      from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58
      extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific
      for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in
      all tissues arising from pancreas and in most extrapancreatic tissues and tumors.
      In contrast, CCK-A receptors exhibited a more selective pattern of expression in
      gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A
      receptors were expressed selectively in all pancreatic adenocarcinomas, but not
      in any normal pancreas specimens. In situ hybridization, using receptor-specific
      riboprobes, localized CCK-A receptor expression to ductal cells, the presumed
      origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed
      no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic
      adenocarcinomas. Because of its selective expression, the CCK-A receptor may
      serve as selective biomarker for pancreatic adenocarcinoma.

PMID- 9239408
TI  - Microglial production of TNF-alpha is induced by activated T lymphocytes.
      Involvement of VLA-4 and inhibition by interferonbeta-1b.
AB  - TNF-alpha is a proinflammatory cytokine involved in many inflammatory conditions
      such as Crohn's disease, rheumatoid arthritis, cachexia, AIDS, and multiple
      sclerosis (MS). TNF-alpha is produced mainly by cells of the macrophage lineage,
      which includes microglia in the central nervous system. Here, we describe a
      mechanism through which TNF-alpha is generated by microglia. We show that
      activated human T lymphocytes induce the microglial production of TNF-alpha, and
      that is attenuated by a functional blocking antibody to CD49d, the alpha chain of
      the VLA-4 integrin on T cells. We also report that interferonbeta-1b (IFNbeta
      1b), a drug that alleviates symptoms in MS, downregulates the expression of CD49d
      and reduces TNF-alpha production, mechanisms which can help account for its
      efficacy in MS.

PMID- 9239409
TI  - Neurological dysfunction and hyperactive behavior associated with
      antiphospholipid antibodies. A mouse model.
AB  - Antiphospholipid antibodies (aPL) have been associated with various neurological
      manifestations, but the underlying mechanism has not been elucidated. We assessed
      mice with induced experimental antiphospholipid syndrome (APS) for neurological
      and behavioral changes. After immunization with monoclonal human anticardiolipin
      antibody (H-3), female BALB/c mice developed elevated levels of circulating anti
      negatively charged phospholipids (aPL), anti-beta2-glycoprotein I (abeta2GPI),
      and anti-endothelial cell antibodies (AECA), along with clinical manifestations
      of APS like thrombocytopenia and fetus resorption. APS mice were impaired
      neurologically and performed several reflexes less accurately compared to the
      controls, including placing reflex (P < 0.05), postural reflex (P < 0.05), and
      grip test (P = 0.05). The APS mice also exhibited hyperactive behavior in an open
      field, which tests spatial behavior (P < 0.03), and displayed impaired motor
      coordination on a rotating bar. aPL in combination with abeta2GPI and AECA is
      probably involved in the neurological and behavioral defects shown in mice with
      experimental APS.

PMID- 9239410
TI  - Genetic correction of dystrophin deficiency and skeletal muscle remodeling in
      adult MDX mouse via transplantation of retroviral producer cells.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked, lethal disease caused by
      mutations of the dystrophin gene. No effective therapy is available, but
      dystrophin gene transfer to skeletal muscle has been proposed as a treatment for
      DMD. We have developed a strategy for efficient in vivo gene transfer of
      dystrophin cDNA into regenerating skeletal muscle. Retroviral producer cells,
      which release a vector carrying the therapeutically active dystrophin minigene,
      were mitotically inactivated and transplanted in adult nude/mdx mice.
      Transplantation of 3 x 10(6) producer cells in a single site of the tibialis
      anterior muscle resulted in the transduction of between 5.5 and 18% total muscle
      fibers. The same procedure proved also feasible in immunocompetent mdx mice under
      short-term pharmacological immunosuppression. Minidystrophin expression was
      stable for up to 6 mo and led to alpha-sarcoglycan reexpression. Muscle stem
      cells could be transduced in vivo using this procedure. Transduced dystrophic
      skeletal muscle showed evidence of active remodeling reminiscent of the genetic
      normalization process which takes place in female DMD carriers. Overall, these
      results demonstrate that retroviral-mediated dystrophin gene transfer via
      transplantation of producer cells is a valid approach towards the long-term goal
      of gene therapy of DMD.

PMID- 9239411
TI  - Stimulation of activin A expression in rat aortic smooth muscle cells by thrombin
      and angiotensin II correlates with neointimal formation in vivo.
AB  - Vasoactive GTP-binding protein-coupled receptor agonists (e.g., angiotensin II
      [AII] and alpha-thrombin) stimulate the production of mitogenic factors from
      vascular smooth muscle cells. In experiments to identify mitogens secreted from
      AII- or alpha-thrombin-stimulated rat aortic smooth muscle (RASM) cells,
      neutralizing antibodies directed against several growth factors (e.g., PDGF and
      basic fibroblast growth factor [basic FGF]) failed to inhibit the mitogenic
      activity of conditioned media samples derived from the cells. In this report, we
      found that polyclonal neutralizing antibodies directed against purified human
      placental basic FGF reduced the mitogenic activity of AII-stimulated RASM cell
      conditioned media and in immunoblot experiments identified a 26-kD protein (14 kD
      under reducing conditions) that was distinct from basic FGF. After purification
      from RASM cell-conditioned medium, amino acid sequence analysis identified the
      protein as activin A, a member of the TGF-beta superfamily. Increased activin A
      expression was observed after treatment of the RASM cells with AII, alpha
      thrombin, and the protein kinase C agonist PMA. In contrast, PDGF-BB or serum
      caused only a minor induction of this protein. Although activin A alone only
      weakly stimulated RASM cell DNA synthesis, it demonstrated a potent comitogenic
      effect in combination with either EGF or heparin-binding EGF-like growth factor
      in the RASM cells, increasing DNA synthesis by up to fourfold. Furthermore, in a
      rat carotid injury model, activin A mRNA was upregulated within 6 h after injury
      followed by increases in immunoreactive protein detected in the expanding
      neointima 7 and 14 d later. Taken together, these results indicate that activin A
      is a vascular smooth muscle cell-derived factor induced by vasoactive agonists
      that may, either alone or in combination with other vascular derived growth
      factors, have a role in neointimal formation after arterial injury.

PMID- 9239413
TI  - Genetic bias in immune responses to a cassette shared by different microorganisms
      in patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease associated with HLA-DRbeta1
      alleles which contain the QKRAA amino acid sequence in their third hypervariable
      region(s). The QKRAA sequence is also expressed by several human pathogens. We
      have shown previously that an Escherichia coli peptide encompassing QKRAA is a
      target of immune responses in RA patients. Here we address two questions: first,
      whether QKRAA may function as an "immunological cassette" with similar, RA
      associated, immunogenic properties when expressed by other common human
      pathogens; and second, what is the influence of genetic background in the
      generation of these responses. We find that early RA patients have enhanced
      humoral and cellular immune responses to Epstein-Barr virus and Brucella ovis and
      Lactobacillus lactis antigens which contain the QKRAA sequence. These results
      suggest that the QKRAA sequence is an antigenic epitope on several different
      microbial proteins, and that RA patients recognize the immunological cassette on
      different backgrounds. ANOVA of immune responses to "shared epitope" antigens in
      monozygotic twin couples shows that, despite significantly elevated responses in
      affected individuals, a similarity between pairs is retained, thus suggesting a
      role played either by hereditary or shared environmental factors in the genesis
      or maintenance of these responses.

PMID- 9239412
TI  - Lipoprotein lipase regulates Fc receptor-mediated phagocytosis by macrophages
      maintained in glucose-deficient medium.
AB  - During periods of intense activity such as phagocytosis, macrophages are thought
      to derive most of their energy from glucose metabolism under both aerobic and
      anaerobic conditions. To determine whether fatty acids released from lipoproteins
      by macrophage lipoprotein lipase (LPL) could substitute for glucose as a source
      of energy for phagocytosis, we cultured peritoneal macrophages from normal and
      LPL knockout (LPL-KO) mice that had been rescued from neonatal demise by
      expression of human LPL via the muscle creatine kinase promoter. Normal and LPL
      KO macrophages were cultured in medium containing normal (5 mM) or low (1 mM)
      glucose, and were tested for their capacity to phagocytose IgG-opsonized sheep
      erythrocytes. LPL-KO macrophages maintained in 1 and 5 mM glucose phagocytosed 67
      and 79% fewer IgG-opsonized erythrocytes, respectively, than macrophages from
      normal mice. Addition of VLDL to LPL-expressing macrophages maintained in 1 mM
      glucose enhanced the macrophages' phagocytosis of IgG-opsonized erythrocytes, but
      did not stimulate phagocytosis by LPL-KO macrophages. Inhibition of secreted LPL
      with a monoclonal anti-LPL antibody or with tetrahydrolipstatin blocked the
      ability of VLDL to enhance phagocytosis by LPL-expressing macrophages maintained
      in 1 mM glucose. Addition of oleic acid significantly enhanced phagocytosis by
      both LPL-expressing and LPL-KO macrophages maintained in 1 mM glucose. Moreover,
      oleic acid stimulated phagocytosis in cells cultured in non-glucose-containing
      medium, and increased the intracellular stores of creatine phosphate. Inhibition
      of oxidative phosphorylation, but not of glycolysis, blocked the capacity of
      oleic acid to stimulate phagocytosis. Receptor-mediated endocytosis of acetyl LDL
      by macrophages from LPL-expressing and LPL-KO mice was similar whether the cells
      were maintained in 5 or 1 mM glucose, and was not augmented by VLDL. We postulate
      that fatty acids derived from macrophage LPL-catalyzed hydrolysis of
      triglycerides and phospholipids provide energy for macrophages in areas that have
      limited amounts of ambient glucose, and during periods of intense metabolic
      activity.

PMID- 9239414
TI  - Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases
      nitric oxide production in cirrhotic rats with portal hypertension and ascites.
AB  - Tumor necrosis factor-alpha (TNF) causes vasodilatation and a hyperdynamic state
      by activating nitric oxide (NO) synthesis. Tyrphostins, specific inhibitors of
      protein tyrosine kinase (PTK), block the signaling events induced by TNF and NO
      production. A hyperdynamic circulatory syndrome (HCS) is often observed in portal
      hypertension (PHT). TNF and NO seem to mediate these hemodynamic changes. The aim
      of this work was to study the effect of PTK inhibition on the systemic and portal
      hemodynamics, TNF and NO production, in cirrhotic rats with portal hypertension.
      Rats with liver cirrhosis induced by chronic inhalation of carbon tetrachloride
      were used. Animals were treated daily with tyrphostin AG 126 (alpha-cyano-(3
      hydroxy-4-nitro) cinnamonitrile) or placebo for 5 d. Mean arterial pressure
      (MAP), heart rate (HR), and portal pressure (PP) were measured by indwelling
      catheters. Cardiac output (CI) and stroke volume (SV) were estimated by
      thermodilution, systemic vascular resistance (SVR) was calculated (MAP/CI), and
      portal systemic shunting (PSS) was quantitated using radioactive microspheres.
      Serum and mesenteric lymph node (MLN) TNF levels were measured using an
      immunoassay kit, and serum NOx was determined photometrically by its oxidation
      products. The AG 126-treated group showed a statistically significant increase in
      MAP and SVR, and decreases in CI, SV, MLN TNF, and serum NO oxidation products
      nitrite and nitrate (NOx) in comparison with the placebo-treated rats. No
      significant differences were noticed in HR, PP, PSS, or serum TNF. Significant
      correlations were observed between MAP and NOx, MAP and MLN TNF, PSS and NOx, and
      serum TNF and serum NOx. The HCS observed in PHT seems to be mediated, at least
      in part, by TNF and NO by the activation of PTKs and their signaling pathways.
      PTK activity inhibition ameliorates the hyperdynamic abnormalities that
      characterize animals with cirrhosis and PHT.

PMID- 9239415
TI  - Muscle-specific transgenic complementation of GLUT4-deficient mice. Effects on
      glucose but not lipid metabolism.
AB  - We have taken the approach of introducing the muscle-specific myosin light chain
      (MLC)-GLUT4 transgene into the GLUT4-null background to assess the relative role
      of muscle and adipose tissue GLUT4 in the etiology of the GLUT4-null phenotype.
      The resulting MLC-GLUT4-null mice express GLUT4 predominantly in the fast-twitch
      extensor digitorum longus (EDL) muscle. GLUT4 is nearly absent in female white
      adipose tissue (WAT) and slow-twitch soleus muscle of both sexes of MLC-GLUT4
      null mice. GLUT4 content in male MLC-GLUT4-null WAT is 20% of that in control
      mice. In transgenically complemented EDL muscle, 2-deoxyglucose (2-DOG) uptake
      was restored to normal (male) or above normal (female) levels. In contrast, 2-DOG
      uptake in slow-twitch soleus muscle of MLC-GLUT4-null mice was not normalized.
      With the normalization of glucose uptake in fast-twitch skeletal muscle, whole
      body insulin action was restored in MLC-GLUT4-null mice, as shown by the results
      of the insulin tolerance test. These results demonstrate that skeletal muscle
      GLUT4 is a major regulator of skeletal muscle and whole body glucose metabolism.
      Despite normal skeletal muscle glucose uptake and insulin action, the MLC-GLUT4
      null mice exhibited decreased adipose tissue deposits, adipocyte size, and fed
      plasma FFA levels that are characteristic of GLUT4-null mice. Together these
      results indicate that the defects in skeletal muscle and whole body glucose
      metabolism and adipose tissue in GLUT4-null mice arise independently.

PMID- 9239417
TI  - Barrier effects of hyperosmolar signaling in microvascular endothelium of rat
      lung.
AB  - We determined the effects of hyperosmolarity on lung microvascular barrier
      properties by means of the split-drop technique in single venular capillaries of
      the isolated, blood-perfused rat lung. Using isosmolar and hyperosmolar test
      solutions (colloid osmotic pressure = 21 cm H2O), we quantified transcapillary
      flux at a fixed absorptive capillary pressure, and the capillary hydraulic
      conductivity (Lp). Loss of barrier function was indicated in flux reversal from
      isosmolar absorption to hyperosmolar filtration (P < 0. 01), and by
      hyperosmolarity-induced Lp increase (P < 0.01). Barrier recovery after a 1-min
      hyperosmolar exposure was delayed > 25 min. The flux reversal was blocked by the
      tyrosine kinase inhibitors genistein and MDC (P < 0.01). Genistein also inhibited
      the Lp increase (P < 0.01). Immunoblots of hyperosmolarity-exposed, cultured rat
      lung microvascular endothelial cells (RLMEC) and of endothelial cells freshly
      harvested from lungs given hyperosmolar infusions indicated a genistein
      inhibitable enhancement of protein tyrosine phosphorylation. Immunoprecipitation
      studies indicated tyrosine phosphorylation of the mitogen activated protein
      kinases (MAPK) ERK1 and ERK2 and the adaptor protein Shc in lysates of RLMEC
      exposed to hyperosmolar conditions. We conclude that in lung venular capillaries
      hyperosmolarity deteriorates barrier properties, possibly by inducing tyrosine
      phosphorylation of endothelial proteins.

PMID- 9239416
TI  - Improvement in endothelial function by angiotensin converting enzyme inhibition
      in insulin-dependent diabetes mellitus.
AB  - We postulated that nitric oxide (NO)-mediated endothelial function would be
      improved by acute and short-term treatment with an angiotensin converting enzyme
      (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial
      function is depressed. Nine type I diabetic patients and eight healthy subjects
      underwent forearm blood flow measurement using strain gauge plethysmography
      during intraarterial infusion of incremental doses of endothelium-dependent
      (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP])
      vasodilators. Pretreatment ACh responses were depressed in diabetic patients
      relative to the normal subjects (P < 0.05). No difference between the groups was
      evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat)
      enhanced ACh responses in the diabetic patients (P < 0.005), with a further
      improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when
      ACh responses were normalized. ACE inhibition did not affect SNP responses. We
      conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO
      mediated endothelial function in type I diabetic patients, with further
      improvement evident after 4 wk of enalapril therapy.

PMID- 9239418
TI  - The inhibition of vascular smooth muscle cell migration by peptide and antibody
      antagonists of the alphavbeta3 integrin complex is reversed by activated
      calcium/calmodulin- dependent protein kinase II.
AB  - The migration of vascular smooth muscle cells (VSMCs) is thought to play a key
      role in the pathogenesis of many vascular diseases and is regulated by soluble
      growth factors/ chemoattractants as well as interactions with the extracellular
      matrix. We have studied the effects of antibodies to rat beta3 and human
      alphavbeta3 integrins on the migration of VSMCs. Both integrin antibodies as well
      as cyclic RGD peptides that bind to the vitronectin receptors alphavbeta3 and
      alphavbeta5 significantly inhibited PDGF-directed migration. This resulted in a
      reduction in the accumulation of inositol (1,4,5) trisphosphate and the
      activation of calcium/calmodulin-dependent protein kinase II (CamKII), an
      important regulatory event in VSMC migration identified previously. PDGF-directed
      VSMC migration in the presence of the anti-integrin antibodies and cyclic RGD
      peptides was restored when intracellular CamKII activity was elevated by either
      raising intracellular calcium levels with the ionophore, ionomycin, or infecting
      with a replication-defective recombinant adenovirus expressing a constitutively
      activated CamKII cDNA (AdCMV.CKIID3). Rescue of rat VSMCs was also observed in
      stably transfected cell lines expressing constitutively activated but not wild
      type CamKII. These observations identify a key intermediate in the regulation of
      VSMC migration by outside-in signaling from the integrin alphavbeta3.

PMID- 9239419
TI  - Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the
      development of the fetal epidermal permeability barrier.
AB  - Members of the superfamily of nuclear hormone receptors which are obligate
      heterodimeric partners of the retinoid X receptor may be important in epidermal
      development. Here, we examined the effects of activators of the receptors for
      vitamin D3 and retinoids, and of the peroxisome proliferator activated receptors
      (PPARs) and the farnesoid X-activated receptor (FXR), on the development of the
      fetal epidermal barrier in vitro. Skin explants from gestational day 17 rats
      (term is 22 d) are unstratified and lack a stratum corneum (SC). After incubation
      in hormone-free media for 3-4 d, a multilayered SC replete with mature lamellar
      membranes in the interstices and a functionally competent barrier appear. 9-cis
      or all-trans retinoic acid, 1,25 dihydroxyvitamin D3, or the PPARgamma ligands
      prostaglandin J2 or troglitazone did not affect the development of barrier
      function or epidermal morphology. In contrast, activators of the PPARalpha, oleic
      acid, linoleic acid, and clofibrate, accelerated epidermal development, resulting
      in mature lamellar membranes, a multilayered SC, and a competent barrier after 2
      d of incubation. The FXR activators, all-trans farnesol and juvenile hormone III,
      also accelerated epidermal barrier development. Activities of beta
      glucocerebrosidase and steroid sulfatase, enzymes previously linked to barrier
      maturation, also increased after treatment with PPARalpha and FXR activators. In
      contrast, isoprenoids, such as nerolidol, cis-farnesol, or geranylgeraniol, or
      metabolites in the cholesterol pathway, such as mevalonate, squalene, or 25
      hydroxycholesterol, did not alter barrier development. Finally, additive effects
      were observed in explants incubated with clofibrate and farnesol together in
      suboptimal concentrations which alone did not affect barrier development. These
      data indicate a putative physiologic role for PPARalpha and FXR in epidermal
      barrier development.

PMID- 9239420
TI  - Cytosolic-free calcium increases to greater than 100 micromolar in ATP-depleted
      proximal tubules.
AB  - Previous studies have shown that cytosolic-free Ca2+ (Caf) increases to at least
      low micromolar concentrations during ATP depletion of isolated kidney proximal
      tubules. However, peak levels could not be determined precisely with the Ca2+
      sensitive fluorophore, fura-2, because of its high affinity for Ca2+. Now, we
      have used two low affinity Ca2+ fluorophores, mag-fura-2 (furaptra) and fura-2FF,
      to quantitate the full magnitude of Caf increase. Between 30 and 60 min after
      treatment with antimycin to deplete ATP in the presence of glycine to prevent
      lytic plasma membrane damage, Caf measured with mag-fura-2 exceeded 10 microM in
      91% of tubules studied and 68% had increases to greater than 100 microM. Caf
      increases of similar magnitude that were dependent on influx of medium Ca2+ were
      also seen using the new low Ca2+ affinity, Mg2+-insensitive, fluorophore fura-2FF
      in tubules depleted of ATP by hypoxia, and these increases were reversed by
      reoxygenation. Total cell Ca2+ levels in antimycin-treated or hypoxic tubules did
      not change, suggesting that mitochondria were not buffering the increased Caf
      during ATP depletion. Considered in the context of the high degree of structural
      preservation of glycine-treated tubule cells during ATP depletion and the
      commonly assumed Ca2+ requirements for phospholipid hydrolysis, actin
      disassembly, and Ca2+-mediated structural damage, the remarkable elevations of
      Caf demonstrated here suggest an unexpected resistance to the deleterious effects
      of increased Caf during energy deprivation in the presence of glycine.

PMID- 9239421
TI  - Endothelial dysfunction in a rat model of endotoxic shock. Importance of the
      activation of poly (ADP-ribose) synthetase by peroxynitrite.
AB  - DNA single strand breakage and activation of the nuclear enzyme poly (ADP-ribose)
      synthetase (PARS) contribute to peroxynitrite-induced cellular injury. We
      investigated the role of PARS activation in the pathogenesis of endothelial
      dysfunction. In human umbilical vein endothelial cells (HUVEC), DNA strand
      breakage (alkaline unwinding assay), PARS activation (incorporation or
      radiolabeled NAD+ into proteins), mitochondrial respiration [conversion of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to formazan] and apoptotic
      index (cytoplasmatic release of histones) were measured. Endotoxin shock was
      induced in rats by bacterial lipopolysaccharide. Vascular reactivity of thoracic
      aortic rings were measured in organ chambers. In HUVEC, peroxynitrite caused a
      dose-dependent suppression of mitochondrial respiration, induced DNA strand
      breakage and caused an activation of PARS. Pharmacological inhibition of PARS
      reduced the acute and delayed suppression of mitochondrial respiration when cells
      were exposed to intermediate, but not high doses of peroxynitrite. Similarly,
      protection against the intermediate, but not high doses of peroxynitrite was seen
      in fibroblasts from the PARS-/- mice, when compared to wild-type controls. These
      data suggest that PARS plays a role in peroxynitrite-induced cytotoxicity, but at
      very high levels of oxidant exposure, PARS-independent cytotoxic mechanisms
      become predominant. Peroxynitrite-induced apoptosis was not affected by PARS
      inhibition. Vascular rings exposed to peroxynitrite and rings taken from rats
      subjected to endotoxic shock exhibited reduced endothelium-dependent relaxant
      responses in response to acetylcholine. The development of this endothelial
      dysfunction was ameliorated by the PARS inhibitor 3-aminobenzamide. Activation of
      PARS by peroxynitrite, therefore, may be involved in the development of
      endothelial dysfunction in endotoxemia.

PMID- 9239422
TI  - E2 transacylase-deficient (type II) maple syrup urine disease. Aberrant splicing
      of E2 mRNA caused by internal intronic deletions and association with thiamine
      responsive phenotype.
AB  - Maple syrup urine disease (MSUD) or branched-chain alpha-ketoaciduria is an
      autosomally inherited disorder in the catabolism of branched-chain amino acids
      leucine, isoleucine, and valine. The disease is characterized by severe
      ketoacidosis, mental retardation, and neurological impairments. MSUD can be
      classified into genetic subtypes according to the genes of the branched-chain
      alpha-ketoacid dehydrogenase (BCKD) complex which are affected in patients. We
      describe here four intronic deletions and an intronic nucleotide substitution in
      the E2 transacylase gene of type II MSUD, in which the E2 subunit of the BCKD
      complex is deficient. These new E2 mutations comprise an internal 3.2-kb deletion
      in intron 4 (causing a 17-bp insertion in mRNA), an internal 12-bp (ttaccttgttac)
      deletion in intron 4 (creating a 10-bp insertion), a 10-bp (catttctaG) deletion
      in intron 10/ exon 11 junction (leading to a 21-bp deletion), a 2-bp deletion in
      the exon 5/intron 5 junction (ATgt--> A-t) (resulting in the skipping of exon 5),
      and a G to A transition at nucleotide -7 of intron 9 (causing a 6-bp insertion).
      These intronic mutations were initially detected by secondary alterations in the
      mutant E2 mRNA, as a result of aberrant splicing. The 3.2-kb deletion in intron 4
      was determined by the amplification of the entire intron from both a normal
      subject (11.2 kb) and a homozygous patient (8 kb) by long PCR, followed by
      subcloning and sequencing of regions flanking the deletion. Similar methods were
      used to identify and characterize the other intronic alterations. Our results
      depict heretofore undescribed splicing errors caused by the deletion of internal
      intronic segments, and provide an approach for detecting this class of novel and
      rare human mutation. The association of the thiamine-responsive phenotype with a
      subset of the type II MSUD patients studied is also discussed.

PMID- 9239424
TI  - Cardiac disease in chronic uremia: epidemiology.
AB  - Cardiac abnormalities develop during chronic renal failure. The prevalence of
      ischemic heart disease, cardiac failure, and left ventricular disorders is high
      among patients initiating end-stage renal disease (ESRD) therapy, and appears to
      be getting higher. Age, gender, race, diabetes, and possibly geographic location
      are predictive of the presence of several cardiac conditions. Cardiac morbidity
      after the initiation of ESRD therapy is high, and cardiac causes are the most
      common reported cause of death. Cardiac abnormalities present on starting
      dialysis contribute to this morbidity and mortality. In epidemiological studies,
      higher cardiac death rates have also been associated with dialysis rather than
      transplantation as mode of ESRD therapy, peritoneal rather than hemodialysis,
      lower dose of dialysis, and unmodified cellulose rather than modified
      cellulose/synthetic hemodialysis membranes.

PMID- 9239423
TI  - Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma
      hydroxybutyrate in normal young Men.
AB  - The aim of this study was to investigate, in normal young men, whether gamma
      hydroxybutyrate (GHB), a reliable stimulant of slow-wave (SW) sleep in normal
      subjects, would simultaneously enhance sleep related growth hormone (GH)
      secretion. Eight healthy young men participated each in four experiments
      involving bedtime oral administration of placebo, 2.5, 3.0, and 3.5 g of GHB.
      Polygraphic sleep recordings were performed every night, and blood samples were
      obtained at 15-min intervals from 2000 to 0800. GHB effects were mainly observed
      during the first 2 h after sleep onset. There was a doubling of GH secretion,
      resulting from an increase of the amplitude and the duration of the first GH
      pulse after sleep onset. This stimulation of GH secretion was significantly
      correlated to a simultaneous increase in the amount of sleep stage IV. Abrupt but
      transient elevations of prolactin and cortisol were also observed, but did not
      appear to be associated with the concomitant stimulation of SW sleep. Thyrotropin
      and melatonin profiles were not altered by GHB administration. These data suggest
      that pharmacological agents that reliably stimulate SW sleep, such as GHB, may
      represent a novel class of powerful GH secretagogues.

PMID- 9239425
TI  - Cardiac disease in chronic uremia: pathogenesis.
AB  - Cardiomyopathy in chronic uremia results from pressure and volume overload. The
      former causes concentric left ventricular [LV] hypertrophy, results from
      hypertension and aortic stenosis, and is also associated with diabetes mellitus
      and anemia. Volume overload causes LV dilatation, results from arteriovenous
      shunting, salt and water overload, and anemia, and is also associated with
      ischemic heart disease, hypertension, and hypoalbuminemia. Decreased major
      arterial compliance and an early return of arterial wave reflections are also
      associated with the extent of LV hypertrophy. Cardiomyopathy predisposes to
      diastolic and systolic dysfunction. The latter results from myocyte death, and
      predisposing factors include ischemic heart disease and the uremic environment.
      Ischemic heart disease may be atherosclerotic or nonatherosclerotic in origin.
      Multiple factors contribute to the vascular pathology of chronic uremia,
      including injury to the vessel wall, dyslipidemia, prothrombotic factors,
      increased oxidant stress, and hyperhomocysteinemia. Ischemic risk factors include
      hypertension, LV hypertrophy, hypoalbuminemia, and perhaps hyperparathyroidism.
      The clinical consequences of cardiomyopathy include heart failure, ischemic heart
      disease, dialysis hypotension, and arrhythmias. The adverse impact of ischemic
      heart disease is probably mediated through the development of cardiac failure.

PMID- 9239426
TI  - Cardiac disease in chronic uremia: pathophysiology.
AB  - In chronic uremia, apart from frequent coronary lesions, further abnormalities of
      the heart recently reported include (1) left ventricular hypertrophy, not
      completely explained by hypertension, (2) interstitial myocardial fibrosis, for
      which parathyroid hormone is a permissive factor, (3) reduced myocardial
      perfusion reserve, secondary to functional and structural changes of
      intramyocardial arteries and to reduced capillary density, (4) abnormalities of
      myocardial metabolism, which act in concert with restriction of blood flow by
      microvascular abnormalities to reduce ischemic tolerance. Such metabolic
      abnormalities include diminished responsiveness to beta-adrenergic stimulation,
      abnormal control of intracellular calcium concentration, impaired maintenance of
      energy-rich nucleotide concentrations under conditions of ischemia, impaired
      insulin-mediated glucose uptake, and abnormalities of myocardial oxidative
      metabolism.

PMID- 9239427
TI  - Cardiac disease in chronic uremia: investigation.
AB  - Cardiovascular disease continues to be the leading cause of death in the end
      stage renal disease (ESRD) population, accounting for nearly half of the deaths
      among the dialysis population. The purpose of this article is to review the
      clinical screening tools available to the attending nephrologist and consulting
      cardiologist to detect both symptomatic and asymptomatic cardiovascular disease
      in ESRD patients. The author presents a detailed overview of (1) assessment of
      left ventricular (LV) function in the hemodialysis population and (2) noninvasive
      cardiovascular screening in patients before anticipated renal transplantation.
      Specific guidelines are offered for the pretransplantation evaluation of cardiac
      disease based on the patient's cardiovascular risk factors, symptomatology, and
      stress testing with either thallium or dobutamine echocardiography. Recent
      studies of cardiovascular screening in selected hemodialysis populations may not
      be extrapolated to the general ESRD population pending further investigation.
      Crucial questions relating to the utility of cardiovascular screening and
      intervention in the general ESRD population remain and deserve further study.

PMID- 9239428
TI  - Cardiac disease in chronic uremia: clinical outcome and risk factors.
AB  - Cardiac disease is common and is the major killer in end-stage renal disease
      (ESRD). Cardiac failure is a highly malignant condition in ESRD patients. Cardiac
      failure mediates most of the adverse prognostic impact of ischemic heart disease.
      Left ventricular (LV) abnormalities are already present at initiation of dialysis
      therapy in approximately 80% of patients. These abnormalities (ie, systolic
      dysfunction in approximately 15%, LV dilatation with preserved systolic function
      in 30%, concentric LV hypertrophy [LVH] in 40%) independently predict ischemic
      heart disease and cardiac failure, and are the largest baseline predictor of
      mortality after 2 years on dialysis therapy. The associations between classical
      risk factors (eg, hyperlipidemia, smoking, hypertension) and cardiac outcomes in
      ESRD are inconsistent. "Uremic" risk factors represent a nascent, but potentially
      important field. In our prospective 10-year study of 433 patients starting renal
      replacement therapy, we identified the following as major independent risk
      factors for cardiac disease: (1) hypertension (concentric LVH, LV dilatation,
      ischemic heart disease, cardiac failure, inverse relationship with mortality);
      (2) anemia (LV dilatation, cardiac failure, death); and (3) hypoalbuminemia
      (ischemic heart disease, cardiac failure, death). Transplantation dramatically
      improved LV abnormalities, suggesting that a uremic environment is cardiotoxic.
      Multiple risk factors act in concert to produce cardiac disease in ESRD; many of
      these are avoidable, suggesting that the enormous burden of disease can be
      reduced considerably.

PMID- 9239429
TI  - Cardiac disease in chronic uremia: management.
AB  - Heart disease is a common cause of morbidity in end-stage renal disease (ESRD)
      patients. The management of heart disease in these patients requires a
      multidimensional approach to the management of heart failure, coronary disease,
      and arrhythmias, and to risk factors such as hypertension, anemia, secondary
      hyperparathyroidism, and electrolyte/acid-base disturbances. Coronary artery
      disease management includes use of antianginal drugs and revascularization of
      coronary arteries with angioplasty +/- stent placement or coronary artery bypass
      grafting. The long-term outcomes of these procedures need to be assessed and
      improved. Hypertension occupies a major role in the pathogenesis of heart disease
      in ESRD, and early and adequate control of hypertension is likely to have a major
      impact on the progression of cardiac disease. This entails the achievement of
      optimal volume status, combined with the appropriate use of antihypertensive
      agents such as calcium channel blockers, beta-blockers, angiotensin-converting
      enzyme (ACE) inhibitors, vasodilators, alpha-blockers, and central sympatholytic
      drugs. In ESRD patients, specific dialysis-related complications such as
      intradialytic hypotension and pericardial effusion may have additional effects on
      cardiac function and require attention. The choice of dialysate composition and
      membrane may influence clinical outcomes with specific effects on cardiac
      performance.

PMID- 9239430
TI  - Peer resource consulting: redesigning a new future.
AB  - The current case describes a young woman with diabetes mellitus who developed end
      stage renal disease (ESRD) and many other devastating complications related to
      her primary illness. Her experience illustrates many ways in which complicated
      illness can interrupt life's plans, dashing any dreams that she or her family
      might have for the future. Yet her story also illustrates the important role that
      a trained Peer Resource Consultant (PRC) can play in helping to better understand
      chronic illness, face and grieve losses, and even design new plans and create new
      dreams for the future. The discussion that follows includes several perspectives
      that offer poignant insight into the difficult situations characterized by the
      young diabetic with ESRD.

PMID- 9239431
TI  - Central venous catheters for maintenance hemodialysis: a cautionary approach.
AB  - There is an increasing trend toward the use of indwelling central venous
      catheters (CVC) for maintenance hemodialysis. Although such devices are necessary
      in some problematic cases, the general use of CVC is worrisome. Not only may CVC
      prejudice the ultimate success of future permanent vascular access, but CVC also
      may be associated with reduced dialysis delivery and with several important
      complications. This review summarizes recent developments in catheter design,
      placement techniques, maintenance of the indwelling catheter, and complications
      of CVC use. Based on cumulated experience, a judicious position is taken that
      recognizes the place of CVC among the various access options but that favors
      permanent vascular access whenever feasible.

PMID- 9239432
TI  - Stranger in my body.

PMID- 9239433
TI  - To dialyze or not to dialyze: an ethical and evidence-based approach to the
      patient with acute renal failure in the intensive care unit.
AB  - Patients with acute renal failure in the intensive care unit have high in
      hospital mortality. In this setting, decision making with regard to the
      initiation or discontinuation of dialysis by physicians, patients, and families
      is challenging because of the desire of all for the patient to recover while
      sparing unnecessary suffering. Decision making can be facilitated by knowledge of
      outcomes of the treatment of such patients in the medical literature. This
      knowledge assists nephrologists to distinguish those patients whose clinical
      situation indicates a more favorable prognosis from those whose prognosis is
      uncertain or definitely poor even with dialysis. This information, combined with
      consideration of relevant ethical guidelines, provides a framework for
      nephrologists to make decisions that are evidence based and ethically sound. We
      present and discuss two cases to show the application of evidence-based medicine
      and ethical considerations to decision making for patients with acute renal
      failure in the intensive care unit.

PMID- 9239434
TI  - Birthweight for length: ponderal index, body mass index or Benn index?
AB  - This study compares how effectively the ponderal index and the body mass index
      adjust birthweight for length at different gestations, and derives an improved
      index suitable for all gestations. The study was a cross-sectional survey, in a
      London teaching hospital, using a total of 999 neonates of 33 weeks gestation or
      later. Main outcome measures were the ponderal index (birthweight/length3), body
      mass index (birthweight/length2), and Benn index (birthweight/length(n)), where
      the length power n varies with gestation and is estimated by log-log regression.
      Results showed that up to 39 weeks gestation, the ponderal index is uncorrelated
      with length and so is a good index of birthweight for length. Past 39 weeks
      gestation, the ponderal index is negatively correlated with length, while the
      body mass index is uncorrelated, so that the body mass index is better. Neither
      index is optimal at all gestations. Deriving the Benn index
      (birthweight/length(n)) for each week of gestation, choosing n to make the index
      uncorrelated with length, shows that n falls steadily and very significantly (p <
      0.0001) with increasing gestation. This in turn means that predicted birthweight
      for length depends on gestation: for a neonate 48 cm long, predicted birthweight
      varies from 2485 g at 34 weeks to 3030 g at 43 weeks, a 20% range. However, for a
      54 cm long infant, predicted birthweight is the same at all gestations. A Benn
      index where the value of n changes linearly with gestation is described. We
      conclude that the ponderal index is not appropriate for measuring intra-uterine
      malnutrition, as it fails to adjust for length at all gestations. No other index
      of birthweight/length(n) with constant n is any better, as different gestations
      require different indices. Birthweight predicted from an infant's length depends
      on the infant's gestation. If, as Barker proposes, thinness at birth assessed by
      birthweight for length is used to predict later health status, more account needs
      to be taken of the complex relationship between birthweight, length and
      gestation.

PMID- 9239435
TI  - Respiratory symptoms and pulmonary function in a group of women weavers in South
      Africa.
AB  - Respiratory symptoms and ventilatory capacity were studied in 97 women carpet
      weavers in a hand-made carpet weaving industry in Umtata, Transkei, South Africa.
      The controls were from a bottling plant in the same city. Both groups were Black
      Africans from the Xhosa-speaking population. The population we studied were non
      smokers and there was no significant difference in age, race or height between
      the groups. The exposed weavers had significantly lower forced expiratory indices
      than the control group. Mean forced expiratory volume in 1 second (FEV1), forced
      mid-expiratory flow (FEF 25-75%), forced expiratory flow between 200 ml and 1200
      ml of forced vital capacity (FEF 200-1200), and peak expiratory flow (PEF) were:
      26.0%, 39.0%, 36.4% and 28.5% lower respectively in the exposed group compared
      with the controls. Mean forced vital capacity (FVC) and forced expiratory ratio
      (FEV1/FVC x 100) were 22.0% and 6.6% lower respectively in the exposed group
      compared with the controls. The percentage predicted (%pred) values of FVC, FEV1,
      FEV1/FVC ratio, FEF 25-75%, FEF 200-1200, and PEF in the exposed group were
      82.9%, 77.1%, 95.6%, 64.6%, 72.2% and 82.8%, respectively. The prevalence of
      FEV1/FVC ratio less than 70% in the exposed group was 37.2%, while in the
      controls it was 12%. The exposed group reported a significantly higher prevalence
      of respiratory symptoms compared to the control. The prevalence of nasal symptoms
      and cough was 62.8% and 58.1%, respectively in the weavers. Weavers who reported
      cough, breathlessness, and wheezing had significantly (p < 0.01) lower pulmonary
      function than those who did not report these symptoms. The present study
      demonstrates that the continual exposure to dust in weavers in this industry is
      associated with significantly lower pulmonary function, higher prevalence of
      respiratory symptoms, and weavers show signs of airway obstruction compared to
      workers not exposed to this type of dust. Women in the weaving industry have a
      significant occupationally related respiratory impairment.

PMID- 9239436
TI  - Mini-knemometry: an accurate technique for lower leg length measurements in early
      childhood.
AB  - A novel miniaturization of knemometry for accurate measurements of the lower leg
      length in prematures, newborns and infants (mini-knemometry), is presented. The
      study was performed in four healthy neonates, born at term, and one infant, born
      in the 34th week of gestation, measured daily for periods of 40 days; and in two
      monozygotic healthy twin sisters, born in the 32nd week of gestation, measured
      daily for periods of 58 days. Each of the 316 measurements consisted of four
      independent subsequent estimations of the distance between heel and knee, which
      are grasped by two metallic holders under light compression of 2.0-3.0 N. After
      an initial training of 1 week the technical error is 144 microns. Lower leg
      growth is non-linear (p < 0.001) with periods of stunted, and periods of
      accelerated, growth velocity.

PMID- 9239437
TI  - Assessment of body hydration in subjects with schistosomiasis.
AB  - Total body water (TBW) was measured by deuterium oxide dilution (D2O) and
      predicted by bioelectric impedance analysis (BIA) (Deurenberg, Schouten, Andreoli
      and De Lorenzo 1993) in 21 subjects with Schistosoma mansoni infection and 17
      healthy controls of similar age (32.8 +/- 13.7 years, n=38). Patients were
      selected to have no visible fluid retention and no cardiac or renal
      abnormalities. Body hydration (TBW per kg of body weight) was significantly
      higher in patients with schistosomiasis than in controls (62.9 +/- 3.6 vs 57.4 +/
      4.3%, p < 0.0005). A significant correlation was found between albumin levels
      and TBW% on the pooled sample (n=38; r=0.660, p < 0.0001). This relationship was
      not influenced by the presence of disease, as determined by ANCOVA. Values of TBW
      predicted by BIA were highly correlated and not significantly different (p=n.s.,
      ANOVA) from those measured by D2O in both controls and patients (r=0.854, p <
      0.001, SEE = 2.3 1, CV=5.9% and r=0.848, p < 0.001, SEE=4.0 1, CV=9.3%,
      respectively). The bias (TBW by BIA - TBW by D2O) was of 0.9 +/- 3.7 in controls
      and of -1.3 +/- 4.2 1 in patients. This bias was significantly correlated to TBW%
      in patients (r=0.575, p < 0.05) but not in controls (p=n.s.). It is concluded
      that subjects with schistosomiasis show an apparent subclinical increase in body
      hydration which could affect the prediction of TBW from BIA.

PMID- 9239438
TI  - Skeletal muscle fibre type and capillary density in college-aged blacks and
      whites.
AB  - The purpose of this study was to compare muscle fibre type proportions and
      capillary density in untrained, college-aged blacks (n = 14) and whites (n = 14).
      Both groups were similar in terms of peak oxygen uptake (VO2peak), measured
      during cycle ergometry (blacks: 42.6 +/- 4, whites: 44.3 +/- 4 ml.kg-1 min-1,
      mean +/- SD). Muscle samples were obtained from the quadriceps femoris (vastus
      lateralis) by the needle biopsy technique. Fibre type was determined by myosin
      ATPase stain (pH = 4.54) and capillaries were identified by amylase-periodic acid
      Schiff (PAS) stain. The percentage of type I, IIa, and IIb fibres in the blacks
      was 39.5 +/- 11.5, 40.0 +/- 8.4, and 22.8 +/- 9.8, respectively. In whites the
      percentage of type I, IIa, and IIb fibres was 44.9 +/- 8.5, 36.6 +/- 6.9, and
      18.3 +/- 9.6, respectively. No significant differences were noted between the two
      racial groups for type I, IIa, or IIb fibres. Capillary density was 277 +/-
      39/mm2 in the blacks compared to 289 +/- 32/mm2 in the whites. Capillary density
      was positively correlated to percentage of type I fibres (r = 0.497) and
      negatively correlated to percentage of type IIa fibres (r = -0.389), in the
      overall study population. These data suggest that if racial differences in fibre
      type do exist, such differences are small compared to the variability in this
      measure.

PMID- 9239439
TI  - Blood pressure variation among Ethiopians on the Simien Plateau.
AB  - This report presents information on determinants of blood pressure variation in a
      rural sample of 263 Ethiopian highlanders 14-86 years of age, resident at 3530 m
      on the Simien Plateau. Mean systolic and diastolic blood pressures for males and
      females were 109/ 75 and 106/73, respectively, and there were no age differences.
      These findings confirmed that men and women can have low normal blood pressure
      throughout adulthood. Blood pressures increased with increasing body mass index
      (BMI) among adult males, although the mean BMI of 19.1 kg/m2 was low compared
      with US values. This illustrates that BMI variation may be associated with blood
      pressure variation in men even at low mean values of both. Blood pressure did not
      vary with adult haemoglobin concentration.

PMID- 9239440
TI  - Socioeconomic factors and growth during childhood and early adolescence in Jena
      children.
AB  - The influence of socioeconomic parameters (number of children in the family,
      birth order of subject, professional status of the father, education of the
      mother) and background characteristics (birth length, birth weight and age of the
      mother at birth of the child) of growth in body height in children from 4 to 12
      years of age was investigated. The analysis is based on data from a longitudinal
      growth survey, which started with 207 children (98 males and 109 females) from
      Jena (Germany) in 1985. Multiple regression analysis was used to estimate the
      degree of relationship between height and the social or background factors. In
      this study no differences in growth between children of different social groups
      were found. Variation in height of girls was mainly affected by the biological
      factor length at birth of the child.

PMID- 9239441
TI  - Prediction of total body water in Indian men from anthropometry and bioelectrical
      impedance using deuterium dilution as reference.
AB  - Total body water (TBW) obtained by deuterium dilution (TBWD) in 45 adult Indian
      males of low body mass index was compared with values obtained from bioelectrical
      impedance (TBWImp) and two anthropometry-based prediction equations.
      Bioelectrical impedance significantly underestimated TBW when compared with
      deuterium dilution, by 2.75 SD 2.86 kg. Comparisons of the anthropometry-based
      prediction equations demonstrated that TBW was overestimated by 0.87 SD 2.49 kg,
      and 2.47 SD 2.57 kg, respectively. Since all parameters in the bioelectrical
      impedance method were standardized, the difference in the values could have been
      because of the equation used. Therefore, a fresh equation for the measurement of
      TBW by the bioelectrical impedance method was derived using the variables of
      height2/impedance and weight. New prediction equations for TBW were also derived
      based on anthropometric variables of weight and height. Body weight has the
      greatest influence in the prediction equations for TBW, and the equation derived
      was TBW (kg) = 0.533 x body weight (kg) + 3.77, SEE = 2.4 kg. Using
      height2/impedance gave the relationship: TBW (kg) = 0.568 body weight-0.04
      height2/impedance + 4.35, SEE = 1.9 kg.

PMID- 9239442
TI  - A cross-sectional growth study of trunk and limb segments of the Bengali boys of
      Calcutta.
AB  - This report deals with cross-sectional growth of sitting height (SH), subischial
      length (SL, estimated as height minus sitting height), height of the anterior
      superior iliac spine (HIS), and total arm length (TAL) of Bengali school boys
      (Calcutta), aged 7.0-16.0 years. Preece-Baines model 1 (PB1) fits to the cross
      sectional means of the four traits estimate the average ages at maximum increment
      at 12.41 years for SL, at 12.43 years for HIS, at 12.97 for TAL, and at 13.74
      years for SH. Maximum increment of the upper and lower segment of the body are
      reached at an earlier age in the present study than in a longitudinal analysis of
      semi-urban Bengali boys from the suburban area of Calcutta. Socioeconomic
      differences and secular trend might explain this shift towards earlier
      maturation.

PMID- 9239443
TI  - Brachymetacarpia V in familial short stature.
AB  - This study was planned to search for the presence of possible tubular bone
      abnormalities in familial short stature (FSS) as has been previously noted in
      some reports. Twenty-five (17 male, 8 female) children with FSS aged 10.0 SD 3.6
      years were taken as the study group, and 23 (14 male, 9 female) children of
      normal stature aged 10.6 SD 2.7 years comprised the control group. FSS was
      defined as height of the child and mean parental height below 3rd centile line,
      normal growth velocity and bone age within 2 years of chronological age. Other
      causes of short stature were ruled out. Height, weight, sitting height and arm,
      forearm and upper arm length measurements were taken by standard methods. A left
      hand and wrist X-ray was taken to evaluate the length of the 5th metacarpal.
      Children with FSS had a significantly higher prevalence of brachymetacarpia V
      (64%) than the children with normal stature (21.7%) (p < 0.001). Other tubular
      bone parameters, however, were normal. Sitting height/height ratios were in
      normal ranges and comparable in FSS and the control group. Similarly arm to
      height and upper arm to forearm ratios were comparable in the two groups
      excluding disproportionate shortening of the limbs. The finding of increased
      incidence of brachymetacarpia V in FSS may suggest an underlying tubular bone
      abnormality, which may explain the short stature in FSS.

PMID- 9239444
TI  - Effect of the haloperidol tetrahydropyridine metabolite 4-(4-chlorophenyl)-1-[4
      (4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine on dopamine receptor and
      transporter binding. A nonhuman primate 123I-iodobenzamide and 2 beta
      carbomethoxy-3 beta-(4-iodophenyl)tropane single photon emission computed
      tomographic study.
AB  - Researching the biological activities and toxicities of metabolites of drugs is
      of growing importance and has received increasing attention during the last
      decade in order to gain a better understanding of the efficacy and safety profile
      of drugs in clinical use. HPTP (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4
      oxobutyl]-1,2,3, 6-tetrahydropyridine, CAS 52669-92-8), the tetrahydropyridine
      metabolite of the classical neuroleptic, haloperidol (CAS 52-86-8), has recently
      been the focus for further understanding the well-known side effect profile of
      haloperidol. The current study was aimed at investigating the effect of HPTP
      treatment on dopamine receptor and transporter binding in the nonhuman primate,
      i.e. the baboon Papio ursinus. The study was performed using the dopamine
      receptor ligand, 123-I-iodobenzamide (IBZM) and the dopamine transporter ligand,
      [123]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) in planar
      scintigraphy and single photon emission computed tomographic (SPECT) protocols.
      Dopamine receptor binding in the striatum was measured from the time activity
      curves by calculating the IBZM ratios of the basal ganglia to frontal cortex and
      of the basal ganglia to cerebellum. 99mTc-HMPAO (hexamethylpropylene amine oxime)
      SPECT detected no changes in striatal perfusion during HPTP treatment. The
      transporter binding was measured by dynamic imaging of the basal ganglia, frontal
      cortex and cerebellum using beta-CIT. IBZM dopamine receptor binding is initially
      (as measured after 18 weeks treatment) decreased by HPTP treatment in the basal
      ganglia, frontal cortex (not significantly) and cerebellum but reversed to
      control values in the frontal cortex, as measured after 58 weeks treatment with
      HPTP. The binding to the basal ganglia and to a lesser degree the cerebellum is
      still affected after 58 weeks treatment with HPTP but indicates a tendency to
      return towards the control values. The results of the planar dynamic study with
      beta-CIT indicate a decrease in the beta-CIT binding to the dopamine transporters
      in the basal ganglia and to a lesser extent the cerebellum as measured by the
      time activity and percentage washout rate of the beta-CIT in the HPTP treated
      baboons. The effect of HPTP on the serotonin transporters appears to be minimal
      as observed from the results obtained from the frontal cortex. These results
      indicate that HPTP treatment influences both presynaptic and postsynaptic
      neurofunction in the dopaminergic neurones.

PMID- 9239445
TI  - Neuroprotective effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid in
      the gerbil model of transient global cerebral ischemia.
AB  - Effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2
      amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was
      examined in a mongolian gerbil model of global cerebral ischemia. Effect of CGP
      40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4
      phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under
      the same conditions. Drugs were administered intraperitoneally 30 min before
      bilateral carotid artery occlusion. At 4 days after the ischemia, locomotor
      activity was significantly higher in ischemic control mongolian gerbils in
      comparison with sham-operated mongolian gerbils. CGP 40116 at the dose of 10
      mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly suppressed the
      increase of the motility. Seven days after ischemia, ischemic control group was
      still hyperactive compared to sham-operated group. CGP 40116 at the dose of 10
      mg/kg and CGS 19755 at the dose of 30 mg/kg significantly reversed it. The number
      of survived neurons of ischemic control group was significantly less than that of
      sham-operated group at 7 days after ischemia. CGP 40116 at the dose of 10 mg/kg
      and CGS 19755 at the dose of 30 mg/kg significantly increased the number of
      survived neurons. It is concluded that CGP 40116 is more potent for amelioration
      of global cerebral ischemic damage than CGS 19755.

PMID- 9239446
TI  - Effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid on focal cerebral
      ischemia in cat.
AB  - The effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2
      amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was
      examined in a cat model of focal cerebral ischemia. Effect of CGP 40116 was
      compared to that of another competitive NMDA antagonist, (+/-)-cis-4
      phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under
      the same conditions. Drugs were administered intravenously 30 min before left
      middle cerebral artery (MCA) occlusion. After MCA occlusion for 8 h, infarction
      spreaded widely among caudate nucleus prepyriform cortex, amygdala and temporal
      lobe cortex in the ischemic hemisphere. CGP 40116 at the dose of 10 mg/kg and CGS
      19755 at the dose of 30 mg/kg significantly decreased the infarcted area. CGP
      40116 was effective in the frontal and central brain, although CGS 19755 showed
      neuroprotective effect in almost all sites. Thus, the compounds are potent
      neuroprotectants in focal ischemia.

PMID- 9239447
TI  - Pharmacological properties of the new centrally acting muscle relaxant (R)-(+)-3
      phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride.
AB  - The pharmacological properties of (R)-(+)-3-phenyl-5-[2-(1
      pyrrolidinylmethyl)butyryl]isoxazole hydrochloride (CAS 144576-50-1, MS-322), a
      new centrally acting muscle relaxant, were investigated and compared with those
      of eperisone-HCl (CAS 56839-43-1) in experimental animals. MS-322 (1.5-6 mg/kg
      i.v.) reduced both anemic and intercollicular decerebration-induced rigidity in
      rats. Similar doses were required for these effects. The activity of MS-322 (200
      mg/kg p.o.) against intercollicular decerebration-induced rigidity was greater
      and longer lasting than that of the same dose of eperisone-HCl. MS-322 (0.75-6
      mg/ kg i.v.) inhibited the flexor reflex in anesthetized cats in a dose-dependent
      manner and more strongly than eperisone-HCl. MS-322 had no effect on the
      neuromuscular junction in anesthetized rats. The muscle relaxant activity of MS
      322 in mice, demonstrated by the traction and rota-rod tests was stronger than
      that of eperisone-HCl, whereas MS-322 affected spontaneous motor activity in mice
      less than eperisone-HCl. The results of this study suggest that MS-322 is a
      potent centrally acting muscle relaxant with relatively weak depressant activity
      at other central nervous system pathways.

PMID- 9239449
TI  - Studies on the bioavailability of glyceryl trinitrate after sublingual
      administration of spray and tablet.
AB  - The plasma profiles of nitroglycerin (glyceryl trinitrate, GTN, CAS 55-63-0) were
      estimated after two sublingual puffs of 0.4 mg GTN from a fluorochlorohydrocarbon
      (FCH)-free oral spray and one sublingual tablet of 0.5 mg GTN (Nitromex). The
      study was carried out in an open, randomized, two-phase, cross-over design with
      24 volunteers. Eighteen blood samples were taken within 30 minutes after
      administration, and the plasma concentrations of GTN were determined by a
      specific gas chromatographic method with electron capture detection. The
      pharmacokinetic parameters, Cmax, tmax, and AUC, were determined for each
      volunteer. After correction of the AUC and Cmax values of the oral spray by
      dividing by two, the ratios (spray/tablet) of the AUC and Cmax and the 90%
      confidence intervals were estimated. The plasma concentrations of GTN (mean)
      after the spray (dose: 0.8 mg GTN) reached a maximum of 3.96 ng/ml (range: 0.99
      10.86) at 3.5 minutes (range: 2-5). The plasma concentrations of GTN (mean) after
      the tablet (dose: 0.5 mg GTN) reached a maximum of 1.97 ng/ml (range: 0.57-4.33)
      at 4.9 minutes (range: 3-7). The corrected ratios (spray/tablet) of AUC and Cmax
      were 1.02 and 0.97 with the 90% confidence intervals (0.80, 1.30), respectively
      (0.77, 1.24). The results indicate that the oral spray in a dose of 0.4 mg is
      equivalent to the sublingual tablet in a dose of 0.5 mg.

PMID- 9239448
TI  - Influence of acetylcysteine on aggravation of ischemic damage in ex vivo hearts
      of rats exposed to hyperbaric oxygen.
AB  - Rats were exposed to hyperbaric oxygen (HBO = 100% oxygen; 2.5 atmospheres
      absolute pressure) for 6 h. Isovolumic left heart preparations from these animals
      were subjected to global low flow-ischemia (perfusion rate from 12 ml/min to 2
      ml/min for 40 min) and reperfusion. Hearts from rats not exposed to HBO underwent
      the same ischemic-reperfusion procedure (controls). As compared to control, HBO
      treatment caused in ex vivo hearts a significant aggravation of cardiac ischemic
      picture as indicated by a marked increase in left ventricular end diastolic
      pressure (LVEDP) and reduced post ischemic left ventricular developed pressure
      (LVDP). At the end of the ischemic and reperfusion periods LVEDP values were 6.8
      (p < 0.001) and 8 (p < 0.001) times higher than the corresponding control values.
      Moreover, LVDP and coronary perfusion pressure (CPP) values were decreased (2.8
      times; p < 0.001) and increased (56%; p < 0.001), respectively, as compared to
      control preparations. These events were also associated with a considerable
      impairment of the cardiac tissue to generate 6-keto-PGF1 alpha. Treatments of
      rats with different doses of acetylcysteine (N-acetylcysteine, CAS 616-91-1, NAC;
      0.25-0.5-1 g/kg p.o.) before HBO displayed a clear-cut and dose-related
      protective activity in hearts subjected to ischemia-reperfusion. Also the
      generating capacity of 6-keto-PGF1 alpha from these hearts were restored
      according to the dose of NAC employed. When aortic rings from rats exposed to HBO
      were considered, they showed a reduced capacity to release 6-keto-PGF1 alpha and
      an increased sensitivity to endothelin-1. At the same time, the relaxant activity
      of acetylcholine in these tissues was almost lost. Again, NAC treatment of the
      animals before HBO restored in a dose-dependent way the capacity of the aortic
      rings to generate 6-keto-PGF1 alpha. This event was paralleled by normalized
      responses of the preparations to endothelin-1 and acetylcholine. Taken together
      these results clearly indicate that acute HBO treatment of the rats markedly
      aggravates the ischemic-reperfusion damage in ex vivo hearts. This event is
      coupled with a compromised integrity of cardiac and extracardiac endothelial cell
      functions. The protective activity of NAC observed in this study once more
      emphasises its therapeutic role in increasing antioxidant defence mechanisms.

PMID- 9239450
TI  - Possible involvement of ATP-dependent K-channel related mechanisms in the
      antihypertensive and cough suppressant effects of the novel ACE inhibitor (2S,
      3aS, 7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D-glutamyl)octahydro-1H- indole-2
      carboxylic acid.
AB  - The antihypertensive and cough suppressant mechanisms of DU-1777 ((2S,3aS,7aS)-1
      (N2-nicotinoyl-L-lsyl-gamma-D-glutamyl )octahydro-1H-indole-2 -carboxylic acid,
      CAS 116662-73-8), a new long-acting angiotensin-1-converting enzyme (ACE)
      inhibitor, were investigated in vivo and in vitro. The antihypertensive effects
      of DU-1777 at 10 mg/kg p.o. and cromakalim at 0.3 mg/kg p.o. were partially
      (about 60%) or fully antagonized by glibenclamide at 10 mg/kg i.v. in 2-kidney, 1
      clip renal hypertensive rats (2K-1C RHR). The antihypertensive effects of a Ca
      blocker (nifedipine) and other ACE inhibitors (captopril, alacepril, enalapril,
      lisinopril, imidapril and quanapril) were not antagonized by glibenclamide. In
      deoxycorticosterone acetate-salt hypertensive rats (DOCA-HR), the
      antihypertensive effects of DU-1777 at 3-30 mg/kg p.o. were fully antagonized by
      glibenclamide. However, in vitro, DU-1777 (10(-6)-10(-3) mol/l) did not affect
      aortic ring contractions induced by high K (30 mmol/l). In guinea pig, citric
      acid induced cough was increased by ACE inhibitors, captopril, alacepril,
      enalapril and lisinopril (10 and 30 mg/kg p.o.). DU-1777 had a tendency to
      decrease citric acid induced cough and the effect was antagonized by
      glibenclamide. These results suggest that while DU-1777 itself does not open ATP
      dependent K channel, it indirectly produces these effects through unknown
      mechanisms in vivo. Moreover, these effects contributed to the antihypertensive
      effect in DOCA-HR and cough suppressant effect in guinea pigs.

PMID- 9239451
TI  - Effects of clonidine in a primed rat model of acute hepatic porphyria.
AB  - Acute hepatic porphyrias can be induced by several drugs and acute attacks of
      porphyrias are often associated with severe hypertension. Therefore it is
      important to know if an antihypertensive drug used has porphyrogenic potency or
      not. As previously demonstrated in normal rats the alpha-receptor blocker
      clonidine (CAS 4205-90-7) has no significant influence on the porphyrin
      metabolism. Pretreatment of rats with 3,5-diethoxycarbonyl-1,4-dihydrocollidine
      (DDC) or allyl-isopropyl-acetamide (AIA) induces hepatic delta-aminolaevulinic
      acid synthase (ALA-S) and increases the urinary excretion of porphyrin precursors
      (ALA and PBG) comparable to the latent phase of acute hepatic porphyrias in
      humans. Clonidine did not induce hepatic ALA-S or urinary excretion of ALA or PBG
      in normal as well as in DDC or AIA pretreated rats. Moreover the induction of
      P4501A1 (7-ethoxyresorufin-O-deethylase) by DDC was abolished by simultaneous
      application of clonidine. From these findings one can probably conclude that
      clonidine is a safe drug in human acute hepatic porphyria.

PMID- 9239452
TI  - Pharmacokinetics of miglitol. Absorption, distribution, metabolism, and excretion
      following administration to rats, dogs, and man.
AB  - The absorption, distribution, metabolism, and excretion of miglitol
      ((2R,3R,4R,5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-piperidinet riol, CAS
      72432-03-2, BAY m 1099) have been studied following single and repeated
      administration of non-labelled and radiolabelled (3H, 14C) drug to rats, dogs,
      and human volunteers via different routes of administration (intravenous, oral,
      intraduodenal) and at various doses (0.3-450 mg/kg). After intravenous
      administration, miglitol is excreted rapidly and completely via the renal route.
      No indication was found for a metabolization of radiolabelled miglitol. The
      (renal) clearance of miglitol is in the range of the glomerular filtration rate.
      Miglitol is rapidly eliminated from plasma with apparent elimination half-lives
      of 0.4-1.8 h. Miglitol is virtually not bound to plasma proteins. After oral
      administration miglitol is rapidly and at low doses also completely absorbed. At
      higher doses (> or = 5 mg/kg in rats and dogs, > 50 mg in humans) a saturation of
      absorption becomes evident. Miglitol is distributed predominantly in the
      extracellular space. The volumes of distribution are low (0.3-0.8 l/ kg). In rats
      high concentrations were initially found in the kidneys, the blood and some well
      perfused tissues. The permeation across the blood/brain barrier is very low.
      Elimination from organs and tissues occurs rapidly resulting in very low residual
      radioactivity in the body 2 days after dosing (< 0.9% of the dose). At this very
      low concentration level a terminal elimination phase of radioactivity
      characterized by half-lives of 50-110 h was observed giving rise to a slight
      tendency for accumulation (accumulation factors < 6) following repeated
      administration to rats. In pregnant rats [14C]miglitol crossed the placental
      barrier slowly and to a limited extent. In lactating rats miglitol was found in
      milk in concentrations similar to those in the maternal plasma.

PMID- 9239453
TI  - Enhancement of alcohol-induced hypoglycaemia by H2-receptor antagonists.
AB  - The oral ethanol loading test (0.5 g/kg body mass) was carried out in 3 groups
      with 10 healthy male volunteers each before and after 7 days of administration of
      either cimetidine (CAS 51481-61-9), ranitidine (CAS 66357-59-3), or famotidine
      (CAS 76824-35-6). The parameters determined during 6 h comprised the blood levels
      of ethanol, acetaldehyde, glucose, lactate, pyruvate and bicarbonates, as well as
      blood pH, PCO2 and PO2. Only ranitidine significantly increased the mean blood
      ethanol concentration and none of the drugs modified the blood acetaldehyde
      concentration. Hypoglycaemia following alcohol ingestion was significantly
      enhanced by all H2-receptor antagonists, but was most pronounced after
      famotidine. The alcohol-induced rise in blood pyruvate and lactate rather had a
      tendency to decrease during the second test. The presented results suggest that
      the evident enhancement of alcohol-induced hypoglycaemia by H2-receptor
      antagonists is not dependent on the increase of ethanol absorption from the
      gastrointestinal tract, but represents rather a specific effect of these drugs on
      glucose metabolism.

PMID- 9239454
TI  - Preliminary toxicokinetic study with different crystal forms of S (+)-ibuprofen
      (dexibuprofen) and R,S-ibuprofen in rats.
AB  - The aim of the study was to gain information on the plasma concentration-time
      profiles of both ibuprofen (CAS 15687-27-1) enantiomers in the rat after single
      oral application of two different crystal forms of S (+)-ibuprofen (dexibrufen,
      CAS 51146-56-6) and racemic ibuprofen in order to optimize blood-sampling times
      in a subsequent subchronic toxicity study. The application of either commercial
      racemic ibuprofen or recrystallised S (+)-ibuprofen (60 mg/kg) to two groups of 4
      rats per blood sampling term was carried out in order to define Cmax and tmax and
      AUC of the plasma-concentrations of the ibuprofen enantiomers. The crystals of
      commercial (manufactured according to an usual manufacturing procedure) and
      recrystallised (S(+)- and racemic ibuprofen were different in respect to their
      shape and size. The recrystallised crystal species of S (+)- and racemic
      ibuprofen has better galenic (tabletting-) properties and tablets containing the
      modified S (+)-ibuprofen species showed favorable clinical results. The
      toxicokinetic behaviour of the recrystallised species was investigated in
      comparison to the commercial crystal species because of its slightly but
      significantly slower dissolution rate in simulated gastric and enteric juice. As
      the AUC0-24 h S-(+)-ibuprofen and the AUC0-24 h, R-(-)-ibuprofen after
      application of commercial and recrystallised crystal species were not different,
      the crystal form apparently did not exert an influence on the extent of
      absorption of S-(+)-ibuprofen and racemic ibuprofen in the rat. The rat has a
      high inversion capacity and the inversion of R-(-)-ibuprofen after application of
      commercial and recrystallised racemic ibuprofen was nearly complete in this
      study. The effects of crystallinity on solubility in simulated media in vitro did
      not correlate to the findings on the extent of absorption in the rat in vivo.

PMID- 9239455
TI  - Absorption of oral lornoxicam in healthy volunteers using a granular formulation
      in comparison with standard tablets.
AB  - The bioavailability of lornoxicam (CAS 70374-39-9), a novel highly potent anti
      inflammatory and analgesic agent, was studied in healthy volunteers after single
      doses of a new oral formulation (8 mg granules) in comparison to tablets (8 mg).
      Eighteen healthy volunteers (6 males and 12 females) with a mean age of 29.4 were
      given a single 8 mg dose of each formulation in an open, cross-over study, with
      randomised sequences. Lornoxicam plasma levels were determined by an HPLC method.
      Cmax, AUC0-infinity and t 1/2 beta values were similar for both the granules and
      tablets, but tmax and lag time values after lornoxicam granules were
      significantly shorter than after the tablets. During the study, no side-effects
      were noted with either of the formulations studied. Therefore this study showed
      that lornoxicam granular formulation had a faster absorption than tablets even
      though the two formulations can be considered bioequivalent.

PMID- 9239456
TI  - Plasma profiles of transdermal 17 beta-estradiol delivered by two different
      matrix patches. A four-way cross-over study in postmenopausal women.
AB  - The aim of this study was to investigate the systemic bioavailability and plasma
      profiles of 17 beta-estradiol (CAS 50-28-2, E2) after the application of two
      types of matrix patches for the transdermal delivery of E2: MenorestTM (the test
      patch) with delivery rates of 37.5, 50 and 75 micrograms E2/day and a reference
      patch with a delivery rate of 50 micrograms E2/day. All 3 test patches were
      identical in composition, achieving different transdermal E2 delivery rates by
      variations in the surface area (11.0, 14.5 and 22.5 cm2). All 4 patches were each
      worn by 24 postmenopausal women over a 4-day period (i.e. 96 h), each of the 4
      treatment periods being separated by a 7-day wash-out period according to a
      randomized, 4-way crossover design. Blood samples were collected before and 3, 6,
      9, 12, 24, 34, 48, 58, 72, 84, and 96 h after each patch application. Plasma E2
      concentrations were determined by a specific direct radioimmunoassay method. The
      following pharmacokinetic parameters were evaluated: AUC0-96h; Cmax, tmax, Cmin,
      Caverage. The course of the E2 plasma levels over the total test period (96 h)
      was relatively constant for all patches. For the test patch, a linear
      relationship between the pharmacokinetic parameters and the different patch areas
      (i.e. dosages of 37.5, 50, 75 micrograms E2/d) could be shown (correlation
      coefficient 0.99). The resulting Cmax values for the patch were: 44.2, 58.3, and
      92.1 pg E2/ml, corresponding to Caverage values of 39.5, 45.5, and 70.6 pg E2/ml.
      The reference patch and the test patch, at a dose of 50 micrograms E2/d, were
      similar in terms of Cmax, while the Caverage, AUC0-96h and Cmin were
      significantly higher with the test patch. The systemic bioavailability of the
      reference patch was comparable to that of the test patch at a dose of 37.5
      micrograms E2/d: AUC0-->96h 3017.5 +/- 1312.4 pg/ml.h for the reference patch and
      3375.9 +/- 1254.7 pg/ml.h for the test patch. A physical model for the
      calculation of the course of the E2 levels was used to describe the
      experimentally determined data. However, in the evening, periodically higher E2
      plasma levels were observed for all patches than in the morning. From these
      results it can be concluded that E2 plasma profiles produced by the test patch
      are reproducible, and in the physiological range consistent with the early to mid
      follicular level in the premenopausal woman over 4 days (96 h), correlating with
      the doses administered (37.5-50-75 micrograms E2/d). Additionally, the systemic
      bioavailability of the test patch at a dose of 37.5 micrograms E2/d is comparable
      to that of the reference patch at a dose of 50 micrograms E2/d.

PMID- 9239458
TI  - Synthesis and antimicrobial activity of beta-[(2-benzimidazolyl)thio]-beta
      benzoyl styrene derivatives.
AB  - In this study some new beta-[(2-benzimidazolyl)thio]-beta-benzoyl styrene
      derivatives have been synthesized by reacting 2-(phenacetylthio)benzimidazole and
      substituted benzaldehydes in piperidine/dry benzene. Structures were verified by
      microanalysis, IR and NMR spectral analysis. Antimicrobial activities of the
      compounds were investigated by the microdilution susceptibility test; Muller
      Hinton Broth and Sabouraud Dextrose Broth were used for the determination of
      antibacterial and antifungal activity. Test organisms: Staphylococcus aureus ATCC
      29213 and Enterococcus faecalis ATCC 29212 as Gram (+) bacteria, Escherichia coli
      ATCC 25922 and Pseudomonas aeruginosa ATTC 27853 as Gram (-) bacteria, and
      Candida albicans, Candida pseudotropicalis, Candida parapsilosis and Candida
      stellatoidea as yeast-like fungi. All the compounds showed good antimicrobial
      effect, especially against gram (+) bacteria. Among the compounds tested beta-[(2
      benzimidazolyl)thio]-beta-benzoyl-4-chloro styrene (compound 9), beta-[(2
      benzimidazolyl)thio]-beta-benzoyl-4-nitro styrene (compound 10) and beta-[(2
      benzimidazolyl)thio]-beta-benzoyl-4-acetylamino styrene (compound 11) showed the
      most favorable activity.

PMID- 9239457
TI  - Synthesis and antimycobacterial activity of nitroxanthones. 2nd communication:
      antimycobacterial activity.
AB  - The mono-, di-, tri- and tetranitroxanthones have been tested against different
      mycobacteria by means of the Agar diffusion method resulting in minimum
      inhibitory concentrations (MIC) and for more precise interpretation by means of
      the bacterial growth kinetics method. Nitroxanthones with the 2,4-dinitro
      substitution pattern show activities beyond 1 microgram/ml.

PMID- 9239459
TI  - Influence of selegiline and lipoic acid on the life expectancy of
      immunosuppressed mice.
AB  - Ten groups of 14 immunosuppressed NMRI-mice (nu/nu) were raised and kept under
      germ-reduced conditions. The control animals were fed a germ-reduced diet, nine
      other groups received the same diet with selegiline (CAS 14611-51-9, Deprenyl) or
      lipoic acid (thioctic acid, CAS 62-46-4) admixed at various amounts. The 50%
      survival rate, the total life span of each group and the areas under the curves
      were determined to evaluate life expectancy as compared to the controls. The
      racemate of lipoic acid at high dosage (350 mg/kg body weight) reduced the life
      span significantly. The S(-)-enantiomer of lipoic acid (75 mg/kg body weight)
      increased the 50% survival rate, whereas the physiologic R(+)-enantiomer (9 mg/kg
      body weight) expanded the total life span of its group. Alteration of only one
      out of three parameters was not considered significant. All other groups except
      for one did not differ from controls: only animals which obtained 75 micrograms
      selegiline per kg of body weight and per day exerted increased life expectancies
      by all three parameters. This group exhibited also in statistical evaluation a
      significantly (p < 0.05) prolongated survival time up to about 200% as compared
      to the control animals.

PMID- 9239460
TI  - Test-retest reliability and influence of practice effects on performance in a
      multi-user computerized psychometric test system for use in clinical
      pharmacological studies.
AB  - Fifty naive drug-free healthy young male or female volunteers performed
      psychometric tests on 6 sessions with 3- to 4-days intervals, using a new multi
      user computerized test system for use in clinical pharmacology. Tests of simple
      reaction time, complex reaction time, concentration, motor coordination, and
      short-term memory (word pairs or figures) were performed. Clear practice effects
      were shown for almost every psychometric variable recorded. The magnitude
      differed considerably between tests. The magnitude of practice effects was most
      evident (46.5-55.0%) for the concentration test, the coordination test, and the
      Vienna reaction test. Intermediate practice effects (20.8-31.0%) were observed
      with the complex reaction test (percent correct reactions) and both short-term
      memory tests (test duration). Only small practice effects (5.1-14.3%) were
      observed with the reaction times of the simple and the complex reaction test, and
      the percent correct responses in the short-term memory tests. After 3 test
      sessions, significant further improvements could not be shown for most tests, but
      for the reaction times in the simple and the complex reaction test this was true
      from the first or the second test session, respectively. For the concentration
      test and the coordination test, significant practice effects could be shown even
      after 5 training sessions. It is recommended to perform at least one training
      session before the start of clinical pharmacological studies with psychometric
      testing. Test-retest-reliability, as determined from session 5 to session 6 by
      Spearman's rank correlation coefficient (R8), was very good (> or = 0.95) for the
      concentration test (percent correct responses) and the coordination test (mean
      steering time). Most other variables showed intermediate (0.44-0.68) reliability
      (reaction times in the simple and complex reaction test, percent correct
      reactions in the complex reaction test, percent errors in the concentration test,
      test duration of the short-term memory tests). The percent correct answers, which
      is the primary variable in both short-term memory tests, had a relatively poor
      reliability (0.14-0.18).

PMID- 9239461
TI  - "Volunteer bias" in clinical pharmacological studies.

PMID- 9239462
TI  - Augmentation of host defence against bacterial and fungal infections of mice
      pretreated with the non-pathogenic Escherichia coli strain Nissle 1917.
AB  - Escherichia coli strain Nissle 1917 (DSM 6601, Mutaflor) was investigated for its
      ability to enhance the immune response against bacterial or fungal infections in
      vivo. Mice were infected intravenously with either 6 x 10(3) colony forming units
      (cfu) of Listeria monocytogenes bacteria or 5 x 10(5) Candida albicans cells. One
      day prior to infection, mice were treated orally with four different
      concentrations of E. coli strain Nissle 1917 (10(6), 10(7), 10(8), and 10(9)
      viable cells). Three days after infection with L. monocytogenes or one day after
      infection with C. albicans, mice were sacrificed and the parasite burden of the
      main target organs of the respective infection model were examined. The
      protective effect of E. coli strain Nissle 1917, compared to placebo-treated
      controls and to mice treated with a dose of 10(4). Units interferon gamma, is
      shown as the reduction of viable bacteria in spleen and liver or viable fungi in
      the kidneys of infected animals, respectively. Orally administered E. coli strain
      Nissle 1917 reduced Listeria monocyto-genes and Candida albicans in a dose
      dependent manner. Treatment with 10(9) cfu of E. coli bacteria led to a reduction
      of Listeria counts to 7.4% in spleen and 2.4% in liver. A more than 10-fold
      decrease of viable Candida albicans (residual parasitaemia 6.8%) in the kidneys
      of the infected animals was also achieved by this E. coli concentration. These
      results suggest that E. coli strain Nissle 1917 is a potent immunostimulator of
      bacterial origin with highly protective efficacy against pathogenic bacterial of
      fungal infections.

PMID- 9239463
TI  - Friction in hip prostheses.
AB  - Although the reduction of frictional torques was the driving force behind the
      design of the Charnley prosthesis, later concerns about wear and subsequent
      loosening of this and other hip replacements have dominated debate within the
      bioengineering community. To stimulate discussion on the role of friction in
      loosening, a review of the frictional characteristics of different prostheses was
      undertaken. The use of simple laboratory screening-type machines in the
      frictional assessment of different material combinations is discussed together
      with experiments performed on single axis simulators using both conventional and
      experimental prostheses. In particular, recent developments in the use of soft
      layer components are highlighted. Further, the possible link between excessively
      high frictional torques and loosening is discussed in the light of current
      results obtained from explanted prostheses.

PMID- 9239464
TI  - Formation and characteristics of the apatite layer on plasma-sprayed
      hydroxyapatite coatings in simulated body fluid.
AB  - Plasma-sprayed hydroxyapatite (HA) coatings were incubated in simulated body
      fluids (SBFs) for different periods of time to investigate the nucleation and
      growth of apatite on their surface. The layer that formed was recognized as
      having similarities to bone apatite because it is poorly crystallized, non
      stoichiometric or calcium deficient, and contains carbonate and magnesium.
      Scanning electron microscopy (SEM) and infrared spectroscopy (IR) were employed
      to investigate the morphological changes of the coating surface and the structure
      of the grown layer respectively. In the first few hours, calcium and phosphate
      ions dissolved from the coatings so as to increase their local supersaturation to
      a higher degree, thereafter followed by the nucleation and growth of apatite. The
      nucleation occurred firstly on the recessed regions, inside pores and cracks
      where the higher supersaturation was readily maintained. Only after 24 h
      incubation was a complete layer formed on the surface of the coating. There is no
      obvious interface between the grown layer and the underlying coating. Heat
      treatment in the air made the apatite transform into biphasic calcium phosphate
      of HA and tricalcium phosphate, with a blue colour because of trace manganese
      ions. The heat-treated HA coating showed no dissolution by SEM observation. This
      resulted in no precipitation on the surface. When SBF was used with two-fold
      higher ion concentrations, the apatite layer formed slowly in 72 h without
      dissolution of the coating surface. This may mean that the microenvironment with
      a sufficiently high degree of supersaturation of calcium and phosphate ions is
      crucial for apatite to nucleate and grow in SBF, while the HA crystalline
      structure is not critical in the nucleation process, as expected.

PMID- 9239465
TI  - Osteoclastic resorption of calcium phosphate ceramics with different
      hydroxyapatite/beta-tricalcium phosphate ratios.
AB  - To study the influence of calcium phosphate ceramic solubility on osteoclastic
      resorption, neonatal rabbit bone cells were cultured for 2 days on hydroxyapatite
      (HA), beta-tricalcium phosphate (beta-TCP) and two types of biphasic calcium
      phosphate (BCP) with HA/beta-TCP ratios of 25/75 and 75/25. Solubility was
      regulated by varying the ratio of less-soluble HA and more-soluble beta-TCP.
      After removal of stromal cells by pronase E treatment, ceramic surfaces were
      observed by scanning electron microscopy. Osteoclasts resorbed BCP most
      extensively, with an HA/beta-TCP ratio of 25/75, producing typical lobulated, zig
      zag track-like resorption lacunae. On pure beta-TCP, which had the highest
      solubility in acid, osteoclasts formed smaller discontinuous island-like lacunae.
      The resorption pattern may have been modified by the large number of calcium ions
      released into the acidic microenvironment at the osteoclast-ceramic interface. No
      resorption lacunae were found on the other specimens. The extent of osteoclastic
      resorption of calcium phosphate ceramics might, to a certain degree, be
      proportional to solubility, although this was not the case when solubility was
      very high. It would appear that ceramic solubility influences osteoclast
      resorption activity.

PMID- 9239466
TI  - Atomic force microscopic study of the surface morphology of apatite films
      deposited by pulsed laser ablation.
AB  - Atomic force microscopy (AFM) has been used to study the surface morphology of
      apatite films deposited on metallic and polyethylene substrates by laser ablation
      using KrF and transversely excited atmospheric CO2 lasers. The films are found to
      consist of a smooth apatite coating with macroparticles scattered on the surface.
      A wide variety of macroparticles, differing in size, shape and roughness, were
      found and analysed employing the high spatial resolution of AFM (< 1 nm). We have
      investigated the correlation between the apatite film morphology and the
      deposition conditions. Of particular importance are laser fluence, gas pressure,
      the nature of the target and the substrate temperature. We have explained these
      dependencies on the basis of a theoretical model which includes evaporation and a
      cluster-type laser ablation mechanism.

PMID- 9239467
TI  - In vitro inhibition of caries around a resin composite restoration containing
      antibacterial filler.
AB  - Class V cavities were prepared and restored with resin composite containing
      antibacterial filler powder (Apacider-AW, Ap-AW) using experimental restorations.
      The restored teeth were incubated in vitro with the cariogenic bacteria
      Streptococcus mutans IFO 13955. Ground sections were then prepared and examined
      using macrophotography. Lesions of the outer and inner wall were noted, and the
      depths of which the lesions penetrated were measured. We found that, in
      restorations containing 1-5 wt% Ap-AW, caries penetrated the marginal area, while
      in restorations containing 10 wt% Ap-AW the margin remained free of caries out to
      a distance of about 1.1 and 1.8 mm on the occlusal and gingival sides,
      respectively.

PMID- 9239468
TI  - Cell and soft tissue interactions with methyl- and hydroxyl-terminated alkane
      thiols on gold surfaces.
AB  - In order to evaluate the biological response induced by true methyl and hydroxyl
      surfaces, alkane thiols were immobilized onto gold. Initial protein adsorption
      from human plasma was measured in vitro by ellipsometry-antibody techniques and
      in vivo surface-cell interactions were evaluated in rat subcutaneous tissues for
      time periods ranging between 1 and 28 days. Rat mononuclear cells were studied
      after culturing (24 h) on the surfaces. Plasma protein experiments revealed
      deposition of fibrinogen onto the pure gold and the methylated surface. The
      hydroxylated surface tended to release the surface-associated proteins tested for
      by antibodies. None of the in vivolin vitro models used showed differences
      between the hydroxyl and methyl surfaces for spontaneous or augmented cell
      hydrogen peroxide and interleukin-1 alpha secretions. However, the different
      surface chemistries markedly affected the distribution of the cells that were
      recruited to the interfaces (cells in the fluid space and surface-associated DNA
      content on the retrieved implants) at late and early time periods. The results
      indicate that different implant surface properties, such as chemical
      functionality and hydrophobicity, influence specific events in the inflammatory
      cell response, and ultimately the wound healing around implantable materials.

PMID- 9239470
TI  - Epidemiology of prostate cancer and bladder cancer: an overview.

PMID- 9239469
TI  - Silicone rubber-hydrogel composites as polymeric biomaterials. IX. Composites
      containing powdery polyacrylamide hydrogel.
AB  - A composite material has been prepared consisting of a silicone rubber matrix and
      particulate lightly cross-linked polyacrylamide hydrogel. The material,
      resembling common silicone rubber, is hydrophilic and swells in water like
      hydrogels. The polyacrylamide has a high specific surface area, a relatively low
      content of water-soluble low-molecular-weight compounds and, owing to its non
      ionogenic character, a pH-independent swelling degree. For the composite material
      consisting of the silicone rubber and very fine powdery cross-linked
      polyacrylamide, we have measured the rate of swelling in water, the mechanical
      properties (tensile strength, break elongation, hardness, resilience), biological
      properties (implantation test, cytotoxicity, cell cultivation) and UV absorption
      of its water extracts. The polyacrylamide and polysiloxane purity, as the
      composite material starting components, has been determined to be satisfactory.
      As a result, a high swelling rate of the prepared composite material has been
      observed, resulting in reaching more than 70% wt of water of the equilibrium
      swelling. The results show that the composite material is suitable for biological
      and medical use.

PMID- 9239471
TI  - Von Hippel-Lindau syndrome: hereditary cancer arising from inherited mutations of
      the VHL tumor suppressor gene.

PMID- 9239472
TI  - New pathologic techniques for diagnosing genitourinary malignancies.

PMID- 9239473
TI  - Reverse transcriptase- polymerase chain reaction (RT-PCR) to detect prostate
      cancer micrometastasis in the blood.

PMID- 9239474
TI  - Successful separation between benign prostatic hyperplasia and prostate cancer by
      measurement of free and complexed PSA.

PMID- 9239475
TI  - Retroperitoneal lymphadenectomy in staging and treatment of clinical stage I and
      II nonseminomatous testis cancer (NSGCT): the development of nerve-sparing
      techniques.

PMID- 9239476
TI  - Current therapy for invasive bladder cancer.

PMID- 9239478
TI  - Three-dimensional conformal therapy (3D-CRT) for prostate cancer.

PMID- 9239477
TI  - Beyond the nerve-sparing radical prostatectomy.

PMID- 9239479
TI  - Cryosurgical ablation of the prostate: treatment alternative for localized
      prostate cancer.

PMID- 9239480
TI  - The chemoprevention of prostate cancer and the Prostate Cancer Prevention Trial.

PMID- 9239481
TI  - Total androgen blockade for prostate cancer: the end does not justify the means.

PMID- 9239482
TI  - Therapy for hormone-resistant prostate cancer: no longer a myth.
AB  - In conclusion, there have been impressive efforts to identify new cellular
      targets for the treatment of hormone-refractory disease. It appears that in some
      cases, survival may be extended; however, further prospective trials are
      necessary to confirm these observations.

PMID- 9239483
TI  - Renal, bladder, and prostate cancers: gene therapy.

PMID- 9239485
TI  - Assessing health-related quality of life in patients with genitourinary
      malignancies.

PMID- 9239484
TI  - The role of immunotherapy in urologic malignancies.

PMID- 9239486
TI  - Pulmonary aspiration.

PMID- 9239487
TI  - Antibiotics: what's new?

PMID- 9239488
TI  - Office management of encopresis.

PMID- 9239489
TI  - Emergency brain resuscitation.
AB  - With the discovery of new and effective acute stroke therapies, health care
      professionals now have the means to reverse the effects of an acute stroke. These
      advances must be aggressively applied to the acute stroke population using the
      EBR concept. It is clear from all of the issues and studies reviewed in this
      article that an organized approach and team concept are necessary for the
      efficient and effective care of acute stroke patients. Health care professionals
      currently treat acute myocardial infarction and trauma patients with a similar
      organization and sense of urgency. This paradigm should be translated and
      modified for the acute stroke population. Improved public and professional
      education are a vital part of this effort, and will have to be ongoing for its
      success. The approval of TPA as the first acute stroke therapy provides an
      opportunity to reverse the effects of a stroke. However, patients must present
      and be treated soon after stroke onset for this therapy to be safe and effective.

PMID- 9239490
TI  - Depression & anxiety in the primary care setting.
AB  - Depression and anxiety disorders are common in primary care. Diagnosis is
      accomplished by applying of specific, data-driven diagnostic criteria published
      in the DSM-IV. The differential diagnosis is sometimes difficult, but as a
      general rule the treatment of choice for both conditions is antidepressant
      medicine. It is very important to remember that anxiety disorders respond very
      nicely to most antidepressants, but depression does not respond to tranquilizers.
      BZs, should be reserved for adjunctive use in the early stages of treatment for
      both anxiety disorders and depression. The azapirone, buspirone, may be used as
      first line treatment for generalized anxiety disorder and may also augment
      antidepressants when the patient presents with mixed anxiety and depression. The
      important point is that when in doubt about either the diagnosis or which drug to
      choose first it is generally safe to select one of the newer antidepressants
      discussed in this article.

PMID- 9239491
TI  - The detection & management of deep venous thrombosis.
AB  - DVT is a serious health hazard that requires early detection and careful
      management. Noninvasive diagnostic testing provides an accurate method of
      diagnosis, which is especially useful in patients with easily identifiable risk
      factors. Noninvasive venous diagnostic testing used in an office practice is a
      safe and accurate method to determine the extent of venous disease. The tests
      should be done when significant risk factors, especially if multiple in number,
      for DVT are present.

PMID- 9239492
TI  - Management of advanced chronic obstructive pulmonary disease.
AB  - Successful Management of patients with advanced COPD includes not only a
      comprehensive therapeutic strategy tailored to the individual patient but also
      active patient participation. Figures 1 and 2 outline the medical and surgical
      treatment options for patients with advanced COPD. Patients who are actively
      smoking should be strongly advised to quit smoking. Bronchodilators and
      corticosteroids can improve symptoms and may prevent a further decline in lung
      function in selected COPD patients. The judicious use of antibiotics during an
      acute exacerbation may be required. O2 therapy improves survival and
      neuropsychiatric function in COPD patients with hypoxemia. Maintenance of proper
      nutrition is of utmost importance. A structured outpatient pulmonary
      rehabilitation is helpful in improving functional capacity and sense of
      breathlessness. In COPD patients who fail medical therapy, noninvasive positive
      pressure ventilation and surgical therapy may be considered.

PMID- 9239493
TI  - The biochemistry of cancer dissemination.
AB  - The progression of a tumor cell from one of benign delimited proliferation to
      invasive and metastatic growth is the major cause of poor clinical outcome of
      cancer patients. Recent research has revealed that this complex process requires
      many components for successful dissemination and growth of the tumor cell at
      secondary sites. These include angiogenesis, enhanced extracellular matrix
      degradation via tumor and host-secreted proteases, tumor cell migration, and
      modulation of tumor cell adhesion. Each individual component is multifaceted and
      is discussed within this review with respect to historical and recent findings.
      The identification of components and their interrelationship have yielded new
      therapeutic targets leading to the development of agents that may prove effective
      in the treatment of cancer and its metastatic progression.

PMID- 9239494
TI  - Investigation of nosocomial infection caused by arbekacin-resistant, methicillin
      resistant Staphylococcus aureus.
AB  - An outbreak of coagulase VII-producing, arbekacin (ABK)-resistant, methicillin
      resistant Staphylococcus aureus (MRSA) occurred between September 1994 and
      December 1995, involving five different wards. Twenty-one patients developed
      skin, wound, drainage, or respiratory tract colonization with coagulase VII
      producing, (ABK)-resistant MRSA. Phenotypic characteristics (production of
      enterotoxin and TSST-1, antimicrobial susceptibility) and molecular-typing
      procedure (plasmid DNA profile, pulsed-field gel electrophoresis [PFGE] and
      arbitrarily primed polymerase chain reaction [AP-PCR] of chromosomal DNA) in
      isolated strains were compared. Plasmid analysis identified four different
      profiles and 19 of 22 strains recovered had identical patterns. PFGE of
      chromosomal DNA identified three different subtypes and 18 (81.8%) isolates
      shared the same subtype. AP-PCR also demonstrated that most strains had the same
      phenotypic characteristics. Although traditional epidemiological methods; for
      example, coagulase typing, plays a central role in hospital infection control,
      combination of plasmid DNA profile, AP-PCR, and PFGE may prove to be a
      particularly informative means of tracking the nosocomial spread of MRSA.

PMID- 9239495
TI  - Verification of a PCR-based typing method for Acinetobacter baumannii in a pseudo
      outbreak investigation.
AB  - Acinetobacter spp. isolates were increasingly obtained from clinical specimens
      and sterility samples, and a subsequent epidemiological investigation implicated
      an intermittently contaminated supply of commercially acquired enrichment broths.
      Typing was performed with DNA amplification by the polymerase chain reaction
      (PCR) using enterobacterial repetitive intergenic consensus sequence primers,
      ERIC2 and reverse ERIC1R. The reliability of this PCR-based typing method was
      verified by the ability of the technique to demonstrate homology and differences
      among isolates from an epidemiologically well-defined pseudo-outbreak.

PMID- 9239496
TI  - Evaluation of growth characteristics on blood agar and eosin methylene blue agar
      for the identification of Candida (Torulopsis) glabrata.
AB  - Candida albicans and Candida (Torulopsis) glabrata are the most common species of
      yeast encountered in the clinical laboratory. In this study, we sought to
      evaluate simple means of screening cultures for the presence or absence of C.
      glabrata. Twelve thousand five hundred (12,500) consecutive cultures were
      evaluated for sufficient yeast growth to warrant identification. When detected
      (369 isolates), the amount of growth on eosin methylene blue agar (EMB) versus
      sheep blood agar (BAP) (both incubated in 5% CO2), wet mount morphology, and germ
      tube production were evaluated. All germ tube-negative yeasts were definitively
      identified using the Vitek YBC card. Of the 369 yeast isolates included in this
      study, 225 were C. albicans, 102 C. glabrata, and 42 other Candida species.
      Growth on EMB was greater than BAP for 92 isolates; all identified as C.
      glabrata. When EMB growth was equal to or less than BAP, 10 isolates were C.
      glabrata and 267 were other Candida ssp. An accurate presumptive identification
      of C. glabrata may be made using the observation of greater growth on EMB versus
      BAP. When coupled with the germ tube test, the majority of yeast isolates could
      be identified by these simple methods in our laboratory.

PMID- 9239497
TI  - A comparison of the Bactec 9000MB system and the Septi-Chek AFB system for the
      detection of mycobacteria.
AB  - The Bactec MB9000 (MB) continuous monitoring system was compared to the Septic
      Chek AFB (SC) for the detection of Mycobacterium species from all patient
      sources. A total of 1485 specimens were evaluated. Two hundred forty-eight
      specimens grew mycobacteria in one or both systems. The isolates recovered were
      18 Mycobacterium tuberculosis (MTB), 109 M. avium complex (MAC), 59 M. fortuitum
      chelonae complex (MFC), 51 pigmented mycobacteria (PGM), and 11 nonpigmented
      mycobacteria, not MTB/MAC (NP). Of the 248 positive specimens, 157 were positive
      in both systems; 73 in the SC only; and 18 in the MB only. The mean times to
      detection for specimens were 11.5 days for MB versus 16.4 days for SC. The false
      positivity rate in the MB was 5.8%. Contamination rates for the MB and the SC
      were 12.7% and 19.8%, respectively. These data suggest that the automated MB
      system has clear advantages over the manual SC system in terms of earlier time to
      detection of significant mycobacteria, less technical hands-on time, and a lower
      contamination rate.

PMID- 9239498
TI  - Evaluation of a commercial polymerase chain reaction assay for the detection of
      Chlamydia trachomatis.
AB  - Cell culture has traditionally been considered the most sensitive method for
      detecting Chlamydia trachomatis from clinical specimens, but depends upon the
      organisms being viable at the time of cell inoculation. Furthermore, cell culture
      is slow and labor intensive. Even when a special transport medium is used, there
      is a progressive loss of viability of C. trachomatis during transport. The
      detection of C. trachomatis by cell culture is more rapid when immunofluorescence
      is used to detect early antigen, but requires considerable experience to
      interpret. The Amplicor C. trachomatis system is a commercial polymerase chain
      reaction (PCR)-based assay combined with nucleic acid hybridization for the
      direct detection of C. trachomatis in urine and swabs of appropriate sites, with
      results available within 6 h. All specimens for C. trachomatis received by the
      Royal Perth Hospital Department of Microbiology during the period 1 July 1994 to
      30 June 1995 that were suitable for culture and Amplicor PCR were tested by both
      methods (2029 specimens). Discordant results were obtained in nine cases and
      resolved by additional testing. Seventy-one specimens were confirmed as true
      positives, of these Amplicor PCR correctly detected 67 (sensitivity 94.4%) and
      culture correctly detected 62 (sensitivity 87.3%). The Amplicor PCR assay was
      found to be more sensitive and as specific as culture. It had the added
      advantages of ease of use, rapid availability of results, standardization and was
      more suited than culture to processing large number of specimens.

PMID- 9239499
TI  - Imipenem and meropenem activity against mecA-positive homogeneously and
      heterogeneously oxacillin-resistant and mecA-negative oxacillin-borderline
      susceptible staphylococci.
AB  - Microbroth dilution and disk-diffusion testing of imipenem and meropenem was
      performed at 35 and 30 degrees C against 61 phenotypic expression class 3,4 and 9
      phenotypic expression class 1,2 oxacillin-resistant isolates of Staphylococcus
      aureus (ORSA), 51 oxacillin-borderline-susceptible isolates of S. aureus (BORSA),
      and 37 phenotypic expression class 3,4 and 9 phenotypic expression class 1,2
      isolates of Staphylococcus epidermidis (ORSE). Imipenem MIC ranges at 35 degree C
      were 0.6 to > 64 micrograms/ml for class 3,4 ORSA, 0.03 to 0.25 micrograms/ml for
      class 1,2 ORSA, 0.015 to 0.12 micrograms/ml for BORSA, 0.03 to 64 micrograms/ml
      for class 3,4 ORSE, and 0.12 to 8 micrograms/ml for class 1,2 ORSE. Corresponding
      values for meropenem were 0.5 to 64 micrograms/ml, 0.12 to 4 micrograms/ml, 0.06
      to 1 microgram/ml, 0.5 to 64 micrograms/ml, and 1 to 8 microgram/ml. MIC ranges
      at 30 degrees C did not differ by more than 1 log2 dilution from those at 35
      degrees C. After 24 h incubation of disk-diffusion tests at 35 degrees C, 44% of
      class 3,4 and 100% of class 1,2 ORSA isolates were imipenem-susceptible; after an
      additional 24 h at 25 degrees C, 39 and 100% of these isolates, respectively,
      remained susceptible to imipenem. Similar values were obtained with 24 h
      incubation at 30 degrees C followed by 24 h at 25 degrees C. All BORSA isolates
      were susceptible to imipenem. Of the ORSE isolates, 22 and 78% of isolates in
      classes 3,4 and 1,2, respectively, were susceptible at 24 h with little change
      after an additional 24 h at 25 degrees C. Similar trends were observed with
      meropenem. In parallel disk-diffusion studies with oxacillin, false
      susceptibility rates of 5% of class 3,4 and 44% class 1,2 ORSA isolates after 24
      h of incubation at 35 degrees C were reduced to 3 and 0%, respectively, after an
      additional 24 h of incubation at 25 degrees C. Imipenem- and meropenem-resistant
      subpopulations of oxacillin-resistant staphylococci did not seem to be detected
      by altered susceptibility testing conditions.

PMID- 9239500
TI  - Evaluation of the in vitro activity of cefepime compared to other broad-spectrum
      cephalosporins against clinical isolates from eighteen Brazilian hospitals by
      using the Etest.
AB  - The in vitro activity of cefepime was compared to that of ceftazidime,
      ceftriaxone, and cefotaxime in a multicenter study involving 10 clinical
      microbiology laboratories and clinical isolates from 18 Brazilian hospitals from
      7 cities (4 states). A total of 982 isolates consecutively collected between
      December 1995 and March 1996 were susceptibility tested by using Etest and
      following the NCCLS procedures for agar diffusion tests. The cefepime spectrum
      was broader than that of the other broad-spectrum cephalosporins against both
      Gram-negative rods and Gram-positive cocci. Cefepime was particularly more active
      against Enterobacter sp. (MIC90, 2 micrograms/ml), Serratia sp. (MIC90, 2
      micrograms/ml) and oxacillin-susceptible Staphylococcus aureus (MIC90, 3
      micrograms/ml). Against Pseudomonas aeruginosa, cefepime (MIC90, 16
      micrograms/ml) was slightly more active than ceftazidime (MIC90, 32
      micrograms/ml) and 8- to 16-fold more active than ceftriaxone of cefotaxime
      (MIC90, > 256 micrograms/ml). Our results show that nosocomial bacteria,
      especially Gram-negative rods, have a high rate of cephalosporin resistance in
      Brazil. However, part of these resistant bacteria remains susceptible to
      cefepime. The Etest was shown to be an excellent method for multicenter studies
      of the in vitro evaluation of new antimicrobial agents.

PMID- 9239502
TI  - Accuracy of the Vitek system for antimicrobial susceptibility testing
      Enterobacteriaceae bloodstream infection isolates: use of "direct" inoculation
      from Bactec 9240 blood culture bottles.
AB  - A recent investigation indicates that rapid antimicrobial susceptibility tests
      (AST) can affect patient therapy leading to reductions in health-care costs for
      some patient populations. However, there is little information relative to the
      often performed direct inoculation of positive blood culture bottles into rapid
      AST systems. AST results of direct inoculated Vitek (bioMerieux Vitek, Hazelwood,
      MO, USA) GNS cards were compared to those inoculated per package insert
      recommendations and a reference broth microdilution test using 50 consecutive
      Enterobacteriaceae bloodstream infection isolates. Escherichia coli (44% of
      isolates), Klebsiella ssp. (30%), and six other members of this family were
      tested against 15 antimicrobial agents. The direct inoculation method produced
      only two false-susceptible (0.3%), seven false-resistant (0.9%; six different
      drugs), and 48 minor errors (6.4%). The GNS cards inoculated in the usual,
      recommended manner had no very major error, and 7.5% combined major and minor
      errors. If the results of the urinary infection-specific drugs (nitrofurantoin,
      trimethoprim/sulfamethoxazole; not appropriate for bacteremia therapy) and
      ampicillin/sulbactam were deleted, both Vitek inoculation methods yielded results
      well within acceptable limits (< or = 4.5% overall error). These results indicate
      that the direct inoculation method of Vitek GNS cards from Enterobacteriaceae
      bloodstream infections (detected by Bactec 9240, Becton-Dickinson, Cockeysville,
      MD, USA) performed as well as the NCCLS broth microdilution test. Thus, a
      procedural modification of this type could further accelerate rapid access to
      accurate AST data.

PMID- 9239501
TI  - In vitro antimicrobial activity of RU-59863, a C-7 catechol substituted
      cephalosporin.
AB  - The in vitro activity of RU-59863, a so-called "fifth generation" catechol
      cephalosporin, was evaluated against 606 bacterial isolates and compared with the
      activities of cefotaxime, ceftazidime, cefepime, and cefpirome. RU-59863
      demonstrated a broad spectrum of inhibition and superior overall activity than
      comparators when tested against Enterobacteriaciae (MIC90s, 0.015 to 2
      micrograms/ml), Pseudomonas aeruginosa (MIC90, 0.5 microgram/ml),
      Stenotrophomonas maltophilia (MIC90, 0.25 microgram/ml), Acinetobacter ssp.
      (MIC90, 4 micrograms/ml), and oxacillin-susceptible Staphylococcus ssp. (MIC90s,
      0.5 to 8 micrograms/ml). Potent RU-59863 activity was also observed against beta
      haemolytic and viridans gr. streptococci (MIC90s, 0.12-0.5 microgram/ml),
      Streptococcus pneumoniae (MIC90s, 0.03 to 0.5 microgram/ml), Haemophilus
      influenzae (MIC90, 0.06 microgram/ml), and Neisseria gonorrhoeae (MIC90, 0.06
      micrograms/ml). RU-59863 demonstrated marginal potency against Enterococcus
      faecalis (MICs 2 to 16 micrograms/ml) and was inactive against Enterococcus
      faecium (MIC90, > 128 micrograms/ml). Oxacillin-resistant staphylococci were not
      inhibited by RU-59863 (MIC90s, 32 to 128 micrograms/ml). Among the cephalosporins
      tested, RU-59863 performed best versus ceftazidime-resistant Bush group 1
      isolates and strains producing extended spectrum beta-lactamases. RU-59863 was
      also effective against many fluoroquinolone-, aminoglycoside-, and imipenem
      resistant isolates. RU-59863 seems to be a significant advance in cephalosporin
      chemistry and activity, especially against Gram-negative pathogens resistant to
      current beta-lactam therapeutic agents. Further studies of human pharmacokinetics
      and against clinical infections are encouraged.

PMID- 9239503
TI  - Is cellulose acetate electrophoresis a suitable technique for detection of Hb
      Bart's at birth?
AB  - Symptomatic alpha-thalassemia (alpha-thal) as found in South-East Asia is
      uncommon in India. However, the presence of Hb Bart's in cord blood samples has
      been reported from different parts of India and the prevalence of alpha-thal has
      ranged from 0.5 to 18% by different electrophoretic techniques. The methodology
      utilised has ranged from paper electrophoresis to isoelectric focussing (IEF). We
      screened 798 cord bloods for the presence of Hb Bart's by cellulose acetate
      electrophoresis and found a prevalence rate of alpha-thal of 15.3% in a
      heterogenous population in Bombay. A comparison of four different electrophoretic
      techniques for detection of Hb Bart's in 138 neonates showed that cellulose
      acetate and starch gel electrophoresis were by and large comparable and only a
      little less sensitive than IEF. Paper electrophoresis used at many centers in
      India was most insensitive. As alpha-genotyping is not possible at most centers
      in the country, it is suggested that a simple cellulose acetate electrophoresis
      would be the method of choice for screening neonates for alpha-thal in India. As
      a part of our follow-up study, alpha-genotyping was done by Southern blot
      hybridization in 24 cases who had shown variable levels of Hb Bart's at birth.
      The rightward deletion (-alpha3.7/) either in a heterozygous or homozygous
      condition was the only gene defect encountered in this preliminary study.
      However, 7 of 24 cases (29.17%) showed no correlation between Hb Bart's level and
      alpha-genotypes.

PMID- 9239504
TI  - Ethnic differences in interferon-alpha allele frequencies.
AB  - Interferon-alpha (IFN-alpha) is a protein family controlled by altogether 26
      different IFN-alpha genes. We have previously described an SspI polymorphism in
      the IFN A17 gene and an association between the SspI A2 allele and nasopharyngeal
      cancer. In this paper we present data on ethnic differences with respect to IFN
      A17 SspI allele frequencies. Thus the frequency of the SspI A1 allele was high in
      two different Chinese populations (51 and 48%, respectively) and much lower (11%)
      in Swedes. Intermediate values were found in African Blacks (32%), Indians (25%),
      Saamis (29%) and Finns (24%). The very pronounced differences between major
      ethnic groups make the IFN A17 SspI polymorphism a very informative
      anthropological marker system and suggest that it may be balanced and maintained
      by natural selection.

PMID- 9239506
TI  - A faster and more general hidden Markov model algorithm for multipoint likelihood
      calculations.
AB  - There are two basic algorithms for calculating multipoint linkage likelihoods: in
      one the computational effort increases linearly with the number of pedigree
      members and exponentially with the number of markers, in the other the effort
      increases exponentially with the number of persons but linearly with the number
      of markers. We describe a faster version of the latter algorithm for which there
      is no penalty in making the recombination fraction meiosis specific. This can
      lead to faster and potentially more powerful linkage analysis whenever the number
      of nonfounder meioses in a pedigree is not too large.

PMID- 9239505
TI  - Allele frequencies for 20 microsatellites in a worldwide population survey.
AB  - 20 microsatellite polymorphisms: HUMHPRT, HUMD3S1358, HUMTH01, HUMACPP, HUMVWF,
      HUMD16S310, HUMD4S243, HUMTPO, HUMFES/FPS, HUMF13A1, HUMDHFRP2, HUMD11S2010,
      HUMD13S767, HUMD9S926, HUMD2S1328, HUMD14S306, HUMD18S848, HUMD5S818, HUMD7S820
      and HUMFGA were analyzed in a worldwide survey covering five continents and
      allele frequencies are given. There is a high heterogeneity in allele frequencies
      among continents. A neighbor-joining tree based on Fst distance shows a pattern
      of differentiation that may reflect the role of drift in the development of
      genetic differences among humans. The variation found between continents confirms
      the usefulness of tetranucleotide microsatellites in human genetic variation
      studies.

PMID- 9239508
TI  - Linkage analyses in type I diabetes mellitus using CASPAR, a software and
      statistical program for conditional analysis of polygenic diseases.
AB  - We have developed software and statistical tools for linkage analysis of
      polygenic diseases. We use type I diabetes mellitus (insulin-dependent diabetes
      mellitus, IDDM) as our model system. Two susceptibility loci (IDDM1 on 6p21 and
      IDDM2 on 11p15) are well established, and recent genome searches suggest the
      existence of other susceptibility loci. We have implemented CASPAR, a software
      tool that makes it possible to test for linkage quickly and efficiently using
      multiple polymorphic DNA markers simultaneously in nuclear families consisting of
      two unaffected parents and a pair of affected siblings (ASP). We use a simulation
      based method to determine whether lod scores from a collection of ASP tests are
      significant. We test our new software and statistical tools to assess linkage of
      IDDM5 and IDDM7 conditioned on analyses with 1 or 2 other unlinked type I
      diabetes susceptibility loci. The results from the CASPAR analysis suggest that
      conditioning of IDDM5 on IDDM1 and IDDM4, and of IDDM7 on IDDM1 and IDDM2
      provides significant benefits for the genetic analysis of polygenic loci.

PMID- 9239507
TI  - Genetic polymorphism of AHSG, FXIIIB, HP and PLG serum proteins in six Jewish
      groups in Israel.
AB  - The allelic distribution of the polymorphic serum proteins AHSG, PLG, FXIIIB and
      HP was studied in six Jewish groups who migrated to Israel from the Middle East,
      North Africa, Rumania, Bulgaria, Central and Eastern Europe. The observed AHSG
      and PLG allele frequencies in these Jewish groups were more or less similar to
      the observed distributions in non-Jewish populations from their respective areas
      of origin, while FXIIIB and HP frequencies were similar to those in European
      populations. Therefore, no uniform pattern of genetic relationships between the
      Jewish groups was observed. A genetic distance analysis including comparative
      data from Europe and the Middle East reflected differences between the Jewish
      groups according to their areas of origin.

PMID- 9239509
TI  - Linkage analysis under locus heterogeneity: behaviour of the A-test in complex
      analyses.
AB  - The admixture test (A-test) is a popular method for the analysis of linkage data
      when locus heterogeneity is suspected. It can be applied on pairwise linkage
      data, multipoint data and even for the simultaneous analysis of data from
      multiple dispersed candidate regions. However, very little is known about the
      conditions for the use of the method under these divergent circumstances. By
      performing analytical evaluations, we demonstrate that the A-test is inconsistent
      if there is a relationship between the phenotype and the probability of being
      linked. Biased estimates of the recombination fraction (theta) and the proportion
      of linked families (alpha) may occur if the actual frequency of linked families
      is not identical among small and large families. We conclude that the A-test
      should be used with caution if the phenotype and the probability of developing
      the phenotype at a certain age cannot be shown to be equal for family members of
      linked and unlinked families. If dissimilarities in family size cannot be ruled
      out, the extent of bias should be considered and size specific alpha-values
      should be used in risk calculations.

PMID- 9239510
TI  - A novel missense mutation D676N in the plasminogen gene causes loss of functional
      activity.

PMID- 9239511
TI  - Mapping using linkage disequilibrium estimates: a comparative study.

PMID- 9239512
TI  - Paracrine stimulation of keratinocytes in vitro and continuous delivery of
      epidermal growth factor to wounds in vivo by genetically modified fibroblasts
      transfected with a novel chimeric construct.
AB  - BACKGROUND: Growth factors play an important role in tissue repair. While the
      effectiveness of growth factor therapy in animal wound healing models and limited
      human clinical trials has been demonstrated, the ideal method for their
      administration to the wound remains unclear. Experimental data suggest that the
      continuous presence in the early stages of wound repair is beneficial. MATERIALS
      AND METHODS: We have constructed a novel chimeric expression plasmid in which the
      biologically active portion of the human epidermal growth factor (EGF) gene is
      fused in-frame to the human granulocyte colony-stimulating factor signal
      sequence. RESULTS: Clonally selected human fibroblasts transfected with this
      construct secrete biologically active EGF. After the transplantation of
      irradiated gene-transfected fibroblasts suspended in fibrin glue to murine full
      thickness wounds, EGF can be demonstrated for at least seven days in the wounds,
      slowly decreasing from initially 470 pg/ml to 140 pg/ml on day 7. No EGF was
      found in the wound at day 14. CONCLUSIONS: A single application of irradiated EGF
      genetransfected fibroblasts to wounds can thus continuously deliver the transgene
      in vivo and could be used to administer drugs to the wound bed during the crucial
      first seven days of wound-healing.

PMID- 9239513
TI  - Characterizing human colorectal carcinomas by proteolytic profile.
AB  - Clinicopathologic staging of colorectal cancers cannot always predict
      aggressiveness of prognosis for a particular patient. We have used activity
      assays for cysteine proteinases, cathepsins B, L and H (CB, CL and CH) and matrix
      metalloproteinases, MMP-2 and MMP-9, to identify several distinctive,
      reproducible proteolytic profiles in a large set of colorectal carcinomas. We
      observed that individual proteinases demonstrated specific and distinct levels of
      activity at different cancer stages, possible reflecting non-random steps in a
      proteolytic cascade related to tumor development. We also observed that
      individual colon cancers fell into relatively few categories when characterized
      for the combined expression of three proteinases: CB, CL and MMP-9. Four
      proteolytic profiles, designated "Early", "Middle", "Late", and "High", could be
      used to define almost 80% of the colorectal carcinomas analyzed. Such profiles,
      based on the expression of several proteinases in a given tumor, provided
      information independent of clinical stage and may identify crucial variations in
      tumor behavior.

PMID- 9239514
TI  - Reversal of cisplatin resistance in vivo by an anti-fos ribozyme.
AB  - Human colon cancer cells, SW480DDP and SW620DDP, which express fos gene highly,
      are resistant to cisplatin treatment. We prepared a hammerhead ribozyme to
      selectively cleave fos mRNA and revealed that the for ribozyme significantly
      suppressed the expression of fos gene in resistant cells in vitro. The fos
      ribozyme which was transfected into the implanted tumor cells resistant to
      cisplatin, had also the ability to reduce the expression of fos gene in vivo, and
      reversed cell sensitivity to cisplatin. These results reinforce the potential
      role of anti-oncogene ribozymes in dealing with the problem of drug resistance,
      with new possible implications for gene targeting therapy.

PMID- 9239515
TI  - Acute effects of static magnetic fields on cutaneous microcirculation in rabbits.
AB  - The acute microcirculatory effects of locally applied of static magnetic (SMF) to
      the cutaneous tissue within a rabbit ear chamber (REC) were evaluated during
      consciousness. Rabbits with REC were subjected to microphotoelectric
      plethysmography. Power levels of SMF upon the REC were controlled at 1, 5, 10
      mT(milli Tesla), respectively. The duration of exposure was 10 minutes. The
      exposure of SMF induced variation of vasomotion with a latency of about 10
      seconds in a non-dose dependent manner. SMF had a biphasic effect upon the
      microcirculatory system; when the vascular tone was low, the SMF enhanced
      vasomotion, and when it was high, the SMF suppressed vasomotion. The results
      suggest that the SMF can modulate vascular tone due to vasomotion which may
      involve in clinical efficacy for refraining from neck and shoulder stiffness.

PMID- 9239516
TI  - Lack of carcinogenesis by the baked mushroom Agaricus bisporus in mice: different
      feeding regimen [corrected].
AB  - Agaricus bisporus, the cultivated mushroom of the western hemisphere, was baked
      at 220-230 degrees C for 10 minutes and subsequently fed to mice for 12 hours
      each day, five days each week throughout their life. After each feeding cycle,
      the animals received a well-balanced semisynthetic diet for 12 hours each day for
      five days plus the remaining two full days each week. The estimated average daily
      mushroom consumption per animal was 4.8 g for a female and 4.2 g for a male.
      Randomly bred Swiss mice, six weeks old at the start of the experiment, were
      used. In the baked mushroom-fed group, the incidences of tumors in the lungs,
      blood vessels, cecum, and colon increased when compared to the untreated
      controls. These increases were not, however, statistically significant. In
      another previous experiment, both the raw and the baked mushrooms, when used in
      different feeding regimens, induced statistically significant incidences of
      cancers in several organs of the mice. It is possible that the negative finding
      in the current study was due to insufficient mushroom consumption.

PMID- 9239517
TI  - Positive interaction of bisbenzylisoquinoline alkaloid, cepharanthin, with vinca
      alkaloid agents against human tumors.
AB  - Cepharanthin (CE), a bisbenzylisoquinoline alkaloid drug, was tested in vitro and
      in vivo with chemotherapeutic agents, vincristine (VCR), vinblastine (VLB), and
      vindesine (VDS). The activity of these agents alone or in combination was tested
      against a human colon cancer cell line (RPMI 4788) or a human uterine cervical
      cancer cell line (HeLa), using a modified microcytotoxicity-viable cell staining
      assay. In the in vitro study, the antiproliferative activities of each vinca
      alkaloid were enhanced additively or synergistically by combination with CE in
      RPMI 4788 cells as well as HeLa cells. The sequential exposure of the RPMI 4788
      cells or HeLa cells to both CE and each vinca alkaloid agent showed evidence of a
      more significant potentiation. The antiproliferative activity of the combination
      of each vinca alkaloid agent(VCR, VLB, or VDS) with CE was almost equivalent to
      the effect of each vinca alkaloid agent alone which was potentiated by CE tenfold
      through several hundredfold. In an experimental model of tumor growth and
      survival, in which RPMI 4788 cells were transplanted subcutaneously or
      intraperitoneally into BALB/c nu/nu mice respectively, CE (1 mg/kg) alone exerted
      not significant inhibitory activity against tumor growth or survival, and VCR
      (0.25 mg/kg) alone partially inhibited these antitumor activities. Furthermore,
      the antitumor effects of VCR were elevated synergistically by the simultaneous
      administration of CE. These studies indicate that due to their therapeutic
      potential, combinations of vinca alkaloid agent with CE might be a promising
      therapy for some human cancers.

PMID- 9239519
TI  - Granulosa cell kinetics examined by bromodeoxyuridine in combination with
      colchicine in the mouse ovarian follicles.
AB  - To elucidate the relationship between follicular growth and granulosa cell
      kinetics, ovarian histology was examined in mice treated with 5-bromo-2'
      deoxyuridine (BrdU) or in combination with colchicine. In normal-cycling mice,
      active proliferation of the granulosa cells started in some follicles with
      diameters of more than 30 microns and all follicles more than 70 microns in
      diameter had already grown. Thus follicles between 30 and 70 microns were
      selected to start growing from those remaining in the resting phase. Although the
      granulosa cells synthesize DNA and mitosis took place throughout the epithelia in
      the follicles < 300 microns, such proliferating cells were distributed
      centripetally in follicles > 300 microns. In follicles measuring more than 400
      microns in diameter DNA synthesis and cell division occurred in the inner
      epithelial layers after which, some of the divided cells moved to the outermost
      mural layer as fully differentiated cells to prepare for ovulation.

PMID- 9239518
TI  - Cell proliferation in aortic, mammary artery and saphenous vein biopsies in
      patients subjected to open heart surgery.
AB  - BACKGROUND: Stenosis of venous vascular grafts is a common phenomenon after
      coronary by-pass surgery and the factors related to stenosis are not completely
      understood. Cell proliferation in vascular channels is one of the features
      related to occlusion. This study is a prospective clinicopathological study of
      the relationship between cell proliferation and clinical factors in patients
      suffering from atherosclerotic heart disease. Materials. The expression of cell
      proliferation related protein Ki-67 was analyzed in samples obtained from aortic
      wall, internal mammary artery, and saphenous vein in 96 patients subjected to
      open heart surgery. METHODS: The expression of Ki-67 in vascular channel intima
      and media was analyzed by immunohistochemical techniques. The results of Ki-67
      immunolabelling were compared to clinical features and to the medical therapy of
      the patients. RESULTS: Cell proliferation was higher in males than in females in
      the aortic wall (p = 0.05). The expression of Ki-67 was significantly higher (p =
      0.004) in venous intima in patients with insulin-dependent diabetes than in
      patients with non-insulin dependent diabetes or with no diabetes. CONCLUSIONS:
      The results show that variations in cell proliferation rates in vessel walls may
      be related to the potential risk of stenosis of vascular grafts particularly in
      patients with insulin-dependent diabetes mellitus.

PMID- 9239520
TI  - Intramural carcinomas of the uterine corpus: a clinicopathological study.
AB  - Cases in which no sizable amount of tumor was observed in the uterine cavity and
      the main foci of the carcinoma were exclusively confined to the myometrium, were
      studied pathologically in a series of carcinomas of the uterine corpus. Ten out
      of 350 carcinomas of the uterine corpus proper fell into this category, and one
      case of suspicious metastatic corpus tumor from the ovary was also considered.
      The growth pattern of these tumors was classified into following 6 groups: (a)
      growth confined to the myometrium, (b) nodular growth in the myometrium with
      minimal endometrial involvement, (c) scattered (scirrhous) growth in the
      myometrium with marked shedding of the endometrium, (d) almost complete
      replacement of the myometrium by carcinoma with endometrial shedding (e) extreme
      subtype of usual endophytic growth pattern and (f) diffuse, intra-lymphatic
      spread of secondary tumor. One, 2, 3, 1, 3, and 1 cases of tumors of group, (a)
      (f), were observed respectively in our pathological files. A spectrum of initial
      symptoms, diagnostic procedures, histology and histogenesis of the tumor was
      described in this report.

PMID- 9239521
TI  - Specific regulation of HSPs in human tumor cell lines by PSK.
AB  - Substantial progress has been make in elucidating the biochemical properties of
      HSPs (Heat Shock Proteins) as molecular chaperones in protein biogenesis and
      their roles in thermoprotection and cytoprotection against cellular insults.
      Recently, besides advantageous cellular functions, the detrimental role of HSPs
      has been implicated in a variety of diseases. HSP47 is assumed to be a collagen
      specific molecular chaperone and its involvement in the progression of fibrosis
      was observed. There have been a number of reports that suggest the role of HSP60
      as an autoantigen in a variety of autoimmune diseases. PSK, a protein-bound
      polysaccharide, is a biological response modifier that is clinically used for the
      treatment of cancer patients in Japan. PSK shows a broad range of biological
      effects in addition to the antitumor activity. In this study, we evaluated the
      effect of PSK on the expression of HSPs in human tumor strains at the protein and
      mRNA levels. PSK was observed to suppress the expression of HSP47 and HSP60 but
      not HSP72/73 in human tumor cell lines. Thus, the novel pharmacological potential
      of PSK was suggested in the diseases derived from the aberrant expression of
      HSPs.

PMID- 9239522
TI  - Specific regulation of HSPs in human tumor cell lines by flavonoids.
AB  - While the protective role HSPs (Heat Shock Proteins) has been recognized against
      physiological stress such as heat shock, heavy metals and glucose starvation,
      recent progress has revealed another aspect of HSPs in various diseases. HSP27
      has been shown to be involved in the acquired resistance of tumor cells
      hyperthermic and chemotherapeutic treatment. In human breast tumors,
      overexpression of HSP27 is associated with a shorter disease-free survival
      period. HSP47 is thought to be a collagen specific molecular chaperone. The
      involvement of HSP47 in the progression of fibrosis has been reported. Aberrant
      expression of HSP could cause various autoimmune diseases. Manipulation of HSP
      expression, therefore, could be a therapeutic target to reduce HSP-derived
      detrimental cellular effects. Flavonoids are a widely distributed group of plant
      substances, universally present in vascular plants. Although the flavonoids have
      been known as natural plant products as long as the alkaloids, their
      pharmacological effects and potential medicinal uses have been little studied by
      comparison. Today, the picture has changed and the biological and pharmacological
      activities of plant flavonoids look promising. We investigated the effect of
      flavonoids on the expression of HSPs in human tumor cell lines. Flavonoids
      inhibited the expression of HSP27, HSP47, HSP60 and HSP72/73. The results
      suggested the pharmacological possibilities of flavonoids in diseases derived
      from abnormal expression of HSPs.

PMID- 9239524
TI  - A model-based method for selecting an acceptable dose in phase IIa
      chemoprevention trials.
AB  - In a cancer chemoprevention trial, it is vitally important to use a dose that
      will limit intolerable side-effects. Unlike the situation with cancer drug
      treatment, the side-effects are relatively moderate, only rather low levels will
      be permitted, and the time to development of intolerability may be long and
      variable. These characteristics all argue in favor of a fixed-sample size, and a
      fixed-dose design. Here we give a very general procedure for selecting an
      acceptable dose for subsequent testing based on such a design. We also show how a
      simple program can display the characteristics of various designs graphically,
      permitting a common-sense selection.

PMID- 9239523
TI  - Gene expression of zinc-alpha 2-glycoprotein in normal human epidermal and buccal
      epithelia.
AB  - Zinc-alpha 2-glycoprotein (Zn alpha 2gp) is almost ubiquitous in body fluids. We
      have found it to be also present in stratified epithelia. We compare its mRNA
      expression in cells from human epidermis and buccal mucosa cultured in media of
      graded differentiation potential (attained by varying calcium ion concentration
      and adding serum). The Zn alpha 2gp gene is upregulated in both epithelia with
      differentiation and further with exposure to interferon gamma or transforming
      growth factor beta 1. The upregulation by these agents increases with
      differentiation in epidermal cells, but peaks in the low-differentiation medium
      in buccal epithelia. We compared gene expression levels of Zn alpha 2gp with
      those of characteristic cytokeratins of stratified epithelia (k5 for basal cells,
      K10 for epidermal suprabasal cells, and K13 for mucosal suprabasal cells). This
      pattern correlation associates Zn alpha 2gp cell-type dependently with late
      differentiation, i.e. with keratin K10 in epidermis and with K13 in buccal
      epithelium.

PMID- 9239525
TI  - Increased plasma bilirubin in Parkinson patients on L-dopa: evidence against the
      free radical hypothesis?
AB  - Oxidative damage by free radicals may contribute to the etiology of Parkinson's
      disease (PD), and increased oxidative stress in the nigral cells of PD patients
      may occur following L-dopa treatment, prompting suggestions that L-dopa therapy
      should be delayed as long as possible. Bilirubin is a potent antioxidant in
      vitro, even when bound to albumin, suggesting a physiological role as an
      antioxidant. Calculations indicate that bilirubin can pass the blood-brain
      barrier in sufficient quantity to exert a significant antioxidant effect in the
      brain. We have found a highly significant (about 20%) increase in plasma
      bilirubin in 162 PD patients on chronic L-dopa treatment compared to 93 untreated
      parkinsonians and 224 non-parkinsonian controls. We propose that L-dopa-induced
      increase in nigral oxidative stress in PD may be effectively counteracted by
      increased bilirubin levels. The mechanism by which plasma bilirubin is increased
      in patients receiving L-dopa is at present unknown.

PMID- 9239526
TI  - Paclitaxel neurotoxicity: clinical and neurophysiological study of 23 patients.
AB  - Paclitaxel is the prototype of a new class of chemotherapeutic agents with an
      antimitotic effect that is related to its ability to interfere with the
      microtubule system. It causes peripheral neurological toxicity by means of its
      activity on the axonal microtubules. To define the clinical and
      neurophysiological characteristics of paclitaxel neuropathy 23 patients
      undergoing paclitaxel therapy at a dose of 175 mg/m2 were studied. The patients
      were divided into two groups, with only one group receiving pretreatment with
      potentially neurotoxic drugs such as cisplatin and carboplatin. The results
      showed a high incidence of mild neurotoxicity in both groups. Treatment was
      discontinued due to severe neurotoxicity in only one patient pretreated with
      platinum-compounds. The clinical and neurophysiological data make it possible to
      define paclitaxel neurotoxicity as a distal axonal neuropathy with a summatory
      effect in patients pretreated with cisplatin; the possible reversibility of
      paclitaxel neurotoxicity requires further confirmation.

PMID- 9239527
TI  - Binocular interaction in normal vision studied by pattern-reversal visual evoked
      potential (PR-VEPS).
AB  - Monocular and binocular visual evoked potentials (VEPs) in response to different
      check size (15-21-38-84 minutes or arc) were studied in 14 subjects with normal
      visual acuity and stereopsis. The binocular VEP amplitude is slightly higher than
      the VEP amplitude on stimulation of the "better eye" and significantly higher
      than the VEP amplitude on stimulation of the "worse eye"; this effect is observed
      using small checks and almost exclusively involved N75-P100. Both the N75 and
      P100 peaks occur earlier after binocular than monocular stimulation. The
      shortening of the N75 mean latency is significantly greater than that of the P100
      mean latency when larger check sizes are used. The mean latency of the N145
      potential is not significantly different in monocular and binocular stimulus
      conditions. The slight summation effect and latency shortening in the binocular
      VEPs are not consistent with the hypothesis that it is the sum of separate
      monocular signals originating from the visual cortex that gives rise to the
      response. The early components of both monocular and binocular VEPs are thought
      to be of post-synaptic origin (outside layer 4c of area 17), where the inputs
      become mixed so that most cells receive information from both eyes. The amplitude
      enhancement of binocular VEPs, which mainly occurs when using small checks, may
      be related to the increase in the total amount of cortical activity representing
      the macular region; this may account for binocular superiority in fine spatial
      resolution. The latency shortening in binocular conditions can be explained by
      considering that the critical determinant of the latency is the fundamental
      spatial frequency of the pattern. When coarse patterns are used, their
      effectiveness in parafoveal stimulation may affect the VEPs, with a significant
      contribution coming from the more peripheral retina. The enlargement of the
      visual field when the eyes see simultaneously may therefore further reduce the
      latency of the response when using the larger checks suitable for eccentric
      stimulation.

PMID- 9239528
TI  - Lead, cadmium, and selenium in the blood of patients with sporadic amyotrophic
      lateral sclerosis.
AB  - We determined whole blood lead and cadmium levels, and serum selenium levels in
      patients with sporadic amyotrophic lateral sclerosis and age- and sex-matched
      controls. Disability due to the disease directly correlated with lead levels, and
      there was a strong inverse correlation with selenium concentrations. Lead and
      selenium concentrations tended to be similar in the cases and controls, both in
      the study population as a whole and after the removal from the analysis of the
      patients with the highest degree of disability. In the patients with limited
      disability, cadmium concentrations were higher than in the controls. Our findings
      lend limited support to a possible involvement of cadmium, but not lead, in the
      etiology of sporadic amyotrophic lateral sclerosis, and strongly suggest that
      short-term indicators of exposure are inadequate to investigate the relationship
      between selenium and the disease.

PMID- 9239529
TI  - Mental imagery of photic stimulation provokes paroxysmal EEG activity in a
      photosensitive patient who self-induces seizures.
AB  - This article reports a case of a 14 year-old male photosensitive epileptic
      patient who was able to induce fits subjectively by the mental imagery of the
      effective visual stimuli. The patient underwent a comprehensive
      electroencephalographic (EEG) examination including hyperventilation. The basic
      EEG showed abnormalities. Intermittent photic (IPS) and pattern stimulations
      (PtnS), evoked photo and pattern paroxysmal responses (PPRs) within a wide range
      of frequencies for 2-50 flashes per second (fps) and 0.5-6 cycles per degree
      (cdp) respectively. The patient was able to reconstruct the PPRs mentally on
      exposure to the effective stimuli of 25 and 50 fps, and 2.0 and 3.25 cpd
      respectively. His cognitive functions were not affected when exposed to
      photostimulation. However, on exposure to pattern stimulation, he became totally
      confused and his consciousness was impaired. These findings showed that self
      induction of fits in photosensitive epilepsy is a mental phenomenon which takes
      place with or without loss of cognitive function depending on the rate and
      frequency of the physical and 'imagined' stimuli.

PMID- 9239530
TI  - Radiation-induced sarcoma of the skull: report of two cases.
AB  - The authors describe two cases of sarcomas of the skull following cranial
      irradiation in patients treated for other neoplasms, acute lymphatic leukemia,
      and astrocytoma, respectively. The patients (one man and one woman: mean age 24.5
      years) developed sarcomas within the irradiated field after a mean latency period
      of 11.5 years. Histologically, the tumor proved to be a fibrosarcoma. Despite
      aggressive surgery and other therapy, the survival of the patients was short (10
      and 8 months, respectively). The pathological and clinical aspects of this
      unusual complication are analyzed with reference to 41 cases taken from the world
      literature.

PMID- 9239531
TI  - Vasculitic neuropathy associated with beta-haemolytic streptococcal infection: a
      case report.
AB  - Vasculitic neuropathy is rarely associated with a definable collagen vascular
      disease. Peripheral neuropathy may be the sole manifestation of vasculitis, and
      the aetiology is frequently unknown. We here report the case of a woman
      presenting mononeuritis multiplex, whose sural nerve biopsy was diagnostic of
      necrotizing vasculitis. There was serological evidence of preceding beta
      haemolytic streptococcal infection. We assume that vasculitic neuropathy can be
      included among the possible sequelae of streptococcal infections.

PMID- 9239532
TI  - Conjugal amyotrophic lateral sclerosis: toxic clustering or change?
AB  - We describe a southern Italian couple, married for 28 years, who developed
      amyotrophic lateral sclerosis (ALS) within 30 months of each other. They had
      drunk water taken from an artesian well for nearly thirty years. Samples of the
      water were investigated in the search for heavy metals and pesticides using high
      performances liquid chromatography, gas chromatography and absorption
      spectrometry. No heavy metals, pesticides or known environmental toxic substances
      were found in significant concentration. This would seem to support the view that
      conjugal ALS in Caucasians is due to mere coincidence.

PMID- 9239533
TI  - Morphological and functional study of a case of superficial siderosis of the
      central nervous system.
AB  - We here describe a case of superficial siderosis (SS) of the central nervous
      system (CNS), occurring in a patient with a previous lesion of the brachial
      plexus. Of the only 96 cases that have been described in the literature so far,
      there are now five with a positive history of a lesion due to the evulsion of the
      roots of the brachial plexus. This is the first time that, in addition to CT and
      MRI morphological investigations, an SS patient has also been studied
      metabolically by means of PET in an attempt to find new clues that may help to
      clarify the pathogenesis of the disease.

PMID- 9239534
TI  - A case-control study on alcohol and seizures: study design, protocol, and data
      collection. The ALCE (Alcohol and Epilepsy) Study Group.
AB  - We designed a multicenter case control study to evaluate whether chronic
      alcoholism and alcohol are risk factors for developing a first generalized tonic
      clonic epileptic seizure. Cases were 278 patients (92 women, 186 men), with a
      first generalized tonic-clonic seizure (either idiopathic or symptomatic),
      matched to 556 controls for center, sex, age, and weekday of the seizure.
      Information on risk factors was obtained through a questionnaire. This paper
      focuses on the study design (selection of cases and choice of controls), the
      validity of the instruments for data collection, and the strategies of study
      conduction (interviews, use of proxy respondents). Inter-rater agreement was
      excellent for drinking status, patterns of drinking, and broad indicators of
      consumption (yes/no). Agreement was variable for the number of servings/week, but
      was excellent (r = 0.91) for a summary of daily alcohol intake.

PMID- 9239535
TI  - Complete spontaneous thrombosis of a giant aneurysm of the intracavernous carotid
      artery.

PMID- 9239536
TI  - Mitochondrial disorders: an overview.

PMID- 9239537
TI  - Nuclear control of respiratory chain expression in mammalian cells.
AB  - The majority of gene products for mitochondrial respiratory function are encoded
      in the nuclear genome. These include most of the respiratory subunits and all of
      the proteins that regulate the mitochondrial genetic system. One approach to
      understanding nucleo-mitochondrial interactions in mammalian cells is to identify
      the nuclear transcription factors that are common to the expression of these gene
      products. This has led to the purification and molecular cloning of nuclear
      respiratory factors, NRF-1 and NRF-2. The DNA binding and transcriptional
      specificities of these proteins have implicated them in the expression of many
      respiratory subunits along with key components of the mitochondrial
      transcription, replication, and heme biosynthetic machinery. In addition, tissue
      specific transcription factors have been linked to the coordinate synthesis of
      contractile proteins and muscle-specific respiratory subunits whereas other more
      ubiquitous factors may have a dual function in nuclear and mitochondrial gene
      activation. These findings provide a framework for further investigations of the
      nuclear genetic mechanisms that integrate the expression of the respiratory
      apparatus with that of other cellular systems during growth and development.

PMID- 9239538
TI  - Disorders of nuclear-mitochondrial intergenomic signalling.
AB  - In addition to sporadic or maternally-inherited mutations of the mitochondrial
      genome, abnormalities of mtDNA can be transmitted as mendelian traits. The latter
      are believed to be caused by mutations in still unknown nuclear genes, which
      deleteriously interact with the mitochondrial genome. Two groups of mtDNA-related
      mendelian disorders are known: those associated with mtDNA large-scale
      rearrangements and those characterized by severe reduction of the mtDNA copy
      number. The most frequent presentation of the first group of disorders is an
      adult-onset encephalomyopathy, defined clinically by the syndrome of progressive
      external ophthalmoplegia "plus", genetically by autosomal dominant transmission
      of the trait, and molecularly by the presence of multiple deletions of mtDNA. The
      second group of disorders comprises early-onset, organ-specific syndromes,
      associated with mtDNA depletion, that are presumably transmitted as autosomal
      recessive traits. Linkage analysis and search for candidate genes are two
      complementary strategies to clarify the molecular basis of these disorders of the
      nuclear-mitochondrial intergenomic signalling.

PMID- 9239541
TI  - Leber hereditary optic neuropathy: how do mitochondrial DNA mutations cause
      degeneration of the optic nerve?
AB  - Leber hereditary optic neuropathy (LHON) is an inherited form of bilateral optic
      atrophy in which the primary etiological event is a mutation in the mitochondrial
      genome. The optic neuropathy involves a loss of central vision due to
      degeneration of the retinal ganglion cells and optic nerve axons that subserve
      central vision. The primary mitochondrial mutation is necessary--but not
      sufficient--for development of the optic neuropathy, and secondary genetic and/or
      epigenetic risk factors must also be present although they are poorly defined at
      the present time. There is broad agreement that mutations at nucleotides 3460,
      11778, and 14484 are primary LHON mutations, but there may also be other rare
      primary mutations. It appears that the three primary LHON mutations are
      associated with respiratory chain dysfunction, but the derangements may be
      relatively subtle. There is also debate on whether there are mitochondrial
      mutations that have a secondary etiological or pathogenic role in LHON. The
      specific pattern of the optic neuropathy may arise from a "chokepoint" in the
      optic nerve in the region of the nerve head and lamina cribosa, and which may be
      more severe in those LHON family members who become visually affected. It is
      hypothesized that the respiratory chain dysfunction leads to axoplasmic stasis
      and swelling, thereby blocking ganglion cell function and causing loss of vision.
      In some LHON patients, this loss of function is reversible in a substantial
      number of ganglion cells, but in others, a cell death pathway (probably
      apoptotic) is activated with subsequent extensive degeneration of the retinal
      ganglion cell layer and optic nerve.

PMID- 9239540
TI  - Human cytochrome c oxidase: structure, function, and deficiency.
AB  - As the terminal component of the mitochondrial respiratory chain, cytochrome c
      oxidase plays a vital role in cellular energy transformation. Human cytochrome c
      oxidase is composed of 13 subunits. The three major subunits form the catalytic
      core and are encoded by mitochondrial DNA (mtDNA). The remaining subunits are
      nuclear-encoded. The primary sequence is known for all human subunits and the
      crystal structure of bovine heart cytochrome c oxidase has recently been
      reported. However, despite this wealth of structural information, the role of the
      nuclear encoded subunits is still poorly understood. Yeast cytochrome c oxidase
      is a close model of its human counterpart and provides a means of studying the
      effects of mutations on the assembly, structure, stability and function of the
      enzyme complex. Defects in cytochrome c oxidase function are found in a
      clinically heterogeneous group of disorders. The molecular defects that underlie
      these diseases may arise from mutations of either mitochondrial or the nuclear
      genomes or both. A significant number of cytochrome c oxidase deficiencies, often
      associated with other respiratory chain enzyme defects, are attributed to
      mutations of mtDNA. Mutations of mtDNA appear, nonetheless, uncommon in early
      childhood. Pedigree analysis and cell fusion experiments have demonstrated a
      nuclear involvement in some infantile cases but a specific genomic lesion has not
      yet been reported. Detailed analyses of the many steps involved in the biogenesis
      of cytochrome c oxidase, often pioneered in yeast, offer several starting points
      for further molecular characterizations of cytochrome c oxidase deficiencies
      observed in clinical practice.

PMID- 9239539
TI  - Mitochondrial DNA mutations and pathogenesis.
AB  - Approximately there years ago, this journal published a review on the clinical
      and molecular analysis of mitochondrial encephalomyopathies, with emphasis on
      defects in mitochondrial DNA (mtDNA). At the time, approximately 30 point
      mutations associated with a variety of maternally-inherited (or rarely, sporadic)
      disorders had been described. Since that time, almost twenty new pathogenic mtDNA
      point mutations have been described, and the pace of discovery of such mutations
      shows no signs of abating. This accumulating body of data has begun to reveal
      some patterns that may be relevant to pathogenesis.

PMID- 9239542
TI  - Mitochondrial dysfunction in neurodegeneration.
AB  - Numerous toxins are known to interfere with mitochondrial respiratory chain
      functions. Use has been made of these in the development of pesticides and
      herbicides, and accidental use in man has led to the development of animal models
      for human disease. The propensity for mitochondrial toxins to induce neuronal
      cell death may well reflect not only their metabolic pathways but also the
      sensitivity of neurons to inhibition of oxidative phosphorylation. Thus, the
      accidental exposure of humans to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and
      to 3-nitropropionic acid had led to primate models of Parkinson's disease and
      Huntington's Disease, respectively. These models were made all the more
      remarkable when identical biochemical deficiencies were identified in relevant
      areas of human suffering from the respective idiopathic diseases. The place of
      complex I deficiency in Parkinson's disease remains undetermined, but there is
      recent evidence to suggest that, in some cases at least, it may play a primary
      role. The complex II/III deficiency in Huntington's disease is likely to be
      secondary and induced by other pathogenetic factors. The potential to intervene
      in the cascade of reactions involving mitochondrial dysfunction and cell death
      offers prospects for the development of new treatment strategies either for
      neuroprotection in prophylaxis or rescue.

PMID- 9239545
TI  - Anatomical factors predisposing to focal dystonia in the musician's hand-
      principles, theoretical examples, clinical significance.
AB  - In this paper, anatomical interconnections between tendons, between tendons and
      their environment, and anatomical constraints on joint mobility are considered as
      possible causes of focal dystonia in the hand of the musician. By hypothesis,
      focal dystonias arise when the constraints on movement resulting from these
      anatomic limitations impede playing movements with sufficiently low energy
      expenditure. This hypothesis is modelled for connections between the deep finger
      flexors. The displacements, forces, stresses, and work per volume in the finger
      motors in some common piano playing movements are calculated. The results
      indicate that with mentioned connections, in certain movements the extensor and
      lumbrical, and in others the lumbrical and interossei are most strained, while
      the interossei may become the main power source in loaded instrumental movements.
      Also discussed are compensatory movements. The biomechanical principles of
      surgical and conservative treatment are summarised.

PMID- 9239543
TI  - Mitochondrial implication in accidental and programmed cell death: apoptosis and
      necrosis.
AB  - Both physiological cell death (apoptosis) and at least some cases of accidental
      cell death (necrosis) involve a two-step-process. At first level, numerous
      physiological or pathological stimuli can trigger mitochondrial permeability
      transition which constitutes a rate-limiting event and initiates the common phase
      of the death process. Mitochondrial permeability transition (PT) involves the
      formation of proteaceous, regulated pores, probably by apposition of inner and
      outer mitochondrial membrane proteins which cooperate to form the mitochondrial
      PT pore complex. Inhibition of PT by pharmacological intervention on
      mitochondrial structures or mitochondrial expression of the apoptosis-inhibitory
      oncoprotein Bcl-2 thus can prevent cell death. At a second level, the
      consequences of mitochondrial dysfunction (collapse of the mitochondrial
      transmembrane potential, uncoupling of the respiratory chain, hyperproduction of
      superoxide anions, disruption of mitochondrial biogenesis, outflow of matrix
      calcium and glutathione, and release of soluble intermembrane proteins) can
      entail a biogenetic catastrophe culminating in the disruption of plasma membrane
      integrity (necrosis) and/or the activation and action of apoptogenic proteases
      with secondary endonuclease activation and consequent oligonucleosomal DNA
      fragmentation (apoptosis). The acquisition of the biochemical and ultrastructural
      features of apoptosis critically relies on the liberation of apoptogenic
      proteases or protease activators from the mitochondrial intermembrane space. This
      scenario applies to very different models of cell death. The notion that
      mitochondrial events control cell death has major implications for the
      development of death-inhibitory drugs.

PMID- 9239546
TI  - Testing the daily stress stimulus theory of bone adaptation with natural and
      experimentally controlled strain histories.
AB  - Theories of bone adaptation generally consider that a departure in some feature
      of the normal homeostatic mechanical stimulus governs mechanical adaptation.
      Specifically, the 'daily stress stimulus' theory commonly used in computational
      models of bone adaptation suggests that the mechanical stimulus arises from a
      synthesis of the peak magnitudes from each loading event during a day. In this
      study, the homeostatic daily strain history of the adult turkey ulna was
      established by categorizing and counting the natural wing activities of adult
      male turkeys over a full 24h period. Strain signals were recorded in vivo for
      each activity type at three mid-diaphysis sites using stacked rosette strain
      gages. Following surgical isolation and transverse metaphyseal pinning of the
      ulnae, additional strain signals were recorded during controlled axial and
      torsional loading regimens associated with documented maintenance, loss, or
      addition of bone mass. When the present data were incorporated into the daily
      stress stimulus formulation, the theory did not consistently discriminate
      maintenance versus formation regimens, i.e., some maintenance regimens were
      associated with a substantially higher daily stimulus than some regimens causing
      bone formation.

PMID- 9239544
TI  - Treatment of mitochondrial disease.
AB  - Defects of the mitochondrial genome are widely recognized as important causes of
      disease in man. Patients may present at any age with clinical symptoms that vary
      from acute episodes of lactic acidosis in infancy to severe neurodegenerative
      illness in adulthood. While modern molecular genetic techniques have facilitated
      major advances in the diagnosis and characterization of specific molecular
      defects, treatment for the majority of patients remains supportive in the absence
      of definitive biochemical therapies. As a consequence, the possibilities for
      mitochondrial DNA gene therapy must be considered. In this review, we will
      evaluate the current biochemical strategies available to clinicians for the
      management of patients with mitochondrial disease and examine the possible
      approaches to the gene therapy of mitochondrial DNA defects.

PMID- 9239547
TI  - Geometric and inertial data of the trunk in adult males.
AB  - In this study investigations on geometric and inertial quantities of 15 male
      patients' trunks are described. Layers of 8 mm were scanned using computerized
      tomography. Thorax, abdomen, pelvis, and two shoulders and their unchangeable and
      changeable (muscle, fat, and skin) tissues were investigated. The trunk was also
      divided into portions and subportions according to anthropological landmarks. By
      comparing subportions to right non-circular frusta, the volume of the trunk is
      obtained. Volume, mass, and density of trunk's segments and their tissues are
      given. The location of the centers of mass of the segments is also provided.
      Regression equations are presented for the calculation of volume of tissues and
      of subportions. Application of the data for locating the center of mass of the
      body, for building anthropometric dummies, and for calculating the load acting on
      any level of a spine are presented.

PMID- 9239548
TI  - Pinching in longitudinal and alternate osteons during cyclic loading.
AB  - Pinching is a degrading phenomenon which occurs during cyclic loading of certain
      materials. A change in the slope of the deflection curve reveals pinching
      lesions, either flexural cracks or bond degradation, cause pinching. This paper
      investigates pinching for 20 longitudinal and 18 alternate fully calcified
      osteonic samples of cylindrical shape and 500 micron length. Each sample was
      axially loaded beyond the proportional limit using an electromechanical device
      acting as a transducer of the variations in length of the sample into changes in
      the resonance frequency of a microwave micrometer. A cubic polynomial served as a
      mathematical model to investigate the stress-strain diagrams at the first and
      last cycles through the study of strain limits, stiffness and pinching
      behaviours, and energy absorption. The hysteretic behaviour of the two types of
      osteons differs and is far from ideal. The presence of pinching may derive from
      the existence of longitudinal fibrils, in particular the yielding of the
      incompletely calcified ones. In longitudinal osteons consisting mainly of
      longitudinal collagen fibrils, the deformation under compression is not protected
      by lamellae consisting of transverse fibrils, therefore the lesions inducing
      pinching are magnified. In contrast, in alternate osteons, where the fibrils
      having a longitudinal orientation are reduced and protected by lamellae
      containing transversely oriented fibrils, the lesions-inducing pinching are
      lessened.

PMID- 9239549
TI  - Spine loading during trunk lateral bending motions.
AB  - Increases in lateral trunk velocities have been identified as a mechanism for
      increasing the risk of low-back disorder. Previous studies have identified an
      increase in coactivation of the trunk musculature during lateral bends, but no
      studies have evaluated how spine loading changes as lateral trunk velocity
      increases. Twelve subjects were asked to lift loads laterally at one static and
      three dynamic velocities. Ten trunk muscle activities and trunk kinematics were
      documented and used as input parameters to an EMG-assisted model to evaluate
      spine loading. Muscle coactivation was observed in all lateral bends.
      Coactivation significantly increased during dynamic trials compared to the static
      trials. Coactivity increased spinal loads by as much as 25% compared to values
      predicted by models that did not consider coactivity. Movements to the right
      significantly increased spine loadings (252 N increase in compression) compared
      to movements to the left. Spine compression, A-P shear, and lateral shear all
      increased in the dynamic trials compared to the static conditions. Peak
      compression increased by an average of 525 N at 45 degrees s-1 compared to static
      loading. Compression and lateral shear increased monotonically as trunk velocity
      increased. It is expected that this combined (compression and lateral shear)
      loading is the mechanism for increased risk observed in industry.

PMID- 9239551
TI  - Mechanical implications of humero-ulnar incongruity--finite element analysis and
      experiment.
AB  - Previous studies show that the humero-ulnar joint is physiologically incongruous
      [Eckstein et al. (1995a) Anat. Rec. 243, 318-326] and exhibits a bicentric
      (ventro-dorsal) distribution of subchondral mineralization [Eckstein et al.
      (1995b) J. Orthop. Res. 13, 286-278]. We therefore asked: (1) Does humero-ulnar
      incongruity bring about a bicentric distribution of contact pressure? (2) Do
      tensile stresses occur in the subchondral bone of the trochlear notch that are in
      the same order of magnitude as the compressive stresses? (3) Do ventral and
      dorsal maxima of subchondral bone density correlate with a bicentric distribution
      of strain energy density? To that end, a two-dimensional finite element model was
      designed. The shape and material properties of the bones were based on CT and the
      boundary conditions selected to agree with resisted elbow extension at 90 degrees
      of flexion. The incongruity and contact areas were determined experimentally from
      casts, and the pressure distribution with Fuji Prescale film. In the model and
      the experiment contact stresses above 2 MPa were recorded in the ventral and
      dorsal parts of the joint, and values below 0.5 MPa in the depth of the notch. In
      the model, tensile stresses of 2.9 MPa were observed in the subchondral bone of
      the ulna, but not in the humerus. The subchondral strain energy density yielded a
      bicentric pattern in a model with homogeneous subchondral bone properties. It is
      shown that humero-ulnar incongruity brings about a bicentric distribution of
      contact pressure, a tensile stress in the notch that is in the same order of
      magnitude as the compressive stress, and a distribution of strain energy density
      that correlates with subchondral density patterns.

PMID- 9239550
TI  - How muscle architecture and moment arms affect wrist flexion-extension moments.
AB  - The purpose of this investigation was to determine how the moment arms and
      architecture of the wrist muscles influence their isometric moment-generating
      characteristics. A three-dimensional computer graphic model was developed that
      estimates the moment arms, maximum isometric forces, and maximum isometric
      flexion-extension moments generated by 15 muscles about the wrist over a range of
      wrist flexion angles. In combination with measurements of muscle strength, we
      used this model to answer three questions: (1) why is peak wrist flexion moment
      greater than peak extension moment, (2) why does flexion moment vary more with
      wrist flexion angle than does extension moment, and (3) why does flexion moment
      peak with the wrist in a flexed position? Analysis of the model revealed that the
      peak flexion moment is greater than the peak extension moment primarily because
      of the larger (110%) summed physiologic cross-sectional area of the flexors. The
      larger variation of flexion moment with flexion angle is caused mainly by greater
      variation of the moment arms of the major wrist flexors with flexion angle. The
      location of the peak flexion moment is determined by the wrist flexion moment
      arms (which tend to increase with wrist flexion) in combination with the force
      length characteristics of these muscles.

PMID- 9239552
TI  - Changes in the lower leg moment of inertia due to child's growth.
AB  - During growth the size and shape of the child's body changes. It is not clear
      whether the shape of a body segment changes proportionally in children between
      the age 5 and 18 years. The aim of this study is to describe these changes for
      the lower leg moment of inertia in a population of children. The segment moment
      of inertia describes the mass distribution along the body segment axis. The
      moment of inertia of the lower leg (including the foot) was measured by the free
      oscillation technique in 90 healthy children (61 boys and 29 girls) between and 5
      and 18 years of age. The period of free oscillation was measured with and without
      external mass loading. The moment of inertia was calculated using a relation
      between the mass and the period of oscillation. A two-cylinder model of constant
      body density was used to predict the moment of inertia. Anthropometric
      measurements of length of the lower leg and foot, the circumference of the knee,
      ankle and foot were made. Experimental and model data of the lower leg of inertia
      were described by a fifth power function of body height. The experimental and
      model data showed high degree of convergence, confirming that the segment growth
      of the human body can be treated like the volume growth of a cylindrical object
      of constant body density. Thus it was experimentally confirmed that the lower leg
      segment growth between age 5 and 18 years may be considered as proportional.

PMID- 9239553
TI  - Effect of skin movement on the analysis of skeletal knee joint motion during
      running.
AB  - It is not known how well skin markers represent the skeletal knee joint motion
      during running. Hence the purpose of this investigation was to compare the skin
      marker derived tibiofemoral motion with the skeletal tibiofemoral motion during
      running. In addition to skin markers attached to the shank and thigh, triads of
      reflective markers were attached to bone pins inserted into the tibia and femur.
      Three-dimensional kinematics of the stance phase of five running trials were
      recorded for three subjects using high-speed cine cameras (200 Hz). The knee
      motion was expressed in terms of Cardan angles calculated from both the external
      and skeletal markers. Good agreement was present between the skin and bone marker
      based knee flexion/extension. For abduction/adduction and internal/external knee
      rotation, the difference between skeletal and external motion was large compared
      to the amplitude of these motions. Average errors relative to the range of motion
      during running stance were 21% for flexion/extension, 63% for internal/external
      rotation, and 70% for abduction/adduction. The errors were highly subject
      dependent preventing the realization of a successful correction algorithm. It was
      concluded that knee rotations other than flexion/extension may be affected with
      substantial errors when using skin markers.

PMID- 9239555
TI  - Development and validation of a series of three-dimensional finite element models
      of the equine metacarpus.
AB  - Three-dimensional finite element (FE) models of the left metacarpi of five adult
      horses were developed from quantitative computed tomography data, using the
      algorithms of Keyak et al. (1990, J Biomed. Engng 12, 389-397). The metacarpi
      were then equipped with 12 rosette strain gauges and loaded non-destructively in
      a mechanical testing machine. The bones and the models were loaded in axial
      compression, with the load evenly distributed across the distal row of carpal
      bones, and with a point load placed mediad to the sagittal midline, to a load
      equivalent to three times body weight (-15 kN); and in sagittal four-point
      bending to -2 kN. Maximum and minimum principal strains from the models were
      compared with those at the strain gauge rosettes. There were significant (p <
      0.001) and strong (0.69 < r < 0.90) correlations between predicted and observed
      surface principal strains, most often resolving as second- or third-order
      polynomial relationships. In most cases, particularly at extreme strain
      magnitudes, the models tended to overestimate the observed strain magnitudes.
      These data suggest that the models are robust and accurate predictors of surface
      strains. Validation of these models lends further support for the use of this
      method of automated three-dimensional FE modeling, with its emphasis on accurate,
      individualized portrayal of structural geometry and material distribution, in
      research applications, and specifically for the use of these models in the study
      of the biology and mechanics of the equine metacarpus.

PMID- 9239554
TI  - Conjugate imagery in the automated reproduction of three dimensional coordinates
      from two dimensional coordinate data.
AB  - The three-dimensional video analysis of human motion commonly utilises automated
      image processing and digitisation processes to produce real-time unidentified two
      dimensional coordinate data of segmental markers. In what can be a time-consuming
      process the two-dimensional data are then identified and tracked to produce three
      dimensional coordinates. This paper presents an approach to the automated
      reproduction of three-dimensional coordinates from two-dimensional coordinates
      data. Conjugate imaging techniques were utilised in the development of four
      criterion measures for determining the validity of conjugate (corresponding)
      image points. An algorithm based on the criterion measures was then developed for
      the automated reproduction of three dimensional coordinates from camera image
      coordinate data. The algorithm was tested with a 55 point marker system viewed in
      four video cameras (digitisation error approx. 0.2%, lab point separation > or =
      6 cm). The success of the algorithm was dependent on the closeness of markers,
      the accuracy of the photogrammetric system, and the number of markers visible in
      two camera images. The present research has developed techniques based on
      conjugate imagery for the automated reproduction of three-dimensional coordinates
      from two-dimensional data, and provided a bases for further development of
      automated three-dimensional tracking.

PMID- 9239556
TI  - Measurements of permeability in human calcaneal trabecular bone.
AB  - 2.36 cm diameter cores of trabecular bone (n = 22), oriented in the mediolateral
      direction, were obtained from fresh-frozen calcanei of 16 cadavers ranging in age
      from 32 to 89 yr. The cores were defatted and tested to determine values for
      permeability along the cylinder axis. Permeability values (0.4-11 x 10(-9)m2)
      were found to be strongly correlated with specimen porosity (78-92%) through a
      linear relationship (r2 = 0.91). These results provide essential information for
      the biphasic or poroelastic modeling of fluid-filled trabecular bone at this
      location.

PMID- 9239557
TI  - A mathematical approximation for the solution of a static indentation test.
AB  - The classical contact problem of the indentation of a thin compressible linear
      elastic layer bonded to a rigid substrate is considered. Closed-form mathematical
      approximations of the deformation are presented for the cases of plane
      indentation by a rectangular block and three dimensional indentation by a plane
      ended (axisymmetric) cylinder. The approximations are analyzed in the context of
      a static indentation test by comparison of applied load values to those obtained
      using a classical integral transform solution. In the case of plane indentation,
      the mathematical and classical predictions agree to within 2% relative error for
      aspect ratios between 0.1 and 1.0 and apparent Poisson ratio between 0.0 and 0.3.
      Comparisons for the axisymmetric case indicate a similar pattern. The main
      advantage of the new approach is that it yields closed-form approximations of the
      static indentation solution which can also capture the essential singular
      behavior.

PMID- 9239558
TI  - A method to quantify the fiber kinematics of planar tissues under biaxial
      stretch.
AB  - We have developed a method for measuring fiber kinematics in two-dimensional soft
      collagenous tissues. The technique combines small-angle light scattering (SALS)
      and biaxial stretch controlled by simultaneous optical strain measurement.
      Preliminary findings on porcine aortic valve leaflets and bovine pericardium
      indicate that fiber kinematics are highly tissue specific and are generally non
      affine. The mobility of the fibers within each tissue seems to be specialized to
      perform a distinct physiological function. Quantitative knowledge of a tissue's
      angular fiber distribution and its transformation during biaxial stretch is
      critical for microstructural modeling of planar tissues. Our results underscore
      the importance of measuring fiber kinematics for each specific tissue type that
      is to be modeled.

PMID- 9239559
TI  - A high-frequency shear device for testing soft biological tissues.
AB  - Accurate mechanical property data obtained at large shear deformations and high
      frequencies are a fundamental component of realistic numerical simulations of
      soft tissue injury. Although many commercial systems exist for testing shear
      properties of viscoelastic materials with properties similar to soft biological
      tissue, none are capable of determining properties at high loading rates
      necessary for modeling soft tissue injury. Previous custom shear testing systems,
      though capable of high-frequency loading, indirectly measure tissue properties by
      using analytical corrections for inertial effects. To address these limitations,
      a new custom designed oscillatory shear testing apparatus (STA) capable of
      testing soft biological tissues in simple shear has been constructed and
      validated. Through a proper selection of sample thickness, direct measurement of
      material properties at high frequencies is achieved mechanically without
      analytical inertial adjustments. The complex shear modulus of three mixtures of
      silicone gel with viscoelastic properties in a range similar to soft biological
      tissue was characterized in the STA over a dynamic frequency range of 20-200 Hz
      and validated with a commercially available solids rheometer. The frequency
      dependent complex shear modulus measurements of the STA were within 10% of the
      rheometer measurements for all mixtures over the entire frequency range tested.
      The STA represents substantive improvement over current shear testing methods by
      providing direct measurement of the shear behavior of soft viscoelastic material
      at high frequencies. Mechanical property data gained from this device will
      provide a more realistic basis for numerical simulations of biological
      structures.

PMID- 9239560
TI  - Crack growth resistance in cortical bone: concept of microcrack toughening.
AB  - The role of microcracking in cortical bone as a toughening mechanism has been
      investigated in conjunction with the variation in fracture toughness with crack
      length. Fracture toughness tests were conducted on miniaturised compact tension
      specimens made from human and bovine cortical bone and the resultant
      microstructural damage, present in the form of microcracking on the surface, was
      analysed around the main propagating crack. It was found that the fracture
      toughness (Kc) and the cumulative number of microcracks increased linearly with
      crack extension in human and bovine cortical bone, although both Kc and number of
      microcracks were considerably higher in the latter case. Based on these results,
      a mechanism, derived from the resistance (R) curve concept developed for
      microcracking brittle solids, is proposed to explain the fracture of cortical
      bone, with microcracking distributed between a frontal process zone and a
      significant process zone wake. Evidence to support this mechanism is given from
      the existing bone literature, detailed scanning electron microscopical
      observations and the distribution of microcracks in the process zone wake.

PMID- 9239561
TI  - The normal stress effect and equilibrium friction coefficient of articular
      cartilage under steady frictional shear.
AB  - During creep or stress relaxation, articular cartilage exhibits a time-dependent
      friction coefficient which has been shown to reach an equilibrium value, mu eq,
      as the tissue deformation equilibrates. This study investigates the frictional
      properties of articular cartilage explants under steady frictional shear and
      constant compressive strain after the tissue reaches stress-relaxation
      equilibrium. The two parameters measured are the normal force and frictional
      torque, from which the friction coefficient was then calculated. It is shown in
      this experimental study that: (1) Under a prescribed infinitesimal compressive
      strain, cartilage supports higher compressive normal stress under steady shear
      than it does in the absence of frictional shear. Furthermore, the normal stress
      increases with increasing sliding velocity, resulting in a velocity-dependent
      value of mu eq. The observed normal stress effectively increases the compressive
      stiffness of cartilage by a factor up to 3.1. (2) Under a prescribed steady
      frictional shear both the normal stress and frictional shear stress increase,
      though not proportionally, with increasing compressive strain, producing a
      decreasing friction coefficient. (3) This velocity-dependent normal stress effect
      is also shown to result, at least partly, from intrinsic properties of cartilage.
      The normal stress effect has not been previously reported for articular
      cartilage, and represents an intriguing mechanical response not commonly
      encountered in solids, though common in non-Newtonian fluids.

PMID- 9239562
TI  - Residual strain effects on the stress field in a thick wall finite element model
      of the human carotid bifurcation.
AB  - A three-dimensional finite element model of the carotid artery bifurcation was
      constructed in order to determine the stress field and assess the modification of
      the stress field when residual strain is taken into account. Residual strain in
      the carotid bifurcation was characterized by experimental observations. According
      to these observations, a geometrical model of the carotid artery was constructed
      to exhibit a state free of strain. Appropriate boundary conditions were applied
      to yield the correct geometry in the unloaded state, and physiological levels of
      pressure and axial stretching were applied. The model took into account the
      varying thickness of the arterial wall along the bifurcation. For modeling
      purposes, the material was considered to be hyperelastic, incompressible,
      homogenous and isotropic. For comparison, a similar model of the carotid artery
      which does not include the effects of residual strain was also created. The
      results demonstrate that in the model of the carotid artery bifurcation with
      residual strain, the distribution of maximum principal stress along the inner
      wall and the circumferential stress throughout the wall is much more uniform than
      in the model without residual strain. The ratio between the stress at the inner
      and the outer walls is highest at the lateral wall of the carotid sinus; this is
      the same location known to be a site of low and oscillatory fluid wall shear
      stress, and the principal location of early intimal thickening. These results
      suggest that the localization of atherosclerosis in the carotid artery may be due
      to local variations in both fluid wall shear stress and solid wall stress.

PMID- 9239563
TI  - Normal kinematics of carpal bones: a three-dimensional analysis of carpal bone
      motion relative to the radius.
AB  - Normal carpal kinematics were studied in 22 cadaver specimens using a biplanar
      radiography method. The kinematics of the trapezium, capitate, hamate, scaphoid,
      lunate, and triquetrum were determined during wrist motion in sagittal and
      coronal planes. The results were expressed using the concept of the screw
      displacement axis and converted to describe the magnitude of rotation about and
      translation along three axes (X-axis: pronation-supination axis, Y-axis: flexion
      extension axis, and Z-axis: radial-ulnar deviation axis) commonly used for the
      wrist. The orientation of these axes is expressed relative to the radius. Within
      the proximal carpal row, considerable differences of carpal behavior around the Y
      axis were observed during sagittal plane motion of the wrist. The scaphoid
      exhibited the greatest magnitude of rotation, and the lunate the least. The
      magnitude of rotation of the carpal bones around the X-axis during sagittal plane
      motion of the wrist was small. The proximal carpal bones exhibited some ulnar
      deviation in 60 degrees of wrist flexion. During coronal plane motion of the
      wrist, the magnitude of radial-ulnar deviation of the distal carpal bones was
      mutually similar and generally of a greater magnitude than that of the proximal
      carpal bones. The proximal carpal bones experienced some flexion during radial
      deviation of the wrist and extension during ulnar deviation of the wrist.
      Translation was generally minimal in all carpal bones throughout wrist motion.
      This study reports results from the largest cadaver wrist kinematics study
      completed to date. The accuracy of the current method was improved when compared
      to previous studies. A sufficient number of specimens to allow statistical
      comparison was used and minimal interspecimen variability was noted. This study
      enabled a precise description of quantitative analyses of normal carpal
      kinematics relative to the radius.

PMID- 9239564
TI  - The effects of cement-stem debonding in THA on the long-term failure probability
      of cement.
AB  - The damage accumulation failure scenario is one of the most prominent ones of
      cemented THA reconstruction, and involves the accumulation of mechanical damage
      in materials and interfaces due to repetitive dynamic loading eventually
      resulting in gross loosening. This study addresses this scenario by combining
      finite element techniques with the theory of continuum damage mechanics, to
      analyze the damage accumulation process in the cement mantle. It was investigated
      how damage accumulation was affected by stem-cement debonding, and what the
      effects of a layer with poor bone quality around the cement mantle were. For the
      unbonded stem, it was determined if clinical migration rates can be explained by
      failure of the cement mantle, and whether cement failure promotes the formation
      of a pathway for debris at the stem-cement interface. It was found that stem
      cement debonding not only elevated the initial stress levels with a factor of
      about two to three as demonstrated in earlier studies, but remained to have an
      impact on the failure process of the cement mantle. Stem-cement debonding
      accelerated the failure process by a factor of four, and promoted the formation
      of a pathway for debris at the stem-cement interface, particularly when the bone
      support to the cement mantle was reduced. The amount of subsidence was only
      substantial when the damaged cement mantle was surrounded by a layer of bone with
      reduced stiffness. This study supports the hypothesis that the survival of
      cemented THA is enhanced by a firm and lasting bond between the stem and the
      cement mantle, although this may be difficult to realize clinically.

PMID- 9239565
TI  - The relative activation of elbow-flexor muscles in isometric flexion and in
      flexion/extension movements.
AB  - Coordination studies of multi-joint movements suggest that the central nervous
      system uses some constraints to reduce the large number of degrees of freedom of
      the arm. To gain insight into how the net joint torque is distributed among the
      muscles, intramuscular EMG recordings were made to determine the relative
      activation of five major elbow-flexor muscles during isometric, shortening, and
      lengthening contractions at three elbow joint angles. A regularization procedure
      was used to evaluate the effect of two different approaches used to calculate the
      relative contribution of elbow-flexor muscles to joint torque from intramuscular
      EMG recordings. The results demonstrate a significant increase of the relative
      contribution of the biarticular muscles for more extended elbow joint angles and
      for isotonic tasks relative to isometric tasks.

PMID- 9239566
TI  - Thermal and diffusion processes in laser-induced stress relaxation and reshaping
      of cartilage.
AB  - The thermodynamic characteristics of the 'bound-to-free' phase transformation of
      water are studied by means of differential microcalorimetry and FTIR
      spectroscopy. This phase transition controls the stress relaxation and reshaping
      of cartilage which we have observed previously under moderate laser heating. It
      is shown that the FTIR spectrum of bound water in cartilage differs from that of
      free water in cartilage, and that both show differences to the FTIR spectrum of
      pure water. The proportion of bound water in cartilage is found to be of the
      order 4%. We have examined water liberation and absorption kinetics and found
      them to be controlled by diffusion through the tissue and also by the bound-to
      free water transformation. The theoretical modelling and experimental data
      allowed calculation of diffusion coefficients and the activation energy for water
      transfer. The latter was found to be close to the heat of phase transformation of
      water. We have established that the drying and wetting processes in cartilage are
      reversible (fully or in a part, depending on the temperature of preliminary
      drying) and can be described by identical solutions of the diffusion problem,
      with coefficients of water diffusion being the same. The mechanism of water
      diffusion in cartilaginous tissue is also discussed.

PMID- 9239567
TI  - Theoretical study of the effect of stress-dependent remodeling on arterial
      geometry under hypertensive conditions.
AB  - Remodeling of arterial geometry was studied on the basis of a theoretical model.
      Sustained hypertension was simulated by a step increase in blood pressure. The
      artery was considered to be a thick-walled two-layer tube made of nonlinear
      elastic incompressible material. The basic hypothesis is that the artery remodels
      its zero-stress configuration in such a way that the strain and stress
      distributions in the arterial wall under hypertensive conditions are the same as
      under normotensive conditions. Using this hypothesis, a method for determining
      the geometrical dimensions of the zero-stress configuration of the hypertensive
      artery was proposed. To ensure uniqueness of the solution, two side conditions on
      the remodeling process are imposed: (a) the inner radius of the artery in the
      unloaded state remains unchanged; and (b) the ratio between the thickness of the
      inner and outer layer of the hypertensive artery in the zero-stress configuration
      is known. The model predicts that the arterial wall remodeling causes: (i) an
      increase of the wall thickness both in the unloaded and physiological states;
      (ii) an increase of the inner diameter of the hypertensive vessel under high
      pressure compared to the diameter of the normotensive artery under normal
      pressure; (iii) the opened-up configuration which arises when the unloaded
      arterial segment is cut radially still contains residual strains and stresses.
      These results are consistent with published experimental findings. It is
      speculated that the origin of residual stresses that exist in the unloaded and
      opened-up configurations is the stress-modulated growth.

PMID- 9239568
TI  - In vitro fatigue of human tendons.
AB  - The purpose of this study was to determine the fatigue behaviour of human tendons
      in vitro. The testing was accomplished with the use of specially designed grips
      and the local measurement of tendon cross-sectional area. Ninety specimens
      prepared from Extensor digitorum longus (EDL) tendons of the foot were subjected
      to a cyclic square tension-tension stress waveform at physiological frequencies.
      The maximum tensile stress was normalised to values corresponding to prescribed
      levels between 10% and 90% of the calculated ultimate tensile strength (UTS) of
      100 MPa. The minimum stress was set at 1% of the UTS. A replication of 10
      specimens per stress level allowed the use of statistical models for the
      distribution of fatigue life. Results followed a linear model, of form S = 101.3 
      14.8 log(N), relating the normalised stress to the median number of cycles to
      failure, therefore suggesting the absence of an endurance limit. The Weibull
      distribution was found to describe adequately the probability of failure at each
      stress level. A model which takes into account in vivo healing was proposed. This
      model was able to explain the presence of intact tendons throughout the lifetime
      of an individual.

PMID- 9239569
TI  - Leg cycling tracking by dynamic vision.
AB  - This study describes a method of tracking of human body limbs from a monocular
      sequence of perspective images. These objects and the associated articulations
      must be modelled. The principle of the method is based on the interpretation of
      image features as the three-dimensional perspective projections points of the
      object model and an iterative process method to compute the model position in
      accordance with the analysed image. This attitude is filtered (Kalman filter) to
      predict the model position relative to the next image of the sequence. The image
      features are extracted locally according to the computed prediction. Tracking
      experiments, illustrated in this study by a leg cycling sequence, have been
      conducted to demonstrate the viability of the approach.

PMID- 9239570
TI  - A computer-controlled mechanical culture system for biological testing of
      articular cartilage explants.
AB  - A computer-controlled mechanical culture system was designed to investigate the
      interaction between mechanical stimuli and the metabolism of articular cartilage.
      The main features of this system include the following capabilities: (1)
      Accurately controlled static, permanent cyclic or intermittent cyclic mechanical
      loads can be applied; (2) a great variety of different functions to load
      cartilage explants can be chosen; (3) a wide range of selectable forces (1.0-500
      N) and frequencies (up to 5.0 Hz) can be used to load explants; (4) cartilage
      explants can be cultured and loaded within a standard CO2-incubator for extended
      time periods; (5) similar culture conditions are provided within the loading
      chambers as in standard tissue culture plates; (6) simultaneously the applied
      load and the resulting displacement of specimens is measured, and (7) the load
      chambers are biocompatible, sterilizable, and non-corrosive. We expect that the
      newly designed mechanical culture system will increase our understanding on the
      regulatory role of direct mechanical pressure on the metabolic activities of
      chondrocytes.

PMID- 9239571
TI  - A comparison of automatic filtering techniques applied to biomechanical walking
      data.
AB  - The purpose of this study was to compare and evaluate six automatic filtering
      techniques commonly used in biomechanics for filtering gait analysis kinematic
      signals namely: (1) power spectrum (signal-to-noise ratio) assessment; (2)
      generalised cross validation spline; (3) least-squares cubic splines; (4)
      regularisation of Fourier series; (5) regression model and (6) residual analysis.
      A battery of 1440 signals representing the displacements of seven markers
      attached upon the surface of the right lower limbs and one marker attached upon
      the surface of the sacrum during walking were used; their original signal and
      added noise characteristics were known a priori. The signals were filtered with
      every technique and the root mean square error between the filtered and reference
      signal was calculated for each derivative domain. Results indicated that among
      the investigated techniques there is not one that performs best in all the cases
      studied. Generally, the techniques of power spectrum estimation, least-squares
      cubic splines and generalised cross validation produced the most acceptable
      results.

PMID- 9239572
TI  - Optimal digital filtering requires a different cut-off frequency strategy for the
      determination of the higher derivatives.
AB  - The present study investigated four different filtering and differentiation
      sequences for the calculation of the higher derivatives from noisy displacement
      data when using a second-order Butterworth filter and first-order finite
      differences. These were: (1) the conventional sequence (i.e. filtering the
      displacement data and then differentiating); (2) filtering the displacement with
      a different cut-off frequency depending upon optimal 0th, 1st and 2nd
      derivatives; (3) double filtering and differentiation (only for acceleration);
      and (4) differentiation and then filtering separately in each derivative domain,
      i.e. treating the noisy higher derivatives as individual signals. Thirty levels
      of time domain and 30 levels of frequency domain computer-generated pure noise
      signals, were superimposed on 24 reference signals which simulated the medial
      lateral, anterior-posterior and vertical displacement patterns of eight markers
      attached to the lower extremity segments during walking. The optimum cut-off
      frequency for the displacement velocity and acceleration data was calculated as
      the one that produced the minimum root mean square error between the reference
      and noisy data in each derivative domain. The results indicated that the
      conventional strategy has to be reconsidered and modified, as the best results
      were obtained by the second strategy. The optimum cut-off frequency for
      acceleration was lower than that required for the velocity which in turn was
      lower than the optimum cut-off frequency for displacement. The findings of the
      present study will contribute to the development of existing and future automatic
      filtering techniques based on digital filtering.

PMID- 9239573
TI  - Accuracy of an electromagnetic tracking device.

PMID- 9239574
TI  - Comments on "Energy cost, mechanical work and muscular efficiency in swing
      through gait with elbow crutches".

PMID- 9239575
TI  - Development of targeted delivery systems for nucleic acid drugs.
AB  - Our increased understanding of disease pathogenesis is the basis for developing
      novel nucleic acid drugs. The main challenge encountered in this development is
      how to maintain therapeutically meaningful concentrations of the drugs in the
      vicinity of their targets for the desired periods. The intrinsic difficulty
      arises from the fact that nucleic acid drugs are not readily transported across
      membranes. Hence, their delivery and transport characteristics at the whole body,
      organ and cellular levels need to be thoroughly examined. Liposomes and receptor
      mediated polycation systems are promising carriers for their delivery in vivo.
      There are many barriers to be overcome for successful antisense and gene
      therapies. Along with other factors, disposition, stability against nucleases,
      binding to cell surface receptor and internalization, and intracellular
      trafficking affect the in vivo delivery and efficacy of nucleic acid drugs. This
      review article discusses the delivery and transport of these compounds.

PMID- 9239576
TI  - Derivatives of melphalan designed to enhance drug accumulation in cancer cells.
AB  - The objective of this study was to develop chemical strategies to improve the
      uptake and accumulation of melphalan (L-Mel and D-Mel), a cytotoxic agent, into
      cancer cells. Dipeptides synthesized from L- (or D-) Mel and L-glutamic acid (L
      Glu) or L-valine (L-Val) and their methyl or ethyl esters (all compounds were
      trifluoroacetic acid salts) were evaluated for cytotoxicity and cellular uptake
      using Caco-2 cells, a human colon carcinoma cell line, and RT-2 cells, a rat
      brain glioma cell line. Treatment of Caco-2 cells with L-Mel or D-Mel (0.5 mg/ml
      equivalent of melphalan) for 48 h resulted in approximately 50% cell survival.
      Treatment of the Caco-2 cells with dipeptide derivatives of L-Mel (or D-Mel) (11c
      d, 12c-d and 13) caused similar cytotoxicity effects (approximately 50-70% of
      cell survival). When the cytotoxicities of the esters of L-Mel, D-Mel and their
      dipeptide derivatives (11a-b, 12a-b and 14) in Caco-2 cells were determined, less
      than 10% cell survival was observed. Similar results were observed in RT-2 cells.
      When the cellular uptake properties of these compounds were determined in Caco-2
      cell monolayers, L-Glu-L-Mel (12c), L-Glu-D-Mel (12d), and L-Mel-L-Glu (11c)
      generated slightly lower intracellular levels of L-Mel or D-Mel than when the
      cell monolayer was treated with the amino acids (L-Mel or D-Mel). In Caco-2 cells
      treated with 11c, 12c or 12d, low levels of the dipeptides were also detected.
      Caco-2 cell monolayers treated with D-Mel-L-Glu (11d) or D-Mel-L-Val (13) showed
      very low levels of the amino acids (L-Mel or D-Mel), but generally higher levels
      of the dipeptides. In contrast to the amino acids (L-Mel, D-Mel) or the dipeptide
      derivatives (11c-d, 12c-d and 13), the ester derivatives of the amino acids [L
      Mel(OEt), D-Mel(OEt)] or the dipeptides (11a-b, 12a-b and 14) produced 5-20 times
      higher intracellular concentrations of potentially cytotoxic metabolites (e.g., L
      Mel, D-Mel, Mel-containing dipeptides or Mel-containing dipeptide monoesters). L
      Mel(OEt), D-Mel(OEt), L-Glu(OEt)-L-Mel(OEt) (12a), L-Glu(OEt)-D-Mel(OEt) (12b),
      and L-Mel-L-Glu(OEt)2 (11a) accumulated mainly as either L-Mel or D-Mel, and the
      percentages of L-Mel or D-Mel were 99%, 99%, 90%, 75% and 98% of the total
      intracellular concentration of potentially cytotoxic agents, respectively. D-Mel
      L-Glu(OEt)2 (11b) accumulated as its monoester (> 95%) and D-Mel-L-Val(OMe) (14)
      accumulated as its dipeptide metabolite (> 98%). Inclusion of Gly-Pro, carnosine,
      L-Phe or L-Glu did not inhibit uptake of the dipeptide derivatives of L-Mel (or D
      Mel) or their esters. These results suggest that the cellular uptake of the
      dipeptide derivatives of melphalan and their esters is probably via passive
      diffusion rather than being facilitated by an amino acid transporter or a
      di/tripeptide transporter. The higher intracellular levels of cytotoxic agents
      generated from the ester derivatives of the amino acids and the dipeptides are
      probably due to their higher lipophilicity and the overall neutral charge of the
      esters and subsequent intracellular formation of the more polar amino acids (L-
      or D-Mel) and/or Mel-containing dipeptides. Finally, these studies suggest that
      dipeptides of D-Mel [11b, 11d, 13] have inherent cytotoxicity properties.

PMID- 9239577
TI  - Preparation and evaluation of chitosan microspheres containing bisphosphonates.
AB  - Local implantation or injection of microspheres containing bisphosphonates for
      site-specific therapy may aid in treating several pathological conditions
      associated with bone destruction. Chitosan microspheres containing two
      antiresorption and anticalcification agents, pamidronate and
      suberoylbisphosphonate (SuBP), were prepared from a w/o emulsion. Various
      formulation variables were studied for their effect on the release rate profile
      of these bone-seeking agents. Polymer coating of micromatrices yielded
      microspheres with the most retarded release rate, and the drug delivery system
      was found biocompatible in endothelial cell culture. The microspheres were
      examined in vitro and in vivo for release kinetics and drug disposition. The
      release of bisphosphonate from the microspheres was faster in vitro than in vivo.
      Drug disposition following implantation of microspheres in the tibialis muscle
      resulted in a relatively increased disposition in the adjacent tibia while
      injection of drug solution in the tibialis muscle resulted in uniform disposition
      of the drug in the femorae and tibiae. Bisphosphonate released from chitosan
      microspheres effectively inhibited bioprosthetic tissue calcification in the rat
      subdermal model.

PMID- 9239579
TI  - Human serum albumin as a probe for protein adsorption to nanoparticles: relevance
      to biodistribution.
AB  - A range of poloxamers and poloxamines were adsorbed to biodegradable poly(lactide
      co-glycolide) (PLGA) and non-biodegradable polystyrene (PS) particulate systems
      in order to alter their surface characteristics and produce potential drug
      targeting systems. Human serum albumin (HSA) was chosen as a model protein to
      investigate protein adsorption to the above systems and was quantified by two
      techniques. I125 radiolabelled HSA proved to be a useful probe for determining
      protein adsorption but was limited by a modification that occurred on storage.
      Also, HSA eluted from the particle surface was quantified by densitometry
      following it's development on an SDS-PAGE gel. Both techniques produced similar
      results. For cleaned coated PS particles it was found that the PEO chain length
      and the molecular structure of the block copolymer were important in preventing
      protein adsorption. The presence of excess block copolymer in the uncleaned
      preparations resulted in further suppression of HSA adsorption, which was thought
      to be due to their detergent properties. Due to the different results obtained
      with similarly coated PLGA particles, it was concluded that the block copolymers
      adsorb onto the surface of the PLGA particles in a different conformation to
      those adsorbed onto PS particles. Correlating in vivo biodistribution in terms of
      the prevention of protein (opsonin) adsorption was of only limited success and it
      was concluded that adsorption data for a single model protein can only be used
      with caution to predict the in vivo behaviour of colloidal targeting systems.

PMID- 9239578
TI  - Block-copolymer of polyethylene glycol and polylysine as a carrier of organic
      iodine: design of long-circulating particulate contrast medium for X-ray computed
      tomography.
AB  - In order to obtain small, polymer-stabilized particulate carriers for organic
      iodine to serve as a contrast agent for X-ray computed tomography (CT) an attempt
      was made to design a carrier based on polymeric micelles. Here we describe the
      synthesis of an iodine-containing amphiphilic block-copolymer which can micellize
      in aqueous solutions. The two blocks of the copolymer consisted of
      methoxypoly(ethyleneglycol) and poly[epsilon,N-(triiodobenzoyl)-L-lysine]. Upon
      dispersion in water, the block copolymer formed particles with average diameter
      80 nm and iodine content up to 44.7%. The particles start to dissociate to the
      individual polymeric chains in the concentration range of 0.05-0.5 microM in
      water at 23 degrees C. Upon intravenous injection at 250 mg of iodine/kg (570 mg
      of the agent/kg) in rabbits the medium demonstrated exceptional 24 hr half-life
      in the blood substantiating corona/core structure of the particles with PEG
      chains protecting the iodine-containing core. The possible use of these
      particulates as contrast medium for X-ray computed tomography is discussed.

PMID- 9239580
TI  - Changes in oxygenation variables during progressive hypothermia in anesthetized
      patients.
AB  - Because deliberate hypothermia is becoming commonly used during neurosurgery,
      this study was performed to investigate the effects of a progressive reduction of
      body core temperature (T) on whole body oxygenation variables in patients
      undergoing elective intracranial surgery. In 13 patients (Hypothermic Group), T
      was reduced to 32.0 degrees C using convective-based surface cooling. In six
      patients (Control Group), T was maintained at 35.5 degrees C during the entire
      study period. The cardiac index (CI) was determined with a pulmonary artery
      catheter by thermodilution. Whole body oxygen delivery (DO2) was calculated from
      CI and arterial oxygen content. Whole body oxygen consumption (VO2), carbon
      dioxide production (VCO2), and energy expenditure (EE) were determined by
      ventilation gas analysis (indirect calorimetry). Mixed venous oxygen tension at
      50% saturated hemoglobin (P50), and whole body oxygen extraction ratio (O2ER)
      were calculated. Repeated-measures analysis of variance and the Mann-Whitney test
      were used for statistical analysis. Data are expressed as means +/- SD. VO2 (from
      100 +/- 13 to 77 +/- 11 ml.min-1.m-2), VCO2 (from 75 +/- 7 to 57 +/- 7 ml.min-1.
      m-2), EE (from 667 +/- 67 to 509 +/- 66 kcal.d-1.m-2), P50 (from 23.8 +/- 1.7 to
      20 +/- 0.9 mm Hg), and O2ER (from 0.29 +/- 0.05 to 0.22 +/- 0.03%) decreased
      significantly in the Hypothermic Group between 35.5 and 32.0 degrees C (p <
      0.05). None of these variables changed in the Control Group and at 32.0 degrees C
      VO2, VCO2, EE, P50, and O2ER were significantly lower in the Hypothermic Group
      than in the Control Group. DO2 remained unchanged in both groups. We conclude
      that progressive hypothermia in anesthetized patients reduces metabolic rate but
      does not change DO2. The significant decrease in O2ER may partly be related to a
      leftward shift of the oxyhemoglobin dissociation curve, as evidenced by the
      decrease in P50.

PMID- 9239581
TI  - Anesthesia for carotid endarterectomy: a survey.
AB  - Indications for carotid endarterectomy (CEA) have been expanded recently, and a
      consensus statement has been made regarding these changes. However, the debate
      regarding the "ideal" anesthetic for CEA remains on-going. This study was
      designed to evaluate the actual anesthetic techniques used by anesthesiologists
      for CEA. A total of 426 1-page questionnaires were mailed to all current (1995)
      members of the Society of Neurosurgical Anesthesia and Critical Care (SNACC). Of
      these, 216 (50.7%) were completed and returned. The majority of these respondents
      (84.7%) administered general anesthesia (GA) for CEA. Regional anesthesia (RA)
      was the anesthetic method of choice for 16.7%, whereas 2.8% each chose either
      local anesthesia (LOC) or a combined regional/general (RA/GA) technique. Despite
      the controversial role of nitrous oxide in neuroanesthesia, 74.6% of those
      returning the survey use nitrous oxide during CEA. Intraoperative neuromonitoring
      use was reported by 90% of the respondents, with the electroencephalography (EEG)
      the favored modality (67.5%). Specific intraoperative neuroprotective measures
      were provided by only 22.2% of all respondents, with barbiturates as the favorite
      method (50.0%). The technique of intraoperative hypertension is practiced by a
      majority of those surveyed (61.1%), with the most common target blood pressures
      being either preoperative baseline or preoperative baseline plus 20%. Although
      there is some trend towards nonintensive care setting for postoperative care, the
      intensive care remains the location of choice for overnight care of CEA patients
      (71.8%). The results of this study show that despite arguments for RA over GA,
      the majority of anesthesiologists surveyed choose GA for CEA.

PMID- 9239582
TI  - Research synthesis of controlled studies evaluating the effect of hypocapnia and
      airway protection on cerebral outcome.
AB  - Hyperventilation is a standard method of treating patients with intracranial
      hypertension. I reviewed all the relevant peer-reviewed literature to identify
      the documented benefits of hyperventilation as treatment for cerebral disease.
      Studies were identified by searches of the Medline database between 1966 and
      September 1996, interviews with experts, and reviews of reference lists. Retained
      manuscripts reported results of a human or animal controlled trial that tested
      effect of hyperventilation and/or systemic hypocapnia on mortality,
      histopathology, or neurologic examination. Studies could be either randomized or
      observational and need not have been blinded. I found that for no clinical
      studies of cerebral disease, other than in acute head injury patients, was there
      any suggestion of a clinical benefit from hyperventilation. Three controlled,
      observational studies examined effects of airway management and ventilatory
      support in head-injured patients. These studies found that maintaining such
      patients hypocapnic, versus spontaneously breathing without ventilatory support,
      decreased mortality. However, by design the studies could not establish whether
      hypocapnia itself contributed to the decreased mortality. Two clinical studies
      examined the effect of PaCO2 itself in patients with head injury. In both,
      hypocapnic patients did not have better neurologic outcome. In conclusion,
      securing the airway and supporting ventilation probably reduces mortality in
      unconscious, neurosurgical patients. However, there are virtually no clinical
      data that hypocapnia improves outcome in patients with cerebral disease.

PMID- 9239583
TI  - The effects of fentanyl and sufentanil on cerebral hemodynamics.
AB  - Our study investigated the effects of moderate doses of fentanyl and sufentanil
      versus high-dose sufentanil on cerebral hemodynamics by using transcranial
      Doppler ultrasonography (TCD). Thirty American Society of Anesthesiologists (ASA)
      II and III patients scheduled for elective coronary artery bypass graft (CABG)
      were studied after Institutional Review Board (IRB) approval and informed
      consent. The evening before surgery, all patients received oral flurazepam (1
      mg/kg), Atropine (0.4 mg/70 kg s.c.) and a combination of droperidol (70
      micrograms/kg s.c.) plus fentanyl (1.5 micrograms/kg s.c.) were given as
      preanesthetic medication 1 h before induction of anesthesia. Anesthesia was
      induced with either 25 micrograms/kg fentanyl i.v. (group 1, n = 10), 3
      micrograms/kg sufentanil i.v. (group 2, n = 10) or 6 micrograms/kg sufentanil
      i.v. (group 3, n = 10). All patients received 100 micrograms/kg pancuronium i.v.
      With the induction of respiratory depression, assisted ventilation was performed
      followed by controlled ventilation to maintain normoxia and normocapnia (FiO2,
      1.0). Cerebral blood flow velocity (CBFV, cm/s) was measured continuously in the
      middle cerebral artery by using a bidirectional 2-MHz TCD system. Monitoring
      included heart rate (HR, beats/min), direct mean arterial blood pressure (MAP, mm
      Hg), and PaCO2. Physiologic variables including arterial blood gases were
      measured at baseline, 5 min, and 10 min after infusion of fentanyl or sufentanil.
      In all patients, HR, MAP, end-tidal carbon dioxide tension (PetCO2), and PaCO2
      were constant over time and did not differ between groups. CBFV did not change
      with moderate doses of fentanyl (group 1) or sufentanil (group 2). In contrast,
      infusion of high-dose sufentanil (group 3) was associated with 27 to 30%
      decreases in CBFV (p < 0.05). Our results suggest that sufentanil decreases CBFV
      in a dose-related fashion with a threshold effect. Increases in CBFV and CBF seen
      in previous studies may be related to an increasing PaCO2 when maintenance of
      normocarbia is based on only real-time capnography with a constant PetCo2 rather
      than additional arterial blood gas monitoring.

PMID- 9239584
TI  - The use of ketamine or etomidate to supplement sufentanil/N2O anesthesia does not
      disrupt monitoring of myogenic transcranial motor evoked responses.
AB  - Intraoperative monitoring of myogenic transcranial motor evoked responses (tc
      MERs) requires an anesthetic technique that minimally depresses response
      amplitudes. Acceptable results have been obtained during opioid/N2O anesthesia,
      provided that the concentration of N2O does not exceed 50%. However, this
      technique may necessitate supplementation with additional agents to achieve
      adequate depth of anesthesia. Etomidate and ketamine have been reported
      anecdotally or in nonsurgical situations to produce little tc-MER depression. We
      investigated the effects on tc-MER amplitude and latency of supplementation of a
      sufentanil/N2O anesthetic with etomidate or ketamine in patients undergoing
      spinal instrumentation. Anesthesia was induced with etomidate 0.3 mg/kg and
      sufentanil 1.5 mg/kg and maintained with sufentanil 0.5 mg/kg/h and N2O 50%.
      Muscle relaxation was kept at 25% of control. Paired transcranial electrical
      stimulation was performed. Each patient randomly received either ketamine (0.5
      mg/kg) or etomidate (0.1 mg/kg) as a single bolus intravenously, during stable
      surgical conditions. Triplicate tc-MERs were recorded from the tibialis anterior
      muscles before and 2, 5, 10, and 15 min after drug administration. Administration
      of ketamine did not significantly change tc-MER amplitudes, whereas etomidate
      resulted in a transient amplitude depression to 72% of control (p < 0.05) at 2
      min after injection. Latency remained unchanged with both drugs. In conclusion,
      the data suggest that both ketamine (0.5 mg/kg) and etomidate (0.1 mg/kg) can be
      used to supplement sufentanil/N2O anesthetic without disrupting tc-MER
      monitoring.

PMID- 9239585
TI  - Increase in antioxidant capacity of plasma during propofol anesthesia.
AB  - We have examined the effect of total intravenous anesthesia (TIVA) using a
      continuous propofol infusion on the antioxidant capacity of plasma in 18
      neurosurgical patients who required cerebrospinal fluid shunting. Patients were
      premedicated with hydroxyzine, alprazolam, and atropine. Anesthesia was induced
      intravenously with propofol 1.5 mg kg-1 and sufentanil 0.15-0.3 microgram kg-1.
      Tracheal intubation was facilitated with atracurium 0.5 mg kg-1. Anesthesia was
      maintained with a continuous propofol infusion at an increasing rate from 6 to 12
      mg kg-1 h-1 under controlled ventilation (FiO2 = 0.4 in air). In all patients,
      arterial blood samples were drawn before induction of anesthesia and during
      surgery for measurement of blood propofol concentration and plasma antioxidant
      capacity, which was assessed as the ability to inhibit lipid peroxidation. Lipid
      peroxidation was induced in vitro by exposing a linoleic acid microemulsion to
      hemoglobin-generated oxoferryl radicals, and assessed by ultraweak
      chemiluminescence in the absence (control) and the presence of the plasma
      samples. The antioxidant capacity of plasma, measured by the inhibition of light
      emission and expressed as a percentage of control, increased significantly from
      39.8 +/- 2% (mean +/- SEM) to 44.7 +/- 2.4% during anesthesia (Wilcoxon test, p <
      0.001). No correlation was observed between this increased resistance to lipid
      peroxidation and blood propofol concentrations (Spearman test, r = 0.07, NS). We
      conclude that the capacity of plasma to inhibit lipid peroxidation increases in
      patients during TIVA maintained with a continuous propofol infusion.

PMID- 9239586
TI  - Patient-controlled sedation using propofol during interventional neuroradiologic
      procedures.
AB  - Patient-controlled sedation (PCS) using propofol has been reported to provide
      safe and effective sedation during a variety of procedures performed under
      regional or local anesthesia. In a prospective, randomized fashion, this study
      evaluated propofol PCS compared to anesthesiologist-administered midazolam
      fentanyl sedation during interventional neuroradiologic (INR) procedures.
      Nineteen patients undergoing 24 INR procedures received propofol PCS (PCS dose,
      0.5 mg/kg; lockout interval, 3 min) or anesthesiologist-administered midazolam
      fentanyl sedation. Study parameters included discomfort, sedation and anxiety
      visual analogue scores (VAS), cognitive function, patient satisfaction, and
      complications. No difference was found between the two sedation techniques with
      respect to the levels of sedation and anxiolysis. Cognitive function was well
      preserved in both groups. Patient satisfaction was similarly high in both groups.
      Complications were similar between groups. These included ventilatory depression
      (two patients in each group) and excessive sedation (two patients in each group).
      Three patients in the propofol group became excessively restless, resulting in
      brief interruptions during the respective procedures. Propofol PCS offers a safe
      sedation technique during INR procedures with a sedation and anxiolysis profile
      that was not distinguishable from anesthesiologist-administered midazolam
      fentanyl sedation.

PMID- 9239587
TI  - Computer-controlled infusion of propofol for long neurosurgical procedures.
AB  - This study evaluated the performance of a computer-controlled infusion (CCI)
      system for propofol during long neurosurgical procedures. Anesthesia was induced
      and maintained in 15 patients using a CCI of propofol. The initial target
      concentration was set at 3 micrograms/ml, and this was then titrated according to
      the clinical situation. A total of 284 blood samples were taken for propofol
      assay. The performance of the system during anesthesia, assessed using the median
      performance error (MDPE), median absolute performance error (MDAPE), wobble, and
      divergence, were -5.3%, 20.6%, 9.0%, and 0.3%/h, respectively. MDPE and MDAPE
      during the first 20 min after stopping the infusion were -38.7% and 39.0%,
      respectively. The CCI system did not show significant changes in predictive
      ability, with time during anesthesia lasting up to 12 h. Changes in the measured
      blood concentration were in the same direction as changes in the target
      concentration.

PMID- 9239588
TI  - Convection versus conduction cooling for induction of mild hypothermia during
      neurovascular procedures in adults.
AB  - Hypothermia for cerebral protection is usually achieved by administration of
      intravenous fluids at room temperature, cooling ambient air, ice packs, and a
      temperature-adjustable circulating water mattress. We compared cooling by
      conduction by using a water mattress to cool by convection by using a forced-air
      cooling device. Twenty patients were prospectively randomized to two groups: 10
      patients cooled by convection (CC) and 10 patients cooled by traditional methods
      (TC). Two patients in the CC group were withdrawn from the study and excluded
      from the analysis; one patient for failure to cool despite the use of both
      techniques, and the other for the abrupt onset of arrhythmias and myocardial
      depression during hypothermia. Temperature was measured at the tympanic membrane,
      pulmonary artery, and esophageal probe sites and recorded every 15 min. The time
      required to reach the target temperature range of 33-34 degrees C was recorded.
      We found no differences in the temperatures measured at the three sites during
      cooling and rewarming. Baseline temperatures recorded from the pulmonary artery
      catheter before beginning "active cooling" were similar in both groups (TC, 35.0
      +/- 0.2 degrees C vs. CC, 35.3 +/- 0.1 degrees C). We found no difference in the
      time to target temperature between TC and CC (TC, 178 +/- 25 min vs. CC, 142 +/-
      21 min). One patient had some arrhythmias on cooling in the convective group, but
      her preoperative condition may have been responsible. In conclusion, cooling by
      convection appears to be a safe alternative to conduction cooling.

PMID- 9239589
TI  - Cerebral arteriovenous PCO2 difference and early global cerebral ischemia in a
      patient with acute severe head injury.
AB  - We report a case of acute head injury with severe diffuse brain swelling in which
      early global cerebral ischemia was followed by brain death. Global cerebral
      ischemia was detected by cerebral arteriovenous lactate content difference,
      cerebral arteriovenous carbon dioxide tension (PCO2) difference, and cerebral
      arteriovenous hydrogen ion content difference. Physiopathological aspects of
      cerebrovenous hypercarbia are discussed.

PMID- 9239590
TI  - Incidence and predictors of bulbar palsy after surgery for acoustic neuroma.
AB  - We present a retrospective review of the perioperative management and
      complications of 102 cases of acoustic neuroma operated on at an English teaching
      hospital over the last 9 years. Nine patients had a bulbar palsy postoperatively;
      five of those patients developed pulmonary complications. A bulbar palsy was more
      likely to occur in those with tumours > or = 3 cm. The occurrence of
      intraoperative bradycardias, present in nearly half of the bulbar palsy cases,
      did not help predict who would sustain this injury postoperatively. However,
      episodes of intraoperative hypotension served to better predict a bulbar palsy
      complication in conjunction with the presence of a large tumour. Post-operative
      airway management is an area of possible conflict of interest: the desire for
      early extubation to avoid the possibility of coughing and bucking on the
      endotracheal tube and the need to protect the airway of the patient with a lower
      cranial nerve deficit. Almost 10% of our patients did have such a deficit after
      surgery; and over half of them developed respiratory complications making this an
      important cause of postoperative morbidity. We recommend that the timing of
      extubation be judged on an individual basis for each patient. Those with tumours
      > or = 3 cm warrant particular concern. All patients should receive careful
      observation in a high dependency area for at least the first postoperative day.

PMID- 9239591
TI  - Electrographic tachyphylaxis to etomidate and ketamine used for refractory status
      epilepticus controlled with isoflurane.
AB  - Etomidate and ketamine controlled seizures but acute tachyphylaxis occurred.
      Isoflurane was then used to control seizures.

PMID- 9239592
TI  - Management of swallowing disorders and chronic aspiration by glottic closure
      procedure.
AB  - We report an 18-year-old man with a posterior fossa tumor who had to undergo a
      partial resection of the tumor and supportive radiation therapy. Functional
      deficits of the lower cranial nerves, particularly the glossopharyngeal and vagal
      nerves, associated with severe swallowing disorders and refractory aspiration
      pneumonia were seen postoperatively. The admission to the intensive care unit
      (ICU) resulted from increasing respiratory failure accompanied by recurrent
      septic episodes. Nutritional support via nasogastric tube and later percutaneous
      endoscopic gastrostomy (PEG) were hampered by complications such as persistent
      sinusitis, local dermatitis surrounding the entrance of the PEG tube, and the
      development of duodenal ulcers. Furthermore, the use of continuous subglottic
      aspiration failed to prevent pulmonary infections. After a 9-week stay in the ICU
      due to inadequate antimicrobial therapy of aspiration pneumonia and the patient's
      persistent sepsis, a temporary surgical separation of airway and food passages
      was performed by glottic closure. Subsequently chronic aspiration stopped, and 3
      months after admission to the ICU, the patient had stable vital organ function
      and was transferred to a surgical ward free of infections. Glottic closure was
      reversed successfully 7 months later. When compared with laryngeal function on
      admission, there was no more impairment. Thus, temporary glottic closure seems to
      be an efficacious treatment to prevent life-threatening septic complications in
      patients with refractory aspiration pneumonia.

PMID- 9239593
TI  - Inflammatory reactions of the skin caused by adhesive EEG electrodes.
AB  - The correct choice of electrodes for neurophysiologic monitoring is one of the
      unsolved problems in clinical practice and scientific research. In addition to
      the familiar electrodes, i.e., cup (silver-/silver-chloride, gold) and needle
      electrodes, adhesive electrodes (e.g., Zipprep electrodes) have been offered for
      rapid application and accurate signal recording. This case report indicates that
      adhesive electrodes can lead to superficial lesions of the skin or inflammatory
      infiltration.

PMID- 9239595
TI  - Late modification of tracheal wall after percutaneous tracheostomy: a likely
      hazard due to a paramedian access.

PMID- 9239594
TI  - The effect of isoflurane on biochemical changes during and electrophysiological
      recovery after anoxia in rat hippocampal slices.
AB  - It is unclear whether isoflurane protects against neuronal damage. This study
      examines the extent and mechanism by which isoflurane might affect anoxic
      neuronal damage. The size of the evoked postsynaptic population spike recorded
      from the CA 1 pyramidal cell layer of the rat hippocampal slice 60 min after
      anoxia was compared with its preanoxic, preisoflurane level. Intracellular
      adenosine triphosphate (ATP), sodium, and potassium levels were measured in the
      dentate and CA 1 regions at the end of the anoxic period in similarly treated
      slices. Isoflurane increased the latency and reduced the amplitude of the evoked
      response before anoxia. Isoflurane (2%) did not significantly improve recovery of
      the evoked response after 5 min of anoxia (untreated slices = 6 +/- 2% (mean +/-
      SEM), isoflurane = 17 +/- 7%); 1.5% isoflurane also did not significantly improve
      recovery after 4 min of anoxia (untreated = 30 +/- 8% vs. 1.5% isoflurane = 47 +/
      12%). Isoflurane did not significantly attenuate the decrease in ATP levels in
      either the dentate or CA 1 regions of the hippocampal slice during 4 or 7 min of
      anoxia; however, there was a significant improvement in ATP levels after 10 min
      of anoxia in both regions of isoflurane-treated preparations (1.0 +/- 0.1 vs. 1.4
      +/- 0.1, CA 1; 1.3 +/- 0.1 vs. 2.0 +/- 0.2 nM/mg dry weight, dentate). Sodium
      concentrations increased and potassium concentrations decreased during anoxia.
      Isoflurane did not significantly attenuate the changes in these ions during
      anoxia. In conclusion, isoflurane does not significantly improve recovery of CA 1
      pyramidal cells during anoxia nor does it attenuate the anoxic changes in ATP,
      sodium, and potassium after 4 or 7 min of anoxia. With a more prolonged period of
      anoxia (10 min) isoflurane reduces the decrease in ATP levels.

PMID- 9239596
TI  - Age-specific competencies.

PMID- 9239597
TI  - A brief history of positron emission tomography.
AB  - Shortly before the time of this writing, Michael Ter-Pogossian, PhD, passed away
      at the age of 71. He was considered by many to be the father of PET and is best
      known for experiments beginning in the 1950s, which led to the development of PET
      as a practical diagnostic tool (Fig. 1). In my research of the literature for
      this article, Dr. Ter-Pogossian's name appeared frequently on many of the
      landmark publications and I have drawn heavily from his work as a historian and
      scientist. His death is a great loss to the nuclear medicine community. It is
      with his achievements in mind, as well as the achievements of many other
      outstanding scientists, that I have written this article. I have tried to be as
      accurate as possible in my documentation of events as well as in my
      interpretation of their significance. I trust that the reader will gain as much
      as I have from this endeavor.

PMID- 9239598
TI  - Radiation safety review for 511-keV emitters in nuclear medicine.
AB  - With the advent of high-energy collimators and dual-head coincidence cameras,
      standard nuclear medicine facilities will soon begin imaging with PET isotopes.
      The use of 511-keV emitters raises new radiation safety concerns for
      technologists traditionally limited to handling 99mTc and other low-energy
      isotopes. This article is a basic review of positron emitters, measurement
      concerns, exposure rates, shielding requirements and external radiation exposure
      mitigation. Newly developed PET shielding products are presented and regulatory
      status is discussed briefly.

PMID- 9239599
TI  - Cancer imaging with radiolabeled antibodies: new advances with technetium-99m
      labeled monoclonal antibody Fab' fragments, especially CEA-Scan and prospects for
      therapy.
AB  - The use of radiolabeled anticancer antibodies to detect cancer sites by external
      scintigraphy has had a relatively long history. With the advent of monoclonal
      antibodies (MAbs), which precluded the need for purifying the antibodies by
      laborious purification steps, there was a surge of interest and efforts to
      develop these reagents for both imaging and therapy applications (1). Today, many
      thousands of patients have received different forms and doses of MAbs for various
      purposes, and four MAb-based products have been licensed for manufacture and sale
      in the U.S. (2,3). This article describes the most recent MAb product to be
      approved in the U.S. for colorectal cancer imaging, including discussions of
      using this agent and its therapeutic counterpart in several cancer types.

PMID- 9239600
TI  - Caring for the older patient, Part I: The relationship of theory to practice.
AB  - This is the first article of a four-part series on gerontology and its
      applications to the care of elderly patients in nuclear medicine. The series
      includes discussions about the theories of aging, approaches to meeting the
      special needs of the elderly and ethical dilemmas in caring for the elderly. It
      also reviews anatomical and physiological changes associated with aging and the
      role of nuclear medicine studies in caring for the elderly. Upon completion of
      this article, the reader should be able to: (a) describe the aging U.S.
      population by citing demographic data; (b) identify the theories of aging and
      distinguish their major characteristics; (c) differentiate a gerontologic
      approach from a geriatric approach in caring for the elderly; and (d) recognize
      factors important to the delivery of effective care for the elderly.

PMID- 9239601
TI  - Clinical comparison of circular versus noncircular acquisition using technetium
      99m myocardial perfusion SPECT imaging.
AB  - The optimal orbit for myocardial SPECT imaging has not yet been determined. In
      order to evaluate differences in image quality and reader interpretation between
      orbiting methods, 50 patients scheduled for routine stress/rest 99mTc-sestamibi
      imaging had both a circular and a noncircular study using an ADAC Vertex dual
      head imaging system. METHODS: Each study was acquired using a 64 x 64 matrix, 64
      stops at 25 sec per stop. Images were processed using a Butterworth filter with a
      frequency cutoff of 0.6 and an order of 5.0. Studies were interpreted by three
      experienced readers without knowledge of patient name or orbiting technique for
      normal and abnormal segments and overall image quality. RESULTS: There was no
      significant difference in the semi-quantitative assessment of either defect
      extent or reversibility or in the quantitative assessment of defect size between
      the two types of orbits. However, while all 50 noncircular studies were read as
      good or fair quality, 23 circular studies were read as fair or poor (p = <
      0.0002). CONCLUSION: Qualitative and quantitative analysis revealed similar size
      and extent of perfusion defects using either circular or noncircular orbit, but
      images with the noncircular orbit were of significantly better image quality and
      may be preferable to a circular orbit with 99mTc-sestamibi.

PMID- 9239602
TI  - Nonuniformity intrinsic flood artifact caused by point-source syringe needle.
AB  - The purpose of this study was to investigate the cause of a nonuniformity
      artifact seen on an intrinsic flood. METHODS: Intrinsic floods were acquired on
      three different cameras using a point source in a 1-cc syringe, with and without
      a needle attached. Floods were obtained with the syringe placed perpendicular and
      parallel to the camera face. RESULTS: A nonuniformity artifact was evident if a
      syringe with a needle was placed perpendicular to the crystal face. CONCLUSION:
      If a syringe is used as a point source during the acquisition of an intrinsic
      quality control flood, the needle should not be placed perpendicular to the
      camera face.

PMID- 9239603
TI  - Ultratag RBC kit for combined cardiac first-pass and multigated acquisition
      studies.
AB  - The authors developed a procedure to use the in vitro Ultratag (Mallinckrodt, St.
      Louis, MO) red blood cell (RBC) labeling kit for both first-pass (FP) and
      multigated acquisition (MUGA) studies with a high specific activity in a reduced
      volume (50 mCi/0.5 ml) and a high labeling efficiency that can be used with a
      single-crystal camera to yield a quality study. METHODS: A packed red blood cell
      (PRBC) bolus was created by two methods: (a) reducing the volume of the
      components of the Ultratag kit and (b) centrifuging the final dose volume. The
      labeling efficiency of each bolus was evaluated, each PRBC bolus was visually
      inspected for clots and percent hemolysis was assessed using a hemocytometer at
      30 min, 1 hr and 2 hr postcentrifugation. RESULTS: Use of the first method, the
      50% kit, provided the best results. However, the resulting volume from this kit
      only approached 1 ml, which is not clinically adequate for a first-pass study. In
      the second method, the total volume was centrifuged to form a PRBC bolus, which
      appeared to be stable in the syringe for at least 2 hr. A combined FP/MUGA study
      from a centrifuged 50% reduced kit was performed in one normal subject as a
      preliminary assessment of the clinical utility of this procedure. The image
      quality of the scan is diagnostically adequate. CONCLUSION: By using the in vitro
      Ultratag kit, a compact PRBC bolus was created that was stable in the syringe and
      could be reinjected safely into the patient for combined cardiac FP/MUGA studies.

PMID- 9239604
TI  - A rapid chromatographic method for quality control of technetium-99m-bicisate.
AB  - The purpose of this work was to develop a simple and rapid method to determine
      the radiochemical purity of 99mTc-bicisate. METHODS: A rapid paper
      chromatographic (PC) method was developed to determine the radiochemical purity
      of 99mTc-bicisate and compare the results with those of the manufacturer's
      recommended method. The present PC method included Whatman 3MM paper as the solid
      phase and ethyl acetate as the solvent. RESULTS: The time for chromatography by
      this technique was 4-5 min compared to about 23 min by the manufacturer's method.
      The Rf value of 99mTc-bicisate (Rf = 0.9-1.0) was widely different from those of
      99mTcO4- and reduced 99mTc (Rf = 0.0 for both) so the chromatographic strip after
      development could be readily cut into two segments, in order to determine the
      labeling yield. CONCLUSION: No significant difference in labeling yields was
      found between the present method and the manufacturer's method. The PC method
      using Whatman 3MM paper and ethyl acetate is a simple and fast technique to
      determine the radiochemical purity of 99mTc-bicisate and may be substituted for
      the manufacturer's recommended method to save time.

PMID- 9239605
TI  - Rapid miniaturized chromatography for technetium-99m-tetrofosmin.
AB  - The purpose of this investigation was to develop and evaluate a new and rapid
      miniaturized chromatography system that would accurately assess the radiochemical
      purity of 99mTc-tetrofosmin without the problems of solvent ratios and time
      requirements associated with the manufacturer's recommended procedure. METHODS:
      The migration of the radiochemical components of 99mTc-tetrofosmin was evaluated
      using various chromatography media with ethyl acetate as the solvent. After
      optimization of the miniaturized system, radiochemical purity assessments were
      performed simultaneously on 23 99mTc-tetrofosmin preparations using both
      recommended and miniaturized chromatography systems. RESULTS: A miniaturized
      chromatography system consisting of Whatman 1 chromatography paper with ethyl
      acetate was developed for the radiochemical purity assessment of 99mTc
      tetrofosmin. Radiochemical purity results for 99mTc-tetrofosmin preparations were
      similar with both recommended and miniaturized chromatography methods, with a
      mean difference of 1.5% +/- 1.2% (s.d.). Differences in radiochemical purity
      results between the two chromatography systems were less than 2% (20 of 23
      evaluations) with most preparations. CONCLUSION: Radiochemical purity results for
      99mTc-tetrofosmin preparations were similar with both the manufacturer's
      recommended chromatography and miniaturized chromatography systems. The
      miniaturized chromatography system is easier to use, and the time required to
      perform radiochemical purity assessments is substantially reduced.

PMID- 9239606
TI  - Esophageal passage of iodine-131 capsules.
AB  - The purpose of this study was to determine the orogastric transit time of
      standard 131I capsules and the incidence of transit delay. METHODS: We studied 58
      consecutive subjects receiving outpatient diagnostic and therapeutic 131I
      dosages. A standard ion chamber survey meter, placed over the left upper quadrant
      of the abdomen, monitored orogastric transit. Each subject had ample water to
      subjectively swallow their capsule. Orogastric transit times, volume of water
      ingested, capsule size, and demographic and historical data were recorded for
      each subject. RESULTS: Seventeen subjects (29%) had delayed transit, with an
      orogastric transit time > 90 sec (median 140 sec, range 100-930 sec). Forty-one
      subjects had normal transit (median 14 sec, range 4-51 sec). We identified
      delayed transit in 7 of 37 women (19%) and 10 of 21 men (48%) (p = 0.035). Age,
      capsule size and initial water volume ingested did not differ significantly
      between subject groups. CONCLUSION: Men were more likely than women to have
      prolonged orogastric transit of standard 131I capsules. Other than sex, we found
      no identifiable clinical feature or medical history to predict delayed orogastric
      transit. A standard survey meter can identify adherent capsules to minimize
      esophageal radiation exposure.

PMID- 9239607
TI  - Parathyroid scintigraphy.
AB  - Scintigraphy of the parathyroid glands continues to be controversial from several
      standpoints, including radiopharmaceutical choice, imaging protocol, results, and
      utility in clinical situations. This article reviews: the anatomy, physiology and
      pathology of the parathyroid glands; mechanisms of radiopharmaceutical
      localization; commonly accepted imaging protocols; image results; and the
      appropriate use of parathyroid scintigraphy.

PMID- 9239608
TI  - Development of oncology protocol using fluorine-18-FDG: one center's experience.
AB  - The major types of cancer studied at the authors' facility were colorectal (107
      patients), head and neck (122 patients), gastric/esophageal (57 patients), lung
      (59 patients) and lymphoma (26 patients). This article presents guidelines and
      techniques for obtaining optimal PET studies. The authors devised these
      guidelines through trial and error and hope that by sharing them other facilities
      can avoid unnecessary mistakes and achieve better quality studies more
      efficiently.

PMID- 9239609
TI  - The effect of cyclosporine concentration on the labeling efficiency of an in
      vitro technetium-99m red blood cell labeling procedure.

PMID- 9239610
TI  - NMTCB directions.

PMID- 9239612
TI  - Radiation safety considerations for PET centers.
AB  - This article explains why technologists handling positron-emitting radionuclides
      may have higher measured radiation exposures than technologists working with
      single-photon emitting radionuclides. We will summarize measurements we have
      made, as well as those reported by other authors. In addition, we will describe
      the procedures implemented to minimize exposure.

PMID- 9239611
TI  - Caring for the older patient, Part II: Age-related anatomic and physiologic
      changes and pathologies.
AB  - This is the second article of a four-part series on gerontology and its
      applications to the care of elderly patients in nuclear medicine. This article
      reviews anatomic and physiologic changes and pathology associated with aging. It
      also discusses tailoring nuclear medicine procedures according to patients' needs
      and conditions, as well as adopting changes within the nuclear medicine
      department to better serve older patients. Upon completion of this article, the
      reader should be able to: (a) describe normal age-related anatomic and
      physiologic changes that are observed in older patients; (b) identify common age
      related disorders; (c) discuss considerations in tailoring nuclear medicine
      procedures for older patients; and (d) identify changes in the nuclear medicine
      facility that would better accommodate older patients.

PMID- 9239613
TI  - Utility and reproducibility of semiquantitative analysis of sestamibi breast
      images.
AB  - Technetium-99m-sestamibi scintimammography has been shown to be a useful
      diagnostic test in the detection of breast cancer. The purpose of this study was
      two-fold to: (a) evaluate semiquantitative indices of tracer uptake in lesions
      and determine if they are helpful in distinguishing benign from malignant breast
      lesions; and (b) test the reproducibility of these measures of sestamibi uptake
      in breast images. METHODS: Prone lateral planar imaging was performed on 27
      patients after intravenous injection of 20-30 mCi 99mTc-sestamibi. Data were
      analyzed by creating three regions of interest (ROIs) over designated areas:
      lesion, normal breast and right chest wall. Lesion-to-normal (L:N) and lesion-to
      chest wall (L:CW) ratios were calculated for each patient. Reproducibility was
      assessed by having two independent observers draw ROIs (interobserver) and one
      observer draw two independent sets of ROIs (intraobserver). RESULTS: L:N and L:CW
      ratios were significantly different for malignant versus benign lesions (p <
      0.001 for both ratios). Intraobserver and interobserver reproducibility showed
      good correlation with r = 0.98 (L:CW ratio). CONCLUSION: Semiquantitative
      analysis of sestamibi breast imaging results in reproducible uptake ratios that
      may be helpful in objectively interpreting imaging results.

PMID- 9239614
TI  - Determination of glomerular filtration rate using technetium-99m-DTPA with
      differing degrees of renal function.
AB  - Glomerular filtration rate (GFR) is an important index of renal function. Twenty
      four-hour creatinine clearance overestimates GFR in patients with poor renal
      function. Inulin and iothalamate clearances are accepted reference standards for
      determining GFR but are expensive and laborious. We have previously reported that
      GFRs obtained by measuring the disappearance of 99mTc-DTPA from ultrafiltered
      (protein-free) samples of plasma were virtually identical to those obtained by
      the iothalamate method. However, the subjects used in that study had normal to
      only moderately decreased renal function. METHODS: The accuracy of measuring GFR
      by plasma clearance of 99mTc-DTPA was determined in subjects where renal function
      varied from normal to severely impaired. In all subjects, GFR was established by
      clearance of 125I-iothalamate from urine and serum and was used as the standard
      of reference. RESULTS: For subjects with normal to moderately diminished renal
      function (GFR > 20 ml/min), the correlation between values of GFR obtained by the
      DTPA and iothalamate methods was high (n = 18, r = 0.966). The difference between
      the pairs of GFR values obtained by the two methods was not statistically
      significant (p > 0.1). In patients with severe renal insufficiency (GFR < 20
      ml/min), the correlation between the DTPA and iothalamate methods was poor (n =
      11, r = 0.236), and the GFR values obtained by the two methods were statistically
      different (p < 0.01). CONCLUSION: These results suggest that GFR can be
      determined accurately by plasma clearance of 99mTc-DTPA in all patients except
      those with severe renal insufficiency.

PMID- 9239615
TI  - Technical improvements in fluorine-18-FDG PET imaging of the abdomen and pelvis.
AB  - PET tumor imaging of the abdomen and pelvis is prone to artifacts due to urinary
      tract activity. A new technique has been developed to reduce such artifacts and
      enhance study interpretation. METHODS: Thirty minutes after the injection of 18F
      FDG, 500 cc 0.45% NaCl were administered intravenously over 30 min and a Foley
      catheter was placed in the bladder. At the start of imaging (60 min post
      injection), furosemide was given (0.3 mg/kg). Prior to imaging the pelvis, the
      urinary catheter was clamped and saline was introduced retrograde into the
      bladder until full. RESULTS: This technique has been used successfully in more
      than 130 patients, resulting in a marked improvement in study quality and tumor
      detection. CONCLUSION: Hydration and administration of furosemide, along with
      placement of a Foley catheter in the bladder, have proven effective in
      eliminating image artifacts originating from the kidneys, ureters and bladder.
      Backfilling the bladder also provides a well-defined anatomic landmark for study
      interpretation.

PMID- 9239617
TI  - Technologists plan for nuclear medicine's future.

PMID- 9239616
TI  - Dichotomous thinking in nuclear medicine technology.
AB  - Dichotomous thinking is the natural human tendency to think in a binary manner
      (either-or). Although it is natural, dichotomous thinking can be simplistic and
      may lead to a lack of consideration of alternatives. In nuclear medicine, a
      predominant use of dichotomous thinking can lead to a very elementary way of
      thinking that may produce technologists who do not question why or how things are
      done. Adaptation and survival in today's health care environment require complex
      ways of thinking. This article describes dichotomous thinking and its problems
      and pitfalls in nuclear medicine practice and education, and suggests that
      dichotomous thinking can be extended to dialectical (contradictory ideas) modes
      of thinking.

PMID- 9239618
TI  - An evolution of exercise physiology: effects of exercise on functional
      independence with aging and physical disabilities.

PMID- 9239619
TI  - 3-D imaging of residual limbs using ultrasound.
AB  - In this article, a method of using ultrasound to image a residual limb is
      presented. The method employs a compound scanning technique to reconstruct a
      cross-sectional image (a slice) of the limb in a transverse plane. By scanning
      the limb in many transverse planes, a three-dimensional (3-D) volumetric image
      can be obtained from which either a transverse slice, a longitudinal cross
      section, or a 3-D surface of the limb can be displayed. The compound process
      circumvents the problems associated with the large attenuation of bones and
      enables reconstruction of a complete image of bones and adjoining tissues. In
      addition, the compound process improves the lateral resolution and reduces the
      speckle noise. Results obtained from a pair of thin wires, a contrast-resolution
      phantom, and a human limb demonstrate the beneficial effects of the compound
      process. To maximize the benefits, however, an accurate pixel registration in
      image reconstruction is essential. Sources of pixel misregistration and the
      potential means of minimizing misregistration are discussed.

PMID- 9239620
TI  - Instantaneous centers of rotation in dorsi/plantar flexion movements of posterior
      type plastic ankle-foot orthoses.
AB  - Hingeless plastic ankle-foot orthoses (PAFOs) achieve ankle motion by flexing
      about the ankle joint. Instantaneous centers of rotation (ICRs) in dorsi- and
      plantarflexion movements, used as a measure of PAFO axes of movement, were
      measured to evaluate their fit to ankle motion. Thirty different PAFOs were
      fabricated and their stiffness modified in three stages. They were dorsi- and
      plantarflexed 16 degrees at 2 degrees-intervals using an original device.
      Displacement of two marks on the lateral calf-cuff were traced photographically,
      and ICRs were determined by plotting intersections of vertical bisectors for each
      displacement. The ICRs converged on the junction between the calf shell and the
      shoe insert. They deviated posteriorly from the anatomical ankle axis and caused
      the calf-cuff to move up-down during dorsi- and plantarflexion movements.
      However, this poor fit of the PAFO to ankle motion can be sufficiently
      compensated for by fastening straps more loosely.

PMID- 9239621
TI  - Mechanical advantage in wheelchair lever propulsion: effect on physical strain
      and efficiency.
AB  - In this experimental study on a prototype lever-propelled wheelchair, the effect
      of a range of mechanical advantages (MA) on physical strain, oxygen uptake,
      energy cost, mechanical efficiency, stroke frequency and perceived exertion was
      examined. Nine out of 10 male nonwheelchair users successfully performed five
      submaximal tests on a motor-driven treadmill in a prototype bi-manual
      asynchronous lever-propelled tricycle. Each test contained the same protocol, but
      made use of one of the five different MAs. In every test the inclination level
      increased by 1% every third minute, starting on 0% up to 3%. The velocity was
      kept constant at 0.97 m.s-1. Variables measured included oxygen uptake, minute
      ventilation, respiratory exchange ratio, heart rate, and stroke frequency.
      Analysis for repeated measures was conducted on the main factors slope and MA and
      their interaction. Additional analysis include a multiple regression analysis.
      All statistics were conducted with a p < 0.05 level of significance. MA had a
      significant effect (p < 0.05) on oxygen uptake, energy cost, mechanical
      efficiency, and stroke frequency. These results suggest that the implementation
      of a range of MAs on a lever-propelled wheelchair may accommodate different
      external conditions (slope, climatic, surface conditions, sports, and
      recreational conditions) and different user groups more readily. This may improve
      the social radius of action and freedom of mobility of individuals confined to
      wheelchairs.

PMID- 9239622
TI  - Biomechanical properties of human tibias in long-term spinal cord injury.
AB  - Long-term spinal cord injury (SCI) profoundly alters skeletal structure and
      function. In this study, the biomechanical properties of tibias from persons with
      SCI and from individuals closely matched in age and size but without SCI were
      quantified at both the structural and material levels. Nondestructive torsion
      tests were performed to determine apparent shear moduli for the tibia. The
      cortical thicknesses and polar moment of inertia were determined numerically.
      Four-point bending tests were performed to determine flexural modulus of
      elasticity on cortical bone specimens of the tibia. The apparent shear moduli of
      the SCI tibias were found to be lower than the non-SCI tibias (p < 0.05). The
      cortical thicknesses of the SCI tibias were significantly thinner than the
      control tibias (p < 0.05), while the polar moment of inertia showed no
      significant differences between control and SCI tibial cross sections (p > 0.05).
      The flexural modulus of elasticity of the cortical bone specimens were lower in
      the SCI tibias than the controls (p < 0.05). These differences suggest that
      tibias may undergo micro-structural changes as well as structural adaptation
      following SCI, which alter their mechanical properties.

PMID- 9239623
TI  - Sweat analysis following pressure ischaemia in a group of debilitated subjects.
AB  - This article examines the application of a simple technique for the collection of
      sweat to the investigation of tissue metabolites in 11 debilitated subjects
      attending a rehabilitation unit. It is applicable to subjects with a range of
      clinical conditions. Sweat was collected at the sacrum with the subjects either
      seated in a wheelchair or lying in bed, which was representative of their usual
      daily routine. The tissues could be loaded during sweat collection by sacral
      support in either of these positions. Collections were made for about 10 hours
      and interface pressures were recorded on at least two occasions. After the
      prescribed period, the sweat pads were removed and a quantitative analysis of a
      range of metabolites was performed. Metabolite concentrations may reflect local
      tissue viability and responses to loading. In unloaded tissues the metabolite
      concentrations were similar to those observed in nondisabled subjects in an
      earlier study. During prolonged loading at relatively low levels of pressure,
      there was elevation in the levels of some metabolites; for example 39 and 28%
      increases for lactate and urea respectively. Successive measurements on an
      individual over a period of months showed variations, which were small compared
      to those observed in either groups of nondisabled or debilitated subjects. These
      observations suggest that the technique may be best applied in clinical practice
      to monitor sequential changes in individual subjects.

PMID- 9239624
TI  - Dysarthric speech: a comparison of computerized speech recognition and listener
      intelligibility.
AB  - The purpose of this study was to identify and compare the recognition of
      dysarthric speech by a computerized voice recognition (VR) system and non-hearing
      impaired adult listeners. Intelligibility "functions" were obtained for six
      dysarthric speakers who varied in severity and six age- and gender-matched
      controls. Speakers produced 70-item word lists over 5 sessions. VR using the IBM
      VoiceType and perceptual judgment scores were obtained and functions plotted by
      session. Data indicate that computerized recognition of both dysarthric and
      nonimpaired speech was characterized by initially steep increases in correct
      recognition with more gradual increases noted during the second through fifth
      sessions. Perceptual recognition by non-hearing-impaired adults indicates
      generally stable intelligibility scores over time. Severity of dysarthria did
      appear to influence recognition of target stimuli. Implications of these data to
      the application of computerized VR technology are presented.

PMID- 9239625
TI  - Monitoring healing of acute Charcot's arthropathy with infrared dermal
      thermometry.
AB  - The purpose of this study was to describe the use of skin temperature assessment
      in diabetics with acute Charcot's arthropathy to monitor resolution of
      inflammation longitudinally throughout the course of treatment and to predict
      development of neuropathic ulcers. Thirty-nine diabetic subjects presenting with
      acute Charcot's arthropathy received thermometric monitoring throughout their
      treatment course. Subjects were treated with a standard protocol involving total
      contact casting, removable cast walkers, and progression to therapeutic shoes.
      There was a steady decrease in temperatures during the casting regimen. After
      temperature gradients normalized, subjects were progressed to custom therapeutic
      shoe gear and insoles and were followed for a mean 22.6 +/- 7.1 months. Following
      quiescence, 8% returned during the follow-up period with a new-onset neuropathic
      ulceration. Temperature gradients during taken the visit prior to ulceration were
      significantly higher in this group than for the rest of the population. Elevated
      temperatures were strongly correlated with the location of arthropathy.
      Temperatures decreased in a predictable manner as acute arthropathy resolved.
      Additionally, increased temperature gradients may be predictive of future
      ulceration.

PMID- 9239626
TI  - The development and clinical evaluation of a standing biofeedback trainer.
AB  - A new standing biofeedback training device, which includes a height-adjustable
      work table, weight-bearing sensors, and a real-time visual and auditory feedback
      system, has been developed for postural training. Sixty persons with hemiplegia
      after acute stroke or traumatic brain injury were randomly divided into Group A
      (experimental) and Group B (control). After a training period of 4 weeks, the
      percentage of postural asymmetry in Group A and Group B was reduced from 17.2 +/-
      10.8% and 17.0 +/- 10.0% to 3.5 +/- 2.2% and 10.1 +/- 6.4 percent, respectively
      (p = 0.003). There was no significant difference between subjects with right or
      left hemiplegia. The results indicated that this device had a positive training
      effect on stance symmetry in hemiplegic subjects.

PMID- 9239627
TI  - What is your diagnosis? Ankylosis of the left temporomandibular joint.

PMID- 9239628
TI  - External skeletal fixation for stabilisation of comminuted humeral fractures in
      cats.
AB  - Thirteen feline humeral fractures were stabilized using external skeletal
      fixation alone or in combination with supplementary devices. Eleven of the 13
      fractures healed. Pins placed in the distal humerus should be angled to avoid the
      supracondylar foramen and radial nerve. An intramedullary pin in combination with
      external skeletal fixation is indicated for mildly comminuted reconstructable
      fractures. For severely comminuted humeral fractures, closed application of an
      external skeletal fixator may be preferable to open reduction and internal
      fixation to provide healing and is recommended as an alternative to amputation.

PMID- 9239629
TI  - Evaluation of somatostatin analogues for the detection and treatment of
      gastrinoma in a dog.
AB  - Gastrinomas in dogs are difficult to diagnose, localise and treat. In humans,
      somatostatin analogues have improved localisation and treatment of gastrinomas.
      The somatostatin analogues pentetreotide and octreotide were evaluated for the
      detection and treatment of gastrinoma in a dog. 111indium-pentetreotide
      scintigraphy revealed multiple areas of activity in the patient's mid-ventral
      abdomen which were consistent with masses in the pancreas and liver at
      laparotomy. Immunohistochemistry, electron microscopy and binding of 125I-[Tyr3]
      octreotide in vitro confirmed the lesion as a gastrinoma which expressed
      somatostatin receptors. Octreotide at doses of 2, 4 and 8 micrograms/kg caused
      transient decreases in circulating gastrin. Plasma somatostatin peaked at one
      hour after octreotide and was still detectable at four and six hours after
      administration of octreotide. Combination therapy with famotidine, omeprazole,
      sucralfate and increasing doses of octreotide allowed patient survival for 14
      months.

PMID- 9239630
TI  - Myelography in the dog with non-ionic contrast media at different iodine
      concentrations.
AB  - Image quality and side effects were evaluated retrospectively in a series of 183
      myelographic studies performed with two non-ionic contrast media (iohexol and
      iopamidol) at different concentrations. Side effects during and following the
      procedure were recorded. Image quality was assessed using an arbitrary scoring
      system and statistical analysis was performed with the cross-tabulation test (4 x
      2 table) by comparing two groups receiving contrast medium at higher and lower
      concentrations. No significant differences in side effects were observed between
      the two groups but the ratings for image quality were significantly higher in the
      group receiving contrast medium at the higher concentration than in the group
      receiving the lower concentration. The results suggest that a high concentration
      of non-ionic contrast media can safely be used in dogs and may improve image
      quality.

PMID- 9239631
TI  - Tibiotarsal fracture repair in a scarlet macaw using external skeletal fixation.
AB  - Surgical repair of a fractured tibiotarsus in a scarlet macaw (Ara macao) is
      described. The forces imposed on the fracture site are discussed and the unique
      features of avian bone emphasised. Advantages of external skeletal fixation and
      specific details of the frame construction are highlighted.

PMID- 9239632
TI  - Naturally occurring xanthine urolithiasis in a domestic shorthair cat.
AB  - A five-year-old neutered male domestic shorthair cat was presented after three
      episodes of urethral obstruction and anuria requiring relief urethral
      catheterisation. A double contrast cystogram revealed the presence of multiple
      small cystoliths which were radiolucent on plain radiographs. A perineal
      urethrostomy and a cystotomy were performed to relieve the urethral obstruction
      and to remove the cystoliths. Quantitative analysis revealed the cystoliths to be
      composed of 100 per cent xanthine. Clinical history suggested the xanthinuria to
      be naturally occurring. Unfortunately, the cat was killed in a road traffic
      accident two months after the surgical procedure, preventing further long-term
      assessment.

PMID- 9239633
TI  - Bilateral xanthine nephrolithiasis in a dog.
AB  - Xanthinuria is an uncommon metabolic disorder clinically manifested as
      urolithiasis. There are two forms of the disease, congenital and iatrogenic. The
      former was diagnosed in a four-year-old dachshund bitch. The patient was
      presented with signs of terminal chronic renal failure. Urine was
      bacteriologically sterile with massive amorphous crystalluria. Bilateral
      nephrolithiasis was diagnosed at necropsy. The kidneys were shrunken with marked
      atrophy of the renal cortex and medulla. Infrared spectrometry revealed that the
      stones comprised 100 per cent xanthine. Later, two of the patient's siblings were
      examined for urine xanthine content; both showed higher concentrations of
      xanthine than a control dog. The described case is compared with seven known
      published cases of congenital xanthinuria.

PMID- 9239634
TI  - Diagnosis of pulmonary thromboembolism in a cat using echocardiography and
      pulmonary scintigraphy.
AB  - A 10-year-old male cat was presented with sudden onset of respiratory
      difficulties. Clinical examination revealed an acute dyspnoea with cyanosis
      associated with a left systolic heart murmur. Standard thoracic radiographs
      excluded pulmonary oedema and showed very few pulmonary changes given the
      intensity of the respiratory compromise. Echocardiographic examination revealed
      hypertrophic cardiomyopathy and a thrombus in the right pulmonary artery.
      Pulmonary scintigraphy confirmed a pulmonary thromboembolism with
      hypovascularisation of the left cranial lobe and of the ventral segment of the
      right lobe. Conservative treatment was instituted using an antibiotic
      (doxycycline), anticoagulants (heparin, coumadine) and a calcium inhibitor
      (diltiazem). The cat was given absolute rest. The general condition of the animal
      improved.

PMID- 9239635
TI  - Low serum immunoglobulin concentrations in related Weimaraner dogs.
AB  - Chronic, recurrent disease involving the alimentary tract, joints, skin and
      peripheral lymph nodes, central nervous system and conjunctivae was recorded over
      a 229 day period in a young Weimaraner dog, first presented at 15 weeks of age.
      The dog had a left shift neutrophilia during periods of active disease and
      persistently subnormal levels of serum immunoglobulin G (IgG; 2.8 to 9.2 mg/ml)
      and IgA (< 0.1 to 0.26 mg/ml) in the absence of circulating immune complexes. One
      littermate died suddenly at 27 weeks of age and a second littermate had an
      episode of pyoderma. Both of these dogs had low serum IgG (3.5 to 7.2 mg/ml) and
      the second littermate also had reduced serum IgA (< 0.1 to 0.15 mg/ml). The dam
      of the litter and three other related dogs had reduced serum IgA (0.22 to 0.31
      mg/ml); circulating immune complexes were not recorded in any of the related
      dogs. This case is the first of putative immunodeficiency of Weimaraners in the
      UK. Inability to synthesise adequate concentrations of serum immunoglobulins
      should be considered a primary defect in this disorder.

PMID- 9239636
TI  - Cryptosporidiosis.

PMID- 9239637
TI  - Anatomy of the normal acromion investigated using MRI.
AB  - The shape of the acromion is strongly associated with impingement syndrome and
      with rotator cuff tears. It is notoriously difficult to image the acromion with
      conventional radiography. We have developed MRI techniques to depict the acromion
      in its longitudinal axis. Furthermore, we have measured the subacromial space in
      both external and internal rotation. In previous studies, three types of acromial
      shape have been described with the type III or hooked acromion being present in
      66% of cases with rotator cuff tears. We studied 31 normal shoulders in 29 people
      using MRI. Within this population aged 24-36 years, mean age 31 years, no type
      III acromions were found. Twenty-one were type I (67.7%) and 10 were type II
      (32.3%). In addition, we found no difference in subacromial height in external or
      internal rotation. Low rates of intra- and interobserver error were found. These
      results imply that the hooked acromion is not present in the normal population
      and is, therefore, likely to be an acquired abnormality.

PMID- 9239638
TI  - True carcinosarcoma of the colon. Case report.
AB  - A second case of true carcinosarcoma of the colon is reported. A 79-year-old
      women was diagnosed as having an obstructing tumour of the caecum and liver
      metastases in both lobes. Histological examination of operative specimen from a
      right hemicolectomy revealed malignant epithelial and mesenchymal components.
      Despite postoperative chemotherapy, the patient died of liver failure resulting
      from extensive metastatic growth.

PMID- 9239639
TI  - Identification and physiological relevance of an exponentially tapered tube model
      of canine descending aortic circulation.
AB  - The aim of this study was to evaluate the effect of incorporating aortic tapering
      in a tube model of descending aortic circulation. We described the descending
      aorta and its peripheral load by an exponentially tapered transmission tube
      terminating in a first-order, low-pass filter load. Under the assumption of
      adaptation between the transmission tube and the terminal load, the input
      impedance of this model was characterized by five free parameters, the
      characteristic impedance, Zce(0), at the tube entrance; the product, qde, between
      the tapering factor q and the tube length, de, the product ce(0)de, between the
      compliance, ce(0), at the tube entrance and the tube length; the time constant,
      tau ne, of the load and the peripheral resistance, Rp. We estimated these
      parameters making use of experimental pressure and flow measurements taken from
      the high descending aorta of three anaesthetized dogs. We contrasted the
      behaviour of this model with that of a competing model constituted by a uniform
      transmission tube also terminating in a first-order low-pass filter load. We
      compared the data fits and, with the aid of an extra measurement of pressure in
      the abdominal aorta, we tested the congruence between the estimates of the
      transmission tubes' parameters and the physical and geometrical properties of
      descending thoracic aorta. The tapered tube model showed a slightly better
      ability in fitting to experimental flow and reproducing input impedance data.
      However, the estimates of the transmission tube parameters failed to assess the
      physical properties of descending aorta. By contrast, the estimates of tube
      parameters provided by the uniform model allowed location of the junction between
      the tube and its terminal load in the abdominal aorta at level of major branches.
      These estimates were well correlated with the real system's properties. In
      conclusion, the complexity added to the uniform tube model by accounting for
      exponential aortic tapering gave rise only to a better curve fitting, but did not
      show any identifiable benefits regarding physiological interpretation of the
      physical properties of the descending aorta.

PMID- 9239640
TI  - Comparison of different methods for the determination of the true wave
      propagation coefficient, in rubber tubes and the canine thoracic aorta.
AB  - The results from studies of wave propagation in large arteries carried out over
      the last 25 years have shown that there is a good agreement among values of the
      imaginary part of the complex propagation coefficient, as expressed by pressure
      or flow-rate wave propagation velocity. However, there is considerable disparity
      among estimations of the degree of wave attenuation, the real part of the
      propagation coefficient. In order to determine whether this disparity is due to
      differences inherent in the various methods used to measure true wave propagation
      coefficients or whether it is caused by differences in experimental conditions,
      we have compared three techniques for determining true pulse wave propagation
      coefficients the three-point method, the occlusion method and a recently
      described iterative procedure. In addition, the results were compared to apparent
      propagation coefficients calculated without accounting for reflections.
      Measurements were carried out using each method in turn on a rubber tube of known
      transmission characteristics in which the magnitude of reflections was small. The
      iterative procedure and the three-point method were also compared under
      conditions of strong reflection. In the tube, the values of propagation velocity
      and attenuation coefficient determined by each method were similar. Although some
      discrepancies were noted, they did not amount to a systematic trend. The
      iterative procedure and the occlusion method were also used to analyse
      measurements on the thoracic aorta of three anaesthetized greyhounds. In the
      animal experiments, in spite of increased scatter, partly due to the variation
      between dogs, the two methods for determining true pulse-wave propagation yielded
      similar results. Since the differences between our estimates of propagation
      coefficients obtained by the methods tested are small with respect to those found
      when comparing the results from several reports in the literature, we conclude
      that any discrepancies between studies cannot be due to problems associated with
      the methods themselves but must have been caused by variations in experimental
      conditions or by other unknown artefacts.

PMID- 9239641
TI  - A mathematical model of circulation in the presence of the bidirectional
      cavopulmonary anastomosis in children with a univentricular heart.
AB  - The bidirectional cavopulmonary anastomosis is used as a staged procedure or a
      definitive palliation of univentricular hearts. It is often performed in the
      presence of an additional blood flow arising from the native pulmonary outflow
      tract. In this paper, the effects of the severity of the pulmonary outflow
      obstruction and the pulmonary arteriolar resistance are analysed with regard to
      the haemodynamics in the superior vena cava and the blood distribution into the
      lungs. A computer model has been developed, which can represent both the
      preoperative and the postoperative (systemic and pulmonary) circulations in a
      patient with a double-outlet univentricular heart. It is particularly detailed in
      the region of the large vessels and includes components that account for local
      three-dimensional effects due to the actual shape of the anastomosis. Results
      have indicated that the mean pressure in the superior vena cava increases from
      8.2 to 19.2 mmHg with pulmonary arteriolar resistance ranging from 0.8 to 7.9
      Woods units and pulmonary outflow obstruction ranging from 50 to 100%. The
      percentage flow distribution to the right lung has turned out to be heavily
      affected by the flow competition and has ranged from 43 to 50% of the total flow
      to the lungs in the systolic phase, and from 51 to 62% in the diastolic phase.
      The model allows routinely used clinical indices to be computed, as well as the
      evaluation of new indices, which is potentially helpful in the clinical
      assessment of postoperative haemodynamics (e.g. the right-to-left lung flow ratio
      and the superior vena cava-to-pulmonary flow ratio).

PMID- 9239642
TI  - Three-dimensional study of the effect of two leaflet opening angles on the time
      dependent flow through a bileaflet mechanical heart valve.
AB  - A three-dimensional (3-D), time-dependent computational fluid dynamics (CFD)
      model was used to investigate the effect of leaflet opening angle on the flow
      through a fully open bileaflet heart valve up to peak systole. A laminar flow
      model of a Newtonian fluid was used, and the peak systolic. Reynolds number was
      1500, based on the aortic radius and the average velocity at peak systole. This
      resulted in a Reynolds number of 5800, based on the aortic radius and the local
      maximum velocity. The flow fields through and downstream of the bileaflet valves
      were complex, with strong time-dependent 3-D vortices being found in planes
      parallel and perpendicular to the leaflets. The parametric study of the effect of
      leaflet opening angle showed that, as the leaflet opening angle increased from 78
      degrees to 85 degrees, the flow downstream of the valve leaflets became more
      centralized, and the wake downstream of the leaflet decreased in size. However,
      as the opening angle increased from 78 degrees to 85 degrees, the maximum shear
      rate and the maximum velocity increased, suggesting that the design of the
      central orifice geometry was also an important consideration.

PMID- 9239643
TI  - An investigation of the stress distribution generated in articular cartilage by
      crystal aggregates of varying material properties.
AB  - Several joint diseases are associated with the deposition of crystals within the
      articular cartilage. A variety of crystal aggregates have previously been
      identified throughout the thickness of the cartilage. A linear elastic finite
      element model representing instantaneous, or short-term, loading conditions has
      been developed of a large crystal aggregate surrounded by articular cartilage.
      The material properties of the aggregate and the cartilage were varied and the
      resultant shear stress and equivalent strain distribution in the surrounding
      cartilage studied in order to provide some indication of the relative potential
      of various types of crystal aggregate to cause damage to the articular cartilage.
      Results indicated that aggregates with a Young's modulus either much less, or
      much greater, than that of the surrounding cartilage generated the maximum shear
      stress and equivalent strain concentrations at the interface between the
      aggregate and the cartilage. Also, that highly compressible aggregates, with a
      very low Poisson's ratio, generated higher shear stress and equivalent strain
      concentrations in the surrounding cartilage than aggregates of a more
      incompressible nature. Under conditions of short-term loading these results
      suggest that crystal aggregates present within the cartilage layer will increase
      the shear stress and equivalent strain concentrations in the surrounding
      cartilage, and therefore have the potential to cause damage to the cartilage.

PMID- 9239644
TI  - Producing physiologically realistic individual muscle force estimations by
      imposing constraints when using optimization techniques.
AB  - Static optimization techniques have been used to estimate individual muscle
      forces in order to assess joint loads and muscle function. This study examined
      the validity of such techniques. Forces in the individual muscles, causing elbow
      flexion, were estimated using four different objective functions, minimizing the
      sum of the muscle stress either squared or cubed, and minimizing the sum of the
      relative muscle forces either squared or cubed. Constraints were placed on the
      maximum muscle forces based on physiological considerations. The resulting force
      estimates were compared with those from a validated muscle model that took
      account of the physiological properties of the muscles. The objective functions
      produced physiologically unrealistic muscle force estimations, unless the maximum
      muscle forces were constrained. By imposing constraints, individual muscle force
      predictions were restricted to those that were within physiologically realistic
      bounds. Using this procedure for sub-maximal activity resulted in some muscle
      activity being equal to the constraint, which, whilst possible, is still
      unrealistic. Therefore, by imposing constraints, the muscle forces can be kept
      within physiological boundaries, but the inferred recruitment is not necessarily
      the solution that the 'body' selects, but reflects a set of muscle forces that
      meet the solution to the optimization problem.

PMID- 9239646
TI  - A high-speed gated baseline restorer and its implementation in a blood cell
      volume analyser.
AB  - Accurate measurement of the height of individual pulses in a signal that is a.c.
      coupled is dependent upon correcting a changing baseline to a constant value. A
      new fast baseline restorer, using internally triggered gated feedback with gain,
      has been designed and a version optimized for Gaussian-shaped pulses. Performance
      is dependent on the magnitudes of both the forward and the feedback gains. The
      design presented can achieve a 0.5% accuracy in pulse height for a minimum pulse
      width of 2.5 microseconds or for 5 microseconds overlapping pulses as long as the
      overlap is less than 50%. Typical applications for the baseline restorer include
      blood cell volume measurement systems, scintillation counters and radiation
      spectroscopy.

PMID- 9239645
TI  - Thermographic strain analysis of the proximal canine femur.
AB  - Thermographic strain analysis (TSA) was used to measure the surface strain
      distribution of cyclically loaded canine femora. Eleven canine femora were
      cyclically loaded at 20 Hz in compression at 600 N (+/-200 N). After calibration
      with measured local strain data, it was possible to quantify the full field
      patterns measured from the proximal, anterior and medial cortex. The average of
      each TSA signal normalized by the coincident strain data (0.996) was very near to
      1.0 (p = 0.999). The thermographical scans iterate the maximum compressive
      strains carried by the femur within the region just distal to the femoral neck.
      Further understanding of the strain distribution in this region is critical in
      the design of components that attempt to mimic anatomical load transfer after
      total hip arthroplasty. TSA appears to offer a promising technology as a full
      field experimental strain analysis method for use with biomechanical issues.

PMID- 9239647
TI  - Clinical assessment of the low-cost VariCom isokinetic knee exerciser.
AB  - A low-cost isokinetic knee exerciser, known as the VariCom and developed with the
      emphasis on fulfilling the rehabilitation needs of developing countries, was
      subjected to a clinical evaluation. The evaluation was motivated by successful
      laboratory assessment of the exerciser as well as encouraging qualitative data
      acquired recently from a developing world hospital. The principal aim of this
      study was to demonstrate that the exerciser, employing a simple shock-absorber
      and lever mechanism, was capable of fulfilling the major criteria required from
      isokinetic equipment. Amongst the most important of these were attainment of a
      'spectrum of velocities', patient safety, reliability, ease-of-use, patient
      comfort and estimation of the torque generated by the patient's knee-joint. It
      was ultimately demonstrated that the combination of design simplicity, durability
      and functionality renders the VariCom knee-exerciser technologically appropriate
      for use in developing countries. More generally, the success of the exerciser,
      combined with its low manufacturing cost, renders it a viable alternative to
      traditional up-market equipment.

PMID- 9239648
TI  - A comparison of ECG cancellation techniques applied to the surface recording of
      somatosensory evoked potentials.
AB  - The use of somatosensory evoked potentials (SEPs) for determining spinal cord
      integrity in a clinical setting is well known. The poor signal-to-noise (SNR)
      ratio of such measurements has led to ensemble averaging being employed to
      extract the signal from the background noise. Over the thoracic region, the poor
      SNR is largely the result of interference generated by the cardiac musculature.
      Therefore, any reduction in the level of this cardiac interference will greatly
      improve the performance of any SEP monitoring system. Three methods were
      investigated as techniques to reduce the cardiac interference in SEP
      measurements. These were clipping, gating and adaptive noise cancellation (ANC).
      It was found that, although clipping and gating performed as well as, if not
      better than, ANC, these techniques were both very sensitive to the setting of a
      threshold level. The linear ANC scheme employed circumvented the problem
      associated with a threshold level, and with an order of 50, SNR improvement
      figures of approximately sixfold were achievable over the entire thoracic region.

PMID- 9239649
TI  - A data-logging system to monitor bone fracture movement continuously.
AB  - A compact system is presented, which can continuously monitor the occurrence of
      fracture site movement in patients with tibial shaft fractures treated with an
      Orthofix external fixator allowing limited axial movement. The system comprises a
      microswitch and data logger board, which are both attached to the fixator. Each
      time the switch is closed by the movement of the fixator, the data logger records
      it as an event. The number of events per half hour is stored to the board's
      memory. The data logger can record the frequency of movement for at least a four
      week period, at which time, the data can be transferred to a computer via a
      serial link. The system has been proven in a limited patient trial. The results
      highlight the variation in patient mobility. The significance of continuously
      monitoring the fracture site movement during the healing period is discussed.

PMID- 9239650
TI  - Detection of cardiac late potentials in nonstationary noise.
AB  - An 'instantaneous' optimal filter is presented for improving the signal-to-noise
      ratio in averaged electrocardiograms (ECGs). The filter design is based on a
      simple model that accounts for correlation across the ensemble of beats but
      ignores correlation in time. Another property of the model is that the noise
      level is allowed to change from beat to beat. Simulation results indicate that an
      improved performance is achieved by the new filter when compared to a filter with
      a similar structure but designed for processing beats with a constant noise
      level. Several ECG examples are included to demonstrate the performance of the
      filter for detecting late potentials.

PMID- 9239651
TI  - Ag/AgCl/Cl- coated silver-stripe reference electrode.
AB  - This paper introduces a new type of miniaturized coated silver-stripe reference
      electrode without internal solution for single use and intends to give in detail
      the method used to prepare a Ag/AgCl/Cl- miniaturized coated silver-stripe
      reference electrode of a second kind which acts as a half-cell of a sensor system
      measuring Ca2+ ion activity in human blood as well as the difficulties
      encountered. The technique described is a cost-effective and time saving method
      for biomedical measurement.

PMID- 9239652
TI  - Retrovirus-mediated gene therapy to fetal lung.

PMID- 9239653
TI  - In-utero gene transfer--an approach to the treatment of inherited lung diseases.

PMID- 9239654
TI  - The window of opportunity for fetal gene therapy.

PMID- 9239655
TI  - Potential molecular mechanisms for the contraceptive control of implantation.

PMID- 9239656
TI  - Chromosome aberrations in human spermatozoa treated with Ca2+ ionophore A23187.
AB  - Incorporation of A23187 ionophore into the human-hamster fertilization system
      clearly improves the ability of human spermatozoa to penetrate zona-free hamster
      oocytes. Thus, an increasing number of laboratories working in human sperm
      cytogenetics have substituted classical incubation with Biggers-Whitten
      Whittingham (BWW) medium plus human serum albumin (HSA) by pretreatment of
      spermatozoa with calcium ionophore A23187 which directly induces the acrosome
      reaction in spermatozoa. However, there have been no formal studies on the
      effects of this ionophore pretreatment. To determine whether calcium ionophore
      could affect the cytogenetic characteristics of human spermatozoa we compared
      A23187-treated spermatozoa with controls (only incubated with BWW + HSA) by
      analysing a total of 447 sperm chromosome complements from two normal donors. Our
      results show that there are no statistical differences in the frequency and the
      types of human sperm chromosomal abnormalities between the two methods of sperm
      treatment. Thus, ionophore A23187 seems not to affect the cytogenetic
      characteristics of human spermatozoa, and the results of laboratories using
      either sperm capacitation in BWW + HSA or acrosome reaction by calcium ionophore
      can be compared.

PMID- 9239657
TI  - Analysis of the sex chromosomal equipment in spermatozoa of a 47,XYY male using
      two-colour fluorescence in-situ hybridization.
AB  - The sex chromosomes in spermatozoa of a 47,XYY fertile male were analysed
      simultaneously by dual fluorescence in-situ hybridization (FISH), with two probes
      (pHY2.1 and pXBR). Of the 100000 cells analysed, 95179 spermatozoa (95.18%)
      exhibited one or more hybridization signals. Of the hybridized nuclei, 85.37%
      showed a normal sex chromosome constitution (37.37% X-bearing cells and 48.00% Y
      bearing cells), with an X:Y ratio of 0.78:1. A total of 14.63% of the hybridized
      nuclei exhibited sex chromosome aneuploidy with a majority of XY- and YY-bearing
      spermatozoa (9.37 and 4.65% respectively). Even if the majority of spermatozoa
      have chromosomal haploidy, a large proportion of them exhibits numerical errors
      for the sex chromosomes. These observations raise questions about the commonly
      admitted notions concerning the absence of chromosomal risk for XYY male
      offspring.

PMID- 9239658
TI  - Isolation of human uteroglobin from blood filtrate.
AB  - The purpose of this study was to assess the possibility of isolating biologically
      active peptides from human blood using large volumes of blood filtrate, which are
      available from patients undergoing extracorporeal ultrafiltration because of
      renal insufficiency. This filtrate was submitted to six chromatographic
      separation steps, yielding one purified peptide which was completely analysed in
      its primary structure. It was found to be strikingly similar to proteins,
      described initially as rabbit uteroglobin (or blastokinin) and, more recently,
      from human bronchial lavage as the '10 kDa Clare cell protein', as well as from
      human urine as 'protein-1'. The natural molecule contains two chains of identical
      amino acid sequences of 70 residues which are arranged as an antiparallel dimer
      due to the disulphide bonds between two cysteines at positions 3 and 69. Mass
      analysis of the molecular forms yielded molecular weights from 15827 Da (non
      oxidized form) to 15859 Da (bi-oxidized form). We conclude that this peptide
      isolated from the filtrate represents the human uteroglobin, and we demonstrate
      for the first time that this peptide may be involved as a humoral factor in
      reproductive or other physiological functions.

PMID- 9239659
TI  - Detection of mRNA transcripts of beta 1 integrins in ejaculated human spermatozoa
      by nested reverse transcription-polymerase chain reaction.
AB  - Matrix proteins (e.g. fibronectin, laminin and vitronectin) and their receptors,
      especially beta 1 integrins, may play a role in sperm-oocyte interactions. These
      proteins are well described on spermatogenic cells but especially in ejaculated
      spermatozoa, the presence of mRNA as a necessity for their synthesis is not
      clear. Therefore the mRNA synthesis of the beta 1, alpha 3, alpha 4, alpha 5 and
      alpha 6 chains (fibronectin and laminin receptors) of the beta 1 integrins was
      investigated by nested reverse transcription-polymerase chain reaction (RT-PCR)
      in spermatozoa of human semen samples (n = 18) which showed normal classical
      semen parameters after swim-up preparation. After the second amplification, we
      obtained specific signals for mRNA transcripts of the beta 1, alpha 3, alpha 4
      and alpha 6 chains in 17 of 18 semen samples investigated. All control PCRs were
      negative for somatic cell transcripts and contamination by somatic cells was
      excluded. These results demonstrate for the first time that human ejaculated
      spermatozoa contain the mRNA transcripts of beta 1 integrins and support the role
      of these proteins in adhesive mechanisms in the fertilization process.

PMID- 9239660
TI  - Temporal expression of platelet-derived growth factor (PDGF)-A and its receptor
      in human preimplantation embryos.
AB  - In order to improve assisted fertilization in humans it is important to elucidate
      the mechanisms of control of growth and development in the early pre-embryo.
      Increasing evidence shows that growth factors are of importance for such control
      mechanisms. As platelet-derived growth factor (PDGF) has been shown to enhance
      growth in a number of tissues, it may also be important in human pre-embryo
      development. PDGF acts as a dimer (AA, BB or AB) through its receptors: alpha
      alpha, beta beta and alpha beta. In order to study the role of PDGF and its
      receptors, we have used reverse transcription-polymerase chain reaction (RT-PCR)
      to examine the presence of transcripts in human pre-embryos that were surplus
      from the in-vitro fertilization treatment of infertile couples. Transcripts for
      PDGF A were present in the oocyte, 8-cell, morula and blastocyst stages but not
      in the 4-cell stage. Transcripts for PDGF B were not detected at any stage. PDGF
      receptor (PDGFR)-alpha transcripts were found in the 4-cell, 8-cell and
      blastocyst stages but not in the oocyte or morula stages. Transcripts for PDGFR
      beta were detected from the 8-cell, morula and blastocyst stages but not in the
      oocyte or 4-cell stages. These results show that mRNA synthesis of both PDGF A
      and the two receptor subunits alpha and beta takes place from the 8-cell stage
      onwards, suggesting an autostimulatory pathway as a possible mechanism for growth
      factors during pre-embryo development.

PMID- 9239661
TI  - Role for glycoconjugates in cellular communication in the human reproductive
      system.

PMID- 9239662
TI  - Blastocyst-endometrial interaction: an appraisal of some old and new ideas.
AB  - The nature of the early interaction between blastocyst and endometrial epithelium
      is known to be highly specific within individual species. Despite this unique
      initial interaction, the trophoblast promptly establishes a common theme as
      invasive cells penetrate the endometrium and colonize its local blood vessels. In
      all animals with this type of implantation the blastocyst plays a more active
      role than the endometrial epithelium. The aggressive behaviour of the blastocyst
      may be induced by signals from the endometrium which has been primed with
      preimplantation ovarian steroids. Activation of the blastocyst may reflect
      triggering of synchronized paracrine loops, activated during the implantation
      window. Endometrial cytokines and eicosanoids are probably the primary signals
      that drive the interlinking paracrine loops and are essential for
      decidualization, trophoblast growth and invasion. Since the dominant feature of
      early implantation is rapid trophoblast migration, particularly in primates, the
      degree to which the blastocyst attaches to the apical surface of the luminal
      endometrial epithelium during implantation is uncertain. The thickness of the
      glycocalyx on the uterine luminal epithelium during the peri-implantation period
      varies considerably between species. Its role in blastocyst attachment, if any,
      and in trophoblast cell locomotion, requires further study. The molecular
      properties and functions of the uterine epithelial plasma membrane, and those of
      the interacting trophoblast at the site of implantation, have been largely
      neglected and require further extensive study.

PMID- 9239663
TI  - Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial
      epithelium.
AB  - Several adhesion molecules have been shown to occur at the surface of endometrial
      cells. One of these is the integrin alpha v subunit which associates with various
      beta chains including beta 5. We demonstrate the presence of integrin beta 5
      polypeptide in human endometrial epithelial cells throughout the menstrual cycle
      using immunocytochemistry with monospecific antibodies, and at the mRNA level by
      thermal amplification from endometrial cDNA. Integrin beta 5 is also found in a
      population of bone marrow-derived cells. A notable feature of the distribution of
      the beta 5 subunit in the glandular and luminal epithelium is its apical
      localization, which may suggest an involvement in implantation. However, no
      evidence was found for regulated expression of epithelial beta 5. In mouse, the
      beta 5 subunit is found at both the apical and basal surface of epithelial cells
      and expression is essentially oestrous cycle-independent. Comparisons are made in
      both species with the distribution of the alpha v and beta 3 subunits which also
      localize to the apical epithelium.

PMID- 9239664
TI  - Measurement of luteal and placental gonadotrophin-releasing hormone (GnRH)
      binding sites: role of inactivation of GnRH tracer.
AB  - The ability of radiolabelled gonadotrophin-releasing hormone (GnRH) and GnRH
      analogues to bind to homogenates and membranes of rat, rabbit and sheep pituitary
      and to luteal homogenates and membranes from a number of species was measured. In
      addition, inactivation of tracer during binding incubation was estimated by
      measurement of the ability of the unbound tracer fraction to bind to fresh GnRH
      receptor or anti-GnRH antibody. Following incubation of rat, sheep and rabbit
      pituitary gland with a radiolabelled GnRH agonist tracer, appreciable amounts of
      specific binding of GnRH agonist to fresh rat pituitary or human placental GnRH
      receptors could still be demonstrated. In contrast, no specific binding of [125I]
      labelled GnRH analogues were measured following incubation of the tracer with
      homogenates or membranes of bovine, sheep and porcine luteal tissue, nor with
      rabbit and rat placental homogenates. However, during incubation of GnRH tracers
      with these tissues, almost complete inactivation of GnRH tracers occurred. There
      was an inverse relationship between binding and inactivation of [125I]-labelled
      GnRH for a number of human corpora lutea. We conclude that degradation of GnRH
      tracers may prevent the measurement of specific GnRH binding sites in some
      tissues.

PMID- 9239665
TI  - Human granulosa cells in culture exhibit functional cyclic AMP-regulated gap
      junctions.
AB  - Numerous gap junctions exist between granulosa cells, between cumulus cells and
      between cumulus cells and the oocyte. They may play a role in the regulation of
      both follicular development and oocyte status. We used primary cultures of human
      granulosa cells to study the molecular nature and functionality of these gap
      junctions. As shown by a cinemicrographic technique, during the first 3 days of
      culture, cells flattened and extended in several directions by means of
      cytoplasmic extensions. An ultrastructural study showed the presence of both
      intercellular and annular gap junctions after 48 h of culture. As revealed by
      immunodetection analyses, connexin 43 was present. An analysis using a functional
      procedure, the gap fluorescence recovery after photobleaching (FRAP) method,
      indicated that: (i) diffusional communication existed among granulosa cells; (ii)
      the communication was delayed by treatment with 1-heptanol, a well-documented
      inhibitor of gap junction permeability; and (iii) permeability was up-regulated
      by incubation with 8-Br-cAMP, an analogue of cyclic AMP. The detection of
      connexin 43 and functional gap junctions in networks of cytoplasmic extensions
      indicated junction formation among cells during culture. In conclusion, our
      results show that human granulosa cells in culture exhibited functional gap
      junctions. Connexin 43 was present and the permeability of the gap junctions was
      up-regulated by cyclic AMP, an important modulator of human granulosa cell
      function.

PMID- 9239666
TI  - Cytokine induction of heat shock protein in human granulosa-luteal cells.
AB  - The infiltration of leukocytes is a characteristic feature of luteolysis in
      humans. Leukocytes are known to generate physiological inducers of cell stress
      such as cytokines which have been implicated as mediators of functional luteal
      regression. In cells exposed to stress, a response characterized by an increase
      in heat shock protein (HSP) synthesis occurs. Recently, the induction of HSP-70
      in rat luteal cells has been shown to inhibit luteinizing hormone (LH) and cAMP
      sensitive progesterone production, possibly by interfering with the translocation
      of cholesterol to the mitochondrial cytochrome P450scc. We therefore investigated
      whether HSP-70 is induced in human granulosa-luteal cells and its relationship to
      steroidogenesis. [35S]Methionine labelling showed an increase in a 70 kDa protein
      after heat treatment which was demonstrated to be HSP-70 by Western analysis
      using monoclonal antibodies against the constitutive and inducible forms of HSP
      70. Induction of HSP-70 in human granulosa-luteal cells was also seen with
      interferon (IFN) gamma (10 ng/ml), tumour necrosis factor (TNF)-alpha (100 ng/ml)
      and a combination of IFN gamma/TNF-alpha (10/50 ng/ml). Interleukin-1 beta (IL-1
      beta) (30 ng/ml) showed minimal induction of HSP-70 above control values. An
      increase in activated heat shock factor, which binds to the heat shock
      transcriptional control element, was detected after heat shock, IFN/TNF, and IFN
      treatment. Coincident with the induction of HSP-70 by heat shock was the
      inhibition of progesterone production compared with non-shocked granulosa-luteal
      cells. Heat shock inhibition of progesterone synthesis was partially reversed by
      the cell- and mitochondria-permeant cholesterol analogue, 22R-hydroxycholesterol.
      Cell viability was unaffected by heat treatment. White blood cell-depleted
      granulosa-luteal cell cultures treated with IFN demonstrated a significant
      reduction in progesterone production. Treatment with IFN/TNF, TNF, and IL-1 also
      decreased progesterone secretion, although statistical significance was not
      achieved. These findings provide evidence that a stress response occurs in human
      granulosa-luteal cells in response to heat and cytokines. The inhibition of
      gonadotrophin-sensitive steroidogenesis coincident with the induction of HSP-70
      synthesis by physiological agents which are present in the corpus luteum
      implicates HSP-70 as a potential mediator of luteolysis in the human.

PMID- 9239667
TI  - Granulocyte-macrophage colony-stimulating factor: presence in human follicular
      fluid, protein secretion and mRNA expression by ovarian cells.
AB  - In recent years it has become evident that a leukocyte-cytokine network
      contributes to the paracrine regulation of ovarian function. The objectives of
      this study were to examine the presence of a potent lympho-haemopoietic cytokine,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), in tissues and fluids
      from human ovaries. In a prospective study, follicular fluid and plasma were
      collected from naturally cycling women and women undergoing hyperstimulation for
      in-vitro fertilization (IVF). Granulosa-lutein cells were collected at the time
      of oocyte recovery for IVF and corpora lutea were collected at the time of
      hysterectomy for non-ovarian reasons. Culture supernatants from ovarian cell and
      tissue cultures were harvested on completion of a 48 h incubation. Immunoactive
      GM-CSF was measured by enzyme-linked immunosorbent assay, and was found to be
      present at statistically significantly higher levels in follicular fluid (8.9 +/-
      0.7 pg/ml) and plasma (11.3 +/- 0.8 pg/ml) of women undergoing hyperstimulation
      compared to follicular fluid (5.3 +/- 0.3 pg/ml) and plasma (7.1 +/- 0.5 pg/ml)
      from naturally cycling women. Immunoactive GM-CSF was also detected in culture
      supernatants of granulosa-lutein cells (47.6 pg/10(5) cells), early luteal phase
      corpora lutea (0.52 pg/microgram DNA) and mid-luteal phase corpora lutea (0.98
      pg/microgram DNA). Furthermore, transcripts for GM-CSF, and both the alpha and
      beta subunits of the GM-CSF receptor, were detected by reverse transcription
      polymerase chain reaction (RT-PCR) in granulosa-lutein cell culture preparations
      and corpora lutea collected during the early, mid- and late luteal phase of the
      menstrual cycle. These results show that GM-CSF is expressed and secreted by
      cells within the human ovary, and, together with the finding of expression of
      mRNA for GM-CSF receptor, suggest a role for GM-CSF in the local regulation of
      ovarian events.

PMID- 9239668
TI  - Studies on the relative in-vitro biological potency of the naturally-occurring
      isoforms of intrapituitary follicle stimulating hormone.
AB  - In the present study, we analysed and compared the relative in-vitro biological
      activity of the various intrapituitary human follicle stimulating hormone (FSH)
      isoforms employing two different bioassay systems. FSH was fractionated by
      chromatofocusing (pH range 7.10 to < 3.80) and the several isoforms isolated were
      quantified at multiple dose levels by three highly specific immunoassay systems:
      radioimmunoassay (RIA), enzyme-immunoassay (EIA) and immunoradiometric assay
      (IRMA), as well as by two in-vitro bioassays, one that measures the amount of
      oestrogen produced by rat granulosa cells in culture and the other that
      determines the amount of cAMP produced by a human fetal cell line (293)
      expressing the recombinant human FSH receptor. The relative in-vitro biological
      activity of each FSH isoform, expressed as the bioassay/ immunoassay (B/I)
      activity ratio (B/RIA, B/EIA and B/IRMA ratios) varied with its elution pH value.
      Regardless of the immunoassay or bioassay method employed, less acidic FSH
      isoforms exhibited higher B/I ratios than their more acidic counterparts [B/RIA,
      B/EIA and B/IRMA ratios for isoforms with elution pH values > 4.5 = 1.05 +/-
      0.13, 0.99 +/- 0.10 and 1.15 +/- 0.08 (rat oestrogen bioassay), and 2.75 +/-
      0.34, 2.20 +/- 0.25 and 2.96 +/- 0.35 (human cAMP production bioassay)
      respectively. Ratios for isoforms with pH values < 4.5 = 0.71 +/- 0.06, 0.47 +/-
      0.05 and 0.63 +/- 0.06 (rat oestrogen assay), and 1.80 +/- 0.26, 1.10 +/- 0.09
      and 1.44 +/- 0.13 (cAMP assay) respectively (P < 0.05 for isoforms with pH < 4.5
      compared with those isoforms with pH > 4.5)]. Furthermore, statistically
      significant direct relationships between the B/RIA, B/EIA and B/IRMA ratios and
      elution pH value of each isoform was identified by regression analysis [rat
      assay: r = 0.844, 0.800 and 0.780 (P < 0.01); human assay: r = 0.730, 0.845 and
      0.821 (P < 0.01), for their corresponding B/RIA, B/EIA and B/IRMA ratios
      respectively]. The finding of significant differences in relative in-vitro
      biological potency among the various intrapituitary FSH isoforms strongly
      suggests that the shifts towards the production and secretion of more basic or
      acidic FSH molecules occurring in certain specific physiological conditions (e.g.
      puberty and menstrual cycle), may represent an important mechanism through which
      the anterior pituitary regulates gonadal function.

PMID- 9239669
TI  - Glutamylated tubulin as a marker of microtubule heterogeneity in the human sperm
      flagellum.
AB  - Four site-directed monoclonal antibodies (mAbs) to tubulin: DM1A and DM1B general
      anti-alpha and anti-beta tubulin, 6-11B-1 anti-acetylated alpha tubulin and GT335
      anti-glutamylated alpha and beta tubulin were used to study the distribution of
      tubulin isoforms in the human sperm flagellum. Since indirect immunofluorescence
      (IIF) did not give reliable results, a quantitative study of the immunogold
      labelling of the flagellum was performed at five levels: the mid-piece, three
      successive regions of the principal piece and the terminal piece. A uniform
      labelling was observed with DM1A, DM1B and 6-11B-1 mAbs. In contrast, the
      labelling of glutamylated tubulin detected with GT335 mAb decreased from the
      middle piece to the terminal piece both for peripheral doublets and the central
      pair. The changes in labelling of peripheral doublets were related to the pattern
      of outer dense fibre (ODF) changes. Thus doublets 1-5-6, associated with the
      largest number of ODF, were the most heavily labelled. This predominant labelling
      corresponded to the plane of flagellar beating suggesting a functional
      heterogeneity of peripheral doublets.

PMID- 9239670
TI  - Recombinant human zona pellucida glycoprotein 3 induces calcium influx and
      acrosome reaction in human spermatozoa.
AB  - Recombinant human ZP3 (rhuZP3) generated by Chinese hamster ovary cells
      transfected with a plasmid containing human ZP3 cDNA was used to study the
      acrosome reaction (AR) and intracellular calcium fluxes in capacitated human
      spermatozoa. Conditioned medium containing rhuZP3 significantly induced the AR (P
      < or = 0.005) in 59.4 +/- 4.7% of spermatozoa (control = 8.5 +/- 3.1%) and caused
      complete acrosomal loss in a further 17.2 +/- 3.8% of cells (control = 3.7 +/-
      0.7%; mean +/- SEM, n = 5). Sperm motility was not affected and acrosomal
      exocytosis in response to rhuZP3 was also shown to be time-dependent. Basal
      concentrations of sperm intracellular calcium were measured (82 +/- 7 nM; mean +/
      SEM, n = 9). A transient increase in intracellular calcium (typically up to 400
      450 nM) occurred within 1 min of rhuZP3 addition and was followed by sustained
      lower values of calcium (200-400 nM). These responses were dependent on the
      amount of rhuZP3. This is the first report of zona protein-induced changes in
      intracellular calcium levels in human spermatozoa. The results support the
      premise that ZP3 is an agonist of the human sperm AR and that rhuZP3 generated in
      a eukaryotic cell is effective in this respect.

PMID- 9239671
TI  - The role of phosphocreatine kinase in the motility of human spermatozoa supported
      by different metabolic substrates.
AB  - In the spermatozoa of some species creatine kinase (CK: E.C. 2.7.3.2) is involved
      in shuttling energy, in the form of creatine phosphate, between the mid-piece
      mitochondria and flagellum. In this study, the effects of the CK inhibitor
      dinitrofluorobenzene (DNFB) on human sperm CK activity, motility and ATP
      concentrations were assessed with different energy substrates. There was a dose
      dependent inhibition of CK activity by DNFB but inhibition was incomplete and
      there was no effect on the percentage of flagellating cells, irrespective of
      substrate. However, when lactate alone supported the cells DNFB decreased
      velocities and increased amplitude of head displacement (fewer progressively
      motile forms were observed), whereas ATP concentrations in spermatozoa were
      unaltered. Demembranated sperm models could be reactivated by ADP plus creatine
      phosphate, but not to the extent caused by ATP, and were able to be inhibited by
      myokinase inhibitors. Increased velocities, linearity (LIN) and beat cross
      frequency (BCF) were demonstrated for spermatozoa incubated with lactate, in
      contrast to glucose as sole energy source, and higher velocities and BCF were
      generated in the presence of both substrates. This suggests that the production
      of ATP by glycolysis and respiration are independent and complementary. CK is not
      obligatory for sperm motility but supplements energy provision under certain
      conditions.

PMID- 9239672
TI  - Inhibition of sperm-zona binding by suramin, a potential 'lead' compound for
      design of new anti-fertility agents.
AB  - Progress in developing new contraceptive agents, particularly for the male, is
      extremely slow. Here, we report on a novel property of the anti-trypanosomal drug
      suramin: the ability to act at the sperm-egg interface and prevent fertilization.
      Suramin is a polysulphonated compound that inhibits binding of capacitated mouse
      spermatozoa to the zona pellucida in vitro with an IC50 of 12.4 microM. The drug
      is only effective at the time of fertilization and is not inhibitory if gametes
      are pre-treated separately. Autoradiographic localization of suramin binding
      sites on mouse, boar and human spermatozoa shows that they are intracellular,
      principally in the head region. The sperm protein recognized by suramin has been
      identified as proacrosin which is known to interact with sulphate groups on zona
      glycoproteins. Zona pellucida glycoproteins do not bind suramin, suggesting that
      the drug blocks the ability of proacrosin/acrosin, exposed during the acrosome
      reaction, to mediate the secondary binding phase of spermatozoa to the zona
      during fertilization. Structure-based design studies have the potential to
      generate safe suramin mimetics that would form the basis for a new generation of
      non-steroidal contraceptive agents.

PMID- 9239673
TI  - Identification of nitric oxide synthase in human and bovine oviduct.
AB  - Nitric oxide synthase (NOS) is responsible for the biological production of
      nitric oxide (NO) in several organs. NOS activity has also been localized in the
      reproductive tract, although direct evidence for its presence in the human or
      bovine oviduct is still lacking. In the present study, four different techniques
      were used to identify the presence of NOS activity in human (n = 11) and bovine
      (n = 9) oviduct: (i) conversion of [3H]-L-arginine to [3H]-L-citrulline; (ii)
      production of nitrite/nitrate (NO2/NO3; stable NO metabolites); (iii)
      identification of NADPH-diaphorase activity; and (iv) immunostaining with
      antiserum to endothelial NOS. Cytosolic extracts from human ampullary segments of
      the Fallopian tube, obtained from post-partum patients (n = 4), converted [3H]-L
      arginine to [3H]-L-citrulline (21.0 +/- 8.8 fmol/mg protein/min). This conversion
      rate was significantly (P < 0.05) reduced in the presence of either EDTA or N
      monomethyl-L-arginine monoacetate (L-NMMA), an inhibitor of NOS activity. When
      bovine (n = 3) ampullary segments were incubated for 36 h in Hanks' balanced salt
      solution, the concentration of NO2/NO3 in the medium was increased (P < 0.05) if
      segments were pretreated with lipopolysaccharide (LPS; an inducer of inducible
      NOS), but not after treatment with LPS + L-NMMA. Additionally, epithelial cells
      cultured from ampullary segments showed positive staining both for NADPH
      diaphorase activity and with antiserum to endothelial NOS. The results of the
      present study provide direct evidence for the presence of both the Ca(2+)
      dependent constitutive form of NOS, as well as the inducible form of NOS activity
      in human and bovine oviduct. Since the oviduct plays a key role in the
      reproductive process, it is possible that the two forms of NOS may be involved in
      the physiological regulation of oviduct function.

PMID- 9239674
TI  - A comparison of baseline and induced DNA damage in human spermatozoa from fertile
      and infertile men, using a modified comet assay.
AB  - Baseline DNA damage in spermatozoa from fertile and infertile men was compared
      using a modified alkali single cell gel electrophoresis (comet) assay. Semen from
      normozoospermic fertile, normozoospermic infertile and asthenozoospermic
      infertile (World Health Organization criteria, 1992) samples were studied. No
      significant difference was observed in levels of baseline damage between the
      three groups. A median value for baseline damage of approximately 20% (80% head
      DNA) was obtained in all samples. Irradiation with X-rays (5-30 Gy) produced no
      additional damage in fertile samples when median values were examined. However,
      irradiation with 30 Gy X-rays produced significant damage in both infertile
      groups. Hydrogen peroxide (40 microM) treatment induced significant damage in the
      asthenozoospermic group, whereas 100 microM H2O2 was required to cause
      significant damage in the normozoospermic fertile and infertile samples. Within
      the fertile population a subgroup in which percentage head DNA was greater than
      80% was observed in both treated and untreated specimens. This subgroup
      significantly decreased with treatment in both infertile groups. We conclude that
      the asthenozoospermic infertile group is more susceptible to damage than the
      normozoospermic infertile group, which in turn is more susceptible than the
      fertile group. The fertile group contains a resistant subpopulation of
      spermatozoa with relatively intact DNA.

PMID- 9239675
TI  - Expression of intercellular junctions during preimplantation development of the
      human embryo.
AB  - A total of 74 human embryos were stained with gap junction protein specific anti
      peptide antibodies an antibodies to the desmosomal protein desmoplakin to reveal
      the expression pattern of intercellular junctions during preimplantation
      development. Prior to implantation, the human embryo expresses predominantly
      connexin (Cx43)-containing gap junctions. Gap junctions were first detected in
      apposing cell membranes at the 4-cell stage and became increasingly organized as
      development proceeded. In normal blastocysts, trophectoderm (TE) cells were
      linked by dense arrays of gap junctions while inner cell mass (ICM) cells were
      linked by small, punctate gap junctions. Gap junctions containing Cx32 or Cx26
      were observed occasionally in the TE of late blastocysts. Desmosomes appeared
      between outer cells prior to cavitation and were retained in the TE, but not in
      the ICM. Levels of gap junction protein expression were variable in
      morphologically normal embryos at the same stage, suggesting that a normal
      appearance may not be a reliable indicator of future viability. Morphologically
      normal embryos often possessed multinucleate, apoptotic and decompacting cells.
      They could show either extensive, disorganized over-expression or reduced
      expression of gap junction protein. The results fit the view that only embryos
      destined to survive display an organized pattern of intercellular junctions.

PMID- 9239676
TI  - Fetal somatic gene therapy.
AB  - Fetal somatic gene therapy is emerging as a new experimental approach, in
      particular to prevent irreversible perinatal disease manifestation for many
      inherited conditions. Early therapeutic gene application may also allow targeting
      of still expanding stem cell populations of organ or cell systems inaccessible
      later in life and help to avoid immune sensitization against the therapeutic
      vector system or transgene protein product. The progress in development of
      ultrasound scanning and embryofetoscopy over the last decade has made minimally
      invasive administration of therapeutic gene transfer vectors to the fetus in
      utero possible in principle. We review here the different considerations in
      choosing candidate diseases, the possible routes of administration and times in
      fetal development for application of a therapeutic gene and discuss the benefits
      and problems of present vector systems in this context. Given the many unknown
      aspects of fetal gene transfer, it is essential to extensively investigate this
      new approach to gene therapy in animal models for specific diseases, to improve
      on the technology of delivery and to assess efficacy of expression as well as the
      possible side effects before application to humans can be considered.

PMID- 9239677
TI  - More in-vitro bioactive, shorter-lived human chorionic gonadotrophin charge
      isoforms increase at the end of the first and during the third trimesters of
      gestation.
AB  - In the present study we analysed the dynamics of serum human chorionic
      gonadotrophin (HCG) charge isoform distribution throughout normal gestation and
      characterized some of the biological features of the several HCG glycoforms
      present in the circulation of pregnant women. Blood samples were obtained from
      normal pregnant women at 10-11, 12-15, 23-26 and 35-38 weeks of gestation. The
      sera were fractionated by preparative chromatofocusing and the separated HCG
      isoforms were identified and quantified by radioimmunoassay. The in-vitro
      biological activity and the plasma half-life of the several circulating HCG
      isoforms were determined by conventional methods. HCG isoforms became less acidic
      as pregnancy advanced. In samples taken at 10-11 weeks of gestation, the most
      acidic HCG molecules (pH < 3.7) comprised > 80% of total HCG recovered after
      chromatofocusing; this proportion decreased to 58, 60 and 47% in samples taken
      from weeks 12.1 to 38.4 of gestation. Meanwhile, the relative proportion of less
      acidic isoforms recovered within pH values 6.49-4.50 increased at the end of the
      first trimester (12-15 weeks), remained constant until weeks 23-26 and then
      increased further by the end of the third trimester. Less acidic isoforms had
      higher in-vitro biological potency per immunological unit than the more acidic
      analogues. Regardless of the trimester of pregnancy, the plasma half-life of the
      highly acidic (elution pH < 3.7) isoforms varied from 84.4 to 150 min (116.3 +/-
      23.0; mean +/- SD), whereas the corresponding half-life of mid-acidic (pH 4.25
      5.31) and low-acidic (pH 5.74-6.50) HCG isoforms ranged from 31.0 to 115.3 (75.5
      +/- 20.6) and 15.3 to 58.3 (41.2 +/- 14.3) min respectively (P < 0.01, highly
      acidic versus mid- and low-acidic analogues and mid-acidic versus least acidic
      isoforms). The overall data indicate that the human trophoblast is able to
      regulate the exact intensity, biochemical composition and duration of the
      gonadotrophic stimulus secreted during the course of normal gestation. They also
      suggest that the decrease and maintenance of low serum HCG concentrations during
      the second and third trimesters of gestation may be partially caused by changes
      in the carbohydrate structure of the HCG molecule.

PMID- 9239678
TI  - Lectins binding on human sperm surface increase membrane permeability and
      stimulate acrosomal exocytosis.
AB  - Cross-linked complexes formed between certain lectins and their specific
      multivalent carbohydrates and glycoconjugates on the sperm surface were studied
      for their ability to modify sperm membrane permeability and to induce the
      acrosome reaction. Wheat germ agglutinin (WGA), concanavalin A (Con A) and peanut
      agglutinin (PNA) increased the proportions of human spermatozoa permeable to the
      impermeable propidium iodide (31.9 compared with 13.8%, 38.4 compared with 18.4%
      and 72.7 compared with 18.9% respectively). Removal of sperm surface sialic acid
      by neuraminidase treatment was a prerequisite for Con A and PNA binding to the
      sperm surface. The percentage of permeable and acrosome-reacted spermatozoa was
      not affected by sperm treatment with 500 mIU/ml Arthrobacter ureafaciens
      neuraminidase. WGA did not induce the acrosome reaction, whereas PNA induced the
      acrosome reaction regardless of the sperm capacitation status, allowing the
      proportion of acrosome-reacted spermatozoa to reach 27.7% of capacitated
      spermatozoa. However, the ability of Con A to induce the acrosome reaction was
      limited to uncapacitated spermatozoa. To test the physiological relevance of this
      study, uncapacitated human spermatozoa were incubated with human zonae pellucidae
      and the permeability of spermatozoa bound to the zona surface was analysed
      according to the time post-insemination. Two-thirds of spermatozoa bound to zona
      pellucida became permeable to propidium iodide in the first 30 min post
      insemination and almost all bound spermatozoa became permeable to the impermeable
      dye after 60 min. Our results show that molecular interactions between human zona
      pellucida and sperm surface increase the permeability of sperm membranes; the
      cross-linked complexes formed by PNA lectin and its specific multivalent
      carbohydrates and glycoconjugates on the sperm surface were also able to increase
      sperm membrane permeability and to induce the acrosome reaction. These results
      suggest a role for the saccharide moieties of sperm surface glycoconjugates in
      the induction of the acrosome reaction.

PMID- 9239679
TI  - Type 1 angiotensin II receptors in human endometrium.
AB  - From evidence based on the use of specific receptor subtype antagonists, it has
      generally been assumed that human uterine tissue contains only type 2 (AT2)
      angiotensin II (AII) receptor subtype. Using a monoclonal antibody, 6313/G2,
      directed against a specific sequence in the extracellular domain of the type 1
      AII receptor (AT1), in immunocytochemical studies, we show here that AT1 receptor
      is expressed in human endometrium. In particular, positive staining was seen in
      the endometrial glandular epithelium, and in the vascular endothelium, while the
      myometrium and endometrial stroma were negative. The most intense staining was
      observed during the late proliferative phase and less in the luteal phase. The
      ligand binding assay, using [125I]-angiotensin II, revealed high concentrations
      of AII receptors both in the endometrium and in the myometrium. Competition
      studies using losartan (AT1 specific) and CGP42112B (AT2 specific) showed that
      both AT1 and AT2 receptor subtypes were present in the endometrium, though only
      the AT2 receptor subtype was detected in the myometrium. Immunoblotting confirmed
      that the antibody 6313/G2 detected a single protein with a molecular weight of
      approximately 60 kDa. These data clearly demonstrate the presence of endometrial
      AT1 receptors whose expression appears to be under hormonal control.

PMID- 9239680
TI  - Rapid chromosomal analysis of germ-line cells by FISH: an investigation of an
      infertile male with large-headed spermatozoa.
AB  - A rapid fluorescence in-situ hybridization (FISH) technique was used for direct
      chromosomal analysis on germ cells from an infertile male with large-headed
      spermatozoa. The interphase chromosomes were fluorescently-labelled using an
      extremely bright cyanine dye during a 5-15 min FISH procedure. Germ cells were
      analysed using a battery of chromosome-specific DNA probes in several consecutive
      rapid FISH experiments. It was found that the majority of large-headed
      spermatozoa contained a diploid chromosome number probably due to errors in
      meiosis I or II divisions, whereas the majority of spermatozoa with normal sized
      heads are haploid and may be utilized for selective in-vitro fertilization
      procedures. Rapid FISH may be useful for the detection of major chromosomal
      aneuploidies in germ cells as an alternative technique to standard or multicolour
      FISH, and may find an additional application for the chromosomal analysis of
      human preimplantation embryos.

PMID- 9239681
TI  - Mutations in the cystic fibrosis gene in men with congenital bilateral absence of
      the vas deferens.
AB  - This paper reviews the relationship between mutations in the cystic fibrosis (CF)
      gene (CFTR mutations) and congenital bilateral absence of the vas deferens
      (CBAVD). Two CFTR mutations were identified in 14.5% of the 449 man with CBAVD
      thus far reported in the literature while one CFTR mutation was found in another
      48.1%. CBAVD appears to be a heterogeneous genetic condition, many cases being
      mild forms of cystic fibrosis, others having no relationship with CF. The 5T
      allele has also been found in 46% of men with CBAVD, but is not associated by the
      'classical' picture of cystic fibrosis. The role of the CFTR gene presumably
      extends beyond a normal development of the vas deferens, possibly playing a role
      in spermatogenesis. The detection of CFTR mutations in CBAVD had considerable
      implications in genetic counselling. Couples requesting microsurgical epididymal
      sperm aspiration/in-vitro fertilization and those in which the man has CF should
      be offered CFTR mutations screening if CBAVD is the cause of the male
      infertility.

PMID- 9239682
TI  - Purification and characterization of placental heparanase and its expression by
      cultured cytotrophoblasts.
AB  - The role of different extracellular matrix (ECM)-degrading enzymes in the normal
      functioning of the placenta is well documented. Heparan sulphate proteoglycan
      (HSPG) is an integral constituent of the placental and decidual ECM. Because this
      proteoglycan specifically interacts with various macromolecules in the ECM, its
      degradation may disassemble the matrix. Hence, in the case of the placenta, this
      may facilitate normal placentation and trophoblast invasion. Crude placental
      specimens were collected from first and third trimester placentas. Heparanase
      (endo-beta-glucuronidase) was isolated and purified by ammonium sulphate
      precipitation followed by sequential chromatographies on carboxymethyl-, heparin-
      and ConA-Sepharose columns. The placental enzyme was further characterized for
      its molecular weight and specific inhibition by heparin, and was shown to
      resemble heparanase expressed by highly metastatic tumor cells and activated
      cells of the immune system. In order to locate the source of heparanase activity
      in the placenta, primary cytotrophoblast cultures were established. Intact cells,
      as well as conditioned medium and cell lysates, were analysed for heparanase
      activity using metabolically sulphate-labelled ECM as a natural substrate.
      Heparanase was highly active in lysates of cytotrophoblasts. This activity was
      also expressed by intact cytotrophoblasts seeded on ECM, but no activity could be
      detected in the culture medium. Incubation of the cytotrophoblasts in contact
      with ECM resulted in release of ECM-bound basic fibroblast growth factor (bFGF).
      We propose that the cytotrophoblastic heparanase facilitates placentation,
      through cytotrophoblast extravasation and localized neovascularization.

PMID- 9239683
TI  - Hyaluronan, CD44 and its variant exons in human trophoblast invasion and
      placental angiogenesis.
AB  - Both hyaluronan and one of its receptors, CD44, can be demonstrated in the early
      human conceptus and in placental stroma. The variants of CD44 resulting from
      variable exon splicing are found in metastasizing human malignancies and are also
      involved in hyaluronan uptake and degradation. The resulting hyaluronan fragments
      are known to be highly angiogenic. We postulated that the self-limited process of
      trophoblast invasion of the uterine decidua results in part from the strategy of
      alternative splicing of CD44, similar to that used by invasive cancer cells in
      the course of metastatic spread and possibly angiogenesis. Monoclonal antibodies
      specific for CD44s and for an exon expressed during metastatic tumour
      progression, CD44v7, were used to examine this hypothesis. In this study we found
      human trophoblasts, for the first time, to express CD44. Intermediate
      trophoblasts of first and second trimester exhibited the standard form of CD44
      while extravillous trophoblasts, which are responsible for the invading
      characteristics of the placenta, were positive for the alternatively spliced
      form, the CD44v7-8. Moreover, in the case of placenta accreta there was a
      prominent membrane staining of the trophoblasts that were embedded in the fibrin
      layer over the myometrium. The highly metastatic choriocarcinoma cells also
      expressed CD44v7-8. We propose, therefore, that the invading trophoblasts utilize
      the alternatively splicing machinery. These cells retain their invasive
      capabilities through the permissive ECM by carrying the CD44v7-8 isoform, which
      binds weakly to hyaluronan and thus prevents it from being degraded by
      intracellular hyaluronidase.

PMID- 9239684
TI  - Expression of the cystic fibrosis (CF) and multidrug resistance (MDR1) genes
      during development and differentiation in the human placenta.
AB  - The aims of this study were to establish whether both the cystic fibrosis (CF)
      and multidrug resistance (MDR1) genes are expressed in the human placenta during
      development and differentiation. To study their pattern of expression during
      development, RNA was extracted from first, second and third trimester human
      placentas. To investigate differentiation, RNA was extracted from cytotrophoblast
      cells isolated from human term placentas and maintained in culture for 18, 66, 90
      and 114 h and from the undifferentiated choriocarcinoma cell line JAr. Using the
      reverse transcriptase-polymerase chain reaction (RT-PCR) with gene specific,
      intron spanning primers, a cDNA product of 1 kb, as expected for CF expression,
      was detectable following 35 cycles of PCR from all RNA samples except those from
      JAr; in the latter a product was only detected in one sample out of four separate
      passages and this was only just detectable after 40 cycles of PCR. RT-PCR using
      MDR1 specific primers resulted in a product from all samples at 0.34 kb as
      expected if this gene is expressed. These results demonstrate that both the CF
      and MDR1 genes are expressed in the human placenta at all stages of development
      and differentiation, although the expression of the CF, but not the MDR1, gene
      appears to be much weaker in the undifferentiated JAr cells in comparison with
      cytotrophoblast cells.

PMID- 9239685
TI  - Effects of protein kinase C activation and inhibition on sperm-, thimerosal-, and
      ryanodine-induced calcium responses of human oocytes.
AB  - Previous data have shown that protein kinase C (PKC) participates in the
      mechanism of sperm-induced calcium oscillations in mammalian oocytes, but the
      actual role of this enzyme in the oscillation mechanism is still unknown. In this
      study we show that drugs modulating PKC activity disturb the oscillations induced
      by spermatozoa, thimerosal and ryanodine, but in a different way for each of the
      three oscillogenic agents. Moreover, PKC inhibition interferes with the return of
      the intracellular free calcium concentration to basal values during the sperm-
      and ryanodine-induced calcium oscillations, but not during the thimerosal-induced
      calcium oscillations. When the PKC-modulating drugs were applied before any of
      the three oscillogens, the subsequent calcium oscillations were also disturbed.
      However, the first calcium spike induced by spermatozoa and thimerosal was little
      influenced by PKC activation or inhibition. On the other hand, ryanodine failed
      to produce any calcium response when the PKC activity was clamped to a high
      level. These data suggest that sustained high PKC activities impede calcium
      oscillations by interfering with the opening of the ryanodine-sensitive calcium
      release channel, whereas sustained low activities of the enzyme paralyse the
      channel in the open state.

PMID- 9239686
TI  - Analysis of the flow cytometer stain Hoechst 33342 on human spermatozoa.
AB  - Several procedures exist for processing sperm cells for sex preselection. Flow
      cytometric separation using the fluorochrome stain Hoechst 33342, chemically
      known as bisbenzimide, is the most promising. The objective of this study was to
      determine the effect of bisbenzimide on spermatozoa assessed by means of the
      sperm survival test and to analyse the beta-globin gene in sperm DNA after
      exposure to increasing concentrations of bisbenzimide. Donor (n = 16) sperm
      specimens were pooled and washed in a discontinuous Percoll gradient 95:47%,
      divided and incubated in tubes containing bisbenzimide at concentrations 0
      (control), 0.9, 9, 90, 900 and 9000 microM at 25 degrees C and scanned on a
      computer-aided sperm motility analyser at 0, 1, 4 and 24 h. Spermatozoa were also
      incubated in a known mutagen, ethidium bromide, as positive control. After 24 h
      of incubation, the treated sperm cells were processed through DNA extraction and
      polymerase chain reaction (PCR) performed with primers targeting the beta-globin
      gene. The amplified DNA products were analysed for evidence of mutation in 5%
      polyacrylamide gel electrophoresis and 20:80 denaturing gradient gel
      electrophoresis (DGGE) and further confirmed in 30:40 DGGE. The results showed
      complete cessation of motility in sperm incubated in the presence of 900 microM
      or higher concentrations of bisbenzimide. The beat cross frequency sperm
      parameter was significantly different at the 90 microM or higher concentration of
      bisbenzimide compared with the control. At concentrations < 900 microM
      bisbenzimide, there were no differences in the remaining sperm kinematic
      parameters (percentage rapid progressive, percentage total progressive, sperm
      velocities, linearity, straightness, amplitude of lateral head displacement and
      percentage hyperactive motility). PCR and DGGE analyses of spermatozoa treated
      with bisbenzimide showed no evidence of mutation in the representative region of
      the beta-globin gene at concentrations < 900 microM. The data suggest an
      inhibitory effect of bisbenzimide on human sperm motility at 900 microM or higher
      concentrations of bisbenzimide. The decrease in sperm motility and rapid
      progression were not due to changes in pH. Point mutation in the representative
      region of the beta-globin gene in human spermatozoa was detected only at high
      concentrations (> or = 900 microM) of bisbenzimide. The data suggest that
      incubating sperm in low concentrations of bisbenzimide (< 90 microM) for up to 24
      h does not significantly affect all the sperm kinematic parameters including the
      beat cross frequency parameter when compared with the control.

PMID- 9239687
TI  - Preimplantation genetic testing for Marfan syndrome.
AB  - Marfan syndrome (MFS) is an autosomal dominant disease that affects the skeletal,
      ocular and cardiovascular systems. Defects in the gene that codes for fibrillin
      (FBN-1) are responsible for MFS. Here we report the world's first use of
      preimplantation genetic testing (PGT) to achieve a clinical pregnancy and live
      birth of a baby free of a Marfan mutation. One or two blastomeres from each
      embryo were tested for a CA repeat within the FBN-1 gene. The prospective mother
      is homozygous for the CA repeat (2/2) and has two normal copies of the FBN-1
      gene, while the prospective father is heterozygous for the CA repeat (1/2), and
      is affected with the Marfan syndrome. In the father's family, allele 2 segregates
      with the mutated FBN-1 gene. For PGT, any embryo diagnosed as heterozygous for
      the CA repeat (1/2) would be presumed to have inherited normal FBN-1 genes from
      the father and the mother and be unaffected. One in-vitro fertilization (IVF)
      cycle yielded 12 embryos for preimplantation testing; six of the embryos were
      heterozygous for the CA repeat (1/2) and presumed to be free of the Marfan
      mutation. Five of the six embryos were subsequently transferred into the uterus.
      The fetus was tested by chorionic villus sampling and found to be free of the
      Marfan mutation by the same linkage analysis, had a normal fetal echocardiogram,
      and was normal at birth.

PMID- 9239688
TI  - Potential effects of age-associated oxidative stress on mammalian
      oocytes/embryos.
AB  - This bioessay aims to explain the different effects of maternal ageing and
      postovulatory oocyte ageing on mammalian oocytes/embryos under the scope of 'the
      oxygen radical-mitochondrial injury hypothesis of ageing'. This hypothesis
      assumes a key role in the senescent process of oxygen radical damage to
      mitochondrial DNA, proteins and lipids. It is proposed that a decrease in
      intracellular ATP concentrations and glutathione (GSH)/glutathione disulphide
      (GSSG) ratio together with a concomitant increase in cytosolic Ca2+ are major
      factors causing the observed detrimental effects of ageing on cytoskeletal
      fibres, fertilization and embryo development.

PMID- 9239689
TI  - The prolactin inhibition of follicle-stimulating hormone-induced aromatase
      activity in cultured rat granulosa cells is in part tyrosine kinase and protein
      kinase-C dependent.
AB  - The inhibitory actions of prolactin on gonadal steroidogenesis have been reported
      in different species and under a variety of experimental approaches. In this
      study, the mechanisms of the in-vitro effects of human prolactin (hPRL) on human
      follicle stimulating hormone (hFSH)-induced aromatase activity were determined
      using cultured granulosa cells from diethylstilboestrol (DES)-primed immature
      rats. Human PRL caused a dose-dependent decrease in hFSH-induced 17 beta
      oestradiol production, even when cells were cultured in the presence of a cAMP
      analogue (8-Br-cAMP). These effects of hPRL appeared to be specific, since
      addition of an anti-rat PRL receptor monoclonal antibody (mAb) mimicked the hPRL
      inhibitory effect upon steroidogenesis in rat granulosa cells. In order to assess
      the importance of tyrosine kinase and protein kinase-C activation in the hPRL
      inhibitory effects upon oestrogen biosynthesis, cells were cultured in the
      presence of kinase inhibitors. The results showed that addition of genistein or
      staurosporine (a tyrosine kinase and protein kinase-C antagonist respectively) to
      cultured granulosa cells resulted in potent inhibition of hPRL actions upon hFSH
      induced aromatization in a dose-dependent manner. These observations suggest that
      tyrosine kinase and protein kinase-C activation are involved in the biochemical
      events leading to hPRL inhibitory effects at the gonadal level.

PMID- 9239690
TI  - Effects of gamma-aminobutyric acid on human sperm motility and hyperactivation.
AB  - This study was undertaken to evaluate the effects of gamma-aminobutyric acid
      (GABA) and GABAergic agonists and antagonists on sperm kinematic parameters and
      hyperactivation, evaluated by a computer-assisted semen analysis (CASA) system,
      and intracellular cAMP content in 22 normozoospermic semen samples. Because of
      the possible interaction of progesterone with the GABAA receptor, we also
      evaluated the effects of progesterone on these parameters. GABA increased beat
      cross frequency, curvilinear velocity (VCL), the percentage of spermatozoa moving
      with an average path velocity > 10 microns/s (active) and hyperactivation, and
      decreased linearity and straightness. Bicuculline, a GABAA receptor antagonist,
      antagonized the effects of GABA on all these parameters except the percentage of
      active spermatozoa. Muscimol, a GABAA receptor agonist, increased VCL, the
      percentage of active spermatozoa, and hyperactivation by about the same extent as
      GABA, suggesting the involvement of the GABAA receptor. However, the GABAB
      receptor also seems to mediate some of the effects of GABA, because baclofen, a
      selective agonist for this receptor, increased significantly the percentage of
      active spermatozoa and hyperactivation. The effect of baclofen on this latter
      parameter was, however, less pronounced than that obtained with GABA or muscimol.
      Progesterone had the same effects as GABA on sperm kinematic parameters and
      hyperactivation and the simultaneous presence of both compounds was not more
      effective than each single one. GABA and progesterone did not have any effect on
      intracellular cAMP content. In conclusion, GABA modulated sperm kinematic
      parameters and increased hyperactivation. These effects have the same magnitude
      of those produced by progesterone and seem to be mediated mainly by the GABAA
      receptor. We speculate that GABA may be a physiological regulator of sperm
      function.

PMID- 9239691
TI  - alpha-Tocopherol in human spermatozoa and seminal plasma: relationships with
      motility, antioxidant enzymes and leukocytes.
AB  - The chain-breaking antioxidant alpha-tocopherol has not been reported to be
      present in mammalian spermatozoa, unlike other cell types where it contributes to
      cell integrity and function. Semen samples obtained from 36 male partners of
      infertile couples during infertility investigations were analysed for alpha
      tocopherol content of seminal plasma and spermatozoa, and the superoxide
      dismutase and glutathione peroxidase activities of spermatozoa were determined
      concomitantly with routine semen analysis. A wide range of alpha-tocopherol
      concentrations was detected in human spermatozoa (85 +/- 51 ng/10(8) spermatozoa,
      range 10-245). The concentration of alpha-tocopherol in spermatozoa was not found
      to be significantly related to the concentration or the total amount of alpha
      tocopherol in seminal plasma. The percentage of motile spermatozoa was
      significantly related to sperm alpha-tocopherol content (r = 0.84, P < 0.001).
      alpha-tocopherol concentration and superoxide dismutase and glutathione
      peroxidase activities of spermatozoa were significantly elevated when the semen
      samples contained < 10(6) leukocytes/ml (mean +/- SD, 94 +/- 53 compared with 54
      +/- 29 ng/10(8) spermatozoa, P < 0.02, 1.15 +/- 0.41 compared with 0.77 +/- 0.30
      IU/10(8) spermatozoa, P < 0.02 and 60 +/- 26 compared with 30 +/- 14 spermatozoa
      mlU/10(8) spermatozoa, P < 0.005 respectively). From these results, it is
      suggested that alpha-tocopherol might play a role in association with antioxidant
      enzymes, for preserving the functional competence of spermatozoa subjected to an
      oxidative attack.

PMID- 9239692
TI  - Relationship between the expression of cyclins/cyclin-dependent kinases and sex
      steroid receptors/Ki67 in normal human endometrial glands and stroma during the
      menstrual cycle.
AB  - Cell cycle regulatory molecules were analysed in normal human endometrial tissue
      using antibodies against cyclins D1, E, A, and B1 and cyclin-dependent kinases
      (CDKs) cdk4, cdk2, and cdc2. The expression of these regulatory molecules in
      gland cells and stromal cells was compared with the expression of oestrogen
      receptors (ER), progesterone receptors (PR), and Ki67 (a growth-related
      molecule). In general, a substantially higher percentage of the gland cells
      stained positive for cyclins and CDKs during the proliferative phase of the
      menstrual cycle. Cyclin E, cdk2 and/or cdk4 were especially apparent in the
      cytoplasm of most of the gland cells as well as in the stromal cells. In
      contrast, most of the regulatory molecules were undetectable in the gland cells
      by the end of the secretory phase of the cycle, but they did not decline in the
      stromal cells. The data also revealed that ER, PR, and Ki67 in both gland cells
      and stromal cells follow the same basic pattern of expression as the cyclins and
      CDKs. These results suggest that cyclins and CDKs are functionally involved in
      the rhythmic proliferation of normal human endometrial tissue, and the action of
      these agents may be related to the endometrial levels of sex steroids and Ki67.

PMID- 9239693
TI  - Immunocytochemical localization and expression of E-cadherin and beta-catenin in
      the human corpus luteum.
AB  - We have previously shown that the protein connexin-43 which forms the connexons
      in gap junctions is present in the human corpus luteum. Abundant expression of
      connexin-43 is seen in the mid-luteal phase corpora lutea. Since the formation of
      gap junctions in a tissue requires the presence of adherens junctions formed by
      the cadherins, our aim in these studies was firstly to localize
      immunocytochemically E-cadherin and beta-catenin (a cytoplasmic protein
      associated with E-cadherin) in the human corpus luteum, and secondly to determine
      the concentrations of these proteins in the early, mid- and late luteal phase
      human corpora lutea. E-cadherin was localized to the periphery of luteal cells
      and was not detected in non-luteal tissue. beta-catenin was observed in the
      cytoplasm of the luteal cells. Abundant expression of E-cadherin was observed by
      Western analysis in the early luteal phase and the level of expression was
      significantly different from that observed in the mid- and late luteal phase
      corpora lutea. In contrast the concentrations of beta-catenin were higher in the
      mid-luteal phase compared to the early luteal phase. The differential expression
      of the cell adhesion molecule E-cadherin suggests that it may play a significant
      role in cell-to-cell communication in the corpus luteum, and in the cyclic
      development and demise of this tissue.

PMID- 9239694
TI  - Glycodelin from seminal plasma is a differentially glycosylated form of
      contraceptive glycodelin-A.
AB  - Glycodelin-A is a human amniotic fluid-derived glycoprotein with contraceptive
      and immunosuppressive activities. An immunoreactive form of glycodelin was
      detected in seminal plasma over a decade ago, but definitive characterization of
      this glycoprotein was not pursued. We considered it unlikely that the seminal
      plasma of fertile men would contain an appreciable amount of contraceptive
      glycodelin-A. To address this issue we purified seminal plasma glycodelin
      (glycodelin-S) and performed comparative studies with glycodelin-A. Glycodelin-S
      behaved differently when compared with glycodelin-A during sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing
      but identically after enzymatic deglycosylation. N-terminal sequencing of
      glycodelin-A and glycodelin-S gave identical results, and digestion with trypsin
      gave identical peptide fragments. The glycoproteins were also found to be
      indistinguishable from each other based upon immunological analyses. These
      results indicate that glycodelin-S and glycodelin-A have similar overall protein
      structure, suggesting the likelihood that these glycoproteins are differentially
      glycosylated forms of very similar proteins. This latter possibility is supported
      by lectin binding studies indicating that, unlike glycodelin-A, glycodelin-S does
      not manifest any affinity for lectins from Wisteria floribunda or Sambucus nigra.
      The results of sugar analysis and neuraminidase digestion also lead us to
      conclude that glycodelin-S and glycodelin-A are differentially glycosylated forms
      of similar proteins. Our evidence indicates that glycodelin-A mediated its
      biological activities via its unusual oligosaccharide sequences that are not
      associated with glycodelin-S. In lectin-immunoassay no appreciable amount of
      contraceptive glycodelin-A was found in the 22 seminal plasma samples studied.

PMID- 9239695
TI  - The role of carbohydrate in sperm-ZP3 adhesion.

PMID- 9239696
TI  - Polymerase chain reaction screening for Y chromosome microdeletions: a first step
      towards the diagnosis of genetically-determined spermatogenic failure in men.
AB  - Overall, approximately 11% of men attending infertility clinics suffer
      unexplained oligo- or azoospermia. Cytogenetic observations of loss of the distal
      portion of the Y chromosome long arm (Yq) were found to be associated with
      disrupted spermatogenesis. The existence of a gene locus involved in the
      regulation of spermatogenesis, the azoospermia factor (AZF), was thus postulated.
      It is suggested that microdeletions, or mutations, at the AZF locus could result
      in impaired spermatogenesis in chromosomally normal men. In order to test this
      hypothesis we have carried out Y chromosome genetic screening of 100 oligo- or
      azoospermic 46XY patients. We have also assessed phenotype/genotype relationships
      in those patients whose infertility has an underlying genetic aetiology. Patients
      were screened by polymerase chain reaction (PCR) with a set of Y chromosome
      specific sequence tagged sites (STS) for submicroscopic deletions of their Y
      chromosome. Our results show that as many as 8% of cases of unexplained male
      infertility may have an underlying genetic aetiology related to microdeletions in
      two specific regions of the Y chromosome. Positive results from such a screen
      will be important when deciding the suitability of a patient for assisted
      conception schemes such as intracytoplasmic sperm injection.

PMID- 9239698
TI  - Expression and activity of hexokinase in the early mouse embryo.
AB  - The maximal activity and Michaelis constant, KM, of hexokinase have been measured
      in the peri-implantation mouse embryo using an ultramicrofluorescence technique.
      In addition, transcript detection of the predominant isoenzyme hexokinase I has
      been determined in single preimplantation mouse embryos at successive stages of
      development using reverse transcriptase-mediated cDNA amplification. Maximal
      hexokinase activity decreased dramatically peri-implantation, from 0.97 +/- 0.19
      nmol/microgram protein/h at the blastocyst stage to 0.31 +/- 0.05 nmol/microgram
      protein/h on day 6.5. The KM remained relatively low and constant over this
      period (0.23-0.39 mM), indicating the absence of the hexokinase type IV
      isoenzyme. The pattern of hexokinase activity resembled that of glucose
      consumption suggesting a possible regulatory role for the enzyme during this
      period of development. Hexokinase I mRNA was detected in the oocyte and all
      preimplantation stages of development. The blastocyst polymerase chain reaction
      (PCR) product, when cloned and sequenced was found to be 98% homologous with
      mouse tumour hexokinase I. Taken together, these data suggest that the hexokinase
      gene is not under transcriptional control during early mouse embryo development
      but plays a significant role in the regulation of glucose consumption. A role for
      hexokinase in the phosphate-induced inhibition of early embryo development is
      also proposed.

PMID- 9239697
TI  - A factor secreted by human embryo stimulates cytokine release by uterine mast
      cell.
AB  - The existence of a biochemical network of embryo-maternal communication implies
      that various secreted molecules constitute a signal-response mechanism, important
      for the process of embryo implantation in mammals. Here we report the
      purification of a protein with an apparent molecular weight of 136 kDa,
      responsible for a 2000-fold increase in embryo-derived histamine-releasing factor
      (EHRF) activity. This protein, purified from medium from the in-vitro culture of
      2-8-cell human embryos, by means of affinity chromatography, was capable of
      binding immunoglobulin (Ig)E as demonstrated by immunoblotting and enzyme-linked
      immunosorbent assays. We found EHRF was capable of inducing release of histamine
      and cytokines in vitro from rat uterine tissue, collected on day 4 of pregnancy
      (preimplantation stage of embryo development). When EHRF was used as a
      secretagogue, granulocyte macrophage-colony stimulating factor (GM-CSF) release
      increased from 3 to 55 pg/g (P < 0.01) and tumour necrosis factor-alpha (TNF
      alpha) release increased from 0 to 2.1 ng/g (P < 0.01), as detected by enzyme
      linked immunosorbent assay. A simple method was used to purify uterine mast cells
      using an IgE-Sepharose affinity chromatography column and the purity (90%) was
      checked with Dynabeads coupled to specific rat IgE antibody. When purified mast
      cells were stimulated with EHRF in the same way as the uterine explants, a
      similar pattern of GM-CSF and TNF-alpha release was obtained. We also describe
      the reverse transcription-polymerase chain reaction (RT-PCR) of GM-CSF and TNF
      alpha mRNA from purified uterine mast cells. On day 4 of pregnancy only the mRNA
      of TNF-alpha was found and this increased after stimulation with the EHRF. In
      conclusion, the data presented suggest that uterine mast cells isolated during
      the preimplantation stage release cytokines in vitro following interaction with
      an embryo factor.

PMID- 9239699
TI  - Recombinant human luteinizing hormone: a partial physicochemical, biological and
      immunological characterization.
AB  - The aim of this study was to partially characterize the glycoform composition of
      a recombinant human luteinizing hormone preparation (rhLH; Serono), an early
      version of the material (LHadi) which is currently being assessed for clinical
      application. Specifically, the charge (pl) and internal carbohydrate complexity
      of this rhLH was examined and compared with that of an alternative commercially
      available form of recombinant LH (Crystal Chem) and a pituitary International
      Reference Preparation (IRP). All preparations were separated by charge by
      chromatofocusing them on a pH gradient (7-4) using a 4 ml mono-P column is
      conjunction with a fast performance liquid chromatography system and by
      complexity of the oligosaccharide structures using concanavalin A (con-A) lectin
      affinity chromatography. LH in both the unfractionated and fractionated material
      was assessed by immunoradiometric assay (IRMA, I-LH) and by the in-vitro Leydig
      cell bioassay (B-LH). Both assays were calibrated against IRP 80/552. The in
      vitro biopotency of the preparations was 18187 (Serono rhLH), 12063 (Crystal Chem
      rhLH) and 6658 (80/552) IU/mg; biological:immunological ratios were 1.14
      (80/552), 1.90 (Crystal Chem rhLH) and 1.99 (Serono rhLH). However, similar
      qualitative data were obtained by both bioassay and immunoradiometric assay
      following fractionation, with the median pl of the bioactive LH in the
      preparations being 5.5 (24% > pH 6), 5.52 (18% > pH 6) and 4.97 (0% > pH 6) for
      the Serono, Crystal Chem and pituitary preparations respectively. Further all
      three contain < 1% of the complex carbohydrate structures and between 36-44% and
      56-63% of the intermediate and simple forms of bioactive LH. In conclusion, the
      Serono recombinant LH preparation has a higher in-vitro bioactivity and is more
      basic than the other two preparations although the complexity of its carbohydrate
      moities appears to be similar.

PMID- 9239701
TI  - Alternative pathways of acrosome reaction induction.

PMID- 9239700
TI  - Internal carbohydrate complexity of the oligosaccharide chains of recombinant
      human follicle stimulating hormone (Puregon, Org 32489): a comparison with
      Metrodin and Metrodin-HP.
AB  - Glycoforms of recombinant human follicle stimulating hormone (rhFSH) (Org 32489,
      Puregon) were characterized using concanavalin A lectin affinity chromatography
      to reveal information about the internal carbohydrate complexity (extent of
      carbohydrate side-chain branching) of the preparations. The rhFSH glycoforms were
      measured by radioimmunoassay and a two-site immunoradiometric assay and compared
      with those in two urinary preparations (Metrodin and Metrodin-HP) used in
      assisted reproduction programmes and a urinary FSH international standard 70/45
      (uFSH IS 70/45). Similar data were obtained with both assays; rhFSH had 6%
      complex internal carbohydrate structures compared with 22-27% for Metrodin,
      Metrodin-HP and uFSH. The proportion of simple carbohydrate structures was also
      different, with rhFSH having 18.5 compared with 4.5-9.3% for Metrodin, Metrodin
      HP and uFSH. A linear relationship was observed between the percentage glycoforms
      with an isoelectric point (pl) < 4 and the log percentage simple forms
      (logarithmic regression; r = 0.93) indicating a direct relationship between
      carbohydrate complexity and charge heterogeneity. In summary, rhFSH contains
      fewer complex forms and an increased proportion of simple carbohydrate structures
      in comparison with Metrodin, Metrodin-HP and IS 70/45.

PMID- 9239702
TI  - Calcium influx pathways in human spermatozoa.

PMID- 9239703
TI  - Viewing AIDS from a glycobiological perspective: potential linkages to the human
      fetoembryonic defence system hypothesis.
AB  - The primary molecular changes that lead to development of acquired
      immunodeficiency syndrome (AIDS) are very poorly understood, as are the
      mechanisms underlying the protection of the developing human from the maternal
      immune response. Recent data that the human immunodeficiency virus (HIV) may be
      using the glycosylation system of the T lymphocytes to acquire glycans for its
      glycoproteins that enable it to disrupt carbohydrate dependent immune cell
      interactions or induce aberrant immune reactions. Consistent with this
      hypothesis, gp120 from HIV infected human H9 lymphoblastoid cells expresses
      biantennary N-linked glycans with a bisecting GlcNAc sequence on 11% of their
      total oligosaccharides. This specific carbohydrate sequence has recently been
      shown to protect K562 erythroleukemic cells from natural killer (NK) cell
      responses when presented on the cell surface. We have recently demonstrated that
      bisecting biantennary type N-linked glycans are also expressed on the human zona
      pellucida (ZP); previous lectin binding studies indicate that is also expressed
      on human spermatozoa. Thus both the human gametes and HIV produced by H9 cells
      carry this same protective carbohydrate epitope on their outer surfaces. Human
      alpha-fetoprotein expressed in the developing human also carries the bisecting
      GlcNAc sequence, indicating that it may be suppressing the emerging fetal immune
      response by using its carbohydrate sequence as a functional group. We have
      suggested that the developing human and the gametes are also protected by soluble
      immunosuppressive glycoproteins found in the amniotic fluid and seminal plasma
      known as glycodelin-A (GdA) and glycodelin-S (GdS) respectively. Structural
      analysis of their N-linked oligosaccharides combined with other functional
      studies suggest that GdA and GdS employ their very unusual carbohydrate sequences
      as functional groups that enable them to manifest their immunosuppressive
      activities. GdA and GdS are significant components of our recently proposed model
      for the protection of the developing human and gametes designated the human
      fetoembryonic defence system hypothesis. A striking relationship now emerging is
      that the same unusual carbohydrate sequences associated with these
      immunosuppressive glycodelins are also specifically expressed on intravascular
      helminthic parasites, Helicobacter pylori, human tumour cells, and HIV infected T
      lymphocytes. The information presented in this review suggests that two new
      corollaries should be added to our recently proposed defence system hypothesis:
      (i) mimicry or acquisition of glycans that are used in this protective system by
      pathogens or tumour cells may enable them to either subvert or misdirect the
      human immune response, thereby greatly increasing their pathogenicity; and (ii)
      expression of glycoproteins used in this system by normal cells and tissues
      outside the reproductive system may protect them from immune responses,
      especially in those cases where major histocompatibility recognition is either
      absent or minimal. A better understanding of this hypothesis and its corollaries
      may enable us to address the molecular mechanisms underlying not only AIDS but
      also a host of other very serious pathological conditions in the human.

PMID- 9239704
TI  - Haploid transcripts persist in mature human spermatozoa.
AB  - Mammalian spermiogenesis is marked by the morphological and functional
      differentiation of round haploid spermatids into mature spermatozoa. A molecular
      restructuring of the chromatin accompanies this process facilitated by the
      transition proteins and protamines which compact and condense the genetic
      material within the developing spermatid. Previous studies from this laboratory
      have demonstrated that human protamines PRM1, PRM2 and transition protein TNP2
      transcripts are associated with round and elongating spermatids. Extending this
      investigation, we examined the occurrence of these transcripts in mature
      spermatozoa by in-situ hybridization analysis using [35S]-labelled cRNA probes.
      These results demonstrate that PRM1, PRM2 and TNP2 haploid-specific transcripts
      are present in mature spermatozoa. Quantitative analysis of the localized signal
      also indicates that the PRM1, PRM2 and TNP2 transcripts persist at a similar
      ratio to that previously described for these transcripts in human testes, i.e.
      PRM2 > PRM1 approximately equal to TNP2. The persistence of these transcripts in
      mature spermatozoa warrants further investigation.

PMID- 9239705
TI  - Hormonal regulation of expression of messenger RNA encoding insulin-like growth
      factor binding proteins in human endometrial stromal cells cultured in vitro.
AB  - To investigate the presence of messenger RNA (mRNA) encoding insulin-like growth
      factor binding proteins (IGFBP) in human secretory endometrial stromal cells
      cultured in vitro, total cellular mRNA and protein extracted from cells treated
      with various hormones were detected and identified by Northern and Western
      blotting techniques respectively. Northern blot analysis detected 1.4 and 2.5
      kilobase (kb) mRNA transcripts for IGFBP-2 and IGFBP-3 respectively, in both
      control and progestin-treated human endometrial stromal cells in vitro. However,
      the 1.5 kb mRNA transcript of IGFBP-1 was detected only in progestin-treated
      cells but not in the controls. Progestin alone markedly stimulated cellular BP-1
      protein and mRNA, but only moderately stimulated cellular IGFBP-2 and IGFBP-3
      protein mRNA in a dose-dependent fashion. Adding relaxin at the same time as
      progestin further enhanced the stimulatory effects of progesterone. Oestradiol
      had a stimulatory effect on cellular IGFBP-2 mRNA, but had an inhibitory effect
      on protein and mRNA of IGFBP-3, also in a dose-dependent fashion. In general, for
      each specific binding protein, the amount of cellular mRNA correlated well with
      the amount of cellular protein. Therefore, IGFBP protein and mRNA transcript in
      human secretory endometrial stromal cells appears to be under hormonal influence.
      These hormones may control the synthesis of IGFBPs at the transcription rather
      than the translation level.

PMID- 9239706
TI  - Matrix metalloproteinases as mediators of reproductive function.
AB  - The organs of the adult reproductive system can undergo extensive remodelling,
      experiencing rapid changes in tissue mass and function. Much of this matrix
      remodelling is attributed to the action of matrix metalloproteinases. Matrix
      metalloproteinase family members are expressed in a highly-regulated manner in
      many reproductive processes, including menstruation, ovulation, implantation, and
      uterine, breast, and prostate involution. Metalloproteinase concentrations and
      activity can be regulated by reproductive hormones, as well as by growth factors
      and cytokines that participate in reproductive events. In addition to playing a
      role in the loss of connective tissue mass, the metalloproteinases can influence
      the phenotype of the cellular components of the tissues, altering basic cellular
      functions such as proliferation, differentiation, and apoptosis. This review
      focuses on the expression of matrix metalloproteinases in reproductive tissues,
      and discusses the evidence supporting a role for these enzymes in modulating the
      structure and function of reproductive organs.

PMID- 9239707
TI  - Evaluation of chromatin condensation in human spermatozoa: a flow cytometric
      assay using acridine orange staining.
AB  - The quality of sperm chromatin is an important factor in fertilization and is
      especially critical where one spermatozoon is artificially selected for
      fertilizing an egg (as in intracytoplasmic sperm injection). In this study, flow
      cytometry after staining of human spermatozoa with Acridine Orange was used to
      study chromatin structure. A method is described for estimating the percentage of
      cells in a human sperm sample that have completed epididymal maturation in regard
      to chromatin condensation. Of the 121 samples of the semen that were examined,
      nine contained a higher percentage of hypocondensed spermatozoa and six samples
      contained elevated amounts of hypercondensed spermatozoa. In addition to
      aberrancies in chromatin condensation other defects showed up as satellite
      populations of spermatozoa with higher than normal ratios of red/green
      fluorescence after Acridine Orange staining. Such defects were found in 15 semen
      samples. The use of swim-up and Percoll gradient centrifugation methods was shown
      to improve the percentage of spermatozoa with normal chromatin structure in some
      samples with poor initial quality.

PMID- 9239708
TI  - Absence of DAZ gene mutations in cases of non-obstructed azoospermia.
AB  - Sequenced-tagged site (STS) analysis of the Y chromosome long arm (Yq) of
      azoospermic males has identified a minimum common deleted region of several
      hundred kilobases in approximately 13% of cases. A candidate azoospermia gene,
      DAZ (deleted in azoospermia), has been isolated from this region. DAZ has also
      been shown to be absent in severely oligozoospermic males albeit at a much lower
      frequency. These data, although highly suggestive, do not constitute formal proof
      that DAZ actually plays a role in azoospermia, as no small intragenic deletions,
      rearrangements or point mutations in the gene have been found. In this study we
      report the screening of DNA from 168 azoospermic/oligospermic males for the
      presence of the DAZ gene. Deletions involving DAZ were detected in five out of 43
      (11.6%) azoospermic males whereas none were found in the remaining 125
      oligospermic patients. We present the genomic structure of the 5' end of the DAZ
      gene together with its sequence analysis in 30 non-obstructed azoospermic males.
      No mutations in DAZ were found in any of the patients sequenced. These data
      provide no formal proof that DAZ is AZF. Thus the possibility is still valid that
      another gene(s) mapping to the deletion interval may be responsible for, or
      contribute to, the observed phenotypes. Alternatively, if DAZ is AZF, they
      suggest that the most frequent cause of gene inactivation is via large deletions
      possibly mobilized by Y chromosome repetitive sequences.

PMID- 9239709
TI  - Size differences between human X and Y spermatozoa and prefertilization
      diagnosis.
AB  - Normal human spermatozoa carry either the X or the Y chromosome. The differences
      between X and Y spermatozoa (X and Y haploid cells) may exist in two areas: the
      different chromosomes (i.e. different kinds and numbers of genes) and the
      different sperm structures and functions (i.e. different genetic expression). The
      aim of this study was to determine whether there are any size between X and Y
      spermatozoa and whether sperm size and shape varies between men. Identification
      of the Y (and X inferred) status of individual spermatozoa was carried out by
      polymerase chain reaction (PCR), amplifying the putative testis-determining gene
      (SRY) together with a control gene (ZP3). PCR amplification of 871 out of 895
      (97.3%) single motile spermatozoa showed that 444 (51.0%) were Y and 427 (49.0%)
      were X-bearing spermatozoa. Of 233 normally-shaped but immobilized spermatozoa,
      217 (93.1%) were photographed and measured. Statistically, the length, perimeter
      and area of the sperm heads, and the length of the sperm necks and tails of X
      bearing spermatozoa were significantly larger and longer than those of Y-bearing
      spermatozoa. Some peculiarities (or variations) in the X and Y sperm shape and
      size in individual donors were found. The pre-screening by micro-measurement of
      these specific haploid characteristics of individual spermatozoa in different
      donors, which may be closely related to their different genetic conditions (or
      diseases), may be important in human medicine and animal husbandry, especially in
      sperm prefertilization diagnosis.

PMID- 9239710
TI  - Expression of endothelial and inducible nitric oxide synthase in non-pregnant and
      decidualized human endometrium.
AB  - Immunocytochemistry was used to localize endothelial (eNOS) and inducible (iNOS)
      nitric oxide synthase in human uterine tissues collected at various stages of the
      menstrual cycle, after exposure to exogenous progestagens, and in early
      pregnancy. Endothelial NOS-like immunoreactivity was detected in all specimens in
      endothelial cells lining blood vessels in the myometrium and endometrium, and in
      endometrial glandular epithelial cells. Inducible NOS-like immunoreactivity was
      also demonstrated in glandular epithelial cells. For both eNOS and iNOS there was
      considerable variation in the intensity of epithelial cell staining between
      samples, which was not related to the stage of the menstrual cycle at which the
      tissue was collected. Messenger RNA for eNOS and iNOS was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) using total RNA purified from
      isolated endometrial gland fragments. Immunoreactivity for eNOS and iNOS was not
      present in endometrial stroma throughout the menstrual cycle, but iNOS-like
      immunoreactivity was seen in decidualized stromal cells both following treatment
      with exogenous progestagen (intrauterine L-norgestrel) and in tissues obtained in
      the first trimester of pregnancy. The detection of protein and mRNA for eNOS and
      iNOS in normal human endometrium suggests that NO may play a role in the local
      control of endometrial function.

PMID- 9239711
TI  - Paternal X-chromosome inactivation in human trophoblastic cells.
AB  - Dosage compensation for X-chromosome-linked genes between male and female mammals
      occurs by inactivation of one of the two X chromosomes in the female. In somatic
      cells, either the paternal or the maternal X chromosome is randomly inactivated
      in a given cell. In contrast, in the extra-embryonic tissues of mice, the
      paternally-derived X chromosome is preferentially inactivated. The evidence for
      paternal X-chromosome inactivation in humans is controversial and remains to be
      clarified. In this study, we have developed a sensitive polymerase chain reaction
      (PCR) technique to investigate the methylation pattern of the X-linked androgen
      receptor (AR) gene. The 5' CpG island of this gene is methylated on the inactive
      X chromosome and hypomethylated on the active X chromosome in somatic cells. The
      paternal and the maternal alleles of the AR gene may be distinguished by a
      polymorphism in the number of CAG triplet repeats within the CpG island. As a
      source of human extra-embryonic tissue, we used chorionic villus (CV) samples
      from female conceptuses of 10-12 weeks gestation. From a tiny branch of a CV
      sample, two distinct cell lineages, the trophoblastic and mesodermal lineages,
      were dissected apart by trypsin digestion and micromanipulation and DNA was
      extracted separately from these purified tissues. Digestion of the DNA with the
      methylation-sensitive restriction enzyme, Hpall, followed by PCR amplification
      revealed that the paternal allele is preferentially methylated in trophoblastic
      cells, but not in mesodermal cells. These results strongly suggest that the
      paternal X chromosome is preferentially inactivated in the human extra-embryonic
      tissues early in development.

PMID- 9239712
TI  - Hypothesis to unify an embryonic defence system and HIV infection.

PMID- 9239713
TI  - Developmental changes in calcium content of ultrastructurally distinct
      subcellular compartments of preimplantation human embryos.
AB  - The ultrastructural localization of mobilizable Ca2+ in different subcellular
      compartments of human oocytes and preimplantation embryos was studied using the
      potassium-pyroantimonate technique and transmission electron microscopy; the
      specificity was confirmed by chelation experiments and X-ray microanalysis. In
      unfertilized oocytes, Ca2+ was detected in small vesicles beneath the plasma
      membrane as well as in other forms of smooth endoplasmic reticulum (SER) and in
      mitochondria but not in cortical granules. In pronuclear zygotes and blastomeres
      of cleaving embryos, Ca(2+)-rich vesicles were no longer present close to the
      plasma membrane, and the entire periphery was poor in Ca(2+)-containing
      organelles which, however, were abundant in the perinuclear region. The uneven
      Ca2+ loading of SER and mitochondria from the pronuclear stage onwards suggests
      that Ca2+ release from both these types of organelle contributes to the embryonic
      Ca2+ signals. During mitosis, less Ca2+ was detected with organelles, but the
      antimonate reaction product was more abundant in the cytosol. These data suggest
      that, in addition to different forms of SER, mitochondria also act as a source of
      mobilizable Ca2+ in preimplantation human embryos. The previously described
      developmental and cell cycle related changes in the characteristics of Ca2+
      signals are associated with the redistribution and structural reorganization of
      these organelles.

PMID- 9239714
TI  - Effects of a GnRH analogue on human smooth muscle cells cultured from normal
      myometrial and from uterine leiomyomal tissues.
AB  - Leiomyomas are tumours of uterine smooth muscle tissue that are oestrogen and
      progesterone dependent. When explants of these tumours were grown in culture, the
      proliferating tissue formed characteristic ball-like aggregates (BLA), rather
      than the usual hill and valley (HV) pattern of growth of normal myometrial tissue
      in culture. Immunocytochemical staining with fluorescein isothiocyanate (FITC)
      labelled gonadotrophin-releasing hormone (GnRH) revealed that both myometrial and
      leiomyomal cells have membrane receptors for this hypothalamic releasing hormone.
      Furthermore, polymerase chain reactions (PCR) with primer sets that were specific
      for GnRH receptor mRNA, as well as GnRH mRNA, showed that transcripts for both of
      these nucleic acids are present in myometrial and leiomyomal tissues. The
      treatment of cultured explants of leiomyomal tissue with a GnRH analogue
      (buserelin, HOE766) diminished the formation of BLA, but this synthetic hormone
      had only a moderate effect on the HV topography of normal myometrial tissue. A
      colorimetric assay indicated that GnRHa inhibited cell proliferation in
      leiomyomal tissue in a dose-dependent manner. Western blotting, to detect the
      expression of G1 phase cell cycle-related gene products, showed that cyclin E and
      p33cdk2 formation in leiomyomas were inhibited by high concentrations of GnRHa.
      In conclusion, GnRHa might suppress leiomyomal growth by interfering with the
      expression of cell cycle factors.

PMID- 9239715
TI  - Expression of luteinizing hormone/human chorionic gonadotrophin (LH/HCG) receptor
      mRNA in the human ovary.
AB  - The gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone
      (LH) are key hormones in the regulation of ovarian function. In the present
      study, the expression of LH/human chorionic gonadotrophin (HCG) receptor mRNAs in
      the human ovary was examined. Northern blot analysis was used to measure relative
      amounts of LH/HCG receptor mRNA, and in-situ hybridization was used to localize
      LH/HCG receptor transcripts. Northern blot analysis of human ovaries detected
      three transcripts (5.4, 3.6 and 2.4 kb) for the LH/HCG receptor. LH/HCG receptor
      mRNA concentrations increased from preovulatory follicles to the corpus luteum of
      the midluteal phase, and decreased at the late luteal phase. Using in-situ
      hybridization, LH/HCG receptor mRNA was located predominantly in granulosa cells
      in the same follicle. Cloning of the human LH/HCG receptor cDNA previously
      revealed the existence of two alternative forms of the receptor differing by the
      presence (HLH-Ra) and absence (HLH-Rb) of 62 amino acids by exon 9. We have
      studied the functional significance of these receptor isoforms and have confirmed
      that they are generated by alternative splicing. A reverse transcription
      polymerase chain reaction amplification was used to detect different isoforms of
      LH receptor mRNAs in ovary and placenta. The expression of the two mRNA forms of
      LH/HCG receptor were detected in ovary, and at very low concentrations in
      placenta. Treatment with HCG caused a dose-dependent increase in cAMP production
      with an initial response evident at approximately 1 ng/ml HCG in COS-7 cells
      expressing HLH-Ra. However, a complete loss of signal transduction was found in
      cells transfected with the truncated HLH-Rb.

PMID- 9239717
TI  - Developmental functions of mammalian Hox genes.
AB  - The structure of the four murine Hox complexes and the co-ordinate expression
      patterns of Hox genes have been elucidated for almost a decade. However, clues
      about their developmental functions have been recently uncovered from the
      analysis of loss-of-function mutants generated by the gene targeting technique,
      as well as from transgenic mice with altered Hox gene expression domains. The
      'anterior' Hox genes control the morphogenetic programme of specific hindbrain
      segments (rhombomeres) or pharyngeal arch neural crest derivatives. Various
      studies indicate that Hox gene products act in a region-specific, combinatorial
      and partly redundant manner to specify the identities of developing vertebrae. In
      addition, 'posterior' HoxA and HoxD genes act coordinately to control the growth
      and morphogenesis of skeletal structures along the proximodistal axis of
      developing limbs. Studies in other vertebrate model systems suggest that the
      evolution of Hox gene functions has allowed for the acquisition of specific
      morphological features along both the vertebral column and limbs of tetrapods.
      Gene targeting studies have also revealed region-specific functions of Hox genes
      along the developing digestive and genito-urinary tracts.

PMID- 9239716
TI  - Localization of a 25 kDa human sperm surface protein: its role in in-vitro human
      sperm capacitation.
AB  - A human endometrial sialic acid-binding glycoprotein (SABP) binds specifically to
      a 25 kDa protein on the plasma membranes of human non-capacitated sperm heads. In
      vitro labelling of the sperm surface sialoglycoconjugates and subsequent
      incubation with SABP, suggests removal of some sialoglycoconjugate moieties from
      the sperm surface upon interaction with SABP. SABP also induces the exposure of
      mannose ligand receptors on the sperm surface and increases the production of
      superoxide anion (O2-).

PMID- 9239718
TI  - Mitochondrial disorders.
AB  - Mitochondria, the organelles devoted to energy production, have unique genetic
      features. They possess their own genome encoding several subunits of the
      respiratory chain, the majority of which are encoded by nuclear DNA, as well as
      factors involved in replication, transcription and translation of mitochondrial
      DNA. In the past few years, molecular lesions of mitochondrial DNA have been
      reported with increasing frequency as a source of human disorders. Several
      mutations of mitochondrial DNA, either as sporadic large scale rearrangements
      (deletions, duplications) or maternally-inherited point mutations, have been
      associated with well defined clinical syndromes. Furthermore, because of the
      nuclear DNA contribution to the synthesis of respiratory chain enzymes,
      phenotypes transmitted as Mendelian traits have also been identified and
      associated with qualitative (multiple deletions) and quantitative (depletion)
      lesions of the mitochondrial genome. The clinical manifestations of mitochondrial
      DNA mutations are extremely heterogeneous, ranging from myopathies,
      encephalomyopathies, cardiopathies, to complex multisystem syndromes. Clinical,
      morphological, biochemical and molecular genetic data are necessary for
      diagnosis. The recent advances in genetic studies provide both diagnostic tools
      and new pathogenetic insights into this rapidly expanding area of human
      pathology.

PMID- 9239719
TI  - Archival fixed and analysed preimplantation human embryonic cells: a DNA resource
      for retrospective PCR analysis at the cellular level.
AB  - Biopsies of human embryonic cell preparations previously analysed by cytogenetic
      and/or fluorescent in-situ hybridization (FISH) chromosome probes provide a
      unique reference DNA resource for the archival preimplantation genetic diagnosis
      (PGD) of the transferred embryo. DNA polymerase chain reaction (PCR) may be
      utilized on these fixed cell preparations to verify equivocal FISH/PGD results.
      Retrospective PCR screens of the genotype of biopsied embryonic cell(s) may be of
      benefit in the case of a suspected genetic mutation. Currently, carrier detection
      or linkage analysis is often not possible because of early death of the fetus, or
      of patients with a lethal disease. Alternatively, fixed/stained 'failed
      fertilized' oocytes provide a resource to extend genetic analysis to infertile
      patients. A successful research is described which minimizes loss of individual
      analysed fixed/stained oocytes, metaphase chromosomes, and embryonic cell
      samples. Initial DNA amplification takes place in situ using a modified PCR
      protocol. Comparative cellular studies using primer sets previously used for PGD
      analyses show that 65% of the preparations amplified unequivocally using the
      modified protocol and primers for a CA repeat motif gene sequence, in comparison
      with 81% using the original PCR protocol. With further refinement and
      optimization, the methods outlined have the potential to retrospectively screen
      archival fixed chromosomes, gametes, and embryonic cells for clinical
      application, and enable the further study of the fixed human preimplantation
      embryo at the morphological, cell and molecular level.

PMID- 9239720
TI  - Beck-Wiedemann syndrome and Wilms' tumour.
AB  - Patients with rare overgrowth disorders, such as Beck-Wiedemann syndrome and
      Simpson-Golabi-Behmel syndrome, are predisposed to embryonal tumours, including
      Wilms' tumour of the kidney. Therefore, these disorders offer a link between
      hyperplastic growth and cancer. Genetic lesions at chromosome 11p15 have been
      associated with Beck-Wiedemann syndrome and Wilms' tumour for several years and
      the presence of the gene encoding insulin-like growth factor-II (IGF-II) in this
      region has given rise to much speculation over the involvement of this factor in
      these growth defects. This speculation was heightened by genetic evidence for the
      involvement of genomic imprinting in Beck-Wiedemann syndrome and Wilms' tumour,
      combined with the discovery that the IGF-II gene is imprinted. Although there is
      a wealth of evidence linking the IGF signalling pathway with overgrowth and
      cancer, recent progress in the study of 11p15 and developments in our
      understanding of the mechanism of genomic imprinting indicate that additional
      imprinted genes located in this region also contribute to these growth disorders.

PMID- 9239722
TI  - Inhibition of transforming growth factor-beta 1 alters the growth, anchor
      dependent cell aggregation and integrin mRNA expression in human promonocytes:
      implications for endometriosis and peritoneal adhesion formation.
AB  - Transforming growth factor beta (TGF-beta) is a major secretory product of
      macrophages which, through autocrine/paracrine pathways, play a central role in
      normal reproductive tissues as well as in disorders such as endometriosis and
      intraperitoneal adhesion formation. Using TGF-beta antisense oligonucleotides and
      U937 cells (a promonocytic human cell line) as an in-vitro model, the present
      study examined the autocrine mediated action of TGF-beta 1 on proliferation,
      anchor-dependent and -independent cell aggregation and expression of several
      mRNAs of cell surface adhesion molecules including integrins and platelet
      endothelial cell adhesion molecule (PECAM-1). Northern blot analysis and enzyme
      linked inmmunosorbent assay (ELISA) revealed that treatment with TGF-beta 1
      antisense, but not sense or nonsense oligomers, in a dose-dependent manner (0.1
      10 microM) down-regulated the expression of TGF-beta 1 mRNA and protein to
      undetectable amounts at the highest antisense concentration. TGF-beta 1 antisense
      at < 1 mM slightly increased, while at > 3 microM significantly inhibited, the
      rate of DNA synthesis and proliferation of these cells (P < 0.05). Treatment with
      TGF-beta 1 antisense promoted cell aggregation under anchor-independent culture
      conditions (plastic dishes), while it suppressed colony formation under anchor
      dependent culture conditions (soft agar assay). U937 cells expressed alpha 2,
      alpha 3, alpha 4, alpha 5, alpha 6, beta 1 and beta 2 integrin mRNA and PECAM-1
      mRNA, while alpha v, beta 3 and beta 5 integrin mRNA was undetectable. The
      relative amount of alpha 2, alpha 3, alpha 4, alpha 6, beta 1 and beta 2 integrin
      and PECAM-1 mRNA expression were down-regulated in a dose-dependent manner after
      TGF-beta 1 antisense treatment, while alpha 5 integrin mRNA expression was up
      regulated, although it was undetectable at 10 microM antisense. In contrast, TGF
      beta 1 antisense up-regulated beta 3 mRNA expression with maximal effect
      occurring at 10 microM. These results provide evidence that the autocrine loop of
      monocyte/macrophage-derived TGF-beta 1 action is essential for regulation of
      growth, aggregation and the expression of adhesion molecules by these cells. We
      propose that in disorders such as endometriosis and peritoneal fibrous adhesions,
      significantly higher numbers of tissue macrophages with the capacity to express
      excess TGF-beta 1 yield an environment able to promote cell-cell and cell-matrix
      interactions, and thus lead to further complications from these abnormalities. We
      are currently investigating whether site-specific inhibition of TGF-beta using
      antisense strategy is a useful tool for management of these lesions, particularly
      after their post-surgical removal.

PMID- 9239721
TI  - Aberrant expression pattern of gap junction connexins in endometriotic tissues.
AB  - The expression of gap junction connexins (Cx) in the female reproductive tract of
      rodents and in the human endometrium is highly regulated by steroid hormones.
      Here we have investigated the distribution and regulation properties of Cx43,
      Cx26 and Cx32 in the human ectopic endometrium of 41 patients, using
      immunohistochemistry. The biopsies were obtained during the early or late
      follicular phase (26 cases), during the corpus luteum phase (five cases) and
      after a 6 month treatment with a gonadotrophin-releasing hormone (GnRH) agonist
      (three cases) or progestin (seven cases). Aberrant expression of Cx43 was found
      in the epithelium of nearly all endometriotic glands whereas Cx26, typical for
      human uterine epithelium cells, was only detected in 18 cases; in 17 it was co
      expressed with Cx43. The stromal compartment of the tissues did not express any
      connexins investigated. Staining for Cx32 was absent in all endometriotic
      tissues. Strong expression of Cx43 was correlated with a high serum value of 17
      beta-oestradiol, whereas a strong expression of Cx26 was found with high values
      of progesterone mainly in patients after progestin treatment. The epithelium of
      endometriotic implants collected after GnRH agonist treatment expressed Cx26 and
      Cx43 only moderately. The patterns described demonstrate an aberrant connexin
      expression and a different hormonal regulation pattern in endometriotic tissues
      compared to the normal cyclic uterine endometrium, thus indicating a high
      dedifferentiation from the normal situation. However, endometriosis still remains
      a hormonally-dependent benign disease, and hence, can be treated hormonally.

PMID- 9239723
TI  - The pattern of cytokine mRNA expression in ovarian endometriomata.
AB  - Intraovarian cytokines play a pivotal role in the normal growth and development
      of the ovarian follicle. The purpose of this study was to investigate the pattern
      of cytokine mRNA expression in ovarian endometriomata. A total of 10 patients
      with histologically confirmed endometriomata undergoing surgery formed the study
      group while nine patients undergoing sterilization with no evidence of a cyst in
      the ovary formed the control group. Biopsies of the ovary were obtained at
      surgery and stored in liquid nitrogen until processed by reverse transcription
      polymerase chain reaction amplification to identify the presence of mRNA for
      interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor
      alpha (TNF-alpha), and interferon-gamma (IFN-gamma). IL-6 and IL-10 mRNA were
      expressed by nine and seven patients respectively in the endometriosis group
      compared with three and one patients in the control group; this difference was
      significant (P < 0.05). IL-1 alpha mRNA was expressed by seven of 10 patients
      with endometriosis but by only one of the control group; this was again
      significantly different (P < 0.04). Ovarian IL-2 and IL-4 mRNA were not expressed
      in either group. There was no significant difference in the expression of IL-8,
      IL-13, IFN-gamma and TNF-alpha mRNA in the two groups. These findings suggest
      that abnormal local expression of certain cytokines may contribute to the
      development of endometriomata.

PMID- 9239724
TI  - Glycosidic residues involved in human sperm-zona pellucida binding in vitro.
AB  - Glycosidic residues of the mammalian zona pellucida (ZP) are known to be involved
      in sperm binding, suggesting the presence of complementary carbohydrate binding
      sites on spermatozoa. However, in previous studies, in which sperm suspensions
      were incubated with monosaccharides, no inhibitory effect was observed. Results
      of studies in which sperm were treated shortly after swim-up suggest that the use
      of non-capacitated cells may explain the apparently conflicting results. In the
      present report, we studied the effect of preincubation of capacitated spermatozoa
      with different monosaccharides on their ability to bind to ZP. After 5 h under
      capacitating conditions, spermatozoa were incubated in medium with or without a
      monosaccharide, resuspended in fresh medium and used for hemizona (HZ) binding
      assay. When ZH were incubated with spermatozoa treated with N-acetyl-D
      glucosamine, D-mannose, D-fucose, L-fucose or D-galactose, a significant decrease
      in the number of spermatozoa bound was observed (level of inhibition: 62, 58, 82,
      68 and 48% respectively) while treatment of spermatozoa with D-glucose produced
      no inhibition. Sugar treatment neither altered sperm motility nor the rate of
      acrosome reaction. These results suggest that N-acetylglucosamine, mannose,
      fucose and galactose residues are involved in human sperm-zona pellucida binding
      in vitro.

PMID- 9239725
TI  - Gonadotrophin regulation of production of tissue inhibitor of metalloproteinases
      1 by luteinized human granulosa cells: a potential mechanism for luteal rescue.
AB  - Human granulosa cells were maintained in culture with extracellular matrix in the
      presence or absence of human chorionic gonadotrophin (HCG) using a defined
      culture medium. Such cultures are maintained by gonadotrophin in a manner
      suggesting that features of 'luteal rescue' may be occurring in vitro. Western
      analysis of culture medium demonstrated that the granulosa cells produced tissue
      inhibitor of metalloproteinases (TIMP)-1 but not TIMP-2. The presence of TIMP-1
      in cultured cells was also detected immunocytochemically. Immunoassay of TIMP-1
      output revealed that HCG exposure for 7 days caused a 2-fold increase in TIMP-1
      production versus control reaching maximum at approximately 1 ng HCG/ml. The
      sensitivity of this response to HCG was similar to that observed for stimulation
      of progesterone production. Delayed addition of HCG, from day 4 of culture,
      elicited increases in TIMP-1 which were evident within 24 hours, and were not
      explained by changes in cell replication or survival. Removal of HCG from
      cultures previously luteinized with HCG for 6 days resulted in a fall in TIMP-1
      production. Thus TIMP-1 production by luteinized granulosa cells in culture is
      gonadotrophin dependent. We speculate that prolonged cellular function associated
      with 'luteal rescue' may result from increased extracellular matrix stability
      mediated by up-regulation of TIMP-1 production.

PMID- 9239726
TI  - Analysis of stem cell factor for mast cell proliferation in the human myometrium.
AB  - The proliferation and differentiation of human mast cells (MCs) occur under the
      influence of the mitogenic agent known as stem cell factor (SCF). This study
      analyses the distribution of SCF and SCF receptor in human myometrial tissue to
      further the understanding of the role(s) of MCs in the uterus.
      Immunohistochemical staining revealed that the majority of uterine MCs are
      located in close proximity to myometrial smooth muscle cells, and also among
      fibroblast-like spindle shaped cells. RNA extracts from myometrial tissues were
      subjected to reverse transcription. The resulting cDNA population was amplified
      by polymerase chain reaction (PCR) using a pair of 20-mer primers that were
      specific for SCF cDNA. Electrophoresis of the PCR products showed that the
      myometrial tissues contained transcripts for SCF. In-situ reverse transcription
      PCR also revealed the expression of the transcripts for SCF in myometrial smooth
      muscle cells. Furthermore, enzyme-linked immunosorbent assays confirmed that the
      cultured myometrial cells produced SCF. Since immunohistochemical staining
      indicated there are SCF receptors on the surface of myometrial MCs, the results
      suggest that MC proliferation and differentiation in the myometrium is regulated
      by SCF secretion from the uterine smooth muscle cells. The mature MCs might, in
      turn, secrete mediators that influence tissue remodelling during the human
      menstrual cycle.

PMID- 9239727
TI  - The molecular genetics of male infertility.
AB  - The important role of genetic abnormalities in the causation of human male
      infertility is increasingly recognized. While much remains to be learned in this
      fast moving field, considerable progress has been achieved over the past years
      both in the clinical delineation of genetic forms of male infertility and in the
      characterization of the responsible genes and their mutations. We review the
      current state of knowledge on monogenic disorders where male infertility is a
      major and regular feature. Clinical and molecular details are given on a total of
      seventeen such entities. We restrict our survey to disorders that may actually
      come to the clinical attention of the reproductive medicine specialist.

PMID- 9239728
TI  - Comparison of gonosomal aneuploidy in spermatozoa of normal fertile men and those
      with severe male factor detected by in-situ hybridization.
AB  - The purpose of the study was to analyse the frequency of sex-chromosome numerical
      abnormalities in human spermatozoa of infertile men by using a standardized
      experimental protocol of double target in-situ hybridization (ISH). The
      experiments were performed on decondensed sperm heads from 15 infertile patients
      (six cases of unexplained infertility and nine cases of severe
      oligoasthenoteratozoospermia). Three men of proven fertility were used as
      controls. The probes employed recognized the centromeric regions of human X
      chromosome and the long arm of the Y chromosome. In a smaller number of cases,
      additional experiments of double ISH were performed using centromeric probes for
      chromosomes 1 and 17. Signal detection was based on protocols of enzymatic
      cytochemical reactions. A total of 24,508, 24,679 and 42,285 cells were scored in
      the control, unexplained infertility and severe male factor groups of patients
      respectively. In all the patients in the ISH efficiency result was approximately
      98%. In controls, unexplained infertility and severe male factor patients, the
      frequency of morphologically normal sperm cells carrying an abnormal chromosome
      constitution (XX or YY or XY or > 2 sex chromosomes signals) was 0.86, 0.75 and
      1.35% respectively. The value of this last group of patients (severe male factor)
      was significantly higher than in the other two groups of patients (P < 0.008).
      The same findings were made using the autosomic probes. Our preliminary data
      support the possibility of an increased risk from paternal origin sex chromosome
      aneuploidies in children born after intracytoplasmic sperm injection (ICSI).
      Further investigations of the cytogenetic constitution of spermatozoa from severe
      male factor patients is warranted.

PMID- 9239729
TI  - Fluorescent in-situ hybridization and sequence-tagged sites for delineation of an
      X:Y translocation in a patient with secondary amenorrhoea.
AB  - We describe a phenotypically normal female with secondary amenorrhoea due to a
      translocation of genetic material involving the long arm of chromosome X (Xq28)
      and the long arm of chromosome Y (Yq11). We used fluorescent in situ
      hybridization to localize the breakpoint on the Xq. The Y chromosome breakpoint
      was identified using polymerase chain reaction (PCR) detection of sequence-tagged
      sites (STS) specific for interval 5 at Yq11.21. The relationship between this X:Y
      translocation and premature ovarian failure is discussed.

PMID- 9239730
TI  - Direct assessment of triploid cells in mosaic human fetuses by fluorescence in
      situ hybridization.
AB  - Villous tissues from 30 spontaneous abortions and the same number of artificial
      abortions were obtained and analysed for the frequency of polyploid cells. Single
      cell suspensions were made from these tissues without culture and the ploidy of >
      100 cells was analysed. Trisomies of chromosomes 17 and 4 have rarely been
      reported in villous cells of spontaneous abortions, suggesting that the presence
      of more than three copies of chromosomes 17 and 4 per cell indicates polyploidy.
      The number of chromosomes 17 and 4 was detected by fluorescence in-situ
      hybridization analysis using centromeric probes D17Z1 and D4Z1. Most villous
      cells from cases of spontaneous and artificial abortions had two D17Z1 or D4Z1
      signals per cell, with very small percentages of cells (0.5 +/- 0.4%) showing
      three signals per cell. However, in four cases of spontaneous abortions, 2-12% of
      cells had three D17Z1 or D4Z1 signals per cell. This indicates the presence of
      triploid cells in these cases of spontaneous abortion, at a significantly higher
      frequency compared to artificial or the remaining 26 cases of spontaneous
      abortion. In addition, three cases contained 0.2-0.4% of cells showing six
      signals, indicating that these cells were dividing triploid cells. The low
      frequency of mosaicism reported here would not be detectable by conventional
      chromosomal analysis.

PMID- 9239731
TI  - Isolation of fetal erythroid cells from maternal blood based on expression of
      erythropoietin receptors.
AB  - Fetal nucleated red cells which pass into the maternal circulation during
      pregnancy are a potential cell source for non-invasive prenatal genetic
      diagnosis. To sort these rare cells with a high degree of specificity, we
      focussed our attention on the erythropoietin receptor, a strictly erythroid
      specific antigen. We first labelled these receptors with biotin-(sialyl)
      erythropoietin, then isolated the erythroid cells by magnetic beads conjugated
      with streptavidin in a MiniMACS (magnetic cell separator). The effectiveness of
      this strategy for the enrichment of fetal cells was evaluated by assessing its
      accuracy for gender prediction in 18 male-bearing pregnancies. Polymerase chain
      reaction (PCR) results on maternal blood samples sorted for Epo-r and CD71
      antigens displayed similar sensitivity (55% Epo-r, 61% CD71) in detecting Y
      specific sequences while immunocytochemical studies on four maternal blood
      samples, sorted after increasing the binding time of the ligand to Epo-r (8 h),
      showed a substantial improvement in fetal cell recovery and purity. We conclude
      that sorting by Epo-r/biotin-(sialyl)-erythropoietin provides effective
      enrichment of fetal nucleated red cells allowing the possibility of direct
      prenatal cytogenetic analysis by multiprobe fluorescent in-situ hybridization
      (FISH).

PMID- 9239732
TI  - Use of amiloride to reduce osmotic stress injury of mouse oocytes during
      cryopreservation.

PMID- 9239733
TI  - Relaxin-like factor: a highly specific and constitutive new marker for Leydig
      cells in the human testis.
AB  - The complete protein-coding region of the human relaxin-like factor (RLF;
      formerly Ley-I-L) was cloned by reverse transcription-polymerase chain reaction
      from human testis and subcloned into a bacterial expression plasmid for the
      production of recombinant human RLF in Escherichia coli. Polyclonal antibodies
      were raised against the recombinant RLF, as well as against a peptide epitope
      from the B-domain of the RLF polypeptide. Antibodies were used for
      immunohistochemistry of Bouin-fixed, paraffin-embedded samples of human testis
      tissues. Specific immunoreactivity was located exclusively in the Leydig cells
      with a consistent high intensity of staining, showing similar spatial
      distribution to other Leydig cell markers, such as the luteinizing hormone (LH)
      receptor and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and to the pattern
      of RLF mRNA shown by in-situ transcript hybridization. In biopsy samples from
      patients with severe disturbances of spermatogenesis, RLF staining intensity was
      consistently high in all cases, unlike staining for 3 beta-HSD which varied
      considerably between patients. Immunostaining for RLF would thus appear to offer
      an interesting new marker for Leydig cells in human testis samples.

PMID- 9239734
TI  - The expression of leptin and its receptors in pre-ovulatory human follicles.
AB  - The expression of leptin and its receptors was examined by reverse transcriptase
      polymerase chain reaction and immunofluorescence in granulosa and cumulus cells
      of pre-ovulatory follicles and in meiotically mature oocytes obtained from women
      undergoing in-vitro fertilization. Leptin concentrations were measured in newly
      aspirated follicular fluids and in maternal serum before and after the
      administration of an ovulatory dose of human chorionic gonadotrophin. The
      findings demonstrate leptin expression at the mRNA and protein levels by
      granulosa and cumulus cells, and the presence of leptin in mature human oocytes.
      While an association between follicular leptin concentration and embryo
      development was not observed, a post-ovulatory increase in serum leptin
      concentration was associated with implantation potential. The results are
      discussed with respect to possible roles of leptin in early human development.

PMID- 9239735
TI  - RNA in spermatozoa: implications for the alternative haploid genome.
AB  - The presence of specific messenger RNAs in the nuclei of mature mammalian
      spermatozoa has been demonstrated by several independent laboratories. Others
      have suggested that various polymerases may also be active in mature spermatozoa.
      This has led to the notion that the 'sleeping' genome may not be so quiescent
      after all. The alternate use of somatic-like nucleosomal and haploid protamine
      packaging structures to assemble sperm chromatin and the ordered array of
      chromosomes within the mature human sperm nucleus support this view. This had led
      us to address the issue of whether a somatic-like organization of select regions
      of the paternal genome and the mRNAs present in spermatozoa were correlated.
      Results from this and other laboratories suggest that this in indeed the case.
      Potential roles for this novel packaging and the accumulation of transcripts
      within the mature human nucleus are discussed.

PMID- 9239737
TI  - Inducible nitric oxide synthase is present in the rat placenta at the fetal
      maternal interface and decreases prior to labour.
AB  - The aim of this study was to investigate the expression and distribution patterns
      of the inducible isoform of nitric oxide synthase (iNOS) in rat placenta during
      gestation and term labour. The expression of iNOS isoform was assessed by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting
      with monoclonal antibodies. Two specific bands were detected corresponding to 135
      and 124 kDa in all placenta samples. The upper band (135 kDa) was identified as
      iNOS due to its correspondence with the band obtained with mouse macrophages
      (positive control). Compared with its concentrations on day 16, iNOS decreased
      steadily toward the end of gestation to approximately 37% on day 20, 20% on day
      22 before labour and 12% during labour (p < 0.01). The lower band (124 kDa)
      drastically increased (to almost double) from day 16 to day 18 but returned to
      initial values on day 22, during delivery. Immunohistochemical staining of
      placentae at day 16 and 22 using rabbit polyclonal anti-iNOS antibody revealed
      labelling specifically concentrated in the trophospongial cell layer, at the
      fetal-maternal interface. The most conspicuous iNOS staining was associated with
      islands of cells referred to as vacuolated 'glycogen cells'. Staining was greatly
      decreased during labour. The changes in placental iNOS expression suggest a
      'paracrine' role for NO in regulating uterine contractility, blood flow and
      immunosuppression required for pregnancy maintenance. NO withdrawal at term may
      also be involved in the initiation of labour.

PMID- 9239736
TI  - cynDAZLA: a cynomolgus monkey homologue of the human autosomal DAZ gene.
AB  - A gene on the human Y chromosome, specifically deleted in azoospermic patients
      (DAZ: deleted in azoospermia), and a DAZ homologue (DAZH) on human chromosome 3,
      have been recently described. In the present work we report the isolation and
      characterization of the corresponding DAZH gene of the cynomolgus monkey (Macaca
      fascicularis), which we have named cynDAZLA (cynomolgus DAZ-like autosomal).
      Reverse transcription-polymerase chain reaction was used to amplify the monkey
      DAZ homologue, and sequence analysis revealed an open reading frame of 888 bp
      encoding 295 amino acids. Northern blot hybridization of different tissues to a
      probe derived from the cynDAZLA cDNA detected a transcript of 3.5 kb that, in the
      male, was expressed only in the testis. Comparison of the cynDAZLA sequence to
      autosomal DAZ homologues from human, mouse and Drosophila showed two RNA
      recognition motifs (RRM) and the presence of only one DAZ consensus repeat
      compared with the seven repeats found in the human DAZ gene on the Y chromosome.
      The homology of the cynDAZLA cDNA compared with the human DAZH and mouse dazla
      cDNAs is 97.97 and 87.46% respectively. The identification of the monkey cynDAZLA
      enables further studies regarding the putative functions of DAZH, such as onset
      of expression and hormonal dependence of this gene.

PMID- 9239738
TI  - Differential expression of type II, IV and cytosolic PLA2 messenger RNA in human
      intrauterine tissues at term.
AB  - The involvement of phospholipase A2 (PLA2) enzymes in the formation of
      biologically-active phospholipid metabolites by human gestational tissues has
      principally been characterized by the use of enzyme activity assays. While such
      assays have established the presence of functional PLA2 activity, there is a
      paucity of information concerning the tissue distribution and relative
      contribution to net activity made by specific PLA2 isozymes. In particular, both
      secretory and cytosolic isozymes may be involved in gestational tissue
      phospholipid metabolism. Thus, the aim of this study was to test the hypothesis
      that phospholipase A2 mRNA transcripts encoding Type II, Type IV and cytosolic
      PLA2 are tissue-specifically expressed in human amnion, choriodecidua and
      placenta obtained at term. The relative expression of polyA+ mRNA encoding these
      PLA2 isozymes was determined by Northern blot analysis and laser densitometry.
      The data obtained confirm the tissue-specific expression of PLA2 mRNA in human
      intrauterine tissues. Cytosolic PLA2 mRNA was most abundantly expressed in amnion
      when compared to either choriodecidua (which was 5-fold less than amnion; P <
      0.001) or placenta (72-fold less than amnion; P < 0.001). In contrast, the
      secretory PLA2 mRNA transcripts (i.e. Type II and Type IV) were most abundantly
      expressed in placenta. Type II PLA2 mRNA expression in choriodecidua and amnion
      was 30-fold less than that observed in placenta (both P < 0.001). Type IV PLA2
      mRNA expression was 37-fold (P < 0.001) and 73-fold (P < 0.001) less in
      choriodecidua and amnion respectively. These data support the conclusion that
      cytosolic PLA2 is the principal PLA2 isozyme mediating phospholipid metabolism
      and the liberation of fatty acid substrate (i.e. arachidonic acid) in term
      amnion, while secretory PLA2 isozymes, and in particular, Type II PLA2 play a
      major role in phospholipid metabolism in term placenta.

PMID- 9239740
TI  - Characterization and isolation of SOB2, a human sperm protein with a potential
      role in oocyte membrane binding.
AB  - G12 monoclonal antibody (mAb), one of a library of constructed mAb directed
      against human sperm proteins, was found by immunoperoxidase staining to label the
      post-acrosomal and neck regions of fixed human cauda epididymal and ejaculated
      spermatozoa. Epithelium and fluid of caput epididymis were strongly labelled
      while there was no staining on testis and efferent ducts. Western lot analysis
      revealed that G12 antibody reacted with proteins of 17.5, 18 and 19 kDa in human
      spermatozoa. This pattern seems to be specific for mature human spermatozoa, as
      it has not been observed either in other human tissues tested, or in spermatozoa
      from different animals. SOB2, the corresponding protein, was isolated from NP40
      extracted human spermatozoa by using preparative electrophoresis, followed by
      isoelectrofocusing according to its isoelectric point of 6.4 G12 Fab fragments
      strongly inhibited binding of human spermatozoa to zona-free hamster oocytes (up
      to 86% inhibition at 200 micrograms/ml). Impairment of binding was dependent on
      the concentration of purified G12 immunoglobulin (Ig)G1, and significant even at
      10 micrograms/ml. There was no inhibitory effect of G12 antibody on sperm
      motility parameters or triggering of the acrosome reaction and it did not inhibit
      binding to human zona pellucida. These results indicate that SOB2 is likely to
      participate in membrane oocyte binding, and my be potential candidate for the
      development of a contraceptive vaccine.

PMID- 9239739
TI  - Expression of glycans linked to natural killer cell inhibition on the human zona
      pellucida.
AB  - Protection of the gametes from potential immune responses is a primary function
      in human reproduction. The primary cell type responsible for the innate immune
      response in the uterus is the natural killer (NK) cell. NK cells normally
      recognize Class I major histocompatibility (MHC) molecules on potential target
      cells. Since both human spermatozoa and human oocytes do not express Class I MHC
      molecules on their surfaces, the appropriate cell surface signal that abrogates
      potential NK cell-mediated responses directed against these gametes is unknown.
      Recent evidence indicates that surface expression of bisecting-type N-linked
      glycans protects cells sensitive to NK cell-mediated lysis. We report that the
      zona pellucida of the human egg and plasma membranes of human spermatozoa
      potentially bind a lectin probe specific for bisecting type glycans in a
      carbohydrate-dependent manner. Since the innate immune response in the uterus is
      primarily mediated by NK cells, our results indicate that human gametes may be
      protected from this response by expressing bisecting type N-linked glycans on
      their surfaces.

PMID- 9239741
TI  - Analysis of chorionic gonadotrophin secreted by cultured human blastocysts.
AB  - Embryos produced in an in-vitro fertilization (IVF) programme, but which were
      unsuitable for transfer to patients because they originated from one (1PN) or
      three pronuclear (3PN) oocytes or because they originated from two pronuclear
      (2PN) oocytes but cleaved normally, were maintained in tissue culture. The
      embryos that progressed to blastocytes were cultured to day 14 of development in
      order to study their daily output of human chorionic gonadotrophin (HCG).
      Blastocysts that released large amounts of immunoreactive HCG, which continued to
      increase daily during the study period, provided the culture supernatants used in
      the present studies. The heterogeneity of HCG released by blastocyst tissues on
      days 11 and 14 of development was studied by a chromatofocusing method which
      separates the isoforms of the gonadotrophin based on differences in their
      isoelectric points. It was found that the secreted HCG was composed of several
      molecular forms and that this heterogeneity changed from day 11 to 14 of
      development. The early blastocyst tissues produced more acidic HCG isoforms than
      the more advanced embryonic tissues. Differences in the apparent ploidy of the
      blastocyst tissues studied did not affect significantly the distribution of the
      HCG isoforms secreted either on day 11 or day 14 of development. These results
      suggest that the bioactivity of the HCG secreted by blastocytes may change with
      time and with differentiation of the trophectoderm. In addition, the results
      suggest that the ploidy of early blastocytes does not influence the nature of the
      HCG secreted.

PMID- 9239742
TI  - Prenatal diagnosis of the thalassaemia syndromes by rapid DNA analytical methods.
AB  - Prenatal diagnostic strategies applied today are based mainly on polymerase chain
      reaction (PCR) analytical protocols. In Greece a wide range of mutations underlie
      the thalassaemic haemoglobinopathies, and consequently a variety of PCR-based
      methods are required to facilitate diagnosis of all potential abnormal genotypes.
      PCR protocols include those which are relatively simple and others that are
      technically challenging, but very few have been designed for high through-put
      clinical diagnostics. Over a period of 18 months we carried out prenatal
      diagnosis of 147 pregnancies (150 fetal samples) at risk for a wide range of
      haemoglobinopathies. This involved the precise characterization of parental
      genotypes and the subsequent analysis of fetal DNA samples. In this series, 18
      different mutations in the alpha- or beta-globin clusters were identified. For
      the characterization of these mutations, five PCR-based protocols were selected:
      denaturing gradient gel electrophoresis (DGGE), amplification refractory mutation
      system (ARMS) PCR, restriction endonuclease analysis of PCR fragments,
      oligonucleotide hybridization and 'gap' PCR for detection of deletions. To avoid
      spurious diagnosis due to contamination of fetal samples, two additional methods
      were used to genotype polymorphic variable nucleotide tandem repeat (VNTR)
      regions of the genome in parental and fetal samples. Through analysis of the
      results we assess the advantages and drawbacks of the selected PCR-based
      protocols for providing routine clinical diagnostics.

PMID- 9239743
TI  - Transgenic analysis of prion diseases.
AB  - Prion diseases are fatal transmissible neurological disorders afflicting a range
      of mammalian species. Although still controversial, a large body of data suggests
      that the causative agent may be composed entirely of a small glycoprotein. The
      brains of infected animals have accumulations of a pathogenic protease-resistant
      isoform (PrPsc) of a normal host-encoded glycoprotein, PrPc or prion protein. A
      number of lines of biochemical evidence implicate the disease-specific isoform,
      PrPsc, as the transmissible agent and genetic analysis has shown tight linkage
      between PrP gene mutations and polymorphisms and differential susceptibility to
      prion diseases, Perhaps the strongest evidence for a protein-only model of the
      agent is that PrP gene-ablated mice are resistant to scrapie and that mice with
      PrP mutation, corresponding to those found in a human familial prion disease,
      spontaneously develop a transmissible prion disease. This review describes the
      critical role that transgenic technology has played in the study of the biology
      of prion diseases and considers the issues raised by this work.

PMID- 9239744
TI  - X spermatozoa larger than Y in 1973.

PMID- 9239745
TI  - Neurochemistry with microscopes: homage to Annica Dahlstrom.

PMID- 9239746
TI  - Noradrenaline storing vesicles in sympathetic neurons and their role in
      neurotransmitter release: an historical overview of controversial issues.
AB  - More than 25 years have passed since the original demonstration that proteins
      such as chromogranin A and dopamine-beta-hydroxylase, which are co-stored
      together with noradrenaline in large dense cored vesicles in adrenergic nerves,
      are released by exocytosis. Despite much evidence in favour, it was for a long
      time thought that large dense cored vesicles were not eminently involved in the
      release of noradrenaline. The present review attempts to demonstrate, making use
      of evidence from different approaches, that the release of noradrenaline from
      sympathetic neurons occurs ultimately from large dense cored vesicles. A model of
      the secretory cycle is proposed.

PMID- 9239748
TI  - ATP-dependent formation of free synaptic vesicles from PC12 membranes in vitro.
AB  - Synaptic vesicles are released from membranes during incubation at 37 degrees C
      in the presence of ATP (adenosine triphosphate). The donor membranes are a
      rapidly sedimenting fraction derived from the neuroendocrine cell line PC12
      (pheochromocytoma 12). These starting membranes contain the synaptic vesicle
      proteins, synaptophysin and SV2, and the endosomal markers transferrin receptor
      and cation-independent MPR (mannose 6-phosphate receptor). Incubating the
      membranes in vitro increased the amount of organelles that migrate as synaptic
      vesicles in velocity sedimentation gradients. The synaptic vesicle fractions that
      contain both synaptophysin and SV2 do not contain endosomal markers. A synaptic
      vesicle increase in vitro is time-, cytosol-, ATP- and temperature-dependent and
      is inhibited by NEM (N-ethylmaleimide), BFA (brefeldin A) and aluminum fluoride,
      but not GTP gamma S (guanosine-5'O-C3-thiotriphosphate). The production of
      synaptic vesicles under these conditions is unlike the de novo generation of
      vesicles from endosomes (1). Incubation in vitro under the conditions described
      here may allow the final stages of synaptic vesicle formation, uncoating or
      undocking, to occur but not the initiation of formation de novo.

PMID- 9239749
TI  - Immunocytochemical localization of synaptic proteins at vesicular organelles in
      PC12 cells.
AB  - The distribution of the three synaptic vesicle proteins SV2, synaptophysin and
      synaptotagmin, and of SNAP-25, a component of the docking and fusion complex, was
      investigated in PC12 cells by immunocytochemistry. Colloidal gold particle-bound
      secondary antibodies and a preembedding protocol were applied. Granules were
      labeled for SV2 and synaptotagmin but not for synaptophysin. Electron-lucent
      vesicles were labeled most intensively for synaptophysin but also for SV2 and to
      a lesser extent for synaptotagmin. The t-SNARE SNAP-25 was found at the plasma
      membrane but also at the surface of granules. Labeling of Golgi vesicles was
      observed for all antigens investigated. Also components of the endosomal pathway
      such as multivesicular bodies and multilamellar bodies were occasionally marked.
      The results suggest that the three membrane-integral synaptic vesicle proteins
      can have a differential distribution between electron-lucent vesicles (of which
      PC12 cells may possess more than one type) and granules. The membrane compartment
      of granules appears not to be an immediate precursor of that of electron-lucent
      vesicles.

PMID- 9239747
TI  - Membrane composition of adrenergic large and small dense cored vesicles and of
      synaptic vesicles: consequences for their biogenesis.
AB  - The membrane proteins of adrenergic large dense cored vesicles, in particular
      those of chromaffin granules, have been characterized in detail. With the
      exception of the nucleotide carrier all major peptides have been cloned. There
      has been a controversy whether these vesicles contain antigens like
      synaptophysin, synaptotagmin and VAMP or synaptobrevin found in high
      concentration in synaptic vesicles. One can now conclude that large dense core
      vesicles also contain these peptides although in lower concentrations. The
      biosynthesis of large dense core vesicles is analogous to that of other peptide
      secreting vesicles of the regulated pathway. One cannot yet definitely define the
      biosynthesis of small dense core vesicles which apparently have a very similar
      membrane composition to that of large dense core vesicles. They may form directly
      from large dense core vesicles when their membranes have been retrieved after
      exocytosis. These membranes may become sorted in an endosomal compartment where
      peptides may be deleted or added. Such an addition could be derived from
      synaptophysin-rich vesicles present in adrenergic axons. However small dense core
      vesicle peptides may also be transported axonally independent of large dense core
      vesicles. For proving one of these possibilities some crucial experiments have
      been suggested.

PMID- 9239750
TI  - The role of axonal cytoskeleton in diabetic neuropathy.
AB  - The neuropathy associated with diabetes includes well documented impairment of
      axonal transport, a reduction in axon calibre and a reduced capacity for nerve
      regeneration. All of those aspects of nerve function rely on the integrity of the
      axonal cytoskeleton. Alterations in the axonal cytoskeleton in experimental
      diabetes include an insulin-dependent non-enzymatic glycation of actin that is
      reflected in increased glycation of platelet actin in the clinical situation.
      There is a reduced synthesis of mRNA for the isoforms of tubulin that are
      associated with nerve growth and regeneration and an elevated non-enzymatic
      glycation of peripheral nerve tubulin in both diabetic patients and diabetic
      animals. mRNAs for neurofilament proteins are selectively reduced in the diabetic
      rat and post-translational modification of at least one of the neurofilament
      proteins is altered. There is some evidence that altered expression of isoforms
      of protein kinases may contribute to these changes.

PMID- 9239752
TI  - Effect of subtype-specific Ca(2+)-antagonists and Ca(2+)-free media on the field
      stimulation-evoked release of ATP and [3H]acetylcholine from rat habenula slices.
AB  - The involvement of different subtypes of voltage-sensitive (Ca2+ channels in the
      initiation of field stimulation-induced endogenous adenosine triphosphate (ATP)
      and [3H]acetylcholine ([3H]ACh) release was investigated in the superfused rat
      habenula slices. ATP, measured by the luciferin-luciferase assay, and [3H]ACH
      were released simultaneously from the tissue in response to low frequency
      electrical stimulation (2 Hz, 2.5 msec, 360 shocks). The N-type Ca(2+)-channel
      blocker omega-conotoxin GVIA (omega-CgTX, 0.01-1 microM) reduced the stimulation
      evoked release of ATP and [3H]ACh in a dose-dependent manner. Similarly, the P
      type Ca2+ channel antagonist omega-agatoxin IVA (omega-Aga IVA) (0.05 microM) and
      the inorganic Ca(2+)-channel blocker Ca2+ (0.2 mM) inhibited the outflow of both
      transmitters, while Ni2+ (0.1 mM) was without significant effect. A high
      correlation was observed between the percent inhibition of ATP release and
      percent inhibition of ACh release caused by the different Ca2+ antagonists. Long
      term perfusion (i.e., 90 min) with Ca(2+)-free solution inhibited the evoked
      release of ATP and [3H]ACh. In contrast, perfusion of slices with the same media
      for a shorter time (i.e., 20 min) did not reduce the release of [3H]ACh and ATP
      but even increased the evoked-release of ATP about fourfold. The breakdown of
      extracellular ATP was not blocked under low [Ca2+]0 condition, measured by the
      creatine phosphokinase assay and HPLC-UV technique. Application of extra- or
      intracellular Ca2+ chelators, and dipyridamole (2 microM), the nucleoside
      transporter inhibitor, did not reduce the excess release of ATP after short-term
      perfusion with Ca(2+)-free media. Tetrodotoxin (TTX, 1 microM), while inhibiting
      the majority of ATP release under normal conditions, was also unable to reduce
      release under low [Ca2+]0 conditions. In summary, we showed that both N- and P
      type Ca2+ channels are involved in the initiation of electrical stimulation
      evoked release of ATP and [3H]ACh in the rat habenula under normal extracellular
      calcium concentration. Under low [CA2+]0 conditions an additional release of ATP
      occurs, which is not associated with action potential propagation.

PMID- 9239753
TI  - Secretory patterns of tryptophan metabolites in midgut carcinoid tumor cells.
AB  - Hormonal overproduction is a significant problem in patients with disseminated
      midgut carcinoid tumors. Serotonin (5-HT) is one major product secreted from such
      tumors and the urinary excretion of its metabolite (5-hydroxyindoleacetic acid, 5
      HIAA) serves as an important tumor marker. The present study aimed at elucidating
      mechanisms of tryptophan metabolite secretion to facilitate the treatment of the
      carcinoid syndrome. When midgut carcinoid tumors were studied in primary cell
      cultures, several similarities with adrenergic neurons could be demonstrated. A
      marked dose-dependent depletion of intracellular 5-HT could be induced by
      reserpine, and monoamine oxidase-activity was revealed both in functional studies
      and by immunocytochemistry. Differences between tumors in the ratios of
      tryptophan metabolites released indicated that enzymes for synthesis and
      degradation of 5-HT were individually expressed. Treatment with the somatostatin
      analogue octreotide or with dexamethasone decreased the extracellular levels of
      tryptophan metabolites, but the mechanisms were partly different. In some tumors
      octreotide also decreased the synthesis of 5-HT, while dexamethasone markedly
      increased the intracellular 5-HIAA levels. It is of clinical interest to further
      elucidate these mechanisms, since the two drugs may have complementary actions in
      carotid crisis reactions.

PMID- 9239751
TI  - Basal forebrain cholinergic immunolesion by 192IgG-saporin: evidence for a
      presynaptic location of subpopulations of alpha 2- and beta-adrenergic as well as
      5-HT2A receptors on cortical cholinergic terminals.
AB  - To study whether the changes in cortical noradrenergic and serotonergic
      mechanisms observed in patients with Alzheimer's disease are the consequence of
      reduced cortical cholinergic activity, a novel colinergic immunotoxin (conjugate
      of the monoclonal antibody 192IgG against the lower affinity nerve growth factor
      receptor with the cytotoxic protein saporin, 192IgG-saporin) was used to produce
      a specific and selective loss of cholinergic cells in rat basal forebrain nuclei.
      To correlate the responses to cholinergic immunolesion in cholinoceptive cortical
      target regions with cholinergic hypoactivity, quantitative receptor
      autoradiography to measure adrenoceptors and 5-hydroxytryptamine (5-HT) receptor
      subtypes, and histochemistry to estimate acetylcholinesterase activity, were
      performed in adjacent brain sections. alpha 1-adrenoceptor and 5-HT1A receptor
      binding were not affected by cholinergic immunolesion in any of the cortical and
      hippocampal regions studied. However, cholinergic immunolesion resulted in
      significantly reduced alpha 2- and beta-adrenoceptor as well as 5-HT2A receptor
      binding in a number of cortical and hippocampal regions displaying a reduced
      activity of acetylcholinesterase, already detectable seven days after a single
      injection of 192IgG-saporin and persisting up to three months post lesion without
      any significant recovery. The data suggest that at least a subpopulation of alpha
      2- and beta-adrenoceptor as well 5-HT2A receptor subtype is present on cortical
      and hippocampal cholinergic terminals originating in the basal forebrain. The
      lesion-induced receptor changes suggest that the alterations in cortical 5-HT2
      receptor binding observed in patients with Alzheimer's disease might be secondary
      to cholinergic deficits.

PMID- 9239754
TI  - Constitutive expression of calmodulin-binding phosphoprotein GAP-43 in rat
      serotonergic and noradrenergic cell groups which project to the spinal cord.
AB  - In situ hybridization was combined with serotonin (5-hydroxytryptamine, 5-HT) or
      tyrosine hydroxylase immunocytochemistry and with Fluoro-Gold retrograde labeling
      of bulbo-spinal pathways in order to investigate the expression of GAP-43 mRNA in
      monoamine cell groups of the adult rat brain stem. Consistent with previous
      reports, GAP-43 mRNA was observed in serotonin and dopamine cell groups in the
      pons. In addition, GAP-43 expressing cells were observed in all the major
      monoamine cell groups in the medulla. Thus the B1, B2 and B3 serotonin cell
      groups all showed high GAP-43 expression in all contained many GAP-43 expressing
      serotonin cells with spinal cord projections. The A1, A2, A5 and A6 noradrenaline
      cell groups also showed high GAP-43 expression, although cells with spinal cord
      projections were largely restricted to the A5 group and A6 subcoeruleus region.
      In all areas, GAP-43 expressing cells with spinal cord projections were also
      observed which were not serotonergic or noradrenergic.

PMID- 9239755
TI  - Chronic blockade of nitric oxide synthesis elevates plasma levels of
      catecholamines and their metabolites at rest and during stress in rats.
AB  - Formation of nitric oxide, and endothelium-derived relaxing factor, can be
      inhibited by administration of N-nitro-L-arginine methylesther (L-NAME). In the
      present study, the activity of the sympathoadrenal system in rats with blood
      pressure (BP) elevation induced by L-NAME was investigated. L-NAME was
      administered in a dose of 50 mg/kg, i.p. every 12 h for 4 days. Blood samples
      were collected via chronically inserted arterial catheters in conscious, freely
      moving rats at rest and during immobilization stress. Plasma epinephrine (EPI),
      norepinephrine (NE), and dopamine (DA), as well as catecholamine metabolites
      dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were measured
      by HPLC method. In L-NAME treated animals, which slowed a significant increase in
      BP, plasma EPI levels were markedly elevated both before and during stress.
      Plasma NE levels were not significantly increased, however, DHPG levels, which
      indicate NE turnover and reuptake, were highly elevated. Plasma DA levels were
      not changed after L-NAME administration but DA metabolite DOPAC showed a
      significant elevation both under basal conditions and during stress. Thus, the
      present results indicate that the prolonged blockade of nitric oxide synthesis
      that causes arterial hypertension is associated with an activation of the
      sympathoadrenal system.

PMID- 9239756
TI  - Responses of mature and aged sympathetic neurons to laminin and NGF: an in vitro
      study.
AB  - Whilst the potent effects of NGF and laminin on developing neurons are well
      documented, relatively little is known about the effects of, or altered
      availability of or altered responsiveness to, these substances on the growth of
      adult neurons. We have therefore examined this question using explant cultures of
      sympathetic neurons from the superior cervical ganglion (SCG) of mature and aged
      rats. Explants were grown on substrata containing different doses of laminin,
      either with or without added NGF in culture medium containing FCS. Individually,
      laminin and NGF had relatively small effects on neurite outgrowth and length,
      which tended to be reduced in old neurons. In contrast, laminin in the presence
      of exogenous NGF exerted a powerful effect on nerve growth which was
      substantially greater than the sum of the effects of the individual factors. This
      synergy was evident in all experimental groups and was greatest in old explants
      at high doses of laminin, where growth was comparable to that of mature neurons.
      The dose-response curve of old neurons to laminin in the presence of added NGF
      indicated reduced responsiveness. These results suggest that variations in the
      availability of laminin and/or exogenous NGF, together with altered patterns of
      neuronal responsiveness, may contribute to impaired neuronal plasticity in old
      age.

PMID- 9239757
TI  - Distribution of peptide-containing neurons in the developing rat right atrium,
      studied using immunofluorescence and confocal laser scanning.
AB  - The developmental pattern and distribution of peptide-containing neurons in the
      rat heart right atrium has been studied by indirect immunofluorescence.
      Antibodies against neuropeptide Y (NPY), substance P (SP), and vasoactive
      intestinal polypeptide (VIP) were applied to whole-mount stretch preparations of
      the right atria from hearts of newborn to 40 day-old animals. NPY-like
      immunoreactivity (L1) was compared with the synaptic vesicle marker SV2 in double
      immunoincubation studies. The distribution of immunofluorescence was studied by
      confocal laser scanning microscopy. NPY-L1 and SP-L1 were present throughout the
      atria already at birth, in contrast to VIP-L1 that was observed at day 10. The
      postnatal changes of innervation were basically quantitative, with an increase in
      density of nerve fibres and number of varicosities, while the basic pattern of
      innervation was essentially established during the first 1-10 days. NPY- and SP
      positive bundles of fibres appeared to enter the right atrium along the superior
      caval vein, having extrinsic origins. Nerve fibres with NPY-L1 colocalized in
      most nerve terminals with SV2-L1, and showed a developmental pattern similar to
      that observed for adrenergic neurons earlier. These NPY/SV2 positive fibres
      probably represent the extrinsic NPY innervation. In addition, NPY-L1 was
      identified in large intrinsic nerve cells bodies located near the
      atrioventricular (AV) region. Most of the VIP-L1 was observed in short nerve
      fibres originating in intrinsic VIP-positive cell bodies, but a few apparently
      extrinsic VIP-positive fibres were found, probably representing preganglionic
      parasympathetic neurons. SP in the atria was probably of extrinsic (sensory)
      origin and no nerve cell bodies with SP-L1 were detected. The results show that
      the peptidergic innervation in the developing rat right atrium involves both
      extrinsic and intrinsic peptidergic neurons which may participate in the
      regulation of neurotransmission in local neuronal circuits.

PMID- 9239758
TI  - Modes of peptide binding in G protein-coupled receptors.
AB  - The G-protein coupled seven transmembrane domain receptors bind a wide variety of
      ligands of different molecular size ranging from small monoamines to large
      neuropeptides and peptide hormones. This review summarises data from studies on
      the localisation of the binding site for a few neuropeptides in their receptors
      and compares this to the binding pockets for non peptide ligands. The main
      conclusion is that neuropeptide binding involves residues on the top of several
      transmembrane domains and in extracellular loops of the receptors while the non
      peptide type ligands to the same receptors tend to bind deeper in the plane of
      the membrane, between several transmembrane domains--similarly to monoamines.
      Thus the antagonism exerted by most of the non peptide type ligands is an
      allosteric phenomenon whereby binding of these to another site than the peptide
      binding site stablises a "non agonist" binding, and for signalling inactive,
      conformation of the 7 TM receptor.

PMID- 9239759
TI  - The endothelin system and endothelin-converting enzyme in the brain: molecular
      and cellular studies.
AB  - The biologically active vasoactive peptides, the endothelins (ETs), are generated
      from inactive intermediates, the big endothelins, by a unique processing event
      catalysed by the zinc metalloprotease, endothelin converting enzyme (ECE). In
      this overview we examine the actions of endothelins in the brain, and focus on
      the structure and cellular locations of ECE. The heterogeneous distribution in
      the brain of ET-1, ET-2, and ET-3 is discussed in relation to their hemodynamic,
      mitogenic and proliferative properties as well as their possible roles as
      neurotransmitters. The cellular and subcellular localization of ECE in neuronal
      and in glial cells is compared with that of other brain membrane
      metalloproteases, neutral endopeptidase-24.11 (neprilysin), angiotensin
      converting enzyme and aminopeptidase N, which all function in neuropeptide
      processing and metabolism Unlike these ectoenzymes, ECE exhibits a dual
      localisation in the cell, being present on the plasma membrane and also, in some
      instances, being concentrated in a perinuclear region. This differential
      localization may reflect distinct targeting of different ECE isoforms, ECE-1
      alpha, ECE-1 beta, and ECE-2.

PMID- 9239760
TI  - Uridine nucleotide receptors and their ligands: structural, physiological, and
      pathophysiological aspects, with special emphasis on the nervous system.
AB  - This review presents data on metabotropic uridine nucleotide receptor subtypes
      (P2UR) activated by UTP, sometimes also by UDP and/or ATP. Some chemical details
      of receptor subtypes and ligand interactions are described. Ligand-activated P2UR
      subtypes may couple to different second messengers, yet little is known about the
      nature of the coupling G-proteins. Data evaluating UTP as a physiological ligand
      include UTP origin, release and metabolism and illuminate especially roles for
      P2UR in the nervous system. No evidence shows UTP as a synaptic transmitter;
      sympathetic neurons may, however, carry P2UR allowing UTP-stimulation of
      norepinephrine release. UTP and derivatives act as therapeutic agents in several
      diseases involving mutated genes of transepithelial conductance regulators,
      including cystic fibrosis. This focuses interest to the synthesis of new
      compounds. Further, therapeutically used pyrimidine and pyrimidine analogues are
      suspected to have CNS-pathological effects. The presently scarce information in
      these areas strongly underlines the need for and importance of intense research
      on the suspected pyrimidine derivative triggered pathology as well as on the role
      of P2UR receptors in physiology and pathophysiology.

PMID- 9239761
TI  - GABA-dopamine receptor-receptor interactions in neostriatal membranes of the rat.
AB  - Recent evidence has shown in membrane preparations that the binding of one ligand
      to its receptor is able to modify the binding parameters of a second receptor
      (receptor-receptor interactions), allowing the modulation of incoming signals
      onto a neuron. To further understand the gamma-amino-butyric acid (GABA)-dopamine
      (DA) interactions in the neostriatum we have carried out experiments to explore
      whether an activation of the GABA(A) receptor could affect the binding
      characteristics of the D2 DA receptor in membrane preparations of the rat
      neostriatum. The results show the GABA (30-100 nM) significantly increases the
      dissociation constant of the high affinity (KH) D2 DA binding site (labelled with
      the selective D2 DA receptor antagonist [3H]raclopride and that such an effect is
      fully counteracted by the GABA(A) receptor antagonist bicuculline (1 microM). It
      is suggested that such putative GABA(A)/D2 receptor-receptor interactions may
      take place in the somato-dendritic membrane of the striato-pallidal GABA neurons
      and that it may modulate the inhibitory effects of DA on these neurons, mediated
      via D2 receptors.

PMID- 9239762
TI  - Autoradiographic characterisation of [35S]GTP gamma S binding sites in rat brain.
AB  - The binding of [35S]GTP gamma S was characterised with autoradiography in rat
      brain. The binding was saturable, but the rate of dissociation was very slow.
      Analysis of binding isotherms revealed one class of binding sites with a Kd of
      0.8 microM. The specific binding was 98%. Different guanine nucleotides were all
      able to compete with [35S]GTP gamma S binding. However, no displacement was seen
      by the ATP-analogue App[NH]p, indicating that [35S]GTP gamma S does not bind to
      ATP-sites. Autoradiograms showed a highly homogenous distribution of [35S]GTP
      gamma S binding, in grey as well as in white matter. However, the pattern changed
      dramatically in the presence of GTP, which, unlike the non-hydrolysable GTP
      analogues Gpp[NH]p and GTP gamma S, did not displace [35S]GTP gamma S binding
      throughout the brain. In white matter areas the binding was potently displaced,
      while in many grey matter areas, e.g., the striatum, the binding was seen to
      increase. This GTP-induced increase in [35S]GTP gamma S binding was strongly
      Mg(2+)-dependent, with an optimum at 10 mM. This, together with the finding that
      the regional effects of GTP correspond well to previously reported distribution
      of low Km GTPase, suggest that the levels of binding of [35S]GTP gamma S in the
      presence of GTP may reflect functional G-protein activity.

PMID- 9239763
TI  - Specific involvement of central 5-HT1A receptors in the mediation of male rat
      ejaculatory behavior.
AB  - The aminotetralin 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT),
      pharmacologically characterized as a 5-HT1A receptor agonist, produces a
      pronounced decrease in ejaculation latency in the male rat. Stimulation of 5-HT
      receptors by a pharmacologically induced increase in the synaptic availability of
      5-HT has been shown to produce the opposite effect. The 8-OH-DPAT-induced
      decrease in ejaculation latency is specific for this compound, and some
      chemically related ergot derivatives. In this paper we review the evidence in
      support for stimulation of serotonergic autoreceptors of the 5-HT1A receptor
      subtype as a mechanism of action for effects by 8-OH-DPAT on male rat ejaculatory
      behavior. We also present the questions posed by the fact that quinpirole and
      lisuride both produce 8-OH-DPAT-like effects on male rat ejaculatory behavior.
      The effects by quinpirole, lisuride of 8-OH-DPAT are not sensitive to
      pretreatment with the DA D2/3 receptor antagonist raeclopride. Continued studies
      will show whether the effects of quinpirole and lisuride can be related to
      stimulation of 5-HT1A receptors, of all these compounds have as yet undefined
      common properties.

PMID- 9239765
TI  - Impact of a massive waterborne cryptosporidiosis outbreak on child care
      facilities in metropolitan Milwaukee, Wisconsin.
AB  - OBJECTIVE: We describe the impact of the 1993 waterborne cryptosporidiosis
      outbreak on metropolitan Milwaukee child care homes and centers. METHODS:
      Information on outbreak-related illness and changes in policies and practices was
      collected from directors of 117 facilities. Stool specimens from 129 diapered
      children from 11 centers were screened for Cryptosporidium. RESULTS: Most (74%)
      facility directors reported children or staff with diarrhea during the outbreak;
      however, only 4 (3.4%) facilities closed because of illness among staff or
      children. During the outbreak child care homes were less likely to exclude
      children with diarrhea than were child care centers. Among diapered children
      attending centers the Cryptosporidium prevalence was 30%; 29% of infected
      children had no history of diarrhea associated with the Milwaukee outbreak.
      CONCLUSIONS: Facilities continued to operate during the outbreak despite
      considerable illness among children and staff. The news media were effective
      means for providing public health information to child care facilities. Although
      secondary transmission undoubtedly took place in child care facilities, the
      presence of children with asymptomatic Cryptosporidium infections did not result
      in an increased risk of diarrhea in infant and toddler rooms.

PMID- 9239766
TI  - Fecal lactoferrin, fecal leukocytes and occult blood in the diagnostic approach
      to childhood invasive diarrhea.
AB  - OBJECTIVE: To compare fecal screening tests in the diagnostic approach to
      childhood invasive diarrhea. SETTING AND PATIENTS: We assessed 125 consecutive
      children with acute diarrhea for fecal lactoferrin, fecal leukocytes and occult
      blood from November, 1995, to June, 1996. RESULTS: Lactoferrin showed a greater
      overall sensitivity than fecal leukocytes or occult blood for detecting invasive
      pathogens. Combinations of lactoferrin or fecal leukocytes and of lactoferrin or
      occult blood or both yielded sensitivities and negative predictive values close
      to 100%, being superior to all other combinations. All patients with full breast
      feeding and mixed feeding had a positive lactoferrin test with a 1:50 dilution
      used as the cutoff. In controls without diarrhea being exclusively bottle-fed, 3
      of 15 (20%) still showed a positive lactoferrin result at the dilution of 1:50.
      This compared with 15 of 15 (100%) positive results among controls fully breast
      fed, 14 of 15 (93%) among controls predominantly breast-fed and 11 of 15 (73%)
      among control children predominantly bottle-fed. CONCLUSIONS: This study confirms
      the usefulness of lactoferrin testing as a negative predictor. Breast-feeding
      lowers the specificity of the test but does not alter the sensitivity. Fecal
      lactoferrin may be viewed as the screening test of choice to avoid expensive
      stool cultures in the diagnostic approach to invasive diarrhea.

PMID- 9239767
TI  - Cerebrospinal fluid leukocyte aggregation in meningitis.
AB  - OBJECTIVE: To evaluate whether the difference in aggregation of cerebrospinal
      fluid cells from patients with bacterial, viral, aseptic and partially treated
      meningitis can be used for diagnostic purposes. METHODS: Cerebrospinal fluid
      samples of 100 patients with meningitis (15 bacterial, 13 partially treated, 10
      viral and 62 aseptic) were compared on the basis of the predefined leukocyte
      aggregation score (LAS). RESULTS: Mean LAS was 56% in the bacterial meningitis
      group (range, 15 to 90%), 5.8% in the partially treated meningitis group (range,
      0 to 27%), 2% in the proven viral meningitis group (range, 0 to 5%) and 2% in the
      aseptic meningitis group (range, 0 to 15%). All patients with bacterial
      meningitis had a LAS of > 15%, whereas all those with viral or aseptic meningitis
      had a score of < 15%. Although most patients with partially treated meningitis
      had a low LAS, several had higher scores, which may indicate bacterial infection.
      There was no statistical correlation between number of cells, type of cells
      (mononuclear or polymorphonuclear) or cerebrospinal fluid protein and glucose
      concentration and degree of leukocyte aggregation for the different groups.
      CONCLUSION: Measurement of the LAS may contribute to the immediate differential
      diagnosis of bacterial or viral meningitis, especially in patients with very high
      pleocytosis, as sometimes seen in enteroviral meningitis. It may also serve as a
      guide for the likelihood of bacterial infection in cases of partially treated
      meningitis. Additional studies are needed to confirm these observations.

PMID- 9239764
TI  - Glycosphingolipids as potential diagnostic markers and/or antigens in
      neurological disorders.
AB  - Glycosphingolipids are most abundant in the nervous system within which are
      developmental, regional, structural and cellular differences regarding their
      composition. The are shedded to the cerebrospinal fluid and thus potential
      markers for pathogenic alterations in the brain, such as developmental
      abnormalities, demyelination, gliosis, neuronal cell destruction. The
      glycosphingolipids have also been found to be antigens in autoimmune processes
      involving the nervous system, in particular in peripheral neuropathies like
      Guillain Barre syndrome, multifocal motor neuropathy etc. The immune response
      might have been triggered by infectious agents with an antigen epitope which
      mimic the glycosphingolipid or by a primary nerve tissue damage leading to
      release of glycosphingolipids. There is a series of support for a clinical
      significance of cerebrospinal fluid glycosphingolipid determinations and the
      presence of anti-glycosphingolipid antibodies but this has to be further
      explored. This paper is a mini review of the state of the art and discuss
      methodological aspects and improvements that might help to explore the relevance
      of glycosphingolipids in neurological disorders.

PMID- 9239768
TI  - Erythromycin resistance of group A streptococci from throat samples is related to
      age.
AB  - BACKGROUND: Factors associated to increased antimicrobial resistance among
      bacterial pathogens have been widely discussed and need to be evaluated. In
      Finland resistance to erythromycin in group A streptococci has become an
      important problem among outpatients. The aim of this study was to investigate
      whether occurrence of erythromycin resistance among group A streptococci isolated
      from noninvasive infections correlates with the patients' age and sex. METHODS:
      Group A streptococci isolated from 10 162 patients were tested for erythromycin
      resistance in 21 regional microbiologic laboratories located throughout Finland.
      The age of every patient and the sex of 8121 (80%) patients were known. The
      statistical significance of the association between the patients' age or sex and
      the occurrence of erythromycin resistance in group A streptococci, isolated from
      throat swab samples (8568 isolates) or pus samples (1594 isolates), was measured
      by logistic regression analysis. RESULTS: When erythromycin resistance of the
      isolates was regressed with the patients' age and sex, the age of the patient was
      a clearly significant predictor for the throat isolates (beta coefficient = 
      0.0114, SD 0.0029, observed value of t test statistic = -3.89, P = 0.0001) but
      not for the pus isolates. The odds ratio for age was 0.99 with a 95% confidence
      interval of 0.98 to 0.99. Thus the expected risk of erythromycin resistance on a
      group A streptococcal throat isolate decreased with increasing age by 1% per
      year. No significant association between the patients' sex and the occurrence of
      erythromycin resistance was found. CONCLUSIONS: Significant differences may exist
      between different age groups in the frequency of antibiotic-resistant isolates
      among outpatients, perhaps caused by differences in antibiotic prescribing. Thus
      overall resistance levels do not necessarily represent all age groups, especially
      children.

PMID- 9239769
TI  - Nasopharyngeal pneumococcal colonization among Kenyan children: antibiotic
      resistance, strain types and associations with human immunodeficiency virus type
      1 infection.
AB  - OBJECTIVES: To compare pneumococcal nasopharyngeal colonization rates among HIV-1
      infected children with those of uninfected children born to seropositive mothers
      and those of seronegative controls. To determine the predominant serotypes and
      antimicrobial susceptibility among pneumococcal isolates in Kenya. METHODS:
      Nasopharyngeal pneumococcal colonization was examined in 207 children recruited
      from the Perinatal HIV-1 Transmission Study conducted in Nairobi, Kenya.
      Colonization was compared among HIV-1-infected children, uninfected children born
      to seropositive mothers and control seronegative children. Isolates were
      serotyped and tested for antibiotic susceptibility to penicillin, tetracycline,
      erythromycin, chloramphenicol, clindamycin and rifampin. RESULTS: Colonization
      was higher among HIV-1-infected and uninfected children than among controls only
      when associated with respiratory illnesses (86% of 7 and 60% of 20 vs. 29% of 31,
      P = 0.004). No differences were observed when children were asymptomatic (20% of
      35, 35% of 94 and 22% of 101). Intermediate penicillin resistance was found in
      60% of 94 isolates, 28% were resistant to tetracycline and all isolates were
      susceptible to the other antibiotics tested. Sixteen serotypes were identified,
      with 13, 15, 14, 6B and 19F comprising 73% of isolates. Serotype 13 was found in
      31% of colonized children. This serotype and 2 others isolated are not found in
      the current 23-valent polysaccharide vaccine. Overall 41% of colonized children
      harbored nonvaccine strains. CONCLUSIONS: Although nasopharyngeal pneumococcal
      colonization was high among children with respiratory illness born to HIV-1
      seropositive mothers, increased asymptomatic colonization did not explain the
      increased risk of invasive pneumococcal disease associated with HIV-1 infection.
      Intermediate penicillin resistance was common but high level penicillin and
      multiple antibiotic resistance were not seen. The prevalence of the unique
      strains circulating in this region will need to be considered in the design of
      effective pneumococcal vaccines for use in East Africa.

PMID- 9239770
TI  - Safety and immunogenicity of concurrent administration of measles-mumps-rubella
      varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen
      months old. The MMRV Study Group.
AB  - OBJECTIVE: To determine the safety and immunogenicity of concurrent
      administration of measles-mumps-rubella-varicella vaccine (MMRV) and PedvaxHIB
      (Haemophilus influenzae type b conjugate vaccine) vs. M-M-R II and PedvaxHIB
      followed by an optional dose of VARIVAX 6 weeks later. DESIGN: Healthy children,
      12 to 18 months of age, were randomly assigned to two groups to receive (1) MMRV
      and PedvaxHIB given concurrently or (2) M-M-R II and PedvaxHIB followed by an
      optional dose of VARIVAX 6 weeks later. SUBJECTS: The study group included 294
      healthy children, ages 12 to 18 months, with a negative history of measles,
      mumps, rubella and varicella. MAIN OUTCOME MEASURES: The seroconversion rate and
      magnitude of antibody responses when MMRV was given concurrently with PedvaxHIB
      compared with the antibody responses when VARIVAX was given 6 weeks after M-M-R
      II and PedvaxHIB. RESULTS: Healthy children, 12 to 18 months of age, who received
      MMRV and PedvaxHIB concurrently showed immune responses similar to those in the
      control group who received M-M-RII vaccine with PedvaxHIB followed by VARIVAX 6
      weeks later. Antibody titers for varicella were significantly lower when MMRV was
      administered than when varicella vaccine was given separately (0.712-fold
      difference, P = 0.028). No vaccine-related serious adverse reactions were
      reported, and no clinically significant differences were seen in the safety
      profiles of the two treatment groups. CONCLUSIONS: There were no statistically
      significant differences in the seroconversion rates between the two treatment
      groups for any of the antigens tested at 6 weeks and 1 year. Significantly lower
      geometric mean titers for varicella were noted in the group who received MMRV
      compared to VARIVAX given alone. Six-week seroconversion rates, persistence of
      immune responses at 1 year and the frequency of local and systemic reactions were
      comparable when MMRV was administered with PedvaxHIB compared with M-M-R II and
      PedvaxHIB followed by VARIVAX 6 weeks later.

PMID- 9239771
TI  - Immune responses of infants vaccinated with serotype 6B pneumococcal
      polysaccharide conjugated with tetanus toxoid.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of meningitis, bacteremia,
      pneumonia and otitis media. Pneumococcal polysaccharides are not immunogenic in
      infants, but improved immunogenicity of polysaccharide-protein conjugates has
      been demonstrated. Antibiotic-resistant pneumococci have increased the need for
      an effective vaccine. OBJECTIVE: To study the safety and immunogenicity of a
      pneumococcal type 6B polysaccharidetetanus toxoid conjugate (Pn6B-TT) in infants
      and to assess the function of antibodies. METHODS: Healthy infants were injected,
      Group A at 3, 4 and 6 months (n = 21) and Group B at 7 and 9 months (n = 19).
      Booster injection was given at 18 months. Antibodies were measured by enzyme
      linked immunosorbent assay and radioimmunoassay, and functional activity was
      measured by opsonization of radiolabeled pneumococci. Nasopharyngeal cultures
      were obtained. RESULTS: No significant adverse reactions were observed. Pn6B-IgG
      (enzyme-linked immunosorbent assay) increased to a geometric mean of 0.62
      microgram/ml (P = 0.367, compared with prevaccination titers) in Group A at 7
      months and 1.22 micrograms/ml (P < 0.001) in Group B at 10 months. Total Pn6B
      antibodies (radioimmunoassay) were 44 ng of antibody N/ml (P < 0.053) in Group A
      and 211 ng of antibody N/ml (P < 0.001) in Group B. A smaller increase in IgM and
      IgA anti-Pn6B was observed. Reinjection at 18 months elicited booster responses
      in total and IgG anti-Pn6B; 62% of those in Group A and 79% of those in Group B
      had > 300 ng of antibody N/ml. Opsonic activity, after initial and booster
      vaccinations, correlated with Pn6B-antibody titers. Three infants with
      nasopharyngeal cultures repeatedly positive for serogroup 6 had poor serum IgG
      responses. CONCLUSION: Our results demonstrate that Pn6B-TT is safe, elicits
      functional antibodies and memory responses in infants.

PMID- 9239772
TI  - Inactivated poliovirus vaccine alone or sequential inactivated and oral
      poliovirus vaccine in two-, four- and six-month-old infants with combination
      Haemophilus influenzae type b/hepatitis B vaccine.
AB  - BACKGROUND: Advisory committees have recommended the increased use of inactivated
      poliovirus vaccine (IPV) for children. OBJECTIVES: The purpose of this study was
      to assess the safety and immunogenicity of three schedules using IPV administered
      with diphtheria and tetanus toxoids and whole cell pertussis vaccines in a dual
      chambered syringe. Children also received a combination of Haemophilus influenzae
      type b (Hib) and hepatitis B vaccines (COMVAX). METHODS: All infants (n = 295)
      received IPV and COMVAX at 2 and 4 months of age and IPV, oral poliovirus vaccine
      (OPV) or both vaccines at 6 months and OPV at 15 months of age. RESULTS: After
      two doses of IPV 96 to 100% of infants had antibodies to poliomyelitis viruses
      types 1, 2 and 3, and after a third dose of vaccine (IPV or OPV) all but one
      child had antibodies to all three poliovirus types. After two doses of COMVAX 89
      and 96% of children had protective levels of antibody to Hib and hepatitis B,
      respectively. CONCLUSIONS: IPV is highly immunogenic in a two-dose schedule.
      Administration of a third dose of IPV or a dose of OPV at 6 months of age is
      highly effective. Simultaneous administration of a combination H. influenzae type
      b/hepatitis B vaccine did not interfere with the response to IPV.

PMID- 9239773
TI  - Shortened course of antibiotic therapy for acute otitis media, sinusitis and
      tonsillopharyngitis.

PMID- 9239775
TI  - Comparison of oral cephalexin, topical mupirocin and topical bacitracin for
      treatment of impetigo.

PMID- 9239776
TI  - Middle ear fluid concentrations of amoxicillin after large dosages in children
      with acute otitis media.

PMID- 9239774
TI  - Human intravenous immunoglobulin in primary and secondary antibody deficiencies.
AB  - IVIG is of value in patients with primary and secondary antibody deficiencies.
      High dose IVIG therapy is usually the treatment of choice for patients with
      primary antibody deficiency disease. Sufficient IVIG should be given to maintain
      IgG trough levels of > 500 mg/dl; this usually requires a dose of 400 to 500
      mg/kg/month. Adverse side effects to IVIG has been described; the two most common
      serious side effects are hepatitis C and aseptic meningitis. New procedures to
      inactivate hepatitis C (and other viruses) are now in place. Aseptic meningitis
      is usually associated with high IVIG doses given rapidly to patients with
      autoimmune and inflammatory disease; its cause is not known. Subcutaneous
      infusions of IG or IVIG at weekly intervals has been shown to be clinically
      efficacious, well-tolerated and a less expensive alternative to monthly IVIG
      infusions. IVIG has been used with encouraging results in selected pediatric
      patients with HIV infection. The benefit is primarily in patients with CD4 counts
      > 200 cells/mm2 who receive no P. carinii pneumonia prophylaxis. IVIG may also be
      of value in preventing or ameliorating infection in other secondary antibody
      deficiencies including patients with malignancies; patients with protein-losing
      enteropathy and nephrotic syndrome; severely ill care patients with shock, trauma
      or surgery; premature infants and patients undergoing transplantation procedures;
      and severely burned patients. Guidelines for selecting patients for IVIG are
      offered.

PMID- 9239778
TI  - Typhoid fever in children: diagnostic and therapeutic difficulties.

PMID- 9239777
TI  - Immunity to Haemophilus influenzae type b after reimmunization with
      oligosaccharide CRM197 conjugate vaccine in children with human immunodeficiency
      virus infection.

PMID- 9239779
TI  - Fatal rhinoorbital mucormycosis caused by Saksenaea vasiformis in an
      immunocompromised child.

PMID- 9239780
TI  - Rifabutin ocular toxicity mimicking endophthalmitis.

PMID- 9239781
TI  - Intravenous immunoglobulin prophylaxis in an echovirus 6 and echovirus 4 nursery
      outbreak.

PMID- 9239782
TI  - Antigen excretion in the urine after pneumococcal vaccination.

PMID- 9239783
TI  - Protection from clinical varicella disease during interferon alpha-2a therapy for
      chronic active hepatitis B infection.

PMID- 9239784
TI  - The bug stops here: the school as health care provider.

PMID- 9239785
TI  - Varicella vaccination for adolescents with asthma.

PMID- 9239786
TI  - Urinary tract infection caused by Streptococcus mitis highly assistant to
      penicillin.

PMID- 9239787
TI  - The nasal saline flush procedure.

PMID- 9239788
TI  - Flaccid paralysis caused by botulinum toxin type B after pesto ingestion.

PMID- 9239789
TI  - Musical hallucinations and musical imagery: prevalence and phenomenology in
      schizophrenic inpatients.
AB  - The discussion of auditory hallucinations in schizophrenia has traditionally
      focused on verbal auditory hallucinations, or 'voices'. Little attention, on the
      other hand, has been given to the phenomenon of musical hallucinations. In an
      effort to characterize the prevalence and phenomenology of musical
      hallucinations, 100 consecutive schizophrenic inpatients were examined for the
      presence of musical hallucinations and musical imagery. Sixteen patients
      responded positively, and were engaged in a more thorough interview. They were
      then divided into two groups: those with musical hallucinations, and those
      experiencing musical imagery. This determination was made based on the absence or
      presence, respectively, of volitional control, hypothesizing that lack of
      volitional control implies a true hallucinatory experience. When lack of
      volitional control was compared to the various other aspects of the experience,
      an association with religious content was demonstrated. Religious musical
      hallucinations also tended to be experienced as distressing, further supporting
      the hypothesis that the experience was hallucinatory rather than a product of
      volitional imagery. A selection of sample case vignettes is presented as well.

PMID- 9239791
TI  - Influence of season on manifestation of schizophrenic subtypes.
AB  - In the modern classification systems ICD-10 and DSM-III-R, the term seasonality
      has been given a separate significance in the diagnostic categorization of
      affective disorders. Its definition is oriented not merely to the increased
      seasonal prevalence in the autumn and winter months, but also to symptoms that do
      not occur in nonseasonal attacks. To date, research work on seasonality in
      schizophrenia has concentrated on birth seasonality, while no results based on
      large populations of patients have yet become available on the manifestation
      seasonality of schizophrenic subtypes. Within the framework of a retrospective
      study carried out in the period between 1983 and 1995, involving 2, 119 patients
      suffering from recurrent attacks of schizophrenia, seasonal manifestations were
      recorded in accordance with the criteria defined in DSM-III-R. It was found that
      the two subtypes of paranoid hallucinatory and schizoaffective psychoses met the
      criterion of seasonality significantly more frequently than did the subtypes
      disorganized and catatonic disorders. In addition, seasonal courses within the
      groups just mentioned clearly differed from the nonseasonal forms in terms of
      their symptomatology.

PMID- 9239790
TI  - Symptoms of neuroses: profile patterns and factor structure of clinic attenders
      with non-psychotic functional psychiatric disorders.
AB  - Consecutively referred out-patients (n = 102) with non-psychotic functional
      psychiatric disorders were examined. Nine syndrome scores (panic attack, phobic
      anxiety, generalized anxiety, obsessive-compulsive, dissociative, conversion,
      somatoform, depersonalization, and depressive) showed patterns corresponding to
      ICD-10 diagnoses. However, some also showed moderate correlations between each
      other. Factor analysis revealed that the nine syndrome scores could be accounted
      for by three factors-anxiety and somatic, depression and obsessive-compulsive,
      and hysterical. These findings cast doubt on the nosological specificity of the
      recent categorization of neurotic disorders. Furthermore, the symptom
      constellations identified in this study may be culture-bound.

PMID- 9239792
TI  - Follow-up study of seasonal affective disorder in Switzerland.
AB  - Of 39 diagnosed Seasonal Affective Disorder (SAD) patients who were interviewed 2
      5 years after participation in a light therapy trial, 10 continued to have
      recurrent major depressive episodes in winter, and 17 manifested sub-syndromal
      SAD (2 patients also had recurrent brief depression, seasonal type). 8 patients
      had recovered, and 4 had shifted in symptomatology. Thus, over a number of years,
      the clinical diagnosis changed for the better in 64% of the patients, suggesting
      that SAD is not a prodromal form of a more chronic major affective disorder, and
      that light therapy (and perhaps also light-oriented behaviour) reduced the
      incidence and depth of subsequent depressive episodes. Further evidence for this
      was the large reduction in use of conventional antidepressant drugs (from 17 to
      1) during the follow-up period. Diagnosis of SAD was stable and reliable.

PMID- 9239793
TI  - Deboleza: culturally determined behaviour in Istria.
AB  - Deboleza is a behavioural construct among the inhabitants of Istria (a peninsula
      in the Adriatic Sea which belongs mainly to Croatia); it has peculiar social,
      ethno-psychological and historical characteristics because it is a relatively
      small region which has been the intersection of various cultures and
      civilizations. In this research the concept is analysed from the psychomedical
      point of view. As deboleza does not have the status of an illness, it functions
      as a culture-bound syndrome which, because of its emotional expressions, belongs
      to the 'shame' family. This interesting construct should be thoroughly studied
      not only in a peculiar and dynamic Croatian culture and in Croatian psychiatry,
      but also within European culture and psychiatry.

PMID- 9239794
TI  - Possession by the 'Zar' among Ethiopian immigrants to Israel: psychopathology or
      culture-bound syndrome?
AB  - The article describes a cultural pattern related to altered states of
      consciousness, observed amongst new immigrants from Ethiopia to Israel. The
      belief in possession by Zar spirits is one of the most common possession
      phenomena in Africa and in other continents. Possession by Zar is expressed by a
      wide range of behaviors, such as involuntary movements, mutism and
      incomprehensible language. Such behavior can be misinterpreted as representing
      symptoms of neuralgic or psychiatric disorders. We demonstrate the Zar phenomenon
      by a description of a detailed case. The article discusses the cultural and
      anthropological aspects of the Zar and its clinical implications and suggests
      that the Zar phenomenon should be understood as a culture-bound syndrome.

PMID- 9239795
TI  - Measuring treatment outcome by the Beck Depression Inventory.
AB  - The construct validity of the Beck Depression Inventory (BDI) in measuring
      treatment outcome is assessed in 103 psychiatric inpatients. In this context,
      construct validity means that the BDI measures the same construct in repeated
      measurement and that the change scores can be explained by treatment effects. In
      confirmatory factor analyses, only the first factor proved to be stable. In
      accordance with other studies, the sensitivity to therapeutic change in long-term
      intervals of several weeks could be confirmed. Significant changes in a short
      term interval of 1 day in the non-endogenously depressed patients indicate an
      overreactivity of the BDI to change which cannot be explained by treatment
      effects or mood changes.

PMID- 9239796
TI  - Psycholexicology: psychiatric discourse and nosological entities.
AB  - This paper presents the field of psycholexicology as an area of study concerned
      with etimology, meaning, and social legitimacy of the terms employed in
      psychiatric discourse, conceived of as the disciplinary foundation of clinical
      and research psychiatry. The influence of semantic constraints on structure and
      usage of psychopathological diagnosis is emphasized. Work in progress related to
      translation and cultural biases in terminology is briefly described.

PMID- 9239797
TI  - The effects of physical activity on rehabilitation for acute hepatitis.
AB  - We studied 19 patients with acute hepatitis who were instructed to follow a 5
      stage exercise regimen. The mean period of hospitalization was 31.9 days,
      slightly shorter than the mean duration for acute hepatitis patients. The
      exercise program had no adverse effects on the patients. They returned to works
      an average of 9.5 days after discharge, demonstrating a marked reduction in the
      rehabilitation period. Hepatitis should be primarily treated under the
      internist's management. However, physical exercise should be recognized as an
      equally important treatment modality.

PMID- 9239798
TI  - Study on ultrasonically guided fine-needle aspiration cytology for breast
      disorders with high-resolution transducer.
AB  - The author participated in the development annular array transducer. The author
      used this new device in 147 patients (aged 43.4 years ranging from 21 to 81
      years) and ultrasonically detected 193 breast lesions including 126 nonpalpable
      ones (65.3%). After that, the author performed 234 punctures for aspiration
      cytology using the same device and 22 gauge needle. The needle tip was
      intralesionally identified in 174 of the 234 punctures (74.4%) and 146 of the 193
      lesions (75.6%). The sensitivity, specificity and accuracy of cytological
      diagnosis were 72.7% (8/11), 91.2% (31/34) and 86.7% (39/45), respectively. No
      cell could be aspirated in 61 of the 146 lesions (41.8%). These results were
      comparable to those obtained from the conventional devices. Annular array
      transducer will increase the frequency of ultrasonic detection of small breast
      lesions. Fine needle aspiration cytology under ultrasonic guide with this new
      device will efficiently and speedily rule out malignant lesions and facilitate
      management of benign lesions at the outpatient department. This study suggests
      that ultrasonically malignant lesions should immediately be examined
      histologically without undergoing cytological examination. It should be noted
      that some cystic lesions are concentrated and accompanied by positive internal
      echoes. These cystic lesions show a change in size on the ultrasonic image after
      aspiration and contain paste- or gruel-like material.

PMID- 9239799
TI  - Immunodeficiency after allogeneic bone marrow transplantation in man: the role of
      antigen presenting cells.
AB  - We investigated the proliferative response of donor T cells to phytohemagglutinin
      (PHA) presented by donor non-T cells in 7 patients after allogeneic bone marrow
      transplantation. Compared with the cellular response in the healthy marrow
      donors, T cell proliferation was found to be deficient in every recipient, from
      130 to 739 days after grafting. Results of cell mixing experiments showed that
      the non-T cells of the patients were as capable as healthy donor non-T cells in
      presenting PHA to normal donor T cells. However, T cells from patients did not
      proliferate after substituting donor non-T cells for non-T cells from patients.
      This inability of T cells to proliferate was most likely the result of
      ineffective interactions among T cell subsets in patients after allogeneic bone
      marrow transplantation.

PMID- 9239800
TI  - Cytotoxic T cell activity after HLA-mismatch bone marrow transplantation.
AB  - Six patients with various hematologic diseases were treated with HLA
      haploidentical bone marrow mismatched for 1-2 loci at the disparate chromosome
      with a relative response in the mixed lymphocyte reaction (MLR) ranging between
      0.04 and 0.96 (median 0.27). Thirty to 371 days after bone marrow grafting,
      patient lymphocytes (of donor origin) were tested for reactivity in mixed
      lymphocyte culture (MLC) and cell mediated lympholysis (CMLy) to lymphocytes from
      the host (cryopreserved before grafting), the marrow donor, and unrelated
      individuals. After grafting, Lymphocytes from the patients showed a host-specific
      decrease in proliferation and in cytotoxic response (%51Cr release in a standard
      chromium release assay), when compared to the pretransplant host-specific donor
      response, whereas the responses towards third party cells were unaffected. This
      host-specific unresponsiveness after HLA-mismatch bone marrow transplantation is
      compatible with a clonal deletion theory and might be the reason that this
      procedure is at all possible.

PMID- 9239801
TI  - Infected aneurysms--clinical study of 5 cases.
AB  - The infected aneurysm has been assumed to be a disease with a poor prognosis due
      to the occurrence of aneurysmal ruptures and sepsis, in contrast to the outcome
      of atherosclerotic aneurysms. In the present study, we conducted surgical
      treatment on five patients with infected aneurysms (infected abdominal aortic
      aneurysm in three cases and iliac artery aneurysm in two cases). In particular,
      two of the three patients suffering from infected abdominal aortic aneurysms
      underwent extra-anatomic bypass and the remaining one case underwent vascular
      graft replacement in situ. In the two patients who underwent an extra-anatomic
      bypass, an aneurysm was found at the site of aortic stump closure. In the patient
      who underwent in situ replacement, wrapping was carried out using the omentum
      after vascular graft replacement, and the postoperative course was uneventful.
      Accordingly, we consider that the optimum primary therapeutic intervention for
      infected aneurysms is in situ revascularization followed by wrapping with the
      omentum after removal of the aneurysm and debridement of the surrounding infected
      tissue to the maximum extent possible.

PMID- 9239802
TI  - Acute emphysematous cholecystitis associated with pneumobilia: a case report.
AB  - This report describes a rare case of acute emphysematous cholecystitis with
      pneumobilia in the common bile duct. The patient was a 66-year-old woman with a
      part history of diabetes mellitus, and operations for gastric and breast
      carcinoma. The chief complaint was pain in the right hypochondrium with severe
      right hypochondrial tenderness and distention of the gallbladder detected on
      examination. Laboratory tests showed leukocytosis, marked elevation of CRP,
      jaundice, liver dysfunction, and hyperglycemia. Gas was detected in the
      gallbladder on plain abdominal X-rays and CT scans of the abdomen, and a small
      amount of gas was also observed in the common bile duct. On the day of admission,
      percutaneous transhepatic gallbladder drainage (PTGBD) was carried out under
      ultrasound guidance, and Clostridium perfingens and E. coli were detected in the
      bile. Imaging after PTGBD showed no cystic duct obstruction. On the 12th day
      after PTGBD, cholecystectomy and choledochotomy with primary closure were
      performed. The postoperative course was good and the patient was discharged on
      the 15th day after surgery.

PMID- 9239803
TI  - Effects of calyculin A and FK506 on the O2- generation of rat peritoneal
      macrophages.
AB  - To investigate the role of phosphatase in O2- generation, the effects of the
      potent phosphoprotein phosphatase inhibitors, Calyculin A and FK506, were
      analyzed during phagocytosis using rat peritoneal macrophages. O2- generation was
      continuously measured after addition of opsonized zymosan (op. ZY) or IgG-coated
      zymosan (IgG-ZY). The rate of O2- generation was directly proportional to the
      number of macrophages, up to 1-2 x 10(6) cells/ml. It was found that the rate and
      duration of O2- generation were markedly inhibited by Calyculin A. The addition
      of 100 nM of Calyculin A reduced O2- generation to about one-tenth of the control
      value. In contrast, FK506 did not inhibit O2- generation, suggesting that calcium
      calmodulin phosphatase is not involved in the activation of NADPH oxidase. This
      result indicates that the process of dephosphorylation might involve activation
      of NADPH oxidase as a control mechanism in phagocytosis by rat peritoneal
      macrophages. Furthermore, since Calyculin A is an inhibitor of phosphatase 1 and
      2A, it is suggested that dephosphorylation may be evoked by these phosphatases.

PMID- 9239804
TI  - Plasma and saliva concentrations of rifampicin in man after oral administration.
AB  - The saliva and plasma concentrations of rifampicin were determined following oral
      administration of 600 mg of the drug to healthy human subjects. Rifampicin is a
      zwitterion with PKa's of 1.7 and 7.9. The saliva-plasma concentration ratios
      calculated on the basis of the PKa of 1.7 was 1.6346. The saliva concentrations
      were much higher than the MICs of a variety of organisms, indicating the possible
      usefulness of rifampicin in the treatment of susceptible oropharyngeal and
      nasopharyngeal pathogens. After 24 hrs, when rifampicin was completely absent in
      the urine, the saliva and plasma concentrations also had fallen almost to zero.

PMID- 9239805
TI  - Effect of activated charcoal on rifampicin absorption in man.
AB  - The effect of activated charcoal (AC) on rifampicin excretion was investigated in
      six healthy volunteers. On three occasions, at weekly intervals, each subject
      received a 600 mg rifampicin with 350 ml of water; b+c one and two weeks later,
      600 mg of rifampicin plus 7.5 and 15 g AC, respectively, in 350 ml of water as a
      charcoal slurry. Urinary levels of rifampicin were measured form 1-36 hr after
      ingestion. Treatment with AC led to 1.2 per cent urinary recovery of rifampicin;
      decreased excretion rate; and a much lower plateau indicative of reduced
      absorption.

PMID- 9239806
TI  - Immunolocalization of glutathione-peroxidase (GSH-PO) in the rat ventral
      prostate: effects of castration and administration of testosterone.
AB  - Immunolocalization of glutathione-peroxidase (GSH-PO) in the rat ventral prostate
      was studied in the presence and absence of androgen. Male Sprague-Dawley rats
      were divided into four experimental groups. Group 1 consisted of intact controls.
      In group 2, rats were sacrificed two days after castration. In groups 3 and 4,
      rats were injected subcutaneously with 1 mg of testosterone-propionate daily, for
      three or seven days, beginning two days after castration. The intensity of GSH-PO
      staining in the glandular epithelial cells of the ventral prostate decreased
      after castration, but recovered following treatment with testosterone.
      Furthermore, the prostatic GSH-PO mRNA levels were diminished in the castrated
      rat ventral prostate but greatly increased by testosterone. These findings
      strongly suggest that the expression of GSH-PO in the glandular epithelial cells
      of the rat ventral prostate is dependent on testosterone.

PMID- 9239807
TI  - Chelerythrine inhibits the secretory response of human blood platelets without
      specifically inhibiting protein kinase C.
AB  - Chelerythrine (chloride) has previously been documented to be a potent and
      selective inhibitor of the serine/threonine-specific protein kinase C (PKC). In
      this study, it was shown that 10 microM chelerythrine completely inhibited
      serotonin secretion and partially inhibited phosphatidic acid formation in human
      blood platelets activated by thrombin (1U/ml). However, there was no effect on
      PKC activity as assessed by the level of phosphorylation of the 47K protein.
      Therefore, chelerythrine has been shown not to be a specific inhibitor of PKC.
      Without specifically affecting PKC activity, it is nevertheless capable of
      completely inhibiting platelet secretion, indicating that it may affect the
      signal transduction pathway responsible for platelet secretion at a point
      downstream or independent of PKC.

PMID- 9239808
TI  - Early skin response to fractionated doses of pions for determining therapeutic
      gain factors.
AB  - This study concerns the biological effectiveness of fractionated doses of pions
      on early skin reactions near the implanted tumor, to evaluate the therapeutic
      gain factors of pions. The C3H mouse limbs bearing microscopical SCCVII tumors
      were irradiated with pions (9.6-38.4 Gy) or x-rays (14.4-50.4 Gy) in 2-7
      fractions. Nicotinamide (500 mg/kg) and carbogen (a mixture of 95% O2 + 5% CO2),
      as hypoxic radiosensitizers, were administered prior to the x-rays, to confirm
      the presence of hypoxic cells in the skin. The mean skin scores and number of
      damaged nails assessed. The ratios of x-ray/pion doses needed for giving
      comparable skin reactions were 1.3-1.5. Nicotinamide and carbogen enhanced the
      skin reactions. When the ratios were compared with those of tumor cure, the pions
      showed no therapeutic gains. One of the possible causes was that the presence of
      hypoxic cells in the skin may have reduced the therapeutic gain.

PMID- 9239809
TI  - Modulation of peripheral blood lymphocyte subsets during methylprednisolone pulse
      therapy.
AB  - We determined fluctuations in circulating lymphocyte subsets induced by
      methylprednisolone pulse therapy (MPT) and the continuous administration of
      prednisolone (PSL) in 17 patients with autoimmune or systemic rheumatic disease.
      Two-color flow cytometry, using monoclonal antibodies to various lymphocyte
      subsets, was performed to identify a possible association between the clinical
      efficacy of treatment and modulative effects on each subset. Both MPT and
      continuous oral PSL showed suppressive effects on most of the lymphocyte subsets:
      CD4+, CD45RA or CD45RA+CD4+, CD8+, CD11b.CD8+, CD5+ B, and CD57+ or CD57 CD16+
      cells. Modulation of lymphocyte subsets were more profound with MPT than with
      continuous oral PSL. The results are relevant to the different degrees of immuno
      suppression effected by the two treatment modalities. We found that the number of
      CD45RA.CD4+ cells after MPT treatment correlated with the clinical efficacy of
      the treatment: the less CD45RA.CD4+ cell numbers decreased after MPT treatment,
      the greater was the clinical efficacy of the treatment. The results probably are
      associated with a rapid recovery of the subset after MPT treatment in the
      responders. Thus, the sequential monitoring of circulating lymphocyte subsets is
      useful in predicting the clinical effects of MPT treatment.

PMID- 9239810
TI  - A case of microhepatoma associated with schistosomiasis japonica diagnosed by
      enhanced ultrasonography after hepatic intraarterial injection of carbon dioxide
      gas.
AB  - The patient was a 58-year old man whose complaints were generalized malaise and
      right epigastralgia. He had liver cirrhosis and schistosomiasis japonica,
      previously diagnosed by laparoscopy. Computed tomography (CT) showed a high
      density funicular shadow in the liver. However no tumorous lesions in the liver
      were visualized. Ultrasonography (US) of the liver showed a reticulate or scaly
      pattern, but no images of tumorous lesions. Hepatic angiography showed a single,
      deeply colored image about 1cm in diameter, in the segmentum anterosuperior.
      Preoperative and intraoperative enhanced US with hepatic intraarterial injection
      of carbon dioxide gas was performed. It showed a hyperechoic tumor shadow about
      1cm in the segmentum anterior. The segmentum anterosuperior including the tumor
      was partially resected. Pathologically, the tumor was found to be a hepatoma of
      Edmondson type II, caused by cirrhosis and schistosomiasis japonica. The
      patient's postoperative course was uneventful. Enhanced US with hepatic
      intraarterial injection of carbon dioxide gas was useful for the diagnosis and
      treatment of the microhepatoma associated with schistosomiasis japonica.

PMID- 9239811
TI  - Post-thyroidectomy hypocalcemia: the role of calcitonin, parathormone and serum
      albumin.
AB  - To investigate the pathogenesis of post-thyroidectomy hypocalcemia calcium,
      phosphate, calcitonin, parathormone, albumin, triiodothyronine and thyroxine
      levels were monitored during operation and postoperatively in 25 female patients
      undergoing bilateral subtotal thyroidectomy for non-toxic nodular goiter. A
      highly significant fall in uncorrected serum calcium and albumin levels started
      with the completion of lobectomies and a significant correlation between the
      course of serum calcium and albumin levels were seen, an early peak in calcitonin
      corresponded well with the a drop in corrected calcium and inorganic phosphate
      levels. An overt parathyroid response to hypocalcemia was not observed. We
      conclude, on the basis of the postoperative hypoalbuminemia, that a calcitonin
      leak triggered the early onset of hypocalcemia while an insufficient parathyroid
      response contributed to the post-thyroidectomy hypocalcemia.

PMID- 9239813
TI  - Use of epidural anesthesia in non-cardiac surgery in two cases complicated by
      hypertrophic cardiomyopathy.
AB  - Two patients with hypertrophic cardiomyopathy (HCM) who underwent non-cardiac
      surgery were managed successfully using epidural anesthesia as the principal
      intraoperative anesthesia. Epidural block was induced by inserting an epidural
      catheter from the lumbar vertebrae toward the caudal side. Epidural anesthesia is
      usually avoided in HCM patients because of the risk of a decreased preload or
      afterload causing stenosis in the left ventricular outflow tract. However, in
      surgery that requires an anesthesia level at L1 or below, which has little effect
      on sympathetic nerves, epidural anesthesia that maintains a stabilized
      hemodynamic state appears to be an excellent option.

PMID- 9239812
TI  - Comparison of topical silver nitrate and flunisolide treatment in patients with
      idiopathic non-allergic rhinitis.
AB  - In this study, 90 patients with idiopathic non-allergic rhinitis were divided
      into three groups. Silver nitrate was given to Group I, flunisolide to Group II,
      and placebo to Group III. Healing results according to symptoms, physical
      findings, nasal smear findings and biopsy findings were compared. Improvement ws
      noticed in symptoms (rhinorrhea 93%, sneezing 89%, nasal congestion 80%),
      physical findings (color of mucosa 89%, concha hypertrophy 87%, rhinorrhea 82%),
      nasal smear findings (94%) and biopsy findings (epithelium 76%, basal membrane
      80%, edema 84%, eosinophilia 95%, inflammation 87%) in Group I. Recurrence was
      observed in symptoms and physical findings of 30% of the patients in Group I
      during the 6 months-follow-up period. In Group II, improvement was noticed in
      symptoms (rhinorrhea 73%, sneezing 70%, nasal congestion 61%), physical findings
      (color of mucosa 72%, concha hypertrophy 69%, rhinorrhea 62%), nasal smear
      findings (87%) and biopsy findings (epithelium 67%, basal membrane 63%, edema
      70%, eosinophilia 77%, inflammation 70%). But symptoms recurred in all patients
      in approximately 1-3 months after competition of treatment. There was a
      statistically significant difference between silver treatment and flunisolide or
      placebo treatment.

PMID- 9239814
TI  - Seroepidemiological studies on Silk Road ethnic groups.
AB  - To clarify the origin of the Japanese, the Jomom and/or Yayol, we screened for
      HTLV-1 and -II antibodies among inhabitants of the Silk Road, the Han, Uygur and
      Kazaks. We also screened for HIV, HBV, and HCV. The HTLV-I, -II, HIV, and HCV
      antibody tests were uniformly negative in all the studied groups. In contrast, a
      significantly higher incidence of HBs antigen was observed in all the groups
      tested (Northern Han: 11.9%, Uygur: 6.0%, Kazak: 9.1%). These results indicate
      that these ethnic groups are not the origin of the indigenous Japanese (the
      Jomon), and that HBV is prevalent in the various groups along the Silk Road.

PMID- 9239815
TI  - Decay-accelerating factor (DAF, CD55)-negative T lymphocytes in the peripheral
      blood of Sjogren's syndrome patients.
AB  - OBJECTIVE: To clarify possible associations of decay-accelerating factor (DAF,
      CD55), expressed on circulating lymphocyte subsets and other hematologic cells,
      with corresponding cytopenias observed in primary Sjogren's syndrome (SS).
      METHODS: DAF expression on peripheral blood (PB) cells was determined in 21
      patients with SS and 11 healthy controls by single or 2 color flow cytometry.
      RESULTS: In the PB from SS patients, anemia, monocytopenia, neutropenia, and
      lymphocytopenia were observed. Compared to the controls, the percentages of DAF
      negative cells were higher in CD4+ and CD8+ T cell subsets from SS patients, but
      the expression of DAF was similar in the other PB cells, including CD19+ B cells,
      CD56+ NK cells, monocytes, granulocytes, and erythrocytes. The percentages of DAF
      negative cells among the CD4+ and CD8+ cells were positively correlated in SS
      patients, but the numbers of cells in both subsets were decreased in those
      patients being treated with prednisolone. However, these proportional changes are
      thought to reflect a decrease in the numbers of DAF-positive CD4+ and CD8+ cells,
      because the absolute numbers of circulating DAF-positive CD4+ and CD8+ cells, but
      not DAF-negative cells, were significantly decreased in SS patients. In addition,
      DAF-negative cells were detectable in both CD45RA+ (naive) and CD45RO+ (memory) T
      cells from healthy individuals, and the expression of DAF was remarkably
      increased in both subsets after in-vitro activation with concanavalin-A.
      CONCLUSION: DAF-negative cells are proportionally increased among circulating
      CD4+ and CD8+ T cells in SS patients, although such changes are due to decreased
      numbers of DAF-positive cells within each subset. When considering previous
      observations, the DAF-negative CD4+ and CD8+ cells probably belong to activated T
      cell subsets in both SS patients and controls. However, the patterns of DAF
      expression seemed to be different between activated T cells recognized in the PB,
      and those induced by in vitro-stimulation.

PMID- 9239816
TI  - An experimental study on an evaluation method for occupational therapy--the
      effectiveness of a newly developed computerized measurement system of finger
      function.
AB  - We developed a new computerized measurement system of finger function as a
      movement test. This type of measurement system is very novel in the field of
      occupational therapy. Eighty-seven healthy individuals and 101 patients
      participated in this study to investigate the effectiveness of the new system.
      The subjects were asked to test their eye-hand coordination by operating a joy
      stick lever. The following findings were obtained. 1) A computerized measurement
      system of finger function was developed and effectiveness was improved. 2)
      Correlation between their age and finger function in the healthy group was 0.409,
      and 0.407 in the patient group. 3) The relationship between the time of testing
      and performance was stable in the healthy group throughout the measurements,
      while in the patient group, deviations from the value in the initial 5 seconds
      grew larger with the time of testing (p < .01). 4) In the hemiplegia patients,
      the performance level of the left hemiplegia group was lower than that of the
      right hemiplegia group (p < .01). By means of a computer analysis, it was
      confirmed that characteristics of individual finger function can be clarified in
      greater detail. The possibility of general application of this system in
      evaluation of the effects of occupational therapy were suggested.

PMID- 9239817
TI  - Endoscopic screening for esophageal cancer in 788 patients with head and neck
      cancers.
AB  - Esophageal cancer has a poor prognosis because it is difficult to detect in its
      early stages and, even if an operation is possible, the postoperative quality of
      life is much impaired. An early diagnosis can lead to a good prognosis and
      enables treatment by endoscopic mucosal resection (EEMR), contributing to a
      postoperative good quality of life. As head and neck cancers are known to have a
      high risk of concomitant esophageal cancer, endoscopic screening with iodine
      staining was performed on 788 patients with head and neck cancers. Among them, 93
      cases of esophageal cancers (11.8%) and 23 cases of gastric cancers (2.9%) were
      detected. Seventy-two cases (77.4%) of the 93 esophageal cancers were superficial
      cancers limited to the submucosal layer. Twenty cases, treated by EEMR, had a
      good postoperative course without local recurrence. We suggest that endoscopic
      screening for esophageal cancer should be performed on all patients with head and
      neck cancers, because it allows early detection and a good prognosis, and the
      treatment can be completed by endoscopic maneuver.

PMID- 9239818
TI  - Respiratory impedance estimated from airway and intrapleural pressure curves.
AB  - At the cessation point of inspiratory flow on an airway pressure curve of
      constant-flow CMV (controlled mechanical ventilation), the pressure falls rapidly
      at first and then gradually tapers down to an endinspiratory plateau. By fitting
      these two pressure changes to the voltage changes in the respiratory circuit
      model, the resistance and compliances in the lung periphery and the resistance in
      the large airway can be estimated. We designed an algorithm estimating the values
      of circuit elements using a circuit simulator MicroCap III. The validity of this
      method was examined on the mechanical lung model. The sensitivity came to within
      +/- 15%. Further validation was carried out on five Beagles treated with
      methacholine. The large airway resistance, the small airway resistance and
      compliance, and alveolar compliance demonstrated a two- to three-fold increase in
      resistances and a two thirds to one-half decrease in compliances, when compared
      with the base-line values before administration of methacholine. This method can
      be applied not only to patients during CMV, but also during surgery.

PMID- 9239819
TI  - Dating of pregnancy: time to forget the last menstrual period.

PMID- 9239820
TI  - In a different vein: the ductus venosus could yield much valuable information.

PMID- 9239821
TI  - Assessing skeletal development.

PMID- 9239822
TI  - The prevalence and clinical significance of tricuspid valve regurgitation in
      normally grown fetuses and those with intrauterine growth retardation.
AB  - The aim of this study was to assess the prevalence and clinical significance of
      fetal tricuspid valve regurgitation. In a cross-sectional study, 289 normally
      grown singleton fetuses with normal heart anatomy, normal estimated weight for
      gestational age, normal amniotic fluid volume and normal flow velocity waveforms
      in the umbilical and middle cerebral arteries and umbilical vein were examined. A
      further 31 singleton fetuses with intrauterine growth retardation (estimated
      fetal weight below the 3rd centile) were analyzed. Semiquantification of the
      tricuspid valve regurgitation by spatial and temporal parameters was performed in
      the four-chamber view by color Doppler flow imaging and by color Doppler M-mode
      echocardiography (M-Q mode). The prevalence of fetal tricuspid valve
      regurgitation among normally grown fetuses was 6.23% (n = 18). In all cases, the
      tricuspid regurgitation was part-systolic (non-holosystolic, early and mid
      systolic tricuspid regurgitation) and showed little spatial expansion of the jet
      as examined by color Doppler flow imaging (no jet reached the opposite atrial
      wall, the area of tricuspid regurgitation being less than 25% of the atrial
      area). The maximum velocity of the regurgitant jets was below 2 m/s with one
      exception. There was no statistically significant correlation between gestational
      age and occurrence of tricuspid regurgitation (U test, p > 0.05). Re-examination
      of 14 of the 18 fetuses with tricuspid regurgitation showed that tricuspid
      regurgitation was a transient phenomenon in these instances. The fetal outcome in
      the presence of tricuspid valve regurgitation was normal. Regurgitations of the
      mitral, pulmonary and aortic valves were excluded in all 289 fetuses. Only two of
      the 31 fetuses (6.45%) with intrauterine growth retardation showed tricuspid
      valve regurgitation. In one fetus the tricuspid regurgitation ws only part
      systolic. In the other severely compromised fetus with highly abnormal flow
      velocity waveforms in the arterial and venous side of the fetal circulation,
      cardiac dilatation with holosystolic tricuspid and holosystolic mitral
      regurgitation occurred immediately before intrauterine death. Fetal tricuspid
      valve regurgitation was a frequent finding during Doppler echocardiography.
      Although it may be a sign of increased preload, afterload or cardiac dysfunction,
      in most cases tricuspid valve regurgitation is an isolated transient finding with
      little temporal and spatial expansion, and it may be physiological.

PMID- 9239823
TI  - Hemodynamic changes across the human ductus venosus: a comparison between
      clinical findings and mathematical calculations.
AB  - We investigated the hemodynamics of the ductus venosus in the human fetus by
      means of a combined approach based on Doppler and computational techniques. The
      aim of our study was to assess the blood velocity changes across the ductus
      venosus. Color Doppler equipment was used to investigate 29 normal fetuses
      between 20 and 39 weeks of gestation. Velocities at the systolic peak (S),
      diastolic peak (D) and atrial contraction (A) were measured at the isthmus and at
      the outlet of the ductus venosus, and the corresponding angle-independent indices
      (S/A, (S-A)/S, (S-A)/D) were calculated. A parametric computational model was
      developed in order to investigate the influence of anatomical features of the
      ductus venosus on the hemodynamics of the vessel. In all the fetuses the S, D and
      A velocities at the outlet portion were significantly lower than those at the
      isthmic part of the ductus venosus (p < 0.0001). The mean percentages of velocity
      reduction were 23.1%, 26.5% and 33.6%, respectively. Computational simulations
      also showed a relevant decrease of the velocity along the ductus venosus during
      the whole cardiac cycle. Velocity reduction along the ductus was mainly due to
      its conicity and this reduction generally caused velocity values at the outlet to
      be below the normal range. Conversely, angle-independent indices measured both at
      the isthmus and at the outlet lay within the same range of the reported reference
      values and therefore were not influenced by sampling site.

PMID- 9239824
TI  - Ultrasonographic and radiologic visualization of the developing embryonic
      skeleton.
AB  - We investigated the development of the skeleton in the embryonic and early fetal
      period both with ultrasonography and radiology. Eight normal embryos/fetuses were
      studied weekly with real-time transvaginal sonography between 8 and 16 weeks of
      gestation to establish the ultrasonographic characteristics of normal
      ossification. Additionally, ossification was studied in radiographs obtained from
      five embryos/fetuses between 9 and 14 weeks of gestation. Ossification centers,
      visualized as increased echogenicity of the bone, were recognized with
      ultrasonography from 9 weeks onwards. The appearance of primary ossification
      centers as observed by transvaginal ultrasonography was at the same gestational
      age or at most 1 week later than when obtained with radiography or whole-specimen
      staining techniques. Transvaginal ultrasonography enables early visualization of
      ossification centers in the embryo and fetus. Detailed knowledge of the
      development of ossification of the skeleton may contribute to early prenatal
      diagnosis of skeletal dysplasias.

PMID- 9239825
TI  - Fetal hemoglobin changes in the twin oligohydramnios-polyhydramnios sequence.
AB  - Fetal hemoglobin concentration was measured in each twin from five monochorionic
      pregnancies complicated by twin-to-twin transfusion, diagnosed by growth
      discordance and coexistent oligohydramnios-polyhydramnios. In three cases the
      hemoglobin concentration of the smaller twin with oligohydramnios was lower than
      the normal mean for gestation, and the hemoglobin difference was more than 5 g/dl
      in two of these cases. In the other two cases, the hemoglobin concentration of
      the four fetuses with coexistent oligohydramnios-polyhydramnios was within the
      normal range. This suggests that twin-to-twin transfusion may occur without
      hemoglobin changes, or that alternatively coexistent oligohydramnios
      polyhydramnios occurs in the absence of twin-to-twin transfusion.

PMID- 9239826
TI  - Receiver operating characteristic curves of sonographic estimated fetal weight
      for prediction of macrosomia in prolonged pregnancies.
AB  - We evaluated areas under receiver operating characteristic curves for sonographic
      estimated fetal weight (EFW) as a predictor of macrosomia in prolonged
      pregnancies. These areas were 0.85 for birth weights of > or = 4000 g and 0.95
      for birth weights of > or = 4500 g. Both were significantly greater than 0.5, the
      area under curves for useless tests. Areas under curves before and after
      adjustment for time elapsed between measurement and delivery did not differ
      significantly. At the inflexion point cut-off level of 3711 g, sensitivity,
      specificity and positive and negative predictive values of EFW for birth weight
      of > or = 4000 g were 85, 72, 49 and 94%, respectively. At the inflexion point
      cut-off level of 4192 g for birth weight of > or = 4500 g, these values were 83,
      92, 30 and 99%. The relative risk for birth weight of > or = 4000 g was 7.99, and
      for birth weight of > or = 4500 g, 39.50, both significant. In conclusion,
      sonographic EFW is a useful test for predicting macrosomia. Adjustment for time
      elapsed did not significantly improve either test, probably because of slow rates
      of fetal growth at this gestational age. Cut-off values derived from this
      analysis result in high sensitivity but low positive predictive value. A
      randomized controlled trial of mode and timing of delivery for predicted
      macrosomia is needed.

PMID- 9239827
TI  - Incorporating sonographic cheek-to-cheek diameter, biparietal diameter and
      abdominal circumference improves weight estimation in the macrosomic fetus.
AB  - The objective of this study was to improve the accuracy of sonographic fetal
      weight estimation in macrosomic (> 4000 g) fetuses by combining the cheek-to
      cheek diameter (CCD), an indicator of subcutaneous tissue mass, with the
      biparietal diameter (BPD) and abdominal circumference (AC) in generating a new
      weight formula. Three hundred well-dated, uncomplicated singleton pregnancies >
      32 weeks' gestational age (GA) were analyzed. Sonographic fetal measurements
      obtained in every case included BPD, head circumference, AC, femur length and
      CCD. Sonographic estimation of fetal weight (EFW) was derived by using BPD and
      AC. Actual birth weights (BW) of fetuses delivered within 7 days of the last
      sonographic examination and weighing over 1500 g (n = 123) were compared to EFW.
      A formula was derived by correlating BPD, AC and CCD with BW in these 123 fetuses
      using multiple regression analysis. A second formula was derived from the data of
      39 macrosomic fetuses. The two formulae were then tested for accuracy of
      prediction of fetal weight in 157 other fetuses delivered within 7 days and
      grouped by birth weight, 44 of them weighing > 4000 g. The new formula for
      macrosomic fetuses was: EFW (g) = 1065 + 84.5 BPD (cm) + 41.29 AC (cm) + 111.0
      CCD (cm). In the macrosomic fetuses, a difference of < 10% between EFW and BW was
      demonstrated in 72.7% by the BPD-AC formula and 95.5% when incorporating CCD. In
      this group, the mean percentage error was significantly smaller: 4.14 vs. 7.97%
      (p = 0.0005). In the regression analysis, the contributions of BPD, AC and CCD to
      the variance in BW were 5.5%, 16%, and 18.3%, respectively (p = 0.008). In the
      non-macrosomic fetuses, CCD improved prediction of BW, but the trend did not
      reach statistical significance. Our results demonstrate that, in the macrosomic
      fetus, CCD explains more of the variance in BW than other parameters and
      incorporating it in the sonographic weight estimation greatly improves its
      accuracy.

PMID- 9239828
TI  - Ultrasonography of the ureter during laparoscopic gynecological surgery.
AB  - The purpose of this study was to evaluate the ultrasonographic appearance and
      normal function of the ureter during gynecological surgery. The study group
      consisted of 14 gynecological patients scheduled for laparoscopy and 12 patients
      scheduled for laparotomy. Under standardized anesthesia conditions before pelvic
      surgery, the appearance, location, dimensions and peristaltic activity of the
      ureter were examined using a 7.5-MHz flexible laparoscopic linear transducer
      probe. Imaging of the ureter was possible in all cases. The ureteral lumen,
      mucosa, subepithelial connective tissue and muscular layer could be imaged as a
      tubular structure with low-level echoes. The separate layers, however, could not
      be differentiated by ultrasonography. The ureteral diameters at resting phase did
      not differ between the open surgery and laparoscopy groups. During peristaltic
      activity the maximal diameter was smaller in the laparoscopy group. The mean
      number of peristaltic waves was 23 +/- 7 waves per 5 min and this did not differ
      significantly between the open and laparoscopic surgery groups. Intermittent
      periods of retrograde flow were detected in 21 of the 26 patients. As seen in
      this study, ureteral location and function can be ultrasonographically evaluated
      during surgery and laparoscopic conditions do not have much influence on the
      ureter. The role of laparoscopic ultrasonography in lowering the incidence of
      ureteral complications in gynecological surgery needs further study.

PMID- 9239829
TI  - Late prenatal ultrasound features of hydrometrocolpos secondary to cloacal
      anomaly: case reports and review of the literature.
AB  - Cloacal anomalies are extremely rare and have variable presentations. Prenatal
      diagnosis can be difficult especially if they present in late gestation. Here we
      present two cases diagnosed in the late third trimester and review the literature
      regarding prenatal diagnosis of cloacal anomalies.

PMID- 9239830
TI  - Unusual fate of vesicoallantoic cyst with non-visualization of fetal urinary
      bladder in a case of patent urachus.
AB  - We present the sonographic findings of a fetus with a vesicoallantoic cyst. The
      cyst was first identified at 17 weeks of gestation; it was associated with an
      omphalocele, and disappeared spontaneously at 29 weeks. The fetal urinary bladder
      was not visualized thereafter. An omphalocele and exstrophia of the urachus were
      found at birth and repaired. Non-visualization of the fetal urinary bladder
      suggested rupture of the covering membrane of the omphalocele and allantois
      during fetal life. A defect in the wall of the omphalocele supported our
      hypothesis.

PMID- 9239831
TI  - Prenatal identification of a completely cystic internal sacrococcygeal teratoma
      (type IV).
AB  - Sacrococcygeal teratomas can be diagnosed prenatally with a detailed ultrasound
      examination of the fetal anatomy. The majority of these teratomas are solid or
      mixed cystic and solid external caudal masses. A conclusion drawn from the
      literature is that only a small percentage are entirely cystic and few are
      completely internal or presacral without external component (Type IV). This
      report describes an unusual case of a large completely internal cystic
      sacrococcygeal teratoma identified prenatally by ultrasonography at 32 weeks'
      gestation. The differential diagnosis for this unique presentation of
      sacrococcygeal teratoma is different from that considered for predominantly
      external complex tumors.

PMID- 9239832
TI  - Is there a fetal brain-sparing effect in pre-eclampsia?

PMID- 9239833
TI  - Immunophenotype of the canine transmissible venereal tumour.
AB  - The canine transmissible venereal tumour is a naturally occurring contagious
      round-cell neoplasia which is primarily located in the mucous membrane of the
      external genitalia in dogs of either sex. In order to specify the controversial
      cytogenetic origin of this round-cell tumour, 14 cases of canine transmissible
      venereal tumour, formalin- or Bouin-fixed and paraffin-embedded, were subjected
      to extensive immunophenotypic analysis using reagents specific to a variety of
      cytoplasmic or surface antigens: lysozyme, ACM1 antigen, vimentin, neuron
      specific enolase, glial fibrillary acidic protein, desmin, alpha smooth muscle
      actin, CD3, IgG, kappa and lambda light chains, and keratin. Lysozyme
      immunoreactivity was detected in all cases, ACM1 antigen in 11 of 14, neuron
      specific enolase in 11 of 14, vimentin in 10 of 14, glial fibrillary acidic
      protein in 4 of 14 and desmin in 1 of 14. All the sections were negative to
      keratins, alpha smooth muscle actin and CD3, whereas in five cases, perivascular
      tumour cells contained Ig G, kappa and lambda light chains. The immunoreactivity
      to lysozyme and ACM1 antigen supports the hypothesis of a histiocytic
      immunophenotype for the canine transmissible venereal tumour.

PMID- 9239835
TI  - Focal mesangial-sclerosing glomerulonephritis and acute-spontaneous infectious
      canine hepatitis: structural, immunohistochemical and subcellular studies.
AB  - The glomerular alterations observed in a dog with acute spontaneous infectious
      canine hepatitis (ICH) are described. Histologic changes of the glomeruli were
      enlargement of the mesangium with presence of intranuclear inclusion bodies and
      without proliferation of mesangial cells. Electron microscopy revealed adenovirus
      replication sites in glomerular mesangial cells and in endothelial cells of
      glomerular capillaries, as well as a focal mesangial-sclerosing
      glomerulonephritis associated with electron dense deposits which were closely
      related with extracellular ICH viral particles and immunohistochemically reactive
      for immunoglobulin (Ig) G, IgA, IgM and C3c complement components.

PMID- 9239834
TI  - Immunophenotyping of skin-infiltrating T-cell subsets in dogs with atopic
      dermatitis.
AB  - Atopic dermatitis in dogs has many clinical features that are identical to those
      of the same disorder in man. To investigate the pathogenesis of this disease in
      dogs and the possibility of similarities to the pathogenesis in humans we
      compared the presence and ratio of CD4+ and CD8+ T-cells in the cutaneous
      infiltrate of lesional and non-lesional skin of atopic dogs with that in the skin
      of healthy dogs. In ten dogs with atopic dermatitis and ten healthy dogs the skin
      was biopsied at the predilection sites for atopic dermatitis and histological
      sections were immunohistochemically stained for CD4 and CD8. The staining showed
      an increase in CD4+ and CD8+ T-cells in canine lesional atopic skin, with a
      predominance of CD4+ T-cells in the epidermis. In non-lesional atopic skin there
      was also an infiltration with CD4+ and CD8+ T-cells, but without predominance of
      CD4+ T-cells. The results in the separate predilection sites did not differ
      substantially from the mean results. These observations indicate further
      similarities in the immunopathogenesis of atopic dermatitis in dogs and humans,
      which may have consequences for the control of atopic dermatitis in dogs and
      contributes to a possible role of the dog as a model for human atopic dermatitis.

PMID- 9239836
TI  - Tumor necrosis factor-alpha production and disease severity after immunization
      with enriched major core protein (p26) and/or infection with equine infectious
      anemia virus.
AB  - Cardinal features of equine infectious anemia (EIA) include fever, hemolytic
      anemia and thrombocytopenia during the acute phase of the disease, and cachexia
      and anemia seen during the chronic phase. These signs are thought to result from
      the release of inflammatory cytokines such as TNF-alpha. In order to determine if
      TNF-alpha has a role in the pathogenesis of acute EIA and vaccine-induced disease
      enhancement, we measured plasma concentrations of TNF-alpha in ponies immunized
      with virus enriched major core protein-p26 and/or experimentally infected with
      EIAV. Naturally infected inapparent EIAV carriers were also studied. TNF-alpha
      levels were determined by means of a WEHI 164, clone 13 cytotoxicity assay. We
      show a significant positive temporal correlation between TNF-alpha levels,
      severity of symptoms (fever and thrombocytopenia) and viremia. Furthermore, TNF
      alpha levels also correlate with strain virulence and the disease enhancement
      seen in vaccinated ponies. Of this group of animals, those challenged with a
      heterologous virulent strain presented the most unfavorable outcome as well as
      the highest levels of TNF-alpha and viremia. The TNF-alpha activity observed in
      the bioassay was completely abrogated by a polyclonal rabbit anti-human TNF-alpha
      antiserum, thus confirming the specificity of the plasma cytotoxicity. Our
      observations indicate that TNF-alpha production correlates with the outcome of
      infection with EIAV.

PMID- 9239837
TI  - Acquired B lymphocyte deficiency and chronic enterocolitis in a 3-year-old
      quarter horse.
AB  - This case report describes a 3-year-old American Quarter Horse with acquired
      immunodeficiency. Clinical signs included chronic diarrhea due to Salmonella
      typhimurium and bacterial pneumonia. Characterization of the immunodeficiency
      involved in vivo phytohemagglutinin (PHA) intradermal testing, in vitro
      lymphocyte proliferation in response to concanavalin A, immunofluorescence flow
      cytometry data on blood lymphocytes, serum protein electrophoresis and
      immunoglobulin (Ig) quantification. A diagnosis of B lymphocyte deficiency with
      resulting deficiencies in serum IgG, IgA and IgM and a concurrent decrease in T
      cell function was made based on these tests. Postmortem examination revealed no
      evidence of lymphosarcoma. This case represents a variation of young adult-onset
      B cell deficiency not previously described in the literature.

PMID- 9239839
TI  - Induction and suppression of lymphocyte proliferation by antigen extracts of
      Ostertagia ostertagi.
AB  - To obtain an insight into the responses of T-cells of cattle to Ostertagia
      ostertagi, the responses of peripheral blood and lymph node lymphocytes to O.
      ostertagi antigen extracts were determined in both exposed and naive calves. The
      lymphocyte responses induced by O. ostertagi antigen extracts of the third (L3)
      and fourth (L4) larval stages, as well as adult worms, were analysed. Although
      peripheral blood lymphocyte responses were very low or absent, abomasal lymph
      node lymphocytes of exposed animals showed a strong response to the L3 antigen
      extract. No such response was observed in naive calves or in mesenteric lymph
      node cells of exposed calves. L4 and adult worm antigen extracts suppressed the
      proliferative responses induced by the L3 antigen extract. Whether or not this
      suppressive effect plays a role in the slow rate at which protective immunity
      develops against O. ostertagi is under further investigation.

PMID- 9239838
TI  - Antigen-induced interferon-gamma and interleukin-2 responses of cattle inoculated
      with Mycobacterium bovis.
AB  - Bovine purified protein derivative (PPD)-induced interferon-gamma (IFN-gamma) and
      interleukin-2 (IL-2) mRNA expression was measured in peripheral blood lymphocyte
      cultures of cattle inoculated with Mycobacterium bovis and compared to cytokine
      protein levels as measured by IFN-gamma enzyme-linked immunosorbent assay and IL
      2 bioassay. For individual animals, positive correlations were observed between
      mRNA and protein levels of bovine PPD-induced IFN-gamma and IL-2, although the
      correlations were stronger for IFN-gamma. Expression of these two cytokines also
      correlated with responses from a comparative intradermal test and a M. bovis
      antibody test. At 7 and 20 weeks after inoculation, bovine PPD-induced IFN-gamma
      and IL-2 mRNA expression was detected in all animals with tuberculous lesions and
      in a proportion of the M. bovis-inoculated animals with no lesions. Correlation
      of antigen-induced IFN-gamma and IL-2 with other immune parameters suggests that
      these two cytokines play an important role in the immune response to bovine
      tuberculosis.

PMID- 9239840
TI  - Association of interleukin-6 in the cerebrospinal fluid during crisis of calf
      with ammoniated feed syndrome.
AB  - Ammoniated feed syndrome (AFS) in cattle is a neurotoxic syndrome caused by
      feeding specific ammoniated forage. To clarify the pathophysiology of AFS, we
      examined the association of interleukin-6 (IL-6) in the brain. By feeding milk
      either from cows fed such ammoniated forage or milk added with 4-methyl
      imidazole, newborn calves showed a neurotoxic crisis of hyperexcitability,
      ataxia, muscle tremor, circling, roaring, epileptoid seizure, sweating and marked
      fever response. Although these calves had no pathological lesions in the brain,
      we detected a rise in IL-6 in the cerebrospinal fluid (CSF). Tumor necrosis
      factor-alpha (TNF-alpha) was not detected in the CSF. In the sera, IL-6 and TNF
      alpha hardly changed during the experiment. Administration of recombinant human
      IL-6 into the lateral ventricle resulted in fever. Thus, we believe IL-6 in the
      CSF is related to the fever response in newborn calves with AFS.

PMID- 9239841
TI  - Isolation and phenotypic characterization of abomasal mucosal lymphocytes in the
      course of a primary Ostertagia ostertagi infection in calves.
AB  - Isolation and characterization of surface marker phenotypes of abomasal
      intraepithelial (IEL), lamina propria (LPL) and abomasal lymph node lymphocytes
      (ABLN) from uninfected calves were conducted, and the dynamics of change in these
      populations during the course of a primary Ostertagia ostertagi infection were
      defined. To obtain viable IEL and LPL from the abomasal mucosa of cattle, a
      modified isolation method was developed. The phenotypic characterization of
      abomasal lymphocytes was accomplished by indirect immunofluorescence staining. In
      uninfected animals, numbers of T cells exceeded the number of immunoglobulin
      bearing cells in IEL, LPL and ABLN. The predominant T cell type in IEL and LPL
      was CD8+ cells, while the CD4+ T cell predominated in ABLN. Levels of activated
      cells and T cell receptor-1 gamma delta T cells were higher in IEL and LPL
      compared to ABLN. Within 3 weeks of infection, the number of lymphocytes
      recovered from the abomasal lamina propira and the mass of the ABLN was
      dramatically increased when compared to uninfected animals. Laser flow cytometric
      analysis demonstrated increased levels of immunoglobulin-bearing cells, gamma
      delta T cells, and activated T cells in IEL, LPL and ABLN in the infected
      animals. The greatest changes in LPL and ABLN took place during the first days of
      infection, and these changes were apparent throughout the 28 days covered by the
      experiment.

PMID- 9239842
TI  - T-lymphocyte populations in the blood of caprine arthritis encephalitis virus
      infected goats.
AB  - The effect of natural infection by Caprine Arthritis Encephalitis Virus on the
      phenotypic pattern of T lymphocytes in peripheral blood was studied in a herd of
      127 milking goats by flow cytometry. Total leukocyte and T-lymphocyte numbers
      tend to decrease with age, with only small changes in the CD4/CD8 ratio. The
      lymphocyte phenotypes show no strong correlation with seropositivity to CAEV or
      the presence of clinical symptoms, suggesting that this macrophagetropic
      lentivirus does not greatly effect the lymphocyte population.

PMID- 9239843
TI  - Maturation of the mitogen responsiveness, and IL2 and IL6 production by neonatal
      swine leukocytes.
AB  - The maturation of the immune system of neonatal piglets was studied by following
      changes in the phenotypic composition and function of blood-borne leukocytes. The
      proportion of mature T and B lymphocytes decreased in the first week of birth and
      the circulating cells had poorly developed capacities to respond to mitogens and
      to secrete interleukins. From the end of the first week, however, there was a
      steady increase in the proportion of mature T cells (CD4+ and CD8+) and B cells
      in blood until 6-7 weeks after birth, when the study was ended. By 3-4 weeks, the
      relative proportions of different lymphocyte subsets resembled an adult-type
      composition. As they increased in prevalence, lymphocytes also developed
      capacities to proliferate and secrete interleukins. Proliferative responses to T
      cell and B-cell mitogens reached adult levels within 2 weeks and 4-5 weeks,
      respectively. Blood leukocytes produced large quantities of IL6 by 1-2 weeks
      after birth and IL2 by 2-3 weeks. In contrast to lymphocyte patterns, the myeloid
      and granulocyte lineages were dominant at birth but then declined steadily.
      Unlike lymphocytes, the monocytes, macrophages and granulocytes appeared to be
      fully functional from the time of birth and exhibited a strong oxidative burst
      after appropriate stimulations. The magnitude of this response remained constant
      over the first 6-7 weeks. These results indicate that the first 3-4 weeks of post
      natal life are a particularly susceptible interval for newborn piglets because
      constitutive and functional components necessary for specific cellular immune
      responses remain immature. This deficit may be offset by non-specific cellular
      mechanisms and maternally derived antibodies.

PMID- 9239844
TI  - Molecular cloning and mRNA expression of porcine interleukin-12.
AB  - Interleukin (IL)-12 is a heterodimeric cytokine consisting of 35 and 40 kDa
      subunits, produced primarily by phagocytic cells in response to bacteria or
      bacterial products. IL-12 is important in the regulation of both innate and
      antigen-specific immunity through its stimulatory effects on NK cells and
      cytotoxic lymphocytes. Reverse transcriptase-polymerase chain reaction with
      primers derived from human sequence was used to clone the p35 and p40 subunits of
      porcine IL-12. Predicted amino acid sequences for both subunits are approximately
      85% homologous to their human cognates but contain a 3aa addition and a 4aa
      deletion in p35 and p40 subunits, respectively. The high degree of similarity
      indicates the proteins may be cross reactive, an important consideration in pig
      human xenotransplantation. Both subunits of pIL-12 are constitutively expressed
      in a variety of porcine tissues. Highest levels of the p40 subunit were found in
      lymphoid tissues including inguinal and mesenteric lymph nodes, Peyer's patches,
      spleen and thymus. The p35 subunit was also detected in these tissues. Levels of
      mRNA encoding the p40 subunit, but not the p35 subunit, were rapidly increased in
      alveolar macrophages stimulated with lipopolysaccharide or killed Staphylococcus
      aureus. Thus, the heterodimeric subunits appear to be differentially regulated at
      the transcriptional level. Since p40 also self-associates to form inactive
      homodimers, differential expression may be a mechanism for regulating IL-12
      activity.

PMID- 9239845
TI  - Changes in classical pathway complement activity in dromedary camels
      experimentally infected with Trypanosoma evansi.
AB  - The complement system is known to have important effector functions in immune
      responses. However, its role in camel trypanosomosis has not been determined. The
      present study was undertaken to evaluate haemolytic complement activity in
      Trypanosoma evansi-infected and uninfected camels. Five dromedary camels were
      experimentally infected with T. evansi and classical pathway haemolytic
      complement activity was assayed. Parasitaemia and packed cell volume were also
      monitored. Following infection, classical pathway haemolytic complement showed a
      slight initial increase (7%) in all the camels. The amounts later dropped as the
      infection progressed and correlated negatively with parasitaemia. Haemolytic
      complement recovered following elimination of trypanosomes by treatment with
      melarsomine. Treatment of uninfected camels had no effect on complement. This
      study has demonstrated that complement concentration increases in the initial
      phase of infection followed by a drop as the infection progresses towards
      chronicity. In addition, the study has shown that activation of the classical
      complement pathway occurs in camels infected with T. evansi. Complement could
      therefore be involved in the in vivo control of parasitaemia in dromedary camels
      infected with T. evansi. Decreased complement levels in this species could lead
      to immunosuppression, widely reported in animal trypanosomosis.

PMID- 9239846
TI  - Development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens.
AB  - Chickens of the Obese strain (OS) are known to develop spontaneous autoimmune
      thyroiditis (SAT) in the first 2-3 weeks post-hatching, but onset and severity of
      SAT for this period among sublines of OS chickens has not yet been analysed in
      detail. In the present paper, we described the kinetics of SAT in age-matched
      OSB13B13C, OSB5B5C, OSB15B15INN and OSB5B5INN chicken sublines. The results
      revealed no thyroid infiltration in OS fetuses at 20th ED of the analysed
      sublines. Mononuclear cell infiltration of thyroid was first noted in 2-4-day-old
      chickens, followed by aggravation of thyroiditis in 4-week-old OSB13B13C and
      OSB15B15INN chickens and in 5-week-old OSB5B5C birds. Interestingly, two
      subpopulations of OSB5B5INN chickens were found with different kinetics of SAT
      development: one with degree of SAT lower than 40%, was designated "low
      responders" and the other, with similar degrees of SAT as the other three
      sublines, was characterized as "high responders". Our results allow an age
      dependent prediction of SAT development among OS chickens and the rational design
      of animal experiments, particularly for assessing the relevance of therapeutic
      interventions.

PMID- 9239847
TI  - Immunostimulating effect of growth hormone: in-vivo administration of growth
      hormone in rainbow trout enhances resistance to Vibrio anguillarum infection.
AB  - In-vivo administration of purified (nGH) and recombinant (rGH) chum salmon,
      Oncorhynchus keta, growth hormone enhanced the survival of rainbow trout, O.
      mykiss, against virulent Vibrio anguillarum. Macrophages obtained from rainbow
      trout that were treated in vivo with either GH preparation showed enhanced
      stimulation of the chemiluminescent responses induced by opsonized V. anguillarum
      cells and increased phagocytic activities. However, the serum bactericidal
      activity against V. anguillarum was not enhanced in fish injected with nGH or
      rGH. These findings show that in-vivo administration of either GH preparation can
      effectively prime macrophages and increase the resistance to V. anguillarum in
      rainbow trout.

PMID- 9239848
TI  - Studies on the effect of ethanol on the Na+, and the Na+, K(+)-ATPase activities
      of plasma membranes of rat kidney proximal tubular cells.
AB  - In the present work it was investigated the effect of 2% ethanol on the Na+ and
      on the Na+, K(+)-ATPase activities. The differential effect of the alcohol on the
      two ATPases (approximately 40% inhibition of the Na(+)-ATPase and approximately
      10% inhibition of the Na+, K(+)-ATPase), is not due to a higher degree of
      denaturalization of the enzyme, nor to a faster effect of ethanol on the Na(+)
      than on the Na+, K(+)-ATPase. Our results show that ethanol affects the
      selectivity of the Na+, K(+)-ATPase for Na+ and/or for K+, enhancing the Na+
      affinity for the K+ sites, and/or reducing the K+ affinity for its own sites.
      This effect was not seen for the Na(+)-ATPase, indicating that 2% ethanol
      inhibits the two ATPases in a totally different way.

PMID- 9239849
TI  - [Ecoepidemiology of Ascaris lumbricoides in an endemic area and its relation with
      blood groups].
AB  - 185 children 1 to 14 years old living in the suburb of San Rafael (Zulia State,
      Venezuela) were selected for this study with the following results: Eggs of
      Ascaris lumbricoides in the stool samples before administration of a drug to the
      children and the worms recovered after drug, induced expulsion, showed a high
      aggregation (K = 0.115 and K = 0.122, respectively); the aggregation of the
      recovered worms was more intense in girls (K = 0.083), than in boys (K = 0.220);
      among the blood groups, A. lumbricoides resulted highly prevalent (100%) and less
      overdispersed in group "AB" (K = 1.26; n = 5), while in the other blood groups
      the spatial aggregation pattern was strongly overdispersed (A = 0.159; B = 0.133
      and O = 0.210); individuals of the blood group "B", make the greatest
      contribution to environmental contamination, because they presented the greatest
      values for the abundance and a more intense overdispersion.

PMID- 9239850
TI  - [New interpretation of the quantitative fecal examination in humans].
AB  - The pattern of spatial disposition of eggs of the parasites (Ascaris
      lumbricoides, Trichuris trichiura and Ancylostomidae) into the faeces was found
      overdispersed, independently of the technique of coprodiagnosis used (Direct
      smear without standarisation, Stoll, Shore & Lynch, Kato-Katz and Mc Master).
      Therefore, differences were not detected in the interpretation of the results
      among the techniques at the population level, in quantitative studies. In an
      overdispersed pattern, only few hosts are the major responsibles for the
      environmental contamination. The importance of this spatial arrangement for
      parasite control purposes, is discussed.

PMID- 9239851
TI  - [Mosquito fauna (Diptera:Culicidae) from Falcon State, Venezuela. I. New records
      and current checklist].
AB  - A total of 16 new species records of Culicidae from Falcon State was collected at
      the "Juan Crisostomo Falcon National Park" (Sierra de San Luis), Natural Monument
      "Cerro Santa Ana", Coro, and La Vela. Species of Sabethini, Culicini and
      Toxorhynchitini Tribes were found in natural breeding sites (Phytotelmata), with
      special occurrence in plants belonging to Tillandsia, Vriesea, Guzmania, Aechmea
      (Bromelianceae), Heliconia (Heliconiaceae), Calathea (Marantaceae) and Colocasia
      (Araceae). Aedini and Mansonini were collected only as adults. A specie of Culex
      (Carrollia) was collected from an artificial container. The Culicidae species
      belong to 6 genera out of the 23 genera reported from Venezuela (Culex, Wyeomyia,
      Johnbelkinia, Aedes, Psorophora, Mansonia and Coquillettidia) and to 5 Tribes out
      of the 9 present in the country. The Aedini, Sabethini and Culicini Tribes were
      richer in species with 5, 4 and 4 species, respectively, than the Mansonini (2
      species) and Toxorhynchitini (1 species) Tribes. We discuss some bioecological
      aspects regarding the 16 new-species records in Falcon State and give a checklist
      of the mosquito species previously reported in the literature.

PMID- 9239852
TI  - [Toward a national system on science and technology].
AB  - This essay discuss the integration of a National System on Science and Technology
      (SINACYT), supported with resources arising from a National Found for Science and
      Technology (FONACYT), and whose leader entity should be the Institute of the
      National Found for Science and Technology (INFONACYT) to substitute CONICIT.

PMID- 9239853
TI  - [Tenth anniversary of chapter Falcon's: notes for the history of the Venezuelan
      Association for the Advancement of Science (AsoVAC)].
AB  - Chapter Falcon of the Venezuelan Association for the Advancement of Science
      (AsoVAC) was chartered in 1984. In this essay we outline and analyze the
      circumstances and elements that made possible the establishment of this chapter.
      The key factors probably were a tight relation with Universidad Nacional
      Experimental Francisco de Miranda (UNEFM), which allowed to advance several
      common projects; the selection of realistic projects that could be "read" as
      organizational muscle; setting of goals that could be achieved with the resources
      at hand; and taking advantage of some of the psychological traits of Falcon State
      inhabitants. This chapter's future is pondered under the light of the unusual
      responsibilities that it will face during this year: mainly the organization of
      the AsoVAC annual convention, which will be held in Falcon for the first time.

PMID- 9239854
TI  - Effect of vasoactive drugs on muscle fibre types and capillaries.
AB  - The effect of nitroglycerin, nifedipine, diltiazem or propranolol on fibre types
      and capillaries was studied in extensor digitorum longus (EDL) and soleus (S)
      muscles of the rat. In EDL muscle nifedipine increased the proportion of type I
      fibres (7.9% +/- 1.7 vs. 4.7% +/- 2.7). Nitroglycerin and dialtiazem decreased
      IIB fibres (40.7% +/- 10.6 and 37.3% +/- 14.6 respectively vs. 52.3% +/- 9.4).
      Propranolol increased IIB fibres to 66.3% +/- 8.1, while reducing IIA fibres
      (25.3% +/- 6.6 vs. 42.2% +/- 6.9). No changes in fibre type proportion were found
      in S muscle. Capillary density was increased in EDL by nitroglycerin (965 +/- 171
      vs. 818 +/- 98 cap/mm2). Propranolol had a dual effect on this parameter,
      decreasing it in EDL to 570 +/- 85 and augmenting it in S (754 +/- 117 vs. 601 +/
      121). No change was found in capillary to fibre ratio with any of the drugs
      either in EDL or S muscles. In EDL all the drugs except propranolol, which had
      the opposite effect, decreased the area of IIA fibre per capillary around 20%;
      this effect can be interpreted as a reduction of diffusion distance from blood to
      fibre.

PMID- 9239856
TI  - [XII Latin-American Congress of Microbiology and III Ecuadorian Congress of
      Microbiology].

PMID- 9239855
TI  - [The electrocardiogram of the guinea pig. Changes induced by beta-methyl digoxin
      acute administration].
AB  - In this study we describe the normal electrocardiogram of the Guinea pig (Cavia
      porcellus), including the correlation between cardiac frequency and the Q-T
      interval. We studied the acute changes induced by an intraperitoneal dose of beta
      methyl digoxin (0.2 mg). The drug produced a significant decrease in cardiac
      frequency and a significant prolongation of the P-R interval. It did not change
      the QRS duration or its position on the frontal plane. The Q-T interval,
      corrected by cardiac frequency, showed a tendency to decrease with treatment, but
      this change did not reach significance. The drug caused characteristic changes in
      ventricular repolarization: the T wave changed its polarity and S-T segment
      shifted to negative potential (between 0.05 and 0.15 mV). The possible origin of
      these observation is discussed.

PMID- 9239857
TI  - [XI Latin-American Congress of Genetics and III Latin-American Congress of
      Mutagenesis, Carcinogenesis and Environmental Teratogenesis].

PMID- 9239858
TI  - [Specific control of gene expression by oligonucleotides: from chemistry to
      clinical aspects].
AB  - Oligonucleotides can be synthesized for specific regulation of gene expression
      within the living cell. The oligonucleotide acts either on messenger RNA
      (nonsense and ribozyme strategies) or on DNA (triple helix or antigene strategy).
      This pharmacological approache requires chemically modified oligonucleotides and
      appropriate vectors. Applications in gene therapy can also be developed using a
      DNA vector to produce regulator RNA (nonsense, ribozyme, antigene) within the
      same cells. Early clinical trials are being conducted to determine the
      therapeutic efficacy of these two approaches.

PMID- 9239859
TI  - [Radioactivity serving health, one hundred years after Becquerel].

PMID- 9239860
TI  - [Modeling of cutaneous radio-contamination: effects of washings by soap and by
      solutions of DTPA].
AB  - Some neutral chirurgical soap, a solution of diethylen penta acetic acid (DTPA)
      at 1% and a solution at 25% of monocalcic trisodium salt of DTPA in serum have
      been studied on models of cutaneous contamination. Cesium 137 (137Cs) and
      Plutonium 239 (239Pu) have been used for the contamination. This research gives a
      protocol for external cutaneous decontamination which could be used in reception
      units for radiocontaminated wounded. Even the radioelement is unknown, DTPA at
      25% represents a good solution for the treatment of general contamination, which
      is not the case for DTPA at 1%. A soap in which DTPA at 1% has been added is
      adapted for large cutaneous contamination. The treatment of ocular contamination
      is also studied in this article.

PMID- 9239861
TI  - Topological structure activity analysis of diphosphonates in the elimination of
      radionuclides from body.
AB  - The effectiveness of a series of diphosphonates in the elimination of
      radionuclides from rat was analyzed by means of topological structure and
      activity relations. It is possible to compute some numbers or indexes
      characteristic of the topological structure of a molecule. The Wiener Index which
      measures the ramification of a molecule has been chosen. An attempt was made to
      correlate the effectiveness of the molecules tested in removing plutonium from
      the organism to their Wiener Index. Only unprotected molecules i.e in free acidic
      form fitted the correlation. LICAM (C) and DTPA were used as reference molecules
      to control these results. The fact that LICAM (C) well fitted the relation and
      that DTPA did not are discussed, as are some general requirements for a new
      molecule to be effective.

PMID- 9239862
TI  - [Synthesis of peptide and pseudo-peptide analogs of cholecystokinin].
AB  - We describe selective CCKA receptor antagonists, based on the 1-oxo-1,2,3,4
      tetrahydro-beta-carboline-3-carboxylic acid core. Selectivity A vs B is discussed
      on the basis of molecular modelling. Chemical preparation uses electrophilic
      cyclization of isocyanates derivating from unnatural tryptophan esters. A
      stereoselective version of the reaction is given. A few peptides incorporating
      unnatural tryptophans are prepared, with a view of SAR.

PMID- 9239863
TI  - [The history of blood pressure determination. 100 years of the sphygmomanometer].

PMID- 9239864
TI  - [Ventricular dysfunction. The importance of early diagnosis].

PMID- 9239865
TI  - [The challenge of secondary prophylaxis in rheumatic fever].

PMID- 9239866
TI  - [Blood pressure assessment in normoreactive and hyperreactive patients. A
      comparative study between casual and ambulatory blood pressure monitoring].
AB  - PURPOSE: To evaluate the levels of blood pressure when measured by casual and
      ambulatory blood pressure monitoring. METHODS: We studied 16 sedentary and
      normotensive subjects (mean 43 +/- 3 years old) showing an exaggerated blood
      pressure response (SBP > 220 mmHg) during a cycloergometric test, hyperreactive
      group (HG). This group was compared to 15 others with SBP < or = 220 mmHg during
      exercise, normoreactive group (NG). Casual blood pressure was obtained by the
      conventional method and the ambulatory blood pressure monitoring (ABPM) was
      obtained with SpaceLabs 90207 monitor. This procedure (test 1) was repeated after
      four months (test 2). RESULTS: Both groups showed statistically higher levels of
      blood pressure when measured by ABPM device, compared to casual measurements.
      Systolic blood pressure was significantly higher in HG in casual measurement, in
      test 1 but not in test 2. Diastolic blood pressure was significantly higher in HG
      only through the ABPM device. The ambulatory blood pressure average values for
      two or 24 hours was similar in both groups. No significant differences were
      observed in left ventricular morphology at the echocardiogram. CONCLUSION: These
      findings indicate that hyperreactive subjects have an exaggerated stress-induced
      cardiovascular response during the installation of the device.

PMID- 9239867
TI  - [Effects of age, sex and coronary heart disease on the autonomic modulation of
      the heart].
AB  - PURPOSE: To establish the influence of age, sex and the presence of coronary
      heart disease on heart rate variability. METHODS: The heart rate variability was
      studied in the time and frequency domain in 77 normal (group I) and 30 coronary
      heart disease patients (group II). The ECG was recorded during 300 seconds with
      the patients breathing at their spontaneous rate and at a rate between 10 and 15/
      minutes (0.16 to 0.25 Hz). RESULTS: Both time and frequency domain variables were
      lower in group II than in group I. Energy content in spectral bands decreased
      with increasing age. No change was observed in relation to the patient's gender.
      During controlled breathing we found that in both groups the energy concentrated
      in the range of 0.17 to 0.25 Hz but it only increased in group I. CONCLUSION:
      Heart rate variability is an important tool for studying the influence of the
      autonomic system on heart rate modulation. These influences decrease with age and
      with the presence of coronary heart disease. The controlled breathing maneuver
      enabled us to precisely separate normal from coronary heart disease patients.

PMID- 9239868
TI  - [Secondary prophylaxis in rheumatic fever. Oral antibiotic therapy versus
      benzathine penicillin].
AB  - PURPOSE: To detect problems related to secondary prophylaxis of rheumatic fever
      in the setting out patient follow-up. METHODS: Among 113 pediatric patients
      admitted with diagnosis of this disease, in a period of five years, we selected
      80 records. They were divided in group 1 (60 cases), that only received
      prescription of benzathine penicillin for prophylaxis and group 2 (20 patients)
      to whom it was changed from parenteral to oral antibiotics after the detection
      problems using the first scheme. RESULTS: In group 1, among 53 who had carditis,
      27 (45%) had severe disease; 22 cases (37%) were re-admitted with relapsed
      carditis following the refusal to use benzathine penicillin. Also, we observed
      that after discharged 32 (55%) did not return to the out-patient clinic in HUAP.
      In group 2, from 16 who had carditis, 10 (50%) had severe disease. Only two (10%)
      did not return to ambulatory control and there was no case of readmission. The
      difference between the groups was statistically significant. (p < 0.01).
      CONCLUSION: It was very high the percentage of cases that missed the control
      visits and abandoned the prophylaxis when it was insisted on parenteral
      penicillin. We should evaluate every case and remember that oral antibiotics
      might avoid a major problem.

PMID- 9239869
TI  - [Thoracic pain and early repolarization syndrome at the cardiologic emergency
      unit].
AB  - PURPOSE: To analyze the clinical and electrocardiographic characteristics of
      early repolarization syndrome (EP) in patients with thoracic pain. METHODS:
      Patients with thoracic pain and early repolarization were studied. EP was
      diagnosed on the basis of the presence of two or more criteria: ST elevation;
      upward concavity; notch or slur on QRS; assymetrical T waves of large amplitude;
      U waves. RESULTS: Of 350 patients treated in the emergency department, 17 were
      studied. Sixteen were men, mean age 43.9 years. Four were black. The thoracic
      pain was atypical in 15. All the patients had ST elevation with upward concavity,
      most frequently in leads V2. Tall, peaked, positive waves were found in nine
      patients and U waves were present in 14. CONCLUSION: The electrocardiographic
      characteristics of ST elevation with upward concavity most frequently observed in
      precordial leads in patients with atypical precordial pain are important to
      establish a differential diagnosis, to be confirmed by previous electrocardiogram
      and cardiac enzymes.

PMID- 9239870
TI  - [When should we stop cardiopulmonary resuscitation in patients brought to the
      emergency room in cardiac arrest without pre-hospital care?].
AB  - PURPOSE: The decision of stopping cardiopulmonary resuscitation (CPR) in patients
      brought to emergency room in arrest remains a challenge. Such decision is even
      more difficult when someone is brought by bystanders, after an acute loss of
      consciousness without any out-of-hospital care. To evaluate the probability of
      survival of these patients we reviewed retrospectively charts in our institution,
      during a period of five years. METHODS: One hundred and one patients that
      fulfilled these characteristics came to our emergency in arrest. The time to
      arrival since symptoms started, cardiac rhythm at first electrocardiogram (EKG),
      age, gender, initial CPR success, late outcomes and previous diseases were
      obtained. Patients were divided in two groups regarding which cardiac rhythms
      they had at first EKG: A-patients arriving in asystole; and VF-patients arriving
      in ventricular fibrillation. To evaluate time to arrival, we arbitrarily choose
      15 min as a reference point. RESULTS: In these 101 subjects the mean age was 62
      +/- 13.7 years and 63 (62.3%) were men. Previous heart disease was documented in
      74 [dilated cardiomyopathy in 22 (21.7%), coronary heart disease in 41 (40.6%),
      arterial hypertension in 25 (24.7%) and others in 6 (5.6%)]. In 66 episodes we
      were sure of the time patients spent before arrival (mean 2.5 +/- 11 min). Only
      in 63 subjects we had no doubts about the rhythm at entrance: VF in 37 (58.7%), A
      in 22 (34.9%) and an accelerated idioventricular rhythm (AIR) in four (6.3%).
      Time to arrival was 18.6 +/- 10.6 in VF vs 32.5 +/- 11.7 min in A (p = 0.012).
      Fourteen (13.8%) subjects resumed a supraventricular rhythm with systolic
      pressure > or = 90 mmHg after CPR and all of them were in VF (13) or AIR (one).
      Nine patients (8.9%) evolved in coma. Only five (4.9%) were discharged from the
      hospital without any neurological disturbance and their time to arrival ranged
      from one to 15 (9 +/- 5.8) min. CONCLUSION: Delayed arrival to the emergency room
      (> 15 min) associated with asystole were predictors of unsuccessful CPR, and both
      data are helpful in deciding when to stop CPR in subjects arriving at the
      emergency department with no out-of-hospital care.

PMID- 9239871
TI  - [Use of the Palmaz-Schatz stent in the acute phase of myocardial infarction in a
      patient with cardiogenic shock].
AB  - A 56-year-old female patient underwent myocardial revascularization with three
      saphenous bypass grafts. One month after surgery she had an acute myocardial
      infarction with cardiogenic shock and was treated with a Palmaz-Schatz stent
      implantation in the left main coronary artery (that was occluded) and a PTCA of
      the graft to the right coronary artery. The in hospital outcome was uneventful
      and angiographic study after six months showed no restenosis and important
      improvement in the left ventricular function.

PMID- 9239872
TI  - [Myxoma of the left atrium causing acute myocardial infarction].
AB  - A 66-year-old male patient had an acute inferior wall myocardial infarction 55
      days prior to the admission to the hospital. Echocardiogram and cardiac
      catheterization disclosed a tumor of the left atrium and the coronary
      arteriography was normal. The tumor was surgically removed and pathological
      examination revealed it to be a myxoma. In the absence of other etiologic
      possibilities, left atrial myxoma was considered the main hypothesis with the
      development of thrombi and coronary embolization.

PMID- 9239874
TI  - [Neonatal heart failure and Marfan syndrome].
AB  - We report the case of a neonate admitted to the hospital in the 4th day of life
      in severe heart failure due to aortic and mitral regurgitation with a largely
      dilated aortic root. The associated skeletal features involving the superior and
      inferior limbs as well as the thorax, and joint hypermobility, allowed the
      clinical diagnosis of Marfan syndrome. Despite favorable initial response to
      medical therapy, sudden deterioration led to death two weeks after birth. Typical
      necroscopic findings were confirmed and the case is considered the most severe
      clinical manifestation possible to be found in this syndrome.

PMID- 9239873
TI  - [Mitral subvalvular aneurysm of the left ventricle].
AB  - A 21-year-old white man presented with cardiogenic shock and refractory pulmonary
      congestion. At the transthoracic echocardiogram a subvalvar left ventricular
      aneurysm of the inferior wall with severe mitral regurgitation was observed. The
      outcome was favorable after surgical correction of the mitral regurgitation and
      of the subvalvar aneurysm. We emphasize that, whenever possible, valvar repair is
      better than mitral replacement, since annulus tissue fragility causes suturing of
      the mitral prosthesis to be difficult.

PMID- 9239875
TI  - [Anatomo-clinical correlation. Case 4/96 (Instituto do Coracao do Hospital das
      Clinicas--FMUSP].

PMID- 9239877
TI  - [Anatomo-clinical correlation. Case 2/96].

PMID- 9239878
TI  - [Tc-99-sestamibi scan in the preoperative localization of abnormal
      hyperfunctioning parathyroid glands].
AB  - Hyperparathyroidism is a relatively frequent condition mostly due to a solitary
      parathyroid adenoma. Although it has been claimed that surgical exploration is
      the best way to visualize the abnormal parathyroid gland, several imaging
      techniques have been proposed to localize it in order to simplify and shorten the
      surgical procedure. Echography, thalium-technetium scintigraphy, computerized
      tomography and nuclear magnetic resonance have shown a mean sensitivity of 75%
      which can be increased to about 90% by combining 2 or more of these procedures.
      In this study, we evaluated the utility of Tc-99m-sestamibi scintigraphy in 13
      patients with hyperparathyroidism (11 primary, 2 secondary). High resolution neck
      echography was carried out in all of the cases. Cervical scans were obtained 10
      15 min and 3 hours after giving an i.v. injection of 25 mCi Tc-99m-sestamibi in
      all the patients; suppression studies with combined 131-I were also done.
      Positive scans were obtained in 11 out of the 13 patients. Abnormal parathyroid
      glands were found and surgically excised in all the cases (10 adenomas, 1
      carcinoma, 2 hyperplasias). Echographic localization had a sensitivity of only
      33.3%. On the contrary, Tc-99m-sestamibi showed a sensitivity of 56% for the
      whole group, increasing to 82% in the 11 patients with primary
      hyperparathyroidism whereas the positive predictive value was of 91% and 90%,
      respectively. We conclude that Tc-99m-sestamibi is a very useful tool in
      localizing abnormal parathyroid glands and should be the first choice before
      reoperation after surgical failure or before the first parathyroid surgery
      whenever it is desired to shorten the surgical and anesthetic duration.

PMID- 9239879
TI  - [Iodine in school children. Relationship with incidence of goiter, socioeconomic
      group and salt intake].
AB  - In order to evaluate iodine daily intake in 5-14 year-old school children urinary
      iodine excretion was measured in morning urinary samples of 134 school children.
      This value was corrected to microgram/ 24 h according to Jolin and Escobar del
      Rey's formula. Thyroid size was evaluated by two expert examiners following WHO
      criteria. Coincidence between both examiners was indispensable to establish
      goiter diagnosis. We evaluated urinary samples of 134 school children (117 normal
      and 17 goitrous). Urinary iodine excretion mean values were significantly
      different between Normal: 140.04 +/- 86.28 micrograms/24 h and Goitrous: 98.24 +/
      47.91 micrograms 24 h; p < 0.005). Goiter prevalence was found to diminish
      significantly when urinary iodine excretion was greater than 150 micrograms/24 h
      (p < 0.05). Similar mean urinary iodine excretion was observed in different
      socioeconomic groups. No significant differences were detected in the evaluation
      of two most common salt trademark consumer groups. In conclusion 1)
      iodoprophylaxis efficacy was assessed by urinary iodine excretion, a valid means
      to estimate iodine intake. Acceptable mean levels of iodine intake were found in
      the group under study, but the individual variability was important; 2) goitrous
      schoolchildren showed an iodine intake lower than normal and 3) the important
      variability observed in the evaluated data, the assessed relation between goiter
      and lower iodine intake, and the high frequency of insufficient iodine intake
      should justify a better control of iodoprophylaxis and a more widespread
      information dissemination among the population and perhaps iodine supplements in
      specific groups.

PMID- 9239880
TI  - [Night suppression with high doses of dexamethasone and metyrapone tests for the
      etiological diagnosis of Cushing syndrome].
AB  - Different approaches are used to determine the cause of Cushing's syndrome (CS).
      In this study we evaluated the validity of nocturnal high dose dexamethasone and
      metyrapone tests in patients with CS of different etiology. A total of 61
      patients (51 women, 10 men), aged 13-61, were studied. Definitive etiological
      diagnosis was established on imaging, surgical and pathological findings, and/ or
      the clinical evolution after treatment. On that basis, the patients were
      classified as follows: 41 with Cushing's disease, 16 with adrenal tumors (11
      adenomas and 5 carcinomas) and 4 with ectopic CS. Nocturnal dexamethasone (8 mg)
      test was carried out in all the patients; in 43 out of the 61 patients, 11
      deoxicortisol responses to metyrapone were also determined. The sensitivity,
      specificity, accuracy and positive predictive power for the diagnosis of
      pituitary CS were calculated for both tests. For the nocturnal dexamethasone
      test, values were 85, 100, 90 and 100%, respectively (n = 61); the sensitivity
      and specificity increased to 95 and 97% by repeating the test in six false
      negative patients. Results for the metyrapone test were 90, 85, 88 and 93%,
      respectively (n = 43). When both tests were considered together, the values were
      97, 100, 98 and 100% higher, although not significantly, than those for each
      separate test (n = 43). In conclusion, we believe that the combination of
      metyrapone and nocturnal high dose dexamethasone tests carried out on an
      outpatient basis has enough sensitivity, specificity, diagnostic accuracy and
      positive predictive value to be employed as an easy and low cost strategy in the
      etiological diagnosis of CS.

PMID- 9239881
TI  - [Clinical and spirometric alterations in patients with Duchenne muscular
      dystrophy].
AB  - In 36 patients with Duchenne muscular dystrophy we studied the growth pattern,
      the type and severity of the spirometric abnormalities, the evolution of the
      Motor Functional Class (MFC), the infectious complications and treatments. Their
      age ranged from 6 to 19 years and the MFC was from 1 to 9. Regarding height, up
      to 12 years we verified a slope of 5.69 +/- 0.58 cm/year (r 0.872 p < 0.001) and
      a posterior detention was observed. Of the 36 patients, 24 were below the
      percentile 5. The restrictive disorder prevailed. The forced vital capacity (FVC)
      expressed in % of the theoretical value showed a lineal fall with age, with a
      negative correlation (r 0.51, p < 0.01) of -3.5 +/- 0.83%/year. The deterioration
      of the MFC was marked starting from 6 years; with a slope of 0.84 +/- 0.14 points
      between 6 to 12 years (r 0.73 p x 0.001). Up to 14 years, the slope was 0.212 +/-
      0.084 (r 0.49, p < 0.05). Patients older than 14 years had reached a greater CFM
      of 7; starting from this MFC a progressive fall of the VC was observed with a
      slope of -15.29 +/- 3.39% of CVF/CF (r 0.56, p < 0.001). Nine patients with
      respiratory infections were documented. Four were pneumonia and 3 of them
      required mechanical ventilation and died. Only 50% of the patients accepted
      rehabilitating treatment. Four patients accepted surgery of the alterations of
      the feet while the patients with deformation of the column underwent spinal
      stabilization.

PMID- 9239882
TI  - [Acute effect of lorazepam on respiratory muscles in stable patients with chronic
      obstructive pulmonary disease].
AB  - Benzodiazepines are known to cause muscle hypotonia, but their effects on
      respiratory muscle function, particularly on diaphragm, have not yet been
      studied. Our aim was to look for any effect of lorazepam on respiratory muscle
      function in patients with chronic obstructive pulmonary disease (COPD). Nine
      stable COPD patients (mean +/- SD forced expiratory volume in one second (FEV1)
      0.91 +/- 0.31 l) were included in the study. The following measurements were
      performed before and 1 hour after lorazepam administration (doses: 1.5 to 2 mg)
      by sublingual route: forced vital capacity (FVC), FEV1, maximal voluntary
      ventilation (MVV), arterial oxygen tension (PaO2), arterial carbon dioxide
      tension (PaCO2), minute ventilation (Ve), tidal volume (Vt), respiratory rate
      (f), inspiratory time/inspiratory plus expiratory time (Ti/Ttot)-, mean
      inspiratory flow (Vi), maximal inspiratory (MIP) and expiratory (MEP) pressures,
      maximal pleural pressure (Pplmax), transdiaphragmatic pressures (Pdi) and
      skeletal muscle strength and endurance. As expected, no change was noted in FVC,
      FEV1, FEV1/FVC (Table-1). Besides stability of expiratory flows, this denotes no
      change in collaboration in spite of the sedative effects of lorazepam. There was
      a 20% decrease in Ve, due to a Vt reduction and a small increase in PaCO2. These
      could be explained by the central effects of benzodiazepines. Skeletal muscle
      strength and endurance decreased significantly (22 and 50% respectively-Table 2),
      in accordance with the previously reported muscular actions of this
      pharmacological group. Respiratory muscle function parameters, MIP, MEP, MVV and
      Ppl showed significant reductions (10 to 20 per cent), as was the case with
      diaphragmatic function measured by Pdi (Muller maneuver with abdominal
      protrussion and maximal open-glottis expulsive maneuver) (Table 3). This study
      demonstrates that a single lorazepam dose reduces strength and endurance of
      respiratory muscle in chronic stable COPD patients.

PMID- 9239883
TI  - [Very low density lipoproteins and subclasses of intermediate density
      lipoproteins in postmenopausal women].
AB  - Post menopausal women present an increase of cardiovascular risk associated with
      the atherogenic plasma lipoproteins IDL and LDL. Our purpose was to study the
      composition of VLDL, IDL and the subfractions IDL-1 and IDL-2, and the
      Lipoprotein Lipase and Hepatic Lipase activities in a group of twelve healthy
      post menopausal women as compared with eleven fertile controls. The mean values
      of total cholesterol and LDL cholesterol were significantly increased in the post
      menopausal group compared to the controls (p < 0.005 and p < 0.001 respectively).
      The contribution of the HDL-cholesterol plasma concentration to total cholesterol
      was lower in the postmenopausal women (p < 0.02) although no one had HDL
      cholesterol lower than 35 mg/dl and the mean value was 50 mg/dl. Postmenopausal
      women had increased concentrations of VLDL, total IDL and IDL-2 compared to
      controls (p < 0.05, p < 0.005 and p < 0.001 respectively). Plasma concentrations
      of total IDL was increased in postmenopausal women (33.6 +/- 3.4 vs 22.6 +/- 0.8
      mg/dl, p < 0.005). The increase in total IDL was due to IDL-2 (19.9 +/- 1.7 vs
      11.5 +/- 0.8 mg/dl, p < 0.001, in postmenopausal women vs controls). The IDL-2
      subfraction was 60 +/- 2.6% of total IDL in postmenopausal women and 51 +/- 2.0%
      in controls (p < 0.02). In postmenopausal women and in controls the ratio
      triglyceride/protein (which indicates particles size) was significantly higher in
      IDL-1 than in IDL-2 (p < 0.005 and p < 0.01 respectively), but this ratio did not
      show differences when VLDL, total IDL and IDL-2 were compared between
      postmenopausal and control women. Then, the increased plasma concentration of
      these lipoproteins would show an increased number of particles in the
      postmenopausal women vs controls. There were no differences in the Lipoprotein
      Lipase and Hepatic Lipase activities between both groups. Lipoprotein Lipase vs
      total IDL-triglycerides and IDL-2-triglycerides showed a significant inverse
      correlation in controls (p < 0.05) but not in postmenopausal women. We conclude
      that the qualitative and quantitative study of the lipoproteins shows a more
      atherogenic profile in the postmenopausal group, with an increase in the
      concentration and number of particles of VLDL, total IDL and IDL-2.

PMID- 9239884
TI  - [Participation of Campylobacter jejuni flagellar epitopes in cellular adhesion].
AB  - Using a flagellated (052) and an aflagellated (T-1) strains we studied the
      participation of flagellar epitopes of C. jejuni in the adhesion to HEp-2 cells
      in vitro. Strain 052 was significantly more adherent than strain T-1. When
      adhesion assays were carried out with antiflagella monoclonal antibodies, strain
      052 showed inhibition of their adhesive capacity that varied between 64.3 and
      92.9%. With an ELISA test it was demonstrated that those monoclonal antibodies
      were specific and directed exclusively against flagellar epitopes of strain 052
      being unreactive with strain T-1. Our results show that flagellar epitopes could
      participate in the adhesion process suggesting that flagella could be involved in
      the installation of the infectious process.

PMID- 9239885
TI  - [Hepatic artery aneurysm].
AB  - We report the case of a 45-year old man who presented a common hepatic artery
      aneurysm. He had alcoholic habits and after an episode of upper gastrointestinal
      tract bleeding underwent an abdominal ultrasound study. This showed a large fluid
      filled upper abdominal mass related to the pancreatic head. Both T scan and an
      angiogram showed an hepatic artery aneurysm. It was resected and the artery
      repaired interposing a saphenous vein graft. The patient was discharged a week
      after surgery. Most of the hepatic artery aneurysms are free of symptoms and
      difficult to palpate and only a few patients can be operated before the
      occurrence of aneurysmal fissure. Broad use of ultrasound and selective
      angiography has increased the number of cases diagnosed before complications,
      reducing the mortality rate, which, in the past, has been reported up to 59%.

PMID- 9239886
TI  - [Anatomoclinical meeting: polyneuritis, hepato-splenomegaly, hypothyroidism and
      Raynaud's disease].

PMID- 9239887
TI  - [Molecular genetics of hemophilia A].
AB  - Hemophilia A (HemA), an X linked genetic disease, is the most common coagulation
      disorder with an incidence of about 1-2 in 10,000 males and is caused by
      mutations in the factor VIII (FVIII) coagulation gene. Firstly, some clinical
      aspects of the HemA are presented: the current methods to assess both the amount
      and activity of FVIII, the severity range observed and the presence of inhibitor
      antibodies against the therapeutic FVIII. Follows a discussion of the
      relationship of the structural domains of the FVIII protein (Figure 1), the
      aminoacid sequence and their functions. An activation-inactivation model of the
      successive peptide bonds cleavages of the FVIII is also presented (Figure 2).
      After the cloning of the FVIII gene in 1984, almost all types of HemA causing
      mutations have been characterized. However, the size and complexity of this gene
      prevented a screening of the full range of mutations for an accurate molecular
      diagnosis. Moreover, most of the patients with moderate and mild disease have
      missense mutations whereas approximately half of severe patients have nonsense,
      frameshift, and some missense mutations. There are also less frequently mutations
      such as deletions and insertions leading to severe phenotype and mutations
      affecting mRNA splicing and duplications causing both severe and mild HemA. In
      order to give genetic counselling in HemA families, studies at the DNA level
      using intragenic and/ or extragenic polymorphism analysis have been used. But
      this approach is not entirely satisfactory because it fails in several
      situations. Most of the causing mutations described above are private, and they
      have been found in only a few unrelated families. Recently, a common molecular
      inversion of the FVIII gene was identified in 50% of unrelated patients with
      severe HemA. The copies of a particular DNA sequence (termed F8A gene). One copy
      is located within intron 22 of the FVIII gene and the other two, 500 kb upstream.
      An homologous recombination mechanism was proposed for the inversion between an
      intragenic copy of the F8A gene and either the distal (80% of the inversion) or
      the proximal copy (20%). Both of these inversions lead to severe HemA because no
      intact FVIII is produced and can be easily diagnosed by Southern blot analysis.
      This inversion originates almost exclusively in male germ cells, because pairing
      Xq with its homologous in female meiosis would probably inhibit the proposed
      intrachromosome recombination. The molecular analysis of the inversion of intron
      22 is now considered as the first line for families with severe HemA patients. In
      recent years the treatment of patients with hemophilia A and B has been
      intravenous injection of FVIII or FIX concentrates, respectively. This regimen of
      regular injection of plasmatic proteins bears a high risk of infection by
      contaminating viruses (HIV, HBV, etc). Future treatment for patients with
      hemophilia may include the use of either gene therapy or recombinant coagulation
      factors. Both strategies would completely avoid the infection risk offering a
      safe and effective treatment for the disease. Recombinant factors, obtained by
      genetic engineering methods, provide a renewable and unlimited source of FVIII or
      FIX. The clinical trials of recombinant factors have already started in mid-1995
      giving positive results. On the other hand, gene therapy for hemophilia is now in
      the pre-clinical stage but offers the prospect of a cure for the disease, thus
      potentially freeing patients from regular injections of the lacking protein.
      However, experiments in animal models suggest that it may be difficult to obtain
      adequate therapeutic levels of factors for long periods of time. Recently, a
      retroviral-mediated gene delivery of human FVIII in mice has been reported using
      the ex vivo strategy of gene therapy. Therapeutic levels of FVIII in the
      circulation were obtained for > 1 week and it was also observed that the capacity
      of primary cells to deliver FVIII in blood was strongly dependent on

PMID- 9239888
TI  - [Insulin, vascular reactivity and hypertension].
AB  - Several epidemiological studies have shown that there is a relationship between
      hyperinsulinemia, insulin resistance and arterial hypertension. Insulin produces
      sympathetic nervous system stimulation, enhances renal sodium retention and it
      directly modifies vascular mechanisms involved in both contraction and relaxation
      of the vascular smooth muscle. These actions of insulin could lead either to
      elevation or reduction of blood pressure. The absence of vasodilation due to
      insulin resistance and/or the enhancement of the hypertensive effects due to
      hyperinsulinemia could be the link between insulin and hypertension.

PMID- 9239889
TI  - [XI International Conference on AIDS in Vancouver].

PMID- 9239890
TI  - [More about Helicobacter pylori or less?].

PMID- 9239891
TI  - [Ethics in the use of experimental animals].

PMID- 9239893
TI  - [Evaluation of the possible influence of Montenegro's intradermal reaction on a
      serological assay for the diagnosis of American cutaneous leishmaniasis].
AB  - Influence of Montenegro skin test for American tegumentar leishmaniasis was
      evaluated to verify possible interference in serological diagnosis for this
      disease, performed by immunoenzymatic assay (ELISA). If this interference could
      occur, it would hamper scientific, epidemiological and patient care; happily we
      did not find any interference on serological diagnosis by performance of skin
      testing.

PMID- 9239892
TI  - [Treatment of hair cell leukemia with 2-chlorodeoxyadenosine and G-CSF].

PMID- 9239894
TI  - [Blepharospasm: treatment with botulinum toxin].
AB  - Blepharospasm is form of focal dystonia characterized by involuntary and
      repetitive contractions involving the orbicular oculi muscle. Fourteen patients
      with blepharospasm were submitted to botulinum toxin type A injections. Of these
      14 cases, 6 were male and 8 female. The mean age was 58 years (range: 33 to 76
      years) with illness duration ranging from 1 to 25 years (average: 7.3 years). All
      patients have been treated with conventional therapies with poor results, but
      presented a good response to botulinum toxin type A. The average latent period
      was 3 days (range: 0 to 10); maximum effect of treatment was observed after 16
      days. The mean duration of maximum response was 90 days. The main side effects of
      botulinum toxin injections were ptosis and lagophtalmos.

PMID- 9239895
TI  - [Comparative study of the coronary circulation pattern of anatomic specimens and
      surgical patients].
AB  - The recent improvement in the cardiac surgery requires a continuous study of the
      great anatomy of the heart. In this paper, we compare the anatomic pattern of the
      coronary artery between normal individuals and individuals with sintomatic
      ischemic disease of the heart. The anatomic pattern of circulation was carried
      out in two different groups: group I formed by 119 anatomical specimens taken
      from individuals whose cause of death was non-cardiac and group II formed by 150
      live individuals with sintomatic coronary disease, on pre-operative management.
      In the former was performed epicardiectomy and in the latter, radiologic study.
      In group I was found 68% of right predominance, 13% of left predominance and 19%
      of balanced type of circulation. In group II was found 59%, 17% and 24%,
      respectively. When considering the number of branches that trespass the crux
      cordis in group I, there was 48% with only one branch, 28% with two, 17% with
      three, 4% with four and 3% with five branches. Performing the same study for
      group II, we found 47%, 29%, 14.6%, 3.4% and 6% respectively. Both groups were
      compared by Chi-square test and by Fisher's Exact test and no considerable
      difference was pointed out.

PMID- 9239896
TI  - [Hepatic dysfunction in myoglobinuric acute renal failure (rhabdomyolysis)-
      experimental study in rats].
AB  - Liver damage as a consequence of rhabdomyolysis (RM) has not been well
      established on clinical and experimental grounds. Hepatic dysfunction was then
      investigated in rats 24 h after induction of acute renal failure with glycerol.
      Forty male Wistar rats (220-270 g) were dehydrated for 24 h and were divided in
      two group: GI experimental group (n = 14)-50% glycerol was injected (10 ml/Kg,
      one-half of the dose in each hindlimb muscle) and GII control group (n = 26)
      animals received injection of saline solution. Twenty-four hours after the
      glycerol or saline injection all the animals were killed. Serum urea, creatinine,
      transaminases (AST, ALT) and CK were measured and significantly high values were
      obtained in experimental animals. Arterial blood pressure was measured and
      remained within normal levels in both groups. Hepatocyte mitochondrial
      respiratory function was estimated polarographically with determination of oxygen
      consumption without ADP (Basal respiration-State 4) and in the presence of ADP
      (Activated respiration-State 3). In experimental group (GI) there was significant
      low values of oxygen consumption in state 3, decrease of respiratory control rate
      and in ADP/O ratio (p < 0.05). Histological studies of the liver revealed a
      periportal necrosis and centrilobular degeneration. These studies suggested that
      hepatic dysfunction is an additional complication of glycerol-induced
      rhabdomyolysis. The pathogenesis and clinical implications of these abnormalities
      are discussed.

PMID- 9239897
TI  - [Physiopathology of lung injury in acute pancreatitis].
AB  - Clinically detectable signs of lung injury develop in up to 50-70 percent of
      patients with acute pancreatitis. Despite that, the physiopathology of the lung
      injury associated with acute pancreatitis is unclear so far. Pulmonary edema is
      the main respiratory complication in acute pancreatitis. Increased permeabilities
      of the pulmonary endothelial and alveolar epithelial barriers are the causes of
      the pulmonary edema. Several factors have been regarded as the cause to pulmonary
      edema: release of pancreatic-derived proteolytic enzymes, oxygen-free radicals,
      phospholipase A2, free fat acids, tumor necrosis factor, platelet activating
      factor, arachidonic acid metabolites and pulmonary embolization. Understanding
      lung injury physiopathology enables physicians to a better therapeutic approach
      of the patients with acute pancreatitis. The aim of this paper is to expose the
      theories that explain the pancreatic-derived lung injury.

PMID- 9239898
TI  - [Evaluation of normal thoracic and abdominal aortic diameters through
      computerized tomography].
AB  - We measured the widest anteroposterior diameters of the thoracic and abdominal
      aortas of 350 patients without cardiovascular diseases who had undergone
      computerized tomography of the thorax and/or abdomen. After classifying them
      according to gender and age group, we calculated the mean diameters and standard
      deviations, and determined the ratios between the ascendant and descendent
      thoracic aortic diameters, and of the abdominal aorta, concluding that: both the
      thoracic and abdominal aortic diameters are reduced from their proximal to their
      distal portions; the body surface influences the size of the aorta; vessel
      diameters was observed to gradually increase with age; men were found to have
      larger diameters than age matched women; the ratio between the ascending and
      descending aortic diameters varies according to gender and age; the relations
      between abdominal aortic diameters measured at the level of renal hila and
      cephalad to the bifurcation areindepend from gender and age; but, the relation
      between those measured at the level of the superior mesenteric artery and
      cephalad to the bifurcation are linked to gender, but not to age.

PMID- 9239899
TI  - [Traumatic rupture of duodenal diverticulum. Report of a case and literature
      review].
AB  - Duodenal diverticulum is a common anatomic abnormality. Its inflammatory
      perforation is a rare complication, with less than 100 cases reported in the
      available literature. Traumatic perforation is exceedingly rare (only 3 cases
      reported). In this report one more case of traumatic perforation is presented,
      and the literature is reviewed focusing on the pathogenic, diagnostic and
      therapeutic aspects of this severe disease.

PMID- 9239900
TI  - [Iatrogenic diaphragmatic hernia following abdominal
      esophagogastrofundoplication: report of a case].
AB  - The authors describe diagnosis and surgical treatment of a patient with
      iatrogenic diaphragmatic hernia following esophagogastrofundoduplication by
      Nissen's operation. The patient had presented a hiatal hernia with esophagitis
      chronic regurgitation and was submitted to esophagogastrofundoduplication. On the
      third postoperative day, the patient showed signs of dysphagia and intense
      dyspnea. The computerized tomography showed the presence of the gastric fundus
      and it's contents inside the leftpleural cavity. The patient was submitted to a
      left posterolateral thoractomy and an ischemic peptic ulcer in the gastric
      fundus, blocked by lung parenchyma was sutured. Then, the stomach was reduced
      into the abdominal cavity with diaphragmatic suture associated with esophageal
      and gastric fundus fixation to the right diaphragmatic pilar. The patient
      presented satisfactory immediate and late postoperative follow-up (1 year). The
      authors discuss and document aspects of diagnosis as well as surgical indication.

PMID- 9239901
TI  - [Lyme disease in Mato Grosso do Sul State, Brazil: report of three clinical
      cases, including the first of Lyme meningitis in Brazil].
AB  - The authors report the occurrence of the first three clinical cases of Lyme
      disease in Mato Grosso do Sul State, including the first case of Lyme meningitis
      in Brazil. These were identified by clinical and laboratorial criteria. Anti
      Borrelia burgdorferi antibody search was carried out through ELISA and Western
      Blotting techniques, the former providing identification of IgG class antibodies
      alone, in one only of those cases. Through Immunoblotting, the following features
      were found in serum: 5 IgG and 2 IgM bands for the first case; 7 IgG and 2 IgM
      bands for the second; and 5 IgG and 6 IgM bands for the third. In the latter,
      presence fo specific antibodies was searched in liquor, due to lymphomonocitary
      meningitis occurrence, and one IgM band was detected. After antibiotic therapy,
      all patients exhibited significant clinical and laboratorial improvement in their
      conditions along with symptom regression to the present moment.

PMID- 9239902
TI  - [Early adenocarcinoma of the duodenum--report of a case].
AB  - The early duodenal carcinoma is a very rare type of neoplasia, usually
      asymptomatic, its surgical treatment remains a controverse issue. In the present
      case an early duodenal carcinoma was incidentally found at the pathological
      specimen after a gastrectomy with BII reconstruction for a gastric adenoma
      unressectable by endoscopy. The patient is now alive for two years, without
      evidence of recurrence on follow-up.

PMID- 9239903
TI  - [Curriculum renewal and quality of the educational process].
AB  - Curriculum renewal may be one good way for the betterment of medical education in
      the perspective of educational development. The article identifies three
      otmization lines for curriculum renewal, in the sense of criteria of relevance,
      efficacy, and efficiency. They are: 1) anchoring the renewal in the vision of a
      three-dimension concept of competence; 2) emphasis on quality of learning; and 3)
      a quest for restructuring the learning settings. Implication and examples of, and
      some barriers against such moves are noticed. The author points out that
      curriculum renewal may be effective only when it is fostering the quality of
      learning.

PMID- 9239904
TI  - [Insulin-dependent diabetes mellitus in Santiago, Chile: the role of
      immunogenetic and environmental factors].
AB  - The role of HLA class II alleles in the genetic susceptibility to develop insulin
      dependent diabetes mellitus (IDDM) was examined by means of PCR and oligospecific
      probes in 63 IDDM children and 74 controls subjects. In diabetic patients we
      found a significant increase in the alleles frequency DR3, DR4, DQB1*0302 and
      DQA1*0301 compared to the control group, where the most prevalent alleles were
      DR2, DR14 (DRB1*1402), DQA1*0101 and DQA1*0201. All the risk genotypes in the
      diabetic group were similar than in other caucasian groups: DR3/DR4
      DQB1*0201/0302-DQA1*0301/0501 and DR4/DR4-DQB1*0302/0302-DQA1*0301/0301. The
      homozygote character no asp57 conferred an absolute risk (AR) of 3.87 and the
      marker Arg52 an AR of 5.78/100.000 bab year. The homozygosis for both markers (no
      Asp57 + Arg52) had an AR of 7.56/100.000 bab year. Regarding environmental
      factors associated with IDDM, our population under study showed a low prevalence
      of infectious agents (mainly mumps and rubella, specifically associated with
      IDDM) and a high prevalence of effective breast-feeding (over 3 months). These
      factors could be exercising a protector role in the development of IDDM. The
      factors that appear to be important in the low incidence of IDDM in Santiago de
      Chile are: the low prevalence of infectious agents related to IDDM, the high
      percentage of breast-feeding children in the population, the reduced frequency of
      susceptible molecules as DR3, DQB1*0201 (compared to other caucasian groups) and
      the presence of protective genotypes related to DR13 and DR14 observed in the non
      diabetic children.

PMID- 9239905
TI  - [Head-up tilt test in healthy asymptomatic patients].
AB  - The head-up tilt test has demonstrated to be useful in the study of patients with
      syncope of unknown origin for the diagnosis of neurocardiogenic syncope. Several
      publications have described different methods, with different results in cases as
      well as in controls. We performed a prospective study in a group of normal
      subjects in order to evaluate the methodology used in our population and to
      establish its specificity. A positive test was defined as the presence of syncope
      or presyncope and hypotension. The examination was carried out on a tilt table,
      five minutes at 0 degree, then at 70 degrees during 20 min. In the absence of
      syncope or presyncope an i.v. infusion of isoproterenol was started afterwards in
      order to increase the heart rate 30-50% over the baseline values and administered
      during 20 min at 70 degrees. Twenty one volunteers (14 male and 7 women; mean age
      26.7 +/- 3.5 years; range: 21-33 years) and body mass index 23.4 +/- 2.2 kg/m2
      were examined. Mean dose of isoproterenol was 3.1 +/- 0.9 micrograms/min (3.4 +/-
      1.1 in men and 2.6 +/- 0.7 micrograms/min in women, NS). During the phase without
      isoproterenol no subject developed hemodynamic alterations neither symptoms. One
      volunteer (4.8%) developed presyncope and systemic hypotension (52/28 mm Hg)
      accompanied with nodal rhythm after 14 min of isoproterenol at 70 degrees, and
      his examination was discontinued, with immediate recovery. Three other subjects
      developed asymptomatic transient nodal rhythm during the phase with isoproterenol
      and recovered spontaneously. No other complications were observed. It is
      concluded that head-up tilt test with isoproterenol at 70 degrees, with the used
      doses and heart rate increments, is highly specific (95%) to establish the
      diagnosis of a neurocardiogenic syncope.

PMID- 9239906
TI  - [Usefulness of immunocytochemistry in the identification of Mallory bodies.
      Theoretical analysis about their formation].
AB  - BACKGROUND: Mallory bodies are hepatocyte intracytoplasmic inclusions frequently
      observed in liver diseases. They contain altered intermediary filaments that have
      immunoreactivity with epidermic antikeratin antibodies (A-QEp). They also contain
      ubiquitin (Ubq) a 76 residue polypeptide that has an important role in the
      proteolysis of rapid exchange and abnormal cytosol proteins. AIM: To standardize
      an immunohistochemical method for the detection of Mallory bodies in percutaneous
      liver biopsies. METHODS: A-QEP and A-Ubq polyclonal antibodies were used in the
      study of 131 percutaneous liver biopsies obtained from patients with different
      liver diseases. Mallory body immunoreactivity was confirmed with immunoelectron
      microscopy. RESULTS: Mallory bodies had scanty immunostaining with A-QEp,
      specially in formalin fixed biopsies. There was a specific and sensitive staining
      with A-Uhq, that was not influenced by the fixation method. Immunoelectron
      microscopy demonstrated that Mallory bodies are partially formed by altered
      intermediate filaments. CONCLUSIONS: Antibodies against ubiquitin may be very
      useful for the detection of Mallory bodies in liver biopsies.

PMID- 9239908
TI  - [Prevalence of goiter in school-age children in the Pirque Zone. Effects of salt
      iodination].
AB  - BACKGROUND: Twenty years ago, Pirque was a zone with a goiter prevalence of 39%.
      AIM: To assess the effects of salt iodination on the prevalence of goiter in
      school-age children of this zone. SUBJECTS AND METHODS: School age children from
      four public schools in Pirque were examined, following WHO criteria for the
      diagnosis of goiter. Urinary iodine excretion was also measured. RESULTS: Five
      hundred ninety one males and 298 females aged 12.1 +/- 2.5 years were examined.
      Fifty seven children (9.6%) bad goiter. In 53 the goiter was grade I and in 4,
      grade II. No sex differences were observed. Minimal and median urinary iodine
      excretion values were 12.6 and 57.6 micrograms/dl respectively. CONCLUSIONS:
      Goiter prevalence dropped from 39 to 10%. The fact that iodine intake is over
      minimal recommendations, underscores the effectiveness of salt iodination.

PMID- 9239907
TI  - [Semiquantitative histopathologic analysis of chronic gastritis: extension and
      grading score].
AB  - Three endoscopic systematic biopsies were obtained from 261 patients showing
      chronic gastritis. Histopathologic features of chronic gastritis were graded from
      0 to 3 points according to the Sydney System. In addition, an extension and
      grading histopathologic score was applied. This score was obtained from the sum
      of qualified grades for each feature in all three samples. Inflammation,
      activity, atrophy, and intestinal metaplasia were predominantly grade 1 and H
      pylori density was predominantly grade 2. Only 2.6% of the sections without
      atrophy showed intestinal metaplasia, while 79.3% of the sections depicting grade
      2-3 intestinal metaplasia showed moderate to severe atrophy. Inflammation was
      more severe in the antral lesser curvature and the more severe atrophy was
      present in the antrum than in the corpus mucosa. Sydney System and extension and
      grading histopathologic score showed more extensive activity in patients older
      than 45 years. A lower histopathologic score of H pylori was seen in these
      patients. The presence of H pylori was directly correlated with inflammation
      severity and inversely with atrophy. These results, in accordance with data shown
      in the literature, suggest that the Sydney System and the extension and grading
      histopathologic score can be applied to compare chronic gastritis features in
      different groups of patients.

PMID- 9239909
TI  - [Bacterial urovirulence factors and their association with functional and
      anatomical abnormalities and recurrence of urinary tract infections in children].
AB  - BACKGROUND: Urinary tract infections in children are associated with functional
      and anatomical abnormalities of the urinary tract, they tend to recur and can
      cause permanent kidney damage. AIM: To study in children with urinary tract
      infections, microbiological factors associated to recurrence, functional and
      anatomical abnormalities of the urinary tract. PATIENTS AND METHODS: A
      prospective sample of children was incorporated into a follow-up protocol after
      their first episode of bacteriologically-demonstrated urinary tract infection. In
      all patients an abdominal ultrasound examination and a mictional
      urethrocystography were done and the presence of fimbriae was studied in isolated
      strains of Escherichia coli. RESULTS: Two hundred fifteen cases bad an adequate
      adherence to the study protocol, 190 caused by E coli. Fimbriated E coli strains
      were isolated with greater frequency from children with pyelonephritis than from
      those with a low urinary tract infection (50 and 28% respectively). The absence
      of fimbriae in E coli strains was associated with a higher risk of recurrent
      infections (odds ratio = 3, confidence intervals = 2-9.2) and an abnormal
      urethrocystography (odds ratio = 3, confidence intervals = 1.1-10.2).
      CONCLUSIONS: These data are consistent with foreign reports and support the need
      to study adhesins in E coli strains isolated from children with urinary tract
      infections.

PMID- 9239910
TI  - [Long-term follow-up of non-operated patients with symptomatic and asymptomatic
      cholelithiasis].
AB  - BACKGROUND: In Chile, cholelithiasis is a serious public health problem and there
      are no studies about its natural history. AIM: To assess the long term evolution
      of patients with symptomatic and asymptomatic cholelithiasis. PATIENTS AND
      METHODS: Ninety two patients with cholelithiasis (57 female), aged 15 to 80 years
      old and that were not operated, were followed during a period of 9 to 14 years.
      RESULTS: Thirteen patients were initially asymptomatic. Of them, seven bad
      complications or symptoms during follow-up and two were operated. Among the 69
      symptomatic patients, 38 (55%) were not operated during follow-up, and seventeen
      (25%) did not have symptoms again. Ten patients died during follow-up, four due
      to complications of biliary tract stones. CONCLUSIONS: The present finding
      suggest that the evolution of cholelithiasis in Chile is more aggressive than
      abroad, and an early surgical treatment is warranted.

PMID- 9239911
TI  - [Radiofrequency catheter ablation in patients with common atrial flutter].
AB  - BACKGROUND: Type 1 atrial flutter is produced by a reentry circuit located in the
      right atrium that can be interrupted applying radiofrequency in the inferior cava
      tricuspid valve isthmus. AIM: To report our experience in the treatment of atrial
      flutter with radiofrequency ablation. PATIENTS AND METHODS: Nine patients (eight
      male) whose ages ranged from 6 to 72 years old were studied. Two patients had an
      operated congenital cardiopathy, two had high blood pressure, one was subjected
      previously to radiofrequency ablation due to a left paraspecific pathway, one
      developed a cardiac failure secondary to tachycardia and three did not have
      evidences of cardiopathy. RESULTS: In two patients, atrial flutter was not
      interrupted. In the other seven patients, radiofrequency ablation was successful.
      There were three relapses in the first month after the procedure, of these, two
      patients were successfully treated again. After a mean follow up of 4.5 months,
      these patients are asymptomatic and without antiarrhythmic drugs. Analysis of
      obtained signals, showed that radiofrequency that interrupted atrial flutter
      always occurred in zones of double potentials. CONCLUSIONS: Radiofrequency
      ablation is an effective treatment for atrial flutter and the zone of successful
      ablation is associated to the presence of double atrial potentials.

PMID- 9239912
TI  - [Methods to estimate body composition in the elderly: a critical analysis].
AB  - The objective of this study was to compare the values obtained for total body fat
      obtained with deuterium dilution, anthropometry and bioimpedance in 41
      institutionalized elderly individuals (65-90 years old). The values obtained with
      each technique were compared using the graphic analysis proposed by Bland and
      Altman, that plots the difference between measurements with both methods against
      their average. In men (n = 20) and women (n = 21), the best degree of agreement
      was obtained between the values measured by deuterium dilution and those
      calculated from skinfolds (mean difference = 1.4% and 6.9%, respectively). The
      limits of agreement (+/-2SD), for skinfolds reached a maximum of 14.8% in men,
      and 16.8% in women. These values tend to underestimate fat in the obese and
      overestimate it in thinner subjects. For bioimpedance and deuterium dilution, the
      inter-method difference is significantly greater: 9.3% in men and 14.7% in women.
      This lack of agreement is attributed to the fact that the bioimpedance equipment
      utilizes equations validated for younger adults. In conclusion, estimation of
      body composition using skinfoids has the smallest difference compared to
      deuterium dilution, even though individual measurements are not clinically
      acceptable. Caution is recommended when using measurements of body composition in
      the elderly, due to large errors in the determinations.

PMID- 9239913
TI  - [Effects of estrogen supplementation on psychological variables in climacteric
      women].
AB  - BACKGROUND: The beneficial effects of estrogen supplementation in climacteric
      women are clear. However, their psychological effects are not well documented.
      AIM: To study the effects of estrogen supplementation on psychological variables
      in climacteric women. SUBJECTS AND METHODS: Forty postmenopausal women were
      divided in two groups to receive a daily dose of 2 mg oestradiol valerate and 2.5
      mg medroxyprogesterone acetate or an identical placebo during six months.
      Initially and at the end of the treatment period, they were subjected to a
      psychiatric interview and the Graffar, Hamilton and Eysenk personality tests were
      applied. Also, an Analysis of Verbal Behavior was used, that results in hope and
      hopeless scores. RESULTS: There were no differences in the initial assessment
      between the two treatment groups. In women receiving hormonal supplementation,
      the Hamilton score decreased from 11.2 to 4.9 (p < 0.002) and in women receiving
      placebo from 8.1 to 5.3 (NS). No other significant changes in psychological tests
      were observed. CONCLUSIONS: Hormonal supplementation decreases the Hamilton
      depression score in postmenopausal women.

PMID- 9239914
TI  - [Use of molecular biology techniques in clinical research, in Chile].
AB  - Medical investigation in Chile is beginning to apply molecular biology methods as
      diagnostic tools and in studies establishing the prevalence of pathologies with
      Mendelian or multifactorial genetic origin. In this way, we are getting nearer to
      the strategies used worldwide for these purposes. Two studies published in this
      journal, one about hemophilia A where an analysis of intron-18 and intron-7 of
      the Factor VIII gene was applied as strategy for the diagnosis of carrier state
      in a Chilean population, and the other one about insulin-dependent diabetes
      mellitus in Santiago, Chile, with an analysis from immunogenetics to some
      environmental risk factors, constitute good examples about this integration.

PMID- 9239915
TI  - [Severe cardiac failure as complication of primary hypothyroidism].
AB  - We report a 29 years old female admitted due to a congestive cardiac failure that
      failed to respond to therapy with furosemide and enalapril. Serum thyroid hormone
      profile showed a TSH over 40 microIU/ml, a thyroxine of 0.8 microgram/dl and a
      triiodothyronine below 20 ng/dl. Levothyroxine therapy was started with remission
      of cardiac failure. The study of thyroid function in patients with cardiac
      failure of unknown origin and resistant to therapy, should be bone in mind.

PMID- 9239916
TI  - [Diffuse fatty infiltration of the thyroid gland associated to amyloidosis in a
      patient with chronic renal failure].
AB  - We report a 26 years old male with secondary amyloidosis and chronic renal
      failure who consulted due to a rapidly growing goiter associated with coarseness
      and dysphagia. Serum levels of thyroid hormones and TSH were normal and a neck CT
      scan showed a big mass in the anterior and lateral regions, that compressed
      neighboring structures. The patient was subjected to a total thyroidectomy and
      the pathological study revealed a diffuse fatty and amyloid infiltration of the
      thyroid gland. There was no evidence of malignancy.

PMID- 9239917
TI  - [Oral vasodilators in the treatment of congestive heart failure].
AB  - Oral vasodilators have proved to be valuable drugs in the management of systolic
      or diastolic congestive heart failure. They produce a clinical and hemodynamic
      relief of preload, afterload or both during the resting state or exercise.
      Although left ventricular hypertrophy is an adaptative response to myocardial
      stress, in the long run it becomes an independent risk factor leading to
      diastolic dysfunction. At present, pharmacological regression of ventricular
      hypertrophy has a prognostic importance. Of the large number of available
      vasodilators, angiotensin converting enzyme inhibitors have proved to be the most
      successful drugs. They behave as afterload relievers, counteracting both the
      renin-angiotensin and adrenergic systems, but also are powerful inhibitors of
      cardiomyocite enlargement and interstitial connective tissue proliferation. This
      last structural change may revert the compromised diastolic function of the
      heart.

PMID- 9239918
TI  - [Surface law and allometric analysis of functions].
AB  - Since Rubner established in 1883 the "surface law", the basal metabolic rate
      (kcal/24 h) is expressed per square meter of body surface. This so-called
      biological law has been extrapolated to the standardization of several other
      functions as, for instance, to variables of the cardiovascular, respiratory and
      renal systems, which may lead to erroneous conclusions. The present paper is an
      attempt to establish, by means of the dimensional analysis and one of the
      theories of biological similarity, an allometric indexation procedure, which
      yields mass-independent numbers (MIN) for all functions which can be defined by
      means of the MLT-system of physics (M = mass; L = length; and T = time).

PMID- 9239919
TI  - [High lipase level in a patient with porphyria crisis: cause of confusion with
      acute pancreatitis].

PMID- 9239920
TI  - [Reproductive history of Chilean puerperal women hospitalized in a public
      hospital of the metropolitan region].
AB  - BACKGROUND: Maternal and infantile morbidity is closely related to the features
      of women's reproductive history. AIM: To study the reproductive behavior of women
      hospitalized due to labor or abortion in a public maternity of Metropolitan
      Santiago. SUBJECTS AND METHODS: One thousand women were interviewed about their
      reproductive behavior, 24 to 72 hours after pregnancy resolution. RESULTS: Ages
      of interviewed women ranged from 13 to 47 years old. Eighty seven percent had
      three children or less. The proportion of single women with a first pregnancy was
      62% and decreased to 9.3% in those with a second pregnancy. At the first
      pregnancy, 1.3% of women were using contraceptives, notwithstanding that 27% did
      not want to become pregnant. Most women had a birth spacing of 24 to 59 months.
      There was a low number of stillbirths in this sample. CONCLUSIONS: This work
      shows that studied women have pregnancies at low risk ages and an adequate
      parity.

PMID- 9239921
TI  - [1896-1996: a century of cardiac surgery. Ludwig Rehn and the first heart
      surgery].
AB  - In 1896 Stephen Paget published his book "Surgery of the Chest", where he
      affirmed that heart surgery had probably reached the limits of nature for any
      kind of surgery. This statement followed Billroth's who, few years earlier,
      sustained that the surgeon who attempted a suture of a wound in the heart was
      sure to loose forever the consideration of his colleagues. However, that very
      year of 1896 in Frankfurt, Ludwig Rehn succeeded in suturing a stab wound of a
      man's heart. By accomplishing this, he not only proved his colleagues wrong, but
      he made the heart, center of life and site of the soul, accessible to the
      surgeon, opening the way to what is today cardiovascular surgery.

PMID- 9239922
TI  - Hypertension in pregnancy and statistical power.

PMID- 9239923
TI  - Obstetric and perinatal aspects in patients with congenital heart diseases.
AB  - The benefits of surgical treatment for patients with congenital heart disease in
      relation to pregnancy are still controversial. We studied 48 pregnant women (mean
      age = 25 years) with surgically-corrected congenital heart diseases (Group 1).
      This included 15 cyanotic diseases: Fallot's tetralogy (11 cases); Ebstein's
      anomaly (2 cases); transposition of the great arteries (1 case); and double
      outlet of the right ventricle (1 case). We compared them to 52 pregnant women
      (mean age = 26 years) with untreated congenital heart diseases, which included 11
      cases of Eisenmenger's syndrome (Group 2). Group 2 showed a higher incidence of
      maternal death (12 vs. 0 percent; p = 0.01), perinatal mortality (15 vs. 0
      percent; p = 0.01) and prematurity (32 vs. 7 percent; p = 0.01). Spontaneous
      abortion (4 vs. 10 percent), Caesarean deliveries (48 vs. 66 percent) or growth
      retardation (13 vs. 28 percent) did not present any significant differences
      between these groups. Surgical treatment in patients with heart diseases is
      associated with a better maternal and fetal prognosis. Therefore, surgery must be
      considered when counseling patients with congenital heart diseases.

PMID- 9239924
TI  - Neurological examination in obsessive-compulsive disorder.
AB  - Recent studies suggest the occurrence of a neurological dysfunction in Obsessive
      Compulsive Disorder (OCD). The purpose of the present study was to verify the
      clinical value of a neurological evaluation in patients with the disease. We
      submitted 15 patients with OCD (five of whom were under clomipramine) and 15
      controls in a detailed neurological examination, including assessment of the
      neurological soft-signs. Eleven patients (73.3 percent) and four controls (26.7
      percent) presented abnormalities on examination. The main findings among the
      patients were: palmomental reflex (six cases); mirror movements (five cases);
      agraphestesia and dysdiadochokinesia (three cases). Three out of the four
      patients who had a normal examination were on clomipramine. Palmomental reflex
      was the main finding among the controls. These results, although preliminary,
      stress the interest and usefulness of performing a detailed neurological
      examination in OCD.

PMID- 9239925
TI  - Compliance with pharmacological treatment in outpatients from a Brazilian
      cardiology referral center.
AB  - To evaluate the degree of compliance with pharmacological therapy, and to
      identify predictors of non-compliance in outpatients from a cardiology referral
      center in Sao Paulo, Brazil, we studied 485 outpatients 230 (47.4 percent) males
      and 255 (52.6 percent) females, through an interview guided by a questionnaire
      during medical consultation. The ages ranged between 17 and 86 (mean 54, standard
      deviation 15) years. Heart disease and socioeconomic factors (residence, means of
      transport, educational level and professional status) were studied. In addition,
      we examined the drugs prescribed including: difficulties in taking them; the
      source of supply, and the patient's knowledge of the drugs. Assessment of
      compliance was based on the patients' response. The patients' answers were
      compared with the prescription and progress notes. Errors were recorded if the
      patient reported using one or more nonprescribed medicines. Compliance with
      therapy was recorded if the patient said the prescription was taken correctly
      without interruption and without error. The variables with significant
      differences in univariate analysis were further analyzed by multivariate log
      linear regression analysis. Noncompliance occurred in 286 (59 percent) of the
      patients, and was predicted by the reported difficulty in taking medication (P <
      0.001), and by the lack of knowledge of medication names (P < 0.001). Thus,
      noncompliance with medical therapy was common. The main predictors of non
      compliance were the reported difficulty in taking medication and inability to
      identify medicines' names.

PMID- 9239926
TI  - Comparison of red cell distribution width and a red cell discriminant function
      incorporating volume dispersion for distinguishing iron deficiency from beta
      thalassemia trait in patients with microcytosis.
AB  - The red cell distribution width (RDW), and another red cell discriminant function
      incorporating RDW (MCV2 x RDW/Hgb x 100) were determined in a group of 30
      patients with iron deficiency anemia, 30 patients with beta thalassemia trait,
      and 30 normal subjects. Both RDW and (MCV2 x RDW/Hgb x 100) mean values were
      significantly higher in iron deficiency anemia than in beta thalassemia trait (p
      < 0.001). Taking RDW equal or above 21.0 percent among microcytic anemia
      patients, we identified correctly 90.0 percent of patients with iron deficiency
      anemia. The sensitivity and specificity of the test were 90.0 percent (IC 95
      percent: 0.75-0.98) and 77.0 percent (IC 95 percent: 0.60-0.88), respectively.
      RDW values below 21.0 percent identified correctly 77.0 percent of beta
      thalassemia trait with a sensitivity and a specificity of 77.0 percent (IC 95
      percent: 0.60-0.88) and 90.0 percent (IC 95 percent: 0.75-0.96), respectively.
      Taking values of (MCV2 x RDW/Hgb x 100) above and below 80.0 percent as
      indicative of iron deficiency and beta thalassemia trait, respectively, we
      identified correctly 97.0 percent of those patients in each group. Both
      sensitivity and specificity were 97.0 percent (IC 95 percent: 0.84-0.99). These
      results indicated that the red cell discriminant function incorporating volume
      dispersion (MCV2 x RDW/Hgb x 100) is a highly sensitive and specific method in
      the initial screening of patients with microcytic anemia and is better than RDW
      in differentiating iron deficiency anemia from beta thalassemia trait.

PMID- 9239927
TI  - Placenta percreta with silent rupture of the uterus.
AB  - We report a case of placenta percreta diagnosed by ultrasound and color doppler
      image at the fourteenth week of gestation. Initial approach was a trial of IM
      methotrexate followed by total hysterectomy, during which was observed a rupture
      of the uterus with the adherence of the placenta to the posterior region of the
      bladder. We also present a literature review on the incidence of placenta
      percreta, etiology, diagnosis, treatment, and complications.

PMID- 9239928
TI  - Aspergillosis of the central nervous system.
AB  - The authors report an unusual case involving a 38 year-old man who developed a
      intracranial abscess caused by Aspergillus of the parietal lobe. Cerebral
      aspergilloma of an initial pulmonary origin developed in a patient with "Fungus
      Ball" secondary to tuberculosis sequelae. The diagnosis was made through the
      isolation of Aspergillus from the secretion of the brain abscesses. The patient
      was treated with drainage of the abscesses and Amphotericin B. He presented a
      progressive regression of the radiological images (brain and pulmonary) over a
      period of 55 days. This report emphasizes the importance of combined anti-fungal
      therapy and surgical resection as a treatment for cerebral aspergilloma.
      Furthermore, an early initiation of therapy should improve the prognosis in such
      cases.

PMID- 9239929
TI  - Systemic congenital lymphangiomatosis.
AB  - Systemic lymphangiomatosis is a rare disease characterized by the exageration of
      lymphatic channel proliferation, occurring in children and young adults. We
      describe an extremely rare case of congenital systemic lymphangiomatosis in a
      newborn who had ascitis and respiratory failure develop immediately after
      delivery. Death occurred during the first hour of life. Autopsy findings showed
      numerous cysts in soft tissues of the cervical area, mediastinum and diaphragm,
      and several other organs including the liver, spleen, thyroid and kidneys. The
      severe and diffuse involvement with cysts in both lungs by lymphangiomatosis was
      associated with poor prognosis and death in our case.

PMID- 9239930
TI  - Sexual disorders: demographic and diagnostic profile during one year of a
      multidisciplinary project.
AB  - Taking into consideration a study published 10 years ago on sexual disturbances
      of students at the University of Sao Paulo, the importance of the subject is
      discussed, along with the creation in 1993 of the Sexuality Project at the
      university hospital of the University of Sao Paulo School of Medicine. In its
      first year, this multidisciplinary project attended 140 patients with sexual
      dysfunctions (associated or not to other clinical manifestations); the majority
      were younger than 60 years-old, and 80 percent were male.

PMID- 9239931
TI  - Systematic reviews of medical literature and metanalyses.

PMID- 9239932
TI  - [Epidemiology of rinderpest and cattle plague in Mali: serological surveys].
AB  - Within the epidemiological surveillance of rinderpest in Mali a serological
      survey has been carried out on 58 herds of small ruminants. Out of 567 tested
      sera for the detection of antibodies against rinderpest 2 were positive. These
      sera were collected from two animals over 6 years old, probably infected during
      the last outbreak of rinderpest in Mali in 1986. Therefore, it can be assumed
      that the rinderpest virus has not circulated in Mali since that year. However,
      the infection rate among goats and sheep due to the PPR virus seemed to be high:
      74% of herds had already been infected. The prevalence of individual infection is
      32%. A similar serological survey was conducted on 450 cattleheads, without
      antibodies against the rinderpest virus and showed that 1.78% of these animals
      had been in contact with the PPR virus. With such a low infection rate in cattle,
      the PPR virus probably has no incidence in the epidemiology of rinderpest in
      Mali.

PMID- 9239933
TI  - [Experimental vaccination of broiler chickens against Newcastle disease in
      Burkina Faso using thermotolerant LaSota/A300 and V4/276 coated-millet vaccines].
AB  - Vaccination against Newcastle disease with the thermotolerant LaSota/A300 and
      V4/276 coated-millet vaccines was tried in Ouagadougou, Burkina Faso, by feeding
      298 European broiler chickens exhibiting maternal antibodies. Opportunistic
      infections, such as colibacteriosis, decimated 70-81% of the three vaccinated
      groups and 24% of control, before being eradicated by antibiotic therapy. The
      surviving chickens were challenged two months after vaccination with the Hertz
      33/56 virus strain. This resulted in 100% deaths in the control group, 78% in
      birds vaccinated with the V4/276, 7% in birds fed with LaSota/A300, and in no
      death in the group given both vaccines at one week interval. These last two
      groups also exhibited high titres of 1HA antibodies before the challenge. The
      lyophilized LaSota/A300 and V4/276 vaccines kept high viral titres after 8-34
      days' ambient temperature exposure during the cool season in Ouagadougou.

PMID- 9239934
TI  - Akabane virus: serological survey of antibodies in livestock in the Sudan.
AB  - An investigation was conducted to assess the prevalence of Akabane virus
      antibodies in domestic ruminants from different ecological zones of Sudan.
      Neutralizing antibodies were demonstrated in sheep, goats and cattle sampled
      between 1979 and 1980 from El Obeid, Nyala, Kassala, Jonglei and Sennar. The
      highest prevalence was in Jonglei where 27% of six sheep, 36% of eleven goats and
      47% of 90 cattle had antibodies to the virus. Although antibodies were
      demonstrated in 8% of 79 dams and 15% of 70 dams of two sentinel calf herds in
      Central Sudan at Shambat and Um Benein, respectively, none of their sentinel
      calves sampled between 1981 and 1983 had antibodies. Antibodies were subsequently
      detected in 8 (14%) out of 57 calves from Shambat and 5 (12%) out 40 from Um
      Benein of the random samples collected during 1985 from 1-3 year old calves. The
      implications of these results are discussed.

PMID- 9239935
TI  - [Causes of mortality of N'Dama breed cattle on the plateau of Sankaran, Faranah,
      Guinea 1993-1994].
AB  - The principal causes of mortality of 280 N'Dama breed cattle heads are presented
      with data obtained in the plateau of Sankaran, Faranah, Guinea in 1993-1994.
      Diarrhea caused 40.81% and 58.62% of calves mortality between birth and six
      months and between six and 18 months, respectively. Pasteurellosis provoked
      61.88% of cattle mortality up to 18 months of age. Hot and rainy seasons clearly
      increased the mortality rate of calves between birth and six months, whereas that
      of cattle increased notably up to 18 months of age during the rainy season. The
      absence of vaccination, sufficient care and new methods of husbandry were also
      responsible for cattle mortality.

PMID- 9239936
TI  - Rapid diagnosis of African horse sickness.
AB  - The rapid diagnosis of African horse sickness (AHS) during the incubation period
      using virus antigens in peripheral blood mononuclear cells (PBMC) and red blood
      cells (RBC) in a sandwich indirect enzyme-linked immunosorbent assay (ELISA) is
      reported. PMBC consistently gave higher positive ELISA results than RBC from
      blood collected during viraemia from clinically affected horses. The potential of
      the method described for wider application in rapid diagnosis and virus
      surveillance in susceptible equine populations, particularly in AHS-free and in
      enzootic areas, for effective control strategies is highlighted.

PMID- 9239937
TI  - Occurrence of cowpox-like lesions in cattle in Israel.
AB  - Two different clinical forms of cowpox infection, which occurred sporadically in
      one dairy herd and one beef herd, are described. The agent was identified by
      virologic test and by electron microscopy, when a characteristic orthopoxvirus
      was noted. No systemic illness was diagnosed with any of the two forms and
      recovery was observed in 3-4 weeks. The epizootiology of the infection is
      discussed.

PMID- 9239938
TI  - Prevalence of Salmonella, Listeria monocytogenes, Campylobacter spp., Yersinia
      enterocolitica and Cryptosporidium spp. in bulk milk, cows' faeces and effluents
      of dairy farms in Trinidad.
AB  - The prevalence of Listeria, Salmonella, Campylobacter, Yersinia and
      Cryptosporidium species in bulk milk, faeces of dairy cows and effluents of
      milking parlours from dairy farms in Trinidad was investigated. Of the 177 bulk
      milk samples studied, 3 (1.7%), 3 (1.7%) and 2 (1.1%) were positive for L.
      monocytogenes, Salmonella spp. and Y. enterocolitica, respectively, but were all
      negative for Campylobacter and Cryptosporidium species. From 333 faecal samples
      tested, L. monocytogenes, Campylobacter spp. and Cryptosporidium spp. were
      detected in 11 (3.3%), 19 (5.7%) and 7 (2.1%), respectively, which were
      significantly (P < 0.05; chi 2) higher than the detection rate (0%) for Yersinia
      spp. Salmonella spp. were isolated from 3 (0.9%) of the faecal samples. From 168
      effluent samples cultured, Campylobacter spp. were isolated from 7 (4.2%) samples
      while Salmonella was recovered from only 1(0.6%) sample with no sample positive
      for either Yersinia or Listeria. The difference was significant (P < 0.05; chi
      2). A total of 19 (73.1%) of 26 Campylobacter isolates exhibited resistance to
      one or more of the six antimicrobial agents tested. All 14 (100%) isolates of L.
      monocytogenes were resistant to at least one agent while all Salmonella and
      Yersinia enterocolitica strains were susceptible to all antimicrobial agents
      used. It was concluded that the five enteropathogens tested were present on dairy
      farms in Trinidad and the potential for milk-borne diseases, due to these
      pathogens, exists for consumers, emphasizing the need for good sanitary
      practices.

PMID- 9239939
TI  - Influence of Trypanosoma congolense infection on some blood inorganic and protein
      constituents in sheep.
AB  - The present study was designed to investigate the changes in plasma
      concentrations of zinc, copper, calcium, magnesium, inorganic phosphate, total
      protein, albumin, globulin, and serum iron and iron-binding capacity in sheep
      infected with Trypanosoma congolense. It was observed that infection did not have
      a significant effect on the plasma concentrations of zinc, copper, calcium,
      magnesium and inorganic phosphate. The serum iron concentrations in infected
      animals were higher, but not significantly so, than in control animals. Infected
      animals developed hypoalbuminaemia and hyperglobulinaemia while changes in total
      protein were not significant. The relevance of these changes to the pathogenesis
      of Trypanosoma congolense infection is discussed.

PMID- 9239940
TI  - [Evaluation of sensitivity of PCR for detecting DNA of Trypanosoma vivax with
      several methods of blood sample preparations].
AB  - Parasitological techniques show a low sensitivity for diagnosis of active
      infections with Trypanosoma sp. in livestock, particularly in the case of chronic
      infections. T. vivax antigen detection through antigen-ELISA developed by
      Nantulya and Lindqvist (1989) is not sensitive and specific enough for infection
      diagnosis. T. vivax DNA detection through polymerase chain reaction (PCR) using
      the oligonucleotides developed by MASIGA et coll. (1992) appears to be an
      alternative for a specific diagnosis of T. vivax active infections in livestock.
      Twenty-two blood samples containing known numbers of T. vivax/ml, ranging from 1
      to 1767, were prepared by dilution of T. vivax infected sheep blood into blood
      from a non infected sheep. PCR sensitivity was evaluated in several types of
      blood sample preparations: crude heparinized blood, plasma, lysed blood, buffy
      coat from haematocrit capillary tubes, pellet from plasma centrifugation, and DNA
      purified with an ion exchange resin commercial kit. Crude heparinized blood
      almost always inhibited PCR. Sensitivity of PCR with plasma and lysed blood was
      low, around 450 parasites/ml. PCR on buffy coat was more sensitive, but PCR
      products were sometimes little visible. Pellet of plasma centrifugation is an
      original, fast and economic preparation, whose PCR products are highly visible
      and which presents a high sensitivity: one hundred percent of the samples were
      positive when the parasitaemia was over 9 parasites/ml. DNA purification is
      slightly more time consuming and expensive, since it requires several
      manipulations and the use of a commercial kit, but it appears to be the most
      sensitive technique among those investigated: one hundred percent of the samples
      were positive when the parasitaemia was over 2 parasites/ml; however, PCR
      products were sometimes difficult to interpret. These last two techniques are
      recommended for a sensitive and species-specific diagnosis of active infections
      of livestock with T. vivax. These techniques should be evaluated for other
      pathogenic trypanosome species of livestock.

PMID- 9239941
TI  - Laboratory bioassays of deltamethrin, topically applied, during the hunger cycle
      of male Glossina tachinoides.
AB  - The susceptibility of mature and immature male Glossina tachinoides to topically
      applied deltamethrin was tested on successive days of their hunger cycle. Both in
      mature and immature flies, significant changes in tolerance were observed
      correlated to the digestion of the bloodmeal. In mature tsetse, the fly's fat
      level is also correlated to its susceptibility.

PMID- 9239942
TI  - The role of private-for-profit managed behavioral health in the public sector.
AB  - Managed behavioral health, once largely confined to private sector employees, has
      been growing rapidly in the public sector. Throughout the country, behavioral
      health services, particularly for Medicaid enrollees, are coming under the
      management of private-for-profit firms. The authors discuss these developments,
      and the controversies that have come about as a result. Several public/private
      models of managed behavioral health services are identified.

PMID- 9239943
TI  - "Unbundling" of state hospital services in the community: the Philadelphia State
      Hospital story.
AB  - This paper describes the organizational, financial, and programmatic changes
      surrounding the closure of Philadelphia State Hospital, and the conceptual model
      employed for "unbundling" or disaggregating the state hospital's services into
      community programs run by private non-profit agencies. The current status of the
      project is discussed as well as the long-term policy and research questions that
      remain to be answered.

PMID- 9239944
TI  - Problem type and referral to HMO mental health treatment.
AB  - The present study examined the cases of 353 patients seen in the outpatient
      department of psychiatry at a large west coast HMO. Comparisons were made between
      self-referred and physician-referred patients in the types of problems presented
      for treatment. Patients with relationship problems were self-referred more than
      those with adjustment, anxiety, and mood disorders who were more likely to be
      physician-referred. HMO patients with a self-referral option appear to enter
      mental health treatment because of relationship problems at a higher rate than
      their physician-referred counterparts.

PMID- 9239945
TI  - Racial differences in the utilization of public mental health services in
      Washington State.
AB  - This study analyzed racial differences in the use of public outpatient mental
      health services in four regions of Washington State. Patients in this study were
      enrolled in the state's mental health management information system, which
      contains detailed information about patient characteristics and service
      utilization. There were distinct racial differences with respect to baseline
      characteristics, and even after adjusting for these characteristics and region of
      the state as well, racial differences in the type and amount of services used
      persisted. In particular, African-Americans were more likely to use crisis
      services and were less likely to use individual or group treatment. This
      previously reported finding requires further exploration.

PMID- 9239946
TI  - Consumer empowerment in mental health organizations: concept, benefits, and
      impediments.
AB  - This article proposes a framework for promoting consumer empowerment in mental
      health organizations. Consumer empowerment involves consumer participation in
      organizational decision-making, program development and evaluation, access to
      resources, and opportunities for consumers to develop and run services as well as
      to maintain personal dignity and integrity. The benefits include increased
      service innovation, responsiveness to changes in the market place,
      accountability, as well as the enhancement of quality of care, the protection of
      consumer rights, among others.

PMID- 9239947
TI  - Assertive community treatment: organizational adaptation.

PMID- 9239948
TI  - A survey of hospital staff attitudes toward ethically problematic relationships
      with patients.

PMID- 9239949
TI  - Clinical practice guidelines: renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is the most common renal malignancy and is
      increasing at an annual rate of approximately 2% worldwide. Metastatic RCC is
      among the more chemotherapy-refractory malignancies, with a 5-year survival rate
      less than 2%. A variety of therapies are currently under investigation for the
      treatment of metastatic RCC, particularly involving immunotherapeutic agents such
      as interferon alfa. OBJECTIVES: To review and compare historical and current data
      that define practice guidelines in the treatment of RCC. DISCUSSION: Of the
      various treatment modalities available for RCC, only surgery with complete
      removal of tumor burden can be considered as potentially curative, since the
      tumor is resistant to chemotherapy, hormonal therapy, and radiation therapy.
      However, biologic response modifiers (BRMs)-particularly immunotherapeutic agents
      such as interferon alfa-have been extensively studied and appear to produce
      objective tumor regression in selected patients with advanced disease.
      CONCLUSIONS: In patients with metastatic RCC, performance status is the most
      important predictor of outcome, and should therefore be utilized for therapeutic
      decision making. Immunotherapy with BRMs such as recombinant interferon alfa and
      recombinant interleukin-2 has been associated with meaningful antitumor responses
      in selected patients. Combination therapy with recombinant interferon alfa,
      recombinant interleukin-2, and 5-fluorouracil may offer considerable promise, and
      the subcutaneous administration of recombinant interferon alfa and recombinant
      interleukin-2 may improve the tolerability and convenience of these cancer
      treatments by reducing side effects and permitting outpatient administration. As
      treatment expectations for metastatic RCC are limited, experimental approaches
      are warranted.

PMID- 9239950
TI  - Investigation of the PMN chemotaxis in periodontal disease.
AB  - The chemotactic responses of peripheral polymorphonuclear leukocytes in 36
      patients with rapidly progressive periodontitis (RPP) were compared to responses
      in 15 patients with localized juvenile periodontitis (LJP) and 10 patients with
      adult periodontitis (AP). In the RPP group, 13 (36%) patients exhibited reduced
      chemotactic activity and 7 (19%) exhibited activity. Compared to this, 12 (80%)
      of the LJP patients displayed reduced chemotactic activity. Among the AP-patients
      4 (40%) showed altered chemotactic activity including 1 (10%) with reduced
      chemotactic activity and 3 (30%) with increased activity. These results suggest
      that depressed chemotaxis is greatest in LJP, intermediate in RPP and least in
      AP.

PMID- 9239951
TI  - Plasma concentration of thyroid hormones in lambs fed poultry offal meal in
      replacement of soybean meal at two energy levels.
AB  - Sixty growing Najedi ram lambs (23.5 kg BW: 3 months old) were divided randomly
      to 6 equal groups. Each group was fed on different (isonitrogenous) diet, being
      either high energy (2.79 Mcal ME/kg DM) or low energy (2.15 Mcal Me/kg DM),
      supplemented with either 0.5 or 10% poultry offal meal (POM) in replacement of an
      equal amount of soybean meal (SBM). Feeding was ad libitum for 15 weeks
      experimental period. Thyroid hormones levels in plasma were determined during the
      last 7 weeks of the experiment and were related to feed intake and body weight
      during the same period. Lambs fed high-energy diets showed higher (P < 0.01)
      levels of both thyroxine (T4) and triiodothyronine (T3) compared to those fed low
      energy diets leading to lower T4 to T3 ratios. There was more conversion of T4 to
      T3 for more utilization of food by the lambs fed the 10% POM diet of the high
      energy content.

PMID- 9239952
TI  - Trypanosoma Mukasai (HOARE, 1932) in its biological vector Batracobdelloides
      tricarinata (BLANCHARD, 1897) and their life cycles.
AB  - Trypanosoma mukasai from the blood of the fish Clarias lazera underwent a
      multiplicative development in the gut of the fresh water leech B. tricarinata.
      The blood stream forms transformed into short flagellates and 2 days post
      infection, they divided by binary fission to produce numerous stumpy
      epimastigotes which later transformed into sphaeromastigotes, amastigotes,
      promastigotes and more numerous into long slender epimastigotes and metacyclic
      trypomastigotes. The epimastigotes and the metacyclic forms persisted in the
      leech for more than 21 days. The metacyclic forms developed into typical small
      slender trypomastigotes only in uninfected blood of Clarias lazera when the leech
      fed again. As time proceeded, the slender trypomastigotes developed into
      intermediate and finally into large broad form. The behaviour and the life
      history of the leech B tricarinata were studied in detail with special relevance
      to its activity and the development of eggs, embryos and immature leeches.

PMID- 9239953
TI  - White spot reduction when using glass ionomer cement for bonding in orthodontics:
      a longitudinal and comparative study.
AB  - The aim of this clinical study was to test the benefit from using glass ionomer
      cement (GIC) instead of a conventional diacrylate in bracket bonding for the
      prevention of white spot formation. Before treatment 7.2 per cent of all examined
      surfaces (n = 222) were classified as having white spots. No additional fluoride
      treatment other than fluoride toothpaste was prescribed. At debonding 8-39 months
      later, white spots were found in 24 per cent of the surfaces bonded with the
      cement, significantly lower than the 40.5 per cent bonded with the diacrylate (P
      < 0.01). At recall 12 months after debonding (examined surfaces n = 214) the
      frequency of surfaces with white spots was reduced to 22 and 24 per cent
      respectively. Re-examination after a further 12 months (n = 160) showed that
      white spot surfaces were less frequent with the cement (16 per cent compared with
      the diacrylate 29 per cent), but still significantly more frequent in both groups
      than before treatment. With longer treatment time (17 months) teeth bonded with
      diacrylate were more frequently affected with white spots (P < 0.05). Neither sex
      nor age affected the results. It is concluded that the use of a GIC for
      orthodontic bonding will result in a significant reduction in the number of white
      spot surfaces at debonding compared with the use of conventional diacrylate.
      Although markedly reduced in both groups, the number of affected surfaces was
      still higher 2 years after debonding than before treatment.

PMID- 9239954
TI  - Congenital temporomandibular joint ankylosis--a case report.
AB  - A case of congenital temporomandibular joint (TMJ) ankylosis which caused facial
      disfigurement, significant reduction in mouth opening, difficulties in feeding
      and breathing, and general interference with physical and mental development is
      presented. The wide range of manifestations exceed the typical picture of TMJ
      ankylosis and resemble a syndrome rather than an isolated defect of the TMJ.

PMID- 9239955
TI  - The aetiology of temporomandibular disorders: a philosophical overview.
AB  - Over the last 50 years many theories have been put forward to explain the
      syndrome currently called 'temporomandibular disorders'. However, it is doubtful
      whether any single theory fits all the complex features of this condition. The
      'multifactorial' explanation also appears flawed. On the assumption that a valid
      theory should fit the whole evidence, this paper starts by separating the
      'predisposing' from the 'initiating' factors, and notes that most existing
      theories appear to identify the former rather than the latter. The research
      material is examined in an effort to formulate a theory that is both logical and
      fits all the known clinical findings.

PMID- 9239956
TI  - Evaluation of the bond strength of different bracket-bonding systems to bovine
      enamel.
AB  - In an experimental study the bond strength of stainless steel, ceramic and
      plastic brackets to bovine enamel was investigated by tensile testing. The
      brackets were cemented to the enamel using a conventional two-paste orthodontic
      bonding resin, a light-cured, fluoride-releasing adhesive, a no-mix-orthodontic
      bonding resin and a light-curing glass ionomer cement. For evaluation of the
      experimental data the Weibull analysis was applied. The highest values for the
      Weibull modulus (m) and the 10 per cent probability of failure (sigma.10) were
      found in the tested plastic brackets (Dentaurum Edgewise plastic bracket and
      Spirit bracket) using a no-mix orthodontic bonding resin (System 1). However, the
      tensile stresses for the 90 per cent probability of failure (sigma.90) were over
      10 MPa and carried the danger of enamel fracture. Bracket bonding with glass
      ionomer cement cannot be recommended because of the low bond strength values for
      the 10 per cent probability of failure (sigma.10). The most favourable bracket
      bonding system concerning the Weibull modulus (m), the 10 and 90 per cent
      probabilities of failure (sigma.10 and sigma.90) and aesthetics was the ceramic
      bracket with the silane-treated base (Allure III) using the light-cured, fluoride
      releasing orthodontic bonding resin (Sequence). Bond fracture occurred
      predominantly between bracket and orthodontic bonding resin, with two exceptions.
      Concerning the ceramic bracket with the silane-treated base (Allure III) using
      the light-cured glass ionomer cement (Photac Fil), there was no preferential site
      of failure. Regarding the ceramic bracket with the silane-treated base (Allure
      III) using the light-cured, fluoride-releasing orthodontic bonding resin
      (Sequence), bracket fracture was seen more often than bond separation between
      bracket and enamel. When the bond failure was located at the enamel-orthodontic
      bonding resin interface enamel prisms could be identified on the adhesive site by
      scanning electron microscopy.

PMID- 9239957
TI  - Lay attitudes to dental appearance and need for orthodontic treatment.
AB  - In provision of advice about aesthetic treatment need, visual stimuli as a tool
      in communication may have some advantages compared with verbal descriptions, in
      particular when children are addressed. The Aesthetic Component (AC) of the Index
      of Orthodontic Treatment Need is an illustrated scale for rating of dental
      attractiveness developed in the UK and based on lay adults' ratings of dental
      photographs. This scale has also been recommended for use in patient education.
      The purpose of the present study was to establish a sociocultural standard of
      reference for Norway related to the AC, in order to examine the applicability of
      the scale as a tool in patient information. Samples of 137 children, 126 of their
      parents and 98 young adults were shown the 10 photographs comprising the AC. The
      subjects were asked to assess the photographs for dental attractiveness and
      orthodontic treatment need on a four-category rating scale. The findings
      indicated that, in general, photographs with an increasing scale point were rated
      as increasingly more unattractive. The majority (80-100 per cent) of the parents
      and young adults rated the five photographs on the unattractive end of the scale
      to be in need of treatment. The children were significantly less critical in
      their aesthetic judgements. Photographs representing borderline need, identified
      for these groups to be scale points 5 and 6, have a potential in guiding patients
      and parents in making informed decisions about aesthetic treatment need.

PMID- 9239958
TI  - Evaluation of treatment and post-treatment changes by the PAR Index.
AB  - To assess the outcome of orthodontic treatment, 224 cases treated in a
      postgraduate clinic were evaluated. Pre-treatment (T1), post-treatment (T2) and 5
      year follow-up (T3) study casts were assessed by the Peer Assessment Rating (PAR)
      Index. The influence of various factors upon treatment and long-term outcome was
      analysed. According to the PAR Index, orthodontic treatment reduced the
      malocclusions on average by 76.7 per cent, and at follow-up the reduction was
      63.8 per cent. Follow-up stability was good for 76.3 per cent of the cases. Some
      cases (4.0 per cent) even improved, while moderate to severe post-treatment
      relapse occurred in 19.7 per cent of the cases. Orthodontic treatment changed
      Angle Class I, II and III malocclusions to near ideal occlusion (PAR scores 4.4
      6.8). No long-term interaction between the groups was discovered. Sex and
      extraction/non-extraction treatments did not significantly affect the results.
      The initial PAR score accounted for 77.8 per cent of the variation in treatment
      PAR score change (T1-T2), and for 61.8 per cent of the variation of long-term PAR
      score change (T1-T3). Age at treatment start accounted significantly for the
      variability of treatment changes (P < 0.001). The PAR score at the end of
      treatment had some explanatory importance (R2 = 0.099) for the long-term (T1-T3)
      result. However, PAR score changes in the follow-up period were difficult to
      predict.

PMID- 9239959
TI  - Maxillary development revisited: relevance to the orthopaedic treatment of Class
      III malocclusions.
AB  - Normal development of the maxilla results not only from movements of its
      constituent skeletal units and bony apposition-resorption superficially, but also
      from the specific development of the antero-lateral regions. In Class III cases,
      correction of the skeletal dysmorphosis requires not only that the maxilla is in
      a correct position (in relation to the mandible) and that the correct occlusion
      is achieved, but also that there is good development of the exo-peri-premaxilla.
      This requires normalization of muscular posture (labio-mental, lingual, velo
      pharyngeal) and of orofacial functions (nasal ventilation, swallowing,
      mastication). Postero-anterior traction using an orthopaedic mask can only
      accomplish part of the treatment of Class III. The action must always be
      complimented by other therapy aimed at correcting the underdevelopment of the
      antero-lateral regions. Facemask therapy is not only simple sagittal distraction,
      but is truly a method for treatment of Class III which is well understood and
      achieves excellent results. Taking into account the great diversity of anatomical
      forms of Class III malocclusion, it is not surprising that extra-oral postero
      anterior traction gives widely varying results. The quality, however, depends
      principally on the method used. Orthodontists must not hesitate to call for the
      assistance of a surgeon each time the functional treatment is insufficient,
      particularly in cleft patients where the results depend more on surgical
      procedures, both primary and secondary, than on dentofacial orthopaedics.

PMID- 9239960
TI  - Relationships between the orientation and moment arms of the human jaw muscles
      and normal craniofacial morphology.
AB  - It has been suggested that subjects with increased vertical craniofacial
      dimensions have relatively oblique orientated jaw muscles with a reduced
      possibility to restrain the vertical component of craniofacial growth. To test
      this hypothesis, relationships were investigated between the spatial orientation
      of the jaw muscles and the craniofacial morphology. Computer reconstructions of
      the external shape of the jaw muscles of 30 adult males with a normal skull were
      made with the use of serial magnetic resonance imaging (MRI) scans. The
      orientation of the jaw muscles was defined by a regression line through the
      centroids of the serial cross-sections. Sagittal and frontal projections of the
      moment arms of the muscles were measured with respect to the centre of the
      ipsilateral condyle. Craniofacial morphology was analysed three-dimensionally
      using lateral head films and coronal MRI scans. The cephalometric data were
      analysed statistically using regression and factor analyses. Six cephalometric
      factors with Eigen values higher than 1 were correlated with jaw muscle
      orientation and moment arm data, using a multiple regression analysis. The
      anterior face height factor was significantly correlated with the orientation of
      the jaw opening muscles in the sagittal plane but was not significantly
      correlated with the orientation of the mandibular elevators. The sagittal moment
      arms of the mandibular elevators showed significant correlations with the factors
      describing the gonial angle and the posterior face height. It was concluded that
      the variation of spatial orientation of the human jaw closing muscles is
      predominantly associated with the variation of mandibular morphology (expressed
      by the gonial angle) and the posterior face height. The orientation of the jaw
      opening muscles shows significant relationships with anterior vertical
      craniofacial dimensions. The hypothesis that persons with an increased anterior
      face height have relatively oblique orientated jaw elevators was rejected.

PMID- 9239962
TI  - Breast cancer imaging--the issues and challenges. Proceedings of an international
      meeting. Dublin, Ireland, February 5-6, 1997.

PMID- 9239961
TI  - Dental occlusion and arch size and shape in karyotype 46,XY females.
AB  - The dental arch dimensions and occlusion of five Finnish individuals with
      complete testicular feminization were compared with their first-degree relatives
      and population female and male controls. The women with complete testicular
      feminization tended to have larger maxillary arch dimensions in all three spatial
      planes than the female and male controls, and larger mandibular arch dimensions
      in the transversal plane than the female controls. The results also suggested
      that the height/width ratio in the maxillary arch and width/length ratio in the
      mandibular arch would be greater in these females than in population females.
      Both the molar and canine sagittal relationships were more mesial than in the
      female and male population controls. As the phenotype in these 46,XY females is
      due to insensitivity to, or lack of androgens, it is suggested that the presence
      of the Y chromosome in these females leads to arch dimensions falling between
      those of normal females and males. This follows the same general dimensional
      pattern observed in their adult stature.

PMID- 9239963
TI  - Carotid endarterectomy: the outcome is not adversely affected by surgical
      residents.

PMID- 9239964
TI  - The South Carolina Geriatric Rural Initiative Project: the paraprofessional
      geriatric technician in care coordination.

PMID- 9239965
TI  - Pharmacologic management of common health problems in women. A professional
      evolution.

PMID- 9239967
TI  - Pharmacologic management of common lower respiratory tract disorders in women.
AB  - In a primary care setting, nurse-midwives will collaboratively manage common
      lower respiratory conditions that require pharmacologic therapy. As such, they
      must maintain up-to-date knowledge about the indications, use, and potential side
      effects of these medications. This article reviews the drugs most commonly used
      for the out-patient treatment of pneumonia, asthma, tuberculosis, and bronchitis
      (both acute and chronic). Differences among common oral antibiotics recommended
      by the American Thoracic Society are described. Inhaled bronchodilator and anti
      inflammatory medications are covered, as well as systemic corticosteroids. The
      use of isoniazid preventive therapy for latent tuberculous infection is described
      in detail, with brief mention made of other drugs used for active tuberculosis.
      Adjunct treatments including immunotherapy, vaccines, oxygen supplementation, and
      nicotine replacement for smoking cessation also are discussed.

PMID- 9239966
TI  - Pharmacologic management of common gastrointestinal health problems in women.
AB  - A wide variety of drugs are available for the treatment of common
      gastrointestinal health problems in women, including minor or serious as well as
      acute or chronic conditions. The midwife needs to be current in the pharmacology
      of over-the-counter as well as prescriptive agents for both pregnant and
      nonpregnant women. The drug classifications reviewed in this article include
      antacids, H2 receptor antagonists, antimicrobials, proton pumps, antiemetics,
      emetics, cholinergics, laxatives, prokinetics, and antidiarrheals. In addition,
      the physiologic principles are reviewed to enhance the understanding of how these
      drugs work.

PMID- 9239968
TI  - Pharmacologic management of cardiovascular problems in women.
AB  - Cardiovascular disease is the leading cause of death among women in the United
      States. Nurse-midwives play a unique role in screening their clients, especially
      because they will be caring for an increasing number of aging women as the
      population grows older. Risk assessment, health history, physical examination,
      and nonpharmacologic management of cardiovascular problems in women are discussed
      in the March/April 1995 issue of the Journal of Nurse-Midwifery. This article
      presents an overview of the most common cardiac drugs that nurse-midwives may
      encounter in treating these women and provides guidelines for referring patients
      who require medical intervention. Common medications to treat hypertension,
      coronary artery disease, and hyperlipidemia are detailed; in addition, mechanisms
      of action, therapeutic indications, dosage, and adverse effects are listed in
      tables for easy reference.

PMID- 9239969
TI  - Pharmacologic considerations and management of common endocrine disorders in
      women.
AB  - This article reviews the physiology and pathophysiology of selected endocrine
      glands. The common presenting clinical signs and symptoms are reviewed, and the
      initial laboratory tests that may establish the diagnosis are recommended.
      Diagnosis and management of hypothyroidism, hyperthyroidism, hyperparathyroidism,
      hypoparathyroidism, pituitary disorders, diabetes mellitus (types I and II),
      hypoglycemia, and disorders of the adrenal cortex are discussed. The clinical
      management of the most commonly encountered endocrine disorders seen in the
      primary care setting is described, and pharmacologic considerations are
      underscored.

PMID- 9239970
TI  - Pharmacologic management of common musculoskeletal disorders in women.
AB  - The range of musculoskeletal disorders encountered in primary care settings is
      broad, extending from simple injuries to complex chronic diseases. Assessment,
      management, referral, and pharmacologic intervention for many of these conditions
      may fall to certified nurse-midwives who increasingly are assuming primary care
      responsibilities.

PMID- 9239971
TI  - Primary care management of common dermatologic disorders in women. Pharmacologic
      considerations.
AB  - This article describes the clinical management of dermatologic disorders most
      commonly encountered in the primary care setting. The common presenting clinical
      signs and symptoms are reviewed, and the initial laboratory tests that may
      establish the diagnosis are recommended. Pharmacologic and nonpharmacologic
      treatments are reviewed. Diagnosis and management of disorders of the sebaceous
      and apocrine glands, disorders of the hair and pigmentation, fungal, viral, and
      bacterial infections, dermatitis, and infestations are discussed. A review of the
      care of skin burns and wounds is included as well as the diagnosis and management
      of urticaria.

PMID- 9239972
TI  - Psychopharmacologic management of women with common mental health problems.
AB  - This article reviews the essential aspects of the psychopharmacologic management
      of women with mental health problems, with particular emphasis on the role of the
      nurse-midwife as a primary care provider. The article also addresses the
      neurobiology of psychopharmacology, pharmacokinetics, and the selection of
      pharmacologic treatments used for depression, bipolar disorders, anxiety
      disorders, eating disorders, and psychosis. Considerations for the timely and
      appropriate referral for psychiatric intervention for women with psychiatric or
      pharmacologic emergencies are discussed, and issues relating to pregnancy,
      lactation, and reproductive health are included. The importance of the nurse
      midwife's role in ensuring women's access to and compliance with
      psychopharmacologic therapy is emphasized.

PMID- 9239973
TI  - Pharmacologic management of sexually transmitted diseases.
AB  - Vaginal complaints account for a significant proportion of visits to health care
      providers and are an ongoing challenge to every clinician in terms of diagnosis
      and management. Midwives traditionally have viewed such complaints as a
      disruption of the vaginal ecosystem and have adopted a combination of
      pharmacologic and nonpharmacologic treatment modalities in the management of
      vulvovaginitis and sexually transmitted diseases. This article presents a review
      of the literature that focuses primarily on the pharmacologic management of some
      of the more common sexually transmitted diseases. The management of vulvovaginal
      candidiasis and bacterial vaginosis also is reviewed. Although neither condition
      is sexually transmitted, they always should be considered in the differential
      diagnosis of vaginal complaints.

PMID- 9239974
TI  - Tipping the balance between science and industry.

PMID- 9239975
TI  - Recovering the clinical management role.

PMID- 9239976
TI  - International facilitation of doctoral education in nursing.

PMID- 9239977
TI  - Technologies of accountabilities.

PMID- 9239978
TI  - Academic freedom amidst competing demands.
AB  - Academic freedom means freedom from control in the fulfillment of the faculty
      roles of teaching and scholarship, but conflicts and misunderstandings regarding
      this right and responsibility occur, particularly during a time of rapid change.
      This article discusses the potential conflicts inherent in the academic setting
      between faculty and administration and differentiates between the role of a
      faculty member and the academic administrator in three areas: service,
      scholarship, and support.

PMID- 9239979
TI  - The trouble with caring: a review of eight arguments against an ethic of care.
AB  - Caring represents a large social movement that includes, but is not limited to,
      nursing. Some nurse scholars and feminists believe that caring can be used as the
      basis of a caring ethic, but critics argue that caring is not enough. This
      article reviews eight of the major arguments against a caring ethic and explores
      responses and alternatives to the arguments.

PMID- 9239980
TI  - Strategies for the development of contemporary nursing policy.
AB  - Legislated health care reform was a primary issue of concern and activity during
      the early part of the Clinton administration. Nursing was among those disciplines
      with proposals for change. Although legislated health care reform failed to
      achieve congressional approval, the momentum for change continued and has
      contributed to a newly emerging, market-driven health care environment.
      Professional leadership is needed to lend perspective to the many health care
      innovations. Nurses should play an important role in this leadership, but they
      must rise above some of their own divisiveness to do so. Strategies for the
      development of nursing policy aimed at achieving this goal are discussed.

PMID- 9239982
TI  - Critical thinking skills and dispositions of baccalaureate nursing students--a
      conceptual model for evaluation.
AB  - To date, little has been written on specifically what critical thinking is and
      what the scores reported on critical thinking instruments actually represent.
      This lack of specificity provided the impetus to examine critical thinking skills
      and dispositions of baccalaureate nursing students, to ascertain whether or not a
      significant difference exists between academic levels, and to ascertain, using
      the California Critical Thinking Skills Test (CCTST) and the California Critical
      Thinking Disposition Inventory (CCTDI), whether a relationship exists between
      nursing students' critical thinking skills and their critical thinking
      dispositions. The conceptualization of critical thinking consisting of two
      dimensions, cognitive skills and affective dispositions, developed by a panel of
      experts comprised the conceptual framework for this study. A cross-sectional,
      descriptive, comparative, and correlational study was undertaken in which two
      instruments, CCTST, Form A, and the CCTDI were administered to a convenience
      sample of nursing students representing five academic levels. The sample in the
      statistical analyses comprised 328 students. Results indicated that the total
      critical thinking mean score for students at each level reflected percentile
      ranking ranging between 48 and 65 per cent. The mean score for the critical
      thinking subscale, inference, had the lowest percentile rankings, ranging between
      37 and 55 per cent. The analysis of variance (ANOVA) statistical analysis
      indicated that students at the junior I level had the highest critical thinking
      mean scores, and students at the sophomore II level attained the lowest scores,
      reflecting a significant difference (P < or = .05). ANOVA also indicated a
      significant difference in the total critical thinking disposition mean scores
      between students at the junior I and senior I and II levels and those at the
      sophomore II level (P < or = .0000). Results indicated weak truth-seeking
      disposition scores among students at all levels. Pearson Product Moment
      Correlation Coefficient yielded a significant positive relationship between
      critical thinking skills and critical thinking dispositions (P < or = .01). The
      conceptual model, as well as its relevancy to the professional standards of
      Essentials for College and University Education for Professional Nursing (AACN,
      1986), is presented. Recommendations are discussed in regard to nursing
      education, curriculum, and research.

PMID- 9239981
TI  - The lived experiences of students in nursing: voices of caring speak of the tact
      of teaching.
AB  - The purpose of this phenomenological, Heideggerian hermeneutical study was to
      describe the lived experiences of 23 undergraduate nursing students in relation
      to their perceptions of "caring" experiences in their nursing programs. Data were
      collected by the primary investigators at a statewide nursing convention, with
      students relating stories of critical student experiences related to caring.
      Themes related to caring experiences included "caring as offering," "leaps ahead
      caring," and "creating a caring place." A recurrent pattern of "power inherent in
      teaching" was identified across student narratives, suggesting the need to study
      how teachers can use the tact of teaching to empower students. Implications drawn
      from the data suggest the need to explore how nursing students' learning is
      shaped by caring interactions with nurse clinicians and other health
      professionals as well as with nursing faculty.

PMID- 9239983
TI  - Organizational effectiveness: toward an integrated model for schools of nursing.
AB  - Assessing the quality of academic institutions involves much more than the
      opinions of peers or experts. Examination of the organizational effectiveness of
      schools of nursing has been neglected. Current emphasis on assessing educational
      outcomes has diverted attention from the construct, organizational effectiveness,
      and more comprehensive theory-driven approaches to evaluation. This review of the
      organizational effectiveness literature focuses on the major assessment models:
      goal attainment, human relations, open systems, internal processes, culture, and
      life cycle. Attention is given to the influence of organizational maturation on
      an integrated model of organizational effectiveness. Selected macrolevel studies
      of schools of nursing are examined, and an agenda for nursing research is
      proposed.

PMID- 9239984
TI  - International collaboration for home care education, Part I: Creating the
      partnership.
AB  - This two-part series describes the collaborative summer home care nursing program
      for Korean nurses conducted by the Frances Payne Bolton School of Nursing, Case
      Western Reserve University, Cleveland, OH, in cooperation with the College of
      Nursing of Yonsei University, Seoul, Korea. Part I focuses on the development of
      the collaboration, and part II focuses on the content of the three-week summer
      home care program and describes related issues and problems as well as suggests
      solutions. The series concludes with the findings on the program from the
      postprogram evaluations of students, preceptors, and patients. The collaborative
      educational program was developed to give Korean home care nurses an opportunity
      to gain clinical experience in home care nursing in the United States so that
      they could learn how to deliver better-quality home care for patients and their
      informal caregivers. Therefore, the program focused on practice-oriented lectures
      and clinical experiences.

PMID- 9239985
TI  - Multiple authorship: issues and recommendations.
AB  - The increase in multidisciplinary research has led to a subsequent expansion of
      multiple authored articles in nursing as well as other disciplines. Although
      there are benefits to multiple authorship, there also are areas of possible
      conflict. The lack of adequate guidelines to address issues that may arise from
      multiple authorship heightens the possibility of disputes. Developing a blueprint
      for the preparation and presentation of papers emanating from a research team's
      work early in the project can avoid conflicts and ensure that the efforts of the
      appropriate individuals are reflected in the publications. This article discusses
      several issues related to authorship, including the assignment of authorship
      credit, the increased pressures to publish, and the complexity of authorship
      issues associated with multisite studies. The authors offer recommendations to
      reduce problems that may arise among members of a research team because of
      authorship issues. In addition, they include the guidelines that their
      multidisciplinary research team developed early in their project.

PMID- 9239987
TI  - Energy cost of treadmill walking.
AB  - BACKGROUND: The purpose of this study was to determine if energy cost of walking
      (VO2) could be accurately predicted with the simple models which analyze
      relationship oxygen uptake-speed of walking. A model to predict energy cost of
      treadmill walking was published firstly 29 years ago. METHODS: Employing the new
      modification of this model from 1986 to analyze VO2-speed of walking relationship
      leads to the elaboration of a simple linear model, two-compartment linear model,
      polynomial model of second order and monoexponential model of the metabolic cost
      of treadmill walking. To verify and compare these models 87 males, age ranged
      from 19 to 62 years, were evaluated on a motor driven treadmill. They walked at
      0% grade at various velocities ranged from 3 to 12 km.h-1. RESULTS: The linear
      model has in range of intensities 3-12 km.h-1 a form of VO2.kg-1 (ml.kg-1.min-1)
      = 5.228*v (km.h-1)-11.158, r = 0.812, S(EE) = 4.16 ml.kg-1.min-1. The two
      compartment linear model has in range of intensities of 3-7 km.h-1 a form of
      VO2.kg-1 = 3.207*v(km.h-1)-1.777, r = 0.932, and S(EE) = 1.5. In the range of 7.1
      12 km.VO2.kg-1 = 7.120*v-29.168, r = 0.901, S(EE) = 3.78. In the range of
      intensities from 3 to 12 km.h-1 a polynomial model was found in the form VO2.kg-1
      = 4.501-0.108*v + 0.379*v2, r = 0.891, S(EE) = 4.43, and the exponential model
      had a form VO2.kg-1 = 4.360*exp(0.223*v), r = 0.861, S(EE) = 6.84. All these
      correlation coefficients were highly significant (p < 0.001 in all cases).
      CONCLUSIONS: It was concluded that when applied to adult population, the models
      provide reasonable estimate of the actual requirement for treadmill walking
      provided the subjects in a oxygen uptake steady-state. As other researches for
      VO2/step we have found U-shaped curves of coefficient energy cost of walking. The
      minimum was at speed about 4 km.h-1. This finding support the speculation that
      does exists the "optimal" speed of moving which reflects the minimal energy
      expenditure during the walking.

PMID- 9239986
TI  - Work-exhaustion time relationships and the critical power concept. A critical
      review.
AB  - The present review is focused on the physiological meanings of the critical power
      concept proposed by Scherrer in 1954 and its applications to general exercises
      such as running, cycling and swimming. Since the first studies on the critical
      power of local exercises, many studies have found that critical power is
      correlated with indices which are related to aerobic endurance such as maximal
      oxygen uptake, ventilatory threshold, OBLA or maximal lactate steady state. In
      fact, the relationship between exhaustion time t(lim) and the Work Wlim (or
      Distance Dlim) performed at exhaustion is not exactly linear and, consequently,
      the power-t(lim) equation is not a true hyperbola. The effect of the range of
      t(lim), used in the calculation of the slope of the Wlim-t(lim) relationship
      (called critical power) are discussed. When critical power is calculated from
      short supramaximal exercises, this power is higher than the power output which
      corresponds to a lactate steady state (or an oxygen uptake steady state) and does
      not correspond to a power output which can be sustained a long time. The authors
      present experimental data collected during local (knee extension) and general
      (running and cycling) exercises which suggest that critical power could
      correspond to a steady state provided that critical power is calculated from
      heavy submaximal exercises only (t(lim) ranging between 6 and 30 min). It is
      difficult to predict exhaustion time from critical power or critical velocity
      because of the hyperbolic nature of the power-t(lim) relationship. On the other
      hand, a large error in the measure of t(lim) should have a small effect on the
      calculation of critical power or velocity. In contrast, the value of Y intercept
      of the Wlim-t(lim) (or Dlim-(t(lim)) relationship should be sensitive to errors
      in t(lim).

PMID- 9239988
TI  - Influence of an unaccustomed increase in training volume vs intensity on
      performance, hematological and blood-chemical parameters in distance runners.
AB  - The hypothesis was tested that high-volume endurance training can be monitored
      using hematological and blood-chemical parameters as markers of an early stage in
      the overtraining process. Eight experienced distance runners participated in a
      prospective, experimental, controlled study. The study consisted of an
      unaccustomed average 103% increase in training volume (ITV) within 4 weeks
      (average final volume: 174.6 km per week). A year later, 9 runners performed the
      additional 4-week control study that consisted of an unaccustomed average 152%
      increase in intensive training measures (ITI). Average total volume amounted to
      61.7 km (week 1) and 84.7 km (week 4). Seven athletes participated in both
      studies. Simultaneously to performance diagnostics, a comprehensive pattern of
      hematological and blood-chemical parameters was determined. During ITV,
      submaximum running performance was improved after 2 weeks, stopped improving
      between week 3 and 4; maximum performance did not increase rather was decreased
      after week 4 compared to baseline as indication of an early stage in the
      overtraining process. During ITI, submaximum and maximum running performances
      increased continuously. In contrast to ITI, the following parameters decreased
      significantly during ITV: White blood cell count, serum iron, ferritin, VLDL
      (very low density lipoproteins), LDL (low density lipoproteins)-cholesterol,
      albumin, resting and maximum free fatty acid, maximum lactate, resting,
      submaximum and maximum glucose, summed amino acid, resting, submaximum and
      maximum ammonia concentrations, whereas prothrombin time increased significantly.
      During high-volume endurance training a multifactorial and longitudinal approach
      considering either a performance incompetence and an individually different range
      of symptoms and alterations in hematological and blood-chemical parameters can
      help to recognize an early stage in the overtraining process.

PMID- 9239989
TI  - Lactic threshold vs ventilatory threshold during a ramp test on a cycle
      ergometer.
AB  - OBJECTIVE: The purpose of this investigation was to study the relationship
      between the lactate (LT) and the ventilatory threshold (VT) during a ramp
      protocol in cycle ergometry. PARTICIPANTS: Thirty nine trained male subjects were
      selected as subjects. EXPERIMENTAL DESIGN: All the subjects performed a maximal
      ergometric test on a cycle ergometer consisting of a ramp protocol (increases of
      25 W.min-1). The anaerobic threshold (AT) was determined using both ventilatory
      gas analysis (VT) and lactate measurement (LT). All the data related to the VT
      and LT were expressed in work rate (W), VO2 (ml.kg-1.min-1) and heart rate (bpm)
      and expressed as mean and standard deviation. Lactate threshold (LT) and
      ventilatory threshold (VT) were compared using the Student's "t"-test for paired
      data. Correlation coefficients between both variables were also calculated.
      Statistical significance was accepted at the 5% level. RESULTS: Results showed
      significant differences (p < 0.05) between mean values of VT and LT when both
      expressed either as heart rate (bpm), work rate (W), or VO2 (ml.kg-1.min-1).
      CONCLUSIONS: It was concluded that LT and VT occur at different exercise
      intensities during ramp protocol exercise on a cycle ergometer.

PMID- 9239990
TI  - Correlations between short-course triathlon performance and physiological
      variables determined in laboratory cycle and treadmill tests.
AB  - The aim of this study was to investigate the relationships between physiological
      variables measured in graded cycling (CM) and treadmill running (RM) maximal
      tests and the performance of a short-course triathlon (1 km swim, 30 km cycling
      and 8 km running) in recreational triathletes. Ten male athletes with mean (+/
      SD) age of 27.4(+/-5.7) years and maximal oxygen consumption (VO2peak) of 63.3(+/
      8.95) mL.kg-1.min-1 participated in the study. The results showed that the
      VO2peak and VO2 at ventilatory threshold (VO2VT) determined in CM were
      significantly correlated to the overall and running times of the triathlon (r = 
      0.64 - 0.77, p < or = 0.05). The VO2peak and VO2VT determined in RM were also
      correlated to the running time when expressed as mL.kg-1.min-1 (r = -0.73, p < or
      = 0.05). The VT expressed as %VO2peak in both tests showed no significant
      correlations to triathlon performance. It appears that it is the absolute aerobic
      capacity of these athletes being critical to maintain a high exercise intensity
      in the triathlon, especially during the running segment. The mean heart rate (HR)
      measured in four subjects during the cycling and running segments of the
      triathlon was similar to the HR at VT determined in CM, which indicated that
      these athletes could maintain an exercise intensity close to the VT level during
      the competition. There was no significant correlation found between the swimming
      time and physiological variables measured in the laboratory cycling and running
      tests, which could be explained by the specific skills and economy of movement
      required in these exercises.

PMID- 9239991
TI  - Accuracy of Calorie Counter method to assess daily energy expenditure and
      physical activities in athletes and nonathletes.
AB  - OBJECTIVE: The aim of this study was to examine the accuracy of the Calorie
      Counter personal activity computer (CC method) for athletic activity. DESIGN: An
      observational study for a week or on a day. SETTING: Healthy Japanese volunteers.
      PARTICIPANTS: Nonathletes (54 males and 53 females) and 38 male athletes, with
      ages between 13 and 73 years old. MEASURES: Daily energy expenditure and weekly
      physical activity were simultaneously assessed using the CC method and a daily
      record on physical activity (daily record method) for a week for the nonathletes
      and one day for the athletes. RESULTS: Mean daily energy expenditures were 9630
      (standard deviation, SD, 1250) kJ.d-1 by the CC method, compared with 9530 (SD,
      1120) kJ.d-1 by the daily record method for male nonathletes; 7822 (SD, 768) kJ.d
      1 and 7790 (SD, 810) kJ.d-1, respectively, for female nonathletes; and 1120 (SD,
      1520) kJ.d-1 and 11580 (SD, 1580) kJ.d-1, respectively, for athletes. The
      correlation coefficients between daily energy expenditures by these two methods
      ranged from 0.72 to 0.90. Mean daily physical activities were 1520 (SD, 637) kJ.d
      1 by the CC method, compared with 1580 (SD, 691) kJ.d-1 by the daily record
      method for male nonathletes; 1033 (SD, 318) kJ.d-1 and 1080 (SD, 346) kJ.d-1,
      respectively, for female nonathletes; and 2770 (SD, 914) kJ.d-1 and 3250 (SD,
      1090) kJ.d-1, respectively, for athletes. The correlation coefficients between
      daily physical activities by these two methods ranged from 0.56 to 0.96.
      CONCLUSIONS: Our results suggest that the CC method may be reliable enough for
      assessing the energy expenditure in athletes as well as in nonathletes during
      free-living activities.

PMID- 9239993
TI  - Aggression and violence in sport: an ISSP position stand.
AB  - Violent and aggressive behaviours have become common in a large variety of sport.
      The antecedents and consequences of such behaviours are outlined in the position
      statement issued by the International Society of Sport Psychology (ISSP). The
      ISSP recommends several actions be taken to minimize such acts in sport and
      encourages education of young athletes in line with fair-play ethics.

PMID- 9239992
TI  - Leucine supplementation and serum amino acids, testosterone, cortisol and growth
      hormone in male power athletes during training.
AB  - OBJECTIVE: The purpose of the present study was to examine the effects of leucine
      supplementation on the amino acid and hormone profile during training.
      EXPERIMENTAL DESIGN: The study was a randomised double-blind cross-over study
      during 10 weeks of training. SETTING: The study occurred during a sport training
      period. PARTICIPANTS: Twenty adult male track and field power athletes finished
      the study. INTERVENTIONS: The subjects were given leucine (50.0 +/- 3.3 mg/ kg
      body weight per day) or placebo tablets. MEASUREMENTS: The measurements were
      carried out before, in the middle of, and after 10 weeks. RESULTS: The serum
      leucine concentration decreased significantly (p < 0.05) in the placebo group, by
      20.1% (from 189 +/- 45 to 151 +/- 21 mumol/l) during the first 5 weeks, but not
      during the second 5 weeks (180 +/- 61 vs 154 +/- 23 mumol/l). When leucine was
      taken there were no changes in the serum leucine concentration. The total serum
      amino acid pool decreased significantly (p < 0.01) in all subjects, by 21.2%
      during the 10-week training period. The decrease occurred mostly during the first
      5 weeks. Glutamine decreased (37.1%; p < 0.01) most of the single amino acids.
      The serum testosterone concentration increased by 20.7% (p < 0.05) and the serum
      cortisol concentration by 8.0% (p < 0.05) in all subjects during the first 5
      weeks. During the second 5 weeks the testosterone concentration decreased by
      19.0% (p < 0.001). CONCLUSIONS: The present findings indicate that on a daily
      protein intake of 1.26 g/kg body weight the serum concentrations of amino acids
      are lowered considerably and earlier than the decrease in the serum testosterone
      concentration during the training season in adult male power athletes. The
      leucine supplementation of 50 mg/kg body weight per day appears to prevent the
      decrease in the serum leucine concentration during intensive training.

PMID- 9239994
TI  - A short communication regarding the article by M. Kara et al. "Determination of
      the heart rate deflection point by the Dmax method." (J Sports Med Phys Fitness
      1996;36(1):31-4)

PMID- 9239995
TI  - Some comments concerning the paper by McNaughton, Cooley, Kearney, Smith "A
      comparison of two different Shuttle Run tests for the estimation of VO2max". (J
      Sports Med Phys Fitness 1996;36:85-9).

PMID- 9239996
TI  - Aging is a women's issue.

PMID- 9239997
TI  - Demographic trends for the aging female population.
AB  - Female life expectancy is higher at birth and at age 65 than the corresponding
      male life expectancies in the United States--and in most developed countries. In
      contrast, age-specific prevalences of chronic disability and institutional
      residence are higher for elderly women than for elderly men. This apparent
      contradiction results from the different morbid conditions causing chronic
      disability in US women and men. However, morbidity differentials do not explain
      all the gender differences in either disability or mortality. To test for general
      age-related factors causing female survival advantages, we analyzed male and
      female mortality and disability data from national longitudinal surveys of the
      health and functional status of elderly men and women from 1982, 1984, and 1989.
      Gender-specific mortality functions and models of disability changes were used to
      construct male and female cohort life tables where mortality and disability
      interact over the life of the modeled population. Even in populations where
      observation started 15 years after menopause, there were significant gender
      differences in the rate of aging estimated conditionally on chronic disability.
      Possible causes of gender differences in late-age mortality and their
      implications for the future health of the US female population are discussed.

PMID- 9239998
TI  - An economic profile of American older women.
AB  - This literature review examines the economic status of American women age 65 and
      older in view of their longevity, employment patterns, sources of income, income
      levels, potential for poverty, and their economic stake in current public policy
      debates and actions regarding Social Security, Medicare, Medicaid, and SSI.
      Although women live longer and therefore must stretch their financial resources
      further than men, longevity is not the sole cause of their economic
      vulnerability. Rather, it is associated with historical patterns of economic
      dependence on men; with sporadic, often low-wage or nonexistent employment
      histories; and with public policies and programs that place undue financial
      pressures on older women. Living alone is a major risk factor for poverty, and
      women of color are doubly at risk, with the highest poverty rates of all the
      elderly. Middle-class women face the possibility of "cycling into poverty" after
      widowhood, especially if their husbands suffered long, costly illnesses or
      spousal pensions shrink or disappear. While women's improving educational and
      work opportunities are likely to result in improved financial circumstances for
      future generations of older women, it will be necessary to move beyond their
      personal efforts to the public policy arena for solutions to the often
      devastating effects of uninsured health care costs, pension inequities, and other
      pressing economic concerns for older women.

PMID- 9239999
TI  - The impact of disability in older women.
AB  - As the size of the older population grows and mortality rates continue to
      decline, an unprecedented number of women will live to very old age. Recent
      research has provided a better understanding of the impact of disability in the
      older population, risk factors for disability, and the consequences of
      disability. Older women have consistently been found to have higher prevalence
      rates of disability than men of the same age. This difference does not result
      from women developing disability more often than men, but rather surviving longer
      with their disabilities. This effect may be explained at least in part by the
      differences in the diseases underlying disability in older women and men.
      Interventions that can reduce the burden of disability in the aging population
      are now being explored. In the next century, it will be increasingly important to
      develop new prevention and treatment strategies that address the functional
      consequences of chronic disease in the population of women living to older and
      older ages.

PMID- 9240000
TI  - Osteoporosis and its management in older women.
AB  - Osteoporosis is not an inevitable accompaniment of aging. Rather, it evolves
      silently over a lifetime, with its attendant morbidities occurring late in life.
      It is no longer the standard of care to wait until the primary morbidity strikes
      to begin therapy. A better outcome is always achieved when the individuals at
      risk are identified early, lessening or even preventing morbidity such as
      osteoporotic fractures. Recent surveys show a reluctance on the part of many
      physicians to diagnose or treat osteoporosis in their patients. A second level of
      resistance is often seen even after fractures occur. Either scenario is
      particularly unfortunate as therapies currently exist that can significantly
      reduce future morbidity and probably mortality. Physicians must recognize that
      patients who have had one fracture are at significantly greater risk to sustain
      more fractures and are more likely to suffer chronic debilitating musculoskeletal
      failure. Therefore, in the elderly fracturing patient, even more intensive
      intervention (fracture prevention) is required.

PMID- 9240001
TI  - Chronic pain in the lives of older women.
AB  - Despite the prevalence of chronic pain among the elderly and older women in
      particular, the geriatric literature has given very little attention to it. Older
      women experience a range of undesirable functional, psychological, and social
      consequences as a result of living with chronic pain. This paper focuses on
      chronic pain in the lives of older adults. Age, gender, social history, and
      cultural expectations may influence individual responses to chronic pain, thus
      necessitating a multidimensional approach to its assessment and treatment.
      Strategies for effectively managing chronic pain experienced by the elderly
      include both pharmacologic and nonpharmacologic regimes. To illustrate the
      biopsychosocial nature of chronic pain, specific attention is given to
      osteoporosis, a prevalent disease among older women in which pain plays a major
      role.

PMID- 9240002
TI  - Why Alzheimer's disease is a women's health issue.
AB  - Alzheimer's disease is not typically included on the list of important women's
      health issues. Yet Alzheimer's disease is indeed a women's disease. Not only do
      more women than men have Alzheimer's disease, but women also provide a
      disproportionate amount of the informal community care for people with the
      disease. The prevalence of Alzheimer's disease increases dramatically with age
      and is highest among those 85 years of age and older. Women make up 72% of the US
      population over age 85 and, therefore, are the group most affected by the
      disease. By the year 2050, the number of people with Alzheimer's disease will
      more than double from approximately 4 million to 10 million, and 70% of these
      people will be age 85 or older. Although the symptoms and course of Alzheimer's
      disease may be similar in women and men, social and economic factors may produce
      a greater burden of disease among women, particularly with respect to the types
      and quality of health care services they receive, because women generally have
      the most limited social and financial resources. As the population ages, typical
      patients with Alzheimer's disease will be much older, frailer, and will have more
      functional impairments and chronic diseases than the patients most physicians see
      today. Future research needs to focus on identifying modifiable risk factors and
      effective treatments for Alzheimer's disease, and on determining the appropriate
      types of community-based and institutional services required to care for those
      with the illness as well as their families.

PMID- 9240003
TI  - Pharmacotherapy for elderly women.
AB  - Age-related physiological changes alter the response of elderly individuals to
      drug therapy, placing them at heightened risk for adverse effects and drug
      interactions. Other factors influencing the therapeutic outcome of drug treatment
      include compliance, self-medication, multiple medications, functional impairment,
      and economics. This article reviews the principles of geriatric pharmacotherapy,
      specifically as they relate to elderly women. Methods to improve the use of
      medications in elderly patients are discussed.

PMID- 9240004
TI  - Elder mistreatment: its relevance to older women.
AB  - Elder mistreatment, both abuse and neglect, is an important health care problem
      for women since they are involved as victims and as perpetrators. The incidence
      of both forms of such mistreatment is increasing, and both often occur within the
      context of long-term care. Elder abuse occurs in both unidirectional and dual
      directional forms, and includes parent abuse and spouse abuse. Elder neglect
      occurs in two forms; neglect by others and self-neglect. While elderly men and
      women are both neglected and/or abused, women may suffer greater physical and
      psychological consequences. To date, researchers have inadequately addressed the
      relevance of gender to both forms of elder mistreatment. This literature review
      addresses what is currently known about elder abuse and neglect that is of
      particular relevance to older women.

PMID- 9240005
TI  - End-of-life issues for very elderly women: incurable and terminal illness.
AB  - Important demographic realities may have an impact on a woman's end-of-life
      options. The vast majority of Americans age 85 and older are women, and they are
      much more likely than their male counterparts to be widowed, live alone, live
      below the poverty line, or die in a nursing home. Although pain is not inevitable
      among the terminally ill, it is vastly undertreated, and elderly women are at
      heightened risk for undertreatment. Pain and other physical and psychological
      symptoms should be treated aggressively, according to well-delineated principles
      of palliative care, including avoiding painful, unwanted treatments that only
      serve to prolong the dying process. Patients have the right to refuse unwanted
      treatment, even if this would result in death, and patients who lack decisional
      capacity can refuse these treatments through an authorized surrogate decision
      maker. Formal, written advance directives are particularly important for older
      women, who may be the group least likely to desire life-sustaining treatment.
      Dying patients also have the right to receive adequate analgesia or sedation for
      intractable symptoms, even if it might hasten death. Societal and legal consensus
      has been reached that forgoing treatment and receiving adequate symptom control
      are permissible, while significant moral and legal debate over the permissibility
      of euthanasia and assisted suicide continues.

PMID- 9240006
TI  - Women in US medicine: the comparative roles of graduates of US and foreign
      medical schools.
AB  - The feminization of US medicine has occurred historically through two separate
      phenomena: the increase in the number of female graduates of US medical schools
      and the in-migration of female graduates of foreign medical schools. Reported
      here are the findings regarding gender on specialty choice, employment setting,
      and specialty board certification of 55,031 and 191,723 graduates of foreign
      medical schools and US medical schools, respectively. Graduates of foreign
      schools were subdivided into those who were foreign-national international
      medical graduates (IMGs), naturalized US citizen IMGs, and native-born US citizen
      IMGs at the time of entry into the US medical system. Statistically significant
      differences between women and men as well as among groups of medical graduates
      were found, with women in each medical graduate group proportionately
      overrepresented in primary care specialties, underrepresented in medical and
      surgical specialties, and underrepresented in both solo practice and group
      practice settings. Foreign-national IMG women were especially overrepresented in
      pathology, radiology, and anesthesiology, and in certain employment settings such
      as public hospitals and the Veterans Administration. The findings provide a basis
      for further study of the causes and consequences of the observed differences.

PMID- 9240007
TI  - Azithromycin in the treatment of chlamydial cervicitis and eradication of
      Ureaplasma urealyticum in female lower genital tract.
AB  - From May 1995 to May 1996, thirty-six females with chlamydial cervicitis were
      enrolled at Bangrak Hospital's Venereal Disease Clinic in an open study to assess
      the efficacy and safety of a single, 1-gram oral dose of azithromycin. Thirty
      five had positive C. trachomatis and one had a positive Gen-probe test. Twenty
      two returned for their first and second follow-ups and 18 came back for their
      final follow-up (visit 4). Eradication rate was 100 per cent on all visits.
      Fourteen patients were excluded from the final analysis- three had dropped out
      from the beginning, ten had sexual intercourse without a condom and one had a
      positive Gen-probe test but negative C. trachomatis culture. U. urealyticum was
      isolated from the vaginal wall of 15 of the 36 cases and eradication rate was 0
      per cent at visit 2 and visit 4. In conclusion, this study shows that a single, 1
      gram oral dose of azithromycin is an effective and well-tolerated alternative
      therapy for chlamydial cervicitis.

PMID- 9240009
TI  - Itraconazole for treatment of oral candidosis in pediatric cancer patients.
AB  - Oral candidosis commonly occurs in malignancy children undergoing antineoplastic
      chemotherapy. Inadequate response to antifungal treatment leads to a risk of
      disseminated infection. The aim of this study is to evaluate the efficacy and
      side effects of itraconazole on treatment of oral candidosis. Fourteen children
      with malignancy undergoing chemotherapy received itraconazole 100-200 mg/day for
      10 days to treat oral candidosis. The severity of disease was defined as mild and
      moderate depending on the number of lesions and symptoms. Oropharyngeal lesions
      and symptoms were recorded initially and daily. Blood chemistries were done on
      day 0, day 10 and day 16. The overall response rate was 87.5 per cent. The mild
      group (4 cases) had a response rate of 100 per cent which had lesions and
      symptoms resolved on day 2 and day 1.5 +/- 0.7 respectively. The moderate group
      (10 cases) had 8 responders (80%) whose lesions and symptoms resolved on day 6 +/
      2.5 and day 4.1 +/- 2.3 respectively. Side effects and abnormal blood chemistry
      values. were not seen.

PMID- 9240008
TI  - Shedding of HIV-1 subtype E in semen and cervico-vaginal fluid.
AB  - The uneven expansion of HIV-1 subtypes in each transmitted group raises the
      possibility that some viruses have less/more potential by
      qualitative/quantitative for heterosexual transmission compared to others. In
      Thailand, HIV-1 subtype E is mainly spread via heterosexual route and accounts
      for about 95 per cent of the infected cases. To determine whether high sexual
      infectivity of HIV-1 subtype E is due to the presence of a virus in genital
      fluid, we conducted a study to characterize shedding of HIV-1 in seminal and
      cervico-vaginal fluids of 30 HIV-1 subtype E infected Thai couples by PCR and
      virus isolation methods. All subjects had no HIV-associated diseases and other
      sexually transmitted diseases. HIV-1 subtype E DNA was detected in 22/30 (77.33%)
      of cervico-vaginal and also 22/30 (77.33%) of seminal fluid samples. The
      isolation rate of HIV-1 from semen and cervico-vaginal secretion was 36.67 per
      cent and 16.67 per cent, respectively. Number of HIV-1 subtype E DNA copies in
      the blood is reversely correlated with the number of blood CD4+ T cells, while
      that in genital fluid was not related to CD4+ T cell count. An increase in
      shedding of HIV- DNA subtype E in female genital tract compared to other HIV
      subtypes reported by other investigators might be one reason to explain the rapid
      spread of subtype E by heterosexual transmission in Thailand.

PMID- 9240010
TI  - Prevalence of abnormal glucose tolerance in Khon Kaen Province and validity of
      urine stick and fasting blood sugar as screening tools.
AB  - Three hundred and fifty-five individuals, 152 males and 203 females, aged between
      30 and 74 years, were randomly selected in a two stage selection process from
      rural communities in three districts of Khon Kaen Province, Northeast Thailand.
      The prevalence of impaired glucose tolerance (IGT) and non-insulin dependent
      diabetes mellitus (NIDDM) in the rural area of Northeast Thailand were measured.
      In addition, the validity of the urine stick and fasting blood sugar as screening
      tools against the two hours glucose loading test as golden standard were
      determined. The survey was conducted in July 1995. The glucose loading test was
      performed on 277 individuals. IGT and NIDDM were classified according to current
      World Health Organization suggestions. Prevalence rates for IGT were 18.1 per
      cent and for NIDDM 11.9 per cent. No difference was found between males and
      females, also when controlled for age. NIDDM prevalence increased with age but
      IGT rates already were high in the younger age groups. This finding suggests that
      IGT precedes NIDDM in Thailand. The validity of the urine stick as a screening
      tool in communities was insufficient, with a sensitivity of less than 20 per
      cent. When using fasting blood sugar as a screening test, the sensitivity was
      close to 44 per cent and the specificity 90 per cent. It is concluded that the
      urine stick is not a useful screening tool and the method of using blood sugar
      concentrations for screening have to be improved before it can be applied within
      communities.

PMID- 9240011
TI  - Plasma lipid peroxide and antioxidant levels in diabetic patients.
AB  - The present study was to investigate the levels of plasma lipid peroxide products
      including malondialdehyde (MDA) and conjugated dienes (CD), and antioxidants
      including enzyme superoxide dismutase, glutathione peroxidase, catalase, plasma
      vitamin E and vitamin C in diabetic patients. Fifty-eight diabetic subjects; 16
      males and 42 females, aged 30-75 years, were recruited. Eighteen of them had
      diabetes and forty of them had diabetes with hyperlipidemia. Twenty-seven healthy
      subjects, 8 males and 19 females, aged 30-75 years, were used as the control
      group. The results showed that the concentrations of plasma MDA in diabetic
      patients with or without hyperlipidemia tended to be increased when compared to
      the controls but there were no significant differences. The CD values were
      increased significantly in both diabetic groups when compared with control
      subjects. Significantly elevated levels of plasma MDA and CD were found in
      diabetic patients with hypertriglyceridemia (> 150 mg%). This increment did not
      change the antioxidant status in both enzymes and vitamins except that the plasma
      vitamin E levels and the ratios of tocopherol: cholesterol were increased
      significantly. An increase of lipid peroxide in plasma may be one important
      factor in the development of vascular complication and atherosclerosis seen in
      diabetic patients.

PMID- 9240013
TI  - Bone loss in oophorectomized Thai women.
AB  - This prospective analysis was done in 95 postmenopausal women to observe bone
      loss rate between 59 natural and 36 surgical menopausal women with or without
      hormonal replacement therapy (HRT). Bone mass measurement was performed at lumbar
      spines (L1-L4) and hip by dual energy X-ray absorptiometer at 0, 6 and 12 months.
      The results revealed that in the non-HRT group there was significant faster bone
      loss rate of lumbar spines (LS) and hip (H) of the surgical group at 12 months
      (Natural group: LS = -1.11%, H = +2.38%; Surgical group: LS = -4.51%, H = -0.66%,
      P < 0.05). However, there was no significant difference in bone changes of lumbar
      spines and hip between natural and surgical group with HRT at 12 months (Natural:
      LS = +2.0%, H = +4.06%; Surgical: LS = +0.62%, H = +2.28%, P > 0.05). This
      observation showed that without HRT oophorectomized women had greater magnitude
      of bone loss than women who entered menopause naturally.

PMID- 9240012
TI  - Effect of severity of pulmonary disease on nitrous oxide washin and washout
      characteristics.
AB  - The influence of chronic obstructive pulmonary disease (COPD) on the nitrous
      oxide (N2O) washin and washout characteristics was evaluated in 90 (ASA II-III)
      males undergoing elective peripheral surgery under general anaesthesia with
      controlled ventilation. Patients were classified by preoperative bedside
      pulmonary function testing into three groups. Group I (n = 30), patients without
      COPD (FEV1/FVC > 80% predicted values; control group); Group II (n = 30),
      patients with mild COPD (FEV1/FVC = 65-79% of predicted values); and Group III (n
      = 30), patients with moderate COPD (FEV1/FVC = 50-64% of predicted values). The
      anaesthetic technique was standardized for all patients. The Datex Capnomac
      Ultima monitor was used to measure the inspired and expired concentrations of
      nitrous oxide (N2O), carbon dioxide (CO2), and isoflurane. The duration of both
      N2O washin (time from start of N2O administration to equilibrium of inspired and
      expired N2O concentrations) and 5 per cent washout (time from discontinuation of
      N2O to an expired N2O concentration of 5 per cent of the equilibrium value) were
      recorded. The duration of N2O washin and washout were significantly prolonged in
      Groups II and III (P < 0.001) as compared to the control group (Group I). The end
      tidal CO2 concentration decreased significantly during N2O washout without
      causing oxygen desaturation (SpO2 < 90%). We conclude that the duration of N2O
      washin and washout were significantly prolonged in anaesthetized patients with
      COPD which may delay the induction and recovery from N2O anaesthesia.

PMID- 9240014
TI  - Coverage of public reimbursement scheme for traffic accident victims in Thailand.
AB  - Traffic injury is a major threat to public health. Loss of lives and property due
      to traffic accidents raise concern not only among the public but also the
      government. As a result, the Motor Vehicle Accident Victim Protection Act was
      enacted in order to provide compensation for traffic accident victims and their
      relatives in 1992. Three years after the Accident Victim Protection Act came into
      effect, this study, through telephone survey, revealed that less than 10 per cent
      of traffic accident victims were reimbursed for medical care cost by the law. The
      process of reimbursement was found to be cumbersome. In addition, only 18 per
      cent of motor vehicles were found holding insurance policies as required by the
      law.

PMID- 9240015
TI  - Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the
      larynx.
AB  - A moderately differentiated neuroendocrine carcinoma or atypical carcinoid of the
      larynx occurred in a 68-year-old woman who developed rapidly progressive
      dysphagia, hoarseness and a neck mass. Immunohistochemical and electron
      microscopic studies verified the nature of this tumor. Local invasion and distant
      metastases are common. It is suggested that cigarette smoking could increase the
      risk of developing this neoplasm.

PMID- 9240016
TI  - Familial paroxysmal dyskinesia.
AB  - Familial paroxysmal dyskinesia is characterized by recurrent episodic dystonia
      and/or choreoathetosis with totally quiescent intervening periods. It is an
      autosomal dominant with variable penetrance basal ganglia disorder. An 11 year
      old girl who presented with brief kinesigenic paroxysmal dyskinesia is reported.
      The abnormal movements were dramatically controlled by diphenylhydantoin.
      Spontaneous remission was seen in the elder sister of this family.

PMID- 9240017
TI  - Spontaneous carotid dissection.
AB  - Spontaneous internal carotid dissection typically occurs in young or middle-aged
      patients. It is associated with a high rate of recovery and low mortality.
      Anticoagulant and antiplatelet drugs fail to demonstrate a significant
      improvement when compared with placebo. A 38 year-old woman with spontaneous
      dissection of the internal carotid artery diagnosed by MRI is reported. She had
      an excellent recovery without treatment and no recurrent attack occurred after
      one year of follow-up. The clinical manifestations, diagnostic tests and
      treatment of spontaneous internal carotid disection are briefly reviewed in this
      communication.

PMID- 9240018
TI  - The colic of Devonshire.

PMID- 9240019
TI  - Sylvius and the corner saloon.

PMID- 9240020
TI  - Sports anemia and gastrointestinal bleeding in endurance athletes.

PMID- 9240021
TI  - The surgical treatment of complex gastroesophageal reflux disease.

PMID- 9240022
TI  - Adolescents and alcohol: preventive opportunities for health care providers.

PMID- 9240023
TI  - Cultural factors in eating disorders: a perspective from Singapore.

PMID- 9240024
TI  - Physician, protect thyself: minimizing the risk of employee embezzlement.

PMID- 9240025
TI  - Alcohol involvement in motor vehicle fatalities, 1995.

PMID- 9240026
TI  - William S. Halsted and rubber gloves.

PMID- 9240027
TI  - Revision of the International Health Regulations. Progress Report, July 1997.

PMID- 9240028
TI  - Onchocerciasis. Report from the InterAmerican Conference on Onchocerciasis in
      Oaxaca, Mexico.

PMID- 9240030
TI  - A goal achieved!

PMID- 9240029
TI  - Zoonoses control. Human rabies, Kentucky and Montana, 1996.

PMID- 9240031
TI  - Dieulafoy lesion as a cause of massive gastrointestinal bleeding.
AB  - The Dieulafoy lesion, also referred to as exulceratio simplex, caliber-persistent
      artery anomaly, or cirsoid aneurysm, is a relatively rare, yet possibly fatal
      cause of gastrointestinal bleeding. Recent journal articles suggest that this
      pathological entity is not as uncommon as once thought. Advances in endoscopic
      technique and esophagogastroduodenoscopy (EGD) have greatly assisted in earlier
      diagnosis and added options to the treatment regimen for this lesion. The
      relationship of this anomaly to possible exsanguination makes it essential that
      both medical and surgical endoscopists be knowledgeable of the anatomy,
      diagnosis, and management of this pathology. Several therapeutic approaches to
      Dieulafoy's lesion are available and are described.

PMID- 9240032
TI  - New dopamine agonists on the horizon.

PMID- 9240033
TI  - Managing established coronary heart disease.

PMID- 9240034
TI  - Pigeon fancier's lung.

PMID- 9240035
TI  - "Non-lethal" weapons: precipitating a new arms race.

PMID- 9240036
TI  - End of life decisions in mentally disabled people.

PMID- 9240037
TI  - Who wants a career in academic medicine?

PMID- 9240039
TI  - Infant mortality falls among Israeli Muslims.

PMID- 9240040
TI  - A quarter of preventable diseases are environmentally caused.

PMID- 9240043
TI  - BMA opposes legalisation of euthanasia.

PMID- 9240044
TI  - Women doctors believe medicine is male dominated.

PMID- 9240045
TI  - DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study.
AB  - OBJECTIVE: To examine any possible links between exposure to DDE (1,1-dichloro
      2,2-bis (p-chlorophenyl)ethylene), the persistent metabolite of the pesticide
      dicophane (DDT), and breast cancer. DESIGN: Multicentre study of exposure to DDE
      by measurement of adipose tissue aspirated from the buttocks. Laboratory
      measurements were conducted in a single laboratory. Additional data on risk
      factors for breast cancer were obtained by standard questionnaires. SETTING:
      Centres in Germany, the Netherlands, Northern Ireland, Switzerland, and Spain.
      SUBJECTS: 265 postmenopausal women with breast cancer and 341 controls matched
      for age and centre. MAIN OUTCOME MEASURE: Adipose DDE concentrations. RESULTS:
      Women with breast cancer had adipose DDE concentrations 9.2% lower than control
      women. No increased risk of breast cancer was found at higher concentrations. The
      odds ratio of breast cancer, adjusted for age and centre, for the highest versus
      the lowest fourth of DDE distribution was 0.73 (95% confidence interval 0.44 to
      1.21) and decreased to 0.48 (0.25 to 0.95; P for trend = 0.02) after adjustment
      for body mass index, age at first birth, and current alcohol drinking. Adjustment
      for other risk factors did not materially affect these estimates. CONCLUSIONS:
      The lower DDE concentrations observed among the women with breast cancer may be
      secondary to disease inception. This study does not support the hypothesis that
      DDE increases risk of breast cancer in postmenopausal women in Europe.

PMID- 9240046
TI  - Case-control study of oestrogen replacement therapy and risk of cervical cancer.
AB  - OBJECTIVE: To examine the relation between use of oestrogen replacement therapy
      and risk of cervical cancer. DESIGN: Case-control study. SETTING: Northern Italy.
      SUBJECTS: 645 women aged 40-75 years with cervical cancer admitted between 1981
      and 1993 to university and general hospitals. The control group consisted of 749
      women aged 40-75 years admitted to the same hospitals with acute conditions
      judged to be unrelated to any of the known or suspected risk factors for cervical
      cancer. MAIN OUTCOME MEASURES: Use of oestrogen replacement therapy and risk of
      cervical cancer. RESULTS: 40 cases versus 86 controls had ever used oestrogens,
      and the corresponding multivariate odds ratio was 0.5 (95% confidence interval
      0.3 to 0.8). The odds ratios of cervical cancer decreased with duration of use,
      being 0.6 (0.4 to 1.1) for less than 12 months' use and 0.5 (0.2 to 1.0) for use
      for 12 months or more compared with never users. The protection tended to be
      somewhat stronger for women reporting first oestrogen use before age 50. The odds
      ratio was 0.9 (0.5 to 1.7) for women who had taken oestrogens within the past 10
      years and 0.4 (0.2 to 0.7) for those who had taken them 10 or more years ago.
      CONCLUSION: These findings suggest that exogenous oestrogens do not increase the
      risk of cervical cancer and may decrease the risk.

PMID- 9240047
TI  - Retrospective study of doctors' "end of life decisions" in caring for mentally
      handicapped people in institutions in The Netherlands.
AB  - OBJECTIVES: To gain insight into the reasons behind and the prevalence of
      doctors' decisions at the end of life that might hasten a patient's death ("end
      of life decisions") in institutions caring for mentally handicapped people in the
      Netherlands, and to describe important aspects of the decisions making process.
      DESIGN: Survey of random sample of doctors caring for mentally handicapped people
      by means of self completed questionnaires and structured interviews. SUBJECTS: 89
      of the 101 selected doctors completed the questionnaire. 67 doctors had taken an
      end of life decision and were interviewed about their most recent case. MAIN
      OUTCOME MEASURES: Prevalence of end of life decisions; types of decisions;
      characteristics of patients; reasons why the decision was taken; and the decision
      making process. RESULTS: The 89 doctors reported 222 deaths for 1995. An end of
      life decision was taken in 97 cases (44%); in 75 the decision was to withdraw or
      withhold treatment, and in 22 it was to relieve pain or symptoms with opiates in
      dosages that may have shortened life. In the 67 most recent cases with an end of
      life decision the patients were mostly incompetent (63) and under 65 years old
      (51). Only two patients explicitly asked to die, but in 23 cases there had been
      some communication with the patient. In 60 cases the doctors discussed the
      decision with nursing staff and in 46 with a colleague. CONCLUSIONS: End of life
      decisions are an important aspect of the institutionalised care of mentally
      handicapped people. The proportion of such decisions in the total number of
      deaths is similar to that in other specialties. However, the discussion of such
      decisions is less open in the care of mental handicap than in other specialties.
      Because of distinctive features of care in this specialty an open debate about
      end of life decisions should not be postponed.

PMID- 9240048
TI  - Who should decide? Qualitative analysis of panel data from public, patients,
      healthcare professionals, and insurers on priorities in health care.
AB  - OBJECTIVE: To explore the arguments underlying the choices of patients, the
      public, general practitioners, specialists, and health insurers regarding
      priorities in health care. DESIGN: A qualitative analysis of data gathered in a
      series of panels. Members were asked to economise on the publicly funded
      healthcare budget, exemplified by 10 services. RESULTS: From a medical point of
      view, both panels of healthcare professionals thought most services were
      necessary. The general practitioners tried to achieve the budget cuts by limiting
      access to services to those most in need of them or those who cannot afford to
      pay for them. The specialists emphasised the possibilities of reducing costs by
      increasing the efficiency within services and preventing inappropriate
      utilisation. The patients mainly economised by limiting universal access to
      preventive and acute services. The "public" panels excluded services that are
      relatively inexpensive for individual patients. Moreover, they emphasised the
      individual's own responsibility for health behaviour and the costs of health
      care, resulting in the choice for copayments. The health insurers emphasised the
      importance of including services that relate to a risk only, as well as
      feasibility aspects. CONCLUSIONS: There were substantial differences in the way
      the different groups approached the issue of what should be included in the basic
      package. Healthcare professionals seem to be most aware of the importance of
      maintaining equal access for everyone in need of health care.

PMID- 9240049
TI  - Genetic linkage of mild malaria to the major histocompatibility complex in
      Gambian children: study of affected sibling pairs.

PMID- 9240051
TI  - Feasibility of screening toddlers for iron deficiency anaemia in general
      practice.

PMID- 9240050
TI  - Antimicrobials for acute otitis media? A review from the International Primary
      Care Network.

PMID- 9240052
TI  - Recent advances. Cardiac surgery.

PMID- 9240053
TI  - ABC of mental health. Schizophrenia.

PMID- 9240054
TI  - The real ethics of rationing.

PMID- 9240055
TI  - Health in China. Traditional Chinese medicine: one country, two systems.
AB  - China is the only country in the world where Western medicine and traditional
      medicine are practised alongside each other at every level of the healthcare
      system. Traditional Chinese medicine has a unique theoretical and practical
      approach to the treatment of disease, which has developed over thousands of
      years. Traditional treatments include herbal remedies, acupuncture, acupressure
      and massage, and moxibustion. They account for around 40% of all health care
      delivered in China. The current government policy of expansion of traditional
      facilities and manpower is being questioned because many hospitals using
      traditional Chinese medicine are already underutilized and depend on government
      subsidies for survival. Research priorities include randomised controlled trials
      of common treatments and analysis of the active agents in herbal remedies. As
      more studies show the clinical effectiveness of traditional Chinese medicine, an
      integrated approach to disease using a combination of Western medicine and
      traditional approaches becomes a possibility for the future.

PMID- 9240056
TI  - First myocardial infarction in patients of Indian subcontinent and European
      origin. Ethnic differences in outcome may be confounded by socioeconomic status.

PMID- 9240057
TI  - First myocardial infarction in patients of Indian subcontinent and European
      origin. Selection of patients may have influenced outcome of study.

PMID- 9240058
TI  - First myocardial infarction in patients of Indian subcontinent and European
      origin. Longstanding high insulin concentrations may play a part in findings in
      Asians.

PMID- 9240059
TI  - First myocardial infarction in patients of Indian subcontinent and European
      origin. Management differed greatly between the two groups.

PMID- 9240060
TI  - Facial disfigurement. Both counselling for patients and education for the public
      are necessary.

PMID- 9240061
TI  - Facial disfigurement. Counselling is important in healing the whole patient.

PMID- 9240062
TI  - Few government forecasts of public expenditure have been realistic.

PMID- 9240063
TI  - Several studies have shown salmeterol to be more potent than salbutamol for
      systemic effects.

PMID- 9240064
TI  - Integration of hepatitis B vaccination into national immunisation programmes.
      Delivering vaccine to infants at risk is complex.

PMID- 9240065
TI  - Integration of hepatitis B vaccination into national immunisation programmes.
      Alternative strategies must be considered before universal vaccination is
      adopted.

PMID- 9240066
TI  - Treatment of postnatal depression. Two weeks of depression may not be long enough
      to exclude spontaneous recovery.

PMID- 9240067
TI  - Treatment of postnatal depression. Additional information would enhance value of
      study.

PMID- 9240068
TI  - Sri Lankan refugees. Ethnic cleansing is in progress.

PMID- 9240069
TI  - Sri Lankan refugees. Tamils have become soft targets.

PMID- 9240070
TI  - Sri Lankan refugees. Comments are like those of white South Africans not so long
      ago.

PMID- 9240071
TI  - Sri Lankan refugees. Refugee council's assessment of human rights situation in
      Sri Lanka is accurate.

PMID- 9240072
TI  - Sri Lankan refugees. Government denies legitimate rights of minorities.

PMID- 9240073
TI  - Sri Lankan refugees. Tamils are victims of unjust politics, not economic
      refugees.

PMID- 9240074
TI  - Surgical training. Training must be of highest possible quality.

PMID- 9240075
TI  - Surgical training. Structured training is now being used.

PMID- 9240076
TI  - Image postprocessing and contrast agents in clinical MR imaging--an introductory
      overview.
AB  - Some fundamentals of image processing, its applications to MR imaging, and
      inherent problems are discussed. Processing of contrast-enhanced dynamic imaging
      studies is introduced and some clinical examples explain the applications in
      research and clinical routine.

PMID- 9240077
TI  - Nuclear oncology and the Imagene concept.
AB  - Over the past 2 decades we have witnessed an explosion of new radioisotopic
      tracers aimed at detecting, staging and eventually treating tumors. In fact,
      nuclear oncology has evolved into a field on its own. Aside from aspecific
      radioisotopic tracers such as thallium 201 or gallium 67, clinicians and
      oncologists can now use specific radiolabeled monoclonal antibodies and metabolic
      tracers. In the near future, molecular probes based on the sequencing of the
      human genome with an exquisite specificity should also become available. In this
      article, we shall review the most recent developments in this new field.

PMID- 9240079
TI  - Hyperpolarized gases--a new type of MR contrast agents?
AB  - The nuclear spin polarization of noble gases can be strongly enhanced by laser
      optical pumping followed by electron-nuclear polarization transfer. Direct
      optical pumping of metastable 3He atoms has been shown to produce enormous
      polarization in the order of 0.4-0.6. This is about 10(5) times greater than the
      polarization of water protons at thermal equilibrium used at conventional MR
      imaging. We demonstrate that hyperpolarized 3He gas can be applied to nuclear MR
      imaging of human organs with air-filled spaces. In vivo 3He MR experiments were
      performed in a whole-body MR scanner with a superconducting magnet ramped down to
      0.8 T and at 1.5 T using a double resonant Helmholtz coil operating at 63.6 and
      48.6 MHz for 1H and 3He, respectively. Anatomical details of the lungs of a
      volunteer were visualized with the FLASH technique demonstrating the potential of
      the method for fast imaging of airways in the human body and for pulmonary
      ventilation studies.

PMID- 9240078
TI  - The synchrotron beam, a new dimension for contrast media research?
AB  - Synchrotron sources can provide intense, collimated and tunable X-ray beams
      suitable for medical imaging and research, allowing the use of monochromatic X
      rays for human examinations. At the European Synchrotron Radiation Facility
      (ESRF), a beam line dedicated to medical research is under commissioning. Two
      imaging programs are being developed, for coronary angiography and cerebral CT.
      The new monochromatic imaging systems should improve image contrast and provide
      better image quantification. The properties of synchrotron radiation are
      described, as well as the instrumentation of the medical beam line and its 2
      imaging programs. The new possibilities offered by synchrotron radiation for
      contrast media research are discussed, the improvement on concentration
      measurement precision achievable is underlined.

PMID- 9240080
TI  - Contrast-enhanced lymphography. CT or MR imaging?
AB  - Lymphography is the radiological visualization of the lymph vessels and lymph
      nodes with contrast material. History and different modes of visualization are
      compared.

PMID- 9240081
TI  - Interstitial MR lymphography using Gd-carrying liposomes.
AB  - The detection of metastasis in lymph nodes is greatly enhanced by the use of
      contrast media. Interstitial injection of lymphography contrast agents requires
      only injection of a low dose of the agent, and leads to high accumulation in
      regional lymph nodes with only minor side effects. We were able to show the
      suitability of liposome-encapsulated gadobutrol as an interstitially injectable
      lymphography contrast agent in an experimental animal model. For screening of
      possible lymphotrophic compounds a guinea pig model was used. Accumulation of the
      contrast agent in 3 successive lymph node groups was determined 4 h after
      subcutaneous injection of the contrast agent (about 0.1 ml of a 30 mmol Gd/l
      solution resulting in a total dose of 10 mumol/kg) into the interdigital skin
      fold of a hind limb. The Gd concentration in the first lymph node group
      (popliteal) was 540 mumol/l (16% dose/g tissue), in the second group (inguinal):
      260 mumol/l (8% dose/g tissue), and in the third group (iliac): 910 mumol/l (27%
      dose/g tissue). Moreover, this compound was completely eliminated and well
      tolerated.

PMID- 9240082
TI  - Contrast-enhanced MR angiography. Methods, limitations and possibilities.
AB  - Whereas conventional MRA relies on enhanced blood signal from flow-induced
      magnitude and/or phase effects, gadolinium-enhanced MRA relies mainly on the
      enhanced blood signal caused by the reduced relaxation time T1. This has a large
      impact on the imaging technique used, as well as on the imaging volume
      orientation and the total scanning time. In general, gadolinium-enhanced MRA is
      faster, with fewer artifacts than MRA without contrast agents.

PMID- 9240083
TI  - Long circulating superparamagnetic particles with high T2 relaxivity.
AB  - Novel superparamagnetic particles coated with a phospholipid and a surfactant
      were characterized and evaluated in vivo. These particles (SBPA) were shown to
      exhibit r2 relaxivities in the range of 350-450 mM-1.s-1, r1 values of 8-12 mM
      1.s-1 and sizes of 50-80 nm. Preliminary results of pharmacokinetics were
      obtained in rats following the administration of 59Fe-labelled preparations. The
      particles were shown to remain for hours in the blood stream before being cleared
      mainly by the liver. Most of 59Fe was eliminated from the body and recovered in
      the feces within a week. These biodistribution and elimination properties deserve
      more detailed studies and suggest the potential use of this product as a blood
      pool contrast agent.

PMID- 9240084
TI  - Characterization of polyethyleneglycol-stabilized, manganese-substituted
      hydroxylapatite (MnHA-PEG). A potential MR blood pool agent.
AB  - PURPOSE: To optimize the performance (or efficacy) of a potential particulate
      blood pool agent for MR angiography by varying the particle size. The colloidal
      system under investigation was polyethylene glycol-stabilized manganese
      substituted hydroxylapatite (MnHA-PEG). MATERIAL AND METHODS: Several MnHA-PEG
      formulations were prepared using various length PEGs (MW = 140-2000). Products
      were characterized in vitro by dynamic light scattering (DLLS), field flow
      fractionation (FFF), and relaxometry; and in vivo by blood clearance kinetics in
      rabbits, and by analytical electron microscopy (EM). RESULTS: The particle size
      distribution (PSD) consisted only of small particles (approximately 10-nm
      diameter) when approximately 40 mo1% PEG was used. At approximately 20 mo1% PEG,
      larger particles (approximately 100 nm), which are aggregates of the small ones,
      were also present. The water proton relaxation profiles of the particles in
      plasma were different from that of the free Mn2+. In plasma, the large aggregates
      were broken down into the smaller particles which were stable. Although the small
      particles were efficient relaxation enhancing agents, they were cleared from the
      blood approximately 3 times faster than the approximately 100-nm diameter
      aggregates, probably as a consequence of leakage into the extravascular space.
      Variation of PEG size had no effect on particle characteristics or on blood
      clearance. Analytical EM of rabbit liver specimens indicated some retention of Mn
      in mitochondria at the time point when Mn content of other subcellular structures
      returned to baseline. CONCLUSION: DLLS and FFF are complementary techniques for
      sizing particulate MR contrast media. Small MnHA particles are more efficient T1
      shortening agents than large ones but they are prone to leakage from the vascular
      space. Within the MW range explored, the length of PEG molecule had no effect on
      blood clearance of the MnHA particles. Larger aggregates of MnHA-PEG break down
      into stable small particles in plasma. Mn clears from the subcellular structures
      within hepatocytes within 60 min after i.v. MnHA-PEG administration except from
      the mitochondria in which it appears to accumulate.

PMID- 9240085
TI  - Myocardial perfusion by contrast-enhanced echocardiography and dynamic contrast
      enhanced MR imaging.
AB  - The evaluation of myocardial perfusion is of clinical relevance in ischemic heart
      disease. New noninvasive and nonionizing imaging techniques for the evaluation of
      myocardial perfusion are progressing. The present status and the future
      development of echo-contrast and dynamic-contrast MR imaging are discussed for
      myocardial perfusion studies.

PMID- 9240086
TI  - Evaluation of hydroxyethyl-starch-ferrioxamine as an intravascular MR contrast
      agent for assessment of myocardial perfusion.
AB  - PURPOSE: The present study was carried out to evaluate a new intravascular
      contrast agent hydroxyethyl-starch-ferrioxamine (HES-FO) for assessment of
      myocardial perfusion. MATERIAL AND METHODS: Isolated pig hearts were perfused
      with a crystalloid cardioplegic solution in a Langendorff apparatus. MR images
      were acquired along the short cardiac axis using T1- and T2*-weighted methods. Gd
      DTPA and HES-FO were used as the standard extracellular and test contrast agents,
      respectively. RESULTS: We found that T1-weighted signal intensity was not
      significantly affected by HES-FO, but increased significantly in presence of Gd
      DTPA. On the other hand, HES-FO resulted in a rapid, transient but significant
      decrease in T2*-weighted signal intensity. Although Gd-DTPA also decreased T2*
      weighted signal intensity considerably, it took much longer for the T2*-weighted
      signal intensity to return to its initial steady-state with Gd-DTPA than with HES
      FO. Moreover, increasing the dose of HES-FO (from 0.0023-0.0138 mmol/kg b.w.) had
      no effect on the time at which the T2* effect reached its maximum or on the
      duration of the T2* effect. However, these times and durations were affected
      significantly by increasing the dose of Gd-DTPA (0.0023-0.027 mmol/kg b.w.).
      CONCLUSION: The results suggest that HES-FO provides information regarding
      myocardial vascular flow which cannot be obtained using Gd-DTPA. It is expected
      that the combined use of intravascular and extracellular type contrast agents
      will allow more complete assessment of tissue perfusion.

PMID- 9240087
TI  - Physical, chemical and biological evaluations of CMD-A2-Gd-DOTA. A new
      paramagnetic dextran polymer.
AB  - PURPOSE: We investigated the synthesis and physical, chemical and biological
      characterisation of a carboxymethyl-dextran polymer substituted with the
      paramagnetic macrocyclic complex Gd-DOTA using an amino spacer. MATERIAL AND
      METHODS: The product was synthesised in 4 steps. Using rigorous purification
      conditions in each step, a polymer was obtained, i.e. CMD-A2-Gd-DOTA, whose
      polydispersity profile was comparable to the initial dextran (I = 1.66-Mw = 50.5
      kDa). Approximately 22% of the glucose groups were replaced by Gd-DOTA and 39%
      were replaced by carboxyl groups. The paramagnetic efficacy of the polymer was 3
      times higher than Gd-DOTA alone, which suggests that the injected doses of
      Gd(III) can be reduced. The vascular residence time of the polymer was measured
      in rats and rabbits, showing that the pharmacokinetics of the product is similar
      whatever the dose. Forty-five percent of the product was excreted in urine after
      24 h and 1.64% was found in the liver. No acute toxicity was observed at the
      maximum dose injected (> 5 mmol Gd/kg) and the general biocompatibility of the
      product tested in vitro was comparable to that of Gd-DOTA. RESULTS AND
      CONCLUSION: These results show the advantages of using paramagnetic macrocyclic
      complexes in the synthesis of macromolecules to preserve biological stability, in
      contrast with linear chelates. Additional studies will be carried out to
      demonstrate the benefits of this type of product, particularly in functional
      imaging.

PMID- 9240088
TI  - Ultrasound contrast agents. Examples of blood pool agents.
AB  - PURPOSE: The concept of contrast agents has been extended to ultrasonography (US)
      almost 30 years ago. Due to technical limitations, the development of US contrast
      agents (USCA) was slow until the last decade. The ideal USCA should be nontoxic,
      i.v. injectable, capable to cross the pulmonary capillary bed after a peripheral
      injection, and be stable enough to achieve enhancement for the total duration of
      the examination. It should provide not only Doppler but also B-mode enhancement,
      at a reasonable cost. The efficacy of the most advanced USCA has been reviewed.
      RESULTS AND CONCLUSION: Doppler examinations improved in cases of deep or small
      vessels, vessels with low or slow flow, or vessels studied with a bad insonation
      angle. USCA also enhanced detection of flow within normal and abnormal vessels,
      including tumor and stenotic vessels. Ischemic areas were better delineated.
      Specific settings and software developed by US equipment manufacturers and US
      sequences (such as second harmonic imaging or transient imaging) prefigured the
      necessary adaptation of US units to the new potentials of USCA. Second harmonic
      properties will improve detection of smaller vessels including neovascularization
      associated with tumors. Targeting possibilities will increase the efficacy of
      USCA, and allow specific delivery of active drugs such as anticoagulants or
      cytotoxic compounds. New generations of USCA appear very promising, and are
      becoming part of the US future.

PMID- 9240089
TI  - Targeting of ultrasound contrast material. An in vitro feasibility study.
AB  - PURPOSE: It would be beneficial to design a targetable microbubble ultrasound
      contrast agent that would selectively bind to the areas of interest in the body
      and enhance the target organ in the ultrasound examination. MATERIAL AND METHODS:
      We have studied the feasibility of targeting in a model system. We used avidin
      and biotin as a model ligand-receptor pair. Avidin was adsorbed on the surface of
      polystyrene, and biotin derivative was attached to microbubble shells. After
      removal of unincorporated biotin from the microbubbles, they were allowed to come
      in contact with avidin-coated or albumin-coated plastic. Unbound bubbles were
      washed by a stream of water. RESULTS: Binding of microbubbles to the surface
      occurred selectively in the areas where avidin layer was deposited. Binding of
      microbubbles to avidin layer was dependent on the amount of biotin incorporated
      in the microbubble shell. Presence of free biotin blocked targeting completely.
      Acoustic studies were performed using a custom-built ultrasound measurement
      apparatus and an ultrasound medical imaging system. Microbubble-coated areas of
      the plastic dish were clearly visualized with ultrasound imaging. A strong
      backscattered signal was obtained for microbubble surface densities as low as 3%.
      CONCLUSION: Microbubbles have been selectively targeted via a ligand-receptor
      system in vitro. Firm binding of microbubbles to avidin-coated surface has been
      achieved. Microbubbles deposited on the target were visualized with ultrasound
      imaging systems.

PMID- 9240090
TI  - Alteration of electronic relaxation in MR contrast agents through de-novo ligand
      design.
AB  - The longitudinal electronic state lifetime of the paramagnetic Gd metal within a
      macrocyclic ligand core can be increased by designing ligand frames that alter
      the vibronic interactions between the ligating atoms and the metal. We conducted
      the first pulsed EPR studies that demonstrated the increase in the longitudinal
      state lifetimes of the electronic subsystem at cryogenic temperatures. We also
      designed a simple sucrose/ water model that significantly increases the
      rotational correlation time in solution of the Gd chelate. This model system
      enables relaxivity studies at ambient temperatures that more readily interrogate
      exchange and electronic contributions to the inner-sphere relaxivity by
      effectively removing the rotational correlation time contribution. These results
      combined with water residence (Q) measurements suggest that rigidification of the
      macrocyclic core or that of the pendant arms increases the longitudinal
      electronic state lifetime of the paramagnetic Gd metal. This increased lifetime
      possibly contributes to the improved relaxivity for the rigid Gd chelates
      observed in the sucrose/ water model studies.

PMID- 9240091
TI  - Hepatocyte-directed MR contrast agents. Can we take advantage of bile acids?
AB  - A series of gadolinium complexes conjugated to bile acids was prepared and
      investigated as possible hepatospecific MR imaging contrast agents. In the design
      of such compounds, features such as the nature of the bile acid, the site of
      conjugation on the bile acid skeleton, and the global charge of the conjugate
      were taken into account. Relaxivity measurements carried out in human serum
      indicate interaction of the conjugates with human serum proteins; even small
      structural variations significantly affect relaxivity in human serum.
      Pharmacokinetic data (biliary elimination in the range of 18.4-45.6%) show that
      bile acids can be used as address moieties to transport gadolinium complexes
      through hepatocytes. For a homogeneous series of compounds, differing only in the
      bile acid residue conjugated, it was unexpectedly found that cholic acid is twice
      as efficient an address moiety as cholylglycine or cholyltaurine. Preliminary
      results show that none of the conjugates is transported through the basolateral
      membrane of hepatocytes by the Na+/taurocholate carrier.

PMID- 9240092
TI  - Multinuclear MR characterization of a new hepatobiliary contrast agent.
      Preliminary results.
AB  - PURPOSE: The aim of this work was to characterize the hepatobiliary contrast
      agent Gd-EOB-DTPA in various media: water solution, protein solution,
      phosphorylated metabolite solution, and excised and perfused liver tissue.
      MATERIAL AND METHODS: Different NMR techniques were used: analyses of H-1 NMRD
      profiles, H-2 NMR relaxation rates, O-17 relaxation rates and chemical shifts,
      and P-31 relaxation rates and peak area. RESULTS: The higher proton relaxivity of
      Gd-EOB-DTPA in water as compared to that of Gd-DTPA is due to a smaller distance
      r and to a longer tau R. The kinetic stability of the former compound in ATP
      solution is higher and it forms noncovalent bonds with human serum albumin.
      Internalization of the contrast agent by the hepatocytes does not impair the ATP
      metabolism of the cells but induces relaxation effects on the intracellular
      metabolites of the liver. CONCLUSION: Multinuclear MR studies allow the extensive
      characterization of MR contrast agents in in-vitro and ex-vivo model systems.

PMID- 9240093
TI  - Disparity in cancer survival and alternative health care financing systems.

PMID- 9240094
TI  - Annotation: evaluating OSHA's ethylene oxide standard and evaluating OSHA.

PMID- 9240095
TI  - Topics for our times: the medicine/public health initiative.

PMID- 9240097
TI  - Mammography screening for women aged 40 through 49--a guidelines saga and a
      clarion call for informed decision making.

PMID- 9240096
TI  - Questionable data and preconceptions: reconsidering the value of mammography for
      American Indian Women.
AB  - Although the benefits of mammography are well established, many remain skeptical
      of the value of mammography for American Indian women. This skepticism stems in
      part from a belief that breast cancer is too rare an event among American Indians
      to warrant widespread screening. The validity of this assumption for Northern
      Plains Indians is challenged by a discussion of the limitations of available data
      on breast cancer in American Indian populations (including lack of
      generalizability, underestimation, and an overreliance on relative rather than
      absolute measures of cancer incidence) and by findings from the Minnesota Breast
      and Cervical Cancer Control Program, a federally funded program providing free
      breast and cervical cancer screening to American Indian and other women in
      Minnesota. In light of this information, the authors recommend that the low
      priority of mammography for American Indian women be reconsidered.

PMID- 9240098
TI  - National health care reform and the 103rd Congress: the activities and influence
      of public health advocates.
AB  - OBJECTIVES: This study examined the activities and influence of public health
      interest groups and coalitions on the national health care reform debates in the
      103rd Congress. METHODS: Congressional staff and representatives of public health
      interest groups, coalitions, and government health agencies were interviewed.
      Content analysis of eight leading national health care reform bills was
      performed. RESULTS: The public health community coalesced around public health in
      health care reform; nearly all the major interest groups and government health
      agencies joined two or more public health or prevention coalitions, and half
      joined three or more. The most effective influence on health care reform
      legislation was early, sustained personal contact with Congress members and their
      staffs, accompanied by succinct written materials summarizing key points. Media
      campaigns and grassroots mobilization were less effective. Seven of the eight
      leading health care reform bills included one or more of the priorities supported
      by public health advocates. CONCLUSIONS: The public health community played an
      important role in increasing awareness and support for public health programs in
      the health care reform bills of the 103rd Congress.

PMID- 9240099
TI  - Neighborhood risk factors for low birthweight in Baltimore: a multilevel
      analysis.
AB  - OBJECTIVES: Past research on low birthweight has focused on individual-level risk
      factors. We sought to assess the contribution of macrolevel social factors by
      using census tract-level data on social stratification, community empowerment,
      and environmental stressors. METHODS: Census tract-level information on social
      risk was linked to birth certificate records from Baltimore, Md, for the period
      1985 through 1989. Individual level factors included maternal education, maternal
      age, medical assistance health insurance (Medicaid), and trimester of prenatal
      care initiation. Methods of multilevel modeling using two-stage regression
      analyses were employed. RESULTS: Macrolevel factors had both direct associations
      and interactions with low birthweight. All individual risk factors showed
      interaction with macrolevel variables; that is, individual-level risk factors for
      low birthweight behaved differently depending upon the characteristics of the
      neighborhood of residence. For example, women living in high-risk neighborhoods
      benefited less from prenatal care than did women living in lower-risk
      neighborhoods. CONCLUSIONS: Multilevel modeling is an important tool that allows
      simultaneous study of macro- and individual-level risk factors. Multilevel
      analyses should play a larger role in the formulation of public health policies.

PMID- 9240100
TI  - Evaluating OSHA's ethylene oxide standard: employer exposure-monitoring
      activities in Massachusetts hospitals from 1985 through 1993.
AB  - OBJECTIVES: This study characterized exposure-monitoring activities and findings
      under the Occupational Safety and Health Administration's (OSHA's) 1984 ethylene
      oxide (EtO) standard. METHODS: In-depth mail and telephone surveys were followed
      by on-site interviews at all EtO-using hospitals in Massachusetts (n = 92, 96%
      participation rate). RESULTS: By 1993, most hospitals had performed personal
      exposure monitoring for OSHA's 8-hour action level (95%) and the excursion limit
      (87%), although most did not meet the 1985 implementation deadline. In 1993, 66%
      of hospitals reported the installation of EtO alarms to fulfill the standard's
      "alert" requirement. Alarm installation also lagged behind the 1985 deadline and
      peaked following a series of EtO citations by OSHA. From 1990 through 1992, 23%
      of hospitals reported having exceeded the action level once or more; 24% reported
      having exceeded the excursion limit; and 33% reported that workers were
      accidentally exposed to EtO in the absence of personal monitoring. CONCLUSIONS:
      Almost a decade after passage of the EtO standard, exposure-monitoring
      requirements were widely, but not completely, implemented. Work-shift exposures
      had markedly decreased since the mid-1980s, but overexposures continued to occur
      widely. OSHA enforcement appears to have stimulated implementation.

PMID- 9240101
TI  - The effect of cigarette taxes on cigarette consumption, 1955 through 1994.
AB  - OBJECTIVES: This study examines the effectiveness of state and federal taxes in
      reducing the consumption of cigarettes, estimates the impact of government health
      warnings, and shows how warnings and taxes interact. METHODS: By means of a
      pooled time-series analysis from 1955 through 1994 with the 50 states as units of
      analysis, the impact of excise taxes on cigarette consumption for several
      different models and econometric techniques is assessed. RESULTS: From 1955
      through 1994, increases in state taxes were effective in reducing cigarette use.
      Federal tax increases, however, appear to have been more effective. This
      difference is partly the result of the "bootlegging" of cigarettes across state
      lines and the size of the increases in the federal tax. Cigarette consumption
      also declined when health warning labels were added. CONCLUSIONS: Increases of
      taxes on cigarettes are associated with declines in the consumption of tobacco.
      Because of inflation, increased health concerns, and the declining percentage of
      smokers, however, large reductions in consumption require large tax increases.

PMID- 9240102
TI  - Tobacco and alcohol use behaviors portrayed in music videos: a content analysis.
AB  - OBJECTIVES: Music videos from five genres of music were analyzed for portrayals
      of tobacco and alcohol use and for portrayals of such behaviors in conjunction
      with sexuality. METHODS: Music videos (n = 518) were recorded during randomly
      selected days and times from four television networks. Four female and four male
      observers aged 17 to 24 years were trained to use a standardized content analysis
      instrument. All videos were observed by rotating two-person, male-female teams
      who were required to reach agreement on each behavior that was scored. Music
      genre and network differences in behaviors were analyzed with chi-squared tests.
      RESULTS: A higher percentage (25.7%) of MTV videos than other network videos
      portrayed tobacco use. The percentage of videos showing alcohol use was similar
      on all four networks. In videos that portrayed tobacco and alcohol use, the lead
      performer was most often the one smoking or drinking and the use of alcohol was
      associated with a high degree of sexuality on all the videos. CONCLUSIONS: These
      data indicate that even modest levels of viewing may result in substantial
      exposure to glamorized depictions of alcohol and tobacco use and alcohol use
      coupled with sexuality.

PMID- 9240103
TI  - The use of outpatient mental health services in the United States and Ontario:
      the impact of mental morbidity and perceived need for care.
AB  - OBJECTIVES: This study compared the associations of individual mental health
      disorders, self-rated mental health, disability, and perceived need for care with
      the use of outpatient mental health services in the United States and the
      Canadian province of Ontario. METHODS: A cross-sectional study design was
      employed. Data came from the 1990 US National Comorbidity Survey and the 1990
      Mental Health Supplement to the Ontario Health Survey. RESULTS: The odds of
      receiving any medical or psychiatric specialty services were as follows: for
      persons with any affective disorder, 3.1 in the United States vs 11.0 in Ontario;
      for persons with fair or poor self-rated mental health, 2.7 in the United States
      vs 5.0 in Ontario; for persons with mental health-related disability. 3.0 in the
      United States vs 1.5 in Ontario. When perceived need was controlled for, most of
      the between country differences in use disappeared. CONCLUSIONS: The higher use
      of mental health services in the United States than in Ontario is mostly
      explained by the combination of a higher prevalence of mental morbidity and a
      higher prevalence of perceived need for care among persons with low mental
      morbidity in the United States.

PMID- 9240104
TI  - The distance to community medical care and the likelihood of hospitalization: is
      closer always better?
AB  - OBJECTIVES: This study examined the influence that distance from residence to the
      nearest hospital had on the likelihood of hospitalization and mortality. METHODS:
      Hospitalizations were studied for Maine. New Hampshire, and Vermont during 1989
      (adults) and for 1985 through 1989 (children) and for mortality (1989) in
      Medicare enrollees. RESULTS: After other known predictors of hospitalization
      (age, sex, bed supply, median household income, rural residence, academic medical
      center, and presence of nursing home patients) were controlled for, the adjusted
      rate ratio of medical hospitalization for residents living more than 30 minutes
      away was 0.85 (95% confidence interval [CI] = 0.82, 0.88) for adults and 0.78
      (95% CI = 0.74, 0.81) for children, compared with those living in a zip code with
      a hospital. Similar effects were seen for the four most common diagnosis-related
      groups for both adults and children. The likelihood of hospitalization for
      conditions usually requiring hospitalization and for mortality in the elderly did
      not differ by distance. CONCLUSIONS: Distance to the hospital exerts an important
      influence on hospitalization rates that is unlikely to be explained by illness
      rates.

PMID- 9240105
TI  - Hospital use and health status of women during the 5 years following the birth of
      a premature, low-birthweight infant.
AB  - OBJECTIVE: This study examined the health status and hospital use of women after
      the birth of a premature, low-birthweight infant. METHODS: The subjects were
      women with infants who participated in a multisite, randomized trial of an early
      intervention program. The outcomes examined were (1) a maternal health rating of
      poor or fair (i.e., poorer health) 5 years following delivery and (2) hospital
      use for a non-pregnancy-related condition. RESULTS: By the fifth year after
      delivery, 29.7% of the women had been hospitalized for a non-pregnancy-related
      condition. Women who reported poorer health status (adjusted relative risk [RR] =
      2.39; 95% confidence interval [CI] = 1.86, 3.07) or who had asthma (RR = 2.24; CI
      = 1.31, 3.80) were at greatest risk. After 5 years, 16.9% of the women said they
      were in poorer health. The number of intervening years in poorer health (1 year,
      RR = 3.17; CI = 2.04, 4.94; > 1 year, RR = 8.42; CI = 2.20, 12.88), more than 1
      year of poverty (RR = 3.28; CI = 1.90, 5.66), obesity (RR = 3.30; CI = 1.44,
      7.55), and more than 1 year of employment (RR = 0.55; CI = 0.36, 0.86) were all
      significantly associated with poorer health. CONCLUSIONS: The continued,
      substantial morbidity and hospital use of women with a premature, low-birthweight
      infant has not previously been reported. This observation needs to be verified.

PMID- 9240106
TI  - An international comparison of cancer survival: Toronto, Ontario, and Detroit,
      Michigan, metropolitan areas.
AB  - OBJECTIVES: This study examined whether socioeconomic status has a differential
      effect on the survival of adults diagnosed with cancer in Canada and the United
      States. METHODS: The Ontario Cancer Registry and the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) program provided a total of
      58,202 and 76,055 population-based primary malignant cancer cases for Toronto,
      Ontario, and Detroit, Mich, respectively. Socioeconomic data for each person's
      residence at time of diagnosis were taken from population censuses. RESULTS: In
      the US cohort, there was a significant association between socioeconomic status
      and survival for 12 of the 15 most common cancer sites; in the Canadian cohort,
      there was no such association for 12 of the 15 sites. Among residents of low
      income areas, persons in Toronto experienced a survival advantage for 13 of 15
      cancer sites at 1- and 5-year follow-up. No such between-country differentials
      were observed in the middle- or high-income groups. CONCLUSIONS: The consistent
      pattern of a survival advantage in Canada observed across various cancer sites
      and follow-up periods suggests that Canada's more equitable access to preventive
      and therapeutic health care services is responsible for the difference.

PMID- 9240107
TI  - Survival rates for four forms of cancer in the United States and Ontario.
AB  - OBJECTIVES: In this study, cancer survival rates for patients diagnosed in
      Ontario and selected areas within the United States were compared. METHODS:
      Relative survival rates were computed for patients aged 15 through 84 years
      diagnosed with any of four forms of cancer (breast, colon, lung, and Hodgkin's
      disease). The cohorts represented those diagnosed over the years 1978 through
      1986 in the Canadian province of Ontario and in nine regions covered by the US
      National Cancer Institute's Surveillance Epidemiology and End Results program.
      Patients were followed through the end of 1990. RESULTS: The cumulative relative
      survival rates were similar for American and Canadian patients. The largest
      difference was observed for breast cancer, where patients in the United States
      enjoyed a survival advantage throughout the follow-up period. CONCLUSIONS:
      Patients in the United States and Ontario with the diseases studied, except for
      breast cancer, experience very similar survival. The greater use of mammographic
      screening in the United States could account for that country's higher breast
      cancer survival rate by promoting earlier and therefore more efficacious
      treatment, by introducing bias, or by a combination of both treatment and bias
      factors.

PMID- 9240108
TI  - The association of drinking water source and chlorination by-products with cancer
      incidence among postmenopausal women in Iowa: a prospective cohort study.
AB  - OBJECTIVES: This study assessed the association of drinking water source and
      chlorination by-product exposure with cancer incidence. METHODS: A cohort of
      28,237 Iowa women reported their drinking water source. Exposure to chlorination
      by-products was determined from statewide water quality data. RESULTS: In
      comparison with women who used municipal ground-water sources, women with
      municipal surface water sources were at an increased risk of colon cancer and all
      cancers combined. A clear dose-response relation was observed between four
      categories of increasing chloroform levels in finished drinking water and the
      risk of colon cancer and all cancers combined. The relative risks were 1.00,
      1.06, 1.39, and 1.68 for colon cancer and 1.00, 1.04, 1.24, and 1.25 for total
      cancers. No consistent association with either water source or chloroform
      concentration was observed for other cancer sites. CONCLUSIONS: These results
      suggest that exposure to chlorination by-products in drinking water is associated
      with increased risk of colon cancer.

PMID- 9240109
TI  - An evaluation of educational outreach to general practitioners as part of a
      statewide cervical screening program.
AB  - OBJECTIVES: The purpose of this study was to determine the acceptability,
      effectiveness, and cost of a face-to-face educational outreach intervention in
      the context of a program aimed at increasing cervical screening in Victoria,
      Australia. METHODS: All identified general practitioners in a specified
      intervention area were offered a visit by a general practitioner educator.
      Practitioners completed a questionnaire evaluating the acceptability of the
      visit. Odds ratios for a woman being screened in the 3 months following the
      visits were determined. RESULTS: Fifty-nine general practitioners (69.4%)
      accepted the offer of a visit. Most found both the process and the content of the
      intervention to be acceptable. The intervention and nonintervention regions did
      not differ either before or after the intervention. In both regions, there was a
      statistically significant increase in number of Pap tests performed. There was no
      difference in the change in screening between the two regions. Costs were
      estimated at Au$34 per general practitioner visited. CONCLUSIONS: This strategy
      cannot be recommended for widespread use in a cervical screening program.

PMID- 9240111
TI  - The delivery of preventive services in primary care practices according to
      chronic disease status.
AB  - OBJECTIVES: The current study examined the relationship between chronic disease
      status and the receipt of cancer preventive services over a 3-year period.
      METHODS: Adults (n = 4320) cared for by 167 nonacademic physicians in 42 primary
      care group practices were studied. Medical records were audited for each patient,
      as were patient responses to two questionnaires assessing health and
      sociodemographic characteristics. RESULTS: While the odds of having received
      counseling to obtain regular checkups were increased for men (1.56) and women
      (1.46) with hypertension, the odds were reduced (range = 0.32 to 0.81) for having
      received a sigmoidoscopy (women with diabetes or hypertension, men with
      hypertension or heart disease), fecal occult blood test (men with diabetes or
      heart disease, women with heart disease), mammogram or counseling about smoking
      (women with diabetes), clinical breast exam (women with heart disease), and Pap
      test (women with diabetes or heart disease). CONCLUSIONS: The presence of common
      chronic health problems in older adults is associated with lower levels of cancer
      screening services.

PMID- 9240110
TI  - The costs and effects of cervical and breast cancer screening in a public
      hospital emergency room. The Cancer Control Center of Harlem.
AB  - OBJECTIVES: This study assessed the cost-effectiveness of cervix and breast
      cancer screening in a public hospital emergency room. METHODS: Age-eligible women
      with nonurgent conditions and without recent screening were offered screening by
      a nurse. A decision analysis compared the costs and outcomes of emergency room
      screening and standard hospital screening efforts. RESULTS: The undiscounted cost
      effectiveness results for establishing new programs were $4050 (cervical cancer),
      $403,203 (breast cancer), and $4375 (joint cervix and breast cancer) per year of
      life saved. If screening is added to an existing program, results are more
      favorable ($429, $21,324, and $479 per year of life saved for cervix, breast, and
      joint screening, respectively). Results were most sensitive to volume and
      probability of receiving treatment after an abnormal screen. CONCLUSIONS:
      Emergency room screening was cost-effective for cervical cancer; breast cancer
      screening was relatively expensive given the low number of women reached. More
      intensive recruitment and follow-up strategies are needed to maximize the cost
      effectiveness of such programs.

PMID- 9240112
TI  - State legislators' attitudes and voting intentions toward tobacco control
      legislation.
AB  - OBJECTIVES: This study describes state legislators' knowledge, attitudes, and
      voting intentions with regard to tobacco-related issues. METHODS: A cross
      sectional survey of state legislators was conducted in North Carolina, Texas, and
      Vermont in 1994. RESULTS: Most legislators agreed that secondhand smoke can cause
      lung cancer in nonsmokers, and a majority believed that smokers are addicted to
      nicotine. More than 75% stated that they would support a measure to enforce laws
      preventing tobacco sales to youth. A majority of Texas and Vermont legislators
      supported an increase in the state cigarette excise tax; 43% of North Carolina
      legislators would support an increase if revenues were directed toward tobacco
      farmer diversification. CONCLUSIONS: State legislators believe tobacco to be
      addictive, and they support policies to protect youth from tobacco. Support for
      other legislative measures differs significantly across states.

PMID- 9240113
TI  - A smoking cessation program at a public antenatal clinic.
AB  - OBJECTIVES: A randomized trial evaluated the impact of smoking cessation
      interventions on point prevalence and consecutive quit rates at an Australian
      public prenatal clinic. METHODS: Self-reports and urine cotinine tests confirmed
      patients' smoking status at the midpoint and end of pregnancy and 6 weeks
      postpartum. RESULTS: At all points, validated abstinence rates were significantly
      higher in the experimental group than in the control group. The rate of failed
      biochemical validation was significantly higher in the control group than in the
      experimental group. CONCLUSIONS: Prenatal clinic staff can significantly increase
      quit rates by using cognitive-behavioral strategies. Brief advice appears to be
      ineffective.

PMID- 9240114
TI  - An association between the heat-humidity index and preterm labor and delivery: a
      preliminary analysis.
AB  - OBJECTIVES: The goal of this study was to determine whether a relationship exists
      between heat-humidity indexes and rates of preterm labor and preterm delivery.
      METHODS: Preterm labor and delivery rates were compared during the 2 summer and 2
      winter weeks with the highest and lowest heat-humidity indexes for each season.
      RESULTS: The rate of preterm labor increased consistently from 1.23% to 3.00% as
      the heat-humidity index rose. When preterm births were examined, the trend was
      similar but not statistically significant. CONCLUSIONS: Given the public health
      import of preterm labor and the frequency with which pregnant women may be
      exposed to extremes of heat, studies designed to confirm or refuse our
      preliminary observations are warranted.

PMID- 9240115
TI  - Vaginal douching and adverse health effects: a meta-analysis.
AB  - OBJECTIVES: The meta-analysis described here reviewed the current literature on
      adverse health effects of vaginal douching. METHODS: Papers published in English
      from 1965 through 1995 were potentially eligible. RESULTS: One third of White
      women and two thirds of Black women of reproductive age reported douching
      regularly. Analyses indicated that vaginal douching increases the overall risk of
      pelvic inflammatory disease by 73% and the risk of ectopic pregnancy by 76%.
      Frequent douching was shown to be highly associated with pelvic inflammatory
      disease and modestly associated with cervical cancer. CONCLUSIONS: Current
      literature suggests that frequent douching increases the risk of pelvic
      inflammatory disease, ectopic pregnancy, and, possibly, cervical cancer.

PMID- 9240116
TI  - State-imposed limits on Medicaid reimbursement for nursing facility care.
AB  - OBJECTIVES: Nursing cost-center limits were examined, along with their effects on
      Medicaid. METHODS: A national survey of Medicaid nursing facility reimbursement
      provided data on cost centers for nursing, administration, and capital, whether
      in specific, larger, or multiple cost centers. RESULTS: Most states impose
      nursing and administration limits. Far fewer states impose capital limits, but
      only capital limits may be related to constraint of reimbursement rates.
      CONCLUSIONS: Shifting toward limiting capital costs, or simply eliminating cost
      center limits, might accommodate cost control while removing negative constraints
      on direct resident care.

PMID- 9240117
TI  - Sunbathing habits and sunscreen use among white adults: results of a national
      survey.
AB  - OBJECTIVES: This study assessed current levels of sunbathing and sunscreen use in
      the United States. METHODS: From a general-population telephone survey of aquatic
      activities among adults in 3042 US households, we examined responses by the 2459
      Whites. RESULTS: Most adults (59%) reported sunbathing during the past year, and
      25% reported frequent sunbathing. Of the subsample who reported sunbathing during
      the month before the interview, 47% routinely used sunscreen. Of these
      individuals, almost half did not use sunscreens with a solar protection factor of
      15 or higher. CONCLUSIONS: About a quarter of US White adults report frequent
      sunbathing, and only about a quarter of sunbathers use sunscreens at recommended
      levels. These results should help focus future sun protection educational
      efforts.

PMID- 9240119
TI  - Industrial workers' health and environmental pollution under the new
      international division of labor: the Taiwan experience.
AB  - Using Taiwan as an example, this paper conducts a historical analysis of the
      relationship between economic development in the new international division of
      labor and environmental pollution and industrial workers' health. Three
      industries-asbestos, plastic, and dye-were chosen for case studies. We trace the
      emergence of each industry in Taiwan and study each industry's protection of
      workers' health and environmental quality. Under the new international division
      of labor, the state's prioritization of economic development leads to lenient
      regulation. Under such state policies, employers have few incentives to invest in
      the protection of their workers' health and in the control of environmental
      pollution. Workers and the public are constrained in their efforts to protect
      their own health and prevent environmental pollution. This situation is
      exemplified by the deplorable working conditions and inadequate environmental
      pollution controls in the asbestos, plastic, and dye industries. Workers' health
      and the public's health are greatly compromised by economic development in the
      new international division of labor.

PMID- 9240118
TI  - Socioeconomic status and breast cancer mortality, 1989 through 1993: an analysis
      of education data from death certificates.
AB  - OBJECTIVES: This study examined whether more highly educated women were at
      greater risk of dying of breast cancer during 1989 through 1993. METHODS: Breast
      cancer mortality rates were calculated through death certificates and Current
      Population Survey data. RESULTS: Breast cancer mortality rates were highest among
      women with 12 and with 16 or more years of education. Non-Hispanic Black women
      had the highest mortality rates and Asian women the lowest. Positive
      relationships between mortality and education were found for Hispanic women as
      well as non-Hispanic Black and Asian women. CONCLUSIONS: The previously seen
      positive relationship between breast cancer mortality and education was found
      among US women of color but not non-Hispanic White women.

PMID- 9240120
TI  - Targeted tobacco markets: outdoor advertising in Los Angeles minority
      neighborhoods.

PMID- 9240121
TI  - Learning to recognize scarring among intravenous drug users: a tool for HIV risk
      reduction.

PMID- 9240122
TI  - A shipboard outbreak of tuberculosis in Mississippi and Louisiana, 1993 to 1994.

PMID- 9240124
TI  - Misusing the term 'artificial fluoridation'.

PMID- 9240123
TI  - The adequacy of one sputum smear for diagnosing pulmonary tuberculosis.

PMID- 9240125
TI  - Minimal dissemination of solid epithelial tumours: impact on staging and
      therapeutic strategy.

PMID- 9240126
TI  - The E-cadherin-mediated cell-cell adhesion system in human cancers.

PMID- 9240127
TI  - The referee process of The British Journal of Surgery.

PMID- 9240128
TI  - Functional problems in adult rectal prolapse and controversies in surgical
      treatment.
AB  - BACKGROUND: Rectal prolapse is a condition that has fascinated surgeons for a
      long time. To date, no single ideal surgical treatment has been identified. The
      aetiology of rectal prolapse remains highly controversial, but it is recognized
      that associated functional problems, such as incontinence and constipation, are
      common. The pathophysiology, and controversies surrounding continence and
      constipation, remain topics of debate. METHOD: All relevant papers derived from
      Medline and manual searching on rectal prolapse and associated functional
      problems were reviewed. RESULTS AND CONCLUSION: The surgical management of rectal
      prolapse has evolved from historical encirclement procedures to current minimally
      invasive ones. Successful management must include adequate attention to the
      associated functional problems in order to eradicate the basic abnormality.

PMID- 9240129
TI  - Colour flow duplex imaging of occlusive arterial disease of the lower limb.
AB  - BACKGROUND: The development of duplex ultrasonography and colour flow imaging has
      greatly extended the scope of non-invasive assessment of lower limb arterial
      disease. This review questions whether recent advances might allow colour duplex
      imaging to displace arteriography as the primary imaging modality for native
      vessel occlusive disease. METHODS: A literature review was carried out based
      predominantly on a Medline database search of English language publications from
      1985 to 1996. RESULTS: Increasing evidence indicates that colour duplex
      ultrasonography can accurately image the lower limb native arterial tree, and
      that colour duplex imaging can replace diagnostic arteriography in a large
      proportion of patients. CONCLUSION: Arteriography should no longer be considered
      the gold standard of imaging of peripheral arterial occlusive disease. Future
      studies should concentrate on the efficacy of colour duplex sonography in guiding
      clinical decision making.

PMID- 9240130
TI  - Systemic inflammatory response syndrome.
AB  - BACKGROUND: Localized inflammation is a physiological protective response which
      is generally tightly controlled by the body at the site of injury. Loss of this
      local control or an overly activated response results in an exaggerated systemic
      response which is clinically identified as systemic inflammatory response
      syndrome (SIRS). Compensatory mechanisms are initiated in concert with SIRS and
      outcome (resolution, multiple organ dysfunction syndrome or death) is dependent
      on the balance of SIRS and such compensatory mechanisms. No directed therapies
      have been successful to date in influencing outcome. METHOD: This review examines
      the current spectrum and pathophysiology of SIRS. RESULTS AND CONCLUSION: Further
      clinical and basic scientific research is required to develop the global picture
      of SIRS, its associated family of syndromes and their natural histories.

PMID- 9240131
TI  - Role of endotoxin and nitric oxide in the pathogenesis of renal failure in
      obstructive jaundice.
AB  - BACKGROUND: There is an increased incidence of postoperative renal failure in
      patients with obstructive jaundice. The purpose of this study was to investigate
      the role of endotoxaemia and nitric oxide in this association. METHODS: In bile
      duct-ligated, sham-operated and control rats, plasma total bilirubin levels,
      creatinine clearance and plasma endotoxin were determined. Endothelium-dependent
      vasodilatation to acetylcholine, and endothelium-independent vasodilatation to
      nitroglycerine and forskolin were evaluated in isolated perfused rat kidney.
      RESULTS: Twenty-one of 27 bile-duct ligated rats had endotoxaemia. Plasma
      bilirubin levels were higher and creatinine clearance was significantly reduced
      in the bile duct-ligated endotoxin-positive group compared with values in the
      other groups. Furthermore, in the isolated perfused rat kidney from rats with
      endotoxaemia, basal perfusion pressure and renal vascular relaxation to
      acetylcholine and nitroglycerine which is mediated by guanosine cyclic 3',5'
      cyclic monophosphate (cGMP) were significantly reduced, but relaxation to
      forskolin mediated by adenosine cyclic 3',5'-cyclic monophosphate did not change.
      CONCLUSION: Endotoxaemia in obstructive jaundice may induce overproduction of
      nitric oxide that may lead to impairment of cGMP-associated vasodilatation and
      disrupt autoregulation of the renal vascular bed. This may contribute to renal
      failure in obstructive jaundice.

PMID- 9240132
TI  - Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of
      Vater diagnosed before operation.
AB  - BACKGROUND: Treatment of ampullary adenoma is complicated by difficult
      preoperative staging, malignant potential and a high recurrence rate. This study
      was designed to assess the accuracy of diagnosis and staging by endoscopic biopsy
      and endosonography, and to compare the results of local resection and
      pancreaticoduodenectomy (Whipple procedure). METHODS: All 23 patients, diagnosed
      by endoscopic biopsy and surgically treated by local resection (n = 12) or
      pancreaticoduodenectomy (n = 11) between 1984 and 1994, were analysed
      retrospectively. RESULTS: Pancreaticoduodenectomy was associated with more
      complications (seven of 11 patients versus three of 12) and a longer hospital
      stay (36 versus 18 days) than local resection. After local resection tumour
      excision was incomplete in half of the patients. One patient died after a Whipple
      procedure. Endoscopic biopsy did not identify infiltrating carcinoma in seven of
      the 23 patients. Endoscopic ultrasonography had a 44 per cent accuracy rate for
      tumour invasion and was false positive for lymph node metastases in five of 16
      patients. After local resection one recurrence was observed during follow-up and
      one possibly died from tumour recurrence. CONCLUSION: Diagnosis and staging of
      ampullary adenomas by endoscopic biopsy and endosonography was unreliable. Local
      resection seems a viable alternative for patients whose general condition does
      not allow a Whipple procedure.

PMID- 9240133
TI  - Comparative effects of enteric-coated pancreatin microsphere therapy after
      conventional and pylorus-preserving pancreatoduodenectomy.
AB  - BACKGROUND: A comparative study was performed between patients with exocrine
      pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's
      procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients
      the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and
      their gastric transit time in relation to that of a solid meal were investigated.
      The efficacy of ECPM preparations may differ after Whipple's procedure compared
      with PPPD, because the latter procedure does not include gastrectomy. METHODS:
      Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was
      labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated
      shortly before ingestion to enable imaging with a gamma camera. Intraluminal
      pancreatic enzyme activity was assessed during a 6-h period with two indirect
      tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p
      aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients
      who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake
      meal was not significantly different. The outcome of the indirect pancreatic
      function tests during enzyme supplementation was comparable, and not
      significantly different, from that in healthy volunteers. In patients who had
      PPPD, however, the gastric transit time of microspheres was greatly delayed
      compared with that of the pancake meal (P < 0.05). Improvement in the outcome of
      the indirect pancreatic function tests during enzyme supplementation was much
      less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION:
      In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm
      ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD,
      however, ECPM treatment is often ineffective because the microspheres are
      retained in the stomach. In these patients, use of conventional powdered
      pancreatin enzyme preparations may improve the efficacy of treatment.

PMID- 9240134
TI  - Specimen retrieval in laparoscopic cholecystectomy.

PMID- 9240135
TI  - Outpatient laparoscopic cholecystectomy.
AB  - INTRODUCTION: The results of laparoscopic cholecystectomy performed as an
      outpatient procedure were evaluated in a prospective study. METHODS: Initially,
      only well motivated and healthy patients were offered outpatient laparoscopic
      cholecystectomy. After 50 procedures, all patients referred to the hospital,
      except those with American Society of Anesthesiologists (ASA) grade IV and those
      living alone, were included. Some 200 procedures were studied. RESULTS: Twelve
      patients (6 per cent) were admitted, and 188 (94 per cent) were discharged 4-8 h
      after operation. Fifteen patients (8 per cent) who had early discharge were
      readmitted, nine with complications; in six no complications were documented. The
      frequency of minor complications was 2 per cent and of major complications 5 per
      cent. Some 173 patients who had successful outpatient laparoscopic
      cholecystectomy completed a questionnaire: 164 (95 per cent) characterized their
      experience as excellent, five (3 per cent) as good, two (1 per cent) as
      intermediate and two (1 per cent) as unacceptable. DISCUSSION: This high
      achievement of day-case treatment, even in patients with ASA grade III, is
      explained by a new anaesthetic regimen together with good surgical technique and
      close follow-up.

PMID- 9240136
TI  - Thromboembolism prophylaxis during laparoscopic cholecystectomy.
AB  - BACKGROUND: The aim of this study was to determine current UK practice with
      regard to thromboembolism prophylaxis during laparoscopic cholecystectomy.
      METHODS: Postal questionnaires were sent to 800 members of the Association of
      Surgeons; replies were received from 551 surgeons (69 per cent) of whom 417
      practised laparoscopic cholecystectomy. RESULTS: Heparin was prescribed to all
      patients by 74 per cent, and selectively by 20 per cent, of respondents. Surgeons
      who performed fewer than ten laparoscopic cholecystectomies per annum were
      significantly less likely to use heparin (P < 0.001) and more likely to believe
      that heparin produces significant adverse bleeding (P < 0.01). Thirty per cent of
      respondents used low molecular weight heparin. Stocking to deter thromboembolism
      were used by 74 per cent, and pneumatic compression by 37 per cent. Indications
      for heparin varied considerably and were not influenced by Thromboembolic Risk
      Factors (THRIFT) guidelines. Only 20 per cent of respondents considered that
      thromboembolism was a problem; 91 per cent reported that they had never
      experienced a thromboembolic complication following laparoscopic cholecystectomy.
      CONCLUSION: The rate of thromboembolism after laparoscopic cholecystectomy is
      unknown but most surgeons believe the risk is very low. Surgeons' attitudes
      towards thromboembolism prophylaxis are variable, but most experienced surgeons
      use low-dose heparin.

PMID- 9240137
TI  - Surgical management of pancreatic necrosis presenting with locoregional
      complications.
AB  - BACKGROUND: Local complications of pancreatic necrosis may occur after surgery,
      but when they occur spontaneously render surgical treatment more hazardous and
      impair prognosis. METHODS: A retrospective review was carried out of 83 patients
      who underwent surgery for pancreatic necrosis from 1988 to 1995, to determine the
      incidence, type, treatment and outcome of locoregional complications caused by
      pancreatic necrosis associated with acute pancreatitis. RESULTS: Seventeen
      patients (20 per cent) were identified to have intra-abdominal complications with
      pancreatic necrosis either before operation or at the time of surgery. The
      majority of patients had a delay in intervention (mean 46 days). At presentation
      ten of the 17 patients had one or more organ system failures. Fourteen patients
      had gastrointestinal tract involvement, two had involvement of the biliary tract
      and one patient had a splenic rupture. Six patients died. CONCLUSIONS: In
      patients with pancreatic necrosis, development of locoregional complications is
      associated with a high mortality rate. The presence of gastrointestinal bleeding,
      peritonitis, jaundice or pneumoperitoneum in such patients suggests the presence
      of a complication of the necrotic process and should prompt early intervention.
      Early referral of patients with severe acute pancreatitis to specialized units
      may reduce the risk of locoregional complications.

PMID- 9240138
TI  - Hepatolithiasis associated with cholangiocarcinoma.
AB  - BACKGROUND: Intrahepatic stone is common in East Asia. Hepatolithiasis is a risk
      factor for cholangiocarcinoma but it is difficult to make an accurate diagnosis
      before operation. The effect of intrahepatic stone on diagnosis, treatment and
      survival in patients with coexistent cholangiocarcinoma was investigated.
      METHODS: Between 1981 and 1994, 33 patients with hepatolithiasis and associated
      cholangiocarcinoma were identified and compared respectively to 18 patients with
      intrahepatic cholangiocarcinoma alone. RESULTS: Patients with intrahepatic stones
      had a significantly longer duration of symptoms, a higher frequency of previous
      biliary surgery but a lower rate of preoperative diagnosis. Surgical resection
      was the treatment of choice and was performed in 18 of 33 patients with
      cholangiocarcinoma and stones and in nine of 18 with intrahepatic
      cholangiocarcinoma alone. Significantly inferior 5-year survival rates were found
      in patients with hepatolithiasis: two of 32 versus four of 14 for all cases and
      two of 17 versus four of nine for resectable cases (P < 0.05). CONCLUSION: These
      survival differences may be attributed to delayed diagnosis, lower diagnostic
      rate and relatively fewer curative resections in the patients with stone
      containing cholangiocarcinoma.

PMID- 9240139
TI  - Initial experience with an absorbable laparoscopic ligation clip.
AB  - BACKGROUND: Laparoscopic surgery requires secure and safe methods of ligation and
      haemostasis. This study evaluated the efficacy of an absorbable ligation clip
      with a novel compression closure mechanism. METHODS: A new compression-closure
      absorbable clip was compared with currently available absorbable and non
      absorbable clips used in a variety of laparoscopic procedures in 12 centres
      worldwide. RESULTS: At follow-up to 3 months after the procedure, no
      complications specific to the use of the compression-closure clip were detected.
      Operator satisfaction with the clip was high, with criticism directed at its
      relatively large size. CONCLUSION: This new clip is as safe and effective as
      presently available metal and absorbable clips in providing haemostasis and
      securing tubular structures.

PMID- 9240140
TI  - Long-term survival following resection of colorectal hepatic metastases.
      Association Francaise de Chirurgie.
AB  - AIM: The aim of this study was to analyse characteristics of patients who
      survived more than 5 years after liver resection of colorectal metastases.
      METHODS: A multicentre retrospective study collected 1818 patients who underwent
      curative resection of hepatic metastases between 1959 and 1991. Among the 747
      patients operated on before 1987, 102 survived longer than 5 years, and were
      compared with patients who survived less than 5 years. RESULTS: Three risk
      factors proved independently significant in multivariate analysis between the two
      groups: serosa infiltration (P = 0.003), involvement of peritumoral lymph nodes
      around the primary colorectal tumour (P = 0.04), and a liver resection margin of
      less than 1 cm (P = 0.02). There was no significant difference for other
      parameters studied (location of primary tumour, location, number and size of
      metastases, type of resection). A trend towards a shorter survival of patients
      with increased carcinoembryonic antigen serum level was observed. CONCLUSION:
      Resection of colorectal hepatic metastases can provide long-term survival even in
      patients with poor prognostic factors. It seems justified to undertake resection
      of colorectal liver metastases whenever it may be performed safely as a curative
      treatment.

PMID- 9240141
TI  - Lateral approach to balloon-aided laparoscopic preperitoneal inguinal hernia
      repair.

PMID- 9240142
TI  - Hernia repair in elderly patients.
AB  - BACKGROUND: This study evaluates a 5-year experience of the management of the
      most frequent abdominal wall hernias in an elderly population. METHODS: From
      April 1990 to December 1995, 231 inguinal, 12 femoral and seven umbilical hernias
      were repaired in 221 patients (mean age 74 (range 66-93) years). Concomitant
      diseases were present in 157 patients. A mesh repair was performed with 'tension
      free' or 'plug' techniques in all but 23 inguinal and two femoral hernia repairs,
      in which the Bassini or Shouldice procedures were adopted. Ten emergency hernia
      repairs were performed for strangulation. A total of 232 operations, including
      four emergency hernia repairs, were carried out under local anaesthesia. RESULTS:
      There was no perioperative mortality. Acute intestinal bleeding occurred 2 days
      after surgery in a patient with colonic diverticular disease. Urinary retention
      occurred once following emergency hernia repair under general anaesthesia and
      twice after elective hernia repair under local anaesthesia. Local complications
      included four scrotal haematomas (2 per cent), three wound infections (1 per
      cent) and one case of orchitis with atrophy after repair of a recurrent hernia.
      There was one recurrence after a Bassini repair and one after Shouldice inguinal
      herniorrhaphy. No recurrence was observed after mesh repair. CONCLUSION: Local
      anaesthetic mesh hernia repair is safe and effective in elderly patients. Age
      should be no bar to elective hernia repair. This policy should avoid the
      complications of emergency operation.

PMID- 9240143
TI  - Melanoma of the nose.
AB  - BACKGROUND: Melanoma of the nose is rare and management guidelines are poorly
      defined. In the past, excision margins have often been much narrower than for
      melanoma elsewhere. METHODS: The study was a retrospective clinicopathological
      study of 34 patients with cutaneous melanoma of the nose treated in a single
      unit. RESULTS: Desmoplastic neurotropic melanoma and lentigo maligna melanoma
      were the most common histological tumour types. Local recurrence occurred in
      eight patients, and in six cases appeared to be a result of inadequate excision
      margins. Regional lymph node metastases were associated with a very poor
      prognosis. CONCLUSION: Adequate surgical excision is the mainstay of successful
      treatment for melanoma of the nose. Excision margins for nasal melanoma should
      not be any less than for melanoma elsewhere. Careful planning is required, not
      only to gain local disease control and the best chance of cure, but also to
      achieve functionally and aesthetically acceptable results. Excision margins need
      not be compromised in view of the variety of local flaps that can be employed to
      close the primary defect.

PMID- 9240144
TI  - Pilot study of carotid surgery for acute stroke.
AB  - BACKGROUND: Carotid endarterectomy is usually delayed for 2 months following an
      acute stroke, but the stroke may progress or a further stroke may occur. A
      randomized pilot study of urgent carotid surgery for acute stroke was undertaken
      to assess the feasibility of a definitive multicentre trial. METHODS: Seven
      Manchester hospitals referred patients with acute stroke (less than 7 days
      previously), defined according to the Oxfordshire Community Stroke Project
      classification The carotid arteries were examined by portable continuous-wave
      Doppler ultrasonography. Patients with more than 50 per cent carotid stenosis on
      portable Doppler ultrasonography underwent colour duplex Doppler imaging.
      Patients with more than 70-99 per cent carotid stenosis were randomized to urgent
      carotid surgery or best medical care. RESULTS: A total of 593 patients were
      assessed over 2 years. Of these, 414 had acute stroke, of whom 380 had probable
      cerebral infarction. Complete ipsilateral internal carotid artery occlusion was
      most common in patients with total anterior circulation infarcts (33 (28 per
      cent) of 117), whereas severe ipsilateral (70-99 per cent) stenosis was most
      common in partial anterior circulation infarcts (25 (20 per cent) of 128). Only
      16 patients (one total and 15 partial anterior circulation infarcts) were fit
      enough for surgery and consented to randomization. CONCLUSION: A definitive trial
      of urgent carotid surgery would need to screen large numbers of patients but
      could focus on patients with partial anterior circulation infarcts.

PMID- 9240145
TI  - Cells are present in the smoke created during laparoscopic surgery.
AB  - BACKGROUND: The application of laparoscopy for malignancy has been halted in many
      centres because of a growing number of reports of metastases arising in port
      sites. The smoke created by coagulation during laparoscopic surgery appears to
      contain particles visible to the naked eye. This study tested the hypothesis that
      whole cells can be carried as an aerosol in the pneumoperitoneum during
      laparoscopy. METHODS: Nine patients undergoing laparoscopic surgery for benign
      and metastatic disease were studied. Throughout the procedure the gas of the
      pneumoperitoneum was allowed to escape through a filter. The filters and tubing
      were washed, and washing solution was centrifuged and stained
      immunohistochemically to identify the cells. Three of the filters were also
      examined with an electron microscope. RESULTS: Six of the nine samples contained
      cells. Clumps of whole cells were identified as mesothelial in origin; the
      electron micrographs showed many other cells stuck to the filter, which appeared
      to be blood and mesothelial cells but were not analysed further. CONCLUSION: The
      presence of whole identifiable cells carried in the pneumoperitoneum raises
      concerns for operating staff and could be a mechanism for tumour implantation. No
      malignant cells were found, but ethical considerations prevented intentional
      coagulation of malignant tissue.

PMID- 9240146
TI  - Genetic instability in patients with metachronous colorectal cancers.
AB  - BACKGROUND: Nearly 7 per cent of patients who undergo resection for colorectal
      cancer develop metachronous cancers several years later. A molecular marker that
      could identify patients susceptible to metachronous cancers would be of clinical
      importance. METHODS: Twenty-four colorectal cancers from 15 individuals with
      metachronous colorectal cancer were investigated for microsatellite instability
      at five loci by single stranded conformational polymorphism analysis. A control
      group of 14 colorectal cancers from individuals who had only developed one
      sporadic colorectal cancer each was analysed similarly. RESULTS: Microsatellite
      instability was demonstrated in 17 of 24 cancers from individuals with
      metachronous cancer compared with one of 14 cancers from individuals with a
      single colorectal cancer. CONCLUSION: These results suggest that testing for
      microsatellite instability may be useful in recognizing patients at high risk of
      developing metachronous colorectal cancers.

PMID- 9240147
TI  - Calculi within an anal fistula tract.

PMID- 9240148
TI  - Simultaneous treatment of faecal and urinary incontinence in children with spina
      bifida using double dynamic graciloplasty.

PMID- 9240149
TI  - Timing of operation for appendicitis.

PMID- 9240150
TI  - Tactile feedback in laparoscopic colonic surgery.

PMID- 9240151
TI  - Management of blunt liver trauma in children.
AB  - INTRODUCTION: Management of liver trauma in childhood represents a rare but
      formidable challenge. METHODS: Clinical presentation, grade of liver injury and
      Injury Severity Score (ISS) were studied in 11 cases of blunt liver trauma to
      examine factors influencing outcome. RESULTS: Seven of the 11 children were
      injured severely and had an ISS greater than 16. Seven who were haemodynamically
      stable were treated without operation, but four required surgery for grade III,
      IV and V liver injuries. Two children had primary repair of hepatic lacerations.
      Perihepatic packing was employed in two other cases (grade IV and V injury) for
      uncontrollable haemorrhage. Delayed debridement and thrombectomy plus vena cava
      repair with suturing of liver lacerations in these patients obviated heroic
      efforts at primary repair. Nine children survived. There were two deaths from
      head and neck trauma. DISCUSSION: Selected children with liver trauma can be
      managed non-operatively using established trauma guidelines. Perihepatic packing
      is recommended in unstable patients with complex injuries, followed by delayed
      definitive repair.

PMID- 9240152
TI  - Bilateral laparoscopic adrenalectomy for Cushing's disease.

PMID- 9240153
TI  - Video-assisted distal carotid artery surgery.

PMID- 9240154
TI  - Partial portal arterialization for dearterialized liver after hepatectomy.

PMID- 9240155
TI  - Patterns of lymphatic spread of carcinoma of the ampulla of Vater.
AB  - BACKGROUND: The pattern of lymphatic spread of ampullary cancer is poorly
      documented. This pattern was clarified in order to define the rational extent of
      radical lymphadenectomy. METHOD: Thirty-nine consecutive patients who underwent
      pancreaticoduodenectomy with radical lymphadenectomy were included in the study.
      A total of 1447 lymph nodes dissected from the resected specimens was examined to
      detect the presence of metastatic foci. RESULTS: Twenty-one of the 39 patients
      had a total of 97 positive nodes. The sites of nodal involvement were the
      posterior pancreaticoduodenal (20 of 21 patients), inferior pancreaticoduodenal
      artery (IPDA; 12 of 21), anterior pancreaticoduodenal (three of 21), trunk of the
      superior mesenteric artery (three of 20), pericholedochal (three of 21),
      retroportal (two of 21), and para-aortic (three of five) regions. No metastases
      were found in the hepatic artery, cystic duct, perigastric, right coeliac, middle
      colic artery or right caval node groups. CONCLUSION: Ampullary cancer mainly
      spreads to the posterior pancreaticoduodenal node group, then to the IPDA node
      group, and finally to the para-aortic area. The rational extent of radical
      lymphadenectomy should include the pancreaticoduodenal, superior mesenteric,
      pericholedochal, retroportal and para-aortic nodes.

PMID- 9240156
TI  - Oral erythromycin improves gastrointestinal motility and transit after subtotal
      but not total gastrectomy for cancer.
AB  - BACKGROUND: Erythromycin has been shown to be a powerful prokinetic of the
      gastrointestinal tract. Little is known about its value to improve motility and
      transit in gastrectomized patients. METHODS: Thirteen disease-free patients
      subjected to subtotal gastrectomy and 11 subjected to total gastrectomy for
      gastric cancer entered the study. Gastrointestinal transit of a standard 99mTc
      labelled meal and fasting motility were studied before and after oral
      erythromycin. RESULTS: In patients who had subtotal gastrectomy mean(s.d.)
      gastric half-emptying time was 42(14) min before and 26(11) min after
      erythromycin (P = 0.011). Before erythromycin prolonged rhythmical contractions
      (3 per min) were recorded in eight patients, sporadic non-organized contractions
      in two and prolonged bursts of waves in one. After erythromycin, clustered waves
      resembling a migrating motor complex (MMC) appeared in eight patients, while
      rhythmic motor activity was unchanged in three. In patients who had total
      gastrectomy jejunal half-emptying time was 39(18) min before and 45(12) min after
      erythromycin. In eight patients, frequent MMCs were recorded, peristaltic in
      four, synchronous in one, antiperistaltic in two, with clusters of non-propagated
      waves in one. After erythromycin, longer peristaltic MMCs were recorded in three,
      antiperistaltic MMCs persisted in two, synchronous in one and clusters of non
      propagated waves in two. CONCLUSION: Oral erythromycin improves gastrointestinal
      transit and motility after subtotal gastrectomy. The findings after total
      gastrectomy are controversial.

PMID- 9240157
TI  - Primary retroperitoneal germ cell tumours: excision via a thoracoabdominal
      extraperitoneal approach.
AB  - BACKGROUND: Primary retroperitoneal germ cell tumours usually present as a large
      abdominal mass in young men. The testes are normal on examination and
      ultrasonography but there are usually raised serum levels of human chorionic
      gonadotrophin and/or alpha-fetoprotein. METHODS: Fourteen men (median age 33
      years) with primary retroperitoneal germ cell tumours were treated by
      chemotherapy followed by surgical resection of the primary tumour and metastases
      via a thoracoabdominal extraperitoneal approach. RESULTS: There was minimal
      morbidity. The survival rate was 13 of 14 and the disease-free survival rate was
      11 of 14 after a median follow-up of 15 months. CONCLUSION: The thoracoabdominal
      extraperitoneal approach for the removal of retroperitoneal germ cell tumours and
      their metastases after chemotherapy improves tumour clearance, morbidity and
      recovery time compared with the transperitoneal anterior approach.

PMID- 9240158
TI  - Retroperitoneal endoscopic neurectomy for nerve entrapment after hernia repair.

PMID- 9240159
TI  - Retroperitoneal endoscopic neurectomy for nerve entrapment after hernia repair.

PMID- 9240160
TI  - Prospective randomized trial of clips versus subcuticular polydioxanone for neck
      wound closure.

PMID- 9240161
TI  - Genetic testing is important in families with a history suggestive of hereditary
      non-polyposis colorectal cancer even if the Amsterdam criteria are not fulfilled.

PMID- 9240162
TI  - Extending the role of breast-conserving surgery by immediate volume replacement.

PMID- 9240163
TI  - Extending the role of breast-conserving surgery by immediate volume replacement.

PMID- 9240164
TI  - Osmotic therapy for acute irreducible stoma prolapse.

PMID- 9240165
TI  - High prevalence of Helicobacter pylori infection in duodenal ulcer perforations
      not caused by non-steroidal anti-inflammatory drugs.

PMID- 9240166
TI  - Reduced collagen accumulation after major surgery.

PMID- 9240167
TI  - Ambulatory manometric examination in patients with a colonic J pouch and in
      normal controls.

PMID- 9240168
TI  - Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and
      pN1 lymph node metastases.

PMID- 9240169
TI  - Rectus sheath bupivacaine analgesia after aortic surgery.

PMID- 9240170
TI  - Endorectal repair of rectocoele revisited.

PMID- 9240171
TI  - Long-term urethral catheterization and the urine-biomaterial interface.

PMID- 9240172
TI  - The use of surgical sympathectomy in the treatment of chronic renal pain.
AB  - OBJECTIVE: To assess the efficacy of renal sympathetic denervation in the
      treatment of chronic renal pain. PATIENTS AND METHODS: In a 10-year period, 21
      patients suffering from chronic renal pain underwent 27 renal denervation
      operations, six of which were bilateral. The cause of pain was the loin pain
      haematuria syndrome in 18 patients. RESULTS: Four operations resulted in complete
      pain relief to date (median follow-up 53.5 months). Pain relief after the other
      23 operations in 18 patients lasted a median of 6 months. Assuming that recurrent
      pain was due to neuronal regeneration, nine of the 18 patients with recurrent
      pain underwent a total of 10 re-explorations of the renal pedicle, stripping it
      of all nerve fibres and areolar tissue. Three of these re-explorations produced
      complete pain relief to date (median follow-up 40 months). The median pain-free
      interval of the other seven re-explorations in six patients was 19 months.
      CONCLUSION: Renal denervation cures severe intractable pain in about 25% of
      patients. Recurrence of pain could be prevented in more patients if there was a
      way of preventing re-innervation.

PMID- 9240173
TI  - Is the expression of multidrug resistance gene product a prognostic indicator for
      the clinical outcome of patients with renal cancer?
AB  - OBJECTIVE: To determine the significance of the expression of the multidrug
      resistance gene product (MDR-1) for the aggressiveness of renal cell carcinoma
      (RCC). PATIENTS AND METHODS: The study comprised 31 patients with clinically
      locally confined RCC treated with radical nephrectomy (mean age 64.1 years, range
      41-78; mean follow-up 5.4 years, range 4.3-7.3). Their survival time and disease
      free period were evaluated retrospectively. The expression of the MDR-1 gene
      product was determined immunohistochemically using the JSB-1 antibody in formalin
      fixed paraffin-embedded tumour samples from these patients. The significance of
      this variable and tumour stage and malignancy grade was assessed for predicting
      the survival and disease-free period using Kaplan-Meier plots (log-rank test or
      Tarone's test) and the Cox multiple hazard regression analysis. RESULTS: In a
      univariate analysis, tumour stage (P < 0.002), malignancy grade (P < 0.007) and
      MDR-1 (P < 0.03) were significant prognostic variables for both survival and
      disease-free period. Lower MDR-1 expression was correlated with poorer prognosis.
      On multivariate analysis, MDR-1 and tumour stage were significant factors for
      predicting the disease-free period, whereas tumour stage and malignancy grade
      were the most relevant factors for survival time. Calculating prognostic indices
      based on the results of the Cox analysis, MDR-1 could replace malignancy grade,
      resulting in a better prediction of survival and disease-free period (P < 0.001
      vs 0.0031, P < 0.001 vs 0.021, respectively). CONCLUSION: MDR-1, an established
      predictor for chemo-resistance, may also be a potent prognostic factor for
      outcome in patients with locally confined RCC. Moreover, MDR-1 expression seems
      to correlate with the differentiation of the RCC and thus its value as an
      objective measure of the degree of differentiation should be further explored.

PMID- 9240174
TI  - Prognostic relevance of intracaval neoplastic extension for patients with renal
      cell cancer.
AB  - OBJECTIVE: To assess the diagnosis of vena caval thrombosis (VCT) in patients
      with renal cell carcinoma (RCC) as an independent indicator of prognostic
      importance and when combined with additional tumour characteristics in a
      controlled multivariate analysis. PATIENTS AND METHODS: The clinical course of 53
      patients (41 men and 12 women, mean age 60 years, range 35-79) with RCC and VCT
      was compared with that of a control group of 47 patients (37 men and 10 women,
      mean age 57 years, range 32-76) with RCC but no neoplastic extension into the
      vena cava. RESULTS: With a follow-up of 1-154 months and a mean long-term
      survival of 32 and 35 months, respectively, for patients with and without VCT,
      neither the propagation of the tumour into the vena cava (P = 0.391) nor the
      cranial extension of the thrombosis (P = 0.158) were identified as having any
      prognostic value during univariate or multivariate statistical analysis. The
      presence of regional lymph node (P < 0.001) or distant metastases (P = 0.009) was
      an independent prognostic variable for patients with RCC, with a significant
      decrease in long-term survival (13 and 14 months for patients with lymph node and
      distant metastases, respectively). CONCLUSION: A radical surgical approach is
      essential as standard therapy for the treatment of patients with RCC and
      neoplastic extension into the vena cava. Because they have a significantly
      decreased life expectancy, asymptomatic patients with lymph node or distant
      metastases should be treated conservatively.

PMID- 9240175
TI  - Predictive value of serum immunosuppressive acidic protein for staging renal cell
      carcinoma: comparison with other tumour markers.
AB  - OBJECTIVE: To examine the usefulness of serum immuno-suppressive acidic protein
      (IAP) as a predictor for staging renal cell carcinoma (RCC), using receiver
      operator characteristic (ROC) analysis, and to compare IAP with other tumour
      markers. PATIENTS AND METHODS: From September 1983 to December 1995, serum IAP
      was measured in 133 untreated patients with RCC (mean age 60.1 years, SD 11.4.
      range 31-84). The erythrocyte sedimentation rate (ESR), the levels of fibrinogen,
      C-reactive protein (CRP), and alpha 2-globulin were also measured. To compare
      these markers as predictors of local involvement of the renal capsule, lymph node
      and distant metastasis, the area under the corresponding ROC curve was
      calculated. Tumour size at the time of resection was added in this analysis for
      comparison with the levels of these tumour markers. RESULTS: The final
      pathological stage was T1 or T2 in 101 patients and T3 or T4 in 32, while it was
      N0 in 122 patients, N1-3 in seven, M0 in 114 patients and M1 in 19. The area of
      the ROC curve for tumour size was greatest (0.843) for staging of the local
      extent (T1/T2 versus T3/T4) and that for IAP was 0.714, similar to the values for
      fibrinogen, ESR and CRP. For predicting lymph node metastasis, IAP and fibrinogen
      were the most important (0.864). However, IAP alone (0.894) was the most
      important predictor of distant metastasis. Using an IAP threshold of 600
      micrograms/mL gave a high sensitivity and specificity for detecting lymph node
      and distant metastasis. CONCLUSION: IAP is a valuable predictor of lymph node and
      distant metastasis in patients with RCC, although it is inferior to tumour size
      in predicting local involvement of the renal capsule. The appropriate threshold
      value of IAP for detecting lymph node and distant metastasis is 600
      micrograms/mL.

PMID- 9240176
TI  - The performance characteristics of the bladder tumour antigen test.
AB  - OBJECTIVE: To evaluate the specificity and sensitivity of the Bard bladder tumour
      antigen (BTA) (Bard Inc, Covington, USA) test. PATIENTS AND METHODS: The
      performance of the BTA test was assessed prospectively in 98 patients (30 women
      and 68 men, mean age 64 years, median 67, SD 14.8) undergoing cystoscopy for
      various indications. The urine of the patients was assessed using the BTA test,
      cytology, culture and a dipstick test for haematuria, and the results compared
      with those from cystoscopy as the 'standard'. RESULTS: The overall specificity
      for the BTA test was 79% and the sensitivity 37%. The sensitivity was higher than
      for urine cytology (33%) but less than for the dipstick test (59%). The
      specificity was less than for cytology (100%) but higher than for the dipstick
      test (66%). CONCLUSION: The BTA test is a rapid, non-invasive qualitative test
      identifying degradation products of the basement membrane of the transitional
      cell epithelium. It represents an advance in the search for a 'tumour marker' for
      carcinoma of the bladder. The specificity is acceptable but the sensitivity
      relatively low, which limits its value in everyday practice. Further research and
      development are needed to improve sensitivity.

PMID- 9240177
TI  - Effects of isoniazid on the proliferation and cytokine production of bladder
      cancer cells in vitro induced by bacille Calmette-Guerin.
AB  - OBJECTIVE: To determine the effects of isoniazid (isonicotinic acid hydrazide),
      used to reduce the serious side-effects of immunotherapy of superficial bladder
      cancer with bacille Calmette-Guerin (BCG), on the proliferation and constitutive
      BCG-induced synthesis of interleukins 6 (IL6) and 8 (IL8) in human bladder cancer
      cells cultured in vitro. MATERIALS AND METHODS: Three poorly differentiated human
      cell lines, T24, TCC-SUP and BT-B, were used to study the effect of isoniazid on
      cell proliferation. Cells were inoculated in tissue culture plates and various
      concentrations of isoniazid added to the medium. Cell density was then monitored
      for up to 6 days using a colorimetric assay. To determine the effects of
      isoniazid on constitutive and BCG-induced cytokine synthesis, cells were cultured
      in medium containing no additions, BCG, isoniazid or BCG with isoniazid, at
      various concentrations. Samples of medium were collected regularly for 6 h and
      the cytokine content (IL6 and IL8) determined using enzyme-linked immunosorbent
      assays. RESULTS: Continuous incubation of proliferating T24, TCC-SUP and BT-B
      cells with isoniazid at concentrations of 0-100 micrograms/mL did not affect the
      rate of proliferation. Unlike TCC-SUP and BT-B cells, T24 cells released more IL6
      and IL8 during incubation with BCG. At 6 h after the addition of BCG, the
      cumulative mean (SD) IL6 and IL8 production of T24 cells was 2.6 (0.1) and 2.3
      (0.4) ng per 3 x 10(5) cells, compared with a constitutive level of 0.1 (0.0) and
      1.3 (0.2) ng, respectively. There was no significant effect of isoniazid (1-100
      micrograms/mL) on either the constitutive or BCG-induced synthesis of IL6 and IL8
      in T24 cells. CONCLUSION: Assuming an essential role of (tumour) epithelial cells
      in the local immune response induced by BCG, these in vitro results suggest that
      the administration of isoniazid does not interfere with this part of the
      mechanisms by which BCG operates.

PMID- 9240178
TI  - Lymph-node revealing solution: a new method for detecting minute lymph nodes in
      cystectomy specimens.
AB  - OBJECTIVE: To describe the use of a new lymph-node revealing solution (LNRS) for
      detecting lymph node involvement in total cystectomy specimens from patients with
      locally confined invasive transitional cell carcinoma (TCC) of the bladder, and
      to compare the results obtained with those using the conventional method
      (palpation and sectioning perivesical fat) that may fail to detect very small
      lymph nodes. MATERIALS AND METHODS: Of 12 cystectomy specimens obtained from
      patients with TCC, six in which 0-3 metastatic nodes were identified by the
      conventional method were further investigated using LNRS. The revealing solution
      comprised 95% ethanol, diethyl ether, glacial acetic acid and buffered formalin
      (65:20:5:10 v/v) prepared under a fume-hood. After evaluation using the
      conventional method, the specimens were immersed for 6-12 h in the solution,
      washed under running tap water and the adipose tissue sectioned at intervals of 2
      3 mm. Lymph nodes were identified as white, chalky nodules against the background
      of yellow fat. The number of the lymph nodes identified by conventional and the
      LNRS methods was recorded and classified according the TNM system. RESULT: Twenty
      two lymph nodes were detected by the conventional method, of which four were
      positive for tumour metastasis. Using the LNRS, an additional 21 nodes were
      identified among which 12 were positive. The mean size of the lymph nodes
      detected by the conventional and LNRS methods was 7.96 mm and 3.81 mm,
      respectively. The stage of three patients was increased (Nx to N2, N0 to N2 and
      N1 to N2) and therefore two of these patients received adjuvant chemotherapy.
      CONCLUSIONS: LNRS significantly enhanced the yield of normal and metastatic nodes
      of cystectomy specimens and may identify smaller nodes. The LNRS method allows a
      more accurate staging with better assessment of the prognosis and need for
      adjuvant therapy.

PMID- 9240179
TI  - Combined chemotherapy and radiation with selective organ preservation for muscle
      invasive bladder carcinoma. A single-institution phase II study.
AB  - OBJECTIVE: To assess in a phase II trial the effectiveness and toxicity of
      combined chemotherapy and radiation with selective bladder preservation by
      response in the treatment of muscle-invasive bladder carcinoma. PATIENTS AND
      METHODS: Fifty-six eligible patients with T2-4 M0 transitional cell bladder
      cancer suitable for radical surgery and multi-agent chemotherapy received two
      courses of methotrexate, cisplatin and vinblastine, followed by 40 Gy of pelvic
      radiotherapy in 1.8 Gy fractions with concomitant cisplatin. Tumour response was
      evaluated by cystoscopy and biopsy. Those responding completely were given a 24
      Gy bladder boost plus cisplatin; patients with residual tumour were assigned to
      immediate cystectomy. RESULTS: After induction therapy, 28 patients (50%)
      responded completely; 22 operable patients with residual tumour underwent
      immediate cystectomy, while 34 patients were consolidated with cisplatin and
      radiation. Bladder relapses developed in 16 patients; seven had successful
      endovesical therapy for superficial disease and salvage cystectomy was possible
      in four of nine cases with invasive recurrence. Distant metastases occurred in 22
      cases (39%). After a median follow-up of 46 months, the 5-year actuarial disease
      specific survival was 59%, disease-free survival 54% and local control without
      cystectomy (bladder preservation) 41%. There were no treatment-related deaths;
      grade 3 late complications occurred in two patients. CONCLUSION: This combined
      chemotherapy-radiotherapy regimen with selective organ preservation should be
      considered as an option for muscle-invasive bladder carcinoma. The initial
      results suggest the possibility of retaining a functioning bladder in many
      patients, without compromising survival, compared with elective cystectomy
      approaches. A longer follow-up and quality-of-life assessment remain essential
      for a better definition of selection criteria and long-term results of this
      combined modality.

PMID- 9240180
TI  - Which patients will benefit from psychosocial intervention after cystectomy for
      bladder cancer?
AB  - OBJECTIVES: To investigate: (i) if early psychosocial intervention after
      cystectomy for bladder cancer can assist psychosocial rehabilitation; (ii) if the
      outcome of such intervention correlates with the patient's psychological
      defensive strategies as revealed with the meta-contrast technique (MCT); and
      (iii) if the patient's general philosophical outlook is important in this
      context. PATIENTS AND METHODS: Of 50 patients who had undergone radical
      cystectomy for bladder cancer, 17 received an ileal conduit, 17 a continent
      urinary reservoir with abdominal stoma and 16 an orthotopic neobladder. Twenty
      four of the patients were randomized to psychosocial intervention, comprising
      weekly counselling 4-9 weeks after surgery. All patients were then evaluated with
      the Sickness-Impact Profile (SIP) standard questionnaire and the MCT (a
      projective test of percept-genetic model) was used to reflect individual
      defensive strategies at the subconscious or unconscious level. The patient's
      general philosophical outlook was recorded before and after surgery. RESULTS:
      There was no significant difference in the results of the SIP between the
      intervention and the non-intervention group, as a whole or in its psychosocial
      dimension. However, intervention benefited patients with continent cutaneous
      diversion, whose scores on the psychosocial SIP dimension were lower than in the
      groups with ileal conduit diversion or orthotopic bladder replacement (P < 0.05).
      The MCT analysis of defensive strategies identified three clusters of patients
      characterized mainly by isolation and repression, repression and stereotypy or
      sensitivity and stereotypy. Analysis for cluster identification showed no
      significant SIP score differences between intervention and non-intervention
      groups. In an analysis of single defensive strategies, stereotypy was associated
      with higher total SIP score, but not significantly. Three clusters of
      philosophical outlook were identified; in one cluster, characterized by a belief
      in a supernatural power and philosophical interest, the psychosocial SIP scores
      were lower in the patients who obtained emotional support and the reverse in a
      cluster with contrary attitudes, although neither differences were significant.
      CONCLUSION: Psychosocial intervention assisted the psychosocial rehabilitation of
      patients with continent cutaneous urinary diversion. Defensive strategies and
      philosophical outlook generally did not influence the outcome of intervention.
      However, such programmes may be helpful for some patients, mainly those with a
      basically pessimistic disposition, a general interest in philosophical questions
      and often using defensive strategies of stereotypy and repression.

PMID- 9240181
TI  - Which indwelling urethral catheters resist encrustation by Proteus mirabilis
      biofilms?
AB  - OBJECTIVE: To test the resistance of currently available types of indwelling
      urethral catheters to blockage by encrustation with mineralized Proteus mirabilis
      biofilms. MATERIALS AND METHODS: Encrustation was studied in a simple laboratory
      model of the catheterized bladder. Artificial urine was supplied to the bladder
      chamber at 0.5 mL/min. The bladder urine was inoculated with a clinical strain of
      P. mirabilis that had been isolated from an encrusted catheter. The models were
      operated until the catheters blocked and atomic absorption spectrometry was used
      to assess the amounts of calcium and magnesium deposited on the catheters.
      Scanning electron microscopy was also used to locate and assess the degree of
      encrustation. RESULTS: The mean times to blockage ranged from 21 h for the Bard
      hydrogel/silver-coated latex catheter to 56 h for the Eschmann Folatex S all
      silicone catheter. The calcium and magnesium salts were mainly deposited on the
      10 cm below the eye-holes of the catheters, complete blockage generally occurring
      in the 2 cm immediately below the eye-hole. CONCLUSION: None of the 18 types of
      catheter tested, including those coated with hydrogel or silver, were capable of
      resisting encrustation by P. mirabilis biofilm.

PMID- 9240182
TI  - Glycosaminoglycans in crystal-surface binding substances and their role in
      calcium oxalate crystal growth.
AB  - OBJECTIVE: To clarify the role of glycosaminoglycans (GAGs) in crystal-surface
      binding substances (CSBS) on the growth of calcium oxalate crystals in urine.
      MATERIALS AND METHODS: Urine samples (24 h) were collected from healthy men (aged
      25-42 years) and CSBS were obtained from the pooled urine samples. The CSBS were
      digested with heparitinase or proteinase and the inhibition of crystal growth
      assessed before and after enzyme digestion. Anion-exchange chromatography and
      high-performance liquid chromatography (HPLC) were used to determine the types of
      GAGs contained in the CSBS. RESULTS: The inhibitory activity of CSBS on crystal
      growth decreased with concentration when digested with heparitinase or
      proteinase. HPLC showed that CSBS contained a small amount of dermatan sulphate
      and abundant heparan sulphate, both of which inhibited crystal growth.
      CONCLUSION: Both heparan sulphate and dermatan sulphate may inhibit calcium
      oxalate crystallization, the former being the predominant GAG in CSBS.

PMID- 9240183
TI  - A prospective, randomized, double-blind study comparing lignocaine gel and plain
      lubricating gel in relieving pain during flexible cystoscopy.
AB  - OBJECTIVE: To determine the optimum duration for the retention of 2% lignocaine
      gel intraurethrally as an anaesthetic for flexible cystoscopy in men. PATIENTS
      AND METHODS: A prospective, randomized, double-blind, placebo-controlled trial
      was conducted in two parts. Initially, the importance of duration was determined,
      i.e. whether pain relief was significantly improved when lignocaine gel was
      instilled for longer than is currently practised. As pain relief was improved by
      retaining the lignocaine gel for longer, the optimum time was determined in a
      second trial. Initially, 90 patients were divided into four groups receiving 20
      mL of 2% lignocaine gel or plain lubricating gel for 5 or 25 min. Subsequently,
      60 men were divided into two groups receiving 20 ml of 2% lignocaine gel for 15
      or 25 min. The patients' discomfort was recorded using a 4-point descriptive pain
      scale and a 100 mm non-graphical visual analogue scale. RESULTS: In the first
      study, those patients receiving lignocaine gel for 25 min experienced
      significantly less pain than the other three groups. In the second, lignocaine
      gel in the urethra for 15 min provided the same level of pain relief as
      lignocaine for 25 min. CONCLUSION: Pain during flexible cystoscopy can be
      significantly reduced when 20 mL of 2% lignocaine gel is left in the urethra for
      15 min; lignocaine gel would be more effective when left for longer than is
      currently practised.

PMID- 9240184
TI  - Is obstruction predictable by clinical evaluation in patients with lower urinary
      tract symptoms?
AB  - OBJECTIVE: To determine whether it is possible to predict the presence of bladder
      outlet obstruction (BOO) by non-invasive clinical variables in patients with
      lower urinary tract symptoms (LUTS) suggestive of BOO. PATIENTS AND METHODS:
      Patients with LUTS suggestive of BOO were entered into a prospective protocol
      evaluating the International Prostate Symptom Score (IPSS), prostate size, non
      invasive uroflow, post-void residual urine volume (PVR) and a pressure flow
      study. Only patients with a maximum flow rate (Qmax) of < or = 15 mL/s and an
      IPSS > or = 7 were included. The study comprised 253 patients; the degree of
      obstruction was correlated to several non-invasive clinical variables.
      Subsequently nomograms were developed by multiple logistic regression analysis to
      obtain the probability of BOO in patients with LUTS. RESULTS: Prostate volume,
      Qmax, PVR and voided volume correlated significantly with the degree of BOO rated
      according to the linear passive urethral resistance relation (linPURR). In
      contrast, there was no such correlation for the IPSS and the quality-of-life
      question of the IPSS. The percentage of patients with BOO defined by a linPURR of
      3-6 decreased from 85% in those with a Qmax of 0-5 mL/s to 60% (Qmax 6-10 mL/s)
      and 44% (Qmax 11-15 mL/s). In parallel, the percentage of patients with BOO
      increased from 53% of those with a prostate volume of < or = 50 mL, to 79% of
      those with prostates of 51-100 mL and 75% of those > 100 mL. Based on Qmax, PVR
      and prostate volume, nomograms were established by multiple logistic regression
      analysis for the probability of BOO in patients with LUTS. CONCLUSION: The
      nomograms presented herein should help the clinician to identify patients with
      LUTS who should undergo pressure flow studies before surgical intervention to
      detect the presence of obstruction and in whom these studies can be safely
      spared.

PMID- 9240186
TI  - The correlation between prostate volume, transition zone volume, transition zone
      index and clinical and urodynamic investigations in patients with lower urinary
      tract symptoms.
AB  - OBJECTIVE: To determine if, in patients with lower urinary tract symptoms (LUTS),
      measurement of the transition zone (TZ) of the prostate by transrectal
      ultrasonography (TRUS) and the ratio between the TZ volume and total prostate
      volume (TZ index) correlates better with clinical and urodynamic investigations
      than total prostate volume alone. PATIENTS AND METHODS: In total, 150 consecutive
      patients with LUTS underwent a standardized screening programme including the
      International Prostate Symptom Sore (IPSS), a physical examination, TRUS of the
      prostate and urodynamic investigations with pressure-flow studies. The total
      prostate volume and TZ volume were assessed from TRUS using the ellipsoid
      formula. Spearman's rank correlation coefficients were calculated between
      different prostate volume measurements and specific symptomatic and urodynamic
      variables. RESULTS: The relationships between specific IPSS symptoms, symptom
      scores and the prostate volume measurements were not statistically significant
      except for one domain, nocturia, that appeared to be statistically significantly
      correlated with the TZ index (r = 0.25). The correlations for free flow, pressure
      flow variables and prostate volume measurements were stronger, but only moderate
      at best. The highest correlations were between TZ volume and the linear passive
      urethral resistance obstruction category, urethral resistance factor and detrusor
      pressure at maximum flow (r = 0.43, 0.44 and 0.40, respectively). The differences
      between the correlations of prostate volume and TZ index and these variables were
      small (r = 0.39, 0.38 and 0.37, respectively for prostate volume and r = 0.38,
      0.40 and 0.33 respectively for TZ index). CONCLUSIONS: There were very small
      differences between the correlations of total prostate volume, TZ volume and TZ
      index, and clinical and pressure-flow variables. In the assessment of the last
      two, the estimation of the total prostate volume by TRUS was a reasonable way to
      obtain the required information about prostate size and measuring TZ volume and
      calculating TZ index was of limited additional value. Symptoms and bladder outlet
      obstruction were mainly determined by other factors than the prostate and,
      specifically, TZ volume. As earlier studies have indicated that including
      pressure-flow data in the pre-operative evaluation and selection of patients for
      interventional therapies may improve the overall clinical results, we think that
      prostate volume, TZ volume or symptoms alone should not be used as the main
      indication for deciding on the appropriate invasive treatment options.

PMID- 9240185
TI  - Transition zone ratio and prostate-specific antigen density as predictors of the
      response of benign prostatic hypertrophy to alpha blocker and anti-androgen
      therapy.
AB  - OBJECTIVE: To determine whether transrectal ultrasonography (TRUS) can predict
      the clinical response of patients with benign prostatic hypertrophy (BPH) to
      alpha 1-blocker and anti-androgen therapy. PATIENTS AND METHODS: From April 1994
      to July 1995, 128 patients with BPH were randomized to treatment for 6 months
      with either tamsulosin (a long-acting selective alpha 1-blocker) or allylestrenol
      (an anti-androgen), with 64 patients receiving tamsulosin (0.2 mg/day) and 64
      receiving allylestrenol (50 mg/day). The results of TRUS, uroflowmetry and the
      American Urologic Association (AUA) symptom score were compared before and after
      treatment. TRUS was used to calculate the transition zone (TZ) volume, transition
      zone ratio (TZ ratio = TZ volume/total prostate volume), total prostate volume
      and prostate-specific antigen density (PSAD). RESULTS: Both groups showed a
      statistically significant improvement in the AUA symptom score, quality-of-life
      (QOL) score and peak urinary flow rate (Qmax) at 6 months (P < 0.001). In the
      tamsulosin group, there was a significant negative correlation between the
      pretreatment PSAD and the percentage change in Qmax (r = -0.640, P < 0.001),
      while there was a positive correlation between PSAD and the percentage change in
      the AUA symptom score (r = 0.589, P < 0.001). On the other hand, the
      allylestrenol group showed a significant positive correlation between PSAD and
      the percentage change in Qmax (r = 0.397, P < 0.01) and a negative correlation
      between PSAD and the AUA symptom score (r = -0.313, P < 0.01). CONCLUSION:
      Patients with a high pretreatment PSAD responded well to anti-androgen therapy,
      while those with a low PSAD responded better to alpha 1-blocker therapy.

PMID- 9240187
TI  - How to recognize patients with parkinsonism who should not have urological
      surgery.
AB  - OBJECTIVE: To examine whether there are urogenital criteria that the urologist
      could apply to a patient with idiopathic Parkinson's disease (IPD) and bladder
      symptoms, and so avoid operating on patients with multiple system atrophy (MSA).
      PATIENTS AND METHODS: The clinical features of 52 patients with probable MSA and
      41 patients with IPD were studied retrospectively with particular attention to
      the nature of lower urinary tract symptoms and erectile dysfunction in relation
      to the onset of parkinsonism. Anal sphincter electromyography (EMG) was recorded
      in all the patients with MSA and in 12 of the patients with IPD. RESULTS: Of the
      patients with MSA, 60% had urinary symptoms preceding or presenting with IPD but
      in 94% of the patients with IPD the neurological diagnosis preceded the onset of
      urogenital symptoms. Most of the patients with MSA (73%) had troublesome urinary
      incontinence whereas the majority of those with IPD (85%) had urgency and
      frequency but were not incontinent; 66% of the patients with MSA and 16% of
      patients with IPD had a significant post-void residual volume. Of the men with
      MSA, 93% had erectile dysfunction and in 48% of them this complaint preceded the
      diagnosis of MSA. All 11 men with MSA who had a TURP were incontinent post
      operatively. CONCLUSION: The urogenital criteria which favour a diagnosis of MSA
      are: (i) urinary symptoms preceding or presenting with parkinsonism; (ii) urinary
      incontinence and IPD; (iii) a significant post-void residual urine volume; (iv)
      erectile failure preceding or presenting with parkinsonism; and (v) worsening
      bladder control after urological surgery. Patients with parkinsonism and these
      features should be offered medical management rather than urological surgery.

PMID- 9240189
TI  - Factors influencing blood loss in transurethral resection of the prostate (TURP):
      auditing TURP.
AB  - OBJECTIVES: To assess the blood loss accompanying TURP and investigate its
      association with the resected weight of prostatic tissue, type of anaesthesia,
      type of presentation, histology, different surgeons and their differing
      techniques, and thus to reduce the morbidity associated with blood loss and
      transfusion. PATIENTS AND METHODS: All prostatectomies carried out in a district
      general hospital were audited prospectively, recording the pre- and post
      operative haemoglobin concentration (Hb), blood transfusions and the variables
      listed above. The audit was repeated a year later. RESULTS: The peri-operative
      blood loss, as assessed by various indicators, was equivalent to a decrease in Hb
      of 10-15 g/L (8-11%). The weight of the resected prostatic tissue was the most
      important measurable factor in determining blood loss. Regional anaesthesia was
      associated with less blood loss than general anaesthesia. The added use of a
      suprapubic catheter for irrigation appeared to have a marginal advantage in large
      resections. The type of presentation, elective or otherwise, and the histological
      nature of the prostate did not influence blood loss. Smaller transfusions were
      probably avoidable in patients having smaller resections and a normal pre
      operative Hb. On re-auditing, the overall transfusion rate was reduced from 10.8%
      to 8.2% and from 4.4% to 1% in patients having resections of < 30 g. CONCLUSION:
      Blood transfusion can be reduced and rationalized. Patients with a normal pre
      operative Hb and undergoing resections of < 30 g do not usually require
      transfusion. Regional anaesthesia is associated with less blood loss but its
      advantage is overshadowed in practice by the weight of the resected tissue. An
      audit of this type is repeatable and is useful in raising awareness, objectively
      assessing differences and advocating and assessing any changes made.

PMID- 9240188
TI  - Lack of correlation between blood fibrinolysis and the immediate or post
      operative blood loss in transurethral resection of the prostate.
AB  - OBJECTIVE: To evaluate whether the activation of the extrinsic tissue-type
      plasminogen activator-related fibrinolysis is implicated in the blood loss in
      patients with benign prostatic hyperplasia, undergoing transurethral prostatic
      resection (TURP). PATIENTS AND METHODS: TURP was performed in 24 men and the
      operative and post-operative blood loss determined. The activation of the tissue
      type plasminogen activator-related fibrinolysis was followed using new sensitive
      and specific assays, and the changes related to the blood loss. Measurements of
      the plasma concentrations of free tissue-type plasminogen activator (t-PA)
      activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator
      inhibitor (PAI) activity, plasminogen activator inhibitor 1 (PAI-1) antigen,
      plasminogen (Plg) activity, plasminogen (Plg) antigen, alpha 2-antiplasmin (alpha
      2-AP), D-dimer and fibrin degradation products (FbDP) were all determined and the
      area under the curve (AUC) for each of these quantities correlated with the blood
      loss. RESULTS: TURP was followed by a marked activation of the fibrinolytic
      system. There was an immediate increase in systemic t-PA activity and t-PA
      antigen, coinciding with a significant drop in PAI activity. Post-operatively,
      PAI activity and PAI-1 antigen increased. The formation of plasmin was indicated
      by a fall in the plasma concentration of Plg activity and Plg-antigen and alpha 2
      AP but which increased significantly at the end of the study period. Increased
      systemic fibrinolytic activity was further confirmed by a marked increase in
      fibrin D-dimer and FbDP. There was no correlation between the AUC in the
      operative period of any of the fibrinolytic variables and the measured blood
      loss. In the post-operative period, t-PA antigen (P = 0.004), PAI activity (P =
      0.043), PAI-1 antigen (P = 0.016) and alpha 2-AP (P = 0.047) all correlated with
      the post-operative blood loss, while there was no correlation between fibrin D
      dimer or FbDP and blood loss. CONCLUSION: The fibrinolytic system is activated
      during and after TURP, but the increased activity is not of pathophysiological
      importance for the blood loss.

PMID- 9240190
TI  - A prospective randomized trial of interstitial radiofrequency therapy versus
      transurethral resection for the treatment of benign prostatic hyperplasia.
AB  - OBJECTIVE: To carry out a prospective randomized trial comparing interstitial
      radiofrequency therapy (IRFT) with transurethral resection of the prostate (TURP)
      in the treatment of bladder outlet obstruction (BOO) caused by benign prostatic
      hyperplasia. PATIENTS AND METHODS: The change in detrusor pressure at maximum
      flow (PdetQmax) was chosen as the primary measure of outcome but the symptom
      score, Qmax and residual volume were also measured. Patients with urodynamic
      evidence of BOO were randomized to receive IRFT (n = 25) or TURP (n = 25); the
      urodynamics were repeated 6 months after treatment. RESULTS: There was a
      statistically significant reduction in PdetQmax at 6 months for TURP (P < 0.001)
      and IRFT (P < 0.01) although the change seen in the latter group was probably not
      clinically relevant. Nevertheless, a clinically relevant reduction in symptom
      score occurred in both groups. Both techniques were associated with a low
      morbidity. CONCLUSION: IRFT is a cheap and safe technique which may be useful in
      the treatment of lower urinary tract symptoms in certain groups of patients in
      whom symptomatic improvement is a priority rather than objective outcome. The
      underlying mechanism for this symptomatic improvement is at present unclear.

PMID- 9240191
TI  - Morphological changes in prostatic adenomas after transurethral microwave
      thermotherapy.
AB  - OBJECTIVE: To study the extension and type of tissue damage in prostatic adenomas
      after transurethral microwave thermotherapy (TUMT). PATIENTS AND METHODS: Seven
      patients with benign prostatic hyperplasia and scheduled for open adenectomy
      underwent TUMT before surgery. TUMT was performed 2 h before operation in one
      patient, 24 h before in five and one week before in the remaining patient. The
      excised adenomas were examined by routine light microscopy. In addition, the
      terminal deoxynucleotidyl nick-end labelling (TUNEL) technique was used to search
      for DNA-strand breaks in areas with morphological alterations suggestive of
      apoptosis. Due to technical problems, TUMT was inadequate for one patient, i.e.
      the effect given was extremely low. RESULTS: In six cases, histopathological
      changes were found in limited areas extending from the urethra for 20-25 mm into
      the prostatic tissue. The predominant histopathological findings were areas of
      necrosis surrounded by cells with apoptotic features. The latter proved to be
      TUNEL-positive, i.e. they contained nuclei with DNA fragmentation of the
      apoptotic type. In the case with inadequate TUMT, there was no heat-induced
      tissue damage. CONCLUSION: The area of tissue damage seen after TUMT was
      relatively small compared with the volume of the prostates. The main
      histopathological finding was massive necrosis, but cells undergoing apoptosis
      were also identified. Obviously, temperatures lower than those leading to
      necrosis induced apoptosis, which is a discrete type of cell death not associated
      with oedema or inflammatory reaction.

PMID- 9240192
TI  - Transurethral needle ablation of the prostate for the treatment of benign
      prostatic hyperplasia: a collaborative multicentre study.
AB  - OBJECTIVE: To assess the efficacy and safety of transurethral needle ablation of
      the prostate (TUNA) for patients with symptomatic benign prostatic hyperplasia
      (BPH) in a multicentre trial. PATIENTS AND METHODS: Seventy-six patients were
      recruited from five centres; all were treated with the TUNA system consisting of
      a powered radiofrequency generator and a TUNA catheter. The patients were
      evaluated prospectively using the international prostate symptom score (IPSS),
      uroflowmetry, quality-of-life score, and other variables, and followed for a mean
      of 12 months after treatment. RESULTS: Sixty-eight patients were available for
      follow-up: TUNA produced significant improvements in the IPSS (median 22 before,
      to 7.5 after treatment). urinary flow rate (mean 8.7 before, to 11.6 mL/s after
      treatment) and quality-of-life score (median 5 before, to 2 after treatment) at
      12 months. CONCLUSIONS: If these early promising results are maintained. In the
      medium to long term, TUNA therapy will be a useful low-morbidity alternative for
      patients with symptomatic BPH.

PMID- 9240193
TI  - Significantly increased complication risks with mass circumcisions.
AB  - OBJECTIVES: To present the most serious complications from circumcision and to
      compare the complications caused during mass and single circumcisions performed
      by medically trained or untrained operators. PATIENTS AND METHODS: The study
      comprised both a retrospective and prospective analysis of 220 cases of
      complications from circumcisions occurring during the last decade and a
      comparison of the frequency and distribution of complications in mass (n = 700)
      and single (n = 600) circumcisions. RESULTS: Traditional (medically untrained)
      circumcisers were responsible for 85% of the complications and almost all the
      disastrous ones. The frequency of complications from mass circumcision was
      statistically significantly higher than that from circumcisions performed singly
      in operating room conditions (relative ratio 3.05 and P < 0.001). CONCLUSION:
      Circumcision can have serious life-threatening and prolonged complications. It
      should only be performed in medical institutions by suitably trained surgeons.
      Mass circumcisions organized for any purpose carry significantly greater risk and
      should be prevented.

PMID- 9240194
TI  - Decreased bcl-2 expression in segmental renal dysplasia suggests a role in its
      morphogenesis.
AB  - OBJECTIVE: To evaluate the potential role of bcl-2 and apoptosis in the
      histogenesis of segmental renal dysplasia. MATERIALS AND METHODS: Surgically
      resected specimens of dysplastic upper poles of duplex kidneys were studied from
      19 patients (mean age 3.4 years, range 2 months-9 years). Bcl-2 expression was
      detected immunohistochemically and apoptosis was investigated using the in situ
      end-labelling technique (ISEL). RESULTS: In the histologically normal areas of
      the specimens, bcl-2 expression was Intense in the proximal and distal convoluted
      tubules, moderate in Henle's loops and weak or absent in Bowman's capsule. In
      contrast, in the dysplastic areas there was no or markedly reduced expression of
      bcl-2 in mesenchyme and tubules. In the normal areas, apoptotic cells were
      extremely rare (0-1 per 25 high-power fields, HPFs), whereas in the dysplastic
      areas, some apoptotic cells were identified both in tubules (1-2 per 25 HPF) and
      in mesenchyme (5-8 per 25 HPF). CONCLUSIONS: As bcl-2 expression is required for
      normal kidney morphogenesis, finding no or markedly decreased expression of bcl-2
      in the dysplastic areas may be related to the persistence of dysplastic fetal
      type structures. Finding apoptosis adds further support to the concept that
      dysplasia represents arrested development at an early stage of morphogenesis
      before the period when bcl-2 assumes major importance.

PMID- 9240195
TI  - Pedicled penile skin for hypospadias 'rescue'.

PMID- 9240196
TI  - Modified reinforcement for vesico-urethral anastomosis after radical
      prostatectomy.

PMID- 9240197
TI  - Recurrent bladder exstrophy following cystolithotomy.

PMID- 9240198
TI  - Haematuria 2 years after transurethral resection of the prostate.

PMID- 9240199
TI  - Nephrogenic adenoma arising in an urethral diverticulum.

PMID- 9240200
TI  - Urinary bladder cancer in a girl with a slow-acetylator genotype and treated with
      sulphasalazine.

PMID- 9240202
TI  - Acutely inverted bladder through a vesicovaginal fistula: a complication of
      prolonged labour.

PMID- 9240203
TI  - Sarcoidosis of the penis.

PMID- 9240204
TI  - Transperitoneal ureter following ureteric reimplantation: a rare cause of small
      bowel obstruction and infarction.

PMID- 9240205
TI  - Giant stone in a partially herniated hour-glass bladder presenting as
      incarcerated incisional hernia.

PMID- 9240206
TI  - Squamous cell carcinoma arising in a para-urethral cyst.

PMID- 9240207
TI  - Management of ureteric calculi during pregnancy by ureteroscopy and laser
      lithotripsy.

PMID- 9240208
TI  - Segmental testicular ischaemia mimicking testicular tumor.

PMID- 9240209
TI  - The intrinsic intramural striated sphincter of the membranous urethra.

PMID- 9240210
TI  - Radical prostatectomy from three centres in the UK.

PMID- 9240211
TI  - Structural alterations in the tunica albuginea of the penis.

PMID- 9240212
TI  - The after-contraction in paediatric urodynamics.

PMID- 9240213
TI  - The after-contraction in paediatric urodynamics.

PMID- 9240214
TI  - The Internet for British Urologists.

PMID- 9240215
TI  - Methods for bursting Foley catheter balloons.

PMID- 9240216
TI  - Urinary tract obstruction during pregnancy: recent developments in imaging.

PMID- 9240217
TI  - Renal calculi in pregnancy.

PMID- 9240218
TI  - Urinary tract infection in pregnancy.

PMID- 9240219
TI  - Lower urinary tract symptoms in pregnancy.
AB  - Lower urinary tract symptoms are almost universal in the antenatal period and in
      most cases are transient. Retention of urine is one of the few conditions which
      must be treated as there may be long-term consequences. The symptoms of frequency
      and stress incontinence are those which have been most examined in pregnancy. It
      would appear that the former have no long-term sequelae but the latter may be an
      indicator of potential sphincter damage during delivery. The recent documentation
      of detrusor instability antenatally further confuses the picture and demonstrates
      the need for functional studies to determine the exact significance of these
      lower urinary tract symptoms.

PMID- 9240220
TI  - Management of urological tumours in pregnancy.
AB  - Urological tumours are rare in pregnancy and may be mistaken for other, more
      common conditions such as urinary infection, pyelitis, threatened abortion or pre
      eclampsia. With modern imaging techniques, especially ultrasonography and NMR,
      the diagnosis can be accurately established. In collaboration with obstetric and
      medical colleagues, the urologist can deal with these tumours safely and
      effectively, provided that the timing and extent of treatment are carefully
      tailored to the stage of the pregnancy.

PMID- 9240221
TI  - Pregnancy and renal transplantation.

PMID- 9240222
TI  - How to avoid litigation: the urologist's view.

PMID- 9240223
TI  - Debate: 'post-operative urinary fistulae should be managed by gynaecologists in
      specialist centres'.

PMID- 9240224
TI  - Lower urinary tract symptoms in women: who to investigate and how.

PMID- 9240225
TI  - Ambulatory bladder monitoring: is it an advance?

PMID- 9240226
TI  - Developments in our understanding of detrusor instability.
AB  - It is important to recognize that our understanding of detrusor instability is
      far from complete. Although the significance of some of the abnormalities
      reported is unclear, it is likely that several factors will eventually be found
      to contribute to the overall clinical picture. Nevertheless, there is increasing
      evidence that the development of post-junctional supersensitivity of the detrusor
      muscle is implicated in each of the clinical subgroups of instability. Partial
      denervation of the detrusor appears to be the mechanism responsible for this in
      obstructive detrusor instability, but other abnormalities causing a chronic
      decrease in the excitatory motor innervation to the detrusor (e.g.
      decentralization, pre-synaptic inhibition) could produce similar effects and may
      therefore be involved. This evidence of a specific abnormality at the cellular
      level offers scope for therapy for detrusor instability with a new range of
      drugs, using agents that hyperpolarize the detrusor muscle membrane or modify
      calcium activation. However, bladder specificity remains a fundamental problem in
      the development of effective therapeutic agents for detrusor instability and
      poses the great challenge for the future.

PMID- 9240227
TI  - The assessment and surgical management of recurrent pelvic cancer of the female
      genitalia.

PMID- 9240228
TI  - Pelvic surgery after radiotherapy.

PMID- 9240229
TI  - Female adult reconstructive urology.

PMID- 9240230
TI  - Total pelvic reconstruction after exenteration for recurrent cervical cancer.

PMID- 9240231
TI  - Rehabilitation and nursing aspects of urological reconstructive surgery.

PMID- 9240232
TI  - What is the right operation for stress incontinence? A gynaecological view.

PMID- 9240233
TI  - What is the right operation for stress incontinence? A urologist's view.

PMID- 9240234
TI  - Magnetoencephalography/magnetic source imaging in the assessment of patients with
      epilepsy.
AB  - Magnetoencephalographic (MEG) dipole source localization is a particularly
      promising new tool for noninvasive presurgical evaluation of epileptogenic foci.
      It is potentially more accurate than EEG localization techniques because magnetic
      fields are not attenuated or distorted by the skull and scalp, which allows
      cerebral sources to be modeled more simply. MEC spike and seizure sources are
      routinely co-registered with the patient's brain MRI for clinical interpretation.
      This has been called magnetic source imaging. Numerous studies have shown that
      MEG localization of foci agreed with lesion position, depth electrode and ECoG
      data, PET and MRI findings, and surgical success. The recent development of whole
      head sensor arrays has greatly enhanced the case with which epileptiform magnetic
      fields can be recorded and analyzed.

PMID- 9240235
TI  - Clinical challenges in invasive monitoring in epilepsy surgery.
AB  - Invasive monitoring aids in selecting patients for epilepsy surgery. This article
      reviews the methods employed to obtain intracranial EEG, data interpretation, and
      problems that arise during intracranial investigations. The relative merits of
      depth, subdural, epidural, and foramen ovale electrodes are reviewed, and a
      strategy for their use is suggested. Characteristic interictal and ictal EEG
      findings are summarized, and the problems encountered in interpreting data are
      discussed.

PMID- 9240236
TI  - Clinical applications of magnetic resonance spectroscopy.
AB  - Magnetic resonance spectroscopy (MRS) is a new tool for evaluation of patients
      with epilepsy, demonstrating abnormalities of energy and lipid metabolism ictally
      and, more recently, interictally. These metabolic abnormalities include increased
      inorganic phosphate, pH, and decreased phosphomonoesters as determined by 31P
      MRS, as well as decreased N-acetylaspartate determined by 1H MRS. Furthermore,
      increased lactic acid has been detected postictally. These metabolic changes
      appear to be confined to the region of seizure origination and can be detected
      interictally. Therefore, they can be used for lateralization of the epileptogenic
      focus. Ongoing research suggests that these abnormalities may also be useful in
      localization of the focus, demonstrating metabolic alterations in temporal lobe
      epilepsy (TLE) similar to those in neocortical epilepsy. However, further
      technical development will be required before the goal of using these techniques
      for localization of the epileptogenic focus can be realized. For TLE lobe
      epilepsy at least, the clinical utility of 1H MRS to lateralize the seizure focus
      has clearly been demonstrated by several centers. The consistent findings in TLE
      suggest that 1H MRS is ready to become part of the evaluation process of patients
      with medically refractory epilepsy being evaluated for seizure surgery.

PMID- 9240237
TI  - Neuropsychological evaluation in epilepsy surgery.
AB  - Neuropsychology has played a prominent role throughout the modern era of epilepsy
      surgery. Neuropsychology, including the Wada test, has been of benefit in
      documenting dysfunction associated with a lateralized temporal lobe seizure
      onset. In addition, neuropsychological results have some predicative power
      regarding seizure outcome following anterior temporal lobectomy. The current
      status of neuropsychology in patient evaluation and outcome prediction will be
      presented. Differences between the Wada test, an inactivation procedure, and
      functional magnetic resonance imaging, which is an activation procedure, will be
      discussed. This paper will also present preliminary information about the
      Wechsler Adult Intelligence Scale-III, the recent revision of the most commonly
      used test of intellectual function, and its effects on neuropsychological
      performance results.

PMID- 9240238
TI  - Comprehensive management of epilepsy in persons with mental retardation.
AB  - Epilepsy is a common occurrence in persons with mental retardation. The
      application of recent advances in epilepsy research to patients with mental
      retardation has shown that well-accepted principles of management are as relevant
      for multiply handicapped people as for those with epilepsy alone. Quality
      enhancement is emphasized as the overarching concept that determines the quality
      of care provided to patients with epilepsy and mental retardation. This article
      reviews the comprehensive management of epilepsy, discusses what is known at
      present, and indicates what is not known and needs further research.

PMID- 9240239
TI  - Maximizing the health of women with epilepsy: science and ethics in new drug
      development.
AB  - Issues of unique concern to women with epilepsy largely arise from gender-based
      physiological differences. Female sex steroid hormones may alter the expression
      of epilepsy and the efficacy of antiepileptic drugs (AEDs). Seizures and AEDs in
      turn affect the hypothalamic-pituitary axis and can adversely impact reproductive
      function and bone health. Maternal seizures and exposure to AEDs may compromise
      fetal development. At this time, women with epilepsy and their medical caretakers
      do not have access to all the information necessary to formulate a treatment plan
      that will have the least impact on reproductive and general health. In part, this
      is because reproductive aged women are excluded from the earliest phases of drug
      testing and pregnant and lactating women are excluded from all aspects of new
      drug development. Therefore, as new AEDs enter the marketplace, women with
      epilepsy must decide whether a new AED is appropriate for therapy based on very
      limited information. Postmarketing surveillance of gender-specific adverse
      effects, as with all adverse effects, depends on voluntary reporting. Only a
      small percentage of significant adverse events are believed to be captured by the
      present system. Consumers, ethicists, and some physician groups are now arguing
      that women should be included in all aspects of the development of drugs they
      will ultimately use-even pregnant and lactating women. Some of the issues of
      concern for women with epilepsy regarding epilepsy treatment, reproductive
      function and general health will be reviewed, followed by a discussion of the
      drug development process and how it does, and could better, address the concerns
      of women.

PMID- 9240241
TI  - Some lessons learned in the care of the elderly.
AB  - This article is designed to acquaint physicians not trained in geriatrics with
      some precepts concerning the care of the elderly. It presents a summary of the
      experience in the care of over 2,000 outpatients over the age of 65 who were seen
      at a community hospital geriatric evaluation unit and resource center. The
      findings reaffirmed the importance of concentrating on the preservation and
      restoration of function in the care of the frail elderly. Although there are no
      clinical skills unique to geriatrics, but the approach to the gathering of
      clinical data in people with multiple and overlapping problems and disabilities
      must be structured differently. There is less emphasis on precise diagnosis, much
      less emphasis on the concept of cure, and more emphasis on structuring a
      medical/social response to the dominant problem or problems.

PMID- 9240240
TI  - Don't test, do sell: legal implications of inclusion and exclusion of women in
      clinical drug trials.
AB  - This article explores the historic underpinnings of the exclusion of women from
      clinical drug trials, identifies recent developments, and examines legal
      implications for women with epilepsy and for others. Distinguishing stakeholders
      and their interests may lead to policies that better serve all. Past and present
      statutory, regulatory, and judicial frameworks were reviewed, as well as legal,
      medical, and historical commentary. Traditionally, researchers and manufacturers
      have not tested particular drugs on women. Physicians and pharmacists routinely
      prescribe and sell these same medications regardless of gender. Only since 1993
      have females been more likely to be included in clinical drug trial subject
      pools. The impact of past and future practices on health care provision and legal
      liability remains unknown. A policy of "Don't test, do sell" will not protect
      women with epilepsy or would-be defendants. At this time the most effective
      shields will involve procurement of informed consent as well as testing of both
      women and men. In the long run, tort, health care, and regulatory reform will
      best serve all interested persons. Inclusion of women in clinical drug trials has
      become a how question, not an if one.

PMID- 9240242
TI  - Seizures in medically complex patients.
AB  - Seizures are not an uncommon complication of medical conditions and should not be
      ascribed simply to "multifactorial" causes. Although many interacting factors may
      contribute to a lowered threshold for seizures, a careful systems-oriented search
      usually yields specific factors that are of primary importance. Not all medically
      complex patients with seizures have persistent or irreversible processes that
      lead to recurrent seizures or a need for maintenance antiepileptic drugs (AEDs).
      Because AEDs contribute to the potential for drug interactions, side effects, and
      toxicities in situations already encumbered with significant polypharmacy, the
      decision not to initiate such therapy can be even more important than selecting
      the best agent, best route of administration, and best dose from a growing list
      of AEDs.

PMID- 9240243
TI  - Do men become infertile after having sexually transmitted urethritis? An
      epidemiologic examination.
AB  - OBJECTIVE: To critically assess the possibility that gonorrhea or chlamydia
      causes male infertility. DESIGN: Comprehensive literature review structured to
      evaluate the epidemiologic tenets for causality, including biologic plausibility,
      strength of association, dose response, consistency, temporality, and treatment
      effect. RESULT(S): It is biologically plausible that gonorrhea and/or chlamydia
      could cause male infertility. There is clinical and pathologic evidence linking
      these pathogens to urethritis, linking urethritis to epididymo-orchitis, and
      linking epididymo-orchitis to infertility. Retrospective epidemiologic results
      also support an association between chlamydia serologies and male infertility,
      which in most of these small studies does not reach the level of statistical
      significance. However, there is no consistent epidemiologic evidence that these
      pathogens alter sperm characteristics. We discuss the methodologic limitations of
      previous epidemiologic studies and suggest strategies for future research.
      CONCLUSION(S): Whether gonorrhea and/or chlamydia cause male infertility is
      currently unclear. Sound methodologic research strategies must be applied to
      future studies.

PMID- 9240244
TI  - Sperm or spermatid conception?

PMID- 9240245
TI  - Cumulative pregnancy analysis of one-tube versus two-tube tubal anastomosis.
AB  - OBJECTIVE: To determine the prognosis for pregnancy when tubal anastomosis can be
      performed on only one tube. DESIGN: Prospective collection of demographic and
      clinical data. SETTING: University medical center. PATIENT(S): One hundred twenty
      six women undergoing elective sterilization reversal. INTERVENTION(S):
      Sterilization reversal was performed by five reproductive endocrine surgeons. In
      35 cases, only one tube could be treated surgically. In all cases, this was
      because of a previous salpingectomy or inadequate distal tubal segment. MAIN
      OUTCOME MEASURE(S): Cumulative probability of pregnancy in the two groups (one
      tube or two tubes) was analyzed by survival analysis and logistic regression.
      Survival curves were compared by log-rank testing. RESULT(S): Comparison of
      survival curves revealed no difference between the logistic regression curves for
      probability of conception after anastomosis of one tube versus two tubes.
      Logistic regression revealed a similar cumulative probability of conception with
      a two-tube (0.76) and a one-tube anastomosis (0.63). The monthly fecundity rates
      were 0.032 and 0.034 for a two-tube and one-tube anastomosis, respectively. There
      were no differences between the groups with respect to age, gravidity, or parity.
      Virtually all pregnancies occurred within 2 years of surgery. CONCLUSION(S): The
      prognosis for conception after one-tube anastomosis was the same as for two-tube
      anastomosis.

PMID- 9240246
TI  - Fertility after organ-preserving surgery of ectopic pregnancy: results of a
      multicenter study.
AB  - OBJECTIVE: To evaluate the postoperative fertility rate after ectopic pregnancy
      (EP) and to compare the impact of different surgical techniques. DESIGN:
      Prospective, multicenter trial. SETTING: Twenty-five centers with microsurgical
      facilities. PATIENT(S): A total of 1,025 patients with EP were enrolled between
      1984 and 1990. INTERVENTION(S): Organ-preserving operation and at least one
      patent remaining tube. Evaluation of postoperative outcome by standardized
      questionnaires. MAIN OUTCOME MEASURE(S): Postoperative fertility in terms of
      pregnancy rate (PR) and recurrent ectopic implantation. RESULT(S): The PR was
      similar after wedge resection (45.9%) and salpingotomy or milk out (42.0%). The
      recurrence rates did not differ between both groups (7.5% versus 8.2%). In
      patients with a blocked or absent contralateral tube, the PR was poor (31.2%),
      and the recurrence rate of EP was high (16.0%), indicating that most pregnancies
      are achieved through the contralateral tube. CONCLUSION(S): The postoperative
      fertility rate after an EP is reduced. The type of surgery usually has no
      significant impact. In the case of a blocked or absent contralateral tube, the
      patient must be informed about the significantly reduced fertility rate and the
      elevated risk for EP recurrence.

PMID- 9240247
TI  - Unicornuate uterus and rudimentary horn.
AB  - OBJECTIVE: To evaluate clinical implications of the unicornuate uterus and
      rudimentary horn. DESIGN: A retrospective study. SETTING: A university hospital.
      PATIENT(S): Forty-two women who had a unicornuate uterus with or without
      rudimentary horn. INTERVENTION(S): The rudimentary horn was removed in 21 cases.
      MAIN OUTCOME MEASURE(S): Presence of other anomalies, fertility, and outcome of
      pregnancies were studied. RESULT(S): A right unicornuate uterus with
      noncommunicating rudimentary horn was the most common type of uterine anomaly.
      Unilateral renal agenesis was found in 13 (38%) of 34 cases. Six (14%) of the 42
      patients had primary infertility. Thirty-four women produced 93 pregnancies;
      ectopic pregnancy (EP; rudimentary horn, tubal) occurred in 20 of these cases
      (22%). The pregnant uterine horn ruptured in 3 of 7 cases. Eight (57%) of the 14
      women with infertility underwent treatment by IVF-ET; 4 of them conceived, and 2
      had term delivery. The fetal survival rate was 61%, prematurity 17%, fetal growth
      retardation 5%, and the spontaneous intrauterine (IU) abortion rate was 16%.
      Pregnancy-induced hypertension (PIH) was more common in women lacking a kidney
      than in those with two kidneys. CONCLUSION(S): The high number of EPs indicates
      removal of rudimentary horn and its tube when diagnosed. The prognosis of IU
      pregnancy is not impaired in the unicornuate uterus although prematurity
      threatens. Unilateral renal agenesis is associated with PIH.

PMID- 9240248
TI  - Changes in atherogenic lipids and lipoproteins during natural and hyperstimulated
      cycles in healthy women.
AB  - OBJECTIVE: To compare changes in the concentrations of Lp(a) lipoprotein and
      other atherogenic lipids and lipoproteins in natural and hyperstimulated ovarian
      cycles. DESIGN: Open, prospective study. SETTING: Academic department in a
      teaching hospital. PATIENT(S): Normal ovulatory women served as controls and the
      treatment group consisted of women undergoing ovarian hyperstimulation.
      INTERVENTION(S): The treatment group received hMG on a fixed regimen. MAIN
      OUTCOME MEASURE(S): Measurements of serum lipids and lipoproteins were made in
      both natural and hyperstimulated cycles. RESULT(S): There was a significant
      increase in the median concentration of Lp(a) lipoprotein from 10.1 to 10.7 mg/dL
      in the luteal compared with the proliferative phase of unstimulated cycles. In
      hyperstimulated cycles, there was a significant increase in the median
      concentration of Lp(a) lipoprotein from 9.7 mg/dL in the proliferative phase to
      11.3 mg/dL in the luteal phase. Reductions in concentrations of total cholesterol
      and low-density lipoprotein cholesterol were found in the luteal phase of
      hyperstimulated cycles. CONCLUSION: Concentrations of Lp(a) lipoprotein increase
      during the luteal phase of both natural and hyperstimulated ovarian cycles.

PMID- 9240249
TI  - Different dysregulations in adrenal steroid biosynthesis as a prevalent cause of
      hyperandrogenism in women from southern Italy.
AB  - OBJECTIVE: To investigate the presence of a dysregulation in steroid biosynthesis
      in women from southern Italy. DESIGN: Controlled clinical study. SETTING: Normal
      and hyperandrogenic women referred to the Endocrinology Unit of Federico II
      University Medical School of Naples. PATIENT(S): One hundred fifty untreated
      young hyperandrogenic women and 50 normal age-matched women. INTERVENTION(S):
      Morning (basal) blood samples obtained in the early follicular phase and after a
      long (360 minute) ACTH stimulation test. MAIN OUTCOME MEASURE(S): The adrenal
      maximal response was calculated as stimulus under curve areas (AUCa), and all
      steroids were assayed using RIA methods. RESULT(S): A dysregulation of 21
      hydroxylase was found in 22 patients (14.7%), with a prevalent increase of 17
      alpha-hydroxyprogesterone AUC, whereas in 9 hirsute women (6%), there was a
      prevalent significant increase in 11-deoxycortisol AUC. In 5 women (3.3%), DHEA
      and DHEAS basal and AUCs plasma levels were increased, suggesting an impaired 3
      beta-olo-dehydrogenase activity. The remaining 114 hyperandrogenic women (76%)
      compose the nonadrenal group, with a probable diagnosis of primitive functional
      ovarian hyperandrogenism. CONCLUSION(S): Considering the high prevalence of
      hirsutism and oligomenorrhea in our female hyperandrogenic population, we suggest
      an adrenal hyperresponsiveness likely due to a dysregulation in enzymes related
      to androgen adrenal steroidogenesis.

PMID- 9240250
TI  - Sonographic assessment of endometrial pattern and thickness in patients treated
      with clomiphene citrate, human menopausal gonadotropins, and intrauterine
      insemination.
AB  - OBJECTIVE: To analyze the endometrium sonographically in patients undergoing
      controlled ovarian stimulation with clomiphene citrate (CC) in addition to
      menotropins to determine the significance of endometrial pattern and thickness on
      pregnancy rate (PR). DESIGN: A prospective study analyzing patients receiving
      sequential CC and hMG followed by hCG and IUI. Patients who exhibited homogeneous
      endometrial patterns were compared with those who had trilaminar patterns
      visualized by transvaginal sonography at the end of the follicular phase.
      Endometrial thickness was emphasized in this group of patients. SETTING: Tertiary
      infertility center. PATIENT(S): All patients receiving sequential CC and hMG
      therapy at a tertiary infertility center. INTERVENTION(S): All patients received
      individualized dosing of hMG after 5 days of CC. Transvaginal sonography was
      performed 15 hours before hCG administration. Intrauterine insemination was
      performed 36 hours after hCG injection. MAIN OUTCOME MEASURE(S): Occurrence of
      pregnancy as determined by serially rising beta-hCG titers and sonographic
      confirmation. RESULT(S): During the study period, 223 patients were analyzed.
      Fifty patients had a homogeneous endometrium, whereas 173 patients had a
      trilaminar pattern. In the homogeneous group, the PR was 8%, and in the
      trilaminar group it was 21%. There was no significant difference in age, parity,
      diagnosis, peak E2 level, and mature follicle number between the two groups.
      Although homogeneous patterns were associated with thinner endometrium, no
      difference in PRs could be discerned within the trilaminar group on the basis of
      endometrial thickness. CONCLUSION(S): In patients receiving sequential CC and hMG
      ovarian stimulation, a homogeneous endometrial pattern on the day of hCG
      administration predicts a significantly decreased PR compared with a trilaminar
      pattern.

PMID- 9240251
TI  - Expression of interstitial collagenase (matrix metalloproteinase-1) is related to
      the activity of human endometriotic lesions.
AB  - OBJECTIVE: To determine whether interstitial collagenase (matrix
      metalloproteinase-1), known to play a pivotal role in the initiation of
      menstruation, contributes to the pathogenesis of endometriosis. DESIGN: Serial
      sections of peritoneal red and black endometriotic lesions, ovarian endometriotic
      cysts, and rectovaginal adenomyotic nodules were analyzed by in situ
      hybridization for the expression of matrix metalloproteinase-1 by silver staining
      for the integrity of the fibrillar extracellular matrix and by immunolabeling for
      the abundance of sex steroid receptors. SETTING: Academic hospital and research
      laboratory. PATIENT(S): Premenopausal women undergoing laparoscopy for
      endometriosis. INTERVENTION(S): Biopsy of endometriotic lesions, combined with
      endometrium whenever possible. MAIN OUTCOME MEASURE(S): Expression of matrix
      metalloproteinase-1 messenger RNA (mRNA). RESULT(S): Matrix metalloproteinase-1
      mRNA was expressed focally in red peritoneal and ovarian endometriosis
      irrespective of the phase of the menstrual cycle but was not detectable in black
      peritoneal and rectovaginal lesions. Foci of matrix metalloproteinase-1
      expression closely correlated with matrix breakdown and with the absence of P
      receptors in adjacent epithelial cells. CONCLUSION(S): Correlation of matrix
      metalloproteinase-1 expression with activity of endometriotic tissue suggests its
      involvement in tissue remodeling and bleeding, and possibly in the secondary
      shedding and reimplantation of endometriotic lesions.

PMID- 9240252
TI  - Insulin-like growth factors and insulin-like growth factor binding proteins in
      androgen-dominant ovarian follicles from testosterone-treated female-to-male
      trans-sexuals.
AB  - OBJECTIVE: To determine insulin-like growth factor (IGF)-I and IGF-II levels, IGF
      binding protein (IGFBP) profile, and IGFBP-4 protease activity in androgen
      dominant follicular fluid (FF) from female-to-male trans-sexuals and to compare
      with those in follicles from normocycling women. DESIGN: Follicular fluid samples
      were obtained from four female-to-male trans-sexuals and 15 women with normo
      ovulatory cycles at the Dijkzigt Academic Hospital. Western ligand blot analysis
      and protease assays were used to determine IGFBP profile, and immunoradiometric
      assays were used to detect IGF levels. SETTING: The study was performed in two
      academic medical centers. PATIENT(S): Female-to-male trans-sexuals and women with
      normo-ovulatory cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S):
      Determination of IGF levels and IGFBP profile. RESULT(S): Insulin-like growth
      factor I levels in FF from female-to-male trans-sexuals were not significantly
      different compared with levels in androgen-dominant FF and estrogen-dominant FF.
      Significantly lower levels of IGF-II were observed in FF from female-to-male
      trans-sexuals than in estrogen-dominant FF, whereas IGF-II levels in FF from
      female-to-male trans-sexuals were not significantly different than those in
      androgen-dominant FF. Similar IGFBP profiles from FF from female-to-male trans
      sexuals and androgen-dominant FF were noted, with markedly elevated levels of the
      31- and 24-kd IGFBPs and a 28-kd IGFBP, compared with estrogen-dominant FF. An
      IGFBP-4-specific metalloserine protease that is active in estrogen-dominant FF
      likewise was undetected in FF from female-to-male trans-sexuals. CONCLUSION(S):
      Follicles developing under the influence of exogenous androgens in ovaries in
      female-to-male trans-sexuals appear to be similar to androgen-dominant follicles
      in normo-ovulatory women with regard to IGF-I and IGF-II levels, IGFBP profile,
      and the absence of IGFBP-4 protease activity.

PMID- 9240253
TI  - Colony stimulating factor-1 in human follicular fluid.
AB  - OBJECTIVE: To evaluate colony stimulating factor-1 (CSF-1) concentrations in
      serum and follicular fluid (FF) at the time of oocyte retrieval and to test for
      presence of messenger RNA (mRNA) for CSF-1 and its receptor, c-fms, in FF cells.
      DESIGN: Collection of serum and FF at the time of oocyte retrieval. SETTING: A
      university IVF program. PATIENT(S): Forty-five women undergoing oocyte retrieval
      for IVF. INTERVENTION(S): Serum and FF were obtained from 24 women, and FF only
      was obtained from 21 women. MAIN OUTCOME MEASURE(S): Colony-stimulating factor-1
      concentrations were determined by RIA, and the presence of mRNA for CSF-1 and c
      fms was determined by reverse transcriptase-polymerase chain reaction. RESULT(S):
      Mean FF concentrations of CSF-1 were significantly higher than mean serum levels
      (10.0 +/- 1.3 and 3.6 +/- 0.3 (+/-SE) ng/mL, respectively). Colony-stimulating
      factor-1 and c-fms message were detected in FF cells, and alternatively spliced
      forms of CSF-1 message were present. CONCLUSION(S): The presence of CSF-1, a
      primary regulator of tissue macrophages, in FF, and the presence of mRNA for CSF
      1 and its receptor c-fms in FF-derived cells, suggest a role for this growth
      factor in ovarian function.

PMID- 9240254
TI  - Age-related decline in fertility: a link to degenerative oocytes?
AB  - OBJECTIVE: To determine whether the age-related decline in fertility is due to
      degenerative oocytes or to aneuploidy. DESIGN: Retrospective. SETTING: Fertility
      center of a public and tertiary institution. PATIENT(S): One hundred fifty-one
      women (ages 24 to 44 years) undergoing 158 cycles of conventional IVF or IVF with
      intracytoplasmic sperm injection (ICSI) between January 1993 and December 1995
      were divided into three age groups (group 1, < or = 34 years; group 2, between 35
      and 39 years; and group 3, > or = 40 years). They were selected on the basis of
      available oocytes that remained unfertilized after IVF and that had analyzable
      chromosomes. INTERVENTION(S): Standard pituitary down-regulation and ovarian
      stimulation with FSH and hMG were done for both IVF and ICSI patients. In
      addition, all patients were given luteal phase support with P, administered
      orally, via pessaries, or by IM injections from the day of transfer. MAIN OUTCOME
      MEASURE(S): Fertilization rates and pregnancy rates (PRs), and cytogenetic
      analyses of unfertilized oocytes. RESULT(S): Although fertilization rates were
      not different among women in groups 1, 2, and 3 (50.9%, 49.3%, and 37.9%,
      respectively), PRs were significantly lower between groups 1 and 3 (43.2% versus
      14.3%). A total of 383 oocytes were examined, of which 287 (75%) could be
      karyotyped. Of these, 201 oocytes showed a normal 23,X karyotype (70%), 40
      (13.9%) were aneuploid, 24 (8.4%) were diploid, 12 (4.2%) had structural
      aberrations, and 13 (4.5%) had single chromatids only. No increase in the
      aneuploidy rate was detected between groups 1 and 2 (14.8% versus 12.4%).
      However, highly significant differences in the rate of oocyte chromosome
      degeneration, characterized by chromosomes splitting into unassociated
      chromatids, were observed with increasing age (group 1, 23.7%; group 2, 52.0%;
      and group 3, 95.8%). CONCLUSION(S): It seems that the age-related decline in
      fertility may be due more to degenerative oocytes than to aneuploidy. A decline
      in the number of oocytes retrieved with age may be of less importance than the
      decline in oocyte quality. Women in the older age group have a higher chance of
      achieving pregnancy from ovum-donation programs than by persisting in using their
      own aged oocytes, which have a very poor prognosis for success.

PMID- 9240255
TI  - Basal estradiol and follicle-stimulating hormone predict fecundity in women of
      advanced reproductive age undergoing ovulation induction therapy.
AB  - OBJECTIVE: To determine the prognostic value of single basal E2 and FSH levels as
      predictors of fecundity in women of advanced reproductive age who are undergoing
      ovulation induction with IUI therapy. DESIGN: Prospective, observational.
      SETTING: Fertility service of university medical center. PATIENT(S): Infertile
      couples in which the female partner was > or = 38 years old. INTERVENTION(S):
      Single assessment of basal E2 and FSH levels and ovulation induction with IUI.
      MAIN OUTCOME MEASURE(S): Cumulative and clinical pregnancy rates and live birth
      rates. RESULT(S): All live births occurred in patients with a basal E2 < or = 80
      pg/mL (conversion factor to SI unit, 3.671), a basal FSH < or = 13 mIU/mL
      (conversion factor to SI unit, 1.00), and a chronological age < or = 42 years. In
      women 38 to 42 years of age, 10.3% had elevated basal E2 (> 80 pg/mL) in
      combination with normal basal FSH (< or = 13 mIU/mL), and no live births occurred
      in these couples. The cumulative live birth rate after four treatment cycles in
      women 38 to 42 years of age with both normal basal E2 (< or = 80 pg/mL) and FSH
      levels (< or = 13 mIU/mL) was 43.9%. CONCLUSION(S): Basal E2 improves the ability
      to predict fertility potential compared with basal FSH and chronological age
      alone. Basal E2, in combination with basal FSH and chronological age, has useful
      prognostic value in prospectively counseling patients of advanced reproductive
      age who are considering ovulation induction and IUI therapy.

PMID- 9240256
TI  - Patient dropout in an assisted reproductive technology program: implications for
      pregnancy rates.
AB  - OBJECTIVE: To study patient dropout and its impact on crude and cumulative
      pregnancy rates (PRs) after assisted reproductive technology (ART). DESIGN:
      Retrospective cohort study. SETTING: University hospital-based tertiary care
      fertility clinic. PATIENT(S): Two hundred two couples applying for their first
      ART treatment cycle. MAIN OUTCOME MEASURE(S): Drop-out rate and PR per cycle,
      cumulative drop-out rate and cumulative PR. RESULT(S): After three treatment
      cycles, the cumulative drop-out rate was 126 of 202 (62.4%); 13.9% (n = 28) was
      due to active censoring. Active censoring was shown to flatter cumulative PRs by
      life-table analysis. CONCLUSION: Dropout from ART is high, even when ART costs
      are covered by health cost insurance. Life-table analysis overestimates
      cumulative PRs in ART.

PMID- 9240257
TI  - Preprogrammed, unmonitored ovarian stimulation reduces expense without
      compromising the outcome of assisted reproduction.
AB  - OBJECTIVE: To determine if a novel, preprogrammed, unmonitored stimulation
      protocol could reduce the cost of assisted reproductive technology (ART) without
      compromising outcome or safety. DESIGN: Prospective, nonrandomized study of
      unmonitored ART versus traditional monitoring. SETTING: University ART program.
      PATIENT(S): Infertile women aged < 39 years, with a basal FSH level < 15 mIU/mL
      (conversion factor to SI unit, 1.00) and regular menstrual cycles, undergoing
      ART. INTERVENTION(S): Oocyte retrieval was performed at a predetermined time in
      72 unmonitored cycles based on age and basal FSH level. No monitoring of any type
      was performed before retrieval. There were 86 monitored control cycles. MAIN
      OUTCOME MEASURE(S): The number of oocytes, and embryos; complications including
      ovarian hyperstimulation. RESULT(S): The total cost for unmonitored ART was
      significantly less than for monitored cycles. There was no difference between
      groups for patient age, number of oocytes obtained, or number of metaphase II
      oocytes. For non-male-factor patients, the number of oocytes fertilized, number
      of embryos transferred, and the clinical pregnancy rates were comparable. There
      was one case of severe hyperstimulation requiring hospitalization in the
      unmonitored group. CONCLUSION(S): This novel, unmonitored ovarian stimulation
      protocol provides ART at a significantly lower cost than is incurred with
      traditional monitoring, with no apparent compromise in outcome.

PMID- 9240258
TI  - Intravenous albumin does not prevent the development of severe ovarian
      hyperstimulation syndrome.
AB  - OBJECTIVE: To determine the efficacy of IV albumin in the prevention of severe
      ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective study group with
      historical control. SETTING: University hospital-based IVF program. PATIENT(S):
      Between 1993 and 1995, 42 consecutive patients undergoing IVF-ET or tubal ET who
      had serum E2 levels > or = 3,600 pg/mL (conversion factor to SI unit, 3.671) on
      the day of hCG administration and/or > or = 20 oocytes retrieved were considered
      at high risk for severe OHSS and were selected as the control group. From
      December 1995 to October 1996, IV albumin was given to 30 consecutive patients
      who fulfilled these criteria. INTERVENTION(S): The treatment group received IV
      albumin after oocyte retrieval. MAIN OUTCOME MEASURE: Occurrence of severe OHSS.
      RESULT(S): None of the 16 patients in the treatment group in nonconception cycles
      developed severe OHSS, compared with 5 (21.7%) of 23 in the control group. In
      conception cycles, 4 (28.6%) of 14 patients in the treatment group developed
      severe OHSS, compared with 9 (47.4%) of 19 in the control group. All 4 patients
      with multiple pregnancies in the treatment group developed severe OHSS, compared
      with 3 (60%) of 5 in the control group. None of the 10 patients with singleton
      pregnancies in the treatment group developed severe OHSS, compared with 6 (42.9%)
      of 14 in the control group. CONCLUSION(S): Intravenous albumin prevents severe
      OHSS in high-risk patients who did not conceive or who carried singleton
      pregnancies, but not in the patients with high-order pregnancies.

PMID- 9240259
TI  - In premature luteinization, progesterone induces secretory transformation of the
      endometrium without impairment of embryo viability.
AB  - OBJECTIVE: To determine the effect of serum P on endometrial histology in
      stimulated cycles. DESIGN: Prospective clinical study. SETTING: Community
      hospital-based donor oocyte program. PATIENT(S): Fertile young oocyte donors and
      infertile donor oocyte recipients. INTERVENTION(S): Oocyte donors underwent
      gonadotropin stimulation after midluteal pituitary suppression. Endometrial
      biopsies were obtained at the time of oocyte retrieval. MAIN OUTCOME MEASURE(S):
      Endometrial histology and serum P levels in oocyte donors. Pregnancy and
      implantation rates in oocyte recipients. RESULT(S): Thirteen biopsy specimens
      (52.0%) showed in-phase mixed proliferative pattern (days 14 to 15), whereas 12
      (48.0%) were secretory (days 16 to 17). On the day of hCG, subjects with
      secretory endometrium had higher P of 1.7 ng/mL (5.4 nmol/L) than women with the
      mixed pattern (0.8 ng/mL [2.5 nmol/L]). Progesterone > or = 0.9 ng/mL had a 78.6%
      positive predictive value for secretory transformation. In 75.0% of cycles with
      secretory endometrium, P was > or = 0.9 ng/mL, (2.9 nmol/L) as early as 2 days
      before hCG. Both mixed and secretory patterns were associated with similar
      clinical pregnancy rates (57.1% and 60.0%, respectively) and delivery rates
      (38.1% and 50.0%, respectively) in recipients. CONCLUSION(S): Subtle elevation of
      P induced secretory endometrial transformation without reduction in embryo
      viability.

PMID- 9240260
TI  - Midfollicular anticardiolipin and antiphosphatidylserine antibody titers do not
      correlate with in vitro fertilization outcome.
AB  - OBJECTIVE: To determine the prevalence of anticardiolipin and
      antiphophatidylserine antibodies in an IVF population and to correlate their
      presence and specific isotype with IVF cycle outcome. DESIGN: Retrospective
      clinical study using stored midfollicular sera for determination of antibody
      status. SETTING: University hospital infertility clinic. PATIENT(S): Women who
      underwent IVF treatment in 1991. INTERVENTION(S): Midfollicular sera were used to
      assess antibody status during the time of stimulation for IVF. MAIN OUTCOME
      MEASURE(S): Anticardiolipin and antiphosphatidylserine antibody titers and
      biochemical or sonographic documentation of IVF cycle outcome. RESULT(S): The
      overall prevalence of anticardiolipin and antiphosphatidylserine antibodies in
      IVF patients was 7.0% and 11.2%, respectively. There was no statistically
      significant difference in the prevalence of these antibodies in the groups of
      patients with a biochemical pregnancy (0 for anticardiolipin and 2.8% for
      antiphosphatidylserine), spontaneous miscarriage (11.4% for anticardiolipin and
      20% for antiphosphatidylserine), ongoing pregnancy (7.3% for anticardiolipin and
      11.6% for antiphosphatidylserine), and patients who failed to conceive (7.2% for
      anticardiolipin and 10.8% for antiphosphatidylserine). There was no correlation
      between outcome and the antibody isotype expressed. CONCLUSION(S):
      Anticardiolipin and antiphosphatidylserine antibodies are poorly predictive of
      the IVF cycle outcome. Routine testing of IVF patients for the presence of these
      antibodies is of limited clinical utility.

PMID- 9240263
TI  - Incubation with sperm enhances in vitro maturation of the oocyte from the
      germinal vesicle to the M2 stage.
AB  - OBJECTIVE: To evaluate the effect of sperm in the culture medium on the rate of
      oocyte maturation in vitro from the germinal vesicle to the M2 stage. DESIGN:
      Prospective randomized controlled study. SETTING: The IVF Unit, Wolfson Medical
      Center, Holon, Israel. PATIENT(S): All women in whom oocytes were retrieved at
      the germinal vesicle stage between December 1995 and March 1996. INTERVENTION(S):
      Oocytes retrieved at the germinal vesicle stage were divided prospectively and
      randomly into four groups of incubation conditions: group 1, intact germinal
      vesicle with cumulus; group 2, intact germinal vesicle with sperm cells in the
      culture medium; group 3, stripped germinal vesicle; and group 4, stripped
      germinal vesicle with sperm cells. Oocytes were observed 24 hours after
      retrieval, and the stage of maturation was recorded. Oocytes that reached the M2
      stage underwent the intracytoplasmic injection procedure, and the fertilization
      rate in each group was recorded at 48 hours. MAIN OUTCOME MEASURE(S): Maturation
      rate from the germinal vesicle to M2 stage and fertilization rate. RESULT(S):
      Each group contained 20 germinal vesicle oocytes. In groups 1 and 2, 2 (10%) and
      9 (45%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 1
      (5%) and 8 (40%) embryos developed, respectively. The results in group 2 were
      significantly higher than in group 1. In groups 3 and 4, 6 (30%) and 16 (80%)
      oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 5 (25%) and
      14 (70%) embryos developed, respectively. Results in group 4 were significantly
      higher than those in groups 1, 2, and 3. CONCLUSION(S): Both methods of oocyte
      activation (i.e., addition of sperm to the culture medium or removal of the
      cumulus) enhance oocyte maturation in vitro, but the sperm-incubation method has
      a more pronounced effect. A combination of both methods leads to an exceptionally
      high rate of oocyte maturation, followed by a high fertilization rate.

PMID- 9240261
TI  - Vascular endothelial growth factor levels in serum and follicular fluid of
      patients undergoing in vitro fertilization.
AB  - OBJECTIVE: To define the relationship between serum and follicular fluid (FF)
      levels of vascular endothelial growth factor (VEGF), E2, and P in patients
      undergoing IVF; to quantify the effects of hCG on serum levels of VEGF during
      early pregnancy, and to report serial measurements of serum and ascites fluid
      levels of VEGF in a patient with severe ovarian hyperstimulation syndrome (OHSS).
      DESIGN: Prospective observational study. SETTING: University IVF program.
      PATIENTS(S): Women undergoing conventional IVF, receiving donated oocytes or
      spontaneously conceiving. One patient hospitalized with severe OHSS. MAIN OUTCOME
      MEASURE(S): Concentrations of VEGF, E2, and P in serum, FF, or peritoneal fluid.
      RESULT(S): At the time of egg retrieval, FF VEGF concentrations were positively
      correlated with serum and FF P concentrations and with patient age. At 11 to 14
      days after ET, pregnant recipients of autologous fresh embryos had higher serum
      VEGF levels than both nonpregnant recipients of autologous fresh embryos and
      pregnant recipients of donor eggs. Elevated serum VEGF levels in a patient with
      severe OHSS coincided with the clinical onset and recurrence of symptoms.
      CONCLUSION(S): In patients undergoing IVF, FF VEGF levels at the time of egg
      retrieval correlated with the degree of follicular luteinization. There is a
      significant ovarian contribution to circulating VEGF levels during early
      gestation. Elevated serum VEGF levels may be a factor in the etiology of OHSS
      symptoms.

PMID- 9240262
TI  - The incidence of apoptotic bodies in membrana granulosa can predict prognosis of
      ova from patients participating in in vitro fertilization programs.
AB  - OBJECTIVE: To investigate the relationship between the incidence of apoptotic
      bodies in membrana granulosa and follicular steroid concentrations in human
      follicles. DESIGN: Case-controlled prospective study for 132 individual
      follicles. SETTING: Procedures were performed in Yamagata University Hospital.
      PATIENT(S): Thirty-six normo-ovulatory women with tubal infertility underwent
      ovulation induction for IVF-ET with a conventional hyperstimulation method.
      INTERVENTION(S): Patients underwent follicle aspiration after the administration
      of hCG. MAIN OUTCOME MEASURE(S): The nuclei of recovered granulosa cells were
      examined by fluorescence microscopy, and the incidence of apoptotic bodies was
      tabulated. Intrafollicular steroids were evaluated mainly by RIA. These data were
      analyzed with respect to oocyte-retrieval, oocyte maturity, fertilization, and
      embryo quality. RESULT(S): Membrana granulosa cells in the follicles from which
      oocytes were subsequently fertilized showed a significantly lower incidence of
      apoptotic bodies than those in follicles from which the oocytes did not
      fertilize. Membrana granulosa cells in the follicles from which oocytes were
      developed into good quality showed a significantly lower incidence of apoptotic
      bodies than those in the follicles from which oocytes developed into fair and
      poor quality. The incidence of apoptotic bodies was significantly higher in the
      mural granulosa cell region than in the cumulus cell region in most cases.
      Intrafollicular E2, P, and free T levels were not different between the oocyte
      groups. CONCLUSION(S): These results indicate that lower incidence of apoptotic
      bodies in individual follicles is associated with better outcomes for oocytes.
      Also, mural granulosa cells and cumulus cell in each follicle may show
      differentiation during follicular maturation.

PMID- 9240264
TI  - Some psychological aspects of oocyte donation from known donors on altruistic
      basis.
AB  - OBJECTIVE: To survey a sample of couples along with their chosen oocyte donors
      regarding psychological variables. DESIGN: Patients in an infertility clinic were
      interviewed by a counselor using a semistructured interview format designed to
      gather systematic data. SETTING: Infertility clinic. PATIENT(S): Ten recipient
      couples along with their donors were seen. RESULT(S): Oocyte recipients ranged in
      age from 30 to 49 years with a mean age of 40 years. Oocyte donors ranged in age
      from 21-34 years with a mean age of 29 years. Eighty percent of donors were
      married or involved in a serious relationship; 90% of donors had at least one
      child. The major reason for acting as a donor was altruism. Anonymity was a
      primary concern for recipients and donors: 80% of the sample had not confided in
      anyone at the present time. 70% did not intend to disclose any information at any
      time; 80% did not plan to inform the child, while 20% were undecided at the
      present time; and 90% indicated good to excellent support systems. CONCLUSION(S):
      The present study provides significant information regarding Canadian couples
      undergoing the oocyte donation program with known donors.

PMID- 9240265
TI  - Testicular sperm extraction and intracytoplasmic sperm injection: a simplified
      method for treatment of obstructive azoospermia.
AB  - OBJECTIVE: To assess the effectiveness of a simple method of testicular sperm
      extraction for the treatment of obstructive azoospermia. DESIGN: Retrospective
      study. SETTING: Teaching tertiary medical center. PATIENT(S): Seventeen men with
      obstructive azoospermia. INTERVENTION(S): The patients underwent 19 cycles of
      intracytoplasmic sperm injection (ICSI) using testicular sperm. In 5 cycles,
      testicular sperm extraction was performed after failed microepididymal sperm
      aspiration. In 14 cycles, testicular sperm extraction was performed in the office
      under local anesthesia from the outset. The outcome was compared with ICSI cycles
      using ejaculated sperm (95 cycles) and epididymal sperm (12 cycles fresh and 9
      cycles frozen-thawed). MAIN OUTCOME MEASURE(S): Clinical pregnancy and
      implantation rates. RESULT(S): There were no differences in the fertilization,
      cleavage, implantation, or clinical pregnancy rates among ICSI cycles using
      testicular, epididymal (fresh or frozen-thawed), or ejaculated sperm.
      CONCLUSION(S): When used in conjunction with ICSI, testicular sperm extraction
      from small excisional biopsy is a simple and cost-effective method for the
      treatment of obstructive azoospermia.

PMID- 9240267
TI  - The performance of 10 different methods for the estimation of sperm
      concentration.
AB  - OBJECTIVE: To evaluate the performance of different methods of sperm counting
      using latex beads and sperm suspension. DESIGN: A quality-control study. SETTING:
      University-based andrology laboratory. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Counting latex beads six times in two standard suspensions using 10
      methods and counting spermatozoa with 4 methods. RESULT(S): When air-displacement
      pipettes were used, the disposable chambers Standard Count (Leja, Amsterdam,
      Holland), Cellvision (Anthos-ec, Heerhugowaard, The Netherlands), and Cell Vu
      (Fertility Technologies, Inc. Natick, MA) showed small variation and correct
      estimation of bead concentration. All the reusable chambers gave relatively large
      variability, with tendency to underestimate (improved Neubauer; Hawksley,
      Lancing, United Kingdom) or to overestimate the bead concentration. The use of
      plunger-displacement pipettes resulted in an overestimation of bead concentration
      in medium but not in seminal plasma. Counting the sperm suspension using plunger
      displacement pipettes indicated that the Burker hemocytometer overestimated
      concentration relative to that obtained by Cellvision and Makler Counting
      Chambers (Sefi Medical Instruments, Haifa, Israel) and that the improved Neubauer
      presented the lowest variability (7.1%). CONCLUSION(S): The improved Neubauer
      hemocytometer is the standard for sperm counting, though disposable chambers give
      reliable results as well. If beads are used to evaluate the accuracy of counting
      chambers, it is recommended to dilute them with seminal plasma.

PMID- 9240266
TI  - Effect of increased scrotal temperature on sperm production in normal men.
AB  - OBJECTIVE: To determine whether application of polyester-lined athletic supports
      to bring the testes closer to the abdomen increases scrotal temperature and
      decreases sperm production. DESIGN: Prospective clinical study. SETTING:
      University academic medical center. PATIENT(S): Twenty-one healthy male
      volunteers. INTERVENTION(S): The study consisted of a pretreatment period of 6
      weeks, a treatment phase of 52 weeks, and a recovery phase until return to normal
      sperm production. During the treatment phase, the men wore polyester-lined
      athletic supports (single layer, double layer, or double layer impregnated with
      aluminum) throughout the day. MAIN OUTCOME MEASURE(S): Semen parameters and sperm
      function tests. RESULT(S): In all three groups of subjects, scrotal temperature
      was consistently increased by 0.8 to 1 degree C while the subjects were wearing
      the athletic supports. Mean sperm concentration; sperm motility, morphology, and
      viability; sperm hyperactivation; and ability of spermatozoa to penetrate zone
      free hamster oocytes were not affected by the increase in scrotal temperature.
      CONCLUSION(S): The increase in scrotal temperature induced by polyester-lined
      athletic supports was insufficient to cause significant suppression of
      spermatogenesis or alteration of sperm function.

PMID- 9240268
TI  - The single sperm curling test, a modified hypo-osmotic swelling test, as a
      potential technique for the selection of viable sperm for intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To develop a technique for the selection of viable sperm for
      intracytoplasmic sperm injection (ICSI), based on the phenomenon of sperm tail
      curling in a hypo-osmotic environment, through modification of the hypo-osmotic
      swelling test. DESIGN: Individual sperm were exposed to single sperm curling
      (SSC) medium and then injected into hamster oocytes to study the effect of SSC
      medium on fertilization. SETTING: All materials were collected from the National
      University Hospital in Singapore. PATIENT(S): Semen of proven donors and hamster
      oocytes with intact zonae were used. INTERVENTION(S): ICSI and the SSC test. MAIN
      OUTCOME MEASURE(S): Sperm head decondensation and male pronucleus formation.
      RESULT(S): Sperm head decondensation and male pronucleus formation were present
      in 59.4% and 42.4%, respectively, of the oocytes injected with sperm that had
      been exposed to SSC medium. These rates were 70% and 48.8%, respectively, when
      the sperm were washed thoroughly after exposure to SSC medium. In the control
      group (sperm that were not exposed to SSC medium), these rates were 68.8% and
      46.2%, respectively. CONCLUSION(S): The SSC test is useful for the selection of
      viable sperm for ICSI. It allows the behavioral study of a single sperm in hypo
      osmotic conditions. Thorough washing of the exposed sperm is important. This
      procedure would be of benefit especially in testicular biopsies or very severe
      cases of low sperm count in which only a few sperm are found among many other
      cells and artifact.

PMID- 9240269
TI  - Sperm interaction with fallopian tube apical membrane enhances sperm motility and
      delays capacitation.
AB  - OBJECTIVE: To understand the effect of sperm contact with the apical plasma
      membrane of tubal epithelial cells on sperm motility, velocity, and capacitation.
      DESIGN: Prospective, controlled in vitro study. SETTING: University medical
      center. PATIENT(S): Women of reproductive age undergoing hysterectomy for benign
      gynecologic indications and normozoospermic donors of proved fertility. MAIN
      OUTCOME MEASURE(S): Sperm motility as measured manually, velocity as measured by
      computer-assisted sperm motility analysis, and capacitation status as measured by
      the chlortetracycline fluorescence assay. RESULT(S): Sperm incubated with apical
      membrane vesicles had a significantly higher motility at 12 (87.4% +/- 3.4%
      versus 69.2% +/- 4.8% [mean +/- SEM]), 24 (85.2% +/- 3.1% versus 60.5% +/- 7.2%)
      and 48 hours (78.9% +/- 5.3% versus 42.4% +/- 11.3%) compared with control (sperm
      incubated with human tubal fluid media in the absence of apical membrane
      vesicles) (n = 4). Progressive velocity was significantly higher at 12 (78.2 +/-
      1.4 versus 61.7 +/- 16.1 microns/s) and 24 (66.2 +/- 3.9 versus 34.4 +/- 9.8
      microns/s) hours (n = 4). Incubation with apical membrane vesicles significantly
      slowed the transition from uncapacitated to capacitated chlortetracycline
      fluorescence pattern (n = 5). CONCLUSION(S): Contact with the apical plasma
      membrane of tubal epithelial cells enhances sperm motility and delays sperm
      capacitation in vitro.

PMID- 9240270
TI  - Dietary carrot results in diminished ovarian progesterone secretion, whereas a
      metabolite, retinoic acid, stimulates progesterone secretion in the in vitro
      perfused rabbit ovary.
AB  - OBJECTIVE: To determine the effects of dietary carrots and retinoic acid on P
      secretion in the in vitro perfused rabbit ovary. DESIGN: Controlled experiment.
      SETTING: Laboratory. SUBJECTS: Sexually mature New Zealand white rabbits.
      INTERVENTION(S): Experiments were done in vitro using an isolated rabbit ovarian
      perfusion system after acute feeding of carrots or with in vitro exposure to
      retinoic acid. MAIN OUTCOME MEASURE(S): Progesterone and E2 were measured in
      aliquots taken from arterial and venous cannulas. RESULT(S): Progesterone
      secretion during the in vitro perfusion of six ovaries is significantly
      diminished after the acute feeding of carrots. Human chorionic gonadotropin
      induced P secretion also is significantly reduced. Progesterone secretion during
      in vitro perfusion on day 1 of pseudopregnancy was significantly increased in the
      perfusate samples from ovaries taken from rabbits not acutely fed carrots but
      that were exposed to retinoic acid. Progesterone secretion was increased but only
      marginally significant on day 11 of pseudopregnancy in perfusate samples from
      ovaries exposed to retinoic acid. CONCLUSION(S): Rabbit ovarian P secretion may
      be modified by carrots and carotene metabolites. This effect on steroid secretion
      may contribute to the relationship between hypercarotenemia and alterations in
      menstrual function.

PMID- 9240271
TI  - Accidental ovarian autograft after a laparoscopic surgery: case report.
AB  - OBJECTIVE: To report an autograft of ovarian tissue in the incision of the
      surgical trocar during laparoscopic surgery and to assess the potentiality of
      grafting of ovarian parenchyma in nonpelvic tissue in humans. DESIGN: A case
      report. SETTING: Instituto de Fertilidad y Ginecologia de Buenos Aires (IFER),
      Buenos Aires, Argentina. PATIENT(S): Infertile patient undergoing surgery due to
      an endometriotic cyst of the left ovary. INTERVENTION(S): Laparoscopic
      cystectomy. Accidental retention of a portion of the capsule and adjacent ovarian
      tissue of the endometrioma in SC cellular tissue. Months after surgery, a SC
      tumor was formed under the surgical incision. It was subsequently excised. MAIN
      OUTCOME MEASURE(S): Observation of tumor growth during menstrual cycles and
      ovulation induction; anatomopathologic study of the tissue after its extirpation.
      RESULT(S): The tumor grew spontaneously in the periovulatory period and during
      treatments of ovulation induction. The anatomopathologic report of the tumor,
      removed 15 months after the first surgery, revealed functioning ovarian tissue
      with vessels of neoformation. CONCLUSION(S): This is the first description of
      autografted ovarian tissue in humans. We describe that the ovary can maintain its
      ovulatory function even in the absence of its pedicel. Also, we suggest that
      extirpation of surgical material through the incision of the trocar is not
      recommended, as the possibility of "sowing" or of autografts may occur.

PMID- 9240272
TI  - Successful birth after intrafallopian transfer of microhatched embryos.
AB  - OBJECTIVE: To present a successful transfer of microhatched embryos to the
      fallopian tubes via microlaparoscopy. DESIGN: Case report. SETTING: Private
      practice affiliated with a medical university. PATIENT: A 40-year-old woman with
      primary infertility, mildly elevated baseline FSH levels, and a history of poor
      ovarian response to ovulation induction. Her husband had severe oligoospermia
      after vasectomy reversal. INTERVENTION(S): Late luteal leuprolide acetate to
      pituitary down-regulation followed by pure FSH, 300 IU, and hMG, 300 IU, daily
      for ovulation induction. Transvaginal oocyte retrieval, intracytoplasmic sperm
      injection, assisted embryo hatching, microlaparoscopic intrafallopian ET. MAIN
      OUTCOME MEASURE(S): Amniocentesis at the 14th week of gestation revealed a normal
      karyotype (46,XX), birth of a normal female infant (3700 g). RESULT(S):
      Establishment of a single, viable intrauterine gestation followed by a vaginal
      delivery at term. CONCLUSION(S): This case shows the possibility of using
      assisted-hatched embryos for laparoscopic intrafallopian tube transfer.

PMID- 9240273
TI  - The impact of an egg donor's age and her prior fertility on recipient pregnancy
      outcome.
AB  - OBJECTIVE: To investigate the effect of donor's age and her prior fertility on
      recipient pregnancy outcome in our donor egg program. DESIGN: Retrospective
      cohort analysis. SETTING: Large academic infertility center. PATIENT(S): A total
      of 568 fresh ETs were analyzed for the effect of the egg donor's age on pregnancy
      outcome; a subset of these (n = 185) were analyzed for the effect of the egg
      donor's prior fertility on pregnancy outcome. INTERVENTION(S): Donors were paired
      with recipients independent of recipient's age and donor's prior fertility
      status. MAIN OUTCOME MEASURE(S): Recipient clinical pregnancy rates (PRs) and
      delivery rates for different donor age groups and for nulligravid donors versus
      donors with proven fertility. RESULT(S): Donors > or = 33 years old were less
      likely than younger donors to produce clinical pregnancies and deliveries in
      their recipients (43.5% versus 26.6% and 35.1% versus 22.1%, respectively).
      However, there was no difference in clinical PRs or delivery rates between
      nulligravid donors and donors with proven fertility. CONCLUSION(S): Donors > or =
      33 years of age could be excluded from egg donation because of the lower
      pregnancy potential of their eggs. However, lack of proven fertility in a donor
      seems to have no negative impact on pregnancy potential.

PMID- 9240274
TI  - High fertilization rate obtained after intracytoplasmic sperm injection with 100%
      nonmotile spermatozoa selected by using a simple modified hypo-osmotic swelling
      test.
AB  - OBJECTIVE: To report a high fertilization rate after intracytoplasmic sperm
      injection (ICSI) in patients with 100% nonmotile spermatozoa selected by a simple
      modified hypo-osmotic swelling test. DESIGN: Clinical study. SETTING: Hospital
      based IVF center. PATIENT(S): Three couples with infertility due to
      asthenospermia. INTERVENTION(S): The hypo-osmotic swelling test with 150-mOsm
      NaCl solution was used to select viable spermatozoa before ICSI. Three patients
      provided semen samples and one of these three also had a testicular biopsy. MAIN
      OUTCOME MEASURE(S): Selection of viable spermatozoa using the hypo-osmotic
      swelling test with 150-mOsm NaCl solution for ICSI. RESULT(S): No motile
      spermatozoa were found in three ejaculated semen samples and one testicular
      biopsy. Fifty-seven metaphase-II oocytes were injected with hypo-osmotic swelling
      test-positive ejaculated or testicular spermatozoa. Fifty-five (96.5%) of these
      oocytes were intact after injection. Forty-two (76.4%) of 55 oocytes showed two
      pronuclei, and 40 of the 42 fertilized oocytes cleaved. One patient had all
      embryos cryopreserved because of the risk of hyperstimulation; two other patients
      had embryos transferred. One ongoing pregnancy resulted. CONCLUSION: This hypo
      osmotic swelling test with 150-mOsm NaCl solution is a simple and efficient
      method for selection of viable spermatozoa. A high fertilization rate can be
      obtained using ICSI with viable spermatozoa selected by using this hypo-osmotic
      swelling test.

PMID- 9240275
TI  - An improved treatment procedure for testicular biopsy specimens offers more
      efficient sperm recovery: case series.
AB  - OBJECTIVE: To report an improved sperm recovery procedure from testicular biopsy
      specimens for intracytoplasmic sperm injection (ICSI). DESIGN: Case series and
      controlled study. SETTING: Procedures were performed in a tertiary IVF center.
      PATIENT(S): Nonobstructive azoospermic cases (15 patients) and obstructive
      azoospermic cases (5 patients). INTERVENTION(S): Intracytoplasmic sperm injection
      was carried out using testicular sperm isolated from a testicular biopsy specimen
      either with or without erythrocyte lysing buffer treatment. MAIN OUTCOME
      MEASURE(S): The time required to collect spermatozoa and the intactness and
      fertilization and developmental rates of oocytes. RESULT(S): In 7 of the 15
      nonobstructive cases, it was possible to perform ICSI when, after shredding of
      the testicular tissue, no (or virtually no) sperm were present. There was no
      difference in the fertilization rates (83% and 68%) and developmental rates (87%
      and 89%) of the 54 sibling oocytes from another 5 patients in whom ICSI was
      carried out with sperm either treated or not treated with erythrocyte lysing
      buffer. CONCLUSION(S): Erythrocyte lysing buffer treatment of testicular biopsy
      specimens enhances the efficiency of sperm collection in those cycles in which
      spermatozoa are present and does not affect fertilization and embryo development.

PMID- 9240276
TI  - Gonadotropins and sex selection?

PMID- 9240277
TI  - Observer variation and clinical decision making.

PMID- 9240278
TI  - Stress and infertility: "the chicken or the egg?".

PMID- 9240279
TI  - Packaging--California style.

PMID- 9240280
TI  - Obstetricians' receptiveness to teen prenatal patients who are Medicaid
      recipients.
AB  - OBJECTIVE: To test the accuracy of various physicians' participation in Medicaid
      models. DATA SOURCES/STUDY SETTING: Primary data on 221 obstetricians and
      gynecologists in the Chicago area by telephone interviews over a four-month
      period. These data were combined with secondary data from the American Medical
      Association Master File (1993) and U.S. Census data (1990). STUDY DESIGN:
      Telephone interviewers posing as the older sisters of a pregnant teenager who is
      a Medicaid recipient sought information regarding the care provided in a first
      prenatal care appointment (e.g., appointment duration, tests administered,
      delivery privileges, appointment availability). DATA COLLECTION/EXTRACTION
      METHODS: A "receptionist helpfulness" variable was developed through pretesting
      on obstetricians in another city. Inter-interviewer reliability was enhanced
      through common interview technique education. PRINCIPAL FINDINGS: Only 81
      obstetricians (36.7 percent) accepted new Medicaid patients. This finding is
      lower than previous research on physician participation in Medicaid. There was
      strong empirical support for both dimensions-cost containment and limited access
      of the physicians' receptiveness model, the model introduced with this research.
      There was limited support for the dual market and residential segregation models
      of physician participation in Medicaid. CONCLUSIONS: It is argued that this
      study's research design is more accurate in reflecting the barriers that a
      pregnant Medicaid-eligible patient encounters when seeking office-based prenatal
      care. As such, combining the physicians' receptiveness model with other physician
      participation in Medicaid models provides a more complete picture of access
      barriers to prenatal care for our most needy populations.

PMID- 9240281
TI  - Physician behavioral response to a Medicare price reduction.
AB  - OBJECTIVE: To investigate at the individual practice level physician behavioral
      responses to the Medicare fee reductions mandated in the Omnibus Budget
      Reconciliation Act of 1989. Symmetric and nonsymmetric behavioral responses are
      modeled and investigated. DATA SOURCES: Volume index calculated from data in the
      Part B Medicare Annual Data (BMAD) Provider Files for 1989 and 1990. The pricing
      data are from the Procedure Files. STUDY DESIGN: A fixed-effects model in carrier
      and in specialty is employed. DATA COLLECTION: No direct data collection is
      required as BMAD files are used in the study. Price and volume variables are
      expressed as Fisher indexes of change. PRINCIPAL FINDINGS: The results show
      nonsymmetrical behavioral response because practices that did not face
      significant fee reductions do not exhibit behavioral change. By contrast, losers
      partially compensate for the fee reductions. For every dollar cut in their fees,
      physicians recoup approximately 40 cents by increasing volume. Loser behavioral
      responses vary by specialty. CONCLUSIONS: The presence of a volume response
      suggests that price control alone is not sufficient to cap rising healthcare
      costs. This indicates that additional or other tools must be considered if cost
      containment is to be attained.

PMID- 9240282
TI  - Physician variations and the ancillary costs of neonatal intensive care.
AB  - OBJECTIVE: To determine to what degree attending physicians contribute to cost
      variations in the care of ventilator-dependent newborns. DATA SOURCES: Clinical
      data were merged with hospital financial data describing daily ancillary care
      costs during the first two weeks of life for 132 extremely low-birthweight
      newborns. In addition, each patient's chart was reviewed and illness severity
      graded using both SNAP and CRIB scores. STUDY DESIGN: This was a retrospective
      cohort of infants with birth weights of less than 1,001 grams and respiratory
      distress syndrome requiring mechanical ventilation in the first day of life. From
      birth up to two weeks of life, each received care directed by only one of 11
      faculty neonatologists in a single university hospital. Data were analyzed
      stratified by these physicians. t-Test, ANOVA, and chi-square were used to assess
      bivariate data. For continuous data, log linear regressions were used. PRINCIPAL
      FINDINGS: After controlling for illness severity, when stratified by physicians,
      there were significant variances in the costs of ancillary resources for the
      study infants (p < .0001). Twenty-nine percent of the variance was attributable
      to whether or not the hospital day included the use of a ventilator. Physician
      identity explained only 5.6 percent (p < .0001). CONCLUSIONS: Physician identity
      was significant but explained less than 6 percent of the total variance in
      ancillary costs. Whether or not a ventilator was used during care was far more
      important. We conclude that for very sick babies during the first two weeks of
      care, reducing variations in ancillary services utilization among neonatologists
      will yield only modest savings.

PMID- 9240283
TI  - An empirical study of economies of scope in home healthcare.
AB  - OBJECTIVE: To apply the economic theory of economies of scope to the home
      healthcare industry. DATA SOURCES: Data on 488 observations obtained from the
      Cost Report (HCFA Form 1728-86) of all Connecticut state-licensed, Medicare
      certified home health agencies. STUDY DESIGN: The Cost Report was the primary
      source of data for this study. Information on total cost, scope, and other
      related factors was collected. Logarithmic and nonlinear regression analyses were
      used to identify factors related to scope and also to test for economies of
      scope. DATA COLLECTION METHOD: Data collected were both cross-sectional and time
      series (from 1988-1992). Data accuracy was verified using description of
      frequencies, measures of central tendency and variation, and a calculation
      package so that a computer calculation on the data could be compared with the
      agency's calculation. PRINCIPAL FINDINGS: It was determined that initially as
      scope increases, costs go down, thus proving economies of scope. For larger
      values of scope, it was determined that costs go up, proving diseconomies of
      scope. CONCLUSIONS: Many of the home health agencies included in this study
      provide more services than is cost effective given the economic theory of
      economies of scope.

PMID- 9240284
TI  - Influence of projected complication rates on estimated appropriate use rates for
      carotid endarterectomy. Appropriateness Project Investigators. Academic Medical
      Center Consortium.
AB  - OBJECTIVE: To examine specifically the influence of estimated perioperative
      mortality and stroke rate on the assessment of appropriateness of carotid
      endarterectomy. DATA SOURCES/STUDY SETTING: An expert panel convened to rate the
      appropriateness of a variety of potential indications for carotid endarterectomy
      based on various rates of perioperative complications. We then applied these
      ratings to the charts of 1,160 randomly selected patients who had carotid
      endarterectomy in one of the 12 participating academic medical centers. STUDY
      DESIGN: An expert panel evaluated indications for carotid endarterectomy using
      the modified Delphi approach. Charts of patients who received surgery were
      abstracted, and clinical indications for the procedure as well as perioperative
      complications were recorded. To examine the impact of surgical risk assessment on
      the rates of appropriateness, three different definitions of risk strata for
      combined perioperative death or stroke were used: Definition A, low risk < 3
      percent; Definition B, low risk < 5 percent; and Definition C, low risk < 7
      percent. PRINCIPAL FINDINGS: Overall hospital-specific mortality ranged from 0
      percent to 4.0 percent and major complications, defined as death, stroke,
      intracranial hemorrhage, or myocardial infarction, varied from 2.0 percent to
      11.1 percent. Most patients (72 percent) had surgery for transient ischemic
      attack or stroke; 24 percent of patients were asymptomatic. Most patients (82
      percent) had surgery on the side of a high-grade stenosis (70-99 percent). When
      the thresholds for operative risk were placed at the values defined by the expert
      panel (Definition A), only 33.5 percent of 1,160 procedures were classified as
      "appropriate." When the definition of low risk was shifted upward, the proportion
      of cases categorized as appropriate increased to 58 percent and 81.5 percent for
      Definitions B and C, respectively. CONCLUSIONS: Despite the high proportion of
      procedures performed for symptomatic patients with a high degree of ipsilateral
      extracranial carotid artery stenosis and generally low rates of surgical
      complications at the participating institutions, the overall rate of
      "appropriateness" using a perioperative complication rate of < 3 percent was low.
      However, the rate of "appropriateness" was extremely sensitive to judgments about
      a single clinical feature, surgical risk. These data show that before applying
      such "appropriateness" ratings, it is crucial to perform sensitivity analyses in
      order to assess the stability of the results. Results that are robust to moderate
      in variation in surgical risk provide a much sounder basis for policy making than
      those that are not.

PMID- 9240286
TI  - Comparison of responses to SF-36 Health Survey questions with one-week and four
      week recall periods.
AB  - OBJECTIVE: To compare the measurement properties of acute (one-week recall) and
      standard (four-week recall) versions of SF-36 Health Survey (SF-36) scale scores.
      DATA SOURCES: SF-36 data collected from 142 participants (60% female, average age
      39) in a clinical trial of an asthma medication: 74 patients randomized to the
      acute form and 68 to the standard. DATA COLLECTION: The SF-36 was self
      administered at the time of a clinic visit (before clinical examination) to
      synchronize with clinical measures of disease severity at three different time
      points during the clinical trial: -2 weeks (two weeks before randomization to
      treatment), baseline (week 0 or randomization), and +4 weeks (four weeks after
      baseline). PRINCIPAL FINDINGS: The acute form yielded high-quality data; scales
      conformed to the assumptions of the summated ratings method used to score the
      standard SF-36; and scales had good distributional properties, were reliable, and
      had a factor content similar to the standard. The data indicated that while the
      acute form was more sensitive than the standard to change in health status
      associated with changes in acute symptoms, acute scale scores may not be
      comparable to national norms based on the standard, particularly for those scales
      that assess frequency of health events during a specified time period.
      CONCLUSIONS: Results support the use of the acute form in its intended
      applications; however, further research is required to document the
      generalizability of greater sensitivity of the acute form to recent changes in
      health and to explore whether norms based on the standard can be used to
      interpret the acute scale scores.

PMID- 9240285
TI  - Nonmedical influences on medical decision making: an experimental technique using
      videotapes, factorial design, and survey sampling.
AB  - OBJECTIVE: To study nonmedical influences on the doctor-patient interaction. A
      technique using simulated patients and "real" doctors is described. DATA SOURCES:
      A random sample of physicians, stratified on such characteristics as
      demographics, specialty, or experience, and selected from commercial and
      professional listings. STUDY DESIGN: A medical appointment is depicted on
      videotape by professional actors. The patient's presenting complaint (e.g., chest
      pain) allows a range of valid interpretation. Several alternative versions are
      taped, featuring the same script with patient-actors of different age, sex, race,
      or other characteristics. Fractional factorial design is used to select a
      balanced subset of patient characteristics, reducing costs without biasing the
      outcome. DATA COLLECTION: Each physician is shown one version of the videotape
      appointment and is asked to describe how he or she would diagnose or treat such a
      patient. PRINCIPAL FINDINGS: Two studies using this technique have been completed
      to date, one involving chest pain and dyspnea and the other involving breast
      cancer. The factorial design provided sufficient power, despite limited sample
      size, to demonstrate with statistical significance various influences of the
      experimental and stratification variables, including the patient's gender and age
      and the physician's experience. Persistent recruitment produced a high response
      rate, minimizing selection bias and enhancing validity. CONCLUSION: These
      techniques permit us to determine, with a degree of control unattainable in
      observational studies, whether medical decisions as described by actual
      physicians and drawn from a demographic or professional group of interest, are
      influenced by a prescribed set of nonmedical factors.

PMID- 9240287
TI  - Hemodynamic effect of progressive right atrial dilatation in atriopulmonary
      connections.
AB  - OBJECTIVE: Right atrial dilation occurring late after the modified Fontan
      procedure is frequently associated with low output states, supraventricular
      arrhythmias, and atrial thrombus formation. We addressed the hypothesis that
      progressive right atrial dilatation contributes to inefficient right heart flow
      dynamics. METHODS: Modified atriopulmonary connections were performed on
      explanted isolated sheep heart preparations with various degrees of surgically
      induced right atrial dilatation (right atrial volumes 6 to 55 cm3). Flow models
      were perfused in an in vitro flow loop with the use of a blood analog fluid. A
      fluid energy balance was performed for six flow rates (1.0 to 6.0 L/min) at each
      degree of right atrial dilatation, and the rate of total fluid energy loss was
      calculated and expressed as a function of right atrial volume and flow rate.
      Effective pressure drop and fluid resistance across the right atrial chamber were
      also determined for each flow condition. RESULTS: The rate of fluid energy loss
      increased with increasing right atrial dilatation and flow rate for all
      conditions studied (p < 0.001). Over the range of right atrial volumes and flow
      rates examined, the average increase in the rate of energy loss was 3.8- and 117
      fold, respectively. Calculated fluid resistance through the right atrium also
      increased with increasing right atrial volume and flow rate (p < 0.001),
      exhibiting an average increase of 3.2- and 3.3-fold respectively. CONCLUSIONS:
      Right atrial dilatation in atriopulmonary connections causes fluid energy losses
      and increases the energy required to move blood from the venae cavae to the
      pulmonary arteries. These observations may help explain the progressive nature of
      late failures of atriopulmonary connections and provide additional rationale for
      conversion from atriopulmonary connections to lateral tunnel total cavopulmonary
      connections in selected patients.

PMID- 9240288
TI  - The parachute-like asymmetric mitral valve and its two papillary muscles.
AB  - OBJECTIVES: The morphologic features of parachute-like asymmetric mitral valves
      are described to discriminate this anomaly from parachute mitral valves.
      BACKGROUND: Mitral valves with unifocal attachment of chords have been called
      "parachute valves," independent of the number of papillary muscles. Therefore the
      anomaly involving two papillary muscles has not received separate attention.
      METHODS: The gross anatomy of 29 mitral valves with focalized attachment of
      chords was studied. RESULTS: In 28 of the autopsy specimens asymmetric mitral
      valves with two papillary muscles were present, and one of the muscles was
      elongated, located higher in the left ventricle with its tip reaching to the
      anulus, and attached at both its base and lateral side to the left ventricular
      wall. The valve leaflets could be directly attached to this abnormal muscle that
      received few chords or, in three hearts, no chords at all, resulting in an
      oblique and eccentric orifice. Because of the focalized attachment of chords to
      one of the two papillary muscles, we call this malformation "parachute-like
      asymmetric mitral valve," We found only one "true parachute mitral valve," that
      is, one having a single papillary muscle that received all chords. CONCLUSIONS:
      The morphologic features of asymmetric mitral valves are essentially different
      from those of true parachute valves. A distinction between these two anomalies
      will contribute to recognition by the pediatric cardiologist and surgeon.

PMID- 9240289
TI  - The aortic root in supravalvular aortic stenosis: the potential surgical
      relevance of morphologic findings.
AB  - OBJECTIVE: We aimed to elucidate the structural basis of supravalvular aortic
      stenosis in the context of its surgical repair. METHODS: We examined
      retrospectively the angiograms and echocardiograms of 37 patients and compared
      them with those of control groups. Additionally, we studied 8 pathologic
      specimens. RESULTS: Partial adhesion of the leaflets to the stenosing ridge was
      observed in 54% of the cases and the leaflets were thickened and less mobile in
      30%. Forty-five percent of the angiograms showed evidence of coronary orificial
      stenosis. The sinuses of Valsalva were significantly enlarged in 75% of the
      cases. Changes in dimensions of the aortic root were demonstrated more clearly by
      angiography than by echocardiography. In all anatomic specimens, a marked
      redundancy of the leaflets was observed and quantified. CONCLUSIONS: Our data
      demonstrate that the entire valvular apparatus is always affected by the so
      called supravalvular stenosis. Anatomic restoration of the aortic root should
      ideally take into account all of the deformed components by enlarging all three
      sinuses of Valsalva at the sinotubular junction.

PMID- 9240290
TI  - The modified Blalock-Taussig shunt: clinical impact and morbidity in Fallot's
      tetralogy in the current era.
AB  - BACKGROUND: The Blalock-Taussig shunt is considered a low-risk management option
      for palliation in tetralogy of Fallot, but the morbidity associated with a
      Blalock-Taussig shunt can have a significant impact on patient care. We reviewed
      the outcome for this operation in the current era. METHODS: Between 1990 and
      1994, 65 children with tetralogy of Fallot received a modified Blalock-Taussig
      shunt. Sixty patients who had follow-up angiography were assessed for clinical
      outcomes and shunt-related morbidity and mortality. From the same study period,
      68 of 247 pediatric patients who underwent angiography and tetralogy repair, but
      did not receive palliation, were randomly selected to comprise a comparison
      group. RESULTS: Palliation was more likely in the presence of a complicated
      tetralogy malformation or if there was an associated medical condition. Median
      age at palliation was 58 days (range: 1 to 535 days). Ninety-five percent of
      shunts were right-sided. Self-limited morbidity complicated 11% of shunt
      operations. Significantly smaller distal right pulmonary arteries were observed
      in the palliated group before total repair compared with findings in the group
      without palliation and 33% of patients who underwent palliation had angiographic
      evidence of pulmonary artery distortion. Shunt stenosis was common and correlated
      with younger age at palliation. Shunt occlusion resulted in one death. Excluding
      noncardiac causes of death, overall survival was 90% in the palliated group
      versus 97% in the nonpalliated group (p = 0.09). CONCLUSIONS: Pulmonary artery
      hypoplasia and angiographic evidence of pulmonary artery distortion are common
      after initial palliation by a modified Blalock-Taussig shunt. Neonatal palliation
      was associated with significantly smaller pulmonary arteries before repair, which
      necessitated additional interventions.

PMID- 9240291
TI  - Low-dose amiodarone-related complications after cardiac operations.
AB  - OBJECTIVE: High-dose preoperative amiodarone therapy has been implicated as a
      risk factor for serious complications after cardiac operations. To investigate
      the effect of preoperative low-dose amiodarone treatment on early postoperative
      outcome after cardiac operations, we prospectively studied 88 patients. METHODS:
      Forty-four patients were receiving amiodarone (mean daily dose +/- standard
      deviation, 205 +/- 70 mg/day) and 44 patients were controls matched in pairs. The
      following parameters were recorded after the operation in all patients: (1) the
      ratio of oxygen tension to inspired oxygen fraction on arrival in the intensive
      care unit and 2, 4, 6, 10, 14, 18, and 22 hours thereafter; (2) the occurrence of
      acute respiratory distress syndrome; (3) early postoperative cardiac
      complications; and (4) the type and number of inotropic agents or vasopressors
      (or both) needed. RESULTS: No difference in the ratio of oxygen tension to
      inspired oxygen fraction was noted at the various time intervals between
      amiodarone-treated patients and control patients. Overall, only one patient had
      acute respiratory distress syndrome in the amiodarone group, but he had multiple
      other factors known to predispose to acute lung injury. Several cardiac
      complications, such as pulmonary edema, temporary pacing, and need for
      intraaortic balloon pump counterpulsation, were observed more frequently in
      amiodarone-treated patients than in control patients. In addition, amiodarone
      treated patients required more frequent inotropic support (73% vs 43%, p = 0.003)
      and more inotropic drugs or vasopressors (or both) per patient than did control
      patients (1.4 +/- 1.1 vs 0.6 +/- 0.8, p = 0.002). CONCLUSION: Preoperative low
      dose amiodarone therapy does not seem to be related to significant postoperative
      lung toxicity, but it is associated with various cardiac complications and an
      increased need for more intense inotropic support after cardiac operations. These
      findings may be related to the drug's depressant effect on the myocardium.

PMID- 9240292
TI  - Wound healing around and within saphenous vein bypass grafts.
AB  - BACKGROUND: Myofibroblasts are a prominent cell type in wound healing. The goal
      of this study was to examine the extent to which myofibroblasts contribute to
      structural changes in saphenous vein bypass grafts. METHODS AND RESULTS: Control
      veins and reversed saphenous vein bypass conduits of porcine carotid arteries
      were examined 2 to 4, 7 to 14, and 30 to 90 days after surgery with
      immunohistochemical markers of cellular proliferation (proliferating cell nuclear
      antigen), cytoskeletal protein production (alpha-smooth muscle actin and desmin),
      and histochemistry (Verhoeff's stain). Control veins demonstrated an extremely
      low level of cellular proliferation and no evidence of myofibroblasts in the
      adventitia, media, or intima. After bypass grafting, cellular proliferation was
      followed by myofibroblast formation, which occurred in the perivascular area and
      within the media. This was evidenced by a dense, but transient, expression of
      alpha-smooth muscle actin and a variable expression of desmin at 1 to 2 weeks,
      and with a significant increase in collagenous tissue by 1 to 3 months. Major
      cytoskeletal protein changes also occurred in the intima, with the appearance of
      alpha-smooth muscle actin positive cells at 7 to 14 days. alpha-Smooth muscle
      actin was still present in the neointima at 1 to 3 months, which is compatible
      with a persistent myofibroblast formation. CONCLUSION: Myofibroblast formation
      occurs around and within saphenous veins after bypass grafting. This phenomenon
      is associated with significant remodeling of the vein grafts. The histologic
      changes are strikingly similar to events that occur during wound healing and may
      have implications for the development of neointimal hyperplasia and late vein
      graft disease.

PMID- 9240293
TI  - Single and multivessel port-access coronary artery bypass grafting with
      cardioplegic arrest: technique and reproducibility.
AB  - OBJECTIVES: Although minimally invasive coronary artery bypass grafting is now
      feasible, using this technique to perform anastomoses on the beating or
      fibrillating heart may yield poorer graft patency than the standard open
      techniques that use cardioplegic arrest. This study tested the feasibility and
      anastomotic reproducibility of minimally invasive coronary bypass using newly
      developed port-access coronary artery bypass technology (Heartport, Inc., Redwood
      City, Calif.), which allows endovascular cardiopulmonary bypass, cardiac venting,
      aortic occlusion, and cardioplegic arrest for internal thoracic artery-coronary
      artery anastomoses. METHODS: Nineteen dogs had thoracoscopic takedown of either
      single (n = 14) or bilateral (n = 5) internal thoracic arteries followed by
      minimally invasive coronary bypass with cardioplegic arrest, done by means of the
      port-access system. The anastomotic technique was modified after the fourth
      animal by switching from a microscope to a 2.5 cm oval port and performing a
      conventional anastomosis with operative loupes. The adequacy of delivery of
      cardioplegic solution, ventricular decompression, and anastomotic patency was
      assessed. RESULTS: The crossclamp and bypass times were 50 +/- 15 minutes and 87
      +/- 28 minutes (mean +/- standard deviation), respectively. The mean myocardial
      temperature after cardioplegia was 17 degrees +/- 1 degree C and the aortic
      pressure (-3 +/- 9 mm Hg) and pulmonary artery pressure (4 +/- 1 mm Hg) were low
      throughout the procedure. All animals were weaned from bypass without inotropic
      agents. Angiograms and autopsies demonstrated successful thoracic artery takedown
      and anastomotic patency in 18 of 19 animals, with 100% anastomotic patency after
      the technique had been modified after the fourth animal. CONCLUSION: This study
      describes a reproducible technique for minimally invasive coronary bypass that
      allows myocardial protection, anastomotic precision, and predictable thoracic
      artery graft patency. Clinical trials are indicated.

PMID- 9240294
TI  - Controlled periadventitial administration of verapamil inhibits neointimal smooth
      muscle cell proliferation and ameliorates vasomotor abnormalities in experimental
      vein bypass grafts.
AB  - OBJECTIVE: Inhibition of early myointimal proliferation may improve longterm
      patency of vein grafts, but the clinical use of many experimental drugs is
      limited by systemic toxicity. To determine whether this goal can be achieved by
      low-dose targeted drug administration, we constructed a polymeric system
      delivering verapamil and evaluated the effects on local and downstream vein graft
      morphology, neointimal smooth muscle cell proliferation, and vasomotor function.
      METHODS: Ethylene-vinyl acetate polymeric delivery systems were constructed,
      containing 2% verapamil by weight. These are flexible, biocompatible, and
      nonbiodegradable matrices, delivering the drug at a rate of 10 micrograms/day.
      The autologous external jugular vein was used to create a carotid artery bypass
      graft in hypercholesterolemic (n = 22) rabbits. Verapamil-containing matrices (n
      = 12) or plain polymers (control, n = 10) were wrapped around the proximal third
      of the veins after reperfusion. Graft vasomotor function was evaluated and was
      also compared with function of an additional group of normocholesterolemic vein
      grafts (n = 8). RESULTS: Twenty-eight days after grafting, intimal index
      (intima/media thickness ratio) was 31% lower, neointima/original lumen surface
      ratio was 26% lower, and residual luminal area was 71% greater (4.00 +/- 1.2 mm2
      versus 2.34 +/- 0.9 mm2, all p < 0.01) under verapamil matrices compared with
      control grafts. Neointimal smooth muscle cell content was reduced from 45.4% to
      28.2%, and net neointimal smooth muscle cell thickness was reduced by 47% (30
      microns vs 15.8 microns, both p < 0.01). Verapamil-treated segments distal to the
      matrices also showed significantly lower neointimal smooth muscle cell density
      and increased lumen size. Sensitivity to serotoin and vasomotor responses to
      serotonin, norepinephrine, and sodium nitroprusside in distal segments were
      significantly lower in verapamil-treated grafts than in controls. CONCLUSIONS:
      Periadventitial controlled administration of verapamil below 1% of the systemic
      dose effectively inhibits myointimal hyperplasia in vein grafts. Local polymeric
      drug delivery may be readily applicable to coronary revascularization operations.

PMID- 9240295
TI  - Perinatal induction of immunotolerance to cardiac and pulmonary allografts.
AB  - OBJECTIVES: Tolerance appears to be more easily induced in the fetus before full
      immunocompetence is established, but elucidation of this process is needed. A
      model of perinatal tolerance induction to neonatal skin allografts followed by
      cardiac and pulmonary allografts is described. METHODS: Sixty Lewis (RT11) rat
      fetuses were inoculated intraperitoneally at 18 days gestation with 1 x 10(7) ACI
      (RT1a) rat fetal liver cells (group I); 20 Lewis fetuses were inoculated with 2 x
      10(7) ACI fetal liver cells (Group II). control groups consisted of Lewis fetuses
      inoculated with saline solution (n = 25, group III) and fetuses that were not
      inoculated (n = 25, group IV). Twenty-five of the 50 surviving group I rats
      received ACI skin (< 24 hours old) and heart (8 to 10 weeks old) allografts
      (group IA); the remaining 25 rats received only ACI heart grafts (group IB).
      Groups II, III, and IV received ACI skin and cardiac allografts. Recipients
      tolerant to both skin and cardiac grafts received orthotopic ACI lung grafts and
      third-party skin grafts. Tolerance was indicated by graft survival for more than
      100 days. Limiting dilution and flow cytometric analyses were performed. RESULTS:
      Abortion rates in groups I, II, III, and IV were 17% (10/60), 65% (13/20), 8%
      (2/25), and 4% (1/25), respectively. Specific tolerance to skin, cardiac, and
      lung allografts was observed in seven of 25 group IA recipients (28%) and seven
      of seven group II recipients (100%) compared with no tolerance in any group IB,
      III, or IV recipients (p = 0.03, chi 2 test). A 100-fold reduction of precursor
      cytotoxic T lymphocytes and significant splenocyte and bone marrow chimerism in
      tolerant versus nontolerant rats were noted (p = 0.0001, Student's t test).
      CONCLUSIONS: Using donor-strain fetal liver cells and neonatal skin grafts, we
      achieved higher frequencies of tolerance to solid organ grafts in adulthood with
      lower cell inocula and abortion rates than previously described. Chimerism and
      depressed precursor cytotoxic T lymphocyte frequencies in tolerant recipients
      suggest that hematopoietic stem cell engraftment and clonal deletion/anergy are
      involved in induction of perinatal tolerance.

PMID- 9240296
TI  - An experimental model for the prevention of postanastomotic tracheal stenosis.
AB  - OBJECTIVE: The aim of the current study is to determine the efficiency of an
      external prosthesis made of expanded polytetrafluoroethylene reinforced with a
      continuous silicone spiral to prevent postanastomotic stenosis after surgical
      correction of extensive tracheal defects in rabbits. METHODS: Forty-five rabbits
      were used, divided into three groups of 15 animals each. Group A was the control
      group. Group B animals underwent resection of six-ring segments of the cervical
      trachea and primary anastomosis. The procedure used in group C was similar to
      that used in group B, but the tracheal anastomosis was supported by an external
      expanded polytetrafluoroethylene prosthesis. RESULTS: Direct anastomosis after
      resection of six tracheal rings caused anastomotic stenosis in 100% of the
      animals. We did not observe tracheal stenosis in any rabbit when we applied an
      expanded polytetrafluoroethylene tube as an external stent for the
      tracheotracheal suture. CONCLUSION: We conclude that an external stent can be
      used to prevent tracheal stenosis resulting from the resection of six cervical
      tracheal rings in rabbits.

PMID- 9240297
TI  - Differentiated thyroid carcinoma with airway invasion: indication for tracheal
      resection based on the extent of cancer invasion.
AB  - OBJECTIVE: Although aggressive approaches to locally invasive differentiated
      thyroid carcinoma are reported to improve the prognosis, few investigations have
      provided an indication for airway resection. The present study was undertaken to
      determine the best indication for airway resection for differentiated thyroid
      carcinoma invading the trachea. METHODS: One hundred seventeen patients with
      differentiated thyroid carcinoma invading surrounding structures were
      retrospectively studied for local failures and prognosis and were divided into
      five groups mainly on the basis of macroscopic findings: Group 1 consisted of 40
      patients who underwent tracheal resection for deep tracheal invasion; group 2
      consisted of 14 patients with deep tracheal invasion and no airway resection;
      group 3 consisted of 13 patients with superficial tracheal invasion and no airway
      resection; group 4 comprised 48 patients with extrathyroidal invasion other than
      laryngotracheal structures; and group 5 consisted of two patients who underwent
      tracheal resection for superficial invasion. RESULTS: Resectional management of
      the airway for patients with deep tracheal invasion decreased local recurrence
      and improved postoperative prognosis compared with nonresectional management for
      the tumor, or shaving off tumor from the trachea for patients with superficial
      invasion, did not increase postoperative local failures or mortality (group 3 vs
      groups 4, 5, and 1). CONCLUSION: These results implied that differentiated
      thyroid carcinomas with superficially limited invasion could be treated
      successfully by nonresectional management of the trachea and that those with deep
      invasion should be treated by resection of the invaded trachea.

PMID- 9240298
TI  - Sternal resection for primary or secondary tumors.
AB  - METHODS: From January 1980 to December 1993, 52 patients underwent surgical
      resection for tumors involving the sternum. The series included 20 primary
      malignant tumors, 4 desmoid tumors, 2 malignant tumors infiltrating the sternum
      from adjacent organs, 19 local recurrences or metastases of breast tumors, and 7
      metastases of other tumors. Total sternectomy was performed in 5 patients,
      subtotal sternal resection in 19, and partial resection (less than 50% of the
      sternum) in 28. Concurrent en bloc resection included anterior ribs in 37
      patients, clavicle in 11, lung in 12 patients, pericardium in 7, and diaphragm in
      2. The chest was reconstructed with prosthetic material and a myocutaneous flap
      in 26 patients (50%), prosthetic material only in 12 patients (23%), a
      myocutaneous flap in 5 patients (10%), and other techniques in the remaining
      patients. In 47 patients (90%) the resection was radical, and in the remaining 5
      patients it was palliative. RESULTS: No perioperative deaths occurred. After a
      median follow-up of 39 months, the overall 3-year survival was 58% and the 5-year
      survival 46%, with a median survival of 50 months. In 24 patients with primary
      tumor the 5-year survival after radical resection was 63%, and in 23 patients
      with secondary invasion (direct extension or metastasis) the 5-year survival was
      38% (median 35 months). In recurrent breast cancer the 5-year survival was 48% in
      patients with direct extension to the chest wall and 60% in patients with distant
      bone metastasis. CONCLUSIONS: Our experience demonstrates that sternal resection
      is a safe and effective treatment, which may improve the patient's quality of
      life and achieve a long-term survival not only in primary tumors but also in
      selected secondary malignant tumors of the sternum.

PMID- 9240299
TI  - Continuous antegrade warm blood cardioplegia attenuates augmented coronary
      endothelium-dependent contraction after cardiac global ischemia and reperfusion.
AB  - BACKGROUND: Experiments were designed to evaluate the effect of warm blood
      cardioplegia on endothelium-dependent contraction of the coronary endothelium
      after cardiac global ischemia and reperfusion. METHOD: Dogs (n = 12 in each
      group) were exposed to extracorporeal circulation with the body temperature at 37
      degrees C (group 1) or 28 degrees C (groups 2 and 3). The ascending aorta was
      crossclamped for 120 minutes while continuous infusion of warm blood cardioplegec
      solution (group 1) or intermittent infusion of cold (4 degrees C) crystalloid
      cardioplegic solution (group 2) was performed via the coronary arteries through
      the aortic root. Cardioplegic solution was not used in group 3 animals. The heart
      was then allowed to function for 60 minutes of reperfusion. Reperfused (groups 1,
      2, and 3) and control (group 4) coronary arteries were then harvested for study.
      RESULTS: Perfusate hypoxia caused endothelium-dependent contraction in the
      arteries of all four groups that could be attenuated by NG-monomethyl-L-arginine
      (L-NMMA) or L-NMMA plus D-arginine, but not by L-NMMA plus L-arginine or
      endothelin receptor A and B antagonist PD 145065. The endothelium-dependent
      contraction results in groups 2 and 3 (75% +/- 4% and 80% +/- 5%, respectively)
      were significantly greater than those in groups 1 and 4 (15% +/- 3% and 18% +/-
      5%, respectively). Scanning electron microscope studies showed that platelet
      adhesion and aggregation, areas of microthrombi, disruption of endothelial cells,
      and separation of the intercellular junction could be found in coronary segments
      from groups 2 and 3, but not in vessels from groups 1 and 4. CONCLUSION: These
      experiments suggest that global ischemia and reperfusion enhances hypoxia
      mediated endothelium-dependent contraction of the coronary endothelium and
      damages the ultrastructure. These kinds of changes can be prevented by continuous
      antegrade infusion of warm blood cardioplegic solution during global ischemia.

PMID- 9240300
TI  - Assessment of retrograde cardioplegia with magnetic resonance imaging and
      localized 31P spectroscopy in isolated pig hearts.
AB  - OBJECTIVE: This study was done to determine whether retrograde delivery of
      cardioplegic solution provides uniform blood flow to the myocardium supplied by
      an occluded coronary artery and whether it maintains myocardial energy levels
      beyond the coronary occlusion. METHODS: Isolated pig hearts were used. A
      hydraulic occluder was placed at the origin of the left anterior descending
      coronary artery. The perfusion pressure for retrograde delivery of cardioplegic
      solution was controlled at 40 to 50 mm Hg. Magnetic resonance imaging and
      localized 31P magnetic resonance spectroscopy were used to assess myocardial
      perfusion and energy metabolism, respectively. RESULTS: Magnetic resonance
      perfusion images (n = 7) showed that the perfusion defect that occurred during
      antegrade delivery of cardioplegic solution (as a result of the occlusion of the
      left anterior descending coronary artery) resolved during retrograde delivery of
      cardioplegic solution. Retrograde perfusion delivered similar amounts of flow to
      the jeopardized myocardium as it did to other areas of the myocardium. However,
      the distribution of cardioplegic solution by the retrograde route was
      heterogeneous (cloudlike) across both ventricular walls. 31P magnetic resonance
      spectra showed that the ischemic changes induced by occlusion of the left
      anterior descending artery during antegrade perfusion were greatly alleviated by
      retrograde perfusion; however, it took longer for retrograde cardioplegia (n = 7,
      17.08 minutes) to restore the levels of inorganic phosphate/phosphocreatine
      relative to the effect of releasing the left anterior descending artery occluder
      during antegrade delivery of cardioplegic solution (n = 7, 5.3 minutes).
      CONCLUSIONS: First, retrograde delivery of cardioplegic solution provides
      sufficient flow to the myocardium beyond a coronary occlusion to maintain near
      normal levels of energy metabolites, and second, the efficacy of the retrograde
      route of cardioplegic solution delivery (in terms of distribution of the solution
      and rate of myocardial energy recovery) is significantly lower than that of the
      antegrade route.

PMID- 9240302
TI  - Temperature during cardiopulmonary bypass for coronary artery operations does not
      influence postoperative cognitive function: a prospective, randomized trial.
AB  - OBJECTIVE: The objective was to examine the effect of temperature (28 degrees vs
      36 degrees C) during cardiopulmonary bypass on postoperative cognitive functions
      in a prospective, double-blind, and randomized manner. METHODS: Sixty-two
      patients scheduled for coronary operations were randomized to warm or cold
      cardiopulmonary bypass. Preoperative and postoperative (7 days) neuropsychologic
      evaluations were performed by an observer unaware of cardiopulmonary bypass
      temperature. RESULTS: Fifty-four patients completed the study (cold bypass, n =
      24; warm bypass, n = 30). Significant (p < 0.01) postoperative deterioration for
      tests of psychomotor coordination and verbal memory was noted in both warm and
      cold groups, but no differences were observed between groups. CONCLUSION:
      Temperature during cardiopulmonary bypass for coronary operations does not
      influence postoperative cognitive function.

PMID- 9240303
TI  - Disruption of the aortic arch convexity containing the innominate and left common
      carotid artery origins resulting from blunt trauma.

PMID- 9240304
TI  - Aortic valve replacement in relapsing polychondritis.

PMID- 9240301
TI  - Heparin coating of extracorporeal circuits inhibits contact activation during
      cardiac operations.
AB  - OBJECTIVE: Heparin coating reduces complement activation on the surface of
      extracorporeal circuits. In this study we investigated its effect on activation
      of the contact system in 30 patients undergoing coronary artery bypass grafting
      with the use of a heparin-coated (Duraflo II, Baxter Healthcare Corp., Edwards
      Division, Santa Ana, Calif.; n = 15) or an uncoated extracorporeal circuit (n =
      15). METHODS: Plasma markers that reflect activation of contact (kallikrein-C1
      inhibitor complexes), coagulation (prothrombin fragments F1 + 2), or fibrinolytic
      (plasmin-alpha 2-antiplasmin complexes) systems were determined before and during
      the operation. The generation of kallikrein-C1-inhibitor complexes was reduced by
      62% (p = 0.06) after the onset of cardiopulmonary bypass and by 43% (p = 0.026)
      after the cessation of bypass in the group in which a heparin-coated circuit was
      used compared with the group in which the circuit was uncoated. Generation was
      reduced by 58% (p = 0.06) when the ratio of kallikrein-C1-inhibitor to
      prekallikrein after onset of bypass was considered. We detected significant
      increases in F1 + 2 levels in both groups and increases in plasmin-alpha 2
      antiplasmin complexes in the heparin-coated group at cessation of bypass, but no
      intergroup differences were observed. Thus use of heparin-coated extracorporeal
      circuits during cardiac operations reduces formation of kallikrein-C1-inhibitor
      complexes when compared with use of uncoated circuits. The heparin coating is not
      accompanied by similar reductions in coagulation or fibrinolysis, suggesting that
      thrombin and plasmin formation during cardiopulmonary bypass occurs mainly
      independently of the contact system activation.

PMID- 9240305
TI  - Pericardial patch augmentation of restrictive innominate vein and division of
      left superior vena cava in unroofed coronary sinus syndrome.

PMID- 9240306
TI  - Repair of truncus arteriosus with intact ventricular septum (Van Praagh type B2)
      in a neonate.

PMID- 9240307
TI  - Ultrafast computed tomography in infectious pseudoaneurysm of the left
      ventricular outflow tract.

PMID- 9240308
TI  - Combined suppressive effect of cardiopulmonary bypass and aging on cell-mediated
      immunity.

PMID- 9240309
TI  - Aortic root endoscopy in valve-sparing operations.

PMID- 9240310
TI  - Diagnosis and successful treatment of a unique form of malfunction of the
      heartmate left ventricular assist device.

PMID- 9240311
TI  - Impregnation of sewing ring with antibiotics to avoid prosthetic valve
      endocarditis.

PMID- 9240312
TI  - Measurement of aortic diameter.

PMID- 9240313
TI  - Neuropsychologic outcome after normothermic cardiopulmonary bypass.

PMID- 9240314
TI  - Early outcome assessment for 2228 consecutive carotid endarterectomy procedures:
      the Cleveland Clinic experience from 1989 to 1995.
AB  - PURPOSE: Several randomized trials now have established guidelines regarding
      patient selection for carotid endarterectomy (CEA) that have been widely accepted
      but have little relevance unless they are considered in the context of
      perioperative risk. The purpose of this study was to demonstrate the feasibility
      of early outcome assessment using a computerized database. METHODS: Since 1989
      demographic information and in-hospital results for all surgical procedures
      performed by the members of our department have been entered into a prospective
      registry. For the purpose of this report, we have analyzed the stroke and
      mortality rates for 2228 consecutive CEAs (2046 patients), including 1924 that
      were performed as isolated operations and 304 that were combined with
      simultaneous coronary artery bypass grafting (CABG). This series incidentally
      contains a total of 153 reoperations for recurrent carotid stenosis. RESULTS: The
      respective stroke and mortality rates were 0.5% and 1.8% for all isolated CEAs,
      4.3% and 5.3% for all CEA-CABG procedures, and 4.6% and 2.0% for carotid
      reoperations. According to a multivariable statistical model, the composite
      stroke and mortality rate for isolated CEA was significantly influenced by female
      gender (p = 0.050), by the urgency of intervention (p = 0.026), and by carotid
      reoperations (p = 0.024). Gender (p = 0.030) and urgency (p = 0.040) also were
      associated with differences in the stroke rate alone; furthermore, the incidence
      of perioperative stroke was higher in conjunction with synthetic patching (odds
      ratio, 2.6; 95% confidence interval, 1.2 to 5.3) and was marginally higher with
      primary arteriotomy closure (odds ratio, 2.7; 95% confidence interval, 0.8 to
      9.5) compared with vein patch angioplasty (1.3%). The method used to repair the
      arteriotomy was the only independent factor that qualified for the multivariable
      composite stroke and mortality models that were applied to the combined CEA-CABG
      procedures, but too few patients in this cohort had synthetic patches or primary
      closure to validate the perceived superiority of vein patching. CONCLUSIONS:
      Prospective outcome assessment is essential to reconcile the indications for CEA
      with its actual results, and it may lead incidentally to important observations
      concerning patient care.

PMID- 9240315
TI  - In situ repair of aortobronchial, aortoesophageal, and aortoenteric fistulae with
      cryopreserved aortic homografts.
AB  - PURPOSE: The surgical treatment of fistulae that originate from aortic aneurysms
      or prosthetic aortic grafts carries a high mortality rate. We investigated
      whether in situ repair with cryopreserved aortic homografts would improve the
      outcome. METHODS: Between April 1994 and June 1996, 11 patients (mean age, 62 +/-
      10 years) with aortobronchial, aortoesophageal, or aortointestinal fistulae
      originating from mycotic aneurysms (five of 12) or prosthetic aortic grafts (six
      of 12) underwent in situ replacement of the thoracic (seven of 10) or abdominal
      (four of 10) aorta with homografts. Emergency surgery was performed in eight of
      11 patients (73%). RESULTS: The hospital mortality rate was 9%; there was one
      sudden cardiac death on the seventh postoperative day. The mean hospital stay was
      42 +/- 26 days (range, 21 to 90 days). After surgery, antibiotics were given for
      38 +/- 6 days (range, 28 to 42 days). Neither reinfection, suture line rupture,
      nor anastomotic aneurysms were observed by magnetic resonance angiography,
      computed tomography, angiography, or transesophageal echocardiography after 14.3
      +/- 8.2 months (range, 6 to 31 months). In one patient, percutaneous vascular
      stent placement was necessary after 18 months for an anastomotic stenosis of a
      thoracic homograft. CONCLUSIONS: In situ repair with cryopreserved aortic
      homografts seems to be a promising step in the treatment of aortobronchial,
      aortoesophageal, and aortointestinal fistulae. This technique has a low operative
      mortality rate and may prevent reinfection.

PMID- 9240316
TI  - Treatment of iatrogenic femoral artery pseudoaneurysm with percutaneous thrombin
      injection.
AB  - PURPOSE: Local compression has been advocated for the treatment of femoral artery
      pseudoaneurysms. Although it is effective and has a high success rate, this
      method bears some limitations; among them are prolonged procedure time,
      discomfort for patients, and recurrence. As a potent thrombosis-inducing agent,
      thrombin has been used topically, and occasionally intravascularly, for
      hemostasis. Pseudoaneurysms with a narrow connecting tract to the native artery
      may be suitable for treatment with thrombin injection to induce intracavitary
      coagulation. METHODS: Patients with pseudoaneurysms of the femoral artery were
      evaluated by ultrasonography. Under ultrasound guidance, an intravenous catheter
      was introduced percutaneously into the pseudoaneurysm, with the catheter position
      confirmed by contrast ultrasonography. One thousand units of thrombin dissolved
      in normal saline solution was then injected slowly into the pseudoaneurysm
      through the catheter to induce thrombosis. The patients were monitored closely
      for any adverse effects after thrombin injection. RESULTS: A total of five
      patients with femoral artery pseudoaneurysms were treated with direct
      percutaneous thrombin injection under ultrasound guidance. Within seconds of
      thrombin injection thrombus formation was evident, and blood flow in the
      pseudoaneurysm soon ceased when the thrombosis extended to the connecting tract.
      All procedures were uneventful and successful. No recurrence was noted during
      follow-up periods of 1 to 28 months. CONCLUSION: Our initial experience with the
      small number of patients demonstrates the simplicity, lack of morbidity, and high
      success rate for ultrasound-guided percutaneous thrombin injection for the
      treatment of femoral artery pseudoaneurysms.

PMID- 9240317
TI  - Arterial and venous repair with vascular clips: comparison with suture closure.
AB  - PURPOSE: Nonpenetrating, arcuate-legged titanium vascular closure staple (VCS)
      clips were initially developed for microvascular anastomoses with little
      experience of their use in larger vessels. The purpose of this study was to
      compare the VCS clips with standard suture closure of arteriotomies and
      venotomies in common iliac vessels of pigs. METHODS: In nine pigs, longitudinal 1
      cm iliac arterial and venous incisions were repaired with VCS clips on one side
      and continuous 6-0 polypropylene suture on the other, and the macroscopic and
      microscopic results were assessed after 3 months. RESULTS: The time required for
      vessel repair was significantly shorter with clips than with sutures both in
      arteries (51 +/- 9 vs 414 +/- 36 seconds) and in veins (100 +/- 32 vs 439 +/- 45
      seconds). There was no significant difference in the inner diameter, intimal
      thickness, or intima-to-media height ratios of the arteries or veins after either
      method of closure. CONCLUSIONS: Repair of 1 cm incisions in small-diameter
      arteries and veins with VCS clips results in wound healing as good as that
      achieved with standard suture closure, when assessed for patency, leakage, degree
      of narrowing, and intimal reaction. The time required for clip closure is
      considerably shorter than for suture closure.

PMID- 9240318
TI  - Detection of Chlamydia pneumoniae in atherosclerotic plaques in the walls of
      arteries of lower extremities from patients undergoing bypass operation for
      arterial obstruction.
AB  - PURPOSE: To study surgically excised vascular tissue from lower extremities for
      the presence of Chlamydia pneumoniae, to extend the previously described
      association of the organism with atherosclerosis. METHODS: Arterial biopsy
      specimens obtained from femoral and popliteal arteries during bypass operation
      for claudication were examined by immunocytochemical analysis and polymerase
      chain reaction for the presence of organisms. RESULTS: C. pneumoniae was detected
      in atherosclerotic plaques by either method in either artery of 11 of 23 patients
      (48%). Eight of 21 popliteal and three of 18 femoral arteries had positive
      results. CONCLUSIONS: Detection of C. pneumoniae in peripheral arteries indicates
      that the organism is widespread in atherosclerosis of the vascular system.

PMID- 9240319
TI  - Immunosuppression for human saphenous vein allograft bypass surgery: a
      prospective randomized trial.
AB  - PURPOSE: Vein allografts are an alternative bypass conduit for patients who lack
      adequate autogenous vein. Animal studies have demonstrated that patency can be
      augmented by low-dose immunosuppression with azathioprine. METHODS: In a
      prospective trial, 40 patients (20 men, 20 women) were randomly assigned to
      receive (17) or to not receive (23) azathioprine (1 mg/kg/day) after
      cryopreserved vein allograft bypass grafting. Patients had pain or tissue loss
      that required bypass grafting to pedal or crural outflow and lacked adequate
      autogenous saphenous vein. Anti-HLA antibody screens were obtained before and
      after surgery. Biopsies of allografts were performed at implantation and at all
      subsequent opportunities. Postoperative physical and vascular laboratory
      examinations occurred every 3 months. RESULTS: During the 31-months follow-up
      interval (mean, 15.7 months) there were 10 deaths (none immunosuppression
      related). The primary graft patency rate at 12 months was 13%, and the limb
      salvage rate was 42%. No significant difference (p > 0.05) was noted between
      immunosuppressed and control groups for mortality rate, primary graft patency
      rate, or limb salvage rate. As a predictor of graft failure, positive
      preoperative anti-HLA antibody screen (8 patients) approached significance (p =
      0.09). Of 22 explanted grafts, 13 (59%) had histologic evidence of rejection (six
      immunosuppressed, seven control). Seven patients who had negative results of
      preoperative anti-HLA antibody screens converted after surgery, and six patients
      had positive results of preoperative screens that became more strongly positive.
      CONCLUSION: Vein allograft failure is in part mediated by rejection, which is not
      eliminated by low-dose azathioprine. Both humoral (antibody) and cellular
      responses to vein allografts develop. The poor patency rates of vein allograft
      bypass grafts may be improved by more potent immunosuppression as well as
      improvement in allograft procurement, preservation, and matching.

PMID- 9240320
TI  - Duplex imaging findings predict stenosis after carotid endarterectomy.
AB  - PURPOSE: This study was performed to determine whether early duplex findings
      predicted restenosis after carotid endarterectomy. METHODS: One hundred ninety
      two symptomatic patients who underwent carotid endarterectomy were studied with
      color duplex imaging at 1 day and 1 week after surgery to identify minor residual
      disease (causing < 50% stenosis), arterial kinking, and suture stricture, and to
      measure the external and luminal diameters of the carotid bulb and distal
      internal carotid artery. Patients were then observed prospectively with duplex
      surveillance for a median of 24 months to identify > 50% restenosis. RESULTS:
      Twenty-five stenoses > 50% of the operated carotid artery (13%) were identified,
      four at 1 day (residual) and 21 at a median follow-up of 6 months (restenosis).
      On multiple logistic regression analysis, > 50% restenosis was found to be
      associated with minor day-1 residual stenosis (p = 0.01) and with small luminal
      diameter of the distal internal carotid artery (p = 0.03) as measured 1 week
      after carotid endarterectomy. Life table analysis showed restenosis at 24 months
      to be more common for patients with below-median than patients with above-median
      carotid bulb external diameter (18% vs 5%, respectively; p = 0.01). CONCLUSIONS:
      Duplex scanning within a week of carotid endarterectomy identifies > 50% residual
      stenosis, in addition to minor residual 25% to 50% stenosis and small carotid
      dimensions, which are good predictors of > 50% restenosis at 6 months.

PMID- 9240321
TI  - Validation of duplex ultrasonography in detecting competent and incompetent
      perforating veins in patients with venous ulceration of the lower leg.
AB  - PURPOSE: Incompetent perforating veins play an important role in the etiologic
      mechanism of venous ulceration and recurrent varicose veins. The anatomic and
      functional status of the venous system can be evaluated by duplex
      ultrasonography. To determine the value of this technique in the identification
      of competent and incompetent perforating veins, a prospective study was
      performed. METHODS: In patients who underwent subfascial exploration for venous
      ulceration of the lower leg, the preoperative findings of duplex ultrasonography
      were compared with the findings at surgical exploration. RESULTS: In 20
      consecutive patients, 42 incompetent and 8 competent perforating veins were
      detected by duplex ultrasonography. During operation the location of all 50
      perforating veins appeared to be predicted correctly. Eleven additional
      perforating veins that had not been detected by duplex ultrasonography were found
      during operation. The sensitivity and specificity of duplex ultrasonography in
      predicting the site of perforating veins at the medial side of the lower leg in
      our study were 79.2% and 100%, respectively, for incompetent perforating veins
      and 82% and 100%, respectively, for competent and incompetent perforating veins.
      CONCLUSION: These figures indicate that duplex-guided local exploration of the
      lower leg in patients with venous ulceration as a result of incompetent
      perforating veins would miss a substantial number of perforating veins, possibly
      leading to incomplete healing or recurrent ulceration.

PMID- 9240322
TI  - A new method for the assessment of venous insufficiency in primary varicose veins
      using near-infrared spectroscopy.
AB  - PURPOSE: Patients with chronic venous insufficiency (CVI) were evaluated from the
      aspect of ambulatory venous function using near-infrared spectroscopy (NIRS).
      METHODS: Seventy-two primary varicose veins of 59 patients (varicose group) and
      20 normal limbs of 13 volunteers (normal group) were studied. The affected limbs
      of the patients were divided into three groups according to the classification
      advocated by an International Consensus Committee in 1995: mild CVI with class 2
      or 3 (50 limbs); moderate CVI with class 4 (11 limbs); and severe CVI with class
      5 or 6 (11 limbs). All of the patients underwent a treadmill walking test, during
      which NIRS was applied. Oxygenated hemoglobin (OxyHb) and deoxygenated hemoglobin
      (DeoHb) were continuously measured by NIRS during exercise. The ambulatory venous
      retention index (AVRI) obtained from serial changes in DeoHb was assessed
      comparatively in the four groups (normal and mild to severe CVI). In addition, 19
      limbs in 13 patients were evaluated with air plethysmography for comparison with
      the data obtained by NIRS. RESULTS: Two distinct patterns of DeoHb change were
      observed. During exercise, the DeoHb level decreased in the normal group as a
      result of calf muscle contraction, whereas in the varicose group the DeoHb level
      rose because of an apparent venous reflux into the calf muscles. AVRI studies
      demonstrated a significant difference (p < 0.0001) among groups. Although there
      was no apparent relationship between AVRI and ejection fraction, AVRI showed a
      significant correlation with the venous filling index (r = 0.61) and a weak
      correlation with the residual volume fraction (r = 0.41). CONCLUSION: NIRS is
      useful for accurately assessing ambulatory venous dysfunction in patients with
      primary varicose veins.

PMID- 9240324
TI  - Platelet-derived growth factor production by cells from Dacron grafts implanted
      in a canine model.
AB  - PURPOSE: Previous studies of grafts implanted in dogs documented a time-dependent
      increase in platelet-derived growth factor (PDGF) production that correlated with
      inner-capsule thickness. The purpose of this study was to identify the cells in
      vascular grafts that produce PDGF. METHODS: Dacron thoracoabdominal grafts were
      seeded with autologous endothelial cells (ECs), implanted in 11 beagles, and
      removed after 4 or 20 weeks. ECs and smooth muscle cells (SMCs) were cultured
      from grafts and adjacent aorta, and PDGF in the conditioned media was measured by
      radioreceptor assay. The PDGF A-chain mRNA level in freshly harvested cells was
      assessed using reverse transcriptase, followed by polymerase chain reaction, and
      expressed as a ratio of glyceraldehyde-3-phosphate dehydrogenase signal.
      Localization of PDGF A-chain and B-chain protein was also examined with
      immunohistochemical analysis. RESULTS: Graft and aortic ECs in primary culture
      did not produce significantly different amounts of PDGF in 72 hours, averaging
      368 +/- 160 and 340 +/- 81 pg/microgram DNA, respectively. Graft SMCs in primary
      culture produced significantly more PDGF than aortic SMCs (584 +/- 343 and 113 +/
      94 pg/microgram DNA, respectively; p < 0.01). Graft SMC PDGF secretion remained
      greater than aortic SMC PDGF secretion through at least six cell passages. PDGF A
      chain mRNA levels were not significantly different for aortic or graft ECs. The
      PDGF A-chain mRNA level was significantly higher for graft SMCs than aortic SMCs
      (2.44 +/- 0.67 and 1.45 +/- 0.57 pg/microgram, respectively; p < 0.03).
      Immunocytochemical analysis detected PDGF A-chain and B-chain protein in the ECs
      from both native aorta and graft as well as the subendothelial SMCs in the graft,
      but not in the SMCs of the native aorta. CONCLUSIONS: These results suggest that
      graft SMCs are functionally altered, producing more PDGF than aortic SMCs. PDGF
      produced by graft SMCs may contribute to the development of intimal hyperplasia.

PMID- 9240323
TI  - Characterization of endothelin receptors in human varicose veins.
AB  - PURPOSE: Experiments were designed to characterize endothelin receptors in human
      varicose veins. Three groups of veins were studied: (1) varicose vein (VV)
      tributaries of the greater saphenous vein from patients who were undergoing vein
      stripping for primary varicosity; (2) greater saphenous veins (SVs) from the same
      patients; and (3) greater saphenous veins from patients without varicosity who
      were undergoing arterial reconstruction (control). METHODS: Veins were either cut
      into rings and suspended in organ chambers for measurement of isometric force,
      prepared for receptor binding of membrane proteins, or were prepared for
      measurement of preproendothelin mRNA by reverse transcriptase-polymerase chain
      reaction (RT-PCR). RESULTS: Endothelin-1 (10(-11) to 10(-7) mol/L) produced
      similar concentration-dependent contractions in rings with or without
      endothelium. Maximal tensions were significantly greater in control veins
      compared with either SVs or VVs. Sarafotoxin S6c (10(-11) to 3 x 10(-7) mol/L),
      which is selective for the endothelin-B receptor, also produced concentration
      dependent increases in tension in all veins. Sarafotoxin S6c responses in VVs
      were shifted significantly rightward compared with either SVs or control. Maximal
      tensions to sarafotoxin S6c also were significantly greater in control veins
      compared with either SVs or VVs. In receptor binding studies, the number of
      binding sites as defined by competitive inhibition of 125I-endothelin-1 by
      endothelin-1 was less in VVs than control veins. Competitive inhibition of 125I
      endothelin-1 with endothelin-3 (both A and B receptors) or sarafotoxin S6c (B
      receptors only) suggests that the difference in receptor number between varicose
      and nonvaricose veins is attributable to differences in the endothelin-B receptor
      subtype. Binding affinities were not significantly different for either of the
      receptor subtypes in all veins studied. Preproendothelin mRNA as quantitated by
      RT-PCR tended to be higher in VVs compared with either SVs or control veins.
      CONCLUSIONS: Decreased contractions to endothelin-1 in both varicose and
      saphenous veins of patients with primary varicosity may be associated with a
      decrease in the number of receptors. These receptors may be downregulated in
      response to increased production of endothelin-1, which is regulated at the
      transcriptional level.

PMID- 9240325
TI  - Vascular endothelial growth factor expression in canine peripheral vein bypass
      grafts.
AB  - PURPOSE: Autologous veins used as arterial bypass grafts undergo initial loss of
      the endothelial cell (EC) lining, which is followed by reendothelialization. We
      characterized the expression of the EC-specific angiogenic mitogen, vascular
      endothelial growth factor (VEGF), in vascular grafts to help elucidate the
      molecular and cellular events after bypass procedures. METHODS: Cephalic vein
      femoral artery interposition grafts were placed in mongrel dogs. Vein grafts and
      arteries were harvested at either 48 hours or 4 weeks after bypass, the total RNA
      was isolated, and the VEGF mRNA expression was evaluated by Northern blot
      analysis. Tissue segments from each time period were evaluated by
      immunohistochemical analysis using anti-VEGF antibodies. RESULTS: VEGF mRNA
      expression in vein grafts as compared with control veins was increased 2.5-fold
      48 hours after bypass grafting (p = 0.02) but returned to initial control levels
      in grafts removed at 4 weeks. Distal arterial segments, which included the
      anastomotic site without attached vein graft, had a 21.4-fold increase in VEGF
      expression at 48 hours (p = 0.02) and a 6.6-fold increase at 4 weeks (p < 0.01)
      as compared with control arterial segments. Vessels subjected to arteriotomy or
      ischemia alone also demonstrated increased VEGF expression. Immunohistochemical
      analysis revealed VEGF protein within ECs and smooth muscle cells of the venous
      bypass graft, with maximal levels observed within intimal hyperplasia at the
      arterial anastomosis. CONCLUSIONS: After arterial reconstruction procedures using
      venous conduits, VEGF is significantly increased at 48 hours in the vein graft
      and arterial anastomosis. VEGF expression in the vein graft normalizes within 4
      weeks but remains significantly elevated in the adjacent arterial segment.
      Increased VEGF production after arterial grafting may facilitate
      reendothelialization, thus partially accounting for optimal patency rates
      achieved with autologous vein grafts.

PMID- 9240326
TI  - Anti-VLA-4 antibody reduces intimal hyperplasia in the endarterectomized carotid
      artery in nonhuman primates.
AB  - PURPOSE: Recently, very late antigen-4 (VLA-4) has been shown to mediate initial
      monocyte adhesion and migration to the injured artery. We hypothesized that
      blocking monocyte adhesion using a specific monoclonal antibody against VLA-4 may
      reduce intimal hyperplasia. METHODS: Bilateral carotid endarterectomies were
      performed in eight adult baboons. Among them, five animals received an
      intravenous bolus injection of anti-VLA-4 antibody (3 mg/kg) during surgery and
      again after 2 weeks. Three animals underwent bilateral carotid endarterectomies
      and served as untreated control subjects. Specimens were harvested at 4 weeks and
      subjected to morphometric analysis, cell proliferation assay, and immunostaining
      for macrophages. RESULTS: All of the endarterectomized arteries were patent
      except for one in the treated group. The number of macrophages in the intimal
      tissues was significantly reduced in the treated arteries compared with that in
      the control vessels (15.78 +/- 3.05 cells/section versus 33.50 +/- 6.13
      cells/section; p < 0.001). The cell proliferation rate was significantly lower (p
      < 0.001) in the treated vessels (2.88% +/- 1.07%) compared with the control
      vessels (4.89% +/- 0.77%). The intimal area at the endarterectomized sites of
      carotid arteries was significantly less (p < 0.05) in the group treated with the
      anti-VLA-4 antibody (1.10 +/- 0.68 mm2) than in the control group (2.00 +/- 0.52
      mm2). CONCLUSION: These data show that blocking monocyte adhesion by use of an
      anti-VLA-4 antibody significantly reduces the number of intimal macrophages,
      intimal cell proliferation, and intimal hyperplasia in injured carotid arteries
      in baboons. This study supports a central role for macrophages in the development
      of intimal hyperplasia and may suggest a new therapeutic strategy to prevent
      clinical restenosis.

PMID- 9240327
TI  - An ultrastructural study of progressive intimal hyperplasia in rat vein grafts.
AB  - PURPOSE: Intimal hyperplasia (IH) poses the greatest challenge for vein graft
      success. This fibroproliferative disorder causes obliterative stenosis and
      frequent graft occlusion. Although its causes remain poorly understood, it has
      been proposed that IH begins as a wound-healing response that cascades into a
      chronic state of unchecked proliferation. In this ultrastructural study, IH
      development and concomitant cell changes were evaluated in rat vein grafts.
      METHODS: Epigastric vein-to-femoral artery grafts were placed in Lewis rats using
      standard microsurgical techniques. At various time points, grafts were harvested
      and processed for transmission electron microscopic, histologic, and
      immunohistochemical analyses. The proximal region, which displayed the most
      marked IH, was assessed for ultrastructural changes. RESULTS: Our findings
      showed: (1) regeneration of the damaged endothelium by cells displaying an
      activated appearance; (2) early and complete smooth muscle cell death, with
      subsequent replacement by myofibroblastic cells; (3) extensive and sustained
      graft infiltration by monocytes/macrophages; and (4) intramural fibrin
      deposition. CONCLUSIONS: The rat vein graft wall was substantially altered after
      implantation into the arterial circulation. During and after IH development, the
      cells in the graft did not resemble cells that are present in the nongrafted
      epigastric vein. Marked cell death, mononuclear cell infiltration, and the
      presence of myofibroblastic cells suggest a state of aberrant wound healing.

PMID- 9240328
TI  - Platelet-derived growth factor and extracellular matrix proteins provide a
      synergistic stimulus for human vascular smooth muscle cell migration.
AB  - PURPOSE: Smooth muscle cell (SMC) migration contributes significantly to the
      hyperplastic response that follows arterial injury. In vitro studies have shown
      that a number of growth factors and extracellular matrix (ECM) proteins
      individually stimulate vascular SMC migration. However, after arterial injury,
      SMCs exist in a complex environment in which they are exposed to many of these
      proteins simultaneously. The response of SMCs to multiple simultaneous stimuli
      may differ significantly from their response to any single individual stimulus.
      In this study, we evaluated the chemotactic response of human vascular SMCs to
      various combinations of growth factors and ECM proteins. METHODS: Human saphenous
      vein SMCs were used for all experiments. Using a 4-hour modified Boyden-chamber
      assay, we evaluated the effect on SMC chemotaxis of combinations of one of three
      growth factors (platelet-derived growth factor [PDGF]-AB, basic fibroblast growth
      factor [bFGF], or epidermal growth factor [EGF]), and one of four ECM proteins
      (fibronectin, laminin, or collagen type I or IV). A standard fluorimetric assay
      was used to assess changes in intracellular calcium ([Ca2+]i) in response to the
      various combinations of growth factors and ECM proteins. RESULTS: A simple
      additive effect was seen between ECM proteins and bFGF or EGF. However, when SMCs
      were simultaneously exposed to PDGF and ECM proteins, we observed a synergistic
      increase in chemotaxis. This synergy was evident for all concentrations of
      collagen type I and IV but only with higher concentrations of fibronectin and
      laminin. We evaluated whether intracellular calcium may be the signaling pathway
      through which this synergistic effect is mediated. Although ECM proteins alone
      did not stimulate a rise in [Ca2+]i, ECM proteins enhanced the early peak in
      [Ca2+]i induced by PDGF. CONCLUSION: These data show that PDGF acts
      synergistically with the ECM proteins to promote SMC migration; this effect
      appears to be specific for PDGF and was not observed with other growth factors.
      The mechanism responsible for this phenomenon may be a synergistic increase in
      [Ca2+]i in SMCs simultaneously exposed to both proteins.

PMID- 9240329
TI  - Exogenously administered interleukin-10 decreases pulmonary neutrophil
      infiltration in a tumor necrosis factor-dependent murine model of acute visceral
      ischemia.
AB  - INTRODUCTION: Visceral ischemia and reperfusion associated with thoracoabdominal
      aortic aneurysm (TAAA) repair results in lung injury, which appears to be
      mediated in part by proinflammatory cytokines. The purpose of this study was to
      determine the effect of exogenous administration of the antiinflammatory
      cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine
      production (IL-6 and TNF alpha) and pulmonary neutrophil infiltration after acute
      visceral ischemia-reperfusion. METHODS: Two hours before 25 minutes of
      supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an
      intraperitoneal injection of rhIL-10 (0.2 microgram [n = 20], 2 micrograms [n =
      20], 5 micrograms [n = 25], or 20 micrograms [n = 15]), and 16 mice received
      murine anti-IL-10 IgM 200 micrograms. Twenty-five additional mice underwent
      visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent
      laparotomy without aortic occlusion (sham). RESULTS: Pretreatment with exogenous
      rhIL-10 resulted in significant reductions in lung neutrophil infiltration with
      0.2 microgram, 2 micrograms, and 5 micrograms per mouse of rhIL-10 compared with
      lung neutrophil levels in control mice that underwent acute visceral ischemia
      reperfusion alone (p < 0.05). In addition, serum TNF alpha was detected in 50% of
      control mice and in 75% of mice that received murine anti-IL-10, but in none of
      the mice that received rhIL-10 (2 micrograms per mouse) or the mice that
      underwent sham operative procedures (p < 0.05 by chi 2 analysis). CONCLUSION:
      Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNF
      alpha in this model of visceral ischemia-reperfusion injury. Thus the use of
      exogenous IL-10 may offer a novel therapeutic approach to decrease the
      complications that are associated with TAAA repair.

PMID- 9240330
TI  - Improved retroviral transduction efficiency of vascular cells in vitro and in
      vivo during clinically relevant incubation periods using centrifugation to
      increase viral titers.
AB  - Vascular cells are an important target for gene transfer because of their
      potential to deliver gene products both locally and systemically. Direct
      retroviral gene transfer to vascular cells in vivo has been limited by
      inefficient rates of transduction. We hypothesized that vascular cell
      transduction efficiency (TE), during short retroviral incubation periods, is
      significantly improved in vitro and in vivo using centrifugation to increase
      viral titer. Furthermore, we hypothesized a linear relationship between
      concentration of viable viral particles (measured as colony-forming units
      (CFUs)/cell) and retroviral TE during short incubation periods. Cultured rat
      pulmonary artery endothelial cells (RPAECs), rat aortic smooth muscle cells
      (RSMCs), and human iliac artery endothelial cells (HIAECs) demonstrated a strong
      correlation between TE and high concentrations of virus (> 100 CFU/cell) during
      retroviral incubation periods of 10 to 60 minutes. High titers, and thereby high
      concentrations, were achieved by centrifugation and resuspension in a fraction of
      the original volume. Titers was consistently increased tenfold, for a twentyfold
      increase in concentration by volume. A 20-minute incubation with a Moloney murine
      leukemia-derived retroviral vector coding for human placental alkaline
      phosphatase, pLJhpAP, at a concentration of 1150 CFU/cell yielded TEs of 10.6% +/
      0.7%, 40.4% +/- 1.6%, and 15.1% +/- 2.0% for RPAECs, RSMCs, and HIAECs,
      respectively. A similar effect was shown using the Moloney murine leukemia
      derived MFGlacZ retroviral vector, coding for Escherichia coli beta
      galactosidase. Increased titer and concentration had no effect on target cell
      viability, as shown by trypan blue exclusion. Although RSMCs had the most cells
      transduced in a given incubation period (p < 0.05), RPAECs had the highest
      replication rate (p < 0.05), suggesting the importance of factors other than cell
      cycle on retroviral TEs during short, clinically relevant incubation periods. In
      subsequent in vivo experiments, gene transfer was achieved in the rat carotid
      artery during a 20-minute incubation period infusing the concentrated pLJhpAP
      retrovirus after carotid balloon injury. Rats infused with virus 2 days after
      balloon injury exhibited hpAP activity (0 to 10 cells/section/rat) in the
      neointima of five out of six rats. Rats infused 4 days after balloon injury
      exhibited hpAP activity (0 to 25 cells/section/rat) in the media and adventitia
      of five out of five rats. Control rats that received the balloon injury alone or
      the balloon injury and unconcentrated retrovirus exhibited zero hpAP activity. We
      conclude that the TE of retroviral-mediated gene transfer to vascular cells in
      vitro and in vivo can be improved during short, clinically relevant incubation
      periods using centrifugation to increase retroviral titer, and thereby
      concentration of viable viral particles.

PMID- 9240332
TI  - Regression of an abdominal aortic aneurysm after endograft exclusion.
AB  - We describe the regression of a 6.5 cm diameter abdominal aortic aneurysm in a 71
      year-old patient within 1 year of aortic endograft placement. The aneurysm
      decreased in size to 4 cm at 3 months and was 3.3 cm at 8 months on duplex
      examination. By 1 year a spiral computed tomographic study confirmed complete
      regression of the aneurysm, with mild shortening and angulation of the
      unsupported body of the aortoiliac endoluminal prosthesis. The case demonstrates
      a potential of endograft treatment of aortic aneurysms and decribes the changes
      in prosthesis configuration and position that occurred after implantation.

PMID- 9240331
TI  - Laparoscopic aortobifemoral bypass.
AB  - PURPOSE: To determine the potential benefits of applying laparoscopic techniques
      for the intraabdominal insertion of aortofemoral grafts and to compare results
      with those of conventional surgery. METHODS: Having previously demonstrated the
      feasibility of a totally laparoscopic aortofemoral bypass technique using carbon
      dioxide peritoneal insufflation in a porcine model, we now report our first human
      experience with this laparoscopic technique in a 49-year-old man. RESULTS: The
      patient's postoperative course was marked by his minimal requirements for
      analgesia, early ambulation, and discharge from the hospital in the morning of
      the third postoperative day. CONCLUSIONS: The benefits of a laparoscopic approach
      to aortobifemoral bypass grafting in terms of financial savings and earlier
      rehabilitation in this patient was significant. This less-invasive procedure
      warrants further investigation.

PMID- 9240333
TI  - Aortic corset syndrome.
AB  - The majority of proximal anastomotic complications of aortofemoral bypass grafts
      are related to the formation of pseudoaneurysms or true proximal aneurysmal
      dilation of the residual infrarenal aorta. The late development of occlusive
      disease at the proximal anastomosis is an extremely rare event. We report two
      patients in whom symptomatic stenoses developed involving the proximal
      anastomoses of aortofemoral bypass grafts originally placed for aortoiliac
      occlusive disease. Surgical exploration demonstrated the presence of a
      constricting prosthetic corset wrapped around the proximal suture line of each
      graft. Exuberant neointimal hyperplasia was responsible for both stenoses.

PMID- 9240334
TI  - Aortic diverticulum without vascular ring: a rare cause of dysphagia.
AB  - In an adult with severe dysphagia, diagnosis of aneurysmal aberrant subclavian
      artery was suspected on computed tomogram; no vascular ring was visible on
      arteriogram. A diverticulum of the aortic isthmus was surgically resected.
      Histologic analysis ruled out acquired disease. In conclusion, dysphagia related
      to esophageal compression may be caused by an isolated congenital aortic
      diverticulum.

PMID- 9240335
TI  - Secondary aortoesophageal fistula.
AB  - Secondary aortoesophageal fistula is the rarest type of aortopeptic fistula,
      characterized by communication between the reconstructed aorta and the esophagus.
      This condition has been reported to be uniformly fatal, even after prompt
      diagnosis and treatment. We report what may be the first case of a successfully
      managed secondary aortoesophageal fistula that occurred 14 months after repair of
      a Crawford type II thoracoabdominal aortic aneurysm. The entity was diagnosed
      with a combination of esophagogastroduodenoscopy and aortography. At exploration,
      a communication between the proximal anastomosis and the esophagus with otherwise
      minimal mediastinal contamination was encountered. The anastomosis was replaced
      with an interposition polytetrafluoroethylene graft, and the esophageal defect
      was debrided, primarily closed, and reinforced with adjacent old aneurysm wall.
      There were no postoperative complications, and the patient remains well 18 months
      after fistula repair.

PMID- 9240336
TI  - Floating thrombus in the ascending aorta: a rare cause of peripheral emboli.
AB  - The ascending aorta may be the site of origin of systemic embolization in some
      cases that do not have an identifiable source. We report a case in which a free
      floating thrombus in the noncoronary sinus of Valsalva was detected by
      transesophageal echocardiography as a source of left axillary artery embolism.
      After removal of this pedunculated thrombus of unknown cause, which was attached
      on a macroscopically and histologically normal aortic wall, the patient made an
      uneventful recovery.

PMID- 9240337
TI  - A unique approach in the management of vena caval thrombosis in a patient with
      Klippel-Trenaunay syndrome.
AB  - Vena caval thrombosis has posed a surgical therapeutic challenge for many years.
      Historically, spiral vein grafts and synthetic materials used as prostheses have
      had variable results. The use of the stent may serve as a more promising
      alternative when used in the capacity to relieve caval obstruction. A case is
      reported in which a young woman with Klippel-Trenaunay syndrome has exercise
      intolerance and associated hypotensive cardiovascular collapse caused by inferior
      vena caval thrombosis. Recanalization of her inferior vena cava was successfully
      achieved and subsequently maintained through the placement of two Wallstents
      across the lesion. Although most venous stenting procedures have thus far been
      used in the treatment of venous obstruction caused by malignancy, inferior vena
      cava stenting in this patient with inferior vena caval thrombosis and Klippel
      Trenaunay syndrome suggests that venous stenting might offer an alternative
      therapeutic modality in treating a broader spectrum of occlusive venous disease.

PMID- 9240338
TI  - Revascularization of cerebral ischemia after previous bilateral extracranial
      intracranial bypass procedures.
AB  - Extracranial-intracranial (EC-IC) bypass grafting procedures were specially
      designed for treatment of bilateral internal carotid artery occlusion. When
      performed in an expeditious manner, EC-IC bypass procedures have produced
      effective and durable results, despite the recent disfavor given to this
      procedure. This communication reports a 68-year-old white man who developed
      generalized cerebral ischemia manifested as confusion, incoherence,
      disorientation, ataxia, and numerous episodes of syncope daily. A cerebral
      angiogram revealed bilateral external carotid arteries and left solitary
      vertebral artery critical stenosis. Transcranial Doppler study demonstrated
      reduction of cerebral and vertebral-basilar perfusion. However, the patient's EC
      IC bypass graft had remained patent since 1985. The patient's recurrent symptoms
      of global ischemia and syncope resolved after carotid endarterectomy, vein patch
      external carotid artery, and vertebral-to-common carotid artery transposition.
      This report reiterates the value of the EC-IC bypass procedure and presents the
      surgical management of symptomatic external carotid and vertebral artery stenosis
      in patients after EC-IC bypass procedures.

PMID- 9240339
TI  - Anomalous branch of the internal carotid artery maintains patency distal to a
      complete occlusion diagnosed by duplex scan.
AB  - A 67-year-old man had symptoms of peripheral vascular disease and was noted to
      have a carotid bruit. Duplex ultrasound examination of the neck demonstrated a
      short segmental occlusion of the proximal internal carotid artery (ICA) with
      antegrade flow distal to the occlusion maintained by an anomalous branch of the
      ICA. Angiography confirmed the findings and suggested that the branch was from
      the distribution of the occipital artery. The ICA findings were surgically
      proved, and endarterectomy was successfully performed without complication. This
      case reinforces the usefulness of duplex ultrasonography of the carotid arteries
      and is a rare situation in which a completely occluded ICA can be repaired with a
      good clinical outcome.

PMID- 9240340
TI  - A lateral approach to the below-knee popliteal artery without resection of the
      fibula.

PMID- 9240341
TI  - Regarding "Hemodynamic and clinical improvement after superficial vein ablation
      in primary combined venous insufficiency with ulceration".

PMID- 9240342
TI  - Branham's sign is an exaggerated Bezold-Jarisch reflex of arteriovenous fistula.

PMID- 9240343
TI  - Discovery of potent nonpeptide vitronectin receptor (alpha v beta 3) antagonists.

PMID- 9240344
TI  - Synthesis and nicotinic acetylcholine receptor binding properties of exo-2-(2'
      fluoro-5'-pyridinyl)-7-azabicyclo-[2.2.1]heptane: a new positron emission
      tomography ligand for nicotinic receptors.

PMID- 9240346
TI  - Designing combinatorial library mixtures using a genetic algorithm.
AB  - The design of combinatorial mixture libraries should take account of a number of
      factors. This paper describes the application of a genetic algorithm to
      optimizing the diversity of libraries while minimizing the effort that will be
      needed to deconvolute the biological hits by mass-spectroscopic techniques. It
      differs from previous applications of genetic algorithms to combinatorial library
      design in that each chromosome encodes an entire library with the result that
      properties of the library are optimized. Our method is such that it is easily
      extensible to optimizing the distributions of any number of physical or other
      properties of the library. The method allows for the combinatorial constraint
      inherent in mixtures that every substituent at each diversity site must occur in
      combination with every substituent at every other site. We present results
      showing that the genetic algorithm can produce good library designs in timely
      manner.

PMID- 9240345
TI  - Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine
      tyrosine kinase inhibitors.
AB  - Screening of a compound library for inhibitors of the fibroblast growth factor
      (FGFr) and platelet-derived growth factor (PDGFr) receptor tyrosine kinases led
      to the development of a novel series of ATP competitive pyrido[2,3-d]pyrimidine
      tyrosine kinase inhibitors. The initial lead, 1-[2-amino-6-(2,6
      dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3- tert-butylurea (4b, PD-089828),
      was found to be a broadly active tyrosine kinase inhibitor. Compound 4b inhibited
      the PDGFr, FGFr, EGFr, and c-src tyrosine kinases with IC50 values of 1.11, 0.13,
      0.45, and 0.22 microM, respectively. Subsequent SAR studies led to the synthesis
      of new analogs with improved potency, solubility, and bioavailability relative to
      the initial lead. For example, the introduction of a [4-(diethylamino)butyl]amino
      side chain into the 2-position of 4b afforded compound 6c with enhanced potency
      and bioavailability. Compound 6c inhibited PDGF-stimulated vascular smooth muscle
      cell proliferation with an IC50 of 0.3 microM. Furthermore, replacement of the 6
      (2,6-dichlorophenyl) moiety of 4b with a 6-(3',5'-dimethoxyphenyl) functionality
      produced a highly selective FGFr tyrosine kinase inhibitor 4e. Compound 4e
      inhibited the FGFr tyrosine kinase with an IC50 of 0.060 microM, whereas IC50s
      for the inhibition of the PDGFr, FGFr, EGFr, c-src, and InsR tyrosine kinases for
      this compound (4e) were all greater than 50 microM.

PMID- 9240347
TI  - Design, synthesis, and biological evaluation of new growth inhibitors of
      Trypanosoma cruzi (epimastigotes).
AB  - As a continuation of our project aimed at the search for new chemotherapeutic
      agents against Chagas' disease, several drugs structurally related to the insect
      growth regulator Fenoxycarb and the naturally occurring juvenile hormone of
      insects were designed, synthesized, and evaluated as antiproliferative agents
      against the parasite responsible of this disease. Isoprenoid derivatives
      (compounds 33, 34, 36, and 37) were potent growth inhibitors of Trypanosoma cruzi
      epimastigotes. In addition, taking into account the high activity observed for
      compound 30 and the inhibitory action of related compounds, the allyl ether
      moiety bonded at the polar extreme of these inhibitors proved to be a promising
      group for the design of new drugs.

PMID- 9240348
TI  - Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on
      tubulin polymerization and cancer cell growth.
AB  - A new series of estradiol analogs was synthesized in an attempt to improve on the
      anticancer activity of 2-methoxyestradiol, a naturally occurring mammalian
      tubulin polymerization inhibitor. The compounds were evaluated as inhibitors of
      tubulin polymerization and the binding of [3H]colchicine to tubulin, as well as
      for in vitro cytotoxicity in human cancer cell cultures. Overall, the most potent
      of the new compounds were 2-(2',2',2'-trifluoroethoxy)-6-oximinoestradiol, 2
      ethoxy-6-oximinoestradiol, and 2-ethoxy-6-methoximinoestradiol. These agents
      lacked significant affinity for the estrogen receptor. The cytotoxicities of the
      compounds correlated in general with their abilities to inhibit tubulin
      polymerization, thus supporting inhibition of tubulin polymerization as the
      primary mechanism causing inhibition of cell growth.

PMID- 9240349
TI  - 2-Cyclopropylindoloquinones and their analogues as bioreductively activated
      antitumor agents: structure-activity in vitro and efficacy in vivo.
AB  - A series of 2-cycloalkyl- and 2-alkyl-3-(hydroxymethyl)-1-methylindoloquinones
      and corresponding carbamates have been synthesized and substituted in the 5
      position with a variety of substituted and unsubstituted aziridines. Cytotoxicity
      against hypoxic cells in vitro was dependent upon the presence of a 5-aziridinyl
      or a substituted aziridinyl substituent for 3-hydroxymethyl analogues. The
      activity of 5-methoxy derivatives was dependent upon the presence of a 3
      (carbamoyloxy)methyl substituent. Increasing the steric bulk at the 2-position
      reduced the compounds' effectiveness against hypoxic cells. A 2-cyclopropyl
      substituent was up to 2 orders of magnitude more effective than a 2-isopropyl
      substituent, suggesting possible radical ring-opening reactions contributing to
      toxicity. Nonfused 2-cyclopropylmitosenes were more effective than related fused
      cyclopropamitosenes reported previously. The reduction potentials of the
      quinone/semiquinone one-electron couples were in the range -286 to -380 mV. The
      semiquinone radicals reacted with oxygen with rate constants 2-8 x 10(8) dm3 mol
      1 s-1. The involvement of the two-electron reduced hydroquinone in the mediation
      of cytotoxicity is implicated. The most effective compounds in vitro were the 2
      cyclopropyl and 5-(2-methylaziridinyl) derivatives, and of these, 5-(aziridin-1
      yl)-2-cyclopropyl-3-(hydroxymethyl)-1-methylindole-4 ,7-dione (21) and 3
      (hydroxymethyl)-5-(2-methylaziridin-1-yl)-1,2-dimethylindole+ ++-4,7-dione (54)
      were evaluated in vivo. Both compounds showed antitumor activity both as single
      agents and in combination with radiation, with some substantial improvements over
      EO9 (3) at maximum tolerated doses and as single agents against the RIF-1 tumor
      model and comparable efficacy in the KHT tumor model.

PMID- 9240350
TI  - A novel series of 2,5-substituted tryptamine derivatives as vascular 5HT1B/1D
      receptor antagonists.
AB  - The design, synthesis, and activity of a novel series of 2,5-substituted
      tryptamine derivatives at vascular 5HT1B-like receptors is described. Several
      important auxiliary binding sites of the 5HT1B-like receptor have been proposed
      following various modifications to the 2-substituent and especially to the
      methylene- or ethylene-linked 5-side chain. Careful design of new molecules based
      on a proposed pharmacophoric model of the 5HT1B-like receptor has resulted in the
      discovery of ethyl 3-[2-(dimethylamino)ethyl]-5-[2-(2, 5-dioxo-1
      imidazolidinyl)ethyl]-1H-indole-2-carboxylate (40), a highly potent, silent,
      competitive, and selective antagonist which shows affinity at the vascular 5HT1B
      like receptors only. Changes to the size of the 2-ester substituent have a
      significant effect on affinity at the 5HT1B-like receptor and other receptors.
      Prudent placement of the carbonyl substituent in the heterocycle of the 5-side
      chain is crucial for good affinity and selectivity over the 5HT2A and other
      receptors. Several key structural and electronic features were identified which
      are crucial for producing antagonism within a tryptamine-based series. An
      electron deficient indole ring system appears essential in order to achieve
      antagonism, and this is achieved by the inclusion of electron-withdrawing groups
      at the 2-position of the indole ring. The molecule displacement within the
      receptor resulting from the inclusion of the bulky 2-substituents also enhances
      antagonism as this results in the removal of the pi electron density of the
      indole ring from the region of the receptor normally occupied by the indole ring
      of 5HT. There also appears to be a structural requirement on the side chain
      incorporating the protonatable nitrogen, and this is achieved by the inclusion of
      the bulky 2-ester group which neighbors the 3-ethylamine side chain.

PMID- 9240351
TI  - Synthesis and anti-HIV-1 activity of a series of 1-alkoxy-5-alkyl-6
      (arylthio)uracils.
AB  - A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for
      their ability to inhibit HIV-1 replication. Treatment of 2-alkyl-3,3
      bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by
      reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N
      alkoxy-N'-((2-alkyl-3,3-bis(methylthio)acryloyl)ureas (10a-z) in good to
      excellent yields. Cyclization of 10a-z in AcOH containing a catalytic amount of p
      TsOH produced 1-alkoxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z
      with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5
      alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6
      (methylsulfinyl)thymine (12y), which were subsequently reacted with an
      appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6
      (arylthio)uracils (14-49). Substitution at the 3- and 5-positions of the C-6
      (phenylthio) ring by two methyl groups significantly increased its original anti
      HIV-1 activity (EC50: 6-((3,5-dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil
      (18), 0.064 microM; 6-((3,5-dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5
      isopropyluracil++ + (23), 0.19 microM). Among the various alkoxy substituents at
      the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1
      activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of
      HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23.
      Introduction of an isopropyl group at C-5 of the uracil base also remarkably
      enhanced the activity. When compound 18 was incubated with a rat liver homogenate
      preparation, no metabolite was observed, thus confirming the metabolic stability
      of the N-O bond in these 1-alkoxyuracils.

PMID- 9240352
TI  - 4-Heterocyclylpiperidines as selective high-affinity ligands at the human
      dopamine D4 receptor.
AB  - 5-(4-Chlorophenyl)-3-(1-(4-chlorobenzyl)piperidin-4-yl)pyrazole (3) was
      identified from screening of the Merck sample collection as a human dopamine D4
      (hD4) receptor ligand with moderate affinity (61 nM) and 4-fold selectivity over
      human D2 (hD2) receptors. Four separate parts of the molecule have been examined
      systematically to explore structure-activity relationships with respect to hD4
      affinity and selectivity over other dopamine receptors. It was found that the 4
      chlorophenyl group attached to the pyrazole is optimal, as is the 4-substituted
      piperidine. The lipophilic group on the basic nitrogen is more amenable to
      change, with the optimal group found to be a phenethyl. The aromatic heterocyle
      can be altered to a number of different groups, with isoxazoles and pyrimidines
      showing improved affinities. This heterocycle can also be advantageously
      alkylated, improving the selectivity of the compounds over D2 receptors. It is
      hypothesized that the conformation around the bond joining the aromatic
      heterocycle to the piperidine is important for D4 affinity, based on crystal
      structures of isoxazoles (29 and 30) and on a conformationally constrained
      compound (28). Putting all the favorable changes together led to the discovery
      that 5-(4-chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)iso xazole
      (36) is a nanomolar antagonist at human dopamine D4 receptors with > 500-fold
      selectivity over hD2 and > 200-fold selectivity over hD3. Compound 36 is an
      antagonist of hD4 receptors with good oral bioavailability of 38%, a half life of
      2 h, and brain levels 10-fold higher than plasma levels.

PMID- 9240353
TI  - Stabilized analogs of thymopentin. 1. 4,5-Ketomethylene pseudopeptides.
AB  - The pentapeptide, thymopentin (Arg1-Lys2-Asp3-Val4-Tyr5) is known for its
      activity as an immunomodulating drug, but with limited half-life in plasma. In
      this first paper of a series of three studies, the synthesis of analogs
      stabilized at the peptide bond between the C-terminal amino acids via insertion
      of a ketomethylene moiety is described. N-Blocked pseudopeptides containing
      Val(k)Phe, Ala(k)Phe, and Val(k)Val units were prepared and attached to
      chloromethyl Merrifield resin via the carboxy terminal. Removal of the N-BOC
      group by trifluoroacetic acid was followed by sequential coupling with N-BOC
      dipeptides of aspartic acid to yield resin-bound N-BOC pseudotetrapeptides.
      Removal of N-BOC and coupling with N-BOC-r-N-tosylarginine followed by total
      cleavage of blocking groups and resin by HF afforded the target
      pseudopentapeptides. The analogs were found to compete favorably with thymopentin
      for binding to CEM cells, but binding was reduced by about 20-30% on average. All
      analogs showed significant enhancement of half-life versus thymopentin in mouse
      serum, but most showed only modest improvement in human serum. Insertion of
      proline or norleucine at position 2 in the chain caused a substantial increase in
      half-life (3-4-fold), while N-methylnorleucine conferred complete stability in
      the analogs.

PMID- 9240354
TI  - Stabilized analogs of thymopentin. 2. 1,2- and 3,4-ketomethylene pseudopeptides.
AB  - In this second paper in a series of three studies of stable analogs of
      thymopentin (Arg1-Lys2-Asp3-Val4-Tyr5), the synthesis of analogs stabilized at
      peptide bonds 1,2 and 3,4 via insertion of ketomethylene units is described. A
      tris(carbobenzyloxy)arginyl(k)norleucine pseudopeptide was synthesized and
      coupled to Asp-Val-Phe-resin units followed by HF cleavage to prepare Arg(k)Nle
      Asp-Val-Phe analogs. Preparation of N-BOC Asp(k)Val and N-BOC Asp(k)Ala units
      followed by coupling to Phe- or Tyr-resin units provided resin-bound
      pseudotripeptide substrates for attachment of various arginyl dipeptides.
      Cleavage from the resin afforded 3,4-ketomethylene-stabilized pseudopeptide
      analogs of thymopentin. The Arg-Lys-Asp(k)Val-Phe and Arg-Lys-Asp(k)Val-Tyr
      analogs were more strongly bound to CEM cells than thymopentin itself. There was
      significant enhancement of stability in serum for the analogs, especially those
      containing Arg(k)Nle or Arg-NMeLys moieties at the 1,2-peptide bond.

PMID- 9240355
TI  - Stabilized analogs of thymopentin. 3. Evaluation of ketomethylene pseudopeptides
      for antiarthritic properties.
AB  - This study analyzed the role of ketomethylene pseudopeptides of thymopentin as
      potential agents for the treatment of arthritis. The analogs were tested in vivo
      using assessment of inflammation and antibody production in the mouse type II
      collagen arthritis model and the rat adjuvant arthritis model. The compounds were
      also tested for immune-potentiating activity in vitro using induction of the
      lymphocyte marker, Thy-1.2, in mouse spleen cells and stimulation of T-cell
      proliferation. The results show that certain of the compounds exhibit disease
      remitting properties for arthritis as evidenced by reduction of paw swelling in
      the mouse and rat models and decreased incidence of disease in the mouse model.
      The active compounds were dose specific and represented a range in efficacy. In
      spite of effects on arthritis, type II collagen antibody levels were not altered
      in the mouse model. Selected compounds also exhibited immune potentiating
      properties as evidenced by induction of Thy-1.2 expression and stimulation of T
      cell proliferation. The absence of effect of the compounds on type II collagen
      antibody production suggests that the antiarthritic activity of the effective
      compounds results from alteration of cell-mediated immunity.

PMID- 9240356
TI  - A virtual screening approach applied to the search for trypanothione reductase
      inhibitors.
AB  - A prediction algorithm of the binding affinity of ligands to trypanothione
      reductase (TR), the enzyme replacing glutathione reductase in the metabolism of
      trypanosomatidae, has been used for the "virtual screening" of a data base of
      2500 molecular sketches and has detected several structures of putative TR
      ligands. Most of these compounds turned out to be micromolar inhibitors of TR, as
      predicted by the algorithm. While their inhibitory potencies are lower than those
      of previously reported compounds, one of the molecules reported here could
      represent the lead toward a structurally different class of TR inhibitors. The
      fully automated prediction algorithm converts the 2D molecular sketches into 3D
      ligand structures, explores the conformational space of the latter, and performs
      a grid-based, rigid-body docking of the resulting family of ligand conformations
      into the TR site, calculating enthalpic and entropic binding indexes and
      predicting the binding affinity. The docking model has also been used to obtain
      hints about the binding modes of TR ligands.

PMID- 9240357
TI  - Synthesis of racemic 6,7,8,9-tetrahydro-3-hydroxy-1H-1-benzazepine-2,5-diones as
      antagonists of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) receptors.
AB  - The synthesis and pharmacological properties of several racemic 6,7,8,9
      tetrahydro-3-hydroxy-1H-1-benzazepine-2,5-diones (THHBADs) are described.
      Synthesis was accomplished via a Schmidt reaction with 5,6,7,8-tetrahydro-2
      methoxynaphthalene-1,4-diones (THMNDs) followed by demethylation. THMNDs were
      prepared via a Diels-Alder reaction with 2-methoxybenzoquinone (5) or 2-bromo-5
      methoxybenzoquinone (14) and substituted 1,3-butadienes. The pharmacology of
      THHBADs was characterized by electrical recordings in Xenopus oocytes expressing
      rat brain NMDA and AMPA receptors. THHBADs are antagonists of NMDA and AMPA
      receptors with functional potency being dependent upon the substitution pattern
      on the tetrahydrobenzene moiety. The 7,8-dichloro-6-methyl (18a) and 7,8-dichloro
      6-ethyl (18b) analogs are the most potent THHBADs prepared and have apparent
      antagonist dissociation constants (Kb values) of 0.0041 and 0.0028 microM,
      respectively, for NMDA receptors and 0.51 and 0.72 microM, respectively, for AMPA
      receptors.

PMID- 9240358
TI  - Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse
      transcriptase. 6. 2-Indol-3-yl- and 2-azaindol-3-yl-dipyridodiazepinones.
AB  - Modification of the non-nucleoside inhibitor of HIV-1 reverse transcriptase
      nevirapine (Viramune) by incorporation of a 2-indolyl substituent confers
      activity against several mutant forms of the enzyme.

PMID- 9240359
TI  - Work and nonvocational domains of functioning in persons with severe mental
      illness: a longitudinal analysis.
AB  - In this study we sought to understand the relationship between obtaining
      competitive employment and changes in nonvocational domains of functioning
      (symptoms, substance abuse, hospitalizations, self-esteem, quality of life) in
      persons with severe mental illness. A group of 143 unemployed patients
      participating in a study of vocational rehabilitation programs were assessed in
      nonvocational areas of functioning at baseline and 6, 12, and 18 months later.
      Statistical analyses examined the relationship between work status at the follow
      up assessments and nonvocational functioning, controlling for baseline levels of
      nonvocational variables. Patients who were working at follow-up tended to have
      lower symptoms (particularly thought disorder and affect on the Brief Psychiatric
      Rating Scale), higher Global Assessment Scores, better self-esteem, and more
      satisfaction with their finances and vocational services than unemployed
      patients. Employment is associated with better functioning in a range of
      different nonvocational domains, even after controlling for baseline levels of
      functioning.

PMID- 9240360
TI  - Performance characteristics of chronic schizophrenia on attention tests sensitive
      to unilateral brain damage.
AB  - The aims of this study were to investigate the lateralization hypothesis of
      schizophrenia, comparing chronic schizophrenics with unilateral brain-damaged
      subjects and normal controls, using attentional tests sensitive to the unilateral
      brain damage. Three attentional tests with different modes of stimuli, two
      vigilance tasks that require the self-paced or nonself-paced responses of
      subjects and one divided attention task, were administered to 28 chronic
      schizophrenics, 26 right and 24 left unilateral brain-damaged subjects, and 20
      normal controls. The results indicated that schizophrenics performed a possible
      right-hemisphere damages pattern and also a left pattern in part, with failure of
      all tasks to show either pattern related to a number of differences between the
      three tasks. Furthermore, the attention deficits of schizophrenics are less than
      those of brain-damaged subjects but are clearly abnormal compared with the normal
      controls.

PMID- 9240361
TI  - The phenomenology of traumatic reactions to psychotic illness.
AB  - This study investigated whether a psychotic illness was associated with
      posttraumatic stress disorder (PTSD) symptomatology in 45 subjects recovering
      from hospitalization for a psychotic episode. Previous studies have suggested
      that the experience of psychosis and hospitalization is distressing and that PTSD
      may be a useful paradigm for the psychological response. Subjects were given
      questionnaires to evaluate PTSD symptoms, anxiety symptoms, and distress and
      intrusive memories associated with aspects of treatment and psychosis. Treatment,
      especially experiences involving a loss of control such as detention, and
      psychotic symptoms, particularly persecutory delusions, passivity phenomena, and
      visual hallucinations, were perceived as highly distressing. Twenty-two subjects
      (52%) met the criteria for a postpsychotic PTSD, with implications for
      recognition and management of secondary morbidity related to psychosis.

PMID- 9240362
TI  - Discriminating borderline from antisocial personality disorder in male patients
      based on psychopathology patterns and type of hostility.
AB  - Dimensions of psychopathology and patterns of hostility, as well as the
      relationship of hostility to psychopathology, were studied in 85 male young
      adults: 41 with borderline personality disorder (BPD) and 44 with antisocial
      personality disorder (APD). Diagnoses were based on DSM-III. The following
      instruments were also used: Brief Psychiatric Rating Scale, Hamilton Depression
      Rating scale, State-Trait Anxiety Inventory, and Hostility and Direction of
      Hostility Questionnaire. BPD patients compared with APD patients showed higher
      levels of overall psychopathology and depression, whereas both groups had equally
      high anxiety. Total hostility was quite high in both groups. However, BPD
      patients had more introverted hostility and APD patients had more extroverted
      hostility. In BPD patients, introverted hostility was related to overall
      psychopathology, depression, and trait anxiety, whereas in APD patients, no
      significant relationship of any type of hostility to various dimensions of
      psychopathology was observed. In conclusion, when comprehensively assessed, BPD
      patients can be discriminated from APD patients based on certain dimensions of
      psychopathology and differences in the direction of their hostility. Moreover,
      the relationship between psychopathology and hostility patterns suggests that the
      direction of patients' hostility plays an important role in the development of
      disorder-specific symptomatology.

PMID- 9240363
TI  - Psychological distress and bereavement.
AB  - Some 115 bereaved subjects (43 spouses, 39 adult children, and 33 parents) were
      followed-up prospectively over 12 months following the acute bereavement period.
      They completed the Zung Depression Scale, Spielberger's State and Trait Anxiety
      Measure, the GHQ-28, and Eysenck's Personality Inventory at four time points.
      With the exception of EPI-Extroversion, there was a significant decrease in all
      scores over the period encompassing the study. There were no differences between
      the three groups on any of the psychological variables measured. Scores on the
      Zung Depression Scale, state and trait anxiety, and neuroticism correlated
      significantly with a measure of core bereavement phenomenology, the Core
      Bereavement Items, at each time point for each group.

PMID- 9240364
TI  - Absorption, social desirability, and symptoms in a behavioral medicine
      population.
AB  - The relationships among absorption, social desirability, and psychological and
      somatic symptoms were examined in a clinical population of patients at a
      behavioral medicine clinic. Absorption, as measured by the Tellegen Absorption
      Scale, was significantly and positively related to the somatization and global
      distress indices of the Brief Symptom Inventory. However, absorption was
      negatively related to social desirability, as measured by the Marlowe-Crowne
      Scale. Global distress, but not somatization, also was negatively related to
      social desirability. After controlling for social desirability, global distress
      was marginally related to absorption. In addition, absorption interacted with a
      measure of how much patients were bothered by their primary symptom. Patients who
      had high absorption reported more somatic and global distress if they also
      reported being very bothered by their primary symptom than if they were less
      bothered by it. The results are discussed with respect to related research on
      absorption, social desirability, and symptoms.

PMID- 9240365
TI  - Underreporting of cocaine use at posttreatment follow-up and the measurement of
      treatment effectiveness.
AB  - Substance abusers, especially cocaine abusers, may underreport their substance
      use in outcome interviews. Follow-up interviews were conducted and urine
      specimens were obtained on 633 persons 9 months after admission to a 3-month
      cocaine treatment program. Although 422 (67%) reported no use of cocaine in the
      past 30 days, 134 of these (32%) had cocaine-positive urines. This group did not
      differ on most characteristics at intake or follow-up from the 288 with cocaine
      negative urines. The amount of treatment received did affect willingness to admit
      drug use. Of 132 treatment completers who reported no cocaine use at follow-up,
      21 (16%) had positive urines. Of 91 early dropouts who also reported no cocaine
      use, 36 (40%) had positive urines. This differential rate of underreporting had
      the effect of seriously underrepresenting the effectiveness of treatment
      completion as compared with little or no treatment.

PMID- 9240366
TI  - Neuroleptic dysphoria may be the missing link between schizophrenia and substance
      abuse.

PMID- 9240367
TI  - Paroxetine for secondary stuttering: further interaction of serotonin and
      dopamine.

PMID- 9240368
TI  - Neuronal responses to turtle head rotation in vitro.
AB  - Extracellular recordings were made during vestibular stimulation from an in vitro
      turtle brain stem in which the temporal bones remained attached. Under visual
      control, microelectrodes were slowly advanced into the vestibular nucleus (VN)
      while we rotated the brain and searched for a single isolated unit whose spike
      activity was modulated by the lateral semicircular canals. In some experiments,
      responses were shown to be due to stimulation of the lateral canals, either by
      positioning the brains in forward or backward pitch during horizontal rotation or
      by plugging the vertical canals with wax. VN neurons usually had low spontaneous
      activity and rectified sinusoidal responses to sinusoidal stimulation. Spike
      response histograms were averaged from many stimulus cycles and were then fit to
      a sine function. The fitted phase and amplitude parameters were plotted relative
      to stimulus frequency and amplitude. The sample of VN cells were quite
      heterogeneous. Using stimuli at 1 Hz, however, each cell's response phase was
      weakly correlated with the slope of the plots of response amplitude versus
      frequency so that a cell could be categorized as sensitive to velocity or
      acceleration and as sensitive to ipsiversive or contraversive rotation, depending
      on whether its phase was near -180 degrees, -90 degrees, 0 degrees, or 90
      degrees, and whether the gain exceeded 0.4 spikes/s per degrees/s. The properties
      of these VN cells suggest that there is substantial complexity in the vestibular
      responses at this first site of central vestibular processing. These data are
      compared to that of other species where such vestibular signals play an important
      role in oculomotor and spinal reflexes.

PMID- 9240369
TI  - The alpha1 subunit of laminin-1 promotes the development of neurons by
      interacting with LBP110 expressed by neural crest-derived cells immunoselected
      from the fetal mouse gut.
AB  - A plasmalemmal protein, LBP110, which binds to the alpha1 chain of laminin-1, is
      acquired by the neural crest-derived precursors of enteric neurons after they
      colonize the gut. We tested the hypothesis that laminin-1 interacts with LBP110
      to promote enteric neuronal development. The effects of laminin-1 on neuronal
      development were studied in cultures of cells immunoselected from fetal mouse gut
      (E14-15) with antibodies to LBP110 or p75NTR, a marker for enteric crest-derived
      cells. No matter which antibody was used, the development of cells expressing
      neuronal markers was increased three- to fourfold by culturing the cells on a
      laminin-1-containing substrate. To determine whether this effect of laminin-1 is
      due to the selective adherence of a neurocompetent subset of precursors,
      immunoselected cells were permitted to preadhere to poly-D-lysine. Addition of
      soluble laminin-1 24 h later promoted neuronal but not glial development. The
      laminin-1-induced increment in neuronal development was abolished both by a
      peptide containing the sequence of the LBP110-binding domain, IKVAV, and by
      antibodies to laminin alpha1 that recognize the IKVAV domain. Neither reagent
      affected the total number of cells. In contrast, the response to laminin-1 was
      not affected by control peptides, preimmune sera, or antibodies to laminin beta1.
      Laminin-1 transiently induced the expression of nuclear Fos immunoreactivity;
      this action was blocked specifically by the IKVAV peptide. These data are
      consistent with the hypothesis that LBP110 interacts with the IKVAV domain of
      laminin alpha1 to promote the differentiation of neurons from enteric crest
      derived precursors.

PMID- 9240370
TI  - Proctolin's role in neurally evoked contractions of the locust oviducts.
AB  - The effects of proctolin (RYLPT) on neurally evoked contractions of locust
      oviduct muscle were studied to examine the role of proctolin as a cotransmitter.
      Increasing the number of stimuli in a burst (from one to 30 stimuli) resulted in
      an increase in amplitude of contraction of locust oviduct muscle. Proctolin was
      capable of increasing the amplitude of neurally evoked contractions at lower
      stimulus regimes (one- and two-stimulus bursts) but did not do so at higher
      stimulus regimes (five- and 10-stimulus bursts). The effects of proctolin were
      dose dependent within the one- and two-stimulus regimes, with thresholds at 10(
      9) M and maxima at 2.5 x 10(-8) M. Addition of proctolin increased the basal
      tonus and size of a postcontraction relaxation of the oviduct muscle in a dose
      dependent manner during all stimulus regimes. However, the effect of proctolin on
      basal tonus and the postcontraction relaxation was much less at the higher
      stimulus regimes. Previously, several proctolin analogues have been tested for
      their ability to antagonize proctolin-induced contractions of the oviduct muscle.
      Since proctolin is proposed to be a cotransmitter at this neuromuscular junction,
      one of these analogues, cycloproctolin, was used to antagonize proctolin's
      effects on neurally evoked contractions. In the presence of the antagonist, the
      maximum amplitude induced by application of proctolin was decreased by 22.7%,
      while the proctolin-induced increase in basal tonus was decreased by 45.8%.
      Finally, the maximum increase in the size of the postcontraction relaxation
      caused by proctolin was lowered by 32.0%. The results of the present study show
      that exogenously applied proctolin is an excitant of the oviduct muscle at lower,
      rather than higher, stimulus regimes, and this latter inaction may be due to the
      corelease of endogenous proctolin during increased neural stimulation.

PMID- 9240371
TI  - A nuclear localization signal targets proteins to the retrograde transport
      system, thereby evading uptake into organelles in aplysia axons.
AB  - The turnover of soluble proteins in axons and terminals is effected by replacing
      used proteins with newly synthesized constituents from the cell body. To
      investigate this complex process, which is especially important during nerve
      regeneration, we microinjected proteins into varicosities on axons of Aplysia
      neurons in vitro. When human serum albumin (HSA) coupled to rhodamine (r) was
      injected, it initially filled the varicosity; within seconds, however, it began
      to accumulate in packets and by 15 min was punctate. A similar pattern was
      observed after injecting soluble proteins from extruded axoplasm. In contrast,
      when we injected rHSA covalently attached to the SV-40 nuclear localization
      sequence (sp), the distribution was never punctate and the rHSA-sp was
      retrogradely transported from the varicosity to the cell body and into the
      nucleus. Electron microscopy of varicosities injected with HSA-gold showed that
      >90% of the particles were inside vacuoles and multivesicular bodies. These
      organelles probably function as storage rather than degradatory sites since they
      did not contain acid phosphatase. In contrast, when HSAsp-colloidal gold was
      injected, only 25% of the particles were in organelles. Thus, HSA and resident
      axonal proteins can be removed from axoplasm by uptake into organelles. The
      presence of a nuclear localization sequence (the sp) may avoid uptake by
      providing access to the retrograde transport/nuclear import pathway.

PMID- 9240373
TI  - Adenoviral vector-directed expression of neurotrophin-3 in rat dorsal root
      ganglion explants results in a robust neurite outgrowth response.
AB  - The neurotrophins are a family of proteins that promote neuronal survival and
      neurite outgrowth during development and can also enhance the regeneration of
      injured adult neurons. The local and continuous delivery of these proteins at the
      site of injury is problematic, since this requires repeated intraparenchymal
      injections or the use of invasive canula-micropump devices. In the present study
      we report the generation and characterization of an adenoviral vector for a
      member of the neurotrophins, neurotrophin-3 (Ad-NT-3). Using Ad-NT-3, we examined
      the expression and biological activity of NT-3 in dorsal root ganglia (DRG)
      explant cultures. Gene transfer with Ad-NT-3 results in the synthesis of genuine
      NT-3 and in a dosage-dependent neurite outgrowth response in DRG explants.
      Transduction of DRG explants with a viral vector dosage of 5 x 10(5) to 5 x 10(6)
      plaque-forming units induced the formation of a dense halo of neurites comparable
      to outgrowth observed following the addition of 100 ng/mL exogenous NT-3. In
      addition, a single infection with Ad-NT-3 produced biologically active NT-3 for
      at least 20 days in culture, as evidenced by continued neurite extension. This
      indicates that adenoviral vector-mediated expression of NT-3 results in high
      level production of biologically active NT-3 and could therefore be used as a
      strategy to promote the regeneration of injured peripheral and central nerve
      projections.

PMID- 9240372
TI  - Concentration-dependent stimulation and inhibition of growth cone behavior and
      neurite elongation by protein kinase inhibitors KT5926 and K-252a.
AB  - We examined the concentration- and time-dependent effects of two related protein
      kinase inhibitors, KT5926 and K-252a, on neurite formation and nerve growth cone
      migration of chick embryo sensory neurons. The effects of these drugs on neurite
      formation over an 18-h period were dissimilar. KT5926 stimulated neurite
      formation at concentrations between 100 and 500 nM and inhibited neurite
      formation at 5 microM. K-252a had no stimulatory effects on neurite formation,
      and it inhibited neurite formation at concentrations above 50 nM. This difference
      may occur because K-252a inhibits activation of the nerve growth factor receptor
      trk A, while KT5926 does not inhibit trk A. Both drugs, however, had similar
      immediate effects on growth cone migration. Growth cone migration and
      lamellipodial spreading were rapidly stimulated by 500 nM concentrations of
      KT5926 and K-252a. At 2 microM levels of either drug, growth cone spreading was
      still stimulated, but growth cone migration was inhibited by both drugs. These
      results show that changes in protein phosphorylation/dephosphorylation can
      rapidly regulate the cellular machinery that is responsible for driving growth
      cone migration and neurite elongation. The different effects of 2 microM
      concentrations of either KT5926 or K-252a on growth cone spreading versus
      migration suggests that the actin-dependent protrusive motility of the growth
      cone leading margin is regulated differently by changes in protein
      phosphorylation and dephosphorylation than the cytoskeletal mechanism that drives
      neurite elongation.

PMID- 9240374
TI  - Mass and functional capacity of regenerating muscle is enhanced by myoblast
      transfer.
AB  - Morphology and functional capacity of homotopically transplanted extensor
      digitorum longus muscles (EDL) of adult SCID mice that received 1 x 10(6)
      myoblasts [stably transfected to express nuclear localizing beta-galactosidase
      under the control of the myosin light-chain 3F promoter/enhancer] 2 days
      posttransplantation were evaluated 9 weeks after transplantation, to determine
      whether the injection of exogenous myoblasts had an effect on muscle
      regeneration. Regenerated muscles that received exogenous myoblasts were compared
      to similarly transplanted muscles that received (a) no further treatment, or (b)
      sham injection of the vehicle (without myoblasts) and to unoperated EDL. Nine
      weeks after myoblast transfer, myofibers containing donor-derived nuclei could be
      identified after staining with X-gal solution. Judging from its size and poor
      functional performance compared to muscles subjected to transplantation only,
      sham injection provided a secondary trauma to the regenerating muscle from which
      it failed to fully recover. In comparison to the sham-injected muscle, the
      myoblast-injected muscles weighed 61% more and had 50% more myofibers and 82%
      more cross-sectional area occupied by myofibers at the muscles' widest girths.
      Their absolute twitch and tetanic tensions were threefold and twofold greater,
      respectively, and their specific twitch and tetanic tensions were 71% and 50%
      greater, respectively, than those of sham-injected muscles. In many parameters,
      the regenerating muscle subjected to myoblast transfer equaled or exceeded those
      of muscles that were transplanted only (received only one trauma). Absolute
      twitch and tetanic tensions were 73% and 65% greater, respectively, and specific
      twitch tensions of the muscles receiving myoblasts were 50% greater than forces
      generated by muscles subjected to whole-muscle transplantation only.

PMID- 9240375
TI  - Mutation of the central nervous system neuroblast proliferation repressor ana
      leads to defects in larval olfactory behavior.
AB  - In the developing nervous system, interactions between glia and immature neurons
      or neuroblasts regulate axon pathfinding, migration, and cell division, and
      therefore affect structure and function. Glial control of neuroblast cell
      division has been documented by studies of the anachronism (ana) gene of
      Drosophila melanogaster. ana encodes a glycoprotein which, in the developing
      larval central nervous system, is secreted by glia that neighbor regulated
      neuroblasts. Mutations in ana lead to premature neuroblast proliferation in the
      larval brain. Examination of lacZ expression from an ana enhancer trap line as
      well as detection of the ana protein show that ana is also expressed in the
      larval antennal-maxillary complex (AMC) at all larval stages. As previously
      reported for the central nervous system, ana expression in the AMC appears to be
      confined to glial cells. Larval olfactory system function in ana mutants was
      assayed in a behavioral paradigm. When tested with the three different
      chemoattractants, third instar ana9 mutant larvae showed diminished olfactory
      response compared to controls. Examination of a second ana allele revealed
      aberrant olfactory response to ethyl acetate, demonstrating that more than one
      mutation in ana can give rise to abnormal larval olfactory behavior. Assays of
      early first instar ana9 mutant larvae revealed defective olfactory behavior,
      implying that the olfactory phenotype stems from early larval AMC and/or
      embryonic origins. This is consistent with proliferation analysis in the early
      larval AMC region which uncovered a significantly higher number of S-phase cells
      in ana9 mutants.

PMID- 9240376
TI  - The road less traveled -- the decline in numbers of clinical researchers.

PMID- 9240377
TI  - The concentration of calmodulin present in parotid cells.

PMID- 9240378
TI  - IADR in years to come.

PMID- 9240379
TI  - Amorphous calcium phosphate: the contention of bone.

PMID- 9240380
TI  - Craniofacial and TMJ effects after glutamate and TRH microsphere implantation in
      proximity to trigeminal motoneurons of growing rats.
AB  - The sequelae of sustained, in vivo delivery of two important neurotransmitter
      substances, glutamate and thyrotropin-releasing hormone (TRH), upon craniofacial
      growth and development have previously not been investigated. Our purpose was to
      document and compare the relative effects of glutamate and TRH microspheres
      stereotactically placed in proximity to trigeminal motoneurons within the
      trigeminal motor nucleus. The following null hypotheses were tested: (1) TRH
      microspheres in proximity to trigeminal motoneurons have no significant effect
      upon the craniofacial skeleton, and (2) there are no significant differences
      between the relative effects of chronic, long-term delivery of glutamate and TRH
      upon the neuromusculoskeletal system of growing rats. Forty male Sprague-Dawley
      rats were divided into 4 experimental groups (glutamate microspheres, TRH
      microspheres, blank microspheres, sham surgeries) and underwent stereotactic
      neurosurgery at 35 days; 5 rats of each group were killed at 14 and 21 days for
      data collection. Histology revealed that implants were clustered in the pontine
      reticular formation, close to the ventrolateral tegmental nucleus. Both glutamate
      and TRH rats had implant-side deviation of their facial skeleton and snout
      regions; 4 x 2 ANOVA and post hoc t-tests revealed significant (P < or = 0.05,
      0.01) differences between groups and sides for motoneuron count, muscle weight,
      and osteometric data. TRH rats also demonstrated larger implant-side TMJ discs
      and mandibular fossae in comparison with the other groups. The stated null
      hypotheses were therefore rejected.

PMID- 9240381
TI  - Sensitivity of periodontal pathogens to the bactericidal activity of synthetic
      protegrins, antibiotic peptides derived from porcine leukocytes.
AB  - Protegrins, small peptides (1900 to 2160 daltons) isolated from porcine
      leukocytes, are bactericidal against a broad range of medical pathogens in vitro
      under conditions which reflect the extracellular milieu. The purpose of this
      study was to determine whether Gram-negative, facultative periodontal pathogens
      were sensitive to the protegrins. Synthetic L- and D-enantiomers of protegrin 1
      (PG-1 and D-PG-1, respectively), and L-enantiomers of protegrins 2, 3, and 5 (PG
      2, PG-3, and PG-5) were tested against Actinobacillus actinomycetemcomitans
      (three strains) and Capnocytophaga spp. (three strains). Strains of both A.
      actinomycetemcomitans and Capnocytophaga spp. were sensitive to PG-1, and
      exhibited ED99 (dose at which 99% killing was observed after 1 hr at 37 degrees
      C) of 0.5 to 3 microg/mL and 4 to 19 microg/mL, respectively. The D-form and the
      L-form were equally effective. Serum (above 5% v/v) inhibited the bactericidal
      effects of 10 microg/mL PG-1, but the inhibitory effect was overcome by
      concentrations of PG-1 at 100 microg/mL. Different patterns of sensitivity were
      observed when the effects of PG-1, D-PG-1, PG-2, PG-3, and PG-5 were compared
      against A. actinomycetemcomitans and the Capnocytophaga. We conclude that
      protegrins may be useful antimicrobial agents in therapy against periodontal
      infections.

PMID- 9240382
TI  - Recombinant human bone morphogenetic protein-2 promotes wound healing in rat
      periodontal fenestration defects.
AB  - Although there is considerable interest in the use of bone morphogenetic protein
      (BMP) to promote periodontal regeneration, little is known of its effects on the
      early stages of wound healing. The aim of this study was to investigate the
      effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an early
      stage of post-operative wound healing and following complete healing (10 and 38
      days, respectively) in a rat model of periodontal regeneration. The buccal
      aspects of molar roots were carefully denuded of their periodontal ligament
      through a bony window created in the mandibles of Wistar rats under general
      anesthesia. After the root surfaces were acid-conditioned, a 10-microL quantity
      of 50 microg/mL rhBMP-2 in a collagen gel solution was placed into the surgically
      created defect in test animals; in controls, either a 10-microL quantity of only
      collagen gel was received, or the defect was untreated. Animals were killed 10
      days or 38 days after surgery and the tissues processed for histological
      examination. Transverse 5-microm sections were stained for the identification of
      new bone, cementum, and collagen fiber formation. In the 10-day study groups, new
      bone formation over the second molar and beyond the defect was significantly
      increased in the test group (p < 0.02), although there was no evidence of
      increased ankylosis. RhBMP-2 stimulated more than twice the area of cementum
      growth coronally compared with controls (712 +/- 286 microm2 and 258 +/- 57
      microm2, respectively). Connective tissue attachment, including the number and
      width of collagen bundles, was similar in both test and controls. Complete
      healing without any evidence of ankylosis had occurred in all animals 38 days
      post-operatively, and no significant differences were observed between test and
      control groups. In conclusion, a single dose of rhBMP-2 increased the rate of
      normal intramembranous bone formation and selectively enhanced cementum formation
      coronally during early wound healing. However, the finding that rhBMP-2 induced
      bone formation at some distance from the defect suggests the importance of
      developing a suitable delivery system to maintain the concentration of BMP-2 at
      the site of implantation for potential therapeutic use.

PMID- 9240383
TI  - Intermittent parathyroid hormone administration stimulates bone formation in the
      mandibles of aged ovariectomized rats.
AB  - Intermittent administration of parathyroid hormone (PTH) is known to stimulate
      bone formation in many skeletal sites and is being investigated as a possible
      therapeutic agent for the treatment of osteopenic conditions, including post
      menopausal osteoporosis. The purpose of this study was to determine the ability
      of PTH to stimulate bone formation in the mandibles of aged ovariectomized (Ovx)
      rats, and the results are compared with a site in the appendicular skeleton
      (humerus). The Ovx rat is a useful model of estrogen deficiency, replicating many
      aspects of post-menopausal osteoporosis. Female rats were ovariectomized or sham
      operated, and one year later a group of the ovariectomized rats was treated with
      the 1-34 fragment of human PTH daily, five days a week for 10 weeks. During the
      experiment, the animals were given fluorochrome bone markers for
      histomorphometry. More than one year after ovariectomy or sham surgery, there
      were few differences in the histomorphometric indices of bone formation in the
      humerus or mandible. PTH treatment had no effect on dentin formation, measured in
      the mandibular incisor; however, most indices of bone formation-including the
      double-labeled surface, mineralizing surface, mineral appositional rate, new bone
      area, and surface-referent bone formation rates-were substantially greater in the
      PTH-treated group compared with both the Ovx and the Sham controls measured at
      the periosteal and endocortical surfaces of the humerus and the periosteal and
      cancellous bone surfaces of the mandible. In addition, bone formation at the
      alveolar crest, particularly on the buccal side, was greater in the PTH-treated
      group. The results from this study demonstrate that systemic intermittent PTH
      treatment stimulates bone formation in the mandibles in aged, estrogen-deficient
      animals.

PMID- 9240384
TI  - Pathway for uptake and degradation of X-prolyl tripeptides in Streptococcus
      mutans VA-29R and Streptococcus sanguis ATCC 10556.
AB  - The growth of Streptococcus mutans and Streptococcus sanguis in the oral
      environment requires that these micro-organisms be able to degrade salivary
      proteins and to assimilate the resulting peptides as an amino nitrogen source.
      Our research is aimed at the definition of the proteolytic enzyme systems in
      these oral streptococci which allow them to utilize such substrates. In the
      present work, the nature of the hydrolytic activity expressed by S. mutans VA-29R
      and S. sanguis ATCC 10556 against X-Pro4-nitroanilide and X-Pro-Y tripeptide
      substrates was investigated. This activity was predominantly associated with a
      cytoplasmic dipeptidyl peptidase which preferentially catalyzes the release of an
      N-terminal dipeptide from substrates in which proline is the penultimate residue.
      These streptococci also possess a second cytoplasmic peptidase, pepD, which
      catalyzes the hydrolysis of X-Pro dipeptides. We found that Gly-Pro-Ala or Ala
      Pro-Gly were transported into the bacterial cells only when an energy source such
      as glucose was present. Peptide uptake was time-dependent, and selective exodus
      of peptide-derived amino acids from the bacterial cells occurred during peptide
      uptake. Results from these studies provide evidence that S. mutans VA-29R and S.
      sanguis ATCC 10556 possess a pathway for the complete degradation of X-Pro
      tripeptides. Transport of the peptides into cells prior to hydrolysis provides an
      efficient way by which all amino acids of a peptide may be obtained at an energy
      expense equivalent to that associated with the transport of just one amino acid.
      In light of the abundance of proline in salivary polypeptides, this degradative
      pathway could be an important component in the proteolytic pathway for salivary
      polypeptide utilization in these oral streptococci.

PMID- 9240385
TI  - Solubility control of thin calcium-phosphate coating with rapid heating.
AB  - The thin calcium-phosphate (Ca-P) coatings produced by the ion-beam-mixing method
      instead of the plasma-spraying method have been found to be amorphous, resulting
      in films that easily dissolved in simulated body fluid. These coatings
      crystalized with conventional heat treatment in an electric furnace but tended to
      crack easily. Therefore, the purpose of this study was to find a suitable heat
      treatment that controls the solubility of Ca-P coatings without weakening their
      adhesion to titanium (Ti) substrate. Thin coatings (approximately 1 microm) were
      coated onto Ti substrates, followed by heat treatment in a conventional furnace
      and rapid heating by infrared radiation and laser radiation. X-ray diffraction
      analysis revealed untreated films to be amorphous but to become crystalline after
      being heated in a furnace at 500 degrees C, heated rapidly with infrared
      radiation higher than 600 degrees C and with laser radiation at output power of
      10W. We evaluated solubility by estimating the film thickness after immersion in
      simulated body fluid for 5 weeks: Untreated films dissolved within 1 day.
      Coatings treated with infrared radiation at 600 degrees C dissolved minimally.
      Cracks were observed in coatings subjected to infrared radiation at 800 degrees C
      and furnace-heated at 500 degrees C. Coatings treated with laser radiation tended
      to dissolve easily, with non-uniform surface degradation. X-ray photoelectron
      spectroscopy analysis at the interface between the coating and the Ti substrate
      showed that cracks were the result of decreased Ca-implanted layers and too much
      growth of Ti-P compounds. No difference was recognized in the Ti-oxidation state
      among specimens. These data indicate that rapid, homogeneous, and comparatively
      low-temperature heating, such as defocused infrared radiation, controls Ca-P
      solubility and ensures the adherence of the coatings to the substrate.

PMID- 9240386
TI  - The effects of maturity and dehydration shrinkage on resin-modified glass-ionomer
      restorations.
AB  - The dimensional change, including hygroscopic change, of adhesive dental
      materials is a clinically important topic, since excessive changes could cause
      debonding from tooth structure. The water balance of glass-ionomer cements arises
      mainly from their sensitivity to the environment; depending on the surroundings,
      they can gain or lose water, either of which can be potentially damaging. These
      effects become less noticeable as the cement ages. The effects of maturity of the
      newer resin-modified glass-ionomer materials and their responses to changes in
      moisture are unknown. Using confocal microscopy, we examined the effects of
      dehydration stress on the glass-ionomer/tooth interface in specimens of various
      degrees of maturity. Wedge-shaped cervical cavities in extracted teeth were
      restored with one of three resin-modified glass-ionomer restorative materials.
      The control specimens were restored with a conventional glass ionomer. The
      samples were left to mature, then sectioned and examined at 1 day, 1 wk, 1 mo, 3
      mos, 6 mos, and 1 yr. After being sectioned, each specimen was examined
      immediately with a confocal microscope with water-immersion objectives so that
      the subsurface interfacial characteristics could be studied. The specimen was
      then allowed to dehydrate under the microscope, with further examinations at 15,
      30, and 60 min. Generally, gap formation at the interface occurred within 15 min
      of dehydration. All materials showed a different pattern of gap change with
      maturity, probably due to the different setting mechanisms involved. All of them
      were susceptible to dehydration shrinkage up to 3 mos of maturity. At 6 mos and 1
      yr, Fuji II and Fuji II LC showed insensitivity to dehydration. Vitremer and
      Photac-Fil showed less sensitivity to dehydration at 1 yr than at 6 mos. The
      results of this study of the maturing polymerized resin-modified cements have
      potential clinical implications in the handling of these materials; the addition
      of resin has not significantly reduced the glass ionomer's susceptibility to
      dehydration problems.

PMID- 9240387
TI  - Variability in cytotoxicity and fluoride release of resin-modified glass-ionomer
      cements.
AB  - New-generation glass-ionomer cements contain resin to improve their restorative
      properties. These resin-modified glass-ionomer cements vary considerably in their
      chemistry, which could result in corresponding variability in their physical and
      biological properties. This study investigated the cytotoxicity and the fluoride
      release of two resin-modified glass ionomers, a conventional glass-ionomer
      cement, and a resin composite. Samples were prepared and extracted in distilled
      water for 1, 4, and 7 days; eluates were filtered and tested by means of 3T3
      mouse fibroblasts. Cytotoxicity (MTT assay) values were low for all materials and
      extraction times, indicating minimal cytotoxicity of all materials (less than 30%
      inhibition). Cytotoxicity of one resin-modified glass ionomer was significantly
      higher than for the other materials (p < 0.001). One resin-modified glass ionomer
      and the conventional glass-ionomer cement released significantly more fluoride at
      each time interval (p < 0.001) than the other resin-modified glass-ionomer cement
      and the resin composite. Fluoride release and cytotoxicity were correlated (r2 =
      0.60; p < 0.001), although the fluoride release does not account for the
      cytotoxicity observed. Cytotoxicity and fluoride release suggest that one hybrid
      behaved more like a conventional glass ionomer, and the other like a resin
      composite. These differences may have implications for material selection in
      specific clinical situations.

PMID- 9240388
TI  - Wear and marginal breakdown of composites with various degrees of cure.
AB  - Loss of anatomical form due to wear has been cited as one factor limiting the
      clinical use of posterior composites. The physical properties and possibly the
      wear resistance of composite are influenced by the extent to which it is cured.
      The aim of this study was to vary degree of conversion (DC) in composites to test
      the hypothesis that resistance to wear and marginal breakdown could be improved
      by enhanced curing. A light-cured hybrid composite containing a 50% Bis-GMA/50%
      TEGDMA resin and 62 vol% of strontium glass (1 to 2 microm) with microfill silica
      was formulated (Bisco). Composite was placed into two 2.5-mm-diameter cylindrical
      holes in Co-Cr teeth replacing first and second molars in the mandibular dentures
      of 50 edentulous patients. The composites were light-cured for different time
      periods (9 s, 12 s, 25 s, 40 s, and 40 s + 10 min at 120 degrees C) and then
      polished. The microfill Heliomolar was also tested. DC (%) was measured by FTIR
      and ranged between 55% for 9 s of light-curing and 67% for 40 s of light-curing
      followed by heat application. Impressions were evaluated at baseline, 6 mo, 1 yr,
      and 2 yrs. Stone casts were evaluated independently by three observers to
      determine the % of the total margin exhibiting breakdown. Epoxy replicas were
      measured with a profilometer for wear. Wear of the hybrid composite at 2 yrs
      ranged from a high of 144 microm with 9 s of light-curing to a low of 36 microm
      with 40 s of light-curing followed by heat. Heliomolar exhibited from 11 to 16
      microm of wear at 2 yrs. There was a strong negative correlation (r2 = 0.91)
      between the degree of cure and the abrasive wear of the hybrid composites.
      Marginal breakdown was negligible for the hybrids, and was reduced for the
      microfill from 40% to 15% of the margin by heat treatment. This study showed that
      the resistance to abrasive wear of a dental composite could be improved by
      enhancement of its degree of conversion.

PMID- 9240389
TI  - Investing in your future.

PMID- 9240390
TI  - The functional organization of working memory processes within human lateral
      frontal cortex: the contribution of functional neuroimaging.
AB  - Recent functional neuroimaging studies have provided a wealth of new information
      about the likely organization of working memory processes within the human
      lateral frontal cortex. This article seeks to evaluate the results of these
      studies in the context of two contrasting theoretical models of lateral frontal
      lobe function, developed through lesion and electrophysiological recording work
      in non-human primates (Goldman-Rakic, 1994, 1995; Petrides, 1994, 1995). Both
      models focus on a broadly similar distinction between anatomically and
      cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical
      areas, but differ in the precise functions ascribed to those regions. Following a
      review of the relevant anatomical data, the origins of these two theoretical
      positions are considered in some detail and the main predictions arising from
      each are identified. Recent functional neuroimaging studies of working memory
      processes are then critically reviewed in order to assess the extent to which
      they support either, or both, sets of predictions. The results of this meta
      analysis suggest that lateral regions of the frontal lobe are not functionally
      organized according to stimulus modality, as has been widely assumed, but that
      specific regions within the dorsolateral or ventrolateral frontal cortex make
      identical functional contributions to both spatial and non-spatial working
      memory.

PMID- 9240391
TI  - Recovery of ChAT immunoreactivity in axotomized rat cholinergic septal neurons
      despite reduced NGF receptor expression.
AB  - Previous studies have suggested that target-derived nerve growth factor (NGF) is
      essential for the survival of cholinergic basal forebrain neurons. Thus, axotomy
      of septohippocampal neurons in adult rats resulting in the withdrawal of target
      derived NGF caused a dramatic loss of choline acetyltransferase (ChAT)
      immunoreactive neurons in the medial septum-diagonal band complex. We have
      recently shown that this loss of immunolabelled neurons does not indicate cell
      death, since many septohippocampal cholinergic neurons recover their
      immunoreactivity for ChAT after a long survival time despite disconnection from
      target-derived neurotrophins. One possibility would be that these surviving ChAT
      immunoreactive neurons have gained access to other, probably local, NGF sources.
      Here we provide evidence that the recovery of ChAT immunoreactivity after axotomy
      is not accompanied by a similar recovery of NGF receptor expression in these
      neurons. In situ hybridization for p75NTR mRNA and trkA mRNA 6 months after
      bilateral fimbria-fornix transection revealed a substantial loss of labelled
      cells. In addition, there was a persisting loss of p75NTR-immunoreactive and NGF
      immunoreactive medial septal neurons. Cholinergic neurons in controls did not
      express NGF mRNA, but were heavily immunostained for NGF protein due to receptor
      mediated uptake. These data suggest that at least some cholinergic
      septohippocampal neurons re-express ChAT either independently of NGF or with a
      reduced need for NGF.

PMID- 9240392
TI  - Type 2 metabotropic glutamate (mGlu) receptors tonically inhibit transmitter
      release in rat caudate nucleus: in vivo studies with (2S,1'S,2'S,3'R)-2-(2'
      carboxy-3'-phenylcyclopropyl)glycine, a new potent and selective antagonist.
AB  - Anatomical, biochemical and electrophysiological studies have previously shown
      that cortico-striatal terminals contain abundant presynaptic group 2 metabotropic
      glutamate (mGlu) receptors. Using brain slices we have previously shown that
      these receptors inhibit depolarization-induced transmitter release. Using
      microdialysis in freely moving rats, we now report the effects of group 2 mGlu
      receptor agonists and antagonists on glutamate concentration in the caudate
      extracellular fluid. A mild decrease (20-30%) in glutamate concentration in
      caudate dialysates was observed when 1S,3R-1-aminocyclopentane-1,3-dicarboxylic
      acid or (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (L-CCG-1), mGlu receptor
      agonists, was locally administered. On the contrary, alpha-methyl-4
      carboxyphenylglycine, an antagonist of type 1 and type 2 mGlu receptors,
      increased the glutamate concentration in dialysates by up to 3.5-fold, and its
      effects were prevented by the simultaneous administration of L-CCG-1, a
      preferential type 2 mGlu receptor agonist. A significant increase of glutamate
      output in striatal dialysate was also found after local administration of
      (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, another structurally
      unrelated, relatively selective and potent type 2 mGlu receptor antagonist. The
      results suggest that type 2 mGlu receptors tonically inhibit transmitter release
      from cortico-striatal terminals. Since the cortico-striatal pathway profoundly
      affects the function of a large percentage of caudate neurons, it is reasonable
      to predict that the use of selective type 2 mGlu receptor agents will be helpful
      for scientific and therapeutic studies on the physiopathology of basal ganglion
      disorders.

PMID- 9240393
TI  - Noradrenaline modulates glutamate-mediated neurotransmission in the rat
      basolateral amygdala in vitro.
AB  - The entorhinal cortex and the amygdala are interconnected structures of the
      limbic system in which paroxysmal activity occurs during temporal lobe epilepsy.
      Conflicting evidence shows that noradrenaline (i) inhibits the spreading to other
      parts of the limbic system of paroxysmal activity generated in the amygdala or
      the entorhinal cortex, but also (ii) increases glutamatergic transmission in the
      basolateral amygdala. Given our previous work on the inhibitory effect of
      noradrenaline on entorhinal cortex neurons, we developed an in vitro slice
      preparation to study the synaptic transmission in the basolateral amygdala and
      its modulation by noradrenaline. Noradrenaline reduced the fast excitatory
      postsynaptic potential (EPSP) by approximately 40% at 100 microM and the slow
      EPSP by approximately 50% at 50 microM. A similar effect was obtained with the
      alpha2-agonist UK 14304 at 100 and 50 microM respectively. In contrast, the beta
      agonist isoproterenol increased the fast EPSP by approximately 40% at 100 microM
      and the slow EPSP by approximately 20% at 50 microM. Accordingly, the effect of
      noradrenaline on the EPSPs was blocked by the alpha2-antagonist yohimbine (10
      microM) but not by the alpha1-antagonist prazosine (10 microM) and the beta
      antagonist propranolol (10 microM). Noradrenaline (50-100 microM) was ineffective
      on most (14/16) of the isolated inhibitory postsynaptic potentials (IPSPs). These
      experiments provide evidence that noradrenaline inhibits the excitatory synaptic
      response of basolateral amygdala neurons. A pharmacological analysis revealed
      that the noradrenergic modulation of the excitatory transmission in the
      basolateral amygdala can be dissected into a predominant alpha2-adrenoreceptor
      mediated inhibition and a beta-adrenoreceptor-mediated excitation.

PMID- 9240394
TI  - How reliably does a neuron in the visual motion pathway of the fly encode
      behaviourally relevant information?
AB  - How reliably neurons convey information depends on the extent to which their
      activity is affected by stochastic processes which are omnipresent in the nervous
      system. The functional consequences of neuronal noise can only be assessed if the
      latter is related to the response components that are induced in a normal
      behavioural situation. In the present study the reliability of neural coding was
      investigated for an identified neuron in the pathway processing visual motion
      information of the fly (Lucilia cuprina). The stimuli used to investigate the
      neuronal performance were not exclusively defined by the experimenter. Instead,
      they were generated by the fly itself, i.e. by its own actions and reactions in a
      behavioural closed-loop experiment, and subsequently replayed to the animal while
      the activity of an identified motion-sensitive neuron was recorded. Although the
      time course of the neuronal responses is time-locked to the stimulus, individual
      response traces differ slightly from each other due to stochastic fluctuations in
      the timing and number of action potentials. Individual responses thus consist of
      a stimulus-induced and a stochastic response component. The stimulus-induced
      response component can be recovered most reliably from noisy neuronal signals if
      these are smoothed by intermediate-sized time windows (40-100 ms). At this time
      scale the best compromise is achieved between smoothing out the noise and
      maintaining the temporal resolution of the stimulus-induced response component.
      Consequently, in the visual motion pathway of the fly, behaviourally relevant
      motion stimuli can be resolved best at a time scale where the timing of
      individual spikes does not matter.

PMID- 9240395
TI  - Modulation of responses of four types of feline ascending tract neurons by
      serotonin and noradrenaline.
AB  - Modulation of responses of four types of ascending tract cells by noradrenaline
      and serotonin was compared in order to investigate how information forwarded by
      these cells may be gated by monoaminergic tract neurons. Spinocervical tract,
      postsynaptic dorsal column and dorsal spinocerebellar tract neurons located in
      Clarke's column and in the dorsal horn were identified by their axonal
      projections. Noradrenaline and serotonin were applied ionophoretically close to a
      selected neuron, and their effects were tested on extracellularly recorded
      responses of this neuron to electrical stimulation of low-threshold skin
      afferents and group II muscle spindle afferents. The modulatory actions of
      noradrenaline and serotonin were estimated from changes in the number of
      responses evoked by 30 successive stimuli, the minimal latencies of these
      responses, and their firing frequency. All four populations of ascending tract
      neurons investigated were modulated by serotonin and noradrenaline, but not in
      the same way. The responses were most often depressed by noradrenaline and
      facilitated by serotonin, but in some types of neuron they were affected in the
      same direction. Transmission from low-threshold skin and group II muscle
      afferents changed in the same direction in some types of neuron but in the
      opposite direction in other types. The results indicate that transfer of
      information from skin and group II muscle afferents to supraspinal centres may be
      gated by descending monoaminergic pathways in a highly differentiated manner, and
      is adjusted to the requirements of various behavioural situations.

PMID- 9240396
TI  - Neurotrophin-3 delivered locally via fibronectin mats enhances peripheral nerve
      regeneration.
AB  - A better understanding of the mechanisms of nerve regeneration could improve the
      outcome of surgical nerve repair. We have previously shown that axonal
      regeneration is increased by nerve growth factor. Neurotrophin-3 (NT-3) belongs
      to the same family as nerve growth factor but acts on a distinct neuron
      subpopulation. As little is known about its role following nerve injury, we have
      investigated the effect of NT-3 delivered via fibronectin mats, previously shown
      to support nerve regeneration comparable to nerve grafts. NT-3 stimulation (0.1
      1000 ng/ml) of neurite extension from embryonic chick dorsal root ganglia in
      vitro has shown that fibronectin can bind and release bioactive NT-3. Fibronectin
      mats impregnated with NT-3 (500 ng/ml) were grafted into 1 cm sciatic nerve
      defects in adult Lewis rats. Plain mats were used as controls. Computerized
      quantification of penetration distance, volume of axonal regeneration and
      myelinated fibre counts was undertaken using immunostaining for axonal markers
      (growth-associated protein 43, calcitonin gene-related peptide, substance P,
      vasoactive intestinal peptide and neuropeptide tyrosine), or S100 or thionine
      blue staining up to 8 months postoperatively. The maximal effect of NT-3 occurred
      at day 15, when for GAP43-immunostained axons both penetration distance (NT-3,
      6.10 +/- 0.42 mm; control, 4.11 +/- 0.41 mm; P < 0.01) and staining area (NT-3,
      0.137 +/- 0.012 mm2; control, 0.077 +/- 0.018 mm2; P < 0.05) were significantly
      increased. Similar results were found for each neuronal subpopulation
      investigated. By 8 months after repair, the NT-3 group supported a significantly
      greater number of myelinated axons (NT-3, 7003 +/- 402; control, 4932 +/- 725; P
      < 0.05) of similar diameter and g-ratio to controls. These results demonstrate
      the contribution of NT-3 to the increase of nerve regeneration promoted by growth
      factors.

PMID- 9240397
TI  - GABA- and glutamate-evoked responses in the rat ventral pallidum are modulated by
      dopamine.
AB  - Microiontophoresis was used to investigate the influence of dopamine on GABA- and
      glutamate-induced responses from ventral pallidal neurons recorded
      extracellularly in chloral hydrate-anaesthetized rats. Modulation was determined
      by comparing dopamine-induced alterations in amino acid-induced activity
      ('signal') with dopamine-induced effects on spontaneous firing ('noise'). A
      dopamine ejection current-response curve was generated to determine the current
      levels that did not alter spontaneous firing ('subthreshold') and those that
      produced approximately 50% of the maximal dopamine-induced response (ECur50). Co
      iontophoresis of dopamine with GABA generally diminished the inhibitory influence
      of GABA on pallidal neuron firing; 70% of neurons tested with ECur50 dopamine
      demonstrated a decrease in the signal-to-noise ratio whereas 10% displayed an
      increase. At subthreshold dopamine ejection currents, 59% of neurons responded
      with a decrease and 18% responded with an increase in the GABA signal-to-noise
      ratio. When ECur50 dopamine was co-iontophoresed with glutamate, 84% of the
      neurons displayed a decrease in the signal-to-noise ratio for glutamate-evoked
      excitations whereas 11% demonstrated an increase. Subthreshold dopamine ejection
      currents decreased the signal-to-noise ratio in 62% of the ventral pallidal
      neurons excited by glutamate and increased the ratio in 23%. These data
      illustrate that dopamine substantially alters GABA- and glutamate-evoked
      responses even at ejection currents that are below those necessary to change
      spontaneous firing. Thus, it appears that neuromodulation is an important means
      by which dopamine influences ventral pallidal neuronal activity.

PMID- 9240398
TI  - Subthalamic ablation reverses changes in basal ganglia oxidative metabolism and
      motor response to apomorphine induced by nigrostriatal lesion in rats.
AB  - In Parkinson's disease, the functional architecture of the basal ganglia nuclei
      undergoes profound alterations, one of the most important of which is
      overactivity of the basal ganglia output nuclei. This phenomenon seems to be
      intimately related to pathological overactivity of the subthalamic nucleus, which
      directly modulates the basal ganglia output through its glutamatergic
      projections. In this study, we investigated the effects of unilateral subthalamic
      nucleus lesions on the activities of succinate dehydrogenase and cytochrome
      oxidase, two markers of neuronal activity, in rats with prior unilateral lesions
      of the nigrostriatal tract. We also explored the effect of subthalamic nucleus
      lesions on the rotational response to systemic apomorphine. Rats with unilateral
      lesions of the nigrostriatal tract showed ipsilateral increases in enzyme
      activity in the basal ganglia output nuclei, entopeduncular nucleus and
      substantia nigra pars reticulata. Selective subthalamic nucleus destruction
      completely reversed this phenomenon. In addition, subthalamic nucleus lesions
      abolished the rotational response to apomorphine. These results confirm that
      overactivity of the subthalamic nucleus plays a pivotal role in the functional
      alterations of basal ganglia associated with Parkinson's disease. They also shed
      further light on the neural mechanisms through which manipulations of subthalamic
      activity can ameliorate Parkinson's disease symptoms.

PMID- 9240399
TI  - Diffusion in axon guidance.
AB  - Axon guidance by target-derived diffusible factors plays an important role in the
      development of the nervous system. This paper considers the constraints imposed
      on this process by the mathematics of diffusion. A point source continuously
      producing a factor into an infinite three-dimensional volume is considered as a
      model for both the in vivo and in vitro situation. Basic constraints for
      effective guidance are assumed to be that the concentration falls between certain
      maximum and minimum limits, and that the percentage change in concentration
      across the width of the growth cone exceeds a certain minimum value. The
      evolution of the shape of the gradient over time is analysed. Using biologically
      reasonable parameter values, it is shown that the maximum range over which growth
      cone guidance by a diffusible factor is possible for large times (several days)
      after the start of the production of the factor is 500-1000 microm. This maximum
      distance is independent of the diffusion constant of the diffusing molecule,
      applies to both chemoattractants and chemorepellents, and agrees with
      experimental data. At earlier times, however, the constraints may be satisfied
      for distances up to several millimetres. The time it takes for this maximum
      guidance distance to fall to the asymptotic value depends on the diffusion
      constant. This time is a few hours for a small molecule but as much as a few days
      for a large molecule. The model therefore predicts that guidance over distances
      larger than 1000 microm is possible if the start of production of the factor is
      carefully matched to the time when guidance is required.

PMID- 9240400
TI  - Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental
      spinal cord injury in mouse: an in situ hybridization study.
AB  - Injury to the spinal cord induces a complex cascade of cellular reactions at the
      local lesion area: secondary cell death and inflammatory reactions as well as
      scar and cavity formation take place. In order to investigate the molecular
      features underlying this local wounding response and to determine their
      pathophysiological implications, we studied the expression pattern of pro
      inflammatory and chemoattractant cytokines in an experimental spinal cord injury
      model in mouse. We show by in situ hybridization that transcripts for the pro
      inflammatory cytokines TNF alpha and IL-1 as well as the chemokines MIP-1alpha
      and MIP-1beta are upregulated within the first hour following injury. In this
      early phase, the expression of the pro-inflammatory cytokines is restricted to
      cells in the surroundings of the lesion area probably resident CNS cells. While
      TNF alpha is expressed in a very narrow time window, IL-1 can be detected in a
      second phase in a subset of polymorphonuclear granulocytes which immigrate into
      the spinal cord around 6 h. Message for the chemokines MIP-1alpha and beta is
      expressed in a generalized way in the grey matter of the entire spinal cord
      around 24 h and gets again restricted to the cellular infiltrate at the lesion
      site at 4 days following injury. Interestingly, our data suggest that resident
      CNS cells, most probably microglial cells, and not peripheral inflammatory cells,
      are the main source for cytokine and chemokine mRNAs. The defined cytokine
      pattern observed indicates that the inflammatory events upon lesioning the CNS
      are tightly controlled. The very early expression of pro-inflammatory cytokine
      and chemokine messages may represent an important element of the recruitment of
      inflammatory cells. Additional pathophysiological consequences of the specific
      cytokine pattern observed remain to be determined.

PMID- 9240401
TI  - NMDA receptor properties in rat supraoptic magnocellular neurons:
      characterization and postnatal development.
AB  - Hypothalamo-neurohypophysial magnocellular neurons display specific electrical
      activities in relation to the mode of release of their hormonal content
      (vasopressin or oxytocin). These activities are under strong glutamatergic
      excitatory control. The implication of NMDA receptors in the control of
      vasopressinergic and oxytocinergic neurons is still a matter of debate. We here
      report the first detailed characterization of functional properties of NMDA
      receptors in voltage-clamped magnocellular neurons acutely dissociated from the
      supraoptic nucleus. All cells responded to NMDA with currents that reversed
      polarity around 0 mV and were inhibited by D-2-amino-5-phosphonovalerate (D-APV)
      and by 100 microM extracellular Mg2+ (at -80 mV). Sensitivity to the co-agonist
      glycine (EC50, 2 microM) was low compared with most other neuronal preparations.
      The receptors displayed low sensitivity to ifenprodil, were insensitive to
      glycine-independent potentiation by spermine, and had a unitary conductance of 50
      pS. No evidence was found for two distinct cell populations, suggesting that
      oxytocinergic and vasopressinergic neurons express similar NMDA receptors.
      Characterization of NMDA receptors at different postnatal ages revealed a
      transient increase in density of NMDA currents during the second postnatal week.
      This was accompanied by a specific decrease in sensitivity to D-APV, with no
      change in NMDA sensitivity or any other properties studied. Supraoptic NMDA
      receptors thus present characteristics that strikingly resemble those of
      reconstituted receptors composed of NR1 and NR2A subunits. Understanding the
      functional significance of the development of NMDA receptors in the supraoptic
      nucleus will require further knowledge about the maturation of neuronal
      excitability, synaptic connections and neurohormone release mechanisms.

PMID- 9240402
TI  - Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha
      after sciatic nerve lesion in the mouse.
AB  - Glial cell line-derived neurotrophic factor (GDNF), first characterized for its
      effect on dopamine uptake in central dopaminergic neurons, appears to be a
      powerful neurotrophic factor for motor neurons. GDNF has recently been shown to
      signal through a multisubunit receptor. This receptor is composed of a ligand
      binding subunit, called GDNF receptor alpha (GDNFR alpha), and a signalling
      tyrosine kinase subunit, Ret. To gain further insight into GDNF function, we
      investigated the expression of GDNF and its receptors after nerve lesion in adult
      mice. Analysis of expression in muscle, nerve and spinal cord by RNase protection
      assay and in situ hydridization revealed that, in adult non-lesioned mice, GDNF
      mRNA was expressed in the nerve and GDNFR alpha mRNA in the nerve and the spinal
      cord, while the expression of Ret was restricted to spinal cord motor neurons.
      After a sciatic nerve crush a rapid increase in GDNF mRNA was observed in the
      distal part of the nerve and a delayed elevation in the muscle, while GDNFR alpha
      mRNA was up-regulated in the distal part of the sciatic nerve but not in proximal
      nerve or spinal cord. The lesion also induced a rapid increase in Ret mRNA
      expression, but the increase was observed only in spinal cord motor neurons and
      in dorsal root ganglion neurons. A pattern of expression of GDNF and its
      receptors similar to that seen after lesion in the adult was detected during
      embryonic development. Administration of GDNF enhanced sciatic nerve regeneration
      measured by the nerve pinch test. Taken together, these results suggest that GDNF
      has an important role during regeneration after nerve damage in the adult.

PMID- 9240403
TI  - Influence of interleukin-6 on neural activity and transcription of the gene
      encoding corticotrophin-releasing factor in the rat brain: an effect depending
      upon the route of administration.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine produced by various lymphoid and
      neural cells. In addition to its classic role during immune and inflammatory
      responses, IL-6 acts on the central nervous system to elicit changes, such as
      activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study
      investigated the effects of systemic and central injection of IL-6 on neural
      activity and transcription of the corticotrophin-releasing factor (CRF) gene in
      the brain of conscious rats. The animals were killed 1 and 3 h after a single
      infusion of IL-6 into the right jugular vein (0.83 or 3.0 microg) or the right
      lateral ventricle (0.2 microg) and their brains cut from the olfactory bulb to
      the end of the medulla in 30-microm coronal sections. Messenger RNA encoding the
      protein Fos, a marker of neural activity, and the neuropeptide CRF were localized
      by in situ hybridization histochemistry using 35S-labelled exonic and intronic
      riboprobes. The results show that systemic injection of IL-6 induced specific
      transcription of c-fos gene in most of the sensorial circumventricular organs,
      including the organum vasculosum lamina terminalis, subfornical organ, median
      eminence, and area postrema, as well as in the central nucleus of the amygdala
      and bed nucleus of the stria terminalis. On the other hand, central injection of
      IL-6 increased cellular level of c-fos mRNA in the ependymal layer and the walls
      of the ventricles, meninges, nucleus of the solitary tract, and circumventricular
      organs. These effects were rapid and transient, since the signals for c-fos mRNA
      were detected 1 h after both treatments and vanished 3 h afterwards. Moreover,
      the CRF gene was not activated by either systemic or central administration of IL
      6 in the paraventricular nucleus of the hypothalamus. Taken together, these
      results suggest that circumventricular organs hold a privileged position in
      mediating the central effects of systemic IL-6 and that centrally injected IL-6
      can strongly activate cells of the ventricular system and surrounding structures.
      Although this differential circuitry may explain distinct origin-dependent
      functions of IL-6, this cytokine seems insufficient, in itself, to induce
      transcription of the gene encoding neuroendocrine CRF, the neuropeptide
      responsible for control of the HPA axis.

PMID- 9240404
TI  - Voltage oscillations in Xenopus spinal cord neurons: developmental onset and
      dependence on co-activation of NMDA and 5HT receptors.
AB  - The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated
      voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine
      (5HT) receptors was explored in motor neurons of late embryonic and early larval
      Xenopus laevis. Under tetrodotoxin, 100 microM NMDA elicited a membrane
      depolarization of around 20 mV, but did not lead to voltage oscillations.
      However, following the addition of 2-5 microM 5HT, oscillations were observed in
      12% of embryonic and 70% of larval motor neurons. The voltage oscillations
      depended upon co-activation of NMDA and 5HT receptors since they were curtailed
      by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid
      (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the
      absence of NMDA also failed to elicit oscillations. Oscillations could be induced
      by the non-selective 5HT1alpha receptor agonist, 5-carboxamidotryptamine (5CT)
      and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT1, a
      selective 5HT1alpha receptor antagonist. To test whether 5HT enables voltage
      oscillations by modulating the voltage-dependent block of NMDA channels by Mg2+,
      membrane conductance was monitored under tetrodotoxin. Although 5HT caused
      membrane hyperpolarization of 4-8 mV, there was little detectable change in
      conductance. NMDA application caused an approximate 20 mV depolarization and an
      'apparent' decrease in conductance, presumably due to the conductance pulse
      bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore.
      5HT further decreased conductance, which we propose is due to its enhancement of
      the voltage-dependent Mg2+ block. When the membrane potential was depolarized by
      approximately 20 mV via depolarizing current injection (to mimic the NMDA-induced
      depolarization), 5HT increased rather than decreased membrane conductance.
      Furthermore, 5HT did not affect the increase in membrane conductance following
      NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA
      receptor-mediated voltage oscillations develop in a brief period after hatching,
      and that they depend upon the co-activation of 5HT and NMDA receptors. The
      enabling function of 5HT may involve the facilitation of the voltage-dependent
      block of the NMDA ionophore by Mg2+ through activation of receptors with
      5HT1alpha-like pharmacology.

PMID- 9240405
TI  - Evidence for neurotensin autoreceptors and relationship of neurotensin and its
      receptors with tyrosine hydroxylase-positive neurons in rat primary hypothalamic
      cultures.
AB  - Neurotensin is present in high quantity in the hypothalamus, where it regulates
      pituitary hormone secretion. A relationship between dopaminergic and
      neurotensinergic systems has been suggested in the hypothalamus in studies
      showing an effect of neurotensin on tuberoinfundibular dopaminergic neurons. In
      order to determine the anatomical basis of such interactions, primary cultures of
      rat hypothalamic neurons were used. Tyrosine hydroxylase and neurotensin
      containing cells were identified by immunocytochemistry and neurotensin binding
      sites by [125I]Tyr3-neurotensin autoradiography. Colocalization studies showed
      that neurotensin immunoreactivity was present in 16% of tyrosine hydroxylase
      positive cells, and that these neurotensin/tyrosine hydroxylase neurons
      represented more than half (58%) of the neurotensinergic population. Five percent
      of the tyrosine hydroxylase-positive cells had neurotensin binding sites,
      suggesting that only a restricted number of hypothalamic dopaminergic neurons is
      responsive to neurotensin. Neurotensin binding sites were also found on some
      neurotensin-positive cells, demonstrating for the first time the presence of
      autoreceptors for this peptide on neurons. These results in primary cultures
      provide a cellular basis for direct effects of neurotensin on a subpopulation of
      hypothalamic dopaminergic cells, and support the possibility of an autocrine
      action of neurotensin in the hypothalamus.

PMID- 9240406
TI  - Peroxynitrite and nitric oxide donors induce neuronal apoptosis by eliciting
      autocrine excitotoxicity.
AB  - Endogenous generation of nitric oxide and its congeners, including peroxynitrite
      (ONOO-), has been implicated in the mechanism of neuron loss in neurodegenerative
      diseases. Accordingly, nitric oxide donors and ONOO- can elicit both apoptosis
      and necrosis in neuron cultures. Here we show that nitric oxide donors and ONOO-
      are each able to trigger apoptosis of mouse cerebellar granule cells by an
      excitotoxic mechanism requiring exocytosis and NMDA receptor-mediated
      intracellular Ca2+ overload. This conclusion is supported by the following
      findings. Apoptosis was induced by various nitric oxide donors or by direct
      addition of ONOO- to differentiated cerebellar granule cell cultures that were
      sensitive to NMDA toxicity, but not in cerebellar granule cells that did not
      display NMDA-induced cell death (i.e. early days in culture) or in various glial
      cell populations. Donors of ONOO- or nitric oxide stimulated a sustained increase
      in intracellular Ca2+, which was prevented by inhibitors of NMDA receptors, such
      as MK-801 and 5-phospho-aminovaleric acid, or by dampening neuronal electrical
      activity with high concentrations of extracellular Mg2+. Moreover, these
      treatments and the exposure of cerebellar granule cells in nominally Ca2+-free
      media prevented apoptotic cell death. Both the intracellular Ca2+ increase and
      apoptosis elicited by ONOO- or the nitric oxide donors were prevented by blocking
      exocytosis with tetanus toxin or botulinum neurotoxin C.

PMID- 9240407
TI  - Organization and development of facial motor neurons in the kreisler mutant
      mouse.
AB  - The adult facial nerve contains the axons from two populations of efferent
      neurons. First, the branchiomotor efferent neurons that innervate the muscles of
      the second arch. These neurons project out of the hindbrain in the motor root and
      form the facial motor nuclei. Second, the preganglionic efferent neurons that
      innervate the submandibular and pterygopalatine ganglia. These neurons project
      from the hindbrain via the intermediate nerve and form the superior salivatory
      nucleus. The motor neurons of the facial nerve are known to originate within
      rhombomeres 4 and 5. In the kreisler mouse mutant there is a specific disruption
      of the hindbrain rhombomeres 5 and 6 appear to be absent. To investigate changes
      in the organization of the facial motor neurons in this mutant, we have used
      lipophilic dyes to trace the facial motor components both retrogradely and
      anterogradely. As expected, facial motor neurons are missing from rhombomere 5 in
      this mutant. In addition, the loss of these neurons correlates with the specific
      loss of the superior salivatory nucleus. In contrast, the branchiomeric neurons,
      that originate in rhombomere 4, appear to develop normally. This includes the
      caudal migration of their cell bodies forming the genu of the facial nerve. Our
      studies confirm that rhombomeres are critical to hindbrain development and that
      they are the fundamental unit at which motor neurons are specified.

PMID- 9240408
TI  - Modulation of sensory and excitatory amino acid responses by nitric oxide donors
      and glutathione in the ventrobasal thalamus of the rat.
AB  - Nitric oxide has been identified as having a role in synaptic transmission in the
      central nervous system. In the ventrobasal complex of the thalamus (VB), the
      precursor of nitric oxide synthesis, L-arginine, causes enhancement of excitatory
      amino acid responses and somatosensory transmission. In this study, the nitric
      oxide donors sodium nitroprusside, 3-morpholinosydnonimine and S
      nitrosoglutathione were applied to VB relay neurons by iontophoresis and
      responses of single neurons were recorded extracellularly. Sodium nitroprusside
      caused selective inhibition of responses to NMDA, probably mediated by a by
      product, ferrocyanide, as described in previous studies. 3-Morpholinosydnonimine
      and S-nitrosoglutathione, however, caused potentiation of responses to sensory
      stimuli and to excitatory amino acids. In contrast, glutathione in both its
      reduced and oxidized forms reduced such responses, and this suggests that the
      potentiating effect of S-nitrosoglutathione could be due to nitric oxide
      production. These results are consistent with the hypothesis that nitric oxide
      may have a local modulatory role in the thalamus. Data are presented which
      suggest that glutathione may have a negative modulatory influence on
      neurotransmission and excitatory amino acid responses in the ventrobasal
      thalamus.

PMID- 9240409
TI  - Metabotropic glutamate receptors in the rat nucleus accumbens.
AB  - The effects of glutamate metabotropic receptors (mGluRs) on excitatory
      transmission in the nucleus accumbens were investigated using
      electrophysiological techniques in rat nucleus accumbens slices. The broad
      spectrum mGluR agonist (1S,3R)-1-aminocyclopentyl-1,3-dicarboxylate, the mGluR
      group 2 selective agonists (S)-4-carboxy-3-hydroxyphenylglycine, (1S,3S)-ACPD)
      and (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1), and the mGluR group 3
      specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) all reversibly inhibited
      evoked excitatory synaptic responses. The specific group 1 mGluR agonist (R,S)
      3,5-dihydroxyphenylglycine [(R,S)-DHPG] did not depress transmission. Dose
      response curves showed that the rank order of agonist potencies was: L-CCG1 > L
      AP4 > (1S,3S)-ACPD. Group 2 and 3 mGluRs inhibited transmission via a presynaptic
      mechanism, as they increased paired-pulse facilitation, decreased the frequency
      of miniature excitatory postsynaptic currents and had no effect on their
      amplitude. The mGluRs did not inhibit transmitter release by reducing voltage
      dependent Ca2+ currents through N- or P-type Ca2+ channels, as inhibition
      persisted in the presence of omega-conotoxin-GVIA or omega-Aga-IVA. The
      depression induced by mGluRs was not affected by specific antagonists of dopamine
      D1, GABA-B or adenosine A1 receptors, indicating direct effects. Finally, (R,S)
      DHPG specifically blocked the postsynaptic afterhyperpolarization current
      (I(AHP)). Our results represent the first direct demonstration of functional
      mGluRs in the nucleus accumbens of the rat.

PMID- 9240410
TI  - Temporo-frontal disconnection impairs visual-visual paired association learning
      but not configural learning in Macaca monkeys.
AB  - Cynomolgus monkeys were tested in two computer-controlled visual associative
      memory tasks. The monkeys chose between visual objects on a screen by touching
      one. In the configural learning task one correct object and one wrong object were
      presented in each trial. Each of these two objects was composed of two coloured
      alphanumeric characters abutted together. The designation of the objects as
      'correct' or 'wrong' followed a configural rule: e.g. if AB and CD are correct
      objects then AD and CB are wrong. In the paired association learning task in each
      trial three spatially separate objects (single alphanumeric characters) were
      presented. The central object was an instruction cue and the designation of the
      side objects as 'correct' or 'wrong' choices followed a paired association rule:
      e.g. if A, C and B are presented (C in the centre) then A is correct and B is
      wrong; however, if A, D and C are presented then C is correct and A is wrong.
      Disrupting the direct cortico-cortical interaction between the inferior temporal
      cortex and the prefrontal cortex by uncinate fascicle transection led to a
      learning deficit in the paired association task but not in the configural task.
      These results suggest that the uncinate fascicle facilitates visual-visual
      associative learning only in the specific case where a visual object acts as an
      instruction cue to guide the conditional choice of another, spatially separate
      object, and they support the evidence for a specific role of the uncinate
      fascicle in the learning of conditional tasks with visual instruction cues.

PMID- 9240411
TI  - Neurons in the rat occipital cortex co-expressing the substance P-receptor and
      GABA: a comparison between in vivo and organotypic cultures.
AB  - The morphology and the distribution of neurons expressing the NK1-receptor (NK1R)
      and the co-expression of gamma-aminobutyric acid (GABA) in these neurons were
      studied in the rat occipital cortex and in organotypic cultures (OTCs) derived
      from this structure. By employing immunohistochemistry, we demonstrate that the
      NK1R-expressing neurons are non-pyramidal neurons and co-express GABA. Some
      differences were noted between in vivo and OTCs. NK1R-expressing neurons in OTCs
      had larger somata and longer dendrites and the proportion stained with an anti
      GABA-antibody (approximately 50%) was smaller than in vivo (90%). The
      preferential location of NK1R-expressing neurons in layers II/III and VI, seen in
      vivo is not present in OTCs where these neurons distribute rather homogeneously
      through layers II-VI. Our findings imply that in contrast to the cat and monkey,
      in the rat occipital cortex the effects of substance P are almost exclusively
      mediated via inhibitory interneurons.

PMID- 9240412
TI  - Evidence that blue-on cells are part of the third geniculocortical pathway in
      primates.
AB  - Colour vision in primates is mediated by cone opponent ganglion cells in the
      retina, whose axons project to the dorsal lateral geniculate nucleus in the
      visual thalamus. It has long been assumed that cone opponent ganglion cells
      project to the parvocellular layers of the geniculate. Here, we examine the role
      of a third subdivision of the geniculocortical pathway: the interlaminar or
      koniocellular geniculate relay cells. We made extracellular recordings in the
      dorsal lateral geniculate nucleus of the common marmoset Callithrix jacchus, a
      New World monkey in which the interlaminar cells are well segregated from the
      parvocellular layers. We found that one group of colour opponent cells, the blue
      on cells, was largely segregated to the interlaminar zone. This segregation was
      common to dichromatic ('red-green colour-blind') and trichromatic marmosets. The
      result calls into question the traditional notion that all colour information
      passes through the parvocellular division of the retino-geniculo-cortical pathway
      in primates.

PMID- 9240413
TI  - Differential display reveals transcriptional up-regulation of the motor molecules
      for both anterograde and retrograde axonal transport during nerve regeneration.
AB  - RNA fingerprinting using an arbitrary primed polymerase chain reaction was
      carried out to compare differences in expression of mRNAs between axotomized and
      normal hypoglossal motoneurons in the mouse. In this survey, the kinesin light
      chain (KLC) was identified as a nerve injury-associated molecule. This was also
      confirmed by in situ hybridization using hemihypoglossal nerve-transected brain
      sections. In order to identify the exact species of molecules belonging to the
      KLC family, in situ hybridization was carried out with oligonucleotide probes
      specific to rat KLC A, KLC B and KLC C, using the rat hypoglossal nerve injury
      model. In addition, expression of both ubiquitous and neuron-specific kinesin
      heavy chain and cytoplasmic dynein which is a retrograde motor, was also
      examined. Expression of all the members of the KLC (A-C) family and dynein was up
      regulated during nerve regeneration, whereas the abundant expression of the
      neuron-specific KHC mRNA was not changed. The present results indicate that the
      molecules associated with both anterograde and retrograde axonal transport are up
      regulated in their expression during efferent motor nerve regeneration,
      suggesting that the retrograde transport of growth factors and anterograde
      transport of vesicles, providing membrane material, could be increased during
      motor nerve regeneration.

PMID- 9240415
TI  - Towards a molecular definition of keratinocyte activation after acute injury to
      stratified epithelia.
AB  - While in recent years we have come to increasingly appreciate the multifaceted
      role of skin, probably none of these novel contributions is as vital as its
      barrier function, inferred centuries ago. In human skin this function is
      fulfilled nearly entirely by the epidermis, a thin stratified squamous epithelium
      made up primarily of keratinocytes and located at the skin surface. Disruption of
      the integrity of epidermis triggers a homeostatic response involving blood
      derived elements and resident skin cell types that is designed to rapidly restore
      a functional epithelial lining over the wound site. This article is focused on
      the process of recruitment of keratinocytes from intact skin tissue at the
      proximal wound edges to participate in re-epithelialization.

PMID- 9240414
TI  - The copper chelator d-penicillamine delays onset of disease and extends survival
      in a transgenic mouse model of familial amyotrophic lateral sclerosis.
AB  - A subpopulation of familial cases of amyotrophic lateral sclerosis has been
      linked to mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). There
      is in vitro evidence that certain SOD1 mutants, in addition to their normal
      dismutation function, show increased ability of the enzyme to act as a
      peroxidase. This reaction is sensitive to inhibition by copper chelators. To test
      this hypothesis in vivo, we administered the copper chelator d-penicillamine to a
      transgenic mouse model of familial amyotrophic lateral sclerosis overexpressing a
      mutated form of human SOD1. We demonstrate that oral administration of d
      penicillamine is able to delay the onset of the disease and extend the survival
      of these mice. Histological studies also showed a decreased loss of facial motor
      neurons in d-penicillamine-treated transgenic mice, corroborating the slower
      evolution of the disease in these animals. These results suggest that copper
      chelators may benefit patients with familial amyotrophic lateral sclerosis linked
      to mutations in the SOD1 gene.

PMID- 9240416
TI  - Differential involvement of synaptic vesicle and presynaptic plasma membrane
      proteins in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by progressive cognitive decline.
      Recent studies have shown that synaptic loss in the cortex is the major correlate
      of cognitive decline in AD. In the present study we assessed synaptic proteins
      such as synaptobrevin, synaptophysin, synaptotagmin, synaptosomal-associated
      protein 25 (SNAP-25), and syntaxin1/HPC-1 in control and AD brains to determine
      whether synaptic proteins are equally or differentially affected in AD. Western
      analysis showed that in AD levels of synaptobrevin and synaptophysin were
      decreased by some 30% from amounts in controls, while those of synaptotagmin,
      SNAP-25, and syntaxin 1/HPC-1 were decreased by only about 10%. As synaptobrevin
      and synaptophysin are localized mainly in transmitter-containing synaptic
      vesicles while SNAP-25 and syntaxin 1/HPC-1 are found in presynaptic plasma
      membranes, these results suggest differential involvement of synaptic components
      in AD.

PMID- 9240417
TI  - Phosphorylation-sensitive secondary structure in a synthetic peptide
      corresponding to the activation loop of MAP kinase.
AB  - A 26-amino acid long synthetic peptide corresponding to the activation loop of
      Xenopus MAP kinase (MAPK), termed IDA (Inter-DFG-APE) MAPK peptide, was found to
      efficiently inhibit the immunoprecipitation of the enzyme with anti-IDA MAPK
      serum. The value of half-inhibition concentration (100 nM) indicates that the IDA
      peptide and native MAPK activation loop are virtually indistinguishable in terms
      of antibody recognition. On the other hand, the Tyr-phosphorylated form of the
      peptide exerted its inhibitory action at around one order higher concentration.
      Shorter nonapeptides covering the epitope sequence of anti-IDA MAPK antibody
      could also affect the immunoprecipitation but at much higher concentrations (half
      inhibition concentration approximately 100 microM) and independently of their
      phosphorylation state. Circular dichroic study revealed that a secondary
      structure could be readily induced with the aid of trifluoroethanol in the
      unphosphorylated and, to a less extent, in the Tyr-phosphorylated IDA MAPK
      peptide but not in the shorter nonapeptides. These results suggest that the
      secondary structure similar to that of the unphosphorylated activation loop of
      MAPK can be formed in the IDA MAPK peptide and may be lost upon its Tyr
      phosphorylation.

PMID- 9240419
TI  - Does the epsilon sequence of phage T7 function as an initiator for the
      translation of CAT mRNA in Escherichia coli?
AB  - Epsilon (epsilon) sequence [UUAACUUUA, complementary to nucleotides 458-466 of
      the 16S ribosomal RNA (rRNA)] which is naturally occurring at the 5'-untranslated
      leader of phage T7 gene 10 mRNA was originally described as a powerful
      translational enhancer in Escherichia coli. Recent studies with this sequence led
      to controversial conclusions about its translational initiation and enhancing
      capability. In this study different sequence derivatives of epsilon were
      constructed to evaluate its efficiency not only to enhance translation of the
      chloramphenicol acetyltransferase (CAT) mRNA in E. coli, but also to function as
      an independent initiator of translation. It was observed that the epsilon
      sequence in combination with the CAT natural Shine-Dalgarno (SDn) or the SD
      consensus sequences enhanced, as expected, the translation of CAT mRNA. The
      natural epsilon sequence without an SD sequence failed to initiate or enhance the
      translation of CAT mRNA. However, when the complementarity of epsilon to 16S rRNA
      was increased from 9 to 16 nucleotides, epsilon alone (without the SD sequence)
      became an independent translational initiator with an efficiency of about 80%
      that obtained with the SD consensus sequence.

PMID- 9240418
TI  - Frequent somatic mutations of hMSH3 with reference to microsatellite instability
      in hereditary nonpolyposis colorectal cancers.
AB  - hMSH3 is one of the human DNA mismatch repair genes but has not yet been reported
      to be associated with hereditary nonpolyposis colorectal cancer. Recently,
      somatic mutation at a polyadenine tract, i.e., (A)8, in hMSH3 was reported in
      cancers with microsatellite instability (MI). To clarify the tumorigenetic role
      of hMSH3, we screened for somatic mutations at the hMSH3 (A)8 repeat in 29 tumors
      from 23 hereditary nonpolyposis colorectal cancer patients. One or two A
      deletions in the (A)8 repeat were found in 11 (57.9%) of the 19 MI-positive
      tumors but not in 10 MI-negative ones, indicating secondary mutations after
      germline mutations of other mismatch repair genes. Moreover, the MI frequency of
      three or more nucleotide repeats was higher in hMSH3 (A)8-mutated tumor cells
      than in nonmutated ones (p<0.05). These data suggest that a mutation of a
      mismatch repair gene enhances the frequency of another mismatch repair gene
      mutation, such as of hMSH3, resulting in severe MI.

PMID- 9240420
TI  - Correlation between direct binding ability of synthetic T. gondii SAG1 peptides
      to HLA-A2 measured by a sensor for surface plasmon resonance and antigenicity of
      the peptides for T. gondii-infected cell-specific CTL.
AB  - Toxoplasma gondii (T. gondii) -infected B lymphoma cells present T. gondii
      antigens in the context of major histocompatibility complex molecules to T.
      gondii-specific CD8+ cytotoxic T cells (CTL). HLA-A2 molecules of T. gondii
      infected human cells have been shown to be used in presenting T. gondii antigens
      to CD8+ CTL. SAG1, one of the major antigenic molecules of T. gondii, is an
      antigen for T. gondii-specific CTL, and represents a possible basis for vaccines.
      The direct binding of nonamer SAG1 peptides to HLA-A2 was assayed here using an
      automated biosensor system with a sensor for surface plasmon resonance detection.
      The antigenicity of synthetic SAG1 peptides to T. gondii-specific CD8+ CTL also
      was assayed. The present study found a high correlation between the binding
      ability of synthetic SAG1 peptides to HLA-A2 and the antigenicity of peptides to
      T. gondii-infected cell-specific CD8+ CTL.

PMID- 9240421
TI  - Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau
      related pathology.
AB  - Cerebrospinal fluid tau (CSF-tau) levels were quantified in 8 patients with
      frontotemporal dementia (FTD), 6 patients with progressive supranuclear palsy
      (PSP), 3 patients with corticobasal degeneration (CBD), and 6 patients with
      dementia with Lewy bodies (DLB). The CSF-tau levels were significantly increased
      in FTD and DLB, but not in PSP and CBD, compared to that previously reported in
      normal controls. Notably, the CSF-tau level in DLB was as high as that in
      Alzheimer's disease (AD). Our study suggests that tau may accumulate in the CSF
      of patients with certain neurodegenerative diseases other than AD and that
      measurement of CSF-tau may not distinguish AD from DLB.

PMID- 9240422
TI  - Role of (ADP-ribose)n catabolism in DNA repair.
AB  - Poly(ADP-ribose) is a reversible covalent-modifier of chromosomal proteins in
      eukaryotic cells. The function of poly(ADP-ribose) is not clear, although it has
      been suggested to be involved in the regulation of DNA transactions such as
      replication, repair, and transcription. Here we describe a specific competitive
      inhibitor of poly(ADP-ribose) glycohydrolase, a macrocircular ellagitannin
      oenothein B, and a nuclear system prepared from synchronized HeLa S3 cells at mid
      G1 phase that enable us to examine the role of poly(ADP-ribose) catabolism in DNA
      repair. The results suggest that poly(ADP-ribose) is capable of generating ATP by
      the concerted action of poly(ADP-ribose) glycohydrolase and ADP-ribose
      pyrophosphorylase and that this ATP enables repair DNA synthesis.

PMID- 9240423
TI  - Role of the heterotrimeric G proteins in stromal-derived factor-1alpha-induced
      natural killer cell chemotaxis and calcium mobilization.
AB  - The CXC chemokine stromal derived factor-1alpha (SDF-1alpha) induces both the
      chemotaxis and calcium mobilization in IL-2-activated NK (IANK) cells. The
      ability of SDF-1alpha to induce IANK cell chemotaxis is inhibited upon
      incorporating antibodies to the alpha subunit of Go and Gq but not Gi, Gs, or Gz,
      whereas (Ca++)i mobilization is inhibited with anti-Go, [corrected] anti-Gq and
      anti-Gs, but not with any other anti-G proteins examined. Further analysis showed
      that antibody to phospholipase C (PLC)beta but not PLCgamma inhibited SDF-1alpha
      induced (Ca++)i mobilization, suggesting that this signal is mediated by G
      protein coupled receptor and not by tyrosine kinase receptors. Our results are
      the first to show that SDF-1alpha is chemoattractant for NK cells, and that this
      effect is coupled to G proteins.

PMID- 9240424
TI  - Role of gastric mucosal constitutive and inducible nitric oxide synthases in the
      development of stress-induced gastric mucosal lesions in rats.
AB  - Changes in gastric mucosal constitutive NO synthase (cNOS) and inducible NO
      synthase (iNOS) activities with the development of gastric mucosal lesions
      induced by water immersion restraint (WIR) stress were investigated in rats
      pretreated with and without NOS inhibitors. A decrease in cNOS activity and an
      increase in iNOS activity in the gastric mucosa occurred with gastric mucosal
      lesion development. Pretreatment with N(G)-monomethyl L-arginine, a non-selective
      NOS inhibitor, enhanced gastric mucosal lesion development with inhibition of
      gastric mucosal cNOS and iNOS activities, although the inhibited iNOS activity
      was still higher than the normal level. Pretreatment with aminoguanidine, a
      selective iNOS inhibitor, prevented gastric mucosal lesion development with
      inhibition of iNOS activity and maintenance of cNOS activity in the gastric
      mucosa. These results indicate that in WIR-stressed rats, an increase in iNOS
      activity and a decrease in cNOS activity in the gastric mucosa are closely
      related to the development of gastric mucosal lesions.

PMID- 9240425
TI  - Lack of induction of tissue transglutaminase but activation of the preexisting
      enzyme in c-Myc-induced apoptosis of CHO cells.
AB  - The intracellular activity and expression of tissue transglutaminase, which
      crosslinks proteins through epsilon(gamma-glutamyl)lysine isodipeptide bond, was
      investigated in CHO cells and those stably transfected with either inducible c
      Myc (which leads to apoptosis) or with c-myc and the apoptosis inhibitor Bcl-2.
      Protein-bound cross-link content was significantly higher when apoptosis was
      induced by c-Myc while the concomitant presence of Bcl-2 markedly reduced both
      apoptosis and enzymatic protein cross-linking. The expression of tissue
      transglutaminase did not change following the initiation of apoptosis by c-Myc or
      when it was blocked by Bcl-2. Studying transiently co-transfected elements of the
      mouse tissue transglutaminase promoter linked to a reporter enzyme revealed their
      overall repression in cells expressing c-Myc. This repression was partially
      suspended in cells also carrying Bcl-2. Our data suggest that tissue
      transglutaminase is not induced when c-Myc initiates apoptosis but the pre
      existing endogenous enzyme is activated.

PMID- 9240426
TI  - Regulation of early endosome fusion by phospholipase D activity.
AB  - In vitro or cell-free assays of homotypic fusion between early endosomes have
      provided several insights into the means by which an intracellular membrane
      fusion event can be regulated. In this report we show that homotypic fusion
      between early endosomes from baby-hamster kidney cells is partially blocked by
      340 mM ethanol (2% v/v) and by 100 mM butan-1-ol, but not by the secondary
      alcohol butan-2-ol. We ascribe the effect of primary alcohols to their
      participation in a well-characterised transphosphatidylation reaction catalysed
      by phospholipase D activity, which results in the production of
      phasphatidylalcohol at the expense of phosphatidic acid. In accordance with this
      interpretation, we find that addition of exogenous phospholipase D results in
      stimulation of early endosome fusion.

PMID- 9240427
TI  - Cigarette smoke extract inhibits plasma paraoxonase activity by modification of
      the enzyme's free thiols.
AB  - Cigarette smoking is associated with an increased incidence of premature
      atherosclerosis. Minimal information is available at the molecular level
      concerning the mechanism of action of cigarette smoke. Recent work has shown that
      paraoxonase (PON) protects low density lipoprotein against oxidation by Cu2+. The
      goal of the present study was to investigate the effect of cigarette smoke
      extract (CSE) on human plasma paraoxonase activity. The activity of paraoxonase
      was inhibited by the CSE in a dose- and time-dependent manner. The inhibition of
      PON activity by the CSE was reversed by the addition of glutathione or N-acetyl
      cysteine. Furthermore, we tested to see whether sulfhydryl compounds prevented
      the inhibition of PON activity caused by CSE. Sulfhydryl compounds prevented the
      inhibition of PON activity caused by CSE. But any amino compounds, such as N
      acetyl lysine, N-acetyl arginine and aminoguanidine, failed to protect PON
      activity, indicating a specificity with regard to the ability of free thiols to
      buffer the deleterious components of CSE which inhibited PON activity. The
      observed inhibition of PON activity by CSE may account for the increased
      incidence of cardiovascular disease known to be present in smokers through the
      oxidative process of low density lipoprotein and its subsequent uptake by
      macrophage.

PMID- 9240428
TI  - Molecular characterization of the novel basic helix-loop-helix protein DEC1
      expressed in differentiated human embryo chondrocytes.
AB  - The differentiation of human embryo chondrocytes was markedly induced by the
      addition of Bt2cAMP to the culture medium. Using this culture system, a novel
      human cDNA for a basic helix-loop-helix (bHLH) protein (named DEC1) expressed
      primarily in the chondrocytes in response to Bt2cAMP was cloned by the
      subtractive hybridization method. DEC1 protein consists of 412 amino acids and
      exhibits structural similarities to the mammalian HES family, Drosophila hairy,
      and Enhancer of split m7 in the bHLH region. Northern blot analysis showed that
      DEC1 mRNA was expressed in various tissues including the cartilage, lung, spleen,
      and intestine, but not in the brain. These findings suggest that the bHLH factor
      DEC is involved in the control of cell differentiation in several tissues
      including cartilage.

PMID- 9240429
TI  - Eotaxin expression and eosinophilic inflammation in asthma.
AB  - Asthma is a chronic inflammatory disease of the airways characterized by a marked
      infiltration of eosinophils in the bronchial mucosa, and the mechanisms that
      cause the selective recruitment of these cells are areas of active investigation.
      In this study, we found increased expression of the eosinophil chemoattractant
      eotaxin in bronchial mucosa of asthmatic patients. The increase in number of
      cells expressing eotaxin mRNA correlated with the number of eosinophils in the
      bronchial tissue and with two major clinical and functional indices of disease
      severity, suggesting that eotaxin is involved in the recruitment of eosinophils
      and in eosinophil-induced tissue damage in asthma. Cell sources of eotaxin were
      bronchial epithelial cells, T lymphocytes, macrophages and eosinophils
      themselves. The use of drugs that interfere with eotaxin synthesis and function
      may represent a more specific approach in asthma treatment.

PMID- 9240430
TI  - CYP4T1--a cytochrome P450 expressed in rainbow trout (Oncorhynchus mykiss) liver.
AB  - Total RNA isolated from a rainbow trout (Oncorhynchus mykiss) liver was subjected
      to RT/PCR using degenerate primers designed from homologous regions amongst
      cytochrome P450 CYP4 proteins. PCR amplification resulted in a single
      electrophoretic band which was excised, purified and sequenced directly, using
      cycle sequencing. The deduced protein sequence demonstrated the closest amino
      acid identity to rabbit CYP4B1 (54.6%) and rat CYP4B2 (55.4%). Phylogenic
      analysis of this sequence was found to be significantly different to any other
      CYP4 sequence and has been named CYP4T1. This represents the first CYP4 family
      member to be identified in an aquatic vertebrate.

PMID- 9240431
TI  - Isolation of a cytochrome P450 3A cDNA sequence (CYP3A30) from the marine teleost
      Fundulus heteroclitus and phylogenetic analyses of CYP3A genes.
AB  - A reverse transcriptase polymerase chain reaction (RT-PCR) protocol, using
      degenerate PCR-primers specific to highly conserved regions of mammalian CYP3A
      genes, was employed to amplify a 400 base pair cDNA fragment from Fundulus
      heteroclitus liver RNA. The 124 amino acid sequence deduced from this cDNA
      sequence was aligned with corresponding sequences from representative members
      from the CYP1, 2, 3, and 4 gene families retrieved from the GenBank database.
      Phylogenetic trees were constructed using distance-matrix and maximum parsimony
      methods. The F. heteroclitus sequence and all mammalian CYP3A sequences cluster
      together when compared to sequences of members of CYP gene families 1, 2, and 4.
      This fish sequence was 57 to 70% identical to the corresponding region of
      mammalian CYP3A genes. These data indicate that the sequence obtained from F.
      heteroclitus represents a teleost fish CYP3A gene and it has been designated
      CYP3A30.

PMID- 9240433
TI  - Synthesis, uptake, and intracellular metabolism of a hydrophobic tetrapeptide
      peptide nucleic acid (PNA)-biotin molecule.
AB  - Peptide nucleic acid (PNA) molecules are very promising tools for antigene and
      antisense therapies because of their remarkable refractoriness to degradation in
      biological fluids. However, very limited information is available on their uptake
      by potentially target cells and on their intracellular fate. A membrane
      diffusable and fluorescence detectable PNA chimera, Phe-Leu-Phe-Leu-(Adenine)3
      biotin, was obtained by solid phase peptide synthesis and characterized by
      combined HPLC and mass spectrometry (MS). This PNA chimera was found to permeate
      across the membrane of both human erythrocytes and B Namalwa cells much more
      extensively and rapidly than a control Gly-(Adenine)3-biotin PNA molecule.
      Fluorescence patterns of internalization were consistent for a diffusion process
      resulting in the appearance of uniform cytoplasmic distribution of the
      hydrophobic peptide-PNA chimera in the Namalwa cells. Degradation of the
      synthesized PNA chimera by cell lysates and to a much slower extent by the intact
      Namalwa cells was investigated by HPLC-MS analyses of the corresponding methanol
      extracts . It involved the progressive removal of each of the hydrophobic amino
      acid residues, while the linkage with the biotin label was completely resistant
      to cleavage. These results hold promise for the design and synthesis of membrane
      permeable PNA sequences suitable for antigene therapies.

PMID- 9240432
TI  - An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying
      enzyme genes through antioxidant response elements.
AB  - The induction of phase II detoxifying enzymes is an important defense mechanism
      against intake of xenobiotics. While this group of enzymes is believed to be
      under the transcriptional control of antioxidant response elements (AREs), this
      contention is experimentally unconfirmed. Since the ARE resembles the binding
      sequence of erythroid transcription factor NF-E2, we investigated the possibility
      that the phase II enzyme genes might be regulated by transcription factors that
      also bind to the NF-E2 sequence. The expression profiles of a number of
      transcription factors suggest that an Nrf2/small Maf heterodimer is the most
      likely candidate to fulfill this role in vivo. To directly test these questions,
      we disrupted the murine nrf2 gene in vivo. While the expression of phase II
      enzymes (e.g., glutathione S-transferase and NAD(P)H: quinone oxidoreductase) was
      markedly induced by a phenolic antioxidant in vivo in both wild type and
      heterozygous mutant mice, the induction was largely eliminated in the liver and
      intestine of homozygous nrf2-mutant mice. Nrf2 was found to bind to the ARE with
      high affinity only as a heterodimer with a small Maf protein, suggesting that
      Nrf2/small Maf activates gene expression directly through the ARE. These results
      demonstrate that Nrf2 is essential for the transcriptional induction of phase II
      enzymes and the presence of a coordinate transcriptional regulatory mechanism for
      phase II enzyme genes. The nrf2-deficient mice may prove to be a very useful
      model for the in vivo analysis of chemical carcinogenesis and resistance to anti
      cancer drugs.

PMID- 9240434
TI  - Immunohistochemical localization of advanced glycation end products, pentosidine,
      and carboxymethyllysine in lipofuscin pigments of Alzheimer's disease and aged
      neurons.
AB  - Lipofuscins are intracellular fluorescent pigments accumulating in the central
      nervous system (CNS) with aging and degenerative processes such as Alzheimer's
      disease (AD). Although they are thought to be lipid peroxidation products derived
      from malondialdehyde, their biogenesis remains controversial. We further
      characterize the chemical nature of lipofuscins in brain tissues from AD patients
      and normal aged subjects. Advanced glycation end products (AGEs), pentosidine and
      carboxymethyllysine (CML), were identified by appropriate specific antibodies.
      They have physicochemical properties similar to those of lipofuscin and also
      increase with aging. Pentosidine and CML were identified in the neuronal
      perikarya and the extraneuroperikaryal deposits of both the AD and aged brain.
      Pentosidine, but not CML, was present in the fiber-like structure within the
      neuropil and the core of classical senile plaque. In the brain of young subjects
      without CNS disease, pentosidine and CML staining was faint. Pentosidine and CML
      co-localized with lipofuscin pigments in the neuronal perikarya of both the AD
      and aged brain. We demonstrate for the first time that lipofuscin is constituted
      not only of lipid peroxidation products but also from glycation products which
      may be the origin of fluorescent pigments. Lipofuscins should thus be considered
      as fluorescent pigments generated by lipid- and sugar-derived Schiff base-protein
      polymers.

PMID- 9240435
TI  - Characterization of the pleckstrin homology domain of Btk as an inositol
      polyphosphate and phosphoinositide binding domain.
AB  - We previously reported that the pleckstrin homology (PH) domain of Bruton's
      tyrosine kinase (Btk) binds Ins(1,3,4,5)P4 and that missense mutations in this
      domain which cause either human X-linked agammaglobulinemia (XLA) or murine X
      linked immunodeficiency (Xid) also dramatically reduce the Ins(1,3,4,5)P4 binding
      activity. In this paper, we describe the inositol phosphate binding specificity
      of the Btk PH domain and different inositol polyphosphate binding properties
      among the PH domains of Tec family kinases. Our results suggest that certain
      inositol phosphates and/or phosphoinositides are physiological ligands of some
      Tec family kinases and that Tec family members are differently regulated by
      inositol molecules.

PMID- 9240437
TI  - A colorimetric inhibition study of single-stranded DNA decamer sequence
      interactions with dinitrotoluene.
AB  - A novel colored reaction between 2,4-dinitrotoluene (DNT) and dimethylsulfoxide
      (DMSO) on carbonate-activated plastic surfaces is described. In a preliminary
      study of the potential of oligonucleotides to bind nitroaromatic explosives, a
      random library of 1,040 single stranded (ss) DNA decamers (10 bases) in
      polystyrene microtitre plates were screened for inhibition of color development.
      The vast majority (89%) of sequences in the library completely inhibited color
      formation, suggesting that hydrogen bonding between DNA and the nitro groups of
      DNT was the predominate attractive force. Of the 114 sequences which allowed some
      visible color development, absorbance (405 nm) values were negatively correlated
      with GC content (r = -0.764), suggesting that some specific binding "pocket"
      structures for DNT may exist in the small library examined. Among the color
      evolving combinations, differences in amount of DNA were not correlated with
      absorbance.

PMID- 9240436
TI  - Apamin-sensitive Ca2+-dependent K+ current and hyperpolarization in human
      endothelial cells.
AB  - Vascular endothelial cells have several types of Ca2+-dependent K+ current (I(K
      Ca)). Here, we describe apamin-sensitive I(K-Ca) which is activated by treatment
      with histamine (His) in human umbilical vein endothelial cells (HUVECs). In 65 %
      of HUVECs examined, 100 nM apamin potently inhibited I(K-Ca) and
      hyperpolarization induced by His (19 and 7 % of control, respectively). In
      contrast, application of 5 mM tetraethylammonium, a non-selective K channel
      blocker, or 100 nM iberiotoxin, a selective K channel blocker for a large
      conductance Ca2+-dependent K+ channel, had small (78 % of control) or no effects
      (102 % of control) on I(K-Ca), respectively. These findings suggest that apamin
      sensitive Ca2+-dependent K+ channels are expressed in HUVECs and activated by
      receptor stimulation.

PMID- 9240438
TI  - Long-term, stable expression of green fluorescent protein in mammalian cells.
AB  - Despite the proven utility of green fluorescent protein (GFP) as a reporter
      molecule for transient gene expression, the adequacy of this marker for models
      requiring durable, high-level gene expression has not been fully tested. To
      address this issue, we performed the transfection of Chinese Hamster Ovary (CHO)
      cells with plasmid DNA encoding both GFP and neomycin phosphotransferase (neo)
      cassettes. The expression of GFP was measured after the cells were cultured in
      the presence or absence of G418-mediated selective pressure. After removal of
      G418 from the growth medium, the percentage of pooled G418 resistant
      transfectants which co-expressed the GFP transgene increased or remained
      unchanged. Flow cytometric and visual isolation of GFP-expressing cells was
      possible without continued selection in G418. One cloned cell line, C463,
      maintained high-level green fluorescence for 18 weeks in G418 and an additional
      12 weeks in nonselective medium. Our data suggest expression of GFP does not
      confer a growth disadvantage in mammalian cells.

PMID- 9240439
TI  - Quantification of the cAMP response element binding protein in ventricular
      nuclear protein from failing and nonfailing human hearts.
AB  - Alterations in the expression of myocardial regulatory proteins (e.g. beta
      adrenoceptor, inhibitory G-proteins) in human heart failure are associated with
      excessive stimulation of the cAMP signalling pathway by endogenous
      catecholamines. The transcription factor cAMP response element binding protein
      (CREB) mediates cAMP-dependent transcriptional activation and is expressed in the
      human heart. Here, CREB protein was immunologically quantified in ventricular
      nuclear protein preparations from nonfailing donor hearts (n = 8) and from
      failing hearts transplanted due to dilative (n = 10) or ischemic cardiomyopathy
      (n = 6). CREB expression was unchanged in ventricular nuclei from failing hearts
      compared to the nonfailing controls suggesting that expressional alterations in
      human heart failure cannot be explained by altered expression of CREB.

PMID- 9240440
TI  - Effects of metal ions on the binding activity of the human leukocyte leukotriene
      B4 receptor.
AB  - The specific binding of leukotriene B4 to its receptor on human leukocyte
      membranes was enhanced in a dose-dependent manner by metal ions. Mg2+ and Ca2+
      were the most potent followed by Mn2+ and Co2+. These divalent cations increased
      receptor density and did not affect the binding affinity. Addition of the same
      divalent cations to a partially purified receptor prepared by precipitation with
      polyethylene glycol produced a greater effect, whereby both binding affinity and
      receptor density were significantly increased. Zn2+ inhibited activity in both
      preparations by decreasing the density of receptors. In the membrane preparation,
      binding activity was decreased by Na+ and increased by K+, while Li+ had no
      effect. However, in the partially purified receptor preparation, these monovalent
      cations all increased the binding activity. Our findings show that purification
      of the leukotriene B4 receptor modifies its response to various monovalent and
      divalent cations, perhaps by removing certain cellular components involved in
      receptor regulation.

PMID- 9240441
TI  - The amino terminal deletion mutants of hepatitis C virus nonstructural protein
      NS5A function as transcriptional activators in yeast.
AB  - To investigate the biological function of hepatitis C virus (HCV)-NS5A, the NS5A
      was fused at its N-terminus with the DNA binding domain (DBD) of yeast
      transcriptional activator GAL4 (GAL4-DBD). The GAL4-DBD alone had no
      transcriptional activation function. However, a mutant of the GAL4-DBD/NS5A
      fusion protein, in which 129 amino acid residues were deleted from the N-terminus
      of NS5A, exhibited strong transcriptional activation in yeast cells, bearing the
      Escherichia coli lacZ reporter gene encoding the beta-galactosidase under the
      transcriptional control of GAL4 promoter and TATA box. Further mutational
      analysis of NS5A revealed that the region between the amino acid residues 130 to
      352 were critical for optimal level of transactivation. This region includes two
      acidic domains and one proline-rich region which have been shown to be involved
      in the function of several transcriptional activators.

PMID- 9240442
TI  - Nitric oxide inhibits CPP32-like activity under redox regulation.
AB  - The inhibitory effect of nitric oxide (NO) on the enzymatic activity of CPP32
      like proteases in the cell extract from vincristine-treated cells was examined in
      vitro. NO generated from (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy
      S-hexen eamide (NOR1) inhibited CPP32-like protease, which constitute a family of
      interleukin-1beta-converting enzyme (ICE)-like proteases in a dose-dependent
      manner. Moreover, recombinant CPP32beta activity was inhibited by NOR1 at same
      concentration. Inhibition of CPP32-like activity by NO was reversed in the
      presence of glutathione in the enzymatic reaction mixture. Thus, CPP32-like
      activity was regulated by NO under redox regulation. These findings suggest that
      NO may prevent apoptosis by inhibiting the ICE protease cascade under the
      influence of cellular redox status.

PMID- 9240443
TI  - Detection and characterization of alpha-crystallin intermediate with maximal
      chaperone-like activity.
AB  - Lens alpha-crystallin has been reported to act like a chaperone molecule, with
      the chaperone-like activity enhanced by partial unfolding. The nature of the
      partial unfolding, however, is not fully understood. In this project, the
      unfolding and refolding process of alpha-crystallin was studied with guanidine
      hydrochloride (GdnHCl). Trp fluorescence (tertiary structure) and far-ultraviolet
      circular dichroism (UVCD) (secondary structure) demonstrated the presence of an
      intermediate in the unfolding pathway. ANS (1-anilino-8-naphthalenesulfonate)
      fluorescence clearly indicated a two-step transition in the unfolding-refolding
      process and showed that maximum hydrophobicity of the alpha-crystallin occurred
      at 0.8-1.0 M GdnHCl. This alpha-crystallin intermediate appears to be in a molten
      globule state; conformational study by near- and far-UVCD measurements indicated
      that alpha-crystallin intermediate exhibited tertiary structure which was
      significantly altered from that of the native protein, but had nearly the same
      secondary structure. Quaternary structure (size of aggregate) of the intermediate
      also remained unchanged from that of the native protein, as shown by FPLC size
      exclusion chromatography. The maximal hydrophobicity of the alpha-crystallin
      intermediate in the unfolding-refolding pathway was accompanied by maximal
      protection of betaH-crystallin from aggregation. However, an adverse effect of
      partial unfolding is that the alpha-crystallin intermediate aggregates at high
      concentrations. Together, these results clearly demonstrated the biological
      significance of the alpha-crystallin intermediate: it is a more effective
      chaperone than native alpha-crystallin.

PMID- 9240444
TI  - Effects of apo E deficiency on plasma lipid levels in mice lacking APOBEC-1.
AB  - Apolipoprotein (apo) B100 mRNA undergoes site specific C to U editing, generating
      a stop-translation codon of apo B48 in the small intestine. This reaction is
      catalyzed in an editosome which contains APOBEC-1, a catalytic subunit. To
      clarify the functional significance of the apo B mRNA editing in lipoprotein
      metabolism, we have generated APOBEC-1 knockout mice and double knockout mice
      which are deficient in both APOBEC-1 and apo E. The apo B mRNA editing activity
      was markedly reduced and complete elimination of apo B48 from the plasma was
      observed in APOBEC-1(-/-) mice. Plasma triglyceride levels significantly
      increased in the double knockout mice (APOBEC-1(-/-);apo E(-/-)) as compared to
      apo E(-/-) mice. These results suggest that APOBEC-1(-/-) mice are a valuable
      model for experiments designed to understand a role of apo B mRNA editing.

PMID- 9240445
TI  - Role of metabolic intermediates in lipopolysaccharide/cytokine-mediated
      production of nitric oxide in isolated mouse hepatocytes.
AB  - Induction of nitric oxide synthase by bacterial endotoxin in vivo can be mimicked
      by treating cultured hepatocytes with a combination of lipopolysaccharide and
      cytokines (LPS/cytokines), but the role of LPS/cytokine-induced nitric oxide in
      hepatocyte glucose metabolism is ambiguous. In this study, intermediary
      metabolite effects on LPS/cytokine-induced hepatocyte nitric oxide synthesis were
      examined. Pyruvate, lactate, oxaloacetate, and fumarate all showed some
      inhibitory effects on hepatocyte nitric oxide synthesis. However, these metabolic
      intermediates could not improve the mitochondrial respiration of LPS/cytokine
      treated hepatocytes. Phosphoenolpyruvate carboxykinase activity (or flux)
      relating factors, glucocorticoids and cAMP, also blocked LPS/cytokine-induced
      nitric oxide synthesis. Insulin was much less potent than cAMP and
      glucocorticoids, and phorbol ester did not show any effect on hepatocyte nitric
      oxide synthesis. These results suggest that LPS/cytokine-induced nitric oxide
      synthesis is related, at least partly, to phosphoenolpyruvate carboxykinase
      activity (or flux) in hepatocytes.

PMID- 9240446
TI  - Cloning, sequencing, and characterization of the ftsZ gene from coryneform
      bacteria.
AB  - Taking advantage of highly conserved domains present in the ftsZ genes from
      Escherichia coli, Rhizobium meliloti, and Bacillus subtilis, we designed
      degenerate oligonucleotides (oligos) corresponding to these regions. These oligos
      were used as primers in PCR in order to amplify DNA sequences from Brevibacterium
      flavum MJ233 chromosomal DNA. The PCR product was used as a probe to recover
      genomic fragments from a lambda library of Br. flavum MJ233. The complete
      nucleotide sequence (nt) of the cloned 4.2-kb EcoRI fragment containing the ftsZ
      homolog from Br. flavum MJ233 indicated that the deduced gene product of the Br.
      flavum ftsZ homolog is composed of 438 amino acids (aa) with a deduced molecular
      weight of 46.9 kDa. This size of molecular weight was also confirmed by the in
      vitro protein synthesis assay. Comparison of this aa sequence to the
      corresponding sequences from E. coli, Rh. meliloti, B. subtilis, and Streptomyces
      coelicolor revealed a high degree of conservation and suggested that the Br.
      flavum ftsZ homolog has a putative GTP binding motif and a GTP hydrolizing
      region. Expression of Br. flavum ftsZ gene in E. coli, JM109 inhibited its cell
      division, leading to filamentation. This suggested that the Br. flavum ftsZ
      product competed with the E. coli ftsZ product.

PMID- 9240447
TI  - Cloning, mapping, and tissue distribution of a human homologue of the mouse jerky
      gene product.
AB  - Inactivation of the jerky gene by insertion of a transgene into the mouse genome
      results in epileptic seizures in transgenic mice. This finding indicates that the
      jerky gene plays an important role in inducing epilepsy syndromes in mice. We
      report here our efforts in cloning, chromosomal mapping, and analysis of tissue
      distribution of a novel human gene, the HHMJG, a homologue to the mouse jerky
      gene product. We have successfully identified a full length cDNA clone encoding a
      novel human protein homologous to the mouse jerky gene product. The finding was
      based on the result of an analysis of EST (expressed sequence tag) sequences of a
      clone from a human tonsil cDNA library. A 4.0 kb mRNA species of the HHMJG is
      abundantly expressed in the majority of human tissues examined, including brain
      and skeletal muscle. However, in the testes, two mRNA species of the HHMJG,
      approximately 2.0 and 4.0 kb, are abundantly expressed. Sequence analysis of the
      HHMJG cDNA indicates that it encodes a putative protein of 51 kD, which shares
      significant sequence homology to not only the mouse jerky gene product but also
      some nuclear regulatory proteins, such as centromere binding protein-B. The
      predicted nuclear localization of the HHMJG product suggests that this protein
      may function as a nuclear regulatory protein. The result of human chromosomal
      mapping shows that the HHMJG is located on human chromosome 11q21. Our
      identification of the HHMJG cDNA provides a potential gene candidate to further
      investigate the biological significance and clinical implications of the HHMJG in
      human epilepsy.

PMID- 9240448
TI  - Growth inhibition and induction of apoptosis by HGF in transformed rat liver
      epithelial cells.
AB  - Recently we demonstrated in a transgenic mouse model that hepatocyte growth
      factor (HGF) inhibits c-myc dependent hepatocarcinogenesis. The inhibitory
      effects of HGF in carcinogenesis were further characterized using a series of rat
      liver epithelial (RLE) cell lines which were transformed in vitro with either
      aflatoxin or oncogenes, or spontaneously. HGF caused a cytostatic effect and
      enhanced cell motility in spontaneously and aflatoxin-transformed cells. In
      normal RLE cells HGF was slightly stimulatory and did not induce scattering. The
      HGF receptor was tyrosine phosphorylated in all cell lines, indicating that it is
      functionally active and capable of signaling events. In the aflatoxin transformed
      cells HGF also induced apoptosis, associated with constitutive c-myc expression
      and 1 Kb bax-alpha transcripts. These findings indicate that transformed RLE cell
      lines may provide a useful model to further examine the mechanism(s) by which HGF
      and its receptor modulate neoplastic development.

PMID- 9240449
TI  - Biotin synthase, a new member of the family of enzymes which uses S
      adenosylmethionine as a source of deoxyadenosyl radical.
AB  - The fact that biotin synthase, from Escherichia coli and Bacillus sphaericus,
      requires S-adenosylmethionine and a reducing system led us to postulate that this
      synthase could belong to the family of enzymes which use S-adenosylmethionine as
      a source of deoxyadenosyl radical, namely pyruvate formate-lyase, lysine 2,3
      aminomutase, and anaerobic ribonucleotide reductase. We describe here experiments
      with S-[2,8-(3)H] adenosylmethionine and S-adenosyl-[methyl-3H]methionine which
      allowed the identification and quantification of the expected cleavage products,
      deoxyadenosine, and methionine. They are formed in equimolar amounts, in a ratio
      close to 3 with respect to the biotin produced. We postulate a mechanism
      involving the homolytic cleavage of two C-H bonds which should consume two
      equivalents of S-adenosylmethionine. The observed excess of S-adenosylmethionine
      consumption is attributed to abortive processes.

PMID- 9240450
TI  - Degenerative changes in spermatogonia are associated with loss of glucose
      transporter (Glut 3) in abdominal testis of surgically induced unilateral
      cryptorchidism in rats.
AB  - Expression of facilitative glucose transporters (Glut 1, 2 and 3) was examined by
      Western blot analyses 10, 20 and 30 days following surgically induced unilateral
      abdominal cryptorchidism. The cryptorchid testes exhibited marked degenerative
      changes in the seminiferous tubules and spermatogonia, impaired and incomplete
      spermatogenesis and lack of spermatozoa in the lumen. Immunoblotting of testis
      proteins with Glut transporter antibodies revealed only the presence of Glut 2
      and 3 proteins. Glut 2 expression in abdominal testis was increased (45%, 67%,
      and 40% at 10, 20 and 30 days, respectively) but no significant change was
      observed in contralateral scrotal testis. Glut 3 expression was reduced by 85-95%
      compared with contralateral scrotal testis. A significant decrease in Glut 3
      levels in abdominal testis was accompanied by an increase in scrotal testis Glut
      3 content (80%, 144% and 212% at 10, 20 and 30 days, respectively) compared to
      age matched control rats. These results suggested that the degenerative changes
      in abdominal testis may be associated with decreased Glut 3 mediated glucose
      transport in seminiferous tubules and spermatogonia.

PMID- 9240451
TI  - Nonenzymatic lactosylation of bovine beta-lactoglobulin under mild heat treatment
      leads to structural heterogeneity of the glycoforms.
AB  - Lactose reacts nonenzymatically with beta-lactoglobulin (beta-LG), the major whey
      protein, under mild heat treatment and the formation of the complex may be
      monitored by mass spectrometry. Using Reverse Phase HPLC coupled with
      Electrospray Ionization MS (ESI-MS) we have measured the global extent of
      glycosylation and examined the distribution of lactose among the beta-LG
      glycoforms. Identification of lactosylated sites by trypsinolysis and Tandem MS
      indicate that, although the glycosylation reaction was non-specific and
      potentially involved all the reactive sites (alpha- and epsilon-amino groups),
      beta-LG appeared to have at least two populations of lysine with the distinct
      ability to react with lactose. These results underline the structural
      heterogeneity of beta-LG glycoforms, with respect to the number of lactose linked
      per molecule and to the binding sites involved, which could affect the biological
      function of beta-LG.

PMID- 9240452
TI  - DIF-1, putative morphogen of D. discoideum, suppresses cell growth and promotes
      retinoic acid-induced cell differentiation in HL-60.
AB  - Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces
      stalk cell formation in the cellular slime mold Dictyostelium discoideum. In this
      study, we have examined the effects of DIF-1 on the human leukemia HL-60 cells.
      DIF-1 at 10-40 microM suppressed cell growth in a dose-dependent manner, and
      approximately 50% growth inhibition was attained with 15-20 microM DIF-1. FACS
      analysis of cell-cycle phase distribution using propidium iodide revealed that
      many cells were accumulated in the G1 phase after treatment with 15-20 microM DIF
      1. These concentrations of DIF-1 also raised [Ca2+]i in a dose-dependent manner
      irrespective of the presence of extracellular Ca2+, indicating that DIF-1
      elicited Ca2+-release from some intracellular Ca2+ store(s). Most importantly,
      relatively low concentrations of DIF-1 (1-5 microM) were found to promote
      retinoic acid-induced cell differentiation. The present results indicate that DIF
      1 may be a useful tool for the analysis of myeloid cell differentiation and have
      therapeutic potential in the treatment of human myeloid leukemia.

PMID- 9240453
TI  - Anti-Ca2+, Mg2+-dependent endonuclease antibody detects specifically a class of
      chromatin-bound endonuclease.
AB  - A polyclonal antibody against purified bull seminal plasma Ca2+, Mg2+-dependent
      endonuclease was raised in a rabbit. The antibody specifically cross-reacted with
      chromatin-bound Ca2+, Mg2+-dependent endonucleases from bovine thymus, human
      placenta, and bovine, rat and mouse liver in addition to the bovine seminal
      enzyme. The antibody did not cross-react with other endonucleases examined,
      including the acid-endonucleases from bovine thymus and liver, porcine spleen
      DNase II, micrococcal nuclease, and bovine pancreas DNase I, a known Ca2+ and
      Mg2+ requiring endonuclease. The present results indicate that this antibody
      specifically recognizes a class of so-called Ca2+, Mg2+-dependent endonuclease,
      which is localized in cell nuclei of various tissues and is probably involved in
      chromatin degradation during apoptosis. The antibody will be used to study the
      functional role of this class of endonuclease.

PMID- 9240454
TI  - The genomic organization of the genes for human lipopolysaccharide binding
      protein (LBP) and bactericidal permeability increasing protein (BPI) is highly
      conserved.
AB  - We have determined the exon/intron organization of the human lipopolysaccharide
      binding protein (LBP) and bactericidal permeability increasing protein (BPI)
      genes. The LBP gene spans approximately 28.5 kb and is composed of 14 exons while
      the 31.5-kb-long BPI gene is composed of 15 exons. Comparison of the genomic
      organization of the LBP and BPI genes together with the genomic structures of the
      PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer
      protein) genes, which all together constitute a gene family of functionally
      related proteins, revealed high homology with a remarkable conservation of
      exon/intron transitions. The exon/intron junctions of the LBP, BPI, and PLTP
      genes are almost identical, with most of the exons being of the same size. In
      addition, functional domains are conserved in these proteins. The C-terminal
      octapeptide important for CETP anchoring in lipoprotein particles is also present
      in LBP, BPI, and PLTP. The LPS binding motif in exons 3 and 4 has been retained
      in LBP and BPI. Our results indicate that the LBP, BPI, and PLTP genes, and
      probably the CETP gene, may have evolved from a common primordial gene and may
      share similar functional properties.

PMID- 9240455
TI  - Role of CYP1A2 in hepatic sequestration of dioxin: studies using CYP1A2 knock-out
      mice.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin), most potent of the
      polyhalogenated aromatic hydrocarbons, has been studied in a variety of
      genetically normal species. Transgenic mice lacking a cytochrome P450 1A2 gene
      were used to study the influence of the CYP1A2 gene on the hepatic sequestration
      and distribution of TCDD, 4-PeCDF (2,3,4,7,8-pentachlorodibenzofuran; dioxin-like
      compound), and PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl; non-dioxin-like PCB
      (polychlorinated biphenyl)). The knock-out mice were compared to their age
      matched lineage strains of C57BL/6N (1A2+/+; Ah(b)) and 129/Sv (1A2+/+; Ah(d))
      for each compound. As demonstrated by the liver-to-adipose tissue (L/F)
      concentration ratios, there was no hepatic sequestering of TCDD and 4-PeCDF in
      the transgenic knock-out mice.

PMID- 9240456
TI  - The role of cytochrome b5 in 4alpha-methyl-oxidation and C5(6) desaturation of
      plant sterol precursors.
AB  - The electron donors for the membrane-bound sterol-4alpha-methyl-oxidases and
      sterol C5(6)-desaturase of plant sterol biosynthesis have not been previously
      identified. The requirement of cytochrome b5 to shuttle reducing equivalents from
      NAD(P)H to 4,4-dimethylsterol-4alpha-methyl oxidase (4,4-DMSO), 4alpha
      methylsterol-4alpha-methyl oxidase (4alpha-MSO), and delta7-sterol-C5(6)
      desaturase (5-DES) was investigated using a purified preparation of IgG raised
      against plant cytochrome b5. The activities of 4,4-DMSO, 4alpha-MSO, and 5-DES,
      three oxidative reactions not mediated by cytochrome P-450, were strongly and
      completely inhibited by the antibody in a microsomal preparation from maize. In
      addition the IgG also inhibited NADH-dependent cytochrome c reduction in the same
      preparation. These results strongly suggest that membrane-bound cytochrome b5 of
      maize microsomes is an obligatory electron carrier from NAD(P)H to 4,4-DMSO,
      4alpha-MSO, and 5-DES.

PMID- 9240457
TI  - Members of the family of IL-6-type cytokines activate Stat5a in various cell
      types.
AB  - Interleukin-6 (IL-6)-type cytokines activate transcription factors Stat1 and
      Stat3 (signal transducers and activators of transcription). Here we report that
      leukemia inhibitory factor (LIF) and IL-6 activate Stat5a in M1 myeloid leukemia
      cells in addition. In murine embryonal stem (ES) cells stably transfected with an
      expression vector for Stat5a treatment with LIF resulted in tyrosine
      phosphorylation and DNA-binding of this transcription factor. Transfection of an
      expression construct for Stat5a in human hepatoma cells caused a dose-dependent
      increase in LIF-triggered transcriptional activity. Our data demonstrate that
      Stat5a is activated by IL-6-type cytokines and can mediate transcriptional
      activity in addition to Stat1 and Stat3.

PMID- 9240458
TI  - The alpha2L111R,N122D isoform of the Na,K-ATPase expressed in HeLa cells does not
      undergo an adipocyte-like increase in activity in response to insulin.
AB  - In the rat adipocyte, insulin increases potassium uptake by a preferential
      activation of the alpha2 isoform of the Na,K-ATPase. The question under
      consideration here is whether expression of the alpha2 isoform is sufficient to
      replicate its differential activation by insulin. Accordingly, we compared the
      effect of insulin on the activity of the ouabain resistant rat alpha1 and
      alpha2RD (alpha2L111R,N122D) isoforms in HeLa cells. In HeLa cells, in contrast
      to the rat adipocyte, insulin produces an increase of equal magnitude in the rate
      of 86Rb+/K+ uptake by the ouabain resistant rat alpha1 and rat alpha2RD subunits.
      We conclude that the mechanism of insulin activation of the alpha2RD isoform in
      HeLa cells differs from that of the wild type alpha2 isoform in the rat
      adipocyte.

PMID- 9240460
TI  - The 6H1 orphan receptor, claimed to be the p2y5 receptor, does not mediate
      nucleotide-promoted second messenger responses.
AB  - An orphan G protein-coupled receptor, termed 6H1, with approximately 30% sequence
      identity to P2Y receptors has been proposed to be a P2Y receptor (p2y5) based
      solely on a radioligand binding assay with [35S]dATP alphaS [Webb et al. (1997)
      Biochem. Biophys. Res. Commun. 219:105-110]. Previous work in our laboratory has
      shown that [35S]-dATP alphaS is not a general ligand for P2Y receptors, and thus
      inclusion of the p2y5 receptor in the family of P2Y receptors is questionable. To
      define unambiguously whether the p2y5 receptor is a P2Y receptor, we have cloned
      the turkey homologue of the chick p2y5 receptor. Sequence analysis indicated that
      the turkey receptor contains an additional 32 amino acids at its carboxy terminus
      compared to the published chick sequence. HA epitope-tagged turkey p2y5 receptors
      were stably expressed in 1321N1 human astrocytoma cells, and cells shown to
      express the HA-tagged p2y5 receptor by an intact cell-based ELISA were used to
      determine whether changes in second messenger levels occurred in response to a
      series of nucleotides. ATP, ADP, UTP, UDP, dATP alphaS, and A2P4 had no effect on
      either inositol phosphate or cyclic AMP concentrations in cells expressing the
      p2y5 receptor. Robust inositol phosphate and cyclic AMP responses occurred to
      other G protein-coupled receptors expressed in 1321N1 cells, which indicate that
      these cells contain all of the necessary signaling components to generate these
      second messenger responses. These data indicate that the 6H1/p2y5 receptor is not
      a member of the P2Y receptor family of signaling proteins.

PMID- 9240459
TI  - Nucleotide binding to autotaxin: crosslinking of bound substrate followed by lysC
      digestion identifies two labeled peptides.
AB  - Autotaxin (ATX) is a 125 kDa glycoprotein motility factor and exoenzyme which can
      catalyze the hydrolysis of either the alpha-beta or at the beta-gamma
      phosphodiester bond in ATP. Its motility stimulating activity requires an intact
      5'-nucleotide phosphodiesterase (PDE) active site. Photolysis-dependent labeling
      of ATX with alpha-[32P]-8-N3-ATP, lysC digestion, and peptide HPLC resolved two
      radioactive fractions containing single peptides whose amino-terminal sequences
      were determined. Peptide A (T210FPNLYTLATG. . .) was derived from the PDE active
      site and peptide B (Y318GPFGPEMTNP. . .) was not previously known to be involved
      in any of the activities of ATX. The differential effect of NaCl concentration on
      the labeling of these two peptides, as well as on the two reaction types
      catalyzed by ATX, allows a classification of activities which predicts both the
      position of preferential peptide labeling by bound ATP and also the position of
      phosphodiester bond hydrolysis.

PMID- 9240462
TI  - Evidence for the formation of F3-isoprostanes during peroxidation of
      eicosapentaenoic acid.
AB  - 8-Epi PGF2alpha, a potent vasocontrictor, is a specific product of non-enzymatic
      peroxidation of arachidonic acid. It seems likely that similar products could
      arise from other polyunsaturated fatty acids (PUFAs) and might be useful
      biomarkers of their peroxidation in vivo. This was investigated using
      eicosapentaenoic acid (EPA). EPA liposomes (1 mg/ml PBS) were exposed at 37
      degrees C to either 2,2'-azobis-(2-amidinopropane) dichloride (AAPH) or copper
      ions at final concentrations of 1 mM and 10 microM, respectively. Sample
      processing involved solid-phase extraction on a C18-followed by an NH2 cartridge.
      After conversion to pentafluorobenzyl ester/trimethylsilyl derivatives, F3
      isoprostanes were analysed by negative ion-chemical ionisation mass spectrometry
      (GC-MS/NICI) using tetradeuterated PGF2alpha (PGF2-d4) as the internal standard.
      Quantitative analysis was carried out by selected ion monitoring of the
      carboxylated anion [M-180] at m/z 567 and 573 for the PGF3-like compounds and
      PGF2-d4, respectively. EPA oxidised by AAPH or by copper ions gave rise to a
      family of F3-isoprostanes with 8-epi PGF3alpha as a minor product. Formation of
      F3-isoprostanes correlated well with other indices of lipid peroxidation
      (hydroperoxides and thiobarbituric acid reactive substances). The possibility of
      analysing specific lipid peroxidation products from individual fatty acids should
      facilitate nutritional and biomedical studies.

PMID- 9240461
TI  - Sequence and analysis of a dnaJ homologue gene in cyanobacterium Synechococcus
      sp. PCC7942.
AB  - The chromosomal region containing a dnaJ gene homologue (dnaJ7942) was sequenced
      from unicellular cyanobacterium Synechococcus sp. PCC7942. The dnaJ7942 gene as
      well as following two orfs are located in the region immediately downstream of
      dnaK3, and they seem to be cotranscribed. The dnaJ7942 gene product shares, like
      all J homologues, homology for the highly conserved "J-domain" of DnaJ. It does
      not have, however, a glycine and phenylalanine (G/F)-rich region nor cysteine
      (Cys)-rich region unlike the Escherichia coli DnaJ protein. When this gene was
      expressed in E. coli, cells became filamentous in contrast to those expressing
      the E. coli dnaJ gene. Gene disruption experiments indicated that the dnaJ7942
      gene was essential for growth. Analysis of subcellular localization revealed that
      the DnaJ protein is mainly located on the thylakoid membrane in the
      cyanobacterium.

PMID- 9240463
TI  - Human islets of Langerhans express multiple isoforms of calcium/calmodulin
      dependent protein kinase II.
AB  - Previous studies have provided evidence for the presence of calcium/calmodulin
      dependent protein kinase II (CaM kinase II) in rodent islets of Langerhans, and
      beta-cell CaM kinase II activity has been correlated with insulin secretion. In
      this study we provide the first conclusive evidence for the expression of CaM
      kinase II in human islets of Langerhans and show that multiple isoforms are
      expressed. Screening of a human islet cDNA library resulted in the isolation of a
      999bp partial cDNA clone encoding CaM kinase II. The nucleotide sequence of the
      islet clone showed a high degree of homology (94.8%) to the two gamma isoforms of
      CaM kinase II previously isolated from human T lymphocytes (gammaB and gammaC).
      In order to obtain full length sequence for the islet clone, rapid amplification
      of cDNA ends (RACE) was used to amplify the 3' end of the islet clone from human
      islet poly A+ RNA. Two distinct gamma isoforms of CaM kinase II were amplified
      from the islet RNA. They were identified as gammaB and gammaE; the latter is
      distinguished from gammaB by a 114bp insertion within the association domain of
      the cDNA. Using reverse transcriptase polymerase chain reaction (RT-PCR) we also
      detected in human islets of Langerhans the novel beta3 isoform of CaM kinase II
      previously reported to be expressed in neonatal rat islets.

PMID- 9240464
TI  - Signaling mechanisms of pertussis toxin-induced myelomonocytic cell adhesion:
      role of tyrosine phosphorylation.
AB  - Pertussis toxin (PTX) was thought to bind Mac-1 integrin receptor (CD11b/CD18) on
      TGF-beta1/D3-primed U937 cells and induced cellular adhesion to serum-coated
      plate. The present study was to investigate the signal transduction pathway
      utilized by PTX to initiate myeloid cell adhesion in serum. Immunoblotting study
      showed that PTX induced tyrosine phosphorylation of two cytoplasmic proteins of
      150 kDa and 90 kDa in TGF-beta1/D3-primed U937 cells in a time-dependent manner.
      In addition, PTX-induced myelomonocytic cell adhesion was abolished in the
      presence of genistein (100 microM), a specific tyrosine kinase inhibitor. 2LPM19c
      (2 microg/ml), a mouse monoclonal antibody against the CD11b subunit of Mac-1
      integrin, or ethylenediamine tetraacetic acid (EDTA, 5 mM) prevented PTX-mediated
      U937 cell adhesion. On the other hand, nifedipine (1 microM), a calcium channel
      blocker, significantly reduced PTX-induced U937 cell adhesion. Taken together, it
      is suggested that binding of PTX to Mac-1 integrin receptor on primed U937 cells
      triggers protein tyrosine phosphorylation and, to a lesser extent, Ca(+2) influx,
      which eventually lead to monocytic cell adhesion in serum.

PMID- 9240466
TI  - Glutamine235 and arginine272 in human melanocortin 5 receptor determines its low
      affinity to MSH.
AB  - The human melanocortin 5 receptor (hMC5R) in the melanocortin receptor family has
      been identified as the receptor with low affinity towards alpha-MSH. Here we show
      that the glutamine at position 235 and arginine at the position 272 in the hMC5R
      are contributing to the low affinity of this receptor. Glutamine235 and
      arginine272 in hMC5R were mutated to lysine (Q235K) and cysteine (R272C),
      respectively, residues which are conserved at these positions in other
      melanocortin receptor subtypes. Upon these mutations affinity of alpha-MSH for
      hMC5R was increased 10-fold for Q235K and 690-fold for R272C mutants,
      respectively. The results explain the unusually low affinity of the hMC5R to the
      melanocortic ligands and suggest the importance of these conserved residues in
      maintaining the high affinity form of melanocortin receptors.

PMID- 9240465
TI  - Overexpression of a 40-kDa protein in human multidrug resistant cells.
AB  - The use of anticancer drugs in the chemotherapeutic treatment of cancer patients
      frequently results in the emergence of drug resistant tumors. Selection of tumor
      cell lines in vitro has led to the identification of several proteins that
      mediate drug resistance to anticancer drugs. In this study, an immuno-dot blot
      method was used to isolate a monoclonal antibody (IPM96) which recognized a 40
      kDa protein (or P-40) co-expressed with P-glycoprotein and MRP in several
      multidrug resistant cell lines (MCF-7/Adr, SKOV/VLB1.0, H69/Adr, and HL60/AR).
      Furthermore, P-40 levels dropped significantly in one revertant cell line
      (H69/PR) derived from H69/AR cells. Interestingly, the expression of P-40 was
      also higher in two tumor cell lines (SKTax6a and A2780CP) that were selected with
      paclitaxel or cisplatin but do not express P-gp or MRP. Immuno-fluorescence
      staining of cells with IPM96 showed both membrane and cytoplasmic staining. These
      results were confirmed by Western blot analysis of different subcellular
      fractions from MCF-7/Adr cells. The membrane bound P-40 was resistant to
      extraction with high salt, chelating agents, and denaturing agents, but was
      solubilized with 10 mM CHAPS. Taken together, the overexpression of P-40 in
      multidrug resistant cells has not been previously determined and therefore could
      be important in the expression of the drug resistance phenotype.

PMID- 9240467
TI  - Antibody-based therapy targeting tumor vascular endothelial cells suppresses
      solid tumor growth in rats.
AB  - We have developed a new approach to antibody-based therapy of solid tumors by
      targeting tumor vascular endothelial cells (EC) which are essential for the
      growth of solid tumors. We investigated the effect of an antibody against tumor
      derived endothelial cells (TEC) on the growth of solid tumors in rats.
      Intravenous administration of TES-23, a monoclonal antibody generated by TEC
      isolated from rat KMT-17 solid tumors, at 1 mg/rat/day for 5 days resulted in
      significant suppression of KMT-17 tumor growth. Histopathological analysis of
      tumors administered with TES-23 showed that adhesion of lymphocytes to EC
      followed by denudation of EC in the viable tumor area. In contrast, little
      obvious toxicity was observed in most of the rat organs examined. These findings
      suggest that the concept of an antibody-based therapy with targeting tumor
      vascular EC would be promising in treatment of solid tumors.

PMID- 9240468
TI  - Monoclonal antibodies against pupa-specific surface antigens of Sarcophaga
      peregrina (flesh fly) hemocytes.
AB  - Monoclonal antibodies were raised against pupal hemocytes of Sarcophaga
      peregrina. Four of the antibodies tested bound specifically to the surface of
      live pupal hemocytes, and these hemocytes appeared to be granulocytes from their
      morphology. The antigen recognized by one of the antibodies, MAb 9C8, was
      considered to be a membrane protein with a molecular mass of 120-kDa. Another
      antibody, MAb 9F3, was found to recognize possibly the same 120-kDa protein and
      two cytoplasmic proteins commonly present in both pupal and larval hemocytes.

PMID- 9240469
TI  - Frzb-1, an antagonist of Wnt-1 and Wnt-8, does not block signaling by Wnts -3A, 
      5A, or -11.
AB  - Frzb-1 is a secreted factor that was recently shown to inhibit signaling by Wnts
      1 and 8. Frzb-1 contains an amino terminal domain that is homologous to the
      Drosophila polarity gene frizzled; several other secreted proteins that share
      this feature have now been identified. These findings raise the question of
      whether or not Frzb-1 is a general inhibitor of signaling by all Wnts. We show
      that signaling of Wnts -3A, 5A, and 11 is not blocked by Frzb-1, demonstrating
      that Frzb-1 can discriminate both between the principle functional Wnt classes
      that have been proposed and within them.

PMID- 9240470
TI  - Cellular response to the redox active lipid peroxidation products: induction of
      glutathione S-transferase P by 4-hydroxy-2-nonenal.
AB  - Membrane lipid peroxidation is known to produce various aldehydic compounds which
      cause a wide range of biological effects including heart disease, aging, and
      cancer. To investigate the effect of lipid peroxidation products on the
      expression of glutathione S-transferases (GSTs), which catalyze the conjugation
      of reactive chemicals with glutathione and play an important role in protecting
      cells, normal rat liver epithelial cells (RL34) were exposed to a variety of
      aldehydic compounds. We found that the GST activity in RL34 cells was induced by
      alpha,beta-unsaturated aldehydes, such as acrolein (1.3-fold), crotonaldehyde
      (1.3-fold), 4-hydroxy-2-hexenal (HHE) (1.4-fold), and 4-hydroxy-2-nonenal (HNE)
      (1.7-fold). The induction of GST activity by HNE was time-dependent, reaching a
      plateau after 16 h. The immunoblot analysis using the polyclonal antibodies
      against GST isozymes demonstrated that GST-P (pi-class), a well-known tumor
      marker, was significantly induced 16 h after the HNE treatment. Also,
      immunostaining for the presence of GST-P confirmed the enhanced expression of GST
      P in the cytoplasm of the cells. Northern blot analysis revealed that the HNE
      treatment of RL34 cells for 1 h enhanced the expression of GST-P mRNA, which
      returned to the control level after 16 h. These data suggest that the induction
      of GST-P by HNE may represent an important cellular defense mechanism against
      oxidative injury.

PMID- 9240471
TI  - The eukaryotic translation initiation factor 5, eIF-5, a protein from Zea mays,
      containing a zinc-finger structure, binds nucleic acids in a zinc-dependent
      manner.
AB  - A maize cDNA encoding the eukaryotic translation initiation factor 5 (eIF-5) has
      been isolated from an 8-day-old seedling cDNA library. The 1975 bp cDNA encodes a
      protein of 451 amino acids, with a predicted molecular weight of 49.04 kDa, and
      hybridizes to a single sequence in the maize genome. The deduced sequence
      contains motifs characteristic of proteins belonging to the GPTase superfamily, a
      zinc finger well conserved in all the protein sequences for eIF-5 reported so
      far, and a fragment also present in prokaryotic and chloroplast L11 ribosomal
      protein. Polymer-binding assays have been used to assess the predicted RNA
      binding property of the protein and to characterize its function. It is shown
      that the eIF-5-encoded protein binds to single-stranded DNA and to polyuridylic
      acid and that the binding is dependent on the presence of Zn2+ ions. These
      results suggest that the zinc-finger structure is involved in the binding of the
      eIF-5 protein to RNA.

PMID- 9240472
TI  - Inhibition of Fas-induced apoptotic cell death by osmotic cell shrinkage.
AB  - Apoptosis is an active physiological mechanism permitting the elimination of
      cells by triggering an intracellular signalling cascade. Here, we tested whether
      osmotic alterations of cell volume interfere with apoptotic cell death in Jurkat
      T-lymphocytes. Apoptotic cell death of Jurkat cells was elicited by activation of
      the Fas receptor which results in sphingomyelinase stimulation, release of
      ceramide, activation of Ras, Rac-proteins and formation of O2. Osmotic cell
      shrinkage inhibited apoptotic cell death induced by the Fas receptor in Jurkat T
      lymphocytes. Osmotic cell shrinkage did not interfere with Fas induced activation
      of the acidic sphingomyelinase or activation of Ras but impaired the formation of
      O2 suggesting an important function of cell volume in the synthesis of reactive
      oxygen intermediates upon Fas receptor ligation.

PMID- 9240473
TI  - The allergen Der p1 induces NF-kappaB activation through interference with
      IkappaB alpha function in asthmatic bronchial epithelial cells.
AB  - Asthma is an inflammatory disease of the airways due to an interaction between
      genetic and environmental factors, and allergy represents the most important
      predisposing trait. Here, we investigated why and how the allergen most often
      implicated in the pathogenesis of asthma and other allergic diseases causes the
      expression of the genes for proinflammatory cytokines in airway epithelium. We
      found that Der p1 promotes activation of transcriptional factor NF-kappaB by
      interference with the function of its cytoplasmic inhibitor IkappaB alpha. This
      is the first report on the effect of an allergen on transcriptional factors. Our
      results improve the understanding of the mechanisms involved in allergic diseases
      and suggest potential therapeutic utility of NF-kappaB blockers.

PMID- 9240474
TI  - Cloning of a cDNA encoding a constitutively expressed rat liver cytosolic
      aldehyde dehydrogenase.
AB  - The presence of a constitutively expressed aldehyde dehydrogenase (ALDH) in the
      rat liver cytosol is controversial (Tottmar et al., 1973; Lindahl and Evces,
      1984; Berger and Weiner, 1977; Tank et al., 1981; Truesdale-Mahoney et al., 1981;
      Cao et al., 1989). A cDNA encoding a constitutively expressed rat liver cytosolic
      class 1 ALDH was cloned using a PCR-based strategy. The open reading frame
      consisted of 1503 nucleotides which encoded a protein of 501 amino acids. In
      order to compare the rat and human nucleotide sequences, we sequenced the entire
      open reading frame of a human liver cytosolic ALDH cDNA clone (Zheng et al.,
      1993). Rat liver constitutively expressed cytosolic ALDH was 99.7, 91.8, 89.0,
      and 83.8% identical to rat kidney, mouse liver, rat liver phenobarbital
      inducible, and human liver cytosolic class 1 ALDH cDNAs, respectively. Northern
      blot analysis indicated that constitutively expressed rat cytosolic ALDH mRNA is
      expressed in lung, kidney, liver, skeletal muscle, and testis, with weak
      expression in heart and brain. These results strongly suggest that a
      constitutively expressed ALDH is present in rat liver cytosol.

PMID- 9240475
TI  - Helicobacter pylori lipopolysaccharide inhibits acid secretion in pylorus-ligated
      conscious rats.
AB  - To examine the effect of Helicobacter pylori lipopolysaccharide on gastric
      secretion, the present study was carried out using pylorus ligated conscious
      rats. Intraperitoneal administration of Helicobacter pylori lipopolysaccharide
      significantly inhibited gastric acid secretion (4 hr) in a dose-dependent manner
      (0.033-1.0 mg/rat). The Helicobacter pylori lipopolysaccharide (1 mg/rat)-induced
      acid inhibition was still observed 8 hr after injection. Gastric acid secretion
      (4 hr) was compared in the rats that had received intraperitoneal administration
      of 1 mg/rat dose of Helicobacter pylori lipopolysaccharide or saline alone 24 hr
      before. There was no significant difference in gastric acid secretion between the
      saline- and H. pylori lipopolysaccharide-treated rats. These results suggest for
      the first time that H. pylori lipopolysaccharide may inhibit acid production, and
      this acid inhibition may be long-lasting. It is also demonstrated that this anti
      secretory action of H. pylori lipopolysaccharide has a reversible effect on
      gastric secretion. All these results suggest that H. pylori lipopolysaccharide
      might be involved in the low acid secretory function seen in patients with acute
      H. pylori infection.

PMID- 9240476
TI  - Identification of side of seizure onset in temporal lobe epilepsy using memory
      tests in the context of reading deficits.
AB  - Sixty patients with temporal lobe epilepsy were classified into reading deficient
      (RD; n = 21) and non-reading deficient (non-RD; n = 39) groups. Selective
      deficits in verbal or nonverbal memory, consistent with side of seizure onset,
      were evident in the non-RD patients. Both verbal and nonverbal memory performance
      were reduced equivalently in individuals with RD, regardless of side of seizure
      onset. As a result, memory tests that were accurate in identifying side of
      seizure onset in the non-RD group were not as accurate in the RD group. When
      individual cases were classified using a clinically applicable decision rule,
      significantly more RD patients were either unclassifiable or incorrectly
      classified than were non-RD patients. Findings suggest that preoperative memory
      data obtained from individuals with epilepsy and evidence of RD may not be as
      valid an indicator of side of seizure onset as are those obtained from patients
      without RD.

PMID- 9240477
TI  - Mental calculation in an autistic savant: a case study.
AB  - We present a detailed investigation of mental calculation in RH, an autistic
      savant. In Experiment 1 RH performed faster and more accurately than control
      subjects in mentally solving multi-digit multiplication problems. However, we
      found no evidence that RH employed short-cut strategies to solve these problems.
      His response times were consistent with application of a left-to-right
      computational procedure employed by expert calculators. He also responded
      extremely quickly to 2-digit squares, suggesting that he may have memorized the
      answers. In Experiment 2 we taught RH a new computational algorithm for
      converting temperatures from Celsius to Fahrenheit. RH was able to learn the new
      algorithm, but required much assistance and made only slight gains with practice.
      RH did not recognize an easy solution strategy based on inverting steps in the
      conversion algorithm. We suggest that the inflexible nature of RH's performance
      may reflect his autistic tendencies coupled with limited intelligence.

PMID- 9240478
TI  - Webster's scattergram method: usefulness for assessing the asymmetry of
      interference between concurrent tasks.
AB  - Webster (1988) described a means of using scattergrams to represent the manual
      and nonmanual data from dual-task laterality experiments in a composite analysis.
      We used Webster's method and the conventional approach (i.e., separate analyses)
      to analyze the results of an experiment in which 40 right-handed adults performed
      a verbal and a manual task concurrently. Whereas separate analyses yielded
      dissimilar outcomes for the two tasks, the scattergram analysis showed that
      overall interference was greater when the right hand performed the manual task
      than when the left hand performed the manual task. Advantages of the scattergram
      method for analyzing dual-task data are discussed.

PMID- 9240479
TI  - Perseverations during paired-associate learning in Huntington's disease.
AB  - Verbal (word) and nonverbal (design) paired-associate tasks were administered to
      Huntington's disease (HD) patients and healthy control subjects. An AB-AC
      paradigm, in which the cue stimuli were paired with different responses on the
      learning (e.g., BED-REST) and test trials (e.g., BED-SHEET), was used. It was
      hypothesized that HD patients would continue to respond with AB associations on
      the AC trials. The results were contrary to expectations: Patients showed
      impaired learning of both verbal and nonverbal associations but did not display a
      perseverative response style, even when the associative strength between word
      pairs was manipulated to elicit perseverations. Patients made more
      nonperseverative than perseverative errors in all conditions, an error pattern
      similar to that of control subjects. HD patients did not demonstrate increased
      susceptibility to proactive interference on these associative learning tasks.

PMID- 9240482
TI  - California Verbal Learning Test: normative data for the elderly.
AB  - Overlapping age tables were developed, separately for males and females, to
      provide additional normative information for the California Verbal Learning Test
      (CVLT) and extend the normative data to persons older than 80 years of age.
      Participants were 92 males and 120 females with means for age and education of
      70.58 years (SD = 6.98) and 14.92 years (SD = 2.56), respectively. Normative
      information was also provided for additional measures of retention rate and
      proportion of perseverations and intrusions. The clinical utility of these norms
      strongly depends on how closely a person matches the demographic characteristics
      of the normative group.

PMID- 9240481
TI  - Gulf War veterans: a neuropsychological examination.
AB  - Eighty-two Persian Gulf War veterans seen in clinic were referred for
      neuropsychological evaluation. Relatedness of neuropsychological and neurological
      functioning to subjective complaint, exposure, a clinical signs index, and
      possible interference variables was examined in a subsample of 49 who completed
      assessment. The subsample was representative of the entire group with respect to
      symptom severity. Variables representing sustained attention, grip strength,
      motor coordination, vibratory sense, finger-tip number writing perception,
      executive functioning, memory functioning, and subjective complaint were
      considered. Neuropsychological performance appeared to be more related to
      emotional functioning than demographic variables or variables associated with the
      war. Individual differences may be contributing to different emotional reactions
      to illnesses, perceptions of exposure risks and cognitive functioning, and
      responses to stress.

PMID- 9240480
TI  - Performance of elderly White and African American community residents on the
      abbreviated CERAD Boston Naming Test.
AB  - Differences in the responses of an elderly biracial group of cognitively normal
      subjects to a 15-item short version of the Boston Naming Test developed for the
      Consortium to Establish a Registry for Alzheimer's Disease (CERAD) were examined.
      The subjects consisted of 103 Whites and 136 African Americans who were 70 years
      of age and older and living in a five-county urban and rural area of North
      Carolina. They were drawn from the Duke University site of the Established
      Populations for Epidemiologic Studies of the Elderly (EPESE). All were
      cognitively normal. With gender, years of education, and age controlled, White
      subjects performed significantly better than did African American subjects. The
      items in this test were selected to represent words with a high, medium, and low
      frequency of occurrence in English. They did not, however, show the expected
      gradation for either racial group. Medium and low frequency items were of
      comparable difficulty for the two races. Hierarchical ordering of difficulty
      would be improved with minor rearrangement of items.

PMID- 9240483
TI  - Monitoring frequency of occurrence without awareness: evidence from patients with
      Alzheimer's disease.
AB  - People are surprisingly accurate at judging how often an event occurs. Patients
      with Alzheimer's disease (AD), however, perform poorly on such tasks, suggesting
      that this ability is compromised when episodic memory is impaired. The tasks used
      to assess this ability in previous studies, however, placed demands on retrieval
      that could obscure whether frequency of occurrence was adequately encoded. We
      developed an indirect test of frequency monitoring based on changes in reading
      time as a function of item repetition. Using this procedure, patients with AD
      showed normal frequency monitoring for novel information (Turkish words) even
      though they were unable to remember the words or judge how often individual words
      had been presented. These findings suggest the existence of a mechanism that
      automatically monitors frequency of occurrence and operates outside of conscious
      awareness.

PMID- 9240484
TI  - Cognitive changes in very old persons with dementia: the influence of
      demographic, psychometric, and biological variables.
AB  - Longitudinal changes in global cognitive functioning, indexed by the Mini-Mental
      State Examination (MMSE), in subjects with dementia (Alzheimer's disease and
      vascular dementia) were examined. The roles of several demographic, psychometric,
      and biological indices in predicting cognitive deterioration were also examined.
      The sample consisted of 36 very old (M age at entry = 83.0 years, range = 75-95)
      adults with dementia from a community-based study. Subjects were tested on two
      occasions separated by approximately 2.5 years. Results indicated significant
      longitudinal decline in MMSE scores over the retest interval; the average decline
      was estimated as 2.43 (SD = 1.81) points per year. Several factors were
      associated with cognitive deterioration. Higher initial MMSE scores were
      associated with greater deterioration, whereas superior forward digit span and
      Block Design at entry were associated with attenuated decline, once differences
      in baseline severity were accounted for. By contrast, a variety of other
      putatively important variables exhibited no relationship to decline, including
      age, gender, education, onset age, dementia type, backward digit span, as well as
      a number of biological parameters (e.g., vitamin B12, folic acid). The results
      suggest that although the magnitude of cognitive deterioration in dementia is
      highly variable, several indicators may be useful predictors of future changes in
      cognitive functioning.

PMID- 9240485
TI  - Effects of medical risk and socioeconomic status on the rate of change in
      cognitive and social development for low birth weight children.
AB  - Using Hierarchical Linear Models (HLM) analysis, this study evaluated the effects
      of medical risk at birth and socioeconomic status (SES) on the rate of change in
      cognitive and social development over the first three years of life in premature
      children with low birth weight (LBW). Children with LBW (n = 79) with both high
      (HR) (n = 37) and low (LR) (n = 42) medical risk were compared to healthy full
      term (FT) (n = 49) children. Children were assessed longitudinally at 6, 12, 24,
      and 36 months for cognitive development with the Bayley Scales of Infant
      Development and the McCarthy Scales for Children's Abilities, and for social
      initiative and responsiveness with observational measures. The HR LBW group had
      slower rates of increases in cognitive scores than did the LR LBW and FT groups
      and showed more deceleration in cognitive development by 36 months of age.
      Children with LBW, regardless of medical risk, had lower social initiating scores
      and slower rates of increase in initiating across the first 36 months than did FT
      children. As predicted, the groups did not show different rates of change for
      measures of social responsiveness. Higher SES was predictive of better cognitive
      and social development for all children. The difficulties encountered by children
      with LR and HR LBW in developing social initiating skills are discussed in
      relation to the link between learning to take initiative and early executive
      function skills.

PMID- 9240486
TI  - Mild head injury and speed of information processing: a prospective study of
      professional rugby league players.
AB  - The sensitivity of several short tests of speed of information processing to the
      effects of mild head injury in rugby league football was investigated. The
      measures used were the Symbol Digit Modalities Test, the Digit Symbol
      Substitution Test, and the Speed of Comprehension Test. Two studies were
      conducted, the first to examine the effect of practice, the second to determine
      sensitivity to cognitive impairment immediately following injury. The first study
      established alternate form equivalence and demonstrated that performance on the
      Speed of Comprehension and Digit Symbol Substitution tests improved with
      practice, whereas the Symbol Digit Modalities test remained stable. A second
      study of 10 players who subsequently sustained mild head injuries showed that
      measures of speed of information processing were sensitive to impairment in the
      postacute phase, whereas an untimed task of word recognition (Spot-the-Word) was
      not. Speed of Comprehension was more sensitive to postinjury impairment than
      either the Digit Symbol Substitution or Symbol Digit Modalities tests. A repeated
      baseline assessment before injury using the higher score to reflect a player's
      potential, allowed measurement of impaired performance on sensitive tests.

PMID- 9240487
TI  - Cognitive complaints in closed-head injury: relationship to memory test
      performance and emotional disturbance.
AB  - Self-appraisal of cognitive difficulties by a sample of 63 male patients with
      closed-head injury (CHI) was examined in relation to their performance on the
      Wechsler Memory Scale - Revised (WMS-R; Wechsler, 1987), WAIS-R Digit Span
      (Wechsler, 1981), and to their scores on MMPI-2 (Butcher, Dahlstrom, Graham,
      Tellegen, & Kaemmer, 1989) measures of anxiety and depression. In an initial
      step, the Cognitive Difficulties Scale (CDS; McNair & Kahn, 1983), consisting of
      39 self-report items, was factor analyzed using a sample of 255 consecutive
      neuropsychological referrals with documented brain impairment. Seven orthogonal
      dimensions emerged: Attention and Concentration, Orientation and Memory, Praxis,
      Domestic Activities, Facial Recognition, Task Efficiency, and Errand and Name
      Recall. Within a sample subset consisting of 63 patients with CHI, subjective
      complaints on the CDS were predictive of WMS-R Logical Memory performance (r = 
      .51, p < .0005). In contrast, CDS scores were generally poor predictors of Digit
      Span and Visual Reproduction scores (rs < .31). Cognitive complaints were also
      associated with emotional distress on the MMPI-2. The CDS appears to be a useful
      measure of self-appraised cognitive difficulties in patients with CHI, and may
      assist in the assessment of their self-reflective insight.

PMID- 9240488
TI  - Examining the diagnostic utility of the Fuld cholinergic deficit profile on the
      Japanese WAIS-R.
AB  - The diagnostic utility of the Fuld cholinergic deficit profile (Fuld, 1984) to
      dementia of the Alzheimer type (DAT) was evaluated on the Japanese version of the
      WAIS-R. Profiles were calculated for groups of subjects with DAT(n = 236),
      vascular dementia (n = 29), frontotemporal dementia (n = 22), and hydrocephalic
      dementia (n = 10). The frequency of positive profile occurrence for the subject
      groups was as follows: 23/236 for DAT (9.7%), 2/29 (6.9%) for vascular dementia,
      2/22 (9.1%) for frontotemporal dementia, and 2/10 (20%) for hydrocephalic
      dementia. No significant difference in the frequency of positive profile
      occurrence was revealed across four types of dementia. We conclude from these
      findings that the Fuld profile lacks the diagnostic utility on the Japanese WAIS
      R.

PMID- 9240489
TI  - Non cholinergic toxicity of Sarin.

PMID- 9240490
TI  - Cyclophosphamide pulse therapy for rapidly progressive interstitial pneumonia in
      dermatomyositis. A new possibility for rescue?

PMID- 9240491
TI  - Relationship between changes of bone mineral content and twelve-minute walking
      distance in men with chronic obstructive pulmonary disease: a longitudinal study.
AB  - Cross-sectional studies have revealed that bone mass is reduced in patients with
      chronic obstructive pulmonary disease (COPD). To elucidate the factors
      influencing bone mass in COPD, we measured whole body bone mineral content (BMC)
      by dual energy X-ray absorptiometry (DXA), pulmonary function, and twelve-minute
      walking distance (TMD) in men with COPD, who had been monitored for at least one
      year. We studied the body composition in 22 male patients with COPD and 19 age
      matched male controls (age 72.6 +/- 7.2 vs 67.5 +/- 10.1 years, mean +/- SD).
      COPD patients showed a significantly lower body weight (49.3 +/- 5.7 vs 57.9 +/-
      3.5 kg, respectively), body mass index (18.9 +/- 2.1 vs 22.1 +/- 1.3 kg/m2) and
      BMC (1.9 +/- 0.4 vs 2.2 +/- 0.4 kg) than controls. The changes in BMC were
      significantly correlated with TMD (r=0.53, p<0.02). These results demonstrate
      that decreased exercise capacity, at least in part, accounts for acceleration of
      bone mass loss in COPD patients.

PMID- 9240492
TI  - Changes in the arterial PCO2 during a single night's sleep in patients with
      obstructive sleep apnea.
AB  - To investigate the relationship between hypercapnia during sleep and its
      influence on the PaCO2 during the morning after sleep in patients with
      obstructive sleep apnea syndrome (OSAS), the transcutaneous PCO2 (PtcCO2) was
      measured throughout the night, and the arterial blood gases (ABG) were also
      measured while awake before and after polysomnography in 30 OSAS patients with
      (n=13, hypercapnic group: HC) and without (n=17, normocapnic group: NC)
      hypercapnia. Significant differences were observed in the body mass index
      (p=0.03), the difference between the highest PtcCO2 during sleep and the PtcCO2
      during awake before sleep (D-PtcCO2), (HC: 11.l+/-1.7 mmHg; NC: 6.3+/-0.5 mmHg;
      p=0.0057) and the lowest SaO2 during sleep (p=0.0007). In the HC, the PaCO2 on
      the morning after sleep (50.0+/-0.14 mmHg) was significantly increased (p=0.0029)
      compared with the PaCO2 on the night before sleep (47.4+/-1.1 mmHg). In the NC,
      this phenomenon was not observed. Severe hypercapnia (high D-PtcCO2) during a
      single night's sleep has a significant effect on the waking PaCO2 immediately
      following sleep in the HC.

PMID- 9240493
TI  - CD8+ T lymphocyte counts as an adjunctive predictor of cytomegalovirus retinitis
      in patients with acquired immunodeficiency syndrome.
AB  - We encountered a case of cytomegalovirus (CMV) retinitis with spontaneous
      regression in association with an increased number of CD8+ but not CD4+ T
      lymphocytes in a patient with acquired immunodeficiency syndrome (AIDS). Thus, we
      examined the number of CD4 and CD8 counts at the diagnosis of CMV retinitis and
      compared with those of Pneumocystis carinii pneumonia (PCP). All 21 patients with
      a confirmed diagnosis of PCP (22 episodes) and 14 CMV retinitis patients were
      included in this study. Although PCP occurred after depletion of CD4 count to
      below 200/microl, CD8 count at that time varied widely and remained normal in
      some patients (median: 276.5/microl, range: 133-900/microl). In contrast, as CMV
      retinitis occurred after further depletion of CD4 count to below 50/microl, CD8
      count decreased to below 500/microl (median: 238/microl, range: 43-448/microl)
      (p<0.05; PCP vs CMV retinitis). The values of the sensitivity and specificity for
      CMV retinitis obtained at the cutoff point of either 400/microl in CD8 count and
      50/microl in CD4 count were similar. When these two cutoff points were combined,
      the positive predictive value was 46%. Monitoring of CD8 count may prove valuable
      as an additional predictor of CMV retinitis in patients with AIDS after CD4
      depletion.

PMID- 9240495
TI  - Chronic total occlusion of the left main coronary artery.
AB  - We report 3 patients with chronic total occlusion of the left main coronary
      artery, which is considered to be very rare. In all three cases, coronary
      arteriograms showed a total occlusion of the left main coronary artery with good
      collaterals from the intact right coronary arteries. All of the patients
      underwent successful coronary artery bypass surgery; two of the cases were
      followed up for more than 10 years after the surgery. The Japanese literature is
      reviewed, and a comparison of foreign and Japanese cases is discussed.

PMID- 9240496
TI  - Effectiveness of aldose reductase inhibitors for diabetic gastroenteropathy with
      constipation.
AB  - We present a diabetic patient with long-standing constipation complicated by
      paralytic ileus and septic shock. She successfully recovered from a critical
      condition, and her diabetes was well controlled. However, the constipation did
      not improve even after the administration of conventional medications.
      Epalrestat, an aldose reductase inhibitor (ARI), improved her bowel motility and
      autonomic cardiovascular dysfunction, as evident from her heart rate and blood
      pressure response. Gastroenteropathy is a major diabetic complication which may
      cause disturbed bowel motility leading to serious enterobacterial infections,
      thus, its amelioration is important. ARI may be beneficial in the treatment of
      diabetic gastroenteropathy refractory to conventional therapies.

PMID- 9240494
TI  - Eighteen cases exposed to sarin in Matsumoto, Japan.
AB  - Forty-six patients who were exposed to sarin consulted our hospital because of
      darkness of vision, and ocular pain, vomiting, dyspnea and headaches on June 27
      and 28, 1994. Eighteen patients were admitted and 4 of them were in the critical
      state. There were 6 features: 1) depression of plasma cholinesterase activity (17
      of 18 patients, 94%), 2) hypokalemia (4/18, 22%), 3) depression of triglyceride
      (12/18, 67%), 4) hypocapnia (5/17, 29%), 5) partial pressure of oxygen (PaO2) <80
      mmHg, or requirement of O2 inhalation (15/18, 83%), 6) white blood cells (WBC)
      >9,000 per mm3 (13/18, 72%). Seventeen patients were discharged from hospital,
      but one patient is still suffering from akinetic mutism after two years.

PMID- 9240497
TI  - Relapse in the external auditory canal of acute promyelocytic leukemia after
      treatment with all-trans retinoic acid.
AB  - A 54-year-old female was admitted to our hospital for gingival bleeding and was
      diagnosed as acute promyelocytic leukemia (APL). She received induction therapy
      according to the AML92 protocol of the Japan Adult Leukemia Study Group (JALSG)
      with all-trans retinoic acid (ATRA) plus chemotherapeutic agents. She achieved
      complete remission, but one year later had a relapse in her external auditory
      canal without leukemic cell in the bone marrow. Extramedullary disease is rare in
      APL. This case suggests the importance of careful observation for extramedullary
      relapse in patients who are treated with ATRA.

PMID- 9240498
TI  - Apheresis therapy for prolonged red cell aplasia after major ABO-mismatched bone
      marrow transplantation.
AB  - Two cases of leukemia were treated successfully with apheresis for delayed
      recovery of erythropoiesis due to antibody-mediated red cell aplasia after ABO
      mismatched bone marrow transplantation (BMT). A 25-year-old female (ABO group O)
      underwent BMT from her brother (group A). Immunoadsorption using Biosynsorb A
      performed on day 146 after BMT followed by double filtration plasma pheresis
      (DFPP) reduced anti-A antibody titers from 1:32 to 1:2. Anemia improved
      dramatically within 2 weeks. A 49-year-old female (group O) underwent BMT from
      her mother (group A). She was treated with DFPP on day 131 after BMT. Anti-A
      antibody titers dropped from 1:16 to 1:1 and anemia improved gradually.

PMID- 9240499
TI  - Creutzfeldt-Jakob disease associated with autonomic nervous system dysfunction in
      the early stage.
AB  - A 54-year-old man presented with tremor and unusual behavior. He was admitted two
      months later because of dementia and myoclonus. Periodic synchronous discharges
      were observed on the electroencephalogram. Based on these findings, we diagnosed
      the case as Creutzfeldt-Jakob disease. About two weeks after admission,
      decubitus, bowel dysfunction and hypohidrosis occurred. We observed various
      autonomic nervous system dysfunctions such as abnormal pupillary response to
      autonomic drugs, reduced coefficient of variation of R-R interval, and abnormal
      diurnal blood pressure variation.

PMID- 9240500
TI  - Plasma levels of brain natriuretic peptide as an index for evaluation of cardiac
      function in female gene carriers of Duchenne muscular dystrophy.
AB  - The level of plasma brain natriuretic peptide (BNP) was elevated in 8 of 15
      female gene carriers of Duchenne muscular dystrophy (DMD), and the level
      correlated with indices of cardiac function. In one of these carriers, whose
      clinical course was followed for one year, the plasma BNP level was elevated
      before the development of cardiac symptoms, further increased with the evolution
      of cardiac symptoms, and then decreased after treatment for cardiac failure.
      These results suggest that the plasma BNP level may be useful for the early
      detection of cardiac dysfunction and for evaluating the efficacy of cardiac
      treatment in female DMD carriers.

PMID- 9240501
TI  - Pressure palsy as the initial presentation in a case of late-onset Charcot-Marie
      Tooth disease type 1A.
AB  - We report siblings of late-onset Charcot-Marie-Tooth disease type 1A (CMT1A) of
      whom the elder brother presented with drop foot. DNA analysis confirmed the
      17p11.2-p12 duplication. Estimation of the age of onset is difficult in CMT1A
      because of the subtle and slow progress of the symptoms. These cases are unique
      in that the initial clinical manifestation was a pressure palsy in the brother
      and both siblings were quite delayed in their clinical presentations. The
      peripheral myelin protein-22 gene duplication is uniformly found in CMT1A
      patients. However, other factors influencing the disease manifestations are yet
      to be determined.

PMID- 9240502
TI  - Cavernous angioma with olivary hypertrophy and contralateral cerebellar
      diaschisis.
AB  - We describe a 66-year-old man with a 20-year history of ataxic gait who suddenly
      developed diplopia on rightward gaze. Neurologic examination revealed right hemi
      ataxia and hemi-hypesthesia, and left internuclear ophthalmoplegia. MRI showed a
      cavernous angioma in the left tectum, mild right cerebellar atrophy, and left
      interior olivary hypertrophy. Single photon emission computed tomography (SPECT)
      imaging demonstrated contralateral cerebellar diaschisis. We discuss the findings
      and review the literature concerning contralateral cerebellar diaschisis.

PMID- 9240503
TI  - Myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibodies -- related
      scleroderma renal crisis treated with double-filtration plasmapheresis.
AB  - A 46-year-old female patient who was diagnosed with systemic sclerosis (SSc)
      developed rapidly progressive renal failure without elevation of blood pressure
      or plasma renin concentration. Renal biopsy revealed necrotizing crescentic
      glomerulonephritis (pauci-immune type) and the myeloperoxidase-specific anti
      neutrophil cytoplasmic autoantibodies (MPO-ANCA) titer was found to be elevated
      to 669 EU/ml. Methylprednisolone (MP) pulse therapy followed by prednisolone
      (PSL) and mizoribine (MZR) did not suppress the progression of renal failure.
      Therefore, we started double-filtration plasmapheresis (DFPP) which effectively
      removed MPO-ANCA and prevented renal failure despite the relatively low dose of
      immunosuppressive agents.

PMID- 9240504
TI  - Wegener's granulomatosis with dural involvement as the initial clinical
      manifestation.
AB  - We treated a patient with an atypical presentation of Wegener's granulomatosis
      (WG) with dural involvement as the initial clinical manifestation. A 37-year-old
      man had a dural lesion without lower respiratory tract or renal manifestations in
      the initial clinical course. His only initial symptom was headache, and at
      disease onset computed tomography (CT) and magnetic resonance imaging (MRI) of
      the head revealed bilateral abnormal subdural masses. The diagnosis of WG was
      made based on the results of needle biopsy of the nasal polyps and the finding of
      positive circulating antineutrophil cytoplasmic antibodies (c-ANCA). He achieved
      remission on daily prednisone and cyclophosphamide with the later addition of
      sulfamethoxazole-trimethoprim.

PMID- 9240505
TI  - Rapidly progressive interstitial lung disease associated with dermatomyositis
      responding to intravenous cyclophosphamide pulse therapy.
AB  - Interstitial lung disease, especially the rapidly progressive type, carries a
      grave prognosis when associated with polymyositis (PM)/dermatomyositis (DM). We
      describe a case of rapidly progressive interstitial lung disease associated with
      DM. Pathological findings included bronchiolitis obliterans organizing pneumonia
      (BOOP) pattern in the right upper lung lobe and interstitial fibrosis with
      microscopic honeycomb lesions in the right lower lung lobe. The patient's
      respiratory distress was severe and persistent, and oral intubation with
      mechanical ventilation was transitionally introduced. The respiratory distress
      condition responded to intravenous cyclophosphamide pulse therapy.

PMID- 9240506
TI  - Polyangiitis overlap syndrome.
AB  - A 33-year-old man was admitted to our hospital because of intermittent
      claudication and finger tip ulceration with a skin rash on the upper and lower
      extremities. He later developed a massive melena. Angiography revealed arterial
      occlusion in the hand and foot, skin biopsy showed vasculitis with eosinophilic
      infiltration, and biopsy of the colon showed mucosal vasculitis with thrombosis.
      A diagnosis of polyangiitis overlap syndrome was made, and all these symptoms
      improved after corticosteroid therapy.

PMID- 9240507
TI  - Antiphospholipid syndrome complicated by thrombosis of the superior mesenteric
      artery, co-existence of smooth muscle hyperplasia.
AB  - A 37-year-old woman underwent an emergency operation at our hospital because of
      severe abdominal pain and ileus. Most of her small intestine and ascending colon
      were observed to have become necrotic due to occlusion of her superior mesenteric
      artery (SMA). Pathological findings of the resected intestine revealed that her
      SMA was completely thrombosed 2 cm distal from its origin with smooth muscle
      proliferation. Post-surgical blood analysis of her pre-operative serum was
      positive for lupus anticoagulant and antinuclear antibodies. She noticed vaginal
      bleeding due to missed abortion on the 31st day after the operation. We diagnosed
      her acute abdominal pain to be that of antiphospholipid syndrome associated with
      her pregnancy.

PMID- 9240508
TI  - Optic neuropathy from thiamine deficiency.

PMID- 9240509
TI  - Perspectives: on the accuracy of prophecies.

PMID- 9240510
TI  - Adverse reactions to radiopharmaceuticals: the RSNA-SNM-USP Drug Product Problem
      Reporting Program.

PMID- 9240511
TI  - Urography into the 21st century: new contrast media, renal handling, imaging
      characteristics, and nephrotoxicity.

PMID- 9240512
TI  - Who will determine the direction of medical practice: physicians, patients, or
      "the market"?

PMID- 9240513
TI  - Definitive diagnosis of intramural hematoma of the thoracic aorta with MR
      imaging.

PMID- 9240514
TI  - Taking the X out of histiocytosis X.

PMID- 9240515
TI  - Nonfatal adverse reactions to iodinated contrast media: spontaneous reporting to
      the U.S. Food and Drug Administration, 1978-1994.
AB  - PURPOSE: To identify any changes in the frequency of serious, nonfatal adverse
      drug events (ADEs) reported to the U.S. Food and Drug Administration in 1978-1994
      since the introduction of low-osmolality contrast media (LOCM). MATERIALS AND
      METHODS: Reports of ADEs submitted were reviewed for use of iodinated contrast
      media. RESULTS: The estimated 170 million contrast medium-enhanced radiologic
      studies performed in 1978-1994 produced 22,785 reports of mild or moderate ADEs,
      2,639 reports of serious but nonfatal ADEs, and 920 reports of death. The most
      common ADEs (urticaria, dyspnea, vomiting, pruritus, facial edema, and
      hypotension) ranked similarly for ionic and nonionic contrast media. High
      osmolality contrast media were associated with 512 serious, nonfatal ADEs
      reported in 1978-1986; 1,068 were reported in 1987-1994. Nonionic LOCM were
      associated with 17 serious, nonfatal ADEs reported in 1978-1986; 609 were
      reported in 1987-1994. Intrathecal injection of nonionic contrast media was
      associated with 235 reported serious, nonfatal ADEs; intrathecal ionic
      [corrected] contrast media were associated with 14 such reported ADEs.
      CONCLUSION: Reports of serious, nonfatal ADEs are uncommon relative to the use of
      contrast media. The authors observed no decrease in the number of ADEs reported
      since the introduction of LOCM but did not consider marketing trends or secular
      reporting trends.

PMID- 9240516
TI  - Deaths related to iodinated contrast media reported spontaneously to the U.S.
      Food and Drug Administration, 1978-1994: effect of the availability of low
      osmolality contrast media.
AB  - PURPOSE: To determine whether reports of iodinated contrast medium-related deaths
      have decreased since low-osmolality contrast media (LOCM) became widely available
      in the United States. MATERIALS AND METHODS: With use of reports to the U.S. Food
      and Drug Administration Spontaneous Reporting System, data on iodinated contrast
      medium-related deaths after LOCM became available (1987-1994) were compared with
      data on deaths in the period before (1978-1986) and with data on deaths in an
      even earlier period (1967-1977). RESULTS: In 1967-1994, more than 1,000 contrast
      medium-related deaths were reported, 850 occurring during 1978-1994. Excluding 22
      myelography-related deaths, 37% [corrected] more deaths were reported each year
      in 1987-1994 than in 1978-1986. Most of this increase was associated with the use
      of nonionic contrast media. In 1966-1977, 228 deaths were reported; in 1978-1986,
      376; and in 1987-1994, 474. In 1987-1994, 220 deaths were associated with use of
      high-osmolality contrast media alone, 32 with ionic LOCM alone, 214 with nonionic
      LOCM alone, and eight with combinations of contrast media. CONCLUSION: Despite
      the availability of LOCM in the United States, data for 1978-1994 do not show a
      marked decrease in contrast medium-related deaths. Since 1990, more deaths have
      been associated with LOCM than with conventional contrast media. Although these
      data have substantial limitations, they shed some light on contrast medium use
      and safety.

PMID- 9240517
TI  - Common carotid artery: variability of Doppler US velocity measurements.
AB  - PURPOSE: To determine if Doppler ultrasound (US) measurements of systolic
      velocity in the common carotid artery vary markedly with distance from the
      bifurcation. MATERIALS AND METHODS: Bilateral, insonation angle-corrected
      velocity was measured with US in the common carotid artery. Measurements were
      obtained 1, 2, 3, 4, and 5 cm from the carotid artery bifurcation in 20
      volunteers (aged 25-43 years) with no history of neurologic or cardiovascular
      disease. RESULTS: Velocity in the common carotid artery increased with distance
      (toward the aorta) from the bifurcation (mean increase, 9 cm/sec for each
      centimeter of distance from the bifurcation, up to the 4-cm distance; P < .001).
      Velocity increased more rapidly in subjects who were younger (P < .001) and in
      those with a lower pulse rate (P = .001). CONCLUSION: The distance from the
      bifurcation at which common carotid artery velocity is measured should be
      standardized. This may increase the accuracy of the systolic velocity ratio for
      assessment of internal carotid artery stenosis and decrease some of the reported
      variability between different centers that perform US of the carotid artery.

PMID- 9240518
TI  - Upper extremity central venous obstruction in hemodialysis patients: treatment
      with Wallstents.
AB  - PURPOSE: To determine the effectiveness of using Wallstents to treat subclavian
      or brachiocephalic venous obstruction after unsuccessful angioplasty, in patients
      undergoing hemodialysis. MATERIALS AND METHODS: Dialysis records, radiology
      reports, and procedural images of 20 hemodialysis patients who underwent
      Wallstent insertion into a subclavian (n = 11) or brachiocephalic (n = 9) vein
      were reviewed. Technical success and primary, assisted primary, and cumulative
      patency rates were calculated. RESULTS: Twenty-three Wallstents were inserted for
      stenosis (n = 18) or occlusion (n = 2). Technical success was 100%. Eight
      patients underwent 11 reinterventions to maintain patency of the Wallstent during
      the follow-up period. Patency rates of the Wallstent were (a) primary at 1 month,
      3 months, 6 months, and 1 year: 90%, 67%, 42%, and 25%; (b) assisted primary at 3
      months, 6 months, and 1 year: 88%, 62%, and 47%; and (c) cumulative at 3 months,
      6 months, 1 year, and 2 years: 89%, 64%, 56%, and 22%. Considerable shortening of
      the stent occurred in five patients. One occurred immediately during the
      deployment procedure, but four were discovered weeks to months later. No other
      complications occurred. CONCLUSION: After suboptimal angioplasty, treatment of
      subclavian and brachiocephalic vein stenoses with a Wallstent can provide
      continued use of a hemodialysis access. Close clinical surveillance and multiple
      reinterventions are necessary to maintain Wallstent patency.

PMID- 9240519
TI  - Intramural hematoma of the thoracic aorta: MR image findings and their prognostic
      implications.
AB  - PURPOSE: To evaluate magnetic resonance (MR) imaging findings of intramural
      hematoma of the thoracic aorta and their relationship to prognosis. MATERIALS AND
      METHODS: MR images of 22 patients with intramural hematoma of the thoracic aorta
      were reviewed retrospectively. Site, thickness, degree of mural involvement, and
      signal intensity on spin-echo (SE) and cine gradient-echo (GRE) images of the
      hematoma were noted. MR findings of patients who did and those who did not
      develop complications were compared. RESULTS: Hematoma site was the only MR
      finding that correlated significantly with patient outcome. Complication
      frequencies in four (80%) of five patients with hematoma of the ascending aorta
      (type A) and in two (12%) of 17 patients with hematoma of the descending aorta
      (type B) were significantly different (P = .009). There were moderately strong
      correlations between days after symptom onset and signal intensity of the
      hematoma on SE (r = 0.78) and GRE (r = 0.72) images. MR images of two of three
      patients who developed early-subacute complications showed signal intensity
      changes of the hematoma that were consistent with recurrent bleeding. CONCLUSION:
      Patients with MR findings consistent with type A intramural hematoma of the
      thoracic aorta should undergo surgery. In cases of type B intramural hematoma of
      the thoracic aorta, MR imaging can be useful for detecting complete resolution or
      impending complications of the hematoma.

PMID- 9240520
TI  - Evaluation of the aortoiliac and renal arteries: comparison of breath-hold,
      contrast-enhanced, three-dimensional MR angiography with conventional catheter
      angiography.
AB  - PURPOSE: To determine the diagnostic accuracy of breath-hold, contrast material
      enhanced, three-dimensional (3D) magnetic resonance (MR) angiography in the
      assessment of the aortoiliac inflow tract and renal arteries with conventional
      catheter angiography as the standard of reference. MATERIALS AND METHODS: In 39
      patients with symptomatic peripheral vascular disease, both catheter and contrast
      enhanced, 3D MR angiography were performed. In a prospective blinded analysis,
      each vascular segment (23 segments per arterial tree) was evaluated for the
      presence of obstructive stenosis, graded as mild (<50%), severe (50%-99%), or
      occlusion (100%), as well as for aneurysmal disease. RESULTS: Obstructive (n = 2)
      and aneurysmatic aortic (n = 6) lesions and 10 of 11 accessory renal arteries
      were identified and graded correctly with MR angiography. For detection of
      hemodynamically significant stenotic lesions (>50%) or occlusions with MR
      angiography, sensitivity and specificity, respectively, were 93% and 98% for the
      renal arteries, 96% and 100% for the common iliac arteries, 93% and 93% for the
      external iliac arteries, and 96% and 94% for the internal iliac arteries.
      CONCLUSION: The diagnostic performance of contrast-enhanced 3D MR angiography is
      comparable with that of catheter angiography and thus may contribute to
      assessment of the aorta, the renal arteries, and the pelvic arterial system in
      patients with peripheral vascular disease before they undergo therapy.

PMID- 9240521
TI  - In vitro cytotoxicity of silver-impregnated collagen cuffs designed to decrease
      infection in tunneled catheters.
AB  - PURPOSE: To examine in vitro the effects of silver-impregnated collagen cuff
      material from central venous catheters on human fibroblast growth. MATERIALS AND
      METHODS: In culture flasks, hybrid cells were exposed to silver-impregnated
      collagen cuff material, and human fibroblasts were exposed to silver-impregnated
      or silver-free collagen cuff material. After 72 hours of growth, cells were
      stained and digitally imaged, and the relative areas of cytotoxicity were
      determined. RESULTS: Flasks containing the silver-impregnated collagen cuff
      material and hybrid cells or human fibroblasts showed a marked local cytotoxic
      effect of the cuff material; cell-free zones surrounding the cuff material were
      demonstrated. No cytotoxic effect was seen in the flasks that contained silver
      free cuff material (control group). Mean area of cleared cells was 312 mm2 +/-
      130 (range, 156-624 mm2) in the flasks containing human fibroblasts and silver
      impregnated cuff material and 0 mm2 in the corresponding control flasks (P <
      .0001). Mean radius of the area of cleared cells around the silver-impregnated
      cuff material in the flasks containing human fibroblasts was 9.8 mm +/- 2.0
      (range, 7.0-14.1 mm). CONCLUSION: Silver-impregnated collagen cuff material
      demonstrates a local cytotoxicity on hybrid cells and human fibroblasts in vitro.
      This finding may explain the phenomena seen clinically of decreased anchorage and
      inadvertent removal of catheters with silver-impregnated collagen cuffs.

PMID- 9240522
TI  - Transjugular liver biopsy with an automated device.
AB  - PURPOSE: To determine the potential for use of an automated device for
      transjugular liver biopsy. MATERIALS AND METHODS: In 29 consecutive patients with
      liver dysfunction in whom percutaneous transperitoneal biopsy was contraindicated
      because of thrombocytopenia, severe coagulopathy, or marked ascites, transjugular
      liver biopsy was performed with an 18-gauge automated device. Histopathologic
      specimens were quantitatively and qualitatively analyzed. Complications related
      to the biopsy procedure were noted. RESULTS: In all patients, an adequate biopsy
      specimen (mean length, 12.0 mm +/- 5.5; range, 5.0-20.0 mm) was obtained during a
      single pass. In all tissue samples, a confident histopathologic diagnosis was
      made. Additional information was obtained in 15 patients with cirrhosis who had
      coexisting diffuse hepatic disease. No complications related to the procedure
      were noted. CONCLUSION: Use of an automated biopsy device is recommended for
      transjugular liver biopsy, as it enables safe acquisition of high-quality hepatic
      tissue samples.

PMID- 9240523
TI  - Myocardial perfusion reserve: assessment with multisection, quantitative, first
      pass MR imaging.
AB  - PURPOSE: To demonstrate the feasibility of determining myocardial blood flow
      changes and the myocardial perfusion reserve with magnetic resonance (MR) first
      pass imaging, to validate the MR results by means of comparison with radiolabeled
      microsphere flow measurements in an animal model, and to compare the coronary
      flow reserve with the perfusion reserve at MR imaging in patients with
      hemodynamically nonsignificant coronary lesions and angina. MATERIALS AND
      METHODS: Arrhythmia-insensitive, first-pass, multisection, T1-weighted MR imaging
      with contrast agent enhancement was performed in eight pigs with acute ischemia
      and in eight adult patients (six women, two men). In the pigs, microsphere flow
      measurements were obtained in parallel with the MR measurements. In the patients,
      the coronary flow reserve was measured with an intracoronary Doppler flow
      ultrasound probe for comparison with the MR perfusion reserve. RESULTS: In the
      animal studies, there was linear correlation between MR perfusion indexes and the
      microsphere flow measurements (r = .88, P < .01). In the patients, the regional
      perfusion reserve matched the coronary flow reserve (linear regression with a
      slope of 1.02 +/- 0.09, r = .80). CONCLUSION: The myocardial perfusion reserve
      can be quantified with first-pass MR imaging. In patients with microvascular
      dysfunction, the myocardial perfusion reserve matches the reduced coronary flow
      reserve.

PMID- 9240524
TI  - Subpleural sparing: a CT finding of lung contusion in children.
AB  - PURPOSE: To evaluate the presence of subpleural sparing as an aid in
      differentiation of contusion from other causes of lung opacification in children.
      MATERIALS AND METHODS: In 29 children, the computed tomographic (CT) features of
      40 lung contusions were reviewed for the presence of subpleural sparing. Other CT
      characteristics of lung contusion such as location, shape, and confluence were
      also evaluated. The presence of subpleural sparing was also evaluated in cases of
      atelectasis, pulmonary laceration, and a control group of CT scans obtained in 45
      patients with bacterial pneumonia and no history of trauma. RESULTS: Subpleural
      sparing was seen at CT in 38 (95%) of the lung contusions and none of the cases
      of atelectasis, laceration, or pneumonia (P = .0001). Lung contusions tended to
      be posterior (60%), crescentic (50%), or amorphous (45%) and have confluent and
      nodular components (70%). CONCLUSION: The presence of subpleural sparing on CT
      scans enables accurate identification of lung contusion and differentiation of
      contusion from other causes of lung opacification in children after trauma.

PMID- 9240525
TI  - Normal pediatric testis: comparison of power Doppler and color Doppler US in the
      detection of blood flow.
AB  - PURPOSE: To compare power Doppler and conventional color Doppler ultrasound (US)
      in the detection of blood flow in the normal pediatric testis and to assess the
      symmetry of blood flow and the spectral Doppler tracing waveforms in the normal
      pediatric testis. MATERIALS AND METHODS: Testicular blood flow was assessed
      prospectively in 68 testes in 34 boys (age range, 6 weeks to 13 years; mean age,
      4.6 years) with both conventional color and power Doppler US. Intratesticular
      blood flow was graded as follows: 0, no intratesticular flow; 1, single
      intratesticular Doppler signal identified; and 2, multiple intratesticular
      Doppler signals identified. The symmetry of intratesticular flow was assessed
      both subjectively and objectively by using the same grading system. Spectral
      Doppler tracings were obtained in 62 testes in 31 patients. RESULTS: Power
      Doppler US demonstrated intratesticular blood flow in 66 (97%) testes. Color
      Doppler US demonstrated intratesticular blood flow in 60 (88%) testes. Combined
      techniques depicted blood flow in all 68 (100%) testes. Testicular blood flow was
      judged symmetric in all 34 (100%) patients with power Doppler US and in 31 (91%)
      patients with color Doppler US. Spectral Doppler tracings demonstrated absence of
      diastolic flow in 20 (32%) of 62 testes. CONCLUSION: In children, power Doppler
      US is more sensitive than color Doppler US in the detection of intratesticular
      blood flow. With power Doppler US, testicular blood flow in healthy children is
      symmetric, underscoring that the asymptomatic testis can be used as a baseline
      for assessing flow in the symptomatic testis.

PMID- 9240526
TI  - Knee and shoulder fractures: association of fracture detection and marrow edema
      on MR images with mechanism of injury.
AB  - PURPOSE: To assess the value of magnetic resonance (MR) imaging for enabling the
      classification of fracture mechanisms and to compare marrow edema caused by
      compressive forces with that caused by tensile forces. MATERIALS AND METHODS: In
      62 knees or shoulders, 78 fractures were identified prospectively on MR images or
      plain radiographs; compressive or tensile forces were determined retrospectively
      to have caused impaction or distraction fractures, respectively. Edema was
      measured on T1-weighted images. Frequencies of fracture detection on MR images or
      plain radiographs were compared. RESULTS: Forty-nine (63%) and 29 (37%) fractures
      were attributed to compressive and tensile forces, respectively. Edema measured
      31 mm +/- 10 in impaction fractures and 2.5 mm +/- 2.4 in distraction fractures
      (P < .001). MR images and plain radiographs of 63 fractures were compared. On MR
      images, distraction fractures, including four of seven Segond fractures, were
      missed more often than impaction fractures (P < .008). Fractures overlooked on MR
      images were associated with less edema (P < .003). CONCLUSION: On MR images,
      impaction fractures demonstrate prominent marrow edema, and distraction fractures
      demonstrate minimal edema. Impaction fractures are more often missed on plain
      radiographs, and distraction fractures are more often missed on MR images. Segond
      fractures should be suspected if MR images show lateral capsular ligamentous
      injury in the knee; in these cases, evaluation with plain radiography is
      warranted.

PMID- 9240527
TI  - Total creatine in muscle: imaging and quantification with proton MR spectroscopy.
AB  - PURPOSE: To provide a noninvasive method of imaging and quantifying total
      creatine (phosphorylated plus unphosphorylated) in human muscle with proton
      magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Water-suppressed,
      long echo time, stimulated-echo hydrogen-1 chemical shift imaging and short echo
      time unsuppressed chemical shift imaging were performed on the lower legs of 10
      healthy volunteers at rest. Spatial resolution was 4.5-8.0 cm3. Water signals in
      unsuppressed data sets were quantified and used as chemical shift and
      concentration references. Images of the integrated N-CH3 resonance assigned to
      total creatine were extracted from the water-suppressed chemical shift image
      data. Correlations between the total creatine, lipid, and water signals from the
      same voxels were tested. The concentration of total creatine in skeletal muscle
      was calculated from the ratio of the relaxation-corrected N-CH3 and water signals
      from the same voxels. RESULTS: Total creatine was localized to muscle bundles.
      Lipid signals contributed less than 6% to the variance of total creatine signal
      on images and in measurements and did not correlate with total creatine in the
      same voxels (P > .1). Total creatine and unsuppressed water signals were
      positively correlated (P < .0001). MR spectroscopy yielded a total creatine value
      of 36.2 mmol/kg wet weight +/- 5.0, consistent with prior biopsy data.
      CONCLUSION: H-1 MR spectroscopy can be used to image and noninvasively quantify
      total creatine in human muscle. Its use could improve the understanding of the
      role of altered creatine metabolism in muscle disease and aid quantification of
      the response to creatine therapies.

PMID- 9240529
TI  - Paramagnetic metal scavenging by melanin: MR imaging.
AB  - PURPOSE: To quantitate the binding of metals to synthetic melanin in vitro, which
      is believed to be the reason why melanotic melanomas are hyperintense on T1
      weighted magnetic resonance (MR) images, and to test whether such binding by
      natural melanin can be detected in cultured melanoma cells in vivo with MR
      imaging. MATERIALS AND METHODS: Seven synthetic metallomelanins were prepared and
      their metal contents and relaxivities determined. Melanotic PC1A and amelanotic
      B16 melanoma cells were incubated with increasing concentrations of iron. MR
      images of synthetic melanin and cell phantoms were obtained. RESULTS: The iron
      binding capacities and relaxivities of the different synthetic metallomelanins
      varied considerably, which reflects the heterogeneous structure of melanin and
      the complexity of its binding of metals. Nevertheless, the MR signal intensities
      of the synthetic melanin and cell phantoms show marked increases that scale,
      respectively, with increasing iron content and iron concentration in the
      incubation medium. CONCLUSION: Melanotic melanomas are hyperintense on T1
      weighted images because of paramagnetic metal scavenging. This observation has
      implications for the interpretation of MR images, the improved detection of
      melanomas, and the development of imaging marker genes.

PMID- 9240528
TI  - Fluoroscopically guided injections into the foot and ankle: localization of the
      source of pain as a guide to treatment--prospective study.
AB  - PURPOSE: To determine the value of injections of local anesthetic and steroids in
      the foot and ankle in localizing the source of pain and their effect on clinical
      confidence and decision making. MATERIALS AND METHODS: In 47 patients,
      fluoroscopically guided injections of local anesthetic and steroid into the foot
      and ankle were performed in 106 intra- and extraarticular sites. Questionnaires
      were completed by the referring surgeon before and after injections to evaluate
      the level of confidence with regard to the source of pain for each site injected
      and the proposed treatment plan. RESULTS: Forty-three (91%) patients reported
      pain relief after injections. The level of confidence that the site injected was
      the source of pain increased in 68 (64%) sites, decreased in 19 (18%) sites, and
      remained unaltered in 19 (18%) sites (P < .01). The treatment plan was changed
      from nonsurgical initially to surgical in three (8%) of 36 patients and was
      changed from surgical to nonsurgical in three (27%) of 11 patients after
      injections. Of the remaining eight patients, treatment was altered in three (37%)
      as a result of pain relief after the injections. CONCLUSION: Fluoroscopically
      guided injections of local anesthetic and steroid in the foot and ankle can
      improve clinical confidence with regard to the site of pain and may be valuable
      in clinical decision making and patient treatment.

PMID- 9240530
TI  - MR imaging and scintigraphy of gene expression through melanin induction.
AB  - PURPOSE: To determine whether an expression vector that encodes for human
      tyrosinase, the key enzyme in the melanin production pathway, can be used to
      image gene expression with magnetic resonance (MR) imaging and scintigraphy.
      MATERIALS AND METHODS: Mouse fibroblasts and human embryonal kidney cells were
      transfected with an expression vector that contained a complete complementary DNA
      sequence that encodes the human tyrosinase gene (pcDNA3tyr). Transfected cells
      were assayed for messenger RNA presence, melanin staining, and indium-111
      binding; scintigraphy and MR imaging were performed. RESULTS: Transfected cells
      contained tyrosinase messenger RNA and stained positively for melanin.
      Transfected cells had a higher In-111 binding capacity than nontransfected cells,
      a difference readily detectable with scintigraphy. MR imaging showed transfected
      cells to have markedly higher signal intensity after gene transfer than
      nontransfected cells. CONCLUSION: Gene transfer and expression in cell culture
      can be detected with MR imaging and scintigraphy. The proposed strategy of using
      an imaging marker gene may have a substantial effect on the noninvasive imaging
      of gene therapy.

PMID- 9240531
TI  - Primary non-Hodgkin lymphoma of the sinonasal cavities: correlation of CT
      evaluation with clinical outcome.
AB  - PURPOSE: To determine retrospectively the primary site of origin of sinonasal
      lymphomas with computed tomography (CT) and correlate the CT findings with
      histologic phenotype and clinical outcome. MATERIALS AND METHODS: In 24 patients
      with stage I and II non-Hodgkin lymphomas of the sinonasal cavities, the CT
      appearances and clinical data were reviewed retrospectively. RESULTS: The sites
      of primary tumor determined at CT were the nasal cavity in 13 patients, the
      ethmoidal sinus in three patients, and the maxillary sinus in eight patients. B
      cell lymphomas were found mainly in the maxillary sinus, while T-cell lymphomas
      were found in the nasal cavity and ethmoidal sinus (P < .005). The 5-year
      survival rates in relation to the primary site of the tumor were 64% for the
      nasal cavity, 50% for the ethmoidal sinus, and 100% for the maxillary sinus (P =
      .26). CONCLUSION: Patients with B-cell primary lymphoma of the maxillary sinus
      tended to have a good prognosis in contrast to those with T-cell lymphomas that
      originated from midline structures. The primary site determined at CT appears to
      be correlated with the histologic phenotype and clinical outcome.

PMID- 9240532
TI  - Salivary gland stones: US evaluation in shock wave lithotripsy.
AB  - PURPOSE: To assess the usefulness of ultrasonography (US) in the selection and
      monitoring of patients with sialolithiasis to be treated with extracorporeal
      electromagnetic shock wave lithotripsy. MATERIALS AND METHODS: US was performed
      in 80 symptomatic outpatients who were to undergo shock wave lithotripsy because
      they were not candidates for endoral extraction of calculi. The location and
      diameter of stones and the condition of the affected gland and duct were
      determined. RESULTS: Swollen and sclerotic glands and dilated ducts were the most
      frequently observed characteristics. After lithotripsy, stone clearance or a
      residual fragment of less than 2 mm in diameter was seen at US in 37 of 56
      patients with submandibular gland calculi and in all 24 patients with parotid
      gland calculi. Favorable outcome after lithotripsy was associated with smaller
      (less than 7 mm) stone diameter (P < .001) and, in the case of submandibular
      gland stones, with intraductal location (P < .05). A return to a normal
      parenchymal echotexture was seen in all patients in whom the stone was completely
      eliminated; a limited reduction in swelling was observed in patients with
      residual fragments. CONCLUSION: US is useful in the selection of candidates for
      extracorporeal electromagnetic shock wave lithotripsy and in monitoring the
      progress of treatment.

PMID- 9240533
TI  - Who performs neuroimaging? Results from the 1993 National Medicare Database.
AB  - PURPOSE: To determine the level of participation of nonradiologists in computed
      tomography (CT) and magnetic resonance (MR) imaging of the brain, head and neck,
      and spine at hospitals and at private offices and imaging centers in the United
      States. MATERIALS AND METHODS: The 1993 Part B Medicare Annual Database was used
      to determine the number of procedures performed by radiologists and
      nonradiologists at hospitals and at private offices or imaging centers. The
      fourth edition of the Physicians' Current Procedural Terminology was used to
      classify procedures. RESULTS: Of the 3,883,391 neurologic CT and MR imaging
      studies billed to Medicare in 1993, 3,148,088 (81%) were obtained in a hospital
      setting; only 58,005 (2%) of these studies were interpreted by nonradiologists.
      Of the 735,303 imaging studies (19%) obtained at a private office or imaging
      center, only 63,115 (9%) studies were interpreted by nonradiologists. Overall,
      nonradiologists performed only 121,120 (3%) of the neuroimaging examinations
      billed to Medicare nationwide in 1993. CONCLUSION: The level of participation of
      nonradiologists in the interpretation of results from neurologic CT and MR
      imaging billed to Medicare is minimal.

PMID- 9240534
TI  - Rapid MR imaging versus plain radiography in patients with low back pain: initial
      results of a randomized study.
AB  - PURPOSE: To demonstrate the feasibility of a randomized trial to compare rapid
      magnetic resonance (MR) imaging with plain radiography as the initial imaging
      study in patients with low back pain, to test measures of the decision-making
      process and patient outcomes, and to offer a model for using randomized clinical
      trials to evaluate diagnostic tests. MATERIALS AND METHODS: The authors randomly
      selected 62 patients with low back pain to undergo either rapid MR imaging or
      plain radiography. The authors measured functional status, satisfaction, and
      general health status at baseline and at 3 months. The modified Roland scale was
      the primary outcome measure. In addition, the authors examined diagnostic and
      therapeutic decision making and resources used by each group. RESULTS: There were
      no statistically significant differences between the two patient groups with
      respect to outcome (Roland score: MR imaging = 12.5, radiography = 12.1). MR
      imaging provided more useful information to clinicians and resulted in greater
      patient reassurance. CONCLUSION: Randomly selecting patients to undergo imaging
      examinations and measuring outcomes is feasible; however, a larger, multicenter
      study is necessary to determine whether rapid MR imaging is a cost-effective
      replacement for plain radiography in patients with low back pain.

PMID- 9240535
TI  - Trigeminal neuralgia: comparison of two MR imaging techniques in the
      demonstration of neurovascular contact.
AB  - PURPOSE: To compare two magnetic resonance (MR) imaging techniques for
      demonstration of vascular contact with the trigeminal nerve. MATERIALS AND
      METHODS: Thirteen patients with unilateral trigeminal neuralgia and 50 control
      subjects underwent three-dimensional fast inflow with steady-state precession
      (FISP) and contrast material-enhanced magnetization-prepared rapid acquisition
      gradient-echo (MP-RAGE) MR imaging. The images were independently reviewed by two
      neuroradiologists, who were blinded to the clinical details. Six of the 13
      patients underwent surgery. RESULTS: Vascular contact with the trigeminal nerve
      at the root entry zone was seen on FISP images in 10 of 13 (77%) symptomatic
      nerves and in eight of 113 (7%) asymptomatic nerves (P < .001). MP-RAGE and FISP
      images demonstrated arterial contacts equally well. MP-RAGE images demonstrated
      one additional venous contact at the root entry zone in a patient with
      ipsilateral trigeminal neuralgia. Interobserver agreement was good for both FISP
      (kappa = 0.69) and MP-RAGE (kappa = 0.78) images. The presence of vascular
      contact at the root entry zone, seen on preoperative MR images, was confirmed in
      all six patients who underwent surgery. CONCLUSION: Both FISP and MP-RAGE MR
      imaging are useful in demonstrating vascular contact with the trigeminal nerve at
      the root entry zone in patients with trigeminal neuralgia.

PMID- 9240536
TI  - Intracranial meningiomas: factors that influence the development of cerebral
      edema after stereotactic radiosurgery and radiation therapy.
AB  - PURPOSE: To evaluate causative factors of cerebral edema after stereotactic
      radiosurgery or stereotactic radiation therapy in intracranial meningiomas.
      MATERIALS AND METHODS: Of 43 adult patients with intracranial meningiomas, three
      received 13.5-18-Gy single-fraction stereotactic radiosurgery; one received 19.8
      Gy in three fractions, one received 42 Gy in six fractions, and 31 received 32-36
      Gy in six to eight fractions of stereotactic radiation therapy; and seven
      received 45-54-Gy external-beam radiation with 20-28 Gy in five to seven
      fractions as concomitant stereotactic boosts. Brain edema was estimated by
      calculating the edema index. RESULTS: After irradiation, all 11 patients with
      parasagittal and four patients with nonparasagittal tumors developed worsening
      cerebral edema that necessitated the administration of steroids (P < .001). The
      statistically significant factors for the development of edema were parasagittal
      location, presence of pretreatment edema, sagittal sinus occlusion, and the use
      of more than 6 Gy per fraction. Five patients with parasagittal tumors developed
      life-threatening panhemispheric edema, which was fatal in one. The causative
      factors of panhemispheric edema were a large tumor, single-fraction stereotactic
      radiosurgery, or use of more than 6 Gy per fraction. CONCLUSION: A smaller dose
      per fraction and aggressive use of steroids may help prevent life-threatening
      complications due to worsening edema.

PMID- 9240537
TI  - Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and
      chemotherapy.
AB  - PURPOSE: To determine the appropriate radiation therapy and chemotherapy for
      primary lymphoma of the nasal cavity to improve the local control and survival
      rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal
      lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation
      therapy and chemotherapy (intravenous infusion). Radiation doses to the involved
      area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause
      specific survival rates were 91% and 73%, respectively. The 5- and 10-year
      disease-free survival rates were 83% and 59%, respectively. Eight patients
      developed recurrent disease: six at the local site, one in the cervical nodes,
      and one in the small intestine. Five of the six patients with local recurrence
      received less than 50 Gy. Four of the six patients developed recurrent disease in
      the treated area; the other two patients developed marginal recurrences.
      Prognostic factors such as age, sex, maximum tumor size, and lactate
      dehydrogenase level were of limited value. CONCLUSION: The most common recurrence
      site was the local site. To improve the local control rate, the involved area
      should be treated with high-dose radiation therapy. The clinical results did not
      demonstrate the usefulness of combination chemotherapy for stage IE nasal
      lymphoma.

PMID- 9240538
TI  - Prostate cancer: relative effects of demographic, clinical, histologic, and MR
      imaging variables on the accuracy of staging.
AB  - PURPOSE: To determine the effects on the accuracy of staging prostate gland
      cancer of diagnostic prediction rules based on demographic, clinical, histologic,
      and magnetic resonance (MR) image variables. MATERIALS AND METHODS: A total of
      200 cases from four medical centers were evaluated by nine radiologists
      experienced in MR imaging. The accuracies of the four diagnostic variables (age,
      prostate specific antigen level, Gleason tumor grade, and MR imaging findings)
      were measured, both singly and combined in a particular sequence, by calculating
      the area index of the receiver operating characteristic curve. RESULTS: The
      accuracy of staging with single variables (age, 0.58; prostate specific antigen
      level, 0.74; Gleason grade 0.73, MR image findings, 0.74) increased as the
      variables were optimally merged. The first two variables combined to yield an
      accuracy of 0.74; the first three combined to yield an accuracy of 0.81; and all
      four variables resulted in an accuracy of 0.86. In a clinically important subset
      of 69 cases for which antigen level and Gleason grade together were inconclusive
      for the purposes of staging, the addition of MR imaging findings resulted in an
      increase in accuracy from 0.55 to 0.73. CONCLUSION: Optimal merging of diagnostic
      test results yields an improvement in the accuracy of prostate cancer staging.

PMID- 9240539
TI  - Peritoneal inclusion cysts and their relationship to the ovaries: evaluation with
      sonography.
AB  - PURPOSE: To evaluate with sonography the relationship of the ovary to the
      peritoneal inclusion cyst. MATERIALS AND METHODS: The medical records, sonograms,
      and sonographic reports of 15 premenopausal women with surgically proved
      peritoneal inclusion cysts were examined. Twelve of these cases were examined
      prospectively. In another prospectively evaluated case, the sonogram was
      interpreted as revealing a peritoneal inclusion cyst; however, hydrosalpinx was
      confirmed with surgery. Thirteen women with peritoneal inclusion cysts had
      undergone pelvic surgery before sonography. Additional examination with computed
      tomography was performed in three women and with magnetic resonance imaging in
      another. RESULTS: The ovary was detected on sonograms in 12 of 15 women with
      peritoneal inclusion cysts. In nine of the 12 women, the ovary was demonstrated
      to be inside the cyst. Ten of 12 ovaries appeared normal. Cyst diameter ranged
      from 7.5 to 17.4 cm (mean, 11.6 cm). Sonograms of two cysts demonstrated internal
      echoes. Septa were seen in 11 of the 15 cysts. Cysts were ovoid in six women and
      irregular in nine; they were defined by adjacent pelvic structures. CONCLUSION:
      In premenopausal women with a history of pelvic surgery, the appearance on
      sonograms of the ovary inside a large, ovoid or irregular, anechoic cyst is
      characteristic of a peritoneal inclusion cyst.

PMID- 9240540
TI  - Atypical ductal hyperplasia diagnosed at stereotactic breast biopsy: improved
      reliability with 14-gauge, directional, vacuum-assisted biopsy.
AB  - PURPOSE: To compare histologic findings of atypical ductal hyperplasia (ADH) at
      14-gauge, directional, vacuum-assisted breast biopsy (hereafter, vacuum-assisted
      biopsy) and at 14-gauge, automated, large-core breast biopsy (hereafter, large
      core biopsy) with findings at histologic examination after surgical biopsy.
      MATERIALS AND METHODS: Nonpalpable breast lesions were diagnosed as ADH at
      histologic examination after vacuum-assisted biopsy in 88 lesions in seven
      institutions and after large-core biopsy in 55 previously reported lesions.
      Histologic findings at subsequent surgical biopsy were compared for the presence
      of carcinoma. RESULTS: On the basis of histologic findings of carcinoma at
      surgical biopsy, the diagnosis of ADH was not correct in 26 (48%) of 54 lesions
      sampled at large-core biopsy and in 13 (18%) of 74 lesions sampled at vacuum
      assisted biopsy (Fisher exact test, P < .0004). More tissue specimens were
      obtained at vacuum-assisted biopsy (mean, 15.8 specimens) than at large-core
      biopsy (mean, 9.7 specimens). Individual specimens were twice as large at vacuum
      assisted biopsy (mean, 34 mg) as at large-core biopsy (mean, 17 mg) (previously
      reported). CONCLUSION: ADH was diagnosed 2.7 times more reliably at vacuum
      assisted biopsy than at large-core biopsy (with no increase in complications)
      with most of the improvement as a result of acquisition of more than 10 specimens
      per lesion, but carcinoma was sufficiently underestimated with both methods to
      necessitate surgical biopsy.

PMID- 9240541
TI  - Comparison of the relative incidence of impalpable invasive breast carcinoma and
      ductal carcinoma in situ in cancers detected in patients older and younger than
      50 years of age.
AB  - PURPOSE: To compare the relative incidence of impalpable ductal carcinoma in situ
      (DCIS) and invasive breast carcinoma detected mammographically in women younger
      than 50 years of age and those aged 50 years and older. MATERIALS AND METHODS:
      Needle-wire localization and surgical biopsy were performed in 4,428 impalpable
      lesions in 3,734 patients. A total of 1,179 breast cancers were found. Histologic
      findings were reviewed retrospectively, and lesions were classified as invasive
      cancer or DCIS. The patients were categorized into two groups: those aged 50
      years and older and those younger than 50 years of age. RESULTS: A total of 294
      cancers were found in women younger than 50 years of age. Of these cancers, 137
      (46.6%) were DCIS and 157 (53.4%) were invasive. In women aged 50 years and
      older, 885 cancers were found. Of these, 325 (36.7%) DCIS and 558 (63.1%)
      invasive cancers were found. CONCLUSION: For mammographically detected breast
      carcinomas, there is a higher relative incidence (46.6% vs 36.6%) of DCIS in the
      younger age group, which may lend further support for aggressive screening of
      women younger than 50 years of age.

PMID- 9240542
TI  - Epidermal inclusion cysts of the breast: three lesions with calcifications.
AB  - PURPOSE: To determine whether there are any mammographic and ultrasonographic
      (US) features of epidermal inclusion cysts of the breast, including heterogeneous
      microcalcifications, that may be used to preclude unnecessary biopsy. MATERIALS
      AND METHODS: Clinical history and imaging findings in 15 patients who had
      undergone surgical excision of an epidermal inclusion cyst were reviewed.
      RESULTS: In 11 patients, imaging findings of an epidermal inclusion cyst were
      noted, including 10 patients with mammographic findings, one with US findings
      only, and seven with mammographic and US findings. The most common mammographic
      finding (in nine of 10 patients) was an isodense to high-density mass with a
      circumscribed margin; three circumscribed masses had multiple associated
      heterogeneous microcalcifications. In the seven patients with corresponding US
      findings, a circumscribed hypoechoic mass with through transmission was depicted.
      An additional US feature in six patients was extension of the mass into the
      dermis. CONCLUSION: Biopsy may be deemed unnecessary if the characteristic US and
      physical examination findings are present, even in the case of a cyst with
      heterogeneous microcalcifications.

PMID- 9240543
TI  - Pulmonary Langerhans cell histiocytosis: evolution of lesions on CT scans.
AB  - PURPOSE: To document the evolution of pulmonary lesions of Langerhans cell
      histiocytosis (LCH) with sequential computed tomography (CT). MATERIALS AND
      METHODS: Initial and final CT scans of 21 patients with LCH and CT evidence of
      pulmonary disease were compared retrospectively. Histologic confirmation of
      pulmonary involvement was available in 11 patients. RESULTS: On initial CT
      images, a nodular pattern (n = 14) was seen more frequently than a cystic pattern
      (n = 7). On final CT images, a cystic pattern (n = 14) was seen more often than a
      nodular one (n = 6). There was complete resolution of parenchymal abnormality in
      one case. Nodular opacities, thick-walled cysts, and ground-glass opacities
      underwent regression. Thin-walled cysts, linear opacities, and emphysematous
      lesions remained unchanged or progressed. CONCLUSION: Pulmonary CT allows good
      assessment of the evolution of LCH lesions. Nodular lesions probably represent
      active disease and often undergo regression or transform into cysts.

PMID- 9240544
TI  - US-guided thoracentesis: requirement for postprocedure chest radiography in
      patients who receive mechanical ventilation versus patients who breathe
      spontaneously.
AB  - PURPOSE: To identify a population of patients who may not need chest radiography
      after diagnostic thoracentesis by assessing and comparing the pneumothorax rates
      in patients with mechanical ventilation (intubation) versus spontaneously
      breathing patients (no intubation). MATERIALS AND METHODS: A retrospective review
      of all radiographs, clinical records, and ultrasound (US) scans obtained in 434
      patients who underwent US-guided thoracentesis was performed. Three hundred forty
      two patients were not intubated and 92 were intubated. Nine patients were
      excluded because of preexisting pneumothorax. The size of the effusion, the
      needle size used, and whether a pneumothorax occurred after the procedure were
      determined. RESULTS: Results demonstrated that only 10 pneumothoraces occurred
      (six in intubated and four in nonintubated patients). None of the nonintubated
      patients with pneumothorax and two of the six intubated patients with
      pneumothorax needed chest tubes. The difference in the pneumothorax rate between
      intubated and nonintubated patients was statistically significant (P < .01).
      CONCLUSION: Spontaneously breathing patients who undergo diagnostic thoracentesis
      do not need postprocedure chest radiography.

PMID- 9240545
TI  - Differentiation of simple and strangulated small-bowel obstructions: usefulness
      of known CT criteria.
AB  - PURPOSE: To evaluate the usefulness of known computed tomographic (CT) criteria
      for the differentiation of simple and strangulated small-bowel obstructions.
      MATERIALS AND METHODS: CT scans of 84 patients with simple (n = 43) and
      strangulated (n = 41) small-bowel obstructions caused by adhesions, hernia, and
      volvulus were reviewed retrospectively. Diagnoses were made with surgery (n = 55)
      and during clinical follow-up (n = 29). CT criteria evaluated were configuration
      of obstructed bowel loop, target sign, bowel wall thickening and enhancement,
      changes in mesentery and mesenteric vasculature, and amount and attenuation of
      ascites. RESULTS: CT findings that enabled the detection of strangulated
      obstructions were poor or no enhancement of bowel wall (sensitivity, 34%;
      specificity, 100%) and a serrated beak (sensitivity, 32%; specificity, 100%).
      When these two findings were excluded from analysis, a large amount of ascites,
      an unusual course of mesenteric vasculature, and diffuse engorgement of
      mesenteric vasculature were shown to be useful CT findings for performing
      multivariate regression analysis. Application of these five CT findings enabled
      identification of 35 (85%) of 41 patients with strangulated obstructions.
      CONCLUSION: Detecting a combination of selected, known CT criteria increases the
      diagnostic accuracy of CT to enable differentiation of simple and strangulated
      small-bowel obstructions.

PMID- 9240547
TI  - Staging of esophageal carcinoma in vitro with 4.7-T MR imaging.
AB  - PURPOSE: To determine the accuracy of 4.7-T magnetic resonance (MR) imaging for
      evaluating the mural invasion of esophageal carcinoma. MATERIALS AND METHODS:
      Sixty-seven esophageal specimens containing 70 squamous cell carcinomas were
      studied with a 4.7-T MR system with a 4-cm-diameter surface coil. Spin-echo MR
      images were obtained with a field of view of 4-6 cm, matrix size of 256 x 256,
      and section thickness of 3 mm, which resulted in a voxel size of 0.08-0.16 mm3.
      MR findings were compared with histopathologic findings, which served as the
      standard of reference. Tumor invasion on MR images was determined by consensus of
      two radiologists. RESULTS: T2-weighted images depicted six to eight layers of the
      normal esophageal wall; these correlated well with layers identified with
      histologic examination. In 66 (94%) of 70 cases of esophageal carcinoma, the
      depth of mural invasion visualized with MR imaging correlated well with that
      determined with histopathologic examination. The stage determined with MR
      imaging, however, was higher in two (3%) and lower in two (3%) cases than that
      determined with histopathologic examination. MR imaging enabled visualization of
      the gross features of tumor growth pattern, tumor ulceration, and adjacent lymph
      node involvement. CONCLUSION: MR imaging in vitro allows accurate assessment of
      the mural invasion of esophageal carcinoma and thus potentially enables
      preoperative histopathologic staging.

PMID- 9240548
TI  - Malignant esophageal fistulas and perforations: management with plastic-covered
      metallic endoprostheses.
AB  - PURPOSE: To evaluate prospectively the efficacy of plastic-covered metallic
      endoprostheses in patients with malignant esophageal fistulas and perforations.
      MATERIALS AND METHODS: Thirty-nine patients with incurable esophageal carcinoma
      who developed esophagorespiratory fistulas (n = 20) or perforations (n = 19) were
      treated with plastic-covered metallic stents. RESULTS: Covered Wallstent
      endoprostheses were placed in 36 patients and covered Gianturco stents in three.
      All 19 perforations and 18 of 20 fistulas were successfully closed (clinical
      success rate, 95%). Symptoms of aspiration or dysphagia improved in all
      successfully treated patients. Mean survival was 81.8 days (range, 1-370 days).
      One patient with a closed perforation developed a fistula 16 weeks later and was
      treated with a second, overlapping stent; three patients with recurrent fistulas
      were treated with additional esophageal stents (one patient) or tracheal stents
      (two patients). In four patients, stent migration (two Gianturco and two
      Wallstent endoprostheses) necessitated placement of an additional stent.
      CONCLUSION: Covered metallic stents offer effective treatment for perforations
      and fistulas in patients with esophageal malignancy. Patients with recurrent
      fistulas can be treated with additional stents. Fistulas close to the upper
      esophageal sphincter may be closed with placement of parallel covered metallic
      stents in the esophagus and trachea.

PMID- 9240546
TI  - Peritoneal tumor: MR imaging with dilute oral barium and intravenous gadolinium
      containing contrast agents compared with unenhanced MR imaging and CT.
AB  - PURPOSE: To compare fat-suppressed, gadolinium-enhanced, breath-hold magnetic
      resonance (MR) imaging after administration of dilute oral barium solution with
      unenhanced MR imaging and computed tomography (CT) in the detection of peritoneal
      tumors. MATERIALS AND METHODS: In 24 patients in whom peritoneal tumor was known
      or suspected, double-contrast MR imaging and CT were performed prospectively. MR
      imaging included T1-weighted, fast spin-echo T2-weighted, and immediate and
      delayed gadolinium-enhanced, breath-hold, fast multiplanar sequences with fat
      saturation. Helical and conventional dynamic CT were performed with intravenously
      and orally administered contrast media. MR images and CT scans were reviewed
      independently and prospectively by different pairs of radiologists for presence
      of peritoneal tumor in 17 anatomic sites. Imaging findings were compared with
      surgical and histopathologic results. RESULTS: Of the 24 patients, 18 had
      peritoneal tumor confirmed at surgery. Detection of tumor sites was superior with
      double-contrast MR images (mean sensitivity, specificity, and accuracy, 84%, 87%,
      and 86%, respectively) compared with CT scans (mean sensitivity, specificity, and
      accuracy, 54%, 91%, and 74%, respectively). Double-contrast MR imaging enabled
      better detection of carcinomatosis and tumors less than 1 cm in diameter (75%
      80%) than CT (22%-33%; P < .0001). CONCLUSION: Double-contrast MR imaging
      demonstrated more peritoneal tumors than CT or unenhanced spin-echo MR imaging.

PMID- 9240549
TI  - Rectal cancer: evaluation of staging with endosonography.
AB  - PURPOSE: To investigate whether endosonography is reliable in making radiation
      therapy decisions in rectal cancer, with possible downstaging taken into
      consideration. MATERIALS AND METHODS: Ninety patients (52 men, 38 women; median
      age, 69 years) with rectal adenocarcinoma underwent endosonography within 2 weeks
      before surgery and radiation therapy (performed in 54 patients). The tumor
      invasive edge was used for radiation therapy decision making. RESULTS: The local
      stage was accurately assessed in 65 patients (39 with and 26 without
      irradiation). The tumor invasive edge was accurately assessed in 63 patients.
      Overstaging was present in 19 patients; the tumor had grown almost through the
      muscularis propria in six. The invasive edge (P = .1) and lymph node status were
      overstaged more often in the patients with than in the patients without
      irradiation. Tumor was understaged in eight patients: The invasive edge did not
      penetrate but there was budding beyond the muscularis propria in five; the
      invasive edge penetrated the muscularis propria in two. In seven of the eight
      patients, growth beyond the muscularis propria was smaller than the
      endosonographic resolution. Three patients with understaged, nonirradiated tumors
      developed pelvic recurrence. None of the patients with irradiation and none of
      the 16 patients without irradiation but with correct assessment developed pelvic
      recurrence. CONCLUSION: Preoperative irradiation decision making on the basis of
      endosonographic findings is uncertain. Downstaging after preoperative irradiation
      must be considered.

PMID- 9240550
TI  - Peripheral cholangiocarcinoma of the liver: two-phase spiral CT findings.
AB  - PURPOSE: To determine characteristic features of peripheral cholangiocarcinoma on
      two-phase spiral computed tomographic (CT) scans. MATERIALS AND METHODS: Thirty
      four patients with peripheral cholangiocarcinoma underwent two-phase spiral CT.
      Hepatic arterial phase and portal venous phase images were obtained 30 and 65
      seconds, respectively, after the start of contrast material infusion. RESULTS:
      Thin, mild, incomplete rimlike contrast enhancement at the tumor periphery was
      seen on CT scans from both phases in 23 patients. Thick, continuous rimlike
      contrast enhancement and marked homogeneous contrast enhancement were present on
      scans in four patients and one patient, respectively. No definite contrast
      enhancement pattern was seen on scans in six patients. Other findings included
      increased lobar or segmental hepatic attenuation in adjacent normal liver during
      the arterial phase (n = 10), markedly low attenuation with amorphous areas of
      slightly high attenuation in the tumor during both phases (n = 33), internal
      septumlike linear structures (n = 8), narrowing or obstruction of the portal vein
      as it traversed the tumor (n = 16), and a patent hepatic vein (n = 4).
      CONCLUSION: Thin, mild, incomplete rimlike contrast enhancement at the tumor
      periphery and markedly low intratumoral attenuation with amorphous areas of
      slightly high attenuation during both scanning phases are typical findings of
      peripheral cholangiocarcinoma.

PMID- 9240551
TI  - Hepatic veno-occlusive disease after myeloablative treatment and bone marrow
      transplantation: value of gray-scale and Doppler US in 100 patients.
AB  - PURPOSE: To determine the value of gray-scale ultrasonography (US) and Doppler US
      in the prediction, diagnosis, and prognostic assessment of hepatic veno-occlusive
      disease (HVOD). MATERIALS AND METHODS: One hundred patients (median age, 22
      years; range, 18 months to 59 years) receiving total body irradiation or busulfan
      therapy as intensive treatment before hematopoietic stem cell transplantation
      were studied prospectively. Each patient underwent gray-scale and Doppler US
      examination before transplantation and weekly thereafter while hospitalized
      (about four examinations per patient). Seven gray-scale morphologic criteria and
      seven Doppler criteria were studied, yielding three individual scores: gray-scale
      score, Doppler score, and total score. RESULTS: Twenty-five patients developed
      HVOD; nine of these patients died. Positive predictive values of the 14 criteria
      were 31%-95%, and negative predictive values were 85%-96%. The three scores
      correlated with the clinical diagnosis of HVOD. Depending on the cutoff value,
      the positive predictive value of the total score was 44%-89% and the negative
      predictive value was 91%-98%. The gray-scale and Doppler criteria differed
      significantly between patients with HVOD and those with graft-versus-host disease
      of the liver (P = 10(-4)). CONCLUSION: Even if there is overlap in findings
      between patients with and those without HVOD, gray-scale and Doppler US are valid
      for positive and differential diagnosis and have predictive and prognostic
      relevance.

PMID- 9240553
TI  - Extremity veins: evaluation with fast-spin-echo MR venography.
AB  - The authors evaluated a flow-independent magnetic resonance (MR) imaging
      technique in extremity veins with slow flow that relies on the prolonged T2 of
      blood to create angiographic contrast. A commercially available heavily T2
      weighted fast-spin-echo sequence was optimized for MR venography in volunteer and
      phantom studies. Good depiction of venous anatomy was routinely obtained with the
      optimized method. Fast-spin-echo MR venography allowed evaluation of slow-flow
      systems such as the calf and forearm veins.

PMID- 9240552
TI  - Patient dose due to colon examination: dose assessment and results from a survey
      in The Netherlands.
AB  - PURPOSE: To determine the effective dose to the patient during radiographic colon
      examination. MATERIALS AND METHODS: The integral dose-area product was measured
      during colon examination in 1,733 patients aged 18-94 years. The effective dose
      was estimated from the dose-area product through computer simulations of
      radiation transport in anthropomorphic phantoms. The relation between patient
      dose and imaging or radiographic technique was considered. Patient dose from a
      biphasic colon examination was compared to that from a double-contrast
      examination. RESULTS: The factors for converting dose-area product to effective
      dose were 0.29 mSv x Gy(-1) x cm(-2) and 0.27 mSv x Gy(-1) x cm(-2) for the
      biphasic and the double-contrast studies, respectively. The average dose-area
      product for the biphasic colon examination was 21 Gy x cm2, of which 13 Gy x cm2
      was attributed to the double-contrast views. The average dose-area product was 29
      Gy x cm2 (range, 18-53 Gy x cm2); the average effective dose was 4.7 mSv (range,
      2.7-8.4 mSv). CONCLUSION: Careful selection of the radiologic technique resulted
      in a surprisingly low dose during the biphasic colon examination. It is
      recommended that additional filtration of at least 0.1-mm copper be applied and
      that a screen-film combination with a speed class of at least 400 be used. Dose
      reduction when using digital techniques is often not realized in clinical
      practice.

PMID- 9240554
TI  - Coronary arteries: retrospective cardiac gating technique to reduce cardiac
      motion artifact at spiral CT.
AB  - Coronary artery calcification is a marker of atherosclerosis. Detection and
      quantification has previously been accomplished with electron-beam computed
      tomography (CT). Use of spiral CT for this application has been limited by
      cardiac motion. The authors evaluated a retrospective cardiac-gated
      postprocessing technique that necessitates no modification of scanner hardware or
      software. At spiral CT in 26 patients, motion artifact was reduced, coronary
      arteries were consistently visualized, and quantification of calcification could
      be performed in those patients with prominent deposits. Coronary artery
      calcification screening can therefore be offered in sites that have access to
      only spiral CT.

PMID- 9240555
TI  - Volumetric method for evaluating magnetization transfer ratio of tissue
      categories: application to areas of white matter signal hyperintensity in the
      elderly.
AB  - An objective technique for analyzing magnetization transfer ratio of segmented
      tissues was used to evaluate differences between normal-appearing white matter
      and areas of white matter signal hyperintensity on T2-weighted magnetic resonance
      images in 23 healthy elderly subjects (mean age, 75 years). Segmented brain
      images (cerebrospinal fluid, gray matter, white matter, areas of white matter
      signal hyperintensity) computed from T1- and T2-weighted images were combined
      with magnetization-transfer-ratio images to produce magnetization-transfer-ratio
      histograms for each tissue. There was a significant 8.1% reduction in mean
      magnetization transfer ratio for areas of white matter signal hyperintensity
      compared with normal-appearing white matter (P < .001). The magnetization
      transfer ratio for all tissue categories was significantly negatively correlated
      with age (all, P < .05). This method of measuring magnetization transfer ratio
      was objective, independent of regional variations, and as reproducible as the
      segmentation procedure.

PMID- 9240556
TI  - Stereotactic breast biopsy of clustered microcalcifications with a directional,
      vacuum-assisted device.
AB  - The success rate with the traditional 14-gauge, core-biopsy, multiple-pass
      technique was compared with that of a directional vacuum-assisted device in
      sampling calcification clusters in the breast. Of the 130 focal calcification
      clusters sampled with the multiple-pass technique, 12 clusters (9.2%) had no
      particles depicted on radiographs of the specimen. Specimens from all 106 (100%)
      clusters sampled with the directional, vacuum-assisted instrument contained
      calcifications at radiography. The directional, vacuum-assisted device improved
      the ability to percutaneously sample breast calcifications.

PMID- 9240557
TI  - Solid localization marker for MR imaging.
AB  - A solid, stable material that can be easily cut into unique, identifiable shapes
      was compared with other localization markers used in magnetic resonance imaging
      to determine relaxation characteristics and chemical shift. The solid marker and
      the conventional oil-based markers caused substantial chemical shift artifacts
      and so should never be used when high levels of spatial accuracy are necessary,
      such as in stereotaxy. Although it had the lowest T2 of all the substances
      tested, the solid marker was useful in identifying structures when different
      coils, sequences, and fields of view were used.

PMID- 9240558
TI  - Modified technique for fluid aspiration from the hip in patients with prosthetic
      hips.
AB  - A modified technique was used for diagnostic aspiration of fluid from the hip in
      185 patients who had previously undergone total hip arthroplasty. The aspiration
      needle was advanced past the lateral aspect of the shaft of the prosthesis and
      into the dependent portion of the joint. Fluid was successfully aspirated in 181
      of 185 patients; thus the dry-tap rate was 2.2% (four of 185 patients). The
      modified technique was simple, could be performed quickly, and was effective for
      sampling joint fluid in patients with hip prostheses.

PMID- 9240559
TI  - Clinical importance of small pulmonary nodules detected at CT.

PMID- 9240560
TI  - Role of the retinoic acid receptor beta (RARbeta) during mouse development.
AB  - Homozygous RAR beta mutants are growth-deficient, but are fertile and have a
      normal longevity. They display homeotic transformations and malformations of
      cervical vertebrae and a retrolenticular membrane. This latter abnormality arises
      from the persistence and hyperplasia of the primary vitreous body. In contrast,
      we found that abnormalities of cranial nerves IX and X which were previously
      proposed to be specific features of the RAR beta mutant phenotype (Luo et al.,
      Mech. Dev. 53: 61-71, 1995) occur with the same low penetrance in wildtype
      littermates. Although the RAR beta protein is expressed at high levels in the
      striatum and interdigital mesenchyme, the brain and limbs of RAR beta mutants
      appear morphologically normal. RAR alpha/RAR beta double mutants display numerous
      visceral abnormalities, most of which are incompatible with post-natal life. The
      majority of these abnormalities was previously detected in RAR alpha/RAR beta2
      mutants with the notable exceptions of agenesis of the stapedial (2nd aortic arch
      derived) artery, thymic and spleen agenesis and abnormal inferior vena cava. RAR
      beta/RAR gamma double mutants show major ocular defects including a shortening of
      the ventral retina and pre-natal retinal dysplasia, both of which represent the
      only abnormalities of the fetal vitamin-A deficiency (VAD) syndrome not
      previously detected in RAR beta2/RAR gamma compound mutants. In addition, RAR
      beta is apparently functionally redundant with either RAR alpha or RAR gamma for
      the formation of a small subset of craniofacial skeletal elements, as well as for
      eyelid development and digit separation. We also provide evidence that, at least
      in some instances, this phenomenon of functional redundancy between RARs may be
      an artifactual consequence of gene knock-out.

PMID- 9240561
TI  - Crescent, a novel chick gene encoding a Frizzled-like cysteine-rich domain, is
      expressed in anterior regions during early embryogenesis.
AB  - We describe the isolation of a novel chicken gene that we have termed crescent,
      based on the most distinctive stage of its highly dynamic expression pattern
      during early embryogenesis. Crescent encodes a protein that in its N-terminal
      half shows the characteristic invariant 9 cysteine residues of the cysteine-rich
      domain (CRD) found in the Frizzled family of proteins, in Smoothened and in
      Collagen XVIII. The CRD of several Frizzled proteins have recently been shown to
      bind to Wg. Unlike Frizzled proteins, crescent does not contain a transmembrane
      domain and thus can not function as a receptor. Crescent expression is first
      found at stage XII (E-G&K) in the center of the area pellucida. On primitive
      streak formation, expression is detected in the entire anterior half of the area
      pellucida in the hypoblast layer. At maximal streak extension, crescent
      transcripts are localized primarily to the germinal crescent, where the
      primordial germ cells reside. During head process and head fold stages, crescent
      labels the anteriormost endodermal cells which will give rise to prospective
      foregut. With the commencement of somitogenesis, crescent expression rapidly
      wanes.

PMID- 9240562
TI  - N-cadherin protein distribution in normal embryos and in embryos carrying
      mutations in the homeobox gene Hoxa-4.
AB  - N-cadherin is a calcium-dependent adhesion molecule with a potential role in a
      variety of morphogenetic events. Although a dynamic pattern of expression in the
      mouse embryo has been suggested by in situ hybridization analysis, to date there
      has been no report of N-cadherin protein expression. In this immunohistochemical
      study we surveyed N-cadherin protein expression in the mid-late gestation mouse
      embryo utilizing a recently characterized monoclonal antibody. We found N
      cadherin expression in a wide array of tissues, including the brain, the eye,
      various cranial ganglia, the spinal cord, spinal ganglia, somites, vertebral and
      limb cartilage and perichondria, the developing lung and kidney, the enteric
      nervous system, and germ cells. These results suggest that N-cadherin protein
      expression, as in the chick embryo, correlates with the segregation of cells and
      with organogenesis. As cadherins have been proposed as targets of vertebrate Hox
      genes, we also examined N-cadherin expression in two lines of Hoxa-4 mutant mice.
      We did not observe any alterations in N-cadherin expression in either Hoxa-4 null
      embryos or in transgenic embryos that overexpress Hoxa-4 in the mesenchyme of the
      gut. However, the partial overlap in expression between Hox genes and N-cadherin,
      and the likelihood of redundancy in the regulation of target genes, leaves open
      the possibility that cadherins are direct or indirect targets of Hox genes during
      mouse embryogenesis.

PMID- 9240563
TI  - p34(cdc2) and mitotic cyclin expression in the developing quail neuroretina.
AB  - After an initial proliferation phase, neurons of the central nervous system (CNS)
      of higher eukaryotes remain postmitotic during their entire lifespan. This
      requires that a very stringent control be exerted on the cell division apparatus,
      whose molecular mechanisms remain quite elusive. Here we have used quail
      neuroretina as a model to study the control of cell division in the developing
      CNS. In vertebrates, embryonic neuroretinal cells (NR cells) stop their
      proliferation at different times depending on the cell type. Most NR cells in the
      quail embryo become postmitotic between E7 and E8. To acquire a better
      understanding of the molecular events leading to quiescence in NR cells, we have
      analyzed the expression of cdc2 and of two activators of p34(cdc2): cyclin A and
      cyclin B2 in the developing neuroretina. We report that these three proteins are
      downregulated between E7 and E9, suggesting that a common mechanism could block
      their transcription in differentiating neurons. We also report, using an
      immunohistochemical approach, that p34(cdc2) downregulation is correlated with
      the appearance of the microtubule-associated protein tau. These results strongly
      suggest that inhibition of cdc2 gene expression is closely linked to the
      achievement of terminal differentiation in neurons. However, we also show that
      postmitotic ganglion cells precursors begin to synthesize the early neuronal
      differentiation marker beta3-tubulin while p34(cdc2) is still detectable in these
      cells, suggesting that p34(cdc2) or a closely related kinase could play a role in
      some "young" postmitotic neurons.

PMID- 9240564
TI  - Immunocytochemical detection of acetylated alpha-tubulin and Drosophila synapsin
      in the embryonic crustacean nervous system.
AB  - The caridean shrimp Palaemonetes argentinus Nobili is well suited for studying
      developmental aspects of the crustacean nervous system due to its rapid embryonic
      development and short reproductive cycle. In the present paper, we demonstrate
      the pattern of central axonal pathways in embryos of this species by
      immunohistochemical detection of acetylated alpha-tubulin. Development of the
      neuropil was elucidated by using an antibody to a Drosophila synapsin. In the
      ventral nerve cord, the segmental axonal scaffold consists of the paired lateral
      connectives, a median connective, and the anterior and posterior commissures.
      Three nerve roots were found to branch off each ganglion anlage, i.e. the main
      segmental nerve root, a smaller posterior nerve and the intersegmental nerve.
      However, this pattern is different in the mandibular segment where no
      intersegmental nerve and only one commissure was encountered. The anterior part
      of the brain consists of a tritocerebral and a deutocerebral anlage as well asthe
      anlage of the medial protocerebrum. The latter is connected to the eyestalk via
      the protocerebral tract. The sequence of development of the eyestalk ganglia was
      demonstrated in specimens which were stained with the anti-synapsin antibody. The
      medulla terminalis and medulla interna are the first neuropils to appear and are
      still fused in early stages. Later, the medulla interna splits off the medulla
      terminalis. The lamina ganglionaris is the last of the eyestalk neuropils to
      develop. These findings prove that immunocytochemistry against acetylated alpha
      tubulin and synapsin are valuable tools for studying the development of the
      crustacean nervous system.

PMID- 9240565
TI  - Myogenesis in cultures of uniparental mouse embryonic stem cells: differing
      patterns of expression of myogenic regulatory factors.
AB  - The expression of myogenic regulatory factors (MRFs) in cultures of androgenetic
      (AG) and parthenogenetic (PG) embryonic stem (ES) cells were analyzed to identify
      a role for imprinted genes in the myogenic program. The time course and levels of
      expression of myf5, myogenin, MyoD1 and myf6 were assessed by semi-quantitative
      RT-PCR. A more rapid induction of myogenin expression was seen in AG ES cell
      cultures compared to control D3 ES cells, and myf6 was expressed by AG but not D3
      cells. Persistence of myf5 and MyoD1 expression at late stages of AG cell culture
      suggests that proliferation and differentiation are maintained. Myogenic
      differentiation was delayed in PG ES cells, but abundant levels of myogenin and
      myf6transcripts were subsequently observed. Absence of myf5 expression and only
      low MyoD1 expression at later stages of culture demonstrate a decline in
      proliferation in PG cultures. Igf2 was induced to high levels in the late phase
      of both AG and D3 but not PG cell cultures, indicating paternal allele-specific
      expression. Igf2 expression correlated with expression of MRF genes associated
      with myoblast proliferation rather than terminal differentiation. H19 was
      expressed at very low levels in both AG and PG ES cell cultures. The delay in
      myogenesis in PG cultures suggests that imprinted genes other than Igf2 and H19
      play a role at early stages of the myogenic program.

PMID- 9240566
TI  - Adult epidermal keratinocytes are endowed with pilosebaceous forming abilities.
AB  - Pluristratified epithelia of adult vertebrate skin continuously regenerate from
      stem cells, and the question still arises as to whether those cells are committed
      to the production of only one cell lineage, or in contrast they conserve their
      embryonic pluripotentiality. In order to investigate the abilities of adult
      cultured as well as wound healing epidermis, heterospecific fibroblast
      keratinocyte recombinations were performed, which allow unquestionable
      identification of the cells implicated in the structures that differentiate.
      Adult human cultured breast epidermal cells and full-thickness wound healing from
      human facial skin and foreskin were associated with either rabbit embryonic
      trichogenic dermis or cultured dermal papilla cells of adult rat, before grafting
      onto nude mice for two weeks to one month. In situ hybridization with a human
      specific sequence Alu probe labeled the human cells, whereas implanted rabbit or
      rat and host mouse cells were distinguished by the Hoechst staining of their
      nuclei. The results show that human adult cultured breast epidermal cells are
      able to form hair buds and to participate in hair follicle formation, while adult
      healing epidermis from a sparsely hairy skin as the human face or the dorsal skin
      of nude mouse, or even from a glabrous epidermis as the human foreskin, are able
      to differentiate pilosebaceous units. Although a follicular origin of the
      involved keratinocytes cannot be excluded in the three first cases, the formation
      of hair and sebaceous glands by foreskin keratinocytes of children 2 to 10 years
      old establishes the cutaneous appendage ability of the interfollicular epidermal
      stem cells. The formation of interspecies mosaic follicles also highlights the
      fact that there must be a significant level of commonality in the interactive
      signaling molecules used by epithelial cells from different species.

PMID- 9240567
TI  - Cytoplasmic transport in Drosophila ovarian follicles: the migration of
      microinjected fluorescent probes through intercellular bridges depends neither on
      electrical charge nor on external osmolarity.
AB  - Using video-intensified fluorescence microscopy and a pseudocolor display of
      fluorescence intensity, we analyzed the distribution of microinjected molecules
      within the nurse-cell/oocyte syncytium of Drosophila ovarian follicles. We varied
      the composition and the osmolarity of the culture solution as well as the
      electrical charge and the molecular mass of the microinjected fluorescent probe.
      As culture solutions, we used four simple salines (IMADS) and a complex tissue
      culture medium (R-14) that matched the osmolarity of adult hemolymph. Small
      amounts of two anionic dyes (Lucifer Yellow CH and Lucifer Yellow dextran) as
      well as of two cationic dyes (rhodamine 6G and tetramethylrhodamine dextran
      lysine) were iontophoretically microinjected either into a nurse cell or into the
      oocyte of stage-10 follicles. In the tissue-culture medium, within a few seconds
      following microinjection, all tested dyes passed through the intercellular
      bridges in both the anterior direction (to the nurse cells) and the posterior
      direction (to the oocyte), independent of their electrical charge or molecular
      mass. In all simple salines, irrespective of their osmolarity, Lucifer Yellow CH
      was found to preferentially migrate in the posterior direction and to accumulate
      in the oocyte due to progressive binding to yolk spheres. Thus, with this
      sensitive method, no correlation was detectable between the external osmolarity,
      the electrical charge and the preferential direction of migration of a
      microinjected probe. Our results indicate that the electrical gradient described
      by other authors does not exert significant influence on the migration of charged
      molecules through intercellular bridges in situ.

PMID- 9240568
TI  - Differential expression of microtubule associated protein MAP-2 in developing
      cochleovestibular neurons and its modulation by neurotrophin-3.
AB  - Microtubule associated proteins (MAPs) are essential cytoskeletal proteins in
      developing neurons. The present study was undertaken to analyze the expression of
      MAP2 and its isoforms (a,b,c) during the embryonal and early post-hatching
      development of chicken cochleovestibular ganglion (CVG) neurons. Moreover, we
      have investigated MAP2 expression in primary cultures of CVG neurons, and whether
      it is regulated by neurotrophin-3 (NT3). The expression of MAP2 immunoreactivity
      (IR) was studied using both Western blot and immunohistochemistry on tissue
      sections and primary cultures. In vivo MAP2c was expressed from incubation day 4
      (E4) to E10, and MAP2b was found in all embryonal stages studied and at post
      hatching day 10 (P10), whereas MAP2a was restricted to the post-hatching periods.
      The cellular localization of IR was in the neuronal perikarya and their
      peripheral processes (dendrites) but not in axons. Primary cultures matched the
      in vivo pattern of MAP2 expression, and IR was localized in neuronal cell bodies
      and the initial segment of the neuronal processes. Exogenous NT3 regulated the
      expression of MAP2 isoforms in a dose dependent manner. At the survival dose of
      0.5 ng/ml NT3, the main MAP2 expression was MAP2c. Conversely, at the
      neuritogenic dose of 5 ng/ml NT3 increased MAP2b and MAP2a expression, but not
      MAP2c. The present results demonstrate that MAP2 isoforms are developmentally
      regulated, thus suggesting that each isoform is specifically involved in CVG
      neuron maturation. Furthermore, we provide evidence of MAP2 regulation in culture
      by the neurotrophic factor NT3.

PMID- 9240569
TI  - The community effect in Xenopus myogenesis is promoted by dorsalizing factors.
AB  - The community effect describes a process required for Xenopus muscle progenitor
      cells to progress to the expression of myogenic genes. Past work has suggested
      that this effect is dependent on secreted factors released by dorsolateral or
      dorsal lip cells. We show here that known dorsalizing molecules as well as other
      natural dorsal lip factors contribute to, but do not wholly account for, the
      community effect. We conclude that, in addition to dorsalizing molecules, the
      community effect requires factors or conditions peculiar to the dorsolateral
      mesoderm, a region of the embryo that contains muscle progenitor cells.

PMID- 9240570
TI  - The final determination of Xenopus ectoderm depends on intrinsic and external
      positional information.
AB  - Traditionally the whole animal cap (ventral plus dorsal ectoderm) of amphibian
      blastula and gastrula stages was considered as a homogeneous cell mass, because
      both the isolated dorsal and ventral ectoderm without induction differentiated
      into ciliated (atypical) epidermis. Recent results suggest a predisposition of
      the dorsal and ventral ectoderm. We used a special experimental approach, i.e.
      injection of activin as inducer into the blastocoel of intact Xenopus blastulae
      before the isolation of animal caps and fluorescein-dextran-amine (FDA) as a
      lineage tracer. In recombinants of FDA-labeled and unlabeled ectoderm we showed
      that the cells of the dorsal ectoderm mainly differentiate into neural tissue and
      notochord when they remain at their original dorsal position. In contrast, when
      small pieces of dorsal ectoderm are transplanted to the ventral part of animal
      caps, most of the descendants form epidermis. However, when small pieces of the
      ventral ectoderm are transplanted to the dorsal side, they significantly
      contribute to neural tissue and notochord. These results suggest that the
      prepattern in Xenopus animal caps of the late blastula and early gastrula stages
      is labile and reversible. Still more important is the fact that the fate of
      individual cells depends on the site of their localization within the animal cap.
      This means that cells in the dorsal most or ventral most part of the animal cap,
      respectively, will not randomly differentiate into all cell types, but
      predominantly into dorsal or ventral derivatives, respectively.

PMID- 9240571
TI  - Correlation between RA-induced apoptosis and patterning defects in regenerating
      fins and limbs.
AB  - We have compared the ability of RA to induce apoptosis in regenerating fins and
      limbs in order to establish whether there may be a possible causal relationship
      between RA-induced cell death and the different patterning abnormalities observed
      in these two systems following RA treatment. In regenerating fins RA affects the
      anteroposterior axis and induces narrowing of the fin and fusion of rays. In
      regenerating limbs however, it mainly affects the proximodistal axis, where dose
      dependent duplications of segments are observed. We report here that RA increases
      cell death by apoptosis both in fin and limb regenerates independently from the
      route of administration, but in distinct cell populations. In regenerating fins,
      RA-induced apoptosis is observed only in the wound epidermis, whereas in
      regenerating limbs significant apoptosis is observed mainly in the blastema
      mesenchyme. Altogether, these findings support the view that RA-induced apoptosis
      is causally related to the patterning defects observed in fins and limbs.

PMID- 9240572
TI  - Thyroid hormone receptors in perennibranchiate amphibians.
AB  - Thyroid hormone has long been known to induce metamorphosis in amphibians. The
      understanding of the molecular steps controlling the completion of metamorphosis
      has nevertheless been hampered by the complexity of this event. The comparison of
      organisms in which metamorphosis does or does not occur, may provide clues into
      the molecular cascade that control it. Up to now the available data suggest that
      perennibranchiate amphibians retain their larval characters mainly because their
      tissues do not respond to thyroid hormones. In such a context the recent
      identification of a thyroid hormone receptor alpha in the perennibranchiate
      Proteus anguinus is provocative (Ho Huynh et al., Int. J. Dev. Biol. 40:537-543,
      1996). In the present paper, we provide evidences that this recently described
      sequence is in fact a sequence from Xenopus laevis. Indeed, we identified the
      authentic thyroid hormone receptors of both alpha and beta types in two
      perennibranchiate species Necturus maculosus and Proteus anguinus. The various
      controls required to ascertain the authenticity of a developmental gene cloned by
      PCR or RT-PCR analysis are presented. The results reported in the present paper
      are relevant with phylogenetical analysis. This induces our team to conclude that
      the Proteus TR alpha sequence reported by Ho Huynh et al. (1996) reflects a
      contamination of the RT-PCR by Xenopus laevis material.

PMID- 9240573
TI  - Incorporation of cultured embryonic cells into transgenic and chimeric, porcine
      fetuses.
AB  - The derivation of murine, embryonic stem cells, and their use in the generation
      of transgenic mice, are well-established procedures. Application of these
      methodologies to non-murine species, however, remains to be fully realized. Non
      murine embryonic stem cells would be of considerable value to studies in
      comparative development, and would raise important implications for agriculture
      and biotechnology. Here we report the achievement of chimerism and transgenesis
      in the domestic pig (Sus scrofa) at a fetal stage by the embryonic stem-cell
      methodology, using an embryonic cell line which previously we described as having
      the capacity to differentiate in vitro. This entailed: transformation, by
      electroporation, of a cell line, PE1, with the bacterial gene for neomycin
      resistance; re-introduction of a polyclonal population of neo-PE1 cells into host
      blastocysts, followed by transfer of reconstructed embryos into a pseudopregnant
      recipient; and subsequent derivation of transgenic and chimeric porcine fetuses,
      as determined by two independent molecular assays of fetal genomic DNA. In the
      first instance, chimerism was revealed in one fetus by the presence of the
      transgene, as detected by Southern blotting; and in the second instance, in that
      and another fetus by the presence of supernumerary alleles for the class II major
      histocompatibility locus, SLA-DQB*C, by single-strand conformation polymorphic
      analysis. The contribution of neo-PE1 cells to the first chimeric and transgenic
      fetus was approximately 25%, and to the second chimeric fetus, below the level of
      detection by Southern blotting (i.e. less than 10%). The results indicate that,
      at the time of embryo reconstitution, a proportion of neo-PE1 cells were
      pluripotent and of the primary ectodermal lineage.

PMID- 9240574
TI  - Nonobstetric conditions causing hypoxia during pregnancy: asthma and epilepsy.
AB  - Nonobstetric medical emergencies of hypoxia may be difficult to recognize in
      pregnant patients whose normal physiologic condition is altered by the pregnant
      state. Keys to early recognition of hypoxia in pregnancy may result in
      appropriate medical interventions for treatment of asthma and seizures that
      minimize ill effects to mother and fetus. Preventive measures and patient
      education are important to reducing the incidence of emergencies such as status
      asthmaticus and status epilepticus.

PMID- 9240575
TI  - The preterm prediction study: patterns of cervicovaginal fetal fibronectin as
      predictors of spontaneous preterm delivery. National Institute of Child Health
      and Human Development Maternal-Fetal Medicine Units Network.
AB  - OBJECTIVE: Our purpose was to determine how various temporal patterns of fetal
      fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin
      test results and spontaneous preterm delivery. STUDY DESIGN: A total of 2929
      women had vaginal and cervical fetal fibronectin tests obtained at least once at
      24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four
      gestational ages. Fetal fibronectin values > or = 50 ng/ml were considered
      positive. Various patterns of positive and negative tests were evaluated for
      prediction of (1) whether the next fetal fibronectin test would be positive or
      negative and (2) the percent of women with a spontaneous preterm delivery > or =
      4 weeks after the last fetal fibronectin test at < 30, < 32, < 35, and < 37
      weeks' gestational age. RESULTS: Women with previous negative test results had
      only a 3% chance of a subsequent positive test result; however, if the last test
      result was positive, 29% of the next tests were positive. Of the 1870 women with
      tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one
      positive result, 1.8% had two positive results, and 0.8% had three or four
      positive results. The higher the percent of positive tests at 24 to 26 weeks, at
      28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent
      spontaneous preterm birth. As an example, the risk of spontaneous preterm birth
      at < 30 weeks for women with two negative fetal fibronectin test results at 24
      and 26 weeks was 0.3% versus 16% for women with two positive results. CONCLUSION:
      The presence of a positive cervical or vaginal fetal fibronectin test result
      predicts subsequent positive fetal fibronectin positivity and subsequent
      spontaneous preterm birth. The greater the percent of positive results, the
      higher is the risk of spontaneous preterm birth. After a positive test result,
      two negative results are required before the risk of spontaneous preterm birth
      returns to baseline.

PMID- 9240576
TI  - Fetal fibronectin as a predictor of preterm birth in patients with symptoms: a
      multicenter trial.
AB  - OBJECTIVE: Our aim was to determine whether the presence of fetal fibronectin in
      vaginal secretions of patients with symptoms suggestive of preterm labor predicts
      preterm delivery. STUDY DESIGN: Patients who were examined at the hospital
      between 24 weeks' and 34 weeks 6 days' gestation with intact membranes, no prior
      tocolysis, symptoms suggestive of preterm labor, and cervical dilation < 3 cm
      were recruited at 10 sites. Swabs of the posterior fornix were assayed for the
      presence of fetal fibronectin by monoclonal antibody assay, with a positive
      result defined as > or = 50 ng/ml. Results were not available to the managing
      physicians. Tocolysis was used when clinically indicated after specimen
      collection. RESULTS: A total of 763 patients had fetal fibronectin results and
      pregnancy outcome data available for analysis. Fetal fibronectin was detected in
      specimens from 150 (20%) patients. Compared with patients who had negative
      results, patients who had positive results for fetal fibronectin were more likely
      to be delivered within 7 days (relative risk 25.9 [95% confidence interval 7.8 to
      86]), within 14 days (relative risk 20.4 [95% confidence interval 8.0 to 53]),
      and before 37 completed weeks (relative risk 2.9 [95% confidence interval 2.2 to
      3.7]). The negative predictive values for delivery within 7 days, within 14 days,
      and at < 37 weeks were 99.5%, 99.2%, and 84.5%, respectively. When we used
      multiple logistic regression analysis to control for potential confounding
      variables among singleton pregnancies, only the presence of fetal fibronectin
      (odds ratio 48.8, 95% confidence interval 7.4 to 320), prior preterm birth (odds
      ratio 8.3, 95% confidence interval 1.5 to 46.6), and tocolysis (odds ratio 4.1,
      95% confidence interval 1.0 to 16.0) were associated with birth within 7 days;
      fetal fibronectin (odds ratio 3.6, 95% confidence interval 2.2 to 5.9), prior
      preterm birth (odds ratio 2.5, 95% confidence interval 1.4 to 4.4), cervical
      dilatation > 1 cm (odds ratio 2.9, 95% confidence interval 1.6 to 5.2), and
      tocolysis (odds ratio 4.5, 95% confidence interval 2.8 to 7.2) were all
      independently associated with delivery before 37 weeks. CONCLUSION: In a
      population of patients with symptoms, the presence of fetal fibronectin in
      vaginal secretions best defines a subgroup at increased risk for delivery within
      7 days; the high negative predictive value of fetal fibronectin sampling supports
      less intervention for patients with this result.

PMID- 9240577
TI  - Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and
      tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral
      palsy.
AB  - OBJECTIVE: Ultrasonographically detectable neonatal brain white matter lesions
      are the most important identifiable risk factor for cerebral palsy. Inflammatory
      cytokines released during the course of intrauterine infections have been
      implicated in the genesis of brain white matter lesions and subsequent cerebral
      palsy. This study was undertaken to determine whether fetuses who subsequently
      were diagnosed to have periventricular brain white matter lesions could be
      identified by determining the concentrations of inflammatory cytokines in the
      amniotic fluid. STUDY DESIGN: Women with complicated preterm gestations underwent
      amniocentesis for clinical indications. Amniotic fluid concentrations of tumor
      necrosis factor-alpha, interleukin-1beta, interleukin-6, and the natural
      interleukin-1 receptor antagonist were determined by immunoassay. Periventricular
      white matter lesions of the neonate were diagnosed by neurosonography. Univariate
      and multivariate analyses were conducted. RESULTS: Ninety-four women and their
      neonates were included in the study; white matter lesions were diagnosed in 24%
      (23/94) of the newborns. The mothers of newborns with brain white matter lesions
      had higher median concentrations of tumor necrosis factor-alpha, interleukin
      1beta, and interleukin-6 (but not interleukin-1 receptor antagonist) in amniotic
      fluid than did those who were delivered of newborns without white matter lesions
      (p < 0.01 for each). Acute histologic chorioaminionitis was more common in the
      placentas of neonate with white matter lesions than in those without these
      lesions (82% [18/22] vs 42% [30/71], p < 0.005). Neonates with white matter
      lesions were delivered at a lower mean gestational age and birth weight and had a
      higher rate of significant complications (including respiratory distress
      syndrome, intraventricular hemorrhage, and infection-related complications) than
      did those without white matter lesions. The differences in median interleukin
      1beta and interleukin-6 levels between these two groups remained significant
      after adjustment for gestational age and birth weight (interleukin-6: odds ratio
      5.7, 95% confidence interval 1.3 to 24.4; interleukin-1beta: odds ratio 4.4, 95%
      confidence interval 1.1 to 17.0). Of the 94 newborns included in this study, 11
      died before age 6 months and eight had cerebral palsy; all eight had white matter
      lesions and elevated cytokine levels in amniotic fluid. Histologic
      chorioamnionitis was more common in the placentas of neonates with cerebral palsy
      than in those without cerebral palsy (86% [6/7] vs 44% [33/75], p < 0.05).
      CONCLUSIONS: Infants at risk for development of brain white matter lesions can be
      identified by the concentrations of interleukin-6 and interleukin-1beta in
      amniotic fluid. Our findings support the hypothesis that inflammatory cytokines
      released during the course of intrauterine infection play a role in the genesis
      of brain white matter lesions.

PMID- 9240578
TI  - Correlation of neonatal nucleated red blood cell counts in preterm infants with
      histologic chorioamnionitis.
AB  - OBJECTIVE: The aim of this study was to compare the neonatal nucleated red blood
      cell counts in preterm infants in the presence and absence of clinical and
      histologic chorioamnionitis while controlling for gestational age and birth
      weight percentile. STUDY DESIGN: Nucleated red blood cell counts were obtained
      from preterm infants delivered after preterm labor or preterm premature rupture
      of membranes. Patients were divided on the basis of clinical and histologic
      chorioamnionitis. Nucleated red blood cell counts between groups were compared,
      and regression analysis controlling for gestational age and birth weight
      percentile was performed. RESULTS: Of 359 patients, both measures of infection
      status were significantly associated with increased nucleated red blood cell
      counts. In the regression analysis histologic chorioamnionitis retained
      significance, whereas clinical chorioamnionitis did not. CONCLUSIONS: Histologic
      chorioamnionitis produces an erythropoietic response in the fetus. Whether fetal
      erythropoiesis is a direct response to mediators of inflammation or whether it is
      the result of a rise in erythropoietin is unknown.

PMID- 9240579
TI  - Vitamin A and birth defects.
AB  - OBJECTIVE: Our objective was to determine whether moderate doses of vitamin A are
      teratogenic. STUDY DESIGN: This was a geographically based case-control study.
      Women whose pregnancies produced offspring with neural tube defects (n = 548) or
      major malformations other than neural tube defects (n = 387) and normal control
      subjects (n = 573) were interviewed to determine periconceptional vitamin A
      supplement exposure levels. RESULTS: The proportion of women consuming doses of
      vitamin A between 8000 and 25,000 IU was no greater in the major malformations
      group or the group with neural tube defects than in the normal control group. For
      exposure from supplements and fortified cereals combined, women consuming >8000
      and >10,000 IU daily had odds ratios for major malformations of 0.79 (95%
      confidence interval 0.40 to 1.53) and 0.73 (95% confidence interval 0.27 to
      1.96), respectively, compared with women consuming <5000 IU. The results for
      neural tube defects were similar. For cranial neural crest defects the odds
      ratios were 0.76 (0.22 to 2.56) and 1.09 (0.24 to 4.98) for exposure to >8000 and
      >10,000 IU, respectively, versus exposure to <5000 IU. CONCLUSIONS: This study
      found no association between periconceptional vitamin A exposure at doses >8000
      IU or >10,000 IU per day and malformations in general, cranial neural crest
      defects, or neural tube defects. If vitamin A is a teratogen, the minimum
      teratogenic dose appears to be well above the level consumed by most women during
      organogenesis.

PMID- 9240580
TI  - Incidence of persistent birth injury in macrosomic infants: association with mode
      of delivery.
AB  - OBJECTIVE: Our purpose was to determine the incidence of birth injury in a cohort
      of macrosomic infants (birth weight >4000 gm) and analyze the association between
      persistent injury and delivery method. STUDY DESIGN: Deliveries of 2924
      macrosomic infants were reviewed. Outcomes were compared with those of 16,711
      infants with birth weights between 3000 and 3999 gm. RESULTS: Macrosomic infants
      had a sixfold increase in significant injury relative to controls (relative risk
      6.7,95% confidence interval 6.5 to 6.9). Risk of trauma correlated with delivery
      mode: forceps were associated with a fourfold risk of clinically persistent
      findings compared with spontaneous vaginal delivery or cesarean section. However,
      the overall incidence of persistent cases remained low (0.3%); a policy of
      elective cesarean section for macrosomia would necessitate 148 to 258 cesarean
      sections to prevent a single persistent injury. Avoidance of operative vaginal
      delivery would require 50 to 99 cesarean sections per injury prevented.
      CONCLUSIONS: These findings support a trial of labor and judicious operative
      vaginal delivery for macrosomic infants.

PMID- 9240581
TI  - Paralysis of the preterm rabbit fetus inhibits the pulmonary uptake of
      intraamniotic iron dextran.
AB  - OBJECTIVE: Whether fetal breathing movements or gasping result in the movement of
      amniotic fluid substances into the distal airways remains controversial. We
      evaluated the effect of paralysis of the preterm rabbit fetus on the pulmonary
      distribution of iron dextran. STUDY DESIGN: Laparotomy was performed on 10 New
      Zealand White rabbits of 25 days' gestation (term 31 days) under general
      anesthesia. Fetuses in one uterine horn were given an intramuscular injection of
      pancuronium (1.5 mg/kg) and fetuses in the other horn were given an equal volume
      of normal saline solution as controls. A 1 ml volume of iron dextran (100 mg/ml)
      was injected into the amniotic sac of all fetuses. The laparotomy was closed, and
      20 to 24 hours later the fetuses were removed by hysterotomy and assessed for
      paralysis. Necropsy was performed. Lungs were stained with prussian blue and
      evaluated histologically for the presence of iron. RESULTS: A total of 92 pups
      were delivered (49 given pancuronium, 43 given normal saline solution), of which
      64 were born alive. There were no differences between groups for live births (31
      pancuronium, 33 normal saline solution), pup body weight, or lung weight. Pups
      given normal saline solution demonstrated more breathing motions, spontaneous
      movement, and brown (color of iron dextran) stomach contents than did the pups
      given pancuronium (p < 0.001). At necropsy a greater number of control pups
      (31/33) had brown lungs grossly compared with pups given pancuronium (2/31, p <
      0.001). Lung histologic examination showed that more control pups (29/29) had
      iron in the trachea and main bronchi compared with pancuronium pups (0/27, p <
      0.001), and more control pups (29/29) had iron in the distal lung airways
      compared with pancuronium pups (0/27, p < 0.001). With use of the Optimas Image
      Analysis System, iron in the lungs of control pups was found to be equally
      distributed between right versus left lungs, upper half versus lower half lungs,
      and anterior versus posterior lung sections. More iron was identified in the
      central airways than in the periphery (p < 0.001). CONCLUSION: We conclude that
      paralysis prevents the uptake of iron dextran into the main and distal airways of
      the rabbit fetus. Although lung fluid production results in a net efflux of
      fluid, we speculate that fetal breathing movements can result in the movement of
      fluid into distal airways and potentially provide fetal therapy.

PMID- 9240582
TI  - Amniotic fluid tumor necrosis factor-alpha and the risk of respiratory distress
      syndrome among preterm infants.
AB  - OBJECTIVE: We examined the effect of exposure to amniotic fluid infection and
      cytokines on the pulmonary outcome of preterm infants. STUDY DESIGN: A cohort of
      136 preterm infants born to women in preterm labor had amniotic fluid cultures
      and tumor necrosis factor-alpha assays performed. Amniotic fluid was collected by
      transabdominal amniocentesis. Outcome measures included respiratory distress
      syndrome and length of oxygen and ventilator support. Logistic regression and Cox
      proportional hazards regression adjusted for birth weight and other confounders.
      RESULTS: Respiratory distress syndrome developed in 67 (49%) of 136 infants.
      Elevated amniotic fluid tumor necrosis factor-alpha levels and amniotic fluid
      infection were significantly associated with respiratory distress syndrome. This
      association persisted after adjustment for birth weight. Infants exposed to tumor
      necrosis factor-alpha remained on supplemental oxygen and assisted ventilation
      longer and had longer hospital stays compared with nonexposed infants.
      CONCLUSION: Prenatal exposure to tumor necrosis factor-alpha may be a risk factor
      for respiratory distress syndrome and its complications.

PMID- 9240583
TI  - Placental apoptosis in normal human pregnancy.
AB  - OBJECTIVES: The study aims were to conclusively demonstrate apoptosis in the
      human placenta and to quantify its incidence at different stages of pregnancy.
      STUDY DESIGN: Placental samples were obtained from 28 first-trimester pregnancies
      and 38 uncomplicated third-trimester pregnancies. Light microscopy, electron
      microscopy, and terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate marker nick end-labeling staining were used to identify apoptosis.
      Light microscopy was used to quantify its incidence. RESULTS: Apoptosis has been
      conclusively demonstrated within placental tissue. Quantification of apoptosis
      (medians and interquartile ranges) was as follows: first trimester (n = 28),
      0.07% of cells (0.05% to 0.14%); third trimester (n = 39), 0.14% of cells (0.09%
      to 0.20%). The incidence of apoptosis was significantly higher in the third
      trimester than in the first trimester (p < 0.01, Mann-Whitney U test).
      CONCLUSIONS: Placental apoptosis increases significantly as pregnancy progresses,
      suggesting that it may play a role in the normal development and aging of the
      placenta.

PMID- 9240584
TI  - Electrocortical and heart rate response during vibroacoustic stimulation in fetal
      sheep.
AB  - OBJECTIVE: Our purpose was to study effects of vibroacoustic stimuli on
      electrocortical activity and heart rate changes in fetal sheep in utero. STUDY
      DESIGN: Seven chronically instrumented near-term fetal sheep were repeatedly
      stimulated by an electronic artificial larynx for 32 seconds during periods of
      rapid-eye-movement and non-rapid-eye-movement sleep. Responses to vibroacoustic
      stimulation were obtained by spectral analysis of the electrocorticogram (fast
      Fourier transform) and by assessment of changes in fetal heart rate and fetal
      heart rate variability. RESULTS: During non-rapid-eye-movement sleep
      vibroacoustic stimulation led to electrocorticogram desynchronization that
      consisted of a marked reduction of delta and theta band power (p < 0.05). A
      concomitant fetal heart rate decrease and fetal heart rate variability increase
      were also noted (p < 0.05). During rapid-eye-movement sleep vibroacoustic
      stimulation induced a significant increase in alpha and beta band power (p <
      0.05) and a slight deviation in basal fetal heart rate and fetal heart rate
      variability (p < 0.05). CONCLUSION: Vibroacoustic stimulation of fetal sheep
      provokes reproducible changes in fetal electrocortical activity and heart rate
      patterns. These changes, which are not easily identifiable in gross polygraphic
      assessments of the fetal behavioral state, are indicative of fetal arousal.

PMID- 9240585
TI  - The effects of oligohydramnios and cervical cord transection on lung growth in
      experimental pulmonary hypoplasia in rabbits.
AB  - OBJECTIVE: Our goal was to examine the effects of oligohydramnios and cervical
      cord transection on fetal lung development, pulmonary surfactant, and lung
      mechanics in rabbits. STUDY DESIGN: The amniotic fluid was shunted into the
      maternal abdominal cavity in a group of 12 fetal rabbits. In another group (n =
      12) high cervical cord transection was performed at day 24 of gestation. Another
      12 littermates not operated on served as the control group. Fetuses were
      delivered on day 30 of gestation by cesarean section and immediately put to
      death. The body weight and wet lung and liver weights were measured. To determine
      the extent of fetal lung growth, we measured the size of lung acini, the number
      of terminal airspaces, and the diameter of alveoli. We also measured the dynamic
      compliance of the lung, the concentration of phosphatidylcholine, and the
      lecithin/sphingomyelin ratio in lung lavage fluid at birth. RESULTS: Amniotic
      fluid shunting produced a significant reduction in amniotic fluid volume.
      Amniotic shunt and cervical cord transection significantly decreased wet lung
      weight and fetal lung/body weight ratio compared with the control. The
      concentration of phosphatidylcholine and the lecithin/sphingomyelin ratio in lung
      fluid lavage from fetuses with amniotic shunt were significantly higher than the
      values for control and cord transection fetuses. Histopathologic examination of
      the lungs showed significant reductions in the size of acini, the number of
      terminal airspaces, and the diameter of alveoli in shunted and cord transection
      groups compared with the control group. The dynamic compliance of transection
      fetuses was significantly reduced compared with control and shunted fetuses.
      CONCLUSION: Our results indicate that oligohydramnios or cervical cord
      transections cause pulmonary hypoplasia. However, oligohydramnios-induced
      pulmonary hypoplasia is associated with increased pulmonary surfactant compared
      with control and cord transection fetuses.

PMID- 9240586
TI  - Aspirin induces increased expression of both prostaglandin H synthase-1 and
      prostaglandin H synthase-2 in cultured human placental trophoblast.
AB  - OBJECTIVE: We tested the hypothesis that aspirin affects trophoblast like other
      epithelial cells do, by inhibiting prostanoid production, inducing prostaglandin
      H synthase-2 expression, and enhancing secretion of 15-hydroxyeicosatetraenoic
      acid. STUDY DESIGN: Cytotrophoblast from placentas (n = 15) of uncomplicated
      singleton pregnancies were cultured in medium 199 for 4 to 72 hours in the
      presence or absence of aspirin. RESULTS: Aspirin (10(-4) M) inhibited (p < 0.01)
      average trophoblast prostaglandin E2 release by 60% and thromboxane B2 by 86%.
      Western immunoblotting showed the prostaglandin H synthase-1 was constitutively
      expressed in cytotrophoblast, and aspirin treatment caused a twofold increase in
      prostaglandin H synthase-1 expression. Prostaglandin H synthase-2 was also
      constitutively expressed in untreated cytotrophoblast but at lower levels than
      prostaglandin H synthase-1. Aspirin enhanced prostaglandin H synthase-2
      expression in trophoblast cultures, but prostaglandin H synthase-2 contributed a
      range of only 10% to 33% (n = 4) of the total cellular prostaglandin H synthase
      protein pool even after aspirin induction. The increased prostaglandin H synthase
      expression depended on both transcription and translation because actinomycin D
      and cycloheximide each inhibited the increased prostaglandin H synthase protein
      expression after aspirin treatment. The aspirin induction of prostaglandin H
      synthase was accompanied by decreased release of 15-hydroxyeicosatetraenoic acid.
      CONCLUSIONS: Trophoblast differs from other cells studied because aspirin
      enhances expression of both prostaglandin H synthase-1 and prostaglandin H
      synthase-2 isozymes while decreasing, instead of increasing, the secretion of 15
      hydroxyeicosatetraenoic acid. The aspirin effects on prostaglandin H synthase
      synthesis and 15-hydroxyeicosatetraenoic acid release in trophoblast suggest that
      the mechanisms of action for aspirin in the prophylaxis of preeclampsia may be
      more diverse than simply altering platelet thromboxane production.

PMID- 9240587
TI  - Umbilical flow distribution to the liver and the ductus venosus: an in vitro
      investigation of the fluid dynamic mechanisms in the fetal sheep.
AB  - OBJECTIVES: The study aimed to determine whether an inherent difference in
      vascular resistance between the liver and the ductus venosus influences the
      distribution of umbilical blood to the two sections of the circulation. STUDY
      DESIGN: Flow was measured in vitro in six fetal sheep liver preparations,
      perfused at varying pressures with saline solution or with blood of hematocrit
      25% to 26% or 41% to 42%, with an occluded or open ductus venosus, at a
      temperature of 19 degrees C to 21 degrees C with likely absence of local control
      mechanisms. RESULTS: There was a linear relationship between pressure and flow
      through the liver, except at very low pressures when the linearity was broken. A
      closing pressure of 1 to 4 mm Hg was noted, lowest with saline solution and
      highest with hematocrit 42%. An open ductus venosus reduced overall resistance
      and brought down the closing pressure to <1 mm Hg. This also occurred during
      perfusion with high hematocrit. Thus at low pressures a proportionally greater
      fraction of umbilical flow was directed through the ductus venosus. CONCLUSIONS:
      The different physical properties of the portal vasculature and of the ductus
      venosus, pressure and viscosity, have a substantial impact on distribution of
      umbilical flow to the two parts of the circulation. Reduced umbilical venous
      pressure and increased hematocrit favor an increased fraction of flow through the
      ductus venosus.

PMID- 9240589
TI  - Nuchal cord type A and type B.
AB  - Nuchal cord type A and type B need to be distinguished at delivery. Type A
      encircles the neck in an unlocked pattern. Type B encircles the neck in a locked
      pattern. In a prospective review of nuchal cords the type B pattern occurred in 1
      in 50 births. Cesarean section and stillbirth were associated with type B nuchal
      cord.

PMID- 9240588
TI  - Central hemodynamic effects of oxytocin and interaction with magnesium and
      pregnancy in the isolated perfused rat heart.
AB  - OBJECTIVE: Our purpose was to determine the cardiac effects of oxytocin in the
      isolated perfused rat heart model and to see whether pregnancy or pharmacologic
      levels of magnesium modifies the hormone's action. STUDY DESIGN: Hearts were
      excised from 30 female Sprague-Dawley rats (15 pregnant, 15 nonpregnant) and
      attached to a Langendorf's apparatus. Heart rate, left ventricular systolic
      pressure, and contractility were measured. Hearts were exposed serially to 2, 4,
      and 6 mU/ml concentrations of oxytocin. The experiment was repeated in 15
      pregnant animals at a magnesium level of 5 mEq/L. RESULTS: Hearts from pregnant
      rats had lower heart rates than did hearts from nonpregnant animals. Oxytocin
      exposure diminished heart rate but increased left ventricular systolic pressure
      and contractility in a dose-dependent manner. Pregnancy did not alter this
      response. Magnesium levels of 5 mEq/L reversed the effects of oxytocin on
      contractility and left ventricular systolic pressure. CONCLUSION: Oxytocin is a
      negative chronotropic and positive inotropic agent in hearts from pregnant and
      nonpregnant rats. Magnesium reserves the positive inotropic effects of oxytocin.

PMID- 9240590
TI  - Endometrial resection versus vaginal hysterectomy for menorrhagia: long-term
      clinical and quality-of-life outcomes.
AB  - OBJECTIVE: Our purpose was to compare patients' satisfaction with the effect of
      treatment, health-related quality of life, psychologic status, and sexual
      functioning 2 years after endometrial resection or vaginal hysterectomy for
      menorrhagia. STUDY DESIGN: Menorrhagic women < or = 50 years old with a mobile
      uterus smaller than a 12-week pregnancy were enrolled in a randomized trial to
      compare endometrial resection and vaginal hysterectomy. Two years after surgery
      the women were requested to rate the degree of satisfaction with the effect of
      the operation and to complete the Short Form 36 general health survey
      questionnaire, the Hospital Anxiety and Depression Scale, and the revised
      Sabbatsberg Sexual Rating Scale. RESULTS: Forty-one subjects underwent
      endometrial resection and 44 underwent vaginal hysterectomy without major
      complications. Of the 77 women attending the 2-year follow-up visit, 33 of 38
      (86.8%) in the endometrial resection arm were very satisfied or satisfied with
      the treatment compared with 37 of 39 (94.8%) of those in the hysterectomy arm.
      According to the Short Form 36 questionnaire, social functioning and vitality
      scores were significantly better in the hysterectomy group than in the resection
      group. Significantly lower Hospital Anxiety and Depression Scale anxiety scores
      were observed in the former than in the latter subjects. The Sabbatsberg Sexual
      Rating Scale scores were similar in the two groups. CONCLUSIONS: In patients
      requiring surgical treatment for menorrhagia vaginal hysterectomy appeared
      slightly more satisfying and offered a better health-related quality of life than
      did endometrial resection at 2-year follow-up. Hysterectomy did not adversely
      affect psychologic status and sexual functioning.

PMID- 9240591
TI  - Ultrasonography-based triage for perimenopausal patients with abnormal uterine
      bleeding.
AB  - OBJECTIVE: Abnormal perimenopausal bleeding is common and accounts for much
      medical and surgical intervention. This study was undertaken to evaluate an
      ultrasonography-based triage paradigm for perimenopausal patients with abnormal
      uterine bleeding. STUDY DESIGN: Four hundred thirty-three perimenopausal patients
      with abnormal uterine bleeding (either metrorrhagia, menorrhagia, or both) were
      evaluated. In lieu of undergoing a sampling procedure they were brought back on
      days 4 to 6 of the subsequent bleeding cycle, when the endometrium was expected
      to be its thinnest. If a distinct endometrial echo < or = 5 mm (double layer) was
      imaged by endovaginal ultrasonography, dysfunctional uterine bleeding was
      diagnosed. If a thickened endometrial echo > 5 mm or no endometrial echo was
      reliably visualized, a saline infusion sonohysterography was performed. If saline
      infusion sonohysterography revealed a symmetric single-layer endometrial
      thickness < 3 mm, dysfunctional uterine bleeding was diagnosed. If focal lesions
      were noted (polyps, submucous myomas, focal thickening), the patient was
      scheduled for curettage with hysteroscopy. If the endometrium was globally
      thickened, nondirected office biopsy was performed. RESULTS: A total of 341
      patients (79%) had ultrasonographic evidence of no anatomic abnormality, and
      dysfunctional uterine bleeding requiring no further studies was diagnosed. Fifty
      eight patients (13%) had focal polypold masses, all of which were removed
      hysteroscopically and confirmed pathologically. Twenty-two patients (5%) had
      submucous myomas; 10 patients (23%) had globally thickened endometrium on saline
      infusion sonohysterography, and then nondirected office sampling revealed
      hyperplasia in 5 and proliferation in 5. Two patients had technically inadequate
      saline infusion sonohysterography, and thus we proceeded to hysteroscopy with
      curettage. CONCLUSION: Nondirected office biopsy alone without imaging would have
      potentially missed the diagnosis of focal lesions such as polyps, submucous
      myomas, and focal hyperplasia in up to 80 patients (18%). Our clinical algorithm
      for perimenopausal patients with abnormal uterine bleeding used unenhanced
      endovaginal ultrasonography followed by saline infusion sonohysterography for
      selected patients. This approach allowed for no endometrial sampling, nondirected
      sampling, or directed sampling depending on whether the ultrasonography-based
      triage revealed no anatomic abnormalities, globally thickened endometrial tissue,
      or focal abnormalities, respectively.

PMID- 9240592
TI  - A randomized prospective study of laparoscopy and laparotomy in the management of
      benign ovarian masses.
AB  - OBJECTIVE: Our purpose was to compare the results of laparoscopy with laparotomy
      in the management of ovarian masses not suspected to be malignant. STUDY DESIGN:
      In a prospective randomized study 102 patients requiring surgical management of
      ovarian masses were randomly assigned to laparoscopy (52) or laparotomy (50) in a
      teaching hospital from July 1994 to September 1995. Inclusion criteria was tumor
      not suspected to be malignant with a diameter of < or = 10 cm as measured by
      ultrasonography. All operations were performed by trainees under the supervision
      of an experienced surgeon. Statistical analysis included t tests and chi2 tests.
      RESULTS: There were no differences in demographic characteristics between the two
      groups nor any difference in the size of ovarian masses, adnexal adhesion score,
      or frequency of bilateral disease. All the ovarian masses were benign.
      Endometriotic cysts and dermoid cysts were the most common disorder in the two
      groups. Cystectomy was performed in > 70% of cases in each group. Operating time
      was not increased with the laparoscopic approach, and the frequency of
      inadvertent rupture of the ovarian masses was just as high as in laparotomy. The
      laparoscopic approach was associated with a significant reduction in operative
      morbidity (odds ratio 0.34, 95% confidence interval 0.13 to 0.88), postoperative
      pain and analgesic requirement, hospital stay, and recovery period. Patients in
      general were satisfied with the operation, but significantly more patients were
      satisfied with the laparoscopy scar. CONCLUSION: Operative laparoscopy should
      replace laparotomy in the management of benign ovarian masses.

PMID- 9240593
TI  - Bone loss in elderly women prevented by ultralow doses of parenteral 17beta
      estradiol.
AB  - OBJECTIVES: Our purpose was to assess whether an ultralow dose of parental
      estradiol, aimed for treatment of vaginal atrophy, affects bone metabolism and
      bone density. STUDY DESIGN: Thirty healthy women > or = 60 years old were
      randomly assigned to a 6-month treatment with either an ultralow dose of
      parenteral estradiol (7.5 microg/24 hours) delivered by vaginal rings or no
      treatment in the proportion 2:1. RESULTS: Forearm bone density increased in
      estradiol users by 2.1% (95% confidence interval 0.4 to 3.8, p = 0.008),
      contrasting to a decrease in nonusers of -2.7% (95% confidence interval -5.9 to
      0.4, p = 0.077). In analysis of variance the changes in the two study groups
      differed significantly (p = 0.0004). Consistently, serum alkaline phosphatases,
      bone-specific alkaline phosphatases, and osteocalcin concentrations decreased in
      the treatment group (8%, p = 0.019; 14%, p = 0.0006; and 9%, p = 0.02,
      respectively), suggesting reduced bone turnover. No significant changes were
      found in nonusers. CONCLUSION: Ultralow doses of estradiol may potentially
      prevent bone loss in women > or = 60 years old.

PMID- 9240595
TI  - Prevalence and impact of cyclic mastalgia in a United States clinic-based sample.
AB  - OBJECTIVES: A descriptive study was conducted to examine the prevalence of
      premenstrual breast symptoms, the impact of cyclic mastalgia on various
      activities, and associated patterns of health care utilization. STUDY DESIGN:
      Patients at an obstetrics and gynecology clinic (n = 1171) completed a
      questionnaire. RESULTS: Sixty-nine percent of women reported regular premenstrual
      discomfort; 36% had consulted a health care provider about the symptoms. Current
      moderate-to-severe cyclic mastalgia was found in 11%. Women <36 years old with
      cyclic mastalgia were 4.7 times as likely as asymptomatic young women to have had
      a mammogram. Mastalgia interferes with usual sexual activity in 48% of women and
      with physical (37%), social (12%), and work or school (8%) activity. CONCLUSIONS:
      Cyclic mastalgia is a common problem, sometimes severe enough to interfere with
      usual activities, and it is associated with high use of mammography among young
      women. Largely ignored both scientifically and clinically in the United States,
      this disorder merits further biopsychosocial investigation.

PMID- 9240594
TI  - Molecular profile of advanced-stage transitional cell carcinoma of the ovary.
AB  - OBJECTIVES: Our purpose was to determine the molecular profile of advanced-stage
      transitional cell carcinoma in terms of immunostaining for p53, epidermal growth
      factor receptor and HER-2/neu, deoxyribonucleic acid index, and S-phase fraction
      and to analyze the prognostic significance of these markers. STUDY DESIGN:
      Archival paraffin-embedded tissue blocks from 29 advanced stage transitional cell
      carcinomas were obtained. Selected sections of the primary tumors were
      immunostained for p53, epidermal growth factor receptor, and HER-2/neu;
      deoxyribonucleic acid ploidy and S-phase fraction were determined with use of
      flow cytometry. Clinical information was abstracted from the medical records.
      Survival times were analyzed according to the life-table methods of Kaplan and
      Meier, and the statistical significance of the various factors was tested with
      the log-rank test. The proportional hazards model of Cox was used to identify
      prognostic factors. RESULTS: Positive immunostaining was observed for p53 in 13
      cases (45%), for epidermal growth factor receptor in 14 cases (50%), and for HER
      2/neu in 19 cases (65%). Tumors were diploid in 16 cases (55%) and aneuploid in
      13 (45%). The S-phase fraction was < or = 15% (mean) in 13 cases (45%) and > 15%
      in 16 cases (55%). The median survival for the entire group was 52 months. None
      of the above variables had a significant effect on survival time. CONCLUSION:
      Neither immunostaining for p53, epidermal growth factor receptor, and HER-2/neu
      nor deoxyribonucleic acid ploidy nor S-phase fraction allowed us to distinguish
      transitional cell carcinoma from other more common epithelial ovarian cancers. In
      addition, no prognostic significance was associated with these biomarkers. A
      study of larger numbers of cases may be more elucidative.

PMID- 9240596
TI  - The differential expression of the HER-2/neu oncogene among high-risk human
      papillomavirus-infected glandular lesions of the uterine cervix.
AB  - OBJECTIVE: Our purpose was to examine the relationship between HER-2/neu
      expression and human papillomavirus infection in cervical glandular neoplasia.
      STUDY DESIGN: Cases of cervical adenocarcinoma in situ and invasive
      adenocarcinoma were selected for study. Human papillomavirus typing was performed
      by in situ hybridization. HER-2/neu was detected by in situ hybridization and
      immunohistochemistry. Fisher's exact test was used to assess for statistical
      significance. RESULTS: Fifteen cases of adenocarcinoma in situ and invasive
      adenocarcinoma were analyzed. In situ hybridization detected HER-2/neu messenger
      ribonucleic acid in 8 cases, whereas immunohistochemistry detected protein in 5
      cases. Overall, HER-2/neu activity was present in 10 cases (66.7%). HER-2/neu
      messenger ribonucleic acid was detected more commonly in lesions associated with
      human papillomavirus type 16 versus type 18 (85.7% vs 25.0%, p = 0.04).
      CONCLUSION: HER-2/neu is frequently expressed in human papillomavirus-infected
      glandular lesions of the cervix. In situ hybridization may provide a more
      sensitive indicator of HER-2/neu activity over immunohistochemistry. Preferential
      expression of HER-2/neu messenger ribonucleic acid was detected in human
      papillomavirus type 16 versus type 18 lesions. Further study is warranted to
      examine relationships between human papillomavirus infection and HER-2/neu
      expression.

PMID- 9240597
TI  - The labor-adjusted cesarean section rate--a more informative method than the
      cesarean section "rate" for assessing a practitioner's labor and delivery skills.
AB  - OBJECTIVE: Our purpose was to determine the benefits of an acuity-adjusted labor
      management tool. STUDY DESIGN: A retrospective review was performed of all
      deliveries at Good Samaritan Regional Medical Center in Phoenix, Arizona, for a 1
      year period from Jan. 1 to Dec. 31, 1994. All physicians with > or = 20
      deliveries were included in the analysis. Patients with indications for which
      most practitioners would perform a cesarean delivery were removed from
      consideration. Physicians were then compared with respect to labor management in
      the remaining patients without relative contraindications to vaginal delivery.
      RESULTS: The total number of deliveries (n = 6062) was performed by 47 attending
      obstetricians, 9 perinatologists, an obstetrics-gynecology clinic, and a family
      practice clinic. The "raw" cesarean section rate was 20.1%. Those at high risk
      for cesarean delivery (n = 534) were excluded, leaving 684 cesarean sections
      performed in 5528 patients (12.4%) who were appropriate to labor. Differences
      were observed between the nulliparous cesarean section rate (16%) compared with
      that for parous patients (10.1%) (p < 0.0001 by Fisher's exact test (two-tailed)
      but not between attending obstetrician-gynecologists (12.4%) and perinatologists
      (13.8%) (not significant). CONCLUSION: A labor-adjusted cesarean section rate is
      more appropriate than just "raw" data. Medical, obstetric, and fetal factors
      affect a "raw" rate that is out of the control of the obstetrician. This method
      of assessing the labor and delivery skills of each practitioner and hospital
      would allow meaningful comparison with others.

PMID- 9240598
TI  - The case for trial of labor in the patient with a prior low-segment vertical
      cesarean incision.
AB  - OBJECTIVE: Our purpose was to review recent obstetric literature detailing the
      subsequent delivery experience of patients with a prior low-segment vertical
      cesarean incision and to derive recommendations for practice on the basis of this
      information. STUDY DESIGN: Ten studies that included information about pregnancy
      outcome in patients with prior low-segment vertical cesarean operations were
      retrieved and reviewed from the American obstetric literature since 1981 and from
      a review of all abstracts presented annually since 1981 to the Society of
      Perinatal Obstetricians. RESULTS: Altogether, information about subsequent
      pregnancy outcome for 382 patients with prior low-segment vertical cesarean
      delivery was available for analysis. Among the 372 patients with complete patient
      population information, vaginal delivery was safely accomplished in 306 (82%).
      Four uterine ruptures (1.05%) have been reported, only one of which occurred
      after a single prior unextended low-segment vertical cesarean incision. Two
      ruptures occurred elsewhere on the lateral or posterior aspect of the uterus in
      subsequent pregnancies, and the fourth rupture occurred at the juncture of prior
      low vertical and transverse incisions. No perinatal mortality or permanent
      perinatal morbidity was encountered with these pregnancies. CONCLUSIONS: In the
      otherwise uncomplicated pregnancy the patient with one previous nonextended low
      segment vertical cesarean incision should be considered to have a prior low
      segment scar and as such be a candidate for trial of labor in her current
      singleton pregnancy. The same care, counseling, and caution should be exercised
      for this patient as for one with a prior low-segment transverse incision.

PMID- 9240599
TI  - Maternal characteristics and risk of severe neonatal thrombocytopenia and
      intracranial hemorrhage in pregnancies complicated by autoimmune
      thrombocytopenia.
AB  - OBJECTIVE: The antenatal and intrapartum management of women with autoimmune
      thrombocytopenia is controversial. The current approach emphasizes an effort to
      identify maternal characteristics predictive of severe neonatal thrombocytopenia
      or to measure fetal platelet counts and perform cesarean section in patients
      considered to be at risk for neonatal intracranial hemorrhage. In the current
      study we review our experience with maternal autoimmune thrombocytopenia and
      neonatal outcome. STUDY DESIGN: Fifty-five pregnancies with autoimmune
      thrombocytopenia over a 10-year period in three major medical centers in San
      Diego, California, were evaluated. Maternal characteristics and neonatal outcomes
      were assessed and compared with those in other recent reports. Data were
      submitted to Fisher's exact (two-tailed), chi2, and Student t tests, with linear
      regression performed to analyze the association between variables. RESULTS:
      Maternal characteristics including platelet count, presence of antiplatelet
      antibody, antecedent history of autoimmune thrombocytopenia, and corticosteroid
      therapy were not predictive of severe neonatal thrombocytopenia. Maternal history
      of splenectomy was significantly correlated with fetal platelet counts <50 x
      10(9)/L (odds ratio 5.63; 95% confidence interval 2.2 to 14.3). There were four
      neonates with severe neonatal thrombocytopenia (8%), and one who was delivered by
      cesarean section had intracranial hemorrhage. CONCLUSIONS: These findings,
      combined with others in the literature, confirm that severe neonatal
      thrombocytopenia is an infrequent complication of maternal autoimmune
      thrombocytopenia and is not reliably predicted by maternal characteristics.
      Intracranial hemorrhage is also a rare event and is not related to mode of
      delivery. Cesarean section should be reserved for obstetric indications only.

PMID- 9240600
TI  - The paradoxical effect of smoking in preeclamptic pregnancies: smoking reduces
      the incidence but increases the rates of perinatal mortality, abruptio placentae,
      and intrauterine growth restriction.
AB  - OBJECTIVES: Smoking is associated with a reduced risk of preeclampsia, but what
      is the outcome of pregnancy when preeclampsia develops in women who smoke? STUDY
      DESIGN: Single births in Sweden from 1987 through 1993 to nulliparous women aged
      15 to 34 years (N = 317,652) were included. Poisson regression analyses were used
      to calculate adjusted relative risks and rates of adverse pregnancy outcomes.
      RESULTS: Maternal smoking was associated with significantly reduced risks of mild
      and severe preeclampsia (relative risks = 0.6 and 0.5, respectively). In
      pregnancies with severe preeclampsia, smoking at least 10 cigarettes per day was
      associated with increased rates of perinatal mortality (from 24 to 36 per 1000),
      abruptio placentae (from 31 to 67 per 1000), and being small for gestational age
      (from 28% to 68%), whereas the corresponding smoking-related increases in rates
      in nonhypertensive pregnancies were considerably less. CONCLUSIONS: Smokers in
      whom preeclampsia develops have very high risks of perinatal mortality, abruptio
      placentae, and small-for-gestational-age infants.

PMID- 9240601
TI  - Changes in activated protein C resistance during normal pregnancy.
AB  - OBJECTIVE: The objective of this study was to determine the changes in activated
      protein C resistance that occur during normal pregnancy. STUDY DESIGN: In this
      cross-sectional study activated protein C was measured in 128 women with normal
      pregnancies in the first, second, and third trimesters and in nonpregnant control
      subjects with 24 to 39 women in each group. In addition, factor V, factor VIII,
      free protein S, and functional protein C were measured and correlated with
      activated protein C levels. Polymerase chain reaction for factor V Leiden
      mutation was performed. RESULTS: There was a significant fall in the activity of
      activated protein C in the second and third trimesters of pregnancy (p < 0.05).
      This was related to increased factor VIII and decreased free protein S levels (p
      = 0.002, R2 = 0.20). The prevalence of the factor V Leiden mutation was 7.3%.
      CONCLUSION: Resistance to activated protein C is increased in the second and
      third trimesters of pregnancy. This is related to the alterations in other
      coagulation proteins, a phenomenon normally occurring during pregnancy.

PMID- 9240602
TI  - Activated protein C resistance and adverse pregnancy outcome.
AB  - OBJECTIVE: Activated protein C resistance is a genetic disorder that predisposes
      to thrombosis. Hyperestrogenism strongly increases the risk of thrombosis in
      affected individuals. Other thrombophilic disorders, such as the antiphospholipid
      antibody syndrome, have been associated with adverse pregnancy outcome, probably
      mediated by abnormal clotting in the placental circulation. The purpose of this
      series is to present clinical and laboratory data on individuals with a poor
      obstetric history and activated protein C resistance. STUDY DESIGN: Within an 18
      month period seven patients with more than five early pregnancy losses, recurrent
      intrauterine fetal deaths, intrauterine growth restriction, and early severe
      preeclampsia in association with activated protein C resistance came to our
      attention. The initial diagnosis was made by activated protein C ratios, and
      molecular diagnoses of activated protein C resistance genotypes were made by
      polymerase chain reaction for the factor V Leiden mutation. All patients had an
      extensive diagnostic workup for known etiologies of the above complications and
      other thrombophilic disorders. RESULTS: All patients had activated protein C
      ratios <1.7. Six patients were heterozygous for the Leiden mutation, and one
      patient was homozygous. A personal or family history of thromboembolism was
      present in one case and three cases, respectively. The diagnostic workup was
      otherwise unrevealing. One newborn was diagnosed of bilateral renal vein
      thrombosis on day 1 of life. CONCLUSIONS: Activated protein C resistance was
      found in association with extremely poor obstetric outcomes. A family or personal
      history of thromboembolism was suggestive in many cases. A population-based study
      is needed to determine the role of activated protein C resistance in adverse
      pregnancy outcome.

PMID- 9240603
TI  - Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies and
      pregnancies complicated by hypertensive disorders.
AB  - OBJECTIVE: Our objective was to compare maternal ophthalmic artery pulsatility
      index values in normotensive pregnancies and pregnancies complicated by
      hypertensive disorders. STUDY DESIGN: The ophthalmic artery in 17 normotensive
      nonpregnant women, 29 normotensive pregnant women, 9 patients with mild
      preeclampsia, 6 with severe preeclampsia, 6 with transient hypertension, and 9
      with chronic hypertension was studied with color Doppler flow imaging and pulsed
      Doppler ultrasonography. The mean arterial blood pressure and the ophthalmic
      artery pulsatility index were calculated in each group. RESULTS: The pulsatility
      index (1.17 +/- 0.08) in severe preeclampsia was lowest among the groups p <
      0.05), whereas that (2.92 +/- 0.59) in normotensive pregnant women was highest
      among the groups (p < 0.05). The pulsatility index (1.47 +/- 0.30) in mild
      preeclampsia was significantly lower than that (1.89 +/- 0.27) in transient
      hypertension (p < 0.05). There was no significant difference in pulsatility index
      between mild preeclampsia and chronic hypertension (1.69 +/- 0.49) or between
      transient hypertension and chronic hypertension. The pulsatility index inversely
      correlated well with the mean arterial blood pressure (R2 = 0.645, p < 0.0001).
      CONCLUSIONS: These results suggest that the lower pulsatility index should be
      interpreted as orbital vascular vasodilation, indicating orbital hyperperfusion
      or hyperemia. Changes in pulsatility index in the ophthalmic artery may be
      indicative of similar changes in other cerebral vessels.

PMID- 9240604
TI  - Changes in activity of cytosolic phospholipase A2 in human amnion at parturition.
AB  - OBJECTIVE: The purpose of this study was to determine whether increased cytosolic
      phospholipase A2 activity mediated arachidonic acid mobilization for
      prostaglandin synthesis in amnion at parturition. STUDY DESIGN: Amnion was
      collected immediately after delivery from four groups of patients: preterm (<37
      weeks) with no labor or labor and term (>37 weeks) with no labor or labor and
      stored at -70 degrees C. Tissues were homogenized and centrifuged for 1 hour at
      100,000 g, and cytosol was assayed for cytosolic phospholipase A2 activity with
      use of carbon 14-labeled 1-stearoyl-2 arachidonyl phosphatidylcholine plus 10
      micromol/L unlabeled substrate and 5 mmol/L calcium in 10 mmol/L N-2
      hydroxyethylpiperazine-N-2-ethanesulfonic acid, pH 7.4. Incubations were
      performed in duplicate +/- 10 micromol/L arachidonyl trifluoromethyl ketone, a
      specific inhibitor of cytosolic phospholipase A2 activity, at 30 degrees C for 45
      minutes. RESULTS: Total cytosolic phospholipase A2 activity (in picomoles of
      arachidonic acid per minute per milligram of protein) calculated as the
      difference between the activity in the presence and absence of arachidonyl
      trifluoromethyl ketone was (mean +/- SE) as follows: preterm no labor (n = 7)
      8.94 +/- 3.08, preterm with labor (n = 6) 6.79 +/- 2.31, term no labor (n = 7)
      14.85 +/- 1.66, and term with labor (n = 5) 5.51 +/- 1.52. Enzyme activity
      increased with gestational age and was highest in the term no labor group. A
      significant decrease in cytosolic phospholipase A2 activity occurred with labor
      (p < 0.05). The greatest decrease in activity was in the term group (p < 0.05).
      CONCLUSION: Total cellular cytosolic phospholipase A2 activity in amnion is
      highest in anticipation of labor but during labor total activity is depleted,
      resulting in the low activity measured after delivery of the placenta. The
      substrate specificity and changes in amnion total cytosolic phospholipase A2
      activity with labor strongly suggests a role in mediation of arachidonic acid
      mobilization and prostaglandin synthesis at labor.

PMID- 9240605
TI  - Failure of magnesium sulfate infusion to inhibit uterine activity in pregnant
      sheep.
AB  - OBJECTIVES: Our purpose was to determine the effect of magnesium sulfate infusion
      on nonlabor uterine contractures and corticotropin-induced preterm uterine
      contractions in pregnant sheep. STUDY DESIGN: Fetal and maternal vascular
      catheters and uterine electromyographic electrodes were surgically placed in 15
      pregnant sheep between 118 and 125 days' gestation. After 3 to 5 days of
      recovery, magnesium sulfate was infused into 7 ewes with a 0.11 gm/kg bolus over
      20 minutes, followed by 0.08 gm/kg/hr. In 8 animals labor was induced with use of
      an intrafetal corticotropin infusion, after which 4 ewes received magnesium
      sulfate and 4 received saline solution. Continuous recordings of uterine
      electromyographic activity, amniotic pressure, fetal heart rate, blood pressure,
      and tracheal pressure were made. Maternal and fetal magnesium, calcium, albumin
      concentrations, and blood gases were determined before and during the infusion.
      RESULTS: Maternal magnesium concentrations increased from an average of 0.94 +/-
      0.03 mmol/L to 2.73 +/- 0.1 mmol/L at the end of the bolus, remaining elevated
      (2.44 +/- 0.17 mmol/L) for 8 hours. Fetal magnesium concentrations (0.89 +/- 0.03
      mmol/L before the bolus) did not change with the maternal infusion. In ewes not
      in labor, uterine contractures occurred 3.7 +/- 0.7 times per 2 hours before and
      did not change significantly with the infusion of magnesium sulfate. During
      corticotropin-induced preterm labor uterine contractions were present 13 +/- 3.2
      times per hour before infusions and were unchanged by infusion of magnesium
      sulfate to the ewes. CONCLUSIONS: Magnesium sulfate infusion in pregnant sheep
      has no effect on either nonlabor uterine contractures or on corticotropin-induced
      preterm uterine contractions.

PMID- 9240606
TI  - A randomized controlled trial of strict glycemic control and tertiary level
      obstetric care versus routine obstetric care in the management of gestational
      diabetes: a pilot study.
AB  - OBJECTIVES: The purpose of this study was to determine whether strict maternal
      glycemic control for the treatment of gestational diabetes lessened the risk of
      fetal macrosomia, birth trauma, neonatal hypoglycemia, and operative delivery.
      The aim of the pilot study was to prepare for a multicenter trial by assessing
      patient acceptance of the study, by determining realistic accrual rates, and by
      detecting any major adverse outcomes in the control group that received routine
      obstetric care. STUDY DESIGN: The study was a prospective randomized controlled
      trial comparing fetal-neonatal and maternal outcomes in 300 women with
      gestational diabetes. Women randomized to the treatment arm were managed by
      strict glycemic control and tertiary level obstetric care, and women in the
      control arm received routine obstetric care. RESULTS: Three hundred women with
      gestational diabetes mellitus were studied. There was no difference in maternal
      age, weight, or length of gestation between groups. The treatment mean birth
      weight was 3437 +/- 575 gm compared with 3544 +/- 601 gm in the control group, a
      difference of 107 gm (not significant). Macrosomia rates were similar. There was
      no birth trauma in either group. The frequency of neonatal hypoglycemia and other
      metabolic complications was the same. The mode of delivery also showed similar
      patterns. The treatment group had significantly lower preprandial and
      postprandial glucose levels by 32 weeks' gestation, which continued to term.
      CONCLUSION: This pilot study suggests that intensive treatment of gestational
      diabetes mellitus may have little effect on birth weight, birth trauma, operative
      delivery, or neonatal metabolic disorders. It has demonstrated the safety of
      proceeding to a multicenter trial of sufficient sample size to confirm these
      findings.

PMID- 9240608
TI  - Clinical risk factors for placenta previa-placenta accreta.
AB  - OBJECTIVE: Our purpose was to define the clinical risk factors associated with
      placenta previa-placenta accreta. STUDY DESIGN: Hospital records were reviewed of
      all cases of placenta accreta confirmed histologically between January 1985 and
      December 1994. Additionally, we reviewed the records of all women with placenta
      previa and all those undergoing cesarean hysterectomy during the same period.
      Multiple logistic regression analysis was used to identify independent clinical
      risk factors for placenta accreta. RESULTS: Among 155,670 deliveries, 62 (1/2510)
      were complicated by histologically confirmed placenta accreta. Placenta accreta
      occurred in 55 of 590 (9.3%) women with placenta previa and in 7 of 155,080
      (1/22,154) without placenta previa (relative risk 2065, 95% confidence interval
      944 to 4516, p < 0.0001). Among women with placenta previa, advanced maternal age
      (> or = 35 years) and previous cesarean delivery were independent risk factors
      for placenta accreta. Placenta accreta was present in 36 of 124 (29%) cases in
      which the placenta was implanted over the uterine scar and in 4 of 62 (6.5%)
      cases in which it was not (relative risk 4.5, 95% confidence interval 1.68 to
      12.07). Among women with placenta previa, the risk of placenta accreta ranged
      from 2% in women < 35 years old with no previous cesarean deliveries to almost
      39% in women with two or more previous cesarean deliveries and an anterior or
      central placenta previa. CONCLUSION: Placenta accreta occurs in approximately 1
      of 2500 deliveries. Among women with placenta previa, the incidence is nearly
      10%. In this high-risk group advanced maternal age and previous cesarean section
      are independent risk factors.

PMID- 9240607
TI  - 17beta-Estradiol, progesterone, and testosterone inversely modulate low-density
      lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and
      macrophages.
AB  - OBJECTIVES: We have previously shown that low-density lipoprotein oxidation is
      diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In
      these experiments we wished to learn whether sex hormone effects on low-density
      lipoprotein oxidation alter placental cell viability in primary tissue culture.
      STUDY DESIGN: Primary tissue culture of human term placental cells was performed.
      RESULTS: Addition of 17beta-estradiol decreased low-density lipoprotein oxidation
      (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low
      density lipoprotein electrophoretic mobility) and placental cell toxicity
      (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p
      < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and
      testosterone increased low-density lipoprotein oxidation and chromium 51 release,
      the latter a maximum of 28% and 18%, respectively, for progesterone and
      testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts
      (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low
      density lipoprotein oxidation and estradiol, progesterone, and testosterone
      concentrations. CONCLUSIONS: Estradiol inhibits placental macrophage- and
      trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas
      progesterone and testosterone promote these effects. Sex steroid hormones may
      modulate the effects of oxidative stress on placental function in pregnancy.

PMID- 9240609
TI  - Myoendometrial versus placental uterine arteries: structural, mechanical, and
      functional differences in late-pregnant rabbits.
AB  - OBJECTIVE: This study compared late-pregnant radial uterine arteries that
      supplied the placenta versus the myoendometrium to evaluate differences in active
      and passive mechanical properties. STUDY DESIGN: Pressurized segments of
      placental versus myoendometrial radial uterine arteries from late-pregnant (day
      28 to 30) New Zealand White rabbits (n = 12) were compared in vitro for
      differences in luminal diameter, wall thickness, distensibility, and intrinsic
      tone as a function of transmural pressure. RESULTS: Both types of arteries
      responded to increased transmural pressure with active vasoconstriction; however,
      the amount of tone present in myoendometrial arteries was significantly greater
      than in placental arteries (percent tone at 75 mm Hg = 39% +/- 3% for
      myoendometrial versus 31% +/- 2% for placental arteries, p < 0.01). Measurements
      of unpressurized, fully relaxed arteries revealed that placental arteries were
      38% larger in diameter and had thicker walls than myoendometrial arteries did.
      However, myoendometrial arteries were significantly more distensible at
      transmural pressures >5 mm Hg. CONCLUSIONS: The increased size and diminished
      tone of placental compared with adjacent myoendometrial arteries would favor
      increased blood flow to the placenta; differences in size and passive mechanical
      properties suggest that a localized factor(s) originating from the fetus or
      placenta contributes to the gestational enlargement of those arteries that
      perfuse the placenta.

PMID- 9240610
TI  - Oxytocin enhances action potentials in pregnant human myometrium--a study with
      microelectrodes.
AB  - OBJECTIVE: Our purpose was to quantitatively assess the effects of oxytocin on
      membrane properties in the pregnant human myometrium. STUDY DESIGN: Specimens
      were obtained from the lower uterine segment during cesarean section at term.
      Electrical activity was recorded from individual cells by a conventional
      microelectrode method and the membrane functions were analyzed. RESULTS: Two
      types of spontaneous action potentials were seen: a long plateau potential and a
      spike-like action potential. With no change in the resting membrane potential,
      low concentrations of oxytocin either evoked an action potential with a plateau
      phase, increased the amplitude and duration of the plateau potential, or
      increased the frequency of generation of action potentials. Oxytocin also lowered
      the threshold for evoking an action potential. Higher concentrations depolarized
      the membrane with an associated reduction in membrane resistance. CONCLUSION:
      Oxytocin augments the excitability of pregnant human myometrial cells by multiple
      actions on the membrane, affecting both frequency and amplitude of action
      potentials.

PMID- 9240611
TI  - Variable effects on murine pregnancy of immunoglobulin G fractions from women
      with antiphospholipid antibodies.
AB  - OBJECTIVE: Initial studies showed that passive immunization with human
      immunoglobulin G fractions containing antiphospholipid antibodies can result in
      murine fetal loss. We intended to use the murine model to study mechanisms of
      fetal loss associated with antiphospholipid antibodies. However, we have since
      found variable effects of antiphospholipid antibodies on murine pregnancy. The
      objective of this study was to determine the consistency of murine pregnancy loss
      from antiphospholipid antibody containing immunoglobulin G fraction. STUDY
      DESIGN: Pregnant C3H/HeN (mated with C57B1/6 males) and BALB/c (mated with BALB/c
      males) mice were passively immunized with antiphospholipid antibody containing
      human immunoglobulin G fraction from 20 women with antiphospholipid syndrome. The
      mice received either a single dose of 10 to 30 mg on day 12 of pregnancy or 10 mg
      per day on days 12 to 14 of gestation. Some mice receiving each dose of
      immunoglobulin G fraction were bled to confirm serum levels of anticardiolipin
      antibodies. Mice were killed on day 15 and the fetal status was determined.
      RESULTS: Overall, passive immunization with individual antiphospholipid antibody
      containing immunoglobulin G fractions resulted in 801 live pups (75%), 232 fetal
      deaths (22%), and 38 resorptions (3%) in 131 mice. The effect of immunoglobulin G
      fractions from individual patients was highly variable. Immunoglobulin G fraction
      from eight women resulted in high rates of fetal loss. However, in spite of high
      levels of anticardiolipin antibodies, fetal outcome was normal in mice immunized
      with immunoglobulin G fraction from the majority of women. The rate of fetal
      death did not uniformly increase with increasing doses of immunoglobulin G
      fraction and was unrelated to the donor's medical history. Fetal outcome was
      similar for both C3H/HeN and BALB/c mice. CONCLUSIONS: Human antiphospholipid
      antibodies have variable effects on murine pregnancy outcome. Characterization of
      antiphospholipid antibodies that do and do not cause murine fetal loss may
      provide insight into epitopes relevant to fetal loss associated with
      antiphospholipid syndrome.

PMID- 9240612
TI  - Longitudinal study of beta- and alpha-adrenergic receptor properties during human
      pregnancy.
AB  - OBJECTIVE: Our goal was to ascertain whether alterations in beta- and alpha
      adrenergic receptor number and function (cyclic adenosine monophosphate
      production) occur during and after pregnancy. Because the actions of beta- and
      alpha2-adrenergic receptors tend to oppose each other, we hypothesized that there
      might be progressive, possibly reciprocal changes in these receptors during and
      after pregnancy. STUDY DESIGN: Blood was obtained from 21 women at 10, 20, 30,
      and 37 weeks of pregnancy and 3 to 4 months post partum. Lymphocyte beta- and
      platelet alpha2-adrenergic receptor number and affinity were quantified by
      radioligand binding studies, and receptor function was assessed by cyclic
      adenosine monophosphate generation assays. RESULTS: Although there were
      suggestions of progressive alterations in some of the variables studied, beta-
      and alpha2-adrenergic receptor number, affinity, and function did not manifest
      any statistically significant changes. CONCLUSION: Pregnancy did not produce
      marked alterations in beta-adrenergic receptor or alpha2-adrenergic receptor
      properties.

PMID- 9240613
TI  - Cyclin-dependent kinase inhibitor p21 in endometrial carcinoma.

PMID- 9240614
TI  - Preeclampsia and diabetes.

PMID- 9240615
TI  - Hypothesis of preeclampsia requires inclusion of the role of platelets.

PMID- 9240616
TI  - The complementary role of echoplanar magnetic resonance imaging and three
      dimensional ultrasonography in fetal lung assessment.

PMID- 9240617
TI  - A new ethical and clinical dilemma in obstetric practice: cesarean section "on
      maternal request".

PMID- 9240618
TI  - The preoperative evaluation of ovarian tumors can be improved?

PMID- 9240619
TI  - Do we really have a reproducible classification system for pelvic organ prolapse?

PMID- 9240620
TI  - Cesarean birth epidemics.

PMID- 9240621
TI  - Phytosterolaemia: diagnosis, characterization and therapeutical approaches.
AB  - Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage
      disease characterized by tendon and tuberous xanthomas and by a strong
      predisposition to premature coronary atherosclerosis. In addition to increased or
      normal serum cholesterol, patients are found to have markedly elevated
      concentrations of the phytosterols sitosterol and campesterol. These sterols
      accumulate in all tissues, except the brain. Increased intestinal absorption of
      plant sterols, impaired biliary excretion, and decreased cholesterol synthesis
      are suggested as causes for this disease. However, the primary defect has not yet
      been identified. As well as dietary restrictions of cholesterol and plant
      sterols, therapeutic approaches based on interruption of the enterohepatic
      circulation of bile acids by administration of bile acid-binding resins or ileal
      bypass surgery have been recommended as therapeutic approaches to reduce all
      serum sterols. Administration of sitostanol, a nonabsorbable saturated plant
      sterol, showed a significant reduction of serum plant sterols and cholesterol in
      two patients with phytosterolaemia, presumably by competitive inhibition of
      sterol absorption.

PMID- 9240623
TI  - The thyroid and breast cancer: a significant association?
AB  - The coincidence of thyroid disorders and breast cancer has long been a subject of
      debate. Associations with hyperthyroidism, hypothyroidism, thyroiditis and
      nontoxic goitre have been reported. Although no convincing evidence exists of a
      causal role for overt thyroid disease in breast cancer, the preponderance of
      published work favours an association with hypothyroidism. Geographical
      variations in the incidence of breast cancer have been attributed to differences
      in dietary iodine intake and an effect of iodide on the breast has been
      postulated. Recent reports have shown a direct association between thyroid
      enlargement, as assessed by ultrasound, and breast cancer. Although the exact
      mechanism for the demonstrated association between diseases of the thyroid and
      breast cancer remains to be elucidated, there is at least the possibility that
      the presence of thyroid abnormalities may influence breast cancer progression and
      this alone should stimulate awareness into the coincidence of the two disorders.

PMID- 9240622
TI  - Type 1 and type 2 cytokines in HIV infection -- a possible role in apoptosis and
      disease progression.
AB  - The progression of HIV-infected subjects to AIDS was recently postulated to be
      controlled by the balance between type 1 cytokines (mainly enhancing cell
      mediated immunity) and type 2 cytokines (mainly augmenting antibody production).
      Thus, progression of HIV infection was suggested to be accompanied by a decline
      of in vitro production of interleukin-2 (IL-2), IL-12 and interferon gamma (IFN
      gamma) (type 1 cytokines) and an increase in the production of IL-4, IL-5, IL-6
      and IL-10 (type 2 cytokines) by peripheral blood mononuclear cells of HIV
      seropositive patients. According to this hypothesis, clinical markers of
      progression would be considered the loss of the ability to elicit a delayed-type
      hypersensitivity reaction to ubiquitous antigens (secondary to defective IL-2
      production), hyper-IgE (secondary to increased IL-4 production) and
      hypereosynophilia (secondary to increased IL-5 production). The type 1 to type 2
      shift was suggested to be predictive for the following events: (i) reduction in
      CD4 counts; (ii) time to AIDS diagnosis; (iii) time to death. Support for this
      hypothesis stems from the recent observation that a strong type 1/weak type 2
      cytokine production profile was observed in HIV-seropositive patients with
      delayed or absent disease progression, whereas progression of HIV infection was
      characterized by a weak type 1/strong type 2 cytokine production profile. PBMC of
      HIV-seropositive individuals are susceptible to antigen-induced cell death (AICD)
      after antigen recognition via T-cell receptor (TcR). While TcR-induced AICD is
      seen in CD4+ and CD8+ cells programmed cell death induced by recall antigens is
      preferentially observed in CD4+ cells, a situation more closely resembling the
      CD4 depletion of HIV infection. Because type 1 cytokines reduce, whereas type 2
      cytokines augment T-lymphocyte AICD, an increase in the concentration of type 2
      cytokines could result in the decline in CD4+ cells seen in HIV infection.

PMID- 9240624
TI  - Atherosclerosis and the mouse: a decade of experience.
AB  - Atherosclerotic disease is the leading killer in Western societies, accounting
      for close to 50% of deaths. Relatively little is known about the genetics of this
      disease in the general population despite its high prevalence. Several
      experimental systems exist for studying the pathology of this disease, but these
      larger animal models fail to offer insights into the genetics. Over the past
      decade the mouse has supplanted larger animal models of atherosclerosis to become
      the primary organism for the study of atherosclerosis genetics and, to some
      extent, pathophysiology. Lipoprotein biologists in particular have benefited from
      the ability to modify the mouse genetically to study the relationship of
      lipoprotein abnormalities to atherosclerosis. Given the complexity of the disease
      an in vivo system is requisite and since the mid-1980s the mouse has served as
      that system. Initial studies using classical mouse genetics first defined
      differing susceptibilities to atherosclerosis among distinct strains of mice.
      These studies acted at least in part to shed preconceptions among lipoprotein and
      vascular biologists that the mouse could not serve as an atherosclerosis model.
      Subsequent studies taking advantage of the ability to overexpress and knock genes
      out have advanced understanding of the in vivo function of genes involved in
      lipoprotein transport and the relationship between these genes (and their
      attendant lipoprotein disorders) and atherosclerotic disease. This review
      chronicles the advances made over the past 10 years and reviews the contribution
      that the mouse has provided lipoprotein and atherosclerosis research.

PMID- 9240626
TI  - Assisted reproductive technology: the state of the ART.
AB  - At least one in ten couples of reproductive age is affected by infertility. Tubal
      disease, ovulatory defects, endometrosis and abnormal sperm physiology are the
      most common causes of failure to conceive. Many of these disorders can be treated
      successfully with surgery, ovulation induction or intrauterine insemination, but
      in selected cases, or where there is long-standing intractable infertility,
      assisted reproductive technology (ART) becomes the treatment of choice. We
      provide an overview of the techniques for assisted reproduction, including in
      vitro fertilization, gamete intrafallopian transfer and other related procedures.
      Indications for treatment, patient evaluation and advances in reproductive
      technology including embryo cryopreservation, micromanipulation and donor gametes
      are also reviewed.

PMID- 9240625
TI  - Prevention of gonadal damage during cytotoxic therapy.
AB  - Infertility represents one of the main remote sequelae of cytotoxic chemotherapy
      given for various malignant diseases. The impairment of gonadal function after
      cytotoxic chemotherapy is more frequent in the male than in the female. Because
      dividing cells are more sensitive to the cytotoxic effects of alkylating agents
      than are cells at rest, it has been hypothesized that inhibition of the pituitary
      gonadal axis by gonadotropin-releasing hormone (GnRH) agonists would render the
      germinal epithelium less susceptible to the cytotoxic effects of chemotherapy.
      This hypothesis has not been thoroughly clinically tested until recently,
      although several investigators have demonstrated that GnRH-agonistic analogues
      (GnRH-a) inhibit chemotherapy-induced ovarian follicular depletion in the rat and
      Rhesus monkeys. Based on this rationale, we have undertaken a prospective
      evaluation to determine whether GnRH-a administration during combination
      chemotherapy for Hodgkin's and non-Hodgkin's lymphoma could prevent posttreatment
      ovarian damage in women by inducing a temporary prepubertal hormonal milieu.
      While over 93% of the surviving patients in the GnRH-a and chemotherapy group
      resumed spontaneous ovulation and menses, less than 40% of the women in the
      control group of chemotherapy without the GnRH-a cotreatment resumed normal
      ovarian cyclic activity. More than 60% of the women experienced premature ovarian
      failure (POF) in the chemotherapy alone group. Our preliminary results suggest
      that GnRH-a cotreatment protects against POF during cytotoxic chemotherapy. The
      GnRH-a and chemotherapy cotreatment may be also suggested for young women treated
      by cyclophosphamide pulse therapy or other gonadotoxic treatments for systemic
      lupus erythematosus, organ transplantation and other autoimmune diseases. The
      technology of cryopreservation of human ova for future fertility in these
      patients awaits clinical validation and substantiation. This review discusses
      possibilities to prevent gonadal damage induced by cytotoxic therapy and presents
      the clinical data currently available.

PMID- 9240627
TI  - Stress-related disturbances of the menstrual cycle.
AB  - Stress is a common cause of hypothalamic amenorrhoea. In our laboratory, we have
      studied the effects of an inflammatory-like stress on gonadotropin secretion and
      on the menstrual cycle in a nonhuman primate model. In this short review, we
      summarize some of our findings regarding the mechanisms whereby stress induces
      disturbances of reproductive function. Our data indicate that the hypothalamic
      pituitary-adrenal axis, through the release of corticotropin-releasing hormone
      and vasopressin, plays a mediatory role. One type of action is exerted through a
      central process resulting in the inhibition of the gonadotropin-releasing hormone
      pulse generator. The other type is mediated by a peripheral pathway stimulatory
      to gonadotropin secretion. Activation of one or the other pathway is determined
      by the ovarian endocrine milieu. Both actions presumably result in deleterious
      effects on the menstrual cycle.

PMID- 9240628
TI  - Oestrogen receptor variants and mutations in human breast cancer.
AB  - Several oestrogen receptor variant and mutated mRNA species have been identified
      in human breast samples and cell lines. Over-expression and altered expression of
      some of these mRNAs have been correlated with breast tumourigenesis and
      progression. The following review focuses on the current knowledge available in
      the scientific literature with respect to the type and characteristics of
      oestrogen receptor variants and mutations that have been identified as occurring
      naturally in human breast tissues and cell lines.

PMID- 9240629
TI  - Mitochondrial DNA and disease.
AB  - Mitochondrial diseases are a group of disorders characterized by morphological or
      functional defects of the mitochondria, the organelles producing most of our
      cellular energy. As the only extranuclear site carrying genetic information, the
      mitochondria add an important chapter into the inheritance patterns of genetic
      diseases. Mitochondrial DNA (mtDNA) is exclusively maternally inherited in
      humans, but a mitochondrial disorder may follow either maternal or Mendelian
      inheritance, depending on the site of the primary gene defect. After the initial
      finding of mtDNA mutations in rare ocular myopathies in 1988, an explosion in the
      amount of information on mitochondrial diseases has occurred. Because the
      mitochondria produce energy in all the tissues, symptoms resulting from mtDNA
      mutations may originate from any organ system, and the clinical spectrum of
      mitochondrial diseases has expanded to virtually all branches of medicine.
      Subgroups of several common diseases, such as diabetes, deafness and inherited
      cardiomyopathies, have been found to be caused by mtDNA mutations, and some mtDNA
      defects have been suggested to modify the outcome of diseases primarily caused by
      other factors, such as Parkinson's or Alzheimer's disease. Although no
      breakthroughs in the therapeutic trials on the devastating mitochondrial diseases
      have so far been achieved, detection of mtDNA mutations offers an accurate
      diagnosis and is a prerequisite for genetic counselling, being now accessible to
      most clinicians.

PMID- 9240630
TI  - Cyclo-oxygenase and colon cancer: clues to the aspirin effect?
AB  - Epidemiological and experimental studies indicate an inverse relationship between
      the risk of colon cancer development and intake of aspirin and other nonsteroidal
      anti-inflammatory drugs (NSAIDs). All NSAIDs are known inhibitors of cyclo
      oxygenase, the enzyme responsible for converting arachidonic acid to
      prostaglandins. Prostaglandins have been implicated in the pathogenesis of colon
      cancer and it has been suggested that the preventive effect of NSAIDs is due to
      inhibition of cyclo-oxygenase activity. Cyclo-oxygenase exists in two different
      isoforms, cyclo-oxygenase-1 and cyclo-oxygenase-2, and data obtained during the
      last few years have suggested that cyclo-oxygenase-2 might be involved in both
      human and experimental colon carcinogenesis. The purpose of this review is to
      provide an update on recent studies regarding cyclo-oxygenase, in particular
      cyclo-oxygenase-2, in relation to colon cancer in humans and in experimental
      models.

PMID- 9240631
TI  - How to define coronary heart disease in register-based follow-up studies:
      experience from the Helsinki Heart Study.
AB  - Information on coronary heart disease (CHD) obtained from the Finnish Hospital
      Discharge and Cause-of-Death Registers was compared with that collected in the
      Helsinki Heart Study (HHS) during an 8.5-year follow-up. The purpose of the
      comparison was two-fold, firstly, to study the accuracy of registration of CHD
      and secondly, to find out what diagnostic codes to use for CHD in register-based
      follow-up studies. The HHS cases were used as the 'golden standard' and the CHD
      deaths and definite nonfatal acute myocardial infarctions (AMIs) (all diagnoses)
      were taken from the registers to establish the sensitivity of the Hospital
      Discharge and Cause-of-Death Registers combined. The sensitivity was 0.84 during
      the period 1980-86 and 0.87 during 1987-90, with the positive predictive values
      0.94 and 0.92 respectively. The treatment effects seen in the HHS were compared
      with the effects that would have emerged, if register-based information only had
      been used with different definitions of CHD. Of the register-based calculations,
      the one with the definition 'all CHD deaths and hospitalizations with the ICD-8
      code 410' came closest to the HHS result, with a 32% reduction (P=0.028 one
      sided) of CHD incidence, while the original HHS result was a 34% reduction
      (P=0.008 one sided). However, when comparing Kaplan-Meier plots of cumulative
      hazards of CHD, the plot with a wider definition of CHD (ICD-8 and ICD-9 codes
      410-414) came closest to the HHS experience, especially if revascularizations
      were included in the latter. Definite AMI as a single definition of CHD might
      thus not be sufficient when studying CHD risk, instead, at least two parallel
      definitions of CHD should be used.

PMID- 9240632
TI  - Predictive value of potential doubling time in head and neck cancer patients
      treated by conventional radiotherapy.
AB  - PURPOSE: The goal of this study was to investigate the clinical utility of
      pretreatment measurements of tumor cell kinetics to predict the outcome of
      patients with squamous cell carcinoma of the head and neck receiving conventional
      radiotherapy. METHODS AND MATERIALS: All patients received between 64 and 70 Gy
      as 2 Gy fractions, five fractions per week. Cell kinetics were assayed rapidly
      and quantitatively using flow cytometric evaluation of iododeoxyuridine (IdUrd)
      incorporation, in vivo, from a biopsy removed several hours after the
      administration of the DNA precursor to the patient prior to the start of
      treatment. RESULTS: The measured proliferation parameters were not related to the
      clinicopathological features of the tumors, emphasizing the independent nature of
      these parameters. In univariate analysis, nodal involvement was the most
      important clinical feature of the tumors related to local control followed by
      Tpot, DNA aneuploidy, and attainment of complete regression at 6 weeks. Of these
      only Tpot and nodal status maintained significance in multivariate analysis, with
      respect to loco-regional control. In subgroup analysis, Tpot was able to stratify
      patients into high or low rate of loco-regional control in node negative
      patients, in aneuploid tumors and in patients who did achieve complete regression
      at 6 weeks. For cause specific survival, N-stage was the only parameter that
      significantly discriminated the prognosis in these patients. CONCLUSIONS: The
      conclusion of this study is that Tpot provides clinically important information
      that can predict patients with a low probability of achieving long-term local
      control with conventional fractionation. Further improvements to the methodology
      to address the shortcomings of analyzing diploid tumors may increase the
      predictive power of the measurement.

PMID- 9240633
TI  - Feasibility and outcome of a progressively accelerated concomitant boost
      radiotherapy schedule for head and neck carcinomas.
AB  - PURPOSE: To evaluate toxicity and treatment outcome in patients with head and
      neck carcinomas treated with a modified bifractionated concomitant boost
      radiotherapy schedule. METHODS AND MATERIALS: Eighty-five patients were treated
      from February 1991 to October 1995. According to clinical TN stage 23 tumors were
      T1, 33 T2, 20 T3, 9 T4, 44 N0, and 41 N1-N3. The primary tumor was located in the
      oral cavity in 6 patients, oropharynx in 36, larynx in 19, hypopharynx in 17, and
      nasopharynx in 7. The basic treatment delivered 50.4 Gy in 28 fractions, once a
      day, to the primary site and both sides of the neck. During the last 3.5 weeks, a
      boost to the initial gross disease was delivered in 13 fractions of 1.5 Gy each
      as a second daily fraction in a progressively accelerated schedule (total dose
      69.9 Gy). Eighteen patients had a uni- or bilateral neck dissection, and 2 an
      adenectomy before radiotherapy. The median follow-up for the surviving patients
      was 28 months (range: 3-61 months). RESULTS: All the patients completed the
      planned radiotherapy schedule. According to the RTOG scoring system, 57 patients
      (67%) presented with Grade 3-4 acute toxicity. Grade 3 dysphagia was observed in
      20 patients (23.5%). Three patients died during the 3 months following the
      treatment. Among 73 patients evaluable for late effects, five developed Grade 3-4
      complications. At 3 years actuarial loco-regional control was 67% and overall
      survival was 62%. CONCLUSIONS: Although longer follow-up is needed to evaluate
      the definitive results, we conclude that this particular concomitant boost
      schedule is feasible and appears to be effective. While acute toxicity was
      greater than in monofractionated schedules, it was manageable, provided that
      supportive care measures were implemented in a timely fashion.

PMID- 9240635
TI  - Low energy Helium-Neon laser in the prevention of oral mucositis in patients
      undergoing bone marrow transplant: results of a double blind randomized trial.
AB  - PURPOSE: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the
      prevention of oral mucositis induced by high dose chemoradiotherapy before
      autologous bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1993
      and 1995, 30 consecutive patients receiving an autologous peripheral stem-cell or
      bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to
      possibly receive prophylactic laser to the oral mucosa after giving informed
      consent. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously
      (I.V.) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg I.V. on d-4 in
      three cases. Total body irradiation (TBI) consisted of 12 Gy midplane dose in six
      fractions (4 Gy/day for three days). He-Ne laser (632.8 nm wavelength, power 60
      mW) applications were performed daily from d-5 to d-1 on five anatomic sites of
      the oral mucosa. Oral examination was performed daily from d0 to d + 20.
      Mucositis was scored according to an oral exam guide with a 16 item scale of
      which four were assessed by the patients themselves. Mean daily self assessment
      scores for oral pain, ability to swallow and oral dryness were measured. A daily
      mucositis index (DMI) and a cumulative oral mucositis score (COMS) were
      established. Requirement for narcotics and parenteral nutrition was recorded.
      RESULTS: The COMS was significantly reduced among laser treated (L+) patients (p
      = 0.04). The improvement of DMI in L+ patients was also statistically significant
      (p < 0.05) from d + 2 to d + 7. Occurrence and duration of grade III oral
      mucositis were reduced in L+ patients (p = 0.01). Laser applications reduced oral
      pain as assessed by patients (p = 0.05) and L+ patients required less morphine (p
      = 0.05). Xerostomia and ability to swallow were improved among the L+ patients (p
      = 0.005 and p = 0.01, respectively). Requirement for parenteral nutrition was not
      reduced (p = NS). CONCLUSION: Helium-Neon laser treatment was well tolerated,
      feasible in all cases, and reduced high dose chemoradiotherapy-induced oral
      mucositis. Optimal laser treatment schedules still needs to be defined.

PMID- 9240634
TI  - Radiotherapy and concomitant weekly 1-hour infusion of paclitaxel in the
      treatment of head and neck cancer--results from a Phase I trial.
AB  - PURPOSE: To define the maximum tolerated dose (MTD) by describing the dose
      limiting toxicity (DLT) of weekly paclitaxel (PAC) given as a 1-h I.V. infusion
      in patients with head and neck cancer concomitant to irradiation. METHODS AND
      MATERIALS: Patients with unresectable or incompletely resected head and neck
      cancer were enrolled into a prospective, dose-escalating Phase I study. Toxicity
      was graded according to the WHO toxicity score. MTD dose was defined when two out
      of six patients developed DLT. The starting dose of PAC was 20 mg/m2 once weekly
      I.V. over 60 min, with a subsequent dose escalation of 10 mg/m2 in cohorts of
      three new patients. Radiation therapy was administered in three field technique
      over 6-7 weeks in 2.0 Gy/daily fractions for 5 consecutive days/week up to total
      doses of 60-70 Gy. RESULTS: From 1994-1996, 18 patients completing three dose
      levels were included into the study. Altogether, 101 courses of chemotherapy were
      evaluable for toxicity. On the second dose level (30 mg/m2) one of three patients
      experienced DLT with Grade IV mucositis. On the next dose level with 40 mg/m2 PAC
      weekly one patient experienced DLT being prolonged Grade III mucositis. From the
      following three patients required, two patients showed no DLT. The third patient
      showed mucositis of WHO Grade 4 and died from hemorrhage caused by a rupture of
      the a pharyngeal wall. Dose level 2 (30 mg/m2) was repeated and one of the three
      newly treated patients again suffered from mucositis WHO Grade 4. CONCLUSION:
      When PAC is given weekly as a 1-h infusion concomitant to radiotherapy, MTD is 30
      mg/m2 with mucositis being DLT; hematological and further nonhematological
      toxicity is mild.

PMID- 9240636
TI  - Reduction of radiation-induced xerostomia in nasopharyngeal carcinoma using CT
      simulation with laser patient marking and three-field irradiation technique.
AB  - PURPOSE: Tumor control and reduction of postirradiation xerostomia in patients
      with nasopharyngeal carcinoma (NPC) using the three-field irradiation technique
      based on the CT-based simulation with laser patient marking was investigated.
      METHODS AND MATERIALS: Seventy-eight patients with NPC were consecutively treated
      between 1983 and 1993. In 33 patients treated before 1987, target volume was
      determined using a conventional x-ray simulator with a reference of CT images,
      and the primary site was treated by the conventional parallel-opposed two-field
      technique (Group I). In 45 patients treated from 1987, target volume was
      determined using a CT simulator slice by slice, the treatment field was projected
      onto the patient's skin by a laser beam projector mounted on a C-arm, and the
      primary site was irradiated by a three-fields (anterior and bilateral) technique
      (Group II). In Group II, the shape of each field was determined using a beam's
      eye view to reduce the dose to the bilateral parotid glands. The three-field
      technique reduced the dose to the superficial lobe of parotid gland to about two
      thirds of the dose given by the two-field technique. Radiation-induced xerostomia
      was evaluated by clinical symptoms and radioisotope sialography. RESULTS: The 5
      year survival rate and disease-free survival rate were 46.6 and 31.2% in Group I,
      and 46.8 and 46.5% in Group II. A large variation in the volume of parotid glands
      were demonstrated, ranging from 9 cm3 to 61 cm3 among patients treated with CT
      simulation. Forty percent of the patients in Group II showed no or mild
      xerostomia, whereas all of the patients in Group I showed moderate to severe
      xerostomia (p < 0.01). The radioisotope sialography study showed that the mean
      secretion ratio by acid stimulation was improved from 3.8% in the Group I to
      15.2% in the Group II (p < 0.01). CONCLUSIONS: CT simulation was useful to
      determine the size and shape of each field to reduce the dose to the parotid
      gland, of which size varies largely among individual patients. The three-field
      technique based on CT simulation with laser patient markings is suggested to
      result in superior complication-free survival in terms of salivary dysfunction
      than did the conventional two-field technique with x-ray simulatior for NPC.

PMID- 9240637
TI  - Treatment results and prognostic factors in 101 men treated for squamous
      carcinoma of the penis.
AB  - PURPOSE: This retrospective study was performed to assess the treatment outcome
      and prognostic factors in 101 men with invasive squamous carcinoma of the penis
      treated at the Royal Marsden Hospital between 1960-1990. METHODS AND MATERIALS:
      The tumor was confined to the glans penis (T1) in 79 patients, 82 were node
      negative (N0), and two patients had distant metastases at presentation. The
      histology was Grade 1 (G1) in 36, Grade 2 (G2) in 18, Grade 3 (G3) in 28, and
      unknown in 19 patients. Node-positive disease was commoner in patients with G3 (p
      = 0.02) or T2/3/4 tumors (p = 0.007). Treatment for the primary tumor was
      external beam radiotherapy (EBRT) in 59, interstitial brachytherapy in 13, and
      partial or total penectomy in 29 patients. The median dose, dose/fraction, and
      treatment time for EBRT was 60 Gy, 2 Gy/fraction, and 46 days, respectively.
      Eighty patients received no inguinal node treatment, 13 had EBRT (4 with
      chemotherapy), and 8 underwent groin dissection at presentation. RESULTS: During
      a median follow-up of 5.2 years (2 months-22 years), 56 patients died (penile
      cancer 31, intercurrent illness 23 and unknown cause 2), giving 10 year overall
      and cause-specific survival (CSS) of 39 and 57%, respectively. Adverse prognostic
      factors for CSS on univariate analysis were G3, ulcerative/fungating or T2/3/ 4
      tumors, node positive, Jackson's Stage 2/3/4, and surgical treatment for the
      primary. All but the last two were significant independent prognostic factors for
      CSS on multivariate analysis. Penile or perineal recurrence or residual disease
      after initial treatment was seen in 36 out of 98 evaluable patients, giving a 10
      year local failure rate (LFR) of 45%. Local failure after initial treatment was
      successfully salvaged in the majority (26 out of 36) of patients with further
      surgery or radiotherapy, and local control was achieved ultimately in 74 out of
      77 T1, 7 out of 12 T2; 3 out of 3 T3, and 3 out of 5 T4 tumors. In the 44
      evaluable patients with T1 tumors treated by EBRT the only adverse RT parameter
      approaching prognostic significance (p = 0.052) was a BED value corrected for
      recovery of <60 Gy (alpha/beta 10, K = 0.5 Gy/day, mean = 21 days). CONCLUSION:
      Invasive squamous carcinomas of the penis carry a significant risk of loco
      regional recurrence after initial radiotherapy and this can be successfully
      salvaged in most patients with further treatment. This mandates close follow-up
      to detect loco regional recurrence early.

PMID- 9240638
TI  - Stage T1-2 prostate cancer with pretreatment prostate-specific antigen level < or
      = 10 ng/ml: radiation therapy or surgery?
AB  - PURPOSE: To detect differences in biochemical failure rates by treatment modality
      (radiation therapy or radical prostatectomy) in patients with early-stage
      prostate cancer presenting with pretreatment prostatic-specific antigen (PSA)
      levels < or = 10.0 ng/ml. METHODS AND MATERIALS: A total of 1467 consecutive
      patients with prostate carcinoma were treated with either radiotherapy (RT) or
      radical prostatectomy (RP) between January 1987 and June 1996. Patients with the
      following were excluded from the present study: initial PSA (iPSA) level > 10
      ng/ml (n = 444), clinical Stage T3 disease (n = 73), adjuvant or neoadjuvant
      treatment (n = 173), no available iPSA level (n = 31), no available biopsy
      Gleason score (GS) (n = 33), incomplete pathologic information (n = 16), and no
      available follow-up PSA levels (n = 90). The analysis was performed on 607 cases:
      354 treated with RP and 253 with RT (median dose 68.4 Gy). The outcome of
      interest was biochemical relapse-free survival (bRFS), with biochemical relapse
      being defined as either a detectable PSA level after RP or elevation in PSA
      levels of > or = 1.0 ng/ml above the nadir after RT. Proportional hazards were
      used to analyze the effect of treatment modality and confounding variables (i.e.,
      age, stage, biopsy GS, iPSA levels) on treatment outcome. RESULTS: Seventy-nine
      percent of patients (n = 478) had clinical Stage T1 or T2A disease at
      presentation (RP vs. RT: 84% vs. 71%, p < 0.001). Twenty-one percent of patients
      (n = 127) had iPSA levels < or = 4 ng/ml (RP vs. RT: 24% vs. 17%, p = 0.027).
      Seventy-six percent of patients (n = 460) had biopsy GS < or = 6 (RP vs. RT: 79%
      vs. 71%, p = 0.014). The median follow-up time was 24 months (range 3-110). For
      the 607 patients, the 5-year bRFS rate was 76%. The 5-year RFS rates for RP
      versus RT were 76% versus 75%, respectively (p = 0.09). After adjustment for all
      confounding variables, iPSA levels (p < 0.001) and biopsy GS (p = 0.001) were the
      only independent predictors of relapse, whereas age, clinical stage, and
      treatment modality were not (p = 0.20; p = 0.09; and p = 0.10, respectively).
      CONCLUSION: In patients with clinical Stage T1-2 prostate cancer and pretreatment
      PSA < or = 10 ng/ml, there is no difference in biochemical failure rates between
      those treated with radiation and those treated with surgery.

PMID- 9240639
TI  - Adjuvant and salvage irradiation following radical prostatectomy for prostate
      cancer.
AB  - PURPOSE: We performed a retrospective analysis to assess the durability of
      benefit derived from irradiation after prostatectomy for pT3N0 disease, and the
      possibility of cure. METHODS AND MATERIALS: We studied 88 patients who were
      irradiated after prostatectomy and had available prostate specific antigen (PSA)
      data, no known nodal or metastatic disease, no hormonal treatment, and follow-up
      of at least 12 months from surgery. Forty patients received adjuvant therapy for
      a high risk of local failure with undetectable PSA. Forty-eight patients received
      salvage therapy for elevated PSA levels. Mean follow up was 44 months from date
      of surgery and 31 months from irradiation. Biochemical failure was strictly
      defined as a confirmed rise in PSA of >10%, or as the ability to detect a
      previously undetectable PSA value. RESULTS: After salvage irradiation, 69% of
      patients attained an undetectable PSA. Eighty-eight percent of adjuvant patients
      were biochemically and clinically free of disease (bNED) at 3 years from
      prostatectomy. Sixty-eight percent of those receiving salvage irradiation were
      bNED 3 years after surgery. On univariate analysis, treatment group (adjuvant or
      salvage), pre-operative PSA, and the status of seminal vesicles were significant
      prognostic factors. The extent of PSA elevation in the salvage group was also
      significant. We did not demonstrate a significant difference between those
      salvage patients referred for persistently elevated PSA as compared to those with
      a late rise in PSA. On multivariate analysis, the only significant predictor of
      outcome was treatment group, with adjuvant irradiation having better outcome than
      salvage. CONCLUSION: More than two-thirds of this group of patients remain
      biochemically disease free at 3 years following irradiation, attesting to a
      number of potential cures. For patients with stage pT3N0 prostate cancer
      following radical prostatectomy, our data support the use of either routine
      postoperative adjuvant irradiation or close PSA follow-up with early salvage
      treatment.

PMID- 9240640
TI  - Localization of the prostatic apex for radiotherapy treatment planning using
      urethroscopy.
AB  - PURPOSE: To assess the ability of computed tomography (CT) scans and retrograde
      urethrograms to accurately define the prostatic apex in the craniocaudad
      dimension, using urethroscopy as a reference. METHODS AND MATERIALS: Plain film
      radiographs of the pelvis were obtained in 15 patients with early-stage
      adenocarcinoma of the prostate, with the tip of a urethroscope held in place at
      the external sphincter, which most closely approximates the prostatic apex. The
      scope was then withdrawn, and a retrograde urethrogram was performed. Immediately
      afterwards, a CT scan of the pelvis was obtained. Because differential filling of
      the bladder and rectum affects the position of the prostatic apex, patients
      voided prior to rather than in between the three consecutive studies. RESULTS:
      The urethroscopy-defined prostatic apex was located 4 +/- 8 mm (mean +/- SD)
      superior to the CT-defined apex, 13 +/- 3 mm (mean +/- SD) superior to the
      urethrogram tip and 30 +/- 7 mm (mean +/- SD) superior to the ischial
      tuberosities. There was significant interobserver variability in the location of
      the prostatic apex as determined by CT scans. Placement of the inferior border of
      the radiation portals at the ischial tuberosities would have resulted in
      irradiation of > or = 20 mm bulbar urethra, as defined by the dye column of the
      retrograde urethrogram, in 6 out of 15 (40%) of the patients and irradiation of <
      10 mm bulbar urethra in 2 out of 15 (13%) of the patients. CONCLUSION: Because
      the prostate blends inferiorly with the urogenital diaphragm, CT scans do not
      allow one to precisely localize the prostatic apex. Due to anatomic variability,
      the ischial tuberosities do not allow one to accurately localize the prostatic
      apex. Retrograde urethrograms provide helpful supplemental information regarding
      the position of the prostatic apex for radiotherapy treatment planning.

PMID- 9240641
TI  - A feasibility study of high dose rate brachytherapy in solitary urinary bladder
      cancer.
AB  - PURPOSE: To determine the feasibility of high dose rate brachytherapy in the
      treatment of T1-T3 solitary bladder cancer and to compare results and side
      effects to those obtained by others using conventional, i.e., low dose rate
      regimens. METHODS AND MATERIALS: Between July 1992 and 1995, 16 patients entered
      the study. Median age at diagnosis was 64 years (range: 45-79 years). Diagnostic
      transurethral resection showed four T1, five T2, and seven T3 lesions, all proven
      solitary by random biopsies. Radiotherapy consisted of low-dose preoperative
      external beam irradiation (3 x 3.5 Gy on the 3 consecutive days prior to
      implantation), followed by high dose rate brachytherapy (15 x 3 Gy during the 8
      consecutive days thereafter). Median follow-up from the date of implantation was
      23 months (range: 6-43 months). In 15 patients, cystoscopy was systematically
      performed during follow-up, whereas the 16th patient was followed on a clinical
      basis only. RESULTS: Recurrences have occurred in 2 of 15 evaluable patients
      (both stage T3): metastasis in 1 and combined local plus distant failure in the
      other patient. Cystoscopic evaluation showed persisting alterations of the
      implanted portion of the bladder mucosa in 11 of 15 evaluable patients
      (ulceration, calcifications, and/or punctiform bleedings). Symptomatic radiation
      cystitis was mild and transient in 14 but persisting and severe in 2 patients.
      CONCLUSION: This study documents the feasibility of high dose rate brachytherapy
      in a selected group of bladder cancer patients. Both patient outcome and side
      effects are comparable to the best results obtained with low dose rate schedules.
      Additional follow-up is still needed to enforce the comparison.

PMID- 9240642
TI  - Does T1, N0-1 vulvar cancer treated by vulvectomy but not lymphadenectomy need
      inguinofemoral radiation?
AB  - PURPOSE: The objective of our study was to demonstrate differences in relapse
      rates, total survival times, and complication rates between inguinofemoral
      radiation and its absence in cases of invasive vulvar carcinoma without lymph
      node involvement (FIGO Stages T1, N0-1). METHODS AND MATERIALS: From 1974 to
      1990, 135 patients with invasive vulvar carcinoma in Stage T1 without clinical
      evidence of inguinal lymph node involvement underwent simple vulvectomy performed
      by hot-knife resection without lymphadenectomy. Although 65 patients (Group 1)
      received postoperative inguinofemoral radiation therapy, 70 patients (Group 2)
      did not, and none received local vulva irradiation. RESULTS: The 5-year survival
      rates were 93.7% in Group 1 and 91.4% in Group 2 (p = NS). Although clitoris
      involvement was significantly more prevalent in the irradiation group (p = 0.04),
      inguinal relapse was found less frequently in Group 1 (4.6% or 3 out of 65
      patients) than in group 2 (10% or 7 out of 70 patients) (p = 0.32). The
      complication rates were, 7.7% in Group 1 and 2.9% in Group 2, 2.7% for vaginal
      stenosis (two patients in each group), 1.5% for inguinal pain (one patient in
      Group 1), 1.5% for rectovaginal fistula (one patient in Group 1), 1.5% for vulvar
      infection (one patient in Group 1). CONCLUSION: No statistically significant
      differences in the relapse rates and survival times were found. Risk factors were
      equally distributed in both study groups except for clitoris involvement. The 5
      year survival rates in both groups were similar to those reported in the
      literature for radical vulvectomy and inguinal lymph-node dissection (83-96%).
      Morbidity in our study was low. Although our data showed similar results in both
      groups, we are not recommending at this time to omit groin radiation in general,
      but it may be justified in low-risk cases.

PMID- 9240643
TI  - The use of ultrasonography in the localization of the lumpectomy cavity for
      interstitial brachytherapy of the breast.
AB  - PURPOSE: To determine the value of breast ultrasonography (US) in defining the
      lumpectomy cavity for patients treated with interstitial brachytherapy. METHODS
      AND MATERIALS: In March 1993, a protocol of low dose rate (LDR) interstitial
      brachytherapy as the sole radiation modality in selected patients with early
      breast cancer was initiated at William Beaumont Hospital. To date, 60 patients
      have been entered in this protocol, and 38 have undergone US assisted placement
      of interstitial brachytherapy needles. The lumpectomy cavity was outlined in all
      dimensions and corresponding skin marks were placed for reference at time of
      implantation. These US dimensions were compared to the physician's clinical
      estimate of the location of the lumpectomy cavity, the patient's presurgical
      mammogram, and the position of the surgical scar. In the intraoperative setting,
      the dimensions of the lumpectomy cavity were also obtained and the placement of
      the deep plane of interstitial needles was verified by US. RESULTS: The full
      extent of the lumpectomy cavity was underestimated by clinical examination
      (physical exam, operative report, mammographic information and location of the
      surgical scar) in 33 of 38 patients (87%). The depth to the chest wall was also
      incorrectly estimated in 34 (90%) patients when compared to US examination.
      Intraoperatively, US was performed in nine patients and was useful in verifying
      the accurate placement of the deepest plane of interstitial brachytherapy
      needles. In 7 of 9 patients (75%), clinical placement of needles did not ensure
      adequate coverage of the posterior extent of the lumpectomy cavity as visualized
      by intraoperative US. CONCLUSIONS: In breast cancer patients considered for
      interstitial brachytherapy, US appears to be a more accurate means of identifying
      the full extent of the lumpectomy cavity when compared to clinical estimates. In
      addition, US allows real-time verification of needle placement in the
      intraoperative setting.

PMID- 9240644
TI  - Results of breast conserving therapy for early breast cancer and the role of
      mammographic follow-up.
AB  - PURPOSE: The following article is a review of 23 years of breast-conserving
      therapy in our hospital. This study was performed to assess and improve the
      follow-up care of women with early breast cancer and to evaluate whether or not
      biannual mammogram is useful. METHODS AND MATERIALS: Between 1972 and December
      1995, 3072 women with pathological size pT1 and pT2 breast cancer were treated
      with conservative surgery and radiation therapy. Eighty-five patients developed a
      recurrence in the treated breast as the first site of failure, 12 of which had
      positive axillary nodes. In the following patient study, those with an
      noninvasive recurrence were excluded. A retrospective assessment of the entire
      mammographic course was made, starting with the mammogram at the time of original
      diagnosis to the mammogram of the recurrence. RESULTS: In our study group the
      probability for local failure ranged from 1 to 2% per year. At 5 and 10 years the
      actuarial rates were 5 and 10%. The median time to recurrence was 41 months
      (range 8-161). Twenty-six (31%) recurrences were detected by mammography alone,
      10 (12%) by clinical examination only, and 35 (41%) by both methods. For the
      patients with an ipsilateral recurrence, the overall actuarial 5- and 10-year
      survival after treatment was 87 and 70%, respectively. The 5-year actuarial rate
      of survival from salvage mastectomy was 61%. CONCLUSION: Considering the high
      percentage of recurrences detectable by mammography and the possibility of
      detection within a short-term interval, we think biannual mammographic follow-up
      is appropriate for the first years following breast-conserving therapy.

PMID- 9240645
TI  - Radiotherapy with high dose rate brachytherapy boost and concomitant chemotherapy
      for Stages IIB and III esophageal carcinoma: results of a pilot study.
AB  - PURPOSE: Radiotherapy (RT) and concomitant chemotherapy (CT) is the standard
      treatment for non resectable esophageal cancer. Usual total radiation dose is 50
      Gy. In order to enhance local control rate a Phase II study was initiated to
      evaluate the feasibility of a combined treatment with an external radiation dose
      of 60 Gy and three cycles of concomitant CT, using the three main active drugs
      (CDDP, 5 FU and MMC), followed by a high dose rate (HDR) brachytherapy delivering
      10 Gy. METHODS AND MATERIALS: Fifty-three patients, 48 men and 5 women, were
      entered in this study. Stages were evaluated with CT scan and with endoscopic
      sonography. Fifteen were Stage IIB, 38 Stage III. Treatment consisted of
      conventional fractionated RT to a total dose of 60 Gy delivered with 2 Gy per
      fraction, one fraction per day and five fractions per week. The CT regimen was a
      combination of Cisplatinum (CDDP) 20 mg/m2 and 5 Fluorouracil (5FU) 600 mg/m2
      continuous infusion, from days 1-4 Mitomycin C (MMC) was given at 6 mg/m2 on day
      1. Three cycles were administered on days 1, 22, and 43. Brachytherapy was
      delivered one week after the end of external radiation therapy. RESULTS: Full
      radiation therapy dose was delivered for 94% of the patients. CT compliance,
      evaluated on the mean relative dose-intensity was 85% for CDDP, 81% for 5FU and
      51% for MMC. Overall grade 3 and 4 WHO toxicity rates were 23% and 7%,
      respectively. Haematologic toxicity was the most limiting factor. One patient
      died from treatment toxicity. Local control rate at one year was 74%. Three-year
      actuarial survival rate was 27%. Distant metastasis was the main cause of
      treatment failure. Swallowing score was good for 75% of the patients. Stage,
      performance status and weight loss were prognostic factors. CONCLUSION: This
      regimen with high dose RT, HDR brachytherapy and concomitant CT is feasible;
      however, a high level of haematologic toxicity was observed with the CDDP, 5FU
      and MMC regimen. Despite a poor compliance with CT, treatment results are very
      encouraging for patients with locally advanced disease.

PMID- 9240646
TI  - Locally advanced rectal carcinoma: pelvic control and morbidity following
      preoperative radiation therapy, resection, and intraoperative radiation therapy.
AB  - PURPOSE: To determine the impact of intraoperative radiation therapy (IORT)
      combined with preoperative external beam irradiation and surgical resection in
      patients with locally advanced, unresectable rectal carcinoma. METHODS AND
      MATERIALS: Between 1982 and 1993, 40 patients with locally advanced colorectal
      cancer unresectable at initial presentation were treated with preoperative
      external beam radiation therapy (median dose 50.4 Gy). Thirty patients received
      concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had
      recurrent disease; 1 patient had a solitary hepatic metastasis at the time of
      surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and
      if microscopic or gross residual disease was encountered, IORT was delivered to
      the tumor bed. Patients with an unevaluable or high-risk margin were also
      considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage
      unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically
      prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5
      100). RESULTS: Thirty-three patients were able to undergo a curative resection
      (83%). Five patients had gross residual disease despite aggressive surgery. Seven
      patients did not receive IORT: six because of clear margins, and one with gross
      disease that could not be treated for technical reasons. The remainder of the
      patients (26) received IORT to the site of pelvic adherence. The crude local
      control rates for patients following complete resection with negative margins
      were 92% for patients treated with IORT and 33% for patients without IORT. IORT
      was ineffective for gross residual disease. Pelvic control was none of four in
      this setting. The crude local control rate of patients with primary cancer was
      73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The
      5-year actuarial overall survival and local control rates for patients undergoing
      gross complete resection and IORT were 64% and 75%, respectively. Seventeen of
      the 26 patients (65%) who received IORT experienced pelvic complications, as
      opposed to two patients (28%) who did not receive IORT. The incidence of
      complications was similar in the patients with primary versus recurrent disease.
      All cases were successfully treated with the placement of a posterior thigh
      myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series.
      CONCLUSION: Patients with locally advanced carcinoma of the rectum were
      aggressively treated with combined modality therapy consisting of preoperative
      external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82%
      for patients with minimal residual disease. IORT failed to control gross residual
      disease. The incidence of pelvic wound healing problems was 65% in this series;
      however, a reconstructive procedure which replaced irradiated tissue with a
      vascularized myocutaneous flap was successful in treating this complication. We
      believe that IORT has therapeutic merit in the treatment of locally advanced
      rectal cancer, particularly in the setting of minimal residual disease.

PMID- 9240647
TI  - Palliative reirradiation for recurrent rectal cancer.
AB  - PURPOSE: The purpose of this study was to analyze the efficacy and acute and late
      toxicity of reirradiation for recurrent rectal cancer. METHODS AND MATERIALS:
      Fifty-two patients with recurrent rectal adenocarcinoma following previous pelvic
      RT underwent reirradiation. Median initial RT dose to the pelvis was 50.4 Gy.
      Median reirradiation dose was 30.6 Gy. Twenty-two patients received 1.2 Gy
      b.i.d., and 30 patients received 1.8-2.0 Gy daily. Total cumulative doses ranged
      from 66.6 to 104.9 Gy (median: 84.4 Gy). Forty-seven patients (90%) received
      concurrent 5-FU chemotherapy. Forty-four patients were followed until death, and
      the median follow-up time was 16 months. RESULTS: The RTOG Grade 3 acute toxicity
      rate was 31%. The RTOG Grade 3 and 4 late toxicity rates were 23 and 10%,
      respectively. On multivariate analysis, the only factor associated with reduced
      late toxicity was hyperfractionated delivery of reirradiation. Bleeding, pain,
      and mass effect were palliated completely in 100, 65, and 24% of instances,
      respectively, and the majority of responding patients were palliated until death.
      The overall median survival time from retreatment was 12 months. The 2- and 3
      year overall actuarial survival rates were 25 and 14%, respectively. CONCLUSION:
      This unique institutional approach to recurrent rectal cancers resulted in
      excellent palliation of symptoms. Late complications appeared reduced by
      hyperfractionated treatment delivery.

PMID- 9240648
TI  - Comparison of two repositioning devices used during radiation therapy for
      Hodgkin's disease.
AB  - PURPOSE: Patients irradiated for Hodgkin's disease are fixed in an immobilization
      cradle to improve repositioning. In the early 1990s, we changed our cradle system
      from a "short" upper torso cradle to an extended near-total body cradle that also
      includes the lower torso and thighs. In this study, we assess the impact of the
      extended cradle on the reproducibility of patient repositioning during
      irradiation of Hodgkin's disease. METHODS AND MATERIALS: A total of 782 port
      films of 56 patients treated immediately before and after the change-over were
      studied to assess positioning reproducibility. Patients treated prior to 1993
      were positioned in the short cradle, while those treated 1993 and later were
      positioned in the extended cradle. All treatment were delivered via anterior and
      posterior fields and treatment areas above and below the diaphragm were
      considered separately and together. All treatment fields were simulated and the
      field shape was designed on anterior and posterior radiographs. Discrepancies in
      field placement between the simulation radiographs and subsequent port films were
      noted by a radiation oncologist and requests for position adjustment (both
      translational and rotational shifts) were noted. The number, magnitude, and
      direction of any physician-requested position adjustment on port films were
      retrospectively reviewed. For the purpose of scoring the frequency of field
      misplacements, when an adjustment was noted on two port films taken during the
      same treatment session (i.e., a left shift on both an anterior and a posterior
      port film), it was scored as only one event. A two-tailed chi-square test was
      used to compare the differences in requested shifts in the two patient groups.
      RESULTS: The study population consisted of 56 patients (31 short and 25 extended
      cradle) representing 92 treatment sites. A total of 782 port films representing
      450 treatment setups were analyzed (292 above and 158 below the diaphragm). When
      all port films above the diaphragm (mostly mantle fields) are considered,
      position adjustments were requested in 13.4% (21 out of 157) of treatment setups
      with the upper torso cradle and in 5.9% (8 out of 135) of treatment setups with
      the extended cradle (p = 0.054). When all port films below the diaphragm (mostly
      paraaortic/spleen and pelvic fields) are considered, position adjustments were
      requested in 33.8% (27 out of 80) of treatment setups with the upper torso cradle
      and in 16.7 % (13 out of 78) of treatment setups with the extended cradle (p =
      0.056). A reduction in the frequency of both translational and rotational
      adjustments were seen. When both treatment sites are combined, position
      adjustments were requested in 20.3% (48 out of 237) of treatment setups with the
      upper torso cradle and in 9.9% (21 out of 213) of treatment setups when the
      extended cradle was used (p = 0.0086). CONCLUSIONS: The extended cradle provides
      superior repositioning of patients undergoing radiation therapy for Hodgkin's
      disease. Differences observed in setup accuracy in this study underscore the
      importance of aggressive immobilization of patients with Hodgkin's disease.
      Increased accuracy of daily setup may provide an opportunity to improve the
      therapeutic ratio both by increased likelihood of tumor control and decreased
      risk of normal tissue complications.

PMID- 9240649
TI  - Radiation therapy for rhabdomyosarcoma: local failure risk for Clinical Group III
      patients on Intergroup Rhabdomyosarcoma Study II.
AB  - PURPOSE: A subset of 362 pediatric patients with rhabdomyosarcoma was selected
      from a total of 532 eligible IRS-II patients in Clinical Group III to assess the
      local and regional failure rates following radiotherapy and to determine patient,
      tumor, and treatment factors contributing to the risk for local and regional
      failure. METHODS AND MATERIALS: The study population was selected from all
      eligible IRS-II Clinical Group III patients. Excluded patients were those with
      "special pelvic" primary sites whose protocol management restricted radiotherapy
      (n = 123), and those who were removed from the study before radiotherapy was to
      begin, or because it was omitted (n = 47). A binary recursive partitioning model
      was used to identify subgroups of the remaining 362 patients at risk of local or
      regional failure. RESULTS: The local (only) failure rate was 17% (95% confidence
      interval, 13-21%), and the local (all) failure rate was 20% (95% confidence
      interval, 16-24%). The 5-year actuarial risk of local (all) failure was 22% (95%
      confidence interval, 18-27%). The risk of regional (nodal) failure was between 2%
      and 23%. Increasing tumor size predicted an increased local failure risk. Primary
      tumors located above the clavicle had a reduced risk of local failure. The binary
      recursive partitioning model identified a subset of patients at high risk of
      local failure. Those patients had primary tumors in the chest, pelvic region,
      extremity, or trunk, or tumors > 10 cm in diameter. Their local failure rate was
      35% (compared to 15% for the remaining patients). The subset of patients at high
      risk for regional (nodal) failure had node involvement at diagnosis and a primary
      tumor originating at a site other than orbit, parameningeal, or trunk. Compliance
      with radiation treatment guidelines approached but did not achieve statistical
      significance as a predictive factor for local failure. By univariate analysis,
      factors not influencing local failure risk were age, race, gender, adenopathy,
      and histology. CONCLUSION: Radiation therapy and chemotherapy administered to
      Clinical Group III patients entered into the IRS-II protocol produced sustained
      local control in most cases. Knowledge of the factors which predict an increased
      risk of local or regional failure will facilitate the design of new treatment
      strategies.

PMID- 9240650
TI  - Potential role of proton therapy in the treatment of pediatric
      medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation.
AB  - PURPOSE: Conventional postoperative photon-beam radiotherapy to the spine in
      children with medulloblastoma/PNET is associated with severe late effects. This
      morbidity (growth and developmental) is related to the exit dose of the beams and
      is particularly severe in young children. With the purpose of reducing this
      toxicity, a dosimetric study was undertaken in which proton therapy was compared
      to standard megavoltage photon treatment. METHODS AND MATERIALS: The results of a
      comparative dosimetric study are presented in such a way that the dose
      distribution achievable with a posterior modulated 100 MeV proton beam (spot
      scanning method) is compared with that of a standard set of posterior 6 MV x-ray
      fields. The potential improvements with protons are evaluated, using dose-volume
      histograms to examine the coverage of the target as well as the dose to the
      vertebral bodies (growth plates), lungs, heart, and liver. RESULTS: The target
      (i.e., the spinal dural sac) received the full prescribed dose in both treatment
      plans. However, the proportions of the vertebral body volume receiving > or = 50%
      of the prescribed dose were 100 and 20% for 6 MV x-rays and protons,
      respectively. For 6 MV x-rays > 60% of the dose prescribed to the target was
      delivered to 44% of the heart volume, while the proton beam was able to
      completely avoid the heart, the liver, and in all likelihood the thyroid and
      gonads as well. CONCLUSION: The present study demonstrates a potential role of
      proton therapy in decreasing the dose (and toxicity) to the critical structures
      in the irradiation of the spinal neuraxis in medulloblastoma/PNET. The potential
      bone marrow and growth arrest sparing effects make this approach specially
      attractive for intensive chemotherapy protocols and for very young children.
      Sparing the thyroid gland, the posterior heart wall, and the gonads may be
      additional advantages in assuring a long-term posttreatment morbidity-free
      survival.

PMID- 9240651
TI  - Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3
      labeled with either 131I or 186Re in human ovarian cancer xenografts.
AB  - PURPOSE: The radionuclide 186Re has favorable physical characteristics for use in
      radioimmunotherapy, including the emission of beta-particles of a high-energy and
      a low-abundance of gamma-emission. The gamma-emission, in particular, is ideal
      for tumor imaging and poses less hazards to the patient and the medical personnel
      when compared with the gamma-emission of the widely used radionuclide 131I. In
      the present study, we determined whether 186Re-labeled monoclonal antibody 323/A3
      may be better suited for the treatment of ovarian cancer than 131I-323/A3.
      METHODS AND MATERIALS: We compared the biodistribution and the efficacy of 186Re-
      and 131I-labeled 323/A3 in nude mice bearing s.c. the human ovarian cancer
      xenografts FMa, OVCAR-3 and Ov.Pe. 186Re was conjugated to 323/A3 with the use of
      the S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) chelate. RESULTS: A molar
      ratio of Re-MAG3:323/A3 of 3:1 did not affect the integrity and the
      pharmacokinetic behaviour of the MAb. The tumor uptake and the retention of 186Re
      and 131I-labeled 323/A3 were comparable, but the cumulative absorbed radiation
      dose in the tumor delivered by 186Re-323/A3 was 1.3-fold higher than that of 131I
      323/A3. When mice were treated with equivalent radionuclide doses, the tumor
      growth inhibition induced by 186Re-323/A3 was similar or slightly better when
      compared with the efficacy of 131I-323/A3. When mice were treated with
      radionuclide doses that were adjusted to obtain equal cumulative absorbed
      radiation doses in the tumor for both conjugates, 131I-323/A3 was slightly more
      effective in the inhibition of the growth of FMa and OVCAR-3 xenografts.
      CONCLUSIONS: The favorable physical characteristics of 186Re as well as its
      efficacy when conjugated to a MAb indicate 186Re as an attractive radionuclide in
      radioimmunotherapy of ovarian cancer patients.

PMID- 9240652
TI  - Pulsed low dose rate brachytherapy in a rat model: dependence of late rectal
      injury on radiation pulse size.
AB  - PURPOSE: Clinical protocols utilizing pulsed low dose rate brachytherapy (PDR) to
      replace traditional continuous low dose rate brachytherapy (CLDR) employ
      irradiation in individual pulses given at intervals of a few hours. A critical
      factor in determining whether PDR will produce equivalent or greater late
      occurring normal tissue toxicity is the dose per pulse. A rat rectal model was
      used to determine the role of pulse size in modifying dose effectiveness in
      producing late-occurring toxicity. METHODS AND MATERIALS: A rat model in which
      the rectum is irradiated with 192Ir sources was used in conjunction with an
      intracavitary applicator. A section of rectum 1.3 cm in length was irradiated
      with either 0.75 Gy/h CLDR or one of five schemes of PDR. The schemes applied
      0.375, 0.75, 1.5, 3.0, or 6.0 Gy pulses at 0.5, 1.0, 2.0, 4.0, or 8.0 h
      intervals, respectively. Rats were observed for up to 300 days after completion
      of irradiation for rectal obstruction. Rectal specimens were taken at the time of
      sacrifice for obstruction or at the end of follow-up and analyzed histologically
      for injury. RESULTS: Effectiveness of irradiation was analyzed by calculating the
      ED50 for incidence of obstruction and severe histological injury. The ED50 for
      obstruction after treatment with CLDR and pulse sizes of 0.375, 0.75, and 1.5 Gy
      were 70.5, 68.0, 68.6, and 68.8 Gy, respectively. These values were not
      significantly different. Compared to CLDR, the ED50 for obstruction after pulse
      sizes of 3.0 and 6.0 Gy were significantly different at 60.9 and 46.3 Gy,
      respectively. The relative changes in ED50 for the different radiation schemes in
      producing ulceration, fibrosis, and vascular sclerosis injury were similar to
      that observed for obstruction. The endpoints of colitis cystica profunda and
      atypical epithelial regeneration varied less with increasing pulse size.
      CONCLUSIONS: We have demonstrated that for late rat rectal injury, dose responses
      to PDR pulse sizes up to 1.5 Gy at 2-h intervals are not distinguishable from
      that seen with CLDR at a dose rate of 0.75 Gy/h.

PMID- 9240653
TI  - Dosimetric comparison of treatment planning systems in irradiation of breast with
      tangential fields.
AB  - PURPOSE: The objectives of this study are: (1) to investigate the dosimetric
      differences of the different treatment planning systems (TPS) in breast
      irradiation with tangential fields, and (2) to study the effect of beam
      characteristics on dose distributions in tangential breast irradiation with 6 MV
      linear accelerators from different manufacturers. METHODS AND MATERIALS: Nine
      commercial and two university-based TPS are evaluated in this study. The computed
      tomographic scan of three representative patients, labeled as "small", "medium"
      and "large" based on their respective chest wall separations in the central axis
      plane (CAX) were used. For each patient, the tangential fields were set up in
      each TPS. The CAX distribution was optimized separately with lung correction, for
      each TPS based on the same set of optimization conditions. The isodose
      distributions in two other off-axis planes, one 6 cm cephalic and the other 6 cm
      caudal to the CAX plane were also computed. To investigate the effect of beam
      characteristics on dose distributions, a three-dimensional TPS was used to
      calculate the isodose distributions for three different linear accelerators, the
      Varian Clinac 6/100, the Siemens MD2 and the Philips SL/7 for the three patients.
      In addition, dose distributions obtained with 6 MV X-rays from two different
      accelerators, the Varian Clinac 6/100 and the Varian 2100C, were compared.
      RESULTS: For all TPS, the dose distributions in all three planes agreed
      qualitatively to within +/- 5% for the "small" and the "medium" patients. For the
      "large" patient, all TPS agreed to within +/- 4% on the CAX plane. The isodose
      distributions in the caudal plane differed by +/- 5% among all TPS. In the
      cephalic plane in which the patient separation is much larger than that in the
      CAX plane, six TPS correctly calculated the dose distribution showing a cold spot
      in the center of the breast contour. The other five TPS showed that the center of
      the breast received adequate dose. Isodose distributions for 6 MV X-rays from
      three different accelerators differed by about +/- 3% for the "small" patient and
      more than +/- 5% for the "large" patient. For two different 6 MV machines of the
      same manufacturer, the isodose distribution agreed to within +/- 2% for all three
      planes for the "large" patient. CONCLUSION: The differences observed among the
      various TPS in this study were within +/- 5% for both the "small" and the
      "medium" patients while doses at the hot spot exhibit a larger variation. The
      large discrepancy observed in the off-axis plane for the "large" patient is
      largely due to the inability of most TPS to incorporate the collimator angles in
      the dose calculation. Only six systems involved agreed to within +/- 5% for all
      three patients in all calculation planes. The difference in dose distributions
      obtained with three accelerators from different manufacturers is probably due to
      the difference in beam profiles. On the other hand, the 6 MV X-rays from two
      different models of linear accelerators from the same manufacturer have similar
      beam characteristics and the dose distributions are within +/- 2% of each other
      throughout the breast volume. In general, multi-institutional breast treatment
      data can be compared within a +/- 5% accuracy.

PMID- 9240654
TI  - Validation of Monte Carlo dose calculations near 125I sources in the presence of
      bounded heterogeneities.
AB  - PURPOSE: Dose distributions around low energy (< 60 keV) brachytherapy sources,
      such as 125I, are known to be very sensitive to changes in tissue composition.
      Available 125I dosimetry data describe the effects of replacing the entire water
      medium by heterogeneous material. This work extends our knowledge of tissue
      heterogeneity effects to the domain of bounded tissue heterogeneities, simulating
      clinical situations. Our goals are three-fold: (a) to experimentally characterize
      the variation of dose rate as a function of location and dimensions of the
      heterogeneity, (b) to confirm the accuracy of Monte Carlo dose calculation
      methods in the presence of bounded tissue heterogeneities, and (c) to use the
      Monte Carlo method to characterize the dependence of heterogeneity correction
      factors (HCF) on the irradiation geometry. METHODS AND MATERIALS:
      Thermoluminescent dosimeters (TLD) were used to measure the deviations from the
      homogeneous dose distribution of an 125I seed due to cylindrical tissue
      heterogeneities. A solid water phantom was machined accurately to accommodate the
      long axis of the heterogeneous cylinder in the transverse plane of a 125I source.
      Profiles were obtained perpendicular to and along the cylinder axis, in the
      region downstream of the heterogeneity. Measurements were repeated at the
      corresponding points in homogeneous solid water. The measured heterogeneity
      correction factor (HCF) was defined as the ratio of the detector reading in the
      heterogeneous medium to that in the homogeneous medium at that point. The same
      ratio was simulated by a Monte Carlo photon transport (MCPT) code, using accurate
      modeling of the source, phantom, and detector geometry. In addition, Monte Carlo
      based parametric studies were performed to identify the dependence of HCF on
      heterogeneity dimensions and distance from the source. RESULTS: Measured and
      calculated HCFs reveal excellent agreement (< or = 5% average) over a wide range
      of materials and geometries. HCFs downstream of 20 mm diameter by 10 mm thick
      hard bone cylinders vary from 0.12 to 0.30 with respect to distance, while for an
      inner bone cylinder of the same dimension, it varies from 0.72 to 0.83. For 6 mm
      diameter by 10 mm thick hard bone and inner bone cylinders, HCF varies 0.27-0.58
      and 0.77-0.88, respectively. For lucite, fat, and air, the dependence of HCF on
      the 3D irradiation geometry was much less pronounced. CONCLUSION: Monte Carlo
      simulation is a powerful, convenient, and accurate tool for investigating the
      long neglected area of tissue composition heterogeneity corrections. Simple one
      dimensional dose calculation models that depend only on the heterogeneity
      thickness cannot accurately characterize 125I dose distributions in the presence
      of bone-like heterogeneities.

PMID- 9240655
TI  - Performance of a video-image-subtraction-based patient positioning system.
AB  - PURPOSE: We have developed and tested an interactive video system that utilizes
      image subtraction techniques to enable high precision patient repositioning using
      surface features. We report quantitative measurements of system performance
      characteristics. METHODS AND MATERIALS: Video images can provide a high
      precision, low cost measure of patient position. Image subtraction techniques
      enable one to incorporate detailed information contained in the image of a
      carefully verified reference position into real-time images. We have developed a
      system using video cameras providing orthogonal images of the treatment setup.
      The images are acquired, processed and viewed using an inexpensive frame grabber
      and a PC. The subtraction images provide the interactive guidance needed to
      quickly and accurately place a patient in the same position for each treatment
      session. We describe the design and implementation of our system, and its
      quantitative performance, using images both to measure changes in position, and
      to achieve accurate setup reproducibility. RESULTS: Under clinical conditions (60
      cm field of view, 3.6 m object distance), the position of static, high contrast
      objects could be measured with a resolution of 0.04 mm (rms) in each of two
      dimensions. The two-dimensional position could be reproduced using the real-time
      image display with a resolution of 0.15 mm (rms). Two-dimensional measurement
      resolution of the head of a patient undergoing treatment for head and neck cancer
      was 0.1 mm (rms), using a lateral view, measuring the variation in position of
      the nose and the ear over the course of a single radiation treatment. Three
      dimensional repositioning accuracy of the head of a healthy volunteer using
      orthogonal camera views was less than 0.7 mm (systematic error) with an rms
      variation of 1.2 mm. Setup adjustments based on the video images were typically
      performed within a few minutes. The higher precision achieved using the system to
      measure objects than to reposition them suggests that the variability in
      repositioning is dominated by the ability of the therapist to make small,
      controlled changes in the position of the patient. CONCLUSION: Using affordable,
      off-the-shelf technology, we have developed a patient positioning system that
      achieves repositioning accuracy normally associated with fractionated
      stereotactic systems. The technique provides real-time guidance and can be used
      to easily and quickly correct patient setup before every treatment, thus
      significantly reducing overall random positioning error. This improved
      positioning capability provides the precision required to realize the potential
      gains of conformal radiotherapy.

PMID- 9240656
TI  - Comparison of two head and neck immobilization systems.
AB  - PURPOSE: Accurate and reproducible patient positioning is fundamental to the
      success of fractionated radiotherapy. Concurrent with the introduction of three
      dimensional treatment planning capabilities at our institution, a head and neck
      immobilization system consisting of a standard foam rubber head support and three
      casting strips was replaced by a customized mask-based device. This study was
      performed to analyze the impact of the customized immobilization system on the
      reproducibility of patient setup during irradiation of head and neck and brain
      tumors. METHODS AND MATERIALS: Patients treated from 1989-1991 were immobilized
      with the strip system while those treated from 1991-1995 were immobilized with
      the mask. All treatment fields were simulated and were treated on a 4 MV (where
      the strip, but not the mask, system was fixed to the treatment couch) or > or = 6
      MV (where both the strip and the mask systems were fixed to the couch)
      accelerator. Port films were taken on the initial treatment day, routinely during
      treatment, and following shifts (requested). The number, magnitude, and direction
      of any isocenter shifts were retrospectively reviewed. A two-tailed chi square
      test was used to compare the differences in requested shifts in the strip and
      mask groups. RESULTS: The study population consisted of 69 brain tumor (35 strip,
      34 mask) and 71 head and neck (37 strip, 34 mask) patients. A total of 1575 port
      films representing 1070 isocenter placements were analyzed. No differences
      between the immobilization systems was seen on the 4-MV accelerator (where the
      mask system was not fixed to the couch). On the > or = 6-MV units, the frequency
      of shifts was 16.1% versus 6.2% (p = 0.002) with the strips and mask,
      respectively. Almost all of the benefit was seen in the routine films, where the
      corresponding rates were 13.2% and 4.1% (p = 0.007). For the mask system, the
      rate of requested shifts on routine films was 4.1% (8/197) for the > or = 6-MV
      units and 14.5% (24/166) for the 4-MV unit (p = 0.001). CONCLUSION: Using the
      frequency of physician-requested isocenter shifts as an indicator of the accuracy
      of patient repositioning, the newer mask system appears to be an improvement over
      the previously used strip system, provided that the immobilization device is
      secured to the treatment couch. Increased accuracy of daily setup provides an
      opportunity to improve the therapeutic ratio both by increased likelihood of
      tumor control and decreased risk of normal tissue complications.

PMID- 9240657
TI  - The University of Florida frameless high-precision stereotactic radiotherapy
      system.
AB  - PURPOSE: To develop and test a system for high precision fractionated
      stereotactic radiotherapy that separates immobilization and localization devices.
      METHODS AND MATERIALS: Patient localization is achieved through detection and
      digital registration of an independent bite plate system. The bite plate is made
      and linked to a set of six infrared light emitting diodes (IRLEDs). These IRLEDs
      are detected by an infrared camera system that identifies the position of each
      IRLED within 0.1 to 0.15 mm. Calibration of the camera system defines isocenter
      and translational X, Y, and Z axes of the stereotactic radiosurgery subsystem and
      thereby digitally defines the virtual treatment room space in a computer linked
      to the camera system. Positions of the bite plate's IRLEDs are processed
      digitally using a computer algorithm so that positional differences between an
      actual bite plate position and a desired position can be resolved within 0.1 mm
      of translation (X, Y, and Z distance) and 0.1 degree of rotation. Furthermore,
      bite plate misalignment can be displayed digitally in real time with
      translational (x, y, and z) and rotational (roll, pitch, and yaw) parameters for
      an actual bite plate position. Immobilization is achieved by a custom head mold
      and thermal plastic mask linked by hook-and-loop fastener tape. The head holder
      system permits rotational and translational movements for daily treatment
      positioning based on the bite plate localization system. Initial testing of the
      localization system was performed on 20 patients treated with radiosurgery. The
      system was used to treat 11 patients with fractionated stereotactic radiotherapy.
      RESULTS: Assessment of bite plate localization in radiosurgery patients revealed
      that the patient's bite plate could be positioned and repositioned within 0.5 +/-
      0.3 mm (standard deviation). After adjustments, the first 11 patients were
      treated with the bite plate repositioning error reduced to 0.2 +/- 0.1 mm.
      CONCLUSIONS: High precision stereotactic radiotherapy can be delivered using
      separate localization and immobilization systems. Treatment setup and delivery
      can be accomplished in 15 min or less. Advantages compared with standard systems
      require further study.

PMID- 9240658
TI  - Quality assurance system to correct for errors arising from couch rotation in
      linac-based stereotactic radiosurgery.
AB  - PURPOSE: The purpose of this project was the development of a quality assurance
      (QA) system that would provide geographically accurate targeting for linac-based
      stereotactic radiosurgery (LBSR). METHODS AND MATERIALS: The key component of our
      QA system is a novel device (Alignment Tool) for expedient measurement of gantry
      and treatment table excursions (wobble) during rotation. The Alignment Tool
      replaces the familiar pencil-shaped pointers with a ball pointer that is used
      with the field light of the accelerator to indicate alignment of beam and target.
      Wobble is measured prior to each patient treatment and analyzed together with the
      BRW coordinates of the target by a spreadsheet. The corrections required to
      compensate for any imprecisions are identified, and a printout generated
      indicating the floor stand coordinates for each couch angle used to place the
      target at isocenter. RESULTS: The Alignment Tool has an inherent accuracy of
      measurement better than 0.1 mm. The overall targeting error of our QA method,
      found by evaluating 177 target simulator films of 55 foci in 40 randomly selected
      patients, was 0.47 +/- 0.23 mm. The Alignment Tool was also valuable during
      installation of the floor stand and a supplemental collimator for the
      accelerator. CONCLUSIONS: The QA procedure described allows accurate targeting in
      LBSR, even when couch rotation is imprecise. The Alignment Tool can facilitate
      the installation of any stereotactic irradiation system, and can be useful for
      annual QA checks as well as in the installation and commissioning of new
      accelerators.

PMID- 9240659
TI  - Phantom assessment of lung dose from proton arc therapy.
AB  - PURPOSE: To compare resultant lung dose from proton arc therapy of the chest wall
      to that from electron arc therapy. METHODS AND MATERIALS: A 200 MeV proton beam
      from the Indiana University Cyclotron was range shifted and modulated to provide
      a spread out Bragg peak extending from the surface to a depth of 4 cm in water.
      The chest wall of an Alderson Rando phantom was irradiated by this beam,
      collimated to a 20 x 4 cm field size, while it rotated on a platform at
      approximately 1 rpm. For comparison, electron arc therapy of the Rando phantom
      chest wall was similarly performed with 12 MeV electrons and the resultant lung
      dose measured in each case. RESULTS: Dose-volume histograms for the Rando phantom
      left lung indicate a reduced volume of irradiated lung for protons at all dose
      levels and an integral lung dose that is half that for electron arc therapy in
      the case studied. In addition, a more uniform dose coverage of the target volume
      was achieved with the proton therapy. CONCLUSION: This study demonstrates a
      potential role for proton arc therapy as an alternative to electron arc therapy
      when lung dose must be minimized.

PMID- 9240660
TI  - Automated TLD system for tumor dose estimation from exit dose measurements in
      external beam radiotherapy.
AB  - PURPOSE: An automated TLD facility has been commissioned and calibrated, and
      techniques have been developed for the measurement of exit doses in external beam
      radiotherapy, to enable the routine estimation of delivered tumor doses. METHODS
      AND MATERIALS: An automated TLD system, originally intended for use in diagnostic
      radiology and radiation protection, has been evaluated and configured for the
      measurement of exit doses in radiotherapy. Linearity, optimum heating cycles and
      calibration procedures have been determined. At the photon energies used,
      encapsulated lithium fluoride chips provide insufficient buildup to ensure
      electronic equilibrium, necessitating calibration to allow for oblique exit
      surfaces. Expressions are derived to allow the calculation of delivered tumor
      doses. RESULTS: Under the calibration conditions described, the uncertainty in a
      single TLD measurement is approximately +/-2% (+/-1 standard deviation). Over the
      dose range 0.4-1.5 Gy, TL response is linear. The total heating cycle time,
      including annealing, is 75 s. Measurements of R(exit) (the ratio of exit dose
      with and without full backscatter), used in the estimation of tumor doses,
      decreases with field size for small fields and varies only slightly for field
      sizes greater than 7 x 7 cm. Lack of electronic equilibrium leads to a decrease
      in R(exit) with increasing exit surface obliquity for all energies considered.
      Application of the technique to a simulated treatment showed good agreement
      between estimated and applied tumor doses, when surface obliquity was taken into
      account. CONCLUSION: This work describes the commissioning and calibration of an
      automated TLD facility and demonstrates that exit surface measurements using TLD
      chips used under conditions where electronic equilibrium was not established,
      have the potential for identifying discrepancies in delivered tumor doses.

PMID- 9240661
TI  - Economic analyses.

PMID- 9240662
TI  - Is there a future for neutron capture therapy?

PMID- 9240663
TI  - Treatment of radiation-induced enterocolitis.

PMID- 9240665
TI  - Diagnostic accuracy of mammography and contrast-enhanced MR imaging in 238
      histologically verified breast lesions.
AB  - PURPOSE: To determine the sensitivity and specificity of X-ray mammography and of
      MR imaging in 238 consecutively operated breasts, and to correlate the findings
      to histopathological diagnosis. MATERIAL AND METHODS: Over 15 months, 220
      patients scheduled for breast surgery were examined consecutively, before
      surgery, by means of both mammography and MR imaging. Of the 220 patients, 18
      underwent bilateral breast surgery. The entire breast was examined by means of T1
      weighted transversal images using a 3D fast low-angle shot (FLASH) sequence. One
      pre- and 2 post-contrast scans were performed. Each breast was examined by means
      of mammography and 3 views were applied as routine. All palpable and
      mammographically suspect lesions were examined on additional images as microfocus
      magnification or spot compression. The two methods were evaluated independently
      of each other. RESULTS: In total, 145 malignant and 93 benign lesions were found
      at histopathological examination. The sensitivity of mammography was 89% and MR
      imaging 92%. The specificity was 72% in both methods. When the results of the 2
      methods were combined, a sensitivity of 99% and a specificity of 55% was
      achieved. CONCLUSION: Mammography and MR imaging seemed to complement each other
      to produce a high sensitivity. Unfortunately it is impossible at present to
      supplement mammography with MR imaging in each patient as a routine owing to the
      current technical and financial limitations.

PMID- 9240666
TI  - Interobserver variation in the interpretation of breast imaging. Comparison of
      mammography, ultrasonography, and both combined in the interpretation of palpable
      noncalcified breast masses.
AB  - PURPOSE: To analyze interobserver agreement in the interpretation of palpable
      noncalcified breast masses by means of mammography, ultrasonography, and a
      combination of both methods. MATERIAL AND METHODS: Mammograms and ultrasonograms
      of 100 benign breast masses and 100 malignant ones in 200 patients were
      retrospectively analyzed by 4 radiologists with experience in both imaging
      modalities. The images were analyzed independently and without knowledge of the
      final diagnosis. The analysis was performed in 3 sessions and used a 5-point
      rating scale for probability of malignancy. The interobserver variation was
      analyzed by means of observed agreement, kappa, and weighted kappa statistics
      based on the 5-point rating scale and a 3-level scale of the collapsed 5-point
      scale. The chi-square statistic was used for testing the equality of the kappa
      values. RESULTS: The overall kappa value on the 3-level scale was 0.48 (range
      0.37-0.61) for ultrasonography, 0.58 (range 0.52-0.66) for mammography, and 0.71
      (range 0.63-0.79) for the combined reading. The kappa values were statistically
      different for ultrasonography but did not differ significantly for the
      mammographic and combined readings. The combined reading showed higher kappa
      values than mammography alone, and the improvement was statistically significant
      for 3 of the 6 pairs of comparison. CONCLUSION: Radiologists differ substantially
      in their interpretations of mammograms and breast ultrasonograms. Agreement was
      highest in the combined reading, intermediate in mammography, and lowest in
      ultrasonography.

PMID- 9240667
TI  - Validation of a new system in quantitative coronary arteriography.
AB  - PURPOSE: To validate ANCOR, a new system in quantitative coronary arteriography
      (QCA). MATERIAL AND METHODS: The validation procedure was performed by comparing
      the calibration factors of catheters filled with saline solution or contrast
      medium, and by measuring precision-drilled lumens in a test phantom filled with
      contrast medium. The results were compared with a well established and validated
      system, CMS. RESULTS: The calibration test showed that the calibration factors in
      the saline and contrast-medium catheters differed only a few percent when
      catheters with diameters of 2.0-2.67 mm were used. The phantom test showed that
      both systems overestimated smaller and larger diameters than these. The best
      results for both systems were achieved in the middle-diameter range. CONCLUSION:
      The ANCOR and CMS systems gave comparable results in catheter calibrations and
      phantom tests.

PMID- 9240668
TI  - Ultrasound diagnosis of soft-tissue tumours in the hand and forearm. A
      prospective study.
AB  - PURPOSE: The aim of this prospective investigation was to evaluate the accuracy
      of certain ultrasound characteristics in diagnosing 5 common types of soft-tissue
      tumour in the hand and forearm. MATERIAL AND METHODS: The study comprised 50 soft
      tissue tumours, diagnosed by ultrasonography or histopathology as belonging to
      one of 5 soft-tissue tumour groups. The reported ultrasound diagnoses and the
      histopathological results were compared, and their sensitivity was calculated. A
      statistical model was applied to the prospective material. The first and second
      diagnostic alternatives were calculated for each specific tumour and for the
      whole prospective material. In the second part of this study, the prospective
      material was combined with a retrospective material of 96 tumours from a previous
      study. The combined material was analysed and the accuracy of the first and
      second diagnostic alternatives for each tumour and for the whole material was
      calculated. RESULTS: The sensitivity for the prospective material was 84%. The
      correct diagnosis predicted by the model for the combined material was 56% for
      the first alternative and 79% when the second alternative was included.
      CONCLUSION: Ultrasonography is useful in the diagnosis of soft-tissue tumours of
      the hand.

PMID- 9240664
TI  - Quantification of area at risk during coronary occlusion and reperfusion by means
      of MR perfusion imaging.
AB  - PURPOSE: Considerable clinical interest has focused on the size of ischemic
      myocardium. Fast MR imaging in conjunction with MR contrast media has the
      potential to identify hypoperfused and infarcted myocardium. This study used MR
      perfusion imaging to detect and quantify reperfused ischemic myocardium during a
      brief coronary occlusion and reperfusion, and to characterize the spatial extent
      of ischemic and reperfused ischemic myocardium relative to the "true" size of the
      area at risk as defined in histochemical morphometry at post mortem. MATERIAL AND
      METHODS: The left circumflex (LCX) coronary artery in 8 dogs was occluded for 15
      min followed by reperfusion in order to produce regional reversible myocardial
      ischemia. Perivascular Doppler probes were used to measure blood flow in the left
      anterior descending (LAD) and LCX coronary arteries. Fast inversion recovery
      prepared gradient-recalled-echo images were acquired to delineate the ischemic
      area during occlusion, and the area of reversible ischemic injury at 1 and 30 min
      of reperfusion. The size of ischemic and reperfused ischemic myocardium were
      compared with the area at risk as determined by histochemical morphometry at post
      mortem. RESULTS: During LCX occlusion, LCX flow decreased from 16+/-1 to 0.2+/
      0.1 ml/min. On contrast-enhanced images, ischemic myocardium was evident as a
      zone of relatively low signal intensity (SI) compared to normal myocardium. The
      size of the ischemic region was significantly smaller (30+/-2%) than at post
      mortem (36+/-3%; p<0.05). Immediately after reperfusion, LCX flow increased to
      83+/-11 ml/min and the contrast medium caused greater enhancement in the
      reperfused ischemic region than in the normal myocardium (69+/-3 vs 42+/-3
      arbitrary units; p<0.05). The increase in regional SI correlated closely with the
      increase in regional blood flow (r=0.73). At 1 min of reperfusion, the size of
      the reperfused ischemic myocardium was larger (48+/-3%, p<0.05) than the area at
      risk measured at post mortem. At 30 min of reperfusion, when the flow returned to
      baseline values (16+/-2 ml/min), contrast bolus produced no differential
      enhancement between the 2 myocardial territories. CONCLUSION: MR perfusion
      imaging has the potential to detect and quantify the size of ischemic myocardium
      and the region of post-occlusive hyperemia in the early reperfusion period. There
      is a significant direct linear relationship between the regional contrast
      enhancement of reperfused ischemic myocardium and the blood flow during post
      occlusive hyperemia. The difference in the size of the area at risk at MR
      perfusion imaging and at histochemical morphometry may reflect an influence of
      coronary collateral circulation.

PMID- 9240669
TI  - Computed radiography for characterisation of the weight-bearing knee.
AB  - PURPOSE: A new method for examining and measuring the weight-bearing knee in
      computed radiography (CR) and picture archiving and communication systems (PACS)
      has recently been developed on examination equipment used in QUESTOR Precision
      Radiography (QPR). QPR is a method for the standardised examination of the knee,
      and generates 9 angles (e.g. hip-knee-ankle (HKA) angle) and 10 distances,
      corrected for parallax and magnification. The aim of this present study was to
      evaluate the reproducibility of this newly developed method and to determine
      intra- and interobserver variation in its measurements. MATERIAL AND METHODS: The
      images were generated on a CR system, archived, and transferred to a
      multimodality work-station that had a monitor with a resolution of 1280x1024
      (1kx1k). Photostimulable phosphor plates were used to generate images with a
      matrix of 1760x2140 pixels (pixel size 0.2 mm, corresponding resolution 2.5
      1p/mm). Ten volunteers without knee problems were examined twice, bilaterally, by
      2 different radiology technologists. RESULTS: The total reproducibility of the
      method was good, offering an HKA reproducibility of +/-2.64 degrees in slight
      flexion and +/-1.62 degrees in extension, at 95% confidence. The intra- and inter
      observer variations were low with a reduction of the intra-observer variations in
      all measurements (except one) by a factor of 2.8 on average compared with the
      original QPR method for conventional film-screen radiography. CONCLUSION: When
      QPR is modified for CR, it fulfils the requirement of reproducibility in
      measurements of the weight-bearing knee.

PMID- 9240670
TI  - Width of the medial tibiotalar joint.
AB  - PURPOSE: To determine the extent to which the width of the space in the medial
      tibiotalar joint depends on plantar flexion. MATERIAL AND METHODS: Thirty healthy
      volunteers were studied by means of a.p. roentgenograms of the left ankle both in
      a neutral position and in plantar flexion. RESULTS: The medial joint space showed
      significant widening (average 0.65 mm) between the neutral position and plantar
      flexion. CONCLUSION: When ankle joint injuries are studied on radiographs, the
      position of the foot must be taken into consideration.

PMID- 9240671
TI  - Diagnosis of Hill-Sachs lesion of the shoulder. Comparison between
      ultrasonography and arthro-CT.
AB  - AIM: The Hill-Sachs lesion is a compression fracture caused by impact on the
      trabeculae of the humeral head during anterior glenohumeral dislocation. The
      early and accurate identification of patients who risk recurrence of shoulder
      dislocation requires a suitable screening method. This should be characterized by
      high sensitivity and specificity, low cost, and repeatability. MATERIAL AND
      METHODS: The results of ultrasound examination as a screening method were
      evaluated, the indicator being the identification of the Hill-Sachs lesion. Using
      ultrasonography and conventional radiological techniques, and double contrast CT
      (arthro-CT), we studied 60 patients with posttraumatic instability of the
      shoulder. RESULTS: Against arthro-CT as the true standard, ultrasonography showed
      a sensitivity of 95.6%, specificity of 92.8%, and diagnostic accuracy of 95%.
      CONCLUSION: Ultrasonography is an acceptable screening examination for recurrent
      scapulohumeral dislocation and should be applied prior to other techniques of
      investigation such as arthro-CT or MR imaging.

PMID- 9240672
TI  - CT measurement of anteversion in the femoral neck. The influence of femur
      positioning.
AB  - PURPOSE: To evaluate CT methods of measuring anteversion in the femoral neck with
      respect to measurement accuracy and with respect to the influence exerted by
      different femoral shaft positions; and to describe a new CT measurement concept
      that introduces a mathematical adjustment for different femoral shaft positions.
      The new technique facilitates the taking of measurements in patients who cannot
      be correctly positioned in traditional methods. MATERIAL AND METHODS: CT
      examinations of previously measured anteversions in the femoral neck were
      reviewed in retrospect in 30 patients with fractures of the femoral neck. The
      position of the femoral shaft was assessed. A reference angle was compared with
      direct traditional measurements and with measurements adjusted for the actual
      position of the femoral shaft by means of a 3D mathematical reconstruction.
      Reproducibility and inter- and intraobserver variability were assessed in 10
      cases. RESULTS: All femurs varied in position within the gantry. The mean
      difference between the direct CT measurement and the adjusted CT measurement
      compared to the reference angle were -8.8 degrees (range -35.0-16.3 degrees) and 
      0.1 degrees (range -1.4-1.4 degrees), respectively. For the adjusted CT method,
      reproducibility and inter- and intraobserver variability were 1.4 degrees, 1.6
      degrees and 1.4 degrees (SD of difference), respectively. CONCLUSION: CT
      measurement of femoral anteversion in clinical practice can only be accurate when
      corrected for variation in the position of the femoral shaft.

PMID- 9240673
TI  - Dynamic scintigraphy of bone and bone marrow in multiple myeloma patients with
      bone-marrow transplants.
AB  - PURPOSE: To determine whether dynamic registration at bone and bone-marrow
      scintigraphy produces additional information compared to subsequent static
      registrations of bone-marrow transplants in multiple myeloma patients. MATERIAL
      AND METHODS: In a prospective study, 8 dynamic bone and 6 dynamic bone-marrow
      scintigraphies were performed in 10 patients. The dynamic scintigraphies were
      compared with conventional radiography, MR images, and static scintigraphies of
      bone and bone marrow. RESULTS: No additional information was revealed by the
      dynamic registration method; on the contrary, 4 of the 8 known lesions were not
      discerned at dynamic registration. An incidental observation was that the time
      activity curves of both radiopharmaceuticals had a specific pattern. CONCLUSION:
      Dynamic registration at bone and bone-marrow scintigraphy was not useful for
      detecting disease in multiple myeloma lesions.

PMID- 9240675
TI  - Blunt pancreatic trauma. Role of CT.
AB  - PURPOSE: To define the evolution patterns of blunt pancreatic trauma, and to
      point out the CT features most significant for the diagnosis. MATERIAL AND
      METHODS: Ten cases of pancreatic trauma, observed over a period of about 10
      years, were analyzed in retrospect. The cases were divided into 3 groups
      according to the time that had elapsed between trauma and first CT: early phase
      (within 72 h: n=3/10); late phase (after 10 days: n=3/10); and following
      pancreatic drainage (n=4/10). RESULTS: In the early phase, one case showed a
      blood collection surrounding the pancreatic head and duodenum, and displacing the
      mesenteric vessels to the left. In the 2 other cases it was possible to
      demonstrate a tear in the pancreas at the neck, perpendicular to the main
      pancreatic axis. In the late phase in all 3 cases, one cystic lesion was present
      at the site of the tear, either surrounding the gland or embedded - more or less
      deeply - within the parenchyma. One of the lesions subsided spontaneously; the 2
      others required surgery. In the postoperative phase, an external fistula was
      demonstrated in 2 cases following percutaneous drainage of pancreatic cysts; the
      fistula was fed by a cystic lesion in the pancreatic neck. In the 2 other cases a
      pseudocyst developed. CONCLUSION: Early demonstration of a parenchymal tear was
      difficult. At a later stage the diagnosis was easier owing to the demonstration
      of cystic lesions within the parenchyma at the site of the tear. The surgical
      drainage of this lesion does not usually lead to healing since an external
      fistula or a pseudocyst may develop.

PMID- 9240674
TI  - Dual-energy X-ray absorptiometric densitometry in osteoarthritis of the hip.
      Influence of secondary bone remodeling of the femoral neck.
AB  - PURPOSE: The aim of this study was to evaluate the influence of buttressing on
      bone densitometry measurements in the femoral neck, in Ward's triangle, and in
      the greater trochanter. In addition, we attempted to establish the length of the
      femoral axis (FAL) and the true length of the femoral neck (FNL) as potential
      correlates with osteoarthritis (OA) or with buttressing. MATERIAL AND METHODS:
      Our study comprised 101 hips in 68 adult patients. Conventional radiographs of
      the hip joints were obtained in order to assess the presence and extent of OA by
      means of the 6-step grading system introduced in 1990 by CROFT et al., and in
      order to measure the cortical thickness at the medial aspect of the femoral neck.
      In addition, FAL and FNL were measured. All patients underwent dual energy x-ray
      absorptiometry so that bone density could be assessed in the femoral neck, in
      Ward's triangle, and in the greater trochanter. The Spearman rank correlation was
      used to compare the measurements. RESULTS: Statistical analysis showed a
      significant positive correlation between cortical thickness and bone density in
      the femoral neck and in Ward's triangle. No correlation was found between
      cortical thickness and bone density in the greater trochanter, nor between
      cortical thickness and OA, FNL, and FAL, nor between OA and bone density, FNL,
      and FAL. CONCLUSION: Buttressing influenced our bone density measurements in the
      femoral neck and in Ward's triangle. It did not affect the region of the greater
      trochanter which may therefore be the best region of interest for a long-term
      follow-up of bone density in patients with OA.

PMID- 9240676
TI  - Endoscopically inserted stent as treatment for pancreatic ascites. A case report.
AB  - After 3 weeks of unsuccessful conservative treatment, a pancreatic fistula with
      peritoneal fluid collection was managed with the endoscopic insertion of a stent
      from the duodenum into the pancreatic duct beyond the origin of the fistula. The
      patient who presented contraindications at surgery, made a remarkable recovery.
      At stent-retrieval, however, a stricture formation was seen in the main
      pancreatic duct.

PMID- 9240677
TI  - CT arterial portography and CT arteriography with a triple-lumen balloon
      catheter.
AB  - PURPOSE: To evaluate the usefulness of the triple-lumen balloon catheter in the
      serial performance of CT arterial portography (CT-AP) and CT arteriography (CT
      A). MATERIAL AND METHODS: A combined CT-AP and CT-A examination of 58 patients
      was carried out in which a cobra-type triple-lumen balloon catheter was used. CT
      AP was performed by injecting contrast medium either into the splenic artery
      through a side-hole in the catheter proximal to the balloon inflated in the
      common hepatic artery, or into the superior mesenteric artery through an end-hole
      in the catheter. Then CT-A was serially performed by delivering contrast medium
      either to the common hepatic artery or the proper hepatic artery from the end
      hole, or to the accessory right hepatic artery through a side-hole proximal to
      the inflated balloon. RESULTS: Sufficient CT-APs were obtained in 53 of the 58
      patients (91%), CT-A in 42 (72%), and both in 42 (72%). Incomplete CT-AP was due
      to technical failure or anatomical anomaly, as was incomplete CT-A. No
      complications were seen. CONCLUSION: The triple-lumen balloon catheter technique
      is useful and convenient in the serial performance of CT-AP and CT-A.

PMID- 9240678
TI  - Transjugular intrahepatic portosystemic shunt (TIPS). Thrombogenicity in stents
      and its effect on shunt patency.
AB  - PURPOSE: To compare the thrombogenicity and patency of the Palmaz stent and the
      Wallstent, and to evaluate the effect of periprocedural heparin therapy in
      cirrhotic patients with maintained coagulation capacity who receive a
      transjugular intrahepatic portosystemic shunt (TIPS). MATERIAL AND METHODS:
      Twenty-four patients were randomized into 4 groups of 6 patients. Each received a
      Palmaz-stent or Wallstent TIPS with or without periprocedural heparin therapy.
      The groups receiving periprocedural heparin were given 24 U/kg b.w. just before
      stent placement, followed by 24 h therapeutic i.v. heparin. After 24 hours, all
      patients received i.v. heparin for 1 week followed by subcutaneous treatment with
      low-molecular-weight heparin (0.3 ml/day) for another 4 weeks. Stent
      thrombogenicity was determined scintigraphically after i.v. injection of 120-290
      mBq of 99mTc-labeled platelets at the time of stent placement and expressed as
      the stent/heart ratio. Shunt patency was assessed by duplex sonography and
      confirmed radiologically. RESULTS: The aggregation ratio was highest 90 min after
      stent implantation. Wallstents showed a significantly higher ratio than Palmaz
      stents. Heparin reduced the ratio in patients with a Wallstent (-41%) but had no
      effect on Palmaz stents. Patients with a Wallstent without heparin had a higher
      rate of early shunt insufficiency (66.6%) than the other patients (0-16.6%).
      Primary assisted long-term patency was similar in the 4 groups. CONCLUSION:
      Wallstents were more thrombogenic than Palmaz stents and gave a significantly
      higher risk of early shunt insufficiency in cirrhotic patients with maintained
      coagulation capacity. Periprocedural heparin was effective in the prevention of
      shunt insufficiency and is therefore indicated in such patients.

PMID- 9240679
TI  - Optimal MR protocol for hepatic hemangiomas. Comparison of conventional spin-echo
      sequences with T2-weighted turbo spin-echo and serial gradient-echo (FLASH)
      sequences with gadolinium enhancement.
AB  - PURPOSE: To compare conventional spin-echo (SE) sequences with T2-weighted turbo
      SE and serial gadolinium-enhanced T1-weighted FLASH sequences in the detection
      and characterization of hepatic hemangiomas, and to describe the enhancement
      characteristics of the lesions on dynamic MR imaging. MATERIAL AND METHODS: Forty
      two patients with 66 hemangiomas were studied at 1.0 T or 1.5 T by using
      conventional SE sequences (T1-weighted, T2-weighted, and heavily T2-weighted), T2
      weighted turbo SE sequences, and breath-hold T1-weighted FLASH sequences acquired
      before, immediately after, and 1, 2, 3, 5, and 10 min after injection of a bolus
      of gadopentetate dimeglumine. Images were quantitatively analyzed for lesion-to
      liver contrast-to-noise (C/N) ratios, and qualitatively analyzed for lesion
      conspicuity. The enhancement pattern and the rapidity of enhancement were
      analyzed in small (<15 mm), medium (15-39 mm), and large (>39 mm) hemangiomas.
      RESULTS: In T2-weighted images, T2-weighted turbo SE and heavily T2-weighted SE
      images had higher C/N ratios than T2-weighted SE images (p=0.003). Lesion
      conspicuity was not significantly different in these 3 sequences (p=0.307). In T1
      weighted images, T1-weighted FLASH images had higher C/N (p<0.001) and also
      better lesion conspicuity (p<0.001) than T1-weighted SE images. Immediate uniform
      enhancement was seen in 43% of small hemangiomas (9 of 21 lesions), and
      persistent central hypointensity was seen in 73% of large hemangiomas (11 of 15
      lesions). Rapid enhancement was seen in 62% of small hemangiomas (13 of 21
      lesions) and in 31% of medium or large hemangiomas (14 of 45 lesions).
      CONCLUSION: Further clinical study is needed for evaluating the differential
      diagnostic advantages of turbo SE T2-weighted imaging compared to the calculation
      of T2-values by means of a SE T2-weighted sequence. However, the results of the
      present study suggest that T2-weighted turbo SE imaging and precontrast and
      serial gadolinium-enhanced FLASH imaging have the potential to replace
      conventional SE imaging in the evaluation of hepatic hemangiomas.

PMID- 9240680
TI  - Characterization of sonographically indeterminate ovarian tumors with MR imaging.
      A logistic regression analysis.
AB  - PURPOSE: The goal of this study was to maximize the discrimination between benign
      and malignant masses in patients with sonographically indeterminate ovarian
      lesions by means of unenhanced and contrast-enhanced MR imaging, and to develop a
      computer-assisted diagnosis system. MATERIAL AND METHODS: Findings in precontrast
      and Gd-DTPA contrast-enhanced MR images of 104 patients with 115 sonographically
      indeterminate ovarian masses were analyzed, and the results were correlated with
      histopathological findings. Of 115 lesions, 65 were benign (23 cystadenomas, 13
      complex cysts, 11 teratomas, 6 fibrothecomas, 12 others) and 50 were malignant
      (32 ovarian carcinomas, 7 metastatic tumors of the ovary, 4 carcinomas of the
      fallopian tubes, 7 others). A logistic regression analysis was performed to
      discriminate between benign and malignant lesions, and a model of a computer
      assisted diagnosis was developed. This model was prospectively tested in 75 cases
      of ovarian tumors found at other institutions. RESULTS: From the univariate
      analysis, the following parameters were selected as significant for predicting
      malignancy (p< or =0.05): a solid or cystic mass with a large solid component or
      wall thickness greater than 3 mm; complex internal architecture; ascites; and
      bilaterality. Based on these parameters, a model of a computer-assisted diagnosis
      system was developed with the logistic regression analysis. To distinguish benign
      from malignant lesions, the maximum cut-off point was obtained between 0.47 and
      0.51. In a prospective application of this model, 87% of the lesions were
      accurately identified as benign or malignant. CONCLUSION: Benign and malignant
      ovarian lesions can be distinguished in most sonographically indeterminate
      lesions by means of parameters obtained from contrast-enhanced MR imaging.

PMID- 9240681
TI  - Defaeco-peritoneography in the diagnosis of rectal intussusception and rectal
      prolapse.
AB  - PURPOSE: The aim of the present study was to evaluate the use of defaeco
      peritoneography in diagnosing rectal intussusception as distinct from mucosal
      folds in the rectum, and rectal prolapse as distinct from mucosal prolapse.
      MATERIAL AND METHODS: Fifty-seven patients with defaecation disorders were
      examined by means of defaeco-peritoneography. RESULTS: Twenty-three patients had
      rectal intussusception and 7 patients had rectal prolapse at defaeco
      peritoneography. All these patients had a rectal peritoneocele in the serosal
      ring-pocket of the rectal intussusception or in the rectal prolapse. Twenty-seven
      patients had neither rectal intussusception nor rectal prolapse and none of these
      patients had a rectal peritoneocele. CONCLUSION: The present study demonstrated
      that only patients with a rectal intussusception or rectal prolapse have a rectal
      peritoneocele. Defaeco-peritoneography therefore offers correct diagnosis of
      rectal intussusception as distinct from mucosal folds in the rectum, and of
      rectal prolapse as distinct from mucosal prolapse.

PMID- 9240682
TI  - Magnetic iron oxide particles coated with carboxydextran for parenteral
      administration and liver contrasting. Pre-clinical profile of SH U555A.
AB  - RATIONALE AND OBJECTIVES: To evaluate the physical and pharmacological profiles
      of SH U555A, a suspension of magnetic iron oxide particles that is designed to
      enhance the visualization of liver tumors and metastases. MATERIAL AND METHODS:
      Chemical and physical methods were used to characterize the size and structure of
      these magnetic iron oxide particles in aqueous solution. The biodistribution and
      pharmacokinetics of the particles were studied in mice, rats and dogs. The
      imaging efficacy of the particles was demonstrated by MR imaging in rat liver
      tumors RESULTS: The SH U555A particles consist of low-molecular-weight
      carboxydextran-coated iron oxides predominantly of the gamma-Fe2O3 form with a
      hydrodynamic diameter ranging from 57-59 nm and strong T2 relaxivity of 164
      liters x mmol(-1) x s(-1) (water, 0.47 T). In rats the particles exhibited a dose
      dependent half-life of between 2 and 3 days in the liver at a dose of 20 micromol
      Fe/kg and a shorter half-life at lower doses. No major side effects were found.
      In a rat tumor model the tumor-to-liver contrast was markedly improved after i.v.
      administration of SH U555A. At a dose of 14 micromol Fe/kg the half-maximal
      contrast-effect was obtained even in nonoptimized T1-weighted spin-echo images.
      CONCLUSION: SH U555A is a superparamagnetic MR contrast agent for i.v.
      administration and has substantial potential for the demarcation of liver tumors.

PMID- 9240683
TI  - Peak systolic velocity, resistance index and pulsatility index. Variations in
      measuring a pre-recorded videotape.
AB  - PURPOSE: To study variation in the process of measuring Doppler ultrasound (US)
      wave forms. MATERIAL AND METHODS: Eleven radiologists measured peak systolic
      velocity (PSV), resistance index (RI), and pulsatility index (PI) from a pre
      recorded videotape. The wave forms were taken from the carotid, brachial, celiac,
      and renal interlobar arteries in a healthy volunteer. Each radiologist obtained
      measurements 10 times from a freely chosen wave form of 10 wave forms (10-beat
      series) and then a further set of measurements also 10 times from a specific wave
      form (1-beat series). RESULTS: There was a significant variation in all the PSV,
      RI and PI values measured, both in the 1-beat series and in the 10-beat series.
      The greatest variation was seen in the PI values: up to 5.1-fold. Both
      intraobserver and interobserver reproducibilities were poor. CONCLUSION: The
      process of obtaining measurements from an identified wave form is a major source
      of error in Doppler US studies. Special attention should be paid to this final
      phase of an examination. We recommend that measurements be obtained from more
      than one heart beat.

PMID- 9240684
TI  - MR evaluation of CSF fistulae.
AB  - PURPOSE: To evaluate the role of MR imaging in the localisation of cerebrospinal
      fluid (CSF) fistulae. MATERIAL AND METHODS: A total of 36 consecutive unselected
      patients with either clinically proven CSF leakage (n=26) or suspected CSF
      fistula (n=10) were prospectively evaluated by MR. All MR examinations included
      fast spin-echo T2-weighted images in the 3 orthogonal planes. Thin-section CT was
      performed following equivocal or negative MR examination. MR and CT findings were
      correlated with surgical results in 33 patients. RESULTS: CSF fistula was
      visualised as a dural-bone defect with hyperintense fluid signal continuous with
      that in the basal cisterns on T2-weighted images. MR was positive in 26 cases, in
      24 of which the fistula was confirmed surgically. In 2 patients the CSF leakage
      was directly demonstrated on MR. MR sensitivity of 80% compared favourably with
      the reported 46-81% of CT cisternography (CTC). No significant difference in MR
      sensitivity in detecting CSF fistula was found between active and inactive leaks
      CONCLUSION: MR is recommended as the first investigation for detecting a CSF
      fistula owing to its efficacy and to its freedom from the potential complications
      encountered with CTC.

PMID- 9240685
TI  - MR imaging of experimental subdural bleeding. Correlates of brain deformation and
      tissue water content, and changes in vital physiological parameters.
AB  - PURPOSE: To evaluate morphological and physiological changes during acute lethal
      subdural bleeding in 2 models of anaesthetized dogs. MATERIAL AND METHODS: In
      model I, blood from the aorta was led into a collapsed subdural rubber balloon
      while in model II, the blood was directed into the subdural compartment over the
      left cerebral frontoparietal lobe. Eight vital physiological parameters were
      continuously registered. MR imaging visualized the compression and displacement
      of cerebral tissue, and assessed the dynamic changes in cerebral tissue water.
      RESULTS: In model I, tissue herniation and compression of cerebral ventricles led
      to death at a haematoma volume corresponding to 8% of the intracranial volume. In
      model II, the extravasated blood progressed infratentorially and into the spinal
      sac with a volume that was 3 times larger than that of the lethal haematoma.
      Tissue water increased almost linearly during bleeding in both models.
      CONCLUSION: The high level of mortality after acute subdural haematoma is caused
      by a reduction in intracranial volume tolerance with a critical decrease in
      cerebral perfusion pressure, resulting in a fatal cerebral ischaemia.

PMID- 9240686
TI  - Influenza pandemic preparedness plan for the United States.
AB  - In preparation for the next influenza pandemic, a comprehensive and action
      oriented plan is presently under development that focuses on six major areas: (1)
      improvements in ongoing virologic and disease-based surveillance systems; (2)
      vaccination of high-priority target groups, and, given sufficient vaccine
      supplies, the entire US population; (3) liability programs for vaccine
      manufacturers and health care providers; (4) research to improve detection of new
      variants and to accelerate the availability of existing and novel vaccines and
      antiviral agents; (5) integrated, multicomponent communication systems for rapid
      information dissemination and exchange; and (6) emergency preparedness plans to
      provide for adequate medical care and maintenance of essential community
      services. The sudden and unpredictable emergence of pandemic influenza and its
      potential for causing severe health and social consequences dictate the need for
      close collaboration among a wide variety of organizations in both the public and
      private sectors.

PMID- 9240687
TI  - Surveillance for pandemic influenza.
AB  - Concerns that a new influenza strain may arise that would exhibit similar
      properties to the 1918-1919 pandemic virus prompted the decision in 1947 to
      establish a World Health Organization global program for influenza surveillance.
      This program has contributed greatly to understanding of the epidemiology of
      influenza and provides the basis for the timely updating of influenza vaccine
      formulations during interpandemic periods. The spread of pandemic influenza,
      however, is extremely rapid and, in 1957 and 1969, occurred before sufficient
      supplies of vaccine could be prepared and administered. Recent evidence regarding
      the origin of new influenza strains provides some opportunities for improving
      surveillance for pandemic influenza, but there is a danger that the benefits may
      be offset by even more rapid spread of a future pandemic due to changes in
      worldwide transportation and commerce.

PMID- 9240688
TI  - Predictions for future human influenza pandemics.
AB  - Will there be another human influenza pandemic? The certainty is that there will
      be, and the probability is that the virus will emerge from Eurasian aquatic bird
      reservoirs and involve reassortment between a human and avian strain, with
      accumulation of mutations or true recombinational events (or both) that will
      permit spread and pathogenicity among humans. This process will probably occur in
      pigs because they possess receptors for both avian and human influenza viruses,
      and emergence may occur in southern China. Prediction of the subtype is
      impossible, but there is a hypothesis based on seroarcheology that only H1, H2,
      and H3 subtypes can infect humans; however, it is arguable that H7 or H2 strains
      might be equally capable of infecting humans.

PMID- 9240689
TI  - Immunogenicity and reactogenicity of influenza subunit vaccines produced in MDCK
      cells or fertilized chicken eggs.
AB  - A tissue culture method using MDCK cells grown under serum-free conditions was
      developed to produce an inactivated influenza subunit vaccine. The first clinical
      data suggest it to be equal to the conventional egg-derived influenza subunit
      vaccine. In a double-blind controlled trial, 2 groups (n = 57 each) of adult
      volunteers were immunized with experimental bivalent influenza subunit vaccine
      derived from either MDCK cells or hens' eggs. Each vaccine contained 15 microg of
      hemagglutinin of influenza A/Taiwan/1/186 (H1N1) and 15 microg of hemagglutinin
      of B/Panama/45/90. No clinically relevant adverse reactions were observed in
      either vaccine group, and the incidence of systemic and local vaccine reactions
      was comparable in both groups. Standard hemagglutination inhibition antibody
      titers were determined using both MDCK- and egg-derived test antigens. The data
      reveal that both vaccines are safe and well-tolerated and meet the criteria for
      immunogenicity as stated in the European Community's "Harmonisation of
      Requirements for Influenza Vaccines."

PMID- 9240690
TI  - Effects of glycosylation on the properties and functions of influenza virus
      hemagglutinin.
AB  - The influenza virus A hemagglutinin (HA) is a trimeric glycoprotein that contains
      3-9 N-linked glycosylation sequons per subunit, depending on the strain. The
      location of these sites is determined by the nucleotide sequence of the HA gene,
      and, since the viral genome is replicated by an error-prone RNA polymerase,
      mutations, which add or remove glycosylation sites, occur at a high frequency.
      Mutations that are not lethal to the virus add to the structural diversity of the
      virus population. Factors that determine the glycosylation of the HA are reviewed
      herein, as are the effects of host-specific glycosylation on receptor binding,
      fusion activity, and antigenic properties of the virus. Effects of host-specific
      glycosylation and selection on virulence and on vaccine efficacy and surveillance
      are discussed. In addition, inadequacies in our understanding of HA glycosylation
      and its effects on host range are emphasized.

PMID- 9240691
TI  - Perspectives on pandemics: a research agenda.
AB  - During the 20th century, indisputable pandemics of influenza occurred in 1918,
      1957, and 1968. The pandemics of 1957 (A/H2N2) and 1968 (A/H3N2) were associated
      with major antigenic changes in the virus, probably reflecting introduction by
      recombination of animal virus genes. The 1918 epidemic is beyond the reach of
      modern virology but, based on seroarcheology, appears to have been caused by a
      virus very similar to present swine (A/H1N1) influenza viruses. Changes in both
      principal antigens of the A/H1N1 subtype in 1947 resulted in total vaccine
      failure and pandemic spread of virus. On the basis of three periods of prevalence
      in the 20th century, A/H1N1 may be the "default" human virus, although the 39
      year persistence of A/H3N2 to the present challenges this view. Only H1, H2, and
      H3 and N1 and N2 antigens have been found in human influenza viruses, but
      virologic history is too brief to preclude the contribution of other antigens to
      future pandemics.

PMID- 9240692
TI  - Prospects for pandemic influenza control with currently available vaccines and
      antivirals.
AB  - Since an influenza virus variant of pandemic potential may appear at any time,
      plans must be made to use currently available vaccines and antivirals most
      advantageously. Inactivated vaccines remain the principal intervention for the
      near future, and it can be assumed that quantities available at critical points
      in the epidemic will be limited unless advances are made in methods of vaccine
      production. Repeated demonstration of the effectiveness of vaccination of older
      persons in preventing hospitalization and death confirms that the traditional
      high-risk groups should be given priority. Since community transmission can be
      interrupted by vaccinating school-age children, this group may also be targeted.
      Antivirals in use and under development will almost certainly be active against
      the pandemic variant. Use during pandemics should be extensive but may be limited
      by the quantity of drugs available, the logistics of storage and distribution,
      and the possibility of side effects.

PMID- 9240693
TI  - Improvement of inactivated influenza virus vaccines.
AB  - Inactivated influenza virus vaccines (IVVs) are used for prevention of influenza
      and its complications. Present vaccines are immunogenic, of low reactogenicity,
      and protective, but protection has varied between 0% and 100%. Increasing the
      dose of hemagglutinin and neuraminidase antigens with purified proteins
      significantly increased serum and nasal antibody responses; however, trials with
      newer adjuvants have not shown increased serum antibody to levels comparable with
      those in earlier studies using oil emulsion adjuvants. IgA antibody responses in
      respiratory secretions were enhanced by the respiratory administration of IVVs,
      but IVVs by the oral route yielded varying results. IVVs appeared less effective
      for pandemic influenza in 1968 than in 1957. Since IVVs will be the major
      preventative measure for pandemic influenza in most countries, they need to be
      improved to provide better protection against pandemic and interpandemic
      influenza. Increasing the doses of hemagglutinin and neuraminidase, using
      adjuvants or immunomodulators, and administering IVVs by the mucosal route could
      improve the performance of these vaccines.

PMID- 9240694
TI  - Development of novel influenza virus vaccines and vectors.
AB  - Approaches to improve the efficacy of the current (killed) influenza virus
      vaccines include the generation of cold-adapted and genetically engineered
      influenza viruses containing specific attenuating mutations. It is hoped that
      these genetically altered viruses, in which the hemagglutinin and neuraminidase
      genes from circulating strains have been incorporated by reassortment, can be
      used as safe live influenza virus vaccines to induce a long-lasting protective
      immune response in humans. In addition, genetically engineered influenza viruses
      may provide a means for expressing foreign antigens. Immunization of mice with
      recombinant influenza and vaccinia viruses expressing specific antigens of
      Plasmodium yoelii resulted in a dramatic protective immune response against
      malaria in this model. Mice immunized with recombinant influenza viruses
      expressing human immunodeficiency virus (HIV) epitopes generated long-lasting HIV
      specific serum antibodies and secretory IgA in the secretory nasal, vaginal, and
      intestinal mucosa. These results suggest that genetically engineered influenza
      viruses may be developed for use as live virus vaccines against influenza as well
      as other diseases.

PMID- 9240695
TI  - DNA immunization for influenza virus: studies using hemagglutinin- and
      nucleoprotein-expressing DNAs.
AB  - DNA-based immunizations have been used to analyze the ability of DNA-expressed
      hemagglutinin (HA) and nucleoprotein (NP) to protect BALB/c mice against a
      homologous influenza virus, A/PR/8/34 (H1N1), challenge. The HA DNA, but not the
      NP DNA, protected mice against the lethal viral challenge. For the HA DNA, single
      gene gun inoculations of 0.04 microg and boosted inoculations of 0.004 microg of
      DNA raised complete protection. For the NP DNA, boosted gene gun immunizations of
      0.4 microg of DNA and boosted intradermal or intramuscular injections of 50
      microg of DNA failed to protect. The protection elicited by the HA DNA vaccine
      correlated with the titers of neutralizing antibody.

PMID- 9240696
TI  - Antivirals for pandemic influenza.
AB  - Amantadine and rimantadine share features that would make them useful agents in
      responding to pandemic influenza. These include an antiviral spectrum
      encompassing influenza A viruses, favorable pharmacokinetics, a potential for
      stockpiling supplies, and documented prophylactic and therapeutic effectiveness
      in pandemic influenza. However, current production capability is insufficient to
      provide adequate drug for mass chemoprophylaxis in the event of vaccine
      unavailability. The risk of adverse drug effects, particularly central nervous
      system side effects, which occur more often with amantadine than rimantadine, and
      potential drug interactions are additional concerns. Short-course treatment of
      ill persons would provide symptom benefit, but convincing evidence that early
      antiviral treatment reduces bacterial and other influenza complications is
      currently lacking. Drug-resistant viruses emerge during therapy, appear to be
      fully pathogenic, and are transmissible to close contacts. Influenza
      neuraminidase inhibitors are promising investigational agents, but remaining
      issues include prophylactic efficacy, cost, efficient administration, and
      resistance emergence.

PMID- 9240697
TI  - Design of aromatic inhibitors of influenza virus neuraminidase.
AB  - Structure-based drug design, a terminology used to describe rational drug design
      by complementing the structure, spatially and chemically, of the target
      macromolecule, is rapidly developing as one of the innovative approaches to drug
      discovery. A growing volume of protein structure data and new techniques of
      protein structure determination make this all possible. The method of structure
      based drug design and a specific example of the design of influenza virus
      neuraminidase is briefly presented. A whole new class of influenza virus
      neuraminidase inhibitors has been designed that can potentially be developed as
      antiinfluenza drugs.

PMID- 9240698
TI  - Selection of influenza A and B viruses for resistance to 4-guanidino-Neu5Ac2en in
      cell culture.
AB  - The reassortant influenza viruses, A/NWS-G70c with N9 neuraminidase (NA) and
      B/HK/8/73 (HG) with B/Lee/40 NA, were selected for resistance to 4-guanidino
      Neu5Ac2en (4-GuDANA) by passaging the virus in stepwise increases in the
      concentration of 4-GuDANA. In the NA of resistant viruses, the absolutely
      conserved Glu 119, which lies in a pocket beneath the active site of the enzyme
      and interacts with the guanidinium moiety of 4-GuDANA, was changed to Gly. The
      mutant NA was >200-fold more resistant to 4-GuDANA than was the wild-type enzyme.
      During 72 h in cell culture, resistant A and B viruses displayed much less NA
      activity than did wild-type viruses but did undergo multicycle replication. While
      emergence of resistance to 4-GuDANA has not been observed in vivo, these results
      demonstrate that the development of resistance is possible and can be mediated by
      a single amino acid change in the active site of the viral NA.

PMID- 9240699
TI  - Pandemic influenza: confronting a re-emergent threat. The 1976 experience.
AB  - The Swine Influenza Immunization Program began in January 1976 with an outbreak
      of swine influenza among trainees at Ft. Dix, New Jersey. The program ended in
      December 1976 after an increased incidence of Guillain-Barre syndrome was
      attributed to the vaccine. The issues and events of 1976 provide valuable lessons
      for the future. A thorough and objective review of the swine flu program should
      be a prerequisite for influenza pandemic planning. Strong consideration should be
      given to creating separate structures for risk assessment and risk management.
      Risk assessment estimates the probability of a pandemic, the options available
      for control, and the relative benefits of those options as situations change.
      Risk management is the political response to that assessment.

PMID- 9240700
TI  - Panel summary of international pandemic influenza plans.

PMID- 9240701
TI  - Helical/spiral computed body tomography.

PMID- 9240702
TI  - The differential diagnosis of early inferior vena caval opacification on dynamic
      CT.

PMID- 9240703
TI  - FDG PET characterization of renal masses: preliminary experience.
AB  - OBJECTIVE: This study was undertaken to evaluate the potential efficacy of
      fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) to
      detect renal tumours and to characterize indeterminate renal cysts. SUBJECTS AND
      METHODS: Twenty-six PET scans were performed in 21 patients (14 PET scans in 10
      patients with malignant renal tumours and 12 PET scans in 11 patients with
      Bosniak type 3 indeterminate renal cysts). Pathological proof was obtained in 18
      of 21 patients (10 with solid neoplasms, eight with indeterminate cysts). Imaging
      was performed 1 h after injection of 5-10 mCi of FDG with IV administration of
      Lasix (10 mg) 20 mins after injection. Two consecutive 9.7-cm image segments were
      scanned to cover the entire renal areas. RESULTS: PET accurately depicted solid
      neoplasms as areas of increased uptake in nine of 10 patients. Bilateral renal
      cell carcinomas were missed in one diabetic patient. All but one indeterminate
      renal cysts were correctly classified as benign (photopenic areas), but an
      indeterminate cyst with a 4-mm papillary neoplasm was wrongly classified as
      benign. There were no false positive PET interpretations. The mean tumour-to
      kidney ratio was 3.0 for malignant lesions. CONCLUSION: We conclude that FDG PET
      scanning shows promise in the evaluation of indeterminate renal cysts. A positive
      PET scan in the appropriate clinical setting obviates the need for cyst
      aspiration. A negative PET scan in conjunction with a negative cyst aspiration
      offers confirmatory evidence of benignity. Our preliminary results are
      encouraging and further work is ongoing.

PMID- 9240704
TI  - Dynamic MR imaging of the breast combined with analysis of contrast agent
      kinetics in the differentiation of primary breast tumours.
AB  - OBJECTIVE: To assess dynamic Gd-DTPA-enhanced magnetic resonance (MR) imaging in
      the diagnosis of primary breast pathology, and to test the hypothesis that
      analysis of contrast agent kinetics increases specificity. METHODS: Forty-seven
      women underwent breast MR imaging using three-dimensional and dynamic spoiled
      gradient-recalled sequences. Image interpretation was based on the evaluation of
      lesion conspicuity, signal intensity, contour and enhancement pattern from the
      static acquisitions. Assessment of contrast kinetics was based on pixel-by-pixel
      analysis of the dynamic data. A two-compartment model described by three
      parameters (amplitude of uptake, exchange rate and washout rate), and a three
      compartment model described by two parameters (permeability and exchange rate)
      were used. Regions of interest were drawn for all lesions found in the dynamic
      sections. Mean regional pixel values were calculated for each parameter and
      tested for diagnostic efficacy. RESULTS: Twenty-two malignant and 36 benign
      lesions were examined. Fibroadenomas accounted for 86% of the benign tumours.
      Image interpretation had a sensitivity of 0.95 and specificity of 0.86. The fat
      suppressed post-contrast images permitted good visualization of the contour and
      matrix characteristics of fibroadenomas, but all non-fibroadenomatous benign
      lesions were classified as indeterminate or suspicious. Significant differences
      were found between benign and malignant lesions in the amplitude of uptake (P =
      0.0008) and exchange rate (P < 0.00005) of the two-compartment model, and
      permeability (P=0.0001) and exchange rate (P < 0.00005) of the three-compartment
      model. However, image interpretation was superior to the isolated use of
      quantitative indices (P=0.02). The most discriminating parameters were the
      exchange rates of both models, with no significant difference between them.
      CONCLUSION: Assessment of lesion morphology is essential and probably sufficient
      for the differentiation of fibroadenomas from malignant tumours. However,
      specificity of conventional MR imaging may be much lower for other types of
      primary benign breast pathology. Analysis of Gd-DTPA kinetics improves the
      specificity obtained using simple enhancement measurements and can be used to
      produce parametric images that provide information about lesion heterogeneity,
      permeability and vascularity.

PMID- 9240705
TI  - The influence of previous films on screening mammographic interpretation and
      detection of breast carcinoma.
AB  - AIM: To establish if the availability of previous mammograms improves the
      detection rate of carcinomas and reduces supplementary examinations in the
      National Health Service Breast Screening Programme (NHSBSP). METHOD: Eight
      radiologists with varying experience but an interest in reporting mammograms
      reported 100 mammograms on two occasions, at least 1 month apart. In this
      selection of 100 mammograms we randomly inserted 12 abnormal films, with both
      benign and malignant changes present. These were chosen retrospectively with
      histological correlation of the abnormality. On the first occasion only the
      current films were reviewed, however, on the second occasion previous films were
      available for comparison. The films were viewed under standard viewing
      conditions, and the participants were asked to comment if they required further
      views or would refer the patient for either an ultrasound examination or surgical
      referral. RESULTS: Receiver operating curves (ROC) were constructed for the
      group's overall performance on each of the occasions and there was no difference
      in the curves. This indicates that the presence of previous films did not improve
      diagnostic accuracy. The presence of previous films did, however, lead to a
      significant reduction in the number of additional views and ultrasound
      examinations that would have been requested. The most significant reductions
      occurred in the group of normal mammograms. CONCLUSION: The presence of previous
      mammograms does not lead to an improvement in diagnostic accuracy. However, the
      presence of previous films led to significant reduction in additional
      examinations and ultrasound examinations.

PMID- 9240706
TI  - Defining the use of gadolinium enhanced MRI in the assessment of the
      postoperative lumbar spine.
AB  - A retrospective study of case notes and magnetic resonance imaging (MRI)
      examinations was performed to assess the value of gadolinium enhanced MRI in the
      investigation of persistent back pain following lumbar spine surgery in patients
      who have not had a discectomy for disc herniation. Gadolinium enhancement is
      commonly used during MRI of patients with persistent back pain following surgery
      and epidural scar is frequently identified in patients who have had a previous
      discectomy. However the value of gadolinium enhancement in patients without
      previous discectomy had not been addressed. One hundred sets of case notes were
      examined and 24 patients with an accurate history of previous lumbar spine
      surgery without discectomy were identified. The nature of surgery and the MRI
      findings were correlated in these patients. Epidural enhancement was identified
      at seven sites in six patients (engorged epidural venous plexus, three;
      enhancement adjacent to degenerate discs, two; enhancement adjacent to facets,
      two). In no case was epidural scarring involving nerve roots identified. We
      conclude that routine gadolinium enhancement is unnecessary in patients without a
      history of discectomy for disc herniation.

PMID- 9240707
TI  - Malignant splenic lymphoma: sonographic patterns, diagnosis and follow-up.
AB  - Six hundred and eighty patients with malignant lymphoma were studied by abdominal
      sonography during 1983 and 1993 at our institution. Abnormal splenic texture was
      noted in 101 patients (14,8%). Involvement of the spleen was confirmed
      histologically (n = 8), by sonographic follow-up (n = 82), and on the basis of
      the clinical course in the remaining patients. Of the 101 patients with splenic
      involvement, 34 had Hodgkin's disease, 38 had a low-grade non-Hodgkin's lymphoma
      and 29 a high-grade non-Hodgkin's lymphoma. Four different sonographic patterns
      were observed: (1) Diffuse involvement in 37 patients (pts) (36.6%). (2) Focal
      small nodular lesions in 39 pts (38.6%). (3) Focal large nodular lesions in 23
      pts (22,7%). (4) 'Bulky, disease' in two pts (1.9%). All of the high-grade
      lymphomas showed either large nodular (15/29) or small nodular (14/29) lesions.
      The diffuse or small nodular pattern was seen predominantly in low-grade
      lymphomas (35/38) and in Hodgkin's disease (31/34). CONCLUSION: A number of
      different patterns of splenic involvement in lymphoma can be demonstrated by
      ultrasound. Splenic sonographic patterns can be linked to histological lymphoma
      entities.

PMID- 9240708
TI  - Lobar or segmental consolidation on chest radiographs of patients with HIV
      infection.
AB  - PURPOSE: To correlate chest radiographic abnormalities with diagnoses in HIV
      infected patients presenting with acute respiratory symptoms and lobar or
      segmental consolidation. MATERIALS AND METHODS: Retrospective review of chest
      radiographs of 53 HIV infected patients with lobar or segmental consolidation,
      and their microbiological and cytological diagnoses. RESULTS: A specific
      diagnosis was made in 35 patients of which 12 had Pneumocystis carinii pneumonia
      (including four co-infections) and 23 had bacterial pneumonias (10 of these were
      due to Streptococcus pneumoniae and four to Mycobacterium tuberculosis).
      Microbiological and cytological tests were negative in 18 patients. Non-specific
      radiographic features included bronchial wall thickening (79%), reticulonodular
      or reticular change (55%), effusions (38%) and lymphadenopathy (25%); effusions
      favoured a bacterial aetiology. Ten of the 12 cases with P. carinii pneumonia had
      upper lobe consolidation (three of these had received inhaled pentamadine). Of 13
      other cases of upper lobe consolidation, eight were due to pyogenic infection and
      only one to M. tuberculosis alone. CONCLUSION: A wide variety of causative agents
      may produce lobar or segmental consolidation in HIV infected individuals, and the
      most common cause is bacterial infection. Where there is upper lobe consolidation
      P. carinii pneumonia should be considered in the differential diagnosis.

PMID- 9240710
TI  - Conversion of gastrostomy to transgastric jejunostomy in children.

PMID- 9240709
TI  - Primary intraosseous meningiomas of the skull.
AB  - The plain film, computed tomography (CT) and angiographic findings in 10 patients
      with primary intraosseous meningioma were reviewed and the differential diagnosis
      considered. In nine patients with benign primary intraosseous meningioma, the
      radiological findings revealed intraosseous expansile growth. In one patient with
      the malignant form of the tumour, osteolytic growth was evident on plain film and
      CT. In eight patients, the tumour tissue was hyperdense (65-85 HU) on the
      unenhanced CT images and striking enhancement was shown in seven. In five
      patients angiography showed that the external carotid artery fed the tumour,
      while in one the vasculature was normal. Benign primary intraosseous meningioma
      showed expansile growth and malignant tumour showed osteolytic growth. If a
      combination of the plain film, angiogram and CT findings is considered, a
      diagnosis of the benign tumour can be made and a diagnosis of benign meningioma
      can be suggested.

PMID- 9240711
TI  - Health service indicators for radiology departments: how meaningful are they?
AB  - The Health Service Indicator (HSI) for Radiology Services in the UK is
      represented by a cost per case figure based on annual expenditure and workloads
      in individual departments. These show significant variations betweeen departments
      for a number of predictable reasons. Detailed analysis shows good correlation
      between population-based radiology costs and workloads and that departments with
      low cost per case values have above average workloads. The usefulness of the HSI
      cost per case is limited to identification of departments with unduly high or low
      values, thus allowing such departments to critically appraise their staffing and
      workload levels. Taken at face value, they can easily be misinterpreted as a
      measure of cost-effectiveness.

PMID- 9240712
TI  - Case report: computed tomographic appearance of sclerosing peritonitis with gross
      peritoneal calcification.

PMID- 9240713
TI  - Case report: superior vena cava obstruction: unusual CT findings due to venous
      collaterals.

PMID- 9240714
TI  - Case report: the MRI diagnosis of bone marrow infarction in a child with
      leukaemia.

PMID- 9240715
TI  - Case report: successful treatment of bleeding jejunal varices using mesoportal
      recanalization and stent placement: report of a case and review of the
      literature.

PMID- 9240716
TI  - Dipstick testing of urine.

PMID- 9240717
TI  - The impact of core-biopsy on pre-operative diagnosis rate of screen-detected
      breast cancers.

PMID- 9240718
TI  - Double reporting of screening mammograms.

PMID- 9240719
TI  - American Society for Bone and Mineral Research annual meeting 1996. Fuller
      Albright Award. Frederic C. Bartter Award. William F. Neuman Award.

PMID- 9240720
TI  - Bone microdamage and skeletal fragility in osteoporotic and stress fractures.
AB  - The accumulation of bone microdamage has been proposed as one factor that
      contributes to increased skeletal fragility with age and that may increase the
      risk for fracture in older women. This paper reviews the current status and
      understanding of microdamage physiology and its importance to skeletal fragility.
      Several questions are addressed: Does microdamage exist in vivo in bone? If it
      does, does it impair bone quality? Does microdamage accumulate with age, and is
      the accumulation of damage with age sufficient to cause a fracture? The nature of
      the damage repair mechanism is reviewed, and it is proposed that osteoporotic
      fracture may be a consequence of a positive feedback between damage accumulation
      and the increased remodeling space associated with repair.

PMID- 9240721
TI  - Fractures attributable to osteoporosis: report from the National Osteoporosis
      Foundation.
AB  - To assess the cost-effectiveness of interventions to prevent osteoporosis, it is
      necessary to estimate total health care expenditures for the treatment of
      osteoporotic fractures. Resources utilized for the treatment of many diseases can
      be estimated from secondary databases using relevant diagnosis codes, but such
      codes do not indicate which fractures are osteoporotic in nature. Therefore, a
      panel of experts was convened to make judgments about the probabilities that
      fractures of different types might be related to osteoporosis according to
      patient age, gender, and race. A three-round Delphi process was applied to
      estimate the proportion of fractures related to osteoporosis (i.e., the
      osteoporosis attribution probabilities) in 72 categories comprised of four
      specific fracture types (hip, spine, forearm, all other sites combined)
      stratified by three age groups (45-64 years, 65-84 years, 85 years and older),
      three racial groups (white, black, all others), and both genders (female, male).
      It was estimated that at least 90% of all hip and spine fractures among elderly
      white women should be attributed to osteoporosis. Much smaller proportions of the
      other fractures were attributed to osteoporosis. Regardless of fracture type,
      attribution probabilities were less for men than women and generally less for non
      whites than whites. These probabilities will be used to estimate the total direct
      medical costs associated with osteoporosis-related fractures in the United
      States.

PMID- 9240722
TI  - Medical expenditures for the treatment of osteoporotic fractures in the United
      States in 1995: report from the National Osteoporosis Foundation.
AB  - Osteoporotic fractures are a significant public health problem, resulting in
      substantial morbidity and mortality. Previous estimates of the economic burden of
      osteoporosis, however, have not fully accounted for the costs associated with
      treatment of nonhip fractures, minority populations, or men. Accordingly, the
      1995 total direct medical expenditures for the treatment of osteoporotic
      fractures were estimated for all persons aged 45 years or older in the United
      States by age group, sex, race, type of fracture, and site of service (inpatient
      hospital, nursing home, and outpatient). Osteoporosis attribution probabilities
      were used to estimate the proportion of health service utilization and
      expenditures for fractures that resulted from osteoporosis. Health care
      expenditures attributable to osteoporotic fractures in 1995 were estimated at
      $13.8 billion, of which $10.3 billion (75.1%) was for the treatment of white
      women, $2.5 billion (18.4%) for white men, $0.7 billion (5.3%) for nonwhite
      women, and $0.2 billion (1.3%) for nonwhite men. Although the majority of U.S.
      health care expenditures for the treatment of osteoporotic fractures were for
      white women, one-fourth of the total was borne by other population subgroups. By
      site-of-service, $8.6 billion (62.4%) was spent for inpatient care, $3.9 billion
      (28.2%) for nursing home care, and $1.3 billion (9.4%) for outpatient services.
      Importantly, fractures at skeletal sites other than the hip accounted for 36.9%
      of the total attributed health care expenditures nationally. The contribution of
      nonhip fractures to the substantial morbidity and expenditures associated with
      osteoporosis has been underestimated by previous researchers.

PMID- 9240723
TI  - Platelet-derived growth factor stimulates sodium-dependent Pi transport in
      osteoblastic cells via phospholipase Cgamma and phosphatidylinositol 3' -kinase.
AB  - Inorganic phosphate (Pi) is a major regulator of cell metabolism. The Pi
      transport activity in the plasma membrane is a main determinant of the
      intracellular level of this ion. In bone-forming cells, Pi transport is important
      for the calcification of the bone matrix. In this study, the effect of platelet
      derived growth factor (PDGF) on Pi transport activity and the signaling mechanism
      involved in this cellular response were analyzed. The results indicate that PDGF
      is a potent and selective stimulator of sodium-dependent Pi transport in the
      mouse calvaria-derived MC3T3-E1 osteoblast-like cells. The change in Pi transport
      induced by PDGF-BB was dependent on translational processes and affected the Vmax
      of the Pi transport system. These observations suggested that enhanced Pi
      transport activity in response to PDGF resulted from insertion of newly
      synthesized Pi transporters in the plasma membrane. The role of activation of
      mitogen activated protein (MAP) kinase, phospholipase C (PLC)gamma or
      phosphatidylinositol 3-kinase (PI-3-kinase), in mediating this effect of PDGF,
      was investigated. A selective inhibitor of the PDGF receptor tyrosine kinase
      activity (CGP 53716) completely blocked PDGF-induced protein tyrosine
      phosphorylation of several proteins including the PDGF receptor, PLCgamma, MAP
      kinase, and association of the p85 subunit of PI-3'-kinase. Associated with this
      effect, the increase in Pi transport induced by PDGF was completely blunted by 5
      microM CGP 53716. Inhibition of MAP kinase activity by cAMP agonists did not
      influence Pi transport stimulation induced by PDGF. However, inhibitors of
      protein kinase C completely blocked this response. A selective inhibitor of PI-3
      kinase, LY294002, also significantly reduced this effect of PDGF. In summary,
      these results indicate that PDGF is a potent and selective stimulator of Pi
      transport in osteoblastic cells. The mechanism responsible for this effect is not
      mediated by MAP kinase but involves tyrosine phosphorylation-dependent activation
      of PLCgamma and PI-3-kinase.

PMID- 9240724
TI  - Pulsating fluid flow stimulates prostaglandin release and inducible prostaglandin
      G/H synthase mRNA expression in primary mouse bone cells.
AB  - Bone tissue responds to mechanical stress with adaptive changes in mass and
      structure. Mechanical stress produces flow of fluid in the osteocyte lacunar
      canalicular network, which is likely the physiological signal for bone cell
      adaptive responses. We examined the effects of 1 h pulsating fluid flow (PFF; 0.7
      +/- 0.02 Pa, 5 Hz) on prostaglandin (PG) E2, PGI2, and PGF2alpha production and
      on the expression of the constitutive and inducible prostaglandin G/H synthases,
      PGHS-1, and PGHS-2, the major enzymes in the conversion of arachidonic acid to
      prostaglandins, using mouse calvarial bone cell cultures. PFF treatment
      stimulated the release of all three prostaglandins under 2% serum conditions, but
      with a different time course and to a different extent. PGF2alpha was rapidly
      increased 5-10 minutes after the onset of PFF. PGE2 release increased somewhat
      more slowly (significant after 10 minutes), but continued throughout 60 minutes
      of treatment. The response of PGI2 was the slowest, and only significant after 30
      and 60 minutes of treatment. In addition, PFF induced the expression of PGHS-2
      but not PGHS-1. One hour of PFF treatment increased PGHS-2 mRNA expression about
      2-fold relative to the induction by 2% fresh serum given at the start of PFF.
      When the addition of fresh serum was reduced to 0.1%, the induction of PGHS-2 was
      8- to 9-fold in PFF-treated cells relative to controls. This up-regulation
      continued for at least 1 h after PFF removal. PFF also markedly increased PGHS
      activity, measured as the conversion of arachidonic acid into PGE2. One hour
      after PFF removal, the production of all three prostaglandins was still enhanced.
      These results suggest that prostaglandins are important early mediators of the
      response of bone cells to mechanical stress. Prostaglandin up-regulation is
      associated with an induction of PGHS-2 enzyme mRNA, which may subsequently
      provide a means for amplifying the cellular response to mechanical stress.

PMID- 9240725
TI  - Expression of tenascin-C in bones responding to mechanical load.
AB  - A number of early biochemical responses of bone cells to mechanical loading have
      been identified, but the full sequence of events from the sensing of strain to
      the formation of new bone is poorly characterized. Extracellular matrix proteins
      can modulate cell behavior and would be ideal molecules to amplify the early
      response to loading. The extracellular matrix protein, tenascin-C, supports
      differentiation of cultured osteoblast-like cells. The current study was carried
      out to investigate whether expression patterns of tenascin-C in loaded bones
      support a role for this protein as a mediator of the osteoregulatory response to
      loading. Tenascin-C expression was investigated by Northern blot analysis in rat
      ulnae subjected to an established noninvasive loading regimen engendering
      physiological strain levels. RNA extracted from loaded compared with
      contralateral control bones 6 h after loading showed a significant increase in
      tenascin-C transcript expression. The presence of tenascin-C was investigated by
      immunohistochemistry in bones of animals killed 3, 5, or 15 days after the
      initiation of daily loading. In animals killed at 3 or 5 days, periosteal
      surfaces undergoing load-induced reversal from resorption to formation showed
      enhanced tenascin-C staining. In animals killed at 15 days, the bone formed in
      response to loading was clearly demarcated from old bone by strong tenascin-C
      staining of reversal lines. Within this new bone, tenascin-C staining was seen in
      the lacunae of older but not more recently embedded osteocytes. The results
      presented here indicate that tenascin-C expression by bone cells is enhanced in
      the early osteogenic response to loading. This may indicate that tenascin-C acts
      as a mediator of the mechanically adaptive response.

PMID- 9240726
TI  - Biochemical markers of bone resorption compared with estimates of bone resorption
      from radiotracer kinetic studies in osteoporosis.
AB  - The pyridinium cross-links of collagen pyridinoline (Pyd) and deoxypyridinoline
      (Dpd) are released during bone resorption and are neither metabolized nor
      absorbed from the diet. The aim of this study was to validate their use in
      osteoporosis. We studied 19 women with osteoporosis and estimated the bone
      resorption rate from a combined calcium balance/kinetics technique without (R)
      and with partial (R(H)) and "complete" (Res) correction for long-term exchange.
      The strongest correlation was observed between the bone-specific marker (Dpd) and
      with complete correction for long-term exchange (Res) (r = 0.71, p < 0.001). The
      intercept was not different from zero, suggesting that bone was the major source
      for Dpd. The crude ratio of Dpd to Res in the 19 women was 54.5; but the
      regression coefficient relating Dpd as the dependent variable to Res was 31.8
      (95% CI 15.6-48.0), which was higher, but not significantly, than the ratio
      between Dpd and calcium (16.4) in 10 bone samples (cortical and trabecular bone).
      The weakest correlations between a biochemical marker and a kinetic index were
      those between hydroxyproline (a nonspecific marker of bone resorption) and R or
      R(H). Treatment with hormone replacement therapy (HRT) or HRT and parathyroid
      hormone peptide 1-38 in seven women over 1 year resulted in similar percent
      changes in the biochemical markers and estimates of bone resorption. We conclude
      that the measurement of Dpd provides a reasonably accurate assessment of bone
      resorption in osteoporosis, and in the context of several repeat 24-h collections
      of urine offers measurement precision that is similar to that obtainable with
      methods depending on the use of radioisotopic tracers and the assessment of
      metabolic calcium balance.

PMID- 9240727
TI  - Pooling of clodronate urinary excretion data: a new pharmacokinetic method to
      study drugs with highly variable gastrointestinal absorption.
AB  - Gastrointestinal absorption of bisphosphonates is highly variable from individual
      to individual (between-subject variation) and from day to day (within-subject
      variation), a fact that creates problems both in research and in clinical use of
      these drugs. We conducted a randomized, two-period cross-over pharmacokinetic
      (phase I) study to assess the relative bioavailability of two different
      clodronate preparations: an 800 mg tablet and a 400 mg capsule. Urinary excretion
      of clodronate correlates with gastrointestinal absorption. To minimize the
      confounding effect of the high variability of gastrointestinal absorption, we
      chose as the primary parameter the cumulative amount of clodronate excreted into
      urine (A(e0-t)) during 9 days (7 days of treatment, 2 days of follow-up). The 90%
      confidence interval calculated for the population medians of A(e0-t) was 0.83
      1.09, well within the 90% confidence interval stipulated for bioequivalence for
      the area under the curve values (0.80-1.25). This new procedure for pooling
      urinary excretion data offered a clear advantage over previous methods, and thus
      could presumably be used to study other drugs as well that are not metabolized
      and may show highly variable gastrointestinal absorption.

PMID- 9240728
TI  - Skeletal integrity in men chronically treated with suppressive doses of L
      thyroxine.
AB  - We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward's
      triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L
      T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n =
      5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter
      (n = 3). Patients were followed at our institution and treated with the minimal
      amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of
      evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14
      men (41.2%). The mean daily dose of L-T4 was 172 +/- 6 microg, and the cumulative
      dose of L-T4 was 673 +/- 71 mg. We found no significant difference between
      patients and age- and weight-matched controls in BMD (g/cm2) at any site of
      measurement (lumbar spine 1.144 +/- 0.12 vs. 1.168 +/- 0.15; femoral neck 0.979
      +/- 0.13 vs. 1.001 +/- 0.13; Ward's triangle 0.854 +/- 0.17 vs. 0.887 +/- 0.15;
      and trocanther 0.852 +/- 0.13 vs. 0.861 +/- 0.13). BMD was not correlated with
      the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of
      free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and
      osteocalcin were slightly but significantly elevated in patients compared with
      controls, whereas there was no difference in intact parathyroid hormone, bone
      alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone
      action). Our data suggest that L-T4 suppressive therapy, if carefully carried out
      and monitored, using the smallest dose necessary to suppress TSH secretion, has
      no significant effects on bone metabolism and bone mass in men.

PMID- 9240729
TI  - Is skeletal responsiveness to thyroid hormone altered in primary osteoporosis or
      following estrogen replacement therapy?
AB  - Hyperthyroidism is characterized by increased bone turnover and resorptive
      activity. Similar changes in remodeling are seen in osteoporosis. To study the
      pathogenetic role of thyroid hormone in osteoporosis, we measured concentrations
      of free and total thyroid hormones and investigated the sensitivity of the
      skeleton toward thyroid hormones in 14 osteoporotic, 16 estrogen-treated, and 15
      normal postmenopausal women with comparable thyroid status. Triiodothyronine (T3,
      60 microg/day for 7 days) was administered to the three groups. The skeletal
      response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin
      (BGP), and pyridinium cross-linked telopeptide domain of type I collagen (ICTP)
      in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and
      deoxypyridinoline (DPR) at days 0, 8, 15, and 57. Women on estrogen replacement
      therapy exhibited lower bone turnover than the normal postmenopausal women.
      Markers of bone formation were reduced by 19-43% and markers of resorption by 22
      48%. The osteoporotic women displayed lower bone mass at the lumbar spine and the
      distal forearm (p < 0.01-0.001), but the levels of biochemical markers of bone
      formation and resorption were comparable to values obtained in the normal
      postmenopausal women. T3 stimulation caused significant increases (p values
      ranging between 0.05-0.001) in all three groups of the resorptive markers: ICTP
      (47%, 47%, 45%), OHP (29%, 30%, 33%), PYR (43%, 27%, 51%), and DPR (42%, 24%,
      59%). Of the formative markers, only BGP increased significantly (32%, 40%, 47%)
      (p < 0.001). At day 57, however, all three formative markers increased compared
      with day 15 (p < 0.05-0.001). No significant differences in bone markers were
      demonstrated between groups. In the osteoporotic group, as the only group, serum
      calcium increased (p < 0.05) and serum PTH fell (p < 0.05). In conclusion,
      osteoporosis and estrogen substitution are not characterized by altered
      concentrations of thyroid hormones or responsiveness to thyroid hormones at the
      level of individual bone cells; however, altered responses pertaining to PTH and
      calcium were detected.

PMID- 9240730
TI  - The thickness of human vertebral cortical bone and its changes in aging and
      osteoporosis: a histomorphometric analysis of the complete spinal column from
      thirty-seven autopsy specimens.
AB  - The object of this study was to analyze the cortical thickness (Ct.Th) of the
      ventral and dorsal shell of the vertebral bodies throughout the human spine in
      aging and in osteoporosis. Therefore, the complete front column of the spine of
      26 autopsy cases (aged 17-90, mean 42 years) without diseases affecting the
      skeleton and of 11 cases (aged 58-92, mean 77 years) with proven osteoporosis
      were removed. A sagittal segment prepared through the center of all vertebral
      bodies was undecalcified, embedded in plastic, ground to a 1 mm thick block, and
      stained using a modification of the von Kossa method. The analysis included the
      measurement of the mean cortical thickness of both the ventral and dorsal shell,
      respectively (from the third cervical to the fifth lumbar vertebral body). The
      qualitative investigation of the structure of the cortical ring completed the
      analysis. The presented data revealed a biphasic curve for both the ventral and
      dorsal shell, skeletally intact with high values of the cortical thickness in the
      cervical spine (285 microm), and a decrease in the thoracic (244 microm) and an
      increase in the lumbar spine (290 microm). The mean thickness of the ventral
      shell is in general greater than the thickness of the dorsal shell in both
      skeletally normal and osteoporotic cases. The cortical thickness of the spine
      showed no gender-specific differences (p = NS). There was a slight decrease of
      the cortical thickness with aging; however, this decrease and the correlation of
      cortical thickness to age was only significant below vertebral body T8 (r = 0.225
      0.574; p(r) < 0.05-0.005). Most interestingly, however, osteoporosis presents
      itself with a highly significant loss of cortical thickness throughout the whole
      spine. This decrease of cortical thickness was more marked in the dorsal shell (p
      < 0.05) than in the ventral shell (ventral from C3 to T6 [p < 0.05] below T6 [p =
      NS]). We therefore conclude that in osteoporosis the loss of spinal bone mass is
      not only a loss of trabecular structure but also a loss of cortical thickness.
      Furthermore, these results may explain the development of regions of least
      resistance within the spine in aging and the clustering of osteoporotic fractures
      in the lower thoracic and lumbar spine.

PMID- 9240731
TI  - Localization and quantification of proliferating cells during rat fracture
      repair: detection of proliferating cell nuclear antigen by immunohistochemistry.
AB  - Bilateral femurs of 12-week-old female Sprague-Dawley rats were fractured, and
      the fractured femurs were harvested 36 h, 3, 7, 10, and 14 days after the
      fracture. Localization of cell proliferation in the fracture calluses was
      investigated using immunohistochemistry with antiproliferating cell nuclear
      antigen (PCNA) monoclonal antibodies. Thirty-six hours after the fracture, many
      PCNA-positive cells were observed in the whole callus. The change was not limited
      to mesenchymal cells at the fracture site where the inflammatory reaction had
      occurred, but extended in the periosteum along almost the entire femoral
      diaphysis where intramembranous ossification was initiated. On day 3, periosteal
      cells or premature osteoblasts in the newly formed trabecular bone during
      intramembranous ossification still displayed intense staining. On day 7, many
      premature chondrocytes and proliferating chondrocytes were PCNA positive.
      Endochondral ossification appeared on days 10 and 14, and the premature
      osteoblasts and endothelial cells in the endochondral ossification front were
      stained with anti-PCNA antibodies. Quantification of PCNA-positive cells was
      carried out using an image analysis computer system, obtaining a PCNA score for
      each cellular event. The highest score was observed in the periosteum early after
      the fracture near the fracture site. Immunohistochemistry using anti-PCNA
      antibodies showed that the distribution of proliferating cells and the degree of
      cell proliferation varied according to the time lag after the fracture,
      suggesting the existence of local regulatory factors such as growth factors, and
      that significant cell proliferation was observed at the beginning of each
      cellular event.

PMID- 9240732
TI  - Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss.
AB  - This study was performed to test the efficacy of short-term intravenous
      clodronate and etidronate in the prevention of postmenopausal bone loss. Healthy
      postmenopausal women, exhibiting a decreasing trend in bone mineral density, were
      randomized to five groups (clodronate at doses of 150, 300, and 600 mg;
      etidronate at a dose of 300 mg; and a placebo group) of 21-22 subjects. The drugs
      were administered intravenously three times with 1-week intervals, followed by
      regular evaluation for up to 24 months. During the first year, 300 mg of
      clodronate retarded bone loss significantly in the lumbar spine and femoral neck,
      where significant protection still persisted after 24 months. Other doses of
      clodronate (150 and 600 mg) were not bone protective. Etidronate (300 mg)
      retarded bone loss significantly in the lumbar spine up to 24 months, relative to
      placebo. Serum concentrations of procollagen I carboxy-terminal propeptide and
      urinary Ca2+ and hydroxyproline excretion decreased in all bisphosphonate groups
      during the first month after treatment, but the values returned later toward
      baseline. In the etidronate-group, serum osteocalcin concentrations also
      decreased significantly during the first 3 months of the study. Otherwise, no
      uniform serum responses to bisphosphonate-treatment were detected in circulating
      markers of bone formation, alkaline phosphatase, or osteocalcin. No significant
      differences in the serum concentrations of cross-linked carboxy-terminal
      telopeptide of type I collagen were detected between the groups. Patient
      acceptance of both bisphosphonates was excellent, and no drug-related adverse
      side effects were detected. These results suggest that infrequently repeated
      intravenous treatment with bisphosphonates may effectively counteract
      postmenopausal bone loss.

PMID- 9240733
TI  - Correlation of trabecular bone structure with age, bone mineral density, and
      osteoporotic status: in vivo studies in the distal radius using high resolution
      magnetic resonance imaging.
AB  - High resolution magnetic resonance (MR) images of the distal radius were obtained
      at 1.5 Tesla in premenopausal normal, postmenopausal normal, and postmenopausal
      osteoporotic women. The image resolution was 156 microm in plane and 700 microm
      in the slice direction; the total imaging time was approximately 16 minutes. An
      intensity-based thresholding technique was used to segment the images into
      trabecular bone and marrow, respectively. Extensions of standard stereological
      techniques were used to derive measures of trabecular bone structure from these
      segmented images. The parameters calculated included apparent measures of
      trabecular bone volume fraction, trabecular thickness, trabecular spacing, and
      trabecular number. Fractal-based texture parameters, such as the box-counting
      dimension, were also derived. Trabecular bone mineral density (BMD) and cortical
      bone mineral content (BMC) were measured in the distal radius using peripheral
      quantitative computed tomography (pQCT). In a subset of patients, spinal
      trabecular BMD was measured using quantitative computed tomography (QCT).
      Correlations between the indices of trabecular bone structure measured from these
      high-resolution MR images, age, BMD, and osteoporotic fracture status were
      examined. Cortical BMC and trabecular BMD at the distal radius, spinal BMD,
      trabecular bone volume fraction, trabecular thickness, trabecular number, and
      fractal dimension all decreased with age. Trabecular spacing showed the greatest
      percentage change and increased with age. In addition, significant differences
      were evident in spinal BMD, radial trabecular BMD, trabecular bone volume
      fraction, trabecular spacing, and trabecular number between the postmenopausal
      nonfracture and the postmenopausal osteoporotic subjects. Trabecular spacing and
      trabecular number showed moderate correlation with radial trabecular BMD but
      correlated poorly with radial cortical BMC. High resolution MR imaging, a
      potentially useful tool for quantifying trabecular structure in vivo, may have
      applications for understanding and evaluating skeletal changes related to age and
      osteoporosis.

PMID- 9240734
TI  - Correcting the magnification error of fan beam densitometers.
AB  - Dual-energy X-ray absorptiometry (DXA), using a narrow pencil-shaped X-ray beam
      coupled to a single detector, has been used extensively. More recently, DXA using
      a fan- shaped X-ray beam coupled to an array of detectors has been introduced.
      This new generation of scanners causes an inherent magnification of scanned
      structures as the distance from the X-ray source decreases. This magnification,
      which occurs in the medial-lateral direction but not in the craniocaudal
      direction, does not affect bone mineral density (BMD). There are, however,
      significant changes of bone mineral content (BMC), bone area, and parameters of
      hip geometry, with varying distance of the bone scanned from the X-ray source.
      Variability of soft tissue thickness in vivo, by altering the distance of the
      skeleton from the scanning table and X-ray source, may cause clinically
      significant errors of BMC, bone area, and proximal femur geometry when measured
      using fan-beam densitometers. We analyzed the geometry of Lunar and Hologic fan
      beam scanners to derive equations expressing the true width of scanned structures
      in terms of the apparent width and machine dimensions. We also showed mathematic
      ally that performing an additional scan, at a different distance from the X-ray
      source than the first scan, provides simultaneous equations that can be solved to
      derive the real width of a scanned bone. This hypothesis was tested on the Lunar
      Expert using aluminium phantoms scanned at different table heights. There was an
      excellent correlation, r = 0.99 (p < 0.001), between the predicted phantom width
      and the measured phantom width. In conclusion, this study shows that the
      magnification error of fan beam DXA can be corrected using a dual scanning
      technique. This has important implications in the clinical usefulness of BMC and
      geometrical measurements obtained from these scanners.

PMID- 9240735
TI  - Sources of variability in bone mineral density measurements: implications for
      study design and analysis of bone loss.
AB  - Measurement of bone mineral density (BMD) is a useful tool for monitoring
      efficacy in osteoporosis therapy. However, the ability to detect true change for
      a subject as well as for a group of subjects is dependent on the precision of the
      measurement. In this paper, short-term and long-term reliability of bone mass
      measurements were examined at the spine and femoral neck using dual-photon and
      dual-energy X-ray absorptiometry and related to guidelines for study design. The
      concepts involved in these analyses are relevant to a study for any therapy
      involving a quantitative trait. Short-term reliability was assessed by repeated
      measures in 60 subjects aged 46 +/- 9 years (mean +/- standard deviation [SD]),
      and in 32 elderly subjects (aged 75 +/- 5 years), on the same day with
      repositioning. Long-term variability in the rate of linear changes in BMD was
      assessed in a cohort of 293 women and 184 men, aged 60+, each having BMD measured
      on three separate occasions over an average interval of 2 years. Short-term
      variability in BMD was assessed using the coefficient of reliability (R) and
      standard deviation (SD) of measurement error. Long-term variability in BMD was
      modeled by linear regression. In the younger sample, the SD of measurement error
      for the lumbar spine and femoral neck was 14 and 25 mg/cm2, respectively,
      yielding coefficients of reliability for short-term measurements of 0.99 and
      0.97, respectively. In the elderly sample, the coefficient of reliability was
      0.96 and 0.77 for lumbar spine and femoral neck, respectively. For long-term
      variability, for which a linear rate of change in BMD was assumed, the SD of
      intrasubject variation in the women was 42 mg/cm2 at both the lumbar spine and
      femoral neck and in men 57 and 42 mg/cm2, respectively. The between-subject SD of
      the rates of change was higher in males than females (21 and 14 mg/cm2/year,
      respectively; p = 0.037). Importantly, intrasubject estimation error contributed
      about 90% of the variability component. These sources of variability lead to
      reduction in the power of a study and underestimation of the relative risk in
      logistic regression relating BMD and fracture risk in population studies. At the
      individual level, they increase the false-positive and false-negative error rates
      of diagnostic BMD and present major difficulties in the assessment of bone loss.
      The measurement error can be reduced by taking multiple measurements per visit.
      However, long-term intrasubject variation can be reduced by increasing the length
      of follow-up and/or increasing the frequency of measurements and, in a study, by
      increasing the number of subjects. Modeling of these errors, study duration, and
      frequency of measurements indicates that studies with a duration of 3-5 years
      appear to have the optimum "cost-benefit," and making measurements more than
      twice a year does not improve the precision appreciably. These modeling
      approaches can be extended to other clinical studies involving quantitative
      measurements with measureable errors within and between individuals and
      contributes to rational selection of the duration and frequency of measurements.

PMID- 9240736
TI  - A preliminary evaluation of the lunar expert-XL for bone densitometry and
      vertebral morphometry.
AB  - We have evaluated the Lunar Expert-XL for standard bone mineral densitometry
      (BMD) and for morphometric imaging of the spine in the lateral projection. The
      short-term precision in vitro of the Expert-XL for BMD measurements was 0.7% for
      the Hologic and European spine phantoms, and the long-term stability (15-month)
      measurements had a 1.1% coefficient of variation. The precision in vivo for three
      operators examining a group of 10 premenopausal women was 0.9-1.5% for lumbar
      spine (L2-L4), 1.7-2.2% for the femoral neck, and 0.9% for the total hip region
      of interest. For a group of nine postmenopausal women, the lumbar spine, femoral
      neck, and total femur precision ranges were 2.0-2.4, 1.2-2.9, and 1.6-1.7%
      respectively. For L2-L4, BMD comparison between the Expert-XL and DPX-L yielded a
      correlation coefficient of r = 0.98, a slope of 0.86, and an intercept of 0.139
      g/cm2. The femoral neck results were r = 0.92, slope = 1.00, and intercept = 0.03
      g/cm2. In an evaluation of the Expert-XL for lateral morphometry, we employed a
      group of 16 postmenopausal women. Comparison of vertebral dimensions between the
      Expert-XL and radiographic morphometry showed strong agreement (r = 0.97), but
      the interobserver variability for vertebral height was higher for the Expert-XL
      than for radiographs (3-5% vs. 1-2%). In a subset of four women who had repeat
      scans, the interscan precision for measuring vertebral dimensions was 1.9, 4.1,
      and 43% for the L1-L4, T12-T8, and T7-T5 levels respectively. In the Expert-XL
      images, it was possible to identify clearly L4-T4 in 10 of 16 patients and L4-T6
      in 15 of 16, indicating potential utility for vertebral fracture prescreening.

PMID- 9240737
TI  - Fat or lean tissue mass: which one is the major determinant of bone mineral mass
      in healthy postmenopausal women?
AB  - The relative importance of fat and lean tissue mass in determining bone mineral
      mass among postmenopausal women was examined in this 1-year longitudinal study.
      Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1
      year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total
      and regional bone mineral density (BMD) and bone mineral content (BMC), fat
      tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear
      regression analysis using the cross-sectional data (n = 50) of the study
      indicated that LTM explained a larger percentage of variation in bone mineral
      mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55);
      when FTM was entered in the same predicting regression models, LTM was a
      significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The
      percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant
      correlation was primarily found only for total body BMD (or BMC). Weight was the
      best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes
      in both FTM and weight were significantly associated with annual changes in
      regional BMD after adjustment for initial bone mineral values (p < 0.05). We
      conclude that bone mineral mass is more closely related to LTM than to FTM, while
      annual changes in regional BMD are more closely correlated with changes in FTM in
      healthy postmenopausal women. Meanwhile, increased body weight is significantly
      associated with increased bone mineral mass.

PMID- 9240738
TI  - Vertebral deformities and functional impairment in men and women.
AB  - The objective of this study was to assess the prevalence and health effects of
      vertebral deformities in men and women. The study was carried out as part of the
      cross-sectional baseline phase of The Rotterdam Study, a prospective population
      based cohort study of residents aged 55 years or over of a district of Rotterdam,
      The Netherlands. The prevalence of vertebral deformities according to a
      modification of the Eastell method and concomitant functional impairment were
      assessed in a random sample of 750 men and 750 women. The prevalence of moderate
      (grade I) vertebral deformities was 8 and 7% in men and women, respectively. For
      severe deformities (grade II), these percentages were 4 and 8%. In men, the
      prevalence of both moderate and severe deformities increased with age. In women,
      however, the prevalence of moderate vertebral deformities remained constant,
      opposite to a marked increase in severe deformities. Moderate vertebral deformity
      was significantly associated with impaired rising in men only. Severe vertebral
      deformity was associated with a significantly increased risk of general
      disability and the use of a walking aid in both men and women, impaired bending
      in men, and impaired rising in women. It is concluded that (1) vertebral
      deformities are only slightly less common in men than in women from the general
      population and (2) severe progression with age occurs in women only and (3)
      severe vertebral deformity is, particularly in men, related to functional
      impairment.

PMID- 9240739
TI  - Code of ethical principles for genetics professionals.

PMID- 9240740
TI  - Code of ethical principles for genetics professionals: an explication.

PMID- 9240741
TI  - Gaucher disease: functional expression of the normal glucocerebrosidase and
      Gaucher T1366G and G1604A alleles in Baculovirus-transfected Spodoptera
      frugiperda cells.
AB  - Gaucher disease is an inherited sphingolipidosis resulting from deficient
      glucocerebrosidase activity. Three clinical forms of Gaucher disease have been
      described: type 1 as non-neuronopathic, type 2 as acute neuronopathic, and type 3
      as subacute neuronopathic. We recently identified a rare mutation (G-->A at
      glucocerebrosidase cDNA nucleotide position 1604) [Choy et al., 1994a, Am J Med
      Genet 51:156-160] and a novel mutation (T-->G at glucocerebrosidase cDNA
      nucleotide position 1366) in two type 1 Gaucher patients by sequence analysis of
      the entire glucocerebrosidase coding region [Choy et al., 1994a, 1994b, Hum Mol
      Genet 3:821-823]. To demonstrate that these are deleterious and not neutral
      mutations, we cloned the full-length glucocerebrosidase cDNA of patients and of a
      normal control in the plasmid vector pAcUW1, recombined the human gene into the
      Baculovirus genome downstream of its polyhedron p10 promoter, and expressed the
      inserted gene in cultured cells of Spodoptera frugiperda transfected by
      recombinant Baculovirus. The levels of residual glucocerebrosidase activity
      determined in transfected cells with the Gaucher G1604A and T1366G alleles are
      6.9% and 2.9% of that expressed by the normal allele (normal = 352.0 nmol/hr/mg
      protein or 100%). By comparison, the enzyme-specific activity expressed in
      transfected cells by 2 known Gaucher alleles, A1226G and T1448C, that are
      prevalent in type 1 and type 2 Gaucher disease are 23.4% and 3.3% of normal. No
      endogeneous glucocerebrosidase activity was detected in cultured cells
      transfected by either the wild-type Baculovirus or Baculovirus with the pAcUW1
      plasmid vector without the glucocerebrosidase cDNA insert. These findings show
      that the Baculovirus expression system in cultured Spodoptera frugiperda cells is
      a suitable system for the functional expression and characterization of the
      normal and mutant glucocerebrosidase alleles. Moreover, the use of this
      expression system demonstrates that the G1604A and T1366G mutations are both
      deleterious mutations resulting in profoundly deficient glucocerebrosidase
      activity and subsequent Gaucher disease.

PMID- 9240743
TI  - Trisomy 10p: report of an unusual mechanism of formation and critical evaluation
      of the clinical phenotype.
AB  - A de novo tandem inverted duplication of 10p was diagnosed in a 17-week fetus.
      The appearance of GTG banded preparations and the results of fluorescence in situ
      hybridization (FISH) studies are consistent with duplication of the entire arm,
      including the telomere. The FISH studies also demonstrated the presence of
      chromosome 10 alphoid repeats at the junction between the inverted segment and
      the long arm, consistent with the presence of the entire long arm of the abnormal
      chromosome. Therefore, this is a case of pure trisomy 10p without an associated
      deficiency of any other chromosome segment. A comparison of the phenotype
      associated with pure trisomy 10p and trisomy associated with a
      duplication/deficiency state documented a higher frequency (of borderline
      significance) of clubfoot and high-arched/cleft palate in the cases of pure
      trisomy. The frequency of palatal anomalies was observed to be significantly
      higher in the cases where the breakpoint of the trisomic segment is in the most
      proximal band (10p11). However, other clinical manifestations were observed
      inconsistently, even in the cases with pure, nearly complete trisomy 10p.
      Therefore, a clearly defined trisomy 10p clinical syndrome could not be
      documented in this study.

PMID- 9240742
TI  - Toward quality assurance for metaphase FISH: a multicenter experience.
AB  - Although fluorescent in situ hybridization (FISH) is rapidly becoming a part of
      clinical cytogenetics, no organization sponsors multicenter determinations of the
      efficacy of probes. We report on 23 laboratories that volunteered to provide
      slides and to use a probe for small nuclear ribonucleoprotein polypeptide N
      (SNRPN) and a control locus. Experiences with FISH for these laboratories during
      1994 ranged from 0 to 645 utilizations (median = 84) involving blood, amniotic
      fluid, and bone marrow. In an initial study of hybridization efficiency, the
      median percentage of metaphases from normal individuals showing two SNRPN and two
      control signals for slides prepared at each site was 97.0 (range = 74-100); for
      slides prepared by a central laboratory, it was 97.8 (range = 81.6-100). In a
      subsequent blind study, each laboratory attempted to score 5 metaphases from each
      of 23 specimens [8 with del(15)(q11.2-->q12) and 15 with normal #15 chromosomes].
      Of 529 challenges, the correct SNRPN pattern was found in 5 of 5 metaphases in
      457 (86%) and in 4 of 5 in 33 (6%). Ambiguous, incomplete, or no results were
      reported for 32 (6%) challenges. Seven (1%) diagnostic errors were made,
      including 6 false positives and 1 false negative: 1 laboratory made 3 errors, 1
      made 2, and 2 made 1 each. Most errors and inconsistencies seemed due to
      inexperience with FISH. The working time to process and analyze slides singly
      averaged 49.5 min; slides processed in batches of 4 and analyzed singly required
      36.9 min. We conclude that proficiency testing for FISH by using an extensive
      array of challenges is possible and that multiple centers can collaborate to test
      probes and to evaluate costs.

PMID- 9240745
TI  - Plasma hyaluronidase activity in mucolipidoses II and III: marked differences
      from other lysosomal enzymes.
AB  - A nearly pathognomonic finding of the lysosomal storage disorders mucolipidoses
      II and III is the marked increase of plasma lysosomal enzyme activities. The
      genetic lesion in ML II and III causes defective function of the enzyme UDP
      GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. Defective
      function of this enzyme results in deficient phosphorylation of lysosomal enzyme
      asparagine-linked oligosaccharides and a consequent misrouting of many newly
      synthesized lysosomal enzymes. These enzymes are secreted from cells instead of
      being targeted to lysosomes, with resultant marked elevations of multiple
      lysosomal enzyme activities in plasma. We report here that plasma hyaluronidase
      activity, an endoglycosidase of presumably lysosomal origin, is not increased in
      the plasma from individuals with mucolipidoses II and III, unlike most lysosomal
      enzymes. Our data suggest the possibility that hyaluronidase is not targeted to
      lysosomes by a lysosomal enzyme phosphosmannosyl recognition mechanism.
      Alternatively, hyaluronidase activity may not be present in the cell type(s)
      responsible for the lysosomal enzyme hypersecretion in mucolipidoses II and III
      which, along with its deficiency in fibroblasts and leukocytes, would constitute
      an unusual tissue distribution of activity for a soluble lysosomal enzyme.

PMID- 9240744
TI  - Fibrotic eye muscles, Axenfeld anomaly, flat face, and mild developmental
      retardation: a new example of the Chitty syndrome.
AB  - We have studied a girl with fibrotic extrinsic eye muscles, Axenfeld anomaly,
      unusual facial appearance, mild hydrocephaly, and neurodevelopmental delay. Her
      condition is similar to the one described recently in members of a single family
      by Chitty et al. [1991, Am J Med Genet 40:417-420]. We suggest that she
      represents a second example of what may be called the Chitty syndrome.

PMID- 9240746
TI  - Autosomal dominant familial radial luxation, carpal fusion and scapular dysplasia
      with variable heart defects.
AB  - A family is described with skeletal abnormalities involving the shoulder, elbow,
      and hand, in combination with variable cardiac defects including conduction
      defects and anatomical anomalies. The disorder followed an autosomal dominant
      pattern of inheritance with apparently full penetrance for the skeletal
      abnormalities and reduced penetrance for the cardiac defects.

PMID- 9240747
TI  - Evidence for a critical region for penoscrotal inversion, hypospadias, and
      imperforate anus within chromosomal region 13q32.2q34.
AB  - Two unrelated patients with small distal deletions of the long arm of chromosome
      13 are described, with shawl scrotum and penoscrotal transposition, penoscrotal
      hypospadias, a reduced perineum, and anal atresia. The patients have small
      deletions of 13(q32.2qter) and 13(q32q34), respectively. This report and the
      literature present evidence for one or possibly more gene(s) within region
      13q32.2q34 which regulate the development of the ano-genital structures. The
      clinical spectrum includes bifid or shawl scrotum, hypospadias, biseptate uterus,
      malplaced and imperforate anus, and common cloaca.

PMID- 9240748
TI  - Possibly new multiple congenital anomaly syndrome: cranio-fronto-nasal dysplasia
      with Poland anomaly.
AB  - We present a possibly new multiple congenital anomaly syndrome of
      craniosynostosis, Poland anomaly, cranio-fronto-nasal "dysplasia," and genital
      and breast anomalies. A similar pattern of anomalies was observed in two previous
      cases from the literature; however, some peculiar findings suggest that these
      cases might represent a new multiple congenital anomaly syndrome.

PMID- 9240749
TI  - Segregation analysis of microcephaly.
AB  - Microcephaly is a heterogeneous disorder with genetic and environmental causes.
      However, there is little information on what proportion of cases are caused by
      inherited susceptibility, or the mode of inheritance in familial cases. To
      address these questions, we have performed classical and complex segregation
      analyses for microcephaly on 2 sets of family data collected from genetic
      counseling clinics in Vancouver and Jerusalem. These samples consisted of 143
      affected individuals in 127 families ascertained from Vancouver, and 101 affected
      individuals in 59 families ascertained from Jerusalem. The results of the
      segregation analyses for the Vancouver sample indicated that approximately half
      of all microcephaly cases were due to highly penetrant recessive mutant alleles,
      with the remainder being sporadic. Although a recessive model allowing for the
      occurrence of sporadic cases fit the data from Vancouver best, a dominant model
      could not be statistically rejected. The classical segregation analysis on the
      Jerusalem sample suggested that both a dominant model with 29% of the cases being
      sporadic and a purely recessive model provided adequate fit to the data. Although
      the complex segregation analysis of this sample indicated that a dominant model
      provided a more parsimonious explanation for the observed familial variation, a
      recessive model was only marginally rejected. It should be noted that in the
      Jerusalem sample, families tended to be ascertained in the genetic counseling
      clinic only after the birth of a second affected child. This could be a potential
      bias which could inflate the segregation ratio, thus giving the impression of
      dominant inheritance. Our analyses, while confirming the complex nature of the
      cause of microcephaly, indicate that it may be necessary to await the results of
      genetic linkage analysis before a definitive mode of inheritance can be
      determined.

PMID- 9240750
TI  - Association of professors of human or medical genetics: summary of first annual
      workshop.

PMID- 9240751
TI  - Hereditary deficiency of vitamin K-dependent coagulation factors with skeletal
      abnormalities.
AB  - We describe a female infant who presented with severe intracranial bleeding and
      was found to have a hereditary deficiency of vitamin K-dependent coagulation
      factors. She also had mild stippling of the left femoral epiphysis and shortness
      of the distal phalanges of the fingers. We studied the possible relationship
      between these abnormalities and a peroxisomal defect and followed their responses
      to treatment with vitamin K. The level of vitamin K-dependent clotting factors
      returned to near-normal following treatment with pharmacological doses of vitamin
      K, but there was no effect on the skeletal abnormalities.

PMID- 9240752
TI  - Trisomy 17 detected in amniotic fluid cells but not in newborn infant.

PMID- 9240753
TI  - Propositus with Weaver syndrome and his mildly-affected mother: implication of
      nontraditional inheritance?

PMID- 9240754
TI  - GAPO syndrome in Turkiye.

PMID- 9240755
TI  - Insulin resistance and hypertension in Japanese.
AB  - In this article, some of our findings of epidemiologic and clinical studies on
      the actual state of insulin resistance in hypertension occurring in Japanese were
      described. In epidemiologic studies, a high prevalence of concomitant
      hypertension and impaired glucose tolerance was observed, and a significant
      positive correlation was found between blood pressure and blood glucose levels,
      even at a low degree, in two towns, the agricultural districts of Hokkaido. In
      clinical studies, insulin sensitivity, which was measured as M-values by the
      euglycemic hyperinsulinemic glucose clamp method, was significantly lower in
      essential hypertensives than in normotensive subjects. Moreover, this suppression
      of insulin sensitivity was also observed in young normotensive subjects with an
      apparent family history of hypertension, preceding the manifestation of
      hypertension. At the same time, obesity and aging were definitely correlated to
      the decrease in insulin sensitivity. On the assumed criterion that the normal
      range of M-values is mean +/- 1 SD of non-obese, non-diabetic young normotensive
      subjects, the prevalence of individuals with lowered M-value, which means
      existence of insulin resistance, was calculated as 45.4% in essential
      hypertensives and as 16.3% in normotensive subjects in this study. Increases in
      plasma norepinephrine levels and plasma renin activity, and decreases in urinary
      excretion of sodium and fractional excretion of sodium were observed during
      hyperinsulinemia produced by glucose clamp test. These responses to
      hyperinsulinemia were not different from those in normotensive subjects and,
      therefore, not specific to essential hypertensives. From these results, it was
      concluded that insulin resistance definitely exists among Japanese essential
      hypertensives, and that it plays an important role in the pathophysiology of
      essential hypertension.

PMID- 9240756
TI  - The deadly quartet and the insulin resistance syndrome: an historical overview.
AB  - Since the original observations by Vague almost 50 years ago, a massive
      literature has documented the pathological consequences of upper body or visceral
      obesity. These consequences likely relate to the presence of hyperinsulinemia.
      More recently, the presence of hyperinsulinemia has also been recognized in
      nonobese hypertensives as a feature of the insulin resistance syndrome. This
      paper will provide an historical overview of the two clinical syndromes.

PMID- 9240757
TI  - Insulin and cardiovascular diseases in Japanese work-site population with
      borderline to mild hypertension.
AB  - To clarify whether significant interrelations between hyperinsulinemia and
      cardiovascular diseases exist in Japanese, we analyzed serum insulin levels,
      fasting and after oral glucose load, in relation to blood pressure (BP), serum
      lipids, and incidence of acute myocardial infarction (MI) and stroke in 584 male
      employees of a railroad company with borderline to mild hypertension (age: 49 +/-
      7 years, BP: 139 +/-13/90 +/- 8 mmHg, body mass index: BMI 24.0 +/- 2.8, mean +/-
      SD). Those who were taking antihypertensive drugs and/or hypoglycemic agents were
      excluded. The subjects were classified into five groups of comparable size
      according to sigma IRI (area composed by insulin levels at 0, 1, 2 hours post
      glucose load). Although averaged age, levels of fasting glucose and HbA1c were
      not significantly different among quintiles, the hyperinsulinemic groups had
      higher levels of fasting IRI and sigma glucose. Multiple regression analysis
      revealed that sigma IRI was associated positively with BMI, sigma glucose,
      systolic BP, total cholesterol, and negatively with HDL-cholesterol. During 7
      year follow-up 7 cases with MI and 15 cases with stroke were registered. The
      subjects with MI, but not with stroke were involved in higher deciles of insulin
      levels. These results indicate that the insulin resistance syndrome exists in
      Japanese middle-aged men with borderline to mild hypertension. The association
      with cardiovascular morbid events appeared to be evident in coronary heart
      disease but not in cerebrovascular disease.

PMID- 9240758
TI  - Insulin resistance syndrome in adolescents and adults.
AB  - This study was designed to investigate the possibility of sex and age differences
      in the insulin-blood pressure relationship in a general Japanese population with
      a wide age range. Fasting serum insulin, lipids, plasma glucose, blood pressure
      and anthropometric measurements were made on 1,537 men and 843 women aged 16 to
      65 years. Of the 2,380 subjects in the present analysis, 290 (184 men, 106 women)
      were hypertensive. When divided into four age groups (16 to 17, 21 to 22, 30 to
      49 and 50 to 65 years), the male hypertensive subjects were found to have
      significantly higher fasting insulin levels, triglycerides levels and body mass
      index and lower glucose/insulin ratios than normotensive male subjects in all age
      groups. In the women, there was no significant difference in serum insulin levels
      or glucose insulin ratios between the hypertensive and normotensive groups in any
      age group. Simple correlation analysis showed that blood pressure was
      statistically significantly correlated with serum insulin levels and body mass
      index in the men in all age groups. In women, the correlation between blood
      pressure and serum insulin was insignificant in the 21- to 22-year-old age group.
      In men but not women, multivariate analysis showed that blood pressure was
      significantly and independently correlated with fasting serum insulin levels. The
      results of this study suggests the existence of sex and age differences in the
      insulin-blood pressure relationship in a Japanese population.

PMID- 9240759
TI  - The effect of age on glucose tolerance and plasma insulin level in hypertensive
      and normotensive subjects.
AB  - To elucidate the effect of aging and blood pressure on glucose tolerance, we
      examined the subjects who received 75g OGTT annually for 10 years. They were
      classified into 2 groups by blood pressure, and into 4 groups by age. The study
      group consisted of 34 cases (mean 62 years old), including 11 hypertensive (HT)
      and 23 normotensive (NT) control. All cases had their body weight fluctuate in
      less than 4 kgs. After blood pressure was measured, blood was drawn for
      determination of plasma glucose and insulin concentrations in each subject before
      75g OGTT and 30, 60, 90, 120 minutes afterward. sigma BS and sigma IRI were
      defined as the sum of 5 points in BS and IRI, respectively. Insulinogenic index
      (I.I) was defined as deltaIRI/deltaBS in 30 min. sigma IRI/sigma BS and I.I of
      each year were calculated serially. They were compared between HT and NT group,
      and among 4 groups of age; 40s, 50s, 60s and 70s. sigma IRI/sigma BS was
      significantly decreased in both HT and NT groups (0.52 +/- 0.05 (mean +/- SE) to
      0.29 +/- 0.04; p <0.0001 vs. 0.42 +/- 0.05 to 0.23 +/- 0.02; p < 0.0001,
      respectively). But significant difference between the 2 groups was not observed.
      No significant difference of sigma IRI/sigma BS among 4 groups of age was found.
      There were significant differences between I.I of the first year and that of
      several years, but they did not correlate linearly. These data indicate that the
      effect of age on the diminution of sigma IRI/sigma BS was significant for 10
      years follow-up of the same subjects in both HT and NT groups. But there were no
      significant differences in classified groups by blood pressure and age.

PMID- 9240760
TI  - Insulin resistance, hypertension and nephropathy.
AB  - Although insulin resistance has been involved in the pathogenesis of essential
      hypertension in non-diabetic patients, few studies were performed regarding to
      the association between insulin resistance, hypertension and nephropathy in
      diabetes mellitus. We observed the changes of blood pressure and proteinuria for
      7 years in normotensive 28 patients with non-insulin-dependent diabetes mellitus
      (NIDDM), following measurement of insulin sensitivity. Patients were over 40
      years old and not obese, and fasting plasma glucose levels were less than 140
      mg/dl. Insulin sensitivity was determined using glucose-clamp method or glucose,
      insulin, and somatostatin infusion method. In 28 subjects, 12 subjects developed
      hypertension and 16 subjects were remained normotensive. Insulin induced glucose
      clearance was significantly decreased in subjects developed hypertension (30 +/-
      12 ml/kg/10 min) than in subjects remained normotensive (50 +/- 19 ml/kg/10 min).
      Furthermore, we found significantly higher incidence of proteinuria in patients
      developed hypertensive (7 out of 12 patient) than in patients remained
      normotensive (one out of 16 patients; p < 0.05). These results suggest that
      insulin resistance is involved in the etiology of hypertension in NIDDM patients,
      and that this derangement has an important role for the progression of diabetic
      nephropathy.

PMID- 9240762
TI  - Major risk factors for atherosclerosis are manifested in experimental Ca
      deficiency.
AB  - The eggshell is the major source of Ca required during growth of chick embryos.
      Therefore, chick embryos placed ex ovo for long-term (SL) are rendered severe
      systemic calcium deficiency. We report here that SL chick embryos express Ca
      deficiency related atherogenic disorders, and that in vitro Ca-deficiency induces
      dedifferentiation, i.e. loss of cell-type specific features and accelerated
      proliferative activities, in the various types of cultured cells. Systemic blood
      pressure is significantly higher and an accelerated weight gain of the heart is
      noted in SL compared to normal embryos (NL) at the incubation Day-14. Plasma
      cholesterol was lower, while triglyceride and glucose were higher in SL. Varying
      Ca in the culture medium (FCa, 1.8 mM; HCa, 2.8 mM; Ca/2, 0.9 mM) clearly
      affected the phenotype of the cultured cardiomyocytes and vascular cells isolated
      from the chick embryos. The cell number and total DNA were significantly larger
      and the level of LDH and proliferating cell nuclear antigen (PCNA) was elevated
      in Ca/2 compared to FCa. On the contrary, the level of CPK and contractile
      proteins were lowered in Ca/2. Thus, it is indicated that Ca-deficiency induces
      atherogenic disorders in vivo, and accelerates cell proliferation and decelerates
      sarcomeric protein expression in vitro. Taken together, it is suggested that the
      atherogenic, developmental disorders in SL may be the integrated result of the
      phenotype alteration in the various cell types directly induced by Ca-deficiency.

PMID- 9240761
TI  - Analysis of candidate genes for insulin resistance in essential hypertension.
AB  - To clarify the genetic basis of insulin resistance in hypertension, case-control
      association studies were performed to examine candidate genes for insulin
      resistance in hypertension. Since the main site of insulin resistance in
      hypertension is glycogen synthesis in skeletal muscle, genes that encode
      molecules involved in this pathway, i.e. insulin receptor (INSR), insulin
      responsive glucose transporter (GLUT4) and glycogen synthase (GSY), were studied.
      In addition, since recent studies suggest the contribution of beta3 adrenergic
      receptor to the insulin resistance syndrome, the gene encoding beta3 adrenergic
      receptor (ADRB3) was also studied. Frequency of homozygotes for common C allele
      of a microsatellite polymorphism in the INSR gene was higher in the
      hyperinsulinemia group, but not in the normoinsulinemia group of hypertensive
      patients than in normotensive control subjects. Insulin sensitivity, however, was
      not significantly different between hypertensive patients with C/C genotype and
      those without this genotype. No significant differences were observed in the
      distribution of alleles or genotypes of the GLUT4, GSY and ADRB3 genes between
      hyperinsulinemia and normoinsulinemia groups of hypertensive patients or between
      these groups and the control group. These data suggest that the INSR polymorphism
      is associated with hyperinsulinemia, but not with insulin resistance, in
      hypertension.

PMID- 9240763
TI  - Tubular effects of insulin.
AB  - The direct effect of insulin on NaCl transport in proximal tubules and thick
      ascending limbs of Henle's loop were examined. First, the effects of insulin on
      intracellular pH (pHi) in the in vitro microperfused rabbit S2 proximal straight
      tubules (PST) were examined using a fluorescent technique. Addition of insulin to
      the bath increased pHi in a dose-dependent manner at concentrations ranging from
      10(-11) to 10(-6) mol/l, and its ED50 was 10(-9) mol/l. The insulin-induced pHi
      increase was almost completely inhibited by 10(-3) mol/l amiloride in the lumen,
      indicating that insulin activates luminal Na/H exchange in PST. Next, the effect
      of insulin on the transepithelial voltage (Vt) and lumen-to-bath Cl flux (JCl)
      were examined in the in vitro microperfused rabbit medullary thick ascending
      limbs of Henle's loop (MTAL). Insulin in the bath increased Vt in a dose
      dependent manner, and its ED50 was 5 X 10(-9) mol/l. Insulin significantly
      increased JCl. The insulin-mediated increase in Vt was abolished by ouabain and
      furosemide. Dibutyryl-cAMP (dbcAMP) increased Vt and JCl. H-8 abolished the
      effect of dbcAMP, while it did not inhibit the actions of insulin. Removal of
      extracellular Ca did not affect the effects of insulin on Vt and JCl. Chelation
      of intracellular Ca with BAPTA/AM inhibited the actions of insulin without
      affecting basal values. Calmodulin (CaM) inhibitors, trifluoperazine and W-7,
      inhibited the actions of insulin more than 90%. These results indicate that
      insulin directly increases NaCl reabsorption in the MTAL, which requires the
      activation of Ca-CaM system, independent of the adenylate cyclase-cAMP-PKA
      system. In conclusion, insulin directly stimulates NaCl reabsorption in the in
      vitro microperfused rabbit PST and MTAL.

PMID- 9240764
TI  - Effects of intra-arterial infusion of insulin on control of forearm vascular
      resistance in normotensive and hypertensive subjects.
AB  - In this article, I will review the recent progress in the relationship between
      hyperinsulinemia and control of vascular resistance. I particularly focus on
      effects of intra-arterial infusion of insulin on control of resting forearm
      vascular resistance and on vascular reactivity to vasoconstrictor agents in
      normotensive and hypertensive subjects. In conclusion, the physiological levels
      of local hyperinsulinemia may decrease resting forearm vascular resistance in
      some normotensive subjects but not in all. Insulin-induced vasodilation may be
      due to the production of prostacyclin but not due to nitric oxide.
      Hyperinsulinemia attenuates vasoconstriction induced by phenylephrine and
      angiotensin II in normotensive subjects. Although acute intra-venous infusion of
      insulin activates the sympathetic nerve system, it may not elevate blood pressure
      in normotensive subjects possibly due to above mentioned anti-vasoconstrictor
      effects of insulin. In contrast, insulin-induced anti-vasoconstrictor mechanisms
      may be lost in hypertensive subjects, which may result in hypertension.

PMID- 9240765
TI  - Obesity and the insulin resistance syndrome.
AB  - Obesity is one component of a risk factor constellation that consists of insulin
      resistance (and/or hyperinsulinemia), hypertension, and a dyslipidemia
      characterized by a low HDL cholesterol level and high triglyceride levels. This
      risk factor constellation, which conveys enhanced risk for cardiovascular
      disease, is sometimes referred to as the "insulin resistance syndrome", "syndrome
      x", or the "metabolic" syndrome. Although the hyperinsulinemia and insulin
      resistance associated with the syndrome appear to play a central role, the
      relationship between insulin and the other manifestations of the syndrome have
      remained obscure.

PMID- 9240766
TI  - Relationships between reduction in body weight and reduction in blood pressure
      and improvement of glucose and lipid metabolism induced by short-term calorie
      restriction in overweight hypertensive women.
AB  - We investigated the correlations between the reduction in body weight (BW)
      induced by calorie restriction and reductions in blood pressure (BP) and
      improvement in metabolic disorders in overweight women with essential
      hypertension. After eating a standard diet (diet-I) for 2 weeks, women in the
      calorie-restricted group (n = 25) received a low calorie diet for 2 weeks, and
      then standard diet-II for 1 week. Women in the calorie-nonrestricted group (n =
      13) ate standard diet-I for 5 weeks. The calorie-restricted group exhibited a
      significant reduction in BP in association with loss of BW; their levels of low
      density lipoprotein cholesterol, and triglycerides levels, and their fasting
      levels of glucose and insulin were also reduced compared with the calorie
      nonrestricted group. However, there were no significant differences in the level
      of high-density lipoprotein cholesterol, the areas under the 2-h glucose and
      insulin curves (AUC(glu) and AUC(ins)), or the ratio of AUC(glu) to AUC(ins)
      between groups. The change in BW was significantly correlated with a reduction in
      BP (r= 0.62, p < 0.01), but not with an improvement in metabolic disorders.
      Findings suggest that the degree of BW loss, induced by short-term, severe
      calorie restriction is associated with BP reduction, but not with improvements in
      glucose and lipid metabolism in overweight hypertensive women.

PMID- 9240767
TI  - Insulin resistance seen in non-insulin dependent diabetes mellitus and
      hypertension.
AB  - The characteristics of NIDDM seen in Japanese is coexistence of diminished
      insulin secretion and the impaired sensitivity to insulin in the target tissues.
      Thus, insulin resistance does not mean hyperinsulinemia. To investigate the organ
      specific insulin action on glucose homeostasis, we developed an innovative non
      invasive method, using an euglycemic hyperinsulinemic clamp combined with oral
      glucose load. With this procedure, we could reveal muscle glucose uptake and
      hepatic glucose uptake following oral glucose load, quantitatively, separately
      and simultaneously. The effect of strict glycemic control in non-obese NIDDM who
      were secondary failure to sulfonylurea with 3 times prandial regular insulin
      injections, on glucose disposals are investigated. Glucose disposal by peripheral
      tissues was not altered (clamped blood glucose and insulin concentration are, 90
      mg/dl and 200 microU/ml, respectively). The ratio of splanchnic glucose disposal
      to the amount of ingested glucose, on the other hand, significantly increased to
      33.1% from 14.5%. Therefore, short-term strict glycemic control appears to
      improve glucose handling by splanchnic tissues without affecting insulin
      sensitivity of peripheral tissues in NIDDM. This method would be feasible to
      investigate whether insulin resistance seen in hypertensive patients, is located
      only in peripheral tissues or is also in the liver. To find patients with
      asymptomatic atherosclerosis, we routinely apply a noninvasive maneuver using
      high resolution B-mode imaging of the carotid artery, to determine
      atherosclerosis quantitatively. Impaired glucose tolerance (IGT) male subjects
      showed significantly greater thickness of the intimal plus medial complex (IMT)
      than age-matched healthy males and showed no significant differences compared to
      age-matched NIDDM patients. Among IGT, those with exaggerated insulin secretion
      (average serum insulin concentration was 100 microU/ml at 1 and 2 h after), in
      other words, insulin resistant, showed thicker IMT. The characteristics of IGT
      groups with high insulin level were, BMI more than 25, diastolic blood pressure
      more than 83 mmHg, serum triglyceride more than 215 mg/dl. Thus, among mildly
      obese, mild hypertensive, mild glucose intolerant, slightly hypertriglyceridemic
      Japanese male subjects, there exist advanced atherosclerotic subjects.

PMID- 9240768
TI  - Hypertension and serum Mg in the patients with diabetes and coronary heart
      disease.
AB  - Interrelations between hypertension (HT), ischemic heart disease (IHD) and
      diabetes mellitus (DM) were investigated in the diabetic subjects without IHD (DM
      group) or with IHD (DM + IHD group) and subjects with IHD (IHD group) which were
      not complicated with DM. 1. The incidence of hypertension of DM group, DM+IHD
      group and IHD group is 40, 54, 38% respectively. 2. The incidence of
      hyperlipidemia of DM group, DM + IHD group and IHD group is 55, 71, 56%
      respectively. 3. Serum Mg levels of DM (1.9 +/- 0.37 mg/dl), DM + IHD (1.8 +/-
      0.23) and IHD (1.9 +/- 0.33) were significantly lower than that of normal control
      (2.3 +/- 0.32). 4. Serum Mg level of poorly controlled diabetic patients is lower
      than that of well controlled diabetic patients. These results suggested that
      Magnesium deficient state is one of the cause of insulin resistancy.

PMID- 9240769
TI  - Intra-abdominal fat, lipid metabolism and insulin resistance in coronary artery
      disease.
AB  - To investigate the metabolic and atherogenic effect of intra-abdominal fat
      accumulation, we examined correlation between variables of lipid and glucose and
      the fat distribution of abdominen by using computed tomography. Subjects were 292
      of male and 161 of female who underwent coronary angiography. Intra-abdominal fat
      area was correlated with insulin concentration at 120 min in oral glucose
      tolerance tests and triglyceride level in male, on the other hand, in female were
      HDL-cholesterol level, apolipoprotein B, glucose area under curve and insulin
      concentration at 60 and 120 min. In an aspect of atherogenic effect of intra
      abdominal fat, it was not atherogenic in isolated state in male, but atherogenic
      in diabetic female. Intra-abdominal fat was accompanied with hypertension and mid
      band, which appeared between alpha and beta band in polyacrylamide diskgel
      electrophoresis. Cluster of intra-abdominal fat accumulation, hypertension and
      mid-band was atherogenic in male, in which insulin resistance play an important
      role in the coronary artery disease. On the contrary, intra-abdominal fat
      accumulation accompanied with exacerbation of glucose tolerance, hypertensive and
      high level of apolipoprotein B in female. We concluded that visceral fat
      accumulation was a generator of metabolic syndrome X in male and was a
      progression factor for diabetes, hypertensive and high apolipoprotein B level in
      female.

PMID- 9240770
TI  - Antihypertensive treatment in insulin resistant patients.
AB  - Epidemiological evidence suggests that treatment with beta-blockers and diuretics
      increase the risk to develop diabetes. Prospective, randomized studies of
      antihypertensive drugs have demonstrated differences between different classes of
      drugs regarding effects on insulin sensitivity. Thus treatment with beta-blockers
      or diuretics is associated with impairment in insulin sensitivity, whereas most
      modern calcium-channel blockers and angiotensin converting enzyme inhibitors are
      neutral. However, captopril treatment seems to be different and result in
      improvement of insulin sensitivity. The most pronounced improvements have been
      obtained with alpha1-blockers. In populations at high risk for diabetes, it may
      be justified to select drugs that improve insulin sensitivity when treating
      hypertension in insulin resistant individuals.

PMID- 9240771
TI  - Clinical impact of insulin resistance syndrome in cardiovascular diseases and its
      therapeutic approach.
AB  - In subjects with coronary artery diseases (obstructive and vasospastic angina
      pectoris (AP)) who have no diabetes, hypertension, obesity and physical
      inactivity, insulin sensitivity was significantly reduced with compensated
      hyperinsulinemia on OGTT. Insulin resistance significantly correlated with
      coronary atherosclerosis score. In vasospastic AP (VAP), those who fulfilled more
      than 3 risk factors out of 5 (hyperinsulinemia, obesity, glucose intolerance,
      hypertension, dyslipidemia) consist of 70 and 40% for smokers and nonsmokers
      respectively. Insulin resistance syndrome who fulfilled all the criteria was 9
      10% for VAP. In atherothrombotic brain infarction (ATTI) with the same exclusion
      criteria, the similar insulin resistance and hyperinsulinemia have been observed,
      but not in embolic (cardiac origin) or lacunar infarction. In ATTI, high TG and
      apo B with low HDL-chol were noted in blood. In essential hypertension without
      diabetes and obesity, hyperinsulinemia was noted in 25-35% and insulin resistance
      in 56-88%. Reduction of blood pressure with alpha blocker (bunazosin), ACE
      inhibitor (cilazapril), long-acting Ca++ blocker (amlodipine) significantly
      improved lowered insulin sensitivity. Insulin resistance rather than
      hyperinsulinemia is more closely associated with blood pressure. Cardiovascular
      diseases (vasospastic and obstructive AP, brain cortical artery diseases) are
      prone to develop diabetes because of insulin resistance and also promote the
      generation of cumulative risk factors resulting in a vicious cycle. Efforts to
      alleviate insulin resistance is crucial for the primary and secondary prevention
      of cardiovascular diseases.

PMID- 9240772
TI  - Effect of exercise on hypertension and associated complications.
AB  - Both cross-sectional and longitudinal epidemiological studies have shown that
      sedentary life style elevates blood pressure. Antihypertensive effectiveness of
      physical exercise has been also proven for the past ten years. We have carried
      out nine, (mostly controlled comparative) studies in the past over ten years. The
      mean changes of blood pressure by mild (approximately 50% maximum oxygen uptake)
      intensity cycle ergometer (60 min X 3 times a week X 10 week) in the controlled
      studies was -11/-6 mmHg. We found two mechanisms involved, a) sympathicolytic
      action and b) plasma depletion. Exercise not only lower blood pressure, but it is
      also known to improve lipid and glucose metabolism, and hence insulin sensitivity
      as has been applied for the therapy of diabetes mellitus. Exercise, therefore,
      should theoretically prevent cardiovascular diseases, and in fact, a prospective
      large scale epidemiological study has suggested that exercise will prevent
      cardiovascular death.

PMID- 9240773
TI  - The use and costs of physician services for ophthalmic surgical procedures in
      1988 and 1991.
AB  - BACKGROUND AND OBJECTIVE: To examine the change in volume and costs of physician
      services for ophthalmic surgical procedures associated with physician fee cuts.
      MATERIALS AND METHODS: The authors analyzed the physician claims (Part B) data
      for a 5% random sample of the Medicare population. Number, rate, average allowed
      charge, and total cost of physician services for ophthalmic surgical procedures
      were compared for 1988 and 1991. RESULTS: An estimated 3.1 million (98 per 1000)
      ophthalmic surgical procedures were performed on Medicare beneficiaries in 1991,
      compared with 2.3 million (76 per 1000) in 1988. There was a 35% increase in
      number and a 28% increase in rate. The average allowed charge for these services
      decreased by 26% ($1155 vs $852 per procedure), with an overall cost of $2.6
      billion in both years. CONCLUSION: A reduction in fee for physician services for
      ophthalmic surgical procedures from 1988 to 1991 was associated with an increase
      in the volume of the services. The overall costs of physician services for
      ophthalmic surgical procedures remained consistent between the two years.

PMID- 9240774
TI  - The results of ab interno laser thermal sclerostomy combined with cataract
      surgery versus trabeculectomy combined with cataract surgery 6 to 12 months
      postoperatively.
AB  - BACKGROUND AND OBJECTIVE: When cataract surgery and glaucoma surgery are
      combined, the theoretical advantages of pressure control, removal of the visual
      impairment, and protection against an increase in intraocular pressure (IOP) in
      the immediate postoperative period are gained. The authors' objective was to
      determine whether ab interno laser thermal sclerostomy (LTS) combined with
      cataract surgery would be as effective as trabeculectomy combined with cataract
      surgery. PATIENTS AND METHODS: Ab interno LTS was compared with trabeculectomy,
      retrospectively, for patients who had undergone combined cataract and glaucoma
      surgery. RESULTS: There was no significant difference in the numbers of patients
      using no medications or fewer medications at 6 and 12 months. There was a greater
      reduction in IOP in the LTS group. CONCLUSIONS: LTS may be better than
      trabeculectomy in combined cataract and glaucoma surgery because it reduces the
      IOP more. Compared with trabeculectomy, LTS is simpler to perform and adds less
      operating time to cataract surgery. Continued follow-up is recommended.

PMID- 9240775
TI  - Cataract surgery after trabeculectomy.
AB  - BACKGROUND AND OBJECTIVE: To determine the effect of cataract surgery on
      glaucomatous eyes with good intraocular pressure (IOP) control after
      trabeculectomy. PATIENTS AND METHODS: Twenty-two eyes with functional blebs that
      underwent cataract extraction were retrospectively analyzed. RESULTS: The mean
      (+/- SD) preoperative IOP was 11.0 +/- 4.3 mm Hg. The mean (+/- SD) postoperative
      IOPs at 1, 2, 6, and 9 months were 15.5 +/- 4.9, 12.6 +/- 4.7, 14.6 +/- 5.6, and
      19.0 +/- 7.9 mm Hg, respectively. At each interval except for the second month,
      the mean IOP was statistically significantly higher than the preoperative value
      (P = .0003, .24, .02, and .0009, respectively). The total number of medications
      was also higher (3 preoperatively versus 27 postoperatively). The interval
      between the two surgeries had no influence on IOP control. Intraoperative
      complications during cataract surgery, particularly vitreous loss, were
      associated with poor IOP control. Phacoemulsification had less of an effect on
      the postoperative IOP control than did extracapsular cataract extraction.
      CONCLUSIONS: Eyes with previous successful trabeculectomies had higher IOPs and
      required more medications after subsequent cataract surgeries.

PMID- 9240776
TI  - The course after cataract extraction, intraocular lens implantation, and
      trabeculectomy for patients with diabetes.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the postoperative recovery of the anterior
      segment and the course of diabetic retinopathy following a combined procedure of
      an extracapsular cataract extraction with posterior chamber intraocular lens
      implantation and trabeculectomy in diabetic patients with glaucoma. PATIENTS AND
      METHODS: The records of diabetic patients with uncontrolled glaucoma and
      cataract, who underwent a combined procedure in one eye, were retrospectively
      reviewed. RESULTS: Eleven patients were included. The mean intraocular pressure
      and the amount of antiglaucomatous medications required to control it were both
      reduced postoperatively. Anterior segment complications included hyphema in 4
      eyes (37%), fibrin formation in 4 eyes (37%), and posterior synechia in 3 eyes
      (27%). The hyphema resolved spontaneously and the fibrin disappeared following
      increased administration of steroids. Development of diabetic retinopathy
      occurred in 1 eye (9%). Cystoid macular edema without other evidence of diabetic
      retinopathy was observed in 1 eye (9%). CONCLUSION: The control of intraocular
      pressure is improved in diabetic patients who have undergone this combined
      procedure. The postoperative course in these diabetic patients is similar to that
      previously described in the general population.

PMID- 9240777
TI  - Intraoperative and postoperative use of mitomycin-C in the treatment of primary
      pterygium.
AB  - BACKGROUND AND OBJECTIVE: The effectiveness of 0.04% mitomycin-C, either
      postoperatively for 2 weeks or intraoperatively as a single dose, as an adjunct
      in the surgical treatment of primary pterygium was evaluated. PATIENTS AND
      METHODS: Mitomycin-C was used in addition to the bare sclera technique in 43 eyes
      with pterygia. The mean follow-up time was 18.5 months for the 24 eyes in the
      postoperative mitomycin-C group, 10.3 months for the 19 eyes in the
      intraoperative mitomycin-C group, and 17.3 months for the 17 eyes in the control
      group (eyes that had undergone surgical excision only). RESULTS: The recurrence
      rate was 4.2% with postoperative administration, 5.3% with intraoperative
      application, and 41.2% in the control group. There was a significant reduction in
      recurrence rates for both the postoperative and the intraoperative mitomycin-C
      groups compared with the control group (P = .005 and P = .01, respectively).
      However, recurrence rates were not statistically different according to the type
      of application. No serious side effect occurred during the follow-up period.
      CONCLUSION: Topical mitomycin-C, either intraoperatively or postoperatively, as
      an adjunct decreases the recurrence rate of primary pterygium. Intraoperative
      application seems advantageous because it decreases the symptomatic side effects
      and restricts the inappropriate use by the patient.

PMID- 9240778
TI  - External dacryocystorhinostomy without mucosal flaps: comparison of petroleum
      jelly gauze nasal packing with gelatin sponge nasal packing.
AB  - BACKGROUND AND OBJECTIVE: This study was designed (1) to determine the overall
      success of patients who underwent external dacryocystorhinostomy (DCR) using a
      modified Kasper technique without lacrimal sac and nasal mucosal sutured flaps,
      and (2) to investigate the possible impact of intraoperative petroleum jelly
      gauze nasal packing as compared with gelatin sponge nasal packing on the surgical
      results. PATIENTS AND METHODS: A retrospective review of 122 consecutive patients
      who underwent external DCR using a modified Kasper technique was performed.
      Patients were divided into two groups based on use of petroleum jelly gauze
      packing or gelatin sponge packing. Criteria for successful surgery included
      resolution of the main symptom(s) of tearing, chronic mucous discharge (chronic
      dacryocystitis), and/or recurrent acute dacryocystitis; and patency of the
      reconstructed lacrimal system. RESULTS: Ninety-four of 96 patients who had
      petroleum jelly gauze packing had successful DCRs, whereas only 21 of 26 patients
      who had gelatin sponge packing had successful DCRs (P < .005). Soft tissue rather
      than bony obstruction of the rhinostomy was the most common cause of DCR failure,
      as confirmed by office probing, endoscopy, and computed tomography. Three
      patients in the gelatin sponge packing group who experienced failure subsequently
      had bacterial sinusitis. CONCLUSION: This study strongly suggests that gelatin
      sponge nasal packing, at least when used for patients who undergo DCR without
      sutured mucosal flaps, may be associated with an increased number of failures as
      a result of scar tissue formation at the rhinostomy site, as compared with
      petroleum jelly packing. Petroleum jelly gauze nasal packing may enhance surgical
      results by reducing scarring between the lacrimal sac fistula and the nasal
      structures.

PMID- 9240780
TI  - Management of idiopathic macular holes.

PMID- 9240779
TI  - Progressive increase in the quantity of deviation in congenital esotropia.
AB  - BACKGROUND AND OBJECTIVE: It was the author's clinical impression that many
      individuals with congenital esotropia demonstrated an increase in the quantity of
      deviation measured over time. The present study statistically examines the
      prevalence and quantity of increase in the amount of deviation measured for a
      consecutive series of patients with congenital esotropia prior to surgical
      alignment. PATIENTS AND METHODS: A retrospective chart review was conducted for
      patients treated during a 5-year period. Data were recorded for the initial and
      final measurements of the strabismus and the initial and final surgical plans
      prior to surgery. Also recorded were the age at surgery, length of observation
      before surgery, refraction, use of patching, and initial motor alignment outcome.
      RESULTS: Approximately 50% of 41 patients showed an average increase of 20 prism
      diopters (PD) in the quantity of the deviation when they were observed for an
      average of 3 months. The age at initial measurement, age at surgery, length of
      observation prior to surgery, refraction, or use of patching could not be used to
      identify patients with the increase in the amount of strabismus. However, in
      cases where the final surgical plan was based on the measurements made the day
      before surgery, 90% of the patients showed an initial surgical alignment to
      within 10 PD or orthotropia by 6 weeks postoperatively. CONCLUSIONS: These data
      indicate that a significant increase in the amount of preoperative deviation is
      very prevalent in patients being observed for congenital esotropia. This finding
      suggests that the timing of preoperative measurements is very important, and that
      the data collected close to the date of surgery are the most important with which
      to plan surgery.

PMID- 9240781
TI  - Treatment of presumed fungal endophthalmitis with oral fluconazole.
AB  - Amphotericin B is the usual treatment for fungal endophthalmitis, but its
      toxicity and lack of oral bioavailability may limit its use in some patients. The
      authors report the successful management of two cases of presumed metastatic
      fungal endophthalmitis with oral fluconazole, a bis-triazole compound with a
      broad antifungal spectrum.

PMID- 9240782
TI  - Enlarged extraocular muscles from metastatic signet ring carcinoma.
AB  - Enlarged extraocular muscles usually occur from inflammatory conditions, but in
      rare instances metastatic tumors that invade the muscles will require a biopsy
      and specific treatment. The authors report what they believe to be the third case
      of metastases to the extraocular muscles from signet ring cell adenocarcinoma of
      an unknown primary site.

PMID- 9240783
TI  - Retinal irradiation from an operating microscope during vitrectomy: observation
      by endoscopy.
AB  - Phototoxic retinopathy due to light from the operating microscope has been
      reported during cataract surgery, as well as during vitreous surgery. A neutral
      density filter for the coaxial light or coverage of the cornea with various
      materials has been advocated to prevent retinal complications. However, it is
      difficult to actually monitor the fundus during surgery with usual methods. The
      author used an endoscope to demonstrate how intensively the light from the
      operating microscope is focused on the retinal surface during vitreous surgery.

PMID- 9240784
TI  - Orbitotomy facilitated by a mechanical retraction system.
AB  - A series of arms and retractors that attach to the operating table to aid the
      surgeon during orbitotomy and dacryocystorhinostomy is described. This enables
      the surgeon to consistently retract and expose orbital structures without
      assistance.

PMID- 9240786
TI  - The bully pulpit.

PMID- 9240785
TI  - Visual acuity immediately following phacoemulsification with subconjunctival
      anesthesia.
AB  - The authors attempted to discover the quality of vision experienced immediately
      after cataract surgery by those patients receiving subconjunctival anesthesia and
      no postoperative patching. Eighty-five consecutive patients who underwent
      phacoemulsification were studied. Anesthesia was topical tetracaine followed by a
      subconjunctival injection of a lidocaine-bupivicaine hydrochloride-hyaluronidase
      mixture. Visual acuities were measured within a half hour after surgery and at 1
      day postoperatively. Immediate postoperative visual acuities ranged from 20/25 to
      20/200. Visual acuities were 20/40 or better in 14 patients (16.4%), 20/50 to
      20/60 in 22 patients (23.5%), and 20/70 to 20/200 in 49 patients (60.1%). The
      early postoperative visual acuity measurements vary widely. There was a marked
      improvement at 1 day after surgery, with acuities becoming more aligned with
      expected outcomes.

PMID- 9240787
TI  - Disorders of the distal radioulnar joint.
AB  - Disorders of the distal radioulnar joint can be classified into functional
      abnormalities based on instability, incongruity of the joint surface, impaction,
      and isolated triangular fibrocartilage complex tears. Knowledge of the type of
      lesion aids in selecting the treatment option best suited to correcting each
      problem. This review begins by summarizing the anatomy of the distal radioulnar
      joint. It then examines the various clinical problems that may arise in this
      complicated anatomic area and outlines the different surgical and nonsurgical
      options available to treat these disorders. The most important aspect in
      treatment of disorders of the distal radioulnar joint is early recognition,
      followed by prompt appropriate surgical or nonsurgical management.

PMID- 9240789
TI  - Sliding osteotomy of the greater trochanter.
AB  - Trochanteric osteotomy is commonly used to facilitate surgical exposure in
      difficult cases of total hip arthroplasty or acetabular fracture fixation. In
      this paper, we report our experiences using the sliding trochanteric osteotomy
      performed in 3 patients for acetabular fracture fixation and in 2 patients with
      total hip arthroplasty. Using the sliding trochanteric osteotomy technique
      facilitates improved exposure, reduction, and internal fixation of acetabular
      fractures, especially those involving the dome and the posterior wall. Sliding
      osteotomy of the trochanter also permits trochanteric advancement when the
      abductors are weak or the prosthesis is unstable during total hip arthroplasty.
      No significant complications occurred from this technique, and the postoperative
      clinical course was satisfactory in all patients.

PMID- 9240788
TI  - Counterparalysis for treatment of paralytic scoliosis with botulinum toxin type
      A.
AB  - In this study, botulinum toxin was used to treat paralytic scoliosis. Twelve
      children with paralytic scoliosis and severe, complicating additional diseases
      required surgical delay. Although this use of botulinum toxin is experimental,
      alternative treatments posed greater risks. An institutional review board
      protocol for nonestablished dosage and indication for treatment was initiated to
      monitor safety and effect. Treatment was intended to supplement, not replace,
      other desirable treatment modalities. The effect was to be measured by the return
      of efficacy of conservative treatment in halting curve progression. Short-term
      results show that none of the children had worsened scoliosis; all had some
      reduction in curve measurement (up to >50 degrees).

PMID- 9240790
TI  - Multifocal heterotopic ossification in a patient with sickle cell disease: a case
      report.
AB  - A patient had a sickle cell crisis and developed heterotopic ossification of
      multiple joints. Many disease entities have been associated with heterotopic
      ossification; however, heterotopic ossification has rarely, if ever, been
      associated with sickle cell disease. Only 10% of patients with heterotopic
      ossification develop ankylosis of their joints. This patient developed ankylosis
      of several joints. Surgical excision of the periarticular heterotopic
      ossification allowed full passive motion of the involved joints. After extensive
      rehabilitation, the patient could perform all activities of daily living and
      ambulate comfortably without devices.

PMID- 9240791
TI  - Dysplasia epiphysealis hemimelica in an elderly patient.
AB  - We report a case of dysplasia epiphysealis hemimelica in an 87-year-old woman,
      the oldest patient, to our knowledge, who has presented with symptoms from this
      disease. Whereas the classic presentation is marked by painless swelling and/or
      deformity, our patient was found to be diffusely tender without effusion or gross
      deformity. Plain radiographs showed severe degenerative changes in her right knee
      with loss of joint space and osteophyte formation, along with an intra-articular
      osteochondroma. The intra-articular osteochondroma was removed, and an
      arthroplasty was performed without complication and with full relief of symptoms.

PMID- 9240792
TI  - Incarcerated subhallucal sesamoid of the great toe: irreducible dislocation of
      the interphalangeal joint of the great toe by an accessory sesamoid bone.
AB  - A case of irreducible dislocation of the interphalangeal joint of the great toe
      caused by interposition of the subhallucal sesamoid bone is described. The
      pitfalls of diagnosis and treatment of this uncommon dislocation are described,
      together with a historical review of the literature.

PMID- 9240793
TI  - Draping of the pelvis and proximal femur: an improved method for applying self
      adherent plastic drapes.
AB  - It can be difficult to isolate the operative field from the perineum when draping
      for procedures involving the pelvis or proximal femur. A draping technique using
      two self-adherent plastic sheets is described; it reliably creates a watertight
      seal around the perineum yet allows substantial movement of the leg during the
      procedure.

PMID- 9240795
TI  - Geographic distribution of pediatricians in the United States: an analysis of the
      fifty states and Washington, DC.
AB  - OBJECTIVES: To determine current geographic distribution of pediatricians in the
      United States, to assess the changes in the geographic distribution of
      pediatricians between 1982 and 1992, and to identify factors associated with the
      distribution of pediatricians among the 50 states. METHODS: A data set was
      constructed using several published data sources including the American Medical
      Association Physician Masterfile as the principal source for physician
      information. The pediatrician-to-child population ratio (PCPR, the number of
      pediatricians per 100 000 people under 18 years of age) was calculated to compare
      the distribution of pediatricians among states and the distributional changes
      between 1982 and 1992. Lorenz curves and Gini indices were used to describe
      distributions and to compare distributions across time periods. Linear regression
      analysis was performed to assess the relationship between PCPR (dependent
      variable) with 9 predictor variables. RESULTS: Between 1982 and 1992, there was a
      5.4% increase in the United States (US) child population and a 46.1% increase in
      the number of pediatricians in patient care. During that time period, the PCPR
      increased by 38.6% from 35.1 per 100 000 to 48.6 per 100 000. There was a more
      than 4-fold difference in the PCPRs of the highest state (Maryland, 84.3) and the
      lowest state (Idaho, 18.5) in 1992. The PCPR increased in all 50 states, but
      varied from a 4.1% increase in Wyoming to a 63.4% increase in Massachusetts. The
      Lorenz curve showed that pediatricians were less evenly distributed than all
      physicians, but more evenly distributed than pediatric cardiologists. Between
      1982 to 1992 the Gini index decreased 9.8% for all physicians and 10.2% for
      pediatric cardiologists, but only 1. 9% for pediatricians. Since a decrease in
      the Gini index signifies better overall distribution, these changes are
      relatively modest for pediatricians as a whole, especially when compared to other
      physicians. Regression analysis showed that a higher PCPR was associated with a
      greater number of residency positions per 100 000 children and with the per
      capita income of the state (R = .93). CONCLUSIONS: The distribution of
      pediatricians does not parallel the distribution of the child population in the
      US, nor has this distribution changed substantially in spite of a 38.6% increase
      in the PCPR. Pediatricians tend to concentrate in states with high per capita
      income and in states with a larger number of residency training positions. The
      failure of market forces to improve the geographic distribution may require
      manpower policy changes designed to improve distribution in underrepresented
      states. The uncertain impact of market changes due to increased use of managed
      care could affect distributional requirements of pediatricians in the future.

PMID- 9240794
TI  - Why would you remove half a brain? The outcome of 58 children after
      hemispherectomy-the Johns Hopkins experience: 1968 to 1996.
AB  - PURPOSE: To report the outcomes of the 58 hemispherectomies performed at Johns
      Hopkins between 1968 and January 1996. METHODS: Charts were reviewed of the 58
      hemispherectomies performed at Johns Hopkins Medical Institutions by the
      Pediatric Epilepsy Group during the years 1968 to 1996. Twenty-seven operations
      were done for Rasmussen's syndrome, 24 operations for cortical
      dysplasias/hemimegalencephalies, and 7 for Sturge-Weber syndrome or other
      congenital vascular problems. Seizure control alone did not seem to adequately
      describe the outcomes of the procedure. Therefore, a score was constructed that
      included seizure frequency, motor disability, and intellectual handicap. This
      burden of illness score better described the child's handicap before and after
      surgery. RESULTS: Perioperative death occurred in 4 out of 58 children. Of the 54
      surviving children, 54% (29/54) are seizure-free, 24% (13/54) have
      nonhandicapping seizures, and 23% (12/54) have residual seizures that interfere
      to some extent with function. Reduction in seizures was related to the etiology
      of the unilateral epilepsy. Eighty-nine percent of children with Rasmussen's, 67%
      of those with dysplasias, and 67% of the vascular group are seizure-free, or have
      occasional, nonhandicapping seizures. All operations were considered by the
      parents and the physicians to have been successful in decreasing the burden of
      illness. In 44 the procedure was very successful, in 7 it was moderately
      successful, and in 3 it was minimally successful. Success was related to the
      etiology, and early surgery was preferable. CONCLUSION: Hemispherectomy can be a
      valuable procedure for relieving the burden of seizures, the burden of
      medication, and the general dysfunction in children with severe or progressive
      unilateral cortical disease. Early hemispherectomy, although increasing the
      hemiparesis in children with Rasmussen's syndrome, relieves the burden of
      constant seizures and allows the child to return to a more normal life. In
      children with dysplasias, early surgery can allow the resumption of more normal
      development.

PMID- 9240796
TI  - Associated malformations in infants with cleft lip and palate: a prospective,
      population-based study.
AB  - OBJECTIVE: Infants with cleft lip and palate may often have other associated
      congenital defects although the reported incidence and the types of associated
      malformations vary between different studies. The purpose of this investigation
      was to assess the prevalence of associated malformations in a geographically
      defined population. METHODS: The prevalence of associated malformations in
      infants with clefts were collected prospectively between 1975 to 1992 on all
      infants born in greater Stockholm, Sweden. The patient records were also compared
      with data from the National Malformation Registry and other hospital records if
      any. RESULTS: Of the 616 cleft infants (367 boys, 249 girls) born during this
      period, 21% had associated malformations that either required follow-up or
      treatment. Associated malformations were more frequent in infants who had both
      cleft lip and palate (28%) than in infants with isolated cleft palate (22%) or
      infants with isolated cleft lip (8%). Malformations of the upper or lower limbs
      or the vertebral column were the most common other anomalies and accounted for
      33% of all associated defects. Twenty-four percent of associated malformations
      were in the cardiovascular system and congenital heart disease was the most
      common isolated associated malformation. Fifteen percent of all associated
      malformations were multiple and they were frequently associated with mental
      retardation or chromosomal anomalies. Twenty-two percent of infants with
      associated malformations were born preterm, compared with an expected 5%
      incidence of preterm delivery in Sweden. CONCLUSION: A more extensive cleft seems
      to be associated with a higher risk for associated malformations. Although many
      associated congenital defects can be detected at a physical examination, the high
      prevalence of congenital heart disease (16 times that of general population) may
      justify a routine echocardiographic screening.

PMID- 9240797
TI  - The Red Alert Program for life-threatening asthma.
AB  - OBJECTIVE: To design a program to prevent death in children with life-threatening
      asthma. METHODS: Using published guidelines to identify patients with life
      threatening asthma, we developed a comprehensive medical network involving
      emergency medical services, school workers, extended family members, local
      physicians, emergency rooms, and a referral center. The network was designed to
      provide early, aggressive medical attention and rapid access to care for patients
      enrolled in the program. RESULTS: In 8 years of operation, 75 patients have been
      enrolled. There have been 270 hospitalizations, with life-threatening asthma
      occurring in 25 admissions in 15 patients. Three patients have died; of these,
      two did not use the services provided by the program. CONCLUSIONS: The Red Alert
      Program has been successful in assuring more aggressive and timely intervention
      for asthma attacks and seems to have prevented deaths. Patients and their
      families express a high degree of satisfaction with the services. The Red Alert
      Program may serve as a model for other programs for children with life
      threatening asthma.

PMID- 9240798
TI  - A program to immunize hospitalized preschool-aged children: evaluation and
      impact.
AB  - OBJECTIVE: The Standards for Pediatric Immunization Practices suggest that
      hospitalization be viewed as an opportunity to vaccinate children. The purpose of
      the present study is 1) to determine the immunization status of an urban
      population of hospitalized preschool-aged children, 2) to study the impact of an
      immunization program designed to vaccinate hospitalized 0 to 2-year-old children
      who are underimmunized at admission, and 3) to make immunization a routine part
      of care for the hospitalized child. METHODS: Prospective evaluation of the
      immunization status of hospitalized 0 to 2-year-old residents of Philadelphia
      admitted to an urban children's hospital was performed. With verification of the
      child's immunization record through the primary care provider (PCP), needed
      immunizations were given and records were forwarded to notify the PCP.
      Educational information was provided to families and health care providers. MAIN
      OUTCOME MEASURE: The percentage of children fully immunized on admission compared
      with the percentage at the time of discharge. Results. Two thousand three hundred
      twenty-nine children from 0 to 2 years of age were hospitalized during the 22
      month study period. Immunization records were verified in 86% (2006), requiring
      an average of 1.5 phone calls to the PCP. The mean patient age was 10 months.
      Average hospital length of stay was 4 days. On admission, 49% (980) of the 2006
      study patients were fully immunized. The remaining 51% (1026) were eligible for
      vaccination. Immunizations were delayed greater than or equal to 2 months in 18%
      (355) of the children. Neither type of health care insurance nor site of primary
      care affected the immunization status of those evaluated at the time of
      admission. Sixty-six percent (N = 674) of eligible patients received at least one
      vaccination before hospital discharge. Medical contraindications accounted for
      only 4% of the reasons eligible patients were not immunized. Of the 2006 children
      evaluated, the percentage of those fully vaccinated for age increased
      significantly from 44% on admission to 70% on discharge. CONCLUSION: As a result
      of this program, there was a significant improvement in vaccination percentage at
      the time of hospital discharge in this group of urban preschool-aged children.
      The development of an immunization program to vaccinate hospitalized preschool
      children is an opportunity to immunize in the urban setting where there is a high
      prevalence of underimmunization. In addition, it provides an opening for
      educational programs for families, nurses, and housestaff and linkage to the
      community PCPs.

PMID- 9240799
TI  - Expenditures for care of children with chronic illnesses enrolled in the
      Washington State Medicaid program, fiscal year 1993.
AB  - OBJECTIVE: We calculated expenditures for children with one of eight selected
      chronic health conditions who were enrolled in the Washington State Medicaid
      program and compared them with payments for all Medicaid-enrolled children. We
      examined variation in mean, median, and total expenditures and identified
      expenditure sources. METHODS: This study analyzed Medicaid claims data for 310
      977 children aged 0 to 18 who were enrolled at any time in fiscal year 1993.
      Tracer conditions were used to examine expenditure variation within and between
      diagnostic groupings. A total of 18 233 children (5.9%) had at least one of the
      conditions. Expenditures were calculated based on payments made by the Medicaid
      program. RESULTS: Children with one of the eight selected conditions incurred
      mean expenditures of $3800, compared with $955 for all Medicaid-enrolled
      children. Mean payments associated with the selected conditions ranged from 2.5
      times to 20 times more than payments to all children. Approximately 10% of
      children accounted for approximately 70% of the payments in general and in each
      diagnostic grouping. Variation in mean, median, and total expenditures was
      extensive among the conditions. For most conditions, inpatient stays accounted
      for the greatest proportion of expenditures; for some conditions, durable
      equipment, home nursing, and medication-related services accounted for
      substantial proportions of total expenditures. CONCLUSIONS: Medical care for
      children with selected chronic health conditions is 2.5 to 20 times more
      expensive than children in general, depending on the condition. A relatively few
      children account for the majority of expenditures. Extensive variation in mean,
      median, and total expenditures suggests that different conditions will need to be
      kept distinct for purposes of establishing payment rates. Children with certain
      conditions are vulnerable to restrictions in specific services, depending on what
      restrictions are imposed by a financing program. Further analyses are needed to
      identify risk-adjustment strategies to support delivery of high-quality services
      to this population of children as they migrate into managed-care environments.

PMID- 9240800
TI  - End-of-life care in cystic fibrosis.
AB  - OBJECTIVE: End-of-life clinical care in cystic fibrosis (CF) differs
      substantially from terminal care in childhood cancer. To examine this difference,
      we reviewed the medical care of a cohort of CF patients treated at Children's
      Hospital, Boston, to document the use of preventive, therapeutic, and palliative
      care in the month preceding death. PATIENTS: We reviewed the medical records of
      44 patients older than 5 years who died of CF-related respiratory failure for the
      years 1984 to 1993. RESULTS: Thirty-eight patients (86%) received opiates for the
      treatment of severe dyspnea and pain; the duration of opiate use varied from less
      than 1 hour to greater than 1 month. The dose of opiates varied from less than 5
      mg per hour to greater than 30 mg per hour. Thirty-three patients (75%) continued
      to receive intravenous antibiotics in the last 12 hours of life; 32 (72%)
      continued to receive preventive or therapeutic oral medications in the last 12
      hours of life. All patients were designated as do not resuscitate at the time of
      death; 43 of the patients died in the hospital with 1 patient dying at home under
      hospice care. CONCLUSIONS: The model of comfort care developed in childhood
      cancer does not adequately describe the combination of preventive, therapeutic,
      and palliative care given at the end of life for CF at our institution. The
      majority of CF patients continued to receive intravenous antibiotics and/or oral
      vitamin preparations while being treated with opiates for terminal pain and
      dyspnea. Small doses of opiates seem to be effective in the treatment of the pain
      and dyspnea at the end of life in CF.

PMID- 9240801
TI  - Strategies to increase adherence with tuberculosis test reading in a high-risk
      population.
AB  - OBJECTIVE: To determine the most effective strategy to encourage adherence with
      tuberculosis test reading in a high-risk population. Design. Prospective
      randomized controlled trial. SETTING/PARTICIPANTS: Consecutive sample of 627
      children ages 1 to 12 years due for a tuberculosis (TB) test in an urban
      children's hospital outpatient department. One child per family was enrolled.
      INTERVENTION: All families received education regarding the importance of skin
      testing for TB and the need for follow-up, and written and verbal instructions
      regarding test reading. Families were randomly assigned to one of five strategies
      for follow-up TB test reading at 48 to 72 hours: 1) routine verbal and written
      instructions, 2) reminder phone call, 3) transportation tokens and toy on return,
      4) withholding of school forms until time of reading and need to repeat TB test
      if not timely read, 5) parents taught to read induration with nurse home visit.
      Those who did not have tests read at 48 to 72 hours by a trained professional
      were phoned 1 week later. RESULTS: The five groups did not differ with regard to
      TB risk factor score, maternal education, transportation source, or perceived
      importance of TB testing. Before the study the follow-up rate of TB test reading
      by a trained professional was 45%. Reading rates in this study were 58%, 70%,
      67%, 70%, and 72% for groups 1 to 5, respectively. In group 4, only 39% had
      school forms to be completed and their adherence rate was 84% (53/63). Compared
      to group 1, the only statistically significant improvement was in group 4,
      especially for those who needed school forms completed, and in group 5. Those not
      adhering in groups 1 to 4 did not differ from returnees with regard to TB risk
      factors, maternal education, transportation, or perceived importance of testing.
      The most common reasons for failing to return included forgetfulness,
      transportation, and time constraints. Group 5 was stopped early because of
      difficulty with nurse visits (N = 98). When told of the nurse visit, 9% (9/98)
      families could not find a time for the visit. Seventeen percent (17/98) were
      visited but the child was not home, and 7% (7/98) were not visited because of a
      nurse scheduling problem. CONCLUSIONS: In a high-risk population, adherence with
      TB test reading is poor. However, education and return of school forms at reading
      time can significantly improve adherence. Although requiring larger investment in
      resources, visiting nurses may also aid in test reading.

PMID- 9240802
TI  - Bedsharing promotes breastfeeding.
AB  - OBJECTIVE: Because breastfeeding is thought to be protective against sudden
      infant death syndrome (SIDS), environmental or child care factors that promote
      breastfeeding might reduce infant vulnerability to SIDS. The effect of mother
      infant bedsharing on nocturnal breastfeeding behavior was studied in 20 routinely
      bedsharing and 15 routinely solitary sleeping Latino mother-infant pairs when the
      infants were 3 to 4 months old. METHODOLOGY: All pairs were healthy and
      exclusively breastfeeding at night. The videotape portion of all-night laboratory
      polysomnographic studies was used for the analyses. For each pair, an adaptation
      night was followed by one night each of bedsharing and solitary sleeping.
      RESULTS: The most important finding is that when tested in their usual sleeping
      conditions, routinely bedsharing infants breastfed approximately three times
      longer during the night than infants who routinely slept separately: this
      reflected a two-fold increase in the number of breastfeeding episodes and 39%
      longer episodes. Breastfeeding was also facilitated on the bedsharing night
      relative to the solitary night within the routinely bedsharing group: the number
      and total duration of breastfeeding episodes were significantly larger on the
      bedsharing night. CONCLUSIONS: We suggest that, by increasing breastfeeding,
      bedsharing might be protective against SIDS, at least in some contexts.
      Furthermore, maternal reproductive physiology could be impacted because nursing
      frequency affects ovulation. This is the first study to directly measure
      nocturnal breastfeeding behavior in any cultural group.

PMID- 9240803
TI  - Psychiatric symptoms in preadolescents with musculoskeletal pain and
      fibromyalgia.
AB  - OBJECTIVES: To study the association of musculoskeletal pain with emotional and
      behavioral problems, especially depressive symptoms in Finnish preadolescents.
      STUDY DESIGN: A structured pain questionnaire was completed by 1756 third- and
      fifth-grade schoolchildren for identifying children with widespread pain (WSP),
      children with neck pain (NP), and pain-free controls for the comparative study.
      There were 124 children with WSP (mean age, 10.7 years), 108 children with NP
      (mean age, 11.1 years), and 131 controls (mean age, 10.7 years) who completed the
      Children's Depression Inventory (CDI) and a sleep questionnaire. A blinded
      clinical examination was done to detect fibromyalgia. For parental evaluation,
      the Child Behavior Checklist and a sociodemographic questionnaire were used. For
      teacher evaluation the Teacher Report Form was used. RESULTS: Children with WSP
      had significantly higher total emotional and behavioral scores than controls,
      according to child and parent evaluation. A significant difference in the mean
      total CDI scores was also found between the WSP and NP groups. Children with
      fibromyalgia had significantly higher CDI scores than the other children with
      WSP. CONCLUSIONS: Musculoskeletal pain, especially fibromyalgia, and depressive
      symptoms had high comorbidity. Pain and depressive symptoms should be recognized
      to prevent a chronic pain problem.

PMID- 9240804
TI  - Urinary incontinence and urinary tract infection and their resolution with
      treatment of chronic constipation of childhood.
AB  - OBJECTIVES: To evaluate the frequency of urinary incontinence and urinary tract
      infection in children with chronic constipation and report on the resolution of
      these with treatment of the underlying constipation. METHODS: We evaluated the
      frequency of urinary incontinence and urinary tract infection in 234 chronic
      constipated and encopretic children before, and at least 12 months after, the
      start of treatment for constipation. RESULTS: Twenty-nine percent complained of
      daytime urinary incontinence and 34% of nighttime urinary incontinence. Urinary
      tract infection was present in 11% and was more commonly present in girls than in
      boys (33% vs 3%). Vesicoureteral reflux was present in four and megacystis in
      four of the 25 children who had a voiding cystourethrogram because of urinary
      tract infection. One girl who came in had constipation and acute urinary
      retention. The treatment for constipation consisted of disimpaction and
      maintenance treatment, which included the prevention of reaccumulation of stools
      and reconditioning to normal bowel habits through timed toilet sitting. Follow
      up, at least 12 months after start of treatment for constipation, revealed that
      the constipation was relieved successfully in 52%. Relief of constipation
      resulted in disappearance of daytime urinary incontinence in 89% and nighttime
      urinary incontinence in 63% of patients, and disappearance of recurrent urinary
      tract infections in all patients who had no anatomic abnormality of the urinary
      tract. CONCLUSION: Urinary symptoms were found in a significant number of
      children who had functional constipation and encopresis. With treatment of the
      constipation, most patients became clean and dry and further recurrence of
      urinary tract infections was prevented.

PMID- 9240805
TI  - Efficacy of beta2-agonists in bronchiolitis: a reappraisal and meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy of beta2-agonists in bronchiolitis. DESIGN:
      Critical review and meta-analysis of randomized controlled trials of inhaled
      beta2-agonists. RESULTS: Three inpatient and five outpatient studies were
      identified. Inpatient studies (82 patients) were characterized by wide
      variability in therapeutic regimens and measurement of outcomes. Several problems
      were identified in the selection and specification of patients, such as failure
      to assess the prestudy duration of illness or to exclude patients already taking
      bronchodilators. Meta-analysis was not possible for inpatient trials due to the
      great variability in study outcomes, timing of outcome assessment, and drug
      regimens. Results of inpatient trials were contradictory: one found significant
      reductions in the clinical score and a shorter hospital stay with treatment,
      whereas two others found only significant oxygen desaturations. Outpatient
      studies (251 patients) examined immediate changes in physiologic measures and
      clinical scores after two treatments, but have not examined the effects of the
      longer-term regimen customarily used by clinicians. Meta-analysis revealed that
      short-term beta2-agonist therapy had no impact on the hospitalization rate or
      respiratory rate, and had a statistically significant but clinically
      insignificant impact on oxygen saturation and heart rate. The diversity of
      scoring systems precluded pooling of clinical score data. CONCLUSIONS: Despite
      eight clinical trials, conclusive evidence for the efficacy of beta2-agonist
      therapy for bronchiolitis remains unavailable. Well-designed inpatient trials are
      needed. Meta-analysis of outpatient studies does not support the use of beta2
      agonist therapy for bronchiolitis, but investigators have not studied the
      outcomes and the long-term outpatient regimen customarily used by clinicians.

PMID- 9240806
TI  - The effects of nutrient fortification and varying storage conditions on host
      defense properties of human milk.
AB  - OBJECTIVE: Data are scarce regarding the effects of nutrient fortification and
      storage on the immunoprotective properties of human milk. These effects are
      important considerations when feeding premature infants. We hypothesized that
      total bacterial colony counts (TBCC) and immunoglobulin A (IgA) concentration
      were not affected by the addition of fortifier even when tested under extreme
      storage conditions and that osmolality of fortified human milk does not increase
      with storage. METHODS: Ten frozen and five fresh milk samples from mothers of
      premature infants were divided into fortified and unfortified milk, and stored
      for 72 hours at either refrigerator or room temperature. Aliquots were obtained
      at 0 to 72 hours for TBCC, osmolality, and total IgA, and analyzed by repeated
      measures analysis of variance (ANOVA). RESULTS: Log10 TBCC in milk stored at
      refrigerator temperature for 0, 24, 48, and 72 hours were significantly greater
      in fortified vs unfortified milk; both increased similarly with storage.
      Osmolality was greater in fortified than unfortified milk; both increased by
      approximately 4% with storage. IgA concentration was not affected by
      fortification or storage. To simulate the usual nursery use of fortified human
      milk, a separate evaluation was performed. Fortified milk was stored at
      refrigerator temperature for 20 hours, warmed in a 40 degrees C laboratory
      incubator for 20 minutes, and placed in a 34 degrees C infant incubator for 4
      hours. Samples for TBCC were obtained at 0, 20, and 24 hours and analyzed by
      repeated measures ANOVA. Log10 TBCC in fortified, refrigerated milk did not
      change over the 20-hour storage but increased during the simulated 4-hour usage.
      CONCLUSIONS: These findings may warrant consideration when using human milk in
      the neonatal nursery but support recommendations to use commercially fortified
      human milk within 24 hours.

PMID- 9240808
TI  - Carbon monoxide and bilirubin production in neonates.

PMID- 9240809
TI  - Immunoprophylaxis and the control of respiratory syncytial virus disease.

PMID- 9240807
TI  - A review of psychosocial interventions for children with chronic health
      conditions.

PMID- 9240810
TI  - From both sides now: a parent-physician's view of parent-doctor relationships
      during pediatric cancer treatment.

PMID- 9240811
TI  - Let the user beware: specificity and sensitivity limits for in vitro diagnostic
      devices.

PMID- 9240812
TI  - Chronic fatigue syndrome should not be diagnosed in children.

PMID- 9240824
TI  - Contact lenses and microbial keratitis.

PMID- 9240825
TI  - Automated compensation of defocusing errors in videokeratography.
AB  - PURPOSE: The reproducibility of videokeratography measurements is mainly
      dependent on the accuracy of manual adjustment in the focal plane.
      Videokeratoscopes having small Placido cones show a considerable amount of error
      when the required working distance between cornea and keratoscope is not
      maintained. The advantages of small cones (optimal illumination and the reduction
      of anatomically caused shadows) are in no proportion to the disadvantage-poor
      depth of focus, resulting in poor reproducibility. METHODS: The Tubingen Color
      Ellipsoid Topometer compensates with software and hardware for defocusing errors
      by means of a triangulation measurement. An 8.0 mm sphere (42 D) was measured in
      a distance range of +/- 1.5 mm around the focal plane with and without
      compensation. Five measurements were acquired at each position to evaluate the
      reproducibility of the calculated data. RESULTS: Defocusation in the range of +/
      1.5 mm leads to deviation smaller than 0.05 mm (0.25 D). Without compensation,
      the maximal deviation is increased up to 0.7 mm (3.0 D), and thus is considerably
      greater. DISCUSSION: Automated compensation of defocusing errors in
      videokeratography actively compensates for defocusation errors, enhancing
      precision and avoiding measuring artifacts.

PMID- 9240826
TI  - The annular tinted contact lens syndrome: corneal topographic analysis of ring
      shaped irregular astigmatism caused by annular tinted contact lenses.
AB  - PURPOSE: Irregular corneal astigmatism has been reported in association with
      annular tinted hydrogel contact lenses. We report the abnormal videokeratographic
      findings of five patients wearing annular tinted contact lenses, who presented
      with bilateral blurred vision and revealed a loss of best corrected visual
      acuity. METHODS/RESULTS: The corneal topographic analysis revealed a previously
      unreported distinct ring-shaped pattern of irregular astigmatism. The topographic
      circular band of irregular astigmatism was further characterized by concentric
      areas of relative steepening, flattening, and steepening with a diameter of
      approximately 4 mm. This pattern suggests that forces acting at the junctional
      zone between the tinted area and the clear pupillary area are inducing structural
      abnormalities of the corneal surface. At the time of presentation, the mean
      surface regularity index (SRI) was 2.06 (range: 0.61-5.88). The topography and
      best-corrected visual acuity returned to normal within days of discontinuing
      annular tinted lens use, and the mean SRI decreased to 0.44 (range: 0.21-1.16).
      Digital imaging of lenses obtained from our patients and of identical control
      lenses was performed. A masked analysis suggested that the study lenses contain
      greater amounts of pigment compared to the control lenses. CONCLUSIONS: We
      present ten characteristic signs and symptoms of this condition, which we have
      named "the annular tinted contact lens syndrome." Corneal topographic analysis is
      a powerful tool for detecting specific reversible irregularities of the corneal
      surface associated with the use of annular tinted contact lenses.

PMID- 9240827
TI  - The evaluation of normal corneal topography in emmetropic eyes with computer
      assisted videokeratography.
AB  - PURPOSE: By defining the topographic features of normal corneas, corneal surface
      abnormalities and their relation to visual function may be better understood. In
      our study, we have defined the corneal topographic features of emmetropic eyes to
      evaluate the relationship between topographic patterns and visual acuity.
      METHODS: Topographic pattern of 114 normal corneas of 114 emmetropic subjects
      with a keratometric astigmatism of 0.5 D or less were analyzed by computer
      assisted videokeratography. Thetopographic maps were grouped into the following
      patterns: round, oval, symmetric bow tie, asymmetric bow tie, and irregular.
      RESULTS: Asymmetric bow tie was the most common topographic pattern in our study
      population (33%), followed by symmetric bow tie (29%), round (14%), irregular
      (12%), and oval (11%) patterns. There were significant differences in the
      astigmatic values obtained by keratometry versus videokeratography for aspheric
      patterns, while the values among the spheric patterns were more in agreement.
      Mean corneal astigmatism calculated from videokeratographic data was 0.24 D for
      round, 0.61 D for oval, 1.05 D for symmetric bow tie, 0.85 D for asymmetric bow
      tie, and 0.76 D for irregular patterns. CONCLUSION: We conclude that: the
      topographic configuration may not be a good predictor of visual function; an
      emmetropic eye may have an aspheric topographic pattern, such as asymmetric or
      symmetric bow tie; and the reconstruction algorithm used for providing
      topographic maps may not be accurate enough to determine the true shape of the
      corneal surface for interpretation.

PMID- 9240828
TI  - Current recommendations and practice regarding soft lens replacement and
      disinfection.
AB  - PURPOSE: We evaluate contact lens wearers' compliance with practitioner
      recommendations through the analysis of survey data. Trends in practitioner
      recommendations on discarding intervals and frequency of disinfection for soft
      contact lenses are analyzed and compared to actual wearer usage. METHODS: The
      results of two primary surveys are used. One survey measures fit and wear
      recommendations for contact lens patients by eyecare providers during 1994 and
      1995. The second survey was conducted at the end of 1995 to ascertain contact
      lens wearers' practices in contact lens wear and care. RESULTS: The general trend
      in practitioner recommendations is towards either disposable or frequent
      programmed replacement intervals coupled with daily disinfection. Approximately
      15% of the brands marketed for disposable use were recommended for replacement at
      intervals longer than two weeks--the longest interval associated with disposable
      lenses. We observe a discrepancy between practitioner recommendations and the
      lens care provided by patients, noting a tendency to replace lenses at intervals
      longer than recommended. CONCLUSIONS: Trends in practitioner recommendations are
      consistent with expectations of providers. However, the observation that patients
      tend to increase their discarding intervals implies that practitioners could do
      better in educating their patients as to discarding intervals and in prescribing
      products that best match patient needs for both convenience and cost. These data
      should alert contact lens fitters to the importance of giving clear instructions
      to patients on how they should wear and care for contact lenses.

PMID- 9240829
TI  - A technique for quantitation of protein deposits on rigid gas permeable contact
      lenses.
AB  - PURPOSE: The purpose of this study was to develop a method for quantitating
      protein on rigid gas permeable (RGP) lenses and apply it to worn lenses. METHODS:
      We built a video microscope and wrote software to measure light absorbance by
      contact lenses before and after protein staining with Coomassie brilliant blue.
      We corrected for the temporal stability and spatial uniformity of the system, and
      set the iris aperture so that both lens surfaces could be simultaneously focused.
      We examined four RGP lens types worn by 22 patients. Standard curves were
      prepared with plastic discs spiked with dialyzed Coomassie blue-stained bovine
      serum albumin. RESULTS: The method was linear (R2 = 0.99) from 14 to over 100
      microg protein per image and independent of dioptric power from -6 to +14
      diopters. Protein quantities on worn Equalens II, Advent, Quantum II, and
      Fluoroperm 92 lenses were not significantly different (123 +/- 36, 111 +/- 28,
      110 +/- 23, and 83 +/- 15 microg/lens; means +/- SEMs, P > 0.7). Patients
      differed (P < 0.05) in protein deposition, independently of lens type, and fit a
      Poisson distribution. DISCUSSION: The method is adequate for quantitating protein
      on RGP lenses or for examining the efficacy of cleaning regimens or care systems.
      However, because of the non-Gaussian distribution of patient protein deposits,
      paired or cross-over experimental design and testing is recommended for studying
      protein deposition in clinical trials.

PMID- 9240830
TI  - The effect of high and low Dk/L soft contact lenses on the glycocalyx layer of
      the corneal epithelium and on the membrane associated receptors for lectins.
AB  - PURPOSE: Bacterial adherence or binding to the target cell is a prerequisite for
      the initial stage of most infections and seems to be mediated by lectin-like
      ligands on the bacterial surface and specific receptors on the target cell
      membrane. The purpose of this study was to establish whether contact lens wear
      under closed eye conditions changes the glycocalyx layer, whether it exposes more
      lectin receptors than eye closure without a contact lens, and whether wear of low
      oxygen transmissibility (Dk/L) contact lenses exposes more receptors than high
      Dk/L contact lenses. METHODS: The eyes of six rabbits under general anesthesia
      were fit with either a high Dk/L soft contact lens (40 x 10(-9), boundary
      corrected) or a low Dk/L soft contact lens (2 x 10[-9]) or were left without a
      lens as controls. All eyes were kept closed by suturing for 24 hours. After
      removal of the contact lenses, all corneas were excised, put in
      glutaraldehydeforfixation, rinsed, incubated with plant-derived lectins (wheat
      germ agglutinin [WGA]) conjugated with gold particles, and prepared for electron
      microscopy. Membrane associated gold particles were counted and the results were
      processed statistically. RESULTS: After 24 hours of lens wear under closed eye
      conditions, the glycocalyx layer showed physical changes in the form of thinning
      or compression and signs of biochemical changes reflected as an increase in
      number of WGA receptors. The average number of membrane associated gold particles
      per 750 micro length of corneal epithelium in control corneas was 1,287.5 +/-
      92.5. Particles were significantly (P<0.001) more numerous after wear of high
      Dk/L contact lenses (3,230.0 +/- 294.5) and after wear of low Dk/L contact lenses
      (4,611.3 +/- 223.3). The figure after wear of low Dk/L contact lenses was
      significantly (P<0.01) higher than the figure after wear of high Dk/L contact
      lenses. CONCLUSION: Our results indicate that lens wear under closed eye
      conditions seems to change the corneal glycocalyx layer physically as well as
      biochemically. Significantly larger numbers of WGA receptors were exposed after
      contact lens wear than without a contact lens. Significantly more receptors were
      exposed after wear of low Dk/L contact lenses than after wear of high Dk/L
      contact lenses. These changes may be of importance in relation to the risk of
      bacterial keratitis.

PMID- 9240831
TI  - Contact lens use after contact lens-associated infectious ulcers.
AB  - PURPOSE: The purpose of this study was to evaluate the outcome of patients with
      healed moderate to severe contact lens-associated corneal infectious ulcers who
      were re-fit with contact lenses. METHODS: We retrospectively studied patients who
      were fit with contact lenses on our service and who had had moderate to severe
      corneal infectious ulcers associated with previous contact lens use. Six patients
      were included in the study. RESULTS: Gas permeable contact lenses were fit in
      five patients, and a soft contact lens was fit in one patient. Successful fit was
      achieved in all cases and visual acuities were equal to or better than 20/30 in
      all patients. No significant complications were observed after a mean follow-up
      of 23 months (range, 6-45 months). CONCLUSION: In this small series of patients
      with a history of moderate to severe contact-lens related infectious keratitis,
      no complications were observed after contact lenses were refit. Contact lens wear
      in patients with a history of infectious keratitis may be safe and useful in
      order to achieve visual rehabilitation.

PMID- 9240832
TI  - Ultraviolet radiation revisited.
AB  - PURPOSE AND METHODS: It is likely that we currently receive a greater lifetime
      exposure to ultraviolet radiation (UVR) than earlier generations due to increased
      UVR reaching the earth's surface, our longer life expectancy, and increased
      activities in UV intense environments. This elevated UVR exposure is likely to
      lead to a higher incidence of acute and chronic ocular and skin radiation trauma.
      We reviewed the evidence in the current literature supporting these assertions as
      well as reports of preventive strategies for blocking UVR. RESULTS: Hawaii is the
      most UV-intense location on earth as it has the lowest ozone thickness values
      ever recorded outside the Antarctic zone. It is anticipated that the overall
      ozone depletion will continue into the next millennium. Significant evidence
      suggests a correlation between UVR exposure and conjunctival pterygium,
      photokeratitis, climatic droplet keratopathy and cataracts. The incidence of skin
      cancer is also on the rise as a result of the increased amount of UVR reaching
      the earth secondary to the thinning ozone. CONCLUSIONS: There are compelling
      reasons to counsel our patients on the adverse effects of UVR and to offer them
      the various options available for UV protection. Sunglasses and UV blocking
      ophthalmic lenses traditionally have been the most commonly selected forms of UVR
      protection. The UV blocking hydrogel contact lens, a recent addition to our
      armamentarium, is a means of blocking UVR.

PMID- 9240833
TI  - Complications of combined radial thermokeratoplasty and incisional keratotomy.
AB  - PURPOSE: To report complications of radial thermokeratoplasty (RTK) when used in
      combination with either radial keratotomy (RK) or astigmatic keratotomy (AK).
      METHODS: RTK is a technique for the surgical correction of hyperopia and
      presbyopia. 600 degrees C burns are applied to the peripheral cornea for 0.3
      seconds using a specialized cautery probe. The thermal energy generated shrinks
      stromal collagen and flattens the peripheral cornea. The central cornea is
      steepened producing a myopic shift. RESULTS: Two patients who had RTK in
      combination with either RK or AK are reported. Patient 1 was bilaterally
      hyperopic and presbyopic. The patient had RTK performed on the left eye in an
      attempt to make that eye myopic. The goal was to allow the left eye to be used
      for near vision. After RTK, the left eye was significantly overcorrected. The
      patient then had RK in the left eye which resulted in profound overcorrection
      with return of hyperopia. Postoperatively, examination revealed gaping of the RK
      incisions and poor epithelial wound healing. The patient also complained of
      severe ocular pain. Despite suturing the RK incisions, the eye remained
      hyperopic. The patient underwent two additional RTK procedures which failed to
      correct the induced hyperopia. The second patient had induced hyperopic
      astigmatism after undergoing RK. RTK was then performed to correct the hyperopia.
      However, the result was a worsening of the astigmatism. Two t-cut astigmatic
      keratotomies were then performed which improved the astigmatism but subsequently
      exacerbated the hyperopia. A second RTK procedure was then performed; however, it
      failed to correct the induced hyperopia. CONCLUSIONS: RTK is an unproved surgical
      technique for the correction of hyperopia and presbyopia that needs much further
      evaluation before broad clinical application can be supported.

PMID- 9240835
TI  - Light microscopic, immunohistochemical, and electron microscopic features of
      amyloid arthropathy in chickens.
AB  - Amyloid arthropathy has been recently recognized as a spontaneous syndrome in
      chickens. Predominantly, femorotibial and tarsometatarsal joints were affected,
      showing (peri) articular orange amyloid deposits. Immunohistochemical evaluation
      revealed the amyloid to be of the reactive type. Induction of amyloid arthropathy
      in chickens was carried out using a single intravenous injection of Enterococcus
      faecalis cultures. In the naturally occurring and the induced cases, amyloid
      deposits were found in the hypertrophic synovial villi and in the articular
      cartilage, particularly in the superficial layer and in the nutritional blood
      vessel walls. Highly sulfated glycosaminoglycans (GAGs) were found in the amyloid
      deposits. Ultrastructurally, bundles of amyloid fibrils were seen in
      invaginations of synoviocytes and chondrocytes. Immunogold electron microscopy
      failed to reveal signs of intracellular amyloid formation. The predilection site
      for amyloid deposition in the major leg joints of the chickens with reactive
      amyloid could be explained by the arthritic condition caused by Enterococcus
      faecalis bacteriaemia. The polyarthritis triggers hepatic acute phase protein
      synthesis and increases the vascular serum amyloid A (SAA) supply to the joint.
      Inflammatory and degenerative changes in the articular cartilage and adjoining
      tissues result in an increase of highly sulphated GAGs, which are considered to
      enhance deposition of SAA as amyloid.

PMID- 9240834
TI  - Pathogenicity of cilia-associated respiratory (CAR) bacillus isolates for F344,
      LEW, and SD rats.
AB  - We conducted experiments to test whether rats of F344, LEW, and SD strains differ
      in susceptibility to mycoplasma-free isolates of cilia-associated respiratory
      (CAR) bacillus, whether Mycoplasma pulmonis can affect expression of CAR bacillus
      disease, and whether isolates of CAR bacillus differ in virulence for rats. In
      the first experiment, 24 rats of each strain were inoculated intranasally with
      10(7) bacilli of CAR bacillus X1428D/AS, and 24 rats of each strain were
      inoculated with sterile medium (controls). Eight weeks later, eight inoculated
      rats and eight control rats of each strain were euthanatized, eight inoculated
      and eight control rats were given 10(6.5) colony-forming units of M. pulmonis
      X1428D, and eight inoculated rats and eight control rats were sham inoculated.
      Four rats of each group were euthanatized 4 or 8 weeks after the second
      inoculation. Severity of lesions in nasal passages, middle ear, trachea, and
      lungs was assessed by scoring. Rats of all three strains given CAR bacillus had
      typical lesions of similar severity; M. pulmonis X1428D was avirulent and did not
      exacerbate CAR bacillus disease. In the second experiment, groups of eight rats
      of F344 and SD strains were given 10(5) or 10(7) CAR bacillus X1328E, X1428D/AS,
      or X2450D and euthanatized 8 or 16 weeks later. Isolates X1428D/AS and X2450D
      caused similar lesions in rats of both strains and at both doses, but CAR
      bacillus X1328E was avirulent. Rats of the tested strains are similarly
      susceptible to CAR bacillus disease, but CAR bacillus isolates differ in
      virulence.

PMID- 9240836
TI  - A prospective study of the immunophenotype and temporal changes in the histologic
      lesions of canine demodicosis.
AB  - Mural folliculitis is a consistent histologic lesion of canine demodicosis. The
      objective of this study was to describe the immunophenotype and to evaluate
      temporal changes in histologic lesions of demodicosis during the course of
      therapy. Five dogs with demodicosis were examined and biopsied biweekly for up to
      14 weeks; three dogs were evaluated once only. Lymphocyte subsets infiltrating
      the lesions were quantified using immunohistochemistry to detect CD3, CD21, CD4,
      and CD8 antigens. Lymphocyte subsets in blood were analyzed from four dogs using
      flow cytometry. Mural folliculitis was always present during clinically active
      disease. In contrast, following resolution of clinical lesions, perifolliculitis
      and/or perifollicular granulomas were present but mural folliculitis was absent.
      Most lymphocytes infiltrating the follicular epithelium in lesions of mural
      folliculitis were CD3+ and CD8+; the ratio of CD4+ :CD8+ cells in this epithelium
      was 0.032. In contrast, the perifollicular dermis contained approximately equal
      numbers of CD4+ cells and CD8+ cells, with slightly fewer CD21+B cells. In
      peripheral blood, the ratio of CD4+:CD8+ lymphocytes was reduced and the
      percentage of CD8+ cells was increased in three of four dogs. These results
      indicate that mural folliculitis is a consistent lesion of clinically active
      canine demodicosis and is characterized by infiltration of the follicular
      epithelium by CD3+ CD8+ T lymphocytes. These lymphocytes are cytotoxic T cells,
      which may mediate the injury to the follicular epithelium in demodicosis.
      Alternatively, CD8+ T cells may play a role in resistance to Demodex canis
      infection or may represent a deleterious immune response in dogs that develop
      demodicosis.

PMID- 9240838
TI  - Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs.
AB  - With the recent epizootic of bovine spongiform encephalopathy in Europe, the
      differential diagnosis of neuronal vacuolation and spongiform change in other
      species has become critically important. Four Rottweiler puppies of both sexes,
      presented at 3-8 months of age, had clinical signs of generalized weakness and
      ataxia that started at 6 weeks of age. In all pups, neurologic examination
      detected an ataxia and tetraparesis, most severe in the pelvic limbs, and slowed
      proprioceptive placing reactions. Subsequently, there was rapid progressive
      neurologic deterioration, with severe placing deficits, knuckling, severe ataxia,
      and quadraparesis by 8 months of age. At necropsy, no gross lesions were
      observed. Microscopic lesions were restricted to the nervous system. The major
      lesion in all dogs was an intracytoplasmic neuronal vacuolation that was most
      prominent in the cerebellar roof nuclei and in nuclei of the extrapyramidal
      system. Similar vacuolation was found in neurons in both dorsal nerve root
      ganglia, myenteric plexus, and other ganglia of the autonomic nervous system. The
      single or multiple empty vacuoles were between 1 and 45 microm in diameter. A
      mild spongiform change was seen in the adjacent neuropil. Purkinje cell
      vacuolation and degeneration with segmental cell loss was seen in the oldest dog.
      In ventromedial and dorsolateral areas of the spinal cord white matter, there was
      mild bilaterally symmetrical axonal degeneration. Immunoblotting and
      immunocytochemical staining of the brain for protease-resistant scrapie prion
      protein was negative. All forms of vacuoles were negative for immunohistochemical
      staining with a variety of lectins. Ultrastructurally, the vacuoles were bound by
      a single membrane and contained granular material and sometimes membranous
      profiles. There was mild distension of the cytocavitary network but no
      unequivocal connection with the vacuoles was found. Axosomatic and axodendritic
      synapses in affected neurons were intact both ultrastructurally and with
      synaptophysin immunostaining. The clinicopathologic findings were different from
      those seen in the other neurologic diseases of Rottweilers. The age of the dogs,
      distribution and type of the lesions, ultrastructural findings, and negative
      immunoblotting most likely rule out the possibility of a scrapie agent-associated
      spongiform encephalopathy. However, the etiology of this new disease was not
      determined.

PMID- 9240837
TI  - Histologic, immunohistochemical, and polymerase chain reaction studies of
      bottlenose dolphins from the 1987-1988 United States Atlantic coast epizootic.
AB  - Tissues from 95 bottlenose dolphins (Tursiops truncatus) that died during the
      1987-1988 US Atlantic coast epizootic and 11 bottlenose dolphins that died along
      the Atlantic coast prior to 1987 were examined histologically and
      immunohistochemically. Polymerase chain reaction (PCR) testing was performed on
      36 of the epizootic and all of the pre-1987 cases. Epizootic cases had syncytia
      and rare intranuclear and intracytoplasmic inclusion bodies within lung, lymph
      node, and spleen. Lymphoid depletion was present in lymph node, spleen, and gut
      associated lymphoid tissue of epizootic cases. Pre-1987 cases did not have these
      pulmonary and lymphoid lesions. A larger percentage of epizootic than pre-1987
      cases had bacterial and/or fungal infections (primarily pneumonias), pulmonary
      and lymphoid tissue histiocytosis, mucocutaneous ulcers, and evidence of negative
      energy balance. Immunohistochemically, 49/95 (52%) epizootic dolphins were
      positive for morbilliviral antigen. Morbilliviral antigen was detected in lung,
      lymph node, spleen, thymus, skin, tongue, esophagus, liver, pancreas,
      gastrointestinal tract, urinary bladder, oviduct, and mammary gland by
      immunohistochemistry. PCR testing identified morbilliviral RNA in 35/36 (97%)
      epizootic cases tested. Neither morbilliviral antigen nor morbilliviral RNA were
      detected in pre-1987 cases. Histologic, immunohistochemical, and PCR results
      provide strong evidence that morbillivirus infection was the primary cause of the
      1987-1988 bottlenose dolphin epizootic.

PMID- 9240839
TI  - Immunohistochemical staining characteristics of canine gastrointestinal stromal
      tumors.
AB  - Sections from 35 formalin-fixed, paraffin-embedded, canine gastrointestinal
      stromal tumors consisting of 14 leiomyomas (five stomach, three small intestine,
      two colon, four rectum), 18 leiomyosarcomas (one stomach, five small intestine,
      nine cecum, three rectum), two undifferentiated sarcomas (two stomach), and one
      neurofibrosarcoma (small intestine) were examined for the expression of vimentin,
      S-100 protein, alpha-smooth muscle actin, and desmin via immunoperoxidase
      methodology using an avidin-biotin complex technique. The leiomyomas were 4/14
      (29%) vimentin-positive, 3/14 (21%) S-100 protein-positive, 10/14 (71%) alpha
      smooth muscle actin-positive and 13/14 (93%) desmin-positive. Leiomyosarcomas
      were 18/18 (100%) vimentin-positive, 11/18 (61%) S-100 protein-positive, 9/18
      (50%) a-smooth muscle actin-positive, and 15/18 (83%) desmin-positive. The
      undifferentiated sarcomas were 2/2 (100%) vimentin-positive, 2/2 (100%) S-100
      protein-positive, 1/2 (50%) alpha-smooth muscle actin-positive, and 0/2 (0%)
      desmin-positive. The neurofibrosarcoma was vimentin and S-100 protein-positive
      and alpha-smooth muscle actin- and desmin-negative. Thirty-one of thirty-five
      (89%) of all neoplasms demonstrated reactivity for either desmin and/or alpha
      smooth muscle actin. S-100 protein reactivity occurred in 17/35 (49%) of all
      specimens. Lack of desmin and alpha-smooth muscle actin reactivity occurred in
      4/35 (11%) of all specimens, all of which were vimentin-positive. The
      immunohistochemical results indicate that the majority of canine gastrointestinal
      stromal tumors (GIST) with light microscopic features of smooth muscle cells have
      immunohistochemical staining patterns supporting smooth muscle differentiation.
      Vimentin reactivity correlated with a light microscopic diagnosis of malignancy.
      The lack of smooth muscle cell markers in some tumors and the high percentage of
      cases positive for S-100 protein may suggest a more complex histogenesis or
      differentiation for subgroups of these tumors.

PMID- 9240840
TI  - Lesions of experimental equine morbillivirus pneumonia in horses.
AB  - Laboratory examinations of equine morbillivirus included experimental
      reproductions of the disease caused by the virus by transmission of mixed lung
      and spleen taken from two field equine cases into two horses and by inoculating
      tissue culture virus into a further two horses. The most distinctive gross
      lesions of the diseases that developed in three of the horses was that of
      pulmonary edema characterized by gelatinous distension of subpleural lymphatics.
      Histologically, the lesions in the lungs were those of serofibrinous alveolar
      edema, alveolar macrophages, hemorrhage, thrombosis of capillaries, and syncytial
      cells. Clearly defined vascular lesions in three horses that became clinically
      affected within 8 days of inoculation of virus included intramural hemorrhage,
      edema, and necrosis and syncytial cells in the endothelium of pulmonary vessels
      (approximately 40-70 microm in diameter). Vascular lesions accompanied by
      parenchymal degeneration were also seen in the heart, kidney, brain, spleen,
      lymph node, and stomach. A fourth horse, which survived for 12 days, had
      detectable lesions only in the lungs, which were more chronic than those in the
      other three horses, a greater degree of cellular infiltration, and fewer well
      defined vascular lesions. Sections stained by an indirect immunocytochemical
      method showed equine morbillivirus antigen was present in the vascular lesions
      and along alveolar walls. When endothelial cells were examined by electron
      microscope, cytoplasmic virus inclusion bodies containing filamentous structures
      were seen that reacted to an immunogold test to equine morbillivirus antigen. The
      presence of the syncytia in the small blood vessels in the lungs and other organs
      was interpreted as an important characteristic of the disease and consistent with
      a reaction to a morbillivirus.

PMID- 9240841
TI  - The lesions of experimental equine morbillivirus disease in cats and guinea pigs.
AB  - Nine cats and four guinea pigs became affected with severe disease during
      experiments on the infectivity of equine morbillivirus, a newly recognized cause
      of respiratory disease in horses and humans. Four of the cats were challenged by
      subcutaneous inoculation, two by intranasal installation, two by oral dosage, and
      one by direct contact with a cat previously infected by subcutaneous inoculation.
      All four guinea pigs were inoculated subcutaneously. Gross pathology seen in all
      affected cats was characterized by hydrothorax and dark, heavy, wet, congested
      and/or hemorrhagic lungs with froth sometimes found in the respiratory passages.
      Pulmonary lymph nodes were enlarged and edematous. Six cats also had congested
      ceca with accompanying edema of mesenteric lymph nodes. Histologically, the
      lesions in the lungs of the cats were those of severe interstitial pneumonia
      characterized by serofibrinous alveolar edema, alveolar macrophages, intra
      alveolar hemorrhage, thrombosis of small veins, alveolar wall necrosis, and
      syncytial cells. Clearly defined vascular lesions included intramural hemorrhage,
      edema, and necrosis and syncytial cells in the endothelium of pulmonary arteries
      and veins, 20-80 microm in diameter. Vascular lesions accompanied by parenchymal
      degeneration were also seen in the gastrointestinal and lymphoid organs.
      Syncytial cells were also visible in the lymphoid tissues of lymph nodes, spleen,
      and Peyer's patches. At necropsy, all guinea pigs were cyanosed and had
      congestion and edema in the gastrointestinal tract. Histologically, there was
      widespread vascular disease in arteries and veins, 20-80 microm in diameter, in
      many organs such as the lungs, kidneys, spleens, lymph nodes, gastrointestinal
      tracts, and skeletal and intercostal muscles, but there was no severe pulmonary
      edema as seen in horses and cats. Sections of tissues of the cats and guinea
      pigs, examined by indirect immunocytochemical stains, confirmed that the vascular
      damage was associated with the presence of equine morbillivirus antigen. The
      syncytia in small blood vessels in the lungs and other organs of both cats and
      guinea pigs were similar to those seen in horses, and their presence was
      interpreted as an important characteristic of the disease consistent with a
      reaction to a morbillivirus.

PMID- 9240842
TI  - Experimentally induced selenosis of adult mallard ducks: clinical signs, lesions,
      and toxicology.
AB  - Selenosis is thought to be a significant problem among waterfowl populations in
      selenium-contaminated wetlands in the western United States. Chemical analysis of
      avian tissues is currently the principal basis for diagnosis. The purpose of
      these two 150-day studies was to establish whether morphological criteria for
      selenosis could be developed to supplement chemical analysis. Forty-eight
      flightling male mallard ducks were fed either a proprietary waterfowl ration (< 1
      ppm selenium) or the same ration amended to contain 10, 25, and 60 ppm selenium
      supplied as seleno-L-methionine (n = 12/group). In a separate study, 12 birds fed
      twice daily were offered either a proprietary ration or a selenium-supplemented
      ration (120 microg/g) for one of two daily feedings. Selenium in whole blood
      increased from baseline concentrations (< 0.4 microg/ml) to means of 4.5, 8.9,
      and 16.0 microg/ml in the 10-, 25-, and 60-ppm groups, respectively. All birds in
      the 60-ppm-dose group rapidly lost weight and were killed (11/12) or died (1/12)
      between 22 and 50 days of dietary exposure. In addition to emaciation, six of 12
      birds (50%) fed the 60-microg/g diet developed mild to moderate generalized
      hepatopathy with single-cell necrosis, karyomegaly of hepatocytes, hyperplastic
      bile duct epithelium, and/or iron accumulation in Kupffer cells. The principal
      lesions in birds exposed to other dietary concentrations of selenium involved
      integumentary structures containing hard keratin. Gross lesions developed after
      76 days of dietary exposure and consisted of bilaterally symmetrical alopecia of
      the scalp and dorsal cervical midline, broken or lost digital nails, and necrosis
      of the tip of the beak (maxillary nail). One or more of these three lesions were
      present in 0/12 birds (0%) fed 10 ppm selenium, 5/12 birds (42%) fed 25 ppm
      selenium, and 4/9 (44%) birds fed a split-feed diet containing 120 ppm selenium.
      Controls were unaffected. Histologic lesions in digital and maxillary nails
      consisted of single-cell to full-thickness necrosis of keratinocytes and
      multifocal parakeratosis in stratum corneum. Histologic lesions in alopecic skin
      (necrosis of the epidermal collar, inflammation of the feather pulp, and
      follicular keratosis) were mild. Some birds with alopecia had no detectable
      lesions in feather follicles from affected areas of skin. The highest tissue
      concentrations of selenium were in liver, kidney, and feathers, respectively.
      Mean hepatic tissue concentrations were 14.5 microg/g (10 ppm group), 29.6
      microg/g (25 ppm group), 60.6 microg/g (60 ppm group), 13.0 microg/g (120 ppm
      split-feed group), and 2.0 microg/g (controls). Integumentary and hepatic lesions
      may be of value in corroborating a diagnosis of selenosis based on chemical
      analysis of tissues from naturally intoxicated waterfowl. Some birds with fatal
      selenosis may have no morphologic lesions other than emaciation.

PMID- 9240843
TI  - Idiopathic myelofibrosis (agnogenic myeloid metaplasia) in a marmoset (Callithrix
      jacchus): hematologic and histopathologic changes.
AB  - Idiopathic myelofibrosis (IMF), or agnogenic myeloid metaplasia, was diagnosed in
      a sexually mature male marmoset (Callithrix jacchus) based on the results of
      hematology and histopathologic evaluation of the bone marrow. The hematologic
      changes included pancytopenia, leukoerythroblastosis, anisocytosis,
      poikilocytosis, and giant platelets. Histopathologic evaluation of the bone
      marrow showed marked widespread fibrosis replacing hematopoietic cells and the
      presence of atypical megakaryocytes. In addition, slight multifocal osteolysis
      with an increase in serum alkaline phosphatase activity was observed. We believe
      this is the first report of IMF in a nonhuman primate species.

PMID- 9240844
TI  - S-100 immunoreactivity in melanomas of the South American opossum Monodelphis
      domestica.
AB  - S-100 immunoreactivity was determined 1) in foci of melanocytic hyperplasia, 2)
      in naturally occurring, ultraviolet radiation-induced, and 9,10-dimethyl-1,2
      benzanthracene (DMBA)-induced primary melanomas, and 3) in metastatic melanoma
      lesions in the South American opossum Monodelphis domestica. Preneoplastic
      lesions of melanocytic hyperplasia contained scattered cells with S-100-positive
      nuclei. All primary melanomas, with the exception of a single DMBA-induced tumor,
      contained cells with S-100-positive nuclei. The pattern of S-100 reactivity in
      tumors varied from large foci of S-100-positive cells to scattered individual S
      100-positive cells. Lymph node metastases were S-100 positive, but metastatic
      masses in internal organs were usually S-100 negative. Although S-100 reactivity
      did not distinguish preneoplastic lesions from tumors or benign melanomas from
      malignant melanomas, identification of metastatic tumor cells clearly
      demonstrated malignancy.

PMID- 9240845
TI  - Trombidiosis-induced dermatitis in white-tailed deer (Odocoileus virginianus).
AB  - During a routine blood collection at a wildlife management checkpoint, several
      white-tailed deer (Odocoileus virginianus) from Lake Russell Wildlife Management
      Area, Habersham County, Georgia, were observed to have accumulations of orange
      granular material around the eyes and mouth accompanied by serous exudate,
      crusting, and alopecia. Microscopic examination of the granular material
      disclosed numerous larval mites of the family Trombiculidae. Histologic
      examination revealed severe chronic diffuse plasmacytic dermatitis with
      intralesional larval trombiculid mites. Several stylostomes were also identified
      in the tissue sections. This paper describes the gross and histologic changes
      associated with severe trombiculid infestation in a white-tailed deer and
      suggests potential causes for this unusual finding.

PMID- 9240846
TI  - Bilateral renal metastases of nasal chondrosarcoma in a dog.
AB  - Chondrosarcoma is the most common nonepithelial sinonasal neoplasm in the dog,
      and metastasis is considered rare. A 7-year-old Irish Setter had bilateral renal
      enlargement 17 months following surgery and radiotherapy for a primary nasal
      chondrosarcoma. Histologic evaluation revealed chondrosarcoma metastases in both
      kidneys. A diagnosis of nasal chondrosarcoma with bilateral renal metastasis was
      made. The clinical importance of this report is that routine recommendations for
      the evaluation of regional and/or distant metatasis in a dog with a dignosis of
      nasal chondrosarcoma, namely routine whole body physical examination and thoracic
      radiography, failed to demonstrate the presence of abdominal metatases, which
      ultimately led to the demise of this dog. The biologically aggressive nature of
      this chondrosarcoma of the nasal cavity indicates that additional information is
      needed before a prognosis can be reliably established for dogs with this tumor
      type.

PMID- 9240847
TI  - Immunohistochemical localization of parathyroid hormone-related protein in canine
      mammary tumors.
AB  - Parathyroid hormone-related protein (PTHrP) was localized immunohistochemically
      in 58 canine mammary tumors (31 malignant, 27 benign) and adjacent normal or
      hyperplastic mammary tissue. PTHrP immunoreactivity was significantly enhanced by
      pretreatment with microwave heating in normal and neoplastic tissues. Epithelial
      cells of hyperplastic and neoplastic mammary tissues, myoepithelial cells, and
      metaplastic osteoblasts in mammary tumors stained moderately to strongly positive
      for PTHrP No significant difference between staining intensity for PTHrP and
      histologic pattern of mammary tumors was found. The presence of PTHrP in normal
      and neoplastic canine mammary tissues supports a pathophysiological role for
      PTHrP as a paracrine or autocrine hormone in the mammary gland.

PMID- 9240848
TI  - Rhabdoid tumor in the brain of a dog.
AB  - Rhabdoid tumor is a neoplasm of uncertain cellular origin recognized in humans.
      These tumors most commonly arise in the kidneys of children, but they can also
      affect many extrarenal sites, including the central nervous system. Similar
      neoplasms have not been reported in nonprimate species. A malignant brain tumor
      in a young dog was characterized by large cells with globular intracytoplasmic
      inclusions composed of intermediate filaments. By immunohistochemistry,
      neoplastic cells were uniformly reactive for vimentin and demonstrated scattered
      reactivity for glial fibrillary acidic protein and neuron-specific enolase. The
      intermediate filaments also reacted with vimentin antibodies by immunogold
      electron microscopy. The findings in this case are remarkably similar to the
      histologic, ultrastructural, and immunocytochemical features of rhabdoid tumors
      in humans.

PMID- 9240849
TI  - Interaction between timing of perinatal human immunodeficiency virus infection
      and the design of preventive and therapeutic interventions.
AB  - In 1994, the hypothesis that transmission of human immunodeficiency virus (HIV)
      from mother to child could be interrupted became a reality when it was shown that
      a regimen of zidovudine given to HIV-infected pregnant women and their newborn
      infants could reduce the risk of perinatal transmission by two-thirds. An
      understanding of the pathogenesis of transmission is crucial for interpreting
      these results, for design of future interventions and for understanding the
      natural history of perinatal HIV infection. This paper will review current
      information regarding the timing of and risk factors for perinatal HIV
      transmission, and the relationship between the timing of transmission and design
      of efforts to interrupt transmission and to slow disease progression in infected
      infants.

PMID- 9240850
TI  - Pregnancy and HIV infection in Europe.
AB  - Human immunodeficiency virus (HIV) seroprevalence among pregnant women varies
      between and within countries and is generally higher in urban than in rural
      areas. In the European Collaborative Study, heterosexual transmission is
      increasing and most women are asymptomatic, although the overall mean CD4 count
      is declining over time. There seems to be little evidence of an increased risk of
      pregnancy or delivery complications in HIV-infected pregnancies. Most studies
      have found no increase in adverse pregnancy outcomes, although further research
      is needed. Prospective studies suggest that pregnancy does not promote
      accelerated disease progression in asymptomatic women. Despite earlier concerns,
      three recent studies suggest that pregnancy is not associated with deterioration
      of immunocompetence. The increasing number of infected pregnant women requires
      adequate planning for the future care of their children.

PMID- 9240851
TI  - Epidemiology of HIV/AIDS in women and children in the USA.
AB  - In the USA, the AIDS epidemic has shown dramatic increases among women and
      children in the past decade with more than 70,000 cases in women and 7000 cases
      in children reported. Acquired immunodeficiency syndrome is the seventh leading
      cause of death in children aged 1-4 years and the fourth leading cause of death
      among women aged 25-44 years. Data from the National Survey of Childbearing
      Women, a blinded serosurvey of blood specimens left over from routine metabolic
      screening of most infants born in the USA, indicate that approximately 7000 HIV
      infected women have given birth each year for the past several years. Human
      immunodeficiency virus infection disproportionately affects African-Americans and
      women of Hispanic ethnicity. Most cases in women and children have come from
      states along the east coast and large urban areas. Pneumocystis carinii pneumonia
      (PCP) continues to be the most commonly reported opportunistic infection in
      children with AIDS. As of 31 December, 1995, 2383 cases of PCP had been reported
      to the Centers for Disease Control and Prevention. Revised guidelines for PCP
      prophylaxis published in 1995 will hopefully provide a better means for
      preventing this deadly infection in children with AIDS. In 1994, a clinical trial
      (ACTG 076) found that the risk of perinatal transmission could be reduced by two
      thirds with the use of a zidovudine regimen given antenatally, during labor and
      delivery, and postnatally to the infant. The US Public Health Service published
      guidelines based on these results, recommending voluntary HIV counseling and
      testing for all pregnant women in the USA and zidovudine therapy for those women
      found to be HIV-infected. Since implementation of these guidelines, cases of
      perinatally acquired AIDS in children have begun to decrease. Adequate resources
      for provision of care, outreach to women who do not receive prenatal care,
      training of healthcare personnel and attention to the many social and
      psychological needs of HIV-infected women and their children are key factors for
      further reduction of HIV infection in children.

PMID- 9240852
TI  - Human immunodeficiency virus-1 infection in neonates: correlation of plasma and
      cellular viremia and clinical outcome. French Pediatric Cohort Study Group.
AB  - Among human immunodeficiency virus-1 (HIV-1) vertically infected children, two
      patterns of disease progression have been observed: about 25% develop a severe
      immunodeficiency within the first 2 years of life; the rest experience a slower
      progression, like adults. We have assessed infectious viral burden in infected
      neonates through the French National Prospective Study. Plasma and cell
      associated viremia were assayed by endpoint-dilution cultures in samples from 46
      infants followed prospectively from birth. Plasma and cell-associated viral
      burden were found to be significantly higher in rapid progressing infants than in
      non-progressing infants in the first months of life: before the age of 2 months,
      between 2 and 4 months of age and by the age of 6 months. Moreover, among the non
      progressing children, the infectious viral burden before the age of 4 months was
      predictive of the viral burden measured after the age of 12 months. In
      conclusion, this work demonstrates that infectious viral load is a reliable
      predictive marker for rapid progression to AIDS in infants and could be useful
      for initiating antiretroviral therapy.

PMID- 9240853
TI  - Viral phenotype in mother-to-child HIV-1 transmission and disease progression of
      vertically acquired HIV-1 infection.
AB  - Human immunodeficiency virus-1 (HIV-1) primary isolates differ in replicative
      capacity on peripheral blood mononuclear cells, tropism for primary monocyte
      derived macrophages (MDM) and T-cell lines and syncytium-inducing (SI) capability
      on MT-2 cells in vitro. To assess the role of viral phenotype in mother-to-child
      HIV-1 transmission and the progression of vertically acquired HIV-1 infection, we
      studied 57 HIV-1-infected women at the time of delivery and 24 HIV-1-infected
      infants. Eight mothers transmitted the infection to their children. Primary
      isolates, obtained from 7 and 33 transmitting and non-transmitting mothers,
      respectively, differed in replicative capacity and SI activity, and no
      significant differences between the two groups were found regarding these viral
      properties. However, all primary isolates from transmitting mothers, but about
      half of those from non-transmitting mothers, were able to infect and replicate in
      MDM, regardless of their replicative capacity and/or SI activity; moreover, the
      monocyto-macrophage tropism of the maternal isolate correlated with an increased
      risk of transmission. Viral isolates from HIV-1-infected children were typed
      before 2 months of age; all but four showed a tropism for MDM, further supporting
      the notion that monocyto-macrophage tropic variants are selectively transmitted
      from mother to child and/or selectively replicated upon transmission. Clinical
      follow-up disclosed that 7/11 infants with a rapid/high replicating virus but
      none of the 17 with a slow replicating virus developed severe symptoms of disease
      and/or severe immunodepression by 1 year of age. By means of competitive RNA
      polymerase chain reaction (PCR), a relationship was found between viral phenotype
      and dynamics of HIV-1 replication early in life in children who experienced
      different patterns of disease progression.

PMID- 9240854
TI  - Antiretroviral resistance and HIV vertical transmission.
AB  - The author reviews the current and potential problem of antiviral resistance in
      the prevention of vertical transmission of human immunodeficiency virus (HIV)
      from mother to child. The paper addresses five questions: (i) How often does
      antiretroviral resistance occur? While this does not appear to be an important
      problem now, low levels of resistance are probably common, and resistance can be
      expected to increase in frequency; (ii) Does resistance influence the rate of
      vertical transmission? The answer is likely to be yes if the drug in question is
      used in an effort to prevent or reduce transmission; (iii) What are the
      consequences for the mother? These are certainly not good and might, if the drug
      in question is important for the mother's health, be bad; (iv) What are the
      consequences for the baby? The answer to this question is similar, with the
      additional concern that resistance might make preventive measures less effective
      and thus increase the chance of transmission; (v) What can be done about it?
      Combination treatment may be effective in minimizing the development of
      resistance. As with other antimicrobials, selective and rational use of drugs for
      specific purposes will minimize the problem. The conclusion of the discussion is
      that resistance is likely to emerge as an important problem over time and should
      be addressed in strategies for prevention.

PMID- 9240855
TI  - Role of placental cytokines and inflammation in vertical transmission of HIV
      infection.
AB  - In light of new evidence suggesting that maternal human immunodeficiency virus
      (HIV) infection produces at least a three-fold increase in the number of early
      spontaneous abortions, it is important to search for factors that may predispose
      to fetal wastage. Immunological factors are thought to play an important role in
      permitting the HLA-disparate fetus to continue to term, despite powerful maternal
      immune forces capable of rejection. In the context of a heightened incidence of
      spontaneous abortion in HIV infection, evidence is now accumulating that
      implicates an imbalance in immune factors in contributing to this fetal loss.
      Soluble immune factors, such as cytokines, have been suggested as contributing
      agents to recurrent spontaneous abortions. Inflammatory cytokines-interleukin
      1beta, interleukin 6 and tumor necrosis factor alpha-have been measured in
      isolated placental trophoblastic cells in HIV-infected and non-infected pregnant
      women in an attempt to explore this hypothesis. These inflammatory cytokines and
      their messenger RNAs were significantly elevated before and after stimulation in
      HIV-infected women, supporting the belief that HIV-infected women present their
      fetuses a milieu of imbalanced immune factors capable of contributing to
      immunological rejection. In addition, these elevated inflammatory cytokine levels
      may contribute to HIV disease progression in fetuses by virtue of activation of
      HIV gene transcription factors similar to what has been demonstrated in in vitro
      systems. We therefore propose that HIV infection in pregnant women produces an
      altered state of certain soluble immune factors, which in concert with other
      immune factor abnormalities, such as loss of immune selection in the fetal
      thymus, predisposes the fetus to advanced HIV infection and possible spontaneous
      abortion.

PMID- 9240856
TI  - Role of immunity in maternal-infant HIV-1 transmission.
AB  - Factors influencing human immunodeficiency virus type 1 (HIV-1) mother-to-child
      transmission include both immunological and virological parameters: higher viral
      loads have been associated with clinical stage of HIV-1-infected individuals as
      well as higher risk of mother-to-child transmission. Furthermore, we have shown
      that transmitting mothers more frequently harbour HIV-1 isolates with rapid/high
      syncytium-inducing (SI) biological phenotype than non-transmitting mothers do.
      Genetically homogeneous virus populations have been found in HIV-1-infected
      children at birth, in contrast to the heterogeneous virus populations often found
      in their infected mothers. This observation suggests that a few virus variants
      are transmitted or initially are replicating in the child. By comparing the HIV-1
      gp120 V3 region of sequentially obtained samples from infected children with
      samples obtained from their mothers at delivery we found, however, that multiple
      variants of HIV-1 with different outgrowth kinetics can be transmitted. In
      addition, we have obtained results indicating an impaired ability of the immune
      response to adapt to the sequence evolution of HIV-1 in transmitting mothers, as
      assessed by measuring serum reactivities to peptides representing selected yet
      closely related V3 sequences. By analysing the presence of antibodies in maternal
      serum at delivery, which neutralize autologous isolates as well as other primary
      virus isolates, we have indications that a protective immunity in HIV-1 mother-to
      child transmission might exist. Immunotherapy has been assessed in infected adult
      individuals by passive immunization with a variety of HIV-1-specific antibody
      products. Data from these studies indicated a differential response to therapy
      according to the stage of the disease. Active vaccine strategies, including
      envelope glycoproteins, pursued so far in seronegative adult subjects have shown
      limitations because broadly neutralizing antibodies, such as can be found in
      infected individuals, have not been evoked. Further investigations are therefore
      needed to give support for the potential use of either passive and/or active
      immunization for the prevention of HIV-1 mother-to-child transmission.

PMID- 9240857
TI  - Immunological and virological markers of disease progression in HIV-infected
      children.
AB  - Polymerase chain reaction (PCR), virus culture and antigen detection assays are
      useful for early detection of vertically transmitted human immunodeficiency virus
      type 1 (HIV-1) infection in infants under 12 months of age. Sixty-four children
      born to HIV-1-seropositive mothers were evaluated. Thirteen children (20.3%) were
      repeatedly positive by PCR analysis. There was 100% concordance between the
      results obtained from PCR and culture assays. Measurement of p24 antigen in serum
      was, in contrast, a less sensitive marker of HIV infection: only 5/13 infants had
      positive p24 antigen results. We have investigated the relationship among the HIV
      1 biological phenotype, replicative capacity of viral isolates, HIV RNA copy
      number in plasma, p24 antigenaemia, CD4 T lymphocyte counts and the clinical
      status in 13 HIV-infected infants. Six out of 13 HIV-1 isolates from these
      patients were classified as rapid/high and seven as slow/low. We have found a
      significantly positive correlation between the replication rate of HIV isolates
      and their capacity to induce syncytia in vitro. The HIV-1 isolates with
      rapid/high and syncytium-inducing phenotype, and isolates with slow/low and non
      syncytium-inducing phenotype were obtained from infants who had HIV-1 RNA copy
      number ml(-1) plasma values of 27654-83520 and 1342-34321, respectively. Levels
      of HIV-1 RNA were measured in sequential plasma samples from three HIV-infected
      infants and their biological properties determined in vitro. Our findings
      indicate that infants who carried viruses with more cytophatic biological
      phenotype and who had higher viral RNA copy numbers in blood were more likely to
      have lower CD4+ T cell counts and more likely to develop full-blown AIDS.

PMID- 9240858
TI  - Maternal clinical factors influencing HIV-1 transmission.
AB  - The complex puzzle of maternal factors involved in mother-to-child human
      immunodeficiency virus type 1 (HIV-1) transmission is being put together. The
      risk of perinatal infection increases with mother's disease progression, but it
      remains stable in women seroconverting to HIV-1 during pregnancy and in
      consecutive pregnancies. Thus, transmission correlates with the HIV-1 progression
      rather than the duration of infection in the mother. Nutritional alterations such
      as vitamin A deficiency may also have a significant impact, whereas geographic
      origin and mode of maternal infection are of no influence. Placenta membrane
      inflammation and concurrent sexually transmitted diseases are other significant
      covariates. The rate of transmission appears directly correlated with maternal
      age and inversely with length of gestation. A protective effect of caesarean
      section has been reported in some observational studies but, being controversial,
      these results need to be corroborated by randomized trials.

PMID- 9240859
TI  - Vertical transmission of human immunodeficiency virus type 1: insights from
      studies of multiple pregnancies.
AB  - Because twins share an in utero environment and genetic relationships,
      similarities and differences between them can provide insight into the
      epidemiology and natural history of infectious agents, especially human
      immunodeficiency virus type 1 (HIV-1). Three projects were summarized: HIV-1
      transmission and AIDS-free survival in The International Registry of HIV-Exposed
      Twins; cloning and sequencing of HIV-1 proviral sequences in two sets of
      identical twins; and transmission and natural history of ovine lentivirus (OvLV)
      in twin lambs. Both HIV-1 and OvLV transmission were increased for first-born
      twins. With HIV-1, progression to AIDS appeared independent of zygosity.
      Development of pneumonitis with experimental OvLV infection was highly concordant
      in monozygotic lambs. Finally, the identical infected twins in one set had
      intermingling of each infant's HIV-1 quasispecies, whereas in the second set each
      twin had its own distinct cluster of quasispecies around a maternal sequence. The
      studies indicate that most transmission occurs during labor or delivery, and they
      suggest that immunogenetics may not affect susceptibility to different HIV-1
      quasispecies but may affect the manifestations of specific opportunistic
      diseases.

PMID- 9240860
TI  - Early spontaneous abortions and fetal thymic abnormalities in maternal-to-fetal
      HIV infection.
AB  - The thymus is thought to play a major role in the immunopathogenesis of human
      immunodeficiency virus (HIV) infection, particularly in maternal-to-fetal HIV
      transmission. Characteristic lesions of the HIV-infected thymus include a
      prominent CD4+ CD8+ T lymphocyte depletion at the corticomedullary junction, the
      region of the thymus where immune selection occurs. At least threefold excess
      early spontaneous abortions were noted in a cohort of 124 HIV-infected pregnant
      women. In these 13 abortuses a very high rate (54%) of HIV vertical transmission
      was documented, with the thymus gland particularly affected. It is possible that
      the thymic insult in HIV-infected fetuses contributes to immune rejection of the
      fetus, possibly by an imbalance of maternal and fetal T1- and T2-type cytokines,
      known to be important in HIV disease progression. We propose, therefore, that the
      early spontaneous abortions occurring in HIV-infected pregnant women are due, at
      least in part, to abnormal immune forces created by HIV infection of the thymus.

PMID- 9240861
TI  - Identification of HIV infection in pregnancy: another era.
AB  - In order to be successfully implemented, some interventions to prevent vertical
      transmission of human immunodeficiency virus (HIV) will require prior
      identification of HIV-infected women. The testing and counselling of pregnant
      women should therefore be promoted. Promoting testing and counselling within
      prenatal clinics would be a good strategy; however, additional data on the social
      and economic implications of HIV testing are needed to demonstrate the relevance
      of such a strategy. Promotion of testing and counselling should be developed in
      collaboration with community-based organizations, non-governmental organizations
      and people living with HIV, in order to increase the involvement and
      understanding of the community at large.

PMID- 9240862
TI  - Anonymous testing of newborn infants for HIV antibodies as a basis for estimating
      prevalence of HIV in childbearing women: the 1991-1994 study in Spain.
AB  - During 1991-1994, anonymous screening of newborn infants for maternal antibody to
      human immunodeficiency virus (HIV) was carried out in three regions of Spain:
      Valencia, Galicia and Sevilla. The newborn infants whose heel-stick blood eluates
      were satisfactory for HIV antibody tests were a consecutive series of 104 876,
      representing 99.3% of all newborn infants undergoing routine metabolic screening
      and estimated as comprising at least 98% of all births in the three regions.
      Enzyme immunoassay (EIA) positives were confirmed by immunoblot, yielding 246
      confirmations: a rate of 2.3 per 1000. Seropositivity rates ranged from 1.4 per
      1000 in Galicia to 2.1 in Sevilla and 3.1 in Valencia, and remained relatively
      stable in each region during the years of the study. Within socioeconomically
      defined subgroups of birth hospitals in Valencia and Galicia, all subgroups
      contained seropositives, even though there was a twofold to fivefold over
      representation in the "inner city" public hospitals. To estimate the proportion
      of HIV-1-seropositive newborn infants who were positive for HIV-1 DNA, polymerase
      chain reaction (PCR) assays were performed on 165 dried blood spots that had been
      retained following positive immunoblot assays. Fifteen (9%) were PCR positive,
      and when this proportion is adjusted for the age-specific sensitivity of the
      method, it translates into an estimated HIV-1 transmission rate of 24% (range 18
      36%). For 94,906 of the 104,876 newborn infants screened, the EIA used could
      detect antibodies that react with epitopes of HIV-1 and HIV-2. There were 30
      newborn infants whose blood eluate was positive by this combined HIV-1/HIV-2
      antibody screen and whose secondary screening with monovalent HIV-2 and HIV-1 EIA
      indicated that the HIV-2 reactivity was above the cut-off whereas the HIV-1 was
      not. Ranking these 30 results according to absolute HIV-2 reactivity and relative
      reactivity with respect to HIV-1 indicated that four infants were probable true
      HIV-2 seropositives and a total of 12 were possible HIV-2 seropositives, a
      prevalence of the order of 1:10000 to 1:20000 newborn infants. These anonymous
      population-based serological studies provide "leading-indicator" data to
      complement traditional AIDS surveillance for epidemiological and planning
      purposes.

PMID- 9240863
TI  - The future of prenatal HIV testing.
AB  - The use of zidovudine for the prevention of mother-to-child transmission of human
      immunodeficiency virus, as well as continuing advances in our understanding of
      the determinants of that transmission, and of potential new avenues of
      intervention augur ever more efficient perinatal prevention strategies in the
      near future. In this paper the evolving role of prenatal testing in an era of
      ever more successful interventions will be discussed. At least four factors will
      be critical in determining what that role will be: clinical, legal, ethical and
      economic. Each of these are parochial, i.e. they will feature in eradication
      strategies in different ways in different geographical, economic and cultural
      settings. An understanding of these factors will help to suggest what course
      testing policy should take and to determine the role clinicians must play if any
      testing policy is to succeed in contributing to the end of pediatric HIV disease.

PMID- 9240864
TI  - Human immunodeficiency virus type 1 infection, clinical trials and ethics in
      paediatrics.
AB  - Children are not little adults and questions regarding their treatment must be
      directly addressed to children. Phase I and II trials should closely follow those
      in adults, integrated by separate studies in infants. Phase III trials should be
      carried out in a parallel fashion, flexible enough to be modifiable according to
      results from larger studies in adults. On condition that study designs are
      ethically impeccable and are respectful of the intrinsic social weakness of
      children, as many children as possible should enter clinical trials to offer wide
      access to drugs and ensure that questions are addressed as rapidly and
      efficiently as possible.

PMID- 9240865
TI  - Birth outcomes following zidovudine exposure in pregnant women: the
      Antiretroviral Pregnancy Registry.
AB  - Potential risk of adverse birth outcomes associated with the use of
      antiretrovirals in human immunodeficiency virus (HIV)-infected women during
      pregnancy must be assessed. Data through June 1995 are reported from the
      worldwide Antiretroviral Pregnancy Registry on the incidence of structural birth
      defects following prenatal exposure to zidovudine. Healthcare professionals
      register pregnant women anonymously. Follow-up is at time of delivery. Results
      are reviewed semi-annually by an advisory committee, which follows the Centers
      for Disease Control and Prevention (CDC) guidelines for definitions of birth
      defects. From 1989 through to 30 June, 1995, 198 outcomes involving exposure to
      zidovudine were reported. Of 73 first-trimester exposures, outcomes included one
      infant with a birth defect. Of 125 exposures in the second and third trimesters,
      six infants were reported with birth defects. Data on other antiretrovirals are
      insufficient for analysis. The Registry findings to date do not show an increase
      in the number of birth defects (1/63 in the first trimester, or 1.59%, 95% CI
      0.083%, 9.69%) following prenatal zidovudine exposure when compared with that
      expected in the general population; however, the number of outcomes to date
      represents a sample of insufficient size for developing precise estimates
      regarding the teratogenic risk of zidovudine.

PMID- 9240867
TI  - Progress in prevention of perinatal HIV-1.
AB  - The findings of a recent human immunodeficiency (HIV-1) prevention trial in the
      USA demonstrated that administration of an antiretroviral drug, zidovudine, to
      mothers during the prenatal and intrapartum periods, and to their neonates for 6
      weeks, resulted in a two-thirds reduction in risk of perinatal transmission from
      25.5% to 8.3%. These results were rapidly disseminated both in the USA and
      internationally. Since the release of these clinical trial results in the spring
      of 1994, several observational studies have documented a sharp increase in
      maternal and neonatal zidovudine use, as well as a significant decrease in
      perinatal HIV-1 transmission, with rates of about 8% being observed in non
      clinical trial settings. Internationally, the results have led to the development
      of a variety of perinatal prevention trials that build on the success of the U.S.
      perinatal prevention trial but use modified strategies that can feasibly be
      carried out in developing countries.

PMID- 9240866
TI  - Reducing the risk of perinatal HIV-1 transmission with zidovudine: results and
      implications of AIDS Clinical Trials Group protocol 076.
AB  - This paper reviews the rationale for the AIDS Clinical Trials Group (ACTG)
      protocol 076 design, the study results and the implications of these results,
      including discussion of the US Public Health Service Task Force recommendations
      on the use of zidovudine to reduce perinatal transmission and for prenatal human
      immunodeficiency virus (HIV) counseling and testing.

PMID- 9240868
TI  - Human immunodeficiency virus infection and mode of delivery.
AB  - Most children acquire human immunodeficiency virus (HIV) infection vertically
      from an infected mother. Indirect evidence suggests that a substantial proportion
      of infection is acquired around the time of delivery, which suggests that this
      would be an appropriate time to intervene. If intrapartum transmission of HIV
      occurs primarily through direct exposure of the infant to cell-associated or free
      HIV in genital secretions or blood during passage through the birth canal, or by
      ascending infection, caesarean section performed prior to labour might reduce the
      risk of transmission. There is insufficient evidence to justify routine caesarean
      section deliveries for HIV-infected women, and a randomized clinical trial of
      mode of delivery has started in Europe.

PMID- 9240869
TI  - Overview of the potential role of vitamin A in mother-to-child transmission of
      HIV-1.
AB  - Vitamin A is an essential micronutrient for normal immune function. Vitamin A
      deficiency is common among human immunodeficiency virus (HIV)-infected pregnant
      women and is associated with higher mother-to-child transmission of HIV-1 and
      increased infant mortality. The biological mechanisms by which vitamin A
      deficiency could influence mother-to-child transmission of HIV-1 include
      impairment of immune responses in both mother and infant, abnormal placental and
      vaginal pathology and increased HIV viral burden in breastmilk and blood.
      Clinical trials are currently in progress to determine whether daily
      micronutrient supplementation, including vitamin A, during pregnancy can reduce
      mother-to-child transmission of HIV-1.

PMID- 9240870
TI  - Breastfeeding and vertical transmission of HIV-1.
AB  - An estimated one-third to one-half of vertical transmission of human
      immunodeficiency virus type 1 (HIV-1) worldwide is due to breastfeeding. The
      exact frequency of breast milk HIV-1 transmission is unknown, but it has been
      estimated to be 14% in the setting of established maternal HIV-1 infection and
      29% in the setting of acute maternal infection. The timing of breast milk
      transmission during the course of lactation also remains unknown, but two studies
      have found an association between duration of breastfeeding and risk of infant
      infection. In one such study, prolonged breastfeeding for 15 months or longer was
      associated with a twofold increased transmission risk. Human immunodeficiency
      virus type 1 DNA can be detected in over 50% of breast milk samples and is
      correlated with CD4 depletion and vitamin A deficiency. The presence of breast
      milk HIV-1 provirus is associated with increased transmission risk. Many current
      intervention strategies to prevent vertical transmission of HIV-1 are aimed at in
      utero or perinatal transmission. In developing countries in which breastfeeding
      by HIV-1 infected women is recommended practice, additional intervention
      strategies to reduce breast milk transmission warrant evaluation.

PMID- 9240871
TI  - Medical care and SIDS.

PMID- 9240872
TI  - Plasma and serum micronutrient concentrations in preschool children.
AB  - The plasma concentrations of vitamin A, vitamin E, beta-carotene and serum
      concentrations of zinc, retinol-binding protein and prealbumin were examined for
      a random cluster sample, stratified by socioeconomic status, of 467 healthy
      preschool children. Children were aged 9-62 months; 44% were females. The mean
      plasma values were: vitamin A, 1.29 micromol l(-1); vitamin E, 18.9 micromol l(
      1); and beta-carotene, 0.30 micromol l(-1). The mean serum values were: zinc,
      13.9 micromol l(-1); retinol-binding protein, 25.5 mg l(-1); and prealbumin,
      186.2 mg l(-1). The mean molar ratio of vitamin A to retinol-binding protein for
      the study group was 1.10. There were no differences in the mean values of any of
      the measured micronutrients between the genders. The results of this survey do
      not indicate that the prevalence of micronutrient deficiency in this preschool
      population is of public health significance.

PMID- 9240873
TI  - Follow-on formula in the prevention of iron deficiency: a multicentre study.
AB  - Six-month-old infants were recruited at 21 centres in the UK and Ireland and
      randomly assigned to receive matching iron-fortified (12.3 mg/l iron) or non
      fortified (1.4 mg/l iron) formula for 9 months. Infants already receiving cow's
      milk continued this feed. Haematological indices and iron status were evaluated
      at age 6 months, 9-10 months and 15 months. Four hundred and six infants entered
      and 302 completed the study. There were no differences between the groups for
      increases in weight, head circumference or length. Significant differences
      between the groups were observed at 15 months for haemoglobin, serum ferritin,
      serum iron and total iron binding capacity. Haemoglobin levels were < 110 g/l in
      33% of infants fed cow's milk compared with 13% and 11% in those receiving non
      iron-fortified and iron-fortified formula respectively. The corresponding figures
      for serum ferritin < 10 microg/l were 43%, 22% and 6%. Follow-on formula provides
      an acceptable vehicle for preventing iron deficiency in this vulnerable group.

PMID- 9240874
TI  - Effects of malnutrition on the erythrocyte fatty acid composition and plasma
      vitamin E levels of Pakistani children.
AB  - Erythrocyte fatty acids and plasma vitamin E concentrations were determined in 47
      grade 2 and 21 grade 3 malnourished Pakistani children (ages 4-56 months). Data
      were compared with those of 26 age- and sex-matched apparently healthy controls.
      Evaluation with three statistical approaches revealed that both grade 2 and grade
      3 malnourished children had decreased erythrocyte omega6 fatty acids and to a
      lesser extent decreased omega3 fatty acids. These decreases were compensated for
      by increased omega9 fatty acids. The patients tended to have lower plasma vitamin
      E concentrations. We conclude that malnourished Pakistani children have low
      essential fatty acid status, notably those of the omega6 series. The combination
      of low erythrocyte 22:6omega3 and a low 22:5omega6/22:4omega6 ratio in grade 2
      patients suggests low delta4-desaturation activity, which may be due to impaired
      peroxisomal beta-oxidation.

PMID- 9240875
TI  - Platelet serotonin transporter in coeliac disease.
AB  - We investigated a peripheral serotonergic marker, i.e. platelet tritiated
      imipramine (3H-IMI) binding sites, which are part of the 5-HT transporter complex
      similar to that present in the brain, in 20 patients affected by coeliac disease
      (CD), as compared with 20 healthy controls. Platelet membranes and 3H-IMI binding
      were carried out according to a standardized protocol. The results showed that
      coeliac patients had significantly lower 3H-IMI binding sites than controls. This
      finding would suggest the presence of a dysfunction at the level of the 5-HT
      transporter that might underline the psychic disturbances frequently observed in
      coeliac patients.

PMID- 9240876
TI  - High risk of Helicobacter pylori infection associated with cow's milk antibodies
      in young diabetics.
AB  - Antibody titres (IgA and IgG) for Helicobacter pylori were assayed in 69 insulin
      dependent diabetes mellitus patients (42 males, age 1-20 years) and 310 healthy
      controls (171 males, age 1-20 years). A positive antibody titre for Helicobacter
      pylori was found in 18/69 diabetic subjects compared to 17/310 controls (p <
      0.001). There was no difference between Helicobacter pylori positive and negative
      diabetic subjects as regards age, sex, duration of diabetes, diabetic control,
      insulin dose and SDS for weight and height. Gastroduodenoscopy revealed presence
      of Helicobacter pylori and evidence of gastric inflammation in 7/8 symptomatic
      diabetic children. There was a significant association in the diabetic subjects
      between positivity for anti-cow's milk protein and anti-Helicobacter antibodies,
      compared to the control group. Seven of the 17 diabetics studied within 3 months
      of the onset of diabetes had positive antibody titres for Helicobacter. Of these
      seven patients, five were positive for anti-cow's milk protein antibodies. In our
      study the prevalence of Helicobacter pylori infection was significantly higher in
      diabetic subjects than in controls, but the infection was asymptomatic and there
      was no correlation with diabetes control. In diabetic subjects Helicobacter
      pylori infection was associated with a humoral response to cow's milk proteins
      and was often present from the onset of diabetes.

PMID- 9240877
TI  - Bone mineral density and metabolism in children with congenital hypothyroidism
      after prolonged L-thyroxine therapy.
AB  - The effect of long-term L-thyroxine (LT4) replacement therapy on bone mineral
      density and on biochemical markers of bone turnover were studied in children with
      congenital hypothyroidism (CH). Forty-four children and adolescents (mean age 8.5
      +/- 3.5 years) with primary CH who began LT4 replacement therapy within the first
      month of life were studied. Bone mineral density (BMD) of the lumbar vertebrae
      and the upper femoral bone was measured by dual energy X-ray absorptiometry.
      Serum osteocalcin (OC) and bone alkaline phosphatase were measured as markers of
      bone formation and urinary deoxypyridinoline was taken as a marker of bone
      resorption. Bone mineral densities of CH children were not different from those
      in age-matched controls. The biochemical markers of bone turnover were normal
      except for the serum OC levels which were found to be higher than in controls and
      positively correlated with the free thyroid hormone levels (for FT4 r = 0.42, p =
      0.02). Eight CH children demonstrated low BMD values (below -1 SDS) at -2 +/- 0.7
      SDS for the lumbar spine and -1.6 +/- 0.5 SDS for the femoral site. These eight
      children showed lower mean weight (p < 0.05) and their dietary calcium intake
      tended to be less (p <0.06) than that seen in the normal BMD group. In
      conclusion, our results show that LT4 replacement therapy for 8 years is not
      detrimental to the skeletal mineralization of CH children. As in a healthy
      population, weight and current intake of calcium seem to be major determinants of
      bone density. Dietary recommendations, especially when calcium intake is below
      the recommended dietary allowance, may have to be reconsidered.

PMID- 9240878
TI  - Parental mosaicism and autosomal dominant mutations causing structural
      abnormalities of collagen I are frequent in families with osteogenesis imperfecta
      type III/IV.
AB  - Protein-chemical and molecular studies were conducted on all osteogenesis
      imperfecta (OI) type III/IV patients referred to our hospital during the last 15
      y. Of a total of 16 OI type III/IV patients studied, 15 patients were
      heterozygous for a mutation in one of the two genes coding for collagen I, COL1A1
      or COL1A2. Cultured fibroblasts from these 15 patients produced both normal and
      abnormal collagen I molecules, pointing to a dominant-negative effect of the
      mutation. Nine mutations had not been described previously. Parental mosaicism
      was demonstrated in three families. In the 16th child the causative mutation was
      not found. In conclusion, OI type III/IV in most patients of Western European
      ancestry is caused by dominant mutations in the genes for collagen I, and
      recurrence of OI is caused in most cases by parental gonadal mosaicism.

PMID- 9240879
TI  - Circadian blood pressure changes in untreated children with kidney disease and
      conserved renal function.
AB  - Ambulatory blood pressure monitoring over 24 h was applied in 31 children with
      kidney disease, aged 3-19 (median 11) years, in the absence of renal
      insufficiency and without antihypertensive therapy. Median creatinine clearance
      was 112 ml/min/1.73m2. Ambulatory blood pressure monitoring revealed that eight
      patients (26%) were hypertensive during the daytime, compared to 62% through
      casual recordings obtained in the office and 38% when blood pressure was taken at
      home. Nocturnal hypertension was detected by ambulatory monitoring in six
      patients, two of whom had normal blood pressure in the daytime. Median nocturnal
      dipping was 13% for systolic and 21% for diastolic blood pressure, i.e. similar
      to healthy children. Rhythm analysis recognized a distorted circadian pattern for
      systolic and/or diastolic blood pressure in eight patients. In conclusion,
      ambulatory blood pressure monitoring allows the evaluation of hypertension more
      reliably than casual recordings in the office. Nocturnal hypertension, as a major
      risk factor for renal deterioration, is detected in a similar proportion as
      daytime hypertension in almost 20% of untreated children with kidney disease and
      normal renal function.

PMID- 9240880
TI  - Improving outcome of malignant brain tumours in very young children: a population
      based study in Finland during 1975-93.
AB  - Sixty-four children with malignant brain tumours diagnosed at less than 3 years
      of age were reported to the Finnish Cancer Registry from 1975 to 1993. The
      survival rate has improved significantly: the 5-year survival rate was 26% for
      all children, 13% for children diagnosed during 1975-85 (n = 30) and 40% for
      those diagnosed during 1986-93 (n = 34). Of the surviving children in 1986-93,
      43% were categorized in Bloom's group I or II and could lead active lives without
      major disabilities. The remaining children had severe neurologic late
      complications, such as hemiplegia, intractable seizures, and mental retardation.

PMID- 9240881
TI  - Epidemiology of traumatic brain injury in children and adolescents in south
      western Sweden.
AB  - The objectives of this study were to outline the incidence, gender distribution,
      external causes, severity and early outcome of traumatic brain injury (TBI). The
      subjects were children and adolescents in the south-western Swedish health care
      region, aged 0-17 y in 1987-1991 and fulfilling the criteria for TBI.
      Identification was made from the discharge registers of the hospitals in the
      region admitting patients with TBI, and outcome data were obtained from medical
      records. The mean incidence rate was 12/100,000 for TBI. The dominant external
      cause was traffic (60%), followed by falls (22%). At discharge, 49% of those
      surviving were healthy, 48% suffered from one functional impairment and 52%
      suffered from two or more impairments. In conclusion, although the incidence rate
      of TBI is low in Sweden, the condition causes permanent functional impairment in
      6/100,000 cases every year.

PMID- 9240882
TI  - The contribution of developmental surveillance to early detection of cerebral
      palsy.
AB  - A retrospective study of the contribution of examinations at Child Health Centres
      (CHC) for early detection of cerebral palsy (CP) was performed in 23,924
      children, born in 1986-90, in the south-western part of Stockholm County. The
      outcome assessed was age of referral to a habilitation unit. A total of 66
      children with CP (2.76/1000) were identified through the register at the
      responsible habilitation unit. The age of referral was, median 8 months, mean
      12.4 months and range 0.5-54 months. A peak of referrals at 8-9 months was
      produced by CHC checks at 6 months of age. No other examination at the CHC
      resulted in a significant number of referrals. Nineteen records from CHC
      concerning moderate and severe cases were reviewed. Out of all examinations with
      aberrant findings only 11/20 resulted in referrals or further examinations. No
      child with moderate or severe CP was referred due to developmental screening test
      findings only.

PMID- 9240883
TI  - Psychosocial factors in children with idiopathic musculoskeletal pain: a
      prospective, longitudinal study.
AB  - To explore the role of psychosocial factors in the development and persistence of
      idiopathic musculoskeletal pain (IMP) in children, 23 children with IMP and 52
      children with juvenile chronic arthritis (JCA) were compared at first admission
      to hospital and at 9 y follow-up. Semistructured interviews were performed at
      both assessments. At first admission, the prevalence of psychiatric diagnoses was
      high both in patients with IMP and patients with JCA, but patients with IMP more
      often had pain models, reported more school stress and more often lived with one
      biological parent. At follow-up, overall psychosocial functioning and level of
      chronic family difficulties were improved in both groups, but patients with IMP
      had a higher prevalence of psychiatric diagnoses and more chronic family
      difficulties and life events than patients with JCA. The persistence of IMP at
      follow-up was related to pain models, school stress, less parental education and
      more chronic family difficulties at first admission. Findings support the
      association between psychosocial factors and childhood IMP.

PMID- 9240884
TI  - A simplified surfactant dosing procedure in respiratory distress syndrome: the
      "side-hole" randomized study. Spanish Surfactant Collaborative Group.
AB  - The aim of this study was to compare the incidence of acute adverse events and
      long-term outcome of two different surfactant dosing procedures in respiratory
      distress syndrome (RDS). The effects of two surfactant dosing procedures on the
      incidence of transient hypoxia and bradycardia, gas exchange, ventilatory
      requirements and 28 d outcome were compared. The patients, comprising 102 infants
      (birthweight 600-2000 g) with RDS on mechanical ventilation with FiO2 > or = 0.4,
      were randomized at 2-24 h to receive 200 mg kg(-1) of Curosurf; in 56 it was
      given by bolus delivery, and in 55 by a simplified technique (dose given in 1 min
      via a catheter introduced through a side-hole in the tracheal tube adaptor. The
      baby's position was not changed and ventilation was not interrupted). Two
      additional surfactant doses (100 mg kg(-1)) were also given, by the same method,
      if ventilation with FiO2 > or = 0.3 was needed 12 and 24 h after the initial
      dose. The number of episodes of hypoxia and/or bradycardia was similar in both
      groups. A slight and transient increase in PaCO2 was observed in the side-hole
      group. The efficacy of the surfactant, based on oxygenation improvement,
      ventilator requirements, number of doses required and incidence of air leaks, was
      similar. No differences were observed in the incidence of intraventricular
      haemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia or survival. In
      conclusion, a simplified surfactant dosing procedure not requiring fractional
      doses, ventilator disconnection, changes in the baby's position or manual bagging
      was found to be as effective as bolus delivery. The number of dosing-related
      transient episodes of hypoxia and bradycardia was not decreased by the slow, 1
      min, side-hole instillation procedure.

PMID- 9240885
TI  - Clinical and echocardiographic evaluation of neonates with heart murmurs.
AB  - In this study, 116 neonates (58M, 58F), aged 12h to 14d, with heart murmurs were
      examined by echocardiography: 26 were preterm and 90 full-term neonates. The
      clinical diagnosis was classified into definite heart disease, possible heart
      disease and innocent murmur. The final diagnosis was based on echocardiography
      and, in some cases, cardiac catheterization or surgery. The results showed that
      97 (84%) neonates had heart diseases; 19 (16%) had a normal heart, including 7
      with tricuspid regurgitation and 9 with physiological peripheral pulmonic
      stenosis. Out of 88 neonates with clinically definite heart disease, the final
      diagnosis was changed to normal heart in 9 (10%) cases and the lesion-specific
      diagnosis was changed in 9 (10%) neonates. In four cases, the clinical diagnosis
      of ventricular septal defect or pulmonary stenosis was changed to double-outlet
      right ventricle, single ventricle, hypoplastic left heart syndrome or tetralogy
      of Fallot. The clinical diagnosis was correct in 77-85% for varying simple
      lesions. In 5 of 21 neonates with clinically possible heart disease, the
      diagnosis was changed to normal heart. In one of six neonates with clinically
      innocent murmurs, the diagnosis was changed to small muscular ventricular septal
      defect. We concluded that 84% of heart murmurs in neonates were due to heart
      diseases and only 16% were innocent murmurs. Although clinical evaluation could
      determine the presence or absence of heart disease in most neonates, the lesion
      specific diagnosis was not quite satisfactory. Echocardiography is necessary for
      neonates with a clinically diagnosed heart disease or possible heart diseases,
      and may be unnecessary for those with innocent murmurs diagnosed by
      paediatricians.

PMID- 9240886
TI  - The value of a scoring system for hypoxic ischaemic encephalopathy in predicting
      neurodevelopmental outcome.
AB  - A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy
      during the neonatal period was tested. The value of the score in predicting
      neurodevelopmental outcome at 1 y of age was assessed. Forty-five infants who
      developed hypoxic ischaemic encephalopathy after birth were studied
      prospectively. In addition to the hypoxic ischaemic encephalopathy score all but
      two infants had at least one cranial ultrasound examination. Thirty-five infants
      were evaluated at 12 months of age by full neurological examination and the
      Griffiths Scales of Mental Development. Five infants were assessed at an earlier
      stage, four who died before 6 months of age and one infant who was hospitalized
      at the time of the 12 month assessment. Twenty-three (58%) of the infants were
      normal and 17 (42%) were abnormal, 16 with cerebral palsy and one with
      developmental delay. The hypoxic ischaemic encephalopathy score was highly
      predictive for outcome. The best correlation with outcome was the peak score; a
      peak score of 15 or higher had a positive predictive value of 92% and a negative
      predictive value of 82% for abnormal outcome, with a sensitivity and specificity
      of 71% and 96%, respectively. For the clinician working in areas where
      sophisticated technology is unavailable this scoring system will be useful for
      assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of
      neurodevelopmental outcome.

PMID- 9240887
TI  - Gut hormone concentrations in preterm infants with necrotizing enterocolitis.
AB  - Blood levels of gastrin, neurotensin and vasoactive peptide (VIP) were estimated
      in 14 premature infants with necrotizing enterocolitis (NEC) and in 12 controls.
      In comparison to the control group, infants with NEC had (a) significantly lower
      gastrin levels both before [9.3 (7.8) versus 33.7 (27.1)] and after [52.4 (48.1)
      versus 100.8 (50.9)] the development of NEC; (b) significantly lower neurotensin
      levels only after the development of NEC [37.8 (10.4) versus 54.5 (20.6)1; and
      (c) no significant difference in VIP values [25.4 (9.7) versus 18.9 (9.9) and
      24.5 (15.7) versus 26.1 (19.1)]. It is concluded that NEC can adversely affect
      gastrin and neurotensin concentrations in the blood.

PMID- 9240888
TI  - 5-Hydroxy-3-indole acetic acid levels in infantile colic: is serotoninergic tonus
      responsible for this problem?
AB  - Levels of 5-hydroxy-3-indole acetic acid (5-OH IAA), a metabolite of serotonin,
      were studied in infants with infantile colic in order to investigate the
      aetiology of infantile colic pathogenesis. The study included 16 patients with
      infantile colic and 10 control subjects. Random urinary 5-OH IAA levels of
      colicky infants were found to be higher than those in the control group. This
      finding suggested that high serotonin levels may be responsible for infantile
      colic.

PMID- 9240889
TI  - Respiratory syncytial virus pneumonia ventilated with high-frequency oscillatory
      ventilation.
AB  - Four infants below 6 months of age with proven respiratory syncytial virus
      infection in need of assisted mechanical ventilation were successfully treated by
      high-frequency oscillatory ventilation. One of the four infants fulfilled the
      criteria for extracorporeal membrane oxygenation before the start of oscillation,
      and one on the second day on high-frequency oscillatory ventilation. However,
      extracorporeal membrane oxygenation was not needed in any of the infants. All
      survived, and three appeared to be without any pulmonary sequelae.

PMID- 9240890
TI  - Neonatal pleural empyema with group A Streptococcus.
AB  - A case of early neonatal septicaemia with pneumonia and pleural empyema is
      reported. The causal microorganism was beta-haemolytic Streptococcus pyogenes
      group A originating from the mother, who had a perineal infection and
      bacteraemia.

PMID- 9240891
TI  - Improved triglyceride control with low glycaemic index-high carbohydrate modified
      lipid diet in a hypertriglyceridaemic child.
AB  - This study reports a 7-y-old boy with severe hypertriglyceridaemia who was
      successfully treated for 6 y with a low glycaemic index-high carbohydrate
      modified-lipid diet that produced beneficial changes in triglyceride and total
      cholesterol levels. It is suggested that a selection of a complex digestible
      carbohydrate and an adequate ratio between polyunsaturated and monounsaturated
      fat may, in the long term, favourably improve the lipid profile.

PMID- 9240892
TI  - Effects of a low selenium state in patients with phenylketonuria.
AB  - Eighty-seven participants of the German Collaboratory Study for Children with
      Phenylketonuria (PKU) presented low plasma, whole blood and hair selenium (Se)
      values, reduced urinary selenium excretion, and decreased plasma and erythrocyte
      glutathione peroxidase activity in comparison with a healthy reference group (all
      figures p < 0.001). Aspartate amino transferase and thyroxine (T4) concentrations
      in plasma were inversely correlated with the selenium blood values of the PKU
      children. Somatic measurements showed a negative standard deviation score of body
      height in the PKU children compared with reference values. Despite the different
      Se supply, the infants did not present any specific Se deficiency symptoms.

PMID- 9240894
TI  - Pulmonary artery pressure in term and preterm neonates revisited.

PMID- 9240893
TI  - Malignant B-cell lymphoma in an infant with severe combined immunodeficiency with
      short-limbed skeletal dysplasia.
AB  - In an infant with skeletal anomalies and haemolytic disease, intestinal
      perforation was caused by necrosis of an as yet undetected B-cell lymphoma.
      Severe combined immunodeficiency with short-limbed skeletal dysplasia was
      diagnosed. This is the first published report of a patient with this syndrome in
      combination with haemolytic disease and B-cell-lymphoma.

PMID- 9240895
TI  - Maternal and fetal hemoglobin (Hb) levels and their iron status.

PMID- 9240896
TI  - Autoimmunity and congenital permanent diabetes mellitus: a response.

PMID- 9240897
TI  - Lactobacillus GG supplementation does not reduce faecal colonization of
      Klebsiella oxytoca in preterm infants.

PMID- 9240898
TI  - Posttransplant lymphoproliferative disease of donor origin.

PMID- 9240899
TI  - Timeliness of urinalysis: a College of American Pathologists Q-probes study of
      346 small hospitals.
AB  - OBJECTIVE: To explore preanalytic handling of urinalysis specimens. DESIGN: The
      study was a College of American Pathologists Q-Probes study consisting of two
      parts. The first part was a questionnaire about participants' urinalysis
      practices. The second part required collection of information from four specific
      urinalysis specimens per shift on 30 consecutive days or from 200 urine
      specimens, whichever occurred first. SETTING: Three hundred forty-six small
      hospitals enrolled in the Small Hospital Q-Probes program. MAIN OUTCOME MEASURES:
      Compliance with guidelines requiring nonrefrigeration and specimen measurement
      within 2 hours of collection, and identification of practices associated with
      better performance. RESULTS: Almost 50,000 urinalysis specimens were analyzed.
      About 68% of the specimens were measured without prior refrigeration, 2.3% were
      refrigerated before, 17.9% were refrigerated after, and 4.5% were refrigerated
      before and after arrival in the laboratory. Aggregate analysis indicated that
      11.2% of never-refrigerated specimens exceeded the recommended 2-hour time
      standard before analysis. For inpatients and outpatients, respectively, 64% and
      77% of laboratories were able to meet the 2-hour goal 90% of the time. Improved
      performance was associated statistically with ordering urinalysis stat, an
      enforced policy of specimen rejection for delayed transport of inpatient
      specimens, and the listing of a collection time for outpatient specimens.
      CONCLUSIONS: A large number of urinalysis specimens exceeded current quality
      guidelines for handling. Laboratories must monitor and improve preanalytic
      handling of urinalysis specimens.

PMID- 9240900
TI  - Protocol for the examination of specimens from patients with carcinoma of the
      ampulla of Vater: a basis for checklists. Cancer Committee, College of American
      Pathologists.
AB  - A protocol for the pathologic examination and reporting of specimens from
      patients with carcinoma of the ampulla of Vater has been developed by the Cancer
      Committee of the College of American Pathologists. The protocol incorporates all
      basic pathology data of diagnostic and prognostic significance appropriate for
      the treatment of patients with ampullary carcinoma. The purposes of the protocol
      are to serve as a basis for the development of checklists, as an outline for full
      narrative reporting, as a basis for research protocols, or as a guide for other
      types of synoptic or reporting formats. The protocol is stratified to accommodate
      the surgical procedures usually employed for carcinomas of the ampulla of Vater,
      including acquisition of cytologic specimens, incisional biopsy, excisional
      biopsy, and Whipple procedure (pancreaticoduodenectomy, partial or complete, with
      or without partial gastrectomy). Explanatory notes detailing specific procedures
      and rationales for documentation of specific pathologic data are included in the
      protocol. The protocol uses the staging system for carcinoma of the ampulla of
      Vater defined by the American Joint Committee on Cancer and the International
      Union Against Cancer.

PMID- 9240901
TI  - Optimized automated apolipoprotein A-I assays as markers for coronary artery
      disease.
AB  - BACKGROUND: Studies are divided as to whether or not apolipoprotein A-I (apo A-I)
      is a better marker for coronary artery disease (CAD) than high-density
      lipoprotein cholesterol. We hypothesized that the detergent Tween 20, which is
      thought to expose antigenic sites in apo A-I, would improve automated kit apo A-I
      assays as a diagnostic marker for CAD. METHODS: Apolipoprotein A-I was assayed by
      two standard automated methods and by the same methods after serum samples and
      reagents had been treated with Tween 20. Serum samples were obtained from 226
      consecutive male patients, age 40-70 years, presenting for angiography, except
      for defined exclusion characteristics. Patients were categorized into two groups
      on the basis of stenosis: (1) normal, all vessels <20% stenosis, n = 79, and (2)
      CAD, at least one vessel >70% stenosis, n = 147. Diagnostic accuracy was assessed
      by receiver operator characteristic stenosis curves and forward stepwise logistic
      regression, where adjustment was made for significant possible confounding
      characteristics and drugs. RESULTS: The optimal concentration of Tween 20 was
      found to be 0.5%. Receiver operator characteristic curves showed a greater area
      for apo A-I with Tween (area = 0.63 to 0.64) as compared to apo A-I without Tween
      (area = 0.60 to 0.62). Logistic regression indicated that apo A-I with Tween was
      a significantly better marker than high-density lipoprotein cholesterol. Receiver
      operator characteristic curves indicated that the ratio of modified apo A-I to
      apo B gave a significant improvement in area over the ratio of high-density to
      low-density lipoprotein cholesterol. CONCLUSIONS: Addition of Tween 20 to apo A-I
      assays improved diagnostic discrimination for CAD. The modified apo A-I assays
      were better markers than high-density lipoprotein cholesterol, and the ratio of
      apolipoproteins was significantly better markers than lipoprotein lipids. These
      findings may explain the discrepancies between studies comparing high-density
      lipoprotein cholesterol and apo A-I as markers for CAD. Our data suggest that a
      multicenter effort toward optimizing and clinically validating apo A-I test
      reagents may be worthwhile.

PMID- 9240903
TI  - Impact of managed care on the economics of laboratory operation in an academic
      medical center.
AB  - BACKGROUND: Throughout the 1980s, the number of laboratory tests performed in the
      United States grew at an annual rate of over 10%, and laboratory costs accounted
      for approximately 10% of overall health care expenditures. Recently, the
      influence of capitation, emphasis on cost-effectiveness, and changing roles among
      specialists and primary care physicians have begun to affect the growth of
      laboratory testing. We examined the impact of managed care on the economics of
      the clinical chemistry laboratory at Vanderbilt University Medical Center,
      Nashville, Tenn, to define the relative position of the clinical laboratory in
      the managed care environment of an academic medical center. METHODS: The
      following data were prospectively collected between fiscal years 1984/1985 and
      1995/1996: number of inpatients and outpatients, average length of stay, number
      of laboratory tests, total laboratory revenue, direct costs (consisting of salary
      and consumable costs), and number of full-time-equivalent (FTE) personnel. Using
      these data, we derived the following parameters: revenue and direct cost per
      patient, and revenue and productivity per FTE. RESULTS: Between 1984/1985 and
      1995/1996 the number of inpatients and outpatients increased 33% and 155%,
      respectively. Laboratory utilization, expressed as tests per patient, increased
      from 17 to 22 for inpatients between 1984/1985 and 1991/1992, and then sharply
      declined to 14.5 tests by 1995/1996, a 34% decrease compared with the 1991/1992
      level. Laboratory utilization for outpatients increased from 0.23 in 1984/1985 to
      0.45 tests in 1991/1992, decreased to 0.38 in 1993/1994, but then rose again to
      0.43 in 1995/1996. Total revenue more than doubled between 1984/1985 and
      1991/1992, mostly owing to increased inpatient revenue. Since 1992/1993,
      inpatient revenue has steadily declined, leading to a decrease in total revenue,
      which was partially offset by a continuous increase in outpatient revenue. In
      1995/1996, outpatient revenue accounted for 32.1% of total revenue, compared with
      7.7% in 1984/1985. Direct test cost per patient increased approximately 20%
      between 1984/1985 and 1991/1992, followed by a decline below the 1984/1985 level.
      The number of FTEs increased in parallel to the rising test volume through
      1991/1992 and subsequently was reduced in response to the decrease in test volume
      and productivity. In 1995/1996, a 22.7% reduction in staff was imposed despite an
      upward trend in test volume, resulting in a sharp increase in revenue and
      productivity per FTE. The staff reduction did not decrease direct laboratory
      costs, which have remained constant since 1992/1993. CONCLUSIONS: After three
      decades of continued growth, managed care has caused a sharp reversal in the
      upward trend in the number of laboratory tests, the number of tests per
      inpatient, test costs per patient, laboratory revenue, and productivity. A recent
      staff reduction significantly increased revenue and productivity per FTE, but
      showed no effect on direct laboratory costs.

PMID- 9240902
TI  - An erbium:YAG laser to obtain capillary blood samples without a needle for point
      of-care laboratory testing.
AB  - BACKGROUND: Needlestick injury poses an occupational hazard to health care
      workers that will increase with the increasing availability of point-of-care
      testing using capillary blood obtained with a lancet. OBJECTIVES: To demonstrate
      the safety and efficacy of a portable pulsed erbium:yttrium-aluminum-garnet
      (Er:YAG) laser in obtaining a blood sample from patients in a clinical setting
      and to determine whether the laser radiant energy alters the level of various
      components of blood, resulting in misleading laboratory results. DESIGN:
      Comparison of laboratory values of blood samples obtained with the laser and
      conventional lancet and comparison of patient and user preferences by
      questionnaire. PATIENTS AND METHODS: One hundred patients with diabetes mellitus
      attending a diabetes clinic were randomized to have capillary blood sampling from
      the fingertip performed either by the laser or a conventional lancet first, then
      with the other device. MAIN OUTCOME MEASURES: A comparison of pain, healing,
      hematocrit, and glycosylated hemoglobin (HbAlc), blood urea nitrogen, sodium,
      potassium, bicarbonate, and glucose levels. RESULTS: Adequate blood was obtained
      with both devices 97% of the time. Blood flow was greater with the laser
      perforation, resulting in higher operator preference. Although patients felt
      greater pain and experienced slower healing with the laser, these were not
      serious problems. Modification of the laser energy output led to a reduction in
      pain. Possibly owing to hemolysis, the potassium level in the blood obtained with
      the laser was significantly elevated and unsuitable for clinical decision making
      in many cases. None of the other measurements were similarly affected.
      CONCLUSIONS: We conclude that the laser device has the potential to obtain a
      blood sample for routine tests without a needle. This needle-free method will
      decrease the risk of bloodborne infections caused by needlestick injuries and
      thus lead to considerable cost savings and public health advantages. Further work
      is needed to alter the laser energy so that hemolysis can be decreased, thus
      enabling a more reliable potassium estimation.

PMID- 9240904
TI  - Sensitivity and cost-effectiveness of fine-needle aspiration with
      immunocytochemistry in the evaluation of patients with a pulmonary malignancy and
      a history of cancer.
AB  - OBJECTIVE: To determine the sensitivity and cost-effectiveness of transthoracic
      fine-needle aspiration in the separation of primary from metastatic malignancy.
      MATERIALS AND METHODS: Eighty-nine malignant pulmonary fine-needle aspirations in
      patients with a history of cancer were classified retrospectively by light
      microscopy, comparison with previous material, and immunocytochemistry. Decision
      analysis compared the cost-effectiveness of fine-needle aspiration, bronchoscopy,
      and thoracoscopy. RESULTS: Fine-needle aspiration classified 87% of the
      malignancies as primary (n = 7) or metastatic (n = 70) and 13% as indeterminate.
      By immunocytochemistry alone, 14 of 18 malignancies were subclassified. Decision
      analysis showed that pulmonary fine-needle aspiration with select use of
      thoracoscopy was more cost-effective than either bronchoscopy or thoracoscopy
      alone in many common clinical scenarios. CONCLUSIONS: Pulmonary fine-needle
      aspiration with immunocytochemistry is sensitive and cost-effective in
      subclassifying malignancies in patients with a history of cancer.

PMID- 9240905
TI  - Donor origin of posttransplant lymphoproliferative disorder localized to a liver
      allograft: demonstration by fluorescence in situ hybridization.
AB  - SETTING: Posttransplant lymphoproliferative disorders in solid organ
      transplantation are mostly of recipient origin. We report an unusual case of
      posttransplant lymphoproliferative disorder following liver transplantation with
      localized limited involvement of the solid organ allograft. DESIGN: Tissues were
      obtained at the time of surgery and evaluated by immunohistochemistry, in situ
      hybridization, and fluorescence in situ hybridization with chromosome X and Y
      centromeric probes. PATIENT: A 53-year-old Hispanic man with hepatic failure due
      to hepatitis C virus who underwent orthotopic liver transplant from a female
      donor and developed posttransplant lymphoma in the transplanted liver.
      INTERVENTION: Withdrawal of immunosuppression, resection of liver allograft, and
      second transplant. RESULTS: This posttransplant lymphoproliferative disorder was
      clearly shown to be derived from Epstein-Barr virus-infected donor lymphoid
      cells. This was demonstrated by fluorescence in situ hybridization for X and Y
      chromosomes in paraffin sections in a sex-mismatched transplant. Despite
      aggressive histology (monoclonal B-cell immunoblastic lymphoma) and lack of
      response to withdrawal of immunosuppression, the posttransplant
      lymphoproliferative disorder was successfully managed by repeat liver
      transplantation without recurrence. CONCLUSION: Fluorescence in situ
      hybridization was used to prove donor derivation in a posttransplant lymphoma of
      the liver. Allograft-localized donor posttransplant lymphoproliferative disorder
      may represent a unique category with more favorable prognosis requiring different
      clinical management from other cases.

PMID- 9240906
TI  - Blastic transformation of hairy cell leukemia.
AB  - OBJECTIVE: To report blastic transformation of hairy cell leukemia, an uncommon
      lymphoproliferative disorder of B-cell lineage. DESIGN: Routine histology,
      cytochemistry, and ultrastructural analysis were used to study this case.
      Immunoperoxidase studies for leukocyte common antigen (CD45), pan B-cell marker
      L26 (CD20), and hairy cell leukemia marker DBA.44 were performed. In addition,
      cell surface marker analysis for CD19, CD20, CD5, CD25, CD11c, and kappa and
      lambda light chains by flow cytometry was performed. RESULTS: The patient
      presented with typical clinical, morphologic, cytochemical, immunophenotypic, and
      ultrastructural features of hairy cell leukemia. Following splenectomy and prior
      to institution of any other therapy, he developed a blastic lymphoproliferative
      malignancy with loss of tartrate-resistant acid phosphatase activity, expression
      of cell surface markers CD11c and CD25, and immunoreactivity for DBA.44.
      CONCLUSION: We believe this to be the first report of such a transformation and
      recommend that the differential diagnosis of blastic transformation of chronic
      lymphoproliferative disorders include such a possibility.

PMID- 9240907
TI  - Histopathologic changes in human small intestine during storage in Viaspan organ
      preservation solution.
AB  - OBJECTIVE: To evaluate the histopathologic changes that occur in human small
      intestine or time when preserved in Viaspan organ preservation solution. DESIGN:
      Short segments of human small intestine were placed in standard organ
      preservation solution (Viaspan) and stored in conditions that mimic the clinical
      situation associated with clinical organ procurement, preservation, and
      transplantation. The intestinal segments were removed at sequential time points
      and placed in 10% formalin. Specimens underwent histopathologic examination to
      determine time-related changes. SPECIMENS: Short intestinal segments were
      obtained from seven multiorgan cadaver donors. Specimens were obtained in a way
      that exactly mimicked small intestinal organ retrieval. RESULTS: Small intestinal
      histology remained normal for the first 6 hours. After 6 hours, vacuolar
      separation began to occur between the epithelium and the basement membrane in the
      upper half of the villi. After 9 hours of cold preservation, epithelial
      detachment extended deep into the crypts with occasional shedding of cells and
      villi. CONCLUSIONS: Currently used small intestinal preservation using Viaspan
      results in considerable histopathologic changes in human jejunum after 9 hours of
      cold storage. The histopathologic pattern appears normal for the first 6 hours
      and suggests that preservation times should be limited to this time period when
      possible.

PMID- 9240908
TI  - Immunohistochemical analysis of human embryos and fetuses: an insight into the
      mechanism of subversion of antigenic differentiation in neoplasia.
AB  - OBJECTIVES: Immunohistochemical identification of intermediate filaments and
      other cell identity markers is of immense value in diagnostic tumor pathology.
      However, the literature contains many examples of inappropriate expression of
      markers by various tumors or coexpression of two or more markers supposedly
      specific for different cell types. The present study investigated this subversion
      of antigen differentiation in tumors by using developing tissues as a model.
      MATERIALS AND METHODS: Twenty-five human embryos and fetuses of 4 to 24 weeks'
      gestation were studied. An indirect immunoperoxidase method was applied to
      formalin-fixed, paraffin-embedded sections using a panel of 13 commonly used cell
      identity markers including intermediate filaments. RESULTS: During early
      development, vimentin was found to be coexpressed with cytokeratin in surface
      ectoderm, developing notochord, renal tubule epithelium, and intestinal mucosa.
      It coexpressed with glial fibrillary acidic protein in developing neuroglial
      tissue, with S100 in cartilage, and with skeletal muscle markers in myotubules.
      Hence, vimentin represents immaturity of tissues and is coexpressed with specific
      cell markers to be eventually replaced by the latter. Transbarrier expression of
      cytokeratin in smooth muscle was also noted. CONCLUSION: The aberrant expression
      of antigens in neoplastic tissues, as reported in the literature, simulates the
      varying expression of antigens in immature tissues during development. Hence, it
      is proposed that the phenomenon of antigenic subversion in neoplasia is related
      to the process of maturation and differentiation.

PMID- 9240909
TI  - Granulomatous prostatitis on needle biopsy.
AB  - OBJECTIVE: To assess pathologic findings of granulomatous prostatitis (GP) on
      needle biopsy. DESIGN: Ninety-four cases of granulomatous prostatitis were culled
      from 25,852 (incidence 0.36%) consecutive men who underwent needle biopsy;
      clinical correlations were obtained for 75. Cases were categorized as nonspecific
      (NSGP, 77.7%), infectious (IGP, 18.1%), or indeterminate (4.3%) granulomatous
      prostatitis based on histologic and clinical criteria. SETTING: Consecutive cases
      from a large commercial laboratory and consultation cases. RESULTS: All cases of
      IGP had a history of prior bacillus Calmette-Guerin therapy for transitional cell
      carcinoma. Histologically, 57% of NSGP cases mimicked infection and 4% mimicked
      cancer. Caseating necrosis was identified in 76% of cases of IGP. Significant
      numbers of eosinophils were found in 68% of NSGP cases, but in only 12% of IGP
      cases. In no case was eosinophilia documented in peripheral blood. Multinucleated
      giant cells were absent or rare in 69% of NSGP cases. Significant numbers of
      neutrophils were found in 53% of NSGP cases, but in only 29% of IGP cases. At the
      time of biopsy, cancer was clinically suspected in 55% of cases categorized as
      NSGP and 73% categorized as IGP. Serum prostate-specific antigen ranged from less
      than 0.5 ng/mL to 114 ng/mL (mean 12.7 ng/mL) in NSGP and from 0.9 ng/mL to 9.7
      ng/mL (mean 4.2 ng/mL) in IGP. Digital rectal exam was abnormal in 69% and 91% of
      NSGP and IGP cases, respectively. Transrectal ultrasound was abnormal in 77% and
      100% of NSGP and IGP cases, respectively. There was no correlation between the
      extent of core involvement with either clinical impression, prostate-specific
      antigen levels, transrectal ultrasound, or digital rectal exam. Thirty additional
      granulomatous prostatitis cases on needle biopsy were obtained from the
      consultation files of one of the authors. The major difference in this group was
      a higher percentage of cases histologically mimicking cancer (20%); two cases
      were misdiagnosed by the referring pathologist as high-grade cancer. CONCLUSIONS:
      While NSGP is the most common granulomatous prostatitis seen on needle biopsy,
      bacillus Calmette-Guerin granulomas are not seen infrequently. Lesser known
      histologic features of NSGP were the frequent finding of neutrophils and
      eosinophils and infrequent multinucleated giant cells. Granulomatous prostatitis
      may be clinically indistinguishable from cancer, and NSGP may also histologically
      mimic carcinoma.

PMID- 9240910
TI  - Clinical, biochemical, and morphologic investigations of a case of long-chain 3
      hydroxyacyl-CoA dehydrogenase deficiency.
AB  - We report the premortem and postmortem morphologic and histologic features and
      biochemical findings of a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase
      (L-CHAD) deficiency and compare these with those described in previously reported
      cases of L-CHAD deficiency. In addition to chronic nonketotic hypoglycemia,
      hypotonia, and liver failure, this patient had chronic hemolytic anemia and
      delayed central nervous system myelination. These features have not been
      previously documented in L-CHAD deficiency.

PMID- 9240911
TI  - Subclinical Cushing's syndrome due to adrenal myelolipoma.
AB  - We describe a patient with an incidental adrenal myelolipoma associated with
      biochemical evidence of Cushing's syndrome who lacked the physical stigmata of
      cortisol excess (subclinical Cushing's syndrome). Pathologic examination revealed
      the presence of adrenocortical cells mixed with myelolipomatous tissue. Although
      cases of clinically evident Cushing's syndrome due to adrenal myelolipomas have
      been reported previously, to our knowledge this is the first report associating
      adrenal myelolipoma and subclinical Cushing's syndrome.

PMID- 9240912
TI  - Autopsy findings of fatal complication of posterior cerebral circulation
      angioplasty.
AB  - Percutaneous transluminal angioplasty is a technique widely used to treat
      stenotic atherosclerotic lesions of the coronary arteries. This technique is
      currently gaining acceptance for the treatment of cerebral atherosclerotic
      disease. Autopsy findings of fatal complications of percutaneous transluminal
      angioplasty of the posterior cerebral circulation have, to our knowledge, not yet
      been published. We report the case of a patient with severe diffuse
      atherosclerosis of vertebral and basilar arteries, whose symptoms were not
      ameliorated with standard medical therapy. Transfemoral percutaneous transluminal
      angioplasty was performed in an attempt to reestablish blood flow in the
      posterior cerebral circulation by angioplasty of a severely stenotic basilar
      artery. The patient suffered a fatal complication during the procedure due to
      rupture of the basilar artery by the percutaneous transluminal angioplasty
      guidewire apparatus, leading to massive subarachnoid hemorrhage. We report the
      clinical and autopsy findings of this case.

PMID- 9240913
TI  - Disseminated congenital neuroblastoma involving the placenta.
AB  - Neuroblastoma, a tumor of primitive neuroectodermal cells, is one of the most
      common solid malignancies of neonates. Placental metastases have been described
      in rare cases of congenital neuroblastoma, usually in association with hydrops
      fetalis, placentomegaly, and widespread disease in the neonate. We report a case
      in which the unexpected diagnosis of neuroblastoma was made based on the
      postnatal finding of tumor emboli confined to fetal vessels of the placenta.
      Radiation and chemotherapy were given based on this diagnosis, obviating the need
      for an invasive diagnostic procedure.

PMID- 9240914
TI  - The College of American Pathologists, 1946-1996: laboratory accreditation.

PMID- 9240915
TI  - BRCA1: genetic testing and hereditary breast and ovarian cancer.

PMID- 9240916
TI  - Memories of microbes and metabolism.
AB  - As Jackie Gleason was wont to say: "How sweet it really is!" And--reflecting on
      the 1940s-1980s, when studies of microbial nutrition revealed exciting structure
      function relationships of the B-complex vitamins with relevance to metabolism in
      humans--it really is. A chemistry degree from Beloit College and a doctorate in
      biochemistry from the University of Wisconsin set the stage for my life's work at
      Lederle Laboratories, the University of Illinois, and Vanderbilt University. At
      Lederle my research contributed to folic acid chemistry: coenzyme forms and
      function; antimetabolites and cancer chemotherapy. My subsequent university
      studies centered on lysine biosynthesis and metabolism, e.g. its precursor role
      in carnitine and in indolizidine alkaloids of physiological interest. There were
      also many opportunities to reach out and give something back to the system via
      teaching and diverse service activities, all of which has led to a happy,
      fulfilling career, one for which I am ever thankful.

PMID- 9240917
TI  - Energy and protein requirements during lactation.
AB  - Additional energy needs for an exclusively breastfeeding woman are approximately
      670 kcal/day. If one allows for gradual weight loss, the net increment needed is
      about 500 kcal/day. There is little evidence of energy-sparing adaptations in
      basal metabolic rate or dietary-induced thermogenesis during lactation, although
      physical activity may be reduced during the early postpartum period. In women
      with adequate fat reserves, moderately negative energy balance is not likely to
      affect lactation. The recommended increment in protein intake during lactation
      has been estimated to be about 15 g/day, based on a milk protein concentration of
      11 g/liter. However, if one takes into account the protein cost of non-protein
      nitrogen in human milk, the recommended increment in protein is about 20 g/day.
      The latter value is consistent with data from nitrogen balance studies in
      lactating women. Low protein intakes are unlikely to affect milk volume but may
      alter certain fractions of milk nitrogen.

PMID- 9240918
TI  - Toxic and essential metal interactions.
AB  - Cadmium, lead, mercury, and aluminum are toxic metals that may interact
      metabolically with nutritionally essential metals. Iron deficiency increases
      absorption of cadmium, lead, and aluminum. Lead interacts with calcium in the
      nervous system to impair cognitive development. Cadmium and aluminum interact
      with calcium in the skeletal system to produce osteodystrophies. Lead replaces
      zinc on heme enzymes and cadmium replaces zinc on metallothionein. Selenium
      protects from mercury and methylmercury toxicity. Aluminum interacts with calcium
      in bone and kidneys, resulting in aluminum osteodystrophy. Calcium deficiency
      along with low dietary magnesium may contribute to aluminum-induced degenerative
      nervous disease.

PMID- 9240919
TI  - Development and biomedical testing of military operational rations.
AB  - This article gives a brief history of military nutrition research in this century
      and reviews recent advances made through field testing. Although modern rations
      are nutritionally complete, ration developers are challenged to improve
      palatability to promote increased intakes in field training and combat settings.
      The principal goal for military nutritionists is to identify the optimal
      macronutrient mix and specific ration components that sustain a soldier's
      performance in the face of operational stressors such as sleep deprivation,
      intense physical activity, climatic extremes, and hypobaric hypoxia. Energy
      expenditures during typical field-training exercises average approximately 4000
      kcal/day, whereas energy intakes are usually 3000 kcal/day or less when
      operational rations are consumed. One way to ameliorate the effects of this
      shortfall is to provide soldiers with a carbohydrate beverage supplement.

PMID- 9240920
TI  - Regulation of mammalian acetyl-coenzyme A carboxylase.
AB  - Long-chain fatty acids are involved in all aspects of cellular structure and
      function. For controlling amounts of fatty acids, cells are endowed with two
      acetyl-coenzyme A carboxylase (ACC) systems. ACC-alpha is the rate-limiting
      enzyme in the biogenesis of long-chain fatty acids, and ACC-beta is believed to
      control mitochondrial fatty acid oxidation. These two isoforms of ACC control the
      amount of fatty acids in the cells. Phosphorylation and dephosphorylation of ACC
      alpha cause enzyme inactivation and activation, respectively, and serve as the
      enzyme's short-term regulatory mechanism. Covalently modified enzymes become more
      sensitive toward cellular metabolites. In addition, many hormones and nutrients
      affect gene expression. The gene products formed are heterogeneous and tissue
      specific. The ACC-beta gene is located on human chromosome 12; the cDNA for this
      gene has just been cloned. The gene for the alpha-isoform is located on human
      chromosome 17. The catalytic core of the beta-isoform is homologous to that of
      the alpha-isoform, except for an additional peptide of about 150 amino acids at
      the N terminus. This extra peptide sequence makes the beta-form about 10,000
      daltons larger, and it is thought to be involved in the unique role that has been
      assigned to this enzyme. The detailed control mechanisms for the beta-isoform are
      not known.

PMID- 9240921
TI  - Nutrition screening in old people: its place in a coherent practice of preventive
      health care.
AB  - The central demographic reality of our times is the rapid aging of our society.
      Preventive nutritional and preventive health care of older people, therefore, are
      pressing issues that must be contended with. Several strategies for this are
      possible, including the broadcasting of general nutritional and health messages
      to the population, the inclusion of preventive nutrition and health as part of
      routine primary care, and nutrition screening: a process of self-identification
      by the older population in which they judge for themselves whether they are at
      nutritional risk and, if so, seek the care of professionals. This review focuses
      on some of the necessities for screening: sensitive, specific, and inexpensively
      applied screening devices; and explicit interventions that do not have major
      public health benefit for those who screen negative. Unfortunately, there is
      little evidence that screening is beneficial, nor have the benefits of this
      strategy been compared with its alternatives. Thus, the ethical imperative of
      screening has not been met: that because the activity is being promoted (it is
      not initiated by the public), its benefit must be conclusive.

PMID- 9240922
TI  - Lipolysis: contribution from regional fat.
AB  - In vitro studies of adipocytes taken from different body fat regions suggest
      substantial differences in lipolysis between intra-abdominal, lower-body
      subcutaneous, and abdominal subcutaneous regions. Gender and obesity appear to
      influence these regional differences. In situ measurements of glycerol release
      from adipose tissue provided further evidence that regional heterogeneity of
      lipolysis occurs in humans. In vivo studies of regional free fatty acid (FFA)
      release have confirmed that adipose tissue lipolysis varies between upper- and
      lower-body fat. Release of FFA from lower-body adipose tissue is less than that
      from upper-body adipose tissue in both obese and non-obese men and women. In non
      obese men and women, meal ingestion suppresses FFA release from all adipose
      tissue regions, and adrenergic stimulation activated FFA release from different
      sites in a gender-specific fashion. Significant regional and gender differences
      in adipose tissue lipolysis occur in humans, and this could contribute to
      differences in the health effects of adipose tissue and could theoretically
      influence body fat distribution.

PMID- 9240923
TI  - Structure and function of pancreatic lipase and colipase.
AB  - Dietary fats are essential for life and good health. Efficient absorption of
      dietary fats is dependent on the action of pancreatic triglyceride lipase. In the
      last few years, large advances have been made in describing the structure and
      lipolytic mechanism of human pancreatic triglyceride lipase and of colipase,
      another pancreatic protein that interacts with pancreatic triglyceride lipase and
      that is required for lipase activity in the duodenum. This review discusses the
      advances made in protein structure and in understanding the relationships of
      structure to function of pancreatic triglyceride lipase and colipase.

PMID- 9240924
TI  - Regulation of milk lipid secretion and composition.
AB  - Triacylglycerols make up 98% of the lipid content of milk, ranging in different
      species from 0 to 50% of the total milk volume. The fatty aid composition of the
      triacylglycerols depends on the species, the dietary fatty acid composition, and
      the carbohydrate-to-lipid ratio of the diet. The rate of lipid synthesis in the
      lactating mammary gland depends on the stage of mammary development and is
      decreased by fasting and starvation in ruminants and rodents but not in species
      that fast during lactation, such as seals and hibernating bears. Regulatory
      agents include insulin, prolactin, and non-esterified fatty acids. Dietary trans
      fatty acids may depress milk lipid synthesis under certain conditions. Evidence
      is presented that fatty acids may play a major regulatory role in acute changes
      in de novo mammary fatty acid synthesis, acting primarily on the activity of
      acetyl coenzyme A carboxylase.

PMID- 9240925
TI  - Energy sources and requirements of the exercising horse.
AB  - This review outlines the energy sources available to the horse, from its diet and
      from its body stores, at rest and while exercising. It looks at the current ways
      of describing the energy potential of diets fed to horses and discusses the
      relative advantages and disadvantages of the digestible energy and net energy
      systems. The more empirical net energy system for calculating the energy
      available for maintenance and work is compared with a more physiological
      partitioning system. Finally, the energy requirements for maintenance and
      exercise are discussed, together with how they may be practically determined and
      achieved through different diets.

PMID- 9240926
TI  - Evaluation of methodology for nutritional assessment in children: anthropometry,
      body composition, and energy expenditure.
AB  - Nutritional status in children is an indicator of health and well-being at both
      the individual and the population level. Screening for malnutrition should be an
      integral part of pediatric care universally. Nutritional intervention requires
      repeated measurement of nutritional status to assess severity and to track
      progress over time. Methodological issues in the assessment of nutritional status
      are reviewed with emphasis on anthropometric measurement, body composition, and
      energy expenditure of children at risk for malnutrition. Use of reference data,
      measurement error, maturational effects, and hereditary factors are among the
      issues reviewed and serve as guidelines in the interpretation of measurement of
      nutritional status.

PMID- 9240927
TI  - Taste preferences and food intake.
AB  - Sensory responses to the taste, smell, and texture of foods help determine food
      preferences and eating habits. However, sensory responses alone do not predict
      food consumption. The view that a "sweet tooth" leads to obesity through excess
      sugar consumption is overly narrow. In reality, there are multiple links between
      taste perceptions, taste preferences, food preferences, and food choices and the
      amount of food consumed. Taste responses are influenced by a range of genetic,
      physiological, and metabolic variables. The impact of taste factors on food
      intake further depends on sex and age and is modulated by obesity, eating
      disorders, and other pathologies of eating behavior. Food preferences and food
      choices of populations are further linked to attitudinal, social, and--probably
      most important--economic variables such as income. Nutrition education and
      intervention strategies aimed at improving population diets ought to consider
      sensory pleasure response to foods, in addition to a wide range of demographic
      and sociocultural variables.

PMID- 9240928
TI  - Emerging issues in microbiological food safety.
AB  - Many microorganisms previously unrecognized as food-borne or harmful are emerging
      as human pathogens transmitted by food. This is a result of recent acquisition of
      key virulence factors, detection by newly developed isolation procedures, or
      astute detective-like laboratory skills of microbiologists. Six microbial
      pathogens, including Shiga toxin-producing Escherichia coli, Listeria
      monocytogenes, Arcobacter butzleri, Helicobacter pylori, Cryptosporidium parvum,
      and Cyclospora, have become recognized as significant causes of human illness.
      Although the ecology and epidemiology of illness caused by some of these
      pathogens have not been fully elucidated, food has the potential of being an
      important vehicle in their dissemination. Existing technologies and new
      approaches such as irradiation and hazard analysis critical control point (HACCP)
      programs are useful tools in the control of food-borne hazards. However, because
      of ever-changing products, processes, food-handling practices, societal habits,
      and pathogens, emerging food-borne diseases will continue to be an important
      public health concern.

PMID- 9240929
TI  - Intracellular lipid-binding proteins and their genes.
AB  - Intracellular lipid-binding proteins are a family of low-molecular-weight single
      chain polypeptides that form 1:1 complexes with fatty acids, retinoids, or other
      hydrophobic ligands. These proteins are products of a large multigene family of
      unlinked loci distributed throughout the genome. Each lipid-binding protein
      exhibits a distinctive pattern of tissue distribution. Transcriptional control,
      regulated by a combination of peroxisome proliferator activated receptors and
      CCAAT/enhancer-binding proteins, allows for a variety of both cell and tissue
      specific expression patterns. In some cells, fatty acids increase the expression
      of the lipid-binding protein genes. Fatty acids, or their metabolites, are
      activators of the peroxisome proliferator-activated receptor family of
      transcription factors. Therefore, as the concentration of lipid in the diet
      increases, the expression of lipid-binding proteins coordinately increases. As
      revealed by X-ray crystallography, the lipid-binding proteins fold into beta
      barrels, forming a large internal water-filled cavity. Fatty acid ligands are
      bound within the cavity, occupying only about one-third of the accessible volume.
      The bound fatty acid is stabilized via a combination of enthalpic and entropic
      forces that govern ligand affinity and selectivity. Cytoplasmic lipid-binding
      proteins are the intracellular receptors for hydrophobic ligands, delivering them
      to the appropriate site for use as metabolic fuels and regulatory agents.

PMID- 9240930
TI  - The cholesterol-raising factor from coffee beans.
AB  - Some coffee brewing techniques raise the serum concentration of total and low
      density-lipoprotein cholesterol in humans, whereas others do not. The responsible
      factors are the diterpene lipids cafestol and kahweol, which make up about 1%
      (wt:wt) of coffee beans. Diterpenes are extracted by hot water but are retained
      by a paper filter. This explains why filtered coffee does not affect cholesterol,
      whereas Scandinavian "boiled," cafetiere, and Turkish coffees do. We describe the
      identification of the cholesterol-raising factors, their effects on blood levels
      of lipids and liver function enzymes, and their impact on public health, based on
      papers published up to December 1996.

PMID- 9240931
TI  - Mechanisms by which carbohydrates regulate expression of genes for glycolytic and
      lipogenic enzymes.
AB  - Regulation of gene expression by nutrients is an important mechanism in the
      adaptation of mammals to their nutritional environment. This is especially true
      for enzymes involved in the storage of energy, such as the lipogenic and
      glycolytic enzymes in liver and adipose tissue. Transcription of the genes for
      lipogenic and glycolytic enzymes is stimulated by glucose in adipose tissue,
      liver, and pancreatic beta-cells. Several lines of evidence suggest that glucose
      must be metabolized to glucose-6-phosphate to stimulate gene transcription. In
      adipose tissue, insulin increases the expression of lipogenic enzymes indirectly
      by stimulating glucose uptake. In the liver, insulin also acts indirectly by
      stimulating the expression of glucokinase and, hence, by increasing glucose
      metabolism. Glucose response elements have been characterized for the L-pyruvate
      kinase and S14 genes. They have in common the presence of a sequence 5'-CACGTG
      3', which binds a transcription factor called USF (upstream stimulatory factor).
      Another glucose response element, which uses a transcription factor named Sp1,
      has been characterized in the gene for the acetyl-coenzyme A carboxylase. The
      mechanisms linking glucose-6-phosphate to the glucose-responsive transcription
      complex are largely unknown.

PMID- 9240932
TI  - Dietary phytoestrogens.
AB  - Broadly defined, phytoestrogens include isoflavones, coumestans, and lignans. A
      number of these compounds have been identified in fruits, vegetables, and whole
      grains commonly consumed by humans. Soybeans, clover and alfalfa sprouts, and
      oilseeds (such as flaxseed) are the most significant dietary sources of
      isoflavones, coumestans, and lignans, respectively. Studies in humans, animals,
      and cell culture systems suggest that dietary phytoestrogens play an important
      role in prevention of menopausal symptoms, osteoporosis, cancer, and heart
      disease. Proposed mechanisms include estrogenic and antiestrogenic effects,
      induction of cancer cell differentiation, inhibition of tyrosine kinase and DNA
      topoisomerase activities, suppression of angiogenesis, and antioxidant effects.
      Although there currently are no dietary recommendations for individual
      phytoestrogens, there may be great benefit in increased consumption of plant
      foods.

PMID- 9240933
TI  - Use of drugs in the treatment of obesity.
AB  - Obesity has become an epidemic in the United States and in many other countries
      of the world. Obesity is a chronic disease, not a failure of willpower. Diet,
      exercise, and behavioral modification of lifestyle are rarely successful over the
      long term. Medications have been used sparingly, because of concerns about
      addiction and ineffectiveness, but used chronically, obesity drugs are effective.
      The two main categories of obesity drugs are centrally active adrenergic and
      serotonergic agents. These drugs reduce appetite, enhance satiety, and increase
      energy expenditure. Use of single agents produces modest weight loss and use of
      combinations increases loss, but few patients reach their goal weight. Co
      morbidities associated with obesity resolve or are reduced in severity with
      weight loss. Adverse events of major concern are changes in brain biochemistry
      and primary pulmonary hypertension. Published guidelines for use of obesity
      medications recommend they be used only for medically significant obesity.

PMID- 9240934
TI  - Regulation of the expression of lipogenic enzyme genes by carbohydrate.
AB  - Diets high in simple carbohydrates and low in fats lead in the mammalian liver to
      induction of a set of enzymes involved in lipogenesis. This induction occurs, in
      part, through transcriptional mechanisms that lead to elevated levels of the mRNA
      for these enzymes. For most of the lipogenic enzymes, an increase in glucose
      metabolism is required to trigger the transcriptional response. The intracellular
      mediator of this signaling pathway is unknown, although evidence suggests either
      glucose-6-phosphate or xylulose-5-phosphate. Studies to map the regulatory
      sequences of lipogenic enzyme genes involved in the transcriptional response have
      been performed for the L-type pyruvate kinase, S14, and acetyl-coenzyme A
      carboxylase genes. These studies have identified the DNA sequences necessary to
      link the signal generated by carbohydrate metabolism to specific nuclear
      transcription factors.

PMID- 9240935
TI  - Role of nutrition in prevention of the progression of renal disease.
AB  - In rats with renal disease, low-protein diets slow the decline in renal function,
      histologic damage, and mortality. Low-protein (and phosphorus) diets can also
      ameliorate uremic symptoms, secondary hyperparathyroidism, and metabolic acidosis
      in patients with chronic renal failure. Albeit controversial, evidence also
      suggests that dietary protein restriction can slow the rate of progression of
      renal failure and the time until end-stage renal failure. These dietary regimens
      appear to be safe and patients with chronic renal failure are able to activate
      normal compensatory mechanisms designed to conserve lean body mass when dietary
      protein intake is restricted. When low-protein diets are prescribed, patients
      should be closely monitored to assess dietary compliance and to ensure
      nutritional adequacy. Evidence that the spontaneous intake of dietary protein
      decreases in patients with progressive chronic renal failure who consume
      unrestricted diets should not be construed as an argument against the use of low
      protein diets. Rather, it is a persuasive argument to restrict dietary protein
      intake in order to minimize complications of renal failure while preserving
      nutritional status.

PMID- 9240936
TI  - Hormonal regulation of human muscle protein metabolism.
AB  - A continuous turnover of protein (synthesis and breakdown) maintains the
      functional integrity and quality of skeletal muscle. Hormones are important
      regulators of this remodeling process. Anabolic hormones stimulate human muscle
      growth mainly by increasing protein synthesis (growth hormone, insulin-like
      growth factors, and testosterone) or by decreasing protein breakdown (insulin).
      Unlike in growing animals, insulin's main anabolic effect on muscle protein in
      adult humans is an inhibition of protein breakdown. Protein synthesis is
      stimulated only in the presence of a high amino acid supply. A combination of the
      stress hormones (glucagon, glucocorticoids, and catecholamines) cause muscle
      catabolism, but the effects of the individual hormones on human muscle and their
      mechanisms of action remain to be clearly defined. Although thyroid hormone is
      essential during growth, both an excess and a deficiency cause muscle wasting by
      yet unknown mechanisms. A greater understanding of the regulation of human muscle
      protein metabolism is essential to elucidate mechanisms of muscle wasting.

PMID- 9240937
TI  - Role of blood flow in the regulation of muscle glucose uptake.
AB  - Insulin vasodilates skeletal muscle vasculature via an endothelium-derived nitric
      oxide-dependent mechanism. Data suggests that insulin interacts directly with the
      endothelium to cause nitric oxide release. This insulin-mediated increase in
      muscle perfusion accounts for approximately 30% of insulin's overall action to
      stimulate muscle glucose uptake, suggesting a role for insulin and glucose
      delivery as a determinant of insulin action. Hindlimb perfusion experiments,
      where perfusion rate is fixed, suggest that changes in distribution of
      microcirculatory perfusion can modulate substrate uptake. The potential role of
      insulin to enhance flow through capillary networks that are efficient at nutrient
      transfer to tissue (nutritive flow) relative to non-nutritive flow is discussed.

PMID- 9240938
TI  - Comparative nutrition of iron and copper.
AB  - The suggestion from nutritional studies with mammals of a link between iron and
      copper metabolism has been reinforced by recent investigations with yeast cells.
      Iron must be in the reduced ferrous (FeII) state for uptake by yeast cells, and
      reoxidation to ferric (FeIII) by a copper oxidase is part of the transport
      process. Thus, yeast cells deficient in copper are unable to absorb iron. In an
      analogous way, animals deficient in copper appear to be unable to move FeII out
      of cells, probably because it cannot be oxidized to FeIII. Invertebrate animals
      use copper and iron in ways very similar to vertebrates, with some notable
      exceptions. In the cases where vertebrates and invertebrates are similar, the
      latter may be useful models for vertebrate metabolism. In cases where they differ
      (e.g. predominance of serum ferritin in insects, oxygen transport by a copper
      protein in many arthropods, central importance of phenoloxidase, a copper enzyme
      in arthropods), the differences may represent processes that are exaggerated in
      invertebrates and thus more amenable to study in these organisms. On the other
      hand, they may represent processes unique to invertebrates, thus providing novel
      information on species diversity.

PMID- 9240939
TI  - Human body composition: advances in models and methods.
AB  - The field of human body composition research is reaching a mature stage in its
      development: The three interconnected areas that define body composition research
      -models and their rules, methodology, and biological effects--are well-defined
      and are actively investigated by scientists in diverse disciplines from many
      different nations; and methods are available for measuring all major atomic,
      molecular, cellular, and tissue-system level body composition components in
      research, clinical, and epidemiological settings. This review summarizes main
      body composition research concepts, examines new component-measurement
      methodologies, and identifies potential areas of future research.

PMID- 9240940
TI  - Applications of mass isotopomer analysis to nutrition research.
AB  - Investigations into regulating metabolic pathways with stable isotopes have, over
      the past decade, undergone major development with the use of nuclear magnetic
      resonance and mass spectrometry in studying labeling patterns of newly
      synthesized biomolecules. In this review, we concentrate on investigations of
      mass isotopomer distribution (MID) measured by mass spectrometry. We review the
      applications of MID to analytical problems, in particular the possibility of
      amplifying the measurement of low isotopic enrichments by incorporating multiple
      molecules or atoms of a primary analyte into the molecule of a secondary analyte,
      the MID of which is assayed. We also review new information on the regulation of
      intermediary metabolism gathered from the analysis of MID patterns of synthesized
      compounds. Lastly, we review the applications of MID to the synthesis of
      polymeric molecules, with emphasis on the validity of these techniques. A number
      of these techniques are applicable to investigations of nutrient metabolism in
      health and disease.

PMID- 9240941
TI  - Why do we eat? A neural systems approach.
AB  - Neuroregulators found at various brain sites are involved in controlling food
      intake, a behavior that occurs for many reasons. Different neuroregulators may
      affect different stimuli that impact eating behavior. For example, neuropeptide Y
      may initiate feeding for energy needs, opioid peptides may provide the rewarding
      aspects of eating, and corticotropin releasing factor may affect stress-induced
      eating. We know that the neural networks regulating feeding also impact other
      components of energy balance. Neuropeptide Y not only increases eating, it also
      decreases energy expenditure in brown fat and increases enzymatic activity
      associated with fat storage in white fat, resulting in a more obese animal. What
      the sites of action are of these neuroregulators and how they interact with
      regulators at other sites are of utmost importance. Different regions of the
      brain, together with the periphery, communicate via signals acting in coordinated
      fashion, which leads to the final outcome: eating less or more and expending less
      or more energy.

PMID- 9240942
TI  - Risk factors for bleeding in major abdominal surgery using heparin
      thromboprophylaxis.
AB  - BACKGROUND: Patients undergoing major abdominal surgery are at risk of both
      bleeding and thrombotic complications and usually receive heparin
      thromboprophylaxis. PATIENTS AND METHODS: Risk factors for perioperative bleeding
      were examined in 3,809 patients in a double-blind, randomized trial investigating
      heparin thromboprophylaxis. The risk factors were modeled by logistic regression,
      and a risk score was calculated using the significant factors in the model.
      RESULTS: Bleeding was associated with the following factors in the model, given
      as adjusted odds ratios (ORa [95% confidence interval]): male sex (ORa 1.68 [1.21
      to 2.34] P = 0.003), malignancy (ORa 1.69 [1.21 to 2.34] P = 0.008),
      gynecological surgery (ORa 1.62 [1.12 to 2.35] P = 0.011), and complex surgery
      (ORa 2.7 [2.02 to 3.62] P < 0.001). The risk of excessive bleeding for 0, 1, 2,
      and 3 risk factors was 2%, 6%, 11%, and 21%, respectively. CONCLUSIONS: The
      recognition of patients with these risk factors associated with perioperative
      bleeding should result in increased vigilance and may lead to modification of
      surgical and medical therapy.

PMID- 9240943
TI  - A study of forty-nine consecutive Whipple resections for periampullary
      adenocarcinoma.
AB  - BACKGROUND: We designed a program to evaluate the morbidity, mortality, survival
      rates, and patient's quality of life after Whipple resection for pancreatic and
      other periampullary adneocarcinoma. PATIENTS AND METHODS: After studying 11 fresh
      and unembalmed cadavers to learn the regional anatomy and to practice the
      surgical techniques for traditional Whipple procedure by the senior author (JS),
      49 patients aged 56 to 84 years old were treated with Whipple's
      pancreatoduocenectomy. RESULTS: There was no postoperative mortality or morbidity
      from anastomotic leakage. All 49 patients were discharged in an improved
      condition following surgery, including 5 patients with emergency resection. Eight
      patients are alive at the time of this writing, including 2 patients who had
      their pancreatic cancer resected 168 and 139 months ago. CONCLUSIONS: In the
      opinion of these authors, treatment of all resectable cancers with Whipple's
      pancreatoduodenectomy offers not only a superior palliation but also the hope of
      cure.

PMID- 9240944
TI  - Sphincter-saving resection, or not, for cancer of the midrectum.
AB  - BACKGROUND: The purpose of this study was to compare the time to pelvic
      recurrence and survival after sphincter-saving resection (SSR) or
      abdominoperineal resection (APR). METHODS: Out of the 119 patients with a cancer
      of the midrectum, 43 had undergone a SSR and 76 an APR for cure. To eliminate
      bias of a nonrandomized retrospective comparison, an adjustment for baseline
      prognostic covariates was used. RESULTS: Pelvic recurrence rates and survival
      distribution according to the type of resection did not differ significantly,
      with P values of 0.31 and 0.95, respectively, by the log-rank test. The Cox
      regression model incorporated nine binary covariates and the treatment group.
      Given these nine covariates, treatment did not influence either pelvic recurrence
      (adjusted P value = 0.62, relative risk = 0.78) or overall survival (adjusted P
      value = 0.89, relative risk = 1.05). CONCLUSION: These results suggest that, in
      patients with cancer of the midrectum treated by SSR or APR, recurrence and
      survival rates are similar.

PMID- 9240945
TI  - Expanded polytetrafluoroethylene patches used in the intraperitoneal or
      extraperitoneal position for repair of incisional hernias of the anterolateral
      abdominal wall.
AB  - BACKGROUND: Few large studies of the use of expanded polytetrafluoroethylene
      (ePTFE) in incisional hernia repairs have been done. We performed such a study of
      ePTFE patches implanted extraperitoneally or intraperitoneally. METHODS: The
      records of all patients in whom an ePTFE patch was used to repair an incisional
      hernia in 1987 to 1994 were reviewed retrospectively. RESULTS: An ePTFE patch was
      implanted in 158 patients, extraperitoneally in 98 and intraperitoneally in 60.
      There were no perioperative deaths. Serious postoperative complications,
      including 3 cases of sepsis (intraperitoneally placed patch), occurred in 6
      patients (4%). With a mean follow-up of 37 months (range 12 to 90), there were 2
      cases of late sepsis (with an extraperitoneal patch) and 6 recurrences (4 with an
      intraperitoneal patch). CONCLUSIONS: The ePTFE prostheses used in incisional
      hernia repair are well tolerated in the intraperitoneal position. Their
      effectiveness in the extraperitoneal position may be comparable to that of mesh
      but with a lower rate of sepsis.

PMID- 9240946
TI  - Feasibility of mathematical models to predict success in video-assisted thoracic
      surgery lung nodule excision.
AB  - BACKGROUND: Pulmonary nodules are occasionally difficult to excise using video
      assisted thoracic surgery (VATS). METHODS: To predict operative success,
      mathematical models using preoperative computerized tomography (CT) measurements
      were tested in 50 consecutive patients who underwent attempted or successful
      thoracoscopic lung biopsy. Unrelated technical problems resulted in the exclusion
      of 3 patients. RESULTS: No differences were noted with respect to lobar location,
      thoracic dimensions, gender, presence of chronic obstructive pulmonary disease,
      or nodule pathology. The expression S/(D + 1), where S = nodule size (cm) and D =
      distance (cm) to the nearest visceral pleura, yielded significantly higher values
      for visible nodules (P < 0.001). Resectable nodules had a higher score using the
      expression 1/(S + D + 1), (P < 0.001). Simple cases (n = 19) were defined as
      those in which nodules were both visible and resectable with very basic VATS
      techniques. All others (n = 28) were considered complex. The derived expression
      for Simplicity [1/(S(D + 1))] yielded significantly higher values for simple
      cases (0.8 +/- 0.3 vs. 0.3 +/- 0.2 cm(-2), P < 0.001) and all simple cases had a
      score > or = 0.4. Logistic regression analysis showed that the formulas for
      resectability and simplicity were significant independent predictors for
      resectability and simplicity. CONCLUSIONS: Equations based on objective CT
      measurements may be useful for planning VATS nodulectomy or studying the outcome
      of these minimally invasive operations.

PMID- 9240947
TI  - Selective arterial embolization for the control of lower gastrointestinal
      bleeding.
AB  - BACKGROUND: Transcatheter embolization is accepted as a safe method for treating
      acute bleeding from the upper gastrointestinal (GI) tract. Hesitancy persists
      using this technique below the ligament of Treitz, based on the belief that the
      risk of intestinal infarction is unacceptably high, despite mounting clinical
      evidence to the contrary. METHODS: A series of 17 consecutive patients with
      angiographically demonstrated small intestinal or colonic bleeding was
      retrospectively reviewed. The success and complication rate of subselective
      embolization was assessed. RESULTS: Bleeding was stopped in 13 of 14 patients
      (93%) in whom embolization was possible, and in 13 of 17 patients (76%) where
      there was an intention to treat. Sufficiently selective catheterization to permit
      embolization could not be achieved in 3 patients. No clinically apparent bowel
      infarctions were caused. CONCLUSION: Subselective embolization is a safe
      treatment option for lower GI bleeding, suitable for many patients and effective
      in most. Careful technique and a readiness to abandon embolization when a
      suitable catheter position cannot be achieved are important.

PMID- 9240948
TI  - Effect of intra-arterial environment on endothelialization and basement membrane
      organization in polytetrafluoroethylene grafts.
AB  - PURPOSE: To determine if a complete intra-arterial environment affects
      endothelialization rate and basement membrane organization in
      polytetrafluoroethylene (PTFE) grafts. METHOD: Thirty dogs underwent either
      infrarenal abdominal aorta PTFE interposition (12) or intraluminal stented (18)
      grafting. Grafts were explanted at 4 and 8 weeks and rate of endothelial ingrowth
      calculated. Endothelial cells were identified and basement membrane organization
      assessed using antibodies against endothelial cell-specific surface antigen CD31,
      type IV collagen, and laminin. RESULTS: Endothelialization rates, expressed as
      percent graft surface area coverage per week, were 3.7% +/- 0.62% (4-week
      control), 12.9% +/- 0.58% (4-week stented), 4.2% +/- 0.62% (8-week control), and
      10.0% +/- 0.54% per week (8-week stented grafts). Endothelial repaving rates were
      constant for control and increased in all stented grafts (P <0.01). At 4 weeks,
      laminin was identified in all control (6 of 6) and no stented grafts. Staining
      was confined to the 20% of the hyperplastic intimal area immediately below the
      endothelium. At 4 weeks, type IV collagen was present throughout the entire
      hyperplastic intima in control specimens but was confined to a discrete
      subendothelial zone in stented grafts. By 8 weeks, type IV collagen became
      concentrated in the luminal one third of the intima in control grafts.
      CONCLUSION: Intra-arterial graft location is associated with early formation of
      an organized basement membrane and accelerated endothelialization in PTFE grafts.

PMID- 9240949
TI  - Magnetic resonance-cholangiopancreatography in the diagnosis of biliopancreatic
      diseases.
AB  - BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a new,
      noninvasive imaging technique for the visualization of the biliary ducts with
      cholangiographic images similar to those obtained with endoscopic retrograde
      cholangiopancreatography and percutaneous transhepatic cholangiography. No
      contrast medium injection is used. The aim of this study was to assess the
      feasibility of MRCP versus ERCP in the diagnosis of biliary tract and pancreatic
      diseases. PATIENTS AND METHODS: One hundred and thirty-six patients were
      submitted to MRCP. They were referred to MR study according to four inclusion
      criteria: (1) evidence or suspicion of choledocholithiasis, (2) benign or
      malignant bile ducts stenosis, (3) follow-up of patients submitted to biliary
      enteric anastomosis, and (4) chronic pancreatitis with Wirsung duct dilatation.
      The MRCP was performed with a 0.5T superconducting magnet (Philips Gyroscan T5).
      When neoplastic disease was detected, additional images on axial planes were
      acquired. MRCP allowed images of diagnostic value to be obtained in all the
      cases. RESULTS: In choledocholithiasis, MRCP showed 91.6% sensitivity, 100%
      specificity, and overall diagnostic accuracy 96.8%. Of 48 patients with stenotic
      lesions, 16 were correctly characterized as benign and 30 as malignant. Two cases
      of focal chronic pancreatitis were misdiagnosed as pancreatic head carcinoma. In
      the patients submitted to biliary-enteric anastomosis, MCRP was able to detect
      the dilatation of the intrahepatic ducts, the stenosis, and associated stones in
      all 8 positive cases. In the remaining 7 patients with mild signs of cholangitis,
      MCRP showed irregular aspects of the biliary tree in the main ducts. In the 11
      patients with chronic pancreatitis, MCRP was able to depict the dilated Wirsung
      duct and the stenotic tract, although the fine details of the secondary ducts
      were not evaluated due to the low spatial resolution as compared with
      conventional films. CONCLUSIONS: MRCP can be considered a technique able to
      completely replace diagnostic ERCP. Further studies are necessary for a better
      evaluation of the potential advantages and disadvantages of this technique.

PMID- 9240950
TI  - The influence of ischemic bowel wall damage on translocation, inflammatory
      response, and clinical course.
AB  - BACKGROUND: While vascular patency and overall viability of the gut can be
      evaluated perioperatively, damage to the mucosal barrier can hardly be judged in
      the perioperative setting and, moreover, will probably determine the clinical
      course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical
      course was correlated to the severity of the disease (APACHE II; Septic Severity
      Score, SSS), the intraabdominal and systemic inflammatory response, and the
      translocation of bacteria and endotoxin. RESULTS: The comparison of the 10
      survivors with the nonsurviving group revealed no differences as to the length of
      history, serum lactate levels, white blood cell counts, body temperature, markers
      of the inflammatory response, or quantity and macroscopic quality of the exudate.
      Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative
      predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate
      (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P =
      0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II
      (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of
      ischemic bowel wall necrosis seems to depend on the severity of the disease at
      admission and on the integrity of the mucosal barrier rather than on inflammatory
      response, therapeutic measures, or supportive treatment.

PMID- 9240951
TI  - Roux-Y choledochojejunostomy and duodenojejunostomy for the complicated duodenal
      diverticulum.
AB  - BACKGROUND: Exclusion of the duodenum by means of transection and Roux-Y
      duodenojejunostomy has been practiced for the treatment of complicated duodenal
      diverticulum. However, this method does not divert bile away from the
      diverticulum, hence the possibility of pancreaticobiliary complications is not
      eliminated. METHODS: Roux-Y choledochojejunostomy and duodenojejunostomy, for the
      diversion of bile and food, has been applied for the treatment of
      pancreaticobiliary complications of duodenal diverticulum in 4 patients.
      Postoperatively, all patients had endoscopy, HIDA-scintigraphy for the
      measurement of enterogastric reflux, and assessment of gastric emptying. RESULTS:
      One year postoperatively, there were no recurrent symptoms of cholangitis or
      pancreatitis, no anastomotic ulceration was found on endoscopy, there were no
      complaints of gastric stasis, and enterogastric reflux was not significant.
      CONCLUSIONS: Roux-Y choledochojejunostomy and duodenojejunostomy for the
      treatment of the complicated duodenal diverticulum is associated with
      satisfactory results. Postoperative symptoms attributed to anastomotic
      ulceration, bile reflux, or gastric stasis are also absent.

PMID- 9240952
TI  - Clinicopathological features of superficial squamous cell carcinoma of the
      esophagus.
AB  - BACKGROUND: The depth of penetration is the crucial factor determining the
      prognosis of esophageal carcinoma patients. Patients with superficial esophageal
      carcinoma have a significantly favorable clinical course compared with those with
      advanced cancers. The outcome for patients with mucosal cancer is excellent with
      a 5-year survival rate exceeding 80%. On the other hand, submucosal cancer often
      metastasizes to lymph nodes or other organs, and the prognosis of these patients
      is far from satisfactory. METHODS: Among 165 patients with squamous cell
      carcinoma of the esophagus, surgically resected between December 1979 and April
      1995, 30 patients (18.2%) had superficial esophageal carcinoma (SEC) confined to
      the epithelium, lamina propria mucosa, or submucosa. Disease profile and
      clinicopathological characteristics of these 30 patients were studied. RESULTS:
      The incidence of SEC has increased from 6.3% (2 of 32) in the first 5-year period
      (1979 to 1984) to 27.4% (20 of 73) in the recent 5-year period (1991 to 1995).
      Subjective symptoms were present in 2 (13.3%) with 15 mucosal cancers and in 4
      (26.7%) with 15 submucosal cancers. The remaining 24 patients (80%) had no
      subjective symptoms. Twenty-two patients (73.3%) were diagnosed to have the
      lesions by endoscopic examination at the time of screening for gastric problems,
      and only 3 were detected by gastrointestinal series. None of the 15 patients with
      mucosal cancer had lymphatic invasion, venous invasion, or lymph node metastasis.
      On the other hand, in those with submucosal cancers, 9 (60%) had lymphatic
      invasion, 5 (33.3%) venous invasion, and 8 (53.3%) lymph node metastases. Twenty
      two patients are alive without recurrence. The 3- and 5-year survival rates are
      86.7% and 86.7% for patients with mucosal cancer and 72.2% and 65.0% for those
      with submucosal cancer, respectively. CONCLUSION: Esophagectomy with wide
      lymphadenectomy should be carried out for submucosal cancer, whereas
      esophagectomy with moderate lymphadenectomy can be preferred for mucosal cancer.

PMID- 9240953
TI  - A unified approach to the surgical exposure of pancreatic and duodenal injuries.
AB  - One of the greatest challenges to any surgeon is the intraoperative detection and
      surgical management of duodenal and pancreatic injuries. A uniform approach to
      the surgical exposure of all suspected pancreatic and duodenal injuries will
      decrease their morbidity and mortality by identifying all injuries. Proper
      intraoperative assessment and grading will help with procedure selection from the
      broad surgical armamentarium available to manage these injuries.

PMID- 9240954
TI  - An improved technique for a stapled transabdominal esophagojejunostomy.
AB  - BACKGROUND: In the performance of a stapled transabdominal esophagojejunostomy
      there are two main technical problems involved and related to a difficult
      surgical exposure. One is the placement of the purse-string suture and the second
      is the insertion of the anvil of the circular intraluminal stapler into the
      distal esophagus. METHODS: These technical difficulties can be overcome by
      opening just the anterior wall of the esophagus at the anastomosis level, leaving
      the posterior wall intact. RESULTS: The integrity of the posterior wall avoids
      retraction of the mucosa, allowing the esophagus to remain opened for the
      placement of a through and through purse-string suture under direct vision. It
      also acts as a conduit for the insertion of the anvil of the circular
      intraluminal stapler. CONCLUSIONS: The technique described herein avoids stay
      sutures, purse-string instruments, and forceful instrumental dilatation of the
      distal esophagus, making these very important operative steps much easier, safer,
      and more reliable.

PMID- 9240955
TI  - An objective assessment of laparoscopic antireflux surgery.
AB  - BACKGROUND: Complicated gastroesophageal reflux disease (GERD) requires long-term
      medical therapy, which in some instances is incompletely effective or poorly
      tolerated. Additionally, there is concern about the consequences of prolonged
      acid suppression therapy. Surgical correction of GERD has been a therapeutic
      option for decades. With the advent of video-assisted laparoscopic surgery,
      antireflux surgery has had a resurgence in popularity. PATIENTS AND METHODS:
      Between October 1992 and June 1995, 20 patients who underwent laparoscopic
      antireflux surgery were completely studied preoperatively and 3 months
      postoperatively with 24-hour pH monitoring and esophageal manometry. Follow-up
      averaged 18 months. The indication for surgery was medically refractory disease
      in 75%, intolerance to medication in 10%, and concern regarding the consequences
      of long-term medical therapy in 15%. Two thirds of these patients had complicated
      GERD. RESULTS: Operative time averaged 4 hours. There was no conversion to an
      open procedure. There was no mortality. Two patients had recurrent reflux, for a
      failure rate of 10%. Overall, postoperative reflux episodes and percent of time
      pH was less than 4 dropped significantly. Lower esophageal sphincter function
      showed a statistically significant increase in mean postoperative resting
      pressure and residual sphincter pressure during swallowing. There was no change
      in motility postoperatively. CONCLUSIONS: Laparoscopic antireflux surgery is a
      safe, effective, therapeutic alternative in the management of gastroesophageal
      reflux disease.

PMID- 9240956
TI  - Management of choledocholithiasis in the time of laparoscopic cholecystectomy.
AB  - BACKGROUND: The best way to detect and manage common duct stones in conjunction
      with laparoscopic cholecystectomy is not agreed upon at the present time.
      PATIENTS AND METHODS: Our experience with choledocholithiasis in a consecutive
      series of 1,123 cholecystectomies (94% by laparoscopy) has been reviewed.
      Suspected duct stones were investigated preoperatively or postoperatively by
      endoscopic retrograde cholangiography (ERC), and if necessary, duct clearance was
      attempted by endoscopic sphincterotomy (ES). No attempt was made to identify
      choledocholithiasis intraoperatively. RESULTS: Endoscopic retrograde
      cholangiography was performed in 11% of patients, and 32% of these required ES.
      The complication rate of ERC and ES was 8%, without mortality. Two patients
      required a second operation for missed choledocholithiasis, for a reoperation
      rate of 0.2%. CONCLUSION: We believe that primary or secondary open surgery is
      only occasionally necessary for the management of choledocholithiasis.
      Preoperative ERC and ES for suspected duct stones, with the same strategy
      employed as a salvage for stones presenting after cholecystectomy, was safe and
      efficient.

PMID- 9240957
TI  - Obturator hernia is an unsuspected diagnosis.
AB  - BACKGROUND: We present 6 patients with obturator hernia, from Harbor-UCLA Medical
      Center and Natalspruit Hospital, South Africa, bringing the total in the English
      literature to 676. This study was undertaken to examine the pitfalls in diagnosis
      and methods of treatment of this highly fatal condition. PATIENTS: All patients
      were women, with an average age of 79 years. All were emaciated and in poor
      general condition, with dementia (4 patients), airway disease (3), cardiac
      disease (3), and disseminated carcinoma (1). For 5 of the 6 patients, the
      diagnosis was made at laparotomy. One patient died postoperatively. RESULTS: The
      diagnosis was made from a lump in the upper thigh, felt vaginally or rectally,
      and a positive Howship-Romberg and/or a Hannington-Kiff sign. Radiographs,
      contrast studies, computed tomography scans, and herniography are helpful in
      making a diagnosis. In an emergency situation, lower midline laparotomy is
      preferred. Electively, other procedures and laparoscopic repair may be performed.
      CONCLUSION: Mortality (10% to 50%) is common due to the poor condition of the
      patients and the delay in diagnosis. Earlier diagnosis may lower the high
      morbidity and mortality associated with this condition.

PMID- 9240958
TI  - Preoperative diagnosis of strangulated obturator hernia using ultrasonography.
AB  - BACKGROUND: Obturator hernia is rarely recognized before surgical intervention,
      since it is relatively infrequent and its definitive diagnosis is difficult. To
      change this situation, we introduced ultrasound examination in 1993 for
      differential diagnosis of strangulated obturator hernia among patients with bowel
      obstruction of unknown cause. PATIENTS AND METHODS: Between 1993 and 1995, we
      encountered 15 patients with suspected obturator hernia based on the presence of
      bowel obstruction of unknown cause and so-called predisposing factors. These
      patients underwent ultrasound examinations. RESULTS: The 4 patients with bowel
      obstruction caused by strangulated obturator hernia were all correctly diagnosed
      preoperatively by ultrasonography and were successfully cured by surgery. The
      time required for diagnosis was shorter than reported previously (average 16.5
      h). CONCLUSIONS: Ultrasonography is useful and reliable for the diagnosis of
      strangulated obturator hernia and can decrease the morbidity and mortality
      associated with delayed diagnosis.

PMID- 9240959
TI  - Canine intestinal myoelectric activity after open versus laparoscopically
      assisted right hemicolectomy.
AB  - BACKGROUND: It is a common belief that a laparoscopic procedure results in a
      shorter duration of postoperative ileus compared with the equivalent open
      procedure. This study was undertaken to determine whether laparoscopically
      assisted right hemicolectomy in the dog results in a shorter duration of ileus
      compared with open right hemicolectomy. METHODS: Eight bipolar serosal electrodes
      (4 on the small bowel, 4 on the left colon) were implanted in each dog (n = 10).
      Three weeks after electrode implantation baseline recording was made for 5 days;
      then 5 dogs underwent laparoscopically assisted right hemicolectomy and 5
      underwent open right hemicolectomy. Myoelectric activity was recorded
      continuously for 72 hours postoperatively. Tracings were analyzed for the time of
      reappearance, duration, migration velocity, and cycle length of phase 2, phase 3,
      and the migrating colonic complex. The criteria used for the resolution of
      postoperative ileus were the return of phase 2, phase 3, and the migrating
      colonic complex. RESULTS: All dogs had temporary loss of organized myoelectric
      activity postoperatively. The mean reappearance time (minutes +/- standard
      deviation) for phase 3 was 857 +/- 574 versus 761 +/- 600; the phase 2
      reappearance time was 1,845 +/- 610 versus 1,590 +/- 668; and the migrating
      colonic complex reappearance time was 534 +/- 365 versus 572 +/- 552, open versus
      laparoscopically assisted right hemicolectomy, respectively. The times were not
      different (Wilcoxon rank sum test, P > 0.05). The time required for phase 3,
      phase 2, and the migrating colonic complex to attain preoperative configuration
      also was not different between the open and laparoscopically assisted group.
      CONCLUSION: Myoelectric resolution of postoperative ileus did not occur earlier
      in the dog undergoing laparoscopically assisted right hemicolectomy compared to
      the dog undergoing open right hemicolectomy. This data does not support the
      hypothesis that a laparoscopically assisted colectomy results in a shorter
      duration of postoperative ileus than the equivalent open procedure.

PMID- 9240960
TI  - Results of arteriovenous fistula revision in the forearm.
AB  - PURPOSE: We assessed the usefulness of revision for hemodialysis arteriovenous
      fistulae. METHODS: From 1985 to 1994, 287 arteriovenous fistulae were created at
      our facility. "Primary" patency was defined as the duration of fistula patency
      without revision, and "secondary" patency was defined as the duration of fistula
      patency after successful revision in the forearm not requiring prosthesis.
      RESULTS: The secondary patency rate was significantly better than the primary
      patency rate (89% versus 41% at 5 years, P < 0.01). The secondary patency rate in
      diabetic patients did not differ from that in nondiabetics, although there was a
      significant difference in the primary patency rate between these two patient
      groups (diabetics 30% versus nondiabetics; 45% at 5 years, P < 0.01).
      CONCLUSIONS: Revision is a reliable procedure for salvaging a failed fistula,
      which yields an acceptable patency rate regardless of the patient's risk factors
      for arteriosclerosis.

PMID- 9240961
TI  - Splenic abscesses from 1987 to 1995.
AB  - BACKGROUND: Isolated splenic abscesses is an uncommon clinical entity that is
      being increasingly recognized as a cause of intraabdominal sepsis in a wide
      variety of clinical situations, and involving a wide range of organisms. The
      increasing incidence of immunosuppressed states in this decade due to the use of
      chemotherapy for oncology, immunosuppression therapy for transplantation, and
      acquired immune deficiency syndrome, has changed the disease pattern of splenic
      abscesses. METHOD: Data from 287 cases reported in the English literature between
      1987 and 1995 were collected, analyzed, and compared with two previous reviews of
      cases reported before 1987. RESULTS: Staphylococcus, Salmonella, and Escherichia
      coli are the most common organisms cultured. Immunosuppressed states were present
      in 33.5% of cases, with intravenous drug abuse and acquired immune deficiency
      syndrome accounting for half these cases. Computerized tomography and
      ultrasonography are diagnostic, with a sensitivity of 92.2% and 87.2%,
      respectively. Nonoperative management has a success rate of less than 65%, but
      salvage splenectomy does not increase mortality compared with splenectomy as
      initial therapy. CONCLUSIONS: Splenic abscesses are increasingly recognized with
      immunosuppressed states. Percutaneous radiologically guided drainage may be
      suitable in some cases, but splenectomy with appropriate antibiotics is the
      definitive treatment.

PMID- 9240962
TI  - Health care for research animals is essential and affordable.

PMID- 9240963
TI  - Advances in adenoviral vectors: from genetic engineering to their biology.
AB  - Ad2 and Ad5 belong to a group of human cytolytic viruses that target the
      respiratory airways for reproduction, whereas latent infections establish within
      other tissues. Signals therefore exist that control this dichotomic process in
      different cell types, perhaps including cis and/or trans elements of viral
      origin. Since 1993, Ad2- and Ad5-based adenoviruses lacking all or part of the E1
      regulatory region have been undergoing evaluation in phase I trials that target
      cancer and cystic fibrosis. These viruses are extremely attenuated and actually
      do not reproduce in most human cells. However, they retain most of the virus
      genetic program and often promote a significant cytotoxicity after infection,
      emphasizing the need to further cripple the virus biology to extend the duration
      of transgene expression, if required. We will review the strategies currently
      followed to engineer a professional lytic virus for epithelial cells into an
      innocuous gene delivery vehicle. Potential effects on the transducing properties
      of the vector that may result from the inactivation of viral activities that
      normally allow/regulate extrachromosomal gene expression during wild-type
      infection are discussed.

PMID- 9240964
TI  - Adenoviral/retroviral vector chimeras: a novel strategy to achieve high
      efficiency stable transduction in vivo.
AB  - Gene therapy to correct defective genes requires efficient gene delivery and long
      term gene expression. Realization of both goals with available vector systems has
      so far not been achieved. As a novel approach to solve this problem, we have
      developed a chimeric viral vector system that exploits favorable aspects of both
      adenoviral and retroviral vectors. In this schema, adenoviral vectors induce
      target cells to function as transient retroviral producer cells in vivo. The
      progeny retroviral vector particles can then effectively achieve stable
      transduction of neighboring cells. In this system, the nonintegrative adenoviral
      vector is rendered functionally integrative via the intermediate generation of an
      induced retroviral producer cell. Such chimeric vectors may now allow realization
      of the requisite goals for specific gene therapy applications.

PMID- 9240965
TI  - Gene therapy for newborns.
AB  - Application of gene therapy to treat genetic and infectious diseases may have
      several advantages if performed in newborns. Because of the minimal adverse
      effect of the underlying disease on cells of the newborn, the relatively small
      size of infants, and the large amount of future growth, gene therapy may be more
      successful in newborns than in older children or adults. The presence of
      umbilical cord blood from newborns provides a unique and susceptible target for
      the genetic modification of hematopoietic stem cells. In our first trial of gene
      therapy in newborns, we inserted a normal adenosine deaminase gene into umbilical
      cord blood cells of three neonates with a congenital immune deficiency. The trial
      demonstrated the successful transduction and engraftment of stem cells, which
      continue to contribute to leukocyte production more than 3 years later. A similar
      approach may be taken to insert genes that inhibit replication of HIV-1 into
      umbilical cord blood cells of HIV-1-infected neonates. Many other metabolic and
      infectious disorders could be treated by gene therapy during the neonatal period
      if prenatal diagnoses are made and the appropriate technical and regulatory
      requirements have been met.

PMID- 9240966
TI  - Hematological malignancies.
AB  - The present cure rate for leukemia and lymphoma represents one of the success
      stories of modern cancer therapy. However, treatments remain toxic, expensive,
      and ineffective for many patients. There is therefore considerable interest in
      exploring gene therapies for these disorders. To date, four major strategies have
      been adopted: 1) modifying the tumor cell itself either by "repairing" one or
      more genetic defect associated with the malignant process, introducing a gene
      that will trigger an anti-tumor immune response, or delivering a pro-drug
      metabolizing enzyme that will render the tumor sensitive to the corresponding
      cytotoxic agent; 2) modifying the immune response to the tumor by altering the
      specificity or effector function of immune system cells; 3) decreasing the
      sensitivity of normal host tissue by delivering cytotoxic drug resistance genes
      to marrow precursor cells and thereby increasing the therapeutic index of
      cytotoxic agents; and 4) marking normal and malignant hemopoietic cells in order
      to more closely monitor the efficacy of conventional therapies. Given the current
      "state of the art," all these approaches have significant limitations, but each
      has had its successes, offering encouragement for future applications in clinical
      practice.

PMID- 9240967
TI  - The potential for isoenzyme-selective modulation of protein kinase C.
AB  - Protein kinase C (PKC) is a phospholipid-dependent serine/threonine kinase family
      consisting of at least 11 closely related isoenzymes. The different PKC
      isoenzymes play important roles in signal transduction pathways. The exact
      significance of each isoenzyme is not known at present; therefore, the
      elucidation of the roles of the various PKC isoenzymes is important. To explain
      the function of distinct PKC isoenzymes, the availability of isoenzyme-specific
      inhibibitors or activators would be an advantage. PKC inhibitors have been known
      for some time, but these compounds are not isoenzyme-specific and also inhibit
      other kinases. Recently, an inhibitor selective for PKC alpha and another one
      selective for PKCbetaI and betaII were described. Both compounds compete with the
      ATP binding sites that exhibit high homologies among the different PKC
      isoenzymes. Among others, the phosporyl transfer region, the pseudosubstrate
      domain, the phorbolester binding sequences, and the phosphorylation sites may
      also be targets for modulation of isoenzyme-specific PKC activity. The question
      is whether the differences in these domains and the substrate specificity of the
      PKC isoenzymes will allow isoenzyme-specific inhibition. In this review the human
      sequences of these sites, isoenzyme-specific substrates, inhibitory compounds,
      and inhibitory peptides are summarized.

PMID- 9240968
TI  - Regulation of membrane stability and the acrosome reaction in mammalian sperm.
AB  - Membrane destabilization is an essential step in the process of membrane fusion.
      In many cell types, exocytotic fusion may occur sporadically at microscopically
      localized sites on the surface of the cell, making it difficult to study the
      chemical and physical features of the membrane (or membranes) that promote
      fusion. In the sperm cell, exocytosis occurs synchronously at a distinct region
      on the sperm head. This localization of function makes the sperm cell a useful
      model to investigate the structural features of the bilayers that control
      membrane fusion. During sperm maturation, the anterior head membranes undergo a
      well-defined series of chemical, physical, and functional changes that are
      necessary to produce a fertile gamete. These changes include the addition of
      highly unsaturated phosphatidylcholine, a decrease in general membrane stability,
      and an increase in the ability to respond to physiological and pharmacological
      inducers of exocytosis. Concomitant addition of cholesterol and an actively
      maintained asymmetric transmembrane phospholipid distribution modulate these
      effects to stabilize the membrane of the mature sperm for storage. The
      environment of the female tract provides conditions that promote efflux of
      cholesterol from the sperm plasma membrane as well as the loss of membrane
      asymmetry. The cholesterol-poor, lipid-symmetric plasma membrane has a
      destabilized inner leaflet that facilitates membrane fusion upon binding of the
      sperm to the appropriate egg coat receptors. We summarize these features in a
      mechanistic model in which the sperm membrane contains destabilizing components
      to confer fusogenic potential as well as stabilizing components organized to
      maximize membrane integrity. This combination prevents premature fusion in the
      male tract. After deposition in the female tract and removal of the stabilizing
      components, followed by reorganization of the fusogenic components, the membrane
      becomes poised to fuse upon receipt of the final biological stimulus.

PMID- 9240969
TI  - Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen
      matrix: a new heart muscle model system.
AB  - A method has been developed for culturing cardiac myocytes in a collagen matrix
      to produce a coherently contracting 3-dimensional model heart tissue that allows
      direct measurement of isometric contractile force. Embryonic chick cardiomyocytes
      were mixed with collagen solution and allowed to gel between two Velcro-coated
      glass tubes. During culture, the cardiomyocytes formed spontaneously beating
      cardiac myocyte-populated matrices (CMPMs) anchored at opposite ends to the
      Velcro-covered tubes through which they could be attached to a force measuring
      system. Immunohistochemistry and electron microscopy revealed a highly organized
      tissue-like structure of alpha-actin and alpha-tropomyosin-positive cardiac
      myocytes exhibiting typical cross-striation, sarcomeric myofilaments,
      intercalated discs, desmosomes, and tight junctions. Force measurements of paced
      or unpaced CMPMs were performed in organ baths after 6-11 days of cultivation and
      were stable for up to 24 h. Force increased with frequency between 0.8 and 2.0 Hz
      (positive "staircase"), increasing rest length (Starling mechanism), and
      increasing extracellular calcium. The utility of this system as a test bed for
      genetic manipulation was demonstrated by infecting the CMPMs with a recombinant
      beta-galactosidase-carrying adenovirus. Transduction efficiency increased from
      about 5% (MOI 0.1) to about 50% (MOI 100). CMPMs display more physiological
      characteristics of intact heart tissue than monolayer cultures. This approach,
      simpler and faster than generation of transgenic animals, should allow functional
      consequences of genetic or pharmacological manipulation of cardiomyocytes in
      vitro to be studied under highly controlled conditions.

PMID- 9240970
TI  - Serine protease inhibitors block neutral sphingomyelinase activation, ceramide
      generation, and apoptosis triggered by daunorubicin.
AB  - To address the role of a plausible protease cascade in daunorubicin-triggered
      apoptosis, we evaluated the effect of cell-permeant protease inhibitors on its
      signal transduction pathway. Treatment of U937 and HL-60 cells with 0.5-1 microM
      of the chemotherapeutic drug daunorubicin induced a greater than 30% activation
      of neutral sphingomyelinase activity within 4-10 min with concomitant
      sphingomyelin hydrolysis and ceramide generation. DNA fragmentation and the
      classical morphological features of apoptosis were observed within 4-6 h.
      Pretreatment of cells with the serine protease inhibitors N-tosyl-L-phenylalanyl
      chloromethyl ketone (20 microM) or dichloroisocoumarin (20 microM) for 30 min
      inhibited daunorubicin-induced neutral sphingomyelinase activation, sphingomyelin
      hydrolysis, ceramide generation, and apoptosis. Other cell-permeant protease
      inhibitors such as pepstatin, leupeptin, and antipain had no such effect. The
      apoptotic response could be restored by the addition of 25 microM cell-permeant
      C6-ceramide. Daunorubicin-induced NF-kappaB activation was inhibited by
      dichloroisocoumarin but not by N-tosyl-L-phenylalanyl chloromethyl ketone,
      suggesting that this transcription factor can be activated independently of
      ceramide and is not directly implicated in the apoptotic pathway. These results
      suggest that inhibitors of serine proteases can act upstream of ceramide in drug
      triggered apoptosis and that neutral sphingomyelinase activation is either
      directly or indirectly serine protease dependent.

PMID- 9240971
TI  - Homocysteine signal cascade: production of phospholipids, activation of protein
      kinase C, and the induction of c-fos and c-myb in smooth muscle cells.
AB  - Hyperhomocysteinemia has been recognized as an independent risk factor for
      cerebral, coronary, and peripheral atherosclerosis. To examine the contribution
      of homocysteine (H[cys]) in the pathogenesis of vascular diseases, we sought to
      determine whether the H[cys] effect on vascular smooth muscle (VSMC)
      proliferation is mediated by a specific receptor/transporter or is due to an
      interaction with growth factors or cytokines. We show that H[cys] induced c-fos
      and c-myb and increased DNA synthesis and cell proliferation 12-fold in neural
      crest-derived VSMC (N-VSMC). The H[cys] effect on N-VSMC proliferation is
      inhibited by Mk-801, a noncompetitive antagonist of the N-methyl-D-aspartate
      (NMDA) receptor, a glutamate-gated calcium ion channel receptor, and CGS 19755, a
      competitive antagonist of NMDA-type glutamate receptor. H[cys] stimulates the
      synthesis of mass amounts of sn-1,2 diacylglycerol, and activates protein kinase
      C translocation from the nucleus and cytoplasm to cell membranes. Furthermore,
      protein kinase C inhibitors block the growth effect mediated by H[cys]. These
      findings indicate that H[cys]-mediated responses are coupled to diacylglycerol
      dependent protein kinase C activation. Our results suggest that homocysteine
      activates a receptor/transporter-like factor in neural crest derived smooth
      muscle.

PMID- 9240972
TI  - Assumptions.

PMID- 9240973
TI  - Biomechanics of ankle ligament reconstruction. An in vitro comparison of the
      Brostrom repair, Watson-Jones reconstruction, and a new anatomic reconstruction
      technique.
AB  - We wanted to use biomechanical testing in a cadaveric model to compare the
      Brostrom repair, the Watson-Jones reconstruction, and a new anatomic
      reconstruction method. Eight specimens were held in a specially designed testing
      apparatus in which the ankle position (dorsiflexion-plantar flexion and
      supination-pronation) could be varied in a controlled manner. Testing was done
      with intact ligaments and was repeated after sectioning of the anterior
      talofibular ligament and the calcaneofibular ligament and after a Brostrom
      repair, a Watson-Jones reconstruction, and a new anatomic reconstruction were
      performed. An anterior drawer test was performed using an anterior translating
      force of 10 to 50 N, and a talar tilt test was performed using a supination
      torque of 1.1 to 3.4 N-m. The forces in the anterior talofibular ligament and
      calcaneofibular ligament were measured with buckle transducers, and tibiotalar
      motion and total ankle joint motion were measured with an instrumented spatial
      linkage. The increase in ankle joint laxity observed after sectioning of both the
      anterior talofibular and calcaneofibular ligaments was significantly reduced by
      the three reconstructive techniques, although not always to the level of the
      intact ankle. Joint motion was restricted after the Watson-Jones procedure
      compared with that in the intact ankle. Unlike the Watson-Jones procedure, the
      ligament or graft force patterns observed during loading after the Brostrom
      repair and the new anatomic technique resembled those observed in the intact
      ankle.

PMID- 9240974
TI  - Injuries to the posterolateral aspect of the knee. Association of anatomic injury
      patterns with clinical instability.
AB  - Seventy-one consecutive patients with posterolateral knee injuries had clinical
      stability testing abnormalities documented prospectively. We compared these
      findings with the incidence and patterns of their injuries documented at surgery.
      An abnormal reverse pivot shift test was associated with injury to the fibular
      collateral ligament (P = 0.01), popliteal components (P = 0.01), and midthird
      lateral capsular ligament (P = 0.02). An abnormal posterolateral external
      rotation test at 30 degrees of flexion was associated with injury to the fibular
      collateral ligament (P = 0.0001) and lateral gastrocnemius tendon (P = 0.01). An
      abnormal adduction test at 30 degrees of flexion was associated with injury to
      the posterior arcuate ligament (P = 0.02). The results of this study should alert
      the clinician to the possibility of injury to a specific anatomic structure when
      the corresponding clinical stability test is abnormal. Because the fibular
      collateral ligament was injured in only 23% of the knees in this large series of
      patients, we recommend that an injury to the fibular collateral ligament not be
      the sole determining factor in making the diagnosis of posterolateral injuries.
      The wide array of injuries to many individual anatomic components that we found
      indicates the complexity of injuries to the posterolateral aspect of the knee.

PMID- 9240975
TI  - The fibular collateral ligament-biceps femoris bursa. An anatomic study.
AB  - The anatomy of the fibular collateral ligament-biceps femoris bursa is described.
      The bursa is located lateral to the distal quarter of the fibular collateral
      ligament and forms an inverted "J" shape around the anterior and anteromedial
      portions of the ligament. Its most distal margin is just proximal to the fibular
      head where the fibular collateral ligament inserts, and its more proximal aspect
      is at the superior edge of the anterior arm of the long head of the biceps
      femoris muscle. We found this structure in all 50 knees dissected; there was a
      constant anatomic location of the fibular collateral ligament-biceps femoris
      bursa in all specimens. Measurement of the anatomic dimensions of the bursa
      revealed a mean width of 8.4 mm and a mean height of 18 mm. Knowing the
      prevalence, shape, size, and anatomic location of this bursa may aid the
      clinician in the differential diagnosis of lateral knee pain.

PMID- 9240976
TI  - Magnetic resonance imaging for the evaluation of acute posterolateral complex
      injuries of the knee.
AB  - Clinical evaluation of posterolateral complex injuries of the knee can be
      difficult. To determine if magnetic resonance imaging can assist in decision
      making in the treatment of posterolateral complex injuries, six consecutive
      patients with acute posterolateral knee trauma were imaged preoperatively with
      standard magnetic resonance imaging sequences. Magnetic resonance imaging
      findings were then correlated with results of examination under anesthesia or
      open lateral reconstruction. There were five complete lateral complex injuries
      (grade III) and one partial tear. Magnetic resonance imaging was able to
      accurately depict the extent of injury preoperatively in each case. All patients
      had concomitant anterior cruciate ligament tears. There was one partial posterior
      cruciate ligament tear. Visualization of the arcuate complex, biceps femoris
      tendon, lateral capsule, iliotibial band, popliteal tendon, and lateral
      collateral ligament was possible. A characteristic bone contusion on the
      anteromedial femoral condyle was present in all patients with complete
      posterolateral disruptions. Lateral complex injuries of the knee can be very
      accurately demonstrated on magnetic resonance imaging, and this imaging technique
      can be used to clarify the exact nature of the injury to allow better surgical
      planning.

PMID- 9240977
TI  - In vitro evaluation of shoulder external rotation after a Bankart reconstruction.
AB  - The Bankart procedure is a commonly performed anterior shoulder reconstruction
      that may shorten the anterior capsule. In this study, biomechanical testing was
      performed to evaluate the effect of the classic Bankart reconstruction on
      external rotation of the shoulder. The procedure was performed on six fresh
      frozen cadaveric specimens that were free of intraarticular pathologic changes.
      With the arm in 0 degrees of abduction, resisting torques about the vertical axis
      were measured while the humerus was externally rotated. The intact specimens
      demonstrated a nonlinear load displacement behavior in which little resisting
      torque was measured until a moderate amount of external rotation was applied.
      Shortening the capsule by 2 mm resulted in a 40% decrease in the low-tension zone
      of external rotation, and shortening the capsule an additional 5 mm resulted in a
      67% decrease in the low-tension zone. This study demonstrates that the normal
      shoulder capsule is quite sensitive to anterior capsular shortening and suggests
      that care must be exercised when performing a Bankart reconstruction to avoid
      overtightening this structure.

PMID- 9240978
TI  - Shoulder strength and range of motion in symptomatic and pain-free elite
      swimmers.
AB  - To evaluate differences in shoulder strength and range of motion between painful
      and pain-free shoulders we examined two matched groups of athletes. Fifteen
      competitive swimmers were allocated to two groups. Group 1 consisted of seven
      swimmers with unilateral shoulder pain related to swimming (Neer and Welsh phase
      I to II). The control group (Group 2) consisted of eight swimmers with no present
      or previous history of shoulder pain. Concentric and eccentric internal
      rotational torques were reduced in painful shoulders in between-group comparisons
      as well as in side-to-side comparisons. The decrease in internal rotational
      torque resulted in significantly greater concentric and eccentric external-to
      internal rotational strength ratios of the painful shoulder in Group 1 swimmers
      compared with the controls. Furthermore, the functional ratio (eccentric external
      rotation:concentric internal rotation) was significantly greater in the painful
      shoulder in both between-group and side-to-side comparisons. Both groups of
      swimmers exhibited increased external range of motion and reduced internal range
      of motion compared with normalized data, but no between-group or side-to-side
      differences were detected. Our findings suggest that prevention or rehabilitation
      of swimmer's shoulder might not solely involve strengthening of the external
      rotators of the shoulder joint. Attention might also be drawn toward correction
      of a possible deficit in internal rotational strength. Changes in shoulder range
      of motion seem unrelated to the occurrence of shoulder pain.

PMID- 9240979
TI  - A comparison of results in acute and chronic anterior cruciate ligament ruptures
      of arthroscopically assisted autogenous patellar tendon reconstruction.
AB  - We conducted a prospective study of 94 consecutive patients who received a
      patellar tendon autograft for anterior cruciate ligament rupture. Eighty-seven
      patients (93%) returned for followup a mean of 28 months postoperatively; 57 had
      chronic and 30 had acute or subacute ruptures. There were no significant
      differences between the subgroups for age, sex, articular cartilage lesions, or
      months of followup. Forty-six meniscal tears were repaired; 27 of these extended
      into the central avascular region. Rehabilitation emphasized immediate knee
      motion, but strenuous activity was delayed for at least 4 months. Only one
      patient had a knee motion complication, and stability (<3 mm, KT-2000
      arthrometer, 134 N) was restored in 85% of knees with chronic ruptures and 92% of
      knees with acute ruptures. Earlier reconstruction should be considered in active
      persons as symptoms and limitations continued postoperatively in knees with
      chronic ruptures, leading to overall less satisfactory results. In patient rating
      of the overall knee condition, 69% of knees with chronic ruptures and 100% of
      knees with acute ruptures scored in the normal or very good range. Repair of
      meniscal tears that extend into the central avascular region should be
      considered, as 24 of the 27 (89%) menisci repaired showed clinical evidence of
      healing and did not require reoperation.

PMID- 9240980
TI  - Anterior cruciate ligament graft fixation. Initial comparison of patellar tendon
      and semitendinosus autografts in young fresh cadavers.
AB  - The initial biomechanical properties of semitendinosus and patellar tendon
      autografts and their fixation strengths were investigated. Twenty fresh cadaveric
      knees from donors under 42 years of age were used in the study. After removing
      all soft tissues other than the anterior cruciate ligament, we determined the
      ultimate tensile strength (2195 +/- 427 N) and stiffness (306 +/- 80 N/mm) of the
      anterior cruciate ligament in nine knees. In six knees, anterior cruciate
      ligaments were reconstructed using an autologous patellar tendon graft with
      proximal and distal interference fit screws; this resulted in an ultimate tensile
      strength of 416 +/- 66 N. Five knees were reconstructed with quadruple-stranded
      (double-looped) semitendinosus tendons fixed proximally by a titanium button and
      braided tape and distally by tibial post screw. This resulted in an ultimate
      tensile strength of 612 +/- 73 N, which was significantly higher than the
      strength in the patellar tendon group. Graft stiffness did not differ between the
      groups and was 47 +/- 19 N/mm (N = 11). This study demonstrates that the
      reconstructed knees had only 20% to 30% of the ultimate tensile strength of the
      normal anterior cruciate ligament. In summary, the semitendinosus reconstruction
      using a button for proximal fixation is, at the time of surgery, approximately
      50% stronger than patellar tendon reconstructions with similar stiffness.

PMID- 9240981
TI  - Intratester and intertester reliability of the KT-1000 arthrometer in the
      assessment of posterior laxity of the knee.
AB  - We measured tibial translation in the knees of 22 subjects with posterior
      cruciate ligament tears or reconstructions by using the KT-1000 arthrometer. To
      assess the reliability of the device, two testers made measurements. One tester
      was a novice and the second tester had substantial clinical experience with the
      KT-1000 arthrometer. The quadriceps neutral angle was found for the uninvolved
      knee. Anterior and posterior translation and total anterior-posterior excursion
      were then measured. The quadriceps neutral angle was then reproduced in the
      involved knee and the same measurements were taken. Each subject was tested twice
      by each tester. The intraclass correlation coefficient values for the novice,
      experienced, and intertester reliability were 0.67, 0.79, and 0.62, respectively,
      for corrected posterior translation; 0.59, 0.68, and 0.64, respectively, for
      corrected anterior translation; 0.70, 0.74, and 0.29, respectively, for
      quadriceps neutral angle; and 0.84, 0.83, and 0.62, respectively, for total
      anterior-posterior excursion. Ninety-five percent confidence intervals for the
      novice, experienced, and intertester reliability were +/-2.95, +/-2.53, and +/
      3.27 mm, respectively, for corrected posterior translation; +/-3.99, +/-3.89, and
      +/-3.74 mm, respectively, for corrected anterior translation; and +/-10.70
      degrees, +/-11.73 degrees, and +/-16.25 degrees, respectively, for quadriceps
      neutral angle. The KT-1000 arthrometer was found to be a moderately reliable tool
      for the measurement of tibial translation in patients with posterior cruciate
      ligament tears and reconstructions.

PMID- 9240982
TI  - Concomitant meniscal and articular cartilage lesions in the femorotibial joint.
AB  - The frequency of concomitant meniscal and articular cartilage lesions in the
      femorotibial joint was analyzed in a retrospective study of 1740 knee joints
      examined arthroscopically with the objective of determining possible correlations
      between the two knee joint abnormalities. Articular cartilage lesions were found
      in 81.4% (N = 1416) of femorotibial joints examined and meniscal derangements
      were noted in 72.8% (N = 1268). In the medial compartment, concomitance was noted
      in 76.3% (821 of 1076) on the femoral condyles and in 48.6% (523 of 1076) on the
      tibial plateau. In the lateral compartment, 43.1% (212 of 492) of the knees with
      deranged menisci had femoral and 55.1% (271 of 492) had tibial articular lesions.
      Medial meniscal lesions were more frequently associated with femoral and tibial
      chondral degeneration than lateral meniscal derangements (P < 0.001).
      Longitudinal, bucket-handle, and complex tears of the medial meniscus were
      significantly more often associated with articular cartilage damage than
      horizontal cleavage, flap, or radial tears. Degeneration of the meniscus was
      highly correlated with chondral destruction in both compartments. No cause-and
      effect relationship could be established, but practical implications of these
      findings are discussed.

PMID- 9240984
TI  - Predictors of injury in ice hockey players. A multivariate, multidisciplinary
      approach.
AB  - Eighty-six male high school ice hockey players participated in this prospective
      study to determine both the incidence of injury in high school ice hockey and the
      influence of physical, situational, and psychosocial factors. Physical factors
      included height, weight, vision, previous injuries, musculoskeletal
      abnormalities, and injuries present at the time of screening evaluations.
      Situational factors examined were level of participation, playing time, player
      position, and games versus practices. Psychosocial factors such as confidence,
      stress, social support, positive states of mind, and mood states were also
      examined to determine their influences on injury. Twenty-seven injuries occurred
      during the 1994 to 1995 season. As hypothesized, the overall incidence of injury
      in high school hockey games (34.4 per 1000 player-game hours) was less than the
      incidence of injury in Junior A hockey (96.1 per 1000 player-game hours) and was
      more than previously reported for Bantam youth hockey (10.9 per 1000 player-game
      hours). Injuries occurred more often in games than in practices, usually as a
      result of collisions. Physical factors such as player position and previous
      injuries did not significantly predict injuries, but players in the high playing
      time group were more likely to be injured. Psychosocial factors of low vigor and
      high fatigue as measured by the Incredibly Short Profile of Mood States (ISPOMS)
      significantly predicted high school ice hockey injuries.

PMID- 9240983
TI  - Ice hockey injuries in Finland. A prospective epidemiologic study.
AB  - In this prospective study of ice hockey injuries in Finland we have investigated
      the incidence of injury at two playing levels and the causal factors, mechanisms,
      types, and consequences of the injuries. Seven Finnish ice hockey teams were
      observed during the 1988 to 1989 season. There were a total of 189 injuries.
      There were 134 injuries in 4 teams of the highest level, the Finnish National
      League, and 55 injuries in 3 teams of the second highest level, Division I. The
      incidence of injuries during games was 66 per 1000 player-game hours in the
      National League and 36 per 1000 player-game hours in Division I. As for severity,
      10 (5%) injuries were classified as major. Of all injuries, 15 (8%) were
      fractures and 34 (18%) were to the head or face. The most severe injuries were
      tears of a knee ligament or fractures of an upper extremity. Ongoing surveillance
      and an exact reporting system are needed for establishing the trends in the
      number and severity of the injuries.

PMID- 9240985
TI  - Injuries in the sport of luge. Epidemiology and analysis.
AB  - We undertook this study to determine the types and frequency of injuries
      sustained in the sport of luge. Before this study, no data were available in the
      medical literature on luge injuries. We performed a retrospective analysis
      between the years 1985 and 1992 using data obtained from the athlete injury and
      illness report forms at the US Training Center Sports Medicine Clinic in Lake
      Placid, New York. During the 7 years examined, 1043 athletes took 57,244 track
      runs and sustained 407 injuries. The risk of sustaining an injury was 0.39 per
      person per year, and the risk of an injury causing the loss of more than 1 day of
      practice was 0.04 per person per year. Contusions were the major injury (51%),
      followed by strains (27%). Strains of the neck muscles and contusions of
      extremities, especially the hands, were characteristic injuries sustained by
      athletes. The most serious injuries were concussions (2%) and fractures (3%).
      Crashes were responsible for 64% of injuries. Luge appears to be a relatively
      safe sport with injury rates comparable with recreational alpine skiing.

PMID- 9240986
TI  - A rigorous comparison between the sexes of results and complications after
      anterior cruciate ligament reconstruction.
AB  - Although there is a higher relative incidence of anterior cruciate ligament
      injuries in female than in comparable male athletes according to the literature,
      the majority of populations studied after reconstruction are male-dominated. We
      wished to determine whether a selection bias for reconstruction based on sex is
      warranted according to complications and outcome. Ninety-four patients (47 of
      each sex) were matched for chronicity of injury, age, preoperative sports
      activity levels, articular cartilage condition, and months of followup. All had
      patellar tendon autogenous reconstruction and a similar program of immediate knee
      motion and early return to function. The results were rated with the Cincinnati
      Knee Rating System. At a mean of 26 months postoperatively, there were no
      significant differences for complications or outcome between men and women. Women
      required an average of six more rehabilitation visits than men; however, none
      required additional surgery for knee motion complications and the rate of
      patellofemoral crepitus conversion was only 7%, lower than that found for men
      (15%). The overall failure rate was low, only 6% for women and 4% for men. We
      concluded that the functional rehabilitation program was effective, postoperative
      complications were few, and no scientific basis exists to use sex alone as a
      selection criteria for anterior cruciate ligament reconstruction.

PMID- 9240987
TI  - An analysis of anterior cruciate ligament reconstruction in middle-aged patients.
AB  - The purpose of this study was to evaluate the results and complications of
      anterior cruciate ligament surgery in middle-aged patients. Forty-five
      consecutive patients over 40 years old (average age, 44.6 years) who had
      arthroscopically assisted anterior cruciate ligament reconstructions with
      midthird patellar tendon autografts were evaluated. The patients returned for
      interviews, physical examinations, radiographs, Biodex dynamometer strength
      testing, and KT-1000 arthrometer testing at an average of 37 months after their
      surgeries (range, 24 to 96 months). The mean Lysholm and Gillquist score was 91,
      which corresponds to symptoms only with vigorous activity. The overall scores
      from the International Knee Documentation Committee form were 29 (64%) normal or
      nearly normal and 2 (4%) severely abnormal. Side-to-side differences as
      determined by the KT-1000 arthrometer were < or = 3 mm in 31 of 40 patients
      (78%), between 3 and 5 mm in 4 patients (10%), and > 5 mm in 5 patients at 30
      pounds of anterior displacement. Seventy-six percent of the patients (N = 34)
      returned to their preoperative activity levels. Three patients required repeat
      arthroscopic surgery for persistent knee pain and two patients had graft
      ruptures. This study shows that when middle-aged patients undergo surgery, their
      results can be successful and satisfying to a degree similar to those of younger
      patients.

PMID- 9240988
TI  - Correlation of patellar articular lesions with results from anteromedial tibial
      tubercle transfer.
AB  - This retrospective study determined that the outcome from anteromedialization of
      the tibial tubercle correlates well with the location of patellar articular
      lesions. Detailed descriptions of patellar articular cartilage lesions were
      obtained from the operative reports of 36 patients who had anteromedialization
      performed between February 1984 and March 1994. The patterns fell into four
      distinct groups. Ten patients with type I (distal) patellar lesions and 13
      patients with type II (lateral facet) patellar lesions had 87% good to excellent
      subjective results, and 100% of these patients said they would have the procedure
      done again. Nine patients with type III (medial facet) lesions had 55% good to
      excellent results, and 5 patients with type IV (proximal or diffuse) lesions had
      only 20% good to excellent results. Patients with type I or II lesions were
      significantly more likely to have good or excellent results than those with type
      III or IV lesions. Central trochlear lesions were associated with medial patellar
      lesions and all patients with central trochlear lesions had poor results. There
      was no significant correlation between the Outerbridge grading of the patellar
      lesion and the overall results. Workers' compensation issues diminished the
      likelihood of a satisfactory outcome by 19%; however, this was not statistically
      significant. This is the first study to correlate the patellar articular
      cartilage lesion with outcome after tibial tubercle transfer.

PMID- 9240989
TI  - Ankle disk training influences reaction times of selected muscles in a simulated
      ankle sprain.
AB  - Ankle disk training has been used as an exercise in sports medicine clinics to
      help protect against ankle sprains. This study investigated the effects of ankle
      disk training on the contraction pattern of the anterior tibialis, posterior
      tibialis, peroneus longus, and flexor digitorum longus muscles in a simulated
      ankle sprain. Twenty adults were recruited and divided into a control group and
      an experimental group. A platform with a trapdoor was used to simulate a lateral
      ankle sprain. Electromyographic data were recorded from each subject in
      pretraining and posttraining tests. The experimental group underwent ankle disk
      training for 8 weeks between the pretraining and posttraining tests. In the
      pretraining test, the four muscles started to contract simultaneously; in the
      posttraining test, the contractions of the anterior and posterior tibialis
      muscles were delayed. This delay favors the correction of excessive ankle
      inversion. This study examined the effects of one form of proprioceptive training
      on muscle reaction times, and its results may explain why such training can help
      protect against ankle sprains.

PMID- 9240991
TI  - Analysis of a semitendinosus autograft in a rabbit model.
AB  - The purpose of this study was to evaluate the histologic and biomechanical
      changes that occur between 12 and 52 weeks in an intraarticular, semitendinosus
      autograft placed through tibial and femoral drill holes in a rabbit model. The
      results of this study show that, in this rabbit model, the soft tissue graft
      maintained its biologic fixation in the osseous tunnel when stressed to failure
      at 1 year. The bony fixation occurred by the formation of an indirect tendon
      insertion, and this formation was complete by 26 weeks. At 52 weeks, large
      differences persisted in the strength and stiffness of the graft compared with
      the normal semitendinosus tendon and anterior cruciate ligament. Based on the
      results of this study, we support a cautious approach in returning patients to
      early full activity, including sports, after anterior cruciate ligament
      reconstruction with a semitendinosus autograft.

PMID- 9240990
TI  - A randomized controlled trial of piroxicam in the management of acute ankle
      sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study.
AB  - Three hundred sixty-four Australian Regular Army recruits with acute ankle
      sprains sustained during training were randomized to treatment with either
      piroxicam or placebo. Compared with the placebo group, subjects treated with
      piroxicam had less pain, were able to resume training more rapidly, were treated
      at lower cost, and were found to have increased exercise endurance on resumption
      of activity. Nausea was the only side effect reported significantly more often in
      the treatment group than in the placebo group (6.8% versus 0.3%). Interestingly,
      subjects treated with piroxicam showed some evidence of local abnormalities such
      as instability and reduced range of movement. We conclude that nonsteroidal
      antiinflammatory agents should form an integral part of the treatment of acute
      ankle sprains.

PMID- 9240992
TI  - Matrix assessment of the articular cartilage surface after chondroplasty with the
      holmium:YAG laser.
AB  - The goal of this study was to evaluate, histologically and biochemically, repair
      of the articular cartilage in a rabbit joint after the use of the holmium:yttrium
      aluminum-garnet laser in a cartilage chondroplasty model. In 30 New Zealand White
      rabbits, chondroplasty was performed with the laser at an intensity of 0.8 J at a
      rate of 10 Hz. The animals were sacrificed 12 weeks after surgery.
      Histologically, the safranin O staining index of proteoglycan correlated well
      with the biochemical results, illustrating a decrease of proteoglycan in the
      repaired articular cartilage after laser articular cartilage chondroplasty. The
      damaged articular cartilage surface after the laser application was extensive.
      The damaged area observed was gradually distributed along the radius from the
      central point of the laser beam application. Biochemically, the amount of
      glycosaminoglycan in the repaired tissue (8 +/- 2 mg of hexosamine per gram of
      dry cartilage) was statistically less when compared with that in the sham-treated
      tissue (40 +/- 5 mg). The amount of sulfate incorporated into proteoglycans was 8
      to 10 times less in the chondroplasty model compared with the control, suggesting
      that cell viability was greatly reduced in the treated tissues or expression of
      proteoglycans was greatly reduced. In the subchondral area, histologic evaluation
      showed the lack of osteocytes in lacunae of the bone tissue after use of laser
      energy. The architecture of the subchondral bone in the chondroplasty area was
      damaged, with damage also seen in the membranes of the blood vessels.

PMID- 9240993
TI  - Fracture of the proximal tibia with immediate weightbearing after a Fulkerson
      osteotomy.
AB  - The records of 234 people who had anteromedialization of the tibial tubercle with
      oblique osteotomy between 1983 and 1994 at two separate institutions were
      reviewed retrospectively. Six patients (2.6%) had fractures of the proximal tibia
      postoperatively, within 13 weeks of the Fulkerson osteotomy. All fractures
      occurred after a change in the postoperative physical therapy regimen from
      partial weightbearing to immediate full weightbearing. All fractures healed with
      acceptable alignment of less than 5 degrees of varus-valgus or anteroposterior
      angulation. Given this increase in fracture incidence, a more conservative
      postoperative physical therapy regimen is recommended. All patients should be
      nonweightbearing initially, advanced gradually to partial weightbearing, and
      allowed full weightbearing only after the osteotomy has radiographic evidence of
      complete healing.

PMID- 9240994
TI  - The biomechanics of the human in flight.
AB  - I used a computer simulation model of aerial movement to investigate the
      techniques for producing and controlling rotations of the human body during free
      flight. I found that the rotational motion can change from a twisting somersault
      to a nontwisting somersault by flexing at the hips at a suitable time. Twist may
      be produced in the aerial phase by means of asymmetrical movements of arms or
      hips, which result in a tilting of the longitudinal axis away from the plane
      perpendicular to the angular momentum vector. Asymmetrical movements may also
      remove the tilt and stop the twist. Elite performances of twisting somersaults
      are characterized by a large contribution from aerial twisting techniques. A
      progression of movements is presented for learning a double somersault with one
      and a half twists in the second somersault.

PMID- 9240995
TI  - Lower extremity arterial disease in sports.
AB  - The recent description of exercise-induced intimal fibrosis affecting mainly the
      iliac artery (and therefore usually described as external iliac artery
      endofibrosis) has dramatically changed the diagnostic approach of unexplained
      recurrent lower limb exercise pain, especially in cyclists. Because arterial
      disease is often associated with the aftereffect of various concomitant
      musculotendinous lesions, several months may pass before an arterial origin is
      suspected. The arterial origin of the pain must not be eliminated on normal ankle
      to-arm index or normal Doppler velocity profiles at rest. Ultrasound examinations
      taken at rest may show the lesions in 80% of endofibrotic patients and allow for
      the diagnosis of popliteal entrapment syndrome during dorsiflexion of the foot.
      However, the hemodynamic consequences of a stenosis on the aortoiliofemoral axis
      can only be proved by measurement of the ankle-to-arm index after exercise. A
      cutoff of this index <0.5 provides an 85% sensitivity in the detection of
      endofibrosis. Invasive investigations (arteriography or angioscopy) will confirm
      the diagnosis before surgery is discussed. Although long-term results in
      endofibrosis are unknown, most of the surgically treated patients return to
      competition.

PMID- 9240996
TI  - A statistics primer. Statistical tests for discrete data.

PMID- 9240997
TI  - Traumatic peroneal tendon instability.

PMID- 9240998
TI  - Traumatic tears of the subscapularis tendon.

PMID- 9240999
TI  - The diagnosis of meniscal tears in athletes. A comparison of clinical and
      magnetic resonance imaging investigations.

PMID- 9241000
TI  - Compartment syndrome after arthroscopic surgery of the knee. A report of two
      cases managed nonoperatively.

PMID- 9241001
TI  - Fruit juices and pharmacology.

PMID- 9241003
TI  - Brofaromine for social phobia: a multicenter, placebo-controlled, double-blind
      study.
AB  - The safety and efficacy of brofaromine, a reversible and selective monoamine
      oxidase inhibitor, were examined in a multicenter trial of 102 outpatients with
      social phobia. After a 1-week placebo washout, subjects were randomly assigned to
      10 weeks of treatment with either brofaromine (N = 52) or placebo (N = 50).
      Brofaromine dosage began at 50 mg/day and was titrated to a maximum of 150
      mg/day, depending on treatment response. Brofaromine produced a significantly
      greater change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores
      compared with placebo, F(1) = 6.01, p < 0.016. Mean LSAS scores decreased from
      81.8 at baseline to 62.6 at endpoint for brofaromine, t = 5.41,p < 0.001, and
      from 79.8 to 70.7 for placebo, t = 3.66, p < 0.001. Eleven of the 14 brofaromine
      early terminators discontinued because of adverse experiences, as did 4 of the 17
      placebo early terminators. Side effects more common with brofaromine than placebo
      included insomnia, dizziness, dry mouth, anorexia, tinnitus, and tremor. No
      clinically significant variations in vital signs or laboratory values were found.
      The findings are consistent with the clinical efficacy for the treatment of
      social phobia.

PMID- 9241002
TI  - Moclobemide in social phobia: a controlled dose-response trial.
AB  - Although the monoamine oxidase inhibitor phenelzine has proven efficacious in
      social phobia, the risk of hypertensive crises has reduced its acceptability. The
      reversible monoamine oxidase inhibitor moclobemide has less potential for such
      reactions, but its efficacy in this disorder remains unproven. A double-blind,
      placebo-controlled study was undertaken to assess the efficacy and safety of
      fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social
      phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300
      mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward
      greater efficacy of higher doses of moclobemide was observed at 8 weeks, no
      differences in response to various doses of the drug and placebo were observed at
      12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those
      on placebo were at least much improved. Moclobemide was well tolerated, insomnia
      being the only dose-related adverse event observed with the drug. In this dose
      response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other
      controlled studies have found moclobemide and brofaromine, another reversible
      monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for
      inconsistent findings are discussed.

PMID- 9241004
TI  - Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual
      dysphoric disorder.
AB  - Serotonergic antidepressants have been shown to be effective treatments for
      premenstrual dysphoric disorder (PMDD). The efficacy of nonserotonergic
      antidepressants is less well studied. This study was a two-center, parallel
      design, placebo-controlled, randomized trial of fluoxetine, bupropion, and
      placebo in women with PMDD. Thirty-four women with PMDD completed 1 month of
      single-blind placebo and 2 months of fluoxetine 20 mg/day (N = 10), bupropion 100
      mg three times daily (N = 12), or placebo (N = 12). Clinical Global Impressions
      (CGI) Scale, an expanded form of the Hamilton Rating Scale for Depression (HAM
      D), and Global Assessment Scale (GAS) ratings were obtained premenstrually in
      each of the three treatment cycles. The three treatment groups differed
      significantly in efficacy by CGI ratings. Fluoxetine was superior to both
      bupropion and placebo. Comparison of posttreatment to pretreatment HAM and GAS
      scores demonstrated significant superior efficacy of fluoxetine compared with
      placebo. Posttreatment HAM and GAS scores for bupropion were intermediate between
      but not significantly different from fluoxetine or placebo. In summary,
      fluoxetine was significantly superior to bupropion and placebo as an effective
      treatment for PMDD. Although some improvement with bupropion was noted, and both
      medications were well tolerated, patient satisfaction was far greater with
      fluoxetine.

PMID- 9241005
TI  - Efficacy of fluvoxamine, paroxetine, and citalopram in the treatment of obsessive
      compulsive disorder: a single-blind study.
AB  - Obsessive-compulsive disorder (OCD) has been successfully treated with
      proserotonergic agents for some years. Clomipramine was the first drug used, but
      several clinical trials have been conducted more recently to assess the
      antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). The
      aim of this study was to compare the antiobsessional efficacy of three SSRIs,
      fluvoxamine, paroxetine, and citalopram. Thirty obsessive-compulsive patients
      without comorbid axis I diagnoses except for tic disorder as assessed by DSM-III
      R criteria gave informed consent and were recruited consecutively; they underwent
      a 10-week randomized treatment with fluvoxamine, paroxetine, or citalopram.
      Ratings were performed under blind conditions every 2 weeks from baseline to the
      end of the study and by the Yale-Brown Obsessive-Compulsive Scale, the National
      Institute of Mental Health-Obsessive-Compulsive Scale, the Clinical Global
      Impressions Scale, and the Hamilton Rating Scale for Depression. Quantitative and
      qualitative analyses of the antiobsessional efficacy of the three drugs were
      completed with analysis of variance with repeated measures and survival analysis.
      The results showed no significant differences between the three treatments. The
      preliminary conclusions drawn from this study concern the interchangeable
      antiobsessional effects of different SSRIs, although further studies of "cross
      response" to these drugs are needed.

PMID- 9241006
TI  - Gepirone and diazepam in generalized anxiety disorder: a placebo-controlled
      trial.
AB  - This randomized, double-blind clinical trial involving 198 generalized anxiety
      disorder (GAD) patients was conducted to more clearly define gepirone's role for
      the treatment of anxiety in daily dosages of 10 to 45 mg compared with diazepam
      and placebo. A secondary goal was to test for possible discontinuation symptoms
      after abrupt discontinuation of therapy. After a 1-week washout period, patients
      were treated for 8 weeks and then abruptly shifted under single-blind conditions
      for 2 weeks on placebo. The highest attrition rate occurred with patients on
      gepirone (58%) and the lowest on diazepam (34%). Medication intake for week 4 was
      19.5 +/- 12.5 mg/day diazepam and 19.0 +/- 11.5 mg/day gepirone and was similar
      at week 8. The major adverse events were light-headedness, nausea, and insomnia
      for gepirone and drowsiness and fatigue for diazepam. Clinical improvement data
      showed gepirone's anxiolytic response to be delayed, being significant from
      placebo beginning at week 6, whereas diazepam caused significantly more relief
      than placebo from week 1 onward. Taper results showed that only diazepam, but not
      gepirone, caused a temporary worsening of anxiety symptoms or rebound.

PMID- 9241007
TI  - Fluvoxamine treatment of trichotillomania.
AB  - The present study examined the efficacy of fluvoxamine in the treatment of
      trichotillomania (TM) and coexistent clinical features. Twenty-one participants
      with a principal diagnosis of TM were given fluvoxamine in a 12-week open trial.
      For 13 patients who completed treatment, significant improvement was noted on
      only a few measures of hair pulling. End-state analyses for the entire group of
      participants, however, demonstrated significant improvement in measures of
      distress, duration, control, and resistance. Significant decreases over treatment
      were also found on measures of coexistent anxiety for both the completer and the
      entire participant groups; depressive symptoms improved for completers.
      Conclusions about the effectiveness of fluvoxamine for treatment of TM cannot be
      drawn, given the uncontrolled nature of the study; however, end-state analyses
      suggest the potential utility of fluvoxamine in a subset of patients with TM.

PMID- 9241008
TI  - Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in
      extensive metabolizers.
AB  - In vitro studies have shown that fluoxetine and paroxetine are more potent
      inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of
      desipramine when coadministered with the selective serotonin reuptake inhibitors
      (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers
      (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23
      days in each phase of the crossover study with a 7-day drug-free period between
      phases. In addition, subjects were randomly assigned to receive concomitant
      paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18
      through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days
      18 through 20). SSRI treatments were switched between phases. After 10 days of
      coadministration at the lower dose, mean desipramine maximum concentration in
      plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with
      paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean
      desipramine 24-hour area under the concentration-time curve (AUC[24]) increased
      from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x
      h/mL (+37%) with sertraline; and the mean desipramine trough value (C0) increased
      from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL
      (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold
      increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold
      increase in these parameters for sertraline occurred simultaneously with the
      desipramine concentration changes. Thus, when coadministered with 50 mg/day
      desipramine, sertraline had significantly less pharmacokinetic interaction than
      paroxetine with desipramine at the recommended starting dosages of 50 mg/day and
      20 mg/day, respectively.

PMID- 9241009
TI  - The effect of fluvoxamine on serum prolactin and serum sodium concentrations:
      relation to platelet 5-HT2A receptor status.
AB  - Hyperprolactinemia and hyponatremia are adverse drug reactions regularly reported
      for selective serotonin reuptake inhibitors. Results from animal studies suggest
      that serotonin receptors of different subtypes are involved in the mediation of
      these effects. We have investigated to what extent fluvoxamine alters serum
      prolactin and serum sodium levels and whether these effects are related to
      platelet 5-hydroxytryptamine 2A (5-HT2A) receptor status, as studied by
      [3H]lysergic acid diethylamide ([3H]LSD) binding. Eight healthy subjects were
      given fluvoxamine in increasing dosage from 25 mg/day to 200 mg/day during 4
      weeks, and serum sodium and serum prolactin concentrations were obtained weekly.
      All subjects had normal prolactin and sodium levels before start of treatment.
      Two subjects had substantial increases in serum prolactin levels (up to 35
      microg/L) during fluvoxamine treatment, and these two subjects had higher Bmax
      for platelet [3H]LSD binding before fluvoxamine treatment than the six other
      subjects (32.7 vs. 23.1 fmol/mg protein). There was a small, nonsignificant
      decrease (mean 1.0 mmol/L) in serum sodium levels after institution of
      fluvoxamine but a significant increase (mean 1.9 mmol/L) in serum sodium levels
      after discontinuation of the drug (p = 0.02). Bmax for [3H]LSD binding and change
      in serum sodium concentration after institution of fluvoxamine showed a
      significant positive correlation (r = 0.85;p = 0.007). The results indicate that
      fluvoxamine affects serum prolactin as well as serum sodium concentrations and
      lend indirect support to the suggestion that 5-HT2A receptors might be involved
      in the mediation of these effects.

PMID- 9241010
TI  - Economic and health state utility determinations for schizophrenic patients
      treated with risperidone or haloperidol.
AB  - The current study uses utility analysis to assess economic and quality-of-life
      benefits of risperidone in patients with chronic schizophrenia. A retrospective
      analysis was performed on Positive and Negative Syndrome Symptoms (PANSS) data
      obtained from the published Canadian multicenter risperidone trial (part of the
      North American trial). Cluster analysis applied to endpoint PANSS scores,
      including all patients (N = 135), identified three clusters representing 130
      patients with mild, moderate, and severe symptomatology. A narrative health state
      profile was written for each cluster, and 100 psychiatric nurses from Washington,
      DC, were asked to assign preference ratings to each one using linear analog and
      standard gamble (SG) methods. Mean utility values (confidence interval 95%)
      obtained from the SG ratings for the three health state profiles were 0.61 +/-
      0.069 (mild); 0.36 +/- 0.073 (moderate); and 0.29 +/- 0.071 (severe). The mild
      health state (including the majority of risperidone 6 mg-treated patients) was
      rated by nurses to have a 0.25 +/- 0.0501 greater utility than the moderate
      health state (composed of the majority of haloperidol-treated patients). The
      results of these utility evaluations (SG) by the nurses were related to the
      clinical outcome for three of the six drug treatment groups (N = 65) by
      multiplying the percentage of patients in each of the three clusters, both at
      baseline and end-point, who were receiving risperidone 6 mg/day, haloperidol, or
      placebo, by the utility value for the health state assigned to that cluster. The
      gain in utility for risperidone-treated patients was 2.6 times higher (0.125)
      compared with haloperidol-treated patients (0.049), and 7 times higher compared
      with placebo (-0.021). After multiplying the gain in utility of each treatment by
      the remaining expected life span for men and women, it was found that risperidone
      treated patients obtained more than twice as many quality-adjusted years as
      haloperidol patients. The incremental drug treatment cost divided by the
      incremental benefit of risperidone versus haloperidol was found to yield a
      favorable, generally accepted cost-utility ratio.

PMID- 9241011
TI  - Extrapyramidal signs and clinical symptoms in first-episode schizophrenia:
      response to low-dose risperidone.
AB  - The purpose of this study was to determine the prevalence of extrapyramidal signs
      or symptoms (EPS) and clinical symptoms in first-episode schizophrenia, before
      any treatment, during and after treatment with a novel antipsychotic,
      risperidone. Twenty-two (17 men; 5 women) patients were examined using the
      Extrapyramidal Symptom Rating Scale, Positive and Negative Syndrome Scale
      (PANSS), Clinical Global Impressions-Severity of Illness and Improvement, and
      Global Assessment of Functioning. Three patients (14%) had distinct EPS at
      baseline, whereas all were free of EPS after treatment with risperidone. On the
      maximum dose of risperidone (5-8 mg), 32% of the total sample developed mild
      akathisia or parkinsonism, both of which diminished with dosage reduction. No
      clinically significant EPS were observed in patients receiving 2 to 4 mg of
      risperidone. Analysis of symptom response of the lower (2-4 mg) versus the higher
      (5-8 mg) doses of risperidone resulted in superior outcome in the 2- to 4-mg
      group for all three symptom clusters of the PANSS. In addition, 91% of the low
      dose group achieved a 20% or greater reduction in total PANSS score compared with
      27% for the high-dose group. These findings have clinical relevance directed at
      the early and longer-term treatment of schizophrenia.

PMID- 9241012
TI  - Hepatotoxicity of clozapine.
AB  - Two hundred thirty-eight patients treated with either haloperidol or clozapine
      were investigated to shed more light on the incidence and severity of
      antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase
      (SGPT) increase was most frequently seen in both treatment groups. When analyzing
      the incidence rates for patients with increased liver enzyme values (serum
      glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were
      higher than twice the upper limit of the normal range, clozapine-treated patients
      showed an SGPT increase (37.3%) significantly more frequently than patients
      treated with haloperidol (16.6%). Both patients with higher clozapine plasma
      levels and male patients were at a higher risk for an SGPT increase. At least 60%
      of the increase of the different enzymes remitted within the first 13 weeks of
      treatment. In general, the authors conclude that clozapine-induced liver enzyme
      elevation seems to be a common and mostly transient phenomenon.

PMID- 9241014
TI  - Lack of interaction of monoamine oxidase inhibitors and epinephrine in an older
      patient.

PMID- 9241013
TI  - The effects of perphenazine on the concentration of nortriptyline and its
      hydroxymetabolites in older patients.
AB  - Twenty-five older patients who presented with psychotic depression were treated
      with a combination of nortriptyline and perphenazine. Plasma levels of
      nortriptyline, E-, and Z-10-OH nortriptyline (E- and Z-10-OH-NT) were measured
      before and after addition of perphenazine. The mean (+/-SD) initial nortriptyline
      dose was 59 +/- 24 mg/day, whereas the mean final nortriptyline and perphenazine
      doses were 56 +/- 24 and 19 +/- 13 mg/day, respectively. The mean plasma level to
      dose quotient for perphenazine (0.45 +/- 0.34 nM/mg/day) was comparable to the
      mean quotient reported previously in older psychotic patients treated with
      perphenazine alone. After addition of perphenazine, the median quotient of
      nortriptyline plasma level to nortriptyline dose (L/D) increased significantly
      (from 6.1 to 8.6). This change was inversely correlated with baseline
      nortriptyline L/D. The median ratio of E-10-OH-NT to nortriptyline plasma level
      decreased significantly (from 1.6 to 1.3), whereas the median ratio of Z-10-OH-NT
      to nortriptyline plasma level did not change significantly. These results are
      consistent with the known inhibition by perphenazine of the cytochrome P450 2D6
      (sparteine/debrisoquine hydroxylase), the major enzyme involved in the oxidative
      metabolism of nortriptyline, mostly through the formation of E-10-OH-NT. This
      complex alteration in the metabolism of nortriptyline induced by perphenazine
      emphasizes the relevance of measuring plasma levels not only of nortriptyline but
      also of its hydroxymetabolites in older patients who are more likely to be
      sensitive to their differing cardiovascular, anticholinergic, and cognitive
      effects.

PMID- 9241015
TI  - Suspected complication of treatment with venlafaxine.

PMID- 9241016
TI  - Symptomatic volunteers different from patients with depressive disorders?

PMID- 9241017
TI  - Serum and urine risperidone concentrations in an acute overdose.

PMID- 9241018
TI  - Risperidone in comorbid borderline personality disorder and dysthymia.

PMID- 9241020
TI  - Reevaluation of "Alprazolam and suicidal ideation: a meta-analysis of controlled
      trials in the treatment of depression".

PMID- 9241019
TI  - Exacerbation of hallucinogen-persisting perception disorder with risperidone.

PMID- 9241021
TI  - Effectiveness of clomipramine for obsessive-compulsive symptoms and chronic pain
      in two patients with schizophrenia.

PMID- 9241022
TI  - Can you provide a table of equivalences for benzodiazepines and other marketed
      benzodiazepine receptor agonists?

PMID- 9241023
TI  - Determinants of musculoskeletal flexibility: viscoelastic properties, cross
      sectional area, EMG and stretch tolerance.
AB  - Cross-sectional area, stiffness, viscoelastic stress relaxation, stretch
      tolerance and EMG activity of the human hamstring muscle group were examined in
      endurance-trained athletes with varying flexibility. Subjects were defined as
      tight (n = 10) or normal (n = 8) based on a clinical toe-touch test. Cross
      sectional area was computed from magnetic resonance imagining (MRI) images.
      Torque (Nm) offered by the hamstring muscle group, electromyographic (EMG)
      activity, knee joint angle and velocity were continuously monitored during two
      standardized stretch protocols. Protocol 1 consisted of a slow stretch at 0.087
      rad/s (dynamic phase) to a pre-determined final angle followed by a 90-s static
      phase. In the dynamic phase final angle and stiffness was lower in tight (28.0+/
      2.9 Nm/rad) than normal subjects (54.9+/-6.5 Nm/rad), P<0.01. In the static phase
      tight subjects had lower peak (15.4+/-1.8 Nm) and final torque (10.8+/-1.6 Nm)
      than normal subjects (31.6+/-4.1 Nm, 24.1+/-3.7 Nm, respectively)(P<0.01), but
      torque decline was similar. Protocol 2 consisted of a slow stretch to the point
      of pain and here tight subjects reached a lower maximal angle, torque, stiffness
      and energy than normal subjects (P<0.01). On the other hand, stiffness was
      greater in tight subjects in the common range (P<0.01). Cross-sectional area of
      the hamstring muscles and EMG activity during the stretch did not differ between
      the groups. However, lateral hamstring cross-sectional area was positively
      related to mid-range stiffness (P<0.05), but inversely related to final
      stiffness, peak torque and the toe-touch test (P<0.01). Final angle and peak
      torque in protocol 1 combined to improve the predictability of the toe-touch test
      (R2=0.77, P<0.001). These data show that the toe-touch test is largely a measure
      of hamstring flexibility. Further, subjects with a restricted joint range of
      movement on a clinical toe-touch test have stiffer hamstring muscles and a lower
      stretch tolerance.

PMID- 9241024
TI  - Anterior cruciate ligament strength. Can it be estimated by non-destructive
      testing?
AB  - For structural and material bone strength, non-destructive tests exist, while no
      such tests have been developed for ligaments. In the present study we compared
      the geometry and bone mineral content (BMC) of the rat tibia with the tensile
      strength of the anterior cruciate ligament (ACL). A significant correlation was
      found between the mediolateral diameter of the tibial condyle and ACL load to
      failure (r=0.83). Calculating the area of the condyle as an ellipse increased
      this correlation to r=0.93. No significant correlation was found to BMC. If this
      correlation is also found in humans, the mediolateral tibial head diameter may be
      used to estimate the strength of the ACL non-destructively.

PMID- 9241025
TI  - Muscle phosphocreatine repletion following single and repeated short sprint
      efforts.
AB  - Phosphocreatine (PCr) repletion following either single (1x6 s, n=7) or repeated
      (5x6 s, departing every 30 s, n=8) maximal short sprint cycling efforts was
      measured in separate groups of trained subjects. Muscle biopsies (vastus
      lateralis) were taken pre-exercise before warming up, and then at 10 s, 30 s and
      3 min post-exercise. After the 1 x 6 s sprint PCr concentration was respectively,
      55% (10 s; P<0.01), 69% (30 s; P<0.01) and 90% (3 min; NS) of the pre-exercise
      value (mean+/-SD) (81.1+/-7.4 mmol x kg(-1) DM), whereas after the 5x6 s sprints,
      PCr concentration was, respectively, 27% (10 s; P<0.01), 45% (30 s; P<0.01) and
      84% (3 min; P<0.01) of the pre-exercise value (77.1+/-4.9 mmol x kg(-1) DM). PCr
      concentration was correlated with muscle lactate at 30 s (r=-0.82; P<0.05) and 3
      min of recovery (r=-0.94; P<0.01) for the 1x6 s sprint, but not for the 5x6 s
      sprints. The extent of PCr repletion was significantly greater after the 5x6 s
      sprints than the 1x6 s sprint between both 10 s and 30 s and 30 s and 3 min,
      despite lower PCr levels at 10 s, 30 s and 3 min following the 5x6 s sprints.
      Full repletion of PCr is likely to take longer after repeated sprints than single
      short sprints because of a greater degree of PCr depletion, such that
      replenishment must commence from lower PCr levels rather than because of slower
      rates of repletion.

PMID- 9241026
TI  - Saliva and marathon running.
AB  - The aim of this study was to follow changes in saliva and serum after strenous
      prolonged exercise. Twenty individuals, three women and 17 men, 24-62 years old,
      well-trained but not at elite level, participating in the Stockholm Marathon,
      were selected for the study. Two of the subjects broke the race after 20 km.
      Three samples of saliva were collected, i.e. (i) just before the race, (ii)
      directly after the race, and (iii) 1 h after the race. Paraffin-stimulated whole
      saliva, resting non-stimulated whole saliva and citric acid-stimulated parotid
      saliva were investigated. In all three types of saliva, there was a decrease in
      secretion rate and only 14 of the 18 participants could produce resting non
      stimulated whole saliva directly after the race. The salivary concentration of
      chloride, phosphate, potassium, amylase, hexosamine, sialic acid and salivary
      peroxidase were significantly higher after than before the race. There were no
      significant changes in salivary pH and buffer capacity. The total protein
      concentration was increased in all types of saliva after the race. To conclude,
      there were several changes in the saliva composition just after the marathon, but
      most of the values were back to baseline after 1 h of rest. However, the values
      for sodium, calcium, phosphate, salivary peroxidase, amylase and salivary IgA
      were still elevated 1 h after the race.

PMID- 9241027
TI  - Effect of intensive training on lower leg structural strength: an in vivo study
      in ovariectomized rats.
AB  - The aim of this study was to investigate the effect of training on the in vivo
      tibial structural strength during the development of post-ovariectomy
      osteoporosis. Seventeen mature Wistar rats (215 g) were ovariectomized and
      randomized into two groups. The sedentary control group was kept cage confined,
      while 3 days postoperatively the trained group started treadmill running with
      high intensity for 1 h 5 days a week. All were given a low calcium diet (Ca
      0.01%). After 8 weeks the animals were anaesthetized and the right lower legs
      fractured during muscle contraction in three-point ventral bending. The left legs
      were fractured at the same level after removal of all soft tissues.
      Histomorphometry of the meta- and diaphysis of the distal tibiae was performed.
      Weight-gain was higher in sedentary (108 g) than in trained (61 g) rats
      (P<0.0001). There were no significant differences in mechanical results between
      the groups at in vivo or in vitro fracture. Correcting for weight-gain
      differences did not change these results. Histomorphometry showed no differences
      between the groups. Corticosterone was higher in trained than in sedentary rats
      (P<0.02), and corticosterone may have had a negative influence both on muscle and
      bone. The study could not show an effect of high intensity training in the early
      phase after ovariectomy on in vivo or in vitro fracture strength.

PMID- 9241028
TI  - Pregnancy in endurance athletes.
AB  - The purpose of the present study was to examine pregnancy and delivery among
      Finnish endurance athletes at the national top level. A questionnaire concerning
      first pregnancy was sent to 30 Finnish endurance athletes who had been at
      national top level in cross-country skiing, running, speed-skating or
      orienteering. Data on labour were collected retrospectively through a
      questionnaire and from the diaries in the hospital concerned. The next primipara
      in the diaries formed a member of the control group. Twenty-three athletes (77%)
      had regular menstrual cycles, seven (23%) had irregularities, and four of them
      had received hormonal treatment for this. Seven athletes (23%) had experienced
      spontaneous abortion during the first trimester in previous pregnancy. Sixteen
      (53%) did not notice any change in their exercise performance, three (10%)
      subjectively felt themselves to be in a better physical condition, and seven
      (23%) felt themselves to be in a worse condition than before the pregnancy. Four
      did not respond on the question. After delivery, 18 athletes continued to
      compete, the median interval being 8.2 months (range 2-24 months). Two of them
      (11%) achieved a better condition than before the pregnancy, 11 (61%) reached the
      same level and five (28%) did not achieve the same performance level. There were
      no significant differences in labour parameters between the athletes and
      controls. Endurance training had no harmful side-effects on the pregnancies or
      deliveries of the athletes. The effect of pregnancy on exercise performance is
      individual.

PMID- 9241029
TI  - Radial epicondylalgia ('tennis elbow'): treatment with stretching or forearm
      band. A prospective study with long-term follow-up including range-of-motion
      measurements.
AB  - Stretching or upper forearm bands were used in the treatment of radial
      epicondylalgia ('tennis elbow') in a prospective study of 185 patients. The two
      consecutive series did not differ with respect to, for example, age (median 43
      years), gender (57% men), symptom duration (mean 12 months) and symptomatic elbow
      (68% right), and were examined before and after 1 month of treatment, then at 3
      and 9 months, and at a long-term follow-up (44/33 months). The 94 stretching
      treated patients were instructed to perform home exercises twice daily, but were
      also treated at six physiotherapist sessions the first month. The other 91
      patients were told to use a prescribed proximal forearm band in daily activities
      as much as possible. Both treatments were successful with a continuous symptom
      reduction, but the outcome was statistically significant in favour of stretching
      at all follow-ups, as assessed by subjective evaluation on a visual analogue pain
      scale, tabulated pain and condition alternatives on questionnaires, and objective
      findings such as palpation tenderness at the radial epicondyle, the (Mills')
      'tennis elbow pain test', and range-of-motion. Practically all measured range-of
      motions were restricted in both groups before treatment and did increase with
      stretching during the follow-up period, while the various changes in the forearm
      band group were statistically non-significant.

PMID- 9241030
TI  - The effect of strapping on the motor performance of the ankle and wrist joints.
AB  - The purpose of this study was to examine the effect of strapping on different
      components of motor performance of wrist and ankle joints. The subjects were 14
      healthy volunteers (12 females, two males), aged 21-33 years, with no known
      previous injuries of the ankle and wrist joints. The measurements were made with
      the HPM/BEP system and Isokinetic Lido Active Multi-joint system. First, the
      subjects performed the test without strapping and then, on the following day,
      with strapped right wrist and ankle joints. The strapping of the wrist increased
      the simple reaction time by 9%, choice reaction time by 9% and decreased the
      wrist tapping speed by 21%. Wrist strength decreased in flexion (180 degrees/s)
      by 14% and ulnar deviation (180 degrees/s) by 8%. The strapping of the ankle
      increased the simple reaction time by 12%, choice reaction time by 9% and
      decreased foot tapping speed by 14%. Ankle strength in plantar flexion decreased
      in 60 degrees/s by 22% and 180 degrees/s by 14% and in inversion in 60 degrees/s
      by 28% and 180 degrees/s by 15%. These results suggest the strapping of ankle and
      wrist joints reduces motor performance in the above-mentioned directions as
      measured by the following parameters: simple reaction time, choice reaction time,
      tapping speed, and muscle strength.

PMID- 9241031
TI  - Ultrasonography-guided percutaneous core biopsy in Achilles tendon disorder.
AB  - Ultrasound-guided percutaneous core biopsy technique was studied in 15
      consecutive patients with chronic Achilles tendon disorder defined as persisting
      local pain during daily activities, localized pain and swelling on palpation 2-5
      cm proximal to the calcaneal insertion. Ultrasound verified widening of the
      tendon and low echogenous areas at the site of pain. Percutaneous biopsies were
      taken from both the low echogenous areas and the normoechogenic tendon tissue. Of
      104 core biopsies 99 were representative. Open biopsies were taken from the
      macroscopically injured and normal tendon for comparison. Core and open biopsies
      of the low echogenous and macroscopically injured tendon showed similar
      histopathology. In 10 patients the core biopsy was performed under local
      anesthesia with limited subjective symptoms. Five of these patients were operated
      18-41 days later. No adverse effect was found referring to the biopsy taken a few
      weeks prior to surgery. No complications occurred. We conclude that the
      percutaneous core biopsy, guided by ultrasound and performed under local
      anesthesia, can be used under clinical and experimental in vivo studies for
      improving knowledge on pathoanatomy and healing processes of the Achilles tendon.

PMID- 9241032
TI  - The anterior stress fracture of the tibia: an atrophic pseudoarthosis?
AB  - Histopathological examination of biopsies from the fracture site in two cases of
      anterior stress fractures of the tibia demonstrated no bone remodelling activity,
      absence of inflammatory cells, extensive fibrotic infiltration and local
      avascular bone necrosis. The biopsies were taken peroperatively from two elite
      soccer players who earlier had to stop training due to severe exertional pain.
      When non-operative treatment failed to heal the fractures within 1 year and 6
      months, respectively, surgery was performed in order to stabilize the fractures.
      Both subjects were relieved from exertional pain within 6 months of surgery.
      Consecutive radiographs showed the pattern of direct healing and 8 months
      postoperatively confirmed complete healing without callus formation. Both elite
      soccer players returned to pre-injury activity level. We suggest that the
      excessive fibrotic tissue ingrowth and hypovascularity under repetitive stress
      causes the delayed healing and histopathological signs similar to an atrophic
      pseudoarthosis. Treatment should consequently consider the pseudoarthrotic
      character of the anterior stress fracture of the tibia.

PMID- 9241033
TI  - Optimal and predicted anxiety in 9-12-year-old track and field athletes.
AB  - In an effort to determine the applicability of individual zone of optimal
      functioning (IZOF) theory in young athletes, state anxiety was assessed in 40
      track and field athletes (20 male and 20 female) from 9 to 12 years of age.
      Optimal anxiety was determined by having participants complete the state-trait
      anxiety scale for children (STAIC) with instructions to recall how anxious they
      felt prior to their best performance of the season. Twenty-four hours prior to
      three 'more important' and three 'less important' track meets, participants
      completed the STAIC under instructions to predict how anxious they would feel 1 h
      prior to the upcoming track meet. Actual precompetition anxiety was assessed 1 h
      prior to each meet. Self-ratings of performance were collected following each
      meet in which the athletes competed. Athletes were grouped by age (younger, 9-10
      years old); (older, 11-12 years old) and by gender for analysis. Analysis by
      independent t-tests indicated that predicted and actual precompetition anxiety
      values did not differ for either age or gender for the more important meets.
      However, the 11-12-year-old girls had higher (P<0.05) predicted and actual
      anxiety values in the 'less important' meets than all other groups. Significant
      correlations (P<0.05) between predicted and actual precompetition anxiety
      occurred in all groups for both the less important and more important meets
      (r=0.66-0.97), with the exception of the 9-10-year-old girls for less important
      meets (r=0.38, P>0.05). Of all the participants, 26% reported performing best
      when anxiety values were in the high range. Self-ratings of performance were not
      lower (P>0.05) in cases in which the athlete experienced high levels of
      precompetition anxiety. In summary, the present findings indicate that several
      aspects of IZOF theory apply to preadolescent athletes.

PMID- 9241034
TI  - Ovarian expression, cellular localization, and hormonal regulation of rat
      secretory phospholipase A2: increased expression by interleukin-1 and by
      gonadotropins.
AB  - It has been suggested that ovulation may constitute a cyclic inflammatory-like
      process and that gonadotropin-inducible intraovarian interleukin (IL)-1, an
      established mediator of inflammation, may play a central role in this regard. In
      support of this hypothesis, our group has been able to document the ability of IL
      1 to potently stimulate prostaglandin biosynthesis by cultured rat ovarian cells.
      Herein we explore the possibility that the prostaglandin-stimulating action of IL
      1 is due, in part, to the enhanced expression of ovarian secretory phospholipase
      A2 (sPLA2). A single sPLA2 transcript of 1.4 kilobases was noted in all
      extraovarian tissues of immature rat origin subjected to Northern blot analysis.
      However, only a barely detectable signal was apparent in ovarian tissue. In
      contrast, the more sensitive RNase protection assay revealed the unequivocal
      presence of ovarian sPLA2 transcripts. Cellular localization studies by way of in
      situ hybridization documented sPLA2 transcripts primarily in the granulosa cell
      of the periovulatory ovary. Molecular probing of untreated cultured whole ovarian
      dispersates disclosed spontaneous elaboration of sPLA2 transcripts as early as 20
      h after the introduction of cells into culture. Treatment of cultured whole
      ovarian dispersates with IL-1beta for 48 h produced a 1.7-fold increase (over the
      value in untreated controls) in the relative expression of sPLA2 transcripts (p <
      0.01) along with a 1.7-fold increase in media PLA2 activity (p < 0.01). A more
      marked increase was documented for IL-1beta-treated cultured isolated granulosa
      cells (12.5-fold increase, p < 0.001). Treatment of whole ovarian dispersates
      with an IL-1 receptor antagonist (IL-1RA) produced a reduction in the basal
      expression of sPLA2 transcripts (55% at the 5 microg/ml dose level; p < 0.01) and
      PLA2 activity (40%; p < 0.01), thereby suggesting basal endogenous IL-1-like
      bioactivity. Treatment of cultured whole ovarian dispersates with either hCG or
      FSH led to 2.6-fold (p = 0.056) and 3-fold (p = 0.029) increases in the abundance
      of sPLA2 transcripts, respectively, effects blocked by the concurrent presence of
      IL-1RA. These observations 1) document the immature rat ovary as a site of sPLA2
      gene expression, 2) localize the relevant transcripts to the postovulatory
      granulosa cell, 3) confirm the presence of functional secreted ovarian PLA2
      activity, 4) reveal PLA2 expression to be IL-1- and gonadotropin-dependent, and
      5) suggest the existence of endogenous PLA2-stimulating IL-1-like activity. These
      findings also suggest that the ability of hCG or FSH to up-regulate ovarian sPLA2
      transcripts may be due, in part, to the endogenous elaboration of IL-like
      activity.

PMID- 9241035
TI  - Allogeneic and xenogeneic transplantation of cryopreserved ovarian tissue to
      athymic mice.
AB  - Cryopreserved ovarian tissue has major applications for female oncology patients
      and for the development of genome resource banks. The objective of the present
      study was to develop a bioassay of cryopreserved ovarian tissue function after
      allogeneic and xenogeneic transplantation to ovariectomized athymic nude (nu/nu)
      Balb/C mice. Transplant function was assessed by examination of vaginal smears,
      number of live births, and posttransplant histology. Animals were sham operated
      (group I; n = 4) or ovariectomized (group II; n = 5) or were given transplants of
      either fresh (group III; n = 3) or cryopreserved (group IV; n = 4) Institute of
      Cancer Research-strain mouse ovarian tissue or cryopreserved sheep ovarian tissue
      (group V; n = 7). Vaginal smears were examined 5-7 times per week; the number of
      days between visualizations of epithelial cells in smears was 4.3 +/- 0.6 for
      group I, 8.6 +/- 3.8 for group II, 3.4 +/- 0.4 for group III, 3.3 +/- 0.5 for
      group IV, and 4.6 +/- 0.6 for group V. Epithelial cells were seen for 1.2-1.7
      consecutive days; this value was significantly different between groups III and
      V. Live births were recorded from 3 of 4 animals from group I, 0 of 5 animals
      from group II, 2 of 3 animals from group III, and 1 of 4 animals from group IV.
      In vivo function and long-term survival of cryopreserved ovarian tissue after
      allogeneic or xenogeneic transplant were confirmed by the examination of vaginal
      cytology, and offspring were derived from allografts.

PMID- 9241036
TI  - Equine oocyte competence for nuclear and cytoplasmic in vitro maturation: effect
      of follicle size and hormonal environment.
AB  - Equine oocyte competence after in vitro maturation (IVM) was investigated in
      terms of the diameter of the follicle of origin and the stage of the estrous
      cycle, with three criteria of maturation: nuclear stage after DNA Hoechst
      staining, meiotic spindle morphology after tubulin immunocytochemical staining,
      and cortical granule localization after lectin labeling. Seven successive in vivo
      ultrasound-guided follicular punctures were performed on 10 cyclic saddle mares,
      alternatively at the end of the follicular phase (after induction of ovulation
      with a gonadotropin injection) and in midluteal phase (with or without a
      gonadotropin injection). Expanded cumulus-oocyte complexes (COCs) were stained at
      collection, and compact COCs were stained after in vitro culture. They were
      observed under a confocal microscope. Successive punctures on one mare provided
      0.9 preovulatory COCs and 8 immature COCs per 22 days. Among the preovulatory
      oocytes, 55% had completed nuclear and cytoplasmic maturation, 86% of which
      displayed a normal meiotic spindle. Of the 262 oocytes cultured in vitro, 37%
      completed nuclear maturation. The nuclear and cytoplasmic maturation rate
      significantly increased with follicle diameter. The IVM rate tended to be higher
      in follicular phase and tended to increase in luteal phase with the gonadotropin
      injection. The meiotic spindle morphology was not significantly different between
      the classes of follicular diameters. This study provided the opportunity to
      increase the number of characterized oocytes collected per cycle and per mare.
      This is the first report showing the progressive acquisition of meiotic
      competence in the equine oocyte during antral follicle growth and is the only
      description of the equine meiotic spindle.

PMID- 9241037
TI  - Isolation and characterization of MPM-2-reactive sperm proteins: homology to
      components of the outer dense fibers and segmented columns.
AB  - Sperm from most mammalian species catalyze the formation of an aster of
      microtubules in the oocyte after fertilization. One component that may be
      involved in the regulation of sperm centrosomal activity in the oocyte is a
      phosphorylated protein complex (MPM-2-reactive sperm protein; MSP) with a
      molecular mass of 77-85 kDa identified by the MPM-2 antibody. The objective of
      this study was to compare the MSPs to a previously identified 85-kDa complex
      (ODF/CP85) that is a component of the outer dense fibers of the sperm midpiece
      and the segmented columns of the connecting piece. MSPs were isolated from boar
      sperm using a differential extraction procedure and preparative gel
      electrophoresis. Three mouse monoclonal and rabbit polyclonal antibodies were
      made to the isolated complex, and these antibodies labeled similar proteins in
      rabbit, bull, boar, and mouse sperm. Extraction and solubilization procedures for
      MSPs and ODF/CP85 required harsh chaotropic and reducing conditions. In addition
      to migrating at the same molecular mass on gels, proteins from each preparation
      labeled with MPM-2, an anti-ODF/CP antibody, and the anti-MSP antibody prepared
      in this study. Amino acid composition was similar to that reported previously for
      rat and bull ODF/CP85. Furthermore, immunolocalization by both fluorescent and
      transmission electron microscopy indicated that the MSPs are components of the
      outer dense fibers and probably the segmented columns of the connecting piece.
      Taken together, these results indicate that the MSPs are the previously
      identified 85-kDa complex of the outer dense fibers and connecting piece.
      Therefore, it is likely that any involvement of these proteins in the regulation
      of sperm centrosomal activity is through the process of connecting piece
      disassembly.

PMID- 9241038
TI  - Chronic administration of the environmental pollutant 4-tert-octylphenol to adult
      male rats interferes with the secretion of luteinizing hormone, follicle
      stimulating hormone, prolactin, and testosterone.
AB  - 4-Tert-octylphenol (OP) is a prevalent environmental pollutant that has been
      shown to exert both toxic and estrogenic effects on mammalian cells. The effects
      of OP on the reproductive system of adult male vertebrates are virtually unknown.
      In the present study, we investigated the effects of chronic exposure to OP on
      reproductive hormone secretion in the adult male rat and compared the results
      qualitatively with those observed in other male rats treated chronically with
      estrogen. We injected corn oil vehicle or OP (20 or 80 mg) or estradiol valerate
      (EV; 0.8 or 8 microg) in oil s.c. into 2-mo-old male rats thrice weekly for
      either 1 or 2 mo. The 80-mg dosage of OP and one or both dosages of EV had the
      following effects: decreased anterior pituitary gland (APG) and serum LH and FSH
      concentrations; increased APG and serum prolactin (PRL) concentrations; increased
      APG/body weight ratios; decreased serum testosterone concentrations; decreased
      hematocrit; and decreased food consumption and body weight gain. To evaluate the
      response of the hypothalamus-APG to gonadal removal, we orchidectomized some of
      the rats after the end of treatment and decapitated them 3 wk later. In
      orchidectomized controls, serum LH and FSH concentrations rose markedly and serum
      PRL concentrations decreased. Similar changes were seen in orchidectomized rats
      treated previously with 20 or 80 mg OP. Moreover, there were no differences in
      mean serum LH, FSH, or PRL concentrations between controls and rats treated
      previously with either dosage of OP at 3 wk after orchidectomy. The results
      demonstrate that chronic administration of OP to adult male rats can adversely
      affect the secretion of reproductive hormones and strongly suggest that OP exerts
      these effects by acting like an estrogen. The opposite changes in LH, FSH, and
      PRL secretion observed after cessation of treatment with OP and orchidectomy
      suggest that chronic treatment with OP under the conditions of the present study
      did not result in any significant permanent deleterious effects on gonadotrophs
      or lactotrophs or the hypothalamic neurons controlling the secretion of the
      gonadotropins or PRL.

PMID- 9241039
TI  - Chronic administration of 4-tert-octylphenol to adult male rats causes shrinkage
      of the testes and male accessory sex organs, disrupts spermatogenesis, and
      increases the incidence of sperm deformities.
AB  - The environmental toxicant 4-tert-octylphenol (OP) has been shown to exert
      estrogenic effects on mammalian cells in culture. Recent findings from our
      laboratories demonstrate clearly that OP administration disrupts reproductive
      hormone secretion in the adult male rat, quite likely as a result of estrogenic
      action. In the present study, we investigated the impact of these or other OP
      induced changes on male reproductive tissues. Adult male rats were injected with
      OP (20 or 80 mg) or estradiol valerate (EV; 0.8 or 8 microg) s.c. in oil three
      times a week for either 1 or 2 mo. We found that an 80-mg dosage of OP for 2 mo
      or an 8-microg dosage of EV for 1 or 2 mo greatly reduced sperm numbers and
      adversely influenced the sizes, weights, and histological structures of the
      testes, epididymides, ventral prostate glands, seminal vesicles, and coagulating
      glands. The 80-mg dosage of OP for 1 mo reduced epididymal tubule size to a
      lesser extent than after 2 mo of treatment. Otherwise, treatment with 80 mg OP
      for 1 mo, 20 mg OP for 1 or 2 mo, or 0.8 microg EV for 1 mo had little or no
      effect on the histology of the tissues we examined. Additional evaluation of
      sperm morphology revealed marked increases in the proportions of head and tail
      abnormalities from animals that had received 80 mg of OP or 8 microg of EV for 1
      mo and 20 mg of OP for 2 mo. The head abnormalities consisted mainly of pin
      heads, detached heads, and the absence of hooks, while tail abnormalities
      included mainly broken, coiled, and bent tails. Our results clearly demonstrate
      that OP can severely reduce the size and/or function of all of the male
      gametogenic and accessory reproductive organs studied. Moreover, the similarity
      of these cell and tissue changes between rats treated with OP and those treated
      with EV further suggests that OP may exert its action in an estrogenic-like
      manner.

PMID- 9241040
TI  - Follicle-stimulating hormone stimulates circulating gonadotropin surge
      attenuating/inhibiting factor bioactivity in cows.
AB  - This study aimed to determine whether superovulation in cattle stimulates
      gonadotropin surge-attenuating/inhibiting factor (GnSAF/IF) bioactivity, as it
      does in humans. Blood samples were collected from cows (n = 7 per treatment) at 
      4, 8, 20, 32, 44, 56, and 68 h after injections of saline, eCG, or FSH. Equal
      volumes of plasma at each treatment and time point were pooled, and GnSAF/IF and
      inhibin bioactivities were measured using an established rat pituitary cell
      culture bioassay. Plasma from saline- and eCG-treated cows had little effect on
      GnRH-induced LH secretion (116.3 +/- 8.3%-81.6 +/- 6.0% of control), while plasma
      from FSH-treated cows produced a time-dependent suppression of GnRH-induced LH
      secretion, falling to 64.6 +/- 4.0% of the control value at 56 h after first FSH
      injection (p < 0.001). The GnSAF/IF bioactivity from the 56-h plasma eluted at pH
      5.73 by pseudochromatofocusing-similar to the GnSAF/IF isoelectric point value of
      5.81 determined using serum from superovulated women. Plasma from FSH-treated
      cows reduced basal FSH secretion more than plasma from eCG-treated cows (to 55.5
      +/- 5.7% and 63.2 +/- 6.6% of the control value, respectively, p < 0.01) although
      immunoreactive inhibin concentrations were similar between the two groups. We
      conclude that FSH, but not eCG, treatment causes a time-dependent production of
      circulating GnSAF/IF bioactivity in cattle.

PMID- 9241041
TI  - Detection of transcripts for retinoic acid receptors, retinol-binding protein,
      and transforming growth factors during rapid trophoblastic elongation in the
      porcine conceptus.
AB  - Early conceptus development (Days 10-12) in the pig is characterized by rapid
      remodeling and elongation of the trophoblastic membrane. Endometrial synthesis
      and secretion of retinol-binding protein (RBP; transporter of retinol) into the
      uterine lumen parallels the rapid morphological transformation of the conceptus.
      Hence, retinoic acid, a powerful morphogen, may serve a critical function in
      trophoblastic remodeling and conceptus elongation through the various isoforms of
      retinoic acid receptor (RAR). We hypothesize that various transcripts for RAR
      will be expressed, possibly differentially, in the early developing porcine
      conceptus on Days 10-12 of gestation. Conceptuses were collected from pregnant
      gilts and individually frozen in liquid nitrogen after classification for
      morphological size. A total of 36 conceptuses (4 groups of 9) representing
      spherical (2-9 mm), early tubular (10-12 mm), late tubular (13-60 mm), and
      filamentous (> 100 mm) morphologies were assembled for qualitative assessment of
      mRNA for RAR alpha, RARbeta, RARgamma, RBP, and transforming growth factor beta
      (TGFbeta)-2 and -3 with reverse transcription polymerase chain reaction (RT-PCR).
      RBP gene expression was affected by stage of conceptus development (p < 0.05) as
      RBP expression increased in a linear fashion from 2-mm to 8-mm spherical
      conceptuses, decreased slightly in the tubular stage, and increased dramatically
      in filamentous conceptuses. RAR alpha, RARbeta, and RARgamma gene expression was
      evident at all stages of conceptus development. RAR alpha gene expression
      increased (p < 0.05) in a linear fashion from 2- to 8-mm spherical conceptuses,
      and expression plateaued in the 9- to 12-mm conceptuses. Expression of RAR alpha
      declined slightly at the tubular stage but dramatically increased in filamentous
      conceptuses. RARbeta gene expression was present across all stages of conceptus
      development although in diminutive amounts. RARgamma gene expression was evident
      in all stages of conceptus development but was not affected (p > 0.05) by
      developmental stage. Gene expression for TGFbeta-2 was not detected by RT-PCR at
      any stage of conceptus development, whereas TGFbeta-3 expression increased (p <
      0.05) from the 2- to 8-mm conceptuses and remained high throughout trophoblastic
      elongation into the filamentous stage. The presence of mRNA for the RAR alpha,
      RARbeta, and RARgamma in elongating porcine conceptus provides evidence that RAR,
      particularly RAR alpha, may function as an important acceptor for retinoic acid
      and possibly regulate gene expression prior to and during rapid trophoblastic
      elongation in the porcine conceptus.

PMID- 9241042
TI  - Pharmacokinetics and ovarian-stimulatory effects of equine and human chorionic
      gonadotropins administered singly and in combination in the domestic cat.
AB  - Pregnancy success and embryo survival are low with the use of assisted
      reproduction in felids treated with exogenous gonadotropins. In this study, the
      pharmacokinetics and ovarian-stimulatory effects of eCG and hCG were evaluated in
      the domestic cat. Catheterized anestrual queens (n = 4 per treatment [Trt] group)
      were given 100 IU eCG i.v. (Trt 1), 100 IU eCG i.m. (Trt 2), 75 IU hCG i.v. (Trt
      3), 75 IU hCG i.m. (Trt 4), or 100 IU eCG i.m. followed 80 h later by 75 IU hCG
      i.m. (Trt 5). Blood samples were collected at 0, 5, 30, and 60 min and 4, 8, 12,
      24, 36, 48, 72, 96, 120, 144, and 168 h postinjection, and serum samples were
      analyzed for estradiol-17beta, progesterone, eCG, and hCG. Pharmacokinetic traits
      (volume of distribution, Vd; elimination half-life, t1/2beta; clearance rate,
      Clr) were calculated for eCG and hCG. When i.v. and i.m. administration were
      compared, no differences (p > 0.05) were observed in follicle or corpus luteum
      (CL) number or hormone concentrations for queens receiving eCG or hCG alone.
      Number of mature ovarian follicles (> or = 2 mm diameter) observed at 168 h
      postinjection did not differ (p > 0.05) for eCG (mean +/- SEM, 10.5 +/- 2.0) vs.
      hCG (11.1 +/- 3.0), indicating that these were equally effective in inducing
      follicular growth. In most queens (> 90%) given single gonadotropins (i.m. or
      i.v.), eCG and hCG persisted in circulation for at least 120 h and 96 h after
      injection, respectively, reflecting similar (p > 0.05) pharmacokinetic (i.v.)
      values for Vd (eCG, 91.4 +/- 24.8 ml/kg; hCG, 59.1 +/- 7.9 ml/kg), t1/2beta (eCG,
      23.0 +/- 2.4 h; hCG, 22.9 +/- 4.1 h), and Clr (eCG, 2.7 +/- 0.5 ml/h per kg; hCG,
      1.8 +/- 0.1 ml/h per kg). Sequential treatment with eCG+hCG did not affect (p >
      0.05) the t1/2beta of individual gonadotropins. In summary, eCG and hCG have
      comparable pharmacokinetics and ovarian-stimulatory activity when administered
      alone to the domestic cat. These findings suggest that hCG promotes the ancillary
      follicle formation that is frequently observed after ovulation in cats treated
      with eCG+hCG regimens, possibly disrupting the maternal environment and
      decreasing fecundity following assisted reproductive procedures.

PMID- 9241043
TI  - Type-1 and type-2 cytokines in human late-gestation decidual tissue.
AB  - Evidence suggests that successful pregnancy in rodents requires the preferential
      stimulation of type-2 cytokine production by gestation-associated tissues. The
      ability of human gestation-associated tissue to synthesize type-2 and type-1
      cytokines has not been examined in detail and was the subject of this study.
      Decidual tissue collected at term, either before the onset of labor (elective
      caesarean section) or at the completion of labor, expressed mRNA for interleukin
      (IL)-10 and interferon gamma (IFN-gamma) and produced IL-10 and IFNgamma protein
      in vitro. IL-4 mRNA or protein was not detected. IFNgamma production in vitro was
      significantly decreased by decidual cells prepared from decidua collected after
      labor as compared with those collected before the commencement of labor, a change
      that may be associated with prostaglandin E2 (PGE2) production in conjunction
      with labor. IFNgamma, IL-4, and IL-10 were detectable in human amniotic fluid
      collected at term. There was no significant difference in the levels of IL-4,
      IFNgamma, or IL-10 in samples collected before labor onset or during labor. Thus,
      late-gestation human decidual tissue and amniotic fluid do not preferentially
      express a type-2 cytokine profile of cytokines. This is not consistent with
      observations of a predominant type-2 cytokine profile in gestation-associated
      tissues in murine pregnancy.

PMID- 9241045
TI  - Effect of the oxytocin antagonist atosiban (1-deamino-2-D-tyr(OET)-4-thr-8-orn
      vasotocin/oxytocin) on nocturanl myometrial contractions, maternal cardiovascular
      function, transplacental passage, and fetal oxygenation in the pregnant baboon
      during the last third of gestation.
AB  - The oxytocin antagonist, atosiban (1-deamino-2-D-tyr(OET)-4-thr-8-orn
      vasotocin/oxytocin), was infused i.v. to chronically instrumented pregnant
      baboons in the last third of pregnancy. Atosiban (6 microg/kg per min) inhibited
      myometrial electromyographic activity associated with spontaneous myometrial
      contractions that occurred around the onset of darkness between 134 and 162 days
      gestation (term 180 days gestation). The effect of atosiban on maternal heart
      rate was minimal. Maternal blood pressure remained unaltered during atosiban
      infusion. Fetal carotid arterial PO2 was unchanged during a 2-h infusion of
      atosiban. Transplacental passage of atosiban from mother to fetus was assessed at
      cesarean section under halothane anesthesia in four baboons and in two
      chronically instrumented fetuses in the absence of anesthesia. The maternal:fetal
      concentration gradient ranged from 9.2 to 22.8. Maternal atosiban clearance rates
      were 9.2-16.9 ml/kg per min. In conclusion, atosiban was very effective at
      inhibiting spontaneously occurring nocturnal myometrial contractions during the
      last third of gestation in the pregnant baboon. Although atosiban crosses the
      placenta relatively freely, there was no effect on fetal oxygenation.

PMID- 9241044
TI  - Embryonic abnormality caused by male pheromonal effect in pregnancy block in
      mice.
AB  - BALB/cA females mated with BALB/cA males and exposed to DDK males showed 100%
      pregnancy block when exposure started at Days 0-3 of pregnancy. When the exposure
      to DDK males started at Days 4, 5, 6, and 7, the pregnancy rate was 33.3%, 50%,
      90%, and 100%, respectively. (Hereafter, the BALB/cA females exposed to DDK males
      are referred to as the experimental females, and those exposed to other BALB/cA
      males as the control females.) Cell number of embryos at Day 3 of pregnancy from
      the experimental and control females after exposure starting from Day 0 was,
      respectively, 27.0 +/- 1.2 (mean +/- SEM) vs. 48.6 +/- 1.0 (p < 0.05) for the
      morulae and 34.8 +/- 1.3 vs. 64.1 +/- 2.0 (p < 0.05) for the blastocysts. Embryos
      from the experimental and control females after exposure starting from Day 3 or
      Day 4 were histologically examined after 24-h exposure. Poor development of
      trophoblast and inner cell mass was observed at Day 4 as general defects of the
      experimental embryos. In addition, about one third of the embryos were
      unexpectedly at the more advanced stages than the controls (abnormal
      overdevelopment). At Day 5, disintegration of the trophoblast layer and primitive
      endoderm was observed as common abnormalities of experimental embryos, but
      overdevelopment was not observed at this stage. Disturbance in trophoblast
      differentiation or failure of its maintenance may be the primary developmental
      defect displayed by embryos developing in a deteriorated uterine environment
      under the influence of the odor of alien males.

PMID- 9241046
TI  - An antigenically related polypeptide family is a major structural constituent of
      a stable acrosomal matrix assembly in bovine spermatozoa.
AB  - The apical and principal segments of the bovine acrosome contain a stable matrix
      complex that is bound to the outer acrosomal membrane and exhibits hydrolase
      binding activity. The present study was undertaken to determine whether the outer
      acrosomal membrane-associated matrix complex (OMC) is composed of a unique set of
      acrosomal proteins and to define its fate during both capacitation and the
      acrosome reaction. A purified OMC fraction was isolated from ejaculated
      spermatozoa, and one polypeptide of 32 kDa (OMC32) was purified to homogeneity
      and used for N-terminal sequence analysis and preparation of monospecific
      antisera. Immunofluorescence staining of sperm with anti-OMC32 demonstrated that
      the polypeptide localized specifically to the apical and principal segments of
      the acrosome. Immunoelectron microscopy further revealed that OMC32 was
      restricted to the stable matrix assembly and was not associated with the inner
      acrosomal membrane or the equatorial segment. Immunoblot analyses of sperm
      lysates and of the purified OMC fraction revealed that anti-OMC32 recognized an
      antigenically related family of polypeptides between 38 and 19 kDa. These
      polypeptides exhibited no size processing during capacitation or the acrosome
      reaction, and they were not released during the acrosome reaction but remained in
      the particulate cell subfraction, associated with the hybrid membrane complex. N
      terminal sequence analysis of OMC32 indicated a structural relationship to the SP
      10 polypeptide family of human and baboon spermatozoa. The potential function of
      the OMC complex and differences in the intraacrosomal distribution of bovine
      OMC32-related polypeptides from that reported for acrosomal SP-10 polypeptides in
      other species are discussed.

PMID- 9241047
TI  - Characterization of the onset of menopause in the rhesus macaque.
AB  - The objective of this study was to assess ovarian activity in a cohort of aged
      female rhesus macaques. Menstrual records for 26 rhesus macaques ages 20-29 yr
      were evaluated over a 1-yr period, and daily urinary estrone conjugate (E1C) and
      pregnanediol-3-glucuronide (Hygeia [Hy]-PdG) levels were determined for 12 wk.
      Each animal was categorized as either pre-, peri-, or postmenopausal based on
      menstrual and hormonal data. Eleven animals (mean age 22.5 yr) were
      premenopausal, thirteen (mean age 24 yr) were perimenopausal, and two (mean age
      29.5 yr) were postmenopausal. Hormone profiles for perimenopausal animals reveal
      prolonged follicular phases and/or a lack of patterned Hy-PdG dynamics.
      Breakthrough bleeding occurred in four of these perimenopausal animals. The
      postmenopausal animals were amenorrheic and exhibited low E1C levels (less than
      10 ng/mg creatinine). The results of this study illustrate that the decline of
      ovarian function in female macaques during the third decade of life parallels the
      menstrual and hormonal events associated with the climacteric in women, and that
      menopause does occur in rhesus macaques.

PMID- 9241048
TI  - Immunoneutralization of transforming growth factor alpha present in bovine
      follicular fluid prevents the suppression of the follicle-stimulating hormone
      induced production of estradiol by bovine granulosa cells cultured in vitro.
AB  - Growth factors such as transforming growth factors alpha (TGF alpha) and beta
      (TGFbeta) secreted by theca cells and present in bovine follicular fluid (bFF)
      have been implicated in granulosa cell growth and differentiation. We
      investigated these phenomena using two complementary approaches to evaluate the
      physiological contribution of TGF alpha and TGFbeta in the control of the FSH
      induced estradiol production in bovine granulosa cells from large follicles.
      Granulosa cells (3 x 10(5) viable cells/cm2) harvested from eCG-treated
      prepubertal calves were cultured (serum free) in wells containing 500 microl/cm2
      of defined Ham's F-12 medium supplemented with 0.5 ng/ml FSH for the first 3 days
      (37 degrees C; 95% air:5% CO2). In the first approach, the effects of individual
      addition of TGF alpha and TGFbeta at final concentrations of 1 x 10(-4) to 10
      ng/ml were determined on Day 4 of culture after stimulation of granulosa cell
      estradiol production with 6 ng/ml FSH. In a second approach, TGF alpha or TGFbeta
      was removed specifically from bFF (from large follicles > 10 mm) by
      immunoneutralization. Thereafter, effects of immunoneutralization of TGF alpha or
      TGFbeta (0, 0.1, 1, 10, and 100 microg/ml anti-TGF neutralizing antibody) present
      in bFF (2%) were determined on Day 4 of culture following stimulation of
      granulosa cell estradiol production with 6 ng/ml FSH. On Day 4, FSH increased (p
      < 0.001) granulosa cell estradiol production (0 vs. 6 ng/ml FSH). Addition of TGF
      alpha decreased the granulosa cell estradiol production after 6 ng/ml FSH
      stimulation in a dose-dependent manner (p < 0.001). In contrast, addition of
      TGFbeta had no effect on the granulosa cell estradiol production (p > 0.1) after
      the addition of 6 ng/ml FSH. Addition of bFF (2%) decreased (p < 0.0001) the FSH
      induced estradiol production by bovine granulosa cells. After
      immunoneutralization of TGF alpha in bFF, however, this suppressed FSH-induced
      estradiol production was restored to levels obtained in the absence of bFF, and
      this occurred in a dose-dependent manner (p < 0.05). Immunoneutralization of
      TGFbeta in bFF did not prevent (p > 0.1) the suppressive effect of bFF on FSH
      induced estradiol production. These results suggest that TGF alpha produced in
      vivo by large bovine follicles can act locally (auto/paracrine manner) to
      suppress granulosa cell estradiol production.

PMID- 9241049
TI  - Source of inhibin in ovine fetal plasma and amniotic fluid during late gestation:
      half-life of fetal inhibin.
AB  - Immunoactive inhibin (ir-inhibin) concentrations were determined in chronically
      catheterized sheep between 120 and 145 days gestation. Maternal plasma ir-inhibin
      concentrations remained basal (0.19 +/- 0.05 ng/ml) throughout the period of
      study. Immunoactive inhibin concentrations in male and female fetal plasma were
      elevated above those observed in maternal plasma, with the concentrations in
      plasma of male fetuses (7.38 +/- 0.04 ng/ml) being significantly greater (p <
      0.001) than those in female fetuses (1.07 +/- 0.14 ng/ml). The concentrations of
      ir-inhibin in amniotic fluid of ewes bearing male fetuses (10.93 +/- 1.55 ng/ml)
      were significantly greater than in ewes bearing female fetuses (2.81 +/- 0.32
      ng/ml; p < 0.05) but not significantly different from the concentrations in male
      fetal plasma. Immunoactive inhibin concentrations decreased following surgery in
      gonadectomized fetuses, to 3.25 +/- 0.99 ng/ml within 6 h, and remained at a mean
      value of 0.75 +/- 0.38 ng/ml from 24 h after gonadectomy. The half-life of
      circulating inhibin in fetal plasma, estimated from the decay curve during the
      first 6 h after surgery, was 3.94 +/- 0.88 h. There was a significant (p < 0.05)
      decrease in the concentration of ir-inhibin in amniotic fluid after gonadectomy;
      however, this decrease occurred gradually over 7 days, and ir-inhibin
      concentrations did not fall to those concentrations observed in fetal circulation
      at any time after gonadectomy. It is concluded that the major source of
      circulating ir-inhibin in male fetal plasma, but not in amniotic fluid, is the
      gonads.

PMID- 9241050
TI  - Epididymal maturation of chromatin in spermatozoa from control monkeys (Macaca
      fascicularis) and those treated with Cetrorelix, a gonadotropin-releasing hormone
      antagonist.
AB  - In order to examine changes in sperm chromatin upon epididymal maturation in the
      macaque epididymis (Macaca fascicularis), spermatozoa were obtained from six
      regions of the duct and examined for the state of their chromatin condensation by
      flow cytometry after staining with acridine orange. To see whether changes were
      affected by androgens, tissue was obtained from five monkeys treated with the
      gonadotropin releasing hormone (GnRH) antagonist Cetrorelix. Spermatozoa were
      recovered from treated and control animals after 16 days (at hemicastration) and
      another 9 days of treatment. Chromatin condensation of epididymal spermatozoa
      from controls displayed an increase upon maturation. After 16 days of GnRH
      antagonist treatment, spermatozoa in the caput epididymidis displayed greater
      fluorescence than those from controls, but this was reduced during epididymal
      transit to values found in the distal epididymal regions of the controls. It is
      concluded that epididymal chromatin condensation 1) is normal in GnRH-antagonist
      treated monkeys as long as sperm are being produced and 2) can compensate for
      poor testis function so that spermatozoa with normal states of chromatin
      condensation are found in the distal cauda epididymidis and probably the
      ejaculate.

PMID- 9241051
TI  - Estrogen-mediated mitochondrial cholesterol transport and metabolism to
      pregnenolone in the rabbit luteinized ovary.
AB  - We investigated the mechanisms of luteotropic actions of estradiol on
      steroidogenesis. To this end, we examined, in vitro, the metabolism of
      cholesterol from endogenous or exogenous sources for pregnenolone production in
      rabbit luteinized ovarian cell mitochondria isolated from pseudopregnant animals
      in various states of stimulation by estradiol. We found that estradiol-mediated
      regulation of mitochondrial cholesterol metabolism for pregnenolone production
      differs from the mechanisms of regulation reported for steroidogenic
      protein/polypeptide hormones in the following respects: 1) in the estradiol
      sensitive, luteinized-ovary, rabbit model, temporary blockage of cytochrome P-450
      cholesterol side-chain cleavage enzyme by aminoglutethimide treatment in vivo has
      no effect on mitochondrial pregnenolone production in vitro after the
      aminoglutethimide is removed, indicating no additional capacity for upstream
      cholesterol storage; 2) preincubating mitochondria at 37 degrees C fails to
      increase subsequent pregnenolone synthesis in response to the addition of
      isocitrate; and 3) exogenously added cholesterol does not readily enter the
      steroidogenic pool of cholesterol unless the endogenous cholesterol pool is first
      depleted. These new observations indicate that estradiol increases the usable
      steroidogenic cholesterol pool in rabbit ovarian mitochondria. Also, 1) they are
      consistent with a putative requirement for the participation of one or more
      estrogen-sensitive protein factors to enhance cholesterol trafficking to the
      inner mitochondrial membrane, and 2) they complement the observation of estrogen
      dependent expression of steroidogenic acute regulatory protein in rabbit luteal
      tissue.

PMID- 9241053
TI  - Relationships among oocyte-cumulus morphology, follicular atresia, initial
      chromatin configuration, and oocyte meiotic competence in the horse.
AB  - Horse oocytes with expanded (EX) cumuli appear to have greater meiotic competence
      than do horse oocytes with compact (CP) cumuli but are thought to come from
      atretic follicles. We evaluated the relationships among cumulus expansion,
      follicle viability, initial chromatin configuration, and meiotic competence of
      horse oocytes. Follicle walls were sectioned for histological examination, and
      the follicles were scraped to obtain the oocytes. Half of the oocytes were
      evaluated immediately and half were matured for 24 h in vitro. Cumulus expansion
      was significantly associated with follicle atresia. Initially, significantly more
      EX than CP oocytes had chromatin condensed into one mass within the germinal
      vesicle (CC configuration; 61% vs. 32%). After culture, significantly more EX
      than CP oocytes had matured (74% vs. 30%). The proportion of oocytes with the CC
      configuration was lowest in viable follicles and increased in follicles with
      slight to moderate atresia. The maturation rate of oocytes from viable follicles
      was significantly lower than for oocytes from follicles with slight or moderate
      atresia. The CC chromatin configuration appears to be associated with meiotic
      competence in horse oocytes. The association of follicle atresia with increased
      meiotic competence suggests that acquisition of meiotic competence is related to
      a loss of suppressive activity by the degenerating follicle.

PMID- 9241052
TI  - Differential distribution of the tight-junction-associated protein ZO-1 isoforms
      alpha+ and alpha- in guinea pig Sertoli cells: a possible association with F
      actin and G-actin.
AB  - To elucidate the significance of alpha- and alpha+ isoforms of the tight-junction
      associated protein ZO-1 in Sertoli cell tight junction regulation, taking into
      consideration that different isoforms are expressed in cells with different
      junctional morphologies, we investigated whether alpha- and alpha+ are
      differentially associated with junctions forming the continuous occluding zonules
      responsible for the blood-testis barrier, and/or with junctions forming the focal
      discontinuous occluding zonules. In addition, since Sertoli cells contact Sertoli
      cells and germ cells, we investigated whether each isoform is differentially
      associated with distinct classes of germ cells. Our immunoblot analyses of
      isolated seminiferous tubules, using affinity-purified polyclonal antibodies
      recognizing rat and human alpha- and alpha+, showed that guinea pig testis
      contained the two ZO-1 isoforms initially described in rat and human kidneys, and
      that alpha+ and alpha- were predominantly expressed during puberty and adulthood,
      respectively, indicating that alpha+ was predominant during periods of increased
      junction assembly/disassembly. We used the same antibodies and immunoperoxidase
      labeling on fetal, neonatal, pubertal, and adult guinea pig testes sections. Both
      isoforms were expressed at the site of Sertoli cell-Sertoli cell and Sertoli cell
      germ cell junctions in the seminiferous epithelium, before and after birth, and
      both were localized in continuous and in discontinuous tight junctions. However,
      the distribution of alpha- and alpha+ was not the same in different locations of
      the tight junctions. Only alpha- was incorporated into junctions joining the
      Sertoli cells to all classes of germ cells. The alpha+ involved junctions joining
      Sertoli cells to particular classes of germ cells, suggesting that Sertoli cell
      expression of ZO-1 isoforms could be regulated by unique germ cell-Sertoli cell
      contacts. Conversely, we found a correspondence between the distribution of F
      actin and ZO-1alpha+, indicating that the spatial organization of the subsurface
      actin accompanying cell junctions may affect alpha+/alpha(-)-plasma membrane
      association.

PMID- 9241054
TI  - Production of cloned lambs from an established embryonic cell line: a comparison
      between in vivo- and in vitro-matured cytoplasts.
AB  - Nuclear transfer procedures were used to determine the in vivo developmental
      potential of an ovine embryonic cell line isolated from the inner cell mass of a
      Day 8 blastocyst-stage embryo. This cell line possessed a differentiated
      epithelial-like cell morphology. In this study, a comparison was made between in
      vivo- and in vitro-derived oocytes used as recipient cytoplasts in the nuclear
      transfer procedure. Cultured cells were induced to quiesce and enter presumptive
      G0 before being used as donor karyoplasts between passages 8 and 16 of culture.
      After cell fusion, reconstructed embryos were cultured for 6 days in vitro in
      embryo culture medium. Blastocyst-stage embryos were subsequently transferred to
      synchronized recipient ewes (n = 37), and development was allowed to proceed to
      term. There was a significant effect of source of recipient cytoplast, with
      development being consistently greater with in vivo compared to in vitro
      cytoplasts in terms of, respectively, blastocysts produced (24.2 +/- 3.8% vs.
      17.1 +/- 2.3%; p = 0.1), Day 35 pregnancy rate (40.0% vs. 9.1 %; p < 0.05), and
      Day 35 embryo survival (19.4% vs. 4.5%; p < 0.05). A high proportion of fetuses
      died during late gestation (5 of 8). The major abnormalities were associated with
      the urogenital tract. However, three lambs were delivered alive following
      cesarean section on Day 147. One lamb, derived from an in vitro-matured oocyte,
      died after 10 min, while the remaining two from in vivo-ovulated oocytes are
      apparently normal and healthy. DNA microsatellite markers conclusively show that
      the three lambs are genetically identical and were derived from the embryonic
      cell line. In conclusion, some cells from this blastocyst-derived embryonic cell
      line are totipotent by nuclear transfer and can produce viable offspring.

PMID- 9241055
TI  - Changes in androgen secretion and luteinizing hormone pulse amplitude are
      associated with the recruitment and growth of ovarian follicles during the luteal
      phase of the bovine estrous cycle.
AB  - In cattle the development of large antral follicles occurs in two or three
      successive waves during the estrous cycle, with one follicle per wave selected
      for dominance. To test the hypothesis that negative feedback effects of steroids
      secreted by the dominant follicle are critical to the regulation of follicular
      waves, we examined temporal relationships among ovarian follicular growth,
      steroid secretion, and gonadotropin secretion. Follicular growth was monitored by
      ultrasonography. In the first experiment, blood was collected from 5 Holstein
      heifers every 8 h between Days 0 and 14 of the estrous cycle from both a jugular
      vein and the vena cava (to collect ovarian blood). Jugular samples were also
      collected every 12 min for 8 h during three periods (Days 3 or 4, 7 or 8, and 11,
      12, or 13; n = 6) to characterize the pulsatile pattern of LH secretion. Both
      estradiol and testosterone concentrations in the vena cava increased as pre-wave
      elevations in FSH concentrations decreased (p < 0.05) between Days 1 and 4 (first
      follicular wave) and between Days 9 and 12 (second follicular wave). LH pulse
      amplitude was greater during the second period of frequent blood collection (Day
      7 or 8, end of the growth phase of the first dominant follicle) compared to the
      other two periods (p < 0.05), suggesting that increased LH pulse amplitude may be
      important for the later stages of dominant follicle growth. In the second
      experiment, to determine whether ovarian steroids are secreted primarily by
      dominant follicles, blood samples were collected from the utero-ovarian veins
      draining ovaries with (n = 4) and without (n = 4) a dominant follicle during the
      first follicular wave. Testosterone, androstenedione, and estradiol
      concentrations in the utero-ovarian veins fluctuated in relation to the pattern
      of follicular growth (p < 0.05), and secretion was much greater from ovaries with
      a dominant follicle. In blood collected both from the vena cava and from the
      utero-ovarian veins, estradiol secretion reached a peak and started to decline
      before androgen concentrations peaked (p < 0.05), suggesting that the initial
      decrease in estradiol secretion from the dominant follicle is not due to a lack
      of androgen precursors. The results suggest that 1) a transient increase in LH
      pulse amplitude during the early-midluteal phase may be important for supporting
      the final stages of dominant follicle growth; 2) ovarian androgens, as well as
      estradiol, may play a critical role in the control of FSH secretion during waves
      of follicular development; and 3) the dominant follicle is responsible for
      fluctuations in circulating estradiol and androgens during follicular waves.

PMID- 9241056
TI  - Coordinate developmental expression of genes regulating sterol economy and
      cholesterol side-chain cleavage in the porcine ovary.
AB  - To investigate the coordinate developmental expression of low-density lipoprotein
      (LDL) receptor, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, sterol
      carrier protein 2 (SCP2), steroidogenic acute regulatory protein (StAR), and
      cytochrome P450 side-chain cleavage (P450scc) enzyme messages throughout the pig
      estrous cycle, RNase protection analysis was performed using homologous
      (partially cloned) porcine sequences. Total RNA was isolated from ovarian tissues
      from unstimulated prepubertal gilts and gilts stimulated with eCG (Day -3) and
      hCG (Day 0) to induce follicular growth and ovulation. Specific transcripts
      (relative to 18S rRNA) were quantified in immature ovaries, preovulatory
      follicles (> or = 5 mm), corpora lutea (CL), and corpora albicantia. As an index
      of steroidogenesis, tissue progesterone content (per microgram protein) was low
      in the unstimulated ovary and preovulatory follicles, and it began to increase 4
      days post-hCG, peaked at 12 days, and returned to preovulatory concentrations by
      20 days post-hCG. HMG-CoA reductase mRNA was expressed at low levels and did not
      change significantly throughout the estrous cycle. The amount of LDL receptor
      mRNA increased approximately 6-fold after eCG stimulation and was expressed at
      similar concentrations in both preovulatory follicles and functional CL.
      Expression of SCP2 mRNA did not differ among the four tissue types but tended to
      be highest in midcycle (Day 12) CL compared other stages of CL (p = 0.007). StAR
      mRNA expression was minimal in unstimulated ovaries, was higher in preovulatory
      follicles (p = 0.014), and then rose again in CL (p = 0.009 compared with
      unstimulated ovary). P450scc mRNA concentrations were low in unstimulated
      ovaries, increased in preovulatory follicles (p = 0.044), and increased further
      in CL (p = 0.001 compared with preovulatory follicles). P450scc and StAR mRNA
      levels correlated with progesterone levels (r = +0.37, p = 0.025, and r = +0.71,
      p < 0.001, respectively). The expression of LDL receptor, StAR, and P450scc
      messages showed a dramatic decline by Day 20 post-hCG (p = 0.002, p = 0.003, p =
      0.006, respectively, compared with CL) corresponding with functional regression
      of the CL. In summary, P450scc and StAR message expression are coordinately
      amplified during the pig follicular and luteal phase, whereas LDL receptor
      message after an initial increase is expressed at constitutively high levels,
      thus indicating a differential regulation of ovarian sterol-metabolizing genes
      during the steroidogenic life of the follicle and CL.

PMID- 9241057
TI  - Negative feedback potency of estradiol is increased in orchidectomized sheep
      during chronic nutrient restriction.
AB  - The effect of nutrient restriction on serum concentrations of the gonadotropins,
      on the pattern of LH secretion, and on sensitivity to estradiol (E2) was assessed
      in orchidectomized sheep (wethers). Thirty-six wethers (initial weight = 42.3 +/-
      0.6 kg) were fed to gain, maintain, or lose body weight (feeding groups G, M, and
      L, respectively; n = 12 wethers/group). After 7 wk of controlled feeding, G, M,
      and L wethers weighed 57.0 +/- 1.7, 42.5 +/- 0.6, and 36.6 +/- 0.8 kg,
      respectively. At the end of controlled feeding, serum concentrations of LH and
      FSH in M and L wethers were significantly higher than levels in G wethers. During
      Days 51-54 of controlled feeding, six animals from each feeding group received E2
      or vehicle as a continuous infusion. The pattern of LH secretion was assessed 48
      h after initiation of infusion. Although E2 infusion did not affect (p > 0.05) LH
      pulse frequency in G and M wethers, pulse frequency was reduced (p < 0.05) in L
      wethers receiving E2. These data indicate that serum concentrations of
      gonadotropins are increased in wethers fed to maintain or lose body weight. In
      addition, the negative feedback potency of E2 is enhanced during prolonged weight
      loss.

PMID- 9241058
TI  - Moderate and severe nutrient restriction has divergent effects on gonadotroph
      function in orchidectomized sheep.
AB  - The effect of plane of nutrition and estradiol (E2) on pituitary concentrations
      of GnRH receptor and GnRH receptor mRNA was assessed in orchidectomized sheep
      (wethers). As detailed in the companion paper, 36 wethers were fed to gain,
      maintain, or lose body weight. Six animals from each feeding group received E2
      (0.31 microg E2/50 kg per h) or vehicle during Days 51-54 of controlled feeding.
      Anterior pituitary tissue was collected at the end of infusion. Both moderate and
      severe nutrient restriction increased (p < 0.05) tissue concentrations of FSH and
      FSHbeta mRNA. Conversely, concentrations of GnRH receptor and receptor mRNA were
      not affected (p > 0.05) by plane of nutrition. Estradiol increased (p < 0.05)
      GnRH receptor and receptor mRNA in wethers fed to gain or maintain weight.
      However, this E2-induced response was not evident in wethers subject to severe
      nutrient restriction. These data demonstrate that severe, but not moderate,
      nutrient restriction suppresses E2-induced augmentation of tissue concentrations
      of GnRH receptor and GnRH receptor mRNA. Collectively, the data presented here
      and in the companion paper suggest that severe nutrient restriction leads to
      physiologic changes that render the hypothalamus increasingly sensitive to
      estrogenic stimulation, while the pituitary is made less responsive to steroidal
      inputs.

PMID- 9241059
TI  - Induction of apoptosis in equine chorionic gonadotropin (eCG)-primed rat ovaries
      by anti-eCG antibody.
AB  - We have established a model to examine the early events of apoptosis in small
      antral follicles in vivo. Immature female rats injected with 15 IU eCG, and
      subsequently (24 h later) with an anti-eCG antibody to induce gonadotropin
      withdrawal, displayed a significantly lower ovarian weight and increased
      incidence of follicular atresia and granulosa cell death, especially in small- to
      medium-sized follicles. Evidence of apoptosis was apparent in a significantly
      higher proportion of granulosa cells from antibody-treated rats, which exhibited
      membrane blebbing, nuclear and cytoplasmic condensation, fragmentation, and
      phagocytosis. In addition, there was a loss of the regular organization of the
      lamina densa in the follicular basement membrane. Degradation of DNA was
      consistently found by 24 h in the antibody-treated group, and ladders could be
      observed as early as 1 h after treatment. Although cell death was observed after
      antibody treatment in some larger antral follicles, the occurrence of apoptosis
      was less frequent. These results demonstrate that gonadotropin withdrawal in vivo
      rapidly induces apoptosis in small- to medium-sized antral follicles at the
      critical stage of development when atresia is commonly observed, suggesting that
      this model is ideal for studying apoptosis in the ovary.

PMID- 9241060
TI  - Protein kinase C- and Ca2+ ionophore-stimulated production of reactive oxygen
      species in mechanically dispersed isolated bovine luteal cells.
AB  - We measured the production of reactive oxygen species (ROS) using luminol
      horseradish peroxidase-induced chemiluminescence in mechanically dispersed cell
      suspensions from bovine corpus luteum (CL). Since other cell types besides luteal
      cells were present in crude cell suspensions from CL, cell preparations were
      purified by centrifugation on Percoll. Only cell suspensions that gave no
      significant response when stimulated with formyl-methionyl-leucyl-phenylalanine,
      a potent stimulator of ROS production by phagocytes, were used routinely. Basal
      ROS production by purified bovine luteal cell preparations was low but could be
      stimulated rapidly and in a dose-dependent manner by nanomolar concentrations of
      the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA),
      though only in cells purified by fractionation on Percoll. Luteal ROS responses
      to PMA were quenched by returning bovine erythrocytes to purified luteal cells,
      or by exogenous catalase or superoxide dismutase. The magnitude of the response
      to PMA varied markedly from one luteal cell preparation to another but appeared
      to be unrelated to the stage of the luteal phase of the CL from which the cells
      were prepared. The luteal ROS response to PMA was blocked by staurosporine, an
      inhibitor of PKC. Although the inactive phorbol ester (4alpha-phorbol
      didecanoate; 4alphaPDD) alone had little or no effect on luteal ROS production,
      4alphaPDD significantly potentiated the effects of submaximal concentrations of
      PMA in a dose-dependent manner. ROS production could also be stimulated by the
      Ca2+ ionophore A23187. This response was rapidly abolished by treatment with EDTA
      or EGTA. A23187 also augmented the response to submaximal PMA levels: however,
      pretreatment with 4alphaPDD did not significantly enhance the ROS response to
      A23187. In conclusion, we have shown that isolated bovine luteal cell suspensions
      are capable of generating a marked acute ROS response triggered by activation of
      PKC and/or elevation of cytosolic calcium.

PMID- 9241061
TI  - Oxytocin antagonist [1-D(CH2)5,Tyr(ME)2,Thr4,Tyr-NH2(9)]ornithine vasotocin
      inhibits oxytocin-induced prostaglandin F2alpha release in late-pregnant cows.
AB  - The affinity and specificity of an antagonist of oxytocin, [1
      D(CH2)5,Tyr(ME)2,Thr4,Tyr-NH2(9)]ornithine vasotocin (OTA), to oxytocin receptors
      (OTR) in bovine gestational endometrium was determined in displacement
      experiments with oxytocin (OT) and vasopressin (AVP) analogues and compared to
      myometrial OTR. OTA had the highest affinity in both tissues. The effect of OTA
      on OT-induced increase in plasma concentration of 13,14-dihydro-15-keto
      prostaglandin F2alpha metabolite (PGFM) was studied in 24 late-pregnant cows.
      Treatments consisted of i.v. saline; OT (50 IU); OTA (1200 microg); and OTA (400,
      1200, or 4000 microg) injected i.v. 5 min before OT (50 IU) (n = 4 each). Samples
      were collected from jugular vein at 15-min intervals for 30 min before and 3 h
      after the injection of OT. Progesterone was measured in once-daily samples taken
      for 7 days after the experiment. OT caused a twofold increase in plasma PGFM
      within about 60 min (p < 0.005), with levels returning to baseline at 150-180
      min; OTA (1200 microg) caused a gradual lowering of basal plasma PGFM over 180
      min (p < 0.05). The 400-microg or 1200-microg dose of OTA did not alter OT
      induced PGFM response, whereas the 4000-microg dose inhibited it almost
      completely (p < 0.005). Plasma progesterone declined after the experiment in all
      cows, with no differences among groups. Because OTA inhibits OT-induced release
      of endometrial prostaglandin F2alpha it may be a good tocolytic agent.

PMID- 9241062
TI  - Sperm from a variety of mammalian species express beta1,4-galactosyltransferase
      on their surface.
AB  - In mice, initial gamete recognition is mediated by the binding of sperm surface
      beta1,4-galactosyltransferase (GalTase) to a glycoprotein of the zona pellucida,
      ZP3. When sperm bind to the zona pellucida, ZP3 induces the acrosome reaction by
      aggregating GalTase. The acrosome reaction releases acrosomal enzymes allowing
      sperm to pass through the zona pellucida, bind to the egg membrane, and activate
      development. In addition to GalTase, there is evidence that other sperm proteins
      may also bind ZP3. Although fertilization in the mouse is morphologically similar
      to fertilization in most other mammalian species, the degree of parallelism at
      the molecular level is not well defined. Less information is available about the
      molecular details of fertilization in other species. The aim of this work was to
      determine whether sperm from other mammalian species express GalTase on their
      surface. We performed GalTase enzyme assays on sperm from six species, and all
      six expressed GalTase on their surface. The amounts of GalTase varied between
      species. Guinea pig, mouse, and rat sperm had higher levels of GalTase than
      bovine, porcine, and rabbit sperm. GalTase was localized by immunofluorescence on
      live and fixed sperm to the anterior portion of the sperm head in all species
      examined. This is the expected location for a receptor that binds the zona
      pellucida. Biotinylation of sperm surface proteins confirmed that GalTase
      detected by immunofluorescence and enzyme assay was expressed on the sperm
      surface. These results demonstrate that various mammalian species express GalTase
      on their surface and that it is found in the proper location to bind to the zona
      pellucida.

PMID- 9241063
TI  - Rhesus monkeys produced by nuclear transfer.
AB  - Genetically identical nonhuman primates can provide a powerful animal model for
      gene therapy and research activities where the physiological parameters directly
      or indirectly under study are heritable. Here we demonstrate that nuclear
      transfer is a viable technology for the production of identical rhesus macaques.
      Oocytes recovered from gonadotropin-treated females were enucleated by aspiration
      of the first polar body and underlying ooplasm, then activated by cycloheximide
      exposure. Individual diploid blastomeres, recovered from in vitro-fertilization
      produced embryos (either fresh or frozen-thawed) and used as nuclear donors, were
      injected under the zona pellucida of enucleated (chromosome-free) oocytes and
      fused by electric pulses. The reconstituted embryos were cocultured on buffalo
      rat liver cells before cryostorage and transfer to synchronized host mothers. Of
      the 9 females receiving a total of 29 reconstituted embryos, 3 became pregnant,
      with two live births resulting, one male and one female. The parentage of both
      infants was established unequivocally by genotype analysis at 7 highly variable
      short tandem repeat loci.

PMID- 9241064
TI  - Refractoriness to a static melatonin signal develops in the pituitary gland for
      the control of prolactin secretion in the ram.
AB  - Hypothalamo-pituitary disconnected (HPD) and control Soay rams were treated
      chronically for 48 wk with s.c., continuous-release implants of melatonin while
      under long days (16L:8D). The implants produced continuously elevated blood
      concentrations of melatonin 2-3 times higher than the normal nocturnal maximum.
      The long-term treatment induced a biphasic effect on prolactin secretion in both
      the HPD and control rams, with a marked decrease in the blood prolactin
      concentrations for 10 wk followed by a gradual increase. The introduction of a
      second melatonin implant after 20 wk failed to affect prolactin secretion. The
      treatment with melatonin also caused a dynamic effect on FSH secretion, but this
      occurred in the control rams only. Blood concentrations of FSH in the HPD rams
      were very low throughout, but there were minor changes in testicular diameter
      that were correlated with variations in prolactin. Overall, the results support
      the conclusion that 1) melatonin acts primarily in the pituitary gland to affect
      prolactin secretion, and partial refractoriness develops at this level for
      control of prolactin; and 2) melatonin acts most probably in the hypothalamus to
      affect gonadotropin secretion, and refractoriness develops at the level of the
      neural tissue regulating GnRH release for control of gonadotropins.

PMID- 9241065
TI  - Molecular cloning and hormone-dependent expression of rabbit Muc1 in the cervix
      and uterus.
AB  - The microenvironment of the endocervix is regulated by secretory (> 10-15 x 10(6)
      Da) and cell-surface (< or = 1 x 10(6) Da) mucins. A survey with antisense and
      sense (control) oligonucleotides for eight epithelial mucin genes revealed that
      only MUC1, an anti-adhesive protein believed to modulate immune function and the
      only transmembrane mucin for which molecular probes exist, is expressed in the
      rabbit cervix. pMUC7, a 500-base pair cDNA probe to the tandem repeat domain of
      human MUC1, was used to clone the cDNA for the rabbit homologue. Although the GC
      rich tandem repeat of rabbit Muc1 had only 40% sequence identity with its human
      counterpart, its transmembrane domain and cytoplasmic tail maintained 93%
      sequence identity with the same regions of human MUC1. Detection of restriction
      length polymorphisms confirmed the Lagomorpha Muc1 gene, like the human, is
      polymorphic. Temporal expression of Muc1 transcripts (2.4 kilobases) correlated
      closely with epithelial differentiation in the cervix. However, compared with the
      adult cervix, uterine endometrium expressed the highest levels of Muc1. In the
      endometrium, Muc1 was increased (p < 0.0004) by progesterone and returned to
      estrous levels by treatment with estrogen. Muc1 levels in the cervix were
      unaffected by ovarian steroids, confirming tissue-specific regulation of Muc1 in
      the lower reproductive tract.

PMID- 9241066
TI  - Role of prolactin in the regulation of macrophages and in the proliferative
      activity of vascular cells in newly formed and regressing rat corpora lutea.
AB  - The proliferative activity of vascular cells and the number of macrophages were
      studied in corpora lutea of cycling and pregnant rats after prolactin (PRL)
      administration or depletion with the dopaminergic agonist CB154. Pregnant rats
      showed a higher proliferative activity of the vascular cells in newly formed
      corpora lutea than did cycling rats in metestrus. When cycling rats were treated
      with PRL, the proliferative activity was equivalent to that of pregnant rats.
      Treatment of pregnant rats with CB154 decreased the proliferative activity of
      vascular cells to the level in cycling rats. Otherwise, the proliferative
      activity was not modified in cycling rats after CB154 treatment. This indicates
      that the increase in the proliferative activity of vascular cells in the corpus
      luteum of pregnancy was due to the twice-daily PRL surges induced by mating.
      Treatment of cycling rats with CB154 decreased the number of macrophages in both
      newly formed and regressing corpora lutea, whereas PRL treatment increased the
      number of macrophages in regressing corpora lutea. In pregnant rats, treatment
      with CB154 decreased the number of macrophages in both newly formed and
      regressing corpora lutea. These results suggest that both the preovulatory and
      the twice-daily PRL surges regulate the macrophage population in newly formed and
      regressing corpora lutea.

PMID- 9241067
TI  - Multivariate analysis of occult lymph node metastasis as a prognostic indicator
      for patients with squamous cell carcinoma of the oral cavity.
AB  - BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral
      cavity is reflected in its ability to metastasize to regional cervical lymph
      nodes. Patients with clinically negative cervical lymph nodes are believed to
      have a good prognosis; however, the prognosis of patients with lymph node
      metastasis occurring after excision or radiotherapy of the primary tumor is poor.
      METHODS: Univariate and multivariate analyses for occult lymph node metastasis
      (ONM) in 172 patients with clinically negative cervical lymph nodes were
      performed by the authors to elucidate the clinical and histologic tumor risk
      factors to enhance their ability to predict ONM. A multivariate Cox proportional
      hazards model and Hayashi's quantification theory type II were used to analyze
      prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's
      proportional regression model, the factors linked to cancer specific survival
      were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P
      = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes
      were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer
      specific survival was 94.0% for patients without lymph node metastasis, and 51.0%
      for patients with ONM (P < 0.0001, log rank test). The most significant
      predictors for ONM of each of the clinical and histologic factors, in descending
      order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration,
      degree of differentiation, number of mitotic figures, and type of growth by means
      of Hayashi's quantification theory type II. The presence or absence of ONM in 147
      of 172 patients (85.5%) was correctly predicted by the score at the point of
      intersection of the two curves, which was -0.03. Further investigation revealed
      that 28 of 32 new cases were differentiated accurately by means of this
      diagnostic system. CONCLUSIONS: The results of the current study suggest that
      this method of analysis can establish a reliable predictor of ONM, thereby
      facilitating correct choices for surgical procedures to enhance the survival
      rates of patients with clinically negative cervical lymph nodes.

PMID- 9241068
TI  - Undifferentiated carcinoma of the major salivary glands.
AB  - BACKGROUND: Undifferentiated carcinoma of the salivary glands is a rare disease,
      the incidence of which is highest among the Inuit of Greenland and North America.
      It was demonstrated to be closely related to Epstein- Barr virus (EBV) infection.
      However, the relation of EBV to this tumor has not been studied to any great
      extent here in Taiwan because of the small number of cases. METHODS: Twelve cases
      of undifferentiated carcinoma of the salivary glands from the period 1977-1996
      were retrieved from the cancer registry at National Taiwan University Hospital.
      The clinical data were analyzed retrospectively based on the medical records.
      Eleven formalin fixed, paraffin embedded tissue sections were used for in situ
      hybridization with an antisense probe complementary to EBV-encoded RNA 1 (EBER1).
      RESULTS: Ten of 12 tumors originated from the parotid gland and 2 from the
      submandibular gland. The patients' ages ranged from 22 to 63 years, with an
      average of 38.1 years. One patient was lost to follow-up, 2 patients died of
      metastatic disease, and the remaining 9 patients were all alive and disease free
      at last follow-up. The actuarial 5-year survival rate was 79.8%. In situ
      hybridization demonstrated EBER1 in 9 of the undifferentiated carcinomas with
      lymphoid stroma, but EBER1 was not demonstrated in the other 2 tumors without
      lymphoid stroma. CONCLUSIONS: Undifferentiated carcinoma with lymphoid stroma of
      the major salivary glands is closely associated with EBV. The mainstay of
      treatment is surgery and postoperative radiotherapy. The outcomes in this series
      were good except for two elderly patients who died of rapid and progressive
      distant metastases.

PMID- 9241069
TI  - Adenosquamous carcinoma of the liver: clinicopathologic characteristics and
      cytokeratin profile.
AB  - BACKGROUND: The clinicopathologic characteristics, biologic behavior, and
      histogenesis of primary adenosquamous carcinoma (ASC) of the liver have yet to be
      fully clarified. METHODS: Eight cases of ASC of the liver were analyzed both
      clinicopathologically and immunohistochemically using antibodies of cytokeratin
      (CK) 7, CK 8, CK 18, CK 19, and CK 903 (CK 5, CK 10, CK 11, and CK 14). The
      survival curve of the 6 patients with surgically resected ASC was compared with
      that of the 32 patients with common cholangiocarcinoma (CC). RESULTS: Most ASCs
      had invasive pathologic features, including venous invasion, lymphatic
      permeation, and intrahepatic metastases. There were lymph node metastases from 7
      tumors (88%), and most of the metastases were adenocarcinoma. All adenocarcinoma
      (AC) components were positive for both CK 7 and CK 19. The squamous cell
      carcinoma (SCC) components were positive for CK 7 in all cases but were positive
      for CK 19 in only 5 cases (62.5%). The ACs were positive for CK 903 in only 3
      cases (37.5%), whereas all SCCs were positive for CK 903. Almost all ACs were
      positive for both CK 8 and CK 18, whereas the SCCs were positive for CK 8 in only
      3 cases (37.5%) and for CK 18 in no cases. All 6 patients with surgically
      resected ASC died of the disease within 1 year postoperatively. Their survival
      curve was significantly worse than that of the 32 patients with common CC (P <
      0.001). The two patients on whom autopsy was performed also died within 1 year
      after diagnosis. CONCLUSIONS: ASC tended to have more aggressive biologic
      behavior and a poorer prognosis than common CC. The authors' immunohistochemical
      analysis of CK expression indicated that most of the ASCs of the liver that were
      studied developed from a squamous transformation of the preexisting CC.

PMID- 9241070
TI  - The clinical significance of p21(WAF1/CIP-1) and p53 expression in pancreatic
      adenocarcinoma.
AB  - BACKGROUND: Wild-type p53 protein activates the WAF1/CIP-1 (p21) gene, leading to
      G1 arrest after DNA damage. The authors investigated the relation of p21 and p53
      expression in pancreatic adenocarcinomas to disease stage, overall patient
      survival, and survival when chemotherapy or radiation therapy was given. METHODS:
      Paraffin embedded tissue sections of 75 ductal adenocarcinomas of the pancreas
      were immunostained for p53 and p21. Nuclear expression was scored as absent,
      focal (<10%), moderate (10-50%), or strong or diffuse (>50%). RESULTS: The median
      survival of patients whose pancreatic tumors expressed the p21 protein (43 of 75
      cases, 57%) was better than that for patients whose tumors were p21 negative (32
      of 75 cases, 43%) (median survival, 13.5 vs. 9.8 months, respectively; P = 0.23).
      No difference in survival was found with regard to p53 protein expression (43 of
      75 cases, 57%); however, strong p53 expression was significantly associated with
      advanced disease stage (70% in Stage IV vs. 13-28% in lower stages). Expression
      of p21 correlated with earlier clinical stage. Stage specific comparisons showed
      a trend toward increased survival among p21 positive tumor patients diagnosed at
      clinical Stages I and III but not among those diagnosed at Stage IV. Adjuvant
      chemotherapy or radiation improved survival significantly if tumors expressed p21
      or no p53. CONCLUSIONS: Expression of p21 is significantly associated with
      earlier clinical stage in pancreatic adenocarcinoma, perhaps accounting for the
      better survival observed in this patient group than among those whose tumors were
      p21 negative. Improved survival with either chemotherapy or radiation therapy was
      observed for patients whose tumors were p21 positive or p53 negative.

PMID- 9241071
TI  - Risk of squamous cell carcinoma and adenocarcinoma of the lung in relation to
      lifetime filter cigarette smoking.
AB  - BACKGROUND: Over the past few decades, the incidence of adenocarcinoma (AC) of
      the lung increased much more rapidly than that of squamous cell carcinoma (SCC)
      in men and women. During this time period, filter cigarettes with substantially
      reduced "tar" and nicotine yields in the smoke came to dominate the market.
      METHODS: The risk of SCC and AC in lifelong smokers of filter cigarettes relative
      to lifelong nonfilter cigarette smokers was assessed in a case-control study
      performed between 1977 and 1995 with 2292 lung carcinoma patients and 1343
      hospital controls who were current smokers. RESULTS: Odds ratios (OR) for SCC in
      male and female subjects who had smoked filter cigarettes exclusively during
      their lives were slightly reduced relative to lifetime nonfilter cigarette
      smokers in men (OR = 0.8; 95% confidence interval [CI], 0.5-1.2), and
      significantly reduced in women (OR = 0.4; 95% CI, 0.2-0.8). No reduction in risk
      was observed for AC of the lung in men or women. CONCLUSIONS: Evidence that the
      increasing predominance of AC over SCC may be due in part to the reduced risk of
      SCC (but not AC) associated with lifelong filter cigarette smoking is strongest
      in women; for men, further studies that include larger numbers of lifetime filter
      smokers are needed to confirm this finding. A lack of protection against AC from
      low yield filter cigarettes may result from smokers' "compensating" with deeper
      and more frequent inhalation, thereby increasing delivery of carcinogens to the
      peripheral lung. The smoke of modern cigarettes also contains higher
      concentrations of nitrosamines that primarily produce AC.

PMID- 9241072
TI  - Prognostic value of the immunohistochemical detection of p16INK4 expression in
      nonsmall cell lung carcinoma.
AB  - BACKGROUND: The product of the p16INK4/CDKN2/MTS1 (p16) controls the transition
      from the G1 phase to the S-phase in the cell cycle by inhibiting the
      phosphorylation of the retinoblastoma gene product. A lack of p16 expression has
      been reported in various cancer cell lines and tumors; however, there have been
      only a few reports on the prognostic significance of p16 alteration. The authors
      studied p16 expression in nonsmall cell lung carcinoma (NSCLC) and also examined
      its correlation with clinicopathologic features and prognosis. METHODS: p16
      expression was determined by immunohistochemical analysis of 115 paraffin
      specimens of primary NSCLC that were curatively resected. The immunohistochemical
      study was performed using the labeled streptavidin-biotin method with anti-p16
      rabbit polyclonal antibody. RESULTS: Thirty-one of 115 NSCLC specimens (27%)
      showed negative p16 staining. The frequency of negative p16 expression was
      significantly higher in squamous cell carcinoma (39.5%) than in adenocarcinoma
      (20.3%) (P = 0.026). There were no statistically significant differences in the
      p16 status with respect to age, gender, smoking history, histologic
      differentiation, or stage of the disease. The Kaplan-Meier survival curves
      demonstrated that patients with negative p16 expression survived for a
      significantly shorter period of time than those with positive p16 expression (P =
      0.043). p16 status was a significant prognostic factor, especially in patients
      with early stage disease (Stages I-II) (P = 0.039). CONCLUSIONS: A lack of
      p16INK4 expression in NSCLC was observed more frequently in squamous cell
      carcinoma than in adenocarcinoma, and also was found to be closely related to
      prognosis, especially in patients with early stage squamous cell carcinoma.

PMID- 9241073
TI  - Thiotepa for the treatment of thrombocythemia in patients with Philadelphia
      chromosome positive chronic myelogenous leukemia.
AB  - BACKGROUND: Patients with chronic myelogenous leukemia (CML) occasionally
      experience persistent thrombocythemia despite having adequate white blood cell
      (WBC) counts. Trimethylenethiophosphoramide (thiotepa) is an alkylating agent
      that significantly inhibits platelet production. METHODS: The authors studied the
      effects of thiotepa in eight patients with CML with persistent thrombocythemia.
      All patients had adequate WBC counts while receiving therapy for leukemia. The
      median age of the patients was 58 years, and all had received at least 2 prior
      therapy regimens for CML. Thiotepa was administered by intravenous infusion at a
      dose of 75 mg/m2 once every 2 to 3 weeks; doses were adjusted according to
      hematologic response. RESULTS: Seven patients were evaluable for response to
      thiotepa. Their pretreatment median platelet count was 1215 x 10(9)/L. After
      receiving the first dose, 6 patients (86%) had favorable responses as the median
      platelet count dropped to 348 x 10(9)/L (P = 0.02). However, all the patients'
      platelet counts returned to near baseline values after the first course. Patients
      required a median of three courses to achieve stable platelet counts near the
      normal range. In 4 patients (57%), administration of thiotepa was discontinued
      because of a stable normal platelet count after a median of 7.5 courses; 1
      patient was still receiving treatment at last follow-up (18 courses) and 2
      patients stopped receiving treatment after their disease progressed to the
      blastic phase. Toxicity was mostly hematologic, with neutropenia (< or = 1 x
      10(9)/L) occurring during 5 of the 64 courses (8%) administered but only 1
      patient's course was complicated by fever. CONCLUSIONS: The authors conclude that
      thiotepa is useful in controlling thrombocythemia in CML patients who have
      elevated platelet counts despite having adequate WBC counts.

PMID- 9241074
TI  - A Phase I clinical trial of immunotherapy with interferon-gamma gene-modified
      autologous melanoma cells: monitoring the humoral immune response.
AB  - BACKGROUND: Tumor cells transduced with cytokine genes provide immunogenic
      vaccines for cancer immunotherapy. METHODS: A Phase I clinical trial was
      conducted for the specific active immunization of melanoma patients with
      interferon-gamma (IFN-gamma) gene-modified autologous melanoma tumor cells. Short
      term melanoma cultures were transduced retrovirally with the gene for human IFN
      gamma. The genetically modified melanoma cells secreted biologically active IFN
      gamma and showed enhanced expression of major histocompatibility complex class I
      and class II surface antigens. These cells were inactivated by irradiation (50
      gray) and were cryopreserved for the vaccine. Twenty melanoma patients were
      enrolled in this clinical trial. The immunizations were administered in
      escalating doses once every 2 weeks for 3 months. The first and second injections
      consisted of 2 million cells, followed by 6 million for the third and fourth
      injections, and then 18 million for the fifth and sixth injections. The humoral
      immune responses of the patients were assessed by enzyme-linked immunoadsorbent
      assay, radioimmunoassay, and radioimmunoprecipitation. RESULTS: Thirteen of the
      20 patients completed the immunization protocol. Eight of these 13 patients
      showed a humoral immunoglobulin (Ig)G response against autologous and allogeneic
      melanoma cells. The other five patients either had no detectable antimelanoma
      antibodies or showed a weak IgG response that did not rise significantly above
      the preimmune level. All the sera contained low or undetectable levels of
      antimelanoma IgM antibodies. The IgG response increased progressively in titer
      during the course of immunization. The positive sera showed preferentially strong
      binding to melanoma cell lines and some cross-reactivity to nonmelanoma tumors. A
      75-80 kD antigen on melanoma cells was immunoprecipitated by postimmune sera of 3
      of the responding patients. Preimmune sera from these three patients and sera
      from other patients immunized with a standard nontransduced melanoma cell vaccine
      failed to precipitate this antigen. Two patients with significant increases in
      serum IgG had clinical tumor regression, and two additional patients with low
      serum IgG response had transient shrinkage of nodular disease during therapy.
      CONCLUSIONS: These data suggest that gene therapy with IFN-gamma-transduced
      melanoma cells is safe and worthy of further investigation in patients with less
      advanced stage malignant melanoma. The ability to monitor changes in the humoral
      responses of the immunized patients has been demonstrated.

PMID- 9241075
TI  - Age-related differences in breast carcinoma knowledge, beliefs, and perceived
      risk among women visiting an academic general medicine practice.
AB  - BACKGROUND: This study assessed whether age-related differences in breast
      carcinoma knowledge and perceived risk exist among women in a primary care
      setting and whether these women's beliefs about the best age to begin screening
      mammography reflect those of their physicians. METHODS: Consecutive women ages 30
      70 years who visited an academic general medicine practice were asked to complete
      a questionnaire assessing breast carcinoma knowledge, beliefs, and perceived
      risk. Women's risk estimates were compared with individual risk probabilities
      derived from the Gail model. Women's beliefs about when to begin screening
      mammography were compared with the beliefs of the attending physicians in the
      practice. Questionnaire results were compared across age groups. RESULTS: Six
      hundred seventy-four women completed the survey. Overall, knowledge scores were
      negatively correlated with age (correlation coefficient = -0.30, P = 0.001). The
      level of knowledge about the benefits of mammography was high across all age
      groups. In contrast, knowledge that breast carcinoma incidence increases with age
      was poor. Only 28% of all women recognized that breast carcinoma is more common
      among women age 65 years than among women age 40 years. Among all women, 26%
      underestimated their risk of developing breast carcinoma in the next 10 years,
      32% correctly estimated their risk, and 42% overestimated their risk. Fifty-five
      percent thought that mammography should begin when a woman is age 30-35 years. In
      contrast, all surveyed physicians recommended that a woman start undergoing
      mammography at age 40 years or older. CONCLUSIONS: In this primary care setting,
      older women had poorer breast carcinoma knowledge than younger women but were
      equally likely to appreciate the benefits of mammography. Most women were unaware
      that age is a risk factor for breast carcinoma. Improved education of females by
      their physicians may resolve some of the observed discrepancies regarding the
      optimal age to begin screening mammography.

PMID- 9241076
TI  - Expression of interleukin-1beta in human breast carcinoma.
AB  - BACKGROUND: Interleukin 1beta (IL-1beta) is a multifunctional cytokine that up
      regulates the inflammatory response. It is not known whether IL-1beta plays a
      major role in human malignancy. To determine whether IL-1beta might be involved
      in breast carcinoma progression, the authors measured the IL-1beta content in
      tissue extracts from >200 invasive breast carcinomas and smaller numbers of
      ductal carcinoma in situ (DCIS) and benign lesions. METHODS: IL-1beta content was
      measured by an enzyme-linked immunoadsorbent assay and analyzed to determine
      whether these values were correlated with the contents of scatter factor (SF) (an
      invasogenic and angiogenic cytokine), von Willebrand's factor (VWF) (a marker of
      endothelium), thrombospondin-1 (TSP1) (an antiadhesive and antiangiogenic
      glycoprotein), and tumor necrosis factor-alpha (TNF alpha) (another
      proinflammatory cytokine). Studies were also performed to determine whether IL
      1beta content was correlated with other pathologic and immunochemical variables
      that have been utilized or proposed as prognostic indicators for breast
      carcinoma. RESULTS: The most important findings of these studies were: 1)
      immunoreactive IL-1beta was detected in approximately 90% of invasive breast
      carcinomas; 2) IL-1beta levels were significantly higher in invasive carcinomas
      than in a group of DCIS and benign lesions; 3) high IL-1beta content in invasive
      carcinomas was significantly associated with higher contents of SF, VWF, and
      TSP1, but not TNF alpha; and 4) there was a trend toward higher IL-1beta content
      in invasive carcinomas with a group of other parameters that suggest a
      biologically more aggressive tumor (estrogen receptor negativity, high tumor
      grade, p53 positivity, and bcl-2 negativity); and the proportion of invasive
      tumors with these characteristics was significantly increased in a subgroup of
      tumors having very high IL-1beta content. The authors also found a correlation
      between high IL-1beta content and CD68 positivity, suggesting that macrophages
      may account for some of the IL-1beta present in human breast carcinoma tissue.
      CONCLUSIONS: These findings suggest that significant titers of IL-1beta are
      present within the microenvironment of most breast carcinomas and that a high IL
      1beta content is often associated with tumor invasiveness and with other
      pathologic features suggestive of an aggressive tumor biology.

PMID- 9241077
TI  - Influence of BRCA1 mutations on nuclear grade and estrogen receptor status of
      breast carcinoma in Ashkenazi Jewish women.
AB  - BACKGROUND: In the Ashkenazim, three recurrent germline mutations have been
      identified in the breast carcinoma susceptibility genes BRCA1 and BRCA2:
      185delAG, 5382insC (BRCA1), and 6174delT (BRCA2). The frequency of these
      mutations in the general Ashkenazi population approaches 2%. There is little
      available controlled data comparing the characteristics of breast carcinoma
      arising in BRCA1 mutation carriers or BRCA2 mutation carriers with that arising
      in noncarriers, although such data would be relevant to the urgent clinical need
      to develop risk-reduction strategies for individuals at increased risk due to
      genetic factors. METHODS: The authors screened 149 unselected tumors arising in
      Ashkenazi Jewish women for the 185delAG, 5382insC, and 6174delT mutations and
      compared tumors arising in mutation carriers with tumors arising in noncarriers
      with respect to nuclear grade, steroid hormone receptor status, and axillary
      lymph node status. RESULTS: In the 149 cases, the authors found 17 BRCA1
      mutations (11.4%; 95% confidence interval [ci], 6.8-17.6%), and 4 6174delT BRCA2
      mutations (2.7%; 95% CI, 0.8-6.7%). Tumors from women with BRCA1 mutations were
      significantly less likely to be estrogen receptor positive (age-adjusted odds
      ratio [or]: 0.091; P < 0.001) and more likely to have a high nuclear grade (OR:
      5.55; P 0.001) than tumors in which no mutation was identified. All four BRCA2
      positive breast carcinoma specimens were estrogen receptor positive. CONCLUSIONS:
      Breast carcinoma arising in Ashkenazim BRCA1 mutation carriers has adverse
      prognostic features relative to those arising in noncarriers in the same
      population. This may be relevant to the development of prevention and treatment
      strategies for these women. For example, if tamoxifen reduces the risk of breast
      carcinoma via its antiestrogenic effects, it is possible that this effect will be
      diminished in the largely estrogen receptor negative BRCA1-related hereditary
      breast carcinoma.

PMID- 9241078
TI  - Interstitial iodine-125 radiation without adjuvant therapy in the treatment of
      clinically localized prostate carcinoma.
AB  - BACKGROUND: This study was designed to evaluate the efficacy of iodine-125
      interstitial radiation in the treatment of prostate carcinoma classified as T1 or
      T2. METHODS: One hundred twenty-six consecutive patients with adenocarcinoma of
      the prostate (T1, 23%; T2, 77%) were treated with iodine-125 radionuclides
      between January 1, 1988, and December 31, 1990. Four patients died of
      intercurrent illness within 1 year postimplant, leaving 122 men in the study. The
      prescribed minimum radiation dose was 160 gray. Median follow-up was 69.3 months.
      Prebiopsy prostate specific antigen (PSA) values (median, 5.0 ng/mL) were
      available for all patients. Posttherapy evaluation included clinical, biochemical
      (PSA), and pathologic (repeat needle biopsy) studies. No patient was surgically
      staged, and none received androgen deprivation therapy. Morbidity was graded
      according to the Radiation Therapy Oncology Group grading scale. Statistical
      appraisal was performed by the Kaplan-Meier method. PSA failure was defined in
      two ways: (1) PSA progression, i.e., 2 consecutive increases from a nadir value;
      and (2) failure to attain an arbitrary serum PSA value of 1.0 or 0.5 ng/mL at
      last follow-up. RESULTS: The overall 7-year survival was 77%; there were no
      deaths from prostate carcinoma in this cohort. The 7-year actuarial PSA
      progression free outcome was 89%, and the PSA < or = 1.0 ng/mL outcome was 87%.
      When PSA < or = 0.5 ng/mL was selected as an outcome end point, and PSA values in
      this series of radiation-treated patients were compared with PSA values proposed
      to indicate disease free survival after radical prostatectomy (PSA < or = 0.3-<
      or = 0.6 ng/mL), the 7-year actuarial disease free survival was 79%. Morbidity
      was minimal except in patients who had preimplant or postimplant transurethral
      prostate resection. CONCLUSIONS: Outpatient-based iodine-125 prostate
      brachytherapy for prostate carcinoma classified as T1 or T2 resulted in
      biochemical outcomes comparable to end points resulting from radical
      prostatectomy and external beam radiation.

PMID- 9241079
TI  - Sexual functioning after treatment for testicular cancer: comparison of treatment
      modalities.
AB  - BACKGROUND: This retrospective study evaluates changes in sexual functioning
      after treatment for testicular cancer and investigates whether there is a
      relationship with different treatment modalities. METHODS: A self-reported
      questionnaire was sent to 337 men who had been treated for testicular cancer at
      the University Hospital Groningen between 1977 and 1994. Medical information was
      obtained from the patient records. RESULTS: A response was received from 287 men
      (85%); 264 patients were included in this study (78%). The mean patient age at
      follow-up was 37.7 years (range, 17-71 years). The mean follow-up period was 6.7
      years (range, 0.25-18 years). Decrease in sexual functions was reported by 40% of
      patients (decrease in libido: 19%; arousal: 12% erection: 12.5%; orgasm: 19%; and
      ejaculation: 26%). Moreover, 23.5% of patients responding reported decreased
      sexual activity and 12.5% were dissatisfied with their sexual functioning.
      Patients with Stage II-IV nonseminoma who had been treated with polychemotherapy
      (PCT) with or without resection of residual retroperitoneal tumor mass (RRRTM)
      (PCT +/- RRRTM) reported a significantly sharper decrease in sexual functioning
      than patients who had been followed with a wait-and-see policy (W & S) (Stage I
      nonseminoma patients). It was noteworthy that patients treated by PCT alone
      reported more sharply decreased sexual functioning than patients treated by PCT +
      RRRTM. Patients treated by radiotherapy (Stage I-IIA seminoma) did not report
      findings significantly different from the W & S group. CONCLUSIONS: Testicular
      cancer patients are at risk for reduced sexual functioning, especially when
      treated by chemotherapy, with or without resection of residual tumor. Although
      chemotherapy may influence somatic aspects of sexual functioning, it appears that
      psychologic factors arising from the confrontation with testicular cancer play a
      strongly mediating (if not determining) role.

PMID- 9241080
TI  - Paclitaxel-based second-line therapy for patients with advanced chemotherapy
      resistant bladder carcinoma (M1): a clinical Phase II study.
AB  - BACKGROUND: In a previous clinical trial, the authors disclosed that the
      expression of tumor cell motility factor gp78hAMFR correlates with tumor
      progression in patients with bladder carcinoma. This study was initiated to
      evaluate whether the combination of cytostatic drugs with an antimotility factor
      has an effect on chemotherapy-resistant bladder carcinoma. METHODS: In a Phase II
      trial, the authors evaluated the influence of paclitaxel, carboplatin, and an
      antimotility factor (acellular pertussis vaccine [APV]) in 18 patients with
      cisplatin- and methotrexate-resistant metastatic bladder carcinoma. Intramuscular
      injection of APV 3 times in the first week, on Days 1, 4, and 7, was followed by
      paclitaxel 135 mg/m2 and carboplatin 400 mg/m2. After an interval of 1 week APV
      was given again on Days 15 and 19. Each cycle lasted 3 weeks. On Day 22 the cycle
      was repeated. RESULTS: Four of 18 patients had objective responses (2 had
      complete remissions and 2 had partial remissions). After a median number of 2.5
      cycles, side effects did not exceed World Health Organization Grade 4.
      CONCLUSIONS: The results of this clinical Phase II study demonstrate that the
      combination of paclitaxel-based therapy causes complete remissions previously not
      obtained with second-line chemotherapy, although no conclusions can be drawn as
      to the effectiveness of the individual substances. Further trials have to be
      evaluated with regard to the individual components.

PMID- 9241082
TI  - Lymphoma of the nasal cavity and paranasal sinuses: improved outcome and altered
      prognostic factors with combined modality therapy.
AB  - BACKGROUND: Lymphoma of the nasal cavity and paranasal sinuses is a rare
      presentation of extranodal lymphoma with a natural history that is not well
      characterized in this era of combination chemotherapy. The goals of this
      retrospective study were 1) to define the natural history of sinonasal lymphomas;
      2) to compare the results of radiation therapy (XRT) alone with those of combined
      modality therapy (CMT) in the treatment of patients with lymphoma of the nasal
      cavity and paranasal sinuses; and 3) to define prognostic factors for each
      treatment. METHODS: Between 1947 and 1993, 70 patients with newly diagnosed
      lymphoma of the nasal cavity and paranasal sinuses were treated. The Ann Arbor
      stages were: Stage IE: 42 patients; Stage IIE: 14 patients; Stage IIIE: 2
      patients; and Stage IV: 12 patients. The distribution of T classifications of the
      primary tumors was as follows: T1: 2 patients; T2: 16; T3: 18; and T4: 34.
      Greater than 90% of the patients had intermediate grade lymphoma (Working
      Formulation), and none had follicular lymphoma. Twenty-eight patients received
      XRT alone, and 42 received CMT. RESULTS: The actuarial 5-year freedom from
      progression (FFP) and overall survival (OS) rates for the entire group were 57%
      and 52%, respectively. For patients with localized disease (Stages IE and IIE)
      receiving CMT, the actuarial 5-year FFP and OS were 83% and 67%, respectively. In
      multivariate analysis, treatment with CMT (P = 0.0005) and stage (IE vs. IIIE-IV)
      (P = 0.0001) were associated with improved FFP. In the group of patients
      receiving XRT, extent of disease (Stage IE, T1-3 vs. Stage IE, T4 vs. Stage IIE
      IV) (P = 0.0001) was the only clinical characteristic associated with improved
      FFP in multivariate analysis. For patients receiving CMT, International Index (0
      vs. 1-3 vs. 4, 5) (P = 0.0001) was the only significant factor predictive of
      improved FFP in multivariate analysis. One patient failed in the central nervous
      system (CNS) after initial therapy as a result of a radiation therapy marginal
      miss. CONCLUSIONS: In a Western population, patients with localized lymphoma of
      the nasal cavity and paranasal sinuses have a favorable prognosis when treated
      with CMT. FFP is significantly improved by treatment with CMT. For patients
      treated with XRT, extent of disease is the strongest predictor of outcome.
      International Index is the most significant prognostic factor for patients
      receiving CMT. Failure in the CNS is rare after initial therapy and is associated
      with local failure.

PMID- 9241081
TI  - The significant role of telomerase activity in human brain tumors.
AB  - BACKGROUND: In this study, telomerase activity in human brain tumors was
      analyzed. METHODS: Telomerase activity was examined in 41 brain tumor cases (20
      of glioblastoma multiformes [GBMs] [14 primary tumors and 6 recurrent tumors], 3
      anaplastic astrocytomas [AAs], 4 low grade astrocytomas [LGAs] [World Health
      Organization Grade 2], 2 oligodendrogliomas [OGs], 9 meningiomas [MNs], and 3
      metastatic brain tumors [MBTs]) by means of telomeric repeat amplification
      protocol assay. The activity of telomerase was compared with histologic
      diagnosis, the MIB-1 proliferative cell index (PCI), and the patient's prognosis.
      RESULTS: Twelve of 20 GBMs, 2 of 2 OGs, and 3 of 3 MBTs demonstrated telomerase
      activity. AAs, LGAs, and MNs exhibited no activity. No clear correlations were
      confirmed in GBMs between telomerase activity and the MIB-1 PCI data. However,
      the telomerase activity tended to correlate with the patient's prognosis.
      CONCLUSIONS: These results suggest that telomerase activity may be an important
      marker of brain tumor malignancy. Furthermore, the change from negative activity
      to positive activity in the recurrent tumors appeared to be a useful
      prognosticator for malignant astrocytic tumor.

PMID- 9241084
TI  - Supratentorial malignant gliomas in childhood: a single institution perspective.
AB  - BACKGROUND: A retrospective study evaluated the clinical characteristics,
      prognostic factors, and outcome of patients with newly diagnosed supratentorial
      malignant gliomas treated with preirradiation chemotherapy. METHODS: Of 41
      patients with supratentorial malignant gliomas accrued between 1984-1994, all had
      neuroimaging documentation of the extent of resection and 37 had complete
      neuraxis staging prior to treatment; 80% were treated with one of a variety of
      neoadjuvant chemotherapy regimens. RESULTS: Thirteen patients had anaplastic
      astrocytoma (AA), 25 had glioblastoma multiforme (GBM), and 3 had anaplastic
      oligodendroglioma. Gross total resection (GTR) was performed in 10 patients,
      subtotal resection (STR) in 22 patients, and biopsy (Bx) alone in 9 patients. For
      the entire group the 3-year overall and progression free survivals were 35 +/- 8%
      and 18 +/- 6%, respectively. Tumor recurrence was dominantly local. However, 9
      patients with initially local disease failed at a distant neuraxis site, giving a
      26 +/- 7% actuarial risk of dissemination at 3 years. The only significant
      prognostic factor was extent of tumor resection: patients who underwent GTR
      survived longer than those who underwent STR or Bx (P = 0.004). Histology (GBM
      vs. AA), age, and the use of enhanced local dose radiation therapy (brachytherapy
      or stereotactic irradiation) did not affect survival. CONCLUSIONS: Neoadjuvant
      chemotherapy was not associated with a survival rate significantly different from
      that observed in adjuvant chemotherapy studies. Systematic neuraxis staging at
      diagnosis and recurrence revealed a rate of neuraxis dissemination as a component
      of recurrence that was higher than previously reported; the utility of
      craniospinal irradiation in preventing isolated dissemination remains uncertain.

PMID- 9241083
TI  - A dose-intensive, cyclophosphamide-based regimen for the treatment of
      recurrent/progressive or advanced solid tumors of childhood: a report from the
      Australia and New Zealand Children's Cancer Study Group.
AB  - BACKGROUND: Children with solid tumors that progress or recur after conventional
      multimodality therapies have a very poor prognosis. In a pilot study,
      vincristine, etoposide, and dose-escalated cyclophosphamide (VETOPEC) was shown
      to be a promising salvage regimen. Continued accrual of patients and increased
      duration of follow-up has resulted in substantial experience with VETOPEC.
      METHODS: Between May 1991 and March 1994, 56 pediatric patients from 6 centers
      were enrolled in this study; 44 had recurrent or progressive tumors (Group A) and
      12 had newly diagnosed, advanced tumors with a very poor prognosis (Group B). The
      VETOPEC regimen was comprised of vincristine, 0.05 mg/kg, on Days 1 and 14;
      etoposide, 2.5 mg/kg, on Days 1, 2, and 3; and fractionated, dose-escalated
      cyclophosphamide on Days 1, 2, and 3. The initial cyclophosphamide dose was 90
      mg/kg (2.7 g/m2)/cycle with an escalation of 15 mg/kg/cycle in each subsequent
      cycle, to a maximum (over 6 cycles) of 165 mg/kg (5.0 g/m2)/cycle. Tumor response
      was evaluated every two to three cycles and included central review of imaging.
      RESULTS: The combined and partial response rates for Groups A and B were 66% (25
      of 38 patients) and 91% (10 of 11 patients), respectively. In Group A, best
      evaluable responses and event free (EF) survivors were observed with: brain
      tumors (7 of 9 patients; 2 EF at 39 and 45 months [mos], respectively), Wilms'
      tumor (6 of 7 patients; 3 EF at 37-49 mos), and lymphoma (4 of 4 patients; 2 EF
      at 52 and 59 mos, respectively); in Group B best evaluable responses and EF were
      observed with: neuroblastoma (5 of 6 patients; 1 disease free at 57 mos) and
      rhabdomyosarcoma (4 of 4 patients; no survivors). Hematologic toxicity was
      limiting despite support with myeloid growth factors in 33 patients. Four deaths
      in Group A and one in Group B were directly associated with this toxicity.
      Specifically, no cases of drug-related myocardial toxicity or pneumonitis were
      observed. CONCLUSIONS: This chemotherapy regimen with its intense scheduling
      produced a high response rate and appreciable survival in patients with a variety
      of recurrent, progressive, or advanced solid tumors of childhood.

PMID- 9241086
TI  - Surgical treatment of patients with mixed hepatocellular carcinoma and
      cholangiocarcinoma.

PMID- 9241085
TI  - The National Cancer Data Base report on early stage invasive vulvar carcinoma.
      The American College of Surgeons Commission on Cancer and the American Cancer
      Society.
AB  - BACKGROUND: Recent advancement in recommended treatment of early stage vulvar
      carcinoma had emphasized the role of pathologic indications of tumor size and
      lymph node involvement. The purpose of this study was to identify the current
      mode of practice in the management of early stage vulvar carcinoma with primary
      disease limited to the vulva and/or the perineum. METHODS: The National Cancer
      Data Base was accessed to examine vulvar carcinoma cases reported by 1147
      hospitals that had established or were establishing American College of Surgeons
      Commission on Cancer programs. The periods 1988-1989 and 1993-1994 were selected
      for analysis. The analysis was based on the 1553 invasive nonmetastatic
      carcinomas (confined to the vulva and/or the perineum) for which primary lesion
      size and pathologic inguinal lymph node evaluation had been recorded. RESULTS:
      There were no differences in demographic or disease characteristics between 1988
      1989 and 1993-1994. Surgery alone was most often the treatment for lymph node
      negative patients. Radiation therapy was given as an adjunct treatment to 49% of
      patients with positive lymph nodes. Radiation therapy was given fairly equally to
      patients in all lymph node positive categories (1, 2-3, and 4 or more positive
      lymph nodes), with little change between the two time periods. Patients with < or
      = 2 cm lesions were more often treated with conservative surgery. CONCLUSIONS:
      The major diagnostic groups and number of positive lymph nodes were confirmed to
      be prognostically important. Although literature on vulvar disease notes a
      benefit of radiation therapy for patients with more than one positive lymph node,
      radiation therapy was not predictive of survival for patients in this study.

PMID- 9241087
TI  - Influence of methotrexate dose intensity on outcome of patients with high grade
      osteogenic osteosarcoma: analysis of the literature.

PMID- 9241088
TI  - Extramedullary acute promyelocytic leukemia.

PMID- 9241089
TI  - Radiation-associated angiosarcoma: diagnostic and therapeutic implications--two
      case reports and a review of the literature.

PMID- 9241090
TI  - Antimalarial drugs and glucose metabolism.

PMID- 9241091
TI  - Endothelin: from molecule to man.

PMID- 9241092
TI  - The mechanism of the carbamazepine-valproate interaction in humans.
AB  - AIMS: The study investigated the mechanism of the interaction between valproate
      and carbamazepine which causes raised plasma carbamazepine-10,11-epoxide
      concentrations with unchanged plasma carbamazepine concentrations. This
      interaction has usually been attributed to valproate inhibiting epoxide
      hydrolase, the enzyme that catalyses the biotransformation of carbamazepine-10,11
      epoxide to carbamazepine-10,11-trans-diol. METHODS: Clearances of plasma
      carbamazepine, carbamazepine-epoxide and carbamazepine-diol to relevant
      carbamazepine metabolites present in urine were measured under steady-state
      conditions in 17 adults receiving carbamazepine as anticonvulsant monotherapy,
      and in 10 adults taking the drug together with valproate. RESULTS: Plasma
      carbamazepine-epoxide concentrations were higher, relative to carbamazepine dose,
      in the co-medicated patients. Plasma apparent clearances of carbamazepine,
      relative to drug dose, were similar whether or not valproate was taken. Formation
      clearances of carbamazepine-10,11-trans-diol conjugate, and probably of
      carbamazepine-10,11-trans-diol, were lower in subjects co-medicated with
      valproate, and a higher proportion of the carbamazepine dose was excreted in
      urine as carbamazepine-10,11-epoxide. CONCLUSIONS: Valproate appears to inhibit
      the glucuronidation of carbamazepine-10,11-trans-diol, and probably also inhibits
      the conversion of carbamazepine-10,11-epoxide to this trans-diol derivative,
      rather than simply inhibiting the latter reaction only.

PMID- 9241093
TI  - Regional metabolism of articaine in 10 patients undergoing intravenous regional
      anaesthesia during day case surgery.
AB  - AIMS: To study the pharmacokinetics of articaine and its metabolite articainic
      acid, in patients undergoing intravenous regional anaesthesia. METHODS: Ten
      patients (three male, seven female, ASA class 1-2), scheduled for surgery of the
      hand or forearm were included in the study. Articaine (40 ml, 0.5% solution (200
      mg) was injected over 30 s. In total fifteen arterial blood samples were taken;
      one before injection and then at 10 min intervals, starting 10 min after
      completion of injection, until the tourniquet was released; thereafter blood
      samples were drawn at intervals of 1, 5, 10, 15, 20, 25, 30, 45, 60, 75 and 90
      min. The tourniquet was released 30 min after completing the injection. RESULTS:
      During tourniquet application and regional analgesia of 30 min duration, 55% of
      articaine was hydrolysed by plasma (20%) and tissue (35%) esterase activity to
      the metabolite articainic acid. After releasing the tourniquet, articaine and its
      metabolite appeared in the blood; articaine was rapidly eliminated with a t1/2z
      of approximately 60 min. The plasma concentration of the metabolite articainic
      acid was the sum of the amount formed during IVRA (55%) and the amount formed
      after tourniquet release (45%). CONCLUSIONS: Articaine is a safe agent for
      intravenous regional anaesthesia (IVRA) with rapid onset of good surgical
      anaesthesia. During tourniquet application and regional analgesia, 55% of the
      administered dose is already hydrolysed, thus reducing the chance of side effects
      after tourniquet release.

PMID- 9241094
TI  - Improved bioavailability and clinical response in patients with chronic liver
      disease following the administration of a spironolactone: beta-cyclodextrin
      complex.
AB  - AIMS: To compare the absorption and clinical effect of spironolactone from an
      inclusion complex with beta-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in
      chronic liver disease. METHODS: Patients, admitted with chronic liver disease,
      completed a randomized crossover steady state study. They received their
      spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood
      samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid
      balance was recorded on days 5-7 and 12-14. Thirteen (six females) whose mean
      (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study.
      RESULTS: The mean (95% confidence limits) relative bioavailability for SP-COMP
      (compared with ALD) from steady state serum concentrations of canrenone, 6beta
      hydroxyl 7alpha-thiomethyl spironolactone and 7alpha-thiomethyl spironolactone
      was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%,
      respectively. Improvements in clinical status and fluid balance occurred over the
      last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of
      1370(860)ml compared with a gain of 228(936)ml during ALD. CONCLUSIONS: Better
      absorption of spironolactone from the spironolactone: beta-cyclodextrin complex
      formulation should lead to a reduction in dosage and perhaps a more consistent
      effect in patients with chronic liver disease.

PMID- 9241095
TI  - Pharmacodynamics of benserazide assessed by its effects on endogenous and
      exogenous levodopa pharmacokinetics.
AB  - AIMS: The objectives of the study were to investigate the pharmacodynamics of the
      peripheral decarboxylase inhibitor benserazide during multiple-dose regimens.
      METHODS: Two groups of eight healthy male subjects were consecutively treated for
      periods of 14 days with benserazide 5, 25, 100 mg three times daily and 12.5, 50,
      200 mg three times daily, respectively. Plasma levels of levodopa, 3-O-methyldopa
      (3-OMD) and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined before
      benserazide treatment and during all benserazide dosing regimens, as existing
      endogenously and after administration of 250 mg levodopa. RESULTS: Endogenous
      concentrations of levodopa and 3-OMD increased dose-dependently (from 8 up to 52
      microg l(-1) and from 0.02 up to 0.50 mg l(-1) , respectively, at doses of 200
      mg) with ascending doses of benserazide whereas DOPAC levels remained unchanged.
      There were no indications of a plateau in the effects of benserazide on the
      plasma levels of the analytes. The area under the concentration-time curve (AUC)
      of exogenously administered levodopa increased from 1.2 in the control group to
      5.9 mg l(-1) h at benserazide doses of 100-200 mg three times daily. Benserazide
      caused a dose-dependent increase in the AUC of 3-OMD from 7.4 to 106 mg l(-1) h
      at doses of 200 mg. Formation of DOPAC was dose-dependently suppressed, with
      benserazide 5 mg three times daily already halving its AUC. CONCLUSIONS: The
      benserazide-dose response data obtained suggest that even at very high doses
      extracerebral decarboxylase is not yet completely inhibited.

PMID- 9241096
TI  - The comparison of the responsiveness of human isolated internal mammary and
      gastroepiploic arteries to levcromakalim: an alternative approach to the
      management of graft spasm.
AB  - AIMS: We studied the effectiveness of levcromakalim, a potassium channel opener
      (KCO), in the prevention and reversal of spasm in arterial grafts used in
      coronary artery bypass operations, namely, internal mammary artery (IMA) and
      gastroepiploic artery (GEA). METHODS: Spasm was mimicked in vitro in arterial
      rings from 109 patients by increasing the vascular tension with noradrenaline,
      the thromboxane analogue U46619, endothelin-1 and K+. RESULTS: GEA displayed
      considerably higher contractile force to these agents than IMA. Pretreatment with
      levcromakalim depressed significantly the maximal contractile responses (either
      absolute or relative) to noradrenaline and U46619 but did not affect those of
      endothelin-1 and K+ in both of the arteries. Sensitivities (to all agents, except
      to endothelin-1) decreased significantly after levcromakalim. In experiments
      evaluating the antispasmodic activity of levcromakalim, a higher relaxant
      capacity was observed in GEA than IMA (for K+ contraction; IMA: 31.32 +/- 3.83%,
      n= 13 vs GEA: 98.01 +/- 0.71%, n=7, P<0.05). This different activity of
      levcromakalim between two arterial grafts was apparent even when GEA rings were
      contracted to higher force (g) than that of IMA (for K+ contraction; GEA: 72.56
      +/- 4.96%, n = 7). Responses to levcromakalim were similar in IMA and GEA when
      endothelin-1 was used as the spasmogenic agent (IMA: 80.98 +/- 4.85%, n=10 vs
      GEA: 91.93 +/- 3.17%, n=7, P>0.05). CONCLUSIONS: Our results provide evidence
      that levcromakalim may have a therapeutic value in the treatment of spasm of
      coronary artery bypass grafts, especially GEA.

PMID- 9241097
TI  - Haemodynamic effects of adrenomedullin in human resistance and capacitance
      vessels.
AB  - AIMS: The haemodynamic effects of adrenomedullin and calcitonin gene-related
      peptide (CGRP) were studied in resistance and capacitance vessels of healthy
      volunteers. METHODS: Adrenomedullin and CGRP were infused into the brachial
      artery of eight healthy subjects on two separate occasions at doses between 0.3
      30 pmol min(-1). Forearm blood flow was measured using venous occlusion
      plethysmography. Venodilatation to adrenomedullin and CGRP was assessed in a
      further eight subjects by infusing the peptides at doses between 0.3-10 pmol min(
      1) into a dorsal hand vein preconstricted with noradrenaline. Venodilator
      responses were measured as percentage reduction in noradrenaline preconstriction.
      RESULTS: Adrenomedullin and CGRP at a dose of 30 pmol min(-1), produced an
      increase in forearm blood flow of 288 +/- 42% and 252 +/- 30% respectively (mean
      +/- s.e. mean, P<0.001). At doses between 3 and 10 pmol min(-1) adrenomedullin
      was significantly more potent than CGRP. The vasodilatation to both peptides was
      of similar duration with a biological half-life of approximately 18 min.
      Adrenomedullin reversed constriction in dorsal hand veins by 84 +/- 2% (P<0.001)
      at a dose of 10 pmol min(-1). CGRP produced a similar effect reversing
      constriction by 72 +/- 12% at the same dose (P<0.01). In veins, adrenomedullin
      was also more potent than CGRP at doses between 0.3 and 3 pmol min(-1).
      CONCLUSIONS: The lowest dose of adrenomedullin producing significant arteriolar
      dilatation was calculated to produce plasma levels similar to those found in
      heart failure. These findings suggest that in pathophysiological conditions such
      as heart failure circulating levels of adrenomedullin may be within a range
      capable of influencing vascular resistance directly.

PMID- 9241099
TI  - Further evidence that chronic perindopril treatment maintains neurohormonal
      suppression but does not lower blood pressure in chronic cardiac failure.
AB  - AIMS: Previous studies in heart failure (CHF) after temporary diuretic withdrawal
      have suggested that perindopril is associated with no first dose hypotension in
      comparison with other ACE inhibitors (ACEI) or placebo. The aim of this study was
      to explore further the profile of perindopril during chronic dosing. METHODS: We
      report the effects of acute and chronic (8 weeks) treatment with the ACE
      inhibitor perindopril (Per, 2-->4 mg daily) or placebo (P) in a double-blind
      parallel group study of 24 diuretic treated patients (17M; 67 +/- 8 years, 80 +/-
      17 kg) with ischaemic cardiomyopathy (fractional shortening, 19 +/- 5%;
      radionuclide ejection fraction, 31 +/- 3%). Baseline biochemical, hormonal (ACE,
      Ang I, Ang II), isotopic renal function (GFR, ERPF, ECFV), pretreatment diuretic
      dose and heart failure scores were similar between groups. Concomitant cardiac
      treatments remained unchanged and diuretic withdrawal was not used to introduce
      treatment. RESULTS: There were no significant effects on electrolytes, liver
      function tests, serum or erythrocyte magnesium. There was no significant first
      dose fall in SBP over 6 h) (P, baseline 137 +/- 18; min 115 +/- 16 mmHg; Per,
      baseline 137 +/- 15; min 118 +/- 17 mmHg). Neither supine nor erect BP was
      significantly affected by chronic treatment (P, erect baseline 134 +/- 23/76 +/-
      10 to 124 +/- 41/74 +/- 10 mmHg; Per, baseline 135 +/- 21/76 +/- 14 to 128 +/-
      22/70 +/- 12 mmHg, P=NS). Active treatment was associated with significant ACE
      inhibition (P, baseline 47 +/- 17 to 43 +/- 17; Per baseline 49 +/- 15 to 14 +/-
      7); aldosterone (P, baseline 337 +/- 179 to 375 +/- 306; Per, baseline 335 +/-
      357 to 293 +/- 155 pg ml(-1)) and Ang II suppression (P, baseline 9 +/- 9 to 20
      +/- 39; Per baseline 10 +/- 9 to 3 +/- 3 pM). Isotopic renal function was
      unaffected by either treatment. CONCLUSIONS: At this dose (2-4 mg orally) chronic
      perindopril therapy has no significant effect on blood pressure or renal
      function. Sustained neurohormonal suppression of ACE and AII occurred without
      evidence of AII reactivation. A lack of effect on BP at these doses may make
      perindopril suitable for study in unstable patients with acute HF or useful in
      those patients where there are concerns over ACEI induced hypotension.

PMID- 9241098
TI  - Bisoprolol attenuates noradrenaline- and phenylephrine-evoked venoconstriction in
      man in vivo.
AB  - AIMS: The aim of this study was to examine the effects of bisoprolol (BIS), a
      selective beta1-adrenoceptor antagonist without partial agonistic activity, on
      noradrenaline- and phenylephrine-evoked venoconstriction in man using the dorsal
      hand vein compliance technique. METHODS: Twelve healthy male volunteers
      participated in three weekly experimental sessions. Subjects were allocated to
      treatments and sessions on a double-blind basis. In each session either BIS 5 mg
      (BIS5), or BIS 10 mg (BIS10), or placebo was administered orally, and
      noradrenaline acid tartrate (0.1-33.33 ng min (-1) followed by phenylephrine
      hydrochloride (0.033-10 microg min(-l)) was infused into the dorsal hand vein.
      Systolic and diastolic blood pressure and heart rate were also measured. RESULTS:
      Both noradrenaline and phenylephrine produced dose-dependent venoconstriction:
      the geometric mean ED50 for noradrenaline was 3.21 ng min(-1) and for
      phenylephrine 135.04 ng min(-1); the potency ratio (noradrenaline/phenylephrine)
      was 42. Both BIS5 and BIS10 significantly decreased the venoconstriction to
      noradrenaline (ANOVA; P<0.005), and to phenylephrine (ANOVA; P<0.001). The
      antagonism of the venoconstrictor responses was also reflected in a significant
      increase in logED50 values for both noradrenaline (ANOVA; P<0.005), and
      phenylephrine (ANOVA; P<0.0025) in the presence of both doses of BIS. Both doses
      of BIS significantly decreased heart rate (ANOVA; P<0.0001), and systolic blood
      pressure (ANOVA; P<0.0025). CONCLUSIONS: Bisoprolol can antagonize alpha1
      adrenoceptor mediated venoconstriction in the human dorsal hand vein in vivo
      through a mechanism which remains to be elucidated.

PMID- 9241100
TI  - Reduced platelet aggregation after fluvastatin therapy is associated with altered
      platelet lipid composition and drug binding to the platelets.
AB  - AIMS: High plasma cholesterol concentration and increased platelet activity are
      two major risk factors for atherosclerosis. Lovastatin, the lipophilic drug was
      shown to inhibit platelet aggregation whereas pravastatin, the hydrophilic drug
      had no such effect. Analysis of the effect of fluvastatin which is both a
      lipophilic and hydrophilic drug, on platelet aggregation was the goal of the
      present study. METHODS: Fluvastatin 40 mg daily was administered to 25 patients
      with hypercholesterolaemia for up to 24 weeks. Normal subjects acted as controls.
      The influence of fluvastatin on plasma lipids and on platelet aggregation and
      fluidity was studied. The direct effect of fluvastatin on platelets was compared
      with that of other statins. RESULTS: Fluvastatin therapy (40 mg day (-1) for a
      period of 4 weeks) in hypercholesterolaemic patients resulted in a 23% and 29%
      reduction in plasma levels of total cholesterol and LDL-cholesterol respectively.
      Platelet cholesterol/phospholipids molar ratio was reduced by 26% and platelet
      aggregation was significantly (P<0.02) reduced by 10% after 4 weeks of
      fluvastatin treatment. On continuing fluvastatin therapy for additional 20 weeks,
      no further decrement in plasma LDL cholesterol levels or in platelet
      cholesterol/phospholipid ratio were noted. However, platelet aggregation was
      further significantly (P<0.01) reduced by up to 15%. Incubation of platelets with
      increasing concentrations of fluvastatin or lovastatin, demonstrated a dose
      dependent reduction in platelet aggregation, whereas pravastatin showed no
      effect. This inhibitory effect of fluvastatin or lovastatin on platelet
      aggregation (up to 34% or 22% respectively at a concentration of 1 microg statin
      ml (-1) was found both in platelet rich plasma and in washed platelet
      suspensions. Fluvastatin and lovastatin (but not pravastatin), seem to share
      similar platelet binding sites, as non labelled fluvastatin or lovastatin were
      able to displace [3H]-labeled-fluvastatin from its binding sites on platelets.
      CONCLUSIONS: Fluvastatin therapy reduces platelet aggregation via a dual effect
      which involves its in vivo hypocholesterolaemic action on platelet cholesterol
      content, and also a direct effect of the drug binding to the platelets. The
      antiatherogenicity of fluvastatin may be related, in addition to its plasma
      cholesterol lowering ability, to its inhibitory effect on platelet activation.

PMID- 9241101
TI  - Consumption of non-steroidal anti-inflammatory drugs and the development of
      functional renal impairment in elderly subjects. Results of a case-control study.
AB  - AIMS: The aim of the present study was to explore the level of risk associated
      with community use of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: We
      carried out a matched case-control study of the relationship between recent use
      of NSAIDs and the presence of functional renal impairment present at the time of
      hospitalisation with a range of clinical problems. Cases (n = 110) were
      consecutive patients admitted acutely to hospital who had serum creatinine levels
      greater than or equal to 0.15 mmol l(-1) , which improved by 20% or more within
      the next 14 days, or prior to discharge from hospital. Controls (n= 189) were
      subjects of the same sex and age (to within 5 years) as the cases, who were
      admitted to the same hospital, who had normal serum creatinine levels (<0.12 mmol
      l(-1) throughout their hospital stay. Information on a number of study factors,
      including recent use of aspirin and other NSAIDs, was obtained by structured
      interview. RESULTS: Overall, there was a weak association between consumption of
      NSAIDs (including non-prophylactic aspirin) and the development of functional
      renal impairment-adjusted odds ratios (OR) with use of NSAIDs in the previous
      week or in the previous month: OR 1.5 (95% CI 0.80, 2.9) and 1.8 (95% CI 0.97,
      3.4) respectively. In subjects with a previous history of renal disease the
      adjusted OR was 6.6 (0.75, 57.8) and in those with a history of gout or
      hyperuricaemia the OR was 7.2 (1.3, 40.2). There was a weak positive relationship
      between the dose of drug consumed in the previous week and the odds of functional
      renal impairment. The relationship between risk and published figures for drug
      half-lives (t1/2) was stronger. The odds ratio increased from 1.2 (95% CI 0.61,
      2.4) with a t1/2 < or = 4 h, to 4.8 (1.5, 15.8) with a t1/2 of < or = 12 h
      (P=0.012, test for trend). This relationship remained statistically significant
      after adjustment for a number of clinical variables and the dose of drug
      ingested. CONCLUSIONS: NSAIDs are an important cause of functional renal
      impairment in subjects with renal disease or a history of gout or hyperuricemia.
      The half-life of the drug is more important than the ingested dose in determining
      the risk of this outcome. Long half-life drugs should be avoided in individuals
      who are at risk of developing renal impairment.

PMID- 9241102
TI  - Single-dose pharmacokinetics of felbamate in patients with renal dysfunction.
AB  - AIMS: The purpose of this study was to evaluate the effects of renal impairment
      on the single-dose pharmacokinetics of the antiepileptic felbamate. METHODS:
      Twelve subjects with three levels of renal dysfunction (creatinine clearance > 30
      80, > 10-30 or 5-10 m min(-1)) and four controls with normal renal function
      (creatinine clearance > 80 ml min(-1) were studied). Plasma and urine samples
      were obtained for 144 h following administration of a single 1200 mg dose.
      RESULTS: Compared with controls, apparent total body clearance, renal clearance
      and urinary excretion of felbamate were decreased, and half-life, Cmax and AUC
      values were increased in subjects with renal dysfunction. The magnitude of these
      changes was associated with the degree of renal dysfunction. Nonrenal clearance
      and apparent volume of distribution values were also lower in renal dysfunction
      subjects, but there was no association between the extent of these changes and
      degree of renal dysfunction. Renal clearance of felbamate accounted for
      approximately 30% of apparent total body clearance in the control group and from
      9-22% in the renal failure patients. Renal clearance of felbamate was
      significantly correlated with creatinine clearance (r = 0.75; P< 0.001).
      CONCLUSIONS: These data suggest that initial dosage and titration of felbamate
      may require adjustment in patients with renal dysfunction.

PMID- 9241104
TI  - Reporting of adverse drug reactions by hospital doctors and the response to
      intervention.
AB  - AIMS: In Ireland there are relatively fewer adverse drug reaction (ADR/yellow
      card) reports from doctors in hospital than in general practice. The aim of this
      study was to review the attitudes to reporting of ADRs of hospital doctors and to
      determine the effect of making yellow cards freely available. METHODS: A postal
      survey of actively practising doctors with follow-up of nonresponders was
      undertaken. We addressed the single most frequently claimed deterrent to
      reporting, unavailability of yellow cards, by making cards prominently available
      and placing one in patient's chart upon admission. In addition, doctors were
      regularly reminded that ADRs should be reported. RESULTS: Of 118 hospital based
      doctors, only 45% had ever reported an ADR. Fewer than 5% of pre-registration
      house officers had reported an ADR and the likelihood of reporting increased with
      seniority and was greater among physicians than surgeons. We found no evidence
      that doctors had published case reports in place of submitting ADR reports. Over
      3 months, the greater availability of yellow cards and reminders about reporting
      ADRs led to an approximate five-fold increase in reports but reporting declined
      rapidly thereafter when verbal reminders were withdrawn, despite continued ready
      availability of cards suggesting that making cards available alone does not
      significantly increase reporting. CONCLUSIONS: This study indicates there may be
      more fundamental constraints to reporting than attitudinal surveys would suggest
      and we need to explore additional avenues to ensure a 'reporting culture'.

PMID- 9241103
TI  - The effect of pharmacological supplementation with vitamin C on low-density
      lipoprotein oxidation.
AB  - AIMS: Vitamin C (ascorbic acid) is a powerful antioxidant but there is limited
      information on its ability to prevent LDL oxidation and its interaction with
      other natural antioxidants in vivo. We assessed the effect of 4 weeks
      pharmacological supplementation with vitamin C 1 g day(-1) on copper induced LDL
      oxidation and lipid peroxidation. METHODS: Blood samples were obtained at
      baseline and at the end of 4 weeks supplementation from 11 healthy non-smokers
      and also from nine control subjects. Plasma lipid peroxides were measured as
      malondialdehyde (MDA) by h.p.l.c. The relationship between vitamin C and two
      other important antioxidants, vitamin E and glutathione, was also studied.
      RESULTS: There was no difference in baseline values between the two groups and
      the oxidizability of LDL, assessed as the lag phase of conjugated dienes
      production and the formation of thiobarbituric acid reactive substances (TBARS),
      remained unchanged after 4 weeks. In the vitamin C supplemented group only, there
      was a 2.2-fold increase in plasma ascorbic acid level and a 28% increase in red
      cell reduced glutathione (GSH) (P<0.001). Vitamin E, measured as alpha
      tocopherol, in red cells increased significantly (P<0.02) and plasma MDA was
      reduced (P<0.01). CONCLUSIONS: Vitamin C did not alter LDL oxidation but it may
      have a protective role against lipid peroxidation as shown by decreased plasma
      MDA levels and enhanced vitamin E and GSH status.

PMID- 9241105
TI  - Clinical pharmacology and therapeutics--past, present and future.
AB  - AIMS: To obtain information about the speciality of clinical pharmacology and
      therapeutics in the United Kingdom. METHODS: A survey of the views of 26
      individuals in academic posts in clinical pharmacology and therapeutics was
      carried out by postal questionnaire. Response rate was 100%. RESULTS: Of 25
      assessable responses of 25 centres, there were 35 academic staff of professorial
      status (median 2, range 0-5) and 61 staff of reader/senior lecturer status
      (median 2, range 0-5) but only 20 clinical staff in training grades in 19
      institutions. All had extensive clinical commitments. Two-thirds of respondents
      considered that the speciality was stable locally and nationally. However,
      recruitment of trainees was poor with only 8% of responders having several good
      applicants for each post and 90% reported that recruitment had deteriorated in
      the last 5-10 years. Likely good future careers for clinical pharmacologists in
      training were considered by 75-80% of respondents to likely lie in the
      pharmaceutical industry or regulatory authorities. Greater flexibility is
      required to facilitate training in clinical pharmacology and therapeutics.
      CONCLUSIONS: Clinical pharmacology and therapeutics in the United Kingdom has a
      strong academic base but a sub-optimal age structure. Recent experience in
      recruitment into training posts was disappointing. This may reflect wider
      problems of recruitment into academic medicine in this country.

PMID- 9241106
TI  - Spontaneous reports of psychiatric adverse effects to mefloquine in the
      Netherlands.

PMID- 9241107
TI  - Effects of HIV-1 on the surface expression of LFA-1 on cultured monocytes.
AB  - CD11a, the alpha chain of LFA-1, which is a member of the LeuCAM family of
      integrins, has been implicated in the formation of HIV-induced syncytia and may
      contribute to the depletion of CD4-positive lymphocytes seen in patients with HIV
      infection. In this study, we examined the effects of HIV-1 infection on the
      expression of CD11a on cultured monocyte-derived macrophages (MDMs). Monocytes
      isolated from peripheral blood and maintained in suspension culture were infected
      in vitro with a monocytotropic variant of HIV-1 (Ba-L). Surface expression of
      CD11a, measured by indirect immunofluorescence and flow cytometry, was
      significantly higher on HIV-infected cells than on mock-infected cells from the
      same donor. Upregulation of CD11a expression was unaffected by the HIV reverse
      transcriptase inhibitor, zidovudine, indicating that it did not depend on reverse
      transcription. A step before reverse transcription, such as viral binding,
      appears sufficient to trigger an increase in CD11a expression. This hypothesis is
      supported by our findings of soluble recombinant CD4 inhibition of HIV-induced
      CD11a upregulation. It is possible that induction of a cytokine network by HIV
      underlies this effect, given our findings that exposure of uninfected MDMs to
      granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically increased
      CD11a expression and that HIV-infected MDMs secreted more GM-CSF than mock
      infected cells.

PMID- 9241108
TI  - Meta-analysis of prophylactic treatments against Pneumocystis carinii pneumonia
      and toxoplasma encephalitis in HIV-infected patients.
AB  - In a meta-analysis, we examined the efficacy of aerosolized pentamidine,
      trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the
      prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in
      patients with HIV infection. Of 22 trials, 13 compared trimethoprim
      sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in
      combination with pyrimethamine with aerosolized pentamidine, and eight compared
      trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients
      were treated with trimethoprim-sulfamethoxazole, 1548 patients with
      dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine.
      For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P.
      carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for
      toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim
      sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii
      pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was
      0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus
      dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI,
      0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04).
      Although current evidence does not allow a definitive recommendation,
      administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii
      pneumonia and toxoplasmosis in patients with HIV infection is consistent with the
      available data.

PMID- 9241109
TI  - Determinants of complementary therapy use in HIV-infected individuals receiving
      antiretroviral or anti-opportunistic agents.
AB  - OBJECTIVE: To identify sociodemographic and clinical characteristics of persons
      using complementary therapy in an HIV/AIDS drug treatment program and to evaluate
      the associations between complementary therapy use and participant
      characteristics. METHODS: A cross-sectional study using program participants who
      completed an annual participant survey between 09/95 and 06/96. Surveys gathered
      data on use and motivations for use of complementary therapies. Complementary
      therapies included dietary, medicinal, tactile, and relaxation therapies.
      Statistical analyses were carried out using parametric and nonparametric measures
      and multivariate logistic analyses. Multivariate modeling considered age, income,
      education, time spent out of bed, and degree of pain as independent variables
      against complementary therapy use (Yes versus No). All reported p values are two
      sided. RESULTS: A total of 657 participants completed an annual participant
      survey within the study period. Of these, 256 participants (39%) had ever used
      complementary therapies. Univariate analysis indicated that 195 patients (30%)
      had used dietary supplements, 141 (22%) had used herbal and other medicinal
      therapies, 145 (22%) had used tactile therapies, and 128 (20%) had used mental
      relaxation techniques. Multivariate analysis indicated that complementary use was
      independently associated with younger median age (p = .003), income >$7,300 U.S.
      (p = .014), having greater physical pain (p = .003), and a university education
      (p = .002). CONCLUSION: Use of complementary therapies in conjunction with
      HIV/AIDS medications appears to be most prevalent in young and highly educated
      individuals and to be associated with the debilitating and chronic nature of HIV
      disease.

PMID- 9241110
TI  - HIV-1 RNA detection in plasma for the diagnosis of infection in neonates. The
      French Pediatric HIV Infection Study Group.
AB  - The objective of this study was to assess the frequency of detection of HIV-1 RNA
      in plasma of neonates born to HIV-1-seropositive mothers and to determine the
      diagnostic value of this method in the neonatal period. The study involved 96
      infants among those enrolled in the French National Prospective Study. HIV-1 RNA
      was detected in the first 10 days of life by nucleic acid sequence-based
      amplification (NASBA) in 12 of 48 plasma samples of infected infants and in 39 of
      39 of the second samples taken before the age of 3 months. On the same samples,
      peripheral blood mononuclear cell (PBMC) DNA polymerase chain reaction (PCR) or
      viral culture that had been routinely performed were found to be positive in 11
      of 48 samples taken in the first 10 days of life and 39 of 39 second samples. For
      the noninfected infants, HIV-1 RNA was never detected in the 48 samples taken in
      the first 10 days of life and was detected in one of the 48 samples taken before
      the age of 3 months. HIV-1 RNA detection in plasma by NASBA has sensitivity and
      specificity equal to those of DNA PCR and culture on PBMC for the diagnosis of
      infection in infants with the clade B virus. This standardized method gives rapid
      results on a small volume of plasma and seems well suited for diagnosis on a
      large scale.

PMID- 9241111
TI  - Compliance with voluntary prenatal HIV testing in a large health maintenance
      organization (HMO).
AB  - Results of a recent national clinical trial show that maternal-to-fetal transfer
      of HIV can be decreased threefold by prenatal, intrapartum, and neonatal
      treatment. The question is whether to make prenatal HIV testing compulsory or to
      encourage voluntary testing. Kaiser Permanente Northern California (KPNC), which
      has 2.5 million members, is part of a large health maintenance organization
      (HMO). In 1994, KPNC cared for 32,700 prenatal patients; 16,500 (50%) agreed to
      voluntary HIV testing. Compliance with testing ranged from 0% to 92% among the 31
      KPNC locations. A study done by telephone survey identified three main factors
      favoring success of voluntary HIV screening: the ease and accessibility of HIV
      testing, a designated educator, and the presence of a registered nurse on the
      counseling team. In 1995, following feedback to the 31 facilities of the 1994
      results, compliance rose to 19,800 of 31,300 prenatal patients (63%). KPNC, by
      encouraging counseled voluntary screening and following known positive cases,
      hopes to identify, track, and offer treatment options to all HIV-positive
      prenatal patients.

PMID- 9241112
TI  - Penetration of 3'-amino-3'-deoxythymidine, a cytotoxic metabolite of zidovudine,
      into the cerebrospinal fluid of HIV-1-infected patients.
AB  - The penetration of 3'-amino-3'-deoxythymidine (AMT) into the cerebrospinal fluid
      (CSF) of HIV-1-infected patients has been investigated. In 23 patients who used
      zidovudine (ZDV) chronically, CSF and plasma samples were assayed for AMT and
      ZDV. The influences of time between ZDV oral administration and lumbar puncture,
      of ZDV dose, and of the medical indication for lumbar puncture based on the
      concentration of AMT in CSF and on the CSF-plasma concentration ratio were
      investigated. AMT can be detected in the CSF after oral administration of ZDV;
      concentrations of AMT in CSF ranged from 0.75 to 4.8 ng/ml (median, 1.7 ng/ml).
      The median CSF-plasma concentration ratio was 1, and equaled that for ZDV. CSF
      and plasma concentrations of AMT were approximately threefold higher in patients
      with cerebral toxoplasmosis; the CSF-plasma concentration ratio remained equal to
      unity in these cases. This phenomenon might be caused by a pharmacokinetic
      interaction between AMT and pyrimethamine, sulfadiazine, folinic acid, or a
      combination of these. The clinical relevance of AMT, especially the possibility
      of decreased efficacy of ZDV, throughout the body and in the central nervous
      system, and the involvement of this metabolite in ZDV-induced myelosuppression,
      remains to be established.

PMID- 9241114
TI  - Comparative rates of disease progression among persons infected with the same or
      different HIV-1 strains. The Transfusion Safety Study Group.
AB  - Rates of HIV-1 progression vary widely. To investigate the relative effects of
      viral and host characteristics on course, we compared persons infected by the
      same and different subtype B strains. Forty-three infection chain clusters were
      identified, each defined by an infected blood donor, that donor's recipients, and
      the recipients' sexual partners, representing second and third generations of
      infection. Analysis of levels and rates of change in CD4 lymphocyte counts and
      viral load showed that members within a cluster were no more alike in their rates
      of change in CD4+ lymphocyte counts or viral RNA levels than among clusters.
      Differences in entry viral RNA levels by cluster were marginal and markedly
      smaller than interindividual differences. These results argue that, in general,
      host factors outweigh differences in viral strain in determining HIV-1 disease
      progression.

PMID- 9241113
TI  - Growth hormone secretion in HIV-positive versus HIV-negative hemophilic males
      with abnormal growth and pubertal development. The Hemophilia Growth and
      Development Study.
AB  - Growth and pubertal development in hemophilic males, age 6-19 years at baseline,
      were evaluated over a 3.5-year period in 207 HIV-positive and 126 HIV-negative
      subjects as part of the Hemophilia Growth and Development Study. METHODS: Thyroid
      function, insulin-like growth factor I (IGF-1) levels, bone age, cranial magnetic
      resonance image normality, CD4+ counts, and serum testosterone levels of study
      participants were measured at baseline. An extensive endocrine evaluation was
      performed in subjects who demonstrated declines in height for age (measurement
      <5th percentile with two pervious heights >10th percentile), who had not achieved
      Tanner stage 4 level of pubertal development by age 15 years or who had abnormal
      growth velocity, which included assessment of peak stimulated growth hormone
      response after clonidine stimulation, 12-hour growth hormone profiles, and serum
      beta carotene levels (triggered protocol). RESULTS: For almost the entire group (
      99%), thyroid function tests were normal for age. IGF-1 levels were normal for
      93% of the cohort. A total of 120 subjects, 89 HIV-positive and 31 HIV-negative,
      had an abnormality of growth, pubertal development, or both; 34 (11.1%) HIV
      positive and 4 (3.6%) HIV-negative subjects had declines in height (p = .001), 20
      (23.3%) HIV-positive and 5 (15.8%) HIV-negative subjects had not achieved Tanner
      stage 4 by 15 years of age (p = .372) and 59 (43.4%) HIV-positive and 23 (25.6)
      HIV-negative subjects had abnormal growth velocity (p < 0.001). Among subjects
      with abnormal height or growth velocity, the HIV-positive group had significantly
      lower mean age-adjusted testosterone levels than did the HIV-negative group (p =
      .030). Within the HIV-positive group, older subjects with abnormal height or
      growth velocity had significantly lower mean bone age than subjects of similar
      age without growth abnormalities (p = .0092). Extensive testing was done in 39
      patients (32 HIV-positive, 7 HIV-negative). Half of the HIV-positive subjects had
      mean 12-hour growth hormone levels <3 ng/ml, 47% had peak stimulated levels <10
      ng/ml, 28% had peak spontaneous values <10 ng/ml, and 38% had low levels of IGF
      1. In the HIV-positive cohort, there was no difference in the rate of
      abnormalities of growth hormone secretion between those with CD4+ counts > or =
      or <200 cells/mm3 and between those subjects that met the 1987 Centers for
      Disease Control (CDC) surveillance definition of AIDS. In the subset of HIV
      positive patients with abnormal peak growth hormone levels after clonidine
      stimulation, growth hormone response correlated positively with CD4+ count (r =
      .657, p = .0056) and beta carotene concentration (R = .596, p = .0192).
      CONCLUSIONS: The results of this longitudinal study suggest that abnormalities of
      growth and pubertal development, particularly an abnormal growth velocity, are
      common in HIV-infected hemophilic boys and adolescents. These abnormalities might
      serve as indicators of the presence of HIV infection in this at-risk population.
      Since thyroid function tests and IGF-1 levels were normal, the etiology of growth
      impairment in HIV infection does not appear to be secondary to inadequate caloric
      intake or acquisition, or severe illness such as that caused by recurrent or
      persistent infection. Rather, HIV infection appears to lead to diminished growth
      hormone production or release and decreased androgen secretion, even before the
      development of AIDS and immunocompromise. These results provide a rationale for
      trials of treatment with growth hormone or androgens in patients with
      abnormalities of endocrine function.

PMID- 9241115
TI  - Trends in HIV counseling and testing of clients attending a public sexually
      transmitted disease clinic in Portland, Oregon, 1989-1995.
AB  - To assess the trend in acceptance of human immunodeficiency virus counseling and
      testing (HIV-CT) among clients attending a public sexually transmitted disease
      (STD) clinic, 13,139 clients who visited the largest STD clinic in Oregon at
      least once from 1989 through 1995 were investigated. Overall, 6236 (47.5%) of the
      clients accepted HIV-CT, and 98 (0.7%) clients reported having previously tested
      positive for HIV infection. The proportion of clients accepting HIV-CT increased
      from 28.2% in 1989 to 60.1% in 1995 (trend: p < 0.001). Among those who had never
      tested for HIV, acceptance of HIV-CT increased from 28.4% in 1989 to 60.9% in
      1995 among HIV-uninfected clients (trend: p < 0.001) and from 20.6% in 1989 to
      43.8% in 1995 among HIV-infected clients (trend: p = 0.13). The proportion
      increased from 25.9% in 1989 to 59.4% in 1995 (trend: p < 0.001) among those who
      previously tested negative for HIV and from 8.3% in 1989 to 25.0% in 1995 (trend:
      p = 0.03) among those who previously tested positive for HIV. Increases were seen
      in both sexes across all age and racial or ethnic groups. Acceptance of HIV
      testing increased among gay or bisexual men from 29% in 1989 to 57% in 1995
      (trend: p < 0.001), and among IDUs from 49.5% to 78.8% (trend: p < 0.001). We
      conclude that HIV-CT is becoming more acceptable among public STD clinic clients,
      although extra efforts must be made to reach the clients who know they carry the
      virus but continue to practice unsafe sex.

PMID- 9241116
TI  - Who uses needle exchange? A study of injection drug users in treatment in San
      Francisco, 1989-1990.
AB  - We examined use of the San Francisco needle exchange program (NEP) by 1093
      injection drug users (IDUs) recruited in methadone maintenance and out-patient
      detoxification programs in the first 2 years after the opening of the NEP in
      1988. Thirty-one percent of IDUs had ever used the NEP. IDUs who were frequent
      injectors, homeless, and aware of their serostatus were more likely to use the
      NEP. To assess self-selection of IDUs at risk for seroconversion for using needle
      exchange, we calculated pre-needle exchange seroconversion rates. Among 385 IDUs
      seen twice, the HIV seroconversion rate was 0.38% per person year among subjects
      who never used needle exchange, but it was 9.34% per person year among those who
      later used needle exchange (p = 0.003). NEP attracted a subset of IDUs at very
      high risk for HIV infection. Among injectors who were interviewed before and
      after the opening of the needle exchanges in San Francisco, the number of sharing
      partners did not change among IDUs who attended or among IDUs who never attended
      the NEP. The NEP attracted a very-high-risk subgroup of IDUs, as measured by risk
      behavior and pre-needle exchange HIV-seroconversion rate. NEPs should be
      considered prime sites for behavior-change interventions.

PMID- 9241117
TI  - Willingness to participate in HIV-1 vaccine efficacy trials and the effect of
      media events among gay and bisexual men in New York City: Project ACHIEVE.
AB  - Efficacy trials of candidate HIV-1 vaccines require study populations at high
      risk of infection who adhere to study protocols and who are willing to
      participate. Data from HIV-1 antibody-negative men (n = 698) enrolled in Project
      ACHIEVE in New York City were analyzed to assess willingness to participate in
      efficacy trials, factors influencing willingness, and the effect on willingness
      of the June 1994 media events about the decision not to proceed with phase III
      trials and about breakthrough infections during phase I and II vaccine trials.
      Sixty-eight percent indicated they would definitely or probably be willing to
      participate. Men enrolled during the time of media events were significantly less
      willing compared with men enrolled during other periods. These men were also more
      likely to mention safety of the vaccine, fear or mistrust of research or
      government, and social risks as important factors in their decision compared with
      men enrolled during other periods. The most frequently cited motivator for
      participation was altruism (57%); the most frequently cited barriers were vaccine
      safety (36%) and vaccine-induced seropositivity (19%). A substantial proportion
      of this cohort was willing to participate in future vaccine efficacy trials.
      However, because willingness may be affected by issues of vaccine safety, vaccine
      induced seropositivity, and media coverage of these issues, significant efforts
      are needed for participant and community education, and specific concerns must be
      addressed in the design and implementation of trials.

PMID- 9241118
TI  - HIV-specific cytotoxic T lymphocytes in persons exposed through sexual contact
      with HIV-infected patients.

PMID- 9241119
TI  - Effect of HIV-1 genetic diversity on HIV-1 RNA quantification in plasma:
      comparative evaluation of three commercial assays.

PMID- 9241120
TI  - Mycobacterial acute lumbosacral polyradiculopathy as the initial manifestation of
      AIDS.

PMID- 9241121
TI  - CD8 T-cell response to antiretroviral therapy.

PMID- 9241122
TI  - Risk factors for HIV-1 infection among pregnant women in French Guiana.

PMID- 9241123
TI  - Use of protease inhibitors among persons with AIDS in Los Angeles County.

PMID- 9241124
TI  - Nonatopic asthma: in vivo airway hyperreactivity adoptively transferred to naive
      mice by THY-1(+) and B220(+) antigen-specific cells that lack surface expression
      of CD3.
AB  - To investigate the cellular immune events contributing to airway hyperreactivity
      (AHR), we studied an in vivo mouse model induced by the hapten picryl
      (trinitrophenyl) chloride (PCl). Mice were immunized by cutaneous contact
      sensitization with PCl and airway challenged subsequently with picryl sulfonic
      acid (PSA) antigen (Ag). Increased airway resistance was produced late (24 h)
      after Ag challenge, disappeared by 48 h, and was associated with no decrease in
      diffusion capacity. AHR could be produced in PCl immune/ PSA challenged mice on
      day 7 or even, with challenge, as early as 1 d after contact sensitization, after
      adoptive transfer of immune cells lacking CD3(+) contact sensitivity effector T
      cells, or after transfer of Ag-specific lymphoid cells depleted of conventional T
      lymphocytes with surface determinants for CD3, CD4, CD8, TCR-beta, or TCR-delta
      molecules. Further experiments showed that development of AHR depended upon
      transfer of immune cells expressing surface membrane Thy-1 and B220 (CD45RA)
      determinants. We concluded that a novel population of Ag-specific lymphoid cells
      with a defined surface phenotype (Thy-1(+), CD3(-), CD4(-), CD8(-), TCR-alphabeta
      , TCR-gammadelta-, and CD45RA+) is required in a mouse model for the development
      of AHR.

PMID- 9241125
TI  - Probucol and multivitamins in the prevention of restenosis after coronary
      angioplasty. Multivitamins and Probucol Study Group.
AB  - BACKGROUND: Oxidizing metabolites generated at the site of coronary angioplasty
      can induce chain reactions that may lead to restenosis. Antioxidants may counter
      oxidative stress and modify neointimal formation and vascular remodeling.
      Experimental data and small clinical studies have suggested that antioxidants may
      prevent restenosis after angioplasty. In a double-blind, randomized trial, we
      studied whether drugs with antioxidant properties decrease the incidence and
      severity of restenosis after angioplasty. METHODS: One month before angioplasty,
      317 patients were randomly assigned to receive one of four treatments: placebo,
      probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin
      C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice
      daily. Patients were treated for four weeks before and six months after
      angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin
      E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according
      to their treatment assignments. Base-line and follow-up angiograms were
      interpreted by blinded investigators using a quantitative approach. RESULTS: The
      mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12
      +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment
      group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the
      placebo group (P = 0.006 for those receiving vs. those not receiving probucol,
      and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis
      rates per segment were 20.7 percent in the probucol group, 28.9 percent in the
      combined-treatment group, 40.3 percent in the multivitamin group, and 38.9
      percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates
      of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6
      percent, respectively (P = 0.009 for probucol vs. no probucol). CONCLUSIONS: The
      antioxidant probucol is effective in reducing the rate of restenosis after
      balloon coronary angioplasty.

PMID- 9241126
TI  - Outcome of cord-blood transplantation from related and unrelated donors. Eurocord
      Transplant Group and the European Blood and Marrow Transplantation Group.
AB  - BACKGROUND: Cord-blood banks have increased the use of cord-blood transplantation
      in patients with hematologic disorders. We have established a registry containing
      information on the outcome of cord-blood transplantation. METHODS: We sent
      questionnaires to 45 transplantation centers for information on patients
      receiving cord-blood transplants from 1988 to 1996. Reports on 143
      transplantations, performed at 45 centers, were studied, and the responses were
      analyzed separately according to whether the donor was related or unrelated to
      the recipient. RESULTS: Among 78 recipients of cord blood from related donors,
      the Kaplan-Meier estimate of survival at one year was 63 percent. Younger age,
      lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative
      serologic results in the recipient were favorable prognostic factors. Graft
      versus-host-disease of at least grade II occurred at estimated rates of 9 percent
      in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA
      mismatched cord blood. Neutrophil engraftment was associated with an age of less
      than six years (P = 0.02) and a weight of less than 20 kg (P = 0.02), and it
      occurred in 85 percent of patients receiving 37 million or more nucleated cells
      per kilogram of body weight. Among 65 patients who received cord blood from
      unrelated donors, the Kaplan-Meier estimate of survival at one year was 29
      percent. Cytomegalovirus-negative serologic status in these recipients was
      associated with improved survival (P = 0.03) and was the most important predictor
      of graft-versus-host disease (P = 0.04). Neutrophil recovery occurred in 94
      percent of the patients who received 37 million or more nucleated cells per
      kilogram from unrelated donors. CONCLUSIONS: Cord blood is a feasible alternative
      source of hematopoietic stem cells for pediatric and some adult patients with
      major hematologic disorders, particularly if the donor and the recipient are
      related.

PMID- 9241128
TI  - Surveillance for Escherichia coli O157:H7 infections in Minnesota by molecular
      subtyping.
AB  - BACKGROUND: Escherichia coli O157:H7 is a leading cause of diarrhea and the
      hemolytic-uremic syndrome. Current public health surveillance for E. coli O157:H7
      requires considerable resources; traditional methods lack the sensitivity and
      specificity to detect outbreaks effectively. METHODS: During 1994 and 1995, the
      Minnesota Department of Health requested that all clinical isolates of E. coli
      O157:H7 be submitted to our laboratory. Isolates were subtyped by pulsed-field
      gel electrophoresis (PFGE), and patients were interviewed about potential sources
      of infection. RESULTS: In 1994 and 1995, 344 cases of E. coli O157:H7 infection
      were reported to the Minnesota Department of Health; 317 (92 percent) were
      subtyped by PFGE, and 143 distinct PFGE patterns were identified. Ten outbreaks
      of E. coli O157:H7 were identified; these accounted for 56 (18 percent) of the
      317 subtyped cases. Four outbreaks were detected solely as a result of subtype
      specific surveillance. In 11 two-week periods, the number of reported cases of E.
      coli O157:H7 doubled from the previous two weeks. In eight of these instances,
      the patterns identified were dissimilar and there were no outbreaks. Two of the
      remaining three increases resulted from multiple simultaneous outbreaks.
      CONCLUSIONS: Subtype-specific surveillance for E. coli O157:H7 can identify
      outbreaks that are not detected by traditional methods and can ascertain whether
      sudden increases in reported cases are due to sporadic isolated cases or to one
      or more outbreaks.

PMID- 9241127
TI  - Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis.
AB  - BACKGROUND AND METHODS: Osteoporosis is a recognized complication of
      corticosteroid therapy. Whether it can be prevented is not known. We conducted a
      12-month, randomized, placebo-controlled study of intermittent etidronate (400 mg
      per day for 14 days) followed by calcium (500 mg per day for 76 days), given for
      four cycles, in 141 men and women (age, 19 to 87 years) who had recently begun
      high-dose corticosteroid therapy. The primary outcome measure was the difference
      in the change in the bone density of the lumbar spine between the groups from
      base line to week 52. Secondary measures included changes in the bone density of
      the femoral neck, trochanter, and radius and the rate of new vertebral fractures.
      RESULTS: The mean (+/-SE) bone density of the lumbar spine and trochanter in the
      etidronate group increased 0.61 +/- 0.54 and 1.46 +/- 0.67 percent, respectively,
      as compared with decreases of 3.23 +/- 0.60 and 2.74 +/- 0.66 percent,
      respectively, in the placebo group. The mean differences between the groups after
      one year were 3.72 +/- 0.88 percentage points for the lumbar spine (P = 0.02) and
      4.14 +/- 0.94 percentage points for the trochanter (P = 0.02). The changes in the
      femoral neck and the radius were not significantly different between the groups.
      There was an 85 percent reduction in the proportion of postmenopausal woman with
      new vertebral fractures in the etidronate group as compared with the placebo
      group (1 of 31 patients vs. 7 of 32 patients, P = 0.05), and the etidronate
      treated postmenopausal women also had significantly fewer vertebral fractures per
      patient (P = 0.04). CONCLUSIONS: Intermittent etidronate therapy prevents the
      loss of vertebral and trochanteric bone in corticosteroid-treated patients.

PMID- 9241129
TI  - Images in clinical medicine. Cerebral venous thrombosis.

PMID- 9241130
TI  - Obesity.

PMID- 9241131
TI  - Antioxidants and atherosclerotic heart disease.
AB  - Epidemiologic studies have provided evidence of an inverse relation between
      coronary artery disease and antioxidant intake, and vitamin E supplementation in
      particular. The oxidative-modification hypothesis implies that reduced
      atherosclerosis is a result of the production of LDL that is resistant to
      oxidation, but linking the reduced oxidation of LDL to a reduction in
      atherosclerosis has been problematic. Several important additional mechanisms may
      underlie the role of antioxidants in preventing the clinical manifestations of
      coronary artery disease (Fig. 2). Specifically, there is evidence that plaque
      stability, vasomotor function, and the tendency to thrombosis are subject to
      modification by specific antioxidants. For example, cellular antioxidants inhibit
      monocyte adhesion, protect against the cytotoxic effects of oxidized LDL, and
      inhibit platelet activation. Furthermore, cellular antioxidants protect against
      the endothelial dysfunction associated with atherosclerosis by preserving
      endothelium-derived nitric oxide activity. We speculate that these mechanisms
      have an important role in the benefits of antioxidants.

PMID- 9241132
TI  - Restenosis revisited--new targets, new therapies.

PMID- 9241133
TI  - Preventing glucocorticoid-induced osteoporosis.

PMID- 9241134
TI  - Reefer madness--the federal response to California's medical-marijuana law.

PMID- 9241136
TI  - Studies of Ternary Surface Complexes at Liquid-Solid Interfaces in Seawater
AB  - The E (%)-pH curves of the ternary surface complexes at liquid-solid interfaces
      in the simulated seawater system of alpha-FeOOH-Cu(II)-tryptophan were
      determined. The diffuse reflectance IR spectra of the species at the solid
      surfaces in the above ternary equilibration system were examined. The above two
      results were comparatively studied. It is shown that the coadsorption of Cu(II)
      and tryptophan on alpha-FeOOH surface results in the formation of the ternary
      surface complex. Cu(II) can promote the exchange adsorption of tryptophan on
      alpha-FeOOH surface. The diffuse reflectance IR spectra can give us some evidence
      for the structure of the ternary surface complex, and these results are in
      accordance with the results of the E (%)-pH curves.

PMID- 9241137
TI  - Pulsed Field Gradient NMR Self-Diffusion Study in Distinct Phases of the Ternary
      System Water/n -Heptane/Igepal CA-520
AB  - We report on self-diffusion measurements of all the components in distinct phases
      of the ternary system water/n -heptane/Igepal CA-520 with pulsed field gradient
      NMR. The phases are also investigated with electron microscopy. The observed self
      diffusion coefficients are discussed in comparison with the structural data
      obtained from the micrographs. They intimately reflect the effect of the phase
      state and phase boundaries on the molecular transport in this system.

PMID- 9241138
TI  - Blend of Electroactive Complexes of Polyaniline and Surfactant with Alkylated
      Polyacrylate
AB  - The cocrystallization of alkylated polyimides and polyesters, as shown by
      Ballauff et al., offers an opportunity to mix alkylated electrically conducting
      blends with the alkylated insulating materials. In this investigation we have
      used a flexible alkylated polymer to blend with a stiff alkylated conducting
      polymer. Comb-shaped poly(octadecyl acrylate) (PODA) was blended with polyaniline
      emeraldine base (PANI)/dodecyl benzenesulfonic acid (DBSA) complex to investigate
      the effect of long alkyl chain of flexible polymer on the electroactive rigid rod
      like PANI(DBSA)4 (weight ratio) complex. Binary blend DBSA/PODA was also used as
      a model to investigate the intermolecular interaction between unprotonated excess
      amounts of DBSA and PODA in the ternary blend. Cross-polarized optical microscope
      (OM) and wide-angle X-ray diffraction (WAXD) were applied to observe the highly
      ordered mesophase structure of these blends. This newly formed mesomorphic
      structure of DBSA/PODA binary blend due to the hydrogen bonding was observed when
      the PODA content was below 40 wt% in binary blend and these blend samples show a
      homogeneous one phase above 68&deg;C by OM. With addition of 10 wt% of PODA in
      ternary blend, the homogeneous smectic liquid crystalline structure was clearly
      confirmed by OM and WAXD. The intermolecular interactions that occurred in the
      blend systems was explained for each different characteristic peak with FT-IR
      spectra.

PMID- 9241139
TI  - Kinetics of Dissolution of beta-Tricalcium Phosphate
AB  - The rate of dissolution of beta-tricalcium phosphate (beta-Ca3 (PO4 )2 ; beta
      TCP) has been measured in the solution system Ca(OH)2 -H3 PO4 -NaOH-HNO3 -H2 O.
      The effects of different parameters such as pH, temperature, time, and saturation
      have been investigated. At zero saturation, the logarithm of the dissolution rate
      is a linear function of the pH (log(j 0 ) = 2.02 - 0.82 pH; r 2 = 0.993; in
      mmol/m2 s), indicating diffusion-limited dissolution. A simple calculation of the
      theoretical rate of a diffusion-controlled process showed that our data are
      consistent with theory. Moreover, the activation energy for this process is low
      (E act = 3.9 kcal/mol) also suggesting that the beta-TCP dissolution is
      controlled by diffusion processes. At increased saturation, the initial beta-TCP
      dissolution rate decreases much faster than that predicted assuming a diffusion
      controlled model. However, this latter model gives a good prediction of the
      results if it is assumed that beta-TCP dissolution is controlled by the
      dissolution of an interfacial layer of hydroxyapatite (Ca5 (PO4 )3 OH; HAp):
      log(j ) = -1.47 + 1.34 log(1 - S HAp ); r 2 = 0.959. The beta-TCP dissolution
      rate decreases very sharply with time. This effect increases at higher pH or
      saturation. Several explanations are proposed and discussed, even though none is
      conclusive.

PMID- 9241140
TI  - Microcalorimetric Studies of the Interactions of Lysozyme with Immobilized
      Cu(II): Effects of pH Value and Salt Concentration
AB  - In this investigation, employing a highly sensitive microcalorimeter, we measure
      the influence of pH value and salt concentration on the heat of interaction
      between lysozyme and CS-IDA-Cu(II) gel. The direct enthalpy measurement of the
      interaction provides thermodynamic information regarding the binding behavior of
      lysozyme toward the immobilized metal ion. The binding enthalpy altered by
      adsorbed lysozyme at various pH values and salt concentrations are measured. The
      findings, along with the reported binding isotherm, are discussed herein.

PMID- 9241141
TI  - An Algorithm for the Calculation of the Electrical Potential Distribution in a
      Charged Capillary with General Electrolytes
AB  - Knowledge of the electrical potential distribution is an essential basis for
      analyzing the flow behavior of electrolytes in a charged capillary, such as
      electroviscous effects. The cylindrical Poisson-Boltzmann equation (PBE) governs
      the distribution in the capillary. The PBE is a differential equation that is
      difficult to solve analytically, especially when the capillary is filled with
      general electrolytes. In this paper we propose a numerical algorithm to obtain
      the electrical potential distribution in a charged capillary filled with
      arbitrary electrolytes. First, we introduce a Poisson-Boltzmann integral equation
      (PBIE) governing the potential distribution and derived from the physical
      principles for electrostatic fields and thermodynamic systems. Then we solve the
      PBIE numerically by iteration. In numerical calculation only the discrete
      potential is used, and the potential differentials of the first and higher orders
      are not required. This algorithm essentially removes the difficulty caused by
      very steep variation of the potential near the wall of the capillary and is
      easily extended to cover the more general case of arbitrary electrolytes. The
      results of the examples given in the paper show that the algorithm proposed here
      is correct, effective, accurate (the relative errors are less than 0.01% when
      normalized surface potential xi </= 8), and easily implemented on a personal
      computer.

PMID- 9241142
TI  - Stability Factors of Foam Film in Contrast to Fluctuation Induced by Humidity
      Reduction
AB  - We have examined the relationship between dynamic surface properties of aqueous
      SDS solutions and foam film stability by observing the dynamic surface tension
      (gammat ), elongation of the lamellae (L lamellae ), and the thickness of the
      lamellae measured by FT-IR. Three foam film models were used by controlling such
      factors as the Marangoni effect by changing the SDS concentration, the disjoining
      pressure with the addition of electrolytes, and the surface viscosity with the
      addition of glycerin. In order to obtain information about the most effective
      factor in foam film stability, the lifetime of these films was measured under the
      circumstances of low relative humidity, at which vigorous fluctuation occured in
      the foam film. Foam film stability was found to be remarkably enhanced by the
      Marangoni effect and surface shear viscosity in a thin aqueous film at a relative
      humidity between 60 and 75%. Under these conditions, mild fluctuation would occur
      in the films. On the other hand, foam film stability was found to be maintained
      by the disjoining pressure in a thin aqueous film at the humidity below 60%.
      Under these conditions, vigorous fluctuation would occur in the foam film. It is
      concluded that foam film stability of an ionic surfactant solution mainly depends
      on the disjoining pressure which generates a repulsion force between the two
      surfaces in contrast to the vigorous fluctuation induced by humidity reduction.

PMID- 9241143
TI  - Effect of Ethanol on the Solubilization of Hydrocarbon Emulsion Droplets in
      Nonionic Surfactant Micelles
AB  - Light scattering was used to study the effects of ethanol on the mass transport
      of hydrocarbon molecules from emulsion droplets to nonionic surfactant micelles.
      n -Hexadecane oil-in-water emulsions (10 wt%) with a mean droplet diameter of
      0.97 &mgr;m stabilized by 2 wt% polyoxyethylene sorbitan monolaurate, were
      prepared. These emulsions were diluted to 0.04 wt% n -hexadecane using a series
      of aqueous solutions containing different concentrations of ethanol (0 to 20 wt%)
      and polyoxyethylene sorbitan monolaurate (0 or 2 wt%). The time dependence of the
      droplet concentration and size distribution were monitored at 30&deg;C using
      light scattering. The molecular flux of the solubilization process increased with
      increasing ethanol concentration, but the maximum amount of oil solubilized per
      unit amount of surfactant was independent of ethanol concentration. The data are
      interpreted in terms of the molecular processes that occur during solubilization.

PMID- 9241144
TI  - Preparation of Liposomes with a Controlled Assembly Procedure
AB  - A method of liposome preparation that involves two experimental steps is
      demonstrated. First, water in oil (W/O) emulsions are prepared by sonication.
      Then, due to centrifugal force, water droplets in the emulsion contact the
      monolayer at the oil/water interface and transform into liposomes after the
      monolayer has enwrapped the droplets. This procedure results in liposomes with
      diameters in the range 50-200 nm. Advantages of this procedure include relatively
      high (60%) encapsulation efficiency, direct preparation of liposomes in an
      aqueous medium different from the entrapped phase, and no leakage of the
      encapsulated chemicals during preparation. This relatively simple and rapid
      method may be useful in the encapsulation of drugs, enzymes, and other
      macromolecules as well as in the study of membrane properties.

PMID- 9241145
TI  - Rheology of Colloidal Particles in a Confined Channel under Shear Flow by
      Brownian Dynamic Simulations
AB  - A colloidal system of strongly charged particles, confined between two charged
      walls, is studied under static conditions and in the presence of shear flows.
      Brownian Dynamics simulations (BD) are used to determine the concentration
      profiles for several separations of charged walls. Results show good agreement
      with those obtained under static conditions using the Hypernetted Chain
      Approximation (HNC) and Monte Carlo simulations. Results obtained with BD and HNC
      for neutral walls show more similarities than those between BD and Monte Carlo
      simulations depending on the initial state of the colloidal particles. The
      presence of a shear flow field perturbs the equilibrium concentration profiles
      and the distribution function in the flow direction, generating a structureless
      system, as confirmed by the absence of peaks in the radial distribution function.
      The mobility of the particles in the transversal direction decreases rapidly and
      becomes practically frozen. The flow exhibits a non-Newtonian behavior with shear
      thinning viscosity. Due to the interparticle interactions and particle-wall
      interactions, the viscosity is lower as the wall separation decreases, giving
      rise to an apparent slip in the colloidal suspension. The slip velocity for
      repulsive walls is higher than that obtained with neutral walls and increases
      with the shear stress according to a power law, as observed in polymer solutions.
      The shear viscosity and the normal stress differences depend strongly on the
      combined effect of confinement, concentration of particles, magnitudes of inter
      particle interactions and wall-particle repulsion.

PMID- 9241146
TI  - Monte Carlo Simulations for Micellar Encapsulation
AB  - The solubilization of solutes in surfactant aggregates (micelles) is studied
      using lattice-based Monte Carlo simulations. Various properties such as the size
      and shape of the micelles, the critical micelle concentration, the locus of
      solubilization, and the partition coefficient of the solute are obtained, and the
      implications of the results for the thermodynamics of solubilization are
      examined. The presence of contaminants in the solution affects micellar
      properties by promoting micellization and stabilizing micelles. The ratio of head
      group size to tail group size for the surfactant is found to greatly affect both
      micellar properties and contaminant solubilization. The partitioning of the
      solute is found to be independent of surfactant concentration, but increases with
      solute concentration. The results show that contaminant partitioning is
      controlled primarily by enthalpic contributions.

PMID- 9241147
TI  - On the Spreading of an Insoluble Surfactant over a Thin Viscous Liquid Layer
AB  - Reported here are results of a theoretical and experimental study of the
      spreading of an insoluble surfactant over a thin liquid layer. Initial
      concentrations of surfactant above and below CMC have been considered. If the
      concentration is above CMC two distinct stages of spreading are found. (i) The
      first stage is the faster, and it is connected with micelle dissolution; (ii) the
      second stage is the slower, when the surfactant concentration falls below CMC. In
      the second stage, the formation of a dry spot in the center of the film is
      observed. A similarity solution of the corresponding equations for spreading
      gives good agreement with experimental observations.

PMID- 9241148
TI  - Thermal Behavior of a Nonfreezing Water Interlayer
AB  - The temperature dependence of the thickness of a nonfreezing water interlayer
      confined between an ice core and a smooth surface of quartz capillary is studied
      here theoretically. By using the principle of conservation of energy a first
      order differential equation is found. The equation relates the temperature and
      the film thickness via the film pressure (disjoining pressure). Molecular and
      structural components of this pressure are examined. Nonequilibrium and
      equilibrium solutions are compared with the respective experimental data. It is
      shown that disjoining pressure forces cause the lowering of the temperature in
      systems having confined phases.

PMID- 9241149
TI  - A Film Tension Theory of Phagocytosis
AB  - A film tension criterion is derived on the basis of which it is possible to
      evaluate the probability of a particle or vesicle being phagocytosed by
      phagocytic cells. Variations of this criterion are arrived at by mechanical and
      thermodynamical analyses. Specific receptor-ligand binding interactions are
      included in the analysis, as are electrostatic, steric repulsive, and van der
      Waals attractive interactions between the surface of the phagocytosed particle
      and the pseudopods of the host cell membrane. Cytoskeletal forces proximate to
      the membrane are also implicitly included in the approach. The film tension
      criterion is shown to reduce to the classical wettability criterion in the limit
      of purely passive phagocytosis, wherein there are no electrostatic, steric
      repulsive, or receptor-ligand binding interactions between the cell and the
      phagocytosed particle. Several formulas characterizing various aspects of
      phagocytosis are derived. Opsonized particles are demonstrated to be more readily
      phagocytosed than nonopsonized particles, owing both to the energy of specific
      binding between opsonins and cell receptors and to the lowering of membrane
      tension that occurs in the vicinity of spreading pseudopods as a result of
      spontaneous actin polymerization. It is shown that certain particles or vesicles
      (those that are most easily phagocytosed) tend to be ingested more readily with
      increasing particle size, while others (those less easily phagocytosed) tend to
      be ingested more readily with decreasing size. In the limit of purely passive
      phagocytosis, formulas are developed for predicting the relative volumetric and
      particle-number uptake by cells as a function of organic/water partition
      coefficients. Partition coefficients of polystyrene particles and polymerized
      liposomes were measured and used to make theoretical predictions of particle
      uptake by macrophages. These predictions are compared with phagocytic uptake data
      for hydrophilic and hydrophobic nano- and microparticles. The comparisons show
      agreement between predicted trends of volumetric and particle-number uptake as a
      function of particle size, with uptake of hydrophilic nanoparticles diminishing
      with increasing size and uptake of hydrophobic nanoparticles increasing with
      increasing size (at least for submicrometer particles that are relatively
      insensitive to gravitational forces). Additional comparisons between published
      experimental data and theoretical predictions are also made. The potential use of
      the theory in characterizing the tendency of drug-loaded polymeric particles to
      be engulfed by macrophages is emphasized.

PMID- 9241150
TI  - Nucleation Radius and Growth of a Liquid Meniscus
AB  - We consider a horizontal solid plate P placed above the free surface of a liquid
      L separated by a layer of air of thickness e ( approximately 0.1 mm). With
      suitable P /L pairs this layer of air is metastable for thicknesses e below a
      certain limit e c ( approximately 1 mm). We have found a way of setting up
      bridges connecting the liquid surface with the plate in a controlled way
      (axisymmetric meniscus of horizontal radius R ). The meniscus grows if R is above
      a certain threshold R c (e ). If R < R c the meniscus shrinks to zero. Our method
      allows precise measurements of R c (e ): We were able to do this using silicone
      oils and two types of plates P (with different contact angles). Our results are
      in good agreement with classical calculations by G. I. Taylor and E. Michael (J.
      Fluid Mech. 58, 625 (1973)). Furthermore, When R > R c (e ), we find that R grows
      linearly with time t and that dR dt ~ e -0.7 1 - e e c 2 .

PMID- 9241151
TI  - A Dynamic Model for the Attachment of a Brownian Particle Mediated by Discrete
      Macromolecular Bonds
AB  - A model is presented for the attachment of a Brownian particle to a surface
      mediated by both the conservative colloidal forces and the formation of
      macromolecular bonds. By considering Brownian motion and bond formation as
      coupled stochastic processes, the model derives a governing equation for the time
      dependent probability density of having a given number of bonds and separation
      distance from the surface. The model predicts the deposition rate of particles to
      a surface as a function of the physicochemical parameters of the binding
      molecules, including the density, interaction length, stiffness, and formation
      and dissociation kinetic rate constants. Furthermore, two limiting
      simplifications of the full model are explored which correspond to particle
      attachment rate limited by the rate of Brownian motion or by the rate of bond
      formation.

PMID- 9241152
TI  - Surface Activity of ABA-Type Nonionic Oligosaccharide Surfactants
AB  - We report on the surface activity of two novel ABA-type nonionic oligosaccharide
      surfactants: N,N '-dodecamethylene-bismaltonamide and N,N '-dodecamethylene
      bis(dextran aldonamide) (DEX-C12-DEX). Surface active properties, determined from
      surface tension measurements, were compared with results for AB-type counterparts
      containing the same hydrophobic segment, N -dodecylmaltonamide and N -dodecyl
      dextran aldonamide (DEX-C12). Surface tension measurements, including analysis of
      binary surfactant mixtures of DEX-C12 and DEX-C12-DEX show that the DEX-C12-DEX
      does not form micelles, but induces micelle formation of DEX-C12 at a critical
      total surfactant concentration and diblock mole fraction. We show the effects of
      oligosaccharide chain length and molecular geometry on surface activity and
      packing density and, with the aid of molecular models, discuss our results from
      the viewpoint of surfactant conformation.

PMID- 9241153
TI  - Characterization of Colloidal Silica and Its Adsorption Phenomenon with Silicon
      Base Surfactants with Relation to Film Strength
AB  - The strength of coated film containing silica can be attributed to the packing
      density of the silica particles and the extent of siloxane bond formation between
      them. The adsorption of a silicon-base surfactant on silica surfaces hinders such
      bond formation. Such adsorption occurs through hydrogen bonding between the free
      silanol on the silica surface and the oxygen of the PEO of a surfactant chain.
      Variation in surface properties of silica affects the formation of these hydrogen
      bonds. Colloidal silica particles show a large variation in surface
      characteristics, such as the aluminum content on the surface of the particles.
      These properties determine the surface charge of the silica particles, which is
      apparent from the variation in zeta potential and the amount of acid consumption
      prior to an inflection point being reached in titration curves. The concentration
      of acid required to reach the inflection point is higher for silica with higher
      Al(OH)4 - content. Higher levels of Al(OH)4 - cause less adsorption of the
      surfactant by preventing hydrogen bonding of silanol to PEO of the surfactant.
      Higher levels of surfactant adsorbed on silica lower the strength of the film due
      to the reduction of the extent of the siloxane bond formed between two silicon
      atoms.

PMID- 9241155
TI  - A Theoretical Model of Flotation Deinking Efficiency
AB  - The associated probabilities of each microprocess occurring in flotation deinking
      are employed in the development of a kinetic or population balance-type model of
      the overall flotation process. The overall model contains two kinetic constants:
      The first, k 1 , governs the overall probability of a free ink particle
      successfully being intercepted by and adhering to an air bubble; the second, k 2
      , is a measure of the probability that a particle/bubble aggregate pair will
      become unstable and split to yield a "new" free ink particle. The solution to the
      kinetic model is presented in terms of k 1 and k 2 , which are themselves
      functions of system parameters such as bubble and particle physical properties
      (e.g., diameter, density) and fluid properties (e.g., viscosity, surface
      tension). From this solution, a definition of theoretical flotation efficiency is
      presented, as well as definitions of other system performance parameters, and
      selected predictions are displayed.

PMID- 9241154
TI  - Adsorption Kinetics, Conformation, and Mobility of the Growth Hormone and
      Lysozyme on Solid Surfaces, Studied with TIRF
AB  - Interactions of recombinant human growth hormone and lysozyme with solid surfaces
      are studied using total internal reflection fluorescence (TIRF) and monitoring
      the protein's intrinsic tryptophan fluorescence. The intensity, spectra,
      quenching, and polarization of the fluorescence emitted by the adsorbed proteins
      are monitored and related to adsorption kinetics, protein conformation, and
      fluorophore rotational mobility. To study the influence of electrostatic and
      hydrophobic interactions on the adsorption process, three sorbent surfaces are
      used which differ in charge and hydrophobicity. The chemical surface groups are
      silanol, methyl, and quaternary amine. Results indicate that adsorption of hGH is
      dominated by hydrophobic interactions. Lysozyme adsoption is strongly affected by
      the ionic strength. This effect is probably caused by an ionic strength dependent
      conformational state in solution which, in turn, influences the affinity for
      adsorption. Both proteins are more strongly bound to hydrophobic surfaces and
      this strong interaction is accompanied by a less compact conformation.
      Furthermore, it was seen that regardless of the characteristics of the sorbent
      surface, the rotational mobility of both proteins' tryptophans is largely reduced
      upon adsorption.

PMID- 9241156
TI  - Adsorption of Lead Ions onto N -Isopropylacrylamide and Acrylic Acid Copolymer
      Microgels
AB  - The interaction of hydrolyzable lead ions with thermosensitive microgel
      dispersions of N -isopropylacrylamide modified with a range of acrylic acid
      comonomer concentrations has been investigated. The hydrodynamic diameter of the
      microgel particles was observed, by dynamic light scattering, to reversibly alter
      due to changes in either temperature or pH, or due to the presence of lead ions.
      The hydrodynamic diameter of all the microgel particles decreases with increasing
      temperature. However, upon increasing the pH, the anionic microgel particles
      increase in diameter at a fixed temperature, while in the presence of Pb(II) at
      pH 5, the hydrodynamic diameter of the anionic microgel particles decreases. The
      size of the homopolymer microgel does not vary with pH, nor in the presence of
      Pb(II). The adsorption isotherms of hydrolysable Pb(II) with the microgel
      particles were established as a function of pH. Lead ion adsorption was observed
      to not significantly alter with temperature and was demonstrated to be completely
      reversible to pH adjustment.

PMID- 9241157
TI  - A New Method for the Removal of Toxic Metal Ions from Acid-Sensitive Biomaterial
AB  - A new method (competitive adsorption method) for the removal of toxic heavy
      metals from acid-sensitive biomaterials was proposed and it was applied to the
      removal of cadmium from the mid-gut gland (MG) of scallop, Patinopecten
      yessoensis. Insolubilized humic acid, which has been developed in our laboratory,
      was used as a competitive adsorbent. A metal-complexation model was used to
      determine the adsorption characteristics of cadmium onto MG. Furthermore, the
      model was applied to the competitive adsorption system. The results showed that
      the competitive adsorption method enabled the simultaneous removal of toxic
      cadmium from both liquid and MG phase under mild acidic condition (pH 5).

PMID- 9241158
TI  - The Effect of the Ionic Strength on the Adsorption Isotherms of Nickel on Silica
AB  - Isotherms of adsorption of Ni(II) on silica from 0.01 M NaClO4 are almost linear
      with a log-log slope of 0.95, and the percentage of uptake at a given pH is
      insensitive to the initial Ni concentration. At higher ionic strengths (>/=0.1
      mol dm-3 ) two kinds of behavior are observed. For low Ni concentrations the
      adsorption is approximately equal to that observed at lower ionic strengths. For
      higher Ni concentrations (but still much lower than the concentration of surface
      sites) the Ni adsorption from 0.1 and 0.3 mol dm-3 NaClO4 is lower than the
      adsorption from 0.01 M NaClO4 by a factor of 2 (pH 9) to 3 (pH 8). When water is
      replaced by a mixed solvent (e.g., 2% aqueous DMSO, THF, methanol, glycerol) the
      Ni adsorption isotherms obtained in the presence of 0.1 mol dm-3 NaClO4 are
      linear with a log-log slope of 0.95. These adsorption isotherms are rather
      insensitive to the nature and concentration of the organic cosolvent. It is
      impossible to explain the Ni adsorption curves over the entire studied range of
      initial concentrations and ionic strengths in terms of surface complexation
      model, unless the Boltzmann factor is properly corrected.

PMID- 9241159
TI  - Electrokinetic Behavior of Fluoride Salts as Explained from Water Structure
      Considerations
AB  - Unlike the other silver halides, silver fluoride is positively charged in its
      saturated solution as determined by nonequilibrium electrophoresis measurements.
      In the absence of surface hydrolysis reactions, other fluoride salts (LiF, CaF2 ,
      and MgF2 ) also are positively charged in their saturated solutions. Furthermore,
      the electrokinetic behavior of these fluoride salts is rather insensitive to the
      fluoride ion activity in neutral or acidic solutions, and reversal of the sign of
      the surface charge by fluoride addition is not possible. Based on FTIR
      transmission spectra to describe the water structure of ionic solutions, in situ
      FTIR/internal reflection spectroscopy (FTIR/IRS) has been used to
      spectroscopically characterize interfacial water at fluoride salt surfaces. The
      experimental spectra were examined by consideration of the O-H stretching region
      (3000-3800 cm-1 ) associated with the vibrational spectra of interfacial water.
      These results reveal a unique hydration state for fluorides and explain the
      anomalous electrokinetic behavior of fluoride salts such as LiF, CaF2 , and MgF2
      , which show an unexpected insensitivity to the fluoride ion concentration in
      solution. It appears that this insensitivity is due to the formation of strong
      hydrogen bonding of the fluoride ions with water molecules. This hydration state
      prevents the accommodation of excess fluoride ions at surface lattice sites and
      accounts for the observed electrokinetic behavior.

PMID- 9241160
TI  - Binding Kinetics for Biosensor Applications Utilizing Fractals: A Categorization
AB  - Analyte-receptor binding reactions occurring on biosensor surfaces are
      categorized using a fractal analysis. Both a single- and a dual-fractal analysis
      are utilized to describe the analyte-receptor binding kinetics. The three
      categories presented to describe the binding kinetics include (a) case I-only a
      single-fractal analysis is utilized, (b) case II-a single- and a dual-fractal
      analysis are utilized (implying a change in the binding mechanism), and (c) case
      III-only a dual-fractal analysis is utilized. This is an initial attempt to
      categorize surface binding kinetics. The categorization provides one possible
      means of classifying analyte-receptor reactions occurring on biosensor surfaces.
      The analysis should help to improve biosensor performance parameters. The
      analysis is, in general, extendable to analyte-receptor reactions occurring on
      other surfaces.

PMID- 9241161
TI  - Considerations about the Adsorption of Organic Molecules from the Gas Phase to
      Surfaces: Implications for Inverse Gas Chromatography and the Prediction of
      Adsorption Coefficients
AB  - Whether surfaces are characterized from experimental gas-phase adsorption
      coefficients of probe molecules with known properties (as is done in inverse gas
      chromatography (IGC)) or whether adsorption coefficients are to be predicted from
      known properties of the adsorbate and the adsorbent (as is desirable in
      environmental chemistry) in both cases a correct quantitative description of the
      van der Waals and acid-base interactions of organic molecules at surfaces is
      necessary. The model used to date in IGC for the van der Waals interactions
      tacitly assumes that the interactions of a dilute gas with a surface can be
      treated like the interactions between two condensed phases. This only works if
      the contact area of the adsorbed molecule is treated as an adjusted parameter
      which makes up for the occurring discrepancies. In this paper an improved
      equation for the van der Waals interactions will be suggested which works without
      adjusted parameters. For describing acid-base interactions of dilute gases at
      surfaces Gutmann's donor and acceptor numbers have found wide use in the IGC
      literature. However, these parameters are related to the heats of the acid-base
      interactions rather than the free energies. Thus this approach has the
      disadvantage of putting the acid-base characterization of surfaces in IGC on a
      different basis than the van der Waals characterization, and it also does not
      allow the prediction of gas-phase adsorption coefficients. Here, a different
      approach will be discussed that was originally introduced by van Oss and
      coworkers for the acid-base interactions between condensed phases (1). This
      approach uses acceptor and donor parameters that are free energy related.
      Validation with experimental data from the literature shows a good performance of
      the equations introduced in this paper for IGC purposes as well as for the
      prediction of gas-phase adsorption coefficients.

PMID- 9241162
TI  - A Nonlinear Three-Dimensional Rupture Theory of Thin Liquid Films
AB  - A process of nonlinear three-dimensional rupture of thin liquid films is
      numerically analyzed for the first time. With the rupture time being successfully
      calculated, it has been possible to develop a more complete rupture theory for
      thin liquid films. In contrast to the linear analysis indicating the shortest
      rupture time of thin liquid films to be the same for both two- and three
      dimensional rupture, the nonlinear analysis reveals that the latter proceeds
      faster than the former. In particular, among all three-dimensional disturbance
      modes, the symmetric one makes the thin liquid films rupture fastest. It is
      concluded that the rupture process develops at a point rather than along a line
      on thin liquid films.

PMID- 9241163
TI  - A Model for Detachment of a Partially Wetting Drop from a Solid Surface by Shear
      Flow
AB  - Liquid drop detachment from a solid surface by simple shear flow is modeled based
      on the experimental observations available in the literature. A liquid drop
      adhered to a solid surface deforms in the presence of a simple shear flow to form
      an advancing and a receding dynamic contact angle. The drop slides on the solid
      surface when the drag due to the shearing fluid overcomes the retentive force due
      to the contact angle hysteresis. A drop having an equilibrium contact angle,
      thetae , approaching 180&deg; detaches from the solid surface at the onset of its
      sliding motion. However, a drop with thetae much lower than 180&deg; slides on
      the solid surface and will not detach. With further increase in the shear rate,
      the sliding drop detaches from the solid surface when the lift force equals the
      adhesive, gravitational, and buoyancy forces of the drop. Based on this premise,
      an approximate mathematical model for the detachment of a partially wetting drop
      is constructed. The experimental results available in the literature for Pristane
      and Squalane drop detachment are compared for slide and lift as the mode of
      detachment. The critical shear rate for the detachment of Pristane drops, having
      thetae of 175&deg;, is predicted well by the model where sliding as the mode of
      detachment is assumed, whereas the experimental data for Squalane drops, having
      thetae of 126&deg;, is well predicted by the model where lift is considered the
      mode of detachment.

PMID- 9241164
TI  - Evaluation of the Low-Energy Value for the Adsorption Energy Distribution
      Function
AB  - This note presents an analytical method for calculating the minimal energy
      required to evaluate overall adsorption using Dubinin-Radushkevich theory. The
      method produces a result that is at least two orders of magnitude more accurate
      than that possible with numerical techniques.

PMID- 9241165
TI  - Cholesterol Binding to Simple Micelles in Aqueous Bile-Salt-Cholesterol Solutions
AB  - The true thermodynamic activity (A T ) of cholesterol (Ch) in aqueous solutions
      containing taurocholate (TC)-Ch was determined by employing a direct assay of a 1
      x 2-cm silicone polymer film with 0.025 cm thickness. Using the A T data,
      information on the nature of micellar species present in the TC-Ch system, and
      employing a binding-site model previously developed for tauroursodeoxycholate
      (TUDC)-Ch and taurochenodeoxycholate (TCDC)-Ch systems, it appeared that the Ch
      binding affinity for simple bile-salt micelles corresponds precisely with the
      order of hydrophobicity, TUDC < TC < TCDC. Further, although simple TC micelles
      and simple TCDC micelles have similar binding capacities, the first Ch binding to
      a simple TC micelle may not significantly facilitate the second Ch binding, as
      occurs in simple TCDC micelles. For TUDC-Ch, TC-Ch, and TCDC-Ch systems, the
      concentration of bound simple micelles increased with increasing A T values,
      whereas the unbound simple micelle concentration decreased proportionally. These
      results provide insights into the possible influence of bile-salt species on Ch
      binding to simple micelles in bile-salt-Ch solutions.

PMID- 9241166
TI  - Kinetics of the Formation of Goethite in the Presence of Sulfates and Chlorides
      of Monovalent Cations
AB  - The synthesis of goethite by oxidation of Fe2+ in presence of metallic iron was
      undertaken in an aqueous medium containing indifferent salts such as Na2 SO4 ,
      (NH4 )2 SO4 , NaCl, and NH4 Cl. Temperature and bubbling air rate were
      maintained, respectively, at 70&deg;C and 1 L/min. The influence of anions and
      cations on the kinetics of each step of the process has been followed distinctly,
      the iron dissolution rate has been determined by the variation of the medium
      acidity, and the precipitation of goethite has been determined by gravimetric
      measurements. With respect to Cl- , the SO4 2- anion decreases the rate of the
      two reactions. NH4 + acts as an inhibitor when it is present at low
      concentrations and as an accelerator for higher concentrations; the limit
      corresponding to the change of NH4 + behavior depends on the nature of the
      counter ion. The reaction product is composed of pure goethite in the presence of
      sulfate salts, whereas a mixture of goethite and lepidocrocite, respectively, 60
      70 and 40-30%, was observed in the presence of chloride salts.

PMID- 9241167
TI  - Effect of Lipid Phase State and Foam Film Type on the Properties of DMPG
      Stabilized Foams
AB  - The drainage and stability of DMPG (l -alpha-phosphatidyl-dl -glycerol
      dimyristoyl) foams were studied by a microconductivity method under conditions
      where three different foam film types could be formed-thin foam films (TFF),
      common black foam films (CBF), and Newton black foam films (NBF). Foaming
      properties were investigated at 20 and 28&deg;C where DMPG is in the gel and
      liquid-crystalline states. Higher conductivity signals were observed at the
      higher temperature where DMPG was in the liquid-crystalline state, which is
      indicative of wetter or more stable foams under these conditions. This effect was
      observed independent of foam film type. However, for a given phase state, the
      type of foam films formed significantly influenced the stability and rate of
      drainage of the foam. Indeed, the water content of the foams, obtained under
      conditions for formation of different foam films, is ranked in the order TFF >
      CBF > NBF. When the temperature was increased to 28&deg;C (i.e., in the liquid
      crystalline state), CBF and NBF showed a slight decrease in film thickness and an
      increase in film lifetime and surface molecular diffusion coefficient in the
      adsorbed layer. It is likely that the fluidity of the interfacial layer is an
      important factor contributing to DMPG foam stabilization.

PMID- 9241168
TI  - Thermodynamic and Dynamic Properties of Micellar Aggregates of Nonionic
      Surfactants with Short Hydrophobic Tails
AB  - The densities and viscosities of binary aqueous mixtures of
      poly(ethylenoxide)hexanols [C6 H13 (OCH2 CH2 )m OH, C6 Em ] (m = 3, 4, and 5)
      have been studied in the micellar composition range. For the same surfactants the
      self-diffusion coefficients in mixtures with heavy water have been determined by
      the spin-echo pulsed field gradient method. The volumetric data are interpreted
      by means of the phase separation model, and values of the CMC, volume change, and
      standard free energy change of micellization are obtained. From the viscosity
      data the hydration numbers of the surfactant hydrophilic head in the micellar
      state are computed; they are in agreement with those obtained from HDO self
      diffusion data. The surfactant self-diffusion data are used to calculate the
      apparent micelle radius and the aggregation number. The micellization parameters
      obtained for the different surfactants are compared and discussed.

PMID- 9241169
TI  - Random-Walk Aggregation Phenomena in Solid Bimodal Liquid Dispersions: Transition
      to Nondeterminism from Si3 N4 to Si3 N4 + Al2 O3 Aqueous Systems
AB  - This paper, which is based on another recent work, (Mezzasalma, S. A., Phys. Rev.
      E 55 (4), (1997)) deals with experiments and theory concerning an aqueous
      dispersed system formed from silicon nitride (Si3 N4 ), alumina (Al2 O3 ), and
      mixed silicon nitride + alumina (Si3 N4 + Al2 O3 ) solid agglomerates. From
      titration data applied to a thermodynamic equilibrium condition, the minimum
      number of each agglomerate species and their maximal average dimensions have been
      derived as functions of the aqueous solution pH. These parameters are of the
      order of, respectively, (1-2) &mgr;m for Si3 N4 and Al2 O3 agglomerates and (20
      50) &mgr;m for the mixed agglomerates. The numbers of solid particles of all
      species are poorly correlated with changes in pH of the liquid phase. This
      behavior has been interpreted as intrinsically related to the complexity of the
      system which, due to the many interactions among the different species, probably
      becomes nondeterministic. In order to describe such behavior a probabilistic
      approach has been developed. The probability of finding a given solid agglomerate
      number within a scatter band varies with the suspension pH. Furthermore, the
      scatter band amplitude becomes negligible near the isoelectric point.
      Accordingly, only the numbers of aggregates derived in the neighborhood of the
      isoelectric point are predictable.

PMID- 9241170
TI  - Effect of Mixing Entropy on the Static Yield Stress of a Liquid Dispersion of
      Solid Particles: Comparison between Si3 N4 and Ca3 (PO4 )2 Aqueous Suspensions
AB  - Experimental measurements of the static yield stresses tau of silicon nitride
      (SN, Si3 N4 ) and alpha-tricalcium phosphate (TCP, alpha-Ca3 (PO4 )2 ) aqueous
      dispersions have been performed for different pH values of the liquid medium and,
      as a result, the two tau vs pH behaviors are quite different. In agreement with
      the DLVO theory, the static yield stress value for silicon nitride is maximal at
      the isoelectric point of the slurry (pHiep (SN) = 8.0 &plusmn; 0.1) and, for
      higher and/or lower suspension pH values, it decreases progressively. On the
      other hand, in tricalcium phosphate dispersed systems, the maximum value of tau
      is not observed at the isoelectric point (pHiep (TCP) = 6.7 &plusmn; 0.1) but two
      relative maximum values, taua and taub , are observed for two suspension pH
      values in the acid/basic environments, namely, for pH <> pHiep (TCP) . First,
      displacements of the pH from the isoelectric point in both environments are
      accompanied by an increase in tau; second, after the maximum tau values have been
      reached, the static yield stress decreases with the increase in the [H+ ]/[OH+ ]
      ions in the solution. It is shown that this phenomenon can be interpreted as an
      effect of the mixing entropy relative to the solid TCP aggregates, which is very
      sensitive to the suspension pH. Phenomenological and theoretical explanations are
      developed, respectively, by a heuristic recasting of the Hamaker expression for
      the London-van der Waals forces and by a relationship between the static yield
      stress and the number of solid aggregates; this relation is based on recently
      proposed methods for investigating the agglomeration/adsorption phenomena in a
      dispersed system.

PMID- 9241171
TI  - Study of the Gelation Process of Polyethylene Oxidea -Polypropylene Oxideb 
      Polyethylene Oxidea Copolymer (Poloxamer 407) Aqueous Solutions
AB  - The gelation process of polyethylene oxidea -polypropylene oxideb -polyethylene
      oxidea copolymer (poloxamer 407) aqueous solutions is studied by means of FTIR
      spectroscopy, rheology, and differential scanning calorimetry (DSC). The C-O-C
      stretching bands of infrared spectra were found to shift toward higher
      wavenumbers with sol-gel transition, indicating that hydrogen bonding is not the
      driving force for gelation. Linear viscoelastic data provide an alternative
      method for gel point determination of these thermoreversible gels. The results
      obtained with this method are found to coincide with those obtained using DSC.
      Gel point temperatures determined by these methods are close to 14 degrees C for
      25% (w/w) poloxamer 407 solutions and 10 degrees C for 30% (w/w) solutions. In
      gel state, the elastic modulus (G ') and dynamic viscosity (eta*) are found to be
      concentration and temperature independent for temperatures ranging from 20 to 35
      degrees C. In light of our results, we suggest a mechanism of gelation based on
      micelles packing and entanglements.

PMID- 9241172
TI  - Adsorption of Hydrophobized Glucose Oxidase at Solution/Air Interface
AB  - The modification of glucose oxidase by palmitic acid ester of N 
      hydroxysuccinimide leads to the formation of a new hydrophobized enzyme with five
      covalently bound C16 groups. Such a modification was shown not to alter
      noticeably the native structure of the enzyme. The modified glucose oxidase
      displays enhanced surface activity at the water/air interface in comparison with
      the native enzyme. The maximum reduction of surface tension at all concentrations
      studied was higher for the modified glucose oxidase than for the native one. The
      modified enzyme also displayed a much steeper rise of the surface potential with
      time and a much more rapid attainment of the saturation plateau than the
      unmodified enzyme.

PMID- 9241173
TI  - Adsorption of Tungstophosphoric or Tungstosilicic Acids from Ethanol-Water
      Solutions on Carbon
AB  - The equilibrium adsorption on activated carbon of tungstophosphoric or
      tungstosilicic acid, both from solutions in ethanol-water 50% v/v, was studied at
      20degreesC. It was found that the adsorption strength was higher for the former
      acid than it was for the latter. The solutions were characterized by UV-visible
      and 31 P nuclear magnetic resonance spectroscopies and the results indicated that
      the main species present are the undegraded anions of the acids. This behavior is
      opposite that observed in aqueous solutions in which, depending on the
      heteropolyacid considered, different transformations take place. The solids
      obtained, which were dried at 20degreesC and studied by X-ray diffraction,
      contain highly dispersed noncrystalline adsorbed species. By 31 P nuclear
      magnetic resonance and Fourier transform infrared spectroscopies on the solids,
      it was found that such species are the anions [PW12 O40 ]3- and [SiW12 O40 ]4-
      with undegraded structure for the tungstophosphoric and tungstosilicic acids,
      respectively. Besides, it was proved that the thermal behavior up to 365degreesC
      of the adsorbed species is similar to that of their corresponding bulk acids,
      i.e., neither tungstophosphoric nor tungstosilicic acid undergoes degradation.

PMID- 9241174
TI  - Light Scattering Experiments on Shear Induced Structures of Micellar Solutions
AB  - The formation of shear induced structures (SIS) of a mixed micellar solution of
      tetradecyldimethylaminoxide and sodium dodecylsulfate is studied by light
      scattering experiments under shear (rheo-optical method). In the shear rate- as
      well as in the time-dependent measurements we found an aggregation process taking
      part in the SIS formation. Below the critical shear rate for the occurrence of
      SIS, the shear rate dependent experiments show an increased scattering intensity,
      indicating micellar associates. Above the critical shear rate, we found
      structures oriented in the direction of flow. The time dependent measurements
      show that the SIS formation can be regarded as a process which can be divided
      into three stages: induction-aggregation-orientation. After the aggregation, we
      found a temporal process in which the orientation increases to reach complete
      orientation in the direction of flow.

PMID- 9241175
TI  - Correlation of the Dielectric Properties of Dispersed Particles with the
      Electrorheological Effect
AB  - The dc field rheological properties and frequency dependent dielectric properties
      of a set of electrorheological (ER) fluids composed of oxidized polyacrylonitrile
      or aluminosilicate materials dispersed in silicone oil were examined in this
      paper. Our experimental investigations show that there is a complicated
      relationship between the dielectric properties of dispersed particles and the ER
      effect. The dielectric loss of dispersed particles, which has not attracted much
      attention in previous work, was found to play a considerable role in ER response.
      The large dielectric loss tangent, experimentally around 0.10 at 1000 Hz, is
      found to be needed for a strong ER effect. A good ER solid material should first
      have large dielectric loss, and then the higher the dielectric constant, the
      stronger the ER effect. The large dielectric loss would facilitate the turning of
      dispersed particles, and the high dielectric constant would maintain the
      fibrillation structure stable and strong. Two processes, the particle turning
      process and the particle polarization process, are thought to be involved in ER
      activity. Our findings, in connection with the Wagner model, can better explain
      why the strongest ER effect occurs at particle conductivity of 10(-7) S/m; why
      the shear stress of some ER fluids decreases with frequency while with others the
      shear stress increases with frequency; and why trace water can enhance the ER
      effect considerably, which would help in understanding the mechanism of the ER
      effect. Too large a dielectric loss is thought to be unfavorable for the ER
      effect, and its suitable range is worth further study. The results also present a
      method of designing high performance ER fluids, which would significantly promote
      development of electrorheology and its application in industrial areas.

PMID- 9241176
TI  - Vibration Spectroscopy Study of Phenylphosphonate at the Water-Aluminum
      (Hydr)Oxide Interface
AB  - Two previously published surface complexation models of phenylphosphonate on aged
      gamma-Al2 O3 and boehmite (gamma-AlOOH), respectively, have been examined by
      means of FTIR and FT-Raman spectroscopy. The spectral features of adsorbed
      phenylphosphonate were studied as a function of pH and total phenylphosphonate
      concentration. No evidence for a phase transformation into a three-dimensional
      aluminum phenylphosphonate phase was found. This suggested that phenylphosphonate
      is sorbed as surface complexes under the conditions used in this study. Both the
      infrared and the Raman data showed that the surface-bound phenylphosphonate ions
      undergo protonation reactions as pH is varied. These results together with the
      fact that the ligand has only two donor atoms for complexation and protonation
      led to the conclusion that a monodentate coordination to the surface is most
      likely in both systems. Overall, the spectroscopic results were in good
      qualitative agreement with the thermodynamic surface complexation models.

PMID- 9241177
TI  - Adsorption of Pure Nonionic Alkylethoxylated Surfactants down to Low
      Concentrations at a Silica/Water Interface as Determined Using a HPLC Technique
AB  - The adsorption of pure nonionic alkylethoxylated surfactants of the C12 En series
      at silica/water interface has been determined using a very precise HPLC
      technique. The number of ethoxylated groups was varied from 2 to 9. The
      adsorption isotherms were constructed with special attention to the very low
      surface coverage domain. It is shown that at very low concentration, the
      adsorption amounts are higher as the number of ethoxylated groups increases but
      the reverse trend is found at higher surfactant concentration and above the
      critical micelle concentration. It is shown that this behavior is the consequence
      of the interplay of the primary and secondary adsorption mechanisms depending
      upon the length of the ethoxylated chain. The maximum adsorption quantities is
      not a linear function of the number of ethoxylated groups. This and other
      observations confirm the viewpoint that the behavior of nonionic surfactant
      aggregates adsorbed at a hydrophilic surface carries many similarities with the
      properties of this class of nonionic surfactant aggregates in bulk aqueous
      solutions.

PMID- 9241178
TI  - Fractal Dimensions of Coals and Cokes
AB  - Using adsorption data, we get formulas for the calculation of fractal dimensions:
      log[A CO2 (DP) /A N2 (BET) ] = -5.3984(2 - D 1 )/2 and log[A CO2 (BET) /A N2
      (BET) ] = -4.9569(2 - D 2 )/2. The fractal dimensions (D ) of 27 coals and 2
      cokes have been obtained. The D of coals decreased with the increase of fa and
      reached a maximum at H/C equal to 0.66 (or C daf about 86%). The fractal
      dimension is relative to ash and volatiles of coal: D = 2.2237 + 0.6249V daf +
      0.8863A d . The relationship between D of coal coke and its conversions (X )
      obeys the following equation: D = a exp(-bX ) + c .

PMID- 9241179
TI  - Electrostatic Interactions and Stability of Poly-l -lysine Covered Polystyrene
      Latex Particles Investigated by Dynamic Light Scattering
AB  - Adsorption isotherms of the pH dependent positively charged polyelectrolyte poly
      l -lysine (PLL) on negatively and positively charged polystyrene latices are
      determined. With photon correlation spectrometry (PCS) the influence of the
      fluctuating PLL domaines in solution on the diffusion coefficient is observed at
      low salt concentrations c NaBr < 10(-3) M with lambda = c PE /c NaBr < 0.1 (c PE
      = concentration of the polyelectrolyte units). Screening of the charged layer by
      increasing electrolyte concentration results in large adsorbed amounts and layer
      thicknesses. At low molar mass of PLL the suspensions become unstable and the
      state and kinetic of flocculation is followed by the decreasing diffusion
      coefficient. PLL of higher molar mass (M w >/= 100 000) stabilizes the particles
      sterically and the adsorbed layer thicknesses can be determined. The conclusions
      drawn from PCS features are confirmed directly by raster electron micrographs of
      the filtered particles.

PMID- 9241180
TI  - Electrostatic Interaction between Two Ion-Penetrable Charged Spheroids
AB  - The electrostatic interaction between two ion-penetrable, charged spheroidal
      particles is examined theoretically. These particles can assume different sizes
      and an arbitrary spatial orientation. The electrical potential distribution is
      derived analytically under the Debye-Huckle condition. The results for two
      interaction spheres, one spheroidal particle and a planar surface, and rigid
      particles covered by an ion-penetrable membrane can be recovered as the special
      cases of the present general problem. We show that, for a fixed center-to-center
      distance between two particles, regardless of their relative sizes, the
      interaction free energy is the greatest if their major axes lie on the same line
      (head-to-head), and the smallest if their major axes are perpendicular to each
      other but not on the same plane (perpendicular).

PMID- 9241181
TI  - Immobilization of Polymer-Stabilized Noble Metal Colloids and Their Catalytic
      Properties for Hydrogenation of Olefins
AB  - Polymer-stabilized noble metal colloids were efficiently immobilized on silica by
      the addition of organic acids under mild conditions. The function of organic
      acids in the immobilization was studied by infrared spectroscopy. Transmission
      electron micrographs indicate that the immobilized colloids have a controlled
      particle size and size distribution. They serve as catalysts in the hydrogenation
      of cyclohexene and cyclopentadiene, the results of which show that this new type
      of immobilized colloid has high selectivity and good stability.

PMID- 9241182
TI  - Size Modulation of Polymeric Nanoparticles under Controlled Dynamics of
      Microemulsion Droplets
AB  - Polyacrylamide nanoparticles of different size (<100 nm) were prepared in reverse
      micelles under various dynamic conditions of micellar systems. The nanoparticles
      were always larger than the aqueous core in which they were formed; however, the
      size of the nanoparticles could be controlled if the interdroplet interaction and
      coalescence rate in reverse micelles were regulated. Factors such as interfacial
      rigidity of the droplets, size of the aqueous core, temperature, and
      concentrations of acrylamide (monomer) and N ,N '-methylenebisacrylamide
      (crosslinking agent) have a profound effect on the size of nanoparticles. By
      adjustment of these parameters in reverse micelles, nanoparticles ranging from
      about 10 to more than 100 nm have been prepared.

PMID- 9241183
TI  - Measurement of Colloidal Stability in Solutions of Simple, Nonadsorbing
      Polyelectrolytes
AB  - The stability of a solution of charged polystyrene particles in the presence of
      nonadsorbing polyelectrolyte macromolecules is measured using optical light
      scattering. The particles were negatively charged polystyrene latex spheres (0.5
      1 &mgr;m diameter) while the macromolecules were simulated using negatively
      charged colloidal silica spheres (5-7 nm diameter). Because of the electrostatic
      repulsion between the particles, the solution is found to be stable against
      primary flocculation (irreversible flocculation into a primary energy minima).
      However, because of long-range attractive depletion forces, reversible secondary
      flocculation of the particles occurs into a local potential energy minimum. As
      observed with uncharged macromolecules, the polyelectrolyte first induces
      flocculation at a critical flocculation concentration (v *), but later
      restabilizes the system at a critical restabilization concentration (v **). These
      critical concentrations are found to decrease with decreasing macromolecule size
      and increasing particle size. The restabilized solutions are found to remain
      suspended for periods greater than 20 days. Comparison of the measured
      flocculation and restabilization results to predictions made using a recently
      developed force-balance model show qualitative agreement.

PMID- 9241184
TI  - Thermodynamics of Adsorption of n -Alkanes on Maleated Wood Fibers by Inverse Gas
      Chromatography
AB  - The adsorption of n -heptane, n -octane, n -nonane, and n -decane on untreated
      wood fiber and wood fiber treated with maleated polypropylene was studied by
      inverse gas chromatography (IGC) at infinite dilution or zero surface coverage.
      The specific retention volume increased with increasing probe chain length,
      decreased with increasing column temperature, and increased with increasing
      maleated polypropylene concentration. The enthalpy of adsorption increased with
      increasing chain length of the probe vapors. The enthalpy of adsorption remained
      constant after the treatment of wood fiber. The London dispersive component of
      the surface free energy decreased with the column temperature and showed no
      dependency with either the type of wood fiber or the maleated polypropylene
      concentration.

PMID- 9241185
TI  - Characterization of Silica-Containing Aluminum Hydroxide and Oxide Aerogels
AB  - Pure and silica-containing Al hydroxide aerogels were prepared by the
      supercritical drying method. The samples were later calcined, giving rise to
      alumina and Si-Al mixed oxides. The materials were characterized from the points
      of view of their bulk and surface structures. The Si-free material before
      calcination is well-crystallized boehmite that converts to gamma-alumina by
      calcination. The silica-containing hydroxides are composed of boehmite layers
      with silicates in the interlayer region. The resulting mixed oxides present
      silica essentially in the bulk. The surface structure of alumina seems poorly
      sensitive to silica addition. Surface silanol groups appear only for SiO2 more
      than 4%. No Bronsted acidity appears. Silica addition allows mixed oxides with
      higher surface areas to be obtained.

PMID- 9241186
TI  - Interaction of Silane Coupling Agents with CaCO3
AB  - A study of eight silane coupling agents showed very different effect of these
      compounds on the mechanical properties of PP/CaCO3 composites. The application of
      aminofunctional silane coupling agents resulted in the reactive coupling of the
      two inactive components leading to increased strength and decreased
      deformability. A detailed study of the interaction between CaCO3 and the various
      coupling agents was carried out in order to find an explanation for the strong
      coupling effect. The amount of coupling agent creating a monolayer coverage was
      determined by a dissolution method for each coupling agent. The obtained values
      changed between 0.3 and 1.0 wt% calculated for the CaCO3 . An attempt was made to
      determine the orientation of the adsorbed molecules to the filler surface. Most
      of the coupling agents are oriented perpendicularly to the surface with the
      exception of a methacryl functional silane compound. Possible interactions
      between hydrolyzed or condensed silane coupling agents and the filler were
      studied by Fourier transform infrared spectroscopy using transmitting (FTIR-TS)
      and diffuse reflectance (DRIFT) modes, as well as gel permeation chromatography
      (GPC). The results showed that bulky organofunctional groups form a caged,
      polycyclic, low-molecular-weight structure on the surface, while silanes with
      smaller groups tend to condense into open, ladder type, high-molecular-weight
      polysiloxane chains. Polymer/filler adhesion, however, depends primarily on the
      chemical character of the organofunctional group. Aminofunctional silane coupling
      agents adhere well to the filler surface and react also with the polymer. In the
      case of similar functionality the size of the organofunctional group determines
      the strength of the adhesion.

PMID- 9241187
TI  - Structure, Stability, and Activity of Adsorbed Enzymes
AB  - A proteolytic enzyme, alpha-chymotrypsin, and a lipolytic enzyme, cutinase, were
      adsorbed from aqueous solution onto a hydrophobic Teflon surface and a
      hydrophilic silica surface. We investigated the influence of adsorption on the
      structure, the structure thermal stability and the activity of these enzymes.
      Probing the protein structure by circular dichroism spectroscopy indicates that
      Teflon promotes the formation of helical structure in alpha-chymotrypsin, but the
      reverse effect is found with cutinase. The perturbed protein structures on Teflon
      are remarkably stable, showing no heat-induced structural transitions up to
      100&deg;C, as monitored by differential scanning calorimetry. Contact with the
      hydrophilic silica surface leads to a loss in the helix content of both proteins.
      Differential scanning calorimetry points to a heterogeneous population of
      adsorbed protein molecules with respect to their conformational states. The
      fraction of the native-like conformation in the adsorbed layer increases with
      increasing coverage of the silica surface by the proteins. The specific enzymatic
      activity in the adsorbed state qualitatively correlates with the fraction of
      proteins in the native-like conformation.

PMID- 9241188
TI  - Microemulsions with Didodecyldimethylammonium Bromide Studied by Neutron Contrast
      Variation
AB  - The structure of water-in-oil microemulsion droplets, stabilized by
      didodecyldimethylammonium bromide (DDAB), has been investigated by small-angle
      neutron scattering (SANS). Detailed information about the curved surfactant film
      has been obtained by selectively deuterating the water, DDAB, and cyclohexane
      components. For each surfactant h -DDAB and d -DDAB and concentration, three sets
      of complementary neutron contrast data were analyzed together in terms of a
      Schultz distribution of core-shell particles. The modeling was consistent with a
      simple liquid-like surfactant layer, of density 0.80 g cm-3 , with no evidence
      for any solvent penetration. This film thickness was found to be 11-12 A, about
      70% of an all-trans C12 chain length. At the water interface the area per head
      was 56-61 A2 , while for the alkyl chains at the outer surface it was 90-125 A2
      (15-30% lower than that for a truncated cone molecular configuration). The
      cyclohexane-water interfacial tensions gammao/w , measured by surface light
      scattering, were used along with the droplet polydispersities to find that the
      rigidity of the DDAB film, 2K + K ; is close to 1.0k B T . This means that rather
      than acting as an effective parameter in the SANS analysis, the polydispersity is
      a natural consequence of the film rigidity. These results show that the film
      bending energy model accounts well for the behavior of such DDAB microemulsions.

PMID- 9241189
TI  - The Effect of Fluctuations on Bilayer and Monolayer Systems: High-Resolution X
      ray Scattering Study of a Three-Component Lamellar Phase
AB  - We have investigated the effect of symmetry on the fluctuation of a three
      component lamellar phase composed of oil (octane), water, and a nonionic
      surfactant (C12E5). The studied lamellae consist of various oil/water volume
      ratios for a fixed surfactant concentration. From aligned lamellae, we succeeded
      in obtaining highly reproducible, high-resolution X-ray spectra with very small
      full width at half maximum (6 x 10(-4) A-1 ). The deviation of the periodicity
      expected by the dilution law can be explained from the fluctuations. Measuring
      this deviation, we observed that for the constant surfactant concentration,
      lamellae with equal oil/water ratios have higher fluctuation than when oil/water 
      -> 0 or infinity because of the difference of the flexibility of monolayers and
      bilayers

PMID- 9241190
TI  - Counterion Exchange Selectivity in Detergent-Polymer Aggregates
AB  - In aqueous solution, the interaction between sodium dodecyl sulfate (SDS) and
      poly(ethylene glycol) (PEG) results in the formation of small aggregates or
      clusters of SDS attached to the PEG polymer chain. Selectivity coefficients for
      exchange of two monovalent (N -methyl-4-cyanopyridinium cation and Tl+ ) and two
      divalent (methylviologen cation and Cu2+ ) counterions at the surface of SDS-PEG
      clusters, determined employing photophysical techniques, are similar, but not
      identical, to those for exchange at the surface of SDS micelles in the absence of
      PEG. The principal factor affecting ion exchange selectivity in SDS-PEG clusters
      does not appear to be aggregate size or surface charge density but rather the
      presence of poly(oxyethylene) subunits at the aggregate surface.

PMID- 9241191
TI  - Effect of Electrode Pattern on the Column Structure and Yield Stress of
      Electrorheological Fluids
AB  - For electrorheological (ER) suspensions, the aggregate structures of particles
      were observed in electric fields by the use of transparent cells with different
      electrode patterns. Although the suspension is dispersed to noninteracting
      particles without electric fields, many aggregates are formed on the electrode
      surface in electric fields. Since the dipole-dipole interactions cause chain
      structures of particles and equilibrium conformations of chains are always
      aligned with electric field, the aggregates indicate the presence of columns
      spanning the electrode gap. The particle concentration in columns which are
      developed between parallel-plate electrodes is about 22 vol %. In striped
      electrodes, the particles construct striped aggregates along the electrodes and
      no particles remain in the insulating region. The particle concentration in
      striped aggregates is about 35 vol %. The nonuniformity of electric field is
      responsible for the high particle concentration. The increase in particle
      concentration of column lead to the high yield stress of electrified suspension.
      Therefore, the ER performance of suspension as an overall response can be
      improved by the electrode design.

PMID- 9241192
TI  - Enthalpy of Adsorption and Isotherms for Adsorption of Naphthenic Acid onto Clays
AB  - The enthalpies of adsorption and the isotherms for adsorption of naphthenic acid
      onto Na-montmorillonite, Na-kaolinite, and Na-illite were studied by means of
      calorimetry and the static method at 298.15 K. The results show that the
      enthalpies of adsorption and saturated adsorption amounts of naphthenic acid on
      different clays change in the order Na-montmorillonite > Na-illite > Na
      kaolinite. The interaction between naphthenic acid and clays is discussed.

PMID- 9241193
TI  - Interactions between Adsorbed Layers of a Low Charge Density Cationic
      Polyelectrolyte on Mica in the Absence and Presence of Anionic Surfactant
AB  - Interactions between two negatively charged mica surfaces across aqueous
      solutions containing various amounts of a 10% charged cationic polyelectrolyte
      have been studied. It is found that the mica surface charge is neutralized when
      the polyelectrolyte is adsorbed from a 10-50 ppm aqueous solution. Consequently
      no electrostatic double-layer force is observed. Instead an attractive force acts
      between the surfaces in the distance regime 250-100 A. We suggest that this
      attraction is caused by bridging. Additional adsorption takes place when the
      polyelectrolyte concentration is increased to 100 and 300 ppm, and a long-range
      repulsion develops. This repulsive force is both of electrostatic and steric
      origin. The polyelectrolyte layer adsorbed from a 50 ppm solution does not desorb
      when the polyelectrolyte solution is replaced with an aqueous polyelectrolyte
      free solution. Injection of sodium dodecyl sulfate (SDS) into the measuring
      chamber to a concentration of about 0.01 CMC (8.3 x 10(-5) M ) does not affect
      the adsorbed layers or the interaction forces. However, when the SDS
      concentration is increased to 0.02 CMC (0.166 mM ) the adsorbed layer expands
      dramatically due to adsorption of SDS to the polyelectrolyte chains. The sudden
      swelling suggests a cooperative adsorption of SDS to the preadsorbed
      polyelectrolyte layer and that the critical aggregation concentration between the
      polyelectrolyte and SDS at the surface is about 0.02 CMC. The flocculation
      behavior of the polyelectrolyte in solution upon addition of SDS was also
      examined. It was found that 0.16-0.32 mol SDS/mol charged segments on the
      polyelectrolyte is enough to make the solution slightly turbid.

PMID- 9241194
TI  - Ozone Degradation by Fluoride onto Plasma-Treated Activated Carbon in CF4
AB  - The ozone degradation of fluorine was investigated using the tetrafluoromethane
      plasma-treated activated carbon (PT-AC). The ozone in the stratosphere has been
      degraded by the chloride and bromide radicals which are produced from
      chlorofluorocarbons and bromofluorocarbons, respectively. However, we believe
      that fluorine also was related to the ozone degradation. The fluoride was
      introduced onto the activated carbon surface by tetrafluoromethane plasma
      treatment. The breakthrough curve of ozone onto PT-AC was measured to elucidate
      the relationship between the ozone and the fluoride. The amount of ozone
      adsorbed/degraded onto the PT-AC was larger than the amount that was
      adsorbed/degraded onto the untreated activated carbon. The amount of fluoride ion
      eluted from the PT-AC before the adsorption/degradation of ozone was larger than
      that which eluted after the adsorption/degradation of ozone. These results
      indicated that the ozone was degraded by the fluoride on the PT-AC surface.

PMID- 9241195
TI  - Adsorption and Recovery of Ionic Surfactants by beta-Cyclodextrin Polymer
AB  - The adsorption and recovery of ionic surfactants, such as dodecylbenzenesulfonic
      acid (DBS) and benzalkonium chloride (BKC), from an aqueous solution were studied
      using the beta-cyclodextrin polymer (beta-CDP). BKC always demonstrated a higher
      adsorption efficiency than DBS in batch tests, isotherms, and column tests. The
      adsorption characteristics of the surfactants seemed to be caused by inclusion
      into beta-CD, and they were easily determined using the Langmuir adsorption
      isotherm. Furthermore, the surfactants adsorbed by beta-CDP were easily released
      by shaking it with a mixture of water and methanol. Recovery efficiency was
      dependent on the mixture ratio of the solvent, and regenerated beta-CDP was
      reusable as an adsorbent.

PMID- 9241196
TI  - Effect of Neck Formation on the Measurement of Dynamic Interfacial Tension in a
      Drop Volume Tensiometer
AB  - Dynamic interfacial tension values obtained by drop volume tensiometry will be
      affected under certain experimental conditions by the formation of a neck between
      the drop and the capillary tip. This phenomenon must be accounted for to obtain
      accurate values of interfacial tension. In this work, neck formation for a water
      mineral oil system is studied under conditions where hydrodynamic effects can be
      neglected. A model originally developed for the determination of the surface
      tension of a suspended drop is modified for application to dynamic interfacial
      tensions of surfactant-containing liquids. The model relates apparent values of
      interfacial tension calculated from drops possessing necks to actual values.
      Experiments with Span 80 (sorbitan monooleate) and sodium dodecyl sulfate (SDS)
      surfactants in a mineral oil-water system are used to test the validity of the
      developed model. For the small tip diameter used, good agreement is obtained for
      Span 80 up to the critical micelle concentration, and for low concentrations of
      SDS, when the surfactant adsorption is diffusion-limited. In both cases, the neck
      diameter of the growing drop can be considered constant over the range of dynamic
      interfacial tensions tested.

PMID- 9241197
TI  - Long Lifetime Floating Drops
AB  - Using a rotating magnet device, we observe the noncoalescence of droplets of
      certain liquids slightly put in contact with the surface of the same liquid. The
      droplets go into the vortex and coalesce, the resulting drop staying in
      equilibrium in this position. If the rotation of the liquid is stopped, the drop
      rests at the surface for more than 20 s, as if it were immiscible, without any
      relative motion.

PMID- 9241198
TI  - Influence of Substrate Hydrophobicity on the Adsorption of Collagen in the
      Presence of Pluronic F68, Albumin, or Calf Serum
AB  - The influence of Pluronic F68 [a poly(ethylene oxide)-poly(propylene oxide)
      poly(ethylene oxide) copolymer surfactant], serum albumin (HSA), and fetal calf
      serum (FCS) on the adsorption of type I collagen by polymer substrates was
      investigated using radiolabeling and XPS analysis. Three different kinds of
      polystyrene substrates with increasing level of hydrophobicity were used. Change
      in the state of hydration of the sorbent and protein surfaces appears to be the
      main driving force for collagen adsorption. Pluronic F68 strongly reduces
      collagen adsorption, the reduction being more pronounced with higher substrate
      hydrophobicity. This explains why epithelial cell adhesion on substrates
      preconditioned with a solution of Pluronic F68 and collagen is strongly
      influenced by substrate hydrophobicity. Collagen adsorption is also reduced in
      the presence of HSA and FCS, but the reduction and its sensitivity to substrate
      hydrophobicity are lower than with Pluronic F68.

PMID- 9241199
TI  - The Effect of Diameter Ratio and Volume Ratio on the Viscosity of Bimodal
      Suspensions of Polymer Latices
AB  - Previously, the rheological properties of different sized monodisperse polymer
      latices of polystyrene and polymethyl methacrylate (PMMA) were determined. This
      paper describes procedures in which carefully prepared blends of the same
      monodisperse latices were mixed together to examine the effect of the differences
      in size between the latices (diameter ratio) on the rheology of the blend. The
      relative viscosities of these blends were then measured as a function of the
      total volume fraction and compared with those of the constituent parts. In a
      bimodal suspension, theory predicts that a maximum packing fraction and hence a
      minimum viscosity is achieved with 27% small particles by volume. The experiments
      revealed that a minimum viscosity was obtained with 25% small particles by volume
      and with a diameter ratio of 7.83. At this diameter ratio, the small particles
      are able to pass through the triangular pore between the large particles and this
      essentially leads to an increased maximum packing fraction of the suspension.
      Hence the suspension will have a lower viscosity. Other diameter ratios at 25%
      small particles by volume that led to suspensions with lower viscosities were
      4.03, 6.37, and 11.15. On the other hand the suspensions with diameter ratios of
      2.81 and 5.67 led to increases in viscosity. This is a result of the small
      particles being too big to fit in the gaps between the large particles. All the
      other diameter ratios at all the other compositions (i.e., 50 and 75% small
      particles by volume) resulted in viscosities higher than that obtained for the
      monodisperse polystyrene latex. These effects may be explained by changes in the
      value of the maximum packing fraction. An increased maximum packing fraction of
      the system leads to lower viscosities and vice versa. The results challenge the
      conventional view that simply increasing the diameter ratio at a fixed
      composition leads to reduced viscosities and increased maximum packing fractions.
      This simple picture does not appear to hold for binary suspensions of colloidal
      particles at every particle size ratios.

PMID- 9241200
TI  - Predictive Model for the Calculation of Interfacial Tension in Nonideal
      Electrolytic Systems
AB  - A new model is proposed for the calculation of the interfacial tension between an
      organic solvent and concentrated aqueous solutions of electrolytes. The
      interfacial tension is derived from the isothermal Gibbs equation. The increase
      or decrease of interfacial tension with concentrations are modeled using a
      Langmuir-type adsorption equation and the strong non-ideality of the mixtures is
      taken into account through the Mikulin equation. The model parameters are first
      determined with binary water-electrolyte solutions and are kept constant in the
      case of mixtures. The model has been applied to chloride solutions-chloride salts
      of various metals and hydrochloric acid-and compared with experimental data
      obtained by using the pendant drop technique and a Wilhelmy tensiometer. In all
      cases investigated, good agreement is observed, even in the case of stiff
      variations of interfacial tension with the electrolyte concentration and also at
      high concentrations of electrolytes.

PMID- 9241201
TI  - Dynamic Interfacial Tensions of Aqueous Triton X-100 Solutions in Contact with
      Air, Cyclohexane, n -Heptane, and n -Hexadecane
AB  - Measurements of the dynamic interfacial tensions of aqueous Triton X-100
      solutions in contact with air, cyclohexane, n -heptane, and n -hexadecane were
      performed with the drop-volume method using different flow rates for subsequently
      falling drops. In the longer time range the plots of the dynamic interfacial
      tension versus 1/ radicalt show linear dependence in all four cases. Additional
      equilibrium surface tension measurements with the Wilhelmy-plate technique were
      performed at the interface to air. Equilibrium results from the Wilhelmy-plate
      measurements and dynamic data extrapolated to t --> infinity at the interface to
      air coincide well. The extrapolated data from dynamic investigations were used to
      calculate the maximum adsorption of Triton X-100 via the Gibbs equation at the
      four interfaces. In order to calculate the equilibrium adsorption at a specific
      bulk phase concentration the Langmuir-Szyskowski equation was used and from the
      data it was possible to calculate effective diffusion coefficients via a long
      time approximation of the Ward and Tordai equation. The resulting amounts of
      adsorbed surfactant at the four interfaces show acceptable values. The calculated
      diffusion coefficients at the water/air interface are in the right order of
      magnitude. For the interfaces to oil the effective diffusion coefficients are
      smaller due to the solubility of Triton X-100 in the oil phases. Additionally the
      distribution coefficients between water and the oil phases for Triton X-100 are
      given.

PMID- 9241202
TI  - Interactions between Tristearin Crystals and Proteins at the Oil-Water Interface
AB  - A Couette-type torsion wire surface shear viscometer was used to measure the
      apparent interfacial shear viscosity of pH 7 (I = 0.05 M ) buffered solutions of
      lysozyme, sodium caseinate, and Tween-40 in contact with either n -tetradecane or
      purified sunflower oil at a planar interface. When proteins were present in the
      aqueous phase and tristearin crystals in the oil phase, there was a synergistic
      increase in the interfacial shear viscosity over the sum of each component in the
      absence of the other. The magnitude of the increase appeared to be independent of
      the type of protein but dependent on the nature of the oil phase. This increase
      in the interfacial shear viscosity was found not to be due simply to the protein
      reducing the interfacial tension and thus affecting the adsorption behavior of
      the fat crystals. When the aqueous phase contained a small-molecule surfactant
      (Tween-40) instead of protein, but at the same interfacial tension as the sodium
      caseinate system, a significantly smaller increase was observed in the
      interfacial shear viscosity than in the protein system. It therefore seems likely
      that when proteins are present, hydrophobic peptide residues interact with the
      tristearin crystals at the interface.

PMID- 9241203
TI  - A Novel Numerical Analysis on Surface Charge Densities of an Amphoteric O/W-Type
      Microemulsion in the Presence of CaCl2 and/or AlCl3
AB  - The effect of pH on the surface charge density of the O/W-type microemulsion
      formed in solutions of an amphoteric surfactant, (N alpha , N alpha -dimethyl-N
      epsilon -lauroyllysine, DMLL)/n -octane/1-pentanol/CaCl2 or AlCl3 , has been
      investigated. A novel equation for the surface charge densities in the presence
      of a multivalent cation (Ca2+ and/or Al3+ ) has been derived taking account of
      the number of DMLL molecules bound to a multivalent cation (q ). By applying a
      numerical analysis of this equation, it is possible to determine the intrinsic
      binding constants (K ) of the multivalent cation and the monovalent anion to the
      hydrophilic groups of DMLL and the adsorption density (N ) of DMLL molecules on
      the oil/water interface. Furthermore, N has been found to show pH dependence. N
      has a maximum value around the isoelectric region (in particular, pH 5-7) of DMLL
      molecules in the presence of CaCl2 , whereas N increases with increasing pH in
      the presence of AlCl3 . The surfactant (DMLL) numbers per O/W-type microemulsion
      droplet, i.e., the aggregation numbers, are successfully obtained as a function
      of pH in the presence of CaCl2 and/or AlCl3 .

PMID- 9241204
TI  - Micellar Effects on the Reaction S2 O8 2- + Fe(CN)4 (bpy)2-
AB  - The reaction Fe(CN)4 (bpy)2- + S2 O8 2- has been studied in aqueous solutions of
      hexadecyltrimethylammonium chloride (CTAC) and bromide (CTAB), sodium dodecyl
      sulfate (SDS), dodecyl tricosaoxyethylene glycol ether (Brij35 ), and
      octylphenol(ethyleneoxide)9.5 ether (Triton X-100). The influence of changes in
      surfactant concentration on the reaction rate has been investigated. Experimental
      kinetic data show that the reaction rate is not affected by the presence of SDS,
      Brij35 , and Triton X-100 in the reaction medium within the surfactant
      concentration range studied. In CTAC and CTAB solutions the observed first order
      rate constant is much higher than that obtained in pure water, which can be
      explained by considering that the two anionic reactants are localized at the
      positively charged micellar surface. This is also in agreement with the observed
      decrease in the reaction rate when [cationic surfactant] increases. An increase
      in the surfactant concentration would provoke a decrease in the local
      concentration of the reagent in excess, S2 O8 2- ions, at the micellar surface,
      that is, at the reaction site, which would result in a decrease of the observed
      pseudo-first-order rate constant. Temperature was maintained at 298.2 K.

PMID- 9241205
TI  - Dissolution of a Drop on a Liquid Surface Leading to Surface Waves and
      Interfacial Turbulence
AB  - If a droplet of liquid with a lower surface tension than that of water and
      partially soluble in water is deposited on a free water surface, it spreads,
      dissolves, and simultaneously creates surface tension gradients leading to
      Marangoni instability and interfacial turbulence. In a first stage, if the
      solubility of the drop is not too high, there is formation of patterns that
      evolve in time, eventually leading to interfacial turbulence and droplet
      disappearance. These patterns, which on occasion last quite long time intervals,
      result from the interaction and collision of surface waves sustained by the
      surface tension gradient. These surface waves have been observed with a Schlieren
      device and their characteristics (e.g., shape, velocity) have been measured. Two
      types of surface wave profiles exist: wave profile like a "hump" (sech-like) or
      like a hydraulic jump (tanh-like). We have followed their time evolution and for
      head-on, oblique, and overtaking collisions we have measured their trajectories.
      We have been able to correlate our experimental findings with available
      theoretical, albeit qualitative, results known about waves and shocks.

PMID- 9241206
TI  - The Theory of Thermodynamics for Chemical Reactions in Dispersed Heterogeneous
      Systems
AB  - In this paper, the expressions of Gibbs energy change, enthalpy change, entropy
      change, and equilibrium constant for chemical reactions in dispersed
      heterogeneous systems are derived using classical thermodynamics theory. The
      thermodynamical relations for the same reaction system between the dispersed and
      the block state are also derived. The effects of degree of dispersion on
      thermodynamical properties, reaction directions, and chemical equilibria are
      discussed. The results show that the present equation of thermodynamics for
      chemical reactions is only a special case of the above-mentioned formulas and
      that the effect of the dispersity of a heterogeneous system on the chemical
      reaction obeys the Le Chatelier principle of movement of equilibria.

PMID- 9241207
TI  - Adsorption of a Hard Sphere Fluid in a Disordered Polymerized Matrix: Application
      of the Replica Ornstein-Zernike Equations
AB  - A model of hard spheres adsorbed in disordered porous media is studied using the
      associative replica Ornstein-Zernike (ROZ) equations. Extending previous studies
      of adsorption in a hard sphere matrices, we investigate a polymerized matrix. We
      consider an associating fluid of hard spheres with two intracore attractive sites
      per particle; consequently chains consisting of overlapping hard spheres can be
      formed due to the chemical association. This is the generalization of the model
      with sites on the surface of Wertheim that has been studied in the bulk by Chang
      and Sandler. The matrix structure is obtained in the polymer Percus-Yevick
      approximation. We solve the ROZ equations in the associative hypernetted chain
      approximation. The pair distribution functions, the fluid compressibility, the
      equation of state and chemical potential of the adsorbed fluid are obtained and
      discussed. It is shown that the adsorption of a hard sphere fluid in a matrix at
      given density, but consisting of longer chains of overlapping hard spheres, is
      higher than the adsorption of this fluid in a hard sphere matrix.

PMID- 9241208
TI  - Effect of Acids on Water Vapor Uptake by Pyrogenic Silica
AB  - Effect of gaseous HCl and HNO3 on the water vapor uptake by pyrogenic silica was
      studied at different relative humidities (RH) for pure water and different
      compositions of binary and ternary vapor mixtures. Experiments showed that the
      ability of silica to uptake water strongly depends on RH and on the type of acids
      and their concentration in the vapor mixtures. At low acid concentration in the
      binary mixtures the influence of acids is probably small. Water uptake by silica
      does not change monotonically with acid concentration: at first it decreases and
      then starts to grow. However, the presence of acids promotes water uptake, and
      the effect is very significant at low RH. HCl seems to be more effective acid to
      enhance water uptake than HNO3 . In the case of ternary mixtures the adsorbed
      weight of water is a bit larger than that adsorbed from the binary mixtures.
      Acids are accumulated by silica surface, and the accumulation is larger for
      nitric acid.

PMID- 9241209
TI  - Direct Measurement of Colloidal Forces between Mica and Silica in Aqueous
      Electrolyte
AB  - A refined methodology which allows attachment of submicrometer colloidal
      particles to atomic force microscopy cantilevers is described. The interactions
      between particles of this size and both mica and silica surfaces in aqueous
      electrolyte at pH 5.8 have been studied. The monotonic repulsive force observed
      was in all cases well fitted by assuming that the force was due to overlap of
      electrical double layers. The potential of a cleaved mica surface was found to be
      significantly less than that of the silica surface. However, the mica potential
      was found to increase, if the mica surface was immersed immediately (within
      seconds) in electrolyte after cleavage or after plasma cleaning. This behavior is
      explained by the finite aqueous solubility of adventitious carbon that
      spontaneously deposits on mica after cleavage in air. The surface potential of
      the silica spheres was obtained by fitting symmetric interaction data. The trend
      in zeta potential of the silica spheres with pH, determined by particle
      electrophoresis, was similar to that obtained from analysis of force-separation
      data.

PMID- 9241210
TI  - Simulated Contact Angle Hysteresis of a Three-Dimensional Drop on a Chemically
      Heterogeneous Surface: A Numerical Example
AB  - A public domain software package is employed in the quasi-steady-state simulation
      of contact angle hysteresis. Three-dimensional sessile drops in equilibrium with
      a model chemically heterogeneous smooth solid surface are considered; evolving
      drop shapes, as a function of incremental changes in their volume, are
      investigated. Results are presented for a model system in which the intrinsic
      contact angle is assumed to vary along the surface in a periodic manner.
      Throughout the simulation, calculated contact angles show reasonable agreement
      with the local intrinsic contact angle values, and the computed drop shapes are
      found to be constant mean curvature surfaces. Significant hysteresis in the
      liquid-fluid interface curvature and average contact angle is found; a complete
      hysteresis loop is simulated. Advancing and receding contact angles exhibit the
      "stick-slip" behavior observed in experiments as well as in previous 2-D
      simulations.

PMID- 9241211
TI  - Hysteresis Phenomena in the Study of Sorptive Deformation of Sorbents
AB  - A combined experimental approach comprising up-to-date high-sensitivity methods
      was used to reveal the factors causing the sorptive hysteresis that occurs in
      sorption. The dilatometric method was used for the first time to study the
      sorptive deformation hysteresis of sorbents. On the basis of the results
      obtained, it was suggested that sorbent deformation may be the universal cause of
      sorptive hysteresis.

PMID- 9241212
TI  - Extremely Strong Interaction of Sodium Decyl Sulfate and Decyltrimethylammonium
      Bromide in Molecular Aggregates
AB  - The thermodynamic behavior of a mixture of sodium decyl sulfate (SDeS) and
      decyltrimethylammonium bromide (DeTAB) in aqueous solution and in molecular
      aggregates such as surface adsorbed films and micelles was investigated by
      measuring the electric conductivity and surface tension of the aqueous solutions.
      The thermodynamic quantities in solution and those in the molecular aggregates
      were evaluated from the experimental conductivity and surface tension data. The
      results for molar conductivity showed that dimerization or ion-pair formation of
      the SDeS and DeTAB molecules does not occur in aqueous solution and the mixture
      behaves as uni-univalent strong electrolyte below the critical micelle
      concentration (CMC). Contrary to the results in the aqueous solution, we found
      significant nonideal behavior in the phase diagrams of surface adsorption; that
      is, equimolar mixture of SDeS and DeTAB exists in the adsorbed film at almost all
      compositions irrespective of the bulk composition in the solution. The same
      result was also observed in the phase diagram of micelle formation. There was no
      difference in phase diagrams between surface adsorption and micelle formation at
      the CMC. The great nonideal mixing of SDeS and DeTAB in the molecular aggregates
      is undoubtedly attributable to the extreme attractive interaction between
      oppositely charged polar head groups of surfactants as well as to cohesion
      between hydrophobic groups. Further, in a low concentration region, it turned out
      that equimolar composition is preserved in the film during phase transition of
      the mixed adsorbed film of SDeS and DeTAB from a gaseous state to an expanded
      state.

PMID- 9241213
TI  - Effects of Functionalized Latex Particles and Anionic Surfactants on the Flow
      Behavior of Aqueous Gelatin Dispersions
AB  - The flow behavior of aqueous gelatin dispersions containing latex particles with
      different surface characteristics is studied as a function of the concentration
      of anionic surfactants. The work describes the nature and strength of
      interactions occurring in the system. The study of the effects of individual
      components may help to gain information on the flow behavior of commercial
      photographic color coupler dispersions. Due to interactions with the gelatin, the
      flow behavior of a dispersion of latex particles in 4.6% (w/w) aqueous gelatin
      solution depends strongly on charge and surface characteristics of the particles.
      For hard particles with nonionic hydrophilic shells, the flow behavior can be
      described by the theory of hard spheres. If anionic surfactants such as sodium i 
      dodecylbenzenesulfonate (DBS) or sodium di-sec -butylnaphthalenesulfonate (BXG)
      are added, the rheological behavior is mainly determined by the interactions
      between the gelatin and the surfactants in the continuous phase. If soft
      particles with ionic shells are dispersed in the aqueous gelatin, the viscosity
      is more strongly increased than predicted by the hard sphere model. Upon further
      addition of a surfactant, the primarily pseudoplastic flow behavior becomes more
      and more Newtonian, presumably due to depletion of originally surface-adsorbed
      gelatin molecules. The stabilization of the latex is changed from steric to
      electrostatic. If large amounts of surfactant are added, depletion flocculation
      is most likely to occur. A model of the gelatin-latex-surfactant interactions is
      presented which takes into account the surface characteristics of the particles.

PMID- 9241214
TI  - Effect of Cross-Linking on the Dewetting of an Elastomeric Surface
AB  - It has been shown over the last few years how the wetting (or dewetting) of a
      soft, elastomeric substrate can be markedly affected by local deformation of the
      solid near the triple line, due to the component of liquid surface tension acting
      perpendicularly to the (undeformed) solid surface, i.e., the "wetting ridge."
      Since the degree of cross-linking of an elastomer affects its mechanical
      properties, we have undertaken a study of the influence of cross-linking on
      (de)wetting behavior. Using a silicone rubber in four states of cross-linking, we
      have observed that triple-line motion of tricresyl phosphate increases in speed
      with degree of cross-linking. Two principal factors influence this behavior, both
      being directly linked to average intercross-link molecular weight, M c . A
      decrease in M c increases elastic modulus and therefore decreases the importance
      of the wetting ridge, whilst also lowering the dissipative properties of the
      polymer. The combined effects lead, in the case studied, to a linear relationship
      between dewetting speed and elastomeric elastic modulus to the power 10/3.

PMID- 9241215
TI  - Thermodynamic Study on the Surface Formation of the Mixture of Water and Ethanol
AB  - The formation of the water + ethanol mixture/air surface was studied by measuring
      the surface tension as a function of temperature and the mole fraction of ethanol
      in the mixture. The surface composition, the entropy Deltas , and energy Deltau
      of surface formation were evaluated by adopting the thermodynamic equations. It
      was shown that the surface was enriched in ethanol molecules compared with the
      bulk solution. The values of Deltas and Deltau were examined closely by
      estimating the contribution from the nonideal mixing in the bulk solution and
      that at the surface to Deltas and Deltau . It was concluded that the surface
      formation is driven by entropy at lower x 2 and by energy at higher x 2 ,
      respectively, and that the surface formation becomes more energetically favorable
      with rising temperature.

PMID- 9241216
TI  - Use of Nitroxides as Topological Monitors of the Interaction of Silica-Based
      Particles with Components of the Biological Environment
AB  - The interaction of solid particles, such as silica and vitreous fibers, with
      different surrounding media which well mimic the various environments in a
      biological medium, such as inhaled in vivo or in a cell culture, has been studied
      by means of the electron paramagnetic resonance (EPR) spectra of spin labels
      attached to the solid surface or spin probes inserted in the surrounding medium.
      Among the solid particles, a MCM-41 type mesoporous silica was found to be very
      suitable for investigating the binding between the labels and different
      molecules, due to the high surface area and the availability of interacting sites
      in the internal channels of the structure. The computer-aided analysis of the
      spectral lineshape allowed the evaluation of structural and dynamic parameters. A
      model has been proposed which describes the interactions of the solid surface
      with: (a) pure solvents at different polarities; (b) molecules present in
      biological fluids, which mimic the effect of physiological solutions; (c) the
      components of the cell membrane (phospholypid or proteins in water solution); and
      (d) a model phospholypid membrane, to mimic the interaction between the solid
      particles and the cell membrane. The hydration of the surface lets the labels
      interact preferentially with the water molecules with respect to the surface
      itself, or the other labels. Apolar molecules decreased the mobility of the
      labels attached to the surface. Phospholipid bilayers were formed at the solid
      surface, whose internal structure was more fluid with respect to noninteracting
      bilayers, whereas the external polar groups trapped probe and label molecules in
      restricted space at the surface. The labels were partially extracted from the wet
      surface of the vitreous fibers by the interaction with a protein (albumin) and
      distributed in two different environments (at different polarities).

PMID- 9241217
TI  - Rheology of Sodium Caseinate Stabilized Oil-in-Water Emulsions
AB  - We report on shear rheological measurements at 30&deg;C of fine oil-in-water
      emulsions (volume-surface average diameter < 0.5 &mgr;m) prepared at pH 6.8 with
      sodium caseinate as the sole emulsifier (1-6 wt%) and n -tetradecane as the
      dispersed phase (10, 35, or 45 vol%). Strong sensitivity of rheological behavior
      to total protein concentration was indicated by both steady-state viscometry and
      small-deformation oscillatory experiments. The behavior can be classified into
      three types, depending on the protein/oil ratio. (1) Emulsions containing
      insufficient protein for (near-) saturation protein surface coverage develop a
      time-dependent increase in low-stress apparent viscosity and associated shear
      thinning behavior; this can be attributed to bridging flocculation. (2) Emulsions
      having full protein surface coverage but relatively little excess unadsorbed
      protein in the continuous phase are stable Newtonian liquids. (3) Emulsions
      containing a substantial excess of unadsorbed sodium caseinate exhibit
      considerable pseudoplasticity which can be attributed to depletion flocculation.
      Taken as a whole, the time-dependent rheological properties for this set of
      emulsions as a function of protein content and oil volume fraction are largely
      consistent with our previous results on the creaming stability and the particle
      gel microstructure for these same emulsion systems. In particular, the reversible
      flocculation of emulsion samples of high protein content is readily explicable in
      terms of depletion flocculation of droplets by unadsorbed protein existing in the
      form of approximately spherical caseinate submicelles.

PMID- 9241218
TI  - The Promotion of Alkaline Fading of Crystal Violet by AOT Micelles Dispersed in
      Supercritical Ethane Medium
AB  - The alkaline fading of crystal violet (CV) is accelerated by using a w/o
      microemulsion of H2 O/AOT/ethane under supercritical conditions. The rate of
      fading can be changed by three orders of magnitude with the molar ratio of water
      to AOT and operating pressure. The highest rate of CV fading observed is larger
      by a factor of 100 or more compared to those reported so far in the literature.
      The structure of AOT molecules and the type of interior water molecules seem to
      account for the rate enhancement with an increase in the water/AOT molar ratio.
      It is suggested that the intermicellar and AOT-ethane interactions are of
      significance for the promotion effect of pressure.

PMID- 9241219
TI  - Drainage and Coalescence in Standing Foams
AB  - A theoretical model is presented for the drainage, collapse, and coalescence in
      standing foams. The foam is assumed to consist of pentagonal dodecahedra and
      coalescence is assumed to occur due to a variation in the sizes of the films
      which constitute the faces of these polyhedra. Even in a monodispersed foam
      containing bubbles having the same volume, the film areas are not identical, but
      are distributed randomly about a mean. This leads to a nonuniformity of film
      drainage rates and hence of film thicknesses within any volume element in the
      foam. Smaller films drain faster and rupture earlier, causing the bubbles
      containing them to coalesce. The evolution of coalescence is monitored via the
      mean bubble volume which varies in the vertical direction. The model is also able
      to predict the evolution of the surfactant concentration profile as it changes
      due to coalescence and collapse. Simulations are performed to examine the effect
      of various parameters, such as the apparent diffusion coefficient of the
      surfactant, the distribution of film sizes, and the concentrations of surfactant
      and salt in the foaming solution on the drainage and collapse behavior of the
      foam.

PMID- 9241220
TI  - Adsorption of n -Dodecyl-beta-d -maltoside on Solids
AB  - Adsorption of a typical sugar-based surfactant, n -dodecyl-beta-d -maltoside
      (DM), on hydrophilic solids, silica, alumina, titania, and hematite, and a
      hydrophobic solid, graphite, was studied. Effects of salts and pH on the
      adsorption on alumina as well as the electrokinetic potential of the particles
      after surfactant adsorption were studied to determine the adsorption mechanisms.
      Hydrophobicity and settling rate were measured to explore the surfactant
      conformation on the particle surfaces. For hydrophilic solids, DM was found to
      adsorb strongly on alumina, titania, and hematite but weakly on silica. While
      hydrogen bonding is postulated to be the major driving force for the adsorption
      on hydrophilic solids, for hydrophobic solid, the adsorption is mainly due to the
      hydrophobic interactions. The different behaviors of surfactant on hydrophilic
      and hydrophobic solids were attributed to the different interactions between
      surfactant and solids. Also, the surfactant is estimated to form a bilayer on
      alumina while on graphite it forms a monolayer. The surface hydrophobicity and
      stability of the solids are discussed in terms of the adsorbed monolayer/bilayer
      formation on the particles.

PMID- 9241221
TI  - Modification of SiO2 Surfaces by Reaction with Acetals, Ketals, Orthoesters, and
      Orthocarbonates
AB  - SiO2 was treated with compounds of the type C(OR)4 (orthocarbonates), R'C(OR)3
      (orthoesters), and R'R"C(OR)2 (acetals and ketals) in CCl4 under reflux. The
      resulting modified surfaces were analyzed with IR, 1 H NMR, and 13 C NMR
      spectroscopy, and TGA. The initial compounds decompose, leaving on the surface
      only OR groups that are tightly bound. The reaction with orthocarbonates and
      orthoesters is more effective than that with acetals or ketals, and the SiO2
      surface can be covered with OR groups to a high degree. The adsorption of
      polymers is restricted by the bound organic species. The modified surfaces are
      similar in many respects to those of alcohol-treated silicas, but the reaction
      proceeds at lower temperatures than those typically used for silica modification
      with alcohols.

PMID- 9241222
TI  - A Study of the Adsorption of Acrylic Acid and Maleic Acid from Aqueous Solutions
      onto Alumina
AB  - The adsorption of acrylic acid and maleic acid on alumina was studied, and it has
      been found that the adsorption obeys the Langmuir isotherm. The adsorption of the
      acids is dependent on the pH of the solutions. For acrylic acid, the optimal pH
      is 4.5; for maleic acid, the optimal pH is 1.1-1.6. These pH values are close to
      the pKa for acrylic acid and pKa 1 for maleic acid, respectively. The maximum
      amount of each acid adsorbed at its optimal pH was obtained by fitting the
      adsorption data to the Langmuir isotherm, and the values are 727 &mgr;mol/g for
      acrylic acid and 525 &mgr;mol/g for maleic acid. These values are consistent with
      monolayer adsorption. Solid state 13 C NMR was used to investigate the nature of
      the adsorption. It is suggested that the adsorbed carboxylic acids are present in
      the undissociated form.

PMID- 9241223
TI  - Heteroenergetics of Bovine Serum Albumin Adsorption from Good Solvents Related to
      Crystallization Conditions
AB  - Total internal reflection fluorescence (TIRF) was applied to study adsorption of
      bovine serum albumin (BSA) from a thermodynamically good solvent commonly used as
      a buffer for BSA crystallization. BSA adsorption is shown to exhibit
      heteroenergetics, which is possibly a general property of protein interfacial
      behavior. For example, BSA adsorption on quartz, SnO2 , and alkyl-modified
      surfaces demonstrates broad continuous distributions of energies of adsorption
      activation and protein-surface binding. For heteroenergetic adsorption, the type
      of the isotherm and kinetics depends on the type of the energy distribution
      functions and the type of correlation between the energies. In the case of BSA
      adsorption on quartz and SnO2 surfaces, protein interfacial behavior is
      consistent with a model suggesting rectangular distributions both of activation
      energies of adsorption and energies of protein-surface binding. In the case of an
      alkyl-modified surface, BSA adsorption kinetics is interpreted in terms of a
      heteroenergetic model suggesting initial adsorption at selected adsorption sites
      with maximum rate constants. The model also suggests that lateral diffusion
      quickly redistributes the molecules from the initial adsorption sites to the
      sites with higher binding energies. The combination of TIRF spectroscopy with an
      electrochemical system was used to study the effect of surface charge on protein
      adsorption on a transparent SnO2 electrode. BSA behavior on the SnO2 electrode
      was found to correlate with surface hydrophobicity and indifferent to charges
      both of the surface and the protein. Hydrophobic interactions seem to be the
      principal driving force in determining the behavior of BSA at the solid-liquid
      interface and likely plays an important role in protein crystallogenesis.

PMID- 9241224
TI  - Effect of Nonadsorbing Polyelectrolytes on Colloidal Interactions in Aqueous
      Mixtures
AB  - The effect of adding a nonadsorbing charged polymer, sodium polystyrene sulfonate
      (SPSS), on the interaction energy profile between a 15 &mgr;m diameter
      polystyrene particle and a glass plate was measured using the optical technique
      of total internal reflection microscopy. A typical profile consisted of a
      repulsive barrier at large separations followed by a secondary well. Evidence of
      a longer-range tertiary well was also observed in salt-free solutions where the
      polymer molecules are rod-like. Addition of electrolyte causes a reduction in the
      depth of the tertiary well and produces oscillations at large separations. In
      addition, the stability of a solution of charged polystyrene particles in the
      presence of SPSS was measured using optical light scattering. Because of the
      electrostatic repulsion between the particles, the solution was stable against
      primary flocculation with no added polymer. However, because of long range
      attractive depletion forces, reversible secondary flocculation occurred into a
      local potential energy minimum at low SPSS concentrations (order 0.2 wt%). The
      polymer caused flocculation at a critical flocculation concentration (v *) which
      was found to decrease with increasing particle size. No restabilization of the
      latex dispersions was observed.

PMID- 9241225
TI  - Interpretation of Competitive Adsorption Isotherms in Terms of Affinity
      Distributions
AB  - In the present study we evaluate affinity distributions for competitive
      adsorption isotherms which involve several components. In such a multicomponent
      situation, the affinity distribution becomes a function of several affinity
      constants, and already in the case of two components, little is known about their
      features. In the two-component situation, we have calculated the affinity
      distributions from the adsorption isotherms with a numerical inversion technique.
      This technique is based on a constrained least-squares algorithm and uses a
      regularization function which biases the resulting affinity distribution toward a
      smooth function. The applicability of the procedure was tested with a newly
      derived isotherm, which is based on a fully uncorrelated affinity distribution,
      and with the generalized Langmuir-Freundlich (LF) isotherm, which is known to
      have a perfectly correlated distribution. The present study demonstrates that the
      extended Henderson-Hasselbalch (HH) isotherm has an underlying affinity
      distribution, which displays a partial correlation, while the non-ideal
      competitive adsorption (NICA) isotherm has an affinity distribution with a
      varying degree of correlation. In the competitive situation, the affinity
      distribution thus provides an interesting means to characterize the corresponding
      isotherms. As an illustration of the present techniques, experimental data of
      metal ion binding for a humic acid are analyzed in the same context.

PMID- 9241226
TI  - Phase Behavior of Binary Mixture of Heptaethylene Glycol Decyl Ether and Water:
      Formation of Phase Compound in Solid Phase
AB  - Differential scanning calorimetry (DSC) and Fourier transform infrared
      spectroscopy (FT-IR) were used to construct and characterize the phase diagram
      for a binary mixture of heptaethylene glycol decyl ether (C10 E7 ) and water in
      the temperature range from -60 to 80&deg;C. Plots of the endothermic peak
      temperatures obtained by DSC measurements against compositions provided eutectic
      solid-liquid phase boundaries with a eutectic composition of 34 wt% of H2 O. On
      the other hand, heat of fusion per unit weight of the mixture changed discretely
      at the composition corresponding to the "eutectic" composition. Furthermore, the
      IR spectra obtained for the mixture in the solid phase were well reproduced as a
      superposition of those for the mixture of 34 wt% H2 O and pure components but
      were not reproduced by superimposing the spectra obtained for the solid
      surfactant and ice. These observations indicate that a solid phase compound is
      formed between C10 E7 and water with a stoichiometry of 1:14 and that the
      compound and pure components exist as separate phases, rather than the phases
      separating into surfactant and ice, which would be expected if the C10 E7 /water
      mixture formed a true eutectic mixture system. It is estimated from the
      composition corresponding to the phase compounds that two molecules of water per
      oxyethylene unit are bound to hydrophilic polyoxyethylene chain of C10 E7 to form
      a hydrated compound.

PMID- 9241227
TI  - The Effect of Evaporation on Wilhelmy-Type Measurements of Wetting Tension: Is
      Wetting Equilibrium Reached for Cationic Surfactant Adsorption on Mica?
AB  - The effect of lowering of the liquid level by evaporation on the measured values
      of the advancing wetting tension is calculated and is shown to be able to account
      for most of the change with time of the advancing wetting tension in an earlier
      paper (L. G. T. Eriksson et al., J. Colloid Interface Sci. 181, 476 (1996))
      concerned with the adsorption of hexadecyltrimethylammonium bromide (CTAB) on
      mica, using rates of evaporation ( approximately 0.07 mm/h) measured for that
      setup. With stricter evaporation control, the wetting tension hysteresis is still
      large after 15 h of equilibration, and it is not possible, on that time scale, to
      record the approach to equilibrium of the advancing contact angle for the system
      CTAB/mica.

PMID- 9241228
TI  - Hydrated Electrons in a Quaternary Microemulsion System: A Pulse Radiolysis Study
AB  - Using the technique of pulse radiolysis, hydrated electrons have been produced
      and studied in quaternary microemulsion (sodium lauryl sulfate
      (NaLS)/water/cyclohexane/1-pentanol) system. Remarkably high lifetimes (
      approximately 20 &mgr;s) for hydrated electrons have been obtained. In general,
      these are two orders of magnitude higher than those reported earlier in reverse
      micelles. The water droplet sizes and location of the probes have been determined
      from the decay kinetics of hydrated electrons. The yields and half-lives (t 1/2 )
      of the hydrated electrons vary smoothly as the water droplet sizes are changed.
      We believe that these studies will be useful not only in interpreting electron
      transfer reactions occurring in small water pockets in biological systems but
      also in the production of metal nanoclusters by radiation chemical method.

PMID- 9241230
TI  - Restriction endonuclease isoschizomers ItaI, BsoFI and Fsp4HI are characterised
      by differences in their sensitivities to CpG methylation.
AB  - BsoFI , ItaI and Fsp4HI are isoshizomers of Fnu4HI (5'-GC NGC-3'). Both Fnu4HI
      and BsoFI have previously been shown to be inhibited by cytosine-specific
      methylation within the recognition sequence. Fnu4HI is inhibited if either the
      internal cytosine at position 2 or the external cytosine at position 5 of the
      restriction sequence is methylated, but the precise nature of the methylation
      sensitivity of BsoFI is unclear from the literature. The methylation
      sensitivities of ItaI and Fsp4HI have not previously been reported. By
      methylating the plasmid pUC18 with M.SssI (a DNA cytosine-5'-methyltransferase
      with a specificity for CpG), we have determined that ItaI is sensitive only to
      methylation of internal CpG sites within the restriction sequence. The
      methylation sensitivity of Fsp4HI is identical to that of Fnu4HI, being inhibited
      by methylation of either internal CpG sites or overlapping CpG sites. BsoFI ,
      like the other isoschizomers tested, is sensitive to a combination of internal
      and overlapping CpG methylation. BsoFI is also sensitive to overlapping CpG
      methylation (in the absence of internal CpG methylation) if CpG overlap with both
      sides of the recognition sequence. Sites containing one overlapping CpG (in the
      absence of internal CpG) are cut when methylated but show marked individual
      variation in their rates of cleavage. Considerable variation in the rate of
      cleavage by BsoFI is also observed at sites containing only internal methylated
      CpG. Some sites are cut slowly, whilst others fail to cut even after prolonged
      incubation with excess of enzyme.

PMID- 9241231
TI  - Co-packaging of non-vector RNAs generates replication-defective retroviral vector
      particles: a novel approach for blocking retrovirus replication.
AB  - A Moloney murine leukemia virus (MoMuLV)-derived packaging retroviral vector,
      pUCMoTN-PR3, was previously developed in which the packaging (psi) signal was
      cloned within the 5'-long terminal repeat (LTR) U3-r and U5 sequences. The MoTN
      PR3 vector particles released from a transfected packaging cell line contain RNAs
      with r-psi-U5 sequences at the 5'-end and U3-r sequences at the 3'-end. Upon
      infection, these vector particles can efficiently transduce the neomycin
      phosphotransferase (neo) gene to the target cells. The structure of the proviral
      DNA synthesized in these cells was shown to contain modified 5'- and 3'-LTRs with
      U3-r-psi-U5 sequences, indicating that this vector can undergo reverse
      transcription and integration. Analysis of psi signal-containing RNAs revealed
      that in addition to vector RNA transcribed from the MoMuLV 5'-LTR promoter,
      readthrough neo RNA transcribed from the internal herpes simplex virus (HSV)
      thymidine kinase (tk) promoter and cellular RNAs transcribed from the MoMuLV 3'
      LTR promoter are produced. Of these, the downstream cellular RNAs are also
      packaged within the vector particles. These vector particles containing the
      vector and non-vector RNAs carrying the MoMuLV psi signal are non-infectious. It
      is proposed that intracellular expression of packageable non-viral RNAs may
      represent an effective strategy for inhibiting animal and plant virus
      replication.

PMID- 9241229
TI  - Comparative sequence analysis of ribonucleases HII, III, II PH and D.
AB  - Escherichia coli ribonucleases (RNases) HII, III, II, PH and D have been used to
      characterise new and known viral, bacterial, archaeal and eucaryotic sequences
      similar to these endo- (HII and III) and exoribonucleases (II, PH and D).
      Statistical models, hidden Markov models (HMMs), were created for the RNase HII,
      III, II and PH and D families as well as a double-stranded RNA binding domain
      present in RNase III. Results suggest that the RNase D family, which includes
      Werner syndrome protein and the 100 kDa antigenic component of the human
      polymyositis scleroderma (PMSCL) autoantigen, is a 3'-->5' exoribonuclease
      structurally and functionally related to the 3'-->5' exodeoxyribonuclease domain
      of DNA polymerases. Polynucleotide phosphorylases and the RNase PH family, which
      includes the 75 kDa PMSCL autoantigen, possess a common domain suggesting similar
      structures and mechanisms of action for these 3'-->5' phosphorolytic enzymes.
      Examination of HMM-generated multiple sequences alignments for each family
      suggest amino acids that may be important for their structure, substrate binding
      and/or catalysis.

PMID- 9241232
TI  - The Ogg1 protein of Saccharomyces cerevisiae: a 7,8-dihydro-8-oxoguanine DNA
      glycosylase/AP lyase whose lysine 241 is a critical residue for catalytic
      activity.
AB  - The OGG1 gene of Saccharomyces cerevisiae codes for a DNA glycosylase that
      excises 7,8-dihydro-8- oxoguanine (8-OxoG) and 2,6-diamino-4-hydroxy-5- N 
      methylformamidopyrimidine (Fapy) from damaged DNA. In this paper, we have
      analysed the substrate specificity and the catalytic mechanism of the Ogg1
      protein acting on DNA subtrates containing 8-OxoG residues or
      apurinic/apyrimidinic (AP) sites. The Ogg1 protein displays a marked preference
      for DNA duplexes containing 8-OxoG placed opposite a cytosine, the rank order for
      excision of 8-OxoG and cleavage efficiencies being 8-OxoG/C >8-OxoG/T >>8-OxoG/G
      and 8-OxoG/A. The cleavage of the DNA strand implies the excision of 8-OxoG
      followed by abeta-elimination reaction at the 3'-side of the resulting AP site.
      The Ogg1 protein efficiently cleaves a DNA duplex where a preformed AP site is
      placed opposite a cytosine (AP/C). In contrast, AP/T, AP/A or AP/G substrates are
      incised with a very low efficiency. Furthermore, cleavage of 8-OxoG/C or AP/C
      substrates implies the formation of a reaction intermediate that is converted
      into a stable covalent adduct in the presence of sodium borohydre (NaBH4).
      Therefore, the Ogg1 protein is a eukaryotic DNA glycosylase/AP lyase. Sequence
      homology searches reveal that Ogg1 probably shares a common ancestor gene with
      the endonuclease III of Escherichia coli. A consensus sequence indicates a highly
      conserved lysine residue, K120 of endonuclease III or K241 of Ogg1, respectively.
      Mutations of K241 to Gln (K241Q) and Arg (K241R) have been obtained after site
      directed mutagenesis of OGG1. Mutation K241Q completely abolishes DNA glycosylase
      activity and covalent complex formation in the presence of NaBH4. However, the
      K241Q mutant still binds DNA duplexes containing 8-OxoG/C. In contrast, K241R
      mutation results in a catalytically active form of Ogg1. These results strongly
      suggest that the free amino group of Lys241 is involved in the catalytic
      mechanism of the Ogg1 protein.

PMID- 9241233
TI  - Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse
      transcriptase.
AB  - Human immunodeficiency virus type 1 (HIV-1) variants with resistance mutations in
      the reverse transcriptase (RT) gene appear during drug therapy with the
      nucleoside analogue 2',3'-dideoxy-3'-thiacytidine (3TC). These 3TC-resistant RT
      variants have a single point mutation that changes the 184Met residue into either
      Val or Ile. Both codon 184 variants are frequently observed in 3TC-treated
      patients and can also be selected in cell culture infections. We demonstrated
      previously that the 184Ile and 184Val RT enzymes exhibit a processivity defect in
      in vitro assays, with 184Ile being the least processive enzyme [Met(wt) >Val
      >Ile]. In this study, we measured the polymerase fidelity of the wild-type
      (184Met) and 3TC-resistant RT enzymes (184Ile and 184Val) on DNA and RNA
      templates. Both virion- extracted and Escherichia coli -expressed recombinant RT
      enzymes were used to measure the nucleotide misinsertion and mispair extension
      efficiencies. The 3TC-resistant enzymes were more accurate than the wild-type RT
      protein in both type of assays. The order of accuracy observed for the codon 184
      variants [Ile >Val >Met(wt)] may suggest an inverse correlation between the
      fidelity and processivity properties of these enzymes.

PMID- 9241234
TI  - A two unit antisense RNA cassette test system for silencing of target genes.
AB  - This communication describes a two unit antisense RNA cassette system for use in
      gene silencing. Cassettes consist of a recognition unit and an inhibitory unit
      which are transcribed into a single RNA that carries sequences of non-contiguous
      complementarity to the chosen target RNA. The recognition unit is designed as a
      stem-loop for rapid formation of long- lived binding intermediates with target
      sequences and resembles the major stem-loop of a naturally occurring antisense
      RNA, CopA. The inhibitory unit consists of either a sequence complementary to a
      ribosome binding site or of a hairpin ribozyme targeted at a site within the
      chosen mRNA. The contributions of the individual units to inhibition was assessed
      using the lacI gene as a target. All possible combinations of recognition and
      inhibitory units were tested in either orientation. In general, inhibition of
      lacI expression was relatively low. Fifty per cent inhibition was obtained with
      the most effective of the constructs, carrying the recognition stem-loop in the
      antisense orientation and the inhibitory unit with an anti-RBS sequence. Several
      experiments were performed to assess activities of the RNAs in vitro and in vivo
      : antisense RNA binding assays, cleavage assays, secondary structure analysis as
      well as Northern blotting and primer extension analysis of antisense and target
      RNAs. The problems associated with this antisense RNA approach as well as its
      potential are discussed with respect to possible optimization strategies.

PMID- 9241235
TI  - Recent evolutionary acquisition of alternative pre-mRNA splicing and 3'
      processing regulations induced by intronic B2 SINE insertion.
AB  - Contrary to the membrane-anchored leukemia inhibitory factor receptor (LIFR), the
      mouse soluble LIFR is an inhibitor of LIF action, possibly through a ligand
      titration effect. Two mRNA species encoding the soluble LIFR have been
      identified. Since the 3'-untranslated end of the shorter form was shown to
      contain a B2 element, we have examined the possibility that this SINE may be
      responsible for LIFR mRNA truncation. Transient expression assays, using B2
      derived or intron-derived sequences independently or in conjunction, show that
      the B2 element has fortuitously unmasked a cryptic pre-mRNA 3'processing activity
      of silent intron sequences. The corresponding locus of the rat genome has been
      isolated and was shown to be devoid of any retroposon, which may explain why no
      soluble LIFR has yet been identified in any other species and further indicates
      that the B2 insertion event in the mouse LIFR gene has occurred recently during
      evolution. And yet, a tight tissue-specific regulation of alternative synthesis
      of soluble and membrane-bound LIFR mRNA has already emerged in mice. These
      results provide striking evidence for the rapid influence of retroposition on
      genome expression.

PMID- 9241236
TI  - The elimination of primer-dimer accumulation in PCR.
AB  - We attempted to produce primer-dimers (PDs) from a variety of primers with
      differing types and extents of complementarity. Where PDs were produced they were
      cloned and sequenced. We were unable to produce detectable PDs either with
      individual primers alone or with similar sequence primers even if they had
      3'complementarity. These observations led to the hypothesis that a system could
      be developed whereby the accumulation of PDs in a PCR may be eliminated. We
      demonstrate a method for the general suppression of PD formation that uses a
      sequence of additional nucleotides (a Tail) at the 5' ends of amplimers. Tailed
      amplimers are present at low concentration and only participate during early
      cycles of PCR. In subsequent PCR cycles, amplification is achieved using a single
      primer that has the same sequence as that of the Tail portion of the early cycle
      primers, here we refer to this as a Tag. When products are small, as with PDs,
      there is a high local concentration of complementary sequences derived from the
      Tail. This favours the annealing of the complementary ends of a single strand
      produced by tailed primer interactions and gives rise to 'pan-handle' structures.
      The formation of these outcompetes the annealing of further Tag primers thereby
      preventing the accumulation of non-specific PD products. This aids the design of
      large multiplex reactions and provides a means of detecting specific amplicons
      directly in the reaction vessel by using an intercalating dye.

PMID- 9241237
TI  - Enhancement of the nucleosomal pattern in sequences of lower complexity.
AB  - Intuitively, the complexity of a given DNA sequence is related to the number of
      various superimposed biological messages it contains. Here we assess the
      expectation that in nucleosome DNA sequences of lower linguistic complexity, the
      nucleosome DNA positioning pattern would be more pronounced than in those of
      higher linguistic complexity. The nucleosome DNA positioning pattern is one of
      the weakest (highly degenerate) sequence patterns. It has been extracted recently
      by specially designed multiple alignment procedures. We applied the most
      sensitive of these procedures to nearly equal subsets of a nucleosome database
      separated according to linguistic complexity. The pattern extracted from the
      subset of the simpler nucleosome sequences not only possesses all major
      attributes of the known nucleosomal pattern, but is substantially stronger with
      respect to amplitude in comparison with the total database. This result
      constitutes the first demonstration that a weak pattern can be significantly
      enhanced by selective treatment of a lower complexity subset of the sequence
      ensemble under consideration.

PMID- 9241238
TI  - Protein-DNA interactions in the human beta-globin locus control region
      hypersensitive site-2 as revealed by four nitrogen mustards.
AB  - Four nitrogen mustards have been used in this study to examine protein-DNA
      interactions in intact human cells, specifically at the locus control region
      hypersensitive site-2 (LCR HS-2) of the human beta-globin locus. Three of these
      nitrogen mustards are DNA-targeted by attachment of an acridine or amsacrine
      intercalating chromophore, while the fourth (chlorambucil) is a non-targeted
      mustard. The ligation-mediated PCR technique was used to determine the sites of
      damage at base pair resolution on DNA sequencing gels. A densitometric comparison
      was made between DNA damaged in intact erythroid K562 cells and in purified DNA.
      The intensity of DNA damage sites in the LCR HS-2 were found to differ
      significantly between intact K562 cells and purified DNA. At the NF-E2/AP-1
      motif, pronounced damage protection was observed in DNA derived from drug treated
      cells. The nuclear factor- erythroid 2 (NF-E2) protein factor is thought to bind
      at this NF-E2/AP-1 motif in K562 cells. Other sites of protection and enhancement
      that corresponded to known transcription factor binding sites were also detected.
      These nitrogen mustards are therefore very effective compounds for detection of
      transcription factor binding to DNA in intact cells and are superior to other
      commonly used agents. The sequence selectivity of the compounds was determined
      using plasmid DNA and compared to that found in intact cells. The acridine-based
      nitrogen mustard had a preference for forming adducts at guanine bases, while the
      two amsacrine-based nitrogen mustards and chlorambucil formed adducts at both
      guanine and adenine bases.

PMID- 9241239
TI  - Cell-specific in vivo DNA-protein interactions at the proximal promoters of the
      pro alpha 1(I) and the pro alpha2(I) collagen genes.
AB  - We performed in vivo dimethylsulfate footprinting of the 220 bp mouse proximal
      proalpha1(I) collagen promoter and the 350 bp mouse proximal proalpha2(I)
      collagen promoter in BALB/3T3 fibroblasts, primary mouse skin fibroblasts, S-194
      B cells, NMuLi liver epithelial cells and RAG renal adenocarcinoma cells and in
      vitro DNase I footprinting of these promoters using nuclear extracts of these
      different cell types. Whereas proalpha1(I) and proalpha2(I) collagen RNAs were
      present in BALB/3T3 fibroblasts and primary fibroblasts, these RNAs could not be
      detected in the three other cell lines. Comparison of in vitro DNase I footprints
      for each of the two proximal collagen promoters indicated that the patterns of
      protection were very similar with the different nuclear extracts, suggesting that
      the DNA binding proteins binding to these promoters were present in all cell
      types tested. In contrast, in vivo footprints over these proximal promoters were
      cell-specific, occurring only in fibroblast cells and not in the other three cell
      types. The in vivo footprints were generally located within the in vitro
      footprinted regions. Our results suggest that although all cell types tested
      contained nuclear proteins that can bind to the proximal proalpha1(I) and
      proalpha2(I) collagen promoters in vitro , it is only in fibroblasts that these
      proteins bind to their cognate sites in vivo . We discuss possible regulatory
      mechanisms in type I collagen genes that can contribute to the cell-specific in
      vivo protein-DNA interactions at the proximal promoters.

PMID- 9241240
TI  - Kinetic studies on the formation of intermolecular triple helices.
AB  - We have used DNase I footprinting to examine the association kinetics of GA-, GT-
      and CT-containing oligonucleotides with the target sequence (GGA)5GG. (CCT)5CC.
      These reactions are slow yielding bimolecular association rate constants between
      50 and 2000 M-1s-1. We find that GT-containing oligonucleotides bind much faster
      than GA- or CT-containing third strands. In each case the observed rate constants
      are faster at the centre than at the edges of the target site. Although several
      explanations can be offered for this observation, it is consistent with a model
      in which triplex formation at this repetitive site is achieved via intermediate
      complexes in which the third strand is not properly aligned with its target and
      which subsequently migrate to the correct position.

PMID- 9241241
TI  - The Cryphonectria parasitica plasmid pUG1 contains a large ORF with motifs
      characteristic of family B DNA polymerases.
AB  - The isolation and characterization of the circular mitochondrial plasmid pUG1
      from the ascomycete Cryphonectria parasitica is described. The entire sequence
      (4182 bp) was obtained and high similarities to DNA-dependent DNA polymerases
      were revealed. Strikingly common features with the DNA polymerases encoded by the
      Neurospora intermedia plasmids Fiji and LaBelle, such as matches to the conserved
      motifs A and B and the presence of TTD instead of DTD in motif C, were found,
      suggesting the existence of a distinct group of members of the B DNA family
      polymerases. These strong similarities between the plasmids might suggest a
      common origin of the C.parasitica and the Neurospora plasmids.

PMID- 9241242
TI  - Cell cycle regulation of RPA1 transcript levels in the trypanosomatid Crithidia
      fasciculata.
AB  - Transcripts of both mitochondrial and nuclear DNA replication genes accumulate
      periodically during the cell cycle in Crithidia fasciculata. An octameric
      consensus sequence with a conserved hexameric core was found previously to be
      required for cycling of the TOP2 transcript, encoding the mitochondrial DNA
      topoisomerase. We show here that the rate of synthesis of the p51 protein, the
      large subunit of nuclear replication protein-A encoded by the RPA1 gene, varies
      during the cell cycle in parallel with RPA1 mRNA level. Plasmids expressing a
      truncated form of RPA1 (Delta RPA1 ) were used to identify cis elements required
      for cycling of the Delta RPA1 transcript. Sequences within the RPA1 5'
      untranslated region (UTR) were found to be necessary for cycling of the Delta
      RPA1 transcript. These sequences also function when transposed 3'of the Delta
      RPA1 coding sequence. A 121 bp fragment of this sequence can confer cycling on a
      heterologous transcript, but is inactivated when two consensus octamers within
      the sequence are mutated. Mutation of these two octamers in the full-length 5'
      UTR ofDelta RPA1 is insufficient to abolish cycling of the mRNA unless three
      additional octamers having single base changes within the hexameric core are also
      mutated. Thus, common octameric sequence elements are involved in periodic
      accumulation of both the TOP2 and RPA1 transcripts.

PMID- 9241243
TI  - In vivo fate of phosphorothioate antisense oligodeoxynucleotides: predominant
      uptake by scavenger receptors on endothelial liver cells.
AB  - Systemically administered phosphorothioate antisense oligodeoxynucleotides can
      specifically affect the expression of their target genes, which affords an
      exciting new strategy for therapeutic intervention. Earlier studies point to a
      major role of the liver in the disposition of these oligonucleotides. The aim of
      the present study was to identify the cell type(s) responsible for the liver
      uptake of phosphorothioate oligodeoxynucleotides and to examine the mechanisms
      involved. In our study we used ISIS-3082, a phosphorothioate antisense
      oligodeoxynucleotide specific for murine ICAM-1. Intravenously injected [3H]ISIS
      3082 (dose: 1 mg/kg) was cleared from the circulation of rats with a half-life of
      23.3+/-3.8 min. At 90 min after injection (>90% of [3H]ISIS-3082 cleared), the
      liver contained the most radioactivity, whereas the second-highest amount was
      recovered in the kidneys (40.5+/-1.4% and 17.9+/-1.3% of the dose, respectively).
      Of the remaining tissues, only spleen and bone marrow actively accumulated
      [3H]ISIS-3082. By injecting different doses of [3H]ISIS-3082, it was found that
      uptake by liver, spleen, bone marrow, and kidneys is saturable, which points to a
      receptor-mediated process. Subcellular fractionation of the liver indicates that
      ISIS-3082 is internalized and delivered to the lysosomes. Liver uptake occurs
      mainly (for 56.1+/-3.0%) by endothelial cells, whereas parenchymal and Kupffer
      cells account for 39.6+/-4.5 and 4.3+/-1.7% of the total liver uptake,
      respectively. Preinjection of polyinosinic acid substantially reduced uptake by
      liver and bone marrow, whereas polyadenylic acid was ineffective, which indicates
      that in these tissues scavenger receptors are involved in uptake. Polyadenylic
      acid, but not polyinosinic acid, reduced uptake by kidneys, which suggests renal
      uptake by scavenger receptors different from those in the liver. We conclude that
      scavenger receptors on rat liver endothelial cells play a predominant role in the
      plasma clearance of ISIS-3082. As scavenger receptors are also expressed on human
      endothelial liver cells, our findings are probably highly relevant for the
      therapeutic application of phosphorothioate oligodeoxynucleotides in humans. If
      the target gene is not localized in endothelial liver cells, the therapeutic
      effectiveness might be improved by developing delivery strategies that redirect
      the oligonucleotides to the actual target cells.

PMID- 9241245
TI  - DNA duplexes with reactive dialdehyde groups as novel reagents for cross-linking
      to restriction- modification enzymes.
AB  - To create new, effective reagents for affinity modification of restriction
      modification (R-M) enzymes, a regioselective method for reactive dialdehyde group
      incorporation into oligonucleotides, based on insertion of a 1-beta-D
      galactopyranosylthymine residue, has been developed. We synthesized DNA duplex
      analogs of the substrates of the Eco RII and Mva I R-M enzymes that contained a
      galactose or periodate-oxidized galactose residue as single substituents either
      in the center of the Eco RII (Mva I) recognition site or in the flanking
      nucleotide sequence. The dependence of binding, cleavage and methylation of these
      substrate analogs on the modified sugar location in the duplex was determined.
      Cross-linking of the reagents to the enzymes under different conditions was
      examined. M. Eco RII covalent attachment to periodate-oxidized substrate analogs
      proceeded in a specific way and to a large extent depended on the location of the
      reactive dialdehyde group in the substrate. The yield of covalent attachment to a
      DNA duplex with a dialdehyde group in the flanking sequence with Eco RII or Mva I
      methylases was 9-20% and did not exceed 4% for R. Eco RII.

PMID- 9241244
TI  - A new method to monitor the rate of conformational transitions in RNA.
AB  - Many RNAs need Mg2+to produce stable tertiary structures. Here we describe a
      simple method to measure the rate and activation parameters of tertiary structure
      unfolding that exploits this Mg2+dependence. Our approach is based on mixing an
      RNA solution with excess EDTA in a stopped-flow instrument equipped with an
      absorbance detector, under conditions of temperature and ionic strength where,
      after chelation of Mg2+, tertiary structure unfolds. We have demonstrated the
      utility of this method by studying phenylalanine-specific transfer RNA from yeast
      (tRNAPhe) because the unfolding rates and the corresponding activation parameters
      have been determined previously and provide a benchmark for our technique. We
      find that within error, our stopped-flow method reproduces both the rate and
      activation enthalpy for tertiary unfolding of yeast tRNAPhe measured previously
      by temperature-jump relaxation kinetics. Since many different RNAs require
      divalent magnesium for tertiary structure stabilization, this technique should be
      applicable to study the folding of other RNAs.

PMID- 9241246
TI  - 2',5'-linked oligo-3'-deoxyribonucleoside phosphorothioate chimeras: thermal
      stability and antisense inhibition of gene expression.
AB  - 2',5'-Linked oligo-3'-deoxyribonucleotides bind selectively to complementary RNA
      but not to DNA. These oligonucleotides (ODNs) do not recognize double-stranded
      DNA by Hoogsteen triplex formation and the complexes formed by these ODNs with
      RNA are not substrates for Escherichia coli RNase H. Substitution of the 2',5'
      phosphodiester backbone by phosphorothioate linkages gives 2',5'-linked oligo-3'
      deoxynucleoside phosphorothioate ODNs that exhibit significantly less non
      specific binding to cellular proteins or thrombin. Incorporation of a stretch of
      seven contiguous 3',5'-linked oligo-2'-deoxynucleoside phosphorothioate linkages
      in the center of 2',5'-linked ODNs (as a putative RNase H recognition site)
      afford chimeric antisense ODNs that retain the ability to inhibit steroid 5alpha
      reductase (5alphaR) expression in cell culture.

PMID- 9241247
TI  - Androgen receptor-associated protein complex binds upstream of the androgen
      responsive elements in the promoters of human prostate-specific antigen and
      kallikrein 2 genes.
AB  - An increasing number of proteins which bind to hormone-dependent nuclear
      receptors and mediate their effects on gene expression are being identified. The
      human prostate-specific antigen (PSA) and kallikrein 2 (KLK2) genes are regulated
      by the androgen receptor (AR). Using electrophoresis mobility shift assays
      (EMSA), a common nuclear protein(s) which binds upstream of the androgen
      responsive elements (AREs) in the PSA and KLK2 promoters was identified. Binding
      occurred between bp -539 and -399 and bp -349 and -224 in the PSA and KLK2
      promoters respectively, which were shown previously to be necessary for AR
      mediated transactivation. Glutathione S-transferase (GST)-AR fusion proteins were
      constructed to determine whether the AR interacted directly with this protein or
      protein complex. Specific interactions were observed with AR fusion proteins
      containing the DNA binding domain. EMSA supershift experiments and GST-AR pull
      down experiments followed by Western blotting identified a Fos-related protein(s)
      of approximately 40 kDa as part of this complex. Competition experiments with a
      double-stranded oligonucleotide containing an AP-1 binding site demonstrated that
      DNA binding was not mediated by AP-1. These results indicate that a Fos
      containing protein complex distinct from AP-1 binds upstream of the AREs in the
      PSA and KLK2 promoters, interacts with the AR and may participate in regulation
      of these two androgen-responsive genes.

PMID- 9241248
TI  - Brief expression of a GFP cre fusion gene in embryonic stem cells allows rapid
      retrieval of site-specific genomic deletions.
AB  - The Cre DNA recombinase of bacteriophage P1 has become a useful tool for precise
      genomic manipulation in embryonic stem (ES) cells that have been gene modified by
      homologous recombination. We have re-engineered the cre gene to allow ready
      identification of living Cre+cells by constructing a functional fusion between
      Cre and an enhanced green fluorescent protein from Aequorea victoria (GFPS65T).
      The GFP cre fusion gene product rapidly targeted the nucleus in the absence of
      any exogenous nuclear localization signal. Moreover, GFPCre catalyzed efficient
      DNA recombination in both a mouse 3T3 derivative cell line and in murine ES
      cells. Fluorescence- activated cell sorting (FACS) of transiently GFP cre 
      transfected ES cells not only allowed rapid and efficient isolation of Cre+cells
      after DNA transfection but also demonstrated that a burst of Cre expression is
      sufficient to commit cells to Cre-mediated 'pop-out' of loxP -tagged DNA from the
      genome. Thus, GFP cre allows rapid identification of living cells in which loxP -
      flanked DNA sequences are destined to be removed from the genome by Cre-mediated
      recombination without reliance on recombinational activation or inactivation of a
      marker gene at the target locus. In addition, the GFP cre fusion gene will prove
      useful in tracing tissue-specific Cre expression in transgenic animals, thereby
      facilitating the generation and analysis of conditional gene knockout mice.

PMID- 9241249
TI  - Functional analysis of point mutations in human flap endonuclease-1 active site.
AB  - Human flap endonuclease-1 (hFEN-1) is highly homologous to human XPG,
      Saccharomyces cerevisiae RAD2 and S.cerevisiae RTH1 and shares structural and
      functional similarity with viral exonucleases such as T4 RNase H, T5 exonuclease
      and prokaryotic DNA polymerase 5'nucleases. Sequence alignment of 18 structure
      specific nucleases revealed two conserved nuclease domains with seven conserved
      carboxyl residues and one positively charged residue. In a previous report, we
      showed that removal of the side chain of each individual acidic residue results
      in complete loss of flap endonuclease activity. Here we report a detailed
      analysis of substrate cleavage and binding of these mutant enzymes as well as of
      an additional site-directed mutation of a conserved acidic residue (E160). We
      found that the active mutant (R103A) has substrate binding and cleavage activity
      indistinguishable from the wild type enzyme. Of the inactive mutants, one (D181A)
      has substrate binding properties comparable to the wild type, while three others
      (D34A, D86A and E160A) bind with lower apparent affinity (2-, 9- and 18-fold
      reduced, respectively). The other mutants (D158A, D179A and D233A) have no
      detectable binding activity. We interpret the structural implications of these
      findings using the crystal structures of related enzymes with the flap
      endonuclease activity and propose that there are two metal ions (Mg2+or Mn2+) in
      hFEN enzyme. These two metal coordinated active sites are distinguishable but
      interrelated. One metal site is directly involved in nucleophile attack to the
      substrate phosphodiester bonds while the other may stabilize the structure for
      the DNA substrate binding. These two sites may be relatively close since some of
      carboxyl residues can serve as ligands for both sites.

PMID- 9241250
TI  - Identification of preferred hTBP DNA binding sites by the combinatorial method
      REPSA.
AB  - Here we describe the application of a novel combinatorial method, restriction
      endonuclease protection selection and amplification (REPSA), to identification of
      a consensus DNA binding site for the TATA binding subunit (hTBP) of the human
      general transcription factor TFIID. Unlike most combinatorial methods, REPSA is
      based on inhibition of an enzymatic template inactivation process by specific
      ligand-DNA complexes. The mild conditions of this method allow examination of
      proteins with atypical binding characteristics (e.g. limited discrimination
      between specific and non-specific binding sites), such as those found with hTBP.
      Analysis of 57 emergent sequences identified 47 sequences containing consensus 6
      bp TATA elements as previously defined. However, further examination of these
      sequences indicated that a larger consensus, 5'-TATAAATA-3', could be supported
      by the data. Studies of the binding affinities and transcriptional activities of
      these four consensus TATA sequences demonstrated that hTBP binding affinity
      correlated directly with transcriptional activity in vitro and that the TATAAATA
      sequence was the best among the TATA sequences investigated.

PMID- 9241251
TI  - Multiple isoforms of GAGA factor, a critical component of chromatin structure.
AB  - The GAGA transcription factor of Drosophila melanogaster is ubiquitous and plays
      multiple roles. Characterization of cDNA clones and detection by domain- specific
      antibodies has revealed that the 70-90 kDa major GAGA species are encoded by two
      open reading frames producing GAGA factor proteins of 519 amino acids (GAGA-519)
      and 581 amino acids (GAGA-581), which share a common N-terminal region that is
      linked to two different glutamine-rich C-termini. Purified recombinant GAGA-519
      and GAGA-581 proteins can form homomeric complexes that bind specifically to a
      single GAGA sequence in vitro. The two GAGA isoforms also function similarly in
      transient transactivation assays in tissue culture cells and in chromatin
      remodeling experiments in vitro . Only GAGA-519 protein accumulates during the
      first 6 h of embryogenesis. Thereafter, both GAGA proteins are present in nearly
      equal amounts throughout development; in larval salivary gland nuclei they
      colocalize completely to specific regions along the euchromatic arms of the
      polytene chromosomes. Coimmunoprecipitation of GAGA-519 and GAGA-581 from crude
      nuclear extracts and from mixtures of purified recombinant proteins, indicates
      direct interactions. We suggest that homomeric complexes of GAGA-519 may function
      during early embryogenesis; both homomeric and heteromeric complexes of GAGA-519
      and GAGA-581 may function later.

PMID- 9241252
TI  - Structure of the hydrogen bonding complex of O6-methylguanine with cytosine and
      thymine during DNA replication.
AB  - During DNA replication, mutations occur when an incorrect dNTP is incorporated
      opposite a carcinogen-modified nucleotide. We have probed the structures of the
      interaction between O 6-methylguanine ( O 6mG) and cytosine and thymine during
      replication by kinetic means in order to examine the structure during the rate
      determining step. The kinetics of incorporation of dCTP and dTTP opposite O 6mG
      and three analogs, S 6-methyl-6-thioguanine, O 6-methyl-1-deazaguanine and O 6
      methylhypoxanthine, have been measured with four polymerases, the Klenow fragment
      of DNA polymerase I, the Klenow fragment with the proof-reading exonuclease
      inactivated, Taq and Tth polymerases. In the insertion of dTTP opposite O 6mG, a
      large decrease in V max/ K m was observed only upon modification of the N1
      position. This result is consistent with a Watson-Crick type configuration. For
      the incorporation of dCTP, the V max/ K m was significantly decreased only with
      removal of the exocyclic amino group at the 2 position. The pH dependence of the
      ratio of incorporation of dCTP and dTTP was independent of pH at physiological
      pH. This result suggests that dCTP is incorporated via an uncharged complex such
      as the wobble configuration.

PMID- 9241254
TI  - Rapid and efficient site-directed mutagenesis by single-tube 'megaprimer' PCR
      method.
AB  - We describe a rapid and efficient megaprimer PCR procedure for site-directed
      mutagenesis that does not require any intermediate purification of DNA between
      the two rounds of PCR. This protocol is based on the design of forward and
      reverse flanking primers with significantly different melting temperatures ( T
      m). A megaprimer is synthesized in the first PCR reaction using a mutagenic
      primer, the low T m flanking primer and a low annealing temperature. The second
      PCR reaction is performed in the same tube as the first PCR and utilizes the high
      T m flanking primer, the megaprimer product of the first PCR and a high annealing
      temperature, which prevents priming by the low T m primer from the first PCR
      reaction. We have used this protocol with two different plasmids to produce cDNAs
      encoding seven distinct mutated proteins. We have observed an average mutagenesis
      efficiency of 82% in these experiments.

PMID- 9241255
TI  - Improved efficiency sos recruitment system: expression of the mammalian GAP
      reduces isolation of Ras GTPase false positives.
AB  - The Sos recruitment system (SRS) is a novel genetic method for detecting protein
      protein interactions. The method is based on localizing Sos, a Ras guanyl
      nucleotide exchange factor (GEF), to the plasma membrane through interaction
      between two fusion proteins. Mammalian Ras can bypass the requirement for a
      functional Ras GEF and represents a predictable false positive in this system.
      This report demonstrates that introduction of mammalian GTPase activating protein
      (mGAP) reduces the isolation of Ras false positives in SRS screens of mammalian
      cDNA libraries, thereby significantly enhancing the efficiency of the system.

PMID- 9241253
TI  - RNA-protein interactions within the 3 ' untranslated region of vimentin mRNA.
AB  - Several functions have been attributed to protein binding within the
      3'untranslated region (3'UTR) of mRNA, including mRNA localization, stability,
      and translational repression. Vimentin is an intermediate filament protein whose
      3'untranslated sequence is highly conserved between species. In order to identify
      sequences that might play a role in vimentin mRNA function, we synthesized32P
      labeled RNA from different regions of vimentin's 3'UTR and assayed for protein
      binding with HeLa extracts using band shift assays. Sequences required for
      binding are contained within a region 61-114 nucleotides downstream of the stop
      codon, a region which is highly conserved from Xenopus to man. As judged by
      competition assays, binding is specific. Solution probing studies of 32P-labeled
      RNA with various nucleases and lead support a complex stem and loop structure for
      this region. Finally, UV cross-linking of the RNA-protein complex identifies an
      RNA binding protein of 46 kDa. Fractionation of a HeLa extract on a sizing column
      suggests that in addition to the 46 kDa protein, larger complexes containing
      additional protein(s) can be identified. Vimentin mRNA has been shown to be
      localized to the perinuclear region of the cytoplasm, possibly at sites of
      intermediate filament assembly. To date, all sequences required for localization
      of various mRNAs have been confined to the 3'UTR. Therefore, we hypothesize that
      this region and associated protein(s) might be important for vimentin mRNA
      function such as in localization.

PMID- 9241256
TI  - Quantitative DNA slot blot analysis: inhibition of DNA binding to membranes by
      magnesium ions.
AB  - Titers of wild-type and recombinant adeno-associated viruses are routinely
      determined by DNA slot blot analysis. The binding of viral DNA to nylon membranes
      was found to be inhibited by magnesium ions, which are critical components of the
      DNase I digestion carried out prior to slot blot analysis. Mg2+ions also
      interfered with the adsorption of plasmid DNA to nylon and nitrocellulose
      membranes. These observations yield practical insights into the poorly understood
      mechanisms by which DNA molecules are retained on solid supports.

PMID- 9241258
TI  - Cloning questions.

PMID- 9241257
TI  - Potassium permanganate and tetraethylammonium chloride are a safe and effective
      substitute for osmium tetroxide in solid-phase fluorescent chemical cleavage of
      mismatch.
AB  - Whilst chemical cleavage of mismatch (CCM) detects all point mutations in DNA,
      its widespread use has been hampered by the complex multistage methodology and
      the need for toxic chemicals, in particular osmium tetroxide. Here we show that
      osmium tetroxide can be replaced by potassium permanganate, giving the same
      spectrum of mutation detection, but with greater sensitivity. The use of
      potassium permanganate is compatible with solid phase capture and fluorescent
      detection, giving a safer method of mutation detection. We present here a
      comparison of CCM with osmium tetroxide and with potassium permanganate, tested
      on a complete set of single base pair mismatches and a number of small
      insertion/deletions.

PMID- 9241259
TI  - Ironing out anaemia.

PMID- 9241260
TI  - Tumour-suppressor genes: evolving definitions in the genomic age.

PMID- 9241261
TI  - Waiting for frataxin.

PMID- 9241262
TI  - alpha-Synuclein--a link between Parkinson and Alzheimer diseases?

PMID- 9241263
TI  - Silent mutation induces exon skipping of fibrillin-1 gene in Marfan syndrome.

PMID- 9241264
TI  - TSG101 may be the prototype of a class of dominant negative ubiquitin regulators.

PMID- 9241265
TI  - Absence of rearrangements in the tumour susceptibility gene TSG101 in human
      breast cancer.

PMID- 9241266
TI  - Germline mutations in PTEN are present in Bannayan-Zonana syndrome.

PMID- 9241267
TI  - Impaired nuclear localization of defective DNA helicases in Werner's syndrome.

PMID- 9241268
TI  - Deletion of p21 cannot substitute for p53 loss in rescue of mdm2 null lethality.

PMID- 9241269
TI  - Functional genomics in mice by tagged sequence mutagenesis.
AB  - Most mammalian genes will soon be characterized as cDNA sequences with little
      information about their function. To utilize this sequence information for large
      scale functional studies, a gene trap retrovirus shuttle vector has been
      developed to disrupt genes expressed in murine embryonic stem (ES) cells. A
      library of mutant clones was isolated, and regions of genomic DNA adjacent to 400
      independent provirus inserts were cloned and sequenced. The flanking sequences,
      designated 'promoter-proximal sequence tags', or PSTs, identified 63 specific
      genes and anonymous cDNAs disrupted as a result of virus integration. The
      efficiency of tagged sequence mutagenesis suggests that many of the 10,000-20,000
      genes expressed in ES cells can be targeted, providing defined mutations for the
      analysis of gene functions in vivo. In addition, PSTs provide the first expressed
      sequence tags derived from genomic DNA, and define gene features such as exon
      boundaries and promoters that are missing from cDNA sequences.

PMID- 9241270
TI  - Studies of human, mouse and yeast homologues indicate a mitochondrial function
      for frataxin.
AB  - Friedreich's ataxia is due to loss of function mutations in the gene encoding
      frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization
      analyses revealed that mouse frataxin expression correlates well with the main
      site of neurodegeneration, but the expression pattern is broader than expected
      from the pathology of the disease. Frataxin mRNA is predominantly expressed in
      tissues with a high metabolic rate, including liver, kidney, brown fat and heart.
      We found that mouse and yeast frataxin homologues contain a potential
      mitochondrial targeting sequence in their N-terminal domains and that disruption
      of the yeast gene results in mitochondrial dysfunction. Finally, tagging
      experiments demonstrate that human frataxin co-localizes with a mitochondrial
      protein. Friedreich's ataxia is therefore a mitochondrial disease caused by a
      mutation in the nuclear genome.

PMID- 9241271
TI  - Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the
      frataxin homologue.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive degenerative disorder that
      primarily affects the nervous system and heart. Patients with FRDA have point
      mutations or trinucleotide repeat expansions in both alleles of FRDA, which
      encodes a protein termed frataxin. We show that the yeast frataxin homologue,
      which we have named YFH1, localizes to mitochondria and is required to maintain
      mitochondrial DNA. The YFH1-homologous domain of frataxin functions in yeast and
      a disease-associated missense mutation of this domain, or the corresponding
      domain in YFH1, reduces function. Our data suggest that mitochondrial dysfunction
      contributes to FRDA pathophysiology.

PMID- 9241272
TI  - Bcl-2 and Bax function independently to regulate cell death.
AB  - The BCL-2 family has various pairs of antagonist and agonist proteins that
      regulate apoptosis. Whether their function is interdependent is uncertain. Using
      a genetic approach to address this question, we utilized gain- and loss-of
      function models of Bcl-2 and Bax and found that apoptosis and thymic hypoplasia
      characteristic of Bcl-2-deficient mice are largely absent in mice also deficient
      in Bax. A single copy of Bax promoted apoptosis in the absence of Bcl-2. In
      contrast, overexpression of Bcl-2 still repressed apoptosis in the absence of
      Bax. While an in vivo competition exists between Bax and Bcl-2, each is able to
      regulate apoptosis independently.

PMID- 9241273
TI  - Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined
      by a single genetic locus.
AB  - Ischaemic stroke is a complex disorder caused by a combination of genetic and
      environmental factors. Clinical and epidemiological studies have provided strong
      evidence for genetic influences in the development of human stroke and several
      mendelian traits featuring stroke have been described. The genetic analysis of
      the non-mendelian, common ischaemic stroke in humans is hindered by the late
      onset of the disease and the mode of inheritance, which is complex, polygenic and
      multifactorial. An important approach to the study of such polygenic diseases is
      the use of appropriate animal models in which individual contributing factors can
      be recognized and analysed. The spontaneously hypertensive stroke-prone rat
      (SHRSP) is an experimental model of stroke characterized by a high frequency of
      spontaneous strokes as well as an increased sensitivity to experimentally induced
      focal cerebral ischaemia. Rubattu et al. performed a genomewide screen in an F2
      cross obtained by mating SHRSP and SHR, in which latency to stroke on Japanese
      rat diet was used as a phenotype. This study identified three major quantitative
      trait loci (QTLs), STR-1-3. Of these, STR-2 and 3 conferred a protective effect
      against stroke in the presence of SHRSP alleles and STR-2 co-localized with the
      genes encoding for atrial natriuretic and brain natriuretic factors. Our
      investigation was designed to identify the genetic component responsible for
      large infarct volumes in the SHRSP in response to a focal ischaemic insult by
      performance of a genome scan in an F2 cross derived from the SHRSP and the
      normotensive reference strain, WKY rat. We identified a highly significant QTL on
      rat chromosome 5 with a lod score of 16.6 which accounts for 67% of the total
      variance, co-localizes with the genes encoding atrial and brain natriuretic
      factor and is blood pressure independent.

PMID- 9241274
TI  - Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13
      restricted to 1.8 Mb.
AB  - Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a
      pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark
      of DBA is a selective decrease in erythroid precursors and anaemia. Other
      lineages are usually normal and the peripheral white blood cell count is normal.
      In approximately one-third of cases, the disease is associated with a wide
      variety of congenital anomalies and malformations. Most cases are sporadic, but
      10-20% of them follow a recessive or a dominant inheritance pattern. A female
      with DBA and a chromosomal translocation involving chromosome 19q was recently
      identified. We undertook a linkage analysis with chromosome 19 markers in
      multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin.
      Significant linkage to chromosome 19q13 was established for dominant and
      recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta =
      0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was
      identified in a patient with DBA. The deletion coincides with the translocation
      break-point and, together with key recombinations, restricts the DBA gene to a
      1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA
      is genetically homogeneous for a gene in 19q13.

PMID- 9241275
TI  - Mutations in the hair cortex keratin hHb6 cause the inherited hair disease
      monilethrix.
AB  - Pathogenic mutations in a large number of human epithelial keratins have been
      well characterized. However, analogous mutations in the hard alpha-keratins of
      hair and nail have not yet been described. Monilethrix is a rare autosomal
      dominant hair defect with variable expression. Hairs from affected individuals
      show a beaded structure of alternating elliptical nodes and constrictions
      (internodes). These internodes exhibit a high prospensity to weathering and
      fracture. Strong evidence that trichocyte keratin defects might underlie this
      hair disorder was provided by genetic linkage analyses that mapped this disease
      to the type-II keratin gene cluster on 12q13. All affected individuals from a
      four-generation British family with monilethrix, previously linked to the type-II
      keratin gene cluster, as well as three unrelated single monilethrix patients,
      exhibited a heterozygous point mutation in the gene for type-II hair cortex
      keratin hHb6, leading to lysine substitution of a highly conserved glutamic acid
      residue in the helix termination motif (Glu 410 Lys). In a three-generation
      French family with monilethrix of a milder and variable phenotype, we detected
      another heterozygous point mutation in the same glutamic acid codon of hHb6,
      which resulted in a conservative aspartic acid substitution (Glu 410 Asp). These
      mutations provide the first direct evidence for involvement of hair keratins in
      hair disease.

PMID- 9241276
TI  - Somatic mutation of the MEN1 gene in parathyroid tumours.
AB  - Primary hyperparathyroidism is a common disorder with an annual incidence of
      approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is
      caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are
      caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1;
      ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown.
      Parathyroid adenomas are usually monoclonal, suggesting that one important step
      in tumour development is a mutation in a progenitor cell. Approximately 30% of
      sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic
      markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the
      question of whether such sporadic parathyroid tumours are caused by sequential
      inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene
      and identified MEN1 germline mutations in fourteen of fifteen kindreds with
      familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with
      MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among
      33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1
      germline sequence was normal in each patient. All tumours with MEN1 gene mutation
      showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant
      allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic
      MEN1 gene mutation contributes to tumorigenesis in a substantial number of
      parathyroid tumours not associated with the MEN1 syndrome.

PMID- 9241277
TI  - Mutations in the cardiac troponin I gene associated with hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the
      young, is an autosomal dominant disease characterized by ventricular hypertrophy
      accompanied by myofibrillar disarrays. Linkage studies and candidate-gene
      approaches have demonstrated that about half of the patients have mutations in
      one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac
      troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C
      (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin
      regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because
      all the known disease genes encode major contractile elements in cardiac muscle,
      we have systematically characterized the cardiac sarcomere genes, including
      cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in
      184 unrelated patients with HCM and found mutations in the cTnI gene in several
      patients. Family studies showed that an Arg145Gly mutation was linked to HCM and
      a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is
      the seventh HCM gene.

PMID- 9241278
TI  - Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter
      gene.
AB  - Although disorders of iron metabolism are prevalent, iron transport remains
      poorly understood. To address this problem, we undertook a positional cloning
      strategy to identify the causative mutation in mice with microcytic anaemia (mk).
      Homozygous mk/mk mice have microcytic, hypochromic anaemia due to severe defects
      in intestinal iron absorption and erythroid iron utilization. We report the
      identification of a strong candidate gene for mk, and suggest that the phenotype
      is a consequence of a missense mutation in Nramp2 (ref. 5), a previously
      identified gene of unknown function. Nramp2 is homologous to Nramp1, a gene
      activa in host defense. If Nramp2 is mk, as the cumulative evidence suggests, our
      findings have broad implications for the understanding of iron transport and
      resistance to intracellular pathogens.

PMID- 9241279
TI  - Sound-induced seizures in serotonin 5-HT2c receptor mutant mice.
AB  - The epilepsies are a heterogeneous collection of seizure disorders with a
      lifetime expectancy risk rate of 2-4%. A convergence of evidence indicates that
      heritable factors contribute significantly to seizure susceptibility. Genetically
      epilepsy-prone rodent strains have been frequently used to examine the effect of
      genetic factors on seizure susceptibility. The most extensively studied of these
      have been strains that are susceptible to sound-induced convulsions (audiogenic
      seizures, or AGSs). Early observations of the AGS phenomenon were made in the
      laboratory of Dr. Ivan Pavlov; in the course of appetite-conditioning experiments
      in mice, the loud bell used to signal food presentation unexpectedly produced
      seizures in some animals. In 1947, DBA/2 (D2) mice were found to exhibit a
      genetic susceptibility to AGSs stimulated by a doorbell mounted in an iron tub.
      Since this discovery, AGSs have been among the most intensively studied
      phenotypes in behavioural genetics. Although several genetic loci confer
      susceptibility to AGSs, the corresponding genes have not been cloned. We report
      that null mutant mice lacking serotonin 5-HT2C receptors are extremely
      susceptible to AGSs. The onset of susceptibility is between two and three months
      of age, with complete penetrance in adult animals. AGS-induced immediate early
      gene expression indicates that AGSs are subcortical phenomena in auditory
      circuits. This AGS syndrome is the first produced by a known genetic defect; it
      provides a robust model for the examination of serotoninergic mechanisms in
      epilepsy.

PMID- 9241280
TI  - Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine
      hypoplasia and growth retardation after weaning.
AB  - 1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D,
      has roles in many biological phenomena such as calcium homeostasis and bone
      formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor
      (VDR), a member of the nuclear hormone receptor superfamily. However, the
      molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role
      during development and VDR genetic polymorphisms for predicting bone mineral
      density are uncertain. To investigate the functional role of VDR, we generated
      mice deficient in VDR by gene targeting. We report here that in VDR null mutant
      mice, no defects in development and growth were observed before weaning,
      irrespective of reduced expression of vitamin D target genes. After weaning,
      however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia
      and infertility, and bone formation was severely impaired as a typical feature of
      vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease,
      most of the null mutant mice died within 15 weeks after birth, and uterine
      hypoplasia with impaired folliculogenesis was found in female reproductive
      organs. These defects, such as alopoecia and uterine hypoplasia, were not
      observed in vitamin D-deficient animals. The findings establish a critical role
      for VDR in growth, bone formation and female reproduction in the post-weaning
      stage.

PMID- 9241281
TI  - atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in
      resistance to acute radiation toxicity.
AB  - Mutations in atm and p53 cause the human cancer-associated diseases ataxia
      telangiectasia and Li-Fraumeni syndrome, respectively. The two genes are believed
      to interact in a number of pathways, including regulation of DNA damage-induced
      cell-cycle checkpoints, apoptosis and radiation sensitivity, and cellular
      proliferation. Atm-null mice, as well as those null for p53, develop mainly T
      cell lymphomas, supporting the view that these genes have similar roles in
      thymocyte development. To study the interactions of these two genes on an
      organismal level, we bred mice heterozygous for null alleles of both atm and p53
      to produce all genotypic combinations. Mice doubly null for atm and p53 exhibited
      a dramatic acceleration of tumour formation relative to singly null mice,
      indicating that both genes collaborate in a significant manner to prevent
      tumorigenesis. With respect to their roles in apoptosis, loss of atm rendered
      thymocytes only partly resistant to irradiation-induced apoptosis, whereas
      additional loss of p53 engendered complete resistance. This implies that the
      irradiation-induced atm and p53 apoptotic pathways are not completely congruent.
      Finally-and in contrast to prior predictions-atm and p53 do not appear to
      interact in acute radiation toxicity, suggesting a separate atm effector pathway
      for this DNA damage response and having implications for the prognosis and
      treatment of human tumours.

PMID- 9241282
TI  - Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression
      of DMAHP.
AB  - Myotonic dystrophy, or dystrophia myotonica (DM), is an autosomal dominant
      multisystem disorder caused by the expansion of a CTG trinucleotide repeat in the
      3' untranslated region of the DMPK protein kinase gene on chromosome 19q13.3
      (refs 1-3). Although the DM mutation was identified more than five years ago, the
      pathogenic mechanisms underlying this most prevalent form of hereditary adult
      neuromuscular disease remain elusive. Previous work from our laboratory
      demonstrated that a DNase l-hypersensitive site located adjacent to the repeats
      on the wild-type allele is eliminated by repeat expansion, indicating that large
      CTG-repeat arrays may be associated with a local chromatin environment that
      represses gene expression. Here we report that the hypersensitive site contains
      an enhancer element that regulates transcription of the adjacent DMAHP homeobox
      gene. Analysis of DMAHP expression in the cells of DM patients with loss of the
      hypersensitive site revealed a two- to fourfold reduction in steady-state DMAHP
      transcript levels relative to wild-type controls. Allele-specific analysis of
      DMAHP expression showed that steady-state transcript levels from the expanded
      allele were greatly reduced in comparison to those from the wild-type allele.
      Together, these results demonstrate that CTG-repeat expansions can suppress local
      gene expression and implicate DMAHP in DM pathogenesis.

PMID- 9241283
TI  - Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking
      DMAHP gene.
AB  - Myotonic dystrophy, or dystrophia myotonica (DM), is a highly variable
      multisystem disease in which the classic adult-onset form displays progressive
      muscle wasting, cataracts, heart block, gonadal atrophy, insulin resistance and
      neuropsychiatric impairment. Its genetic basis is an expansion of CTG
      trinucleotide repeats in the DMPK protein kinase gene. Among the triplet repeat
      expansion disorders, DM is distinguished by the extended length of the repeat
      tract (5-13 kb in postmortem tissue) and its location in the 3' untranslated
      region of the gene that contains it. The pathophysiological mechanism for
      multisystem degeneration in DM is not understood. In contrast to the profound
      muscle wasting that characterizes advanced DM, only minor histopathological
      abnormalities have occurred in DMPK knockout mice or in mice that overexpress a
      human DMPK transgene, making it unlikely that changes in DMPK activity provide a
      unitary explanation for the disease. A DNAse hypersensitive site that maps 0.7 kb
      downstream (centromeric) from the CTG repeats is eliminated on DM chromosomes.
      This finding indicates that the repeat expansion may alter the adjacent chromatin
      structure and raises the possibility that it may also affect the expression of
      flanking genes. An interesting candidate flanking gene is DMAHP, a recently
      discovered homeodomain-encoding gene. We show here that DMAHP expression in
      myoblasts, muscle and myocardium is reduced by the DM mutation is cis, and the
      magnitude of this effect depends on the extent of CTG repeat expansion. These
      observations support the hypothesis that DMAHP participates in the
      pathophysiology of DM.

PMID- 9241284
TI  - A randomized controlled trial of the effect of third-trimester calcium
      supplementation on maternal hemodynamic function.
AB  - OBJECTIVE: To determine the effect of third-trimester calcium supplementation on
      maternal hemodynamic function. METHODS: Pregnant women were randomized to receive
      either 1.5 g of elemental calcium or placebo for 6 weeks during the third
      trimester. Using Doppler technique, maternal hemodynamic characteristics were
      measured at baseline, at 2 hours after the first dose of study drug, and at the
      completion of 6 weeks. Serum, dietary, and urinary calcium levels were also
      assessed. Power calculation indicated the need to study ten subjects in each
      group to detect a 1.2 L (20%) difference in cardiac output between groups,
      assuming a mean of 6.2 +/- 1.0 L/minute. Data were analyzed by analysis of
      variance for repeated measures, Student t test, Mann-Whitney U test, and Fisher
      exact test. RESULTS: Twenty-three women enrolled, and 18 completed the study.
      There were no statistically significant differences in demographic
      characteristics or in serum, dietary, or urinary calcium levels between the two
      groups. There were also no statistically significant differences in hemodynamic
      function over time within the calcium supplementation or placebo group (P > .05;
      analysis of variance for repeated measures). After 6 weeks, there were no
      significant differences between the calcium- and placebo-treated subjects in any
      hemodynamic measurement. Specifically, there was not a statistically significant
      difference in cardiac output (7.3 +/- 1.2 L/minute versus 8.0 +/- 0.9 L/minute; P
      = .09) between the calcium- and placebo-treated groups. CONCLUSION: These
      findings suggest that third-trimester calcium supplementation does not
      significantly alter cardiac output. The mechanism by which calcium
      supplementation lowers blood pressure remains to be elucidated.

PMID- 9241285
TI  - Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant
      teenagers.
AB  - OBJECTIVE: To determine whether increased calcium intake (2 g/day) in pregnancy
      is effective in reducing the risk of preeclampsia in pregnant teenagers. METHODS:
      The present study was a prospective, randomized, double-blind, controlled
      clinical trial. Two hundred sixty teenaged pregnant girls attending the Hospital
      Gineco-Obstetrico Isidro Ayora in Quito, Ecuador, were included. Selection
      criteria were age less than 17.5 years, nulliparity, first prenatal visit before
      20 weeks' gestation, and residency in Quito (2800-m altitude). We used a table of
      random numbers to assign 125 girls to receive 2000 mg of elemental calcium daily,
      beginning at 20 weeks of gestation and continuing until delivery; 135 women in
      the control group received a placebo. Blood pressure (BP) was measured twice
      every 4 weeks until delivery and at 48 hours after delivery. The diagnosis of
      preeclampsia was defined as BP greater than 140/90 mmHg on at least two occasions
      more than 6 hours apart and proteinuria greater than 30 mg/dL (over one cross by
      dipstick on two occasions 4-24 hours apart). RESULTS: The average daily calcium
      intake in this population was approximately 51% of the Recommended Dietary
      Allowance. Calcium supplementation was associated with a significantly decreased
      risk of preeclampsia (risk reduction 12.35%; P < .001), with 3.2% (n = 4)
      developing preeclampsia in the treatment group versus 15.5% (n = 21) in the
      placebo group. Moreover, calcium supplementation led to a reduction in systolic
      BP of 9.1 mmHg and in diastolic BP of 6.0 mmHg. CONCLUSION: These results suggest
      that calcium supplementation during pregnancy in populations with low calcium
      intake is a safe, effective, and inexpensive preventive measure that
      significantly reduces the risk of preeclampsia.

PMID- 9241286
TI  - Elevated homocyst(e)ine levels with preeclampsia.
AB  - OBJECTIVE: To determine whether homocyst(e)ine, a relatively new risk factor for
      possible endothelial cell dysfunction and premature vascular disease, is elevated
      in nulliparous pregnant women with preeclampsia. METHODS: We measured plasma
      homocyst(e)ine, folic acid, and vitamin B12 levels in 40 nulliparas, 20 with and
      20 without preeclampsia at the time of their delivery. RESULTS: Mean (+/-
      standard deviation) plasma homocyst(e)ine levels in the 20 nulliparous women with
      preeclampsia were significantly higher than in the 20 nulliparous women without
      preeclampsia (8.66 +/- 3.05 versus 4.99 +/- 1.11 mumol/L, P < .001). Folic acid
      and vitamin B12 concentrations were not significantly different between the two
      groups. CONCLUSION: Homocyst(e)ine levels are elevated in pregnant nulliparas
      with preeclampsia at the time of their delivery. Further studies are necessary to
      determine what role homocyst(e)ine may play in the etiology of preeclampsia.

PMID- 9241287
TI  - Case-control study of risk factors for complicated eclampsia.
AB  - OBJECTIVE: To identify risk factors associated with complicated eclampsia.
      METHODS: Twenty-four patients with eclampsia complicated by intracerebral
      hemorrhage, pulmonary edema, renal, hepatic, or respiratory failure, disseminated
      intravascular coagulation, abruptio placentae, pulmonary aspiration, or
      hemolysis, elevated liver enzymes, low platelets syndrome were compared
      retrospectively with 101 uncomplicated eclamptic controls. Information on
      maternal demographic factors, medical and obstetric histories, and maternal and
      perinatal outcomes was retrieved and analyzed by univariate and multivariate
      analysis. RESULTS: By multiple logistic regression, the only risk factors
      associated with the development of complicated eclampsia were maternal age over
      26 years (adjusted odds ratio [OR] 6.3, 95% confidence interval [CI] 2.17,
      18.48), multiparity (adjusted OR 4.5, 95% CI 1.55, 13.60) and no prenatal care
      (adjusted OR 3.3, 95% CI 1.25, 9.60). CONCLUSION: Maternal age above 26 years,
      multiparity, and no prenatal care are the maternal risk factors identified for
      the development of complicated eclampsia.

PMID- 9241288
TI  - Pharmacokinetics and pharmacodynamics of TRH during pregnancy.
AB  - OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of thyrotropin
      releasing hormone (TRH) in pregnant women. METHODS: Twenty-four pregnant and
      eight nonpregnant women were given 400 micrograms TRH as either intravenous
      infusion or bolus. Serial venous samples were collected for TRH, TSH, thyroxine,
      and prolactin assay. RESULTS: When given as bolus, mean (+/- standard error of
      the mean) peak plasma concentration (50 +/- 5.2 and 73 +/- 5.1 ng/mL, P < .01),
      elimination half life (4.3 +/- 0.3 and 6.3 +/- 0.4 minutes, P < .001), and area
      under the curve (156.4 +/- 14.8 and 340.1 +/- 32.8 ng/mL/minute, P < .001) in
      pregnant subjects were reduced compared with controls, whereas plasma clearance
      (45.4 +/- 6.5 and 23.6 +/- 2.1 mL/kg/minute, P < .01) and volume of distribution
      (27.8 +/- 1.8 and 19.0 +/- 1.3% body weight, P < .01) were increased. When given
      by infusion, steady-state concentration (6.6 +/- 0.5 and 9.8 +/- 0.9 ng/mL, P <
      .01) and elimination half-life (4.6 +/- 0.5 and 6.3 +/- 0.3 minutes, P < .05)
      were lower in pregnant subjects than in controls. Thyrotropin-releasing hormone
      kinetics were independent of mode of administration. Although basal TSH and
      thyroid hormone concentrations were similar in patients and controls, the TSH
      response to TRH was blunted in pregnant subjects compared with controls (9.3 +/-
      0.6 and 16.4 +/- 1.4 microIU/mL, P < .001). The basal (3187 +/- 488 and 147 +/-
      16 mIU/L) and maximal prolactin response (6193 +/- 426 and 1316 +/- 106 mIU/L)
      were increased in pregnant subjects compared with controls (P < .001).
      CONCLUSION: The peak plasma concentration and elimination half-life of TRH are
      reduced during pregnancy because of the increased volume of distribution and
      rapid clearance. Mode of administration does not affect TRH pharmacokinetics, but
      the maternal pharmacodynamic response differs in patients receiving bolus
      compared with infusion.

PMID- 9241289
TI  - Antepartum and intrapartum prediction of cesarean need: risk scoring in singleton
      pregnancies.
AB  - OBJECTIVE: To demonstrate the use of generalized additive logistic regression in
      the development of a risk-scoring system to predict cesarean delivery. METHODS:
      Women who delivered in the Prince of Wales Hospital, Hong Kong, from 1994 to 1995
      were the subjects of our study. Cases included were term singleton pregnancies
      with cephalic presentation, excluding those requiring cesarean delivery before
      labor. The cases were divided randomly into two sets. The prediction models were
      developed from set A and tested on set B, and vice versa. Maternal demographic
      and obstetric variables were used as potential predictors. Two models were
      formed, one before and one after the onset of labor. The generalized additive
      logistic regression was used to achieve optimal dichotomization of continuous
      measurements, and the predictive models were then developed. The validating
      results were pooled, represented, and compared as areas under receiver operating
      characteristic (ROC) curves. RESULTS: The first prediction model used maternal
      age, height, and weight at delivery as well as nulliparity, history of cesarean
      delivery, and the need for induction of labor. The second model had in addition
      the need for labor augmentation. The areas under the ROC curve for the models
      were 0.81 and 0.82, respectively, a statistically significant difference (z =
      5.75, P < .001). CONCLUSION: The use of generalized additive logistic regression
      optimizes dichotomization of continuous measurements and facilitates the
      development of precise and reproducible prediction models. Generalized additive
      logistic regression appears to be a useful tool, and its use is commended.

PMID- 9241290
TI  - Choice of second-trimester genetic sonogram for detection of trisomy 21.
AB  - OBJECTIVE: To determine the utilization rate of second-trimester genetic sonogram
      and its role in influencing the decision for amniocentesis in women at increased
      risk for fetal trisomy 21. METHODS: From November 1, 1993, to December 31, 1996,
      a second-trimester genetic sonogram or only genetic amniocentesis (as a first
      choice) were offered to pregnant women referred to our institution who were at
      increased risk for fetal trisomy 21. RESULTS: During the study period, 2089 women
      were referred to our unit for genetic prenatal diagnosis; of these, 1426 (68%)
      chose only genetic amniocentesis, and 663 (32%) chose a genetic sonogram as their
      first option. The yearly utilization rates of genetic sonogram were two of 477 or
      0.4% for 1993, 82 of 495 or 16.6% for 1994, 251 of 523 or 48.0% for 1995, and 328
      of 594 or 55.2% for 1996. Adjusting for potential confounders, multivariable
      logistic regression analysis showed that the most important factors associated
      with the women's decision to undergo genetic amniocentesis were three or more
      ultrasound markers present (relative risk [RR] 189.5, 95% confidence interval
      [CI] 37.1, 980.0), two ultrasound markers present (RR 47.2, 95% CI 9.8, 267.8),
      one ultrasound marker present (RR 12.7, 95% CI 5.5, 29.7), and abnormal serum
      biochemistry (RR 3.0, 95% CI 1.0, 8.9). CONCLUSION: The increasing utilization
      trend, in conjunction with the fact that an abnormal sonogram was the most
      influential factor in women's decision to undergo genetic amniocentesis, suggests
      that genetic sonogram services for detection of trisomy 21 should be added to the
      armamentarium of all prenatal diagnostic centers.

PMID- 9241291
TI  - Choroid plexus cysts: infant and early childhood developmental outcome.
AB  - OBJECTIVE: To determine the infant and early childhood developmental outcome
      associated with choroid plexus cysts diagnosed prenatally. METHODS: Between
      January 1990 and August 1995, 8270 women underwent second-trimester ultrasound
      examinations. All women whose fetuses were diagnosed as having choroid plexus
      cyst(s) underwent ultrasonographic detailed anatomy survey, were offered fetal
      karyotyping, and were followed with serial ultrasounds. Fetal karyotype,
      associated structural anomalies, maternal serum triple analyte screen, neonatal
      outcomes, and infant and early childhood developmental milestones were recorded.
      The children were followed subsequently, and developmental assessment was
      performed with a modified Denver II Developmental Screening Test. RESULTS: A
      diagnosis of choroid plexus cyst was made in 89 fetuses (1.1%). The mean (+/
      standard deviation [SD]) gestational age at diagnosis was 18.2 +/- 1.9 weeks
      (range 15-22). The cysts varied in size and laterality, with a mean (+/-SD) size
      of 5.9 +/- 3.3 mm (range 1-23). Three of the 61 women who underwent testing for
      fetal karyotype (4.9%) had abnormal karyotypes identified. All three karyotypes
      were trisomy 18, and all three trisomy 18 fetuses had additional sonographic
      abnormalities. All 28 women who chose not to undergo fetal karyotypic analysis
      delivered phenotypically normal infants. Infant and childhood developmental
      follow-up was performed on 76 children with cysts diagnosed prenatally. The mean
      (+/-SD) length of childhood follow-up was 35.5 +/- 16.2 months (range 12-82). All
      76 children were found to be developmentally normal by the Denver II
      Developmental Screening Test. CONCLUSION: These observations suggest that the
      finding of isolated choroid plexus cysts is not associated with delayed infant
      and early childhood development or an increased risk of abnormal karyotype. The
      presence of isolated choroid plexus cysts does not warrant intensive infant and
      early childhood follow-up.

PMID- 9241292
TI  - Teratologic evaluation of 178 infants born to mothers who attempted suicide by
      drugs during pregnancy.
AB  - OBJECTIVE: To identify the teratogenic risk of large doses of various drugs taken
      by women in attempting suicide. METHODS: This population-based, prospective,
      epidemiologic study involved 559 women with pregnancy verified by a serum
      pregnancy test who were admitted to the toxicologic inpatient clinic in Budapest
      responsible for providing health services to chemically poisoned individuals from
      a population of 3 million. Each self-poisoned woman was matched for age and
      gestational age with a control selected from among participants in
      periconceptional care. RESULTS: Two of 559 self-poisoned pregnant women died. One
      hundred seventy-eight infants born to mothers who poisoned themselves during
      pregnancy either were examined personally or had appropriate medical data
      available. After excluding eight infants with fetal alcohol syndrome born to
      heavy-drinking mothers, the rate of congenital abnormalities in study infants
      (9.0%) did not significantly exceed the rate of control infants (6.1%). Thus, no
      teratogenic effect of drugs used for self-poisoning could be identified, even
      though large doses of drugs were used in 27 cases between the 3rd and 8th weeks
      of fetal development. This sample was not large enough to evaluate single drugs
      separately. CONCLUSION: Drugs taken by women in attempting suicide do not seem to
      pose a risk for structural birth defects in the offspring.

PMID- 9241293
TI  - Oxytocin labor stimulation of twin gestations: effective and efficient.
AB  - OBJECTIVE: To test the hypothesis that oxytocin labor stimulation of twin
      gestations is similar to that of singletons regarding dosage, time,
      complications, and ability to achieve vaginal delivery. METHODS: This
      retrospective investigation included 124 gravidas receiving oxytocin for
      augmentation or induction of labor. Sixty-two women with twin gestations were
      matched by parity, cervical dilation at initiation of oxytocin, gestational age,
      oxytocin dosage regimen, and indications for oxytocin to controls with singleton
      pregnancies. Outcome variables included maximum dosage of oxytocin, incidence of
      hyperstimulation and fetal heart rate (FHR) abnormalities, time from oxytocin to
      delivery, cesarean deliveries, and maternal and neonatal outcomes. Statistical
      analysis was done using McNemar test, paired t test, and Wilcoxon signed-rank
      test for paired samples. RESULTS: Women with twin pregnancies and those with
      singletons responded similarly regarding maximum oxytocin dosage (21 +/- 1.5 and
      18 +/- 2.4 mU/minute, respectively, P = .1), time from oxytocin to delivery (7.0
      +/- 0.8 and 6.7 +/- 0.6 hours, respectively, P = .88), and successful vaginal
      delivery (90% and 90%, respectively). Oxytocin stimulation of twins resulted in
      fewer interruptions of the infusion for FHR abnormalities (5% compared with 26%,
      odds ratio [OR] 0.27, 95% confidence interval [CI] 0.16, 0.47) and
      hyperstimulation (6% compared with 18%, OR 0.19, 95% CI 0.36, 0.99). CONCLUSION:
      Twin gestation has no adverse impact on the effectiveness or efficiency of
      oxytocin labor stimulation. Twin pregnancy seems to be associated with fewer side
      effects.

PMID- 9241294
TI  - Umbilical artery Doppler velocimetry in fetuses with a single umbilical artery.
AB  - OBJECTIVE: Doppler waveform analysis of the umbilical artery is an important tool
      for the evaluation of high-risk pregnancies. Yet, available data are based on
      normal values from three-vessel umbilical cords. Our purpose was to evaluate the
      value of umbilical artery Doppler velocimetry in fetuses with a single umbilical
      artery. METHODS: One hundred thirteen consecutive singleton fetuses with a single
      umbilical artery between 16 and 40 weeks' gestational age were studied
      prospectively at a tertiary referral center for prenatal diagnosis and therapy.
      Complete follow-up was obtained from 103 cases. RESULTS: The systolic-diastolic
      ratio in the umbilical artery was abnormal in 31 fetuses (30%) and normal in 72
      fetuses (70%). Fetuses with abnormal Doppler waveform analysis in the umbilical
      artery were significantly more likely to be growth restricted (55 compared with
      15%), to have complex malformations (58 compared with 1%) or an abnormal
      karyotype (29 compared with 0%), or not to survive the fetal/perinatal period (42
      compared with 0%) than those with normal Doppler waveform analysis. CONCLUSION:
      Fetuses with a single umbilical artery and abnormal umbilical Doppler velocimetry
      had a significantly increased risk of adverse fetal and neonatal outcome compared
      with those with a single umbilical artery but normal Doppler studies.

PMID- 9241295
TI  - Uterine artery atherosclerotic disease: histologic features and clinical
      correlation.
AB  - OBJECTIVE: To determine whether uterine artery atherosclerosis is associated with
      known cardiovascular risk factors in women undergoing hysterectomy. METHODS:
      Seventy-four women undergoing hysterectomy between September 1995 and March 1996
      were evaluated. Following hysterectomy, samples of the uterine artery were
      collected for histologic evaluation. Plaque complexity and histologic
      measurements were compared with regard to known cardiovascular risk factors.
      RESULTS: Among the 59 premenopausal women, 55.9% had intimal thickening 40.7% had
      simple plaques, and 3.7% had complex lesions in the uterine artery samples. Among
      postmenopausal women, 40% had intimal fibrosis, 20% had simple plaques, and 40%
      had complex lesions. Postmenopausal status was correlated strongly with the
      presence of advanced atherosclerotic disease (P < .001). Postmenopausal women had
      significantly greater intimal area (P = .01), intimal area/medial area (P =
      .002), intimal area/vessel area (P = .002), maximal intimal thickness/medial
      thickness (P = .01), and significantly less medial thickness (P < .001). A
      significant linear correlation existed between age and the intimal/medial ratio
      among premenopausal women (P = .04) and postmenopausal women (P = .01). Patients
      with electrocardiogram (ECG) abnormalities had significantly greater
      intimal/medial area as well (P = .02). Hypertension was associated with complex
      lesions among the postmenopausal patients (P = .01). Preoperative cholesterol
      levels greater than 200 mg/dL were associated with greater intimal thickness (P =
      .05) and intimal thickness/medial thickness (P = .03). CONCLUSION: The severity
      of uterine artery atherosclerosis is significantly correlated with known risk
      factors for cardiovascular disease: increasing age, postmenopausal status, ECG
      abnormalities, and hypertension. Uterine artery histologic analysis may provide a
      means of assessing the degree of atherosclerosis in other, critical, vascular
      beds.

PMID- 9241296
TI  - Effect of abdominal vibroacoustic stimulation on sound and acceleration levels at
      the head of the fetal sheep.
AB  - OBJECTIVE: To measure the vibratory response of the fetal head and abdominal wall
      in sheep during vibroacoustic stimulation. METHODS: A piezoresistive
      accelerometer was attached to the skulls of seven sheep fetuses (128-134 days'
      gestational age), and a miniature hydrophone was attached to the skin overlying
      the fetal temporal bone. During fetal preparation and vibroacoustic stimulation
      procedures, ewes were anesthetized and supine. Vibroacoustic stimulation of the
      maternal abdomen was produced by each of two clinical devices that differed in
      spectral content, and an electric toothbrush. RESULTS: The approximate
      fundamental frequencies (f0) and first overtones (f1), as determined by both
      recordings of intrauterine sound pressure level and fetal head acceleration, were
      as follows: fetal acoustic stimulator, 75 and 150 Hz; electronic larynx, 150 and
      300 Hz; and electric toothbrush, 25 and 50 Hz, respectively. At fundamental
      frequencies and first overtones, the ranges of fetal head accelerations
      (expressed in 1/12-octave bands) were as follows: fetal acoustic stimulator, 10
      53 and 25-224 mm/sec2; electronic larynx, 10-53 and 18-114 mm/sec2; and electric
      toothbrush, 33-792 and 8-116 mm/sec2, respectively. Sound pressure levels
      exceeded 110 dB in all cases. High sound pressure levels in the uterus were
      proportional to fetal head vibration levels. CONCLUSION: Vibroacoustic
      stimulation of the surface of the abdomen of pregnant sheep is accompanied by
      both acoustic and vibratory exposure of the fetus.

PMID- 9241297
TI  - Delayed entry into prenatal care: effect of physical violence.
AB  - OBJECTIVE: To assess whether women who experienced physical violence by their
      partner during the 12 months before delivery were more likely to delay entry into
      prenatal care than were women who had not experienced physical violence. METHODS:
      We analyzed data from the Pregnancy Risk Assessment Monitoring System. The sample
      included 27,836 women who delivered live infants during 1993-1994 in nine states
      and were surveyed 2-6 months after delivery. We calculated risk ratios and 95%
      confidence intervals (CIs) to measure the association between physical violence
      within the 12 months before delivery and entry into prenatal care. RESULTS: The
      prevalence of delayed entry into prenatal care (entering after the first
      trimester) was 18.1% and that of reported physical violence was 4.7%. Overall,
      women who experienced physical violence were 1.8 times more likely (95% CI 1.5,
      2.1) to have delayed entry into prenatal care than women who had not experienced
      such violence. When stratifying by selected maternal characteristics, this
      association was found only for groups of women who were 25 years of age or older
      or were of higher socioeconomic status. CONCLUSION: Older women and women of
      higher socioeconomic status who reported physical violence were more likely to
      delay entry into prenatal care than younger or less affluent women.

PMID- 9241298
TI  - Hospitalizations for severe complications of pregnancy, 1987-1992.
AB  - OBJECTIVE: To compute ratios of severe pregnancy complications (the number of
      hospitalizations for pregnancy complications per 100 deliveries) and to examine
      factors associated with their prevalence. METHODS: Using population-based
      California hospital discharge data to estimate hospitalization ratios of
      pregnancy complications during 1987-1992, we defined cases by preselected
      pregnancy complication codes from the International Classification of Diseases,
      Ninth Revision, Clinical Modification, excluding induced abortions and delivery
      associated complications. All hospital deliveries of liveborn or stillborn
      infants were included in our denominator. We examined ratios by age, race
      ethnicity, payment source, total hospitalization charges, and length of hospital
      stay. RESULTS: There were 833,264 hospitalizations for pregnancy complications in
      California (25 complications per 100 deliveries), which included admissions for
      preterm labor (33%), genitourinary infection (16%), and pregnancy-induced
      hypertension (15%). Age-specific ratios were highest for women 14 years old and
      younger (38 per 100 deliveries) and lowest for women 25-29 years old (23 per 100
      deliveries). Ratios of complications varied by race-ethnicity; black women had
      the highest (42 per 100 deliveries), and Asian-Pacific Islander women had the
      lowest (21 per 100 deliveries). Ratios were unaffected by payment source. In
      1987, Medicaid charges were $118 million for 33% of the number of total
      hospitalizations for complications. In 1992, such Medicaid hospitalizations
      accounted for $356 million (49%) of the $734 million in total charges and for
      183,295 (45%) of the 409,000 total hospital days. CONCLUSION: Our results showed
      disparities in ratios of severe complications of pregnancy by age and race
      ethnicity as well as a shift of financial burden to Medicaid. These findings
      suggest that such complications may be reduced by identifying risk factors and
      targeting high-risk groups.

PMID- 9241299
TI  - Nifedipine and ritodrine in the management of preterm labor: a randomized
      multicenter trial.
AB  - OBJECTIVE: To compare the efficacy of nifedipine with ritodrine in the management
      of preterm labor. METHODS: One hundred eighty-five singleton pregnancies with
      preterm labor were assigned randomly to either ritodrine intravenously (n = 90)
      or nifedipine orally (n = 95). The principal outcome assessed was delay of
      delivery. RESULTS: Ritodrine was discontinued in 12 patients because of severe
      maternal side effects, and their results were excluded from further analysis.
      More women in the ritodrine group delivered within 24 hours (22 versus 11, P =
      .006), within 48 hours (29 versus 21, P = .03), within 1 week (45 versus 36, P =
      .009), and within 2 weeks (52 versus 43, P = .005) compared with those receiving
      nifedipine. There were significantly fewer maternal side effects in the
      nifedipine group. Apgar scores and umbilical artery and vein pHs were similar in
      both groups. The number of admissions to the neonatal intensive care unit (NICU)
      in the nifedipine group was significantly lower than in the ritodrine group (68.4
      versus 82.1%, P = .04). CONCLUSION: Nifedipine in comparison with ritodrine in
      the management of preterm labor is significantly associated with a longer
      postponement of deliver, fewer maternal side effects, and fewer admissions to the
      NICU.

PMID- 9241300
TI  - Induction of labor in the nineties: conquering the unfavorable cervix.
AB  - OBJECTIVE: To determine the efficacy, safety, and duration of induced labor using
      an integrative approach (prostaglandin, amniotomy, oxytocin) and to depict these
      findings graphically. METHODS: Five hundred ninety-seven pregnancies requiring
      induction of labor between October 1993 and May 1995 were analyzed prospectively.
      Patients were categorized by Bishop score at entry and by parity for comparison
      of success of induction, maternal and fetal complications, and duration of labor.
      RESULTS: The women who had a Bishop score at entry of 3 or less had significantly
      higher rates of failed induction (9.4 versus 0.7%, P < .01) and of cesarean
      delivery (29 versus 15.4%, P < .01) than those with a Bishop score above 3.
      Compared with spontaneous labor, the rates of cesarean delivery in induced labor
      remained significantly elevated. Complications of induction were infrequent,
      regardless of Bishop score. The time from initiation of induction to achievement
      of active phase was significantly longer in women with lower Bishop scores.
      CONCLUSION: Regardless of cervical status and parity, vaginal delivery can be
      anticipated in the majority of patients undergoing labor induction. The induction
      characteristics described may assist in the management of induced labor.

PMID- 9241301
TI  - Persistence of penicillin G benzathine in pregnant group B streptococcus
      carriers.
AB  - OBJECTIVE: To determine if streptococcicidal levels of penicillin G benzathine
      can be detected in maternal serum 4 weeks after treatment with 4.8 million units.
      METHODS: Thirty-seven pregnant women with positive group B streptococcus vaginal
      or urine cultures were each given 4.8 million units of penicillin G benzathine.
      Maternal blood samples were collected after injection and at delivery. Serum
      penicillin levels were measured by high-pressure liquid chromatography. Follow-up
      cultures were done when possible. RESULTS: None of the patients had serum
      penicillin levels below 0.20 microgram/mL 30 days after treatment. Cord blood
      levels were approximately 50% lower than maternal levels. In all but three
      subjects, cord blood levels exceeded 0.06 microgram/mL, the minimal inhibitory
      concentration for group B streptococcus. The three exceptions were patients who
      delivered more than 100 days after treatment. Group B streptococcus cultures were
      negative at the time of delivery in 72% of cases. None of the patients with
      positive cultures were moderately or heavily colonized. CONCLUSION: In pregnant
      women, penicillin G benzathine levels are high enough to inhibit the growth of
      group B streptococcus for more than 4 weeks after injection with 4.8 million
      units. Further studies are needed to evaluate whether this regimen can prevent
      neonatal colonization and invasive group B streptococcus disease.

PMID- 9241302
TI  - Differences in the estrogen content of breast adipose tissue in women by
      menopausal status and hormone use.
AB  - OBJECTIVE: To determine the levels of free estrone (E1) and estradiol (E2) in
      breast adipocytes of premenopausal women, premenopausal women using oral
      contraceptives (OCs), postmenopausal women, and postmenopausal women using
      estrogen replacement therapy (ERT). METHODS: Breast adipose tissue was obtained
      from 36 premenopausal and 29 postmenopausal women, and adipocytes were separated
      from stromal and epithelial cells through collagenase digestion and
      centrifugation. Oil was rendered from adipocytes, and E1 and E2 levels were
      measured by specific radioimmunoassays after extraction with methanol-water.
      RESULTS: Estrone and E2 levels were approximately 2.4- and 7.8-fold higher,
      respectively, in premenopausal women than in postmenopausal women. In
      premenopausal women, E1 and E2 correlated with the time since last menses (R2 =
      .55 and .62, respectively), whereas in postmenopausal women, E1 and E2 correlated
      with body mass index (BMI) (r = .48 and .52, respectively). Estrone levels were
      always greater than E2 levels in adipocytes, with the E1/E2 ratio being 2.7-fold
      higher in postmenopausal women than in premenopausal women. The use of OCs
      decreased E1 and E2 levels in premenopausal women, and ERT increased levels in
      postmenopausal women. CONCLUSION: Free estrogen in breast adipocytes is
      characterized by E1 dominance, with levels in premenopausal women correlating
      with the menstrual cycle and levels in postmenopausal women correlating with BMI.

PMID- 9241303
TI  - A microlaparoscopic technique for Pomeroy tubal ligation.
AB  - OBJECTIVE: To evaluate the efficacy of performing Pomeroy tubal ligation using
      microlaparoscopic techniques. METHODS: Thirty-eight consecutive women desiring
      permanent sterilization underwent laparoscopic Pomeroy tubal ligation using small
      (2 or 5 mm) transumbilical laparoscopes and secondary midline sites (5 mm and 14
      gauge). The procedures were performed under general anesthesia (n = 28) or local
      anesthesia with conscious sedation (n = 10). RESULTS: The mean operative time +/-
      standard deviation (SD) in minutes was 33.0 +/- 10.3. The mean recovery time +/-
      SD in minutes was 104.3 +/- 41.6. There were no operative complications, and no
      cases required conversion from the microlaparoscopic technique to a traditional
      method. CONCLUSION: The results of this study indicate that the Pomeroy tubal
      ligation may be performed using microlaparoscopic techniques. Furthermore, in
      selected cases, this technique can be performed under local anesthesia in an
      outpatient setting.

PMID- 9241304
TI  - Immune compromise and prevalence of Candida vulvovaginitis in human
      immunodeficiency virus-infected women.
AB  - OBJECTIVE: To investigate the effect of human immunodeficiency virus (HIV)
      infection on vaginal yeast colonization and symptomatic vulvovaginitis and to
      explore the effects of immune compromise on these conditions in HIV-positive
      women. METHODS: Between September 1991 and May 1993, 223 HIV-positive women
      without AIDS-defining conditions were enrolled for prospective follow-up and
      compared with 289 HIV-negative women enrolled in a concurrent study. Standardized
      gynecologic assessment was carried out. RESULTS: Cultures from 81 of 223 (36%)
      HIV-positive women and 72 of 289 (25%) HIV-negative women were positive for any
      yeast. The most commonly isolated yeasts were Candida albicans and Torulopsis
      glabrata; the proportion of non-C albicans isolates (26%) did not differ by
      serostatus. The rates of C albicans colonization and vulvovaginitis among
      immunocompetent (CD4 count at least 500 cells/mm3) HIV-positive women did not
      differ from those among HIV-negative women. Among HIV-positive women, risks for
      colonization and for symptomatic vulvovaginitis were increased approximately
      threefold and fourfold respectively, in women with CD4 counts below 200 cells/mm3
      compared with either immunocompetent HIV-positive women or HIV-negative women.
      CONCLUSION: The yeast species isolated from HIV-positive and HIV-negative women
      were similar. Rates of vaginal colonization and vaginitis were similar among
      nonimmunocompromised HIV-positive women and HIV-negative women. Elevated rates of
      yeast colonization and vaginitis were not seen among this population of HIV
      infected women before immune compromise. Both vaginal colonization and
      symptomatic vaginitis increased with immune compromise among HIV-positive women,
      especially at CD4 counts below 200 cells/mm3.

PMID- 9241305
TI  - Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial
      resection in the treatment of dysfunctional uterine bleeding.
AB  - OBJECTIVE: To compare the effect of a levonorgestrel-releasing intrauterine
      device with that of endometrial resection on menstrual bleeding, patient
      satisfaction, and quality of life in menorrhagic women during 12 months of follow
      up. METHODS: Seventy premenopausal women with dysfunctional uterine bleeding were
      enrolled in a prospective, open, parallel-group, controlled trial. They were
      randomized to either insertion of an intrauterine system releasing 20
      micrograms/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The
      women were evaluated at baseline, and thereafter, uterine bleeding was assessed
      monthly with a pictorial blood loss assessment chart. Clinical gynecologic
      examination was performed bimonthly, and the hematologic variables were measured
      at 6 and 12 months. On the latter occasion, the women were requested to rate the
      degree of satisfaction with the effect of their treatment and to complete the
      Short Form 36 General Health Survey questionnaire. RESULTS: Recurrent menorrhagia
      was observed at 12 months in four women in the intrauterine device group
      (including two with partial expulsion of the device) and in three women in the
      resection group. Compared with baseline values, at 1 year, the pictorial blood
      loss assessment chart score was reduced by 79% in the former group and by 89% in
      the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the
      women with an intrauterine device compared with 71% who underwent endometrial
      resection. The degree of satisfaction with treatment was high in both groups,
      with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine
      device group versus 33 of 35 (94%) in the resection group. Health-related quality
      of life perception was not significantly different in the two treatment groups.
      CONCLUSION: Somewhat less satisfactory results were obtained with a
      levonorgestrel-releasing intrauterine system compared with endometrial resection
      for dysfunctional uterine bleeding at 1 year of follow-up.

PMID- 9241306
TI  - Menstrual characteristics in women with and without endometriosis.
AB  - OBJECTIVE: To assess menstrual blood loss and other menstrual characteristics
      prospectively in women with and without endometriosis. METHODS: Three hundred
      fifteen premenopausal women undergoing laparoscopy for various reasons were asked
      to complete a pictorial blood loss assessment chart devised by Higham et al to
      evaluate menstrual flow on which the monthly score has been demonstrated to
      correlate directly with uterine blood loss measured by the alkaline hematin
      method. In addition, cycle length and flow duration were recorded. The women also
      were asked to grade dysmenorrhea severity using a 100-mm visual analogue and a 0
      3-points verbal rating scale. RESULTS: One hundred sixty-three women had
      endometriosis, and 152 did not. The latter group comprised 59 women with a normal
      pelvis, 36 with nonendometriotic ovarian cysts, 29 with chronic pelvic
      inflammatory disease, and 28 with miscellaneous conditions. The median
      [interquartile range] pictorial blood loss assessment chart score was 110 [66.5
      156.5] in women with endometriosis and 84 [56-129] in those without the disease
      (P = .007); 87 out of 163 (53%) women with endometriosis had a menstrual chart
      score equal to or greater than 100 compared with 56 out of 152 (37%) of those
      without (chi 2(1) = 8.02, P = .005; difference = 16%, 95% confidence interval,
      6%, 28%). Menstrual flow duration was slightly longer in women with endometriosis
      (mean difference, 0.33 days). Dysmenorrhea visual analogue and verbal rating
      scores were significantly higher in the endometriosis than the nonendometriosis
      group. CONCLUSION: According to a visual chart, women with endometriosis had
      heavier menstrual flow and a significantly higher rate of abnormal menstrual
      scores that those without the disease.

PMID- 9241307
TI  - Hormone replacement therapy among Danish women aged 45-65 years: prevalence,
      determinants, and compliance.
AB  - OBJECTIVE: To study the prevalence and determinants of consultation for
      climacteric complaints and the prescription, commencement, and continuation of
      hormone replacement therapy (HRT) among women aged 45-65 years. METHODS: A cross
      sectional national survey was conducted in Denmark in November 1994 among 1459
      women. A total of 1015 women (response rate 69.6%) agreed to participate and
      provided questionnaire data. RESULTS: Of the women who had experienced
      climacteric complaints, 67.4% (95% confidence interval [CI] 63.3, 71.4%) had
      consulted a physician. More women consulted if their complaints were severe
      rather than slight-to-moderate (odds ratio [OR] 6.46). Within the total sample,
      33.4% of the women had been prescribed HRT at some time, and 94.1% of these women
      actually had started the treatment. Of the women who started the treatment, 66.3%
      reported that they still were using HRT at the time of the survey. The current
      HRT use rate among all respondents was 18.4% (95% CI 16.1, 20.9%). Women with
      severe or slight-to-moderate climacteric complaints more often reported having
      had HRT prescribed than women without complaints (OR 23.2 and 5.80,
      respectively). Furthermore, women who had had a hysterectomy with bilateral
      oophorectomy more often reported use than women with an intact uterus (OR 10.0).
      Hormone replacement therapy prescription was associated only weakly with
      osteoporosis concerns (OR 1.74). Its continuation decreased with age, was higher
      after hysterectomy and among women who regularly participated in sports or
      exercised, but was not (P > .05) related to osteoporosis concerns. Age-specific
      HRT continuation rates decreased among users who reported withdrawal bleeding (P
      < .05) but not among users who did not experience such bleeding (P > .05).
      CONCLUSION: In this survey, HRT had been used by one in three women at menopause,
      mainly for the alleviation of climacteric complaints and hardly ever because of
      osteoporosis concerns. Although it might be expected that HRT users who are
      concerned about developing osteoporosis in later life would be likely to continue
      the treatment for longer than other users, the study results did not bear this
      out. Continuation depended mainly on having had a hysterectomy and participation
      in sports and was higher among users with an intact uterus if they had had no
      withdrawal bleeding.

PMID- 9241308
TI  - Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer
      system for cervical cancer screening.
AB  - OBJECTIVE: To compare the cytologic diagnoses and specimen adequacy of a fluid
      based, thin-layer preparation and conventional Papanicolaou tests. METHODS: A
      total of 7360 women from six separate sites-three screening centers and three
      hospitals-participated in split-sample/matched-pair, double-masked clinical
      trials. A conventional Papanicolaou test was performed, after which residual
      material on the sampling device was rinsed into a fluid preservative from which a
      thin-layer slide (ThinPrep) was prepared using the ThinPrep 2000 automated slide
      processor (Cytyc Corp., Boxborough, MA). Conventional and ThinPrep slides were
      read independently. Cytologic diagnoses and specimen adequacy were classified
      using the Bethesda system. RESULTS: For the three screening centers, 65% more
      diagnoses of low-grade squamous intraepithelial lesions and higher were made on
      the ThinPrep slides (P < .001); for the three hospital centers, 6% more of these
      diagnoses were made with the ThinPrep method (P = .294). Comparison of specimen
      adequacy showed a significant increase in satisfactory specimens and a reduction
      in the number of "satisfactory but limited by" specimens using the ThinPrep
      method (P < .001). CONCLUSION: The fluid-based, ThinPrep method of sample
      preparation resulted in a statistically significant increase in cytologic
      diagnosis of cervical cancer precursors and in specimen adequacy compared with
      the conventional Papanicolaou testing method.

PMID- 9241309
TI  - Expression of midkine and pleiotropin in ovarian tumors.
AB  - OBJECTIVE: To compare the expression of midkine and pleiotropin in malignant
      ovarian tumors with that in normal and benign ovarian tissue. METHODS: Total RNA
      was isolated from 23 samples of normal ovaries, 15 benign ovarian tumors, and 36
      malignant ovarian tumors. Midkine and pleiotropin gene expression was examined by
      using Northern blot analysis. To confirm the localization of midkine expression,
      in situ hybridization and immunohistochemical analyses were performed. The
      truncated midkine messenger RNA was examined using polymerase chain reaction with
      complementary DNA synthesized from total RNA with reverse transcriptase. RESULTS:
      Expression of midkine gene was observed in 19 of 23 normal ovary samples and in
      51 of 53 ovarian tumors (13 of 15 benign, both of the two borderline tumors, and
      all 36 malignant tumors). Pleiotropin gene was expressed in six normal ovaries
      and in 24 tumors (nine benign, two borderline, and 13 malignant tumors). The
      expression of midkine in germ cell tumors was significantly lower than in
      epithelial tumors, whereas expression in malignant epithelial tumors was
      significantly higher than in benign ones. In germ cell tumors, two samples with
      differentiated neural tissues showed high levels of pleiotropin gene expression.
      In situ hybridization and immunohistochemical analysis showed strong expression
      of midkine in cancer cells. The truncated midkine messenger RNA was not found in
      any of the normal, benign, or malignant tissues examined. CONCLUSION: These
      results suggest an association between midkine and carcinogenesis. Expression of
      pleiotropin is more restricted, and high levels of its expression may be
      correlated with neural differentiation.

PMID- 9241310
TI  - Obstetrician-gynecologists as primary care physicians: the perspectives of health
      maintenance organization medical directors and obstetrician-gynecologists.
AB  - OBJECTIVE: To survey the interest of obstetrician-gynecologists in serving as
      primary care physicians and their perceived preparedness for that role from the
      view points of managed care plans and obstetrician-gynecologists. METHODS: A
      sample of obstetrician-gynecologists was asked to describe their preferred
      physician roles in managed care plans. Managed care medical directors were asked
      to define the obstetrician-gynecologist's role in their health plans. The mailed
      survey questions focused on 1) obstetrician-gynecologists' interest in serving as
      primary care physicians and/or gatekeepers, 2) direct access to obstetrician
      gynecologists, and 3) additional training needed to serve as primary care
      physicians. RESULTS: Thirty-seven percent of obstetrician-gynecologists expressed
      little or no interest in serving as primary care physicians, and 37% had some or
      high interest. Fifty-six percent were not interested in serving as gatekeepers,
      and 45% believed that physicians in the specialty should not do so. Almost all
      believed women should be allowed direct access to obstetrician-gynecologists.
      Over half of the managed care plans allowed women to refer themselves to
      obstetrician-gynecologists, and one-third allowed these physicians to serve as
      primary care gatekeepers. Most plans believed that extensive additional training
      is needed for obstetrician-gynecologists to serve as gatekeepers, whereas 70% of
      specialists believed that little or no additional training is needed. CONCLUSION:
      Obstetrician-gynecologists do not all agree on their appropriate and preferred
      role as physicians in the managed care environment; 37% see themselves as primary
      care physicians, whereas 37% would rather act as consultative specialists. Nearly
      all, however, support direct access to obstetrician-gynecologists. Most (69.7%)
      believe that they are capable of serving as primary care gatekeepers with little
      or no additional training, but managed care plans believe otherwise.

PMID- 9241312
TI  - The Vecchietti operation for constructing a neovagina: indications,
      instrumentation, and techniques.
AB  - The Vecchietti method is a surgical technique for the treatment of vaginal
      agenesis that constructs a dilation-type neovagina in 7-9 days. We have performed
      the Vecchietti operation on six patients. The method was applied to create a
      primary neovagina, to lengthen a surgically foreshortened vagina, and to
      reconstruct an obliterated neovagina with or without the presence of a uterus.
      Two patients underwent the conventional transabdominal approach, and four,
      laparoscopy. Follow-up was 7-39 months, and neovaginal depth was 8.0-10.6 cm. The
      anatomic and functional results in all patients were excellent.

PMID- 9241311
TI  - Treatment of depression by obstetrician-gynecologists: a survey study.
AB  - OBJECTIVE: We performed an exploratory survey of depression diagnosis, treatment,
      and patient referral patterns by Fellows of ACOG. We also examined obstetrician
      gynecologists' professional training in the management of clinical depression.
      METHODS: We sent a questionnaire to a total of 1370 ACOG Fellows. Sixty percent
      of the surveys were returned. RESULTS: As a group, obstetrician-gynecologists
      reported diagnosing an average of four new cases of depression per month. Within
      the overall sample, the number of new diagnoses of depression made each month was
      significantly greater for those defining themselves as primary care physicians
      than for those defining themselves as specialists. When treating depression
      pharmacologically, obstetrician-gynecologists reported that they overwhelmingly
      (74% of the time) chose selective serotonin reuptake inhibitor antidepressants.
      Ninety-five percent of obstetrician-gynecologists reported that they referred
      severely depressed patients to a mental health professional. A majority of
      respondents neither received residency training (80%) nor completed a continuing
      medical education course (60%) on the treatment of clinical depression in women.
      CONCLUSION: Obstetrician-gynecologists who describe themselves as primary care
      physicians make significantly more diagnoses of depression than those considering
      themselves specialists. Studies further to assess obstetrician-gynecologists'
      management of depression and better to define needs for professional education
      are warranted.

PMID- 9241313
TI  - A simple technique of securing inferior epigastric vessels and repairing the
      rectus sheath at laparoscopic surgery.
AB  - Trauma to the inferior epigastric artery during insertion of ports for
      laparoscopic surgery can be associated with major hemorrhage. Several techniques
      have been developed to deal with this emergency, but most require special and
      expensive instrumentation that may not be readily available. We describe a simple
      and quick method to deal with this complication using only standard sutures and a
      laparoscopic needle holder. Two sutures with straight needles are inserted below
      laterally and medially to the vessels and pulled out via a contralateral port.
      The sutures are tied together and pulled back into the abdominal cavity and tied
      to secure the vessels. The procedure is repeated above the vessels to produce
      complete hemostasis. The technique also can be applied easily to repair the
      rectus sheath after using large trocars and cannulas and thereby prevent
      herniation.

PMID- 9241314
TI  - Mullerian agenesis: an update.
AB  - Recently, many advances have been made in the study of sexual differentiation,
      including the discoveries of the gene for antimullerian hormone as well as the
      gene for its receptor. However, the etiology of the clinical syndrome of
      mullerian agenesis remains elusive. We hypothesize that activating mutations of
      either the antimullerian hormone gene or its receptor gene may cause mullerian
      duct regression in a genetic female during embryogenesis. This clinical
      commentary discusses the current management of the syndrome including the Abbe
      McIndoe procedure, the most commonly used method of surgical correction, and the
      Frank vaginal dilation method, the most common nonsurgical method of correction.

PMID- 9241315
TI  - Once a cesarean, always a controversy.
AB  - For most of this century, "once a cesarean, always a cesarean" was the rule in
      the United States. In the 1980s, vaginal birth after cesarean grew in popularity
      and the pendulum began to swing away from routine repeat cesarean delivery.
      Recently, the wisdom of this transition has been questioned. As the 20th century
      comes to a close, the treatment of the patient with a prior cesarean delivery
      remains controversial.

PMID- 9241316
TI  - Correlation between maximum cervical dilatation at cesarean delivery and
      subsequent vaginal birth after cesarean delivery.

PMID- 9241317
TI  - Correlation between maximum cervical dilatation at cesarean delivery and
      subsequent vaginal birth after cesarean delivery.

PMID- 9241318
TI  - Cost-effectiveness of strategies used in the evaluation of pregnancies
      complicated by elevated maternal serum alpha-fetoprotein levels.

PMID- 9241319
TI  - The effect of different sampling intervals on the measurement of intrapartum
      fetal heart rate variability.

PMID- 9241320
TI  - Performance of the dipalmitoyl phosphatidylcholine test in predicting respiratory
      distress syndrome in contaminated samples of amniotic fluid.

PMID- 9241322
TI  - Solitary rectal ulcer syndrome: stopping the prolapse heals the ulceration.
AB  - The solitary rectal ulcer syndrome is an uncommon condition in which a benign
      ulceration area develops in the rectum. There is evidence that the solitary
      rectal ulcer syndrome is associated with rectal prolapse either overt or occult.
      The place of surgery in the management of this condition is not yet clearly
      defined. The Authors report a case where the patient was managed surgically
      because of persistent severe complications. This case confirms that stopping even
      occult prolapse may lead to rapid healing of the solitary rectal ulcer.

PMID- 9241321
TI  - Aneurysms of the lower limbs: evaluation and management.
AB  - In order to evaluate the results of the conservative follow up vs surgical
      management of infra-inguinal aneurysms, a retrospective review of 23 patients
      with 28 peripheral aneurysms of the lower limbs was undertaken. Among them,
      common femoral (5 cases) and popliteal (16 cases) aneurysms were most frequent;
      superficial femoral (1) and tibial (1) aneurysms were isolated; 5 patients had
      bilateral aneurysms. The majority of symptomatic aneurysms presented local
      discomfort (4), acute (4) or chronic (8) ischaemia. Symptoms of nerve (2) or view
      (1) compression were less common. Duplex or Color-Doppler Scanning, angio-TC and
      MR confirmed the clinical diagnosis; arteriography demonstrated the number of
      patent distal vessels. Nine arterial aneurysms were kept under clinical and
      ultrasonographic observation; three patients were submitted to delayed surgical
      repair; a major amputation was required and two of these died of cardiac
      diseases. In the remaining sixteen cases, early elective surgical repair was
      performed, with resection or ligation of aneurysms. Two cases of acute limb
      ischaemia were submitted to successful limb-salvage procedures. A primary
      amputation was necessary in a case with irreversible ischaemia; a lumbar
      sympathectomy was performed in a patient with a poor run-off. Dacron (5 cases),
      PTFE (5 cases) or autologous saphenous vein (11 cases) grafts were used. No post
      operative complications or limb-loss occurred. Three patients died of myocardial
      infarction during the follow up period (mean 28 months). Authors' results suggest
      that early surgical repair of peripheral aneurysms of the lower limbs is the
      safest and most effective management.

PMID- 9241323
TI  - Biological basis for PCO2 as a detector of ischemia.

PMID- 9241324
TI  - The combination of external high-frequency oscillation and pressure support
      ventilation in acute respiratory failure.
AB  - BACKGROUND: Effective gas exchange can be maintained in animals by using external
      high-frequency oscillation (EHFO). The present study evaluates the effect of
      relatively long-term duration EHFO combined with pressure support ventilation
      (PSV) in patients with acute respiratory failure. METHODS: Twelve patients were
      ventilated with EHFO combined with PSV for 8 h at 60 oscillations.min-1, with a
      cuirass pressure of 36 cm H2O: -26 to +10 cm H2O (27 mm Hg: -19.5 to +7.5 mm Hg)
      and an inspiratory-to-expiratory ratio of 1:1. Blood gas values and hemodynamic
      parameters were measured. RESULTS: Significant increases were noted in cardiac
      index (3.0 +/- 0.7 to 3.2 +/- 0.7 1.min-1.m-2, P < 0.05) and stroke volume index
      (32 +/- 14 to 35 +/- 13 ml.m-2, P < 0.05) without changes in pulmonary artery
      wedge pressure at 1 h after EHFO. PaO2 (kPa)/FiO2 and PaCO2 improved from 21.9 +/
      7.5 to 26.8 +/- 8.0 (P < 0.05) at 2 h and from 6.9 +/- 1.7 to 6.1 +/- 0.9 (P <
      0.01) at 30 min after EHFO, respectively. Breath sounds could be heard well
      throughout the lung fields after institution of EHFO. The mucous rales also
      decreased. CONCLUSIONS: As a method of ventilation for patients with acute
      respiratory failure, EHFO combined with PSV may have potential advantages over
      conventional mechanical ventilation when drainage of secretions if facilitated.
      Beneficial effects of EHFO may appear after several hours.

PMID- 9241325
TI  - Delayed derecruitment after removal of PEEP in patients with acute lung injury.
AB  - BACKGROUND: A step decrease in positive end-expiratory airway pressure (PEEP) is
      not followed by an instantaneous loss of the PEEP-induced increase in end
      expiratory lung volume (EELV). Rather, the reduction of EELV is delayed, while
      adverse PEEP effects on hemodynamics are immediately attenuated upon the drop in
      airway pressure. Step PEEP increments were applied to the lungs of patients with
      acute lung injury. It was investigated retrospectively whether enlargement of end
      expiratory lung volume and changes in lung mechanics persist 45 min after removal
      of the PEEP increment. METHODS: In 14 patients with acute lung injury (LIS score
      2.7) EELV and volume-dependent dynamic compliance of the respiratory system
      (Cdyn,rs) were determined 45 min after removal of an additional PEEP increment
      (0.64 kPa added to baseline PEEP of 1.0 kPa). RESULTS: Nine patients kept an EELV
      gain of 13% (SD 7) and showed improved Cdyn,rs. In 5 patients, EELV was reduced
      (by 9% (SD 6)) and Cdyn,rs unchanged after removal of the PEEP increment compared
      to baseline. CONCLUSION: A subgroup of patients with acute lung injury, the
      characteristics of which remain to be defined, benefit from prolonged recruitment
      effects up to 45 min after removal of a PEEP increment, while sequelae of
      continuously increased airway pressures are minimised.

PMID- 9241326
TI  - Atrial natriuretic peptide and N-terminal atrial natriuretic peptide in plasma
      reflect right ventricular volumes following coronary artery surgery.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) and the more stable N-terminal
      fragment (N-ANP) of prohormone are peptides, released in equimolar amounts from
      cardiac myocytes in response to atrial stretch or ventricular overload and
      myocardial ischaemia. Protection of the right ventricular (RV) myocardium during
      ischaemia in cardiac surgery is difficult, especially in patients with severe
      right coronary artery (RCA) disease. This prospective study was designed to
      ascertain a possible relationship between changes in plasma ANP/N-ANP
      concentration and RV function in RCA-diseased patients. METHODS: Plasma ANP and N
      ANP concentrations and RV function, measured by fast-response thermodilution,
      were determined serially in 15 patients with total RCA stenosis and in another 15
      with no significant RCA disease (controls) before, during and after coronary
      surgery. RESULTS: The RV ejection fraction was lower and the RV end-systolic
      volume index higher in the RCA-diseased patients than in the controls (P < 0.05)
      on the second postoperative day, and both ANP and N-ANP were higher in the RCA
      patients (P < 0.05) from 6 h after cardiopulmonary bypass till the second
      postoperative day. At the same time the changes in N-ANP concentrations from the
      levels before induction of anaesthesia correlated with RV ejection fraction and
      RV volume indexes, but not with heart rate or parameters indirectly reflecting
      left-sided loading. Right atrial pressure did not differ between the groups nor
      did it increase significantly during the study. CONCLUSIONS: The relationships
      found between N-ANP and RV volume indexes and RV ejection fraction suggest
      ventricular expression of ANP: ANP release may be stimulated by RV distension,
      the more so the poorer the RV function.

PMID- 9241327
TI  - Mivazerol, a new alpha 2-adrenergic agonist, blunts cardiovascular effects
      following surgical stress in pentobarbital-anesthetized rats.
AB  - BACKGROUND: Mivazerol is a new and selective alpha 2-adrenoceptor agonist, devoid
      of hypotensive effects, which has been designed to prevent adverse cardiac
      outcome in perioperative patients with, or at risk coronary artery disease.
      METHODS: In the present study, the effects of mivazerol on hemodynamic changes
      induced by trachea-exposure surgery stress were investigated in pentobarbital
      anesthetized rats, and compared to those of dexmedetomidine. RESULTS: Intravenous
      infusion of 3 different doses of mivazerol (3.75, 7.5 and 15 micrograms.kg-1.h-1)
      did not significantly alter BP but caused a dose-related decrease in HR. The
      maximal decrease in HR was approximately 87 beats/min. Contrary to mivazerol,
      dexmedetomidine (7.5 micrograms.kg-1.h-1, i.v.) decreased both BP (11 +/- 3.2
      mmHg) and HR. The maximum decrease in HR was approximately 104 beats/min.
      Surgical stress produced a rapid increase in BP (maximal increase of 50 mmHg) and
      HR (maximal increase of 100 beats/min), which lasted for at least 15 min.
      Constant infusion of mivazerol, at dose of 15 micrograms.kg-1.h-1, beginning 20
      min prior to surgery and lasting for 35 min, significantly inhibited surgical
      stress-induced increases in BP (P < 0.05) and HR (P < 0.001). Dexmedetomidine, at
      a dose which produced hypotension and profound bradycardia prior to surgery, did
      not have any effect on the surgical stress-induced elevation in BP (P > 0.05),
      but prevented the increase in HR (P < 0.05). Pretreatment with the alpha 2
      adrenoceptor antagonist rauwolscine (0.5 mg/kg, i.v.) blocked the bradycardia
      induced by mivazerol as well as the inhibitory effect of mivazerol on surgical
      stress-induced elevations in HR and BP. CONCLUSION: Mivazerol attenuates surgical
      stress-induced elevations in BP and HR during pentobarbital anesthesia in rats,
      and these effects are mediated by stimulation of alpha 2-adrenoceptors. Unlike
      dexmedetomidine, mivazerol does not reduce BP, and is also more potent than
      dexmedetomidine in blunting surgical stress-induced increases in BP in
      pentobarbital-anesthetized rats.

PMID- 9241328
TI  - Beneficial effects of the prone position on the incidence of barotrauma in oleic
      acid-induced lung injury under continuous positive pressure ventilation.
AB  - BACKGROUND: Factors that contribute to ventilator-induced barotrauma are not well
      defined. This study investigates the effects of posture on ventilator-induced
      barotrauma, as well as arterial oxygenation. METHODS: Twelve dogs with oleic acid
      lung injury, lying in the prone position (n = 6) and right lateral position (n =
      6), were mechanically ventilated with continuous positive pressure ventilation
      for 24 hours. The incidence of pneumothorax and arterial oxygenation were
      investigated in each position. RESULTS: All animals lying in the lateral position
      developed pneumothorax in the nondependent thorax, while only one animal in the
      prone position developed pneumothorax in the left thorax (P < 0.05). Postmortem
      examination revealed that in the lateral group, the nondependent lung consisted
      of large areas of emphysematous regions and neutrophil infiltration regions,
      while the dependent lung was composed of extensive atelectasis and neutrophil
      infiltration. Lung ruptures occurred in the nondependent lung at the regions of
      either emphysematous change or severe neutrophil infiltration. In the prone
      group, in contrast, both lungs were inflated fairly homogeneously with only small
      areas of atelectatic and emphysematous changes. In the dog in whom pneumothorax
      developed, lung ruptures were limited to the regions of severe neutrophil
      infiltration in the left lung. No animal in either group had a peak airway
      pressure more than 20 cmH2O. The peak airway pressures were 17.5 +/- 1.3 cmH2O in
      the lateral group and 16.6 +/- 2.1 cmH2O in the prone group (P > 0.05). Tidal
      volume was comparable between the lateral group (13 +/- 2 ml/kg) and the prone
      group (12 +/- 1 ml/kg) before pneumothorax occurred (P > 0.05). Arterial
      oxygenation was much better in the prone group than in the lateral group during
      the experiment (P < 0.05). CONCLUSION: It was concluded that in lung injury dogs,
      the prone position has beneficial effects on the incidence of ventilator-induced
      barotrauma and arterial oxygenation when compared with the lateral position.
      Ventilator-induced barotrauma may occur at lower airway pressure.

PMID- 9241329
TI  - Impedance cardiography in cardiac surgery patients: abnormal body weight gives
      unreliable cardiac output measurements.
AB  - BACKGROUND: To study the accuracy of cardiac output measurement by means of
      Electrical Impedance Cardiography (EIC) in post-cardiac surgery patients.
      METHODS: In a prospective study, we compared cardiac output measurements by means
      of thermodilution (COTD) with impedance cardiographic-derived values (COEIC) in
      37 mechanically ventilated patients after cardiac surgery. Both methods were used
      simultaneously. RESULTS: COEIC values were weakly correlated with COTD in the
      total group when the equation of Sramek-Bernstein was employed to calculate COEIC
      (r = 0.60, P < 0.001, mean difference and standard deviation: -0.06 +/- 1.25
      l.min-1). After exclusion of the 12 patients whose body weight differed > 15%
      from their ideal body weight, no significant difference was found between the
      mean values (5.40 +/- 1.80 l.min-1 (COEIC) vs 5.31 +/- 1.69 l.min-1, n = 25)
      while the correlation coefficient increased substantially (r = 0.85, P < 0.001,
      mean difference and standard deviation: 0.09 +/- 0.96 l.min-1). CONCLUSIONS: The
      results of this study indicate that weight is a very important factor in
      unreliable measurement of CO by impedance cardiography in cardiac surgery
      patients. The calculation equation as proposed by Sramek and Bernstein is not
      accurate enough in patients with more than 15% of weight deviation. Therefore,
      the use of impedance cardiography in these patients is of limited value until an
      accurate correction factor has been developed.

PMID- 9241330
TI  - Complement partially mediates acid aspiration-induced remote organ injury in the
      rat.
AB  - BACKGROUND: Acid aspiration into one lung is known to cause both a local as well
      as remote organ injury characterized by neutrophil sequestration and subsequent
      edema. This study investigated investigated the role of the complement cascade in
      the development of acid aspiration-induced local lung and remote organ injuries
      using K-76 COONa (K76), an anticomplement agent that inhibits the complement
      pathway at the C5 step, and its usefulness as a treatment drug. METHODS:
      Anesthetized rats underwent tracheostomy and insertion of a cannula. K76 was
      intraperitoneally administrated prior to or immediately after the instillation of
      0.1 ml of HCl (0.1N) or phosphate buffer solution (PBS) into the left lung.
      Inflammatory responses were evaluated by tumor necrosis factor alpha (TNF alpha)
      in the plasma and the bronchoalveolar lavage fluid (BALF) (n = 4), tissue
      myeloperoxidase (MPO), wet-to-dry weight ratio (W/D ratio) (n = 6), and protein
      concentration in the BALF (n = 6). RESULTS: Acid instillation caused an increase
      in the plasma TNF alpha, which was significantly attenuated by the administration
      of K76 prior to or after the acid instillation. Acid instillation to the left
      lung resulted in an increase of MPO and W/D ratios of the left lung, the right
      lung, and the small intestine. The administration of K76 inhibited the increase
      of MPO in these organs. K76 inhibited the increase of W/D ratios of the right non
      instillated lung and the small intestine. Acid instillation led to increased
      protein concentration in the BALF of the left lung, which was not inhibited by
      K76. K76 administrated after the acid instillation had the same effects. TNF
      alpha in the BALF was not detected in all groups. CONCLUSION: These results
      suggest that localized acid aspiration induces, through the C5a step of the
      complement system-dependent mechanisms, TNF alpha formation and neutrophil
      sequestration, which caused the increase of endothelial permeability of the
      systemic organs. K76 is effective as a treatment drug in modulating some of the
      injuries caused by the acid instillation, but further investigations is warranted
      as to its potential as a therapeutic agent.

PMID- 9241331
TI  - Central cardiovascular and oxygen variables during haemorrhage in the pig.
AB  - BACKGROUND: We evaluated the ability of the standards issued by the Danish
      Society of Anaesthesiologists to reflect a blood loss. METHODS: In 9 pigs bled (0
      24 ml kg-1 and retransfused (to 28 ml kg-1) during halothane anaesthesia central
      cardiovascular, thoracic electrical impedance (TI), oxygen, acid-base and
      temperature variables were recorded. RESULTS: With the recommendation for minor
      surgery (mean arterial pressure (MAP) and heart rate (HR)), the correlation to
      the blood loss was 0.74 (P < 0.001) and with that for major surgery (MAP, HR,
      central venous pressure (CVP) and rectal temperature (Tempr)) it was 0.79 (P <
      0.001). With the recommendation for extensive surgery (MAP, HR, CVP, pulmonary
      artery catheter variables and the central-peripheral temperature difference
      (delta Tempr-t)), the correlation was 0.84 (P < 0.001). Non-invasive monitoring
      (MAP, HR, delta Tempr-t, TI and near-infrared spectroscopy of the brain
      (SinvosO2)) was only slightly better than basal monitoring (r = 0.76, P < 0.001).
      However, adding arterial base excess (BE), TI, and peripheral temperature (Tempt)
      to the recommendation for major surgery resulted in a correlation of 0.87 (P <
      0.001), while adding BE and TI to the recommendation for extensive surgery raised
      correlation to only 0.88 (P < 0.001). CONCLUSION: When the recommendations were
      followed the correlation to the blood loss ranged from 0.74-0.84. However, with
      the recording of MAP, HR, CVP, delta Tempr-t, BE and TI a correlation of 0.87 was
      achieved, indicating that a pulmonary artery catheter may not be in need for
      patients undergoing surgical procedures with expected haemorrhage.

PMID- 9241332
TI  - Serum soluble selectins in patients undergoing cardiopulmonary bypass.
      Relationship with circulating blood cells and inflammation-related cytokines.
AB  - BACKGROUND: Membrane-bound selectins mediate the adhesion among leukocytes,
      platelets and endothelial cells, while circulating (soluble) selectins may
      function as competitive inhibitors of them. Open heart surgery is known to induce
      activation of these cells. METHODS: We studied the acute responses of soluble
      selectins, circulating blood cells and inflammation-related cytokines in 12
      patients undergoing elective open heart surgery with cardiopulmonary bypass.
      Serial blood samples were withdrawn before, during and after surgery. RESULTS:
      Serum soluble E-selectin concentrations did not change significantly during all
      the perioperative period. In contrast, P-selectin decreased after the initiation
      of cardiopulmonary bypass and remained low until the end of surgery. L-selectin
      showed a similar course. A decrease in platelet count and albumin was found
      during the perioperative period and an increase in leukocyte count was found
      after cardiopulmonary bypass. Clear elevations in circulating IL (Interleukin)-6,
      IL-8, and IL-10 were found after the end of surgery, while IL-12 levels remained
      undetectable. CONCLUSIONS: While serum inflammatory cytokines clearly rise in
      response to open heart surgery, soluble selectins do not change (E) or decrease
      (P and L). Correcting for haemodilution, E-selectin rises postoperatively, but
      the decrease in P- and L-selectins is not explained by haemodilution.

PMID- 9241333
TI  - Results of in vitro contracture tests for the diagnosis of malignant hyperthermia
      susceptibility in monozygote twins.
AB  - BACKGROUND: Malignant hyperthermia susceptibility is a pharmacogenetic disorder
      in which susceptible individuals may develop a potentially life-threatening
      hypermetabolism when exposed to certain anaesthetic agents. The most common
      diagnostic method is the in vitro contracture test (IVCT) of skeletal muscle
      biopsies. There is a wide variation in the size of contractures between
      susceptible individuals and the reproducibility of the test in humans has not
      been evaluated. METHODS: We have performed the IVCT in 4 monozygote pairs of
      twins, which gave us on opportunity to study the reproducibility. RESULTS: The
      clinical diagnoses were consistent in all twin pairs, although slight differences
      in contractures and thresholds were seen. CONCLUSION: In this material the
      reproducibility of the IVCT was found to be satisfactory.

PMID- 9241334
TI  - Comparison of body temperature changes during laparoscopic and open
      cholecystectomy.
AB  - BACKGROUND: Prevention of hypothermia during abdominal surgery by insulating or
      heat-transferring methods has been the subject of numerous investigations. This
      study approaches the problem from a less discussed point of view, i.e. the effect
      of different surgical techniques on body temperature changes. METHODS: Body
      temperature was measured at 3 core and 6 skin points in 40 patients scheduled for
      cholecystectomy through open laparotomy or laparoscopy with pneumoperitoneum
      created and maintained with unwarmed carbon dioxide (CO2) insufflation. End-tidal
      CO2 was kept constant by adjustments of respiratory frequency. Anaesthesia,
      intravenous infusions, and draping of the patients were standardized. RESULTS:
      During the first 1 h of anaesthesia core temperatures decreased approximately by
      0.7 degrees C and distal skin temperatures increased by 7 degrees C in both
      groups. At the end of surgery heat balance was similar in both groups. An
      increase of 2.5 1.min-1 in respiratory minute volume was needed to control end
      tidal CO2 levels in the laparoscopy group during pneumoperitoneum which was
      maintained with a CO2 flow of 1.2 1.min-1 through the abdominal cavity.
      CONCLUSION: Laparoscopic technique with unwarmed carbon dioxide insufflation does
      not offer any advantage in terms of body temperature changes when compared to
      open surgery.

PMID- 9241335
TI  - Evaluation of residual neuromuscular blockade using modified double burst
      stimulation.
AB  - BACKGROUND: To assess the degree of residual neuromuscular blockade, double burst
      stimulation (DBS) is commonly applied in the clinical setting. However, fades in
      response to DBS3,3 can rarely be identified manually when train-of-four (TOF)
      ratios are > or = 0.70, and, in contrast, fades in response to DBS3,2 are felt
      manually in an undesirably high proportion of cases, even at TOF ratios greater
      than 0.7. We investigated whether a new monitoring method, modified DBS, would be
      useful to determine an adequate degree of recovery from neuromuscular blockade.
      For modified DBS, two burst stimuli were applied at an interval of 750 ms. The
      first stimulation in the modified DBS consisted of two stimuli of 0.3 ms duration
      at 50 Hz and the second of two stimuli of 0.2 ms duration at 50 Hz. METHODS:
      Forty-five adult patients undergoing elective nitrous oxide-oxygen-isoflurane
      anesthesia were randomly divided into one of three groups: DBS3,3 group (n = 15),
      DBS3,2 group (n = 15), or modified DBS group (n = 15). During recovery from
      vecuronium-induced neuromuscular blockade, on both forearms, DBS3,3, DBS3,2, and
      modified DBS were delivered in the DBS3,3 group, DBS3,2 group, and modified DBS
      group, respectively. One hand and forearm (fixed arm) were immobilized to
      quantify the degree of neuromuscular blockade mechanically, and the contralateral
      arm (free arm) was unrestrained. An observer determined tactiley on the free arm
      the presence or absence of fade in response to the three DBS patterns. RESULTS:
      Probabilities of detection of fade in response to the DBS3,3 were 67% (TOF ratio
      of 0.51-0.60), 40% (0.61-0.70), 19% (0.71-0.80), 5% (0.81-0.90), and 0% (0.91
      1.00). Those to the DBS3,2 were 95% (0.51-0.60), 93% (0.61-0.70), 83% (0.71
      0.80), 65% (0.81-0.90), and 38% (0.91-1.00). Those to modified DBS were 90% (0.51
      0.60), 86% (0.61-0.70), 65% (0.71-0.80), 25% (0.81-0.90), and 3% (0.91-1.00).
      Those modified DBS was more sensitive in diagnosing residual neuromuscular
      blockade than DBS3,3 at the TOF ratio of 0.51-0.90, but was less sensitive than
      DBS3,2 at the TOF ratio of 0.81-1.00 (P < 0.05). CONCLUSION: Our results indicate
      that the modified DBS may be a useful stimulation pattern to diagnose the
      adequacy of recovery from neuromuscular blockade.

PMID- 9241336
TI  - Granisetron reduces incidence of nausea and vomiting after breast surgery.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) remains a troublesome
      problem. The study was performed to evaluate the antiemetic efficacy of
      prophylactic granisetron, a selective 5-hydroxytryptamine type 3 receptor
      antagonist, on the incidence of PONV in patients undergoing general anaesthesia
      for breast surgery. METHODS: In a randomized, placebo-controlled, double-blind
      study, 50 female patients, 45-68 years, were given a single dose of either
      placebo (saline, n = 25) or granisetron (40 micrograms.kg-1, n = 25)
      intravenously over 2-5 min immediately before the induction of anaesthesia.
      Postoperatively, during the first 24 hours after anaesthesia, the incidence of
      PONV and adverse events was recorded. RESULTS: The treatment groups were similar
      for patient demographics, types of surgery, anaesthetic and postoperative
      management. Postoperatively, the incidence of PONV was 48% and 16% after
      administration of placebo and granisetron, respectively (P < 0.05). No
      differences in the incidence of other adverse events were observed between the
      two groups. CONCLUSION: Granisetron is an effective antiemetic for preventing
      PONV in patients undergoing general anaesthesia for breast surgery.

PMID- 9241337
TI  - Serum potassium concentrations after suxamethonium in patients with familial
      amyloid polyneuropathy type I.
AB  - BACKGROUND: Suxamethonium produces an abnormal increase in serum potassium in
      some neurological diseases and some authors have suggested that it is safer not
      to use this drug in patients with familial amyloid polyneuropathy (FAP). However,
      there are no data previously reported to support this hypothesis. The aim of this
      study was to evaluate the magnitude of the potassium increase produced by
      suxamethonium in FAP type I. METHOD: Twenty-one FAP Met 30 patients anaesthetised
      for liver transplantation were studied. Age was 34.9 +/- 6.9 years (mean +/- SD),
      time elapsed from first symptom 5.5 +/- 3.2 years and weight was 14 +/- 9% below
      ideal body weight. Anaesthesia was induced with thiopentone and low-dose
      fentanyl. Samples for blood gas and 5 min after 1 mg/kg of suxamethonium was
      given for tracheal intubation. RESULTS: Before induction serum potassium levels
      were 3.8 +/- 0.4 mmol/L. One minute after suxamethonium, values were 3.8 +/- 0.4
      mmol/L and 5 min after 4.3 +/- 0.5 mmol/L. The maximal increase observed was 1.6
      mmol/L (from 3.4 mmol/L to 5.0 mmol/L). CONCLUSION: The average increase in
      plasma potassium concentrations observed in FAP patients after suxamethonium was
      similar to the increase observed in a normal population by others. Our study can
      exclude the hypothesis that an anomalous increase in potassium would be a typical
      and frequent response to suxamethonium in FAP met 30 patients. However, we cannot
      exclude that a dangerous rise in serum potassium may exist in a certain
      percentage of FAP patients.

PMID- 9241338
TI  - The effect of halothane on mivacurium infusion requirements in adult surgical
      patients.
AB  - BACKGROUND: The extent of interaction between volatile anaesthetics and
      neuromuscular blocking agents depends both on the inhalational anaesthetic and
      the muscle relaxant. Halothane has the weakest potentiating effect on
      neuromuscular blocking drugs and previous studies of the interaction between
      halothane and mivacurium have been contradictory. We were interested in
      determining the effect of different levels of halothane-nitrous oxide anaesthesia
      on infusion requirements of mivacurium. METHODS: Sixty adult surgical patients
      were studied. Anaesthesia was induced with thiopentone and fentanyl and
      intubation facilitated with mivacurium 0.15 mg.kg-1. The patients were randomly
      assigned to one of four study groups. The control group received nitrous oxide in
      oxygen (2:1) supplemented with fentanyl, while in the other groups halothane was
      administered at different end-tidal concentrations: 0.19% (group 2), 0.37% (group
      3), 0.74% (Group 4), corresponding to 0.25, 0.5 and 1.0 MAC of halothane.
      Neuromuscular block was kept at 95% with a closed-loop feedback infusion of
      mivacurium and monitored with electromyography. Plasma cholinesterase
      concentrations and dibucaine numbers were determined. RESULTS: Mivacurium
      infusion requirements (mean +/- SD) were 7.5 +/- 3.1 micrograms.kg-1.min-1 with
      nitrous oxide-fentanyl anaesthesia. In the groups receiving 0.25, 0.5 or 1.0 MAC
      of halothane the steady-state infusion rates of mivacurium were reduced to 6.3 +/
      2.8, 5.6 +/- 1.4 and 5.7 +/- 2.5 micrograms.kg-1.min-1 (P < 0.05), respectively.
      There was a linear relationship between mivacurium infusion requirements and
      plasma cholinesterase activity. CONCLUSIONS: Halothane anaesthesia reduces
      mivacurium infusion requirements by 15-25% compared to nitrous oxide-fentanyl
      anaesthesia. Interindividual differences in the extent of this interaction are
      great.

PMID- 9241339
TI  - In vivo effects of halothane, enflurane, and isoflurane on hepatic sinusoidal
      microcirculation.
AB  - BACKGROUND: It has been proposed that halogenated anaesthetics interfere with the
      endothelium-dependent circulatory control by attenuating the effects of
      endothelium-derived relaxing factor (EDRF/NO). This study was designed to
      determine whether or not volatile anaesthetics in vivo influence the
      microvascular tone in hepatic sinusoids. METHODS: Using epifluorescence
      videomicroscopy, we compared the effects of the volatile anaesthetics halothane,
      enflurane, and isoflurane on hepatic microcirculation halothane, enflurane, and
      Animals were initially anaesthetized with pentobarbitone (50 mg.kg-1 i.p.) to
      allow instrumentation and laparotomy and were randomly allocated to one of 4
      groups (n = 5-6 each) to receive either a supplementary dose of i.v.
      pentobarbitone (25 mg.kg-1; control group) or 0.75 MAC halothane, enflurane or
      isoflurane (1.5 MAC.h). RESULTS: Halothane decreased significantly the volumetric
      blood flow as compared with isoflurane (P < 0.05) or pentobarbitone controls (P <
      0.05). The decrease in sinusoidal blood flow caused by halothane was largely
      attributable to a decrease in sinusoidal diameter (P < 0.05), while red blood
      cells velocity remained unchanged. Isoflurane led to a significant decrease in
      sinusoidal width compared with controls (P < 0.05) but an increase in red cell
      velocity offset the effect of sinusoidal narrowing of volumetric blood flow,
      while enflurane had no significant effect on any of the measured parameters.
      CONCLUSION: This study provides the first direct evidence that the volatile
      anaesthetics halothane and isoflurane in vivo shift the hepatic microvascular
      tone toward a more constricted state; however, flow velocity is enhanced with
      isoflurane, offsetting this effect. As a result the volumetric flow is at least
      affected by isoflurane, then enflurane and most significantly by halothane.
      Furthermore, our data are consistent with the concept that volatile anaesthetics
      in clinically relevant concentrations may influence the balance between
      endothelium-derived vasoactive factors which control microvascular tone.

PMID- 9241340
TI  - Lidocaine-induced hemodynamic effects are enhanced by the inhibition of
      endothelium-derived relaxing factor in dogs.
AB  - BACKGROUND: Lidocaine has been shown to have direct vasoconstrictive effects at
      low concentrations. Since lidocaine inhibits endothelium-dependent vasodilation
      in vitro, the vasoconstrictor effect of lidocaine may be due to inhibition of
      endothelium-derived relaxing factor(EDRF/NO). Therefore, the current study was
      designed to determine the effects of NG-nitro-L-arginine (L-NNA), a potent
      inhibitor of nitric oxide synthase, on systemic and pulmonary hemodynamics during
      lidocaine infusion. METHODS: Systemic and pulmonary hemodynamic effects of
      lidocaine infusion, 1 mg.kg-1.min-1, for 10 min were measured in dogs
      anesthetized with 1% halothane in oxygen. Dogs were studied twice with an
      interval of 1 week in a cross-over study, and were assigned to one of two groups
      that received saline or L-NNA intravenously in group 1 (n = 8), or L-NNA or L-NNA
      + L-arginine which reverses the nitric oxide synthesis inhibitor effect of L-NNA,
      intravenously in group 2 (n = 8) prior to lidocaine infusion. The free serum
      concentration of and protein-binding ratio for lidocaine were measured. RESULTS:
      With saline pretreatment in group 1, lidocaine infusion significantly decreased
      cardiac index (CI) and significantly increased mean pulmonary arterial pressure
      (MPAP), pulmonary arterial occlusion pressure (PAOP), systemic vascular
      resistance (SVR) and pulmonary vascular resistance (PVR). L-NNA pre-treatment in
      group 1 significantly enhanced the changes in CI, MPAP, PAOP, SVR and PVR during
      lidocaine infusion. In group 2, L-arginine infusion partially offset the additive
      effects of L-NNA to the depressive effects of lidocaine. There were no
      significant differences in free serum concentration of or protein-binding ratio
      for lidocaine among the groups. CONCLUSION: In contrast to in vitro study,
      vasoconstrictor effect of lidocaine is enhanced when a capacity for compensatory
      vasodilation including EDRF/NO pathway is exhausted in halothane-anesthetized
      dogs.

PMID- 9241342
TI  - Grading of severity of postdural puncture headache after 27-gauge Quincke and
      Whitacre needles.
AB  - BACKGROUND: Small-gauge needles are reported to have a low incidence of
      complications. Pencil-point needles are associated with a lower frequency of
      postdural puncture headache (PDPH), but a higher failure rate than Quincke
      needles. METHODS: The incidence of PDPH was investigated in 200 patients under
      the age of 45, undergoing day-care surgery, after spinal anaesthesia with either
      27-gauge Quincke or Whitacre needle. The severity of headache was graded as I
      (mild), II (moderate) or III (severe) using a grading system based on the visual
      analogue scale (VAS) associated with a functional rating (FG). RESULTS: The
      frequency of PDPH following the Whitacre needle was 0% and 5.6% after the Quincke
      needle (P = 0.05). Two PDPHs were assessed as grade III, and three as grade II.
      All PDPHs occurred when the Quincke needle bevel was withdrawn perpendicular to
      the dural fibres following parallel insertion. No PDPH occurred when the bevel
      was inserted and removed parallel to the dural fibres (P < 0.05). There was no
      statistical difference (P > 0.08) in the incidence of PDPH and postdural puncture
      related headaches (PDPR-H) in patients with recurrent headaches or migraine
      compared to patients with no previous history of headaches. CONCLUSIONS: We
      conclude that the 27-gauge Whitacre needle is the 'needle of choice' in patients
      with normal body stature. The incidence of PDPH following Quincke needles may not
      only be affected by the direction of the bevel during insertion but also during
      removal. Statistically, there was no gender variation in PDPH in this study (P =
      0.5). A previous history of recurrent headache or migraine does not predispose to
      PDPH.

PMID- 9241341
TI  - 2-Chloroprocaine antagonism of epidural morphine analgesia.
AB  - BACKGROUND: 2-Chloroprocaine (2-CP) used for lumbar epidural anesthesia (LEA)
      reportedly decreases the efficacy of epidural morphine (EM) administered for post
      cesarean section (CS) analgesia. The amount of supplemental i.v. morphine self
      administered by the patient via the patient-controlled analgesia device (PCA) is
      used to study the interaction between EM and 2-CP. METHODS: Forty-two patients
      scheduled for elective CS were randomly divided into 3 equal groups, and received
      2-CP, 2-CP + epinephrine (Epi, 5 micrograms.ml-1) or 2% lidocaine (Lido) with Epi
      for LEA. All patients received 5 mg EM and i.v. PCA morphine for postoperative
      pain. Cumulative amount of i.v. morphine used in the first 24 hours as well as
      the amount of the drug used during each 2-h period were noted. Nonparametric
      analysis of variance and Chi-squared analysis were used for statistical
      comparisons. RESULTS: The mean cumulative 24-h i.v. PCA morphine requirement in
      the 2-CP, 2-CP+Epi and Lido+Epi groups respectively was 20.5 +/- 24, 33.1.5 +/-
      27 and 4.07 +/- (mean +/- SD). The Lido + Epi group used significantly less
      morphine (P = 0.01) compared to either of the 2-CP groups with no significant
      difference between the 2-CP groups. The maximum i.v. PCA morphine use occurred in
      the first 4 hours following surgery in all three groups. CONCLUSION: Analgesic
      efficacy of EM is decreased when 2-CP is used for LEA compared to when Lido + Epi
      is used.

PMID- 9241343
TI  - Time course of subjective pain ratings, and wound and leg tenderness after
      hysterectomy.
AB  - BACKGROUND: Little information is available on time course of wound tenderness
      and relationship to subjective pain ratings following surgery. Furthermore, it is
      not clarified whether surgical procedures may induce hyperalgesia to mechanical
      stimulation outside the area of the surgical incision. We have therefore assessed
      postoperative pain and pressure pain thresholds (PPT) adjacent to and remote from
      the surgical incision in 16 patients undergoing hysterectomy. METHODS: Pressure
      pain threshold was assessed with pressure algometry preoperatively, 4 and 6 and
      1, 4 and 8 d after surgery on the abdominal wall 0.05, 5, 10 and 15 cm
      perpendicular to the wound, and on the anterior surface of the left thigh and
      tuberositas tibia. Furthermore, pain was assessed on a visual analogue scale
      (VAS) at rest and during cough. RESULTS: PPT decreased significantly 0.5, 5, 10
      and 15 cm from skin incision up to 96 h after surgery (P < 0.01) with a trend
      towards higher PPT with increasing distance from the wound. There was no
      significant changes in PPT on the thigh or the tuberositas tibia (P = 0.49 and P
      = 0.12) and no correlation between changes in PPT near the wound and in remote
      (areas the legs) (Rs = -0.082, P = 0.53, respectively). VAS at rest increased
      from 4 to 24 h and the cough values, remained elevated throughout the study (P <
      0.05). An inverse relationship was observed between PPT 5 cm from the incision
      and VAS at rest (Rs = -0.406, P = 0.0002) and during cough (Rs = -0.398, P =
      0.0002). CONCLUSION: These results indicate that wound pressure algometry
      correlates to postoperative pain at rest and during movement and may be an
      alternative way of assessing wound pain and tenderness. Increased tenderness to
      mechanical stimulation remote from the surgical wound could not be demonstrated.

PMID- 9241344
TI  - Emergency spinal anaesthesia in the prone position.

PMID- 9241345
TI  - Subcutaneous emphysema and pneumothorax during laparoscopy for ectopic pregnancy
      removal.
AB  - We report a case of subcutaneous emphysema and pneumothorax during laparoscopic
      removal of ectopic pregnancy. Increases in airway pressures and end-tidal carbon
      dioxide, simultaneously with decrease of lung compliance, led quickly to
      diagnosis of pneumothorax. We recommend a careful monitoring of these variables
      during laparoscopic procedures. Carbon dioxide pneumothorax can occur even
      without pulmonary or pleural trauma.

PMID- 9241346
TI  - Nasal turbinate dislocation caused by nasotracheal intubation.
AB  - A case of nasal turbinate dislocation secondary to nasotracheal intubation is
      presented. Although mild epistaxis had occurred in the days following extubation,
      the complication was not recognized until after the patient presented with
      headache and impairment of nasal breathing 6 months later. Endoscopy revealed the
      dislocation of the middle turbinate into the nasopharynx. Treatment by resection
      of the dislodged turbinate resulted in relief of symptoms. Physicians should be
      aware of the possibility of severe nasal damage following even apparently
      uncomplicated intubation and obtain consultation by an otorhinolaryngologist
      after epistaxis or obstructed nasal breathing.

PMID- 9241347
TI  - New preoperative fasting guidelines in Norway.

PMID- 9241348
TI  - Simultaneous record of epidural and intracranial pressure.

PMID- 9241349
TI  - Nodulation genes in the Rhizobium--plant signal exchange.
AB  - The process of the host-plant recognition by rhizobia is complex and multi-step.
      The interaction between legumes and microorganisms results in the induction of
      the root nodule. This symbiotic interaction is highly host-specific. Bacteria
      within nodules fix atmospheric nitrogen. This process is of immense ecological
      and economic significance. The subject of this presentation is the molecular
      mechanism by which the bacterium determines its host-specific characteristics.
      First flavonoids secreted by the plant roots induce the transcription of
      bacterial genes involved in nodulation, the so-called nod genes. This leads to
      the next step of the signalling system, i.e. the production and secretion of lipo
      oligosaccharide molecules by rhizobia. These signal molecules have various
      discernible effects on the roots of the host leguminous plants. The bacterial
      nodulation factors were isolated and structurally identified as substituted and N
      acylated chitin oligosaccharides. These prokaryotic signals play a key role in
      the symbiosis by controlling the host specificity of the bacteria. They
      constitute a new class of signalling molecules able to elicit nodule
      organogenesis in leguminous plants in the absence of bacteria. More recent
      studies implicate involvement of root cell membrane depolarization and ion
      selective channels in the communication processes that initiate nodule formation.

PMID- 9241350
TI  - Nuclear extrachromosomal DNA of higher plants.
AB  - Recent reports indicate that minichromosomes and other small genetic entities may
      occur in the nuclei of uninfected higher plants. They become especially abundant
      under some special growth conditions and, sometimes, resemble extrachromosomal
      genes of ciliated protozoa. An example of such gene-sized DNA species was
      isolated from resting wheat embryos. The presence of telomeric sequences at its
      termini and the ability to replicate autonomously in wheat nuclei made it
      possible to distinguish this nuclear minichromosome from chromosomal DNA
      fragmentation products. The biological significance of plant minichromosomes
      remains to be elucidated.

PMID- 9241351
TI  - Galactolipase and chilling sensitivity of plants.
AB  - Galactolipase is a lipid acyl hydrolase (EC 3.1.1.26) acting predominantly on
      galactolipids which constitute up to 80% of total acyl lipids in chloroplast
      membrane. Evidence is presented on the involvement of this enzyme in plant
      response to chilling via degradation of membrane lipids and the increase of free
      fatty acids, associated with reduced oxygen evolution in the Hill reaction. The
      occurrence of two pools of fatty acids has been hypothesized. Analysis of
      numerous plant species showed higher galactolipase activity in the chilling
      sensitive than in the chilling-resistant plants. Differences in the pH-dependence
      curve and in the response to detergents of galactolipases from these two groups
      of plants suggest heterogeneity of the enzyme. Referring to the hypothesis
      concerning the role of high melting-point fatty acids of phosphatidylglicerol
      molecular species in chilling sensitivity the data are presented against
      generalization of this hypothesis.

PMID- 9241352
TI  - Isolation and classification of a family of cyclin gene homologues in Lupinus
      luteus.
AB  - The lupine (Lupinus luteus cv. Ventus) cDNA clones encoding homologues of cyclin
      (CycB1;2, CycB1;3, CycB1;4) have been isolated from cDNA library prepared from
      roots inoculated with Bradyrhizobium lupini. Comparison of the deduced amino-acid
      sequences of CycB1;2, CycB1;3, CycB1;4 and previously described CycB1;1 (Deckert
      et al. 1996, Biochimie 78, 90-94) showed that they share 46-65% of identical
      amino acids. The presence of conserved residues (Renaudin et. al., in The Plant
      Cell Cycle, in the press; Renaudin et al., Plant Mol. Biol, in the press) along
      with phylogenetic analysis of known plant cyclins revealed that the four lupine
      sequences belong to subgroup 1 of B-like mitotic cyclins.

PMID- 9241353
TI  - UDP-glucose:solasodine glucosyltransferase from eggplant (Solanum melongena L.)
      leaves: partial purification and characterization.
AB  - Uridine 5'-diphosphoglucose-dependent glucosyltransferase which catalyzes the
      glycosylation of solasodine i.e. UDP-glucose:solasodine glucosyltransferase, is
      present in leaves, roots, unripe fruits and unripe seeds of eggplant (Solanum
      melongena L.). The glucosylation product is chromatographically identical with
      authentic solasodine 3 beta-D-monoglucoside, a putative intermediate in the
      biosynthesis of solasodine-based glycoalkaloids characteristic of the eggplant.
      The enzyme was purified about 50-fold from crude cytosol fraction of eggplant
      leaves by ammonium sulphate precipitation and column chromatography on Q
      Sepharose and Sephadex G-100. The native enzyme has a molecular mass of approx.
      55 kDa and pH optimum of 8.5. Divalent metal ions are not required for its
      activity but the presence of free-SH groups is essential. Besides solasodine (Km
      = 0.04 microM), the enzyme effectively glucosylates tomatidine, another steroidal
      alkaloid of the spirosolane type, but it is virtually inactive towards the
      solanidane-type steroidal alkaloids such as solanidine or demissidine. The enzyme
      is specific for UDP-glucose (Km = 2.1 microM) since unlabelled ADP-, GDP-, CDP-
      or TDP-glucose could not effectively compete with UDP-[14C]glucose used as the
      sugar donor for solasodine glucosylation. Moreover, no synthesis of labelled
      solasodine galactoside was observed when UDP-[14C]glucose was replaced with UDP
      [14C]galactose.

PMID- 9241354
TI  - Reversibility of the oleanolic acid monoglycosides transport across the tonoplast
      in vacuoles isolated from Calendula officinalis leaves.
AB  - The possibility of the reversible tonoplast transport of oleanolic acid
      monoglycosides was investigated in vacuoles isolated from Calendula officinalis
      leaf protoplasts. The obtained results point to the reversibility of the
      transport of monoglucoside I, whereas monoglucuronide F seems to be definitely
      stored in the vacuolar space.

PMID- 9241355
TI  - Purification and some properties of a novel dsRNA degrading nuclease bound to rye
      germ ribosomes.
AB  - A two-step procedure including affinity chromatography for purification of rye
      germ ribosomal nuclease that degrades double-stranded RNA from a virus of
      Penicillium chrysogenum and the poly(I).poly(C) complex was developed. The
      specific activity towards poly(I).poly(C) of the obtained nuclease preparations
      was 30 times as high as that of ribosomes. The recovery of activity was 3.4% when
      the Octyl-Sepharose column was used, and 2.0% in the case of the Phenyl-Sepharose
      column. On polyacrylamide/SDS gel electrophoresis the nuclease was resolved into
      two proteins of molecular mass 62 kDa and 57 kDa, respectively. 2-Mercaptoehanol
      and Mn2+ stimulated the activity of the purified enzyme. Glycerol (20%-50%
      concentration) stabilized enzyme. In addition to activity towards dsRNA and ssRNA
      the enzyme cleaves native and denatured DNA. It is suggested that this type of a
      nuclease takes part in regulation of the mRNA level in cytoplasm.

PMID- 9241356
TI  - Studies on the translation mechanism of subgenomic RNA of potato leafroll virus.
AB  - The expression of open reading frames located on the subgenomic RNA (sgRNA) has
      been studied in an in vitro transcription and translation system. The obtained
      results indicate: a) translation of sgRNA occurs according to the scanning model
      since the insertion of palindrome (delta G0 = -61 kcal/mol) prevents the
      initiation of translation; b) ORF6 is translated by suppression of the stop codon
      separating ORF4 from ORF6 and the presence of suppressor tRNA is necessary for
      the readthrough; c) the presence of leader sequence of sgRNA (212 nucleotides)
      decreases the translation efficiency of ORFs located downstream and it affects
      the ratio of products of ORF4 and ORF5; d) 3'UTR does not influence on an
      expression of genes located on the sgRNA.

PMID- 9241357
TI  - Autonomous replication of a wheat DNA sequence in isolated wheat nuclei.
AB  - A fragment of wheat nuclear DNA was shown to be able to replicate autonomously in
      wheat nuclei. The fragment was 637-bp long and contained telomeric repeats at
      both termini. Its replication was manifested by the appearance of a radioactive
      reaction product of the same approximate size. Further analyses showed that the
      linear, double-stranded reaction product was labelled along its entire length and
      contained the same number of similarly located HaeIII sites as did the fragment
      tested. Prokaryotic DNA remained unlabelled under the same assay conditions.

PMID- 9241358
TI  - The influence of polyamines on polymerase chain reaction (PCR).
AB  - Twelve different polyamines from three functional groups have been tested for
      their influence on polymerase chain reaction (PCR). Using crude total DNA from
      liverwort Pellia borealis we have found that tri- and tetramines can strongly
      improve the efficiency of PCR.

PMID- 9241359
TI  - The enthalpimetric determination of inhibition constants for the inhibition of
      urease by acetohydroxamic acid.
AB  - The effect of concentration of acetohydroxamic acid (AHA) on inhibition of jack
      bean urease in phosphate buffer, pH 7.0, at 25 degrees C, was studied. The
      measurements were performed at urease concentration of 2.5 mg/100 cm3 for
      concentrations of urea and AHA ranging in the range of 2-50 mmol dm-3 and 0.25-10
      mmol dm-3, respectively. The reactions were monitored by two techniques:
      analytical and enthalpimetric. For the analytical technique the growth of ammonia
      concentration in the course of the reaction was determined. From the recorded
      progress curves the following parameters were calculated for each inhibitor
      concentration: the initial reaction rate, the steady-state rate and the inversion
      constant. From these parameters the inhibition constants of the initial and
      steady-state stages of the reaction, Ki and Ki, were calculated. The former
      constant did not change whereas the latter one proved to decrease quickly with an
      increase in inhibitor concentration. This behaviour resulted from the fact that
      the inactive complex EI was not a product of internal inversion but was formed in
      the reaction: 2/3I + EI-->(EI.2/3I). The dissociation constant of this complex is
      equal to about 0.3 x 10(-3) (mol dm-3)2/3.

PMID- 9241360
TI  - Changes in red blood cell membrane structure in patients with chronic renal
      failure.
AB  - The properties of red blood cell membranes in patients with chronic renal failure
      were investigated using electron paramagnetic resonance spectroscopy. Using spin
      traps, 5,5-dimethylpirroline-1 oxide and N-tert-butyl-alpha-phenylnitrone, we
      found generation of hydroxyl radicals in the blood of patients with chronic renal
      failure after 20 min of regular hemodialysis. The physical state of membrane
      proteins and membrane osmotic fragility and reductive properties of red blood
      cells were studied. The increase in the relative correlation time of 4-(2
      iodoacetamido)-2,2,6,6-tetramethylpiperidine-1 oxyl indicates the immobilization
      of membrane protein molecules in erythrocytes of chronic renal failure patients.
      The decrease in membrane protein mobility was observed in whole blood incubated
      with tert-butylhydroperoxide, regardless of the presence of iron. We found that
      the addition of ferrous ions did not aggravate profound changes in membrane
      proteins induced with tert-butylhydroperoxide. We also demonstrated higher
      osmotic fragility of erythrocytes in the patients with renal failure as compared
      to normal subjects. These alterations in membrane structure of red blood cells in
      hemodialysed patients suggest that hydroxyl radicals generated during
      hemodialysis can play an important role in the oxidative mechanism of erythrocyte
      damage.

PMID- 9241361
TI  - Activity of cancer procoagulant (CP) in serum of patients with cancer of lung,
      breast, oesophagus and colorectum.
AB  - Activity of cancer procoagulant (CP) was studied in blood serum of 90 patients
      with cancer of lung, breast, oesophagus and colorectum, and of 15 healthy people.
      The activity of CP was determined by the coagulation method. Sera of patients
      with cancer showed higher mean activity of CP than sera of healthy control. Of
      the 90 cancer patients 78 were identified correctly by this test as having cancer
      (sensitivity 85%). In the case of lung and colorectal cancers the higher CP
      activity was observed the more advanced was the clinical stage of cancer, and the
      test was positive in 100%. After radical removal of malignant tumor of lung,
      decreased CP activity was found.

PMID- 9241362
TI  - The activities and subcellular localization of cathepsin B and cysteine
      proteinase inhibitors in human ovarian carcinoma.
AB  - Ovarian carcinomas exhibited a higher cathepsin B activity than did normal
      ovaries. The plasma membrane fractions of ovarian cancers were enriched in the
      activities of both cathepsin and cysteine proteinase inhibitors. The ratio of
      cathepsin to the inhibitors in these fractions was higher at stage IV than at
      stage III of the disease, classified according to the Federation of International
      Gynecology and Obstetrics.

PMID- 9241363
TI  - The application of a flow cytometric assay for evaluation of phagocytosis of
      neutrophils.
AB  - Phagocytosis and the release of oxidative products generated by the respiratory
      burst have been studied in vitro under the influence of non-steroidal anti
      inflammatory drugs: naproxen and ibuprofen, using phagocytes of peripheral blood
      from healthy human donors. Phagocytosis was monitored by flow cytometry in order
      to investigate the uptake of propidium iodide-labelled bacteria (Staphylococcus
      aureus) by polymorphonuclear leucocytes. In addition, the phagocytic capacity and
      percentage of killed bacteria was measured in isolated neutrophils using the
      Pantazis & Kniker method. It was found that naproxen and ibuprofen affect the
      phagocytic function and hydrogen peroxide production in the examined
      granulocytes. These methods might be useful in investigations on neutrophil
      functions.

PMID- 9241364
TI  - Silybin and silydianin diminish the oxidative metabolism of human
      polymorphonuclear neutrophils.

PMID- 9241365
TI  - Changes in ATP level and iron-induced ultra-weak photon emission in bull
      spermatozoa, caused by membrane peroxidation during thermal stress.
AB  - ATP level, cell motility and viability, oxygen uptake, pyruvate kinase activity,
      and ultra-weak photon emission (UPE) induced by red-ox Fe(2+)-ascorbate cycling
      system were studied in fresh, in previously equilibrated in a glycerol diluent,
      and in cryopreserved bull spermatozoa, exposed to thermal stress by incubation of
      the cells at 44 degrees C. A sharp drop in motility and viability of fresh
      spermatozoa and even more so, of equilibrated and cryopreserved cells was
      accompanied by accumulation of ATP. When cell movement was totally inhibited, ATP
      utilization was decreased, while chemical energy continued to be produced by cell
      pyruvate kinase, one of the key glycolytic enzymes, which in spermatozoa is very
      active (6500 IU/g protein) and insensitive to feed-back inhibition by excess of
      ATP and L-cysteine. Accumulation of ATP during incubation at 44 degrees C in 0.9%
      NaCl was accompanied by rapid decrease in oxygen consumption by fresh spermatozoa
      and an increase in Fe(2+)-ascorbate induced UPE, followed by a sharp decrease in
      ATP level observed at the end of induced UPE measurement. The increase in photon
      emission due to lipid peroxidation was highly correlated with the increase in
      cell ATP level caused by thermal stress.

PMID- 9241366
TI  - Liver and serum antioxidant status after methanol intoxication in rats.
AB  - Activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH
      Px) and glutathione reductase (GSSG-R) and concentration of ascorbate, alpha
      tocopherol, non-protein and protein-bound sulfhydryl compounds and thiobarbituric
      acid-reactive substances (TBA-rs) were measured in liver and serum of rats 6, 12
      and 24 h and 2, 5 and 7 days after intoxication with 1.5 g or 3.0 g methanol/kg
      b.w. Liver GSH-Px and GSSG-R activities and SH-groups and ascorbate content were
      significantly diminished at 6 and 24 h, while TBA-rs were increased. Serum SOD,
      GSH-Px and GSSG-R activities and SH-groups concentration were reduced while TBA
      rs were elevated. The changes were more intensive after application of the higher
      dose of methanol. It is concluded that methanol impairs the liver and blood serum
      antioxidant mechanisms in rats.

PMID- 9241367
TI  - Identification of a microsatellite region composed of a long
      homopurine/homopyrimidine tract surrounded by AT-rich sequences upstream of the
      rat stress-inducible hsp 70.1 gene.
AB  - A DNA region containing several repetitive motifs has been detected about 1.9 kbp
      upstream of the transcription unit of the rat stress-inducible hsp 70.1 gene. The
      most interesting element of this area is a microsatellite sequence (GA)6CAG(TC)24
      that consists of an inverted repeat partially overlapping with the long
      homopurine/homopyrimidine tract (Pu/Py). DNA molecule within the described
      sequence can theoretically adopt alternate, non-B structures (H-DNA or cruciform)
      containing single-stranded regions. This microsatellite region is flanked by AT
      rich sequences containing several poly(A) tracts. The longest of them with a
      possible potential to destabilized a double-stranded DNA helix is localized
      around 160 bp downstream the (GA)6CAG(TC)24. The DNA fragment containing
      sequences described above was subcloned into the pUC19 vector and the resulting
      plasmid was subjected to the standard S1 susceptibility assay. Preliminary
      mapping of the S1 cleavage site indicates for the formation of the non-B-DNA
      structure within the Pu/Py tract. This is to our knowledge a first report on the
      existence of a complex microsatellite region on upstream the 5'-end of the hsp 70
      gene in mammals.

PMID- 9241368
TI  - Characterization of the Escherichia coli gene encoding a new member of the short
      chain dehydrogenase/reductase (SDR) family.
AB  - The nucleotide sequence of a chromosomal DNA fragment located upstream from the
      cysPTWAM operon of Escherichia coli was established. Sequence analysis indicates
      the presence of an open reading frame which has been designated ucpA (upstream
      cys P). The potential protein products exhibits strong sequence homology to the
      members of a large protein family, short-chain dehydrogenases/reductases.
      Involvement of Crp, FruR and IHF in the regulation of ucpA transcription in vivo
      was demonstrated.

PMID- 9241370
TI  - Quality of life in head and neck cancer patients.
AB  - In recent years the number of Quality of Life (QOL) studies has increased
      rapidly. When evaluating outcomes of clinical trials in patients, one should take
      into consideration QOL aspects in addition to the well-known standard biomedical
      endpoints. The difficult question is how to select the best instrument from the
      flood of papers. A review and a few reflections are presented.

PMID- 9241369
TI  - New cytostatic agents for the treatment of head and neck cancer.
AB  - Chemotherapy plays a definite role in the management of head and neck cancers,
      especially in combination with radiotherapy in patients with possibly curable
      disease. As far as new agents are concerned, the combinations of paclitaxel or
      docetaxel and gemcitabine with cisplatin or carboplatin deserve special
      attention. These regimens should be compared to the more classical combinations
      of cisplatin with Sefluorouracil or Ifosfamide in phase III trials. A special
      emphasis should be placed on the evaluation of these new agents in combination
      with radiotherapy, since all have strong radiopotentiating properties.

PMID- 9241371
TI  - ENT manifestations of relapsing polychondritis.
AB  - Relapsing polychondritis is a rare disease probably of auto-immune etiology
      comprising inflammatory involvement of cartilage as well as phenomena of
      vasculitis. ENT manifestations are frequent and the authors present a case
      involving chondritis of the auricle, the nasal septum and affecting the cochleo
      vestibular system as well. The diagnosis is based on the evocative clinical
      picture and on histological confirmation. Treatment consists of corticosteroids
      and immunosuppressive agents.

PMID- 9241372
TI  - External rhinoplasty approach for septal perforation.
AB  - The external rhinoplasty approach was used in nine patients for closure of septal
      perforations varying from 8 to 30 mm in diameter. Nasal obstruction was the most
      prominent symptom. An autologous graft was always inserted between the
      mucoperichondrial flaps. Seven perforations were closed successfully. Symptomatic
      improvement was achieved in all patients. The closure of nasal septal
      perforations via external rhinoplasty approach has a high percentage of success
      due to excellent exposure of the septum.

PMID- 9241373
TI  - Effects of adenoidectomy on sinusitis.
AB  - Effect of adenoidectomy on sinusitis was investigated in 78 children (aged 5 to
      7) with adenoid vegetation, sinusitis and otitis media with effusion. After a 6
      month period, improvement of the sinusitis was observed in 25 of the 45 children
      (56%) in the adenoidectomized group, and only in 8 of the 33 children (24%) in
      the non-adenoidectomized group. This was statistically significant in the
      adenoidectomized group (mean 2 = 7.65, p < .01). Through nasopharyngeal endoscopy
      in the adenoidectomized children in the 6 months following surgery, we noted
      decreased evidence of infection and/or inflammation. These findings may indicate
      that adenoidectomy is effective for sinusitis in children.

PMID- 9241374
TI  - The hummer, shaver or microdebrider.
AB  - The major goal in functional endoscopic sinus surgery (F.E.S.S.) is the precise
      and delicate removal of diseased tissue in order to prevent trauma to healthy
      mucosa, bleeding and scar formation. One of the advantages in this field is the
      use of the microdebrider. The authors describe the use of this instrument, as
      well as their own experience for nasal polypectomy, prior to the F.E.S.S.
      procedure.

PMID- 9241375
TI  - Non-Hodgkin's lymphoma of the paranasal sinuses. Report of two cases.
AB  - Lymphoma of the paranasal sinuses is relatively rare compared to the occurrence
      of carcinoma in the same region. The diagnosis is often missed at the early
      stages of the disease. Two cases of primary extranodal lymphoma of the maxillary
      sinus are reported. The diagnosis of these malignancies is emphasized.

PMID- 9241376
TI  - Electromyographic evaluation of vocal cord disorders.
AB  - In order to perform its basic functions, those of coordination of breathing,
      swallowing and speech, the larynx requires an intact neural apparatus to permit
      the perfect, well-coordinated action of the neuromuscular structures of extra-
      and intralaryngeal muscles. Electrophysiological measurements including
      electromyography, reflexmyography, electric and magnetic stimulated myography of
      the central motor nerve functions are the methods of classification of
      dysfunctions into neurapraxia, axonotmesis, neurotmesis, regeneration or
      myopathy. Different types of electrodes, depending on the methods of application,
      show a variety of neurophysiological findings which allow the investigator to
      decide about the type of lesion. An overview on neurophysiological techniques in
      vocal cord disorders is presented.

PMID- 9241377
TI  - The ageing voice: changes in fundamental frequency, waveform stability and
      spectrum.
AB  - In the present study we searched for age dependent acoustic changes in the voice
      of 205 men and women divided in four age groups from 60 to 99 years old. Sixty
      young men and women served as a comparison group. The findings cover three
      domains of acoustic features. Firstly, the voice pitch of males and females
      congruate one to another, while range and variability both increase. The values
      of jitter, shimmer and harmonics-to-noise ratio (measures of microstability of
      frequency, amplitude and waveform resp.) reflect a growing voice instability.
      From all spectral characteristics, only the difference between the first and the
      second harmonic differs significantly when comparing young to old women.

PMID- 9241378
TI  - Acute mastoiditis with complications: a report of two cases.
AB  - The authors report two cases of lateral sinus thrombosis (LST) which were
      recently observed after more than a 20-year absence of such pathology at their
      Institutions. After reviewing the epidemiologic data, the clinical observations
      are described in detail. Changes in symptomatology mainly due to the improper use
      of antibiotics are then discussed as well as the diagnostic improvement offered
      by modern imaging techniques. Problems still under debate concern the therapeutic
      strategy: internal jugular vein ligation or anticoagulation therapy versus
      aminoglycoside administration for patients refractory to the conventional
      antibiotic therapy. The necessity of close cooperation between general
      practitioner, pediatrician and otolaryngologist is stressed.

PMID- 9241379
TI  - Labyrinthine fistulae: a retrospective analysis.
AB  - A retrospective analysis has been conducted of 57 labyrinthine fistulae found in
      375 cholesteatoma cases, primarily treated by removal of the matrix of the
      cholesteatoma and covering the fistula with a mixture of bone paste and fibrin
      glue. CT-scan with slices of 1 mm demonstrated the fistula in almost 90% of the
      cases. Eighteen percent of the ears were pre-operatively totally deaf. Large
      fistulae are riskier than smaller ones for post-operative perceptive losses, but
      even in very large and multiple fistulae the hearing may be preserved in most
      cases.

PMID- 9241380
TI  - The vestibular neurectomy by retrosigmoid approach: operative technique and
      results.
AB  - A vestibular neurectomy is indicated in all cases of persistent vertigo without
      central vestibular compensation, with or without hearing loss. The retrosigmoid
      approach is described, as well as the postoperative results in 12 patients. The
      results are compared with those of other surgical treatments.

PMID- 9241381
TI  - The Gender and Tropical Diseases Task Force of TDR: achievements and challenges.

PMID- 9241382
TI  - In vitro trypanocidal activity of some rare Tanzanian medicinal plants.
AB  - Extracts prepared from 15 rare Tanzanian medicinal plants were tested for their
      in vitro antitrypanosomal activity against human pathogenic trypanosomes
      (Trypanosoma brucei rhodesiense). Of 37 extracts investigated, two were found to
      have strong activity with IC50 values below 1 microgram/ml and ten extracts
      revealed promising activities with IC50 values between 1 and 5 micrograms/ml.

PMID- 9241383
TI  - Identification of trypanosomes isolated by KIVI from wild mammals in Cote
      d'Ivoire: diagnostic, taxonomic and epidemiological considerations.
AB  - In Cote d'Ivoire, a comparative study was carried out on 122 wild mammals by
      parasitological and serological examination and by in vitro isolation of
      trypanosomes from fresh blood (KIVI). Thirteen isolated stocks were studied by
      isoenzymes and compared with Trypanosoma congolense and T. brucei bouafle group
      reference stocks. Of the 122 animals, only 22 were positive on blood smears while
      88 were KIVI positive and 92 were CATT/T. b. gambiense positive. For six stocks
      identified by isoenzymes as T. congolense, the agreement between ELISA and CATT
      was good (75%). As compared with CATT, antigen detection ELISA was not
      satisfactory for T. brucei (20%). Out of 18, 16 stocks represented a separate
      zymodeme (seven T. congolense and nine T. brucei) and a high genetic
      heterogeneity was observed. For T. congolense, savanna, kilifi and forest groups
      were represented by one zymodeme each. The four remaining zymodemes while put
      into this T. congolense group, were strongly independent of each other.
      Morphology indicated that those new zymodemes correspond to T. congolense. In the
      other hand, five new zymodemes fit into T. brucei classification.

PMID- 9241384
TI  - Monotherapy with sodium artesunate for uncomplicated falciparum malaria in
      Thailand: a comparison of 5- and 7-day regimens.
AB  - We compared the safety and efficacy of two treatment regimens using sodium
      artesunate in 91 randomized patients with uncomplicated falciparum malaria
      acquired in Thailand. One group of 45 patients received 400 mg of artesunate on
      the first day of treatment and then 200 mg daily for 4 days for a total of 1200
      mg (group I: 5-day treatment). A second group of 46 patients received 400 mg of
      artesunate on the first day of treatment and then 200 mg daily for 6 days for a
      total of 1600 mg (group II: 7-day treatment). Both regimens were well tolerated.
      All patients were followed for a total of 28 days. By the third day of treatment,
      most patients were blood smear negative for parasites. Eighty-two patients
      completed the 28-day follow-up period and were used for describing the cure rate.
      All patients treated with the 5-day regimen were cured. In the 7-day treatment
      group, 98% (39 of 40) of the patients were cured; one patient developed late
      recrudescence (RI). There were no significant differences in fever clearance or
      parasite clearance between the two groups. However, 13 patients (five in group I
      and eight in group II) developed Plasmodium vivax infection during the follow-up
      period. We conclude that 5- or 7-day regimens of sodium artesunate with a total
      dose of 1200-1600 mg are effective and safe in treating falciparum malaria
      acquired in Thailand.

PMID- 9241385
TI  - Antimalaria activity of the triple combination of proguanil, atovaquone and
      dapsone.
AB  - The combination of proguanil and atovaquone has been shown to be more effective
      in curing drug-resistant infections of falciparum malaria than atovaquone or
      proguanil alone. Our current study sought to determine whether the antimalaria
      activity could be increased by adding dapsone. Plasma samples, obtained from
      individuals 4-72 h after proguanil-atovaquone administration, were 2-3 times more
      active against Plasmodium falciparum in vitro when dapsone was added to them. The
      enhanced activity of the combination of proguanil, atovaquone and dapsone is
      probably due to the combined activity of two synergistic combinations: proguanil
      atovaquone and cycloguanil (metabolite of proguanil)-dapsone. These findings
      suggest that further studies are needed to evaluate the clinical value of the
      triple drug combination of proguanil, atovaquone and dapsone in the treatment of
      multi-drug resistant malaria.

PMID- 9241386
TI  - SPf66 malaria vaccine is safe and immunogenic in malaria naive adults in
      Thailand.
AB  - In preparation for an efficacy trial of malaria vaccine SPf66 in Thailand, a
      series of overlapping Phase I trials were conducted of US-manufactured SPf66.
      Here, two clinical lots were evaluated for safety and immunogenicity in a
      combined open-label trial. Eleven healthy, malaria naive, 18-44 year-old Thai men
      and women received three doses by subcutaneous injection in alternate arms at 0,
      1 and 6 months. Safety was assessed by monitoring local and systemic
      reactogenicity and laboratory parameters. Common side effects were mild erythema,
      induration and tenderness at the site of injection which resolved within 24-48 h.
      At third immunization, two volunteers developed acute bilateral reactions with
      induration, erythema and pruritus limited to the sites of the second and third
      immunizations. Eight of 11 volunteers sero-converted by ELISA, six of whom would
      be classified as high responders by Colombian standards. Eight of 11 volunteers
      developed a lymphoproliferative response to the SPf66 antigen. Side effects were
      more common and antibody and lymphoproliferative responses greatest, among the
      four female volunteers. This initial study of SPf66 malaria vaccine in Asia
      constitutes an essential link between the initial Phase I study in the US and
      subsequent field studies in a semi-immune population in a malaria endemic area of
      Thailand. This study further establishes comparability of US-manufactured SPf66
      with that of Colombian provenance and substantiates the validity of the
      subsequent negative efficacy results of SPf66 in a field trial in Thailand.

PMID- 9241387
TI  - A subtropical case of human babesiosis.
AB  - This report constitutes the first well-documented case of symptomatic human
      babesiosis from a subtropical site, south of the 40th parallel. This paper
      describes the definitive identification of Babesia divergens infection in a
      splenectomized patient from the Canary Islands.

PMID- 9241388
TI  - Factors associated with client-reported HIV infection among clients entering
      methadone treatment.
AB  - To determine demographic and behavioral factors associated with client-reported
      HIV infection among new enrollees in methadone maintenance treatment programs
      (MMTPs) in Massachusetts and Connecticut, we examined ethnographic data and
      interview data from MMTP clients (N = 674). Clients responded to questions about
      behaviors in the 30 days before drug treatment. ETHNOGRAPH was used to analyze
      qualitative data, and logistic regression analysis was used to identify variables
      associated with client-reported HIV infection. Statistical significance was set
      at p < .05. The client-reported HIV infection rate was 20% (132/674). Odds ratios
      for factors associated with client-reported HIV infection were being white
      (0.53), increase in age (1.07), use of non-injected heroin (0.12), use of
      injected heroin (6.24), cocaine injection (1.78), sharing of "works" with
      strangers (2.15), and "safer sex" behavior (4.04). Additionally, 35% of those who
      did not use illicit drugs reported being seropositive. The qualitative data
      suggested HIV positive clients were concerned about protecting sex partners, and
      learning of HIV infection motivated some to stop using drugs. Although some
      clients engaged in low-risk behaviors, others did not, therefore the potential
      for HIV transmission among injection drug users (IDUs) in Connecticut and
      Massachusetts exists. HIV prevention and drug treatment program personnel should
      reinforce and build on the low-risk behaviors that are acceptable and adopted by
      some in this population.

PMID- 9241389
TI  - Ethnic differences in the association between behavior with a new partner: an
      event-based analysis.
AB  - The relationship of alcohol consumption to risky sexual behavior at the most
      recent encounter with a new sexual partner in representative samples of white,
      Hispanic, and black adults was examined. Drinking at the new partner event was
      more prevalent among whites than either blacks or Hispanics. Multivariate
      analyses indicated that drinking in the event was an important predictor on
      having a casual partner and using condoms with a casual partner for men but not
      for women. For women, drinking during the event predicted failure to use a
      condom. Some of these associations were dependent on ethnicity. Hispanics who
      consumed alcohol at the encounter were more likely to engage in protected sex
      than whites or blacks. These findings suggest that alcohol is but one of many
      influences regulating the riskiness of a particular encounter with a new partner
      and that the interplay of personal, situational, and behavioral factors with
      risky sex are culturally dependent.

PMID- 9241390
TI  - Do homosexual and bisexual men who place others at potential risk for HIV have
      unique psychological profiles?
AB  - Prevention of HIV infection requires individuals to attend not only to their own
      risk but also whether they place others at risk. To design appropriate
      interventions, however, it is important to determine whether HIV positive and HIV
      negative individuals who place others at potential risk differ in their
      psychological profiles. Such differences would suggest the need for specially
      tailored interventions for each group. We studied 525 homosexual and bisexual men
      (156 HIV positive, 369 HIV negative) from the Multicenter AIDS Cohort Study
      (Pittsburgh site) to (a) identify correlates of risky behavior and (b) determine
      whether these correlates differed by HIV serostatus. Although HIV positive men
      were somewhat less likely than HIV negative men to have engaged in high-risk
      sexual activity in the past 6 months (e.g., unprotected insertive anal
      intercourse), the correlates of such activity were identical across groups.
      Regardless of serostatus, men placing others at potential risk were younger, less
      educated, had less psychological distress and greater feelings of mastery,
      employed fewer active behavioral coping strategies, and were heavier users of
      alcohol and amyl nitrate (poppers).

PMID- 9241391
TI  - Assessing the impact of HIV risk reduction counseling in impoverished African
      American women: a structural equations approach.
AB  - We assessed changes in cognitive, psychological, and risky behavior latent
      variables after traditional or specialized AIDS education after 2 years using
      structural equation modeling (SEM) in a sample of impoverished at-risk African
      American women (N = 300). Both groups reported significant improvement at 2 years
      in their self-esteem and social resources. They also reported less threat
      perception, avoidant coping, emotional disturbance, HIV risk behavior, and drug
      use behavior. There was an advantage to specialized group membership. When
      compared with the traditional group at 2 years, women in the specialized group
      reported enhanced social resources, reduced emotional distress, less use of an
      avoidant coping style, and less drug use. We discuss advantages of culturally
      sensitive HIV risk reduction programs and the importance of connecting women with
      social services in their communities.

PMID- 9241392
TI  - The role of psychosocial assessment and support in occupational exposure
      management.
AB  - Hundreds of thousands of occupational exposures to the blood and body fluids of
      patients occur every year in health care settings. The risk of acquiring HIV
      infection after exposure to HIV infected blood is 0.452%. Despite this low risk,
      the impact of each of these exposures is significant to the health care worker
      who is exposed. This paper focuses on the importance of adapting HIV education
      and counseling models to occupational settings. It recommends the incorporation
      of psychosocial assessment, risk reduction education, counseling, and support
      into existing exposure management programs. Barriers to effective occupational
      exposure counseling and their possible solutions are examined. Case studies are
      used to illustrate the complex issues raised during counseling.

PMID- 9241393
TI  - Children's AIDS-related knowledge and attitudes: variations by grade, race,
      gender, socioeconomic status, and size of community.
AB  - Variations of AIDS-related beliefs by grade, race, gender, socioeconomic status,
      and size of the community were examined for a diverse group of elementary school
      children (n = 609). Consistent with prior research, beliefs about HIV
      transmission and willingness to interact with persons with AIDS increased across
      grades 1 to 5. Black children living in rural communities held most
      misconceptions about AIDS and, relative to white peers, black children were more
      reluctant to interact with persons with AIDS (PWA). Support for more negative
      attitudes toward PWA among boys was also found. Knowledge of transmission
      mediated grade and sex differences in willingness to interact, but not race
      differences. Implications of results for AIDS prevention programs are discussed,
      along with directions for future research.

PMID- 9241394
TI  - HIV counseling and testing: its evolving role in HIV prevention.
AB  - The development of an enzyme-linked immunosorbent assay (ELISA) for screening
      blood for antibodies to HIV was a major milestone in the history of AIDS
      prevention and treatment. Since early 1985, the Centers for Disease Control and
      Prevention (CDC) has provided public funds to state and local health departments
      to support a national HIV counseling-and-testing (HIV CT) program directed toward
      persons at risk of transmitting or becoming infected with HIV. The implementation
      and ongoing development of this national program has often been marked by intense
      policy debate, especially in the area of mandatory testing. Furthermore, the
      lessons learned during its 11-year program history are highly relevant to
      understanding the challenges that might arise when implementing other new
      biomedical or behavioral HIV prevention technologies. Using the construct of
      public health infrastructure, this article describes key features, events,
      lessons learned, and future challenges of this evolving national prevention
      program.

PMID- 9241396
TI  - Advances in HIV testing technology and their potential impact on prevention.
AB  - Recent advances in HIV testing technology are increasing options for HIV testing
      which may lead to more persons at risk for HIV infection learning their
      serostatus. These advances include the development of simple rapid assays with
      visual reading, several of which can be used with whole blood (including finger
      stick) or with non-invasive alternative specimens like oral fluids or urine. Many
      of these new tests are simple enough to be used in nonclinical settings by public
      health workers or by consumers in the home. For some of these developments, such
      as rapid testing, enough is now known to recommend their use within specific
      clinical contexts. For other developments, such as home sample collection,
      understanding their true impact must wait for postmarketing evaluation. For
      technologies currently in development, such as true home testing, we are only
      beginning to understand and address the issues. We, as clinicians and public
      health practitioners who are interested in prevention, must begin to deal with
      the issues. We must identify important policy questions, develop a research
      agenda to begin to answer these questions, and devise strategies to maximize the
      opportunities for HIV prevention and minimize the potential for harm.

PMID- 9241395
TI  - Concepts, goals, and techniques of counseling: review and implications for HIV
      counseling and testing.
AB  - Research to examine, understand, and improve the usefulness and effectiveness of
      HIV counseling and testing (HIV CT) has been challenging, to some extent because
      of a less than fully articulated conceptual framework. The goal of this article
      is to place HIV CT in a conceptual and theoretical context, not only of
      counseling and psychotherapy but also of a larger framework of models of behavior
      change. Counseling approaches are also compared with respect to how well they
      address five tasks of HIV counseling: relationship building, risk assessment,
      dissemination of information, behavior change, and emotional and coping support.
      No single counseling approach was found to meet all of these tasks. Behavioral
      and cognitive-behavioral approaches were considered most relevant to the tasks of
      HIV counseling, whereas client-centered and crisis counseling approaches were
      appropriate for the relationship building and emotional/coping support components
      of HIV counseling. In addition, this article provides a more differentiated view
      of HIV CT and suggests how further research into the effectiveness of HIV
      counseling can be informed by primary underlying counseling theories.

PMID- 9241397
TI  - It's like a regular part of gay life: repeat HIV antibody testing among gay and
      bisexual men.
AB  - HIV antibody testing is a critical facet of national AIDS prevention strategies
      and increasing numbers of persons are tested each year. Research has shown that a
      significant number of men who have sex with men are repeatedly tested for HIV
      antibodies, and many are tested regularly every 6 months. This study investigated
      the prevalence of repeat testing (having been tested three or more time) and
      regular testing (having been tested three or more times and getting tested every
      6 months), and their association to testing attitudes and sexual behaviors. We
      found that 66% of 253 HIV seronegative gay and bisexual men surveyed at a large
      gay pride festival had been repeatedly tested, and 47% were tested regularly.
      Repeat testing was associated with knowing people with HIV or AIDS, whereas
      regular testing was associated with younger age and not being in an exclusive
      sexual relationship. Both repeat and regular testers held more positive health
      related attitudes about testing than nonrepeat and nonregularly tested men,
      respectively. Contrary to previous research, repeat testing was not associated
      with unprotected anal intercourse or unprotected oral sex. However, both repeat
      and regular testing were positively related to condom use during anal intercourse
      as well as having multiple protected anal intercourse partners. We therefore
      conclude that both repeat testing and higher rates of condom use reflect positive
      health attitudes and that repeat testing may function to meet the needs of some
      men who have sex with men.

PMID- 9241398
TI  - The effects of HIV counseling and testing on risk-related practices and help
      seeking behavior.
AB  - In an earlier review of the behavioral effects of HIV counseling and testing (HIV
      CT), Higgins and colleagues (1991) found that the evidence regarding the ability
      of HIV CT to influence HIV-risk related practices was largely inconclusive. This
      article reviews 35 domestic and international studies published since that time
      to reassess the scientific data regarding the ability of HIV CT to motivate
      changes in risk-related practices and to promote help-seeking behavior. The
      studies identified for this review were grouped into four categories according to
      subject population: (1) men who have sex with men, (2) injection and other drug
      users, (3) women and heterosexual couples, and (4) mixed samples recruited from
      sexually transmitted disease (STD) clinics and other settings. Findings from the
      studies reviewed were generally mixed--many provided at least some evidence
      supporting the ability of HIV CT to motivate risk-reducing and help-seeking
      behavior, but others did not. The pattern of results varied substantially across,
      and within, study populations and were often limited by considerable
      methodological weaknesses.

PMID- 9241399
TI  - Partner notification for HIV prevention: a critical reexamination.
AB  - The history, current role, and potential enhanced functions of HIV partner
      notification are reviewed. What is known about the effectiveness of partner
      notification is summarized and five general findings are reported: (1) many, if
      not most, HIV-infected individuals will cooperate in notifying at least some of
      their sex partners of exposure to HIV; (2) sex partners are generally receptive
      to being notified and will seek HIV testing; (3) patient referral is probably not
      as effective as provider referral in reaching sex partners; (4) sex partners
      often are unaware of or misunderstand their HIV risks; and (5) sex partners
      frequently have high rates of HIV infection. Means for enhancing partner
      notification are reviewed, including social network interventions, coupling
      partner notification with behavioral interventions, reaching persons earlier in
      their HIV infection, using data collected from partner notification as a source
      of program evaluation information, and addressing important community concerns
      about partner notification.

PMID- 9241400
TI  - Publicly funded HIV counseling and testing in the United States, 1992-1995.
AB  - Data are collected and reported through the Centers for Disease Control and
      Prevention (CDC) Counseling and Testing System (CTS) on episodes of publicly
      funded counseling and HIV testing in the Unites States. The objective of this
      analysis is to describe testing data reported from 1992 through 1995. In 1992,
      2,689,056 tests were performed, and 55,024 (2.0%) were positive; in 1995,
      2,491,434 tests were performed, of which 40,605 (1.6%) were positive. Among tests
      reported with client-level data, the proportion of tests of men and women at
      higher risk for HIV infection remained stable or declined; the proportion of
      tests of persons who had been previously tested increased each year; and in 1995,
      the proportion of tests that included posttest counseling was 86% for anonymous
      and 70% for confidential tests. Although information collected through CTS could
      be improved by changing the system so that individuals could be distinguished
      from testing episodes, the CTS does provide important monitoring information to
      local and state health departments.

PMID- 9241401
TI  - The role of HIV counseling and testing in the developing world.
AB  - The role of voluntary HIV counseling and testing is still under debate,
      especially in the developing world. HIV counseling-and-testing (HIV CT) services
      are a major component of HIV and AIDS control programs in the industrialized
      world and are increasingly being advocated in the developing world. In the United
      States, voluntary HIV CT has been a major component of HIV prevention efforts
      since the HIV antibody test became available in 1985. Yet even in the United
      States, questions about the management, cost, and effectiveness of voluntary HIV
      CT services continue to be raised. Because HIV CT has multiple goals, the
      evaluation of its effectiveness is a complicated task. Worldwide, a broad range
      of ethical, social, policy, technical, and economic issues encompass this HIV
      prevention activity. This article identifies the substantial barriers and serious
      concerns that are raised about HIV CT services and attempts to highlight the
      potential advantages of providing HIV CT as part of a developing country's
      comprehensive HIV prevention strategy.

PMID- 9241402
TI  - The evaluation of HIV counseling-and-testing services: making the most of limited
      resources.
AB  - The evaluation of HIV counseling, testing, referral, and partner notification
      (CTRPN) services are especially important given the rapid, relevant changes in
      counseling strategies, public policies, and testing technologies. Here we briefly
      review the important components of a comprehensive HIV CTRPN evaluation. However,
      resources for evaluation are usually quite limited, thus making comprehensive
      evaluations impossible. Yet even with limited resources, meaningful evaluative
      activities can be performed and some pressing evaluation questions answered. As
      an illustration, we present a practical evaluation project (conducted with
      limited resources) that assessed at a systems level the HIV counseling and
      testing (HIV CT) program in the state of Wisconsin. We describe how some of this
      evaluative information was utilized by the state's division of health.

PMID- 9241403
TI  - Beliefs about social integration from the perspectives of persons with mental
      retardation, job coaches, and employers.
AB  - Beliefs of multiple stakeholders who were all part of the same "transition
      community" (including persons with mental retardation, job coaches, and
      employers) about social integration outcomes and interventions in employment
      settings were examined. Data were collected through interviews and questionnaires
      that were designed based on a previously affirmed conceptual framework of social
      integration. Although results showed that stakeholders agreed on some outcomes
      and interventions they disagreed on others. These disagreements could be cause
      for concern because contrasting belief systems among stakeholders supposedly
      working toward the same goal might interfere with successful social integration
      in work settings for persons with mental retardation.

PMID- 9241404
TI  - Aging families of adults with mental retardation: patterns and correlates of
      service use, need, and knowledge.
AB  - Older mothers (N = 235, mean age = 70.3) of adult offspring were surveyed to
      identify patterns and correlates of the extent to which their families either
      used, knew about, needed, or had unmet needs for 17 family support services.
      Although variability was observed across these services, overall level of service
      use was low despite high knowledge. Also, the number of services needed exceeded
      number of services actually used. Greater service use occurred when offspring
      were younger, female, came from lower income households, and were receiving high
      levels of care from mothers who reported higher subjective burden and self
      reported health. Families had larger unmet service needs when mothers were
      married, received less assistance from their children without mental retardation,
      and reported higher levels of subjective burden.

PMID- 9241405
TI  - Transitory hyperphenylalaninaemia in children with continuously treated
      phenylketonuria.
AB  - Cognitive and behavioral effects of temporarily challenging the CNS with elevated
      levels of phenylalanine in treated phenylketonuria (PKU) were investigated in a
      triple-blind, cross-over study. A high phenylalanine supplement was given over 3
      months to sixteen 10- to 16-year-old early and continuously treated children with
      classical PKU. We used the WISC and Rivermead tests to measure cognitive function
      and the Rutter Scales to assess disordered behavior. Parents and children guessed
      at the condition imposed. The Group x Phase interaction for phenylalanine level
      was statistically significant, but this pattern was not mirrored in the
      psychological test data, and guessing was random. Results suggest that
      intellectual ability, memory, and conduct are not affected by medium-term
      hyperphenylalaninaemia in PKU after 10 or more years of treatment.

PMID- 9241406
TI  - Personal characteristics associated with episodes of injury in a residential
      facility.
AB  - Number of episodes of injury and personal characteristics of 412 individuals
      living in a state-operated ICF/MR during 1994 were examined. Results indicated
      that 16% of the facility population experienced 67% of the injuries. Discriminant
      functions were created using chlorpromazine equivalent level combined with
      maladaptive behavior, medical, and adaptive behavior factors to classify
      individuals into high and low injury groups. Individuals taking antipsychotics,
      having higher maladaptive behavior scores, and having relatively higher levels of
      adaptive behavior were most likely to be in the high injury group. We concluded
      that episodes of injury were not evenly distributed across the individuals and
      certain personal characteristics discriminated high from low risk groups.

PMID- 9241408
TI  - Interobserver agreement and disagreement in continuous recording exemplified by
      measurement of behavior state.
AB  - Continuous observational recording was used to measure behavior state of 3 adults
      with profound and multiple disabilities. Observations were made over 56.7 hours,
      including 21.9 hours with two observers recording independently. Overall
      percentage agreement was satisfactory (i.e., exceeded 80%). Agreement on
      occurrence was, however, generally unsatisfactory at a mean of 63.5%, with 5 of
      16 Subject x State Agreement Indices over 80%. Percentage disagreement on
      occurrence, a previously unreported measure, was computed to quantify sources of
      disagreement. The agreement data were superimposed on participants' behavior
      state profiles to demonstrate how conclusions can be drawn from the data, despite
      their generally inadequate reliability. This approach to interobserver agreement
      and presentation of data is suggested for researchers investigating entities that
      are not directly amenable to observation.

PMID- 9241407
TI  - Behavioral and emotional disturbance in individuals with Williams syndrome.
AB  - Behavioral and emotional disturbance was assessed in 70 children and adolescents
      with Williams syndrome. They were compared with an epidemiological control
      population, which was statistically controlled for age, gender, and level of
      mental retardation. Those with Williams syndrome were more likely to be diagnosed
      as suffering psychiatric disorder. The disorder was characterized by anxiety,
      hyperactivity, preoccupations, and inappropriate interpersonal relating.
      Significantly increased rates of other individual symptoms were also found,
      including sleep disturbance and hyperacusis. These results, considered with
      earlier findings, suggest that there is a valid behavior phenotype of Williams
      syndrome. This is frequently associated with sufficient impairment to consider
      inclusion of the behavior phenotype in future official taxonomies of mental
      disorders.

PMID- 9241409
TI  - Direct and indirect behavioral effects of different genetic disorders of mental
      retardation.
AB  - Direct and indirect behavioral effects of genetic disorders of mental retardation
      were identified. Three models of direct effects were examined: the no-specific
      effect model (all genetic disorders lead to identical behavioral outcomes), the
      totally specific model (each genetic disorder leads to unique outcomes), and the
      partially specific model (two or more genetic disorders lead to outcomes not
      shared by others with mental retardation). Although several cases of totally
      specific outcomes have been identified, partially specific effects most often
      occur. Persons in the surrounding environment are indirectly affected by
      behavioral propensities of different genetic disorders. Direct and indirect
      effects are also related to biological and developmental theory.

PMID- 9241411
TI  - Whatever happened to the fun? An autobiographical investigation.

PMID- 9241410
TI  - Use of psychotropic medication in Oklahoma: a statewide survey.
AB  - Analysis of statewide survey data revealed that 22.5% of individuals with mental
      retardation who were served by the Oklahoma mental retardation system were
      receiving antipsychotic medication. Anxiolytic medications were prescribed for
      9.3%, and antidepressants were prescribed for 5.9%. Higher levels of medication
      use were found in institutional settings and Intermediate Care Facility settings.

PMID- 9241412
TI  - Structural and mechanistic determinants of affinity and specificity of ligands
      discovered or engineered by phage display.
AB  - The scope and utility of phage display is reviewed with emphasis on medical
      applications and structure-based ligand and drug design, from literature mostly
      after 1994. General principles by which phage-displayed peptides achieve affinity
      and selectivity for targets are described, along with selected structural or
      mechanistic studies of the binding of peptides or proteins discovered or
      engineered by phage display. Such engineered proteins whose wild-type or mutant
      crystal or 2D-NMR structures yield insight about the basis for enhanced affinity
      or altered specificity include antibodies, zinc fingers, human growth hormone,
      protein A, and atrial natriuretic peptide. Structures of complexes of de novo
      phage-discovered peptide ligands with targets such as the Src SH3 domain,
      streptavidin, and erythropoietin receptor reveal the structural basis for
      receptor-peptide recognition in these systems.

PMID- 9241413
TI  - Calcium in close quarters: microdomain feedback in excitation-contraction
      coupling and other cell biological phenomena.
AB  - Researchers have made good progress in unraveling the molecular mechanisms of
      excitation-contraction (EC) coupling in striated muscle. Despite this progress,
      paradoxes abound. In skeletal muscle, the existence of a mechanical coupling
      between membrane charge movement and activation of sarcoplasmic reticulum (SR)
      release channels is essentially established, but the contribution of Ca(2+)
      induced Ca2+ release (CICR) to the transient and steady-state components of Ca2+
      release remains controversial. In cardiac muscle, the role of CICR as the primary
      mechanism of EC coupling is well established, but the stability and tight
      coupling between membrane Ca2+ current and release are paradoxical. Answers may
      lie in microdomain issues, and the examination of discrete elementary release
      events, although quantitative treatments are needed. This review explores the
      theoretical and experimental methods used and the observations made in the study
      of microdomain Ca2+.

PMID- 9241414
TI  - Histone structure and the organization of the nucleosome.
AB  - Chromatin structure is now believed to be dynamic and intimately related with
      cellular processes such as transcription. Over the past few years, high
      resolution structures for the histones have become available. These structures
      and their implications for nucleosome organization are reviewed here.

PMID- 9241415
TI  - Hierarchy and dynamics of RNA folding.
AB  - The evidence showing that the self-assembly of complex RNAs occurs in discrete
      transitions, each relating to the folding of sub-systems of increasing size and
      complexity starting from a state with most of the secondary structure, is
      reviewed. The reciprocal influence of the concentration of magnesium ions and
      nucleotide mutations on tertiary structure is analyzed. Several observations
      demonstrate that detrimental mutations can be rescued by high magnesium
      concentrations, while stabilizing mutations lead to a lesser dependence on
      magnesium ion concentration. Recent data point to the central controlling and
      monitoring roles of RNA-binding proteins that can bind to the different folding
      stages, either before full establishment of the secondary structure or at the
      molten globule state before the cooperative transition to the final three
      dimensional structure.

PMID- 9241416
TI  - Flexibility of RNA.
AB  - One of the fundamental properties of the RNA helix is its intrinsic resistance to
      bend- or twist-deformations. Results of a variety of physical measurements point
      to a persistence length of 700-800 A for double-stranded RNA in the presence of
      magnesium cations, approximately 1.5-2.0-fold larger than the corresponding value
      for DNA. Although helix flexibility represents an important, quantifiable measure
      of the forces of interaction within the helix, it must also be considered in
      describing conformational variation of nonhelix elements (e.g. internal loops,
      branches), since the latter always reflect the properties of the flanking
      helices; that is, such elements are never completely rigid. For one important
      element of tertiary structure, namely, the core of yeast tRNAPhe, the above
      consideration has led to the conclusion that the core is not substantially more
      flexible than an equivalent length of pure helix.

PMID- 9241417
TI  - Structural perspectives of phospholamban, a helical transmembrane pentamer.
AB  - Phospholamban is a 52-amino-acid protein that assembles into a pentamer in
      sarcoplasmic reticulum membranes. The protein has a role in the regulation of the
      resident calcium ATPase through an inhibitory association that can be reversed by
      phosphorylation. The phosphorylation of phospholamban is initiated by beta
      adrenergic stimulation, identifying phospholamban as an important component in
      the stimulation of cardiac activity by beta-agonists. In this role of
      phospholamban that has motivated studies in recent decades. There is evidence
      that phospholamban may also function as a Ca(2+)-selective ion channel. The
      structural properties of phospholamban have been studied by mutagenesis,
      modeling, and spectroscopy, resulting in a new view of the organization of this
      key molecule in membranes.

PMID- 9241418
TI  - Biomolecular dynamics at long timesteps: bridging the timescale gap between
      simulation and experimentation.
AB  - Innovative algorithms have been developed during the past decade for simulating
      Newtonian physics for macromolecules. A major goal is alleviation of the severe
      requirement that the integration timestep be small enough to resolve the fastest
      components of the motion and thus guarantee numerical stability. This timestep
      problem is challenging if strictly faster methods with the same all-atom
      resolution at small timesteps are sought. Mathematical techniques that have
      worked well in other multiple-timescale contexts--where the fast motions are
      rapidly decaying or largely decoupled from others--have not been as successful
      for biomolecules, where vibrational coupling is strong. This review examines
      general issues that limit the timestep and describes available methods
      (constrained, reduced-variable, implicit, symplectic, multiple-timestep, and
      normal-mode-based schemes). A section compares results of selected integrators
      for a model dipeptide, assessing physical and numerical performance. Included is
      our dual timestep method LN, which relies on an approximate linearization of the
      equations of motion every delta t interval (5 fs or less), the solution of which
      is obtained by explicit integration at the inner timestep delta tau (e.g., 0.5
      fs). LN is computationally competitive, providing 4-5 speedup factors, and
      results are in good agreement, in comparison to 0.5 fs trajectories. These
      collective algorithmic efforts help fill the gap between the time range that can
      be simulated and the timespans of major biological interest (milliseconds and
      longer). Still, only a hierarchy of models and methods, along with
      experimentational improvements, will ultimately give theoretical modeling the
      status of partner with experiment.

PMID- 9241419
TI  - Molecular mechanism of photosignaling by archaeal sensory rhodopsins.
AB  - Two sensory rhodopsins (SRI and SRII) mediate color-sensitive phototaxis
      responses in halobacteria. These seven-helix receptor proteins, structurally and
      functionally similar to animal visual pigments, couple retinal photoisomerization
      to receptor activation and are complexed with membrane-embedded transducer
      proteins (HtrI and HtrII) that modulate a cytoplasmic phosphorylation cascade
      controlling the flagellar motor. The Htr proteins resemble the chemotaxis
      transducers from Escherichia coli. The SR-Htr signaling complexes allow studies
      of the biophysical chemistry of signal generation and relay, from the
      photobiophysics of initial excitation of the receptors to the final output at the
      level of the flagellar motor switch, revealing fundamental principles of sensory
      transduction and more broadly the nature of dynamic interactions between membrane
      proteins. We review here recent advances that have led to new insights into the
      molecular mechanism of signaling by these membrane complexes.

PMID- 9241420
TI  - Modular peptide recognition domains in eukaryotic signaling.
AB  - A characteristic feature of cellular signal transduction pathways in eukaryotes
      is the separation of catalysis from target recognition. Several modular domains
      that recognize short peptide sequences and target signaling proteins to these
      sequences have been identified. The structural bases of the specificities of
      recognition by SH2, SH3, and PTB domains have been elucidated by X-ray
      crystallography and NMR, and these results are reviewed here. In addition, the
      mechanism of cooperative interactions between these domains is discussed.

PMID- 9241421
TI  - Eukaryotic transcription factor-DNA complexes.
AB  - Eukaryotes have three distinct RNA polymerases that catalyze transcription of
      nuclear genes. RNA polymerase II is responsible for transcribing nuclear genes
      encoding the messenger RNAs and several small nuclear RNAs. Like RNA polymerases
      I and III, polymerase II cannot recognize its target promoter directly and
      initiate transcription without accessory factors. Instead, this large
      multisubunit enzyme relies on general transcription factors and transcriptional
      activators and coactivators to regulate transcription from class II promoters. X
      ray crystallography and nuclear magnetic resonance spectroscopy have been used to
      study complexes of general transcription factors and transcriptional activators
      with their specific DNA targets. This work has provided important structural
      insights into transcription initiation by polymerase II and the more general
      problem of DNA sequence recognition.

PMID- 9241422
TI  - Nanosecond time-resolved spectroscopy of biomolecular processes.
AB  - Over the past two decades, nanosecond absorption and vibrational spectroscopies
      have developed into powerful tools for monitoring the secondary, tertiary, and
      quaternary structural relaxations of biological macromolecules under near
      physiological conditions of solvent and temperature. Observed through such
      methods, the dynamic response of a biomolecule to photoinitiated excursions from
      equilibrium can reveal valuable information about the structure-function
      relationship, information beyond that obtained from the static structures
      provided by X-ray crystallography, nuclear magnetic resonance spectroscopy, and
      other steady-state methods. Most recently, the development of ultra-sensitive
      polarization techniques for absorption spectroscopy has greatly enhanced the
      amount of time-resolved structural information that can be obtained from the
      broadened electronic spectra of biomolecules. This review examines nanosecond
      absorption, vibrational, and polarized absorption methods, and their applications
      to protein function and folding, emphasizing the complementary nature of
      information obtained from electronic and vibrational spectra measured on the
      nanosecond time scale.

PMID- 9241423
TI  - Lessons from zinc-binding peptides.
AB  - Zinc-finger domains are small metal-binding modules that are found in a wide
      range of gene regulatory proteins. Peptides corresponding to these domains have
      provided valuable model systems for examining a number of biophysical parameters
      entirely unrelated to their nucleic acid binding properties. These include the
      chemical basis for metal-ion affinity and selectivity, thermodynamic properties
      related to hydrophobic packing and beta-sheet propensities, and constraints on
      the generation of ligand-binding and potential catalytic sites. These studies
      have laid the foundation for applications such as the generation of optically
      detected zinc probes and the design of metal-binding peptides and proteins with
      desired spectroscopic and chemical properties.

PMID- 9241424
TI  - Single-particle tracking: applications to membrane dynamics.
AB  - Measurements of trajectories of individual proteins or lipids in the plasma
      membrane of cells show a variety of types of motion. Brownian motion is observed,
      but many of the particles undergo non-Brownian motion, including directed motion,
      confined motion, and anomalous diffusion. The variety of motion leads to
      significant effects on the kinetics of reactions among membrane-bound species and
      requires a revision of existing views of membrane structure and dynamics.

PMID- 9241425
TI  - Bacteriophage display and discovery of peptide leads for drug development.
AB  - Phage display makes large-peptide diversity libraries readily attainable for
      identifying novel peptide ligands for receptors and other protein or non-protein
      targets. This technology kindles enthusiasm for the idea that large and protein
      protein interaction surfaces (epitopes) can be distilled down to small
      pharmacophores. These may be accessible to organic scaffolding, yielding new
      orally active drugs that might otherwise have taken greater time and effort to be
      discovered through chemical-library screening. This review, though not
      comprehensive with respect to the explosive volume of phage display work over the
      last few years, focuses on recent developments in phage-displayed peptide
      technology.

PMID- 9241426
TI  - Solvation: how to obtain microscopic energies from partitioning and solvation
      experiments.
AB  - Oil-water partitioning, solubilities, and vapor pressure experiments on small
      molecule compounds are often used as models to obtain energies for biomolecular
      modeling. For example, measured partition coefficients, K, are often inserted
      into the formula -RT in K to obtain quantities thought to represent microscopic
      contact interaction free energies. We review evidence here that this procedure
      does not always give microscopically meaningful free energies. Some partitioning
      processes, particularly involving polymeric solvents such as octanol or
      hexadecane, are governed not only by translational entropies and contact
      interactions, but also by free energies resulting from changes in the
      conformations of the polymer chains upon solute insertion. The Flory-Huggins
      theory is more suitable for these situations than is the classical approach. We
      discuss the physical bases for both approaches.

PMID- 9241427
TI  - The structural and functional basis of antibody catalysis.
AB  - Ten years have passed since the initial reports that antibodies could be
      programmed to have enzymatic activity by immunization with a transition-site
      analog. Much of the research over the last decade has focused on defining the
      scope and generality of antibody catalysis; however, during the past two years
      the first few crystal structures of catalytic antibody transition-state analogs
      have been reported. This review analyzes four such structures of catalytic
      antibodies that catalyze markedly different reactions, including ester
      hydrolysis, sulfide oxidation, and a pericyclic rearrangement. Structure-function
      relations for these catalysts are discussed and compared to the structure and
      function of natural enzymes, as well as the chemistry that occurs in solution.

PMID- 9241428
TI  - Advanced EPR spectroscopy on electron transfer processes in photosynthesis and
      biomimetic model systems.
AB  - This review focuses on the recent advances in EPR spectroscopy as they are
      applied both to photoinduced electron transfer in the photosynthetic apparatus
      and to biomimetic systems. The review deals with time-resolved direct-detection
      cw and pulsed EPR and ENDOR methods, both at conventional bands [X-(9.5 GHz), K
      (24 GHz), and Q-(35 GHz)(] and at high frequency bands (W-band, 95 GHz, and even
      higher frequency bands). EPR studies on photosynthetic and model systems in their
      doublet, triplet and radical pair states are surveyed, including their static and
      dynamic properties. APplications of time-resolved EPR in studying photoinduced
      electron and energy transfer in isotropic and anisotropic environments, and the
      concepts of electron spin polarization and magnetic field effects in
      photochemical reactions are also reviewed.

PMID- 9241429
TI  - Use of surface plasmon resonance to probe the equilibrium and dynamic aspects of
      interactions between biological macromolecules.
AB  - Surface plasmon resonance biosensors have become increasingly popular for the
      qualitative and quantitative characterization of the specific binding of a mobile
      reactant to a binding partner immobilized on the sensor surface. This article
      reviews the use of this new technique to measure the binding affinities and the
      kinetic constants of reversible interactions between biological macromolecules.
      Immobilization techniques, the most commonly employed experimental strategies,
      and various analytical approaches are summarized. In recent years, several
      sources of potential artifacts have been identified: immobilization of the
      binding partner, steric hindrance of binding to adjacent binding sites at the
      sensor surface, and finite rate of mass transport of the mobile reactant to the
      sensor surface. Described here is the influence of these artifacts on the
      measured binding kinetics and equilibria, together with suggested control
      experiments.

PMID- 9241430
TI  - Optical detection of single molecules.
AB  - Recent advances in ultrasensitive instrumentation have allowed for the detection,
      identification, and dynamic studies of single molecules in the condensed phase.
      This measurement capability provides a new set of tools for scientists to address
      important current problems and to explore new frontiers in many scientific
      disciplines, such as chemistry, molecular biology, molecular medicine, and
      nanostructured materials. This review focuses on the methodologies and biological
      applications of single-molecule detection based on laser-induced fluorescence.

PMID- 9241431
TI  - Protein folds in the all-beta and all-alpha classes.
AB  - Analysis of the structures in the Protein Databank, released in June 1996, shows
      that the number of different protein folds, i.e. the number of different
      arrangements of major secondary structures and/or chain topologies, is 327. Of
      these folds, approximately 25% belong to the all-alpha class, 20% belong to the
      all-beta class, 30% belong to the alpha/beta class, and 25% belong to the alpha +
      beta class. We describe the types of folds now known for the all-beta and all
      alpha classes, emphasizing those that have been discovered recently. Detailed
      theories for the physical determinants of the structures of most of these folds
      now exist, and these are reviewed.

PMID- 9241432
TI  - Site-specific dynamics in DNA: experiments.
AB  - This chapter reviews the dynamics information obtained from experimental magnetic
      resonance studies of site-specifically labeled duplex DNA. A previous review (43)
      discusses the dynamics of duplex DNA; it develops a theory that shows how
      magnetic resonance experiments are used to detect those dynamics. The methods for
      obtaining information about dynamics as well as a summary of what is now known
      about the site-specific dynamics of DNA are presented. This review contains two
      methods sections which present results using electron paramagnetic resonance and
      nuclear magnetic resonance active probes.

PMID- 9241433
TI  - Isozyme polymorphism of esterases in the genus Lanistes
      (Mollusca:Prosobranchiata) and genetic analysis of populations.
AB  - Esterases from the digestive gland of the snails Lanistes carinatus and Lanistes
      bolteni collected from Egyptian governorates were extracted and analyzed using
      starch gel electrophoresis and five substrates. Twelve esterase bands were
      detected in both Lanistes species. The esterase bands were distributed in three
      main zones, which could be classified as acetylesterases, carboxylesterases, and
      cholinesterases. Depending on the substrates specificity, inhibition properties,
      and relative mobility of esterase bands, the three zones of esterase activity
      could be traced to eight genetic loci. Locality-specific loci were found. Inter-
      and intrapopulation variations are discussed. There is an absence of equilibria
      at all esterase loci in all populations studied, and a high proportion of genetic
      diversity in different esterase loci. The absence of interspecific variations
      proves that Lanistes snails in Egypt belong to one species.

PMID- 9241434
TI  - Tyrosine decarboxylase and dopa decarboxylase in Drosophila virilis under normal
      conditions and heat stress: genetic and physiological aspects.
AB  - The activity of tyrosine decarboxylase (TDC) and dopa decarboxylase (DDC) was
      studied in adults of two lines of Drosophila virilis, contrasting in their
      reaction to stress conditions. Differences were found in the activity of both
      enzymes between individuals of the examined lines. Genetic analysis of these
      differences was made. Each of the two enzymes was found to be controlled by a
      single gene or, possibly, by a block of closely linked genes. The gene
      responsible for TDC activity is located on one of the autosomes (excluding
      chromosome II). DDC activity in D. virilis is regulated by a gene located,
      apparently, on chromosome II. Adults of the line responding to stress by a stress
      reaction (r-line) were shown to react to a short-term heat stress (38 degrees C,
      60 min) by a decrease in TDC activity. TDC activity in flies of the line
      incapable of the stress reaction (nr-line) did not alter in such conditions. DDC
      activity of adults of both lines was found to be unchangeable under stress
      conditions.

PMID- 9241435
TI  - Genetic mapping of a possible new alcohol dehydrogenase sequence to mouse
      chromosome 3 at the Adh-1/Adh-3 complex.
AB  - Southern blot analysis of mouse genomic DNA reveals two EcoRI fragments which
      faintly hybridize to mouse Adh-1 cDNA and are not part of the Adh-1 gene. These
      fragments were isolated from agarose gels, cloned, and characterized. Sequence
      analysis of the 2.1-kb EcoRI fragment suggests that it is likely a pseudogene
      since it does not contain a long open reading frame. However; the 2.0-kb EcoRI
      fragment contains a coding sequence with a long open reading frame which
      corresponds to exon 6 of the mouse Adh-1 gene. Comparison of the coding sequence
      with other known ADHs suggests that the sequence has diverged sufficiently from
      any currently known class of ADH to be a possible distinct class. Further
      confirmation awaits analysis of currently available genomic clones. Using these
      sequences as probe, restriction fragment length polymorphisms were identified for
      each sequence between C57Bl/6J and DBA/2J inbred mouse strains. The strain
      distribution pattern for these allelic differences was determined among the B x D
      recombinant inbred strains. This analysis revealed that the 2.1-kb EcoRI sequence
      is located on chromosome 3 but at a distance from the Adh-1/Adh-3 complex as
      previously reported. However, the new polymorphism identified in the 2.0-kb EcoRI
      fragment enabled this sequence to be mapped at the Adh-1/Adh-3 complex.

PMID- 9241437
TI  - A mutant of Arabidopsis thaliana (L.) Heynh. with modified control of aspartate
      kinase by threonine.
AB  - Mutagenesis and subsequent selection of Arabidopsis thaliana plantlets on a
      growth inhibitory concentration of lysine has led to the isolation of lysine
      resistant mutants. The ability to grown on 2 mM lysine has been used to isolate
      mutants that may contain an aspartate kinase with altered regulatory-feedback
      properties. One of these mutants (RL 4) was characterized by a relative
      enhancement of soluble lysine. The recessive monogenic nuclear transmission of
      the resistance trait was established. It was associated with an aspartate kinase
      less sensitive to feedback inhibition by threonine. Two mutants (RLT 40 and RL 4)
      in Arabidopsis, characterized by an altered regulation of aspartate kinase, were
      crossed to assess the effects of the simultaneous presence of these different
      aspartate kinase forms. A double mutant (RLT40 x RL4) was isolated and
      characterized by two feedback-desensitized isozymes of aspartate kinase to,
      respectively, lysine and threonine but no threonine and/or lysine overproduction
      was observed. Genetical analysis of this unique double aspartate kinase mutant
      indicated that both mutations were located on chromosome 2, but their loci (ak1
      and ak2) were found to be unlinked.

PMID- 9241436
TI  - Isolation and characterization of an unamplified esterase B3 gene from malathion
      resistant Culex tarsalis.
AB  - A malathion-resistant strain of Culex tarsalis has a malathion carboxylesterase
      which rapidly hydrolyzes the insecticide. This is in contrast to organophosphate
      resistant strains of C. quinquefasciatus and C. pipiens, which have elevated
      levels of general B esterases due to amplification of the corresponding genes,
      producing increased amounts of enzyme which appear to protect the insects by
      sequestering the insecticide. The contribution to resistance of the homologous
      esterase B3 (Est beta 3) gene (est beta 3) in C. tarsalis was investigated by
      cloning and characterizing sequences from resistant and susceptible strains. est
      beta 3 is similar to est beta 1, both structurally and in sequence. The first
      intron of est beta 3, however, has a region of extensive repeats which may be
      responsible for the inefficient processing of the transcript. Southern blots
      indicate that the gene is single copy in both strains, and northern blots show
      that it is not greatly overexpressed in the resistant insects. est beta 3 cDNAs
      from resistant and susceptible strains have 98% amino acid identity. It appears
      that, in contrast to other studies, est beta 3 does not play a significant role
      in insecticide resistance in our strains of C. tarsalis, and the molecular
      responses of pest insects to organophosphates may be more diverse than has been
      suggested.

PMID- 9241438
TI  - Potassium channel opener reduces extracellular glutamate concentration in rat
      focal cerebral ischemia.
AB  - The vasodilatory action of potassium channel openers through a membrane
      hyperpolarizing action is well known, but little is known about the effect of
      these drugs on ischemia-induced glutamate release in the brain. We evaluated the
      effects of a potassium channel opener (Y-26763), given intravenously at 0.03
      mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood
      flow, extracellular glutamate concentration, and infarct volume in rats with
      focal ischemia. Y-26763 significantly inhibited the increase in extracellular
      glutamate concentration at 50 and 60 min of ischemia with a significant reduction
      of mean arterial blood pressure. However, there was no significant difference in
      blood flow in the core of infarcted cortex or in infarct volume between Y-26763-
      and vehicle-treated groups. These results suggest that Y-26763 inhibited
      presynaptic glutamate release through hyperpolarizing the membrane, but infarct
      volume was not reduced because of insufficient perfusion owing to its hypotensive
      effect.

PMID- 9241439
TI  - Calbindin immunoreactivity delineates the circadian visual centers of the brain
      of the common marmoset (Callithrix jacchus).
AB  - The hypothalamic suprachiasmatic nucleus and the thalamic pregeniculate nucleus
      (which includes the intergeniculate leaflet) comprise the circadian visual system
      in the primate brain. In this study, we used intraocular injections of cholera
      toxin subunit B to identify those nuclei in the common marmoset brain, and
      demonstrated that calbindin D-28k immunoreactivity apparently labels most neurons
      in both the suprachiasmatic and pregeniculate nuclei. These data suggest that
      calbindin D-28k could represent a reliable neuronal marker for structures of the
      circadian visual system in marmosets and provide anatomical information on the
      primate equivalent of the rodent intergeniculate leaflet.

PMID- 9241440
TI  - Increased levels of mRNA for beta- but not alpha-subunit of calmodulin kinase II
      following kindled seizures.
AB  - We studied levels of mRNA for the alpha- and beta-subunits of calmodulin (CaM)
      kinase II using the amygdaloid kindling model of epilepsy. There were significant
      increases in mRNA for the beta-subunit of CaM kinase II in the hippocampus 4-24 h
      after stage 5-kindled seizures. Moreover, this mRNA was significantly increased
      by 20.0-26.5% in the bilateral dentate gyrus 8 to 24 h after kindled seizures.
      The beta-subunit mRNA was also significantly increased by 13.5-19.0% in the CA3
      on the side ipsilateral to the stimulation, 4 to 8 h after kindled seizures. mRNA
      for the alpha-subunit of CaM kinase II was not significantly changed in the
      regions examined for up to 24 h after the kindled seizures. These results suggest
      that CaM kinase II mediates the molecular processes that follow kindled seizures.
      It is possible that increases in CaM kinase II-dependent protein phosphorylation
      are associated with the plastic changes in kindling.

PMID- 9241441
TI  - Effects of combined ventral forebrain grafts to neocortex and amygdala on
      behavior of rats with damage to the nucleus basalis magnocellularis.
AB  - In rats with damage to the nucleus basalis magnocellularis, transplantation of
      the embryonic ventral forebrain to the neocortex improves behavioral performance
      in some behavioral tasks. The present investigation focuses on improvement of
      behavioral performance by combined graft placement to both neocortex and
      amygdala. Male rats received unilateral microinjections of quisqualate to the
      nucleus basalis magnocellularis to produce cell damage. Embryonic ventral
      forebrain cell suspensions were placed in one group of rats in the frontal and
      parietal neocortex, in a second group in the amygdala, and in a third group in
      the frontal and parietal neocortex and in the amygdala. These groups were
      compared to a group of nonoperated rats and a group of rats with damage but with
      no grafts. Quisqualate-induced damage to the nucleus basalis magnocellularis
      reduced cholinergic innervation in the ipsilateral cortical hemisphere, impaired
      performance in the one-trial training version of passive avoidance, an increased
      motility and time spent in the open arms of the elevated plus maze. Combined
      graft placement to neocortex and amygdala normalized performance of passive
      avoidance and restored the normal time spent in the open arms of an elevated plus
      maze. These results suggest that after damage to the nucleus basalis
      magnocellularis, modulation of function in multiple brain regions may be
      necessary for optimization of adaptive behavior in situations involving induction
      of fear.

PMID- 9241442
TI  - AMPA neurotoxicity in cultured cerebellar granule neurons: mode of cell death.
AB  - Various forms of cell death induced by the glutamate receptor agonist, alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), were analyzed by
      determining the capacity of cultured cerebellar granule cells to metabolize 3
      [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) into formazan,
      by measuring the leakage of lactate dehydrogenase (LDH), by using confocal
      microscopy to visualize propidium iodide staining of apoptotic nuclei, and by
      using field inversion gel electrophoresis (FIGE) for the detection of AMPA
      produced cleavage of DNA into high molecular-weight fragments (50 kbp). All these
      measures indicated that stimulation of AMPA receptors may be involved in the
      neurotoxic effects of glutamate, and that AMPA-induced neurotoxicity in
      cerebellar granule cells display morphologically distinct features of both
      necrotic and apoptotic modes of cell death. In agreement with previous
      observations, a blockade of AMPA receptor desensitization was necessary to unmask
      AMPA-induced functional responses in cultured cerebellar granule neurons in
      vitro. Microfluorimetric measurements of free cytoplasmic calcium concentrations
      ([Ca2+]i) in single cerebellar neurons revealed that AMPA neurotoxicity was
      accompanied by a pronounced elevation of [Ca2+]i. Our current results add further
      evidence to the notion that glutamate-induced neurotoxicity in cerebellar granule
      cells is mediated not only through NMDA receptors but also through a direct
      activation of AMPA receptor-regulated cation channels.

PMID- 9241443
TI  - Synergism of 5-HT 1B/D antagonists with paroxetine on serotonin efflux in rat
      ventral lateral geniculate nucleus slices.
AB  - Serotonin (5-HT) efflux in rat ventral lateral geniculate nucleus (vLGN) slices
      was evoked by electrical stimulation (20 pulses at 100 Hz, 10 mA, 190 ms train)
      and measured, along with 5-HT uptake, by fast cyclic voltammetry at implanted
      carbon fibre microelectrodes. Paroxetine (100 nM), a selective serotonin reuptake
      inhibitor (SSRI), increased stimulated 5-HT efflux to 194 +/- 25% of pre-drug
      values at maximum (mean +/- SEM, n = 5) and the half-life of uptake to 684 +/-
      135%. When given alone, neither the selective 5-HT 1B antagonist isamoltane (1
      microM) nor the 5-HT 1D/B antagonist GR 127935 (50 nM), affected 5-HT efflux or
      uptake under this stimulation paradigm. When added in combination with
      paroxetine, both isamoltane and GR 127935 significantly potentiated the effect of
      paroxetine on stimulated 5-HT efflux: isamoltane to 302 +/- 48% at maximum (p <
      0.05 vs. paroxetine alone), GR 127935 to 318 +/- 95% (p < 0.05 vs. paroxetine
      alone) of pre-drug values. Neither isamoltane nor GR 127935 had any effect on 5
      HT uptake. The selective 5-HT 1A antagonist WAY 100635 (10 nM) had no effect on 5
      HT efflux or uptake, alone or in combination with paroxetine. These data suggest
      that, under these experimental conditions, paroxetine gives rise to tonic
      activation of the vLGN terminal 5-HT autoreceptors. Furthermore, these data show
      that 5-HT 1B and possibly 5-HT 1D antagonists block this inhibitory autoreceptor
      tone and may thus be a useful addition to SSRI treatment in the clinic.

PMID- 9241444
TI  - Influence of gender and gonadectomy on bicuculline-induced convulsions and on
      GABAA receptors.
AB  - The response to IV administration of GABAA receptor antagonist bicuculline was
      studied in young (30 days) and in adult gonad-intact or gonadectomized male and
      female rats. The properties of GABAA receptors, obtained from cortex and
      cerebellum 30 days following gonadectomy, and the affinity of muscimol and
      bicuculline for cortical and cerebellar GABA binding sites were also studied.
      While young rats failed to show sex differences, the threshold doses of
      bicuculline producing the first myoclonic twitch and running/bouncing clonus (RB
      clonus) were lower in adult male than female rats. Fifteen days after gonadectomy
      or sham operation male rats needed less bicuculline to the onset of myoclonic
      twitch and RB clonus than identically treated females, while orchidectomized rats
      needed more bicuculline to the onset of tonic hindlimb extension than all other
      groups examined. All sex differences disappeared 30 days following gonadectomy.
      At the same time, in males gonadectomy decreased the affinity and enhanced the
      density of cortical 3H-muscimol binding sites. In female rats, gonadectomy only
      decreased the affinity of cortical GABAA receptors. Only regional but not sex
      differences were observed in the affinity of muscimol and bicuculline for GABAA
      receptors. Sex differences in the threshold doses of bicuculline-producing
      convulsions do not correlate either with the properties of cortical and
      cerebellar GABAA receptors or with the affinity of bicuculline for the same
      binding sites.

PMID- 9241445
TI  - Dopaminergic innervation of the monkey caudal nucleus accumbens.
AB  - Previous studies have shown that the monkey (Macaca fuscata) caudal nucleus
      accumbens is neurochemically subdivided into three subdivisions, the medial,
      dorsolateral, and ventral subdivisions. In this study, dopaminergic innervation
      of these three subdivisions was studied in detail for the first time by light
      microscopic immunocytochemistry using a monoclonal antibody against dopamine. The
      patterns of dopamine fiber distribution were heterogeneous even within each
      subdivision. The medial subdivision showed extremely dense accumulation of thick
      dopamine-immunoreactive varicose fibers. Some areas with densely packed cells in
      Nissl-stained sections corresponded to dopamine-poor areas, while another area
      with concentrated cells corresponded to a dopamine-rich area. There were also
      areas with sparse cells that contained a few dopamine-immunoreactive fibers. In
      the dorsolateral subdivision thick dopamine-immunoreactive varicose fibers were
      found sparsely among diffuse puncta. The ventral subdivision exhibited similar
      profiles to those in the dorsolateral one, and there were also many
      characteristic spiral dopamine-immunoreactive fibers of passage. The present
      study indicates that the dopaminergic structures of the monkey nucleus accumbens
      differ according to the subterritories, and are morphologically different from
      those in the caudate-putamen.

PMID- 9241446
TI  - Mapping of cortical metabolic activation in soman-induced convulsions in rats.
AB  - The metabolic activation of the cerebral cortex during convulsions induced by the
      organophosphorus cholinesterase inhibitor soman was studied in detail. Soman was
      given at a dose equivalent to 0.9 LD50 (100 microgram/kg SC after pretreatment
      with 26 microgram/kg pyridostigmine, IM, to decrease lethality) to examine
      separately the metabolic effects of severe acetylcholinesterase inhibition,
      present always with this dose, and convulsions, present only in some of the
      animals. Cerebral glucose utilization (CGU) values of cortex divided by CGU of
      brain stem (nCGU) were calculated for 96 locations in nine coronal slices.
      Animals injected with pyridostigmine-soman and that developed convulsions (n = 7)
      showed statistically significant increases of nCGU with regard to animals
      injected with saline (n = 5) in 33 locations, 27 of which were in a single
      cluster, with the piriform cortex at its center. Perirhinal cortex, and insular
      cortex also showed significantly higher nCGU in convulsing rats. Other foci of
      elevated nCGU were found in frontal and parietal locations. In animals injected
      with pyridostigmine-soman and that did not develop convulsions (n = 5) in spite
      of severe cholinesterase inhibition, a single location (piriform cortex) showed
      significantly higher nCGU than controls. Neuropathology evaluation showed a
      significant decrease in viable cells only in animals that developed convulsions.
      This effect correlated with enhanced nCGU. It is concluded that the presence of
      convulsions, and not exposure to pyridostigmine-soman, determined the pattern of
      nCGU cortical activation, which correlated closely with the structural changes.

PMID- 9241447
TI  - Effect of pertussis toxin injected into the ventral tegmental area on amphetamine
      induced Fos protein in the nucleus accumbens.
AB  - Amphetamine produces an enhanced locomotor stimulatory response in animals
      injected with pertussis toxin into the ventral tegmental area. This response is
      dependent on the activation of D1 receptors in the nucleus accumbens. The
      immediate early gene, c-Fos, has been used as a cellular marker for increases in
      dopamine neurotransmission in the nucleus accumbens. The purpose of the present
      study was to determine whether the administration of pertussis toxin into the
      ventral tegmental area results in an increased ability of amphetamine to induce
      Fos-positive immunoreactivity in the nucleus accumbens. Amphetamine (1 mg/kg and
      2 mg/kg IP) produced a greater number of Fos-positive cells in the nucleus
      accumbens of pertussis toxin-treated animals as compared to vehicle-treated
      controls. However, the increase in Fos immunoreactivity at the higher amphetamine
      dose was not associated with a corresponding increase in locomotor activity.
      These data suggest that amphetamine produces an enhanced increase in dopamine
      neurotransmission in the nucleus accumbens of pertussis toxin-treated animals,
      resulting in an increased induction of Fos-related antigens.

PMID- 9241448
TI  - Reform of well-baby services.

PMID- 9241449
TI  - Canadian immunization cuts will cause child deaths.

PMID- 9241450
TI  - Treating dermatitis artefacta.

PMID- 9241451
TI  - Referral for psychosocial assessment.

PMID- 9241452
TI  - The art of medicine.

PMID- 9241453
TI  - Response to thoughts on the importance of being different.

PMID- 9241454
TI  - Pharmacotherapy debate on alcohol withdrawal syndrome.

PMID- 9241455
TI  - Neonatal hair test for cocaine. Toronto experience.

PMID- 9241456
TI  - Ophthaproblem. Angioid streaks.

PMID- 9241457
TI  - Dermacase. Hereditary palmoplantar keratoderma.

PMID- 9241458
TI  - Improving technique of performing circumcisions with a gomco clamp.

PMID- 9241459
TI  - Use of digoxin in heart failure. Should we bother?

PMID- 9241461
TI  - Where do children go? Comparing the after-hours availability of family physicians
      and primary care pediatricians in four Canadian cities.
AB  - OBJECTIVE: To describe and compare family physicians' and pediatricians' after
      hours availability for pediatric care in four Canadian cities. DESIGN: Cross
      sectional telephone survey. SETTING: Winnipeg, Toronto, Ottawa, and Montreal
      pediatric and family practices. PARTICIPANTS: All primary care pediatricians and
      an equal number of family physicians randomly selected from the membership list
      of the College of Family Physicians of Canada were matched by postal code. Sixty
      four (10%) of 282 family physicians and 296 primary care pediatricians were
      excluded, most because no office telephone number was found. MAIN OUTCOME
      MEASURES: "After hours" was defined as between 1800 and 0700 hours on weekdays
      and 0900 to 2400 hours on weekend days. Outcomes included demographics, year of
      graduation, day of call, time of call, and availability of physician. RESULTS:
      Availability varied markedly by city rather than by physicians were available
      after hours: 92.4% in Winnipeg, 56.0% in Toronto, 65.5% in Ottawa, and 26.9% in
      Montreal. Winnipeg, Toronto, and Montreal showed no significant differences
      between specialties in availability. Only Ottawa pediatricians were significantly
      more available than family physicians when age was taken into account (adjusted
      relative risk = 2.17, 95% confidence interval = 1.51 to 3.12). Stratified
      analysis showed no differences by day of call, time of call, or physicians' sex.
      Physicians graduating before 1975 in both groups tended to be more available in
      all cities than younger physicians. CONCLUSIONS: Regional differences appear to
      influence after-hours availability more than specialty. Older physicians from
      both groups were more available than younger physicians.

PMID- 9241460
TI  - Can we predict which patients with community-acquired pneumonia we can keep out
      of hospital?

PMID- 9241462
TI  - Neonatal male circumcision after delisting in Ontario. Survey of new parents.
AB  - OBJECTIVE: To determine the prevalence of neonatal circumcision immediately
      following delisting of the procedure in Ontario and to examine parents'
      knowledge, attitudes, and behaviours regarding circumcision. DESIGN: Cross
      sectional survey. SETTING: Perinatal tertiary care centre in southwestern
      Ontario. PARTICIPANTS: Of the 151 mothers approached, three were excluded because
      they did not speak English and two declined participation; 112 of 146 mothers of
      healthy male newborns responded for a response rate of 77%. MAIN OUTCOME
      MEASURES: Circumcision status of infant and parents' knowledge, attitudes, and
      behaviour. RESULTS: The circumcision rate before delisting had been 56.2%; in the
      months immediately after, the rate was 59.8% (95% confidence interval was 51%,
      69%). Mothers of infants in the outcome groups did not differ significantly in
      any demographic feature other than education, where the group deciding against
      circumcision reported higher education levels (Wilcoxon nonparametic two-sample
      test: zeta = 2.29, P = 0.02). Mothers who chose circumcision listed medical (59%)
      and sociocultural considerations (40%) a most important to their decision.
      Father's circumcision status was strongly associated with the infant's (chi 2[df
      1] = 25.13, P = 0.0001). Although 74% discussed circumcision with their family
      physicians, many parents were not well informed about risks or benefits.
      Anesthetic use during circumcision was reported by 29%, but 48% did not know
      whether any had been used. CONCLUSIONS: The prevalence of neonatal circumcision
      did not change after delisting. Informed consent was often lacking. Sociocultural
      issues are important to some parents and need to be addressed in the consultation
      process.

PMID- 9241464
TI  - Faculty advisor program for family medicine residents.
AB  - PROBLEM BEING ADDRESSED: In response to the accreditation guidelines of the
      College of Family Physicians of Canada's (CFPC) Task Force on Intraining
      Evaluation, the Department of Family Medicine at McGill University implemented a
      faculty advisor program on July 1, 1993. OBJECTIVE OF PROGRAM: In addition to
      meeting the requirements of the CFPC, the faculty advisor program was developed
      to foster communication between residents and faculty, increase opportunities for
      feedback, promote self-directed learning, and personalize the educational
      experience of trainees. MAIN COMPONENTS OF PROGRAM: Residents were assigned an
      advisor. They were expected to meet their advisors monthly to discuss educational
      objectives, performance, career planning, and any problems. Educational plans
      were to be completed at each meeting. CONCLUSIONS: Feedback from advisors and
      residents has been positive, with both groups expressing overall satisfaction
      with the program. The faculty advisor program will continue but will be modified
      to address problems identified and better meet the needs of faculty and
      residents.

PMID- 9241465
TI  - Attention-deficit hyperactivity disorder (ADHD) and frontal-motor cortex
      disconnection.
AB  - Attention-Deficit Hyperactivity Disorder (ADHD) is a very common pediatric
      neuropsychiatric entity of still unknown etiology, and is thus a topic of
      controversy. A neurological concept is presented in order to attain a better
      conceptualization of ADHD. This concept focuses on the frontal lobe as the
      inhibitor of excessive motor activity. This inhibitory function is presumed to be
      most active during childhood. The concept of a disturbed frontal-motor cortex
      connection was first developed in view of a completely different and rare
      disorder of childhood: Rett Syndrome (RS) with smallness of the frontal lobe,
      excessive motor activity and EEG abnormalities often confined to the Rolandic
      region. Accordingly, what is due to structural damage in RS, might be caused by
      simple dysfunction in ADHD under essential ly benign circumstances. Not a damaged
      but a "lazy" frontal lobe results in disinhibited motor activity and also in
      disturbed attention ( a predominantly frontal lobe function). In the light of
      this concept, the calming effect of methylphenidate in ADHD is quite logical
      (frontal stimulation improving motor inhibition) and not paradoxical. It is the
      "lazy" frontal lobe that responds to "the whip" whereas a truly sick frontal lobe
      as in RS would be unable to respond.

PMID- 9241463
TI  - Strategies for diagnosing and managing medication-induced headache.
AB  - PROBLEM ADDRESSED: Headache is a common clinical disorder. Nearly 50% of patients
      with headaches use prescription medications, and 90% regularly use
      nonprescription drugs. Medication-induced headaches (MIH) are chronic daily
      headaches caused by overuse of medicine. OBJECTIVES: To summarize the diagnostic
      criteria for MIH, to determine the investigations necessary to confirm the
      diagnosis and exclude other possible diagnoses, and to establish recommendations
      for managing MIH. MAIN FINDINGS: Diagnosis of MIH is based on patient's history
      and the clinical characteristics of the headache. Treatment includes patient
      education and support, withdrawal of offending medications, relief of withdrawal
      symptoms, and specific treatment of residual headache. When migraine and other
      causes of headache are adequately addressed, patients will not seek additional
      pain relief. CONCLUSION: Medication-induced headache is preventable. The key to
      prevention is appropriate drug therapy to relieve the primary headache. All
      patients with MIH can be treated and most cured.

PMID- 9241466
TI  - Visual evoked responses in Alzheimer's disease: a review.
AB  - This review of the literature has shown that a delayed flash P2, in the presence
      of a normal flash P1 and pattern-reversal P100, can distinguish groups of
      Alzheimer's patients from groups who are healthy, psychiatrically ill, or
      suffering from other types of dementia. The VER's usefulness in the individual
      patient remains undetermined. With today's techniques, too many patients are
      misclassified. False negatives may result if Alzheimer's patients with visual
      symptoms are a distinct subgroup. Those with a normal flash VER may have cortical
      dysfunction outside the visual association areas. This would most likely be in
      the earliest stages of the disease before the atrophy becomes widespread. It may
      be that a VER test would only be valid in established disease. Future research
      should use adequate numbers of patients who are in a single category of mild,
      moderate or severe, so that the applicability of a VER test in the early stages
      of the disease can be determined. Strict diagnostic criteria such as the NINCDS
      ADRDA guidelines should be used. Patients should be drug free, or at least not
      taking medications with anticholinergic properties. Flash VER should be obtained
      using a strobe light with eyes closed, and the pattern VER using a black and
      white television with a large pattern and high contrast.

PMID- 9241467
TI  - Visual electrophysiology in Parkinson's disease: PERG, VEP and visual P300.
AB  - A retinal dopaminergic deficiency underlies some visual changes in Parkinson's
      disease (PD), in particular those elicited by stimuli near the peak of the human
      and monkey spatial contrast sensitivity. The correspondence of retinal changes
      and VEP alterations is not perfect: they do not seem to rely on identical
      mechanisms. It seems that additional pathology beyond the retina affects visual
      responses, including VEPs. The relevance of "distal" primary VEP changes to
      higher cognitive visual abnormalities in PD is not established at present.

PMID- 9241468
TI  - Auditory event-related potentials and statistical probability mapping in
      obsessive-compulsive disorder.
AB  - The current exploratory investigation was undertaken to replicate and extend
      previous findings of auditory event related potentials (ERPs) observed in
      obsessive-compulsive disorder (OCD). Similar to previous ERP studies, this study
      revealed a decreased slow wave (SW) (post P300) latency, a trend towards
      decreased P300 latency and a greater N200 amplitude in OCD subjects than in
      controls. In addition, the chronicity of OCD symptoms was correlated with the 140
      170 millisecond integrated amplitude and the severity of OCD symptoms correlated
      with the 386-438 millisecond integrated amplitude. Current findings lend
      additional support to evidence suggesting OCD represents, in part, hyperarousal
      of the cortex.

PMID- 9241469
TI  - Decreased multi-band posterior interhemispheric coherence with a lipoma on the
      corpus callosum: a case report of a possible association.
AB  - The corpus callosum plays a role in mediating interhemisphere communication.
      Coherence may be a quantitative EEG-based measure of this communication. The
      present report is of a female schizophrenic patient with a marked coherence
      deficit in the temporal-parietal-occipital region involving multiple frequency
      bands. An MRI scan of her brain revealed a lipoma involving the splenium of the
      corpus callosum. It is speculated that this lipoma may have caused a physical
      impingment on or developmental aberration of adjacent callosal fibers, resulting
      in the observed coherence deficit. Further studies of coherence measures in
      patients with collosal lipomas are proposed.

PMID- 9241470
TI  - Quantitative EEG correlates of normal aging in the elderly.
AB  - To clarify the effect of normal aging on the EEG in the elderly, relative EEG
      power and coherence were studied in 68 elderly subjects (age range 61-90 years)
      as well as in 20 young subjects (age range 23-38 years). Relative beta power was
      significantly higher in the elderly subjects, while no significant differences
      were seen among the elderly groups. Therefore it may be assumed that EEG power in
      the centrooccipital region among the normal elderly remains almost unchanged.
      Also, age had no effect on interhemispheric coherence. However, intrahemispheric
      coherence was found to decrease with age in all bands almost linearly. Thus,
      intrahemispheric coherence is a more sensitive indicator of normal aging than
      relative power.

PMID- 9241471
TI  - Frontal lobe epilepsy with secondarily generalized 3 Hz spike-waves: a case
      report.
AB  - We report a case of frontal lobe epilepsy with bursts of 3 Hz spike-wave, often
      dominant in the left frontal lobe, that sometimes developed into a secondary
      bilateral generalization. This patient was a 69-year-old male with a history of
      epileptic seizures that began 3 months following a head injury at the age of 17.
      His seizures occurred two or three times a day, but after medication the
      frequency was halved. The seizures began with a feeling of heaviness of the head,
      accompanied by myoclonus at both angles of the mouth. Consciousness was clear for
      most of the seizures, which ranged from several seconds to many minutes. When
      seizures lasted for longer than 10 minutes, a temporary generalization
      accompanied by a loss of consciousness was sometimes observed. Neurological tests
      and cranial MRI yielded no abnormal local findings. The secondary generalized
      seizure seen in this case is the so called "secondary bilateral synchrony (SBS)."
      We succeeded in making an EEG recording of the bilateral generalization of a
      seizure discharge originating in the left frontal lobe, which until now has not
      been done. This case is direct proof that a primary frontal focus can give rise
      to SBS.

PMID- 9241472
TI  - Studies on quantitative beta activity in EEG background changes produced by
      intravenous diazepam in epilepsy.
AB  - This article deals with the further systematic investigation of the effects of
      diazepam on quantitative beta activity in EEG background activity, and the
      determination of the affecting factors concerned. Diazepam (0.1-0.03 mg/kg) was
      injected intravenously, the percentage of diazepam-induced changes in beta
      activity (PDICB) over the 8 sites of scalp EEG recordings was quantitatively
      analyzed using spectral analysis. The affecting factors concerned were also
      explored by univariate and multivariate statistical analysis in 84 cases of
      epilepsy. The results showed that the mean PDICB value in epileptic patients
      (4.49 +/- 4.51) was significantly lower than that in normal controls (8.03 +/-
      5.55). In patients with slowing of EEG background pre-diazepam, AED treatment,
      long duration of receiving AEDs, refractory epilepsy and brain structural damage,
      the PDICB value was statistically significantly reduced. The mean PDICB values
      were lower in the patients with CPS, GTCS, etiologic factors, or paroxysmal
      discharges on the pre-drug EEG recordings, and the PDICB tended toward decrease
      with advancing disease duration and seizure frequency; however, these trends did
      not reach statistical significance. Besides the PDICB values also did not
      statistically correlate with sex, age and age at seizure onset. In multi-variate
      analysis with a stepwise regression model, it was found that slowing of EEG
      background and AED treatment were independently and negatively associated with
      the decreased PDICB. These results suggest that a reduction of beta activity
      induced by diazepam, which may involve the whole brain besides the epileptogenic
      lesion, is significantly related not only to cerebral function impairment of
      structural changes due to the epileptic process, but also to AED interactions or
      synergistic effects.

PMID- 9241473
TI  - Measurement of P300 and sleep characteristics in patients with hypersomnia: do
      P300 latencies, P300 amplitudes, and multiple sleep latency and maintenance of
      wakefulness tests measure different factors?
AB  - To explore further the relationship between ease of falling asleep, ability to
      maintain wakefulness, attention and information processing in sleep apnea and
      other sleep disorders, we conducted a thorough analysis of the similarities,
      differences and correlations between auditory and visual P300 amplitudes and
      latencies, and tests of sleepiness. The 283 consecutive patients presenting with
      hypersomnia were administered nocturnal polysomnography. Next day they underwent
      auditory and visual P300 recordings, Multiple Sleep Latency Test (MSLT) and
      Maintenance of Wakefulness Test (MWT). Correlation coefficients were calculated
      between auditory and visual P300 amplitudes and latencies, respiratory
      disturbance index (RDI), sleep efficiency, % stage 1, and the tests for
      sleepiness. Factor analysis was performed with data from P300 testing, MSLT and
      MWT. Auditory P300 amplitude was correlated with sleep efficiency. Auditory P300
      latency was correlated with % stage 1, RDI, MSLT and MWT. Visual P300 latency was
      correlated with % stage 1, sleep efficiency and MWT. MSLT but not MWT was
      negatively correlated with sleep efficiency. Factor analysis suggests three
      factors: attention, information processing, and sleepiness. We conclude that P300
      latencies and tests of sleepiness (MSLT and MWT) measure different abilities in
      patients with diagnosable disorders of daytime sleepiness.

PMID- 9241474
TI  - "Back to the kitchen".

PMID- 9241475
TI  - Toward a pathophysiology of attention-deficit/hyperactivity disorder.
AB  - Converging insights into attention-deficit/hyperactivity disorder (ADHD) support
      the notion that ADHD is best characterized behaviorally as a disorder of self
      regulation or executive functioning. Anatomic neuroimaging studies suggest that
      the relevant regulatory circuits include the prefrontal cortex and the basal
      ganglia, which are modulated by dopaminergic innervation from the midbrain and by
      stimulant medications. The emerging model proposed in this review encompasses a
      developmental perspective into this common condition.

PMID- 9241476
TI  - Laboratory predictors of fluid deficit in acutely dehydrated children.
AB  - To determine which laboratory studies are most predictive of the fluid deficit in
      acutely dehydrated children, we studied a convenience sample of 40 children
      requiring intravenous fluid resuscitation. Nine laboratory studies (serum BUN/cr,
      total serum CO2, serum uric acid, serum anion gap, urine anion gap, venous pH,
      venous base deficit, urine specific gravity, and fractional excretion of sodium)
      were individually assessed in simple linear regression models with fluid deficit
      as the dependent variable. Only the serum BUN/cr and serum uric acid were
      significantly associated with increasing fluid deficit (r = 0.52, P = 0.0005 and
      r = 0.35, P = 0.03, respectively). The sensitivities and specificities of these
      two laboratory studies for the detection of > 5% fluid deficit were poor.
      Conventional laboratory studies used to assess dehydration in children are poorly
      predictive of fluid deficits.

PMID- 9241477
TI  - Fluid and electrolyte therapy.

PMID- 9241478
TI  - Nontuberculous mycobacterial cervical adenitis.
AB  - Granulomatous inflammation is a common finding in pathologic evaluation of
      surgically excised chronic lymphadenopathy in children. Confusion exists
      regarding diagnosis and management of these lesions. Over a 10-year period at The
      Children's Hospital of Philadelphia, a total of 81 children were identified with
      biopsy-confirmed granulomatous lesions of the head and neck, with nontuberculous
      mycobacteria (NTM) accounting for 67 of the cases. The typical presentation was
      that of a nontender mass in the cervicofacial area present for weeks to months,
      unresponsive to antimicrobials. All underwent surgical excision, which was
      curative in 54 patients; 13 children required additional procedures. This paper
      reviews NTM, its typical clinical presentation, difficulty in diagnosis, and the
      methods of treatment.

PMID- 9241479
TI  - Congenital malaria: an African survey.
AB  - Even in malaria-endemic areas, congenital malaria has been considered to be rare.
      Some recent reports suggest, however, that up to one fourth of newborns in some
      areas may be parasitemic. In an effort to determine current prevalence rates of
      congenital malaria, malaria smears were done on peripheral blood from 100
      peripartum mothers and on cord blood from their offspring at each of seven sites
      spanning sub-Saharan Africa. The prevalence rate of maternal parasitemia was 15%
      overall and varied from 4% to 30% at the different sites. Congenital malarial
      infection was found in 7% of newborns, the prevalence rate varying from 0% to 23%
      at the different sites. There was no apparent relationship between the season of
      sampling and either the prevalence rates of parasitemia or the penetrance of
      malaria from mother to offspring. In summary, congenital malarial infection is
      not rare in sub-Saharan Africa, but the prevalence rate of neonatal parasitemia
      varies from site to site.

PMID- 9241480
TI  - Bodyfat analysis and perception of body image.
AB  - Obesity is a common nutritional problem among children. Using the Futrex 5000A
      method of bodyfat measurement, this prospective study determined the percentage
      bodyfat in a self-selected, indigent, predominantly black population and the
      accuracy of perceived body image. Bodyfat exceeded the optimal range in 39% and
      67% of female and male children, respectively. Females tended to view themselves
      as fatter and males perceived themselves as thinner than their actual
      composition. Parents were more accurate in their perception of obesity in their
      daughters (88%) than in their sons (52%). Children did not recognize the
      importance of exercise in preventing obesity. Bodyfat measurement and counseling
      should be done at an early age to improve this remarkable lack of perception
      about obesity.

PMID- 9241481
TI  - Polymicrobial bacteremia: a presentation of Munchausen syndrome by proxy.

PMID- 9241482
TI  - Pigmented villonodular synovitis of the wrist in childhood.

PMID- 9241483
TI  - Miniature disc battery in the nose: a dangerous foreign body.

PMID- 9241484
TI  - Activation of prophenoloxidase in the plasma and haemocytes of the marine mussel
      Perna viridis Linnaeus.
AB  - Phenoloxidase activity was detected in plasma and haemocytes of the marine mussel
      Perna viridis. This enzyme exists as a proenzyme, prophenoloxidase (proPO), in
      both these haemolymph fractions and could be activated in vitro by exogenous
      proteases (trypsin and alpha-chymotrypsin) and a detergent (sodium dodecyl
      sulphate). In addition, laminarin (a polymer of beta-1,3 glucan) and bacterial
      lipopolysaccharides (LPSa) effectively triggered proPO activation in these
      haemolymph fractions. The activation of proPO by non-self molecules was dependent
      upon calcium ions at a low concentration. This activation process appeared to
      involve a limited proteolysis, since serine protease inhibitors (soybean trypsin
      inhibitor, benzamidine or p-nitrophenyl-p'-guanidinobenzoate) suppressed
      conversion of proPO to the active enzyme. This study demonstrates the selective
      response of plasma and haemocytic proPO to activation by different types of
      bacterial LPS tested and suggests that proPO system in both plasma and haemocytes
      of P. viridis serves an important function in non-self recognition and host
      immune reactions.

PMID- 9241485
TI  - MHC class II B genes in the channel catfish (Ictalurus punctatus).
AB  - Two different cDNA sequences for major histocompatibility complex (MHC) class II
      beta chains from the channel catfish (Ictalurus punctatus) have been identified.
      Homology between these sequences and those previously identified as MHC class II
      B genes in other teleosts suggests they represent alleles of the DAB locus. The
      inferred amino acid sequences show strong evidence for a functional polypeptide
      chain with a peptide binding region. Southern blot analysis reveals polymorphism
      in the MHC class II B gene(s) of the channel catfish and suggests the presence of
      two to four genes.

PMID- 9241486
TI  - Two modes of tunic cuticle formation in a colonial ascidian Aplidium yamazii,
      responding to wounding.
AB  - The defensive responses in ascidian tunic were investigated in a colonial
      ascidian Aplidium yamazii by means of light- and electron-microscopy with special
      reference to the cuticle formation (restoration) of the tunic. When the tunic was
      wounded by cutting with a razor blade, the tunic around the wounds shrank to
      close the wound, and electron-dense fibers appeared and covered the exposed
      surface of the wound. The tunic shrinkage is probably promoted by the contraction
      of the cellular network in the tunic. On the other hand, when a part of the tunic
      was damaged by the injection of distilled water or 5% NaOH, a cuticular boundary
      appeared in the tunic, separating the damaged and undamaged tunic. Before the
      completion of the boundary formation, tunic cells gather around the boundary
      precursor that is formed from the electron-dense fibers. Thus, there are two
      different modes of defensive response involving cuticle formation in A. yamazii.
      Although the regulatory mechanism is still uncertain, one or other of the modes
      should be elicited in response to many damaging stimuli.

PMID- 9241487
TI  - Characterization of a T cell lineage marker in carp (Cyprinus carpio L.).
AB  - A monoclonal antibody against thymocytes (WCL9; of IgG1 class) was produced by
      immunization of mice with isolated membrane molecules of carp thymocytes. Flow
      cytometric and fluorescence microscopic analysis showed that WCL9 was reactive
      with 30-50% of thymocytes and not with lymphoid cells from blood, pronephros,
      spleen and intestine. Cryo-sections of thymus showed a WCL9+ and WCL9- region in
      3-month-old fish and only WCL9+ cells in 1-week-old fish. Because the WCL9-
      region is more medulla-like, the WCL9+ cells can be considered as cortical
      thymocytes. The majority of WCL9+ thymocytes appeared to have a higher density
      (1.06-1.07 g/mL) than the WCL9- cells (1.02-1.06 g/mL). Immunogold labelling or
      comparison of both density fractions did not show clear ultrastructural
      differences between WCL9+ and WCL9- thymocytes. The WCL9- fraction could be
      stimulated much better with PHA than the WCL9+ fraction. Removal of adherent
      cells or adding adherent accessory cells did not influence this result.
      Immunochemical analysis showed that WCL9 reacted with a protein determinant
      present on two molecules (M(r): 200 and 155 kDa) under reduced and non-reduced
      conditions. These results, together with the absence of WCL9+ cells in other
      lymphoid organs, strongly suggest that WCL9 is a specific marker for early
      thymocytes.

PMID- 9241488
TI  - Mitogenic effect of naturally occurring elevated plasma prolactin on ring dove
      lymphocytes.
AB  - 3H-thymidine incorporation into isolated ring dove lymphocytes in vitro was used
      as a measure of lymphocyte proliferation. Lymphocytes taken from doves with
      increased plasma concentrations of prolactin demonstrated significantly increased
      3H-thymidine incorporation. In vitro incubation with mitogens significantly
      increased incorporation of 3H-thymidine into lymphocytes from non-breeding doves.
      However, similar treatment of lymphocytes taken from doves which had elevated
      levels of plasma prolactin failed to induce any further increase in the
      stimulation index. Antigen caused a significant increase in 3H-thymidine
      incorporation in non-breeding doves. Antigen administration also led to the
      production of specific antibodies. The titre of specific anti-human red blood
      cell (HRBC) agglutinins was greatest in those birds which also had elevated
      levels of plasma prolactin, reaching significance in the group of incubating
      doves with naturally occurring increased concentrations of plasma prolactin. The
      results presented here may be relevant to our understanding of the role of
      hormones such as prolactin on lymphocyte activation.

PMID- 9241489
TI  - Asthma mortality and antipsychotic or sedative use. What is the link?
AB  - Evidence in the medical literature suggests that patients with asthma who use
      antipsychotics or sedatives are at increased risk for serious complications of
      asthma. A number of mechanisms are potentially responsible for this observed
      association. The principle noncausal reasons for the increased risk of
      complications in this patient population include patient characteristics (such as
      the indication for antipsychotic use, noncompliance with asthma therapy, risk
      taking behaviour and family dysfunction) and treatment issues (including
      differential prescribing and the quality of medical care). The main causal
      mechanism involves depression of the CNS and impaired respiratory drive due to
      sedation during acute asthma attacks. Although it appears that most of the excess
      risk is a consequence of the noncausal mechanisms mentioned, physicians treating
      patients with asthma who have a history of antipsychotic use need to recognise
      the challenges inherent in managing such patients. Further research into the
      increased risk associated with sedative use is also warranted.

PMID- 9241490
TI  - Principles of signal detection in pharmacovigilance.
AB  - Adverse drug effects are manifold and heterogenous. Many situations may hamper
      the signalling (i.e. the detection of early warning signs) of adverse effects and
      new signals often differ from previous experiences. Signals have qualitative and
      quantitative aspects. Different categories of adverse effects need different
      methods for detection. Current pharmacovigilance is predominantly based on
      spontaneous reporting and is mainly helpful in detecting type B effects (those
      effects that are often allergic or idiosyncratic reactions, characteristically
      occurring in only a minority of patients and usually unrelated to dosage and that
      are serious, unexpected and unpredictable) and unusual type A effects (those
      effects that are related to the pharmacological effects of the drug and are
      dosage-related). Examples of other sources of signals are prescription event
      monitoring, large automated data resources on morbidity and drug use (including
      record linkage), case-control surveillance and follow-up studies. Type C effects
      (those effects related to an increased frequency of 'spontaneous' disease) are
      difficult to study, however, and continue to pose a pharmacoepidemiological
      challenge. Seven basic considerations can be identified that determine the
      evidence contained in a signal: quantitative strength of the association,
      consistency of the data, exposure response relationship, biological plausibility,
      experimental findings, possible analogies and the nature and quality of the data.
      A proposal is made for a standard signal management procedure at
      pharmacovigilance centres, including the following steps: signal delineation,
      literature search, preliminary inventory of data, collection of additional
      information, consultation with the World Health Organization Centre for
      International Drug Monitoring and the relevant drug companies, aggregated data
      assessment and a report in writing. A better understanding of the conditions and
      mechanisms involved in the detection of adverse drug effects may further improve
      strategies for pharmacovigilance.

PMID- 9241491
TI  - Switching between cyclosporin formulations. What are the risks?
AB  - The introduction of cyclosporin, refinement in surgical techniques and
      improvement in allograft preservation have all led to an improvement in graft and
      ultimately patient survival. Cyclosporin is a lipophilic cyclic polypeptide
      produced by Trichoderma, a fungus isolated from Norwegian soil. Cyclosporin is a
      potent, selective and powerful immunosuppressive agent possessing a narrow
      therapeutic window. Substitution among different formulations of cyclosporin for
      economic reasons, without close monitoring of pharmacokinetics and
      pharmacodynamics, can induce undesirable toxic effects. A number of recent
      reports, largely anecdotal, of adverse drug reactions and acute cellular
      rejection after conversion from the standard formulation to the microemulsion
      formulation of cyclosporin have created uncertainty over the therapeutic
      equivalency of these agents. This leading article reviews the pharmacology,
      pharmacokinetics and adverse drug reactions of cyclosporin as well as the
      potential risks associated with switching between cyclosporin formulations in
      stable renal transplant recipients. Caution should be employed when switching
      between cyclosporin formulations. Since data are limited, long-term prospective
      studies are necessary to delineate the role of high peak concentrations obtained
      from the microemulsion formulation in relation to cyclosporin-induced chronic
      nephropathy. The significance of the reduction in pharmacokinetic variability
      with use of the microemulsion formulation in terms of graft and patient survival
      remains unclear.

PMID- 9241492
TI  - Epidemiology and relative toxicity of antidepressant drugs in overdose.
AB  - Antidepressant drugs are currently the mainstay of treatment for all but the
      mildest forms of depression. Their effectiveness in the management of depressive
      illness is undisputed and their effectiveness in preventing suicide, while not
      proven, may be assumed. Nevertheless, of all the drugs that are taken in lethal
      overdose, prescribed antidepressants are among the most common. Epidemiological
      studies from several countries have provided evidence of marked differences in
      overdose toxicity between drug classes and, in some cases, between individual
      drugs within a class, with some of the older tricyclic antidepressants (TCAs)
      being the most toxic. Over 80% of all deaths arising from overdose of
      antidepressant medication in the UK between 1987 and 1992 were caused by 2 drugs:
      amitriptyline and dothiepin. Taken alone, this figure conveys little information
      about the toxicity of either drug. However, when considered within an
      epidemiological context, the evidence suggests that both drugs are highly toxic
      in overdose, a conclusion that is supported by animal studies of the toxicity of
      TCAs and by clinical evidence of overdose toxicity. This paper reviews the
      epidemiological evidence concerning the acute toxicity of antidepressant drugs
      and considers the interplay of factors that contribute to the toxicity which
      occurs when they are taken in acute overdose. The inherent toxicity of the drug
      appears to be the crucial factor and, although less well researched, prescribing
      practices and perception of toxicity are probable contributory factors.

PMID- 9241495
TI  - Access techniques in endoscopic fetal surgery.
AB  - Endoscopic surgery may in the future become an attractive alternative to open
      fetal surgery. Herein, we present our evolving experience with minimal access
      techniques in sheep and nonhuman primate models. Fifty-two pregnant sheep (term =
      145 d) were used. All underwent laparotomy. Cannulas were 5 mm diameter with
      balloon fixation device. In group I (95-105 d, n = 22, and 70-74 d, n = 19), a
      total of 119 cannulas were placed by open hysterotomy and pursestring suture
      through myometrium and membranes. In group II (n = 11), access was obtained by
      Seldinger guidewire technique. Eight cannulas were introduced over a dilator and
      7 were radially expanding endoscopic cannulas. Fifteen cannulas were also placed
      in 5 pregnant Rhesus monkeys using Seldinger and radially expanding techniques.
      Cannula removal was followed by insertion of a collagen sponge plug and
      oversewing of the myometrium. Mini-hysterotomies with purse-stringing provided
      excellent access to the amniotic cavity, without dissection of the membranes.
      Classic Seldinger technique with forward dilatation was equally effective, but
      caused stretching of membranes. In sheep and in primates, Seldinger technique
      with radial dilatation allowed safe access without membrane separation. Leak
      proof removal of the cannulas was achieved in all primates. Open hysterotomy with
      purse-string and balloon-tipped cannula provides efficient and safe access to the
      gravid sheep uterus. Seldinger technique allows equally secure access, and
      alleviates the need for hysterotomies. Radial dilatation of the porthole
      eliminates forward dissection of the membranes, both in sheep and primate models.
      This method, and collagen plug insertion upon completion of the endoscopic
      procedure, may provide a truly minimally invasive approach to in-utero surgery.

PMID- 9241493
TI  - Preliminary risk-benefit analysis of ropivacaine in labour and following surgery.
AB  - Ropivacaine is a new, long-acting local anaesthetic, prepared as a single
      enantiomer (the S form). Ropivacaine has a pKa of 8.07, a protein binding of
      approximately 94%, but a lower lipid solubility than bupivacaine. Extensive
      animal toxicological studies have shown a lower propensity for cardiotoxicity
      with ropivacaine than with bupivacaine. Studies in sheep have shown that the
      systemic toxicity of ropivacaine is not enhanced by gestation. Studies in human
      male volunteers have shown that ropivacaine is associated with at least 25% less
      CNS and cardiovascular adverse effects than bupivacaine following use of
      intravenous infusions of either drug at a rate of 10 mg/min, to a maximum dose of
      150 to 250 mg. With its lower toxicity, especially cardiovascular toxicity, and
      less intense motor blockade, ropivacaine may have advantages over bupivacaine in
      epidural pain relief during labour. In general, comparative studies have shown
      ropivacaine and bupivacaine to have similar efficacy, but ropivacaine has a
      greater degree of separation between motor and sensory blockade than bupivacaine
      when it given epidurally for epidural pain relief during labour (as intermittent
      doses or continuous infusion) or for caesarean section. A significantly lower
      rate of instrumental deliveries and significantly higher neurological and
      adaptive capacity scores in neonates at 24 hours were noted for following
      epidural relief during labour with ropivacaine in a meta-analysis of 6 studies
      comparing this agent with bupivacaine. Ropivacaine is also of great interest when
      used as an epidural infusion for postoperative analgesia. There are a few studies
      evaluating epidural infusions of ropivacaine 0.1%, 0.2% or 0.3% (10 ml/h for 21
      hours) after upper or lower abdominal or orthopaedic surgery, and epidural
      infusion of ropivacaine 0.2% (6 to 14 ml/h) after orthopaedic surgery. The
      studies show that ropivacaine provides postoperative pain relief in a dose
      related manner with minimal or a low degree of dose-related motor blockade.
      Recommended doses of ropivacaine given epidurally to control postsurgical pain or
      labour pain are 20 to 40 mg as a bolus with 20 to 30 mg as a top-up with an
      interval > or = 30 minutes. Alternatively, ropivacaine 2 mg/ml (0.2%) can be
      given as a continuous epidural infusion at a rate of 6 to 14 ml/h (lumbar) or 4
      to 8 ml/h (thoracic). Epidural ropivacaine 0.2% provides a good level of
      analgesia with minimal motor block, but the effects of a combination of
      ropivacaine and an opioid administered epidurally could have potential and need
      to be investigated. Preoperative or postoperative subcutaneous wound
      infiltration, during cholecystectomy or hernia repair, with ropivacaine 100 to
      175 mg has been shown to be more effective than placebo and as effective as
      bupivacaine in reducing wound pain. The adverse effects associated with epidural
      administration of ropivacaine include hypotension, nausea, bradycardia, transient
      paraesthesia, back pain, urinary retention and fever. In comparative studies of
      ropivacaine and bupivacaine, the 2 drugs appear to be associated with a similar
      incidence of similar types of adverse effects excluding cardiovascular and CNS
      toxicities which are lower with ropivacaine. In conclusion, ropivacaine is
      effective for pain relief during labour and in the postoperative period.
      Ropivacaine is associated with less cardiovascular and CNS toxicity than
      bupivacaine and provides a greater degree of dissociation between sensory and
      motor effects producing less intense motor blockade and more rapid recovery to
      full patient mobilisation.

PMID- 9241497
TI  - Motility studies of the esophagus in a case of esophageal atresia before primary
      anastomosis and in experimental models.
AB  - Esophageal motility was assessed in a case of long-gap esophageal atresia (EA)
      without tracheoesophageal fistula before primary anastomosis, in addition
      esophageal manometrical studies were also experimentally performed in mongrel
      dogs to investigate the pathogenesis of the motility disorders in successfully
      repaired EA. Coordinated peristaltic contractions were observed between the
      proximal and distal esophageal pouch when swallowing before primary anastomosis
      in EA. In addition, these contractions induced a reflex relaxation of the lower
      esophageal sphincter (LES) as seen in the normal esophagus at the age of 8
      months. At the age of 28 days, however, the LES showed an unstable pressure
      profile and the absence of a reflex relaxation in response to the contractions of
      the proximal esophageal pouch. On the other hand, experimental studies were
      carried out on six mongrel dogs weighing 12-15 kg. In group 1 (n = 3), the
      esophagus was divided at the level of the tracheal carina and both the proximal
      and distal pouches were closed separately. In group II (n = 3), the esophageal
      branches of the vagal nerves were divided between the level of the aortic arch
      and the esophageal diaphragmatic hiatus. Postoperatively, coordinated peristaltic
      contractions were shown between the proximal and distal esophageal pouches in
      group I, although the vagotomized esophagus showed abnormal simultaneous
      contractions in group II. These results suggested that even if the esophageal
      continuity is disrupted, the coordinated peristaltic contractions are propagated
      between the proximal and distal esophagus before primary anastomosis in EA, and
      thus postoperative esophageal motility disorders may result from the surgical
      damage to the vagus during operative procedures.

PMID- 9241496
TI  - Postpneumonic empyema in children treated by early decortication.
AB  - We performed early decortication in 32 cases of postpneumonic empyema during the
      period of February 1991 to December 1995. Twenty of them were male and 12 of them
      were female. We evaluated these cases retrospectively. Decortication was saved
      for the patients where antimicrobial therapy and closed-tube drainage had failed
      to achieve a cure and was performed on the 10-15th day after the diagnosis was
      established. Indications for the decortication were persistent fever (9),
      pulmonary air leakage (7), localized effusion (7), persistent respiratory
      distress (5) and pleural thickening without resolution (28). Decortication was
      performed through the standard posterolateral thoracotomy. Patients were
      discharged on the 8th postoperative day with minimal morbidity and no mortality.
      Because of the simplicity of the procedure (short hospitalization periods, low
      mortality and morbidity rates) good results were achieved with early
      decortication.

PMID- 9241494
TI  - Antipsychotic use in pregnancy. What are the best treatment options?
AB  - Both the rapid emergence of new antipsychotic medications and the increasing
      fertility rate among women with psychotic disorders have contributed to the
      growing clinical importance of the treatment of pregnant women who have psychotic
      illnesses. The treatment of this patient population must always take into
      consideration the effect of that treatment on the fetus. With regard to the high
      risk of decompensation during pregnancy and postpartum, continuous antipsychotic
      medication is needed using the minimum effective dose. The use of high-potency
      agents appears to be preferable for first-line management, as there are few data
      regarding the use of atypical agents such as clozapine in pregnancy. Guidelines
      for treating pregnant women with psychoses vary little from those for nonpregnant
      patients. Clinicians must always carefully weigh up the risks and benefits for
      each patient on an individual basis.

PMID- 9241498
TI  - Gastric transposition for esophageal replacement in children--an Indian
      experience.
AB  - Most pediatric surgeons are wary of gastric transposition as a means for
      esophageal replacement in children, especially during infancy. We present our
      initial experience of this technique in five children followed up for an average
      1.7 years postoperatively. Four of them were infants (age range 5 m to 10 m at
      the time of transposition) with wide-gap esophageal atresia, while one was
      operated upon for an extensive corrosive esophageal stricture at 4 years age. The
      stomach was placed transhiatally in 3 patients and through the retrosternal route
      in 2 patients. A gastric outlet drainage procedure was performed in all cases.
      The average age at transposition in the 4 infants with esophageal atresia was 8.5
      months and the mean weight was 7.4 kg. Three of the four infants required
      postoperative ventilation (mean duration 40 hours) and the average duration of
      hospital stay was 24 days. Our first transposition in a chubby infant resulted in
      death (20% mortality for this series) due to difficult ventilation. Other
      complications included anastomotic leak and subsequent stricture (one patient),
      adhesive obstruction (one patient), transient Horner's syndrome and recurrent
      laryngeal nerve palsy (one patient), and poor weight gain (one patient).
      Postoperatively, while the pattern of liquid gastric emptying was variable, no
      duodenogastric reflux was demonstrable. Thus gastric transposition is a safe,
      relatively simple and physiologic procedure in infancy and childhood and has
      given good functional results.

PMID- 9241499
TI  - Recurrent intestinal bleeding from jejunojejunostomy caused by portal
      hypertension following hepatoportojejunostomy in extra hepatic biliary atresia
      (EHBA)--successful treatment by transjugular intrahepatic portosystemic shunt
      (TIPS).

PMID- 9241500
TI  - Urolithiasis in patients with Hirschsprung's disease.
AB  - Although patients with Hirschsprung's disease (HD) carry some factors that
      increase the risk of urolithiasis this fact seems to be underestimated. Among 302
      patients with HD, four patients (1.32%) with urolithiasis were encountered. Since
      factors increasing the risk of urolithiasis such as urinary tract infection,
      constipation, vesicoureteral reflux, enteric resections and malabsorption may be
      encountered during the course of HD, an increased risk of urolithiasis in these
      patients should be expected.

PMID- 9241501
TI  - Markedly improved survival in malignant sacro-coccygeal teratomas--16 years,
      experience.
AB  - AIM OF STUDY: To see the impact of cisplatin- and carboplatin-based protocols on
      survival in malignant sacrococcygeal teratomas (SCT). METHODS: Twenty infants and
      children with malignant SCT were treated at the Hospital for Sick Children, Great
      Ormond Street, London, over a 16-year period from 1979 to 1994. There were 5
      males and 15 females, age ranged from 1 day to 3.5 years (mean 18 months).
      RESULTS: Twelve patients (60%) had distant metastasis: 9 lung metastasis, 2 liver
      involvement, 2 bony metastases, 1 cerebral metastasis and 1 bilateral inguinal
      lymph node deposits. From 1982 to 1986, patients received the BEP chemotherapy
      protocol which included cis-platinum, bleomycin and etoposide (VP 16). After
      1986, cis-platinum was replaced with carboplatin in the new JEB protocol. Patient
      1 did not receive any chemotherapy, Patients 2-4 received varying protocols (2
      deaths), Patients 5-8 received the BEP regime (1 death) and Patients 9-20
      received JEB (1 death). The first three deaths were due to uncontrolled local
      disease and/or metastasis, while the latter death was due to bleomycin toxicity.
      Overall, 9 of 12 (75%) patients with distant metastasis survived as opposed to 7
      of 8 (88%) patients with localised disease. Of the 12 patients who received the
      JEB protocol, 11 (92%) survived, including 7 patients with metastatic disease and
      2 with local recurrence. Seven patients (35%) had relapse while on treatment or
      follow-up, 4 of these are disease-free with further therapy. In 6 of these
      children, serum AFP rose before there was clinical or radiological evidence of
      relapse. In 2 other patients, further chemotherapy was recommenced solely on the
      basis of rising serum AFP, these patients did not subsequently develop overt
      metastasis. CONCLUSIONS: We conclude that the treatment of choice for malignant
      SCT is the JEB regime, to be given for 4 courses or to be continued for 2 courses
      beyond documented Complete Response (CR). Excision of the primary tumour and
      coccyx should be done in all cases even if a CR has been documented. Metastases
      not responding to chemotherapy would need appropriate surgery, radiotherapy is
      hardly ever needed. An overall cure rate exceeding 90% can be expected.

PMID- 9241502
TI  - The effect of suturing technique and material on complication rate following
      hypospadias repair.
AB  - Ninety-seven children with distal hypospadias were treated surgically using
      perimeatal-based flap urethroplasty (Mathieu procedure) in a two and a half years
      period. A review of the medical records revealed two distinct groups of patients
      according to the suturing type and suture material. In the first group of 36
      patients (group I), neourethra was constructed using 6/0 polyglactine (Vicryl) in
      a single layer, full-thickness, uninterrupted fashion. Skin flaps were
      approximated using interrupted simple 5/0 polyglactine (Vicryl) sutures. In the
      second group of 61 patients (group II), 7/0 polydioxanone (PDS) was used in the
      urethral anastomosis performed in a subcuticular, uninterrupted fashion. The skin
      flaps were closed using interrupted simple 5/0 rapidly absorbable polyglactine
      (Rapid Vicryl) sutures. Patients were followed-up from 6 to 12 months. Urethral
      or meatal stenosis was not observed in any patient. There was no infectious
      complication. Urethrocutaneous fistula rate was significantly higher in group I
      (16.6%) compared to group II (4.9%) (p < 0.01). Complication rate following
      hypospadias repair can be reduced by the use of a subcutaneous suture technique
      utilizing polydioxanone suture material in urethroplasties.

PMID- 9241503
TI  - A new treatment with bleomycin for complicated cutaneous hemangioma in children.
AB  - Cutaneous hemangiomas are the most common tumors of infants and children.
      Although they frequently resolve spontaneously, approximately 5% produce
      complications such as bleeding, infection, consumption coagulopathy and
      unesthetic appearance. Various methods of treatment are described for these
      complicated hemangiomas. We used a new type of treatment for complicated
      cutaneous hemangiomas as intralesional bleomycin (BLM) injection, for the first
      time in the literature. This agent produced extensive fibrosis and spontaneous
      resolution of hemangiomas. Fourteen patients with complicated hemangiomas (twelve
      capillary and two cavernous) have been treated with this method during a three
      years period. Of these fourteen patients, five had bleeding, three had infection,
      one had ulceration, and five had unesthetic appearance and continued rapid
      growth. Lesions of three patients were completely excised after only one BLM
      injection. In the other eleven patients lesions regressed 60-100% during 6-14
      months with two to three BLM injections. We believe that intralesional BLM
      injection is simple, and very useful for treatment of complicated cutaneous
      hemangiomas.

PMID- 9241504
TI  - The fate of undescended testes in patients with gastroschisis.
AB  - Cryptorchidism is frequently associated with gastroschisis, yet little is
      published on its management in such circumstances. In a review of 10 consecutive
      boys with gastroschisis since 1980, 4 had undescended testes. Gestational age and
      birth weight did not differ from the 6 boys with normally descended testes. The
      first two patients had associated arthrogryposis multiplex congenita. The first
      underwent bilateral orchidopexy at 9 years of age for inguinal testes. In the
      second patient, the left testis was intraabdominal at the level of the sigmoid
      colon at birth; at 3 months of age, when a left inguinal hernia repair was
      required, left groin exploration revealed the testis at the internal ring and
      orchidopexy was performed successfully. In the third patient the left spermatic
      vessels were divided at the time of gastroschisis repair and the testis anchored
      in the prebubic area. The second-stage orchidopexy was performed at 16 months. In
      the last patient the intraabdominal testis could be placed in a scrotal pouch
      without mobilisation or division of the vessels. From our experience and a review
      of the literature we conclude that: 1) undescended testes are frequently
      associated with gastroschisis; 2) mechanical factors rather than prematurity are
      likely responsible for this association; 3) if the testis easily reaches the
      scrotum, orchidopexy can be done safely at the time of gastroschisis repair; 4)
      if the testis does not reach easily and appears to have a gubernaculum, it may be
      preferable to leave it in place since spontaneous descent can occur.

PMID- 9241505
TI  - An unusual presentation of a tracheo-oesophageal fistula.

PMID- 9241506
TI  - Closed perforation of the esophagocardiac junction with Bochdalek hernia.

PMID- 9241507
TI  - Atypical hemihepatectomy during primary CDH-repair in a neonate on ECMO.
AB  - We report the case of a newborn with a large left-sided congenital diaphragmatic
      hernia (CDH) who required extra corporeal membrane oxygenation (ECMO) for severe
      respiratory insufficiency. CDH repair had to be performed on bypass circulation.
      Intraoperatively, an atypical hemihepatectomy of the herniated lobe was
      conducted, because reposition of the liver led to a kinking of the vena cava and
      to a torsion of the right lobe, resulting in ischemia and compromised venous
      flow. The extraordinary anatomical indication and the potential danger of
      uncontrollable bleeding are discussed.

PMID- 9241508
TI  - Hirschsprung's disease presenting as sigmoid volvulus in a newborn.
AB  - This report describes a 1-day-old term boy with sigmoid volvulus secondary to
      Hirschsprung's disease. The presentation and treatment are outlined.

PMID- 9241509
TI  - Repair of congenital H-type vestibuloanorectal fistula through the posterior
      midsagittal approach: case report.
AB  - The posterior midsagittal approach was successfully used for the repair of
      congenital H-type vestibuloanorectal fistula in a patient 1.5 months old.
      Technical details of the operation which consisted of two main parts are
      described. Identification and dissection of the fistulous tract started following
      midsagittal division of the sphincters and the posterior half of the rectum with
      the patient in a knee-chest position. The dissected part of the fistulous tract
      was inverted per vagina. Completion of dissection and excision of the fistulous
      tract were accomplished with the patient in the lithotomy position. The main
      advantage of the procedure was the ability to completely excise the fistula under
      direct vision.

PMID- 9241510
TI  - Salvage treatment of relapsing Wilms' tumour by autologous bone marrow
      transplantation.
AB  - Despite the remarkable success in treatment of Wilms' tumour there is still a
      small group who will suffer from relapse. The optimal therapy for relapsing Wilms
      tumour has not been determined. We have treated four children with high-dose
      chemotherapy (HDC) followed by stem-cell support known as autologous bone marrow
      transplantation (ABMT). The patients were two girls and two boys aged 1-9 years.
      The histology was favourable in 3 cases and unfavourable, clear cell sarcoma, in
      1. The relapses were pulmonary in 2 cases and skeletal in 2 cases. There was no
      detectable disease prior to ABMT. After ABMT 2 children got further relapses and
      died. On the other hand 2 children had no further relapse and are alive and well
      1.5-2.5 years later. Treatment with HDC and ABMT is complicated and expensive but
      may be of benefit and should be added to the treatment options in children with
      otherwise poor prognosis of Wilms' tumour.

PMID- 9241511
TI  - Mesenteric adenitis caused by Yersinia pseudotuberculosis presenting as an
      abdominal mass.
AB  - Infection by Yersinia pseudotuberculosis has become of increasing pathological
      importance. Patients normally present with symptoms similar to those of
      appendicitis, due to mesenteric adenitis. We present the case of 3 patients
      infected by Yersinia pseudotuberculosis who in addition to fever and abdominal
      pain had a palpable abdominal mass, so great was the enlargement of the
      mesenteric nodes. In 2 patients a laparotomy was carried out, followed by biopsy
      of a mesenteric lymph node. The diagnosis of Yersinia infection was confirmed by
      bacterial culture of the biopsied material and also by serology. In the third
      patient, serological studies and ultrasonic imaging of the abdomen led to early
      diagnosis and surgery was avoided. We suggest that a diagnosis of mesenteric
      adenitis due to Yersinia pseudotuberculosis should now be considered in all
      patients presenting with an abdominal mass, and in whom there is an appropriate
      clinical and epidemiological history. The diagnosis should be confirmed by
      abdominal ultrasound (alternatively Computerised Axial Tomography or Magnetic
      Resonance Imaging) and serological studies. In this way, unnecessary surgery can
      be avoided.

PMID- 9241512
TI  - Congenital hypertrophic pyloric stenosis with associated polyhydramnios in a
      premature infant.
AB  - Congenital pyloric stenosis is rare in premature infants. This is a report of
      pyloric stenosis in a premature infant (35 weeks gestation) discovered on the 2nd
      day of life. There appears to be an association with polyhydramnios. Congenital
      hypertrophic pyloric stenosis should be considered in the differential diagnosis
      of premature infants with upper gastrointestinal symptoms. A review of the
      literature is included.

PMID- 9241513
TI  - Ilio-psoas abscess in the neonate.
AB  - Ilio-psoas abscess is rare in children and exceptional in the neonate. This
      report describes a case of idiopathic ilio-psoas abscess in a neonate with no
      etiologic factor known. The diagnosis was made by ultrasonography and computed
      axial tomography. The treatment was extraperitoneal surgical drainage and
      systemic antibiotics.

PMID- 9241514
TI  - Dynamics of complex systems.

PMID- 9241515
TI  - Modeling and decomposition of HRV signals with wavelet transforms.

PMID- 9241516
TI  - Compression of ECG data by vector quantization.

PMID- 9241517
TI  - Extraction of 40 Hz EEG bursts for chaos analysis of brain function.

PMID- 9241518
TI  - Detecting myocardial ischemia with 2-D spectrum analysis of VCG signals.

PMID- 9241520
TI  - 3-D imaging and stereotactic radiosurgery.

PMID- 9241519
TI  - A new approach to medical image reconstruction.

PMID- 9241521
TI  - Molecular electronics: strategies and progress in China.

PMID- 9241522
TI  - Feature extraction in image analysis. A program for facilitating data reduction
      in medical image classification.

PMID- 9241523
TI  - Acoustic analysis of pathological voices. A voice analysis system for the
      screening of laryngeal diseases.

PMID- 9241524
TI  - Using nonlinear dynamic metric tools for characterizing brain structures.

PMID- 9241526
TI  - Thinking twice about "tissue engineering".

PMID- 9241525
TI  - The modulation transfer function. A simplified procedure for computer-aided
      quality evaluation in mammography.

PMID- 9241527
TI  - Analyses of extrathymic T cell differentiation in nu/nu mice by grafting
      embryonal organs.
AB  - Fetal (days 15 to 17) organs such as the small intestine, stomach and pancreas
      were engrafted under the renal capsules of athymic nude (nu/nu) mice to examine
      the capacity of these organs to induce the differentiation of T cells. Eight
      weeks after engraftment, the engrafted organs had differentiated into adult-type
      organs histologically. In the lamina propria of the engrafted small intestine,
      large intestine, and stomach, there were clusters of lymphocytes or lymphoid
      follicles, which included Thy1.2+ or CD4+ T cells. Flow cytometric analyses
      revealed that the lymphocytes from the lymph nodes of sham-, esophagus-, or
      pancreas-engrafted mice included very few T cells (1.20%), whereas those from the
      lymph nodes of the fetal small intestine-, large intestine-, or stomach-engrafted
      mice included significant numbers of T cells (8.36%) 8 weeks after engraftment,
      although there were not as many as in the fetal thymus-engrafted mice (17.97%).
      The peripheral T cells in the small intestine-, large intestine-, or stomach
      engrafted mice were of bone marrow origin, and consisted of Thy1.2+, CD3+, and
      CD4+8-, or CD4-8+ with T cell receptor (TcR) alpha beta cells. Taken together,
      these findings indicate that not only the murine small intestine and large
      intestine but also the stomach have the capacity to induce the differentiation of
      T cells.

PMID- 9241528
TI  - CD8+ tumor-specific Tc cells primed in vivo or in vitro against the BALB/c
      plasmacytoma ADJ-PC-5 use the same TcR V beta families but display distinct TC1
      or TC2 characteristics.
AB  - The involvement of counteractive CD8+ T cell subsets in tumor-specific
      unresponsiveness was analyzed in a syngeneic murine tumor model. CD8+ cytotoxic T
      cells against the IL-10 producing BALB/c plasmacytoma ADJ-PC-5 can be easily
      induced in vitro, in a primary syngeneic mixed lymphocyte tumor cell culture
      (MLTC), or in vivo, by repeated immunization of syngeneic BALB/c mice with high
      doses of X-irradiated ADJ-PC-5 tumor cells. Long term cultivated CD8+ ADJ-PC-5
      specific Tc lines use either TcR of the V beta 6 or V beta 8.1/8.2 type,
      irrespective if the lines were derived from a primary MLTC or from immunized
      mice. While most of the Tc lines produce type-1 cytokines (IFN-gamma, no IL-4)
      upon stimulation, at least two of them, which were derived from a primary MLTC,
      display a type-2 cytokine spectrum (IL-4, no IFN-gamma). The primary in vitro Tc
      response against ADJ-PC-5 cells shows characteristics of a TC2 response: CD8+ Tc
      cells which are induced in a primary MLTC do not produce IFN-gamma, and the tumor
      specific Tc response is enhanced by IL-4 but suppressed by IFN-gamma or IL-12. In
      contrast, ADJ-PC-5-specific CD8+ Tc cells from immunized mice are IFN-gamma
      producing TC1 cells. Since the primary in vitro Tc response against the tumor is
      suppressed even by lowest numbers of irradiated ADJ-PC-5-specific TC1 cells via
      IFN-gamma, these TC1 cells behave similar to a previously described regulatory
      subset of IFN-gamma producing CD8+ T cells, which are induced during early stages
      of ADJ-PC-5 tumorigenesis and inhibit the induction of a tumor-specific Tc
      response from naive BALB/c spleen cells in vitro.

PMID- 9241529
TI  - The appearance of unusual phenotypic cells (CD4+ Mac-1+ class II+) in the liver
      of (NZW x BXSB)F1 mice is possibly an animal model for autoimmune hepatitis.
AB  - The male (NZW x BXSB)F1 (W/BF1) mouse, a murine model for autoimmune diseases,
      shows hepatosplenomegaly with lymphoid cell infiltration in the liver by 20 weeks
      of age. The majority of infiltrating cells are T cells, B cells and plasma cells,
      as seen in autoimmune hepatitis. Together with the increase in serum glutamate
      pyruvate transaminase (GPT) levels, anti-dsDNA antibody (Ab) and circulating
      immune complex (CIC) levels increase with age. These findings are compatible with
      those of autoimmune hepatitis in humans. In addition, a unique finding in this
      mouse is the accumulation of CD4+ Mac-1+ Class II+ cells in the sinusoidal space.
      The cells have the capacity to proliferate and differentiate into macrophages in
      vitro, indicating that they are the precursors of macrophages. This W/BF1 mouse
      provides a useful tool for not only analyzing the pathogenesis of autoimmune
      hepatitis but also establishing a new therapeutic strategy for it. In addition,
      we discuss the significance of the appearance of abnormal cells in autoimmune
      prone mice.

PMID- 9241530
TI  - In staphylococcus enterotoxin B (SEB)-stimulated human PBMC, the LAK activity of
      non-T cells might have a major role in the mechanism of glomerular endothelial
      cells' injury.
AB  - In this study the SEB-activated LAK cytotoxicity was identified and characterized
      in human peripheral blood lymphocytes (PBMC). After 3 days of SEB stimulation,
      the PBMC acquired a cytotoxicity against traditional LAK targets, K-562 and
      Daudi, beside that human glomerular endothelial cells (HGEC) were effectively
      lysed. The magnetic separation of SEB-stimulated CD5+ T cells revealed that the
      dominant LAK cytotoxicity remained in the CD5- lymphocyte fraction. The major
      part of the SEB-generated cytotoxicity of CD5- cells could be blocked with
      specific antibodies to IL-2 and IFN-gamma. The IFN-gamma pretreatment of HGEC
      reduced the target sensitivity, but because of the upregulation of MHC class II
      on HGEC surface, these cells were able to present SEB to CD5+ cells. These
      results suggested that in bacterial superantigen-mediated infection, the non-T
      (NK cells-derived) LAK cells might have a primary pathogenic role, and the
      adverse effect of IFN-gamma, that was massively secreted from superantigen
      stimulated cells, requires greater consideration.

PMID- 9241531
TI  - Rapid mitogen-induced aminopeptidase N surface expression in human T cells is
      dominated by mechanisms independent of de novo protein biosynthesis.
AB  - The membrane bound metalloprotease aminopeptidase N (APN, CD13, EC 3.4.11.2) is a
      well established marker of normal and malignant cells of the myelo-monocytic
      lineage. It is also expressed by leukaemic blasts of a small group of patients
      suffering from acute or chronic lymphoid leukaemia. Recently, the expression of
      the APN gene in T cell lines as well as the induction of APN gene and surface
      expression in human peripheral T cells by mitogenic activation have been
      demonstrated. Here, by means of cytofluorimetric analysis evidence is provided,
      that the induction of APN surface expression is partially resistent to the action
      of the inhibitors of protein biosynthesis, puromycin and cycloheximide, and is
      not prevented by tunicamycin, an inhibitor of glycosylation. These data suggest
      that the rapid mitogen-induced surface expression of APN, detectable 20 hours
      after stimulation is dominated by mechanisms not dependent on de novo protein
      biosynthesis or glycosylation. As shown by simultaneous analyses, the inhibitors
      used did also differently modify the induction of surface expression of other
      inducible glycosylated leukocyte surface antigens, namely CD25, CD69 and CD95.

PMID- 9241532
TI  - Anti-CD53 monoclonal antibody induced LFA-1/ICAM-1-dependent and -independent
      lymphocyte homotypic cell aggregation.
AB  - CD53 is a pan-leukocyte glycoprotein and belongs to a member of the tetraspan
      family of cell membrane proteins. The predicted structure and functional
      characteristics of CD53 suggest that it may play important roles in transmembrane
      signaling, but its roles in cell adhesion have not been clarified. The present
      study shows that anti-CD53 monoclonal antibody (mAb), HI29 induced homotypic cell
      aggregation of lymphoid cell lines including a B cell line from a patient with
      leukocyte adhesion deficiency syndrome (LAD). The homotypic cell aggregation was
      blocked by another anti-CD53 mAb, MEM53, in all the examined cell lines and by
      anti-LFA-1 (CD11a/CD18) or anti-ICAM-1 (CD54) mAbs in the cell lines except for
      the LAD line, but it was not blocked by anti-CD44 or anti-CD49d mAb. The induced
      homotypic cell aggregation was energy-dependent. These findings suggest that CD53
      relates to LFA-1/ICAM-1-dependent and -independent pathways of homotypic cell
      aggregation of lymphocytes and that it plays an important role in lymphocyte
      activation and cell adhesion.

PMID- 9241533
TI  - Leukosialin (CD43) is proteolytically cleaved from stimulated HMC-1 cells.
AB  - Leukosialin (CD43), the major sialoprotein on circulating leukocytes, has been
      previously described to be down-regulated on neutrophils following activation
      with phorbol myristate acetate (PMA). The other single cells previously examined,
      blood lymphocytes, do not down-regulate CD43 when stimulated by PMA. Recently, we
      have characterized leukosialin on the human mast cell line HMC-1 and observed
      that leukosialin is down-regulated after stimulation with PMA. In the present
      study, we have investigated the mechanism of PMA-mediated down-regulation of CD43
      on HMC-1 cells (subclone 5C6). PMA caused the release of soluble leukosialin (123
      kD) during HMC-1 cell activation. The molecular weight of soluble leukosialin was
      nearly identical to that of the cell-membrane bound molecule, suggesting a
      cleavage proximal from the cell membrane. Inhibitors of serine proteases, like
      phenylmethylsulphonyl fluoride (PMSF), benzamidine and 3, 4-dichloroisocoumarin,
      blocked the PMA-mediated cleavage of CD43. In all experiments, the inhibition of
      CD43-down-regulation was dependent on the concentration of protease inhibitors.
      Treatment of HMC-1 cells with various proteases (trypsin, alpha-chymotrypsin,
      elastase, papain, nagarse) substantially decreased anti-CD43 binding capacity and
      caused the release of soluble leukosialin (116 kD) or its fragments into the
      supernatant. Pretreatment of HMC-1 cells with neuraminidases from Vibrio cholerae
      or Arthrobacter ureafaciens resulted in an increased sensitivity of CD43 against
      proteases, whereas the effects of PMA were not influenced. In conclusion,
      proteolytic cleavage of CD43 is described for the first time in a cell other than
      neutrophils, namely HMC-1 cells. Our results suggest that serine proteases are
      involved in the PMA-mediated down-regulation of leukosialin on HMC-1 cells.

PMID- 9241534
TI  - Galectin-3 inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF)
      driven rat bone marrow cell proliferation and GM-CSF-induced gene transcription.
AB  - The expression of galectin-3 (formerly known as IgE-binding protein or Mac-2) in
      rat bone marrow (BM) was investigated by FACS, immunocytochemical and immunoblot
      analysis. The functional significance of rat recombinant galectin-3 on mouse
      recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven
      proliferation of macrophage progenitors and gene transcription was further
      examined. Immunocytochemical analysis of in situ BM sections demonstrated
      galectin-3 in myelopoietic cells and surrounding stroma, whereas erythropoietic
      and lymphopoietic environments essentially lacked galectin-3 expression. FACS
      analysis demonstrated that incubation of freshly isolated BMC with lactose, a
      competing ligand for galectin-3 binding to glycoconjugates, decreased binding of
      antigalectin antibodies to cells primarily expressing the myeloid antigen
      recognized by mAb His-54. Similarly, lectin-mediated binding of exogenous
      galectin-3 to myeloid lineage cells was also demonstrated. Immunoblot analysis of
      BM eluates demonstrated galectin-3 both in the extracellular matrix and in a
      lactose elutable form, bound to the surface of BMC. [3H]Thymidine incorporation
      studies on BMC cultured in the presence of galectin-3 demonstrated suppression of
      GM-CSF-induced proliferation by galectin-3. In addition, differential display
      analysis of immediate early gene expression in BMC cultured in the presence of
      galectin-3 revealed a 76.2% inhibition of GM-CSF-induced gene transcription by
      galectin-3 assessed by the number of PCR-fragments generated. Our data suggest a
      role for galectin-3 in the organization of myelopoietic compartments in rat BM
      and regulation of the action of growth factors on myelopoietic precursor cells.

PMID- 9241535
TI  - Phenotypic changes of monocytes induced by HIV-1 gp120 molecule and its
      fragments.
AB  - Several phenotypic and functional changes of monocytes (M phi) have been
      described in HIV-1+ subjects and AIDS patients. Some of these changes that are
      pertinent for immunopathogenesis of the disease may be induced by HIV-1 envelope
      glycoprotein 120 (gp120). In the present study the effect of recombinant full
      length gp120 (FLgp120) and its two fragments: rp120cd (aa 410-511) and rp120 (aa
      446-511) on the expression of the surface molecules of M phi cultured in vitro
      was determined. The FLgp120 and rp120cd caused upregulation of CD14 and CD44. The
      rp120cd peptide significantly increased the expression of CD16 (Fc gamma receptor
      type III) and TNF receptor type II. In contrast, the rp120 downregulated HLA-DR,
      CD64 (Fc gamma RI), interferon gamma receptor and induced IL-10 production by M
      phi. This study indicates that gp120 molecule and its fragments may induce
      several phenotypic changes of M phi in particular the increased proportion of
      CD14+CD16+ cells that is observed in the blood of AIDS patients. These results
      provide further evidence for variable response of M phi to gp120 which may
      explain the variability of phenotypic changes and heterogeneity of M phi subsets
      seen in HIV-1 disease.

PMID- 9241536
TI  - Role of naive and memory T cells in tumor cell lysis mediated by bi-specific
      antibodies.
AB  - Bispecific monoclonal antibodies (Bi-mAb) with specificity for a tumor associated
      antigen and the CD3 or CD28 antigen on T lymphocytes, respectively, induce
      activation of resting T lymphocytes and target-specific tumor cell lysis. Former
      studies had confirmed that T cells expressing the CD45RO "memory" antigen at high
      levels were the most potent effectors of Bi-mAb-mediated cytotoxicity when
      compared to their "naive" counterparts expressing the CD45RA antigen. Further
      analysis of the T cell subpopulations revealed that within the memory T cell
      pool, CD8+ T cells were the effector cell, population with strongest cytolytic
      activity. The cytolytic activity was correlated with the expression level of
      perforin and granzymes B mRNA. Ca2+ complexing agents, which abrogate perforin
      activity, reduced necrosis, while inhibition of granzyme activity in effector or
      target-cells had a similar effect on apoptosis. These results confirm the crucial
      role perforin and granzymes play in target-cell lysis and explain why CD8+CD45RO+
      T cells activated by combined CD3 and CD28 antigen triggering represent the T
      cell pool with highest cytolytic potential.

PMID- 9241537
TI  - Giant intra-adrenal myelolipoma associated with recurrent urinary tract
      infection.
AB  - Adrenal myelolipomas are rare benign tumours that may be identified on routine
      imaging studies. The association of myelolipomas with obesity, hypertension and
      malignant tumours has been reported. We describe a giant intra-adrenal
      myelolipoma in a 40-year-old woman that is the largest asymptomatic tumour of
      this type documented in the past 10 years. To avoid unnecessary and extensive
      treatment, the distinction of benign from malignant adrenal tumours or extra
      medullary haematopoietic tumour is important, particularly when a small, inactive
      adrenal mass is found incidentally.

PMID- 9241538
TI  - Enzymuria as early marker of interstitial nephritis.

PMID- 9241539
TI  - Intravenous aminophylline increases the degree of saturation of urine with
      calcium phosphate and struvite.
AB  - This study was designed to assess the effect of i.v. treatment with aminophylline
      (AMPH) on the risk of calcium phosphate and struvite stone formation. We
      administered AMPH in doses of 4 mg/kg body weight in 15-min i.v. infusions to 60
      infants with clinical symptoms of obstructive bronchitis with dyspnoea. During 3
      hours after infusion we observed a significant increase in urine saturation with
      brushite, octocalcium phosphate and struvite. This rise in urine saturation may
      increase the risk of kidney stone formation.

PMID- 9241540
TI  - Experience in 3,500 patients with urinary stones treated with the Dornier HM-4
      bath-free lithotriptor.
AB  - During a 3-year period, hundreds of patients underwent ESWL treatment with the
      Dornier HM-3 and HM-4 lithotriptors operating at our institution. Our experience
      in 3,500 patients treated with the HM-4 bath-free lithotriptor is reported.
      Patients with radiolucent or cystine stones, stones larger than 3 cm or staghorn
      calculi, multiple stones with a total burden of more than 3 cm and those not
      amenable to follow-up were excluded from the study. The overall stone-free rate
      was 70.7% and 81% at 1 and 3 months, respectively. The stone-free rates at 1 and
      3 months were further determined by the exact location of each stone within the
      urinary tract. Stone-free rates at 3 months ranged from 90.84% for renal pelvic
      stones to 71.08% for lower calyceal stones, while the stone-free rates for
      ureteral calculi ranged from 80.85% for upper third unstented ureteral stones to
      92.92% for lower ureteral stones. The overall complication rate was 6.02% with a
      1.2% post-ESWL intervention rate (ureteroscopy or placement of percutaneous
      nephrostomy or stent).

PMID- 9241541
TI  - Maternal urological injuries associated with vaginal deliveries: change of
      pattern.
AB  - Injury to the maternal lower urinary tract is related to the standard of
      obstetric care and to different techniques utilized in delivery. In comparison
      with operative delivery, maternal urinary tract injury in association with
      vaginal delivery had always been exceptionally rare. However, with the recent
      progress in obstetric care and the introduction of new concepts such as vaginal
      delivery after caesarian section (VDAC), the pattern of maternal urological
      injuries associated with vaginal deliveries might have changed. In a
      retrospective study it was found that significant injuries to the lower urinary
      tract occurred in seven females in the course of vaginal delivery in the period
      between 1992 and 1994 in two major hospitals in the Riyadh area. These included
      rupture of the posterior bladder wall, trigone and bladder neck. Distal ureteric
      and urethral injuries, as well as bladder contusion were also encountered. Two
      patients developed vesico-uterine and vesico-vaginal fistulas. History of
      previous caesarian section was present in 4 patients. All deliveries were with
      cephalic presentation and six patients received oxytocin for induction or
      acceleration of labour. Episiotomy was done in 6 patients and instrumental
      delivery was performed in 3 patients. Gross haematuria immediately after delivery
      was the most common presentation, followed by urinary incontinence. Flank pain
      and fever were associated with ureteric injury and were delayed for few days.
      Urological injury should be suspected after vaginal delivery in females with
      previous caesarian section, if instrumental delivery is applied, and in patients
      with deep vaginal tears. The presence of gross haematuria, incontinence and flank
      pain should indicate full urological evaluation.

PMID- 9241542
TI  - Primary squamous cell carcinoma of the ureter presenting with urinoma. A case
      report.

PMID- 9241543
TI  - The outcome of urological findings in operated tethered cord patients.
AB  - We studied the urological aspects of the tethered cord syndrome before and after
      untethering. Presenting urological symptoms include incontinence in 10 (38%),
      voiding difficulty in 8 (30%), stool soilage in 7 (27%), pollakiuria in 8 (30%)
      and urgency and symptomatic urinary tract infection in 9 patients (34%). All
      patients had presacral skin lesion. In all cases cystometric study was done
      preoperatively and postoperatively. In this study, we noted that the overall
      clinical symptomatology and urodynamic parameters improved in 67.0% and 49.0%,
      respectively. Although no patient became normal after surgery, we found better
      improvement in patients treated promptly by neurosurgical intervention.

PMID- 9241544
TI  - Tumour in a giant bladder diverticulum: a case report and review of literature.
AB  - We report an unusual case of a transitional cell carcinoma arising in a bladder
      diverticulum presenting as a giant abdominal mass and acute urinary retention. We
      have reviewed the literature and discuss the aetiology, diagnosis, and treatment
      of tumours arising in vesical diverticula.

PMID- 9241545
TI  - Inverted papilloma of the urinary bladder: a case evaluated for malignant
      potential.
AB  - We report a case of inverted papilloma in the urinary bladder with special
      reference to its malignant potential. A 77-year-old male patient complaining of
      microhaematuria was subjected to cystoscopic examination, which showed a non
      papillary pedunculated tumour at the postero-lateral wall, and was treated with
      transurethral resection. The histological findings of the specimen were
      compatible with inverted papilloma of the urinary bladder, except for the
      presence of low grade dysplastic changes in the tumour nuclei. We revealed the
      malignant potential of this tumour, analyzing and evaluating nuclear DNA content,
      proliferating cell nuclear antigen (PCNA) as well as p53 expression.

PMID- 9241546
TI  - Perineal ileal conduit--cutaneous fistula.

PMID- 9241548
TI  - Dilutional hypocalcaemia from urological irrigating fluids.
AB  - A normal serum calcium concentration is essential for cardiovascular and muscular
      function. The hypocalcaemia-inducing potential of urological irrigating fluids
      was studied in 7 young men and in 10 prostatectomy patients. A total of 48
      intravenous infusions of 1,000 ml of various irrigating fluids showed
      consistently that dilution of the serum calcium concentration occurs. The
      magnitude of the dilution was in between that recorded for albumin and for
      sodium. The free calcium concentration, however, correlated closely with the
      serum sodium level. These results suggest that dilutional hypocalcaemia can be
      expected to coexist with hyponatraemia in patients who develop the transurethral
      resection syndrome.

PMID- 9241547
TI  - Effect of the alpha-1 adrenoceptor blocker on tissue norepinephrine contents in
      human benign prostatic hyperplasia.
AB  - To see the effect of the alpha-adrenergic blocking agent on tissue norepinephrine
      contents of the prostate, norepinephrine (NE) levels were investigated in
      patients with symptomatic benign prostatic hyperplasia (BPH). Morphometrical
      analyses were also performed to detect the differences in tissue composition.
      Nineteen patients were subdivided into two groups. Patients in Group 1 were given
      tamsulosin hydrochloride (0.2 mg/day) for at least 4 weeks before transurethral
      resection of the prostate (TURP), while patients in the control group (Group 2)
      underwent no previous treatment for BPH before TURP. Tissue NE contents were
      investigated by high performance liquid chromatography on a chip of the prostate
      obtained by TURP. These two groups were closely similar in age distribution,
      prostatic size, results of preoperative symptom scoring and relative proportion
      of smooth muscle component within the evaluated specimen. In the present series,
      tissue NE contents in these groups were not statistically different (p = 0.64).
      Chronic and acute administration of the alpha-1 antagonist did not apparently
      influence the tissue NE level in patients with BPH.

PMID- 9241549
TI  - Two cases of retrovesical haematoma following prostatic biopsy.
AB  - Prostatic biopsy is a definitive diagnostic method that should be used whenever a
      prostatic malignancy is suspected. Anatomically it can be done from the
      transrectal or perineal route. In two methods transrectal ultrasonography can be
      used as a helper tool. In this paper we present two cases of pelvic haematoma
      following prostatic biopsy that occasionally cause complications.

PMID- 9241550
TI  - Cyproterone acetate monotherapy in advanced prostatic carcinoma.
AB  - Cyproterone acetate was given as monotherapy to 18 patients with advanced
      prostatic carcinoma at a weekly dose of 300 mg. Progression was observed in all
      of the patients; median time to progression was 35 months and median survival
      time was 48 months. Partial response, stabilization, progression and exitus rates
      by years also showed favourable results, as compared with other forms of therapy
      in advanced prostatic carcinoma.

PMID- 9241551
TI  - Raised prostate-specific antigen in adenocarcinoma of the colon.
AB  - Serum prostate-specific antigen (PSA) values above 10 ng/ml are considered highly
      sensitive and specific for prostatic carcinoma in the absence of prostatic
      inflammation or trauma. However, in rare instances, non-prostatic malignancies
      have also been associated with raised serum PSA values. We have encountered a
      patient with increased serum PSA concentration measured by monoclonal antibody
      assay who had no evidence of prostatic malignant involvement, but suffered from
      colon cancer. Before operation for colon cancer his PSA was always over 30 ng/ml
      on several examinations. After total removal of colon cancer serum PSA level fell
      down to 1.2 ng/ml. Although immunohistochemical staining of colon cancer with
      monoclonal PSA antibody was not performed, some relationship between raised PSA
      and colon cancer is strongly suspected. Substances like serine protease which can
      cross-react with the PSA antibody might be produced by malignant tumour of non
      prostatic origin.

PMID- 9241552
TI  - Liposarcoma of the spermatic cord: a report of two cases.
AB  - Liposarcoma of the spermatic cord usually occurs as a painless slow growing
      scrotal swelling and can present with sudden enlargement of the mass. Recurrences
      are frequent, owing to incomplete surgical removal of the tumour.

PMID- 9241553
TI  - The importance of visual erotic stimulation in the differential diagnosis of
      erectile impotence.
AB  - In this study we aimed to determine the importance of visual erotic stimulation
      (VES) alone, and in combination with intracavernosal papaverine injection (ICPE)
      in the differential diagnosis of erectile impotence. Sixty-four patients with
      erection problems were investigated between June 1992 and January 1994. VES could
      be the first investigative method in the differential diagnosis of erectile
      impotence. This will help us in some groups of patients with psychogenic
      impotence to avoid the application and complications of ICPE. In patients with
      insufficient erections with VES alone, ICPE must be combined with VES in order to
      detect the causes of psychogenic erectile impotence more correctly.

PMID- 9241554
TI  - A case of primary giant calculus in female urethra.
AB  - Urinary calculus is rarely seen in the urethra and is usually encountered in men
      with urethral stricture or diverticulum. Primary urethral calculi are extremely
      rare in females. We describe a case of a giant urethral stone impacted in the
      urethra of a 103-year-old female.

PMID- 9241555
TI  - Distal hypospadias repair with meatal-based flaps on an outpatient basis.
AB  - We report the results of primary repairs that were performed on 52 consecutive
      patients with distal hypospadias as an outpatient procedure. A modified Mathieu
      repair with meatal-based vascularized flap was performed under 2.5 optical
      magnification using Scottring retractors, traction sutures, micro instruments and
      fine suture material. A total of 3 patients had complications that required
      reoperation (5.8%). One of these 3 complications was a urethrocutaneous fistula
      (1.9%). We found that the repair of distal hypospadias was successful with meatal
      based flap using contemporary finer approaches and equipment.

PMID- 9241556
TI  - Erythropoietin in patients with acute renal failure and continuous veno-venous
      haemofiltration.
AB  - Erythropoietin (Epo) is a glycoprotein hormone produced in the kidney in response
      to hypoxia or anaemia. In acute renal failure (ARF) anaemia also occurs and
      current opinion is that Epo production is depressed with inappropriately low
      plasma levels throughout the uraemic phase. Our study was designed to determine
      the excretion of Epo in patients with ARF. Fifty-nine ventilated patients were
      studied, 39 with ARF and continuous veno-venous haemofiltration therapy (group 1)
      and 13 patients with normal renal function who served as a control group (group
      2). All patients with ARF were anaemic and needed a mean transfusion of 0.6
      units/day. Values for vitamin B12, folic acid, serum iron and ferritin were
      normal. While patients with normal renal function had Epo values within the
      normal range, patients with ARF had significantly higher values at the onset of
      haemofiltration therapy. Mean Epo (mean +/- SEM) values on days 0-2 were 92.6 +/-
      11.7 mU/ml in group 1 and 16.5 +/- 6.4 mU/ml in group 2 (p < 0.0002). Epo levels
      declined in group 1 to 49 +/- 10.5 mU/ml on days 9 and 10 compared to 23 +/- 9.1
      mU/ml in group 2 (ns). These values were maintained until the end of the
      observation period. No differences were seen between oliguric and non-oliguric
      patients. Our data show that patients with ARF have increased Epo levels at the
      beginning of the disease with a strong tendency to decrease, suggesting that
      there might be inadequate Epo levels during the course of acute renal failure.

PMID- 9241557
TI  - 1.25(OH)2 cholecalciferol pulse therapy and the effects of different dialysis
      membranes on serum PTH levels of haemodialysis patients.
AB  - Either oral, intravenous or subcutaneous 1.25(OH)2 cholecalciferol is used in the
      therapy of hyperparathyroidism, which is a serious complication in patients on
      haemodialysis. We studied a total of 30 patients (10 women and 20 men) and
      divided them into two groups depending on the different types of dialysis
      membranes used. In the polysulfone group, mean age was 43.7 +/- 0.97 years and
      the average dialysis period lasted 29.9 +/- 1.23 months. For the 15 cases in
      which we used cuprophane membrane the mean age was 40.2 +/- 1.31 years and the
      average dialysis period lasted 16.2 +/- 0.86 months. The calcium level of the
      dialysate in both groups was 1.5 mmol/l. According to the study protocol, the
      determined oral calcitriol dose was 0.07 mg/kg and it was administered
      intermittently. After one month on high dose calcitriol therapy, treatment was
      continued with a maintenance dose of 0.03 mg/kg for a further six months. As a
      phosphate binding agent, daily 3 g calcium carbonate was administered. Before
      starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy,
      although the mean PTH level was 424.63 pg/ml and the mean serum alkaline
      phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH,
      alkaline phosphatase, ionized calcium, and total calcium remained significantly
      within normal limits as a result of the new therapy protocol applied. PTH and
      phosphorus clearance rates were compared in the patient groups in which different
      dialysis membranes had been used. PTH and phosphorus clearances were 15.2 +/- 3
      ml/min and 239.1 +/- 19.2 ml/min, respectively, in the polysulfone membrane
      group, and 1.1 +/- 0.3 ml/min and 112.8 +/- 9.88 ml/min, respectively, in the
      cuprophane membrane group (p < 0.05).

PMID- 9241558
TI  - Frontal lobes pathology and dementia. An appraisal of the contribution of
      Leonardo Bianchi.
AB  - This paper which was inspired by Leonardo Bianchi's work, published in English a
      hundred years ago, summarizes the main features of frontal dementias, with
      particular emphasis on Pick's Disease (PiD) and on Frontal Lobe Dementia (FLD).
      We intend to examine on one hand whether these behavioral changes follow
      pathology strictly limited to the frontal lobes and on the other hand whether
      these changes truly constitute a dementia. Currently available data suggest the
      following conclusions: 1) Lesions to the frontal lobes produce a dementia which
      is clearly different from the typical picture of Alzheimer's disease and which
      can be called a behavioral dementia. 2) The pathology of the so-called frontal
      dementias usually extends beyond the limits of the prefrontal cortex. 3)
      Executive functions classically thought to be related to frontal lobe structures
      are in fact associated with structures outside the frontal lobes, particularly in
      the telencephalic and limbic cortex. These findings in no way diminish the value
      of the work of Leonardo Bianchi. Rather, they strengthen it. We consider that the
      work of this great Neuroscientist remains highly relevant and that after 100
      years, it still represents the starting basis for further works and ideas.

PMID- 9241559
TI  - Vascular reactivity in middle cerebral artery and basilar artery by transcranial
      Doppler in normals subjects during hypoxia.
AB  - The anatomical and physiological differences between the carotid and
      vertebrobasilar circulations suggest the possibility of a different response to
      variations in systemic pO2. We evaluated cerebrovascular response (CR) in these
      two systems by monitoring variations in the blood flow velocities in the middle
      cerebral and basilar arteries during hypoxia. Eighteen healthy, non-smoking
      volunteers underwent transcranial Doppler study during a state of hypoxia
      obtained by means of the rebreathing method. Oxyhaemoglobin saturation (SaO2) was
      monitored using a pulsoxymeter in the 88-94% range. The cerebral blood flow
      velocity (BFV) was measured in the right middle cerebral artery (MCA) and the
      basilar artery (BA). Our findings indicate that the mean blood flow velocity
      (MFV) in the BA changes at a lower rate than that in the MCA during hypoxia.

PMID- 9241560
TI  - The first in vivo experience of the effects of the continuous intrathecal
      infusion of clonidine on the locus coeruleus in the regulation of cerebral blood
      flow: a TCD study.
AB  - This was a study of the action of continuous intrathecal clonidine infusion on
      the locus coeruleus in the regulation of cerebral blood flow (CBF) by means of a
      test of the activation of the locus coeruleus (cold pressure test, CPT). METHOD:
      The effects on CBF of intrathecal clonidine used for analgesic purposes in a
      patient with a chronic painful benign syndrome were studied by means of
      transcranial Doppler sonography (TCD) before and after administering the CPT.
      RESULTS: TCD with the infusion device activated revealed an increase in CBF
      velocities compared with those recorded when the device was inactivated. During
      CPT with the infusion device inactivated, TCD showed a decrease in CBF velocity:
      this decrease was less when the device was activated. CONCLUSIONS: Our results
      suggest that the intracerebral vascular responses induced by CPT and intrathecal
      clonidine infusion may be related to a sympathetic regulating mechanism of
      cerebral vascularization, possibly mediated by locus coeruleus.

PMID- 9241561
TI  - Neurophysiological classification of carpal tunnel syndrome: assessment of 600
      symptomatic hands.
AB  - Following the AAEM electrodiagnostic guidelines, we developed a
      neurophysiological classification of carpal tunnel syndrome (CTS). Six hundred
      hands with clinical CTS (mean age 51.4 yr., female/male ratio 5.5/1, right/left
      ratio 1.8/1) were prospectively evaluated and divided into six classes of
      severity only on the basis of median nerve electrodiagnostic findings: extreme
      CTS (EXT-absence of thenar motor responses), severe CTS (SEV-absence of sensory
      response and abnormal distal motor latency-DML), moderate CTS (MOD-abnormal digit
      wrist conduction and abnormal DML), mild CTS (MILD-abnormal digit wrist
      conduction and normal DML), minimal CTS (MIN-exclusive abnormal segmental and/or
      comparative study), and negative CTS (NEG-normal findings at all tests). Using
      this neurophysiological classification, the CTS groups appeared normally
      distributed (EXT 3% of cases, SEV 14%, MOD 36%, MILD 24%, MIN 21%, NEG 3%), and
      the age of patients and clinical findings appeared to be related to
      neurophysiological abnormalities. Significant differences in median
      neurophysiological parameters not included in the classification (such as palm
      wrist sensory conduction velocity) were observed in the different CTS groups. The
      analysis of the groups showed that: 1) the majority of advanced cases (SEV and
      EXT) occurred in older patients (60-80 years), 2) most of the milder cases (MIN
      and MILD) occurred in young female patients. The aim of this study was to
      standardise the neurophysiological evaluation of CTS.

PMID- 9241562
TI  - Platelet monoamine oxidase molecular activity in demented patients.
AB  - Blood platelet monoamine oxidase activity, as well as other platelet enzyme
      activities, have been studied in several neuropsychiatric disorders in an attempt
      to identify biochemical markers of altered brain function. In this study, we
      determined both total and molecular monoamine oxidase activity in platelets
      derived from demented patients, which showed significantly greater enzyme
      activity than those of the controls. It therefore seems that the high degree of
      monoamine oxidase activity depends on the increased intrinsic activity of
      individual enzyme molecules. A significant positive correlation was found between
      monoamine oxidase activity and the severity of illness, which suggests that
      monoamine oxidase activity may be a state-dependent marker of neurodegeneration.
      These findings are discussed with reference to the central nervous system
      biochemical abnormalities of demented subjects: it may be that Alzheimer-type
      dementia involves some central biochemical changes that are reflected in certain
      peripheral tissues (e.g. platelets), or a systemic derangement that also affects
      the brain.

PMID- 9241563
TI  - Immunological and endocrinological abnormalities in paraneoplastic disorders with
      involvement of the autonomic nervous system.
AB  - We report a series of four patients in whom the onset of systemic cancer was
      heralded by dysautonomic symptoms and a neurological non-metastatic complication
      mediated by immunological and endocrine factors. The series includes: a patient
      with acute leukaemia and autonomic sensory-motor polyradiculoneuropathy, a
      patient affected by colon carcinoma and autonomic neuropathy and limbic
      encephalitis, a patient with lung cancer and autonomic neuropathy and
      hypercalcaemic encephalopathy, a patient with small cell lung cancer associated
      with autonomic neuropathy in Lambert-Eaton Myasthenic Syndrome (LEMS) and
      syndrome of inappropriate ADH secretion (SIADH). We underline the prognostic
      importance and discuss the possible etiopathogenetic role of autonomic
      dysfunction, which is frequently associated with paraneoplastic neurologic
      syndromes of autoimmune and/or dysendocrine origin.

PMID- 9241564
TI  - Four-year follow-up of a case of acute multiple sclerosis of the Marburg type.
AB  - We describe the clinical course, treatment and magnetic resonance findings during
      a four-year follow-up of a patient with acute multiple sclerosis of the Marburg
      type, treated with steroid and mannitol therapy, who survived the first bout.
      Although the course of the disease was clinically indistinguishable from
      relapsing-remitting multiple sclerosis, our case was characterized by peculiar
      features. These included the need for protracted steroid therapy and the
      remarkable tendency of MRI lesions to resolve completely.

PMID- 9241565
TI  - Semantic amnesia without dementia: documentation of a case.
AB  - We described the case of a patient affected by a progressive semantic memory
      disorder associated with prevalent temporal lobe atrophy. This deficit seems to
      be "pure" in the sense that it has not been found to overlap with other cognitive
      deficits (intellectual, linguistic, perceptual, visuo-spatial etc.) for a long
      time. Furthermore, despite his impaired semantic knowledge, the autobiographical
      memory of the patient was largely intact. This case therefore represents a form
      of "semantic amnesia" without dementia, and supports the hypothesis that there is
      a partial distinction between "semantic" and "episodic" memory.

PMID- 9241566
TI  - Solitary cerebral metastasis from tumor of the testis: some observations about
      treatment in two cases.
AB  - The authors describe two cases of solitary cerebral metastasis from non
      seminatous germ cell tumors of the testis: in the first case, the histology was
      teratocarcinoma; in the second, it was embryonal carcinoma. Both patients
      underwent surgery, whole-brain radiotherapy and chemotherapy, and are still alive
      and disease-free after respectively 42 and 72 months. Although systemic
      metastasis from tumors of the testis are relatively common, they rarely involve
      the nervous system. A review of our cases and those reported in the literature
      shows that the outcome in these patients can be improved by the combined
      surgical, radiological and chemotherapeutic treatment of the metastasis.

PMID- 9241567
TI  - Cervical cord compression due to atypical primary neuroectodermal tumor (PNET):
      one-stage removal and combined cervical spine stabilization. Case report.
AB  - INTRODUCTION: The neuroectodermal tumor of bone constitutes a recently isolated
      neoplasm, which morphologically resembles the peripheral neuroepithelioma of soft
      tissue. The diagnosis is made by excluding readily classified small round cell
      neoplasms and then demonstrating the neural origin of the tumor by means of
      ultrastructural or immunocytochemical studies. CLINICAL CASE: We report a case of
      a primary neuroectodermal tumor (PNET) with atypical findings (primary cervical
      location, massive vertebral body infiltration and isolated neurological
      symptomatology). Total tumor removal was achieved by means of a one-stage three
      level laminectomy (partial C5, total C6-C7), C6 somatectomy, and combined
      anterior and posterior cervical spinal instrumentation and fusion. CONCLUSIONS:
      Our case presents three peculiar features: 1) isolated myelopathic symptomatology
      (first case described); 2) primary isolated massive vertebral cervical
      involvement with intraspinal epidural extension (first case described); 3) one
      stage tumor resection, fusion and instrumentation. Since radiation therapy causes
      tumor shrinkage but is not curative, radical removal is mandatory even with
      complex instrumentation procedures.

PMID- 9241568
TI  - Genetic heterogeneity in autosomal dominant nocturnal frontal lobe epilepsy.

PMID- 9241569
TI  - Brofaromine versus imipramine in in-patients with major depression--a controlled
      trial.
AB  - Brofaromine is a selective and reversible inhibitor of monoamine oxidase A. The
      efficacy and safety of this compound as compared with tricyclic antidepressants,
      classical monoamine oxidase inhibitors and placebo has been demonstrated in
      several clinical trials. The present 6-week, double-blind, randomized trial
      compared brofaromine with imipramine in in-patients with major depression.
      Brofaromine was as effective as imipramine in the treatment of major depression,
      but exhibited a different side-effect profile, in particular lacking the
      anticholinergic and certain cardiovascular side-effects of the tricyclic
      imipramine, but more likely to induce sleep disturbances. In this study, in
      patients were examined, since the majority of controlled clinical trials on
      depressed patients conducted so far have focused on the evaluation of out
      patients. If one assumes that a different degree of severity of depression exists
      between these two patient groups, then the results of those trials conducted on
      out-patients cannot readily be transferred to in-patients.

PMID- 9241570
TI  - Serotonergic autoreceptor blockade in the reduction of antidepressant latency:
      personality variables and response to paroxetine and pindolol.
AB  - No antidepressant currently in use exerts a significant antidepressant effect for
      at least two to three weeks after the patient starts taking it. Open studies
      suggest that, for selective serotonergic re-uptake inhibitor (SSRI)
      antidepressants, this latency may be reduced when the drug is taken with the
      5HT1A receptor blocker pindolol. We have undertaken a randomised, placebo
      controlled, double blind trial of augmentation of the selective SSRI
      antidepressant paroxetine in combination with pindolol. All our patients (n = 54;
      mean age 36 [range 19-65]) met criteria for major depression and received a
      standard dose (20 mg o.d.) of paroxetine plus, randomly, either pindolol (2.5 mg
      t.d.s.) or placebo for six weeks. We examined personality variables in 48
      consecutive subjects according to a short version (TCI-125) of Cloninger et al's
      self-rated Temperament and Character Inventory (Cloninger et al., 1994) and
      correlated the results with clinical responses in the trial. The results suggest
      that personality can influence clinical outcome. After the double blind period
      patients were offered paroxetine 20 mg or 40 mg for up to 6 months. Twenty-six
      patients took this up. The results suggest that high scores in the temperament
      dimension of Reward Dependence and low scores in the temperament dimension of
      Harm Avoidance had a better outcome at 6 weeks. Patients who had received
      paroxetine and pindolol during the trial and who reported high Novelty Seeking
      and low Harm Avoidance scores had a better outcome at 6 weeks and 6 months. We
      suggest that temperament factors may influence outcome of antidepressant
      treatment.

PMID- 9241571
TI  - Non-verbal behavioral interactions of depressed patients with partners and
      strangers: the role of behavioral social support and involvement in depression
      persistence.
AB  - Excessive support seeking and lack of receiving social support have been
      associated with depression onset and unfavorable course of depression. It has
      been assumed that social support is effected by observable behaviors that express
      involvement. Twenty-five patients with major depression were studied during a
      social interaction with their partner and a similar interaction, with a stranger,
      matched on the sex and age of the partner. We anticipated that (1) partners would
      display less involvement behaviors to the depressed patients than would strangers
      and that (2) lack of involvement would predict an unfavorable course of
      depression, as assessed for depression remission within 6 months of admission.
      The social interactions, conducted at admission, were videotaped and the
      behaviors were assessed by ethological methods. The frequency and duration of
      behavioral elements were associated on the basis of statistical criteria into
      behavioral factors. Certain factors were supposed to express (lack of)
      involvement during an interaction. In the patient-partner interaction it was
      found that both participants displayed lower levels of involvement as compared to
      the patient-stranger interaction. The patients' low involvement was reflected by
      less Speech, less Eagerness (yes-nodding and no-shaking), less Speaking Effort
      (head movements, looking and gesturing during speech) and more Active Listening
      (intense touching of one's own body and head movements during listening). The
      partners' low involvement was also expressed by less Speech and more Active
      Listening, together with less Encouragement (yes-nodding and 'um-hum'-ing during
      listening). In addition, the partners displayed less Speech to patients who did
      not remit within 6 months, whereas patients and strangers behaviors were not
      related to depression remission. These findings supported our anticipations and
      the findings are related back to data on social support, involvement and to
      previous human ethological studies on depression.

PMID- 9241572
TI  - The influence of seasonal change on suicidal behaviour in Italy.
AB  - The seasonal variance of suicides and attempted suicides in Italy from 1974 to
      1994 has been studied to determine the extent and the nature of the seasonal
      influence on suicidal behaviour. The relationship between some climatic factors
      and suicide and attempted suicide rates has also been analyzed. A significant
      effect of seasonal change on suicidal behavior, with a clear peak in spring has
      been detected (ANOVA: df = 3/248, F = 5.875, p = 0.0007 for suicide; df = 3/248,
      F = 6.198, p = 0.0004 for attempted suicide), with a greater seasonal effect on
      males than females. The monthly distribution of suicide deaths and of attempted
      suicides follows a significant direct relationship with exposure to sun, and an
      inverse relationship with rainfall levels. So, one of the possible explanations
      for the effect of seasonal change on suicidal behaviour could be the changing
      seasonal climate. The complex influence of seasonal climate on human biological
      rhythms, particularly on 5-HT (serotonin) related functions, together with its
      effects on sociorelational habits, should be considered for suicide prevention.

PMID- 9241573
TI  - Problems in validating endogenous depression in the Arab culture by contemporary
      diagnostic criteria.
AB  - This study highlights the difficulties that may be encountered in attempting to
      apply the clinical construct of endogenous depression derived from western
      studies to depressed Arab patients. The agreement between 4 operational systems
      on the diagnosis of endogenous (melancholic) depression is explored in 100
      patients with primary depressive disorder in Al-Ain, United Arab Emirates. The
      symptom characteristics of the 61 patients in whom all diagnostic systems agreed
      are then described quantitatively and qualitatively. Subjects were evaluated by
      the Newcastle scale, Hamilton's 21 item depression scale, global assessment of
      functioning scale, and the operational criteria of the diagnostic systems used.
      Diagnosis of endogenicity was derived by computer according to the respective
      criteria. The agreement between DSM-IV, ICD-10, and RDC criteria is moderately
      high (0.72). When the Newcastle Index is included, it is only moderate (0.58).
      Disagreements are related to differences in diagnostic criteria. Small
      differences affect concordance appreciably. DSM-IV agreed with a majority of
      external validators, differentiating a more homogeneous groups of patients. In
      the present study, endogenous depression identified by western criteria, was less
      likely to manifest by guilt feelings, a distinct quality of mood, and loss of
      libido. The descriptions of patients reveal that the mood component of depression
      is expressed differently, somatic metaphors are used frequently to express
      distress, religious elements influence the expression of symptoms, and depression
      may manifest in behaviours not directly indicative of the disorder. Endogenous
      depression may be identified in the Arab culture, but considerable variation in
      its component symptom frequencies and mode of expression needs to be taken in
      consideration for defining it in terms appropriate to the culture.

PMID- 9241574
TI  - Personality traits of Japanese patients in remission from an episode of primary
      unipolar depression.
AB  - Personality traits were assessed by means of the Munich Personality Test (MPT) in
      75 Japanese subjects, 27 patients in remission from an episode of moderate to
      severe primary unipolar depression, with melancholic features during one episode
      or more of the disorder, in 24 patients in remission from other non-organic
      mental disorders and in 24 healthy controls. Compared with healthy controls,
      unipolar depressives displayed decreased Frustration Tolerance and elevated
      Rigidity as well as a stronger Orientation towards Social Norms. No significant
      difference was found between patients in remission from either unipolar
      depression or other mental disorders. However, the increase in Rigidity in
      comparison with healthy subjects was significant in the depressives only whereas
      the other patients, in contrast to the depressives, had significantly lower
      scores in Extraversion than the healthy subjects. Our results in Japanese
      patients are similar to findings of previous German studies, including two high
      risk studies, in which the same assessment instrument was used. This suggests
      that, beyond cultural differences, Rigidity, possibly in combination with a
      strong Orientation towards Social Norms and a reduced Frustration Tolerance, is a
      stable vulnerability marker for at least the more severe forms of primary
      unipolar depression.

PMID- 9241575
TI  - Autosomal recessive inheritance of affective disorders in families of responders
      to lithium prophylaxis?
AB  - In this paper we report the results of a study of the mode of inheritance in
      affective disorders responsive to lithium. Earlier we described a series of 71
      families in which the genetic transmission was compatible with a single-gene
      model. We have now carried out an independent replication study on 25 newly
      recruited families in a different geographical location. The autosomal recessive
      model from our original study could not be rejected with the new data. In a
      subsequent analysis of the pooled sample of 96 families, a recessive model with a
      common predisposing allele (q = 0.16) and sex-specific penetrance (0.35 in males,
      0.66 in females) fitted the data best. On the other hand, X-chromosome and
      polygenic models could be rejected. The finding of a major-gene effect represents
      a specific hypothesis that can be tested by molecular genetic techniques.

PMID- 9241577
TI  - The differential effects of mood on patients' ratings of life quality and
      satisfaction with their care.
AB  - The recent directives to improve both the quality and the efficiency of mental
      health service delivery systems have emphasized the need for evidence based
      treatment efficacy data, yet recent evidence suggests that quality of life data
      may be confounded with psychiatric symptomatology. The objective of the current
      inquiry was to determine whether responses to patient satisfaction measures are
      equally effected by mood-congruent response bias. Thirty-seven patients from a
      mood disorders clinic in an urban acute care hospital were asked to rate their
      current mood, satisfaction with their care, and quality of life. While patient
      rating of mood were highly correlated with specific quality of life scales and
      predicted 21% of the variance in global quality ratings, the more objective
      satisfaction indicators were not. For the clinician, these data suggest that
      clinically depressed patients may view their support system and care givers in
      negative or biased perspective.

PMID- 9241576
TI  - Predictors of service utilization in veterans with bipolar disorder: a
      prospective study.
AB  - This study prospectively followed 103 bipolar patients enrolled in a VA treatment
      program for 1 year. Mental health service utilization was recorded and aggregated
      using the VA Cost Distribution Report. We hypothesized that previously reported
      predictors of disease severity would also predict service utilization, and that
      several other predictors of service utilization might also be identified.
      Analyses indicated that only the presence of a major affective episode at clinic
      intake and a recalled history of childhood physical abuse predicted mental health
      service utilization. Contrary to expectations, previously reported predictors of
      disease severity were not significant predictors. Implications for the study of
      economic outcome are discussed. In particular, we propose that economic outcome
      is a complex function of both patient and system factors, rather than simply
      being passively driven by disease severity.

PMID- 9241578
TI  - Conduct disorder with and without mania in a referred sample of ADHD children.
AB  - OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD
      could be distinguished from one another in their patterns of familiality,
      adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls
      at baseline and 4 years later using assessments from multiple domains. We
      compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders
      on psychiatric outcomes at a 4-year follow-up, familial psychopathology and
      psychosocial functioning. RESULTS: We found that ADHD children with both
      disorders had higher familial and personal risk for mood disorders than those
      with CD only, who had a higher personal risk for antisocial personality disorder.
      Among ADHD probands, having both CD and BPD was associated with poorer
      functioning and an increased risk for psychiatric hospitalization. DISCUSSION:
      Although preliminary, our findings suggest that the distinction between dysphoric
      and non-dysphoric CD may be clinically meaningful. If confirmed, our findings
      could have important diagnostic and therapeutic implications for the management
      of antisocial youth.

PMID- 9241579
TI  - Major depressive disorder, depressive symptoms, and bilateral hearing loss in
      hispanic adults.
AB  - Studies in non-Hispanic whites have documented higher rates of hearing loss in
      adults with depression versus those without depression. Data from the Hispanic
      Health and Nutrition Examination Survey were used to investigate associations
      between depression and bilateral hearing loss in Cuban-American, Mexican
      American, and Puerto Rican adults 20-74 years of age. Pure tone thresholds were
      calculated by averaging thresholds obtained at 500, 1000, and 2000 Hz separately
      for each ear. Hearing loss was defined as bilateral pure tone average threshold
      levels greater than 25 db. Lifetime history of a major depressive episode was
      assessed by the Diagnostic Interview Schedule, and depressive symptoms were
      assessed by the Center for Epidemiologic Studies Depression Schedule. Prevalence
      of overall hearing loss was consistently lower in Hispanics with a history of
      major depressive disorder than among those without such a history. Odds of
      hearing impairment was significantly greater among Puerto-Ricans reporting more
      depressive symptoms versus fewer symptoms. However, no such associations were
      found among Mexican-Americans or Cuban-Americans. In conclusion, despite the
      findings in Puerto Ricans with depressive symptoms short of major depression,
      hearing impaired Hispanics overall do not appear at increased risk of major
      depressive disorder.

PMID- 9241581
TI  - The failure of 'adult' interventions with adolescent depression: what does it
      mean for theory, research and practice?
AB  - The literature on the biological and phenomenologic presentation of major
      depressive disorder (MDD) in adolescents is reviewed and compared with that of
      depressed adults. Biological and psychosocial treatment approaches with adults
      and adolescents are then contrasted and the applicability of adult interventions
      to adolescents is examined. Some biological, cognitive, and experiential
      differences between adult and adolescent MDD may have treatment implications
      which have not yet been adequately addressed in the field. No effective
      treatments for adolescent MDD have, as yet, been developed or empirically tested.
      Based upon the results of this review, suggestions are made for the direction of
      future research.

PMID- 9241582
TI  - Encapsulation of mammalian cells into synthetic polymer membranes using least
      toxic solvents.
AB  - Immunoisolation, that is, enclosure of cells within a semipermeable membrane to
      protect them from immunological rejection, may enable the transplantation of
      cells without use of immunosuppressive drugs. Therefore, in addition to naturally
      occurring ionic polymers, several synthetic nonionic polymers which can form
      dense and strong membranes in water have been studied as materials for
      immunoisolation. However, such nonionic polymers are required to be soluble in
      organic solvents which are mostly cytotoxic. In this report we describe enclosure
      of insulin-releasing cells into water-insoluble poly(2-hydroxyethyl methacrylate)
      and poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) membranes using X
      ray contrast medium as a solvent without use of any special apparatus. The
      contrast medium employed in our study is iopamidol aqueous solution. Insulin
      release was observed for 1 months when insulin-releasing cells were encapsulated
      into these membranes. The permeability of five solutes through the membranes
      prepared from the iopamidol aqueous solution was also studied to determine their
      potential immunoisolative efficacy.

PMID- 9241580
TI  - Exploring the TPQ as a possible predictor of antidepressant response to
      nefazodone in a large multi-site study.
AB  - Subjects in the midst of a major depressive episode completed the Tridimensional
      Personality Questionnaire (TPQ) prior to beginning an open trial of nefazodone. A
      multiple regression analysis was used to further examine the finding of Joyce et
      al. (1994; Temperament predicts clomipramine and desipramine response in major
      depression, J. Affect. Disord. 30 (1994) 35-46) that a model involving TPQ Reward
      Dependence and Harm Avoidance scores, and their interaction, significantly
      predicted treatment response. The model was found to have significant predictive
      value (R2 = 0.011, P = 0.0053), but to account for a trivial 1.1% of the
      variance. Individuals with high Reward Dependence scores had a significantly
      lower response rate when response was defined as a 60% reduction from baseline
      HAM-D score. Although the clinical utility of the present findings is uncertain,
      this line of investigation attempting to link temperament to pharmacological
      response represents a potentially useful future strategy.

PMID- 9241583
TI  - In vitro study of enzymatic degradation of biological tissues fixed by
      glutaraldehyde or epoxy compound.
AB  - The study, using bacterial collagenase, was to investigate the changes in
      characteristics of a collagen-rich tissue, porcine pericardium, fixed by
      glutaraldehyde or epoxy compound (ethylene glycol diglycidyl ether) during the
      course of degradation. Fresh porcine pericardium was used as a control. During
      degradation, the heat released by the reaction of collagenase with a test sample
      was monitored by a highly sensitive microcalorimeter. Also, the degree of
      degradation of each test sample was determined by measuring its increment in free
      amino group content and changes in denaturation temperature and tensile strength.
      Microcalorimetric analysis of collagenase degradation of fresh, epoxy-fixed, and
      glutaraldehyde-fixed tissues revealed that the heat released during degradation
      correlates well with the degree of tissue degraded. The cleaving of peptide bonds
      in biological tissue by collagenase degradation may increase its free amino group
      content and reduce its denaturation temperature and tensile strength. It was
      noted that the fresh tissue cannot resist bacterial collagenase degradation,
      while the glutaraldehyde-fixed tissue had a relatively better resistance to
      degradation than its epoxy-fixed counterpart.

PMID- 9241584
TI  - Development of new wound dressing composed of spongy collagen sheet containing
      dibutyryl cyclic AMP.
AB  - Although cyclic AMP has been considered to regulate cell proliferation, the
      mechanism of this function is largely unknown. Recent studies suggest that cyclic
      AMP promotes the proliferation of skin cells in a dose-dependent manner. An
      ointment containing dibutyryl cyclic AMP has been used in the treatment of skin
      ulcers and found to be effective in promoting tissue repair. To search more
      efficacious wound management, the authors developed a new wound dressing composed
      of a spongy atelo-collagen sheet containing dibutyryl cyclic AMP. This wound
      dressing was evaluated in two types of animal tests. One is the application of
      the wound dressing to a full-thickness skin defect in order to evaluate the
      granulation tissue formation and the wound size reduction. The wound dressing was
      found to promote the granulation tissue formation and naturally reduce the wound
      size. The other test was the application of the wound dressing to the full
      thickness skin defect, leaving behind a skin island in a central portion, in
      order to evaluate the epithelialization. This skin island left in a full
      thickness skin defect was extremely enlarged. The enlargement of the skin island
      seems to be related to the epithelialization from the margin of the skin island
      as well as by the expansion of a skin island induced by contraction of the
      developed granulation tissue in the surrounding wound area. These results suggest
      that an atelo-collagen spongy sheet containing dibutyryl cyclic AMP is effective
      in promoting the granulation tissue formation and epithelialization.

PMID- 9241585
TI  - Synthesis of silane coupling agents containing fluorocarbon chain and
      applications to dentistry: plaque-controlling surface modifiers.
AB  - Silane coupling agents containing a fluorocarbon chain were prepared in high
      yields. It was found that silanes can be useful modifiers of the surfaces of
      glass, metals, and resin composites for dental use. The silane coupling agent
      CF3(CF2)9CH2CH2Si(OCH3)3 was the best modifier of these surfaces in terms of
      water and oil repellency. Colorants and experimental bacterial plaque detached
      much more easily from, and adhered less well to, surfaces modified with this
      silane coupling agent compared with unmodified surfaces. The surfaces of four
      teeth of a denture were modified with this silane coupling agent by spreading the
      agent on the surfaces with a small brush followed by brief drying with a hair
      drier. The modified tooth surfaces of the denture, which was worn for four months
      in a heavy smoker's oral cavity, were more stain-resistant than the unmodified
      tooth surfaces. It is expected that silane coupling agents containing a
      fluorocarbon chain will be surface modifiers for enhancement of oral health.

PMID- 9241586
TI  - Development of a semisynthetic cheese medium for fungi using chemometric methods.
AB  - The growth, color formation, and mycotoxin production of six cheese-related fungi
      were studied on nine types of natural cheeses and 24 semisynthetic cheese media
      and compared using principal component analysis. The semisynthetic cheese media
      contained various amounts of Ca, K, Mg, Na, P, Fe, Cu, Zn, lactate, lactose, and
      casein. A robust well-defined and easily prepared semisynthetic cheese medium was
      developed for Penicillium commune, the most frequently occurring contaminant on
      semihard cheese. Growth experiments on the medium were repeatable and
      reproducible. The medium was also suitable for Penicillium camemberti. The medium
      had the following composition: 100 g of casein, 8.3 g of 90% lactate, 7.9 g of
      lactose, 7.3 g of CaCl2.2H2O, 2.6 g of MgSO4.7H2O, 26.0 g of NaCl, 20 g of agar,
      0.025 g of FeSO4.7H2O, 0.004 g of CuSO4.5H2O, and water to a total weight of 1
      kg. The semisynthetic cheese medium was less suitable for Penicillium roqueforti,
      Penicillium discolor, Penicillium verrucosum, and Aspergillus versicolor.
      However, another semisynthetic cheese medium could be recommended for P.
      roqueforti and P. discolor. That medium had higher contents of P (5000 ppm,
      wt/wt), K (5000 ppm), and Zn (50 ppm) and lower contents of Na (2700 ppm), Fe (1
      ppm), Cu (0.1 ppm), and casein (1%).

PMID- 9241587
TI  - Digoxigenin-labeled deoxyribonucleic acid probes for the enumeration of
      bifidobacteria in fecal samples.
AB  - The numbers of bifidobacteria in fecal samples were specifically determined by
      colony hybridization with the mixture of digoxigenin-labeled DNA probes that were
      prepared from whole chromosomal DNA of Bifidobacterium longum 6001 and
      Bifidobacterium adolescentis 6003. These DNA probes strongly hybridized with DNA
      of B. longum, B. adolescentis, Bifidobacterium breve, Bifidobacterium suis,
      Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium angulatum, and
      Bifidobacterium animalis. Detectable positive signals with DNA of Bifidobacterium
      pseudolongum ssp. pseudolongum, Bifidobacterium catenulatum, and Bifidobacterium
      thermophilum were also found after hybridization. When dot-blot hybridization was
      performed with whole cells of 47 reference strains containing 11 species (16
      strains) of bifidobacteria, all of the bifidobacteria tested could be
      specifically detected by using these DNA probes; Lactobacillus fermentum JCM
      1173, however, showed a slight nonspecific signal. The counts of bifidobacteria
      by colony hybridization in the fecal samples of four of the five subjects were
      the same as the counts that were obtained by the conventional method using BL
      agar medium. Furthermore, no significant difference existed in the number of
      bifidobacteria that were determined by either method.

PMID- 9241588
TI  - Physiological changes at parturition and their relationship to metabolic
      disorders.
AB  - Most of the metabolic diseases of dairy cows-milk fever, ketosis, retained
      placenta, and displacement of the abomasum-occur within the first 2 wk of
      lactation. The etiology of many of those metabolic diseases that are not
      clinically apparent during the first 2 wk of lactation, such as laminitis, can be
      traced back to insults that occurred during early lactation. In addition to
      metabolic disease, the overwhelming majority of infectious disease, in particular
      mastitis, becomes clinically apparent during the first 2 wk of lactation. Three
      basic physiological functions must be maintained during the periparturient period
      if disease is to be avoided: adaptation of the rumen to lactation diets that are
      high in energy density, maintenance of normocalcemia, and maintenance of a strong
      immune system. The incidence of both metabolic and infectious diseases is greatly
      increased whenever one or more of these physiological functions are impaired.
      This paper discusses the etiological role of each of these factors in the
      development of common diseases encountered during the periparturient period.

PMID- 9241589
TI  - Strategies for preventing milk fever in dairy cattle.
AB  - Milk fever is a complex metabolic disorder that occurs at the onset of lactation.
      Clinical symptoms of this disease include inappetence, tetany, inhibition of
      urination and defecation, lateral recumbency, and eventual coma and death if left
      untreated. The hallmark of this disease is severe hypocalcemia, which probably
      accounts for most of the clinical signs associated with a milk fever episode.
      Several factors have been consistently associated with increased incidence of
      milk fever, including parturition and initiation of lactation, advancing age,
      breed, and diet. Of the various methods used in attempts to control the disease,
      the most progress has been made in dietary management. Until recently, most
      attention has focused on manipulating the levels of dietary calcium to control
      milk fever incidence; results, however, have been inconsistent, except for those
      diets containing very low (8 to 10 g/d) concentrations of Ca. During the past
      decade, there has been renewed interest and research in the use of dietary anions
      (Cl- and SO4(2-) in controlling milk fever. An outgrowth of this research has
      been the surprising realization that dietary K is significant (perhaps more
      significant than Ca) in determining the susceptibility of dairy cows to milk
      fever. This knowledge has expanded the understanding of the pathogenesis of milk
      fever and has focused attention on research designed to study methods for
      neutralizing the detrimental effects of dietary K excess on periparturient animal
      health. This report discusses various practical strategies and potential research
      areas for managing the dietary forage components to minimize the effects of K on
      milk fever incidence.

PMID- 9241590
TI  - Effect of atropine on milk protein yield by dairy cows with different beta
      lactoglobulin phenotypes.
AB  - The objective of this study was to determine the response of individual milk
      proteins to a reduction in amino acid (AA) availability induced by atropine and
      to determine whether the response was different in cows with different beta
      lactoglobulin (LG) phenotypes. Six cows that were homozygous for the A variant of
      beta-LG and six cows that were homozygous for the B variant of beta-LG were each
      given a single subcutaneous injection of saline or 20 mg of atropine. In both
      groups of cows, atropine decreased milk yield by 30% and reduced the
      concentration of alpha-lactalbumin (LA) by 25 to 30% at 8 h following injection.
      Eight hours after atropine injection, yield of beta-LG was 41% lower than it was
      following saline injection, and yield of beta-casein (CN) after atropine
      injection declined 16% relative to saline. Concentrations of BSA and the ratio of
      gamma-CN to beta-CN, which reflects plasmin activity in milk, were significantly
      increased after administration of atropine. Although the response to atropine
      tended to be more pronounced in cows that were homozygous for beta-LG B, they
      were not significantly different from the response of cows that were homozygous
      for beta-LG B, they were not significantly different from the response of cows
      that were homozygous for beta-LG A. The differential response of individual
      proteins to a reduction in AA concentrations in whole blood suggested that
      susceptibility to restriction in substrate availability differed for individual
      proteins. The concentration of lactose in plasma did not change, which implied
      that the integrity of the mammary epithelial barrier was not compromised when AA
      derived from blood were diminished. The consistent concentration of lactose
      combined with the minimal increase in total yield of BSA in milk following
      atropine treatment indicated that the increased concentration in milk of proteins
      derived from serum was due to the concentrating effect of lower milk volume.

PMID- 9241591
TI  - Reduced fertility associated with low progesterone postbreeding and increased
      milk urea nitrogen in lactating cows.
AB  - The primary objectives of this study were to determine whether a delay in the
      onset of the luteal phase, or high milk urea nitrogen at breeding, or both were
      associated with failure of pregnancy early in gestation. Milk samples were
      collected twice daily from cows in a single herd during the week following
      breeding; single samples were collected on d 14 and 21 postbreeding. Progesterone
      was measured in all samples, and a total of 156 sample sets was used. The
      progesterone data combined with results from pregnancy examinations were used to
      distribute the cows into three groups: 1) pregnant, 2) nonpregnant with a low
      concentration (< 2 ng/ml) of progesterone on d 21, and 3) nonpregnant with a high
      concentration (> or = 2 ng/ml) of progesterone on d 21. The interestrous interval
      for cows in group 3 was longer than that for cows in group 2. Beginning 4.5 d
      after breeding, pregnant cows had higher concentrations of progesterone than did
      cows in group 3. Pregnant cows also had higher concentrations of progesterone
      than did all open cows on d 14 and 21. The onset of the luteal phase was earlier
      in pregnant cows than it was in cows in group 3. Milk urea nitrogen at breeding
      was similar in pregnant cows and in cows in group 3, but was higher in cows in
      group 2. Increased milk urea nitrogen was also statistically associated with
      decreased fertility. We propose that the cows in group 3 likely had embryos that
      initiated pregnancy recognition and prolonged luteal function, but these embryos
      were compromised by suboptimal exposure to progesterone early in development.

PMID- 9241592
TI  - Comparison of mechanistic rumen models on mathematical formulation of
      extramicrobial and microbial processes.
AB  - This study investigated the consequences of differences in applied concepts and
      individual mathematical formulations on steady-state behavior of three important
      mechanistic rumen models. In the models of Baldwin et al. (2) and Danfaer (6),
      the formulation of passage rate, nondietary inputs, defined rumen substrate
      pools, absorption rates, degradation rates, molecular weights, parameterization
      of VFA production, and physical compartmentalization were sequentially exchanged
      for the formulation of the model of Dijkstra et al. (9). Most of these
      adaptations had a considerable influence on model behavior, indicating large
      qualitative differences in formulation and sensitivity to concept choice. Because
      microbial substrate environments were similar after all adaptations, the
      microbial mechanisms could be compared objectively without being concealed by
      differences in extramicrobial formulation. None of the microbial functions were
      altered except for substrate degradation, which gave rise to a similar rate of
      substrate entrance to soluble rumen pools that are available for microbial
      utilization. Large differences remained in microbial functions of substrate
      fermentation, substrate incorporation, and microbial synthesis. Differences in
      extramicrobial rumen functions and microbial mechanisms had important
      consequences for simulated nutrient outputs from the rumen, illustrating the
      necessity for further validation of individual formulations.

PMID- 9241593
TI  - Abomasal infusion of glucose and fat--effect on digestion, production, and
      ovarian and uterine functions of cows.
AB  - Four ruminally cannulated lactating dairy cows, arranged in a 4 x 4 Latin square
      design, were infused abomasally with 1) water (control), 2) 1 kg/d of glucose, 3)
      0.45 kg/d of tallow, and 4) 0.45 kg/d of yellow grease. Cows were synchronized
      for estrus within each 35-d period by injection of a GnRH agonist followed 7 d
      later by an injection of PGF2 alpha. Dry matter intake was not affected by
      infusates. Apparent digestibility of total fatty acids was greater for cows
      receiving the fat infusions relative to those receiving the glucose infusion and
      tended to increase for cows receiving the yellow grease infusion compared with
      those receiving the tallow infusion. Energy infusions decreased apparent acid
      detergent fiber digestibility compared with effects of the control infusion. Fat
      infusions tended to increase milk fat percentage and decrease the energy status
      of cows relative to the glucose infusion. The feed efficiency was greater for
      cows receiving fat infusions than for those receiving the glucose infusion and
      was greater for cows receiving the yellow grease infusion than for those
      receiving the tallow infusion. Plasma progesterone concentration peaked higher
      during the estrous cycle for cows infused with fat than for those infused with
      glucose. Mean growth rate and maximum size of the first wave dominant follicle
      were greater with tallow than with yellow grease. During the period of infusion
      of yellow grease and afterward, release of 13,14-dihydro-15-keto-PGF2 alpha in
      response to an injection of oxytocin on d 15 of the estrous cycle was attenuated.

PMID- 9241594
TI  - Response of lactating cows to supplemental unsaturated fat and niacin.
AB  - Responses to supplemental unsaturated fat or niacin in a 2 x 2 factorial
      arrangement were evaluated with 16 lactating Holstein cows in a replicated Latin
      square with 4-wk periods. Total mixed diets contained (dry matter basis) 25%
      alfalfa hay, 25% corn silage, and 50% concentrate mixture. Diets were the control
      or the control supplemented with unsaturated fat (3% of dry matter of the total
      mixed diet from extruded soybeans, which replaced soybean meal and portions of
      the corn and barley in other concentrates), niacin (12 g/d of nicotinic acid), or
      both unsaturated fat and niacin. Milk production increased with the addition of
      fat but was unaffected by the addition of niacin (31.9, 35.1, 32.2, and 35.5
      kg/d). Milk fat percentages were unaffected by the addition of fat or niacin to
      the diet, but proportions of both unsaturated and long-chain fatty acids
      increased with supplemental fat and were further increased with niacin in
      addition to fat; however, niacin was ineffective without fat. Milk protein
      percentages were lower with supplemental fat but were unaffected by niacin. Dry
      matter intake; ruminal volatile fatty acids, pH, and ammonia; serum urea; plasma
      glucose; and plasma amino acids were unaffected by supplemental fat or niacin.
      The first-limiting amino acid for milk protein synthesis was lysine for control
      diets and methionine for diets with supplemental fat. Supplementation of the diet
      with an unsaturated fat source increased milk production and the proportion of
      unsaturated fatty acids in milk, but niacin supplementation had no substantial
      influence on milk production and only a minor influence on milk fatty acid
      content.

PMID- 9241595
TI  - Digestion and passage kinetics of forage fiber in dairy cows as affected by fiber
      free concentrate in the diet.
AB  - Four ruminally and duodenally cannulated Holstein cows in early lactation were
      fed alfalfa [47% neutral detergent fiber (NDF)] or timothy silage (49% NDF) for
      ad libitum intake in a 4 x 4 Latin square experiment. Forages were supplemented
      with 8 or 12 kg/d of an essentially fiber-free concentrate to study digestion and
      passage kinetics of forage fiber in high producing dairy cows. Fractional
      digestion and passage rates of NDF in the rumen were derived from ruminal pool
      sizes. Alfalfa had a potentially digestible NDF fraction with a faster rate of
      digestion but a larger indigestible NDF fraction and, consequently, higher
      physical fill in the rumen than did timothy. However, dry matter intake did not
      differ between forages, primarily because of the higher fractional passage rates
      of alfalfa NDF. Although dry matter intake was 23.2 kg/d, fractional passage
      rates of forage NDF were generally lower than those usually assumed. Fractional
      rates of NDF digestion decreased equally for both forages as concentrate in the
      diet increased, but diets with alfalfa forage had the smallest quantitative
      reduction because of the markedly smaller ruminal pool size of potentially
      digestible NDF. The fractional passage rate of NDF decreased as concentrate in
      the diet increased for diets containing alfalfa but did not change for diets
      containing timothy. Consequently, as concentrate in the diet increased,
      digestibilities of NDF in the rumen and whole tract increased with alfalfa and
      decreased with timothy. Results suggest that fiber-free concentrate is useful
      when digestion and passage kinetics of specific forage fibers are being measured
      in high producing dairy cows.

PMID- 9241596
TI  - Whole cottonseeds or a combination of soybeans and soybeans hulls in the diets of
      lactating dairy cows.
AB  - Whole raw soybeans and soybean hulls were evaluated as a dietary replacement for
      whole cottonseed as determined by rumination and total chewing activity, milk fat
      percentage, and efficiency of 4% fat-corrected milk (FCM) production. Twenty-six
      Holstein dairy cows (14 multiparous; 35 +/- 12 d of lactation) were assigned
      randomly to one of two total mixed rations (TMR) for 15 wk. The whole cottonseed
      TMR and the soybean plus soybean hull TMR contained 40% of a 45:55 mixture of
      alfalfa and corn silages (dry matter basis) and either 15% cottonseed or 15%
      soybeans, 8% soybean hulls, and 0.7% sodium bicarbonate. Both TMR provided 60% of
      dietary neutral detergent fiber from forage. The TMR, fed twice daily, were
      isonitrogenous (17.5% crude protein) and equal in neutral detergent fiber (30%).
      The TMR had no effect on dry matter intake (24.8 kg/d). The cottonseed TMR
      stimulated greater rumination and total chewing activity. Although milk
      production was greater for cows fed the cottonseed TMR (35.7 vs. 34.1 kg/d), milk
      fat production was unaffected by TMR (3.72%). The efficiency of 4% FCM production
      was similar for cows fed the cottonseed and soybean plus soybean hull TMR (1.33),
      and both TMR resulted in a positive net energy balance (10.9 Mcal/d). A
      combination of soybeans, soybean hulls, and sodium bicarbonate was an effective
      alternative to whole cottonseed as measured by the efficiency of FCM production.

PMID- 9241597
TI  - Effect of whole cottonseed, gossypol, and ruminally protected lysine
      supplementation on milk yield and composition.
AB  - To determine whether the gossypol content of the diet affected availability of
      dietary Lys, 4 cows with ruminal and duodenal cannulas and 16 intact cows in
      early lactation were assigned to diets containing either glanded cottonseed,
      glanded cottonseed plus 15 g/d of ruminally protected Lys, glandless cottonseed,
      or glandless cottonseed plus 15 g/d of ruminally protected Lys. The experimental
      design was a 4 x 4 Latin square design with 3-wk experimental periods. Gossypol
      concentrations in plasma were lower when cows were fed glandless cottonseed.
      Lysine supplementation increased the flow and percentage of Lys in duodenal
      digesta and increased the concentration of Lys in plasma. Neither type of
      cottonseed nor Lys supplementation affected dry matter intake. Yields of milk and
      fat-corrected milk from cannulated cows were not affected by diet, but yields
      from intact cows were increased by Lys supplementation. For both cannulated and
      intact cows, Lys supplementation increased the percentage of milk protein, and
      milk protein yield was increased by Lys in intact cows. Dietary gossypol did not
      affect the response to Lys, indicating that dietary gossypol had little or no
      effect on the availability of Lys for dairy cows.

PMID- 9241598
TI  - Influence of time of feeding a protein meal on ruminal fermentation and
      forestomach digestion in dairy cows.
AB  - Four ruminally and duodenally cannulated dairy cows in midlactation were fed
      twice daily a mixed diet of alfalfa silage and whole-crop oat silage and a
      concentrate consisting of primarily barley grain. A high protein supplement was
      fed at approximately 15% of the estimated dry matter intake of the mixed diet
      once daily at 0830 h, 0.5 h after the morning meal (day), or at 0030 h, 7.5 h
      after the evening meal (night). Cows fed the protein supplement during the night
      had higher apparent forestomach digestion of organic matter and crude protein.
      Ruminal concentrations of all volatile fatty acids, except isobutyrate, were
      higher for cows fed the protein supplement during the night. Although ruminal pH
      and concentrations of ammonia N did not differ between treatments, time by
      treatment interactions indicated that the feeding times of the protein supplement
      influenced diurnal patterns of ruminal fermentation. The flow of nonbacterial
      nonammonia N at the duodenum, as a proportion of N intake, was lower for cows fed
      the protein supplement during the night, but production of milk fat was higher.
      Results were consistent with a mechanism whereby protein fed during the night
      stimulated ruminal fermentation, particularly during the night, resulting in
      greater forestomach digestion of organic matter and less escape of dietary
      protein from the forestomach. Clearly, the different feeding times of this
      protein supplement changed the nutritional value of the overall diet.

PMID- 9241599
TI  - Production and composition of milk from Jersey cows administered bovine
      somatotropin and fed ruminally protected amino acids.
AB  - Eight multiparous and 4 primiparous Jersey cows averaging 92 d of lactation were
      utilized in a replicated 4 x 4 Latin square design with 28-d periods to determine
      responses to bovine somatotropin (bST) and ruminally protected Met and Lys when
      diets were fed that contained supplemental fat. Treatments were 1) control [no
      bST or ruminally protected amino acids (AA)], 2) control plus bST, 3) control
      plus ruminally protected AA, and 4) control plus bST plus ruminally protected AA.
      Dry matter intake was increased by bST but was unaffected by ruminally protected
      AA. Milk yield was increased by bST but was not altered by ruminally protected AA
      compared with the control diet. The bST tended to increase percentages of fat and
      total solids in milk and increased yields of fat, protein, 3.5% fat-corrected
      milk, and total solids. Ruminally protected AA increased percentages of fat,
      protein, and total solids in milk; however, yields of milk components were
      unaffected by ruminally protected AA. Body weight and body condition scores were
      unaffected by treatment. Concentrations of essential AA in plasma were unaffected
      by bST administration. Ruminally protected Met and Lys increased the
      concentration of Met and tended to increase the concentration of Lys in plasma.
      The lack of an increase in yields of milk and milk protein when ruminally
      protected AA were fed suggests that adequate amounts of Met and Lys were supplied
      by the control diet and protein reserves of the cows to meet the AA requirements
      for synthesis of milk and milk components.

PMID- 9241600
TI  - Zinc oxide and amino acids as sources of dietary zinc for calves: effects on
      uptake and immunity.
AB  - Calf starter diets were formulated to contain 60 ppm of Zn, 150 or 300 ppm of Zn
      in the form of Zn-Met and Zn-Lys, or 300 ppm of Zn in the form of ZnO to compare
      relative bioavailability and effects on immunity. Holstein heifer calves were
      weaned at wk 5 and fed experimental starter diets from wk 6 to 12. Feed intake,
      body weight, Zn concentrations in liver and serum fractions, and mineral
      concentrations in serum were measured to determine the effects of treatment. In
      addition, peripheral blood lymphocyte blastogenesis, interleukin-2 production,
      cytotoxic activity, and the ability of blood neutrophils to phagocytose and kill
      bacteria were assessed at wk 0, 2, 4, and 6 of the trial. Feed intakes and body
      weight gains were similar among calves. Concentrations of Zn in serum were
      elevated in calves fed 300 ppm of Zn as Zn-Met and Zn-Lys but not in calves fed
      ZnO. Concentrations of Zn in liver were significantly elevated by 300 ppm of Zn
      in the form of Zn-Met and Zn-Lys (360 micrograms/g) but not by the other Zn
      treatments or by the control (245 micrograms/g). No treatment had an effect on
      the concentrations of Lys and Met in serum; however, concentrations of Lys did
      decrease in serum as the age of the calves increased. There was no significant
      treatment effect on mitogen-induced lymphocyte blastogenesis, interleukin-2
      production, lymphocyte cytotoxicity, or phagocytic and intracellular killing
      ability of blood neutrophils. These data indicated greater absorption and
      retention of Zn when administered in the form of Zn-Met and Zn-Lys than that when
      ZnO was administered to young calves. However, there was no advantage to the
      immune function of extra dietary Zn.

PMID- 9241601
TI  - Polymorphisms of bovine beta-lactoglobulin promoter and differences in the
      binding affinity of activator protein-2 transcription factor.
AB  - Differential production of the two most common allelic variants of beta
      lactoglobulin (LG), beta-LG A and beta-LG B, has been observed using PAGE. This
      study evaluated 733 bp of the beta-LG promoter region and 92 bp of the first exon
      for possible polymorphisms using denaturing gradient gel electrophoresis and
      nucleotide sequence analysis. Within this region, 13 single nucleotide
      substitution polymorphisms were detected. Twelve polymorphisms were allele
      specific, and one appeared to be polymorphic only for the B allele. Several
      potential binding sites for transcription factors were found within the promoter
      sequence. This study investigated the role of the G to C transversion within a
      consensus binding site for activator protein-2 at position-430 bp upstream from
      the transcription initiation site. Using the DNase-I footprint assay, we
      confirmed the functional importance of this point mutation and showed different
      binding affinities of activator protein-2 for both alleles. We discuss the
      possible regulatory role of activator protein-2 in the transcriptional regulation
      of the beta-LG gene and propose the activator protein-2 transcription factor as a
      modulator of gene expression of beta-LG.

PMID- 9241602
TI  - Prediction of transmitting abilities for productive life and lifetime
      profitability from production, somatic cell count, and type traits in milk
      markets for fluid milk and cheese.
AB  - Two net income functions were constructed to reflect differences in value of
      carrier, protein, and somatic cell score (SCS) between milk markets for fluid
      milk and those for cheese. Individual costs were for production of carrier
      (water, lactose, and minerals), fat, and protein. Totals for net income from a
      lactation were adjusted for the opportunity cost of postponed replacement using
      all herdmates on test. Heritabilities and correlations were estimated with a
      multiple-trait sire model using 52,688 registered and grade (24%) cows that were
      classified daughters of 844 bulls included in the Sire Evaluation for Type
      program of the Holstein Association of America. Although the genetic correlation
      between the net income traits was high (0.92), the resulting economic weights
      were quite different. Indexes to select for net income for a fluid milk market
      weighted milk production much more than it weighted fat or SCS and selected
      against protein yield. Indexes for a cheese market gave more weight to milk
      components, SCS, and traits related to productive life. The removal of some type
      traits had little effect on the evaluation of either net income trait. In
      contrast, weights for prediction of productive life from SCS and the production
      and type traits became more stable when strength, fore udder, and rear udder
      heights were removed. Removal of some of the type traits that were used for
      prediction reduced multicollinearity and the variance of weights without
      sacrificing accuracy.

PMID- 9241603
TI  - Technical and economic models to support heifer management decisions: basic
      concepts.
AB  - To maximize herd profits, dairy farmers are faced with the complex dilemma of
      minimizing costs that are associated with rearing heifers while ensuring or
      enhancing lifetime economic productivity. Decisions about heifer management
      interact with underlying biological aspects of growth, thereby influencing future
      profitability. A thorough understanding of these biological interactions is
      lacking. Studies based on models could be useful in the evaluation of various
      rearing strategies. Currently available models for dairy cattle primarily focus
      on the dairy cow. In a dairy farm production system, management decisions
      concerning the rearing of livestock and the replacement of dairy cows strongly
      influence each other. In a model that describes the dairy herd as a multiple
      component system, opportunity is greater to coordinate rearing and replacement
      policies. Expected benefits of such a model are discussed.

PMID- 9241604
TI  - Measuring the effectiveness of fiber by animal response trials.
AB  - Chemical analysis of neutral detergent fiber (NDF) provides a useful description
      of forages and other feeds. However, use of NDF as the sole measure of the fiber
      contribution of a feed has proved problematic for two classes of feeds: forages
      processed into differing physical forms and high fiber by-products. By-products
      and physically fine forages contribute to the fiber value of dairy rations, but
      contribute less than long forages do. Therefore, some discount factors must be
      assigned to these feeds if fiber requirements are to be used in balancing the
      carbohydrate portion of dairy diets. The effectiveness factors applied to NDF
      from these feeds provide an improved measure of fiber value. The assumptions and
      trial designs used to measure the effectiveness of NDF based on any single animal
      response variable are discussed, and improved approaches are suggested. The use
      of different response variables to measure physical and overall fiber
      effectiveness is discussed. Measured effectiveness of a high fiber feed differs
      when estimated by chewing, by the ratio of acetate to propionate, or by milk fat
      concentration. In all cases, inclusion of negative control treatments is
      necessary to measure the effect of removing fiber without introducing a
      substitute fiber source.

PMID- 9241605
TI  - Effects of feeding nonforage fiber sources on site of fiber digestion.
AB  - Although many nonforage fiber sources have high extents of neutral detergent
      fiber (NDF) digestion, most have rates of digestion similar to or slower than the
      rates of forage NDF digestion. Rates of NDF digestion vary considerably among and
      within sources of by-products. Digestion kinetics also vary because of the
      technique used (in vitro versus in situ) and because of high amounts of dietary
      concentrate. Based on available data for passage rate and specific gravity
      measurements, rates of passage of nonforage fiber sources from the rumen of high
      producing cows appear to be faster than those of forages. Therefore, the
      potential to shift NDF digestion to the hindgut has been discussed. To account
      for variability in ruminal and total tract digestibility of NDF, multiple
      regression analysis was used to indicate that nonforage NDF percentage in the
      diet had about two-thirds the positive response on total tract NDF digestion that
      forage NDF percentage did. Although the loss of potentially digestible NDF may
      occur, DMI does not appear to decrease much until forage NDF is below 14 to 16%
      of dietary DM. Conversely, replacement of starch with nonforage NDF appears to
      increase digestibility of fiber, mostly in diets with high concentrations of
      nonfiber carbohydrates, apparently because of reduced negative associative
      effects. Increasing the concentration of total NDF above 35% also can decrease
      DMI with little improvement in NDF digestibility. Increased knowledge of the
      kinetics of digestion and the passage of various nonforage fiber sources used to
      replace forage or concentrate should increase the accuracy and precision of
      dynamic models, thereby increasing the flexibility and utility of nonforage fiber
      sources in dairy rations.

PMID- 9241606
TI  - Interactions among forages and nonforage fiber sources.
AB  - Source, amount, and physical characteristics of dietary forage can interact with
      nonforage fiber sources and influence ruminal and total tract fiber digestion,
      passage, and performance of dairy cows fed diets containing substantial nonforage
      fiber in place of forage. Dietary NDF from forage can be reduced to < = 60% and
      still provide sufficient amounts of effective fiber for FCM production that is
      similar to or superior to that with high forage diets. Because of small particle
      size and high specific gravity, increased ruminal rate of passage may be
      responsible for lower ruminal NDF digestibility of nonforage fiber sources fed at
      high dietary amounts. As the amount of soybean hulls increased from 50 to 95% of
      a pelleted mix for dairy cows, passage rate increased by 8%. In five studies, the
      digestion of soybean hull diets was improved by the addition of coarse forage.
      Fiber digestibility might have improved because coarse hay increased ruminal
      retention time of nonforage fiber sources and allowed more complete digestion.
      Addition of coarsely chopped alfalfa hay to diets based on silage containing 25%
      soybean hulls increased ruminal mat consistency by 49% and tended to slow the
      ruminal escape rate of soybean hulls by 16%. When high percentage of nonforage
      fiber are fed, the amount of dietary forage is necessarily low, and forage
      particle size should be adequate to stimulate rumination and entrap small feed
      particles. The amount and particle size of forage in the diet interacts with the
      substituted nonforage fiber source to determine the net impact on the rate of
      ruminal digestion and passage of nonforage fiber.

PMID- 9241607
TI  - Relationship between fermentation acid production in the rumen and the
      requirement for physically effective fiber.
AB  - The content of ruminally fermented OM in the diet affects the fiber requirement
      of dairy cattle. Physically effective fiber is the fraction of feed that
      stimulates chewing activity. Chewing, in turn, stimulates saliva secretion.
      Bicarbonate and phosphate buffers in saliva neutralize acids produced by
      fermentation of OM in the rumen. The balance between the production of
      fermentation acid and buffer secretion is a major determinant of ruminal pH. Low
      ruminal pH may decrease DMI, fiber digestibility, and microbial yield and thus
      decrease milk production and increase feed costs. Diets should be formulated to
      maintain adequate mean ruminal pH, and variation in ruminal pH should be
      minimized by feeding management. The fraction of OM that is fermented in the
      rumen varies greatly among diets. This variation affects the amount of
      fermentation acids produced and directly affects the amount of physically
      effective fiber that is required to maintain adequate ruminal pH. Acid production
      in the rumen is due primarily to fermentation of carbohydrates, which represent
      over 65% of the DM in diets of dairy cows and have the most variable ruminal
      degradation across diets. The non-fiber carbohydrate content of the diet is often
      used as a proxy for ruminal fermentability, but this measure is inadequate.
      Ruminal fermentation of both nonfiber carbohydrate and fiber is extremely
      variable, and this variability is not related to the nonfiber carbohydrate
      content of the diet. The interaction of ruminally fermented carbohydrate and
      physically effective fiber must be considered when diets for dairy cattle are
      evaluated and formulated.

PMID- 9241608
TI  - Creating a system for meeting the fiber requirements of dairy cows.
AB  - Current NRC recommendations for dairy cattle provide limited guidance to
      nutritionists for meeting the fiber and carbohydrate needs of lactating cows. The
      NRC provide only minimum recommendations for fiber and no accommodation for
      factors such as physical effectiveness of fiber, interactions with nonfibrous
      carbohydrates, or animal attributes, which can affect the optimality of dairy
      rations. To be an improvement, any new system for meeting the fiber requirements
      of dairy cows must be based on 1) feed characteristics that can be defined and
      preferably be determined quantitatively using routine laboratory methods and 2)
      animal requirements that correspond to critical feed characteristics and vary
      with feeding situation, ration composition, and attributes of the animal.
      Published data were used to develop coefficients for defining the physical
      effectiveness or roughage value of feeds and the fiber requirements of dairy
      cows. Information in this paper is intended to provide practical guidelines for
      improving current fiber recommendations and to serve as an idealized framework
      for future research on meeting the fiber requirements of dairy cows. The system
      is based on NDF as the measure of total chemical fiber in feeds. Adjustments for
      the effectiveness of NDF in maintaining milk fat production and optimizing
      ruminal fermentation are based on the particle size and inherent characteristics
      of NDF that affect chewing activity, ruminal pH, and milk fat production.

PMID- 9241609
TI  - Assays for antibodies to human interferon-alpha: the need for standardization.
AB  - Since the first reported occurrence of anti-interferon (IFN) antibodies in 1981,
      the reported incidence of antibody production has differed enormously. In some
      clinical trials of human IFN preparations, no patients developed antibodies,
      whereas other studies reported an incidence of more than 80%. In patients with
      hepatitis C, the reported incidence varies from 7% to 61%. One of the factors
      contributing to the variability of the results is the lack of a standard assay
      system to measure antibodies to IFNs. In 1994, a Concerted Action funded by the
      European Commission started to coordinate studies into the immunogenicity of
      recombinant DNA-derived pharmaceuticals. These studies aimed to examine whether
      antibodies could interfere with the efficacy of treatment and also studied the
      long-term effects on cytokines produced by the patients themselves. Only when a
      well-calibrated and standardized assay is available, however, will it be possible
      to define the biologically relevant titer of antibody. Assays for both binding
      and neutralizing antibodies are discussed here.

PMID- 9241610
TI  - Interferon standardization and designations.
AB  - A large number of different human and nonhuman interferon (IFN) preparations are
      now available for either research purposes or commercial use. Consistency of
      results can be achieved only through rigorous application of biologic standards
      and individual species designation. International standards for the potency
      determinations of these preparations have been produced in accordance with World
      Health Organization (WHO) guidelines and are available for calibrating assays.
      Until recently, potency has been assessed purely as a measure of antiviral
      activity expressed in international units. Other biologic properties are now also
      being considered, including antiproliferation and immunomodulation. Indirect
      methods of measuring IFN, such as radioimmunoassay or enzyme immunoassay, if
      fully validated, may also provide useful estimates of function. Reference
      antisera are useful for characterizing IFN preparations and for monitoring
      neutralization assays for detecting anti-IFN antibodies but should not have a
      function in assay calibration. Factors to be considered when referring to
      specific designations for pure IFN species include distinctions for the species
      of origin, any mutant or hybrid forms, the method of production, and the presence
      of additional glycosylation.

PMID- 9241611
TI  - Interferon immunogenicity: technical evaluation of interferon-alpha 2a.
AB  - Observations from some studies with interferon-alpha 2a (IFN-alpha 2a) have shown
      the presence of neutralizing antibodies in a proportion of patients. As a result,
      an investigation into the production of antibodies to IFN-alpha 2a was
      undertaken. A number of technical aspects of its production and storage were
      investigated, including the possibility of an incorrect structure, which could
      affect the immunogenicity of the IFN-alpha 2a molecule. These investigations
      demonstrated the presence, in vials of IFN-alpha 2a, of both interferon
      interferon (IFN-IFN) aggregates and aggregates of interferon with human serum
      albumin (HSA), the excipient of the galenical form of IFN-alpha 2a (IFN-HSA)
      aggregates. The amount of aggregates is temperature dependent, there being very
      little increase in aggregate content over time when vials are stored at 4 degrees
      C. The relative immunogenicity of IFN-alpha 2a increased when the vials were
      stored at ambient temperature but not when stored at 4 degrees C. These findings
      demonstrate that the immunogenicity of IFN-alpha 2a is likely to be related to
      the storage temperature. Storage of IFN-alpha 2a vials at 2-8 degrees C is now
      recommended. A new formulation has been introduced that does not contain HSA as
      an excipient, removing the possibility of IFN-HSA aggregation.

PMID- 9241612
TI  - Interferon immunogenicity: preclinical evaluation of interferon-alpha 2a.
AB  - A preclinical evaluation of the immunogenicity of various preparations of
      interferon-alpha (IFN-alpha) was performed with in vitro and in vivo animal
      models. The distribution of genes for IFN-alpha 2a, IFN-alpha 2b, and IFN-alpha
      2c in various cell populations and the response of human T cell clones to IFN
      alpha peptides were investigated. The immunogenicity of IFN-alpha in IFN-alpha 2b
      transgenic mice and factors that influence the immunogenicity of IFN-alpha in
      normal mice were also studied. The genes for IFN-alpha 2a and IFN-alpha 2b were
      found in KG-1 cells, whereas IFN-alpha 2b and IFN-alpha 2c genes were present in
      Namalwa cells. No difference in proliferation of human T cells, T cell lines, or
      T cell clones could be obtained with IFN-alpha peptides. In transgenic mice
      bearing the human IFN-alpha 2b gene, no antibody response was obtained following
      immunization with either IFN-alpha 2a or IFN-alpha 2b. Normal mice immunized with
      either IFN-alpha 2a or IFN-alpha 2b produced equivalent titers of antibodies,
      which cross-reacted with both IFNs. Studies evaluating the relative
      immunogenicity of IFN-alpha in normal mice demonstrated that a number of
      treatment and host variables can modulate immunogenicity of IFN-alpha
      preparations.

PMID- 9241613
TI  - Clinical investigation of the immunogenicity of interferon-alpha 2a.
AB  - The following confounding array of variables can affect the reporting of
      antibodies to interferon (IFN)-alpha or any other protein injected into humans
      for prophylactic or therapeutic purposes: route, dose, frequency, and duration of
      administration; timing and frequency of blood sampling; methods used to determine
      antibody presence (sensitivity); calculation of the units used to report the
      results; intrinsic immunogenicity of the protein product; major
      histocompatibility complex genotype of the challenged individual; associated
      diseases and medication. Without specification of all these factors, it is
      difficult to put forward a valid statement from the published literature
      regarding the comparative incidence of antibodies to various forms of IFN.
      Furthermore, because units are not standardized and rarely reported, it becomes
      impossible to make any comparisons of antibody titers. This evaluation confirms,
      by clinical trial results, the decrease in immunogenicity observed in vitro and
      in vivo of different IFN-alpha 2a products manufactured between 1989 and 1993
      following incremental improvements in process specifications and expanded quality
      control. Serial serum samples were taken, prepared, stored, and shipped according
      to identical protocols in five different clinical trials performed with IFN-alpha
      2a between 1989 and 1995 in comparable patient populations with chronic hepatitis
      C. The coded samples were screened using sensitive enzyme immunoassay (EIA).
      Positive samples were further analyzed and quantified by bioassay [antiviral
      inhibition assay (AVIA)]. The data from these clinical trials confirm the results
      from extensive preclinical testing. Refrigerated lyophilisate and a new human
      serum albumin (HSA)-free formulation of IFN-alpha 2a, produced according to the
      latest process specification, are less immunogenic than earlier products.

PMID- 9241614
TI  - Clinical relevance of anti-interferon antibodies in the serum of chronic
      hepatitis C patients treated with interferon-alpha.
AB  - The development of anti-interferon (anti-IFN) antibodies in the serum of patients
      undergoing antiviral therapy has been postulated as one possible cause of
      interpatient variability in response to therapy. We analyzed the relationship
      between the appearance of anti-IFN antibodies and the loss of response to
      interferon-alpha (IFN-alpha), as characterized by a breakthrough of serum
      aminotransferase after a period of complete biochemical remission. The analysis
      involved clinical trials where neutralizing anti-IFN antibodies were detected by
      standardized and comparable methods. The results show that a time relationship
      between breakthrough and anti-IFN antibodies is observed in only a few cases and
      is independent of the type of IFN-alpha preparation used. Thus, causes of IFN
      resistance other than anti-IFN antibodies must also be implicated in most
      breakthrough cases. Another potential is the selection of drug-resistant viral
      strains. Current ration behavior following the appearance of breakthrough (from
      whatever cause) in clinical practice advocates changing treatment to a different
      type of IFN-alpha. The detection of anti-IFN enzyme-linked immunosorbent assay
      (ELISA) antibodies or IFN neutralizing antibodies does not appear to provide any
      additional information for decision making.

PMID- 9241616
TI  - Clinical experience of antibodies to interferon-alpha during treatment of chronic
      myeloid leukemia.
AB  - Interferon-alpha (IFN-alpha) remains the only viable alternative to bone marrow
      transplantation for patients with chronic myeloid leukemia (CML) and is the
      treatment of choice in many circumstances. IFN-alpha can induce hematologic
      remissions in most patients with CML and suppresses the Philadelphia chromosome
      positive cell clone in 30%-40% of hematologically responsive patients. IFN-alpha
      can also prolong the length of the chronic disease phase and survival time in
      patients who achieve a karyotypic response. A third of patients, however, never
      respond to IFN-alpha, and a proportion of the initial responders will later
      become resistant. It has been suggested that the induction of anti-IFN-alpha
      antibodies might be one of the reasons for resistance to IFN-alpha. It is
      difficult to evaluate the factors that influence antibody induction and the
      effects of these antibodies on clinical results. The source of IFN-alpha product,
      trial design, and differences in the sensitivity of the assays used to measure
      antibodies are all factors that need to be considered.

PMID- 9241615
TI  - In vivo development of antibody to interferons: an update to 1996.
AB  - It has been well established that a percentage of patients receiving interferon
      (IFN) produce antibodies that can neutralize its action or bind to the molecule.
      There are also indications that the development of neutralizing antibodies to IFN
      may be associated with failure of IFN therapy. This article reviews such
      observations and addresses some of the continuing questions on this issue.

PMID- 9241617
TI  - Natural autoantibodies to interferons.
AB  - Natural antibodies that appear to have arisen in the absence of direct antigenic
      stimulation often are present in the circulation. In healthy individuals, they
      are of low prevalence and generally show low affinity to their respective
      antigens, whereas in autoimmune disease, their frequency and affinity toward
      specific antigens are in many cases increased. In some autoimmune disease, the
      spontaneous occurrence of autoantibodies to antigens that are apparently
      unrelated to symptoms or pathology has been observed. For example, antibodies to
      interferon-alpha (IFN-alpha) have been observed in patients with systemic lupus
      erythematosus but appear to be of no clinical significance. Natural
      autoantibodies to IFN-alpha have also been found in other patients, including
      those with insulin-dependent diabetes mellitus, heart disease, or cancer and
      patients who have just received allogeneic bone marrow transplantation. A major
      property of IFN-alpha autoantibodies is their capacity to both bind to and
      neutralize the biologic activity of a range of IFN-alpha subtypes and natural IFN
      alpha preparations. Their origins and significance remain a matter for debate.

PMID- 9241618
TI  - What do the overall results of clinical trials and meta-analyses tell us about
      the efficacy of treatments?

PMID- 9241619
TI  - Still a role for plasma exchange in rapidly progressive glomerulonephritis?
AB  - Plasmapheresis combined with immunosuppression dramatically improved the survival
      of patients with Goodpasture's disease in the late 1970's. The presence of
      circulating pathogenic autoantibodies in this disease provided a logical
      rationale for the use of plasma exchange therapy. Careful analysis of the
      response to treatment has suggested that patients presenting with a serum
      creatinine < 600 mumol/I have the most benefit from plasma exchange. Subsequently
      plasmapheresis has been tried in a variety of other nephritides, predominantly
      those causing rapidly progressive glomerulonephritis, with variable success.
      Initial studies failed adequately to distinguish patients with a number of quite
      distinct causes of crescentic nephritis. However it has become clear that plasma
      exchange significantly improves the outcome of patients with pauci-immune
      crescentic glomerulonephritis who present with severe renal failure requiring
      dialysis, but not those with less severe renal disease.

PMID- 9241620
TI  - Treatment of idiopathic nephrotic syndrome with cyclosporine A.
AB  - Cyclosporine A has been empirically used for more than 12 years in the treatment
      of idiopathic nephrotic syndrome, in both children and adults. There is
      consistent evidence, from both experimental and human studies, that the highly
      lipophilic cyclosporine molecule diminishes or abolishes proteinuria by two
      differing mechanisms. The first is its immunosuppressive action, which is
      presumably directed toward secretion of a glomerular permeability factor. The
      second appears to be a non-immunologic effect on glomerular permselectivity,
      explaining reduced proteinuria in various etiologies of nephrotic syndrome with
      no immunologic background. The success rate for inducing remission of idiopathic
      nephrotic syndrome is highest in steroid-dependent forms, essentially observed in
      minimal change disease where complete remission is achieved in 75% of cases. It
      is lowest in steroid-resistant idiopathic nephrotic syndrome, especially when
      accompanied with lesions of focal segmental glomerulosclerosis, with a success
      rate in the order of 20% complete remission and 25% partial remission. The
      initial dosage in adults should not exceed 5.5 mg/kg/day which was shown to be
      the cut-off level of toxicity in renal biopsy-based studies. It is slightly
      higher in children, and some studies suggest that high serum cholesterol levels
      should allow higher dosages for increased remission rates without additional
      toxicity. Long-term treatment of INS requires serial monitoring of renal function
      with drug dosage reduction when serum creatinine rises by 30% over baseline, and
      it is recommended to carry out renal biopsy after 1 to 2 years of treatment to
      verify the absence of interstitial fibrosis even though renal function tests are
      apparently stable. Renal insufficiency and/or severe hypertension complicate
      treatment in approximately 10% of cases, essentially in FSG, in which the
      development of the primary renal disease, which is not controlled by CsA, is
      additive to the nephrotoxic potential of the drug. Cyclosporine dependency is the
      rule during the first year of treatment. However, in a meaningful number of
      cases, tapering CsA dosage to a stop or to a low maintenance dosage is compatible
      with stable remission without risk of nephrotoxicity. Therefore, cyclosporine,
      the main advantage of which is its corticosteroid-sparing effect, appears to be a
      significant advance in the treatment of idiopathic nephrotic syndrome.

PMID- 9241621
TI  - Extra-adrenal pheochromocytoma.
AB  - Extra-adrenal pheochromocytomas, or gangliomas, develop in the paraganglion
      chromaffin cells of the sympathetic nervous system. They account for 10% of all
      pheochromocytomas in adults and 30-40% in children. These tumors are usually
      larger than their adrenal counterpart. The most common site of extra-adrenal
      phenochromocytomas is the para-adrenal area, but they also occur at the aortic
      bifurcation, chest, inferior mesenteric and iliac arteries, bladder, heart and
      brain. In this report, we describe a 13-year-old girl with a pheochromocytoma
      along the course of the left ureter, a finding which to our knowledge was
      previously described only once. Clinical presentation, diagnosis, and treatment
      are similar to adrenal tumors. Patients should be closely monitored with serum
      and urine catecholamine determination and MIBG scan to detect any recurrence or
      distant metastasis. Prognosis is usually good if the tumor is detected early to
      avoid major complications related to catecholamine excess.

PMID- 9241622
TI  - Arteritis temporalis in a patient with microscopic polyangiitis.

PMID- 9241623
TI  - Effects of simvastatin and enalapril on serum lipoprotein concentrations and left
      ventricular mass in patients on dialysis. The Perfect Study Collaborative Group.
AB  - A randomised trial of simvastatin and enalapril in patients with chronic renal
      failure on dialysis: effects on serum lipoprotein concentrations and left
      ventricular mass. Left ventricular hypertrophy and abnormalities of lipoprotein
      metabolism are both possible contributors to the high risk of cardiovascular
      death in patients with chronic renal failure on dialysis. We investigated the
      effects of simvastatin on lipid and lipoprotein concentrations and the effects of
      enalapril on left ventricular mass in 107 patients receiving haemodialysis or
      continuous ambulatory peritoneal dialysis. Patients were randomised in a
      factorial design to receive simvastatin (10 mg daily) or placebo and enalapril
      (2.5-5 mg daily) or placebo. During follow-up, there was a significant excess of
      patients withdrawn from enalapril because of hypotension (2p = 0.002), and after
      6 months only 55% of those assigned enalapril were still on treatment. From
      baseline to 6 months, there were no statistically significant differences in left
      ventricular mass or left ventricular dimensions between patients assigned
      enalapril and those assigned placebo. Among the patients assigned simvastatin,
      total cholesterol was reduced by 13% (2p = 0.001), LDL cholesterol was reduced by
      17% (2p = 0.003) and apolipoprotein B was reduced by 12% (2p = 0.005) compared to
      patients assigned placebo. There were borderline significant (2p = 0.05 to 0.08)
      reductions in VLDL cholesterol, total triglyceride and VLDL triglycerides of 26%,
      12% and 17% respectively. Large-scale trials are now required to determine
      whether reductions in lipid and lipoprotein concentrations confer a reduction in
      coronary heart disease morbidity and mortality in patients on dialysis.

PMID- 9241624
TI  - Lp(a) levels: effects of progressive chronic renal failure and dietary
      manipulation.
AB  - Patients with chronic renal failure (CRF) have an increased risk of
      cardiovascular disease (CVD). Elevated lipoprotein(a) (LP(a)) levels have been
      shown to be an important risk factor for CVD. This study examined Lp(a) changes
      during the progression of renal disease in patients following different dietary
      regimens. Fifty-seven patients with CRF of different etiology and degree (mean
      age 58 +/- 10 yrs) were divided into four groups according to their serum
      creatinine (sCr) levels. The first group had sCr 1.5-3; the second 3-6; the third
      > 6, all on a conventional low-protein diet (CLPD), and the fourth had sCr > 6 on
      a supplemented vegetarian diet (SVD). Lp(a), apoproteins AI, B, E, CII, CIII,
      CII/CIII, Apo A/Apo B ratios and the lipid pattern (total cholesterol (TC) and
      its fractions LDL, HDL, HDL3 and triglycerides) were investigated. Patients with
      diabetes, proteinuria > 1.5 g/24 h, hepatic disease or taking contraceptives or
      lipid lowering drugs were excluded. Results were compared with a reference group
      (N = 12) with sCcr < 1. Lp(a) concentrations increased with the progression of
      renal failure, and a significant correlation was observed with sCr. Despite the
      elevated sCr levels, patients on the SVD had an almost normal Lp(a)
      concentration. Only 15% of the reference group had Lp(a) levels > 30 mg/dl,
      compared to 33%, 50% and 78% of the 1st, 2nd and 3rd groups and 38% of the 4th
      group. No relationship was found between Lp(a), lipids or apoproteins. Our
      results indicate that renal function influences Lp(a) levels and suggest a SVD
      helps to lower them. This might be ascribed to some antioxidant factors in the
      SVD.

PMID- 9241625
TI  - The role of Helicobacter species in newly recognized gastrointestinal tract
      diseases of animals.
AB  - Because Helicobacter pylori is now known to be a significant human pathogen,
      experimental animal models are increasingly being used to study the pathogenesis
      of this organism. Unfortunately, early studies failed to establish H. pylori in
      animal models, and surprisingly, Koch's postulates were initially fulfilled in
      two human volunteers. Germfree experiments performed in pigs and pups however
      established that H. pylori would colonize in these animals, and gastritis was
      induced. Certain macaque species and cats are now known to be naturally infected
      with H. pylori, and these animals are susceptible to experimentally induced
      infection with the organism as well. Interestingly, as the ability to manipulate
      and grow H. pylori in vitro increased, so did the ability to colonize it in
      animal models. Helicobacter pylori has now experimentally induced gastritis in
      germfree euthymic and nude mice and in conventionally housed mice. Six additional
      Helicobacter species have been isolated and identified from the stomachs of
      various mammals, including dogs, cats, ferrets, pigs, monkeys, and cheetahs;
      these organisms, similar to H. pylori, are associated with variable degrees of
      gastritis in their hosts. In addition to the discovery of gastric helicobacters,
      an increasing number of Helicobacter spp. have been isolated from the distal part
      of the gastrointestinal tracts of mammals and birds. Importantly, in one inbred
      strain of mice, A/JCr, persistent infection with H. hepaticus is linked to
      development of hepatic adenomas and adenocarcinomas. To date, the genus
      Helicobacter includes 17 named species as well as other formally unnamed closely
      related organisms. An overview of gastric helicobacters and naturally acquired
      Helicobacter spp.-induced disease in laboratory animals and, where appropriate,
      use of animal models to study H. pylori-associated gastric disease is presented.
      Similarities between Helicobacter infections and the epidemiology of the diseases
      induced by these bacteria in humans and animals also are highlighted.

PMID- 9241626
TI  - Prevalence of Herpesvirus papio 2 in baboons and identification of immunogenic
      viral polypeptides.
AB  - The prevalence of Herpesvirus papio 2 (HVP2) in several groups of captive and
      wild-caught baboons was determined by detection of anti-HVP2 antibodies in 133
      sera of adult baboons. Over 90% of newly imported (wild-caught) adult olive
      baboons (Papio anubis) from Kenya and chacma baboons (P. ursinus) from South
      Africa were found to have anti-HVP2 titers. Similarly, approximately 85% of
      captive breeding colony baboons (P. anubis and P. cynocephalus) were seropositive
      for HVP2. Infected animals were generally easily identifiable by enzyme-linked
      immunosorbent assay because anti-HVP2 IgG titers in immune animals were usually
      high (16,000 to 64,000). There was little variation in the relative reactivity
      patterns of individual HVP2-immune sera when tested against herpes simplex
      viruses 1 and 2, monkey B virus, H. cercopithecus 2, and HVP2, or against
      different HVP2 strains. Also, differences were not detected between reactivity of
      olive and chacma baboon immune sera. Analysis of the polypeptide specificity of
      immune sera by western blot identified four viral antigens that were consistent
      targets of immune sera. These antigens were the gB glycoprotein, a pair of
      unidentified glycoproteins of 80 to 100 kDa, the gD glycoprotein, and a series of
      smaller capsid proteins. Additional viral proteins were variably recognized by
      individual immune sera. The results of this study indicate that HVP2 is a common
      infection of baboons; there is little antigenic variation among HVP2 strains; and
      there are several HVP2 antigens that represent consistent targets of the anti
      HVP2 immune response of baboons.

PMID- 9241627
TI  - Screening for simian type-D retrovirus infection in macaques, using nested
      polymerase chain reaction.
AB  - A nested polymerase chain reaction (PCR) assay was developed to detect proviral
      DNA in peripheral blood mononuclear cells (PBMC) of macaques infected with simian
      type-D retrovirus (SRV/D). Primers were designed to amplify gag gene sequences of
      SRV/D serotype 1, 2, and 3 viral genomes and were used in a single assay for
      simultaneous detection of infection with SRV/D-1, SRV/D-2, or SRV/D-3. Results of
      plasmid dilution studies indicate sensitivity of nested PCR in the range of 1 to
      10 genomic copies. The PBMC samples from 395 macaques of unknown SRV/D status,
      obtained from several primate facilities, were tested in parallel by Western blot
      (immunoblot) analysis, virus isolation, and nested PCR. Infection was detected in
      60 (15.2%) animals by nested PCR, in 40 (10.1%) animals by virus isolation, and
      in 28 (7.1%) animals by immunoblot. All 40 culture-positive samples were positive
      by nested PCR. In addition, 11 of 23 immunoblot-positive/virus isolation-negative
      samples, 2 of 20 immunoblot-indeterminate/virus isolation-negative samples, and 7
      of 312 immunoblot-negative/virus isolation-negative samples were identified as
      positive by nested PCR. Nested PCR is a sensitive and specific assay for
      simultaneous screening for infection with serotypes 1, 2, and 3 of simian type D
      retrovirus, and is a powerful tool for rapid screening and surveillance in
      macaque colonies.

PMID- 9241628
TI  - Pulmonary histiocytosis in tree shrews (Tupaia belangeri).
AB  - Granulomatous lesions similar to those of pulmonary histiocytosis in rats
      developed spontaneously in the lungs of captive tree shrews. Incidence peaked in
      3-year-old tree shrews. Sex dependency was not observed, and development of the
      granulomas was unrelated to experimental procedures because the lesions were
      observed in animals from the breeding stock as well. The granulomas consisted of
      amorphous material, foam cells, and a few foreign body-type multinuclear giant
      cells; they also contained acicular clefts, often with some fibrous material.
      Alveolar septa within and adjacent to the granulomas were thickened in most
      instances, but did not contain inflammatory cells in appreciable numbers or
      amyloid. Only traces of cholesterol and calcium were detected in the amorphous
      material; neutral fat was stored in the foam cells and the amorphous masses.
      Fibers without birefringency were documented by polarization and scanning
      electron microscopy in the vicinity of granulomas, which in energy-dispersive X
      ray microanalysis consisted mostly of calcium, but lacked silicon.

PMID- 9241629
TI  - Lipid storage disease.

PMID- 9241630
TI  - Ultrasonographic pregnancy detection and inhalation anesthesia in the gray short
      tailed opossum (Monodelphis domestica).
AB  - Female gray short-tailed opossums (Monodelphis domestica) with known breeding
      dates were anesthetized with isoflurane for ultrasonographic pregnancy detection.
      Beginning on gestational day 9, gravid females could be identified using a 9-MHz
      mechanical sector-scanning transducer equipped with a standoff pad. Fluid-filled
      vesicles 3 to 4 mm in diameter were seen within the thick-walled uteri on
      gestational days 9 and 10. Visualization revealed loss of individual vesicles,
      with replacement by thick, irregular uterine walls and some free luminal fluid by
      gestational days 12 and 13. On the basis of subsequent birth of pups, sonographic
      diagnosis of pregnancy was accurate in 27 of 28 oppossums examined.

PMID- 9241631
TI  - Fate of allogeneic skin transplantations in a marsupial (Monodelphis domestica).
AB  - Previously we reported that the South American gray short-tailed opossum,
      Monodelphis domestica, had an MHC class-I locus similar to that of eutherian
      species. In addition to the detection of lymphocyte antigens by cytotoxic
      antisera, we concluded that this marsupial rejected allogeneic skin grafts, as
      would be expected of animals with MHC class-I polymorphism. However, this
      conclusion was based on a limited number of skin transplants that were assayed
      for only a short period. Here we report the results of 22 reciprocal skin grafts
      made between individuals of known genetic relationships. On the basis of gross
      inspection of the grafts and histologic examination, we found that the average
      time of the onset of graft rejection was about 19 days and that the average time
      for complete graft rejection was about 31 days. In general, it took longer for
      the onset of graft rejection among pairs of genetically related animals than
      among less related animals. These results indicate unequivocally that this
      marsupial species has a high degree of class-I polymorphism and rejects
      allogeneic skin transplants in a manner similar to but more slowly than eutherian
      mammals.

PMID- 9241632
TI  - Characterization of hypertensive and hypotensive inbred strains of mice.
AB  - The hypertensive inbred mouse strain, BPH/2, has high blood pressure early in
      life, compared with its hypotensive BPL/1 and normotensive BPN/3 controls. At 21
      weeks of age, the hypertensive mouse has a systolic blood pressure 60 mm Hg
      higher than that of the hypotensive mouse. The difference in blood pressure
      between hypertensive and hypotensive mice is associated with strain differences
      in heart rate, heart weight, relative heart weight, left ventricular mass, kidney
      weight, and hematocrit. These strains have been inbred by brother x sister
      matings for nearly 50 generations in the BPH/2 and BPL/1 strains, and for nearly
      40 generations in the BPN/3 strain.

PMID- 9241633
TI  - Clinical and clinicopathological assessment of serial phlebotomy in the Sprague
      Dawley rat.
AB  - Two studies, designed to mimic a single-dose, cross-over pharmacokinetic
      protocol, were conducted to gain a better understanding of the rat's response to
      multiple, frequent blood sampling. Parameters evaluated included body weight,
      clinical signs of disease, hematologic and serum biochemical analytes, organ
      weights, and histopathologic features. Study groups consisted of either 6 or 8
      male, viral antibody-free, Sprague Dawley rats. These included controls and blood
      collection groups that represented withdrawal of 10, 15, 20, 30, and 40% of
      estimated total blood volume. Volume of blood collected per time point was based
      on the total volume to be withdrawn divided by the 13 samples that were collected
      over 24 h. This regimen was repeated 2 weeks later. Samples were taken for
      clinical pathologic evaluation on the days subsequent to blood collection for
      both studies as follows: 0, 1, 2, and 3 days; 7, 8, or 9 days; and either 13 or
      14 days. In Study 1, samples were also taken on either days 15 or 16, and on 17
      or 18 after the second blood collection. Approximately 2 weeks after the second
      blood collection regimen, animals were euthanized. Animals in one study were
      necropsied, and selected tissues were taken for histologic examination. Analysis
      of variance, based on changes from baseline, was used to assess group
      differences. Results indicate that the rate of body-weight gain for the bled
      groups was not significantly different from that of the controls. Group
      differences in multiple hematologic parameters were significant. Changes were
      typical of acute blood-loss anemia, with positive or negative trends relating to
      the volume of blood removed. In addition, these changes were characterized by
      recovery to control values within approximately 14 days. Few statistically
      significant group differences were detected in serum biochemical values, and
      those detected were not biologically relevant. Although organ weights of bled
      groups were similar to those of controls, minimal to mild splenic hematopoiesis
      was present in all bled groups, compared with controls. These data indicate that
      removal of up to 40% of a rat's total blood volume over a 24-h period, and
      repeated 2 weeks later, caused no gross ill effects.

PMID- 9241634
TI  - Pica behavior associated with buprenorphine administration in the rat.
AB  - Marked gastric distention was-observed in rats 20 h after they underwent partial
      hepatectomy under isoflurane anesthesia and received buprenorphine (0.3 mg/kg of
      body weight) after surgery. Hardwood bedding comprised the bulk of the gastric
      contents. A study was undertaken to determine the cause of the pica behavior
      (consumption of non-nutritive substances) and resultant gastric distention. Ten
      week-old male Sprague Dawley rats were randomly assigned to one of six groups.
      Group-1 rats (n = 11) underwent laparotomy under isoflurane anesthesia, with
      buprenorphine (0.3 mg/kg) administered after surgery. Group-2 rats (n = 12)
      underwent laparotomy under isoflurane anesthesia with buprenorphine (0.05 mg/kg)
      administered after surgery. Group-3 rats (n = 24) underwent laparotomy under
      isoflurane anesthesia, with saline administered after surgery. Isoflurane was
      administered at the same rate, concentration, and duration for all groups that
      underwent laparotomy (groups 1 to 3). Buprenorphine or saline was administered
      subcutaneously as a single injection when anesthesia was discontinued (groups 1
      to 3). Group-4 rats (n = 6) received buprenorphine (0.3 mg/kg) only. Group-5 rats
      (n = 6) received buprenorphine (0.05 mg/kg) only. Group-6 rats (n = 12) received
      saline only. Rats not undergoing laparotomy (groups 4 to 6) received
      buprenorphine or saline 18 to 20 h before euthanasia. Rats were housed
      individually in filter-topped polycarbonate cages containing hardwood bedding. A
      purified, pelleted diet and water were offered ad libitum. Food and water
      consumption were measured over the posttreatment period. Eighteen to 20 h after
      treatment, rats were euthanized, each stomach and its contents were weighed,
      contents were examined grossly, and wet and dry gastric content weights were
      recorded. All weights were significantly (P < 0.05) increased in rats receiving
      buprenorphine administered after surgery (groups 1 and 2), compared with rats of
      the control group (group 3). Weights of the stomach and contents, wet gastric
      contents, and dry gastric contents were significantly (P < 0.05) increased in
      rats receiving 0.3 mg of buprenorphine/kg only (group 4), compared with values
      for their controls (group 6). Hardwood bedding comprised the bulk of the gastric
      contents in all groups receiving buprenorphine. Stomachs of rats not receiving
      buprenorphine contained the purified diet with little or no hardwood bedding.
      These results indicate that a single injection of buprenorphine at a dosage of
      0.05 or 0.3 mg/kg resulted in rats ingesting hardwood bedding, leading to gastric
      distention. It was concluded that pica behavior associated with administration of
      buprenorphine should be considered when evaluating experimental data from rats
      housed on contact bedding.

PMID- 9241635
TI  - Magnetic resonance imaging of the central nervous system of the rhesus monkey.
AB  - The purpose of the study reported here was to document the ability of magnetic
      resonance imaging to depict the imaging characteristics of normal structures
      within the central nervous system of adult rhesus monkeys. The head and the
      cervical and thoracic parts of the spinal cord of two rhesus monkeys were imaged
      in a clinical 1.5-T whole-body imager. Specific images were selected, and some
      notable structures were identified. Results of this study document the usefulness
      of MRI as an expeditious, noninvasive research and diagnostic imaging technique
      and illustrates the normal magnetic resonance signal patterns of the brain and
      spinal cord in rhesus monkeys.

PMID- 9241636
TI  - Superovulation of New Zealand white rabbits by continuous infusion of follicle
      stimulating hormone, using a micro-osmotic pump.
AB  - A successful method for superovulation of rabbits, which is more time effective
      than current protocols, has been established and consistently yields large
      numbers of fertilized ova. Subcutaneous microosmotic pumps were used to
      administer follicle-stimulating hormone (FSH) over a 3-day period to mature
      ovarian follicles. The amount of FSH administered was based on baseline serum FSH
      concentration in unmated New Zealand White does; as determined by
      radioimmunoassay. Treatment with FSH was followed by intravenous administration
      of human chorionic gonadotropin (hCG) to enhance ovulation. Hormonally primed
      does were then mated to mature, fertile bucks. Ova were collected 18 to 20 h
      after mating. This procedure resulted in an average yield of 37 ova/doe, with a
      72.3% fertilization rate. These results were consistent with those published for
      superovulation using multiple subcutaneous injections of FSH. This method
      provided a consistent high yield of fertilized ova per doe and required only a
      simple surgical procedure.

PMID- 9241637
TI  - High performance seizure-monitoring system using a vibration sensor and videotape
      recording: behavioral analysis of genetically epileptic rats.
AB  - A new seizure-monitoring apparatus containing a piezoceramic vibration sensor
      combined with videotape recording was developed. Behavioral analysis of Ihara's
      genetically epileptic rat (IGER), which is a recently developed novel mutant with
      spontaneously limbic-like seizures, was performed using this new device. Twenty 8
      month-old male IGERs were monitored continuously for 72 h. Abnormal behaviors
      were detected by use of a vibration recorder, and epileptic seizures were
      confirmed by videotape recordings taken synchronously with vibration recording.
      Representative forms of seizures were generalized convulsions and circling
      seizures. Generalized convulsions were found in 13 rats, and circling seizures in
      7 of 20 animals. Two rats had generalized and circling seizures, and two rats did
      not have seizures. Although there was no apparent circadian rhythm to the
      generalized seizures, circling seizures occurred mostly between 1800 and 0800 h.
      A correlation between the sleep-wake cycle and the occurrence of circling
      seizures seems likely. Without exception, all the seizure actions were recorded
      by the vibration recorder and the videotape recorder. To eliminate the risk of a
      false-negative result, investigators scrutinized the information obtained from
      the vibration sensor and the videotape recorder. The newly developed seizure
      monitoring system was found to facilitate detailed analysis of epileptic seizures
      in rats.

PMID- 9241638
TI  - Diagnostic exercise: infertility in two chimeric mice.

PMID- 9241639
TI  - Mouse strain and age affect susceptibility to experimentally induced genital
      trichomoniasis.

PMID- 9241640
TI  - Effects of the use of filtered microisolator tops on cage microenvironment and
      growth rate of mice.

PMID- 9241641
TI  - Natural atypical language dominance and language shifts from the right to the
      left hemisphere in right hemisphere pathology.

PMID- 9241642
TI  - How many cycles does a PCR need? Determinations of cycle numbers depending on the
      number of targets and the reaction efficiency factor.

PMID- 9241643
TI  - Magnetic resonance angiography: today and tomorrow.
AB  - Magnetic resonance angiography (MRA) has enjoyed enthusiastic success at many
      research institutions where it is now routinely used in place of invasive x-ray
      angiography (XRA) for a variety of applications. While the physical principles of
      MRA are well understood, there is still plenty of opportunity for growth in the
      coming years. Recent improvements in instrumentation have permitted more rapid
      acquisition and manipulation of larger data sets. Instruments in the future are
      sure to continue this trend as computer hardware becomes more capable and less
      expensive. New clinical applications will also expand the utility of MRA beyond
      its current use. MRA is already being used in peripheral vessels and it appears
      to have great potential in the abdomen. Research into MRA methods for coronary
      vessel imaging is also beginning to show intriguing results. In addition,
      preliminary research results suggest that interventional MRA may one day become a
      reality.

PMID- 9241644
TI  - Principles and applications of spiral CT.
AB  - Spiral CT is a new volume acquisition mode in x-ray computed tomography (CT)
      which was introduced in 1989. Anatomical ranges are scanned in continuous fashion
      in typically 20-60s, images can be reconstructed in arbitrarily fine increments
      at any desired position within the scanned volume. We will illustrate the basic
      principles of scanning and image reconstruction in spiral CT and explain special
      features regarding image quality and patient dose. Particular attention is given
      to improved and new clinical applications, like lesion detection, 3D imaging and
      CT angiography. Spiral CT has already replaced conventional slice-by-slice CT
      scanning in many applications and will be the standard scan mode in future CT
      systems.

PMID- 9241645
TI  - Advances in interventional radiology in oncology.
AB  - Interventional radiology (IR) includes all procedures performed percutaneously
      under US, fluoroscopy, CT or DSA guidance by a radiologist to obtain diagnostic
      and therapeutic achievements. According to the pathology under examination, these
      procedures may be applied alone, as a definite therapeutic tool, or together with
      other traditional techniques permitting an easier and more successful
      application. In this report the authors discuss briefly the IR possibilities in
      many oncological branches.

PMID- 9241646
TI  - HRCT studies of lung anatomy.
AB  - An accurate definition of lung anatomy is the first, necessary step to obtain an
      accurate and early diagnosis of diffuse and focal lung disease with HRCT.
      Secondary lobules are visible with conventional CT and HRCT as polygonal portions
      of lung parenchyma, surrounded by thin and incomplete septa and centred by a
      dense dot; acini are sometimes visible as rounded structures with a central dot.
      Morphological definition of these structures in normal subjects will greatly help
      in characterizing early signs of parenchymal disease.

PMID- 9241647
TI  - CT-guided biopsy of lung lesions.
AB  - CT is the most accurate method for guiding fine needle biopsies in deep and/or
      small sized lung and mediastinic lesions. The authors have performed 2109 CT
      guided lung biopsies (FNAB). The results are given in terms of sensitivity,
      specificity and rate of complications. In ever examination, Westcott or Chiba
      needles (22 or 21 gauge) were used. From 2109 lung examinations performed, 1413
      (66.99%) were positive, 538 (25.5%) negative, 15 (0.7%) suspicious and 143
      (6.78%) inadequate for diagnosis, 267 patients underwent surgical or clinical
      follow-up and, in all cases, the cytological diagnosis was confirmed. Other
      considerations were made on lesion topography, histological type, dimensions,
      complication rate, sensitivity, specificity and diagnostic accuracy. CT, of
      course, is the best method for guiding fine needle biopsy of the lung for its
      high spatial resolution and excellent anatomical definition, so that samples with
      smaller than 2 cm lesions, even in continuity with large vessels or other
      critical organs, are performed. Nevertheless, the result quality depends on the
      ability of the operator.

PMID- 9241648
TI  - Current status of radioimmunodetection.
AB  - Radioimmunodetection is a nuclear medicine technique that depends on in vivo
      detection of localization of antibodies and antibody forms carrying radioactivity
      for the purpose of diagnosis in patients with cancer. Current methods take
      advantage of tracers suitable for high resolution gamma-camera imaging, such as
      99mTc and 111In, for common tumors, such as colon and lung cancers. In addition,
      tracers such as 125I have been used for the intraoperative detection of
      metastatic deposits. These methods detect from 75 to 90% of metastatic deposits
      with high specificity, and typically contribute important diagnostic information,
      even in 25-40% of patients with occult disease.

PMID- 9241649
TI  - Gallium-67-citrate imaging in nuclear oncology.
AB  - Gallium-67-citrate is one of the most useful radiopharmaceuticals to detect
      tumors, stage extent of the disease, monitor response to treatment and
      distinguish recurrent disease from post-treatment changes. Gallium is likewise
      very sensitive to detect and locate infections and inflammatory foci. This
      application is extremely important in the management of immunocompromised cancer
      patients. Image interpretation should be tempered with full knowledge of the
      patients clinical condition, anatomic alterations due to prior surgery and
      correct timing of image acquisition. Early imaging at 4-6 h is useful to detect
      gastrointestinal infections, whereas 24 h imaging is used to evaluate chest
      infections. Although gallium-67 is a non-specific agent, the identification of
      the etiology of the inflammation may be improved by adequate clinical and
      laboratory information as well as correlation with other imaging modalities such
      as sonography and computerized x-ray tomography (CT). High dose (10 mCi) gallium
      67 single photon emission computed tomography (SPECT) imaging with image co
      registration is important for accurate uptake localization.

PMID- 9241650
TI  - PET FDG studies in oncology.
AB  - Positron emission tomography (PET) studies of cancer with the glucose analog 2-[F
      18]fluoro-2-deoxy-D-glucose (FDG) have emerged as both a useful research and
      clinical method for detecting (diagnosing), staging, and monitoring treatment
      responses in a variety of neoplasms, including tumors of the brain, head and
      neck, lung, breast, gastrointestinal and genitourinary systems, lymphatic system,
      musculoskeletal system, and other organ systems. In addition to FDG, many other
      positron emitting radiopharmaceuticals are under investigation and development in
      oncology, but the largest set of clinically relevant results to date has been
      acquired with FDG. Because most aggressive neoplasms have high glycolytic rates,
      neoplasms throughout the body may potentially be visualized with PET, using both
      standard transaxial imaging methods and techniques such as whole body PET imaging
      for surveying the entire body.

PMID- 9241651
TI  - PET imaging of lung tumours and mediastinal lymphoma.
AB  - Positron emission tomography (PET) of the lung is evaluated regarding its
      clinical practicability for staging of bronchogenic carcinomas and lymphomas.
      Stringent quality control, optimized acquisition and reconstruction techniques
      are of crucial importance. An analysis of 50 PET studies for tumour (T) and
      lymphnode (N) staging in comparison to CT shows that PET has the highest
      diagnostic accuracy to classify lesions and is the most promising technique for
      non-invasive staging. PET cannot be the first imaging modality, but if
      unnecessary or invasive procedures can be avoided, the additional expense of a
      PET study seems justified.

PMID- 9241652
TI  - The application of receptor theory to receptor-binding and enzyme-binding
      oncologic radiopharmaceuticals.
AB  - The successful imaging of tumor biochemistry using a receptor binding radiotracer
      is related to the affinity constant and the receptor concentration. The target to
      nontarget ratio can be predicted by steady state equations using in vitro data,
      although this is a necessary but not sufficient upper limit. The prediction of
      the sensitivity of the radiopharmaceutical to changes in the tumor biochemistry
      is not possible with this evaluation.

PMID- 9241653
TI  - In vitro receptor imaging for characterization of human solid tumors.
AB  - Since many of the factors involved in tumor growth and progression act through a
      receptor-mediated mechanism, we applied in vitro receptor imaging techniques to
      study the intratumoral distribution and concentration of receptor-molecules
      having experimental biological relevance in such processes. Here we summarize the
      results of a study concerning the role of urokinase receptor (uPAR) in the
      acquisition of an invasive phenotype by tumor cells. Independently of the system
      studied, we demonstrated that in vitro receptor imaging techniques can be used to
      define the biological characteristics of human solid tumors and can contribute to
      clarify the complex network of ligand/receptor interactions leading to tumor
      spread.

PMID- 9241654
TI  - Clinical applications of fusion imaging in oncology.
AB  - Recent developments in tumor imaging, made possible by advances in
      instrumentation and radiopharmaceuticals, has led to an increasing need for
      accurate anatomic correlation of single photon emission computed tomography
      (SPECT) and positron emission tomography (PET) images. Fusion imaging permits the
      functional strengths of SPECT and PET to be combined with the anatomic resolution
      of computed tomography (CT) and magnetic resonance imaging (MRI). Clinical
      applications of fusion imaging include the evaluation of brain tumors, lymphoma,
      hepatic lesions and monoclonal antibody studies. The continued development of
      these techniques will eventually allow fusion imaging to become a routine part of
      nuclear medicine practice.

PMID- 9241655
TI  - Current status of radioimmunotherapy.
AB  - Radioimmunotherapy with radiolabeled monoclonal antibodies is increasingly
      effective for hematopoietic tumors, with a number of investigators reporting
      persistent major responses. Radioimmunotherapy for solid tumors has been more
      difficult and only an occasional major response has been reported and these have
      so far not been persistent. Toxicity is predominantly hematopoietic, with
      platelets being most sensitive to the effects of radiation. Even at ultra-high
      doses (up to 28 mCi/kg of 131I), second organ toxicity has not been reached.
      Rational approaches to dose planning are becoming possible with improvements in
      dosimetry, based on quantitative SPECT and PET imaging. Current therapeutic
      indices for tumor/marrow, the most radiosensitive organ, are in the range of 5-10
      to 1. This is probably still too low for curative treatment of solid tumors, and
      further refinements, perhaps based on novel antibody formulations, are needed.

PMID- 9241656
TI  - Examination of purported probes of human CYP2B6.
AB  - 7-Ethoxy-4-trifluoromethylcoumarin (7-EFC) was examined as a substrate for
      cytochrome P450 (P450) in microsomes from human livers and expressed in B
      lymphoblastoid cells. The O-deethylation of 7-EFC to 7-hydroxy-4
      trifluoromethylcoumarin (7-HFC) varied over a liver bank (n = 19) by a factor of
      13 (40-507 pmol min-1 mg-1 protein). When compared with the ability of the bank
      of human liver samples to metabolize form-selective substrates of the P450, 7-HFC
      formation correlated strongly with the formation of the S-mephenytoin metabolite,
      nirvanol (r2 = 0.86, p < 0.0001). alpha-Napthoflavone (ANF),
      diethyldithiocarbamate (DDC) and chloramphenicol (CAP) inhibited the O
      deethylation of 7-EFC by microsomes from human livers by greater than 60%.
      Orphenadrine (ORP), a reported specific CYP2B6 inhibitor, was a less potent
      inhibitor of 7-HFC formation by microsomes from human liver than DDC or ANF.
      Using microsomes from B-lymphoblastoid cells expressing specific P450s, CYP2B6
      and CYP1A2 were found to produce substantial levels of 7-HFC whereas CYP2E1 and
      CYP2C19 produced detectable amounts of this metabolite. ORP inhibited expressed
      CYP2E1 and CYP2B6 mediated 7-HFC formation to a greater extent than the
      inhibition observed for CYP1A2. Methoxychlor and S-mephenytoin inhibited
      expressed CYP2B6 but not CYP1A2 mediated 7-EFC O-deethylation. Livers (n = 5)
      with high relative rates of 7-HFC formation displayed biphasic enzyme kinetics
      with the low K(m) site (average K(m) = 3.3 microM) demonstrating allosteric
      activation. Five livers with low relative rates of 7-HFC formation also exhibited
      biphasic kinetics but lacked evidence of an allosteric mechanism being involved
      in the low K(m) component (average K(m) = 2.4 microM). Furthermore, expressed
      CYP2B6 and CYP2E1 converted 7-EFC to 7-HFC with allosteric activation indicated,
      while CYP1A2 mediated metabolism of 7-EFC to 7-HFC best fit the classic Michaelis
      Menten model. A commercially available antibody to rat CYP2B, suggested to be
      specific for CYP2B6, was found to cross react with all members to the CYP2 family
      examined including CYP2C19, which possessed a nearly identical electrophoretic
      mobility to that of CYP2B6 in the system examined. In total, the evidence
      presented indicates that multiple P450s are involved in the formation of 7-HFC
      from 7-EFC, therefore this does not appear to be a useful or a selective probe of
      CYP2B6 catalytic activity. Furthermore, the specificity of both antibody and
      chemical inhibitor (ORP) probes previously suggested to be specific for CYP2B6 is
      also questioned.

PMID- 9241657
TI  - Epitope mapping of human CYP1A2 in dihydralazine-induced autoimmune hepatitis.
AB  - Dihydralazine-induced hepatitis is characterized by the presence of anti-liver
      microsomal (anti-LM) autoantibodies in the sera of patients. Cytochrome P450 1A2
      (CYP1A2), involved in the metabolism of dihydralazine, was shown to be a target
      for autoantibodies. In order to investigate further the relationship between drug
      metabolism and the pathogenesis of this drug-induced autoimmune disease, and
      since the specificity of anti-LM autoantibodies towards CYP1A2 has been
      determined, the antigenic site was further localized. By constructing fragments
      derived from CYP1A2 cDNA and probing the corresponding proteins with several anti
      LM sera, we were able to define a region (amino acid 335-471) which was
      immunoreactive with 100% of sera. An internal deletion in this region led to the
      loss of recognition by anti-LM autoantibodies, confirming that the epitope was
      conformational. Epitope mapping studies had previously been performed for CYP2D6,
      CYP17, CYP21A2, and recently for CYP3A1 and CYP2C9. Those data were compared with
      results obtained in the present study for CYP1A2.

PMID- 9241658
TI  - Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians.
AB  - The polymorphic cytochrome P450 2D6 (CYP2D6) causing poor, extensive or
      ultrarapid metabolism of several clinically important drugs exhibits pronounced
      interethnic variation. Ultrarapid metabolism is caused by multiple copies of
      active CYP2D6 genes and recently 29% of an Ethiopian population has been shown to
      carry duplicated or multiduplicated CYP2D6 genes, whereas the corresponding
      frequency in other black, Oriental and European populations investigated is 1-2%.
      In order to characterize the distribution of alleles with multiple CYP2D6 copies
      in a neighbouring population and to characterize the CYP2D locus in general among
      Saudi Arabians, the CYP2D6 genotype of a Saudi Arabian population was examined
      using restriction fragment length polymorphism (RFLP) analysis and allele
      specific polymerase chain reaction (PCR) amplification. Of 101 Saudi Arabians
      studied, 21 subjects had an EcoRI fragment indicative of CYP2D6 gene duplication.
      In contrast, only two individuals were heterozygous for a deletion of the whole
      gene (CYP2D6*5). The allele frequency of CYP2D6*4, the most common defective
      allele among Caucasians, was only 3.5% in the Saudi population. Two other
      alleles, CYP2D6*10 and *17, common in certain populations and which cause
      diminished enzyme activity, were found only at low allele frequencies of 3.0%
      each. These findings are in agreement with earlier Saudi Arabian phenotyping
      studies which reported a low frequency (1-2%) of poor metabolizers for CYP2D6
      probe drugs. In conclusion, the Saudi Arabian population studied exhibited very
      few defective alleles and a large number of subjects carried duplicated CYP2D6
      genes, implying a high conservation on functional CYP2D6 genes possibly due to
      dietary reasons and reveal the Saudi Arabians as an unique population in
      comparison with others examined.

PMID- 9241659
TI  - Polymorphism of the cytochrome P450 CYP2D6 gene in a European population:
      characterization of 48 mutations and 53 alleles, their frequencies and evolution.
AB  - The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various
      drugs of wide therapeutic use and is a presumed susceptibility factor for certain
      environmentally-induced diseases. Our aim was to define the mutations and alleles
      of the CYP2D6 gene and to evaluate their frequencies in the European population.
      Using polymerase chain reaction-single strand conformation polymorphism analysis,
      672 unrelated subjects were screened for mutations in the 9 exons of the gene and
      their exon-intron boundaries. A total of 48 point mutations were identified, of
      which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented
      52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of
      the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the
      2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor
      metabolizer subgroup. Fifty-three different alleles were characterized from the
      mutation pattern and by allele-specific sequencing. They are derived from three
      major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the
      null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account
      for about 87% of all alleles, while the remaining alleles occur with a frequency
      of 0.1%-2.7%. These data provide a solid basis for future epidemiological,
      clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight
      that the described single strand conformation polymorphism method can be
      successfully used in designing such studies.

PMID- 9241660
TI  - The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450
      with NADPH:cytochrome P450 oxidoreductase.
AB  - We have examined the kinetics of substrate metabolism by cDNA-expressed human
      CYP2C9 and the R144C variant. Both enzymes exhibited similar apparent K(m) values
      for (S)-warfarin 7-hydroxylation, diclofenac 4'-hydroxylation and lauric acid 11
      hydroxylation. In contrast, the R144C variant (relative to CYP2C9) had slower
      rates of metabolism for all three substrates. The difference was most pronounced
      for (S)-warfarin. Surprisingly, the magnitude of the difference was found to be
      dependent on the cytochrome P450 to NADPH-cytochrome P450 reductase (OR) ratio in
      the system (the difference being more pronounced at higher OR to P450 ratios)
      implying that the R144C change affects interaction of the P450 with OR. The rates
      of (S)-warfarin 7-hydroxylation by CYP2C9 and the R144C variant also exhibited
      differential dependence on salt concentration which further supported a
      difference in interaction with OR. When OR was bypassed and the hydroxylation was
      supported by cumene hydroperoxide, no difference in the rates of diclofenac 4'
      hydroxylation was observed for CYP2C9 and the R144C variant regardless of OR to
      P450 ratio. However, for (S)-warfarin 7-hydroxylation, some OR-dependence was
      maintained even when the reaction was supported by cumene hydroperoxide. Finally,
      we compared CYP2C9 activity and CYP2C9 protein levels for human lymphoblast
      expressed (high OR to P450 ratio) to human liver microsomes using immunoblotting
      and enzyme selective substrates. Human liver microsomal CYP2C9 and human
      lymphoblast-expressed CYP2C9 showed comparable amounts of activity per unit
      enzyme. This final observation indicates that the high OR to P450 ratio is the
      preferred model and predicts that the R144C change in human liver microsomal
      CYP2C9 should markedly reduce the rates of substrate metabolism. The implications
      of these observations for the interpretation of results with cDNA-expressed
      enzymes is discussed.

PMID- 9241661
TI  - Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9
      ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation.
AB  - Cyclophosphamide and ifosfamide are alkylating agent prodrugs that require
      activation by cytochrome P450 (CYP) to manifest their cancer chemotherapeutic
      activity. The present study investigates the activity of four individual human
      CYP2C enzymes and their allelic variants in cyclophosphamide and ifosfamide
      activation as an initial attempt to gain insight into the underlying basis for
      the large interpatient differences in the clinical pharmacokinetics and
      metabolism of these anticancer drugs. Recombinant CYP2C8, CYP2C19, two allelic
      variants of CYP2C18, and six variants of CYP2C9 expressed in a yeast cDNA
      expression system were each enzymatically active, as judged by the ability of the
      isolated microsomes to catalyse 7-ethoxycoumarin O-deethylation after
      reconstitution with purified NADPH-cytochrome P450 reductase and cytochrome b5.
      With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed
      by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order
      was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. CYP2C18 had the highest in vitro
      intrinsic clearance/catalytic efficiency (apparent Vmax/Km) in cyclophosphamide
      and ifosfamide activation, followed by 2C19 > 2C9 approximately 2C8. Examination
      of a panel of CYP2C allelic variants revealed that CYP2C18-Thr385 had both a
      higher Vmax and a higher apparent Km toward cyclophosphamide than CYP2C18-Met385
      with no difference in catalytic efficiency, whereas with ifosfamide the Thr385
      allele exhibited a strikingly lower apparent Km resulting in a six-fold higher
      catalytic efficiency. In the case of CYP2C9, a Ile359 to Leu mutation associated
      with poor metabolism of the hypoglycemic drug tolbutamide decreased catalytic
      efficiency toward cyclophosphamide by increasing the apparent Km, whereas the
      same mutation reduced the efficiency of this P450 toward ifosfamide by decreasing
      the Vmax. Substitution of CYP2C9-Gly417 by Asp resulted in a two-fold lower
      catalytic efficiency for cyclophosphamide metabolism but a three-fold higher
      efficiency for ifosfamide metabolism. A His276 to Gly substitution resulted in an
      increase in both Vmax and apparent Km with no net change in catalytic efficiency
      for either oxazaphosphorine. Mutations at CYP2C9 residues 144 and 358 had little
      or no effect. Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km
      catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human
      CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies
      and with striking differences among naturally occurring allelic variants in the
      case of CYP2C9 and CYP2C18.

PMID- 9241662
TI  - Genetic differences in alcohol drinking preference between inbred strains of
      mice.
AB  - Genetic factors are known to influence the preference for drinking alcohol-in
      humans as well as certain inbred strains of laboratory animals. Here we examined
      the possible role of the aromatic hydrocarbon receptor (AHR) in alcohol
      preferring C57BL/6J (B6, high-affinity AHR) and alcohol-avoiding DBA/2J (D2, low
      affinity AHR) inbred mouse strains, and in the two congenic lines B6.D2-Ahrd (>
      99% B6 genome with the D2 low-affinity AHR) and D2.B6-Ahrb-1 (> 99% D2 genome
      with the B6 high-affinity AHR). This laboratory had previously shown an
      association between resistance to intraperitoneal ethanol-induced toxicity and
      the high-affinity AHR. Offering the choice between drinking water and 10%
      ethanol, we found that alcohol preference is three- to four-fold greater in B6
      than D2 mice, as well as three- to four-fold greater in B6.D2-Ahrd than D2.B6
      Ahrb-1 mice-indicating that alcohol preference is AHR-independent. The prototype
      AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) did not affect the
      rates of chronic alcohol consumption in B6 or D2 mice, suggesting that dioxin
      inducible metabolism does not play a major role in alcohol drinking preference.
      In B6 mice, we found that oral treatment with the aldehyde dehydrogenase (ALDH)
      inhibitor disulfiram decreased alcohol preference by 50%, whereas oral treatment
      of the catalase inhibitor 3-amino-1,2,4-triazole increased alcohol drinking
      preference by 15-20%. Although liver and brain ALDH activities were both
      significantly higher in D2 than B6, these activities were not related to alcohol
      consumption. Hepatic and brain catalase activities, on the other hand, were two-
      to three-fold higher in D2 and D2.B6-Ahrb-1 mice, compared with that in B6 and
      B6.D2-Ahrd. Furthermore, brain acetaldehyde levels were inversely related to the
      quantity of alcohol voluntarily consumed. We conclude that the alcohol drinking
      preference between the B6 and D2 inbred mouse strains is independent of the Ah
      receptor-but is genetically determined, in part, by the level of brain catalase
      activity which, in turn, regulates brain acetaldehyde concentrations.

PMID- 9241663
TI  - Increased frequency of a null-allele for NAD(P)H: quinone oxidoreductase in
      patients with urological malignancies.
AB  - The NQO1 locus on chromosome 16q2.2 encodes NAD(P)H:quinone oxidoreductase, an
      enzyme implicated in detoxication and protection against redox cycling. Two
      alleles have been identified in the human population, the rarer one, termed the
      null-allele, coding for a nonfunctional enzyme. Since lack of NQOR activity has
      been suggested to increase susceptibility to certain cancers, the distribution of
      the two alleles was determined by polymerase chain reaction-restriction fragment
      length polymorphism analysis in patients with renal cell carcinoma (n = 131) and
      urothelial carcinoma (n = 99) compared with a normal population (n = 260). Allele
      distribution in the normal population followed a Hardy-Weinberg distribution with
      frequencies of 0.867 for the major allele and 0.133 for the null-allele.
      Increased frequencies of the null-allele were found in the tumour patient groups
      (0.191 and 0.182, respectively) due to an increased number of both homo- and
      heterozygotes. The odds ratios for homozygous null-allele vs. wild-type genotypes
      were 1.7 and 3.6 for renal cell carcinoma and urothelial carcinoma, respectively.
      These data are compatible with the assumption that diminished activity of NQOR in
      some individuals increases susceptibility to certain cancers.

PMID- 9241664
TI  - Relationship between human genotype and phenotype of N-acetyltransferase (NAT2)
      as estimated by discriminant analysis and multiple linear regression: 1. Genotype
      and N-acetylation in vivo.
AB  - Twenty-six healthy Caucasian subjects were evaluated for polymorphic N
      acetyltransferase (NAT2) metabolic activity in vivo by sulfamethazine phenotyping
      and for their respective NAT2 genotype. Application of discriminant analysis
      allowed the separation of the rapid and slow acetylators solely on the base of
      their respective mutation pattern with identical results as achieved by the
      classical method of discrimination according to the phenotyping results. Multiple
      linear regression analysis was used to obtain a quantitative relationship between
      allelic pattern and the phenotypic outcome. It is shown that the computation
      methods produce relationships enabling the influence of particular mutations
      and/or allelic configurations on the metabolic activity in vivo to be estimated.
      This may be important in cases of discordant or overlapping phenotype and
      genotype results as well as in investigating the NAT2 polymorphism as a risk
      factor for cancer and other disease in epidemiological studies.

PMID- 9241665
TI  - CYP2A6 gene polymorphism and risk of liver cancer and cirrhosis.

PMID- 9241666
TI  - Glutathione S-transferase theta genetic polymorphism might influence tacrine
      hepatotoxicity in Alzheimer's patients.

PMID- 9241667
TI  - Environmental estrogens and reproductive health: a discussion of the human and
      environmental data.
AB  - Estrogenic activity of certain xenobiotics is an established mechanism of
      toxicity that can impair reproductive function in adults of either sex, lead to
      irreversible abnormalities when administered during development, or cause cancer.
      The concern has been raised that exposure to ambient levels of estrogenic
      xenobiotics may be having widespread adverse effects on reproductive health of
      humans and wildlife. The purpose of this review is to evaluate (a) the nature of
      the evidence supporting this concern, and (b) the adequacy of toxicity screening
      to detect, and risk assessment procedures to establish safe levels for, agents
      acting by this mechanism. Observations such as adverse developmental effects
      after maternal exposure to therapeutic levels of the potent estrogen
      diethylstilbestrol or male fertility problems after exposure to high levels of
      the weak estrogen chlordecone clearly demonstrate that estrogenicity is active as
      a toxic mechanism in humans. High level exposures to estrogenic compounds have
      also been shown to affect specific wildlife populations. However, there is little
      direct evidence to indicate that exposures to ambient levels of estrogenic
      xenobiotics are affecting reproductive health. Reports of historical trends
      showing decreasing reproductive capacity (e.g., decreased sperm production over
      the last 50 years) are either inconsistent with other data or have significant
      methodologic inadequacies that hinder interpretation. More reliable historical
      trend data show an increase in breast cancer rate, but the most comprehensive
      epidemiology study to data failed to show an association between exposure to
      persistent, estrogenic organochlorine compounds and breast cancer. Clearly, more
      work needs to be done to characterize historical trends in humans and background
      incidence of abnormalities in wildlife populations, and to test hypotheses about
      ambient exposure to environmental contaminants and toxic effects, before
      conclusions can be reached about the extent or possible causes of adverse
      effects. It is unlikely that current lab animal testing protocols are failing to
      detect agents with estrogenic activity, as a wide array of estrogen-responsive
      endpoints are measured in standard testing batteries. Routine testing for aquatic
      and wildlife toxicity is more limited in this respect, and work should be done to
      assess the validity of applying mammalian toxicology data for submammalian hazard
      identification. Current risk assessment methods appear to be valid for estrogenic
      agents, although the database for evaluating this is limited. In conclusion,
      estrogenicity is an important mechanism of reproductive and developmental
      toxicity; however, there is little evidence at this point that low level
      exposures constitute a human or ecologic health risk. Given the potential
      consequences of an undetected risk, more research is needed to investigate
      associations between exposures and effects, both in people and animals, and a
      number of research questions are identified herein. The lack of evidence
      demonstrating widespread xenobiotic-induced estrogenic risk suggests that far
      reaching policy decisions can await these research findings.

PMID- 9241668
TI  - Valproate-induced limb malformations in mice associated with reduction of
      intracellular pH.
AB  - Valproic acid (VPA) is a commonly used antiepileptic agent that recently has been
      found useful in the treatment of affective disorders and prophylaxis of migraine.
      VPA induces congenital malformations, especially spina bifida, in the offspring
      of women treated with this agent during early pregnancy. The mechanism by which
      VPA induces abnormal development remains unknown despite many studies in
      experimental animals in which VPA causes malformations similar to those seen in
      human infants. Because of its chemical structure as a weak organic acid and its
      capability to induce postaxial forelimb ectrodactyly in C57BL/6 mice, we
      postulated that VPA acts to perturb limb morphogenesis by reducing embryonic
      intracellular pH (pHi). We administered VPA, 200 to 400 mg/kg, to C57BL/6 mice on
      day 9 of gestation. A dose-dependent incidence of postaxial forelimb ectrodactyly
      was observed. Forelimb bud pHi was estimated by computer-assisted image analysis
      from the transplacental distribution of 14C-DMO. At the highest doses, 300 and
      400 mg/kg, a decrease of pHi of 0.2 to 0.3 pH units was observed uniformly
      throughout the limb bud 1 h after VPA treatment. None of these changes were seen
      after treatment with 2-en VPA, a nonteratogenic analog of VPA. Furthermore, the
      capability of VPA to induce postaxial forelimb ectrodactyly was greatly enhanced
      by coadministration of agents that inhibit pHi regulatory processes. These data
      support the hypothesis that VPA-induced postaxial ectrodactyly in murine fetuses
      can be attributed to reduction in limb bud pHi.

PMID- 9241669
TI  - Brief hypoglycemia alters morphology, function, and metabolism of the embryonic
      mouse heart.
AB  - This study examined effects of brief embryonic exposure to hypoglycemia on the
      developing mouse heart during organogenesis. Mouse embryos were exposed in whole
      embryo culture to brief periods (2, 4, or 6 h) of hypoglycemia (20, 40, or 80
      mg/dL glucose) at three developmental stages (10, 20, or 30 somites), and hearts
      were examined for morphologic, functional, and metabolic effects. Hypoglycemia
      produced abnormal cardiac structure and expansion and pericardial edema, and it
      disrupted histologic integrity and growth of the heart, particularly at 20
      somites. Embryonic heart rate was decreased by hypoglycemia at all three stages.
      Cardiac glucose uptake and glycolysis were increased by hypoglycemia, suggesting
      a compensatory response to glucose deficiency, with little effect on ATP levels.
      In summary, brief embryonic exposure to hypoglycemia affects the morphology,
      function, and metabolism of the developing heart. Mechanisms by which metabolic
      responses are related to morphologic and functional effects are currently
      unclear.

PMID- 9241670
TI  - Teratogenicity of methanol following a single oral dose in Long-Evans rats.
AB  - The teratogenicity of methanol was investigated following a single oral exposure
      preceded by an equal volume of mineral oil to guard against local gastric
      irritation. Four groups of pregnant Long-Evans rats were gavaged on day 10 of
      gestation with the following solutions: 0.0 (n = 13), 1.3 (n = 12), 2.6 (n = 11),
      and 5.2 (n = 10) mL MeOH/kg. Wilson sectioning (head only), gross necropsy, and
      Alizarin red skeletal examinations were performed on day 20 of gestation. At 5.2
      mL/kg, the dams demonstrated > 20% decrease in weight gain in comparison to the
      control, which was the only clinical toxic manifestation or histopathologic
      change noted for the dams. Methanol at all doses failed to produce any
      significant change in standard reproductive indices (e.g., postimplantation
      loss). A significant decrease in fetal body weight (11 to 19.5%), however, was
      associated with prenatal oral ingestion of methanol. Both internal and external
      examination of the fetuses demonstrated a dose-dependent increase in anomalies [0
      = 0.6%, 1.3 mL/kg = 3.7%, 2.6 mL/kg = 7%, 5.2 mL/kg = 16.5% (litter percents)].
      The dose-related anomalies were undescended testes, exophthalmia, and
      anophthalmia. Thus, acute methanol given orally produces anomalies, even when
      there is no apparent maternal toxic response.

PMID- 9241671
TI  - Toxicant-induced acceleration of epididymal sperm transit: androgen-dependent
      proteins may be involved.
AB  - Previously we established that a 4-d exposure to chloroethylmethanesulphonate
      (CEMS), a chemical that significantly reduces serum testosterone (T) levels,
      resulted in a significant decrease in cauda epididymal sperm reserves in adult
      male rats while homogenization-resistant testicular spermatid numbers were
      unaffected. This epididymis-specific alteration occurred whether or not
      circulating T levels were maintained using T-filled Silastic implants. To
      determine whether this epididymis-specific decrease in sperm number was the
      result of decreased epididymal transit time, the vas deferens was ligated at its
      midpoint just prior to the first of 4 d of exposure to CEMS with and without T
      implantation. If epididymal sperm transit was accelerated due to treatment, there
      would be fewer sperm in the caput/corpus and more sperm in the cauda/vas of the
      treated animals compared to control. The number of sperm in the caput/corpus
      decreased significantly (P < 0.05) while the number of sperm in the cauda/vas
      increased significantly in both the CEMS and CEMS + T animals. Daily sperm
      production was unaffected, but transit time through the caput/corpus epididymidis
      was decreased significantly in both treatment groups. To determine if testicular
      fluid played a role in the epididymis-specific decline in sperm numbers, the
      efferent ducts were ligated at the same time the vas deferens was ligated. Again,
      the number of sperm in the caput/corpus decreased significantly with treatment
      while there was a reciprocal increase in the number of cauda/vas sperm relative
      to controls. Finally, to determine whether an androgen-mediated process might be
      involved, the known antiandrogen hydroxyflutamide (HFLUT) was given to castrated,
      T-implanted animals in which the fertilizing ability of epididymidal sperm is
      maintained over 4 days. Once again, the number of sperm in the caput/corpus
      decreased significantly while there was a reciprocal increase in cauda/vas sperm.
      A quantitative evaluation of the protein profile in homogenates of the
      caput/corpus epididymidis revealed treatment-related diminutions in two proteins
      CC9 (M(r) = 42 kDa, pI = 4.2) and CC34 (M(r) = 35 kDa, pI = 5.5), and the level
      of each of these proteins in the caput/corpus was significantly correlated with
      the decrease in caput/corpus sperm number. Thus, both CEMS and HFLUT accelerate
      sperm transit through the proximal segment of the epididymis; and, while this
      effect is not dependent on the testis, it may involve a lesion in androgen
      dependent epididymal function.

PMID- 9241672
TI  - Flow cytometric evaluation of the effects of doxorubicin on rat spermatogenesis.
AB  - Histopathologic examination of testicular tissue allows testicular impairment to
      be investigated. As an alternative to histopathology, flow cytometry (FCM) using
      a triple staining technique that combines DNA-ploidy with mitochondria
      stainability and vimentin immunostaining has also been utilized to evaluate
      testicular damage. In this article we evaluate the effects on spermatogenesis
      after acute exposure of rats to doxorubicin. Testicular cell suspensions of
      treated and control animals were analyzed by FCM. This allows several cell types
      to be identified and quantified, giving a control pattern. Deviations from this
      control pattern are considered as an indication of testicular damage. Doxorubicin
      produced a depletion of spermatogonia as early as 3 d after treatment. This
      effect could be followed through the temporal evolution of spermatogenesis.
      Comparable results were obtained by histopathology. The presented results show
      that FCM is a suitable and sensitive method for the detection of testicular
      damage. The advantages of FCM over other techniques include its rapidity and
      objectivity.

PMID- 9241673
TI  - The influence of protein malnutrition on the antifertility action of gossypol in
      the Trypanosoma brucei-infected rat: some ultrastructural observations from the
      testis.
AB  - The testes of adult male Wistar rats that were variously protein malnourished,
      gossypol treated, and/or trypanosome infected (Trypanosoma brucei) were evaluated
      ultrastructurally. The findings included several necrotic germ cells in the
      seminiferous epithelium and focal degeneration of Sertoli cells. Leydig cells
      showed a remarkable paucity of smooth endoplasmic reticulum, and aggregation of
      mitochondria. These observations were prevalent in those animals that were
      simultaneously protein-malnourished/gossypol treated/ trypanosome infected, and
      were either absent or markedly reduced in the other groups. These structural
      alterations are probably related to increased gossypol availability to the testis
      and/or represent the additive effects of gossypol and trypanosomes. Such tissue
      changes could compromise spermatogenesis in affected animals, and suggest that
      trypanosome infections may exacerbate testicular lesions in the gossypol-treated
      rat.

PMID- 9241674
TI  - Antenatal exposure to atenolol and retroperitoneal fibromatosis.
AB  - We present a case of retroperitoneal fibromatosis in a fetus whose mother took
      atenolol during pregnancy. A 25-year-old obese woman was treated for hypertension
      with 100 mg atenolol daily from the second month until the end of pregnancy. At
      29 weeks, echography disclosed a retroperitoneal mass and at 37 weeks, a boy was
      delivered. A biopsy of the tumor showed a fibromatosis with medullary
      compression, treated by antimitotics until 3 months of age. At the age of 4, the
      mass had disappeared but severe scoliosis was present. This in utero exposure to
      atenolol drew our attention because the retroperitoneal localization of the tumor
      is similar to that of fibroses reported in adults after exposure to atenolol and
      for other reasons: transplacental carcinogenesis has been demonstrated in humans,
      at least for diethylstilboestrol, atenolol crosses the placental barrier, the
      drug was taken during nearly the whole pregnancy, and retroperitoneal
      fibromatosis is exceptional as a neonatal tumour.

PMID- 9241675
TI  - Robert L. Brent.

PMID- 9241676
TI  - Identifying teratogens: the tyranny of lists.

PMID- 9241677
TI  - The effects of antirheumatic drugs on reproductive function.

PMID- 9241678
TI  - Doubling the number of women consuming vitamin supplement pills containing folic
      acid: an urgently needed birth defect prevention complement to the folic acid
      fortification of cereal grains.
AB  - The major known environmental causes of birth defects are ancient agents that
      have been in the environment for centuries but have been only recently discovered
      rubella, alcohol, and folic acid deficiency. In the United States, we have made
      great progress in preventing congenital rubella syndrome. We also have a great
      opportunity to prevent spina bifida and anencephaly (SBA) by increasing the
      number of women who daily consume vitamin supplements containing folic acid. Even
      with the recently announced grain fortification regulations, there are 45 million
      women unprotected from an SBA-affected pregnancy. This article suggests that a
      substantial educational campaign could, over a 5-year period, double the number
      of women consuming folic acid supplement pills and make a substantial
      contribution toward preventing SBA.

PMID- 9241679
TI  - Growth as a manifestation of teratogenesis: lessons from human fetal pathology.

PMID- 9241680
TI  - Lysosomes and teratogenesis: from hypothesis to dogma and back.

PMID- 9241681
TI  - Mechanisms of amino acid supply to the rat conceptus in normal and abnormal
      development.
AB  - Using in vitro and in vivo models, we have shown that protein is an important
      source of amino acids from 8.5 to 17.5 d postconception, a significant portion of
      postimplantation development in the rat. This satisfactorily explains why
      inhibition of protein pinocytosis and digestion by the visceral yolk sac may lead
      to congenital malformations, growth retardation, and intrauterine death during
      organogenesis and growth retardation and death during fetal stages. In humans,
      this process may be just as important and possibly just as vulnerable to
      inhibition, but other placental or paraplacental tissues may be involved in
      addition to the secondary yolk sac.

PMID- 9241682
TI  - Behavioral teratologic studies using microwave radiation: is there an increased
      risk from exposure to cellular phones and microwave ovens?
AB  - The objective of the investigations presented in this review was to determine if
      there are adverse effects due to chronic prenatal microwave exposure in rats at
      term and/or alterations in neonatal and adult offspring psychophysiologic
      development and growth. Following the establishment of a nonhyperthermal power
      density level of microwave radiation, pregnant rats were exposed throughout
      pregnancy to continuous wave 915 MHz, 2450 MHz, or 6000 MHz radiation at power
      density levels of 10, 20, or 35 mW/cm2, respectively. Teratologic evaluation
      included the following parameters: maternal weight and weight gain; mean litter
      size; maternal organ weight and organ weight/body weight ratios; body weight
      ratios of brain, liver, kidneys, and ovaries; maternal peripheral blood
      parameters including hematocrit, hemoglobin, and white cell counts; number of
      resorptions and resorption rate; number of abnormalities and abnormality rate;
      mean term fetal weight. Mothers were rebred, and the second, nonexposed litters
      were evaluated for teratogenic effects. Exposed offspring were evaluated using
      the following perinatal and adult tests: eye opening, surface righting, negative
      geotaxis, auditory startle, air righting, open field, activity wheel, swimming,
      and forelimb hanging. Offspring were also monitored for weekly weight and weight
      gain. Animals exposed to 915 MHz did not exhibit any consistent significant
      alterations in any of the above parameters. Exposure to 2450 MHz resulted only in
      a significantly increased adult offspring activity level compared to nonexposed
      offspring. Offspring exposed to 6000 MHz radiation exhibited an initial slight,
      but significant, retardation in term weight, while mothers had a significantly
      reduced monocyte count. No changes in any of the other term parameters were
      observed. A few postnatal parameters were affected in offspring exposed to 6000
      MHz. Weekly weights were lower in the exposed offspring, but they recovered by
      the fifth week. Eye opening was delayed, and there were changes in the water T
      maze and open field performance levels. Several organ/body weight ratios differed
      from those of the control offspring. These results indicate that exposure to 6000
      MHz radiation at this power density level may result in subtle long-term
      neurophysiologic alterations. However, in the absence of a hyperthermic state,
      the microwave frequencies tested, which included frequencies used in cellular
      phones and microwave ovens, do not induce a consistent, significant increase in
      reproductive risk as assessed by classical morphologic and postnatal
      psychophysiologic parameters.

PMID- 9241683
TI  - Bob was right.
AB  - During his career Bob Brent has been instrumental in developing the methodology
      to use in determining whether an exposure in pregnancy has a harmful effect on
      the fetus. Experience has also shown the importance of using this approach to
      determine when an exposure is not teratogenic. Unfortunately, the attendant
      debate, as illustrated in two examples reviewed, exogenous sex hormones and
      Bendectin, requires persistence and a thick skin. Bob has recorded in several
      publications how he carried out these systematic analyses. This literature will
      be a very valuable legacy.

PMID- 9241684
TI  - Free vitamin B12 and transcobalamin II-vitamin B12 complex uptake by the visceral
      yolk sac of the Sprague-Dawley rat: effect of inhibitors.
AB  - Exogenous free vitamin B12 or B12 bound to human transcobalamin II (TCII)
      accumulated in the near-term rat visceral yolk sac. The rates of their uptakes in
      vitro and in vivo increased rapidly with time then reached a plateau, which
      supports a saturable transport/binding process as the rate-limiting step for the
      uptake of free and TCII complexed B12. Both uptakes were significantly decreased
      by trypan blue, colchicine, and low temperature but not by ouabain. Such
      inhibition suggests that the absorption of free and bound B12 is via an
      endocytosis process dependent upon energy but not the magnesium-dependent
      sodium/potassium-activated ATPase. Thus, the role of the visceral yolk sac in
      vitamin transfer to the conceptus and the alterations in yolk sac function
      associated with birth defects and diminished growth can be integrally related.

PMID- 9241685
TI  - Effect of prazosin on sperm transport in male rats.
AB  - Our objective was to investigate ejaculation and transport of sperm in the
      reproductive tract of male rats treated with an alpha-adrenergic receptor
      antagonist. Males were dosed (s.c.) with vehicle or 1.4 mg/kg prazosin. Sperm
      recovered in utero and ex vivo from the vas deferens and cauda epididymis were
      evaluated. Mating behavior and sperm motility were unaffected by prazosin.
      Prazosin treated males ejaculated fewer sperm (12.58 +/- 8.12 vs. 110.5 +/- 29.15
      million), and the distal vas deferens contained fewer sperm (2.72 +/- 0.84 vs.
      24.42 +/- 3.25 million) relative to controls. Prazosin-treated males had more
      sperm in the cauda epididymis relative to controls indicating inhibition of sperm
      transport to the vas deferens. These data demonstrate that inhibition of sperm
      transport from the cauda epididymis to the distal vas deferens is related to low
      ejaculate sperm counts in prazosin treated rats.

PMID- 9241686
TI  - Weighing the risks and the benefits: a call for the empirical assessment of
      perceived teratogenic risk.
AB  - Pregnant women are often faced with complex decisions about whether to undergo
      medical treatment or continue working in an occupational setting that is
      permeated with hazardous chemicals. The task for these women is to weigh the
      benefits of these activities against the potential risks that they may have on
      the developing embryo. Scientific uncertainty with respect to the teratogenicity
      of drugs and chemicals in humans leaves health care professionals and their
      pregnant patients with little predictive information. Cognitive research has
      shown that it is difficult for people to make complex decisions, particularly
      when the risks are uncertain. Although the problems inherent in counseling
      pregnant women regarding teratogenic risk are not new, little time has been
      devoted to the empiric assessment of how people perceive teratogenic risk and how
      teratogenic risk information can be best communicated. This article explores the
      variables that have been found, through psychometric research, to influence
      people's perception of risk and how cognitive models derived from these studies
      may be applicable to teratogen information counseling. Understanding the
      variables that shape the perception of teratogenic risk can help health care
      professionals improve how they communicate these risks to their patients.
      Improved teratogenic risk communication will result in better management of
      pregnancies and reduction of costly litigation that ensues when risks are not
      properly communicated and understood.

PMID- 9241687
TI  - Prenatal exposures to lovastatin and simvastatin.

PMID- 9241688
TI  - Sensory receptor activation by mediators of defense reflexes in guinea-pig lungs.
AB  - Histamine and bradykinin are mediators released within the lungs during lung
      defense. Both pulmonary rapidly-adapting receptors (RARs) and afferent C-fibers
      have been suggested to initiate defense reflexes evoked by these mediators.
      However, it is not known whether the sensory endings are directly stimulated by
      these mediators rather than indirectly by mechanical changes. Therefore,
      pulmonary RARs and C-fibers were challenged with aerosols of histamine,
      bradykinin and capsaicin in anesthetized guinea pigs. During histamine challenge
      tracheal pressure (PTr) and RAR nerve activity (NA) increased concurrently. After
      isoproterenol administration to attenuate increases in PTr, histamine-induced
      increases in RAR NA were similarly attenuated. Results with bradykinin or
      capsaicin challenge were similar. Therefore activation of RARs by histamine,
      capsaicin and bradykinin was dependent upon changes in lung mechanics. C-fibers
      were activated by capsaicin or bradykinin prior to any changes in PTr. However, C
      fibers were not affected by histamine challenge despite substantial increases in
      PTr. C-fibers are activated directly by either capsaicin or bradykinin but not by
      histamine.

PMID- 9241689
TI  - Depth profiles of pH and PO2 in the in vitro brainstem preparation of the tadpole
      Rana catesbeiana.
AB  - Extracellular pH and PO2 was recorded in the isolated in vitro brainstem of the
      metamorphic tadpole, Rana catesbeiana while the brainstem preparation was
      superfused with oxygenated mock cerebrospinal fluid of pH = 7.8, PCO2 = 17 Torr,
      PO2 = 600 Torr at 23 degrees C. Using pH and PO2 microelectrodes, the ventral
      medullary surface was penetrated at midline and lateral sites between cranial
      nerves V and X. Mean pH and PO2 gradients of 0.07 pH units/100 microns and 60
      Torr/100 microns were detected in the superfusate, 100-200 microns above the
      ventral surface of the brainstem. These gradients remained virtually constant for
      the first 100-200 microns below the medullary surface. Beyond this level, pH and
      PO2 gradients decreased in a curvilinear fashion. For midline tracts, minimum
      values of pH and PO2 (7.58 +/- 0.05 and 323 +/- 31 Torr) were reached at a depth
      of 500-750 microns, whereas for lateral tracts, mean minimum values of pH and PO2
      (7.34 +/- 0.12 and 240 +/- 68 Torr), were recorded at 850-900 microns. With
      further electrode advancement, pH and PO2 gradients in both midline and lateral
      tracts reversed as levels began to increase. Between CN V and X, lateral width
      was 4.34 +/- 0.57 mm, while dorsal-ventral thickness in midline and lateral
      regions was 0.92 +/- 0.21 and 1.31 +/- 0.22 mm, respectively. Overall, the in
      vitro tadpole brainstem provides a robust neural preparation which, although
      moderately acidic, is well oxygenated throughout all tissue layers.

PMID- 9241691
TI  - Effects of rapid colloid volume expansion on pulmonary microvascular pressure and
      lung water in the conscious sheep.
AB  - Increased pulmonary microvascular pressure (Pmv), in combination with other
      factors, may cause pulmonary interstitial oedema. Whether increased Pmv alone
      induces alveolar oedema is questionable. In the present study we used the heavy
      water-indocyanine green dilution method to measure lung water during a rapid
      intravascular volume expansion in the sheep. Eight conscious sheep were given two
      10-min intravenous infusions of either 50 ml/kg (N = 2) or 35 ml/kg (N = 6) of
      dextran 60 with an interval of 10 min between them. At a Pmv of 40 mmHg,
      respiratory distress was observed in sheep no. 2 which had been given a total
      amount of 100 ml/kg of dextran; this was immediately followed by a lethal
      pulmonary haemorrhage. Mean Pmv in the remaining seven sheep increased to 31 (7)
      mmHg in response to the volume expansion without causing any respiratory distress
      or increase in lung water. These results show that in conscious sheep the lungs
      have strong protective mechanisms against hydrostatic oedema. They do not support
      the hypothesis that increased Pmv alone induces alveolar oedema, but suggest that
      an increase in Pmv to 40 mmHg may cause stress failure of the pulmonary
      vasculature.

PMID- 9241690
TI  - Sleep apnea-like syndrome induced by nitrous oxide inhalation in normal men.
AB  - To study the relationship between sedation and respiration under N2O, we
      performed polysomnographic recordings in 15 healthy men with documented normal
      breathing patterns during sleep. In a first study in five subjects, we found that
      50% N2O in O2 compared to 50% O2 increased sleep latency to stage 2 (59 +/- 12
      vs. 17 +/- 3 min), total sleep duration (59 +/- 12 vs. 26 +/- 11 min), depth of
      sleep and respiratory events during sleep (18 +/- 5 vs. 1 +/- 1/h of sleep). In a
      second study, ten subjects were exposed to N2O (30 and 50%) in O2 during two
      consecutive experimental periods. Eight subjects had EEG features of
      physiological sleep, but nevertheless exhibited a total of 181 respiratory
      events. Respiratory disturbance index (RDI) during sleep was similar under 30 and
      50% N2O (25 +/- 7 and 25 +/- 5/h of sleep, respectively). Obstructive events
      predominated, except in three subjects during N2O 30% and one during N2O 50%
      exposure. We conclude that N2O can induce central and obstructive sleep apneas.

PMID- 9241693
TI  - Effects on pulmonary function of daily exposure to dry or humidified hyperbaric
      oxygen.
AB  - The purpose of this study was to examine the effects of breathing dry or
      humidified hyperbaric oxygen on pulmonary function. Pulmonary function tests were
      performed before and after each of 10 hyperbaric oxygen exposures at 2.5
      atmospheres absolute (ATA) for 95 min in a group of 13 patients treated daily by
      hyperbaric oxygen for problem wounds. Patients breathed dry oxygen during five
      successive sessions and humidified oxygen during the remaining five. No
      differences were found between forced vital capacities (FVC) and maximal
      expiratory flows before and after hyperbaric oxygen exposure while breathing dry
      or humidified oxygen. Significant differences were found for the changes in the
      percentage of FVC expired in 1 s (FEV1%) and mean forced mid-expiratory flow rate
      during the middle half of the FVC (FEF25-75%) on day 1 alone: decrements of 1.42
      and 2.96%, respectively, under dry oxygen, vs. increments of 3.93 and 34.4%,
      respectively, for humidified oxygen. Day-to-day decrements in the percent changes
      in FEV1% and FEF25-75% were observed while breathing humidified hyperbaric
      oxygen. These results demonstrate that repeated daily exposure to humidified
      hyperbaric oxygen abolishes the initial beneficial effect of humidification on
      peripheral airways flow characteristics.

PMID- 9241692
TI  - HMT regulates histamine-induced glycoconjugate secretion from human airways in
      vitro.
AB  - To determine whether histamine N-methyltransferase (HMT) regulates mucus
      glycoprotein (MGP) secretion from airways, we examined the effect of an HMT
      inhibitor, SKF 91488, on MGP secretion from human airways in vitro. MGP secretion
      from human airway explants (with epithelium) and isolated submucosal glands was
      estimated by measuring trichloroacetic acid (TCA) precipitable glycoconjugates
      using secretory indices. Histamine induced significant MGP secretion from both
      explants and isolated glands. Pretreatment with SKF 91488 significantly inhibited
      histamine-induced secretion from explants, while it did not alter significantly
      the secretion from isolated glands. H1-blocker significantly reversed the
      inhibition by SKF 91488 of the secretion from explants, while H2-blocker
      abolished histamine-induced secretion from both explants and isolated glands.
      Prostaglandin E2 (PGE2) significantly inhibited histamine-induced secretion from
      isolated glands. The inhibitory action of SKF 91488 in airway explants was
      blocked by indomethacin and was significantly reduced by a prostanoid EP4
      receptor antagonist (AH23848B). These findings suggest that HMT regulates MGP
      secretion from human airway submucosal glands through an interaction with
      epithelial cells which involves the release of PGE2.

PMID- 9241694
TI  - Respirometer for small samples with automatic registration.
AB  - The respiration chamber containing the sample is a small glass test tube with a
      closure of KOH solution. During registration the gas volume is kept constant by
      adjusting the pressure through a feedback mechanism: a microscope projects the
      picture of the meniscus of KOH onto a photodiode connected to a pen recorder with
      a vertically moving pen. A levelling bulb with water mounted on the pen transmits
      the pressure adjustments to the KOH solution through a water filled tubing. The
      accuracy is +/-0.1 mm water column (1 Pa) and the minimum air volume is 10 nl, so
      that an oxygen consumption down to 1 pl can be seen.

PMID- 9241695
TI  - What is the long term value of multiphasic health screening and the initial
      judgement of benefit?
AB  - The long term effects of multiphasic health screening (MHS) are rarely studied.
      In 1964 a random sample of 546 women and 544 men born 1899, 1904, 1909, 1914 or
      1919 equally distributed on cohorts from the Swedish town Eskilstuna were invited
      to examination. For several reasons 167 persons (15%) did not participate in the
      study. In 1969 the whole sample was invited to a second MHS together with a
      control group that had not been exposed to MHS. Furthermore, 79 of those alive
      1989 born 1899 or 1904 and examined 1964 and 1969 were reexamined. Over all
      survival rate 1989 for those examined 1964 was for males 18% and for females 35%.
      Screening instruments 1964 and 1969 were questionnaires, laboratory tests,
      antropometric measurements, ECG, measurement of blood pressure, chest
      radiography, peak expiratory flow (PEF), tonometry and fundoscopy of the eyes,
      audiometric screening, dental, gynecological and general clinical examination.
      Systolic hypertension for both sexes, low PEF and smoking, low cholesterol in
      women were negatively related to survival. Of 18 diabetics only one was alive at
      follow-up. No association was found between BMI and mortality for men, but some
      (1964 p < 0.01; 1969 p < 0.05) for women. Altogether 87 individuals were 1969
      judged to have had some benefit of the MHS in 1964, 40 of them substantial. This
      was, however, not statistically significantly associated with improved survival.
      Of the reexamined survivors 86% reported to be generally satisfied with their
      life situation. The prognostic value of graded benefit was analysed in some
      detail. The survival to age 85 in the group allotted any benefit was somewhat
      less good (37%) than in the group with no benefit (44%). The difference did not
      reach statistical significance.

PMID- 9241697
TI  - Functional capacity and health of elderly people--the Evergreen project.
      Background, design and methods of the project.

PMID- 9241696
TI  - Socio-economic status, health and life-style in two elderly cohorts in Jyvaskyla.

PMID- 9241698
TI  - Changes in physical characteristics and body composition during 5-year follow-up
      in 75- and 80-year-old men and women.
AB  - A five-year longitudinal study was conducted to examine the changes observed in
      the physical characteristics and body composition assessed by bioimpedance in 75-
      and 80-year-old men and women. During the follow-up, there was a systematic
      decline in body height in all groups studied, the mean changes being somewhat
      higher in women (1.3-1.6 cm) than in men (0.9-1.1 cm). Body weight and lean body
      mass declined in women in both age groups and in men in the younger group,
      whereas no significant changes were observed in the 80-year-old men. The relative
      proportion of body fat did not change with increasing age in any of the groups
      studied. Among 80-year-olds, the men participating in the follow-up showed some
      tendency to have more fat in the baseline than those who subsequently died, while
      the corresponding group of women tended to be somewhat taller than the other drop
      outs. The results support the earlier observations on the age-related decrease in
      body height, and in the case of women, also on reduced body weight and lean body
      mass with old age.

PMID- 9241699
TI  - Changes in physical capacity and sensory/psychomotor functions from 75 to 80
      years of age and from 80 to 85 years of age--a longitudinal study.
AB  - The purpose of the study was to describe the performance of initially 75- and 80
      year-old men and women in physical, sensory and psychomotor tests, to analyse
      longitudinal changes in these measures over a five-year follow-up period, and to
      ascertain if the performance in these measures is predictive for survival. At
      baseline, all 75- and 80-year-old men and women living in the town of Jyvaskyla
      (n = 663) were invited to participate in the study. Five years later those who
      had participated at baseline, survived and were still resident in Jyvaskyla (n =
      432) were again invited. As expected, a better performance in men than in women
      was found in tests of maximal walking speed, stair mounting and maximal isometric
      muscle strength in both age groups. Men also had better performance in
      psychomotor tests and visual acuity whereas auditory functions and postural
      balance were on average better in women. In some measures the longitudinal
      changes in five years were more pronounced than suggested by the cross-sectional
      comparisons between the 75- and 80-year-olds at baseline (e.g. psychomotor
      speed). In some others the longitudinal changes were smaller than expected on the
      basis of the cross-sectional comparisons (e.g. isometric muscle strength). In
      sensory functions longitudinal changes corresponded well with the results of the
      cross-sectional comparisons. Poor physical capacity at baseline was a significant
      predictor of subsequent death during the follow-up among the women but much less
      among the men. For both sexes a low psychomotor speed at the baseline was
      indicative of a poor survival. It is concluded that the correspondence of the
      results obtained in cross-sectional comparisons with longitudinal changes varies
      from one function to another. This correspondence may also be influenced by
      mortality which is differentially associated with the physical, sensory and
      psychomotor functions analysed in the present study.

PMID- 9241700
TI  - Cognitive functioning of 75- and 80-year-old people and changes during a 5-year
      follow-up.
AB  - The aim of the study was to analyze cognitive functioning among two cohorts of
      elderly people, aged 75 and 80 years at baseline, and changes in the functioning
      during a five-year period. Cognitive functioning was assessed using psychometric
      tests, neuropsychological tasks, metacognitive self-evaluations, cognitive
      screening tests and reaction time tasks. The objective methods correlated
      significantly with each other, and only one general factor was clearly produced
      by the factor analyses. However, the speed of cognitive processing was concluded
      to have a central meaning in the kind of assessments used in this study.
      Selective attrition affected the results of psychometric and neuropsychological
      methods; subjects with better cognitive functioning participating in the follow
      up assessments. Among those retested, the cognitive level decreased
      significantly, but the magnitude of the decline was usually low. Differences
      between the men and the women were mostly nonsignificant. The retest correlations
      were high in the psychometric tests but lower in many of the neuropsychological
      and metacognitive methods. Connections between the metamemory scores and the
      objective test scores were variable.

PMID- 9241701
TI  - Depressed mood among the elderly in Jyvaskyla. A five-year follow-up.
AB  - The aim of this article is to describe the changes that occurred in depressive
      symptomatology over a five-year period among 75- and 80-year old residents of
      Jyvaskyla. It also addresses the question of whether the mood disturbance
      detected is a permanent phenomenon or whether it has a more episodic nature. In
      both follow-up cohorts, depressed people were interviewed to find out how the
      elderly themselves experienced depression and to assess the validity of the CES-D
      self-rating scale in measuring depressive symptomatology. The purpose of the
      study was also to find out if depression was predictive for survival. During the
      five-year follow-up the mean score describing depressed mood (CES-D total scale)
      did not significantly change in any age group or gender, nor did the mean score
      of those who died during the follow up differ significantly from the core of the
      survivors. The mean score of the CES-D subscale Lack of well-being increased
      among 80-year old women over a five-year follow-up period and those who died had
      a significantly lower well-being score than those who survived. More than half of
      the interviewees were classified depressed in both age-cohorts in both
      examination times. Almost all those elderly people whose score indicated
      depressiveness in the second examination confirmed that the diagnoses of
      depressed mood based on the CES-D scale was correct. The higher the CES-D score,
      the more frequent and/or the more difficult were the problems mentioned in their
      narratives of depression. Compared with the situation at baseline, the proportion
      of men and women aged 80 who reported loneliness increased significantly during
      the follow-up.

PMID- 9241702
TI  - Morbidity and disability in 75- and 80-year-old men and women. A five-year follow
      up.
AB  - Purpose of this report is to describe the changes that occurred in morbidity,
      symptoms of illness and disability of 75- and 80-year-old residents of Jyvaskyla,
      Finland, over a five-year period. The study population consisted of the elderly
      residents of the city of Jyvaskyla in central Finland who were born in 1914 and
      1910. At baseline (in 1989 and 1990), 355 (92.9%) persons from the younger age
      group and 262 (91.9%) from the older age group were interviewed and 311 (81.4%)
      and 230 (80.7%), respectively, took part in the physical examination. At follow
      up (in 1994 and 1995), the corresponding numbers were 250 (93.3%) and 148 (88.6%)
      for the interviews and 217 (81.0%) and 127 (76.0%) for the physical examinations.
      The prevalence of chronic conditions was determined in connection with the
      medical examinations on the basis of self-report and the respondent's
      prescriptions and medical information cards. To measure the occurrence of
      symptoms, the respondents were asked whether during the past 14 days they had
      suffered from any of 17 listed symptoms. Functional capacity was assessed in
      connection with the interview carried out at the respondent's home in terms of
      needing help in activities of daily living (ADL). In the baseline examinations,
      subjects were found to have on average 2-3 diseases. During the follow-up the
      number of diseases and the proportion of people with co-morbidity increased in
      both age groups. Both men and women had on average 1-2 symptoms that caused them
      much trouble, and the number of such symptoms increased to some extent during the
      follow-up. The proportions of those needing help increased during the follow-up
      in all groups and the increase was most prominent among the women of the older
      age group. Of those who managed independently with physical ADL (PADL) at
      baseline, 14.9%-44.9% reported need of help in at least one task at follow-up.
      The need for help in PADL was greatest with cutting toe-nails, negotiating
      stairs, moving outdoors, washing the upper body and in instrumental ADL (IADL)
      with vacuuming, shopping, handling finances and in the use of public transport.
      Successful prevention and postponement of functional disabilities in the elderly
      population depends not only on the early diagnosis of illness but also on
      identifying even minor signs and symptoms of disease and functional limitations,
      and to focus health care interventions accordingly.

PMID- 9241703
TI  - Introduction: hypercoagulable states.

PMID- 9241704
TI  - Risk factors for venous thrombosis: prevalence, risk, and interaction.
AB  - Annually, 1 in 1,000 individuals is affected by venous thrombosis. Risk factors
      that are known to increase the risk of thrombosis may be either genetic or
      acquired, or have a combined origin. Many of these risk factors are very
      frequent, among which several have been recently identified, such as resistance
      to activated protein C by factor V Leiden, hyperhomocysteinemia, high levels of
      factors VIII, as well as the classical acquired risk factors, such as surgery and
      malignancies. When the prevalence of risk factors is high, it becomes likely that
      in some individuals two or more risk factors will be present simultaneously. The
      question "What happens to the risk in these circumstances?" is one involving
      interaction, also known as effect modification or synergy. In this article we
      review the prevalence and risk estimates for the various genetic and acquired
      risk factors for venous thrombosis, discuss the concept of interaction, and give
      an overview of the evidence for interaction of these risk factors.

PMID- 9241705
TI  - Antithrombin and its inherited deficiency states.
AB  - Antithrombin is the primary inhibitor of thrombin that also inhibits many of the
      other activated serine proteinases involved in blood coagulation. A
      hypercoagulable state occurs when a deficiency of antithrombin exists in plasma;
      the deficiency may be either inherited or acquired. This failure to regulate
      adequately the activity of coagulation proteinases can, with additional
      provocation, result in clot formation and in the clinical presentation of
      thromboembolic disease. The structure and function of antithrombin, nature and
      heterogeneity of the molecular defects in the antithrombin gene associated with
      inherited antithrombin deficiency, prevalence and the natural history of
      inherited antithrombin deficiency are all reviewed here.

PMID- 9241706
TI  - Protein C and protein S deficiencies.
AB  - The protein C (PC) pathway, with its cofactor protein S (PS), is an important
      natural antithrombotic mechanism. Both PC and PS deficiencies have been
      implicated in thrombophilia. The molecular basis for hereditary PC and PS
      deficiencies is highly heterogeneous, with a large spectrum of mutations that
      have various effects on the expression of the relevant allele. A small subset of
      patients who are homozygous or compound heterozygous for a PC gene mutation have
      severe thrombotic complications at birth, whereas onset occurs later in the other
      cases. Patients heterozygous for a PC or PS gene abnormality may develop
      recurrent thrombosis during adulthood, with a probability of remaining free of
      thrombosis of about 50% at age 45. A PC or PS gene defect is associated with the
      factor V Arg 506 to Gln mutation in 10% to 30% of symptomatic patients,
      suggesting that clinical expression is controlled by several genes in
      heterozygous patients.

PMID- 9241707
TI  - Resistance to activated protein C as risk factor for thrombosis: molecular
      mechanisms, laboratory investigation, and clinical management.
AB  - Protein C (PC) is the key component of a natural anticoagulant pathway that is
      activated on the surface of endothelial cells by thrombin bound to
      thrombomodulin. Activated protein C [APC] cleaves and inhibits membrane bound
      factor Va and factor VIIIa, which leads to specific and efficient downregulation
      of the coagulation pathway. In these reactions, protein S (PS) and intact factor
      V (FV) function as cofactors to APC. Inherited deficiencies of PC, PS, or
      antithrombin were until recently the major genetic causes of familial venous
      thrombophilia, but they were found in less than 5% to 10% of patients with
      thrombosis. The situation changed dramatically with the description in 1993 of
      resistance to APC as a major risk factor for venous thrombosis. Inherited APC
      resistance, which is found in 20% to 60% of patients with venous thrombosis, is
      caused by a single point mutation in the FV gene predicting substitution of
      arginine [R] at position 506 with a glutamine (Q). The mutation, which is the
      result of a founder effect, is common in Caucasians with 1% to 15% prevalence in
      the population, whereas it is not found in other human races. Mutated FV
      (FVR506Q, FV:Q506 or FV Leiden) has normal procoagulant properties but shows
      partial resistance to APC, which results in a hypercoagulable state conferring a
      lifelong increased risk of thrombosis. As a result of its high prevalence, the FV
      mutation is not uncommon among patients with other inherited defects such as
      deficiency of PS, PC, or antithrombin. Those having combined defects have a
      higher incidence of thrombosis, and it is now recognized that severe
      thrombophilia is a typical multigenetic disease. The high prevalence of the
      FVR506Q mutation and the availability of easy functional and genetic tests will
      profoundly influence the development of therapeutic and prophylactic regimens and
      will probably result in a decreased incidence of thromboembolic events.

PMID- 9241708
TI  - Combination of activated protein C resistance and antibodies to phospholipids in
      the development of thrombosis.
AB  - An insufficient response to activated protein C (APC) resistance and antibodies
      against phospholipids (PLa) are frequent laboratory findings associated with
      thrombosis. Studies investigating the coexistance of these two factors in
      thrombophilic patients and in patients with autoimmune disorders are summarized.
      The investigation of thrombophilic patients has revealed PLa in 35%. About half
      of these patients had a combination of PLa and APC resistance proved by the
      Arg506-Gln mutation in factor V (FV). A combination of APC resistance with PLa in
      this group of patients did not increase the risk of thrombosis recurrence. In the
      PLa-positive patients with autoimmune disorders having thrombosis in 10% to 56%,
      the incidence of the Arg506-Gln mutation in FV was significantly lower and varied
      between 2% and 9%. A known ability of PLa to induce APC resistance experimentally
      was often a reason to avoid the determination of APC response in PLa-positive
      patients. We suggest that PLa may play a dual role in the development of
      thrombosis in the carriers of the Arg506-Gln mutation in FV. On the one hand,
      PLas favor thrombosis by maintaining the APC response at a constantly low level.
      On the other hand, preventing the interaction of coagulation proteins on the
      phospholipid surface PLa may protect them from hypercoagulation.

PMID- 9241709
TI  - Regulation of thrombin formation by activated protein C: effect of the factor V
      Leiden mutation.
AB  - Activated Protein C (APC) resistance, one of the most common genetic risk factors
      for venous thrombosis, is caused by a single base mutation (G1691-->A) in the
      factor V (FV) gene resulting in the replacement of Arg506 by Gln at a predominant
      cleavage site for APC. Great progress in understanding the mechanism of
      downregulation of FVa activity via the protein C pathway has been achieved by
      studying APC-mediated inactivation of FVa purified from homozygous APC-resistant
      individuals. This review briefly summarizes the role of FVa in prothrombin
      activation and the structure-function relationship of FV and FVa. Subsequently,
      APC-dependent inactivation of FVa and FVa Leiden and its modulation by protein S
      and factor Xa in model systems containing purified proteins is discussed. FV also
      has a function in increasing the inactivation of FVIII/VIIIa by APC. This
      cofactor activity appears diminished in FV Leiden. Thus, an intricate mechanism
      of regulation of thrombin formation via the protein C pathway is starting to
      emerge. Extensive studies in plasma milieu will be needed to gain more insight
      into the relation between the presence of FV Leiden and impaired downregulation
      of thrombin formation in APC-resistant individuals.

PMID- 9241710
TI  - Familial thrombophilia: a complex genetic disorder.
AB  - Familial thrombosis has long been considered as an autosomal dominant trait,
      caused by a dominant gene defect with a reduced penetrance for the disease.
      Recently, this view has changed and today familial thrombophilia is considered as
      a complex genetic disorder caused by the segregation of two or more gene defects
      (known and unknown) in a family. Here we briefly discuss the known genetic
      defects (protein C, protein S, and antithrombin deficiency and activated protein
      C resistance associated with factor V Leiden) with special focus on the relation
      between gene mutation and plasma abnormality and on the association between
      abnormality and thrombosis in affected families and in the population. Finally,
      the evidence is reviewed that indicates familial thrombosis as an oligogenetic
      disorder and on the basis of these data strategies are discussed for the
      identification of new genetic risk factors for thrombosis via a genetic approach.

PMID- 9241711
TI  - End-stage renal disease.

PMID- 9241712
TI  - Anemia, hypertension, and myocardial dysfunction in end-stage renal disease.
AB  - Cardiovascular disease remains the major cause of mortality in patients with end
      stage renal disease (ESRD). The pathophysiology of cardiac dysfunction in ESRD is
      complex and not fully understood. However, it appears that the two major
      determinants of left ventricular (LV) hypertrophy and dysfunction are anemia and
      hypertension, both of which are very common in ESRD patients. Early and
      aggressive correction of anemia and hypertension may have a significant impact on
      cardiac disease in ESRD patients. This article presents a discussion on the
      management of anemia and hypertension, and the current information available on
      the pathogenesis and management of LV dysfunction in ESRD.

PMID- 9241713
TI  - Use of erythropoietin, active vitamin D3 metabolites, and alkali agents in
      predialysis patients.
AB  - Studies in rats with renal ablation indicate that anemia lessens, whereas its
      vigorous correction with recombinant human erythropoietin (r-HuEPO) worsens
      systemic and glomerular hypertension, factors known to promote progression of
      chronic renal failure (CRF). However, in human studies, use of r-HuEPO in
      predialysis patients has not been associated with worsening renal function,
      provided blood pressure control is achieved. Histological evidence of bone
      disease is common in early renal failure, and deficits in calcitriol synthesis
      seem to be an important factor in the pathogenesis of secondary
      hyperparathyroidism (HPTH) in early CRF. Reports to data, on the use of low dose
      active vitamin D metabolites in predialysis patients, indicate either a
      reversible decline or no decline in renal function. Adynamic bone disease,
      however, may ensure during such therapy if excessive reductions in serum intact
      parathyroid hormone concentrations occur. Recent data suggest that chronic
      metabolic acidosis decreases albumin synthesis, increases muscle proteolysis, and
      induces negative nitrogen balance in patients with CRF. Despite these
      experimental data, the clinical relevance of correction of metabolic acidosis in
      end-stage renal disease (ESRD) is still not defined. Even though therapy of
      metabolic acidosis in the adult patient with CRF remains conjectural at this
      time, reports indicate that its correction might lead to healing of osteomalacia
      and osteopenia, and possibly may decrease protein degradation and improve growth
      in children with CRF.

PMID- 9241714
TI  - Optimizing the treatment of the dialysis patient: a painful lesson.
AB  - Our current understanding of how dialysis should be measured and optimized
      evolved from several painful lessons. The pain was felt by patients who were
      passive recipients of treatments that were often limited by the toxic effects of
      acetate, attempts to shorten treatment time, and adverse effects of the
      membranes. Pain was also felt by caregivers who were burdened by the
      complications of inadequate dialysis that required their efforts and vigilance.
      Early efforts to quantify dialysis by controlling the serum urea concentration
      were replaced by methods to control the dialyzer urea clearance expressed per
      dialysis and factored for the patient's size (Kt/V). This understanding resulted
      largely from data collected during US National Cooperative Dialysis Study in the
      late 1970s, but it took several years for the lesson to become a standard of
      practice. We continue to struggle with our understanding of uremic toxins and how
      best to remove them. The future promises to resolve the age-old question of
      toxicity and to give us a better perspective on the effects of protein
      catabolism, residual renal clearance, and both dialysis duration and frequency.
      Other factors yet to be explored may ultimately impact on the requirement for
      dialysis and allow better tailoring of treatment to individual needs.

PMID- 9241715
TI  - The dialysis facility of the future: the financial and social environment.
AB  - Changes in the delivery of care are being driven by the rapid advance of managed
      care. Nephrologists must continue to be advocates for the end-stage renal disease
      (ESRD) patient in a medical environment obsessed with costs. Reorganization of
      nephrology will be mandatory because capitation is on the immediate horizon. Fee
      for-service care will diminish, and nephrologists must learn how to become the
      driving force for quality care in a cost-effective environment. The formation of
      nephrology Independent Practice Associations (IPAs) will create the structure
      that allows nephrologists to negotiate and accept global captitated contracts for
      ESRD care. Placing the patients' interests first will ultimately lead to reduced
      costs. Changes in the nephrology workforce over the next decade will dictate
      participation in a horizontal and vertical integration team approach to care of
      the patient with ESRD.

PMID- 9241716
TI  - Acute dialysis and continuous renal replacement: the emergence of new technology
      involving the nephrologist in the intensive care setting.
AB  - The emergence of dialytic support for patients with reversible renal failure was
      one of the most significant advances in critical care medicine. Supporting a
      patient with a failed organ till organ recovery has not had the same success with
      other organ failures. Despite the indispensable nature of the support, dialysis
      was intermittent at best, and carried its own morbidity. The emergence of a
      "continuous" dialysis delivery system, originally through an arteriovenous access
      and later through veno-venous methodology, began to simulate the continuity of
      the natural kidney, and lifted much of the fluid and drug restrictions imposed by
      the intermittent nature of standard dialytic therapies. Components of the system
      were next reviewed for improvement and biocompatability. Differences in patient
      outcome were documented with various component comparisons, and disparate patient
      tolerance of delivery modality was also clearly proven. The hemodynamic stability
      of continuous treatment created utilization to be focused on the more unstable,
      the more severely compromised patient group. In this context, comparative studies
      with intermittent delivery methods showed improved hemodynamic stability among
      patients treated with continuous renal replacement therapies (CRRT), but no clear
      difference in patient mortality. Patient characteristics and severity scoring
      have recently been undertaken to better describe the population, and attempts at
      dialysis dosing is currently being developed for ARF dialysis recipients. Early
      results seem to point toward a dialysis dose effect on mortality in certain
      groups of ICU acute renal failure patients. However, the dialytic process is only
      depurative and artificial. Plastic membrane bio-incompatibility, human
      physiological responses to foreign material exposure, either in the circuit
      material itself or introduced from therapy methodology, pose practical and
      theoretical problems. Recent advances in the field of bio-artificial technology
      have allowed the development of functioning hybrid "blood processors," which
      function as a renal tubule and may be able to not only "clean" blood, but also
      allow for other cellular functions not currently possible with dead membrane
      technology. Combining living cells with a continuous delivery method may be the
      next significant step toward a fully functional renal replacement therapy.

PMID- 9241717
TI  - The technology of dialyzer reuse.
AB  - Dialyzer reuse has become an integral part of chronic hemodialysis in the United
      States of America because it has large economic benefits which allow the use of
      expensive, biocompatible membranes, and the delivery of adequate dialysis therapy
      in the face of continued inflation of costs and fixed reimbursement. The conflict
      between patient safety and provider economic benefit has been resolved by the
      development of recommended practice guidelines by the Association for the
      Advancement of Medical Instrumentation. When followed carefully, disinfection of
      dialyzers for multiple reuse by the same patient is relatively safe and effective
      in eliminating infection, pyrogen reactions, and other potential complications
      associated with germicide use. However, despite all precautions, there appears to
      be consequences of certain germicides, such as formaldehyde, that are difficult
      to eliminate, such as anti-N antibody. The development of heat or heat and 1.5%
      citric acid would appear to eliminate all these problems, and offers a safe,
      effective, and cost saving method for reuse of polysulfone dialyzers. Allegations
      of increased mortality with certain germicides, reuse techniques, and treatment
      settings, as well as the contribution of reuse to inadequate dialysis remain
      unproven and require further investigation.

PMID- 9241718
TI  - Optimizing end-stage renal disease therapy for the patient with diabetes
      mellitus.
AB  - Patients with diabetes represent the fastest growing segment of the end-stage
      renal disease (ESRD) population, which itself is growing at a rate of
      approximately 10% per year. The most recent report of the United States Renal
      Data System (USRDS) shows a prevalence of diabetes among patients with ESRD of
      27.3% (59,403 of 217,479) and an incidence of 33.6% (19,013 of the 56,610). The
      majority of patients with ESRD secondary to diabetes (67.7%) are treated by
      hemodialysis, 13.2% by peritoneal dialysis, and 19.1% have functioning renal
      transplants. The number of patients over 60 years of age has increased steadily.
      Parallel with this increase, the percentage of patients with one or more comorbid
      conditions increased from 66% to 85% in patients with diabetes and from 57% to
      66% in patients without diabetes. The relative risk of death in patients with
      diabetes is markedly increased and is further exacerbated in patients with poor
      nutritional status. Although diabetes is the most common primary disease
      associated with death in the ESRD population, the mortality for patients with
      ESRD secondary to diabetes has decreased from 46% in 1982 to 29% in 1993.
      Patients with ESRD from diabetes challenge the nephrologist because they have the
      greatest number of comorbid conditions, the highest levels of physical
      dysfunction, and the greatest dependency in activities of daily living. The goal
      of therapy is to improve quality of life, as well as reduce mortality. Patients
      with diabetes experience improved survival after either kidney transplant or
      enhanced Kt/V on dialysis. Therefore, the most important therapeutic intervention
      is to maximize renal replacement therapy (either by transplantation or by
      providing levels of dialysis adequacy higher than previously recommended). In
      addition, attention to several basic principles helps to guide therapy; control
      of hypertension, control of hyperglycemia, control of lipid abnormalities,
      treatment of malnutrition, and attention to the effects of erythropoietin.
      Advanced glycation and products (AGEs) have been proposed as new "uremic toxins",
      because of their pathogenetic association with a variety of vascular and morbid
      complications. There is sound experimental evidence to suggest that reducing the
      accumulation of these products to normal levels may prevent diabetic
      complications. Better understanding of the nature of the relationship between
      formation and removal is needed to direct therapeutic interventions towards
      adequate control of the accumulation of AGEs in patients with renal failure, with
      or without diabetes.

PMID- 9241719
TI  - A 1990s perspective of hepatitis C, human immunodeficiency virus, and
      tuberculosis infections in dialysis patients.
AB  - Chronic infections contribute significantly to morbidity and mortality in
      dialysis patients. These infections are acquired either before or after
      initiation of dialysis, and the latter may be via nosocomial modes of
      transmission. Consequently, policies that deal with infection control in dialysis
      units have assumed increasing importance. The incidence and prevalence of
      hepatitis C virus (HCV) infection among patients on dialysis is steadily
      declining. Nonetheless, the 0.4% to 15% incidence of anti-HCV in hemodialysis
      (HD) units continues to be a cause for concern. Although nosocomial transmission
      of HCV infection in HD units has been demonstrated, the Centers for Disease
      Control and Prevention (CDC), Atlanta, GA, does not recommend dedicated machines,
      patient isolation, or a ban on reuse in HD patients with HCV infection.
      Conventional cleansing and sterilization procedures for reprocessing the
      dialyzers appear to be adequate to inactivate the virus. Over the years, there
      has been a steady increase in the number of human immunodeficiency virus (HIV)
      infected patients entering end-stage renal disease (ESRD) programs. Transmission
      of HIV infection is extremely unlikely in dialysis units that conform to the
      standard practice guidelines. Dedicated machines or isolation from other patients
      are not recommended for patients with HIV infection. Risk of acquiring HIV
      infection after an occupational exposure is approximately 0.32%. Nonetheless, a
      combination of zidovudine and lamuvidine for most parenteral exposures, and the
      addition of a protease inhibitor in high-risk exposures, is recommended. The wide
      range of immunological derangements in chronic renal failure have been postulated
      to be the cause for the increased susceptibility of dialysis patients to
      tuberculosis (TB). The high incidence of extrapulmonary disease may be a
      significant factor in the delay in diagnosis of TB in these patients. In view of
      their high-risk for exposure to TB, the purified protein derivative (PPD) skin
      test is recommended on an annual basis in the staff of dialysis units.

PMID- 9241720
TI  - The evolution and future of immunosuppression in renal transplantation.
AB  - Since the early 1960s, a number of new immunosuppressive agents have been
      introduced to clinical transplantation. This review will be confined to mechanism
      of actions, and important gains and concerns of new microemulsion formulation of
      cyclosporine A (Neoral), mycophenolate mofetil (MMF), FK506, brequinar sodium,
      sirolimus (rapamycin), leflunomide, and 15-deoxyspergualin. We will also review
      some of the recent studies with monoclonal antibodies.

PMID- 9241721
TI  - Expanding the donor pool.
AB  - Advances in techniques and the development of new immunosuppressive drugs have
      made it possible to transplant a large number of patients throughout the world.
      However, the shortage of cadaveric organ donors remains the major obstacle for
      the full development of organ transplantation, imposing a severe limit to the
      number of patients who could benefit from this therapy. Although transplants save
      thousands of lives and transform the quality of life of thousands more, many
      people will die or remain on renal replacement therapy because the organ supply
      falls drastically short of actual demand. In the US, the number of organ donors
      has increased approximately 20% over the past 5 years, but this increase has been
      brought about largely by the use of older donors and other donors considered by
      some to be marginal. In the 6 years from 1988 to 1994, the waiting list for
      kidneys grew by 76% in the US. By the end of August 1996, there were 33,339
      patients registered for kidneys on the national transplant waiting list. This
      report examines the issue of the elderly donor, the role of living-unrelated
      kidney transplantation, and proposes various strategies to enhance procurement of
      cadaver kidneys.

PMID- 9241722
TI  - Prospects for a bioartificial kidney.
AB  - The developing technologies of cell therapy and tissue engineering may, in the
      next two decades, provide alternatives to current methods of renal replacement
      therapy. First, suitable organs for xenotransplantation from animals to humans
      may be developed, or second, as described in this report, application of tissue
      engineering may result in development of a range of devices to aid care of
      patients with renal failure. The simplest and easiest achievable devices could
      replace a specific aspect of renal function, such as an implantable device to
      produce erythropoietin. Both a bioartificial hemofilter and a renal tubule device
      may be developed. Ultimately this work may result in an implantable bioartificial
      kidney.

PMID- 9241723
TI  - Optimizing disease management in the next 25 years.
AB  - The concept of disease management will be increasingly applied to the chronic
      renal disease area in next quarter century. This concept emphasizes the
      management of the continuum of disease focusing rather than processing on
      episodes of illness. Primary and secondary disease prevention, avoidance of
      complications, improvement in health status, evidence-based selection of
      modalities of care, and rationalization of systems of care will have a profound
      effect on financing vehicles as well as the involvement of nephrologist and
      midlevel practitioners as providers of care.

PMID- 9241724
TI  - Progressive changes in cutaneous trigger zones for sensation referred to a
      phantom hand: a case report and review with implications for cortical
      reorganization.
AB  - The dominant model of cortical plasticity induced by peripheral denervation
      suggests that a physiologically-reorganized cortical area can acquire new
      perceptual meaning, including a change in the peripheral referral of sensation.
      An alternative view is that such an area may retain its former perceptual
      significance, even though it becomes responsive to new peripheral inputs. To
      examine evidence related to this issue, a clinical case is presented documenting
      the time course of changes in phantom limb sensation in a patient with accidental
      amputation of a hand. About 24 h after injury, a vivid phantom hand was present;
      tactile stimulation revealed cutaneous trigger zones on the arm, stimulation of
      which elicited sensation referred to specific fingers of the phantom. While the
      phantom hand percept remained fairly stable over time, the trigger zones expanded
      progressively in size during the next 1-8 weeks but had contracted and changed
      location considerably about one year later. At all times studied, the trigger
      zones were topographically related to specific fingers and other parts of the
      phantom hand. The implications of these and other recent clinical findings for
      cortical reorganization are discussed, and the following tentative conclusions
      are drawn. (1) A phantom percept is mediated by central neural networks which
      remain functionally intact after amputation. (2) Cutaneous trigger-zones mapped
      in humans correspond to novel receptive fields of cortical neurons mapped in
      animals following peripheral denervation. (3) Cortical reorganization induced by
      denervation does not produce a major change in perceptual meaning or peripheral
      reference. In the present case, stimulation of new trigger zones (receptive
      fields) on the patient's arm presumably activated a reorganized cortical hand
      area but evoked sensation still referred to the (now missing) hand. Hence,
      physiological cortical remapping is not necessarily accompanied by functional
      respecification.

PMID- 9241725
TI  - Localization of unmyelinated axons in rat skin and mucocutaneous tissue utilizing
      the isolectin GS-I-B4.
AB  - The alpha-D-galactose specific isolectin I-B4 from Griffonia simplicifolia (GS-I
      B4) labels CNS microglia and certain peripheral neurons, including a
      subpopulation of small dark, type B dorsal root ganglion cells, some post
      ganglionic sympathetic axons, and nearly all peripheral gustatory axons. The
      innervation patterns of GS-I-B4 reactive sensory ganglion cells are unknown for
      many peripheral target tissues, including their probable primary target, the
      skin. The present study describes the distribution of GS-I-B4 reactive axons in
      hairy and glabrous hindpaw skin and in the glans penis of rats, using both single
      and double-labelling histochemical techniques. Neuronal processes were identified
      using (1) histochemistry with horseradish peroxidase conjugated GS-I-B4 or (2)
      immunohistochemistry against PGP 9.5 to identify all axons, and biotinylated
      lectin histochemistry with avidin-FITC to identify the subpopulation of GS-I-B4
      reactive axons. GS-I-B4 strongly labelled unmyelinated cutaneous sensory
      afferents, as well as some sympathetic efferents and visceral afferents. lectin
      reactive axons were seen to innervate the upper hair shaft epidermis in hairy
      skin, and were abundant in the shallow dermis in hairy and glabrous skin and
      glans penis. Lectin reactive axons were also abundant in the lamina propria and
      distal urethral epithelium of the penis. These results provide new evidence for
      the cutaneous sensory role of GS-I-B4 reactive primary afferents, as well as
      evidence to support the contention that the lectin is a specific marker for a
      subpopulation of unmyelinated axons and not simply a marker for the myelination
      state of an axon.

PMID- 9241727
TI  - A survey of morphogenesis during the early postnatal period in PMBSF barrels of
      mouse SmI cortex with emphasis on barrel D4.
AB  - The long term goal of this work is to understand synaptogenesis in homologous
      regions of the cerebral cortex, i.e. a whisker barrel. Hemispheres of aldehyde
      perfused mice, at various ages from P6 to P65 (DOB = P0; three each), were
      osmicated and sectioned at 40 microns parallel to the pia. Barrels were
      identified, mapped and measured in sections through mid-level layer IV, and then
      embedded for electron microscopy. The main findings were: (1) Cell bodies and
      large diameter dendrites thin out in barrel hollows from P6 to P8. (2)
      Degeneration occurs primarily from P6 to P11, peaking on P8. (3) Single synapses
      from narrow, tubular axons predominate before P14; afterwards, multiple synapses
      from bag-like terminals increase in number. (4) The number of spines increases
      dramatically between P9 and P12. (5) Asymmetrical and symmetrical synapses occur
      at all ages studied; their junction lengths are not significantly different at
      any age. (6) Asymmetrical synapse density increases rapidly from P6 to P8, slowly
      from P9 to P.12, sharply between P13 and P14 along with patterned whisking,
      slowly to P20 and drops in adults. (7) Synapses onto spiny and non-spiny stellate
      cell bodies increase markedly from P10 to P20. (8) Changes in density of
      asymmetrical synapses in neuropil and of symmetrical synapses on spiny stellate
      cell bodies follow similar sequences but the sequence in neuropil is 72 h
      earlier. (9) When barrel size is taken into account, synaptogenesis is monotonic,
      increasing sharply in the second postnatal week followed by a slower increase
      into adulthood.

PMID- 9241728
TI  - The mole nose instructs the brain.
AB  - Star-nosed moles normally have 11 mobile appendages, or rays, extending from each
      side of the nose. In cytochrome oxidase preparations, each ray is visible in
      primary somatosensory cortex as a dark band separated by light septa. When a
      single mole was found with 12 rays on each side of the nose, primary
      somatosensory cortex had 12 bands. We take this as further evidence that
      morphological features of somatosensory cortex are determined by the periphery.

PMID- 9241726
TI  - Contributions of raphe-cortical and thalamocortical axons to the transient
      somatotopic pattern of serotonin immunoreactivity in rat cortex.
AB  - Two experiments were carried out to evaluate the relative contributions of
      thalamocortical and raphe-cortical fibers to the transient somatotopically
      organized pattern of serotonin (5-HT) immunoreactivity that appears in the
      primary somatosensory cortex (SI) of rats during the first 2 weeks of life. In
      the first experiment, the specific 5-HT uptake inhibitors, fluoxetine and
      paroxetine, were administered systemically, animals were killed 3, 6, or 12 h
      later, and cortices evaluated for 5-HT immunoreactivity. Fluoxetine treatment had
      no appreciable effect on the density of 5-HT immunoreactivity in the cortex.
      Paroxetine treatment caused a reduction in 5-HT immunoreactivity which was
      maximal 6 h after administration. Examination of the cortices of these animals
      revealed a loss of very fine dust-like 5-HT immunoreactivity, but a vibrissae
      related pattern remained visible in thicker fibers. In a second experiment, raphe
      cortical fibers were destroyed by systemic administration of 5,7
      dihydroxytryptamine on the day of birth. Six days after this manipulation, 5-HT
      was applied directly to the cortex in vivo and the animals were then killed and
      cortices processed to demonstrate 5-HT immunoreactivity. The cortices of these
      rats revealed a fine dust-like immunoreactivity organized in a somatotopic
      pattern, but only very few 5-HT-positive axons. The results of these experiments
      suggest that both raphe-cortical axons and thalamocortical fibers contribute to
      the patterned 5-HT immunoreactivity observed in SI of perinatal rats.

PMID- 9241729
TI  - Three dimensional structure of human fibrinogen under aqueous conditions
      visualized by atomic force microscopy.
AB  - Fibrinogen plays a central role in surface-induced thrombosis. However, the
      interactions of fibrinogen with different substrata remain poorly understood
      because of the difficulties involved in imaging globular proteins under aqueous
      conditions. We present detailed three dimensional molecular scale images of
      fibrinogen molecules on a hydrophobic surface under aqueous conditions obtained
      by atomic force microscopy. Hydrated fibrinogen monomers are visualized as
      overlapping ellipsoids; dimers and trimers have linear conformations
      predominantly, and increased affinity for the hydrophobic surface compared with
      monomeric fibrinogen. The results demonstrate the importance of hydration on
      protein structure and properties that affect surface-dependent interactions.

PMID- 9241730
TI  - Factor V Leiden, C > T MTHFR polymorphism and genetic susceptibility to
      preeclampsia.
AB  - We performed a case-controlled study to investigate whether the FV Leiden
      mutation and the C > T677 polymorphism of the 5, 10 methylene tetrahydrofolate
      reductase (MTHFR) are associated with the occurrence of preeclampsia in 96
      otherwise healthy preeclamptic women and 129 parous women as controls. FV Leiden
      carriers were 10 (10.5%) in cases and 3 (2.3%) in controls (OR: 4.9, 95% CI: 1.3
      18.3). MTHFR TT homozygotes were 28 (29.8%) in cases and 24 (18.6%) in the
      control group (OR: 1.8, 95% CI 1.0-3.5). No difference in any of the
      polymorphisms was found between proteinuric (n = 45) and non-proteinuric (n = 51)
      patients. Moreover, MTHFR polymorphism does not affect the association between FV
      Leiden and preeclampsia. In conclusion, FV Leiden mutation and MTHFR TT genotype
      are associated with the occurrence of preeclampsia, suggesting that, during
      pregnancy, women carrying these gene variants are prone to develop such a
      complication.

PMID- 9241731
TI  - Molecular and genetic analysis of two patients with Bernard-Soulier syndrome-
      identification of new mutations in glycoprotein Ib alpha gene.
AB  - We investigated two unrelated patients with Bernard-Soulier syndrome (BSS) by
      performing molecular and genetic analysis. A flow cytometric and immunoblotting
      analysis showed GP Ib alpha to be absent from the platelet membrane of both
      patients. Other glycoproteins that formed GP Ib/IX/V complex were present on the
      platelets, but in decreased amounts. Therefore, GP Ib alpha gene from both cases
      was sequenced after PCR amplification and subcloning. We identified a homozygous
      mutation of a dinucleotide deletion within the TGTG repeat at cDNA number 972 to
      975 in GP Ib alpha gene from Case 1. In Case 2, compound heterozygosity was
      demonstrated in GP Ib alpha gene; an insertion of a single base (T) at cDNA
      number 1,418 in one allele, and a deletion of a single base (A) within the 7
      adenine repeat at cDNA number 1,438 to 1,444 in another allele. The three new
      mutations in both patients appeared to cause a frameshift, which created a new
      termination codon shortly thereafter, and thus lead to a GP Ib alpha deficiency
      on the platelet membrane. Truncated mutant proteins could be detected in the
      plasma and platelets of Case 2, but not of Case 1. According to these findings,
      it is thus supposed that the properties and conformation of additional COOH
      terminal peptides, which were supposedly synthesized as results of the mutations,
      may have an important role on the processing of mutant GP Ib alpha in
      megakaryocytes and platelets.

PMID- 9241732
TI  - Factor XIII deficiency due to a Leu660Pro mutation in the factor XIII subunit-a
      gene in three unrelated Palestinian Arab families.
AB  - In this report we describe the molecular basis of FXIII a-subunit deficiency in
      three unrelated Palestinian Arab families. In three patients representing each
      family two substitutions were identified in exon 14 on both alleles: C to G
      change resulting in a Gln651Glu substitution (a previously described
      polymorphism) and a T to C transition causing Leu660Pro substitution. The latter
      is a new mutation which creates a restriction site for FnuDII enzyme. Restriction
      analysis performed in members of the three families clearly distinguished between
      severely affected patients, obligate carriers and unaffected subjects. A
      population survey failed to detect the mutation among 250 Jewish individuals but
      did detect two heterozygotes among 300 Arabs suggesting a 0.0033 frequency for
      the Pro660 allele in this population. In two out of the three families the Pro660
      allele was linked to allele 5 of the 5' short tandem repeat polymorphism within
      the FXIII a-subunit gene suggesting that the mutation might have occurred at
      least twice. cDNA obtained from mRNA isolated from patients' platelets and
      monocytes appeared similar in size to that of normal control indicating that the
      Leu660Pro mutation does not affect mRNA synthesis. Computer modeling based on
      cristallographic studies of the a-subunit of factor XIII predicted that the
      mutant protein is expected to misfold into a structure which is either unstable
      or susceptible to degradation.

PMID- 9241733
TI  - Molecular mechanisms of mutations in factor XIII A-subunit deficiency: in vitro
      expression in COS-cells demonstrates intracellular degradation of the mutant
      proteins.
AB  - Factor XIII deficiency is an autosomal recessive bleeding disorder that is
      largely caused by various mutations in FXIII A-subunit gene. Characteristically,
      the patients lack both A-subunit activity and antigen in the circulation. Here we
      have analysed the consequences of four missense mutations (Met242-->Thr, Arg252-
      >Ile, Arg326-->Gln, Leu498 to Pro) and one stop mutation (Arg661-->Stop) in the
      FXIII A-subunit gene by expression in COS-cells. After transient transfection
      each mutant cDNA expressed mRNA at an equal level to the wild type FXIII.
      However, the mutant polypeptides accumulated in the cells in significantly
      reduced quantities and demonstrated only very low enzymatic activity. Analysis of
      immunoprecipitated metabolically labelled polypeptides demonstrated remarkable
      instability and intracellular degradation of all mutant FXIII proteins. These
      results verify the deleterious nature of the individual amino acid changes and
      confirm that protein instability and susceptibility to proteolysis are
      consequences of the mutations, as predicted from the three-dimensional model of
      crystallised FXIII A-subunit.

PMID- 9241734
TI  - Leucocyte rheological properties are altered in patients with diffuse
      atherosclerosis.
AB  - To evaluate whether atherosclerosis may be associated with altered leucocyte
      rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means
      of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD
      44 (by means of immunofluorescence staining and flow cytometry) in 9 patients
      with carotid plus lower limb artery atherosclerosis (group A), 14 patients with
      carotid atherosclerosis only (group B) and 23 controls without atherosclerosis
      (group C). The level of LFA-1 (calculated as mean fluorescence channels-MFCs) on
      neutrophils, lymphocytes and monocytes was significantly higher (p < 0.05) in
      group A and B patients than in controls (group A-mean +/- SE: 383.77 +/- 9.42 vs
      295.45 +/- 5.76; 474.22 +/- 8.86 vs 388.35 +/- 7.84; 457.66 +/- 12.03 vs 396.25
      +/- 4.37. Group B: 322.42 +/- 6.36 vs 295.45 +/- 5.76; 421.42 +/- 7.21 vs 388.35
      +/- 7.84; 415.71 +/- 7.73 vs 396.25 +/- 4.37, respectively); furthermore, the MFC
      of LFA-1 on neutrophils was significantly different (p < 0.05) between group A
      and B patients. The percentage of aggregated leucocytes was significantly higher
      (p < 0.05) in group A patients (4.46 +/- 1.07) than those in groups B (1.75 +/-
      0.38) and C (1.43 +/- 0.25), whereas no significant difference was detected
      between groups B and C. Leucocyte number and expression of CD44 were not
      significantly different among the 3 groups. In conclusion, changes in leucocyte
      rheology are present in patients with atherosclerosis and may contribute to
      chronic ischaemia.

PMID- 9241735
TI  - Soluble P-selectin in atherosclerosis: a comparison with endothelial cell and
      platelet markers.
AB  - von Willebrand factor and soluble thrombomodulin are established plasma markers
      of endothelial cell dysfunction, whilst beta thromboglobulin is an established
      plasma marker of platelet activity. Soluble P-selectin may be the product of
      either or both types of cell and levels of all four molecules have been
      previously found to be increased in atherosclerosis. To determine the
      relationship of soluble P-selectin to the endothelial cell and platelet products,
      we measured the four indices in a case control study of 55 patients with
      peripheral vascular disease and 55 age and sex matched controls. von Willebrand
      factor (p < 0.0001), beta thromboglobulin (p = 0.0006), soluble P-selectin (p =
      0.0021) and soluble thrombomodulin (p = 0.021) were all raised in the patients.
      Soluble P-selectin correlated with beta thromboglobulin (r = 0.34, p = 0.019) but
      failed to correlate with either endothelial cell marker. Co-culture of
      endothelial cells in vitro with bovine thrombin resulted in increased levels of
      von Willebrand factor in the supernatants but levels of soluble thrombomodulin
      and soluble P-selectin were not enhanced. Exposure of endothelial cell monolayers
      to elastase resulted in different patterns of release of von Willebrand factor,
      soluble thrombomodulin and soluble P-selectin. We suggest that soluble P-selectin
      is unlikely to arise from the endothelium and may be a new marker of platelet
      activation in atherosclerosis.

PMID- 9241736
TI  - The origin of P-selectin as a circulating plasma protein.
AB  - P-selectin is a 140 kD protein found in the alpha-granules of platelets and the
      Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on
      the cell surface and also secreted into plasma. Whether the circulating soluble P
      selectin (sP-selectin) originates from platelets, endothelial cells, or both, is
      not known. We studied the level of sP-selectin in diseases with different
      platelet counts, with or without evidence of endothelial cell activation.
      Endothelial cell activation was confirmed by the detection of sE-selectin and ED1
      fibronectin. A significant positive correlation between platelet count and sP
      selectin concentration was observed in healthy controls, and in patients with
      thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n
      = 47; p < 0.001). In patients with idiopathic thrombocytopenic purpura (ITP) the
      sP-selectin concentration was 110 +/- 39 ng/ml (n = 10), compared to 122 +/- 38
      ng/ml in healthy controls (n = 26). However, their mean platelet count was lower
      (58 x 10(9)/l versus 241 x 10(9)/l in the control group). Accordingly, the levels
      of sP-selectin expressed per platelet increased to significantly higher levels
      (2.0 +/- 1.2 versus 0.6 +/- 0.2 fg/platelet in the control group; p < 0.0001).
      This suggests increased platelet turnover in patients with ITP. High levels of sP
      selectin were found in patients with sepsis (398 +/- 203 ng/ml; n = 15) and with
      thrombotic thrombocytopenic purpura (TTP; 436 +/- 162 ng/ml; n = 12). Compared
      with patients with ITP, the concentration of sP-selectin per platelet was higher
      in patients with sepsis (4.8 +/- 4.3 fg/platelet; p < 0.005) or TTP (17.1 +/- 9.5
      fg/platelet; p < 0.001). Endothelial cells are very likely to be the source in
      these patients and the presence of endothelial cell activation was confirmed by
      increased levels of circulating E-selectin and ED1-fibronectin. This study
      suggests that platelets are the major source of circulating sP-selectin in
      healthy individuals. Endothelial cell activation is associated with an increased
      sP-selectin concentration per platelet.

PMID- 9241737
TI  - Purpura fulminans induced by disseminated intravascular coagulation following
      infection in 2 unrelated children with double heterozygosity for factor V Leiden
      and protein S deficiency.
AB  - Purpura fulminans is associated with homozygous protein C and homozygous protein
      S deficiency or may follow bacterial or viral infections. We present 2 children
      from 2 unrelated Arab families with purpura fulminans who were double
      heterozygotes for factor V Leiden inherited from their fathers and protein S
      deficiency inherited from their mothers. No previous thrombotic events have
      occurred in either patient or their respective family members. In one patient
      sepsis accompanied by disseminated intravascular coagulation appeared to be the
      trigger of purpura fulminans. In the other patient varicella infection preceded
      purpura fulminans and was also associated with disseminated intravascular
      coagulation. This report emphasizes the need for evaluation of hereditary defects
      in the inhibitory mechanisms of blood coagulation in patients with purpura
      fulminans at any age.

PMID- 9241738
TI  - Plasminogen: an important hemostatic parameter in septic patients.
AB  - BACKGROUND: Previously we observed in some but not all septic patients a low
      plasma concentration of plasminogen. OBJECTIVES: To investigate prospectively
      whether plasma levels of plasminogen or the ratio of plasminogen to alpha-2
      antiplasmin have a prognostic value for survival from sepsis and to study the
      variation of other hemostatic parameters during septicemia. PATIENTS: The study
      population consisted of 45 consecutive patients with septicemia, 15 non-septic
      patients from the same intensive care unit and 30 healthy volunteers.
      MEASUREMENTS AND MAIN RESULTS: Plasminogen concentrations were significantly
      lower (p < 0.001) in plasma of septic patients (median 0,62 IU/ml range: 0.15
      1,06) than in plasma of healthy controls (median 1.00 IU/ml, range: 0.75-1.10) or
      of non-septic intensive care patients (median 1.00 IU/ml, range: 0.82-1.08).
      Among the other parameters tested, plasminogen activator inhibitor (PAI-1)
      antigen concentration and PAI activity were similar in septic and non-septic
      intensive care patients, but higher than in healthy controls. Concentrations of
      elastase-alpha-1-protease inhibitor or of thrombin-antithrombin complexes were
      higher in septic patients than in non-septic intensive care patients or healthy
      controls. A degraded form of plasminogen of 38 kDa was detected by Western blot
      analysis in the plasma of septic patients, but not in plasma of non-septic
      intensive care patients or controls. Plasminogen alone or the ratio of
      plasminogen to antiplasmin were good markers for survival from septicemia. E.g.
      for plasminogen at a cut off of 0.65 IU/ml, sensitivity was 90.5% and specificity
      66.7%, whereas for the ratio of plasminogen over antiplasmin at a cut off ratio
      of 0,65 IU/ml, sensitivity was 95.2% and specificity 70.8%. CONCLUSION:
      Plasminogen or the ratio of plasminogen to antiplasmin are sensitive markers for
      survival in patients with septicemia.

PMID- 9241739
TI  - Respective evaluation of the prevalence of haemostasis abnormalities in
      unexplained primary early recurrent miscarriages. The Nimes Obstetricians and
      Haematologists (NOHA) Study.
AB  - The prevalence of haemostasis abnormalities was evaluated in 500 consecutive
      women with unexplained primary recurrent miscarriages. Two matched reference
      groups with no antecedent of miscarriage were studied: 100 healthy mothers and 50
      childless women. In the prospective part of the study, we found 9.4% of the
      patients (95% C.I.: 6.8-12%) with an isolated factor XII deficiency, 7.4% of the
      patients (5.0-9.8%) with primary antiphopholipid antibodies, 47% of the patients
      (42.6-51.4%) with an insufficient response to the venous occlusion test and an
      isolated hypofibrinolysis was found in 42.6% (38.2-47%) of the patients
      (reference groups: respectively 0/150, 3/150, 2/150, p < 10(-3)). Willebrand
      disease, fibrinogen, deficiency, antithrombin, protein C or protein S
      deficiencies were not more frequent in recurrent aborters than in members of the
      reference groups. In the retrospective part of the study, cases of plasma
      resistance to activated protein C were not abnormally frequent. Patients had
      higher Willebrand factor antigen (vWF), tissue-type plasminogen activator antigen
      (t-PA), plasminogen activator inhibitor activity (PAI) and D-dimers (D-Di) than
      the reference women. Values of vWF, t-PA, PAI and D-Di were altogether correlated
      but were not related to C-reactive protein concentrations. Among patients, those
      with an antiphospholipid syndrome and those with an insufficient response to the
      venous occlusion test had higher vWF, t-PA, PAI and D-Di values than the patients
      with none of the haemostasis-related abnormalities. Thus, factor XII deficiency
      and hypofibrinolysis (mainly high PAI) are the most frequent haemostasis-related
      abnormalities found in unexplained primary recurrent aborters. In patients with
      antiphospholipid antibodies or hypofibrinolysis, there is a non-inflammatory
      ongoing chronic elevation of markers of endothelial stimulation associated with
      coagulation activation. This should allow to define subgroups of patients for
      future therapeutic trials.

PMID- 9241740
TI  - von Willebrand factor and factor VIII: C in acute cerebrovascular disease.
      Relationship to stroke subtype and mortality.
AB  - BACKGROUND: Elevated von Willebrand factor (vWF) is a risk factor in the
      development of acute myocardial infarction. The importance of vWF and factor
      VII:C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined.
      METHODS AND RESULTS: We studied 208 cases of stroke whose pathological type was
      defined by cranial computed tomography. Cerebral infarcts were grouped according
      to the Oxfordshire Community Stroke Project (OCSP) clinical classification. The
      results in patients were compared with 184 healthy reference subjects. In
      patients, vWF and FVIII:C levels were determined initially and after three
      months. Patients were followed prospectively for six months or until death.
      Levels of vWF and FVIII:C were elevated initially (1.86 IU/ml and 2.20 U/ml
      respectively) and after 3 months (1.51 IU/ml and 1.90 U/ml) compared with a
      healthy reference population (1.26 IU/ml and 1.49 U/ml p = 0.0001). In the
      initial sample, vWF was associated with age (p = 0.01). FVIII:C was related to
      age (p = 0.04), gender (p = 0.007 higher for females) and a history of diabetes
      mellitus (2.56 U/ml vs. 2.16 U/ml in non-diabetics, p = 0.008). Initial vWF
      levels were higher in subjects with large vessel disease (TACI/PACI) group
      compared with the small vessel disease (LACI) group [2.12 IU/ml, (n = 112) vs.
      1.48 IU/ml (n = 59) respectively, p = 0.0001] and similarly in initial FVIII:C
      levels (2.43 U/ml vs. 1.87 U/ml, p = 0.0001). Analysis of six-month case
      fatality, vWF levels were associated with risk of death [p = 0.01, OR 1.73 (1.12,
      2.66) for an increase of I U/ml], even after allowing for stroke type.
      CONCLUSION: The relationship of vWF with stroke mortality has not previously been
      described. Although we have not demonstrated a causal role for vWF in the
      pathogenesis of CVD, elevated circulating levels of vWF may be associated with
      increased risk of death following stroke. A prospective study would be required
      to establish whether vWF is predictive for the development of CVD.

PMID- 9241741
TI  - On the relationship between changes in the deep veins evaluated by duplex
      sonography and the postthrombotic syndrome 12 years after deep vein thrombosis.
AB  - In a prospective study we performed color duplex ultrasonography to evaluate
      patency and valvular function of previous thrombosed veins 12 years after the
      acute thrombosis. Normal clinical findings were found in 64% of the patients,
      mild postthrombotic skin changes in 28%, and marked trophic changes in 5%; only 1
      venous ulcer occurred. In 39 patients, 114 initially thrombosed vein segments
      were evaluated. Thirty-seven of 72 proximal segments were completely recanalized
      (23 with valvular incompetence) and 21 segments exhibited partial recanalization
      (19 with valvular incompetence). Superficial femoral vein segments were
      completely occluded in 19%, however, excellent collateralization was provided via
      the deep femoral vein. Thromboses of the posterior tibial vein demonstrated a
      high rate of recanalization with development of valvular incompetence in 52%.
      Whereas obstruction and valvular incompetence as single factors led to a
      postthrombotic leg in 8.5% and 33%, respectively, the most frequent cause for the
      development of the postthrombotic syndrome was the combination of reflux plus
      obstruction in the deep veins (50%). Compression therapy with elastic compression
      stockings is recommended for at least 5 years after the acute thrombosis.

PMID- 9241742
TI  - Multicenter retrospective study on the utilization of FEIBA in France in patients
      with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight
      Bypassing Activity.
AB  - Factor VIII or factor IX replacement is frequently impossible in inhibitor
      developing hemophiliacs, because of the level of the inhibitor titer. Activated
      prothrombin complex concentrates are one of the available options to treat the
      bleeding episodes in such patients. However, the efficacy of these products and
      the associated thrombogenic risk, particularly in prolonged administration such
      as employed during surgeries, are important concerns for hemophilia care
      providers. We performed a multicenter retrospective study to evaluate the use of
      FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433
      bleeding episodes, including surgical procedures, concerning 60 patients from 15
      hemophilia centers. The efficacy was judged as good or excellent in 352 episodes
      (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor
      and major surgical procedures were successfully performed using FEIBA as a second
      line therapy after human or porcine factor VIII, and in some occasions FEIBA was
      utilized as the only substitution product. The tolerance was assessed as good in
      428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3
      patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two
      of them the seroconversion occurred prior to the first use of FEIBA. In contrast,
      80.4% of the patients were HCV-seropositive. An anamnestic response after the
      administration of FEIBA was noted in 31.5% of cases. This study points out the
      main features of the use of FEIBA in France, and particularly the low HIV
      seroprevalence in the patients treated. The good efficacy and the excellent
      tolerance still confer to this product a place to consider in the therapeutic
      options for the treatment of inhibitor-developing hemophiliacs or in acquired
      hemophilia.

PMID- 9241743
TI  - Positive association of the beta fibrinogen H1/H2 gene variation to basal
      fibrinogen levels and to the increase in fibrinogen concentration during acute
      phase reaction but not to coronary artery disease and myocardial infarction.
AB  - BACKGROUND: Fibrinogen has been demonstrated to be an independent risk factor of
      cardiovascular disease. The absence of the HaeIII cutting site (H2 allele) of an
      H1/H2 gene variation in the promoter region of the beta fibrinogen gene was
      associated with increased levels of fibrinogen. METHODS AND RESULTS: In the
      present study, the effects of the H1/H2 gene variation not only on plasma
      fibrinogen concentrations but also on coronary artery disease (CAD) and
      myocardial infarction (MI) were investigated in 923 individuals who underwent
      coronary angiography for diagnostic purposes. Relation of the H1/H2 genotype to
      fibrinogen plasma levels: A strong association was observed between the H1/H2
      gene variation and fibrinogen levels. The differences in fibrinogen plasma levels
      between H2H2 and H1H1 homozygotes were almost threefold more pronounced within
      subjects with clinical chemical signs of an acute phase reaction (CRP > or = 7.5
      mg/l) than within a subgroup of subjects without these signs (CRP < 7.5 mg/l)
      (median of CRP distribution: 7.5 mg/l). In 207 patients who underwent
      aortocoronary bypass surgery plasma fibrinogen levels were almost identical
      directly after surgery. Two days after operation fibrinogen increased to clearly
      higher levels in H2H2 homozygotes than in H1H2 and H1H1 genotypes, whereas almost
      the same maximal increases in fibrinogen concentrations were reached 3-4 days
      after surgery in all individuals. Relation of the H1/H2 genotype to CAD and MI.
      Whereas in the total population the plasma fibrinogen concentrations were
      strongly associated with smoking, CAD and MI, an association of the H1/H2 gene
      variation to CAD and MI was not detected. However, mean age at first MI of H2H2
      individuals (62.9 years) was clearly higher than of H1H2 genotypes (56.9 years)
      and of H1H1 subjects (56.4 years). In addition, in a subgroup of individuals with
      a higher risk of MI by either high apoB and/or low apoA1 plasma levels the
      portion of MI patients was clearly smaller within H2H2 homozygotes than within
      H1H2 or H1H1 genotypes, although-also in these high risk groups-mean age at first
      MI of H2H2 individuals were higher than of the other two genotypes. CONCLUSIONS:
      Obviously, the H2 allele of the fibrinogen H1/H2 genotype does not only influence
      basal fibrinogen concentrations, but particularly also the extent of fibrinogen
      level increase during acute phase reaction. Whereas the fibrinogen plasma level
      is positively associated with coronary artery disease and myocardial infarction,
      the H2 allele-although exhibiting an association with elevated fibrinogen levels
      was not positively associated with CAD and MI.

PMID- 9241744
TI  - Habutobin splits the Arg16-Gly17 bond in the A alpha chain of rabbit fibrinogen.
AB  - We reported previously that habutobin, a thrombin-like enzyme from Trimeresurus
      flavoviridis venom, clotted only rabbit fibrinogen, whereas human, monkey,
      bovine, dog, rat and guinea-pig fibrinogens were unaffected. In the present
      study, we investigated the cleavage site of the rabbit A alpha chain by
      habutobin. The fibrinopeptide released by habutobin was identical to the
      fibrinopeptide A released by thrombin, and its amino acid sequence corresponded
      to A alpha 1-16 of rabbit fibrinogen. It was clarified therefore that habutobin
      cleaves the Arg16-Gly17 bond in the A alpha chain of rabbit fibrinogen.

PMID- 9241745
TI  - Tissue factor expression during monocyte-macrophage differentiation.
AB  - Tissue factor (TF), the high affinity receptor and cofactor of factor VII, is
      considered as the main procoagulant in stimulated monocytes and macrophages. We
      studied the effect of longterm culture (differentiation) on "spontaneous" and
      induced (LPS) expression of TF (mRNA, antigen, cell surface associated VIIa
      cofactor activity) in isolated human monocytes. TF was expressed transiently in
      monocytes cultured on Teflon membranes (suspension monocytes, Mo-S) and on
      plastic dishes (adherent monocytes, Mo-A), reaching maximal levels between days 3
      and 5. Increased expression of TF was accompanied by increased stable expression
      of macrophage specific markers (CD71, the mannose receptor, the scavenger
      receptor). Bacterial lipopolysaccharide (LPS) induced (additional) TF mRNA,
      antigen, and activity in both Mo-S and Mo-A. In Mo-S and Mo-A of days 3 to 5, the
      period in which there was "spontaneous" expression of TF, TF response to LPS was
      considerably lower. It is concluded that during monocyte-macrophage transition,
      TF is "spontaneously" and transiently expressed and that with respect to TF
      induction the responsiveness of the cells to LPS is maintained.

PMID- 9241746
TI  - Transient interruption of arterial thrombosis by inhibition of factor Xa results
      in long-term antithrombotic effects in baboons.
AB  - Recombinant tick anticoagulant peptide (r-TAP) is a potent and specific inhibitor
      of activated coagulation factor X which effectively interrupts in vivo arterial
      thrombosis during treatment. It is, however, uncertain if it also affects
      thrombosis after treatment is stopped. This was tested in a baboon model of
      arterial thrombosis where platelet deposition onto Dacron vascular graft
      segments, inserted as extensions into permanent femoral arteriovenous shunts, was
      measured. The baboons were intravenously treated with 10 micrograms/kg/min (low
      dose, aPTT = 39 +/- 1 s) and 25 micrograms/kg/min (high dose, aPTT = 58 +/- 2 s)
      r-TAP for two hours. During treatment the r-TAP inhibited thrombin formation and
      dose-dependently interrupted platelet deposition onto the graft segment. This
      effect lasted for up to two hours after treatment with the low dose. Following
      treatment with the high dose, the graft segments were kept in place for 53 h.
      After treatment was stopped, platelets again deposited, but at a much lower rate
      than in control studies. Maximum deposition was approximately 38% lower than in
      the control studies. Total platelet deposition over 55 h, calculated as the area
      under the deposition curve, was approximately 40% (p < 0.05) less than in the
      control studies. A significant shortening in the mean platelet life span and an
      approximately 15-fold increase in thrombin-antithrombin III complexes during the
      first 31 h indicated that the thrombus surface remained thrombogenic and that the
      effect of r-TAP was transient. We have shown that 2 h of treatment with a full
      antithrombotic dose of r-TAP markedly reduced both the rate of platelet
      deposition after treatment was stopped and the total number of platelets
      deposited over 55 h. This was in spite of the finding that the antithrombotic
      effect of r-TAP was transient.

PMID- 9241748
TI  - The anticoagulant and hemorrhagic effects of DHG, a new depolymerized holothurian
      glycosaminoglycan, on experimental hemodialysis in dogs.
AB  - We studied the use of depolymerized holothurian glycosaminoglycan (DHG) as an
      anticoagulant in experimental beagle-dog hemodialysis using a hollow-fiber
      dialyzer compared to that using unfractionated heparin (UFH), low-molecular
      weight heparin (LMWH), and nafamostat mesilate (FUT). Effectiveness was based on
      5 h hemodialysis and no marked clot deposition in the extracorporeal circuit. At
      effective doses, UFH and LMWH significantly prolonged template bleeding time, in
      sharp contrast to FUT and DHG, which scarcely prolonged bleeding time during
      hemodialysis. DHG prolonged activated partial thromboplastin time (APTT) about 6
      times that of normal plasma and prolonged thrombin clotting time (TCT) markedly;
      FUT showed marked APTT prolongation but hardly prolonged TCT in the hemodialysis
      circuit at the effective dose. The anticoagulant profile of DHG thus differs
      completely from that of FUT. These results suggest that DHG may be useful as
      anticoagulant for hemodialysis with low hemorrhagic risk.

PMID- 9241747
TI  - Relative efficacy of active site-blocked factors IXa, Xa in models of rabbit
      venous and arterio-venous thrombosis.
AB  - In order to investigate the respective roles of prothrombinase and intrinsic
      tenase (IXa/VIIIa) in venous thrombosis, we compared the anti-thrombotic efficacy
      of inhibitors of these two coagulation complexes. The agents tested were dansyl
      Glu-Gly-Arg chloromethyl ketone-inactivated bovine factor IXa(IXai) and Glu-Gly
      Arg chloromethyl ketone-inactivated human factor Xa (Xai). In vitro formation of
      active complexes (prothrombinase or tenase) was inhibited by Xai and IXai
      resulting in IC50 values of 3 nM and 5 nM, respectively. Antithrombotic activity
      was measured by inhibition of clot accretion on cotton threads placed in the
      abdominal vena cava of anesthetized rabbits. Intravenous bolus dosing followed by
      infusion of Xai during the experimental protocol resulted in a dose dependent
      reduction of clot weight, a dosage of 16.0 micrograms/kg + 0.28 microgram/kg/min
      being sufficient to produce a 96% inhibition of thrombosis. A much higher dose of
      IXai (1.0 mg/kg + 17.3 micrograms/kg/min) resulted in a 39% reduction of clot
      weight. In a rabbit arterio-venous shunt model mimicking arterial thrombosis, the
      relative efficacy of the two agents was found to be more comparable. The doses
      required for optimum antithrombotic activity were 128.0 micrograms/kg + 2.2
      micrograms/kg/min for Xai and 1.0 mg/kg + 17.3 micrograms/kg/min for IXai. We
      conclude that, in this study, prothrombinase rather than tenase inhibition was
      more effective in reducing venous thrombosis and that these effects can be
      achieved without disruption of extravascular hemostasis.

PMID- 9241749
TI  - A hemi-nested, allele specific, whole blood PCR assay for the detection of the
      factor V Leiden mutation.
AB  - We describe a novel hemi-nested, allele specific whole blood PCR assay for
      detection of the factor V Leiden mutation associated with the plasma defect,
      activated protein C resistance. This assay utilizes 5 microliters of whole blood
      without prior DNA extraction. The hemi-nested design, employing an outer primer
      pair in combination with nested, allele specific primers obviates the need for
      restriction enzyme digestion. PCR reactions are analysed directly on agarose or
      polyacrylamide minigels. The assay confirmed the genotypes of 50 individuals
      previously categorized by PCR and Mn11 digestion, and has been subsequently
      utilized in the genotyping of 445 individuals referred for thrombosis studies.

PMID- 9241750
TI  - The effect of N-linked glycosylation on molecular weight, thrombin cleavage, and
      functional activity of human protein S.
AB  - Human protein S (HPS) has three potential N-linked glycosylation sites at Asn458,
      468, 489. To study the role of glycosylation at these sites, PCR mutagenesis was
      used to abolish the consensus sequence of each N-linked glycosylation site
      (Asn458-->Gln, Ser460-->Gly; Asn468-->Gln, Thr470-->Gly; Asn489-->Gln, Thr491-
      >Gly) in full-length HPS cDNA. Each resulting construct was expressed in human
      kidney 293 cells by stable transfection of cDNA/SV40/adeno/pBR322-derived
      expression vectors, and conditioned medium was collected for recombinant protein
      purification. SDS-PAGE gels revealed that glycosylation mutants migrate
      identically and faster than the wild-type rHPS, showing that each of the three
      potential N-glycosylation sites contain a similar amount of carbohydrate. Mass
      spectral analysis yielded similar results and a molecular mass of approximately
      78,000 for wild-type HPS. To demonstrate that the difference in mobility between
      wild-type and mutant protein S is due to their carbohydrate content, plasma
      derived HPS and recombinant HPS were subjected to N-glycanase digestion and
      subsequently shown to migrate identically on SDS-PAGE gels. All forms of HPS have
      similar time courses for cleavage by alpha-thrombin. Functional studies indicate
      that wild-type rHPS possesses the same cofactor specific activity as plasma
      derived HPS, as tested by a standard clotting assay. Asn458 and Ser460 mutant
      rHPS have only a slightly higher cofactor activity, whereas the other four
      mutants have similar clotting activities, compared to wild-type rHPS. In a
      purified component system, glycosylation mutants of protein S showed a slightly
      enhanced ability to stimulate APC-mediated factor Va inactivation after an
      initial lag phase. The interaction of rHPS glycosylation mutants with human C4b
      binding protein (C4bp) was also studied by solution phase equilibrium binding
      assay. Two mutants (Asn458, Ser480) have marginally lower dissociated constants
      (Kd) with C4bp, whereas the others have the same apparent Kd as wild-type rHPS.

PMID- 9241751
TI  - Effects of heparin therapy on fibrinolysis in patients with pulmonary embolism.
AB  - Previous investigations suggested that heparin administration to humans enhances
      the tissue type plasminogen activator (tPA) levels in blood, but it remains
      uncertain whether this effect induces fibrinolysis. We studied the effect of
      therapeutic levels of heparinization on plasma markers for fibrinolysis in
      patients suspected of pulmonary embolism (PE). Blood samples were taken from 49
      consecutive patients; 28 had confirmed PE, 21 had PE excluded. On admission, the
      plasma levels of plasmin-alpha 2antiplasmin complexes and D-dimer were
      significantly higher in the patient group with PE compared to those in whom PE
      was excluded. After heparinization the tPA levels increased in both groups,
      showing that this effect was not dependent on the initial level of activity of
      fibrinolysis. In spite of this increment in tPA levels, the concentrations of
      plasmin-alpha 2antiplasmin complexes and D-dimer decreased. In conclusion,
      although heparinization in patients with or without pulmonary embolism does lead
      to elevated tPA:Ag levels, this is not accompanied by enhanced fibrinolysis.

PMID- 9241752
TI  - Regulation, location and activity of plasminogen activator inhibitor 2 (PAI-2) in
      peripheral blood monocytes, macrophages and foam cells.
AB  - Monocytes, macrophages and foam cells are central to atherogenesis. We have
      examined the potential ability of monocytes, macrophages and foam cells to affect
      the stability of deposited fibrin, characteristic of the atherosclerotic plaque,
      by their production of plasminogen activators and their inhibitors. Monocytes
      respond to thrombin and LPS by up-regulation of PAI-2 synthesis, and PAI-2 is
      their major product among the plasminogen activators/inhibitors. In contrast,
      macrophages and foam cells, while they did produce PAI-2, did not respond to
      thrombin and LPS by an increase in its synthesis. All PAI-2 produced by
      macrophages and foam cells was accumulated intracellularly, whereas monocytes
      also secreted PAI-2. Secreted PAI-2 was active as an inhibitor of u-PA, whereas
      intracellular PAI-2 required detergent treatment to generate activity. Thus
      monocytes, but not macrophages or foam cells, produce and secrete active PAI-2,
      thus potentially affecting fibrin stability in the local environment.

PMID- 9241753
TI  - Streptokinase entrapment in interdigitation-fusion liposomes improves
      thrombolysis in an experimental rabbit model.
AB  - The successful design of new thrombolytic agents depends on providing these
      agents with increased clot selectivity. As recently demonstrated (10), entrapment
      of tissue plasminogen activator into liposomes apparently provided the selective
      targeting needed to improve the efficacy of this fibrinolytic agent. To test
      whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent
      with a different mode of action and inactivation, we compared liposomal
      streptokinase with free streptokinase in an experimental rabbit model of
      thrombolysis. First we adapted a new method to produce liposomes of high
      entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the
      encapsulation of streptokinase. This system was then tested in an in vivo rabbit
      model of thrombolysis where animals with established clots were infused with
      either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase,
      free streptokinase+empty liposomes, or the corresponding amount of empty
      liposomes or saline. Significant differences (p < 0.05) in the percent clot lysis
      were observed between saline control (22.4 +/- 3.3%; mean +/- S.E.), free
      streptokinase (36.3 +/- 3.4%), and liposomal streptokinase (47.4 +/- 1.4%).
      Importantly, animals treated with empty liposomes experienced a level of
      thrombolysis (32.4 +/- 2.8%) not different to that produced by free streptokinase
      or empty liposomes plus free streptokinase (38.0 +/- 2.0%). We believe the effect
      of liposomes alone is due to a transient redistribution or margination of
      circulating platelets. When tested in rabbits immunized against streptokinase,
      liposomal (33.8 +/- 1.5%) but not free streptokinase (29.3 +/- 2.1%) showed
      significant thrombolytic activity compared to saline (22.4 +/- 3.3%) (p < 0.05).
      The thrombolytic activity was comparable to free streptokinase in non-immunized
      rabbits. This suggests liposomal streptokinase would have better thrombolytic
      activity than streptokinase alone and still provide to those patients possessing
      high levels of anti-streptokinase antibodies (5% of the population) the
      equivalent degree of therapy expected from free streptokinase.

PMID- 9241754
TI  - The Leu33/Pro polymorphism (PlA1/PlA2) of the glycoprotein IIIa (GPIIIa) receptor
      is not related to myocardial infarction in the ECTIM Study. Etude Cas-Temoins de
      l'Infarctus du Myocarde.
AB  - The GPIIb/IIIa receptor complex may contribute to acute coronary syndromes by
      mediating platelet aggregation. The Leu33/Pro polymorphism (PlA1/PlA2) of the
      GPIIIa has recently been shown to be associated with CHD in a small case-control
      study. We have investigated this polymorphism in a large multicenter study of
      patients with myocardial infarction and controls and found no difference in the
      distribution of allele and genotype frequencies between cases and controls.

PMID- 9241755
TI  - Epinephrine induces von Willebrand factor release from cultured endothelial
      cells: involvement of cyclic AMP-dependent signalling in exocytosis.
AB  - von Willebrand factor (vWf) is released from endothelial cell storage granules
      after stimulation with thrombin, histamine and several other agents that induce
      an increase in cytosolic free calcium ([Ca2+]i). In vivo, epinephrine and the
      vasopressin analog DDAVP increase vWf plasma levels, although they are thought
      not to induce vWf release from endothelial cells in vitro. Since these agents act
      via a cAMP-dependent pathway in responsive cells, we examined the role of cAMP in
      vWf secretion from cultured human umbilical vein endothelial cells. vWf release
      increased by 50% in response to forskolin, which activates adenylate cyclase. The
      response to forskolin was much stronger when cAMP degradation was blocked with
      IBMX, an inhibitor of phosphodiesterases (+200%), whereas IBMX alone had no
      effect. vWf release could also be induced by the cAMP analogs dibutyryl-cAMP
      (+40%) and 8-bromo-cAMP (+25%); although their effect was weak, they clearly
      potentiated the response to thrombin. Epinephrine (together with IBMX) caused a
      small, dose-dependent increase in vWf release, maximal at 10(-6) M (+50%), and
      also potentiated the response to thrombin. This effect is mediated by adenylate
      cyclase-coupled beta-adrenergic receptors, since it is inhibited by propranolol
      and mimicked by isoproterenol. In contrast to thrombin, neither forskolin nor
      epinephrine caused an increase in [Ca2+]i as measured by fura-2 fluorescence. In
      addition, the effects of forskolin and thrombin were additive, suggesting that
      they act through distinct signaling pathways. We found a close correlation
      between cellular cAMP content and vWf release after stimulation with epinephrine
      and forskolin. These results demonstrate that cAMP-dependent signaling events are
      involved in the control of exocytosis from endothelial cells (an effect not
      mediated by an increase in [Ca2+]i) and provide an explanation for epinephrine
      induced vWf release.

PMID- 9241756
TI  - Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA
      expression without changing that of tissue type plasminogen activator or tissue
      factor pathway inhibitor in cultured rat aortic endothelial cells.
AB  - Angiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent
      the recurrence of cardiovascular events. The mechanism of this decrease, however,
      can not be completely explained by anti-hypertensive and anti-hypertrophic
      effects of ACE-I. To investigate the mechanism of this decrease, we studied the
      regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen
      activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI)
      by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II
      increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI.
      These inductions were accompanied by increases in PAI-1 and TF activities and
      were inhibited by a type I Ang II receptor antagonist. The results suggest that
      Ang II decreases the antithrombotic properties of endothelial cells which
      increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin
      system may be beneficial to prevent thrombus formation in treatment of ischemic
      heart disease.

PMID- 9241757
TI  - Inhibition of thrombin-mediated cellular effects by triabin, a highly potent
      anion-binding exosite thrombin inhibitor.
AB  - Triabin, a 17 kDa protein from the saliva of the assassin bug Triatoma
      pallidipennis is a potent thrombin inhibitor interfering with the anion-binding
      exosite of the enzyme. The recombinant protein, produced by the
      baculovirus/insect cell system, was used to study the inhibitory effect on
      thrombin-mediated cellular responses. The thrombin (1 nM)-stimulated aggregation
      of washed human platelets and the rise in cytoplasmic calcium in platelets were
      inhibited by triabin at nanomolar concentrations. In contrast, the rise in
      calcium induced by the thrombin receptor-activating peptide (10 microM) was not
      suppressed by triabin. In isolated porcine pulmonary arteries, preconstricted
      with PGF 2 alpha thrombin (2 nM) elicited an endothelium-dependent relaxation
      which was inhibited by triabin in the same concentration range as found for the
      inhibition of platelet aggregation. Higher concentrations of triabin were
      required to diminish the contractile response of endotheliumdenuded pulmonary
      vessels to thrombin (10 nM). In cultured bovine coronary smooth muscle cells, the
      mitogenic activity of thrombin (3 nM), measured by [3H]thymidine incorporation,
      was also suppressed by triabin. In all these assays, the inhibitory effect of
      triabin was dependent on the thrombin concentration used. These studies suggest
      that the new anion-binding exosite thrombin inhibitor triabin is one of the most
      potent inhibitors of thrombin-mediated cellular effects.

PMID- 9241758
TI  - Protein S deficiency: a database of mutations. For the Plasma Coagulation
      Inhibitors Subcommittee of the Scientific and Standardization Committee of the
      International Society on Thrombosis and Haemostasis.

PMID- 9241759
TI  - Thrombolytic therapy in pediatric patients.

PMID- 9241760
TI  - Potential misdiagnosis of factor V Leiden: a comparison of two genotyping
      techniques.

PMID- 9241761
TI  - Normal prevalence of factor V Leiden gene mutation in patients with severe
      unstable angina.

PMID- 9241762
TI  - Relative risk of pulmonary embolism and deep vein thrombosis in association with
      the factor V Leiden mutation in a United Kingdom population.

PMID- 9241763
TI  - Abnormal histograms of platelets and spuriously normalizing platelet counts by
      Sysmex cell counters in hemolytic uremic syndrome due to Escherichia coli O157:H7
      infection.

PMID- 9241764
TI  - Soluble P-selectin, thrombocytopenia and von Willebrand factor in HIV infected
      patients.

PMID- 9241766
TI  - Activated protein C concentrate: a new tool for the treatment of acute
      thromboembolism in patients with congenital protein C deficiency.

PMID- 9241765
TI  - Severe bleeding due to factor V inhibitor after repeated operations using fibrin
      sealant containing bovine thrombin.

PMID- 9241767
TI  - The differences in the expression of CD45 isoforms on peripheral blood
      lymphocytes derived from patients with seasonal or perennial atopic allergy.
AB  - In order to determine the role of memory/naive T cells in atopic allergy patients
      we analyzed peripheral blood mononuclear cells before and during the grass pollen
      season. The study comprised 28 patients with seasonal symptoms of atopic allergy
      and 18 with perennial symptoms. Flow cytometry was employed to detect the
      expression of CD3, CD4, CD4CD45RA, CD4CD45RO, CD8, CD16, and CD19 molecules on
      peripheral blood lymphocytes. Allergic patients showed a decreased proportion of
      memory (CD4+CD45RO+) T cells compared with healthy subject (p < 0.05). The
      proportion of naive (CD4+CD45RA+) helper T cells did not differ between allergic
      patients and controls. The percentage of CD4+CD45RO+ cells increased during
      natural antigen exposure (grass pollen season) in allergic patients with seasonal
      symptoms. The results show at least two important observations. A potential
      homing tendency to nasal, bronchial and conjunctival mucosa of memory T cells
      (CD45RO) in atopic allergy patients may explain their deficiency in peripheral
      blood. Secondly, the grass pollen season may switch their phenotype from naive
      into memory T cells causing the increase of CD45RO cells. These events do not
      occur in non-allergic individuals and may thus constitute new insight into the
      basic mechanism of atopic allergy.

PMID- 9241768
TI  - Striate cortical generators of the N75, P100 and N145 components localized by
      pattern reversal visual evoked magnetic fields.
AB  - Magnetic fields evoked by checkerboard pattern reversal visual stimulation to the
      monocular left or right half-field were recorded over the whole head using a
      helmet-shaped 64 channel magnetoencephalography system in fourteen normal
      subjects. The sources of the triphasic N75m-P100m-N145m responses were located
      using a single current dipole model. Relative locations and orientations of the
      N75m and N145m dipoles to the P100m dipole were calculated for each subject to
      reduce errors due to 'anatomical variability and then averaged for all subjects
      under the same stimulus conditions. These averaged parameters showed that N75m
      and N145m originated from the same location in the striate cortex as P100m and
      reversed their orientations successively by 180 degrees during the time course.

PMID- 9241769
TI  - Evidence of alpha-helix slidings during bacteriorhodopsin photocycle-energetics
      coupling.
AB  - The three-dimensional structure of bacteriorhodopsin indicates that the all-trans
      cis retinal bending causes alpha-helix slidings during the bacteriorhodopsin
      photocycle. For the elucidation of alpha-helix slidings taking place during the
      bacteriorhodopsin photocycle, we calculated ASAs of hydrophobic and hydrophilic
      atoms translocated by alpha-helix slidings with thermodynamic criteria found
      previously. Thermodynamic parameters calculated from ASAs (calculated delta
      Gtransfer and T delta S) were consistent with those (observed delta Gtransfer and
      T delta S) obtained empirically. These findings indicate that alpha-helix
      slidings take place during bacteriorhodopsin photocycle-energetics coupling.
      These mechanisms not only explain various phenomena, including some mutants
      forming a long-lived intermediate, but also predict various yet-unobserved
      phenomena, including the generation of heat in early photocycle intermediates.

PMID- 9241770
TI  - Tetralogy of Fallot with absent pulmonary valve: evaluation with magnetic
      resonance imaging.
AB  - Two infants with tetralogy of Fallot with absent pulmonary valve were studied
      with electrocardiographically gated magnetic resonance imaging using a 1.5 T
      imaging system. In each case, imaging was performed successfully. The magnetic
      resonance imaging clearly demonstrated a rudimentary pulmonary valve, an
      aneurysmal pulmonary artery, and compression of the mainstem bronchi. Cine MRI
      revealed phasic compression of the bronchi by an aneurysmally dilated pulmonary
      artery. Magnetic resonance imaging produced high quality images and provided all
      of the anatomic information required for preoperative evaluation.

PMID- 9241771
TI  - Nutritional evaluation of women in urban areas in continental China.
AB  - In 1993-1995, a nutritional survey was conducted in China, in which 50 women each
      in three cities of Beijing, Shanghai and Nanning (thus 150 in total) volunteered
      to offer 24-hr total food duplicates and peripheral blood samples. People daily
      took 1,776 kcal (7,431 kJ) energy, 57 g protein, 75 g lipid, 218 g carbohydrate,
      439 mg calcium, 24 mg iron, 3,398 mg sodium and 1,521 mg potassium. When compared
      with the recommended dietary allowance for Chinese, intakes of energy, iron and
      possibly vitamin C were sufficient in a majority of the participants, but not so
      in cases of calcium, and several vitamins. The lipid energy ratio was 38% on an
      average and was higher than 30% in a majority (73%) of the people. BMI, but not
      the lipid energy ratio, correlated with the serum triglyceride level. In
      accordance with high iron intake, the prevalence of anemia was low. Inter-city
      differences were evident in nutrient sources. Thus, Beijing people took more
      amounts of protein and lipid from meats (including eggs and milk), whereas plant
      based foods were important sources of lipid in Shanghai and that of protein in
      Nanning. Furthermore, consumption of rice was significantly lower in Beijing than
      in Shanghai and Nanning, whereas wheat consumption was higher in Beijing than in
      Shanghai and Nanning.

PMID- 9241772
TI  - Changes in nitric oxide generated by the oxidation of oxymyoglobin by nitrite.
AB  - We found that nitric oxide (NO) was produced during the oxidation of oxymyoglobin
      by nitrite, by using a NO-selective electrode system, which enabled us to measure
      NO in phosphate solution, continuously and quantitatively. When 500 microM
      nitrite was added in the solution of oxymyoglobin (65 microM in heme),
      oxymyoglobin was oxidized to metmyoglobin in a sigmoidal manner. During the
      reaction, NO was generated quickly at the initial lag phase, and reached its peak
      (NO approximated to 30 microM), before the burst oxidation of oxymyoglobin
      occurred. Then, NO content was gradually decreased. By the addition of the
      increased concentration of nitrite (1 mM or 2 mM) to oxymyoglobin solution (65
      microM in heme), the production rate of NO was much accelerated and the amounts
      of NO were increased, in good accordance with the accelerated oxidation of
      oxymyoglobin by nitrite. These results suggest that NO is involved in the
      oxidation of oxymyoglobin by nitrite.

PMID- 9241773
TI  - Hindquarter sympathetic tone induced by small blood loss in conscious rats.
AB  - We have designated the hindquarter (or terminal aortic) vascular resistance (HQR)
      of the rat as hindquarter compensator (HC) because it increases after such
      hypotensive interventions as pentobarbital anesthesia and nitrate administration,
      presumably due to reflex excitation of regional vasoconstrictor fibers. The aim
      of the present study was to observe whether the HC mechanism is also mobilized in
      response to hemorrhage. Rats were implanted with a 1.5 or 2 mm diameter
      electromagnetic flow probe at the terminal aorta for measurement of hindquarter
      flow (HQF). An indwelling catheter was placed in the right common carotid artery
      to measure arterial pressure (AP) and withdraw blood. Experiments were performed
      in conscious rats two or three days after implantation. HQR was calculated by
      dividing AP by HQF. About 10 min after withdrawing blood (0.3 ml/100 g body
      weight), ganglionic blockade with hexamethonium bromide significantly decreased
      HQR, which indicated a mobilization of the HC mechanism, a change not observed
      with superior mesenteric resistance. A quantitatively similar change was observed
      in HQR after withdrawing double the amount of blood, i.e., 0.6 ml/100 g body
      weight, suggesting that the HC mechanism is activated almost fully by the
      relatively small amount of blood loss of 0.3 ml/100 g body weight.

PMID- 9241774
TI  - Characterization of human amniotic epithelial cells transformed with origin
      defective SV40 T-antigen gene.
AB  - This paper describes characteristics of human amniotic epithelial cells (AEC)
      transfected with a gene of origin-defective simian virus (SV) 40 large T-antigen
      (pMTIOD). Normal AEC before transfection with pMTIOD exhibited only low
      proliferative potential under our culture conditions. On the other hand, AEC
      cells transfected with pMTIOD exhibited greater proliferative potentials. Flow
      cytometry and immunohistochemistry analyses showed that both the primary and the
      transfected AEC did not express appreciable levels of class II antigens. However,
      the expression of class I antigen of the transfected AEC cells was slightly
      increased. The cells obtained in this experiment have the ability to induce
      tumors in severely combined immunodeficiency mice. This finding suggests that
      established AEC line can be used as a tool to investigate possible expression of
      the desired gene in human AEC and the gene products, however, was not suitable as
      a gene carrier to the recipient. Further experiments will be required to
      establish AEC as a transgene carrier for somatic cell gene therapy.

PMID- 9241775
TI  - Different grades of medial hypertrophy and intimal changes in small pulmonary
      arteries among various types of congenital heart disease with pulmonary
      hypertension.
AB  - Morphometric analysis of small pulmonary arterial changes was performed in three
      patients with different congenital heart disease with pulmonary hypertension:
      congenital mitral stenosis (MS), ventricular septal defect (VSD) and
      transposition of the great arteries (TGA). The material was biopsy or autopsy
      lung specimens, all having the same degree of elevated pulmonary arterial
      pressure. Medial thickness was determined by the method of Suwa and Takahashi,
      and the degree of intimal changes was quantified using the index of pulmonary
      vascular disease (IPVD) by Yamaki and Tezuka. It was demonstrated that the medial
      thickening of the small pulmonary arteries was the strongest in the patient with
      congenital MS, moderate in VSD, and the weakest in TGA, with statistically
      significant differences between each pair of these three conditions.
      Interestingly, the order of severity for intimal changes was reversed: it was the
      severest in TGA and the mildest in congenital MS. We surmise that in patients
      with TGA, medial hypertrophy is suppressed by sustained vasodilation resulting
      from the high oxygen saturation of pulmonary arterial blood, while in congenital
      MS, the media undergoes the severest hypertrophy because of the low oxygen
      saturation. We also conclude that in TGA intimal changes readily develop in the
      presence of attenuated media, while in congenital MS, the thickened media seems
      to prevent intimal changes. From a clinical viewpoint, these results urge us to
      recommend early surgical intervention in TGA and VSD where severe intimal changes
      can develop in the absence of extreme medial thickening. It may not be
      appropriate to extend operation on patients with congenital MS, since strongly
      thickened media can trigger vasospasms and medial necrosis.

PMID- 9241776
TI  - A case of nonpenetrating traumatic aortic regurgitation detected by
      transesophageal echocardiography.
AB  - A 67-year-old man, who had fell 5 meters, landing on his back, one month before,
      was referred because of heart failure due to aortic regurgitation (AR).
      Transesophageal echocardiogram (TEE) confirmed injuries in the aortic valve and
      the Valsalva sinus of the aorta before the surgery: the intimal flap in the
      Valsalva sinus of right coronary cusp (RCC), the prolapse of the RCC, and the
      dissection by longitudinal length of 3 cm in the Valsalva sinus of noncoronary
      cusp (NCC), ending as a blind pouch. Postoperative TEE confirmed the dissection
      was not repaired in the Valsalva sinus of the NCC. In this instance, TEE was
      extremely useful, compared with transthoracic echocardiography, computed
      tomography and magnetic resonance imaging, to assess the mechanism of AR
      following a nonpenetrating trauma, and to know to what degree the aortic valve
      and the Valsalva sinus of the aorta were destroyed.

PMID- 9241778
TI  - Intraarticular envenomation by Trimeresurus flavomaculatus mcgregori resulting in
      joint destruction.
AB  - This article reports a case of digital intraarticular envenomation from a T.
      flavomaculatus mcgregori pit viper resulting in severe joint damage. Bites by
      these snakes are rare in the U.S.A. since this species is only found in
      collections and zoos. Intraarticular envenomations from crotalids are rare and
      may result in joint destruction.

PMID- 9241777
TI  - Toxins and genes isolated from scorpions of the genus Tityus.
AB  - Scorpion venoms contain a variety of low mol. wt peptides toxic to different
      organisms. These peptides have been intensively studied because they represent
      excellent models for investigating structure-function relationships and they are
      also fine probes for studying ionic channel functions. This review deals with the
      biological and chemical aspects of toxic peptides that affect Na+ or K+ channels
      and the cloning of the cDNAs and genes encoding the main alpha and beta
      neurotoxins present in the venom of the three most dangerous species of Brazilian
      scorpion, Tityus bahiensis, Tityus stigmurus and Tityus serrulatus, and the
      Venezuelan scorpion Tityus discrepans. At least 16 different peptides specific
      for Na+ channels and five affecting K+ channels were isolated and characterized
      from the venom of these scorpions. The isolation of cDNAs and genes encoding four
      distinct toxins has permitted the elucidation of their nucleotide sequences as
      well as their genomic organization. Venoms and isolated toxins from scorpions of
      the genus Tityus were shown to enhance the secretory activity of the pancreas.
      Antisera obtained against venom of T. serrulatus show cross-reactivity with other
      species of the Brazilian scorpions.

PMID- 9241779
TI  - Okadaic acid and its interaction with sodium, potassium, magnesium and calcium
      ions: complex formation and transport across a liquid membrane.
AB  - Okadaic acid, a macrocyclic polyether compound, was shown to mediate the transfer
      of Na+, K+, Mg2+ and Ca2+ ions from aqueous solution to an organic phase, with a
      preference for Na+ ions. A kinetic study of the transport of these ions across a
      liquid membrane showed that the Na+ ion was more rapidly transported than the
      other ions and that the Na+ ion flux was dependent on the okadaic acid
      concentration.

PMID- 9241780
TI  - Inhibitory properties of the antibothropic complex from the South American
      opossum (Didelphis marsupialis) serum.
AB  - The South American opossum Didelphis marsupialis is known to be highly resistant
      to snake envenomation. In this paper it is shown that the opossum serum inhibits
      haemorrhage induced by both Crotalinae and Viperinae venoms. Tested against
      Bothrops jararaca (jararaca) venom, the antibothropic complex (ABC) isolated from
      the opossum serum was at least six times more antihaemorrhagic than the
      commercial antivenom. ABC showed no proteolytic activity by itself and was not
      hydrolysed by the venom. It inhibited the hydrolysis of casein by B. jararaca
      venom, but did not inhibit its hydrolytic activities upon N alpha-benzoyl-L
      arginine ethyl ester (BAEE) and N alpha-benzoyl-DL-arginine p-nitroanilide
      (BAPNA). The inhibitor did not interfere with trypsin and bacterial collagenase
      activities on BAPNA and N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala (FALGPA),
      respectively. It reduced chymotrypsin hydrolysis of N-acetyl-L-tyrosine ethyl
      ester (ATEE) because ABC is also a substrate for this enzyme. By sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, B. jararaca venom preferentially
      degraded fibrinogen A alpha-chain and fibrin alpha-chain. Tested on extracellular
      matrix proteins, the venom hydrolysed collagen IV, gelatins I and V, laminin and
      fibronectin, besides depolimerizing collagen I alpha-chain dimers. Fibrillar
      collagen V was not digested. These hydrolyses were inhibited by ABC and by EDTA.
      Our results show that the antibothropic complex is a venom metalloproteinase
      inhibitor, which could, at least partially, account for its antihaemorrhagic
      activity. Electrophoretic evidence indicated non-covalent complex formation
      between the antihaemorrhagic factor and component(s) of B. jararaca venom.

PMID- 9241781
TI  - Inhibition of the hemorrhagic activity of Bothrops asper venom by a novel
      neutralizing mixture.
AB  - This study screened 25 sera, 19 synthetic products and five antivenoms obtained
      after immunization for their ability to neutralize the hemorrhagic activity of
      venom from the snake Bothrops asper. Among the sera screened, the homologous
      serum of B. asper itself was found to possess the highest neutralizing capacity,
      abolishing the hemorrhagic effect of the venom at weight ratio of 3:1. It was
      more efficient than the antisera obtained by immunization. Among the synthetic
      compounds tested, only O-phenanthroline and EDTA salts inhibited the hemorrhagic
      activity at concentrations of 0.5-10 mM; however, only CaNa2EDTA was non-toxic at
      the concentrations studied. Intravenous injections and in situ administration of
      the non-toxic inhibitors revealed that a fraction of B. asper serum, the horse
      polyvalent antivenom and CaNa2EDTA were the most potent antihemorrhagic materials
      against B. asper venom, especially when administered in situ as a mixture. This
      work suggests that this neutralizing mixture could be highly useful in the
      neutralization of local and systemic hemorrhage developing after B. asper
      envenomation.

PMID- 9241782
TI  - Cloning and expression of a cysteine-rich venom protein from Trimeresurus
      mucrosquamatus (Taiwan habu).
AB  - A full-length cDNA for cysteine-rich venom protein (CRVP) was constructed by
      immunoscreening and 5'-rapid amplification of cDNA ends from a cDNA library of
      venom gland of Trimeresurus mucrosquamatus. The predicted CRVP consisted of 183
      amino acid residues including a putative signal peptide of 21 residues. Northern
      blot hybridization suggested the tissue-specific expression in venom gland and
      its corresponding length of cDNA. The predicted amino acid sequence of CRVP was
      homologous to a rat epididymal metalloprotein and a lizard helothermine. Amino
      acid sequence analysis suggested that CRVP may be a venom metalloprotein targeted
      against ryanodine receptors and Ca2+ release. Moreover, CRVP expressed in
      Escherichia coli exhibited the same antigenicity as their native venom forms of
      T. mucrosquamatus. This is the first report in the cloning and expression of a
      CRVP from the venom gland of T. mucrosquamatus.

PMID- 9241783
TI  - Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack
      (Caranx latus).
AB  - The toxins involved in ciguatera (fish poisoning) in the Caribbean Sea were
      isolated from Caranx latus, a pelagic fish often implicated in ciguatera in the
      Caribbean region, and purified by mouse bioassay directed fractionation. Five
      toxins were separated by reverse-phase high-performance liquid chromatography
      (HPLC). In order of increasing hydrophobicity, these toxins included a sleep
      inducing fraction (< 1% of total toxicity), a major Caribbean ciguatoxin (C-CTX
      1, 65% of toxicity), a minor Caribbean ciguatoxin (C-CTX-2, 13% of toxicity), a
      minor toxin (approximately 1% of toxicity) and a hydrophobic, fast-acting toxin
      (approximately 19% of toxicity). The i.p. injection into mice of each toxin
      induced signs typical of site-5 sodium channel activator toxins such as the
      Pacific ciguatoxins and brevetoxins. C-CTX-1 and C-CTX-2 were purified to
      homogeneity (LD50 = 3.6 and approximately 1 microgram/kg, respectively) and
      subjected to ion spray mass spectrometry. Both lost up to five H2O molecules and
      each had a [M+H]+ ion, m/z 1141.7, suggesting that C-CTX-1 and -2 are
      diastereomers that differ from the Pacific family of ciguatoxins. Turbo-assisted
      HPLC-mass spectrometry identified C-CTX-1, C-CTX-2 and three C-CTX-1-related
      compounds in an enriched fraction but no Pacific ciguatoxins were detected. The
      presence of different families of ciguatoxins in ciguateric fish from the
      Caribbean Sea and Pacific Ocean probably underlies the clinical differences in
      the ciguatera syndrome reported in these two regions. A Caribbean strain of the
      benthic dinoflagellate, Gambierdiscus toxicus, is suspected as source of these
      ciguatoxins. The extent to which these toxins are biotransformed as they pass
      through the marine food chain remains to be determined.

PMID- 9241784
TI  - Detection of an anatoxin-a(s)-like anticholinesterase in natural blooms and
      cultures of cyanobacteria/blue-green algae from Danish lakes and in the stomach
      contents of poisoned birds.
AB  - Ten natural bloom samples of cyanobacteria from the Danish lakes Knud so (5),
      Ravn so (4), and Salten Langso (1) collected during 1993-1995 were assayed for
      toxicity by mouse bioassay, for acetylcholinesterase inhibiting activity by a
      colorimetric method, and for microcystins by enzyme-linked immunosorbent assay.
      In the mouse bioassay, seven samples were neurotoxic, two were non-toxic and one
      gave a protracted toxic response. One of the non-toxic and the single protracted
      toxic sample both contained anticholinesterase activity equivalent to 4
      micrograms anatoxin-a(s) g-1. The neurotoxic samples contained equivalents to 20
      3300 micrograms anatoxin-a(s) g-1. The highest anticholinesterase activities
      (equivalent to 2300 and 3300 micrograms anatoxin-a(s) g-1, respectively) were
      found in samples collected from Lake Knud so in connection with bird-kills in
      1993 and 1994. Small amounts of microcystins (0.1-0.9 microgram g-1) were
      detected in all samples but one. All Lake Knud so and Lake Ravn so samples were
      dominated by Anabaena lemmermannii, and the Lake Salten Langso sample by several
      species of Anabaena. Gel filtration profiles indicated similarity between the
      toxic component from the Lake Knud so 1994 bloom with registered bird-kills and
      anatoxin-a(s) isolated from Anabaena flos-aquae NRC-525-17. Anticholinesterase
      producing cultures of A. lemmermannii were isolated from the Lake Knud so 1993
      bloom. These laboratory cultures produced anatoxin-a(s) equivalents of 29-743
      micrograms g-1. Other cultures of A. lemmermannii isolated from Lake Knud so and
      Lake Ravn so were hepatotoxic or non-toxic. Dead birds collected from Lake Knud
      so during the neurotoxic 1993 Anabaena bloom possibly died from cyanobacterial
      toxicosis. The stomach contents contained colonies and single trichomes of
      Anabaena, and anticholinesterase activities equivalent to 2.1-89.7 micrograms
      anatoxin-a(s) kg-1 body weight and microcystins (53-95 ng kg-1) were also
      detected.

PMID- 9241785
TI  - Molecular characterization, antigenicity and immunogenicity of anatoxic polymeric
      forms conferring protection against scorpion venoms.
AB  - Two polymeric forms of Buthus occitamus tunetanus (Bot) G-50 and Androctonus
      australis hector (Aah) G-50 were obtained by controlled polymerization with
      glutaraldehyde. Their mol. wts, determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and exclusion high-performance liquid
      chromatography using radiolabelled toxin, ranged from 14,000 to 90,000 and 90,000
      to 100,000 for Aah G-50 and Bot G-50, respectively. Modification of about 20% of
      the lysine residues yielded completely detoxified Bot G-50 fractions which
      retained the antigenic cross-reactivity with the native G-50 fraction, venom and
      toxins. High levels of specific antibodies against venoms and toxins were
      generated by immunization with prepared polymeric forms because absorbance values
      higher than 3 units were regularly observed by enzyme-linked immunosorbent assay
      with immune sera dilutions of 1/10,000. In vitro protection experiments
      demonstrated that immune sera from mice, horse and monkeys efficiently
      neutralized either Aah or Bot venom. Depending on the adjuvant and animal model
      species used, the neutralizing titre estimated by subcutaneous injection in mice
      varied between 20 and 40 LD50/ml. The in vivo protection assays showed that
      immunized mice could resist the challenge by six times the LD50 amounts of the
      toxic fraction. This protection was found to be long-lived. It was concluded that
      G-50 polymeric forms are highly detoxified and immunogenic, and should be useful
      for the production of potent polyvalent antivenom against scorpion toxins. They
      could also be considered for further studies towards the development of vaccine
      candidates.

PMID- 9241786
TI  - Neutralization of bothropic and crotalic venom toxic activities by IgG(T) and
      IgGa subclasses isolated from immune horse serum.
AB  - IgG(T) and IgGa isotypes were isolated from horse hyperimmune anti-bothropic and
      anti-crotalic sera using a combination of two affinity chromatographic processes.
      IgG(T) and IgGa isotypes were isolated from these sera by chromatography on
      protein A-Sepharose followed by separation of the two isotypes by chromatography
      on a column of anti-IgG(T)-Sepharose. LO-HoGT-1, a rat anti-horse IgG(T)
      monoclonal antibody, was used. A comparative study of the efficiency of these
      isotypes in neutralizing the main toxic activities of the homologous venoms was
      carried out. It was found that IgG(T) was about three-fold and seven-fold more
      protective than IgGa for neutralization of the lethal activity of B. jararaca and
      C. d. terrificus venoms, respectively. IgG(T) was also more effective than IgGa
      for the neutralization of the haemorrhagic activity induced by B. jararaca venom,
      while both isotypes neutralized equally well the blood incoagulability induced by
      this venom. The results suggest that IgG(T) is the most protective isotype
      present in both anti-bothropic and anti-crotalic sera, followed by IgGa. Owing to
      their very low concentration in the serum, other IgG isotypes are not likely to
      be important in neutralizing the venoms' toxic activities.

PMID- 9241787
TI  - Distribution of tritiated dihydromicrocystin in swine.
AB  - The distribution of tritiated dihydromicrocystin [3H]2H-MCLR was studied in
      anesthetized specific-pathogen-free pigs. Two doses were administered i.m. and
      one dose was given via an isolated ileal loop. At 4 hr after i.v. administration
      of the toxin at 25 micrograms/kg, 64.6% of the total dose (%TD) was located in
      the liver, with smaller amounts distributed to the kidneys (1.2% TD), lungs
      (1.75% TD), heart (0.22% TD), ileum (0.13% TD) and spleen (0.04% TD). A similar
      distribution was found at 4 hr postdosing in pigs given 75 micrograms/kg,
      although the liver contained a lower fraction of the total dose, at 46.99% TD,
      and the kidneys had somewhat more, at 2.19% TD, than the low dose. At the high
      dose, the fractions of the amount given accounted for by the lungs (0.55% TD),
      heart (0.23% TD), ileum (0.20% TD) and spleen (0.07% TD) were similar to those at
      the low dose. The livers of the pigs given 75 micrograms/kg via the ileal loop,
      at 5 hr postdosing, contained 49.5% TD and the ileum had 33.94% TD. Smaller
      amounts were distributed to kidneys (1.04% TD), lungs (0.65% TD), heart (0.81%
      TD) and spleen (0.16% TD). The livers of both groups dosed at 75 micrograms/kg
      contained higher concentrations of toxin, but lower percentages of the total
      dose, than the livers of pigs dosed at 25 micrograms/kg. Larger increases in
      serum arginase in the two 75 micrograms/kg groups were associated with
      histological evidence of more severe liver damage than at the 25 micrograms/kg
      dose. Analysis of radiolabeled compounds from hepatic tissue using fast atom
      bombardment mass spectrometry determined that the primary constituent was [3H]2H
      MCLR, but two minor radioactive components were also isolated. These findings
      indicate that [3H]2H-MCLR is rapidly concentrated in the liver of swine, whether
      given i.v. or via an isolated ileal loop, that at extremely toxic doses uptake is
      slowed, and that it is as toxicologically active as the parent compound.

PMID- 9241788
TI  - A new method for determination of maitotoxin by capillary zone electrophoresis
      with ultraviolet detection.
AB  - Capillary zone electrophoresis with UV detection was applied to the rapid and
      efficient separation of an underivatized phycotoxin, maitotoxin, associated with
      ciguateric fish poisoning. Highly sensitive detection was obtained by UV
      absorption at 195 nm. A detection limit of 50 pg of maitotoxin was achieved at
      this wavelength. Analysis involved using a fused silica capillary coated with a
      hydrophobic phase, polyvinylalcohols. Confirmation of the electrophoretic peak of
      maitotoxin was further evaluated by cytotoxicity on a mammalian fibroblastic cell
      line, BHK 21 C13.

PMID- 9241789
TI  - Anatoxin-a in Irish freshwater and cyanobacteria, determined using a new
      fluorimetric liquid chromatographic method.
AB  - A new sensitive high-performance liquid chromatographic (HPLC) method was used to
      determine anatoxin-a in freshwater, following blooms of cyanobacteria (blue-green
      algae). Anatoxin-a was converted into a highly fluorescent derivative using 4
      fluoro-7-nitro-2,1,3-benzoxadiazole and HPLC analysis gave good linear
      calibrations even at low concentration ranges (1-10 micrograms/liter, r = 0.997).
      The detection limit for anatoxin-a was 0.02 ng/ml, and this new HPLC method
      should prove useful for the routine analysis of potable waters. Anatoxin-a was
      discovered in three major lakes in Ireland using this method and identification
      was confirmed using gas chromatraphy-mass spectrometry (GC-MS), following
      acetylation. Anatoxin-a was found in Anabaena, a planktonic cyanobacterium, as
      well as in a benthic Oscillatoria species. This is the first identification of
      anatoxin-a in Irish freshwater and this toxin was also implicated as the
      causative agent in incidents of fatal canine neurotoxicosis.

PMID- 9241790
TI  - Identification of a new diarrhoetic toxin in shellfish using liquid
      chromatography with fluorimetric and mass spectrometric detection.
AB  - A new toxin, dinophysistoxin-2B (DTX-2B) was isolated from Irish mussels using
      silica chromatography, gel permeation, octadecylsilane solid-phase extraction and
      repeated preparative high-performance liquid chromatography (HPLC).
      Dinophysistoxin-2 (DTX-2) was also isolated from shellfish using the same
      procedures. The separation of these toxins in chromatographic fractions was
      monitored using fluorimetric HPLC following derivatization with 9
      anthrylmethyldiazomethane or 1-bromoacetylpyrene. Flow-injection analysis-mass
      spectrometry (FIA-MS) with an atmospheric pressure ionization (API) and an
      ionspray (ISP) interface showed a mass spectrum dominated by the protonated
      molecule, [M+H]+, at m/z 805 for DTX-2B, thus indicating that this new toxin has
      the same mol.wt as okadaic acid and DTX-2. The low-energy fragment ion spectrum,
      as produced in FIA-MS experiments by up-front collision-induced dissociation of
      the protonated molecule of DTX-2B, showed fragment ions corresponding to
      successive losses of water molecules from the [M+H]+ ion. This low collision
      energy fragmentation pattern is typical of marine polyether toxins such as
      okadaic acid, DTX-2 and DTX-1. These results provide strong evidence that DTX-2B
      is another okadaic acid isomer.

PMID- 9241791
TI  - Proteolytic specificity of rhodostoxin, the major hemorrhagin of Calloselasma
      rhodostoma (Malayan pit viper) venom.
AB  - The proteolytic specificity of rhodostoxin, the major hemorrhagin from
      Calloselasma rhodostoma (Malayan pit viper) venom was investigated using oxidized
      B-chain of bovine insulin as substrate. Six peptide bonds were cleaved: Ser9
      Hist10, His10-Leu11, Ala14-Leu15, Tyr16-Leu17, Gly20-Glu21 and Phe24-Phe25.
      Deglycosylated rhodostoxin, however, cleaved primarily at Arg22-Gly23.

PMID- 9241792
TI  - 14C-labeled microcystin-LR administered to Atlantic salmon via intraperitoneal
      injection provides in vivo evidence for covalent binding of microcystin-LR in
      salmon livers.
AB  - The tissue distribution and clearance of radiolabeled microcystin-LR administered
      to Atlantic salmon via i.p. injection has been re-examined using uniformly 14C
      labeled toxin. Significant differences were found to exist between these results
      and those obtained when fish received an i.p. injection of tritium-labeled
      dihydromicrocystin-LR. In addition, MeOH liver extracts were assayed by both
      phosphatase assay and 14C counts and the results compared with the total levels
      of incorporation determined by digestion and subsequent 14C counting of the same
      live tissues. An attempt to investigate the metabolism and to document the
      putative products was also undertaken. It was found that microcystin-LR was
      extensively metabolized to compounds that are more polar than the parent
      compound.

PMID- 9241793
TI  - Bibliography of toxinology.

PMID- 9241794
TI  - Cloning of the PacB-Ter region from plasmid Mip233 (IncHI3) and their expression
      in E. coli ton, tol mutants.
AB  - A region of the plasmid Mip233 (incompatibility group HI3) encoding the
      phenotypes of resistance to the channel-forming colicins (character PacB) and
      potassium tellurite (Ter), was cloned and studied. Both properties are contained
      in an insert of 2.2 Kbp, being the smallest functional clone (pB22) isolated so
      far. E. coli DH5 alpha pB22 transformants exhibit resistance to the colicins as
      well as to high levels of tellurite (> 1000 micrograms ml-1). Results suggest
      that they are genetically linked forming an inducible operon. pB22 does not show
      significant homology with DNA from other H plasmids. Tests using E. coli ton and
      tol mutants harbouring recombinant pB22 indicate that the product of gene tolC,
      but not that of tonB, is required for the expression of the PacB and Ter
      phenotypes.

PMID- 9241795
TI  - The 1995 list. Proposed new bacterial taxa and proposed changes of bacterial
      names published during 1995 and considered to be of interest to medical or
      veterinary bacteriology. An informational note.

PMID- 9241796
TI  - The 1996 list. Proposed new bacterial taxa and proposed changes of bacterial
      names published during 1996 and considered to be of interest to medical or
      veterinary bacteriology. An informational note.

PMID- 9241797
TI  - Screening for Salmonella with a murine monoclonal antibody M105 detects both
      Felix O1 bacteriophage sensitive and resistant Salmonella strains.
AB  - Ten Felix O1 (FO1) bacteriophage sensitive Salmonella strains as well as their
      phage resistant derivates together with 39 strains of FO1-resistant Salmonella
      were tested for their reactivities with a murine monoclonal antibody, M105, by
      indirect whole cell and competitive ELISA. All FO1 phage sensitive and 48 of the
      49 FO1-resistant Salmonella strains were found to react with M105. The single
      Salmonella strain not reacting with M105 was a FO1 resistant derivative selected
      by exposing the sensitive parent strain to the phage. This M105-negative and FO1
      resistant strain was also found to be a rough mutant without O-antigens and
      possibly lacks the terminal LPS core sugars which form the M105 reactive epitope.

PMID- 9241798
TI  - Typing of Austrian Listeria monocytogenes isolates by automated laser
      fluorescence analysis of randomly amplified polymorphic DNA.
AB  - We used automated laser fluorescence analysis of randomly amplified polymorphic
      DNA (RAPD-Alfa) to study the epidemiology of listeriosis in western Austria.
      There were no discrepancies between RAPD-Alfa patterns and serotypes found in 18
      food isolates and 18 clinical isolates. The results of our study suggest that the
      food isolates typed were not at the origin of the human cases in western Austria.
      Using RAPD-Alfa, it was possible to link 9 out of 16 "sporadic" Listeria
      infections (mother-child cases counted as one) to the occurrence of other cases.
      Our results underline the necessity of epidemiological clarification of
      listeriosis cases as a prerequisite for specific preventive measures by public
      health services (e.g. confiscation of contaminated food products, issue of public
      warnings). To establish the chain of infection, more is needed than just
      speciation of bacteria in incriminated food products. Automated laser
      fluorescence analysis of randomly amplified polymorphic DNA seems a suitable,
      easy and rapid method for the typing of Listeria monocytogenes strains.

PMID- 9241799
TI  - Evaluation of the synergistic haemolysis (CAMP-like) test in the identification
      of motile, mesophilic Aeromonas species.
AB  - Usefulness of the synergistic haemolysis (CAMP-like) test in the identification
      of Aeromonas hydrophila, Aeromonas sobria, and Aeromonas caviae was evaluated,
      using beta-toxin producing Staphylococcus aureus ATCC 25923 and alpha-toxin
      producing Clostridium perfringens ATCC 13124 as sphingomyelinase producing
      indicator strains. The tests were done on Columbia Blood Agar Base supplemented
      with 5% sheep blood (CBA; Difco Laboratories, Detroit, MI, USA). When cultured
      aerobically, 77% of A. hydrophila isolates, 75% of A. sobria isolates, and 23% of
      A. caviae isolates elicited synergistic haemolysis of sheep erythrocytes with the
      beta-toxin producing strain of S. aureus. Anaerobically, using the same indicator
      strain, synergistic haemolysis was given by 91%, 51% and 82% of A. hydrophila, A.
      sobria, and A. caviae, respectively. When alpha-toxin producing C. perfringens
      was used in the test instead of beta-toxin producing S. aureus, 100%, 86%, and
      93% of A. hydrophila, A. sobria, and A. caviae isolates, respectively, showed
      synergistic haemolysis of sheep erythrocytes. Due to the high number of the
      tested isolates of A. hydrophila, A. sobria, and A. caviae giving a positive
      synergistic haemolysis reaction in both atmospheric conditions of culture, this
      test cannot be used to identify any of the three Aeromonas spp. The use of alpha
      toxin producing C. perfringens did not improve discriminatory power of the test.
      Because the nature of the product of Aeromonas spp. responsible for the lytic
      phenomenon is not known, the use of Aeromonas factor and synergistic haemolysis
      terms was proposed rather than CAMP (reaction, test) or CAMP (-like) factor.

PMID- 9241800
TI  - Cell wall-deficient forms (L-forms) of Listeria monocytogenes in experimentally
      infected rats.
AB  - Experimental infections were induced with different bacterial forms of Listeria
      monocytogenes: parental (S-forms), protoplastic (L-forms) and combined inoculum
      of both forms by i.p. injection of rats. The parental bacterial forms (S-forms)
      were isolated up to 7 days after challenge from the peritoneal cavity and the
      liver, while the L-forms were isolated up to 60 days from the peritoneal cavity.
      Continuous adhesion of L-forms on the peritoneal macrophage surface was found by
      scanning-electron microscopy. Erythrocyte and leucocyte count as well as some
      clinical chemistry parameters were measured during infections. They showed
      different dynamics in the three experimental groups. Histomorphological changes
      in the liver (microabscesses and mononuclear cellular granulomas) of infected
      animals were observed. They were less intensive and appeared later in rats
      infected with L-forms. The experiments demonstrated that infections caused by
      parental bacterial forms and by combined inoculum took an acute course, while the
      infection caused by L-forms could be distinguished as a prolonged and persistent
      one.

PMID- 9241801
TI  - Some biochemical properties of the components of Staphylococcus aureus binding to
      human platelets.
AB  - The binding properties of Staphylococcus aureus in relation to human platelets
      were investigated. Protease digestion (pronase E, proteinase K, trypsin), heat
      treatment (80 degrees C, 30 min), and sonication for 5 min significantly reduced
      the binding abilities of the staphylococcal cells to 0% (p < .01), 50 +/- 5% (p <
      .05), and 38 +/- 9% (p < .05), respectively, while mixed glycosidases did not.
      Inhibition experiments indicated that protein A and various sugars were
      ineffective. A binding study using biotinylated cell surface fractions extracted
      from the whole cells of S. aureus indicated that the proteins having apparent
      molecular weights of 14400 and 16500 estimated by sodium dodecylsulfate
      polyacrylamide gel electrophoresis were involved in the binding between S. aureus
      and human platelets.

PMID- 9241802
TI  - Antibacterial activity of trichorabdal A from Rabdosia trichocarpa against
      Helicobacter pylori.
AB  - Rabdosia trichocarpa is used in a popular home-made remedy for gastric and
      stomachic complaints in Japan. A diterpene, trichorabdal A from R. trichocarpa,
      showed a very strong in vitro antibacterial activity against Helicobacter pylori.
      With regard to the antibacterial activity of the extract and constituents of R.
      trichocarpa against H. pylori, the effect of traditional use of this plant for
      the treatment of gastritis is probably due to the suppression of H. pylori since
      the extract of R. trichocarpa particularly inhibits the growth of H. pylori. It
      could be a promising native herb treatment for patients with gastric complaints
      including gastric ulcer caused by H. pylori.

PMID- 9241803
TI  - Further search for virulence factors encoded by Salmonella serovar-specific
      plasmids.
AB  - The so called Salmonella virulence plasmids which are specifically prevalent
      among some of the S. enterica serovars were shown to contribute only marginally
      to the virulence make-up of salmonella, which is in contrast to Shigella and
      Yersinia spp. The experiments reported in this paper failed to find encoded
      plasmid factors which contribute to serum resistance, surface antigens,
      immunoinsufficiency or to up-regulation of chromosomally encoded factors such as
      toxins, surface antigens etc. Taking into consideration the rare prevalence of
      these plasmids among S. enterica but their common occurrence among a few of its
      serovars, their virulence implication remains an enigma.

PMID- 9241804
TI  - Adherence of Salmonella typhimurium to murine peritoneal macrophages is mediated
      by lipopolysaccharide and complement receptors.
AB  - Adherence of Salmonella typhimurium to mouse peritoneal macrophages (Mo) was
      monitored using a direct microscopic assay and flow cytometry. Competitive
      binding studies using wild-type lipopolysaccharide and derivatives confirmed a
      role for this moiety in bacterial adherence. Mo pretreated with 2-deoxy-D-glucose
      exhibited lower binding activity than did untreated controls, suggesting
      involvement of either Fc or complement receptors. Pre-exposing Mo to Fc
      fragments, however, failed to reduce bacterial binding, thus eliminating a role
      for Fc receptors in this process. Mo pretreated with neutrophil elastase
      exhibited a diminished ability to bind S. typhimurium, suggesting involvement of
      complement receptor 1. Monoclonal antibodies M1/70 and M18/2, specific for
      epitopes on the alpha and beta chains, respectively, of complement receptor 3,
      also blocked this adherence. In each case we were unable to eliminate completely
      bacterial adhesion to Mo. Monoclonal antibodies to two additional Mo receptors,
      Mac-2 and Mac-3, did not block bacterial attachment. These data indicate that
      multiple mechanisms are involved in the initial adhesion of S. typhimurium to
      mouse Mo.

PMID- 9241805
TI  - The etiological agent of Lyme disease, Borrelia burgdorferi, in ticks
      (Acari:Ixodidae) from eastern Poland.
AB  - In 1994, 4204 out of 4656 Ixodes ricinus collected both from vegetation in three
      different areas and from hunter-killed deer and wild boar in the Bialystok
      province (eastern Poland) were examined individually for the presence of Borrelia
      burgdorferi s.I. Detection of spirochetes was carried out by the routine indirect
      immunofluorescence assay (IFA) using polyclonal antibody (anti-B. burgdorferi,
      strain 1 B 29). B. burgdorferi spirochetes were evident in 349 (8.8%) nymphal and
      adult I. ricinus collected from vegetation (n = 3958) and in 8 (3.2%) of those
      removed from hosts (n = 246). Among the ticks collected from vegetation,
      infection rates in nymphs (5.8-6.4%) in particular areas were about 2-4 times
      lower than in adults (8.1-24.6%). The calculated minimal and maximal infection
      rates of ticks collected from different sites were 1.6% and 15.4%, respectively.
      Prevalence of B. burgdorferi in I. ricinus was determined with respect to the
      abundance and seasonal activity of the ticks.

PMID- 9241806
TI  - Development of a new CSF-shunt with sustained release of an antimicrobial broad
      spectrum combination.
AB  - The use of Cerebro-Spinal-Fluid-shunts (CSF-shunts) is often associated with
      infectious complications, because bacteria tend to colonize plastic material. The
      use of plastic materials with antibacterial activity may reduce catheter related
      bacterial colonization. A novel CSF-shunt impregnated with a broad-spectrum
      antimicrobial combination was designed in order to meet two requirements; lack of
      toxicity and persistence of antimicrobial efficacy. Incorporation of three
      antibiotics up to 10% (wt/wt) into the shunt material (polydimethyl-siloxane) was
      required for sustained release for more than 100 days, measured by HPLC. The
      combination of antimicrobials showed additive and synergistical effects as
      measured by the checker-board and time kill technique. These antimicrobial
      combinations prevented mutations in resistance inducing experiments with several
      S. epidermidis and S. aureus strains. Using large challenge doses of S. aureus in
      a catheter colonization model, antimicrobially modified catheters were protected
      against bacterial colonization for more than 14 days. Using a C3a-des-Arg-ELISA
      test and a CH50-hemolysis test the modified catheter was as biocompatible as the
      unmodified shunt material. These encouraging results indicate that such
      antibiotic-bonded catheters substantially reduce the incidence and magnitude of
      catheter-related bacterial colonization and may substantially reduce CSF-shunt
      infection.

PMID- 9241807
TI  - Tick-borne encephalitis virus (TBEV)-specific RT-PCR for characterization of
      natural foci of TBE and for other applications.
AB  - An effective detection system for TBEV-RNA sequences using a RT-PCR technique has
      been developed. In our system, specific oligonucleotide primers corresponding to
      the 5'-terminal noncoding region were successfully used to identify TBEV
      sequences in ticks. To prove the specificity of the PCR products, Southern blot
      hybridization with an internal digoxigenin-labelled probe was carried out. In
      this paper, we present some potential applications of this technique. The primers
      were used to identify 21 TBEV strains isolated in different years, in different
      geographic regions and from different sources. 22313 Ixodes ricinus ticks from
      north-east Germany were analyzed for TBEV-specific sequences in order to
      characterize the viral activity in natural foci of TBE. In the new Federal
      Lander, only 6 samples gave positive PCR-results, showing that the natural foci
      of TBE had not been extinguished but remained in a state of endemic latency. We
      also used the RT-PCR to develop an animal model to investigate the temporal
      pattern of viraemia in the Mongolian gerbil (Meriones unguiculatus) through
      xenodiagnosis (sequential tick feeding on an infected host and subsequent RT-PCR
      testing of the resultant engorged ticks).

PMID- 9241808
TI  - Examination of soils from residential garbage in Betul, India, for fungi by the
      keratin baiting technique.
AB  - A report on an examination of soils from residential garbage of Betul, India, for
      fungi by the keratin (materials) baiting technique is presented. A total of 69
      fungi representing 39 species among 17 genera were isolated. In all the soil
      samples, only two genera, namely Aspergillus (190.9%), followed by Fusarium
      (118.18%), were most frequently isolated. Maximum colonisation of fungi was found
      on hair, followed by horn, feathers and nails. For the first time, the genus
      Fusoma is reported here as a keratinophilic fungus. The keratin baiting technique
      was found very effective in detecting a broad spectrum of fungi in biological
      wastes and compost.

PMID- 9241809
TI  - Rapid assessment of onchocerciasis prevalence and a model for selecting
      communities for ivermectin distribution in West Africa.
AB  - Analysis of the prevalence of onchocerciasis in an area of north-east Nigeria
      indicates that clinical symptoms are generally good predictors of the rate of
      onchocerciasis infection and of the mean microfilarial density in infected
      individuals. However, differences between regions and anomalous communities
      within regions make reliance on a single indicator dubious. Use of multivariate
      equations was tested, but offered little improvement over bivariate ones and an
      algorithmic approach, making use of local knowledge of factors which might
      complicate interpretation, is proposed instead. The framework is suggested as a
      basis for screening, although a larger database is required to produce definitive
      equations.

PMID- 9241810
TI  - (E,Z)-2-(2-chloro-5-nitrostyryl)-1-(1-propenyl)benzimidazole.
AB  - The title compound, C18H14ClN3O2, was synthesized by the condensation of 2-chloro
      5-nitrobenzaldehyde with 2-methyl-1-propenylbenzimidazole, and the molecule
      comprises a 2-chloro-5-nitrobenzene and a 1-(Z)-propenylbenzimidazole. The two
      aromatic moieties are conjugated through the vinyl group. The dihedral angle
      between the two rings is 1.4(6) degrees. The propenyl group lies out of the
      benzimidazole plane with a dihedral angle of 112.9(9) degrees.

PMID- 9241811
TI  - Absolute configuration of (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), a
      metabotropic glutamate receptor antagonist.
AB  - The title compound, (+)-MCPG [(+)-alpha-(4-carboxyphenyl)-alpha-methylglycine,
      C10H11NO4], is an antagonist at certain subtypes of metabotropic glutamate (mGlu)
      receptors. (+)-MCPG has gained widespread acceptance as a tool for probing the
      physiological role of mGlu receptors in the central nervous system. As a result,
      mGlu receptors are now known to be involved in processes connected with learning
      and memory, modulation of synaptic transmission and the transmission of pain
      responses. (+)-MCPG crystallized in its zwitterionic form. Its absolute
      configuration was assigned as S from X-ray diffraction data collected at 150 K.
      The refined Flack parameter is consistent with this assignment, although the
      large e.s.d. associated with it introduces some ambiguity.

PMID- 9241812
TI  - 1-Acetyl-3-hydroxyadamantane and 1-carboxy-3-hydroxyadamantane.
AB  - The crystal structures of the adamantane derivatives, 1-acetyl-3-adamantanol,
      C12H18O2, (4), and 3-hydroxyadamantane-1-carboxylic acid, C11H16O3, (5), have
      been determined by X-ray diffraction. Both structures show extensive
      intermolecular hydrogen bonding involving the hydroxyl and acetyl groups in
      compound (4), and the hydroxyl and carboxyl groups in compound (5).

PMID- 9241813
TI  - Interwoven hydrogen-bonding networks in benzene-1,3,5-triacetic acid.
AB  - The title compound, C12H12O6, crystallized in the centrosymmetric space group
      P21/n. Each molecule is hydrogen bonded to four others by ten hydrogen bonds
      forming a three-dimensional network. Two sets of such networks, which are not
      linked, comprise the structure. The carboxyl O atoms are ordered, as are the
      carboxyl H atoms. The best-fit acetic acid group planes make dihedral angles of
      84.3 (1), 89.8 (2) and 58.0 (2) degrees with the best-fit benzene core plane.

PMID- 9241814
TI  - Clinical trials of malaria vaccines: progress and prospects.

PMID- 9241815
TI  - Phylogeny of the tissue cyst-forming coccidia.

PMID- 9241816
TI  - Biochemistry of the coccidia.

PMID- 9241817
TI  - Genetic transformation of parasitic protozoa.

PMID- 9241818
TI  - The radiation-attenuated vaccine against schistosomes in animal models: paradigm
      for a human vaccine?

PMID- 9241819
TI  - A pharmacokinetic analysis of interspecies extrapolation in dioxin risk
      assessment.
AB  - This study entails a pharmacokinetic analysis of the relationship between the
      external dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD) and resulting
      concentrations of TCDD in internal tissues and organs of humans and rodent
      species. The methodology is based on the development and testing of
      physiologically based pharmacokinetic models for several rodent species and
      humans. The results indicate that the relationship between the external dose of
      TCDD and resulting TCDD concentrations in liver and adipose tissue of humans and
      various species of rats and mice can vary by as much as 725 fold, illustrating
      that humans and experimental animals differ considerably in their ability to
      convert external dosages of dioxin to tissue concentrations. Interspecies scaling
      factors are reported to express the differences in tissue concentrations of
      dioxin between mice, rats and humans in response to an equivalent external dose.
      The significance of these findings for conducting human cancer and ecological
      risk assessments is discussed. It is recommended that pharmacokinetic differences
      be considered explicity in risk estimation, while separately recognizing
      interspecies differences in pharmacodynamics (sensitivity).

PMID- 9241820
TI  - PCDD/PCDF from emission sources and ambient air in northeast Spain.
AB  - PCDD/PCDF were detected and quantified in emissions from municipal and industrial
      waste incinerators. Levels of PCDD/PCDF in ambient air were measured in order to
      evaluate the possible influence. Identification and quantification were carried
      out by HRGC/HRMS with isotopic dilution as a quantification method using two
      different GC columns: J&W DB-5 and J&W DB-DIOXIN.

PMID- 9241822
TI  - Coplanar PCBs and the relative contribution of coplanar PCBs, PCDDs, and PCDFs to
      the total 2,3,7,8-TCDD toxicity equivalents in human serum.
AB  - Coplanar PCBs in human serum were measured by high-resolution gas
      chromatography/isotope-dilution high-resolution mess spectrometry in 46 pulp and
      paper mill workers and 16 community residents with no specific known source of
      PCB exposure. The relative contribution of coplanar PCBs, PCDDs, and PCDFs to the
      total 2,3,7,8-TCDD toxicity equivalents (TEQs) were compared using the toxic
      equivalency factors proposed by Safe [1] and the factors recently proposed by WHO
      [2]. The mean concentrations of PCB-126 and PCB-169 were higher in paper mill
      workers than in community residents. However, these differences were not
      statistically significant. Serum PCB-126, but not PCB-169, was correlated with
      body mass index (Spearman's r = 0.40, p = 0.002). Serum PCB-169, but not PCB-126,
      was correlated with age (Spearman's r = 0.54, p = 0.0001). Multiple linear
      regression analysis for log-transformed combined PCBs showed that age (p =
      0.008), body mass index (p = 0.031), and eating locally caught fish (p = 0.019)
      were statistically significant predictors. The majority of the total TEQ in serum
      is due to PCDDs (63%), whereas PCDFs account for 21% and coplanar PCBs account
      for 15% when calculated using the TEFs proposed by Safe. The percent
      contributions from PCDDs, PCDFs, and coplanar PCBs were 66%, 24%, and 10%
      respectively when calculated based on the TEFs proposed by WHO. Age, body mass
      index, and consumption of locally caught fish are significant predictors for
      coplanar PCB levels in human serum. Serum PCDDs were the major contributors to
      the total 2,3,7,8-TCDD equivalent toxicity in this study.

PMID- 9241825
TI  - Research on heterocyclic compounds. XXXVIII. Synthesis and pharmacological
      activity of imidazo[1,2-b]pyridazine-2-carboxylic derivatives.
AB  - A series of imidazo[1,2-b]pyridazine-2-carboxylic acids, esters and amides was
      synthesized and tested for antiinflammatory, analgesic and ulcerogenic
      activities. The ethyl esters were prepared by cyclocondensation of some 3
      aminopyridazines with ethyl bromopyruvate, followed by hydrolysis or ammonolysis
      in order to obtain the corresponding acids and amides. The inhibitory activity on
      the carrageenan-induced edema in the rat paw and on writhes induced by acetic
      acid in mice was evaluated, as well as the ulcerogenic action on the rat gastric
      mucosa. The pharmacological activity was discussed in terms of structure-activity
      relationships. In particular, the analgestic activity shown by these carboxylic
      derivatives was compared with that found in other series of imidazo[1,2
      b]pyridazine analogues previously examined.

PMID- 9241826
TI  - Synthesis, estrogen receptor binding affinity and biological evaluation of some 2
      substituted estrone derivatives.
AB  - This report details the preparation of modified estrogens which are structurally
      designed to possess estrogenic and/or antiestrogenic activity. The prominent
      feature of these estrogens is the introduction of a novel side chain in the 2
      position of ring A of the steroid nucleus. Their synthesis includes the use of
      transformations based upon Mannich base chemistry: preparation of the
      intermediate 2-dimethylamino-methylestrone via aminomethylation of estrone and
      introduction of various functionalities via reaction of this Mannich base with
      different reagents. When evaluated for their interaction with the estrogen
      receptor by competitive binding assays, the tested products were found to be
      relatively weak competitors at 0 degree C. The uterotrophic and post-coital
      antifertility assays indicated effects varying in magnitude relative to
      estradiol. Ethyl[(2'-acetyl-3'-(3-hydroxyestra-17-oxo-1,3,5 (10)-trien-2
      yl)]propionate (15) showed uterotrophic and antiimplantation activities of 95%
      and 20% respectively.

PMID- 9241827
TI  - Synthesis and antiparasitic activities of amidinic azolated derivatives.
AB  - A set of heterocyclic N-acetamidinium hydrochlorides were prepared from the
      corresponding N-acetonitriles. The antiparasitic screening showed that, while all
      amidines are practically inactive, some nitriles present leishmanicide
      properties.

PMID- 9241828
TI  - Synthesis, antimicrobial and genotoxic properties of some benzoimidazole
      derivatives.
AB  - A number of 1H-benzoimidazol-2-ylamine and of 1-methyl-1H-benzoimidazol-2-ylamine
      derivatives were synthesized and the crystal and molecular structure of N-[4-(2
      amino-benzoimidazole-1-sulfonyl)-phenyl] acetamide was determined by X-ray
      diffraction analysis. The compounds obtained were investigated for antimicrobial
      and genotoxic activities.

PMID- 9241829
TI  - Synthesis and pharmacological activity of 2-(substituted phenyl)-3-[2 or 3-[(4
      substituted phenyl-4-hydroxy)piperidino]ethyl or propyl]-1,3-thiazolidin-4-ones.
AB  - A series of aryl-hydroxy-piperidinoalkyl-thiazolidinones was synthesized and
      evaluated to inhibit castor oil-induced diarrhea in mice. The dose dependent
      antidiarrheal activity of the most active compound 2-(p-nitrophenyl)-3-?2-[(4-(p
      chlorophenyl)-4-hydroxy)piperidino]ethyl]- 1, 3-thiazolidin-4-one (6) was
      counteracted by naloxone, resulting comparable with that of loperamide, a mu
      opiate agonist.

PMID- 9241830
TI  - 2,5-Diketopiperidine derivatives as non-peptide ligands for cholecystokinin
      receptors.
AB  - Easily accessible 2,5-diketopiperidines have been used as templates for the
      construction of Trp-Phe and Trp-Asp-Phe-NH2 mimics. The cycle [L-Trp psi[COCH2]-L
      Phe] analogue 1a has shown to possess significant and selective affinity for CCKA
      receptors.

PMID- 9241831
TI  - Synthesis and antimycobacterial activity of some new 3-heterocyclic substituted
      chromones.
AB  - The aldol synthesis of benzimidazole, benzothiazole and benzothiazolium salt
      derivatives of chromones is described. The structures of the compounds have been
      proved by elemental analysis and 1H NMR spectra. The antimycobacterial activity
      of some of the prepared compounds have been tested in vitro against Mycobacterium
      tuberculosis (H37Rv) and Mycobacterium fortuitum (1021).

PMID- 9241832
TI  - Synthesis of new 2-arylidene-2H-1,4-benzoxazin-3(4H)-ones.
AB  - A number of 2-arylidene-2H-1,4-benzoxazin-3(4H)-ones were synthesized and
      evaluated for CNS activity. Some of the tested compounds exhibited marked CNS
      depressant activity in mice.

PMID- 9241833
TI  - 3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles: synthesis and
      evaluation for antimicrobial and antiviral activity. III.
AB  - A series of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole
      derivatives was prepared and tested to evaluate their antimycotic, antibacterial
      and anti-HIV-1 activities. The reaction of thiocarbohydrazide with carboxylic
      acids at the melting temperature allows an improved preparation of the 5
      substituted 4-amino-3-mercapto-1,2,4-triazole heterocycles which in turn allows
      an easier preparation of the 1,2,4-triazolo[3,4-b] [1,3,4]thiadiazole ring
      system. All tested compounds didn't show any significant activity.

PMID- 9241834
TI  - Liquid chromatographic determination of monensin in premix and animal feeds:
      collaborative study.
AB  - An interlaboratory study of a liquid chromatographic (LC) method for determining
      monensin in premix (60-80 g/lb or 132-176 mg/g) and animal feeds (5-200 g/ton or
      0.0055-0.22 mg/g) was conducted in laboratoriesin the United States, Canada,
      France, and Germany. The LC system used a reversed-phase column, postcolumn
      derivatization with vanillin, and UV detection. The method separates monensin
      from other ionophores such as narasin and salinomycin. Each laboratory analyzed a
      total of 20 samples of premix, liquid feed supplements, poultry, and cattle
      feeds. Concentrations of monensin in all samples ranged from 0 to 176 mg/g (80
      g/lb). Reproducibility relative standard deviation (RSDR) for premix ranged from
      2.8 to 3.4%. For feed samples containing monensin, repeatability standard
      deviation (sr) ranged from 0.9 to 7.0. Reproducibility standard deviation (sR)
      ranged from 1.2 to 11. Repeatability relative standard deviation (RSDr) ranged
      from 6.1 to 21% and RSDR values-ranged from 8.6 to 25%. Sample preparation for
      the LC method is less labor intensive than that for the microbiological assays.
      The LC assay is more efficient than the microbiological assays. This LC method
      for determination of monensin in premix and animal feeds has been adopted first
      action by AOAC INTERNATIONAL.

PMID- 9241835
TI  - Colorimetric determination of selenium in mineral premixes .
AB  - A method is described for determination of sodium selenite or sodium selenate in
      mineral-based premixes. It is based on the formation of intense-yellow
      piazselenol by Se(IV) and 3,3'-diaminobenzidine. Mineral premixes typically
      contain calcium carbonate as a base material and magnesium carbonate, silicon
      dioxide, and iron(III) oxide as minor components or additives. In this method,
      the premix is digested briefly in nitric acid, diluted with water, and filtered
      to remove any Iron(III) oxide. Ethylenediaminetetraacetic acid and HCl are added
      to the filtrate, which is heated to near boiling for 1 h to convert any selenate
      to selenite. After heating, the solution is buffered between pH 2 and 3 with NaOH
      and formic acid and treated with NH2OH and EDTA; any Se present forms a complex
      with 3,3'-diaminobenzidine at 60 degrees C. The solution is made basic with
      NH4OH, and the piazselenol is extracted into toluene. The absorbance of the
      complex in dried toluene is measured at 420 nm. The method was validated
      independently by 2 laboratories. Samples analyzed included calcium carbonate
      fortified with 100, 200, and 300 micrograms Se in the form of sodium selenite or
      sodium selenate, a calcium carbonate premix containing sodium selenite, a calcium
      carbonate premix containing sodium selenate, and a commercial premix; 5
      replicates of each sample type were analyzed by each laboratory. Average
      recoveries ranged from 89 to 109% with coefficients of variation from 1.2 to
      13.6%.

PMID- 9241836
TI  - Determination of ethoxyquin in feeds by liquid chromatography: collaborative
      study.
AB  - Ethoxyquin is a chemical antioxidant used in feeds, ingredients, fats, and oils.
      A liquid chromatographic (LC) method for determination of ethoxyquin was
      developed. The method involves acetonitrile extraction of the sample and
      isocratic C18 reversed-phase chromatography with ammonium acetate buffer
      acetonitrile as mobile phase and fluorescence detection. A collaborative study of
      the determination of ethoxyquin in various meals and extruded pet foods was
      conducted by The Iams Company Research Laboratory. Eleven laboratories analyzed
      16 samples (including 2 blind duplicates) consisting of 7 meat meals and 9
      extruded pet foods. Sample means ranged from 0.25 to 289 ppm. Repeatability
      standard deviations ranged from 0.08 to 3.2 ppm, and repeatability relative
      standard deviations ranged from 4.5 to 32%. Reproducibility standard deviations
      ranged from 0.12 to 13 ppm, and reproducibility relative standard deviations
      ranged from 4.5 to 55%. The LC method for determination of ethoxyquin in feeds
      has been adopted first action by AOAC INTERNATIONAL.

PMID- 9241837
TI  - Liquid chromatographic analysis of bacitracin methylene disalicylate in feed.
AB  - Because of its peptide structure, bacitracin is not chemically distinct from many
      matrixes such as feeds or residue samples. Thus, bacitracin must be isolated from
      the matrix components or chemically altered to form a distinct component. Because
      of the complexity of this problem, bacitracin is still analyzed almost
      exclusively by microbiological methods. However, advances in solid-phase
      extraction has made sample isolation from the matrix much more practical. In this
      investigation both strong-cation exchange and C8 columns were used to isolate
      bacitracin for liquid chromatographic (LC) analysis. Results of both LC and
      microbiological analyses are compared.

PMID- 9241838
TI  - Planar chromatography for the multiclass, multiresidue screening of
      chloramphenicol, nitrofuran, and sulfonamide residues in pork and beef.
AB  - A method is described for multiclass and multiresidue qualitative detection of
      chloramphenicol, nitrofuran, and sulfonamide residues in animal muscle. The drugs
      are extracted from 1 g tissue with 2 mL ethyl acetate and purified by silica
      solid-phase extraction. After elution of the cartridge, the collected solution is
      evaporated, and the residue is dissolved in methanol and chromatographed on a
      Si60 high-performance thin-layer chromatography plate. After evaporation of
      solvent, nitrofurans are visualized first by their specific UV photochemical
      reaction with pyridine. Then chloramphenicol is reduced to its amino derivative,
      and this derivative and the sulfonamides are visualized by long-wave UV after
      reaction with fluorescamine. Chloramphenicol, nitrofurans, and sulfonamides are
      detected at residue level of 10, 5, and 100 micrograms/kg, respectively, or less
      in pork and beef.

PMID- 9241839
TI  - Planar chromatographic and liquid chromatographic analysis of thiamphenicol in
      bovine and human plasma.
AB  - A planar chromatographic (PC) method was developed to determine thiamphenicol in
      human and bovine plasma with florphenicol as internal standard. The performance
      of the method was compared with that of a liquid chromatographic method. Recovery
      of extraction method developed for plasma was 81.51 +/- 2.85%. Reproducibilities
      of the PC assay performed with various PC plates were also good.

PMID- 9241840
TI  - Determination of sulfonamides in edible salmon tissue by liquid chromatography
      with postcolumn derivatization and fluorescence detection.
AB  - Fourteen sulfonamides-sulfanilamide, sulfadiazine, sulfathiazole, sulfapyridine,
      sulfamerazine, sulfamethazine, sulfamethizole, sulfamethoxypyridazine,
      sulfachloropyridazine, sulfamonomethoxine, sulfadoxine, sulfamethoxazole,
      sulfadimethoxine, and sulfaquinoxoline-residues of which could be found in
      aquacultured species, were separated in < 25 min by reversed-phase (C18) liquid
      chromatography (LC) with gradient elution. Analytes were extracted from edible
      salmon tissue (muscle and adhering skin) with acetonitrile-2% aqueous acetic
      acid, isolated with 2 liquid-liquid partitionings, and derivatized with
      fluorescamine after eluting from the column. The derivatives were detected by
      fluorescence. Recoveries (n = 4) from coho salmon fortified with sulfonamides at
      5, 10, and 20 ng/g tissue averaged 79.7 +/- 7.3, 84.6 +/- 7.7, and 88.2 +/- 7.1%,
      respectively. Limits of quantitation were 5 ng/g tissue, for sulfanilamide,
      sulfamethoxypyridazine, and sulfaquinoxoline and 1 ng/g tissue for the remaining
      sulfonamides.

PMID- 9241841
TI  - Liquid chromatographic determination of thalidomide in tablets, capsules, and raw
      materials.
AB  - A simple, isocratic liquid chromatographic method for assay of thalidomide in
      tablets, capsules, and raw materials was developed. The method uses a Nova-Pak
      octadecylsilane bonded-phase column (150 x 3.9 mm, 4 microns particle size), a
      mobile phase of acetonitrile-water (15 + 85), a flow rate of 1 mL/min, detection
      at 237 nm, and phenacetin as internal standard. Phosphoric acid was used in
      preparation of sample solutions to inhibit thalidomide hydrolysis. Assays ranged
      from 99.3 to 100.4% in raw materials from 4 manufacturers, from 79.7 to 104.8% in
      tablets from 7 manufacturers, and from 75.3 to 102.6% in capsules from 4
      manufacturers. Assay method precisions for triplicate analyses on 5 days were
      0.30% for tablets, 0.22% for capsules, and 0.22% for raw materials. Recovery from
      simulated tablet formulations was 100%. The method has been used to analyze
      individual tablets and capsules for determination of content uniformity.

PMID- 9241842
TI  - Assurance polyclonal enzyme immunoassay for detection of Listeria monocytogenes
      and related Listeria species in selected foods: collaborative study.
AB  - Six foods representing a variety of food products were analyzed by the Assurance
      Listeria polyclonal enzyme immunoassay (EIA) and by either the Bacteriological
      Analytical Manual or the U.S. Department of Agriculture culture method for
      detecting Listeria monocytogenes and related Listeria species. Samples of each
      food type, at each inoculation level, were analyzed simultaneously by both
      methods. A total of 19 laboratories representing federal government agencies and
      private industry in the United States and Canada participated. Food types were
      inoculated with Listeria species including L. monocytogenes, with the exception
      of 3 lots of green beans, which were naturally contaminated. During this study,
      1764 samples and controls were analyzed and confirmed, of which 492 were positive
      and 947 were negative by both methods. There were 159 samples that were positive
      by culture method but negative by the EIA and 188 that were negative by culture
      method but positive by EIA. Twenty-two samples were negative by EIA and by
      culture method but confirmed positive when Assurance selective enrichment broths
      were subcultured to selective agar. The Assurance polyclonal EIA for detecting L.
      monocytogenes and related Listeria species in foods has been adopted first action
      by AOAC INTERNATIONAL.

PMID- 9241843
TI  - Visual immunoprecipitate assay (VIP) for Listeria monocytogenes and related
      Listeria species detection in selected foods: collaborative study.
AB  - Six foods representing a variety of food products were analyzed by the Visual
      Immunoprecipitate Assay (VIP) and either the Bacteriological Analytical Manual
      (BAM) or the U.S. Department of Agriculture culture methods for detection of
      Listeria monocytogenes and related Listeria spp. Samples of each food type at
      each inoculation level were simultaneously analyzed by both methods. A total of
      23 laboratories representing federal agencies and private industry in the United
      States and Canada participated in this collaborative study. Foods were inoculated
      with Listeria species including L. monocytogenes, with the exception of 3 lots of
      green beans that were naturally contaminated. During this study, 1509 samples and
      controls were analyzed and confirmed, of which 370 were positive and 921 were
      negative by both methods. One hundred and fifteen samples were positive by
      culture methods but negative by VIP. One hundred and thirty-two were negative by
      culture methods but positive by the VIP. Twenty-nine samples were negative by VIP
      and by culture methods but confirmed positive when VIP selective enrichment
      broths were subcultured to selective agars. The VIP method for detection of L.
      monocytogenes and related Listeria spp. in foods has been adopted first action by
      AOAC INTERNATIONAL.

PMID- 9241844
TI  - Comparison of the Petrifilm dry rehydratable film and conventional culture
      methods for enumeration of yeasts and molds in foods: collaborative study.
AB  - A collaborative study was performed involving 18 laboratories and 6 food types to
      compare 3M Petrifilm yeast and mold count plates with the method described in the
      U.S. Food and Drug Administration's Bacteriological Analytical Manual. Four
      species of mold and 2 species of yeast were used to inoculate the following
      foods: hot dogs, corn meal, ketchup, orange juice, yogurt, and cake mix. Each
      collaborator received 15 samples of each food type: 5 low-level inoculations, 5
      high-level inoculations, and 5 uninoculated samples. There was no significant
      difference between the means of the 2 methods for any product or inoculation
      level. The Petrifilm yeast and mold count plate method for enumeration of yeasts
      and molds in foods has been adopted first action by AOAC INTERNATIONAL.

PMID- 9241845
TI  - Fumonisin levels in Uruguayan corn products.
AB  - A survey was conducted to evaluate fumonisins FB1 and FB2 in Uruguayan corn
      products. Sixty-four samples of different local brands were purchased from retail
      stores during a 15-month period and analyzed for FB1 and FB2 by methanol-water
      extraction, cleanup with a 1 mL. strong-anion-exchange solid-phase extraction
      column, and liquid chromatography with o-pthaldialdehyde-2-mercaptoethanol
      derivatization and fluorescence detection. Contamination levels for FB1 varied
      from 50 ng/g (detection limit) to 6342 ng/g. Values were highest in feed samples
      (up to 6342 ng/g), unprocessed corn kernel (up to 3688 ng/g), and milled
      products, which included polenta (up to 427 ng/g). They were lowest in processed
      corn kernel (up to 155 ng/g) and snacks (up to 314 ng/g). FB2 was determined in
      one-fourth of the total samples and detected at trace levels in only one feed
      sample. The data demonstrated the natural occurrence of fumonisins in corn
      products in Uruguay. Feed and polenta that contain fumonisins could be of concern
      because they are consumed in large amounts and are often the main nutrient source
      in Uruguay.

PMID- 9241846
TI  - Extension of dry ash atomic absorption and spectrophotometric methods to
      determination of minerals and phosphorus in soy-based, whey-based, and enteral
      formulae (modification of AOAC Official Methods 985.35 and 986.24): collaborative
      study.
AB  - Eight laboratories participated in a collaborative study of AOAC Official Method
      985.35, Minerals in Ready-to-Feed Milk-Based infant Formula and Pet Foods, Atomic
      Absorption Spectrophotometric Method; and 7 laboratories participated in a study
      of AOAC Official Method 986.24, Phosphorus in Milk-Based infant Formula,
      Spectrophotometric Method, to extend these methods to infant formulae (other than
      milk-based) and enteral products. Three ready-to-feed soy-based formulae and 2
      soy-based powder formulae were chosen to represent the plant matrix. A whey-based
      formula and a casein-based enteral formula were also included in the study. Soy
      formulae containing nearly identical concentrations of particular elements were
      matched, and an application of the Youden "closely matched pair" approach was
      used to estimate repeatability parameters. Average reproducibility values were as
      follows: calcium, 9.3%; copper, 9.7%; Iron, 5.5%; potassium, 4.0%; magnesium,
      5.2%; manganese, 10.6%; sodium, 4.7%; phosphorus, 10.5%; and zinc, 7.3%. At
      similar analyte concentrations, the between-laboratory variabilities compared
      well with those reported for the official methods. Most repeatability and
      reproducibility parameters compared well with the original collaborative study.
      AOAC Official Methods 985.35 and 966.24 have been modified to extend their
      applicability to infant formulae (other than milk-based) and enteral products.

PMID- 9241848
TI  - Gas chromatographic determination of cyprodinil, fludioxonil, pyrimethanil, and
      tebuconazole in grapes, must, and wine.
AB  - A rapid and simple gas chromatographic method for determinating cyprodinil,
      fludioxonil, pyrimethanil, and tebuconazole in grapes, must, and wine is
      described. An on-line microextraction method was used with a one-step extraction
      partition procedure. Nitrogen-phosphorus and mass spectrometric detectors were
      used, because of their low sensitivity and high selectivity. Because of high
      selectivity of detector, no cleanup was necessary and the extract was
      concentrated 5 times. Recoveries from fortified grapes, must, and wine ranged
      from 93 to 110%. Limits of determination were 0.05 mg/kg for cyprodinil and
      pyrimethanil and 0.10 mg/kg for fludioxonil and tebuconazole.

PMID- 9241849
TI  - Determination of sodium in biological materials by instrumental neutron
      activation analysis.
AB  - A formalized method for determining sodium in biological materials by
      instrumental neutron activation analysis is presented. The method includes common
      procedures from the numerous options available to this historically nonformalized
      analytical technique. The number of procedural options is restricted to minimize
      the method's complexity, yet the method is still applicable to a variety of
      neutron activation facilities. High accuracy and precision are achieved by
      placing bounds on allowed uncertainty at critical stages of the analysis.
      Analytical results from the U.S. Food and Drug Administration laboratory and 4
      other laboratories demonstrate the method's performance.

PMID- 9241847
TI  - Taurine analysis in milk and infant formulae by liquid chromatography:
      collaborative study.
AB  - A collaborative study was conducted on a liquid chromatographic (LC) method for
      determination of taurine in infant formula and milk powders. Twenty laboratories
      participated in the analysis of 8 blind duplicates over the range of
      approximately 3-60 mg/100 g sample. The method involved protein removal,
      conversion to the dansyl-derivative, and isocratic LC separation with UV and/or
      fluorescence detection. Following outlier treatment, overall mean RSDR has been
      estimated at 7.00% for supplemented products with a HORRAT value of 1.1. The
      poorer precision at endogenous levels establishes a lower limit of determination
      of about 5 mg/100 g. An overall mean RSDr:RSDR value of 0.7 for all products
      demonstrated acceptable performance.

PMID- 9241850
TI  - Monitoring of domestic and imported apples and rice by the U.S. Food and Drug
      Administration pesticide program.
AB  - In 1993-94, the U.S. Food and Drug Administration (FDA) conducted a statistically
      based study of pesticide residues in domestic and imported fresh apples and
      processed rice. For apples, 769 domestic and 1062 imported samples were collected
      and analyzed; 85% of the domestic and 86% of the imported samples had detectable
      residues. Benomyl, a widely used fungicide, was found with greatest frequency in
      domestic apples, while diphenylamine was found most often in imported apples. One
      domestic and 4 imported samples contained violative residues of pesticides for
      which there are no U.S. tolerances on apples. The statistically weighted (by
      domestic packer throughput or import shipment size) violation rates for domestic
      and imported apples were 0.30% (0.13 unweighted) and 0.41% (0.38 unweighted),
      respectively. For rice, 598 domestic and 612 imported samples were collected and
      analyzed; 56% of the domestic and 12% of the imported samples had detectable
      residues. Malathion had the greatest frequency of occurrence in both groups of
      rice. Eight domestic and 9 imported samples were violative, all as a result of
      use of pesticides for which there are no U.S. tolerances on rice. The
      statistically weighted violation rates for domestic and imported rice were 0.43%
      (1.3 unweighted) and 1.1% (1.5 unweighted), respectively. Results of the
      statistically based study show that, as in FDA's regulatory monitoring, the
      levels of most pesticide residues found in these 2 commodities are generally well
      below U.S. tolerances, and few violative residues are found.

PMID- 9241851
TI  - International proficiency testing of analytical laboratories for foods and feeds
      from 1990 to 1996: the experiences of the United Kingdom Food Analysis
      Performance Assessment Scheme.
AB  - The Food Analysis Performance Assessment Scheme (FAPAS) organized by a
      Secretariat of the UK Ministry of Agriculture, Fisheries, and Food has checked
      the proficiency of analytical laboratories for foods and feeds from 1990 to 1996.
      FAPAS was started for UK laboratories but was expanded worldwide at the request
      of analysts in other countries who did not have a home-based scheme. Thirteen
      thousand homogeneity-checked test materials were issued, covering a very wide
      range of analytes, including pesticides, toxins, veterinary drug residues, trace
      and nutritional elements, food colors, preservatives, sweeteners, alcohol
      congeners, fatty acids, nitrate, and proximate analysis. Participants returned
      85% of requested data, and 47,000 z-score proficiency assessments were made, of
      which 81% were satisfactory. Evidence is presented of improvements in overall
      analytical ability with increased participation in proficiency testing in the
      areas of proximate analysis; organochlorine pesticide analysis; and lead,
      mercury, and acesulfame-K analyses. Little improvement was shown in other
      analytical areas such as calcium analysis. Overall accuracies for analysis of
      specific pesticides and specific trace elements in the circulated test materials
      were compared.

PMID- 9241852
TI  - Predictive microbiology of dairy products: influence of biological factors
      affecting growth of Listeria monocytogenes.
AB  - The growth potential of Listeria monocytogenes was evaluated at low temperature
      in sterilized milk and raw dairy products. Sterilized and raw milk were
      inoculated with different strains of L. monocytogenes in 2 physiological states
      and at various contamination levels. Raw cheese was naturally contaminated with
      Listeria spp. The results suggest that some biological factors influence the
      growth capacity of L monocytogenes in dairy products. Significant strain effect
      was observed at low temperature whatever the growth medium. By contrast, no
      inoculum effect was observed in the 3 dairy products. In raw matrixes, growth of
      L. monocytogenes was influenced greatly by bacterial interactions and
      physiological state of inoculum cells.

PMID- 9241853
TI  - Use of the Microwave-Assisted Process in extraction of fat from meat, dairy, and
      egg products under atmospheric pressure conditions.
AB  - Fat from meat, dairy, and egg products was extracted by using Microwave-Assisted
      Process (MAP) technology under atmospheric pressure conditions. Fat content was
      determined gravimetrically after extraction with microwaves and organic solvents
      that are transparent to microwaves relative to the sample. (In situ hydrolysis
      was performed for dairy and egg products.) Fat from the food sample migrated
      completely to the extractant when samples were irradiated with focused microwave
      for a total of 3 min for meat products, 1 min for dairy products, and 4 min for
      egg products. Unlike current methods used for determining fat in meat products,
      the microwave-assisted method does not require a dry sample, because moisture in
      the sample (around 75%) enhances the efficiency of extraction. No preprocessing
      was required for meat samples other than homogenization, which is critical, as it
      is for other current methods. In addition to speed and ease of use, the features
      of this technology are low solvent consumption, low energy consumption,
      reproducibility, and recoveries similar to or even better than those of
      conventional extraction methods.

PMID- 9241854
TI  - Rapid and alternative screening methods for microbiological analysis.
AB  - Automated analytical instruments for enumerating indicator organisms and
      diagnostic test kits for pathogens can be used in food microbiology to screen
      samples and to replace conventional cultural and confirmation steps. Such methods
      are now available for rapid detection or estimation of groups of (indicator)
      organisms, pathogenic micro-organisms, bacterial toxins and mycotoxins, and
      molds. These alternative methods can be classified by the principles on which
      they are based: modified conventional methods, instrumental measurement of
      bacterial metabolism, bioluminescence, immunological techniques, DNA techniques,
      and combinations of these techniques. To meet user expectations, test kits must
      be accurate, sensitive, specific, rapid (24 h or less), easy to use, and labor
      saving. They must also offer the possibility of computerization, a low detection
      limit, and low investment and running costs. The paper compares the ability of
      alternative methods to meet these criteria. Variations were found, depending on
      the techniques used and the target organism of the analysis. Economic reasons can
      determine whether alternative methods can be used routinely. Adoption of these
      screening systems also can be hampered by lack of internationally coordinated and
      accepted validation protocols.

PMID- 9241855
TI  - Profile and flight time analysis of bovine insulin clusters as a probe of matrix
      assisted laser desorption/ionization ion formation dynamics.
AB  - Detailed ion signal profile and flight time analyses were performed on the time
      of-flight signals obtained for bovine insulin cluster ions produced by matrix
      assisted laser desorption/ionization (MALDI). Profile analyses of the ion signals
      strongly suggest that the signals are made up of a composite of two separate
      components and analysis of the flight times of the two components suggests that
      the ions are formed with different dynamics. The formation dynamics of one
      component of the ions is best described as prompt ionization to yield ions with
      essentially mass-independent total energies. The formation dynamics of the second
      component of the ions is best described as delayed gas-phase ionization of
      entrained material moving at a constant velocity. This model is supported by
      several ancillary experiments and suggests new insights into the mechanism of
      MALDI ion formation.

PMID- 9241858
TI  - Quantification of glycated hemoglobin by electrospray ionization mass
      spectrometry.
AB  - Glycated hemoglobin, considered to be the best index for the treatment of
      diabetes mellitus, was measured by electrospray ionization mass spectrometry
      (ESI/MS) according to the method proposed by Morris et al. at the 44th ASMS
      Conference on Mass Spectrometry and Allied Topics, 1996. They compared the values
      obtained by MS and affinity chromatography. Here, the values obtained by ESI/MS
      were compared with those obtained by high-performance liquid chromatography and
      by latex agglutination immunoassay. Whole blood samples were diluted 500 fold
      with 0.2% formic acid-50% acetonitrile solution and 5 microliters of the diluted
      solution was injected with the ESI/MS system (TSQ 7000) via a sample loop. The
      within-run and between-run relative standard deviations of the ratio of glycated
      and non-glycated beta-chain were less than 5%. The correlation coefficients
      between ESI/MS and conventional methods were higher than 0.96. However,
      considerable discrepancies were observed among methods. ESI/MS will allow
      reproducible measurements of glycated hemoglobin and will be useful in the
      quality control of HbA1c measurement by other principles and also in routine
      clinical laboratory tests.

PMID- 9241856
TI  - Quantitative determination of Orlistat (tetrahydrolipostatin, Ro 18-0647) in
      human plasma by high-performance liquid chromatography coupled with ion spray
      tandem mass spectrometry.
AB  - A rapid, sensitive and specific analytical method was developed and validated to
      quantify tetrahydrolipostatin (Orlistat, Ro 18-0647) in human plasma in order to
      provide pharmacokinetic data from clinical trials. This method employs a
      preliminary plasma protein precipitation step followed by a simple, one-step
      liquid-liquid extraction procedure to isolate Ro 18-0647 and its pentadeuterated
      internal standard, Ro 18-0647-d5, from the biological matrix. Reconstituted
      extracts were analyzed by liquid chromatography/ion spray tandem mass
      spectrometry (LC/MS/MS) in the selected reaction monitoring (SRM) mode.
      Chromatography was carried out using a 2 mm i.d. x 50 mm Deltabond Phenyl column.
      The eluent was acetonitrile-2 mM ammonium acetate (90:10). The retention time of
      the analyte was 1.2 min and chromatographic run times were less than 1.5 min. No
      interferences from anticoagulants, collection devices or endogenous constituents
      of the plasma were observed. The assay has a lower limit of quantitation (LLQ) of
      0.20 ng ml-1 in plasma and a lower limit of detection (LLD) of 0.10 ng ml-1
      plasma, based on 1 ml aliquots. The capability to detect 0.025 ng ml-1 in plasma
      has also been demonstrated. The calibration graphs were linear from 0.20 to 10 ng
      ml-1. The assay was initially validated with a linear range of 0.20-1.0 ng ml-1.
      This range was later extended and validated to an upper level of quantitation of
      10 ng ml-1. Intra- and inter-assay precision studies showed a mean variability of
      less than 10%. The recovery, inter-assay precision and accuracy of the method
      were within acceptable bioanalytical standards. The assay has been shown to
      reliably provide automated, unattended sample analysis for approximately 150
      samples per day. In an additional series of tests, Ro 18-0467 was shown to be
      stable under conditions that might be encountered during the analysis of samples
      from clinical trials. This LC/MS/MS assay procedure for Ro 18-0647 in human
      plasma has proven to be robust, sensitive, specific, accurate and reproducible.
      This method has been used to analyze over 5000 study samples.

PMID- 9241857
TI  - Polysulfated carbohydrates analyzed as ion-paired complexes with basic peptides
      and proteins using electrospray negative ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry was used in the negative ion mode to
      analyze complexes of sucrose octasulfate, sucrose heptasulfate and sulfated alpha
      , beta- and gamma-cyclodextrins with synthetically prepared basic peptides, the
      basic protein ubiquitin and polyamines. The spectra presented demonstrate that
      complexes with these basic molecules facilitate the analysis of these
      polysulfated oligosaccharides. Stable (1:1) complexes result from the ion pairing
      between the protonated basic arginine and lysine residues of the peptide and the
      anionic sulfate groups of the polysulfated oligosaccharides. Fragmentation of the
      polysulfated oligosaccharides resulting in the loss of SO3 could be suppressed by
      controlling the experimental conditions, such as the nozzle-skimmer voltage, used
      to obtain the spectra. In the absence of fragmentation, it was possible to obtain
      data on the purity of sucrose octasulfate and sucrose heptasulfate as well as the
      distribution of the sulfated cyclodextrins. The confounding presence of sodium
      counter-ions is also eliminated using this method. Complete chemical sulfation of
      oligosaccharides is difficult to achieve. Thus, data on sample purity are
      essential for the characterization of sulfated oligosaccharides used as
      pharmaceutical agents.

PMID- 9241859
TI  - Ion trap high-performance liquid chromatography/multiple mass spectrometry in the
      determination of beta-agonists in bovine urines.

PMID- 9241860
TI  - Increasing the variability of response sequences in pigeons by adjusting the
      frequency of switching between two keys.
AB  - Three experiments compared the amounts of behavioral variability generated with
      two reinforcement rules. In Experiments 1 and 2 pigeons received food whenever
      they generated a sequence of eight pecks, distributed over two keys, provided
      that the sequence contained a certain number of change-overs between the keys.
      Although no variability was required-the birds could obtain all reinforcers by
      repeating the same sequence-the pigeons emitted a large number of different
      sequences. In Experiment 3 pigeons received food whenever they generated a
      sequence that had not occurred during the last 25 trials. After prolonged
      training, the birds showed more sequence variability than in the first two
      experiments. The analysis of the internal structure of the response sequences
      revealed that, in general, (a) the location of the first peck was highly
      stereotyped; (b) as the trial advanced, the probability of switching to the
      initially preferred key decreased whereas the probability of switching to the
      other key increased; and (c) a first-order Markov chain model with transition
      probabilities given by a logistic function accounted well for the internal
      structure of the birds' response sequences. These findings suggest that, to a
      large extent, the variability of response sequences is an indirect effect of
      adjustments in changeover frequency.

PMID- 9241862
TI  - Food and amphetamine self-administration by baboons: effects of alternatives.
AB  - The effects of the availability of an alternative reinforcer on responding
      maintained by food pellets or fluid solutions were examined in 6 adult male
      baboons (Papio cynocephalus anubis). During daily 23-hr experimental sessions,
      baboons had concurrent access to both food pellets and fluid, with responding
      maintained under fixed-ratio schedules of reinforcement that varied between the
      two commodities. The fixed-ratio requirement, or cost, for pellets was increased
      when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.002 mg/kg d-amphetamine,
      or (d) 0.004 mg/kg d-amphetamine was available. When given nonrestricted
      concurrent access to food pellets and amphetamine at minimal cost (FR 2), baboons
      self-administered sufficient amphetamine to decrease pellet intake. Increasing
      the response requirement for pellets decreased pellet intake at a similar rate
      regardless of the available fluid and increased fluid intake in a variable manner
      among baboons such that there were no statistically significant increases in
      fluid intake. In contrast, when access to pellets was restricted to 70% of
      maximal intake under nonrestricted conditions, increasing pellet cost decreased
      pellet intake and increased fluid intake more rapidly when the high amphetamine
      dose was available. Thus, amphetamine was more effective as an economic
      substitute for pellets when access to pellets was restricted. The response cost
      for vehicle and both amphetamine concentrations was increased when baboons had
      nonrestricted and restricted access to pellets. Increasing the response
      requirement for fluid delivery decreased intake of all three fluids similarly
      under both pellet-access conditions. The results indicate that substitution
      between commodities with minimal commonalities can be studied under controlled
      laboratory conditions and is dependent upon reinforcement schedule and commodity
      restrictions.

PMID- 9241863
TI  - Predicting the extension of equivalence classes from primary generalization
      gradients: the merger of equivalence classes and perceptual classes.
AB  - In Experiment 1, 6 college students were given generalization tests using 25 line
      lengths as samples with a long line, a short line, and a "neither" option as
      comparisons. The neither option was to be used if a sample did not go with the
      other comparisons. Then, four-member equivalence classes were formed. Class 1
      included three nonsense words and the short line. Class 2 included three other
      nonsense words and the long line. After repeating the generalization test for
      line length, additional tests were conducted using members of the equivalence
      classes (i.e., nonsense words and lines) as comparisons and intermediate-length
      lines as samples. All Class 2 comparisons were selected in the presence of the
      test lines that also evoked the selection of the long line in the generalization
      test that had been given before equivalence class formation. Class 1 yielded
      complementary findings. Thus, the preclass primary generalization gradient
      predicted which test lines acted as members of each equivalence class. Regardless
      of using comparisons that were nonsense words or lines, the post-class-formation
      gradients overlapped, showing the substitutability of class members. Experiment 2
      assessed the discriminability of the intermediate-length test lines from the
      Class 1 (shortest) and Class 2 (longest) lines. The test lines that functioned as
      members of an equivalence class were discriminable from the line that was a
      member of the same class by training. Thus, these test lines also acted as
      members of a dimensionally defined class of "long" or "short" lines. Extension of
      an equivalence class, then, involved its merger with a dimensionally defined
      class, which converted a close-ended class to an open-ended class. These data
      suggest a means of predicting class membership in naturally occurring categories.

PMID- 9241866
TI  - Modeling the environmental fate of atrazine.
AB  - Mathematical simulation models of fate and transport of chemicals have been
      identified by researchers and regulators as potentially valuable tools for
      improving the understanding of the environmental behavior of chemicals which may
      be released to the environment as a consequence of routine (i.e., normal
      manufacturing, use, disposal) and non-routine (e.g., accidental spillage) events.
      In this context, CHEMFRANCE, a regional fugacity model level III, which
      calculates the environmental distribution of organic chemicals in 12 defined
      regions of France, or France as a whole, has been designed. The aim of this study
      is to show that CHEMFRANCE provides valuable simulation results for understanding
      the environmental fate behavior of atrazine.

PMID- 9241865
TI  - Evaluation of critical body residue QSARs for predicting organic chemical
      toxicity to aquatic organisms.
AB  - The critical body residue (CBR) is the concentration of chemical bioaccumulated
      in an aquatic organism that corresponds to a defined measure of toxicity (e.g.,
      mortality). The CBR can provide an alternative measure of toxicity to traditional
      waterborne concentration measurements (e.g., concentration in water causing 50%
      mortality). The CBR has been suggested as a better estimator of dose than the
      external water concentration and has been postulated to be constant for chemicals
      with the same mode of action. CBR QSARs have both theoretical and experimental
      support, developed primarily from studies on the acute toxicity of narcotic
      chemicals to small fish. CBR QSARs are less well developed for the aquatic
      toxicity of non-narcotic chemicals. CBRs vary substantially with the mode of
      action and toxicity endpoint, and may be affected by genetic, hormonal or
      environmental variation. CBR QSARs may not be applicable to very hydrophobic
      chemicals, chemicals with specific modes of action, or those with toxicity
      controlled by kinetic processes such as biotransformation. CBRs models have not
      been developed or evaluated for sediment and dietary exposure routes. Application
      of CBR QSARs to contaminated site assessments will require further research and
      development.

PMID- 9241864
TI  - Behavior of rats under fixed consecutive number schedules: effects of drugs of
      abuse.
AB  - Four rats responded under a simple fixed consecutive number schedule in which
      eight or more consecutive responses on the run lever, followed by a single
      response on the reinforcement lever, produced the food reinforcer. Under this
      simple schedule, dose-response curves were determined for diazepam, morphine,
      pentobarbital, and phencyclidine. The rats were then trained to respond under a
      multiple fixed consecutive number schedule in which a discriminative stimulus
      signaled when the response requirement on the run lever had been completed in one
      of the two fixed consecutive number component schedules. Under control
      conditions, the percentage of reinforced runs under the multiple-schedule
      component with the discriminative stimulus added was much higher than the
      percentage of reinforced runs under the multiple-schedule component without the
      discriminative stimulus. All of the drugs decreased the percentage of reinforced
      runs under each of the fixed consecutive number schedules by increasing the
      conditional probability of short run lengths. This effect was most consistently
      produced by morphine. The drugs produced few differences in responding between
      the multiple fixed consecutive number components. Responding under the simple
      fixed consecutive number schedule, however, was affected at lower doses of the
      drugs than was responding under the same fixed consecutive number schedule when
      it was a component of the multiple schedule. This result may be due to the
      difference in schedule context or, perhaps, to the order of the experiments.

PMID- 9241868
TI  - Environmental contamination and human exposure assessment to manganese in the St
      Lawrence River ecozone (Quebec, Canada) using an environmental fate/exposure
      model: GEOTOX.
AB  - Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic derivative of
      manganese (Mn) used as an additive in unleaded gasoline. The combustion of MMT
      leads to the formation of oxides of manganese. The objective of the present study
      is to predict the environmental levels of Mn and the human exposure in the St
      Lawrence ecozone (fluvial section, Quebec, Canada) using an environmental
      fate/exposure model: GEOTOX. The results of our MMT research program on abiotic
      and biotic components of the ecosystem and on the human exposure were used to
      validate the model estimations. Air and surface soil were selected as source
      terms with an annual Mn input rate in each compartment of 0.083-0.113 mol km-2 d
      1 and 0.44-0.87 mol km-2 d-1 respectively (Mn3O4 equivalent). The predicted air,
      soil, plant, surface water and sediment concentrations were similar (+/- 50%) to
      values measured in the Montreal region. As expected, the ingestion pathway was
      the main absorption route for adults (> 99%), with vegetables and fruits
      contributing almost 80% of the dietary intake of Mn. The multimedia exposure
      doses for adult men predicted by the model ranged between 0.04 and 0.08 mg kg-1 d
      1 compared to 0.004 and 0.201 mg kg-1 d-1 (average = 0.05) for workers from the
      MMT study. Considering the landscape configuration and the source vectors (air
      and soil) included in the model, GEOTOX estimations were in good agreement with
      measured values.

PMID- 9241867
TI  - Health risk assessment of an industrial site contaminated with polycyclic
      aromatic hydrocarbons using CalTOX, an environmental fate/exposure model.
AB  - This paper presents the results of a risk assessment study made using CalTOX, a
      multimedia, multiple pathway risk assessment model. The case study is based on
      the Polycyclic Aromatic Hydrocarbon (PAH) soil contamination resulting from the
      activities of a natural gas power station over a period of 70 years. It describes
      model characteristics and input parameters such as physico-chemical properties,
      landscape description, and human exposure factors. Model simulations and risk
      estimations corresponding to different remedial scenarios in an industrial zone
      are also presented. These estimations were based on soil contamination by 16 PAHs
      in the root-zone and vadose-zone layer. Results show that adult exposure
      (workers) to contaminated soil will lead to a potential health risk of
      carcinogenic effects, and to no potential risk of non-carcinogenic effects. On
      the other hand, the addition of 10 cm of clean soil over the contaminated soil
      (mitigated scenario) decreases the lifetime cancer risk to an acceptable level.
      The sensitivity analysis showed that the half-life of benzo[a]pyrene in the root
      zone soil is the most sensitive parameter and that it contributes significantly
      to the variability of the cancer risk estimation. In addition, the cancer risk
      level of the workers exposed to this substance, as estimated by CalTOX (point
      estimate) in the mitigated and unmitigated scenario, corresponds approximately to
      the 95th percentile value obtained by means of Monte-Carlo simulations. Finally,
      CalTOX has proven to be a valuable tool to predict and elaborate scenarios for
      the risk management of sites contaminated as a result of industrial activities.

PMID- 9241869
TI  - Occupational exposure modelling with ease.
AB  - This article presents a validation exercise performed from eight practical case
      studies on EASE (version 2.0), a knowledge-based system allowing to estimate the
      workplace exposure to chemicals. Our results show that EASE represents a valuable
      simulation tool in occupational hygiene. However, it requires to be refined and
      extended to more realistic and precise situations to be easily used in practice.

PMID- 9241870
TI  - Chemical composition of sediments, suspended matter, river water and ground water
      of the Nile (Aswan-Sohag traverse).
AB  - Sediment, suspended matter, river water and ground water samples were collected
      at twelve sites in the drainage valley of the Nile River, around Sohag (Central
      Egypt) and close to the Aswan High Dam. Elemental composition of the river water
      (27 elements), ground water (eight elements), suspended matter (12 elements) and
      sediments (12 elements) was studied. Aswan High Dam construction, agricultural
      and industrial human activities have led to dramatic changes in the Nile River
      chemistry. Nowadays, the Nile River has the highest dissolved salt content among
      the major African rivers. Dissolved transport is a major process for Ca, K, Sr,
      Zn, Cu, Ni and V. Manganese, Fe and Cr are mainly carried by suspended matter.
      The Nile suspended matter is exhausted in almost all elements studied (except for
      Mn) compared to the world average river suspended matter. Along the course of the
      river, the distribution of elements in the suspended matter and sediments is
      generally controlled by natural processes: the relative importance of elemental
      transport phases; and the oxidation, precipitation and sedimentation of mineral
      species through the varying physico-chemical conditions of the environment.
      Pollution input in the Nile particulate load is not major, as compared to the
      natural inputs. Eight genetic particle types describe the composition of the Nile
      suspended matter and sediments: (1) biogenous-aeolian (or silica); (2)
      terrigenous (Fe-aluminosilicate); (3) authigenic (calcium carbonate); (4)
      biogenous (apatite); (5) authigenous-terrigenous (Fe-oxyhydroxide
      montmorillonite); (6) diagenetic (iron-sulfide); (7) terrigenous (titanium
      oxide); (8) authigenous (Mn-Fe-oxyhydroxide).

PMID- 9241871
TI  - Heavy metal contamination in freshwater fish from the border region between
      Norway and Russia.
AB  - The contents of Cd, Cu, Cr, Hg, Ni and Zn in muscle, liver and gills were studied
      in whitefish, perch, pike, brown trout, burbot and vendace from three lake
      localities in a watercourse in the border region between Norway and Russia, in
      the vicinity of mining activity and several metallurgic smelters. The contents of
      Cd and Ni in fish tissue increased with increasing proximity to the smelters,
      whereas the other elements showed similar concentrations at the three localities.
      The recorded heavy metal concentrations appeared to be within the ranges reported
      for fish from other metal-contaminated lakes, and higher than comparable
      observations from unpolluted systems. The heavy metal concentrations were usually
      lowest in muscle and highest in the liver or the gills. Significant differences
      in metal concentration levels were found between different fish species, but Hg
      was the only metal where these species differences were possibly related to
      biomagnification. For the other elements, the concentrations generally appeared
      to be inversely related to the trophic level of the fish species.

PMID- 9241872
TI  - An assessment of heavy metals and boron contamination in workplace atmospheres
      from ceramic factories.
AB  - The occupational exposure in workplace atmospheres of ceramic factories to some
      metals (Ba, Cd, Co, Cr, Cu, Ni, Zn) and boron has been studied. During 1994
      samples were collected at several ceramic factories from the Comunitat Valenciana
      (Spain) in a random fashion to avoid correlation problems regarding data
      analysis; factories were sampled to provide a representative cross-section.
      Powdered samples were treated with concentrated nitric acid according to the
      National Institute for Occupational Safety and Health (NIOSH) digestion procedure
      for the analysis of metals in air samples. Heavy metals were analyzed by AAS and
      boron by UV/Visible spectrophotometry using the Azomethine-H method.
      Concentrations found for Cd, Cr, Cu, Ni and Zn were considered very low in the
      environment of this industrial sector. However, Co, Ba and B were detected in
      several samples with concentrations above the threshold limit value (TLV),
      referred to airborne concentrations of substances in workplace atmospheres.
      Principal component analysis (PCA) has also been carried out in order to classify
      the workplaces studied and their potential hazard to the workers.

PMID- 9241873
TI  - Variations in the concentration of plutonium, strontium-90 and total alpha
      emitters in human teeth collected within the British Isles.
AB  - Concentrations of plutonium-239, plutonium-240, strontium-90 and total alpha
      emitters have been measured in children's teeth collected throughout Great
      Britain and Ireland. The concentrations of plutonium and strontium-90 were
      measured in batched samples, each containing approximately 50 teeth, using low
      background radiochemical methods. The concentrations of total alpha-emitters were
      determined in single teeth using alpha-sensitive plastic track detectors. The
      results showed that the average concentrations of total alpha-emitters and
      strontium-90 were approximately one to three orders of magnitude greater than the
      equivalent concentrations of plutonium-239,240. Regression analyses indicated
      that the concentrations of plutonium, but not strontium-90 or total alpha
      emitters, decreased with increasing distance from the Sellafield nuclear fuel
      reprocessing plant-suggesting that this plant is a source of plutonium
      contamination in the wider population of the British Isles. Nevertheless, the
      measured absolute concentrations of plutonium (mean = 5 +/- 4 mBq kg-1 ash wt.)
      were so low that they are considered to present an insignificant radiological
      hazard.

PMID- 9241874
TI  - The trophodynamics of PCBs, including mono- and non-ortho congeners, in the food
      web of North-Central Lake Ontario.
AB  - The distribution of polychlorinated biphenyls (PCBs) in the food-web of Lake
      Ontario was studied to determine the parameters that control the trophodynamics
      of PCB congeners; including toxic non-ortho and mono-ortho PCBs.
      'Biomagnification' of PCBs was evident in the food-web as total PCBs increased
      through trophic levels when concentrations were calculated on both a wet wt. and
      lipid weight basis; although there was no evidence of biomagnification between
      forage fish and piscivorous fish. Biomagnification was greatest for congeners
      with log octanol-water partition (log Kow) coefficients between 6 and 7.5. Non
      ortho congeners 77 and 126, and congener 151 were not biomagnified to the extent
      of other congeners with similar Kow, which was attributed to high rates of
      metabolic clearance of these compounds. The Toxic Equivalent Quantities (TEQs)
      associated with non-ortho and mono-ortho PCBs increased throughout the Lake
      Ontario food-web. The high TEQ observed in herring gull eggs was primarily the
      result of very high concentrations of congener 126 in this component of the food
      web.

PMID- 9241875
TI  - Sorption/desorption of radioactive contaminants by sediment from the Kara Sea.
AB  - To understand the long term impact of the disposal of radioactive waste on the
      Kara Sea, partition coefficients (Kd) for several important radionuclides, the
      mineralogy of the sediment, and the relationship of Kd to liquid-to-solid ratio
      were quantified. Sediment was obtained from four locations in the Kara Sea area.
      Slow sorption kinetics were observed for 85Sr, 232U, 125I and 99Tc, whilst
      sorption was rapid (less than 50 h to steady-state) for 137Cs, 210Pb, and 241Am.
      Partition coefficients (Kd) were determined using batch type experiments and
      sorption isotherms which were developed for 85Sr, 99Tc, 125I, U and 137Cs.
      Partition coefficients for 137Cs were approx. 350 ml/g for sediment from the
      Trough and 180 ml/g for Stepovogo Fjord. This difference may be caused by the
      lower fraction of expandable clay in sediment from the fjord. Uptake of 85Sr,
      99Tc, 125I, and U were all similar for both locations, with Kd values averaging
      4, 3, 17 and 60 ml/g, respectively. The Kd for 137 Cs varied non-linearly from 40
      to 3800 ml/g as the liquid-to-solid ratio varied from 3.4 to 6500, but only when
      the sorption capacity was high compared to the mass of 137Cs in the closed system
      of the experiment. Under identical conditions, sediment with lower Kd values
      showed no effect. Oxidation of sediment effectively desorbed 99Tc from the solid
      phase, whilst it caused increased uptake of 85Sr and U. In sequential rinses with
      fresh seawater, desorption was limited to 60% of 137Cs and 85Sr, and 35% of
      uranium.

PMID- 9241876
TI  - The history and source of particulate 137Cs and 239,240Pu deposition in sediments
      of the Ob River Delta, Siberia.
AB  - This paper presents the first results of a project designed to examine the
      transfer of particle-associated artificial radionuclides down the Ob River in
      Siberia to its delta over the past 5 decades. The main sources include fallout
      from atmospheric nuclear weapons tests and weapons complexes and test sites of
      the Former Soviet Union in or near the Ob watershed. The approach is to measure
      the accumulation of the radionuclides in undisturbed delta sediments-obtaining a
      record of their deposition over time. These records were found in sediments of
      shallow lakes apart from, and connected to, the main channel. Sediment cores were
      collected in the summer of 1994 using a shallow draft catamaran to reach these
      lakes from a support ship in the main channel. Measurements are presented on the
      depth distributions of 137Cs and Pu isotopes and their inventories in a series of
      dated sediment cores-including one from a location in the Taz Estuary (which does
      not receive Ob River sediments). Sediment dating was carried out using the excess
      210Pb technique. The results obtained are compared with known information on the
      temporal history of releases from the various sources and characteristics of the
      isotopic composition of the sources. The results show that good records of
      radionuclide deposition indicate that the major fraction of 137Cs and Pu isotopes
      deposited in these delta sediments comes from atmospheric nuclear weapons test
      fallout-both delivered directly from the atmosphere and from downstream transport
      of watershed sediments. No more than 25% of the observed inventories could be
      derived from other sources.

PMID- 9241877
TI  - Current and potential doses from Arctic seafood consumption.
AB  - Current collective and individual dose rates to humans are estimated from the
      consumption of seafood harvested in the Arctic Seas. Statistical data on catches
      are used for the dose assessment, as well as observed data (1991-1994) on the
      radioactivity of marine biota. The actual collective dose rates to the world
      population are estimated to be: 2.7-4.5 manSv/year due to consumption of seafood
      from the Barents Sea, and 0.03 manSv/year-due to seafood from the Kara Sea. The
      contribution of 137Cs to the collective dose rate is about 90%. Current
      individual dose rates to high-rate consumers are estimated to be: 2.6 x 10(-6)
      Sv/year due to seafood from the Barents Sea; and 4.2 x 10(-6) Sv/year-due to
      seafood from the Kara Sea. The future radiological impact of the radioactive
      waste (RW) disposals in the Kara Sea is simulated for the period over 1000 years,
      using the regional box model of the Arctic Seas. The model predictions are made
      for three hypothetical scenarios of long-term radionuclide releases, prepared
      within the framework of the International Arctic Seas Assessment Project. The
      potential collective dose to world population truncated to 3000 AD is shown to be
      not higher than 0.13 manSv. The maximum individual dose rates from Arctic seafood
      consumption are estimated to be about 1.2 x 10(-7) Sv/year. The predicted doses
      are much smaller than the actual doses due to the current radioactive
      contamination of the Arctic Seas.

PMID- 9241878
TI  - The sunken nuclear submarine Komsomolets and its effects on the environment.
AB  - This paper discusses the possible release mechanisms for radionuclides on board
      the sunken nuclear submarine Komsomolets. With an aim to determine whether or not
      the sunken submarine presents any significant hazards to man, a worst-case
      approach is taken in estimating the environmental effects of the released
      radionuclides. It is found that neither the submarine hull nor the reactor vessel
      will be destroyed by corrosion for at least 1000 years. While the total
      radionuclide inventory presently is estimated to be approx. 8 PBq, only approx. 1
      TBq is released annually into the surrounding environment. The distribution of
      the released radionuclides in the ocean has been modeled, and it was found that
      not even in the most heavily affected waters will the present contamination
      levels change significantly due to the Komsomolets. In short, this study, which
      does not pretend to completely answer all environmental questions related to the
      sunken submarine, clearly indicates that the Komsomolets represents no
      significant hazard to man, today or in the future.

PMID- 9241879
TI  - Plutonium in fish, algae, and sediments in the Barents, Petshora and Kara Seas.
AB  - This work contributed to a joint research programme between the Finnish Centre
      for Radiation and Nuclear Safety and the Murmansk Marine Biological Institute in
      the Arctic. Radioanalyses for plutonium isotopes were performed on more than 50
      sediment samples, 12 algae samples and 19 fish samples. Plutonium concentrations
      in algae and fish samples, including fish meat, bone and liver, were low or in
      many cases below detection limits. Some differences in plutonium concentrations
      of sediments were found between different sampling areas. However, the
      concentrations were low. The Pu isotopic ratios were similar to those found in
      environmental samples generally when Pu is derived from global fallout or
      discharges from reprocessing plants. No local enhancement of plutonium
      contamination was found in the marine areas studied. However, the sampling
      locations represent only areas of free access; prohibited military areas of North
      west Russia with potential pollution sources were not included.

PMID- 9241880
TI  - Sea-ice production and transport of pollutants in the Laptev Sea, 1979-1993.
AB  - Pollutants such as radionuclides can be incorporated into ice formed in shallow
      waters of the marginal seas, by suspension freezing, including frazil- and anchor
      ice formation. This ice thickens through the winter and can survive the summer
      melt to eventually be pushed into the perennial ice zone and thus be transported
      long distances. After a few years, when the ice finally melts, these
      radionuclides can be re-released in biologically rich waters. We estimate that a
      mean of 256,000 km2 of sea ice is produced annually in the shallow water area of
      the Laptev Sea during the October freeze-up and in the flaw lead during winter,
      accounting for approx. 20% of the total ice area fluxing through the Fram Strait
      per year.

PMID- 9241881
TI  - Potential for rapid transport of contaminants from the Kara Sea.
AB  - Export of sea ice from the Kara Sea may redistribute contaminants entrained from
      atmospheric, marine and riverine sources. Ice exiting the Kara Sea ice to the
      north, will influence the Fram Strait, Svalbard and Barents Sea regions. Kara Sea
      ice may also be exported to the Barents Sea through straits north and south of
      Novaya Zemlya. Some ice from the Kara Sea makes its way into the Laptev Sea to
      the north and south of Severnaya Zemlya. Data on ice exchange and contaminant
      levels are not adequate to assess contaminant flux.

PMID- 9241882
TI  - Benchmarking of numerical models describing the dispersion of radionuclides in
      the Arctic Seas.
AB  - As part of the International Arctic Seas Assessment Project (IASAP) of the
      International Atomic Energy Agency (IAEA), a working group was created to model
      the dispersal and transfer of radionuclides released from radioactive waste
      disposed of in the Kara Sea. The objectives of this group are: (1) development of
      realistic and reliable assessment models for the dispersal of radioactive
      contaminants both within, and from, the Arctic ocean; and (2) evaluation of the
      contributions of different transfer mechanisms to contaminant dispersal and
      hence, ultimately, to the risks to human health and environment. With regard to
      the first objective, the modelling work has been directed towards assessment of
      model reliability and asone aspect of this, a benchmarking exercise has been
      carried out. This paper briefly describes the benchmark scenario, the models
      developed and used, and discusses some of the benchmarking results. The role of
      the exercise within the modelling programme of IASAP will be discussed and future
      work described.

PMID- 9241883
TI  - Collective doses to man from dumping of radioactive waste in the Arctic Seas.
AB  - A box model for the dispersion of radionuclides in the marine environment
      covering the Arctic Ocean and the North Atlantic Ocean has been constructed.
      Collective doses from ingestion pathways have been calculated from unit releases
      of the radionuclides 3H, 60Co, 63Ni, 90Sr, 129I, 137Cs, 239Pu and 241Am into a
      fjord on the east coast of NovayaZemlya. The results show that doses for the
      shorter-lived radionuclides (e.g. 137Cs) are derived mainly from seafood
      production in the Barents Sea. Doses from the longer-lived radionuclides (e.g.
      239Pu) are delivered through marine produce further away from the Arctic Ocean.
      Collective doses were calculated for two release scenarios, both of which are
      based on information of the dumping of radioactive waste in the Barents and Kara
      Seas by the former Soviet Union and on preliminary information from the
      International Arctic Sea Assessment Programme. A worst-case scenario was assumed
      according to which all radionuclides in liquid and solid radioactive waste were
      available for dispersion in the marine environment at the time of dumping.
      Release of radionuclides from spent nuclear fuel was assumed to take place by
      direct corrosion of the fuel ignoring the barriers that prevent direct contact
      between the fuel and the seawater. The second scenario selected assumed that
      releases of radionuclides from spent nuclear fuel do not occur until after
      failure of the protective barriers. All other liquid and solid radioactive waste
      was assumed to be available for dispersion at the time of discharge in both
      scenarios. The estimated collective dose for the worst-case scenario was about 9
      manSv and that for the second scenario was about 3 manSv. In both cases, 137Cs is
      the radionuclide predicted to dominate the collective doses as well as the peak
      collective dose rates.

PMID- 9241884
TI  - Perturbation in the 240Pu/239Pu global fallout ratio in local sediments following
      the nuclear accidents at Thule (Greenland) and Palomares (Spain).
AB  - It is well established that the main source of the plutonium found in marine
      sediments throughout the Northern Hemisphere is global stratospheric fallout,
      characterized by a typical 240Pu/239Pu atom ratio of approximately 0.18.
      Measurement of perturbations in this ratio at various sites which had been
      subjected to close-in fallout, mainly from surface-based testing (e.g. Bikini
      Atoll, Nevada test site, Mururoa Atoll), has confirmed the feasibility of using
      this ratio to distinguish plutonium from different fallout sources. In the
      present study, the 240Pu/239Pu ratio has been examined in samples of sediment
      (and soil) collected at Thule (Greenland) and Palomares (Spain), where accidents
      involving the release and dispersion of plutonium from fractured nuclear weapons
      occurred in 1968 and 1966, respectively. The 240Pu/239Pu ratio was measured by
      high-resolution alpha spectrometry and spectral deconvolution, and confirmed in
      the case of the most active samples by high-resolution X-ray spectrometry. Only
      samples which displayed plutonium heterogeneities, i.e. hot particles or
      concentrations well in excess (at least two orders of magnitude) of those
      expected from global fallout, were selected for analysis. The analytical results
      showed that at Thule the mean 240Pu/239Pu atom ratio was 0.033 +/- 0.004 (n = 4),
      while at Palomares the equivalent ratio appeared to be significantly higher at
      0.056 +/- 0.003 (n = 4). Both ratios are indicative of low burn-up plutonium and
      are consistent with those reported for weapons-grade plutonium. It is noteworthy
      that the mean 238Pu/239Pu activity ratio in the Thule samples, at 0.0150 +/-
      0.0017 (n = 4), was also lower than that measured in the Palomares samples,
      namely, 0.0275 +/- 0.0012 (n = 4). The 241Pu/239Pu ratios were similarly
      different. Finally, the data show, in contrast to Palomares, that not all of the
      samples from the Thule accident site were contaminated with plutonium of
      identical isotopic composition.

PMID- 9241885
TI  - Spatial variation in the vulnerability of Norwegian Arctic counties to
      radiocaesium deposition.
AB  - Under the Arctic Monitoring and Assessment Programme (AMAP), studies have been
      undertaken to compare potential fluxes of radiocaesium via important food
      products. The results for three Norwegian Arctic counties are presented in this
      paper. The comparative importance of different foodstuffs in contributing to
      collective dose varies spatially due to differing rates of production and
      transfer. Although reindeer meat is an important contributor to the radiocaesium
      flux following a nuclear release, other food products such as cow milk and lamb
      have been identified as potentially important. Assuming an even deposition
      following a nuclear release the radiocaesium flux was estimated to be highest for
      reindeer meat in Finnmark and Troms, whereas cow milk gave the highest flux in
      Nordland. The total number, geographical distribution and diet composition of
      indigenous peoples within different Arctic regions is an important factor
      affecting individual and collective doses arising from a nuclear release.
      Finnmark has been shown to be the most vulnerable of the three counties because
      it has the highest flux of radiocaesium and the largest number of indigenous
      people. The potential contribution of foodstuffs which are known to readily
      accumulate radiocaesium needs further consideration, in particular, mushrooms,
      freshwater fish and berries.

PMID- 9241886
TI  - Radioactive contamination from dumped nuclear waste in the Kara Sea--results from
      the joint Russian-Norwegian expeditions in 1992-1994.
AB  - Russian-Norwegian expeditions to the Kara Sea and to dumping sites in the fjords
      of Novaya Zemlya have taken place annually since 1992. In the fjords, dumped
      objects were localised with sonar and ROV equipped with underwater camera.
      Enhanced levels of 137Cs, 60Co, 90Sr and 239,240Pu in sediments close to dumped
      containers in the Abrosimov and Stepovogo fjords demonstrated that leaching from
      dumped material has taken place. The contamination was inhomogeneously
      distributed and radioactive particles were identified in the upper 10 cm of the
      sediments. 137Cs was strongly associated with sediments, while 90Sr was more
      mobile. The contamination was less pronounced in the areas where objects presumed
      to be reactor compartments were located. The enhanced level of radionuclides
      observed in sediments close to the submarine in Stepovogo fjord in 1993 could,
      however, not be confirmed in 1994. Otherwise, traces of 60Co in sediments were
      observed in the close vicinity of all localised objects. Thus, the general level
      of radionuclides in waters, sediments and biota in the fjords is, somewhat higher
      or similar to that of the open Kara Sea, i.e. significantly lower than in other
      adjacent marine systems (e.g. Irish Sea, Baltic Sea, North Sea). The main sources
      contributing to radioactive contamination were global fallout from atmospheric
      nuclear weapon tests, river transport from Ob and Yenisey, marine transport of
      discharges from Sellafield, UK and fallout from Chernobyl. Thus, the radiological
      impact to man and the arctic environment of the observed leakages from dumped
      radioactive waste today, is considered to be low. Assuming all radionuclides are
      released from the waste, preliminary assessments indicate a collective dose to
      the world population of less than 50 man Sv.

PMID- 9241887
TI  - Radioactive contamination in the environment of the nuclear enterprise 'Mayak'
      PA. Results from the joint Russian-Norwegian field work in 1994.
AB  - A brief overview of the radioactive waste inventory of the 'Mayak' PA
      reprocessing plant, Chelyabinsk Region, Russia is given together with a
      description of the environmental contamination caused by its activities and the
      origins of contamination. The joint Russian-Norwegian field work in 1994 is
      described, together with the major analytical results. The field work was of a
      limited extent, and was not designed to include a complete mapping of the
      environmental contamination around the plant. The results are, however, in good
      agreement with the very extensive previous Russian investigations. The highest
      concentrations of radioactivity were found in Reservoirs 10 and 11 and at the
      floodplain of the upper Techa River (Asanov Swamp). Also high concentrations are
      found in biota, especially fish from Reservoir 10.

PMID- 9241889
TI  - Trends in neonatal exchange transfusions at Yodogawa Christian Hospital.
AB  - A review was conducted to determine the trends in exchange transfusion (ET) of
      newborn infants at the Yodogawa Christian Hospital during the past 18 years. At
      that hospital in 1957, the first ET was performed on a term infant with severe
      hemolytic jaundice caused by rhesus factor (Rh) incompatibility. By 1989, ET had
      been performed in more than 1400 newborn infants. These cases of newborns who had
      had ET were retrospectively reviewed, with a focus on every 3 year period from
      1974 to 1992. The total number of infants requiring ET noticeably decreased from
      68 cases (14.0% of total admissions) in 1974 to 19 cases (6.1% of total
      admissions) in 1992. (chi 2, P < 0.001) There were three major significant
      changes in ET during those years. The first was a change in the subjects for ET.
      The incidence of ET for term infants showed a marked decrease, while the
      incidence of ET for preterm infants, especially for very low birthweight (VLBW)
      infants (< 1500 g), noticeably increased. The second was a change in indications
      for ET. There was a marked decrease in the need for ET as a result of
      hyperbilirubinemia, while the incidence of ET because of other etiologies, such
      as septicemia and/or disseminated intravascular coagulopathy, noticeably
      increased. The third was a change in the technical methods of ET. Now at the
      Yodogawa Christian Hospital, 100% of the infants are given ET with an automated
      peripheral two-site method, instead of the Diamond method. Although ET might
      still be a useful treatment for severe hyperbilirubinemia and other acute
      problems, the total number of ET noticeably decreased in accord with a decrease
      in the number of severe hyperbilirubinemia in term newborns. On the other hand,
      the incidence of ET in preterm infants increased relatively, accompanied by an
      increase in the survival of VLBW infants. The automated two-site method is the
      preferred technique for ET at the Yodogawa Christian Hospital, rather than the
      Diamond method. Further changes in ET might occur in accord with new alternative
      measures in future.

PMID- 9241888
TI  - Fatty acid compositions of colostrum, cord blood, maternal blood and major infant
      formulas in Japan.
AB  - Lipid profiles in colostrum, cord blood, maternal blood and major infant formulas
      in Japan were analyzed. In the first part of the study, colostrum obtained from
      36 normal delivery women and six kinds of infant formulas provided by three major
      milk companies were analyzed for their fatty acid composition using capillary gas
      lipid chromatography. Although enriched with docosahexaenoic acid (DHA), the
      percent composition of DHA in the six infant formulas (0.15-0.21%) was
      significantly lower than that in the colostrum (1.1 +/- 0.54). Arachidonic acid
      (AA) and eicosapentaenoic acid (EPA) were present in the colostrum but not
      detectable in the infant formulas. It is recommended that although the exact
      amount of specific fatty acids needed in the infant diet was not completely
      known, to be as close as possible to natural breast milk, the level of DHA, EPA
      and AA should be raised in the infant formulas. In the second part of the study,
      19 pairs of maternal and cord blood were analyzed for their lipid profile. All
      samples were from normal vaginal delivery. The measurement of cholesterol,
      triglycerides, phospholipids and free fatty acids was performed with commercially
      available enzymatic methods on an automated discrete random access analyzer.
      Total fatty acid was determined as described in the first part of the study. The
      results were analyzed with Spearman's rank correlation coefficient. No
      correlation could be found between maternal and fetal concentrations of
      cholesterol, triglycerides, phospholipids or total fatty acids. Correlation could
      be found in non-esterified fatty acids, in palmitic acids, and oleic acid levels.
      It was concluded that the lipid transport and metabolism in the fetal-placenta
      unit is complex and further delicate investigation is required.

PMID- 9241890
TI  - Development of jaundice in Korean neonates after cesarean section.
AB  - The aim of the project was to determine the physiologic mechanisms of later- and
      higher-peak transitional plasma bilirubin levels in Korean infants. Blood
      carboxyhemoglobin, corrected for inhaled CO (COHbc), as an index of bilirubin
      production, and plasma total bilirubin levels in 40 healthy term Korean infants
      delivered by Cesarean section were measured throughout the first week of life.
      The COHbc levels were significantly higher in the Korean neonates than in
      previously studied Caucasian neonates. Moreover, COHbc levels decreased by 28%
      during the first 7 days of life from 0.85 +/- 0.20 to 0.61 +/- 0.34% (P < 0.025).
      This pattern parallels a 15% decrease in total hemoglobin from 181 +/- 23 to 154
      +/- 53 g/L (P < 0.05). In contrast, plasma bilirubin concentrations more than
      doubled from 80 +/- 32 to 172 +/- 48 mumol/L (4.7 +/- 1.8 to 10.0 +/- 2.8 mg/dL;
      P < 0.001), remaining unchanged between days 4 and 7. Both increased production
      and decreased elimination of bilirubin contribute to physiologic jaundice in
      Korean infants.

PMID- 9241891
TI  - Percutaneous central venous catheterization via the great saphenous vein in
      neonates.
AB  - In 44 neonates (mean birthweight 1207 g and mean gestational age 30.0 weeks),
      very small central venous catheters were percutaneously inserted via the great
      saphenous vein on 46 occasions. Catheter-related complications such as catheter
      blockages in 17 (37%), edema in a unilateral leg in three (6%), and mechanical
      disruption in two (4%) were noted. Although two of the neonates were found to
      have bacteremia and five neonates died, none were catheter related. The optimal
      length of catheter insertion (Y) from the great saphenous vein at the level of
      the medial maleollus to the inferior vena cava at T9 and L3 was calculated by
      regression equations utilizing total body length (X). Radiographs taken with
      extended and flexed leg postures revealed that the catheter tips were retracted
      with extension of the lower extremities and the degree of displacement ranged
      from 1 to 4 (mean 2.7) vertebral levels. Because this movement might cause
      migration into veins that connect to the inferior vena cava, the catheter tip
      should be located between T9 and L3, except at the renal vein junction.
      Percutaneous central venous catheterization via the great saphenous vein is safe
      and useful. Regression equations provided for rapid estimation of the optimal
      length of insertion.

PMID- 9241892
TI  - The changing trend in the pattern of infective etiologies in childhood acute
      lower respiratory tract infection.
AB  - The etiologic agents causing acute lower respiratory tract infection (LRTI) in
      hospitalized children were compared for 1995 and 1988. Between May 1994 to April
      1995, 397 children were admitted to Tan Tock Seng Hospital for acute LRTI
      compared to 240 children in 1988. The following criteria for LRTI were used: (i)
      age less than 12 years with a community-acquired LRTI; (ii) presence of cough or
      fever of less than 2 weeks' duration; and (iii) presence of tachypnea, chest
      retractions or pulmonary infiltrates on chest X-ray. Sputum cultures were
      considered suitable for culture if there were less than 25 epithelial cells per
      low power field. Moraxella catarrhalis was considered only if heavy growth of
      more than 3+ was seen. Etiological agents were found in about 70% of patients in
      both studies. Viruses constituted 41.3% of the etiologic agents in 1995 but
      constituted only 28% in 1988; 36% had a bacterial etiology in 1995 compared to
      15% in 1988. The most common bacteria in 1995 was M. catarrhalis (34.7%) followed
      by non-type B Haemophilus influenzae (33%). In contrast, in 1988, Mycoplasma
      (33%) was the predominant organism followed by H. influenzae (17%) and M.
      catarrhalis (11.4%). The increased incidence of M. catarrhalis could be due to
      antibiotic selection. A mixed viral-bacterial etiology was found in 12.3% of the
      1995 cohort. The majority of the bacteria were positive by sputum cultures; only
      4 (3.3%) had positive blood cultures. No penicillin resistance was detected in
      1988; however, in 1995, penicillin resistance was found in 17% of the
      Streptococcus pneumoniae, 38.5% of H. influenzae and 83% of M. catarrhalis. It
      was also found that 30% of the S. pneumoniae were also resistant to erythromycin,
      and 23% were resistant to sulfamethoxaxole-trimethoprim; 5% of the H. influenzae
      had multiple resistance to erythromycin, sulfamethoxazole-trimethoprim and
      chloramphenicol. Among those patients with antibiotic resistance, 30% had
      received prior antibiotics of which 18% had had two or more antibiotics,
      frequently erythromycin or amoxycillin/ampicillin. Judicious use of antibiotics
      is required to check the rising trend of antibiotic resistance.

PMID- 9241894
TI  - Prevalence of asthma, rhinitis and eczema among schoolchildren in Kelantan,
      Malaysia.
AB  - The prevalence and severity of asthma, rhinitis and eczema in Kelantanese
      schoolchildren were determined as part of an international study of the
      epidemiology of asthma and allergic diseases. The international study of asthma
      and allergies in childhood (ISAAC) written questionnaire was administered to 7055
      schoolchildren from February 1995 to August 1995. The respondents were parents or
      guardians of 5- to 7-year-old children (n = 3939), and schoolchildren aged 12-14
      years (n = 3116). The ISAAC video questionnaire (AVQ3.0) was shown to children
      aged 12-14 years after the written questionnaire. The overall prevalences of
      'ever wheezed' and 'wheezing in last 12 months' were 9.4 and 6.0% respectively.
      The prevalence of 'ever diagnosed with asthma' was 9.4%. Both 'ever wheezed' and
      'wheezing in the last 12 months' were significantly higher in 12- to 14-year-old
      children than in 5- to 7-year-old children, with P values of 0.0006 and 0.014
      respectively. No gender differences in the prevalences were observed. For the
      complete study group, 4.7% of children had sleep disturbed by wheezing but only
      1.1% had a severe attack limiting speech in the preceding 12 months. Sleep
      disturbance was more common in the 12- to 14-year-old children than in 5- to 7
      year-old children (P = 0.006). There was no difference between the age groups for
      severe attacks limiting speech. The overall prevalence of rhinitis and eczema
      symptoms were 27 and 12%, respectively. The prevalence of rhinitis in the 12-14
      year age group (38.2%) was significantly higher (P < 0.0001) than in the 5-7 year
      age group (18.2%). The prevalence of eczema in the 5-7 year age group (13.7%) was
      significantly higher (P = < 0.0001) than in the 12-14 year age group (9.9%).
      These prevalence data are comparable with previous reports in Malaysian children,
      but are considerably lower than those reported for most developed countries.

PMID- 9241893
TI  - Immune response to food antigens: kinetics of food-specific antibodies in the
      normal population.
AB  - The role of food-specific antibodies in the pathogenesis of food allergy is
      controversial. The first step in solving this controversy may be the assessment
      of antibody response to food antigens in the normal population. Most of the
      existing data in this field come from studies that used assays of different
      standards. This study investigated food-specific antibodies in the normal
      population using standardized assays. Normal levels of antibody titers were also
      derived for use as reference. Two hundred and eight individuals from different
      age groups participated. Immunoglobulin G (IgG) antibodies to cow's milk and its
      component proteins, and to hen's egg ovalbumin, IgA and IgM antibodies to beta
      lactoglobulin and ovalbumin were measured by enzyme-linked immunosorbent assay.
      The sepharose-radioallergosorbent test was used to measure IgE antibodies to
      cow's milk and ovalbumin. Titers of IgG antibodies to cow's milk and its
      component proteins revealed an age-related trend, peaking in the 5 months-1 year
      age group and then decreased to negligible values in adults. A similar trend was
      observed with IgG anti-ovalbumin antibodies. Temporal association was less
      evident for antibodies of other classes. Only six subjects had positive IgE
      antibodies to cow's milk, while none had positive IgE anti-ovalbumin antibody.
      The prevalences of IgG antibodies to cow's milk, its component proteins, and
      ovalbumin are influenced by age and feeding habits. Cross-reactivity to related
      food antigens is common. The presence of IgE antibodies to food antigens is not a
      physiological phenomenon.

PMID- 9241896
TI  - Serum zinc, copper, and magnesium levels in obese children.
AB  - Serum zinc, copper and magnesium levels were measured using atomic absorption
      spectrophotometry in 41 obese and 41 healthy (control) children (between 7 and 11
      years of age) who were living in Malatya (Turkey). Serum zinc levels of obese
      children (mean value 102.40 +/- 2.78 micrograms/dL) were found to be
      significantly higher than those of the control group (mean value 80.49 +/- 2.98
      micrograms/dL; P < 0.01). Serum copper concentrations were also found to be
      significantly higher in obese children (mean value 132.34 +/- 1.79 micrograms/dL)
      than the healthy controls (mean value 107.58 +/- 1.62 micrograms/dL; P < 0.01).
      On the other hand, serum magnesium levels were found to be significantly lower in
      obese children (mean value 1.78 +/- 0.03 mg/dL) than in the healthy children
      (mean value 2.14 +/- 0.04 mg/dL; P < 0.01).

PMID- 9241895
TI  - Age-related changes of serum progastrin-releasing peptide levels during
      childhood.
AB  - Gastrin-releasing peptide (GRP) has attracted much attention in recent years
      because it has become recognized as a significant tissue-specific growth factor.
      To investigate the physiological significance of this peptide in growing
      children, the time course of serum ProGRP(31-98) level, a precursor hormone of
      GRP, in children was assessed. A total of 118 serum samples including cord blood
      was examined with informed consent by using a specific enzyme-linked
      immunosorbent assay (ELISA) system to measure serum ProGRP(31-98). The serum
      ProGRP(31-98) level was highest in cord blood and neonatal samples, rapidly
      declined by 1 year of age and then gradually declined to the adult level by 5
      years of age. This time-dependent change of serum ProGRP(31-98) level suggests
      the importance of GRP as a physiological growth factor in fetal and neonatal
      tissues.

PMID- 9241897
TI  - The effects of long-term anticonvulsive treatment on serum lipid profile.
AB  - Serum lipids were determined in 10 untreated patients with recently diagnosed
      epilepsy, 21 patients treated with carbamazepine (CBZ), 10 patients treated with
      valproate (VPA) and in 15 healthy children. In relation to the controls, patients
      receiving CBZ showed increased serum high-density lipoprotein cholesterol (HDLc),
      apolipoprotein A (Apo-A) and apolipoprotein B (Apo-B). Patients receiving VPA
      showed increased Apo-B levels. There were no significant differences in total
      cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLc)
      or very low-density lipoprotein cholesterol (VLDLc) between all groups. The
      changes in lipid metabolism may be associated with the induction of liver enzymes
      during anti-epileptic drug metabolism. The CBZ-induced change in serum lipid
      levels was considered to be a possible factor against atherosclerosis and
      coronary heart disease in epileptic patients.

PMID- 9241898
TI  - Application of nested polymerase chain reaction for the rapid diagnosis of infant
      botulism type B.
AB  - A nested polymerase chain reaction was utilized to successfully detect the type B
      botulinum neurotoxin gene of Clostridium botulinum in feces from a 6-month-old
      patient, who had already been diagnosed with type B infant botulism by mouse bio
      assay. This method of rapid diagnosis without enrichment culture of feces can be
      applied to other types of toxins in the use of the type-specific primers. Further
      investigations, however, are required to define the sensitivity and specificity
      of the method.

PMID- 9241899
TI  - Clinicopathological characteristics of the focal and segmental form of idiopathic
      membranous nephropathy: comparison with the typical form of this disease.
AB  - Although idiopathic membranous nephropathy (IMN) is thought to represent a
      diffuse glomerulopathy, it was found that three of 31 children histologically
      diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG)
      and C3 on the glomerular capillary walls. The present study attempted to
      comparatively investigate clinical and pathological features of the diffuse group
      and the focal segmental group in 31 IMN children. Immunofluorescence study
      revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along
      glomerular capillary walls. In contrast, focal and segmental deposition of IgG
      and C3 was noted in three children with IMN. In addition, focal and segmental
      electron-dense deposits were identified in these cases. In two children of the
      focal segmental group, immunofluorescent patterns of IgG deposition were
      unchanged even at the second biopsy. The focal segmental form of IMN tended to
      occur in younger children than diffuse IMN. However, other clinical parameters
      such as the range of proteinuria, hematuria, serum albumin and prognosis did not
      show any significant differences between both groups. Electrophoretic profiles of
      urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were
      not different between both groups. It is proposed that the focal segmental form
      of IMN may have a distinctive glomerulopathy from the typical form of IMN.

PMID- 9241900
TI  - Psychosocial aspects and psychiatric disorders in children with thalassemia
      major.
AB  - beta-thalassemia major (TM), a chronic, genetically determined hematological
      disorder, has received little investigation on the psychological aspects of the
      disease and the psychosocial adjustment of patients with this anemia. In the
      present study, the aim was to assess the mental capacity, self-image,
      hopelessness and anxiety displayed by children who suffered from TM, and to
      investigate the existence of psychiatric disorders in these children. Twenty-five
      children (16 boys and 9 girls) with TM, 12.0-19.6 years old, from the Hematology
      Unit of the Department of Pediatrics at the SSK Tepecik Teaching Hospital, were
      included in the study. Fifteen healthy cases matched for age, sex and socio
      economic status were used as controls. The Wechsler Intelligence Scale for
      Children (or Wechsler Adult Intelligence Scale), Offer Self-Image Questionnaire,
      Beck Hopelessness Scale, Trait Anxiety Inventory, Symptom Check List (revised)
      and the Family Assessment Device were performed on all patients. Then, the
      patients were evaluated for a psychiatric disorder by a psychiatrist (according
      to the diagnostic criteria of the Diagnostic and Statistical Manual IV of the
      American Psychiatric Association). The results for the patients and control cases
      were compared statistically using Mann-Whitney and Kruskal-Wallis tests. Self
      image was found to be significantly lower in patients with TM than in control
      cases (P < 0.01). Hopelessness and Trait-Anxiety scores were determined to be
      significantly higher in patients with TM than in control cases (P < 0.01 and P <
      0.05, respectively). Eighty percent of the patients with TM have had at least one
      psychiatric disorder. As a result, the study showed that most of the patients
      with TM had severe psychosocial problems. Relying on these data, it was concluded
      that medical therapy of these patients should be supported with psychological aid
      and psychiatric treatment.

PMID- 9241901
TI  - Studies on the site of renal tubular defect in Bartter's syndrome.
AB  - Renal tubular function was studied in an 8-month-old male infant with Bartter's
      syndrome, which is characterized by hypokalemic metabolic alkalosis, normotensive
      hyperreninemic hyperaldosteronism, and reduced pressor response to angiotensin
      II. Chloride transport along the diluting segment (CH2O/CH2O + CCl) was impaired.
      Furthermore, furosemide did not elicit normal natriuresis, which suggested
      impaired chloride reabsorptive capacity at the furosemide-sensitive ascending
      limb of Henle's loop. Loss of antidiuretic hormone-mediated urinary concentration
      was in support of this. These findings pointed to the thick ascending limb of
      Henle's loop as the site of the primary defect in this child.

PMID- 9241902
TI  - Arthritis in a patient with homozygous familial hypercholesterolemia.
AB  - Familial hypercholesterolemia is a disorder of lipoprotein metabolism
      characterized by elevated cholesterol, low-density lipoprotein cholesterol,
      xanthomas and early onset atherosclerosis. Tendinitis and arthritis have been
      reported in patients with familial hypercholesterolemia. A report is presented of
      a 9-year-old girl with an acute arthritic attack who was diagnosed as homozygote
      familial hypercholesterolemia with hypercholesterolemic arthritis.

PMID- 9241903
TI  - Interstitial pneumonitis probably induced by cyclophosphamide in nephrosis.
AB  - A case of interstitial shadows associated with oral cyclophosphamide therapy in a
      32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to
      the Nishi-Kobe Medical Center with systemic edema, is reported. Due to the lack
      of response to prednisolone, cyclophosphamide was also administered orally at a
      dose of 3 mg/kg per day, 4 weeks after the start of steroid therapy.
      Approximately 3 weeks after the combination treatment she developed a fever, dry
      cough and cyanosis. Radiographic examination showed diffuse ground-glass shadow
      in both lungs, presumably indicating that she had interstitial pneumonitis. Her
      pulmonary signs and symptoms deteriorated despite various antimicrobial
      treatments. A discontinuation of cyclophosphamide and the administration of high
      dose methylprednisolone yielded a dramatic improvement. These findings suggest
      that the diffuse pulmonary disease in this case was induced by cyclophosphamide.
      Since interstitial pneumonitis may be fatal and irreversible, attention should be
      paid to this rare complication even in patients undergoing low-dose oral
      cyclophosphamide treatment.

PMID- 9241904
TI  - High-dose dexamethasone therapy for a 14-month-old boy with refractory idiopathic
      thrombocytopenic purpura.
AB  - A 14-month-old boy with refractory idiopathic thrombocytopenic purpura (ITP), who
      was successfully treated with pulsed high-dose oral dexamethasone therapy is
      reported. The platelet count increased after six scheduled courses of treatment
      (10 mg/day x 4 days, six courses). Twenty-four months later, the platelet count
      remained over 10.0 x 10(4)/microL. No obvious side effects were observed during
      or after the therapy. This treatment could be taken into consideration not only
      for adults but also for young children with refractory ITP. It is effective,
      safe, easy to administer, patient comfort is taken into consideration, and
      hospitalization duration and costs are minimized.

PMID- 9241905
TI  - Neonatal alloimmune thrombocytopenia associated with anti-human platelet antigen
      3a antibody.
AB  - A sister and brother with neonatal alloimmune thrombocytopenic purpura (NAITP)
      caused by maternal anti-human platelet antigen (HPA)-3a are reported. The
      children had transient severe thrombocytopenia in the newborn period, and were
      treated with intravenous gamma-globulin and platelet concentrates from random
      donors. Although the sister had intracranial hemorrhage on day 2 postnatally, the
      development of the child has been normal and no neurological sequelae have been
      observed. The brother only had bloody stool when the platelet count was low, and
      did not have severe hemorrhagic manifestations. The diagnosis of NAITP was made
      by the sera from the mother, which contained anti-HPA-3a antibody directed
      against platelets of the children. The rate of recurrence might be high in this
      family, because the father of the patients was found to be homozygous for the HPA
      3a gene.

PMID- 9241906
TI  - Prolonged isoflurane anesthesia in a case of catastrophic asthma.
AB  - A 13-year-old female patient with life-threatening asthma was treated with the
      inhalational anesthetic agent, 1% isoflurane, for 202 h (140 minimum alveolar
      concentration (MAC) hours). The patient survived and exhibited no significant
      side effects attributable to the medication. The present patient report provides
      additional clinical information supporting the utilization of long-term
      isoflurane general anesthesia in the management of refractory status asthmaticus
      that have not responded to aggressive medical management.

PMID- 9241907
TI  - Pneumoperitoneum complicating mechanical ventilation in congenital myotonic
      dystrophy.
AB  - Pneumoperitoneum is known as a disease caused by perforation of the
      gastrointestinal tract, but it has also been reported as a complication of
      mechanical ventilation. In a case of congenital myotonic dystrophy (CMyD),
      mechanical ventilation was performed to treat severe respiratory distress
      starting at birth, and then pneumomediastinum and pneumoperitoneum developed as
      complications 5 days after birth. The fact that the pneumoperitoneum improved
      when the ventilation pressure was reduced and the patient's course was observed,
      allowed us to rule out gastrointestinal perforation. It appeared that hypoplasia
      of the diaphragm may have been involved in the progression of pneumomediastinum
      to pneumoperitoneum in this patient. Mechanical ventilation is performed on many
      occasions in CMyD, and the development of pneumoperitoneum secondary to pulmonary
      air leak should always be borne in mind.

PMID- 9241908
TI  - A case of congenital Listeria septicemia associated with high levels of
      inflammatory cytokines.
AB  - A case of congenital Listeria septicemia is reported. A 2256 g male infant
      suffering from respiratory and circulatory failure with shock-like symptoms and
      high levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1
      beta, -6, and -8), was admitted to the Morioka Red Cross Hospital. Listeria
      monocytogenes was cultured from cord blood, contents from the external ear canal,
      rectum and stomach. The infant was treated with surfactant replacement as well as
      conventional therapy. The high levels of interleukin-1 beta decreased with the
      improvement of the circulatory function, which might have been the major cause of
      the poor clinical state.

PMID- 9241909
TI  - Three cases of pyogenic sacro-iliitis, and factors in the relapse of the disease.
AB  - Pyogenic sacro-iliitis (PS) is a rare disease in childhood. Three cases of PS are
      reported that were difficult to diagnose. Scintigraphy and magnetic resonance
      imaging (MRI) were useful for diagnosis. One patient suffered from an episode of
      relapse. Seventeen other cases of PS were reviewed in the literature to
      investigate the incidence of abnormal imaging findings and various factors in
      disease relapse. It was found that the incidence of abnormal findings by
      scintigraphy was significantly higher than that by computed tomography (P =
      0.0057). The duration of intravenous antibiotic administration of the relapse
      group (14.7 +/- 4.7 days) was significantly shorter than that of the non-relapse
      group (24.3 +/- 10.7 days; P = 0.0376). The statistical analysis suggested that
      intravenous antibiotic administration is necessary at least for 20 days to
      prevent a relapse of PS.

PMID- 9241910
TI  - Citrobacter koseri osteomyelitis in an infant.
AB  - A 3-week-old infant developed left shoulder swelling and was found to have septic
      arthritis and osteomyelitis of the humerus caused by Citrobacter koseri (formerly
      C. diversus). Citrobacter species are Gram-negative rods that are best known for
      their propensity to cause neonatal meningitis, ventriculitis and concomitant
      brain abscess. Non-central nervous system infections are rare. The present case
      illustrates that neonatal osteomyelitis caused by unusual organisms can present
      to pediatricians in an inner-city setting, and can respond favorably to surgical
      and medical management.

PMID- 9241911
TI  - Kabuki make-up syndrome associated with West syndrome.
AB  - A Japanese boy with Kabuki make-up syndrome associated with West syndrome is
      reported. He developed periodic tonic spasms at 6 months of age while his electro
      encephalogram also revealed hypsarrhythmia. Although only a few previously
      reported cases of Kabuki make-up syndrome have been associated with epilepsy, it
      is likely that epileptic seizures are another primary feature of Kabuki make-up
      syndrome.

PMID- 9241912
TI  - Adie's syndrome in childhood.
AB  - An 8-year-old girl with a history of mild amblyopia who had occlusion therapy,
      but her anisocoria went unnoticed, was studied. Old photographs of the patient
      were reviewed and a 0.1% pilocarpine test was performed. Review of her old
      photographs suggested that she had anisocoria at least since she was 3 years old.
      The 0.1% pilocarpine test confirmed a diagnosis of Adie's syndrome. In light of
      this case, it must be kept in mind that though rare, Adie's syndrome can be
      encountered in early childhood.

PMID- 9241913
TI  - Circulating soluble CD23 levels in Kawasaki disease with coronary artery lesions.

PMID- 9241914
TI  - Evaluating new training programs for language impairment.

PMID- 9241915
TI  - The mind-body-spirit connection.

PMID- 9241916
TI  - Tooting your own horn.

PMID- 9241917
TI  - Growing the field. Who will teach future generations?

PMID- 9241918
TI  - Do psychoacoustic skills vary in children?

PMID- 9241919
TI  - Exploring alternative medicine on the Internet.

PMID- 9241920
TI  - National treatment outcomes data for professionals and consumers.

PMID- 9241921
TI  - What if a patient refuses treatment?

PMID- 9241923
TI  - Incidence of inflammation in completely impacted lower third molars.
AB  - The influence of ageing and the contact of the adjacent tooth on purulent
      inflammation associated with the completely impacted lower third molar was
      assessed in 26 patients with clinical symptoms of infection out of 800 patients
      who had roentgenographically-confirmed completely impacted lower third molars.
      These 26 patients were 23 years of age or older. The 9 with pain alone ranged
      from 25 to 44 years of age, whereas the 17 patients with inflammation ranged from
      29 to 67 years of age, and non-contact to adjacent tooth was associated with
      purulent inflammation in older patients, indicating completely impacted lower
      third molars may cause pain only until 45 years of age; but purulent inflammation
      occurs even in the group of non-contact to adjacent tooth after 45 years of age.
      The authors recommend that a completely impacted lower third molar should be
      removed if the risk factors of advanced age and contact with the adjacent tooth
      are present.

PMID- 9241922
TI  - Inferior alveolar nerve damage following removal of mandibular third molar teeth.
      A prospective study using panoramic radiography.
AB  - Permanent alteration of sensation in the lip after the removal of mandibular
      third molar teeth is an unusual but important complication. Studies have been
      performed to assess the risk of nerve damage but most of these have been
      retrospective and poorly controlled. This prospective trial predicted the outcome
      of altered sensation prior to surgery based on assessment of a panoramic
      radiograph and correlated this with the result postoperatively in the consecutive
      removal of 479 third molar teeth. Results indicated that 5.2 per cent had
      transient alteration in sensation but only one patient (0.2 per cent) had
      prolonged anaesthesia. As 94.8 per cent of teeth extracted had no neurological
      sequelae the figures for prediction were skewed and a kappa statistical analysis
      of 0.27 illustrated a fair level of agreement between prediction and outcome.
      This study supports previously reported levels of neurological damage and
      confirms that panoramic radiography is the optimum method for radiological
      assessment for mandibular third molar teeth prior to their removal.

PMID- 9241924
TI  - Serious complications of endodontic infections: some cautionary tales.
AB  - While endodontic (dentoalveolar) abscesses can cause significant morbidity, in
      susceptible individuals they can pose life-threatening problems. This paper
      provides an overview of the more serious sequelae of endodontic abscesses, and
      provides examples of 'high risk' situations in practice in which these serious
      complications are more likely to occur.

PMID- 9241925
TI  - Supernumerary teeth: a review of the literature and four case reports.
AB  - A review of the literature relating to supernumerary teeth is presented along
      with four case reports to illustrate some possible presentations, diagnostic
      features,and treatment options.

PMID- 9241926
TI  - Safety issues related to the use of silver fluoride in paediatric dentistry.
AB  - Due to its exceedingly high fluoride content, 40% silver fluoride solution has
      the potential to cause fluorosis when used in young children. In vitro testing
      conducted in the present investigation indicates that application of 40% silver
      fluoride to deep carious lesions or its use as a 'spot' application agent could
      result in 3 to 4 mg of fluoride reaching the systemic circulation. As
      scientifically-based clinical trials on the safety of 40% silver fluoride have
      not been conducted, it would be appropriate for it to be withdrawn from further
      clinical use until proper testing and evaluation have been carried out. In view
      of the possibility that lower strength solutions of silver fluoride (1-4%) may be
      just as effective as 40% in 'arresting' deep caries, testing should focus on such
      solutions, particularly as the potential for toxicity from their fluoride content
      would be reduced by a factor of 10-40.

PMID- 9241927
TI  - Periodontal and prosthetic therapy in severely advanced periodontitis by the use
      of the crown sleeve coping telescope denture. A longitudinal case report.
AB  - The crown and sleeve-coping (CSC) telescope denture is a removable prosthesis
      that is supported by both selectively retained teeth and the residual ridge or
      mucosa. Limited information regarding longitudinal studies of the CSC telescope
      denture has been reported as to the response of the abutments and their
      surrounding periodontal tissues to this type of design. The authors have
      documented a longitudinal ten-year follow-up of a case which was considered
      'hopeless' for oral rehabilitation because of advanced periodontitis. The CSC
      telescope denture used in this case resulted in a significant improvement to the
      remaining dentition. The beneficial results of this form of treatment can be
      considered for a wide variety of clinical applications for the severely advanced
      periodontitis case.

PMID- 9241928
TI  - Familial tarda type osteogenesis imperfecta with dentinogenesis imperfecta Type
      I. Case report.
AB  - This paper presents a case of dentinogenesis imperfecta Type I occurring in a
      patient with familial tarda type osteogenesis imperfecta. The investigation and
      management of this patient is described.

PMID- 9241929
TI  - Distribution of coronal and root caries experience among persons aged 60+ in
      South Australia.
AB  - This report provides epidemiological data describing caries experience among the
      population of non-institutionalized older adults in Adelaide and Mt Gambier.
      Subjects were selected in a stratified random sample of persons aged 60+ who were
      listed on the South Australian Electoral Database. Oral examinations were
      conducted by four calibrated dentists among 853 dentate persons aged 60 years and
      over. There was an average of 14.7 missing teeth, 8.3 filled teeth and 0.3
      decayed teeth, and a further 0.2 teeth were present as retained roots. The mean
      number of missing teeth was higher (p < 0.05) in older compared with younger age
      groups, and in Mt Gambier compared with Adelaide. The mean DFS of 22.1 was
      significantly higher (p < 0.05) among younger persons, females and in Adelaide.
      Root surface caries affected an average of 3.1 surfaces, and was greater (p <
      0.05) among persons aged 70-79 years, males and Adelaide residents. However, when
      root caries was expressed as an attack rate per 100 exposed surfaces, differences
      were statistically significant only among age groups. Analysis of specific teeth
      revealed that no more than 40 per cent of molars were retained, and between 30
      and 58 per cent of retained molars had coronal fillings.

PMID- 9241930
TI  - Coronal displacement of cementum: correlation between age and coronal movement of
      cementum in impacted teeth.
AB  - This study was conducted on 48 impacted and 51 erupted maxillary permanent canine
      teeth extracted from healthy patients aged 13-73 years. Longitudinal buccolingual
      ground sections were prepared. The distance between the edges of cementum and
      enamel in each specimen was measured with an eyepiece micrometer. A correlation
      test was applied between age and the distance between enamel and cementum
      measurements. In impacted teeth, depending on age, cementum had a tendency to
      overlap the enamel; there was a linear correlation between age and coronal
      displacement of cementum (n-2 = 46, r = 0.69, distance (microgram) = 21.7* age
      (years) -440, p < 0.001). No correlation between age and coronal displacement was
      found in erupted teeth (n-2 = 49, r = -0.23, p > 0.05). Results of the study
      indicated that the cementum in impacted teeth migrated coronally during the
      ageing process. This may be related to continually erupting forces which affect
      the impacted teeth and may be a mechanism by which the teeth are protected at the
      cemento-enamel junction (CEJ). This phenomenon could be used in forensic
      dentistry to determine age. The absence of correlation in erupted teeth could be
      attributed to the masking effects of extrinsic factors.

PMID- 9241931
TI  - An improved mouthguard material.
AB  - A modified mouthguard material which reduces transmitted forces is described.
      Tests showed that the inclusion of air cells in a 4 mm thick polyvinyl-acetate
      polyethylene (EVA) copolymer reduced the effects of impacts of less than 10 kN
      when compared with a material of the same EVA composition and thickness. The EVA
      copolymer with air-inclusions is suitable for the construction of stock mouth
      formed and vacuum-formed mouthguards. The improved elastic properties of the
      modified mouthguard material reduced transmitted forces by 32 per cent when
      compared with traditional EVA mouthguard polymers of the same thickness.

PMID- 9241932
TI  - The effects of die-spacing on post-cementation crown elevation and retention.
AB  - This paper reviews the relevant dental literature concerning the effect of die
      spacing on crown elevation and pre- and post-cementation crown retention.
      Techniques of providing die-spacing and measurement of the thickness of die
      spacer are discussed. A review of the role of the provision of a cement space in
      reducing post-cementation crown elevation is presented. Factors which may affect
      crown retention prior to and following cementation are also reviewed. The
      influence of variables in techniques and experimental design on the results of
      the studies reviewed is discussed.

PMID- 9241933
TI  - Infection control and contaminated waste disposal practices in Southern Sydney
      Area Health Service Dental Clinics.
AB  - The sterilization and contaminated waste disposal practices in all 14 dental
      clinics operated by the Southern Sydney Area Health Service were surveyed. All of
      the clinics used autoclaves for sterilization. All hand instruments, handpieces
      and triplex syringes were autoclaved between patients. Chemical disinfection
      solutions were used in 12 of the 14 dental clinics, mainly for surface
      decontamination. Five dental clinics had separate storage areas for contaminated
      waste which compiled with contaminated waste separation and disposal guidelines.
      The practice of recapping needles with fingers and some inadequate washing
      facilities are areas that require particular attention.

PMID- 9241934
TI  - Trends in postgraduate education in general dentistry.
AB  - The explosion of knowledge coupled with a more diversified society have led to a
      new set of demands on dentists. For more than 20 years, dental educators and the
      profession have been concerned about the pressure on the university to ensure
      that every new graduate is fully competent to enter a dental practice
      independently and successfully. This paper reviews some of the innovations which
      are being employed to attempt to deal with these concerns. There is no one
      formula that can answer these concerns. Postgraduate training in general
      dentistry is becoming more widespread and may need further investigation. The
      main focus of this paper is on trends in formal advanced postgraduate training in
      general dentistry.

PMID- 9241935
TI  - Another dental milestone.

PMID- 9241936
TI  - Cavity classification.

PMID- 9241937
TI  - The role of anxiety sensitivity in the pathogenesis of panic: prospective
      evaluation of spontaneous panic attacks during acute stress.
AB  - Expectancy theory posits that anxiety sensitivity may serve as a premorbid risk
      factor for the development of anxiety pathology (S. Reiss, 1991). The principal
      aim of the present study was to determine whether anxiety sensitivity acts as a
      specific vulnerability factor in the pathogenesis of anxiety pathology. A large,
      nonclinical sample of young adults (N = 1,401) was prospectively followed over a
      5-week highly stressful period of time (i.e., military basic training). Anxiety
      sensitivity was found to predict the development of spontaneous panic attacks
      after controlling for a history of panic attacks and trait anxiety. Approximately
      20% of those scoring in the upper decile on the Anxiety Sensitivity Index (R. A.
      Peterson & S. Reiss, 1987) experienced a panic attack during the 5-week follow-up
      period compared with only 6% for the remainder of the sample. Anxiety sensitivity
      also predicted anxiety symptomatology, functional impairment created by anxiety,
      and disability. These data provide strong evidence for anxiety sensitivity as a
      risk factor in the development of panic attacks and other anxiety symptoms.

PMID- 9241939
TI  - Patterns of regional brain activity differentiate types of anxiety.
AB  - Previous studies have reported hemispheric asymmetries in brain activity in
      anxiety, but the direction of asymmetry has been inconsistent. A distinction
      between anxious apprehension (e.g., worry) and anxious arousal (e.g., panic), as
      types of anxiety, may account for some of the discrepancies. To test this
      proposition, the authors selected participants with self-reported anxious
      apprehension and experimentally manipulated anxious arousal. Regional brain
      activity was examined by recording electroencephalograms during rest and during
      an emotional narrative task designed to elicit anxious arousal. Overall, anxious
      participants showed a larger asymmetry in favor of the left hemisphere than did
      controls. In contrast, during the task, anxious participants showed a selective
      increase in right parietal activity. The results support the hypothesis that
      anxious apprehension and anxious arousal are associated with different patterns
      of regional brain activity.

PMID- 9241940
TI  - Shyness and low social support as interactive diatheses, with loneliness as
      mediator: testing an interpersonal-personality view of vulnerability to
      depressive symptoms.
AB  - Interpersonal approaches to depression are surveyed; it is suggested that
      interpersonal inhibition, as opposed to interpersonal excess, has been
      underemphasized as an antecedent of depression. It is proposed that shyness is a
      vulnerability factor for depressive symptoms in the absence but not in the
      presence of social support and that loneliness mediates the relation between
      shyness and depressive symptom increases. Undergraduates (N = 172) reported on
      their levels of shyness, social support, loneliness, positive and negative
      affect, and depressive symptoms, and returned 5 weeks later to complete a similar
      set of assessments. Results supported hypotheses. Participants who were shy and
      unsupported were likely to experience increases in depressive symptoms and
      decreases in positive affect, whereas other students were not. This effect was
      partially mediated by increases in loneliness and was specific to depressive
      symptoms and low positive affect; it did not apply to negative affect.

PMID- 9241938
TI  - Depression-related psychosocial variables: are they specific to depression in
      adolescents?
AB  - Although the psychosocial difficulties associated with adolescent depression are
      relatively well known, the extent to which these problems are specific to
      depression has received little attention. The authors examined the specificity to
      depression of a wide range of psychosocial variables in the following 3 groups of
      adolescents: depressed cases (n = 48), nonaffective disorder cases (n = 92), and
      never mentally ill participants (n = 1,079). The authors found 3 of the 44
      variables assessed in this study to be strongly specific to depression, and only
      the depressed participants exhibited more problematic functioning than did the
      never mentally ill controls. Three variables are as follows: self-consciousness,
      self-esteem, and a reduction in activities because of physical illness or injury.
      Eight variables were more strongly associated with depression than with
      nonaffective disorder, and 8 variables characterized both depressed and
      nonaffective disorder adolescents. Implications of these findings for
      psychosocial theories of depression are discussed.

PMID- 9241941
TI  - Comparison of cognitive models of depression: relationships between cognitive
      constructs and cognitive diathesis-stress match.
AB  - The authors examined the relationship between the cognitive components of the
      Beckian and Hopelessness models of depression by administering measures of
      dysfunctional attitudes, attributional style, and life stress to a sample of 59
      depressed adults. Confirmatory factor analyses indicated that dysfunctional
      attitudes and attributional style load on separate factors as opposed to a single
      factor. Additional analyses revealed that depressed persons conforming to
      diathesis-stress criteria according to each model were largely independent of one
      another. Results supported the conclusion that the Beckian and Hopelessness
      models of depression describe distinct cognitive constructs and refer to distinct
      subsets of depressed persons.

PMID- 9241942
TI  - Ego control, Ego resiliency, and the Five-Factor Model as predictors of
      behavioral and emotional problems in clinic-referred children and adolescents.
AB  - The relations of Ego control (EC), Ego resiliency (ER), and the Five-Factor Model
      of Personality (FFM) with behavioral and emotional problems were explored among
      116 clinic-referred children. Within the EC-ER model, Ego undercontrol was most
      important in predicting externalizing problems, and both Ego brittleness (the
      relative absence of ER) and Ego undercontrol made equal contributions to
      predicting internalizing problems. Within the FFM, Extraversion and Agreeableness
      were independent predictors of externalizing problems, whereas only Neuroticism
      predicted internalizing problems. When the EC-ER model was tested against the
      FFM, the latter model appeared to outperform the former in predicting
      externalizing but not internalizing problems; when clinical syndrome groups were
      examined, dimensions from both personality models were differentially salient for
      children with primary internalizing, externalizing, or comorbid problems.

PMID- 9241943
TI  - Social phobia and positive social events: the price of success.
AB  - Patients with generalized social phobia (N = 32; 16 men, 16 women) and
      nonclinical control participants (N = 32; 16 men, 16 women) took part in a social
      interaction that was manipulated to be successful or unsuccessful. Participants
      rated their ability, perceptions of others' standards, social goals, and
      emotional responses before and after the interactions. As predicted, the
      successful social interaction produced a somewhat negative response in patients
      with social phobia. Social success led to self-protective social goals, negative
      emotional states and perceptions that others would expect more in future
      interactions. These results indicate that positive social events may not be
      processed in a way that leads to a revision of negative self- and social
      judgments in patients with social phobia.

PMID- 9241944
TI  - Pursuing the psychopath: capturing the fledgling psychopath in a nomological net.
AB  - The present article reports on an attempt to import the concept of psychopathy at
      the childhood level. Childhood psychopathy was assessed in 430 boys ages 12 and
      13 years by using caretaker reports on a translation of an adult psychopathy
      assessment instrument. A systematic construct validation approach revealed that
      childhood psychopathy fits into the nomological network surrounding adult
      psychopathy. Children with psychopathic personalities, like their adult
      counterparts, were serious and stable offenders, impulsive, and more prone to
      externalizing than internalizing disorders. Childhood psychopathy also provided
      incremental validity in predicting serious stable antisocial behavior in
      adolescence over and above other known predictors and one other classification
      approach. These results suggest that psychopathy has a childhood manifestation
      that can be measured reliably. Implications and future directions are outlined.

PMID- 9241945
TI  - Genetic and environmental contributions to depression symptomatology: evidence
      from Danish twins 75 years of age and older.
AB  - The heritability symptoms of depression were investigated in a sample of 406 same
      sex Danish twin pairs 75 years of age and older. Twins completed an interview
      assessment that included symptoms of depression, which were scored on the
      following 3 scales: Somatic, Affect, and Total. Heritability estimates (h2) for
      the Total (h2 = .34), Somatic (h2 = .31), and Affect (h2 = .27) scales were all
      moderate and statistically significant. For not one of the scales did h2 vary
      significantly over the age range sampled, and although the observed twin
      correlations were substantially smaller among men as compared with women, none of
      the sex differences in heritability were statistically significant. Multivariate
      analyses indicated that all of the heritable effects on the Affect and Somatic
      subscales could be attributed to a single genetic factor. Depression symptoms in
      older adults may thus be more heritable than indicated in previous studies,
      although nonshared environmental factors clearly account for a majority of the
      variance. The implications of these findings for understanding the nature of late
      life depression symptomatology are discussed.

PMID- 9241946
TI  - Negative life events and time to recovery from episodes of bipolar disorder.
AB  - The authors of the current study examined the impact of severe negative life
      events on time to recovery from episodes of bipolar disorder. Although negative
      life events have been shown to influence relapse in bipolar disorder, research
      has not focused on life events and recovery in bipolar disorder. The authors
      recruited 67 individuals with bipolar disorder during hospitalization and
      conducted monthly assessments for at least 1 year. Individuals with severe
      negative life events took more than 3 times as long to achieve recovery as those
      without severe life events, and the impact of life events was not mediated by
      medication compliance. These results reveal that the psychosocial environment may
      play a much larger role in the course of bipolar disorder than previous
      biological models have suggested.

PMID- 9241947
TI  - Pupillary responses index overload of working memory resources in schizophrenia.
AB  - The authors examined the hypothesis that schizophrenia patients have reduced
      availability of working memory resources by using pupillary responses as an index
      of resource overload. Pupillary responses were recorded during a verbal working
      memory task (digit recall) in 24 schizophrenia patients and 32 normal controls.
      Pupil size increased with increased processing load (digit-span length) but
      changed little or declined when processing demands exceeded available resources
      (overload). The schizophrenia patients showed impaired digit recall and
      abnormally small pupillary responses during digit presentation only in the higher
      processing load conditions, but they showed abnormally small pupillary responses
      during digit retrieval in all processing load conditions. The results suggest
      reduced availability of slave store and central executive working memory
      resources in schizophrenia. This study serves as an example of how pupillography
      methods can be used to test current hypotheses regarding overload of cognitive
      capacities in schizophrenia patients.

PMID- 9241948
TI  - Antisaccade performance in patients with schizophrenia and affective disorder.
AB  - The authors examined psychotic patients with schizophrenia, major depression, and
      bipolar disorder; "normal" participants; and 1st-degree relatives of patients
      with schizophrenia on an antisaccade task in which participants were instructed
      to move their eyes in the opposite direction of a target that moved unpredictably
      and abruptly either to the left or right of central fixation. Patients with
      schizophrenia were found to make significantly more errors than their relatives,
      and the latter made more errors than the controls. The poor performance of the
      relatives could not be attributed to their having a psychiatric disorder.
      Comparison of the 3 patient groups indicated that antisaccade deficits were more
      pronounced in schizophrenia and bipolar disorder.

PMID- 9241949
TI  - Antisocial personality disorder, conduct disorder, and substance abuse in
      schizophrenia.
AB  - The validity of subtypes based on antisocial personality disorder (APD) or
      childhood conduct disorder without adult APD (CD only) in patients with
      schizophrenia (or schizoaffective disorder) and a substance use disorder (abuse
      or dependence) was examined. APD patients scored lower on personality measures
      related to socialization and higher on antisocial behavior, psychopathy, and
      aggression. APD patients also reported higher rates of aggression and legal
      problems. APD, and to a lesser extent CD only, was associated with more severe
      psychiatric symptoms, an earlier age of onset of substance abuse, more severe
      symptoms of substance abuse, and a stronger family history of substance abuse and
      psychiatric hospitalization. The findings suggest that schizophrenia patients
      with APD represent a high-risk subgroup vulnerable to more severe substance
      abuse, psychiatric impairment, aggression, and legal problems.

PMID- 9241950
TI  - The association between social support and course of depression: is it confounded
      with personality?
AB  - A number of studies have indicated that social support is associated with the
      course of depression. However, none of these studies have ruled out the
      potentially confounding effects of personality factors, such as neuroticism. The
      authors examined whether social support was related to the course of depression
      after controlling for neuroticism and several possible confounding clinical
      variables. Participants were 59 patients meeting Diagnostic and Statistical
      Manual of Mental Disorders (American Psychiatric Association, 1987) criteria for
      major depression. All participants received structured diagnostic interviews and
      completed self-report measures of social support and neuroticism. Follow-up
      assessments at 6 months included the Longitudinal Interval Follow-Up Evaluation
      (M. B. Keller et al., 1987) and the Beck Depression Inventory (A. T. Beck, A. J.
      Rush, B. F. Shaw, & G. Emery, 1979). Results indicated that social support
      significantly predicted both severity of depression and recovery from depression
      at follow-up over and above the effects of initial depression severity,
      dysthymia, and neuroticism.

PMID- 9241951
TI  - Behavioral analysis of drinking behaviors in polydipsic patients with chronic
      schizophrenia.
AB  - The authors describe drinking and voiding behaviors that differentiate between
      psychiatric patients with polydipsia and patient controls. Observations of 9
      polydipsic patients and 6 controls were conducted for 153 hr and had high
      interrater reliability. Polydipsic patients drank 3 times as frequently,
      ingesting 5 times as much fluid as the controls. They voided 4 times as often,
      eliminated 5 times as much urine, and evidenced greater diurnal weight shifts. A
      higher bout frequency and a shorter time interval between drinks differentiated
      polydipsic patients from controls, whereas amount drunk per bout and rate of
      drinking were similar across groups. The authors' findings have implications for
      improving detection of polydipsia, understanding its neurobiology, and developing
      more efficacious behavioral interventions.

PMID- 9241952
TI  - Cognitive processing and trait anxiety in typically developing children: evidence
      for an interpretation bias.
AB  - In this study the authors examined whether increases in children's levels of self
      reported trait anxiety would be related to their interpretation of ambiguous
      stimuli. By using the Revised Children's Manifest Anxiety Scale (C. R. Reynolds &
      B. O. Richmond, 1985), the authors obtained measurements of anxiety for 40
      children ages 7 and 9 years. Interpretation of ambiguous stimuli was measured by
      using a pictorial homophone task, where homophones could be interpreted as either
      threatening or neutral. Results showed that children's interpretations of
      homophones was significantly predicted by level of anxiety. Increases in levels
      of trait anxiety were positively associated with threatening interpretations of
      homophones.

PMID- 9241953
TI  - Magical ideation and social anhedonia as predictors of psychosis proneness: a
      partial replication.
AB  - The authors compared college students identified by high scores on the Magical
      Ideation Scale (M. Eckblad & L. J. Chapman, 1983) and the Revised Social
      Anhedonia Scale (MagSoc; n = 28; M. Eckblad, L. J. Chapman, J. P. Chapman, & M.
      Mishlove, 1982) with control participants (n = 20) at a 10-year follow-up
      assessment in an attempt to replicate L. J. Chapman, J. P. Chapman, T. R. Kwapil,
      M. Eckblad, and M. C. Zinser's (1994) report of heightened psychosis proneness in
      MagSoc individuals. The MagSoc group exceeded the control group on severity of
      psychotic-like experiences; ratings of schizotypal, paranoid, and borderline
      personality disorder symptoms; and rates of mood and substance use disorders. Two
      of the MagSoc participants but none of the control participants developed
      psychosis during the follow-up period (a nonsignificant difference). Consistent
      with L. J. Chapman et al.'s findings, the groups did not differ on rates of
      personality disorders or relatives with psychosis.

PMID- 9241954
TI  - Dentine permeability and dentine adhesion.
AB  - OBJECTIVES: The objectives of this paper are to review the structure of dentine
      as it pertains to adhesive bonding and to describe the importance of resin
      permeation into dentinal tubules and into spaces created between collagen fibrils
      by acid-etching during resin bonding. The advantages and disadvantages of
      separate acid-etching, priming and adhesive applications are discussed. DATA
      SOURCES: Although not an exhaustive review, the concepts included in the review
      were obtained from the dentine bonding literature. STUDY SELECTION: Attempts were
      made to critically evaluate what is known about dentine permeability and adhesion
      and what remains to be discovered. Speculations were made on a number of
      controversial issues that are not yet resolved. CONCLUSIONS: Acid-etching of
      dentine produces profound changes in the chemical composition and physical
      properties of the matrix which can influence the quality of resin-dentine bonds,
      their strength and perhaps their durability.

PMID- 9241955
TI  - Prolonged antimicrobial effect of tissue conditioners containing silver-zeolite.
AB  - OBJECTIVES: The purpose of this study was to elucidate the in vitro antimicrobial
      effect of tissue conditioners containing silver-zeolite on Candida albicans and
      nosocomial respiratory infection-causing bacteria, Staphylococcus aureus and
      Pseudomonas aeruginosa. METHODS: Five commercially available tissue conditioners
      were selected: Visco-gel (VG), GC Soft-Liner (SL), Fitt (FT), SR-Ivoseal (IV) and
      Shofu Tissue Conditioner (TC). Samples, 10 x 10 x 2.5 mm in size, contained
      silver-zeolite (SZ sample) and no SZ (N sample). The antimicrobial effects of
      these two samples were evaluated as a percentage of viable cells (CFU) in a
      microbial suspension (100 microliter) in phosphate-buffered saline with or
      without immersion in artificial saliva for four weeks. The borderline of the
      antimicrobial effect was determined at 0.1% viable cells. RESULTS: With the SZ
      samples, all tested microbes were killed under both conditions of no immersion
      and immersion in saliva. In non-immersed N samples, however, no cells of C.
      albicans (except with VG) and S. aureus survived, whereas the percentage of
      viable cells of P. aeruginosa was similar to that found in the control. However,
      with immersion in saliva, viable cells of C. albicans in some N samples (VG, SL
      and TC) increased compared with non-immersion samples by more than 0.1%.
      CONCLUSION: Tissue conditioners containing SZ have been shown to have
      antimicrobial effects for four weeks on C. albicans and nosocomial respiratory
      infection-causing bacteria in saliva in vitro.

PMID- 9241956
TI  - Mapping of tubule and intertubule surface areas available for bonding in Class V
      and Class II preparations.
AB  - OBJECTIVES AND METHODS: The aim of this in vitro study was to evaluate the
      morphology of dentine in Class V and the Class II preparation walls in terms of
      tubule orientation, density and increase in surface area after conditioning. Six
      circular V-shaped preparations were cut at the cementum-enamel junction (CEJ) of
      anterior teeth and six Class II cavities with the cervical margin 1 mm below the
      CEJ were prepared in posterior teeth. The preparations were conditioned with 10%
      maleic acid. The samples were directly studied by SEM. The observations were
      organized according to location in the preparation, tubule density was counted
      and the increase in area available for bonding after acid etching was calculated.
      RESULTS: Dentine morphology of Class V and Class II preparation walls was mostly
      regular according to predictable patterns. Between the tubules, along the walls
      of the cavity, the etched dentine surface exhibited a porous network of collagen
      fibers. More than 50% of Class V and Class II cavity surface presented oblique or
      parallel tubule orientation with respect to the cut surface. Because of the
      presence of a structureless cementum layer. the morphology of the cervical area
      turned out to be less predictable. The tubule density varied considerably in
      different regions of the preparations. The intertubular dentine surface area
      increased after conditioning in Class V preparations from 20.9% to 50.3% on the
      walls where tubules were cut parallel to their long axis, and from 5.8% to 47.8%
      where tubules were cut perpendicularly. These same values for Class II
      preparations ranged from 0.6% to 46.4% on the walls where tubules were cut
      parallel to their long axis, and 29.8% of the tubules were cut perpendicularly.
      CONCLUSIONS: Based on this morphological investigation, the increase in
      intertubular dentine surface area might very well be responsible for the enhanced
      bond strength after acid etching of dentine, but not all areas exhibited equal
      responses to etching. In particular, the bonding substrate at the gingival
      margins may contribute little in terms of micromechanical retention.

PMID- 9241957
TI  - Adaptation and radiographic evaluation of four adhesive systems.
AB  - OBJECTIVES: The purpose of this study was to compare microleakage, gap formation,
      thickness of the adhesive layer and its radiographic appearance associated with
      four adhesive restorative procedures for class I cavities. METHODS: Adhesive
      systems with easy handling characteristics were selected for the restoration of
      class I cavities in extracted third molars. Bitewing radiographs were taken of
      each tooth and four observers were asked to assess the presence of the adhesive
      layer. Microleakage, gap width and the thickness of the adhesive layer of each
      restoration were measured upon sectioning of the teeth. RESULTS: Microleakage in
      the experimental restorations was minimal. The thickness of the adhesive layers
      and gap formation varied among different adhesive systems. The adhesive system
      with self-etching primer produced the highest percentage gap-free restorations.
      Thick adhesive layers could be detected on the radiograph. ROC analysis of the
      results validates the diagnosis from the radiograph. CONCLUSIONS: The four
      restorative systems performed well in the prevention of microleakage. The use of
      a resin modified glass-ionomer cement base did not prevent gap formation compared
      with the all-etch bonding systems used in this study. The presence of an adhesive
      layer contributed to the prevention of gap formation, independently of the
      bonding system used. Thick adhesive layers could be detected on the radiograph.

PMID- 9241958
TI  - The transverse strength, reliability and microstructural features of four dental
      ceramics--Part I.
AB  - OBJECTIVES: The flexural strength, reliability and microstructure of a heat
      pressed ceramic system (Empress) was evaluated in comparison with three current
      frit materials used in ceramic crown and inlay construction. METHODS: Twenty bar
      specimens per material were constructed, overglazed and transverse tested at a
      crosshead speed of 0.5 mm/min. Etched and fractured bar specimens were viewed
      under a scanning electron microscope using secondary electron imaging. RESULTS:
      Mean strengths (MPa +/- SD) were: Empress, 117.3 +/- 31.7; Cerinate porcelain,
      118.2 +/- 8.7; Corum porcetain, 92.9 +/- 13.3; and Alpha porcelain, 60.9 +/-
      10.1. Results were highly significant (P < 0.001) with differences between all
      groups (P < 0.05) except Cerinate porcelain and Empress (P > 0.05). Weibull
      analysis of the results provided m-values and the predicted strength at the 1 and
      5% probabilities of failure. Microstructural examination using secondary electron
      imaging showed leucite crystals 1.6-3.5 microns and associated microcracking in
      Corum porcelain and leucite crystal clusters (1.5 microns) in Empress. Cerinate
      porcelain exhibited a uniform distribution of fine leucite crystals (1 micron).
      Spherical porosity combined with crack pore combinations were noted in Vita Alpha
      porcelain. CONCLUSIONS: Empress glass ceramic was not stronger than Cerinate or
      more reliable than many of the frit materials. Uniform leucite distribution and
      fine crystal size may be associated with improved strength and reliability.

PMID- 9241959
TI  - The biaxial flexural strength and reliability of four dental ceramics--Part II.
AB  - OBJECTIVES: The biaxial flexural strength and reliability of four dental ceramics
      including: Empress glass ceramic (EM), Cerinate porcelain (CE), Corum porcelain
      (CO) and Alpha porcelain (AL) were compared. METHODS: Twenty disc specimens per
      material were prepared overglazed and tested. The piston on three ball test was
      used to test the specimens in a universal testing machine at a crosshead speed of
      0.15 mm/min. Weibull analysis provided m-values and the 1 and 5% probabilities of
      failure. RESULTS: Mean strengths (MPa +/- SD) were: EM, 133.5 +/- 21.5; CE, 109.1
      +/- 11.3; CO, 119.8 +/- 19.2; and AL, 68.2 +/- 9.9. There was no statistical
      difference between EM or CO and CO and CE strengths (P > 0.05). Weibull m-values
      included: EM, 6.60; CE, 10.20; CO, 5.27; and AL, 6.93. Cerinate had the highest m
      value (P < 0.01) and good dependability. CONCLUSION: Empress was not stronger or
      more reliable than many of the frit materials.

PMID- 9241960
TI  - An investigation of debonding between heat-cured PMMA and titanium alloy (Ti-6A1
      4V).
AB  - OBJECTIVES: The bonding of acrylic resin to dental prostheses constructed from
      metal has been the subject of extensive research in recent years, much of it
      between base-metal alloys such as Ni-Cr alloys and dental composite. The
      development of techniques for the manufacture of dental appliances from titanium
      and titanium alloys has opened new avenues for investigation of the metal/acrylic
      resin bond. METHODS: In this study, a bond strength comparison between two PMMA
      products, Trevalon and Metadent, and discs of titanium alloy, Ti-6A1-4V, was
      investigated using a four-point bend test configuration. Trevalon is a standard,
      commercially available, heat-cured acrylic resin, while Metadent is an acrylic
      resin incorporating a chemical bonding agent, 4-META. A comparison was made
      between two processes that are routinely used to enhance the bond between metal
      and acrylic, namely sandblasting of the metal surface and using the Silicoater
      system following sandblasting. Each of the samples was paired, thus allowing a
      further comparison to be made between samples that had undergone thermocycling in
      a water bath, with those that had been held at a constant temperature. RESULTS:
      The study revealed that a superior metal/acrylic bond was achieved by the use of
      the silicoating system when either Trevalon or Metadent was used both before and
      after thermocycling. Reduced debonding loads were recorded for all samples that
      had undergone thermocycling. CONCLUSIONS: Highest bond strengths were recorded
      for Trevalon or Metadent processed against a silicoated Ti-alloy surface.

PMID- 9241961
TI  - Effect of burnout temperatures on strength of phosphate-bonded investments--Part
      II: Effect of metal temperature.
AB  - OBJECTIVES: It had previously been found that the strength of phosphate-bonded
      investments is temperature sensitive. However, while the effect of heat from the
      cast metal is expected to have some effect on continued reactions and melting,
      there is no published report dealing with this. It was the purpose of this study
      to consider further the effects of burnout temperature on strength and the
      contribution of metal casting temperature and investment composition. METHODS:
      The disc-rupture test (Luk, H. W.-K. and Darvell, B. W., Strength of phosphate
      bonded investments at high temperature. Dental Materials 1991, 7, 99-102) was
      employed to determine the effect of burnout temperature (ranging from 400 to 1000
      degrees C) on the 'actual' strength of six phosphate-bonded investments; the cast
      metal temperature was controlled to be the same as that of the mould. Atomic
      absorption was employed to investigate aspects of the composition of the
      investments. RESULTS: The 'actual' strength obtained in this test was always
      higher than the 'service' strength observed in similar testing with the metal at
      a fixed temperature (1460 degrees C). The 'actual' strength was also temperature
      sensitive, but with a different pattern of variation compared with the 'service'
      values. All investments tested were found to behave plastically at high
      temperatures. Calcium, sodium, zinc and iron were found in appreciable quantities
      in the investments. CONCLUSION: Heat from the high-temperature casting metal has
      a material effect in decreasing the strength of phosphate-bonded investments.
      Such heating increases the plastic behaviour of the investment and this, together
      with the casting pressure, may result in a distorted mould and thus inaccurate
      castings, a hitherto unrecognized source of error. 'Actual' strength gives no
      guide to the 'service' strength, emphasizing the need for tests under service
      conditions. Composition affects investment high-temperature strength
      substantially.

PMID- 9241962
TI  - The use of lignocaine in dental practice: results of a survey of a group of
      general and hospital dental practitioners.
AB  - OBJECTIVES: This survey investigated whether dentists using lignocaine with
      adrenaline used aspiration syringes or warming and assessed their knowledge of
      appropriate doses of these drugs. METHODS: Sixty-two general dental practitioners
      (GDPs) and 26 hospital dental practitioners (HDPs) responded to a series of
      questions asked via telephone or direct interview. RESULTS: Only 3% of dentists
      interviewed correctly calculated the amount of lignocaine (mg) in 2 ml of 2%
      lignocaine solution and none knew the safe dose expressed as mg/kg body wt. All
      dentists were using a cartridge system and had an easily remembered maximum
      number of cartridges that they would administer. This number varied, but in all
      cases was within the safe maximum dose recommended by the British National
      Formulary. The survey also showed that 63% of the GDPs were using self aspirating
      syringe systems and approximately 50% considered warming the anaesthetic solution
      prior to injection to be beneficial. CONCLUSION: The results indicate that
      dentists may be found to be poor at calculating doses but are nevertheless
      unlikely to give inappropriate amounts of lignocaine to healthy adults. This
      indicates the relative safety of the cartridge system. The use of the self
      aspirating syringe is not universal in spite of recommendations for its use.
      Warming of the anaesthetic solution is popular.

PMID- 9241963
TI  - In vitro comparison between mouse B16 and human melanoma cell lines of the
      expression of ICAM-1 induced by cytokines and/or hyperthermia.
AB  - The expression of intercellular adhesion molecule-1 (ICAM-1) in mouse B16 and
      human melanoma cell lines was investigated by indirect immunofluorescence using a
      FACScan analyzer. Mouse B16 melanoma cell lines (B16-F1 and F10) did not express
      ICAM-1 under ordinary culture conditions. Neither in vitro hyperthermia at 41
      degrees C for 3 or 6 hr nor cytokines such as gamma interferon (IFN-gamma) or
      tumor necrosis factor alpha (TNF-alpha) induced ICAM-1 expression in B16 melanoma
      cell lines. A combination of IFN-gamma with TNF-alpha caused slight induction of
      ICAM-1 expression in the B16-F10 melanoma cell line. Hyperthermia at 41 degrees C
      for 3 hr in combination with the cytokines induced a slight expression of ICAM-1
      in the B16-F1 melanoma cell line. Hyperthermia at 41 degrees C for 3 hr or 6 hr
      did not induce de novo ICAM-1 expression but hyperthermia at 43 degrees C for 6
      hr caused rather suppression of the expression of ICAM-1 in the three human
      melanoma cell lines tested. In contrast, they showed a clear increase in the
      expression of ICAM-1 after treatment with either with IFN-gamma or TNF-alpha, and
      the expression was further augmented by a combination of the two cytokines.
      Treatment with cytokines in combination with hyperthermia at 41 degrees C or 43
      degrees C for 3 hr did not augment the expression of ICAM-1 over that in cytokine
      treated human melanoma cell lines, at normal temperatures. Thus, it is concluded
      that mouse B16-F1 and F10 melanoma cell lines are different from human melanoma
      cell lines in terms of induction of ICAM-1 expression by cytokines and/or
      hyperthermia.

PMID- 9241964
TI  - Disaggregation of corneocytes from surfactant-treated sheets of stratum corneum
      in hyperkeratosis on psoriasis, ichthyosis vulgaris and atopic dermatitis.
AB  - To elucidate the pathogenesis of impaired barrier function and the influence of
      surfactant on the stratum corneum in hyperkeratosis, we investigated
      morphological alterations of the corneocytes with soap solution. Groups of five
      patients each with psoriasis vulgaris (PV), ichthyosis vulgaris (IV), atopic
      dermatitis (AD), and normal controls were examined. Four samples of the horny
      layer were obtained from the same site by cyanoacrylate adhesive biopsy. The
      first sample was used for the superficial layer, and the fourth, for the basal
      horny layers. Each sample was agitated in 1% stirred soap solution at 60 degrees
      C. The number and size of isolated corneocytes and the morphologic changes were
      investigated. The release of corneocytes was greater and the swelling and
      morphological changes of corneocytes exposed to soap solutions were less in PV
      and AD than in IV or in healthy subjects. In IV, the release was markedly less
      than in controls. The release and swelling were greater in the superficial than
      in the basal horny layers. It was concluded that the cohesiveness of corneocytes
      was probably less in PV and AD and greater in IV than in normals. It was also
      suggested that the cohesion of corneocytes from the superficial horny layer was
      less than that from the deep layer. The permeability of the cornified envelope in
      PV and AD patients was less than in IV or healthy subjects. It was confirmed that
      highly potent soaps induce loss of many corneocytes and reduce the barrier
      function of the stratum corneum.

PMID- 9241965
TI  - Phenotypic differences between human blood monocyte subpopulations in psoriasis
      and atopic dermatitis.
AB  - Peripheral blood monocytes seem to be of importance in the initiation and
      maintenance of cutaneous inflammatory disorders such as psoriasis and atopic
      dermatitis. Functional abnormalities of monocytes have been observed in both
      diseases. We sought to determine whether these abnormalities are reflected by an
      altered phenotypic expression of functionally active surface molecules.
      Peripheral blood monocyte subsets varying in cellular density and cell size from
      patients with psoriasis and atopic dermatitis were investigated using FACS
      analysis employing a panel of monoclonal antibodies (CD14, CD16, HLA-DR, HLA-DO,
      Fc epsilon RII, IL-2R, ICAM-1, CR3). Furthermore, the modulation of expression by
      interferon-gamma in monocyte subsets from patients was compared to normal
      controls. The results show that HLA-DR and -DQ expression on monocyte subsets in
      psoriatic patients was significantly decreased; "large" monocytes expressed
      significantly less HLA-DR than "small" monocyte subpopulations. Decreased HLA-DR
      and -DQ expression could be upregulated by incubation of psoriatic monocytes with
      IFN gamma. In atopic dermatitis, a different phenotype pattern of monocyte
      subsets was demonstrated: HLA-DR expression and HLA-DQ expression were both
      decreased in both "large" and "small" monocytes as compared to normal controls.
      However, there were no significant differences in HLA-DR and HLA-DQ expression
      between "large" and "small" monocyte subpopulations in atopic dermatitis.
      Moreover, the ICAM-1 and IL-2R expression of "large" and "small" monocyte
      subpopulations was significantly decreased in atopic patients from levels in
      normal controls and psoriatic patients. The altered expression of HLA-DR, -DQ
      ICAM-1 and IL-2R could be upregulated by incubation of atopic monocytes with IFN
      gamma. In addition, there was a significant increase in the percentage of
      monocytes in the differential count of patients with psoriasis or atopic
      dermatitis. We conclude that the differential phenotype pattern of surface
      molecules on monocytes in psoriasis and atopic dermatitis may reflect an abnormal
      monocyte maturation/differentiation state. This may explain the functional
      abnormalities of monocytes observed in patients with psoriasis and atopic
      dermatitis.

PMID- 9241966
TI  - Langerhans cell histiocytosis (histiocytosis X) with morphologic expression of
      desmosomes and microvillous structures.
AB  - An unusual case of Langerhans cell histiocytosis in a 7-year-old female is
      presented. She had ultrastructural evidence of desmosomal biogenesis and
      formation of gland-like structures by lesional cells; their apical plasma
      membranes were folded into large numbers of microvilli. Despite the presence of
      these structures characteristic of epithelial cells, an infiltrated plaque on the
      abdominal skin of this patient was interpreted as cutaneous involvement of
      multiple system Langerhans cell histiocytosis because the immunohistochemical
      staining of the lesional cells for CD1a, S100, PNA, CD4, EN-4, and HLA-DR was
      positive, and numerous Birbeck granules were ultrastructurally identified in some
      lesional cells. Other clinical data included the presence of scaly erythematous
      skin lesions on the forehead and lytic osseous lesions in the maxilla, which were
      also histologically diagnosed as Langerhans cell histiocytosis. The absence of
      any internal malignancy in this patient readily ruled out the other diagnostic
      possibility of a metastatic adenocarcinoma showing glandular differentiation with
      brush border morphogenesis. The possibility that the desmosome-linked lesional
      epithelioid cells were actually cells of sweat glands entrapped in the
      histiocytic proliferation was also ruled out. The functional significance of the
      desmosomes and microvillous structures in the present case of Langerhans cell
      histiocytosis remains to be clarified. Awareness of this variant of Langerhans
      cell histiocytosis will be important for averting potential misdiagnosis in favor
      of epithelial tumors, especially metastatic adenocarcinomas.

PMID- 9241967
TI  - A case of pigmented dermatofibrosarcoma protuberans (Bednar tumor).
AB  - The present paper reports a 67-year-old male with pigmented dermatofibrosarcoma
      protuberans (Bednar tumor) on his right shoulder. The lesion had recurred twice.
      Clinically, the lesion was a reddish-brown, exophytic, multilobular, firm nodule
      with an irregular surface, which measured 6.4 x 4.2 cm. Histologically, the
      proliferated fibroblasts showed a cartwheel pattern and stained positively with
      CD34, similar to those of a common dermatofibrosarcoma protuberance. However,
      many melanin-bearing cells that were positive for the S-100 protein were found
      intermingled among the tumor cells. Based on these findings, we concluded that
      the clinical manifestations, level of malignancy, and cytological features, as
      well as the exception of melanin-bearing dendritic cells associated with
      pigmented dermatofibrosarcoma protuberans, suggest a common dermatofibrosarcoma
      protuberans. This supports the hypothesis that pigmented dermatofibrosarcoma
      protuberans is a pigmented variant of dermatofibrosarcoma protuberans. Thus, this
      type of tumor is not benign, but is an intermediate malignant tumor.

PMID- 9241968
TI  - Acanthosis nigricans associated with hepatolenticular degeneration.
AB  - Acanthosis nigricans and hepatolenticular degeneration (Wilson's disease)
      developed simultaneously in a 16-year-old boy. The diagnosis of Wilson's disease
      was based on the clinical presentation, including Kayser-Fleischer ring,
      hypoceruloplasminemia, hypocupremia, and hypercupriuria. His skin lesions were
      characterized by thick, dark brown, verrucous plaques on the dorsa of both feet,
      the neck, axillae, and groin. The histological findings were compatible with
      acanthosis nigricans. Six months after treatment with D-penicillamine, two grams
      per day, his skin lesions and neurological symptoms were much improved and no
      complications were observed.

PMID- 9241969
TI  - Concurrent cytomegalovirus, M. tuberculosis and M. avium-intracellulare cutaneous
      infection in an HIV patient.
AB  - We report a 25-year-old HIV-positive man with a past medical history of
      disseminated cytomegalovirus (CMV) infection, who developed cutaneous lesions
      during a disseminated mycobacterium infection. The histological changes of CMV
      and acid-fast bacilli were seen on histopathology of the lesions. Cultures were
      positive for M. tuberculosis and M. avium-intracellulare (MAI). CMV is frequently
      isolated from HIV patients, but skin involvement is rare. The association of CMV
      and mycobacteria can occur in cutaneous lesions of AIDS patients, but concurrent
      cutaneous involvement of CMV, M. tuberculosis, and MAI is unusual. These findings
      emphasize the polymorphous presentation of infectious disorders in AIDS patients
      and the need for multiple biopsies and for special stains in such patients.

PMID- 9241970
TI  - Plantar thrombotic nodules with marked neovascularization in diabetes: a symptom
      which has been overlooked?
AB  - A 69-year-old woman with diabetes has had multiple subcutaneous nodules on the
      soles for 11 months. She suffered from uncontrolled diabetes mellitus,
      hypercholesteremia, and cardiovascular thrombosis and had a past history of
      photocoagulation therapy for proliferative diabetic retinopathy. Histological
      examination revealed vascular thrombosis surrounded by neovascularization in the
      subcutaneous tissue. The basement membranes of vessels were thickened and
      strongly stained with periodic acid-Schiff. An increased serum concentration of
      von Willebrand factor antigen was observed. With control of her diabetes, the
      nodules almost disappeared. Her curious skin manifestation is speculated to be a
      diabetes-mellitus-related change in which endothelial injury and the subsequent
      induction of angiogenetic factors may play important roles. It is possible that
      this kind of skin manifestation has been overlooked or not examined
      histopathologically.

PMID- 9241971
TI  - Multiple fixed drug eruptions (MFDE) following continuous cotrimoxazole (TMP +
      SMZ) therapy.

PMID- 9241972
TI  - Team approach toward lower extremity amputation prevention in diabetes.
AB  - Through a discussion of the etiology and pathology of diabetic foot lesions with
      particular emphasis on ulceration and osteoarthropathy, the author will develop a
      plan for treatment and prevention using a multidisciplinary approach to such
      problems. Underlying risk factors including neuropathy, ischemia, infection, and,
      especially high pressures must be evaluated and appropriately ameliorated in
      order to promote resolution and avoidance of recidivism. Accordingly,
      conservative management with pressure-relieving devices, topical therapies, and
      prophylactic surgery on structural deformities plays an integral part in the
      overall podiatric management of the high-risk foot in diabetes mellitus.

PMID- 9241973
TI  - Screening techniques to identify the diabetic patient at risk of ulceration.
AB  - Foot problems are common in diabetic patients, with neuropathy and peripheral
      vascular disease being the main causative factors. Identification of high-risk
      feet can be accomplished by using basic clinical skills and simple equipment.
      Limb amputation is the most preventable of the long-term diabetes complications
      and a multidisciplinary approach can achieve a dramatic reduction of major limb
      amputations.

PMID- 9241974
TI  - Teaching diabetic foot care effectively.
AB  - Patient education is a fundamental aspect of the management of foot ulcers in the
      patient with diabetes mellitus. Preventive measures have to be focused on the
      individual risk profile of the patient and on the chronology of appearance of
      symptoms. Teaching issues need to be adapted into the following three stages: A)
      before: prevention of foot ulceration in the at-risk patient; B) acute:
      prevention of extension of an existing ulcer; and C) after: prevention of
      recurrence.

PMID- 9241975
TI  - Surgical morbidity and the risk of amputation due to infected puncture wounds in
      diabetic versus nondiabetic adults.
AB  - We reviewed the hospital course of 77 diabetic and 69 nondiabetic subjects who
      had incision, drainage, and exploration of infected puncture wounds of the foot.
      Diabetics were 5 times more likely to have multiple operations and 46 times more
      likely to have a lower extremity amputation than nondiabetics. The interval from
      injury to surgery was significantly longer in diabetics than nondiabetics. Total
      lymphocyte count and hemoglobin, hematocrit, and albumin values were
      significantly lower in diabetics than in nondiabetics. Diabetic amputees had
      higher prevalences of nonpalpable pulses, nephropathy, neuropathy, and
      osteomyelitia as compared with diabetic nonamputees. The neuropathic diabetic
      foot is not protected by pain. When combined with other comorbid factors, this
      may increase morbidity associated with puncture wounds of the foot.

PMID- 9241976
TI  - Lower extremity macrovascular disease in diabetes.
AB  - Lower extremity macrovascular disease is more common and progresses more rapidly
      in the presence of diabetes and has a characteristic peritibial distribution with
      sparing of the foot arteries. The biology of the diabetic foot is compromised,
      thereby making it more susceptible to injury. Hence, compromises in perfusion
      have a greater significance, warranting an aggressive approach to
      revascularization.

PMID- 9241977
TI  - After amputation. Rehabilitation of the diabetic amputee.
AB  - Rehabilitation should address the physical and psychological scars following
      ablative surgery and help the amputee plan for the future. Collaboration is
      required between the surgical team, the rehabilitation team, and social services.
      Issues of particular concern to the amputee with diabetes are discussed.

PMID- 9241978
TI  - Predicting neuropathic ulceration with infrared dermal thermometry.

PMID- 9241979
TI  - Sensory substitution in the diabetic neuropathic foot.

PMID- 9241980
TI  - In vitro excystation of metacercarial cysts of Echinostoma trivolvis from Rana
      species tadpoles.
AB  - In vitro excystation studies were done on the metacercarial cysts of Echinostoma
      trivolvis obtained from the kidneys of naturally infected Rana species tadpoles.
      Cysts were excysted in an alkaline trypsin-bile salts medium and the percentage
      of excystation was compared with that from previous studies done on cysts
      obtained from the kidneys of snails. The percentage of excystation of E.
      trivolvis metacercariae from tadpole kidneys was similar to that reported for
      previous studies on cysts obtained from experimentally infected gastropod hosts.
      The possible role of tadpoles as an agent for the transmission of Echinostoma and
      echinostomiasis to humans is discussed.

PMID- 9241981
TI  - Experimental infection of murine splenic lymphocytes and granulocytes with
      Toxoplasma gondii RH tachyzoites.
AB  - Toxoplasma gondii, an intracellular protozoan infecting many kinds of eukaryotic
      cells, has been used to experimentally infect macrophages, epithelial cells,
      fibroblasts, and various cancer cells, but rarely T and B lymphocytes or
      granulocytes. The present study was performed to determine the susceptibility of
      murine (BALB/c or CBA) splenic T and B lymphocytes, and granulocytes to infection
      with T. gondii RH tachyzoites. The ultrastructure of the infected host cells was
      observed by TEM, and the degree of intracellular parasite proliferation was
      quantified using 3H-uracil uptake assay. At 24 hrs post-culture, the host cell
      cytoplasm was found to contain 1 or 2, or a maximum of 7-8 tachyzoites. Infected
      T lymphocytes demonstrated a peripherally displaced nucleus, a parasitophorous
      vacuole enveloping the parasite, and an increased number of mitochondria. In B
      lymphocytes infected with tachyzoites, RER was not well developed compared to
      uninfected B lymphocytes. Uninfected granulocytes contained many electron-dense
      granules, but T. gondii-infected granulocytes demonstrated a decreased number of
      granules. Based on the 3H-uracil uptake assay, the susceptibility of T and B
      lymphocytes, and granulocytes, to infection with T. gondii tachyzoites was fairly
      high irrespective of cell type and strain of mouse. This strongly suggests
      deterioration in the functioning of infected host immune cells.

PMID- 9241982
TI  - Immunoblot patterns of clonorchiasis.
AB  - Clonorchis sinensis is a liver fluke which is the most prevalent helminth of
      humans in Korea. The better diagnostic measure of clonorchiasis is required for
      its nationwide control program. The present study observed antigenic bands of C.
      sinensis and reacting immunoglobulins in serum of infected residents. Adult C.
      sinensis were recovered from experimentally infected rabbits and soluble crude
      extract of the worms was used as the antigen after supplementation of E-64, a
      cysteine proteinase inhibitor. SDS-PAGE of the crude antigen resolved more than
      20 protein bands between 200 and 14 kDa. The sera of infected humans collected at
      an endemic village showed specific IgG and IgE antibodies but little IgM and IgA
      antibodies. The protein bands of 94, 80, 72, 68, 52, 47, 43, 37, 34, and 28-25
      kDa strongly reacted with serum Ig(GMA) or IgG antibody and 64, 62, 52, 47, 44,
      34, 28, and 26 kDa bands reacted with serum IgE antibody. However, the 94, 80,
      72, 68, 64, 62, 52, 47, and 40 kDa bands of C. sinensis antigen were found non
      specific. The protein bands of 43, 34, and 28-25 kDa of C. sinesis are primary
      target molecules of further analysis.

PMID- 9241983
TI  - Localization of worm antigen in Neodiplostomum seoulense by immuno
      electronmicroscopy.
AB  - The localization of worm antigen of Neodiplostomum seoulense was examined by
      immuno-electronmicroscopic observation. Not only the immunized serum of mice with
      crude worm extract of N. seoulense but also serum of infected mouse were reacted
      to the worm section. Using immunized serum as primary antibody, the gold
      particles were deposited on the rough endoplasmic reticulum of the cell of
      tribocytic organ, spermatozoa in the seminal vesicle, microvilli of the caecum
      and vitelline follicle. Using infected serum, gold particles were deposited only
      on the vitelline follicle prominently. This finding suggested that the tribocytic
      organ, seminal vesicle, caeca and vitelline follicles may play a role of antigen
      to immunized serum with crude worm extract of N. seoulense, whereas the vitelline
      follicle, to the infected serum.

PMID- 9241985
TI  - [Rapid detection of Theileria sergenti by polymerase chain reaction].
AB  - Four separate pairs of oligonucleotide primers within the coding region in a T.
      sergenti 33-kDa surface protein gene were selected to detect T. sergenti by PCR.
      The specificity of PCR-amplified DNA was examined by digestion with restriction
      enzyme and Southern blot hybridization using T. sergenti p33 DNA probe. PCR
      appears to be specific for T. sergenti, without detectable signals from
      uninfected erythrocytes, uninfected bovine leukocytes and other hemoparasites,
      including A. marginale and B. ovata. Although 46 of 71 specimens (64.8%) from
      grazing cattle were microscopically positive, PCR in this study showed that 64
      specimens (88.7%) were positive. Therefore, PCR proves a useful diagnostic tool
      for detecting T. sergenti-infected cattle. In addition, it is also revealed that
      PCR was significantly more sensitive than traditional microscopic examination
      using Giemsa's stain.

PMID- 9241984
TI  - [Cloning and sequencing of p33 in a Korean isolate of Theileria sergenti].
AB  - The gene encoding the 33 kDa piroplasm surface protein of Theileria sergenti
      isolated in Korea was cloned and the nucleotide sequence was determined by
      dideoxy chain termination method. The cloned gene corresponds to 869 bp encoding
      an open reading frame 283 amino acids. Comparison of the sequence between Korean
      and Japanese isolates showed 99.4% homology rate in the nucleotide sequence and
      98.9% homology rate in the amino acid sequence.

PMID- 9241986
TI  - Restriction endonuclease analysis of mitochondrial DNA of Acanthamoeba sp. YM-4
      (Korean isolate).
AB  - Acanthamoeba sp. YM-4 is similar to A. culbertsoni based upon morphological
      characteristics of trophozoites and cysts. However, based on other
      characteristics, pathogenicity to mice, in vitro cytotoxicity and isoenzyme
      patterns. Acanthamoeba sp. YM-4 was quite different from A. culbertsoni.
      Restriction fragment length polymorphism (RFLP) analysis of mtDNA is useful in
      the classification of members belonging to the genus Acanthamoeba. Therefore, in
      this study, RFLP analysis of Acanthamoeba mtDNAs was accomplished using five
      restriction enzymes: HaeIII, HindIII, ClaI, PvuII and SalI. Each restriction
      enzyme produced approximately 3-15 fragments (range: from 0.6 kbp to 34.4 kbp).
      The mtDNA genome size, calculated by the summation of restriction fragments,
      averaged 46.4 kbp in Acanthamoeba sp. YM-4, 48.3 kbp in A. culbertsoni and 48.8
      kbp in A. polyphaga, respectively. Digested mtDNA fragments of Acanthamoeba sp.
      YM-4 contained nine and seven same size fragments, respectively, from a total of
      67 and 69 fragments observed in A. culbertsoni and A. polyphaga. An estimate of
      the genetic divergence was 10.1% between Acanthamoeba sp. YM-4 and A.
      culbertsoni, and 9.9% between Acanthamoeba sp. YM-4 and A. polyphaga.

PMID- 9241987
TI  - [Bacterial endosymbiosis within the cytoplasm of Acanthamoeba lugdunensis
      isolated from a contact lens storage case].
AB  - Transmission electron microscopy of an Acanthamoeba isolate (KA/L5) from a
      contact lens case revealed bacterial endosymbionts within cytoplasm of the
      amoebae. The Acanthamoeba isolate belonged to the morphological group II. Based
      on the polymerase chain reaction (PCR)-restriction fragment length polymorphism
      (RFLP) of 18S ribosomal RNA coding DNA (rDNA), the isolate was identified as A.
      lugdunensis. Strain typing by isoenzyme analysis using isoelectric focusing (IEF)
      and mitochondrial (Mt) DNA RFLP revealed that the isolate was closely related
      with KA/L1, the most predominant type of isolates from contact lens storage
      cases, KA/E2, a clinical isolate, KA/W4, previously reported to host
      endosymbionts, and L3a strains of A. lugdunensis. The endosymbionts were similar
      to those of KA/W4 in aspects that they were randomly distributed in both
      trophozoites and cysts, and were rod-shaped bacteria measuring approximately 1.38
      x 0.50 microns. But the number of endosymbionts per amoeba was significantly
      lower than that of KA/W4. They were neither limited by phagosomal membranes nor
      included in lacunaelike structure.

PMID- 9241988
TI  - Intestinal pathologic findings at early stage infection by Centrocestus armatus
      in albino rats.
AB  - This study was performed to observe intestinal pathology in early infection by
      Centrocestus armatus. The flukes were in the lowermost part of the intervillous
      space of the duodenum and jejunum from 1 day to 7 days postinfection (PI). The
      stroma of villi around the young fluke was edematous and infiltrated by
      inflammatory cells such as lymphocytes, plasma cells and eosinophils. The crypt
      became mildly hyperplastic and villi were moderately atrophied at 4 days PI. The
      intestinal lesion produced was confined to the areas around the fluke. The
      pathologic findings were not significantly different between 1,000 and 5,000
      metacercariae infection groups. It is suggested that the lesion should be
      produced by mechanical destruction of the fluke on the enteroepithelial cells.

PMID- 9241989
TI  - Activities of different cysteine proteases of Paragonimus westermani in cleaving
      human IgG.
AB  - Cleaving host immunoglobulins is a well known mechanism of evading host immune
      reactions exploited by helminth parasites. Secreted cysteine proteases of
      helminth are a part of enzymes cleaving host IgG. Paragonimus westermani produces
      at least six different species of the cysteine protease in its developmental
      stages. This study was undertaken to evaluate comparatively the activities
      against human IgG by the different enzymes. When the metacercariae, which secrete
      27 and 28 kDa cysteine proteases, were incubated in human IgG solution, IgG was
      degraded at its hinge region. Further incubation resulted complete hydrolysis.
      From 4-week and 7-week old juveniles and 16-week old adults of P. westermani,
      five different enzymes at 15, 17, 27, 28 and 53 kDa have been purified, if the
      enzyme with the same molecular mass is regarded to be identical. In cleaving
      human IgG, each cysteine protease exhibited decreasing activities with age.

PMID- 9241990
TI  - Hookworm: not a pre-Columbian pathogen.
AB  - It has been asserted that evidence of pre-Columbian hookworm has been found in
      the Americas, specifically in Peru, Brazil, and Tennessee. However, based on an
      analysis of the life cycle and morphology of hookworm, the paleopathologic
      indications for the presence of hookworm infestation in the Americas prior to
      1492 are suspect. It is concluded that the material found in the Peruvian mummy
      is probably pinworms, that the Brazilian and Tennessee materials are probably not
      hookworm, and, therefore, that hookworm was one of many pathogens brought to the
      Americas after contact in 1492.

PMID- 9241991
TI  - A therapy to live by: public health, the self and nationalism in the practice of
      a north Indian yoga society.
AB  - In this article I focus on the relationship between concepts of self and health
      in modern North India. Drawing on field research in a popular yoga society, I
      argue that yoga therapy, as practiced by the Bharatiya Yog Sansthan of Delhi,
      provides a reconceptualization of what can be meant by public health. Using
      studies that challenge both the essentialist and epistemological facticity of the
      self, I show how the discourse and practice of yoga is implicated in, and derived
      from, a complex search for self definition in terms of health; health which is
      conceived of as a public regimen that seeks to reconnect that which modernity has
      broken apart: mind and body.

PMID- 9241993
TI  - Infect one, infect all: Zulu youth response to the AIDS epidemic in South Africa.
AB  - The province of KwaZulu-Natal leads South Africa in HIV/AIDS infection, with over
      two-thirds of the currently estimated 1.8 million cases. Recent studies show that
      the spread of HIV is accelerating, especially among young people under the age of
      25. For Zulu township youth, HIV infection has come to be accepted as a new and
      inevitable part of growing up. Ongoing political violence and high levels of
      crime characterize the townships, from which has emerged a youth culture where
      young people who suspect they may be infected with HIV will avoid a definite
      diagnosis while at the same time seek to spread the infection as widely as
      possible. This response to the growing HIV/AIDS epidemic is examined against the
      cultural ethos of ubuntu and the strategies once used by youth to forge
      solidarity in their struggle against the former white regime. The social impact
      of this response, which may include increasing rape incidence, is discussed.

PMID- 9241992
TI  - Purity and passion: risk and morality in Latina immigrants' and physicians'
      beliefs about cervical cancer.
AB  - This paper examines how physicians' beliefs about risk factors for cervical
      cancer compare with Mexican and Salvadoran immigrant women's views (hereafter
      Latina immigrants). Between August 15, 1991 and August 15, 1992, we conducted
      ethnographic interviews with 39 Mexican immigrant women, 28 Salvadoran immigrant
      women, and 30 physicians in northern Orange County, California. Physicians and
      Latina immigrants converge on their beliefs that sexual behavior is a predominant
      risk factor for cervical cancer. They diverge, however, on their reasons. Latina
      immigrants' perceptions of health risks are embedded in a larger set of cultural
      values centering around gender relations, sexuality, and morality. Latina
      immigrants also emphasized men's behavior as risk factors. Physicians' views, on
      the other hand, are largely based on the epidemiology of cervical cancer risk
      factors. They emphasized beginning sexual relations at an early age, multiple
      sexual partners, and infection with sexually transmitted viruses. Some
      physicians, however, displayed moral interpretations of the sex-based risk
      factors for cervical cancer through the use of the culturally-loaded term
      "promiscuous" in place of "multiple sexual partners," through specific references
      to morality, and through characterizations of women at risk for cervical cancer.
      Both the physicians and the Latina immigrants in our study paid considerably less
      attention to socioeconomic factors. Our results have important implications for
      physicians who provide health care for Latina immigrants. Physicians should be
      clear to point out that women need not be "promiscuous" to get cervical cancer.

PMID- 9241994
TI  - The human growth hormone Creutzfeld Jakob disease litigation.

PMID- 9241995
TI  - A perspective on complementary medicine.

PMID- 9241996
TI  - Limitation and medical negligence.

PMID- 9241997
TI  - Appointment of the coroner.

PMID- 9241998
TI  - Development of a primary health care information system in Ghana: lessons
      learned.
AB  - In Ghana, between January 1990 and September 1993, a series of steps were
      undertaken to review the existing vertical reporting procedures and to develop an
      integrated Health Management Information System (HMIS) for Primary Health Care
      (PHC). These steps included a situation analysis of the existing reporting
      systems; participatory design of tools for planning, data collection, feedback
      and reporting; field test and revision of the modified system; training of staff
      at all levels; development of tools for self-assessment and stimulation of
      routine feedback to lower levels and reporting of analysed indicators to higher
      levels. There were some notable achievements which included promotion of self
      reliance, improved data relevance and accuracy, as well as strengthened
      supervision and support. However, it was difficult to identify the most
      appropriate institutional location for the HMIS; over-emphasis on process leads
      to reduced implementation; reporting was still given greater priority than
      analysis and use of data, and systems for collection and use were still
      cumbersome and time consuming. It is also difficult to prove that having better
      information really improves decision-making, or even coverage and quality of PHC
      service delivery. These issues, as well as lessons learned, are discussed in the
      paper.

PMID- 9241999
TI  - Health-care technology transfer: expert and information systems for developing
      countries.
AB  - Computer-based technologies such as information systems and expert systems have
      an undoubted contribution to health-care development in developing countries.
      This paper addresses the appropriateness of these technologies for developing
      countries, the criteria to be used in selection of the technology to be
      transferred, and the need for a systematic approach to evaluation. A conceptual
      model for assessing transferability so as to achieve an effective transfer, has
      been introduced. This requires not only an attempt to amplify the role of
      information and expert systems in health-care improvement and for socio-economic
      development, but the analysis of prior experience in transferring these
      technologies to developing countries. Following this approach, and using
      operational research techniques such as the Analytic Hierarchy Process, a
      subjective assessment model has been described that can systematically guide
      decision-making about computer-based health-care technology to be transferred to
      developing countries.

PMID- 9242000
TI  - Health informatics: handle with caution.
AB  - The increased use of computers is a response to the considerable growth in
      information in all fields of activities. Related to this, in the field of
      medicine a new component appeared about 40 years ago: Medical Informatics. Its
      goals are to assist health care professionals in the choice of data to manage and
      in the choice of applications of such data. These possibilities for data
      management must be well understood and, related to this, two major dangers must
      be emphasized. One concerns data security, and the other concerns the processing
      of these data. This paper discusses these items and warns of the inappropriate
      use of medical informatics.

PMID- 9242001
TI  - Decision support systems in health care.
AB  - This paper delineates the application of decision support systems in the
      healthcare arena. An overview of decision support systems in the healthcare
      environment in the last three to five years, mostly in the USA and the UK is
      provided. Some reference is made to work in South Africa. Although this report
      endeavours to emphasise the decision support system side, some operations
      research issues are also addressed. This paper is divided into several sections:
      decision support systems definition, techniques used, the use of operations
      research in specific areas of healthcare, information systems, assessment of
      decision support systems, in-house development, decision support in South Africa
      and future of decision support systems.

PMID- 9242002
TI  - Health-2000: an integrated large-scale expert system for the hospital of the
      future.
AB  - Decision making and management are problems which plague health systems in
      developing countries, particularly in Sub-Saharan Africa where there is
      significant waste of resources. The need goes beyond national health management
      information systems, to tools required in daily micro-management of various
      components of the health system. This paper describes an integrated expert
      system, Health-2000, an information-oriented tool for acquiring, processing and
      disseminating medical knowledge, data and decisions in the hospital of the
      future. It integrates six essential features of the medical care environment:
      personnel management, patient management, medical diagnosis, laboratory
      management, propharmacy, and equipment management. Disease conditions covered are
      the major tropical diseases. An intelligent tutoring feature completes the
      package. Emphasis is placed on the graphical user interface to facilitate
      interactions between the user and the system, which is developed for PCs using
      Pascal, C, Clipper and Prolog.

PMID- 9242003
TI  - Fundamentals of modern telemedicine in Africa.
AB  - The FOMTA (Fundamentals of Modern Telemedicine in Africa) project aims to promote
      the development of indigenous regional networks between R&D centres and
      universities of the Developing Countries (DCs) and their European counterparts.
      While FOMTA prepares the way for the use of broadband technology in Africa, it
      will also associate the DCs with the generation of knowledge, innovative and
      appropriate technologies needed to solve some of the specific problems, in order
      to achieve a sustainable economic development. Designed to eliminate the time
      delaying lack of infrastructure, FOMTA will embark on the simulation of the
      integrated Service Digital Network infrastructure. FOMTA will adopt measures to
      increase the awareness and stimulate the participation of the DCs in the
      telemedicine and health care telematics projects through demonstrations, pilot
      projects, workshops, training and exchange activities. This will demonstrate the
      feasibility of telemedicine services in the DCs, including trial of services in
      real-life circumstances, and will provide training possibilities for researchers
      in the use of methods and tools for advanced communication technologies and
      telematics. Undoubtedly, telediagnosis, teleconsultation and other areas of
      telemedicine would thrive in Africa both as remote testing grounds and fields of
      practical applications.

PMID- 9242004
TI  - National health management information system: issues of funding and support.
AB  - Information Technology has made a substantial inroad into Nigerian society,
      particularly since the late 1980s. It is, however, already being applied in the
      health sector. The Obafemi Awolowo University Teaching Hospitals Complex
      (OAUTHC), lle-lfe, Nigeria has adopted a systematic approach to the development
      of a Health Information System (HIS) for a typical specialist hospital. A review
      of the existing HIS in OAUIHC is presented, highlighting its attributes,
      problems, and limitations. In addition, the options of funding HIS on a national
      scale are identified and discussed. Finally, strategies to ensure ongoing support
      of a national HIS are presented.

PMID- 9242005
TI  - Supporting multi-level medical education with knowledge-based systems.
AB  - Knowledge-based systems for medicine have enjoyed minimal success in developing
      countries as end-user systems. The reasons for this are complex. As funding
      agencies understandably tend to err on the side of caution, and knowledge-based
      systems are still (despite an almost 40 year history) seen as a new and untried
      technology, few have been implemented. Of those which have, most are
      inappropriately simple and thus do not fit in with the real-life clinical
      environment. In contrast to the sophisticated systems in use in developed
      countries which reflect a mature technology, the use of knowledge-based systems
      in medicine in developing countries has primarily revolved around simple 'expert'
      systems, where the program functions more as a 'guru' than as a support function.
      We propose the more appropriate use of these systems as educational tools in
      medicine. In this discussion paper we describe a multi-level programme to support
      medical education, focusing on patient information systems involving natural
      language generation, decision-support systems as educational aids for primary
      health-care workers and model-based reasoning tools which allow exploratory
      learning for physicians in training. Throughout this paper we refer to Knowledge
      Based Medical Education Systems as KBMES.

PMID- 9242006
TI  - Extended telemedical consultation using Arden Syntax based decision support,
      hypertext and WWW technique.
AB  - There is an obvious need for geographic distribution of expert knowledge among
      several health care units without increasing the cost of on-site expertise in
      locations where health care is provided. This paper describes the design of a
      knowledge-based decision-support system for extended consultation in clinical
      medicine. The system is based on Arden Syntax for Medical Logic Modules and
      hypertext using World Wide Web technology. It provides advice and explanations
      regarding the given advice. The explanations are presented in a hypertext format
      allowing the user to browse related information and to verify the relevance of
      the given advice. The system is intended to be used in a closed local network.
      With special precautions regarding issues of safety and patient security, the
      system can be used over wider areas such as in rural medicine. A prototype has
      been developed in the field of clinical microbiology and infectious diseases
      regarding infective endocarditis.

PMID- 9242007
TI  - District level information systems: two cases from South Africa.
AB  - The health system in South Africa has to date been fragmented and centralised.
      The priority of the new government is to establish an integrated and
      decentralised district health system of which a key element is the development of
      district health and management information systems (H & MIS). This paper presents
      experiences from two projects in the Western Cape in which a process to establish
      a district-based H & MIS was initiated and a situation analysis of the
      information systems was done. The two projects applied different research methods
      but the results show with remarkable consistency that much time is used on data
      collection, but information is not used at local level. The projects have applied
      different approaches towards developing a district H & MIS but in both important
      pre-requisites for a successful, action-led H & MIS include local ownership and
      motivation, a process based around existing local management structures and the
      active involvement of the community.

PMID- 9242008
TI  - A computerised implementation of a minimum set of health indicators.
AB  - Three alternative approaches to computerise primary health care services as
      provided in clinics in South Africa are compared. The first approach implements a
      system based on a head-count approach using a minimum set of indicators. This
      system resembles the current manual system of tally sheets. The second and third
      approaches implement computer systems based on patient records. The second
      approach is based on a very limited data set, and the third utilizes a
      comprehensive demographic and clinical data set. The three alternatives are
      compared with regard to practicality, flexibility, ease of use, accuracy and
      completeness of statistical reports, and time utilisation. It is concluded that
      the flexibility of a patient-record approach, although more time consuming, is
      preferred. The second alternative is more feasible in a developing country with
      mostly computer-illiterate nurses. Ways in which such a system can be implemented
      in an environment with limited hardware resources are also proposed.

PMID- 9242009
TI  - Philosophy into practice: a health informatics course proposal.
AB  - International health informaticians acknowledge the critical importance of
      education and training to the successful implementation of information technology
      in the health-care setting. As access to the Internet grows, so does the richness
      of resources the Internet can supply. With the changes in health care brought by
      communication, telematics will become the successor to informatics. The authors
      present the philosophy of telematics training and propose a short training course
      designed to help health professionals in developing nations take advantage of
      telematics, providing conceptual understanding and hands-on training.

PMID- 9242011
TI  - Fault diagnosis in an expert system for health services management in the
      tropics.
AB  - An integrated large-scale expert system called Health-2000, for the management of
      health services in regions where tropical diseases are endemic, has been
      designed. This system combines knowledge and databases, the contents of which are
      operated upon by an inference engine, to produce usable information. The system
      allows a host of applications, ranging from medical diagnosis to fault detection
      and preventive maintenance of biomedical equipment. The theoretical background
      and approach used in the development of the fault diagnosis and equipment
      maintenance sub-system of Health-2000 is presented. Model-based knowledge
      acquisition, and an extension of the Failure Modes, Effects and Criticality
      Analysis are two methodologies applied to build its knowledge bases. The
      inference engine which supports backward and forward chaining, operates on
      numerical and non-numerical facts, and uses fuzzy logic to handle vague and
      uncertain knowledge. Fault isolation proceeds in a top-down fashion, from
      equipment sub-system, to modules and components.

PMID- 9242010
TI  - A philosophy for health informatics education in developing countries: Nigeria as
      a case study.
AB  - The use of computers in the health sector has increased significantly during the
      last few years in Nigeria. This paper addresses the integration of health and
      informatics education, or health education and informatics education, or
      informatics education in health care delivery. It gives an introduction to the
      status of a health informatics programme in the daily practice of computer use.
      The essence of a health informatics curriculum, the planning and administration
      of the programme in medical schools, and what informatics education offers the
      health sector, even in a developing country, are presented. The problems of
      administering an informatics programme in a conventional medical training
      curriculum are highlighted. The article describes the philosophy which should
      underline the framework for the formulation of appropriate national policies and
      curricula for health informatics education in developing countries, using Nigeria
      as a case study.

PMID- 9242012
TI  - User attitudes to a heritage hospital information system.
AB  - A heritage system is one that has exceeded its lifespan but continues to be used
      for various reasons, despite the problems it may be causing. Groote Schuur
      Hospital has a Hospital Information System that is more than 25 years old. The
      present study reports the result of a survey on users' attitude and sense of
      involvement in this system. An attempt is made to determine whether users feel
      the need for change and whether a sense of involvement is related to this need.

PMID- 9242013
TI  - Role of an effective hospital information system in a depressed economy.
AB  - This work is based on practical experience acquired in the development of a
      hospital information system in a university hospital in Nigeria. The paper
      discusses how accurate, adequate and timely medical data can promote economy in
      health-care delivery in a depressed economy. Existing constraints are identified
      and solutions offered for an effective hospital information system. An effort has
      been made to illustrate how the application of informatics technology can be cost
      effective in the long-term, by ensuring effective and economic use of facilities
      and resources. Once an effective hospital information is operative, provision of
      affordable health care in a depressed economy would be feasible. To this end, the
      need for cooperation between countries to support technology and manpower is
      emphasized.

PMID- 9242014
TI  - Development of an HIV clinical and research database for South Africa.
AB  - Health service restructuring in South Africa provides an opportunity to introduce
      appropriate Health Information System (HIS) technology. This is particularly
      relevant given the emerging HIV epidemic and the need to capture, translate and
      disseminate new experiences in HIV/AIDS care, support and clinical research. In
      1994, a number of clinicians and health-care providers working in South Africa
      had begun to establish basic computerized databases to assist in research on HIV,
      but no standardized nomenclature or framework for collaboration was created. This
      paper describes a clinical and research database that could be used as an example
      for a standardized system by clinicians working in South Africa. The authors,
      with assistance from the National AIDS Research Programme of the Medical Research
      Council, created a prototype relational database using Microsoft Access. To test
      the prototype, 1057 HIV-positive patients from the infectious Disease Clinic at
      Johannesburg General Hospital were entered.

PMID- 9242016
TI  - The use of knowledge-based systems in medicine in developing countries: a luxury
      or a necessity?
AB  - Knowledge-based systems (KBSs) in medicine have received much attention over the
      past two decades, mainly because of the potential benefits that can be gained
      from using them. They may facilitate in increasing productivity in a medical
      environment, support the making of diagnoses and other types of medical
      decisions, assist in the training of medical professionals, and can even handle
      some routine tasks in a medical environment. However, some critical problems in
      this field have also been identified. For example, research indicated that some
      problems can be solved partially, but not completely, with existing artificial
      intelligence techniques. Another problem is that many of the existing medical
      information systems do not support the integration of KBSs in a natural way.
      Furthermore, the routine use of a medical KBS is complicated by legal issues.
      These and other problems contribute to what we experience today: a large
      proportion of the medical KB applications that are developed is never actually
      used in practice. This justifies questions such as: Should developing countries,
      having limited infrastructure and research resources, invest in medical KBSs
      research and development, or should this field be regarded as a luxury that only
      belongs to developed countries?, and: Can developing countries really benefit
      from the use of these systems? These questions are discussed in this paper. We
      highlight the main problems surrounding the development and use of medical KBSs.
      With the focus on developing countries we discuss potential benefits that could
      be obtained by investing in these systems and we offer guidelines for focusing
      research and development of medical KBSs.

PMID- 9242015
TI  - Computer-based training and electronic publishing in the health sector: tools and
      trends.
AB  - CBT (computer-based training) applications and hypermedia publications are two
      different approaches to the utilisation of computers in medical education.
      Medical CBT software continues to play a minor role in spite of the increasing
      availability, whereas hypermedia have become very popular through the World Wide
      Web (WWW). Based on the HTML format they can be designed by non-programmers using
      inexpensive tools while the production of CBT applications requires programming
      expertise. HTML documents can be easily developed to be distributed by a web
      server or to run as local applications. In developed countries CBT and hypermedia
      have to compete with an abundance of printed or audio-visual media and a wealth
      of lectures, conferences, etc., whereas in developing countries these media are
      scarce and expensive. Here CBT programs, and hypermedia publications in
      particular, may be a cost-effective way to improve quality of education in the
      health sector.

PMID- 9242017
TI  - Extraction of rules for tuberculosis diagnosis using an artificial neural
      network.
AB  - The treatment of tuberculosis (TB) is a major challenge throughout the world. The
      Western Cape Region of South Africa has the highest occurrence of TB in the
      world. Here, TB is increasing due to improperly managed treatment programmes and
      inadequate facilities. The development of rules to aid medical practitioners in
      the early and accurate diagnosis of tuberculosis should prove worthwhile. A
      method to extract such diagnostic rules from an artificial neural network is
      presented. These rules accurately represent the knowledge embedded in the "raw"
      TB data.

PMID- 9242018
TI  - A call to action.

PMID- 9242019
TI  - Direct access to ob/gyns is about women, not turf.

PMID- 9242020
TI  - Mission possible.

PMID- 9242021
TI  - A letter from Tanzania.

PMID- 9242022
TI  - Child labor: the impact of economic exploitation on the health and welfare of
      children.

PMID- 9242024
TI  - A heartening exchange.

PMID- 9242023
TI  - International medicine: outside the comfort zone.

PMID- 9242026
TI  - Minnesota delegation proposes tobacco resolution.

PMID- 9242025
TI  - Sterilization for family planning in a Third World country.
AB  - Outpatient laparoscopy procedures have made sterilization possible for millions
      of women in developing countries. This report describes the experience of a team
      of doctors, nurses, and support staff that performed 107 laparoscopic tubal
      sterilizations during on eight-day sojourn in a remote north-central area of
      Nicaragua. Minimal analgesia (oral ibuprofen) and anesthesia (1% lidocaine) were
      used since most of the patients walked to and from the hospital-some up to 15
      miles. Because the Nicaraguan government's support for birth-control programs is
      unreliable and because illegal abortion is the leading cause of maternal
      mortality in Nicaragua, this safe, minimally invasive surgical method is the
      favored means of birth control.

PMID- 9242027
TI  - Minnesota enacts patient protections.

PMID- 9242028
TI  - Human Rights Foundation of Turkey seeks MMA support.

PMID- 9242029
TI  - Health at work.

PMID- 9242030
TI  - The dancing plague: a public health conundrum.
AB  - The phenomenon of mass, frenzied dancing affected large populations in various
      parts of Europe from the thirteenth century and lasted, on and off, for three
      centuries. The exact aetiology of the Dancing Plague (or Dancing Mania) is still
      unclear. Retrospective historical review of this public health problem reveals
      claims for causative factors including demonic possession, epilepsy, the bite of
      a tarantula, ergot poisoning and social adversity. It seems unlikely that Dancing
      Mania resulted from a single cause but rather resulted from multiple factors
      combining with a predisposing cultural background and triggered by adverse social
      circumstances. Dancing Mania remains one of the unresolved mysteries of public
      health.

PMID- 9242031
TI  - HIV/AIDS infection control enforcement: a comparison between Nigeria and the
      United States.
AB  - We examined differences in approaches to HIV-related infection control practices
      in two university teaching hospitals in the United States and Nigeria. Health
      care workers (n = 202 in Nigeria and 186 in the USA) responded to a previously
      validated measure of infection control practices. There were significant
      differences in the estimated probability of treating a person with HIV disease
      (higher in USA), and a greater probability of peer ridicule as a way of enforcing
      group norms on infection control in Nigeria. Peer enforcement of norms was
      significantly lower in the USA. In both countries, more precautions would be
      taken if it was known that the patient was HIV infected. Infection control
      practices were more likely to be followed in the USA compared with Nigeria if
      they were praised for this activity, if appropriate facilities (sharps
      containers, gloves, etc.) were nearby, and if they felt that infection control
      procedures were effective. These data point to the importance of normative social
      pressures in Nigeria and of knowing the patient is HIV infected in the USA and
      feeling that infection control procedures are effective ways of avoiding
      occupational HIV infection. The role of normative pressures and assumptions about
      HIV infection status as well as cues and availability of facilities for infection
      control appear to differ between these health care workers in Nigeria and the
      USA.

PMID- 9242032
TI  - Tropical illness profiles: the psychology of illness perception in Malawi.
AB  - Psychological and social investigations of tropical diseases can make a
      significant contribution to understanding and managing many illnesses. One
      hundred and seventy-five Malawian university students rated peopled who suffered
      from AIDS, malaria, schistosomiasis and the 'common cold', on 11 psycho-social
      dimensions related to illness. Analysis of variance and factor analysis was used
      to distinguish distinctive illness profiles reflecting perceptions of (people
      with) these illnesses. Results suggested that infirmity was associated with AIDS
      and that the seriousness of malaria was minimized. Within a context of many
      threats to health the importance of distinguishing between serious illnesses is
      emphasized for effective health promotion interventions.

PMID- 9242033
TI  - Population density and cancer mortality by gender and age in England and Wales
      and the Western World 1963-93.
AB  - The aetiology of malignant disease is multi-factorial, including contributory
      environmental factors. Based upon the premise that increases in the density of
      population will be coterminous with a worsening of the environment, it is
      hypothesised that such changes should be reflected in an increase in cancer
      mortality in general and in elderly populations. By focusing upon changes in the
      elderly (+75) deaths between two time periods, the study corrects for age factors
      related to cancer mortality. The study tests this hypothesis via correlations
      between population density and malignancy death rates in general and elderly age
      bands over a thirty year period. It was found that there were positive and
      significant correlations between population density and malignancy mortality
      rates in the Western World, especially amongst men, but all correlations
      strengthened in the direction hypothesised. The findings were not an artefact of
      longevity, further research is required to give a better understanding of these
      findings.

PMID- 9242034
TI  - Emergency medical admissions to hospital--the influence of supply factors.
AB  - A retrospective review of all adult medical in-patient hospital records in one
      health district (adult population 378,000) was performed over three consecutive
      years. Yearly age-standardised rates for emergency admissions were calculated and
      compared between sections of the population with differing access to hospital
      beds. Confounding and other explanatory variables were examined with a logistic
      regression model. Emergency medical admission rates were consistently higher in
      the population whose general practitioner had access to community hospital beds,
      as compared with those whose general practitioner had no access, (46.1 per
      thousand population vs 39.3 per thousand in the year 1994-95, difference
      significance, P < 0.05). Multivariable analysis suggests that in addition to
      supply factors, age, sex, morbidity and socio-economic circumstance influence
      admission rates.

PMID- 9242035
TI  - British agencies for adoption and fostering in Scotland--Scottish Medical
      Advisers' survey.
AB  - Children in local authority care (The survey was conducted before the term 'in
      care' was replaced by 'looked after' on The Children (Scotland) Act coming into
      force in October 1996) come from backgrounds of high incidence of mental illness,
      substance abuse and learning difficulties and have often suffered from neglect
      and/or abuse. They have a high incidence of medical problems affecting both
      physical and mental health. The Committee of the Scottish Section of the Medical
      Group of British Agencies for Adoption and Fostering (BAAF) were concerned about
      the provision and co-ordination of medical services for children in local
      authority care. The aim of the survey was to identify the current and evolving
      practice among medical advisers across Scotland. Questionnaires were returned
      from 40 Medical Advisers representing each of the local authorities in Scotland.
      The responses highlighted a variation in the implementation of practice in
      clinical services provided to children in care and by whom. It confirmed that
      difficulties in follow-up did exist and revealed widespread confusion surrounding
      co-ordination of medical services, absence of procedures and ignorance of legal
      requirements. The study confirms that involved medical practitioners need to have
      a pro-active role in co-operating closely with social work colleagues to provide
      a well co-ordinated service of medical supervision providing a comprehensive
      assessment of health care needs as part of the overall child care plan.

PMID- 9242036
TI  - The impact of heart health promotion on coronary heart disease lifestyle risk
      factors in schoolchildren: lessons learnt from a community-based project.
AB  - A community health promotion project called Action Heart was undertaken in two
      electoral wards in Rotherham to try to change lifestyles of people. Schools were
      included within the project. Coronary heart disease lifestyle risk factors were
      measured at baseline and after a three year period in the intervention area and a
      similar control area. Lifestyle factors in schoolchildren were measured
      separately from adults using a different instrument. The post intervention survey
      of adults and economic evaluation demonstrated that Action Heart had achieved
      cost-effective estimated health gains. In the schoolchildren however, a mixture
      of positive and negative risk factor changes in both areas was demonstrated.
      Significant changes in lifestyle risk factors in schoolchildren were not elicited
      using this approach. The possible reasons for the lack of impact on lifestyle
      risk factors in schoolchildren are examined and the implications for further work
      explored.

PMID- 9242037
TI  - The associations between feeding modes and diarrhoea among urban children in a
      newly developed country.
AB  - The protective effect of breastfeeding against infantile diarrhoea may be less
      pronounced in areas with modern water supply and sanitation facilities. This
      finding raises the question whether protection by breastfeeding against infantile
      diarrhoea in developing countries will decline with improvement in water supply
      and sanitation. To address this question a historical cohort study of the
      associations between feeding modes and diarrhoea incidence and severity in
      children aged 0-14 months at baseline was done in Al Ain city, United Arab
      Emirates. In this city in a newly developed country, modern water supply and
      sanitation facilities have become available to everyone during the last two
      decades. During three months of follow-up of 249 children, the nonbreastfed had
      more diarrhoea than did the partly breastfed, who in turn had more diarrhoea than
      did the fully breastfed. After multivariate adjustment, this dose-response effect
      was consistent for three measures of diarrhoeal morbidity in each child:
      occurrence or non-occurrence of incidence episodes, number of episodes, and total
      severity score. However, significant differences were seen only between the
      nonbreastfed and fully breastfed subgroups. These results indicate that in Al
      Ain, despite the universal access to modern water supply and sanitation
      facilities, breastfeeding plays an important role in reducing the incidence and
      severity of infantile diarrhoea. This observation is particularly important given
      the growing concern that, as an unwanted effect of 'modernisation', breastfeeding
      is on the decline in Al Ain and comparable populations elsewhere.

PMID- 9242038
TI  - Effect of vitamin A supplementation on measles vaccination in nine-month-old
      infants.
AB  - OBJECTIVE: Childhood immunization programs have been suggested as an
      infrastructure to deliver vitamin A supplements to children in developing
      countries. The effects of giving vitamin A, a potent immune enhancer, with
      measles immunization to nine-month-old infants is unknown. METHODS: A randomized,
      double-masked, placebo-controlled clinical trial of vitamin A, 100,000 IU at the
      time of standard titer Schwarz measles immunization was conducted with nine-month
      old infants in Bogor District, West Java, Indonesia. Antibody titers to measles
      were measured at baseline and one and six months following immunization. RESULTS:
      394 infants received measles immunization, and 37 infants (9.4%) had baseline
      antibody titers > 1:120, which is consistent with previous natural measles
      infection. Of the remaining infants, 98.8% seroconverted to measles, and 99.3%
      had titers consistent with protection against measles six months
      postimmunization. Seroconversion rates were similar in vitamin A and placebo
      treatment groups. CONCLUSION: High dose vitamin A supplementation can be given
      without reducing seroconversion to standard titer Schwatz measles immunization in
      nine-month-old infants.

PMID- 9242039
TI  - Tinea pedis outbreak in swimming pools in Japan.
AB  - This study was conducted to show a higher prevalence of interdigital tinea pedis
      in athletes by comparing athletes and non-athletes, and to examine swimming pools
      as a route of infection. The subjects were 282 athletes, 137 non-athletes, and
      140 students enrolled in a swimming class at the University of Tsukuba. This
      study included the taking of cotton-swab samples from the interdigital skin
      surfaces of both feet and cultures, microscopical examinations of scales
      collected from subjects with lesions, and questionnaires. There was a significant
      difference between athletes and non-athletes in the prevalence of the relevant
      pathogens, and a higher risk of infection was shown in athletes. The study also
      found that 63.6% of the swimming class students were carriers, and that 85.0% of
      their dermatophytes were Trichophyton mentagrophytes. In addition, dermatophytes
      were also isolated from the floors of the swimming pool and the public baths. The
      results of these controlled studies suggested that there was a significant risk
      of dermatophytosis in both athletes and non-athletes using the swimming pool.

PMID- 9242040
TI  - Do CuSums have a role in routine communicable disease surveillance?
AB  - The swift identification of outbreaks of infection is essential for effective
      control in the population. One of the functions of surveillance is to detect
      outbreaks but it could be argued that this is one of the weaker aspects of
      routine surveillance at present. This paper describes a technique which might
      meet this surveillance need. The CuSum technique allows rapid measurement of
      change from expected values based on historical data. It is very simple and seems
      to be a highly sensitive technique which can signal the need for further scrutiny
      of the data and/or for public health action, long before a change in incidence is
      apparent from raw data. This is particularly true for low-incidence infections
      where large functions can make interpretation difficult. CuSums represent a
      potentially useful adjunct to other surveillance methods in infection control.

PMID- 9242041
TI  - Consequences of analysing complex survey data using inappropriate analysis and
      software computing packages.
AB  - In the analysis of complex survey data such as stratified multi-stage cluster
      samples, ignoring the design effects such as clustering and stratification
      usually will lead to erroneous conclusions. In this paper, we will demonstrate
      the consequences in the estimation of means and proportions by two examples from
      a stratified two-stage cluster sample. A brief review of methodology will be
      presented, and some suggestions on computational issues will be provided.

PMID- 9242042
TI  - Netrins evoke mixed reactions in motile cells.

PMID- 9242043
TI  - Phenotypic analysis--making the most of your mouse.

PMID- 9242044
TI  - The APC tumor suppressor protein in development and cancer.

PMID- 9242045
TI  - DNA on the move.

PMID- 9242046
TI  - Expanding DNA advancing.

PMID- 9242047
TI  - Viral nucleic acid sequence transfer between fungi and plants.

PMID- 9242048
TI  - Of mice and (mad) cows--transgenic mice help to understand prions.
AB  - Prions present a most fascinating biological conundrum. These proteinaceous
      particles seem to propagate through a chain reaction in which a host protein,
      PrPC, is post-translationally misfolded to form new prions. By this mechanism
      they 'replicate' without involvement of specific nucleic acids. Due to their
      unique modus operandi, prions cause disorders that can be infectious, inherited
      and sporadic. Transgenetics has been invaluable in helping to understand this
      unique phenomenon. Here we describe some of the most salient contributions of
      transgenic mice to this field.

PMID- 9242049
TI  - Preimplantation genetic diagnosis: strategies and surprises.
AB  - Several inherited diseases can now be diagnosed by genetic analysis of single
      cells biopsied from human eggs and preimplantation embryos following in vitro
      fertilization (IVF). 'At risk' couples can, therefore, have only unaffected
      embryos replaced in the uterus and avoid the possibility of terminating a
      pregnancy that might only be diagnosed as affected later is gestation. Single
      cell genetic analysis has also provided powerful tools for studying genetic
      defects arising during early human development. Recent studies of cleavage-stage
      human embryos have revealed an unexpectedly high incidence of postzygotic
      chromosomal abnormalities, which might arise because of a lack of cell-cycle
      checkpoints before the embryonic genome is activated. These genetic abnormalities
      are likely to contribute to early pregnancy loss and have important implications
      for improving pregnancy rates in infertile couples by assisted reproduction.

PMID- 9242050
TI  - Cellular and molecular biology of neural crest cell lineage determination.
AB  - The past few years have seen an explosion of information about genes that control
      the development of the neural crest, a structure unique to vertebrate
      embryogenesis. Many of these genes are mutated in human diseases that affect
      crest-derived lineages. At the same time, decades of work on the neural crest at
      the cellular level are generating new insights into the segregation of different
      lineages and the role played by environmental signals in the lineage-commitment
      process. The challenge now is to integrate the cellular and molecular genetic
      perspectives on neural crest development. This review attempts such a synthesis.

PMID- 9242051
TI  - Origin of genes encoding multi-enzymatic proteins in eukaryotes.
AB  - In several biosynthetic pathways of eukaryotes, multiple steps are catalyzed by
      enzymes physically linked as domains of multi-enzymatic proteins. The same steps
      in prokaryotes are frequently carried out by mono-enzymatic proteins. If genes
      encoding mono-enzymatic proteins are the precursors to those genes encoding multi
      enzymatic proteins, how these genes fused remains an open question. However, the
      recent discovery of a cleavage-polyadenylation signal within an intron of the
      GART gene provides clues to this process and might also have more general
      implications for the origin of genes that contain alternative RNA processing
      reactions at their 5' or 3' ends.

PMID- 9242052
TI  - How to limit your sequence search by organism.

PMID- 9242053
TI  - How big should that raise be?

PMID- 9242054
TI  - Doctor, is your hygiene department profitable.

PMID- 9242055
TI  - Stop and consider patient satisfaction.

PMID- 9242056
TI  - Document your practice.

PMID- 9242057
TI  - Together we stand, divided we fall.

PMID- 9242058
TI  - Dentists respond to annual practice survey.

PMID- 9242059
TI  - The credit and collection game.

PMID- 9242061
TI  - Secret weapons: why dentists aren't super successful.

PMID- 9242060
TI  - Who will inherit your IRA?

PMID- 9242062
TI  - Hiring and retaining associates.

PMID- 9242063
TI  - Office of the month. Office of the northwoods.

PMID- 9242064
TI  - My insurance company says you charge too much!

PMID- 9242065
TI  - Restructure your team to share management responsibilities.

PMID- 9242066
TI  - How to develop an esthetic-centered practice.

PMID- 9242067
TI  - Integrating cosmetic dentistry into a busy practice.

PMID- 9242068
TI  - Efficient scheduling.
AB  - Schedule doctor and assistant time separately. The dentist should be clearly
      scheduled in the proper operatory for that part of the procedure only he can do,
      not double-scheduled. At any given time, an assistant should be with the other
      patient, providing services and customer service. This relieves a tremendous
      amount of stress, increases productivity and allows the practice to run far more
      efficiently.

PMID- 9242069
TI  - What do you mean you don't need an intraoral camera?

PMID- 9242070
TI  - Communicating with your patients.

PMID- 9242071
TI  - Are we violating patient trust through poor time management?

PMID- 9242072
TI  - Commitment levels.

PMID- 9242073
TI  - The unseen practice-builder.

PMID- 9242074
TI  - The credit connection.

PMID- 9242075
TI  - How, when and why to write off an account.

PMID- 9242076
TI  - Staff salaries continue to rise, but employee numbers level.

PMID- 9242077
TI  - It's not what you say, it's how you say it.

PMID- 9242078
TI  - Office of the month. Location makes the difference.

PMID- 9242079
TI  - Barbarians at the gape!

PMID- 9242080
TI  - Read the fine print!

PMID- 9242081
TI  - The dental net.

PMID- 9242082
TI  - The lost patient syndrome.

PMID- 9242083
TI  - Achieve a successful dental-practice transition.

PMID- 9242085
TI  - Designing your reception room.

PMID- 9242084
TI  - Retirement plans: six ways to reduce staff funding costs.

PMID- 9242086
TI  - Is your Yellow Pages advertising targeted to today's consumers?

PMID- 9242088
TI  - Hiring the 'write' employee.

PMID- 9242087
TI  - The boutique dental practice.
AB  - While the boutique practice enables you to have the highest quality care, highest
      levels of customer service and highest fees of any practice in dentistry, perhaps
      its greatest asset is its ability to handle changes in dentistry such as managed
      care. It's not just financially beneficial, it's also the smart way to practice
      dentistry today.

PMID- 9242089
TI  - Office of the month. Simplicity of shape and color.

PMID- 9242090
TI  - Hard tissue management?

PMID- 9242091
TI  - Periodontal repair in dogs: evaluation of rhBMP-2 carriers.
AB  - This study evaluated candidate carriers for recombinant human bone morphogenetic
      protein-2 (rhBMP-2)-driven periodontal regeneration. Previous experiments
      indicated the ability of rhBMP-2 in a particulate delivery system to result in
      substantial regeneration of bone and periodontal regeneration. In the present
      study, canine demineralized bone matrix (DBM), bovine deorganified crystalline
      bone matrix (Bio-Oss), an absorbable collagen sponge (ACS) of type I bovine
      collagen, poly(D,L-lactide-co-glycolide) microparticles (PLGA), and polylactic
      acid granules (Drilac) were tested for their ability to support rhBMP-2 (0.2
      mg/mL implant volume)-driven periodontal regeneration. The implants were tested
      in routine critical size canine supra-alveolar periodontal defects with
      transgingival tooth positioning. Contralateral defects in six beagle dogs were
      semirandomly assigned to receive: DBM/rhBMP-2, DBM (no rhBMP-2), Bio-Oss/rhBMP-2,
      ACS/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2. Animals were sacrificed 8 weeks
      postsurgery, and block sections of the defects were processed for light
      microscopy. Substantial bone regeneration was observed in all defects implanted
      with rhBMP-2. Other measures of periodontal healing, including cementum
      regeneration and presence of ankylosis, were more variable between the implants.
      DBM and Bio-Oss performed well as carriers for rhBMP-2-driven periodontal
      regeneration, although other impediments to their clinical use exist. This study
      indicates that qualities of the carrier system, including its space-maintaining
      capacity can affect the ability of rhBMP-2 to regenerate both alveolar bone and
      periodontal attachment.

PMID- 9242092
TI  - A clinical/statistical comparison between the subpedicle connective tissue graft
      method and the guided tissue regeneration technique in root coverage.
AB  - Subepithelial connective tissue grafts and guided tissue regeneration have been
      shown to be effective means to obtain root coverage. The purpose of this study is
      to compare statistically the results obtained with these techniques 1 year after
      the surgical procedures were performed. Thirty-six gingival recessions belonging
      to Class I and Class II of the Miller classification were treated: 18 cases with
      subepithelial connective tissue grafts (SCTG) and 18 cases with guided tissue
      regeneration (GTR). Each patient was randomly assigned to a group. At baseline,
      the group treated with subepithelial connective tissue grafts presented a mean
      recession of 4.88 mm, whereas the group treated with guided tissue regeneration
      presented a mean recession of 5.88 mm (P = .082). After 1 year, the mean root
      coverage was 77.08% in the SCTG group and 80.88% in the GTR group. The difference
      was not statistically significant (P > .05). The mean root coverage was 3.83 mm
      for the SCTG group and 4.61 mm for the GTR group. The mean gain in probing
      attachment level was 3.05 mm for the SCTG group and 5.55 mm for the GTR group.
      The difference was statistically significant (P = .01). In conclusion, the mean
      root coverage obtained was similar for the two groups, whereas the clinical
      attachment gain was greater in the GTR group. Therefore, it appears that the GTR
      technique is preferable when severe mucogingival defects are present and gain of
      clinical attachment level is mandatory.

PMID- 9242093
TI  - The modified papilla preservation technique with bioresorbable barrier membranes
      in the treatment of intrabony defects. Case reports.
AB  - A new surgical approach for interproximal regenerative procedures has been
      utilized in conjunction with bioresorbable barrier membranes in the treatment of
      deep intrabony defects. The purpose of this study was to test the effectiveness
      of the modified papilla preservation technique in obtaining and maintaining
      primary closure of the interdental space over bioresorbable membranes. Ten
      patients (10 sites) with optimal plaque control were treated according to the
      modified papilla preservation technique. Baseline probing attachment level and
      probing pocket depth were 10.1 +/- 1.9 mm and 8.9 +/- 2.4 mm, respectively. The
      intrabony component of the defects was 6.5 +/- 1.7 mm. Polylactic acid barrier
      membranes were positioned just coronal to the interproximal bone crest. Primary
      closure over the membranes was obtained in 100% of the cases. In two cases only a
      slight dehiscence of the interproximal tissues was observed after 2 weeks.
      Healing was uneventful in all the treated sites. Probing attachment level gains
      of 4.5 +/- 0.9 mm and a probing pocket depth reduction of 5.8 +/- 2.3 mm were
      observed at 1 year. It can be concluded that the modified papilla preservation
      technique is a suitable alternative for interproximal regenerative procedures in
      conjunction with bioresorbable barrier membranes.

PMID- 9242094
TI  - The diagnostic template: a key element to the comprehensive esthetic treatment
      concept.
AB  - Provisional restorations represent a key element in the realization of extensive
      esthetic rehabilitations. In particular, they provide indispensible diagnostic
      information contribute significantly to adjacent soft tissue conditioning, and
      ensure the patient's comfort during the intermediate phase of treatment. The
      treatment outcome strongly depends on the treatment approach chosen. This article
      describes a treatment rationale comprising the use of a diagnostic template. This
      type of work strategy, documented with clinical cases, integrates diagnostic
      waxups and indirect provisional restorations using simplified and efficient
      fabrication techniques.

PMID- 9242095
TI  - Soft tissue augmentation on previously restored root surfaces.
AB  - Three cases are presented demonstrating that soft tissue augmentation procedures
      can be accomplished on previously restored root surfaces. Diagnostic techniques
      to help determine ideal tooth length are discussed, and clinical examples of how
      to surgically manage the previously restored root surfaces are presented.

PMID- 9242096
TI  - Effect of flap design on healing and osseointegration of dental implants.
AB  - The purpose of this study was to evaluate soft tissue healing and
      osseointegration of dental implants after the use of vestibular incision or
      crestal incision flap designs during placement of the dental implant fixture. A
      split-mouth design was used in 10 patients. The vestibular flap technique was
      used for half the implant fixtures and the crestal incision for the other half.
      Postsurgical healing was monitored for 30 days, and osseointegration at second
      stage surgery was evaluated. The short-term results suggest that the use of
      either the vestibular incision or the crestal incision technique did not affect
      overall clinical healing or osseointegration.

PMID- 9242097
TI  - Resin-ionomer and hybrid-ionomer cements: Part I. Comparison of three materials
      for the treatment of subgingival root lesions.
AB  - The purpose of this study was to compare the characteristics of three different
      restorative materials for the treatment of subgingival root lesions. Eighteen
      recently extracted teeth were used to test the depth of cure and the surface
      characteristics of these products. Although none of the materials tested
      exhibited all of the author's ideal characteristics for a subgingival
      restoration, one restorative material displayed the most favorable result.

PMID- 9242098
TI  - The knowledge game.

PMID- 9242099
TI  - Soft tissue ridge augmentation utilizing a combination onlay-interpositional
      graft procedure: a case report.
AB  - Esthetic reconstruction of large-volume Class III ridge deformities where bone
      and soft tissue have been lost buccolingually as well as apicocoronally continues
      to offer a major challenge in therapy to periodontists and to those engaged in
      advanced reconstructive dentistry. No single procedure is well suited for solving
      all problems in reconstructive surgery. A series of staged surgical procedures is
      frequently necessary to augment the ridge to its former dimensions. The authors
      have devised a combination onlay-interpositional graft procedure that appears to
      offer promise in solving many of the problems encountered in gaining predictable
      soft tissue ridge augmentation in Class III ridge defects.

PMID- 9242100
TI  - Influence of residual ridge resorption patterns on fixture placement and tooth
      position, Part III: Presurgical assessment of ridge augmentation requirements.
AB  - Implant diagnostic methods using computed tomography with barium-coated templates
      have revealed the relationship between the optimal final tooth position and the
      residual alveolar process or ridge. While information with regard to emergence
      axis, anatomic limitations, fixture length, buccolingual cantilever, and
      prediction of the the final prosthetic design is available, presurgical
      information relating to the reconstruction potential of smile zone deformities
      remains elusive. The use of a complete provisional wax-up and the modification of
      a barium-coated template design can provide the implant team with presurgical
      information regarding the need for augmentation of hard tissue and soft tissue
      and the volume of tissue needed for reconstruction. This information can assist
      the implant team in the development of realistic treatment objectives and in more
      accurately addressing the needs and concerns of the patient during presurgical
      treatment planning.

PMID- 9242101
TI  - GBR with an e-PTFE membrane associated with DFDBA: histologic and histochemical
      analysis in a human implant retrieved after 4 years of loading.
AB  - As a result of a fracture to the cemented post and core, a pure titanium implant
      was extracted from a 54-year-old patient after 4 years of clinical loading. At
      implantation, the implant was positioned into an extraction socket and the defect
      was treated with an e-PTFE membrane associated with a DFDBA graft. At retrieval
      the implant underwent histologic and histochemical examination to assess the
      characteristics of the regenerated bone after 4 years of prosthetic loading. The
      implant showed an angular bony defect at the smooth collar, but the bone-implant
      direct contact rate seemed to be elevated in the remaining implant surface.
      Normal transmitted and polarized light examinations demonstrated that most of the
      DFDBA particles were resorbed and substituted by vital newly formed bone. The
      regenerated bone appeared compact with secondary osteons and large haversian
      canals; however, some partially mineralized remnants residuated in the spaces,
      between the osteons. Within the limits of this study, the authors concluded that
      DFDBA can be substituted by the host bone, but the rate of substitution is very
      slow and not complete after 4 years. From a clinical point of view, however, the
      load-bearing capacity of the bone regenerated with the membrane technique
      associated with DFDBA appeared to be similar to that of normal bone.

PMID- 9242102
TI  - Connective tissue grafting for primary closure of extraction sockets treated with
      an osteopromotive membrane technique: surgical technique and clinical results.
AB  - This article describes a grafting technique using connective tissue to
      predictably obtain primary closure of extraction sockets treated with an
      osteopromotive membrane technique. This technique was used for a total of 24
      sites in 22 consecutive patients to regenerate alveolar bone in severely damaged
      ridges and in conjunction with implants immediately installed into extraction
      sites. Two sites (8.3%) were complicated by premature membrane exposure that
      necessitated early removal. In the remaining 22 sites, membranes remained
      completely covered for a mean period of 23.75 weeks (SD = 8.21 weeks; range = 10
      to 38 weeks).

PMID- 9242103
TI  - Treatment of buccal gingival recessions with e-PTFE membranes and miniscrews:
      surgical procedure and results of 12 cases.
AB  - A surgical technique to achieve root coverage in buccal gingival recessions by
      means of expanded polytetrafluoroethylene membranes in combination with
      miniscrews is presented. After raising a trapezoidal split flap, supporting
      screws were used to create a large space underneath the membrane, while head
      screws were employed for perfect stabilization of the Teflon barrier. Intramarrow
      perforations were made to induce the rapid formation of a large blood clot with
      abundant availability of progenitor cells. The membrane and the miniscrews were
      removed after 3 or 4 weeks. The treatment of 12 cases, with mucogingival defects
      4 to 7 mm deep, resulted in a mean root coverage of 84%.

PMID- 9242104
TI  - Treatment planning: teeth versus implants.
AB  - Attempts to save natural teeth have created numerous restorative, endodontic, and
      periodontal techniques it has always been considered the treatment of choice to
      save teeth whenever possible, and extreme efforts to save teeth are often
      considered because of the poor treatment alternatives for replacing them. Today
      osseointegration provides a predictable means of replacing teeth; therefore,
      retaining questionable teeth may not be as necessary as in the past. This article
      reviews situations in which the selective extraction of compromised natural teeth
      or even healthy natural teeth is considered because of alternative treatment
      options utilizing osseointegrated implants.

PMID- 9242105
TI  - Guided tissue regeneration of deep intrabony defects in strategically important
      prosthetic abutments.
AB  - This study reports the clinical outcomes obtained in a longitudinal cohort of 23
      patients treated by guided tissue regeneration for strategically important teeth
      compromised by the presence of deep intrabony defects. After completion of
      initial periodontal therapy and placement of a provisional fixed partial denture,
      a nonresorbable e-PTFE membrane was applied to isolate the defect. Changes in
      probing attachment level, probing pocket depths, and radiographic bone support
      were evaluated 12 months after removal of the membrane. Clinically and
      statistically significant improvements in outcome measurements were observed: a
      probing attachment level gain of 5.3 +/- 1.7 mm, a reduction in probing pocket
      depths of 6.1 +/- 2 mm, and an increase in the percentage of radiographic bone
      support of 31% +/- 18%. The results obtained were highly reproducible with 91.3%
      of the cases resulting in probing attachment level gains of 4 mm or more. The
      evidence provided in this investigation indicates that guided tissue regeneration
      can predictably increase the functional support, and possibly improve the
      prognosis of strategically important abutments. Guided tissue regeneration
      therapy should, therefore, be one of the options discussed in treatment planning
      for complex periodontal-prosthetic cases.

PMID- 9242106
TI  - A comparison of papillary retention versus full-thickness flaps with internal
      mattress sutures in anterior periodontal surgery.
AB  - Esthetic considerations pose therapeutic dilemmas in the selection of surgical
      techniques in anterior periodontal surgery. Two surgical techniques designed to
      maximize postoperative esthetics in the anterior regions are described. Changes
      in interdental papillary height are reported and compared at 1 year
      postoperative. This study discusses the surgical techniques, their advantages and
      disadvantages, and their indications. Since there is less risk of recession and
      more potential for gain in papillary height, the papillary retention procedure,
      when possible, may be the procedure of choice in anterior regions.

PMID- 9242107
TI  - The extraoral extraction of teeth--report of a case.

PMID- 9242108
TI  - Aetiology and treatment of anterior open bite.
AB  - AOB can be acquired or skeletal in nature. Treatment of skeletal open bites can
      be difficult, especially with fixed appliances. Magnetic biteblocks have recently
      gained popularity. Surgery may be necessary in the patient with a severe skeletal
      discrepancies and usually involves differential maxillary impaction.

PMID- 9242109
TI  - Patterns of attendance and treatment at an emergency dental clinic.

PMID- 9242110
TI  - Yes, giants, neither diseased nor apes.

PMID- 9242111
TI  - Sub-standard dental X-ray units.
AB  - In summary the Institute hopes that implementing the provisions of the new Code
      of Practice will result in a reduction in doses to patients and an improvement in
      image quality. Further information regarding the licensing of dental X-ray units
      may be obtained from the Regulatory Service of the Radiological Protection
      Institute of Ireland, tel. 01-2697766.

PMID- 9242112
TI  - Anti-plaque mouthwashes: I--Efficacy and modes of action.

PMID- 9242113
TI  - Anti-plaque mouthwashes: II--Side effects and potential health hazards.

PMID- 9242114
TI  - Oral surgery at St. Mary's Hospital, Chapelizod. A quarter century experience of
      day-case oral surgery.
AB  - To mark the first quarter century of the existence of the Oral Surgery unit at
      St. Mary's Hospital, Chapelizod, an audit was undertaken. Twenty-nine thousand,
      three hundred and seventy-four (29,374) entries in the operations register were
      analysed, examining annual totals, categories of operation, the changing patterns
      of anaesthesia, including cancellations on the day, and the evolution of a true
      day-case service. The results showed a decline in total numbers and in some
      operation categories. The most striking reductions were in extractions of carious
      teeth and in preprosthetic surgery. The most marked increase was in surgery for
      impacted teeth. While general anaesthesia remains the most commonly used form of
      anaesthesia, there has been an increased utilisation of sedation. Since the
      earlier years the number of patients requiring admission post-operatively has
      steadily decreased but more patients have been cancelled on the day of operation.
      Most of the changes described reflect the influence of health care economics and
      the effects of fluoridation.

PMID- 9242115
TI  - The Kenyan experience.

PMID- 9242116
TI  - Lessons learnt from the amalgam controversy.

PMID- 9242117
TI  - Modified bovine type I collagen membrane as a wound graft material in oral
      surgery (an experimental study).
AB  - The use of collagen biomaterials in various types, structures and forms to aid in
      wound healing and in reconstructive surgery has been reported in several
      occasions in the literature. This paper evaluates the biocompatibility and
      effectiveness of a modified bovine type I collagen membrane as a graft material
      in experimental oral wounds in dogs. 2.5 x 2.5 cm wounds were prepared
      bilaterally in the labial mucosa of nine dogs. Bovine type I atelopeptide
      reconstituted collagen membrane was placed over the surgery site on one side of
      the labial mucosa. The contralateral sides served as controls. Clinical and
      histopathologic evaluation were done at 1, 2 and 3 weeks post-operatively,
      comparing the experimental side with the control side. Results demonstrated an
      improved rate of wound healing on the experimental side. The collagen membrane
      had a topical hemostatic effect at the time of its application and did not cause
      any adverse reaction post-operatively. It is concluded that the modified collagen
      membrane used in this study is biologically acceptable to the oral mucosa and is,
      from the clinical point of view, an excellent wound graft material. The clinical
      utilization of these collagen sheets offers exciting applications in the field of
      oral surgery.

PMID- 9242118
TI  - An unusual dilacerated root of a second maxillary molar.
AB  - An unusual case of a second maxillary molar with a dilacerated root visible
      clinically is described. Apicectomy followed by retrograde amalgam filling was
      performed whereby gingival coverage and gingival seal was achieved.

PMID- 9242119
TI  - Regional orthodontics: Class II division I malocclusion, a variety of orthodontic
      treatments.

PMID- 9242120
TI  - Professional bleaching of teeth in dental practice techniques.

PMID- 9242121
TI  - The staff is the judge and the jury.

PMID- 9242122
TI  - Papillary (pebbled) masses of the oral mucosa: more than simple papillomas.
AB  - Soft tissue masses are found in almost 4% of adult dental patients, and most of
      these will never be biopsied. Clinical evaluation, therefore, is of paramount
      importance. Oral mucosal masses with irregular or nodular surface alterations are
      of special concern. These alterations may appear to be papillomas, but there are
      several type of papillomas, and among the lesions which present with a papilloma
      like appearance are diverse malignancies, contagious infections, sexually
      transmitted diseases, vascular and reparative lesions, and viral proliferations
      associated with a wide range of different types of human papillomavirus. The
      learning objective of this article is to present a clear, clinically oriented
      approach to the diagnosis and management of pebbled and lobulated intraoral
      masses, enabling the clinician to provide a more meaningful clinical diagnosis
      and prognosis. For the differential diagnosis discussion, the authors have
      selected only those entities with the preliminary diagnosis of "papilloma."

PMID- 9242123
TI  - Giant cell tumor in the mandible: surgical treatment and implant-supported
      reconstruction--a clinical report.
AB  - Giant cell tumors of the jaw are extremely rare. The malignant variants of these
      tumors are distinguished by their rapid growth, pain, or tumor paraesthesia. The
      lesions generally manifest as multilocular radiolucencies of bone with well
      differentiated margins. If not diagnosed and treated, the lesions may resorb the
      alveolar ridge and displace the roots of the teeth. The learning objective of
      this article is to present the diagnosis of the lesion, mandibular resection,
      bone graft augmentation of the surgical site, implant placement, and restoration
      of oral function by implant-supported prosthesis. Multidisciplinary approach and
      cooperation are credited for the successful final result.

PMID- 9242124
TI  - Treatment of chronic periodontitis: a site-specific fiber placement technique.
AB  - Bacterial flora has resisted the conventional treatment in a segment of patients
      with adult periodontitis, creating an interest in adjunctive chemotherapeutic
      treatment modalities. Tetracycline hydrochloride periodontal fiber, a locally
      delivered antibiotic therapy, is indicated as an adjunct to scaling and root
      planing. This form of treatment has demonstrated a reduction in bleeding on
      probing and periodontal pocket depths. Clinicians have found the fiber placement
      technique challenging, and a considerable percentage of fibers become dislodged
      during the course of the 10-day treatment period. This article clarifies the
      treatment protocol and presents an alternative placement technique for
      tetracycline fiber. It simplifies the procedure for the clinician and aids in
      fiber retention. The learning objective of this article is to familiarize the
      reader with the technique and the materials utilized for site-specific
      tetracycline hydrochloride fiber therapy. A clinical case is used to illustrate
      the procedure.

PMID- 9242126
TI  - Occipital neuralgia: symptoms, diagnosis, and treatment.

PMID- 9242125
TI  - Clinical management of infected root canal dentin.
AB  - Several hundred different species of bacteria are present in the human intraoral
      environment. Bacterial penetration of root canal dentin occurs when bacteria
      invade the root canal system. These bacteria may constitute a reservoir from
      which root canal reinfection may occur during or after endodontic treatment. The
      learning objective of this article is to review endodontic microbiology, update
      readers on the role of bacteria in pulp and periapical disease, and discuss the
      principles of management of infected root canal dentin. Complete debridement,
      removal of microorganisms and affected dentin, and chemomechanical cleansing of
      the root canal are suggested as being the cornerstones of successful endodontic
      therapy, followed by intracanal medication to remove residual bacteria, when
      required.

PMID- 9242127
TI  - Conservative restoration of function and aesthetics in a bulimic patient: a case
      report.
AB  - Traditionally, the treatment of acid erosion lesions of the maxillary and
      mandibular dentition has been invasive, often utilizing full-coverage crown
      restorations. Intentional endodontic and post-and-core treatments have been used
      in the past to gain crown length for retention of cemented cast restorations. The
      learning objective of this article is to discuss the primary cause of acid
      erosion-bulimia nervosa-and present an alternative dental treatment modality. The
      alternative treatment uses conservative tooth preparation, dentin bonding
      technology, and pressed ceramic restorations, achieving aesthetic results. The
      indications and advantages are discussed, and a case report illustrates the
      clinical procedure. The importance of achieving the cessation of the purging
      habit as a prerequisite to dental treatment is emphasized.

PMID- 9242128
TI  - Aesthetic all-ceramic restorations: a philosophic and clinical review.
AB  - The current focus of aesthetic dentistry is on tooth-colored, metal-free
      restorations in the anterior and the posterior regions and the biocompatibility
      and toxicologic safety of these restorative materials. This article reviews eight
      years of clinical experience with all-porcelain restorations and documents the
      observations of several clinical cases. It discuss tooth preparation for all
      ceramic inlays, onlays, and veneer and crown restorations, as well as isolation,
      etching, placement, bonding, and lightor dual-curing of the materials. The
      learning objective of this article is to share the experience and observations
      with other clinicians. The author concludes that restorations, identical to
      natural dentition, can be predictably achieved with current allporcelain systems
      and that critical scientific analysis of dentin bonding agents must continue. The
      utilization of all-porcelain material in multiple-unit bridges should still be
      viewed with caution, and further long-term experience is required.

PMID- 9242130
TI  - White teeth won't go away, will they?

PMID- 9242129
TI  - Ernest syndrome: insertion tendinosis of the stylomandibular ligament.

PMID- 9242131
TI  - Posterior composite resin restorations: operative innovations.
AB  - The adhesive revolution is alleviating reservations regarding posterior composite
      resin restorations, established by past experience with outdated materials and
      techniques. Improved materials, instrumentation, and placement techniques have
      enhanced the performance of current formulations of posterior composite resins
      over their predecessors. However, it is a clinician's operative skill that
      ultimately determines the quality of a restorative option. The learning objective
      of this article is to share the author's experience in attaining adhesive
      excellence with posterior tooth-colored restorations as well as aesthetic
      anatomic form, minimal postoperative sensitivity, and a bond which can weather
      the true test of success-durability. Optimal applications, dental dam
      requirement, importance of the first increment of composite resin, restitution of
      occlusal morphology, and the clinical application are discussed.

PMID- 9242132
TI  - C. Edmund Kells lives on.

PMID- 9242133
TI  - A dentigerous cyst of the maxilla presenting as a periodontal lesion: a case
      report.

PMID- 9242134
TI  - The function of mastication: a key determinant of dental occlusion.
AB  - To explain the static and dynamic relationship between the dental arches, models
      of functions, based on the observation of protrusion and lateral movements of the
      mandible, are generally presented. In clinical practice, the patients are
      frequently asked to complete such artificial test movements in order to assess
      occlusion. However, these movements are in contradiction with the knowledge
      acquired through examination of the kinetics of incision, mastication, and the
      posterior dental contacts. The learning objective of this article is to present
      the required integration of physiology and the kinetics of mastication with any
      occlusodontic procedure. Interpretation of muscular action during mastication,
      incision, trituration, and intradental functional guidance are discussed and
      illustrated.

PMID- 9242135
TI  - Composite resins: the transition from traditional to modern dentistry.

PMID- 9242136
TI  - Current developments in composite materials and techniques.
AB  - General reduction of dental caries and patient interest in dental aesthetics have
      resulted in the development of new restorative materials and techniques.
      Composite materials and adhesive techniques have become the foundation of modern
      restorative dentistry. Mechanical performance, wear resistance, and aesthetic
      potential of composite resins have been significantly improved, and the material
      is now used in cases ranging from the restoration of initial decays and cosmetic
      corrections to the veneering in extended prosthetic rehabilitation.
      Polymerization shrinkage of the resin matrix remains a challenge and still
      imposes limitations in the application of direct techniques. The learning
      objective of this article is to review the most significant advances of composite
      materials and the importance of utilizing the available treatment options with
      discretion, selecting those which preserve the tooth structure and require the
      least maintenance.

PMID- 9242137
TI  - The direct/indirect composite resin veneers: a case report.
AB  - Veneer restorations are well suited for conservative and aesthetic improvement of
      the anterior dentition. Laboratory fabricated porcelain and composite resin
      veneers present optimal aesthetics and durability. Although there are
      disadvantages associated with direct bonding, it provides control of color and
      contour for the operator, particularly in the case of a single anterior central
      incisor. Direct/indirect composite resin veneers utilize the advantages of both
      direct and indirect techniques in reconstruction of restorations with improved
      physical properties. The learning objective of this article is to review the
      available composite resins, opaquers, and tints, and present a step-by-step
      protocol for predictable restoration of discolored anterior dentition with
      direct/indirect heat-treated composite resin veneers in a single appointment.
      Patient evaluation, preoperative aesthetic considerations, selection of the
      restorative composite resins, and the clinical procedure are discussed.

PMID- 9242138
TI  - Diagnostic use of composite in anterior aesthetics.
AB  - The success of anterior restorative procedures is in direct proportion to the
      ability of the practitioner to master new techniques and materials, which
      constantly improves the level of aesthetics and ultimately the final results
      achieved. However, unless a harmonious integration is achieved involving the two
      "bioaesthetic" parameters-the gingival architectural design and the dental
      architectural design-the final result will not be satisfactory. The learning
      objective of this article is to illustrate the use of composite resin as an
      "architect" to build predictable and successful anterior restorations through
      more reliable diagnostics of natural aesthetics and function. Freedom of
      composite build-up is outlined, and the use of composite in moving and opening of
      the gingival crest is described. Direct and indirect diagnostic use of composite
      in dental procedures is outlined in a detailed clinical procedure.

PMID- 9242139
TI  - The evolution of aesthetic restorative materials for inlays and onlays: a review.
AB  - Composite and ceramic restorations are well-accepted treatment modalities for
      anterior as well as posterior regions, and numerous systems are available. This
      article presents the historical development of tooth-colored restorations from
      their incipience in 1882 to the second generation laboratory composites of today.
      The causes of failures in the early ceramics are discussed, and the search to
      delineate the optimal qualities of ceramics is outlined, listing the improvements
      of each new generation. The inherent obstacle of ceramic brittleness is reviewed
      along with the specific requirements of preparation. The learning objective of
      this article is to present the development of tooth-colored restorations in a
      concise form and indicate the characteristics of the materials currently
      available.

PMID- 9242140
TI  - Light and color in anterior composite restorations.
AB  - As defined by physics, color is light. With this premise, this article highlights
      the importance of the interaction between light and the hard tissues of the tooth
      as compared to the interaction between light and composite restorative materials.
      Based on the philosophy of color interpretation and its subsequent practical
      application in the development of a fluorescent and opalescent microhybrid
      composite system, the protocol outlined allows the clinician to achieve
      restorations with a light/composite interaction that closely resembles that of
      light/natural dentition. The learning objective of this article is to present
      specific diagnostic techniques to establish predictable identification and
      reproduction of the natural anatomy and nuance color characteristics exhibited by
      natural dentition with composite resin. A detailed evaluation of hue, chroma,
      opalescence, and fluorescence are presented in order to simplify the composite
      stratification technique.

PMID- 9242141
TI  - Orofacial myofunctional disorders.

PMID- 9242142
TI  - Just do it!

PMID- 9242143
TI  - Direct and semi-direct posterior composite restorations.
AB  - Since the introduction of composite resins in dentistry, the adhesive properties
      of the material to enamel and dentin surfaces have been improved considerably,
      resulting in more conservative cavity preparation and the preservation of natural
      tooth structure. Patient demand for aesthetic metal-free restorations in the
      posterior region has resulted in the utilization of tooth-colored composite
      restorations. The primary disadvantage of composite resins-material shrinkage-can
      be minimized, but not eliminated. Various techniques have been developed and
      proposed in order to overcome this important limitation. The learning objective
      of this article is to provide indications for the direct and semi-direct
      techniques and to illustrate effective clinical procedures for placement of
      posterior composite resin restorations. The article outlines the treatment
      concepts, principles of cavity preparation, direct and semi-direct restorative
      methods, and the technique-sensitive luting procedures. Several cases are used to
      illustrate the clinical aspects.

PMID- 9242144
TI  - Aesthetic success or failure in implant-supported anterior restorations.

PMID- 9242145
TI  - Implant-supported single tooth replacement in the aesthetic region: a complex
      challenge.
AB  - The placement of a single tooth implant-supported restoration in the maxillary
      anterior area still presents a difficult challenge. To address this challenge,
      various methods and techniques have been proposed. The learning objective of this
      article is to present a particular clinical protocol for achieving predictable
      aesthetic restoration, even under the relatively difficult circumstances
      involving thin, highly scalloped gingiva and high lip line. A clinical case is
      used to illustrate the presentation of implant surgery, bone regeneration,
      connective tissue graft, provisionalization, and placement of the definitive
      prosthetic restorations. The use of pressure to expand soft tissue is described,
      and the importance of papillae protection is emphasized.

PMID- 9242146
TI  - Periimplant tissue management: optimal timing for an aesthetic result.
AB  - When implants are utilized to restore the dentition in an aesthetically prominent
      region, there are four different time points when the periimplant tissue can be
      influenced-prior to implant placement, simultaneously with implant placement or
      during the healing phase of the implant, at second-stage surgery, and during the
      maintenance phase. There is no single optimal point in time for managing the
      periimplant tissues; the patients present for treatment at various stages, and
      each case has to be individually evaluated and an appropriate treatment plan
      designed. The earlier periimplant tissue management is initiated, the greater are
      the opportunities for a successful result. The learning objective of this article
      is to review these options by means of case presentations. The different surgical
      procedures are explained and their advantages or disadvantages discussed. Four
      case reports are used to demonstrate the rationale and the clinical procedures.
      An improvement in the aesthetic harmony was attained in all four cases.

PMID- 9242147
TI  - Implant-supported restorations in the anterior region: prosthetic considerations.
AB  - Achieving functional and aesthetic implant-supported restorations in the
      partially edentulous patient can be particularly challenging when the implant
      sites are in the anterior region and not in harmony with the adjacent dentition.
      The learning objective of this article is to focus on presurgical evaluation of
      anterior implant sites and systematic development of related therapeutic
      modalities. Utilization of guided bone regeneration and connective tissue
      grafting predictably facilitates implant positioning that is compatible with
      required aesthetic restoration and soft tissue contours. Other aspects, such as
      abutment protection caps with variable emergence profiles, provisional
      restorations for the development of optimal periimplant soft tissue contours, and
      fabrication guidelines for different types of prosthetic restorations, are also
      discussed.

PMID- 9242148
TI  - Influence of the implant position on the aesthetics of the restoration.
AB  - Well-placed implants are a prerequisite to achieving functional as well as
      aesthetically successful implant-supported restorations. In addition to
      sufficient bone volume, a precise emergence profile is an important factor in
      obtaining the optimal result of the final restoration, presenting a natural
      gingival silhouette. Restorations with a ridge lap design are no longer
      acceptable. The learning objective of this article is to review implant placement
      with emphasis on the factors that influence implant position and angulation.
      Anatomic discrepancies between the natural tooth root and the implant are
      discussed in context of treatment planning, including the position and direction
      of the implants, determined by the anticipated prosthetic restorations. The
      sagittal plane of implant position is reviewed versus horizontal or vertical
      placement in the anterior as well as posterior region. Function, comfort, access
      for hygiene, and aesthetics are the four essential requirements for an implant
      supported restoration.

PMID- 9242150
TI  - Who can you believe?

PMID- 9242149
TI  - Dental implants for children: creating smiles for children without teeth.

PMID- 9242151
TI  - NICO. Necrotizing ischemic chronic osteitis.

PMID- 9242152
TI  - The orthodontic-periodontal connection in implant site development.
AB  - Implant-supported restorations have become an established treatment modality,
      well accepted by patients and clinicians. Regaining function is now routinely
      expected, and the focus of patient demand has shifted to aesthetics. Aesthetic
      restoration of the partially edentulous anterior maxilla can be particularly
      challenging. The learning objective of this article is to present a comprehensive
      multidisciplinary treatment protocol, developed to establish a foundation for
      optimal aesthetics in implant therapy, with emphasis on the role of orthodontics
      in the enhancement of deficient components. Periodontal orthodontics is used to
      increase the vertical osseous dimension and preserve papillae; restorative
      orthodontics optimizes the site through manipulation of supragingival restorative
      space. Two clinical cases are utilized to illustrate the principles and
      implementation of this protocol.

PMID- 9242153
TI  - Venous disease: from pathophysiology to quality of life.
AB  - Venous insufficiency is a multifactorial pathology that has an important impact
      on the quality of life of the patients. The primary factor of venous disease is
      an abnormal wall distensibility, which seems to be correlated with genetic
      factors. Facilitating factors include hormonal impregnation and prolonged
      hydrostatic load, particularly under conditions where the control of the
      sympathetic nervous system is reduced by an increase in local temperature. The
      resulting valvular incompetence, combined with the augmented hydrostatic load,
      leads to varicosis and venous stasis. The ensuing tissue hypoxia and local edema
      favor inflammation and infection, which ultimately favor the occurrence of
      ulcers. The available data on the impact of the disease suggest a relation
      between the physiopathological phenomena and some parameters of health-related
      quality of life.

PMID- 9242154
TI  - Epidemiology of chronic venous insufficiency.
AB  - In contrast to the knowledge on the frequency and determinants of arterial
      diseases, little epidemiologic research has been carried out on venous diseases;
      this may be partly due to methodological problems in defining chronic venous
      insufficiency and in measuring these conditions with sufficient validity.
      Epidemiologic studies that were published after 1965 and that are not based on
      clinical series are reviewed; prevalence and incidence rates are reported.
      Studies of risk factors for varicose veins have largely resulted in inconsistent
      results; the sex difference is universal while the large geographical differences
      suggest strong environmental influences. For all other determinants much of the
      variation between studies is probably related to differences in definition, in
      population-sampling techniques, and in assessment methods. Several plausible
      etiologic theories on the causes and development of chronic venous insufficiency
      are supported or refuted by the epidemiologic studies. Further research is
      needed, whenever possible cross-cultural, with particular emphasis on clear
      definitions, valid methods, and a prospective study design.

PMID- 9242155
TI  - Venous insufficiency at work.
AB  - Chronic venous disease of the lower limbs is one of the most common conditions
      affecting humankind. It has been postulated that certain workplace conditions may
      be risk factors for venous insufficiency and varicose veins in particular. This
      paper examines the evidence for a link between occupation and the prevalence of
      venous disease. It also reviews recent French research carried out to estimate
      the prevalence of chronic venous insufficiency in a working population; work and
      nonwork risk factor and the cost to industry from this condition are also
      examined.

PMID- 9242156
TI  - Epidemiology and costs of venous diseases in central Italy. The San Valentino
      Venous Disease Project.
AB  - The Prevalence of Early Atherosclerosis study aims to define the prevalence of
      subclinical atherosclerosis in a typical population of central Italy. A
      concomitant study evaluates the prevalence of venous diseases. The prevalence of
      superficial and deep venous disease, the prevalence of venous thrombosis and
      pulmonary embolism, and the prevalence of the most common venous malformations
      were studied through use of medical history, a questionnaire, and noninvasive
      investigations. The costs of venous problems were also considered. Of some 2000
      inhabitants, 746 (379 women; mean age 46.3 +/- 7 years; range eight to ninety
      four) have been screened. No significant difference in trend increase of the
      relationship age/percent of subjects with venous problems was observed for
      superficial venous disease. The increase in the proportion of subjects with
      lipodermatosclerosis and venous ulcerations appeared to be correlated with age (r
      = 0.543). Evidence accepted for pulmonary embolisms was pulmonary angiogram or
      evidence on ventilation+perfusion lung scans. According to these criteria the
      number of documented deep vein thromboses and pulmonary embolisms was very
      limited with a larger number of suspected disease entities. There was no
      significant correlation between age and pulmonary embolism or deep venous
      thrombosis distribution. The number of venous and/or arteriovenous malformations
      was comparable along the age axis in the different age groups. Only a limited
      number of these malformations (in less that 1% of subjects) had caused a clinical
      problem. The treatments used for venous problems have been reported in a
      questionnaire and subdivided into occasional treatments and chronic treatments
      (when used for periods longer than twelve months). The percent of subjects using
      different treatment was also studied. Treatments were divided in: (1) over-the
      counter products (or any treatment not requiring prescription); (2) specialized
      drug (for venous diseases); (3) compression; (4) surgery (any type of surgical
      treatment); (5) sclerotherapy; (6) combined treatments (ie, sclerotherapy and
      surgery); (7) alternative treatments (herbal products etc). Finally, the average
      costs per year for treatment, for investigations, and the costs due to lost
      working days were recorded. In conclusion some 12% of the evaluated population
      sample (male population 46%) had or had been affected in the past by a venous
      problem and 50% of them had received some type of treatment.

PMID- 9242157
TI  - The socioeconomic profile of patients treated by phlebotropic drugs in Germany.
AB  - Conservative treatment of venous disease is difficult. There is much skepticism
      concerning the efficacy of drugs in venous diseases. Nevertheless, in Germany,
      these drugs have obtained a substantial market share with a tendency to increase.
      The objective of this empirical study is to evaluate the socioeconomic
      characteristics of consumers of venous medications and to explore the demand
      elasticity with respect to health insurance coverage. In a first set of inquiries
      12,500 households were asked from July to September 1993 if they had purchased
      prescribed venous medication during the past 12 months. About 10,000 households
      with 19,750 persons aged fifteen years and older responded; 2,080 (11%) of those
      persons had consumed prescribed medications against venous disease over the past
      twelve months. In the second part of the study a detailed questionnaire was sent
      to the 2,080 purchasers and to 3,000 randomly selected nonpurchasers; 1,930
      (92.8%) purchasers and 2,291 (76.4%) nonpurchasers returned their questionnaire.
      The key findings can be summarized as follows: The percentage of women is much
      higher in the group of purchasers (80%) than in the group of nonpurchasers. Most
      of the purchasers are over fifty years old. Only one quarter of the purchasers
      are under fifty. One third of the purchasers are retired, and only 29% are
      working. In the group of nonpurchasers 56% are working and only 17% are retired.
      A comparison of the distribution of purchasers and nonpurchasers over income
      classes and education levels shows that higher income and higher education are
      less prevalent in the group of consumers of venous medications. Varicose veins
      (58%) and various leg complications (30%) and pain in the legs (30%) play a
      dominant role for applying venous medications. The analysis shows that pregnancy
      and chronic diseases are risk factors for venous disease and are more prevalent
      in the purchasers group. We did not, however, discover a significant difference
      in the share of smokers, and it is quite low in the group of purchasers (14%).
      Only 45% of the purchasers feel that their venous disease has a negative
      influence on their spare-time activities, their family life, or their work.
      Purchasers consult a physician on the average 3.7 times a year; 40% of the
      managers, merchants, and self-employed craftsmen have no physician consultation
      at all. Owing to the pain and trouble of some complications of venous disease,
      only a relatively low percentage of purchasers would react to a reduction of
      health insurance coverage of venous medications; 5% would stop buying these drugs
      and 22% would reduce consumption if they would have to pay the cost out-of
      pocket.

PMID- 9242158
TI  - Incidence of atheroembolic renal failure after coronary angiography. A
      prospective study.
AB  - Atheroembolic renal failure (AERF) is often seen after vascular procedures in
      elderly atherosclerotic patients. To estimate the incidence of AERF after
      coronary angiography, all patients undergoing coronary angiography at the V.A.
      Medical Center, Dayton, were prospectively evaluated for AERF. Since, unlike
      contrast nephropathy, AERF develops about a week after the vascular procedure and
      persists or progresses over weeks and months, serum creatinine was measured just
      prior to and 3 weeks after coronary angiography. Peripheral signs of cholesterol
      emboli were also looked for at follow-up visits. Two hundred sixty-seven patients
      underwent coronary angiography over a fifteen-month period. Most of the patients
      were sixty years old or older. Mean serum creatinine in these patients prior to
      coronary angiography was 1.2 mg/dL. Mean serum creatinine after coronary
      angiography was unchanged (1.2 mg/dL). Only 7 patients had serum creatinine > 2
      mg/dL prior to coronary angiography. Two patients died within a week of coronary
      angiography and 2 did not return for follow-up. Of the remaining 263 patients, 5
      had a serum creatinine increase by 0.5 mg/dL or more at three weeks after
      coronary angiography. Three of 5 had a serum creatinine increase by 1.0 mg/dL or
      more. Two of these 3 patients eventually died of renal failure. None of these 5
      patients had peripheral signs of cholesterol emboli. In selected patients, the
      incidence of AERF after coronary angiography appears to be very low (< 2%).

PMID- 9242159
TI  - Noninvasive detection of iliac artery disease and prediction of its severity from
      Doppler spectral analysis in common femoral artery.
AB  - The direct interrogation of iliac artery disease (IAD) with color-coded duplex
      scanning is limited by the presence of intestinal gas or obesity. The purposes of
      this study were to examine the diagnostic accuracy of duplex ultrasound (DUS)
      analysis of spectral waves in common femoral artery (CFA) for detection of IAD
      and to predict its severity. DUS and arteriography were performed in 107 lower
      extremities in this study. The following were calculated from the CFA spectral
      waves obtained by DUS: peak systolic velocity (PSV), acceleration (PSV/pulse rise
      time), and deceleration (PSV/pulse decay time). In patients with isolated IAD,
      the treadmill exercise test was also performed to evaluate the ischemic severity
      expressed as recovery rate of ankle pressure index five minutes after exercise
      (RR-API). Forty-six lower extremities with IAD and 61 without IAD were diagnosed
      by arteriography. PSV was significantly reduced in lower extremities with IAD
      (109.5 +/- 32.7 vs 59.8 +/- 32.9 cm/s, P < 0.05). The deceleration detected IAD
      with a greater specificity and sensitivity vs acceleration (100.0 vs 82.0% and
      97.8 vs 82.6%, respectively). Moreover, the acceleration and deceleration
      significantly correlated with the RR-API (r = 0.589, P < 0.05 and r = 0.779, P <
      0.01, n = 14, respectively). The present evaluation is a simple and accurate
      technique to augment other examinations for detection of IAD and to assess its
      ischemic severity.

PMID- 9242160
TI  - Atherosclerosis vascular damage in elderly athletes and sedentary people.
AB  - The objective of this study was to determine the degree of vascular
      atherosclerotic damage at the carotid and femoral levels in a group of subjects
      over sixty years old practicing endurance sports. Using high-resolution Doppler
      color flow ultrasonography the authors carried out a vascular screening,
      comparing two distinct groups of subjects, the first consisting of 20 elderly
      male subjects (age 65.6 +/- 5.6 years) practicing endurance sports (runners) and
      the second of 20 subjects of the same gender and age (63.5 +/- 4.5 years),
      clinically healthy, but leading a sedentary life. All subjects were nonsmokers,
      nondiabetics, with normal lipid values and normal blood pressure. The authors
      examined the internal, external, and common carotid arteries, bilaterally, as
      well as the common femoral, deep femoral, and superficial femoral arteries of
      both legs. For each vessel they documented: (1) presence of plaques, (2) position
      and quantity of the plaques, (3) stenosis percentage produced by the plaques, (4)
      echographic structure of the plaques. In the group of sportsmen they calculated a
      global score of atherosclerotic damage of 5.58 +/- 2.21. This is statistically
      significant (P < 0.001) as compared with the global score observed in the
      sedentary group (9.24 +/- 3.9, range 6-14). The sportsmen exhibited small
      atherosclerotic plaques that were not hemodynamically significant; these plaques
      were present in 7 subjects (35%). In 4 of them (20%) the lesions were located in
      one carotid artery system. In the other 3 subjects (15%) the lesions were
      identified in one femoral artery system. In none of the sportsmen were they able
      to demonstrate simultaneous atherosclerosis of carotid and femoral arteries. In
      the sedentary subjects, atherosclerotic lesions were identified in 15 of them
      (75%). In 2 subjects hemodynamically significant plaques were located in one
      carotid artery system. In the other 13 subjects the plaques found were not
      hemodynamically significant; in 6 subjects this type of lesion was present in
      both femoral and carotid arteries; in 5 the lesions were located in one carotid
      artery system, and in 2 in one femoral artery system. In conclusion, endurance
      exercise appears to protect the elderly against atherosclerotic vascular damage.

PMID- 9242161
TI  - Left-sided approach to renal cell carcinoma tumor thrombus extending into
      suprahepatic inferior vena cava by resection of the left caudate lobe.
AB  - A new operative approach to resecting tumor thrombus originating from a right
      renal cell carcinoma extending into the suprahepatic inferior vena cava (IVC) is
      reported. Complete local control of the IVC must be obtained above and below the
      tumor thrombus to remove it under direct vision. The caudate lobe of the liver
      was resected to expose the retrohepatic IVC and open the lesser omentum. The
      subhepatic IVC was encircled just below the confluence of the hepatic veins.
      Caval tumor thrombus was removed en bloc, including the right kidney, by use of
      the total hepatic vascular exclusion technique (THVE) and IVC exclusion. The
      retrohepatic IVC was clamped just below the confluence of the hepatic veins once
      the thrombus was removed, and the suprahepatic IVC clamp was then released and
      the THVE was terminated. The sequential clamping from the suprahepatic IVC to the
      retrohepatic IVC below the confluence of the hepatic veins shortened the THVE
      time.

PMID- 9242162
TI  - Leriche syndrome. Surgical procedures and early and late results.
AB  - During the past thirteen years, 29 patients underwent surgical intervention for
      Leriche syndrome. Fifteen patients (aged forty-two to seventy-two years, average
      60.7 years) underwent anatomical bypass, and 9 of them whose thrombus was
      confined to the infrarenal aorta received a routine graft insertion. In the other
      6 whose thrombus extended to the level of the renal arteries, an open
      thrombectomy of the juxtarenal aorta was first performed through a transection of
      the infrarenal aorta under renal ischemia (4-14 minutes, average 7). Twelve
      elderly or high-risk patients (aged sixty-eight to eighty-four years, average
      75.3 years) underwent an axillobifemoral bypass, and another 2 (fifty-eight and
      sixty years old, respectively) who had been operated on at an earlier time
      received an ascending aortobifemoral bypass. In cases of anatomical bypass, no
      graft has occluded and all patients but 1, who died of cerebral infarction, have
      an active life now. In cases of extraanatomical bypass, 5 of the 28 grafts
      occluded and only 6 patients have survived. The other 8 patients died of
      malignancy, atherosclerotic complications, or unknown causes. The 10-year
      survival rate was 92.9% and 29.5% in the anatomical bypass and extraanatomical
      bypass group, respectively. In Leriche syndrome, anatomical bypass is preferred
      to extraanatomical bypass if conditions permit. In the juxtarenal type, an open
      thrombectomy under renal ischemia is mandatory for anatomical bypass, and a
      transection of the infrarenal aorta facilitates this procedure. Because the
      patients with Leriche syndrome are elderly and harbor arteriosclerotic lesions, a
      careful follow-up is mandatory.

PMID- 9242163
TI  - Absent conal septum in tetralogy of Fallot. An angiographic study.
AB  - Absent conal septum in tetralogy of Fallot (TF) is usually noted intraoperatively
      when the ventricular septal defect (VSD) is found abutting the pulmonary valve,
      its superior rim being nearly inaccessible transatrially, and the posterior rim
      being separated from the tricuspid valve (TV) by a muscular ridge. The authors
      retrospectively analyzed angiograms of 208 consecutive patients with TF seen at
      their center from July 1989 to December 1995 for absence of the conal septum and
      the presence of an interval between the TV and the margin of the VSD in 30
      degrees right anterior oblique view. In 13 (6%) patients, angiograms were
      inadequate or of poor quality for assessment and were excluded. Twenty-two of the
      remaining 195 (11%) patients had a large muscular interval between the tricuspid
      annulus and the margin of the VSD, which was associated with an absent conal
      septum in 14 (7.2%) and a diminutive septum in 8 (4%) patients. Nine of the 14
      patients with an absent conal septum at angiography underwent surgery, and this
      finding was confirmed in all. The authors conclude that absent conal septum is
      not uncommon in TF and constitutes an important variation in its anatomy that can
      be identified preoperatively at angiography for optimal surgical management.

PMID- 9242164
TI  - Postoperative thrombosis of the superior caval vein in a patient with primary
      asymptomatic Behcet's disease. A case report.
AB  - Behcet's disease is a systemic vasculitis of unknown cause. In 1937 Behcet
      described 3 patients with oral and genital ulceration and hypopyon iritis. The
      disease shows worldwide distribution with the highest prevalence in the eastern
      Mediterranean region and Japan. The most common manifestation is recurrent oral
      ulceration. Other manifestations include genital ulceration, eye lesions, skin
      lesion, arthritis or arthralgia, and cerebral lesions. Venous thrombosis and
      thrombophlebitis are also recorded as manifestations. One of the causes of
      superior caval vein obstruction is Behcet's disease. Especially in Turkey, this
      association is common. Management must be directed against the primary disease
      plus the caval vein obstruction. The authors describe a patient with
      multisymptomatic presentation of Behcet's disease with thrombosis of the superior
      caval veins and successful lysis with streptokinase.

PMID- 9242165
TI  - Ambulatory blood pressure monitoring in diagnosing a pheochromocytoma of the
      urinary bladder. A case report.
AB  - A patient is presented in whom the preoperative diagnosis of an intravesical
      pheochromocytoma was facilitated by noninvasive ambulatory blood pressure
      monitoring. A fifty-two-year-old Japanese man suffered headache and palpitation
      after micturition. Cystoscopy revealed an intravesical tumor. To investigate
      whether his symptoms were associated with an elevation of blood pressure, the
      authors monitored his ambulatory blood pressure automatically for twenty-four
      hours. The patient was also instructed to activate the recording manually upon
      the onset of symptoms. As a result, elevations of blood pressure were apparent
      following micturition. The twenty-four-hour urinary excretion of norepinephrine
      was elevated on the day of the blood pressure monitoring. Pheochromocytoma was
      suspected and was confirmed by histopathologic studies following the operation.
      Thus, ambulatory blood pressure monitoring may be useful in detecting the
      transient hypertension induced by micturition, which can provide preoperative
      evidence of pheochromocytoma of the urinary bladder.

PMID- 9242166
TI  - Cervical aortic arch. A case report.
AB  - Cervical aortic arch is a rare type of aortic arch anomaly that is presumed to
      result from persistence of the third aortic arch and regression of the normal
      fourth arch. Most of the patients with this anomaly are asymptomatic, but
      symptoms of dysphagia and respiratory distress due to the compression by the
      vascular ring have been reported. Other findings such as a supraclavicular
      pulsatile mass, blood pressure discrepancies between the upper limbs, and loss of
      femoral or opposite-upper-limb pulses with compression of the cervical mass may
      also be present. In this article a twenty-two-year-old woman with symptomatic
      cervical aortic arch is presented. The patient had a left cervical pulsatile mass
      and elevated blood pressure on her right upper limb and was treated surgically
      with reanastomosis of the aorta.

PMID- 9242167
TI  - Quality-of-life management for cancer patients.
AB  - The importance of considering quality-of-life issues throughout the treatment of
      these cancers is evident. Although quality-of-life variables are being delineated
      for cancers of various organ systems, safeguarding the patient's sense of well
      being and self-esteem while preserving organ, endocrine, exocrine, and hormonal
      function, fosters the best possible quality of life for the patient in either a
      palliative or a curative setting. The next millennium will usher into practice
      more aggressive, targeted therapies that combine surgery, radiotherapy, and
      genetic and biologic agents. The proper sequencing, administration, and toxicity
      of these therapies will decrease morbidity and improve the quality of life for
      patients. Above all, the healthcare provider must be aware of the patient's
      personal concerns and needs for a good quality of life. The dictum espoused by
      Hippocrates of "primum non nocere" ("first, do no harm") is nowhere more
      appropriate than in the planning of individual therapies to achieve optimal
      quality of life.

PMID- 9242168
TI  - Quality-of-life management of patients with colorectal cancer.
AB  - We have reviewed management of the patient with colorectal cancer both after
      primary treatment and in the palliative setting. Although we have addressed
      quantitative measures of quality of life as applied to patients with colorectal
      cancer, the limitations of combining disparate variables that encompass
      morbidity, an idealized lifestyle, and personal variation in interpretation of
      that lifestyle into a single number or point on a graph are self-evident. The
      caring family physician has a better intuitive integration of patient complexity
      than does the outcomes analyst. When the apparently cured patient returns to the
      family physician after initial operative treatment, recovery is just beginning.
      We have addressed the morbidity of surgery, the role of adjuvant treatments, the
      short-term and long-term effects of adjuvant treatments on quality of life, and
      the management of these effects. Restoration of quality of life extends beyond
      cure or survival and embraces repair of the patient's confidence and psychosocial
      well-being. The patient with persistent or recurrent colorectal cancer merits the
      entire range of medical skills of the family physician. Not all patient findings
      arise from cancer; other treatable medical and surgical diseases occur. If
      findings are from recurrent colorectal cancer, the patient may still be curable
      by treatment or may enjoy prolonged quality of life with or without anticancer
      treatment. Do not rush to judgment about remaining life span. Although pain
      control is the benchmark of palliative care, psychological elements that affect
      severity of pain and the invariably associated depression of the patient require
      the emotional support and compassion of the family physician.

PMID- 9242169
TI  - Quality of life in prostate cancer patients.

PMID- 9242170
TI  - Quality of life in gynecologic cancer survivors.

PMID- 9242171
TI  - Limb-salvage strategies to optimize quality of life: the M.D. Anderson Cancer
      Center experience.

PMID- 9242172
TI  - An adjustment to the 1997 estimate for new prostate cancer cases.

PMID- 9242173
TI  - Adjuvant therapy for colon cancer.
AB  - Adjuvant therapy for colon cancer is now a mature and widely accepted standard of
      care for patients with resected large bowel tumors: adjuvant therapy for stage
      III colon cancer has also been shown to be highly cost-effective. The cost of 5
      FU/levamisole therapy for stage III colon cancer per year of life saved is less
      than $ 5,000, which represents a favorable cost-benefit relationship for a
      medical intervention. The clinician managing a patient with colon cancer at the
      present time has several options for therapy. In patients with stage III colon
      cancer, therapy with 5-FU-based regimens clearly increases overall and disease
      free survival. It is also clear that the results that have been obtained are not
      perfect; therefore, the first option of therapy should always be an ongoing
      clinical trial. Many such trials are available, and Table 7 lists currently
      active studies in the United States. The clinician managing a patient with stage
      III colon cancer who is not in a clinical trial may choose a variety of regimens
      administered for durations of 6 to 12 months (Table 8). The preponderance of
      evidence suggests that 5-FU plus levamisole for 12 months is equal in efficacy to
      5-FU plus leucovorin-based regimens given for a shorter period of time. A
      clinician may still choose the 5-FU plus levamisole regimen because of the
      decreased oral, myelosuppressive, and diarrheal toxicities associated with that
      regimen as opposed to the 5-FU/leucovorin regimens. Portal vein infusion of
      fluorinated pyrimidines still must be considered investigational. Finally,
      although we cannot be absolutely sure about the benefit of adjuvant therapy in
      patients with resected node-negative colon cancer, the NSABP data suggest that
      some benefit may be seen in these patients. It is known that patients with stage
      II cancers demonstrating high-grade bowel obstruction or bowel perforation have
      poor prognoses with surgery alone. Such patients may be good candidates for
      adjuvant therapy. Also, a major effort to define high risk and low risk for
      recurrence in patients with stage II colon cancer by analyzing molecular genetic
      factors (tumor ploidy and alternations in tumor suppressor genes) may lead to a
      selection of Dukes B patients definitely requiring adjuvant therapy.

PMID- 9242174
TI  - Death by design. Programmed cell death in cardiovascular biology and disease.
AB  - Programmed cell death (apoptosis) is recognized, increasingly, as a contributing
      cause of cardiac myocyte loss with ischemia/reperfusion injury, myocardial
      infarction, and long-standing heart failure. Although the exact mechanisms
      initiating apoptosis in these in vivo settings remain unproven, insights into the
      molecular circuitry controlling apoptosis more widely suggest the potential to
      protect mammalian ventricular muscle from apoptosis through one or more of these
      pathways, by pharmacological means or, conceivably, gene transfer.

PMID- 9242175
TI  - Adenoviral gene transfer of phospholamban in isolated rat cardiomyocytes. Rescue
      effects by concomitant gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase.
AB  - Phospholamban forms an integral part of the cardiac sarcoplasmic reticulum (SR)
      and regulates the activity of SR Ca(2+)-ATPase (SERCA2a). A number of studies
      have suggested a decrease in SERCA2a relative to phospholamban in heart failure.
      To test the hypothesis that changes in the relative abundance of phospholamban to
      SERCA2a could account for the pathophysiological abnormalities in Ca2+ handling
      observed in failing myocardium, we created a recombinant adenovirus designed to
      overexpress phospholamban (Ad.RSV.PL). In neonatal rat cardiomyocytes, Ad.RSV.PL
      increased the expression of phospholamban in a concentration-dependent fashion,
      reaching 280 +/- 43% at a multiplicity of infection (MOI) of 10.0 plaque forming
      units (pfu)/cell at 48 hours. The relationship between Ca(2+)-ATPase activity and
      [Ca2+] was shifted rightward in membrane preparations from cardiomyocytes
      infected with Ad.RSV.PL. Intracellular Ca2+ transients measured in the neonatal
      cells infected with Ad.RSV.PL (MOI, 10 pfu/cell) were characterized by (1) a
      significant prolongation of the relaxation phase (344 +/- 26 versus 710 +/- 56
      milliseconds, P < .01), (2) a decrease in peak [Ca2+]i (967 +/- 43 versus 630 +/-
      33 nmol/L, P < .01), and (3) an elevation in resting [Ca2+]i (143 +/- 14 versus
      213 +/- 17 nmol/L, P < .05). Similarly, the time course of shortening was
      prolonged in myocytes infected with Ad.RSV.PL. These effects were partially
      restored by simultaneous transduction with an adenovirus carrying SERCA2a.
      Cardiomyocytes infected with Ad.RSV.PL had an abnormal frequency response: a
      decrease in peak [Ca2+]i and an increase in resting [Ca2+]i with increasing
      frequency. These findings indicate that adenovirus-mediated gene transfer of
      phospholamban modifies intracellular Ca2+ handling and the frequency response in
      cardiomyocytes. Our results suggest that alterations in the ratio of
      phospholamban to SERCA2a could account for the abnormalities in Ca2+ handling
      observed in heart failure and that overexpression of SERCA2a can largely correct
      these abnormalities.

PMID- 9242176
TI  - Hypoxia-induced inhibition of adenosine kinase potentiates cardiac adenosine
      release.
AB  - To elucidate the physiological role of the AMP-adenosine metabolic cycle and to
      investigate the relation between AMP and adenosine formation, the O2 supply of
      isolated guinea pig hearts was varied (95% to 10% O2). The net adenosine
      formation rate (AMP-->adenosine) and coronary venous effluent adenosine release
      rate were measured; free cytosolic AMP was determined by 31P-nuclear magnetic
      resonance. Switching from 95% to 40% O2 increased free AMP and adenosine
      formation 4-fold, whereas free cytosolic adenosine and venous adenosine release
      rose 15- to 20-fold. In the AMP range from 200 to 3000 nmol/L, there was a linear
      correlation between free AMP and adenosine formation (R2 = .71); however,
      adenosine release increased several-fold more than formation. At 95% O2, only 6%
      of the adenosine formed was released; however, this fraction increased to 22% at
      40% O2, demonstrating reduced adenosine salvage. Selective blockade of adenosine
      deaminase and adenosine kinase indicated that flux through adenosine kinase
      decreased from 85% to 35% of adenosine formation in hypoxia. Mathematical model
      analysis indicated that this apparent decrease in enzyme activity was not due to
      saturation but to the inhibition of adenosine kinase activity to 6% of the basal
      levels. The data show (1) that adenosine formation is proportional to the AMP
      substrate concentration and (2) that hypoxia decreases adenosine kinase activity,
      thereby shunting myocardial adenosine from the salvage pathway to venous release.
      In conclusion, because of the normal high turnover of the AMP-adenosine metabolic
      cycle, hypoxia-induced inhibition of adenosine kinase causes the amplification of
      small changes in free AMP into a major rise in adenosine. This mechanism plays an
      important role in the high sensitivity of the cardiac adenosine system to
      impaired oxygenation.

PMID- 9242177
TI  - Altered metabolite exchange between subcellular compartments in intact
      postischemic rabbit hearts.
AB  - To examine metabolic regulation in postischemic hearts, we examined oxidative
      recycling of 13C within the glutamate pool (GLU) of intact rabbit hearts.
      Isolated hearts oxidized 2.5 mmol/L [2-13C]acetate during normal conditions (n =
      6) or during reperfusion after 10 minutes of ischemia (n = 5). 13C-Nuclear
      magnetic resonance spectra were acquired every 1 minute. Kinetic analysis of 13C
      incorporation into GLU provided both tricarboxylic acid (TCA) cycle flux and the
      interconversion rate (F1) between the TCA cycle intermediate, alpha-ketoglutarate
      (alpha-KG), and the largely cytosolic GLU. The rate-pressure product in
      postischemic hearts was 46% of normal (P < .05). No difference in substrate
      utilization occurred between groups, with acetate accounting for 92% of the
      carbon units entering the TCA cycle at the citrate synthase step. TCA cycle flux
      in postischemic hearts was normal (normal hearts, 10.7 mumol.min-1.g-1;
      postischemic hearts, 9.4 mumol.min-1.g-1), whereas F1 was 72% lower at 2.9 +/-
      0.4 versus 10.2 +/- 2.5 mumol.min-1.g-1 (mean +/- SE) in normal hearts (P < .05).
      From additional hearts perfused with 2.5 mmol/L [2-13C]acetate plus supplemental
      5 mmol/L glucose, any potential differences in endogenous carbohydrate
      availability were proved not to account for the reduced rate alpha-KG and GLU
      exchange, which remained depressed in postischemic hearts. However, specific
      activities of the transaminase enzyme, catalyzing chemical exchange of alpha-KG
      and GLU, were the same, and transaminase flux was 100 mumol.min-1.g-1 in
      postischemic hearts versus 68 mumol.min-1.g-1 in normal hearts. Normal
      transaminase activity and the increased flux in postischemic hearts are contrary
      to the reduced F1. The findings indicate reduced metabolite transport rates
      across the mitochondrial membranes of stunned myocardium, particularly through
      the reversible alpha-KG-malate carrier.

PMID- 9242178
TI  - Rapamycin inhibits alpha 1-adrenergic receptor-stimulated cardiac myocyte
      hypertrophy but not activation of hypertrophy-associated genes. Evidence for
      involvement of p70 S6 kinase.
AB  - The 70-kD S6 kinase (p70S6K) has been implicated in the regulation of protein
      synthesis in many cell types and in the angiotensin II-stimulated hypertrophy of
      cardiac myocytes. Our purpose was to determine whether p70S6K plays a role in
      cardiomyocyte hypertrophy induced by the alpha 1-adrenergic receptor (alpha 1-AR)
      agonist phenylephrine (PE). PE stimulated the activity of p70S6K > 3-fold, and
      this increase was blocked by rapamycin, an immunosuppressant macrolide that
      selectively inhibits p70S6K. When administered for 3 days, PE stimulated a 30%
      increase in total protein content, a 2-fold increase in the incorporation of
      [14C]phenylalanine (14C-Phe) into protein, and a 50% increase in two-dimensional
      myocyte area. Rapamycin pretreatment (> or = 500 pg/mL) significantly inhibited
      each of these PE-stimulated changes. Two days of PE treatment resulted in a 1.6
      fold increase in total RNA yield per dish, a 2-fold increase in incorporation of
      [14C]uridine into myocyte RNA, and increases in relative mRNA levels of the
      hypertrophy-associated atrial natriuretic factor (ANF, 2.1-fold) and skeletal
      alpha-actin (SK, 2.2-fold) genes. Although rapamycin abolished the PE-stimulated
      increases in total RNA and incorporation of [14C]uridine, it had no effect on the
      induction of the ANF and SK genes. LY294002, a specific inhibitor of
      phosphatidylinositol 3-kinase (PI3-K) activity, inhibited PE-stimulated increases
      in p70S6K activity and the incorporation of labeled precursors into myocyte
      protein and RNA. These results demonstrate that p70S6K is activated by the
      hypertrophic agent PE and that a PI3-K or PI3-K-like activity is required for
      p70S6K activation and myocyte hypertrophy. The data suggest that p70S6K
      activation may be required for PE-stimulated hypertrophy of cardiac myocytes. Our
      results demonstrate that intracellular signaling pathways responsible for
      transcriptional and translational responses diverge early after alpha 1-AR
      stimulation in cardiac myocytes.

PMID- 9242180
TI  - Emigrated rat neutrophils adhere to cardiac myocytes via alpha 4 integrin.
AB  - Previous work has shown that neutrophils isolated from whole blood adhere to
      cardiac-myocytes via CD18 (beta 2 integrin) to cause injury to the heart cells.
      In vitro, we have found that upon endothelial transmigration, neutrophils can
      also express alpha 4 beta 1; however, whether this contributes to neutrophil
      adhesion to parenchymal cells remains entirely unknown. Unstimulated and tumor
      necrosis factor-alpha-stimulated rat cardiac myocytes adherent to gelatin-coated
      coverslips supported N-formyl-Met-Leu-Phe (fMLP)-induced neutrophil (isolated
      from whole blood) adhesion entirely via CD18 (blocked with monoclonal antibody
      [mAb] WT-3). Emigrated neutrophils spontaneously adhered to cardiac myocytes also
      entirely via CD18. However, if fMLP was used to restimulate emigrated
      neutrophils, the adhesion to cardiac myocytes was entirely independent of CD18.
      Although an anti-alpha 4 integrin antibody (mAb TA-2) alone did not reduce the
      emigrated neutrophil-myocyte interaction, dual administration of TA-2 and WT-3
      reduced adhesion by 81%. alpha 4 integrin was expressed in small amounts on the
      surface of circulating neutrophils, increased following transmigration, and then
      increased > 5-fold after restimulation of these emigrated neutrophils. In the
      presence of the anti-CD18 antibody, a fibronectin fragment (FN-40) but not a
      vascular cell adhesion molecule-1 antibody (mAb 5F10) inhibitied neutrophil
      myocyte interactions by 80%. Similar results were seen when the rat chemokine
      CINC-gro was used instead of fMLP, suggesting that the alpha 4-dependent adhesion
      was not specific to fMLP. These data demonstrate that alpha 4 integrin can be
      physiologically induced to increase in number and avidity after neutrophil
      emigration and that this adhesion molecule can cause firm adhesion to fibronectin
      on parenchymal cells, including rat cardiac myocytes.

PMID- 9242179
TI  - Hemodynamic regulation of tumor necrosis factor-alpha gene and protein expression
      in adult feline myocardium.
AB  - Tumor necrosis factor-alpha (TNF-alpha) mRNA and protein biosynthesis were
      examined in adult feline myocardium in the presence and absence of superimposed
      hemodynamic pressure overloading. A brief period of hemodynamic pressure
      overloading ex vivo resulted in de novo TNF-alpha mRNA expression within 30
      minutes and de novo TNF-alpha protein production within 60 minutes; neither TNF
      alpha mRNA nor protein was detected in hearts perfused at normal perfusion
      pressures. Moreover, TNF-alpha mRNA and protein biosynthesis were observed in
      myocyte and nonmyocyte cell types in the pressure-overloaded hearts. To determine
      whether a simple passive stretch of the myocardium was a sufficient stimulus for
      TNF-alpha biosynthesis, we examined TNF-alpha mRNA expression in stretched and
      unstretched papillary muscles. This study showed that myocardial stretch was a
      sufficient stimulus for the induction of TNF-alpha mRNA biosynthesis. The
      functional significance of the intramyocardial production of TNF-alpha was
      determined by examining cell motion in isolated contracting cardiac myocytes
      treated with superfusates from pressure-overloaded and control hearts. These
      studies showed that cell motion was depressed in myocytes treated with
      superfusates from the pressure-overloaded hearts but was normal with the
      superfusates from the control hearts. Finally, hemodynamic pressure overloading
      in vivo under physiological conditions was also shown to result in de novo
      intramyocardial TNF-alpha mRNA biosynthesis. In conclusion, this study
      constitutes the initial demonstration that the adult mammalian myocardium
      elaborates biologically active TNF-alpha, both ex vivo and in vivo, in response
      to hemodynamic pressure overloading.

PMID- 9242181
TI  - Inhibition of L-type Ca2+ channel current in rat ventricular myocytes by
      terfenadine.
AB  - To elucidate possible mechanisms underlying the cardiotoxicity of terfenadine,
      the effect of this antihistamine on L-type Ca2+ channel current (ICa,L) was
      studied in adult rat ventricular myocytes using the whole-cell patch-clamp
      technique. Myocytes were held at -70 mV and internally dialyzed and externally
      perfused with Na(+)- and K(+)-free solutions; exposure to terfenadine (10(-9) to
      5 x 10(-6) mol/L) resulted in a concentration-dependent inhibition of peak ICa,L
      with a half-maximum inhibition concentration (IC50) of 142 nmol/L. The
      terfenadine-induced inhibition of ICa,L was not mediated via effects on histamine
      H1 receptors, because 1 mumol/L triprolidine, a more selective and potent H1
      antagonist, had no effect on ICa,L. In this study, we found that terfenadine (1)
      increased both the fast and slow time constants of ICa,L inactivation, (2)
      shifted the steady state inactivation of ICa,L to more negative potentials, and
      (3) elicited a tonic block and a use-dependent block of ICa,L. The terfenadine
      induced tonic and use-dependent block and the steady state inhibition of ICa,L
      were voltage dependent. Both tonic and use-dependent blocks of ICa,L by
      terfenadine at -40 mV were greater than that at -70 mV, and blocks were partially
      released by applying a long hyperpolarizing prepulse to -90 mV. These results
      suggest that terfenadine binds to L-type Ca2+ channels in inactivated and rested
      states and inhibits ICa,L predominantly by interacting with the inactivated state
      with an apparent dissociation constant of 60 nmol/L. Open-state block could be
      observed only at high concentrations of terfenadine. The high-affinity
      interaction of terfenadine with the inactivated state of L-type Ca2+ channels may
      play an important role in its cardiotoxicity under pathophysiological conditions,
      such as ischemia.

PMID- 9242182
TI  - Endothelin-1 inhibits the slow component of cardiac delayed rectifier K+ currents
      via a pertussis toxin-sensitive mechanism.
AB  - Endothelin-1 (ET-1) is a 21-amino acid peptide hormone released from myocardial
      and endothelial cells, whose receptors (both ETA and ETB are expressed in the
      myocardium. We report here that ET-1 inhibits the cardiac delayed rectifier K+
      current (IK) via a pertussis toxin (PTX)-sensitive mechanism. Ventricular
      myocytes enzymatically isolated from guinea pig hearts were voltage-clamped by
      the conventional whole-cell and nystatin-perforated patch technique (intrapipette
      and extrapipette K+ concentrations, 150 and 5.4 mmol/L, respectively) in the
      presence of nifedipine (2 mumol/L). Amplitudes of tail and steady state (2-second
      pulse) currents were measured as IK. ET-1 suppressed the basal IK by 20.9 +/-
      2.3% in a concentration-dependent manner, with an IC50 of 1.1 +/- 0.3 nmol/L (n =
      19), although it did not suppress the basal IK using the nystatin method. E-4031
      (5 mumol/L), a blocker of the rapid component of IK (IKr), did not prevent the
      inhibitory action of ET-1. ET-1 reduced by 63.4 +/- 6.5% the slow component of IK
      (IKs) that had been enhanced to approximately 2-fold by isoproterenol (ISO, 20
      nmol/L). The action was concentration dependent, with an IC50 of 0.7 +/- 0.4
      nmol/L (n = 22), and was also observed using the nystatin method. The effect of
      ET-1 appeared to be mediated by an ETA receptor, because it was prevented by
      FR139317, an ETA-selective antagonist (1 mumol/L, n = 4), and sarafotoxin s6c, an
      ETB-selective agonist (100 nmol/L, n = 4), could not inhibit the ISO-enhanced IK.
      ET-1 antagonized IKs enhanced by histamine (250 nmol/L, n = 7) and forskolin (500
      nmol/L, n = 7) but did not inhibit IKs enhanced by the internal application of
      cAMP (100 mumol/L, n = 6). Preincubation of myocytes with PTX (5 micrograms/mL
      for > 60 minutes at 36 degrees C) completely abolished the inhibitory action of
      ET-1 on the ISO-enhanced IKs (n = 4). Thus, nanomolar ET-1 inhibits IKs via the
      ETA receptor/PTX-sensitive G protein/PKA pathway.

PMID- 9242183
TI  - Phosphatase-mediated enhancement of cardiac cAMP-activated Cl-conductance by a Cl
      channel blocker, anthracene-9-carboxylate.
AB  - An aromatic carboxylate, anthracene-9-carboxylic acid (9-AC), is known as a Cl-
      channel blocker. However, variable 9-AC effects have hitherto been reported on
      the cardiac cAMP-activated Cl- conductance, when applied extracellularly. We have
      reexamined the 9-AC effect on the Cl-conductance activated by isoproterenol or
      forskolin in guinea pig ventricular myocytes under whole-cell patch-clamp
      conditions. The inward current was blocked by 9-AC at > or = 0.5 mmol/L, but in
      contrast, the outward current was enhanced at much lower concentrations (ED50,
      approximately 13 mumol/L). 9-AC applied by the intracellular perfusion technique
      increased both the inward and outward currents. In the presence of intracellular
      9-AC, deactivation of the conductance after washout of isoproterenol or forskolin
      was largely prevented. 9-AC produced an enhancing effect, even after inhibiting
      the deactivation process by okadaic acid (OA), whereas it failed to produce
      additional-effects in the presence of orthovanadate. Intracellular application of
      9-AC together with OA virtually abolished the current deactivation. The 9-AC
      effects on the Cl-conductance were not dependent on intracellular Ca2+ or pH.
      Putative inhibitors of alkaline (bromotetramisole) and acid phosphatases
      (tartrate) were without effect. 9-AC failed to inhibit the activities of purified
      protein phosphatase (PP)-1, -2A, and -2C. In the extract of guinea pig ventricle,
      9-AC (> or = 10 mumol/L for full action) significantly inhibited a fraction of
      endogenous phosphatase activity that was sensitive to orthovanadate but not to
      OA, bromotetramisole, and tartrate. It is concluded that 9-AC blocks cardiac cAMP
      activated (cystic fibrosis transmembrane conductance regulator) Cl- conductance
      from the extracellular side but enhances the conductance from the intracellular
      side by inhibiting an orthovanadate-sensitive phosphatase distinct from PP-1, 
      2A, -2B, or -2C and alkaline or acid phosphatase.

PMID- 9242184
TI  - Line stimulation parallel to myofibers enhances regional uniformity of
      transmembrane voltage changes in rabbit hearts.
AB  - The sign of transmembrane voltage (Vm) change (delta Vm) in the heart during
      unipolar point stimulation is nonuniform, which introduces dispersion of states
      of Vm-dependent ion channels that depends on fiber orientation. We hypothesized
      that line stimulation parallel to cardiac fibers increases regional uniformity of
      the delta Vm sign. To test this, we evaluated electrode current distribution and
      delta Vm produced by unipolar line stimulation in isolated rabbit hearts. The Vm
      sensitive fluorescent dye, di-4-ANEPPS, and a laser scanner provided delta Vm
      measurements at 63 spots in an 8 x 8-mm epicardial region. Line stimulation was
      tested at specific angles with respect to the fiber direction. Current peaks
      occurred at electrode ends. For electrodes parallel to fibers (0 degree),
      epicardium in regions beyond the ends exhibited a nonuniform delta Vm sign,
      whereas epicardium between the ends exhibited a uniform delta Vm sign that was
      essentially negative (hyperpolarized) during anodal pulses and positive
      (depolarized) during cathodal pulses. The delta Vm sign between the ends became
      less uniform when the stimulation angle was increased relative to the long axis
      of the fibers. At 90 degrees, the delta Vm sign between the ends was nonuniform
      and was frequently opposite, near versus away from the electrode. Spatial
      distributions of delta Vm during line stimulation were qualitatively predictable
      from anisotropic effects of point stimulation provided that combined effects of
      points along the electrode and points with higher current near ends were
      considered. For biphasic line stimulation, delta Vm during the second phase was
      weakly correlated with the temporal sum of effects of phases given individually,
      indicating limited ability of summation to predict delta Vm. Thus, uniformity of
      the delta Vm sign during stimulation is enhanced in the region between the ends
      of a line electrode parallel to fibers. This may lessen arrhythmogenic dispersion
      of Vm-dependent ion channel states in the region.

PMID- 9242185
TI  - Mechanism of vascular smooth muscle relaxation by estrogen in depolarized rat and
      mouse aorta. Role of nuclear estrogen receptor and Ca2+ uptake.
AB  - 17 beta-Estradiol induces vasodilation in vitro and in vivo, which has been
      suggested to contribute to the cardiovascular protection by this ovarian steroid
      hormone. However, the exact mechanism of vasorelaxation by estrogens remains to
      be elucidated. In this study, we analyzed the potential role of genomic
      mechanisms involving the nuclear estrogen receptor and inhibition of entry of
      extracellular Ca2+ in 17 beta-estradiol-induced vasorelaxation in depolarized
      aortic rings, isolated from male and female rats and male mice. In both male and
      female rat aortic rings without endothelium and in intact male mouse aortic rings
      treated with NG-nitro-L-arginine, 17 beta-estradiol caused dose-dependent (0.3 to
      30 mumol/L) relaxation of contraction evoked by high-K+ depolarization (30 and 45
      mmol/L KCl, respectively). The estrogen receptor antagonist ICI 164384 had no
      effect on 17 beta-estradiol-induced relaxations. 125I-17 beta-estradiol binding
      studies showed the presence of high-affinity cytosolic-nuclear estrogen receptors
      in control male mouse aortas. Comparable relaxations of aortic rings isolated
      from control and estrogen receptor-deficient transgenic mice provided direct
      evidence that the nuclear estrogen receptor is not involved in this response. 17
      beta-Estradiol-induced relaxation of rat aortic rings could not be prevented by
      cycloheximide or actinomycin D, suggesting that the response was not mediated by
      de novo protein synthesis or gene transcription. In rat aortic rings, 17 beta
      estradiol inhibited the increase of 45Ca uptake by 30 mmol/L KCl at
      concentrations (10 and 30 mumol/L) that caused vasorelaxation in the same tissue,
      suggesting that inhibition of Ca2+ entry contributes to the response. 17 alpha
      Estradiol was less effective, and estrone was devoid of vasorelaxing activity.
      Vasorelaxation by estrogens in female and male rat aortas was similar, indicating
      no gender difference in vascular responses under these conditions.

PMID- 9242186
TI  - Angiotensin II activates phosphatidylinositol 3-kinase in vascular smooth muscle
      cells.
AB  - Phosphatidylinositol 3-kinase (PI3K) is an important component of the signal
      transduction systems activated by tyrosine kinase receptors. It has not been
      established, however, whether PI3K is also an essential mediator for G protein
      coupled receptors. The potential involvement of PI3K in G protein-linked
      angiotensin II (Ang II)-dependent signaling was assessed in a primary cell
      culture system of porcine coronary artery smooth muscle cells (SMCs). Treatment
      of quiescent SMCs with Ang II (10(-5) to 10(-8) mol/L) resulted in a dose
      dependent activation of PI3K when assayed in vivo and in vitro. The Ang II
      receptor antagonists losartan and PD123319 were used to establish that Ang II
      stimulates PI3K through the Ang II type-1 (AT1) receptor. Immunofluorescent
      microscopy revealed that Ang II (10(-6) mol/L) stimulated the translocation of
      p85, the regulatory subunit of PI3K, from the perinuclear region to distinct foci
      throughout the cell within 15 minutes. Western blot analysis of p85 subcellular
      distribution demonstrated that p85 concentrations were also increased within 15
      minutes in the membrane fraction and concomitantly decreased in the cytoskeletal
      and nuclear fractions. These changes in PI3K location and activity were
      paralleled by increased tyrosine phosphorylation of p85. A potential correlation
      between angiotensin-mediated PI3K activation and SMC growth was found using
      LY294002, a specific inhibitor of PI3K, which blocked the increase in DNA and RNA
      synthesis as well as cellular hyperplasia generated by Ang II (10(-6) mol/L)
      stimulation of quiescent SMCs. These data indicate that PI3K may operate as a
      mediator of vascular SMC growth after stimulation with Ang II.

PMID- 9242188
TI  - Angiotensin II stimulates p90rsk in vascular smooth muscle cells. A potential
      Na(+)-H+ exchanger kinase.
AB  - Angiotensin II is a multifunctional agonist for vascular smooth muscle cells
      (VSMCs), stimulating increases in signal events, cell growth, and ion flux. We
      previously defined protein kinase C (PKC)-dependent and -independent mechanisms
      by which angiotensin II stimulated activity of the Na(+)-H+ exchanger isoform-1
      (NHE-1) and identified a 90-kD kinase that exhibited increased activity in VSMCs
      isolated from genetically hypertensive rats. To determine whether this 90-kD
      kinase was p90rsk (RSK), VSMCs were stimulated with 100 nmol/L angiotensin II,
      and NHE-1 kinase activity was measured by phosphorylation of recombinant NHE-1 (a
      glutathione S-transferase fusion protein containing amino acids 516 to 815 of the
      cytoplasmic carboxyl tail) in vitro. NHE-1 kinase (90 kD) activity was markedly
      decreased by immunodepletion of RSK. Characterization of RSK activation by
      angiotensin II revealed many similarities to the 90-kD NHE-1 kinase, including
      time course and NHE-1 domain phosphorylation, as well as regulation by
      extracellular signal-regulated kinases (ERK1/2), intracellular Ca2+, and PKC.
      Specifically, angiotensin II stimulated a rapid and transient (peak, 5 minutes)
      increase in RSK activity. Analysis of several NHE-1 fusion proteins revealed that
      only proteins containing amino acids 670 to 714 were phosphorylated by RSK.
      Inhibiting ERK1/2 (30 mumol/L PD098059 for 30 minutes) or chelating intracellular
      Ca2+ prevented RSK activation. In contrast, downregulating PKC (1 mumol/L phorbol
      dibutyrate for 24 hours) had little effect. These findings establish RSK as a
      putative NHE-1 kinase and potential mediator of increased Na(+)-H+ exchange in
      hypertension.

PMID- 9242187
TI  - Potentiation of endothelium-dependent relaxation by epoxyeicosatrienoic acids.
AB  - Epoxyeicosatrienoic acids (EETs) are potent endothelium-derived vasodilators
      formed from cytochrome P-450 metabolism of arachidonic acid. EETs and their diol
      products (DHETs) are also avidly taken up by endothelial cells and incorporated
      into phospholipids that participate in signal transduction. To investigate the
      possible functional significance of EET and DHET incorporation into cell lipids,
      we examined the capacity of EETs and DHETs to relax porcine coronary arterial
      rings and determined responses to bradykinin (which potently activates
      endothelial phospholipases) before and after incubating the rings with these
      eicosanoids. 14,15-EET and 11,12-EET (5 mumol/L) produced 75 +/- 9% and 52 +/- 4%
      relaxation, respectively, of U46619-contracted rings, whereas 8,9-EET and 5,6-EET
      did not produce significant relaxation. The corresponding DHET regioisomers
      produced comparable relaxation responses. Preincubation with 14,15-EET, 11,12
      EET, 14,15-DHET, and 11,12-DHET augmented the magnitude and duration of
      bradykinin-induced relaxation, whereas endothelium-independent relaxations to
      aprikalim and sodium nitroprusside were not potentiated. Pretreatment with 2
      mumol/L triacsin C (an inhibitor of acyl coenzyme A synthases) inhibited
      [3H]14,15-EET incorporation into endothelial phospholipids and blocked 11,12-EET-
      and 14,15-DHET-induced potentiation of relaxation to bradykinin. Exposure of
      [3H]14,15-EET-labeled endothelial cells to the Ca2+ ionophore A23187 (2 mumol/L)
      resulted in a 4-fold increased release of EET and DHET into the medium. We
      conclude that incorporation of EETs and DHETs into cell lipids results in
      potentiation of bradykinin-induced relaxation in porcine coronary arteries,
      providing the first evidence that incorporated EETs and DHETs are capable of
      modulating vascular function.

PMID- 9242189
TI  - Low-density lipoprotein receptor knockout mice exhibit exaggerated microvascular
      responses to inflammatory stimuli.
AB  - The objective of this study was to determine whether genetically induced
      hypercholesterolemia affects leukocyte-endothelial cell interactions in
      postcapillary venules of the mouse cremaster muscle. Leukocyte adhesion,
      emigration, and other microvascular parameters were assessed in venules of normal
      (wild-type) and low-density lipoprotein receptor-deficient (LDLr-/-) mice
      maintained on either normal rodent chow or on a high cholesterol diet (HCD).
      Measurements were obtained under control conditions and after administration of
      either leukotriene B4 (LTB4), platelet-activating factor (PAF), or tumor necrosis
      factor-alpha (TNF-alpha). Elevated numbers of adherent and emigrated leukocytes
      were observed in venules of LDLr-/- (compared with wild-type) mice on HCD, both
      under baseline conditions and after exposure to either LTB4, PAF, or TNF-alpha.
      Plasma TNF-alpha levels were also elevated in LDLr-/- versus wild-type mice.
      Administration of blocking monoclonal antibodies demonstrated that intercellular
      adhesion molecule-1, but not vascular cell adhesion molecule-1, mediates the
      exaggerated leukocyte-endothelial cell adhesion observed in LDLr-/- mice. The
      results of these studies indicate that chronic hypercholesterolemia predisposes
      the microvasculature to intense leukocyte-endothelial cell adhesion in response
      to different inflammatory stimuli.

PMID- 9242191
TI  - Exocytosis in excitable cells: a conserved molecular machinery from yeast to
      neuron.
AB  - One of the basic cellular functions of nearly every cell type is the exocytotic
      release of synthesized molecules, stored and packaged into intracellular vesicles
      or granules. A variety of approaches has been used to identify and characterize
      the molecules that mediate vesicular trafficking along the secretory pathway. The
      findings obtained with these approaches suggest that common mechanisms may
      underlie a wide variety of vesicle-mediated transport steps. This review presents
      some of the recent findings regarding the study of the cellular mechanisms which
      control neurotransmitter and hormone release from neurons and endocrine cells
      respectively, and focuses on regulation of these mechanisms. The similarities
      between these two cell types can be seen as evidence to support the hypothesis
      according to which the regulated exocytosis apparatus could have evolved from a
      constitutive fusion machinery to which some key modulators have been added.
      Insight into secretory vesicles will be relevant not only to the understanding of
      vesicular trafficking or cell polarity but also to the understanding of higher
      nervous functions resulting from synaptic plasticity.

PMID- 9242190
TI  - FGF-1-induced platelet-derived growth factor-A chain gene expression in
      endothelial cells involves transcriptional activation by early growth response
      factor-1.
AB  - Fibroblast growth factor-1 (FGF-1), a prototype member of the heparin-binding
      growth factor family, is a potent mitogen for vascular endothelial cells and a
      variety of other cell types. FGF-1 can induce the expression of the platelet
      derived growth factor-A chain (PDGF-A) gene in endothelial cells; however, the
      underlying transcriptional mechanisms are not known. We used serial 5' deletion
      and transient transfection analysis of the human PDGF-A promoter to demonstrate
      that a 16-bp element, located 55 to 71 bp upstream of the transcriptional start
      site, is required for FGF-1-inducible promoter-dependent expression. This region
      contains nucleotide recognition elements for the early growth response gene
      product, early growth response factor-1 (Egr-1), and the related zinc-finger
      transcription factor, Sp1. Reverse-transcription polymerase chain reaction
      revealed that FGF-1 induced Egr-1 mRNA expression within 30 minutes.
      Electrophoretic mobility shift, supershift, and Western blot analysis
      demonstrated that Egr-1 protein accumulated in the nuclei of endothelial cells
      exposed to the growth factor, whereas levels of Sp1 did not change. Egr-1 bound
      to the FGF-1 response element in the proximal PDGF-A promoter in a specific and
      time-dependent manner. These findings indicate that Egr-1 plays a key regulatory
      role in FGF-1-inducible endothelial PDGF-A expression and implicate this
      transcription factor in pathological settings in which these mitogens are both
      expressed.

PMID- 9242192
TI  - The expanding world of primary adrenal insufficiencies.

PMID- 9242193
TI  - Gestational diabetes: a continuum of risk.

PMID- 9242195
TI  - Sensing hypoglycemia: the ventromedial hypothalamus.

PMID- 9242194
TI  - Towards an animal model of amiodarone-induced thyroid dysfunction.

PMID- 9242196
TI  - Molecular insights into the regulation of energy intake and expenditure.

PMID- 9242197
TI  - Update on the thyroid sodium iodide symporter: a novel thyroid antigen emerging
      on the horizon.

PMID- 9242198
TI  - Risk factors for fetal macrosomia: the importance of a positive oral glucose
      challenge test.
AB  - OBJECTIVE: The aim of this study was to investigate whether minor abnormalities
      of glucose metabolism without gestational diabetes are a risk factor for fetal
      overgrowth. DESIGN: A sample of 1883 unselected white mother-infant pairs were
      screened for gestational diabetes using a 50 g 1-h oral glucose challenge test
      (GCT) in two periods of pregnancy: early (16-20 weeks) and late (26-30 weeks).
      METHODS: The effects of risk factors (glucose metabolism, previous history of
      mothers, obesity, multiparity and age of mothers) were estimated using a
      multinomial logit model. RESULTS: The level of risk was related to gestational
      age at the appearance of an abnormal GCT. Patients with an abnormal GCT in the
      early and late periods of pregnancy (Group 1) had a risk of delivering a large
      for gestational age (LGA) infant seven times higher than the control group
      (normal GCT in both periods), and patients with a normal GCT in the early period
      and an abnormal GCT in the late period (Group 2) showed a risk three times higher
      than the control group. Among the historical risk factors for LGA infants, such
      as maternal obesity, multiparity, previous gestational diabetes and previous
      delivery of an infant weighing 4000 g or more, only the latter was associated
      with fetal overgrowth with a risk level 4.7 higher than the control group. Group
      1 patients had a significantly higher incidence of pregnancy-induced hypertension
      and preterm birth. There were no differences in the frequency of 5-min Apgar
      score < 7 and metabolic complications among the infants of all groups. We found a
      significantly higher rate of shoulder dystocia in Group 1 infants than in infants
      in the other groups. CONCLUSIONS: Our results suggest that a positive GCT at 26
      30 weeks is the most important risk factor for fetal overgrowth. This result was
      strongly enforced in patients who had also shown a positive early GCT at 16-20
      weeks.

PMID- 9242199
TI  - Testicular dysfunction in adrenomyeloneuropathy.
AB  - Adrenomyeloneuropathy (AMN) is a disorder due to a disturbance in the peroxisomal
      beta-oxidation of saturated very long chain fatty acids. It is characterized by
      symptoms of the nervous as well as the endocrine systems, especially the adrenal
      cortex and the gonads. We investigated the testicular function in 49 male AMN
      patients aged 36.2 +/- 1.5 years (range, 18.5-59 years). Twenty-four of these
      patients were suffering from adrenocortical insufficiency. Twenty-five AMN
      patients showed neurological symptoms without 'Addison's disease'. To register
      the frequency and the degree of gonadal impairment, LH and FSH, testosterone,
      free testosterone and inhibin-B were determined. Gonadotropin concentrations were
      significantly higher in AMN patients than in healthy controls (LH, 8.0 +/- 1.2 vs
      2.77 +/- 0.11 IU/l; FSH, 10.1 +/- 1.6 vs 4.0 +/- 0.17 IU/l; P < 0.001). Serum LH
      was elevated in 31 patients (63.3%); 28 patients (57.1%) showed elevated serum
      FSH indicating deficient spermatogenesis. Mean testosterone did not differ
      significantly between patients and healthy controls, but mean free testosterone
      was significantly lower in patients than in controls (16.3 +/- 1.0 vs 28.5 +/-
      1.68 pg/ml, P < 0.002). Inhibin-B concentrations did not differ between AMN
      patients and healthy men. The testosterone/LH ratio reflecting an impairment of
      the Leydig cells was significantly lower in AMN patients than in controls (P <
      0.01). An impairment of the Leydig cells and/or of the Sertoli cells was evident
      in 81.6% of AMN patients. Twenty-one of thirty-nine patients (53.8%) admitted
      erectile dysfunction. These data indicate that endocrine dysfunction in AMN is
      not only confined to adrenocortical functions, but testicular dysfunctions also
      frequently occur, thus permitting the term 'adreno-testiculo-myelo-neuropathy'.

PMID- 9242200
TI  - Variability of endocrinological dysfunction in 55 patients with X-linked
      adrenoleucodystrophy: clinical, laboratory and genetic findings.
AB  - X-linked adrenoleucodystrophy (ALD) has been shown to be one of the most frequent
      causes of Addison's disease in men. It is characterized by an impaired
      peroxisomal beta-oxidation of very long chain fatty acids and is associated with
      mutations of the ALD gene resulting in a defective peroxisomal membrane transport
      protein. There is a striking variability of endocrinological and neurological
      symptoms in patients with ALD, with no clearly evident correlation between
      mutations of the ALD gene and the different neurological phenotypes. No data on
      endocrinological symptoms and the ALD genotype have been published so far. We
      report endocrinological, clinical, laboratory and molecular genetic data from 55
      patients with ALD from 34 families. Endocrinological symptoms of adrenal
      insufficiency were observed in 33 patients, 20 of whom showed additional
      neurological symptoms of cerebral ALD or adrenomyeloneuropathy. Isolated
      neurological symptoms were seen in 12 patients; in nine patients there were
      neither endocrinological nor neurological symptoms. Mutations of the ALD gene (n
      = 28) were detected in 50 patients (including nine sets of brothers) from 32
      families. No correlation was found between the ALD gene mutation and
      endocrinological dysfunction. However, we found that all sets of brothers were
      concordant for the endocrinological phenotype (cortisol synthesis was reduced in
      two sets and normal in seven sets), whereas four sets showed a discordant
      neurological phenotype. As yet unknown hereditary factors other than mutations
      within the ALD gene may interfere with the endocrinological phenotype more
      strongly than with the neurological phenotype of ALD.

PMID- 9242201
TI  - Melatonin concentration before and during testosterone replacement in primary
      hypogonadic men.
AB  - OBJECTIVE: To study circadian levels of melatonin in primary hypogonadic adult
      men before and after testosterone treatment. DESIGN AND METHODS: Circadian serum
      melatonin profiles were studied in six men with primary hypogonadism before and
      during testosterone substitution and compared with an age-matched control group
      (n = 6). RESULTS: Hypogonadal patients had higher plasma melatonin concentrations
      than the control group during day time (34.2 +/- 8.8 compared with 5.4 +/- 0.5
      ng/l, means +/- SD; P < 0.005) and night-time (74.8 +/- 34.5 compared with 30.8
      +/- 3.2 ng/l). A 3 months course of testosterone replacement treatment in the
      hypogonadal group was followed by a diminution of the amplified melatonin
      circadian rhythm, with lower mean values both during the day (34.2.8 +/- 8
      compared with 12.7 +/- 2.45 ng/l, P < 0.001) and at night (74.8 +/- 34.5 compared
      with 41.5 +/- 13.5 ng/l, P < 0.01), and a decrease in the total area under the
      curve (958 +/- 318 compared with 475.5 +/- 222.9, P = 0.046). There was a
      significant negative correlation between melatonin (r = -0.69) and testosterone
      concentrations. CONCLUSIONS: These data indicate that diminished testosterone in
      male primary hypogonadism is associated with enhanced plasma levels of melatonin,
      and that testosterone substitution treatment induces a deamplification of the
      circadian rhythm of melatonin values in humans.

PMID- 9242202
TI  - Final height of patients treated for isolated GH deficiency: examination of 83
      patients.
AB  - The aim of the present study was to evaluate retrospectively the influence of
      various auxological and laboratory parameters on final height in a group of GH
      deficient children after replacement therapy and to compare their final height
      with that of a group of short children with normal GH secretion and hence not
      treated. The final height was evaluated of 83 patients (51 males and 32 females)
      affected by idiopathic isolated GH deficiency and treated with recombinant human
      GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short
      stature (mean height for chronological age in standard deviation score (SDS) 
      2.21) due to idiopathic isolated GH deficiency (GH peak < 8 micrograms/l after
      two pharmacological tests and/or mean GH concentration < 3.3 micrograms/l during
      the night) and treatment with recombinant hGH for at least 2 years at a dose of
      15-20 U/m2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological
      age at diagnosis was 12.2 +/- 1.7 years; 35 were prepubertal and 48 pubertal. The
      final height of 51 untreated short stature (mean height for chronological age in
      SDS -2.13 at diagnosis) subjects (42 males and 9 females: 29 prepubertal and 22
      pubertal at diagnosis with mean chronological age 11.6 +/- 2.4 years) with normal
      GH secretion was also evaluated. In the treated subjects final height SDS was
      higher than that of the untreated group (-1.3 vs -1.7 SDS; P = 0.01). Both
      treated and untreated subjects showed a final height lower than target height,
      but 39% of the treated subjects vs only 20% of the untreated group (P = 0.035)
      had a final height greater than target height. In the treated subjects this
      percentage was higher in the patients improving their height for bone age in the
      first years of therapy. While treated females showed a positive correlation only
      between target and final height (P = 0.0001), in treated males final height
      correlated with the Bayley-Pinneau prediction at diagnosis, height for
      chronological age and bone age at diagnosis and target height. Patients who
      started therapy before puberty also showed these correlations with data
      calculated at the onset of puberty, together with a correlation with
      chronological age at the onset of puberty. When considering the influence of GH
      response at tests on final height, the percentage of subjects exceeding target
      height increased progressively according to the severity of the GH deficiency.
      There was no difference in height gain between the patients starting therapy
      before or during puberty. The height gain, however modest, obtained by our
      treated patients, the number of patients with final height greater than target
      height and the favourable comparison with the untreated short-stature subjects
      represent a promising result, which could be improved by personalizing treatment.

PMID- 9242203
TI  - Serum leptin in obesity is related to gender and body fat topography but does not
      predict successful weight loss.
AB  - OBJECTIVE: Leptin is the product of the ob gene shown to regulate body fat and
      appetite in mice. It is produced by human adipose tissue also, but its
      physiological functions in man are poorly known. STUDY DESIGN AND METHODS: We
      studied serum leptin concentrations in ten obese men and 35 obese women (age and
      body mass index 42 +/- 7 years and 35.1 +/- 3.6 kg/m2 respectively) before
      (baseline) and at 17 and 57 weeks during weight loss of 10.9% of the initial
      weight. RESULTS: Serum leptin concentrations at baseline were 55% higher in women
      than in men (after adjustment for age and body fat mass, P = 0.002) and remained
      so during the follow-up. At baseline, serum leptin correlated with fat mass (r =
      0.60, P < 0.001) estimated by bioelectrical impedance, and the changes in leptin
      concentrations from baseline to week 17 correlated with the changes in fat mass
      (r = 0.73, P < 0.001), but baseline leptin levels were not predictive of the
      successful weight loss. Leptin concentrations correlated with hip circumference
      (r = 0.49, P < 0.001 at baseline adjusted for age and sex), but the correlation
      with waist circumference became evident only during the weight loss (at week 57,
      r = 0.63, P < 0.001). CONCLUSIONS: Serum leptin concentrations are higher in
      obese women than in obese men before and during weight loss, but the topography
      of fat tissue influences serum leptin concentrations. Serum leptin concentrations
      do not predict the response to weight reduction.

PMID- 9242204
TI  - Leptin levels are strongly correlated with those of GH-binding protein in
      prepubertal children.
AB  - OBJECTIVE: Nutritional status is an important determinant of growth, and previous
      studies have indicated that this is due, at least in part, to an increased target
      tissue sensitivity to GH. An attractive candidate for mediating this effect is
      leptin, a hormone secreted by the adipose tissue. The aim of this study was to
      investigate if there was a connection between GH-binding protein (GHBP) and
      leptin. DESIGN AND METHODS: We investigated the relationship between serum levels
      of leptin and those of GHBP in 229 prepubertal children. These included 107
      healthy children with normal GH secretion, 55 GH-deficient (GHD) children and 55
      children born small for gestational age (SGA) sampled on one occasion for GHBP
      and leptin, and 12 healthy children followed longitudinally at monthly interval
      for 1 year. RESULTS: In the healthy children and in those born SGA, the serum
      concentration of GHBP was positively correlated with that of leptin (r = 0.65, P
      < 0.001; r = 0.74, P < 0.001 respectively). There was no correlation between GHBP
      and leptin in the group of children with GHD (r = 0.27, not significant). This
      means that leptin alone explained 42% of the variation of GHBP in the healthy
      group and 55% in the SGA group. The correlation remained after adjustment for
      body mass index and age in the healthy children (r = 0.57, P < 0.0001, r2 = 0.33)
      and for children born SGA (r = 0.74, P < 0.0001, r2 = 0.55). There was a positive
      correlation between the intra-individual monthly changes in GHBP and changes in
      leptin respectively, in the 12 healthy children followed longitudinally, the mean
      of the correlation coefficients was 0.38 (median = 0.29; range 0.03 to 0.86; P <
      0.05). CONCLUSIONS: There was a highly significant correlation between serum
      levels of leptin and those of GHBP, except in children with GHD. The possibility
      that leptin could mediate the effects of body fat mass on GH sensitivity,
      therefore, merits further investigation.

PMID- 9242205
TI  - Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal
      sinus sampling to diagnose pituitary-dependent Cushing's syndrome.
AB  - Simultaneous bilateral inferior petrosal sinus (IPS) sampling has been repeatedly
      proposed to be a highly specific approach for the diagnosis of Cushing's disease
      and 100% sensitivity in detecting autonomous pituitary ACTH secretion by an
      adenoma has been reported in a large series. We now report on a patient suffering
      from ACTH-dependent Cushing's syndrome in whom repeated bilateral IPS sampling
      failed to detect a central/peripheral gradient diagnostic for autonomous
      pituitary ACTH secretion during initial evaluation. Applying lysine vasopressin
      as the corticotroph secretatogue, the maximum central/peripheral gradient was 1.0
      before and 1.1 following stimulation. Moreover, results of high dose
      dexamethasone and corticotrophin releasing hormone administration suggested
      ectopic ACTH secretion. Since thorough diagnostic procedures failed to localise a
      suspected carcinoid tumour, occult ectopic Cushing's syndrome was diagnosed.
      Eight years later, a pituitary macroadenoma was detected by magnetic resonance
      imaging (MRI), IPS catheterisation then revealed a maximal central/ peripheral
      gradient of 9.3 before and 20.4 after the intravenous administration of lysine
      vasopressin. Resected tumour tissue was classified as a typical densely
      granulated ACTH cell adenoma. We conclude that repeated MRI scans should be
      included in the follow-up of patients with a diagnosis of occult ectopic
      Cushing's syndrome to avoid the risk of overlooking 'occult eutopic Cushing's
      syndrome'.

PMID- 9242206
TI  - Use of In-111 pentetreotide scintigraphy in the diagnosis of a midgut carcinoid
      causing Cushing's syndrome.
AB  - A 57-year-old man presented with clinical features of hypercortisolism and was
      diagnosed with ACTH-dependent Cushing's syndrome. Biochemical testing showed
      partial suppression of urinary free cortisol with high dose dexamethasone.
      Initial computed tomography (CT) of the chest and abdomen, and magnetic resonance
      imaging of the pituitary were negative. In-111 pentetreotide scintigraphy with
      single photon emission computerized tomography revealed two 'hot' lesions in the
      abdomen which were then confirmed by subsequent directed thin-slice abdominal CT
      and small bowel barium study. At surgery, two segments of ileum, adjoining
      mesentery and lymph nodes were resected. Histopathology was consistent with a
      malignant carcinoid tumor of the ileum which stained intensely for ACTH. Plasma
      ACTH, and serum and urinary cortisol normalized postoperatively. To our
      knowledge, this is the first reported case of ileal carcinoid tumor causing
      Cushing's syndrome with premortem diagnosis. Another unique feature of this case
      is that In-111 pentetreotide scan provided the decisive clue to localization of
      the tumor.

PMID- 9242207
TI  - Atrial natriuretic hormone responses to clonidine in patients with panic disorder
      and in healthy control subjects.

PMID- 9242208
TI  - Amiodarone induces a different pattern of ultrastructural change in the thyroid
      to iodine excess alone in both the BB/W rat and the Wistar rat.
AB  - Amiodarone (AMD)-induced toxicity can be a life-threatening complication which
      limits the use of amiodarone as an anti-arrhythmic agent. The aim of the present
      study was to determine the nature of AMD toxicity by comparing ultrastructural
      changes induced by AMD and equivalent amounts of iodide in two animal models, the
      Wistar and the autoimmune BB/W rat. Rats were divided into control (water), AMD-
      (30 mg AMD/kg) or iodide-treated (10 mg/kg) groups. Thyroids were removed at 15
      weeks and processed for electron microscopy. We found that AMD induced specific
      ultrastructural changes of thyroid cytotoxicity in both rat models, which were
      distinct compared with changes induced by excess iodide alone. Specific changes
      included marked distortion of thyroid architecture, evidence of necrosis and
      apoptosis, inclusion bodies, lipofuscinogenesis and markedly dilated endoplasmic
      reticulum (ER). Our data indicate that AMD is directly cytotoxic to the thyroid
      an effect mediated by disruption of subcellular organelle function. ER dilatation
      is suggestive that AMD cytotoxicity may be mediated through disruption of the
      protein sorting pathways leading to a drug-induced form of ER storage disease.
      The predilection of the thyroid to AMD may be explained by the additive effects
      of excess iodine and AMD drug toxicity on protein sorting pathways.

PMID- 9242209
TI  - Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the
      control of prolactin secretion in prepubertal male rats.
AB  - The role of N-methyl-D-aspartate (NMDA) in the control of prolactin (PRL)
      secretion was analysed in prepubertal male rats. In experiment 1, males of
      different ages were decapitated after administration of NMDA or vehicle. In
      experiment 2, 30-day-old males were killed at different times after
      administration of vehicle, NMDA, MK-801 (a non-competitive NMDA antagonist) or
      NMDA plus MK-801. In experiment 3, 23-day-old males were sham-orchidectomized or
      orchidectomized. Orchidectomized males were or were not implanted with Silastic
      capsules containing different amounts of testosterone. On day 30, the animals
      were decapitated after administration of vehicle, NMDA or MK-801. In experiment
      4, 30-day-old male rats were decapitated after being injected with vehicle, NMDA,
      Nw-nitro-L-arginine methyl ester (NAME) (an inhibitor of nitric oxide (NO)
      synthase), or NMDA plus NAME. Serum PRL concentrations, and dopamine pituitary
      and hypothalamic content were measured. In experiment 5, males pretreated with
      vehicle or NAME were killed after administration of the precursor of serotonin
      synthesis 5-hydroxytryptophan (5-HTP), the 5-HT1 receptor agonist 8-hydroxy-2-(di
      n-propylamino) tetralin (8-OH-DPAT) or the 5-HT2 agonist (+/-) 2,5-dimethoxy-4
      iodoamphetamine hydrochloride (DOI). Finally, the effects of NMDA, NAME and
      sodium nitroprusside (SNP) were tested in dispersed adenohypophyseal cells. We
      found that: (1) antagonism of NMDA receptors with MK-801 decreased PRL secretion
      in intact, orchidectomized and orchidectomized-testosterone treated male rats;
      (ii) NMDA inhibited PRL release in vivo through an increase in dopamine release
      and this effect was potentiated by NAME and prevented by testosterone; (iii) NMDA
      inhibited PRL, secretion in vitro and this effect was observed in presence of
      both SNP and NAME; (iv) NAME blocked the stimulatory effects of 5-HTP and DOI on
      PRL secretion. We conclude that endogenous glutamate stimulates PRL release and
      that NO might have a pivotal role in the mechanisms involved in the control of
      PRL release, inhibiting the release of dopamine and modulating the effects of
      NMDA and 5-HT.

PMID- 9242210
TI  - Translocation 1;19 in two brain tumors.
AB  - We report two-cases of brain tumors, one childhood medulloblastoma and one adult
      glioblastoma with an unusual chromosomal abnormality: a t(1;19)(q23;q13). We
      analyzed these karyotypes using fluorescence in situ hybridization (FISH) and
      wonder if this chromosomal aberration could represent a particular entity in
      these brain tumors like t(1;19) in ALL.

PMID- 9242211
TI  - Cytogenetic analysis of adamantinoma of long bones: further indications for a
      common histogenesis with osteofibrous dysplasia.
AB  - Five adamantinomas of long bones were cytogenetically characterized to
      investigate the role of chromosomal aberrations in their histogenesis, as well as
      a putative relationship between adamantinoma and osteofibrous dysplasia (OFD).
      Three tumors had a classic histologic subtype, with abundant epithelium. Two of
      them revealed trisomies 7, 8, 12, and 19, combined with a balanced translocation,
      t(10;12), with centromere breakpoints in one tumor. The third showed a karyotype
      51,XY, +X, +7, +12, +19, +21. The fourth tumor, of OFD-like subtype, showed
      trisomies 7, 8, and a small marker chromosome in a low percentage of cells. The
      fifth tumor, also of OFD-like subtype, displayed only a few keratin-positive
      cells from the multiple tissue blocks investigated. This latter tumor revealed a
      clonal abnormality with a karyotype 46,XX,t(2;11)(p23;q14)inv(11)(p14q14), which
      was confirmed with fluorescence in situ hybridization (FISH), using chromosome
      specific library probes and chromosome 11 locus-specific probes. The trisomies 7,
      8, and 12 also were described in OFD, which suggests a common histogenesis of OFD
      and adamantinoma. Our findings further support the probability of clonal origin
      of OFD. The OFD-like component may be an integral element of adamantinoma, rather
      than a tissue reaction to epithelial tumor cells.

PMID- 9242212
TI  - Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in
      Ewing tumors.
AB  - The t(11;22)(q24;q12) translocation is found in about 85% of Ewing tumors and
      leads in all cases to an EWS/FLI1 fusion gene. In a few instances, complex
      translocations, involving chromosomes 11, 22 and a third chromosome or other
      variant translocations not involving chromosome 11 also have been reported. These
      rearrangements generate an active fusion gene between the EWS gene and either the
      human FLI1 gene or other members of the ETS gene family: the ERG gene localized
      in band 21q22.2, the ETV1 gene localized in band 7p22, or the E1AF gene localized
      in band 17q12. Using fluorescence in situ hybridization (FISH) on interphase
      nuclei or metaphases, we report here the characterization of particular
      karyotypes in Ewing tumors, namely a complex t(2;11;22) translocation, a variant
      t(12;22) translocation, and one Ewing tumor without specific rearrangements but
      with an EWS/ERG fusion gene demonstrated by molecular analysis. These molecular
      cytogenetic methods allowed us (1) to precisely localize the genomic breakpoints
      within-EWSR1 and EWSR2 and to identify the chromosome carrying the fusion gene;
      (2) to determine the nature of events generating the fusion genes; (3) to
      demonstrate that some variant translocations represent masked complex
      translocations; and (4) to show that the generation of an EWS/ERG fusion gene
      cannot be obtained through a simple balanced translocation.

PMID- 9242213
TI  - Partial duplication of the MLL gene in acute myelogenous leukemia without
      karyotypic aberration.
AB  - Partial duplication of the MLL gene is a recently characterized novel genetic
      mechanism for leukemogenesis. A close association with trisomy 11 has been
      observed. A case of acute myelogenous leukemia (AML) M6 without karyotypic
      abnormality was found to have rearrangement of the MLL gene. Southern analysis
      with an MLL exon 2 probe revealed partial duplication of the MLL gene, with a
      duplicated MLL transcript amplified by reverse transcription polymerase chain
      reaction (RT = PCR). The presence of trisomy 11 was excluded by fluorescence in
      situ hybridization (FISH). Few cases of AML with MLL gene duplication have been
      reported, and they showed involvement of the M1, M2, and M4 subtypes. This case
      is the first reported case with an M6 phenotype, and highlights the importance of
      investigating for MLL gene mutations in all subtypes of AML, as they may carry
      prognostic significance.

PMID- 9242214
TI  - Chromosome arm 17p deletion analysis reveals molecular genetic heterogeneity in
      supratentorial and infratentorial primitive neuroectodermal tumors of the central
      nervous system.
AB  - The current World Health Organization (WHO) classification groups together both
      infratentorial neoplasms (medulloblastomas) and their supratentorial counterparts
      as primitive neuroectodermal tumors (PNETs), implying a common origin. Previous
      analyses of medulloblastoma have shown loss of chromosome arm 17p as the most
      frequent genetic abnormality: the molecular genetic constitution of
      supratentorial PNETS has not been systematically studied. We therefore examined 8
      hemispheric PNETs and 35 medulloblastomas with 17p restriction fragment length
      polymorphism (RFLP) and microsatellite markers. We also examined the TP53 tumor
      suppressor gene by a combined polymerase chain reaction-denaturing gradient gel
      (PCR-DGGE) technique. Our results showed that all of the 17p markers tested were
      preserved in all of the supratentorial PNET specimens. In contrast, loss of
      distal chromosome arm 17p was detected in 37% of the medulloblastomas. Analysis
      of the TP53 gene showed 2 mutations in the medulloblastomas and no mutations in
      the supratentorial tumors. These results show that the most common molecular
      genetic abnormality in infratentorial PNETS is absent in their supratentorial
      counterparts and suggests that alternative pathways and genetic events may be
      involved in their etiology.

PMID- 9242215
TI  - Acute myeloblastic leukemia associated with trisomy 8 and translocation 8;21 in a
      child with Down syndrome.
AB  - The present study examined an 11-year-old girl with Down syndrome who suffered
      from acute myeloblastic leukemia (AML) preceded by preleukemic pancytopenia.
      Chromosomal analysis of leukemic cells revealed a chromosome change at t(8;21)
      and trisomy 8 associated with constitutional trisomy 21. Treatment with
      antineoplastic agents led to complete remission.

PMID- 9242216
TI  - Comparison of DNA flow cytometry and fluorescence in situ hybridization with a
      set of 10 chromosome-specific DNA probes in four head and neck carcinomas.
AB  - Four squamous cell carcinomas of the oral cavity were simultaneously analysed by
      DNA flow cytometry (FCM) and fluorescence in situ hybridization (FISH) with alpha
      telomeric DNA probes specific for chromosomes 1, 2, 3, 6, 7, 8, 10, 12, 17, and
      X. Nuclei with 2 hybridization signals for most chromosomes were in agreement
      with flow cytometric DNA content in a diploid tumor, but a monosomy 8 for half of
      the cells indicated a tumor clone with an aberrant chromosome 8. Aberrations of
      virtually all chromosomes were found in 3 aneuploid tumors. Comparing the
      relative numbers of disomal and aneusomal nuclei with the corresponding
      proportions of DNA diploid and aneuploid sample cells provided evidence that the
      flow cytometrically diploid cell population of an aneuploid tumor consisted of
      both karyotypically normal and abnormal cells. Although there was a high degree
      of concordance between aberrant DNA content and magnitude of chromosomal
      aberration, discrepancies between both methods suggested a notable clonal
      heterogeneity in aneuploid tumor cell populations. These results demonstrate that
      a simultaneous application of DNA flow cytometry contributes to broaden the
      utility of interphase cytogenetics.

PMID- 9242217
TI  - Cytogenetic analysis of 120 primary pediatric brain tumors and literature review.
AB  - We report chromosome results from 108 pediatric central nervous system (CNS)
      tumors. From our data and those in the literature we found that (1) cerebellar
      and low-grade astrocytic tumors, including gangliogliomas, are most often
      karyotypically normal; (2) supratentorial tumors were more frequently high-grade
      tumors that demonstrated a complex karyotype. Chromosome abnormalities were
      similar to those described in adult astrocytic tumors, namely, +7, 9p
      abnormalities, and -10; (3) primitive neuroectodermal tumors (PNETs) were
      virtually always karyotypically abnormal with a high frequency of +7, -8, i(17q),
      and -22. PNETs with -22 may represent a subset of tumors; (4) typical choroid
      plexus papillomas showed a normal karyotype, atypical papillomas showed a
      hyperdiploid karyotype (with +7, +12, and +20), choroid plexus carcinomas showed
      a hyperhaploid karyotype; (5) a few ependymomas showed hyperdiploidy or
      hypertetraploidy; (6) germ cell tumors showed complicated karyotypes; (7)
      monosomy 22 or 22q abnormalities appear to be a recurring finding in the
      malignant rhabdoid tumors; and (8) meningiomas showed -22 or 22q abnormalities
      associated with a complex karyotype. In general, in pediatric CNS tumors the
      least differentiated neoplasms have the greatest number of cytogenetic
      abnormalities. However, our present morphologic criteria for tumor diagnosis do
      not always correlate with a consistent karyotype, and further study of pediatric
      brain tumor morphology, site, behavior, and karyotype is required.

PMID- 9242218
TI  - Allelic imbalance at chromosome 1q21 in Wilms tumor.
AB  - The Wilms tumor suppressor gene 1, WT1, located on chromosome 11p13 is mutated in
      only a subset of Wilms tumors. Cytogenetic studies of Wilms tumors show that the
      most frequent structural anomalies after those affecting chromosome 11p are
      rearrangements of 1q, suggesting that there is a gene involved in Wilms tumor
      etiology in this region. The WT1 target sequence +P5 (D1S3309E), isolated using
      whole-genome polymerase chain reaction (PCR), binds all WT1 isoforms in vitro and
      has been mapped to 1q21-22. As +P5 may mark a 1q Wilms tumor gene, constitutional
      and tumor DNA from 33 Wilms tumor patients (36 tumors) was screened for allele
      imbalance using microsatellite markers from 1p21 to 1q44. Although no gross
      rearrangements of the +P5 region were found, this study demonstrates allele
      imbalance for 1q in 12% of patients (5/36 tumors), defining a smallest region of
      overlap at 1q21. This finding supports a role for 1q21 in Wilms tumorigenesis.

PMID- 9242219
TI  - Clonal chromosome aberrations with monosomy of chromosome 8 in a case of grade
      III chondrosarcoma.
AB  - We report cytogenetic findings in a case of grade III chondrosarcoma. Complex
      clonal chromosome aberrations including monosomy of chromosomes 4, 8, 13, and a
      consistent t(5;14)(q23;p12) were observed in all cells. There were no structural
      or numerical anomalies involving chromosome 12. The complexity of the chromosome
      aberrations reflect the advanced stage of this chondrosarcoma; we suggest a
      possible involvement of the EXT1 gene located on chromosome 8.

PMID- 9242220
TI  - Allele loss in colorectal cancer at the Cowden disease/juvenile polyposis locus
      on 10q.
AB  - The genes that are mutated in inherited cancer syndromes are often involved in
      the pathogenesis of sporadic cancers of the types that characterize those
      syndromes. In colorectal cancer such loci include the familial adenomatous
      polyposis (APC) gene and the hereditary nonpolyposis colorectal cancer (DNA
      mismatch repair) genes. Juvenile hamartomatous polyposis syndromes, which include
      Juvenile Polyposis and Cowden disease, also predispose to colorectal cancer. The
      gene for Cowden disease has recently been localized to chromosome 10q22-q23, and
      a juvenile polyposis locus, JP1, has been reported as mapping to the same
      location. We have studied up to 70 cases of sporadic colorectal cancer for allele
      loss at markers predominantly on the long arm of chromosome 10, including loci
      flanking the putative Cowden Disease/JP1 locus. Frequencies of allele loss of
      about 35% were found close to this locus, whereas low frequencies of allele loss
      were found elsewhere on 10q. Mutations at the putative Cowden Disease/JP1 locus
      may therefore be important in sporadic colorectal cancer and fine mapping of
      allele loss on 10q in sporadic colon cancers may help to refine the position of
      this gene.

PMID- 9242222
TI  - A case of acute nonlymphocytic leukemia with a derivative chromosome 5 resulting
      from a subtle unbalanced translocation, der(5)t(5;17)(p15.3;q25.1).

PMID- 9242221
TI  - Cytogenetic support for early malignant change in a diffuse neurofibroma not
      associated with neurofibromatosis.
AB  - A 62-year-old woman presented with a solitary diffuse neurofibroma; a second
      recurrence showed features indicative of malignancy, but insufficient for a
      certain histologic diagnosis. Cytogenetic analysis revealed abnormalities
      previously described in malignant peripheral nerve sheath tumors and not in their
      benign counterparts, thus supporting the histologic suspicion of emerging
      malignancy.

PMID- 9242223
TI  - No DNA copy number changes in osteochondromas: a comparative genomic
      hybridization study.
AB  - Cytogenetic changes in osteochondroma samples were studied by comparative genomic
      hybridization and by chromosome banding. No DNA copy number changes (15 patients)
      or chromosomal aberrations (9 patients) were observed in any of the patients.

PMID- 9242224
TI  - Chromosomal translocation, t(1;11)(q12;p15), in an extragonadal immature
      teratoma.
AB  - A case of immature teratoma arising from the base of the skull is reported. The
      cytogenetic analysis revealed t(1;11)(q12;p15) as a sole chromosomal abnormality,
      suggesting that the breakpoint on chromosome 11 plays an important role in the
      early oncogenesis of human germ cell tumors (GCTs).

PMID- 9242225
TI  - Partial trisomy 9 in a patient with polycythemia vera.

PMID- 9242226
TI  - Potential biomarkers of benzene exposure.
AB  - Biological markers or biomarkers of exposure are indicators for the evaluation of
      the internal dose of a xenobiotic. Biomarkers integrate exposure from all routes
      and sources. This review presents a short overview of potential biomarkers of
      benzene exposure currently under investigation, the methodology used for their
      determination, and experimental findings and their usefulness and specificity in
      assessing exposure to benzene. Potential biomarkers of benzene exposure are
      benzene, benzene metabolites, and adducts formed by reactive benzene metabolites
      with cellular constituents. The potential biomarkers of benzene exposure
      described in this review are: (1) benzene, the parent hydrocarbon; (2) ring
      hydroxylated urinary metabolites, phenol, catechol, hydroquinone, and 1,2,4
      trihydroxybenzene; (3) trans,trans-muconic acid, a urinary ring-opened
      metabolite; (4) N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine, a urinary metabolite
      of benzene, phenol, and hydroquinone; (5) S-phenylmercapturic acid, a glutathione
      derived adduct; (6) N7-phenylguanine, a DNA adduct; and (7) S-phenylcysteine and
      N-phenyl-valine, hemoglobin/protein-derived adducts.

PMID- 9242227
TI  - Oxidative defense enzyme activity and mRNA levels in lenses of diabetic rats.
AB  - This study examines the mRNA expression and enzyme activity of oxidative defense
      enzymes during the course of streptozotocin-induced hyperglycemic cataract
      development. Diabetes was produced in 5-wk-old male Sprague-Dawley rats by
      administering streptozotocin ip and mRNA expression and enzyme activity were
      monitored on d 4, 8, 12, 16, 20, 40, 60, and 80; concomitantly, the onset and
      progress of cataract was followed by digital image analysis. Peak enzyme activity
      and mRNA expression were attained between d 20 and 40. Although catalase and
      glutathione peroxidase maintained high levels of mRNA expression through d 60,
      induction of CuZu-superoxide dismutase was transient, with the activity and mRNA
      levels returning to baseline values by d 40. There was a pronounced increase in
      aldose reductase activity, which gradually declined to basal levels by d 60;
      however, the mRNA levels remained unaltered. Other changes included a progressive
      loss of lenticular transparency, which declined to 40% of control by d 80. The
      role of antioxidant defense enzymes and, more interestingly, aldose reductase in
      combating oxidative stress in diabetic cataractogenesis is discussed.

PMID- 9242228
TI  - Oxidation of erythrocyte protein and lipid, and hemolysis in rabbit red blood
      cells treated with benzo[a]pyrene or adriamycin.
AB  - A number of free-radical-generating carcinogens catalyze the oxidative
      modification of macromolecules. Malondialdehyde (MDA), carbonyl content, alanine
      formation, and hemolysis were used as biomarkers of oxidative stress, and were
      determined in rabbit erythrocytes treated in vitro with benzo[a]pyrene or
      adriamycin. MDA and carbonyl content were significantly increased in a
      concentration-dependent manner by carcinogens. Alanine formation was also
      increased in a concentration-dependent manner in rabbit erythrocytes treated with
      carcinogens. Hemolysis occurred in erythrocytes treated with benzo[a]pyrene (540
      microM) or adriamycin (300 microM) between 4 and 8 h of incubation, respectively.
      The hemolysis pattern correlated with increases in MDA, carbonyl content, and
      alanine formation. These data indicate that lipid peroxidation as measured by MDA
      may be the most sensitive indicator for oxidative stress in erythrocytes.
      Hemolysis could thus be applicable to free-radical-induced cellular damage as an
      alternative biomarker of oxidative stress.

PMID- 9242229
TI  - Potentiation of organophosphorus compound-induced delayed neurotoxicity (OPIDN)
      in the central and peripheral nervous system of the adult hen: distribution of
      axonal lesions.
AB  - Clinical manifestations of mild organophosphorus compound-induced delayed
      neurotoxicity (OPIDN) produced by diisopropylphosphorofluoridate (DFP) in adult
      hens are potentiated by posttreatment with phenylmethanesulfonyl fluoride (PMSF).
      The purpose of this study was to assess whether potentiation of mild OPIDN
      produces a pattern of axonal lesions in the central and peripheral nervous system
      similar to that seen in severe OPIDN. Groups of 6 hens each were given the
      following priming/challenge doses sc at 0 and 4 h, respectively: 0.20 ml/kg corn
      oil/0.50 ml/kg glycerol formal (GF) (control); 0.50 mg/kg DFP/GF (low-dose DFP);
      0.50 mg/kg DFP/60 mg/kg PMSF (potentiated DFP); 60 mg/kg PMSF/GF (PMSF alone); 60
      mg/kg PMSF/1.5 mg/kg DFP (protected DFP); and 1.5 mg/kg DFP/GF (high-dose DFP).
      Two hens from each group were used to assay brain neurotoxic esterase (NTE) 24 h
      after the challenge dose, and the remaining hens were scored for deficits in
      walking, standing, and perching ability on d 18. Three hens from each group were
      perfusion-fixed on d 22 and neural tissues were prepared for histologic
      evaluation. DFP and/or PMSF caused > 88% brain NTE inhibition in all treated
      groups, compared to control. Protected DFP yielded no clinical deficits and a
      distribution and frequency of axonal lesions similar to control. PMSF alone
      produced a small increase in the frequency of lesions in the cervical spinal cord
      and peripheral nerves compared to control. Low-dose DFP caused minimal ataxia and
      increased frequency of axonal lesions in dorsal and lateral cervical spinal cord,
      ventral lumbar spinal cord, and inferior cerebellar peduncles (ICP) compared to
      control. Potentiated DFP and high-dose DFP produced maximal ataxia and
      essentially identical increases in the frequency of lesions in dorsal and ventral
      thoracic spinal cord, lateral lumbar spinal cord, and peripheral nerves compared
      to low-dose DFP. The results indicate that PMSF potentiation of mild OPIDN
      induced in adult hens by low-dose DFP results in an overall pattern of axonal
      degeneration like that produced by a threefold higher dose of DFP alone, and
      support the hypothesis that potentiation causes an increase in the frequency of
      axonal lesions in central and peripheral loci normally affected by OPIDN.

PMID- 9242230
TI  - Effects of vanadium upon polyl:C-induced responses in rat lung and alveolar
      macrophages.
AB  - Hosts exposed to vanadium (V) display a subsequent decrease in their resistance
      to infectious microorganisms. Our earlier studies with rats inhaling
      occupationally relevant levels of V (as, ammonium metavanadate, NH4VO3) indicated
      that several nascent/inducible functions of pulmonary macrophages (PAM) were
      reduced. In the present study, V-exposed rats were examined to determine whether
      some of the same effects might also occur in situ. Rats were exposed nose-only to
      air or 2 mg V/m3 (as NH4VO3) for 8 h/d for 4 d, followed, 24 h later, by
      intratracheal (it) instillation of polyinosinic:polycytidilic acid (polyl:C) or
      saline. Analysis of lavaged lung cells/fluids after polyl:C instillation
      indicated that total lavageable cell/neutrophil numbers and protein levels, while
      significantly elevated in both exposure groups (as well as in saline-treated V
      exposed rats), were always greater in V-exposed hosts. Exposure to V also
      affected the inducible production of interleukin 6 (IL-6) and interferon gamma
      (IFN gamma), but apparently not that of tumor necrosis factor-alpha (TNF alpha)
      or IL-1. Although polyl:C induced significant increases in lavage fluid IL-6 and
      IFN gamma levels in both exposure groups, levels were greater in V-exposed rats.
      If calculated with respect to total lavaged protein, however, V-exposed rats
      produced significantly less cytokine. Following polyl:C instillation, there were
      no marked exposure-related differences in basal or stimulated superoxide anion
      production by pooled lavaged cells or PAM specifically. With V-exposed rats,
      pooled cells recovered 24 h after saline instillation displayed reduced
      production (in both cases) compared to the air control cells; PAM-specific
      production was affected only after stimulation. In both exposure groups, polyl:C
      caused decreased superoxide production in recovered cells. Though less apparent
      with pooled cells, there was a time post polyl:C instillation-dependent decrease
      in stimulated PAM-specific superoxide production; this effect was greater in PAM
      from V-exposed rats than in PAM from air controls. Phagocytic activity of PAM
      from rats in both exposure groups was significantly increased by polyl:C
      instillation, although total activity in cells obtained from V-exposed rats was
      always significantly lower compared to air control cells. Our results indicate
      that short-term, repeated inhalation of occupationally relevant levels of V by
      rats modulates pulmonary immunocompetence. Modified cytokine production and PAM
      functionality in response to biological response modifiers (such as
      lipopolysaccharide, IFN gamma, or polyl:C) may be, at least in part, responsible
      for the increases in bronchopulmonary disease in humans occupationally exposed to
      V.

PMID- 9242231
TI  - Effects of glutathione depletion on cadmium-induced metallothionein synthesis,
      cytotoxicity, and proto-oncogene expression in cultured rat myoblasts.
AB  - Cadmium (Cd) is a highly toxic metal and a known carcinogen. Although the
      carcinogenic mechanism of action is unknown, Cd will induce transcriptional
      activation of c-myc and c-jun. We have previously found that the extent of Cd
      induced oncogene expression is limited by the presence of cellular
      metallothionein (MT) in rat L6 myoblasts. Glutathione (GSH) is thought to play an
      important role in protection against Cd before the onset of MT synthesis. Thus,
      this study examined the effects of GSH depletion on Cd-induced MT synthesis,
      cytotoxicity, and proto-oncogene expression in rat L6 myoblasts after
      pretreatment with L-buthionine sulfoximine (BSO), a potent inhibitor of gamma
      glutamyl-cysteine synthetase, which effectively depletes GSH. Exposure of L6
      cells to BSO (5 or 25 microM) resulted in a dose-dependent decrease in cellular
      GSH levels. GSH depletion had no effect on Cd- or zinc-induced MT synthesis.
      Although the depletion of GSH was not itself cytotoxic in L6 cells, BSO
      pretreatment, particularly at the higher dose (25 microM), resulted in a dose
      dependent increase in the sensitivity to Cd cytotoxicity, as assessed by a
      tetrazolium-based dye (MTT) assay. Low levels of Cd (1 microM) slightly increased
      the expression of both c-myc and c-jun as assessed by increases in gene-specific
      mRNA levels, in accordance with previous studies. GSH depletion (5 muM BSO)
      likewise caused an increase in expression of c-myc and c-jun. However, combined
      GSH depletion and Cd exposure decreased levels of c-myc and c-jun transcription
      well below control levels. These results suggest that increased cytotoxicity
      resulting from exposure to Cd after BSO depletion of cellular GSH abrogates the
      oncogene activation observed after either treatment alone. Thus proto-oncogene
      expression induced by Cd appears to be dependent on the absence of over Cd
      induced cytotoxicity.

PMID- 9242232
TI  - Aflatoxins in the lungs of children with kwashiorkor and children with
      miscellaneous diseases in Nigeria.
AB  - Autopsy lung specimens from 20 children with kwashiorkor and 20 with other
      miscellaneous diseases, at the Obafemi Awolowo Teaching Hospital complex, Ile
      Ife, Nigeria, were analyzed for the presence of aflatoxin using high-performance
      liquid chromatography. Aflatoxins were detected in 18 children who died from
      kwashiorkor but only in 13 of those who died from miscellaneous diseases. Of the
      10 children, 5 in each group, who died with pneumonia, all had detectable levels
      of aflatoxins in their lungs. The two children with congestive cardiac failure,
      one secondary to pneumonia and the other secondary to tuberculous pericarditis,
      had more than two detectable aflatoxins in their lungs. These findings
      demonstrate that Nigerian children are exposed to aflatoxins and that high levels
      can accumulate in lung tissue.

PMID- 9242233
TI  - Recent advancements in epilepsy.
AB  - This article reviews selected medical and surgical advances that the authors view
      as important to improving the treatment of patients with epilepsy. This includes
      a review of six new antiepileptic drugs (fosphenytoin, felbamate, gabapentin,
      lamotrigine, toprimimate, and vigabatrin), recent studies of the surgical
      technique of Multiple Subpial Transections, and a summary of a prospective
      longitudinal study on anterior temporal lobectomy.

PMID- 9242234
TI  - Treatment of brain cysticercosis.

PMID- 9242235
TI  - Stereotactic transsylvian, transinsular approach for deep-seated lesions.
AB  - BACKGROUND: Lesions located deep within the frontal and parietal lobes adjacent
      to the internal capsule are often considered surgically inaccessible. We have
      used intraoperative stereotactic lesion localization in conjunction with
      microsurgical dissection of the lateral sylvian fissure to accurately and
      atraumatically approach such lesions through the insular cortex. METHODS: When
      possible, the sylvian fissure is widely opened using standard microsurgical
      technique. However, exploration through a precisely placed exposure no more than
      1.0 cm in length is still feasible. Repeated intraoperative lesion localization
      employing ultrasound, frame-based or frameless stereotaxis was used to guide
      dissection deep to the Insular cortex. RESULTS: Using this approach we have
      resected five cavernous angiomas, three plexiform AVMs and 2 low-grade gliomas.
      There was a single case of transient dysphasia in seven dominant hemisphere
      explorations and a single case of transient somatosensory impairment. Otherwise,
      there were no new transient or permanent postoperative neurologic deficits. In
      two cases, hemiparesis present prior to surgery improved following resection of a
      cavernous angioma. CONCLUSIONS: The transsylvian, transinsular approach can be
      employed to safely expose lesions deep within the cerebral hemisphere. Anatomic
      considerations, surgical technical refinements, and clinical results are the
      subject of this report.

PMID- 9242236
TI  - The course of the prevertebral segment of the vertebral artery: anatomy and
      clinical significance.
AB  - BACKGROUND: The so called "pretransverse or prevertebral segment" of the
      vertebral artery is defined from its origin at the subclavian artery to its entry
      into the respective transverse foramen. In surgery, angiography, and in all
      noninvasive procedures it is of great importance to know the exact details of the
      course and the origin of this segment of the vessel as well as in which
      percentages real abnormalities can be found. METHODS: The VI segment of the
      vertebral artery was investigated both in anatomic preparations and clinical
      studies. A total of 402 vertebral arteries were evaluated (70 anatomic
      preparations in different forms, 181 patients, 95 angiographies of the aortic
      arch, and 86 color coded doppler sonographies). RESULTS: A contorted course was
      found in 157 (39%) cases. The plane of tortuosities demonstrated by the
      respective vessels was found to be horizontal in 40 (44.9%) cases, sagittal in 30
      (33.7%) cases, and frontal in 19 (21.4%) cases. In 51 (32.5%) cases the contorted
      pathway was on the right side, and in 106 (68%) cases, on the left. A hypoplasia
      was found in 16 (10%) cases--11 (4.8%) right and 5 (2.2%) left. We further
      differentiated the convexity lying either medially or laterally in the transverse
      or frontal plane, or oriented dorsally or ventral in the sagittal plane. The
      exact location of the origin of the artery on the circumference of the subclavian
      artery (47% cranial, 44% dorsal, 3% ventral, 6% caudal) and also the average
      values of length and diameter are described. No significant differences between
      tortuous and nontortuous vessels were found with respect to length and diameter.
      A real abnormality of the origin of the vertebral artery was found in 8 (3.5%)
      cases. CONCLUSIONS: The described morphologic variations and frequencies of the
      VI segment of the vertebral artery have clinical applications in a wide field of
      pathologies in that region. To know about these findings seems to be very
      important not only in diagnosis (angiography, color coded doppler sonography) but
      also in their surgical and endovascular treatment.

PMID- 9242237
TI  - Low cerebral blood flow and perfusion reserve induce hyperperfusion after
      surgical revascularization: case reports and analysis of cerebral hemodynamics.
AB  - BACKGROUND: Hyperperfusion syndrome after surgical revascularization is a rare
      complication and there has not been any systematic study on factors that induce
      hyperperfusion after surgery. In this paper, we retrospectively analyzed the
      factors related to this syndrome. PATIENTS AND METHODS: We performed 46 cases of
      surgical revascularization including 33 cases of carotid endarterectomy (CEA) and
      13 cases of superficial temporal artery-middle cerebral artery (STA-MCA)
      anastomosis during the past 5 years. Among these, we encountered three cases of
      hyperperfusion syndrome despite well-controlled blood pressure postoperatively.
      To evaluate factors related to the occurrence of hyperperfusion syndrome, we
      examined four parameters: (1) regional cerebral blood flow (rCBF), (2) the
      increase in the ratio of the postoperative rCBF compared to the preoperative rCBF
      (increase ratio), (3) cerebral perfusion reserve presented by the increase of
      rCBF after acetazolamide administration (delta rCBF), and (4) the difference in
      mean blood pressure between the preoperative and postoperative state (delta BP).
      RESULTS: Preoperative rCBF was significantly lower in cases of hyperperfusion
      syndrome than the control cases (p < 0.01 Mann-Whitney U-test). Moreover delta
      rCBF was evidently lower in the hyperperfusion cases than the control (p < 0.05
      Fisher's exact method). However, there was no significant difference in the delta
      BP between the hyperperfusion cases and the control cases. CONCLUSION: In cases
      of marked low perfusion (low rCBF) with poor perfusion reserve (low delta rCBF),
      hyperperfusion after surgical revascularization can occur even if blood pressure
      is adequately controlled.

PMID- 9242238
TI  - Endoscopic instruments.

PMID- 9242239
TI  - Cranial osteomas: their classification and management. Report on a giant osteoma
      and review of the literature.
AB  - BACKGROUND: Cranial osteomas are regarded by some as very common; yet their
      classification, symptomatology, and management have been neglected. METHODS: We
      report on a giant enostotic convexity osteoma and have reviewed the medical
      literature. RESULTS: A new comprehensive classification for cranial osteomas is
      proposed: (1) intraparenchymal, (2) dural, (3) skull base, and (4) skull vault.
      The latter is in turn, subdivided into exostotic and enostotic variants. Three
      symptom producing enostotic convexity osteomas have been reported in the world
      literature. We also describe a giant enostotic skull vault osteoma and propose an
      original surgical technique used to successfully resect this unusual tumor.
      CONCLUSIONS: Most cranial osteomas are asymptomatic and need not be resected.
      Those that are symptomatic should be managed properly. Their excision, if nor
      properly performed, may lead to unforeseen cerebral complications.

PMID- 9242240
TI  - Chondromyxoid fibroma of the temporal bone.
AB  - BACKGROUND: Chondromyxoid fibromas are benign neoplasms comprising approximately
      0.5% of primary bone tumors. The occurrence of this tumor in the skull is
      extremely rare, with only four previously reported cases involving the temporal
      bone and a total of 17 cases with intracranial involvement. CASE DESCRIPTION: We
      describe the case of a 22-year-old man who experienced a 1-year history of
      headaches with progressive ear pain and mild hearing loss. Computed tomography
      and magnetic resonance imaging of the head demonstrated an extraaxial tumor
      arising from the left temporal mastoid region. A craniotomy was performed and the
      tumor resection required extensive drilling of the temporal bone. Grossly, the
      tumor consisted of a firm semigelatinous myxomatous tissue containing multiple
      areas of calcification and was histologically consistent with chondromyxoid
      fibroma. CONCLUSIONS: Complete resection is the goal of surgery. Recurrence rates
      of 7% to 27% have been reported, dependent on the degree of initial resection.
      Radiation is not recommended because of the potential for sarcomatous conversion.
      Reoperation may be indicated for symptomatic recurrence.

PMID- 9242241
TI  - Surgical removal of a cavernous sinus chondroma.
AB  - BACKGROUND: Chondromas at the base of the skull are most commonly found in the
      parasellar and sellar regions, and present varying degrees of involvement of the
      cavernous sinus. However, those confined mainly to the cavernous sinus are rare,
      and only a few reports show detailed radiological and surgical findings.
      MATERIALS AND METHODS: This 40-year-old woman experienced sudden right orbital
      pain followed by right third and sixth cranial nerve palsies. Computerized
      tomography scan and magnetic resonance image depicted a well-circumscribed mass
      in the right cavernous sinus. A frontotemporal craniotomy with orbito-zygomatic
      osteotomy was used to approach this lesion intradurally. We drilled away the
      anterior clinoid process using a high-speed air drill extradurally, exposed the
      intrapetrous carotid artery, and dissected the right sylvian fissure from the
      distal, fully exposing the surface of the right cavernous sinus. The soft and
      grayish tumor was easily removed using sucker and tumor forceps; the venous
      bleeding from the sinus itself was easily controlled. RESULTS: The tumor was
      successfully removed via a superior triangle. Intradural invasion of the tumor
      and heavy venous bleeding from the sinus were not observed. Histologically, the
      mass was diagnosed as a mature chondroma. The tumor was presumed to originate
      from the right posterior clinoid process. The lesion was totally removed, and
      postoperative right ophthalmoplegia had fully disappeared within 6 months after
      surgery. CONCLUSION: Successful surgical attack of lesions in the cavernous sinus
      requires comprehensive and precise knowledge of the microsurgical anatomy and
      neuroradiology.

PMID- 9242242
TI  - Cavernoma of the cavernous sinus: case report.
AB  - BACKGROUND: The authors report a case of extra-axial cerebral cavernoma localized
      at the level of the cavernous sinus. This pathology is extremely rare, therefore,
      differential diagnosis with tumors such as meningioma is often difficult. During
      recent years, surgical indications for these lesions, congenital and rarely
      hereditary, have become more definite due to the considerable progress made in
      neuroradiologic and microsurgic techniques as well as better anatomic knowledge
      of this region. METHODS: This 49-year-old man was admitted with a 1-year history
      of diplopia. Cranial computed tomography (CT) scan with contrast medium,
      performed prior to admission, showed an expansive lesion at the level of the
      right cavernous sinus. Preoperative neuroradiologic diagnosis, after cerebral
      magnetic resonance imaging (MRI) with gadolinium enhancement and cerebral
      panangiography, was probable cavernoma. The lesion was totally removed via a
      fronto-orbito-temporo-zygomatic craniotomy. RESULTS: Postoperatively, the patient
      had a right oculomotor nerve palsy. This spontaneously resolved 8 months after
      surgery; diplopia also completely disappeared. Early postoperative control MRI
      scans with gadolinium on the 2nd postoperative day and 3 months after operation
      confirmed total removal of the lesion. CONCLUSIONS: The clinical onset and
      neuroradiologic aspect of these lesions and the fact that they rarely involve the
      cavernous sinus, may sometimes make preoperative diagnosis of cavernous sinus
      cavernoma difficult. Nevertheless, given the routine use of microsurgical
      techniques and improved anatomic knowledge of this delicate region, the treatment
      of choice is surgery. However, when doubts exist regarding achievement of total
      removal, radiosurgery is still a valid therapeutic tool.

PMID- 9242243
TI  - Revascularization of the anterior cerebral artery using a free superficial
      temporal artery graft: a case report.
AB  - BACKGROUND: Various bypass procedures have been used to treat occlusive
      cerebrovascular diseases. Most procedures were performed to prevent further
      ischemia in the territory of the middle cerebral artery, while only a few of the
      papers discuss the anterior cerebral artery (ACA) territory. METHOD AND RESULTS:
      A patient who initially presented with several episodes of transient monoparesis
      in the left leg was found to have severe stenosis of the right A2-A3 junction. A
      free superficial temporal artery (STA) graft was anastomosed between the right A2
      and A3 portion intracranially. Transient ischemic attacks immediately disappeared
      after surgery and subsequent cerebral angiography revealed good anterograde
      filling from the A2 to A3 portion via the free STA graft. CONCLUSION:
      Revascularization using a free STA graft is useful for reconstruction of a local
      stenotic lesion, especially in the ACA territory.

PMID- 9242244
TI  - The accessory anterior cerebral artery: case report and anatomic analysis of
      vascular anomaly.
AB  - BACKGROUND: The term "accessory artery" was formulated to describe one of the
      developmental anomalies of the middle cerebral artery. This anomaly consisted of
      the incidence of a vessel that branched off close to the anterior communicating
      artery and supplied a part of the cortex in the region of the middle cerebral
      artery vascularization. METHODS: A panangiography of the cerebral vessels was
      carried out, using the subtraction method, on a woman who suffered from
      subarachnoid hemorrhage. An aneurysm of the anterior communicating artery and
      developmental anomaly of the right anterior cerebral artery were found. During
      the aneurysm operation, the existence of the developmental anomaly was confirmed.
      It was revealed also during a control angiography. RESULTS: An atypical branch of
      the right internal carotid artery was found branching off from section C2, and
      passing below the right optic nerve and the anterior communicating artery. This
      branch ended with a division into the orbitofrontal and frontopolar artery.
      CONCLUSIONS: The atypical branch of the internal carotid artery that partly
      performs the function of the existing proper right anterior cerebral artery, has
      been defined as the accessory anterior cerebral artery.

PMID- 9242245
TI  - Intracerebral capillary telangiectasia and venous malformation: a rare
      association.
AB  - BACKGROUND: The vascular malformations of the brain have been classified into
      arteriovenous, venous, cavernous, and capillary malformations as four discrete
      entities. Various combinations of two discrete malformations in one lesion have
      been reported, some of which can be considered as established associations, while
      others appear to be very rare. Mixed vascular malformations evoke reflections on
      possible interrelations in the pathogenesis of the discrete components. CASE
      DESCRIPTIONS: We report a case of intracerebral capillary telangiectasia
      associated with a venous malformation in a supratentorial paraventricular
      location in a 45-year-old woman with a history of headache. The capillary
      telangiectasia was diagnosed by stereotactic biopsy. Magnetic resonance imaging
      (MRI) and magnetic resonance angiography (MRA) strongly suggested the presence of
      a venous malformation by demonstrating a transcerebral draining vein running
      through the center of the capillary telangiectasia. The association of capillary
      telangiectasia and venous malformation has been reported only twice before and
      exclusively in the posterior fossa, as opposed to the more frequent, established
      associations of capillary telangiectasia and cavernous malformation, and venous
      malformation and cavernous malformation, respectively. CONCLUSIONS: Against the
      background of the established associations, this rare observation possibly places
      capillary telangiectasias, cavernous malformations, and venous malformations
      within the spectrum of a single disease. The common pathogenetic role of a focal
      venous outflow obstruction is discussed.

PMID- 9242246
TI  - Growing fracture of the orbital roof.
AB  - BACKGROUND: Growing fractures rarely arise in the skull base, and their
      pathogenesis and treatment are still debated. METHODS: The clinical and
      radiologic findings of a growing fracture involving the orbital roof in a 5-year
      old boy are presented and the relevant literature is reviewed. RESULTS: The
      clinical picture of growing fracture of the orbital roof is dominated by ocular
      symptoms such as diplopia, eyelid swelling, and displaced eye globe. Computed
      tomography scan is excellent for demonstrating the bony defect in the orbital
      roof while magnetic resonance imaging is more sensitive in showing the
      intraorbital extension of the leptomeningeal cyst. Frontobasal brain injury seems
      to play an important role in the pathogenesis of the fracture growth. Craniotomy
      with direct repair of the dural and bone defects is the treatment of choice.
      CONCLUSION: Growing fracture of the orbital roof may complicate minor head injury
      and should be considered in the differentiated diagnosis in cases of persistent
      ocular symptoms.

PMID- 9242247
TI  - Traumatic spinal subarachnoid hematoma: report of a case with MRI.
AB  - BACKGROUND: Spinal subarachnoid hematoma (SAH) is uncommon following traumatic
      injury to the spine. There are few case reports of neurologic deficit secondary
      to traumatic spinal SAH. CASE DESCRIPTION: This 6-year-old boy was injured in a
      vehicular accident from which he became paraplegic and presented to us 1 week
      later. Plain X rays were normal and a myelo-computed tomography (CT) scan
      demonstrated an irregular intradural lesion from D10-L2. The magnetic resonance
      imaging (MRI) revealed an SAH at D11-12 level, posterior to the cord, which was
      surgically evacuated. The patient did not improve neurologically. CONCLUSION:
      Significant cord injury and neurologic deficit can occur without obvious
      abnormalities on plain X rays or CT scan. MRI is very useful in detecting these
      lesions and can help in their management.

PMID- 9242248
TI  - Rapid resolution of symptomatic acute subdural hematoma: case report.
AB  - BACKGROUND: Only a few cases showing spontaneous resolution of acute subdural
      hematoma (ASDH) have been reported. Several possible mechanisms of spontaneous
      resolution of ASDH have been reported. Two possible hypotheses have been
      suggested: (1) the hematoma is diluted by cerebrospinal fluid (CSF) due to
      tearing of the arachnoid membrane and is washed out, (2) the hematoma is
      compressed by the pressure produced by acute brain swelling and redistributed. In
      this article, we report a patient with a rapid spontaneous resolution of an ASDH
      and discuss the mechanisms. METHODS: We experienced a case of a spontaneous
      resolution of symptomatic ASDH within only 3 hours. Characteristic serial changes
      on computed tomography (CT) corresponding to neurologic changes were obtained.
      RESULTS: Serial CT findings showing changes corresponding to neurologic
      fluctuation were obtained. The characteristic features of the CT findings are as
      follows: (1) participation of CSF at the lateral portion of the hematoma was
      recognized during the early period after injury, (2) no cerebral contusion was
      identified, (3) acute cerebral swelling was not identified, (4) when the
      neurologic state deteriorated, the hematoma had not enlarged, but there was an
      increase in the low-density area corresponding to participation of the CSF and
      midline shift was recognized. CONCLUSION: Spontaneous resolution of ASDH depends
      on both dilution due to CSF participation and redistribution of the blood; but
      acute cerebral swelling is not a necessary condition. Elasticity of the brain and
      absence of cerebral contusion obstructing the outflow of the cerebrospinal fluid
      is optimal.

PMID- 9242249
TI  - Concerning a malpractice case.

PMID- 9242250
TI  - Spinal cord swelling and brain lesions in lupus myelitis.

PMID- 9242251
TI  - The condition of neurosurgery in Argentina: a warning to the rest of us.

PMID- 9242252
TI  - Neurosurgery and worldwide economics.

PMID- 9242253
TI  - Arterial subdural hematoma.

PMID- 9242254
TI  - Glucocorticoid receptor activation lowers the threshold for NMDA-receptor
      dependent homosynaptic long-term depression in the hippocampus through activation
      of voltage-dependent calcium channels.
AB  - The effects of the glucocorticoid receptor agonist RU-28362 on homosynaptic long
      term depression (LTD) were examined in hippocampal slices obtained from adrenal
      intact adult male rats. Field excitatory postsynaptic potentials were evoked by
      stimulation of the Schaffer collateral/commissural pathway and recorded in
      stratum radiatum of area CA1. Low-frequency stimulation (LFS) was delivered at
      LTD threshold (2 bouts of 600 pulses, 1 Hz, at baseline stimulation intensity).
      LFS of the Schaffer collaterals did not produce significant homosynaptic LTD in
      control slices. However, identical conditioning in the presence of the
      glucocorticoid receptor agonist RU-28362 (10 microM) produced a robust LTD, which
      was blocked by the selective glucocorticoid antagonist RU-38486. The LTD induced
      by glucocorticoid receptor activation was dependent on N-methyl-D-aspartate
      (NMDA) receptor activity, because the specific NMDA receptor antagonist D(-)-2
      amino-5-phosphonopentanoic acid (D-AP5) blocked the facilitation. However, the
      facilitation of LTD was not due to a potentiation of the isolated NMDA receptor
      potential by RU-28362. The facilitation of LTD by RU-28362 was also blocked by
      coincubation of the L-type voltage-dependent calcium channel (VDCC) antagonist
      nimodipine. Selective activation of the L-type VDCCs by the agonist Bay K 8644
      also facilitated LTD induction. Both nimodipine and D-AP5 were effective in
      blocking the facilitation of LTD by Bay K 8644. These results indicate that L
      type VDCCs can contribute to NMDA-receptor-dependent LTD induction.

PMID- 9242255
TI  - Calcium dynamics in thorny excrescences of CA3 pyramidal neurons.
AB  - Confocal laser scanning microscopy was used to visualize Ca2+ transients in a
      particular type of dendritic spine, known as a thorny excrescence, in hippocampal
      CA3 pyramidal neurons. These large excrescences or thorns, which serve as the
      postsynaptic target for the mossy-fiber synaptic inputs, were identified on the
      basis of their location, frequency, and size. Whole cell recordings were made
      from superficial CA3 pyramidal neurons in thick hippocampal slices with the use
      of infrared video microscopy; cells with proximal apical dendrites close to the
      surface of the slice were selected. Changes in intracellular Ca2+ levels were
      monitored by imaging changes in fluorescence of the dyes Calcium Green-1 and Fluo
      3. Dual-emission fluorescence imaging was also employed with the use of a
      combination of Fluo-3 and the Ca2+-insensitive dye seminaphthorhodafluor-1. This
      method was used to decrease the potential influence of background fluorescence on
      the calculated changes in intracellular Ca2+ concentration ([Ca2+]i). Somatic
      depolarization produced increases in [Ca2+]i in both the thorn and the
      immediately adjacent dendrite. Changes in [Ca2+]i were time locked with the onset
      of depolarization and the decay began immediately after the termination of
      depolarization. The peak increase in the Ca2+ signal was significantly greater in
      the thorns than in the adjacent dendritic shafts. With the use of high-temporal
      resolution methods (line scans), differences were also seen in the time course of
      Ca2+ signals in these two regions. The decay time constants of the Ca2+ signal
      were faster in thorns than in the adjacent dendritic shafts. These observations
      suggest that voltage-gated Ca2+ channels are localized directly on the dendritic
      spines receiving mossy-fiber input. Furthermore, Ca2+ homeostasis within thorny
      excrescences is distinct from Ca2+ regulation in the dendritic shaft, at least
      over brief time periods, a finding that could have important implications for
      synaptic plasticity and signaling.

PMID- 9242256
TI  - Low-frequency depression of the monosynaptic reflex is not altered by
      tetrodotoxin-induced nerve conduction blockade.
AB  - The present study is part of ongoing investigations into activity-related
      synaptic plasticity in the intact animal. In this investigation we sought to
      determine whether the previously reported increase in synaptic efficacy at the Ia
      motoneuron connection following nerve conduction blockade could be attributed to
      changes in circuitry external to the monosynaptic pathway. Specifically, we used
      the phenomena of low-frequency depression of the extracellularly recorded group I
      monosynaptic reflex (MSR) as an indirect measure of presynaptic inhibition.
      Tibial nerve conduction blockade was achieved by superfusion of the sodium
      channel blocker tetrodotoxin (TTX). An osmotic pump delivered the TTX to the
      tibial branch of the sciatic nerve for a period of either 3 or 10 days. Control
      rats were either unoperated or received implants of pumps not containing TTX.
      Data collection consisted of tibial nerve stimulation (0.1-20 Hz) with bilateral
      recordings of the MSR from the L5 ventral roots. The extent of low-frequency
      depression was compared between treated and untreated sides of TTX-treated
      animals and between treated and untreated animals. Results showed that the extent
      of low-frequency depression was unchanged by either 3 or 10 days of complete
      blockade of tibial afferents. On the basis of this finding, it is concluded that
      the previously reported TTX-induced increase in Ia excitatory postsynaptic
      potential amplitude is unlikely to be due to changes in presynaptic inhibitory
      pathways.

PMID- 9242257
TI  - Origin of the apparent asynchronous activity of hippocampal mossy fibers.
AB  - Fiber volleys (FVs) from the stratum lucidum of rat hippocampal area CA3 were
      recorded extracellularly from in vitro slices in the presence of 10 mM kynurenic
      acid. In agreement with previous work, bulk stimulation of the dentate gyrus (DG)
      near the hilar border leads to an asynchronous FV. Transection of the stratum
      lucidum between the DG stimulation site and the CA3 recording site reduced or
      eliminated the early components of the asynchronous FV, indicating that they are
      of mossy fiber (MF) origin. In contrast, moving the stimulating electrode away
      from the hilus toward the hippocampal fissure reduced or eliminated the late
      components of the FV. Subsequently, we found that bulk stimulation on the
      DG/hilar border induces an antidromic population spike in CA3 pyramidal cells.
      Finally, the MFs and associational collaterals have different conduction
      velocities (0.51 and 0.37 m/s, respectively; temperature = 33 degrees C). From
      these data, we conclude that the late components of the asynchronous FV are due
      to antidromic activation of CA3 collaterals that have been shown to be present in
      the DG and hilus. A corollary of these findings is that bulk stimulation on the
      DG/hilar border can lead to at least two different monosynaptic inputs to CA3
      pyramidal cells: the MFs and the antidromically activated associational
      collaterals. We suggest that when MF synaptic responses are being evoked with the
      use of bulk stimulation, stimulating electrodes should be placed in the outer
      molecular layer of the DG to prevent the activation of hilar-projecting
      associational collaterals. This procedure should be added to the previously
      proposed criteria for preventing polysynaptic contamination of the
      intracellularly recorded evoked MF synaptic response.

PMID- 9242259
TI  - Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal
      neurons.
AB  - Cannabinoids and their analogues have been found to inhibit N- and P/Q-type Ca2+
      currents in cell lines and sympathetic neurons transfected with cannabinoid CB1
      receptor. However, the effects of cannabinoids on Ca2+ currents in the CNS are
      largely unexplored. In this study we investigated whether these compounds inhibit
      Ca2+ channels in cultured rat hippocampal neurons. With the use of antibodies
      directed against the amino-terminus of the CB1 receptor, we found that in 5-day
      cultures pyramidally shaped neurons expressed somatic CB1 receptors, whereas in 4
      wk cultures the receptor was predominately located on neurites. In early
      cultures, the cannabimimetic WIN 55,212-2 reversibly inhibited whole cell Ba2+
      current in a concentration-dependent (K(1/2) = 21 nM) and pertussis-toxin
      sensitive fashion. Inhibition was reduced by the CB1 antagonist SR141716. The
      current was unaffected by the nonpsychoactive enantiomer WIN 55,212-3. Maximal
      inhibition by the nonclassical cannabinoid agonist CP 55,940 and by an endogenous
      cannabinoid, anandamide, were similar to that seen with maximal concentrations of
      WIN 55,212-2. The Ba2+ current modulated by cannabinoids was carried by N-type
      (omega-conotoxin-GVIA-sensitive) and P/Q-type (omega-conotoxin-MVIIC-sensitive)
      channels. These results demonstrate cannabinoid-receptor-mediated inhibition of
      distinct Ca2+ channels in central neurons. Because the channels that underlie
      these currents are chiefly located presynaptically, and are required for evoked
      neurotransmitter release, our results suggest a major role for cannabinoids
      (endogenous and exogenous) in the modulation of synaptic transmission at CNS
      synapses.

PMID- 9242258
TI  - Differential effects of NGF and BDNF on axotomy-induced changes in GABA(A)
      receptor-mediated conductance and sodium currents in cutaneous afferent neurons.
AB  - The effects of nerve growth factor (NGF) and brain-derived neurotrophic factor
      (BDNF) on injury-induced changes in the electrophysiological properties of adult
      rat cutaneous afferent dorsal root ganglion (DRG) neurons were examined. Whole
      cell patch-clamp techniques were used to study gamma-aminobutyric acid-A
      (GABA(A))-receptor-mediated conductance, voltage-dependent sodium currents, and
      action potential waveform in cutaneous afferent neurons (35-60 microm diam)
      cultured from control and axotomized animals. Cutaneous afferent neurons were
      identified by retrograde labeling with hydroxy-stilbamidine (Fluoro-gold, a
      fluorescent retrograde axonal tracer); the sciatic nerve was transected 1 wk
      after Fluoro-gold injection and L4/L5 DRG neurons were cultured 2-3 wk after
      axotomy. NGF, BDNF, or Ringer (vehicle) solution was delivered in vivo directly
      to the transected sciatic nerve stump in axotomized rats via an osmotic pump.
      Recordings were obtained from neurons 5-24 h after culture. Axotomized neurons
      from rats treated with vehicle solution displayed a twofold increase in GABA
      induced conductance and a prominent reduction in the proportion of neurons
      expressing action potentials that had inflections on the falling phase. The
      expression of kinetically slow tetrodotoxin (TTX)-resistant sodium current was
      markedly reduced and an increased expression of kinetically fast TTX-sensitive
      current was observed in neurons from vehicle-treated, axotomized rats. Treatment
      with NGF (0.25 microg/microl at 12 microl/day for 14 days) in axotomized animals
      resulted in an increase in the proportion of neurons expressing TTX-resistant,
      slow sodium currents and inflected action potentials, but had no effect on GABA
      induced conductance. Treatment with BDNF (0.5 microg/microl at 12 microl/day for
      14 days) attenuated the axotomy-induced increase in GABA(A)-receptor-mediated
      conductance while minimally affecting action potential waveform. The observed
      neurotrophin effects occurred independently of cell size changes. These findings
      indicate a differential regulation of GABA(A) receptor and sodium channel
      properties in axotomized rat cutaneous afferent neurons by specific neurotrophic
      factors.

PMID- 9242260
TI  - Static and dynamic membrane properties of large-terminal bipolar cells from
      goldfish retina: experimental test of a compartment model.
AB  - Capacitance measurements allow direct studies of exocytosis and endocytosis in
      single synaptic terminals isolated from bipolar neurons of goldfish retina.
      Extending the technique to intact bipolar cells, with their more complex
      morphology, requires information about the cells' electrotonic architecture. To
      this end, we developed a compartment model of bipolar neurons isolated from
      goldfish retina and tested the model experimentally. The isolated cells retained
      morphology similar to that of bipolar neurons in intact goldfish retina. In whole
      cell recordings, current relaxations in response to 10-mV hyperpolarizing voltage
      pulses decayed with a biexponential time course. This suggests that the cells may
      be described by a two-compartment equivalent circuit with compartments
      corresponding to the soma/dendrites (6-10 pF) and synaptic terminal (2-4 pF),
      linked by the axial resistance (30-60 M omega) of the axon. Four lines of
      evidence validate the equivalent circuit. 1) Similar estimates of
      somatic/dendritic and terminal capacitance were obtained whether the patch
      pipette was attached to the soma or to the synaptic terminal. 2) Estimates of the
      capacitance of the two compartments in intact cells were similar to estimates
      from somata and terminals that were isolated by cleavage of the connecting axon.
      3) When current transients were generated from a more complete computer
      simulation of a bipolar neuron, analysis of the simulated transients with the use
      of the simple two-compartment model yielded capacitance estimates similar to
      those used to set up the simulation. 4) In isolated cells, the model gave
      estimates of depolarization-evoked increases in capacitance of the synaptic
      terminal that were quantitatively similar to those measured in terminals that
      were detached from the rest of the cell. Although in previous studies researchers
      have attempted to apply a similar equivalent circuit to more geometrically
      complex cells, morphological correlates of the equivalent-circuit compartments
      have been elusive. Our results demonstrate that in dissociated bipolar cells,
      precise morphological correlates can be assigned to the equivalent-circuit
      compartments. Additionally, the work shows that time-resolved capacitance
      measurements of synaptic transmitter release are possible in intact, isolated
      bipolar neurons and may also be feasible in intact tissue.

PMID- 9242261
TI  - Metabotropic glutamate receptor agonists alter neuronal excitability and Ca2+
      levels via the phospholipase C transduction pathway in cultured Purkinje neurons.
AB  - Selective agonists for metabotropic glutamate receptor (mGluR) subtypes were
      tested on mature, cultured rat cerebellar Purkinje neurons (> or = 21 days in
      vitro) to identify functionally relevant mGluRs expressed by these neurons and to
      investigate the transduction pathways associated with mGluR-mediated changes in
      membrane excitability. Current-clamp recordings (nystatin/perforated-patch
      method) were used to measure the membrane response of Purkinje neurons to brief
      microperfusion pulses (1.5 s) of the group I (mGluR1/mGluR5) agonists (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (300 microM), quisqualate (5 microM), and
      (R,S)-3,5-dihydroxyphenylglycine (50-500 microM). All group I mGluR agonists
      elicited biphasic membrane responses and burst activity in the Purkinje neurons.
      In addition, the group I mGluR agonists produced alterations in the active
      membrane properties of the Purkinje neurons and depressed the OFF response after
      hyperpolarizing current injection. In parallel microscopic Ca2+ imaging
      experiments, application of the group I mGluR agonists to fura-2-loaded cells
      elicited increases in intracellular Ca2+ in both the somatic and dendritic
      regions. The group II (mGluR2/mGluR3) agonist (2S,3S,4S)-alpha
      (carboxycyclopropyl)-glycine (10 microM) and the group III
      (mGluR4/mGluR6/mGluR7/mGluR8) agonists L(+)-2-amino-4-phosphonobutyric acid (1
      mM) and O-phospho-L-serine (200 microM) had no effect on the membrane potential
      or intracellular Ca2+ levels of the Purkinje neurons. The cultured Purkinje
      neurons, but not granule neurons or interneurons, showed immunostaining for
      mGluR1alpha in both the somatic and dendritic regions. All effects of the group I
      mGluR agonists were blocked by (+)-alpha-methyl-4-carboxyphenylglycine (1 mM), an
      mGluR antagonist. Furthermore, the phospholipase C inhibitor 1-[6-((17beta-3
      methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H -pyrrole-2,5-dione (2 microM)
      blocked the group I mGluR agonist-mediated electrophysiological response and
      greatly attenuated the Ca2+ signal elicited by group I mGluR agonists,
      particularly in the dendrites. The inactive analogue 1-[6-((17beta-3-methoxyestra
      1,3,5(10)-trien-17-yl)amino)hexyl]-2, 5-pyrrolidine-dione (2 microM) was
      relatively ineffective against the electrophysiological response and Ca2+ signal.
      These results indicate that functional group I mGluRs (but not group II or III
      mGluRs) can be activated on mature Purkinje neurons in culture and result in
      changes in neuronal excitability and intracellular Ca2+ mediated through
      phospholipase C. These data obtained from a defined neuronal type, the Purkinje
      neuron, confirm biochemical and molecular studies on the transduction mechanisms
      of group I mGluRs and show that this transduction pathway is linked to neuronal
      excitability and intracellular Ca2+ release in the Purkinje neurons.

PMID- 9242262
TI  - Contextual conditioned fear blocks the induction but not the maintenance of
      lateral septal LTP in behaving mice.
AB  - High-frequency stimulation (HFS) of the fimbria induces long-term potentiation
      (LTP) in the lateral septum. This study was aimed at investigating the effect of
      contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice
      as subjects. For the acquisition of contextual fear conditioning, animals were
      placed in a conditioning chamber, where they were subjected to footshocks (FSs,
      0.6 mA); the following day (retention), animals were reexposed to the chamber.
      Animals from the first group received HFS in their home cages before being
      submitted to conditioning; animals from the second group were first submitted to
      conditioning before receiving HFS during reexposure to the conditioning chamber;
      animals from the third group were submitted to the same regimen as those from the
      second group, except that no FS was delivered in the conditioning chamber; and
      animals from the fourth group received FS in the conditioning chamber but were
      maintained in their home cages the day after for LTP induction. Before
      conditioning, animals from the first group, placed in a familiar context (home
      cage), displayed an LTP of the N3 wave of septal field potential. After
      conditioning, reexposure of these animals to the conditioning chamber produced a
      transient decrease in the amplitude of N3 but did not interfere with the duration
      of maintenance of LTP. Conversely, in animals from the second group, when HFS was
      applied during reexposure to the conditioning chamber the induction of LTP was
      totally blocked. However, mice from the two other groups (3rd and 4th) displayed
      normal levels of LTP. Taken together with previous findings, these data suggest
      that contextual conditioned fear may interfere with certain forms of learning via
      blockade of hippocampal-septal LTP.

PMID- 9242263
TI  - Rapidly deactivating AMPA receptors determine excitatory synaptic transmission to
      interneurons in the nucleus tractus solitarius from rat.
AB  - Excitatory synaptic transmission was investigated in interneurons of the
      parvocellular nucleus tractus solitarius (pNTS) by performing patch-clamp
      experiments in thin slice preparations from rat brain stem. Stimulation of single
      afferent fibers evoked excitatory postsynaptic currents (EPSCs) mediated by
      glutamate receptors of the DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic
      acid (AMPA) and N-methyl-D-aspartate types. AMPA-receptor-mediated EPSCs
      displayed decay time constants of 3.5 +/- 1.2 (SD) ms (13 cells), which were slow
      compared with EPSC decay time constants in neurons of the cerebellum or
      hippocampus. Slow EPSC decay was not explained by dendritic filtering, because
      the passive membrane properties of pNTS interneurons provided favorable voltage
      clamp conditions. Also, the slowness of EPSC decay did not result from slow
      deactivation of AMPA receptors (0.7 +/- 0.2 ms, 5 cells), which was investigated
      during rapid application of agonist to outside-out patches. Comparison of AMPA
      receptor kinetics with EPSC decay time constants suggested that the slow time
      course of EPSCs resulted from the prolonged presence of glutamate in the synaptic
      cleft.

PMID- 9242264
TI  - Passive properties of swimmeret motor neurons.
AB  - Four different functional types of motor neurons innervate each swimmeret: return
      stroke excitors (RSEs), power-stroke excitors (PSEs), return-stroke inhibitors
      (RSIs), and power-stroke inhibitors (PSIs). We studied the structures and passive
      electrical properties of these neurons, and tested the hypothesis that different
      types of motor neurons would have different passive properties that influenced
      generation of the swimmeret motor pattern. Cell bodies of neurons innervating one
      swimmeret were clustered in two anatomic groups in the same ganglion. The shapes
      of motor neurons in both groups were similar, despite the differences in
      locations of their cell bodies and in their functions. Diameters of their axons
      in the swimmeret nerve ranged from <2 to approximately 35 microm. Resting
      membrane potentials, input resistances, and membrane time constants were recorded
      with microelectrodes in the processes of swimmeret motor neurons in isolated
      abdominal nerve cord preparations. Membrane potentials had a median of -59 mV,
      with 25th and 75th percentiles of -66.0 and -53 mV. The median input resistance
      was 6.4 M omega, with 25th and 75th percentiles of 3.4 and 13.7 M omega. Membrane
      time constants had a median of 9.3 ms, with 25th and 75th percentiles of 5.7 and
      15.0 ms. Excitatory and inhibitory motor neurons had similar passive properties.
      RSE motor neurons were typically more depolarized than the other types, but the
      passive properties of RSE, PSE, RSI, and PSI neurons were not significantly
      different. Membrane time constants measured from cell bodies were briefer than
      those measured from neuropil processes, but membrane potentials and input
      resistances were not significantly different. The relative sizes of different
      motor neurons were measured from the sizes of their impulses recorded
      extracellularly from the swimmeret nerve. Smaller motor neurons had lower
      membrane potentials and were more likely to be active in the motor pattern than
      were large motor neurons. Motor neurons of different sizes had similar input
      resistances and membrane time constants. Motor neurons that were either
      oscillating or oscillating and firing in phase with the swimmeret motor pattern
      had lower average membrane potentials and longer time constants than those that
      were not oscillating. When the state of the swimmeret system changed from
      quiescence to continuous production of the motor pattern, the resting potentials,
      input resistances, and membrane time constants of individual swimmeret motor
      neurons changed only slightly. On average, both input resistance and membrane
      time constant increased. These similarities are considered in light of the
      functional task each motor neuron performs, and a hypothesis is developed that
      links the brief time constants of these neurons and graded synaptic transmission
      by premotor interneurons to control of the swimmeret muscles and the performance
      of the swimmeret system.

PMID- 9242265
TI  - Quantifying the role of inhibition in associative long-term potentiation in
      dentate granule cells with computational models.
AB  - In the dentate gyrus, coactivation of a mildly strong ipsilateral perforant path
      (pp) input with a weak contralateral pp input will not induce associative long
      term potentiation in the weak input path unless both inputs project to the same
      part of the molecular layer. This "spatial convergence requirement" is thought to
      arise from either voltage attenuation between input locations or inhibition.
      Simulations with a detailed model of a dentate granule cell were performed to
      rule out voltage attenuation and to quantify the inhibition necessary to obtain
      the spatial convergence requirement. Strong lateral and weak medial or strong
      medial and weak lateral pp input were activated eight times at 400 Hz. Calcium
      current through N-methyl-D-aspartate receptor channels and subsequent changes in
      calcium concentration and the concentration of calmodulin bound with four calcium
      ions ([Cal-Ca4]) in the spine head were computed for a medial and a lateral pp
      synapse. To satisfy the spatial convergence requirement, peak [Cal-Ca4] had to be
      much larger in the strongly activated path synapse than in the weakly activated
      path synapse. With no inhibition in the model, differences in peak [Cal-Cal4] at
      the two synapses were small, ruling out voltage attenuation as the explanation of
      the spatial convergence requirement. However, with shunting inhibition, modeled
      by reducing membrane resistivity to 1,600 omega cm2 in the distal two-thirds of
      the dendritic tree, peak [Cal-Ca4] was 3-5 times larger in the strongly activated
      path synapse than in the weakly activated path synapse. The magnitude of shunting
      inhibition was varied to determine the level that maximized this difference in
      peak [Cal-Ca4]. For strong lateral and weak medial pp input, the optimal level
      was one that prevented the cell from firing an action potential. For strong
      medial and weak lateral pp input, the optimal level was one at which the cell
      fired two action potentials. The distribution of shunting inhibition that best
      satisfied the spatial convergence requirement was inhibition on the distal two
      thirds of the dendritic tree with or without inhibition at the soma, with
      inhibition stronger in the distal third than in the middle third. It was
      estimated that the number of inhibitory synapses involved in the shunting
      inhibition should be 25-50% of the number of excitatory synapses activated by the
      eight-pulse, 400-Hz tetanus. This number could be 20-50% of the total number of
      inhibitory synapses in the distal two-thirds of the dendritic tree. The addition
      of a single inhibitory synapse on a dendrite had a significant effect on peak
      spine head [Cal-Ca4] in nearby spines. Inhibitory synapses had to be activated
      four or more times at 100 Hz for effective shunting to take place, and the
      inhibition had to begin no later than 2-5 ms after the first excitatory input.
      The results suggest that inhibition can isolate potentiated synapses to
      particular dendritic domains and that the location of activated inhibitory
      synapses may affect potentiation of individual synapses on individual dendrites.

PMID- 9242266
TI  - Control of forces applied by individual fingers engaged in restraint of an active
      object.
AB  - We investigated the coordination of fingertip forces in subjects who used the
      tips of two fingers to restrain an instrumented manipulandum with horizontally
      oriented grip surfaces. The grip surfaces were subjected to tangential pulling
      forces in the distal direction in relation to the fingers. The subjects used
      either the right index and middle fingers (unimanual grasp) or both index fingers
      (bimanual grasp) to restrain the manipulandum. To change the frictional condition
      at the digit-object interfaces, either both grip surfaces were covered with
      sandpaper or one was covered with sandpaper and the other with rayon. The forces
      applied normally and tangentially to the grip surfaces were measured separately
      at each plate along with the position of the plates. Subjects could have
      performed the present task successfully with many different force distributions
      between the digits. However, they partitioned the load in a manner that reflected
      the frictional condition at the local digit-object interfaces. When both digits
      contacted sandpaper, they typically partitioned the load symmetrically, but when
      one digit made contact with rayon and the other with sandpaper, the digit
      contacting the less slippery material (sandpaper) took up a larger part of the
      load. The normal forces were also influenced by the frictional condition, but
      they reflected the average friction at the two contact sites rather than the
      local friction. That is, when friction was low at one of the digit-object
      interfaces, only the applied normal forces increased at both digits. Thus sensory
      information related to the local frictional condition at the respective digit
      object interfaces controlled the normal force at both digits. The
      normal:tangential force ratio at each digit appeared to be a controlled variable.
      It was adjusted independently at each digit to the minimum ratio required to
      prevent frictional slippage, keeping an adequate safety margin against slippage.
      This was accomplished by the scaling of the normal forces to the average friction
      and by partitioning of the load according to frictional differences between the
      digit-object interfaces. In conclusion, by adjusting the normal:tangential force
      ratios to the local frictional condition, subjects avoided excessive normal
      forces at the individual digit-object interfaces, and by partitioning the load
      according the frictional difference, subjects avoided high normal forces. Thus
      the local frictional condition at the separate digit-object interfaces is one
      factor that can strongly influence the distribution of forces across digits
      engaged in a manipulative act.

PMID- 9242267
TI  - Electrophysiological properties of lumbar motoneurons in the alpha-chloralose
      anesthetized cat during carbachol-induced motor inhibition.
AB  - The present study was undertaken 1) to examine the neuronal mechanisms
      responsible for the inhibition of spinal cord motoneurons that occurs in alpha
      chloralose-anesthetized cats following the microinjection of carbachol into the
      nucleus pontis oralis (NPO), and 2) to determine whether the inhibitory
      mechanisms are the same as those that are responsible for the postsynaptic
      inhibition of motoneurons that is present during naturally occurring active
      sleep. Accordingly, the basic electrophysiological properties of lumbar
      motoneurons were examined, with the use of intracellular recording techniques, in
      cats anesthetized with alpha-chloralose and compared with those present during
      naturally occurring active sleep. The intrapontine administration of carbachol
      resulted in a sustained reduction in the amplitude of the spinal cord Ia
      monosynaptic reflex. Discrete large-amplitude inhibitory postsynaptic potentials
      (IPSPs), which are only present during the state of active sleep in the chronic
      cat, were also observed in high-gain recordings from lumbar motoneurons after the
      injection of carbachol. During carbachol-induced motor inhibition, lumbar
      motoneurons exhibited a statistically significant decrease in input resistance,
      membrane time constant and a reduction in the amplitude of the action potential's
      afterhyperpolarization. In addition, there was a statistically significant
      increase in rheobase and in the delay between the initial-segment (IS) and
      somadendritic (SD) portions of the action potential (IS-SD delay). There was a
      significant increase in the mean motoneuron resting membrane potential (i.e.,
      hyperpolarization). The preceding changes in the electrophysiological properties
      of motoneurons, as well as the development of discrete IPSPs, indicate that
      lumbar motoneurons are postsynaptically inhibited after the intrapontine
      administration of carbachol in cats that are anesthetized with alpha-chloralose.
      These changes in the electrophysiological properties of lumbar motoneurons were
      found to be comparable with those that take place during the atonia of active
      (rapid-eye-movement) sleep in chronic cats. The present results support the
      conclusion that the neural system that is responsible for motor inhibition during
      naturally occurring active sleep can also be activated in alpha-chloralose
      anesthetized cats following the injection of carbachol into the NPO.

PMID- 9242268
TI  - Dorsal spinocerebellar tract neurons are not subjected to postsynaptic inhibition
      during carbachol-induced motor inhibition.
AB  - Dorsal spinocerebellar tract (DSCT) neurons in Clarke's column in the lumbar
      spinal cord of cats anesthetized with alpha-chloralose were recorded
      intracellularly. The membrane potential activity and electrophysiological
      properties of these neurons were examined before and during the state of active
      sleep-like motor inhibition induced by the injection of carbachol into the
      nucleus pontis oralis. The synaptic activity of DSCT neurons during carbachol
      induced motor inhibition did not change compared with that during control
      conditions. In particular, there was an absence of inhibitory postsynaptic
      potentials (IPSPs) in high-gain recordings from DSCT neurons and the resting
      membrane potential of DSCT neurons was not significantly hyperpolarized during
      carbachol-induced motor inhibition. The mean amplitude of both monosynaptic
      excitatory postsynaptic potentials and disynaptic IPSPs evoked in DSCT neurons
      following stimulation of group I muscle afferents after the injection of
      carbachol was similar to that evoked before the injection of carbachol. There
      were no significant changes in the mean input resistance and membrane time
      constant of DSCT neurons during carbachol-induced motor inhibition. We conclude
      that, in contrast to lumbar motoneurons, DSCT neurons in Clarke's column are not
      postsynaptically inhibited during carbachol-induced motor inhibition. Therefore
      the population of spinal cord Ib interneurons that inhibit both DSCT neurons and
      lumbar motoneurons is not likely to be the interneurons that are responsible for
      the postsynaptic inhibition of motoneurons that occurs during carbachol-induced
      motor inhibition. The present findings also indicate that transmission through
      the DSCT is not modulated by postsynaptic inhibition at the level of DSCT neurons
      during carbachol-induced motor inhibition.

PMID- 9242269
TI  - Anticipatory time intervals of head-direction cells in the anterior thalamus of
      the rat: implications for path integration in the head-direction circuit.
AB  - Head-direction cells are neurons that signal a rat's directional heading in the
      horizontal plane. Head-direction cells in the anterior thalamus are anticipatory,
      so that their firing rate is better correlated with the rat's future head
      direction than with the present or past head direction. We recorded single-unit
      activity from head-direction cells in the anterior thalamus of freely moving
      rats. We measured the time interval by which each individual cell anticipated the
      rat's future head direction, which we refer to as the cell's anticipatory time
      interval (ATI). Head-direction cells in the anterior thalamus anticipated the
      rat's future head direction by an average ATI of approximately 17 ms. However,
      different anterior thalamic cells consistently anticipated the future head
      direction by different ATIs ranging between 0 and 50 ms. We found that the ATI of
      an anterior thalamic head-direction cell was correlated with several parameters
      of the cell's directional tuning function. First, cells with long ATIs sometimes
      appeared to have two peaks in their directional tuning function, whereas cells
      with short ATIs always had only one peak. Second, the ATI of a cell was
      negatively correlated with the cell's peak firing rate, so that cells with longer
      ATIs fired at a slower rate than cells with shorter ATIs. Third, a cell's ATI was
      correlated with the width of its directional tuning function, so that cells with
      longer ATIs had broader tuning widths than cells with shorter ATIs. These
      relationships between a cell's ATI and its directional tuning parameters could
      not be accounted for by artifactual broadening of the tuning function, which
      occurs for cells that fire in correlation with the future (rather than present)
      head direction. We found that when the rat's head is turning, the shape of an
      anterior thalamic head-direction cell's tuning function changes in a systematic
      way, becoming taller, narrower, and skewed. This systematic change in the shape
      of the tuning function may be what causes anterior thalamic cells to effectively
      anticipate the rat's future head direction. We propose a neural circuit mechanism
      to account for the firing behavior we have observed in our experiments, and we
      discuss how this circuit might serve as a functional component of a neural system
      for path integration of the rat's directional heading.

PMID- 9242270
TI  - Binaral interactions in the rat piriform cortex.
AB  - Single-unit recordings were made from layer II/III anterior piriform cortex
      (aPCX) neurons in adult Wistar rats to examine odor response patterns to
      unilaterally and bilaterally delivered stimuli. Isoamyl acetate odor stimulation
      was presented either unilaterally through tubes inserted into the external nares,
      or bilaterally during unilateral olfactory bulb lidocaine infusions. Olfactory
      bulb multiunit or slow-wave activity was recorded simultaneously bilaterally to
      monitor selectivity of unilateral odor stimulation. The results demonstrate that
      1) commissural input to aPCX neurons is sufficient to drive odor responses, and
      2) aPCX neurons can be classified on the basis of spatial receptive field type.
      These receptive fields include cells that respond 1) selectively to ipsilateral
      stimulation, 2) selectively to contralateral stimulation, 3) to either
      ipsilateral or contralateral stimulation, and 4) selectively to bilateral
      stimulation. The potential functions of binaral convergence in the piriform
      cortex are discussed, and may include enhancement of perceived odor intensity and
      bilateral access to olfactory memory.

PMID- 9242271
TI  - Pulmonary afferents are not necessary for the reflex inhibition of human
      inspiratory muscles produced by airway occlusion.
AB  - In contrast to limb muscles, the usual response of human inspiratory muscles to
      sudden loading consists of an initial marked reduction of electromyographic
      activity (EMG) followed by a subsequent increase in EMG. To determine
      definitively whether pulmonary receptors are necessary for this short-latency
      reflex inhibition produced by airway occlusion, we studied five subjects with
      complete pulmonary denervation due to bilateral transplantation of the lungs and
      five matched control subjects. Subjects with pulmonary denervation were studied
      between 10 and 50 days after transplantation (median 21 days). Brief airway
      occlusion during inspiration (i.e., loading; duration 250 ms) produced short
      latency reduction in EMG in the inspiratory muscles of all subjects with acute
      pulmonary denervation (scalenes and parasternal intercostal muscles; mean onset
      of inhibition 27 and 29 ms, respectively). The ongoing EMG was reduced by an
      average of 50% in scalenes and 36% in parasternal intercostal muscles. The size
      and the magnitude of the initial response did not differ significantly from those
      in control subjects. After the occlusion (i.e., unloading), activity of the
      inspiratory muscles was transiently reduced in control subjects and patients
      after bilateral lung transplantation. Given that the initial responses to airway
      loading and unloading were preserved after bilateral lung transplantation, we
      conclude that these reflex responses are not critically dependent on the
      discharge of intrapulmonary receptors. The results support the view that the
      short-latency inspiratory responses to loading and unloading can be mediated by
      inspiratory muscle afferents. They suggest a functionally different organization
      of the reflex pathways for inspiratory compared with limb muscles.

PMID- 9242272
TI  - Hyperpolarization-activated currents in the growth cone and soma of neonatal rat
      dorsal root ganglion neurons in culture.
AB  - Dissociated dorsal root ganglion neuron growth cones and somata from neonatal
      rats were voltage and current clamped with the use of the perforated-patch whole
      cell configuration to study the occurrence and properties of slow
      hyperpolarization-activated currents (Ih) at both regions. Under voltage-clamp
      conditions Ih, blockable by 2 mM extracellular CsCl, was present in 33% of the
      growth cones tested. Its steady-state activation as a function of voltage could
      be fitted with a single Boltzmann function with a midpoint potential of -97 mV.
      The time course of current activation could be best described by a double
      exponential function. The magnitude of the fully activated conductance was 3.5 nS
      and the reversal potential amounted to -29 mV. At the soma, Ih was found in 80%
      of the somata tested, which is much higher than occurrence at the growth cone.
      The steady-state activation curve of Ih at the soma, fitted with a single
      Boltzmann function, had a midpoint potential of -92 mV, which was more positive
      than that in the growth cone. The double-exponential activation of the current
      was faster than in the growth cone. The fully activated conductance of 5.1 nS and
      the reversal potential of -27 mV were not significantly different from the values
      obtained at the growth cone. Membrane hyperpolarization by current-clamp pulses
      elicited depolarizing sags in 30% and 78% of the tested growth cones and somata,
      respectively, which is in agreement with our voltage-clamp findings. Termination
      of the hyperpolarizing current pulse evoked a transient membrane depolarization
      or an action potential at both sites. Application of 2 mM extracellular CsCl
      hyperpolarized the membrane potential reversibly by approximately 5 mV and
      blocked the depolarizing sags and action potentials following the current
      injections at these regions. Thus Ih contributes to the resting membrane
      potential and modulates the excitability of both the growth cone and the soma.
      Intracellular perfusion with the second messenger adenosine 3',5'-cyclic
      monophosphate (cAMP) was only possible at the soma by the use of the conventional
      whole cell configuration. Addition of 100 microM cAMP to the pipette solution
      shifted the midpoint potential of the Ih activation curve from -108 to -78 mV.
      The current activation time course was also accelerated. The reversal potential
      and the fully activated conductance underlying Ih were not changed by cAMP. These
      results imply that cAMP primarily affects the gating kinetics of Ih. Our results
      show for the first time quantitative differences in Ih properties and occurrence
      at the growth cone and soma membrane. These differences may reflect differences
      in intracellular cAMP concentration and in the expression of Ih.

PMID- 9242273
TI  - Modification of current transmitted from apical dendrite to soma by blockade of
      voltage- and Ca2+-dependent conductances in rat neocortical pyramidal neurons.
AB  - The axial current transmitted to the soma during the long-lasting iontophoresis
      of glutamate at a distal site on the apical dendrite was measured by somatic
      voltage clamp of rat neocortical pyramidal neurons. Evidence for voltage- and
      Ca2+-gated channels in the apical dendrite was sought by examining the
      modification of this transmitted current resulting from the alteration of
      membrane potential and the application of channel-blocking agents. After N-methyl
      D-aspartate receptor blockade, iontophoresis of glutamate on the soma evoked a
      current whose amplitude decreased linearly with depolarization to an extrapolated
      reversal potential near 0 mV. Under the same conditions, glutamate iontophoresis
      on the apical dendrite 241-537 microm from the soma resulted in a transmitted
      axial current that increased with depolarization over the same range of membrane
      potential (about -90 to -40 mV). Current transmitted from dendrite to soma was
      thus amplified during depolarization from resting potential (about -70 mV) and
      attenuated during hyperpolarization. After Ca2+ influx was blocked to eliminate
      Ca2+-dependent K+ currents, application of 10 mM tetraethylammonium chloride
      (TEA) altered the amplitude and voltage dependence of the transmitted current in
      a manner consistent with the reduction of dendritic voltage-gated K+ current. We
      conclude that dendritic, TEA-sensitive, voltage-gated K+ channels can be
      activated by tonic dendritic depolarization. The most prominent effects of
      blocking Ca2+ influx resembled those elicited by TEA application, suggesting that
      these effects were caused predominantly by blockade of a dendritic Ca2+-dependent
      K+ current. When cells were impaled with microelectrodes containing ethylene
      glycol-bis(beta-amino-ethyl ether)-N,N',N'-tetraacetic acid to prevent a rise in
      intracellular Ca2+ concentration, blockade of Ca2+ influx altered the tonic
      transmitted current in different manner consistent with the blockade of an inward
      dendritic current carried by high-threshold-activated Ca2+ channels. We conclude
      that the primary effect of Ca2+ influx during tonic dendritic depolarization is
      the activation of a dendritic Ca2+-dependent K+ current. The hyperpolarizing
      attenuation of transmitted current was unaffected by blocking all known voltage
      gated inward currents except the hyperpolarization-activated cation current (Ih).
      Extracellular Cs+ (3 mM) reversibly abolished both the hyperpolarizing
      attenuation of transmitted current and Ih measured at the soma. We conclude that
      activation of Ih by hyperpolarization of the proximal apical dendrite would cause
      less axial current to arrive at the soma from a distal site than in a passive
      dendrite. Several functional implications of dendritic K+ and Ih channels are
      discussed.

PMID- 9242274
TI  - Stimulus-dependent modulation of spike burst length in cat striate cortical
      cells.
AB  - Burst activity, defined by groups of two or more spikes with intervals of < or =
      8 ms, was analyzed in responses to drifting sinewave gratings elicited from
      striate cortical neurons in anesthetized cats. Bursting varied broadly across a
      population of 507 simple and complex cells. Half of this population had > or =
      42% of their spikes contained in bursts. The fraction of spikes in bursts did not
      vary as a function of average firing rate and was stationary over time. Peaks in
      the interspike interval histograms were found at both 3-5 ms and 10-30 ms. In
      many cells the locations of these peaks were independent of firing rate,
      indicating a quantized control of firing behavior at two different time scales.
      The activity at the shorter time scale most likely results from intrinsic
      properties of the cell membrane, and that at the longer scale from recurrent
      network excitation. Burst frequency (bursts per s) and burst length (spikes per
      burst) both depended on firing rate. Burst frequency was essentially linear with
      firing rate, whereas burst length was a nonlinear function of firing rate and was
      also governed by stimulus orientation. At a given firing rate, burst length was
      greater for optimal orientations than for nonoptimal orientations. No organized
      orientation dependence was seen in bursts from lateral geniculate nucleus cells.
      Activation of cortical contrast gain control at low response amplitudes resulted
      in no burst length modulation, but burst shortening at optimal orientations was
      found in responses characterized by supersaturation. At a given firing rate,
      cortical burst length was shortened by microinjection of gamma-aminobutyric acid
      (GABA), and bursts became longer in the presence of N-methyl-bicuculline, a
      GABA(A) receptor blocker. These results are consistent with a model in which
      responses are reduced at nonoptimal orientations, at least in part, by burst
      shortening that is mediated by GABA. A similar mechanism contributes to response
      supersaturation at high contrasts via recruitment of inhibitory responses that
      are tuned to adjacent orientations. Burst length modulation can serve as a form
      of coding by supporting dynamic, stimulus-dependent reorganization of the
      effectiveness of individual network connections.

PMID- 9242275
TI  - Descending control of turning locomotor activity in larval lamprey:
      neurophysiology and computer modeling.
AB  - The purpose of the present study was to examine the mechanisms that produce
      natural spontaneous turning maneuvers in larval lamprey. During swimming,
      spontaneous turning movements began with a larger-than-normal bending of the head
      to one side. Subsequently, undulations propagated down the body with greater
      amplitude on the side ipsilateral to the turn. During turning to one side, which
      usually occurred within one cycle, the amplitude and duration of ipsilateral
      muscle burst activity as well as overall cycle time increased significantly with
      increasing turn angle. In in vitro brain/spinal cord preparations, brief
      electrical stimulation applied to the left side of the oral hood at the onset of
      locomotor burst activity on the right side of the spinal cord produced
      turninglike motor activity. During the perturbed cycle, the duration and
      amplitude of the burst on the right as well as cycle time were significantly
      larger than during preceding control cycles. In several lower vertebrates,
      unilateral stimulation in brain stem locomotor regions elicits asymmetric,
      turninglike locomotor activity. In the lamprey, unilateral chemical
      microstimulation in brain stem locomotor regions elicited continuous asymmetric
      locomotor activity, but there was little change in cycle time, as occurs during
      the single turning cycles in whole animals. The descending mechanisms responsible
      for producing turning locomotor activity were examined with the use of a computer
      model consisting of left and right phase oscillators in the spinal cord that were
      coupled by net reciprocal inhibition. With relatively weak reciprocal coupling, a
      brief unilateral descending excitatory input to one oscillator produced effects
      ipsilaterally, but there was little effect on the contralateral oscillator.
      Turninglike patterns could be produced by each of the following modifications of
      the model: 1) unilateral descending input and relatively strong reciprocal
      coupling; 2) unilateral descending input that phase shifted as well as increased
      the amplitude of the waveform generated by an oscillator on one side; and 3)
      brief descending modulatory inputs that excited the oscillator on one side and
      inhibited the contralateral oscillator. In all three cases, there was an increase
      in "burst" duration ipsilateral to the excitatory input and an increase in cycle
      time, similar to turning locomotor activity in whole animals. It is likely that
      turning maneuvers are mediated by descending modulatory inputs primarily to the
      spinal oscillator networks, which control the timing of burst activity, but
      perhaps also to motoneurons for axial musculature.

PMID- 9242276
TI  - Evidence of stimulus-dependent correlated activity in the dorsal cochlear nucleus
      of decerebrate gerbils.
AB  - Cross-correlation analysis of simultaneously recorded spike trains was used to
      study the internal organization of the dorsal cochlear nucleus (DCN) of
      unanesthetized decerebrate Mongolian gerbils. The goal was to test the model
      (adapted from cat) that its principal cells (type III and type IV units) receive
      three sources of shared auditory input: excitatory input from the auditory nerve;
      inhibitory input from DCN interneurons (vertical cells; type II and type II-i
      units) that respond vigorously to tones; and inhibitory input from ventral
      cochlear nucleus principal cells (D-stellate cells; wideband inhibitors) that
      conversely respond vigorously to noise. Records of spontaneous and/or driven
      activities (to long-duration tones and frozen broadband noise) were obtained for
      51 pairs consisting of type II, type III, and type IV units; type III units
      inhibited by low-level noise were subclassified as type III-i units. Pairs were
      isolated with two electrodes to study the effect of differences in unit best
      frequencies (BFs) on correlation. All correlated pairs composed of type III and
      type IV units (17 of 31 pairs) showed central mounds (CMs), indicative of shared
      input, in their cross-correlograms. These data exhibited two important
      properties: pairs with similar BFs were more likely to show CMs, and the shape of
      the CMs was stimulus dependent. That is, CM width typically changed sharply from
      wide to narrow with increasing level; significantly, transition-level CMs were
      either a composite of these shapes or not present. The transition to only narrow
      CMs occurred above the thresholds of type II and type III-i units to tones, but
      below their thresholds to noise. Cross-correlograms derived from the tone-evoked
      activities of pairs involving type II units (3 of 6 pairs) showed inhibitory
      troughs (ITs); unexpectedly, type III-i units were involved in both IT and CM
      pairs, suggesting that this unit type may reflect recordings from both vertical
      and principal cells. Overall, the results are interpretable in terms of the model
      of gerbil DCN that was adapted from cat, suggesting that the model generalizes
      across species. Compared with cat, however, gerbil principal cell responses
      (predominantly type III unit properties) are less dominated by inhibition.

PMID- 9242277
TI  - Physiological identification of the targets of cartwheel cells in the dorsal
      cochlear nucleus.
AB  - The integrative contribution of cartwheel cells of the dorsal cochlear nucleus
      (DCN) was assessed with intracellular recordings from anatomically identified
      cells. Recordings were made, in slices of the cochlear nuclei of mice, from 58
      cartwheel cells, 22 fusiform cells, 3 giant cells, 5 tuberculoventral cells, and
      1 cell that is either a superficial stellate or Golgi cell. Cartwheel cells can
      be distinguished electrophysiologically from other cells of the cochlear nuclei
      by their complex spikes, which comprised two to four rapid action potentials
      superimposed on a slower depolarization. The rapid action potentials were blocked
      by tetrodotoxin (n = 17) and were therefore mediated by voltage-sensitive sodium
      currents. The slow spikes were eliminated by the removal of calcium from the
      extracellular saline (n = 3) and thus were mediated by voltage-sensitive calcium
      currents. The spontaneous and evoked firing patterns of cartwheel cells were
      distinctive. Cartwheel cells usually fired single and complex spikes
      spontaneously at irregular intervals of between 100 ms and several seconds.
      Shocks to the DCN elicited firing that lasted tens to hundreds of milliseconds.
      With the use of these distinctive firing patterns, together with a
      pharmacological dissection of postsynaptic potentials (PSPs), possible targets of
      cartwheel cells were identified and the function of the connections was examined.
      Not only cartwheel and fusiform cells, but also giant cells, received patterns of
      synaptic input consistent with their having originated from cartwheel cells.
      These cell types responded to shocks of the DCN with variable trains of PSPs that
      lasted hundreds of milliseconds. PSPs within these trains appeared both singly
      and in bursts of two to four, and were blocked by 0.5 or 1 microM strychnine (n =
      4 cartwheel, 4 fusiform, and 2 giant cells), indicating that cartwheel cells are
      likely to be glycinergic. In contrast with cartwheel cells, which are weakly
      excited by glycinergic input, glycinergic PSPs consistently inhibited fusiform
      and giant cells. Tuberculoventral cells and the putative superficial stellate
      cell received little or no spontaneous synaptic activity. Shocks to the DCN
      evoked synaptic activity that lasted approximately 5 ms. These cells therefore
      probably do not receive input from cartwheel cells. In addition, the brief firing
      of tuberculoventral cells and of the putative superficial stellate cell in
      response to shocks indicates that these cells are unlikely to contribute to the
      late, glycinergic synaptic potentials observed in cartwheel, fusiform, and giant
      cells.

PMID- 9242278
TI  - Mechanical responses to two-tone distortion products in the apical and basal
      turns of the mammalian cochlea.
AB  - Mechanical responses to one- and two-tone acoustic stimuli were recorded from the
      cochlear partition in the apical turn of the chinchilla cochlea, the basal turn
      of the guinea pig cochlea, and the hook region of the guinea pig cochlea. The
      most sensitive or "best" frequencies (BFs) for the sites studied were
      approximately 500 Hz, 17 kHz, and 30 kHz, respectively. Responses to the cubic
      difference tone (CDT), 2F1 - F2 (where F1 and F2 are the frequencies of the
      primary stimuli), were characterized at each site. Responses to the quadratic
      difference tone (QDT), F2 - F1, were also characterized in the apical turn
      preparations (QDT responses were too small to measure in the basal cochlea). The
      observed responses to BF QDTs and CDTs and to BF CDTs at each site appeared
      similar in many ways; the relative magnitudes of the responses were highest at
      low-to-moderate sound pressure levels (SPLs), for example, and the absolute
      magnitudes grew nonmonotonically with increases in the level of either primary
      (L1 or L2) alone. The peak effective levels of the CDT and QDT responses were
      also similar, at around -20 dB re L1 and/or L2. In other respects, however, the
      responses to CDTs and QDTs and to BF CDTs at each site behaved quite differently.
      At low-to-moderate SPLs, for example, most CDT phase leads decreased with
      increases in either L1 or L2, whereas most QDT phase leads increased with
      increasing L1 and varied little with L2. Most CDT responses also varied
      monotonically with equal-level primaries (i.e., when L1 = L2), whereas most QDT
      responses varied nonmonotonically. Different responses also varied in different
      ways when F1 and F2 were varied. Apical turn QDT responses were observed over a
      very wide F1/F2 range (F1 = 1-12 kHz), but were usually largest for stimuli <2-4
      kHz. Apical turn CDT levels decreased (at rates of approximately 40-80 dB/octave)
      only when the frequency ratio F2/F1 increased beyond approximately 1.4-1.5. In
      the basal turn and hook regions, the CDT levels depended nonmonotonically on
      F2/F1 with the eventual rates of decrease being approximately 200 dB/octave.
      Optimal frequency ratios for the CDT increased from (F2 < 1.1F1) to (F2
      approximately 1.2F1) with increasing SPL in the basal turn, but were stable at
      around F2/F1 approximately 1.05 in the hook region. CDT phase leads tended to
      increase with increasing F2/F1 in all three regions of the cochlea, particularly
      at low-to-moderate SPLs. These findings are discussed in relation to previous
      studies of cochlear mechanics, physiology, and psychophysics.

PMID- 9242279
TI  - Wrist action affects precision grip force.
AB  - When moving objects with a precision grip, fingertip forces normal to the object
      surface (grip force) change in parallel with forces tangential to the object
      (load force). We investigated whether voluntary wrist actions can affect grip
      force independent of load force, because the extrinsic finger muscles cross the
      wrist. Grip force increased with wrist angular speed during wrist motion in the
      horizontal plane, and was much larger than the increased tangential load at the
      fingertips or the reaction forces from linear acceleration of the test object.
      During wrist flexion the index finger muscles in the hand and forearm increased
      myoelectric activity; during wrist extension this myoelectric activity increased
      little, or decreased for some subjects. The grip force maxima coincided with
      wrist acceleration maxima, and grip force remained elevated when subjects held
      the wrist in extreme flexion or extension. Likewise, during isometric wrist
      actions the grip force increased even though the fingertip loads remained
      constant. A grip force "pulse" developed that increased with wrist force rate,
      followed by a static grip force while the wrist force was sustained. Subjects
      could not suppress the grip force pulse when provided visual feedback of their
      grip force. We conclude that the extrinsic hand muscles can be recruited to
      assist the intended wrist action, yielding higher grip-load ratios than those
      employed with the wrist at rest. This added drive to hand muscles overcame any
      loss in muscle force while the extrinsic finger flexors shortened during wrist
      flexion motion. During wrist extension motion grip force increases apparently
      occurred from eccentric contraction of the extrinsic finger flexors. The
      coactivation of hand closing muscles with other wrist muscles also may result in
      part from a general motor facilitation, because grip force increased during
      isometric knee extension. However, these increases were related weakly to the
      knee force. The observed muscle coactivation, from all sources, may contribute to
      grasp stability. For example, when transporting grasped objects, upper limb
      accelerations simultaneously produce inertial torques at the wrist that must be
      resisted, and inertial loads at the fingertips from the object that must be
      offset by increased grip force. The muscle coactivation described here would
      cause similarly timed pulses in the wrist force and grip force. However, grip
      load coupling from this mechanism would not contribute much to grasp stability
      when small wrist forces are required, such as for slow movements or when the
      object's total resistive load is small.

PMID- 9242280
TI  - Synaptic physiology and mitochondrial function in crayfish tonic and phasic motor
      neurons.
AB  - Phasic and tonic motor neurons of crustaceans differ strikingly in their
      junctional synaptic physiology. Tonic neurons generally produce small excitatory
      postsynaptic potentials (EPSPs) that facilitate strongly as stimulation frequency
      is increased, and normally show no synaptic depression. In contrast, phasic
      neurons produce relatively large EPSPs with weak frequency facilitation and
      pronounced depression. We addressed the hypothesis that mitochondrial function is
      an important determinant of the features of synaptic transmission in these
      neurons. Mitochondrial fluorescence was measured with confocal microscopy in
      phasic and tonic axons and terminals of abdominal and leg muscles after exposure
      to supravital mitochondrial fluorochromes, rhodamine-123 (Rh123) and 4
      diethylaminostyryl-N-methylpyridinium iodide (4-Di-2-Asp). Mitochondria of tonic
      axons and neuromuscular junctions had significantly higher mean Rh123 and 4-Di-2
      Asp fluorescence than in phasic neurons, indicating more accumulation of the
      fluorochromes. Mitochondrial membrane potential, which is responsible for Rh123
      uptake and is related to mitochondrial oxidative activity (the production of ATP
      by oxidation of metabolic substrates), is likely higher in tonic axons. Electron
      microscopy showed that tonic axons contain approximately fivefold more
      mitochondria per microm2 cross-sectional area than phasic axons. Neuromuscular
      junctions of tonic axons also have a much higher mitochondrial content than those
      of phasic axons. We tested the hypothesis that synaptic fatigue resistance is
      dependent on mitochondrial function in crayfish motor axons. Impairment of
      mitochondrial function by uncouplers of oxidative phosphorylation, dinitrophenol
      or carbonyl cyanide m-chlorophenylhydrazone, or by the electron transport
      inhibitor sodium azide, led to marked synaptic depression of a tonic axon and
      accelerated depression of a phasic axon during maintained stimulation.
      Iodoacetate, an inhibitor of glycolysis, and chloramphenicol, a mitochondrial
      protein synthesis inhibitor, had no significant effects on either mitochondrial
      fluorescence or synaptic depression in tonic or phasic axons. Collectively, the
      results provide evidence that mitochondrial oxidative metabolism is important for
      sustaining synaptic transmission during maintained stimulation of tonic and
      phasic motor neurons. Tonic neurons have a higher mitochondrial content and
      greater oxidative activity; these features are correlated with their greater
      resistance to synaptic depression. Conversely, phasic neurons have a lower
      mitochondrial content, less oxidative activity, and greater synaptic
      fatigability.

PMID- 9242281
TI  - Effects of the gliotoxin fluorocitrate on spreading depression and glial membrane
      potential in rat brain in situ.
AB  - DC extracellular potential shifts (deltaVo) associated with spreading depression
      (SD) reflect massive cell depolarization, but their cellular generators remain
      obscure. We have recently reported that the glial specific metabolic poison
      fluorocitrate (FC) delivered by microdialysis in situ caused a rapid impairment
      of glial function followed some hours later by loss of neuronal electrogenic
      activity and neuron death. We have used the time windows for selective decay of
      cell types so created to study the relative participation of glia and neurons in
      SD, and we report a detailed analysis of the effects of FC on evoked SD waves and
      glial membrane potential (Vm). Extracellular potential (Vo), interstitial
      potassium concentration ([K+]o), evoked potentials, and transmembrane glial
      potentials were monitored in the CA1 area before, during, and after
      administration of FC with or without elevated K+ concentration in the dialysate.
      SD waves propagated faster and lasted longer during FC treatment. DeltaVo in
      stratum pyramidale, which normally are much shorter and of smaller amplitude than
      those in stratum radiatum, expanded during FC treatment to match those in stratum
      radiatum. The coalescing SD waves that develop late during prolonged high-K+
      dialysis and are typically limited to stratum radiatum, also expanded into
      stratum pyramidale under the influence of FC. SD provoked in neocortex normally
      does not spread to the CA1, but during FC treatment it readily reached CA1 via
      entorhinal cortex. Once neuronal function began to deteriorate, SD waves became
      smaller and slower, and eventually failed to enter the region around the FC
      source. Slow, moderately negative deltaVo that mirrored [K+]o increments could
      still be recorded well after neuronal function and SD-associated Vo had
      disappeared. Glial cell Vm gradually depolarized during FC administration,
      beginning much before depression of neuronal antidromic action potentials.
      Calculations based on the results predict a large decrease in glial potassium
      content during FC treatment. The results are compatible with neurons being the
      major generator of the deltaVo associated with SD. We conclude that energy
      shortage in glial cells makes brain tissue more susceptible to SD and therefore
      it may increase the risk of neuron damage.

PMID- 9242282
TI  - Coordination of startle and swimming neural systems in the pteropod mollusk
      Clione limacina: role of the cerebral cholinergic interneuron.
AB  - The holoplanktonic pteropod mollusk Clione limacina has a unique startle system
      that provides a very fast, ballistic movement of the animal during escape or prey
      capture behaviors. The startle system consists of two groups of large pedal
      motoneurons that control ventral or dorsal flexions of the wings. Although
      startle motoneurons innervate the same musculature used during normal swimming,
      they are independent of the swim central pattern generator and swim motoneurons.
      This study demonstrates that a cerebral startle (Cr-St) interneuron, which
      provides prominent excitatory inputs to startle motoneurons, plays a very
      important role in coordination of the startle and swimming neural systems. The Cr
      St interneuron produces, simultaneously with monosynaptic excitatory inputs to
      dorsal startle motoneurons, monosynaptic inhibitory inputs to all types of swim
      neurons, including interneurons of the central pattern generator, general excitor
      motoneurons, small motoneurons, and modulatory pedal serotonergic wing neurons.
      The inhibitory synaptic transmission between the Cr-St interneuron and swim
      interneurons and motoneurons, as well as excitatory transmission between the Cr
      St interneuron and startle motoneurons, appears to be cholinergic because it is
      blocked by the cholinergic antagonists atropine and d-tubocurarine, mimicked by
      exogenous acetylcholine in very low concentrations, and enhanced by the
      cholinesterase inhibitor eserine (physostigmine). The Cr-St-neuron-mediated
      inhibitory inputs to the swimming system are strong enough to completely
      terminate swimming activity while the Cr-St interneuron is active. Mechanosensory
      inputs are capable of triggering Cr-St neuron firing at rates sufficient to
      suppress fictive swimming in reduced preparations. Thus the Cr-St interneuron can
      temporally remove the swimming system from the control over the swim musculature
      while simultaneously activating the startle system to produce a powerful, short
      latency response.

PMID- 9242283
TI  - Differing mechanisms of expression for short- and long-term potentiation.
AB  - Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that
      is of great interest as a cellular mechanism that may contribute to memory
      storage. It is the sustained phase of population excitatory postsynaptic
      potential induced by high-frequency stimulation (HFS). HFS can also induce short
      term potentiation (STP), a decremental potentiation lasting approximately 15 min.
      It has been unclear whether STP is simply a reversible form of LTP elicited by
      subthreshold stimuli or whether it is an independently expressed form of synaptic
      plasticity. We have attempted to clarify the relationship between LTP and STP in
      the extracellular recording technique in area CA1 of the adult rat hippocampal
      slice preparation to test four predictions of the hypothesis that LTP and STP are
      expressed via the same mechanism. First, occluding LTP expression should block
      STP expression. Saturating LTP under six different conditions, however, did not
      occlude STP expression. Second, occluding STP expression should occlude LTP
      expression. The partial or full occlusion of STP by two maneuvers (increasing the
      stimulus intensity used for HFS or applying 3-isobutyl-1-methylxanthine),
      however, did not occlude LTP expression. Third, LTP increases and decreases
      paired-pulse facilitation (PPF), and STP should have the same effect. STP did not
      change PFF, however. The first three results, then, suggest that STP and LTP are
      expressed via different mechanisms. Fourth, STP should be maximal near the LTP
      induction threshold, and then decrease above it. Surprisingly, STP was maximal at
      or very close to the LTP induction threshold, but it did not decrease above this
      threshold. This relationship suggests the possibility that STP and LTP share an
      induction step(s). What is the function of the independently expressed STP? We
      find that LTP can be induced by two HFSs, each of which is subthreshold for LTP,
      if the second is given during STP from the first. This suggests that STP can
      temporarily lower the LTP induction threshold. Three lines of evidence, then,
      suggest that STP and LTP may be expressed via different mechanisms; however, the
      proximity of STP saturation to LTP induction suggests that they may share an
      induction step(s). STP may also have the very important function of temporarily
      lowering the LTP induction threshold. Finally, these data suggestion caution in
      interpreting LTP data obtained <20-30 min after HFS, because they may be
      contaminated by STP, which appears to have different underlying mechanisms.

PMID- 9242284
TI  - Intracellular and computational characterization of the intracortical inhibitory
      control of synchronized thalamic inputs in vivo.
AB  - We investigated the presence and role of local inhibitory cortical control over
      synchronized thalamic inputs during spindle oscillations (7-14 Hz) by combining
      intracellular recordings of pyramidal cells in barbiturate-anesthetized cats and
      computational models. The recordings showed that 1) similar excitatory
      postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences
      occurred either during spindles or following thalamic stimulation; 2) reversed
      IPSPs with chloride-filled pipettes transformed spindle-related EPSP/IPSP
      sequences into robust bursts with spike inactivation, resembling paroxysmal
      depolarizing shifts during seizures; and 3) dual simultaneous impalements showed
      that inhibition associated with synchronized thalamic inputs is local.
      Computational models were based on reconstructed pyramidal cells constrained by
      recordings from the same cells. These models showed that the transformation of
      EPSP/IPSP sequences into fully developed spike bursts critically needs a
      relatively high density of inhibitory currents in the soma and proximal
      dendrites. In addition, models predict significant Ca2+ transients in dendrites
      due to synchronized thalamic inputs. We conclude that synchronized thalamic
      inputs are subject to strong inhibitory control within the cortex and propose
      that 1) local impairment of inhibition contributes to the transformation of
      spindles into spike-wave-type discharges, and 2) spindle-related inputs trigger
      Ca2+ events in cortical dendrites that may subserve plasticity phenomena during
      sleep.

PMID- 9242285
TI  - Binocular spatial phase tuning characteristics of neurons in the macaque striate
      cortex.
AB  - We employed microelectrode recording techniques to study the sensitivity of
      individual neurons in the striate cortex of anesthetized and paralyzed monkeys to
      relative interocular image disparities and to determine the effects of basic
      stimulus parameters on these cortical binocular interactions. The visual stimuli
      were drifting sine wave gratings. After the optimal stimulus orientation, spatial
      frequency, and direction of stimulus movement were found, the cells' disparity
      tuning characteristics were determined by measuring responses as a function of
      the relative interocular spatial phase of dichoptic grating pairs. No attempts
      were made to assess absolute position disparities or horizontal disparities
      relative to the horopter. The majority (approximately 70%) of simple cells were
      highly sensitive to interocular spatial phase disparities, particularly neurons
      with balanced ocular dominances. Simple cells typically demonstrated binocular
      facilitation at the optimal phase disparity and binocular suppression for
      disparities 180 degrees away. Fewer complex cells were phase selective
      (approximately 40%); however, the range of disparity selectivity in phase
      sensitive complex cells was comparable with that for simple cells. Binocular
      interactions in non-phase-sensitive complex cells were evidenced by binocular
      response amplitudes that differed from responses to monocular stimulation. The
      degree of disparity tuning was independent of a cell's optimal orientation or the
      degree of direction tuning. However, disparity-sensitive cells tended to have
      narrow orientation tuning functions and the degree of disparity tuning was
      greatest for the optimal stimulus orientations. Rotating the stimulus for one eye
      90 degrees from the optimal orientation usually eliminated binocular
      interactions. The effects of phase disparities on the binocular response
      amplitude were also greatest at the optimal spatial frequency. Thus a cell's
      sensitivity to absolute position disparities reflects its spatial tuning
      characteristics, with cells sensitive to high spatial frequencies being capable
      of signaling very small changes in image disparity. On the other hand, stimulus
      contrast had relatively little effect on a cell's disparity tuning, because
      response saturation occurred at the same contrast level for all relative
      interocular phase disparities. Thus, as with orientation tuning, a cell's optimal
      disparity and the degree of disparity selectivity were invariant with contrast.
      Overall, the results show that sensitivity to interocular spatial phase
      disparities is a common property of striate neurons. A cell's disparity tuning
      characteristics appear to largely reflect its monocular receptive field
      properties and the interocular balance between excitatory and inhibitory inputs.
      However, distinct functional classes of cortical neurons could not be
      discriminated on the basis of disparity sensitivity alone.

PMID- 9242286
TI  - Binocular combination of contrast signals by striate cortical neurons in the
      monkey.
AB  - With the use of microelectrode recording techniques, we investigated how the
      contrast signals from the two eyes are combined in individual cortical neurons in
      the striate cortex of anesthetized and paralyzed macaque monkeys. For a given
      neuron, the optimal spatial frequency, orientation, and direction of drift for
      sine wave grating stimuli were determined for each eye. The cell's disparity
      tuning characteristics were determined by measuring responses as a function of
      the relative interocular spatial phase of dichoptic stimuli that consisted of the
      optimal monocular gratings. Binocular contrast summation was then investigated by
      measuring contrast response functions for optimal dichoptic grating pairs that
      had left- to right-eye interocular contrast ratios that varied from 0.1 to 10.
      The goal was to determine the left- and right-eye contrast components required to
      produce a criterion threshold response. For all functional classes of cortical
      neurons and for both cooperative and antagonistic binocular interactions, there
      was a linear relationship between the left- and right-eye contrast components
      required to produce a threshold response. Thus, for example for cooperative
      binocular interactions, a reduction in contrast to one eye was counterbalanced by
      an equivalent increase in contrast to the other eye. These results showed that in
      simple cells and phase-specific complex cells, the contrast signals from the two
      eyes were linearly combined at the subunit level before nonlinear rectification.
      In non-phase-specific complex cells, the linear binocular convergence of contrast
      signals could have taken place either before or after the rectification process,
      but before spike generation. In addition, for simple cells, vector analysis of
      spatial summation showed that the inputs from the two eyes were also combined in
      a linear manner before nonlinear spike-generating mechanisms. Thus simple cells
      showed linear spatial summation not only within and between subregions in a given
      receptive field, but also between the left- and right-eye receptive fields.
      Overall, the results show that the effectiveness of a stimulus in producing a
      response reflects interocular differences in the relative balance of inputs to a
      given cell, however, the eye of origin of a light-evoked signal has no specific
      consequence.

PMID- 9242287
TI  - Developmental changes in the hypoxic response of the hypoglossus respiratory
      motor output in vitro.
AB  - The transverse brain stem slice of mice containing the pre-Botzinger complex
      (PBC), a region essential for respiratory rhythm generation in vitro, was used to
      study developmental changes of the response of the in vitro respiratory network
      to severe hypoxia (anoxia). This preparation generates, at different postnatal
      stages [postnatal day (P)0-22], spontaneous rhythmic activity in hypoglossal
      (XII) rootlets that are known to occur in synchrony with periodic bursts of
      neurons in the PBC. It is assumed that this rhythmic activity reflects
      respiratory rhythmic activity. At all examined stages anoxia led to a biphasic
      response: the frequency of rhythmic XII activity initially increased ("primary
      augmentation") and then decreased ("secondary depression"). In neonates (P0-7),
      anoxia did not significantly affect the amplitude of integrated XII bursts.
      Secondary depression never led to a cessation of rhythmic activity. In mice older
      than P7, augmentation was accompanied by a significant increase in the amplitude
      of XII bursts. A significant decrease of the amplitude of XII bursts occurred
      during secondary depression. This depression led always to cessation of rhythmic
      activity in XII rootlets. The anoxia-induced response of the respiratory rhythmic
      XII motor output is biphasic and changes during development in a similar way to
      the in vivo respiratory network. Whether this biphasic response is due to a
      biphasic response of the respiratory rhythm generator and/or to a biphasic
      modulation of the XII motor nucleus remains unresolved and needs further cellular
      analysis. We propose that the transverse slice is a useful model system for
      examination of the mechanisms underlying the hypoxic response.

PMID- 9242288
TI  - GABAergic modulation of hippocampal population activity: sequence learning, place
      field development, and the phase precession effect.
AB  - A detailed biophysical model of hippocampal region CA3 was constructed to study
      how GABAergic modulation influences place field development and the learning and
      recall of sequence information. Simulations included 1,000 multicompartmental
      pyramidal cells, each consisting of seven intrinsic and four synaptic currents,
      and 200 multicompartmental interneurons, consisting of two intrinsic and four
      synaptic currents. Excitatory rhythmic septal input to the apical dendrites of
      pyramidal cells and both excitatory and inhibitory input to interneurons at theta
      frequencies provided a cellular basis for the development of theta and gamma
      frequency oscillations in population activity. The fundamental frequency of theta
      oscillations was dictated by the driving rhythm from the septum. Gamma
      oscillation frequency, however, was determined by both the decay time of the
      gamma-aminobutyric acid-A (GABA(A))-receptor-mediated synaptic current and the
      overall level of excitability in interneurons due to alpha-amino-3-hydroxy-5
      methyl-4-isoxazole proprionic acid and N-methyl-D-aspartate (NMDA)-receptor-gated
      channel activation. During theta population activity, total GABA(B)-receptor
      mediated conductance levels were found to gradually rise and fall in rhythmic
      fashion with the predominant population frequency (theta rhythm). This resulted
      in periodic GABA(B)-receptor-mediated suppression of excitatory synaptic
      transmission at recurrent collaterals (intrinsic fibers) of pyramidal cells and
      suppression of inhibitory synaptic transmission to both pyramidal cells and
      interneurons. To test the ability of the model to learn and recall temporal
      sequence information, a completion task was employed. During learning, the
      network was presented a sequence of nonorthogonal spatial patterns. Each input
      pattern represented a spatial "location" of a simulated rat running a specific
      navigational path. Hebbian-type learning was expressed as an increase in
      postsynaptic NMDA-receptor-mediated conductances. Because of several factors
      including the sparse, asymmetric excitatory synaptic connections among pyramidal
      cells in the model and a sufficient degree of random "background" firing
      unrelated to the input patterns, repeated simulated runs resulted in the gradual
      emergence of place fields where a given cell began to respond to a contiguous
      segment of locations on the path. During recall, the simulated rat was placed at
      a random location on the previously learned path and tested to see whether the
      sequence of locations could be completed on the basis of this initial position.
      Periodic GABA(B)-receptor-mediated suppression of excitatory and inhibitory
      transmission at intrinsic but not afferent fibers resulted in sensory information
      about location being dominant during early portions of each theta cycle when
      GABA(B)-receptor-related effects were highest. This suppression declined with
      levels of GABA(B) receptor activation toward the end of a theta cycle, resulting
      in an increase in synaptic transmission at intrinsic fibers and the subsequent
      recall of a segment of the entire location sequence. This scenario typically
      continued across theta cycles until the full sequence was recalled. When the
      GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission
      at intrinsic fibers was not included in the model, place field development was
      curtailed and the network consequently exhibited poor learning and recall
      performance. This was, in part, due to increased competition of information from
      intrinsic and afferent fibers during early portions of each theta cycle. Because
      afferent sensory information did not dominate early in each cycle, the current
      location of the rat was obscured by ongoing activity from intrinsic sources.
      (ABSTRACT TRUNCATED)

PMID- 9242289
TI  - Role of calcium-calmodulin-dependent protein kinase II in modulation of
      sensorimotor synapses in Aplysia.
AB  - The Ca2+-calmodulin-dependent protein kinase II (CaMKII) inhibitor, [1-[N,O-bis(5
      isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne) (KN-62), was used
      to investigate the role of CaMKII in synaptic transmission and serotonin (5-HT)
      induced facilitation in Aplysia. Application of KN-62 (10 microM) by itself
      increased the amplitude of excitatory postsynaptic potentials (EPSPs) at
      sensorimotor synapses in pleural-pedal ganglia. Moreover, in the presence of KN
      62, 5-HT-induced short-term facilitation was attenuated. Application of KN-62 by
      itself slightly increased the duration of action potentials in isolated sensory
      neuron somata but did not block spike broadening produced by 5-HT. KN-62 had no
      effect on excitability of isolated sensory neuron somata nor did it block 5-HT
      induced enhancement of excitability. These results indicate that the attenuation
      of short-term facilitation by KN-62 is not due to modulation of the membrane
      currents contributing to 5-HT-induced spike broadening or enhancement of
      excitability. Rather, these data are consistent with the hypothesis that CaMKII
      contributes to the regulation of sensorimotor connections and that it has a role
      in spike-duration-independent processes contributing to short-term facilitation.

PMID- 9242290
TI  - Facilitation at the lobster neuromuscular junction: a stimulus-dependent
      mobilization model.
AB  - Frequency facilitation is a process whereby neurosecretion increases as a
      function of stimulation frequency during repetitive synaptic activity. To examine
      the physiological basis underlying facilitation, we have estimated the frequency
      dependence of the synaptic parameters n (number of units capable of responding to
      a nerve impulse) and P (average probability of responding) at the lobster
      neuromuscular junction. Both n and P increase as a function of frequency,
      suggesting that the efficiency of quantal docking and quantal fusion is regulated
      by repetitive synaptic activity. In experiments in which facilitation is strong
      and quantal content does not saturate over the frequency range tested, the value
      of P saturates at low frequencies of stimulation, and increases in quantal
      content at higher frequencies of stimulation are due to an increase in n.
      Therefore the value of P does not limit facilitation. We propose that transmitter
      release is limited by the rates of quantal mobilization and demobilization, and
      that each excitatory stimulus causes additional mobilization of quanta to dock at
      the presynaptic release sites. In such a model the binomial parameter n will
      correspond to the number of quanta docked at the release sites and available for
      release. We have developed and solved kinetic equations that describe how the
      number of docked quanta changes as a function of time and of stimulation
      frequency. The stimulus-dependent mobilization model of facilitation predicts
      that the reciprocal value of the quantal content depends linearly on the
      reciprocal product of the stimulation frequency and the probability of release.
      Fits of the experimental data confirm the accuracy of this prediction, showing
      that the model proposed here quantitatively describes frequency facilitation. The
      model predicts that high rates of quantal demobilization will produce strong
      frequency facilitation.

PMID- 9242291
TI  - Differential control of reciprocal inhibition during walking versus postural and
      voluntary motor tasks in humans.
AB  - Experiments were done to determine whether the strength of reciprocal inhibition
      from ankle flexors to extensors can be controlled independently of the level of
      ongoing motor activity in a task-dependent manner. In this paper we use the term
      reciprocal inhibition in the functional sense--inhibition of the antagonist(s)
      during activity of the agonist(s)--without reference to specific neural pathways
      that may be involved. The strength of reciprocal inhibition of the soleus alpha
      motoneurons was determined by measuring the amplitude of the H reflex during
      voluntary, postural, and locomotor tasks requiring activity of the ankle flexor
      tibialis anterior (TA). Differences in the strength of reciprocal inhibition
      between tasks were determined from plots of the soleus H reflex amplitude versus
      the mean value of the TA electromyogram (EMG). Additionally, in tasks involving
      movement, the correlation between the H reflex amplitude and the joint kinematics
      was calculated. In most subjects (15 of 22) the soleus H reflex decreased
      approximately linearly with increasing tonic voluntary contractions of the TA.
      The H reflex also decreased approximately linearly with the TA EMG activity when
      subjects where asked to lean backward. There were no statistical differences
      between the regression lines obtained in these tasks. In some subjects (7 of 22),
      however, the H reflex amplitude was independent of the level of TA EMG activity,
      except for a sudden drop at high levels of TA activity (approximately 60-80% of
      maximum voluntary contraction). The type of relation between the soleus H reflex
      and the TA EMG activity in these tasks was not correlated with the maximum H
      reflex to maximum M wave (Hmax/Mmax) ratio measured during quiet standing. In
      marked contrast, during the swing phase of walking--over the same range of TA EMG
      activity as during the tonic voluntary contraction task--the H reflex was reduced
      to zero in most subjects (24 of 31). In seven subjects the H reflex during the
      swing phase was reduced to some 5% of the value during quiet standing. The same
      result was found when subjects were asked to produce a stepping movement with one
      leg (OLS) in response to an auditory "go" signal. Additionally, in the OLS task
      it was possible to examine the behavior of the H reflex during the reaction time
      and thus to evaluate the relative contribution of central commands versus
      movement-related afferent activity to the inhibition of the soleus H reflex. In
      11 of 12 subjects the H reflex attained its minimum value before either the onset
      of EMG activity or movement of any of the leg joints. It is significant that the
      H reflex was most powerfully inhibited during the swing phase of walking and the
      closely related OLS task. The H reflex was also measured during isolated ankle
      dorsiflexion movements. The subjects were asked to track a target displayed on a
      computer screen with dorsiflexion movements of the ankle. The trajectory of the
      target was the same as that of the ankle during the swing phase of walking. The
      soleus H reflexes were intermediate in size between the values obtained in the
      tonic contraction task and the walking or OLS tasks. A negative, but weak,
      correlation (r2 < 0.68) between the soleus H reflex and the TA EMG was found in 3
      of 10 subjects. Furthermore, there was no correlation between the H reflex
      amplitude and the ankle angular displacement or angular velocity. In this task,
      as in the OLS task, the H reflex began to decrease during the reaction time
      before the onset of TA EMG activity. We conclude that the strength of reciprocal
      inhibition of the soleus alpha-motoneuron pool can thus be controlled
      independently of the level of motor activity in the ankle flexors. The strength
      of the inhibition of the antagonist(s) depends on the task, and for each task the
      strength of the inhibition is not necessarily proportional to the level of motor
      activity in the agonist(s). (ABSTRACT TRUNCATED)

PMID- 9242292
TI  - Endogenous activation of dopamine D2 receptors regulates dopamine release in the
      fish retina.
AB  - In the fish retina, horizontal cell electrical coupling and light responsiveness
      is regulated by activation of dopamine D1 receptors that are located on the
      horizontal cells themselves. The effects of dopamine and dopamine D2 receptor
      agonists and antagonists on cone horizontal cell light responses were studied in
      in vitro superfused goldfish retinas. Horizontal cell light responses and
      electrical coupling were assessed by monitoring responses to full-field stimuli
      and to small, centered (0.4 mm diam) spots of light, respectively. Dopamine (0.2
      10 microM) application uncoupled horizontal cells and decreased their responses
      to full-field stimuli. Application of the D2 antagonist eticlopride (10-50
      microM) produced similar effects, whereas quinpirole (0.1-10 microM), a D2
      agonist, had the opposite effects. The uncoupling effect of eticlopride was
      blocked by prior application of SCH23390 (10 microM), a D1 receptor antagonist,
      and was eliminated after destruction of dopaminergic neurons by prior treatment
      of the retinas with 6-hydroxydopamine. The effects of these D2 drugs were
      observed following flickering light stimulation, but were not observed following
      sustained light stimulation. Application of the D2 antagonists sulpiride (0.5-20
      microM) and spiperone (0.25-10 microM) uncoupled horizontal cells when the total
      concentration of divalent cations (Mg2+ and Ca2+) in the Ringer solution was 1.1
      mM. However, when the concentration of divalent cations was 0.2 mM, spiperone had
      no effect on the horizontal cells and sulpiride increased coupling. In contrast,
      eticlopride uncoupled the cells and decreased their light responsiveness
      irrespective of the concentration of divalent cations. The effects of quinpirole
      also depended on the concentration of divalent cations; its coupling effect was
      reduced when the divalent cation concentration was increased from 0.2 to 1.0 mM.
      The results suggest that activation of D2 receptors in the fish retina by
      endogenous dopamine decreases dopamine release and is greater after flickering
      compared with sustained light stimulation. These D2 receptors thus function as
      presynaptic autoreceptors that inhibit dopamine release from dopaminergic cells.
      In addition, the results also indicate that the effectiveness of some D2 drugs at
      these receptors is dependent on the concentration of divalent cations.

PMID- 9242293
TI  - Cerebral processing of acute skin and muscle pain in humans.
AB  - The human cerebral processing of noxious input from skin and muscle was compared
      with the use of positron emission tomography with intravenous H2(15)O to detect
      changes in regional cerebral blood flow (rCBF) as an indicator of neuronal
      activity. During each of eight scans, 11 normal subjects rated the intensity of
      stimuli delivered to the nondominant (left) forearm on a scale ranging from 0 to
      100 with 70 as pain threshold. Cutaneous pain was produced with a high-energy CO2
      laser stimulator. Muscle pain was elicited with high-intensity intramuscular
      electrical stimulation. The mean ratings of perceived intensity for innocuous and
      noxious stimulation were 32.6 +/- 4.5 (SE) and 78.4 +/- 1.7 for cutaneous
      stimulation and 15.4 +/- 4.2 and 73.5 +/- 1.4 for intramuscular stimulation. The
      pain intensity ratings and the differences between noxious and innocuous ratings
      were similar for cutaneous and intramuscular stimuli (P > 0.05). After
      stereotactic registration, statistical pixel-by-pixel summation (Z score) and
      volumes-of-interest (VOI) analyses of subtraction images were performed.
      Significant increases in rCBF to both noxious cutaneous and intramuscular
      stimulation were found in the contralateral secondary somatosensory cortex (SII)
      and inferior parietal lobule [Brodmann area (BA) 40]. Comparable levels of rCBF
      increase were found in the contralateral anterior insular cortex, thalamus, and
      ipsilateral cerebellum. Noxious cutaneous stimulation caused significant
      activation in the contralateral lateral prefrontal cortex (BA 10/46) and
      ipsilateral premotor cortex (BA 4/6). Noxious intramuscular stimulation evoked
      rCBF increases in the contralateral anterior cingulate cortex (BA 24) and
      subsignificant responses in the contralateral primary sensorimotor cortex (MI/SI)
      and lenticular nucleus. These activated cerebral structures may represent those
      recruited early in nociceptive processing because both forms of stimuli were near
      pain threshold. Correlation analyses showed a negative relationship between
      changes in rCBF for thalamus and MI/SI for cutaneous stimulation, and positive
      relationships between thalamus and anterior insula for both stimulus modalities.
      Direct statistical comparisons between innocuous cutaneous and intramuscular
      stimulation with the use of Z scores and VOI analyses showed no reliable
      differences between these two forms of noxious stimulation, indicating a
      substantial overlap in brain activation pattern. The comparison of noxious
      cutaneous and intramuscular stimulation indicated more activation in the premotor
      cortex, SII, and prefrontal cortex with cutaneous stimulation, but these
      differences did not reach statistical significance. The similar cerebral
      activation patterns suggest that the perceived differences between acute skin and
      muscle pain are mediated by differences in the intensity and temporospatial
      pattern of neuronal activity within similar sets of forebrain structures.

PMID- 9242294
TI  - Postnatal development of ionic currents in rat hippocampal astrocytes in situ.
AB  - Developmental changes in ion channel expression and cell morphology were studied
      in glial cells with the use of whole cell patch-clamp recordings in rat
      [postnatal day (P)5-P50] hippocampal slices. Recordings were obtained from 234
      cells, presumed to be glia, in stratum radiatum and stratum lacunosum-moleculare
      of the CA1 region. Of 66 recorded cells filled with Lucifer yellow, 48 stained
      positive for glial fibrillary acidic protein, which identified them as
      astrocytes. All glial cells studied were of a stellate morphology, and
      developmental changes primarily comprised an increase in the length and number of
      cell processes associated with an overall increase in cell size and membrane
      capacitance. Two distinct outward potassium currents could be identified: a
      transient 4-aminopyridine-sensitive current (Ia) and a persistent outward current
      sensitive to tetraethylammonium (Id). Ia activated at -40 mV, and steady-state
      activation and inactivation midpoints were -16 and -74 mV, respectively. Decay
      time constants ranged from 7 ms at -30 mV to 19 ms at +80 mV. Id activated at -30
      mV. A third K+ current sensitive to cesium activated with hyperpolarizing command
      voltages and showed strong inward rectification. Transient, voltage-activated
      sodium currents (I(Na)) were tetrodotoxin sensitive (100 nM) and activated at
      about -40 mV, peaked at about -10 mV, and reversed at +63 mV. I(Na) was half
      inactivated at -49 mV and half-activated at -19 mV. During the first 2 wk of
      postnatal development, the percentage of cells showing inwardly rectifying K+
      current (Ir), Ia, and I(Na) increased significantly from 40% (at P5) to 90% (at
      P20-P50). By contrast, almost all cells independent of age expressed Id. Specific
      conductances for Ir (g(ir)) and Ia increased significantly between P5 and P20,
      concomitant with a decrease in input resistance. By contrast, specific
      conductance of the outwardly rectifying K+ current (g(d)) decreased threefold
      between P5 and P20. Specific Na+ conductance was always <1/4 of the total
      potassium conductance. These results indicate that CA1 hippocampal astrocytes are
      characterized by expression of voltage-activated Na+ channels and three types of
      K+ channels showing changes in their relative expression during early postnatal
      development: 1) the number of cells expressing Ia, Ir, and I(Na) increases
      significantly and 2) their specific conductance changes such that g(d),
      predominant at P5-P20, is gradually replaced by g(ir), the predominant
      conductance in adult astrocytes. Adult morphological and electrophysiological
      phenotypes are established at about P20. These data suggest that previous studies
      in which cultured or acutely isolated cells from immature or embryonic rats were
      used were not adequately reflecting the properties of hippocampal astrocytes in
      situ.

PMID- 9242295
TI  - Relationship of cerebellar Purkinje cell simple spike discharge to movement
      kinematics in the monkey.
AB  - The simple spike discharge of 231 cerebellar Purkinje cells in ipsilateral
      lobules V and VI was recorded in three monkeys trained to perform a visually
      guided reaching task requiring movements of different directions and distances.
      The discharge of 179 cells was significantly modulated during movement to one or
      more targets. Mean simple spike rate was fitted to a cosine function for
      direction tuning, a simple linear function for distance modulation, and a
      multiple linear regression model that included terms for direction, distance, and
      target position. On the basis of the fit to the direction and distance models,
      there were more distance-related than direction-related Purkinje cells. The
      simple spike discharge of most direction-related cells modulated at only one
      target distance. The preferred directions for the simple spike tuning were not
      uniformly distributed across the workspace. The discharge of most distance
      related cells modulated along only one movement direction. On the basis of the
      multiple linear regression model, simple spike discharge was also correlated with
      target position, in addition to direction and distance. Approximately half of the
      Purkinje cells had simple spike activity associated with only a single parameter,
      and only a small fraction of the cells with all three. The multiple regression
      model was extended to evaluate the correlations as a function of time.
      Considerable overlap occurred in the timing of the simple spike correlations with
      the parameters. The latency for correlation with movement direction occurred
      mainly in a 500-ms interval centered on movement onset. The correlations with
      target position also occurred around movement onset, in the range of -200-500 ms.
      Distance correlations were more variable, with onset latencies from -500 to 1,000
      ms. These results demonstrate that the simple spike discharge of cerebellar
      Purkinje cells is correlated with movement direction, distance, and target
      position. Comparing these results to motor cortical discharge shows that the
      correlations with these parameters were weaker in Purkinje cell simple spike
      discharge, and that, for the majority of Purkinje cells, the simple spike
      discharge was significantly related to only a single movement parameter. Other
      differences between simple spike responses and those of motor cortical cells
      include the nonuniform distribution of preferred directions and the extensive
      overlap in the timing of the correlations. These differences suggest that
      Purkinje cells process, encode, and use kinematic information differently than
      motor cortical neurons.

PMID- 9242296
TI  - Tensile and compressive responses of nociceptors in rat hairy skin.
AB  - Mechanically sensitive nociceptor afferents were studied in a preparation of
      isolated skin from rat leg. Each neuron was studied while the skin was subjected
      to tensile and compressive loading. The experiment was designed to create highly
      uniform states of stress in both tension and compression. Tensile loads were
      applied by pulling on the edges of the sample. Applied loads were used to
      determine the tensile stresses. Surface displacements were used to determine
      tensile strains. Compressive loads were applied by indenting the surface of the
      skin with flat indenter tips applied under force control. The skin was supported
      by a flat, hard substrate. Compressive stresses were determined from the applied
      loads and tip geometry. Compressive strains were determined from skin thickness
      and tip excursions. All nociceptors were activated by both tensile and
      compressive loading. There was no interaction between the responses to
      compressive and tensile stimuli (i.e., the responses were simply additive).
      Responses of nociceptors were better related to tensile and compressive stresses
      than to strains. Nociceptors responded better to tensile loading than to
      compressive loading. Response thresholds were lower and sensitivities were higher
      for tensile stress than for compressive stress. The response to compression was
      better related to compressive stress than to other stimulus parameters (i.e.,
      load/circumference or simply load). Indentations of intact skin over a soft
      substrate such as muscle would be expected to cause widespread activation of
      nociceptors because of tensile stresses.

PMID- 9242298
TI  - Neurons sensitive to interaural temporal disparities in the medial part of the
      ventral nucleus of the lateral lemniscus.
AB  - The ventral nucleus of the lateral lemniscus (VNLL) is implicated in processing
      monaural sounds, because its neurons receive input chiefly from the contralateral
      cochlear nucleus. However, we demonstrate here that a region of the VNLL contains
      a distinct population of neurons that process binaural sounds and are sensitive
      to interaural temporal disparities (ITDs). Responses of single neurons were
      recorded from unanesthetized rabbits by using metal electrodes or micropipettes
      loaded with dextran tagged with either biotin or a fluorescent label.
      Reconstructions of recording sites based on a few marks indicated that ITD
      sensitive neurons were located in a medial region of VNLL that has a low density
      of neurons or in the adjacent reticular formation. In one animal the locations of
      five ITD-sensitive neurons were marked directly by injection of dextrans with
      different tags. All of these neurons lay in the medial region of the VNLL. The
      ITD-sensitive neurons of the VNLL had characteristic responses. Most neurons
      responded only at the onset of contralaterally or binaurally presented tones;
      many did not respond to ipsilateral stimulation alone and did not follow dynamic
      changes in the ITD. The presence of ITD-sensitive neurons in the VNLL that
      responded only at the onset of tones suggests that this center plays a role in
      the localization of transient sounds.

PMID- 9242297
TI  - Nonlinear processing of tactile information in the thalamocortical loop.
AB  - Rats explore tangible objects in a manner such that, at any given moment in time,
      multiple facial whiskers simultaneously contact the surface of the object.
      Although both thalamic and cortical neurons responsible for processing such
      tactile information have large, multiwhisker receptive fields, it remains unclear
      what kinds of computations can be carried out by these neuronal populations when
      behaviorally relevant multiwhisker stimuli are used. By simultaneously recording
      the activity of up to 78 cortical and thalamic neurons per animal, we observed
      that the magnitude of sensory responses and the spatial spread of ensemble
      activity increased in a nonlinear fashion according to the extent and spatial
      orientation of the multiwhisker stimuli. Supralinear responses were seen more
      frequently with vertically than with horizontally oriented stimuli. These data
      suggest that thalamocortical interactions in the rat somatosensory system can
      generate complex spatial transformations of multiwhisker stimuli that go beyond
      the classic inhibitory interactions previously observed.

PMID- 9242299
TI  - Graded effects of spatial and featural attention on human area MT and associated
      motion processing areas.
AB  - Functional magnetic resonance imaging was used to quantify the effects of changes
      in spatial and featural attention on brain activity in the middle temporal visual
      area and associated motion processing regions (hMT+) of normal human subjects.
      When subjects performed a discrimination task that directed their spatial
      attention to a peripherally presented annulus and their featural attention to the
      speed of points in the annulus, activity in hMT+ was maximal. If subjects were
      instead asked to discriminate the color of points in the annulus, the magnitude
      and volume of activation in hMT+ fell to 64 and 35%, respectively, of the
      previously observed maximum response. In another experiment, subjects were asked
      to direct their spatial attention away from the annulus toward the fixation point
      to detect a subtle change in luminance. The response magnitude and volume dropped
      to 40 and 9% of maximum. These experiments demonstrate that both spatial and
      featural attention modulate hMT+ and that their effects can work in concert to
      modulate cortical activity. The high degree of modulation by attention suggests
      that an understanding of the stimulus-driven properties of visual cortex needs to
      be complemented with an investigation of the effects of task-related factors on
      visual processing.

PMID- 9242301
TI  - Long-term synaptic plasticity in the honeybee.
AB  - A monosynaptic response was recorded in vivo in the mushroom body of the bee
      brain, an important site for memory consolidation. Focal electrical stimulation
      of a major afferent input evoked an extracellular field potential that consisted
      of a presynaptic fiber volley and a postsynaptic response. We report a long
      lasting potentiation of the synaptic response (2.6-fold increase; < or = 3.5 h).
      Potentiation of the response was induced by low-frequency stimulation (0.02-1.0
      Hz), was input specific, and was maintained in the absence of stimulation. Paired
      pulse facilitation of the response was converted to paired-pulse depression after
      potentiation, suggesting a presynaptic mechanism. This is the first demonstration
      of long-term synaptic plasticity in the insect brain.

PMID- 9242300
TI  - Nucleus gracilis: an integrator for visceral and somatic information.
AB  - The nucleus gracilis (NG) receives an abundance of visceral input from various
      abdominal organs and is proposed to play an important role in visceral pain
      processing. The purpose of this study was to investigate the necessity of the NG
      for colorectal input into the ventral posterolateral (VPL) nucleus of the
      thalamus. Single-cell recordings were made from nine VPL cells isolated in nine
      different male Sprague Dawley rats anesthetized with pentobarbital sodium.
      Responses of the VPL cells to colorectal distension (CRD) and to cutaneous
      stimuli were obtained before and after lesioning of the NG. Electrolytic (n = 5)
      and chemical (n = 4) lesions of the NG were made in different preparations. The
      chemical lesions were made by injecting a solution of kainic acid into the NG.
      Kainic acid presumably kills neuronal cell bodies and spares axons of passage.
      The results indicate that a lesion of the NG, regardless of its type, reduces
      dramatically the responses of VPL neurons to innocuous cutaneous stimuli, and, to
      a lesser extent, the responses to CRD. Attenuation of VPL neuronal responses to
      CRD as well as to innocuous cutaneous stimuli by the NG lesions emphasizes the
      role of the dorsal column in visceral nociception and suggests that the NG is an
      integration center for visceral and cutaneous information flowing into the VPL
      nucleus.

PMID- 9242302
TI  - Local feedback signals are not distorted by prior eye movements: evidence from
      visually evoked double saccades.
AB  - Recent experiments have shown that the amplitude and direction of saccades evoked
      by microstimulation of the monkey superior colliculus depend systematically on
      the amplitude and direction of preceding visually guided saccades as well as on
      the postsaccade stimulation interval. The data are consistent with the hypothesis
      that an eye displacement integrator in the local feedback loop of the saccadic
      burst generator is gradually reset with a time constant of approximately 45 ms.
      If this is true, similar effects should occur during naturally evoked saccade
      sequences, causing systematic interval-dependent errors. To test this prediction
      in humans, saccades toward visual single- and double-step stimuli were elicited,
      and the properties of the second saccades were investigated as a function of the
      intersaccadic interval (ISI). In 15-20% of the saccadic responses, ISIs fell well
      below 100 ms. The errors of the second saccades were not systematically affected
      by the preceding primary saccade, irrespective of the ISI. Only a slight increase
      in the endpoint variability of second saccades was observed for the shortest
      ISIs. These results are at odds with the hypothesis that the putative eye
      displacement integrator has a reset time constant >10 ms. Instead, it is
      concluded that the signals involved in the internal feedback control of the
      saccadic burst generator reflect eye position and/or eye displacement accurately,
      irrespective of preceding eye movements.

PMID- 9242303
TI  - Role of group I metabotropic glutamate receptors in the patterning of
      epileptiform activities in vitro.
AB  - In guinea pig hippocampal slices, picrotoxin elicited spontaneous epileptiform
      bursts 300-550 ms in duration. Additional application of (R,S)-3,5
      dihydroxyphenylglycine or (S)-3-hydroxyphenylglycine, agonists specific for group
      I metabotropic glutamate receptors (mGluRs), or (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid, a broad-spectrum mGluR agonist, converted picrotoxin-induced
      interictal bursts into prolonged discharges measured on the order of seconds. The
      prolonged discharges induced by selective group I mGluR agonist continued to be
      produced for hours after agonist removal. The antagonists (S)-4
      carboxyphenylglycine and (+)-alpha-methyl-4-carboxyphenylglycine had no effect on
      the duration of picrotoxin-induced interictal bursts. However, after agonist
      exposure, the persistent prolonged discharges occurring in the absence of agonist
      were reversibly suppressed by the antagonists, suggesting that the activity is
      maintained via endogenous activation of group I mGluRs by synaptically released
      glutamate. Our results suggest that, under some conditions, activation of group I
      mGluRs produces long-lasting enhancement of synaptic responses, mediated at least
      in part by autopotentiation of the group I mGluR response itself, which may
      result in the production of seizure discharges and contribute to epileptogenesis.

PMID- 9242304
TI  - Psychophysical properties of the trunk midline.
AB  - This study was carry out to obtain direct evidence that the body midline actually
      is perceived and to assess some psychophysical properties of this line. Twelve
      normal, right-handed male subjects were asked to make accurate pointing movements
      toward the midline of the anterior trunk on the basis of their mental
      representation of this line. Each hand was used to point while the head was
      either aligned with the trunk or tilted 30 degrees to the right or left. Analysis
      of end-positions of pointing on trunk images acquired by an image analysis system
      indicated that the trunk midline indeed is perceived as a straight line. Three
      putative trunk midlines were taken into consideration on the basis of anatomic
      landmarks, and it was found that the mental representation of the trunk midline
      came nearest to the line orthogonal to the intermammary line crossing its
      midpoint. The performing hand and the position of the head relative to the trunk
      both had an effect on the mental representation of the trunk midline. These
      findings suggest that somatosensory signals from the trunk, as well as
      proprioceptive input from the neck, contribute to the elaboration of the
      subject's mental representation of the trunk midline.

PMID- 9242305
TI  - GABA(B)-receptor-mediated inhibition in developing mouse ventral posterior
      thalamic nucleus.
AB  - Inhibitory postsynaptic potentials (IPSPs) generated by activation of the
      thalamic reticular nucleus (RTN) were recorded in neurons of the ventral
      posterior nucleus (VP) in vitro in slices from mice aged postnatal day (P)1-P17.
      An early IPSP peaking 41 +/- 2.5 (SE) ms after electrical stimulation of the
      internal capsule or RTN was found in 96% of VP neurons. This early IPSP was
      blocked by bicuculline, showing its dependence on gamma-aminobutyric acid-A
      (GABA(A)) receptors. A late IPSP peaking 357 +/- 27 ms after the stimulus was
      observed in 22% of VP neurons in control medium but was uncovered in 38% of
      neurons when bicuculline was added. The late IPSP was blocked by addition of a
      GABA(B) antagonist, 2-hydroxysaclofen, to the medium (n = 7); it had a reversal
      potential of -98 +/- 1.3 mV, 14 mV negative to the early component. In contrast
      to the early IPSP, whose reversal potential became more negative during postnatal
      development, the reversal potential of the late IPSP remained constant throughout
      the postnatal period studied. The most significant change in the late IPSP was
      shortening in duration, with reduction in latency-to-peak by >400 ms, between P1
      and P10. No changes of comparable magnitude were observed in the duration of the
      earlier GABA(A) response. These results show that both GABA(A) and GABA(B) IPSPs
      are present very early in the postnatal thalamus and that their characteristics
      evolve along independent paths during postnatal development.

PMID- 9242306
TI  - The motor system does not learn the dynamics of the arm by rote memorization of
      past experience.
AB  - The purpose of this study was to investigate the learning mechanisms underlying
      motor adaptation of arm movements to externally applied perturbing forces. We
      considered two alternative hypotheses. According to one, adaptation occurs
      through the learning of a mapping between the states (positions and velocities)
      visited by the arm and the forces experienced at those states. The alternative
      hypothesis is that adaptation occurs through the memorization of the temporal
      sequence of forces experienced along specific trajectories. The first mechanism
      corresponds to developing a model of the dynamics of the environment, whereas the
      second is a form of "rote learning." Both types of learning would lead to the
      recovery of the unperturbed performance. We have tested these hypotheses by
      examining how adaptation is transferred across different types of movements. Our
      results indicate that 1) adaptation to an externally applied force field occurs
      with different classes of movements including but not limited to reaching
      movements and 2) adaptation generalizes across different movements that visit the
      same regions of the external field. These findings are not compatible with the
      hypothesis of rote learning. Instead, they are consistent with the hypothesis
      that adaptation to changes in movement dynamics is achieved by a module that
      learns to reproduce the structure of the environmental field as an association
      between visited states and experienced forces, independent of the kinematics of
      the movements made during adaptation.

PMID- 9242307
TI  - Adrenoceptor-mediated elevation of ambient GABA levels activates presynaptic
      GABA(B) receptors in rat sensorimotor cortex.
AB  - At inhibitory synapses in the mature neocortex and hippocampus in vitro,
      spontaneous action-potential-dependent and -independent release of gamma
      aminobutyric acid (GABA) activates postsynaptic GABA(A) receptors but not pre- or
      postsynaptic GABA(B) receptors. Elevation of synaptic GABA levels with
      pharmacological agents or electrical stimulation can cause activation of GABA(B)
      receptors, but the physiological conditions under which such activation occurs
      need further elucidation. In rodent sensorimotor cortex, epinephrine produced a
      depression in the amplitude of evoked monosynaptic inhibitory postsynaptic
      currents (IPSCs) and a concomitant, adrenoceptor-mediated increase in the
      frequency of spontaneous IPSCs. Blockade of GABA(B) receptors prevented the
      depression of evoked IPSC amplitude by epinephrine but did not affect the
      increase in spontaneous IPSC frequency. These data show that adrenoceptor
      mediated increases in spontaneous IPSCs can cause activation of presynaptic
      GABA(B) receptors and indirectly modulate impulse-related GABA release,
      presumably through elevation of synaptic GABA levels.

PMID- 9242308
TI  - Neuronal activity in the ventral part of premotor cortex during target-reach
      movement is modulated by direction of gaze.
AB  - We recorded 200 neurons from the ventral part of the premotor cortex (PMv) and
      110 neurons from the primary motor cortex (MI) of a monkey performing a visually
      cued arm-reaching task with a delay. We compared neuronal activity in the
      premovement period while the monkey reached the target with the eyes fixating on
      either a left or right fixation target. Our data demonstrate that about half of
      the movement-related activity in the PMv was modulated by the direction of gaze.
      In contrast, a vast majority of the activity of MI neurons and about half of PMv
      neurons were not influenced by the direction of gaze. We further analyzed the
      movement-related activity during the reaching movement to targets at the top,
      bottom, left, and right of each fixation point. The magnitude of activity of
      neurons showing the gaze-direction selectivity was primarily determined by the
      position of the reaching target relative to the eye-fixation target, and not by
      the position of the target relative to the animal's body. These data suggest that
      a part of the coordinate transformation of the motor command signals concerning
      the direction of reaching from the retinotopic to body-centered frame of
      reference may occur at the level of premotor cortex but not in MI.

PMID- 9242309
TI  - Detection and characterization of autoantibodies directed against neurofilament
      proteins in human African trypanosomiasis.
AB  - In serum and in cerebrospinal fluid (CSF) from patients with human African
      trypanosomiasis (HAT) with central nervous system involvement, we detected
      autoantibodies directed to some proteins from these tissues. The characterization
      of antigenic proteins by Western blotting showed that the antibodies recognized
      the 200-kD and 160-kD proteins of neurofilament (NF). Serum anti-NF antibodies
      were more frequent in HAT patients than in control subjects (86% versus 24%; P <
      10[-9]) and they belonged predominantly to the IgM class (anti-NF IgM = 86%
      versus anti-NF IgG = 4%; P < 10[-9]) in the patients with stage II (central
      nervous system involvement) HAT. The CSF antibodies to NF were IgM in 88% (22 of
      25) of the cases and IgG in 32% (8 of 25) of the cases. Epitopes shared by NF and
      trypanosomes were detected by indirect immunofluorescence and this was confirmed
      by the disappearance of anti-NF reactivity after adsorption with trypanosome
      antigens (Trypanosoma brucei brucei or T. b. gambiense). Anti-NF antibodies were
      undetectable in the CSF from stage I HAT patients.

PMID- 9242310
TI  - Bacteriologic studies of skin, tissue fluid, lymph, and lymph nodes in patients
      with filarial lymphedema.
AB  - Filarial lymphedema is complicated by frequent episodes of
      dermatolymphangioadenitis (DLA). It is not certain whether DLA is of filarial or
      bacterial etiology. The frequency of episodic DLA does not depend on the presence
      or absence of microfilariae. Antibiotic therapy is effective in prevention and
      treatment of DLA. These observations point to the bacterial rather than filarial
      etiology of DLA. Skin and lymph node biopsies, tissue fluid, lymph, and blood
      from patients with chronic filarial lymphedema, and during acute episodes of DLA,
      were cultured for detection of bacteria. A high prevalence of bacterial isolates
      from the tissue fluid (64%), lymph (75%), and inguinal lymph nodes (66%) of limbs
      with filarial lymphedema was found. Bacillus cereus, Staphylococcus epidermidis,
      S. hominis, S. capitis, S. xylosus, and Micrococcus spp. were the most common
      isolates. Bacteria were also isolated from the blood of patients with recent
      episodes of DLA, with strains of the same phenotype and antibiotic sensitivity in
      all specimens from patients with DLA. Bacterial strains of the same phenotype and
      antibiotic sensitivity were documented on the toe web surface and in tissue fluid
      (25%), lymph (26%), or lymph nodes (41%). Increasing prevalence of bacterial
      isolates in tissue fluid, lymph, and lymph nodes was observed in advanced stages
      of lymphedema. Bacilli and cocci were sensitive to gentamicin, tetracyline,
      rifampicin, vancomycin, kanamycin and cotrimoxazole, and least sensitive to
      penicillin. Blood cultures of patients in the periods between DLA attacks were
      negative. In healthy controls without edema and episodes of DLA, tissue fluid did
      not contain bacteria. In lymph, only single colonies of Micrococcus and
      Acinetobacter were cultured in 12% of the cases. Impaired lymph drainage and lack
      of elimination of penetrating bacteria may be responsible for progression of
      lymphedema and recurrent attacks of DLA.

PMID- 9242311
TI  - Evaluation of an ultrasonographic score for urinary bladder morbidity in
      Schistosoma haematobium infection.
AB  - An ultrasonographic urinary bladder morbidity score was developed and tested in
      510 patients with schistosomiasis haematobia, and then evaluated for screening
      1,134 randomly selected children from villages endemic for Schistosoma
      haematobium. The ultrasonographic urinary bladder morbidity score had four grades
      ranging from normal to marked thickening of the urinary bladder wall or any
      polyps or masses. Among both patients and randomly screened subjects, the
      ultrasonographic score was greater (P = 0.01 and P < 0.01) in males than in
      females. Children examined in the clinic had higher (P = 0.03) ultrasonographic
      scores than adults. Infected subjects in communities were more likely (P < 0.001)
      to have urinary bladder morbidity than uninfected subjects, and clinic patients
      with egg counts > or = 20 eggs/10 ml of urine had higher (P = 0.03)
      ultrasonographic urinary bladder morbidity scores than those with lighter
      infections. The geometric mean egg count was higher (P = 0.04) in clinic patients
      with grade II and III lesions than in those with grade 0 and I lesions. There was
      progressive improvement of the grade of urinary bladder morbidity scores in
      patients treated with praziquantel at each follow-up examination (P < 0.001) and
      there was a positive relationship (P < 0.01) between urinary bladder morbidity
      scores and ultrasonographic-detected renal back pressure changes. The
      ultrasonographic urinary bladder morbidity score objectively measured the
      severity of urinary bladder morbidity and correlated with intensity of S.
      haematobium infection in our subjects. It can be used in evaluating both
      morbidity in patients and in community surveys and in following the outcome of
      chemotherapy.

PMID- 9242312
TI  - Predictors of a fatal outcome following childhood cerebral malaria.
AB  - Despite prompt treatment with an effective anti-malarial drug, cerebral malaria
      still has a mortality of 20-30%. To identify factors that may contribute to this
      high fatality rate, we have studied the relationship between clinical and
      laboratory features and a fatal outcome in 624 Gambian children with strictly
      defined cerebral malaria. One hundred twenty-four children (21.5%) died. Three
      quarters of the deaths occurred within 24 hr of admission. Multiple logistic
      regression analysis showed that a cold periphery (odds ratio [OR] = 2.7), a deep
      coma (OR = 2.0), and hypoglycemia (OR = 4.1) were the clinical signs and
      laboratory parameters that predicted death most strongly. More than 90% of the
      children who died had at least one of these conditions. Also, children with
      elevated urea levels on admission or those who experienced multiple episodes of
      hypoglycemia or multiple convulsions subsequently were more likely to die. A
      combination of clinical and laboratory abnormalities can identify a group of
      children with cerebral malaria who are most at risk of dying, who require
      intensive care and who are candidates for new forms of therapy.

PMID- 9242314
TI  - Stability of essential drugs in the field: results of a study conducted over a
      two-year period in Burkina Faso.
AB  - To evaluate the stability of essential drugs stored in realistic tropical
      conditions, we have carried out a two-year prospective study in western Burkina
      Faso. Twenty-seven essential drugs were stored in a rural site and a urban one
      where temperature and hygrometry were recorded daily. Samples of each drug were
      taken for further analysis to the World Health Organization Collaborative Center
      for the Study of Stability of Drugs in Nantes, France every three months.
      Quantitative analysis showed that the majority of samples suffered no significant
      loss of their active ingredient. In contrast, ampicillin, erythromycin,
      sulfaguanidine, injectable furosemide, penicillin G, trimethoprim, and
      chloroquine showed more than a 10% quantitative loss of their active ingredient.
      Thus, it is not recommended that these essential drugs be stored for more than
      one year in a tropical climate.

PMID- 9242313
TI  - Failure of mebendazole in treatment of human hookworm infections in the southern
      region of Mali.
AB  - Preliminary studies indicated that single-dose (500 mg) mebendazole gave
      disappointing results in the treatment of hookworm infections (Necator
      americanus) in Mali. A placebo-controlled, randomized trial conducted with the
      participation of 103 infected subjects (background hookworm prevalence > 50%)
      confirmed that mebendazole (Vermox) did not reduce parasite burdens
      significantly, as assessed through fecal egg counts. In contrast, a group of
      subjects treated with pyrantel (Combantrin) experienced a significant reduction
      in fecal worm egg counts (overall, both sexes combined showed a 75% reduction).
      Male subjects carried significantly more intense infections compared with
      females, but there was no gender difference in response to treatment. A standard
      egg hatch assay showed that N. americanus from our subjects in Mali was more
      resistant to benzimidazoles compared with a laboratory-maintained strain that had
      not been exposed to anthelmintics in more than 100 generations (50% effective
      dose = 0.12 and 0.07 microg/ml of thiabendazole, respectively), suggesting that,
      among other possibilities, the development of resistance to the benzimidazoles by
      N. americanus may have contributed to the drug failure. Whatever the underlying
      explanation, our results indicate that single-dose treatment with mebendazole is
      an ineffective treatment for hookworm infections and despite its relatively cheap
      cost and wide availability, mebendazole should not be considered a drug of choice
      in the mass treatment of hookworm infections in this region of Mali.

PMID- 9242315
TI  - Age distribution of lymphocytic choriomeningitis virus serum antibody in
      Birmingham, Alabama: evidence of a decreased risk of infection.
AB  - Lymphocytic choriomeningitis virus (LCMV) is an arenavirus that causes human
      disease ranging from a mild, flu-like illness to meningitis. Infections occur
      principally in and around the home due to contact with infected mice. Data on the
      incidence of LCMV infection in the United States are scarce but suggest that the
      risk of infection may have decreased over the past 30-40 years. To examine this
      hypothesis, sera from an age-stratified sample of hospital patients in
      Birmingham, Alabama were tested for LCMV antibody by ELISA. The overall
      prevalence of LCMV-specific IgG was 3.5% (56 of 1,600). The prevalence of
      antibody among those < 30 years of age was 0.3% (2 of 600), while the prevalence
      among those 30 years of age and older was 5.4% (P < 0.0001). Multiple logistic
      regression was used to identify risk factors for LCMV seropositivity. Age was
      positively associated (P < 0.0001) and socioeconomic status was negatively
      associated with a positive antibody test result (P < 0.03). These data are
      consistent with a decreased incidence of human LCMV infection in Birmingham over
      the past 30-40 years.

PMID- 9242316
TI  - Vector competence of select black fly species for vesicular stomatitis virus (New
      Jersey serotype).
AB  - Black flies collected from southern Arizona were evaluated for their vector
      competence to the Oaxaca and Camp Verde isolates of vesicular stomatitis virus
      (New Jersey serotype) (VSV-NJ). The Camp Verde isolate is the index isolate of
      the 1982-1983 VSV-NJ epizootic that infected humans and livestock in 14 western
      states. Previous experiments have shown that colonized Simulium vittatum females
      are competent laboratory vectors of both virus isolates. However, under
      controlled laboratory conditions, Simulium bivittatum and S. longithallum were
      found to be incompetent vectors of both virus isolates. After oral infections,
      the Oaxaca isolate replicated in 35% and 38% of S. bivittatum and S.
      longithallum, respectively, but did not disseminate to the salivary glands. Thus,
      virus was not detected in the saliva of either black fly species with either VSV
      NJ isolate, indicating the presence of a midgut barrier. Simulium notatum was
      found to be a competent laboratory vector of both virus isolates. Infectious
      virions were detected in the saliva of 23% and 26% of S. notatum infected orally
      with the Oaxaca and Camp Verde VSV-NJ isolates, respectively. This study suggests
      that the black fly identified as S. bivittatum was probably not involved in virus
      dissemination during the 1982-1983 epizootic in the western United States.
      Because the geographic distribution of S. notatum is not known, its involvement
      in that epizootic remains obscure.

PMID- 9242318
TI  - Human T cell lymphotropic virus type-1-associated myelopathy/tropical spastic
      paraparesis in Sao Paulo, Brazil: association with blood transfusion.
AB  - Human T cell lymphotropic virus type-1 (HTLV-1) associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) has been epidemiologically linked to prior blood
      transfusion. The prevalence of transfusion as a risk factor for infection varies
      among endemic areas. Here we report the relative frequency of reported history of
      blood transfusion among 52 patients evaluated in Sao Paulo, Brazil. A patient
      reported history of blood transfusion prior to the onset of symptoms, found in 15
      (28.8%) of the patients, was the most important risk factor identified in this
      group of patients when compared with a history of sexually transmitted diseases,
      homo/bisexuality, sexual promiscuity (three or more sexual partners a year), and
      intravenous drug use. The mean time between reported transfusions and the onset
      of symptoms was longer than previously reported. There was no trend toward a more
      severe evolution to motor inability among the HAM/TSP patients with a history of
      previous transfusion.

PMID- 9242317
TI  - The first reported outbreak of dengue hemorrhagic fever in Irian Jaya, Indonesia.
AB  - During the months of September 1993 through February 1994, an outbreak of
      hemorrhagic fever occurred in the city of Jayapura, the provincial capital of
      Irian Jaya, Indonesia. Seventy-two patients (age range = 1-41 years) with
      suspected dengue hemorrhagic fever (DHF) were enrolled into the outbreak
      investigation conducted during October-November 1993. The pediatric patient
      population consisted of 36 individuals ages 1-12 years of age with a similar male
      to female ratio. From clinical histories obtained from the children diagnosed
      with DHF (n = 23), the predominant complaints were fever (100%), headache
      (96.7%), vomiting (47.8%), abdominal pain (39.1%), back/bone pain (39.1%), cough
      (39.1%), sore throat (21.7%), convulsions (17.4%), and eye pain (13.0%). Clinical
      findings of the same pediatric patients included a positive tourniquet test
      result (100%), thrombocytopenia (100%), hemoconcentration (100%), skin petechiae
      (43.5%), epistaxis (39.1%), and maculopapular rash (26%). All four of the
      children diagnosed with DHF grade IV had hepatomegaly, pleural effusion, ascites,
      cold perspiration, and confusion. Serologic data demonstrated that a majority (46
      of 70, 68.7%) of the individuals assessed did not have significant levels of IgM
      specific for dengue viruses at the time of their admission. However, the nine
      successful dengue virus isolations were only from these serononreactive cases
      (19.6%). From the other patients assessed, 11.4% had a primary (or first
      exposure) serologic response to dengue virus antigen (predominantly IgM); 17.1%
      had a secondary (or subsequent exposure) serologic response to the same dengue
      antigens (predominantly IgG response) and 5.7% (four adults) had indeterminate
      serologic data that could not differentiate between reactivity to dengue or
      Japanese encephalitis virus antigen preparations. Virus culture of blood samples
      produced nine dengue virus isolates: DEN- 1 (2), DEN-2 (1), and DEN-3 (6).
      Japanese encephalitis and influenza viruses were not isolated from blood and
      pharyngeal specimens, respectively, from any of the patients. Thus, this first
      reported outbreak of DHF in Irian Jaya, Indonesia was found to be attributed to
      dengue viruses types 1, 2, and 3.

PMID- 9242319
TI  - Prevalence of hepatitis E virus IgG antibodies in patients from a referral unit
      of liver diseases in Salvador, Bahia, Brazil.
AB  - Hepatitis E virus (HEV) is prevalent in Asia and Africa. Recently, it was also
      described in Mexico, but epidemiologic data from other Latin American countries
      are scarce. The seroprevalence of anti-HEV in a referral hepatology unit in
      northern Brazil was determined by testing for anti-HEV IgG in 701 serum samples
      from our serum bank. Specimens analyzed were from 200 blood donors, 79 patients
      with acute viral hepatitis (AVH), 392 hemodialyzed patients, and 30 carriers of
      schistosomiasis. Duplicate test results for anti-HEV were positive in four (2%)
      of 200 of the blood donors, three (10%) of the 30 carriers of schistosomiasis,
      and in none of the 392 hemodialyzed patients. Fourteen (17.7%) of the AVH
      patients were positive, as were six (25%) of 24 with hepatitis A virus, three
      (11%) of 26 with hepatitis B virus, 0 (0%) of 12 with hepatitis C virus, and five
      (29%) of 17 with non-A, non-B, non-C hepatitis viruses. Among AVH cases, those
      with hepatitis A virus had a higher frequency of anti-HEV positivity compared
      with all other hepatotropic viruses (P < 0.0003). We conclude that HEV is
      prevalent in northern Brazil. The higher prevalence in patients compared with
      blood donors could be explained by the lower social condition of patients who
      sought public health service in this area, in contrast with the heterogeneous
      socioeconomic distribution of blood donors. Patients with AVH due to hepatitis A
      had a greater frequency of anti-HEV, probably because of similar routes of
      transmission for both hepatitis A and E viruses. Finally, the absence of anti-HEV
      in the hemodialyzed group could be explained by a lower immunologic response
      found in patients with chronic renal failure.

PMID- 9242320
TI  - Epidemic and sporadic hepatitis E virus transmission in West Kalimantan (Borneo),
      Indonesia.
AB  - A cross-sectional survey was conducted in West Kalimantan (Borneo), Indonesia to
      geographically profile hepatitis E virus (HEV) prevalence in the riverine areas
      recognized as the foci of epidemic HEV transmission in 1987. Additionally, a
      contiguous, although distinct, population with no identifiable historical
      exposure to epidemic HEV was surveyed downstream for comparative purposes. Eight
      hundred eighty-five sera were assayed by enzyme immunoabsorbent assay for anti
      HEV IgG and anti-hepatitis A virus (HAV) IgG markers. A very high percent (90%)
      of both the outbreak and comparison populations was anti-HAV IgG positive by the
      age of nine years. In contrast, the prevalence of anti-HEV IgG in the outbreak
      area (50%) was significantly higher than in the comparison area (23%) (P <
      0.0001). In both the outbreak and comparison areas, anti-HEV IgG prevalence
      increased with age ( < 0.0001), except for the group > or = 50 years of age. The
      prevalence (53%) of antibody to HEV in the population > or = seven years of age
      from the outbreak area (alive during the actual 1987 outbreak) was significantly
      (P < 0.0001) greater than among the children < seven years of age (born after the
      outbreak) (15%). However, anti-HEV IgG prevalence among the population from the
      comparison area did not differ significantly between the > or = seven- (23%) and
      < seven- (20%) year-old age groups. The percentage of anti-HEV IgG-positive
      individuals among males (47%) from the outbreak area was lower (P < 0.05)
      compared with females (55%). While overall usage of river water for drinking
      purposes was not universal, dependence on river water as a primary source was
      significantly higher (P < 0.001) in households from the outbreak area (60%)
      compared with the comparison area (30%). This study indicates persistence of an
      anti-HEV IgG response in a large percentage of the population seven years after
      an epidemic of HEV infections. Also, the relatively high prevalence (15%) of anti
      HEV in children < seven years of age from the outbreak area reflects continuing,
      sporadic infections.

PMID- 9242322
TI  - Differentiation of Entamoeba histolytica and Entamoeba dispar from German
      travelers and residents of endemic areas.
AB  - Entamoeba histolytica and E. dispar detected in fecal samples of German travelers
      and residents of tropical and subtropical countries were cultured and
      differentiated by the polymerase chain reaction (PCR) and hexokinase isoenzyme
      typing. Twenty-one of 60 isolates were identified as E. histolytica. It was shown
      that 13 of 18 German short-term travelers were infected with E. histolytica,
      whereas only three of 22 of the examined inhabitants of tropical countries and
      five of 20 German long-term travelers harbored E. histolytica. It appears that
      short-term travelers represent a high risk group for infection with the pathogen
      E. histolytica.

PMID- 9242321
TI  - High prevalence of hepatitis C infection among blood donors in northeastern
      Thailand.
AB  - Previous studies on the prevalence of hepatitis C virus (HCV) infection in Asian
      countries reported an average prevalence of less than 1.5%. In this study a
      combination of second- and third-generation enzyme immunoassays (EIAs),
      immunoblot analysis, and polymerase chain reaction was used to evaluate the
      prevalence of HCV infection in 3,255 volunteer blood donors in northeastern
      Thailand. Antibodies to HCV were detected in 6.5% of male blood donors and 0.9%
      of female blood donors, giving an overall prevalence of 5.6% in this population
      (gender-adjusted prevalence of 3.7%). The prevalence was higher in males than in
      females (P < 0.0001) and increased with age, reaching a peak at 31-40 years of
      age. More than 90% of the EIA-positive samples tested positive by immunoblot
      analysis, giving an estimated minimal prevalence of antibodies to HCV in the
      blood donors of 5.2%. Approximately 80% of the EIA-positive blood donors were
      viremic as determined by the presence of HCV RNA detected by the polymerase chain
      reaction, indicating that at least 4.5% of volunteer blood donors had detectable
      HCV RNA and were considered potentially infectious. The prevalence of HCV
      infection in this population was higher than that in previous reports for central
      and northern Thailand, while the prevalence of HBV infection was similar to that
      in other regions of the country. This study clearly demonstrated a very high
      prevalence of HCV infection in northeastern Thailand, especially in the male
      population.

PMID- 9242323
TI  - Epidemiologic surveillance of visceral leishmaniasis in Sicily, Italy.
AB  - Visceral leishmaniasis (VL) is endemic in Sicily. Although it is a notifiable
      disease, there is evidence that the actual number of cases is higher than that
      reported. In 1987, a regional reference center for active surveillance of VL was
      established and it recorded a total of 284 cases through 1995, a mean of 31.5
      cases/year and about four-fold more than previously reported. Of the 284 cases,
      150 (53%) were children (< or = 14 years of age), and of the 134 adults, 39 (29%)
      were coinfected with human immunodeficiency virus (HIV). The commonest
      viscerotropic zymodeme of Leishmania infantum, MON 1, was identified in 40 (93%)
      of 43 HIV-negative and eight (57%) of 14 HIV-positive patients. Among 280
      patients evaluated (i.e., all HIV-negative and 35 of 39 HIV-positive subjects),
      254 (91%) were treated with meglumine antimoniate alone or in combination with
      other drugs; 23 (8%) received allopurinol or amphotericin B, either conventional
      or in liposomal form; and three terminally ill patients were not treated. Among
      the 245 HIV-negative patients, 236 (96%) were successfully cured, while nine (4%)
      (seven adults) died during the course of antimonial treatment. None of the 35 HIV
      positive patients was definitively cured, although mortality was apparently
      associated with other opportunistic infections.

PMID- 9242324
TI  - Risk factors for onset of cutaneous and mucocutaneous leishmaniasis in Bolivia.
AB  - A survival analysis was performed on data from an endemic area of Bolivia where
      two populations, natives and highland migrants, were living, to investigate risk
      factors for onset of cutaneous leishmaniasis (CL) and its mucosal form (MCL). In
      a first data set (703 subjects with 242 CL patients), significant risk factors
      for CL were gender, native/migrant status, activity, and home-forest distance.
      The instantaneous risk of CL increased until adolescence in both populations, and
      rapidly decreased thereafter. This risk was 3-10 times higher in migrants than in
      natives until 20 years of age, and became similar thereafter. Environmental and
      behavioral factors did not seem sufficient to explain this contrast between the
      two populations, and this evolution with age may suggest differences in the
      mechanisms involved in the development of individual protection during childhood.
      In a second data set (446 CL patients with 34 mucosal forms) the native/migrant
      status was the main factor associated with the onset of mucosal form.

PMID- 9242325
TI  - Enterotoxigenic Escherichia coli diarrhea among young children in Jakarta,
      Indonesia.
AB  - The incidence of diarrhea and enterotoxigenic Escherichia coli (ETEC) infection
      was evaluated in children six months to five years of age from an urban community
      in Jakarta, Indonesia. From January through May 1994, 408 children were monitored
      in their homes for diarrheal disease. Thirty-six percent (148 of 408) of the
      study children had at least one episode of diarrhea during the study period.
      Twenty-nine (19.6%) of the 148 children with diarrhea had ETEC isolated from a
      rectal swab sample at least once during the surveillance period; five children
      had ETEC isolated from two distinct episodes of diarrhea, giving a total of 34
      episodes of ETEC positive diarrhea in the study group. Ten of 34 episodes were
      associated with heat-labile toxin, 15 of 34 with heat-stable toxin, and seven of
      34 with both toxins. The mean age of children with diarrhea (1.7 years), whether
      ETEC positive or negative, was significantly lower than those who did not have
      diarrhea (2.4 years) during the study period; 82% of the children with ETEC were
      less than two years of age. This study demonstrates a high incidence of ETEC
      diarrhea among young children in Jakarta, and suggests this site would be
      suitable for ETEC vaccine efficacy trials.

PMID- 9242326
TI  - Seroepidemiologic evidence for murine and scrub typhus in Malang, Indonesia.
AB  - Indonesian military personnel stationed in Malang, East Java were among troops
      deployed to central Cambodia as part of the United Nations' Transition Authority
      Cambodia peace-keeping operation in 1992. Predeployment blood samples obtained
      from a cohort of Indonesian soldiers indicated a high prevalence of antibodies to
      antigens of Rickettsia typhi or Orientia (formerly Rickettsia) tsutsugamushi, the
      etiologic agents for murine and scrub typhus, respectively. To evaluate the
      potential risk of these rickettsial diseases in the Malang area, a subsequent
      seroepidemiologic survey was conducted. This study involved civilian personnel
      residing within one of three Malang kelurahans (neighborhoods) representing
      urban, suburban, and rural communities. The heads-of-households from 197 homes
      completed a detailed epidemiologic survey. In addition, blood samples were
      collected from 464 individuals residing within the households surveyed.
      Examination of civilian blood samples disclosed that 34.7% and 1.3% of the study
      participants were seroreactive to R. typhi and O. tsutsugamushi, respectively.
      These results were similar to those obtained earlier from the military samples.
      In addition, assessment of 78 blood samples obtained from peridomestic rodents
      trapped from within or near the households surveyed showed that 28 were reactive
      to R. typhi antigens and four were reactive to O. tsutsugamushi antigens. These
      data indicate that military and civilian personnel living in the Malang area of
      East Java are at risk of infection with rickettsiae that are antigenically
      indistinguishable from those that cause murine and scrub typhus.

PMID- 9242327
TI  - Speed of detection of Burkholderia pseudomallei in blood cultures and its
      correlation with the clinical outcome.
AB  - Burkholderia pseudomallei is a major cause of fatalities from nonhospital
      acquired, gram-negative bacterial septicemia in northeastern part of Thailand.
      Rapid isolation of the bacterium is critical for diagnosis and treatment.
      Bacterial culture is currently the gold standard method for laboratory diagnosis
      of melioidosis. The present study describes the time to detection of B.
      pseudomallei in blood cultures using a BacT/Alert automated blood culture system,
      and the correlation between the speed of detection and the clinical outcome of
      the patients. Of 813 consecutive positive blood cultures, 75 blood cultures from
      71 patients were positive for B. pseudomallei. The mean +/- SD time to detection
      of growth of B. pseudomallei was 23.9 +/- 14.9 hr (95% confidence interval = 20.4
      27.5 hr). A total of 62.5% of the B. pseudomallei-positive cultures was detected
      within 24 hr of incubation, and 93.1% within 48 hr. Interestingly, fatalities
      occurred in 73.7% of those in which the bacterial growth was detected within the
      first 24 hr, as compared with only 40.9% in those with a time to detection of
      culture more than 24 hr (P = 0.012). The shorter time of detection of the
      bacterial growth in blood cultures may reflect a higher bacterial level in the
      patient at the time blood was taken, and may be responsible for the poor clinical
      outcome.

PMID- 9242328
TI  - Possible occurrence of a genetic bottleneck in dengue serotype 2 viruses between
      the 1980 and 1987 epidemic seasons in Bangkok, Thailand.
AB  - Cocirculation of two genetic subtypes of dengue serotype 2 viruses was first
      observed in the 1980 epidemic season in Thailand. To further delineate the
      evolutionary history and the contribution of these subtypes to subsequent
      epidemics, we determined the envelope glycoprotein gene sequence of 20 dengue
      serotype 2 viruses isolated from infected patients during 1987 and compared them
      with those derived from earlier years. Subtype IIIa strains represented the
      majority (18 of 19) of dengue type 2 viruses derived from Bangkok metropolitan
      area, whereas all three strains from a province in the northeastern region
      belonged to subtype IIIb, indicating uneven local distribution of dengue subtypes
      within the same year. Three types of sequence variation were identified in both
      subtypes: substitutions that were unique to individual strains; substitutions
      that were shared among all subtype IIIa or IIIb viruses of both the 1980 and 1987
      epidemics; and those that were shared only among all subtypes IIIa or IIlb
      viruses of the 1987 epidemic, but were absent from the corresponding subtypes of
      1980. While the first and second types of substitution were indicative of the
      most recent random mutations and previous mutations that had been fixed in virus
      populations, respectively, the third type suggested possible occurrence of a
      genetic bottleneck and subsequent expansion of one or a limited number of subtype
      IIIa strains in Bangkok between 1980 and 1987. Immunoblot analysis of
      intracellular NS1 antigen with anti-NS1 monoclonal antibodies also revealed
      antigenic heterogeneity of the NS1 protein that correlated with the subdivision
      based on envelope protein variation.

PMID- 9242329
TI  - Fingerprinting of Ehrlichia species by repetitive element polymerase chain
      reaction.
AB  - To facilitate identification of ehrlichial pathogens, we developed a new
      technique based on fingerprints resulting from repetitive element polymerase
      chain reaction (rep-PCR). This technique uses consensus tRNA primers to generate
      amplification products that reflect distance polymorphisms between adjacent tRNA
      genes. Species-specific fingerprint patterns were obtained for seven Ehrlichia
      spp., as well as the unnamed causative agent of human granulocytotropic
      ehrlichiosis. Bands ranged in size from approximately 50 to 1,000 base pairs.
      Banding patterns varied depending on dilution of template DNA, with lower
      dilutions giving more complex banding patterns. These preliminary data indicate
      that repetitive-sequence-based PCR appears to be a useful technique for
      identifying ehrlichial organisms to the species, and perhaps the strain level.
      Compared with other conventional molecular-biologic methods, rep-PCR offers the
      advantages of ease of performance and rapid availability of results.

PMID- 9242330
TI  - Leishmania (Viannia) braziliensis: biological behavior in golden hamsters of
      isolates from Argentine patients.
AB  - This study reports intraspecific variations of native isolates of Leishmania
      (Viannia) braziliensis from patients with leishmaniasis from Salta, Argentina.
      These isolates induced skin lesions in golden hamsters, initially showing rapid
      development, reaching their largest size between 28 and 35 days postinfection
      (PI). Thereafter, the infections were self-limiting and total regression was
      observed at 80-150 days PI. The majority of the native isolates were
      characterized by low infectivity in the experimental animals, and a classic
      pattern of dissemination to systemic organs was established. However, unusual
      features for L. braziliensis were displayed by two isolates; one showed evidence
      of high infectivity in hamsters characterized by a short prepatent period and
      larger, severe and persistent lesions at the inoculation site. The other isolate,
      of low infectivity, showed cutaneous metastasis and recurrent systemic
      dissemination in the same animals, suggesting dissociation between infectivity
      and pathogenicity. Metastasis has been frequently described in hamsters infected
      with L. (V) guyanensis and L. (V) panamensis, but not in infections induced by L.
      (V) braziliensis, as was observed in this study. Active and/or regressive
      histopathologic lesions were observed, depending on the stage of the infection.
      An exudative and mixed inflammatory pattern with microabscesses and necrotic
      areas was observed during early infection, while well-defined granulomas and
      collagen formation were the predominant features detected at a later time.
      Amastigotes were easily detected in the tissues, although in low numbers.
      Schaumann bodies were always detected. The characterization of the unique
      features of these native isolates, and the verification of their reproducibility
      in vitro and in vivo will be useful tools in tests related to immunoprophylaxis
      and chemotherapy.

PMID- 9242331
TI  - Getting to the source: dendritic cells as therapeutic reagents for the treatment
      of patients with cancer.

PMID- 9242332
TI  - Generation of dendritic cells in vitro from peripheral blood mononuclear cells
      with granulocyte-macrophage-colony-stimulating factor, interleukin-4, and tumor
      necrosis factor-alpha for use in cancer immunotherapy.
AB  - OBJECTIVE: The purpose of the study was to characterize the requirements in terms
      of precursors, developmental pathways, and media for the generation of large
      numbers of mature dendritic cells (DC) under conditions acceptable for use in
      adjuvant, active immunotherapy strategies for surgically treated malignancies.
      SUMMARY BACKGROUND DATA: Although limited previously by the small numbers
      accessible, DC-based immunotherapies for malignancy have become more realistic
      with the development of methods for efficiently generating larger numbers of DC
      from peripheral blood mononuclear cells (PBMC) in vitro, but these methods rely
      on clinically unacceptable culture conditions (such as inclusion of fetal bovine
      serum), necessitating the development of methods for generating functionally
      equivalent DC in serum-free conditions. METHODS: Plastic-adherent PBMC (from
      healthy donors and patients with cancer) were incubated for 7 days with
      granulocyte-macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL
      4) with and without tumor necrosis factor-alpha (TNF-alpha) in fetal bovine serum
      containing and serum-free media and were analyzed by Wright's stain for
      morphology, flow cytometry for phenotype, and mixed lymphocyte reaction for
      allostimulatory function. RESULTS: Growth in either serum-containing or serum
      free media supplemented with GM-CSF and IL-4 yielded a similarly heterogeneous
      population of cells, 6% to 10% of which had the morphology (large cells with thin
      projections), immunophenotype (including CD83+), and function of mature DC. Tumor
      necrosis factor-alpha significantly augmented the number of these mature DC,
      whereas preculture depletion of CD14+ PBMC virtually eliminated them.
      CONCLUSIONS: Generation of mature DC in the authors' serum-free clinically
      applicable conditions is similar to serum-containing conditions and requires
      CD14+ precursors, differentiation through a CD14-CD83- immature stage under the
      influence of GM-CSF and IL-4, and maturation into a CD83+ DC under the influence
      of TNF-alpha.

PMID- 9242333
TI  - Management outcomes in splenic injury: a statewide trauma center review.
AB  - OBJECTIVE: Clinical pathways now highlight both observation and operation as
      acceptable initial therapeutic options for the management of patients with
      splenic injury. The purpose of this study was to evaluate treatment trends for
      splenic injury in all North Carolina trauma centers over a 6-year period.
      METHODS: Splenic injuries in adults over a 6-year period (January 1988-December
      1993) were identified in the North Carolina Trauma Registry using ICD-9-CM codes.
      Patients were divided into four groups by method of management: 1) no spleen
      operation, 2) splenectomy, 3) definitive splenorrhaphy, and 4) splenorrhaphy
      failure followed by splenectomy. The authors examined age, mechanism of injury,
      admitting blood pressure, and severity of injury by trauma score and injury
      severity score. SUMMARY BACKGROUND DATA: Comparisons were made between adult (17
      64 years of age) and geriatric (older than 65 years of age) patients and between
      patients with blunt and penetrating injury. Resource utilization (length of stay,
      hospital charges) and outcome (mortality) were compared. RESULTS: One thousand
      two hundred fifty-five patients were identified with splenic injury. Rate of
      splenic preservation increased over time and was achieved in more than 50% of
      patients through nonoperative management (40%) and splenorrhaphy (12%).
      Splenorrhaphy was not used commonly in either blunt or penetrating injury.
      Overall mortality was 13%. Geriatric patients had a higher mortality and resource
      utilization regardless of their mechanism of injury or method of management.
      CONCLUSIONS: Nonoperative management represents the prevailing method of splenic
      preservation in both the adult and geriatric population in North Carolina trauma
      center hospitals. Satisfactory outcomes and economic advantages accompany
      nonoperative management in this adult population.

PMID- 9242334
TI  - Simultaneous bilateral breast reconstruction with the transverse rectus abdominus
      musculocutaneous free flap.
AB  - OBJECTIVE: The purpose of the study was to assess the results and morbidity
      associated with simultaneous bilateral TRAM free flap breast reconstruction and
      describe refinements in its surgical technique. SUMMARY BACKGROUND DATA:
      Bilateral prophylactic total mastectomies might be an agreeable option for those
      patients at highest risk for breast cancer if autogenous tissue breast
      reconstruction could be performed with reasonable technical ease and acceptable
      morbidity. However, some surgeons harbor reservations regarding the extensiveness
      of the surgery, the associated morbidity, and the aesthetic quality of the
      resulting outcome. METHODS: A multicenter retrospective review of clinical
      experience with 120 consecutive patients who underwent 240 simultaneous bilateral
      TRAM free flap breast reconstructions was developed. RESULTS: The average
      operating time, including the time required for the breast ablative portion of
      the procedures, was 8.6 hours. The average length of hospitalization was 7.6
      days. However, for the last 40 patients, these figures were reduced to 7.1 hours
      and 6.1 days, respectively. Nonautologous blood transfusions were needed in 33
      cases (28%), but only 1 was required in the last 40 patients. Thromboses
      developed in six of 240 flaps (2.5%): 4 were arterial and 2 were venous. Re
      exploration allowed us to restore circulation in five flaps, whereas one flap was
      unsalvageable and was replaced successfully with an alternate flap. An
      uncomplicated deep vein thromboses developed in one patient with a history of
      recurrent deep vein thromboses that had no adverse effect on her outcome. Minor
      complications developed in 18 patients (15%) (e.g., hematoma, partial wound
      necrosis, wound infection, or prolonged postoperative ileus) that did not affect
      the long-term outcome. Fourteen patients (11.6%) had abdominal wall weakness or
      hernias. Follow-up time averaged 37.2 months (range, 14-62 months). On last
      follow-up, patients' self-reported overall satisfaction with the procedure was
      56% excellent, 40% good, and 4% fair. CONCLUSIONS: Simultaneous bilateral free
      flap reconstruction is technically feasible with a high rate of success and an
      acceptable morbidity. When performed by experienced surgeons, bilateral
      prophylactic total mastectomies combined with simultaneous bilateral TRAM free
      flap reconstruction may provide an adequate surgical option with aesthetically
      acceptable results for patients at high risk for breast cancer.

PMID- 9242335
TI  - A new prognostic strategy for gastric carcinoma: mRNA expression of tumor growth
      related factors in endoscopic biopsy specimens.
AB  - OBJECTIVE: The study analyzed the prognostic value of the transcription of
      several tumor growth-related genes in gastric carcinoma biopsy specimens. SUMMARY
      BACKGROUND DATA: The nodal status is one of the most significant prognostic
      factors in gastric carcinoma. There are, however, no satisfactory parameters for
      the preoperative assessment of nodal status. METHODS: A reverse transcriptase
      polymerase chain reaction analysis was used to analyze the transcription of
      several tumor growth-related genes in endoscopic biopsy specimens from 78 gastric
      carcinomas. The factors examined were cyclin D1, cyclin E, urokinase-type
      plasminogen activator, 72-kd type IV collagenase, vascular endothelial growth
      factor, platelet-derived growth factor-A (PDGF-A), transforming growth factor
      beta, and interleukin-10. The relation between the mRNA expression and the
      clinical pathologic parameters was analyzed statistically. RESULTS: The incidence
      of PDGF-A (p = 0.010) and transforming growth factor-beta (p = 0.009) mRNA
      expression increased as the pathologic stage advanced. Nodal metastasis
      correlated with cyclin D1 (p = 0.045), cyclin E (p = 0.037), urokinase-type
      plasminogen activator (p = 0.047), and PDGF-A (p = 0.003) mRNA. Interestingly,
      the expression of PDGF-A mRNA showed a positive correlation (p = 0.004) with the
      early presence of lymph node metastases. CONCLUSIONS: Tumor growth-related factor
      mRNA in biopsy specimens may be a new prognostic tool.

PMID- 9242336
TI  - Prospective evaluation of circulating hepatocytes by alpha-fetoprotein mRNA in
      humans during liver surgery.
AB  - OBJECTIVE: The objective of this study was to analyze the specificity of
      detecting liver tumor cell dissemination by alpha-fetoprotein (AFP) mRNA in
      peripheral blood. SUMMARY BACKGROUND DATA: Alpha-fetoprotein mRNA has been used
      for the detection of circulating micrometastatic tumor foci of hepatocellular
      carcinoma (HCC); however, the interpretation of the results has been equivocal.
      METHODS: Sixty-four consecutive patients with malignant HCC (n = 20), liver
      metastases (n = 27), or nonmalignant (n = 17) liver diseases undergoing partial
      or total hepatectomy and orthotopic liver transplantation were included in this
      prospective study from January to July 1995. Peripheral blood samples were
      obtained before surgery, during surgery, and after surgery (range, 6-15 months).
      Total mRNA was extracted from nucleated cells, and cDNA synthesis and polymerase
      chain reaction amplification (nested polymerase chain reaction in one tube) were
      performed with specific AFP primers. RESULTS: Preoperative AFP mRNA was detected
      in 20 patients (17%), of which 5 of 20 had HCC. Intraoperative assessment showed
      positive AFP mRNA values in a total of 34 patients (53%) with various causes, of
      which 8 of 20 (40%) had HCC, 17 of 27 (63%) had other malignancies, and 9 of 17
      (53%) had nonmalignant diseases. Recurrent tumor in patients with HCC occurred in
      four cases after surgery (range, 6-15 months) and did not correlate with AFP mRNA
      positivity before surgery, during surgery, or after surgery. CONCLUSIONS: Alpha
      fetoprotein mRNA in peripheral blood is not a specific marker of circulating
      micrometastases from HCC, especially in the context of surgical treatment of HCC.

PMID- 9242337
TI  - Shunt surgery during the era of liver transplantation.
AB  - OBJECTIVE: The indications for and the results of portosystemic shunts done in
      the authors' institution since initiation of a liver transplant program 10 years
      ago were reviewed. SUMMARY BACKGROUND DATA: With the widespread availability of
      liver transplantation as definitive treatment of chronic liver disease, the role
      of shunts in the overall management of variceal bleeding needs to be redefined.
      METHODS: Seventy-one variceal bleeders with cirrhosis who received a shunt (82%
      distal splenorenal shunts) because of sclerotherapy failure or because endoscopic
      treatment was not indicated were reviewed retrospectively. In 44 patients with
      well-preserved hepatic reserve, the shunt was used as a long-term bridge to
      transplantation (shunt group 1). The remaining 27 patients with shunts were not
      transplant candidates mainly because of uncontrolled alcoholism or advanced age
      (shunt group 2). Survival of both shunt groups was compared to that of 180 adult
      patients with a history of variceal bleeding who underwent transplantation soon
      after referral. RESULTS: Because of their more advanced liver disease, the liver
      transplant group had a higher operative mortality rate (19%) than did either of
      the shunt groups (5% and 7%, respectively) (p < 0.02). Kaplan-Meier survival
      analysis showed better survival in shunt group 1 (seven patients thus far
      transplanted) than in either the liver transplant group or shunt group 2 during
      the early years and superior survival of shunt group 1 and the liver transplant
      group as compared to shunt group 2 during the later years of the analysis. Only
      two patients from shunt group 1 have died of late postoperative hepatic failure
      without benefit of liver transplantation. CONCLUSIONS: A shunt may serve as an
      excellent long-term bridge to liver transplantation in patients with well
      preserved hepatic reserve. Shunt surgery still plays an important role in
      treatment of selected patients with variceal bleeding who are not present or
      future transplant candidates.

PMID- 9242339
TI  - Pancreatic resection combined with intraoperative radiation therapy for
      pancreatic cancer.
AB  - OBJECTIVE: The objective of the study was to analyze a single center's experience
      in the treatment of pancreatic carcinoma with a combination of pancreatic
      resection and intraoperative radiation therapy (IORT). SUMMARY BACKGROUND DATA:
      Pancreatic cancer is the most lethal form of gastrointestinal malignancy.
      Historically, it carries a 20% 1-year survival and a 5-year survival of 3% to 5%.
      Since 1987, patients at Thomas Jefferson University Hospital have been offered
      IORT in an attempt to improve their survival. METHODS: The authors reviewed all
      patients treated at Thomas Jefferson University Hospital with pancreatic
      adenocarcinoma from 1987 to 1994. From this population, 14 patients were
      identified who received IORT in conjunction with curative surgery. Duration of
      hospital stay, perioperative complications, duration of postoperative ileus, and
      survival were assessed by retrospective review. RESULTS: Of the 14 patients, 6
      were male and 8 were female. Patient median age was 61. Six patients had stage I
      disease, 2 had stage II, 6 had stage III. Two patients had total pancreatectomy,
      2 had distal pancreatectomy, and the remaining had pancreaticoduodenectomy
      (Whipple resection). Median survival was 16 months with a 15.5% 5-year survival.
      Postoperative complications, duration of hospital stay, and duration of
      postoperative ileus were not adversely affected by the addition of IORT when
      compared to in-house control subjects. CONCLUSIONS: Intraoperative radiation
      therapy is a useful adjunct to surgical resection as treatment of pancreatic
      cancer. The authors' data suggested it can prolong median survival and long-term
      survival without adding significant morbidity.

PMID- 9242338
TI  - Tc-99m-HMPAO white blood cell scan for diagnosis of acute appendicitis in
      patients with equivocal clinical presentation.
AB  - OBJECTIVE: The authors' goal was to evaluate the accuracy of Technetium 99m-HMPAO
      labeled leukocyte imaging for screening patients with atypically presenting
      appendicitis and to determine how availability of this test affected practice
      patterns of surgeons at the authors' medical center. SUMMARY BACKGROUND DATA:
      Appendicitis can be difficult to diagnose and in equivocal cases usually requires
      inpatient observation. The delay may increase morbidity and costs. A test that
      rules out acute appendicitis could be cost effective if it allowed early
      discharge from the emergency department. Previously, there have been no simple,
      rapid, accurate noninvasive methods for improving diagnostic accuracy in patients
      with equivocal presentations of appendicitis. METHODS: Patients referred to rule
      out appendicitis were analyzed. Patients were imaged up to 3 hours after
      injection of 10-mCi 99mTc-HMPAO-labeled autologous leukocytes (Tc-WBC), and when
      the scans became positive, imaging was terminated and the requesting physician
      notified of the results. Diagnostic accuracy was established by surgical and
      histopathologic findings or by absence of symptoms after 1 month clinical follow
      up. The source of referral, hospital length of stay, disposition of patients, and
      ancillary tests (ultrasound, computed tomographic scan, and barium enema) were
      analyzed. RESULTS: One hundred twenty-four patients were studied from November
      1991 through December 1995. Fifty-eight percent of positive scans showed uptake
      within 1 hour of injection and 73% by 2 hours. The Tc-WBC scan correctly
      identified an inflammatory source of abdominal pain in 65 of 66 cases
      (sensitivity = 98%) and was correctly negative in 55 of 58 cases (specificity =
      95%). The scan correctly diagnosed appendicitis in 50 of 51 cases (sensitivity =
      98%) and correctly excluded appendicitis in 62 of 73 cases (specificity = 85%).
      Outpatient referrals increased from 38% to 87%. In those patients with
      negativescans, inpatient observation, number of adjunctive tests, and length of
      stay decreased significantly. CONCLUSIONS: The high sensitivity and negative
      predictive value of Tc-WBC imaging may permit patients to be screened and
      discharged from the emergency department. Focally positive scans often indicate
      disease requiring operation but not in all cases. The Tc-WBC imaging reduced the
      negative laparotomy rate to 3.9% while reducing admission rates and hospital
      length of stay.

PMID- 9242340
TI  - Serum amylase level on admission in the diagnosis of blunt injury to the
      pancreas: its significance and limitations.
AB  - OBJECTIVE: The objective of this study was to elucidate the significance and
      limitations of serum amylase levels in the diagnosis of blunt injury to the
      pancreas. SUMMARY BACKGROUND DATA: Several recently published reports of analyses
      of patients with blunt abdominal trauma have indicated that determination of the
      serum amylase level on admission seemed to be of little value in the diagnosis of
      acute injury to the pancreas. Few previous reports have described clearly the
      significance and the limitations of the serum amylase level in diagnosing injury
      to the pancreas. METHODS: Retrospective analysis of 73 patients with blunt injury
      to the pancreas during 16-year period from February 1980 to January 1996 was
      performed. The factors analyzed in the current study included age, gender, time
      elapsed from injury to admission, hypotension on admission, type of injury to the
      pancreas, intra-abdominal- and intracranial-associated injuries, and death.
      RESULTS: The serum amylase level was found to be abnormal in all patients
      admitted more than 3 hours after trauma. Various comparisons between patients
      with elevated (n = 61, 83.6%) and nonelevated (n = 12, 16.4%) serum amylase
      levels showed the statistical significance solely of the time elapsed from injury
      to admission (7 +/- 1.5 hours vs. 1.3 +/- 0.2 hour, p < 0.001). The major factor
      that influences the serum amylase level on admission appeared to be the time
      elapsed from injury to admission. Determination of the serum amylase level is not
      diagnostic within 3 hours or fewer after trauma, irrespective of the type of
      injury. CONCLUSIONS: To avoid failure in the detection of pancreatic injury, the
      authors advocate determination of serum amylase levels more than 3 hours after
      trauma.

PMID- 9242341
TI  - Unopposed interleukin-1 is necessary for increased plasma cytokine and eicosanoid
      levels to develop in severe sepsis.
AB  - OBJECTIVE: The purpose of the study was to identify the changes in plasma
      prostaglandin, leukotriene, and cytokine levels during clinical severe sepsis for
      which interleukin-1 was necessary. SUMMARY BACKGROUND DATA: Circulating
      prostaglandins, leukotrienes, and cytokines have been implicated as causative
      agents of systemic inflammation due to sepsis. However, interactions between
      interleukin-1 and the other cytokine and eicosanoid mediators of severe sepsis
      are not well-defined. METHODS: As part of two sequential multisite, prospective,
      randomized, double-blind, placebo-controlled clinical trials, 37 patients with
      severe sepsis received interleukin-1 receptor antagonist (IL-1ra) 100-mg bolus
      followed by 2 mg/kg per hour intravenously for 72 hours (n = 20) or placebo (n =
      17). Plasma thromboxane B2 (TxB2), prostaglandin 6-keto-F1alpha (PGI),
      leukotriene B4 (LTB4), leukotriene C4D4E4 (LTC4D4E4), interleukin-1 beta (IL-1),
      interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were measured
      by enzyme-linked immunosorbent assay before study drug infusion (baseline) and at
      24, 48, and 72 hours after the beginning of the study drug infusion. RESULTS:
      Differences between placebo and IL-1ra for plasma LTB4 were not significant, but
      only IL-1ra LTB4 increased from baseline. Plasma TxB2, PGI, LTC4D4E4, TNF, and IL
      6, expressed as % baseline, decreased significantly in patients receiving IL-1ra
      compared with the placebo group (p < 0.05), whereas plasma IL-1 increased
      significantly. CONCLUSIONS: Interleukin-1 may be a necessary mediator of
      increased circulating PGI, TxB2, LTC4D4E4, TNF, and IL-6 levels in patients with
      severe sepsis. Plasma IL-1 and LTB4 are increased with infusion of IL-1 receptor
      antagonist. The clinical significance of IL-1 in modifying circulating eicosanoid
      and cytokine concentrations in clinical sepsis is not clear from the data.

PMID- 9242342
TI  - Preservation of recurrent laryngeal nerve invaded by differentiated thyroid
      cancer.
AB  - OBJECTIVE: This study was undertaken to determine whether the recurrent laryngeal
      nerve involved in differentiated thyroid carcinoma could be preserved. SUMMARY
      BACKGROUND DATA: Few investigations have provided definitive results concerning
      preservation of the recurrent laryngeal nerve involved in thyroid cancer.
      Complete excision with resection of the recurrent laryngeal nerve reportedly did
      not improve survival over incomplete excision in differentiated thyroid
      carcinoma. METHODS: A retrospective study was performed with the medical records
      of 50 patients with differentiated carcinoma and preoperative normal vocal cord
      function to investigate outcomes of recurrent laryngeal nerve preservation
      including local recurrence, prognosis, and postoperative vocal cord function. The
      recurrent laryngeal nerves on 1 or both sides were preserved in 23 patients (the
      preserved group), whereas the involved recurrent laryngeal nerve of the other 27
      patients was resected (the resected group). RESULTS: Backgrounds of patients were
      similar between the resected and preserved groups. The number of patients with
      recurrences in each group was similar, and incidence of local, regional, and
      distant metastatic recurrences were not different between the groups.
      Postoperative overall survival of the preserved group was similar to that of the
      resected group (p = 0.1208). More than 60% of patients or of nerve at risk in the
      preserved group restored normal vocal cord function within 6 months. Some
      functional vocal cord movement was recognized in 80% of patients or of nerve at
      risk. All patients in the resected group including patients with nerve
      anastomosis showed permanent paralysis of the ipsilateral vocal cord.
      CONCLUSIONS: These results suggested that the recurrent laryngeal nerve, even if
      infiltrated by differentiated thyroid cancer, is worthwhile to preserve for
      maintenance of postoperative vocal cord function without affecting the incidence
      of local recurrence or prognosis.

PMID- 9242344
TI  - Prognostic factors in hilar cholangiocarcinoma.

PMID- 9242343
TI  - Anorectal surgery in patients infected with human immunodeficiency virus: factors
      associated with delayed wound healing.
AB  - OBJECTIVE: A review of all anorectal operations in patients infected with human
      immunodeficiency virus (HIV) was performed to assess the incidence, variety, and
      clinical course of anorectal disease in these patients and to identify factors
      influencing wound healing. SUMMARY BACKGROUND DATA: Anorectal disease is the most
      common indication for surgical intervention in patients infected with HIV. The
      cause and management of HIV-related anorectal conditions, which differ
      significantly from non-HIV-related diseases, are not clear. There also is
      considerable variation in the reported results of surgical procedures, including
      wound healing. St. Vincent's Hospital, Sydney, is situated in an area with the
      highest concentration of individuals infected with HIV in Australia. METHODS: The
      medical records of all identified patients infected with HIV who had an anorectal
      operation at St. Vincent's General Hospital between January 1, 1988, and January
      31, 1995, were reviewed retrospectively. Logistic regression, Mann-Whitney U
      test, and Fisher's exact tests were used for analysis. RESULTS: One thousand five
      hundred two patients with acquired immune deficiency syndrome (AIDS), equivalent
      to 26.8% of all known patients with AIDS in Australia at this time, were admitted
      to this hospital during the 7-year period. One hundred one patients infected with
      HIV underwent 161 anorectal operations. All patients were male homosexuals (98
      patients, 97%) or bisexuals (3 patients, 3%), with intravenous drug use an
      additional risk factor in 5 patients (5%). Thirty-seven percent of patients had
      more than one operation. Seventy-two percent of patients were Centers for Disease
      Control (CDC) group 4 (AIDS) at operation, 27% were group 2, 1% was group 3, and
      none were group 1. Accurate information about wound healing was available for 74%
      of first operations, and univariate and multivariate logistic analyses of these
      showed that when the CD4+ T-lymphocyte count was <50 cells/ microL, healing was
      significantly retarded (p = 0.016). The Centers for Disease Control group,
      patient age, and serum albumin were not significant predictors of wound healing.
      The interval between HIV diagnosis and operation was not associated with impaired
      wound healing, but recognition of AIDS more than 1 year before operation was
      associated with significantly better wound healing compared with those in whom
      AIDS developed within the year before operation (p = 0.025). In the patients for
      whom accurate wound healing information was available, only 40% had healed their
      wounds by 3 months after operation. Wound healing was worst for patients with
      chronic fissures, only 16% of whom had healed their wounds at 3 months. The wound
      healing rate was worse for repeat operations than for first operations. Ten
      percent of patients had anorectal malignancies, none of which were diagnosed
      clinically before or during operation. CONCLUSIONS: Wound healing is a
      significant problem after anorectal operations in patients infected with HIV,
      especially when the CD4 count is <50/microL. Although there seems to be little or
      no benefit from more invasive operations in some cases, thorough examination with
      adequate biopsies is required in all cases. The best management of anorectal
      disease in patients infected with HIV still is unclear.

PMID- 9242345
TI  - Excess pyruvate and lactate production occurs in sepsis and is not caused by
      anaerobic glycolysis.

PMID- 9242346
TI  - Tension-free fundoplication can be performed without greater curvature
      mobilization.

PMID- 9242347
TI  - Effect of ibuprofen pretreatment on the production of cytokine and hormone after
      open cholecystectomy.

PMID- 9242348
TI  - Laparoscopic splenectomy.

PMID- 9242349
TI  - The utility of a rigid protocol for scanning patients with gastrointestinal
      hemorrhage.

PMID- 9242350
TI  - Simultaneous repair of bilateral inguinal hernias under local anesthesia.

PMID- 9242351
TI  - Protective effect of flavonoids on doxorubicin-induced cardiotoxicity.
AB  - We have examined the effect of alpha G-Rutin and luteolin on doxorubicin (DOX)
      toxicity in mice. In the heart, the lipid peroxide level, increased to 1.5 times
      of the normal level induced by DOX, decreased to the normal level after treatment
      with alpha G-Rutin or luteolin (i.p.). Glutathione peroxidase (GSHpx) activity,
      decreased to 73% of normal activity after DOX treatment, was shown to recover by
      the combined flavonoids. The lipid peroxide level in bone marrow cells increased
      to 5.9 times of the normal level by DOX treatment, whereas this level in the
      extra bone marrow cells did not change by treatment with DOX. The combination of
      alpha G-Rutin and luteolin with DOX significantly inhibited the DOX induced
      increment of the lipid peroxide level in bone marrow cells. Flavonoids have also
      reduced the effect of DOX toxicity by oral administration. It is suggested that
      it is possible to reduce DOX toxicity by the intake of food including flavonoids.
      In NADPH-dependent lipid peroxidation, alpha G-Rutin and luteolin showed
      concentration-dependent inhibition. Therefore, we considered that the reduction
      effect of DOX toxicity by flavonoids was caused by antioxidative action and other
      effect of the flavonoids.

PMID- 9242352
TI  - Brain capillary lesions produced by cocaine in rats.
AB  - In the last 20 years, acute and chronic cocaine addiction has increased among
      young and adult people. The effects of cocaine on brain vasculature of young
      animals have not been histologically studied in depth. In the present study, we
      report the lesions of brain capillaries, including the choroid plexus, produced
      by chronic cocaine administration, in adult Wistar rats receiving i.p., 30
      mg/kg/day of aqueous cocaine hydrochloride solution. Rats were sacrificed after
      several days of treatment. Histopathological examination of capillaries from
      different brain regions and cerebellum was performed using light microscopy. At 7
      days, there were initial signs of dilatation, rupture and thrombosis of
      capillaries. At 15 days of treatment small interstitial oedema and hemorrhages by
      rupture of the basal membrane of the capillaries was found. At 30 days of
      treatment, many capillaries from different areas showed fibroid endothelial
      thickening, and wall fibrosis become evident after 60 days of daily cocaine. In
      numerous places (cortex, gray nucleus: thalamus, caudate, hippocampus and
      cerebellum) we observed capillaries with an occluded lumen probably due to
      fibrosis or thrombi after 90 days of treatment. In the latter treatment,
      capillaries from the choroid plexuses had their lumen dilated and the epithelial
      cells vacuolated or necrotic. We hypothesize that the chronic administration of
      cocaine in rats induced brain lesions in part as a result of capillary disruption
      and subsequent extravasation of erythrocytes to brain parenchyma.

PMID- 9242353
TI  - Haematological and erythrocyte membrane changes induced by methacrylonitrile.
AB  - The effect of methacrylonitrile (MeAN) a cyanogen compound, on various
      haematological parameters was studied. Administration of MeAN at 100 mg/kg per
      body weight/day for 7 days resulted in a significant decrease in the red cell
      count and in the level of hemoglobin, probably by inducing hemolysis. MeAN
      altered the fluidity of the erythrocyte membrane by increasing membrane
      cholesterol while the phospholipid remained unchanged, followed by a decrease in
      the activities of membrane bound enzymes like (Na+, K +)-ATPase, Acetylcholine
      esterase and NADH-dehydrogenase. A significant decrease in membrane sialic acid
      and calcium were also observed in the treated animals. MeAN besides having
      various toxic side effects, also exerts its toxicity on the circulating
      erythrocytes.

PMID- 9242354
TI  - Dietary restriction modulated carcinogen-DNA adduct formation and the carcinogen
      induced DNA strand breaks.
AB  - Dietary restriction (DR) alters the activities of hepatic drug metabolizing
      enzymes and modulates the formation of carcinogen-DNA adducts in carcinogen
      treated animals. Our previous results showed that a 40% restriction of diet (60%
      of ad libitum (AL) food consumption) reduced the hepatic metabolic activation of
      aflatoxin B1 (AFB1) but increased the activation of benzo[a]-pyrene (BaP) in both
      rats and mice. In this study, the focus was directed toward the levels of
      carcinogen-DNA adducts formation and the carcinogen-induced DNA strand breaks in
      mouse kidney and liver DNA. DR significantly inhibited both AFB1-DNA adduct
      formation and AFB1-induced DNA strand breaks in kidney DNA of mice that received
      a single dose of [3H]AFB1 (5 mg/kg). The levels of AFB1-DNA adduct formation in
      mouse kidney DNA correlated well with increased AFB1-induced DNA strand breaks.
      The correlation between the levels of AFB1-DNA-adducts formed and DNA strand
      breaks in kidney DNA of DR-mice was less linear than between its AL-counterpart
      suggesting that other factors, such as different rates of DNA repair, may be
      involved. In addition, DR enhanced hepatic BaP- and 6-nitrochrysene (6-NC)-DNA
      adduct formation in the mice treated with BaP and 6-NC, respectively. The
      formation of the specific BaP-adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy
      7,8,9,10-tetrahydro-BaP (N2-dG-BaP), in mouse liver was proportional to the dose,
      and was compatible to the BaP-induced DNA strand breaks affected by DR. The
      enhancement of the total 6-NC-DNA adduct formation in DR-mouse was also in
      correlation with the increased 6-NC-induced DNA strand breaks. The activity of
      mouse liver microsomal nitro-reductase increased by 2-fold in response to DR
      indicating that the nitroreduction may contribute to the increase of the
      metabolic activation of 6-NC. Our present results indicate that the effect of DR
      on the carcinogen activation is dependent upon the DR-modulated carcinogen
      metabolizing enzyme activities.

PMID- 9242355
TI  - Acute hematopoietic toxicity of aniline in rats.
AB  - In the present study, acute hematopoietic toxicity of aniline as a function of
      time was investigated in rats. The animals were given a single oral dose of
      aniline hydrochloride (2 mmol/kg) and euthanized at zero (control), 0.25, 0.5, 1,
      3, 6, 12, 24 and 48 h following the treatment. The blood methemoglobin level
      increased dramatically and attained a peak level of 37% (31 fold greater than the
      controls) at 0.5 h. Thereafter, the increases were less pronounced and the level
      declined with time. Spleen weight to body weight ratio remained unchanged up to
      24 h, but increased approximately 25% at 48 h. Lipid peroxidation (MDA content)
      in the spleen increased by 39% at 24 h and remained steady even at 48 h. MDA
      protein adducts, as quantitated by a competitive ELISA, showed 94, 126 and 265%
      increases in the spleen homogenates at 12, 24 and 48 h, respectively, following
      the treatment. However, no changes were observed in the splenic protein
      oxidation. Morphological examination showed congestion of splenic blood vessels
      and marked expansion of red pulp at 24 and 48 h. These studies suggest that
      aniline related changes in the blood are reflected very early as evident from
      increases in the methemoglobin content, whereas changes in the spleen appear
      later and are characterized by splenic weight changes, increased lipid
      peroxidation, MDA-protein adduct formation and morphological changes after a
      single high dose exposure. The increased lipid peroxidation in the spleen also
      suggests that free radical-mediated reactions could be the potential mechanism of
      splenic toxicity of aniline and lipid peroxidation precedes protein oxidation.

PMID- 9242356
TI  - In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other
      monoterpenoid compounds.
AB  - beta-myrcene (MYR) is an acyclic monoterpene found in the essential oils of
      several useful plants such as lemongrass (Cymbopogon citratus), hop, bay, verbena
      and others. Recently it has been reported that MYR as well as lemongrass oil
      blocked the metabolic activation of some promutagens (e.g., cyclophosphamide and
      aflatoxin B1) in in vitro genotoxicity assays. The present study was performed to
      evaluate the inhibitory effects of MYR and some other monoterpenoid compounds on
      microsomal enzymes involved in the activation of genotoxic substances. The
      effects of MYR and other monoterpenes on the activity of pentoxyresorufin-O
      depenthylase (PROD), a selective marker for CYP2B1, was determined in a pool of
      liver microsomes prepared from phenobarbital-treated rats. The effect of MYR on
      the activity of ethoxyresorufin-O-deethylase (EROD), a marker for CYP4501A1, was
      investigated in liver microsomes of untreated rats. Results revealed that MYR had
      almost no effect on EROD (IC50 > 50 microM), but produced a concentration
      dependent inhibition of PROD activity (IC50 =0.14 microM). The analysis of
      alterations produced by MYR on PROD kinetic parameters (Lineweaver-Burk plot)
      suggested that inhibition is competitive (Ki = 0.14 microM). The inhibitory
      effects of seven other monoterpenes on PROD activity (pentoxyresorufin 5 microM)
      were also studied and the IC50 were as follows: (-)-alpha-pinene, 0.087 microM;
      (+)-alpha-pinene, 0.089 microM; d-limonene, 0.19 microM; alpha-terpinene, 0.76
      microM; citral, 1.19 microM; citronellal, 1.56 microM, and (+/-) camphor, 7.89
      microM. The potent inhibitory effects on CYP4502B1 suggest that MYR, and other
      monoterpenes, interfere with the metabolism of xenobiotics which are substrates
      for this isoenzyme.

PMID- 9242357
TI  - Brain and plasma levels of cocaine and benzoylecgonine in lead-expose and cadmium
      exposed rats following acute or chronic intraperitoneal administration of
      cocaine.
AB  - Previous investigations of metal/cocaine interactions have shown that chronic
      oral exposure to inorganic lead or cadmium attenuates the psychoactive effects of
      acute or repeated administration of cocaine. The purpose of this investigation
      was to assess the possibility that such interactive effects may derive from metal
      induced disturbances in cocaine pharmacokinetics, i.e., delivery of cocaine to
      critical biologic sites may be disrupted by metal contamination. In this study,
      adult male rats were exposed to purified diets containing 250 ppm lead acetate
      (Group Lead), 100 ppm cadmium chloride (Group Cadmium), or unadulterated
      laboratory chow (Group Control); n = 48/exposure condition. Following ad libitum
      access to their respective diets in the home cage for 45 days, half the animals
      from each exposure regimen received single daily IP injections of 5, 10, or 20
      mg/kg cocaine HCl for a period of 7 days (n = 8/group). The remaining half the
      animals received repeated daily injections of saline during this pretreatment
      phase. On the day following pretreatment, animals previously receiving cocaine
      injections were administered a single cocaine test challenge at a dose equal to
      that received in pretreatment. Similarly, saline pretreatment animals received
      either 5, 10, or 20 mg/kg cocaine. The results of this investigation did not
      reveal reliable evidence of metal-related differences in brain levels of cocaine.
      Plasma cocaine and benzoylecgonine (BE) levels also were essentially the same for
      control and metal-exposed animals. The failure to show that lead or cadmium
      alters the disposition of cocaine in brain or plasma underscores the need to
      pursue alternative accounts of metal/cocaine interactions.

PMID- 9242358
TI  - Effects of chronic lead exposure on [3H]MK-801 binding in the brain of rat.
AB  - We have used quantitative autoradiographic methods to determine the effects of
      chronic lead exposure on N-methyl-D-aspartate (NMDA) receptors in the brain of
      female rat. Rats were exposed pre- and post-natally from day 4 +/- 1 post
      conception with 1000 ppm lead in their drinking water. This treatment continued
      after weaning. No effects of lead on [3H]MK-801 binding were found at PN 28.
      However, lead caused a significant increase in [3H]MK-801 binding in the
      hippocampus including CA1 and CA2, and in the occipital and temporal cortical
      areas at PN 56 and at PN 112. An increase in binding was also found in the
      entorhinal cortex and the dentate gyrus at PN 112. Because the NMDA receptor is
      involved in learning and memory, the lead-induced disruption of NMDA receptors in
      the hippocampus and cortex may be associated with the cation-induced cognition
      deficits.

PMID- 9242359
TI  - alpha-Tocopheryl hemisuccinate administration increases rat liver subcellular
      alpha-tocopherol levels and protects against carbon tetrachloride-induced
      hepatotoxicity.
AB  - Rats were administered a series of tocopherol analogs 18 h prior to a hepatotoxic
      dose of carbon tetrachloride (CCl4). Of the compounds tested, only d-alpha
      tocopheryl hemisuccinate (TS) provided significant protection against CCl4
      induced hepatotoxicity. No protection was observed with either d-alpha-tocopherol
      (alpha-T) or a tocopherol succinate ether derivative, d-alpha
      tocopheryloxybutyric acid (TSE). None of the tocopherol analogs significantly
      inhibited CYP2E1 activity as measured by oxidation of p-nitrophenol. Liver
      homogenates and subcellular fractions (cytosol, nuclei, plasma membranes,
      mitochondria and microsomes) were collected 18 h after tocopherol analog
      administration in the absence of CCl4. Homogenate and subcellular alpha-T levels
      were not significantly increased following TSE administration but were increased
      2-3 fold following TS and alpha-T administration. Total tocopherol levels (alpha
      T+ TS + TSE) in liver homogenates and subcellular fractions were highest in rats
      supplemented with TS. In these animals, TS was detected in all subcellular
      fractions and total tocopherol levels were increased from 6-23 fold over those
      seen in controls and 2-9 fold over alpha-T treated rats. In vitro studies in
      which liver homogenates and subcellular fractions were peroxidized with ascorbate
      and ADP/Fe suggest that increasing levels of alpha-T but not TS correlates with
      increased protection against lipid peroxidation. These results suggest that the
      ability of TS to protect against CCl4-induced hepatotoxicity relates to its
      enhanced hepatic accumulation and subsequent hydrolysis to alpha-T.

PMID- 9242360
TI  - Amyloid beta-protein precursor: a new anticoagulant?

PMID- 9242361
TI  - Electrolyte transport in biliary epithelia.

PMID- 9242362
TI  - Vancomycin-resistant enterococci: clinical, microbiologic, and epidemiologic
      features.
AB  - Enterococci have emerged as important nosocomial pathogens with increasing
      antimicrobial resistance. Within the past 5 years, vancomycin-resistant strains
      have disseminated throughout the United States and Europe. Many of these
      organisms are also highly resistant to beta-lactams and aminoglycosides, making
      them virtually untreatable. Because optimal therapy for these infections is
      unknown, attributable mortality rates for patients with vancomycin-resistant
      enterococcal bacteremia are extremely high. Recently identified risk factors for
      acquisition include prolonged hospitalization, prior antibiotic use, and serious
      underlying illness. Until effective therapy is available, prevention of infection
      by proper infection control procedures and judicious antibiotic use is critical.

PMID- 9242363
TI  - Stimulus responses and amyloid precursor protein processing in DAMI
      megakaryocytes.
AB  - Platelets, when released as anuclear cells by their precursor megakaryocytes,
      already carry soluble proteolytic fragments of the amyloid precursor protein
      (APP) within their alpha-granules and intact APP in the alpha-granule membranes.
      In response to activation signals elicited by physiologic stimuli such as
      thrombin, platelets release their granules' soluble contents and translocate
      granule membrane-bound proteins to the plasma membrane. Because platelets carry
      >90% of the circulation's APP, activated platelets have been implicated as
      origins of the beta-amyloid peptide fragment of APP (A beta), whose deposition in
      the cerebrovasculature is characteristic of Alzheimer's disease. We have
      therefore studied the APP contents and proteolytic processing in resting DAMI
      human megakaryocytic cells, along with the consequences of the activation of
      these cells by thrombin, comparing the results in each case to those with human
      platelets. Resting and PMA-differentiated DAMI cell contents were examined by
      Western blotting, immunoprecipitation, or metabolic labeling with sulfur 35
      labeled methionine during culture, while plasma membrane-bound APP was evaluated
      by flow cytometry. Activation was followed by changes in cytoplasmic calcium
      concentration ((Ca++)in) and in membrane potential. Like platelets, DAMI cells
      exhibited a thrombin dose-dependent delta(Ca++)in, and membrane potential change;
      in contrast to the surface of a platelet, the surface of an agranular resting
      DAMI cell expresses granule-membrane proteins (APP and CD63) that appear on
      platelets only after activation. DAMI cell culture with 35S-labeled methionine
      confirmed that megakaryocytes synthesize large amounts of APP, of slightly higher
      molecular weight, and degrade their APP extensively before platelets are formed.

PMID- 9242364
TI  - The role of calcium in human lymphocyte DNA repair ability.
AB  - DNA repair ability is reduced in a variety of pathologic conditions. In addition,
      in some of these diseases a disturbance in cellular Ca homeostasis occurs or
      cytosolic (Ca2+) responses to various stimuli are impaired. The leading
      environmental cause for genomal DNA damage is ultraviolet (UV) irradiation. The
      aims of the present study were (1) to evaluate a possible dependence of UV
      induced DNA repair ability on cytosolic Ca2+ in human lymphocytes and (2) to
      assess the direct effect of UV irradiation on Ca2+ homeostasis in these cells. UV
      induced DNA repair ability in lymphocytes was maximal at 1 mmol/L CaCl2 in the
      medium. Suppression of DNA repair ability occurred after elevation or reduction
      of cellular (Ca2+) when various methods were used, including changes in Ca2+
      concentration in the medium, cellular Ca2+ depletion by ethyleneglycol-bis-(beta
      aminoethylether)-N,N,N',N'-tetraacetic acid, excessive Ca2+ concentration induced
      by ionophore, and shortening of Ca2+ presence time during repair synthesis. UV
      irradiation caused an immediate and significant rise in cytosolic (Ca2+) that was
      the result of both enhanced Ca2+ uptake and inhibition of plasma membrane Ca
      adenosine triphosphatase activity. The tyrosine kinase inhibitor genistein
      inhibited both UV-induced DNA repair and UV-induced cytosolic (Ca2+) elevation.
      These results emphasize the importance of a precise cellular Ca2+ level
      regulation for the optimal DNA repair process. UV irradiation, by inducing
      cellular Ca2+ rise, may activate DNA repair as soon as DNA is damaged.

PMID- 9242365
TI  - Actinomycin D treatment leads to differentiation and inhibits proliferation in
      rhabdomyosarcoma cells.
AB  - Human embryonal cell line RD is derived from rhabdomyosarcoma, a tumor of
      childhood that arises from rhabdomyoblasts probably arrested somewhere along
      their pathway to maturation. Because actinomycin D is a drug of choice in the
      treatment of rhabdomyosarcomas, and because it has been used to induce
      differentiation as an alternative therapy for myeloproliferative syndromes, we
      treated RD cells with different concentrations of actinomycin D and evaluated the
      effects on growth and differentiation. Actinomycin D treatment in vitro caused
      time- and dose-dependent growth inhibition. Interestingly, RD cells treated with
      low doses (2.85 and 5.7 nmol/L) of actinomycin D for 6 days showed morphologic
      and phenotypic differentiation, with increased expression of desmin, alpha
      actinin, and tropomyosin. However, treatment with 11.4 nmol/L actinomycin D
      strongly inhibited growth and had cytotoxic effects that prevented the cells from
      attaining myogenic differentiation. We conclude that exposure of this human
      embryonal rhabdomyosarcoma cell line to low concentrations of actinomycin D
      released the neoplastic cells from their blockade, allowing them to recover
      normal myogenic development. We suggest a potential role for differentiation
      therapy in the treatment of rhabdomyosarcomas.

PMID- 9242366
TI  - Pregnancy increases mobilization of lead from maternal skeleton.
AB  - The question of the extent of lead mobilization from the maternal skeleton during
      pregnancy and lactation is one of the most outstanding problems of lead toxicity.
      We have undertaken a longitudinal cohort study in an urban environment of
      European female immigrants of child-bearing age (18 to 35 years) to Australia
      whose skeletal lead isotopic composition has been determined to be different from
      that in their current environment. The cohort was to consist of 100 immigrants
      anticipated to provide 20 pregnant subjects who would be compared with two groups
      of control subjects: a matched immigrant nonpregnant control group and second
      generation Australian pregnant control subjects. Pregnant subjects also serve as
      their own controls for a comparison of changes during gestation with those before
      conception. High-precision lead isotopic compositions and lead concentrations are
      measured in maternal blood and urine prenatally, monthly during gestation, and
      postnatally for 6 months; they are also measured in infant blood and urine for 6
      months; environmental measures are sampled quarterly for 6-day duplicate diet,
      house dust and water, and urban air and gasoline. Because of continuing public
      health concerns about lead exposure, interim findings from this cohort are being
      reported. To date there have been 13 conceptions in immigrant subjects, with 7
      births, in addition to 3 conceptions in the Australian control group, with 2
      births. PbBs have been generally low, with a geometric mean of 3.0 microg/dl, and
      have ranged from 1.9 to 20 microg/dl. Increases in PbB of approximately 20%
      during pregnancy have been detectable even in subjects with low blood lead
      levels. The skeletal contribution to blood lead level, based on isotopic
      measurements, has exhibited a mean increase (and standard deviation) of 31% +/-
      19% with a range from 9% to 65%. Earlier studies that used lead concentrations
      only have suggested that blood lead levels increased only during the second half
      of pregnancy. This increase in blood lead levels has also been observed in the
      present study. However, in two subjects the increases in total blood lead were
      also detected in the first 2 months of pregnancy. Changes in isotopic composition
      and blood lead during gestation for Australian pregnant controls were negligible.
      The ratio of cord/maternal blood lead levels varied from 0.54 to 1.05, and the
      ratio for the isotopic composition was 0.993 to 1.002. Results of this study
      confirm that lead is mobilized from skeletal stores at an accelerated rate during
      pregnancy and is transferred to the fetus. These results also show that
      mobilization from long-term stores (i.e., bone) contributes significantly to
      blood lead levels during pregnancy. Furthermore, exposure of the fetus to lead
      during pregnancy has implications for interpretations of neurobehavioral
      disorders attributed to only postnatal exposure. Even after 800 days of residence
      in Australia, the contribution of European skeletal lead to blood lead in
      nonpregnant subjects can be on the order of 50%, but the current PbB may give no
      indication of the former high skeletal lead burden.

PMID- 9242367
TI  - Clinical assessment of the significance of platelet-derived growth factor in
      patients with immunoglobulin A nephropathy.
AB  - To examine the role of platelet-derived growth factor (PDGF) in the pathogenesis
      of IgA nephropathy (IgAN), we investigated the expression of PDGF and the PDGF
      receptor in glomeruli with immunohistochemistry, the plasma levels of PDGF with
      ELISA, and the expression of PDGF in peripheral blood monocytes (PBMCs) with
      reverse transcription polymerase chain reaction (RT-PCR). We also assessed the
      effect of corticosteroid therapy on the plasma levels of the PDGF B-chain. At the
      time of kidney biopsy, the expression of the PDGF B-chain and the PDGF beta
      receptor in the glomeruli was upregulated in patients with IgAN. In addition, the
      plasma concentration of the PDGF B-chain was significantly higher in patients
      with IgAN than in normal subjects. Moreover, mRNA expression of PDGF beta-chain
      in PBMCs was up-regulated in patients with IgAN when compared with other patients
      with glomerulonephritis. We divided the patients into two groups according to the
      grade of urinary protein excretion (U[p]) after corticosteroid therapy. In
      patients in group 1 in whom U(p) was decreased by more than 50% or 1 gm/day after
      corticosteroid therapy, the expression of the PDGF B-chain and the PDGF beta
      receptor in the glomeruli was up-regulated. Finally, corticosteroid therapy
      decreased the plasma levels of PDGF B-chain in patients in group 1. Up-regulation
      of the PDGF B-chain and beta receptor in the glomeruli, elevated plasma levels of
      PDGF B-chain, and increased expression of PDGF mRNA in PBMCs could be associated
      with the pathogenesis of IgAN. The plasma concentration of PDGF B-chain may be a
      useful marker for patients with IgAN who would be responsive to corticosteroid
      therapy.

PMID- 9242368
TI  - Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid
      glycoprotein, and C-reactive protein.
AB  - Based on previous studies we hypothesized that interleukin-6 (IL-6) plasma levels
      would increase during the menstrual cycle, in analogy to the increase in IL-1
      levels seen during the luteal phase. Thus we have investigated menstrual cycle
      associated changes in IL-6, alpha1 acid glycoprotein (AGP), and C-reactive
      protein (CRP). The study design was cross-sectional and was conducted in 18
      healthy premenopausal women with regular menstrual cycles and in 15 age-matched
      men. The women had blood drawings in the follicular phase, at midcycle, and in
      the luteal phase of the menstrual cycle. A single blood sample was obtained from
      men to compare IL-6 levels between sexes. The median IL-6 level was 0.68 pg/ml
      (95% confidence interval (CI): 0.60 to 1.05) in the follicular phase and did not
      change significantly during the menstrual cycle. IL-6 levels did not differ
      between women and men (0.79 pg/ml; CI: 0.66 to 1.05; p > 0.05). Median AGP levels
      decreased by 6% (CI: -14% to 1%) during the luteal phase (p = 0.005), and a
      significant correlation between mean AGP and IL-6 levels was found (r = 0.60; p =
      0.01). Median CRP levels increased by 44% (CI: 27% to 59%; p < 0.001) at midcycle
      and by 31% (CI: 17% to 68%; p = 0.002) in the luteal phase, and there was a
      significant correlation between the relative increase in CRP at midcycle and the
      relative increase in progesterone levels during midcycle (r = 0.60; p = 0.01) and
      the luteal phase (r = 0.71; p = 0.001). In conclusion, we found no sustained
      menstrual cycle-dependent changes in systemic IL-6 plasma levels. AGP and CRP
      levels may be differentially regulated during the menstrual cycle of healthy
      women: AGP levels correlated with IL-6 levels, and AGP levels decreased during
      the menstrual cycle, whereas CRP levels increased during the menstrual cycle and
      correlated with the increase in progesterone levels. The reason for the observed
      changes in CRP levels remains to be elucidated.

PMID- 9242369
TI  - Effect of chronic salt loading on kidney function in early and established
      diabetes mellitus in rats.
AB  - Glomerular hyperfiltration and renal hypertrophy are among the events that
      characterize the early course of diabetes mellitus in rats and human patients.
      Previous studies from this laboratory demonstrated that salt restriction
      paradoxically reduces total renal vascular resistance (RVR) and increases
      glomerular filtration rate (GFR) in diabetic rats (J Am Soc Nephrol 1995;5:1761
      7). In the present study we examined the converse condition by testing the
      effects of chronic salt loading on kidney function in moderately hyperglycemic
      insulin-treated rats with early and established streptozotocin diabetes. Salt
      loading was accomplished by adding 1% NaCl to the drinking water 1 day or 35 days
      after diabetes was induced. The high-salt diet appropriately increased salt
      excretion in diabetic rats and nondiabetic controls. GFR and renal plasma flow
      were determined by inulin and para-amino hippuric acid (PAH) clearance 7 days
      after salt loading was started. Diabetic rats receiving tap water exhibited
      hyperfiltration with no change in renal blood flow (RBF). In nondiabetic rats,
      salt loading caused a reduction in total RVR and proportional increases in RBF,
      GFR, and kidney weight (KW). Salt loading in early diabetes did not affect RVR,
      RBF, or KW and caused a paradoxical reduction in GFR. In established diabetes,
      salt loading reduced RVR and increased RBF, similar to results in nondiabetic
      rats, but as in rats with early diabetes, it did not increase GFR or KW. In
      summary, although the response in RVR and RBF to chronic salt loading depends on
      the duration of diabetes, the increase in GFR and KW as seen in nondiabetic rats
      is blunted in the early and established state of insulin-treated diabetes in
      rats. These findings further support the notion that the renal response to
      variation in salt intake is altered in insulin-treated diabetes in rats.

PMID- 9242370
TI  - Increased red cell glutamine availability in sickle cell anemia: demonstration of
      increased active transport, affinity, and increased glutamate level in intact red
      cells.
AB  - Sickle red blood cells (RBCs) have been shown to have an increase in total
      nicotinamide adenine dinucleotide (NAD) content by an as-yet-unknown mechanism.
      Because glutamine is an essential precursor in NAD biosynthesis, we have examined
      the rates of active RBC glutamine transport and glutamine transport kinetics with
      Michaelis-Menten constant (K[m]) and maximum velocity (V[max]) in RBCs from
      patients with sickle cell disease, patients with high reticulocyte counts, and
      normal volunteers. In addition, plasma and RBC levels of glutamine and glutamate
      in the three groups were analyzed. The rate of active glutamate transport in
      sickle RBCs increased threefold over that in high-reticulocyte RBCs and increased
      15-fold over that in normal RBCs. Glutamine transport K(m) in sickle RBCs was
      decreased fivefold in comparison with that in the high-reticulocyte group and
      that in normal control subjects. Glutamine transport V(max) for sickle RBCs was
      twofold and eightfold higher in comparison with those in the high-reticulocyte
      RBCs and normal control RBCs, respectively. Finally, the level of RBC glutamate
      (a byproduct of glutamine in NAD synthesis) in the sickle group was significantly
      increased in comparison with that in the high-reticulocyte group, whereas the RBC
      glutamine level was not. The higher glutamate level in sickle cells may suggest a
      higher glutamine turnover in these cells. These data suggest that sickle RBCs
      have an increased glutamine availability and affinity that may facilitate the
      increase in total NAD in sickle RBCs.

PMID- 9242371
TI  - Different CD3/T cell receptor monoclonal antibodies have distinct capacities to
      induce adhesion of T lymphocytes to endothelium.
AB  - Murine CD3/T cell receptor (TCR) monoclonal antibodies (mAbs) induce immediate
      peripheral lymphocytopenias of different degree and duration. Lymphocytopenia is
      of short duration after the administration of immunoglobulin A CD3 mAb, but it
      persists much longer after the administration of immunoglobulin G2a CD3 mAb.
      Peripheral lymphocytopenia after the administration of WT31, a murine
      immunoglobulin G1 TCR mAb, appears to be dependent on the polymorphism of
      Fc(gamma)RIIa. In high responders, lymphocytopenia is comparable to that observed
      after immunoglobulin G2a CD3 mAb; in low responders, no lymphocytopenia occurs.
      In vitro, both immunoglobulin A and immunoglobulin G2a CD3 mAbs induce immediate
      activation of CD11a/CD18, with concomitant up-regulation of CD11b/CD18 on T
      cells, each of which is shown to be involved in the concurrent adhesion of T
      cells to endothelium. WT31 induces an immediate activation of CD11a/CD18 as well
      as T cell adhesion to endothelium in Fc(gamma)RIIa high responders only,
      interestingly without changes in the level of expression of CD11b/CD18. We
      conclude that the immediate occurrence of peripheral lymphocytopenia after the
      administration of CD3/TCR mAb is mediated by changes in the level of expression
      or avidity (or both) of adhesion molecules on T cells, whereas the persistence of
      this lymphocytopenia depends on the isotype of the CD3/TCR mAb and on the
      presence of suitable Fc receptors.

PMID- 9242372
TI  - A surface swab method for culturing Foley catheters assays the pericatheter
      (urethral) but not the urine (luminal) microbial population.
AB  - Assessment of the urethral flora in patients with indwelling bladder catheters is
      problematic in the presence of urinary tract infection (UTI). A new surface swab
      method that samples the external catheter surface without interference from
      contaminated luminal contents is described. In vitro, recovery of adherent
      bacteria from the external catheter surface by the surface swab method was
      proportional to the bacterial density as measured by a comparison scrape method.
      In a prospective longitudinal assessment of three chronically catheterized
      subjects with polymicrobial catheter-associated UTI, a conventional roll plate
      catheter culture method suggested substantial overlap between the urethral and
      urine microbial populations, possibly a result of contamination of catheter
      cultures by infected urine. In contrast, the surface swab method revealed little
      overlap between these floras, evidence suggesting a predominantly luminal (rather
      than meatal) route of UTI acquisition. The new surface swab method should prove
      useful in future studies of the pathogenesis and prevention of catheter
      associated UTI.

PMID- 9242373
TI  - EGF induced SOS phosphorylation in PC12 cells involves P90 RSK-2.
AB  - SOS, the guanine nucleotide exchange factor for Ras, becomes phosphorylated on
      serine and threonine residues following stimulation of cells with growth factors.
      These phosphorylations may play a role in negative feedback of Ras stimulation
      and have been shown to be mediated in part by the MAP kinases Erk-1 and Erk-2.
      Here we show that in addition to MAP kinase, a major mitogen activated kinase for
      SOS is p90 Rsk-2, a downstream target of MAP kinase. p90 Rsk-2 phosphorylates SOS
      in an in gel assay and also in solution in vitro. The ability of p90 Rsk-2 to
      phosphorylate SOS increases greatly following EGF treatment of PC12 cells and is
      blocked by expression of N17 Ras or treatment with the MEK inhibitor PD98059.
      Phosphopeptide mapping revealed that the sites phosphorylated by p90 Rsk-2 in
      vitro were also phosphorylated in intact cells in response to EGF treatment.
      Several major sites of in vivo phosphorylation correlated with p90 Rsk-2
      phosphorylation sites rather than MAP kinase sites. It is therefore likely that
      p90 Rsk-2 plays an important role in the down regulation of the Ras activation
      pathway through SOS.

PMID- 9242374
TI  - Rb interacts with TAF(II)250/TFIID through multiple domains.
AB  - The retinoblastoma tumor suppressor gene product (Rb) binds directly to the
      largest TFIID subunit, TATA-binding protein associated factor TAF(II)250, first
      identified as the cell cycle regulatory protein CCG1. Here we map the domains in
      Rb and TAF(II)250 important for their interaction in vitro and in vivo. Both the
      amino terminus and the large pocket of Rb are able to associate independently
      with TAF(II)250. The binding domain(s) within the large pocket are distinct from
      the viral oncoprotein and E2F binding region since certain pocket mutations,
      which abolish E1A binding, do not abolish TAF(II)250 binding. Consistent with the
      large pocket of Rb binding to TAF(II)250, the large pocket domains of both p107
      and p130 are able to bind to TAF(II)250 in vivo. We also demonstrate that at
      least two regions of TAF(II)250 are able to bind to the large pocket of Rb
      independently whereas the amino terminus of Rb binds to a distinct domain in
      TAF(II)250. We further demonstrate that Rb can bind to TFIID in vitro, presumably
      in part through an interaction with TAF(II)250. Our results suggest a complex
      interaction between Rb and TAF(II)250 and imply that TAF(II)250, TFIID, and
      potentially other basal transcription factors are targets for regulation by Rb
      and Rb-related proteins.

PMID- 9242375
TI  - Oncogenic activation of RET by two distinct FMTC mutations affecting the tyrosine
      kinase domain.
AB  - Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid
      carcinoma (FMTC) are two dominantly inherited disorders caused by germline
      mutations of the RET proto-oncogene. The RET gene codes for a receptor tyrosine
      kinase. The majority of MEN2A and FMTC mutations are clustered in the extra
      cellular cysteine-rich domain and result in constitutive activation of the
      tyrosine kinase through the formation of disulfide-bonded RET homodimers.
      Recently, two novel point mutations have been identified in the germline of five
      distinct FMTC families. Both mutations occur within the catalytic domain of the
      RET kinase and lead to the substitution of either glutamic acid 768 or valine 804
      by an aspartic acid and a leucine respectively. We have introduced each FMTC
      mutation in two RET isoforms: RET51 the long isoform (1114 aa) and RET9 the short
      isoform (1072 aa) which differ in the C-terminal region of the protein. The RET51
      isoform carrying either E768D or V804L mutation was autophosphorylated, displayed
      a transforming activity upon expression in Rat1 fibroblasts and induced neuronal
      differentiation of PC12 cells. However, the transforming capacity of these RET51
      FMTC mutants was found to be severalfold less potent compared to the same isoform
      carrying either the MEN2A mutation (C634R) or the MEN2B mutation (M918T). In
      contrast, RET9 containing mutations E768D or V804L was not autophosphorylated,
      exhibited a poor oncogenic potential in fibroblasts and did not promote neuritic
      outgrowth upon expression in PC12 cells. Overall, these findings demonstrate that
      mutations E768D and V804L are gain-of-function mutations that confer to the long
      RET isoform the capacity to exert a biological effect, although these mutations
      are more weakly activating than the MEN2A and MEN2B mutations. These results may
      provide a biochemical basis as to why the phenotypic consequences of these
      mutations are restricted to thyroid C-cells.

PMID- 9242376
TI  - DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell
      lines: possible implications for role as tumor suppressor gene.
AB  - DAP-kinase is a novel calmodulin dependent serine/threonine kinase that carries
      ankyrin repeats and the death domain. It was recently isolated, by a functional
      selection approach of gene cloning, as a positive mediator of programmed cell
      death. In this study the expression of DAP-kinase was examined in the cell lines
      derived from various human neoplasms. DAP-kinase mRNA and protein expression were
      below the limit of detection in eight out of ten neoplastic derived B-cell lines.
      In six out of 14 examined bladder carcinoma, in three out of five renal cell
      carcinoma, and in four out of ten tested breast carcinoma cell lines, the DAP
      kinase protein levels were below detection limits or lower than 1% compared to
      the positive cell lines. Interestingly, DAP-kinase expression could be restored
      in some of the negative bladder carcinoma and B-cell lines by treatment of cells
      with 5'-azadeoxycytidine that causes DNA demethylation. The high frequency of
      loss of DAP-kinase expression in human tumor cell lines, and the occasional
      involvement of methylation in this process raise the possibility that this novel
      mediator of cell death may function as a tumor suppressor gene.

PMID- 9242377
TI  - Inhibition of epidermal growth factor receptor gene expression and function
      decreases proliferation of head and neck squamous carcinoma but not normal
      mucosal epithelial cells.
AB  - Previous reports have shown that fresh tissues and cell lines from patients with
      squamous cell carcinoma of the head and neck (SCCHN) overexpress transforming
      growth factor alpha (TGF-alpha) and its receptor, the epidermal growth factor
      receptor (EGFR) at both the mRNA and protein levels. Protein localization studies
      confirm that TGF-alpha and EGFR are produced by the same epithelial cells in
      tissues from head and neck cancer patients further supporting an autocrine growth
      pathway. Using three strategies, we examined the hypothesis that downmodulation
      of EGFR would reduce the proliferation of SCCHN cells. We targeted EGFR mRNA
      using antisense oligonucleotides and the mature EGFR protein at two sites, the
      ligand-binding domain and the kinase domain, and determined the effects of this
      targeting on SCCHN proliferation. Treatment of several SCCHN cell lines with a
      pair of antisense oligodeoxynucleotides directed against the translation start
      site and first intron-exon splice junction of the human EGFR gene resulted in
      decreased EGFR protein production and inhibited growth by 86% compared to a 13%
      reduction in cells treated with sense oligonucleotides (P=0.03). Growth
      inhibition was specific for carcinoma cells since the same EGFR antisense
      oligonucleotides had no effect on the proliferation of normal mucosa cells
      harvested from non-cancer patients. Two monoclonal antibodies which block ligand
      binding to EGFR (MAbs 425 and 528) inhibited the growth of several SCCHN cell
      lines by up to 97% which suggests that EGFR is participating in an autocrine
      pathway in SCCHN that is, at least in part, external. An EGFR-specific tyrosine
      kinase inhibitor (PD 153035) was found to inhibit EGFR phosphorylation in SCCHN
      cell lines and to reduce growth by 68% although it had no effect on the growth
      rate of normal mucosal epithelial cells. These experiments indicate that EGFR
      gene expression and function is critical for SCCHN cell growth but not for growth
      of normal mucosa cells and therefore may serve as a tumor-specific target for
      preventive and therapeutic strategies in head and neck cancer.

PMID- 9242378
TI  - Association of the Rho family small GTP-binding proteins with Rho GDP
      dissociation inhibitor (Rho GDI) in Saccharomyces cerevisiae.
AB  - The small GTP-binding proteins of the Rho family, consisting of the Rho, Rac, and
      Cdc42 subfamilies, are implicated in various cell functions, such as cell shape
      change, cell motility and cytokinesis, through reorganization of actin
      cytoskeleton. Rho GDI is a general regulator which forms a complex with the GDP
      bound inactive form of the Rho family members and inhibits their activation. We
      have purified Rho GDI from the yeast Saccharomyces cerevisiae, cloned its gene,
      and named it RDII (Rho GD). In this study, we have further characterized yeast
      Rho GDI. Rho GDI was found in the cytosol by immunoblot and immunofluorescence
      microscopic analyses. Rho1p and Cdc42p were co-immunoprecipitated with Rho GDI
      from the cytosol. This immunoprecipitated Rho1p was mainly bound to GDP. In the
      disruption mutant of Rho GDI, which did not show any apparent phenotype, both
      Rho1p and Cdc42p were also present in the cytosol. These results indicate that
      yeast Rho GDI possesses properties similar to those of mammalian Rho GDI, and
      that there is a cytosolic factor which functionally substitutes for Rho GDI in
      yeast.

PMID- 9242379
TI  - Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen
      independent growth and apoptosis.
AB  - Overexpression of many growth factor receptors, as well as growth factors, has
      been shown to confer varying degrees of estrogen-independent growth on estrogen
      receptor (ER) positive breast cancer cells. The proto-oncogene Raf-1 is a key
      intermediate in the signal transduction pathway of many of these growth factor
      receptors, and when constitutively activated in fibroblasts is transforming. To
      examine the effects of Raf-1 kinase activity on the estrogen-dependent growth of
      human breast cancer cells, ER + MCF-7 breast cancer cells were stably transfected
      with an expression construct directing the expression of an amino-truncated
      protein having constitutive kinase activity. Expression of constitutively
      activated Raf in MCF-7 cells is incompatible with growth in the presence of
      estrogen; that is, cells down-regulate expression of the transfected Raf.
      Constitutive Raf activity does allow for growth of the cells in the absence of
      estrogen, suggesting that activation of growth factor signaling pathways through
      Raf may confer a selective advantage for growth of breast cancer cells under
      estrogen-deprived conditions. In addition, the high levels of Raf activity induce
      apoptosis in cells grown under either condition. This is a novel activity for
      Raf, and may occur because the levels of the constitutive Raf are extremely high
      in these cells.

PMID- 9242380
TI  - Induction of vascular endothelial growth factor by nitric oxide in human
      glioblastoma and hepatocellular carcinoma cells.
AB  - We evaluated the effect of nitric oxide (NO) on vascular endothelial growth
      factor (VEGF) gene expression in human A-172 glioblastoma cells and human HepG2
      hepatocellular carcinoma cells. The mRNA level of VEGF increased in response to S
      Nitroso-N-acetyl-D,L-penicillamine (SNAP) in both cell lines, and increased in
      mRNA level well coincided with VEGF protein production in A-172 cells. SNAP at
      0.5 mM induced maximal stimulation of 4.4 and 3.7 kb VEGF mRNA expression after 6
      h about 11 and 8 fold increase, respectively above control level. Similar VEGF
      mRNA accumulation was observed also with NOR3, another chemical NO generator. To
      evaluate the effect of SNAP on VEGF mRNA stability, half-lives of VEGF mRNA were
      measured in A-172 cells cultured with or without 0.5 mM SNAP and treated with
      actinomycin D (25 microg/ml). Half-life for VEGF mRNA was found to be prolonged
      about 2.4 fold by SNAP. VEGF expression induced by SNAP was inhibited by
      guanylate cyclase inhibitors, methylene blue (10 microM) and LY-83583 (1 microM),
      and by the protein synthesis inhibitor, cycloheximide (25 microg/ml). These
      results suggest that induction of VEGF gene expression by NO is mediated through
      guanylate cyclase activity and requires on-going protein synthesis.

PMID- 9242381
TI  - Overexpression of wild type p70 S6 kinase interferes with cytokinesis.
AB  - p70 S6 kinase (p70s6k) is a serine/threonine kinase which is activated through an
      unidentified pathway by mitogenic stimuli. Here we demonstrate that stable- and
      transient-overexpression of wild type (WT)-p70s6k results in perturbation of
      cytokinesis in NIH3T3 cells. Cells overexpressing WT-p70s6k demonstrated a slow
      growth rate and lower viability, whereas cells overexpressing a mutant T229A
      p70s6k had a similar growth rate and viability as those of parental NIH3T3 cells.
      Moreover, WT-p70s6k cells demonstrated several abnormalities in cellular
      morphology; both the cytoplasm and the nuclei were large and a proportion of the
      cells was multinucleated. Flow cytometric analysis of propidium iodide-stained
      cells demonstrated that about 50% of the cells had 4N or greater content of DNA.
      When cell division in WT-p70s6k cells was monitored by time-lapse video
      microscopy, cytokines was often incomplete after mitosis, producing binucleated
      cells. Addition of rapamycin to WT-p70s6k cells, which inactivates endogenous and
      transfected p70s6k, failed to reverse any of the morphological abnormalities.
      These indicate that overexpression of p70s6k but not increases in activity of
      p70s6k, is responsible for the phenotype. A molecule which interacts with p70s6k
      may be involed in this regulation of cytokinesis.

PMID- 9242382
TI  - Cloning a novel member of the human interferon-inducible gene family associated
      with control of tumorigenicity in a model of human melanoma.
AB  - Chromosome 6-mediated suppression of tumorigenicity in malignant melanoma cell
      lines provides a model system to identify genes associated with the reversion of
      the tumorigenic phenotype. Using subtractive cDNA selection, we recently
      identified a series of novel genes which are differentially expressed in
      association with chromosome 6-mediated suppression. We now report the molecular
      characterization of a novel gene termed AIM2 for (Absent In Melanoma), which
      represents a 1485 bp cDNA. An open reading frame of 1032 base pairs,
      corresponding to 344 amino acid residues, is predicted. The predicted protein
      shares a conserved sequence domain of approximately 200 amino acids with known
      interferon-inducible genes of both human and mouse. We demonstrate that the AIM2
      gene encodes a transcript of approximately 2 kb which is expressed in spleen,
      small intestine, and peripheral blood leukocytes. In addition, we have localized
      AIM2 to the long arm of human chromosome 1 (band q22) in a highly conserved
      region which also contains the known interferon-inducible genes IFI16 and MNDA.
      We have also demonstrated that, like IFI16 and MNDA, AIM2 is induced in HL60
      cells by interferon gamma. Our findings support the existence of a family of
      genes in this region similar to the well-characterized mouse Ifi200 gene family.

PMID- 9242383
TI  - Identification of a core functional and structural domain of the v-Ski
      oncoprotein responsible for both transformation and myogenesis.
AB  - The v-ski oncogene promotes cellular transformation and myogenic differentiation.
      In quail embryo fibroblasts the two properties are displayed simultaneously and
      terminal muscle differentiation occurs only among cells already transformed by v
      ski. To understand how the two phenotypes are derived from a single gene, we have
      undertaken to identify functionally important regions in v-ski and to test
      whether these regions can promote one phenotype without the other. We have
      generated both random and targeted mutations in v-ski and evaluated the effects
      of these mutations on expression, intracellular location, transformation, and
      myogenesis. Among a total of 26 mutants analysed, we have not found complete
      separation of the myogenic and transforming properties. Mutations in the region
      of v-Ski encoded by exon 1 of c-ski frequently abolish both its transformation
      and muscle differentiation activities, whereas mutations outside of this region
      are always tolerated. When expressed in cells from a minigene containing only the
      exon 1 sequence, the protein displays the transforming and myogenic activities
      similar to v-Ski. These results argue that the amino acid sequence encoded by
      exon 1 contains the core functional domain of the oncoprotein. To determine
      whether this functional domain has a structural counterpart, we have fragmented
      the v-Ski protein by limited proteolysis and found a single proteolytically
      stable domain spanning the entire exon 1-encoded region. Physical studies of the
      polypeptide encoded by exon 1 confirms that it folds into a compact, globular
      protein. The finding that both the transforming and myogenic properties of v-Ski
      are inseparable by mutation and are contained in a single domain suggests that
      they are derived from the same function.

PMID- 9242384
TI  - An intron 1 enhancer element mediates oestrogen-induced suppression of ERBB2
      expression.
AB  - Overexpression of the ERBB2 gene in human breast cancer is associated with a poor
      prognosis and resistance to hormonal treatment and chemotherapy. Oestrogen
      receptor (ER) positive tumour-derived cell lines are known to express relatively
      low levels of ERBB2 protein under oestrogenic conditions, but markedly higher
      levels following withdrawal of oestrogens or administration of tamoxifen.
      Expression of the closely related ERBB3 gene, which co-operates with ERBB2 in
      cellular transformation, is now shown to respond to oestrogenic manipulation in a
      similar way, both responses being mediated largely by transcriptional changes.
      Six previously undescribed DNase I hypersensitive sites occur within the first
      intron of ERBB2 in cells that overexpress the gene. A 409 base pair DNA fragment
      containing one of these sites conferred ER dependent oestrogen inhibition on the
      ERBB2 promoter in two types of transient transfection assay. DNase I footprinting
      revealed four separate transcription factor binding sites within this fragment
      consistent with a role as a transcriptional enhancer. These findings implicate
      intron 1 sequences in the control of ERBB2 expression for the first time and
      demonstrate that one site within this region is involved in mediating the
      transcriptional response to oestrogens. Additionally, there is likely to be
      synergism between ERBB2 and ERBB3 signalling when both are overexpressed in
      response to oestrogen inhibition, thereby driving transformed cell behaviour.

PMID- 9242385
TI  - Avian winged helix proteins CWH-1, CWH-2 and CWH-3 repress transcription from Qin
      binding sites.
AB  - The chicken winged helix proteins, CWH-1, CWH-2 and CWH-3, were isolated and
      identified by homology cloning using the winged helix sequence of the retroviral
      oncogene qin as a probe. The CWH proteins act as growth stimulators in chicken
      embryo fibroblasts and in this activity resemble the Qin protein. Qin is a
      transcriptional regulator that functions as a repressor, and its oncogenic
      potential is correlated with the ability to repress transcription. In this
      communication we show that CWH proteins are localized in the cell nucleus,
      recognize the Qin DNA binding site and also function as transcriptional
      repressors. The repression activity of CWH-3 was mapped to the region of amino
      acids 211 to 311, a domain that is homologous to the major repression domain of
      Qin.

PMID- 9242386
TI  - Inhibition of in vitro proliferation of Epstein Barr Virus infected B cells by an
      antisense oligodeoxynucleotide targeted against EBV latent membrane protein LMP1.

PMID- 9242387
TI  - German truce on genome data access.

PMID- 9242388
TI  - 'Skewed medical goals' revealed by Indian survey.

PMID- 9242389
TI  - FDA seeks to close xenotransplant gap.

PMID- 9242390
TI  - University settles with patients over trade in 'stolen' embryos.

PMID- 9242391
TI  - US support for malaria research.

PMID- 9242392
TI  - EMBO fellows go home.

PMID- 9242393
TI  - Nightmare antibiotics.

PMID- 9242394
TI  - The democracy of the genes.

PMID- 9242395
TI  - Protein engineering. Reading, writing and redesigning.

PMID- 9242396
TI  - Cellular secretion. Now you see it, now you don't.

PMID- 9242397
TI  - Schizophrenia. The price of language?

PMID- 9242398
TI  - Neurobiology. Long-distance long-term depression.

PMID- 9242399
TI  - V(D)J recombination. From RAGs to stitches.

PMID- 9242401
TI  - Season of birth predicts mortality in rural Gambia.

PMID- 9242400
TI  - S-nitrosylation regulates apoptosis.

PMID- 9242402
TI  - Propagation of activity-dependent synaptic depression in simple neural networks.
AB  - Triple whole-cell recordings from simple networks of cultured hippocampal neurons
      show that Induction of long-term depression at glutamatergic synapses is
      accompanied by a back propagation of depression to Input synapses on the dendrite
      of the presynaptic neuron. The depression also propagates laterally to divergent
      outputs of the presynaptic neuron and to convergent inputs on the postsynaptic
      neuron. There is no forward propagation of depression to the output of the
      postsynaptic neuron and no presynaptic propagation accompanying long-term
      depression at GABAergic synapses. Activity-induced synaptic modification is
      therefore not restricted to the activated synapse, but selectively propagates
      throughout the neural network.

PMID- 9242403
TI  - The advantage of sex in evolving yeast populations.
AB  - Sex is a general feature of the life cycle of eukaryotes. It is not universal,
      however, as many organisms seem to lack sex entirely. The widespread occurrence
      of sex is puzzling, both because meiotic recombination can disrupt co-adapted
      combinations of genes, and because it halves the potential rate of reproduction
      in organisms with strongly differentiated male and female gametes. Most attempts
      to explain the maintenance of sexuality invoke differences between parents and
      sexual offspring. These differences may be advantageous in novel or changing
      environments if new gene combinations are favoured from time to time. Sex would
      then serve to concentrate beneficial mutations that have arisen independently
      into the same line of descent. But in a stable environment sex might serve to
      concentrate deleterious mutations, so that they will be more effectively purged
      from the population by selection. We have studied the effect of sex on mean
      fitness in experimental populations of the budding yeast Saccharomyces
      cerevisiae. Our results show that sex increases mean fitness in an environment to
      which the populations were well adapted, but not in an environment to which new
      adaptation occurred, supporting the hypothesis that the advantage of sexuality
      lay in the removal of deleterious mutations.

PMID- 9242404
TI  - The heritability of IQ.
AB  - IQ heritability, the portion of a population's IQ variability attributable to the
      effects of genes, has been investigated for nearly a century, yet it remains
      controversial. Covariance between relatives may be due not only to genes, but
      also to shared environments, and most previous models have assumed different
      degrees of similarity induced by environments specific to twins, to non-twin
      siblings (henceforth siblings), and to parents and offspring. We now evaluate an
      alternative model that replaces these three environments by two maternal womb
      environments, one for twins and another for siblings, along with a common home
      environment. Meta-analysis of 212 previous studies shows that our 'maternal
      effects' model fits the data better than the 'family-environments' model.
      Maternal effects, often assumed to be negligible, account for 20% of covariance
      between twins and 5% between siblings, and the effects of genes are
      correspondingly reduced, with two measures of heritability being less than 50%.
      The shared maternal environment may explain the striking correlation between the
      IQs of twins, especially those of adult twins that were reared apart. IQ
      heritability increases during early childhood, but whether it stabilizes
      thereafter remains unclear. A recent study of octogenarians, for instance,
      suggests that IQ heritability either remains constant through adolescence and
      adulthood, or continues to increase with age. Although the latter hypothesis has
      recently been endorsed, it gathers only modest statistical support in our
      analysis when compared to the maternal-effects hypothesis. Our analysis suggests
      that it will be important to understand the basis for these maternal effects if
      ways in which IQ might be increased are to be identified.

PMID- 9242405
TI  - Second-order fear conditioning prevented by blocking NMDA receptors in amygdala.
AB  - Antagonists of NMDA (N-methyl-D-aspartate)-type glutamate receptors disrupt
      several forms of learning. Although this might indicate that NMDA-receptor
      mediated processes are critical for synaptic plasticity, there may be other
      mechanisms by which NMDA-receptor antagonism could interfere with learning. For
      instance, fear conditioning would be blocked by microinfusion of the NMDA
      receptor antagonist AP5 (D,L-2-amino-5-phosphonovalerate) into the basolateral
      amygdala if AP5 inhibited routine synaptic transmission, thereby reducing the
      ability of stimuli to activate amygdala neurons. In second-order fear
      conditioning, the reinforcer is a fear-eliciting conditioned stimulus rather than
      an unconditioned stimulus. Expression of conditioned fear is amygdala-dependent
      and so provides a behavioural assessment of the ability of the reinforcer to
      activate amygdala neurons in the presence of AP5. We report here that intra
      amygdala AP5 actually enhances expression of conditioned fear to the conditioned
      stimulus that provides the reinforcement signal for second-order conditioning.
      Nevertheless, acquisition of second-order fear conditioning is completely
      blocked. Our findings strongly support the view that NMDA receptors are
      critically involved in synaptic plasticity.

PMID- 9242406
TI  - Transport, docking and exocytosis of single secretory granules in live chromaffin
      cells.
AB  - Neurons maintain a limited pool of synaptic vesicles which are docked at active
      zones and are awaiting exocytosis. By contrast, endocrine cells releasing large,
      dense-core secretory granules have no active zones, and there is disagreement
      about the size and even the existence of the docked pool. It is not known how,
      and how rapidly, secretory vesicles are replaced at exocytic sites in either
      neurons or endocrine cells. By using electron microscopy, we have now been able
      to identify a pool of docked granules in chromaffin cells that is selectively
      depleted when cells secrete. With evanescent-wave fluorescence microscopy, we
      observed single granules undergoing exocytosis and leaving behind patches of bare
      plasmalemma. Fresh granules travelled to the plasmalemma at a top speed of 114 nm
      s(-1), taking an average of 6 min to arrive. On arrival, their motility
      diminished 4-fold, probably as a result of docking. Some granules detached and
      returned to the cytosol. We conclude that a large pool of docked granules turns
      over slowly, that granules move actively to their docking sites, that docking is
      reversible, and that the 'rapidly releasable pool' measured
      electrophysiologically represents a small subset of docked granules.

PMID- 9242407
TI  - Optical detection of a quantal presynaptic membrane turnover.
AB  - Exploration of the mechanisms and plasticity of synaptic transmission has been
      hindered by the lack of a method to measure single vesicle turnover directly in
      individual presynaptic boutons at isolated nerve terminals. Although postsynaptic
      electrical recordings have provided a wealth of invaluable basic information
      about quantal presynaptic processes, this approach has often proved difficult to
      apply at most central nervous system synapses. Here we describe the direct
      optical detection of single quantal events in individual presynaptic boutons of
      cultured hippocampal neurons. Using the fluorescent dye FM 1-43 as a tracer for
      presynaptic endocytosis, we have characterized both evoked and spontaneous
      components of presynaptic function at the level of individual quanta. Our results
      are consistent with quantal interpretations of previous electrophysiological
      analyses and provide new information about the unitary membrane recycling event
      and its coupling to individual action potential stimuli, about spontaneous
      vesicle turnover at individual boutons, and about the numbers of vesicles
      recycling at individual boutons.

PMID- 9242408
TI  - Cloning and characterization of a mammalian proton-coupled metal-ion transporter.
AB  - Metal ions are essential cofactors for a wealth of biological processes,
      including oxidative phosphorylation, gene regulation and free-radical
      homeostasis. Failure to maintain appropriate levels of metal ions in humans is a
      feature of hereditary haemochromatosis, disorders of metal-ion deficiency, and
      certain neurodegenerative diseases. Despite their pivotal physiological roles,
      however, there is no molecular information on how metal ions are actively
      absorbed by mammalian cells. We have now identified a new metal-ion transporter
      in the rat, DCT1, which has an unusually broad substrate range that includes
      Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+. DCT1 mediates active transport
      that is proton-coupled and depends on the cell membrane potential. It is a 561
      amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously
      expressed, most notably in the proximal duodenum. DCT1 is upregulated by dietary
      iron deficiency, and may represent a key mediator of intestinal iron absorption.
      DCT1 is a member of the 'natural-resistance-associated macrophage protein'
      (Nramp) family and thus its properties provide insight into how these proteins
      confer resistance to pathogens.

PMID- 9242409
TI  - Cell-free V(D)J recombination.
AB  - V(D)J recombination generates diversity in the immune system through the lymphoid
      specific assembly of multiple gene segments into functional immunoglobulin and T
      cell receptor genes. The first step in V(D)J recombination is cleavage of DNA at
      recombination signal sequences. Cleavage produces a blunt DNA end on each signal
      sequence and a hairpin end on adjacent coding gene segments, and can be
      reproduced in vitro by using purified RAG and RAG2 proteins. The later steps
      involve processing and joining of the cleaved DNA ends, and until now have been
      studied only in cells. Here we reconstitute the complete V(D)J recombination
      reaction in a cell-free system. We find that the RAG proteins are not only
      involved in cleavage, but are also needed in the later steps for efficient
      joining of coding ends. Joining is largely directed by short pieces of identical
      sequence in the coding flanks, but addition of human DNA ligase I results in
      greater diversity. Coding junctions contain short deletions as well as additions
      complementary to a coding flank (P nucleotides). Addition of non-templated
      nucleotides into coding junctions is mediated by terminal deoxyribonucleotidyl
      transferase. The cell-free reaction can therefore reproduce the complete set of
      processing events that occur in cells.

PMID- 9242410
TI  - Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in
      mammalian cells.
AB  - Mutation of the XRCC4 gene in mammalian cells prevents the formation of the
      signal and coding joints in the V(D)J recombination reaction, which is necessary
      for production of a functional immunoglobulin gene, and renders the cells highly
      sensitive to ionizing radiation. However, XRCC4 shares no sequence homology with
      other proteins, nor does it have a biochemical activity to indicate what its
      function might be. Here we show that DNA ligase IV co-immunoprecipitates with
      XRCC4 and that these two proteins specifically interact with one another in a
      yeast two-hybrid system. Ligation of DNA double-strand breaks in a cell-free
      system by DNA ligase IV is increased fivefold by purified XRCC4 and seven- to
      eightfold when XRCC4 is co-expressed with DNA ligase IV. We conclude that the
      biological consequences of mutating XRCC4 are primarily due to the loss of its
      stimulatory effect on DNA ligase IV: the function of the XRCC4-DNA ligase IV
      complex may be to carry out the final steps of V(D)J recombination and joining of
      DNA ends.

PMID- 9242411
TI  - Yeast DNA ligase IV mediates non-homologous DNA end joining.
AB  - The discovery of homologues from the yeast Saccharomyces cerevisiae of the human
      Ku DNA-end-binding proteins (HDF1 and KU80) has established that this organism is
      capable of non-homologous double-strand end joining (NHEJ), a form of DNA double
      strand break repair (DSBR) active in mammalian V(D)J recombination.
      Identification of the DNA ligase that mediates NHEJ in yeast will help elucidate
      the function of the four mammalian DNA ligases in DSBR, V(D)J recombination and
      other reactions. Here we show that S. cerevisiae has two typical DNA ligases, the
      known DNA ligase I homologue CDC9 and the previously unknown DNA ligase IV
      homologue DNL4. dnl4 mutants are deficient in precise and end-processed NHEJ.
      DNL4 and HDF1 are epistatic in this regard, with the mutation of each having
      equivalent effects. dnl4 mutants are complemented by overexpression of Dnl4 but
      not of Cdc9, and deficiency of Dnl4 alone does not impair either cell growth or
      the Cdc9-mediated responses to ionizing and ultraviolet radiation. Thus, S.
      cerevisiae has two distinct and separate ligation pathways.

PMID- 9242412
TI  - Developmental expression of BPAG1-n: insights into the spastic ataxia and gross
      neurologic degeneration in dystonia musculorum mice.
AB  - Ablation of the BPAG1 gene results in the dystonia musculorum mouse, exhibiting
      rapid spinal nerve degeneration, dystonic movements, and severe ataxia. By
      defining the developmental and tissue-specific expression of the neuronal form of
      BPAG1 (BPAG1-n) and by comparing the corresponding pathology in BPAG1 null mice,
      we seek here to understand how absence of BPAG1 results in this devastating
      phenotype in mice and in potentially related human neurological disorders.
      Throughout normal development, BPAG1-n was expressed in a variety of sensory and
      autonomic neuronal structures, but was absent or reduced in areas such as basal
      ganglia that are often affected in dystonias and ataxias. Interestingly, BPAG1-n
      was also expressed broadly in embryonic motor neurons, but expression declined
      dramatically after birth. Despite these complex developmental patterns, BPAG1-/-
      pathology was restricted largely to postnatal development. Moreover, gross
      neuronal degeneration was restricted to only a few regions where BPAG1-n was
      found, including dorsal root ganglion neurons and a small subset of motor
      neurons. Most notably, while skeletal muscle was normal, appearance of severe
      dystonic ataxia correlated with postnatal degeneration of muscle spindles.
      Collectively, our findings suggest a mechanism for the BPAG1 null phenotype and
      indicate that different neurons respond differently to the absence of BPAG1-n, a
      cytoskeletal linker protein.

PMID- 9242413
TI  - Xenopus laevis sperm-egg adhesion is regulated by modifications in the sperm
      receptor and the egg vitelline envelope.
AB  - The biochemical and ultrastructural changes in the envelope of the Xenopus laevis
      egg that occur during oviposition and fertilization have been thoroughly studied
      (Hedrick, J. L., and Nishihara, D. M., Methods Cell Biol. 36, 231-247, 1991;
      Larabell, C. A., and Chandler, D. E., J. Electron Microsc. Tech. 17, 294-318,
      1991). However, the biological significance of these changes with respect to
      gamete interaction has been unclear. In the current study, it was found that
      changes in the envelope are directly responsible for regulating sperm-egg
      adhesion, an initial step of fertilization. As a result of these transformations,
      sperm bind only to unfertilized oviposited eggs, not to oocytes or coelomic eggs.
      In addition, they do not bind to fertilized eggs. The molecular and cellular
      basis of the regulation of the sperm binding process was investigated in the
      context of our recent findings that two structurally related envelope
      glycoproteins, gp69/64, serve as sperm receptors during fertilization (Tian, J.
      D., Gong, H., Thomsen, G. H., and Lennarz, W. J., J. Cell Biol. 136, 1099-1108,
      1997). Although the purified gp69/64 glycoproteins isolated from the oocyte or
      coelomic egg envelopes exhibited sperm binding activity, when these proteins are
      part of the intact oocyte or coelomic egg envelopes, they are not accessible to
      either anti-gp69/64 antibodies or to sperm. During the conversion from the
      coelomic to the vitelline envelope, the gp69/64 sperm receptors become exposed on
      the surface, an event that correlates with proteolytic cleavage of gp43 and
      accompanying ultrastructural alterations in the envelope. Conversely, after
      fertilization, when the vitelline envelope of the egg is converted to the
      fertilization envelope of the zygote, limited proteolytic cleavage of the sperm
      receptor results in loss of sperm binding activity. In addition, formation of a
      fertilization layer on top of the structurally altered VE adds another physical
      block to sperm binding. These results provide new insights into structure
      function relationships between envelope components of the anuran egg, and provide
      further evidence supporting the key role of gp69/64 as sperm receptors during X.
      laevis fertilization.

PMID- 9242414
TI  - Genetic interactions in zebrafish midline development.
AB  - Mutational analyses have shown that the genes no tail (ntl, Brachyury homolog),
      floating head (flh, a Not homeobox gene), and cyclops (cyc) play direct and
      essential roles in the development of midline structures in the zebrafish. In
      both ntl and flh mutants a notochord does not develop, and in cyc mutants the
      floor plate is nearly entirely missing. We made double mutants to learn how these
      genes might interact. Midline development is disrupted to a greater extent in
      cyc;flh double mutants than in either cyc or flh single mutants; their effects
      appear additive. Both the notochord and floor plate are completely lacking, and
      other phenotypic disturbances suggest that midline signaling functions are
      severely reduced. On the other hand, trunk midline defects in flh;ntl double
      mutants are not additive, but are most often similar to those in ntl single
      mutants. This finding reveals that loss of ntl function can suppress phenotypic
      defects due to mutation at flh, and we interpret it to mean that the wild-type
      allele of ntl (ntl+) functions upstream to flh in a regulatory hierarchy. Loss of
      function of ntl also strongly suppresses the floor plate deficiency in cyc
      mutants, for we found trunk floor plate to be present in cyc;ntl double mutants.
      From these findings we propose that ntl+ plays an early role in cell fate choice
      at the dorsal midline, mediated by the Ntl protein acting to antagonize floor
      plate development as well as to promote notochord development.

PMID- 9242415
TI  - Temporal separation in the specification of primary and secondary motoneurons in
      zebrafish.
AB  - In zebrafish there are two populations of motoneurons, primary and secondary,
      that are temporally separate in their development. To determine if midline cells
      play a role in the specification of these neurons, we analyzed both secondary and
      primary motoneurons in mutants lacking floor plate, notochord, or both floor
      plate and notochord. Our data show that the specification of secondary
      motoneurons, those most similar to motoneurons in birds and mammals, depends on
      the presence of either a differentiated floor plate or notochord. In the absence
      of both of these structures, secondary motoneurons fail to form. In contrast,
      primary motoneurons, early developing motoneurons found in fish and amphibians,
      can develop in the absence of both floor plate and notochord. A spatial
      correspondence is found between secondary motoneurons and sonic hedgehog
      expressing floor plate and notochord. In contrast, primary motoneuronal
      specification depends on the presence of sonic hedgehog in gastrula axial
      mesoderm, the tissue that will give rise to the notochord. These results suggest
      that both primary and secondary motoneurons are specified by signals from midline
      tissues, but at very different stages of embryonic development.

PMID- 9242416
TI  - Embryonic and fetal myogenic programs act through separate enhancers at the
      MLC1F/3F locus.
AB  - Embryonic and fetal stages of skeletal muscle development are characterized by
      the differential expression of a number of muscle-specific genes. These include
      the products of independent promoters at the fast myosin light chain 1F/3F locus.
      In the mouse embryo MLC1F transcripts accumulate in embryonic skeletal muscle
      from E9, 4-5 days before high-level accumulation of MLC3F transcripts. A 3'
      enhancer can activate MLC1F and MLC3F promoters in differentiated muscle cells in
      vitro and in transgenic mice; both promoters, however, are activated at the time
      of MLC1F transcript accumulation. We now demonstrate the presence of a second
      muscle-specific enhancer at this locus, located in the intron separating the
      MLC1F and MLC3F promoters. Transgenic mice containing the intronic, but lacking
      the 3' enhancer, express high levels of an nlacZ reporter gene from the MLC3F
      promoter in adult fast skeletal muscle fibers. In contrast to the 3' enhancer,
      the intronic element is inactive both in embryonic muscle cells in vivo and in
      embryonic myocyte cultures. The intronic enhancer is activated at the onset of
      fetal development in both primary and secondary muscle fibers, at the time of
      endogenous MLC3F transcript accumulation. Late-activated MLC3F transgenes thus
      provide a novel in toto marker of fetal myogenesis. These results suggest that
      temporal regulation of transcription at the MLC1F/3F locus is controlled by
      separate enhancers which are differentially activated during embryonic and fetal
      development.

PMID- 9242417
TI  - Mapping sperm binding domains on the sea urchin egg receptor for sperm.
AB  - The receptor on the surface of the egg of the sea urchin Strongylocentrotus
      purpuratus that mediates species-specific binding of sperm is a 350-kDa cell
      surface glycoprotein. Earlier studies established that a recombinant protein
      encompassing a major portion of the N-terminal half of the receptor inhibited
      fertilization when tested in a competitive fertilization bioassay. To identify in
      more detail the sites in this domain of the receptor that are involved in binding
      sperm, a series of deletion constructs were expressed as glutathione S
      transferase fusion proteins and tested for inhibitory activity in a fertilization
      bioassay. In addition, a novel assay for directly testing the sperm binding
      activity of these proteins was developed. In this assay we quantitated sperm
      binding to recombinant proteins representing various domains of the receptor
      immobilized on glutathione agarose beads. Using this new assay, two domains in
      the N-terminal half of the receptor were found to be involved in sperm binding.
      One of the peptide domains, composed of 247 amino acids, binds both the sperm of
      S. purpuratus and the sperm of another genus of sea urchin, Lytechinus pictus. In
      contrast, binding to the second domain consisting of a 32-amino-acid residue
      peptide was found to be genus specific; no binding of L. pictus sperm was
      observed. A working model is proposed incorporating these findings with earlier
      studies on the function of the oligosaccharide chains of the receptor. In this
      model it is postulated that the sperm initially interact with the nonspecific
      binding domain on the polypeptide and the sulfated O-linked oligosaccharide
      chains of the receptor. This interaction is followed by binding to the more
      specific polypeptide binding site on the receptor. It is proposed that only
      subsequent to binding at this second site can gamete fusion occur.

PMID- 9242418
TI  - Dorsal-ventral patterning during neural induction in Xenopus: assessment of
      spinal cord regionalization with xHB9, a marker for the motor neuron region.
AB  - While the role of the notochord and floor plate in patterning the dorsal-ventral
      (D/V) axis of the neural tube is clearly established, relatively little is known
      about the earliest stages of D/V regionalization. In an effort to examine more
      closely the initial, preneural plate stages of regionalization along the
      prospective D/V neural axis, we have performed a series of explant experiments
      employing xHB9, a novel marker of the motor neuron region in Xenopus. Using
      tissue recombinants and Keller explants we show that direct mesodermal contact is
      both necessary and sufficient for the initial induction of xHB9 in the motor
      neuron region. We also show that presumptive neural plate explants removed as
      early as midgastrulation and cultured in isolation are already specified to
      express xHB9 but do so in an inappropriate spatial pattern while identical
      explants are specified to express the floor plate marker vhh-1 with correct
      spatial patterning. Our data suggest that, in addition to floor plate signaling,
      continued interactions with the underlying mesoderm through neural tube stages
      are essential for proper spatial patterning of the motor neuron region.

PMID- 9242419
TI  - Inhibition of morphogenetic movement during Xenopus gastrulation by injected
      sulfatase: implications for anteroposterior and dorsoventral axis formation.
AB  - In order to explore the role of morphogenetic movement in the establishment of
      anteroposterior and dorsoventral axes, we sought to identify novel in vivo
      inhibitors of gastrulation movements in Xenopus laevis. Injection of hydrolytic
      sulfatase into the blastocoels of gastrula stage embryos resulted in severe
      anteroposterior truncation, without a corresponding truncation of the
      dorsoventral axis. Confocal microscopy of whole embryos revealed that
      gastrulation movements are severely disrupted by sulfatase; in addition,
      sulfatase dramatically inhibited chordomesodermal cell elongation and convergent
      extension movements in planar dorsal marginal zone explants. The phenotype of
      anteroposterior reduction elicited by sulfatase is distinctly different from
      commonly generated dorsoanterior phenotypes (e.g., ultraviolet irradiation of the
      vegetal cortex prior to cortical rotation or suramin injection), and the two
      varieties of phenotype appear to result from inhibition of distinct, separable
      components of the axis-generating machinery.

PMID- 9242420
TI  - LiCl perturbs ectodermal veg1 lineage allocations in Strongylocentrotus
      purpuratus embryos.
AB  - In normal development the veg1 tier of the sixth cleavage Strongylocentrotus
      purpuratus embryo contributes progeny to both ectodermal lineages and portions of
      the archenteron. Treatment with 18 mM LiCl specifically affects this lineage
      allocation, reducing or eliminating the veg1 contribution to ectoderm. Less
      frequently this concentration of lithium causes the progeny of animal blastomeres
      to contribute to the archenteron.

PMID- 9242421
TI  - Neural tube is partially dorsalized by overexpression of HrPax-37: the ascidian
      homologue of Pax-3 and Pax-7.
AB  - The origin and elaboration of the central nervous system played an important role
      in chordate and vertebrate history. All chordates possess a dorsal tubular
      central nervous system, but elaboration of dorsoventral and segmental pattern is
      far more pronounced in cephalochordates and vertebrates than in the more basal
      urochordates. Analysis of the urochordates, therefore, should allow deduction of
      the neural organization and neuronal patterning mechanisms that predated overt
      dorsoventral and segmental complexity. Here we report functional studies of the
      ascidian Pax gene (HrPax-37). The spatiotemporal expression pattern of HrPax-37
      has suggested involvement in two distinct developmental processes: specification
      of dorsal cell fates of ectoderm during neurulation, and regional differentiation
      of the neural tube in later stages. Here we show that HrPax-37 is descendent from
      the precursor of the Pax-3 and Pax-7 genes implicated in specification of dorsal
      fate in the vertebrate neural tube. We also demonstrate that injection of HrPax
      37 RNA into fertilized eggs causes ectopic expression of the dorsal neural marker
      tyrosinase gene in neurulae, confirming a regulatory role in dorsal patterning of
      the neural tube comparable to its vertebrate homologues. These results suggest
      that dorsal specification in the neural tube by Pax-3/7 subfamily genes was
      established in the ancestors of extant chordates during emergence of the dorsal
      tubular nervous system.

PMID- 9242422
TI  - Two Otx proteins generated from multiple transcripts of a single gene in
      Strongylocentrotus purpuratus.
AB  - Orthodenticle-related (Otx) proteins are a highly conserved class of homeobox
      containing transcription factors found in a wide range of organisms. They
      function in numerous developmental events, most prominently, anterior head
      patterning in insects and vertebrates. In the sea urchin, Strongylocentrotus
      purpuratus, an orthodenticle-related protein called SpOtx is believed to direct
      the activation of the aboral ectoderm-specific Spec2a gene and more generally the
      differentiation of aboral ectoderm cells. To learn more about the structure,
      expression, and function of SpOtx and compare its properties with those of
      orthologs from other species, we isolated cDNA and genomic clones containing
      SpOtx sequences. Here, we report that SpOtx exists in two forms (alpha and beta)
      that are generated by alternative RNA splicing from a single SpOtx gene.
      SpOtx(alpha) and SpOtx(beta) had identical C-termini and homeoboxes but were
      entirely different in their N-terminal domains. SpOtx(alpha) mRNAs were
      transcribed from a single start site and accumulated in all cells during
      cleavage, but were gradually concentrated in oral ectoderm and vegetal plate
      territories during gastrulation. In contrast, three distinct SpOtx(beta) mRNAs
      resulted from two separate transcriptional initiation events, and these
      transcripts began to accumulate at mesenchyme blastula stage primarily in
      ectoderm and then later were largely restricted to oral ectoderm and vegetal
      plate territories. DNA-binding activity for SpOtx(beta) appeared later in
      development than SpOtx(alpha). Overexpression of SpOtx(alpha) and SpOtx(beta)
      induced in sea urchin embryos by mRNA injection demonstrated that SpOtx(alpha)
      was able to repress the accumulation of SpOtx(beta) transcripts, whereas
      SpOtx(beta) had no effect on the accumulation of SpOtx(alpha) transcripts. These
      results demonstrate that novel forms of Otx are produced in sea urchins by
      differential promoter utilization and alternative splicing. It may be that
      similar regulatory mechanisms lead to diverse forms of Otx in vertebrates.

PMID- 9242423
TI  - Relationships between protein isoforms and genetic functions demonstrate
      functional redundancy at the Broad-Complex during Drosophila metamorphosis.
AB  - Metamorphosis in holometabolous insects is an ecdysone-dependent process by which
      the larval form is replaced by a reproductive, adult form. At the onset of
      metamorphosis ecdysone induces a set of early genes which coordinate tissue
      specific responses to hormone. The Broad-Complex (BR-C) early gene, which acts as
      a global regulator of tissue-specific responses to ecdysone, encodes a family of
      zinc-finger DNA binding proteins known as Z1, Z2, Z3, and Z4. Genetically the BR
      C encodes three complementing functions, br, rbp, and 2Bc, and a class of npr1
      alleles that fail to complement any of the other genetic functions. The effects
      of BR-C mutations on metamorphic development are highly pleiotropic, yet little
      is known about the roles of individual BR-C proteins in directing the required
      responses to ecdysone. Because the BR-C is a vital regulator of metamorphosis it
      is essential to establish the relationships between BR-C genetic functions and
      protein products. We present here the first general and definitive study of these
      relationships. Using heat-inducible transgenes we have rescued lethality
      associated with each of the complementing genetic functions and have restored
      transcriptional activity of tissue-specific BR-C(+)-dependent target genes. Our
      data lead us to conclude that br+ function is only provided by the Z2 isoform. We
      find that Z1 transgenes provide full rbp+ function, while Z4 provides partial
      function. Likewise, while Z3 provides full 2Bc+ function, Z2 also provides
      partial function. These results indicate possible functional redundancy or
      regulatory dependence (via autoregulation) associated with the rbp+ and 2Bc+
      functions. The establishment of these relationships between BR-C genetic
      functions and protein isoforms is an important step toward understanding the
      roles of BR-C proteins in directing metamorphic responses to ecdysone.

PMID- 9242424
TI  - Postembryonic development of the midline glia in the CNS of Drosophila:
      proliferation, programmed cell death, and endocrine regulation.
AB  - The development of Drosophila midline glia during larval and pupal stages was
      characterized by localizing beta-gal expression in enhancer trap lines, as well
      as with BrdU incorporation and pulse-chase experiments. At hatching about 40 to
      50 glial cells are present along the midline of the ventral nerve cord (2 to 3
      dorsal and 1 to 2 ventral cells per neuromere). The cells proliferate during the
      third larval instar and spread dorsoventrally within the midline, increasing in
      number to about 230 or more (around 20 cells per neuromere). Cell divisions cease
      shortly after pupariation, and the cells persist for the first half of pupal life
      with no apparent changes in numbers or positions. Between 50 and 80% of
      metamorphosis, however, virtually all of the midline glia undergo programmed cell
      death. Tissue culture experiments indicate that the peak of ecdysteroids
      occurring at pupariation is required for the cessation of proliferation of
      midline glia and their subsequent degeneration. Midline glia in central nervous
      systems (CNS) cultured with low or no ecdysteroids survive and continue to
      divide, whereas they cease proliferating and later degenerate with high
      ecdysteroids levels. The midline glial may play a role during CNS metamorphosis
      similar to that of their progenitors in the embryo, in stabilizing outgrowing
      neurites that cross or run along the midline.

PMID- 9242425
TI  - A role for Indian hedgehog in extraembryonic endoderm differentiation in F9 cells
      and the early mouse embryo.
AB  - Hedgehog genes in Drosophila and vertebrates control patterning of a number of
      different structures during embryogenesis. They code for secreted signaling
      proteins that are cleaved into an active aminopeptide and a carboxypeptide. The
      aminopeptide can mediate local and long range events and can act as a morphogen,
      inducing differentiation of distinct cell types in a concentration-dependent
      manner. We demonstrate here that the expression of Indian hedgehog mRNA and
      protein is upregulated dramatically as F9 cells differentiate in response to
      retinoic acid, into either parietal endoderm or embryoid bodies, containing an
      outer visceral endoderm layer. The ES cell line D3 forms embryoid bodies in
      suspension culture without addition of retinoic acid and also upregulates Indian
      hedgehog expression. RT-PCR analysis of blastocyst outgrowth cultures
      demonstrates that whereas little or no Indian hedgehog message is present in
      blastocysts, significant levels appear upon subsequent days of culture,
      coincident with the emergence of parietal endoderm cells. In situ hybridization
      analysis for Indian hedgehog mRNA expression demonstrates the presence of
      elevated levels of message in the outer visceral endoderm cells relative to the
      core cells in mature embryoid bodies and in the visceral endoderm of Day 6.5
      embryos. Whole-mount in situ hybridization analysis of Day 7.5 and 8.5 embryos
      indicates that Indian hedgehog expression is highest in the visceral yolk sac at
      this stage. F9 cell lines expressing a full length Indian hedgehog cDNA express a
      number of characteristics of differentiated cells, in the absence of retinoic
      acid. Taken together, these data suggest that Indian hedgehog is involved in
      mediating differentiation of extraembryonic endoderm during early mouse
      embryogenesis.

PMID- 9242426
TI  - Evidence for serum response factor-mediated regulatory networks governing
      SM22alpha transcription in smooth, skeletal, and cardiac muscle cells.
AB  - SM22alpha is an adult smooth muscle-specific protein that is expressed in the
      smooth, cardiac, and skeletal muscle lineages during early embryogenesis before
      becoming restricted specifically to all vascular and visceral smooth muscle cells
      (SMC) in late fetal development and adulthood. We have used the SM22alpha gene as
      a marker to define the regulatory mechanisms that control muscle-specific gene
      expression in SMCs. Previously, we reported that the 445-base-pair promoter of
      SM22alpha was sufficient to direct transcription of a lacZ reporter gene in early
      cardiac and skeletal muscle cell lineages and in a subset of arterial SMCs, but
      not in venous nor visceral SMCs in transgenic mice. Here we describe two
      evolutionarily conserved CArG (CC(A/T)6GG) boxes in the SM22alpha promoter, both
      of which are essential for full promoter activity in cultured SMCs. In contrast,
      only the promoter-proximal CArG box is essential for specific expression in
      developing smooth, skeletal, and cardiac muscle lineages in transgenic mice. Both
      CArG boxes bind serum response factor (SRF), but SRF binding is not sufficient
      for SM22alpha promoter activity, since overexpression of SRF in the embryonal
      teratocarcinoma cell line F9, which normally expresses low levels of SRF, fails
      to activate the promoter. However, a chimeric protein in which SRF was fused to
      the transcription activation domain of the viral coactivator VP16 is able to
      activate the SM22alpha promoter in F9 cells. These results demonstrate the
      SM22alpha promoter-proximal CArG box is a target for the regulatory programs that
      confer smooth, skeletal, and cardiac muscle specificity to the SM22alpha promoter
      and they suggest that SRF activates SM22alpha transcription in conjunction with
      additional regulatory factors that are cell type-restricted.

PMID- 9242427
TI  - MCF-7: the first hormone-responsive breast cancer cell line.

PMID- 9242428
TI  - Insulin-like growth factor-I receptor overexpression mediates cellular
      radioresistance and local breast cancer recurrence after lumpectomy and
      radiation.
AB  - The insulin-like growth factor-I receptor (IGF-IR) plays a critical role in cell
      growth regulation and transformation. The radiosensitivity of NIH 3T3 fibroblasts
      overexpressing either wild-type or mutant IGF-IR was examined. High levels of
      wild-type IGF-IR conferred radioresistance, and mutational analysis revealed that
      this effect correlated with the transforming capacity but not the mitogenic
      activity of the receptor. The radioresistant phenotype was reversed when the
      cells were incubated with antisense oligonucleotides targeted to IGF-IR mRNA,
      demonstrating that IGF-IR directly influences radioresistance. The clinical
      significance of these findings was examined in an immunohistochemical analysis of
      primary breast tumors, revealing that high levels of IGF-IR in tumor samples were
      highly correlated with ipsilateral breast tumor recurrence (IBTR) following
      lumpectomy and radiation therapy (P = 0.001). Subgroup analysis revealed that,
      for early breast tumor relapses (within 4 years of initial breast tumor
      diagnosis), elevated levels of IGF-IR were strongly associated with IBTR (P =
      0.004) but IGF-IR expression was not prognostic for IBTR from breast cancer
      patients with late relapses (P was not significant). These studies provide
      evidence for the influence of IGF-IR on cellular radioresistance and response to
      therapy and raise the possibility that the radiocurability of selected tumors may
      be improved by pharmaceutical strategies directed toward the IGF-IR.

PMID- 9242429
TI  - Antitumor activity of the novel human breast cancer growth inhibitor, mammary
      derived growth inhibitor-related gene, MRG.
AB  - A novel human tumor growth inhibitor was identified by differential cDNA
      sequencing. The predicted amino acid sequence of this tumor-suppressing factor
      has a significant sequence homology to mouse mammary-derived growth inhibitor and
      thus was named mammary-derived growth inhibitor-related gene (MRG). MRG was found
      to be expressed in normal and benign human breast tissues but not in breast
      carcinomas. In situ hybridization analysis demonstrated a stage-specific MRG
      expression as follows. MRG was barely detectable in breast carcinomas, showed
      partial and weak expression in benign hyperplasia, but was expressed at a high
      level in normal breast epithelial cells. To determine if MRG can modulate in vivo
      growth of human breast cancers, we transfected a full-length MRG cDNA into MDA-MB
      231 human breast cancer cells and studied the orthotopic growth of MRG
      transfectants versus control transfectants in the mammary fat pad of athymic nude
      mice. Overexpression of MRG in human breast cancer cells significantly suppressed
      cell proliferation in vitro and tumor growth in an orthotopic nude mouse model.
      These results suggest that MRG has tumor-suppressing activity, and the loss of
      MRG expression may be involved in the development and progression of breast
      cancer.

PMID- 9242430
TI  - Histo-blood group A/B versus H status of human carcinoma cells as correlated with
      haptotactic cell motility: approach with A and B gene transfection.
AB  - In a search for the molecular basis of ABH status of tumors as correlated with
      malignancy, we studied various malignancy-related phenotypes of high H/Le(y)
      expressing tumor cell lines in comparison with phenotypes of the same lines
      transfected with histo-blood group A or B genes. A and B gene transfectants,
      prepared independently from different H-active parental cells, showed A or B
      activity and abolition of H activity. All A and B gene transfectants, regardless
      of source, were characterized by significantly reduced Matrigel-dependent
      haptotactic motility. The level of haptotaxis of all transfectants was similar to
      that of parental cells in the presence of antibodies against human integrin
      subunits alpha3, alpha6, or beta1. These subunits showed high expression of A or
      B epitope in the A and B gene transfectants. Enhancement versus reduction of
      malignancy, associated with deletion versus induction of A/B epitopes, may be due
      in part to enhanced haptotaxis sustained by alpha3, alpha6, and beta1 integrin
      receptors, the activities of which are regulated by H or A/B glycosylation. These
      phenotypic changes provide a rationale for the deletion of A and B epitopes as
      one criterion defining human tumor malignancy.

PMID- 9242431
TI  - Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen
      activated protein kinase activation in human leukemia U937 cells.
AB  - In a previous study, we demonstrated that bufalin, which is an active principle
      of Chinese medicine, chan'su, caused apoptosis in human leukemia U937 cells by
      anomalous activation of mitogen-activated protein kinase (MAPK) via the signaling
      pathway of Ras, Raf-1, and MAPK kinase-1. Here, we report the effect of
      overexpression of bcl-2 in U937 cells on the signaling pathway of apoptosis that
      is induced by bufalin. The results indicated that the apoptosis induced by
      bufalin in U937 cells was significantly inhibited by overexpression of the Bcl-2
      protein. No significant difference was detected in the activation of MAPK kinase
      1 that is induced by bufalin in wild-type or Bcl-2-overexpressed U937 cells;
      however, the activation of MAPK by bufalin was significantly attenuated in the
      cells overexpressing Bcl-2. Bufalin treatment activated activator protein-1
      transcriptional activity; however, this activation was decreased to 40% in bcl-2
      overexpressed U937 cells. These results indicate that Bcl-2 acts downstream of
      MAPK kinase-1 but upstream of MAPK and suggest that, in the signaling pathway of
      the apoptotic process induced by bufalin, the transcriptional activity of
      activator protein-1 may be down-regulated through the inhibition of MAPK activity
      by Bcl-2.

PMID- 9242432
TI  - Inhibition of protein kinase C prevents asbestos-induced c-fos and c-jun proto
      oncogene expression in mesothelial cells.
AB  - Asbestos and the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13
      acetate (TPA), increase c-fos and c-jun mRNA levels and AP-1 DNA binding activity
      in rat pleural mesothelial (RPM) cells, a target cell of asbestos-induced
      mesotheliomas (N. H. Heintz et al., Proc. Natl. Acad. Sci. USA, 90: 3299-3303,
      1993). Because protein kinase C (PKC) is the intracellular receptor of phorbol
      ester tumor promoters and asbestos is a putative tumor promoter in the
      respiratory tract, we hypothesized that PKC might play a critical role in
      asbestos-induced cell signaling pathways associated with regulation of proto
      oncogenes. Using a panel of PKC antibodies, we identified PKC alpha as the major
      PKC isozyme in RPM cells. We then pretreated cells with phorbol ester dibutyrate
      to down-modulate PKC or with calphostin C, a specific PKC inhibitor, to determine
      if depletion of PKC alpha could block asbestos-induced c-fos/c-jun expression.
      Quantitation of Northern blots showed that fiber-associated c-fos/c-jun mRNA
      levels were significantly lower either after PKC alpha down-modulation or
      pretreatment with calphostin C. In addition, to determine whether tyrosine
      kinases also were involved in proto-oncogene activation by asbestos, tyrphostin
      AG82 or herbimycin A was added to RPM cells before exposure to asbestos. These
      inhibitors decreased crocidolite-induced c-fos but not c-jun levels, suggesting
      that tyrosine kinases have different regulatory roles in asbestos-induced c-fos
      versus c-jun signaling pathways. The ability to block induction of asbestos
      induced proto-oncogene expression using pharmacological intervention may be
      important in prevention and treatment of asbestos-induced proliferative diseases
      including lung cancers, mesothelioma, and pulmonary fibrosis.

PMID- 9242433
TI  - Comparative analysis of bone marrow and venous blood isolates from
      gastrointestinal cancer patients for the detection of disseminated tumor cells
      using reverse transcription PCR.
AB  - We investigated 141 bone marrow and 104 venous blood isolates from
      gastrointestinal cancer patients with a cytokeratin (CK) 20-specific nested
      reverse transcription PCR for the detection of disseminated tumor cells at time
      of primary tumor resection. In colorectal cancer patients, 20 of 65 (31%) bone
      marrow and 9 of 52 (17%) venous blood isolates yielded a CK 20 mRNA-positive
      result in a stage-dependent manner. The detection rates for gastric cancer
      patients were 11 of 49 (22%) and 5 of 30 (17%) for bone marrow and venous blood,
      respectively. In pancreatic cancer patients, positive signals were found in
      advanced tumor stage. A duplex PCR system improved the feasibility of the test.
      After analyzing 70 sets of bone marrow and venous blood isolates from colorectal,
      gastric, and pancreatic cancer patients, we observed a higher detection rate in
      bone marrow isolates. Survival of patients with CK 20 mRNA-positive findings was
      significantly shorter than that of negatively tested patients.

PMID- 9242434
TI  - Expression of pro form of prostate-specific antigen by mammalian cells and its
      conversion to mature, active form by human kallikrein 2.
AB  - To study the expression, biosynthesis, and processing of prostate-specific
      antigen (PSA) in mammalian cells, recombinant PSA was expressed in Syrian hamster
      tumor cell line AV12-664 (AV12-PSA). Expression of PSA was monitored by the
      Tandem-MP PSA assay. PSA was secreted into the medium during the logarithmic
      phase of cell growth at >9 microg/ml and was stable. The PSA purified from spent
      medium of AV12-PSA cells did not exhibit any enzymatic activity and did not
      complex with the protease inhibitor, alpha-1-antichymotrypsin. These findings
      indicated that an inactive form of PSA was expressed by AV12-PSA cells. NH2
      terminal sequencing confirmed the identity of the PSA purified from the spent
      medium of AV12-PSA cells to be pro-PSA. This demonstrates that PSA is expressed
      as pro-PSA by mammalian cells and suggests that pro-PSA may be present in
      biological fluids. Human kallikrein 2 (hK2), another member of the hK family, is
      also expressed predominantly in prostate epithelium. Although hK2 has been shown
      to exhibit trypsin-like activity, little is known about its natural substrates.
      Using purified proteins, we show that hK2 can convert pro-PSA to mature,
      enzymatically active PSA, thus establishing a physiological connection between
      hK2 and PSA. These findings imply that hK2 may be regulating PSA activity in
      vivo.

PMID- 9242435
TI  - Overexpression of Bcl-X(L) inhibits Ara-C-induced mitochondrial loss of
      cytochrome c and other perturbations that activate the molecular cascade of
      apoptosis.
AB  - High-dose Ara-C (HIDAC) induces the cleavage and activity of caspase-3
      (CPP32beta/Yama/apopain), resulting in the morphological and biochemical features
      of apoptosis. High levels of the antiapoptotic Bcl-x(L) or Bcl-2, relative to the
      proapoptotic Bax, have been shown to inhibit HIDAC-induced cleavage and activity
      of caspase-3 and apoptosis of the human acute myeloid leukemia HL-60 cells. In a
      previous report, we demonstrated this inhibition, using the control HL-60 (HL
      60/neo) cells and their counterparts, HL-60/Bcl-x(L), which have enforced
      overexpression of Bcl-x(L) and a significantly lower ratio of free to bound Bax.
      Results of the present studies demonstrate that, in the initiation phase of
      apoptosis of HL-60/neo cells due to HIDAC (10 or 100 microM for 4 h), cytochrome
      c is released from the mitochondria to the cytosol, followed by the loss of
      mitochondrial membrane potential (deltapsi m) and an increase in the reactive
      oxygen species; these events precede and trigger the cleavage and activity of
      caspase-3. These HIDAC-induced early mitochondrial and cytosolic perturbations,
      which represent the initiation phase of HIDAC-induced apoptosis, were inhibited
      in HL-60/Bcl-x(L) cells. HIDAC treatment for 4 h also modestly increased the
      intracellular levels of free Bax relative to Bax bound to Bcl-2 and Bcl-x(L) in
      HL-60/neo but not in HL-60/Bcl-x(L) cells. In HL-60/neo cells, HIDAC-induced
      progressive accumulation of cytochrome c in the cytosol, the decrease in deltapsi
      m, and the increase in reactive oxygen species were not inhibited by coculture
      with the tetrapeptide inhibitors of caspases that have been previously shown to
      inhibit Ara-C-induced cleavage and activity of caspase-3 and apoptosis. These
      findings indicate that Bcl-x(L) inhibits HIDAC-induced preapoptotic mitochondrial
      perturbations, which prevent the accumulation of cytochrome c in the cytosol,
      thereby preserving caspase-3 in the inactive zymogen state and checking the
      molecular cascade of apoptosis.

PMID- 9242436
TI  - Characterization of the rat and mouse homologues of the BRCA2 breast cancer
      susceptibility gene.
AB  - Inherited BRCA2 mutations confer profound susceptibility to human breast and
      ovarian cancer. The rat and mouse Brca2 homologues share 58% and 59% identity
      (72% similarity), respectively, with the human BRCA2 protein. The Brca2 proteins
      also share a potential nuclear localization signal (human codons 3263-3269) and a
      highly conserved large carboxyl region (77% identity, 86% similarity between
      human and rodents) that may represent important functional domains. At least six
      of eight previously described BRC repeats have been highly conserved in rats and
      mice. Expression studies demonstrate an 11-12 Kb transcript with rodent tissue
      specific patterns of expression consistent with human BRCA2. These results will
      facilitate studies of Brca2 function during normal and neoplastic development.

PMID- 9242437
TI  - Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic
      carcinomas.
AB  - The Rb/p16 tumor-suppressive pathway is abrogated frequently in human tumors,
      either through inactivation of the Rb or p16INK4a/CDKN2/MTS1 tumor-suppressor
      proteins, or through alteration or overexpression of the cyclin D1 or cyclin
      dependent kinase 4 oncoproteins. We reported previously that the p16 gene was
      genetically inactivated in 82% of pancreatic carcinomas. Nearly half of these
      inactivations were by intragenic mutation of p16, and the remainder were by
      homozygous deletion of the gene. Here, we analyzed pancreatic carcinomas for
      additional mechanisms by which the Rb/p16 pathway might be inactivated.
      Transcriptional silencing of the p16 gene in association with methylation of its
      5'-CpG island was examined by methylation-specific PCR in 18 pancreatic
      carcinomas. Nine of these were known to harbor an intragenic mutation in p16, and
      nine had a wild-type p16 coding sequence. Seven of the 18 tumors were
      hypermethylated, and all 7 were p16 wild-type (P = 0.001). Complete silencing of
      transcription from methylated wild-type gene sequences was demonstrated.
      Immunohistochemical analysis revealed normal expression levels of the Rb protein
      in all carcinomas studied. None of the carcinomas had genomic amplification of
      the cyclin D1 or CDK4 genes, and none had mutation of the p16-binding domain of
      CDK4. An additional p16 mutation was identified. In total, the Rb/p16 pathway was
      abrogated in 49 of the 50 carcinomas (98%) studied, all through inactivation of
      the p16 gene. Similar results were obtained in an independently analyzed series
      of 19 pancreatic carcinomas. These data demonstrate the central role of the
      Rb/p16 pathway in the development of pancreatic carcinoma.

PMID- 9242438
TI  - Aberrant splicing but not mutations of TSG101 in human breast cancer.
AB  - The 11p15 gene TSG101 was recently reported to undergo frequent large intragenic
      deletions in human breast cancer. Here we show that that is generally not the
      case, but the gene shows aberrant splicing, based on the following observations:
      identical products were observed in matching normal and fetal tissues; deleted
      cDNA sequence revealed canonical splicing donor and acceptor site sequences; and
      genomic Southern blots showed no intragenic deletions in all 72 tumors studied.
      Nevertheless, relaxation of RNA splicing fidelity may be an oncodevelopmental
      marker in cancer and may play a general role in other genes and tumors.

PMID- 9242439
TI  - Characterization of a high copy number amplification at 6q24 in pancreatic cancer
      identifies c-myb as a candidate oncogene.
AB  - In a recent study designed to identify chromosomal aberrations in pancreatic
      cancer tissues using comparative genomic hybridization, a high copy number
      amplification on 6q was detected. To identify the most likely candidate oncogene,
      the extension of the amplification in pancreatic cancer tissues and cell lines
      was determined by Southern blot analysis. Exon trapping was performed with DNA
      from a yeast artificial chromosome clone containing the complete minimally
      amplified region. Only fragments from two genes, namely, the c-myb oncogene and a
      novel gene, were shown to be amplified. The c-myb proto-oncogene was amplified in
      10% of the pancreatic carcinoma tissues and in the pancreatic cancer cell line
      PC2. Interestingly, the c-myb oncogene was overexpressed not only in the
      amplified samples but also in the majority of the examined pancreatic cancer
      tissues and cell lines, suggesting that amplification is only one of the
      mechanisms leading to overexpression. In contrast, the novel gene, which was
      called human eRF3b (eukaryotic release factor 3b), seems to be only coamplified
      with c-myb. Genetic alterations of c-myb were mainly found in advanced tumors,
      indicating a possible correlation to tumor progression and aggressive tumor
      phenotypes.

PMID- 9242440
TI  - Rapid analysis of distinctive CD44 RNA splicing preferences that characterize
      colonic tumors.
AB  - In normal tissues, the steady-state level of CD44 mRNA is low, and the variety of
      alternatively spliced transcripts produced by this complex gene is limited.
      Conversely, increased and disorderly expression of this gene has been observed in
      a number of types of cancer. This study analyzed the order in which the CD44
      variant exons are spliced together in gastrointestinal tumor cell lines and in 20
      colonic carcinomas and matched normal mucosa. We used a PCR-based assay to
      analyze specific exon junctions at the boundary of the standard and variant
      regions of the CD44 gene transcripts. This revealed characteristically different
      splicing preferences in colonic tumor and normal tissues. The junction of exon 5
      to exon 8 appeared to be the most prevalent in normal mucosa, whereas the
      presence of junctions between exon 5 and either exon 7, 9, or 11 were increased
      markedly in tumor samples. These observations demonstrate that the unusual
      variety of CD44 transcripts in cancer cells results from the fidelity of
      alternative splicing mechanisms being compromised and are potentially useful as
      tumor cell markers in diagnostic assays.

PMID- 9242441
TI  - Retinoblastoma binding factor 1 site in the core promoter region of the human RB
      gene is activated by hGABP/E4TF1.
AB  - We previously reported two oncogenic point mutations present in the RB
      (retinoblastoma) gene promoter region, found at consensus Sp1 and ATF sites,
      respectively, and in two separate hereditary RB families. However, Sp1 protein
      was shown not to bind to the Sp1 site; this indicated that the Sp1 consensus site
      mutation was blocking the action of an alternative transcription factor, which we
      called RBF-1 (retinoblastoma binding factor 1). Subsequent purification of RBF-1
      revealed it to be hGABP/E4TF1, a transactivator from the adenovirus early-region
      4 promoter. In this study, we directly examined the effects of hGABP/E4TF1 on
      transactivation of the RB gene promoter through the RBF-1 site. As expected,
      hGABP/E4TF1 enhanced the core RB promoter activity, whereas it did not stimulate
      a mutant RBF-1 site. We therefore conclude that the most essential transcription
      factor in the human RB gene is likely to be hGABP/E4TF1.

PMID- 9242442
TI  - Melanoma-inhibiting activity, a novel serum marker for progression of malignant
      melanoma.
AB  - Melanoma-inhibiting activity (MIA) was isolated previously as a small soluble
      protein secreted from malignant melanoma cell lines in vitro. In vivo, highly
      restricted expression patterns in melanocytic tumors were identified. We
      therefore quantitated serum levels of MIA protein by means of a nonradioactive
      ELISA and investigated whether MIA provides a clinically useful parameter in
      patients with malignant melanomas. Here, we report enhanced MIA serum levels in
      13 and 23% of patients with stage I and II disease, respectively, and in 100%
      with stage III or IV disease. Compared with S-100 and soluble intercellular
      adhesion molecule 1 serum levels in these patients, MIA was the most sensitive
      marker. Response to therapy in stage IV disease correlated with changes in MIA
      serum levels. Measuring repeatedly sera of 350 patients with a history of stage I
      or II melanoma during follow-up, we detected 32 patients developing positive MIA
      values. At the time of serum analysis, 15 of them had developed metastases, and
      one presented with metastatic disease 6 months later. In contrast, none of the
      patients with normal MIA serum levels developed metastases during the follow-up
      period of 6-12 months. In conclusion, MIA represents a novel serum marker for
      systemic malignant melanoma revealing the highest sensitivity and specificity
      among currently available markers. Useful clinical applications include staging
      of primary melanomas, detection of progression from localized to metastatic
      disease during follow-up, and monitoring therapy of advanced melanomas.

PMID- 9242444
TI  - Phorbol ester-induced cell surface association of matrix metalloproteinase-9 in
      human MCF10A breast epithelial cells.
AB  - Cell surface association of extracellular matrix (ECM)-degrading enzymes has been
      suggested to facilitate proteolysis of ECM in areas of cell-matrix contacts and
      to be crucial for the process of tumor cell invasion. Matrix metalloproteinase-9
      (MMP-9) is a member of the MMP family of endopeptidases that has been shown to
      play a critical role in hydrolysis of ECM components and has been localized on
      the surface of tumor cells. However, the nature of the cell surface association
      of MMP-9 is unknown. Here, we report the cell surface association of MMP-9 in
      human breast epithelial MCF10A cells treated with 12-O-tetradecanoylphorbol-13
      acetate (TPA). Surface biotinylation and immunoprecipitation with anti-MMP-9
      antibodies revealed the presence of two MMP-9 forms (M(r) 92,000 and 85,000) on
      the surface of TPA-treated MCF10A cells, whereas in the media, only the M(r)
      92,000 form was detected, mostly in complex with TIMP-1, a specific MMP-9
      inhibitor. The MMP-9 forms were also found in purified plasma membranes of TPA
      treated cells. In contrast, the plasma membranes contained little or no TIMP-1.
      The surface-bound MMP-9 forms were recognized by an antibody to the NH2-terminal
      prodomain, indicating that both represent latent enzymes. Pulse-chase analysis
      and endoglycosidase H digestion of surface-biotinylated MMP-9 forms demonstrated
      that the M(r) 85,000 species was endoglycosidase H sensitive, suggesting
      targeting of the precursor form of MMP-9 to the cell surface. These studies
      demonstrate a specific cell surface association of MMP-9 in response to TPA that
      may help to localize TIMP-1-free enzyme on the surface of breast epithelial
      cells.

PMID- 9242443
TI  - Deletions of chromosome 3p are frequent and early events in the pathogenesis of
      uterine cervical carcinoma.
AB  - To study the molecular abnormalities involved in the multistage development of
      cervical carcinoma (CC), we investigated the presence of oncogenic human
      papillomavirus (HPV) sequences, loss of heterozygosity (LOH), and microsatellite
      alterations at several genes/loci at 3p (3p14.2 at the FHIT gene, 3p14.3-21.1,
      3p21, and 3p22-24.2), 9p21, RB and P53, and P53 gene point mutations in precisely
      microdissected archival tissues from 20 CCs and their accompanying precursor
      lesions (cervical intraepithelial neoplasia, CIN; n = 40) and normal epithelia (n
      = 20). In all HPV-positive cases (90% of CCs), HPV sequences were detected as the
      earliest appearing molecular change or simultaneously with other changes. LOH at
      any 3p region was found in 70% of CCs, and 3p14.2 (FHIT gene/FRA3B fragile site)
      (56%) and 3p21 (57%) were the most frequent 3p sites of loss. LOH at some 3p
      region was in the CIN I stage, and the 3p deletions in precursor CIN lesions were
      smaller than the 3p losses found in the associated invasive CC. LOH at the other
      regions studied and P53 gene mutations were less frequent and later events.
      Microsatellite alterations were detected in 35% of CCs, and identical
      abnormalities were detected in the associated precursor lesions. Although
      infection with oncogenic HPV strains is the earliest and most frequent molecular
      event, progressive deletions at one or more 3p regions (particularly at 3p14.2,
      and 3p21) are also frequent events occurring early in the pathogenesis of CC.

PMID- 9242445
TI  - Src tyrosine kinase mediates stimulation of Raf-1 and mitogen-activated protein
      kinase by the tumor promoter thapsigargin.
AB  - Thapsigargin is a non-phorbol ester-type tumor promoter that elevates the
      intracellular Ca2+ (Ca(i)2+) levels by blocking the microsomal Ca2+ ATPase. At
      present, the consequence of this Ca(i)2+ increase and the nature of the
      tumorigenicity of thapsigargin still remain to be elucidated. Previously, we
      demonstrated that thapsigargin activates the mitogen-activated protein (MAP)
      kinase via Ca(i)2+ but independently of protein kinase C or Ca2+ influx. Here, we
      show that thapsigargin also rapidly stimulates the Src tyrosine kinase.
      Transfection of a v-Src gene into a hippocampal cell line (H19-7) renders a
      constitutive activation of MAP kinase, whereas transfection of a kinase-deficient
      Src mutant blocks the activation by thapsigargin, suggesting that Src is required
      for the thapsigargin-induced MAP kinase activation. Cotransfection of a dominant
      inhibitory Raf-1 and the v-Src genes into H19-7 cells results in an inhibition of
      the otherwise constitutively elevated MAP kinase activity, suggesting that Raf-1
      is required for the Src-dependent activation of MAP kinase. Similarly, in the LA
      90 cells, expression of a temperature-sensitive allele of v-Src constitutively
      activates Raf-1 and MAP kinase, whereas expression of a dominant-inhibitory Raf-1
      mutant abolishes the MAP kinase activation induced by either v-Src or
      thapsigargin treatment. Together, these results suggest that thapsigargin
      stimulates MAP kinase signaling via Src and Raf-1. The activation of this Src-MAP
      kinase pathway suggests a biochemical mechanism for the tumorigenic nature of
      thapsigargin.

PMID- 9242446
TI  - Cell cycle response to DNA damage differs in bronchial epithelial cells and lung
      fibroblasts.
AB  - Epithelial cells along the conducting airways can be more or less continuously
      exposed to DNA-damaging agents, which should limit their proliferation by
      inducing cell cycle checkpoints. Yet, paradoxically, airway epithelial cells
      frequently show a hyperplastic response when exposed to such agents. In this in
      vitro study, we assessed the hypothesis that normal human bronchial epithelial
      cells (BECs) are more resistant to the cell cycle-arresting effects of DNA damage
      than are human lung fibroblasts (HLFs), a cell type often investigated in the
      context of cell cycle checkpoints. Using ionizing radiation as a DNA-damaging
      insult, we have found that BECs indeed show less pronounced G1 and G2 delays than
      do fibroblasts. Unlike the HLFs, which ultimately enter a condition of apparently
      terminal arrest in the G1 phase of the cell cycle, BECs continue proliferating
      following their initial, transient G1 and G2 delays. Radiation-induced p53 and
      p21Cip1 increases were greater in HLFs than in BECs, whereas preexposure, basal
      levels of p53 were higher in BECs than in HLFs. The results of this investigation
      indicate that BECs may be less susceptible to the cell cycle-arresting effects of
      DNA-damaging agents, perhaps because of their higher basal levels of p53.
      Extension of these findings to the in vivo condition provides a possible
      explanation for airway epithelial cell hyperplastic responses that occur in a
      background of DNA-damaging stresses. Moreover, the attenuated DNA damage-induced,
      cell cycle checkpoint responses in BECs potentially may favor the transmission of
      DNA lesions to cell progeny.

PMID- 9242447
TI  - Targeted disruption of the epidermal growth factor receptor impairs growth of
      squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro
      keratinocyte responses to oncogenic ras.
AB  - We have assessed the role of epidermal growth factor receptor (EGFR) signaling in
      biological responses to the v-ras(Ha) oncogene using primary keratinocytes from
      Egfr -/- mice and wild-type littermates. On the basis of several criteria, Egfr 
      /- keratinocytes were unresponsive to either acute or chronic exposure to several
      EGFR ligands but were stimulated to proliferate in response to several other
      mitogens. Although conditioned medium from primary keratinocytes transduced with
      v-ras(Ha) retrovirus (v-ras(Ha) keratinocytes) was a potent mitogen for wild-type
      but not Egfr -/- keratinocytes, v-ras(Ha) transduction of primary keratinocytes
      of either genotype resulted in a strong mitogenic response, arguing against an
      obligatory role for EGFR activation in v-ras(Ha)-mediated stimulation of
      keratinocyte proliferation. Infection with high-titer v-ras(Ha) retrovirus
      altered the keratin expression pattern in keratinocytes of both genotypes,
      suppressing differentiation-specific keratins K1 and K10 while activating
      aberrant expression of K8 and K18. In wild-type but not Egfr -/- cultures, K1 and
      K10 were also suppressed following infection at lower retroviral titers,
      presumably as a result of paracrine EGFR activation on uninfected cells present
      in these cultures. Squamous papillomas produced by grafting Egfr -/- v-ras(Ha)
      keratinocytes onto nude mice were only 21% of the size of wild-type v-ras(Ha)
      tumors, and a striking redistribution of S-phase cells was detected by
      immunostaining for bromodeoxyuridine. In Egfr -/- v-ras(Ha) papillomas, the
      fraction of total labeled nuclei detected in suprabasal layers was increased from
      19 to 39%. In contrast, the basal layer labeling index of Egfr -/- papillomas was
      reduced to 34%, compared to 43% in wild-type tumors. Our results indicate that,
      although autocrine EGFR signaling is not required for keratinocyte responses to
      oncogenic ras in culture or benign tumor formation in nude mouse grafts,
      disruption of this pathway impairs growth of v-ras(Ha) papillomas by a mechanism
      that may involve alterations in keratinocyte cell cycle progression and/or
      migration in vivo.

PMID- 9242448
TI  - Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation
      with patient survival.
AB  - E-cadherin maintains the normal differentiated phenotype in epithelial cells;
      this function is partly mediated by alpha-catenin, which links E-cadherin to the
      cell cytoskeleton. Dysfunction of E-cadherin in vitro and in vivo is associated
      with an invasive phenotype. However, the role of alpha-catenin is largely
      undetermined. We analyzed the expression of E-cadherin and alpha-catenin in
      prostate cancer to assess the relationship of abnormal expression to stage, grade
      and survival. E-cadherin expression was evaluated in 99 prostate cancers. In 79
      of those specimens, alpha-catenin was also assessed. In benign prostatic
      epithelium, both E-cadherin and alpha-catenin were expressed uniformly at the
      cell membrane. Abnormal E-cadherin expression was found in 56% of cancer
      specimens, whereas alpha-catenin expression was abnormal in 42%. Abnormal
      expression of each molecule was significantly correlated with Gleason score (P <
      0.0001) and the ratio of resection chippings infiltrated by tumor (P < 0.0001). E
      cadherin expression was also associated with the extent of disease on the initial
      bone scan (P = 0.017). Univariate analysis showed significantly lower survival
      rate for patients with abnormal E-cadherin (P = 0.0003) or alpha-catenin
      expression (P = 0.031). Multivariate regression analysis showed that the
      prognostic value of E-cadherin was independent of tumor grade but not of
      metastasis. These results suggest that perturbation of cell-cell adhesion is
      involved in the progression of prostate cancer and that analysis of E-cadherin
      expression may be clinically useful.

PMID- 9242449
TI  - Tumor necrosis factor enhances parathyroid hormone-related protein-induced
      hypercalcemia and bone resorption without inhibiting bone formation in vivo.
AB  - Humoral hypercalcemia of malignancy results from the effects of tumor-produced
      factors on bone, kidney, and intestine that disrupt normal calcium homeostasis.
      Although parathyroid hormone-related protein (PTHrP) is a major mediator of the
      syndrome, tumors also produce other hypercalcemic factors, such as tumor necrosis
      factor (TNF), which may modulate the effects of PTHrP. It has been postulated
      that TNF may counteract the stimulatory effects of PTHrP on bone formation. To
      examine the effects of TNF on PTHrP-induced changes in calcium and bone
      metabolism, a murine tumor model of hypercalcemia was used. Nude mice were
      inoculated with Chinese hamster ovarian (CHO) cells expressing human TNF
      (CHO/TNF) or nontransfected CHO cells (CHO/-) and further treated with injections
      of human PTHrP(1-34) or vehicle. The effects of TNF, PTHrP, and the combination
      of the two factors on blood ionized calcium, osteoclast recruitment, and bone
      histomorphometry were evaluated. Mice bearing CHO/TNF tumors that were injected
      with PTHrP had significantly higher calcium concentrations, increased committed
      osteoclast progenitors, and mature osteoclasts as well as enhanced bone
      resorption compared with mice bearing CHO/TNF tumors injected with vehicle or
      those bearing CHO/- tumors injected with PTHrP or vehicle. A 2-fold increase in
      new woven bone formed in the calvaria at sites of previous bone resorption was
      observed in CHO/TNF mice treated with PTHrP. Bone formation rates in the
      vertebrae were similar in both CHO/- and CHO/TNF mice treated with PTHrP. These
      data demonstrate that the hypercalcemic effects of PTHrP are enhanced by TNF and
      that this effect is due to the increased production of committed osteoclast
      precursors with a subsequent increase in osteoclastic bone resorption.
      Furthermore, PTHrP caused a coupled increase in osteoclastic bone resorption and
      new bone formation that was not inhibited by TNF. These findings highlight the
      complex interactions that may occur between tumor-produced factors on bone that
      result in malignancy-associated hypercalcemia and suggest that TNF may not be
      responsible for the decreased bone formation seen in some patients with this
      condition.

PMID- 9242450
TI  - Antisense oligonucleotides specific for transforming growth factor beta2 inhibit
      the growth of malignant mesothelioma both in vitro and in vivo.
AB  - Transforming growth factor beta (TGF-beta) is a potent growth-regulatory and
      immunomodulatory cytokine that exerts a diverse range of effects on many types of
      cells. High levels of TGF-beta are produced by several human and mouse malignant
      mesothelioma (MM) cell lines, and it is known to act as a growth factor for these
      cells. Antisense oligonucleotides (ODNs), targeted against specific TGF-beta
      mRNA, were used to block TGF-beta production from MM cells in vitro and in vivo.
      TGF-beta antisense ODNs were encapsulated in liposomes and transfected into MM
      cells or delivered intratumorally. TGF-beta2 mRNA levels, assessed by
      semiquantitative PCR, and TGF-beta2 protein secretion were reduced after TGF
      beta2 antisense ODN transfection. MM cell proliferation, assessed by tritiated
      thymidine uptake, was specifically inhibited by both TGF-beta1- and TGF-beta2
      specific antisense ODNs. In vivo administration of TGF-beta2 antisense ODNs,
      delivered locally, reduced tumor growth. These data show that the blockade of TGF
      beta2 within this tumor reduces tumor growth and raises the possibility that TGF
      beta2 antisense ODNs may be useful as a therapy for this disease.

PMID- 9242451
TI  - Mechanism of action of E7010, an orally active sulfonamide antitumor agent:
      inhibition of mitosis by binding to the colchicine site of tubulin.
AB  - E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonami de),
      an orally active sulfonamide antitumor agent that is currently in a Phase I
      clinical trial, showed rather consistent growth-inhibitory activities against a
      panel of 26 human tumor cell lines (IC50 = 0.06-0.8 microg/ml), in contrast to
      vincristine (VCR; IC50 = 0.0002-0.04 microg/ml), 5-fluorouracil (IC50 = 0.2-30
      microg/ml), Adriamycin (IC50 = 0.002-0.7 microg/ml), mitomycin C (IC50 = 0.007-3
      microg/ml), 1-beta-D-arabinofuranoxylcytosine (IC50 = 0.005 to >30 microg/ml),
      camptothecin (IC50 = 0.002-0.4 microg/ml), and cisplatin (IC50 = 0.5-20
      microg/ml). It caused a dose-dependent increase in the percentage of mitotic
      cells in parallel with a decrease in cell proliferation, like VCR. It also showed
      a dose-dependent inhibition of tubulin polymerization, which correlated well with
      the cell growth-inhibitory activity. 14C-labeled E7010 bound to purified tubulin,
      and this binding was inhibited by colchicine but not by VCR. However, its binding
      properties were different from those of colchicine, as well as those of VCR.
      E7010 was active against two kinds of VCR-resistant P388 cell lines, one of which
      showed multidrug resistance due to the overexpression of P-glycoprotein
      (resistant to Taxol), and the other did not show multidrug resistance (sensitive
      to Taxol). Furthermore, four E7010-resistant P388 cell lines showed no cross
      resistance to VCR, a different pattern of resistance to podophyllotoxin, and
      collateral sensitivity to Taxol. Therefore, E7010 is a novel tubulin-binding
      agent that has a wider antitumor spectrum than VCR and has different properties
      from those of VCR or Taxol.

PMID- 9242452
TI  - T-cell recognition of tumor-associated carbohydrates: the nature of the glycan
      moiety plays a decisive role in determining glycopeptide immunogenicity.
AB  - Aberrant glycosylation is one of the most constant traits of the malignant cell
      phenotype. To study T-cell responses to tumor-associated glycans, the mouse
      hemoglobin-derived decapeptide Hb(67-76), which binds well to the MHC class II
      molecule E(k) and is nonimmunogenic in CBA/J mice, was either O- or N
      glycosylated at its primary T-cell receptor contact residue, position 72, with
      different glycans attached to either threonine, serine, or asparagine. The
      carbohydrate moieties included tumor-associated mucins, i.e., the Tn and T
      antigens, mucin-related glycans, and mucin-unrelated glycans. The side chain of
      the amino acid in position 72 points away from the MHC binding site when the
      Hb(67-76) peptide is bound to E(k), so the assumption was that this was also the
      case for glycans attached to this position. The glycosylated Hb(67-76) peptide
      analogues were then studied for binding to E(k) and for immunogenicity in CBA/J
      mice. All 16 glycopeptides bound well to E(k), although those with the more
      complex carbohydrates bound more weakly than those with monosaccharides. Six of
      12 O-glycosylated and 0 of 4 N-glycosylated glycopeptides were able to induce a T
      cell proliferative response with a stimulation index above 3.0. Some
      glycopeptides were not immunogenic, suggesting that there may be holes in the T
      cell repertoire due to a lack of T-cell receptor regions accommodating certain
      glycan structures. The four strongest immunogenic glycopeptides were all O
      glycosylated, and interestingly, three of them carried the tumor-associated Tn or
      T antigen. On the other hand, the Hb(67-76) peptide analogue with the natural
      mucin Core2 structure attached did not elicit any T-cell response. T cells primed
      to a glycopeptide with a simple glycan structure such as Tn did not cross-respond
      significantly to other glycopeptides, indicating a high degree of carbohydrate
      specificity in T-cell recognition. T cells primed to a glycopeptide carrying the
      more complex T antigen showed a complicated pattern of cross-responses to
      glycopeptides with simpler glycan moieties. The fact that it is possible to raise
      MHC class II-restricted T-cell responses against tumor-associated carbohydrate
      structures opens new perspectives for the designing of cancer vaccines.

PMID- 9242453
TI  - Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and
      tyrosinase in human melanoma cell lines and in human melanocytic lesions.
AB  - In recent years, it has become evident that T cells can recognize peptides of
      melanocytic lineage antigens such as gp100, MART-1, and tyrosinase at the tumor
      cell surface and can subsequently destroy these cells. It is thus feasible to
      develop immunotherapeutic approaches based on the melanocytic marker profiles of
      melanoma cells. One of the predictors of the success rate of such a treatment is
      the extent of positive (target) tumor cells within the lesions of the patient.
      First, we investigated the presence of these three proteins in 18 human melanoma
      cell lines using RT-PCR and immunohistochemistry. In 11 cell lines, mRNA and
      protein of all three markers could be detected; in one cell line, only two
      markers were present, and six melanoma cell lines showed no evidence for these
      markers. Secondly, we stained frozen sections of 105 human melanocytic lesions,
      13 common nevocellular nevi, 13 atypical nevi, 13 early primary melanomas
      (Breslow < 1.5 mm), 25 advanced primary melanomas (aPM; Breslow > or =1.5 mm),
      and 41 melanoma metastases (MM) with antibodies against glycoprotein 100,
      melanoma antigen recognized by T cells, and tyrosinase. In addition, we used the
      3,4-dihydroxy-L-phenylalanine reaction to detect tyrosinase enzyme activity as a
      confirmation of the tyrosinase immunohistochemical results in a subset of the
      lesions. In the benign lesions, glycoprotein 100 was more prominently expressed
      in epidermal melanocytes, whereas melanoma antigen recognized by T cells was
      encountered in all or nearly all dermal melanocytes in all nevocellular nevi and
      atypical nevus lesions. Tyrosinase was found in a lower percentage of
      melanocytes, both in the epidermis and in the dermis within these lesions. With
      regard to heterogeneity of staining within the malignant lesions, we found that
      54% (early primary melanomas), 48% (aPMs), and 56% (MM) of the lesions stained
      within the same staining category for all three proteins studied. Approximately
      17% of the aPM and MM lesions did not show positive tumor cells for any of the
      three proteins. We conclude that a subgroup of patients with high expression
      should be selected for immunotherapeutic treatment approaches based on the
      presence of these proteins.

PMID- 9242454
TI  - Reduced efficacy of allogeneic versus syngeneic fibroblasts modified to secrete
      cytokines as a tumor vaccine adjuvant.
AB  - We examined the relative efficacy of allogeneic versus syngeneic fibroblasts
      admixed with tumor cells as a vaccine to induce antitumor T-cell reactivity.
      Allogeneic (3T3) or syngeneic (BLK) fibroblasts transfected to secrete equivalent
      amounts of GM-CSF were admixed with either D5 melanoma or MCA 207 sarcoma and
      inoculated s.c. into the flanks of C57BL/6 mice. Vaccine-primed lymph node (LN)
      cells were examined for in vivo antitumor reactivity in an adoptive transfer
      model. At fibroblast: tumor cell ratios of < or=1, allogeneic and syngeneic
      granulocyte macrophage colony-stimulating factor-secreting fibroblasts enhanced T
      cell reactivity to tumor cells. However, at ratios of 2.4, the adjuvant effect
      induced by granulocyte macrophage colony-stimulating factor was not evident.
      Instead, we observed increased alloreactivity of primed LN cells against 3T3
      targets as assessed by cytotoxicity and cytokine release assays, which was not
      observed with syngeneic fibroblasts. Moreover, with increasing numbers of
      allogeneic fibroblasts, there was a skewing of the T-cell Vbeta repertoire. These
      latter cells responded to tumor stimulation with the release of greater amounts
      of interleukin 10, which may account for the diminished antitumor reactivity
      observed in vivo. Allogeneic fibroblasts transduced to secrete interleukin 2 or
      IFN-gamma also induced diminished tumor reactivity of primed LN cells. Syngeneic
      fibroblasts are superior to allogeneic fibroblasts as vehicles to deliver
      cytokines in tumor vaccines.

PMID- 9242455
TI  - Isolation of novel HLA-DR restricted potential tumor-associated antigens from the
      melanoma cell line FM3.
AB  - Endogenous peptides bound to the constitutively expressed MHC class II molecules
      HLA-DR and HLA-DQ of the melanoma cell line FM3 were examined. By a combination
      of analytical methods (narrow bore and capillary reversed-phase high-performance
      liquid chromatography with subsequent spotting on polyvinylidene difluoride
      membranes, matrix-assisted laser desorption ionization mass spectrometry, and
      Edman microsequencing), we were able to isolate and identify a panel of HLA-DR4/2
      (HLA-DRB1*0401/0201/DRB5*0101)-associated self-peptides from the melanoma cell
      line FM3. Among ubiquitously HLA-DR-associated peptides such as peptides from the
      class II-associated invariant chain peptide region of the invariant chain, HLA
      class I, the transferrin receptor, and the IFN-gamma receptor, we identified
      several potential tumor-associated antigens stemming from the MHC class I
      restricted tumor antigen gp100, the Ca2(+)-binding protein annexin II, and
      proteins from the hsp70 family. Chinese hamster ovary cells cotransfected with
      HLA-DRA, DRB1*0401, and CD80 genes were shown specifically to prime T lymphocytes
      from HLA-DRB1*0401 donors to the annexin II and gp100 peptides. These results
      demonstrate that MHC class II molecules expressed by melanoma cells potentially
      present a variety of novel antigens to the immune system, some of which could be
      exploited for immunotherapy.

PMID- 9242456
TI  - Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39
      families.
AB  - We have previously reported on the analysis of TP53 coding mutations in 12
      classic Li-Fraumeni syndrome (LFS) families plus 9 families that were Li-Fraumeni
      like (LFL) families (J. M. Birch et al., Cancer Res., 54: 1298-1304, 1994).
      Mutations were found in 6 of 12 LFS families and in 1 of 9 LFL families. We have
      now extended these studies to include an additional nine LFS and nine LFL
      families, and TP53 mutations have been detected in eight of nine LFS families and
      in three of nine LFL families. Six of the new mutations described here are the
      same as those previously identified in other Li-Fraumeni families and are
      missense mutations at codons 245, 248, and 273 (in two families); a nonsense
      mutation at codon 209; and a mutation at the splice donor site in exon 4. The
      other five mutations are novel germ-line mutations and include missense mutations
      at codons 136 and 344, a 2-bp deletion within codon 191, a splice acceptor
      mutation in intron 3, and a 167-bp deletion of part of exon 1 and intron 1. In
      addition, we have detected a codon 175 mutation in a family previously reported
      as TP53 negative. To summarize all of the data from the families we have studied
      in this and our previous report (J. M. Birch et al., Cancer Res., 54: 1298-1304,
      1994), mutations have been detected in 15 of 21 LFS families (71%) and in 4 of 18
      LFL families (22%). These figures are somewhat higher than those previously
      reported by us and others for the frequency of TP53 mutations in LFS and LFL
      families. This could reflect our analysis of all 11 exons of TP53, including
      noncoding regions, as well as the use of direct sequencing rather than other less
      sensitive mutation detection methods.

PMID- 9242457
TI  - Differential induction of c-Jun NH2-terminal kinase and c-Abl kinase in DNA
      mismatch repair-proficient and -deficient cells exposed to cisplatin.
AB  - The c-Abl nonreceptor tyrosine kinase and the c-Jun NH2-terminal kinase
      (JNK/stress-activated protein kinase) are activated during the injury response to
      the DNA-damaging agent cisplatin. Loss of DNA mismatch repair activity results in
      resistance to cisplatin in human cancer cells, suggesting that the mismatch
      repair proteins function as a detector for cisplatin DNA adducts. To identify
      signaling pathways activated by this detector, we investigated the effect of the
      loss of DNA mismatch repair function on the ability of cisplatin to activate the
      JNK and c-Abl kinases. The results demonstrate that cisplatin activates JNK
      kinase 3.8 +/- 0.2-fold more efficiently in DNA mismatch repair-proficient than
      repair-deficient cells, and that activation of c-Abl is completely absent in the
      DNA mismatch repair-deficient cells. Furthermore, the results show that cisplatin
      induced activation of JNK occurs through a stress-activated protein
      kinase/extracellular signal-regulated kinase kinase 1-independent mechanism. We
      conclude that activation of JNK and c-Abl by cisplatin is in part dependent upon
      the integrity of DNA mismatch repair function, suggesting that these kinases are
      part of the signal transduction pathway activated when mismatch repair proteins
      recognize cisplatin adducts in DNA.

PMID- 9242458
TI  - The putative tumor suppressor BIN1 is a short-lived nuclear phosphoprotein, the
      localization of which is altered in malignant cells.
AB  - BIN1 is a putative tumor suppressor that was identified in a genetic screen for
      polypeptides that interact with the MYC oncoprotein. Using a set of six
      monoclonal antibodies, we identified and examined biochemical features and
      localization of cellular BIN1. Epitope mapping indicated that a putative nuclear
      localization motif and the MYC-binding domain were among the regions recognized
      by five antibodies. In immunoprecipitation and Western analyses, cellular BIN1
      was identified in human and rodent cells as a monomeric phosphoprotein of M(r)
      approximately 70,000. Pulse-chase experiments showed that BIN1 was short-lived,
      with a half-life of approximately 2 h. Cell immunofluorescence experiments
      revealed overlapping but unique nuclear localization patterns distinguished by
      two different antibodies. In normal cells, BIN1 was predominantly nucleoplasmic
      but was also present in a subnuclear compartment. Conversely, in a panel of tumor
      cells that expressed BIN1, the predominant localization was the subnuclear
      compartment. Taken together, the results suggested that the antibodies recognized
      different isoforms or conformations of BIN1, the localization of which varied
      between normal and tumor cells. This study will facilitate further analysis of
      the structure and regulation of BIN1 in normal and malignant cells.

PMID- 9242459
TI  - Protective effect of the insulin-like growth factor I receptor on apoptosis
      induced by okadaic acid.
AB  - Okadaic acid (OKA), a potent inhibitor of serine phosphatases at concentrations
      as low as 20-25 nM, induces apoptosis of R- mouse embryo fibroblasts, which are
      3T3-like cells devoid of type 1 insulin-like growth factor receptors (IGF-IRs).
      From R- cells, we have generated (by stable transfection) cell lines with IGF-IR
      numbers ranging from 0 (R- cells) to >10(6) receptors per cell. The wild-type IGF
      IR protects R- cells from OKA-induced apoptosis, its protective effect being
      exquisitely dependent on the number of receptors. A small increment in wild-type
      receptor number (from 15 x 10(3) to 22 x 10(3) receptors/cell) is sufficient to
      change R(-)-derived cells from sensitive to resistant to apoptosis. We have also
      studied the effect of various mutations of the IGF-IR on its ability to protect
      R(-)-derived cells from OKA-induced apoptosis. Our data indicate a correlation
      between protection from apoptosis and the ability of the receptor to respond to
      insulin-like growth factor I with mitogenesis.

PMID- 9242460
TI  - Prognostic significance of HER2 and HER4 coexpression in childhood
      medulloblastoma.
AB  - Recent in vitro studies of the epidermal growth factor receptor (EGFR) family
      have revealed complex signaling interactions involving the production of ligand
      mediated heterodimers synergistic for the transformation of cells in vitro. In a
      series of 70 patients with childhood medulloblastoma, we have used
      immunohistochemistry and Western blotting analysis to investigate the expression
      patterns of all four EGFR family members (EGFR, HER2, HER3, and HER4) and
      heregulin-alpha, a ligand for the HER3 and HER4 receptors. The majority of cases
      expressed two or more receptor proteins; coexpression of the HER2 and HER4
      receptors occurred in 54%. Expression of the ligand heregulin-alpha was detected
      in 31% of tumors. To investigate whether coexpression results in receptor
      heterodimerization, we have also performed immunoprecipitation analysis of
      protein extracts from primary tumors, and we demonstrate various patterns of
      receptor interaction including between HER2 and HER4. In multivariate 25-year
      survival analysis with clinicopathological disease features, no individual
      receptor or heregulin-alpha achieved significance. In contrast, when considered
      together in the multivariate model, coexpression of HER2 and HER4 demonstrated
      independent prognostic significance (P = 0.006). These data suggest the
      hypothesis that HER2-HER4 receptor heterodimerization is of particular biological
      significance in this disease, and this report is the first to demonstrate
      potential clinical significance of EGFR family heterodimerization in human
      cancer. Finally, we have also analyzed expression of the AP-2 transcription
      factor implicated in the positive regulation of HER2 and HER3 gene transcription
      in malignant cells and reveal an association between AP-2 expression and not only
      HER2 and HER3, but also HER4 levels in medulloblastoma primary tumors.

PMID- 9242461
TI  - Cloning of P2XM, a novel human P2X receptor gene regulated by p53.
AB  - Through cloning of functional p53-binding sites (p53-tagged sites) from the human
      genome, we isolated a novel gene inducible by wild-type p53. Its cDNA sequence
      contained an open reading frame encoding a 431-amino acid peptide that showed a
      significant homology with members of the P2X family. This protein also revealed a
      similarity to RP-2, a gene activated in thymocytes undergoing programmed cell
      death. Northern blot analysis showed that it was expressed predominantly in
      skeletal muscle. Hence, we designated the gene P2XM (P2X specifically expressed
      in skeletal muscle). P2XM was localized to chromosomal band 22q11, where frequent
      loss of heterozygosity has been observed in rhabdoid tumors. Although we detected
      no genetic alteration in the coding sequences, one of four rhabdomyosarcoma cell
      lines examined had completely lost expression of this gene. Furthermore, a minor
      splice variant lacking a part of exon 1 that would encode residues corresponding
      to transmembrane domain M1 was relatively more abundant in two of seven sarcoma
      cell lines, one of which was derived from a rhabdomyosarcoma, and the other was
      derived from an osteosarcoma. The results suggest that P2XM may play a
      significant role in the proliferation and/or differentiation of skeletal muscle
      cells and that its altered expression may be involved in the development of some
      sarcomas.

PMID- 9242462
TI  - Inhibition of nonsense-mediated messenger RNA decay in clinical samples
      facilitates detection of human MSH2 mutations with an in vivo fusion protein
      assay and conventional techniques.
AB  - Germ-line mutations in the human MSH2 (hMSH2) gene account for about 40% of known
      defects in kindreds with hereditary nonpolyposis colon cancer. We describe a
      simple fusion protein assay for detection of hMSH2 nonsense mutations in yeast.
      Detection of nonsense mutations with this assay is severely compromised in many
      cases by nonsense-mediated mRNA decay, a physiological process that destabilizes
      the mutant RNA. Triggering of nonsense-mediated decay requires mRNA scanning by
      the ribosome to detect the stop codon. We show that treatment of cells with the
      translation inhibitor puromycin suppresses nonsense-mediated decay and
      facilitates the detection of nonsense mutations in clinical samples by cDNA
      sequencing, in vitro protein truncation tests, and the yeast fusion protein
      assay. Given the prevalence of chain-terminating mutations in human disease
      genes, puromycin treatment of blood samples should improve the signal-to-noise
      ratio and hence the sensitivity of many RNA-based diagnostic tests.
      Paradoxically, the yeast hMSH2::ADE2 fusion protein assay also detects some in
      frame mutations, presumably through an effect on the folding of the fusion
      protein.

PMID- 9242463
TI  - Restriction landmark genomic scanning (RLGS-M)-based genome-wide scanning of
      mouse liver tumors for alterations in DNA methylation status.
AB  - Restriction landmark genomic scanning for methylation (RLGS-M) was used to
      detect, and subsequently clone, genomic regions with alterations in DNA
      methylation associated with tumorigenesis. Use of a methylation-sensitive enzyme
      for the landmark cleavage allows analysis of changes in methylation patterns. In
      this study, we used RLGS-M to analyze SV40 T antigen-induced mouse liver tumors
      derived from interspecific F1 hybrids between Mus spretus (S) and C57BL/6 (B6).
      Because 575 S- and B6-specific RLGS loci/spots have been mapped, tumor-related
      alterations in the RLGS profile could be immediately localized to specific
      chromosomal regions. We previously found that the loss of contiguous loci/spots
      could be attributed primarily to DNA loss, whereas loss of solitary loci/spots
      could be attributed primarily to DNA methylation. In this study, we examined 30
      mouse liver tumor samples for loss of the 507 mapped loci/spots. Fourteen
      solitary loci/spots found to be absent or reduced in more than 75% of tumor
      samples were cloned and subjected to DNA sequence analyses. Two loci were
      identified as alpha4 integrin and p16/CDKN2, genes reported to be involved in
      tumorigenesis. Thus, RLGS-M can detect alterations in the methylation status of
      known tumor suppressor genes and provide a method for detecting and subsequently
      cloning novel genomic regions that undergo alterations in methylation during
      tumorigenesis.

PMID- 9242464
TI  - Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in
      vivo: studies with 1400W, a novel inhibitor.
AB  - We have investigated the effect of N-(3-(aminomethyl)benzyl)acetamidine (1400W),
      a novel and highly selective inhibitor for inducible NOS (iNOS), on in vivo
      growth of solid tumors expressing iNOS. For the EMT6 murine mammary
      adenocarcinoma, in which iNOS is expressed in the tumor cells, continuous
      infusion of 1400W for 6 days at 10 or 12 mg/kg(-1)/h(-1) resulted in significant
      reduction in tumor weight (357 +/- 46 and 466 +/- 70 mg, respectively) compared
      with that of controls [726 +/- 65 (P < 0.001) and 796 +/- 88 mg (P < 0.02),
      respectively]. Reduced growth was also observed for a human tumor xenograft
      (colon adenocarcinoma DLD-1) genetically engineered to express iNOS
      constitutively and treated for 13 days with 6 mg/kg(-1)/h(-1) 1400W compared with
      controls (tumor weights 340 +/- 50 and 580 +/- 90 mg, respectively; P < 0.03).
      Growth of the parental DLD-1 clone was not altered with this treatment compared
      with that of controls (tumor weights 170 +/- 10 and 240 +/- 50 mg, respectively).
      Inhibition of iNOS in vivo was confirmed by decreases in plasma nitrite + nitrate
      concentrations in treated animals compared with that of controls (63-83%
      decreases for all experiments) and was supported by plasma and tumor
      concentrations of 1400W that were equivalent and 2.6-4.9 times higher than the
      EC50 previously reported for iNOS in a tissue assay. For the murine colon
      adenocarcinoma Colon 38, in which intratumoral macrophages are the predominant
      source of iNOS and which had high intratumoral arginine concentrations, 1400W
      treatment had no effect on growth or plasma nitrate + nitrate. Future studies
      with more potent selective iNOS inhibitors and a wider range of tumors may
      determine whether iNOS inhibitors could represent a novel approach to the
      treatment of cancer. These studies confirm that nitric oxide production in tumors
      plays a role in promoting their growth, rather than a role as a host defense
      mechanism in inhibiting growth.

PMID- 9242465
TI  - Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors
      affects invasive growth of tumor cells: in vitro analysis of tumor-stromal
      interactions.
AB  - Invasive and metastatic potentials of several types of carcinoma cells are
      regulated through interactions with host stromal cells, e.g., tumor-stromal
      interactions. Because hepatocyte growth factor (HGF), a ligand for the c-Met
      proto-oncogene product, is a mesenchymal- or stromal-derived factor that induces
      mitogenic, motogenic, and morphogenic responses, we examined the mechanisms
      involved in tumor-stromal interactions in vitro. The c-Met/HGF receptor was
      expressed in A431 human epidermoid carcinoma cells, A549 human non-small cell
      lung cancer cells, HuCC-T1 human cholangiocellular carcinoma cells, and SBC-3
      human small cell lung carcinoma cells. HGF stimulated cell growth, scattering,
      and invasion of these cells. Although these cells did not produce biologically
      significant levels of HGF, these cells did secrete soluble factors that potently
      stimulated HGF production in human skin fibroblasts. These carcinoma cell-derived
      HGF inducers proved to be interleukin-1 (IL-1) in A431 cells, IL-1 plus basic
      fibroblast growth factor (bFGF) in A549 and HuCC-T1 cells, and bFGF plus platelet
      derived growth factor in SBC-3 cells. When these carcinoma cells were cocultured
      with fibroblasts, HGF levels in the coculture system were much higher than the
      levels in fibroblasts alone, without cocultured carcinoma cells. Together with
      the increase in HGF levels, the number of invasive cells increased, but in vitro
      invasion of carcinoma cells in the coculture system was strongly inhibited by
      anti-HGF antibodies. Thus, there are mutual interactions between carcinoma cells
      and fibroblasts: IL-1, bFGF, and platelet-derived growth factor derived from
      tumor cells play a role in inducing HGF expression in stromal fibroblasts,
      whereas fibroblast-derived HGF, in turn, leads to invasive growth in carcinoma
      cells. The mutual interactions, as mediated by HGF and HGF inducers, may play a
      significant role in the occurrence of invasion and metastasis of carcinoma cells.

PMID- 9242466
TI  - Preclinical evaluation of the fluorinated 2-nitroimidazole N-(2-hydroxy-3,3,3
      trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR-4554) as a probe for the
      measurement of tumor hypoxia.
AB  - A novel probe, N-(2-hydroxy-3,3,3,-trifluoropropyl)-2-(2-nitro-1-imidazolyl)
      acetamide (SR-4554), has been used to detect tumor hypoxia noninvasively by 19F
      magnetic resonance spectroscopy (19F MRS). The compound was designed to undergo a
      hypoxia-dependent, one-electron reduction to metabolites that are selectively
      retained in tumors and has attractive pharmacokinetic, toxicological, and
      detection sensitivity properties. As a prelude to clinical studies, we report
      here for the first time on the ability to detect a MR signal following SR-4554
      administration in various transplantable tumors and describe validation studies,
      consisting of a correlation between signal retention and radiobiological hypoxic
      fraction, and the effects of modulating the degree of hypoxia by hydralazine and
      carbogen breathing. SR-4554 was absorbed and then eliminated from EMT6 tumors
      with a half-life of 51 min following an injection of 180 mg/kg i.p. of SR-4554.
      Using a quantitative 19F MRS technique, the 19F retention index (19FRI; 19F
      signal level at 6 h/45 min) was determined for four commonly used murine tumors
      (EMT6, SCCVII, KHT, and RIF-1). The retention of high tumor concentrations of
      fluorinated probe at 6 h, despite the much lower (20-fold) concentration of
      parent SR-4554 detected by high-performance liquid chromatography, was consistent
      with the involvement of one or more nitroreduced metabolites and suggested that
      19F MRS might give a quantitative measure of tumor hypoxia. In these murine
      tumors, 19FRI correlated with the reported radiobiological hypoxic fraction of
      the tumors (r = 0.988; P = 0.01). In addition, changes in tumor microenvironment
      were detected by 19F MRS. An increase in hypoxia induced by hydralazine treatment
      of RIF-1 tumor-bearing mice was associated with a 2.4-fold increase in 19FRI
      compared to untreated controls. In contrast, carbogen breathing by C3H mammary
      tumor-bearing mice produced a 6-fold decrease in the 19FRI compared to air
      breathing mice. The data presented support the preclinical and clinical
      development of SR-4554 as a noninvasive probe for tumor hypoxia.

PMID- 9242467
TI  - Correspondence re: F. Martini et al., SV40 early region and large T antigen in
      human brain tumors, peripheral blood cells, and sperm fluids from healthy
      individuals. Cancer Res., 56: 4820-4825, 1996.

PMID- 9242468
TI  - Colon cancer: the evolution of causal concepts.

PMID- 9242469
TI  - A case-control study of cytochrome P450 1A1, glutathione S-transferase M1,
      cigarette smoking and lung cancer susceptibility (Massachusetts, United States)
AB  - Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic
      polymorphisms are involved in the activation and detoxification of chemical
      carcinogens found in tobacco smoke; thus they may influence host susceptibility
      to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA)
      of 416 cases and 446 controls (mostly White) we evaluated the association between
      the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their
      interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was
      present in 18 percent of cases and 16 percent of controls, and one percent of
      cases and controls were CYP1A1 MspI homozygous variant. The GSTM1 null genotype
      was detected in 54 percent of cases and 52 percent of controls. After adjusting
      for age, gender, pack-years of smoking, and years since quitting smoking, while
      neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype
      alone were associated with a significant increase in lung cancer risk, having
      both genetic traits was associated with a twofold increase in risk (95 percent
      confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for
      a substantial modification of the effect of pack-years on lung cancer risk by the
      CYP1A1 MspI and GSTM1 genotypes. However, limitations of our study preclude a
      conclusion about this potential interaction.

PMID- 9242470
TI  - Polymorphisms in the glutathione S-transferase class mu and theta genes interact
      and increase susceptibility to lung cancer in minority populations (Texas, United
      States).
AB  - The genes coding for separate isoforms of both the human glutathione S
      transferase class mu and class theta enzymes (GSTM1 and GSTT1) are polymorphic
      with a variable ethnic distribution. These enzymes detoxify reactive epoxides,
      including carcinogens produced by tobacco smoke. Because of this, the null
      polymorphism in the GSTM1 gene (coding for the glutathione S-transferase class mu
      enzyme) has been studied widely as a possible source of inherited susceptibility
      to smoking-related lung cancer. The more recently described null polymorphism in
      the GSTT1 gene also could contribute to an increased risk of smoking-related lung
      cancer. As the incidence of lung cancer is known to differ by ethnicity, we have
      conducted a case-control study in the United States of 108 African-Americans
      (Blacks) and 60 Mexican-Americans (Hispanics) with lung cancer and 132 African
      American (Black) and 146 Mexican-American (Hispanic) controls to investigate the
      association of the GSTT1 and GSTM1 polymorphisms with lung cancer in minority
      populations. In the unadjusted data, there was a borderline significant
      association of the GSTM1 null polymorphism with lung cancer in Mexican-Americans
      (odds ratio [OR] = 1.8, 95 percent confidence interval [CI] = 1.0-3.3 ) that was
      not observed in African-Americans. The GSTT1 null polymorphism also had a higher
      prevalence in cases than controls in both racial/ethnic groups, but this increase
      was not statistically significant. When the data were analyzed using logistic
      regression controlling for age, gender, race, and smoking, no significant
      association of either trait with lung cancer was observed, with ORs for both
      traits of approximately 1.3. However, when the prevalence of individuals who were
      null for both polymorphisms was compared by case status, a significant
      interaction was observed. Logistic regression models showed the OR for the
      association of lung cancer and the presence of both null polymorphisms compared
      with one (either GSTT1 or GSTM1) or no null genotype to be 2.9 (P < 0.04). These
      results suggest that there may be carcinogenic intermediates in cigarette smoke
      that are substrates for both the GSTT1 and GSTM1 enzymes, and that lung cancer
      risk is increased more than additively for individuals who have both GSTT1 and
      GSTM1 null polymorphisms.

PMID- 9242471
TI  - Trends in urinary bladder cancer incidence in Sweden 1960-93 with special
      reference to histopathology, time period, birth cohort, and smoking.
AB  - This study investigates the incidence trends of urinary bladder cancer in Sweden
      from 1960 through 1993 (a total of 46,211 cases). Age-standardized incidence
      rates increased among men from 14.6 per 10(5) in 1960 to 33.5 in 1993 and among
      women from 4.8 to 8.8, corresponding to an average annual increase of 2.4 percent
      (95 percent confidence interval [CI]) = 2.0-2.7 percent) and 1.1 percent (CI =
      0.9-1.4 percent), respectively. The largest increase occurred in the oldest age
      groups. The proportion of patients with transitional cell carcinoma increased in
      men from 66.0 percent in 1960-64 to 93.6 percent in 1990-93 and in women from
      61.0 percent to 89.4 percent. The proportion of patients with papillomas
      decreased, whereas those with adenocarcinoma and squamous cell carcinoma were
      stable. Regression modeling (based on the period 1960-89) showed a strong linear
      effect due to either period and/or cohort. Among men, additional non-linear
      effects by both period and cohort were obtained. The cohort effects were more
      important. Cohort data on having smoked daily showed considerable similarities
      with the estimated cohort-effects. Our findings suggest that the increase of
      tobacco smoking in successive generations can explain the increase in incidence
      rates of bladder cancer in Sweden, whereas improved diagnostic activities and
      registration are less likely to explain fully the changes in incidence rates.

PMID- 9242472
TI  - Physical activity and risk of colon cancer: the Physicians' Health Study (United
      States).
AB  - Previous studies indicate that physical activity is related inversely to colon
      cancer risk. However, details regarding that association--whether a dose-response
      relation exists, whether the relation differs between non-obese and obese
      persons, the effect of long-term physical activity--are unclear. We examined
      these issues in the Physicians' Health Study (United States). Physical activity
      was assessed at baseline among 21,807 men, aged 40 to 84 years, and again 36
      months later. Men were followed for an average of 10.9 years (from baseline)
      during which 217 developed colon cancer. After adjusting for potential
      confounders (including age, obesity, and alcohol intake), the relative risks for
      colon cancer associated with vigorous exercise in times per week (< 1, 1, 2-4,
      5+, at baseline) were 1.0 (referent); 1.1 (95% confidence interval [CI] = 0.7
      1.7); 1.2 (CI = 0.8-1.6); and 1.1 (CI = 0.7-1.6), respectively; P trend = 0.6.
      Physical activity was not associated significantly with colon cancer risk either
      among non-obese or obese men. When we used physical activity assessments at
      baseline as well as at 36 months, physical activity again was unrelated to colon
      cancer risk. These data do not support the hypothesis that physical activity
      reduces the risk of colon cancer. Plausible alternate explanations for the null
      finding include misclassification of physical activity and the potential for
      increased surveillance for colon cancer ('screening effect') among those
      physically active.

PMID- 9242473
TI  - Plant foods and colon cancer: an assessment of specific foods and their related
      nutrients (United States).
AB  - Plant foods have been associated inversely with colon cancer. Since a major focus
      of this study was to identify components of plant foods which may account for
      their association with colon cancer, nutrients which are commonly found in plant
      foods also were evaluated. A population-based case-control study was conducted in
      Northern California, Utah, and the 'Twin Cities' area of Minnesota (United
      States). Complete data were available from interviewer-administered
      questionnaires on 1,993 cases and 2,410 controls. Higher intakes of vegetables
      (for highest relative to lowest quintile of intake) were associated inversely
      with colon cancer risk: the odds ratio (OR) was 0.7 for both men (95 percent [CI]
      confidence interval = 0.5-0.9) and women (CI = 0.5-1.0). Associations were
      stronger among those with proximal tumors. Total fruit intake was not associated
      with colon cancer risk although, among men, higher levels of whole grain intake
      were associated with a decreased risk (OR = 0.6, CI = 0.4-0.9 for older men);
      high intakes of refined grains were associated with an increased risk (OR = 1.5,
      CI = 1.1-2.1). Dietary fiber intake was associated with a decreased risk of colon
      cancer: OR = 0.5 (CI = 0.3-0.9) for older men; OR = 0.7 (CI = 0.4-1.2) for older
      women; OR = 0.6 (CI = 0.4-1.0) for men with proximal tumors; OR = 0.5 (CI = 0.3
      0.9) for women with proximal tumors. Other nutrients, for which plant foods were
      the major contributor--such as vitamin B6, thiamin, and niacin (women only)--also
      were associated inversely with colon cancer. Neither beta-carotene nor vitamin C
      was protective for colon cancer. Adjustment of plant foods for nutrients found in
      plant foods or for supplement use did not appreciably alter the observed
      associations between plant foods and colon cancer.

PMID- 9242474
TI  - Adult height and incidence of cancer in male physicians (United States).
AB  - Adult height has been found in some but not all studies to be associated
      positively with overall cancer incidence as well as several site-specific
      cancers. The Physicians' Health Study (PHS), a randomized trial of beta-carotene
      and aspirin in the primary prevention of cancer and cardiovascular disease in
      men, provided an opportunity to examine the association between height and total
      malignant neoplasms (excluding non-melanoma skin cancer), as well as site
      specific cancers including prostate, colorectal, and lung cancer. The PHS is
      comprised of 22,071 US male physicians in the United States, a population
      homogeneous for adult socioeconomic status, aged 40 to 84 years in 1982.
      Participants were classified into five height categories at study entry. After an
      average follow-up of over 12 years, there were 2,566 cases of incident total
      malignant neoplasms, including 1,047 prostate, 341 colorectal, and 170 lung
      cancer cases. Height was associated positively with both total malignant
      neoplasms and prostate cancer. Compared with men in the shortest category (<67
      inches), relative risks and 95 percent confidence intervals (CI) for total
      malignant neoplasms for men whose height (in inches) was 68-69, 70-71, 72, and
      73+ were, respectively: 1.13 (CI = 0.99-1.28), 1.15 (CI = 1.02-1.30), 1.29 (CI =
      1.12-1.49), and 1.21 (CI = 1.05-1.39), P trend 0.001, adjusted for age,
      randomized treatment assignments, body mass index (wt/ht2), cigarette smoking,
      alcohol use, and exercise frequency. For prostate cancer, the corresponding RR
      values were 1.23 (CI = 1.00-1.51), 1.26 (CI = 1.04-1.54), 1.59 (CI = 1.27-1.98),
      and 1.26 (CI = 1.00-1.59), P trend 0.005. For colorectal cancer, in some but not
      all height categories compared with the shortest, there were elevated RRs without
      a significant linear trend: RR = 1.51 (CI = 1.06-2.14), 1.14 (CI = 0.80-1.62),
      1.19 (CI = 0.79-1.80), and 1.53 (CI = 1.04-2.25), P trend 0.23. In contrast,
      there was no evidence of an association of height with lung cancer. These data
      indicate a positive association between height and risk of total malignant
      neoplasms, as well as of prostate cancer and, possibly, colorectal cancer.

PMID- 9242475
TI  - Risk factor information found in medical records of lung and prostate cancer
      cases, New Mexico Tumor Registry (United States).
AB  - The conduct of public health surveillance and epidemiologic investigations would
      be enhanced by a cost-effective method for the collection of population-based
      cancer risk-factor data. We assessed the feasibility of ascertaining such data
      from hospital medical records during routine abstraction of information from a
      cancer registry. We examined the medical records of a representative sample of
      prostate and lung cancer cases diagnosed during 1992 and 1993 from the New Mexico
      (United States) Tumor Registry (NMTR) database. Registry personnel abstracted
      ancillary information from the medical records of 575 prostate and 273 lung
      cancer cases. Of medical records from 848 cases, 90 percent documented a history
      of tobacco use, 77 percent contained any family medical history, and 48 percent
      documented occupational information sufficient to allow coding into standard
      occupational groups. Availability of occupation and industry varied by patient
      ethnicity, age at diagnosis, marital status, and type of hospital, indicating the
      potential for bias in studies using occupational information from medical
      records. Our findings suggest that risk factor information abstracted from
      medical records may provide valuable information for public health surveillance,
      but is generally too incomplete to serve as a single source of exposure
      information for etiologic studies. Family histories in medical records may be
      sufficient for population-based ascertainment of affected relative pairs for
      genetic epidemiology studies for some cancer types.

PMID- 9242476
TI  - Drinking practices and risk of squamous-cell esophageal cancer among Black and
      White men in the United States.
AB  - To evaluate whether the fivefold greater incidence rate of squamous-cell
      esophageal cancer in Black compared with White men is due to type of alcoholic
      beverage consumed or to other qualitative differences in alcohol consumption, we
      conducted a population-based case-control study with 373 males diagnosed with
      squamous-cell esophageal cancer (124 Whites and 249 Blacks) and 1,364 male
      controls (750 Whites and 614 Blacks) from three geographic areas in the United
      States. Included were all histologically confirmed cases newly diagnosed from 1
      August 1986 through 30 April 1989, among White and Black men aged 30 to 79 years.
      Risks varied to some extent according to type of alcohol used, with beer a
      stronger contributor in Whites, and wine and liquor stronger contributors in
      Blacks. However, most of the differences in the odds ratios by type of alcohol
      and race were eliminated after controlling for average weekly amount of total
      alcohol consumed. Thus, while alcohol use in all forms is an important risk
      factor for squamous-cell esophageal cancer in Whites and Blacks, type of
      alcoholic beverage used does not appear to account for the racial differences in
      incidence.

PMID- 9242477
TI  - Multiple myeloma among Blacks and Whites in the United States: role of cigarettes
      and alcoholic beverages.
AB  - In the United States, the incidence rates of multiple myeloma in Blacks are more
      than twice those in Whites, but the etiology of this cancer is poorly understood.
      A population-based case-control interview study of 571 subjects (365 White, 206
      Black) with multiple myeloma and 2,122 controls (1,155 White, 967 Black) living
      in three areas of the United States (Georgia, Michigan, New Jersey) offered the
      opportunity to investigate the relationship with smoking and alcohol drinking and
      to evaluate whether these factors might contribute to the excess risk of multiple
      myeloma in Blacks. For Blacks and Whites of either gender, there were no
      significantly elevated risks associated with ever use of cigarettes or alcoholic
      beverages and no consistent patterns with either intensity or duration of use.
      These data support previous studies indicating that smoking and drinking are not
      related causally to the risk of multiple myeloma, and thus cannot account for the
      racial disparity in incidence rates.

PMID- 9242478
TI  - Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal
      cancer in Finnish men.
AB  - Experimental and human epidemiologic data suggest a protective role for vitamin D
      in large bowel cancer. To investigate this association, we conducted a nested
      case-control study within a Finnish clinical trial cohort. Cases (n = 146) were
      participants diagnosed with primary adenocarcinoma of the large bowel. Controls
      were matched (2:1) to cases on age, date of baseline blood draw, and study
      clinic. Prediagnostic serum levels of the vitamin D metabolites, 25
      hydroxyvitamin D (25-OH D), and 1,25-dihydroxyvitamin D (1,25-DIOH D) were used
      as primary exposure measures. The baseline geometric-mean serum level of 25-OH D
      was 11.6 percent lower in cases than in controls (12.2 cf 13.8 ug/l, P = 0.01)
      while serum levels of 1,25-DIOH D did not differ by case-control status. No
      association was seen between serum levels of 1,25-DIOH D and large bowel cancer
      risk. However, the estimated relative risk (RR) of large bowel cancer decreased
      with increasing level of serum 25-OH D and the association was more pronounced
      for rectal cancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P =
      0.06). Neither exclusion of early cases nor multivariate adjustment for potential
      confounders materially altered these estimates. There was no evidence of effect
      modification by level of 1,25-dihydroxyvitamin D or with other known risk-factors
      for large bowel cancer.

PMID- 9242479
TI  - Physical activity in usual occupation and risk of breast cancer (United States).
AB  - We have used data from a large population-based case-control study in the United
      States to evaluate the effect of occupational physical activity on breast cancer
      risk. Women diagnosed with breast cancer identified from four state cancer
      registries, and controls randomly selected from lists of licensed drivers or
      Medicare beneficiaries, were interviewed by telephone for information on usual
      occupation and other factors. We classified usual occupation into one of four
      categories of physical activity. After excluding subjects for whom a strength
      rating could not be assigned, we had a final sample size of 4,863 cases and 6,783
      controls. Using conditional logistic regression models, we calculated adjusted
      odds ratios (OR) and 95 percent confidence intervals (CI) for occupations having
      light, medium, and heavy activity compared with sedentary ones. Women with heavy
      activity occupations had a lower risk of breast cancer than women with sedentary
      jobs (OR = 0.82, CI = 0.63-1.08), as did women with jobs with medium activity (OR
      = 0.86, CI = 0.77-0.97) or light activity (OR = 0.92, CI = 0.84-1.01). There was
      a significant decreasing trend in the ORs from sedentary to heavy work (P =
      0.007). Although limited by exposure misclassification, these data are consistent
      with the hypothesis that physical activity reduces the risk of breast cancer.

PMID- 9242480
TI  - Serum steroids in relation to prostate cancer risk in a case-control study
      (Greece).
AB  - Blood samples were collected from 52 incident cases of histologically confirmed
      prostate cancer and 52 age- and town of residence-matched healthy controls in
      Athens, Greece. Samples were analyzed blindly in Boston, Massachusetts (USA) for
      testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), and
      dihydrotestosterone (DHT). The data were modeled using multiple logistic
      regression with adjustment for age, height, body mass index (wt/ht2), years of
      schooling, and mutually among hormones. DHT was associated inversely,
      significantly, and strongly with the risk of prostate cancer, whereas T was
      associated marginally positively, and E2 was associated nonsignificantly
      inversely with the disease. No association was observed in this study with
      respect to SHBG.

PMID- 9242481
TI  - A case-control study of diet and colorectal cancer in a multiethnic population in
      Hawaii (United States): lipids and foods of animal origin.
AB  - Temporal trend and migrant studies have indicated that the etiology of colorectal
      cancer is predominantly environmental and, hence, modifiable. Animal fat intake
      has been frequently, but inconsistently, associated with the risk of this
      disease. We conducted a population-based case-control study in Hawaii (United
      States) among ethnic groups at different risks of the disease to evaluate the
      role of dietary lipids and foods of animal origin on the risk of colorectal
      cancer. We interviewed 698 male and 494 female Japanese, Caucasian (White),
      Filipino, Hawaiian, and Chinese patients diagnosed during 1987-91 with
      pathologically confirmed adenocarcinoma of the colon or rectum, and 1,192
      population controls matched to cases on age, gender and ethnicity. Odds ratios
      (OR), adjusted for caloric intake and other dietary and non-dietary risk factors,
      were estimated using conditional logistic regression. Intakes of total fat,
      saturated fat (S) and polyunsaturated fat (P) were not related to the risk of
      colorectal cancer. However, an inverse association was found for the P/S ratio,
      with ORs of 0.6 in both genders (95 percent confidence interval [CI] = 0.4-1.0
      for males; CI = 0.3-0.9 for females) for the highest compared with the lowest
      quartile (P < 0.05 for trend). Intakes of red meat and processed meat were
      associated with the risk of cancer in the right colon and rectum, respectively,
      in men only. Fat-trimmed red meat and fish intakes were not related to risk.
      Chicken eaten without skin was associated inversely with risk in both genders.
      The strongest association was found for eggs, with an OR of 2.7 (CI = 1.7-4.0)
      and 2.3 (CI = 1.4-3.7) for the highest compared with the lowest quartile of
      intake in men and women, respectively (P < 0.001 for trend). This association was
      dose-dependent, not explained by known confounders or other dietary variables,
      and was very consistent between genders, among ethnic groups, and across all
      segments of the large bowel. These data suggest that the ratio of polyunsaturated
      to saturated fat may be a better indicator of colorectal cancer risk than the
      absolute amount of specific fats in the diet. They also suggest that eggs and,
      possibly, untrimmed red meat and processed meat increase, and chicken eaten
      without skin decreases, colorectal cancer risk.

PMID- 9242482
TI  - Physical activity and reduced risk of colon cancer: implications for prevention.
AB  - This paper reviews the consistency of the relation between increased physical
      activity and reduced risk of colon cancer, estimates the potential prevention
      benefit from increasing population levels of physical activity, and considers
      social strategies to increase activity levels. The published literature was
      reviewed systematically and supplemented by MEDLINE searches through March 1997.
      Studies that reported a measure of physical activity and outcomes of colon cancer
      or colorectal cancer were included. We excluded the first report of a study that
      was expanded subsequently by extended follow-up, and any study that did not
      report the methods for measurement of physical activity. Data were extracted
      including details on study size, methods of classifying physical activity, and
      outcomes. A consistent inverse relation was observed such that increased physical
      activity was associated with reduced risk of colon cancer. About a 50 percent
      reduction in incidence was observed among those with the highest level of
      activity across numerous studies that used different measures of activity
      (occupational or leisure-time activity). This association persisted in studies
      using multivariate analyses to control for diet and other known or suspected risk
      factors for colon cancer. Risk reduction was attenuated in those studies that
      combined colon and rectal cancer. This review indicates that greater attention
      should be placed on social strategies to increase physical activity as a means of
      preventing colon cancer.

PMID- 9242483
TI  - Research questions concerning prostate cancer screening.

PMID- 9242484
TI  - Hormone replacement therapy and early clinical appearance of low grade breast
      cancer.

PMID- 9242485
TI  - Survival in a cruel world: how Vibrio cholerae and Salmonella respond to an
      unwilling host.

PMID- 9242486
TI  - Cdc37 is a molecular chaperone with specific functions in signal transduction.
AB  - Cdc37 is required for cyclin-dependent kinase activation and is genetically
      linked with the activity of several other kinases, including oncogenic v-Src,
      casein kinase II, MPS-1 kinase, and sevenless. Strikingly, many pathways
      involving Cdc37 also involve the protein chaperone Hsp90. The identification of
      Cdc37 as the 50-kD protein in several Hsp90-kinase complexes, together with other
      data, led to the recent suggestion that Cdc37 is a kinase-targeting "subunit" of
      Hsp90. We directly examined the effect of Cdc37 on Hsp90 functions. Rather than
      simply acting as an accessory factor for Hsp90, Cdc37 is itself a protein
      chaperone with properties remarkably similar to those of Hsp90. In vitro, Cdc37
      maintains denatured beta-galactosidase in an activation-competent state without
      reactivating it and stabilizes mature, but unstable, casein kinase II. In vivo,
      Cdc37 overexpression can compensate for decreased Hsp90 function, but the
      proteins are not interchangeable. Cdc37 can compensate for Hsp90 in maintaining
      the activity of v-Src kinase but does not maintain the activity of the
      glucocorticoid receptor. Thus, the very similar chaperone activities of the two
      proteins, uncovered through in vitro analysis, diverge in vivo in specific signal
      transduction pathways.

PMID- 9242487
TI  - Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and
      crossover interference.
AB  - The TAM1 gene of Saccharomyces cerevisiae is expressed specifically during
      meiosis and encodes a protein that localizes to the ends of meiotic chromosomes.
      In a tam1 null mutant, there is an increase in the frequency of chromosomes that
      fail to recombine and an associated increase in homolog nondisjunction at meiosis
      I. The tam1 mutant also displays an increased frequency of precocious separation
      of sister chromatids and a reduced efficiency of distributive disjunction. The
      defect in distributive disjunction may be attributable to overloading of the
      distributive system by the increased number of nonrecombinant chromosomes.
      Recombination is not impaired in the tam1 mutant, but crossover interference is
      reduced substantially. In addition, chromosome synapsis is delayed in tam1
      strains. The combination of a defect in synapsis and a reduction in interference
      is consistent with previous studies suggesting a role for the synaptonemal
      complex in regulating crossover distribution. tam1 is the only known yeast mutant
      in which the control of crossover distribution is impaired, but the frequency of
      crossing over is unaffected. We discuss here possibilities for how a telomere
      associated protein might function in chromosome synapsis and crossover
      interference.

PMID- 9242488
TI  - The UNC-14 protein required for axonal elongation and guidance in Caenorhabditis
      elegans interacts with the serine/threonine kinase UNC-51.
AB  - Certain unc mutants in the nematode Caenorhabditis elegans, such as unc-14 and
      unc-51, show abnormal axonal elongation and axonal structures. We cloned the unc
      51 gene previously and predicted that it encodes a novel serine/threonine protein
      kinase. In this study, we precisely localized the activity to rescue an unc-14
      mutation. Also, we identified four cDNA clones encoded by the unc-14 rescuing
      region, in screens for proteins that bind to UNC-51 using a yeast two-hybrid
      system. A mutation site in the cDNA was identified for each of the six unc-14
      mutants, establishing that the unc-14 gene was cloned. The unc-14 gene encodes a
      novel protein of 665 amino acids, and is coexpressed with the unc-51 gene in the
      cell bodies and axons of almost all neurons including DD/VD and hermaphrodite
      specific neurons. Another clone recovered in the two-hybrid screen encodes a
      carboxy-terminal region of UNC-51. Analysis using the yeast two-hybrid system
      suggested that a central region of UNC-14 bound to a carboxy-terminal region of
      UNC-51, and that the UNC-51 carboxy-terminal region oligomerized. In in vitro
      binding studies using recombinant fusion proteins, UNC-14 interacted with UNC-51
      directly. We propose that UNC-51 protein kinase acts as an oligomer, and that UNC
      14 is a regulator of UNC-51, in axonal elongation and guidance.

PMID- 9242489
TI  - The signaling pathway mediated by the type IIB activin receptor controls axial
      patterning and lateral asymmetry in the mouse.
AB  - Vertebrate animals exhibit segmented axial skeletons and lateral asymmetry of the
      visceral organs. The segment identity of individual vertebrae is believed to be
      determined by a combination of functionally active Hox genes that have defined
      expression boundaries along the anteroposterior axis (known as the axial Hox
      code). Disturbance of the Hox code by ectopic expression or mutation of Hox genes
      often leads to homeotic transformation of the vertebrae. Largely unknown,
      however, are the signaling molecules that provide the positional cues for the
      precise establishment and maintenance of the Hox code. In this study we show that
      disruption of the type IIB activin receptor (ActRIIB) by gene targeting results
      in altered expression of multiple Hox genes and abnormal patterning of the
      vertebrae, similar to but severer than retinoic acid (RA)-induced anterior
      transformation. We further show that RA and ActRIIB mutation have synergistic
      effects on vertebral patterning. Activin, Vg-1 and, type II activin receptors
      have been implicated in regulation of lateral asymmetry during chick and Xenopus
      development. We show here that the ActRIIB-/- mice die after birth with
      complicated cardiac defects including randomized heart position, malposition of
      the great arteries, and ventricular and atrial septal defects. In addition, the
      heart anomalies are associated with right pulmonary isomerism and splenic
      abnormalities, recapitulating the clinical symptoms of the human asplenia
      syndrome. These findings provide genetic evidence that the ActRIIB-mediated
      signaling pathway plays a critical role in patterning both anteroposterior and
      left-right axes in vertebrate animals.

PMID- 9242490
TI  - Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential
      for segmentation initiation.
AB  - We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross
      hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed
      in the rostral presomitic mesoderm, but down-regulated immediately after the
      formation of the segmented somites. To determine the function of MesP2 protein
      (MesP2) in somitogenesis, we generated Mesp2-deficient mice by gene targeting.
      The homozygous Mesp2 (-/-) mice died shortly after birth and had fused vertebral
      columns and dorsal root ganglia, with impaired sclerotomal polarity. The earliest
      defect in the homozygous embryos was a lack of segmented somites. Their
      disruption of the metameric features, altered expression of Mox-1, Pax-1, and
      Dll1, and lack of expression of Notch1, Notch2, and FGFR1 suggested that MesP2
      controls sclerotomal polarity by regulating the signaling systems mediated by
      notch-delta and FGF, which are essential for segmentation.

PMID- 9242491
TI  - E2F1-induced apoptosis requires DNA binding but not transactivation and is
      inhibited by the retinoblastoma protein through direct interaction.
AB  - E2F1 overexpression has been shown to induce apoptosis in cooperation with p53.
      Using Saos-2 cells, which are null for p53 and lack functional Rb, we have
      demonstrated that E2F1 overexpression can also induce apoptosis in the absence of
      p53 and retinoblastoma protein (Rb). E2F1-induced apoptosis can be specifically
      inhibited by Rb but not mdm2, which is known for its ability to inhibit p53
      induced apoptosis. Through the study of the apoptotic function of a set of E2F1
      mutants, it was clear that the transactivation and the apoptotic function of E2F1
      are uncoupled. The transactivation-defective E2F1 mutants E2F1(1-374), E2F1(390
      1)DF(delta mdm2), and E2F1(406-415)(delta Rb) can induce apoptosis as effectively
      as wild-type E2F1. In contrast to E2F1 transactivation, the DNA-binding activity
      of E2F1 was proven to be essential for its apoptotic function, as the DNA-binding
      defective mutants E2F1(132) and E2F1(132)(1-374) failed to induce apoptosis.
      Therefore Rb may inhibit E2F1-induced apoptosis by mechanisms other than the
      suppression of the transactivation of E2F1. This hypothesis was supported by our
      observation that although Rb overexpression can specifically repress the
      apoptosis induced by wild-type E2F1 and a Rb-binding-competent E2F1 mutant
      E2F1(390-1)DF(delta mdm2), it failed to inhibit the apoptosis induced by mutants
      E2F1(1-374) and E2F1(delta 406-415)(delta Rb), which are defective or reduced in
      Rb binding and transactivation. All of these points argue for a novel function
      for E2F1 and Rb in controlling apoptosis. The results also indicate that
      transcriptional repression rather than the transactivation function of E2F1 may
      be involved in its apoptotic function. The results presented here may provide us
      some physiological implication of the repression function of the Rb-E2F1 complex.

PMID- 9242492
TI  - Induction of DNA synthesis and apoptosis are separable functions of E2F-1.
AB  - The family of E2F transcription factors have an essential role in mediating cell
      cycle progression, and recently, one of the E2F protein family, E2F-1, has been
      shown to participate in the induction of apoptosis. Cooperation between E2F and
      the p53 tumor suppressor protein in this apoptotic response had led to the
      suggestion that cell cycle progression induced by E2F-1 expression provides an
      apoptotic signal when placed in conflict with an arrest to cell cycle
      progression, such as provided by p53. We show here that although apoptosis is
      clearly enhanced by p53, E2F-1 can induce significant apoptosis in the absence of
      p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability
      to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that
      although DNA-binding is required, transcriptional transactivation is not
      necessary for the induction of apoptosis by E2F-1, suggesting that it may be
      mediated through alleviation of E2F-dependent transcriptional repression. These
      results indicate that E2F-1 can show independent cell cycle progression and
      apoptotic functions, consistent with its putative role as a tumor suppressor.

PMID- 9242493
TI  - U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP
      branchpoint interaction.
AB  - Splicing of mRNA precursors (pre-mRNAs) comprises a series of ATP-dependent
      steps, the first of which is the stable binding of U2 snRNP at the pre-mRNA
      branchpoint. The basis of ATP use for the interaction between U2 snRNP and the
      branchpoint is unclear, and, in particular, none of the known mammalian factors
      required for this step have the sequence characteristics of proteins that
      hydrolyze ATP. Entry of U2 snRNP into the spliceosome is initiated by interaction
      of the essential splicing factor U2AF65 with the pre-mRNA polypyrimidine tract.
      In this report we identify a new region of U2AF65 required for function, and use
      this information to clone a human 56-kD U2AF65 associated protein (UAP56). We
      show that UAP56 is an essential splicing factor, which is recruited to the pre
      mRNA dependent on U2AF65, and is required for the U2 snRNP-branchpoint
      interaction. The sequence of UAP56 indicates it is a member of the DEAD box
      family of RNA-dependent ATPases, which mediate ATP hydrolysis during several
      steps of yeast pre-mRNA splicing. Our results reveal a new function of U2AF65: to
      position a DEAD box protein required for U2 snRNP binding at the pre-mRNA
      branchpoint region.

PMID- 9242494
TI  - Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal
      differentiation.
AB  - Here we report on investigation of the role of the POU domain genes Skin-1a/i
      (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where
      proliferating basal keratinocytes withdraw from the cell cycle, migrate
      suprabasally, and terminally differentiate to form a multilayered, stratified
      epithelium. The expression of the Skn-1a/i and Tst-1 genes is linked to
      keratinocyte differentiation in vivo and in vitro, whereas the ubiquitous POU
      domain factor Oct-1 is expressed highly in both proliferating and post-mitotic
      keratinocytes. Analysis of Skn-1a/i gene-deleted mice reveals that the Skn-1a/i
      gene modulates the pattern of expression of the terminal differentiation marker
      loricrin and inhibits expression of genes encoding markers of the epidermal
      keratinocyte wounding response. Although epidermis from Tst-1 gene-deleted mice
      develops normally, epidermis from mice deleted for both Skn-1a/i and Tst-1 is
      hyperplastic and fails to suppress expression of K14 and Spr-1 in suprabasal
      cells when transplanted onto athymic mice. This suggests that Skn-1a/i and Tst-1
      serve redundant functions in epidermis. Therefore, at least two POU domain genes,
      Skn-1a/i and Tst-1, serve both distinct and overlapping functions to regulate
      differentiation of epidermal keratinocytes during normal development and wound
      healing.

PMID- 9242495
TI  - Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere
      4 is regulated by Hoxb1.
AB  - Correct regulation of the segment-restricted patterns of Hox gene expression is
      essential for proper patterning of the vertebrate hindbrain. We have examined the
      molecular basis of restricted expression of Hoxb2 in rhombomere 4 (r4), by using
      deletion analysis in transgenic mice to identify an r4 enhancer from the mouse
      gene. A bipartite Hox/Pbx binding motif is located within this enhancer, and in
      vitro DNA binding experiments showed that the vertebrate labial-related protein
      Hoxb1 will cooperatively bind to this site in a Pbx/Exd-dependent manner. The
      Hoxb2 r4 enhancer can be transactivated in vivo by the ectopic expression of
      Hoxb1, Hoxa1, and Drosophila labial in transgenic mice. In contrast, ectopic
      Hoxb2 and Hoxb4 are unable to induce expression, indicating that in vivo this
      enhancer preferentially responds to labial family members. Mutational analysis
      demonstrated that the bipartite Hox/Pbx motif is required for r4 enhancer
      activity and the responses to retinoids and ectopic Hox expression. Furthermore,
      three copies of the Hoxb2 motif are sufficient to mediate r4 expression in
      transgenic mouse embryos and a labial pattern in Drosophila embryos. This
      reporter expression in Drosophila embryos is dependent upon endogenous labial and
      exd, suggesting that the ability of this Hox/Pbx site to interact with labial
      related proteins has been evolutionarily conserved. The endogenous Hoxb2 gene is
      no longer upregulated in r4 in Hoxb1 homozygous mutant embryos. On the basis of
      these experiments we conclude that the r4-restricted domain of Hoxb2 in the
      hindbrain is the result of a direct cross-regulatory interaction by Hoxb1
      involving vertebrate Pbx proteins as cofactors. This suggests that part of the
      functional role of Hoxb1 in maintaining r4 identity may be mediated by the Hoxb2
      gene.

PMID- 9242496
TI  - Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular
      dermatosis type of IgA pemphigus.
AB  - IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is
      divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic
      IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from
      some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human
      Dsc. To determine the antigen for IgA pemphigus, we focused on conformation
      dependent epitopes of Dsc, because sera of patients with classical pemphigus
      recognize conformation-sensitive epitopes of desmogleins. We constructed
      mammalian expression vectors containing the entire coding sequences of human
      Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by
      lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs
      showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with
      the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3.
      In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells
      transfected with any Dscs. These results convincingly indicate that human Dsc1 is
      an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an
      important role for Dsc1 in the pathogenesis of this disease. This study shows
      that a Dsc can be an autoimmune target in human skin disease.

PMID- 9242497
TI  - Reduced expression of PDGF and PDGF receptors during impaired wound healing.
AB  - A series of studies has shown that application of platelet-derived growth factor
      (PDGF) to a wound enhances the process of wound repair, especially in animals
      with wound-healing defects. In the current study, we investigated the regulation
      of PDGF A and PDGF B and their receptors during wound repair in mice. Both
      ligands and both types of receptor were expressed in normal and wounded skin,
      whereby PDGF A and PDGF B proteins were found at different sites in the healing
      wound. Surprisingly, no significant induction of these genes was observed after
      skin injury in normal mice, and expression levels were similar at all stages of
      the repair process. To determine a possible role of endogenous PDGF in normal
      wound healing, we subsequently analyzed the regulation of PDGF and PDGF receptors
      during wound healing in healing-impaired animals. Genetically diabetic db/db mice
      showed a significant reduction in PDGF A and A-type receptor expression in
      nonwounded and wounded back skin. Furthermore, expression of the B-type receptor
      was also reduced during the repair process. Systemic glucocorticoid treatment
      caused a severe defect in wound repair that was accompanied by reduced expression
      of PDGF A and B and of the B-type receptor in the early phase of wound healing.
      These results provide an explanation for the beneficial effect of exogenous PDGF
      in the treatment of wound-healing disorders. Furthermore, our data suggest that a
      certain expression level of PDGF and its receptors is essential for normal
      repair.

PMID- 9242498
TI  - An ex vivo keratinocyte model for gene therapy of hemophilia B.
AB  - We are investigating whether skin-targeted gene therapy may be used to treat
      hemophilia B by transplanting keratinocytes transduced by factor IX-expressing
      retroviral vectors. No pre-clinical animal model for keratinocyte-mediated gene
      therapy has shown long-term efficacy in vivo. It remains unclear whether this
      short-term expression is due to promoter shut-off or a reduced survival of
      grafted genetically modified cells. The purpose of this study was to determine
      the fate of primary human keratinocytes superficially grafted to nude mice in a
      silicone transplantation chamber. In addition, vectors containing keratinocyte
      specific enhancers from the human papilloma virus-16 (HPV-16) and human keratin 5
      and 14 genes were used upstream of the cytomegaloviral (CMV) immediate-early
      promoter/enhancer to control factor IX cDNA expression to avoid promoter shut
      off. Factor IX was secreted by cultured keratinocytes after transduction by each
      of these chimeric promoter/enhancer vectors, although the levels varied according
      to the particular construct used. Keratinocytes transduced by the vector
      containing the HPV-16 enhancer were grafted into nude mice, and human factor IX
      was detected in plasma at 0.02-9 ng per ml for 4-5 wk for the duration of graft
      survival. The HPV-16 enhancer may be a useful addition to expression vectors for
      keratinocyte gene therapy. The transplantation chamber can be adapted to grafting
      retrovirally transduced keratinocytes for gene transfer studies.

PMID- 9242499
TI  - Broad-spectrum sunscreens provide greater protection against ultraviolet
      radiation-induced suppression of contact hypersensitivity to a recall antigen in
      humans.
AB  - This study investigates the extent to which sunscreens protect humans from
      ultraviolet (UV)-radiation-induced immunosuppression. In the presence of solar
      simulated UV, three sunscreens with differing UVA transmission were assessed for
      their ability to protect the contact hypersensitivity (CHS) response to nickel of
      16 nickel-allergic subjects. The sunscreens contained 2-ethylhexyl para
      methoxycinnamate (cinnamate), cinnamate with oxybenzone, or cinnamate with zinc
      oxide, respectively. All had sun protection factors of 10 and hence inhibited UV
      erythema to similar extents. Volunteers were irradiated on their backs with
      suberythemal UV daily for 5 d after application of the sunscreens and their base
      lotion to different sites. Nickel-containing patches were then applied to both UV
      treated sites and adjacent, unirradiated control sites. Erythema caused by nickel
      CHS at each site was quantitated 72 h later with a reflectance erythema meter. In
      comparison of the nickel reactions of irradiated and unirradiated skin, there was
      35% mean immunosuppression in unprotected UV-treated skin. Significant
      immunosuppression also occurred at sites irradiated through the narrow-spectrum
      cinnamate-only sunscreen but was prevented by the two broad-spectrum sunscreens.
      To determine whether UV-induced suppression of the nickel response is specific
      for cell-mediated immunity or reflects suppression of nonspecific inflammation, a
      further 16 subjects were patch-tested with a skin irritant, sodium lauryl sulfate
      (SLS), following a sunscreen and irradiation protocol identical to that of the
      nickel volunteers. UV had no significant effect on SLS responses. We conclude
      that nickel patch testing is a valid means of assessing UV-induced
      immunosuppression in humans and that even with suberythemal UV, immune protection
      was provided only by sunscreens filtering both UVA and UVB.

PMID- 9242500
TI  - Growth suppression of hamster flank organs by topical application of gamma
      linolenic and other fatty acid inhibitors of 5alpha-reductase.
AB  - Certain unsaturated aliphatic fatty acids, such as gamma-linolenic acid, inhibit
      5alpha-reductase activity in vitro and in vivo. Hamster flank organ growth, as
      measured by the increase in the area of pigmented macule, is dependent on
      androgen. When one of the paired flank organs of a castrated hamster was treated
      topically with testosterone, the treated organ, but not the contralateral flank
      organ, became larger and darker. Topical application of gamma-linolenic acid to
      the testosterone-treated flank organ suppressed this testosterone effect. Other
      fatty acids that were not inhibitors of 5alpha-reductases were not active.
      Topical treatment of hamster flank organs with 5alpha-dihydrotestosterone also
      stimulated the growth of the organ. This 5alpha-dihydrotestosterone-dependent
      activity, however, was not significantly affected by gamma-linolenic acid,
      suggesting that flank organ growth was dependent on 5alpha-dihydrotestosterone
      and that gamma-linolenic acid acted by inhibiting 5alpha-reductase. With intact
      male hamsters, the endogenous androgen-dependent growth of flank organs is also
      suppressed by topical treatment with gamma-linolenic acid. The effect of gamma
      linolenic acid is localized at the site of its application; topical application
      of gamma-linolenic acid did not affect the androgen-dependent growth of other
      organs such as testis, epididymis, seminal vesicle, and prostate. gamma-Linolenic
      acid, with low toxicity and absence of systemic effect, therefore may be
      potentially useful for treatment of androgen-dependent skin disorders.

PMID- 9242501
TI  - Antagonistic effects of interferon-gamma and interleukin-4 on fibroblast
      cultures.
AB  - A major characteristic of scleroderma (SSc) fibroblasts is an increased
      biosynthesis of extracellular matrix macromolecules that could be linked to
      impaired regulation by cytokines. We investigated the effects of two cytokines
      from T lymphocytes, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), on
      normal and scleroderma fibroblast cultures. In both types of fibroblasts, IL-4
      strongly stimulated collagen synthesis, whereas IFN-gamma was a potent inhibitor.
      The effects of these cytokines were localized at the pre-translational level, and
      both mRNA steady-state level and protein synthesis were equally affected. SSc
      fibroblasts responded to IL-4 and IFN-gamma as well as normal fibroblasts. When
      fibroblasts were incubated with combinations of both cytokines, IFN-gamma
      completely suppressed the stimulation of collagen gene expression induced by IL
      4. Northern blot and western blot analyses demonstrated that IFN-gamma induced a
      rapid and strong decrease in the expression of the IL-4 receptor-alpha by
      fibroblasts. This effect might explain the antagonistic effects of IFN-gamma on
      the IL-4-dependent enhancement of collagen synthesis. Thus, our data suggest that
      the alteration of collagen production in scleroderma fibroblasts does not depend
      on an altered sensitivity of these cells to stimulatory or inhibitory cytokines
      but is more likely the consequence of an imbalance in the local production of
      autocrine or paracrine regulatory factors.

PMID- 9242502
TI  - Two pathways for induction of apoptosis by ultraviolet radiation in cultured
      human keratinocytes.
AB  - Loss of attachment may induce apoptosis in epithelial cells, but it is unclear
      whether substrate adhesion modulates apoptosis triggered by genotoxic agents such
      as ultraviolet radiation (UV). To investigate this issue, we plated neonatal
      human keratinocytes on different substrates and irradiated them with UVB. DNA
      strand breaks were nick-labeled to identify apoptotic nuclei. Keratinocytes grown
      in monolayers were less susceptible to UV-induced apoptosis than were cells
      freshly seeded on glass (ED50 2130 +/- 96 J per m2, mean +/- SD, versus 131 +/-
      96 J per m2, mean +/- SD, respectively). This phenomenon depended on differences
      in integrin-mediated adhesion, because blocking of integrin beta1 with a
      monoclonal antibody increased sensitivity of keratinocyte monolayers to UV and an
      increase in beta1 integrin receptor occupancy by plating on fibronectin, type IV
      collagen, or keratinocyte-derived extracellular matrix diminished the UV
      dependent apoptosis. Down-regulation of p53 with an anti-sense oligonucleotide
      did not affect apoptosis in glass-plated keratinocytes but effectively suppressed
      apoptosis in keratinocytes adhering via beta1 integrin. Thus, in addition to the
      known p53-dependent pathway, UV was able to induce a p53-independent apoptosis
      that could be blocked by integrin-mediated cell attachment (the integrin
      sensitive pathway). The susceptibility to the p53-dependent apoptosis, but not to
      the integrin-sensitive process, varied among keratinocytes of different
      clonogenic potential: transit amplifying cells > stem cells > terminally
      differentiated cells. The p53-independent integrin-sensitive apoptotic pathway
      may provide an additional mechanism counteracting UV carcinogenesis in the skin.

PMID- 9242503
TI  - Commercial tanning bed treatment is an effective psoriasis treatment: results
      from an uncontrolled clinical trial.
AB  - Phototherapy is highly effective in the therapy of psoriasis, but patient access
      to phototherapeutic facilities is not universal. Commercial tanning facilities
      are universal, but their efficacy in psoriasis treatment is unestablished. Our
      purpose was to conduct a study to assess the effect of a commercial tanning unit
      outfitted with nonprescription lamps on psoriasis. We conducted a 6-wk open study
      of 20 adult patients with stable psoriasis vulgaris. Clinical response was
      defined as a decrease in the Psoriasis Area Severity Index (PASI) or the Self
      Administered PASI (SAPASI) by > or = 10%. There were 16 men and 4 women who
      participated with a mean (+/-SD) age of 43.0 +/- 14.8 y. Initial and final health
      related quality of life information collected included the following instruments:
      the Brief Symptom Inventory (BSI), the Psoriasis-Related Stressor Scale (PRSS),
      and the Psoriasis Disability Scale (PDS). Side effects of tanning therapy were
      closely monitored. Fifteen subjects completed the entire 6-wk trial, and exit
      data on all subjects were used for analysis. The mean number of tanning sessions
      was 19 +/- 7.6 with a median of 19 and range of 3 to 29. Analysis of all 20
      enrolled subjects found that 16 (80%) showed clinical response as measured by
      PASI, whereas 17 (85%) showed SAPASI response. Initial and final PASI scores
      decreased (p = 0.0001) from 7.96 +/- 1.77 to 5.04 +/- 2.5, and SAPASI scores also
      decreased (p = 0.02) from 11.8 +/- 4.4 to 7.9 +/- 7.7. When controlled for age
      and sex, a dose-response relationship was demonstrated with the PASI and SAPASI
      (p < 0.02). Decreases in the mean BSI and PRSS scales were demonstrated (p <
      0.02), confirming the clinical significance of the reductions in disease severity
      scores. Episodes of mild burning occurred in 7 of 20 (35%) participants. Three
      subjects reported itching after one or two tanning sessions. This study showed
      that a tested commercial nonprescription tanning unit improved both psoriasis
      severity and health-related quality of life. Commercial tanning bed treatments
      may be a useful approach in patients unable to obtain office-based ultraviolet
      treatments.

PMID- 9242505
TI  - HLA-CW*0602 is a susceptibility factor in type I psoriasis, and evidence Ala-73
      is increased in male type I psoriatics.
AB  - We investigated the HLA-C locus of 87 unrelated patients with chronic plaque
      psoriasis by genotyping with sequence-specific amplification primers. The HLA
      Cw*0602 allele was significantly increased in male and female type I psoriatics
      but not significantly increased in either male or female type II psoriatics. The
      overall frequency of Ala-73 (present in Cw*04, Cw*0602, Cw*07, Cw*12, Cw*1503,
      and Cw*17) in psoriatics was 88.5% but the incidence of Ala-73 in our Caucasian
      controls was also high at 84.3%. Ala-73 was present in 97.2% of type I and 85.7%
      of type II male psoriatics (chi2 = 8.43, p = 0.001; chi2 = 0.01, p =
      nonsignificant, respectively), in contrast to 81.5% of type I and 80% of type II
      female psoriatics (nonsignificant). HLA-Cw*0602 appeared more discriminating in
      determining disease susceptibility in our population than Ala-73, in line with
      earlier serologic studies implicating HLA-Cw6. Thus, although the frequency of
      HLA-Cw*0602 decreased from 54.0% in type I to 29.2% in type II psoriatics, the
      overall frequency of Ala-73, present in 90.4% of type I and 83.3% of type II
      psoriatics, did not. (i) Thus this study confirms the strong association between
      psoriasis and HLA-Cw*0602 by using sequence-specific amplification primers. (ii)
      Results show that Ala-73 on HLA-C molecules is increased in frequency in
      psoriasis, but results observed show an association more subtle than previously
      thought, with HLA-Cw*0602 playing the major role. (iii) This report documents the
      differential association of HLA genes in male and female psoriatic patients. An
      interaction between gender and immunogenetics may influence susceptibility to
      psoriasis.

PMID- 9242504
TI  - Altered permeability and disordered cutaneous immunoregulatory function in mice
      with acute barrier disruption.
AB  - In vivo and in vitro T-cell-activating ability of murine epidermal cells (EC) was
      investigated in acutely barrier-disrupted skin by extraction of epidermal lipids
      with acetone or removal of corneocytes by tape stripping. Contact sensitivity
      (CS) to 2,4-dinitrofluorobenzene (DNFB) and picryl chloride (PCl) and contact
      photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) were significantly
      augmented when challenged or sensitized at sites treated with acetone 24 h
      before, compared with the intact skin. CS to DNFB was also enhanced by tape
      stripping, but not by water rubbing, suggesting that physical stress or a toxic
      effect of acetone was not responsible for the augmentation. Semi-quantification
      of TCSA-EC photoadducts showed markedly increased permeability of hapten in the
      epidermis 24 h after acetone treatment. Bioactive IL-1alpha was more pronounced
      in barrier-disrupted than in intact skin. Lymph node T cells from PCl-sensitized
      mice proliferated significantly more in a hapten-specific and co-stimulatory
      molecule-dependent manner in response to trinitrophenylated (TNP) EC from acetone
      treated skin than to those from untreated skin. Immunofluorescence staining of
      epidermal sheets and flow cytometric analysis of dispersed EC showed that
      subpopulations of Langerhans cells (LC) in acetone-rubbed or tape-stripped skin
      expressed major histocompatibility complex class II CD54 and CD86 molecules at
      levels higher than the rest of LC and LC from water-treated or untreated
      epidermis. Therefore, not only increased permeability of hapten through the
      epidermis but also altered immune functions of EC potentiate T-cell activation in
      acute barrier disruption. Such augmentation of immune reactivity may be critical
      to elimination of environmental noxious agents that penetrate easily into the
      barrier-disrupted epidermis.

PMID- 9242506
TI  - E2F as a regulator of keratinocyte proliferation: implications for skin tumor
      development.
AB  - E2F and DP family members are established regulators of the cell cycle. In this
      study, we examined their activity/expression during keratinocyte growth arrest.
      Treating human epidermal keratinocytes with the growth inhibitors TPA or IFN
      gamma or allowing the cells to reach confluence resulted in 90% inhibition of DNA
      synthesis, whereas a keratinocyte-derived squamous carcinoma cell line (SCC25)
      was resistant to growth inhibitors. Gel shift analysis of keratinocytes using an
      E2F response element indicated that growth arrest was associated with a decrease
      in all E2F binding complexes. This indicates that growth inhibition is not due to
      negative regulation by pocket proteins. Conversely, gel shift analysis of growth
      inhibitor-resistant SCC25 cells showed no decrease in E2F binding. If deregulated
      E2F expression/activity is involved in tumor development, then the deliberate
      deregulation of E2F activity may make keratinocytes resistant to growth
      inhibitors in much the same way as the SCC cells. The HPV16 E7 protein is known
      to activate E2F. Retroviral infection of keratinocytes with E7-expressing
      constructs resulted in growth inhibitor resistance, whereas infection with E6
      constructs did not. E2F is a heterodimeric complex consisting of E2F family
      members (1-5) and DP proteins (1-3). Examination of the expression levels for E2F
      genes and other genes associated with the cell cycle indicated that E2F1 was
      profoundly decreased in growth-arrested keratinocytes (90%), whereas E2F3, E2F5,
      and DP1 were not. E2F2 and E2F4 were increased in IFN-gamma-treated keratinocytes
      but not in TPA-treated or confluent keratinocytes. In contrast, SCC25 cells did
      not undergo growth arrest and did not downregulate E2F1 mRNA expression in
      response to growth inhibitors. Our results indicate that E2F DNA binding and in
      particular E2F1 mRNA expression are associated with keratinocyte proliferation.
      Our results with the SCC25 cells and the E7-infected cells are consistent with
      the proposition that deregulated E2F expression/activity (in particular E2F1) may
      be involved in the unregulated proliferation of skin tumor cells.

PMID- 9242507
TI  - Identification of a cell surface protein with a role in stimulating human
      keratinocyte proliferation, expressed during development and carcinogenesis.
AB  - In an attempt to define cell surface molecules with an important role in the
      development of squamous cell carcinomas (SCCs), we generated monoclonal
      antibodies (MoAbs) to a human keratinocyte cell line (FEP18-11-T1) capable of
      giving rise to SCCs in nude mice. MoAb 10G7 was selected for further study
      because it bound to a cell surface component preferentially expressed by this
      cell line as compared with normal human foreskin keratinocytes. This MoAb
      recognizes a cell surface protein (10G7 antigen) that is not detectable on normal
      keratinocytes in the foreskin in vivo, but whose expression is induced when the
      keratinocytes are dissociated from this tissue and placed in culture.
      Interestingly, the 10G7 antigen is downregulated upon keratinocyte
      differentiation in vitro. Consistent with its expression in hyper-proliferative
      epithelia in vitro, 10G7 antigen exhibited a classic oncofetal pattern of
      expression in vivo. Thus, although no reactivity was obtained with MoAb 10G7 in
      the epithelia of normal foreskin or cervical tissue, strong reactivity was
      detected in epithelia from genital lesions ranging from benign warts to invasive
      SCCs. Epidermis from developing fetal tissue also exhibited strong reactivity
      with MoAb 10G7. We have been able to demonstrate that this MoAb is capable of
      stimulating FEP18-11-T1 keratinocyte proliferation in vitro in a concentration
      dependent manner in the absence of growth factors, suggesting that the 10G7
      antigen may play an important role in regulating cellular proliferation during
      development and in carcinogenesis in epithelial tissues.

PMID- 9242508
TI  - The extracellular domain of BPAG2 localizes to anchoring filaments and its
      carboxyl terminus extends to the lamina densa of normal human epidermal basement
      membrane.
AB  - Bullous pemphigoid antigen 2 (BPAG2) is a 180 kDa type II transmembrane protein
      associated with hemidesmosomes (HDs) in basal keratinocytes. To better understand
      how BPAG2 promotes keratinocyte adhesion to epidermal basement membrane (BM),
      purified IgG against a baculovirus-encoded recombinant was used to localize its
      carboxyl terminus in human skin by immunogold electron microscopy (IEM). A 2.1-kb
      BPAG2 cDNA encoding the distal extracellular domain and carboxyl terminus of
      BPAG2 was used in a baculovirus expression system to create virus that produced a
      70-kDa recombinant form of BPAG2 (BV4). BV4 was purified, characterized, and used
      to raise high-titer specific rabbit IgG. Purified anti-BV4 IgG bound the
      epidermal side of 1 M NaCl split skin and bound only BPAG2 on immunoblots
      containing extracts of human keratinocytes. In IEM studies of pre- and post
      embedded skin, the distal ectodomain of BPAG2 localized beneath HDs in basal
      keratinocytes; there was no evidence of BPAG2 beneath melanocytes. Anti-BV4 IgG
      extensively bound anchoring filaments on the epidermal side of 1 M NaCl split
      skin; this staining extended along anchoring filaments to their ends. In post
      embedded skin, the carboxyl terminus of BPAG2 was localized within the lamina
      densa, 41 nm (mean of 400 determinations) beneath plasma membranes of basal
      keratinocytes. BPAG2 thus extends from the intracellular HD plaque of basal
      keratinocytes to the lamina densa of human epidermal BM.

PMID- 9242509
TI  - Mutational analysis of copper binding by human tyrosinase.
AB  - Tyrosinase (EC 1.14.18.1) is a copper-containing enzyme that catalyzes several
      reactions in the biosynthesis of melanin pigments and is deficient in patients
      with type I oculocutaneous albinism (OCA1). Tyrosinase is thought to bind two
      copper ions, one at each of two conserved sequence motifs, termed CuA and CuB,
      but to date this has been directly proved only for the Neurospora and mushroom
      enzyme. Here, we demonstrate that mammalian tyrosinase directly binds copper, and
      that the CuA and CuB sites are both required for copper binding and for catalytic
      activity. We show that in human tyrosinase, copper binding by the CuB site is
      most likely coordinated by residues His363, His367, and His389, and that copper
      binding may be cooperative, with copper binding at one site facilitating copper
      binding by the other site. Furthermore, correct folding of the tyrosinase
      polypeptide appears to be necessary for copper binding, and a number of human
      OCA1 mutations disrupt copper binding and thus catalytic function of tyrosinase.

PMID- 9242510
TI  - CD44 substituted with heparan sulfate and endo-beta-galactosidase-sensitive
      oligosaccharides: a major proteoglycan in adult human epidermis.
AB  - CD44 is a group of cell surface glycoproteins that is generated from a single
      gene by mRNA splice variation. Its functions in matrix adhesion and tumor
      invasion are strongly influenced by glycosylation. We studied the glycosylated
      tissue forms of CD44 from extracts of normal adult human epidermis by using
      western blotting and immunoprecipitation from short-term skin organ cultures. An
      antibody for CD44 (Hermes 3) precipitated 7-17% of all 35SO4-labeled
      proteoglycans (PGs) synthesized in epidermis. Immunoprecipitates digested with
      heparitinase lost 40-68% of incorporated 35SO4 and 24-40% of [3H]glucosamine,
      indicating that heparan sulfate was the predominant glycosaminoglycan in
      epidermal CD44. Chondroitinase ABC released 10-25% and 6-12% of 35SO4 and
      [3H]glucosamine, respectively. Less than 5% of both isotopes were susceptible to
      keratanase. Five to 33% of 35SO4 and 26-37% of [3H]glucosamine, however, was
      released by endo-beta-galactosidase, implying marked substitution by
      oligosaccharides with N-acetyllactosamine repeats. Heparitinase pretreatment
      retarded, whereas endo-beta-galactosidase enhanced the mobility of the > or = 180
      kDa polydisperse CD44 on agarose gel electrophoresis. On SDS-polyacrylamide gel
      electrophoresis, however, western blotting and fluorographs of 35SO4-labeled
      immunoprecipitates showed the main CD44 isoform at > or = 250 kDa and a shift to
      180-200 kDa after heparitinase treatment. Keratanase, keratanase II, and
      chondroitinase ABC had minor effects. A less abundant form of CD44, with a core
      of 100 kDa, partly substituted with chondroitinase ABC- and endo-beta
      galactosidase-sensitive chains, was also present. Therefore, the large heparan
      sulfate-substituted CD44 forms a significant part of all proteoglycans in normal
      human epidermis. Both the large and the 100-kDa variant of epidermal CD44 contain
      endo-beta-galactosidase-sensitive oligosaccharides not previously noted in other
      cells or tissues.

PMID- 9242511
TI  - Developmentally programmed expression of hyaluronan in human skin and its
      appendages.
AB  - The expression of hyaluronan (HA) in fetal human skin was studied by using a
      biotinylated HA-binding probe. The uniform expression of HA in primitive skin was
      changed after the 9th week, when differentiation of the basement membrane zone
      increased HA in the subepidermal mesenchyme. Maturation of the papillary dermis
      at the 12-20th weeks led to the thickening of this HA-enriched zone; the
      underlying reticular layer was less intensely stained. In epidermis the number of
      cell layers rapidly increased after the 9th week. At first all epidermal layers
      were HA-positive. A complete loss of HA from the upper intermediate cells on the
      18th week preceded the formation of mature granular and cornified layers.
      Peridermal cells remained HA-positive even when the underlying stratum corneum
      turned negative. The tightly apposed basal epithelial cells, the first stage of
      hair follicle and eccrine sweat gland formation, became almost completely
      depleted of HA. With advancing bulb development HA returned in the epithelial
      compartment, until maturation of the hair follicles restricted its expression to
      the outer root sheath and hair matrix. Maturation of the sebaceous glands led to
      the expression of HA pericellularly in the germinative cells and intracellularly
      in the mature sebocytes. Marked changes thus occur in the distribution of HA
      during fetal skin development; the primitive tissues exhibited a uniform
      widespread expression of HA, and maturing tissues showed distinct locally
      regulated patterns. The loss of epithelial HA in the hair follicle anlagen and
      upper intermediate cells turned out to be early differentiation markers.

PMID- 9242512
TI  - Human collagenase-3 is expressed in malignant squamous epithelium of the skin.
AB  - Co-expression of several members of the matrix metalloproteinase (MMP) family is
      a characteristic of human carcinomas. To investigate the role of the recently
      cloned collagenase-3 (MMP-13) in epidermal tumors, we studied samples
      representing malignant (basal and squamous cell carcinoma, Paget's disease), pre
      malignant (Bowen's disease, solar keratosis), and benign (keratoacanthoma,
      seborrheic keratosis, linear epidermal nevus) tumors. Basal cell carcinomas
      expressed collagenase-3 mRNA in focal areas of keratinized cells, the squamous
      differentiation of which was confirmed by positive immunostaining for involucrin.
      Apoptosis was observed in central parts of these foci. In squamous cell
      carcinomas, collagenase-3 expression was detected at the epithelial tumor front
      and less frequently in the surrounding stromal cells. Collagenase-3 mRNA co
      localized with immunostaining for laminin-5, an adhesion molecule suggested to
      participate in the migration of tumor cells. The pre-malignant and benign tumors
      were mostly negative for collagenase-3. Stromelysin-1, a potential activator of
      latent collagenases, was frequently expressed by stromal cells surrounding the
      malignant tumors, and the two MMPs occasionally co-localized in keratotic foci.
      Our results demonstrate that in basal cell carcinomas, expression of collagenase
      3 is associated with terminal differentiation of epithelial cells. Furthermore,
      the gene is activated during skin carcinogenesis, and we suggest a role for
      collagenase-3 in degradation of the extracellular matrix associated with
      malignant epithelial growth.

PMID- 9242513
TI  - Predominance of the recurrent mutation R635X in the LAMB3 gene in European
      patients with Herlitz junctional epidermolysis bullosa has implications for
      mutation detection strategy.
AB  - Junctional forms of epidermolysis bullosa (JEB) are characterized by tissue
      separation at the level of the lamina lucida. We have recently disclosed specific
      mutations in the LAMA3, LAMB3, and LAMC2 genes encoding the subunit polypeptides
      of the anchoring filament protein laminin 5 in 66 families with different
      variants of JEB. Examination of the JEB mutation database revealed recurrence of
      a particular C-->T substitution at nucleotide position 1903 (exon 14) of LAMB3,
      resulting in the mutation R635X. The inheritance of this nonsense mutation was
      noted on different genetic backgrounds, suggesting that R635X is a hotspot
      mutation. In this study, we have performed mutation evaluation in a European
      cohort of 14 families with the lethal, Herlitz type of JEB (H-JEB). The families
      were first screened for the presence of the R635X mutation by restriction enzyme
      digestion of the PCR product corresponding to exon 14. Four of the probands were
      found to be homozygous and six were heterozygous for R635X. The remaining alleles
      were subjected to mutation screening by PCR amplification of individual exons of
      LAMB3 and LAMC2, followed by heteroduplex analysis and nucleotide sequencing. In
      three families (six alleles), mutations in LAMC2 were disclosed. In the remaining
      eight alleles, additional pathogenetic LAMB3 mutations were found. None of the
      patients had LAMA3 mutation. Thus, LAMB3 mutations accounted for 22 of 28 JEB
      alleles (79%), and a total of 14 of 22 LAMB3 alleles (64%) harbored the R635X
      mutation, signifying its prevalence as a predominant genetic lesion underlying H
      JEB in this European cohort of patients. This recurrent mutation will facilitate
      screening of additional JEB patients for the purpose of prenatal testing of
      fetuses at risk for recurrence.

PMID- 9242515
TI  - A novel point mutation in the steroid sulfatase gene in X-linked ichthyosis.
AB  - We analyzed the steroid sulfatase (STS) gene in nine Japanese patients with X
      linked ichthyosis (XLI) by a polymerase chain reaction technique and subsequent
      DNA sequencing. Eight of nine patients showed complete deletion of the STS gene.
      In a patient of XLI exhibiting a normal amplifying pattern with predicted sizes
      of the STS gene, a novel mutation was found resulting in the appearance of a stop
      codon in exon 7 of the STS gene. This suggests that exon 7 or an area in its
      downstream region is important for STS activity.

PMID- 9242514
TI  - p53 mutation in squamous cell carcinomas from psoriasis patients treated with
      psoralen + UVA (PUVA).
AB  - Individuals suffering from psoriasis are treated with a combination of psoralen
      and UVA radiation, commonly referred to as "PUVA" therapy. Epidemiologic studies
      have shown that PUVA therapy is a risk factor for skin cancer in psoriasis
      patients. Although PUVA treatment induces skin cancer in laboratory animals, it
      is unknown whether the increased incidence of skin cancer reported in PUVA
      treated psoriasis patients is due to the carcinogenic effects of PUVA or due to
      other factors such as UVB. Because UV and PUVA induce different types of DNA
      damage resulting in unique types of p53 mutation, we investigated whether skin
      cancers from PUVA-treated psoriasis patients have PUVA-type or UV-type p53
      mutations. Analysis of 17 squamous cell carcinomas (SCCs) from Austrian PUVA
      treated patients revealed a total of 25 p53 mutations in 11 SCCs. A majority of
      p53 mutations occurred at 5'TpG sites. Although previous studies have shown that
      5'TpA sites are the primary targets for PUVA mutagenesis, substitutions at 5'TpG
      sites are also quite common. Interestingly, a sizable portion of p53 mutations
      detected were C-->T or CC-->TT transitions, characteristic of UV-induced
      mutations. Because some psoriasis patients had substantial exposure to UVB before
      PUVA therapy and because the light sources used in PUVA therapy contained small
      but significant wavelengths in the UVB region, it is possible that the C-->T and
      CC-->TT transitions detected in SCCs from PUVA-treated patients were induced by
      UVB. Nonetheless, our results indicate that both PUVA and UVB may play a role in
      the development of skin cancer in Austrian psoriasis patients who undergo PUVA
      therapy.

PMID- 9242516
TI  - Recurrent mutations in the type VII collagen gene (COL7A1) in patients with
      recessive dystrophic epidermolysis bullosa.
AB  - Mutations in the type VII collagen gene (COL7A1) are known to underlie different
      forms of the inherited blistering skin disease dystrophic epidermolysis bullosa
      (DEB). Most COL7A1 mutations are unique to individual families, and therefore it
      is usually necessary to screen all 118 exons of the gene to determine the
      molecular pathology in a patient with DEB. This study aimed to identify any
      recurrent mutations in COL7A1 that might be applicable to mutation-detection
      strategies in these patients. Mutational analysis was undertaken in 23 British
      patients with autosomal recessive DEB using PCR amplification of genomic DNA
      followed by heteroduplex analysis, nucleotide sequencing, and restriction site
      analysis. Two recurrent mutations were identified: R578X (6 of 46 alleles) and
      7786delG (7 of 46 alleles). Haplotype analysis revealed that the mutations
      existed on similar allelic backgrounds in different patients, consistent with
      propagation of common British ancestral haplotypes, although R578X and 7786delG
      also have been described in DEB patients from other ethnic backgrounds. Given the
      high relative frequency of these two COL7A1 mutations, British patients with
      recessive DEB should be screened initially for these nucleotide changes by PCR
      amplification of genomic DNA and restriction analysis before more exhaustive
      screening of COL7A1.

PMID- 9242517
TI  - "Normal" development of Vgamma3 dendritic epidermal T cells in CD45-deficient
      mice?

PMID- 9242518
TI  - Allogeneic blood stem cell transplantation: considerations for donors.
AB  - Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells
      (PBSCs) is now being increasingly performed, but safety considerations for
      hematologically normal PBSC donors have not been fully addressed. Progenitors are
      generally mobilized for collection from normal donors using recombinant human
      granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety
      profile of rhG-CSF seems acceptable, experience remains limited and its optimal
      dose and schedule have not been defined. Minimal data exist regarding long-term
      safety of rhG-CSF, primarily derived from experience in patients with chronic
      neutropenia or cancer. An "ad hoc" workshop was recently convened among a group
      of investigators actively involved in the field of allogeneic stem cell
      transplantation to discuss the safety issues pertaining to normal PBSC donors.
      There was agreement on the following points: (1) On the basis of available data,
      it appears that rhG-CSF treatment and PBSC collection have an acceptable short
      term safety profile in normal donors. However, the need for continued safety
      monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a
      consistent dose-response relationship with the mobilization (and collection) of
      CD34+ progenitor cells, and this dose is acceptable for routine clinical use.
      Whether higher doses are superior (or cost effective) remains to be determined,
      and they may produce more severe side effects. The potential risks of marked
      leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L)
      have been a concern, and rhG-CSF dose reduction is performed by many centers to
      maintain leukocyte counts below this level. (3) Transient post donation
      cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are
      at least partly related to the leukapheresis procedure. These are generally
      asymptomatic and self-limited; follow-up blood counts are not necessarily
      required. Reinfusion of autologous platelet-rich plasma should be considered for
      donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x
      10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors
      of apheresis platelets, with the exception that pediatric donors may also be
      considered. Any deviation from these criteria should have supporting
      documentation. There is insufficient information at this time to clearly
      establish definite contraindications for PBSC collection in a hematologically
      normal donor. Potential contraindications include the presence of inflammatory,
      autoimmune, or rheumatologic disorders, as well as atherosclerotic or
      cerebrovascular disease. (5) The creation of an International PBSC Donor Registry
      is desirable to facilitate monitoring the long-term effects of the procedure.
      Individual institutions or donor centers are encouraged to establish their own
      PBSC donor follow-up system, preferably with a standardized approach to data
      collection.

PMID- 9242519
TI  - Chemokines.

PMID- 9242520
TI  - Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3.
AB  - Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as
      being induced by a variety of environmental stresses such as osmotic shock,
      ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor
      necrosis factor-alpha and interleukin-1 (IL-1). We found that the hematopoietic
      cytokines erythropoietin (Epo) and IL-3, which regulate growth and
      differentiation of erythroids and hematopoietic progenitors, respectively, also
      activate a p38 cascade. Immunoblot analyses and in vitro kinase assay clearly
      showed that Epo and IL-3 rapidly and transiently phosphorylated and activated p38
      in Epo- or IL-3-dependent mouse hematopoietic progenitor cells. p38 can generally
      be activated by the upstream kinase MKK3 or MKK6. However, in vitro kinase assays
      in the immunoprecipitates with anti-MKK6 antibody and anti-phosphorylated
      MKK3/MKK6 antibody showed that activation of neither MKK3 nor MKK6 was detected
      after Epo or IL-3 stimulation, while osmotic shock clearly induced activation of
      both MKK3/MKK6 and p38. Together with previous observations, these results
      suggest that both p38 and JNK cascades play an important role not only in stress
      and proinflammatory cytokine responses but also in hematopoietic cytokine
      actions.

PMID- 9242521
TI  - Comparison of apoptosis in wild-type and Fas-resistant cells: chemotherapy
      induced apoptosis is not dependent on Fas/Fas ligand interactions.
AB  - The Fas/Fas ligand (FasL) pathway is widely involved in apoptotic cell death in
      lymphoid and nonlymphoid cells. It has recently been postulated that many
      chemotherapeutic agents also induce cell death by activating the Fas/FasL
      pathway. In the present study we compared apoptotic pathways induced by anti-Fas
      or chemotherapeutic agents in the Jurkat human T-cell leukemia line.
      Immunoblotting showed that treatment of wild-type Jurkat cells with anti-Fas or
      the topoisomerase II-directed agent etoposide resulted in proteolytic cleavage of
      precursors for the cysteine-dependent aspartate-directed proteases caspase-3 and
      caspase-7 and degradation of the caspase substrates poly(ADP-ribose) polymerase
      (PARP) and lamin B1. Likewise, affinity labeling with N-(N(alpha)
      benzyloxycarbonylglutamyl-N(epsilon)-biotinyllysyl+ ++)aspartic acid [(2,6
      dimethyl-benzoyl)oxy]methyl ketone [Z-EK(bio)D-amok] labeled the same five active
      caspase species after each treatment, suggesting that the same downstream
      apoptotic pathways have been activated by anti-Fas and etoposide. Treatment with
      ZB4, an antibody that inhibits Fas-mediated cell death, failed to block etoposide
      induced apoptosis, raising the possibility that etoposide does not initiate
      apoptosis through Fas/FasL interactions. To further explore the relationship
      between Fas- and chemotherapy-induced apoptosis, Fas-resistant Jurkat cells were
      treated with various chemotherapeutic agents. Multiple independently derived Fas
      resistant Jurkat lines underwent apoptosis that was indistinguishable from that
      of the Fas-sensitive parental cells after treatment with etoposide, doxorubicin,
      topotecan, cisplatin, methotrexate, staurosporine, or gamma-irradiation. These
      results indicate that antineoplastic treatments induce apoptosis through a Fas
      independent pathway even though Fas- and chemotherapy-induced pathways converge
      on common downstream apoptotic effector molecules.

PMID- 9242522
TI  - Tissue factor pathway inhibitor gene disruption produces intrauterine lethality
      in mice.
AB  - Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type proteinase
      inhibitor that directly inhibits factor Xa and, in a factor Xa-dependent fashion,
      produces feedback inhibition of the factor VIIa/TF catalytic complex responsible
      for the initiation of coagulation. To further define the physiologic role of
      TFPI, gene-targeting techniques were used to disrupt exon 4 of the TFPI gene in
      mice. This exon encodes Kunitz domain-1 of TFPI, which is required for factor
      VIIa/TF inhibition. In mice heterozygous for TFPI gene-disruption, TFPI(K1)(+/-),
      an altered form of TFPI lacking Kunitz domain-1, circulates in plasma at a
      concentration approximately 40% that of wild-type TFPI. TFPI(K1)(+/-) animals
      have plasma TFPI activity approximately 50% that of wild-type mice, based on a
      functional assay that measures factor VIIa/TF inhibition, and have a normal
      phenotype. Sixty percent of TFPI(K1)(-/-) mice die between embryonic days E9.5
      and E11.5 with signs of yolk sac hemorrhage. The extent of structural
      abnormalities within the yolk sac vascular system appears to mirror the condition
      of the embryo, suggesting that the embryonic and extra-embryonic tissues are both
      responding to same insult, presumably circulatory insufficiency. Organogenesis is
      normal in TFPI(K1) null animals that progress beyond E11.5, but hemorrhage,
      particularly in the central nervous system and tail, is evident during later
      gestation and none of the TFPI(K1)(-/-) mice survive to the neonatal period. The
      presence of immunoreactive fibrin(ogen) in the liver and intravascular thrombi is
      consistent with the notion that unregulated factor VIIa/TF action and a
      consequent consumptive coagulopathy underlies the bleeding diathesis in these
      older embryos. Human TFPI-deficient embryos may suffer a similar fate because an
      individual with TFPI deficiency has not been identified.

PMID- 9242523
TI  - Recombinant retroviruses pseudotyped with the vesicular stomatitis virus G
      glycoprotein mediate both stable gene transfer and pseudotransduction in human
      peripheral blood lymphocytes.
AB  - It is essential for the study of T-cell function and the improvement of adoptive
      cell therapies to efficiently generate large populations of human primary T cells
      that reliably express foreign genes. This goal is achieved by using recombinant
      retroviruses pseudotyped with either the gibbon ape leukemia virus (GaLV)
      envelope or the vesicular stomatitis virus G (VSV-G) glycoprotein. We show here
      that both retroviral particles mediate stable gene transfer in CD4+ and in CD8+
      peripheral blood lymphocytes cultured under optimized conditions. However, VSV-G
      pseudotyped virions may cause transduction artifacts that must be carefully
      excluded. The VSV-G virions require 10- to 100-fold higher concentrations of
      infectious particles to achieve levels of gene transfer comparable to GaLV
      virions. Nonetheless, the physical stability of VSV-G-coated particles enables
      the concentration of viral stocks to 10(9) infectious particles per milliliter or
      more.

PMID- 9242524
TI  - Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous
      conjunctivitis.
AB  - Ligneous conjunctivitis is a rare and unusual form of chronic pseudomembranous
      conjunctivitis that usually starts in early infancy. The disease may be
      associated with pseudomembranous lesions of other mucous membranes in the mouth,
      nasopharynx, trachea, and female genital tract. We examined two unrelated Turkish
      girls both suffering from ligneous conjunctivitis and occlusive hydrocephalus.
      Both children exhibited a severe plasminogen deficiency. Genomic DNA from both
      patients as well as from clinically healthy family members were screened for
      mutations in the plasminogen gene by polymerase chain reaction, single-strand
      conformation polymorphism (SSCP) analysis, and DNA sequencing. In the first girl
      with ligneous conjunctivitis a homozygous G-->A point mutation was identified in
      plasminogen exon 7 at position 780 leading to an amino acid exchange (Arg216-
      >His). Her healthy sister and her healthy parents were heterozygous for this
      mutation. The second patient revealed a homozygous G-->A point mutation in
      plasminogen exon 15 at position 1924 which leads to a stop-codon (Trp597-->Stop).
      The healthy parents were shown to be heterozygous for this mutation. In addition,
      the father's second allele revealed another mutation in the same codon (Trp597-
      >Cys) (compound heterozygosity). In conclusion, certain homozygous mutations in
      the plasminogen gene may cause ligneous conjunctivitis.

PMID- 9242525
TI  - Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia
      relapsed from complete remission induced by all-trans retinoic acid.
AB  - Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major
      advance and become the first choice drug in the treatment of acute promyelocytic
      leukemia (APL). However, patients who relapse from ATRA-induced complete
      remission (CR) have difficulty in obtaining a second CR with a second course of
      ATRA therapy alone. We tested the efficacy of a new synthetic retinoid, Am80, in
      APL that had relapsed from CR induced by ATRA in a prospective multicenter study.
      Am80 is approximately 10 times more potent than ATRA as an in vitro
      differentiation inducer, is more stable to light, heat, and oxidation than ATRA,
      has a low affinity for cellular retinoic acid binding protein, and does not bind
      to retinoic acid receptor-gamma. Patients received Am80, 6 mg/m2, orally alone
      daily until CR. Of 24 evaluable patients, 14 (58%) achieved CR. The interval from
      the last ATRA therapy was not different between CR and failure cases. The
      clinical response was well correlated with the in vitro response to Am80 in
      patients examined. Adverse events included 1 retinoic acid syndrome, 1
      hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15
      hypercholesterolemia, but generally milder than those of ATRA, which all patients
      had received previously. Am80 is effective in APL relapsed from ATRA-induced CR
      and deserves further trials, especially in combination with chemotherapy.

PMID- 9242527
TI  - Kinetics of central nervous system microglial and macrophage engraftment:
      analysis using a transgenic bone marrow transplantation model.
AB  - To determine the kinetics of tissue macrophage and microglial engraftment after
      bone marrow (BM) transplantation, we have developed a model using the ROSA 26
      mouse. Transplanted ROSA 26 cells can be precisely identified in recipient
      animals because they constitutively express beta-galactosidase (beta-gal) and
      neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from
      ROSA 26 donors and their tissues (spleen, marrow, brain, liver, and lung)
      examined at various time points to determine the kinetics of engraftment. Frozen
      sections from transplanted animals were stained histochemically for beta-gal to
      identify donor cells. At 1, 2, 6, and 12 months posttransplantation, 98% to 100%
      of granulocyte-macrophage colonies were of donor (ROSA 26) origin determined by
      beta-gal staining and by neomycin resistance. Splenic monocytes/macrophages were
      89% donor origin by 1 month confirming quick and complete engraftment of
      hematopoietic tissues. At this time, only rare ROSA 26 tissue macrophages or
      microglia were observed. Alveolar macrophage engraftment was evident by 2 months
      and had increased to 61% of total tissue macrophages at 1 year
      posttransplantation. The kinetics of liver Kupffer cell engraftment were similar
      to those seen in the lung. However, donor microglial engraftment remained only
      23% of total microglia at 6 months and increased to only 30% by 1 year. Also,
      donor microglia were predominantly seen at perivascular and leptomeningeal, and
      not parenchymal, sites. The data show that microglia derive from BM precursors
      but turn over at a significantly slower rate than other tissue macrophages. No
      clinical or histological graft-versus-host disease was observed in the recipients
      of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of
      lysosomal storage diseases. Because individual donor cells can be identified in
      situ, the ROSA 26 model should have many applications in transplantation biology
      including studies of homing and differentiation.

PMID- 9242526
TI  - Inactivation of the Fanconi anemia group C gene augments interferon-gamma-induced
      apoptotic responses in hematopoietic cells.
AB  - Hematopoietic progenitor cells (HPC) from mice nullizygous at the Fanconi anemia
      (FA) group C locus (FAC -/-) are hypersensitive to the mitotic inhibitory effects
      of interferon (IFN-gamma). We tested the hypothesis that HPC from the bone marrow
      of Fanconi group C children are similarly hypersensitive and that the fas pathway
      is involved in affecting programmed cell death in response to low doses of IFN
      gamma. In normal human and murine HPC, IFN-gamma primed the fas pathway and
      induced both fas and interferon response factor-1 (IRF-1) gene expression. These
      IFN-gamma-induced apoptotic responses in HPC from the marrow of a child with FA
      of the C group (FA-C) and in FAC -/- mice occurred at significantly lower IFN
      doses (by an order of magnitude) than did the apoptotic responses of normal HPC.
      Treatment of FA-C CD34+ cells with low doses of recombinant IFN-gamma, inhibited
      growth of colony forming unit granulocyte-macrophage and burst-forming unit
      erythroid, while treatment with blocking antibodies to fas augmented clonal
      growth and abrogated the clonal inhibitory effect of IFN-gamma. Transfer of the
      normal FAC gene into FA-C B-cell lines prevented mitomycin C-induced apoptosis,
      but did not suppress fas expression or inhibit the primed fas pathway. However,
      the kinetics of Stat1-phosphate decay in IFN-gamma-treated cells was prolonged in
      mutant cells and was normalized by transduction of the normal FAC gene.
      Therefore, the normal FAC protein serves, in part, to modulate IFN-gamma signals.
      HPC bearing inactivating mutations of FAC fail to normally modulate IFN-gamma
      signals and, as a result, undergo apoptosis executed through the fas pathway.

PMID- 9242528
TI  - Phlebotomy to reduce iron overload in patients cured of thalassemia by bone
      marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of
      Transplanted Thalassemia Patients.
AB  - In thalassemia after successful bone marrow transplantation (BMT), iron overload
      remains an important cause of morbidity. After BMT, patients have normal
      erythropoiesis capable of producing a hyperplastic response to phlebotomy so that
      this procedure can be contemplated as a method of mobilizing iron from overloaded
      tissues. A phlebotomy program (6 mL/kg blood withdrawal at 14-day intervals) was
      proposed to 48 patients with prolonged follow-up (range, 2 to 7 years) after BMT.
      Seven patients were not submitted to the program (five because of refusal and two
      because of reversible side effects). The remaining 41 patients (mean age, 16 +/-
      2.9 years) were treated for a mean period of 35 +/- 18 months. All were evaluated
      before and after 3 +/- 0.6 years of follow-up. Values are expressed as mean +/-
      standard deviation (SD) or as median with a range (25 to 75 percentile). Serum
      ferritin decreased from 2,587 (2,129 to 4,817) to 417 (210 to 982) microg/L (P <
      .0001), total transferrin increased from 2.34 +/- 0.37 to 2.7 +/- 0.58 g/L (P =
      .0001), transferrin saturation decreased from 90% +/- 14% to 50% +/- 29% (P <
      .0001). Liver iron concentration evaluated on liver biopsy specimens decreased
      from 20.8 (15.5 to 28.1) to 4.2 (1.6 to 14.6) mg/g dry weight (P < .0001).
      Aspartate transaminase decreased from 2.7 +/- 2 to 1.1 +/- 0.6 (P < .0001) and
      alanine transaminase from 5.2 +/- 3.4 to 1.7 +/- 1.2 (P < .0001) times the upper
      level of normality. The Knodell score for liver histological activity decreased
      from 6.9 +/- 3 to 4.9 +/- 2.8 (P < .0001). These data indicate that phlebotomy is
      safe, efficient, and widely applicable to ex-thalassemics after BMT.

PMID- 9242529
TI  - Fusarium, a significant emerging pathogen in patients with hematologic
      malignancy: ten years' experience at a cancer center and implications for
      management.
AB  - Despite increasing reports of life-threatening Fusarium infections, little is
      known about its pathogenesis and management. To evaluate the epidemiology,
      clinicopathologic features, and outcome of invasive fusariosis in patients with
      hematologic cancer, we conducted a retrospective study of invasive fusarial
      infections in patients with hematologic malignancy treated at a referral cancer
      center over a 10-year period (1986 to 1995), as well as a literature review.
      Forty patients with disseminated and three patients with invasive lung infection
      were included in the analysis. All patients were immunocompromised. The infection
      occurred in three patients postengraftment following bone marrow transplantation.
      All patients were diagnosed antemortem. Thirteen patients responded to therapy,
      but the infection relapsed in two of them. Response was associated with
      granulocyte transfusions, amphotericin B lipid formulations (four patients each),
      and an investigational triazole (two patients). Resolution of infection was only
      seen in patients who ultimately recovered from myelosuppression. Portal of entry
      was the skin (33%), the sinopulmonary tree (30%), and unknown (37%). Fusarium
      causes serious morbidity and mortality, and may mimic aspergillosis. The
      infection seems to respond to newer therapeutic approaches, but only in patients
      with ultimate recovery from myelosuppression, and it may relapse if neutropenia
      recurs.

PMID- 9242530
TI  - Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal
      complication in children with acquired aplastic anemia.
AB  - The improved outcome of acquired aplastic anemia (AA) has revealed later
      complications, such as myelodysplastic syndrome (MDS) and acute myelogenous
      leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA.
      Eleven of 50 children treated with cyclosporin (CSA) and recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) developed MDS/AML; 8 of these
      were within 36 months of the diagnosis of AA, much earlier than previous reports.
      Six of the 11 children received rhG-CSF exceeding 10 microg/kg/d, and 9 received
      rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of
      MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no
      development of MDS/AML among 41 children treated with either CSA or rhG-CSF or
      among 48 children who underwent bone marrow transplantation. A well-controlled
      clinical trial is warranted to determine whether therapeutic modalities affect
      the development of MDS/AML in children with severe acquired AA.

PMID- 9242531
TI  - Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by
      combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano
      Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia
      ed Oncologia Pediatrica Cooperative Groups.
AB  - Two hundred fifty-three patients with newly diagnosed acute promyelocytic
      leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial
      during the period July 1993 to February 1996. As a mandatory prerequisite for
      eligibility, all patients had genetic evidence of the specific t(15;17) lesion in
      their leukemic cells confirmed by karyotyping or by reverse transcription
      polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter
      available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9).
      Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d
      until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on
      days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation.
      Hematologic and molecular response by RT-PCR was assessed after induction and
      after consolidation. At the time of analysis, 240 of the 253 eligible patients
      were evaluable for induction. Of these, 11 (5%) died of early complications and
      229 (95%) achieved hematologic remission. No cases of resistant leukemia were
      observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR
      negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were
      evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR
      negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range,
      0 to 33), the estimated actuarial event-free survival for the whole series of 253
      eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years,
      respectively. This study indicates that the AIDA protocol is a well-tolerated
      regimen that induces molecular remission in almost all patients with PML/RAR
      alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate
      can be obtained with this treatment.

PMID- 9242532
TI  - Isolation and identification of hematopoietic stem cell-stimulating substances
      from Kampo (Japanese herbal) medicine, Juzen-taiho-to.
AB  - We have previously found that TJ-48 has the capacity to accelerate recovery from
      hematopoietic injury induced by radiation and the anti-cancer drug mitomycin C
      (MMC). The effects are found to be due to its stimulation of spleen colony
      forming unit (CFU-S) counts on day 14. In the present study, we attempt to
      isolate and purify the active components in TJ-48 extracts using a new in vitro
      hematopoietic stem cell (HSC) assay method. n-Hexane extract from TJ-48 shows a
      significant stimulatory activity. The extract is further fractionated by silica
      gel chromatography and HPLC in order to identify its active components. 1H-NMR
      and GC-EI-MS indicate that the active fraction is composed of free fatty acids
      (oleic acid and linolenic acid). When 27 kinds of free fatty acids (commercially
      available) are tested using the HSC proliferating assay, oleic acid, elaidic
      acid, and linolenic acid are found to have potent activity. The administration of
      oleic acid to MMC-treated mice enhances CFU-S counts on days 8 and 14 to twice
      the control group. These findings strongly suggest that fatty acids contained in
      TJ-48 actively promote the proliferation of HSCs. Although many mechanisms seem
      to be involved in the stimulation of HSC proliferation, we speculate that at
      least one of the signals is mediated by stromal cells, rather than any direct
      interaction with the HSCs.

PMID- 9242533
TI  - Hematopoietic and lymphopoietic responses in human granulocyte-macrophage colony
      stimulating factor (GM-CSF) receptor transgenic mice injected with human GM-CSF.
AB  - Using a clonal assay of bone marrow (BM) cells from transgenic mice (Tg-mice)
      expressing the human granulocyte-macrophage colony-stimulating factor receptor
      (hGM-CSFR), we found in earlier studies that hGM-CSF alone supported the
      development not only of granulocyte-macrophage colonies, but also of
      erythrocytes, megakaryocytes, mast cells, blast cells, and mixed hematopoietic
      colonies. In this report, we evaluated the in vivo effects of hGM-CSF on
      hematopoietic and lymphopoietic responses in the hGM-CSFR Tg-mice. Administration
      of this factor to Tg-mice resulted in dose-dependent increases in numbers of
      reticulocytes and white blood cells (WBCs) in the peripheral blood. Morphological
      analysis of WBCs showed that the numbers of all types of the cell, including
      neutrophils, eosinophils, monocytes, and lymphocytes increased; the most
      remarkable being in lymphocytes that contained a number of large granular
      lymphocytes (LGLs) in addition to mature T and B cells. However, total
      cellularity of the BM of the Tg-mice decreased in a dose-dependent manner when
      hGM-CSF was injected. In sharp contrast to the BM, spleens of the Tg-mice were
      grossly enlarged. Although all types of blood cells and hematopoietic progenitors
      increased in the spleen, erythroid cells and their progenitors showed the most
      significant increase. Increased numbers of megakaryocytes and LGLs were also
      observed in spleen and liver of the treated Tg-mice. Flow cytometric analysis
      showed that LGLs expanded in Tg-mice expressed Mac-1+ CD3- NK1.1+. The thymus of
      Tg-mice treated with hGM-CSF exhibited a dose-dependent shrinkage and a
      remarkable decrease in CD4+ CD8+ cells. Thus, hGM-CSF stimulated not only
      myelopoiesis but also erythropoiesis and megakaryopoiesis of hGM-CSFR Tg-mice in
      vivo, in accordance with our reported in vitro findings. In addition, hGM-CSF
      affected the development of lymphoid cells, including natural killer cells of
      these Tg-mice.

PMID- 9242534
TI  - Expression of prostacyclin receptor in human megakaryocytes.
AB  - Prostacyclin (prostaglandin I2, PGI2) is a potent vasodilator and inhibitor of
      platelet aggregation. Although it is well known that the specific receptor for
      prostacyclin (PGI2-R) is abundantly expressed on platelets, PGI2-R expression in
      megakaryocytes is poorly understood. In this study, we examined its expression in
      leukemic or normal megakaryocytes. PGI2-R mRNA was expressed in human leukemic
      cell lines of megakaryocytic nature as evaluated by Northern blot analysis.
      Phorbol 12-myristate 13-acetate (PMA), interleukin-1 (IL-1), IL-3, IL-6,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), thrombopoietin (TPO),
      and tumor necrosis factor-alpha (TNF-alpha) enhanced PGI2-R mRNA expression. The
      enhancement of PGI2-R expression by PMA and TPO was associated with the
      upregulation of platelet factor 4 or glycoprotein IIb mRNA expression. Iloprost,
      an agonist of prostacyclin, induced significant cyclic (c)AMP synthesis in these
      leukemic cells indicating that interaction of PGI2-R and its ligand can induce
      postreceptor signal transduction. Furthermore, iloprost-induced cAMP synthesis
      was enhanced by the pretreatment with PMA or the cytokines that promoted PGI2-R
      expression. PMA and TPO also increased the specific binding of [3H]iloprost to
      these cells. Pooled normal megakaryocytic colonies from TPO-containing semisolid
      culture of purified human CD34+ cells expressed PGI2-R, which were increased as
      the megakaryocytes matured with the peak expression before proplatelet formation,
      as evaluated by semiquantitative reverse transcription-polymerase chain reaction
      (RT-PCR). These results indicate that PGI2-R is expressed in human megakaryocytes
      and is upregulated by cytokines involved in thrombopoiesis or inflammation. Also,
      it was indicated that megakaryocytic maturation accompanies enhancement of PGI2-R
      expression.

PMID- 9242535
TI  - The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder characterized by
      developmental defects, bone marrow failure, and cancer susceptibility. Cells
      derived from FA patients are sensitive to crosslinking agents and have a
      prolonged G2 phase, suggesting a cell cycle abnormality. Although transfection of
      type-C FA cells with the FAC cDNA corrects these cellular abnormalities, the
      molecular function of the FAC polypeptide remains unknown. In the current study
      we show that expression of the FAC polypeptide is regulated during cell cycle
      progression. In synchronized HeLa cells, FAC protein expression increased during
      S phase, was maximal at the G2/M transition, and declined during M phase. In
      addition, the FAC protein coimmunoprecipitated with the cyclin-dependent kinase,
      cdc2. We next tested various mutant forms of the FAC polypeptide for binding to
      cdc2. A patient-derived mutant FAC polypeptide, containing a point mutation at
      L554P, failed to bind to cdc2. The FAC/cdc2 binding interaction therefore
      correlated with the functional activity of the FAC protein. Moreover, binding of
      FAC to cdc2 was mediated by the carboxyl-terminal 50 amino acids of FAC in a
      region of the protein required for FAC function. Taken together, our results
      suggest that the binding of FAC and cdc2 is required for normal G2/M progression
      in mammalian cells. Absence of a functional interaction between FAC and cdc2 in
      FA cells may underlie the cell cycle abnormality and clinical abnormalities of
      FA.

PMID- 9242536
TI  - A comparison of murine and human factor XI.
AB  - Factor XI is a plasma glycoprotein that is required for contact activation
      initiated fibrin formation in vitro and for normal hemostasis in vivo. In
      preparation for developing a mouse model of factor XI deficiency to facilitate
      investigations into this protease's contributions to coagulation, we cloned the
      complementary DNA for murine factor XI, expressed the protein in a mammalian
      expression system, and compared its properties with human recombinant factor XI.
      The 2.8-kb murine cDNA codes for a protein of 624 amino acids with 78% homology
      to human factor XI. Both recombinant murine and human factor XI are 160 kD
      homodimers comprised of two 80 kD polypeptides connected by disulfide bonds.
      Murine factor XI shortens the clotting time of human factor XI deficient plasma
      in an activated partial thromboplastin time assay, with a specific activity 50%
      to 70% that of the human protein. In a purified system, murine factor XI is
      activated by human factor XIIa and thrombin in the presence of dextran sulfate.
      Murine factor XI differs from human factor XI in that it undergoes autoactivation
      slowly in the presence of dextran sulfate. This is due primarily to murine factor
      XIa preferentially cleaving a site on zymogen factor XI within the light chain,
      rather than the activation site between Arg371 and Val372. Northern blots of
      polyadenylated messenger RNA show that murine factor XI message is expressed, as
      expected, primarily in the liver. In contrast, messenger RNA for human factor XI
      was identified in liver, pancreas, and kidney. The studies show that murine and
      human factor XI have similar structural and enzymatic properties. However, there
      may be variations in tissue specific expression and subtle differences in enzyme
      activity across species.

PMID- 9242537
TI  - Human neutrophil elastase activates human factor V but inactivates thrombin
      activated human factor V.
AB  - The effect of human neutrophil elastase (HNE) on human factor V (F.V) or alpha
      thrombin-activated human factor V (F.Va) was studied in vitro by prothrombinase
      assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and
      NH2-terminal sequence analysis. Incubation of F.V (600 nmol/L) with HNE (2
      nmol/L) in the presence of Ca2+ resulted in a time-dependent increase in its
      cofactor activity. In contrast, treatment of F.Va (600 nmol/L) with HNE (60
      nmol/L) in the presence of Ca2+ resulted only in a time-dependent decrease in its
      cofactor activity. Under the conditions of these experiments, the maximum extent
      of F.V activation accomplished by incubation with HNE was approximately 65% to
      70% of that observed with alpha-thrombin in presence of Ca2+. The extent of both
      the HNE-dependent enhancement in F.V cofactor activity and the HNE-dependent
      decrease in F.Va cofactor activity was not influenced by the addition of
      phosphatidylcholine/phosphatidylserine (PCPS) vesicles (50 micromol/L). The HNE
      derived cleavage products of F.V, which correlated with increased cofactor
      activity, as demonstrated by SDS-PAGE under reducing conditions, were different
      from those generated using alpha-thrombin. Treatment of F.V (600 nmol/L) with HNE
      (2 nmol/L) in the presence of Ca2+ resulted in the production of three closely
      spaced doublets of: 99/97, 89/87, and 76/74 kD whose appearance over time
      correlated well with the increased cofactor activity as judged by densitometry.
      Treatment of F.Va (600 nmol/L) with HNE (60 nmol/L) in the presence of Ca2+
      resulted in the cleavage of both the 96 kD heavy chain and the 74/72 kD light
      chain into products of: 56, 53, 35, 28, 22, and 12 kD. Although densitometry
      indicated that both the heavy and light chains of F.Va were hydrolyzed by HNE,
      cleavage of the 96 kD heavy chain was more extensive during the time period (10
      to 30 minutes) of the greatest loss of F.Va cofactor activity. NH2-terminal
      sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and
      Ile1484 under conditions during which the procofactor expressed enhanced cofactor
      activity in the prothrombinase complex. NH2-terminal sequence analysis of F.Va
      treated with HNE indicated cleavage at Ala341, Ile508, and Thr1767 under
      conditions, which the cofactor became inactivated, as measured by prothrombinase
      activity. The activation and inactivation cleavage sites are close to those
      cleaved by the physiological activator and inactivator of F.V and F.Va, namely
      alpha-thrombin (Arg709 and Arg1545) and Activated Protein C (APC) (Arg306 and
      Arg506), respectively. These results indicate that HNE can generate proteolytic
      products of F.V, which initially express significantly enhanced procoagulant
      cofactor activity similar to that observed following activation with alpha
      thrombin. In contrast, HNE treatment of F.Va resulted only in the loss of its
      cofactor activity, but again, this is similar to that observed following
      inactivation by APC.

PMID- 9242538
TI  - Persistent systemic production of human factor IX in mice by skeletal myoblast
      mediated gene transfer: feasibility of repeat application to obtain therapeutic
      levels.
AB  - Myoblast-mediated gene transfer and its repeated applications were tested for
      achieving a long-term stable systemic production of human factor IX (hFIX) at a
      therapeutic level in SCID mice. Primary skeletal myoblasts were stably
      transfected with a hFIX expression plasmid vector, pdLMe4 betaA-hIXm1, which
      contains a hFIX minigene under the control of a beta-actin promoter with muscle
      creatine kinase enhancers. Myotubes derived from the myoblasts produced 1,750 ng
      hFIX/10(6) cells/24 hours in culture. hFIX secretion by the myoblasts and thereof
      derived myotubes were equally efficient, and myotubes were shown to have a
      sufficient secretory capacity to handle a substantially elevated production of
      hFIX. After intramuscular injection of 5, 10, and 20 x 10(6) myoblasts, SCID mice
      stably produced hFIX into the systemic circulation proportional to the number of
      implanted cells, and the expression levels were maintained for at least up to 10
      months (end of the experiment). Additional cell injections administered to
      animals that originally received 10 x 10(6) cells approximately 2 months later
      elevated the systemic hFIX levels to an average of 182 +/- 21 ng/mL, a
      therapeutic level, which persisted for at least 8 months (end of the experiment).
      These results indicate that long-term, stable systemic production of hFIX at
      therapeutic levels can be achieved by repeated application of myoblast-mediated
      gene transfer.

PMID- 9242539
TI  - HLA class II restricted T-cell reactivity to a developmentally regulated antigen
      shared by leukemic cells and CD34+ early progenitor cells.
AB  - After allogeneic bone marrow transplantation (BMT), the beneficial graft-versus
      leukemia (GVL) effect but also the life-threatening graft-versus-host disease
      (GVHD) are mediated by T cells of the grafted marrow. The identification of
      leukemia cell-reactive T cells and their ligands are, therefore, crucial for the
      development of new anti leukemia strategies. Here we describe a leukemia-reactive
      allo-HLA class II restricted CD4+ T-cell clone, 6.2, isolated from a healthy
      individual after stimulation with allogeneic leukemic cells. Clone 6.2 recognizes
      leukemic cells from several AML patients without showing reactivity to
      unfractioned peripheral blood mononuclear cells, monocytes, B cells, T-cell
      blasts, and proximal tubulus epithelial cells. Interestingly, clone 6.2 also
      recognizes BM cells derived from healthy individuals and inhibits the colony
      formation of myeloid and erythroid cell lineages. In the BM, clone 6.2 recognizes
      only CD34+ early precursor cells but not CD34-, more differentiated cells. Thus,
      the target antigen of clone 6.2 is developmentally regulated and expressed only
      by leukemic cells and CD34+ early progenitor cells in the hematopoietic system.
      We suggest that targeting the T-cell immune response to leukemia-associated,
      developmentally regulated antigens of the hematopoietic system can provide a
      basis for the separation of GVL from GVHD, and may lead to new therapeutic
      approaches for residual and relapsed leukemia.

PMID- 9242540
TI  - The acquisition of host-derived major histocompatibility complex class II
      glycoproteins by human immunodeficiency virus type 1 accelerates the process of
      virus entry and infection in human T-lymphoid cells.
AB  - Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive
      depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The
      mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely
      understood. However, several lines of evidence indicate that direct cytopathology
      mediated by HIV-1 is a key element in such CD4+ T-cell depletion. In this study,
      we investigated whether the previously reported incorporation of host-derived
      major histocompatibility class II glycoproteins (MHC-II) on HIV-1 can alter its
      replicative capacity. To achieve this goal, virus stocks were produced in
      parental MHC-II-expressing RAJI cells and in MHC-II-negative RAJI mutants (RM3),
      both of which have been stably transfected with human CD4 cDNA to allow
      productive infection with HIV-1. An enhancement of the rate/efficiency of virus
      entry was seen after infection with normalized amounts of virions carrying host
      derived MHC-II on their surface as compared with inoculation with virions devoid
      of cellular MHC-II. Data from time-course and infectivity experiments showed that
      the kinetics of infection were more rapid for virions bearing host-derived MHC-II
      glycoproteins than for MHC-II-free HIV-1 particles. These results suggest that
      virally embedded cellular MHC-II glycoproteins are functional and can have a
      positive effect on early events in the virus replicative cycle. Therefore, we
      show that the acquisition of cellular MHC-II glycoproteins by HIV-1 can modify
      its biologic properties and might, consequently, influence the pathogenesis of
      this retroviral disease.

PMID- 9242541
TI  - The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1
      receptor antagonist and IL-1 soluble receptor type II in acute meningococcal
      infections.
AB  - Interleukin-1beta (IL-1beta) is considered an important mediator in the
      pathogenesis of septic shock or bacterial meningitis. Its activity is
      specifically modulated by IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble
      receptor type II (IL-1sRII). We now describe the time-course of IL-1beta and
      these modulating agents in 59 patients with acute meningococcal infections, the
      prototype human disease of acute endotoxin exposure. Plasma IL-1beta was
      increased only in severe shock and normalized within 12 to 24 hours, indicating
      that patients were admitted in an early stage of cytokine activation. Increased
      IL-1beta values in cerebrospinal fluid (CSF) were confined to patients with
      meningitis. Plasma IL-1Ra was elevated in both shock and nonshock patients,
      extremely high values being measured in severe shock. High concentrations of IL
      1Ra in CSF were found in meningitis. Plasma IL-1Ra peaked shortly after IL-1beta
      and decreased steeply in 1 to 2 days, followed by sustained moderately elevated
      levels in shock patients. Interestingly, IL-1sRII showed a completely different
      pattern. At admission, both nonshock and shock patients manifested a similar
      moderate increase of plasma IL-1sRII. However, during recovery plasma IL-1sRII
      further increased reaching maximal concentrations 3 to 5 days after admission, 1
      to 2 days after normalization of IL-1Ra. In shock patients this increase was more
      prominent than in nonshock patients. It is hypothesized that this increase in
      plasma IL-1sRII can be explained by a synergistic effect of dexamethasone and
      endotoxin. A second interesting observation was that, unlike the pattern in
      plasma, IL-1sRII levels in CSF paralleled those of IL-1beta and IL-1Ra. This
      suggests different modulation of IL-1beta activity in the subarachnoid space and
      the plasma compartment. We conclude that: (1) During the early stage of
      meningococcal infections IL-1Ra modulates IL-1 activity, whereas during recovery
      IL-1sRII may be more important. (2) Modulation in CSF and in the plasma
      compartment are differentially regulated.

PMID- 9242542
TI  - Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer
      cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype.
AB  - We analyzed a genetic polymorphism of Fc gamma receptor IIIa (CD16) that is
      present on position 158 (Phe or Val) in the membrane-proximal, IgG-binding
      domain. With a polymerase chain reaction-based allele-specific restriction
      analysis assay we genotyped 87 donors and found gene frequencies of 0.57 and 0.43
      for Fc gammaRIIIA-158F and -158V, respectively. A clear linkage was observed
      between the Fc gammaRIIIA-158F and -48L genotypes on the one hand and the Fc
      gammaRIIIA-158V and -48H or -48R genotypes on the other hand (chi2 test; P <
      .001). To determine the functional consequences of this Fc gammaRIIIa-158V/F
      polymorphism, we performed IgG binding experiments with natural killer (NK) cells
      from genotyped donors. All donors were also typed for the recently described
      triallelic Fc gammaRIIIa-48L/R/H polymorphism. NK cells were treated with lactic
      acid to remove cell-associated IgG. Fc gammaRIIIa(NK)-158F bound significantly
      less IgG1, IgG3, and IgG4 than did Fc gammaRIIIa(NK)-158V, irrespective of the Fc
      gammaRIIIa-48 phenotype. Moreover, freshly isolated NK cells from Fc gammaRIIIa
      158VV individuals carried significantly more cytophilic IgG than did NK cells
      from Fc gammaRIIIa-158FF individuals. In addition, CD16 monoclonal antibody
      (MoAb) MEM154 bound more strongly to Fc gammaRIIIa-158V, compared with -158F,
      again independently of the Fc gammaRIIIa-48 phenotype. The binding of MoAb B73.1
      was not influenced by the Fc gammaRIIIa-158V/F polymorphism, but proved to depend
      solely on the amino acid present at position 48 of Fc gammaRIIIa. In conclusion,
      the previously reported differences in IgG binding among the three Fc gammaRIIIa
      48L/R/H isoforms are a consequence of the linked, biallelic Fc gammaRIIIa-158V/F
      polymorphism at amino-acid position 158.

PMID- 9242543
TI  - Interleukin-15 triggers activation and growth of the CD8 T-cell pool in
      extravascular tissues of patients with acquired immunodeficiency syndrome.
AB  - The impairment of interleukin-2 (IL-2) production occurs very early after human
      immunodeficiency virus (HIV) infection as a consequence of the quantitative
      depletion of Th1 cells. Despite the shift in cytokine production, most
      individuals develop an oligoclonal expansion of major histocompatibility complex
      restricted, HIV-specific CD8+ cytotoxic T lymphocytes (CTL) in different organs,
      suggesting that other cytokines replace IL-2 in initiating the tissue
      infiltration of CD8+ T cells. In this study we show that IL-15, a product of
      monocyte-macrophages and non-T cells and which has overlapping biological
      activities with IL-2, is involved in local cell networks accounting for the
      activation and expansion of CD8+ T-cell pools in a highly affected organ, ie, the
      lung. IL-15 induced proliferation of T cells obtained from the lower respiratory
      tract of HIV-infected patients with T-cell alveolitis and severe depletion of
      CD4+ T cells. Lung lymphocytes were CD45R0+/CD8+ T cells spontaneously expressing
      activation markers (CD69 and HLA-DR) and equipped with the receptorial subunits
      which bind IL-15, notably the beta and gamma chains of the IL-2 receptor (IL-2R)
      and the recently identified IL-15 binding-protein termed IL-15R alpha. Similar
      phenotypic findings were obtained after incubation of normal T cells with IL-15,
      which induced CD8+ T cells to express activation markers and to proliferate. The
      block of the IL-2R beta/IL-2R gamma complex with specific monoclonal antibodies
      abolished the T-cell stimulatory activity of IL-15 while the combination of IL-15
      and tumor necrosis factor-alpha upregulated the proliferative response of lung T
      lymphocytes. The hypothesis that the tissue growth of lung CD8+ lymphocytes may
      involve cytokines produced from cells other than T lymphocytes was confirmed by
      the evidence that pulmonary macrophages expressed high levels of IL-15 and that
      anti-IL-15 antibodies inhibited the accessory function of alveolar macrophages on
      mitogen-induced CD8+ T-cell proliferation. Together, these results suggest that
      macrophage-derived cytokines produced at sites of T-cell infiltration play a role
      in the activation of HIV-specific CD8+ T-cell-mediated immune response.

PMID- 9242544
TI  - N-acetyl-L-cysteine exhibits antitumoral activity by increasing tumor necrosis
      factor alpha-dependent T-cell cytotoxicity.
AB  - Because of its anticarcinogenic and antimutagenic properties, N-acetyl-L-cysteine
      (NAC) has been proposed for cancer treatment. Here we present a mechanism of
      action for NAC in cancer. Our data show that NAC (1) induces an early and
      sustained increase of membrane tumor necrosis factor alpha (TNF alpha) expression
      on human stimulated-peripheral blood (PB) T cells and (2) increases membrane TNF
      RI and TNF-RII on tumoral cell lines and on T cells after stimulation. These
      effects result from an early inhibition of both TNF alpha and TNF-R shedding, as
      well as a later increase of the respective mRNA expression. Consequently, NAC
      confers cytotoxic properties to human PB T cells through a membrane TNF alpha
      dependent pathway. In vivo, NAC given orally inhibits tumor appearance in more
      than a third (18 out of 50) B6D2F1 mice injected with L1210 lymphoma cells.
      Spleen cells from protected mice killed L1210 lymphoma cells in vitro in a
      membrane TNF alpha-dependent manner. Furthermore these mice were resistant to a
      second inoculation of L1210 cells without further treatment with NAC. Thus, NAC
      exhibits a potent antitumoral activity by modulating TNF alpha and TNF-R
      processing without showing any in vitro and in vivo toxicity.

PMID- 9242545
TI  - Even individuals considered as long-term nonprogressors show biological signs of
      progression after 10 years of human immunodeficiency virus infection.
AB  - Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few
      individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T
      cell count for a period of time. The aim of this study was to establish, through
      the sequential determination of all known predictors of HIV disease, the
      proportion of such patients having stringent criteria of true long-term
      nonprogression. Among 249 individuals who were HIV-infected and prospectively
      followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count
      greater than 500/microL (LTNP I group) and 9 having a CD4+ T-cell count less than
      500 but stable over time (LTNP II group) after at least 10 years of infection
      without intervention of antiviral therapy, were studied over the entire follow-up
      period. The plasma HIV RNA copy number and the serum concentrations of p24
      antigen, each anti-HIV antibody, neopterin, beta-2-microglobulin, Immunoglobulin
      (Ig) G and IgA were determined every 18 months over the study period. Cellular
      and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two
      patients had strictly no marker of progression over the follow-up period. They
      were the only ones who had, over the 10-year period, a viral copy number too low
      to be detected. The other patients had a viral copy number higher than 400/mL at
      at least one visit and increasing over the follow-up period, and they evidenced
      one or more markers of virological or immunological deterioration. Cellular
      viremia was positive in all patients but two, while plasma viremia was negative
      in all but one. The population of individuals termed as LTNPs is not
      virologically and immunologically homogeneous. The majority present biological
      signs of HIV disease progression. A new pattern of true LTNP can be drawn through
      stringent criteria based on the whole known predictors. This pattern appears to
      be rare in HIV-positive population.

PMID- 9242546
TI  - Inhibition of human immunodeficiency virus type 1 infectivity by secretory
      leukocyte protease inhibitor occurs prior to viral reverse transcription.
AB  - Infection of monocytes with human immunodeficiency virus type 1(Ba-L) (HIV-1(Ba
      L)) is significantly inhibited by treatment with the serine protease inhibitor,
      secretory leukocyte protease inhibitor (SLPI). SLPI does not appear to act on
      virus directly, but rather the inhibitory activity is most likely due to
      interaction with the host cell. The current study was initiated to investigate
      how SLPI interacts with monocytes to inhibit infection. SLPI was found to bind to
      monocytes with high affinity to a single class of receptor sites (approximately
      7,000 receptors per monocyte, K(D) = 3.6 nmol/L). The putative SLPI receptor was
      identified as a surface protein with a molecular weight of 55 +/- 5 kD. A well
      characterized function of SLPI is inhibition of neutrophil elastase and cathepsin
      G. However, two SLPI mutants (or muteins) that contain single amino acid
      substitutions and exhibit greatly reduced protease inhibitory activity still
      bound to monocytes and retained anti-HIV-1 activity. SLPI consists of two
      domains, of which the C-terminal domain contains the protease inhibiting region.
      However, when tested independently, neither domain had potent anti-HIV-1
      activity. SLPI binding neither prevented virus binding to monocytes nor
      attenuated the infectivity of any virus progeny that escaped inhibition by SLPI.
      A polymerase chain reaction (PCR)-based assay for newly generated viral DNA
      demonstrated that SLPI blocks at or before viral DNA synthesis. Therefore, it
      most likely inhibits a step of viral infection that occurs after virus binding
      but before reverse transcription. Taken together, the unique antiviral activity
      of SLPI, which may be independent of its previously characterized antiprotease
      activity, appears to reside in disruption of the viral infection process soon
      after virus binding.

PMID- 9242547
TI  - CD44 is involved in tumor angiogenesis; an activation antigen on human
      endothelial cells.
AB  - CD44 is described to be an activation molecule in a number of different cell
      types. We investigated the role of CD44 on human endothelial cells (EC) and in
      tumor angiogenesis. Using flow cytometry we showed that EC from the vasculature
      of human solid tumors display an enhanced expression of CD44 as compared to EC
      from normal tissue. This finding was confirmed by immunohistochemical studies on
      frozen tissue sections. Because tumors are dependent on angiogenesis, the role of
      angiogenic stimuli in the enhanced CD44 expression was investigated. We found
      that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor
      were able to efficiently upregulate CD44 expression on cultured human EC. The
      upregulation reached maximal levels after treatment for 3 days with 10 ng/mL
      bFGF. The physiological impact of this upregulation was shown by the enhanced
      binding of EC to hyaluronate after pretreatment with bFGF. In a next set of
      studies that were designed to unravel the regulation of CD44 expression on EC we
      concluded that CD44 is an activation antigen on human EC since (1) human
      umbilical vein derived endothelial cells, which in vivo do not express CD44,
      begin to express CD44 when plated and cultured, (2) CD44 expression is enhanced
      after subculture of confluent cultures, (3) CD44 is predominantly expressed on
      the BrdU incorporating subset of cultured EC. The specific expression of CD44 on
      activated and tumor EC prompted us to study the usefulness of CD44 as an
      endothelial target for therapy with immunotoxins. In vitro experiments showed
      that EC are efficiently killed after targeting immunotoxin to CD44.

PMID- 9242548
TI  - Endogenously produced nitric oxide increases tumor necrosis factor-alpha
      production in transfected human U937 cells.
AB  - Various functions of human phagocytes are modulated by nitric oxide (NO). We
      transfected the human U937 monoblastoid cell line with an expression vector
      containing human endothelial NO synthase (eNOS) or murine inducible NOS (iNOS)
      cDNA to study the regulatory role of NO without the nonspecific effects
      associated with exogenous NO sources. Western blot confirmed expression of eNOS
      or iNOS in respectively transfected cells, but not in naive or empty-vector
      transfected cells. Transfectants expressing iNOS, a calcium-independent enzyme,
      but not eNOS, a calcium-dependent enzyme, spontaneously produced NO (P < .001).
      The NO release from iNOS-transfected cells, as measured by nitrite and nitrate
      accumulation and by cyclic guanosine monophosphate (cGMP) increases in rat
      reporter cells, was inhibitable (P < .01 for both) with N(omega)-methyl-L
      arginine (L-NMA), a NOS inhibitor. The eNOS transfectants were shown to contain
      functional enzyme by the conversion of L-arginine to L-citrulline in fractionated
      cells (P = .0001) and by exposing intact cells to calcium ionophore using the
      cGMP reporter cell assay (P = .0001). After differentiation with phorbol-12
      myristate-13-acetate (PMA), iNOS transfectants produced more tumor necrosis
      factor-alpha (TNF-alpha) (124.9 +/- 25.4 pg/5 x 10(5) cells per 24 hours) than
      did empty-vector transfected cells (21.9 +/- 1.9 pg/5 x 10(5) cells per 24 hours;
      P = .02). This effect was inhibited by 500 micromol/L L-NMA (54.4 +/- 3.1 pg/5 x
      10(5) cells per 24 hours; P = .05). However, in the presence of high
      concentrations of lipopolysaccharide (1 microg/mL), which further increased NO
      production in iNOS transfected cells (P = .044), TNF-alpha production was similar
      comparing PMA-differentiated iNOS and empty-vector transfectants (12.2 +/- 0.8
      and 13.1 +/- 1.7 ng/5 x 10(5) cells per 24 hours, respectively; P = .5). The
      results show that under certain conditions endogenously produced NO can
      upregulate TNF-alpha production in human phagocytes.

PMID- 9242549
TI  - BCL2 overexpression associated with chromosomal amplification in diffuse large B
      cell lymphoma.
AB  - Gene activation by translocation between an oncogene and an immunoglobulin heavy
      chain gene, which leads to increased expression of the oncoprotein, is a well
      known mechanism in the genesis of B-cell lymphomas. In contrast, the role of gene
      amplification in activation of oncogenes in non-Hodgkin's lymphomas is poorly
      characterized. To study the BCL2 amplification we performed comparative genomic
      hybridization (CGH), Southern blot hybridization, Western analysis,
      immunohistochemistry, metaphase fluorescence in situ hybridization, and
      chromosome analysis on 26 cases of diffuse large B-cell lymphoma (large
      noncleaved cell lymphoma). The gain or high-level amplification of 18q was found
      in eight tumors (31%) by CGH, and Southern analysis revealed BCL2 amplification
      in these cases, but not in the cases with normal chromosome 18 or
      t(14;18)(q32;q21). Western immunoblot analysis and immunohistochemistry revealed
      a high-level expression of BCL2 protein in the cases with BCL2 amplification and
      t(14;18)(q32;q21). However, translocation (14;18)(q32;q21) was not detected in
      any of the cases with BCL2 amplification. Therefore, our results suggest that
      amplification of the BCL2 gene is an important mechanism for BCL2 protein
      overexpression in diffuse large B-cell lymphoma.

PMID- 9242550
TI  - Characterization of the retinoid binding properties of the major fusion products
      present in acute promyelocytic leukemia cells.
AB  - The bcr1- and bcr3- promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR
      alpha) are the two major fusion proteins expressed in acute promyelocytic
      leukemia (APL) patients. These proteins, which are present in different lengths
      of PML (amino acids 1-552 and 1-394, respectively), contain most of the
      functional domains of PML and RAR alpha, bind all-trans-retinoic acid (t-RA), and
      act as t-RA-dependent transcription factors. T-RA is an effective inducer of
      clinical remission only in patients carrying the t(15;17) and expressing the
      PML/RAR alpha products. However, in APL patients achieving complete remission
      with t-RA therapy the bcr3-PML/RAR alpha product has been found associated with a
      poorer prognosis than bcr1-PML/RAR alpha. In the present study we have
      investigated the structural and functional properties of the bcr3-PML/RAR alpha
      in comparison to the previously characterized bcr1-PML/RAR alpha. In particular,
      we have measured the binding properties of the two endogenous ligands t-RA and 9
      cis-RA to both of these isoforms. T-RA binding analysis of nuclear and cytosolic
      extracts prepared from bcr3-PML/RAR alpha APL patients and from bcr3-PML/RAR
      alpha COS-1 transfected cells indicates that this protein is present only as high
      molecular-weight nuclear complexes. Using saturation binding assays and Scatchard
      analyses we found that t-RA binds with slightly less affinity to the bcr3-PML/RAR
      alpha receptor than to bcr1-PML/RAR alpha or RAR alpha (Kd = 0.4 nmol/L, 0.13
      nmol/L or 0.09 nmol/L, respectively). Moreover, two different high-affinity 9-cis
      RA binding sites (Kd = 0.45 and 0.075 nmol/L) were detectable in the bcr3-PML/RAR
      alpha product but not in the bcr1-PML/RAR alpha product (Kd = 0.77 nmol/L). By
      competition binding experiments we showed that 9-cis-RA binds with higher
      specificity to the bcr3-PML/RAR alpha isoform than to the bcr1-PML/RAR alpha or
      RAR alpha. Consistent with these data, the binding of 9-cis-RA to the bcr3
      PML/RAR alpha product resulted in increased transcriptional activation of the RA
      responsive element (RARE) TRE, but not of the betaRARE, in transiently
      transfected COS-1 cells. These results provide evidence indicating that
      preferential retinoid binding to the different PML/RAR alpha products can be
      measured.

PMID- 9242551
TI  - Epstein-Barr virus latent gene expression in primary effusion lymphomas
      containing Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8.
AB  - Primary effusion (body cavity-based) lymphoma (PEL) is a recently recognized
      subtype of malignant lymphoma that exhibits distinctive clinical and biological
      features, most notably its usual infection with the Kaposi's sarcoma-associated
      herpesvirus (KSHV). The vast majority of cases also contain Epstein-Barr virus
      (EBV). This dual viral infection is the first example of a consistent dual
      herpesviral infection in a human neoplasm and provides a unique model to study
      viral interactions. We analyzed the pattern of EBV latent gene expression to
      determine the pathogenic role of this agent in PELs. We examined five PELs
      coinfected with EBV and KSHV by reverse transcription-polymerase chain reaction
      (RT-PCR), in situ hybridization, and immunohistochemistry. EBER1 mRNA, a
      consistent marker of viral latency, was positive in all PEL cases, although at
      lower levels than in the non-PEL controls due to EBER1 expression by only a
      variable subset of lymphoma cells. Qp-initiated mRNA, encoding only EBNA1 and
      characteristic of latencies I and II, was positive in all PEL cases. Wp- and Cp
      initiated mRNAs, encoding all EBNAs and characteristic of latency III, were
      negative in all cases. LMP1 mRNA, expressed in latencies II and III, was present
      in three cases of PEL, although at very low levels that were not detectable at
      the protein level by immunohistochemistry. Low levels of LMP2A mRNA were detected
      in all cases. BZLF1, an early-intermediate lytic phase marker, was weakly
      positive in four cases, suggesting a productive viral infection in a very small
      proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore,
      PELs exhibit a restricted latency pattern, with expression of EBNA1 in all cases,
      and low LMP1 and LMP2A levels.

PMID- 9242552
TI  - Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid
      leukemia with t(16;21)(p11;q22) and identification of a novel transcript.
AB  - 16;21 translocation is a recurrent primary abnormality in acute myeloid leukemia
      (AML). The genes involved in this translocation are ERG on chromosome 21 and
      TLS/FUS on chromosome 16. The rearrangement of the two chromosomes forms the
      TLS/FUS-ERG fusion gene and produces a consistent chimeric transcript on the der
      (21) chromosome. In this study, we analyzed the clinical characteristics of 19
      patients with t(16;21)-AML, including 2 patients who evolved from myelodysplastic
      syndrome, and detected the chimeric transcripts of the TLS/FUS-ERG fusion gene in
      the patients during various clinical stages by the reverse transcriptase
      polymerase chain reaction (RT-PCR) technique. We found that the patients with
      t(16;21) are characterized by a relatively younger age (median age, 22 years
      old), involvement of various subtypes of French-American-British classification
      and a poor prognosis: 18 of the 19 patients died of the disease (median survival
      was 16 months). Four types of TLS/FUS-ERG chimeric transcripts including a novel
      type were noted in the RT-PCR analysis. The novel transcript contained an
      additional 138 nucleotides consisting of TLS/FUS exon 8 and ERG exons 7 and 8 and
      had an in-frame fusion. These chimeric transcripts were consistently detectable
      in the samples obtained not only at diagnosis and relapse but also in short and
      long complete remission, suggesting that t(16;21)-AML is resistant to
      conventional chemotherapy. Thus, we recommend that t(16;21) should be monitored
      by RT-PCR even in clinical remission and the patients should be treated by other
      more powerful modality like stem-cell transplantation in the first remission.

PMID- 9242553
TI  - Human herpesvirus 6 (HHV-6)-positive Burkitt's lymphoma: establishment of a novel
      cell line infected with HHV-6.
AB  - Human herpesvirus 6 (HHV-6) DNA has been detected in several human
      lymphoproliferative disorders. We report a case of HHV-6-infected Burkitt's
      lymphoma, from which a cell line, designated Katata, has been established. Katata
      cells had an immature B-cell phenotype with an L3 morphology and carried a
      t(8;14)(q24;q32) chromosomal abnormality. The HHV-6 DNA sequences were detected
      in both the patient's tumor cells and Katata cell line by polymerase chain
      reaction using three sets of primers that target different regions of HHV-6 DNA.
      The presence of HHV-6 DNA in Katata cells was also shown by Southern blot
      hybridization with the BamHI fragment of HHV-6. It is likely that the virus is in
      a latent state, since (1) virion-associated protein was not expressed in Katata
      cells, (2) transcriptional level of the immediate-early gene was very low, and
      (3) no viral particles were observed by electron microscopy. Katata cells were
      highly tumorigenic in nude mice and the tumor cells also contained HHV-6 DNA. We
      have successfully obtained several clonal lines by allowing the cells to form
      colonies in soft agarose and by the limiting dilution method. HHV-6 DNA was
      detectable in all 13 clones analyzed, suggesting that virtually all Katata cells
      are infected with HHV-6. This is the first report of a case of HHV-6+ Burkitt's
      lymphoma in the absence of Epstein-Barr virus. Furthermore, there has been no
      report of lymphoma cell lines that are persistently and nonproductively infected
      with HHV-6. The Katata Burkitt's lymphoma cell line, therefore, would provide a
      useful tool for studies of the mechanisms of HHV-6 latency and reactivation.

PMID- 9242554
TI  - Bcl-2 and Bcl-XL can differentially block chemotherapy-induced cell death.
AB  - Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors and their
      expression modulates the sensitivity of tumor cells to a wide spectrum of
      chemotherapeutic agents and gamma-irradiation. In the present report, we
      generated clones of FL5.12 lymphoid cells with similar levels of Bcl-2 and Bcl-XL
      using the Flag epitope to determine if these survival proteins could provide
      equivalent protection when challenged with chemotherapy or gamma-irradiation.
      Using four M-phase specific chemotherapeutic agents, Bcl-XL and Bcl-2 provided
      similar protection against vincristine and vinblastine whereas Bcl-XL afforded as
      much as 50% greater cell viability than Bcl-2 against etoposide and teniposide
      induced cell death. In addition, Bcl-XL provided significantly greater cell
      viability than Bcl-2 against methotrexate, fluorouracil, and hydroxyurea, three S
      phase specific agents. In apoptosis induced by gamma-irradiation and cisplatin,
      two antitumor treatments that are cell-cycle phase-nonspecific agents, both Bcl
      XL and Bcl-2 conferred similar protection against gamma-irradiation, but Bcl-XL
      provided better protection than Bcl-2 against cisplatin. These results indicate
      that Bcl-XL and Bcl-2 confer a differential ability to protect against
      chemotherapy-induced cell death, which appears to be dependent on the molecular
      mechanism targeted by the drug rather than its cell-cycle phase specificity.

PMID- 9242555
TI  - High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are
      associated with a worse long-term outcome.
AB  - The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA
      binding protein with predominantly transcription repressing properties. Because
      wt1 has been shown to be expressed in the vast majority of patients with acute
      myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression
      regarding prognosis and possible prediction of relapse during follow-up. Totally
      bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients,
      22 AML patients again in first relapse, and 10 AML patients analyzed primarily in
      first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were
      analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse
      transcription-polymerase chain reaction (RT-PCR) was performed and the
      amplification product was visually classified as not, weakly, moderately, or
      strongly amplified, as described previously. PCR products were quantitated by
      competitive PCR using a shortened homologous wt1 construct standard in
      representative cases. The expression of wt1 transcripts was correlated to age,
      French-American-British (FAB) subtype, phenotype, karyotype, and long-term
      survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in
      first relapse. wt1 expression was independent from age, antecedent
      myelodysplastic syndrome or FAB subtype, with the exception of a significant
      difference in M5 leukemias showing wt1 transcripts in only 40% (P = .0025). There
      was no correlation between the level of wt1 mRNA and response to treatment or the
      prognostic groups defined by the karyotype. Concerning long-term survival,
      patients with high levels of wt1 had a significantly worse overall survival (OS)
      than those with not detectable or low levels. The 3-year OS for all newly
      diagnosed AMLs was 13% and 38% (P = .038), respectively, and 12% and 43% (P =
      .014) for de novo AMLs. The difference was more distinct in patients less than 60
      years of age. During follow-up, all patients achieving complete remission became
      wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data
      indicate that high expression of wt1 mRNA is associated with a worse long-term
      prognosis.

PMID- 9242556
TI  - Detectable molecular residual disease at the beginning of maintenance therapy
      indicates poor outcome in children with T-cell acute lymphoblastic leukemia.
AB  - The aims of this study were twofold: (1) to assess the marrow of patients with T
      lineage acute lymphoblastic leukemia (T-ALL) for the presence of molecular
      residual disease (MRD) at different times after diagnosis and determine its value
      as a prognostic indicator; and (2) to compare the sensitivity, rapidity, and
      reliability of two methods for routine clinical detection of rearranged T-cell
      receptor (TCR). Marrow aspirates from 23 patients with T-ALL diagnosed
      consecutively from 1982 to 1994 at the Division of Pediatric Hematology and
      Oncology, University of Catania, Italy, were obtained at diagnosis, at the end of
      induction therapy (6 to 7 weeks after diagnosis), at consolidation and/or
      reinforced reinduction (12 to 15 weeks after diagnosis), at the beginning of
      maintenance therapy (34 to 40 weeks after diagnosis), and at the end of therapy
      (96 to 104 weeks after diagnosis). DNA from the patients' marrow was screened
      using the polymerase chain reaction (PCR) for the four most common TCR delta
      rearrangements in T-ALL (Vdelta1 Jdelta1, Vdelta2 Jdelta1, Vdelta3 Jdelta1, and
      Ddelta2 Jdelta1) and, when negative, further tested for the presence of other
      possible TCR delta and TCR gamma rearrangements. After identification of
      junctional rearrangements involving V, D, and J segments by DNA sequencing, clone
      specific oligonucleotide probes 5' end-labeled either with fluorescein or with
      [gamma-32P]ATP were used for heminested PCR or dot hybridization of PCR products
      of marrows from patients in clinical remission. For 17 patients with samples that
      were informative at the molecular level, the estimated relapse-free survival
      (RFS) at 5 years was 48.6% (+/-12%). The sensitivity and specificity for
      detection of MRD relating to the outcome were 100% and 88.9% for the heminested
      fluorescence PCR and 71.4% and 88.9% for Southern/dot blot hybridization,
      respectively. Predictive negative and positive values were 100% and 90.7% for
      heminested fluorescence PCR, respectively. The probability of RFS based on
      evidence of MRD as detected by heminested fluorescence PCR at the time of
      initiation of maintenance therapy was 100% and 0% for MRD-negative and MRD
      positive patients, respectively. Thus, the presence of MRD at the beginning of
      maintenance therapy is a strong predictor of poor outcome, and the molecular
      detection of MRD at that time might represent the basis for a therapeutic
      decision about such patients. By contrast, the absence of MRD at any time after
      initiation of treatment strongly correlates with a favorable outcome. The
      heminested fluorescence PCR appears to be more accurate and more rapid than other
      previously used methods for the detection of residual leukemia.

PMID- 9242557
TI  - A chromosome 14q11/TCR alpha/delta specific yeast artificial chromosome improves
      the detection rate and characterization of chromosome abnormalities in T
      lymphoproliferative disorders.
AB  - The rate of detection of chromosome abnormalities in T-cell proliferations is
      lower than that observed in B-cell malignancies. The former frequently involve
      the TCR alpha/delta locus at chromosome band 14q11. We have identified a YAC
      encompassing 70% of the TCR alpha/delta locus, which has been used as a
      fluorescence in situ hybridization probe to detect chromosome rearrangements
      involving 14q11, both at metaphase and within interphase nuclei, in patients with
      a variety of T-lymphoproliferative disorders. Its use allowed detection of
      previously unsuspected TCR alpha/delta rearrangements in 4/13 (30%) immature T
      lineage acute leukemias, including two t(10;14) and 2 minor inversion 14s. It
      also clarified interpretation of complex chromosome 14 abnormalities in mature T
      cell proliferations (T-prolymphocytic leukemia and ataxia telangiectasia). Use of
      this probe will aid the detection and characterization of abnormalities involving
      the TCR alpha/delta locus, particularly in cases with normal or complex
      karyotypes and in those proliferations for which mitoses are difficult to obtain.

PMID- 9242559
TI  - Expression and intracellular localization of the human N-acetylmuramyl-L-alanine
      amidase, a bacterial cell wall-degrading enzyme.
AB  - N-acetylmuramyl-L-alanine amidase (NAMLAA) specifically degrades peptidoglycan,
      which is a major component of bacterial cell walls with strong inflammatory
      properties. For instance, peptidoglycan is capable of stimulating peripheral
      blood cells to release pro-inflammatory cytokines and is capable of inducing
      chronic arthritis in an animal model. In a previous study we found that
      degradation of peptidoglycan by purified NAMLAA reduced its inflammatory effects.
      To determine where NAMLAA is located in tissues, monoclonal antibodies against
      purified NAMLAA were produced for use in immunohistochemistry, immunoelectron
      microscopy, flow cytometric analysis, and Western blotting. The
      immunohistochemical studies showed NAMLAA-positive cells in human spleen, liver,
      arthritic synovial tissues, and lymph nodes. In flow cytometric studies of blood
      and bone marrow, neutrophilic and eosinophilic granulocytes proved to be
      positive. Monocytes were negative, although they do contain lysozyme, the other
      important peptidoglycan-degrading enzyme. However, mature macrophages obtained by
      bronchoalveolar lavage and subsequent selection based on autofluorescence did
      possess NAMLAA. In immunocytochemical staining of blood smears, thrombocytes were
      also positive for NAMLAA. Western blot analysis and immunoelectron microscopy of
      neutrophils and eosinophils showed that NAMLAA is located in azurophilic granules
      of neutrophils and in secretory vesicles and crystalloid-containing granules of
      eosinophils. Flow cytometric analysis of blood and bone marrow from different
      French-American-British-classified acute myeloid leukemia (AML) patients showed
      that AML-M2 myeloblasts were the first in the granulocyte maturation lineage that
      were positive for NAMLAA. The more immature AML, such as AML-M0 and AML-M1, did
      not express NAMLAA. CD15- and CD13-negative megakaryoblasts, corresponding to AML
      M7, were also positive for NAMLAA. The expression pattern of NAMLAA in the
      myeloid lineage suggests that the monoclonal antibody AAA4, recognizing NAMLAA,
      is useful for discrimination between AML in the monocyte lineage and in the
      granulocyte lineage.

PMID- 9242558
TI  - Disparate affinities of antifolates for folylpolyglutamate synthetase from human
      leukemia cells.
AB  - Previous work showed that acute myelocytic leukemia blasts accumulate less long
      chain polyglutamates of methotrexate (MTX) than acute lymphocytic leukemia blasts
      when incubated with this radiolabeled antifolate. This difference likely explains
      the increased sensitivity of lymphoid leukemias to short-term exposure of MTX as
      compared with myeloid leukemias. In this study, we examined the basis for
      differences between long chain MTX polyglutamate accumulation between different
      leukemia cell types using both leukemia cell lines and blasts freshly isolated
      from blood of leukemic patients. The major difference found between leukemia
      cells that accumulate long chain polyglutamates and those that do not were
      differences in Km values for the enzyme folylpolyglutamate synthetase. Km values
      did not change with partial purification of this enzyme, indicating that
      interfering substances in crude lysates were not responsible for this difference.
      We postulate that there may be differences in the properties of this enzyme
      related to tissue specific expression. In contrast to MTX, both Tomudex (Zeneca
      Pharmaceuticals, Wilmington, DE) and 1843U89, potent inhibitors of thymidylate
      synthetase, have low Kms for folylpolyglutamate synthetase, and polyglutamate
      forms of these inhibitors are accumulated to the same degree in both myeloid and
      lymphoid acute leukemia cells, paralleling the equivalent cytotoxicity found
      between myeloid and lymphoid leukemia cell lines. Based on these results, we
      believe a clinical trial of Tomudex in patients with acute myeloid leukemia is
      warranted.

PMID- 9242560
TI  - Human monocytes and neutrophils store transforming growth factor-alpha in a
      subpopulation of cytoplasmic granules.
AB  - Transforming growth factor-alpha (TGF-alpha) exerts several effects on target
      cells, such as neovascularization promotion and mitogenic signalling. Using
      immunoelectron microscopy, we show that monocytes and neutrophils, store TGF
      alpha in cytoplasmic granules. In monocytes, TGF-alpha did not colocalize with
      components of peroxidase-positive granules or with albumin of secretory vesicles.
      Furthermore, no colocalization of TGF-alpha with components of azurophilic or
      specific granules or secretory vesicles was observed in neutrophils. Activated
      monocytes and tissue-macrophages contained much less TGF-alpha-positive granules,
      suggesting TGF-alpha release. Western blot analysis showed a protein of 10 kD in
      lysates of monocytes. TGF-alpha mRNA was detected in monocytoid cells from the
      bone marrow by in situ hybridization. This study shows for the first time that
      monocytes and neutrophils contain TGF-alpha in all stages of maturation and that
      TGF-alpha in monocytes is stored in a large population of peroxidase-negative
      granules suggesting a function for these granules. Monocytes and neutrophils are
      important effector cells in inflammatory reactions. The present finding that
      these cells contain TGF-alpha might explain complications such as fibrosis and
      neoplastic transformation, caused by chronic inflammation.

PMID- 9242561
TI  - Fc gammaRII (CD32) is linked to apoptotic pathways in murine granulocyte
      precursors and mature eosinophils.
AB  - Murine granulocytes and precursors express low-affinity IgG Fc receptors (Fc
      gammaR). We investigated the effects of FcyR ligation on the development of
      eosinophils in cultures of normal murine bone marrow. Eosinophilopoiesis was
      induced by culture of bone marrow cells in the presence of cytokines (granulocyte
      macrophage colony-stimulating factor [GM-CSF], interleukin-3 [IL-3], and IL-5).
      Addition to the cultures of 2.4G2, a rat monoclonal antibody (mAb) that reacts
      with Fc gammaRII (CD32) and Fc gammaRIII (CD16), induced granulocyte apoptosis
      within 24 hours. Granulocytes in cultures that contained 2.4G2 showed chromatin
      condensation, binding of Annexin-V, and fas induction, and by electron
      microscopy, apoptosis was most commonly observed in cells of the eosinophil
      lineage. Since murine granulocytes can express both Fc gammaRII (CD32) and Fc
      gammaRIII (CD16), we investigated the effect of 2.4G2 on cultures of bone marrow
      obtained from Fc gammaRIII (CD16) gene-disrupted mice and found that the
      apoptosis induced with 2.4G2 was CD16-independent. Studies with bone marrow
      cultures from B6MLR-lpr/lpr and C3H/HEJ-gld/gld mice established that the Fc
      gammaRII (CD32)-triggered apoptosis was fas-fasL-dependent. When mature
      eosinophils isolated from hepatic granulomas of Schistosoma mansoni-infected mice
      were cultured in cytokines in the presence of 2.4G2, the eosinophils underwent
      apoptosis within 24 hours. These findings identify a previously unknown linkage
      between Fc gammaR on eosinophils and fas-mediated apoptosis, a connection that
      could be relevant to mechanisms by which eosinophils mediate tissue injury and
      antibody-dependent cellular cytotoxicity reactions.

PMID- 9242562
TI  - Mouse zeta- and alpha-globin genes: embryonic survival, alpha-thalassemia, and
      genetic background effects.
AB  - A classical notion regarding the expression of murine embryonic zeta- and adult
      alpha-globin genes holds that there is a switch in globin production from the
      embryonic to the adult form during fetal development. Our previous in situ
      hybridization studies challenged this view, since both zeta- and alpha-globin
      mRNAs can be detected simultaneously in the earliest erythrocyte populations.
      This finding raises the possibility that zeta-globin production might be wholly
      or partially redundant in embryos in which the adult alpha-globin is also
      expressed. To test this possibility, we created a null mutation of the zeta
      globin gene using homologous recombination in embryonic stem cells. Many outbred
      mice homozygous for the zeta-null mutation were able to develop normally,
      undermining the notion that there is an absolute need for zeta-globin and
      indicating that alpha-globin alone can serve the survival needs of the fetus.
      Interestingly, insertion of the PGK-Neo cassette (used to create the null
      mutation) into the zeta-globin gene appears to influence the expression of the
      nearby alpha-globin genes, giving rise to reduced alpha-globin production and to
      an alpha-thalassemia-like syndrome. There is also evidence indicating the strong
      influence of genetic background on the zeta-null and alpha1-null phenotypes, both
      of which are much more severe in the 129/SvEv inbred genetic background. These
      quantitative differences can potentially be exploited to identify genes important
      for erythropoiesis.

PMID- 9242563
TI  - Dietary magnesium supplementation ameliorates anemia in a mouse model of beta
      thalassemia.
AB  - To ascertain the quantitative effect on the disease beta-thalassemia of a low
      magnesium (Mg) diet compared with a high-Mg diet and a standard-Mg diet, we
      studied the effect these diets had over a 4-week period on beta-thalassemic (beta
      thal) mice compared with normal C57BL/6 mice used as controls. The low-Mg diet
      consisted of 6 +/- 2 mg Mg/kg body weight/d, the high-Mg diet 1,000 +/- 20 mg
      Mg/kg body weight/d, and the standard-Mg diet 400 +/- 20 mg Mg/kg body weight/d.
      Beta thal mice that were fed the low-Mg diet became more anemic, had reduced
      serum and erythrocyte Mg, and had decreased erythrocyte K. Their K-Cl cotransport
      increased, followed by commensurate cell dehydration. The high-Mg group showed a
      significant improvement of the anemia, increased serum and erythrocyte Mg,
      increased erythrocyte Mg, increased erythrocyte K, reduced K-Cl cotransport, and
      diminished cell dehydration. C57BL/6 control mice that received the low-Mg diet
      experienced anemia with erythrocyte dehydration, whereas the high-Mg diet had
      little effect on the hematologic parameters. Beta thal and C57BL/6 control mice
      that were fed a standard diet showed no changes. These results indicate that
      dietary Mg supplementation corrects hypomagnesemia and improves anemia in murine
      beta thal and should be assessed in human beta-thalassemia.

PMID- 9242564
TI  - A shortened life span of EKLF-/- adult erythrocytes, due to a deficiency of beta
      globin chains, is ameliorated by human gamma-globin chains.
AB  - Using homologous recombination, both EKLF alleles in murine embryonic stem (ES)
      cells were inactivated. These EKLF-/- ES cells were capable of undergoing in
      vitro differentiation to form definitive erythroid colonies that were similar in
      size and number to those formed by wild-type ES cells. However, the EKLF-/-
      colonies were poorly hemoglobinized and enucleated erythrocytes in these colonies
      contained numerous Heinz bodies. Reverse transcriptase-polymerase chain reaction
      (RT-PCR) analyses revealed that adult and embryonic globin genes were
      appropriately regulated, with the exception of beta h1-globin, which continued to
      be expressed at a very low level. The ratio of adult beta-globin/alpha-globin
      mRNA in the mutant ES cells was 1/15 of that in wild-type ES cells. When the EKLF
      /- cells were injected into blastocysts, they did not contribute at a detectable
      level to the mature erythrocyte compartment of the chimeric animals, based on
      analysis of glucose phosphate isomerase-1 (GPI-1) isozymes and hemoglobins that
      distinguish ES cell-derived erythrocytes from host blastocyst-derived
      erythrocytes. In contrast, semiquantitative RT-PCR analysis of RNA from
      reticulocytes of the same chimeric animals suggested that the ES cell-derived
      reticulocytes were present at a level of 6% to 8%. This indicated that the EKLF-/
      erythrocytes in adult animals must be short-lived, apparently due to the
      imbalance of beta-versus alpha-globin chains, leading to the precipitation of
      excess alpha-globin chains to form Heinz bodies. Consistent with this hypothesis,
      the short life span was ameliorated by introduction into the EKLF-/- ES cells of
      a human LCR/gamma-globin gene, as evidenced by the presence of ES cell-derived
      reticulocytes as well as mature erythrocytes in the blood of the chimeric
      animals.

PMID- 9242565
TI  - Ubiquitin aldehyde increases adenosine triphosphate-dependent proteolysis of
      hemoglobin alpha-subunits in beta-thalassemic hemolysates.
AB  - Two major causes of the anemia in beta-thalassemia are a deficiency in hemoglobin
      (Hb) beta-subunit (and consequently HbA) synthesis and, due to the resulting
      excess of Hb alpha-subunits, erythroid cell hemolysis. The hemolytic component
      might be ameliorated by increasing the intracellular proteolysis of the excess
      alpha-subunits. Isolated 3H-labeled alpha-chains are known to be degraded
      primarily by the adenosine triphosphate (ATP)- and ubiquitin (Ub)-dependent
      proteolysis pathway in unfractionated beta-thalassemic hemolysates. Our objective
      was to increase this degradation by targeted intervention. Ub aldehyde (Ubal), a
      synthetic inhibitor of isopeptidases (proteases that hydrolyze the bond between
      the Ub polypeptide and its protein adduct), was added to reaction mixtures
      containing a hemolysate from the blood cells of one of four beta-thalassemic
      donors and 3H-alpha-chains or 3H-alpha-globin as a substrate. Optimum enhancement
      of ATP-dependent degradation occurred at 0.4 to 1.5 micromol/L Ubal and ranged
      from 29% to 115% for 3H-alpha-chains and 47% to 96% for 3H-alpha-globin among the
      four hemolysates. We suggest that Ubal stimulates 3H-alpha-subunit proteolysis by
      inhibition of an isopeptidase(s) that deubiquitinates, or "edits," Ub-3H-alpha
      subunit conjugates, intermediates in the degradative pathway. In control studies,
      similarly low Ubal concentrations did not enhance the degradation of 3H
      alpha2beta2 (HbA) tetramers or inhibit the activities of methemoglobin reductase
      and four selected glycolysis pathway enzymes. These and other results may be the
      basis for a therapeutic approach to beta-thalassemia.

PMID- 9242566
TI  - Outbreak of hepatitis C virus infection in patients with hematologic disorders
      treated with intravenous immunoglobulins: different prognosis according to the
      immune status.
AB  - The influence of immunodeficiency on the course of hepatitis C virus (HCV)
      infection is still debated, although a worsening effect has been suggested. We
      compared the characteristics of hepatitis C in two groups of hematologic patients
      with different levels of immunocompetence who acquired the same virus strain
      after treatment with contaminated intravenous immunoglobulins (IVIG). Indications
      for IVIG therapy were idiopathic thrombocytopenic purpura (ITP) in six patients
      and hypogammaglobulinemia in 7 patients with various hematologic disorders, who
      were defined immunodeficient (ID). Infection rate was 100%. Five ID patients
      never developed HCV antibodies despite serum HCV-RNA positivity. The same HCV
      genotype was shown in 10 patients tested. Moreover, E1-E2 gene partial nucleotide
      sequencing, performed in four patients, showed identical or closely related amino
      acid sequences, thus strongly supporting the hypothesis of a common source of
      infection. Clinical acute infection did not differ significantly between the two
      groups, but subsequent liver failure developed in five of the seven ID patients
      and in none of the ITP patients (P = .04). Liver biopsy, performed in three
      cases, documented HCV as the only cause of liver damage. Six ID patients died,
      with liver disease being the primary cause of death in four cases and a
      contributory cause in two cases. Their median survival after IVIG was 12 months,
      significantly worse than that of ITP patients (P = .0028). We conclude that
      immunodeficiency markedly worsens the course of IVIG-acquired HCV infection in
      hematologic patients.

PMID- 9242567
TI  - Chronic hepatitis C virus infection after treatment for pediatric malignancy.
AB  - Sera of 658 patients who had completed treatment for pediatric malignancy were
      analyzed by a second-generation enzyme-linked immunosorbent assay and recombinant
      immunoblot assay test to assess the prevalence of hepatitis C virus (HCV)
      seropositivity. All HCV-seropositive patients underwent detailed clinical,
      laboratory, virologic, and histologic study to analyze the course of HCV
      infection. One hundred seventeen of the 658 patients (17.8%) were positive for
      HCV infection markers. Among the 117 anti-HCV+ patients, 41 (35%) were also
      positive for markers of hepatitis B virus infection with or without delta virus
      infection markers, 91 (77.8%) had previously received blood product transfusions,
      and 25 (21.4%) showed a normal alanine aminotransferase (ALT) level during the
      last 5-year follow-up (11 of them never had abnormal ALT levels). The remaining
      92 patients showed ALT levels higher than the upper limit of normal range. Eighty
      one of 117 (70%) anti-HCV+ patients were HCV-RNA+, with genotype 1b being present
      in most patients (54%). In univariate analysis, no risk factor for chronic liver
      disease was statistically significant. In this study, the prevalence of HCV
      infection was high in patients who were treated for a childhood malignancy. In
      about 20% of anti-HCV+ patients, routes other than blood transfusions are to be
      considered in the epidemiology of HCV infection. After a 14-year median follow
      up, chronic liver disease of anti-HCV+ positive patients did not show progression
      to liver failure.

PMID- 9242568
TI  - Autologous bone marrow transplantation for acute promyelocytic leukemia in second
      remission: prognostic relevance of pretransplant minimal residual disease
      assessment by reverse-transcription polymerase chain reaction of the PML/RAR
      alpha fusion gene.
AB  - Reverse-transcription polymerase chain reaction (RT-PCR) of the PML/RAR alpha
      fusion gene may predict relapse in acute promyelocytic leukemia (APL) patients in
      hematologic complete remission (CR). We have prospectively studied by RT-PCR 15
      PML/RAR alpha+ APL patients undergoing autologous bone marrow transplantation
      (ABMT) in second CR. The median time of first CR duration was 12 months (range, 6
      to 40). All patients were reinduced with all-trans retinoic acid (ATRA), followed
      in 12 of 15 cases by mitoxantrone and Ara-C as consolidation. Fourteen patients
      received the BAVC (BCNU, Ara-C, m-AMSA, and VP-16) schedule as conditioning
      regimen. Unpurged marrows were collected immediately before conditioning
      treatment, analyzed by RT-PCR, and reinfused at median of 2 months (range, 2 to
      7) from the achievement of second CR. Seven patients were PCR+ and eight PCR for
      PML/RAR alpha in their pretransplant marrows. All seven patients of the former
      group remained PCR+ during the follow-up and relapsed at a median time of 5
      months (range, 2 to 9) from ABMT and 9 months (range, 4 to 14) from second CR. Of
      the eight PCR- patients, all remained PCR- during the follow-up controls. One
      patient relapsed at 10 months from ABMT, one died of a secondary (PML/RAR alpha-)
      leukemia, and six are in hematologic and molecular remission at a median time of
      28 months (range, 15 to 60) after ABMT and 32 months (range, 17 to 62) from
      second CR. Our results indicate that, in APL patients in second CR, ABMT with
      PML/RAR alpha- marrow cells is likely to result in prolonged clinical and
      molecular remissions. Conversely, patients who test PCR+ after reinduction
      necessitate the use of alternative aggressive approaches, including unrelated
      allogeneic transplant.

PMID- 9242570
TI  - Does the adhesion molecule CD31 act as a minor histocompatibility antigen?

PMID- 9242569
TI  - Hepatitis C and G virus infection and liver dysfunction after allogeneic bone
      marrow transplantation: results from a prospective study.
AB  - Acute and chronic liver dysfunction is common after allogeneic bone marrow
      transplantation (BMT). Although toxicity, graft versus-host disease (GVHD), and
      viral infections are the major causes, etiologic diagnosis is difficult and often
      remains unknown. We conducted a prospective study to establish the role of the
      infection with both the hepatitis C virus (HCV) and the recently discovered
      hepatitis G virus (HGV) in liver dysfunction after BMT. From January 1994 to
      December 1995, 59 patients who had undergone an allogeneic BMT at our institution
      were enrolled in the study. HGV-RNA was identified in serum by nested polymerase
      chain reaction (PCR), and HCV was studied by the presence of second generation
      enzyme-linked immunosorbent assay (ELISA)-antibodies and HCV-RNA by nested PCR.
      HGV-RNA was detected in 25 patients (42%) (before BMT in 18 and after BMT in 7).
      HCV-RNA was present in 12 patients (20%) (before BMT in 11 and after BMT in one).
      The presence of HCV-RNA and HGV-RNA was clearly associated with a previous
      history of blood transfusions. No significant association was found between viral
      infection and acute liver toxicity. Some degree of liver dysfunction was present
      6 months after BMT in 25 of 40 evaluable patients (62%). Long-term liver
      dysfunction was more common among patients infected with HCV alone (3 of 4) or
      with both HCV and HGV (3 of 3) than in those infected with either HGV alone
      (eight of 13) or with no virus infection (10 of 20). We found a high prevalence
      of HGV infection in our BMT population. However, no role for HGV in liver disease
      could be established in this study, and the relationship between HGV infection
      and liver dysfunction requires further clarification.

PMID- 9242571
TI  - Serum transferrin receptor levels in different stages of iron deficiency.

PMID- 9242572
TI  - Antigen selection of multiple myeloma clonogenic B cells as evidenced by V(H) and
      V(L) gene mutations.

PMID- 9242573
TI  - Prevalence of hepatitis G virus in patients with aplastic anemia.

PMID- 9242574
TI  - AIDS-related extranodal non-Hodgkin's lymphomas with plasma cell differentiation.

PMID- 9242575
TI  - Role of mast cell and stem cell factor in hyperpigmented mycosis fungoides.

PMID- 9242577
TI  - Symposium on Biomedical Engineering: Novel Engineering Technology in Cryobiology
      Research and Its Applications

PMID- 9242578
TI  - Engineering-Based Contributions in Cryobiology
AB  - Over the past three decades there has been an increasing number of engineering
      trained researchers who have made the field of cryobiology a primary focus of
      their work. In prior times the advances in cryobiology were accomplished nearly
      exclusively by members of the life and medical science communities. In general,
      the practice of engineering may be distinguished by two features: an emphasis on
      rigorous quantitative measurement and analysis of processes and the synthesis of
      an understanding of fundamental principles of nature into the design of novel
      devices and processes for specific applications. One area of focus in cryobiology
      that engineers have emphasized is the design of new apparatus, including both
      experimental instrumentation and clinical diagnostic and therapeutic devices.
      There has been a broad spectrum of new apparatus invented to enable the
      quantitative control and measurement of the fundamental phenomena that govern
      processes in cryobiology. Among these are low-temperature cryomicroscopy stages
      and mass diffusion chambers, which now are often used in conjunction with digital
      image analysis algorithms to quantify changes to individual cells and tissues
      elicited during the process being studied. Other applications include the
      development of novel measurement techniques for assessing system properties and
      states during freezing and thawing. In cryosurgery and in cryopreservation new
      probes and apparatus have been designed to provide more accurate and effective
      processes to achieve clinical objectives. Equally important and complementary to
      the design of hardware is the development of analytical models which can be
      applied to understand and interpret experimental data and to predict the behavior
      of systems for operation in domains beyond those for which empirical data are
      available. Perhaps the most critical role of these models is for inverse solution
      techniques with experimental data to obtain values for the intrinsic constitutive
      properties of tissues which govern their response to freezing and thawing
      processes.

PMID- 9242579
TI  - Solidification Processes of Solutions
AB  - Recent progress in modeling pure liquid and dendritic alloy solidification is
      reviewed to lay the groundwork for freezing of solutions relevant to
      cryopreservation of biological materials. The classical Stefan problem of
      freezing/melting a pure substance is discussed first to introduce some of the
      fundamental concepts, and then the framework for modeling the freezing of
      solutions is reviewed. The formalism is extended to the freezing of a solution
      saturated porous media. As an application of the methodologies developed by
      engineers, freezing of a sodium chloride solution in a flat bag is simulated, and
      then using the temperature and salt concentration data calculated the kinetics of
      water loss from a model cell is predicted.

PMID- 9242581
TI  - Changing Times Require Changing Behavior

PMID- 9242582
TI  - Accumulation of manganese in rat brain following intranasal administration.
AB  - Manganese chloride (50-800 micrograms) was injected unilaterally into the right
      nostril of rats and its accumulation in the central nervous system (CNS) was
      monitored. Brain manganese levels were elevated in a dose-dependent, time
      dependent, and tissue-dependent manner. Elevated levels of manganese were
      detected in the right olfactory bulb and olfactory tubercle within 12 hr after
      instillation and remained elevated for at least 3 days. As little as 100
      micrograms of manganese chloride was sufficient to increase brain manganese
      levels. No changes were detected on the left side of the brain. The manganese
      content of the striatum, the target site for manganese neurotoxicity, was
      unchanged following acute administration, but was elevated when two injections
      were made 1 week apart. These results suggest that air-borne manganese can be
      retrogradely transported along olfactory neurons to the CNS and can reach deeper
      brain structures under appropriate exposure conditions.

PMID- 9242583
TI  - Differences in behavior among the chlorides of seven rare earth elements
      administered intravenously to rats.
AB  - Differences in behavior among the chlorides of seven rare earth elements (REEs)
      yttrium (Y), cerium (Ce), and praseodymium (Pr) (light REEs); europium (Eu) and
      dysprosium (Dy) (medium REEs); ytterbium (Yb) and lutetium (Lu) (heavy REEs)-were
      investigated through intravenous administration of the REEs to rats. (1)
      Distributions of REEs and mineral concentrations in the organs on Day 1 were
      investigated at low and high doses (9-10 and 18-20 mg REE/kg, or 56-66 and 112
      132 mumol REE/kg). More than 78% of the REEs administered was distributed into
      liver, bone, and spleen. High doses of Y, Eu, and Dy markedly increased the
      accumulation of REEs in spleen and lungs as well as the concentration of Ca in
      liver, spleen, and lungs. (2) The distribution patterns of REEs and changes in Ca
      concentrations in major organs over time were investigated by the administration
      of Pr, Eu, Dy, Yb (low dose), and Y (high dose). REEs disappeared from the blood
      within 1 day but were retained in the organs for a long time. The percentages of
      the doses of Y, Eu, Dy, and Yb found in the liver were highest at 8 hr to 2 days,
      then decreased gradually; hepatic Pr levels, however, remained high. Changes in
      Ca concentrations in liver, spleen, and lungs were in accordance with those of
      REEs. (3) Severe hepatotoxicity was observed after administration of Ce and Pr;
      fatty liver, jaundice, and elevated serum GOT and GPT levels were most prominent
      on Day 3. Therefore, we hypothesized that REE chlorides might be categorized into
      three groups according to their ionic radii (light REEs, Y and medium REEs, and
      heavy REEs) and from their behavior, i.e., distribution pattern, Ca-accumulating
      action, and hepatotoxicity.

PMID- 9242584
TI  - Cytochrome P450-mediated metabolism and nephrotoxicity of N-(3,5
      dichlorophenyl)succinimide in Fischer 344 rats.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is
      nephrotoxic in rats. Previous studies have suggested that oxidative hepatic
      biotransformation is required for the induction of kidney damage. The experiments
      described in this paper were designed to further investigate the relationship
      between NDPS metabolism and nephrotoxicity using various modulators of cytochrome
      P450 activity. Male Fischer 344 rats were pretreated with the P450 inducers
      Aroclor 1254 (ARO), isoniazid (INH), 3-methylcholanthrene (3-MC), and
      phenobarbital (PB), or the P450 inhibitor 1-aminobenzotriazole (ABT). Control
      animals received vehicle only. NDPS metabolism was investigated using hepatocytes
      isolated from the various treatment groups. Separate experiments were also
      conducted to evaluate the effects of these pretreatments on NDPS-induced
      nephrotoxicity in rats. PB and ARO enhanced formation of the known nephrotoxic
      NDPS metabolites, N-(3,5-dichlorophenyl)-2-hydroxysuccinimide, N-(3,5
      dichlorophenyl)-2-hydroxysuccinamic acid, and N-(3,5-dichlorophenyl)-3
      hydroxysuccinamic acid, by the hepatocytes. In contrast, ABT inhibited formation
      of the nephrotoxic metabolites, whereas INH and 3-MC did not alter NDPS
      biotransformation. NDPS-induced renal damage was potentiated by pretreating the
      rats with PB or ARO and was attenuated by ABT. Compared with control animals,
      toxicity was unaffected by INH or 3-MC pretreatments. Thus, there was a
      correlation between pretreatments that induce P450-mediated NDPS metabolism and
      the effects that these compounds have on NDPS-induced nephrotoxicity. The data
      indicate that specific P450 isozymes metabolize NDPS to its hydroxylated products
      and suggest that these metabolites mediate the nephrotoxicity induced by NDPS.

PMID- 9242585
TI  - Trichloroethylene-induced mouse lung tumors: studies of the mode of action and
      comparisons between species.
AB  - CD-1 mice exposed to 450 ppm trichloroethylene, 6 hr/day, 5 days/week, for 2
      weeks showed a marked vacuolation of lung Clara cells after the first exposure of
      each week and a marked increase in cell division after the last exposure of each
      week. The damage seen in mouse lung Clara cells is caused by an accumulation of
      chloral resulting from high rates of metabolism of trichloroethylene but poor
      clearance of chloral to trichloroethanol and its glucuronide. The activity and
      distribution of the key metabolizing enzymes in this pathway have been compared
      in mouse, rat, and human lung. While mouse lung microsomal fractions were able to
      metabolize trichloroethylene to chloral at significant rates, the rate in rat
      lung was 23-fold lower and a rate could not be detected in human lung microsomes
      at all. Immunolocalization of cytochrome P450IIE1 in lung sections revealed high
      concentrations in mouse lung Clara cells with lesser amounts in type II cells.
      Lower levels of enzyme could be detected in Clara cells of rat lung, but not at
      all in human lung sections. Western blots of lung tissues from the three species
      and of mouse lung Clara cells were entirely consistent with these observations.
      Consequently, it is highly unlikely that humans exposed to trichloroethylene are
      at risk from the lung damage/cell proliferation mechanism that is believed to
      lead to the development of tumors in the mouse lung.

PMID- 9242586
TI  - Effect of methimazole, an FMO substrate and competitive inhibitor, on the
      neurotoxicity of 3,3'-iminodipropionitrile in male rats.
AB  - This study was designed to examine the role of flavin-containing monooxygenase
      (FMO) on the auditory and vestibular neurotoxicity of 3,3'-iminodipropionitrile
      (IDPN) using the FMO substrate and competitive inhibitor methimazole (MMI).
      Specifically, the purpose was to block the FMO-mediated conversion of IDPN to the
      putative neurotoxic metabolite N-hydroxy3,3'-iminodipropionitrile (HOIDPN). In
      three separate experiments, adult male Long-Evans hooded rats were administered
      (ip) saline (vehicle), MMI, IDPN, or HOIDPN individually, or a combination of
      IDPN and MMI or HOIDPN and MMI. Animals were observed daily for signs of the ECC
      syndrome (excitation with choreiform and circling movements) for 10 days. One to
      2 weeks after exposure, a battery of behavioral tests was used to examine
      vestibular and auditory function. MMI completely blocked the neurotoxicity
      associated with a 600 mg/kg dose of IDPN and partially blocked the effects of a
      1000 mg/kg dose of IDPN. In contrast, MMI failed to block, and instead increased,
      the neurotoxicity associated with HOIDPN. These data suggest that FMO-mediated
      metabolism of IDPN is necessary for the generation of a metabolite responsible
      for the vestibular and auditory neurotoxicities.

PMID- 9242587
TI  - Opposite effects of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8
      tetrachlorodibenzo-p-dioxin on the antibody response to sheep erythrocytes in
      mice.
AB  - The effect that cotreatment with 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has on the antibody plaque-forming
      cell (PFC) response to sheep red blood cells (SRBCs) was determined in female
      B6C3F1 mice. Groups of eight mice per group were given a single oral dose of
      PCB153 alone (0, 3.58, 35.8, or 358 mg/kg), TCDD alone (0, 0.1, 1, or 10
      micrograms/kg), and all possible combinations of these doses in corn oil 7 days
      prior to immunization with SRBCs. Separate groups of mice were given
      phenobarbital (PB) parenterally by intraperitoneal injection at a dosage of 160
      mg/kg/day for 3 days. Four days after intravenous immunization, body, spleen,
      thymus, and liver weights and the PFC response to SRBCs were determined. Exposure
      to TCDD alone resulted in a dose-related suppression of the PFC response, with
      significant suppression at 1 and 10 micrograms/kg. In contrast, exposure to
      PCB153 alone resulted in the enhancement of the PFC response at 358 mg/kg.
      Combined exposure to 358 mg/ kg PCB153 and TCDD resulted in no change (PCB153 +
      0.1 microgram/ kg TCDD) or suppression (PCB153 + 1 or 10 micrograms/kg TCDD) of
      the PFC response relative to PCB153 alone; however, the PFC response was enhanced
      (PCB153 + 0.1 microgram/kg TCDD), unaffected (PCB153 + 1 microgram/kg TCDD), or
      suppressed (PCB153 + 10 micrograms/kg TCDD) relative to corn oil controls. PB did
      not affect the PFC response to SRBCs, despite a 13-fold induction of hepatic
      pentoxyresorufin O-dealkylase (PROD) activity. These results suggest that PCB153
      enhancement of the PFC response is not related to PROD induction and that it acts
      as a functional antagonist rather than an aryl hydrocarbon receptor or
      dispositional antagonist. By enhancing the PFC response to SRBCs, PCB153 raises
      the "setpoint" response level. Consequently, cotreatment with an
      immunosuppressive dose of TCDD fails to suppress the PFC response relative to
      corn oil controls, while clearly suppressing it relative to the appropriate
      control, PCB153 alone.

PMID- 9242588
TI  - The effects of the phosphorothioate insecticide fenitrothion on mammalian
      cytochrome P450-dependent metabolism of estradiol.
AB  - Phosphorothioate insecticides, such as fenitrothion, are suicide substrates of
      cytochromes P450 (P450). These compounds undergo oxidative desulfuration by P450
      resulting in the release and subsequent binding of atomic sulfur to the enzyme.
      Consequently, the P450-dependent metabolism of certain endogenous substrates
      could be inhibited by exposure to these insecticides. Formation of 2
      hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2), 16 alpha-hydroxyestrone
      (16 alpha-OHE1), and estriol in mammals occurs by P450-dependent hydroxylation of
      estradiol at various positions on the steroid nucleus. In the present study,
      pretreatment of male Swiss Webster mice with increasing doses of fenitrothion
      resulted in dose-dependent biphasic decreases in 2-OHE2 and 4-OHE2 production in
      mouse hepatic microsomes compared to control, with substantial decreases even at
      a dosage as low as 7 mg/kg. Fenitrothion pretreatment also resulted in dose
      dependent biphasic increases in 16 alpha-OHE1 and estriol production, along with
      substantial increases in estrone formation, probably as a result of shunting from
      the inhibition of 2- and 4-hydroxylation. These data suggest that exposure to
      fenitrothion might alter estradiol metabolism by inhibition of certain P450
      isozymes.

PMID- 9242589
TI  - Role of testis exposure levels in the insensitivity of prepubertal rats to
      carbendazim-induced testicular toxicity.
AB  - Our recent studies have indicated that benomyl (BNL)-induced testicular toxicity
      is mediated by its major metabolite carbendazim (CBZ). The present study has used
      CBZ to investigate hypotheses that could explain prepubertal insensitivity to
      BNL. When CBZ (164 mg/kg intraperitoneally) was administered to postpubertal and
      prepubertal rats, it caused little testicular damage in prepubertal rats, but in
      adult rats, sloughing of the seminiferous epithelium resulted. When the
      inhibitory effect of CBZ on prepubertal testicular microtubule assembly was
      compared with that on postpubertal assembly, the IC50 values were very similar.
      Pharmacokinetic studies revealed that blood levels of CBZ were comparable in the
      two age groups; however, higher levels of CBZ were found in the adult testes
      (210.52 nmol/g wet wt) in comparison with young testes (67.77 nmol/g wet wt).
      These data suggest that delivery to and/or retention of CBZ in the testis may
      play a role in the age-dependent differences in susceptibility to CBZ toxicity.
      When CBZ was administered intratesticularly to reach levels sufficient to cause
      damage, the young animals did show an increased incidence of vacuolization and
      detachment of the seminiferous epithelium; however, in contrast to the older
      animals, sloughing of the seminiferous epithelium was not observed in the
      prepubertal animals. Overall, the low levels of CBZ measured in the testes of
      prepubertal animals offer a partial explanation for the insensitivity of young
      animals to CBZ-induced testicular toxicity following intraperitoneal
      administration. A differential responsiveness between the two age groups is also
      likely, however, since prepubertal animals lack elongated spermatids and it is
      sloughing of this cell type that characterizes CBZ-induced testicular toxicity in
      the adult.

PMID- 9242590
TI  - Dichloromethane metabolism to formaldehyde and reaction of formaldehyde with
      nucleic acids in hepatocytes of rodents and humans with and without glutathione S
      transferase T1 and M1 genes.
AB  - Metabolism of dichloromethane (DCM) to formaldehyde (HCHO) via a glutathione S
      transferase (GST) pathway is thought to be required for its carcinogenic effects
      in B6C3F1 mice. In humans, this reaction is catalyzed primarily by the protein
      product of the gene GSTT1, a member of the Theta class of GST, and perhaps to a
      small extent by the protein product of the gene GSTM1. Humans are polymorphic
      with respect to both genes. Since HCHO may bind to both DNA and RNA forming DNA
      protein crosslinks (DPX) and RNA-formaldehyde adducts (RFA), respectively, these
      products were determined in isolated hepatocytes from B6C3F1 mice, F344 rats,
      Syrian golden hamsters, and humans to compare species with respect to the
      production of HCHO from DCM and its reaction with nucleic acids. Only mouse
      hepatocytes formed detectable amounts of DPX, the quantities of which
      corresponded well with quantities of DPX formed in the livers of mice exposed to
      DCM in vivo [Casanova, M., Conolly, R.B., and Heck, H. d'A. (1996). Fundam. Appl.
      Toxicol. 31, 103-116]. Hepatocytes from all rodent species and from humans with
      functional GSTT1 and GSTM1 genes formed RFA. No RFA were detected in human cells
      lacking these genes. Yields of RFA in hepatocytes of mice were 4-fold higher than
      in those of rats, 7-fold higher than in those of humans, and 14-fold higher than
      in those of hamsters. The RFA:DPX ratio in mouse hepatocytes incubated with DCM
      was approximately 9.0 +/- 1.4, but it was 1.1 +/- 0.3 when HCHO was added
      directly to the medium, indicating that HCHO generated internally from DCM is not
      equivalent to that added externally to cells and that it may occupy separate
      pools. DPX were not detected in human hepatocytes even at concentrations
      equivalent to an in vivo exposure of 10,000 ppm; however, the possibility that
      very small amounts of DPX were produced from DCM cannot be excluded, since HCHO
      was formed in human cells. Maximal amounts of DPXliver that might be formed in
      humans were predicted from the amounts in mice and the relative amounts of RFA in
      hepatocytes of both species. With predicted DPXliver as the dosimeter, the unit
      risk, the upper 95% confidence limit on the cancer risk, and the margin of
      exposure were calculated at several concentrations using the linearized
      multistage and benchmark dose methods. Since the actual delivered dose is smaller
      than that predicted, the results suggest that DCM poses at most a very low risk
      of liver cancer to humans.

PMID- 9242591
TI  - A rapid in vitro assay for evaluation of metabolism-dependent cytotoxicity of
      antiepileptic drugs on isolated human lymphocytes.
AB  - In vitro assessment of human lymphocyte viability by trypan blue dye exclusion in
      the presence of an external metabolizing system (microsomes plus NADPH) has been
      shown to be a useful method in assessing predisposition to idiopathic toxicity in
      response to various anticonvulsant drugs. The trypan blue method, however, is
      labor intensive, is time consuming, is prone to human error, is not suitable for
      high-volume toxicity screening, and excludes autolysed cells. The objective of
      this study was to develop a rapid, high-capacity, objective, and easy in vitro
      cytotoxicity method for the detection of metabolism-dependent cytotoxicity of a
      test chemical. The in vitro system uses an external metabolizing system (rabbit
      microsomes) in conjunction with isolated human lymphocytes as the target cells.
      Cellular toxicity was determined by assessing plasma membrane integrity using a
      membrane-impermeant fluorescent nucleic acid dye (YO-PRO-1) and a multiwell plate
      scanner for fluorescence. Using this system, cells incubated with either
      acetaminophen (1500 micrograms/ml), carbamazepine (62.5 microM), phenytoin (62.5
      microM), or phenobarbital (62.5 microM) showed net increases in percentage cell
      death of 31 +/- 5, 11 +/- 4, 0 +/- 3, and 2 +/- 3, respectively. A metabolism
      dependent concentration-response was observed for valproic acid-induced
      cytotoxicity, which approached a plateau at a concentration of 4000 micrograms/ml
      with a net percentage cell death of 31 +/- 4. This technique resolves various
      technical difficulties inherent in viability determinations by the trypan blue
      exclusion method. The YO-PRO-1 method also may be useful in a clinical setting
      for the assessment of patients with a genetically determined susceptibility to
      certain drugs and for identifying the responsible drug in patients with
      idiopathic toxicity undergoing multiple-drug therapy.

PMID- 9242592
TI  - Taxonomic status and phylogenetic relationships of some species of the genus
      Gammarus (Crustacea, Amphipoda) deduced from mitochondrial DNA sequences.
AB  - Mitochondrial DNA nucleotide sequence analysis was used to determine the extent
      of genetic differentiation among six species of the genus Gammarus (Crustacea,
      Amphipoda) common in France (G. fossarum, G. pulex, G. lacustris, G. wautieri, G.
      roeseli, G. marinus). From 23 different populations, 104 specimens were compared
      to examine their taxonomic status and their phylogenetic relationships.
      Nucleotide sequences for a 376-base segment of the cytochrome c oxidase subunit I
      (COI) gene were obtained through direct sequencing of amplified DNA. The strong
      sequence variability found at the interspecific level, generally masked by
      morphological or ecological similarities, is consistent with that observed for
      other crustaceans and supports existing species classifications. A high level of
      genetic variation was observed at the intraspecific level, suggesting that the
      COI gene will be a powerful marker for amphipod population biology. Based on the
      mitochondrial population biology. Based on the mitochondrial DNA results, we
      propose a phylogenetic hypothesis of the relationships among the six studied
      species, which is discussed in biogeographic and evolutionary terms.

PMID- 9242593
TI  - Cladistic analysis of Tospovirus using molecular characters.
AB  - The genus Tospovirus was thought to be composed only of the tomato spotted wilt
      virus (TSWV), but now at least four Tospovirus species have been proposed based
      on serological and molecular data. A classification of tospoviruses has been
      proposed taking into account global similarities of the N gene and N protein
      sequences of 7 isolates of Tospovirus. Because phylogenetic analyses based on
      global similarities can lead to classifications which do not mirror the genealogy
      of the group, we have employed a cladistic analysis using parsimony of this genus
      with RNA sequences of 450 nucleotides of the N gene from 14 new Argentinean
      isolates and 4 previously described isolates. Representatives of the Bunyaviridae
      family, Rift Valley Fever Virus (Phlebovirus) and Bunyamwera (Bunyavirus), were
      used as the outgroup in separate analyses.

PMID- 9242594
TI  - Hadamard conjugations and modeling sequence evolution with unequal rates across
      sites.
AB  - This paper considers the many different distributions that may approximate the
      distribution of site rates in DNA sequences and shows how the Hadamard
      conjugation may be modified to take these into account. This is done for both 2
      state and 4-state data. Distributions which give simple closed forms include the
      gamma (gamma) distribution, the inverse Gaussian distribution (which is similar
      to the lognormal), and a mixture of either of these with a proportion of sites
      which cannot change (invariant sites). It is seen that the tail of a distribution
      can have major effects upon the coefficient of variation of site rates. Because
      the Hadamard conjugation can be used to either correct data or predict the data
      given the model (i.e., the likelihood of site patterns), light is shed on
      properties of maximum likelihood tree selection with unequal site rates. Analysis
      of rRNA shows how unequal rates across sites can change the optimal tree. Maximum
      likelihood analysis also shows that distinct distributions fit each data set,
      with the gamma often not being the best. Analyzing both these data and a long
      stretch of primate mtDNA reveals evidence of many "hidden" multiple
      substitutions, while signals not corresponding to the preferred biological tree
      generally decrease an unequal rates are allowed for. Last, we discuss the
      expected behavior of sequences evolving by models where stabilizing selection
      alone explains unequal site rates. Such models do not explain "synapomorphies" or
      informative changes in ancient molecules, because while stabilizing selection can
      vastly decrease change at a site, it will also vastly accelerate back
      substitution (leaving only a covarion model to explain old synapomorphies). When
      and why models allowing a continuous distribution of site rates (e.g., gamma)
      will approximate covarion evolution requires further study.

PMID- 9242595
TI  - Evolution and selection of primate T cell antigen receptor BV8 gene subfamily.
AB  - The set of potential T cell receptor specificities is highly diverse. The
      relative contributions of T cell receptor (TCR) V beta gene segment
      polymorphisms, duplications, deletions, and gene conversions to this final T cell
      receptor protein diversity are unknown. To study these mechanisms, we sequenced
      and compared closely related primate TCR gene segments from BV8S1, S2, and S5.
      Interspecies comparisons show that these gene segments have sustained multiple
      duplication, gene conversion, and deletion events during the last 35 million
      years of anthropoid primate evolution. BV8 coding sequences are generally
      conserved with respect to their flanking noncoding sequences, but we find no
      evidence for positive or negative selection in sequences coding for the first two
      putative complementarity-determining (ligand-binding) regions. Sequences of
      TCRBV8 gene segments from unrelated humans demonstrate no nonsynonymous
      substitutions in nonleader regions of either the BV8S1 or S2 gene segments. We
      conclude that gene duplication, deletion, and conversion mechanism contribute in
      a substantial way to the overall diversity of the TCRBV8 gene segment repertoire
      in primate evolution and that germline substitutions and consequent polymorphisms
      in CDRs 1 and 2 of these gene segments probably do not play an active role in
      generating TCR beta chain protein variation.

PMID- 9242596
TI  - Phylogenetic relationships in the Papilionoideae (family Leguminosae) based on
      nucleotide sequences of cpDNA (rbcL) and ncDNA (ITS 1 and 2).
AB  - Sequences of cpDNA (rbcL) were determined for 94 species and of ncDNA [ITS 1 + 2
      regions (internal transcribed spacer) of rDNA] for 75 species representing mainly
      the papilionoid tribes Sophoreae, Thermopsideae Podalyrieae, Liparieae,
      Crotalarieae, and Genisteae. Sequence data were used to reconstruct the
      underlying molecular phylogeny. Several clusters and furcations were identical in
      the rbcL and ITS trees of the Papilionoideae, indicating that a reticulate
      evolution due to past hybridization of members from different tribes and genera
      is unlikely: The Sophoreae (especially Styphnolobium japonicum (syn. Sophora
      japonica) and Sophora secundiflora) are positioned at the base of the papilionoid
      tree, whereas some other Sophora species (Sophora davidii, flavescens, jaubertii,
      microphylla) are closely related to Thermopsideae/Podalyrieae. The
      Thermopsideae/Podylyrieae cluster (including Liparieae) shares ancestry with the
      Crotalarieae and Genisteae. Argyrolobium (African taxa) and Melolobium cluster
      between Crotalarieae and Genisteae. In the Genisteae three clusters are apparent:
      the monophyletic genus Lupinus, the Cytisus-, and the Genista-group. According to
      this analysis, the Cytisus-complex includes Cytisus, Lembotropis, Chamaecytisus,
      Spartocytisus, and Calicotome. The Genista-group consists of Genista, Teline, and
      Chamaespartium sagittale. Other genera (e.g., Adenocarpus, Argyrocytisus,
      Cytisophyllum, Erinacea, Laburnum, Petteria, Retama, Spartium, and Ulex) could
      not be attributed unequivocally to the Cytisus or Genista complex.

PMID- 9242597
TI  - The phylogeny of the Caelifera (Insecta, Orthoptera) as deduced from mtrRNA gene
      sequences.
AB  - Fragments of both mitochondrial ribosomal RNA genes of 32 caeliferan taxa
      (representing six of the seven superfamilies) and six outgroup Orthopteroids were
      sequenced. The combined alignment length was 630 bp after removal of all
      ambiguously aligned positions. Separation for the basal taxa was problematic and
      analysis using the LogDet transformation indicated that shared base composition
      biases were a confounding factor. The suborder Caelifera and all traditional
      caeliferan superfamilies except the Pamphagoidea are retrieved as monophyletic
      groups, though the Eumastacoidea lack significant bootstrap support. Of the
      traditional pamphagoid taxa, the Pamphagidae is embedded between classically
      acridid subfamilies, whereas Pyrgomorphidae is placed close to the Pneumoroidea.
      The morphological similarities of the Pyrgomorphidae and Pamphagidae may thus be
      homoplasic. A consensus tree based on five different methods of analysis
      indicated the following order: (Tridactyloidea, Tetrigoidea (Eumastacidae,
      Proscopiidae (Pneumoridae, Pyrgomorphidae (Acrididae + Pamphagidae)))).

PMID- 9242598
TI  - Phylogeny of the side-blotched lizards (Phrynosomatidae:Uta) based on mtDNA
      sequences: support for midpeninsular seaway in Baja California.
AB  - We investigated the phylogenetic relationships of western North American Side
      blotched lizards, genus Uta, using mitochondrial DNA partial gene sequences from
      cytochorme b and ATPase 6. Uta stejnegeri appeared basal in our tree followed by
      U. palmeri. Uta stansburiana from the islands of Angel de la Guarda, Mejia, and
      Raza formed the next clade, followed by U. antiqua and other populations of U.
      stansburiana. These relationships suggest that the populations on the Angel de la
      Guarda island block should be recognized as a distinct species. Remaining
      populations of U. stansburiana formed two clades, corresponding to the northern
      and southern Baja California peninsula. Uta stellata and U. squamata occurred
      within the northern and southern clades, respectively. The discontinuity requires
      a long-lasting isolation, the only reasonable explanation being a former
      midpeninsular seaway. Correlations between our cladogram and magnetic anomalies
      in the Gulf of California date formation of the seaway at 1 million years ago.

PMID- 9242599
TI  - Re: Phylogenetic relationships of the Canary Islands endemic lizard genus
      Gallotia inferred from mitochondrial DNA sequences: incorporation of a new
      subspecies.

PMID- 9242607
TI  - Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized
      by the widespread development of distinctive tumors termed hamartomas. TSC
      determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2).
      The TSC1 gene was identified from a 900-kilobase region containing at least 30
      genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein
      of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of
      unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of
      which were truncating, and a single mutation (2105delAAAG) was seen in six
      apparently unrelated patients. In one of these six, a somatic mutation in the
      wild-type allele was found in a TSC-associated renal carcinoma, which suggests
      that hamartin acts as a tumor suppressor.

PMID- 9242608
TI  - Mitochondrial and chloroplast phage-type RNA polymerases in Arabidopsis.
AB  - In addition to the RNA polymerases (RNAPs) transcribing the nuclear genes,
      eukaryotic cells also require RNAPs to transcribe the genes of the mitochondrial
      genome and, in plants, of the chloroplast genome. The plant Arabidopsis thaliana
      was found to contain two nuclear genes similar to genes encoding the
      mitochondrial RNAP from yeast and RNAPs of bacteriophages T7, T3, and SP6. The
      putative transit peptides of the two polymerases were capable of targeting fusion
      proteins to mitochondria and chloroplasts, respectively, in vitro. The results
      indicate that the mitochondrial RNAP in plants is a bacteriophage-type enzyme. A
      gene duplication event may have generated the second RNAP, which along with the
      plastid-encoded eubacteria-like RNAP could transcribe the chloroplast genome.

PMID- 9242609
TI  - Sensitization to morphine induced by viral-mediated gene transfer.
AB  - Repeated administration of morphine sensitizes animals to the stimulant and
      rewarding properties of the drug. It also selectively increases expression of
      GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area, a
      midbrain region implicated in morphine action. By viral-mediated gene transfer, a
      causal relation is shown between these behavioral and biochemical adaptations:
      Morphine's stimulant and rewarding properties are intensified after
      microinjections of a viral vector expressing GluR1 into the ventral tegmental
      area. These results confirm the importance of AMPA receptors in morphine action
      and demonstrate specific locomotor and motivational adaptations resulting from
      altered expression of a single localized gene product.

PMID- 9242610
TI  - An antagonist decoy receptor and a death domain-containing receptor for TRAIL.
AB  - TRAIL, also called Apo2L, is a cytotoxic protein that induces apoptosis of many
      transformed cell lines but not of normal tissues, even though its death domain
      containing receptor, DR4, is expressed on both cell types. An antagonist decoy
      receptor (designated as TRID for TRAIL receptor without an intracellular domain)
      that may explain the resistant phenotype of normal tissues was identified. TRID
      is a distinct gene product with an extracellular TRAIL-binding domain and a
      transmembrane domain but no intracellular signaling domain. TRID transcripts were
      detected in many normal human tissues but not in most cancer cell lines examined.
      Ectopic expression of TRID protected mammalian cells from TRAIL-induced
      apoptosis, which is consistent with a protective role. Another death domain
      containing receptor for TRAIL (designated as death receptor-5), which
      preferentially engaged a FLICE (caspase-8)-related death protease, was also
      identified.

PMID- 9242612
TI  - Neural correlates of motor memory consolidation.
AB  - Computational studies suggest that acquisition of a motor skill involves learning
      an internal model of the dynamics of the task, which enables the brain to predict
      and compensate for mechanical behavior. During the hours that follow completion
      of practice, representation of the internal model gradually changes, becoming
      less fragile with respect to behavioral interference. Here, functional imaging of
      the brain demonstrates that within 6 hours after completion of practice, while
      performance remains unchanged, the brain engages new regions to perform the task;
      there is a shift from prefrontal regions of the cortex to the premotor, posterior
      parietal, and cerebellar cortex structures. This shift is specific to recall of
      an established motor skill and suggests that with the passage of time, there is a
      change in the neural representation of the internal model and that this change
      may underlie its increased functional stability.

PMID- 9242611
TI  - Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors.
AB  - TRAIL (also called Apo2L) belongs to the tumor necrosis factor family, activates
      rapid apoptosis in tumor cells, and binds to the death-signaling receptor DR4.
      Two additional TRAIL receptors were identified. The receptor designated death
      receptor 5 (DR5) contained a cytoplasmic death domain and induced apoptosis much
      like DR4. The receptor designated decoy receptor 1 (DcR1) displayed properties of
      a glycophospholipid-anchored cell surface protein. DcR1 acted as a decoy receptor
      that inhibited TRAIL signaling. Thus, a cell surface mechanism exists for the
      regulation of cellular responsiveness to pro-apoptotic stimuli.

PMID- 9242613
TI  - Drosophila mitotic domain boundaries as cell fate boundaries.
AB  - Fate determination in Drosophila embryos is evidenced by the appearance of
      mitotic domains. To identify fate or fates of cells, individual cells in mitotic
      domains 2, 8, and 15 were marked and monitored through development. Comparison of
      the different fates indicated that domain boundaries are cell fate boundaries.
      Cells were marked by expression of GAL4-dependent transgenes after
      photoactivation of a caged GAL4VP16 analog that had its DNA binding activity
      inhibited with a photolabile blocking reagent. Caged GAL4VP16 was also used to
      induce gene expression in Xenopus embryos. Thus, photoactivated gene expression
      is a versatile tool for spatiotemporal control of gene expression.

PMID- 9242614
TI  - The influence of dominance rank on the reproductive success of female
      chimpanzees.
AB  - Female chimpanzees often forage alone and do not display obvious linear dominance
      hierarchies; consequently, it has been suggested that dominance is not of great
      importance to them. However, with the use of data from a 35-year field study of
      chimpanzees, high-ranking females were shown to have significantly higher infant
      survival, faster maturing daughters, and more rapid production of young. Given
      the foraging behavior of chimpanzees, high rank probably influences reproductive
      success by helping females establish and maintain access to good foraging areas
      rather than by sparing them stress from aggression.

PMID- 9242616
TI  - Natural behavior polymorphism due to a cGMP-dependent protein kinase of
      Drosophila.
AB  - Naturally occuring polymorphisms in behavior are difficult to map genetically and
      thus are refractory to molecular characterization. An exception is the foraging
      gene (for), a gene that has two naturally occurring variants in Drosophila
      melanogaster food-search behavior: rover and sitter. Molecular mapping placed for
      mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)
      dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and
      transgenic sitters expressing a dg2 complementary DNA from rover showed
      transformation of behavior to rover. Thus, PKG levels affected food-search
      behavior, and natural variation in PKG activity accounted for a behavioral
      polymorphism.

PMID- 9242615
TI  - Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid
      human fibroblasts.
AB  - Most somatic cells die after a finite number of cell divisions, a phenomenon
      described as senescence. The p21(CIP1/WAF1) gene encodes an inhibitor of cyclin
      dependent kinases. Inactivation of p21 by two sequential rounds of targeted
      homologous recombination was sufficient to bypass senescence in normal diploid
      human fibroblasts. At the checkpoint between the prereplicative phase of growth
      and the phase of chromosome replication, cells lacking p21 failed to arrest the
      cell cycle in response to DNA damage, but their apoptotic response and genomic
      stability were unaltered. These results establish the feasibility of using gene
      targeting for genetic studies of normal human cells.

PMID- 9242617
TI  - Conformational changes at the nucleotide binding of GroEL induced by binding of
      protein substrates. Luminescence studies.
AB  - 2'-Deoxy-3'-anthraniloyl adenosine-5-triphosphate (ANT-dATP) coordinated to Tb3+
      was used as an environmentally sensitive probe of the nucleotide-binding site of
      GroEL. Tb3+.ANT-dATP recognizes the nucleotide-binding site of GroEL and inhibits
      ATPase activity. Sensitized luminescence, arising from resonance energy transfer
      from the anthraniloyl moiety to Tb3+, is substantially enhanced in the presence
      of GroEL. Binding of denatured mitochondrial malate dehydrogenase to the apical
      domain of GroEL causes a red shift in the fluorescence emitted by anthraniloyl
      and further enhancement in the phosphorescence emitted by Tb3+ upon excitation at
      320 nm. It is suggested that binding of the protein substrate initiates domain
      movement, which is extended to the nucleotide-binding site. The luminescence
      results are discussed in reference to the structure of GroEL derived from x-ray
      crystallographic studies.

PMID- 9242618
TI  - Selective loss of fibrinogen clotting in a loop-less thrombin.
AB  - The autolysis loop of thrombin comprises nine residues, from Glu146 to Lys149e,
      five of which (Ala149a-Lys149e) are inserted relative to trypsin and
      chymotrypsin. Deletion of the insertion Ala149a-Lys149e causes no significant
      change in the properties of the enzyme, except for a slight enhancement of
      protein C activation. Deletion of the entire Glu146-Lys149e loop, however,
      reduces fibrinogen clotting 240-fold, but decreases protein C activation only 2
      fold. This loop-less mutant is de facto an exclusive activator of protein C,
      having lost the primary procoagulant function of thrombin. Because the autolysis
      loop affects fibrinogen binding, but not protein C activation, it provides a
      target for new drugs designed to suppress exclusively the procoagulant activity
      of thrombin.

PMID- 9242619
TI  - Heparin-dependent modification of the reactive center arginine of antithrombin
      and consequent increase in heparin binding affinity.
AB  - Antithrombin, the principal plasma inhibitor of coagulation proteinases,
      circulates in a form with low inhibitory activity due to partial insertion of its
      reactive site loop into the A-beta-sheet of the molecule. Recent crystallographic
      structures reveal the structural changes that occur when antithrombin is
      activated by the heparin pentasaccharide, with the exception of the final
      changes, which take place at the reactive center itself. Here we show that the
      side chain of the P1 Arg of alpha-antithrombin is only accessible to modification
      by the enzyme peptidylarginine deiminase on addition of the heparin
      pentasaccharide, thereby inactivating the inhibitor, whereas the natural P1 His
      variant, antithrombin Glasgow, is unaffected, indicating that only the P1 Arg
      becomes accessible. Furthermore, the deimination of P1 Arg converts antithrombin
      to a form with 4-fold higher affinity for the heparin pentasaccharide, similar to
      the affinity found for the P1 His variant, due to a lowered dissociation rate
      constant for the antithrombin-pentasaccharide complex. The results support the
      proposal that antithrombin circulates in a constrained conformation, which when
      released, in this study by perturbation of the bonding of P1 Arg to the body of
      the molecule, allows the reactive site loop to take up the active inhibitory
      conformation with exposure of the P1 Arg.

PMID- 9242620
TI  - Novel tetrasaccharides isolated from squid cartilage chondroitin sulfate E
      contain unusual sulfated disaccharide units GlcA(3-O-sulfate)beta1-3GalNAc(6-O
      sulfate) or GlcA(3-O-sulfate)beta1-3GalNAc.
AB  - We previously isolated novel tetrasaccharides containing 3-O-sulfated glucuronic
      acid from king crab cartilage chondroitin sulfate K and demonstrated that the
      disaccharide units containing 3-O-sulfated glucuronic acid were decomposed by
      chondroitinase ABC digestion (Sugahara, K., Tanaka, Y., Yamada, S., Seno, N.,
      Kitagawa, H., Haslam, S. M., Morris, H. R., and Dell, A. (1996) J. Biol. Chem.
      271, 26745-26754). The findings indicated the necessity to re-evaluate the
      disaccharide compositions of chondroitin sulfate preparations purified from other
      biological sources and analyzed using the above enzyme. In this study, to
      evaluate squid cartilage chondroitin sulfate E a series of even-numbered
      oligosaccharides were isolated after exhaustive digestion with sheep testicular
      hyaluronidase and subsequent fractionation by gel chromatography. The
      tetrasaccharide fraction was subfractionated by high performance liquid
      chromatography on an amine-bound silica column. Systematic structural analysis of
      five major fractions, h, l, m, n, and q, by fast atom bombardment mass
      spectrometry, enzymatic digestions in conjunction with capillary electrophoresis,
      and 500-MHz 1H NMR spectroscopy revealed one disulfated, three trisulfated, and
      one tetrasulfated tetrasaccharide structure: fraction h, GlcAbeta1
      3GalNAc(4S)beta1-4GlcAbeta1-3GalNAc(4S); fraction l, GlcA(3S)beta1
      3GalNAc(6S)beta1-4GlcAbeta1-3GalNAc(4S); fraction m, GlcA(3S)beta1
      3GalNAc(4S)beta1-4GlcAbeta1-3GalNAc(4S); fraction n, GlcAbeta1
      3GalNAc(4S,6S)beta1-4GlcAbeta1-3GalNAc(4S); and fraction q, GlcA(3S)beta1
      3GalNAc(4S,6S)beta1-4GlcAbeta1-3GalNAc(4S), where 3S, 4S, and 6S represent 3-O-,
      4-O- and 6-O-sulfate, respectively. The structures found in fractions h and m as
      well as the unsaturated counterpart of that found in fraction n have been
      reported, whereas those in fractions l and q are novel in that they contained
      unusual disulfated and trisulfated disaccharide units where GlcA(3S) is directly
      linked to GalNAc(6S) and GalNAc(4S,6S), respectively. These novel tetrasaccharide
      sequences are distinct from those found in other chondroitin sulfate isoforms and
      may play key roles in the biological functions and activities of chondroitin
      sulfate E not only from squid cartilage but also from mammalian cells and
      tissues.

PMID- 9242621
TI  - Pituitary adenylyl cyclase-activating peptide stimulates extracellular signal
      regulated kinase 1 or 2 (ERK1/2) activity in a Ras-independent, mitogen-activated
      protein Kinase/ERK kinase 1 or 2-dependent manner in PC12 cells.
AB  - Sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is
      critical for initiating differentiation of the PC12 cell to a sympathetic-like
      neurone. The neuropeptide, pituitary adenylyl cyclase-activating peptide (PACAP),
      has been demonstrated to cause cells to adopt a neuronal phenotype, although the
      mechanism of this activity is unclear. PACAP through its type I receptor
      stimulates a biphasic activation of ERK1/2; a >10-fold increase within 5 min,
      followed by a >5-fold increase that is sustained for >/=60 min. An equivalent
      stimulation is seen in PC12 cells expressing a dominant negative Ras mutant.
      However, the mitogen-activated kinase/ERK kinase 1/2 (MEK1/2) inhibitor PD98059
      blocked both PACAP-induced stimulation of ERK1/2 activity and neurite outgrowth.
      Thus, the activation signal from the PACAP type I receptor on the ERK1/2 cascade
      pathway is received downstream of Ras, either at Raf or MEK. Down-regulation of
      protein kinase C or its inhibition by calphostin C blocked the ability of PACAP
      to stimulate ERK1/2. We conclude that activation of PACAP type I receptor
      activates protein kinase C, which then activates the ERK1/2 cascade in a Ras
      independent manner at either Raf or MEK1/2.

PMID- 9242622
TI  - In vitro characterization of the novel proprotein convertase PC7.
AB  - Biochemical and enzymatic characterization of the novel proprotein convertase rat
      PC7 (rPC7) was carried out using vaccinia virus recombinants overexpressed in
      mammalian BSC40 cells. Pro-PC7 is synthesized as a glycosylated zymogen (101 kDa)
      and processed into mature rPC7 (89 kDa) in the endoplasmic reticulum. No
      endogenously produced soluble forms of this membrane-anchored protein were
      detected. A deletion mutant (65 kDa), truncated well beyond the expected C
      terminal boundary of the P-domain, produced soluble rPC7 in the culture medium.
      Enzymatic activity assays of rPC7 using fluorogenic peptidyl substrates indicated
      that the pH optimum, Ca2+ dependence, and cleavage specificity of this enzyme are
      largely similar to those of furin. However, with some substrates, cleavage
      specificity more closely resembled that of yeast kexin, suggesting differential
      processing of proprotein substrates by this novel convertase. We examined the
      rPC7- and human furin-mediated cleavage of synthetic peptides containing the
      processing sites of three proteins known to colocalize in situ with rPC7. Whereas
      both enzymes correctly processed the pro-parathyroid hormone tridecapeptide and
      the pro-PC4 heptadecapeptide, neither enzyme cleaved a pro-epidermal growth
      factor hexadecapeptide. Thus, this study establishes that rPC7 is an
      enzymatically functional subtilisin/kexin-like serine proteinase with a cleavage
      specificity resembling that of hfurin. In addition, we have demonstrated that
      rPC7 can correctly process peptide precursors that contain the processing sites
      of at least two potential physiological substrates.

PMID- 9242623
TI  - Reconstitution of functional eukaryotic ribosomes from Dictyostelium discoideum
      ribosomal proteins and RNA.
AB  - 40 and 60 S ribosomal subunits have been reconstituted in vitro from purified
      ribosomal RNA and ribosomal proteins of Dictyostelium discoideum. The
      functionality of the reconstituted ribosomes was demonstrated in in vitro mRNA
      directed protein synthesis. The reassembly proceeded well with immature
      precursors of ribosomal RNA but poorly if at all with mature cytoplasmic RNA
      species. Reassembly also required a preparation of small nuclear RNA(s), acting
      as morphopoietic factor(s).

PMID- 9242624
TI  - Shortened hydroxyacyl chains on lipid A of Escherichia coli cells expressing a
      foreign UDP-N-acetylglucosamine O-acyltransferase.
AB  - The first reaction of lipid A biosynthesis in Gram-negative bacteria is catalyzed
      by UDP-N-acetylglucosamine (UDP-GlcNAc) O-acyltransferase, the product of the
      lpxA gene. The reaction involves the transfer of an acyl chain from hydroxyacyl
      acyl carrier protein (ACP) to the glucosamine 3-OH position of UDP-GlcNAc. The
      lipid A isolated from Escherichia coli contains (R)-3-hydroxymyristate at the 3
      and 3' positions. Accordingly, LpxA of E. coli is highly selective for (R)-3
      hydroxymyristoyl-ACP over ACP thioesters of longer or shorter acyl chains. We now
      demonstrate that the lpxA gene from Neisseria meningitidis encodes a similar
      acyltransferase that selectively utilizes 3-hydroxylauroyl-ACP. Strains of E.
      coli harboring the temperature-sensitive lpxA2 mutation make very little lipid A
      and lose viability rapidly at 42 degrees C. We have created an E. coli strain in
      which the chromosomal lpxA2 mutation is complemented by the N. meningitidis lpxA
      gene introduced on a plasmid. This strain, RO138/pTO6, grows similarly to wild
      type cells at 42 degrees C and produces wild type levels of lipid A. However, the
      lipid A isolated from RO138/pTO6 contains mostly hydroxylaurate and
      hydroxydecanoate in the 3 and 3' positions. The strain RO138/pTO6 is more
      susceptible than wild type to certain antibiotics at 42 degrees C. This is the
      first report of an E. coli strain growing with shortened hydroxyacyl chains on
      its lipid A. The lpxA gene product appears to be a critical determinant of the
      length of the ester-linked hydroxyacyl chains found on lipid A in living cells.

PMID- 9242625
TI  - Identification of membrane insertion sequences of the rabbit gastric
      cholecystokinin-A receptor by in vitro translation.
AB  - To determine which amino acid sequences account for transmembrane folding of G7
      receptors, the membrane domain of the rabbit cholecystokinin-A (CCK-A) G-protein
      coupled receptor has been investigated by in vitro transcription/translation of
      two types of fusion vectors containing sequences that include putative
      transmembrane segments. First, the seven putative transmembrane domains of the
      CCK-A receptor were inserted individually into pGEM vectors beginning with the
      cDNA encoding the first 101 (HK-M0) or 139 (HK-M1) amino acids of the alpha
      subunit of the gastric H, K-ATPase. These were separated by the cDNA for the
      inserted transmembrane domains from the cDNA encoding the last 177 amino acids of
      the beta subunit of the H,K-ATPase containing five N-linked glycosylation
      consensus sequences (Bamberg, K., and Sachs, G. (1994) J. Biol. Chem. 269, 16909
      16919). Transcription/translation of these fusion vectors in rabbit reticulocyte
      lysate +/- dog pancreatic microsomes followed by SDS-polyacrylamide gel
      electrophoresis defined the presence of signal anchor sequences in HK-M0 by
      glycosylation and stop transfer sequences in HK-M1 by inhibition of
      glycosylation. Six out of the seven putative transmembrane domains had membrane
      insertion signals, but no membrane insertion activity was found for the H3
      segment in these vectors. To test the effect of specific upstream and downstream
      sequences on membrane insertion, vectors were also made starting with the cDNA
      encoding the N terminus of the CCK-A receptor separated from the last 177 amino
      acids of the H,K-ATPase beta subunit by cDNA encoding CCK-A receptor sequences of
      different lengths. In addition to transcription/translation, endoglycosidase H
      treatment was used to verify glycosylation when multiple bands were found in the
      presence of microsomes. The four positive charges in the loop between H1 and H2
      were required for the correct orientation of the first transmembrane domain. The
      H3 segment acted as a stop transfer sequence only when the whole N terminus and
      H3 were followed by the positive charges in the cytoplasmic loop between H3 and
      H4. The activity of H6 as a signal anchor sequence depended on preceding positive
      charges. These translation data using two types of fusion vectors establish a
      seven-transmembrane folding model using only in vitro translation for the CCK-A
      receptor beginning with two signal anchor sequences and then alternating stop
      transfer and signal anchor insertions. Positive charges between H1 and H2, H3 and
      H4, and H5 and H6 function as cytoplasmic anchors in the membrane folding of this
      receptor.

PMID- 9242626
TI  - Activated mast cells release extracellular type platelet-activating factor
      acetylhydrolase that contributes to autocrine inactivation of platelet-activating
      factor.
AB  - IgE-dependent and -independent activation of mouse bone marrow-derived mast cells
      (BMMC) elicited rapid and transient production of platelet-activating factor
      (PAF), which reached a maximal level by 2-5 min and was then degraded rapidly,
      returning to base-line levels by 10-20 min. Inactivation of PAF was preceded by
      the release of PAF acetylhydrolase (PAF-AH) activity, which reached a plateau by
      3-5 min and paralleled the release of beta-hexosaminidase, a marker of mast cell
      exocytosis. Immunochemical and molecular biological studies revealed that the PAF
      AH released from activated mast cells was identical to the plasma-type isoform.
      In support of the autocrine action of exocytosed PAF-AH, adding exogenous
      recombinant plasma-type PAF-AH markedly reduced PAF accumulation in activated
      BMMC. Furthermore, culture of BMMC with a combination of c-kit ligand,
      interleukin-1beta and interleukin-10 for > 24 h led to an increase in plasma-type
      PAF-AH expression, accompanied by a reduction in stimulus-initiated PAF
      production. Collectively, these results suggest that plasma-type PAF-AH released
      from activated mast cells sequesters proinflammatory PAF produced by these cells,
      thereby revealing an intriguing anti-inflammatory aspect of mast cells.

PMID- 9242627
TI  - Identification of a microtubule-binding domain in a cytoplasmic dynein heavy
      chain.
AB  - As a molecular motor, dynein must coordinate ATP hydrolysis with conformational
      changes that lead to processive interactions with a microtubule and generate
      force. To understand how these processes occur, we have begun to map functional
      domains of a dynein heavy chain from Dictyostelium. The carboxyl-terminal 10
      kilobase region of the heavy chain encodes a 380-kDa polypeptide that
      approximates the globular head domain. Attempts to further truncate this region
      fail to produce polypeptides that either bind microtubules or UV-vanadate cleave,
      indicating that the entire 10-kilobase fragment is necessary to produce a
      properly folded functional dynein head. We have further identified a region just
      downstream from the fourth P-loop that appears to constitute at least part of the
      microtubule-binding domain (amino acids 3182-3818). When deleted, the resulting
      head domain polypeptide no longer binds microtubules; when the excised region is
      expressed in vitro, it cosediments with added tubulin polymer. This microtubule
      binding domain falls within an area of the molecule predicted to form extended
      alpha-helices. At least four discrete sites appear to coordinate activities
      required to bind the tubulin polymer, indicating that the interaction of dynein
      with microtubules is complex.

PMID- 9242628
TI  - The related adhesion focal tyrosine kinase differentially phosphorylates p130Cas
      and the Cas-like protein, p105HEF1.
AB  - The related adhesion focal tyrosine kinase (RAFTK) is tyrosine-phosphorylated
      following beta1 integrin or B cell antigen receptor stimulation in human B cells.
      Two substrates that are tyrosine-phosphorylated following integrin ligation in B
      cells are p130(Cas) and the Cas family member human enhancer of filamentation 1
      (HEF1), both of which can associate with RAFTK. In this report we observed that
      RAFTK was involved in the phosphorylation of these two proteins. While a
      catalytically active RAFTK was required for both p130(Cas) and HEF1,
      phosphorylation of p130(Cas), but not of HEF1, was dependent on an intact
      autophosphorylation site (Tyr402) on RAFTK. To determine if RAFTK phosphorylated
      p130(Cas) and HEF1 directly or through an intermediate, we assayed the ability of
      RAFTK and of a Tyr402 mutant to phosphorylate purified HEF1 and p130(Cas)
      domains. RAFTK was able to phosphorylate the substrate domains of both p130(Cas)
      and HEF1, but only the C-terminal domain of p130(Cas). Furthermore, Tyr402, which
      mediates the binding of RAFTK to c-Src kinase, was required for the
      phosphorylation of the C-terminal domain of p130(Cas). These data suggest that
      RAFTK itself is sufficient for HEF1 phosphorylation, whereas a cooperation
      between RAFTK and Src kinases is required for the complete phosphorylation of
      p130(Cas).

PMID- 9242629
TI  - Conformational change of cytochrome P450 1A2 induced by phospholipids and
      detergents.
AB  - Recently, it was reported that the activity of rabbit P450 1A2 is markedly
      increased at elevated salt concentration (Yun, C-H., Song, M., Ahn, T., and Kim,
      H. (1996) J. Biol. Chem. 271, 31312-31316). The activity increase of P450 1A2
      coincides with the raised alpha-helix content and decreased beta-sheet content.
      The presence of phospholipid magnified this effect. Here, possible structural
      change of rabbit P450 1A2 accompanying the phospholipid-induced increase in its
      enzyme activity was investigated by circular dichroism, fluorescence
      spectroscopy, and absorption spectroscopy. Studies with the reconstituted system
      supported by cumene hydroperoxide or NADPH showed that the P450 1A2 activities
      were found to be dependent on the head group and hydrocarbon chain length of
      phospholipid. Phosphatidylcholines having short hydrocarbon chains with a carbon
      number of 8-12 were very efficient for reconstitution of the P450-catalyzed
      reactions supported by both cumene hydroperoxide and NADPH. It was found that the
      phospholipid increased the alpha-helix content and lowered the beta-sheet content
      of P450. Intrinsic fluorescence intensity is also increased in the presence of
      phospholipid. The low spin iron configuration of P450 1A2 shifted toward the high
      spin configuration by most of the phospholipids in the endoplasmic reticulum.
      Some synthetic phospholipids having short hydrocarbon chains with a carbon number
      of 10-12 caused a shift in the spin equilibrium of P450 1A2 toward low spin. The
      effect of detergents on the activity and conformation of P450 1A2 was also
      studied. It was found that the addition of detergents to P450 1A2 solution
      increased the enzyme activity of P450 1A2. Detergents also increased the alpha
      helix content and lowered the beta-sheet content of P450 1A2. Intrinsic
      fluorescence emissions also increased with the presence of detergents. Octyl
      glucoside and deoxycholate caused a shift toward high spin. On the other hand,
      cholate caused a shift toward low spin. It was found that the activity increase
      of rabbit P450 1A2 coincides with the conformational change including raised
      alpha-helix content. It is proposed that the interaction with the phospholipid
      molecules surrounding P450 1A2 in the endoplasmic reticulum is important for a
      functional conformation of P450 1A2 in a monooxygenase system including NADPH
      P450 reductase.

PMID- 9242630
TI  - Tryptophan fluorescence reports nucleotide-induced conformational changes in a
      domain of the ArsA ATPase.
AB  - The ars operon of plasmid R773 encodes an ATP-dependent extrusion pump for
      arsenite and antimonite in Escherichia coli. The ArsA ATPase is the catalytic
      subunit of the pump protein, with two nucleotide binding consensus sequences, one
      in the NH2-terminal half and one in the COOH-terminal half of the protein. A 12
      residue consensus sequence (DTAPTGHTIRLL) has been identified in ArsA homologs
      from eubacteria, archebacteria, fungi, plants, and animals. ArsA enzymes were
      constructed containing single tryptophan residues at either end of this conserved
      sequence. The emission spectrum of the fluorescence of the tryptophan on the COOH
      terminal end (Trp-159) indicated a relatively hydrophilic environment for this
      residue. An increase in intrinsic tryptophan fluorescence and a blue shift of the
      maximum emission wavelength were observed upon addition of MgATP, indicating
      movement of Trp-159 into a relatively less polar environment. No fluorescence
      response was observed with MgADP, with nonhydrolyzable ATP analogs, or with MgATP
      by catalytically inactive enyzmes. This suggests that the location Trp-159 is
      shifted only during hydrolysis of ATP. In contrast, the emission spectrum of Trp
      141, located on the NH2-terminal side of the consensus sequence, indicated a
      relatively nonpolar environment. The maximum emission wavelength red shifted upon
      addition of MgADP. MgATP slowly produced a response that correlated with product
      formation, suggesting that the environment of Trp-141 is sensitive only to MgADP
      binding. Thus, during ATP hydrolysis the COOH-terminal end of the conserved
      domain moves into a less polar environment, whereas the NH2-terminal end moves
      into a more hydrophilic environment as product is formed. A hypothesis is
      presented in which the conserved domain of ArsA and homologs is an energy
      transduction domain involved in transmission of the energy of ATP hydrolysis to
      biological functions such as transport.

PMID- 9242631
TI  - Sp1 is required for the early response of alpha2(I) collagen to transforming
      growth factor-beta1.
AB  - It is currently debated whether AP1 or Sp1 is the factor that mediates
      transforming growth factor beta1 (TGF-beta) stimulation of the human alpha2(I)
      collagen (COL1A2) gene by binding to an upstream promoter element (TbRE). The
      present study was designed to resolve this controversy by correlating expression
      of COL1A2, AP1, and Sp1 in the same cell line and under different experimental
      conditions. The results strongly indicate that Sp1 is required for the immediate
      early response of COL1A2 to TGF-beta and AP1 is not. The Sp1 inhibitor
      mithramycin blocked stimulation of alpha2(I) collagen mRNA accumulation by TGF
      beta, whereas the AP1 inhibitor curcumin had no effect. Furthermore, antibodies
      against Jun-B and c-Jun failed to identify immunologically related proteins in
      the TbRE-bound complex, irrespective of whether they were purified from untreated
      or TGF-beta-treated cells. AP1 did bind to the TbRE probe in vitro, but only in
      the absence of the upstream Sp1 recognition sequence. Based on this finding and
      DNA transfection results, we conclude that the AP1 sequence of the TbRE
      represents a cryptic site used under experimental conditions that either
      eliminate the more favorable Sp1 binding site or force the balance toward the
      less probable. Finally, a combination of cell transfections and DNA-binding
      assays excluded that COL1A2 transactivation involves the retinoblastoma gene
      product (pRb), an activator of Sp1, the pRb-related protein p107, an inhibitor of
      Sp1, or the Sp1-related repressor, Sp3.

PMID- 9242632
TI  - Dihydrolipoamide dehydrogenase-binding protein of the human pyruvate
      dehydrogenase complex. DNA-derived amino acid sequence, expression, and
      reconstitution of the pyruvate dehydrogenase complex.
AB  - Protein X, recently renamed dihydrolipoamide dehydrogenase-binding protein
      (E3BP), is required for anchoring dihydrolipoamide dehydrogenase (E3) to the
      dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes
      of eukaryotes. DNA and deduced protein sequences for E3BP of the human pyruvate
      dehydrogenase complex are reported here. With the exception of only a single
      lipoyl domain, the protein has a segmented multi-domain structure analogous to
      that of the E2 component of the complex. The protein has 46% amino acid sequence
      identity in its amino-terminal region with the second lipoyl domain of E2, 38%
      identity in its central region with the putative peripheral subunit-binding
      domain of E2, and 50% identity in its carboxyl-terminal region with the catalytic
      inner core domain of E2. The similarity in the latter domain stands in contrast
      to E3BP of Saccharomyces cerevisiae, which is quite different from its homologous
      transacetylase in this region. The putative catalytic site histidine residue
      present in the inner core domains of all dihydrolipoamide acyltransferases is
      replaced by a serine residue in human E3BP; thus, catalysis of coenzyme A
      acetylation by this protein is unlikely. Coexpression of cDNAs for E3BP and E2
      resulted in the formation of an E2.E3BP subcomplex that spontaneously
      reconstituted the pyruvate dehydrogenase complex in the presence of native E3 and
      recombinant pyruvate decarboxylase (E1).

PMID- 9242633
TI  - Ciliary neurotrophic factor stimulates the phosphorylation of two forms of STAT3
      in chick ciliary ganglion neurons.
AB  - Ciliary neurotrophic factor (CNTF) is a neuropoietic cytokine that was
      identified, purified, and cloned based on its neurotrophic activity on cultured
      chick ciliary ganglion neurons. The molecular mechanisms by which CNTF elicits
      its effects on these neurons are unknown. We have previously identified
      functional receptors for CNTF on ciliary ganglion neurons and demonstrated the
      CNTF-specific tyrosine phosphorylation of an approximately 90-kDa protein. Here
      we show that CNTF induced the rapid tyrosine phosphorylation and nuclear
      accumulation of this protein and identify it as an avian form of the
      transcription factor, STAT3. Identification was confirmed by its recognition with
      two distinct anti-STAT3 antibodies and the lack of binding to antibodies against
      STAT1, -2, -4, -5, or -6. The phosphorylation was stable for up to 2 h but
      required the continued presence of CNTF. CNTF also induced the tyrosine
      phosphorylation of a similar protein in cultured chick dorsal root ganglion and
      retinal neurons. In addition, we identify a second, 100-kDa form of STAT3 that
      appears in response to CNTF. Unlike previous reports, utilizing mammalian cell
      lines that detected a slower migrating form of STAT3 resulting from H7-sensitive
      protein phosphorylation, H7 did not prevent the appearance of the 100-kDa form in
      ciliary neurons. Thus, the 100-kDa avian protein may represent a novel form of
      CNTF-inducible STAT3.

PMID- 9242634
TI  - Splicing of intron-containing tRNATrp by the archaeon Haloferax volcanii occurs
      independent of mature tRNA structure.
AB  - We have investigated the requirements for mature tRNA structure in the in vivo
      splicing of the Haloferax volcanii, intron-containing tRNATrp RNA. A partial
      tRNATrp gene, which contained only the anticodon stem-loop region of the mature
      tRNA, was fused to a carrier yeast tRNA gene for expression in H. volcanii.
      Transcripts from this hybrid gene were found to be processed by endonuclease and
      ligase at the tRNATrp exon-intron boundaries. These results verify that the
      substrate recognition properties of the halobacterial endonuclease observed in
      vitro reflect the properties of this enzyme in vivo, namely that mature tRNA
      structure is not essential for recognition by the endonuclease. The independence
      of these reactions on mature tRNA provides further support for a relationship
      between archaeal tRNA and rRNA intron-processing systems and highlight a
      difference in the substrate recognition properties between the archaeal and
      eucaryal processing systems. The significance of these differences is discussed
      in light of the observation that the tRNA endonucleases of these organisms are
      related.

PMID- 9242635
TI  - Conformational changes of DNA induced by binding of Chironomus high mobility
      group protein 1a (cHMG1a). Regions flanking an HMG1 box domain do not influence
      the bend angle of the DNA.
AB  - High mobility group (HMG) proteins are thought to facilitate assembly of higher
      order chromatin structure through modulation of DNA conformation. In this work we
      investigate the bending of a 30-base pair DNA fragment induced by Chironomus HMG1
      (cHMG1a), and HMGI (cHMGI) proteins. The DNA bending was measured in solution by
      monitoring the end-to-end distance between fluorescence probes attached to
      opposite ends of the DNA fragment. The distance was measured by fluorescence
      energy transfer using a novel europium chelate as a fluorescence donor. These
      measurements revealed that the end-to-end distance in the 30-base pair DNA was
      decreased from approximately 100 A in free DNA to approximately 50.5 A in cHMG1a.
      DNA complex. The most probable DNA bending angle consistent with these distance
      measurements is about 150 degrees. The deletion of the charged regulatory domains
      located close to the C terminus of the HMG1 box domain of cHMG1a protein had no
      effect on the induced bend angle. The ability to induce a large DNA bend
      distinguishes the cHMG1 from the cHMGI protein. Only small perturbation of the
      DNA conformation was observed upon binding of the cHMGI protein. A strong DNA
      bending activity of cHMG1a and its relative abundance in the cell suggests that
      this protein plays a very important role in modulation of chromatin structure.

PMID- 9242636
TI  - CC chemokine receptor 5-mediated signaling and HIV-1 Co-receptor activity share
      common structural determinants. Critical residues in the third extracellular loop
      support HIV-1 fusion.
AB  - There is a close correspondence between the ability of RANTES and macrophage
      inflammatory proteins 1alpha and 1beta to activate CC chemokine receptor 5 (CCR5)
      and the ability to inhibit CCR5-dependent membrane fusion mediated by the
      envelope glycoprotein of human immunodeficiency virus (HIV), type 1. This finding
      suggests that some of the structural determinants for CC chemokine/CCR5
      interactions and CCR5 HIV-1 fusion co-receptor activity may be shared. Recent
      studies using human CCR5/CCR2B chimeras have suggested that the determinants of
      CCR5 co-receptor activity are complex and may involve multiple extracellular
      receptor domains and that viral co-receptor activity is dissociable from ligand
      dependent signaling responses. However, conclusive evidence demonstrating an
      important role for the second and third extracellular regions of human CCR5 is
      lacking. Furthermore, to determine whether the determinants for CCR5 co-receptor
      activity overlap with those required for agonist activity, studies that compare
      the chemokine specificity for inhibition of envelope-mediated cell fusion and the
      agonist profile of chimeric receptors are necessary. In the present report, using
      a series of CCR5/CCR2B chimeras we ascribe an important role for the second and
      third extracellular loop of CCR5 in supporting the co-receptor activity of CCR5.
      We also provide evidence that the intracytoplasmic tail of CCR5 does not play an
      important role in supporting HIV-1 entry. The hypothesis that the structural
      determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor
      activity may be shared was confirmed by two novel observations: first, the fusion
      activity supported by two hybrid receptors could be inhibited by both RANTES and
      monocyte chemoattractant protein-1, chemokines specific to CCR5 and CCR2B,
      respectively; and second, the chemokine specificity for inhibition of envelope
      mediated cell fusion matched the agonist profile of these hybrid receptors. These
      data shed new light on the structural determinants involved in these distinct
      activities of CCR5 and may have important implications for the development of
      CCR5-targeted anti-viral compounds.

PMID- 9242637
TI  - Localization of the major NF-kappaB-activating site and the sole TRAF3 binding
      site of LMP-1 defines two distinct signaling motifs.
AB  - The TRAF3 molecule interacts with the cytoplasmic carboxyl terminus (COOH
      terminus) of the Epstein-Barr virus-encoded oncogene LMP-1. NF-kappaB activation
      is a downstream signaling event of tumor necrosis factor receptor-associated
      factor (TRAF) molecules in other signaling systems (CD40 for example) and is an
      event caused by LMP-1 expression. One region capable of TRAF3 interaction in LMP
      1 is the membrane-proximal 45 amino acids (188-242) of the COOH terminus. We show
      that this region contains the only site for binding of TRAF3 in the 200-amino
      acid COOH terminus of LMP-1. The site also binds TRAF2 and TRAF5, but not TRAF6.
      TRAF3 binds to critical residues localized between amino acids 196 and 212
      (HHDDSLPHPQQATDDSG), including the PXQX(T/S) motif, that share limited identity
      to the CD40 receptor TRAF binding site (TAAPVQETL). Mutation of critical residues
      in the TRAF3 binding site of LMP-1 that prevents binding of TRAF2, TRAF3, and
      TRAF5 does not affect NF-kappaB-activating potential. Deletion mapping localized
      the major NF-kappaB activating region of LMP-1 to critical residues in the distal
      4 amino acids of the COOH terminus (383-386). Therefore, TRAF3 binding and NF
      kappaB activation occur through two separate motifs at opposite ends of the LMP-1
      COOH-terminal sequence.

PMID- 9242638
TI  - Differential interactions of Id proteins with basic-helix-loop-helix
      transcription factors.
AB  - Dimerization of three Id proteins (Id1, Id2, and Id3) with the four class A E
      proteins (E12, E47, E2-2, and HEB) and two groups of class B proteins, the
      myogenic regulatory factors (MRFs: MyoD, myogenin, Myf-5 and MRF4/Myf-6), and the
      hematopoietic factors (Scl/Tal-1, Tal-2, and Lyl-1) were tested in a quantitative
      yeast 2-hybrid assay. All three Ids bound with high affinity to E proteins, but a
      much broader range of interactions was observed between Ids and the class B
      factors. Id1 and Id2 interacted strongly with MyoD and Myf-5 and weakly with
      myogenin and MRF4/Myf-6, whereas Id3 interacted weakly with all four MRFs.
      Similar specificities were observed in co-immunoprecipitation and mammalian 2
      hybrid analyses. No interactions were found between the Ids and any of the
      hematopoietic factors. Each Id was able to disrupt the ability of E protein-MyoD
      complexes to transactivate from a muscle creatine kinase reporter construct in
      vivo. Finally, mutagenesis experiments showed that the differences between Id1
      and Id3 binding map to three amino acids in the first helix and to a small
      cluster of upstream residues. The Id proteins thus display a signature range of
      interactions with all of their potential dimerization partners and may play a
      role in myogenesis which is distinct from that in hematopoiesis.

PMID- 9242639
TI  - Changing ligand specificities of alphavbeta1 and alphavbeta3 integrins by
      swapping a short diverse sequence of the beta subunit.
AB  - Integrins mediate signal transduction through interaction with multiple cellular
      or extracellular matrix ligands. Integrin alphavbeta3 recognizes fibrinogen, von
      Willebrand factor, and vitronectin, while alphavbeta1 does not. We studied the
      mechanisms for defining ligand specificity of these integrins by swapping the
      highly diverse sequences in the I domain-like structure of the beta1 and beta3
      subunits. When the sequence CTSEQNC (residues 187-193) of beta1 is replaced with
      the corresponding CYDMKTTC sequence of beta3, the ligand specificity of
      alphavbeta1 is altered. The mutant (alphavbeta1-3-1), like alphavbeta3,
      recognizes fibrinogen, von Willebrand factor, and vitronectin (a gain-of-function
      effect). The alphavbeta1-3-1 mutant is recruited to focal contacts on fibrinogen
      and vitronectin, suggesting that the mutant transduces intracellular signals on
      adhesion. The reciprocal beta3-1-3 mutation blocks binding of alphavbeta3 to
      these multiple ligands and to LM609, a function-blocking anti-alphavbeta3
      antibody. These results suggest that the highly divergent sequence is a key
      determinant of integrin ligand specificity. Also, the data support a recent
      hypothetical model of the I domain of beta, in which the sequence is located in
      the ligand binding site.

PMID- 9242640
TI  - Rtg3p, a basic helix-loop-helix/leucine zipper protein that functions in
      mitochondrial-induced changes in gene expression, contains independent activation
      domains.
AB  - Rtg3p and Rtg1p are basic helix-loop-helix/leucine zipper protein transcription
      factors in yeast that interact and bind to sites in an upstream activation
      sequence element in the 5'-flanking region of CIT2, a gene encoding a peroxisomal
      isoform of citrate synthase. These factors are required both for basal expression
      of CIT2 and its elevated expression in cells with dysfunctional mitochondria,
      such as in respiratory-deficient petite cells lacking mitochondrial DNA (rho
      degrees ). This elevated expression of CIT2 is called the retrograde response.
      Here we show that fusion constructs between the Gal4p DNA binding domain and
      Rtg3p transactivate the expression of a LacZ reporter gene under the control of a
      GAL1 promoter element. We have identified two activation domains in Rtg3p: a
      strong carboxyl-terminal domain from amino acids 375-486, and a weaker amino
      terminal domain from amino acids 1-175; neither of these activation domains
      contain the bHLH/Zip motif. We have also identified a serine/threonine-rich
      domain of Rtg3p within amino acids 176-282 that is inhibitory to transactivation.
      In addition, the transcriptional activity of the Gal4-Rtg3p fusion proteins does
      not require either Rtg1p or Rtg2p; the latter is a protein containing an hsp70
      like ATP binding domain that is also necessary for CIT2 expression. In contrast,
      transcriptional activation by Gal4-Rtg1p fusion proteins requires the Rtg1p basic
      helix-loop-helix/leucine zipper protein domain, as well as Rtg3p and Rtg2p. These
      data suggest that transcriptional activation by the Rtg1p-Rtg3p complex is
      largely the function of Rtg3p. Experiments are also presented suggesting that
      Rtg3p is limiting for gene expression in respiratory-competent (rho+) cells.

PMID- 9242641
TI  - Expression of the ryanodine receptor type 3 calcium release channel during
      development and differentiation of mammalian skeletal muscle cells.
AB  - In vertebrate skeletal muscles, the type 1 isoform of ryanodine receptor (RyR1)
      is essential in triggering contraction by releasing Ca2+ from the sarcoplasmic
      reticulum in response to plasma membrane depolarisation. Recently, the presence
      of another RyR isoform, RyR3, has been detected in mammalian skeletal muscle
      cells, raising the question of the eventual relevance of RyR3 for muscle cell
      physiology. The expression of RyR3 was investigated during differentiation of
      skeletal muscle cells. Using antibodies able to distinguish the different RyR
      isoforms and Western blot analysis, the RyR3 protein was detected in the
      microsomal fractions of differentiated skeletal muscle cells but not of
      undifferentiated cells. Accordingly, blocking muscle differentiation by the
      addition of either transforming growth factor-beta or basic fibroblast growth
      factor prevented the expression of the RyR3 protein. In differentiated skeletal
      muscle cells, RyR3 was expressed independent of cell fusion and myotube
      formation. The expression of RyR3 was also investigated during development of the
      diaphragm muscle. The RyR3 content in the diaphragm muscle increased between the
      late stage of fetal development and the first postnatal days. However, at
      variance with RyR1, which reached maximum levels of expression 2-3 weeks after
      birth, the expression of RyR3 was found to be higher in the neonatal phase of the
      diaphragm muscle development (2-15 days after birth) than in the same muscle from
      adult mice. The differential content of RyR3 in adult skeletal muscles was found
      not to be mediated by neurotrophic factors or electrical activity. These findings
      indicate that RyR3 is preferentially expressed in differentiated skeletal muscle
      cells. In addition, during skeletal muscle development, its expression is
      regulated differently from that of RyR1.

PMID- 9242642
TI  - Cross-talk between the platelet-derived growth factor and the insulin signaling
      pathways in 3T3-L1 adipocytes.
AB  - Phosphatidylinositol (PI) 3-kinase is activated by various growth factors such as
      PDGF (platelet-derived growth factor) and insulin. The aim of the present study
      was to determine whether PDGF could modulate insulin activation of PI 3-kinase in
      3T3-L1 adipocytes. When cells were preincubated for 5-15 min with PDGF, PI 3
      kinase activity associated to insulin receptor substrate 1 (IRS 1) in response to
      insulin was decreased, due to reduced association of the PI 3-kinase p85 subunit
      with IRS 1. In addition, following this PDGF pretreatment, the tyrosine
      phosphorylation of IRS 1 in response to insulin and its electrophoretic mobility
      were diminished. The change in the mobility of IRS 1 could be attributed to PDGF
      induced serine/threonine phosphorylation of the protein which was partly
      inhibited by PI 3-kinase inhibitors. By contrast, epidermal growth factor, which
      does not stimulate PI 3-kinase, had no effect on the association of PI 3-kinase
      with IRS 1 in response to insulin. This series of results indicates that the PDGF
      induced serine/threonine phosphorylation of IRS 1 could be due to activation of
      PI 3-kinase pathway. Furthermore, this phosphorylation of IRS 1 is associated
      with a decrease in its tyrosine phosphorylation by insulin and in its association
      with the p85 subunit of PI 3-kinase. This study suggests that a cross-talk exists
      between the different pathways stimulated by PDGF and insulin in intact cells.

PMID- 9242643
TI  - Overexpression, purification, and characterization of the SbcCD protein from
      Escherichia coli.
AB  - The sbcC and sbcD genes mediate palindrome inviability in Escherichia coli. The
      sbcCD operon has been cloned into the plasmid pTrc99A under the control of the
      strong trc promoter and introduced into a strain carrying a chromosomal deletion
      of sbcCD. The SbcC and SbcD polypeptides were overexpressed to 6% of total cell
      protein, and both polypeptides copurified in a four-step purification procedure.
      Purified SbcCD is a processive double-strand exonuclease that has an absolute
      requirement for Mn2+ and uses ATP as a preferred energy source. Gel filtration
      chromatography and sedimentation equilibrium analyses were used to show that the
      SbcC and SbcD polypeptides dissociate at some stage after purification and that
      this dissociation is reversed by the addition of Mn2+. We demonstrate that SbcD
      has the potential to form a secondary structural motif found in a number of
      protein phosphatases and suggest that it is a metalloprotein that contains the
      catalytic center of the SbcCD exonuclease.

PMID- 9242644
TI  - Molecular analysis of a novel winged helix protein, WIN. Expression pattern, DNA
      binding property, and alternative splicing within the DNA binding domain.
AB  - We have cloned a novel winged helix factor, WIN, from the rat insulinoma cell
      line, INS-1. Northern blot analysis demonstrated that WIN is highly expressed in
      a variety of insulinoma cell lines and rat embryonic pancreas and liver. In
      adults, WIN expression was detected in thymus, testis, lung, and several
      intestinal regions. We determined the DNA sequences bound in vitro by baculovirus
      expressed WIN protein in a polymerase chain reaction-based selection procedure.
      WIN was found to bind with high affinity to the selected sequence 5'-AGATTGAGTA
      3', which is similar to the recently identified HNF-6 binding sequence 5'
      DHWATTGAYTWWD-3' (where W = A or T, Y = T or C, H is not G, and D is not C). We
      have isolated human WIN cDNAs by library screening and 5'-rapid amplification of
      cDNA ends. Sequence analysis indicates that the carboxyl terminus of human WIN
      has been previously isolated as a putative phosphorylation substrate, MPM2
      reactive phosphoprotein 2 (MPP2); WIN may be regulated by phosphorylation.
      Alignment of the rat and human WIN cDNAs and their comparison with mouse genomic
      sequence revealed that the WIN DNA binding domain is encoded by four exons, two
      of which (exons 4 and 6) are alternatively spliced to generate at least three
      classes of mRNA transcripts. These transcripts were shown by RNase protection
      assay to be differentially expressed in different tissues. Alternative splicing
      within the winged helix DNA binding domain might result in modulation of DNA
      binding specificity.

PMID- 9242645
TI  - Inactivation of thrombin by antithrombin is accompanied by inactivation of
      regulatory exosite I.
AB  - Exosite I of the blood clotting proteinase, thrombin, mediates interactions of
      the enzyme with certain inhibitors, physiological substrates and regulatory
      proteins. Specific binding of a fluorescein-labeled derivative of the COOH
      terminal dodecapeptide of hirudin ([5F] Hir54-65) to exosite I was used to probe
      changes in the function of the regulatory site accompanying inactivation of
      thrombin by its physiological serpin inhibitor, antithrombin. Fluorescence
      monitored equilibrium binding studies showed that [5F]Hir54-65 and Hir54-65 bound
      to human alpha-thrombin with dissociation constants of 26 +/- 2 nM and 38 +/- 5
      nM, respectively, while the affinity of the peptides for the stable thrombin
      antithrombin complex was undetectable (>/=200-fold weaker). Kinetic studies
      showed that the loss of binding sites for [5F]Hir54-65 occurred with the same
      time-course as the loss of thrombin catalytic activity. Binding of [5F] Hir54-65
      and Hir54-65 to thrombin was correlated quantitatively with partial inhibition of
      the rate of the thrombin-antithrombin reaction, maximally decreasing the
      bimolecular rate constants 1.7- and 2.1-fold, respectively. These results support
      a mechanism in which thrombin and the thrombin-Hir54-65 complex can associate
      with antithrombin and undergo formation of the covalent thrombin-antithrombin
      complex at modestly different rates, with inactivation of exosite I leading to
      dissociation of the peptide occurring subsequent to the rate-limiting
      inactivation of thrombin. This mechanism may function physiologically in
      localizing the activity of thrombin by allowing inactivation of thrombin that is
      bound in exosite I-mediated complexes with regulatory proteins, such as
      thrombomodulin and fibrin, without prior dissociation of these complexes.
      Concomitant with inactivation of thrombin, the thrombin-antithrombin complex may
      be irreversibly released due to exosite I inactivation.

PMID- 9242646
TI  - Molecular cloning, expression, and sequence analysis of the endoglycoceramidase
      II gene from Rhodococcus species strain M-777.
AB  - Endoglycoceramidase (EGCase (EC 3.2.1.123)) is a hydrolase that hydrolyzes the
      linkage between the oligosaccharide and ceramide of various glycosphingolipids.
      This paper describes the molecular cloning and expression of EGCase II, one of
      the isoforms of EGCases. The gene encoding EGCase II was obtained by screening of
      a genomic DNA library from Rhodococcus sp. strain M-777 constructed in pUC19 with
      oligonucleotide probes deduced from a partial amino acid sequence of the enzyme
      protein. Recombinant Escherichia coli cells in which the EGCase II gene was
      expressed produced 14 units of the enzyme per liter of culture medium but did not
      produce sphingomyelinase. Recombinant EGCase II was a functioning enzyme with
      substrate specificity identical to that of the wild-type enzyme. Sequence
      analysis showed the presence of an open reading frame of 1470 base pairs encoding
      490 amino acids. The N-terminal region of the deduced amino acid sequence had the
      general pattern of signal peptides of secreted prokaryotic proteins.
      Interestingly, the consensus sequence in the active site region of the endo-1,4
      beta-glucanase family A was found in the amino acid sequence of EGCase II.

PMID- 9242647
TI  - An internal cysteine is involved in the thioredoxin-dependent activation of
      sorghum leaf NADP-malate dehydrogenase.
AB  - The chloroplastic NADP-malate dehydrogenase is activated by thiol/disulfide
      interchange with reduced thioredoxins. Previous experiments showed that four
      cysteines located in specific N- and carboxyl-terminal extensions were implicated
      in this process, leading to a model where no internal cysteine was involved in
      activation. In the present study, the role of the conserved four internal
      cysteines was investigated. Surprisingly, the mutation of cysteine 207 into
      alanine yielded a protein with accelerated activation time course, whereas the
      mutations of the three other internal cysteines into alanines yielded proteins
      with unchanged activation kinetics. These results suggested that cysteine 207
      might be linked in a disulfide bridge with one of the four external cysteines,
      most probably with one of the two amino-terminal cysteines whose mutation
      similarly accelerates the activation rate. To investigate this possibility,
      mutant malate dehydrogenases (MDHs) where a single amino-terminal cysteine was
      mutated in combination with the mutation of both carboxyl-terminal cysteines were
      produced and purified. The C29S/C365A/C377A mutant MDH still needed activation by
      reduced thioredoxin, while the C24S/C365A/C377A mutant MDH exhibited a
      thioredoxin-insensitive spontaneous activity, leading to the hypothesis that a
      Cys24-Cys207 disulfide bridge might be formed during the activation process.
      Indeed, an NADP-MDH where the cysteines 29, 207, 365, and 377 are mutated yielded
      a permanently active enzyme very similar to the previously created permanently
      active C24S/C29S/C365A/C377A mutant. A two-step activation model involving a
      thioredoxin-mediated disulfide isomerization at the amino terminus is proposed.

PMID- 9242648
TI  - Estrogen receptors alpha and beta form heterodimers on DNA.
AB  - The estrogen receptor (ER) is expressed in two forms, ERalpha and ERbeta. Here we
      show that ERalpha and ERbeta, expressed both in vitro and in vivo, form
      heterodimers which bind to DNA with an affinity (Kd of approximately 2 nM)
      similar to that of ERalpha and greater than that of ERbeta homodimers. Mutation
      analysis of the hormone binding domain of ERalpha suggests that the dimerization
      interface required to form heterodimers with ERbeta is very similar but not
      identical to that required for homodimer formation. The heterodimer, like the
      homodimers, are capable of binding the steroid receptor coactivator-1 when bound
      to DNA and stimulating transcription of a reporter gene in transfected cells.
      Given the relative expression of ERalpha and ERbeta in tissues and the difference
      in DNA binding activity between ERalpha/ERbeta heterodimers and ERbeta it seems
      likely that the heterodimer is functionally active in a subset of target cells.

PMID- 9242649
TI  - The trp RNA-binding attenuation protein (TRAP) from Bacillus subtilis binds to
      unstacked trp leader RNA.
AB  - TRAP (trp RNA-binding attenuation protein) is a tryptophan-activated RNA-binding
      protein that regulates expression of the trp biosynthetic genes by binding to a
      series of GAG and UAG trinucleotide repeats generally separated by two or three
      spacer nucleotides. Previously, we showed that TRAP contains 11 identical
      subunits arranged in a symmetrical ring. Based on this structure, we proposed a
      model for the TRAP.RNA interaction where the RNA wraps around the protein with
      each repeat of the RNA contacting one or a combination of two adjacent subunits
      of the TRAP oligomer. Here, we have shown that RNAs selected in vitro based on
      their ability to bind tryptophan-activated TRAP contain multiple G/UAG repeats
      and show a strong bias for pyrimidines as the spacer nucleotides between these
      repeats. The affinity of the TRAP.RNA interaction displays a nonlinear
      temperature dependence, increasing between 5 degrees C and 47 degrees C and then
      decreasing from 47 degrees C to 67 degrees C. Differential scanning calorimetry
      and circular dichroism spectroscopy demonstrate that TRAP is highly thermostable
      with few detectable changes in the structure between 25 degrees C and 70 degrees
      C, suggesting that the temperature dependence of this interaction reflects
      changes in the RNA. Results from circular dichroism and UV absorbance
      spectroscopy support this hypothesis, demonstrating that trp leader RNA becomes
      unstacked upon binding TRAP. We propose that the bias toward pyrimidines in the
      spacer nucleotides of the in vitro selected RNAs represents the inability of Us
      and Cs to form stable base stacking interactions, which allows the flexibility
      needed for the RNA to wrap around the TRAP oligomer.

PMID- 9242650
TI  - Internal electron transfer in Cu-heme oxidases. Thermodynamic or kinetic control?
AB  - We present novel experimental evidence that, starting with the oxidized enzyme,
      the internal electron transfer in cytochrome c oxidase is kinetically controlled.
      The anaerobic reduction of the oxidized enzyme by ruthenium hexamine has been
      followed in the absence and presence of CO or NO, used as trapping ligands for
      reduced cytochrome a3. In the presence of NO, the rate of formation of the
      cytochrome a32+-NO adduct is independent of the concentration of ruthenium
      hexamine and of NO, indicating that in the oxidized enzyme cytochrome a and a3
      are not in very rapid redox equilibrium; on the other hand, CO proved to be a
      poor "trapping" ligand. We conclude that the intrinsic rate constant for a --> a3
      electron transfer in the oxidized enzyme is 25 s-1. These data are discussed with
      reference to a model (Verkhovsky, M. I., Morgan, J. E., and Wikstrom, M. (1995)
      Biochemistry 34, 7483-7491) in which H+ diffusion and/or binding at the binuclear
      site is the rate-limiting step in the reduction of cytochrome a3 in the oxidized
      enzyme.

PMID- 9242651
TI  - Active site modification of factor VIIa affects interactions of the protease
      domain with tissue factor.
AB  - In the initiation of coagulation, tissue factor (TF) allosterically activates the
      serine protease factor VIIa (VIIa) through specific interactions with protease
      domain residues. These interactions, and consequently affinity for TF, may be
      influenced by conformational changes in the protease domain that result from
      zymogen-enzyme transition or occupancy of the active site by tight binding
      inhibitors. In functional competition and direct binding analysis, we determined
      affinities for zymogen and enzyme species of wild-type VII and of mutants at
      protease domain residues that contact TF. We demonstrate that TF binding is not
      influenced by zymogen activation, indicating that the protease domain of zymogen
      and enzyme dock similarly with TF. In contrast, active site occupancy enhanced
      the affinity for TF by predominantly decreasing the dissociation rate of the
      TF.VIIa complex. Of the three interface residues studied, only Met306 played a
      major role in the inhibitor-induced increase in affinity. Met306 is also
      important for transmitting the allosteric changes from TF to the active site,
      resulting in enhanced catalysis. This study thus provides evidence for a
      bidirectional conformational interdependence of the interface residue Met306 and
      the active site of VIIa.

PMID- 9242652
TI  - Synthesis and characterization of selenolipoylated H-protein of the glycine
      cleavage system.
AB  - H-protein of the glycine cleavage system has a lipoic acid prosthetic group.
      Selenolipoic acid is a lipoic acid analog in which both sulfur atoms are replaced
      by selenium atoms. Two isoforms of bovine lipoyltransferase that are responsible
      for the attachment of lipoic acid to H-protein had an affinity for selenolipoyl
      AMP and transferred the selenolipoyl moiety to bovine apoH-protein comparable to
      lipoyl-AMP. Selenolipoylated H-protein was overexpressed in Escherichia coli and
      purified. Selenolipoylated H-protein was 26% as effective as lipoylated H-protein
      in the glycine decarboxylation reaction, in which reduction of the diselenide
      bond of selenolipoylated H-protein is catalyzed by P-protein. The diselenide form
      of selenolipoylated H-protein was a poor substrate for L-protein, and the rate of
      reduction was 0.5% of that of lipoylated H-protein. The rate of the overall
      glycine cleavage reaction with selenolipoylated H-protein was <1% of that with
      lipoylated H-protein. These results are consistent with the difference in the
      redox potential between the diselenide and disulfide bonds. In contrast,
      selenolipoylated H-protein showed three times as high glycine-14CO2 exchange
      activity as lipoylated H-protein, presumably because the rate of reoxidation of
      reduced selenolipoylated H-protein is much higher than that of lipoylated H
      protein.

PMID- 9242653
TI  - The 46-kDa mannose 6-phosphate receptor contains multiple binding sites for
      clathrin adaptors.
AB  - The two known mannose 6-phosphate receptors (MPR46 and MPR300) both mediate the
      transport of Man-6-P-containing lysosomal proteins to lysosomes. However, the
      MPRs cannot be detected in lysosomes, instead they recycle between the plasma
      membrane and endosomes and between endosomes and the trans-Golgi network. Both,
      endocytosis from the plasma membrane and budding of transport vesicles from the
      trans-Golgi network involves the interaction of the receptor with the clathrin
      coated vesicles-associated protein complexes AP1 and AP2. We have analyzed this
      interaction between the Golgi-restricted AP1 complex and the plasma membrane
      restricted AP2 complex with the MPR46 tail in vitro by using a biosensor. AP1 and
      AP2 both bind to and dissociate from the MPR46 tail with similar kinetics. Using
      synthetic peptides corresponding to different MPR receptor tail regions in
      inhibition and binding studies, a common high affinity binding site for AP1 and
      AP2 and two separate high affinity binding sites for AP1 and AP2, respectively,
      were identified.

PMID- 9242654
TI  - Prostaglandin E2 amplifies cytosolic phospholipase A2- and cyclooxygenase-2
      dependent delayed prostaglandin E2 generation in mouse osteoblastic cells.
      Enhancement by secretory phospholipase A2.
AB  - We used the MC3T3-E1 cell line, which originates from C57BL/6J mouse that is
      genetically type IIA secretory phospholipase A2 (sPLA2)-deficient, to reveal the
      type IIA sPLA2-independent route of the prostanglandin (PG) biosynthetic pathway.
      Kinetic and pharmacological studies showed that delayed PGE2 generation by this
      cell line in response to interleukin (IL)-1beta and tumor necrosis factor alpha
      (TNFalpha) was dependent upon cytosolic phospholipase A2 (cPLA2) and
      cyclooxygenase (COX)-2. Expression of these two enzymes was reduced by cPLA2 or
      COX-2 inhibitors and restored by adding exogenous arachidonic acid or PGE2,
      indicating that PGE2 produced by these cells acted as an autocrine amplifier of
      delayed PGE2 generation through enhanced cPLA2 and COX-2 expression. Exogenous
      addition or enforced expression of type IIA sPLA2 significantly increased IL
      1beta/TNFalpha-initiated PGE2 generation, which was accompanied by increased
      expression of both cPLA2 and COX-2 and suppressed by inhibitors of these enzymes.
      Thus, our results revealed a particular cross-talk between the two PLA2 enzymes
      and COX-2 for delayed PGE2 biosynthesis by a type IIA sPLA2-deficient cell line.
      cPLA2 is responsible for initiating COX-2-dependent delayed PGE2 generation, and
      sPLA2, if introduced, enhances PGE2 generation by increasing cPLA2 and COX-2
      expression via endogenous PGE2.

PMID- 9242655
TI  - Recognition of nonconserved bases in the P22 operator by P22 repressor requires
      specific interactions between repressor and conserved bases.
AB  - The ability of P22 repressor protein to distinguish between the six naturally
      occurring operator binding sites is critically important in determining whether
      the bacteriophage chooses to grow lytically or lysogenically. We have shown that
      changes in the highly conserved bases at P22 operator positions 3, 5, 6, and 7
      prevent specific binding of P22 repressor. Moreover, studies of mutant proteins
      identified the three repressor amino acids that directly contact these conserved
      bases. The pattern of operator sequence conservation permits these direct amino
      acid-base pair interactions to occur in all except one of the 12 operator half
      sites in the phage chromosome. Therefore, repressor differential affinity for
      these sites cannot be due to these highly conserved base pair-amino acid
      interactions. Our binding studies show that the nonconserved bases at positions 2
      and 4 also play an important role in determining the relative affinity of the
      naturally occurring P22 operators for P22 repressor. Our data indicate that the
      direct contacts between the three solvent-exposed amino acids and the conserved
      bases in the binding site lock these amino acids in place, forming a scaffold
      allowing the rest of the amino acids side chains to form weaker interactions with
      the nonconserved bases in the binding site.

PMID- 9242656
TI  - Trapping an activated conformation of mammalian carbamyl-phosphate synthetase.
AB  - The amidotransferase or glutaminase domain (GLN domain) of mammalian carbamyl
      phosphate synthetase II (CPSase II) catalyzes glutamine hydrolysis and transfers
      ammonia to the synthetase domain (CPS domain), where carbamyl phosphate formation
      is catalyzed in three consecutive reactions. The GLN and CPS domains are part of
      a single polypeptide and are connected via a 29-amino acid chain segment (GC
      linker). In contrast, the two comparable domains of Escherichia coli CPSase are
      not fused, but are separate, noncovalently associated subunits. To establish the
      function of the GC linker in mammalian CPSase, it was deleted, and the two
      domains were directly fused. The deletion mutant not only catalyzed glutamine
      dependent carbamyl phosphate synthesis, but was activated 10-fold relative to its
      wild-type counterpart. However, ammonia-dependent synthesis of carbamyl phosphate
      was abolished, indicating that ammonia no longer had access to the active site on
      the CPS domain. The mutant was still sensitive to inhibition by the allosteric
      effector UTP, but was no longer activated by the allosteric effector
      phosphoribosyl pyrophosphate, although evidence indicated that the latter could
      bind to the enzyme. The linker appears to serve as a spacer that allows the
      complex to cycle between two conformations, an open low activity form in which
      the ammonia site on the CPS domain is accessible and an activated conformation in
      which the ammonia generated in situ from glutamine is directly channeled to the
      CPS active site and access to exogenous ammonia is blocked.

PMID- 9242657
TI  - Activation by fusion of the glutaminase and synthetase subunits of Escherichia
      coli carbamyl-phosphate synthetase.
AB  - Escherichia coli carbamyl-phosphate synthetase consists of two subunits that act
      in concert to synthesize carbamyl phosphate. The 40-kDa subunit is an
      amidotransferase (GLN subunit) that hydrolyzes glutamine and transfers ammonia to
      the 120-kDa synthetase subunit (CPS subunit). The enzyme can also catalyze
      ammonia-dependent carbamyl phosphate synthesis if provided with exogenous
      ammonia. In mammalian cells, homologous amidotransferase and synthetase domains
      are carried on a single polypeptide chain called CAD. Deletion of the 29-residue
      linker that bridges the GLN and CPS domains of CAD stimulates glutamine-dependent
      carbamyl phosphate synthesis and abolishes the ammonia-dependent reaction (Guy,
      H. I., and Evans, D. R. (1997) J. Biol. Chem. 272, 19906-19912), suggesting that
      the deletion mutant is trapped in a closed high activity conformation. Since the
      catalytic mechanisms of the mammalian and bacterial proteins are the same, we
      anticipated that similar changes in the function of the E. coli protein could be
      produced by direct fusion of the GLN and CPS subunits. A construct was made in
      which the intergenic region between the contiguous carA and carB genes was
      deleted and the sequences encoding the carbamyl-phosphate synthetase subunits
      were fused in frame. The resulting fusion protein was activated 10-fold relative
      to the native protein, was unresponsive to the allosteric activator ornithine,
      and could no longer use ammonia as a nitrogen donor. Moreover, the functional
      linkage that coordinates the rate of glutamine hydrolysis with the activation of
      bicarbonate was abolished, suggesting that the protein was locked in an activated
      conformation similar to that induced by the simultaneous binding of all
      substrates.

PMID- 9242658
TI  - Ca2+ binding to the first epidermal growth factor-like domain of factor VIIa
      increases amidolytic activity and tissue factor affinity.
AB  - Coagulation factor VIIa belongs to a family of homologous enzymes, including
      factors IXa and Xa and activated protein C, composed of two epidermal growth
      factor-like domains located between an N-terminal domain rich in gamma
      carboxyglutamic acid residues and a C-terminal serine protease domain. The first
      epidermal growth factor-like domain in factor VIIa contains a Ca2+ binding site,
      the function of which is largely unknown. Site-directed mutagenesis of two Ca2+
      liganding Asp residues in this domain abolished Ca2+ binding and resulted in a 2
      3-fold decrease in amidolytic activity at optimal Ca2+ concentrations. The lower
      amidolytic activity persisted in complex with soluble tissue factor, apparently
      due to a lower kcat of the mutant factor VIIa. Mutant and wild-type factor VIIa
      bound to lipidated tissue factor were equally efficient activators of factor X.
      The dissociation constants, derived from amidolytic activity and surface plasmon
      resonance measurements, were 2-5 nM and 50-60 nM for the interactions between
      wild-type and mutant factor VIIa, respectively, and soluble tissue factor.
      Binding to lipidated tissue factor was characterized by dissociation constants of
      7.5 pM for factor VIIa and 160 pM for the factor VIIa mutant. Hence, a functional
      Ca2+ binding site in the first epidermal growth factor-like domain added 7-8
      kJ/mol to the total binding energy of the interaction with both lipidated and
      soluble tissue factor.

PMID- 9242659
TI  - A novel small conductance Ca2+-activated K+ channel blocker from Oxyuranus
      scutellatus taipan venom. Re-evaluation of taicatoxin as a selective Ca2+ channel
      probe.
AB  - Taicatoxin, isolated from the venom of the Australian taipan snake Oxyuranus
      scutellatus, has been previously regarded as a specific blocker of high threshold
      Ca2+ channels in heart. Here we show that taicatoxin (in contrast to a range of
      other Ca2+ channel blockers) interacts with apamin-sensitive, small conductance,
      Ca2+-activated potassium channels on both chromaffin cells and in the brain.
      Taicatoxin displays high affinity recognition of 125I-apamin acceptor-binding
      sites, present on rat synaptosomal membranes (Ki = 1.45 +/- 0.22 nM) and also
      specifically blocks affinity-labeling of a 33-kDa 125I-apamin-binding polypeptide
      on rat brain membranes. Taicatoxin (50 nM) completely blocks apamin-sensitive
      after-hyperpolarizing slow tail K+ currents generated in rat chromaffin cells
      (mean block 97 +/- 3%, n = 12) while only partially reducing total voltage
      dependent Ca2+ currents (mean block 12 +/- 4%, n = 6). In view of these findings,
      the use of taicatoxin as a specific ligand for Ca2+ channels should now be
      reconsidered.

PMID- 9242660
TI  - The three-dimensional structure of recombinant leech-derived tryptase inhibitor
      in complex with trypsin. Implications for the structure of human mast cell
      tryptase and its inhibition.
AB  - The x-ray crystal structure of recombinant leech-derived tryptase inhibitor
      (rLDTI) has been solved to a resolution of 1.9 A in complex with porcine trypsin.
      The nonclassical Kazal-type inhibitor exhibits the same overall architecture as
      that observed in solution and in rhodniin. The complex reveals structural aspects
      of the mast cell proteinase tryptase. The conformation of the binding region of
      rLDTI suggests that tryptase has a restricted active site cleft. The basic amino
      terminus of rLDTI, apparently flexible from previous NMR measurements, approaches
      the 148-loop of trypsin. This loop has an acidic equivalent in tryptase,
      suggesting that the basic amino terminus could make favorable electrostatic
      interactions with the tryptase molecule. A series of rLDTI variants constructed
      to probe this hypothesis confirmed that the amino-terminal Lys-Lys sequence plays
      a role in inhibition of human lung tryptase but not of trypsin or chymotrypsin.
      The location of such an acidic surface patch is in accordance with the known low
      molecular weight inhibitors of tryptase.

PMID- 9242661
TI  - Structure-based design of a potent chimeric thrombin inhibitor.
AB  - Using the three-dimensional structures of thrombin and the leech-derived tryptase
      inhibitor (LDTI), which does not inhibit thrombin, we were able to construct
      three LDTI variants inhibiting thrombin. Trimming of the inhibitor reactive site
      loop to fit thrombin's narrow active site cleft resulted in inhibition constants
      (Ki) in the 10 nM concentration range; similar values were obtained by the
      addition of an acidic C-terminal peptide corresponding to hirudin's tail to LDTI.
      Combination of both modifications is additive, resulting in very strong
      inhibition of thrombin (Ki in the picomolar range). On the one hand, these
      results confirm the significance of the restricted active site cleft of thrombin
      in determining its high cleavage specificity; on the other, they demonstrate that
      sufficient binding energy at the fibrinogen recognition exosite can force
      thrombin to accept otherwise unfavorable residues in the active site cleft. The
      best inhibitor thus obtained is as effective as hirudin in plasma-based clotting
      assays.

PMID- 9242662
TI  - Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart
      and kidney.
AB  - In this report we investigate the molecular mechanisms that contribute to tissue
      damage following ischemia and ischemia coupled with reperfusion
      (ischemia/reperfusion) in the rat heart and kidney. We observe the activation of
      three stress-inducible mitogen-activated protein (MAP) kinases in these tissues:
      p38 MAP kinase and the 46- and 55-kDa isoforms of Jun N-terminal kinase (JNK46
      and JNK55). The heart and kidney show distinct time courses in the activation of
      p38 MAP kinase during ischemia but no activation of either JNK46 or JNK55. These
      two tissues also respond differently to ischemia/reperfusion. In the heart we
      observe activation of JNK55 and p38 MAP kinase, whereas in the kidney all three
      kinases are active. We also examined the expression pattern of two stress
      responsive genes, c-Jun and ATF3. Our results indicate that in the heart both
      genes are induced by ischemia and ischemia/reperfusion. However, in the kidney c
      Jun and ATF3 expression is induced only by ischemia/reperfusion. To correlate
      these molecular events with tissue damage we examined DNA laddering, a common
      marker of apoptosis. A significant increase in DNA laddering was evident in both
      heart and kidney following ischemia/reperfusion and correlated with the pattern
      of kinase activation, supporting a link between stress kinase activation and
      apoptotic cell death in these tissues.

PMID- 9242663
TI  - Adaptive regulation of the cationic amino acid transporter-1 (Cat-1) in Fao
      cells.
AB  - The regulation of the high affinity cationic amino acid transporter Cat-1 in Fao
      rat hepatoma cells by amino acid availability has been studied. Cat-1 mRNA level
      increased (3-fold) in 4 h in response to amino acid starvation and remained high
      for at least 24 h. This induction was independent of the presence of serum in the
      media and transcription and protein synthesis were required for induction to
      occur. When Fao cells were shifted from amino acid-depleted media to amino acid
      fed media, the levels of the induced cat-1 mRNA returned to the basal level. In
      amino acid-fed cells, accumulation of cat-1 mRNA was dependent on protein
      synthesis, indicating that a labile protein is required to sustain cat-1 mRNA
      level. No change in the transcription rate of the cat-1 gene during amino acid
      starvation was observed, indicating that cat-1 is regulated at a post
      transcriptional step. System y+ mediated transport of arginine was reduced by 50%
      in 1 h and by 70% in 24 h after amino acid starvation. However, when 24-h amino
      acid-starved Fao cells were preloaded with 2 mM lysine or arginine for 1 h prior
      to the transport assays, arginine uptake was trans-stimulated by 5-fold. This
      stimulation was specific for cationic amino acids, since alanine, proline, or
      leucine had no effect. These data lead to the hypothesis that amino acid
      starvation results in an increased cat-1 mRNA level to support synthesis of
      additional Cat-1 protein. The following lines of evidence support the hypothesis:
      (i) the use of inhibitors of protein synthesis in starved cells inhibits the
      trans-zero transport of arginine; (ii) cells starved for 1-24 h exhibited an
      increase of trans-stimulated arginine transport activity for the first 6 h and
      had no loss of activity at 24 h, suggesting that constant replenishment of the
      transporter protein occurs; (iii) immunofluorescent staining of 24-h fed and
      starved cells for cat-1 showed similar cell surface distribution; (iv) new
      protein synthesis is not required for trans-stimulation of arginine transport
      upon refeeding of 24-h starved cells. We conclude that the increased level of cat
      1 mRNA in response to amino acid starvation support the synthesis of Cat-1
      protein during starvation and increased amino acid transport upon substrate
      presentation. Therefore, the cat-1 mRNA content is regulated by a
      derepression/repression mechanism in response to amino acid availability. We
      propose that the amino acid-signal transduction pathway consists of a series of
      steps which include the post-transcriptional regulation of amino acid transporter
      genes.

PMID- 9242664
TI  - Processing of prothyrotropin-releasing hormone by the family of prohormone
      convertases.
AB  - The post-translational processing of prothyrotropin-releasing hormone (pro-TRH25
      255) has been extensively studied in our laboratory, and the processing pathway
      to mature TRH has been elucidated. We have also demonstrated that recombinant PC1
      and PC2 process partially purified pro-TRH to cryptic peptides in vitro and that
      pro-TRH and PC1 mRNAs are coexpressed in primary cultures of hypothalamic
      neurons. To further define the role of each convertase, and particularly PC1 and
      PC2, in pro-TRH processing, recombinant vaccinia viruses were used to coexpress
      the prohormone convertases PC1, PC2, PACE4, PC5-B, furin, or control dynorphin
      together with rat prepro-TRH in constitutively secreting LoVo cells or in the
      regulated endocrine GH4C1 cell line. Radioimmunoassays from LoVo-derived secreted
      products indicated that furin cleaves the precursor to generate both N- and C
      terminal intermediates. PC1, PC2, and PACE4 only produced N-terminal
      intermediates, but less efficiently than furin. In GH4C1 cells, PC1, PC2, furin,
      PC5-B, and PACE4 produced both N-terminal and C-terminal forms. Significantly,
      TRH-Gly and TRH were mostly produced by PC1, PC2, and furin. Utilizing gel
      electrophoresis to further analyze the cleavage specificities of PC1 and PC2, we
      found that PC1 seems primarily responsible for cleavage to both intermediates and
      mature TRH, since it generated all products at significantly higher levels than
      PC2. The addition of 7B2 to the coinfection did not augment the ability of PC2 to
      cleave pro-TRH to either N- or C-terminal forms.

PMID- 9242665
TI  - Redox modulation of iron regulatory proteins by peroxynitrite.
AB  - Expression of several proteins of higher eukaryotes is post-transcriptionally
      regulated by interaction of iron-responsive elements (IREs) on their mRNAs and
      iron regulatory proteins (IRP1 and IRP2). IRP1 is a redox-sensitive iron-sulfur
      protein whose regulatory activity is modulated by iron depletion, synthesis of
      nitric oxide, or oxidative stress. IRP2 is closely related to IRP1, but it does
      not possess a [Fe-S] cluster. IRP2 is also regulated by intracellular iron level,
      but it is assumed that regulation is achieved by accelerated turn-over. In this
      report, the effect of peroxynitrite, a strong oxidant produced when nitric oxide
      and O-2 are biosynthesized simultaneously, on the RNA binding activity of IRP1
      and IRP2 was investigated in vitro. Macrophage cytosolic extracts were exposed
      directly to a bolus addition of peroxynitrite or to SIN-1, which releases a
      continuous flux of peroxynitrite. Under these two experimental conditions, IRP1
      lost its aconitase activity but did not gain increased capacity to bind IRE.
      However, addition of low amounts of the disulfide-reducing agent 2-ME during the
      binding assay revealed formation of a complex between IRP1 and IRE. Substrates of
      aconitase, which bind to the cluster of IRP1, prevented this effect, pointing to
      the [Fe-S] cluster as the target of peroxynitrite. Moreover, single mutation of
      the redox active Cys437 precluded oxidation of human recombinant IRP1 by SIN-1.
      Collectively, these results imply that peroxynitrite predisposes IRP1 to bind
      IREs under a suitable reducing environment. It is assumed that in addition to
      disrupting the cluster peroxynitrite also promotes disulfide bridge(s) between
      proximal cysteine residues in the vicinity of the IRE-binding domain, in
      particular Cys437. When exposed to peroxynitrite, IRP2 lost its spontaneous IRE
      binding activity, which was restored by further exposure to 2-mercaptoethanol,
      thus showing that peroxynitrite can also regulate IRP2 by a post-translational
      event.

PMID- 9242666
TI  - A covalent enzyme-substrate adduct in a mutant hen egg white lysozyme (D52E).
AB  - A mutant hen egg white lysozyme, D52E, was designed to correspond to the
      structure of the mutant T4 lysozyme T26E (Kuroki, R., Weaver, L. H., and Matthews
      B. W. (1993) Science 262, 2030-2033) to investigate the role of the catalytic
      residue on the alpha-side of the saccharide in these enzymes. The D52E mutant
      forms a covalent enzyme-substrate adduct, which was detected by electron ion
      spray mass spectrometry. X-ray crystallographic analysis showed that the covalent
      adduct was formed between Glu-52 and the C-1 carbon of the N-acetylglucosamine
      residue in subsite D of the saccharide binding site. It suggests that the
      catalytic mechanism of D52E mutant lysozyme proceeds through a covalent enzyme
      substrate intermediate indicating a different catalytic mechanism from the wild
      type hen egg white lysozyme. It was confirmed that the substitution of Asp-52
      with Glu is structurally and functionally equivalent to the substitution of Thr
      26 with Glu in T4 lysozyme. Although the position of the catalytic residue on the
      beta-side of the saccharide is quite conserved among hen egg white lysozyme,
      goose egg white lysozyme, and T4 phage lysozyme, the adaptability of the side
      chain on the alpha-side of the saccharide is considered to be responsible for the
      functional variation in their glycosidase and transglycosidase activities.

PMID- 9242667
TI  - Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in
      cell type-specific signal transduction.
AB  - Leukemia inhibitory factor (LIF) induces a variety of disparate biological
      responses in different cell types. These responses are thought to be mediated
      through the functional LIF receptor (LIFR), consisting of a heterodimeric complex
      of LIFR alpha-chain (LIFRalpha) and gp130. The present study investigated the
      relative capacity of the cytoplasmic domains of each receptor subunit to signal
      particular responses in several cell types. To monitor the signaling potential of
      LIFRalpha and gp130 individually, we constructed chimeric receptors by linking
      the extracellular domain of granulocyte colony-stimulating factor receptor
      (GCSFR) to the transmembrane and cytoplasmic regions of either LIFRalpha or
      gp130. Both chimeric receptors and the full-length GCSFR in expressed in M1
      myeloid leukemic cells to measure differentiation induction, in embryonic stem
      cells to measure differentiation inhibition, and in Ba/F3 cells to measure cell
      proliferation. Our results demonstrated that whereas GCSFR-gp130 receptor
      homodimer mediated a GCSF-induced signal in all three cell types, the GCSFR
      LIFRalpha receptor homodimer was only functional in embryonic stem cells. These
      findings suggest that the signaling potential of gp130 and LIFRalpha cytoplasmic
      domains may differ depending upon the tissue and cellular response initiated.

PMID- 9242668
TI  - Characterization of delta, kappa, and mu human opioid receptors overexpressed in
      baculovirus-infected insect cells.
AB  - The cDNAs encoding human delta (hDOR), kappa (hKOR) and micro (hMOR) opioid
      receptors were cloned in the baculovirus Autographa californica (AcMNPV) under
      the control of the polyhedrin promoter with or without an amino-terminal
      hexahistidine tag. Expression levels were optimized in Spodoptera frugiperda
      (Sf9) cells and were in the following order hMOR > hDOR > hKOR. The receptors
      bound antagonists with affinity values similar to those published previously for
      the receptors expressed in mammalian cells. They also retained selectivity toward
      specific antagonists. The three receptors bound peptidic agonists with low
      affinity, suggesting that they might not be functionally coupled to intracellular
      effectors. Introduction of an amino-terminal hexahistidine tag decreased the
      levels of expression markedly. Only hMOR-his was expressed at a level allowing
      binding study, but no difference could be detected in the affinities of both
      agonists and antagonists compared with the nontagged protein. hMOR expression was
      also optimized in High Five cells leading to a further increase in protein
      production. The pharmacological profile was similar to the one obtained when the
      receptor was expressed in Sf9 cells. Our results show that the baculovirus
      expression system is suitable for large scale production of human opioid
      receptors.

PMID- 9242670
TI  - Cell density-dependent apoptosis in HL-60 cells, which is mediated by an unknown
      soluble factor, is inhibited by transforming growth factor beta1 and
      overexpression of Bcl-2.
AB  - We report a novel mode of apoptosis induction observed in human leukemic HL-60
      cells. These cells spontaneously underwent apoptosis in the course of
      proliferation when the cell density became higher than 1 x 10(6)/ml. This
      occurred under ordinary in vitro culture conditions, with or without fetal calf
      serum. Even the low density cells were committed to undergo apoptosis if they
      were cultured under artificially concentrated conditions. Replacement of the
      culture supernatant of the low density cells by that of the high density ones
      resulted in apoptosis induction in the former cells. This apoptosis-inducing
      activity of the high density cell culture supernatant was completely eliminated
      by the action of trypsin but was fully restored following ultrafiltration by 3
      kDa pore-sized membrane. A strong apoptosis-inducing activity was recovered from
      the culture supernatant of the high density HL-60 cells at a specific fraction in
      reverse-phase column chromatography. Neither an interleukin-beta converting
      enzyme inhibitor nor CPP-32 inhibitor blocked the induction of cell density
      dependent apoptosis in HL-60 cells, although overexpression of Bcl-2 protein
      markedly attenuated the induction of this mode. Surprisingly, transforming growth
      factor-beta1 and activin A did not induce but, rather, inhibited the induction of
      cell density-dependent apoptosis. These data suggest that HL-60 cells release an
      unknown low molecular weight peptide-containing factor in response to an increase
      in cell density to induce apoptosis in an autocrine manner and that the
      interleukin-beta converting enzyme-independent intracellular machinery for this
      mode of apoptosis is strongly affected by signaling events through the
      transforming growth factor-beta1 receptor and by the action of Bcl-2 oncoprotein.

PMID- 9242669
TI  - A novel protein, Psp1, essential for cell cycle progression of
      Schizosaccharomyces pombe is phosphorylated by Cdc2-Cdc13 upon entry into G0-like
      stationary phase of cell growth.
AB  - A novel gene, psp1(+), which functionally complements a temperature-sensitive
      mutant defective in cell cycle progression both in G1/S and G2/M has been
      isolated from the genomic and cDNA libraries of Schizosaccharomyces pombe.
      Disruption of this gene is lethal for cell growth at 30 degrees C indicating that
      it is an essential gene for vegetative cell growth. Western analysis of the
      protein by polyclonal antibody made from glutathione S-transferase-Psp1 fusion
      protein indicated that the Psp1 protein exists in two different molecular weight
      forms depending on the growth state of the cell. In vitro experiments with a
      phosphatase showed that this difference is due to phosphorylation. The
      dephosphorylated form of the protein is dominant in actively growing cells
      whereas the phosphorylated form becomes the major species when cells enter the
      stationary phase. The Cdc2-Cdc13 complex is shown to phosphorylate the GST-Psp1
      fusion protein in vitro, and site-directed mutagenesis and phosphoamino acid
      analysis indicated that the serine residue at position 333 in the carboxyl
      terminal region is required for phosphorylation. In situ fluorescein
      isothiocyanate-conjugated antibody staining showed that this protein tends to be
      localized to both ends of the cell upon entry into the stationary phase of cell
      growth. However, overexpression of the novel protein Psp1 in actively growing
      cells inhibits cell growth causing accumulation of DNA (4n or 8n). Thus we
      speculate that Psp1 can function at both G1/S and G2/M phases complementing the
      defect of the new mutant we have isolated. It is likely that Psp1 is required
      both for proper DNA replication and for the process of mitosis.

PMID- 9242671
TI  - Multiplicity of the beta form of the cAMP-dependent protein kinase inhibitor
      protein generated by post-translational modification and alternate translational
      initiation.
AB  - Two distinct species of the thermostable inhibitor of the cAMP-dependent protein
      kinase, PKIalpha and PKIbeta, exist that are the products of separate genes. The
      PKIbeta form, as first isolated from rat testis, is a 70-amino acid protein, but
      the genomic sequence suggested that an alternate form might exist, arising as a
      consequence of alternate translational initiation. This species, now termed
      PKIbeta-78, has been synthesized by bacterial expression, demonstrated to be
      equipotent with PKIbeta-70, and also now demonstrated to occur in vivo. By
      Western blot analyses, six additional species of PKIbeta are also evident in
      tissues. Two of these represent the phospho forms of PKIbeta-78 and PKIbeta-70.
      The other four represent phospho and dephospho forms of two higher molecular mass
      PKIbeta species. These latter forms are currently termed PKIbeta-X and PKIbeta-Y,
      awaiting the full elucidation of their molecular identity. In adult rat testis
      and cerebellum, PKIbeta-70, PKIbeta-X, and PKIbeta-Y constitute 39, 23, and 32%
      and 15, 29, and 54% of the total tissue levels, respectively. In adult rat
      testis, 35-42% of each of these three species is present as a monophospho form,
      whereas no phosphorylation of them is evident in cerebellum. PKIbeta-78 is
      present at much lower levels in both rat testis and cerebellum (approximately 6
      and 2% of the total, respectively) and almost entirely as a monophospho species.
      PKIbeta-78, like PKIbeta-70, is a high affinity and specific inhibitor of the
      cAMP-dependent protein kinase. PKIbeta-Y and PKIbeta-X, in contrast, also
      significantly inhibit the cGMP-dependent protein kinase.

PMID- 9242672
TI  - Specific testicular cellular localization and hormonal regulation of the PKIalpha
      and PKIbeta isoforms of the inhibitor protein of the cAMP-dependent protein
      kinase.
AB  - We have previously demonstrated that there exist two distinct genes for the
      thermostable inhibitor protein of the cAMP-dependent protein kinase, PKIalpha and
      PKIbeta (Van Patten, S. M., Howard, P., Walsh, D. A., and Maurer, R. A. (1992)
      Mol. Endocrinol. 6, 2114-2122). We have also shown that in the testis, at least
      eight forms of PKIbeta exist, differing as a result of at least post
      translational modification and alternate translational initiation (Kumar, P., Van
      Patten, S. M., and Walsh, D. A. (1997) J. Biol. Chem. 272, 20011-20020). We now
      report that in the testis, there is a unique cellular distribution of protein
      kinase inhibitor forms, with PKIbeta being essentially (if not exclusively) a
      germ cell protein and PKIalpha being expressed primarily in Sertoli cells.
      Furthermore, there is a progressive change in the forms of PKIbeta that are
      present within germ cells with development that is initiated in testis tubules
      and continues as the germ cells migrate through the epididymis. These conclusions
      are derived from studies with isolated cell populations and with the at/at germ
      cell-deficient mouse line, by in situ hybridization, and by following the
      developmental expression of these proteins in both testis and epididymis. We have
      also shown that follicle-stimulating hormone (FSH) can increase the expression of
      both PKIalpha and PKIbeta. The FSH-regulated expression of PKIalpha in the
      Sertoli cell likely occurs via the normal route of second messenger signal
      transduction. In contrast, the FSH-dependent PKIbeta expression must arise by
      some form of Sertoli cell-germ cell intercommunication.

PMID- 9242673
TI  - Globin gene silencing in primary erythroid cultures. An inhibitory role for
      interleukin-6.
AB  - There are numerous similarities between the erythroid and megakaryocytic lineages
      which suggest that commitment to either lineage occurs relatively late in
      hematopoiesis. Commitment toward megakaryocyte development requires obligatory
      silencing of erythroid-specific genes. Therefore, we investigated the effects of
      interleukin-6, a known inducer of thrombocyte production, on globin gene
      expression during erythroid differentiation. Studies in K562 cells demonstrated
      inhibition of gamma globin gene mRNA production and chain biosynthesis in the
      presence of exogenous interleukin-6 which was abrogated by anti-interleukin-6
      monoclonal antibody. Similar studies in primary erythroid progenitors showed
      inhibition of burst-forming unit-erythroid colony formation when interleukin-6
      was added late in cultures with decreased gamma and beta globin gene mRNA
      production. Protein binding studies demonstrated an increase in activator protein
      1 binding to its consensus sequence by 24 h of interleukin-6 treatment.
      Inhibition of activator protein-1 gene activity had no effect on gamma gene
      silencing by interleukin-6. A potential interleukin-6 response element was
      identified in the gamma globin gene. Interleukin-6 treatment led to a rapid
      increase in protein binding to the target DNA sequence. These results suggest
      that interleukin-6 may play an important role in globin gene silencing during
      megakaryocytic lineage commitment.

PMID- 9242674
TI  - Protein-tyrosine phosphatase SHP-1 is dispensable for FcgammaRIIB-mediated
      inhibition of B cell antigen receptor activation.
AB  - The inhibitory Fc receptor, FcgammaRIIB, provides a signal that aborts B cell
      antigen receptor activation, blocking extracellular calcium influx. Because the
      protein-tyrosine phosphatase SHP-1 binds tyrosyl phosphorylated FcgammaRIIB and
      FcgammaRIIB-mediated inhibition is defective in motheaten (me/me) mice, which do
      not express SHP-1, it was proposed that SHP-1 mediates FcgammaRIIB signaling in B
      cells (D'Ambrosio, D., Hippen, K. L., Minskoff, S. A., Mellman, I., Pani, G.,
      Siminovitch, K. A., and Cambier, J. C. (1995) Science 268, 293-297). However, SHP
      1 is dispensable for FcgammaRIIB-mediated inhibition of FcepsilonRI signaling in
      mast cells (Ono, M., Bolland, S., Tempst, P., and Ravetch, J. V. (1996) Nature
      383, 263-266), prompting us to re-examine the role of SHP-1 in FcgammaRIIB
      signaling in B cells. We generated immortalized sIgM+, FcgammaRIIB+ cell lines
      from me/me mice and normal littermates. Co-ligation of FcgammaRIIB and the sIgM
      antigen receptor inhibits calcium influx in both cell lines. Inhibition is
      reversed by preincubation with anti-FcgammaRIIB antibodies, indicating that it is
      mediated by FcgammaRIIB. The inositol 5' phosphatase SHIP is recruited to tyrosyl
      phosphorylated FcgammaRIIB in both cell lines. FcgammaRIIB-mediated CD19
      dephosphorylation also occurs in the presence or the absence of SHP-1. Our
      results establish that SHP-1 is dispensable for FcgammaRIIB-mediated inhibition
      of sIgM antigen receptor signaling.

PMID- 9242675
TI  - Dimerization of the N-terminal amphipathic alpha-helix domain of the fungal
      immunomodulatory protein from Ganoderma tsugae (Fip-gts) defined by a yeast two
      hybrid system and site-directed mutagenesis.
AB  - A fungal immunomodulatory protein (Fip-gts) was purified from Ganoderma tsugae.
      The DNA encoding Fip-gts was isolated from a cDNA library of G. tsugae by reverse
      transcriptase-polymerase chain reaction. The complete amino acid sequence of Fip
      gts, deduced from the nucleotide sequence of the cDNA, was the same as LZ-8
      isolated from Ganodermn lucidum. Recombinant Fip-gts was expressed as a
      glutathione S-transferase fusion protein in Escherichia coli with a yield of 20
      mg/liter of culture. Recombinant Fip-gts, purified to homogeneity, had the same
      blast formation stimulatory activity to human peripheral blood lymphocytes as
      native Fip-gts. The yeast two-hybrid system and site-directed mutagenesis were
      used to determine whether dimerization of Fip-gts occurred. Deletion analysis of
      the N-terminal amphipathic alpha-helix domain of Fip-gts identified a sequence of
      about 10 amino acids responsible for inducing immunomodulatory activity. Non
      functional Fip-gts deletion mutants did not form dimers, whereas wild type Fip
      gts did as determined by gel filtration. A mutant with deletions at Leu-5, Phe-7,
      and Leu-9 lost the amphipathic characteristics of the N-terminal domain and the
      ability to form dimers as well as its immunomodulatory activity. Fusion of Fip
      gts with the DNA binding and the transactivation domains of GAL4 resulted in the
      activation of the lacZ activator gene, indicating the interaction of Fip-gts with
      it itself. The dimerization domain was further defined by analyzing the ability
      of the N-terminal 13 amino acids or Leu-5, Phe-7, and Leu-9 deletion mutants of
      Fip-gts to interact with the wild type Fip-gts. These experiments confirmed the N
      terminal amphipathic alpha-helix as the dimerization domain and suggest that the
      dimerization of Fip-gts may play an important role in Fip-gts immunomodulatory
      activity.

PMID- 9242676
TI  - Transcriptional coactivator p300 stimulates cell type-specific gene expression in
      cardiac myocytes.
AB  - Terminal differentiation is characterized by cell cycle arrest and the expression
      of cell type-specific genes. Previous work has suggested that the p300 family of
      transcriptional coactivators plays an important role in preventing the re
      initiation of DNA synthesis in terminally differentiated cardiac myocytes. In
      this study, we investigated whether p300 proteins are also involved in the
      transcriptional activation of cell type-specific genes in these cells. Since p300
      function can be abrogated through direct binding by the adenovirus E1A protein,
      we overexpressed E1A in cardiac myocytes using recombinant adenoviral vectors.
      The expression of transfected reporter genes driven by alpha- or beta-myosin
      heavy chain promoters was markedly diminished by expression of the 12 S E1A
      protein. In contrast, the activity of a promoter derived from the ubiquitously
      expressed beta-actin gene was affected only modestly. While an E1A mutant unable
      to bind members of the retinoblastoma family of pocket proteins decreased the
      activity of alpha- and beta-myosin heavy chain promoters to nearly the same
      extent as wild type 12 S E1A, transcriptional repression by a mutant defective
      for p300 binding was severely impaired. Furthermore, overexpression of p300 and,
      to an even greater extent, p300del33, a mutant lacking residues required for
      binding by E1A, relieved E1A's repression of beta-myosin heavy chain promoter
      activity while having no effect on the activity of the beta-actin promoter. Thus,
      E1A's transcriptional repression of cell type-specific genes in cardiac myocytes
      is mediated through its binding of p300 proteins, and these proteins appear to be
      involved in maintaining both cell type-specific gene expression and cell cycle
      arrest in cardiac myocytes.

PMID- 9242677
TI  - Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor
      1.
AB  - Transferrin (Tf) is a liver-derived iron transport protein whose plasma
      concentration increases following exposure to hypoxia. Here, we present a cell
      culture model capable of expressing Tf mRNA in an oxygen-dependent manner. A 4
      kilobase pair Tf promoter/enhancer fragment as well as the 300-base pair liver
      specific Tf enhancer alone conveyed hypoxia responsiveness to a heterologous
      reporter gene construct in hepatoma but not HeLa cells. Within this enhancer, a
      32-base pair hypoxia-responsive element was identified, which contained two
      hypoxia-inducible factor-1 (HIF-1) binding sites (HBSs). Mutation analysis showed
      that both HBSs function as oxygen-regulated enhancers in Tf-expressing as well as
      in non-Tf-expressing cell lines. Mutation of both HBSs was necessary to
      completely abolish hypoxic reporter gene activation. Transient co-expression of
      the two HIF-1 subunits HIF-1alpha and aryl hydrocarbon receptor nuclear
      translocator (ARNT)/HIF-1beta resulted in enhanced reporter gene expression even
      under normoxic conditions. Overexpression of a dominant-negative ARNT/HIF-1beta
      mutant reduced hypoxic activation. DNA binding studies using nuclear extracts
      from the mouse hepatoma cell line Hepa1 and the ARNT/HIF-1beta-deficient subline
      Hepa1C4, as well as antibodies raised against HIF-1alpha and ARNT/HIF-1beta
      confirmed that HIF-1 binds the Tf HBSs. Mutation analysis and competition
      experiments suggested that the 5' HBS was more efficient in binding HIF-1 than
      the 3' HBS. Finally, hypoxic induction of endogenous Tf mRNA was abrogated in
      Hepa1C4 cells, confirming that HIF-1 confers oxygen regulation of Tf gene
      expression by binding to the two HBSs present in the Tf enhancer.

PMID- 9242678
TI  - Adrenocorticotropin induction of stress-activated protein kinase in the adrenal
      cortex in vivo.
AB  - A broad array of stressors induce ACTH release from the anterior pituitary, with
      consequent stimulation of the adrenal cortex and release of glucocorticoids
      critical for survival of the animal. ACTH stimulates adrenocortical gene
      expression in vivo and inhibits adrenocortical cell proliferation. Binding of
      ACTH to its G-protein-coupled receptor stimulates the production of cAMP and
      activation of the protein kinase A pathway. The stress-activated protein kinases
      (SAPKs) (or c-Jun N-terminal kinases) and the extracellular signal-regulated
      kinases (ERKs) are members of the mitogen-activated protein kinase family of
      serine/threonine kinases, which have recently been implicated in G-protein
      coupled receptor intracellular signaling. The SAPKs are preferentially induced by
      osmotic stress and UV light, whereas the ERKs are preferentially induced by
      growth factors and proliferative signals in cultured cells. In these studies,
      ACTH stimulated SAPK activity 3-4-fold both in the adrenal cortex in vivo and in
      the Y1 adrenocortical cell line. 12-O-Tetradecanoylphorbol-13-acetate but not
      cAMP induced SAPK activity in Y1 cells. The isoquinolinesulfonamide inhibitors H
      8 and H-89 blocked ACTH induction of SAPK activity at protein kinase C inhibitory
      doses but not at protein kinase A inhibitory doses. The calcium chelating agent
      EGTA inhibited ACTH-induced SAPK activity and the calcium ionophore A23187
      induced SAPK activity 3-fold. In contrast with the induction of SAPK by ACTH, ERK
      activity was inhibited in the adrenal cortex in vivo and in Y1 adrenal cells.
      Together these findings suggest that ACTH induces SAPK activity through a PKC and
      Ca+2-dependent pathway. The induction of SAPK and inhibition of ERK by ACTH in
      vivo may preferentially regulate target genes involved in the adrenocortical
      stress responses in the whole animal.

PMID- 9242679
TI  - Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the
      interferon-alpha-stimulated transcription factor ISGF3.
AB  - Cells express a variety of STAT (signal transducer and activator of
      transcription) transcription factors that are structurally homologous and yet
      function specifically in response to particular cytokines. The functions of the
      individual STATs are dependent on distinct protein-protein interactions. STAT1
      and STAT2 are activated by tyrosine phosphorylation in response to type I
      interferons-alpha/beta (IFN-alpha/beta) and subsequently form a multimeric
      transcription factor designated the IFN-alpha-stimulated gene factor 3 (ISGF3).
      ISGF3 is a unique STAT complex because it also contains a non-STAT molecule, p48,
      which is a critical DNA-binding component. We provide evidence that STAT2
      specifically interacts with p48 in vivo before and after IFN-alpha stimulation.
      The specificity of ISGF3 formation is therefore a result of the distinct nature
      of the STAT2 molecule. Coimmunoprecipitation assays demonstrate p48 association
      with STAT2 but not STAT1. Hybrid STAT2. STAT1 molecules were used to identify a
      region of STAT2 which specifically associates with p48. The region of STAT2
      interaction spans an amino-terminal region of two predicted coiled coils. The
      studies demonstrate the in vivo existence of a STAT2.p48 complex and a distinct
      STAT2.STAT1 complex after IFN-alpha stimulation. Data suggest that distinct
      bipartite complexes STAT2.p48 and STAT2.STAT1 translocate to the nucleus and
      associate on the DNA target site as ISGF3.

PMID- 9242680
TI  - Riboflavin 5'-hydroxymethyl oxidation. Molecular cloning, expression, and
      glycoprotein nature of the 5'-aldehyde-forming enzyme from Schizophyllum commune.
AB  - Vitamin B2-aldehyde-forming enzyme catalyzes oxidation of the 5'-hydroxymethyl of
      riboflavin to the formyl group. We have purified the enzyme from the culture
      media of Schizophyllum commune (ATCC 38719) by modifying the procedure of
      Tachibana and Oka (Tachibana, S., and Oka, M. (1981) J. Biol. Chem. 256, 6682
      6685) for cell-free extract. By SDS-polyacrylamine gel electrophoresis, the
      enzyme appears to be 78 kDa. The enzyme has a blocked amino terminus, so
      fragments were obtained by cleaving the purified enzyme with lysyl endopeptidase.
      Selected peptides were sequenced from their amino termini. We have isolated a
      full-length cDNA clone using a DNA hybridization probe amplified by polymerase
      chain reaction with two degenerate oligonucleotide primers, the design of which
      was based on one of the partial amino acid sequences. From the cDNA clone, it is
      evident that the enzyme has a Ser/Thr-rich fragment near the COOH-terminal Asp.
      The enzyme was determined to be a glycoprotein; however, O-deglucosylation only
      slightly affects activity. Computer searches showed that the B2-aldehyde-forming
      enzyme has little homology with other proteins, but domain motifs may reflect N
      myristoylation of a dehydrogenase with a signature similar to 4Fe-4S ferredoxins.
      The enzyme cDNA was subcloned into a Pichia expression vector pPIC9K to produce a
      recombinant protein which exhibited B2-aldehyde-forming enzyme activity.

PMID- 9242681
TI  - In vitro analysis of the stop-transfer process during translocation across the
      cytoplasmic membrane of Escherichia coli.
AB  - In this study, using a derivative of proOmpA containing an artificial stop
      transfer sequence (proOmpA2xH1), we analyzed the process of stop-transfer during
      translocation across the cytoplasmic membrane of Escherichia coli. ProOmpA2xH1
      did not interfere with the transit of wild-type proOmpA. When proOmpA2xH1 was
      anchored in the membrane, membrane-inserted SecA was deinserted with the
      reversion of the inverted topology of SecG. Cross-linking experiments revealed
      that the anchored proOmpA2xH1 that does not interact with either SecY or SecA.
      These results, taken together, suggest that proOmpA2xH1 leaves the translocation
      pathway by means of a specific interaction between the stop-transfer sequence and
      the translocational channel.

PMID- 9242682
TI  - A dual involvement of the amino-terminal domain of ezrin in F- and G-actin
      binding.
AB  - Human recombinant ezrin, or truncated forms, were coated in microtiter plate and
      their capacity to bind actin determined. F-actin bound ezrin with a Kd of 504 +/-
      230 nM and a molecular stoichiometry of 10.6 actin per ezrin. Ezrin bound both
      alpha- and beta/gamma-actin essentially as F-form. F-actin binding was totally
      prevented or drastically reduced when residues 534-586 or 13-30 were deleted,
      respectively. An actin binding activity was detected in amino-terminal constructs
      (ezrin 1-310 and 1-333) provided the glutathione S-transferase moiety of the
      fusion protein was removed. Series of carboxyl-terminal truncations confirmed the
      presence of this actin-binding site which bound both F- and G-actin. The F- and G
      actin-binding sites were differently sensitive to various chemical effectors and
      distinct specific ezrin antibodies. The internal actin-binding site was mapped
      between residues 281 and 333. The association of ezrin amino-terminal fragment to
      full-length ezrin blocked F-actin binding to ezrin. It is proposed that, in full
      length ezrin, the F-actin-binding site required the juxtaposition of the distal
      most amino- and carboxyl-terminal residues of the ezrin molecule.

PMID- 9242683
TI  - Regulation of major histocompatibility complex class I gene expression in thyroid
      cells. Role of the cAMP response element-like sequence.
AB  - The major histocompatibility complex (MHC) class I gene cAMP response element
      (CRE)-like site, -107 to -100 base pairs, is a critical component of a previously
      unrecognized silencer, -127 to -90 bp, important for thyrotropin (TSH)/cAMP
      mediated repression in thyrocytes. TSH/cAMP induced-silencer activity is
      associated with the formation of novel complexes with the 38-base pair silencer,
      whose appearance requires the CRE and involves ubiquitous and thyroid-specific
      proteins as follows: the CRE-binding protein, a Y-box protein termed thyrotropin
      receptor (TSHR) suppressor element protein-1 (TSEP-1); thyroid transcription
      factor-1 (TTF-1); and Pax-8. TTF-1 is an enhancer of class I promoter activity;
      Pax-8 and TSEP-1 are suppressors. TSH/cAMP decreases TTF-1 complex formation with
      the silencer, thereby decreasing maximal class I expression; TSH/cAMP enhance
      TSEP-1 and Pax-8 complex formation in association with their repressive actions.
      Oligonucleotides that bind TSEP-1, not Pax-8, prevent formation of the TSH/cAMP
      induced complexes associated with TSH-induced class I suppression, i.e. TSEP-1
      appears to be the dominant repressor factor associated with TSH/cAMP-decreased
      class I activity and formation of the novel complexes. TSEP-1, TTF-1, and/or Pax
      8 are involved in TSH/cAMP-induced negative regulation of the TSH receptor gene
      in thyrocytes, suppression of MHC class II, and up-regulation of thyroglobulin.
      TSH/cAMP coordinate regulation of common transcription factors may, therefore, be
      the basis for self-tolerance and the absence of autoimmunity in the face of TSHR
      mediated increases in gene products that are important for thyroid growth and
      function but are able to act as autoantigens.

PMID- 9242684
TI  - Polarity and specific sequence requirements of peroxisome proliferator-activated
      receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional
      analysis of the malic enzyme gene PPAR response element.
AB  - The malic enzyme (ME) gene is a target for both thyroid hormone receptors and
      peroxisome proliferator-activated receptors (PPAR). Within the ME promoter, two
      direct repeat (DR)-1-like elements, MEp and MEd, have been identified as putative
      PPAR response elements (PPRE). We demonstrate that only MEp and not MEd is able
      to bind PPAR/retinoid X receptor (RXR) heterodimers and mediate peroxisome
      proliferator signaling. Taking advantage of the close sequence resemblance of MEp
      and MEd, we have identified crucial determinants of a PPRE. Using reciprocal
      mutation analyses of these two elements, we show the preference for adenine as
      the spacing nucleotide between the two half-sites of the PPRE and demonstrate the
      importance of the two first bases flanking the core DR1 in 5'. This latter
      feature of the PPRE lead us to consider the polarity of the PPAR/RXR heterodimer
      bound to its cognate element. We demonstrate that, in contrast to the polarity of
      RXR/TR and RXR/RAR bound to DR4 and DR5 elements respectively, PPAR binds to the
      5' extended half-site of the response element, while RXR occupies the 3' half
      site. Consistent with this polarity is our finding that formation and binding of
      the PPAR/RXR heterodimer requires an intact hinge T region in RXR while its
      integrity is not required for binding of the RXR/TR heterodimer to a DR4.

PMID- 9242685
TI  - Hypotonic stress increases cyclooxygenase-2 expression and prostaglandin release
      from amnion-derived WISH cells.
AB  - This report examines the effect of cell volume expansion on cyclooxygenase-2 (COX
      2) mRNA expression, COX-2 protein expression, and prostaglandin E2 release from
      human amnion-derived WISH cells. Earle's balanced salts solution (EBSS) with
      limited NaCl concentration was utilized as the induction medium. COX-2 mRNA was
      elevated 6-fold in cells incubated for 1 h in hypotonic EBSS. COX-2 mRNA
      expression was not increased when raffinose or sucrose were used to reconstitute
      low NaCl. Actinomycin D blocked COX-2 mRNA increase by hypotonic stress, while
      cycloheximide enhanced COX-2 mRNA expression. COX-2 mRNA and protein
      concentrations increased as a function of decreasing media osmolarity and
      incubation time in hypotonic EBSS. Hypotonic EBSS induced a 3-fold increase in
      prostaglandin E2 release. WISH cells transiently transfected with a luciferase
      expression vector driven by the human COX-2 promoter for the COX-2 gene show a 3
      fold increase in luciferase activity when incubated in hypotonic EBSS. COX-2 mRNA
      levels in primary human amnion cells were also increased by hypotonic stress.
      This study suggests that amnion cell COX-2 gene expression is regulated by cell
      volume expansion and/or increased plasma membrane tension.

PMID- 9242686
TI  - Parathyroid hormone-dependent degradation of type II Na+/Pi cotransporters.
AB  - Parathyroid hormone (PTH) inhibits proximal tubular brush border membrane Na+/Pi
      cotransport activity; this decrease in the transport activity was found to be
      associated with a decrease in type II Na+/Pi cotransporter protein content in rat
      brush border membranes. In the present study we investigated the PTH-dependent
      regulation of the type II Na+/Pi cotransporter in opossum kidney cells, a
      previously established model to study cellular mechanisms involved in the
      regulation of proximal tubular Na+/Pi cotransport. We transfected opossum kidney
      cells with a cDNA coding for NaPi-2 (rat renal type II Na+/Pi cotransporter).
      This allowed the study of PTH-dependent regulation of the transfected NaPi-2 and
      of the corresponding intrinsic cotransporter (NaPi-4). The results show (i) that
      the intrinsic and the transfected cotransporters are functionally (transport) and
      morphologically (immunofluorescence) localized at the apical membrane, (ii) that
      the intrinsic as well as the transfected Na+/Pi cotransport activities are
      inhibited by PTH, (iii) that PTH leads to a retrieval of both cotransporters from
      the apical membrane, (iv) that both cotransporters are rapidly degraded in
      response to PTH, and (v) that the reappearance/recovery of type II Na+/Pi
      cotransporter protein and function from PTH inhibition requires de novo protein
      synthesis. These results document that PTH leads to a removal of type II Na+/Pi
      cotransporters from the apical membrane and to their subsequent degradation.

PMID- 9242687
TI  - Early growth response-1-dependent apoptosis is mediated by p53.
AB  - The early growth response-1 (EGR-1) protein is an anti-proliferative signal for
      certain tumor cells and is required for apoptosis induced by stimuli that elevate
      intracellular Ca2+. We present evidence that EGR-1 transactivates the promoter of
      the p53 gene and up-regulates p53 RNA and protein levels. Inhibition of p53
      function with dominant-negative p53 mutants abrogates EGR-1-dependent apoptosis.
      These findings establish a direct functional link between EGR-1 and the p53
      mediated cell death pathway and suggest that mutant forms of p53 in tumor cells
      may provide resistance to the anti-proliferative effects of EGR-1.

PMID- 9242688
TI  - Activity of plasma membrane-recruited Raf-1 is regulated by Ras via the Raf zinc
      finger.
AB  - Ras recruits Raf to the plasma membrane for activation by a combination of
      tyrosine phosphorylation and other as yet undefined mechanism(s). We show here
      that the Raf zinc finger is not required for plasma membrane recruitment of Raf
      by Ras but is essential for full activation of Raf at the plasma membrane.
      Membrane targeting cannot compensate for the absence of the zinc finger. One
      facet of the zinc finger activation defect is revealed using a constitutively
      activated Raf mutant. Targeting Raf Y340D,Y341D to the plasma membrane increments
      activity, but full activation requires coexpression with activated Ras. This
      sensitivity to regulation by Ras at the plasma membrane is abrogated by mutations
      in the Raf zinc finger but is unaffected by mutation of the minimal Ras binding
      domain. These data show for the first time that Ras has two separate roles in Raf
      activation: recruitment of Raf to the plasma membrane through an interaction with
      the minimal Ras binding domain and activation of membrane-localized Raf via a
      mechanism that requires the Raf zinc finger.

PMID- 9242689
TI  - Biosynthesis of archaeosine, a novel derivative of 7-deazaguanosine specific to
      archaeal tRNA, proceeds via a pathway involving base replacement on the tRNA
      polynucleotide chain.
AB  - Archaeosine is a novel derivative of 7-deazaguanosine found in transfer RNAs of
      most organisms exclusively in the archaeal phylogenetic lineage and is present in
      the D-loop at position 15. We show that this modification is formed by a
      posttranscriptional base replacement reaction, catalyzed by a new tRNA-guanine
      transglycosylase (TGT), which has been isolated from Haloferax volcanii and
      purified nearly to homogeneity. The molecular weight of the enzyme was estimated
      to be 78 kDa by SDS-gel electrophoresis. The enzyme can insert free 7-cyano-7
      deazaguanine (preQ0 base) in vitro at position 15 of an H. volcanii tRNA T7
      transcript, replacing the guanine originally located at that position without
      breakage of the phosphodiester backbone. Since archaeosine base and 7-aminomethyl
      7-deazaguanine (preQ1 base) were not incorporated into tRNA by this enzyme, preQ0
      base appears to be the actual substrate for the TGT of H. volcanii, a conclusion
      supported by characterization of preQ0 base in an acid-soluble extract of H.
      volcanii cells. Thus, this novel TGT in H. volcanii is a key enzyme for the
      biosynthetic pathway leading to archaeosine in archaeal tRNAs.

PMID- 9242690
TI  - Energetically unfavorable interactions among the zinc fingers of transcription
      factor IIIA when bound to the 5 S rRNA gene.
AB  - Xenopus transcription factor IIIA (TFIIIA) binds to over 50 base pairs in the
      internal control region of the 5 S rRNA gene, yet the binding energy for this
      interaction (DeltaG0 = -12.8 kcal/mol) is no greater than that exhibited by many
      proteins that occupy much smaller DNA targets. Despite considerable study, the
      distribution of the DNA binding energy among the various zinc fingers of TFIIIA
      remains poorly understood. By analyzing TFIIIA mutants with disruptions of
      individual zinc fingers, we have previously shown that each finger contributes
      favorably to binding (Del Rio, S., Menezes, S. R., and Setzer, D. R. (1993) J.
      Mol. Biol. 233, 567-579). Those results also suggested, however, that
      simultaneous binding by all nine zinc fingers of TFIIIA may involve a substantial
      energetic cost. Using complementary N- and C-terminal fragments and full-length
      proteins containing pairs of disrupted fingers, we now show that energetic
      interference indeed occurs between zinc fingers when TFIIIA binds to the 5 S rRNA
      gene and that the greatest interference occurs between fingers at opposite ends
      of the protein in the TFIIIA.5 S rRNA gene complex. Some, but not all, of the
      thermodynamically unfavorable strain in the TFIIIA.5 S rRNA gene complex may be
      derived from bending of the DNA that is necessary to accommodate simultaneous
      binding by all nine zinc fingers of TFIIIA. The energetics of DNA binding by
      TFIIIA thus emerges as a compromise between individual favorable contacts of
      importance along the length of the internal control region and long range strain
      or distortion in the protein, the 5 S rRNA gene, or both that is necessary to
      accommodate the various local interactions.

PMID- 9242691
TI  - GS15, a 15-kilodalton Golgi soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE) homologous to rbet1.
AB  - Bet1p plays an essential role in vesicular transport from the endoplasmic
      reticulum (ER) to the Golgi in yeast, and it functions as a vesicle soluble N
      ethylmaleimide-sensitive factor protein receptor (v-SNARE). A mammalian protein
      related to Bet1p has been reported previously and was referred to as rbet1. We
      have now identified a new mammalian protein that is homologous to rbet1 (28%
      amino acid identity). mRNA for this rbet1 homologue is widely expressed in rat
      tissues. Affinity-purified polyclonal antibodies raised against recombinant
      protein specifically recognized a 15-kilodalton integral membrane protein highly
      enriched in Golgi membranes. Indirect immunofluorescence microscopy revealed that
      this protein is specifically associated with the Golgi apparatus in diverse cell
      types. Biochemical characterization established that this protein behaves like a
      SNARE and was named GS15 (Golgi SNARE with a size of 15 kilodaltons). These
      properties raise the possibility that GS15 is a novel SNARE mediating a yet to be
      defined transport event associated with the Golgi apparatus.

PMID- 9242692
TI  - Efficient cellular transformation by the Met oncoprotein requires a functional
      Grb2 binding site and correlates with phosphorylation of the Grb2-associated
      proteins, Cbl and Gab1.
AB  - The Tpr-Met oncoprotein consists of the catalytic kinase domain of the hepatocyte
      growth factor/scatter factor receptor tyrosine kinase (Met) fused downstream from
      sequences encoded by the tpr gene. Tpr-Met is a member of a family of tyrosine
      kinase oncoproteins generated following genomic rearrangement and has
      constitutive kinase activity. We have previously demonstrated that a single
      carboxyl-terminal tyrosine residue, Tyr489, is essential for efficient
      transformation of Fr3T3 fibroblasts by Tpr-Met and forms a multisubstrate binding
      site for Grb2, phosphatidylinositol 3' kinase, phospholipase Cgamma, SHP2, and an
      unknown protein of 110 kDa. A mutant Tpr-Met protein that selectively fails to
      bind Grb2 has reduced transforming activity, implicating pathways downstream of
      Grb2 in Tpr-Met mediated cell transformation. We show here that the 110-kDa Tpr
      Met substrate corresponds to the recently identified Grb2-associated protein,
      Gab1. Moreover, we show that tyrosine phosphorylation of the Cbl protooncogene
      product as well as Gab1 required Tyr489 and correlated with the ability of Tpr
      Met to associate with Grb2 and to transform cells, providing evidence that
      pathways downstream of Gab1 and/or Cbl may play a role in Tpr-Met-mediated cell
      transformation.

PMID- 9242693
TI  - Role of TrfA and DnaA proteins in origin opening during initiation of DNA
      replication of the broad host range plasmid RK2.
AB  - The Escherichia coli protein DnaA and the plasmid RK2-encoded TrfA protein are
      required for initiation of replication of the broad host range plasmid RK2. The
      TrfA protein has been shown to bind to five 17-base pair repeat sequences,
      referred to as iterons, at the minimal replication origin (oriV). Using DNase I
      footprinting and a gel mobility shift assay, purified DnaA protein was found to
      bind to four DnaA consensus binding sequences immediately upstream of the five
      iterons at the RK2 origin of replication. Binding of the TrfA protein to the
      iterons results in localized strand opening within the A+T-rich region of the
      replication origin as determined by reactivity of the top and bottom strands to
      potassium permanganate (KMnO4). The presence of either the E. coli DnaA or HU
      protein is required for the TrfA-mediated strand opening. Although the DnaA
      protein itself did not produce an RK2 open complex, it did enhance and/or
      stabilize the TrfA-induced strand opening.

PMID- 9242694
TI  - Mutation of the protein kinase C phosphorylation site on rat alpha1 Na+,K+-ATPase
      alters regulation of intracellular Na+ and pH and influences cell shape and
      adhesiveness.
AB  - The enzyme Na+,K+-ATPase creates the transmembrane Na+ gradient that is of vital
      importance for functioning of all eukaryotic cells. Na+, K+-ATPase can be
      phosphorylated by protein kinase A (PKA) and protein kinase C (PKC), and these
      sites of phosphorylation have been identified. In the present study, we have
      examined the physiological significance of PKC phosphorylation of rat Na+,K+
      ATPase. In COS cells transfected with wild type rat Na+,K+-ATPase alpha1,
      intracellular Na+ was higher and pH was lower than in cells transfected with rat
      Na+,K+-ATPase alpha1 in which the PKC phosphorylation site, Ser-23, had been
      mutated into alanine. Phorbol dibutyrate inhibited Na+,K+-ATPase-dependent ATP
      hydrolysis and Rb+ uptake in cells expressing wild type Na+,K+-ATPase but not in
      cells expressing S23A Na+,K+-ATPase. Cells expressing the S23A mutant had a more
      rounded appearance and attached less well to fibronectin than did untransfected
      cells or cells transfected with wild type rat Na+, K+-ATPase alpha1. These
      results indicate a functional role for PKC-mediated phosphorylation of rat Na+,K+
      ATPase alpha1 and suggest a connection between this enzyme and cell adhesion.

PMID- 9242695
TI  - A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed
      by mammalian astrocytes.
AB  - Ceruloplasmin is a copper-binding protein, which is the major ferroxidase in
      plasma of hepatic origin. We now provide evidence for a novel membrane-bound form
      of ceruloplasmin expressed by astrocytes in the mammalian central nervous system.
      Using a monoclonal antibody (1A1), we show that the cell surface antigen
      recognized by this antibody is ceruloplasmin and that it is directly anchored to
      the cell surface via a glycosylphosphatidylinositol (GPI) anchor. Our peptide
      mapping and other immunochemical studies indicate that, except for the GPI
      anchor, the membrane-bound and secreted plasma forms are similar. We also show
      that the membrane-bound form of ceruloplasmin has oxidase activity. These studies
      therefore suggest that the GPI-anchored form of ceruloplasmin may play a role
      similar to the secreted form in oxidizing ferrous iron. The GPI-anchored form of
      ceruloplasmin expressed by astrocytes is likely to be the major form of this
      molecule in the central nervous system because serum ceruloplasmin does not cross
      the blood-brain barrier. Lack of this form of ceruloplasmin in the central
      nervous system could lead to the generation of highly toxic free radicals, which
      can cause neuronal degeneration as seen in aceruloplasminemia and other
      neurodegenerative diseases such as Parkinson's and Alzheimer's disease.

PMID- 9242697
TI  - Role of protein targeting to glycogen (PTG) in the regulation of protein
      phosphatase-1 activity.
AB  - We have recently cloned from 3T3-L1 adipocytes a novel glycogen-targeting subunit
      of protein phosphatase-1, termed PTG (Printen, J. A., Brady, M. J., and Saltiel,
      A. R. (1997) Science 275, 1475-1478). Differentiation of 3T3-L1 fibroblasts into
      highly insulin-responsive adipocytes resulted in a marked increase in PTG
      expression. Immobilized glutathione S-transferase (GST)-PTG fusion protein
      specifically bound either PP1 or phosphorylase a. Addition of soluble GST-PTG to
      3T3-L1 lysates increased PP1 activity against 32P-labeled phosphorylase a by
      decreasing the Km of PP1 for phosphorylase 5-fold, while having no effect on the
      Vmax of the dephosphorylation reaction. Alternatively, PTG did not affect PP1
      activity against hormone-sensitive lipase. PTG was not a direct target of
      intracellular signaling, as insulin or forskolin treatment of cells did not
      activate a kinase capable of phosphorylating PTG in vivo or in vitro. Finally,
      PTG decreased the ability of DARPP-32 to inhibit PP1 activity from 3T3-L1
      adipocyte lysates. These data cumulatively suggest that PTG increases PP1
      activity against specific proteins by several distinct mechanisms.

PMID- 9242696
TI  - Selective up-regulation of cytokine-induced RANTES gene expression in lung
      epithelial cells by overexpression of IkappaBR.
AB  - We previously reported the cloning of a cDNA for IkappaBR (for IkappaB-related)
      from human lung alveolar epithelial cells. IkappaBR is related to the IkappaB
      proteins that function as regulators of the NF-kappaB family of transcription
      factors. Here, we investigated the consequence of IkappaBR overexpression on the
      expression of NF-kappaB-regulated chemokine genes in lung alveolar epithelial
      cells. Chemokines play an important role in many inflammatory diseases such as
      asthma and AIDS. Overexpression of IkappaBR in the lung cells resulted in a rapid
      50-100-fold greater production of the RANTES (regulated upon activation, normal T
      expressed and presumably secreted) protein upon cytokine-induction compared with
      control cells. IkappaBR overexpression, however, did not enhance interleukin-8 or
      MIP-1alpha gene expression, despite the fact that the expression of all three
      chemokine genes are regulated by NF-kappaB. The up-regulation of RANTES gene
      expression resulting from overexpression of IkappaBR correlated with increased
      amounts of a unique RANTES-kappaB binding activity and decreased binding of p50
      homodimers. Previous studies have shown that p50 homodimers function as
      repressors of certain kappaB sites. Our studies suggest that IkappaBR can aid
      activation of select NF-kappaB-regulated genes by sequestering p50 homodimers.

PMID- 9242698
TI  - Replication of template-primers containing propanodeoxyguanosine by DNA
      polymerase beta. Induction of base pair substitution and frameshift mutations by
      template slippage and deoxynucleoside triphosphate stabilization.
AB  - Propanodeoxyguanosine (PdG) is a model for several unstable exocyclic adducts
      formed by reaction of DNA with bifunctional carbonyl compounds generated by lipid
      peroxidation. The effect of PdG on DNA synthesis by human DNA polymerase beta was
      evaluated using template-primers containing PdG at defined sites. DNA synthesis
      was conducted in vitro and the products were analyzed by polyacrylamide gel
      electrophoresis and DNA sequencing. The extent of PdG bypass was low and the
      products comprised a mixture of base pair substitutions and deletions. Sequence
      analysis of all of the products indicated that the deoxynucleoside monophosphate
      incorporated "opposite" PdG was complementary to the base 5' to PdG in the
      template strand. These findings are very similar to recent results of Efrati et
      al. (Efrati, E., Tocco, G., Eritja, R., Wilson, S. H., and Goodman, M. F. (1997)
      J. Biol. Chem. 272, 2559-2569) obtained in DNA replication of template-primers
      containing abasic sites and suggest that PdG is a non-informational lesion when
      acted upon by polymerase (pol) beta. In addition to base pair substitutions and
      one- or two-base deletions, a four-base deletion was observed and the mechanism
      of its formation was probed by site-specific mutagenesis. The results indicated
      that this deletion occurred by one-base insertion followed by slippage to form a
      four-base loop followed by extension. All of the observations on pol beta
      replication of PdG-containing template-primers are consistent with a mechanism of
      lesion bypass that involves template slippage and dNTP stabilization followed by
      deoxynucleoside monophosphate incorporation and extension. This mechanism of PdG
      bypass is completely different than that previously determined for the Klenow
      fragment of DNA polymerase I and is consistent with recent structural models for
      DNA synthesis by pol beta.

PMID- 9242699
TI  - Identification of complexes between the COOH-terminal domains of sterol
      regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating
      protein.
AB  - SREBP cleavage-activating protein (SCAP) stimulates the proteolytic cleavage of
      membrane-bound SREBPs, thereby initiating the release of NH2-terminal fragments
      from cell membranes. The liberated fragments enter the nucleus and stimulate
      transcription of genes involved in synthesis and uptake of cholesterol and fatty
      acids. Sterols repress cleavage of SREBPs, apparently by interacting with the
      membrane attachment domain of SCAP. In the present studies we show that SCAP,
      like the SREBPs, is located in membranes of the endoplasmic reticulum and nuclear
      envelope. The COOH-terminal domain of SCAP, like that of the SREBPs, is located
      on the cytosolic face of the membranes. Co-immunoprecipitation experiments show
      that SCAP and SREBP-2 form a complex that can be precipitated with antibodies to
      either component. Complex formation occurs when cells express only the COOH
      terminal domain of either SREBP-2 or SCAP, indicating that the complex forms
      between the two COOH-terminal domains. Truncation of SREBP-2 at its COOH terminus
      prevents the formation of complexes with SCAP and simultaneously reduces
      proteolytic cleavage. We conclude that proteolytic cleavage of SREBPs requires
      the formation of a complex with the COOH-terminal domain of SCAP and that SCAP is
      therefore a required element in the regulation of sterol and fatty acid
      metabolism in animal cells.

PMID- 9242700
TI  - Purification of a RNA-binding protein from rat liver. Identification as ferritin
      L chain and determination of the RNA/protein binding characteristics.
AB  - In cultured rat hepatocytes the degradation of phosphoenolpyruvate carboxykinase
      mRNA might be regulated by protein(s), which by binding to the mRNA alter its
      stability. The 3'-untranslated region of phosphoenolpyruvate carboxykinase mRNA
      as a potential target was used to select RNA-binding protein(s) from rat liver by
      the use of gel retardation assays. A cytosolic protein was isolated, which bound
      to the phosphoenolpyruvate carboxykinase mRNA 3'-untranslated region and other in
      vitro synthesized RNAs. The protein was purified to homogeneity; it had an
      apparent molecular mass of 400 kDa and consisted of identical subunits with an
      apparent size of 24.5 kDa. Sequence analysis of a tryptic peptide from the 24.5
      kDa protein revealed its identity with rat ferritin light chain. Binding of
      ferritin to RNA was abolished after phosphorylation with cAMP-dependent protein
      kinase and was augmented after dephosphorylation with alkaline phosphatase. Weak
      binding was observed in extracts from okadaic acid-treated cultured hepatocytes
      compared with untreated cells. Preincubation of ferritin with an anti
      phosphoserine or an anti-phosphothreonine antibody attenuated binding to RNA,
      while an anti-phosphotyrosine antibody generated a supershift indicating that
      phosphoserine and phosphothreonine but not phosphotyrosine residues were in close
      proximity to the RNA-binding region. Ferritin is the iron storage protein in the
      liver. Binding of ferritin to RNA was diminished in the presence of increasing
      iron concentrations, whereas the iron chelator desferal was without effect. It is
      concluded that ferritin might function as RNA-binding protein and that it may
      have important functions in the general regulation of cellular RNA metabolism.

PMID- 9242701
TI  - Ligand-independent activation domain in the N terminus of peroxisome proliferator
      activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2
      isoforms and influence of insulin.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      nuclear hormone receptor superfamily, and is an important regulator of
      adipogenesis and adipocyte gene expression. PPARgamma exists as two isoforms,
      PPARgamma1 and PPARgamma2, that differ only in their N termini. Both isoforms are
      activated by ligands that include the antidiabetic thiazoladinedione drugs and 15
      deoxy-Delta12, 14-prostaglandin J2, and potential differences in their function
      have yet to be described. We report that, in addition to a ligand-activated
      transcriptional activity, when studied under conditions of ligand depletion,
      intact PPARgamma has a ligand-independent activation domain. To identify the
      basis for this ligand-independent activation, we used GAL4-PPARgamma chimeric
      expression constructs and UAS-TK-LUC in CV1 cells and isolated rat adipocytes. In
      both cell systems, isolated PPARgamma1 and PPARgamma2 N termini have activation
      domains, and the activation function of PPARgamma2 is 5-6-fold greater than that
      of PPARgamma1. Insulin enhances the transcriptional effect mediated by both
      PPARgamma1 and PPARgamma2 N-terminal domains. These data demonstrate that 1)
      PPARgamma has an N-terminal (ligand-independent) activation domain; 2) PPARgamma1
      and PPARgamma2 N termini have distinct activation capacities; and 3) insulin can
      potentiate the activity of the N-terminal domain of PPARgamma.

PMID- 9242702
TI  - Residual cytotoxicity and granzyme K expression in granzyme A-deficient cytotoxic
      lymphocytes.
AB  - Cytotoxic lymphocytes contain granules that have the ability to induce apoptosis
      in susceptible target cells. The granule contents include perforin, a pore
      forming molecule, and several granzymes, including A and B, which are the most
      abundant serine proteases in these granules. Granzyme B-deficient cytotoxic T
      lymphocytes (CTL) have a severe defect in their ability to rapidly induce
      apoptosis in their targets, but have an intact late cytotoxicity pathway that is
      in part perforin-dependent. In this report, we have created mice that are
      deficient for granzyme A and characterized their phenotype. These mice have
      normal growth and development and normal lymphocyte development, activation, and
      proliferation. Granzyme A-deficient CTL have a small but reproducible defect in
      their ability to induce 51Cr and 125I-UdR release from susceptible allogeneic
      target cells. Since other granzyme A-like tryptases could potentially account for
      the residual cytotoxicity in granzyme A-deficient CTL, we cloned the murine
      granzyme K gene, which is linked to granzyme A in humans, and proved that it is
      also tightly linked with murine granzyme A. The murine granzyme K gene (which
      encodes a tryptase similar to granzyme A) is expressed at much lower levels than
      granzyme A in CTL and LAK cells, but its expression is unaltered in granzyme A-/-
      mice. The minimal cytotoxic defect in granzyme A-/- CTL could be due to the
      existence of an intact, functional early killing pathway (granzyme B dependent),
      or to the persistent expression of additional granzyme tryptases like granzyme K.

PMID- 9242703
TI  - Bryostatin 1 induces biphasic activation of protein kinase D in intact cells.
AB  - Bryostatin 1 and phorbol esters are both potent activators of protein kinase C
      (PKC), although their specific biological effects can differ in many systems.
      Here, we report that bryostatin 1 activates protein kinase D (PKD), a novel
      serine/threonine protein kinase, in intact Swiss 3T3 cells and secondary mouse
      embryo fibroblasts and in COS-7 cells transiently transfected with a PKD
      expression construct. The dose response of PKD activation induced by bryostatin 1
      follows a striking biphasic pattern with maximal activation achieved at a
      concentration of 10 nM. Higher concentrations of bryostatin 1 (100 nM) reduced
      PKD activation induced by phorbol 12,13-dibutyrate to levels stimulated by
      bryostatin 1 alone. Bryostatin 1-induced PKD activation was markedly attenuated
      by treatment of cells with the PKC inhibitors bisindolylmaleimide I and Ro 31
      8220. However, these agents did not inhibit PKD activity when added directly to
      in vitro kinase assays, suggesting that bryostatin 1 stimulates PKD activation
      through a PKC-dependent pathway in intact cells. Our results raise the
      possibility that activated PKD in intact cells could mediate some of the multiple
      biphasic biological responses induced by bryostatin 1.

PMID- 9242704
TI  - Modulation of interleukin (IL)-13 binding and signaling by the gammac chain of
      the IL-2 receptor.
AB  - Interleukin (IL)-13 and IL-4 are cytokine products of TH2 cells which exert
      similar effects in a variety of cell types. We recently described IL-13R
      expression on human renal cell and colon carcinoma cells and demonstrated that
      gammac is not a component of IL-13R or IL-4R systems in these cells. In lymphoid
      cells such as B cells and monocytes, which respond to IL-13, gammac is a
      component of IL-4R but does not appear to be a component of IL-13R. Furthermore,
      while significant IL-13 binding is observed on carcinoma cells, IL-13 barely
      binds these lymphoid cells and the binding characteristics are different. To
      better understand the role of gammac in IL-13 binding and signaling, we have
      transfected a renal cell carcinoma cell line with gammac and examined IL-13 and
      IL-4 binding and signaling. IL-13 binding as well as IL-13 and IL-4 signaling
      through the JAK-STAT signaling pathway were severely inhibited. This inhibition
      was paralleled by a loss of expression of one of the IL-13R chains and
      intercellular cell adhesion molecule-1. Thus, although gammac has been shown to
      enhance IL-4 binding and function in some cell types, its influence on IL-13R
      function in tumor cells appear to be largely negative.

PMID- 9242705
TI  - A specific role for the phosphorylation of mammalian acidic ribosomal protein P2.
AB  - The acidic ribosomal proteins P1-P2 from rat liver were overproduced for the
      first time by expression of their cDNA in Escherichia coli. They were tested for
      their ability to reactivate inactive P1-P2-deficient core particles derived from
      60 S ribosomal subunits treated with dimethylmaleic anhydride, in poly(U)
      directed poly(Phe) synthesis. The recombinant P1-P2 were unable to reactivate
      these core particles although they could bind to them. When recombinant P1-P2 had
      been phosphorylated first with casein kinase II, they were as efficient in the
      reactivation process as P1-P2 extracted with ethanol/KCl from the 60 S subunits.
      Reconstitution experiments were carried out using all possible combinations of
      the two recombinant proteins phosphorylated or not. Reactivation of the core
      particles required the presence of both P1 and P2 with the latter in its
      phosphorylated form. These experiments reveal a distinct role for P1 and P2 in
      protein synthesis. Phosphorylated P2 produced a partial quenching of the
      intrinsic fluorescence of eukaryotic elongation factor 2, which was not observed
      with the unphosphorylated protein. This result demonstrates the existence of an
      interaction between phosphorylated P2 and eukaryotic elongation factor 2. P2 also
      quenched part of the intrinsic fluorescence of P1, due to the interaction between
      the two proteins.

PMID- 9242706
TI  - Projection map of cytochrome b6 f complex at 8 A resolution.
AB  - The structure of the cytochrome b6 f complex has been investigated by electron
      microscopy and image analysis of thin three-dimensional crystals. Electron
      micrographs of negatively stained specimens were recorded and showed optical
      diffraction peaks to 10 A resolution. A projection map was calculated at 8 A
      resolution and showed the presence of cytochrome b6 f dimers. The extramembrane
      part of each monomer featured a C shape, with mean external diameter
      approximately of 53 A and an internal groove approximately 14 A long and
      approximately 9 A wide. Within each monomer, strong features were clearly
      resolved and tentatively attributed to some of the subunits of the cytochrome b6
      f complex. The data are consistent with the Rieske iron-sulfur protein lying
      close to the monomer-monomer interface and the heme-bearing domain of cytochrome
      f far from it.

PMID- 9242707
TI  - Utilization of a recombinant substrate rAgg1 to study the biochemical properties
      of aggrecanase in cell culture systems.
AB  - This paper describes the first report of the production and use of an artificial
      recombinant protein substrate to study "aggrecanase" activity. The substrate
      (rAgg1) is composed of the complete interglobular domain (IGD) of human aggrecan
      flanked by the "marker" sequences FLAGTM at the amino terminus and the human
      immunoglobulin G1 constant region at the carboxyl terminus. The expressed protein
      occurs as large multimolecular aggregates (>120 kDa) that, upon reduction,
      consist of a major isoform of 72 kDa (containing the IGD) and a minor 39-kDa
      species that through alternative splicing has had the IGD deleted. Using this
      recombinant substrate we developed a novel agarose cell culture system containing
      either rat chondrosarcoma or bovine chondrocytes that could be used in studies of
      the biochemical characterization of aggrecanase activities. These studies showed
      the following. (i) rAgg1 is a suitable substrate for aggrecanase proteolysis.
      (ii) Aggrecanase activity was specifically induced by exposing chondrocytes to
      retinoic acid. (iii) A considerable time period was required to synthesize and/or
      activate aggrecanase, with considerable differences in that found in rat
      chondrosarcoma versus bovine chondrocyte culture systems. (iv) Aggrecanase
      cleavage of the aggrecan IGD does not require the presence of the G1 or G2
      globular domains or keratan sulfate post-translational modification in the IGD.
      (v) Aggrecanase is a diffusible activity that does not require association with
      the chondrocyte plasma membrane or immediate pericellular matrix for its action.

PMID- 9242708
TI  - Purification and characterization of novel heparin-binding growth factors in
      uterine secretory fluids. Identification as heparin-regulated Mr 10,000 forms of
      connective tissue growth factor.
AB  - Uterine growth factors are potential effector molecules in embryo growth
      signaling pathways. Pig uterine luminal flushings contained a heparin-binding
      growth factor (HBGF) that required 0.8 M NaCl for elution from heparin columns
      and was termed HBGF-0.8. This factor, which was heat- and acid-labile and of Mr
      10,000 as assessed by gel filtration, stimulated DNA synthesis in fibroblasts and
      smooth muscle cells but not endothelial cells. Two forms of HBGF-0.8, termed HBGF
      0.8-P1 and HBGF-0.8-P2, exhibited differential heparin-binding properties. SDS
      polyacrylamide gel electrophoresis showed that each form of HBGF-0.8 migrated
      with an apparent Mr of 10, 000 under reducing conditions. Amino acid sequencing
      revealed the N-terminal sequence EENIKKGKKXIRTPKI for HBGF-0.8-P1 and
      ENIKKGKKXIRT for HBGF-0.8-P2. These sequences corresponded, respectively, to
      residues 247-262 and 248-259 of the 349-residue predicted primary translation
      product of porcine connective tissue growth factor (pCTGF). 10-kDa CTGF-mediated
      fibroblast DNA synthesis was modulated by exogenous heparin, and CTGF
      immunoreactive proteins of 10, 16, and 20 kDa were present in unfractionated
      uterine luminal flushings. These data reveal the identity of a novel growth
      factor in uterine fluids as a highly truncated form of CTGF and show that the N
      terminal two-thirds of the CTGF primary translation product is not required for
      mitogenic activity or heparin binding.

PMID- 9242709
TI  - Transcriptional down-regulation of the metastasis-inducing S100A4 (p9Ka) in
      benign but not in malignant rat mammary epithelial cells by GC-factor.
AB  - The S100-related calcium-binding protein S100A4 (p9Ka) is expressed at a low
      level in rat mammary epithelial cells from normal mammary gland and benign
      mammary tumors. In transgenic mice, expressed rat S100A4 transgenes co-operate
      with the activated c-erbB-2 oncogene, neu, to form metastatic mammary tumors.
      Elevated levels of S100A4 (p9Ka) in cultured benign rat or mouse mammary
      epithelial cells are associated with the induction of metastatic capability. A
      cis-acting sequence related to the consensus recognition sequence of GC-factor,
      1,300 base pairs upstream of the start site of transcription of the rat S100A4
      gene, acts as a cis-acting inhibitor of transcription of the S100A4 (p9Ka) gene
      in a low S100A4 (p9Ka)-expressing benign rat mammary epithelial cell line, but
      not in highly expressing rat mammary epithelial cell lines. There is an inverse
      relationship between the level of S100A4 (p9Ka) mRNA and the level of GC-factor
      mRNA in a range of rat mammary cell lines. The results suggest a novel mechanism
      for regulating the expression of the mRNA encoding an S100 protein.

PMID- 9242710
TI  - Phosphorylation and calmodulin binding of the metabotropic glutamate receptor
      subtype 5 (mGluR5) are antagonistic in vitro.
AB  - Metabotropic glutamate receptors, which are members of a G protein-coupled
      receptor family, mediate the glutamate responses by coupling to the intracellular
      signal transduction pathway. We herein report that calmodulin (CaM) interacts
      with the metabotropic glutamate receptor subtype 5 (mGluR5) in a Ca2+-dependent
      manner in vitro. CaM is capable of binding on two distinct sites in the COOH
      terminal intracellular region of the receptor with different affinities. The CaM
      binding domains are separated by an alternatively spliced exon cassette present
      in one of the splicing isoforms of mGluR5. By using fusion proteins and synthetic
      peptides we showed that protein kinase C phosphorylates both CaM binding regions.
      This phosphorylation is inhibited by the binding of CaM to the receptor, and
      conversely the binding is inhibited by the phosphorylation. These antagonisms of
      the CaM binding and phosphorylation thus suggest the possibility that they
      regulate the receptor responses in vivo.

PMID- 9242711
TI  - Human lysophosphatidic acid acyltransferase. cDNA cloning, expression, and
      localization to chromosome 9q34.3.
AB  - Lysophosphatidic acid (1-acyl-sn-glycero-3-phosphate (LPA)) is a phospholipid
      with diverse biological activities. The mediator serves as an intermediate in
      membrane phospholipid metabolism but is also produced in acute settings by
      activated platelets. LPA is converted to phosphatidic acid, itself a lipid
      mediator, by an LPA acyltransferase (LPAAT). A human expressed sequence tag was
      identified by homology with a coconut LPAAT and used to isolate a full-length
      human cDNA from a heart muscle library. The predicted amino acid sequence bears
      33% identity with a Caenorhabditis elegans LPAAT homologue and 23-28% identity
      with plant and prokaryotic LPAATs. Recombinant protein produced in COS 7 cells
      exhibited LPAAT activity with a preference for LPA as the acceptor
      phosphoglycerol and arachidonyl coenzyme A as the acyl donor. Northern blotting
      demonstrated that the mRNA is expressed in most human tissues including a panel
      of brain subregions; expression is highest in liver and pancreas and lowest in
      placenta. The human LPAAT gene is contained on six exons that map to chromosome
      9, region q34.3.

PMID- 9242712
TI  - Interleukin-1-induced ether-linked diglycerides inhibit calcium-insensitive
      protein kinase C isotypes. Implications for growth senescence.
AB  - It is hypothesized that inflammatory cytokines and vasoactive peptides stimulate
      distinct species of diglycerides that differentially regulate protein kinase C
      isotypes. In published data, we demonstrated that interleukin-1, in contrast to
      endothelin, selectively generates ether-linked diglyceride species (alkyl, acyl-
      and alkenyl, acylglycerols) in rat mesangial cells, a smooth muscle-like pericyte
      in the glomerulus. We now demonstrate both in intact cell and in cell-free
      preparations that these interleukin-1 receptor-generated ether-linked
      diglycerides inhibit immunoprecipitated protein kinase C delta and epsilon but
      not zeta activity. Neither interleukin-1 nor endothelin affect de novo protein
      expression of these protein kinase C isotypes. As down-regulation of calcium
      insensitive protein kinase C isotypes has been linked to antimitogenic activity,
      we investigated growth arrest as a functional correlate for IL-1-generated ether
      linked diglycerides. Cell-permeable ether-linked diglycerides mimic the effects
      of interleukin-1 to induce a growth-arrested state in both G-protein-linked
      receptor- and tyrosine kinase receptor-stimulated mesangial cells. This signaling
      mechanism implicates cytokine receptor-induced ether-linked diglycerides as
      second messengers that inhibit the bioactivity of calcium-insensitive protein
      kinase C isotypes resulting in growth arrest.

PMID- 9242713
TI  - Tyrosine kinase inhibition reduces i(f) in rabbit sinoatrial node myocytes.
AB  - We studied pacemaker current (i(f)), the inward current activated by
      hyperpolarization in rabbit sinoatrial (SA) node myocytes, with the permeabilized
      patch-clamp technique. The tyrosine kinase inhibitors genistein (50 microM) or
      herbimycin A (35 microM) reduced the amplitude of i(f) in response to step
      hyperpolarizations in the diastolic range of potentials. A two-step voltage-clamp
      protocol revealed that the reduction in i(f) is due to a decrease in maximal i(f)
      conductance. The observed effects are due to tyrosine kinase inhibition since an
      inactive analog of genistein did not reduce i(f). To further examine the
      mechanism of action, we added 2 mM chlorophenylthio cAMP (CPTcAMP, a membrane
      permeant cAMP analog) to the bathing Tyrode, which increased i(f). Genistein
      still reduced i(f) in the presence of CPTcAMP. This suggests that the pathway
      mediating the actions of tyrosine kinase inhibition on i(f) is independent of
      cAMP- or protein-kinase-A-mediated phosphorylation.

PMID- 9242714
TI  - Multisite regulation of insulin secretion by cAMP-increasing agonists: evidence
      that glucagon-like peptide 1 and glucagon act via distinct receptors.
AB  - The mechanisms by which glucagon-like peptide 1(7-36)amide (GLP-1[7-36]amide)
      potentiates insulin secretion were investigated by measurements of whole-cell K+
      and Ca2+ currents, membrane potential, the cytoplasmic Ca2+ concentration
      ([Ca2+]i) and exocytosis in mouse pancreatic B-cells. GLP-1(7-36)amide (10 nM)
      stimulated glucose-induced (10 mM) electrical activity in intact pancreatic
      islets. The effect was manifested as a 34% increase in the duration of the bursts
      of action potentials and a corresponding 28% shortening of the silent intervals.
      GLP-1(7-36)amide had no effect on the electrical activity at subthreshold glucose
      concentrations (< or = 6.5 mM). In cultured B-cells, GLP-1(7-36)amide produced a
      decrease of the whole-cell ATP-sensitive K+ (KATP) conductance remaining at 5 mM
      glucose by approximately 30%. This effect was associated with membrane
      depolarization and the initiation of electrical activity. GLP-1(7-36)amide
      produced a protein-kinase-A-(PKA-) and glucose-dependent fourfold potentiation of
      Ca(2+)-induced exocytosis whilst only increasing the Ca2+ current marginally. The
      stimulatory action of GLP-1(7-36)amide on exocytosis was mimicked by the
      pancreatic hormone glucagon and exendin-4, a GLP-1 receptor agonist. Whereas the
      stimulatory action of GLP-1(7-36)amide could be antagonized by exendin-(9-39),
      this peptide did not interfere with the ability of glucagon to stimulate
      exocytosis. We suggest that GLP-1(7-36)amide and glucagon stimulate insulin
      secretion by binding to distinct receptors. The GLP-1(7-36)amide-induced
      stimulation of electrical activity and Ca2+ influx can account for (maximally) a
      doubling of insulin secretion. The remainder of its stimulatory action results
      from a cAMP/PKA-dependent potentiation of Ca(2+)-dependent exocytosis exerted at
      a stage distal to the elevation of [Ca2+]i.

PMID- 9242715
TI  - Fever and production of cytokines in response to repeated injections of muramyl
      dipeptide in guinea-pigs.
AB  - Fever and systemic plasma levels of the cytokines tumour necrosis factor alpha
      (TNF) and interleukin-6 (IL-6) were measured in guinea-pigs in response to single
      or repeated intramuscular injections of 100 micrograms/kg muramyl-dipeptide
      (MDP). In a pilot study (experiment 1), MDP-induced fever was monitored for 8 h.
      The first fever phase 90-360 min after injection of MDP was followed by the
      second phase which continued beyond the duration of this experiment. High
      circulating levels of TNF and IL-6 were detected just before body core
      temperature started to rise. Within the next 90 min TNF declined again by more
      than 90% while IL-6 remained elevated. In experiment 2, the effects of repeated
      injections of MDP (5 times at intervals of 3 days) on the same parameters were
      investigated. In this paradigm, the febrile response started earlier (60 min
      after injection) and the first phase of fever remained manifest until 360 min
      after injection, while the late phase, measured 360-720 min after injection, was
      attenuated. Circulating, bioactive TNF and IL-6, measured 60 and 180 min after
      MDP was administered, were the same in response to the first, third, and fifth
      injection. In experiment 3, the influence of five repeated MDP injections on the
      abdominal temperature was measured for 22 h, and circulating cytokines were
      analysed before (360 min after injection) and during (480 min after injection)
      the late phase of MDP-induced fever. The late phase of MDP-induced fever 7-22 h
      after injection was attenuated in response to the second and further
      administrations of this pyrogen. At 6 h after the first, third, and fifth
      administration of MDP, only traces of TNF alpha were measured, 2 h later no
      bioactive TNF was detected at all. At these times also IL-6 declined again,
      compared with the activity of this cytokine measured during the early phase of
      MDP fever, but was still present in elevated amounts. Compared with the values
      measured in response to the third and fifth injections of MDP, circulating IL-6
      was higher 360 min and 480 min after the first injection. It remains speculative
      whether the longer duration of elevated IL-6 in plasma is related to the
      development of the long-lasting, late phase of MDP-induced fever, which was only
      observed after the first of five repeated injections of MDP at intervals of 3
      days.

PMID- 9242716
TI  - Exogenous caldesmon promotes relaxation of guinea-pig skinned taenia coli smooth
      muscles: inhibition of cooperative reattachment of latch bridges?
AB  - In smooth muscle, the state of prolonged contraction (latch state) is associated
      with very slow energy turnover and cycling of crossbridges that are
      dephosphorylated. A similar state may be reproduced in skinned fibres when the
      calcium-induced contraction is terminated by calcium removal with
      ethylenebis(oxonitrilo)tetraacetate (EGTA) and, during the slow relaxation that
      follows, force is maintained by dephosphorylated crossbridges that cycle slowly
      or not at all and may cooperatively reattach after detachment (Khromov et al.
      1995, Biophys J 69:2611-2622). In guinea-pig skinned taenia coli that has been
      pretreated by prolonged incubation with caldesmon (5 microM), the rate of
      relaxation is approximately 1.6 times greater than in untreated controls, with
      half-times of relaxation being 1.3 and 2.1 min, respectively. In contrast,
      preloading the fibres with calponin does not accelerate relaxation. Preloading
      the fibres with caldesmon also accelerates the relaxation of skinned fibres from
      the state of rigor contraction when the latter is terminated by immersion into an
      ATP-containing relaxing solution or, in the presence of inorganic phosphate (Pi),
      also by flash-photolytic release of ATP from caged-ATP. Even in the latter case,
      relaxation is comparatively slow, possibly because of cooperative reattachment of
      dephosphorylated crossbridges which delays net crossbridge detachment and hence
      relaxation. We propose that by inhibition of cooperative reattachment caldesmon
      accelerates relaxation, even in the presence of Pi, and that the latch-like state
      of skinned fibres is supported by dephosphorylated cooperatively attaching
      crossbridges and may be regulated by the activity of caldesmon in the smooth
      muscle cell.

PMID- 9242717
TI  - Effect of cAMP and ATP on the hyperpolarization-activated current in mouse dorsal
      root ganglion neurons.
AB  - In mouse dorsal root ganglion (DRG) neurons the activation curve of the
      hyperpolarization-activated current (Ih) shifted towards depolarized potentials
      when cAMP was present in the pipette. The relation between the midpoint potential
      and cAMP concentration could be described by a Hill function with a half-maximal
      concentration of 0.55 microM cAMP, reflecting a direct action of cAMP on the
      channel. With 5 mM ATP and a saturating concentration of cAMP an additional shift
      of the midpoint potential is observed which can be explained by phosphorylation.
      Application of Rp-cAMPS and Sp-cAMPS support the hypothesis of both a
      phosphorylation pathway and a direct effect exhibited by these molecules. The
      bell-shaped curves, relating the time constants for the slow and fast current
      components to the voltage, shifted towards positive membrane potentials when cAMP
      and ATP were in the pipette. The fully activated Ih/voltage relation and the
      reversal potential were not dependent on the presence of cAMP or ATP in the
      pipette. The mean resting membrane potential of -59 mV, using the perforated
      patch configuration, hyperpolarized in the presence of extracellular CsCl. In the
      whole-cell configuration the resting membrane potential was significantly more
      negative at 0 microM cAMP (-61 mV) than at 100 microM cAMP (-57 mV). Thus, the
      activation of Ih, regulated by both the intracellular cAMP and the ATP
      concentration, may influence the excitability of DRG neurons.

PMID- 9242718
TI  - Mechanical properties and myosin heavy chain isoform composition of skinned
      skeletal muscle fibres from a human biopsy sample.
AB  - Experiments were conducted to investigate the mechanics of contraction of
      chemically skinned muscle fibre segments of a biopsied sample of single human
      quadriceps muscle. Subsequently, the isoforms of the myosin heavy chain (MHC)
      were analysed by sodium dodecyl sulphate (SDS) gel electrophoresis. Of the 41
      fibres, 26 contained MHCI (type I), 11 of the fibres contained MHCIIa (type IIA),
      and 4 of the fibres contained both MHCI and MHCIIa (of which MHCIIa was always
      slightly predominant (type IIC)). Distinct differences between fibre types were
      found in terms of the kinetics of force responses following stepwise length
      changes (order of velocity: IIA > IIC > I). The differences in maximal shortening
      velocity and in the kinetics of Ca(2+)-dependent activation were of the same
      order, but much less pronounced. Type I fibres had significantly greater fibre
      diameters than type IIA fibres. No significant differences were found among
      different fibre types in terms of isometric tension, resting sarcomere length or
      the length change needed to discharge the elasticity of maximally Ca(2+)
      activated fibres (V0 value). The distribution of shortening velocity and kinetics
      of stretch activation values suggest that two muscle fibre subtypes may exist in
      human type I fibres.

PMID- 9242719
TI  - Hyperpolarizing current of the Na/K ATPase contributes to the membrane
      polarization of the Purkinje cell in rat cerebellum.
AB  - The contribution of the Na/K ATPase (pump) current to the polarization of the
      Purkinje cell has been studied using slices of the rat cerebellum by blocking the
      pump with dihydro-ouabain (DHO) while recording the membrane potential with
      microelectrodes in the somata. From our recordings, it appeared that blocking the
      pump depolarized the Purkinje cells more rapidly than might be expected from
      shifts in Na+ and K+ concentrations, suggesting the removal of a hyperpolarizing
      current. Application of DHO, in the presence of tetrodotoxin (TTX), led to
      calcium spike firing and plateau-like discharges suggesting activation of voltage
      dependent calcium channels in the dendrites. Adding 2 mM CO2+ to the medium did
      not prevent the depolarizations. Removing calcium from the bathing medium
      containing 2 mM CO2+ blocked the spiking activity but DHO application still
      produced a depolarization. Experiments to measure the current inhibited by DHO
      indicated that the Na/K pump supplies a constant current of 240 pA. Substitution
      of the sodium with choline produced a hyperpolarization, during which DHO had no
      effect on the membrane potential. Substitution of the sodium with lithium
      produced only a slowly developing depolarization. It is concluded that in the
      cerebellar Purkinje cell, a continuous sodium ion influx activates the pumps
      which produce a current that directly contributes to the membrane polarization.
      Possible pathways for this sodium influx are discussed.

PMID- 9242720
TI  - In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early
      gene expression.
AB  - This study aimed to examine the influence of acute tissue hypoxygenation on the
      expression of immediate early genes in different rat tissues. To this end male
      Sprague-Dawley rats were exposed to 0.1% carbon monoxide for 0.5, 1 and 6 h or to
      9% oxygen for 6 h and mRNA levels for c-jun, c-fos, c-myc and EGR-1 were assayed
      by RNase protection in hearts, kidneys, livers and lungs. We found that hypoxia
      increased c-jun mRNA levels between twofold (lung) and eightfold (liver) in all
      organs examined; c-fos mRNA increased between three-fold (lung) and 20-fold
      (heart); c-myc mRNA increased between twofold (lung) and sixfold (heart); and EGR
      1 mRNA increased between twofold (lung) and sixfold (heart). Our findings suggest
      that acute tissue hypoxygenation is a general stimulus of the expression of
      immediate early genes in vivo. With regard to the sensitivity to hypoxia, organ
      differences appear to exist in that the lung is rather insensitive, whilst the
      heart is rather sensitive.

PMID- 9242721
TI  - The intrinsic Cl- conductance of mouse kidney cortex brush-border membrane
      vesicles is not related to CFTR.
AB  - Brush-border membrane vesicles (BBMV) were prepared from whole Balb/c mice
      kidneys by a Mg2+ precipitation technique. The presence of an intrinsic Cl-
      conductance co-expressed with Na+/glucose cotransport was inferred by the anion
      dependence of [14C]glucose uptake and overshoot with inward Na(+)-anion
      gradients. In Na(+)-equilibrated conditions, an inside-negative membrane
      potential difference (p.d.) produced by an inward Cl- gradient alone was capable
      of driving intravesicular [14C]glucose accumulation. The apparent anion
      conductance had a selectivity of Br- = I- = Cl- > F- > > gluconate, was inhibited
      by 0.5 mM 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) but was unaffected
      by 0.5 mM 4,4'-diisothiocyanatostilbene 2,2'-disulphonate (DIDS). BBMV were
      isolated from mice in which the CFTR gene had been disrupted by a termination
      mutation (-/-) and compared with normal litter mates (+/+) and heterozygotes (
      /+)[18]. [14C]Glucose uptake in NaCl media was significantly greater than glucose
      uptake in Na gluconate media for all three genotypes measured at 20 s: for
      homozygous -/- animals [14C]glucose uptake was increased by 2.80 +/- 0.53 fold in
      Cl- media compared to gluconate media, n = 6; for wild-type +/+, by 2.16 +/- 0.53
      fold, n = 8; and for heterozygous +/- animals, by 2.17 +/- 0.45 fold, n = 8. The
      observation of a Cl-(-)dependent component in BBMV isolated from homozygous -/-
      mutant animals shows that the chloride conductance in these vesicles cannot be
      due to CFTR expression.

PMID- 9242722
TI  - Effects of nicotine on human nasal epithelium: evidence for nicotinic receptors
      in non-excitable cells.
AB  - We investigated the effects of nicotine and its derivate nicotine di-d-tartrate
      on primary cultured human nasal epithelial cells. Both substances evoked an
      increase in the intracellular free calcium concentration. In the presence of
      extracellular Ca2+ the cytosolic Ca2+ ([Ca2+]i) increase was long lasting,
      whereas in the absence of external Ca2+ there was a transient increase of [Ca2+]i
      indicating that nicotine has an influence on Ca2+ conductances across the
      membranes and on intracellular Ca2+ stores. Both effects could be blocked by the
      nicotinic receptor antagonist methyllycaconitine (MLA). Apical or basolateral
      application of nicotine during transepithelial transport measurements with
      confluent monolayers of cultured human nasal cells resulted in a significant,
      reversible decrease of amiloride-sensitive sodium absorption with an apparent
      half-maximal blocker concentration of about 950 microM. To exclude the
      possibility that remnant neuronal components were responsible for the observed
      effects we used tetrodotoxin and verapamil to block putative neuronal channels
      and 4-(4-diethylamino)styryl-N-methylpyridinium iodide (4-di-2-Asp) to stain
      neuronal tissue. Both experimental approaches demonstrated that there were no
      neuronal-mediated effects. These results indicate the direct effects of nicotine
      on human nasal epithelium, giving the first evidence of the existence of
      nicotinic receptors in non-excitable cells.

PMID- 9242723
TI  - Possible contribution of impaired sodium excretion to the development and
      maintenance of hypertension: a study of the isolated kidneys of the Prague
      hypertensive rat.
AB  - We have shown previously that in the Prague Hypertensive Rat (PHR) "hypertension
      travels with the kidney" and that the kidney appears to produce an as yet unknown
      "hypertensogenic" substance. Since enhanced sodium retention could also
      contribute to this type of hypertension, this possibility was tested in isolated
      perfused kidneys from PHR and from its normotensive substrain, PNR, bred from the
      same parent pair as PHR, at two levels of perfusion pressure (PP), i.e 110 and
      150 mmHg (where 1 mmHg = 133.3 Pa). Young (6-week-old) and adult (12-week-old)
      animals of both substrains were used. In young PHR and PNR, there was no
      significant difference in haemodynamic parameters when the kidneys were perfused
      at either low or high PP. Surprisingly, water and sodium excretion rates were
      also the same at both PP values in both substrains, which thus--at this age--do
      not exhibit the well known "pressure diuresis and natriuresis". In adult PNR,
      perfusate flow and glomerular filtration rates (GFR) were independent of the
      level of PP (autoregulation) whereas water and sodium excretion rates were
      significantly higher at 150 than at 110 mmHg, a finding similar to those found in
      vivo studies (pressure diuresis and natriuresis). In adult PHR, however, both
      perfusate flow rate and GFR were pressure dependent: only at the high PP were
      values of both GFR and perfusate flow obtained which were similar to those in the
      PNR at low pressure. Sodium excretion was lower, and its tubular reabsorption
      higher, in PHR than in PNR at both levels of perfusion. Again, in PHR, the higher
      PP was needed to achieve the same rate of sodium excretion as in PNR at the lower
      pressure. Thus, the kidneys of PHR retain sodium at a given PP compared with the
      kidneys from PNR. This may contribute to the development and/or maintenance of
      hypertension in the PHR.

PMID- 9242724
TI  - Two types of omega-agatoxin IVA-sensitive Ca2+ channels are coupled to adrenaline
      and noradrenaline release in bovine adrenal chromaffin cells.
AB  - To clarify the role of P-type Ca2+ channels in catecholamine release from adrenal
      chromaffin cells we examined the concentration dependence of the effect of omega
      agatoxin IVA on the release both of adrenaline and noradrenaline induced by a
      K(+)-evoked depolarization. omega-Agatoxin IVA caused a biphasic dose-dependent
      inhibition of secretion with a high-potency component (IC50 < 1 nM), responsible
      for 10-15% of catecholamine release evoked by 70 mM K+, and a low-potency
      component that accounted for about 40% of release, with IC50 values of 57 nM and
      48 nM for noradrenaline and adrenaline release, respectively. The release of
      catecholamines from chromaffin cells was also inhibited dose dependently by omega
      conotoxin MVIIC with IC50 values of 182 and 218 nM for noradrenaline and
      adrenaline release, respectively. The effects of 3 nM omega-agatoxin IVA and 3
      microM omega-conotoxin MVIIC were additive, indicating that at the concentrations
      used the toxins were acting at independent sites, presumably, P- and Q-type Ca2+
      channels. The blockade of Q-type channels inhibited the release of adrenaline (72
      +/- 4.1%) significantly more than the release of noradrenaline (50 +/- 2.7%),
      suggesting a higher density or a closer coupling of these channels to exocytosis
      in adrenergic chromaffin cells. The blockade of P-type channels caused a greater
      inhibition of catecholamine secretion at low levels of K(+)-evoked depolarization
      and shorter times of stimulation than that observed at higher levels of
      stimulation. The contribution of Q-type channels to catecholamine secretion did
      not change significantly with the intensity of stimulation. The data show that
      two types of omega-agatoxin IVA-sensitive Ca2+ channels are coupled to
      catecholamine release in chromaffin cells, and that the contribution of P-type
      channels to secretion is larger at low levels of depolarization.

PMID- 9242725
TI  - Absence of evidence for a powerful tonic baroreflex-mediated inhibition on
      catechol activity in the rat rostral ventrolateral medulla: in vivo voltammetric
      evidence during sino-aortic deafferentation.
AB  - To test in a catechol-specific and dynamic manner for the existence of a powerful
      long-lasting inhibition arising from barosensitive afferents that depresses the
      activity of adrenergic neurons in the rostral ventrolateral medulla (RVLM), in
      vivo voltammetry was used before and after acute sino-aortic deafferentation.
      Rats were anaesthetized with pentobarbital or halothane and ventilated with a
      mixture of air and oxygen. Snares were inserted around the vagus, the
      glossopharyngeal and the superior laryngeal nerves. After placing the animal
      prone in the stereotaxic frame and stabilization at a high mean arterial pressure
      (MAP approximately 120 mmHg), the snares were rapidly closed to produce complete
      barodeafferentation, assessed by loss of heart rate responses and changes in
      renal nerve sympathetic activity in response to vasoactive agents. Recording of a
      catechol signal was maintained in the RVLM during deafferentation. Under
      pentobarbital-induced anaesthesia (n = 5), deafferentation did not lead to a
      significant change in the catechol signal within the deafferented group. Under
      halothane-induced anaesthesia and phenylephrine-induced high baseline pressure (n
      = 5), no changes in the catechol signal were observed upon deafferentation (not
      significant vs. sham animals: n = 5). This failure to demonstrate a major
      increase in catechol activity upon deafferentation does not fit with the
      hypothesis that a powerful tonic baroreflex-mediated inhibition depresses the
      activity of adrenergic RVLM barosensitive bulbospinal neurons, even when the
      baseline MAP is high. Rather, these data are compatible with weak or no
      inhibition of catechol activity by the baroreceptors and a nonessential role of
      adrenergic neurons within the baroreceptor reflex arc itself: the adrenergic
      neurons may not be in series within this arc but in parallel with the arc. This
      interpretation is in keeping with newer schemas of autonomic core circuitry that
      are devoid of adrenergic neurons.

PMID- 9242726
TI  - Intracellular pH and calcium signalling in rat pancreatic acinar cells.
AB  - Intracellular free Ca2+ signals, which occur in many secretory cell types after
      the binding of some secretagogues to their membrane receptors, are due to Ca2+
      mobilization from internal stores and Ca2+ influx from the extracellular space.
      There is also growing evidence for a modulatory role of intracellular pH in Ca2+
      metabolism. In fact it has been proposed that Ca2+ stores in pancreatic acinar
      cells may be loaded by Ca2+/H+ exchange. The aim of this paper was to establish
      the effect of intracellular pH on Ca2+ signalling in pancreatic acinar cells.
      Application of the proton carrier nigericin impairs Ca2+ mobilization in response
      to cholecystokinin (CCK-8), and application of membrane-permeant bases or acids
      inhibits CCK-8-evoked intracellular Ca2+ oscillations. Both nigericin and a cell
      permeant weak base release Ca2+ from internal stores. However, cytosolic
      acidification by removal of extracellular Na+ had no effect on the resting or
      stimulated cytosolic Ca2+ concentration. After depletion of Ca2+ stores by a
      maximal concentration of CCK-8, nigericin and ionomycin released a residual Ca2+
      pool. Taken together, our results show that in pancreatic acinar cells Ca2+
      signals require the existence of subcellular gradients of pH and indicate the
      presence of acidic pools of Ca2+.

PMID- 9242727
TI  - Kinetic properties of DM-nitrophen and calcium indicators: rapid transient
      response to flash photolysis.
AB  - We describe a high temporal resolution confocal spot microfluorimetry setup which
      makes possible the detection of fluorescence transients elicited by Ca2+
      indicators in response to large (50-200 microM), short duration (< 100 ns), free
      [Ca2+] transients generated by laser flash photolysis of DM-nitrophen (DM-n;
      caged Ca2+). The equilibrium and kinetic properties of the commercially available
      indicators Fluo-3, Rhod-2, CalciumOrange-5N (COr-5N) and CalciumGreen-2 (CGr-2)
      were determined experimentally. The data reveal that COr-5N displays simple, fast
      response kinetics while, in contrast, Fluo-3, Rhod-2 and CGr-2 are characterized
      by significantly slower kinetic properties. These latter indicators may be
      unsuitable for tracking Ca2+ signaling events lasting only a few milliseconds. A
      model which accurately predicts the time course of fluorescence transients in
      response to rapid free [Ca2+] changes was developed. Experimental data and model
      predictions concur only when the association rate constant of DM-n is
      approximately 20 times faster than previously reported. This work establishes a
      quantitative theoretical framework for the study of fast Ca2+ signaling events
      and the use of flash photolysis in cells and model systems.

PMID- 9242729
TI  - Pulse oximetry: a new way of determining the heart rate in chicken embryos.
AB  - With pulse oximetry it is possible to record the pulse-synchronic variation of
      the oxygen saturation due to variable blood flow during systole and diastole. In
      the present study on chicken embryos, the pulse rate based on oximetry was
      compared with the heart rate recorded by means of ECG. We conclude that the pulse
      curve detected by means of pulse oximetry can be used to determine the heart rate
      in chicken embryos between day 12 and day 20 of incubation.

PMID- 9242728
TI  - Use of a bicistronic GFP-expression vector to characterise ion channels after
      transfection in mammalian cells.
AB  - Transient transfection of ion channels into mammalian cells is a useful method
      with which to study ion channel properties. However, a general problem in
      transient transfection procedures is how to select cells that express the
      transfected cDNA. We have constructed a bicistronic vector, pCINeo/IRES-GFP,
      which utilises a red-shifted variant of Green Fluorescent Protein as an in vivo
      cell marker. Incorporation of an ion channel cDNA into the bicistronic unit
      allows coupled expression of the ion channel and Green Fluorescent Protein. After
      transient transfection of COS cells with pCINeo/IRES-GFP containing a rat delayed
      rectifier K+ channel cDNA (RCK1, Kv1.1), all green cells (n = 32) expressed the
      RCK1 channel as identified by the well known kinetics, K+ selectivity and
      pharmacology of Kv1.1. In contrast, non-fluorescent cells (n = 24) were negative
      with respect to RCK1 expression. It is concluded that the bicistronic pCINeo/IRES
      GFP vector provides an efficient and non-invasive way of identifying cells which
      express ion channels after transfection. This novel method should greatly
      facilitate functional studies of ion channels transfected into mammalian cells.

PMID- 9242730
TI  - Nicotine inhibits slowly inactivating K+ currents in rat cultured striatal
      neurons.
AB  - As shown on cultured striatal neurons recorded in whole-cell configuration, both
      acetylcholine (in the presence of atropine) and nicotine reduced voltage
      dependent outward currents. Although, at early postnatal ages, outward currents
      in these cells are mainly carried by rapidly and slowly inactivating K+ channels,
      these inhibitions resulted from a selective and reversible effect on the slowly
      inactivating K+ conductance (IK+). This action was blocked by the nicotinic
      antagonist dihydro-beta-erythroidine and reproduced by nicotinic agonists. When
      neurons were recorded under current-clamp conditions, nicotine increased
      reversibly their firing rate generated by step depolarizations. Therefore, in
      addition to its well documented muscarinic effects, acetylcholine also controls
      K+ currents in striatal neurons through mechanisms mediated by nicotinic
      receptors.

PMID- 9242731
TI  - "To be, or not to be: that is the question...".

PMID- 9242732
TI  - The employment market for 1996 diagnostic radiology and radiation oncology
      graduates: training program directors' point of view.
AB  - OBJECTIVE: In light of concerns about the job market, we describe the employment
      situation for 1996 graduates and the status and plans of training programs.
      MATERIALS AND METHODS: In April-May 1996, and in a December follow-up, we
      surveyed all radiation oncology residency directors and a 50% random sample of
      diagnostic radiology residency directors about the employment situation of their
      1996 residency and fellowship graduates and about their programs. One hundred
      percent of those surveyed responded. We compared findings with similar 1995
      surveys. Differences were assessed with t tests, with a p value less than or
      equal to .05 as the test of significance. RESULTS: Unemployment 6 months after
      graduation was 0.8% for diagnostic fellows and less for other categories.
      Approximately 91% of graduates had positions that reasonably matched their
      training and personal employment goals. Our survey showed that programs have
      reduced beginning residency slots by 6% in diagnostic radiology and 4% in
      radiation oncology over the last 3 years. Program directors plan additional
      reductions of 3% and 29%, respectively, for total reductions in diagnostic
      radiology of 9% and in radiation oncology of 33%. Many observers were dismayed
      because of the low percentage of available slots that filled in the 1996 National
      Resident Matching Program. However, as in previous years, by late April to mid
      May 1996, more than 92% of beginning-year residency slots were filled.
      CONCLUSION: Unemployment continues to be low. "Soft" indicators such as the
      percentage of graduates with unsuitable positions show no deterioration. However,
      if major surpluses of diagnostic radiologists or radiation oncologists are
      pending, both the reductions in program size and the failure to fill all
      available slots are, to date, too minor to offer significant relief. Given the
      small size of actual reductions so far, the reported plans for large reductions
      of radiation oncologists seem questionable.

PMID- 9242733
TI  - Complications of central venous catheter placement.

PMID- 9242734
TI  - Communicating with the referring physician: the standard of care.
AB  - OBJECTIVE: This study sought to determine whether academic radiologists achieve
      the standard of care that the American College of Radiology recommends for
      communication of unexpected significant findings to referring physicians.
      CONCLUSION: Academic radiologists do achieve the recommended standard of care.

PMID- 9242735
TI  - The contemporary radiologist: consultant or film reader?

PMID- 9242736
TI  - Ground-glass opacity at CT: the ABCs.

PMID- 9242737
TI  - High-resolution CT of the lung: determination of the usefulness of CT scans
      obtained with the patient prone based on plain radiographic findings.
AB  - OBJECTIVE: We assessed the usefulness of chest radiographs for predicting whether
      high-resolution CT scans obtained with the patient prone would be valuable in
      assessing suspected diffuse lung disease. MATERIALS AND METHODS: In 100
      consecutive patients undergoing high-resolution CT, findings on plain chest
      radiographs were classified as normal, possibly abnormal, or abnormal. CT scans
      obtained with the patient supine were assessed for the presence and distribution
      of lung abnormalities without knowledge of the plain radiographic classification.
      A second review of the CT scans was done with equal numbers of scans obtained
      with the patient prone and with the patient supine. The usefulness of the CT
      scans obtained with the patient prone for detecting lung disease was determined
      and related to the plain radiographic classifications. RESULTS: High-resolution
      CT scans obtained with patients prone were helpful in excluding or confirming
      posterior lung abnormalities in 10 (28%) of 36 patients who had normal findings
      on chest radiographs, five (28%) of 18 patients who had possibly abnormal
      findings on chest radiographs, and only two (4%) of 46 patients who had abnormal
      findings on chest radiographs. The proportion of patients who benefited from high
      resolution CT scans obtained with the patient prone was significantly lower among
      the patients with abnormal findings on chest radiographs than among the patients
      with normal (p = .008) or possibly abnormal (p = .02) findings on chest
      radiographs. The two patients with abnormal findings on radiographs in whom CT
      scans obtained with the patient prone were helpful had minimal radiographic
      abnormalities. CONCLUSION: In patients with suspected diffuse lung disease,
      obtaining high-resolution CT scans with the patient prone may be useful when
      chest radiographs show normal findings, possibly abnormal findings, or minimal
      abnormalities indicative of diffuse lung disease. However, such scans are of
      little value in patients whose radiographs show abnormalities indicative of
      diffuse lung disease.

PMID- 9242738
TI  - High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of
      acute findings, reversibility of those findings, and clinical correlation.
AB  - OBJECTIVE: The aims of this study were threefold: to compare high-resolution CT
      (HRCT) of adult patients with cystic fibrosis (CF) during acute exacerbations
      with asymptomatic patients with CF, to evaluate reversibility of HRCT
      abnormalities after exacerbations, and to correlate HRCT with clinical
      parameters. SUBJECTS AND METHODS: Nineteen symptomatic and eight asymptomatic
      patients were prospectively evaluated by HRCT and pulmonary function tests
      (PFTs). Symptomatic patients were reassessed 2 weeks after the exacerbation.
      Studies were independently reviewed by two radiologists using a modified Bhalla
      scoring system, noting the presence, extent, and severity of bronchiectasis,
      peribronchial thickening, mucus plugging, and atelectasis or consolidation.
      Modifications to the Bhalla system included evaluation of the presence and
      profusion of centrilobular nodules and air-fluid levels within bronchiectatic
      cavities. The highest possible score was 24 points. Higher scores indicated
      greater severity. Mosaic perfusion was noted but not included in the modified
      Bhalla HRCT score. Total modified Bhalla HRCT score and components of the HRCT
      score were correlated with corresponding PFT parameters. RESULTS: Bronchiectasis,
      peribronchial thickening, mucus plugging, centrilobular nodules, and mosaic
      perfusion were identified in symptomatic and asymptomatic patients. Air-fluid
      levels in bronchiectatic cavities, identified in two patients, represented the
      only finding limited to acute exacerbation. Reversible findings included air
      fluid levels (100%), centrilobular nodules (36%), mucus plugging (33%), and
      peribronchial thickening (11%). Total HRCT severity scores of symptomatic and
      asymptomatic patients correlated with forced vital capacity (FVC) (r = .44, p =
      .01) and forced expiratory volume at 1 sec (FEV1) (r = .34, p = .04). Severity of
      bronchiectasis correlated with FVC (r = .50, p = .004) and FEV1 (r = .40, p =
      .02). Mucus plugging and centrilobular nodules did not correlate with PFT
      parameters. In the symptomatic patients, improvement in HRCT score correlated
      with changes in FEV1/FVC (r = .39, p = .049). CONCLUSION: Air-fluid levels in
      bronchiectatic cavities were the only parenchymal finding shown by HRCT that was
      limited to the acute exacerbation of CF in our study population. However, this
      finding was rare, being seen in two of 19 patients. Mucus plugging, centrilobular
      nodules, and peribronchial thickening were potentially reversible findings in
      symptomatic patients. HRCT accurately revealed disease severity in patients with
      CF. We also found that changes in HRCT scores correlated with clinical
      improvement as determined by PFTs.

PMID- 9242739
TI  - Biliary-pleural fistulas without biliary obstruction: percutaneous catheter
      management.
AB  - OBJECTIVE: Our purpose was to report the use of percutaneous catheter drainage as
      a therapeutic option in the management of three patients with biliary-pleural
      fistulas without biliary obstructions. CONCLUSION: In the proper clinical
      setting, the CT findings of liver dome laceration or abscess, diaphragm
      disruption, and pleural effusion should suggest biliary-pleural fistula.
      Percutaneous catheter management can be curative or serve a temporizing function
      before surgery.

PMID- 9242740
TI  - Imaging of ventricular assist devices and their complications.

PMID- 9242741
TI  - CT-assisted transbronchial needle aspiration: usefulness of CT fluoroscopy.

PMID- 9242743
TI  - Segmented K-space cine breath-hold cardiovascular MR imaging: Part 2. Evaluation
      of aortic vasculopathy.

PMID- 9242742
TI  - Segmented K-space cine breath-hold cardiovascular MR imaging: Part 1. Principles
      and technique.

PMID- 9242745
TI  - Staging of symptomatic primary breast cancer with MR imaging.
AB  - OBJECTIVE: This study was designed to investigate the accuracy of contrast
      enhanced MR imaging in the locoregional staging of symptomatic primary breast
      cancer and to determine the impact of contrast-enhanced MR imaging in planning
      surgical management. MATERIALS AND METHODS: Ninety patients with primary breast
      cancer (including two bilateral cancers) diagnosed and treated on the basis of
      conventional triple assessment (clinical, cytologic, and mammographic
      examination) underwent MR imaging at 1.0 T using a three-dimensional fast low
      angle shot T1-weighted pulse sequence before and after contrast enhancement. A
      short inversion time inversion recovery sequence was also obtained to evaluate
      the axilla of each patient. After resection, tumors were histopathologically
      mapped in detail and correlated with the extent of contrast enhancement on MR
      imaging. RESULTS: On the basis of triple assessment, 53 cancers were treated by
      wide local excision, of which 17 (32%) had positive margins at excision. Residual
      disease at reexcision was detected in eight of these 17 patients, a finding that
      correlated accurately with the extent of contrast enhancement on MR imaging. MR
      imaging was more accurate than mammography in determining invasive tumor size (r2
      = .93 versus r2 = .59), in depicting multifocality and extensive intraductal
      component (sensitivity, 81% versus 62%), and in assessing nipple-retroareolar
      complex. MR imaging-histopathologic correlation was possible in 75 axillae.
      Sensitivity and specificity for axillary node metastases were 90% and 82%,
      respectively. CONCLUSION: MR imaging of the breast has value in the preoperative
      locoregional staging of symptomatic primary breast cancer and is useful in
      planning a single definitive surgical resection in patients with breast cancer.

PMID- 9242744
TI  - Diagnostic performance characteristics of architectural features revealed by high
      spatial-resolution MR imaging of the breast.
AB  - OBJECTIVE: Our objective was twofold: to determine which architectural features
      revealed by high spatial-resolution MR imaging of the breast contribute to
      diagnostic accuracy and to evaluate the diagnostic performance characteristics of
      those architectural features. MATERIALS AND METHODS: Eligible patients with
      suspicious mammographic or palpable findings or both underwent MR imaging. Ninety
      three patients whose MR images revealed lesions that corresponded to the
      mammographically visible or palpable findings were included in the study.
      Patients were examined with sagittal T1-weighted spin-echo MR imaging, fat
      saturated T2-weighted fast spin-echo MR imaging, and dynamically enhanced fat
      saturated fast gradient-echo MR imaging. All patients underwent subsequent
      excisional biopsy or cyst aspiration. Lesions were identified initially by an
      experienced radiologist who was aware of the patient's clinical or mammographic
      information. Two radiologists who were unaware of the patients' histories and who
      had less experience in MR imaging of the breast then independently evaluated each
      lesion for the architectural-features and predicted each lesion's potential for
      malignancy. RESULTS: Architectural features that were highly predictive of benign
      disease included smooth or lobulated borders (97-100%), the absence of mass
      enhancement (100%), and enhancement that was less than the enhancement of
      surrounding breast fibroglandular tissue (93-100%). Nonenhancing internal
      septations were specific for the diagnosis of fibroadenoma. Architectural
      features that were highly predictive of malignant disease included spiculated
      borders (76-88%) and peripheral rim enhancement in the presence of central lesion
      enhancement (79-92%). CONCLUSION: Architectural features revealed by high spatial
      resolution MR imaging of the breast can help distinguish benign from malignant
      disease.

PMID- 9242746
TI  - Percutaneous repair of breast pseudoaneurysm: sonographically guided
      embolization.

PMID- 9242747
TI  - Stent implantation in patients with superior vena cava syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of using
      Wallstent implantation to treat superior vena cava syndrome due to malignant
      tumors. SUBJECTS AND METHODS: Digital subtraction angiography showed obstruction
      of the superior vena cava in 13 patients who then underwent transluminal
      dilatation and Wallstent implantation. The patients were treated with IV heparin
      and monitored in the emergency department. Thereafter, they were treated with a
      platelet inhibitor for 4 weeks. RESULTS: Because their signs and symptoms
      improved, patients were able to resume radiation therapy, chemotherapy, or both.
      One patient died of cardiac arrhythmia 1 day after stent placement. Although
      eight patients have subsequently died of their bronchial or thyroid gland tumors,
      superior vena cava syndrome did not recur in any patient. CONCLUSION:
      Percutaneous implantation of Wallstent endoprostheses provides excellent
      palliation for superior vena cava syndrome.

PMID- 9242748
TI  - Percutaneous ethanol sclerotherapy of postoperative lymphoceles.
AB  - OBJECTIVE: The purpose of this study was to describe our experience with ethanol
      sclerotherapy of postoperative lymphoceles. MATERIALS AND METHODS: We conducted a
      retrospective review of 32 patients who in a 6-year period underwent percutaneous
      ethanol sclerotherapy for the management of postoperative lymphoceles. Twenty
      three patients had undergone staging lymphadenectomy for malignant tumors, eight
      patients had undergone renal transplantation, and one patient had undergone
      vascular surgery. Of the 32 patients in the study group, eight (25%) had
      undergone previous aspiration or drainage, and three patients (9%) had undergone
      surgical lymphocelectomy. Patients were treated by percutaneous drainage under
      fluoroscopic, sonographic, or CT guidance. Sclerotherapy was done with absolute
      ethanol. Follow-up was conducted by review of clinical charts and imaging studies
      and by contacting the patient when necessary. RESULTS: Technical success was
      achieved in 30 patients (94%), with resolution of lymphocele shown by clinical
      and imaging findings. Treatment was unsuccessful in two patients (6%), and two
      patients (6%) had recurrences. Three patients (9%) subsequently underwent
      surgical treatment of the lymphoceles. Of these three patients, one had a
      lymphocele recur after surgery, which was then successfully treated with
      sclerotherapy. The average duration of catheter placement was 19 days.
      Complications, all minor, included catheter-related infections treated with
      antibiotics in three patients (9%) and catheter dislodgment that required
      repeated drainage procedures in two patients (6%). Clinical follow-up averaged 25
      months. CONCLUSION: Percutaneous ethanol sclerotherapy is a safe and effective
      treatment for postoperative lymphoceles. The technical success rate is high, the
      recurrence rate is low, and the complication rate is acceptable. Percutaneous
      sclerotherapy of lymphoceles is a less invasive alternative to surgical
      treatment.

PMID- 9242749
TI  - Treatment of malignant obstruction of the right ventricular outflow tract and
      pulmonary artery with metallic stents.

PMID- 9242750
TI  - High-resolution three-dimensional imaging from subsecond helical CT data sets:
      applications in vascular imaging.

PMID- 9242751
TI  - Recent epidural anesthesia: a relative contraindication to thrombolysis.

PMID- 9242752
TI  - Percutaneous ultrasonic lithotripsy in a patient with horseshoe kidney.

PMID- 9242753
TI  - Virtual colonoscopy: what will the issues be?

PMID- 9242754
TI  - TNM staging of pancreatic carcinoma using helical CT.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of helical CT
      scanning in predicting the stage of carcinoma of the exocrine pancreas using TNM
      staging guidelines and in predicting resectability of carcinoma of the exocrine
      pancreas. MATERIALS AND METHODS: Twenty-six patients with proven adenocarcinoma
      of the pancreas underwent uniphasic or biphasic helical CT scanning. Two
      observers unaware of the patient's surgical stage evaluated the CT examinations
      using the TNM system (with specific assessment and description of disease sites).
      In addition, the two observers rated confidence of nonresectability using a 5
      point scale (ranging from 1, definitely resectable, to 5, definitely not
      resectable). Observer results and preoperative interpretations were compared with
      surgical findings. RESULTS: Nineteen of 26 patients had nonresectable disease.
      The combined observer scores showed correct determination of T stage in 77% of
      patients, of N stage in 58%, and of M stage in 79%. The overall accuracy in
      determining lack of resectability was 96% and 84% for the two observers. All
      errors in determining resectable versus nonresectable disease occurred when the
      observer was not maximally confident of his or her diagnosis. CONCLUSION: Helical
      CT is an effective screening technique for assessing T and M stages of pancreatic
      carcinoma. However, helical CT is poor at detecting regional lymph node
      involvement. In patients with equivocal T-stage findings (such as questionable
      venous involvement), other studies such as endoscopic sonography may be of value.

PMID- 9242755
TI  - MR appearances of desmoid tumors in familial adenomatous polyposis.
AB  - OBJECTIVE: The purpose of this study was to investigate the ability of MR imaging
      to show desmoid tumors in patients with familial adenomatous polyposis, to
      document the appearances of these tumors, and to identify possible predictors of
      growth. SUBJECTS AND METHODS: CT and MR imaging of 15 patients with familial
      adenomatous polyposis and known abdominal wall or intraabdominal desmoid tumors
      were performed. Nine patients underwent follow-up CT and MR imaging, and four
      patients had undergone CT within the previous 12 months. Unenhanced and
      gadolinium-enhanced T1-weighted MR imaging sequences and T2-weighted MR imaging
      sequences were performed, as was unenhanced and IV contrast-enhanced helical CT.
      The CT and MR images were independently assessed. RESULTS: CT revealed 35 desmoid
      tumors: 22 were intraabdominal and 13 were in the abdominal wall. MR imaging
      revealed 21 of the 22 intraabdominal desmoid tumors and 13 of the 13 abdominal
      wall desmoid tumors. MR imaging and CT findings agreed precisely on the site and
      margin of the intraabdominal and abdominal wall desmoid tumors. CT was more
      effective in revealing their relationship to the bowel. Contrast enhancement was
      more easily identified on MR images than on CT scans, especially when enhancement
      was inhomogeneous. High signal intensity on T2-weighted images was seen in eight
      desmoid tumors, all of which showed significant growth on follow-up scans.
      CONCLUSION: MR imaging can show both intraabdominal and abdominal wall desmoid
      tumors in patients with familial adenomatous polyposis. High signal intensity on
      T2-weighted images was seen from desmoid tumors that had shown marked growth on
      follow-up imaging.

PMID- 9242756
TI  - Timed barium swallow: a simple technique for evaluating esophageal emptying in
      patients with achalasia.
AB  - OBJECTIVE: Our purpose was to define a simple technique for timing a barium
      swallow by which radiologists can assess esophageal emptying in patients with
      achalasia before and after minimally invasive therapy. Our purpose was also to
      determine the best method of quantifying the degree of emptying using this timed
      technique. MATERIALS AND METHODS: In the barium swallow technique, upright
      frontal spot films of the esophagus are obtained at 1, 2, and 5 min after
      ingestion of 100-200 ml of low-density (45% weight in volume) barium sulfate
      (volume of barium determined by patient tolerance). Forty-two of these barium
      swallows done by 23 patients with achalasia were retrospectively reviewed. The
      examination served either as a baseline study or as a 1-month follow-up study
      after patients had undergone pneumatic dilatation or Clostridium botulinum toxin
      injection. The spot films were digitized, and a region of interest was drawn
      around the column of barium by two observers. The change in area seen in the
      region of interest on the 1- and 5-min films served as the gold standard for
      percentage of emptying. The spot films were then analyzed by four other
      observers, each of whom independently, subjectively, and qualitatively estimated
      the percentage of emptying between the 1- and 5-min spot films. Percentages were
      divided into quintiles. On a separate occasion, each of these four observers also
      independently measured the height and width of the barium column on the 1- and 5
      min spot films. The product of height times width seen on the 1- and 5-min films
      became the quantitative estimate for percentage of emptying. RESULTS: We found no
      statistically significant difference between the percentage of emptying as
      measured on the digitized images by the two observers and the height-times-width
      calculations or qualitative emptying percentage as estimated by the four
      observers. Interobserver agreement for the area evaluated on the digitized films
      as well as the height-times-width measurements and qualitative estimates of
      emptying was almost perfect (the correlation coefficients being 0.99, 0.87, and
      0.93, respectively). CONCLUSION: The timed barium swallow is a simple and
      reproducible technique. Both qualitative assessment and estimated change in area
      based on height-times-width measurements of the barium column are accurate
      methods of estimating esophageal emptying.

PMID- 9242757
TI  - Herniation of the transverse colon after esophagectomy: is retrocardiac air a
      normal postoperative finding?
AB  - OBJECTIVE: This study describes the radiographic and CT imaging features of
      colonic herniation complicating esophagogastrectomy in three patients, all of
      whom required surgery. CONCLUSION: After routine esophagogastrectomy with gastric
      pull-through for esophageal carcinoma, the intrathoracic gastric pull-through
      most often lies in a right paraspinal location. Once a left-sided gastric pull
      through has been excluded, radiologists must be suspicious for left retrocardiac
      air lucency that possibly represents herniation of the nearby colon. Early
      diagnosis is important for the prevention of bowel strangulation, especially of
      the ischemia-susceptible splenic flexure.

PMID- 9242758
TI  - Triple-contrast CT interrogation of the retroperitoneal colon after a stab wound.

PMID- 9242759
TI  - Using endosonography to assess the effects of neoadjuvant therapy in patients
      with advanced esophageal cancer.
AB  - OBJECTIVE: The aim of this study was to determine the usefulness of
      endosonography for evaluating the effect of neoadjuvant therapy for advanced
      esophageal carcinoma. MATERIALS AND METHODS: Thirty-four patients with esophageal
      carcinoma (stage II, 16 patients; stage III, 18 patients) underwent various
      preoperative treatment. In all patients, endosonography was performed before and
      after treatment, and the percentage reduction in tumor size was calculated from
      the maximum area of the tumor. In the 27 patients who underwent surgery, the
      percentage reduction was compared with the pathologic response. Also, the overall
      survival rates were compared with the percentage reduction in tumor area.
      RESULTS: Reduction in tumor area ranged from 0% to 47%. The patients were divided
      into three groups according to the percentage reduction in tumor area. Pathologic
      response was graded according to the number of viable cells in the entire lesion.
      Correlation between pathologic response and percentage reduction in tumor area
      was strong. We found a significant difference in survival rates among the three
      groups. CONCLUSION: The percentage reduction in tumor area estimated by means of
      endosonography reflects the histologic effectiveness of neoadjuvant therapy in
      patients with advanced esophageal carcinoma and may enable clinicians to predict
      the prognosis of the disease.

PMID- 9242760
TI  - Biliary ascariasis.

PMID- 9242761
TI  - Clinical value of combined stents in esophageal cancer: combined use of Ultraflex
      and self-expanding zigzag metallic stents.

PMID- 9242762
TI  - A new technique of administration of oral contrast material for abdominal CT: the
      drip ingestion method.

PMID- 9242763
TI  - Symptomatic appendiceal wall thickening in an HIV-infected patient caused by
      interleukin-2 therapy.

PMID- 9242764
TI  - Upper gastrointestinal examination complicated by venous intravasation and portal
      vein thrombosis.

PMID- 9242765
TI  - Anatomy and clinical importance of cholecystic venous drainage: helical CT
      observations during injection of contrast medium into the cholecystic artery.
AB  - OBJECTIVE: The purpose of this study was to use helical CT to elucidate the
      anatomy and clinical importance of cholecystic venous drainage. SUBJECTS AND
      METHODS: We performed helical CT of the upper abdomen during injection of
      contrast medium through a superselectively catheterized cholecystic artery
      (cholecystic artery CT) in 28 patients, all of whom were surgical candidates for
      suspected hepatobiliary abnormality. In nine of these patients, CT during
      arterial portography (CTAP) was also performed. RESULTS: Cholecystic venous blood
      most frequently entered peripheral portal branches of hepatic segment V (27 of 28
      patients, 96%) and segment IV (26 of 28, 93%). In order of decreasing frequency,
      cholecystic venous blood also drained to segments I, VI, VIII, III, and VII.
      Cholecystic venous blood subsequently drained into the middle hepatic vein (21 of
      28, 75%) or right hepatic vein (20 of 28, 71%). In two patients with
      adenocarcinoma involving the gallbladder associated with multiple liver
      metastases, cholecystic venous drainage was seen around each metastatic focus. In
      the nine patients in whom both cholecystic artery CT and CTAP were performed,
      nontumorous portal perfusion defects were attributable to cholecystic venous
      drainage. CONCLUSION: Recognition of cholecystic venous drainage as a possible
      pathway for spread of disease from the gallbladder to the liver and also as one
      of the causes of non-tumorous portal perfusion defects seen on CTAP is important.

PMID- 9242766
TI  - Qualitative hepatic venous Doppler sonography versus portal flowmetry in
      predicting the severity of esophageal varices in hepatitis C cirrhosis.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of
      simple recognition of hepatic vein waveform abnormalities using Doppler
      sonography with portal Doppler flowmetry for the noninvasive assessment of
      esophageal varices in patients with hepatitis C cirrhosis. SUBJECTS AND METHODS:
      Fifty patients with biopsy-proven liver cirrhosis caused by hepatitis C who were
      being examined for possible liver transplantation were studied prospectively with
      Doppler sonography by a single observer. Hepatic vein waveforms were classified
      as normal triphasic, abnormal biphasic, monophasic, and those with loss of the
      reverse-flow component. Portal flow indicators included the maximum values of
      portal flow velocity, portal vein flow volume, diameter of the portal vein, and
      congestion index. For the purposes of this study, we simplified the endoscopic
      grading of varices by classifying F1 and F2 varices as small and F3 as large.
      None of the patients had clinical or echocardiographic signs of failure of the
      right side of the heart. RESULTS: Sensitivity for the detection of large varices
      was 92% for monophasic waves, 76% for waves with loss of the reverse flow
      component, and 62% for biphasic waves. Overall specificity was 100%. Portal vein
      diameter and congestion index were higher (p < .02) and portal vein velocity was
      lower (p < .05) in patients with varices than in patients without varices, but
      these indicators were not useful in determining the size of varices. Portal vein
      flow volume did not differ in the presence of varices or ascites and was
      independent of the morphology of the hepatic vein wave. CONCLUSION: Simple
      recognition of patterns seen in hepatic vein waveform morphology in patients with
      liver cirrhosis caused by hepatitis C is superior to portal Doppler flowmetry for
      predicting the size of esophageal varices.

PMID- 9242767
TI  - ERCP and CT findings of ectopic drainage of the common bile duct into the
      duodenal bulb.
AB  - OBJECTIVE: The purpose of this study was to evaluate ERCP and CT findings of
      ectopic drainage of the common bile duct into the duodenal bulb. CONCLUSION:
      Although rare, the diagnosis of ectopic drainage of the common bile duct into the
      duodenal bulb is important to prevent inadvertent damage during biliary tract or
      gastric surgery and to clarify the cause of chronic peptic ulcers.

PMID- 9242768
TI  - CT detection of retroperitoneal lymph node metastases in patients with clinical
      stage I testicular nonseminomatous germ cell cancer: assessment of size and
      distribution criteria.
AB  - OBJECTIVE: Patients with nonseminomatous germ cell cancer of the testis with no
      evidence of metastatic disease after orchiectomy may be managed with either
      retroperitoneal lymph node dissection or surveillance. The present retrospective
      study was undertaken to determine the accuracy of CT for revealing
      retroperitoneal lymph node metastases in patients with newly diagnosed clinical
      stage 1 testicular nonseminomatous germ cell cancer of the testis when smaller
      size criteria (smaller than 10 mm) are applied and to test the hypothesis that CT
      revealed anterior retroperitoneal lymph nodes are more likely to correlate with
      metastases than are posterior lymph nodes. MATERIALS AND METHODS: Abdominal CT
      scans obtained before surgery in 70 patients were reviewed by three observers who
      were unaware of the results of retroperitoneal lymphadenectomy. The sizes and
      sites of all lymph nodes measuring larger than or equal to 4 mm were recorded.
      Each CT scan was judged as positive or negative for retroperitoneal metastasis on
      the basis of the size of the largest measured lymph node at the expected
      metastatic site. Diameters of 4, 6, 8, and 10 mm were successively applied to
      each case as the criteria for a positive scan. RESULTS: Using a criterion of 10
      mm or larger for metastases, we calculated a sensitivity of 37% and a specificity
      of 100%; with a 4-mm criterion, the sensitivity was 93% and the specificity was
      58%. Receiver operating characteristic curves comparing the accuracy of CT for
      revealing similar-sized lymph nodes located anterior or posterior to a line
      bisecting the aorta differed significantly (p = .04) when the same criteria were
      applied to lymph nodes in both regions. CONCLUSION: False-negative rates were
      decreased from 63% using a size criterion of 10 mm to as low as 7% using a size
      criterion of 4 mm, with a corresponding decrease in specificity. Lymph nodes
      measuring larger than or equal to 4 mm, especially those located anterior to the
      mid portion of the aorta, should raise a suspicion of metastases.

PMID- 9242769
TI  - Cholesterol crystals in hydroceles: sonographic detection and possible
      significance.
AB  - OBJECTIVE: The aim of this study of seven patients who had elective surgical
      repairs of a hydrocele was to try to differentiate by microscopy and chemical
      analysis hyperechoic hydrocele fluid from the more typical anechoic hydrocele
      fluid. CONCLUSION: Hyperechoic hydrocele fluid is related to the presence of
      cholesterol crystals. Cholesterol crystals were noted on microscopic examination
      in all three patients with hyperechoic hydrocele fluid. No cholesterol crystals
      were evident in the four patients with typical anechoic hydrocele fluid.

PMID- 9242770
TI  - Mullerian mixed tumors: CT characteristics with clinical and pathologic
      observations.
AB  - OBJECTIVE: This retrospective study analyzed the CT characteristics of mullerian
      mixed tumors. Clinical aspects, outcomes, and pathologic correlations were also
      evaluated. CONCLUSION: Mullerian mixed tumor is a rapidly growing aggressive
      tumor with a relatively poor prognosis. Uterine and metastatic masses showed
      central low attenuation. Metastatic masses often had irregular enhancement
      centrally and surface enhancement circumferentially. The tendency toward local
      and lymphatic spread and intraperitoneal seeding was greater than the tendency
      toward hematogenous metastases. CT was useful before surgery in defining the
      extent of disease and for follow-up clinical management in identifying metastases
      and assessing treatment effectiveness.

PMID- 9242771
TI  - Examination of renal donors as outpatients using intraarterial digital
      subtraction angiography and a pigtail catheter.
AB  - OBJECTIVE: We performed this study to assess the safety and efficacy of
      outpatient angiographic renal donor examination using a 3-French pigtail
      catheter, intraarterial digital subtraction angiography, and a progressively
      shortened examination time after the procedure. CONCLUSION: For 45 consecutive
      procedures performed, no complications were reported, and no diagnostic
      discrepancies were found in patients who proceeded to surgery. Using this method
      we were also able to eliminate the excretory urogram as well as reduce the total
      amount of contrast per procedure.

PMID- 9242772
TI  - Critical uses of intraoperative gynecologic sonography.

PMID- 9242773
TI  - Uterine leiomyoma appearing as an inguinal mass.

PMID- 9242774
TI  - Change in the composition of adrenal nodules after therapy as revealed by opposed
      phase MR imaging.

PMID- 9242775
TI  - Angioplasty treatment of portal vein stenosis in children with segmental liver
      transplants: mid-term results.
AB  - OBJECTIVE: Percutaneous venoplasty has showed excellent technical success and
      excellent early results in treating portal vein stenoses in children with reduced
      size liver transplants. We review the mid-term results in 22 children in whom
      portal venoplasty was attempted. SUBJECTS AND METHODS: During 27 months,
      percutaneous transhepatic portal venoplasty was attempted in 22 children with
      portal vein stenoses. Patients presented with symptoms of portal vein
      hypertension or were identified by routine surveillance with posttransplantation
      Doppler sonography. All stenoses were verified with angiography. Venoplasty was
      performed by direct puncture of an intrahepatic portal vein before balloon
      angioplasty of the stenotic segment. Patients were followed up with sonographic
      surveillance, and reintervention was performed as needed. In patients who had
      suboptimal results after portal venoplasty or who developed recurrent stenoses,
      intravascular stents were placed across stenoses. RESULTS: In 16 of 22 patients,
      initial clinical and technical success was achieved. In the six patients who
      underwent unsuccessful procedures, complete occlusion of the portal vein
      precluded access to the extrahepatic portal vein. Of the 16 patients who
      underwent successful procedures, intravascular stents were placed at the time of
      initial venoplasty in five patients for elastic stenosis. In seven other
      patients, portal vein restenosis occurred after venoplasty (mean, 6.3 months),
      necessitating intravascular stent placement. Four patients who underwent
      successful venoplasty without stent placement have required no further
      intervention. Portal vein patency has been maintained in all 16 patients who
      underwent technically successful procedures for 4-29 months (mean, 20 months).
      CONCLUSION: In children with reduced-size liver transplants who experience
      delayed portal vein stenosis, percutaneous transhepatic portal venoplasty has
      achieved encouraging mid-term results. It is the procedure of choice in our
      hospital and often eliminates the need for surgical revision, portacaval
      shunting, or retransplantation.

PMID- 9242776
TI  - Soft-copy versus hard-copy cranial sonography: intraobserver agreement and
      workstation efficiency.
AB  - OBJECTIVE: The objective of the study was to determine the intraobserver
      agreement, confidence level, and efficiency in interpretation of soft-copy
      (workstation) versus hard-copy (laser-printed film) sonograms of the cranium.
      MATERIALS AND METHODS: Cranial sonograms of 100 premature infants were randomly
      reviewed twice on both soft-copy and hard-copy images by three observers and were
      graded for hemorrhage using a five-level scale. The kappa statistic was
      calculated to measure intraobserver agreement. Differences in agreement were
      tested for statistical significance with a test for marginal homogeneity.
      Observers rated their confidence in interpretation using a six-point ordinal
      scale. Total viewing time was recorded, and videotaped sessions were analyzed for
      image handling time (opening each case, closing each case, and selecting the next
      case) and interpretation time. RESULTS: For soft copy versus hard copy, the mean
      kappa value was .73; for hard-copy 1 versus hard-copy 2, .71; and for soft-copy 1
      versus soft-copy 2, .65. None of these differences was statistically significant
      (p > .05). The mean confidence score was the same for soft copy (5.3) and hard
      copy (5.3). On average, the observers needed 24 min longer to review 100 studies
      on soft copy than on hard copy. Opening and closing times for soft copy were
      significantly faster than for hard copy (p = .0001); however, case selection for
      soft copy, which was not needed for hard copy, took 4.69-9.09 sec per case.
      Extrapolated to 100 cases, case selection accounted for 8-15 min of viewing time.
      CONCLUSION: Radiologist agreement and confidence in the interpretation of cranial
      sonograms for hemorrhage was the same for soft copy and hard copy. However,
      viewing times were longer for soft copy. Elimination of inefficiency in case
      selection could improve image-handling time.

PMID- 9242777
TI  - Neurenteric cyst shown by prenatal sonography.

PMID- 9242778
TI  - A simplified method for repositioning distally migrated ureteral stents.

PMID- 9242779
TI  - Evaluation of contrast densities in the diagnosis of carotid stenosis by CT
      angiography.
AB  - OBJECTIVE: This study assesses intravascular density produced by ionic and
      nonionic contrast material and its effect on visualization of stenoses by CT
      angiography. MATERIALS AND METHODS: CT angiography was performed using a 32
      vessel phantom to study grades of luminal stenoses (0-100%), three lengths of
      stenoses (1, 3, and 5 mm), and two angles of inclination into the stenoses (45
      degrees and 75 degrees). Scans were obtained with a slice thickness of 2 mm, a
      slice interval of 1.5 mm, a pitch of 1.0, a voltage of 120 kV, and a current of
      both 100 and 200 mA. Vessels were oriented parallel to the z-axis, and opacified
      with ionic and nonionic contrast material that had densities of 100, 150, 200,
      250, 300, and 350 H. Cross-sectional luminal diameters were measured in and out
      of the stenoses. Edge definition and halo artifact for each vessel were graded by
      an investigator who was unaware of the contrast material density used. RESULTS: A
      contrast density of 150 H as revealed by CT angiography yielded the most accurate
      stenosis measurements with ionic contrast material. For nonionic contrast
      material, attenuation values of 150 and 200 H produced the best results on CT
      angiography. A density of 100 H or greater than 250 H significantly increased the
      error of vessel measurement (p = .001) for both types of contrast material. For
      the two current levels tested (100 and 200 mA), no statistical difference was
      found. CONCLUSION: The accuracy of CT angiography in measuring carotid stenosis
      depends on the luminal attenuation value. An optimum contrast density is 150 H
      for ionic contrast material; for nonionic contrast material, 150-200 H (at the
      window and level settings of 300 H and 40 H).

PMID- 9242781
TI  - Horner's syndrome due to first-order neuron lesions of the oculosympathetic
      pathway.

PMID- 9242780
TI  - Localization of language cortices by functional MR imaging compared with
      intracarotid amobarbital hemispheric sedation.
AB  - OBJECTIVE: We undertook this study to investigate functional MR imaging as a new
      clinical method for determining hemispheric language dominance. Seven patients
      undergoing surgical evaluation for chronic intractable epilepsy were studied.
      Intracarotid amobarbital injection was also performed and the findings compared
      with the functional MR imaging results. CONCLUSION: Functional MR imaging studies
      enabled localization of the frontal and temporal lobe language cortices. The
      results of functional MR imaging and intracarotid amobarbital testing of
      hemispheric language dominance agreed in all seven patients, including two right
      handed patients with right-hemisphere language dominance. These preliminary
      results show that functional MR imaging is an accurate noninvasive method of
      determining language dominance that may replace the amobarbital test for some
      purposes if confirmed by additional research.

PMID- 9242782
TI  - The peroneocalcaneus internus muscle: MR imaging features.
AB  - OBJECTIVE: The peroneocalcaneus internus muscle is a rare muscle of the posterior
      calf that to our knowledge has not been reported in the radiology literature. The
      purpose of our study was to describe the normal anatomy and MR characteristics of
      this muscle in eight patients in whom the muscle was identified. CONCLUSION: The
      peroneocalcaneus internus muscle is a rare muscle that originates from the inner
      aspect of the distal fibula, descends within the tarsal tunnel, and inserts on a
      small tubercle in the calcaneus, just distal to the sustentaculum tali. The
      muscle may displace the flexor hallucis longus muscle medially and thus
      indirectly encroach on the neurovascular bundle.

PMID- 9242783
TI  - Lipoma and liposarcoma: evaluation using CT and MR imaging.

PMID- 9242784
TI  - Direct visualization of peritumoral rims.

PMID- 9242785
TI  - E-mail and the law.

PMID- 9242786
TI  - Re: Physicians' opinions on the delivery of mammographic screening services.

PMID- 9242787
TI  - Appropriate use of significant figures.

PMID- 9242788
TI  - Risk-to-benefit ratio of Swan-Ganz catheterization.

PMID- 9242789
TI  - Re: Effect of hydration status on renal medulla attenuation on unenhanced CT
      scans.

PMID- 9242790
TI  - CT of ameloblastic fibroodontoma.

PMID- 9242791
TI  - Venous hemangioma of the mesocolon.

PMID- 9242793
TI  - Putting public health back into epidemiology.

PMID- 9242792
TI  - CT appearance of esophagobronchial fistula: a clue to lung sequestration.

PMID- 9242794
TI  - Distinguishing between response to HIV vaccine and response to HIV.

PMID- 9242795
TI  - Explaining inequalities in coronary heart disease.

PMID- 9242796
TI  - Guidelines on drug treatments for Alzheimer's disease.

PMID- 9242797
TI  - 30 years of penicillin-resistant S pneumoniae: myth or reality?

PMID- 9242798
TI  - Will the UK cope?

PMID- 9242799
TI  - Contribution of job control and other risk factors to social variations in
      coronary heart disease incidence.
AB  - BACKGROUND: The first Whitehall Study showed an inverse social gradient in
      mortality from coronary heart disease (CHD) among British civil servants--namely,
      that there were higher rates in men of lower employment grade. About a quarter of
      this gradient could be attributed to coronary risk factors. We analysed 5-year
      CHD incidence rates from the Whitehall II study to assess the contribution to the
      social gradient of psychosocial work environment, social support, coronary risk
      factors, and physical height. METHODS: Data were collected in the first three
      phases of examination of men and women in the Whitehall II study. 7372 people
      were contacted on all three occasions. Mean length of follow-up was 5.3 years.
      Characteristics from the baseline, phase 1, questionnaire, and examination were
      related to newly reported CHD in people without CHD at baseline. Three self
      reported CHD outcomes were examined: angina and chest pain from the Rose
      questionnaire, and doctor-diagnosed ischaemia. The contribution of different
      factors to the socioeconomic differences in incident CHD was assessed by
      adjustment of odds ratios. FINDINGS: Compared with men in the highest grade
      (administrators), men in the lowest grade (clerical and office-support staff) had
      an age-adjusted odds ratio of developing any new CHD of 1.50. The largest
      difference was for doctor-diagnosed ischaemia (odds ratio for the lowest compared
      with the highest grade 2.27). For women, the odds ratio in the lowest grade was
      1.47 for any CHD. Of factors examined, the largest contribution to the
      socioeconomic gradient in CHD frequency was from low control at work. Height and
      standard coronary risk factors made smaller contributions. Adjustment for all
      these factors reduced the odds ratios for newly reported CHD in the lowest grade
      from 1.5 to 0.95 in men, and from 1.47 to 1.07 in women. INTERPRETATION: Much of
      the inverse social gradient in CHD incidence can be attributed to differences in
      psychosocial work environment. Additional contributions were made by coronary
      risk factors--mainly smoking--and from factors that act early in life, as
      represented by physical height.

PMID- 9242800
TI  - A nested case-control study of non-Hodgkin lymphoma and serum organochlorine
      residues.
AB  - BACKGROUND: The steady worldwide increase in the incidence of non-Hodgkin
      lymphoma during the past few decades remains mostly unexplained. Several studies
      suggest that there may be an association between the agricultural use of the
      organochlorine 1,1,1-trichloro-2,2'bis(p-chlorophenyl)ethane (DDT) and increased
      risk of non-Hodgkin lymphoma. We have investigated the association between risk
      of non-Hodgkin lymphoma and body burden of selected organochlorines in the
      general population in a nested case-control study. METHODS: We measured
      prediagnostic serum concentrations of DDT, its metabolites, and other
      organochlorines, including polychlorinated biphenyls (PCBs), in 74 cases of non
      Hodgkin lymphoma and 147 matched controls identified from a prospective cohort of
      25,802 adults, established in 1974 in Washington County, Maryland, USA. We report
      results for total lipid-corrected serum concentrations of DDT and total PCBs.
      FINDINGS: There was a strong dose-response relation between quartiles of total
      lipid-corrected serum PCB concentrations and risk of non-Hodgkin lymphoma overall
      (odds ratios by quartile: 1.0; 1.3 [95% CI 0.5-3.3]; 2.8 [1.1-7.6]); and 4.5 [1.7
      12.0]; p for trend = 0.0008) and separately in men and in women. There was also
      evidence suggesting that seropositivity for the Epstein-Barr virus early antigen
      potentiated the effects of serum PCBs. By contrast, total lipid-corrected serum
      concentrations of DDT were not associated with risk of non-Hodgkin lymphoma.
      INTERPRETATION: These results should be regarded as hypothesis-generating. Before
      causal inferences can be made about exposure to PCBs and increased risk of non
      Hodgkin lymphoma, our findings require replication and the biological
      plausibility of the association needs further investigation.

PMID- 9242801
TI  - HIV-1 disease progression and AIDS-defining disorders in rural Uganda.
AB  - BACKGROUND: The majority of people infected with HIV-1 live in Africa, yet little
      is known about the natural history of the disease in that continent. We studied
      survival times, disease progression, and AIDS-defining disorders, according to
      the proposed WHO staging system, in a population-based, rural cohort in Uganda.
      METHODS: In 1990 we recruited a random sample of people already infected with HIV
      1 (as prevalent cases) detected during the initial survey round of a general
      population study to form a natural-history cohort. Individuals from the general
      population cohort who seroconverted between 1990 and 1995 (incident cases) were
      also invited to enroll. Participants were seen routinely every 3 months and when
      they were III. FINDINGS: By the end of 1995, 93 prevalent cases and 86 incident
      cases had been enrolled. Four patients in the prevalent group were in stage 4
      (AIDS) at the initial visit. During the next 5 years, 37 prevalent cases
      progressed to AIDS. Seven incident cases progressed to AIDS and the cumulative
      progression to AIDS at 1, 3, and 5 years after seroconversion was 2%, 6%, and
      22%, respectively. The cumulative probability of AIDS at 4 years from entering
      stages 1, 2, and 3 was 11%, 33%, and 58%, respectively. There were 47 deaths
      among prevalent cases and seven among incident cases during follow-up. The
      cumulative mortality 4 years after patients entered stages 1, 2, 3, and 4 was 9%,
      33%, 56%, and 86%, respectively. The median survival after the onset of AIDS was
      9.3 months. INTERPRETATION: Our results are important for the setting of
      priorities and rationalisation of treatment availability in countries with poor
      resources. We found that progression rates to AIDS are similar to those in
      developed countries for homosexual cohorts and greater than for cohorts infected
      by other modes of transmission. However, we have found that the rates of all
      cause mortality are much higher and the progression times to death are shorter
      than in developed countries.

PMID- 9242802
TI  - Medical end-of-life decisions made for neonates and infants in the Netherlands.
AB  - BACKGROUND: Advances in neonatal intensive care have lowered the neonatal death
      rate. There are still some severely ill neonates and infants, however, for whom
      the application of all possible life-prolonging treatment modalities may be
      questioned. METHODS: We did two studies in the Netherlands. In the first we sent
      questionnaires to physicians who had attended 338 consecutive deaths (August
      November, 1995) within the first year of life (death-certificate study), and in
      the second we interviewed 31 neonatologists or paediatric intensive-care
      specialists and 35 general paediatricians. The response rates were 88% and 99%,
      respectively. FINDINGS: In the death-certificate study, 57% of all deaths had
      been preceded by a decision to forgo life-sustaining treatment; this decision was
      accompanied by the administration of potentially life-shortening drugs to
      alleviate pain or other symptoms in 23%, and by the administration of drugs with
      the explicit aim of hastening death in 8%. A drug was given explicitly to hasten
      death to neonates not dependent on life-sustaining treatment in 1% of all death
      cases. No chance of survival was the main motive in 76% of all end-of-life
      decisions, and a poor prognosis was the main motive in 18%. The interview study
      showed that parents had been involved in making 79% of decisions. The physicians
      consulted colleagues about 88% of decisions. Most paediatricians favoured formal
      review of medical decisions by colleagues together with ethical or legal experts.
      INTERPRETATION: Death among neonates and infants is commonly preceded by medical
      end-of-life decisions. Most Dutch paediatricians seem to find prospects for
      survival and prognostic factors relevant in such decisions. Public control by a
      committee of physicians, paediatricians, ethicists, and legal experts is widely
      endorsed by paediatricians.

PMID- 9242803
TI  - Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a
      result of false-positive PCR.
AB  - BACKGROUND: In the USA, more than 2000 volunteers have received one or more
      experimental HIV-1 vaccines in phase I and II clinical trials, and there have
      been breakthrough HIV-1 infections among participants receiving vaccine and
      placebo. Serological diagnosis of new HIV-1 infections in vaccine-trial
      participants will become increasingly complicated as more viral components are
      used in vaccines. Recognition of this problem has led to a reliance on viral
      genome measurement to distinguish vaccine-induced immunity from HIV-1 infection.
      Currently, quantitative RNA measurement is expensive, prone to contamination, and
      reliable only in laboratories certified by manufacturers or that have quality
      control programmes. METHODS: A high-risk vaccinee presented after an acute
      febrile episode and was tested for HIV-1 infection by reverse transcriptase (RT)
      PCR of viral RNA. Further extensive tests were required to clarify the HIV-1
      infection and immune status of the vaccinee, including repeat RT-PCR, nested DNA
      PCR, western blot, lymphoproliferation assay, cytotoxic T-cell lysis, CD8
      depleted co-culture, and HIV-1 challenge culture. FINDINGS: Initial testing of
      plasma by RNA RT-PCR was reported as positive. This result was not confirmed by
      viral cultures, nested DNA PCR, western blot, or EIA. Additional RNA RT-PCR
      assays gave positive results from earlier occasions in the vaccine trial.
      Eventually, testing of all previously reactive samples by RNA RT-PCR was repeated
      in a quality-controlled laboratory, and confirmed the negative HIV-1 status of
      the individual. INTERPRETATION: This case report exemplifies the difficulties
      with use of viral-genome measurement as a screening test to diagnose HIV-1
      infection, particularly in individuals who have ever participated in HIV-1
      vaccine trials. Monitoring of large numbers of phase III vaccinees by RNA RT-PCR
      will not be feasible. The design of efficacy trials for new vaccines should be in
      parallel with development of antibody-based diagnostic tests that are capable of
      differentiating between immunisation and true HIV-1 infection.

PMID- 9242804
TI  - A surgeon with a nasty taste in his mouth.

PMID- 9242805
TI  - New treatments and azathioprine in multiple sclerosis.

PMID- 9242806
TI  - Inflammatory bowel disease activity measured by positron-emission tomography.

PMID- 9242807
TI  - Cholinergic autoantibodies in sinus-node dysfunction.

PMID- 9242808
TI  - Treatment of prepubertal gonadotrophin-deficient boys with recombinant human
      follicle-stimulating hormone.

PMID- 9242809
TI  - Detection of gene deletion in single metastatic tumour cells in lymphnode tissue
      by fluorescent in-situ hybridisation.

PMID- 9242811
TI  - Yellow palms with disulfiram.

PMID- 9242810
TI  - Use of a cyclo-oxygenase type-2-selective non-steroidal anti-inflammatory agent
      to prevent preterm delivery.

PMID- 9242812
TI  - Amenorrhoea.

PMID- 9242813
TI  - Radiological sciences, past and present.
AB  - Few observations can have been as rapidly and widely disseminated in medicine as
      the diagnostic X-ray (radiograph). The first few decades after Rontgen's
      discovery saw technical developments that made radiography more practical,
      quicker, safer for both imager and patient, and able to achieve greater contrast.
      This article reviews the history of imaging but it also looks to the future and
      begins to open up some of the issues that radiology faces in the 21st century-
      issues that the next six articles in this Lancet series will enlarge upon. The
      conventional radiograph remains the most common medical image but a host of new
      techniques have come along. Are they research tools, clinical methods, or both-
      and how, in an age of sensitivity about the costs of health care, do they stand
      up?

PMID- 9242814
TI  - HIV and AIDS in southeast Asia.

PMID- 9242815
TI  - Selective serotonin reuptake inhibitors plus pindolol.

PMID- 9242816
TI  - Selective serotonin reuptake inhibitors plus pindolol. The REEP.

PMID- 9242817
TI  - Selective serotonin reuptake inhibitors plus pindolol.

PMID- 9242818
TI  - Hepatitis-E-associated fulminant hepatic failure in non-pregnant young women.

PMID- 9242819
TI  - EMEA and third-generation oral contraceptives.

PMID- 9242820
TI  - Home blood-pressure control in Japanese hypertensive population.

PMID- 9242821
TI  - Efficacy of camptothecin in progressive multifocal leucoencephalopathy.

PMID- 9242822
TI  - Mania.

PMID- 9242823
TI  - Effect of low-molecular-weight heparin on serum concentrations of potassium.

PMID- 9242824
TI  - Relation between endothelial-cell activation and infection, inflammation, and
      infarction.

PMID- 9242825
TI  - Relation between endothelial-cell activation and infection, inflammation, and
      infarction.

PMID- 9242826
TI  - Tick toxicant.

PMID- 9242827
TI  - Different criteria for pharmacological and surgical treatment of hypertension.

PMID- 9242828
TI  - Cystic fibrosis and anaemia in infancy.

PMID- 9242829
TI  - Smoking and Alzheimer's disease.

PMID- 9242830
TI  - Care for dying patients.

PMID- 9242831
TI  - Care for dying patients.

PMID- 9242832
TI  - Palliative medicine in cancer.

PMID- 9242833
TI  - Tokyo subway gas attack.

PMID- 9242834
TI  - Collections of cord blood.

PMID- 9242835
TI  - Auguste D and Alzheimer's disease.

PMID- 9242836
TI  - Auguste D and Alzheimer's disease.

PMID- 9242837
TI  - Diarrhoea and double vision.

PMID- 9242838
TI  - Medical pluralism in rural India.

PMID- 9242839
TI  - How are nations trying to prevent suicide? An analysis of national suicide
      prevention strategies.
AB  - Recent increases in suicide rates internationally have focused attention on
      suicide as an important area of public health concern. In this review, strategies
      developed by various countries to halt this trend are compared. Nine out of 15
      countries respond to enquiry about the state of development of suicide prevention
      strategies and programmes. Comprehensive strategies have been or are being
      developed by Finland, Norway, Australia, New Zealand and Sweden. The organization
      of these strategies differs between countries. The interventions have similar
      targets and are presented in detail There are some similarities in strategy
      content but evident differences in organization. Further developments should not
      only be based on research, but also consider the diverse experiences of other
      countries, and they should incorporate appropriate structures for monitoring and
      evaluation.

PMID- 9242840
TI  - A survey of the attitudes of chronic psychiatric patients living in the community
      toward their medication.
AB  - Because non-compliance with antipsychotic drug therapy is both common and
      associated with a substantially increased risk of acute relapse, depot medication
      must be preferred for most schizophrenic out-patients. Yet there is a perception
      that depot medication is unpopular among patients. In the survey of out-patients
      reported here, the great majority of patients receiving either oral or depot
      neuroleptics (with or without oral augmentation) would, given a free choice,
      elect to continue with their present dose form (94% and 87%, respectively). In
      virtually all cases, the choice of route was made by the treating physician and
      readily accepted by the patient. These findings suggest that physicians should
      more often recommend and prescribe depot medication when antipsychotic
      maintenance therapy is indicated.

PMID- 9242841
TI  - The Shona Symptom Questionnaire: the development of an indigenous measure of
      common mental disorders in Harare.
AB  - The objective of this study was to develop an indigenous measure of common mental
      disorders (CMD) in the Shona language in Zimbabwe. Ethnographic and qualitative
      studies elicited idioms of distress of mental disorder leading to the preliminary
      Shona Symptom Questionnaire (SSQ), and items from the Self-Report Questionnaire
      (SRQ) were added to it. The 56-item Preliminary Shona Symptom Questionnaire
      (PSSQ) was administered to 302 randomly selected primary care attenders, of whom
      100 were classified as cases on the basis of agreement between care provider
      assessment and a psychiatric interview. Discriminant analysis identified 14 items
      that were the strongest predictors of mental disorder. The 14-item SSQ has a high
      level of internal consistency (Cronbach's alpha = 0.85). The items are a mixture
      of emic and etic phenomena. The total score correlates strongly with patients'
      self-assessment of the emotional nature of their illness. Satisfactory
      specificity and sensitivity occurred at a cut-off point of 7/8. The SSQ is the
      first indigenous measure of mental disorder developed in sub-Saharan Africa to
      have included idioms or distress of primary care attenders and involved patients
      consulting traditional medical practitioners. It promises to be a useful
      instrument for epidemiological and clinical research. The methodology used is an
      innovative way of combining etic and emic methods in the evaluation of CMD.

PMID- 9242842
TI  - Are immunological markers, social and personal resources, or a complaint-free
      state predictors of progression among HIV-infected patients?
AB  - Predictors of disease progression were studied in 89 asymptomatic HIV-infected
      patients who were prospectively evaluated for psychosocial variables and the
      development of clinical symptoms over a period of 2 years. The subjects were
      assessed for symptoms, laboratory measures, demographic variables, social and
      personal resources, mental status, alcohol, nicotine and drug use, sexual
      activity and risk behaviour, and sexually transmitted diseases. After 1 year, 17%
      of the patients had developed HIV-associated symptoms (symptomatic disease or
      AIDS), and after 2 years, 32% had developed symptoms or had died. In the
      multivariate analyses, the baseline CD4 count was the only significant predictor
      of disease progression during both observation periods. Psychosocial measures did
      not predict the progression of HIV infection.

PMID- 9242843
TI  - Efficacy of venlafaxine in depressive illness in general practice.
AB  - A double-blind, placebo-controlled study of 229 patients with a Research
      Diagnostic Criteria diagnosis of major, minor or intermittent depression was used
      to compare the clinical profiles of venlafaxine and imipramine in general
      practice. Venlafaxine produced a significant improvement compared to placebo in
      symptoms of depression and anxiety as rated by the total MADRS and percentage of
      responders, the CGI improvement, the CGI severity of illness, the BSA psychic
      anxiety item and the HSCL. On a number of these measures, venlafaxine was also
      significantly more effective than imipramine. Venlafaxine was significantly
      superior to both imipramine and placebo for the SARS total score and the items
      'social/leisure' and 'extended family.' A similar proportion of patients
      discontinued treatment in each group, but fewer patients on venlafaxine
      discontinued treatment because of an unsatisfactory response.

PMID- 9242844
TI  - Changing patterns of distress during the adjustment of recent immigrants: a 1
      year follow-up study.
AB  - A sample of 419 recent immigrants from the former Soviet Union to Israel was
      assessed, with a 1-year follow-up of 199 of these subjects. The Immigration
      Related Stressors Scale, Talbieh Brief Distress Inventory and Multidimensional
      Scale of Perceived Social Support were employed to measure the level and sources
      of distress, as well as the sources of social support. Three major patterns of
      change in distress level were distinguished, and their 1-year prevalence rates
      were established. In total, 44% of the respondents demonstrated the 'normal'
      pattern, with a permanent low distress level, 33% displayed the 'positive'
      pattern, with either persistent moderate or decreasing distress, and 23%
      displayed the 'negative' pattern, with either persistent high or increasing
      distress. Among the immigrants who demonstrated the positive pattern of change in
      distress, rates of stressors such as 'anxiety about the future', 'uncertainty in
      the present', 'depressive state', 'insufficient knowledge of Hebrew' and
      'malevolence of Israelis' decreased during the study period. In those who showed
      the negative pattern, rates of stressors such as 'personality characteristics'
      and 'lack of acceptance of the host culture/mentality' have increased. Immigrants
      who showed the normal and positive patterns had greater total social support than
      those who showed the negative pattern. The level of family support tended be
      higher among immigrants with the normal pattern, while support by friends tended
      to be greater among those with the positive pattern of change in distress.

PMID- 9242845
TI  - Communication disturbances in the natural speech of schizophrenic patients and
      non-schizophrenic parents of patients.
AB  - Subclinical communication disturbances in the relatives of schizophrenic patients
      appear to be heterogeneous in both form and origin. The Communication
      Disturbances Index (CDI) was applied to the natural speech of stable
      schizophrenic out patients, non-schizophrenic parents of patients, and control
      subjects. The parents of schizophrenic patients displayed more frequent overall
      instances of communication failure in their speech than the controls. The
      specific types of disturbance that were more frequent were structural lack of
      clarity, vague references and ambiguous word meanings. The parents did not differ
      significantly from the patients with regard to total CDI ratings. However,
      patients made more frequent missing-information references than parents, and
      parents made more frequent vague references than patients. High CDI scores in
      parents were associated with more severe lifetime core positive symptoms in their
      patient offspring.

PMID- 9242846
TI  - Suicidality in eating disorders: clinical and psychological correlates.
AB  - Although many authors have described eating disorders as often being associated
      with suicidal feelings and behavior, few studies to date have evaluated the
      prevalence and characteristics of suicidal behaviour in eating disordered
      patients. In the present study, in which a consecutive series of 495 out-patients
      was studied, 13% of the patients reported at least one suicide attempt and 29%
      reported current suicidal ideation; 26% of attempters reported multiple attempts.
      A history of suicide attempt was more prevalent among binge-eating/purging
      anorexics and among purging bulimics than in the other subgroups. In cases with
      anorexia nervosa, suicide attempters were older, had a longer illness duration,
      weighed less, had more often used drugs and/or alcohol and tended to be more
      obsessive than non-attempters. In cases with bulimia nervosa, attempters
      presented with more psychiatric symptoms and had more frequently been sexually
      abused.

PMID- 9242847
TI  - Hospital vs. outreach treatment of patients with mental retardation and
      psychiatric disorders: a controlled study.
AB  - The aim of this study was to investigate the effectiveness of specialized
      hospital treatment vs. outreach treatment of patients with mental retardation and
      serious mental illness. A total of 50 patients were randomly assigned to either
      the hospital treatment (n = 25) or the outreach treatment group (n = 25). The
      outcome measures included psychiatric symptoms, family burden, costs and hospital
      admissions. At most observation points (up to 28 weeks) and at all endpoints the
      two groups were equivalent with regard to psychiatric symptoms. The burden on
      carers did not increase significantly during the outreach treatment. Treatment
      costs were lower for the outreach treatment. Of the 25 patients who received
      outreach treatment, four had to be admitted to the specialized hospital.
      Aggressive behaviour, social competence and number of previous psychiatric
      hospitalizations were found to be predictors of treatment outcome. It is
      concluded that outreach treatment represents an effective and efficient
      alternative to hospital treatment for patients with mental retardation and
      psychiatric disorders.

PMID- 9242848
TI  - Lifetime and 12-month prevalence of DSM-III-R mental disorders among the homeless
      in Madrid: a European study using the CIDI.
AB  - The characteristics of homeless people in Europe are almost unknown. The aim of
      this study was to describe the lifetime and 12-month prevalence of DSM-III-R/CIDI
      mental disorders among the homeless population of Madrid. A total of 261 homeless
      subjects, sampled from different sites, participated in the study. In terms of
      DSM-III-R lifetime rates, 50% of the sample had substance-related disorders and
      35% had non-substance-related disorders. In total, 67% of the study subjects had
      some type of disorder. The lifetime prevalence of schizophrenia (4%) was lower
      than reported in most previous studies. Although the mental illness pattern is
      similar to that observed in studies using the same diagnostic methods, the
      results reported here show a lower prevalence of drug abuse and schizophrenic
      disorders. The reasons for these cultural differences and their implications for
      international public health research are discussed.

PMID- 9242849
TI  - The Dynamic Assessment Interview: testing the psychodynamic assessment variables.
AB  - The Dynamic Assessment Interview (DAI) is a semi-structured interview with
      anchored scales to rate patients; suitability for psychodynamic psychotherapy.
      The DAI was inspired by the Personality Assessment Interview developed by Selzer
      et al. in 1987 and it introduces from the beginning of the assessment interview
      an explicit focus on the patient's immediate interactions with the interviewer.
      Seven theoretical derived variables are assessed, namely psychological
      mindedness, capacity for self-observation, capacity for empathy, tolerance of
      frustration, motivation, response to confrontation, and ability to contain and
      work with affect. In addition, the patient's attractiveness as a psychotherapy
      patient and his or her assumed confidence in the forthcoming treatment are
      assessed. The patient's personality organization ad modum Kernberg is measured
      from a global assessment of the interview. The present paper describes the DAI
      and presents its psychometric properties. An acceptable level of inter-rater
      agreement was found for the theoretically derived variables and for the
      personality organization diagnosis, with intra-class correlations or kappa
      coefficients ranging from 0.68 to 0.80.

PMID- 9242850
TI  - The relationship between seasonal mood change and personality: more apparent than
      real?
AB  - A number of recent research reports have reported significant relationships
      between seasonal mood change (seasonality) and personality. However, some of the
      results are difficult to interpret because of inherent methodological problems,
      the most important of which is the use of samples drawn from the southern as
      opposed to the northern hemisphere, where the phenomenon of seasonality may be
      quite different. The present study examined the relationship between personality
      and seasonality in a sample from the northern hemisphere (minimum latitude = 49
      degrees N). A total of 297 adults drawn from the general population (112 male and
      185 female subjects) completed the Seasonal Pattern Assessment Questionnaire, and
      the results obtained confirmed most of the previously reported relationships and
      showed that these are reliable across (i) different hemispheres, (ii) different
      measures of personality and (iii) clinical and general population samples.
      However, the impact of the relationship seems to be more apparent than real, with
      personality accounting for just under 15% of the total variance.

PMID- 9242851
TI  - An investigation into the psychobiology of social phobia: personality domains and
      serotonergic function.
AB  - The aim of the present study was to explore a psychobiological perspective in the
      aetiology of social phobia. The emphasis was on serotonergic function and
      personality. A total of 20 social phobics according to ICD-10 DCR criteria were
      assessed with the Schedule for Clinical Assessment in Neuropsychiatry and the
      International Personality Disorder Examination. They were compared with an age
      matched normal population with regard to scores on the Fear of Negative
      Evaluation Scale, the Social Avoidance and Distress Scale, the Temperament and
      Character Inventory, and platelet 5HT2 receptor function. Other Axis-I disorders
      and cluster C personality disorders were frequently encountered. The social
      phobia group was characterized by high levels of harm avoidance, and low levels
      of novelty seeking, co-operativeness and self-directedness. Platelet 5HT2
      receptor density did not differentiate between the groups, but was associated
      with severity of social phobia. An integrated psychobiological model is
      presented.

PMID- 9242852
TI  - Co-administration of fluoxetine and sumatriptan: the Canadian experience.
AB  - Major depression and migraine are commonly comorbid. Therefore, there is
      considerable opportunity for serotonin reuptake inhibitors, which are commonly
      prescribed for the treatment of depression, to be used at the same time as
      sumatriptan, an anti-migraine treatment. As both of these drugs increase
      serotonin transmission, the potential for drug interaction is considerable.
      Adverse event reports were obtained from the post-marketing surveillance of
      fluoxetine in Canada. Of 22 adverse event reports obtained six showed varying
      degrees of evidence of a drug interaction between fluoxetine and sumatriptan,
      suggesting that this combination is not entirely free of side-effects and should
      be used with caution when indicated.

PMID- 9242853
TI  - Effects of object characteristics on female grasp patterns.
AB  - OBJECTIVE: This study determined which object characteristics had an effect on
      grasp when adult women took a drink from a cup. METHOD: Thirty women aged 20 to
      45 years (M = 27.6 years) were randomly assigned to a sequence for each of three
      experiments. The first experiment tested the grasp pattern used for cups of same
      height and weight but with different-sized handles. The second experiment tested
      the grasp pattern for cups of varied height but with same-sized handles and same
      weight. The third experiment tested the grasp pattern for cups of varied weight
      but with same-sized handles and same height. The grasp patterns were recorded by
      a videocamera placed across from the subjects. RESULTS: The number of fingers
      placed through the handle was found to be significantly greater for the cup with
      a larger handle than for the cups with the smaller handles when cup size and
      weight were held constant, chi(2)(2) = 49.8, p < .001. No significant difference
      was found in the number of supporting fingers for varying cup heights or weights.
      CONCLUSION: The results support other research that has stated that handle size
      accounted for the change in grasp pattern. Because motor performance is affected
      by the object characteristics as well as personal abilities, adaptation of
      characteristics, such as handle size, for persons with limited hand use may
      provide an environment that evokes more optimal performance.

PMID- 9242854
TI  - Factor analysis on the Sensory Profile from a national sample of children without
      disabilities.
AB  - OBJECTIVE: The purpose of this study was to identify relationships in the 125
      items of the revised Sensory Profile, a tool designed to assess children's
      responses to commonly occurring sensory events. METHOD: Parents of 1,115 children
      ages 3 to 10 years and without disabilities completed the Sensory Profile. The
      parents reported the percentage of time their children engaged in each of the 125
      behaviors listed on the profile. RESULTS: Factor analysis revealed nine discreet
      factors that indicate sensory modulation and responsiveness: sensory seeking,
      emotionally reactive, low endurance/tone, oral sensory sensitivity,
      inattention/distractibility, poor registration, sensory sensitivity, sedentary,
      and fine motor/perceptual. CONCLUSIONS: In addition to the traditional method of
      organizing sensory history information by sensory system, we may need to consider
      a person's thresholds to sensory events as well as his or her responsiveness to
      sensation. Because the Sensory Profile factors in these children without
      disabilities are similar to patterns observed in children with various
      disabilities, it may be that some sensory processing problems are related to
      intensity or duration of behaviors as they begin to interfere with functional
      performance in daily life.

PMID- 9242855
TI  - Sensory processing in the postinstitutionalized child.
AB  - OBJECTIVE: The purpose of this study was to examine whether children adopted from
      Romanian orphanages have difficulty with sensory processing and related
      behaviors. METHOD: Seventy-three children adopted from Romanian orphanages were
      compared with 72 peers who were typically developing. The subjects' ages ranged
      from 3 to 6 years. The parent-report Developmental and Sensory Processing
      Questionnaire was used to assess sensory processing and related behaviors. The
      tool consists of questions in six sensory processing domains and five related
      behavioral domains. RESULTS: Multiple t tests indicated that the subjects adopted
      from Romanian orphanages demonstrated significantly greater problems than those
      in the control group on five of the six sensory processing domains: touch,
      movement-avoids, movement-seeks, vision, and audition. Additionally, the Romanian
      subjects exhibited significantly greater problems than the control subjects on
      four of the five behavioral domains: activity level, feeding, organization, and
      social-emotional. CONCLUSIONS: These findings substantiate clinical observations
      and parent reports of sensory processing deficits in children adopted from
      Romanian orphanages and highlight the critical importance of the environment for
      sensory integration. The findings also enhance our understanding of how children
      who were previously institutionalized respond to the human and physical
      environment.

PMID- 9242856
TI  - The effect of added-purpose and meaningful occupation on motor learning.
AB  - OBJECTIVE: Numerous studies in the occupational therapy literature have
      investigated the effects of added-purpose (multidimensional, goal-oriented)
      occupation on performance. Motor learning research has demonstrated that factors
      that enhance performance measures do not necessarily enhance motor learning. This
      study examined the effects of both added-purpose and meaningful occupation on
      motor learning. METHOD: Twenty subjects (university students) were randomly
      assigned to either an added-purpose or rote exercise condition. After a skill
      acquisition phase, retention and transfer scores were obtained, and subjects were
      asked to rate the meaningfulness of the occupation on a visual analog scale.
      RESULTS: A two-way analysis of variance indicated that only the added-purpose
      occupation resulted in significantly greater motor learning. Additionally, the
      added-purpose scores were not influenced by the level of meaning assigned to the
      occupation. CONCLUSION: This study is the first to demonstrate how added-purpose
      can enhance a more permanent aspect of performance: motor learning. Further
      research is necessary to determine whether occupations that both are meaningful
      and have added-purpose are the most effective in enhancing motor learning.

PMID- 9242857
TI  - Comparison of the test-retest reliability of the Work Box using three
      administrative methods.
AB  - OBJECTIVE: The purpose of this study was to compare the test-retest reliability
      of three administrative methods of the Work Box: (a) the original instructions,
      (b) a revised version of the original instructions, and (c) another revised
      version that was based on suggestions made by authors of the first two versions
      of the instructions. METHOD: Sixty subjects without disabilities were randomly
      grouped so that 20 subjects were tested per administrative method. The assessment
      was administered to each subject on two occasions, with a 7-day to 14-day period
      between tests. Scores were recorded as time in seconds, and intraclass
      correlation coefficients (ICCs) were used to calculate the reliability. RESULTS:
      The ICCs for assembly, disassembly, and total scores were .589, .604, and .654,
      respectively, for the original instructions; .424, .572, and .545 for the revised
      instructions; and .781, .579, .717 for the second revised instructions.
      Reliability was found to be higher for men than for women and for subjects who
      claimed to have more rather than less experience in similar manual dexterity
      tasks. CONCLUSIONS: On the basis of the reliability of each administrative method
      and comments made by subjects about their understanding of the instructions, the
      second revised version of the instructions is recommended as the standard method.
      The results also indicate that the assessment is most appropriate for a
      population of men with manual dexterity experience. With further standardization,
      the Work Box could be a valuable assessment tool for therapists working in
      industrial rehabilitation settings.

PMID- 9242858
TI  - Occupational adaptation intervention with patients with cerebrovascular accident:
      a clinical study.
AB  - OBJECTIVE: The purpose of this study was to examine the use of the Occupational
      Adaptation frame of reference in the evaluation and treatment of patients with
      cerebrovascular accident (CVA). METHOD: Outcomes of functional independence and
      discharge environment were measured through a quasi-experimental design. Twenty
      five former patients served as the control subjects, and 25 patients admitted
      after the programmatic implementation of Occupational Adaptation served as the
      treatment subjects. RESULTS: Data analyses indicated that the Occupational
      Adaptation subjects achieved higher levels of functional independence and were
      discharged to less restrictive environments compared with the control subjects.
      CONCLUSION: Use of intervention guided by the Occupational Adaptation frame of
      reference was associated with improved functional independence and discharge to
      less-restricted environments for this group of patients with CVA.

PMID- 9242859
TI  - A comparison of the performance of children with and without autism on the
      Sensory Profile.
AB  - OBJECTIVE: The purpose of this study was to determine whether the Sensory Profile
      discriminates between children with and without autism and which items on the
      profile best discriminate between these groups. METHOD: Parents of 32 children
      with autism aged 3 to 13 years and of 64 children without autism aged 3 to 10
      years completed the Sensory Profile. A descriptive analysis of the data set of
      children with autism identified the distribution of responses on each item. A
      multivariate analysis of covariance (MANCOVA) of each category of the Sensory
      Profile identified possible differences among subjects without autism, with mild
      or moderate autism, and with severe autism. Follow-up univariate analyses were
      conducted for any category that yielded a significant result on the MANCOVA:
      RESULTS: Eight-four of 99 items (85%) on the Sensory Profile differentiated the
      sensory processing skills of subjects with autism from those without autism.
      There were no group differences between subjects with mild or moderate autism and
      subjects with severe autism. CONCLUSION: The Sensory Profile can provide
      information about the sensory processing skills of children with autism to assist
      occupational therapists in assessing and planning intervention for these
      children.

PMID- 9242860
TI  - The use of low-load prolonged stretch devices in rehabilitation programs in the
      Pacific northwest.
AB  - OBJECTIVE: This retrospective study examined the use of low-load prolonged
      stretch (LLPS) orthoses for contracture management. METHOD: The records of 17
      patients from skilled nursing facilities, hand clinics, and hospitals were
      reviewed. There was a total of 18 contractures (2 wrist, 12 elbow, 4 knee)
      secondary to neurological and orthopedic pathologies. Chart review focused on
      patient demographic information, range of motion (ROM) and functional outcomes,
      and wear schedules. RESULTS: The use of LLPS orthoses significantly increased ROM
      for the whole sample, which in turn significantly improved the subjects'
      functional outcomes. When the sample was divided into two pathology groups to
      compare a predominately geriatric population with neurological pathologies to a
      somewhat younger population with a history of musculoskeletal pathology, both
      groups showed a significant gain in ROM with the use of the LLPS orthoses.
      CONCLUSION: Use of LLPS orthoses for contractive management can mediate the
      losses in ROM and function that occur with joint contractures.

PMID- 9242861
TI  - In-hand manipulation in young children: rotation of an object in the fingers.
AB  - OBJECTIVE: The purpose of this study was to look at the development of two in
      hand skills of rotation. Three questions were asked: (a) Do boys' and girls'
      performance differ significantly? (b) Does performance improve with age? and (c)
      Can periods of rapid improvement with age be seen on the tasks presented? METHOD:
      The in-hand manipulation skill of rotation was measured in 154 right-handed
      children between the ages of 3-0 years and 6-11 years as well as in 13 adults.
      The participants were videotaped as they either turned over small pegs in a
      pegboard or rotated a peg in their fingertips. The number of pegs dropped when
      turning and placing them back in the board, the number of times a peg could be
      rotated in the fingertips, the time it took to complete each task, and the
      methods participate used to accomplish the two tasks were recorded from the
      videotapes. RESULTS: The results indicated no differences between the performance
      of boys and girls on any of the variables studied, but performance did change
      with age, and periods of rapid change were identified. Further, when compared on
      methods used, the children did not achieve the same speed or consistency as the
      adult participants. CONCLUSION: The development of in-hand manipulation skills of
      rotation involves improvement in the dimension of speed, method, and consistency.
      Observation of these skills in a child can add to a therapist's understanding of
      the child's fine motor abilities. The variability in children's performance needs
      to be considered in both evaluation and treatment planning.

PMID- 9242862
TI  - Educational participation of children with spinal cord injury.
AB  - OBJECTIVE: The purpose of this study was to examine educational participation and
      accommodations for children with spinal cord injury (SCI) or disease in primary,
      secondary, and postsecondary educational settings. METHOD: Written surveys were
      developed for students with SCI and their teachers. Fifty-three participants had
      SCI onset before age 18 years, were at least 4 years old and enrolled in a school
      program, and had residual motor disability without cognitive-behavioral
      impairments. RESULTS: Nearly all participants were enrolled full time in regular
      education classrooms. Seventy-five percent of primary-level participants and 32%
      of secondary-level participants were qualified for special education and related
      services, receiving teacher aide assistance as well as occupational and physical
      therapy services. Most participants were graduating from high school and pursing
      postsecondary education. Classroom performance and grades were reported as
      average or above average, but curriculum modifications were commonly made, and
      many participants required human assistance and assistive technology in
      functional and classroom tasks. Access barriers were often reported by
      participants using wheelchairs, and those using augmentative writing aids were
      not fluent with these devices. CONCLUSION: Accommodations in schools for students
      with SCI appear to support completion and advancement to higher levels of
      education, but these accommodations appear to be geared toward participation
      rather than levels of performance and productivity that may be realistic for work
      and other community settings.

PMID- 9242863
TI  - Comparison of the performance of younger and older adults on three versions of a
      puzzle reproduction task.
AB  - OBJECTIVES: Because constructional ability is a crucial perceptual-motor skill
      that relates to daily functioning, it should be accurately assessed in clients
      with neurological dysfunction. This study examined three versions of the Puzzle
      Reproduction task (a constructional ability task) of the Loewenstein Occupational
      Therapy Cognitive Assessment (LOTCA) in order to determine whether a reduced
      detail version of the task would be easier (i.e., require less time to complete)
      than the original version and whether a subplacement version would be more
      difficult to perform (i.e., require more time to complete) than the original
      version. In addition, the study examined whether older adult subjects would
      perform more slowly than younger adult subjects. METHODS: Seventy-two right
      handed adults with no disabilities were divided into two age groups: 18 to 30
      years old (n = 36) and 58 to 70 years old (n = 36). Each subject was tested on
      one of three versions of the LOTCA Puzzle Reproduction task (i.e., original
      subplacement, simplified). RESULTS: For the older subjects, the simplified
      version of the task required significantly less time than the original version,
      although there was not a significant time difference between the original and
      subplacement versions. For the younger subjects, the subplacement versions.
      required significantly more time than the original version, but there was no
      significant time difference between the original and simplified versions. Results
      also indicated that older subjects took significantly longer to perform all three
      versions of the task than did the younger subjects. CONCLUSION: The findings
      support the use of the simplified version of the LOTCA Puzzle Reproduction task
      with older adults or with persons with major cognitive-perceptual difficulties.
      Further studies of the level of difficulty of the subplacement version are needed
      to examine whether this version is more sensitive to constructional deficits in a
      sample of person with neurological impairments because even mild constructional
      deficits have been shown to relate to disabilities in daily functioning.

PMID- 9242864
TI  - Job analysis in occupational therapy: stepping into the complex world of business
      and industry.
AB  - Job analysis is used in a variety of fields to identify the nature of work
      performed. Occupational therapists use job analysis is a basis for evaluating
      injured workers, planning rehabilitative programs, structuring preemployment
      screening protocols, developing transitional work plans, and conducting
      environmental modification and risk management programs. There is little evidence
      in the literature of a theoretical basis or practical framework for job analysis
      in occupational therapy, although the theory that underlies occupational therapy
      provides a general foundation. Current job analysis methods appear inadequate for
      the wide range of practice applications and for responding to the changing nature
      investigation of methods derived from occupational therapy and other disciplines,
      development of documentation approaches suited to a variety of job types, and
      attention to validity and reliability o f results.

PMID- 9242865
TI  - The planning process in occupational therapy: perceptions of adult rehabilitation
      patients.
AB  - OBJECTIVES: The purpose of this study was to learn about (a) adult physical
      rehabilitation patients' perceptions of their involvement in the treatment
      planning process (goal setting, treatment planning, outcome evaluation), (b)
      their valuation of occupational therapy, and (c) how they would describe their
      interpersonal relationships with their occupational therapists. METHOD: Fifteen
      subjects who had received occupational therapy were interviewed. The transcripts
      were independently and jointly reviewed by the authors to answer five research
      questions. RESULTS: Most of the subjects indicated that they had been involved in
      occupational therapy goal setting; treatment planning; and outcome evaluation,
      albeit this indication was weak. They also valued the occupational therapy
      services they received. Eight described positive interpersonal interactions with
      their therapists, and seven provided no information. CONCLUSION: Patients
      receiving occupational therapy services are involved in goal setting, treatment
      planning, and outcome evaluations; however, their involvement varies and can be
      difficult for them to identify and describe. Because of increasing societal
      emphasis on patient rights and participation (e.g., consumerism, health
      professions standards, health care accreditation criteria, health care
      legislation) and the likelihood that health care funding will be used for
      services linked to patient goals, occupational therapy practitioners could become
      more overt and systematic in involving patients in the planning process.
      Increasing patient involvement in planning may result in more individualized
      treatment and more effective use of health care dollars.

PMID- 9242866
TI  - Academic integration of occupational therapy faculty: a survey.
AB  - OBJECTIVE: This descriptive study explored the reasons for occupational therapy
      faculty members selecting academia as a career, their use of faculty development
      practices, and the relationship of organizational culture to collegial support.
      METHOD: Full-time faculty members (n = 191) from accredited occupational therapy
      professional programs in the United States completed a questionnaire about their
      early years in academia. RESULTS: Respondents indicated that their primary reason
      for selecting academia as a career was their love of teaching. The most helpful
      faculty development practice was frequent sharing of ideas with peer faculty
      members. CONCLUSIONS: The findings support the following recommendations for
      program administrators and experienced faculty members to assist new faculty
      members in adapting to academia: (a) support and develop new avenues for sharing
      ideas in formal and informal settings; (b) develop mentoring programs, with new
      faculty members observing experienced teachers and receiving feedback and
      assistance for their own teaching; (c) encourage attendance at instructional
      seminars; (d) provide resource materials and texts on improving teaching and
      research skills; (e) allow time for research; and (f) encourage coauthoring of
      publications.

PMID- 9242867
TI  - Student perceptions of a problem-based learning course.
AB  - Within occupational therapy education, there has been increased attention to
      curricula and courses that emphasize problem solving, clinical reasoning, and
      synthesis of information across traditional discipline-specific boundaries. This
      article describes the development, implementation, and outcomes of a problem
      based learning course entitled Selected Cases in Occupational Therapy. The course
      was designed to help students to integrate the various elements of a specific
      occupational therapy curriculum and to enhance their abilities to respond to an
      ever-changing health care environment. An evaluation of the course by the first
      11 students who completed it revealed both strengths and weaknesses. Students
      responded that the course enhanced their professional behavior, including
      interpersonal communication skills, team work, and follow-through with
      professional responsibilities; helped them to integrate the various elements of
      the total occupational therapy academic program; enhanced their clinical
      reasoning skills by providing a structure for thinking through clinical issues;
      and provided personal gain or benefit (i.e., students perceived the course to be
      a valuable, realistic, and motivating experience). The students also identified
      several specific course elements that contributed to its integrating function,
      including content, class session format, and students' role. Identified course
      weaknesses included the methods of evaluating student performance and the format
      and content of specific cases.

PMID- 9242868
TI  - A model of the nature of family-therapist relationships: implications for
      education.
AB  - OBJECTIVES: The family play an important role in rehabilitation of persons with
      chronic disabilities and in supporting their reintegration into the community. To
      be prepared for family-centered intervention, educators need to frame the content
      that occupational therapy students must master. The purpose of this study was to
      develop a hierarchy of occupational therapists' attitudes about the family's
      involvement in services for a family member with special needs. METHOD:
      Participants were 302 occupational therapists who reported some contact with
      families of clients. Through an open-ended question, participants were asked to
      indicate the most important outcome of their interactions with their clients'
      families. RESULTS: Analysis of participant responses led to the development of a
      seven-level hierarchy of family-therapist interactions. The levels are based on
      the participants' views of the outcome of family involvement as suggested by
      their attitudes about a family's role and abilities. Knowledge and skills needed
      to work at different levels of the hierarchy are identified. CONCLUSION:
      Recommendations for preparation of entry-level practitioners to work at all
      levels of the model are discussed.

PMID- 9242869
TI  - Biofeedback for writer's cramp.

PMID- 9242870
TI  - Latex sensitivity in children with spina bifida: implications for occupational
      therapy practitioners.

PMID- 9242871
TI  - Should we trade person-centered service for a consumer-based model?

PMID- 9242872
TI  - Invasive aspergillosis of the paranasal sinuses and orbit: can you save the eye?

PMID- 9242873
TI  - Cervical spine injury complicating facial trauma: incidence and management.
AB  - PURPOSE: To review the impact of concomitant cervical spine injury on the
      management of facial fractures in a tertiary care institution via a retrospective
      chart review. PATIENTS AND METHODS: Within the past 10 years, 1,750 consecutive
      patients presented to our institution with facial fractures. Thirty-two had
      concomitant cervical spine injury. Five were transferred or died before
      treatment. The remaining 27 charts were reviewed in detail. RESULTS: The
      incidence of cervical spine injury among patients with facial fractures in our
      study was 1.8%. There were no treatment delays attributed to these injuries. Of
      note was the inaccuracy of lateral cervical spine films in 9 of 27 cases (33%).
      CONCLUSION: Although uncommon, cervical spine injury must be thoroughly ruled out
      before evaluation and management of facial trauma. Concomitant cervical spine
      injury should not delay appropriate and timely treatment of facial fractures
      because adequate means of intraoperative stabilization are readily available.

PMID- 9242874
TI  - Interleukin-3 interleukin-5, and granulocyte-macrophage colony-stimulating factor
      expression in nasal polyps.
AB  - PURPOSE: Nasal polyps (NP) are grape-like clusters of chronically inflamed
      tissue. Little is known about the underlying cells and cytokines involved in
      nasal polyposis. For the present study, we hypothesize that elevated tissue
      levels of interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage
      colony-stimulation factor (GM-CSF) contribute to eosinophil recruitment and
      activation in NP. MATERIALS AND METHODS: To begin to test this hypothesis, we
      evaluated IL-3, IL-5, and GM-CSF levels and distributions in nasal polyp
      specimens obtained intraoperatively from 13 patients and two normal controls. For
      these studies, nasal polyp levels were determined by enzyme-linked immunosorbent
      assay (ELISA), and IL-3, IL-5, and GM-CSF distribution was determined by
      immunohistochemistry. RESULTS: Immunohistochemical staining of the NP indicated
      that in all 13 patient samples, IL-3, IL-5, and GM-CSF were associated with
      infiltrating cells, primarily eosinophils, in the NP. Quantitation of IL-3, IL-5,
      and GM-CSF in NP tissue homogenates indicated that IL-3, IL-5, and GM-CSF levels
      were evaluated in the NP tissues when compared with control tissues.
      Additionally, elevation of individual cytokines correlated with previous
      polypectomy (IL-3), steroid use (IL-3, IL-5, and GM-CSF), asthma (IL-5), and age
      (GM-CSF). CONCLUSION: These data support our hypothesis that IL-3, IL-5, and GM
      CSF are likely to play a key role in eosinophil recruitment/activation and NP
      formation and support recently advanced theories that cytokines play a key role
      in the pathogenesis of this disease.

PMID- 9242876
TI  - Color duplex echography in head and neck cancer.
AB  - PURPOSE: The aim of the present study was to demonstrate the rating of low-flow
      color duplex echography in the staging of head and neck cancer. PATIENTS AND
      METHODS: Fifty-two patients with squamous cell carcinoma of the oral cavity, the
      oropharynx, and hypopharynx were examined. A Siemens Q 2000 duplex scan with 7.5
      MHz-linear array and wedge (Siemens Medizintechnik, Siemens Medical Systems,
      Erlangen, Germany) was used. Gray scale imaging as well as color duplex scan with
      Doppler spectrum measurement were performed for each patient. RESULTS: Only 5 of
      52 primary tumors could not be detected using echography (sensitivity: 90%).
      Tumor size of one carcinoma, a recurrent tumor of the laryngeal sinus, was
      overestimated (predictive value: 96%). The carcinomas and their metastases were
      poorly vascularized. Only 10 of 52 primary tumors showed central vascularization.
      The mean systolic flow rate in these vessels was 40 cm/s. In 17 patients, imaging
      of peripheral tumor vessels improved estimation of tumor borders. Imaging of
      irregular central tumor vessels in metastatic lymphatic nodes yielded important
      information for N staging. CONCLUSION: Low-flow color duplex echography is a new
      high resolution, noninvasive imaging technique that offers important additional
      information for preoperative head and neck tumor staging. Thus, it should be
      recommended for routine application in ENT-oncology.

PMID- 9242875
TI  - Endonasal microendoscopic pansinusoperation in chronic sinusitis. II. Results and
      complications.
AB  - PURPOSE: We evaluated the long-term results and complications of endonasal
      pansinusoperation in chronic polypoid sinusitis. PATIENTS AND METHODS: In a
      retrospective study, 170 patients were followed-up for 20 months to 10 years
      after bilateral endonasal microendoscopic pansinus surgery or ethmoidectomy. The
      follow-up consisted of a standardized questionnaire and clinical examination with
      the flexible endoscope. RESULTS: We found that 85.6% of the ethmoid cell systems,
      69.4% of maxillary sinuses, and 37.5% of frontal sinuses could be visualized
      endoscopically. The ethmoid mucosa was normal in 56% and thickened in 19%.
      Recurrent polyps were found in 25%. The evaluation--as per the graduation of
      results defined by us as a combination of examination findings and subjective
      assessment of the operative result--resulted in an operative success of 92%. Two
      studies dealing with the frequency of complications showed injury to the dura in
      2.3% to 2.55% and periorbital injury without permanent sequelae in 1.4% to 3.4%.
      Because of two cases of bleeding from the internal carotid artery, the problems
      of vascular complications in particular will be thoroughly discussed. CONCLUSION:
      More than 90% of patients with chronic polypoid sinusitis gain long-term
      satisfying results after endonasal ethmoidectomy with microscope and endoscope.
      For minimizing the risk of injury of the optic nerve or the internal carotid
      artery preoperative, computed tomography is necessary. A special training program
      is recommended.

PMID- 9242877
TI  - Retropharyngeal abscess: pitfalls of plain films and computed tomography.

PMID- 9242878
TI  - Bilateral sinonasal papillomas in aplastic maxillary sinuses.

PMID- 9242880
TI  - Foreign body in the trachea: fragmentation and migration.

PMID- 9242879
TI  - Malignant familial glomus jugulare and contralateral carotid body tumor.

PMID- 9242881
TI  - Transantral evacuation of an orbital abscess following a molar tooth extraction.

PMID- 9242882
TI  - Renal cell carcinoma presenting as a masseteric space mass.

PMID- 9242883
TI  - Treatment of recurrent respiratory papillomatosis with indole-3-carbinol.

PMID- 9242884
TI  - Platelets and inflammation.
AB  - Besides their functions in the haemostatic process and in thrombus formation
      after an endothelial injury, blood platelets also take part in the processes of
      inflammation and tissue repair that follows. For this purpose, they closely
      collaborate with all types of leukocytes. Activated platelets secret chemotactic
      substances, they facilitate the binding of leukocytes to the endothelium and
      their subsequent extravasation, and they may influence the inflammatory responses
      of leukocytes in both stimulating and inhibiting ways. However, platelets
      themselves also contain an array of potent proinflammatory substances, and
      therefore they are regarded as mediator and effector cells in inflammation. Their
      capability to interact with bacteria, parasites, and other foreign materials is
      possibly a phylogenetic vestige and may explain the existence of IgE-dependent
      killing mechanisms of platelets. On the other hand, the connection between IgE
      and platelets, besides the platelet-induced eosinophil infiltration, offers a
      functional basis for the involvement of platelets in allergic processes,
      particular in the skin and the airways.

PMID- 9242885
TI  - Developmental expression of the CD15-epitope in the brainstem and spinal cord of
      the mouse.
AB  - The expression of the 3-fucosyl-N-acetyl-lactosamine (FAL, CD15, Le(x)) epitope
      has been examined immunohistochemically in paraffin sections of the brainstem of
      the mouse. The initial appearance of labelling was at embryonic day (E)11, when
      immunoreactivity of radial glial fibres was noted in the medulla, pons and dorsal
      isthmus, while the spinal cord was immunoreactive from E12. Labelling remained
      faint until E14, when a distinctive radial pattern appeared in the medulla, pons
      and spinal cord. Immunoreactivity at E14 in both the spinal cord and medulla was
      strongest in a band in line with the sulcus limitans, passing ventrolaterally
      through the nucleus of the solitary tract in the case of the medulla. In both the
      spinal cord and the medulla, CD15 immunoreactivity divided the brainstem into
      radially arranged compartments, with an immunonegative paramedian region,
      strongly labelled ventrolateral segments, and moderately labelled lateral
      regions. Labelling of midline radial fibres was also apparent in the ventral
      mesencephalon at E14. After E18, labelling appeared in the paramedian region of
      the medulla, in particular around the inferior olivary nucleus, and gradually
      adopted a tufted appearance throughout the brainstem. Several regions of the
      developing brainstem showed specific labelling during fetal life. Distinct
      labelling of the developing red nucleus was visible from E15 to the time of
      birth, while some longitudinal bands of labelling were noted in the deeper layers
      of the superior colliculus from E17 until postnatal day (P)2. The adult pattern
      of immunolabelling was achieved by the end of the second postnatal week. The
      striking concentration of CD15 along the sulcus limitans of both the spinal cord
      and brainstem may serve to demarcate and separate dorsal (sensory) and ventral
      (motor) columns in a similar fashion to Pax gene expression. The precise timing
      of transient CD15 expression in the developing inferior olive and red nucleus is
      suggestive of a role for this epitope in developmental events of those
      structures.

PMID- 9242886
TI  - Effects of cholinergic depletion on glutamic acid decarboxylase immunoreactivity
      in the somatosensory cortex of rats.
AB  - The purpose of these experiments was to determine the effects of cholinergic
      depletion on the morphology and staining density of barrels formed by glutamic
      acid decarboxylase-positive neuropil in the posteromedial barrel subfield of the
      somatosensory cortex. The density and distribution of glutamic acid decarboxylase
      immunoreactive neuropil were examined after highly selective lesions of
      cholinergic neurons in the nucleus basalis of Meynert with an immunotoxin, IgG
      192-saporin. Glutamic acid decarboxylase immunoreactivity was also examined in
      animals subjected to a whisker-pairing experience and lesion of acetylcholine
      inputs from the nucleus basalis of Meynert. Seven to 9 weeks after
      intraventricular injection of the immunotoxin, animals were perfused with a zinc
      aldehyde fixative and glutamic acid decarboxylase immunoreactivity was examined
      in 30-micron tangential sections. Cholinergic depletion caused reduced glutamic
      acid decarboxylase immunoreactivity in selective regions of the posteromedial
      barrel subfield. The density of neuropil and cell bodies immunoreactive for
      glutamic acid decarboxylase was significantly reduced in septa and perimeters of
      barrel walls. The length, width, and area of barrels were reduced 10-20% in
      cholinergic-depleted animals compared with controls. The density of glutamic acid
      decarboxylase immunoreactivity in the hollow of barrels was not affected by this
      treatment. Whisker pairing did not significantly change the density of glutamic
      acid decarboxylase immunoreactivity in barrels. These observations are discussed
      in regard to how long-term cholinergic depletion affects the function of
      different fiber systems in the posteromedial barrel subfield cortex and how some
      sensory functions may be comprised.

PMID- 9242887
TI  - Mullerian duct regression in a marsupial, the tammar wallaby.
AB  - Mullerian duct regression is first apparent in male pouch young of the tammar
      wallaby (Macropus eugenii) 6-7 days after birth and, as in eutherian mammals, is
      characterised by a condensation of the periductal mesenchyme into a whorl around
      the ductal epithelial cells. A decrease in the density of the extracellular
      matrix was observed in the region of the whorl. In contrast to eutherian mammals
      no changes were observed in the mean outer diameter of the Mullerian duct during
      the early stages of regression. The time at which these mesenchymal changes occur
      corresponds to the period of Mullerian inhibiting substance secretion in the
      postnatal tammar testis.

PMID- 9242888
TI  - Distribution of glial fibrillary acidic protein-immunopositive structures in the
      developing brain of the turtle Mauremys leprosa.
AB  - This study is a continuation of the description of the glial fibrillary acidic
      protein (GFAP)-immunopositive structures in the adult turtle brain (Kalman et al.
      1994) and presents a comprehensive description of the development of these
      structures from the 20th embryonic day (E20) to the adult age. GFAP
      immunopositive elements were first detected at E28 and by E34 the GFAP
      immunopositivity was apparent throughout the brain, except the cerebellum. The
      appearance of GFAP seemed to be related to the end of cell migration and the
      formation of the thickened parts of the brain wall, such as the dorsal
      ventricular ridge. After hatching the pattern of the GFAP-immunopositivity
      differed from that in the adult only in minute details, except for the brain
      tracts in which GFAP-pattern was still changing due to myelination, and the
      molecular layer of the cerebellum in which a transverse fiber system appeared.
      The GFAP-positive elements belonged originally to the ependymoglia, but later the
      distortion due to the morphogenetic processes of branching and division changed
      the pattern almost beyond recognition. In some cases cell bodies--ependymal and
      non-ependymal--appeared to be GFAP-positive, but no astrocytes (i.e. stellate
      cells) were detected. The results are discussed in the light of previous
      observations on developing mammalian, avian and lizard brains.

PMID- 9242889
TI  - Development of the neonatal rabbit retina in organ culture. 1. Comparison with
      histogenesis in vivo, and the effect of a gliotoxin (alpha-aminoadipic acid).
AB  - Organ cultures from neonatal rabbit retinae grew well over periods of up to 2
      weeks in vitro. Proliferation in vitro declined in parallel with the decline seen
      in vivo, although the rate of proliferation in the explants was slightly reduced.
      The proliferation of progenitor cells in vitro produced the same cell types
      produced postnatally in vivo. Postnatally generated cell clones, labeled by means
      of a retroviral vector, consisted mainly of rods and Muller cells. The layers of
      the retinae developed as in vivo; an outer plexiform layer occurred after the
      first 2 days in vitro. Ultrastructurally, ribbon synapses (outer and inner
      plexiform layer) and conventional synapses (inner plexiform layer) were observed.
      The photoreceptor cells grew well-developed inner segments and cilia but no
      mature outer segments. The cultured retinae contained a well-developed, regular
      lattice of Muller cells expressing vimentin as in vivo. The neuron-to-Muller cell
      ratios were essentially the same as in vivo, viz. about 15 to 16 neurons, among
      them about 10 to 11 (rod) photoreceptor cells per Muller cell. When the glia cell
      specific toxin alpha-aminoadipic acid (alpha AAA) was applied, the pattern of
      vimentin-positive Muller cells became irregular, or even locally missing. In such
      cases, the tissue became disorganized as indicated by a local disappearance of
      the regular layering, and development of many rosettes. It is concluded that an
      intact lattice of Muller cells is necessary for the migration of young neurons,
      and for correct formation of retinal layers.

PMID- 9242890
TI  - Temporal and spatial patterns of phosphotyrosine immunolocalization during
      cardiac myofibrillogenesis of the chicken embryo.
AB  - To investigate the possible role of phosphorylation of protein tyrosine during
      myofibrillogenesis (6- to 13-somite stages) of the chicken embryonic heart tube,
      immunolocalization of phosphotyrosine (P-Tyr) and the relationship between P-Tyr
      and developing myofibrils were studied by means of confocal scanning laser
      microscopy and immuno-electron microscopy. The staining pattern of P-Tyr varied
      in different sites of myocytes at different stages of embryonic development: At
      the cell-cell boundaries, P-Tyr was localized at the adhesion belt of outer
      myocardial layer cells (6- to 13-somite stages), non-junctional cell-cell
      contacts (6- to 13-somite stages) and early intercalated disks of both the outer
      and inner myocardial layer cells (8- to 13-somite stages). At the cell
      extracellular matrix boundaries of inner layer cells, the first stages of
      myofibril formation appeared as serially aligned areas of P-Tyr localization
      closely associated with circumferentially aligned thick actin bundles (8- to 9
      somite stages). This P-Tyr immunostaining decreased when the thick actin bundles
      developed into mature striated myofibrils at the 10- to 13-somite stages. These
      findings suggest that the phosphorylation of protein tyrosine residues is
      primarily concentrated at the modulating cell-cell and cell-matrix adhesion sites
      of developing myocytes and myofibrils.

PMID- 9242891
TI  - In memoriam George Winokur, M.D. February 10, 1925-October 12, 1996.

PMID- 9242892
TI  - Antipsychotic drug doses and adjunctive drugs in the outpatient treatment of
      schizophrenia.
AB  - This study investigated factors associated with the dose of antipsychotic
      medication prescribed at a schizophrenia unit outpatient clinic. The
      antipsychotic drug dose prescribed for 364 patients was converted to
      chlorpromazine equivalents (CPE) per day and concurrent prescriptions of lithium,
      carbamazepine, benzodiazepines, and antiparkinsonian drugs were recorded. We
      found that patients prescribed lithium, carbamazepine, and/or benzodiazepines as
      adjunctive drugs were receiving significantly higher doses of antipsychotic
      medication (p < 0.05). Patients prescribed both depot and oral neuroleptic drugs
      concurrently were receiving higher CPE-equivalent doses than those receiving
      either drug type alone (p < 0.05), and high-potency oral drugs were prescribed in
      higher CPE-equivalent doses than low-potency oral drugs (p < 0.05). Patients
      prescribed antiparkinsonian drugs were not receiving significantly higher CPE
      equivalent doses of antipsychotic medication than patients not prescribed these
      drugs. There were no significant gender differences in the use of adjunctive
      drugs or in CPE-equivalent antipsychotic drug dose. Further research is needed to
      determine whether these findings are related to factors such as illness severity
      or to physician's prescribing practices.

PMID- 9242893
TI  - High-resolution brain SPECT imaging in ADHD.
AB  - Children and adolescents with ADHD were evaluated with high-resolution brain
      SPECT imaging to determine if there were similarities between reported PET and
      QEEG findings. Fifty-four children and adolescents with ADHD by DSM-III-R and
      Conners Rating Scale criteria were evaluated. A non-ADHD control group was also
      studied with SPECT. Two brain SPECT studies were done on each group, a resting
      study and an intellectual stress study done while participants were doing a
      concentration task. Sixty-fiver percent of the ADHD group revealed decreased
      perfusion in the prefrontal cortex with intellectual stress, compared to only 5%
      of the control group. These are findings consistent with PET and QEEG findings.
      Of the ADHD group who did not show decreased perfusion, two-thirds had markedly
      decreased activity in the prefrontal cortices at rest.

PMID- 9242894
TI  - Pergolide to augment the effectiveness of antidepressants: clinical experience
      and a small double-blind study.
AB  - To attempt to confirm a prior report that pergolide can augment the efficacy of
      antidepressants in refractory patients, pergolide was administered to 12 patients
      receiving antidepressants. Eight patients were involved in a placebo-controlled
      evaluation of pergolide; the others were prescribed pergolide clinically. Results
      showed no evidence of benefit, so the double-blind study has been discontinued.

PMID- 9242895
TI  - Diagnosis, treatment, and six-month outcome status in first-admission psychosis.
AB  - Six-month outcome status was examined in 202 first-admission inpatients with DSM
      III-R schizophrenia spectrum (N = 96), psychotic bipolar disorder (N = 64), and
      psychotic depression (N = 42) drawn from 10 facilities in Suffolk County, New
      York. Schizophrenics fared significantly worse on all outcome variables
      rehospitalization, which ranged from 17.7 to 23.4%. Bipolars had good
      psychosocial outcomes regardless of clinical outcome, while the two outcome
      domains were uncorrelated among schizophrenics and psychotic depressed.
      Schizophreniform patients had significantly better outcome than those with
      schizophrenia or schizoaffective disorder. Posthospital treatment was generally
      unrelated to outcome except that fewer rehospitalized schizophrenics received
      continuous treatment, and patients with psychotic depression with poorer
      psychosocial outcome received medication less frequently. These findings
      highlight the different treatment needs of these diagnostic groups, especially as
      regards the provision of more intensive rehabilitation for schizophrenic patients
      and the "poor-outcome" psychotic depressed.

PMID- 9242896
TI  - A pilot trial of adjunctive gabapentin in the treatment of bipolar disorder.
AB  - Several antiepileptic drugs (AEDs) have documented efficacy in the manic phase of
      bipolar disorder. To investigate the efficacy, tolerability, and safety of the
      new AED, gabapentin, in mania, we treated nine consecutive outpatients with
      bipolar I or II disorder by DSM-IV criteria who were experiencing hypomanic,
      manic, or mixed states inadequately responsive to standard mood stabilizers with
      open-label, adjunctive gabapentin. Response of manic symptoms was assessed
      monthly as none, minimal, moderate, or marked. Of the nine patients, seven
      displayed a moderate or marked reduction in manic symptoms by 1 month after
      addition of gabapentin, and an additional patient displayed moderate improvement
      after 3 months. Of these eight patients, six displayed continued antimanic
      responses for follow-up periods ranging from 1 to 7 months. Side effects were
      most commonly neurological, mild, and transient. Adjunctive gabapentin may have
      antimanic and mood-stabilizing effects in some patients with bipolar disorder and
      is generally well tolerated. Controlled studies of gabapentin in bipolar disorder
      appear to be warranted.

PMID- 9242897
TI  - Use of risperidone in delirium: case reports.
AB  - Traditionally, high-potency neuroleptics such as haloperidol have been used with
      success in the treatment of organic brain syndromes, but they have been
      associated with significant side effects such as EPS. We present the first case
      reports of a newer antipsychotic, risperidone, in the treatment of two delirious
      patients. Risperidone may prove to be an effective alternative to haloperidol in
      delirious patients, especially the elderly and the severely medically ill, who
      are more prone to adverse effects. Two case histories are presented, one of a 60
      year-old man and the other of a 14-year-old boy in whom delirium was successfully
      treated with low doses of risperidone.

PMID- 9242898
TI  - Late-onset anorexia nervosa in schizophrenia: a case report.
AB  - The authors report a case of a woman with chronic schizophrenia who developed
      anorexia nervosa in middle age. The reported rarity of this diagnostic
      combination and the need to be aware of treatment issues in all patients with
      coexisting psychoses and eating disorder symptoms are discussed.

PMID- 9242899
TI  - Three years on clomipramine: before and after brain SPECT study.
AB  - A case is presented of a patient diagnosed with attention deficit disorder,
      obsessive thinking, anger outbursts, and depression who had a SPECT study prior
      to treatment and after 3 years of treatment on clomipramine. The follow-up SPECT
      study showed marked improvement overall in the cerebral perfusion of the brain.
      At rest marked overactivity was noted in the anterior medial aspects of the
      frontal lobes, along with "patchy" (increased and decreased) uptake throughout
      the cortical and subcortical areas of the brain. After treatment for 3 years on
      clomipramine at 225 mg a day, the follow-up SPECT study revealed a normalization
      of activity in the anterior medial aspects of the frontal lobes as well as no
      patchy uptake cortically and subcortically as noted in the study prior to
      treatment. The clinical usefulness of the SPECT study as it relates to this case
      is discussed.

PMID- 9242900
TI  - From chemistry to biochemistry to catalysis to movement.
AB  - Mechanisms of chemical reaction can often be predicted by determining the
      dependence of the lifetime of reaction intermediates on the structure of the
      reactants. When there is no lifetime in the presence of another reactant or
      catalyst the reaction proceeds through an enforced concerted mechanism.
      Noncovalent binding interactions between enzymes and their substrates provide a
      major contribution to catalysis by decreasing entropy and by destabilizing the
      ground state relative to the transition state, as well as by covalent and
      noncovalent chemical interactions with the substrate. Movement in biological
      systems, such as muscle contraction and the active transport of ions, is
      generally brought about through a series of alternating chemical and vectorial
      steps that involve a series of changes in the specificity for catalysis of the
      chemical and vectorial reactions. These changes divide the overall reaction into
      segments so that neither the chemical nor the vectorial reaction will be
      completed unless the other is also completed.

PMID- 9242901
TI  - Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and
      protein enzymes.
AB  - A classic approach in biology, both organismal and cellular, is to compare
      morphologies in order to glean structural and functional commonalities. The
      comparative approach has also proven valuable on a molecular level. For example,
      phylogenetic comparisons of RNA sequences have led to determination of conserved
      secondary and even tertiary structures, and comparisons of protein structures
      have led to classifications of families of protein folds. Here we take this
      approach in a mechanistic direction, comparing protein and RNA enzymes. The aim
      of comparing RNA and protein enzymes is to learn about fundamental physical and
      chemical principles of biological catalysis. The more recently discovered RNA
      enzymes, or ribozymes, provide a distinct perspective on long-standing questions
      of biological catalysis. The differences described in this review have taught us
      about the aspects of RNA and proteins that are distinct, whereas the common
      features have helped us to understand the aspects that are fundamental to
      biological catalysis. This has allowed the framework that was put forth by Jencks
      for protein catalysts over 20 years ago (1) to be extended to RNA enzymes,
      generalized, and strengthened.

PMID- 9242902
TI  - Replication protein A: a heterotrimeric, single-stranded DNA-binding protein
      required for eukaryotic DNA metabolism.
AB  - Replication protein A [RPA; also known as replication factor A (RFA) and human
      single-stranded DNA-binding protein] is a single-stranded DNA-binding protein
      that is required for multiple processes in eukaryotic DNA metabolism, including
      DNA replication, DNA repair, and recombination. RPA homologues have been
      identified in all eukaryotic organisms examined and are all abundant
      heterotrimeric proteins composed of subunits of approximately 70, 30, and 14 kDa.
      Members of this family bind nonspecifically to single-stranded DNA and interact
      with and/or modify the activities of multiple proteins. In cells, RPA is
      phosphorylated by DNA-dependent protein kinase when RPA is bound to single
      stranded DNA (during S phase and after DNA damage). Phosphorylation of RPA may
      play a role in coordinating DNA metabolism in the cell. RPA may also have a role
      in modulating gene expression.

PMID- 9242903
TI  - Bacterial cell division and the Z ring.
AB  - Bacterial cell division occurs through the formation of an FtsZ ring (Z ring) at
      the site of division. The ring is composed of the tubulin-like FtsZ protein that
      has GTPase activity and the ability to polymerize in vitro. The Z ring is thought
      to function in vivo as a cytoskeletal element that is analogous to the
      contractile ring in many eukaryotic cells. Evidence suggests that the Z ring is
      utilized by all prokaryotic organisms for division and may also be used by some
      eukaryotic organelles. This review summarizes our present knowledge about the
      formation, function, and evolution of the Z ring in prokaryotic cell division.

PMID- 9242904
TI  - Basic mechanisms of transcript elongation and its regulation.
AB  - Ternary complexes of DNA-dependent RNA polymerase with its DNA template and
      nascent transcript are central intermediates in transcription. In recent years,
      several unusual biochemical reactions have been discovered that affect the
      progression of RNA polymerase in ternary complexes through various transcription
      units. These reactions can be signaled intrinsically, by nucleic acid sequences
      and the RNA polymerase, or extrinsically, by protein or other regulatory factors.
      These factors can affect any of these processes, including promoter proximal and
      promoter distal pausing in both prokaryotes and eukaryotes, and therefore play a
      central role in regulation of gene expression. In eukaryotic systems, at least
      two of these factors appear to be related to cellular transformation and human
      cancers. New models for the structure of ternary complexes, and for the mechanism
      by which they move along DNA, provide plausible explanations for novel
      biochemical reactions that have been observed. These models predict that RNA
      polymerase moves along DNA without the constant possibility of dissociation and
      consequent termination. A further prediction of these models is that the
      polymerase can move in a discontinuous or inchworm-like manner. Many direct
      predictions of these models have been confirmed. However, one feature of RNA
      chain elongation not predicted by the model is that the DNA sequence can
      determine whether the enzyme moves discontinuously or monotonically. In at least
      two cases, the encounter between the RNA polymerase and a DNA block to elongation
      appears to specifically induce a discontinuous mode of synthesis. These findings
      provide important new insights into the RNA chain elongation process and offer
      the prospect of understanding many significant biological regulatory systems at
      the molecular level.

PMID- 9242905
TI  - Polyadenylation of mRNA in prokaryotes.
AB  - The 3'-ends of both prokaryotic and eukaryotic mRNA are polyadenylated, but the
      poly(A) tracts of prokaryotic mRNA are generally shorter, ranging from 15 to 60
      adenylate residues and associated with only 2-60% of the molecules of a given
      mRNA species. The sites of polyadenylation of bacterial mRNA are diverse and
      include the 3'-ends of primary transcripts, the sites of endonucleolytic
      processing in the 3' untranslated and intercistronic regions, and sites within
      the coding regions of mRNA degradation products. The diversity of polyadenylation
      sites suggests that mRNA polyadenylation in prokaryotes is a relatively
      indiscriminate process that can occur at all mRNA's 3'-ends and does not require
      specific consensus sequences as in eukaryotes. Two poly(A) polymerases have been
      identified in Escherichia coli. They are encoded by unlinked genes, neither of
      which is essential for growth, suggesting significant functional overlap.
      Polyadenylation promotes the degradation of a regulatory RNA that inhibits the
      replication of bacterial plasmids and may play a similar role in the degradation
      of mRNA. However, under certain conditions, poly(A) tracts may lead to mRNA
      stabilization. Their ability to bind S1 ribosomal protein suggests that poly(A)
      tracts may also play a role in mRNA translation.

PMID- 9242906
TI  - Molecular basis for membrane phospholipid diversity: why are there so many
      lipids?
AB  - Phospholipids play multiple roles in cells by establishing the permeability
      barrier for cells and cell organelles, by providing the matrix for the assembly
      and function of a wide variety of catalytic processes, by acting as donors in the
      synthesis of macromolecules, and by actively influencing the functional
      properties of membrane-associated processes. The function, at the molecular
      level, of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin in
      specific cellular processes is reviewed, with a focus on the results of combined
      molecular genetic and biochemical studies in Escherichia coli. These results are
      compared with primarily biochemical data supporting similar functions for these
      phospholipids in eukaryotic organisms. The wide range of processes in which
      specific involvement of phospholipids has been documented explains the need for
      diversity in phospholipid structure and why there are so many membrane lipids.

PMID- 9242907
TI  - Molybdenum-cofactor-containing enzymes: structure and mechanism.
AB  - Molybdenum-containing enzymes catalyze basic metabolic reactions in the nitrogen,
      sulfur, and carbon cycles. With the exception of the nitrogenase cofactor,
      molybdenum is incorporated into proteins as the molybdenum cofactor that contains
      a mononuclear molybdenum atom coordinated to the sulfur atoms of a pterin
      derivative named molybdopterin. Certain microorganisms can also utilize tungsten
      in a similar fashion. Molybdenum-cofactor-containing enzymes catalyze the
      transfer of an oxygen atom, ultimately derived from or incorporated into water,
      to or from a substrate in a two-electron redox reaction. On the basis of sequence
      alignments and spectroscopic properties, four families of molybdenum-cofactor
      containing enzymes have been identified. The available crystallographic
      structures for members of these families are discussed within the framework of
      the active site structure and catalytic mechanisms of molybdenum-cofactor
      containing enzymes. Although the function of the molybdopterin ligand has not yet
      been conclusively established, interactions of this ligand with the coordinated
      metal are sensitive to the oxidation state, indicating that the molybdopterin may
      be directly involved in the enzymatic mechanism.

PMID- 9242908
TI  - Structure-based perspectives on B12-dependent enzymes.
AB  - Two X-ray structures of cobalamin (B12) bound to proteins have now been
      determined. These structures reveal that the B12 cofactor undergoes a major
      conformational change on binding to the apoenzymes of methionine synthase and
      methylmalonyl-coenzyme A mutase: The dimethylbenzimidazole ligand to the cobalt
      is displaced by a histidine residue from the protein. Two methyltransferases from
      archaebacteria that catalyze methylation of mercaptoethanesulfonate (coenzyme M)
      during methanogenesis have also been shown to contain histidine-ligated
      cobamides. In corrinoid iron-sulfur methyltransferases from acetogenic and
      methanogenic organisms, benzimidazole is dissociated from cobalt, but without
      replacement by histidine. Thus, dimethylbenzimidazole displacement appears to be
      an emerging theme in cobamide-containing methyltransferases. In methionine
      synthase, the best studied of the methyltransferases, the histidine ligand
      appears to be required for competent methyl transfer between methyl
      tetrahydrofolate and homocysteine but dissociates for reductive reactivation of
      the inactive oxidized enzyme. Replacement of dimethylbenzimidazole by histidine
      may allow switching between the catalytic and activation cycles. The best
      characterized B12-dependent mutases that catalyze carbon skeleton rearrangement,
      for which methylmalonyl-coenzyme A mutase is the prototype, also bind cobalamin
      cofactors with histidine as the cobalt ligand, although other cobalamin-dependent
      mutases do not appear to utilize histidine ligation. It is intriguing to find
      that mutases, which catalyze homolytic rather than heterolytic cleavage of the
      carbon-cobalt bond, can use this structural motif. In methylmalonylCoA mutase a
      significant feature, which may be important in facilitating homolytic cleavage,
      is the long cobalt-nitrogen bond linking histidine to the co-factor. The
      intermediate radical species generated in catalysis are sequestered in the
      relatively hydrophilic core of an alpha/beta barrel domain of the mutase.

PMID- 9242909
TI  - Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins.
AB  - Modification of Ser and Thr residues by attachment of O-linked N-acetylglucos
      amine [Ser(Thr)-O-GlcNAcylation] to eukaryotic nuclear and cytosolic proteins is
      as dynamic and possibly as abundant as Ser(Thr) phosphorylation. Known O
      GlcNAcylated proteins include cytoskeletal proteins and their regulatory
      proteins; viral proteins; nuclear-pore, heat-shock, tumor-suppressor, and
      nuclearoncogene proteins; RNA polymerase II catalytic subunit; and a multitude of
      transcription factors. Although functionally diverse, all of these proteins are
      also phosphoproteins. Most O-GlcNAcylated proteins form highly regulated
      multimeric associations that are dependent upon their posttranslational
      modifications. Evidence is mounting that O-GlcNAcylation is an important
      regulatory modification that may have a reciprocal relationship with O
      phosphorylation and may modulate many biological processes in eukaryotes.

PMID- 9242910
TI  - D-amino acids in animal peptides.
AB  - D-amino acids have been detected in a variety of peptides synthesized by animal
      cells. These include opiate and antimicrobial peptides from amphibian skin,
      neuropeptides from snail ganglia, a hormone from crustaceans, and a constituent
      of a spider venom. cDNA cloning has shown that at those positions where a D-amino
      acid is found in the end-product, a normal codon for the corresponding L-amino
      acid is present. This implies that the D-residues are formed from L-amino acids
      by a posttranslational reaction. A prototype enzyme catalyzing such a reaction
      has recently been isolated from the venom of the funnel web spider.

PMID- 9242911
TI  - Herpes simplex virus DNA replication.
AB  - The Herpesviridae comprise a large class of animal viruses of considerable public
      health importance. Of the Herpesviridae, replication of herpes simplex virustype
      1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome
      contains three origins of DNA replication and approximately 75 open-reading
      frames. Of these frames, seven encode proteins that are required for
      originspecific DNA replication. These proteins include a processive heterodimeric
      DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome
      with 5'-3' DNA helicase and primase activities, and an origin-binding protein
      with 3'-5' DNA helicase activity. HSV-1 also encodes a set of enzymes involved in
      nucleotide metabolism that are not required for viral replication in cultured
      cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide
      reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA
      glycosylase. Host enzymes, notably DNA polymerase alpha-primase, DNA ligase I,
      and topoisomerase II, are probably also required. Following circularization of
      the linear viral genome, DNA replication very likely proceeds in two phases: an
      initial phase of theta replication, initiated at one or more of the origins,
      followed by a rolling-circle mode of replication. The latter generates
      concatemers that are cleaved and packaged into infectious viral particles. The
      rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by
      a complex containing several of the HSV-1 encoded DNA replication enzymes.
      Reconstitution of the theta phase has thus far eluded workers in the field and
      remains a challenge for the future.

PMID- 9242912
TI  - Models of amyloid seeding in Alzheimer's disease and scrapie: mechanistic truths
      and physiological consequences of the time-dependent solubility of amyloid
      proteins.
AB  - Ordered protein aggregation in the brain is a hallmark of Alzheimer's disease and
      scrapie. The disease-specific amyloid fibrils comprise primarily a single
      protein, amyloid beta, in Alzheimer's disease, and the prion protein in scrapie.
      These proteins can be induced to form aggregates in vitro that are
      indistinguishable from brain-derived fibrils. Consequently, much effort has been
      invested in the development of in vitro model systems to study the details of the
      aggregation processes and the effects of endogenous molecules that have been
      implicated in disease. Selected studies of this type are reviewed herein. A
      simple mechanistic model has emerged for both processes that involves a
      nucleation-dependent polymerization. This mechanism dictates that aggregation is
      dependent on protein concentration and time. Furthermore, amyloid formation can
      be seeded by a preformed fibril. The physiological consequences of this mechanism
      are discussed.

PMID- 9242913
TI  - Mitochondrial DNA maintenance in vertebrates.
AB  - The discovery that mutations in mitochondrial DNA (mtDNA) can be pathogenic in
      humans has increased interest in understanding mtDNA maintenance. The functional
      state of mtDNA requires a great number of factors for gene expression, DNA
      replication, and DNA repair. These processes are ultimately controlled by the
      cell nucleus, because the requisite proteins are all encoded by nuclear genes and
      imported into the mitochondrion. DNA replication and transcription are linked in
      vertebrate mitochondria because RNA transcripts initiated at the light-strand
      promoter are the primers for mtDNA replication at the heavy-strand origin. Study
      of this transcription-primed DNA replication mechanism has led to isolation of
      key factors involved in mtDNA replication and transcription and to elucidation of
      unique nucleic acid structures formed at this origin. Because features of a
      transcription-primed mechanism appear to be conserved in vertebrates, a general
      model for initiation of vertebrate heavy-strand DNA synthesis is proposed. In
      many organisms, mtDNA maintenance requires not only faithful mtDNA replication,
      but also mtDNA repair and recombination. The extent to which these latter two
      processes are involved in mtDNA maintenance in vertebrates is also appraised.

PMID- 9242914
TI  - Target site selection in transposition.
AB  - Transposable elements are discrete mobile DNA segments that can insert into non
      homologous target sites. Diverse patterns of target site selectivity are
      observed: Some elements display considerable target site selectivity and others
      display little obvious selectivity, although none appears to be truly "random." A
      variety of mechanisms for target site selection are used: Some elements use
      direct interactions between the recombinase and target DNA whereas other elements
      depend upon interactions with accessory proteins that communicate both with the
      target DNA and the recombinase. The study of target site selectivity is useful in
      probing recombination mechanisms, in studying genome structure and function, and
      also in providing tools for genome manipulation.

PMID- 9242915
TI  - Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and
      phospholipase D.
AB  - This review focuses on two phospholipase activities involved in eukaryotic signal
      transduction. The action of the phosphatidylinositol-specific phospholipase C
      enzymes produces two well-characterized second messengers, inositol 1,4,5
      trisphosphate and diacylglycerol. This discussion emphasizes recent advances in
      elucidation of the mechanisms of regulation and catalysis of the various isoforms
      of these enzymes. These are especially related to structural information now
      available for a phospholipase C delta isozyme. Phospholipase D hydrolyzes
      phospholipids to produce phosphatidic acid and the respective head group. A
      perspective of selected past studies is related to emerging molecular
      characterization of purified and cloned phospholipases D. Evidence for various
      stimulatory agents (two small G protein families, protein kinase C, and
      phosphoinositides) suggests complex regulatory mechanisms, and some studies
      suggest a role for this enzyme activity in intracellular membrane traffic.

PMID- 9242916
TI  - Clathrin-coated vesicle formation and protein sorting: an integrated process.
AB  - Clathrin-coated vesicles were the first discovered and remain the most
      extensively characterized transport vesicles. They mediate endocytosis of
      transmembrane receptors and transport of newly synthesized lysosomal hydrolases
      from the trans-Golgi network to the lysosome. Cell-free assays for coat assembly,
      membrane binding, and coated vesicle budding have provided detailed functional
      and structural information about how the major coat constituents, clathrin and
      the adaptor protein complexes, interact with each other, with membranes, and with
      the sorting signals found on cargo molecules. Coat constituents not only serve to
      shape the budding vesicle, but also play a direct role in the packaging of cargo,
      suggesting that protein sorting and vesicle budding are functionally integrated.
      The functional interplay between the coated vesicle machinery and its cargo could
      ensure sorting fidelity and packaging efficiency and might enable modulation of
      vesicular trafficking in response to demand.

PMID- 9242917
TI  - Protein folding: the endgame.
AB  - The last stage of protein folding, the "endgame," involves the ordering of amino
      acid side-chains into a well defined and closely packed configuration. We review
      a number of topics related to this process. We first describe how the observed
      packing in protein crystal structures is measured. Such measurements show that
      the protein interior is packed exceptionally tightly, more so than the protein
      surface or surrounding solvent and even more efficiently than crystals of simple
      organic molecules. In vitro protein folding experiments also show that the
      protein is close-packed in solution and that the tight packing and intercalation
      of side-chains is a final and essential step in the folding pathway. These
      experimental observations, in turn, suggest that a folded protein structure can
      be described as a kind of three-dimensional jigsaw puzzle and that predicting
      side-chain packing is possible in the sense of solving this puzzle. The major
      difficulty that must be overcome in predicting side-chain packing is a
      combinatorial "explosion" in the number of possible configurations. There has
      been much recent progress towards overcoming this problem, and we survey a
      variety of the approaches. These approaches differ principally in whether they
      use ab initio (physical) or more knowledge-based methods, how they divide up and
      search conformational space, and how they evaluate candidate configurations
      (using scoring functions). The accuracy of side-chain prediction depends
      crucially on the (assumed) positioning of the main-chain. Methods for predicting
      main-chain conformation are, in a sense, not as developed as that for side
      chains. We conclude by surveying these methods. As with side-chain prediction,
      there are a great variety of approaches, which differ in how they divide up and
      search space and in how they score candidate conformations.

PMID- 9242918
TI  - Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression.
AB  - Phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is a key enzyme in
      the synthesis of glucose in the liver and kidney and of glyceride-glycerol in
      white adipose tissue and the small intestine. The gene for the cytosolic form of
      PEPCK (PEPCK-C) is acutely regulated by a variety of dietary and hormonal
      signals, which result in alteration of synthesis of the enzyme. Major factors
      that increase PEPCK-C gene expression include cyclic AMP, glucocorticoids, and
      thyroid hormone, whereas insulin inhibits this process. PEPCK-C is absent in
      fetal liver but appears at birth, concomitant with the capacity for
      gluconeogenesis. Regulatory elements that control transcription of the PEPCK-C
      gene in liver, kidney, and adipose tissue have been delineated, and many of the
      transcription factors that bind to these elements have been identified.
      Transgenic mice have been especially useful in elucidating the physiological
      roles of specific sequence elements in the PEPCK-C gene promoter and in
      demonstrating the key role played at these sites by the isoforms of CAAT/enhancer
      binding protein in patterning of PEPCK-C gene expression during the perinatal
      period. The PEPCK-C gene provides a model for the metabolic control of gene
      transcription.

PMID- 9242919
TI  - Acyl-coenzyme A:cholesterol acyltransferase.
AB  - Due to its presumed role in regulating cellular cholesterol homeostasis, and in
      various pathophysiological conditions, acyl-coenzyme A:cholesterol
      acyltransferase (ACAT) has attracted much attention. Cloning the ACAT gene
      provides the necessary tool to advance molecular studies of this enzyme. The
      topics reviewed in this chapter include the pathophysiological roles of ACAT, the
      biochemistry and molecular biology of the ACAT protein and the ACAT gene, and the
      mode of regulation by sterol or nonsterol agents in mammalian cells. In addition,
      we present a working model linking the presumed allosteric property of ACAT with
      cholesterol trafficking into and out of the endoplasmic reticulum.

PMID- 9242920
TI  - G protein mechanisms: insights from structural analysis.
AB  - This review is concerned with the structures and mechanisms of a superfamily of
      regulatory GTP hydrolases (G proteins). G proteins include Ras and its close
      homologs, translation elongation factors, and heterotrimeric G proteins. These
      proteins share a common structural core, exemplified by that of p21ras (Ras), and
      significant sequence identity, suggesting a common evolutionary origin. Three
      dimensional structures of members of the G protein superfamily are considered in
      light of other biochemical findings about the function of these proteins.
      Relationships among G protein structures are discussed, and factors contributing
      to their low intrinsic rate of GTP hydrolysis are considered. Comparison of GTP-
      and GDP-bound conformations of G proteins reveals how specific contacts between
      the gamma-phosphate of GTP and the switch II region stabilize potential effector
      binding sites and how GTP hydrolysis results in collapse (or reordering) of these
      surfaces. A GTPase-activating protein probably binds to and stabilizes the
      conformation of its cognate G protein that recognizes the transition state for
      hydrolysis, and may insert a catalytic residue into the G protein active site.
      Inhibitors of nucleotide release, such as the beta gamma subunit of a
      heterotrimeric G protein, bind selectively to and stabilize the GDP-bound state.
      Release factors, such as the translation elongation factor, Ts, also recognize
      the switch regions and destabilize the Mg(2+)-binding site, thereby promoting GDP
      release. G protein-coupled receptors are expected to operate by a somewhat
      different mechanism, given that the GDP-bound form of many G protein alpha
      subunits does not contain bound Mg2+.

PMID- 9242921
TI  - Ribosomes and translation.
AB  - The ribosome is a large multifunctional complex composed of both RNA and
      proteins. Biophysical methods are yielding low-resolution structures of the
      overall architecture of ribosomes, and high-resolution structures of individual
      proteins and segments of rRNA. Accumulating evidence suggests that the ribosomal
      RNAs play central roles in the critical ribosomal functions of tRNA selection and
      binding, translocation, and peptidyl transferase. Biochemical and genetic
      approaches have identified specific functional interactions involving conserved
      nucleotides in 16S and 23S rRNA. The results obtained by these quite different
      approaches have begun to converge and promise to yield an unprecedented view of
      the mechanism of translation in the coming years.

PMID- 9242922
TI  - The ATP synthase--a splendid molecular machine.
AB  - An X-ray structure of the F1 portion of the mitochondrial ATP synthase shows
      asymmetry and differences in nucleotide binding of the catalytic beta subunits
      that support the binding change mechanism with an internal rotation of the gamma
      subunit. Other structural and mutational probes of the F1 and F0 portions of the
      ATP synthase are reviewed, together with kinetic and other evaluations of
      catalytic site occupancy and behavior during hydrolysis or synthesis of ATP.
      Subunit function as related to proton translocation and rotational catalysis is
      considered. Physical demonstrations of the gamma subunit rotation have been
      achieved. The findings have implications for other enzymatic catalyses.

PMID- 9242923
TI  - Subtractive cloning: past, present, and future.
AB  - Subtractive cloning is a powerful technique for isolating genes expressed or
      present in one cell population but not in another. This method and a related one
      termed positive selection have their origins in nucleic acid reassociation
      techniques. We discuss the history of subtractive techniques, and fundamental
      information about the nucleic acid composition of cells that came out of
      reassociation analyses. We then explore current techniques for subtractive
      cloning and positive selection, discussing the merits of each. These techniques
      include cDNA library-based techniques and PCR-based techniques. Finally, we
      briefly discuss the future of subtractive cloning and new approaches that may
      augment or supersede current methods.

PMID- 9242924
TI  - Force effects on biochemical kinetics.
AB  - Force is an important component in the proper functioning of tissues and cells.
      In processes ranging from the contraction of muscles to the alignment of
      chromosomes at the metaphase plate, forces must be adjusted to the proper levels
      by cells. At the molecular level, it is clear that the motor molecules and other
      enzymes must respond to changes in mechanical forces by altering enzymatic
      function. Recent technical advances, primarily the atomic force microscope and
      laser tweezers, enable us to measure forces at the single molecule level to test
      how force is transduced into a change in enzyme activity. A priori, four basic
      mechanisms of coupling enzyme rate and force are considered. The mechanisms
      extend from the cellular to the molecular level. For example, polymer assembly
      rates and cytoskeletal matrix concentration are potentially modified by force in
      ways that feed back on critical enzyme rates. In studies of the known
      mechanosensitive enzymes, myosin and other motors, the bacterial flagellar rotor,
      and the F0F1 ATPase, the molecular mechanisms used to transduce force changes
      into activity changes have not been clearly defined, although it is reasonable to
      speculate about the nature of these mechanisms from the atomic structures and
      nanometer measurements of movement.

PMID- 9242925
TI  - Transcriptional regulation by cyclic AMP.
AB  - A number of hormones and growth factors have been shown to stimulate target cells
      via second messenger pathways that in turn regulate the phosphorylation of
      specific nuclear factors. The second messenger cyclic AMP, for example, regulates
      a striking number of physiologic processes, including intermediary metabolism,
      cellular proliferation, and neuronal signaling, by altering basic patterns of
      gene expression. Our understanding of cyclic AMP signaling in the nucleus has
      expanded considerably over the past decade, owing in large part to the
      characterization of cyclic AMP-responsive promoter elements, transcription
      factors that bind them, and signal-dependent coactivators that mediate target
      gene induction. More importantly, these studies have revealed new insights into
      biological problems as diverse as biological clocks and long-term memory. The
      purpose of this review is to describe the components of the cyclic AMP response
      unit and to analyze how these components cooperate to induce target gene
      expression in response to hormonal stimulation.

PMID- 9242926
TI  - The molecular structure of cell adhesion molecules.
AB  - Considerable advances have been made in our knowledge of the molecular structure
      of cell adhesion molecules, their binding sites, and adhesion complexes. For the
      cadherins, protein zero, and CD2, additional experimental data support the
      insights obtained from structural analysis of their domains and molecular models
      of their adhesion complexes. For neural cell adhesion molecules, L1, fibronectin,
      tenascin-C, integrins, and vascular cell adhesion molecules, the molecular
      structure of domains, and in most cases their binding sites, have been
      elucidated. The substrate recognition sites in some of these molecules possess
      rate constants for association and dissociation that permit both rapid cell
      migration and, through avidity, high-affinity cell-cell interactions.

PMID- 9242927
TI  - Protein import into mitochondria.
AB  - Mitochondria import many hundreds of different proteins that are encoded by
      nuclear genes. These proteins are targeted to the mitochondria, translocated
      through the mitochondrial membranes, and sorted to the different mitochondrial
      subcompartments. Separate translocases in the mitochondrial outer membrane (TOM
      complex) and in the inner membrane (TIM complex) facilitate recognition of
      preproteins and transport across the two membranes. Factors in the cytosol assist
      in targeting of preproteins. Protein components in the matrix partake in
      energetically driving translocation in a reaction that depends on the membrane
      potential and matrix-ATP. Molecular chaperones in the matrix exert multiple
      functions in translocation, sorting, folding, and assembly of newly imported
      proteins.

PMID- 9242928
TI  - An urgent need to include blood substitute as a priority area in any national
      policies on blood supply.

PMID- 9242929
TI  - Facilitated oxygen transport with modified and encapsulated hemoglobins across
      non-flowing solution membrane.
AB  - The oxygen-transporting capability of modified and encapsulated hemoglobins and
      red cells is discussed from a physico-chemical standpoint in order to design
      oxygen-delivering fluids. The oxygen diffusion coefficient toward oxygen
      deficient sites was estimated by measuring the oxygen flux across thin solution
      membranes of hemoglobin, polymerized hemoglobin, liposome-encapsulated
      hemoglobin, and red cells. Oxygen flux was enhanced several times over that of
      nitrogen for the hemoglobin and red cell solution with ca [Hb] = 10 and 15 g/dl,
      respectively. The enhancement in the oxygen diffusion is ascribed to the
      facilitated transport of oxygen via the hemoglobins. This was in contrast to the
      simple and physical oxygen-diffusivity in response to its concentration gradient,
      in the absence of hemoglobins. The flux of the oxygen transport was in the order
      of hemoglobin > red cells > polymerized hemoglobin > encapsulated hemoglobin,
      which was ascribed to the facilitated transport efficiencies of oxygen with
      hemoglobins in a non-flowing or stationary solution.

PMID- 9242930
TI  - Complement activation and thromboxane secretion by liposome-encapsulated
      hemoglobin in rats in vivo: inhibition by soluble complement receptor type 1.
AB  - Intravenous administration of liposome-encapsulated hemoglobin (LEH) in rats led
      to an early (within 15 min) decline of hemolytic complement (C) activity in the
      plasma along with a significant, parallel rise in thromboxane B2 (TXB2) levels.
      The TXB2 response was inhibited by co-administration of soluble C receptor type 1
      (sCR1) with LEH, as well as by C depletion with cobra venom factor. These
      observations provide evidence for a causal relationship between LEH-induced C
      activation and TXB2 release, and suggest that sCR1 could be useful in attenuating
      the acute respiratory, hematological and hemodynamic side effects of LEH
      described earlier in the rat.

PMID- 9242931
TI  - The oxygen carrying capability of hemoglobin vesicles evaluated in rat exchange
      transfusion models.
AB  - To evaluate the oxygen transporting capability of Hemoglobin vesicles (HbV) the
      physiological responses to 40% and 90% exchange transfusions with HbV in
      anesthetized rat were observed. Hb concentration of HbV dispersions is 10 g/dL.
      HbV dispersed in phosphate buffered saline and HbV dispersed in 5% albumin
      solution were used as samples for 40% and 90% exchange transfusions,
      respectively. HbV surface-modified with polyoxyethylene (HbV-Poe) was also used
      in the 90% exchange transfusion. As controls, phosphate buffered saline, 5%
      albumin solution, and HbV containing methemoglobin and therefore deprived of
      oxygen transporting capabilities (metHbV) were administered as non-oxygen
      carrying fluids and washed rat red blood cells (ratRBC) as an oxygen carrying
      fluid. Measurements included mean arterial pressure, arterial blood gas analyses,
      aortic blood flow and renal cortical tissue oxygen tension. At the completion of
      the exchange transfusion renal cortical tissue oxygen tensions along with oxygen
      delivery and consumption were sustained almost equally well with the HbV
      dispersion compared to the washed rat red blood cell dispersion, but declined
      significantly in the phosphate buffered saline and albumin solutions. These
      results indicated that the oxygen transporting capability of HbV was almost
      equivalent to that of rat red blood cells. In the HbV-Poe group, aortic blood
      flow was sustained higher in comparison to the HbV group. As for the blood gas
      parameters, pH and venous oxygen tensions in the HbV-Poe group tended to be
      higher than those in the HbV group.

PMID- 9242932
TI  - Kinetic aspects of polyelectrolyte adsorption: adsorption of chitin derivatives
      onto liposomes as a model system.
AB  - Carboxymethylchitin (CMC) and Carboxymethyl/Glycolchitin (CO) have been adsorbed
      onto liposomes at physiological ionic strength (I) and pH using phosphate buffer
      saline (PBS, I = 154 mM, pH = 7.4). Adsorption isotherms at different polymer
      weight average molecular weights (Mw), for Positive ([+]) or high surface
      affinity liposomes (DSPC:CHOL:DMTAP, 5:4:1), and Neutral ([N]) or low surface
      affinity liposomes (DSPC:CHOL, 1:1), have been obtained at T = 25 degrees C. For
      all CMCs, the adsorbed amount increases with polymer concentration ([P]zero) and
      no true plateau is observed. The CMC Mw = 4.19 x 10(5) adsorbed on a positive
      surface fits Langmuir kinetics with maximal coverage gamma max = 325.4
      micrograms/mg (polymer/lipid), and inverse of equilibrium constant K* = 4.743 x
      10(-4) mg/ml. For all isotherms the predicted amount of polymer needed to coat
      the entire surface based on the Radius of Gyration (Rg) is inferior to the amount
      adsorbed. This fact in conjunction with the dependence of gamma max on the number
      of adsorption shots, suggests that the adsorption is not thermodynamically but
      kinetically controlled.

PMID- 9242933
TI  - Effect of liposome encapsulated hemoglobin "neo red cells" on severe hemorrhagic
      shock.
AB  - We induced shock by exsanguination and administered Neo Red Cells (NRC) after 30
      minutes to experimentally examine the efficacy of NRC on severe shock with
      respect to hemodynamics and oxygen transport capacity. Seven beagles were used
      for this experiment. After intravenous anesthesia, intratracheal intubation was
      performed, and inhalation of 50% oxygen was administered. Animals were
      exsanguinated through a vein at a rate of 30 mL/min. Animals showing systolic
      blood pressure of 60 to 69 mmHg were regarded as being in shock. After animals
      were left untreated for 30 minutes, NRC was administered. This was then repeated.
      Administration of NRC at a 1.5-fold dose compared to the exsanguinated blood
      volume was required for animals to recover from shock. Animals tolerated shock 3
      times, but did not recover from the 4th shock. Although NRC with approximately
      one third the viscosity of whole blood was administered, vascular resistance was
      increased and cardiac output was decreased, resulting in progression of heart
      failure. In addition, oxygen consumption increased with shock. NRC satisfied
      oxygen requirements by compensating for the decrease in cardiac output with an
      increase in AV difference, but erythrocytes were insufficient to increase
      difference in arterial and venous oxygen content (AV difference), and did not
      supply sufficient volume of oxygen.

PMID- 9242934
TI  - Viscosity measurements for LEH suspended in different plasma expanders.
AB  - To investigate the possibility of hemodilution with oxygen carrying fluid, we
      measured the viscosity effects of LEH which was suspended in different weight
      percentage of plasma expanders for different shear rates. All of LEH/Plasma
      expander suspensions show shear thinning flow behavior, and the viscosity of
      those suspensions increase with increased the weight percentage of each expander
      in suspensions for a fixed shear rate. Compared the viscosity data to those of
      human blood at 40% of hematocrit, LEH/albumin suspensions contained with 4% to 8%
      of albumin are the most suitable, whereas LEH/dextran (Dex) suspensions contained
      with 6% Dex70c is the least favorable suspension media for LEH. In point of
      viscosity effects, hemodilution with LEH/albumin or LEH/0.9% oxypolygelatin (Gel)
      may be valuable for further testing their efficacy in animal model.

PMID- 9242935
TI  - Neo red cell as an organ preservation solution.
AB  - Neo red cell (NRC) was derived from outdated human red cells. The following
      experimental work has been done in order to investigate if NRC is valid for organ
      preservation. Hearts were obtained from male Lewis rat (250-350 g body weight).
      Heart transplantation was performed as Ono-Lindsey's method after 1, 3, 6, 12 and
      24 hours simple cold storage. Rats were divided into two groups. Group 1;
      original NRC as preservation solution, Group 2; modified NRC (NRC suspended with
      UW solution) as preservation solution. After 1, 3, and 6 hour cold ischemic
      storage, the transplanted hearts in both groups showed contraction immediately
      after declamping the aorta and the pulmonary artery. After 12 and 24 hour
      preservation, the transplanted hearts in group 2 showed contraction. Myocardial
      ATP levels after 6, 12, 24 hours cold storage compared with 0 hour were 62.3%,
      28.3%, 32.8% in group 1 respectively. On the contrary, myocardial ATP levels were
      87.2%, 57.6%, 52.2% in group 2 respectively. After 24 hour preservation,
      pathological change was not remarkable between the two groups. Results of the
      prolonged preservation time and the myocardial ATP changes suggest that there is
      a possibility for effective use of NRC not only as blood substitute but also
      organ preservation solution.

PMID- 9242936
TI  - Development of neo red cells (NRC) with the enzymatic reduction system of
      methemoglobin.
AB  - To assess the oxygen transport capacity and safety of Neo Red Cells (NRC) with
      the enzymatic reduction system of methemoglobin in vitro and in experimental
      animals. Stroma free hemoglobin (SFH) prepared without damage of enzymes from
      outdated human red blood cells, together with inositol hexaphosphate as an
      allosteric effector, NAD as a coenzyme and glucose, adenine and inosine as a
      substrate was encapsulated within liposomes composed of hydrogenated soy
      phosphatidylcholine, cholesterol, myristic acid and alpha-tocopherol in the ratio
      of 7:7:2:0.28 respectively. NRC thus prepared with a mean diameter of 220 nm,
      encapsulation efficiency of 1.3 g-Hb:1 g-lipid and P50O2 of 50-60 mmHg were then
      coated with polyethylene glycol bound to hydrogenated soy
      phosphatidylethanolamine as a surface modifier to prevent aggregation of NRC in
      plasma. The methemoglobin formation of the NRC with enzymatic reduction system
      were evaluated by in-vitro examination and exchange transfusion with rats as in
      vivo examination, then the methemoglobin formation was reduced from 1%/hr to
      0.4%/hr by the addition of methemoglobin reduction system. The generation of the
      pyruvate and the lactate were observed within the NRC with enzymatic reduction
      system, then the activation of the Embden-Meyerhof pathway was confirmed. And we
      concerned about the availability of the NRC as a perfusate for the
      cardiopulmonary bypass during moderate or profound hypothermia, then we evaluated
      the oxygen transporting efficiency and capacity of the NRC under the using of the
      artificial lung system in vitro examination. The present investigation suggest
      that the effectiveness of the NRC with enzymatic reduction system, they
      restrained the formation of methemoglobin and they are efficient oxygen carriers
      as a perfusate of the artificial lung, and we suggest the new extracorporeal
      circulation system using of the NRC as a perfusate for the cardiopulmonary
      bypass.

PMID- 9242937
TI  - Willem J. Kolff, MD: accomplishments beyond standard measurements.

PMID- 9242938
TI  - Cost considerations for long-term mechanical circulatory support.

PMID- 9242940
TI  - Feasibility of a photosynthetic artificial lung.
AB  - The success of extracorporeal membrane oxygenation (ECMO) for the treatment of
      acute respiratory failure has led to consideration of the development of a more
      portable, and perhaps even implantable, artificial lung. The authors suggest a
      bioregenerative life support system that includes a photo-synthetic organism that
      can remove CO2 and produce O2 in the presence of an energy source. To build a
      model of such a photosynthetic artificial lung, the photosynthetic capability of
      a high temperature strain of the algae Chlorella pyrenoidosa was maximized at a
      cell density of 25 million cells/ml to serve as the O2 producer and CO2 remover.
      The "patient" in this model was comprised of 1 L of medium or 350 ml of blood,
      interfaced with the photosynthetic system across a gas transfer membrane. The
      experiments demonstrated the ability of the plant cells to supply O2 and remove
      CO2 from the "patient" with a maximum rate of 0.55 mmoles/L/hr under the most
      favorable measured operating conditions. The projected rate of 1.0 mmoles/L/hr
      required for physiologic applications is not totally ab absurd idea, with a
      slightly modified set-up. Modifications may be in the form of regulating the
      photosynthetic pathway or genetically engineering a hybrid strain with enhanced
      O2 producing and suppressed photoinhibition capacity.

PMID- 9242939
TI  - Ice formation in isolated human hepatocytes and human liver tissue.
AB  - Cryopreservation of isolated cells and tissue slices of human liver is required
      to furnish extracorporeal bioartificial liver devices with a ready supply of
      hepatocytes, and to create in vitro drug metabolism and toxicity models. Although
      both the bioartificial liver and many current biotoxicity models are based on
      reconstructing organ functions from single isolated hepatocytes, tissue slices
      offer an in vitro system that may more closely resemble the in vivo situation of
      the cells because of cell-cell and cell-extracellular matrix interactions.
      However, successful cryopreservation of both cellular and tissue level systems
      requires an increased understanding of the fundamental mechanisms involved in the
      response of the liver and its cells to freezing stress. This study investigates
      the biophysical mechanisms of water transport and intracellular ice formation
      during freezing in both isolated human hepatocytes and whole liver tissue. The
      effects of cooling rate on individual cells were measured using a cryomicroscope.
      Biophysical parameters governing water transport (Lpg = 2.8 microns/min-atm and
      ELp = 79 kcal/mole) and intracellular heterogeneous ice nucleation (omega het =
      1.08 x 10(9) m-2s-1 and kappa het = 1.04 x 10(9) K5) were determined. These
      parameters were then incorporated into a theoretical Krogh cylinder model
      developed to simulate water transport and ice formation in intact liver tissue.
      Model simulations indicated that the cellular compartment of the Krogh model
      maintained more water than isolated cells under the same freezing conditions. As
      a result, intracellular ice nucleation occurred at lower cooling rates in the
      Krogh model than in isolated cells. Furthermore, very rapid cooling rates (1000
      degrees C/min) showed a depression of heterogeneous nucleation and a shift toward
      homogeneous nucleation. The results of this study are in qualitative agreement
      with the findings of a previous experimental study of the response to freezing of
      intact human liver.

PMID- 9242941
TI  - In vivo evaluation of an extracorporeal pediatric centrifugal blood pump.
AB  - This paper summarizes the authors' in vivo experience in evaluating a miniature
      centrifugal blood pump designed for pediatric/neonatal ventricular support. Left
      ventricular bypass was accomplished in two adult sheep and five juvenile lambs
      (5.5-80.0 kg) via either central (left ventricle to carotid artery) or peripheral
      (jugular vein to carotid artery) cannulation. Animals were weaned from mechanical
      ventilation and continuously monitored. Hemodynamic parameters remained within a
      normal range over the duration of the bypass. Two of five lambs were electively
      killed at 8, and 76 hours; the remaining three lambs died from respiratory
      complications at 33, 44, and 156 hours. There were no mechanical complications,
      and blood seal integrity was confirmed beyond 6 days. The pump speed was
      maintained at 3,000-4,500 rpm with pump flow rates between 0.4-1.5 L/min. Average
      plasma free hemoglobin was below 20 mg/dl in the five lamb experiments. Renal,
      hepatic, and hematologic indices also remained within physiologic ranges.
      Histopathologic analyses of major organs revealed renal cortical infarctions in
      two of five lambs. Examination of the pump surfaces after explant indicated small
      areas of thrombus in the housing adjacent to the outflow ports in two
      experiments. These encouraging results support further testing and refinement of
      this miniature centrifugal pump.

PMID- 9242943
TI  - A simple method to monitor the dose of hemodialysis.
AB  - A practical and inexpensive method to measure the dose of dialysis without any
      laboratory tests is described. A prospective study was performed that suggested
      that the volume of blood treated during hemodialysis, corrected for postdialysis
      body weight (CBVpost), can be used as a simple method to measure dose of
      dialysis. In this study the dose of dialysis, measured as Kt/Vurea, and the
      volume of blood dialyzed, were compared for 195 hemodialysis treatments. There
      was a strong positive correlation between Kt/Vurea and CBVpost in the entire
      group of patients (r = 0.78). However, this correlation was strongest for
      traditional dialysis using dialyzers with a urea clearance of 170-180 ml/min (r =
      0.82) than for other dialyzers.

PMID- 9242942
TI  - Evaluation of the capabilities of a hemoglobin vesicle as an artificial oxygen
      carrier in a rat exchange transfusion model.
AB  - Encapsulation of hemoglobin within a liposome is one of the strategies in the
      development of artificial oxygen carriers. It maintains the oxygen transporting
      properties of hemoglobin and, at the same time, eliminates the side effects of
      cell free hemoglobin. Hemoglobin vesicles (HbV) are a type of liposome
      encapsulated hemoglobin. They have a particle size of approximately 250 nm, a
      hemoglobin concentration of 10 g/dl, and the oxygen affinity, P50, is regulated
      to 32 Torr. In this study the authors examined the oxygen transporting capability
      of HbV in vivo, by performing exchange transfusions in rats. Exchange transfusion
      (90% of the estimated circulatory volume) with HbV suspended in 5% albumin
      (containing 160 mEq/L, sodium and 107 mEq/L, chloride) was carried out in male
      Wistar rats. Mean arterial pressure and heart rate were monitored through the
      arterial catheter. Arterial blood samples for gas analyses were also obtained
      from the arterial catheter. Abdominal aortic blood flow was measured by an
      ultrasonic pulsed Doppler flowmeter as an indicator of cardiac output. The oxygen
      tension of blood withdrawn from the right atrium was measured as an indicator of
      mixed venous oxygen tension. These values were employed to calculate oxygen
      delivery and consumption. Renal cortical and skeletal muscle tissue oxygen
      tensions were monitored as indicators of tissue perfusion. Five percent albumin
      and washed rat red blood cells suspended in 5% albumin containing 10 g/dl of
      hemoglobin; were employed as controls. At the completion of a 90% exchange
      transfusion, renal cortical and skeletal muscle tissue oxygen tensions, along
      with oxygen delivery and consumption, were sustained almost equally well with the
      HbV suspension compared to the washed rat red blood cell suspension, but declined
      significantly with the albumin suspension. The results indicate that the oxygen
      transporting capability of HbV was almost equivalent to that of rat red blood
      cells.

PMID- 9242944
TI  - Increased urea kinetic modeling volume. Possible mechanisms and its significance.
AB  - The presence of access recirculation reduces delivered urea clearance and
      produces an increased volume/weight (V/M) ratio in three-point kinetic modeling.
      We measured R in 20 patients receiving conventional hemodialysis and correlated
      results with normalized intra-access venous pressure (PIA) and with angiographic
      or color-flow Doppler studies. Twenty patients were equally divided into those
      with and without persistently elevated modeled V/W ratios (0.64 vs 0.53), and
      subdivided into those with native and synthetic bridge graft accesses. Kinetic
      modeling parameters (Kt/V) and P1A did not differ between the two V/W groups.
      Modeled volume was quite accurately predicted by the equations in the normal
      group but deviated by 7.3 +/- 2.1 L in the high V/W ratio group. Three of 10
      native and 4 of 10 graft accesses had trivial and hemodynamically insignificant
      abnormalities by color-flow Doppler or angiography. Recirculation was independent
      of V/W group and when measured by the slow flow/clamp technique was negligible (<
      2.0%). Access flow always exceeded prescribed dialyzer blood flow by more than
      300 ml/ min. Therefore, access recirculation was unlikely. In many of the high
      V/W patients, alternative explanations for falsely high modeled volume were found
      on follow-up modeling. Only one patient appeared to have a true high volume. The
      authors conclude that high urea volumes during kinetic modeling are unlikely to
      occur from access recirculation, but arise from other factors affecting the
      delivered urea clearance.

PMID- 9242945
TI  - Survival for up to six months in calves supported with an implantable axial flow
      ventricular assist device.
AB  - This paper summarizes the authors' in vivo experience to date with an implantable
      axial flow blood pump designed for long-term ventricular support. This small,
      valveless pump with blood-lubricated bearings has been implanted in six calves
      (83 +/- 6 kg) as a left ventricular assist device (LVAS). The left ventricle and
      descending thoracic aorta were cannulated by left thoracotomy, and the pump was
      placed in a subcutaneous pocket below the costal margin. Animals remained
      hemodynamically stable throughout the course of support during partial left
      ventricular bypass. Five animals were killed after 15, 27, 52, 57, and 181 days.
      The longest survivor (181 days) demonstrated normal pump function at the time
      death. Pump speed was maintained at 10,100 +/- 100 rpm, with an average pump flow
      rate of 4.9 +/- 0.5 L/min under resting physiologic conditions. Average plasma
      free hemoglobin was 17.4 +/- 7.5 mg/dl. Renal, hepatic, and hematologic indices
      remained within physiologic range in all of these animals, except during the
      immediate postoperative period. Histopathologic analyses of major organs after
      death revealed small renal cortical infarcts in five of six animals; the
      remaining organs were normal. These animal studies support the feasibility of
      this small implanted axial flow pump for long-term ventricular assistance.

PMID- 9242946
TI  - Compact compliance chamber design for the study of cardiac performance in
      microgravity.
AB  - A need was identified for a Mock Circulation System (MCS) of small size and
      weight that could function in a microgravity environment for the investigation of
      cardiovascular response to the weightlessness of space flight. Part of the MCS
      development involved the redesign of the compliance chamber from a Penn State MCS
      using a coil spring instead of the leaf spring system employed in the Penn State
      system. The new compliance chambers achieve a weight reduction of 47% and a
      volume reduction of 64% over the original Penn State design. Testing showed the
      coil spring compliance chambers retained physiologic characteristics and
      adjustability by using coil springs of various stiffness, and functioned
      equivalently to the original Penn State design.

PMID- 9242948
TI  - Numerical model and experimental investigation of blood flow through a
      bifurcation. Interaction between an artery and a small prosthesis.
AB  - The use of prosthetic vascular grafts as bypass to arteries of small diameter (<
      5 mm) often is thwarted by occlusion after months of apparently normal function.
      This work presents a numeric simulation of the flow through a distal anastomosis.
      A finite element method has been applied, providing information on the velocity
      field, streamlines, wall shear stresses, and vorticity in the different
      geometries. The study illustrates the dependence of the flow pattern and wall
      shear stress distribution upon Reynolds number, and the results show high shear
      stresses, approximately 3-5 times larger than normal, acting on the vessel wall
      at the branching point for the small diameter branch.

PMID- 9242947
TI  - Cannulation of the aortic branches using ultrasound guidance. An animal study.
AB  - Catheter placement by ultrasound may reduce radiation, improve positioning, and
      allow the use of echo contrast agents for diagnostic and therapeutic procedures.
      To evaluate its utility in the peripheral and coronary vascular beds, a preshaped
      20 MHz Doppler catheter was inserted into the femoral artery for renal artery, or
      into the right carotid artery for left coronary artery cannulation in five dogs.
      Ultrasonic imaging of the vascular structure and catheter was provided by either
      transabdominal or transesophageal ultrasound. Using Doppler waveform polarity for
      retrograde guidance, the catheter was advanced to the region of the left renal or
      left coronary ostia. Ultrasonic emissions from the Doppler catheter were
      identified by color Doppler mode of the ultrasound machine and allowed the
      catheter tip to be identified within the beam width of the scanning transducer,
      providing the depth dimension. In the two animals in which left renal artery
      cannulation was attempted, the catheter was successfully manipulated into the
      ostium. In two of the three animals in which left coronary artery cannulation was
      attempted, the catheter was successfully manipulated into the ostium, followed by
      saline contrast injections revealing myocardial perfusion. In addition, in one
      animal, a Doppler flow wire was identified as it was advanced into the mid
      circumflex coronary. In conclusion, ultrasonically guided cannulation of aortic
      branches may be possible without x-ray, and this technique may lead to further
      use of ultrasound in diagnostic and therapeutic procedures.

PMID- 9242949
TI  - Video assisted thoracoscopic and cardioscopic radiofrequency Maze ablation.
AB  - The authors examined the feasibility of transthoracic radio frequency Maze
      ablation of atrial fibrillation using video assisted thoracoscopy and cardioscopy
      in the experimental setting of a beating porcine heart. In six pigs under general
      anesthesia, the left atrium was viewed using a video assisted thoracoscopy system
      (VATS), and radiofrequency linear ablation of the left atrial wall was carried
      out using a radiofrequency ablation catheter (HAT200S:OSYPKA) inserted through a
      trocar port. The right atrium was also ablated in the same manner under VATS. In
      six other pigs, intravenous radiofrequency ablation by cardioscopic catheter
      device was carried out. Atrial fibrillation was provoked by acetylcholine
      injection plus rapid atrial pacing. The thoracoscopic visual field created for
      radiofrequency catheter ablation from a transthoracic approach and the
      cardioscopic visual field from an intravenous approach were sufficient, and safe
      positioning of the ablation catheter device on the atrial epicardium and
      endocardium, which enabled linear ablation of the atrium, was obtained. The
      Optimal setting for ablation was 70-80 degrees C/ 30 sec duration per each
      ablation. This process was monitored and documented by a video system through the
      thoracoscope and cardioscope, and results were confirmed by postmortem
      macrohistologic examination. In conclusion, the authors' results suggest the
      potential usefulness of the combination of transthoracic radiofrequency catheter
      ablation with video assisted thoracoscopic and cardioscopic linear ablation of
      atrial fibrillation, and the possibility that use of this system might eliminate
      the need for open heart Maze surgery.

PMID- 9242950
TI  - Cardiomyoplasty. Latissimus dorsi muscle function and blood flow during
      isolation.
AB  - Cardiomyoplasty is a new surgical treatment for heart failure in which skeletal
      muscle assists the heart. However, for the first 2 weeks postoperatively, the
      latissimus dorsi muscle (LDM) remains unstimulated, and during the next 2 weeks,
      the LDM is stimulated with only one pulse every other heart beat. Thus, for the
      initial 4 postoperative weeks, minimal systolic assistance is provided. The
      present study determined if the LDM is capable of providing early assistance.
      Cardiomyoplasty surgery involves severing the perforating intercostal arteries to
      the LDM, detaching the LDM from its distal insertion, and wrapping it around the
      heart. At each of these steps, we measured LDM force development, shortening, and
      blood flow in six dogs. At control, LDM shortening, work, and power decreased
      during a 2 min fatigue test: fatigue indices (final/ initial value) for
      shortening, work, and power were 47.6 +/- 6.9%, 47.5 +/- 7.1%, and 46.9 +/- 6.6%,
      respectively. Blood flow increased in the proximal (P), mid (M), and distal (D)
      LDM during the fatigue test. After partial vascular isolation, initial
      shortening, work, and power decreased by 29.4%, 32.5%, and 31.7% from their
      respective control values. During the fatigue test, fatigue indices for
      shortening, work, and power were 24.7 +/- 3.3%, 19.5 +/- 4.6%, and 22.2 +/- 4.7%,
      respectively, all significantly (p < 0.05) less than control values. Resting
      blood flows were unaltered. During exercise, flow to the P increased, whereas
      flow did not increase in M (p < 0.05). Loss of LDM function was most apparent
      after mobilizing and reattaching the muscle. Initial shortening, work, and power
      significantly decreased (p < 0.05) by 74.1%, 76.8%, and 74.4%, from their
      respective control values. During a fatigue test, final values for shortening,
      work, and power were all near zero. Resting blood flow decreased in the M and D
      (p < 0.05) and, during exercise, blood flow increased only in P. Thus, LDM
      function was severely depressed during the isolation procedure. This functional
      loss is associated with inadequate blood flow responses. Therefore,
      preconditioning and/or revascularization is needed if the LDM is to provide
      cardiac assistance shortly after cardiomyoplasty surgery.

PMID- 9242951
TI  - Monitoring and regulating latissimus dorsi muscle performance for circulatory
      assist.
AB  - The purposes of this study were monitoring and regulating latissimus dorsi muscle
      (LDM) performance with muscle internal pressure and thickness, and with burst
      stimulation parameters, respectively. The unconditioned LDM flap of a pig was
      connected to a measurement system to examine force and contraction length.
      Internal pressure was measured using a catheter pressure transducer with a fluid
      filled balloon inserted into the muscle, and correlated linearly with force
      during both contraction and relaxation. During contraction, thickness change
      correlated linearly with contraction length and the area enclosed within an
      internal pressure-thickness curve, and the X-axis was correlated linearly with
      muscle work. Stroke work increased incrementally according to the pulse width up
      to 6.72 msec or burst rate up to 120 Hz, and then plateaued at 240 Hz. The
      authors conclude that muscle work during contraction could be monitored with
      internal pressure and thickness, and that stroke work could be regulated with
      pulse width or burst rate.

PMID- 9242952
TI  - Effects of free latissimus dorsi dynamic cardiomyoplasty on left ventricular
      function.
AB  - In their experimental approach to dynamic cardiomyoplasty (DCMP), the authors
      hypothesized that a wrapping method using the proximal part of a free latissimus
      dorsi muscle (LDM) graft might augment ventricular contractility more than the
      classic Carpentier's wrapping method. The authors divided 12 mongrel dogs into a
      pedicled LDM graft group (Group 1, n = 6) and a free LDM graft group (Group 2, n
      = 6) to evaluate the properties of the different wrapping methods. To evaluate
      the effect of DCMP on left ventricular systolic and diastolic function, the
      authors used precise indicators that minimize the influences of load conditions.
      The slope of the linear preload recruitable stroke work relationship (Mw) and an
      X-intercept (Vo) were utilized as the indicator of left ventricular systolic
      function. The constants of pressure decay (tau) and peak filling rate (PFR) were
      measured to determine diastolic function. All experimental animals were evaluated
      with the acute, non preconditioning model. Mw was significantly increased with
      LDM stimulation in both groups (postwrap non stimulation 59.1 +/- 6.3; postwrap
      stimulation 98.6 +/- 9.7 erg.cm-3. 10(3); p < 0.01 in Group 1, postwrap non
      stimulation 66 +/- 6.7; postwrap stimulation 155 +/- 15.7 erg.cm-3.10(3), p <
      0.001 in Group 2). Stimulated free LDM grafts significantly increased the Mw in
      comparison to pedicled grafts (p = 0.011). Vo was unchanged in both groups and
      there was no significant difference between the two groups. Tau increased after
      LDM wrap in both groups (p < 0.05), but there was no difference between the two
      groups (tau; prewrap 45.8 +/- 6.0; postwrap non stimulation 69.3 +/- 10.3;
      postwrap stimulation 72.3 +/- 13.9 msec in Group 1, prewrap 50.0 +/- 6.0; post
      wrap non stimulation 61.8 +/- 5.0; post wrap stimulation in 64.3 +/- 4.7 msec in
      Group 2). Peak filling rate was unchanged after LDM wrap in both groups. Free LDM
      grafts significantly increased left ventricular systolic function compared to the
      pedicled LDM. Although myocardial relaxation was impaired after LDM wrap in both
      groups, there was no difference between the two groups. The authors' results
      emphasize the explicit benefit of utilization of a free LDM graft in respect to
      left ventricular systolic function; the free LDM grafts have no gross detrimental
      effect on diastolic function when compared with a pedicle graft in the acute
      model.

PMID- 9242953
TI  - A novel implantable electromechanical ventricular assist device. First acute
      animal testing.
AB  - A novel ventricular assist device (HIA-EMLVAD-AT1, Helmholtz Institute Aachen
      Electromechanical Left Ventricular Assist Device-Animal Test Version 1), driven
      by a uniformly and unidirectionally rotating actuator and a patented
      hypocycloidic pusherplate displacement gear unit, was developed and tested in an
      acute animal experiment. The excellent free filling behavior of the pump chamber
      with a stroke volume of 65 ml is obtained by a 2:3 ejection-filling time
      relationship. The uniform motor rotation facilitates simple sensorless pre and
      afterload detection by motor current analysis. In contrast to common apical
      cannulation, the inlet cannula was placed via the left atrium through the mitral
      valve into the left ventricle. This connection mode is preferable for left
      ventricular recovery and preservation. Left atrial, left ventricular, and aortic
      pressure curves, as well as pulmonary artery flow data, were obtained. The data
      show very effective unloading of the natural ventricle and demonstrate the
      feasibility of this novel assist device. Directions for further improvement of
      technical features were also identified.

PMID- 9242954
TI  - Elimination of FK-506 by continuous hemodiafiltration in a liver transplant
      patient.
AB  - A liver transplant patient who developed renal failure postoperatively was
      treated using continuous hemodiafiltration (CHDF). Doses ranging from 0.01 to
      0.06 mg/kg/day of FK-506 had been administered intravenously. FK-506
      concentrations before and after the filter, and in the ultradiafiltrate were 45.3
      +/- 2.9, 56.0 +/- 5.3, and 9.1 +/- 3.1 ng/ml (mean, +/- S.D.), respectively. The
      filtration rate was 23.6 +/- 6.4%, and extracted FK-506 amounted to 522.0
      micrograms (11.3% of administered dose). A part of the FK-506 administered was
      eliminated through the filter during CHDF.

PMID- 9242955
TI  - Left ventricular assist device support of medically unresponsive pulmonary
      hypertension and aortic insufficiency.
AB  - Most centers consider medically unresponsive pulmonary hypertension an absolute
      contraindication to orthotopic cardiac transplantation because the alternative
      surgical therapy, heterotopic graft placement, is associated with decreased
      survival, although most patients normalize their pulmonary hemodynamics
      postoperatively. Orthotopic transplantation in patients with elevated, but
      responsive pulmonary pressures, also is associated with an increased operative
      mortality rate and decreased long-term survival. The authors present the case of
      a patient with medically unresponsive pulmonary hypertension who was mechanically
      supported in an effort to improve his orthotopic transplant candidacy and
      decrease his risk. After informed consent, a HeartMate left ventricular assist
      device (LVAD) was inserted and the pulmonary hemodynamic response was monitored.
      Immediately before LVAD insertion, the pulmonary artery pressure (PA) was 74/28
      mmHg with a transpulmonary gradient (TPG) of 28 mmHg, and a pulmonary vascular
      resistance (PVR) of 6.6 Wood units, despite prolonged dobutamine, milrinone, and
      prostaglandin E1 infusions. After 10 weeks of LVAD support, pressure and
      resistance improved; pulmonary artery pressure was 28/15 mmHg, transpulmonary
      gradient was 15 mmHg, and pulmonary vascular resistance was 2.8 Wood units. This
      patient subsequently underwent an uneventful orthotopic heart transplant. At 1
      year after transplantation, pulmonary artery hemodynamics were normal (PA 34/14
      mmHg, TPG at 8 mmHg, and PVR at 1.5 Wood units). The authors recommend the
      consideration of LVAD placement in patients with medically unresponsive pulmonary
      artery hypertension to assess PA responsiveness and improve the patient's
      orthotopic cardiac transplant candidacy and decrease the operative risk. However,
      several weeks may be needed for normalization of pressure and resistance.

PMID- 9242956
TI  - NIH Biomaterials and Medical Implant Science Coordinating Committee.

PMID- 9242957
TI  - Processes in atherogenesis: complement activation.
AB  - The complement system consists of a complex group of plasma proteins, which, on
      activation, lead to a cascade of interactions culminating in the production of a
      variety of pro-inflammatory molecules. The system also contains cellular
      receptors for complement fragments produced during activation and regulatory
      molecules. It is part of the innate immune system representing humoral defence,
      but in certain circumstances may itself contribute to disease. In the formation
      of atherosclerotic lesions, there are two outstanding cellular phenomena,
      monocyte recruitment, with subsequent development of lipid-filled foam cells and
      smooth muscle cell activation. Subendothelial deposition of low density
      lipoprotein appears to be an important stimulus in these events and substantial
      evidence suggests that complement activation may be a link between lipoprotein
      deposition and subsequent lesion development.

PMID- 9242958
TI  - Serotonin (5-hydroxytryptamine, 5-HT) enhances migration of rat aortic smooth
      muscle cells through 5-HT2 receptors.
AB  - The effects of serotonin on migration of cultured rat aortic smooth muscle cells
      (SMC) were studied to clarify the role of this substance in the pathogenesis of
      atherosclerosis. Serotonin alone did not stimulate SMC migration but stimulated
      it at physiological concentrations in the presence of other migration factors
      such as SMC-derived migration factor, platelet-derived migration factor and
      fibronectin. Checker-board analysis revealed that the serotonin effect was
      chemotactic. Moreover, serotonin effects were completely abolished by a selective
      inhibitor of the 5-HT2 receptor (MCI-9042), indicating that serotonin effects
      were mediated through the 5-HT2 receptor pathway. Finally, serotonin effects were
      also abolished by a phospholipase C inhibitor, U73122, suggesting that the 5-HT2
      receptor mediated signal of serotonin was transduced by PLC. The results suggest
      that platelet-derived serotonin plays some role in the SMC dominant neointima
      formation.

PMID- 9242959
TI  - Polymorphism of the angiotensin-converting enzyme (ACE) gene in patients with
      thrombotic brain infarction.
AB  - The relationship between cerebrovascular disease and an insertion/deletion (I/D)
      polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is
      still being debated. We examined its role as a risk factor in patients with
      thrombotic brain infarction. The association between ACE polymorphism and
      ischemic stroke was examined in 181 patients with thrombotic brain infarction and
      271 controls without strokes. The I/D polymorphism was examined using the
      polymerase chain reaction. Distributions of the ACE genotypes and alleles did not
      differ between the infarcted patients and the controls. Both distributions in
      patients with onset at age 60 years or younger were significantly higher than
      those in younger controls (genotype: chi 2 = 7.6, P = 0.02; allele: chi 2 = 5.6,
      P = 0.02). There were no significant differences in the distributions of ACE
      genotypes and alleles between the patients with lacunar infarcts and with
      cortical infarcts in all ages. There were also significant differences in the
      distribution of ACE genotypes and alleles between the younger and the elderly
      subgroup of patients with brain infarction (genotype: chi 2 = 12.9, P = 0.002;
      allele: chi 2 = 11.1, P = 0.0009). Furthermore, there was a significant decline
      in the frequency of the ACE D allele with increasing age in all patients with
      thrombotic brain infarction. These observations demonstrated a significant
      association between the ACE gene polymorphism and thrombotic brain infarction in
      patients age 60 years or younger in a Japanese population. Furthermore, there may
      be an association between the ACE D allele and mortality after cerebral
      infarction.

PMID- 9242960
TI  - von Willebrand factor and soluble E-selectin in the prediction of cardiovascular
      disease progression in hyperlipidaemia.
AB  - Two specific endothelial cell products, von Willebrand factor and soluble E
      selectin, were measured together with serum lipids, lipoprotein(a), systolic and
      diastolic blood pressure (SHP, DBP) in a follow up study of 162 patients
      attending a dedicated lipid clinic. Patients were further classified by the
      presence or absence of symptomatic vascular disease and smoking. After a mean of
      49 months, 45 patients experienced a cardiovascular event (fatal or nonfatal
      myocardial infarction, stroke, or arterial surgery) and 11 developed non
      cardiovascular diseases, including cancer. In univariate analysis, existing
      vascular disease (P < 0.01), increased levels of von Willebrand factor (P <
      0.0001) and low density lipoprotein cholesterol (P < 0.02), greater age (P <
      0.01), and lower levels of soluble E-selectin (P < 0.03) were all predictive of
      future vascular events. However, in multivariate analysis, only increased von
      Willebrand factor was predictive (P < 0.001). von Willebrand factor was also
      higher in patients who developed non-cardiovascular disease relative to those
      free of disease (P < 0.05). Our data support the hypothesis that increased levels
      of von Willebrand factor are an indicator of poor prognosis in patients with
      atherosclerosis or its risk factors.

PMID- 9242961
TI  - Increased J774 macrophage cytotoxicity of late postprandial triglyceride-rich
      lipoproteins from normolipidemic young men expressing an apolipoprotein epsilon 4
      allele.
AB  - It has been demonstrated that normolipidemic young men with apolipoprotein E4/3
      phenotype have a prolonged postprandial clearance of triglyceride-rich
      lipoproteins following a high-fat diet. In the present study, we isolated fasting
      and postprandial (3 and 8 h) lipoprotein fraction from normolipidemic young men
      with E3/3 and E4/3 phenotypes and examined the in vitro cytotoxicity of these
      lipoproteins towards J774 macrophages. 8 h E4/3 very low density lipoprotein
      (VLDL) were significantly more cytotoxic than either 8 h E3/3 VLDL or fasting and
      3 h E4/3 VLDL (lactate dehydrogenase (LDH) released: 161 +/- 21, 107 +/- 9, 88 +/
      16 and 101 +/- 12 I.U./l, respectively). Fasting E4/3 intermediate density
      lipoprotein (IDL) were also significantly more cytotoxic than either fasting E3/3
      IDL or 3 h and 8 h E4/3 IDL (LDH released: 105 +/- 23, 60 +/- 9, 37 +/- 5 and 53
      +/- 16 I.U./l, respectively), whereas either fasting or postprandial low density
      lipoprotein (LDL) and high density lipoprotein (HDL) samples did not show any
      difference in cytotoxicity between the two groups studied. 8 h E4/3 VLDL samples
      incubated with J774 macrophages had a lower esterified cholesterol (40 +/- 3
      versus 52 +/- 3 micrograms), and higher triglyceride (783 +/- 133 versus 418 +/-
      64 micrograms) and free fatty acid (FFA) (2.0 +/- 0.4 versus 0.9 +/- 0.1
      microgram) content than fasting E4/3 VLDL. The increased macrophage cytotoxicity
      of late postprandial triglyceride-rich lipoproteins seems to be related to the
      FFA content of E4/3 VLDL.

PMID- 9242962
TI  - Minimal oxidation and storage of low density lipoproteins result in an increased
      susceptibility to phospholipid hydrolysis by phospholipase A2.
AB  - In vitro-studies have shown that phospholipid hydrolysis of low density
      lipoproteins (LDL) by bee venom or porcine pancreatic phospholipase A2 (PLA2)
      leads to an increased uptake of these lipoproteins by macrophages transforming
      them into foam cells. Recently, a secretory phospholipase A2, group II, was
      detected in human atherosclerotic plaques. In order to investigate the role of
      this enzyme in the pathogenesis of atherosclerosis, a structurally identical
      human secretory PLA2 was purified from the medium of HepG2 cells stimulated with
      interleukin-6 and tumor necrosis factor-alpha. The activity of the purified
      enzyme towards the phospholipids of native and modified low density lipoproteins
      was compared with the activity towards Escherichia coli-membranes and other
      phospholipid substrates. Compared to E. coli-membranes, native LDL proved to be a
      poor substrate for group II PLA2. After mild oxidation induced by copper ions or
      by 2,2-azobis(2-amidinopropane) (AAPH), the susceptibility of LDL to phospholipid
      hydrolysis was found to be increased by 25 and 23%, respectively, whereas
      extensive copper-mediated oxidation caused a decreased hydrolysis. Aging of LDL
      at 6 degrees C for weeks or at 37 degrees C for hours resulted in an increase in
      PLA2-catalyzed phospholipid hydrolysis of up to 26-fold. LDL protected from
      oxidation by probucol during aging showed a lesser increase in susceptibility to
      phospholipid hydrolysis. Our results suggest that PLA2, group II, can increase
      the atherogenicity of LDL by its ability to hydrolyze the phospholipids of these
      lipoproteins, especially after modifications that are likely to occur in vivo.

PMID- 9242964
TI  - Antiatherogenic effects of long-term benfluorex treatment in male insulin
      resistant JCR:LA-cp rats.
AB  - The JCR:LA-corpulent rat is an animal model that, if homozygous for the cp gene
      (cp/cp), spontaneously exhibits obesity and a severe insulin resistance, with a
      resultant hyperinsulinemia and hypertriglyceridemia. The obese male rats show
      defective nitric oxide-mediated vascular relaxation, advanced atherosclerosis,
      and ischemic myocardial lesions. Benfluorex has both anorectic and metabolic
      effects that lower body weight and improve insulin sensitivity in obesity and
      type 2 diabetes. Male cp/cp rats that were treated with benfluorex (or pair-fed
      to the treated animals) from the time of weaning, at 3 weeks of age, showed a
      marked delay in the development of postprandial hyperinsulinemia. At 12 weeks of
      age benfluorex-treated cp/cp rats did not show the extreme insulin response to a
      test meal that was observed in untreated or pair-fed rats. Both benfluorex
      treated and pair-fed rats had a significant increase in sensitivity to
      acetylcholine-induced (nitric oxide-mediated) vascular relaxation. Corpulent male
      rats were also treated from 6 to 39 weeks of age with benfluorex in the feed at a
      dose of approximately 36 mg/kg/day at 12 weeks of age and decreasing to 23
      mg/kg/day at 39 weeks to determine the effects on cardiovascular outcomes. The
      rats showed a sustained decrease in food consumption and body weight, although
      they exhibited 50% of the excess body weight of the controls and were grossly
      obese. Both fasting insulin concentrations and the hyperplasia of the islets of
      Langerhans were decreased by approximately 50%. Serum triglyceride concentrations
      were decreased by 44%, and free cholesterol and cholesteryl esters by 30%. The
      severity of the atherosclerotic lesions on the aortic arch was decreased (P <
      0.05). There was also a decrease in the size of early ischemic myocardial lesions
      that are characterized by cell lysis and chronic inflammatory cell infiltration.
      Mature, scarred myocardial lesions were essentially absent in the hearts of 39
      week-old benfluorex-treated rats. Long-term major food restriction (18 g/day)
      decreased the body weights of obese rats to essentially those of lean control
      animals, with similar beneficial effects on the insulin resistance and
      hyperlipidemia. While myocardial lesion frequency was reduced in these much
      thinner animals, lesions remained and the apparent effect was not statistically
      significant. This evidence shows that the beneficial metabolic effects of
      benfluorex are associated with long-term effects on the vessel wall and delay the
      onset of insulin resistance and cardiovascular disease in an animal model.

PMID- 9242963
TI  - Stimulation of endothelial nitric oxide production by homocyst(e)ine.
AB  - Hyperhomocyst(e)inemia, characterized by accelerated atherosclerosis, is believed
      to induce endothelial cell injury and promote atherothrombosis by supporting the
      generation of hydrogen peroxide. Earlier observations in our laboratory
      demonstrated that in vitro nitrosation of homocyst(e)ine (HCY) prevents the
      generation of hydrogen peroxide. We, therefore, hypothesized that stimulating the
      production of nitric oxide (NO) by endothelial cells would detoxify HCY by
      forming the corresponding S-nitrosothiol, S-nitroso-homocysteine. In an attempt
      to prove this hypothesis, media containing 1 mM L-arginine, 1 microM bradykinin,
      a known NO agonist, and one of the biologically relevant thiols (HCY, cysteine,
      or glutathione) at concentrations of 0, 0.05, 0.5 and 5.0 mM were incubated with
      bovine aortic endothelial cells (BAEC) for 0.5, 1 and 4 h. S-nitrosothiol (RSNO)
      concentrations were measured by photolysis-chemiluminescence. Nitric oxide
      synthase (eNOS or isoform 3) activity and Nos 3 steady-state mRNA levels were
      determined by the conversion of [3H]L-arginine to [3H]L-citrulline and Northern
      analysis, respectively. Results demonstrate that increasing concentrations of
      HCY, and not cysteine or glutathione, in the presence of bradykinin at 0.5, 1,
      and 4 h led to significant (P < 0.05 by ANOVA) time- and dose-dependent increases
      in RSNO produced by BAEC. Cells exposed to 1 microM calcium ionophore A23187 in
      the presence of 5.0 mM HCY also produced a time-dependent increase in RSNO
      compared to control (P < 0.05 by ANOVA). In an attempt to determine if de novo
      synthesis was occurring, BAEC were treated with bradykinin following a 4 h
      pretreatment with HCY. Pretreatment with HCY followed by stimulation also led to
      a time- and dose-dependent increase in RSNO production (P < 0.05 by ANOVA). Using
      high performance liquid chromatography with electrochemical detection, S-nitroso
      homocysteine was identified following treatment of BAEC with HCY and bradykinin.
      The increase in RSNO production in the presence of bradykinin and HCY at 4 h
      occurred concomitantly with a 78% increase in eNOS activity and a 58% increase in
      steady-state Nos 3 mRNA, with no change in Nos 3 mRNA half-life, compared to
      control. A partial explanation for HCY's unique ability to support an increase in
      NO production was demonstrated by showing that the t1/2 of HCY in media was
      greater than that of cysteine or glutathione. These data show that, in the
      presence of an NO agonist, HCY increases RSNO production in a time- and dose
      dependent fashion that is reflected by an increase in eNOS activity and Nos 3
      transcription. These results suggest that stimulation of endogenous NO, or
      provision of an exogenous NO donor, may ameliorate endothelial cell injury and
      thereby decrease the atherothrombotic risk of hyperhomocyst(e)inemic states.

PMID- 9242965
TI  - Adenovirus-mediated gene transfer of basic fibroblast growth factor induces in
      vitro angiogenesis.
AB  - To investigate the possibility of adenovirus-mediated gene transfer in the
      treatment of vascular occlusive diseases, we constructed a replication-deficient
      recombinant adenovirus vector coding for human basic fibroblast growth factor
      (bFGF) and examined its effect on the proliferation and differentiation of
      vascular endothelial cells in vitro. Human umbilical vein endothelial cells
      (HUVECs) were successfully infected with high efficiency and expressed 18 kD
      protein which is immunoreactive to anti-bFGF monoclonal antibody. This protein
      was accumulated mainly in the nuclei of the cells, but was also detected in the
      culture medium although the complimentary DNA (cDNA) did not contain the
      classical secreting signal sequence. The proliferation assay of HUVECs infected
      with bFGF-expressing adenovirus revealed a significant increase in cell number
      over control. Infection with this virus also enhanced tubular formation of HUVECs
      on reconstituted basement membrane. Neovascularization and the formation of
      collateral vessels play important roles in minimizing tissue damage in ischemic
      disorders. These results imply that the use of bFGF-expressing recombinant
      adenovirus may be a suitable in vivo gene therapy for ischemic diseases.

PMID- 9242966
TI  - LDL from aerobically-trained subjects shows higher resistance to oxidative
      modification than LDL from sedentary subjects.
AB  - We studied the effect of regular intense aerobic exercise on the LDL
      susceptibility to oxidation and the electronegative LDL-proportion (LDL(-)). A
      group of 38 well-trained athletes was compared to a group of 38 age-BMI-matched
      sedentary individuals. Athletes showed higher concentration of total cholesterol
      (athletes 5.08 +/- 0.70 versus controls 4.65 +/- 0.75 mmol/l, P = 0.0229) and HDL
      cholesterol (athletes 1.72 +/- 0.47 versus controls 1.46 +/- 0.39 mmol/l, P =
      0.0068); total plasma triglyceride, LDL cholesterol and VLDL cholesterol did not
      differ between trained and untrained subjects. The susceptibility of LDL to
      oxidation, determined by conjugated dienes formation and expressed as lag phase,
      was lower in athletes than in sedentaries (trained subjects 47.0 +/- 5.6 versus
      sedentary subjects 41.9 +/- 5.0 min, P = 0.0002). LDL(-) was similar in both
      groups (athletes 10.32 +/- 4.70 versus controls 10.26 +/- 3.71%). The antioxidant
      content in total plasma and isolated LDL (alpha-tocopherol, retinol, lycopene,
      alpha-carotene and beta-carotene) was quantitated by HPLC in a subgroup of 32
      athletes and 32 control subjects. Athletes showed higher amounts of alpha
      tocopherol and retinol in plasma, but not in LDL. However, none of these
      antioxidants correlated with the lag phase time. Trained subjects showed lower
      prevalence of smoking. However, no differences were observed between smokers and
      non-smokers concerning lag phase. No significant difference between athletes and
      sedentaries concerning LDL density, or composition was observed. We conclude that
      LDL from trained subjects is more resistant to oxidative modification than LDL
      from sedentary subjects. This observation could not be attributed to conventional
      antioxidants as alpha-tocopherol and carotene content of LDL was unchanged in
      trained subjects. Thus, although none of the variables studied appear as a single
      predictor of the LDL susceptibility to oxidation, an additive effect of the
      antioxidant content, the presence of some undetermined co-antioxidant, HDL and/or
      smoking habits cannot be discarded as responsible for the increased resistance to
      oxidation of LDL in trained subjects.

PMID- 9242967
TI  - Haptoglobin polymorphism, a genetic risk factor in coronary artery bypass
      surgery.
AB  - Haptoglobin (Hp) 2-2 type has been associated with accumulation of
      atherosclerotic lesions in essential hypertension. The aim of this study was to
      investigate the relationship between Hp type and the extension of coronary
      lesions in 765 male patients who underwent coronary artery bypass grafting
      (CABG). In this group, relative Hp1 (0.418) and Hp2 (0.582) allele frequencies
      were comparable with those of the reference population. Candidate CABG patients
      with a Hp 2-2 type were overrepresented in the younger (< 45 years) age group (P
      < 0.05). Hp 2-2 patients needed more bypass grafts than Hp 1-1 patients (relative
      risk 1.92 95% C.I. 1.24-2.96). The Hp 2-2 type was overrepresented among victims
      of a previous acute myocardial infarction (P < 0.05) and among patients with a
      lower (< 45 years) age at infarction (P < 0.05). In patients who already
      underwent a previous CABG graft survival time was shortest in Hp 2-2 type (P <
      0.05). Patients with a Hp 2-2 type more likely develop atherosclerotic lesions
      despite comparable serum lipid concentrations.

PMID- 9242968
TI  - A dietary and behavioral intervention designed to lower coronary heart disease.
      Risk factors are unaffected by variation at the APOE gene locus.
AB  - Variation at the apolipoprotein E (APOE) gene locus has demonstrated a consistent
      impact on lipoprotein levels. APOE typing was performed for 488 healthy,
      caucasian, premenopausal women participating in the Women's Healthy Lifestyle
      Project (WHLP) aimed at reducing total fat, saturated fat and cholesterol intake
      and promoting physical activity. Women in both the intervention and control
      groups were included in the trial. The purpose of the present study was to
      determine whether the magnitude of the changes in total cholesterol (Tc), low
      density lipoprotein cholesterol (LDLc) and high density lipoprotein cholesterol
      (HDLc) due to the dietary intervention were dependent on the variation in APOE.
      Weight, body mass index (BMI), and lipoprotein levels were measured at baseline
      and at a 6 month follow-up. ANOVA was used to determine whether the change in Tc
      and LDLc was dependent on dietary intervention and variation at APOE levels. The
      levels of Tc and LDLc were higher in women with the APOE*4 genotype. There were
      no statistically significant effects of APOE genotype and changes in Tc and LDLc
      (P > 0.1). Adjusted Tc and LDLc changes were comparable in the 3 APOE subgroups
      (Tc = -14.3, -12.9 and -11.7 mg/dl; LDLc = -12.1, -10.7 and -10.7 mg/dl,
      respectively as above). In conclusion, the genetic (APOE) background of
      premenopausal women in this study did not have a significant effect on their
      response to dietary intervention.

PMID- 9242969
TI  - Clinical characteristics of double heterozygotes with familial
      hypercholesterolemia and cholesteryl ester transfer protein deficiency.
AB  - Coronary heart disease (CHD) in familial hypercholesterolemia (FH) may be
      modified by genetic and/or environmental factors. We described the effect of the
      cholesteryl ester transfer protein (CETP) gene on CHD in heterozygous FH caused
      by low density lipoprotein receptor (LDL-R) gene mutation. In 288 unrelated
      Japanese subjects with heterozygous FH, the allele frequency of an intron 14
      G(+1)-to-A mutation (Int14 A) and a missense mutation in exon 15 (Asp442 to Gly,
      D442G) was 0.3 and 3.0%, respectively. HDL-C levels (1.55 +/- 0.08 mmol/l) in FH
      patients with heterozygous CETP deficiency were higher than those (1.19 +/- 0.08
      mmol/l) in FH without CETP deficiency (P < 0.03), while LDL-C levels in FH with
      CETP deficiency were moderately reduced. However, two FH patients with CETP
      deficiency suffered myocardial infarction, and six patients had effort angina
      pectoris and/or coronary atherosclerosis. No difference in the score of coronary
      stenosis index (CSI) was found in FH with/without CETP deficiency, although CSI
      was inversely correlated with HDL-C levels (P < 0.05). Thus, the effect of
      increased HDL-C levels caused by partial deficiency of CETP is insufficient to
      prevent CHD in FH.

PMID- 9242970
TI  - Serum leptin levels are independently correlated with two measures of HDL.
AB  - Leptin is the peptide product of the OB gene, which is associated with obesity in
      some strains of mice. Because dyslipidemias are frequently associated with
      obesity, we have begun to characterize the pathways connecting these related
      traits. In this investigation we tested for correlation of HDL phenotype measures
      with leptin concentrations using data from 1159 participants in the San Antonio
      Family Heart Study, a study of risk factors for cardiovascular disease in Mexican
      Americans living in and around San Antonio, Texas. In a subset of 288 unrelated
      individuals, we tested for correlation of leptin with nine different measures of
      HDL phenotype and found that only three were significantly related. However,
      stepwise regression analysis suggested that only two measures, HDL triglyceride
      concentrations (HDL-TG) and the proportion of apo A-I on HDL particles larger
      than HDL3 (Large HDL-apo A-I), were independently correlated with leptin. Because
      obesity and HDL phenotypes are both under strong genetic control, we conducted a
      trivariate genetic analysis, using the entire data set, to test the hypothesis
      that the phenotypic correlations were due to the effects of shared genes (i.e.,
      pleiotropy). Heritabilities for the three traits were estimated to be 0.47 for
      leptin, 0.46 for HDL-TG, and 0.46 for Large HDL-apo A-I. Results from the genetic
      analyses revealed that the phenotypic correlation of leptin with HDL-TG was
      nongenetic (i.e., shared environment), while the phenotypic correlation with
      Large HDL-apo A-I was due to pleiotropy (i.e., shared genes). These results
      confirmed the result derived from the subset of unrelated individuals that the
      two measures of HDL are independently correlated with leptin. To our knowledge,
      this is the first report of a relationship between leptin and any aspect of
      lipoprotein phenotype. A better understanding of the genes responsible for this
      relationship may provide a molecular explanation for the aggregation of
      atherogenic phenotypes, such as diabetes, obesity, and dyslipoproteinemia.

PMID- 9242971
TI  - New indices to classify location, severity and progression of calcific lesions in
      the abdominal aorta: a 25-year follow-up study.
AB  - The purpose of the present study was to assess the location, severity and
      progression of radiopaque lumbar aortic calcifications and to evaluate the
      utility of summary scores of lumbar calcification in a population-based cohort.
      Lateral lumbar films, obtained in 617 Framingham heart study participants, were
      analysed for the presence of abdominal aortic wall calcification in the region
      corresponding to the first through fourth lumbar vertebrae. The severity of the
      anterior and posterior aortic calcification were graded individually on a 0-3
      scale for each lumbar segment and the results were summarized to develop four
      different composite scores: (1) affected segments score (range 0-4); (2) anterior
      and posterior affected score (range 0-8); and (3) antero-posterior severity score
      (range 0-24). The prevalence of aortic calcification was 37% in men and 27% in
      women at baseline and 86% in both genders at the follow-up exam 25 years later.
      During the follow-up interval, the mean of the affected segments score increased
      from 0.7 in men (0.5 in women) to 2.7 (2.8 in women), the mean of the anterior
      and posterior affected score from 1.2 (0.8 in women) (P = 0.012 for difference
      between genders) and the mean of the antero-posterior severity score increased
      from 1.5 (1.3 in women) to 9.3 (10.3 in women). The antero-posterior severity
      score offered a slight advantage over other composite scores and had the highest
      inter-rater intra-class correlations. In summary, lumbar aortic calcification can
      be graded and composite summary scores are reproducible. This technique appears
      to provide a simple, low cost assessment of subclinical vascular disease.

PMID- 9242972
TI  - The cholesterol-raising diterpenes from coffee beans increase serum lipid
      transfer protein activity levels in humans.
AB  - Cafestol and kahweol-diterpenes present in unfiltered coffee-strongly raise serum
      VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The
      mechanism of action is unknown. We determined whether the coffee diterpenes may
      affect lipoprotein metabolism via effects on lipid transfer proteins and
      lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over
      study with 10 healthy male volunteers. Either cafestol (61-64 mg/day) or a
      mixture of cafestol (60 mg/day) and kahweol (48-54 mg/day) was given for 28 days.
      Serum activity levels of cholesterylester transfer protein, phospholipid transfer
      protein and lecithin:cholesterol acyltransferase were measured using exogenous
      substrate assays. Relative to baseline values, cafestol raised the mean (+/-
      S.D.) activity of cholesterylester transfer protein by 18 +/- 12% and of
      phospholipid transfer protein by 21 +/- 14% (both P < 0.001). Relative to
      cafestol alone, kahweol had no significant additional effects
      Lecithin:cholesterol acyltransferase activity was reduced by 11 +/- 12% by
      cafestol plus kahweol (P = 0.02). It is concluded that the effects of coffee
      diterpenes on plasma lipoproteins may be connected with changes in serum activity
      levels of lipid transfer proteins.

PMID- 9242974
TI  - The economic impact on families of children's participation in junior sport.
AB  - The study investigated the socio-economic consequences for families of
      participation in junior sport. Two hundred and twenty families in Queensland and
      Victoria were surveyed from the sports of cricket, Australian football,
      gymnastics, hockey, netball and tennis and twenty seven of these interviewed. The
      study showed that parents make a substantial contribution in terms of financial
      support to their children's participation in junior sport. Each of the sports
      mode different financial demands on families depending on the yearly cycle of
      training and competition, distance from facilities and coaching, costs associated
      with coaching, equipment and uniforms, and representative level. It is concluded
      that family income and structure are the key factors in determining the
      likelihood of a child's involvement in junior sport, and that for many Australian
      children, financial factors may be barriers to their participation in junior
      sport.

PMID- 9242973
TI  - Importance of apo E2 heterozygosity, insulin, and hypertriglyceridemia for very
      low density lipoproteins.

PMID- 9242975
TI  - Perspectives of sport physiotherapists on the frequency and significance of
      psychological factors in professional practice: implications for curriculum
      design in professional training.
AB  - A two-part study was conducted with sport physiotherapists to examine their
      perceptions of both frequency and significance of emotions and behaviours
      displayed by injured athletes during treatment, and the importance of
      psychological skills in rehabilitation. A questionnaire, developed from a
      preliminary study (Part 1) with experienced sport physiotherapists (N = 10), was
      mailed to 500 sport physiotherapists in Australia, New Zealand and Canada (Part
      2). Responses from Australian (N = 147), New Zealand (N = 65) and Canadian (N =
      45) subjects suggested that: (i) anxiety and frustration is experienced
      frequently by injured athletes, and non-compliance to the rehabilitation program
      is a significant problem preventing effective recovery and rehabilitation; (ii)
      psychological skills training and learning to deal with psychological responses
      to injury would facilitate more effective treatment; and (iii) athlete self
      presentation styles influence the support and attention received from
      physiotherapists. Results are discussed in relation to previous research and
      recommendations for improving both the art (applied skills) and science
      (theoretical content) of professional training programs for sport
      physiotherapists are provided.

PMID- 9242976
TI  - Perceived uncertainty of outcome as a contributing factor in competitive state
      anxiety.
AB  - The Martens, Vealey, and Burton (1990) model of competitive anxiety contains
      perceived uncertainty, perceived importance, and competitive trait anxiety (A
      trait) as key determinants affecting a person's perception of threat and
      competitive state anxiety (A-state). This experiment tested perceived uncertainty
      of outcome and A-trait influences on A-state. Club level golfers (N = 72) were
      assigned to either a low uncertainty condition (LU) or a high uncertainty (HU)
      condition. In this experiment participants were matched and competed for 12 golf
      balls in a modified chipping competition. Participants also completed the
      Competitive State Anxiety Inventory -2 and the Match Orientation Questionnaire (a
      measure of perceived uncertainty) prior to, and during breaks in the competition.
      Players alternated in taking four rounds of eight shots from a zone marked
      approximately 30 metres from the hole. A series of tests did not support the
      manipulation of uncertainty. This was probably due to likely losers and likely
      winners not experiencing similar levels of A-state, as Martens et al. assume.
      Recoding the uncertainty data to reflect levels of confidence, and entering
      confidence and A-trait into multiple regression equations resulted in these two
      variables accounting for between 15% and 23% of the A-state variance at different
      stages of the competition. Recommendations for future research, and possible
      revisions of the model in light of the present findings are discussed.

PMID- 9242978
TI  - Sampling arterialised-venous blood from a dorsal-hand vein during exercise
      without compromising a competitive cycling position.
AB  - The arterialisation of dorsal-hand venous blood, using a new hand-heating sleeve
      that did not disrupt a normal competitive cycling position, was evaluated in 10
      male cyclists. Hand-heating was achieved by pumping heated water through a
      rubberised panel which rested against the dorsal and ventral surfaces of the
      right hand. Subjects were cannulated near the dorsal venous arch in both hands
      and blood samples were collected simultaneously at rest under normothermic
      conditions for 9 subjects, and at rest and after 10, 20 and 30 min of exercise at
      50% of the anaerobic threshold for 10 subjects, when only the right hand was
      heated. No bilateral differences for PO2, PCO2 or pH were observed between
      normothermic hands at rest (p > 0.05). The heating sleeve increased the hand
      temperature (p < 0.05) and produced a significant (p < 0.05) arterialisation of
      blood samples collected from a dorsal-hand vein, compared to values observed in
      the non-heated hand, at rest and during 30 min of exercise. PO2 and pH were about
      10 mm Hg and 0.01 units higher, and PCO2 was about 1.5 mm Hg lower, for samples
      collected from the heated compared to the non-heated hand. This new method of
      hand-heating was effective in arterialising venous blood and minimised the need
      for variation to a normal, competitive cycling position.

PMID- 9242977
TI  - Accuracy of two pulse oximeters during maximal cycling exercise.
AB  - This study compared the measurement of oxygen saturation of haemoglobin (SaO2) by
      two pulse oximeters (Ohmeda Biox 3700e and Criticare 504 USP) with the
      measurement of SaO2 in arterial blood samples by CO-oximetry. Unlike many
      previous validation studies, arterial blood was sampled in ground glass rather
      than plastic syringes. Twenty men, 11 well-trained cyclists (mean +/- SE, age =
      23.3 +/- 1.5 years, mass = 71.4 +/- 1.1 kg VO2max = 77 +/- 1 ml.kg1.min-1) and 9
      relatively untrained subjects (age = 27.1 +/- 2.8 years, mass = 78.1 +/- 2.2 kg
      VO2max = 51 +/- 3 ml.kg 1.min-1) performed two maximal cycle ergometer tests each
      in an hypobaric chamber. The tests were at 745 mm Hg or 695 mm Hg with
      simultaneous measurement of SaO2 by the pulse oximeters and the CO-oximeter at
      rest, minute 7 of exercise and at VO2max. The best correlations, to the Co
      oximeter measurement (SCO-OXO2) were found when all data from rest and exercise
      were combined (Criticare: r = 0.94; Ohmeda: r = 0.91). The bias measurements
      showed the Ohmeda underestimated SCO-OXO2 at all levels (mean = -2.5 +/- 1.9%)
      and the Criticare overestimated SCO-OXO2 at all levels, although to a lesser
      degree (mean = 0.9 +/- 1.5%). In conclusion, these results highlight the need for
      validation of individual pulse oximeters and that the effect of dyshaemoglobins
      must also be considered.

PMID- 9242979
TI  - Psychophysiological stress in elite golfers during practice and competition.
AB  - This study examined self-reported state anxiety (cognitive anxiety, somatic
      anxiety and self-confidence) measured by the Competitive State Anxiety Inventory
      2 (CSAI-2; Martens, Vealey, Bump, & Smith, 1990) and physiological responses
      (salivary cortisol concentration and heart rate) in elite golfers prior to,
      during and on completion of a tournament and practice round. The relationships
      between psychophysiological variables were investigated by comparing
      physiological and psychological responses during competition and practice to each
      other, and to performance. Performance was determined for each player as the
      difference between 18 hole score and handicap. Fifteen male Professional Golfing
      Association (PGA) trainees (aged 21-25 years) competed in a PGA sanctioned
      tournament and a practice round on the same, or similar golf course. Players
      completed the CSAI-2 and collected saliva for cortisol analysis on four
      occasions: prior to tee off, and after completing holes 6, 12 and 18. Cortisol
      concentration was corrected for circadian variations in cortisol secretion, using
      baseline cortisol measures. Within-subject analysis revealed elite golfers
      experienced elevated cortisol, heart rate, cognitive and somatic anxiety, and
      lower self-confidence during competition compared to practice. For both game
      conditions, the highest cortisol response was measured prior to the commencement
      of play, whilst state anxiety measures did not change significantly during the
      golf rounds. Univariate and multivariate analyses failed to reveal significant
      correlations between the psychophysiological variables and golf performance. In
      conclusion, competition and practice were clearly discriminated by the
      psychophysiological variables, but none of these predicted performance.

PMID- 9242980
TI  - An investigation into the ability of C-terminal homologues of Escherichia coli
      low molecular mass penicillin-binding proteins 4, 5 and 6 to undergo membrane
      interaction.
AB  - The Escherichia coli low molecular mass penicillin-binding proteins (PBP4, PBP5
      and PBP6) are a group of penicillin-sensitive enzymes involved in the final
      stages of cell wall assembly. It has been suggested that these proteins may
      interact with the periplasmic face of the inner membrane via C-terminal
      amphiphilic alpha-helices. Theoretical analysis has predicted that these C
      terminal helical regions may be membrane interactive. We have tested this
      hypothesis by assaying PBP C-terminal homologues (P4, P5 and P6) for haemolytic
      activity. Our results show that the PBP5 and PBP6 C-terminal homologues readily
      lyse sheep erythrocytes in a pH-dependent manner with LD50's of 3.5 x 10(-6) M
      and 6.8 x 10(-7) M respectively at pH 7. These results appear to support the
      present model for the membrane anchoring of PBP5 and PBP6. The PBP4 C-terminal
      homologue shows no evidence of haemolytic activity which could imply a different
      means of membrane association for PBP4.

PMID- 9242981
TI  - NAD+ loading of mammalian cells by electrotransfection leads to increased
      poly(ADP-ribosyl)ation capacity.
AB  - Many cellular enzymes use NAD+ as coenzyme or substrate, depending on the nature
      of the enzymatic reaction. Under certain conditions the cellular NAD+
      concentration may become rate-limiting for such enzymes. For instance, when
      eucaryotic cells are exposed to high concentrations of DNA-damaging agents, the
      resulting DNA strand breaks may stimulate the nuclear enzyme poly(ADP-ribose)
      polymerase (PARP) to such an extent that the cellular pool of NAD+, which is the
      substrate for this enzyme, is severely depleted, possibly leading to acute cell
      death. Here we show that NAD+ concentrations in CV-1 monkey and CO60 hamster
      cells can be raised 3- to 4-fold by electrotransfection of NAD+. This additional
      NAD+ is indeed available for PARP to synthesize higher-than-normal amounts of
      poly(ADP-ribose) after treatment with the alkylating agent N-methyl-N'-nitro-N
      nitrosoguanidine. NAD+ loading of cells by electrotransfection may be useful also
      for the study of other cellular reactions in which NAD+ is involved.

PMID- 9242982
TI  - Effect of pH on the role of Mg2+ and Mn2+ on Phycomyces isocitrate lyase
      kinetics.
AB  - Mg2+ and Mn2+ function with the same partial mixed-type activation/inhibition
      mechanism, in which the metal isocitrate complex is the true substrate of
      Phycomyces isocitrate lyase. Binding of Mg2+ or Mn2+ to the activation site
      normally contributes significantly to the mechanism of catalysis. Whereas both
      ions activate catalysis at pH 7.3, at pH 8.5, Mg2+ ions behaved as inhibitors
      (beta < 1) and Mn2+ ions continued to function as activators. The binding of Mg2+
      or Mn2+ to the activator site is virtually independent of the pH value. The
      affinity of the non-activated form of the enzyme for the Mg(2+)-isocitrate
      complex decreased (Ksa increased 20-fold) as pH was raised, but for Mn2+ ions the
      affinity of the activated enzyme for the Mn(2+)-isocitrate complex decreased 86
      fold. The ion moiety of the metal-ion-isocitrate complex appears to be involved
      in the formation of the active enzyme-substrate complex from the non-activated
      enzyme.

PMID- 9242983
TI  - S6 ribosomal protein phosphorylation and translation of stored mRNA in maize.
AB  - This article focuses on the effect that S6 ribosomal protein phosphorylation
      might have in regulating mRNA translation. Maize axes of either 4 or 14 h of
      germination were pulse-labelled for 1 h with [32P]-orthophosphate. Analysis of
      their ribosomal proteins by gel electrophoresis and autoradiography showed
      distinctive levels of S6 ribosomal protein phosphorylation for both ribosomal
      sets. Axes at these two stages of germination were treated with alpha-amanitin to
      ensure transcription inhibition and pulse-labelling with [35S]-methionine. The
      [35S]-proteins, resulting from stored mRNA translation, when analysed by 2-D-gel
      electrophoresis and fluorography revealed distinctive [35S]-protein patterns. In
      vitro translation of stored mRNA on ribosomes from either 4 or 14 h germinated
      maize axes produced different [35S]-protein patterns. Further, addition of
      7methyl-GTP-Sepharose to the translation system showed differential cap-dependent
      protein synthesis inhibition depending on the set of ribosomes tested. It is
      concluded that translation of stored mRNA in germinating maize axes is at least
      partially regulated by a mechanism that involves S6 ribosomal protein
      phosphorylation.

PMID- 9242984
TI  - Organization of the Thermus thermophilus nusA/infB operon and overexpression of
      the infB gene in Escherichia coli.
AB  - The structural gene for translation initiation factor IF2 from Thermus
      thermophilus was identified on the basis of the N-terminal amino acid sequence of
      intact T thermophilus IF2 and an internal 25 kDa IF2 fragment. A total of 5135 bp
      was cloned and sequenced, comprising the open reading frames for p15A, NusA,
      p10A, IF2, p10B and SecD, which may form an operon. There are pronounced
      similarities between the operon arrangement and primary sequence of the T
      thermophilus genes and proteins, respectively, and their counterparts from other
      organisms. The T thermophilus infB gene was expressed to a high level in E coli.
      Four hundred milligrams of homogenous T thermophilus IF2 were prepared from 60 g
      of overproducing cells.

PMID- 9242985
TI  - Evidence for a specific interaction of vitronectin with arginine: effects of
      reducing agents on the expression of functional domains and immunoepitopes.
AB  - Vitronectin (Vn) circulates in plasma primarily in the native, monomeric form,
      whereas platelet-associated Vn in conformationally altered and multimeric. Here,
      we report that denatured Vn specifically binds to L-Arg, whereas the L-Arg
      binding site is cryptic in the native form of Vn. In addition, combined treatment
      of disulfide-linked Vn multimers with L-Arg, urea, and reducing agent results in
      the formation of disperse oligomers with reduced expression of denaturation
      sensitive epitopes. These results suggest that L-Arg modulates the partitioning
      between monomeric and multimeric Vn species and that L-Arg affinity
      chromatography can be employed to test for exposure of conformationally sensitive
      binding sites in Vn. The effects of denaturation on the exposure of
      conformationally sensitive epitopes in the N-terminus of Vn is controversial.
      Treatment of Vn with reducing agents abolished type 1 plasminogen activator
      inhibitor and antibody binding to the highly disulfide-linked N-terminal
      somatomedin B domain (amino acids 1 to 51), whereas epitopes located in the
      connecting region/first hemopexin-like repeat (amino acids 52 to 239) and the
      glycosaminoglycan binding domain (amino acids 343-379) were not affected. These
      observations indicate that appropriate disulfide-linkage of the N-terminal
      somatomedin B domain is required for ligand binding and that published
      differences on the effects of denaturation on the expression of binding sites are
      probably due to the use of reducing agents in the denaturation process.

PMID- 9242986
TI  - Polyadenylated mRNA in Escherichia coli: modulation of poly(A) RNA levels by
      polynucleotide phosphorylase and ribonuclease II.
AB  - The effect of 3'-exoribonucleases on the polyadenylation of mRNA in Escherichia
      coli was studied by comparing the synthesis and levels of poly(A) RNA in wild
      type E coli and mutant strains defective in the two major 3'-exoribonucleases:
      polynucleotide phosphorylase and ribonuclease II. Mutations which substantially
      reduced the activity of these 3'-exonucleases caused a 10-fold increase in pulse
      labeling of total poly(A) RNA in intact cells. When the net rate of RNA synthesis
      was measured in permeabilized cells, the mutant with defective 3'-exonucleases
      showed 20- to 60-fold increased synthesis of total poly(A) RNA as well as of
      specific polyadenylated mRNAs, with less than two-fold changes in non-poly(A)
      RNA. Measurement of mRNA polyadenylation in permeable cells under conditions when
      3'-exoribonucleases were inactive showed a 6-fold higher rate of poly(A)
      synthesis in the exonuclease-deficient mutant strain, suggesting a higher
      concentration of mRNA 3'-ends amenable to polyadenylation. Steady-state levels of
      poly(A) RNA, measured by the ability to serve as template for oligo(dT)-dependent
      complementary DNA synthesis, also increased more than 40-fold when the 3'
      exonucleases were inactivated. Monitoring of the length of the poly(A) tracts by
      denaturing polyacrylamide gel electrophoresis showed chain lengths of up to 45
      residues in the 3'-exonuclease-deficient mutant, whereas most of the poly(A)
      tracts in the parent strain were shorter than 12 residues. These results show
      that 3'-exonucleases reduce the level of polyadenylated mRNA in E coli not merely
      by causing its degradation but also by reducing its rate of synthesis, presumably
      by competing with poly(A) polymerase for the 3'-ends of mRNA.

PMID- 9242987
TI  - Involvement and identification of a lysine in the PPi-site of pyrophosphate
      dependent phosphofructokinase from Giardia lamblia.
AB  - The substrate binding and/or catalytic site of the pyrophosphate-dependent
      phosphofructokinase (PPi-PFK) of Giardia lamblia was investigated using an ATP
      affinity label, 2',3'-dialdehyde of ATP, oxidized ATP (oATP), for the involvement
      of lysine residues. The enzyme, which uses PPi rather than ATP as a substrate was
      inhibited by low concentrations of oATP. Oxidized ATP behaves as an affinity
      label for the substrate binding site as evidenced by saturation kinetics with the
      formation of reversible complex prior to inactivation, and the observation that
      the inactivation was stoichiometric with the amount of oATP incorporated which
      extrapolated to 1 mol per mol of monomeric PPi-PFK. The critical lysine modified
      by oATP is proposed to be located at the PPi-binding site since complete
      protection is afforded by PPi; and under steady-state, PPi was competitive with
      the inhibitor. Other substrates of the reaction in either the forward or reverse
      direction did not completely protect against inactivation. This is further
      confirmed by the non-competitive inhibition displayed by either Pi or fructose
      1,6, bisphosphate. Furthermore, the Km values for Pi and fructose 1,6
      bisphosphate of the oATP-modified enzyme were not altered. The oATP-modified
      peptides were analyzed by HPLC peptide mapping, and the profile showed a major
      peak absorbing at 258 nm, which was absent when the modification was carried out
      in the presence of MgPPi. This peptide was sequenced and found to contain Lys
      497. These results suggest that the essential lysine-497 modified by oATP is
      involved in the binding and/or catalysis of PPi and that an ATP-type of binding
      domain, with reference to the phosphoryl groups, is present in the PPi-dependent
      phosphofructokinase of Giardia.

PMID- 9242988
TI  - Trehalase of Dictyostelium discoideum: inhibition by amino-containing analogs of
      trehalose and affinity purification.
AB  - The inhibitory effects of three nitrogen containing analogs of trehalose,
      validamycin A, MDL 25,637 and castanospermine, on Dictyostelium discoideum
      trehalase were examined. Prior to this study, the effects of glycohydrolase
      inhibitors on D discoideum trehalase have not been reported. Validamycin A, MDL
      25,637 and castanospermine were found to be potent, reversible, competitive
      inhibitors of D discoideum vegetative trehalase in vitro with IC50 values of 1 x
      10(-9) M, 2 x 10(-8) M and 1.25 x 10(-4) M, respectively. Validamycin A and MDL
      25,637 also exhibited time-dependent inhibition of D discoideum trehalase,
      whereby the potencies of these two inhibitors were observed to increase when pre
      incubated with the enzyme for up to 60 min. The competitive natures of
      validamycin A and MDL 25,637 were also altered during pre-incubation with enzyme
      such that the compounds behaved as mixed inhibitors under these conditions. Taken
      together, these results suggest that the inhibitory action of validamycin A and
      MDL 25,637 on trehalase is of a slow-binding nature. A trehalase-specific
      affinity resin was synthesized by covalently coupling validamycin A to Sepharose
      6B. This resin was used to purify D discoideum trehalase to near homogeneity in a
      two-step procedure. SDS-PAGE of affinity-purified trehalase, and silver staining
      or in situ staining for trehalase activity, revealed a major protein species of
      42 kDa, exhibiting trehalase activity, and two minor protein species of
      approximately 45 and 49 kDa. Since validamycin A demonstrates strict binding
      specificity for trehalase, validamycin A-Sepharose has potential and novel
      applications in rapid, large scale, purification of trehalases from a variety of
      species origins.

PMID- 9242989
TI  - Blood transfusion in sickle cell disease.
AB  - Blood transfusion can be life-saving in sickle cell disease. There is an
      increasing body of literature available to help define its place in this patient
      population. In this review, we have brought together the reported trials, case
      reports and our experience to discuss the role of transfusion now and in the
      future for sickle cell disease. Advances are continually being made in all fields
      and we have in addition. considered the relevant ones from immunohaematology,
      virology and clinical medicine so that their impact on the subject is taken into
      consideration.

PMID- 9242990
TI  - Thrombophilia and fetal loss.
AB  - Recurrent fetal loss and other placental vascular pathologies of pregnancy have
      long been associated with antiphospholipid syndrome-an acquired autoimmune
      thrombophilic state. The number of known heritable thrombophilic disorders has
      grown rapidly in recent years with the identification of activated protein C
      resistance, factor V Leiden mutation and hyperhomocysteinemia as major causes of
      thrombosis. Data accumulated over the past two years suggest that heritable
      thrombophilia is associated with increased risk of fetal loss and pre-eclampsia.
      The present review discusses potential pathogenetic mechanisms for this
      association and evaluates reported therapeutic regimes for the prevention of
      fetal loss in women with thrombophilia.

PMID- 9242991
TI  - Purging autologous bone marrow with monoclonal antibodies for transplantation in
      acute myelogenous leukemia.
AB  - Myeloablative chemotherapy followed by allogeneic bone marrow rescue is
      considered curative therapy and offers an alternative approach to consolidate
      patients with acute myelogenous leukemia who achieve a first complete remission
      after standard induction chemotherapy. In patients transplanted during second or
      third complete remission, allogeneic transplantation can also be curative,
      although there is lower relapse-free survival. Despite the success of this
      treatment modality, only 10-20% of patients will be eligible to receive an
      allogeneic transplantation due to advanced age or lack of an HLA-matched donor.
      In this situation, autologous bone marrow transplantation allows therapy of
      comparable intensity to be administered with less morbidity and mortality due to
      the lack of graft-versus-host disease. In contrast to allografts, remission
      autografts may harbor residual occult malignant cells unable to be grossly
      detected. The infusion of these malignant cells following myeloablative therapy
      can contribute to leukemia relapse. Various in vitro approaches to 'purge' occult
      malignant leukemia cells from remission marrows have been developed. The two
      techniques that have been studied in preclinical and clinical trials include
      pharmacological and monoclonal antibody-mediated methods. The efficacy of using
      the latter to purge autografts compared with the use of unpurged autografts in
      patients with acute myelogenous leukemia undergoing autologous bone marrow
      transplantation is currently the focus of a prospective multicenter trial.

PMID- 9242992
TI  - Human T-cell leukemia viruses: epidemiology, biology, and pathogenesis.
AB  - The human T-cell lymphotropic viruses type I and type II are closely related
      human retroviruses that have similar biological properties, genetic organization
      and tropism for T lymphocytes. Along with the simian T-cell lymphoma virus type
      I, they define the group of retroviruses known as the primate T-cell
      leukemia/lymphoma viruses. Initially identified in 1980, the human T-cell
      lymphotropic virus type I has been implicated as the etiologic agent of adult T
      cell leukemia/lymphoma and of a degenerative neurologic disorder known as
      tropical spastic paraparesis or human T-cell lymphotropic virus type I-associated
      myelopathy. The intriguing link between human T-cell lymphotropic virus type, T
      cell malignancy, and a totally unrelated and non-overlapping neurological
      disorder suggests divergent and unique pathogenetic mechanisms. This review will
      address the epidemiology, molecular biology, and pathogenesis of human T-cell
      leukemia viruses.

PMID- 9242993
TI  - Molecular histocompatibility typing in unrelated donor bone marrow
      transplantation.
AB  - Increasing numbers of bone-marrow transplants are being performed with marrow
      from unrelated donors. There is clear evidence that genetic disparity is a major
      cause of graft-versus-host disease. However, until very recently, typing methods
      did not have sufficient resolution to identify the majority of histocompatibility
      alleles. DNA-based typing methods have the potential to define alleles
      unequivocally, and this will help in the selection of better matched marrow
      donors. Also, a number of studies have indicated that patient and donor pairs
      that had previously been identified as matched can frequently be shown to have
      been mismatched at one or more locus. Consequently, it may become more difficult
      in future to find completely matched donors. There is also evidence that some
      genetic mismatching may not be deleterious to the patient and it may now be
      possible to analyse the histocompatibility data with greater confidence and
      identify those mismatches that are tolerated. This will allow a larger number of
      transplants to be performed using unrelated donors.

PMID- 9242995
TI  - Development of PCR-based techniques to identify porcine transmissible
      gastroenteritis coronavirus isolates.
AB  - Sixteen isolates of transmissible gastroenteritis virus and one isolate of
      porcine respiratory coronavirus were characterized using RT-PCR amplification of
      4 antigenic subsites in the site A epitope on the TGEV spike gene. The PCR
      products were digested with restriction enzymes Sau3AI and SspI and the sizes of
      the fragments were determined. Three different digestion patterns were observed
      with each enzyme. The recognition site for Sau3AI was missing in 1 isolate, was
      present in 13 isolates and 3 isolates had 2 sites. PCR-products with a single
      site had 3 different fragment sizes and the other isolates produced 2 fragments
      with different sizes. The SspI recognition site was not present in 5 isolates and
      12 isolates had a single site that produced 2 fragments of different sizes. Based
      on the restriction fragment sizes, the 17 isolates were separated into 7 groups.
      Direct sequencing of the 455 bp nested set fragments demonstrated greater than
      96% sequence homology among the 16 isolates and 100% homology in the 4 antigenic
      subsites in the conserved site A epitope. The groups are discussed in relation to
      their sequence homology and virulence. In vitro procedures have been developed to
      identify several porcine enteric coronavirus isolates at the strain level.

PMID- 9242994
TI  - Comparative study of serological methods for the detection of antibodies to
      porcine reproductive and respiratory syndrome virus.
AB  - A comparison was made of serological diagnostic methods used for the detection of
      antibodies against porcine reproductive and respiratory syndrome (PRRS) virus. In
      the "phase I" PRRS test panel comparison, a panel of sera collected from 135 pigs
      of various ages, from North American herds with and without PRRS histories, were
      sent to 4 different laboratories and tested by an indirect immunofluorescent
      assay (IFA), an immunoperoxidase monolayer assay (IPMA) and an indirect enzyme
      linked immunosorbent assay (iELISA). In the "phase II" PRRS test panel
      comparison, a panel of 382 sera collected from pigs of various ages, PRRS
      histories, and from various locations in North America and France, were divided
      into 2 panels (A & B) and sent to 3 Canadian laboratories and tested by the IFA
      and iELISA. In the phase I comparison, agreement between the IFA of laboratory 4
      and the iELISA and IPMA of laboratory 3 was excellent (kappa values of 95% and
      98%, respectively). This contrasted with the poor agreement between these
      laboratories and the IFA results of laboratories 1 and 2 in the phase I trial. In
      the phase II comparison, the results demonstrated good agreement between various
      tests both within and between laboratories. The overall performance of the iELISA
      was superior in the combination of sensitivity (96.1%) and specificity (100%)
      relative to the reference classification of the serum samples and repeatability
      (kappa value 98%). The iELISA is technically superior to IFA and IPMA, time
      efficient, cost effective and suitable for testing of a large number of samples
      over a short period of time. Thus, the iELISA may be a better alternative to IFA
      or IPMA for routine detection of PRRS viral antibodies in swine sera.

PMID- 9242996
TI  - Utilization of both phenotypic and molecular analyses to investigate an outbreak
      of multidrug-resistant Salmonella anatum in horses.
AB  - Phenotypic and molecular techniques, including antimicrobial susceptibility
      testing, plasmid analysis, and pulsed-field gel electrophoresis (PFGE) were used
      to characterize 15 isolates of multidrug-resistant (MDR) Salmonella anatum
      cultured during a 16 mo period from horses and a veterinary clinic environment.
      The isolates were resistant to multiple antimicrobial agents and could be placed
      into 4 groups based on their antimicrobial resistance patterns. The isolates
      contained multiple plasmids ranging in size from 2 to > 100 kb that could be
      grouped into 3 different plasmid profile patterns; these patterns did not
      correlate with the antimicrobial resistance groupings. Furthermore, antimicrobial
      resistance was conjugatively transferable. Digestion of genomic DNA from the 15
      isolates with 3 different restriction endonucleases, SfiI, SpeI, and XbaI
      followed by PFGE revealed a highly conserved restriction endonuclease digestion
      pattern. In contrast, diverse banding patterns were observed with S. anatum
      obtained from other sources. These observations suggest that the MDR S. anatum
      isolates represent a common outbreak strain even though they possess different,
      albeit similar, antibiograms and plasmid profiles. The study showed that PFGE is
      a useful epidemiological tool for discriminating between unrelated and outbreak
      related strains of S. anatum. In conclusion, epidemiological studies of outbreaks
      caused by MDR isolates of S. anatum should consist of both genotypic and
      phenotypic methods of analysis.

PMID- 9242997
TI  - Decreased serum apolipoprotein A-I concentrations in cows infected with
      Salmonella typhimurium.
AB  - Serum apolipoprotein A-I concentrations in cows infected with Salmonella
      Typhimurium were evaluated to assess its relevance in salmonellosis.
      Apolipoprotein A-I has been shown in rats to be secreted by the intestine as well
      as the liver. Clinical symptoms such as diarrhea revealed an outbreak of
      salmonellosis in 22 cows on a farm, and sera were obtained at 6 (acute phase),
      16, 28 (convalescent period) and 42 d (postconvalescent period) after the
      outbreak. Apolipoprotein A-I concentrations (mean +/- SD, mg/mL), determined by
      ELISA, were 0.598 +/- 0.497 (day 6), 0.111 +/- 0.060 (day 16), 0.432 +/- 0.311
      (day 28) and 0.727 +/- 0.516 (day 42). Compared with the concentration at day 42,
      those at 16 and 28 d were significantly (P < 0.01, P < 0.05) lower, but that at
      day 6 was not. The serum concentration of apolipoprotein B-100 (of liver origin
      in cattle) was unaltered during the course of salmonellosis. The concentration of
      apolipoprotein A-I was positively correlated with those of serum total
      cholesterol (r = 0.589, P < 0.01) and phospholipids (r = 0.590, P < 0.01). These
      results suggest that apolipoprotein A-I in cattle is in part of intestinal
      origin, and also that its decreased serum concentration in salmonellosis can be
      attributed to the reduced intestinal synthesis or secretion of this
      apolipoprotein. Moreover, as a potential carrier for dietary lipids such as
      cholesterol, determination of serum apolipoprotein A-I concentration is suggested
      to be useful when assessing the nutritional status of the affected cows.

PMID- 9242998
TI  - Treatment of experimentally induced pneumonic pasteurellosis of young calves with
      tilmicosin.
AB  - Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally
      infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella
      haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals
      received either: 1) Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a
      single injection of 10 mg tilmicosin per kg body weight (n = 12). Calves that
      were non-infected and tilmicosin-treated were also included for determining
      tilmicosin concentrations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and
      72 h (n = 3-per time). In the infected calves, response to therapy was monitored
      clinically. Serum samples were collected for determination of tilmicosin
      concentrations using HPLC. Any animal becoming seriously ill was humanely killed.
      Complete necropsy examinations were performed on all animals and included gross
      pathologic changes, bacteriologic analysis, histopathology, and determination of
      pulmonary concentrations of tilmicosin. Tilmicosin treated animals responded
      significantly better to therapy than saline-treated control calves. Clinical
      assessment of calves during the study indicated that tilmicosin-treated calves
      had significantly improved by T = 8 h compared to satine-treated animals (P <
      0.05). At necropsy tilmicosin-treated calves had significantly less severe gross
      and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline
      treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while
      of the tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica.
      Mean (+/- standard error) serum tilmicosin concentrations in infected calves
      peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased
      to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P.
      haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to
      serum concentrations of tilmicosin in non-infected tilmicosin-treated calves.
      Lung tissue concentrations of the antibiotic were comparatively high, even at 72
      h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were
      significantly higher in experimentally infected calves than in non-infected
      tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was
      effective in treating experimentally-induced pneumonic pasteurellosis as
      determined by alleviation of clinical signs, pathological findings at post
      mortem, and presence of viable bacteria from the lung. Concentrations
      substantially above MIC for P. haemolytica were present in lung tissue even at 72
      h following a single subcutaneous injection of 10 mg tilmicosin per kg body
      weight.

PMID- 9242999
TI  - Presence of pap-, sfa-, and afa-related sequences in necrotoxigenic Escherichia
      coli isolates from cattle: evidence for new variants of the AFA family.
AB  - Necrotoxigenic Escherichia coli (NTEC) are associated with intestinal and
      extraintestinal diseases in animals and human beings and produce Cytotoxic
      Necrotizing Factor 1 (CNF1) or 2 (CNF2). Fourty-three NTEC1, 42 NTEC2, and 32 CNF
      negative isolates from cattle were tested by colony DNA hybridization, by plasmid
      DNA hybridization and by PCR assays for the presence of DNA sequences homologous
      to the operons coding for fimbrial (PAP/PRS, SFA/FIC, and F17) and afimbrial
      (AFA/Dr) adhesins of extraintestinal E. coli. Most NTEC1 isolates hybridized with
      the PAP probes and either the SFA probe (37%) or the AFA probes (49%). Most NTEC2
      isolates, in contrast, hybridized with the F17 probe (45%), the AFA probes (19%),
      or the F17 and AFA probes (22%). A probe-positive plasmid was identified in each
      of the 19 NTEC2 isolates studied. They all hybridized with the CNF2 toxin probe
      (Vir plasmids) and most of them with the F17 (6 plasmids) or AFA (7 plasmids)
      probes. PCR amplification was obtained with 6 of the 11 NTEC isolates tested for
      the papGII/prsG genes; with all 5 NTEC isolates tested for the sfa and related
      operons; but with none of the 18 NTEC isolates tested for the afa and related
      operons. pap-, sfa-, and afa-related sequences are thus present in NTEC isolates
      from cattle in addition to f17-related operons and may code for adhesins
      corresponding to specific colonization factors. f17- and afa-related sequences
      can be located on the Vir plasmids along with the cnf2 gene. Existence of new
      variants of the AFA/Dr family is evident from the negative results of this family
      specific PCR assay.

PMID- 9243000
TI  - Interaction of Haemophilus parasuis with nasal and tracheal mucosa following
      intranasal inoculation of cesarean derived colostrum deprived (CDCD) swine.
AB  - Twenty-three cesarean derived, colostrum deprived pigs were obtained at 5 wk of
      age and inoculated intranasally with either 1.4 x 10(8) colony forming units of
      Haemophilus parasuis or sterile phosphate buffered saline. Pigs were euthanized
      at 4, 8, 12, 18, 26, or 36 h post-inoculation and tissues from the oropharynx and
      respiratory tract were obtained for qualitative bacterial culture,
      immunohistochemistry for H. parasuis antigens, and light and transmission
      electron microscopy. Haemophilus parasuis was consistently isolated from the
      nasal cavity (17/17, 100%) and trachea (13/17, 76%) and rarely isolated from the
      lung (3/17, 18%) and blood stream (1/17, 6%) of infected pigs. Antigens of H.
      parasuis were sporadically detected on the nasal mucosa (6/17, 35%) and trachea
      (8/17, 47%). Light microscopic lesions included submucosal and intraepithelial
      infiltrates of neutrophils and infrequent, patchy loss of cilia. Ultrastructural
      changes in nasal mucosal epithelial cells included cell protrusion, loss of
      cilia, and dilation of the cytocavitary network. Bacteria were infrequently
      identified and were either within an amorphous material at the apical surface of
      the cilia or were between individual cilia. These results suggest H. parasuis
      associates with the nasal mucosa and can induce a suppurative rhinitis with nasal
      mucosal epithelial cell degeneration. This process may represent an initial event
      in the pathogenesis of H. parasuis infection of swine.

PMID- 9243001
TI  - Bovine IgG2a antibodies to Haemophilus somnus and allotype expression.
AB  - Bovine IgG2a has been implicated in protection against pyogenic infections,
      including those caused by Haemophilus somnus. To further investigate the role of
      IgG2a in defense against H. somnus, IgG1 and IgG2a antibodies were purified from
      antiserum against an immunodominant 40 kDa outer membrane protein (p40) of H.
      somnus, which was previously shown to passively protect calves against H. somnus
      pneumonia. The passive protective capacity of anti-p40 IgG1 or IgG2a was
      evaluated in vivo in calves. Purified anti-p40 IgG1 or IgG2a was incubated with
      H. somnus for 15 min before intrabronchial inoculation of calves. Bacteria
      incubated with anti-p40 IgG1 or IgG2a were inoculated into one caudal lung lobe
      and bacteria incubated with IgG1 or IgG2a from the respective preimmunization
      serum were inoculated into the contralateral lobe. The volumes of pneumonia in
      the right and left lungs were determined 24 h later. The difference in volume of
      pneumonia with H. somnus preincubated in IgG1 pre- and postimmunization anti p40
      was less (16 cm3, P = 0.298) than the difference in volume of pneumonia with H.
      somnus preincubated in IgG2a pre- and postimmunization anti p40 (30 cm3, P =
      0.146). Although the differences in lesion size between pre- and postimmunization
      serum were not statistically significant, the trend suggests IgG2a may be more
      protective than IgG1. To examine this further, the peptide specificity of these
      IgG1 and IgG2a antibodies to p40 was examined. After limited proteolysis of p40,
      IgG2a antibodies reacted with 2 peptides not recognized by IgG1 antibodies. Other
      peptides were recognized by both isotypes. Since these studies suggested that
      IgG2a may be important in protection against infection, we then investigated some
      aspects of the role of the 2 IgG2a allotypes, A1 and A2. In retrospective studies
      of age differences in expression of IgG2a allotypes, no heterozygotes were
      detected in calves of 60 d old or less, and fewer heterozygotes were detected in
      calves 61-120 d old than in cattle older than 270 d (P < 0.01). In a subsequent
      prospective study of the time course of allotype expression, Holstein calves
      shown to be heterozygotes expressed the IgG2aA1 allotype early but the IgG2aA2
      allotype was not usually detected until 3 to 4 mo of age. Thus, both the
      retrospective and the prospective studies showed age related differences in
      expression of the IgG2aA1 and A2 allotypes. This could have implication in
      protection.

PMID- 9243002
TI  - Modulation of the effects of norepinephrine uptake inhibitors on the
      norepinephrine-induced contractile response of the porcine uterine artery during
      early pregnancy.
AB  - The effects of norepinephrine (NE) uptake inhibitors on the porcine uterine
      artery's contractile response to NE and their potential alteration during early
      pregnancy (Day 13 postcoitus; day of coitus = Day 0) in comparison with the end
      of the luteal phase (Days 11-14; first day of behavioral estrus = Day 0) was
      investigated. This pregnancy time point is characterized by a transient increase
      in resting uterine blood flow dependent on the presence of blastocysts, an
      increased endometrial vascular permeability, and the beginning of the endometrial
      attachment of the blastocysts. A cumulative concentration-response curve (CCRC)
      to NE was produced in isometrically-mounted rings. Cocaine (5 microM) was used to
      inhibit neuronal NE uptake and hydrocortisone (30 microM) was used to inhibit
      extraneuronal NE uptake. Either drug alone induced a leftward shift of the CCRC
      to NE without affecting the maximal response. This shift had the same amplitude
      at the end of the luteal phase and in early pregnancy. However, the leftward
      shift induced by cocaine was larger than that induced by hydrocortisone only in
      early pregnancy, and the leftward shift induced by exposure to both
      hydrocortisone and cocaine was larger in early pregnancy than at the end of the
      luteal phase. These results suggest that a significant sensitization of the
      contractile response of the porcine uterine artery to NE is induced by neuronal
      and extraneuronal uptake inhibitors and that this effect is altered in early
      pregnancy, possibly reflecting the existence of a mechanism protecting the
      uterine artery against excessive sympathetic stimulation.

PMID- 9243003
TI  - The arrhythmogenic dose of epinephrine in halothane and isoflurane anesthetized
      dogs: an assessment of repeatability.
AB  - Repeat determinations of the arrhythmogenic dose of epinephrine (ADE) were made
      over two 6 h periods on 2 separate days during halothane and isoflurane
      anesthesia. Each of 6 dogs underwent 4 trials (2 halothane and 2 isoflurane).
      During each trial, the ADE was determined at baseline, 3 and 6 h. Epinephrine was
      infused for 3.0 min at increasing dose rates (2.5, 5.0, 10.0 and 20.0 mg/kg/min)
      until the arrhythmia criterion (4 or more intermittent or continuous premature
      ventricular contractions) was reached. The inter-infusion interval was 20 min.
      There were no significant differences in the measured cardiovascular parameters
      (SBP, DBP, MBP, and HR), arterial blood gases, or acid-base status prior to each
      determination during a single trial. The cardiovascular responses to epinephrine
      infusion were not significantly different between inhalants or determinations.
      The range of the ADE determined over both trials during isoflurane anesthesia was
      30.12 +/- 12.21 micrograms/kg to 50.83 +/- 9.17 micrograms/kg. The baseline ADE
      during Day 1 of halothane anesthesia (6.70 +/- 1.36 micrograms/kg) was
      significantly greater than ADE determinations at 3 (4.65 +/- 0.88 micrograms/kg)
      and 6 h (4.61 +/- 0.87 micrograms/kg). The reduction in the ADE over time during
      day 2 of halothane anesthesia was not statistically significant (P = 0.0669).
      These results suggest that during halothane anesthesia, the ADE is not repeatable
      over time, and they may influence our interpretation of the results of
      investigations that measure alterations in the ADE due to pharmacological
      manipulations without repeated control ADE determinations.

PMID- 9243004
TI  - Magnesium status and the effect of magnesium supplementation in feline
      hypertrophic cardiomyopathy.
AB  - Magnesium deficiency has been associated with the development of cardiovascular
      disease in several species. Cats may be predisposed to alterations in magnesium
      status because of recent changes in the composition of commercial feline diets.
      The purposes of this study were 1) to examine the dietary history of cats with
      hypertrophic cardiomyopathy (HCM), 2) to study magnesium status of cats with HCM
      compared to normal cats, and 3) to determine the effects of magnesium
      supplementation in cats with HCM. In part 1 of the study, diets of 65 cats with
      HCM were examined retrospectively. Forty of the 45 cats for which diets could be
      determined (89%) ate a diet designed to be magnesium-restricted and/or to produce
      an acidic urine. In part 2 of the study, 10 cats with HCM were compared to 10
      healthy control cats for serum creatinine and magnesium; urine creatinine and
      magnesium, urine specific gravity and pH, and fractional excretion of magnesium.
      Urine creatinine and specific gravity were higher in control cats than in cats
      with HCM. No other differences were found between the 2 groups. In part 3, cats
      with HCM were supplemented with either 210 mg magnesium chloride (n = 15) or 210
      mg lactose (n = 15) for 12 wk. No differences between the 2 groups were found for
      changes in either magnesium status or echocardiographic parameters. However, the
      30 cats with HCM, as a group, did show significant improvements in measures of
      cardiac hypertrophy over the 12-week period. This was likely the result of
      treatment with other medications, rather than the magnesium supplementation. The
      results of this study suggest that cats with HCM are likely to be fed magnesium
      restricted diets, but that they do not appear to have altered magnesium status
      compared to healthy controls.

PMID- 9243005
TI  - Crystal violet staining of Bordetella bronchiseptica colonies for differentiation
      of phase-I strains from variant strains in degraded phases.
AB  - After 2 days of growth on Brain heart infusion agar (BHIA) at 38 degrees C, phase
      I colonies and degraded-phase colonies of Bordetella bronchiseptica could be
      differentiated by their ability to take up crystal violet (CV). Phase-I colonies
      in X mode, but not colonies in degraded phases (phases II, III, and rough) bound
      CV. Phenotypically-altered C-mode colonies (grown at 32 degrees C or lower
      temperatures) also lacked this ability. CV staining offers an easy method for the
      recognition of different colony types that appear identical when observed on
      BHIA.

PMID- 9243006
TI  - Biochemistry reference values for Quebec lactating dairy cows, nursing sows,
      growing pigs and calves.
AB  - Reference values for lactating dairy cows, nursing sows, growing calves and pigs
      were established on jugular cannulated animals. On each day of sampling, 13
      samples were taken every hour from dairy cattle, growing calves and pigs and 5
      samples were taken every 2 h from nursing sows to minimize day and analysis bias.
      Results show that aging influences more biochemical factors in pigs than in
      calves, and in nursing sows variations observed between day 5 and 15 after
      farrowing are of greater amplitude than between day 15 and 25.

PMID- 9243007
TI  - Hyperthermophiles in the history of life.
AB  - Prokaryotes requiring extremely high growth temperatures (optimum 80-110 degrees
      C) have recently been isolated from water-containing terrestrial, subterranean
      and submarine high temperature environments. These hyperthermophiles consist of
      primary producers and consumers of organic matter, forming unique high
      temperature ecosystems. Surprisingly, within the 16S rRNA-based phylogenetic
      tree, hyperthermophiles occupy all the shortest and deepest branches closest to
      the root. Therefore, they appear to be the most primitive extant organisms. Most
      of them (the primary producers) are able to grow chemolithoautotrophically, using
      CO2 as sole carbon source and inorganic energy sources, suggesting a
      hyperthermophilic autotrophic common ancestor. They gain energy from various
      kinds of respiration. Molecular hydrogen and reduced sulfur compounds serve as
      electron donors while CO2, oxidized sulfur compounds, NO3- and O2 (only rarely)
      serve as electron acceptors. Growth demands of hyperthermophiles fit the scenario
      of a hot volcanism-dominated primitive Earth. Similar anaerobic
      chemolithoautotrophic hyperthermophiles, completely independent of a sun, could
      even exist on other planets provided that active volcanism and liquid water were
      present.

PMID- 9243009
TI  - Hydrothermal systems as environments for the emergence of life.
AB  - Analysis of the chemical disequilibrium provided by the mixing of hydrothermal
      fluids and seawater in present-day systems indicates that organic synthesis from
      CO2 or carbonic acid is thermodynamically favoured in the conditions in which
      hyperthermophilic microorganisms are known to live. These organisms lower the
      Gibbs free energy of the chemical mixture by synthesizing many of the components
      of their cells. Primary productivity is enormous in hydrothermal systems because
      it depends only on catalysis of thermodynamically favourable, exergonic
      reactions. It follows that hydrothermal systems may be the most favourable
      environments for life on Earth. This fact makes hydrothermal systems logical
      candidates for the location of the emergence of life, a speculation that is
      supported by genetic evidence that modern hyperthermophilic organisms are closer
      to a common ancestor than any other forms of life. The presence of hydrothermal
      systems on the early Earth would correspond to the presence of liquid water.
      Evidence that hydrothermal systems existed early in the history of Mars raises
      the possibility that life may have emerged on Mars as well. Redox reactions
      between water and rock establish the potential for organic synthesis in and
      around hydrothermal systems. Therefore, the single most important parameter for
      modelling the geochemical emergence of life on the early Earth or Mars is the
      composition of the rock which hosts the hydrothermal system.

PMID- 9243008
TI  - Phylogenetic perspective on microbial life in hydrothermal ecosystems, past and
      present.
AB  - Understanding hydrothermal ecosystems, both past and present, requires basic
      information on the types of organisms present. Traditional methods, which require
      cultivation of microorganisms, fail to detect many taxa. We have used
      phylogenetic analyses of small subunit rRNA sequences obtained from
      microorganisms of a hot spring in Yellowstone National Park to explore the
      archael (archaebacterial) diversity present. Analysis of these sequences reveals
      several novel groups of archaea, greatly expanding our conception of the
      diversity of high temperature microorganisms, and demonstrating that hydrothermal
      systems harbour a rich variety of life. Many of these groups diverged from the
      archael line of descent early during evolution, and an understanding of their
      common properties may assist in inference of the nature of the last common
      ancestor of all life. The data also show a specific relationship between low
      temperature marine archaea and some hot spring archaea, consistent with a
      thermophilic origin of life. Future use of rRNA-sequence-based techniques in
      exploration of hydrothermal systems should greatly facilitate study of modern
      thermophiles and give us insight into the activities of extinct communities as
      well.

PMID- 9243010
TI  - Chemical and physical context for life in terrestrial hydrothermal systems:
      chemical reactors for the early development of life and hydrothermal ecosystems.
AB  - The diversity of terrestrial hot spring systems, resulting from the large scale
      coupled transfer of heat and mass in the Earth's crust, maximizes opportunities
      for evolving ecosystems by the continuous supply of nutrients (P, N, C, S)
      together with the metals (e.g. K, Mg, Mo, Zn) essential to biogenesis. Cyclic,
      evaporative micro-environments are common, and potentially catalytic mineral
      surfaces are also continually created through rock alteration and mineral
      deposition in and around hot springs. These dynamical systems constitute highly
      interactive, open, chemical environments capable of establishing complex
      biochemical microreactors. Volcanic collapse settings on oceanic islands, provide
      a highly dynamic scenario for the initiation of life and development of diverse
      ecosystems at the earliest stages of development of the Earth's crust.

PMID- 9243011
TI  - Stable light isotope biogeochemistry of hydrothermal systems.
AB  - The stable isotopic composition of the elements O, H, S and C in minerals and
      other chemical species can indicate the existence, extent, conditions and the
      processes (including biological activity) of hydrothermal systems. Hydrothermal
      alteration of the 18O/16O and D/H values of minerals can be used to detect fossil
      systems and delineate their areal extent. Water-rock interactions create isotopic
      signatures which indicate fluid composition, temperature, water-rock ratios, etc.
      The 18O/16O values of silica and carbonate deposits tend to increase with
      declining temperature and thus help to map thermal gradients. Measurements of D/H
      values can help to decipher the origin(s) of hydrothermal fluids. The 34S/32S and
      13C/12C values of fluids and minerals reflect the origin of the S and C as well
      as oxygen fugacities and key redox processes. For example, a wide range of
      34S/32S values which are consistent with equilibration below 100 degrees C
      between sulfide and sulfate can be attributed to sulfur metabolizing bacteria.
      Depending on its magnitude, the difference in the 13C/12C value of CO2 and
      carbonates versus organic carbon might be attributed either to equilibrium at
      hydrothermal temperatures or, if the difference exceeds 1% (10/1000), to organic
      biosynthesis. Along the thermal gradients of thermal spring outflows, the 13C/12C
      value of carbonates and 13C-depleted microbial organic carbon increases,
      principally due to the outgassing of relatively 13C-depleted CO2.

PMID- 9243012
TI  - High temperature ecosystems and their chemical interactions with their
      environment.
AB  - Phototrophic thermal ecosystems consist of microbial mats whose composition is
      largely determined by water temperature, dissolved oxygen, sulfide and pH. Mats
      exposed to sunlight consist of an upper zone of phototrophic bacteria and
      cyanobacteria and an undermat of heterotrophic bacteria. There is little or no
      net accumulation of reduced carbon and a quasi-equilibrium is established between
      the synthesis and oxidation of reduced carbon. The flux of carbon and other
      metabolites induces chemical change in the interstitial water which may assist
      the deposition of hydrothermal minerals. Uptake of carbon dioxide by phototrophs
      is favourable to calcium carbonate (travertine) deposition. Thermal systems also
      contain a range of chemolithotrophs and sulfate reducers potentially capable of
      depositing carbonate. Acid production by sulfate reducers may have the ability to
      precipitate silica from alkaline thermal waters but has not yet been demonstrated
      in vivo. Deposition of thermal ochre is also possible via bacterial oxidation of
      reduced iron and manganese. It appears that bacteria play a minor role in the
      deposition of hydrothermal minerals through chemical interaction. However, they
      may play a more important physical role by providing a large surface are suitable
      for mineral nucleation. If hydrothermal deposits occur on Mars, the distribution
      of travertine is likely to be restricted if there is a lack of pre-existing
      sedimentary carbonate. Less biologically interactive deposits of silica and ochre
      may predominate.

PMID- 9243013
TI  - Ancient hydrothermal ecosystems on earth: a new palaeobiological frontier.
AB  - Thermal springs are common in the oceans and on land. Early in the history of the
      Earth they would have been even more abundant, because of a higher heat flow. A
      thermophilic lifestyle has been proposed for the common ancestor of extant life,
      and hydrothermal ecosystems can be expected to have existed on Earth since life
      arose. Though there has been a great deal of recent research on this topic by
      biologists, palaeobiologists have done little to explore ancient high temperature
      environments. Exploration geologists and miners have long known the importance of
      hydrothermal systems, as they are sources for much of our gold, silver, copper,
      lead and zinc. Such systems are particularly abundant in Archaean and Proterozoic
      successions. Despite the rarity of systematic searches of these by
      palaeobiologists, already 12 fossiliferous Phanerozoic deposits are known. Five
      are 'black smoker' type submarine deposits that formed in the deep ocean and
      preserve a vent fauna like that in the modern oceans; the oldest is Devonian.
      Three are from shallow marine deposits of Carboniferous age. As well as 'worm
      tubes', several of these contain morphological or isotopic evidence of microbial
      life. The oldest well established fossiliferous submarine thermal spring deposit
      is Cambro-Ordovician; microorganisms of at least three or four types are
      preserved in this. One example each of Carboniferous and Jurassic sub-lacustrine
      fossiliferous thermal springs are known. There are two convincing examples of
      fossiliferous subaerial hydrothermal deposits. Both are Devonian. Several known
      Proterozoic and Archaean deposits are likely to preserve a substantial
      palaeobiological record, and all the indications are that there must be numerous
      deposits suitable for study. Already it is demonstrable that in ancient thermal
      spring deposits there is a record of microbial communities preserved as
      stromatolites, microfossils, isotope distribution patterns and hydrocarbon
      biomarkers.

PMID- 9243014
TI  - The Rhynie cherts: an early Devonian ecosystem preserved by hydrothermal
      activity.
AB  - The Rhynie cherts contain a remarkable early Devonian terrestrial to freshwater
      biota preserved in siliceous sinter by the action of a precious-metal-bearing hot
      spring system. Arthropods, vascular and non-vascular plants, algae, fungi and
      cyanobacteria are present. Preservation ranges from perfect 3D cellular
      permineralization to compacted coalified films, and can be related to both
      silicification processes and stages of biological and physical degradation of the
      plants at the time of silicification. Plants occasionally have original subaerial
      vertical axes preserved in growth position, and rhizomes bearing rhizoids. The
      plant litter of the substrate is also partly silicified. Silicification of
      organic material took place in hot spring pools, by surface flooding of areas
      with growing plants, and by permeation of the substrate. Sinters recognized
      include botryoidal geyserite typical of vent margins, and laminated sinter
      comparable with that of modern sinter terraces. Massive, vuggy, brecciated and
      nodular sinter textures are also present. At the microscopic level, textures
      associated with filamentous elements of the biota, and with the preservation of
      plants, closely match those present in modern sinters. Oxygen isotope and organic
      geochemical data from the Rhynie cherts indicate a temperature of 90-120 degrees
      C. This is apparently greater than the temperature at which elements of the biota
      were preserved and represents subsequent shallow burial in the hot spring system.
      The range of temperature and chemistry present at the surface provided high local
      environmental gradients. Current work attempts to identify thermophilic elements
      of the biota and document environmental zonation of biota relative to hot spring
      vents.

PMID- 9243015
TI  - Fossilization processes in siliceous thermal springs: trends in preservation
      along thermal gradients.
AB  - To enhance our ability to extract palaeobiological and palaeoenvironmental
      information from ancient thermal spring deposits, we have studied the processes
      responsible for the development and preservation of stromatolites in modern
      subaerial thermal spring systems in Yellowstone National Park (USA). We
      investigated specimens collected from silica-depositing thermal springs along the
      thermal gradient using petrographic techniques and scanning electron microscopy.
      Although it is known that thermophilic cyanobacteria control the morphogenesis of
      thermal spring stromatolites below 73 degrees C, we have found that biofilms
      which contain filamentous thermophiles contribute to the microstructural
      development of subaerial geyserites that occur along the inner rims of thermal
      spring pools and geyser effluents. Biofilms intermittently colonize the surfaces
      of subaerial geyserites and provide a favoured substrate for opaline silica
      precipitation. We have also found that the preservation of biotically produced
      microfabrics of thermal spring sinters reflects dynamic balances between rates of
      population growth, decomposition of organic matter, silica deposition and early
      diagenesis. Major trends in preservation of thermophilic organisms along the
      thermal gradient are defined by differences in the mode of fossilization,
      including replacement, encrustation and permineralization.

PMID- 9243016
TI  - Lipid biomarkers for bacterial ecosystems: studies of cultured organisms,
      hydrothermal environments and ancient sediments.
AB  - This paper forms part of our long-term goal of using molecular structure and
      carbon isotopic signals preserved as hydrocarbons in ancient sediments to improve
      understanding of the early evolution of Earth's surface environment. We are
      particularly concerned with biomarkers which are informative about aerobiosis.
      Here, we combine bacterial biochemistry with the organic geochemistry of
      contemporary and ancient hydrothermal ecosystems to construct models for the
      nature, behaviour and preservation potential of primitive microbial communities.
      We use a combined molecular and isotopic approach to characterize lipids produced
      by cultured bacteria and test a variety of culture conditions which affect their
      biosynthesis. This information is then compared with lipid mixtures isolated from
      contemporary hot springs and evaluated for the kinds of chemical change that
      would accompany burial and incorporation into the sedimentary record. In this
      study we have shown that growth temperature does not appear to alter isotopic
      fractionation within the lipid classes produced by a methanotropic bacterium. We
      also found that cultured cyanobacteria biosynthesize diagnostic methylalkanes and
      dimethylalkanes with the latter only made when growing under low pCO2. In an
      examination of a microbial mat sample from Octopus Spring, Yellowstone National
      Park (USA), we could readily identify chemical structures with 13C contents which
      were diagnostic for the phototrophic organisms such as cyanobacteria and
      Chloroflexus. We could not, however, find molecular evidence for operation of a
      methane cycle in the particular mat samples we studied.

PMID- 9243017
TI  - The limits of palaeontological knowledge: finding the gold among the dross.
AB  - Palaeontological interpretation rests on two interwoven sets of comparisons with
      the modern world. Palaeobiological interpretation relies on the placement of
      fossils within a phylogenetic and functional framework based primarily on the
      comparative biology of living organisms. Analogy to currently observable
      chemical, physical and taphonomic processes enables palaeoenvironmental
      inferences to be drawn from geological data. In older rocks, comparisons with the
      modern Earth can become tenuous, limiting palaeontological interpretation. The
      problem reaches its apogee in Archaean successions, yet pursuit of multiple lines
      of evidence establishes that complex microbial communities, fuelled by autotrophy
      and, likely, photoautotrophy, existed 3500 million years ago. Although Archaean
      palaeontology has to date focused on silicified coastal sediments, improved
      understanding of Earth's earliest biosphere may depend on the development of
      alternative environmental and taphonomic analogies. Spring precipitates and
      hydrothermal metal deposits are promising candidates. Terrestrial organisms may
      be of limited value in interpreting such fossils as may be found on Mars,
      although some points of comparison could prove general. Given limited
      opportunities for exploration, proper choice of environmental analogy is
      critical. Spring precipitates constitute excellent deposits for addressing
      questions of biology on another planet.

PMID- 9243018
TI  - The role of remote sensing in finding hydrothermal mineral deposits on earth.
AB  - The identification of surface mineralogical composition using hyperspectral
      sensors is now the major remote sensing opportunity for exploration geologists
      seeking refined vectors to potential ore-bearing hydrothermal systems. This
      involves no less than remote, visible and infrared spectroscopy of the molecular
      composition of geological materials from remote platforms using a large number of
      calibrated spectral bands. From field-portable systems to those flying in high
      flying aircraft on the edges of space, it is now possible to define a long list
      of minerals and their weathering products detectable at these wavelengths. These
      include hydroxyl-bearing minerals such as hydrothermal clays, sulfates, ammonium
      bearing minerals, phyllosilicates, iron oxides, carbonates, and a wide range of
      silicates. Indeed, even the chemical composition of micas and chlorites has been
      mapped remotely using subtle wavelength shifts in their diagnostic reflectance
      spectra, indicating varying degrees of Na, K, Al, Mg and Fe substitution. Spatial
      zones, relative abundances and assemblages of these minerals allow geologists to
      reconstruct the mineralogical, chemical and sometimes thermal disposition of
      ancient hydrothermal systems in their search for optimal drilling targets. Such
      minerals not only result directly from the hydrothermal processes involved but
      may also 'expose' older host rocks caught up in the process and brought to the
      surface. New microwave radar systems are also shedding new light on landscape
      processes, textures and structure and occasionally penetrating dry surface layers
      to reveal buried structures.

PMID- 9243019
TI  - Exploration strategies for hydrothermal deposits.
AB  - With unlimited money the most certain strategy for finding most hydrothermal
      metal deposits would be by drilling to 5000 m at 50 m spacing. However, the cost
      would far outweigh the benefit of the discoveries. Geological knowledge and
      exploration techniques may be used to obtain the greatest benefit for minimum
      cost, and to concentrate human and material resources in the most economic way in
      areas with the highest probability of discovery. This paper reviews the economic
      theory of exploration based on expected value, and the application of geological
      concepts and exploration techniques to exploration for hydrothermal deposits.
      Exploration techniques for hydrothermal-systems on Mars would include
      geochemistry and particularly passive geophysical methods.

PMID- 9243020
TI  - Water on early Mars.
AB  - Large flood channels, valley networks and a variety of features attributed to the
      action of ground ice indicate that Mars emerged from heavy bombardment 3.8 Ga
      ago, with an inventory of water at the surface equivalent to at least a few
      hundred metres spread over the whole planet, as compared with 3 km for the Earth.
      The mantle of Mars is much drier than that of the Earth, possibly as a result of
      global melting at the end of accretion and the lack of plate tectonics to
      subsequently reintroduce water into the interior. The surface water resided
      primarily in a porous, kilometres-thick megaregolith created by the high impact
      rates. Under today's climatic conditions groundwater is trapped below a thick
      permafrost zone. At the end of heavy bombardment any permafrost zone would have
      been much thinner because of the high heat flows, but climatic conditions may
      have been very different then, as suggested by erosion rates 1000 times higher
      than subsequent rates. Water trapped below the permafrost periodically erupted
      onto the surface to form large flood channels and lakes. Given abundant water at
      the surface and sustained volcanism, hydrothermal activity must have frequently
      occurred but we have yet to make the appropriate observations to detect the
      results of such activity.

PMID- 9243021
TI  - Hydrothermal systems on Mars: an assessment of present evidence.
AB  - Hydrothermal processes have been suggested to explain a number of observations
      for Mars, including D/H ratios of water extracted from Martian meteorites, as a
      means for removing CO2 from the Martian atmosphere and sequestering it in the
      crust as carbonates, and as a possible origin for iron oxide-rich spectral units
      on the floors of some rifted basins (chasmata). There are numerous examples of
      Martian channels formed by discharges of subsurface water near potential magmatic
      heat sources, and hydrothermal processes have also been proposed as a mechanism
      for aquifer recharge needed to sustain long term erosion of sapping channels. The
      following geological settings have been identified as targets for ancient
      hydrothermal systems on Mars: channels located along the margins of impact crater
      melt sheets and on the slopes of ancient volcanoes; chaotic and fretted terranes
      where shallow subsurface heat sources are thought to have interacted with ground
      ice; and the floors of calderas and rifted basins (e.g. chasmata). On Earth, such
      geological environments are often a locus for hydrothermal mineralization. But we
      presently lack the mineralogical information needed for a definitive evaluation
      of hypotheses. A preferred tool for identifying minerals by remote sensing
      methods on Earth is high spatial resolution, hyperspectral, near-infrared
      spectroscopy, a technique that has been extensively developed by mineral
      explorationists. Future efforts to explore Mars for ancient hydrothermal systems
      would benefit from the application of methods developed by the mining industry to
      look for similar deposits on Earth. But Earth-based exploration models must be
      adapted to account for the large differences in the climatic and geological
      history of Mars. For example, it is likely that the early surface environment of
      Mars was cool, perhaps consistently below freezing, with the shallow portions of
      hydrothermal systems being dominated by magma-cryosphere interactions. Given the
      smaller gravitational field, declining atmospheric pressure, and widespread,
      permeable megaregolith on Mars, volatile outgassing and magmatic cooling would
      have been more effective than on Earth. Thus, hydrothermal systems are likely to
      have had much lower average surface temperatures than comparable geological
      settings on Earth. The likely predominance of basaltic crust on Mars suggests
      that hydrothermal fluids and associated deposits should be enriched in Fe, Mg, Si
      and Ca, with surficial deposits being dominated by lower temperature, mixed iron
      oxide and carbonate mineralogies.

PMID- 9243023
TI  - Nomenclature for aerobic and facultative bacteria.

PMID- 9243022
TI  - The transfer of viable microorganisms between planets.
AB  - There is increasing acceptance that catastrophic cosmic impacts have played an
      important role in shaping the history of terrestrial life. Large asteroid and
      cometary impacts are also capable of displacing substantial quantities of
      planetary surface material into space. The discovery of Martian rocks on Earth
      suggests that viable microorganisms within such ejecta could be exchanged between
      planets. If this conjecture is correct, it will have profound implications for
      the origin and evolution of life in the solar system.

PMID- 9243024
TI  - Microbiology terminology update: clinically significant anaerobic gram-positive
      and gram-negative bacteria (excluding spirochetes).

PMID- 9243025
TI  - Some medically important fungi and their common synonyms and obsolete names.

PMID- 9243026
TI  - Viral taxonomy.

PMID- 9243027
TI  - Classification of human parasites.

PMID- 9243028
TI  - Donovanosis.

PMID- 9243029
TI  - Photo quiz. Contact dermatitis secondary to Neosporin ointment.

PMID- 9243030
TI  - The emerging infections network: a new venture for the Infectious Diseases
      Society of America. Executive Committee of the Infectious Diseases Society of
      America Emerging Infections Network.
AB  - The Infectious Diseases Society of America (IDSA), in cooperation with the
      Centers for Disease Control and Prevention, has launched an Emerging Infections
      Network (EIN). This network of infectious diseases consultants was conceived as a
      sentinel system to monitor new or resurgent infectious diseases in a way that
      would complement other public health surveillance efforts. A pilot study with 169
      participants recruited from 32 of the IDSA's state and regional societies
      confirmed the feasibility and potential value of this network. More than 300
      infectious diseases consultants are currently participating in the IDSA EIN.
      Future plans include aggressive probing for clinical experiences that indicate or
      suggest the presence of emerging infections, initiation of prospective studies
      for selected infectious diseases, and other activities designed both to benefit
      consultants in infectious diseases and to make use of their services.

PMID- 9243031
TI  - Stage-specific manifestation of mold infections in bone marrow transplant
      recipients: risk factors and clinical significance of positive concentrated
      smears.
AB  - Potassium hydroxide-concentrated smears, prepared from sedimented remains of
      clinical specimens, were used to distinguish between mold infection and exogenous
      contamination in fungal culture-positive specimens. This method was applied in
      the study of 3,857 clinical specimens from 230 bone marrow transplant recipients
      who were followed up prospectively for infectious complications. Concentrated
      smears of only 86 (from 21 infected patients) of 149 fungal culture-positive
      specimens were positive for hyphae; 82 of the strains were Aspergillus species.
      Concentrated smears of the remaining 63 fungal culture-positive specimens were
      negative; the strains identified by culture were considered as exogenous
      contaminants (87% of which were Penicillium species). A stage-specific
      manifestation of mold infection was observed: 67% of mold infections occurred
      during acute graft-vs.-host disease (GVHD) a median of 47 days after
      transplantation, whereas 9% of mold infections occurred as rapidly fatal invasive
      disease before engraftment. Overall, of the 21 patients with mold infection, 17
      (81%) had invasive mold disease, and four (19%) had mold colonization of airways
      secondary to chronic GVHD after day 100. The significant risk factors for mold
      infection were total-body irradiation and grade 2-4 acute GVHD. Because of our
      high mortality rate (82%), the consideration of antimold prophylaxis for such
      patients may be warranted.

PMID- 9243032
TI  - International Conference for the Development of a Consensus on the Management and
      Prevention of Severe Candidal Infections.
AB  - Because of the rapidly increasing incidence of serious candidal infections, a
      consensus conference of 22 investigators from the United States, Europe, and
      Japan was held to discuss strategies for the prevention and treatment of deep
      organ infections caused by Candida species. Commonly asked questions concerning
      the management of candidal infections were selected for discussion by the
      participating investigators. Possible answers to the questions were developed by
      the investigators, who then voted anonymously for their preferences. In certain
      instances, unanimity or a strong consensus was the result. In all cases, the full
      spectrum of responses was recorded and is presented in this report. The forms of
      candidal infection addressed included candidemia, candiduria, hepatosplenic
      candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and
      candidal peritonitis. Prevention and treatment strategies were considered for
      patients who have undergone surgery, for neutropenic and nonneutropenic patients,
      and for patients who have undergone bone marrow and solid organ transplantation.
      The therapeutic roles of amphotericin B (standard and lipid formulations) and the
      azoles were considered.

PMID- 9243033
TI  - Can we agree on the treatment of candidiasis?

PMID- 9243035
TI  - Polyclonal staphylococcus endocarditis.
AB  - Coagulase-negative staphylococcus (CNS) is the most frequent cause of nosocomial
      bacteremia and prosthetic valve endocarditis. CNS bacteremia can be polyclonal.
      No data exist on the clonality of CNS causing endocarditis. We present a case of
      CNS aortic homograft endocarditis in which at least five different genotypes of
      CNS were identified in initial blood-culture isolates by genomic macrorestriction
      enzyme analysis and pulsed field gel electrophoresis. Since the polyclonality was
      accompanied by differences in antibiotic susceptibility, this observation may
      have important consequences for the treatment of CNS endocarditis. Because of the
      parallels in the pathogenesis of CNS prosthetic valve endocarditis and CNS
      infections of a variety of other prosthetic devices, it might also have
      consequences for CNS prosthetic device infections in general. We suggest that
      antibiotic susceptibility testing of just one blood-culture isolate may be
      insufficient.

PMID- 9243034
TI  - Antecedent antimicrobial use increases the risk of uncomplicated cystitis in
      young women.
AB  - To examine whether antecedent antimicrobial use influenced subsequent relative
      risk of urinary tract infection (UTI) in premenopausal women, data were analyzed
      from two cohorts of women observed prospectively for 6 months to determine risk
      factors for UTI. Using a Cox proportional hazards model to adjust for covariates,
      we found that 326 women in a University cohort and 425 women in a health
      maintenance organization cohort were at increased risks for UTI (2.57 [95%
      confidence interval (CI), 1.24-5.32] and 5.83 [95% CI, 3.17-10.70], respectively)
      if antimicrobials had been taken during the previous 15-28 days but not during
      the previous 3, 7, or 14 days. The increased risks were noted both for women
      whose antimicrobial use was for treatment of a previous UTI and for women who
      received antimicrobials for other illnesses. These results suggest that recent
      antimicrobial use increases a woman's risk of UTI, perhaps by altering the
      indigenous urogenital flora and predisposing to vaginal colonization with
      uropathogens.

PMID- 9243036
TI  - Polyclonal staphylococcus bacteremia.

PMID- 9243037
TI  - Early discharge of low-risk febrile neutropenic children and adolescents with
      cancer.
AB  - During the past decade, a relatively lower-risk patient population of febrile
      neutropenic children with cancer (over one-half of all these patients) has been
      identified. These patients can be safely discharged from the hospital before
      their absolute neutrophil count (ANC) exceeds 500/mm3. To evaluate the practice
      of early discharge of these patients, 580 consecutive episodes of chemotherapy
      induced febrile neutropenia in 253 children and adolescents with cancer between
      June 1992 and May 1995 were reviewed. Three hundred thirty episodes ended in
      discharge before the patient's ANC was > 500/mm3. Patients were characterized as
      being at relatively lower risk if they had sterile blood cultures, were afebrile
      for > 24 hours, appeared well, and were thought to have evidence of marrow
      recovery. Of the 330 episodes, only 21 (6%) were associated with admission for
      recurrent fever during the subsequent 7 days. In retrospect, in only six of these
      21 cases of readmission (or 2% of 330 episodes) was there evidence of bone marrow
      recovery, and none of the blood cultures were positive during the subsequent
      hospitalization. All patients who met low-risk criteria fared well during their
      second hospitalization. This early discharge strategy was safe and resulted in
      substantial cost savings.

PMID- 9243038
TI  - Leclercia adecarboxylata infections: case report and review.
AB  - Leclercia adecarboxylata has been rarely isolated from environmental and clinical
      specimens. On review of the world literature, we found two reports of L.
      adecarboxylata infection: one report described a patient with hepatic cirrhosis,
      and the other described a child dependent on total parenteral nutrition. L.
      adecarboxylata was isolated from five infected patients who were evaluated at our
      institution. Three patients had lower-extremity wound infections in which L.
      adecarboxylata was part of a mixed microbial growth. One patient had pneumonia
      due to multiple bacteria, including L. adecarboxylata, which were isolated from
      sputum. L. adecarboxylata was isolated from the blood of one patient with
      neutropenia and from the blood of the two patients reported in the literature.
      All patients except one had fever and leukocytosis. L. adecarboxylata isolates
      were susceptible to all the antimicrobials tested. L. adecarboxylata is most
      frequently isolated as part of a mixed microbial growth. Its role in these
      infections is not clear. However, the organism caused bacteremia in three
      patients.

PMID- 9243039
TI  - Central nervous system pneumocystosis in a patient with AIDS.
AB  - Extrapulmonary involvement with Pneumocystis carinii has been described in 0.5%
      2.5% of persons with AIDS. One hundred nine patients with AIDS and confirmed
      extrapulmonary pneumocystosis were identified, and seven of these patients
      (including our patients) had central nervous system (CNS) pneumocystosis. Of
      these seven patients, six had prior AIDS-related complications, and three had
      previous P. carinii pneumonia. Six patients had CNS symptoms, one of whom
      underwent a focal neurological examination. No cases were diagnosed before death.
      The involved sites were the cerebral cortex (2 patients), meninges (2), pituitary
      gland (1), putamen (1), and nonspecified locations (3). In two patients,
      organisms were seen around blood vessels, and in five patients there was
      concurrent neuropathology. In summary, CNS involvement with P. carinii usually
      occurs as a late complication of AIDS and probably represents hematogenous
      dissemination.

PMID- 9243040
TI  - Evaluation of the range of clinical presentations of herpes simplex encephalitis
      by using polymerase chain reaction assay of cerebrospinal fluid samples.
AB  - Detection of DNA from herpes simplex virus in cerebrospinal fluid (CSF) samples
      by polymerase chain reaction (PCR) analysis has been shown to be more sensitive
      and specific for the diagnosis of herpes simplex encephalitis than isolation of
      herpes simplex virus from biopsy specimens of brain tissue. Because of the
      invasiveness of brain biopsy, it has been suggested that PCR analysis of CSF may
      reveal a wider spectrum of the disease than has been previously recognized by
      brain biopsy studies. In this study, PCR assay of CSF samples obtained from 29,
      12, and 8 patients with focal, mild, and diffuse encephalitis, respectively, was
      performed. PCR assay was positive for 15 (51.7%) of 29 patients with focal
      encephalitis and three (25%) of 12 patients with mild encephalitis. The
      correlation between temporal abnormalities shown by electroencephalography,
      computed tomography of the brain, or cranial magnetic resonance imaging and a
      positive PCR assay was high. PCR analysis has revealed that atypical and less
      severe forms of encephalitis are caused by herpes simplex virus.

PMID- 9243041
TI  - Discontinuation of antimicrobial therapy for febrile, neutropenic children with
      cancer: a prospective study.
AB  - During a 2-year period, all children with cancer, neutropenia, and fever who were
      admitted to Hospital de Ninos Luis Calvo Mackenna (Santiago, Chile) were enrolled
      in a study of the safety of stopping antibiotic therapy on day 3 of treatment.
      Children who met predefined criteria for nonbacterial fever were randomized on
      day 3 to stop (group A) or continue (group B) antibiotic therapy. A total of 220
      children with cancer had 238 episodes of fever and neutropenia; 68 children with
      75 episodes met entry criteria for nonbacterial fever (group A, 36; group B, 39).
      Both groups were comparable in terms of age, gender, oncological disease,
      chemotherapy status, and initial neutrophil count. Resolution of symptoms
      occurred in 34 of 36 episodes in group A and 36 of 39 episodes in group B (P >
      .05). No deaths occurred, and bacterial superinfections were uncommon. For
      children with cancer as well as episodes of fever and neutropenia without an
      identifiable bacterial etiology at admission, stopping antibiotic therapy on day
      3 was safe and not associated with a higher risk of bacterial superinfections.

PMID- 9243042
TI  - Absence of detectable antibody in a patient infected with human immunodeficiency
      virus.
AB  - Infection with human immunodeficiency virus (HIV) is routinely and easily
      diagnosed with use of enzyme immunoassay (EIA) test kits. We describe an unusual
      patient who developed AIDS despite testing negative for antibodies to HIV 35
      times over a 4-year period. HIV infection was confirmed by the results of p24
      antigen assays and polymerase chain reaction amplification of proviral DNA.
      Sequence analysis of the virus demonstrated that it was closely related to a
      strain obtained from the patient's sexual partner. The explanation for this
      patient's persistently negative EIA results is unclear. However, this case does
      suggest that physicians who treat patients with AIDS-defining conditions but for
      whom standard HIV antibody testing is negative should consider the possibility
      that HIV infection is present and may be identified by additional testing
      procedures.

PMID- 9243043
TI  - Serological screening tests for antibody to human immunodeficiency virus--the
      search for perfection in an imperfect world.

PMID- 9243044
TI  - Pharmacokinetics of antimycobacterial drugs in patients with tuberculosis, AIDS,
      and diarrhea.
AB  - To test the hypothesis that antituberculous drug disposition is altered in
      patients with AIDS, we studied the steady-state pharmacokinetics of isoniazid
      (300 mg/d), rifampin (600 mg/d), and pyrazinamide (1,500 mg/d) in 29 adults (14
      patients infected with human immunodeficiency virus [HIV] and 15 non-HIV-infected
      patients) with tuberculosis in Nairobi, Kenya. Intestinal integrity was assessed
      with xylose. Neither HIV infection nor diarrhea accounted for the interpatient
      variability in the area-under-the-plasma concentration vs. time curve (AUC), the
      maximum concentration, or the terminal half-life (t1/2) of isoniazid, rifampin,
      and pyrazinamide. No significant association between HIV infection or diarrhea
      and pharmacokinetics was seen for any of the compounds. In addition, neither the
      AUC nor the t1/2 of any of these drugs reflected interpatient differences in CD4
      lymphocyte counts. Xylose absorption was uniformly low. We did not demonstrate
      that HIV infection, diarrhea, or CD4 lymphocyte counts contributed significantly
      to the variability in pharmacokinetics of isoniazid, rifampin, and pyrazinamide
      in TB patients in Nairobi.

PMID- 9243045
TI  - Antimicrobial dosing in obese patients.
AB  - Although the dose of some drugs is commonly adjusted for weight, weight-related
      dosage adjustments are rarely made for most antimicrobials. We reviewed the
      English-language literature on antimicrobial pharmacokinetics and dosing in
      obesity. Although there are many potential pharmacokinetic consequences of
      obesity, the actual effect on the pharmacokinetics and clinical efficacy of most
      antimicrobials is unknown. Since approximately 30% of adipose is water, an
      empirical approach is use of the Devine formula to calculate ideal body weight
      (IBW), to which is added a dosing weight correction factor (DWCF) of 0.3 times
      the difference between actual body weight (ABW) and IBW (IBW + 0.3 x [ABW-IBW])
      to arrive at a weight on which to base dosage of hydrophilic antibiotics. No
      studies confirm this approach for beta-lactam drugs. Clinical studies suggest a
      DWCF of approximately 0.40 for aminoglycosides and 0.45 for quinolones. Final
      dosage adjustments for antimicrobials with a narrow toxic-therapeutic window
      should be based on serum concentrations.

PMID- 9243046
TI  - Concepts of fever: recent advances and lingering dogma.
AB  - Fever has been a preoccupation of clinicians since medicine's beginning. One
      might therefore expect that basic concepts relating to this physiological
      response would be well delineated and that such concepts would be widely known.
      In fact, only in the past several decades has the febrile response been subjected
      to scientific scrutiny. As a result of recent scientific investigation, modern
      concepts have evolved from a perception of fever as nothing more than a rise in
      core temperature to one in which fever is recognized as a complex physiological
      response characterized by a cytokine-mediated rise in temperature, as well as by
      generation of acute-phase reactants and activation of a panoply of physiological,
      endocrinologic, and immunologic systems. The average clinician appears to have
      little more than a regrettably rudimentary knowledge of these modern concepts of
      fever. This symposium summary considers many such concepts that have immediate
      relevance to the practice of medicine.

PMID- 9243047
TI  - A focus of tick-borne relapsing fever in southern Zaire.
AB  - Relapsing fevers occur worldwide and are characterized by recurrent episodes of
      fever and spirochetemia. In central, eastern, and southern Africa, the disease is
      often caused by Borrelia duttonii, which is transmitted by the soft tick
      Ornithodors moubata. We conducted a field investigation in September 1994 at a
      hospital in Mitwaba, southern Zaire, which was the only medical facility within
      150 km. The introduction of a rapid blood-smear staining technique allowed us to
      demonstrate that 4.3%-7.4% of the 25-50 new outpatients seen each day had
      relapsing fever. Because of the absence of malaria in this area, these patients
      account for most of the febrile patients. The incidence of relapsing fever among
      all pregnant women in the maternity ward was estimated to be 6.4%, and this
      condition often led to maternal death or to spontaneous abortion. The 16S rRNA
      gene of B. dutonii was sequenced after the spirochete was isolated from patients'
      blood samples and directly from Ornithodoros tick vectors. In this region of
      Africa, relapsing fever should now be considered an important public health
      priority.

PMID- 9243048
TI  - Pyomyositis of the anterior tibial compartment.
AB  - Five oncology patients developed bacterial pyomyositis involving the anterior
      tibial compartment and resulting in compartment syndrome with ischemia and
      abnormalities of neuromuscular function. All patients were neutropenic and
      thrombocytopenic, and four were receiving or had recently received cancer
      chemotherapy. Three infections were due to gram-negative bacilli and two to
      Staphylococcus aureus. Appropriate antimicrobial therapy and surgical drainage in
      four patients resulted in the resolution of these infections with good residual
      muscle function. To our knowledge, primary pyomyositis has never previously been
      known to cause compartment syndrome.

PMID- 9243049
TI  - Minocycline and ethylenediaminetetraacetate for the prevention of recurrent
      vascular catheter infections.
AB  - Three patients with recurrent vascular catheter-related bacteremia were
      successfully treated by allowing a solution of minocycline and
      ethylenediaminetetraacetate (EDTA) to dwell in the lumen of the indwelling
      catheter or by coating polyurethane catheters with minocycline/EDTA and flushing
      the lumen daily with the same solution. In vitro and in vivo experiments showed
      that minocycline/EDTA may have broad-spectrum antimicrobial activity, may have
      optimal anticoagulant activity, and may be highly efficacious in preventing
      catheter colonization.

PMID- 9243050
TI  - Liver abscess caused by Capnocytophaga species.

PMID- 9243051
TI  - Invasive disease due to Epidermophyton floccosum in an immunocompromised patient
      with Behcet's syndrome.

PMID- 9243052
TI  - Leukocytoclastic vasculitis and polyarthritis associated with Mycoplasma
      pneumoniae infection.

PMID- 9243053
TI  - Failure to clear a Roseomonas line infection with antibiotic therapy.

PMID- 9243054
TI  - Severe reversible reticulocytopenic anemia associated with
      quinupristin/dalfopristin RP59500 therapy.

PMID- 9243055
TI  - Clostridium difficile--associated diseases: comparison of symptomatic infection
      versus carriage on the basis of risk factors, toxin production, and genotyping
      results.

PMID- 9243056
TI  - Right-sided pacemaker-related endocarditis due to Acremonium species.

PMID- 9243057
TI  - Pleural empyema due to Clostridium difficile and Clostridium cadaveris.

PMID- 9243058
TI  - Candida inconspicua, a fluconazole-resistant pathogen in patients infected with
      human immunodeficiency virus.

PMID- 9243059
TI  - Therapy with RP 59500 (quinupristin/dalfopristin) for prosthetic valve
      endocarditis due to enterococci with VanA/VanB resistance patterns.

PMID- 9243060
TI  - First case report of melioidosis in Guadeloupe, a French West Indies archipelago.

PMID- 9243061
TI  - Prevalence of hepatitis G virus among intravenous drug abusers in Los Angeles.

PMID- 9243062
TI  - Measurement of fecal lactoferrin for rapid diagnosis of enterohemorrhagic
      Escherichia coli infection.

PMID- 9243063
TI  - Therapy for severe community-acquired pneumonia.

PMID- 9243064
TI  - Echo-guided diagnosis and treatment of hepatic hydatid cysts.

PMID- 9243065
TI  - Treatment of human immunodeficiency virus-related thrombocytopenia with
      intravenous anti-rhesus D immunoglobulin.

PMID- 9243066
TI  - Salmonella urinary tract infections associated with exposure to pet iguanas.

PMID- 9243067
TI  - Imaging input technology.
AB  - Imaging input technology is at its greatest rate of development ever, with CCD
      technology improving both in terms of image quality and image economy. The
      current diversity of imager modalities and application specializations allows for
      elegant matching of device capability to image subject photographic requirements.
      Both color and low-light imaging technologies continue to evolve, with ever
      increasing resolution and dynamic range. The "order of magnitude" cost decreases
      that so aptly characterized the computer industry of the 1970s and 1980s is now
      upon the digital imager industry. Although analog cameras, based on video
      formats, still prevail, the direct digital camera will emerge as the preferred
      input device within a decade.

PMID- 9243068
TI  - Image output technology.
AB  - Once an image has been captured and stored, whether it is in analog or digital
      format, for it to be useful in the future there must exist some way of re
      rendering it. It is hoped this will be in a manner that is imperceptibly
      different from the original. Because it is usually impossible to render an image
      in identical form to the original, numerous decisions need to be made concerning
      which attributes are the most important, in terms of image archival quality and
      diagnostic accuracy.

PMID- 9243069
TI  - Optical considerations in digital imaging.
AB  - The topic of optics and its effect in ultimate rendered image quality has largely
      been underemphasized for medical imaging systems. In actuality, adequate
      attention to optical issues is essential in ensuring that image quality is
      optimal. Generally, optical issues can be divided into two broad categories:
      optical interface optimization and lighting optimization. Although these issues
      deal with disparate aspects of optical physics, they are covered within a single
      article because they both apply to the common goal of generating superior medical
      images.

PMID- 9243070
TI  - The pathologist's workstation.
AB  - To leverage the time and expertise of the pathologist, a comprehensive
      workstation is a useful tool. Because the practice of pathology is so diverse,
      however, there is no one standard for what constitutes a workstation. The author
      reviews the several elements and components which must be included (access to
      your LIS, word processing, electronic mail, Web browser, literature search), and
      also reviewed are the many more which may be included, depending on the
      specialized needs of the practitioner (statistical analysis, ROC curves, image
      analysis, voice synthesis). It is, however, up to the pathologist to determine
      which of these components are required and to assemble them in as seamless a
      manner as possible.

PMID- 9243071
TI  - Digital imaging as a teaching tool for pathologists.
AB  - Digital Imaging is a technology which should be of considerable interest to
      pathologists as the use of gross and microscopic pathology images plays an
      important part in their role as medical educators. Digital imaging may have
      important advantages over conventional film photography which can be exploited by
      the pathologist to create all-digital presentations. In this article, the basic
      components of digital imaging are described, along with an affordable and
      practical approach which should allow most pathologists to begin to explore this
      medium.

PMID- 9243072
TI  - Telemedicine and telepathology.
AB  - Telepathology is entering a golden era in which both the technology and the
      rationale for utilizing this technology are evolving. The following decade will
      see the introduction of national and international telepathology networks,
      founded on the principle of improving patient care and increasing cost
      effectiveness. As telecommunications and imaging technology concurrently advance,
      newer generations of telepathology platforms will ultimately deliver performance
      that will be essentially indistinguishable from that of microscope-derived
      diagnoses.

PMID- 9243073
TI  - Computerized scanning devices for Pap smear screening: current status and
      critical review.
AB  - Automation of the Pap smear has taken almost half of a century. Two systems have
      recently received FDA approval for routine use as quality control (rescreening)
      devices. Technical triumphs are overshadowed by current conflicts among
      cytopathology professionals, clinicians, patients, and device manufacturers. The
      historic perspective of this potentially volatile situation provides the backdrop
      for possible solutions based on the scientific validity of this evolving
      technology.

PMID- 9243074
TI  - Digital image processing for microscopy.
AB  - The author introduces some of the basic concepts in the theory and mechanics of
      digital signal processing techniques as applied to microscopy. With the right
      software and a sound approach, a great deal of information can be retrieved from
      noisy or degraded images. The author also discusses manipulation of images in
      order to produce a clearer images for the observer.

PMID- 9243075
TI  - Specialized imaging techniques.
AB  - The foregoing discussion has presented a summary of many of the optical
      microscopic methods in use by researchers and clinicians. Along with emerging
      technologies, such as laser tweezers and scissors, which are outside the scope of
      this review, the methodologies discussed here ensure that the optical microscope
      will remain a central tool for biomedical research.

PMID- 9243076
TI  - Digital imaging standards and system interoperability.
AB  - Standards development in medical imaging originated in the field of radiology and
      has rapidly spread to numerous other medical specialties. Pathology is well
      represented in this effort, and it benefits from interoperability made possible
      by the utilization of the DICOM 3.0 standard in the fabrication of pathology
      workstations. Because there currently exists a strong trend for both standards
      convergence and international harmonization, the formation of a world-wide
      electronic medical image standard is likely only several years away.

PMID- 9243077
TI  - Heart failure 1997: a time to take stock.

PMID- 9243078
TI  - The role of cytokines in disease progression in heart failure.
AB  - Recent studies have identified the importance of biologically active molecules
      such as neurohormones as mediators of disease progression in heart failure. More
      recently it has become apparent that in addition to neurohormones, another
      portfolio of biologically active molecules, termed cytokines, are also expressed
      in the setting of heart failure. This article reviews recent clinical and
      experimental material that suggests that the cytokines, much like the
      neurohormones, may represent another class of biologically active molecules that
      are responsible for the development and progression of heart failure.

PMID- 9243079
TI  - Mechanisms of exercise intolerance in congestive heart failure.
AB  - A major aim in treating patients with chronic heart failure is to improve
      exercise capacity and quality of life. Experimental evidence does not support the
      view that central hemodynamic disturbance is the sole determinant of exercise
      capacity. Rather, multiple other factors including abnormalities of ventilatory
      control, the lungs, the peripheral circulation, and skeletal muscle appear to
      combine to generate symptoms and limit exercise.

PMID- 9243080
TI  - Update on digoxin and other oral positive inotropic agents for chronic heart
      failure.
AB  - The benefit of digoxin in chronic heart failure has been debated fervently for
      decades. In the 1970s, the use of digoxin was challenged due to the high
      incidences of digitalis toxicity and the lack of data on the effects of digoxin
      in patients with chronic heart failure. In the 1980s, interest in digoxin was
      renewed after several trials with oral inotropic agents demonstrated increased
      mortality. Recently, several trials have studied the hemodynamic, neurohormonal,
      and clinical effects of digoxin, providing further insights into the possible
      mechanisms for its beneficial effects in patients with chronic heart failure. In
      an effort to find new pharmacologic therapies for the treatment of this patient
      population, studies of newer oral inotropic agents such as vesnarinone,
      pimobendan, and ibopamine have been disappointing. This paper reviews data
      published or presented in 1995 and 1996 examining the effects of digoxin and
      other oral inotropic agents in patients with chronic heart failure.

PMID- 9243081
TI  - Pharmacologic and nonpharmacologic treatment of ventricular arrhythmias in heart
      failure.
AB  - Ventricular arrhythmias are common in patients with heart failure. The risk and
      benefits of antiarrhythmic therapies continue to be defined. Class I
      antiarrhythmic drugs should be avoided due to proarrhythmic and negative
      inotropic effects that may be responsible for increased mortality in some trials.
      For patients resuscitated from sustained ventricular tachycardia or ventricular
      fibrillation, amiodarone or an implantable cardioverter-defibrillator should be
      considered. Implantable cardioverter-defibrillators markedly reduce sudden death
      in ventricular tachycardia and ventricular fibrillation survivors, but in
      advanced heart failure, this may not markedly extend survival. Catheter or
      surgical ablation can be considered for selected patients with bundle branch
      reentry ventricular tachycardia or difficult to control monomorphic ventricular
      tachycardia. For patients who have not had sustained ventricular tachycardia or
      ventricular fibrillation antiarrhythmic therapy should generally be avoided, but
      may benefit some high risk patients. Amiodarone may be beneficial in patients
      with advanced heart failure and rapid resting heart rates. Implantable
      cardioverter-defibrillators may improve survival in selected patients with
      depressed ventricular function after myocardial infarction, who also have
      nonsustained and inducible ventricular tachycardia.

PMID- 9243082
TI  - Mechanisms and management of renal dysfunction in heart failure.
AB  - The syndrome of congestive heart failure is characterized by activation of many
      neurohormonal systems with vasoconstrictor and vasodilator actions. Data suggest
      that the stimulus that evokes this response is a threat to the arterial blood
      pressure. The long-term consequences of this response on the kidney are retention
      of sodium and water. Strategies designed to reverse the effects of these
      neurohormones on the kidney have so far had limited success.

PMID- 9243083
TI  - Mechanisms and implications of endothelial dysfunction in congestive heart
      failure.
AB  - The pathogenesis of heart failure is determined by the ventricular and vascular
      responses to myocellular injury. Experimental and clinical studies suggest that
      the vascular endothelium may play an important role in modulating progression of
      ventricular and vascular remodeling in heart failure. Endothelial cell
      dysfunction has been described in the coronary and skeletal muscle circulations
      of patients with heart failure and appears to be characterized by decreased
      endothelial synthesis of nitric oxide and increased production of endothelin-1.
      The pathogenesis of endothelial dysfunction in heart failure is unknown, but may
      be related to increased oxidative stress, abnormal regional flow conditions, and
      cytokine and neurohormonal activation. The specific role of endothelial
      dysfunction in the pathogenesis of heart failure remains to be determined. If
      endothelial dysfunction does contribute to progression of disease in early heart
      failure, specific therapies to enhance endothelial dysfunction may improve long
      term morbidity and mortality.

PMID- 9243084
TI  - Mechanisms and implications of autonomic nervous system dysfunction in heart
      failure.
AB  - Neurohumoral activation characterizes heart failure. Patients with the greatest
      amount of neurohumoral activation, as estimated by plasma norepinephrine levels,
      have the worst prognosis. The fundamental mechanisms underlying this neurohumoral
      activation remain unknown, however. Recent data support the hypothesis that early
      sympathetic dysregulation in heart failure is attributable to early attenuation
      of cardiac and arterial baroreceptor control of sympathetic nerve activity.
      Neurohumoral excitation is organ specific, affecting the heart first.
      Neurohumoral activation follows a stepwise pattern, with resistance to atrial
      natriuretic peptide and marked sympathetic activation characterizing a transition
      period from left ventricular dysfunction to overt heart failure. Renin
      angiotensin-aldosterone system activation then occurs. Additional abnormalities
      of afferent systems, such as augmented muscle metaboreceptor sensitivity and
      increased peripheral chemoreceptor sensitivity, may modulate the sympathetic
      activation in established heart failure. Brain ouabainlike activity has been
      shown to cause sympathetic excitation in two animal models of heart failure and
      may play a key (although presently undefined) role in neurohumoral excitation in
      humans with heart failure. Therapies that interrupt, or even reverse, the
      neurohumoral activation in heart failure hold the greatest promise for the
      growing patient population afflicted with this syndrome.

PMID- 9243085
TI  - Anticoagulant and antiplatelet therapy in heart failure.

PMID- 9243086
TI  - Basic elements of gene mapping and identification.
AB  - The Human Genome Project has vastly facilitated the localization, identification,
      and characterization of disease-related genes by means of positional cloning.
      Application of this technique has elucidated the pathophysiology of several
      inheritable cardiovascular disorders and will ultimately change the clinical
      evaluation of and approach to these diseases. Over the next several years,
      efforts aimed at gene identification, DNA sequencing, correlation of genetic and
      physical maps, and manipulation of large segments of DNA will lead to
      identification of numerous candidate genes for positional analysis and will
      provide ample opportunity to identify the genetic abnormalities in other
      cardiovascular disorders. Because of the importance and clinical implications of
      these advances, a conceptual understanding of this methodology is essential to
      the practicing clinician.

PMID- 9243087
TI  - The molecular genetics of hypertrophic cardiomyopathy.
AB  - The study of hypertrophic cardiomyopathy has been at the vanguard of molecular
      genetic investigation into inherited diseases of the cardiovascular system for
      the greater part of the last decade. These studies have shown it to be a disease
      of sarcomeric contractile proteins and have highlighted its genetic
      heterogeneity. There are now seven known genetic loci and six disease genes
      associated with the condition. The biology of the mutant polypeptides has been
      studied in vitro, and animal models are being developed. Increased understanding
      gained from these studies has clarified features of the condition at the clinical
      level and has had an impact on management of patients. It is hoped that this work
      will lead to the development of novel therapies for both hypertrophic
      cardiomyopathy and acquired forms of left ventricular hypertrophy.

PMID- 9243088
TI  - Molecular genetics of dilated cardiomyopathy.
AB  - A major advance in the study of the pathogenesis of dilated cardiomyopathy (DC)
      has been the identification of a familial trait in a relevant proportion of cases
      (more than 25%), which indicates that, at least in these cases, a mutated gene is
      the cause of the disease. Familial dilated cardiomyopathy is a genetically
      heterogeneous disorder, most frequently with autosomal-dominant inheritance. Five
      different loci that cosegregate with the disease have been mapped so far; the
      identification of the disease genes is still in progress. The only disease gene
      known so far is the dystrophin gene, which causes X-linked DC. By analogy with
      dystrophin, it is believed that other cytoskeletal proteins could be involved in
      the pathogenesis of DC. Finally, in right ventricular cardiomyopathy, a peculiar
      form of cardiomyopathy that is frequently familial as well, several disease loci
      have been described. Also in this case, no disease gene has been yet identified.
      The advances in clinical and molecular genetics of DC have relevant clinical and
      therapeutic implications.

PMID- 9243089
TI  - Molecular genetics of long QT syndrome from genes to patients.
AB  - Recently, there has been intense excitement in the field of cardiac arrhythmias.
      Molecular genetic studies have led to significant progress in characterizing
      molecular mechanisms underlying long QT syndrome, an inherited cardiac disorder
      that causes syncope, seizures, and sudden death from ventricular arrhythmias.
      Three long QT syndrome genes have been identified: SCN5A on 3p21-24, HERG on 7q35
      36, and KVLQT1 on 11p15.5; all encode cardiac mycote ion channels. Molecular and
      electrophysiological characterization of these three long QT syndrome genes has
      led to identification of three critical electrical currents in the human heart
      (INa, IKr, IKa) and provides insight into our fundamental understanding of
      cardiac function. Genetic testing and gene-specific therapies are now available
      for some families with long QT syndrome.

PMID- 9243090
TI  - Molecular genetics of congenital heart disease.
AB  - This review of advances made toward understanding the molecular basis of
      congenital heart disease covers studies on subjects ranging from atrioventricular
      septal defects to zebrafish models. Genetically abnormal mice with
      atrioventricular septal defects have abnormal endocardial cushion development
      with the delayed appearance of mesenchymal cells and certain critical adhesion
      proteins. The prevalence of 22q11 deletions among patients with the conotruncal
      defects was estimated at 8% to 17%. Deletions were rare among patients lacking
      typical DiGeorge syndrome (DGS) or velocardiofacial (VCF) dysmorphic features,
      and more common in tetralogy of Fallot with pulmonary atresia than tetralogy of
      Fallot alone. Studies with patients with unusual 22q11 defects revealed that
      regional effects on several genes seem to underlie these complex phenotypes. A
      second DGS/VCF region on chromosome 10p13 was defined molecularly. Laterality
      defects (heterotaxy) have been associated with connexin43 mutations, and mice
      lacking connexin43 developed pulmonary atresia with intact ventricular septum.
      Three other groups failed to find connexin43 mutations in heterotaxy patients,
      suggesting genetic heterogeneity. Studies of cardiac looping with lower
      vertebrates revealed the critical role of the notochord. Ellis-van Creveld
      syndrome, an autosomal dominant skeletal dysplasia with atrial septal defects,
      and familial total anomalous pulmonary venous return, an autosomal dominant trait
      with reduced penetrance, were genetically linked to chromosomal bands 4p16 and
      4p13-q12, respectively. The zebrafish has emerged as an important model for the
      study of the earliest stages of the cardiovascular system, and the miles apart
      and gridlock mutants, which have failure of heart tube fusion and aortic atresia,
      respectively, are discussed.

PMID- 9243092
TI  - Cardiac failure.

PMID- 9243091
TI  - Dystrophies and heart disease.
AB  - The muscular dystrophies are a clinically and genetically heterogeneous group of
      skeletal muscle-wasting diseases that differ widely in their frequency and
      pattern of cardiac involvement. Myocardial disease manifesting predominantly as
      cardiomyopathy and congestive heart failure is characteristic of Duchenne and
      Becker muscular dystrophies and X-linked dilated cardiomyopathy, whereas
      conduction system abnormalities that cause heart block, arrhythmias, and sudden
      death are more commonly seen in limb-girdle type 1B, myotonic, and Emery-Dreifuss
      muscular dystrophies. Primary defects in the mechanical stabilization of the
      plasma membrane and signal transduction may underlie these two groups of muscular
      dystrophies. The identification of several new disease genes has yielded
      additional insights into the pathophysiology of muscular dystrophy. Molecular
      genetic and biochemical analyses of patient samples now permit accurate diagnosis
      and genotype-phenotype correlations. Ultimately, this knowledge will provide the
      foundation for etiology-specific gene therapy.

PMID- 9243093
TI  - Molecular genetics.

PMID- 9243094
TI  - Renal glucose production and utilization: new aspects in humans.
AB  - According to current textbook wisdom the liver is the exclusive site of glucose
      production in humans in the postabsorptive state. Although many animal and in
      vitro data have documented that the kidney is capable of gluconeogenesis,
      production of glucose by the human kidney in the postabsorptive state has
      generally been regarded as negligible. This traditional view is based on net
      balance measurements which, other than after a prolonged fast or during metabolic
      acidosis, showed no significant net renal glucose release. However, recent
      studies have refuted this view by combining isotopic and balance techniques,
      which have demonstrated that renal glucose production accounts for 25% of
      systemic glucose production. Moreover, these studies indicate that glucose
      production by the human kidney is stimulated by epinephrine, inhibited by insulin
      and is excessive in diabetes mellitus. Since renal glucose release is largely, if
      not exclusively, due to gluconeogenesis, it is likely that the kidney is as
      important a gluconeogenic organ as the liver. The most important renal
      gluconeogenic precursors appear to be lactate, glutamine and glycerol. The
      implications of these recent findings on the understanding of the physiology and
      pathophysiology of human glucose metabolism are discussed.

PMID- 9243095
TI  - Effect of feeding, fasting, and diabetes on liver glycogen synthase activity,
      protein, and mRNA in rats.
AB  - Hepatic glycogen synthase activity is increased in diabetic animals. However, the
      relationship between enzymic activity, enzyme protein mass, and mRNA abundance
      has not been well characterized. In the present study, these relationships were
      determined in 3- and 8-day diabetic, fed and fasted rats. The results were
      compared to data obtained in normal fed and fasted animals. In normal rats, total
      synthase specific activity and protein mass were similar in the fed and fasted
      state. However, in fed animals, the synthase mRNA abundance was increased 1.7
      fold. In 3-day diabetic rats, total synthase specific activity was increased
      approximately 29% compared to normal controls. It was unaffected by feeding and
      fasting and was associated with an approximate 15% increase in enzyme mass.
      Synthase mRNA was increased 1.8 and 2.6-fold in fasted and fed animals,
      respectively. In 8-day diabetic rats, total synthase specific activity was
      increased more than 2-fold compared to controls. However, the enzyme protein mass
      was decreased by approximately 20%. The mRNA abundance in 8-day diabetic fasted
      rats was only 30% of controls, while in fed rats it was increased by 40%. These
      data indicate that feeding and fasting have a major effect on synthase mRNA
      abundance which is independent of synthase activity, or protein mass, or both, in
      normal and diabetic animals. Total synthase specific activity increased with
      duration of diabetes. This was associated with only a modest change in protein
      mass. Thus, diabetes induces an increase in synthase catalytic efficacy. The
      specific activity of phosphorylase is decreased in diabetic rats.

PMID- 9243096
TI  - The relationship between accumulation of advanced glycation end products and
      expression of vascular endothelial growth factor in human diabetic retinas.
AB  - Both advanced glycation end products and vascular endothelial growth factor are
      believed to play a role in the pathogenesis of diabetic retinopathy. It is known
      that vascular endothelial growth factor causes retinal neovascularization and a
      breakdown of the blood-retinal barrier; how advanced glycation end products
      affect the retina, however, remains largely unclear. The substance-Ne
      (carboxymethyl)lysine is a major immunologic epitope, i.e. a dominant advanced
      glycation end products antigen. We generated an anti-Ne-(carboxymethyl)lysine
      antibody to investigate the relationship between the localization of advanced
      glycation end products and that of vascular endothelial growth factor in 27 human
      diabetic retinas by immunohistochemistry. Nine control retinas were also
      examined. In all 27 diabetic retinas, Ne-(carboxymethyl)lysine was located in the
      thickened vascular wall. In 19 of the 27 retinas, strand-shaped Ne
      (carboxymethyl)lysine immunoreactivity was also observed around the vessels. In
      all 27 diabetic retinas, vascular endothelial growth factor revealed a
      distribution pattern similar to that of Ne-(carboxymethyl)lysine. Vascular
      endothelial growth factor was also located in the vascular wall and in the
      perivascular area. Neither Ne-(carboxymethyl)lysine nor vascular endothelial
      growth factor immunoreactivity was detected in the 9 control retinas. Vessels
      with positive immunoreactivity for Ne-(carboxymethyl)lysine and/or vascular
      endothelial growth factor were counted. A general association was noted between
      accumulation of Ne-(carboxymethyl)lysine and expression of vascular endothelial
      growth factor in the eyes with non-proliferative diabetic retinopathy (p < 0.01)
      and proliferative diabetic retinopathy (p < 0.05).

PMID- 9243097
TI  - Effects of angiotensin II on insulin receptor binding and mRNA levels in normal
      and diabetic rats.
AB  - Both the density and level of mRNA encoding insulin receptors in the kidney are
      inversely related to the dietary sodium content, suggesting a feedback mechanism
      that limits the insulin-induced sodium retention when extracellular fluid volume
      is expanded. Because angiotensin II affects tissue sensitivity to insulin in
      humans, we investigated whether angiotensin II affects insulin receptor binding
      and mRNA levels in the kidney, liver, and renal arteries of normal rats and rats
      with streptozotocin-induced diabetes mellitus. Non-diabetic and diabetic rats
      were infused for 7 days with either vehicle or angiotensin II at a rate of 200
      ng. kg-1. min-1. In a separate experiment, normal rats were treated with an
      angiotensin converting enzyme inhibitor (captopril, 100 mg/dl in the drinking
      water) or vehicle for 7 days. Regional analysis of insulin receptor binding in
      the kidney and renal arteries was performed by an in situ technique using
      computerized microdensitometry and emulsion autoradiography. Insulin receptor
      mRNA levels were determined in renal and hepatic tissue by Northern blot
      hybridization and normalized with 28S rRNA. No differences in blood pressure were
      observed among diabetic and non-diabetic rats infused with either vehicle or
      angiotensin II, whereas captopril-treated rats had significantly lower blood
      pressure levels than their respective controls. Angiotensin II significantly
      decreased plasma renin concentration in both non-diabetic and diabetic rats.
      Insulin receptor number was significantly greater in the renal cortex of diabetic
      rats than in non-diabetics, whereas no significant differences were found in the
      outer medulla, inner medulla, or renal arteries. Angiotensin II infusion did not
      affect either the number or affinity of insulin receptors in any of the renal
      regions studied. Insulin receptor mRNA levels were significantly greater in the
      kidney and liver of diabetic rats than in non-diabetics and were not affected by
      angiotensin II infusion. Similar to angiotensin II infusion, captopril treatment
      did not affect either renal insulin receptor binding or mRNA levels. Thus,
      diabetic rats have increased insulin receptor binding and mRNA levels in
      comparison to non-diabetic rats. Angiotensin II infusion and captopril treatment
      do not affect insulin receptor binding and mRNA levels in the kidney, arguing
      against a role for this peptide in the modulation of renal sensitivity to
      insulin.

PMID- 9243098
TI  - Increased epidermal growth factor in experimental diabetes related kidney growth
      in rats.
AB  - Renal enlargement is a characteristic feature of human and experimental diabetes
      mellitus that may be predictive of subsequent nephropathy. In the streptozotocin
      diabetic rat kidney growth rapidly follows the induction of experimental diabetes
      but the mechanisms responsible for this growth are poorly understood. Epidermal
      growth factor (EGF) is a potent mitogen for renal tubular cells. Thirty one male
      Sprague-Dawley rats aged 13 weeks were randomised to receive either
      streptozotocin (diabetic, n = 20) or buffer (control, n = 11). Animals were
      studied on days 1, 3, 5 and 7 following streptozotocin. Diabetes was associated
      with a 3-fold increase in urinary EGF excretion (223 +/- 15 vs 59 +/- 5 ng/day,
      mean +/- SEM, diabetic vs control, p < 0.0001) and 3-6 fold increase in renal EGF
      mRNA relative to controls (p < 0.001). A transient rise in kidney EGF protein was
      noted on day 1. There was no difference between diabetic and control animals with
      regard to intrarenal sites of EGF expression or in plasma EGF. These data suggest
      that the increased urinary EGF excretion in diabetic animals is the result of
      enhanced local production and that EGF is not stored for a prolonged period
      within renal tubular cells but is released following its synthesis. In the
      context of the known intrarenal actions of EGF this growth factor may play a role
      in the pathogenesis of diabetes related kidney growth.

PMID- 9243099
TI  - The lymphopenia (lyp) gene controls the intrathymic cytokine ratio in congenic
      BioBreeding rats.
AB  - The lymphopenia gene (lyp) on rat chromosome 4 is closely linked to autoimmune
      diabetes in the BioBreeding (BB) rat. Lyp controls the number of peripheral
      lymphocytes by reducing T cells of the RT6+ phenotype by almost 90%. Following
      nine cycle of marker-assisted cross-intercross breeding we have developed
      congenic lyp/lyp, lyp/+ and +/+ (wildtype) rats on the background of DR rats.
      Prediabetic and insulitis free lyp/lyp, lyp/+ and +/+ rats were used to determine
      the effect of lyp on cytokine expression in the thymus. In situ hybridization of
      thymus cryosections showed that the interferon gamma (IFN gamma) mRNA expression
      was highest in lyp/lyp rats and the hybridization signal was restricted to the
      medullary compartment. The frequency of IFN gamma and interleukin (IL)-10 mRNA
      expressing cells in isolated thymocytes determined by quantitative image
      analysis, demonstrated an increased IFN gamma: IL-10 ratio in thymocytes from
      lyp/lyp homozygotes compared to lyp/+ and +/+ rats. This confirmed a lyp gene
      dose-dependent segregation of the IFN gamma high phenotype. Recombinant human
      glutamic acid decarboxylase (GAD65) increased the number of IFN gamma and IL-10
      mRNA expressing thymocytes after in vitro culture. We conclude that the
      quantitative ratio of cytokine producing thymocytes is associated with the lyp
      genotype. These potentially autoreactive thymocytes may explain the establishment
      of beta-cell directed autoimmunity in the BB rat despite peripheral lymphopenia.

PMID- 9243101
TI  - Quantitative morphology of the rat kidney during diabetes mellitus and insulin
      treatment.
AB  - A morphometric study was performed on moderately hyperglycaemic streptozotocin
      diabetic rats after 10 and 50 days of diabetes, and on groups of rats that, after
      initial hyperglycaemia for 50 days, were insulin treated for 2 h or for 5, 15 or
      38 days. A group of hyperglycaemic diabetic animals were fasted for 18 h. Another
      group of rats had acute hyperglycaemia induced by intravenous glucose injection.
      After 10 and 50 days of diabetes, kidney weight was increased by 55 and 93%.
      Glomerular volume, tubule length, and tubular and interstitial volume increased
      in diabetic animals compared with controls. After 4 h insulin treatment, the
      kidney weight was 20% decreased; after 5 days it was 31% decreased. After 38 days
      the kidney weight was still 26% greater than in controls. In diabetic animals, 18
      h fasting induced a 30% decrease in kidney weight. In normal animals, acute
      hyperglycaemia induced a 22% increase in kidney weight. Volume fractions of most
      kidney structures remained similar in all groups. However, the glomerular volume
      fraction was smaller during kidney enlargement, and the tubular volume fraction
      was larger after induced hyperglycaemia compared with controls. In conclusion,
      high blood glucose levels in diabetic and normal animals are associated with
      increased kidney weight. In hyperglycaemic diabetic animals, normalization of
      blood glucose after insulin treatment or fasting was followed by a decrease in
      kidney weight.

PMID- 9243100
TI  - Altered immunoreactivity of islet amyloid polypeptide (IAPP) may reflect major
      modifications of the IAPP molecule in amyloidogenesis.
AB  - We have developed a mouse monoclonal antibody against rat/mouse islet amyloid
      polypeptide (IAPP). The antibody recognises an epitope in the N-terminal part of
      the molecule, which is conserved between different species. The antibody
      immunohistochemically labelled beta cells in normal islets of most different
      mammalian species including man and in one avian species. Previous
      immunohistochemical studies of human pancreatic tissue from individuals with non
      insulin-dependent diabetes mellitus (NIDDM) have revealed a paradoxical and
      unexplained lack of IAPP immunoreactivity in beta cells close to amyloid in spite
      of the presence of IAPP mRNA. In contrast to these findings we show that the
      newly developed monoclonal IAPP antibody strongly labels such beta cells while
      islet amyloid deposits which are labelled by polyclonal antisera do not bind the
      monoclonal antibody. These findings with the polyclonal antisera and the
      monoclonal antibody indicate that IAPP undergoes one or several structural
      changes during the amyloidogenesis. Knowledge of these structural changes that
      may include abnormal folding or chemical modification of IAPP is probably
      important for the understanding of the amyloidogenesis and the pathogenesis of
      the islet lesion in NIDDM.

PMID- 9243102
TI  - Chronic leptin treatment does not prevent the development of obesity in
      transgenic mice with brown fat deficiency.
AB  - With the exception of ob/ob mice, circulating plasma leptin is elevated in all
      other obese rodents as well as in obese humans, suggesting that leptin resistance
      rather than leptin deficiency is a characteristic feature of obesity. The exact
      molecular mechanisms leading to leptin resistance and the applicability of
      exogenous leptin to overcome resistance to the anorectic effect of the hormone,
      are insufficiently characterized. The aim of this study was to investigate
      whether chronic leptin administration could prevent the development of obesity
      and its associated disorders in transgenic mice with toxigene mediated ablation
      of brown adipose tissue (BAT). Daily injections of leptin were started at the age
      of 6 weeks, when body weight, food intake and plasma leptin levels of transgenics
      were not different from control mice. Over the next 6 weeks, leptin treated
      transgenics showed the same excessive body weight gain as transgenic mice
      injected with saline. Leptin treatment was furthermore not able to prevent the
      development of hyperphagia, hyperglycaemia, hyperinsulinaemia and hyperlipidaemia
      in transgenic mice. In contrast, control mice injected with leptin had
      significantly lower body weight, food intake and plasma triglycerides than those
      treated with saline. In summary, leptin treatment was not able to prevent the
      development of obesity and its associated abnormalities in transgenic mice with
      BAT deficiency. This data suggests that intact BAT function is of critical
      importance for leptin's effect on food intake and energy expenditure, and that
      primary dysfunction of BAT is associated with leptin resistance, even when
      hyperleptinaemia is not yet present.

PMID- 9243103
TI  - Clustering of albumin excretion rate abnormalities in Caucasian patients with
      NIDDM. The Italian NIDDM Nephropathy Study Group.
AB  - Proteinuria and nephropathy have been found to cluster in families of non-insulin
      dependent diabetic (NIDDM) Pima Indian, and in Caucasian insulin-dependent
      diabetic (IDDM) patients. No information is at present available for Caucasian
      NIDDM patients. The aim of the present study was to determine whether micro
      macroalbuminuria (AER+) is associated with albumin excretion rate abnormalities
      in diabetic and non-diabetic siblings of probands with NIDDM and AER+. We
      identified 169 Caucasian families with one NIDDM proband (the patient with
      longest known NIDDM duration) (101 families with only NIDDM siblings, 33 families
      with both NIDDM and non-NIDDM siblings and 35 families with only non-NIDDM
      siblings). Of the probands 56 had AER+ [Prob-NIDDM-(AER+)], 78 had AER-[Prob
      NIDDM-(AER-)], 74 siblings of Prob-NIDDM-(AER+), and 113 siblings of Prob-NIDDM
      (AER-) also had NIDDM. Data on albuminuria and retinopathy from multiple sibling
      pairs when the size of the sibship was more than two was adjusted according to a
      weighting factor. The odds ratio for AER+, in siblings of Prob-NIDDM-(AER+)
      adjusted for age, hypertension, glycated haemoglobin A1c and other confounding
      variables was 3.94 (95% confidence intervals: 1.93-9.01) as compared to siblings
      of Prob-NIDDM-(AER-). The 74 siblings of Prob-NIDDM-(AER+) had higher prevalence
      of proliferative retinopathy than siblings of Prob-NIDDM-(AER-) (14 vs 2%; p <
      0.01). We also identified 66 non-diabetic siblings of 41 NIDDM probands with AER+
      and 36 non-diabetic siblings of 27 NIDDM probands with AER-. Albumin excretion
      was two times higher, although still within the normal range, in the non-diabetic
      siblings of Prob-NIDDM-(AER+) than in siblings of Prob-NIDDM-(AER-) [median =
      13.5 (range 0.5-148) vs 6.6 (range 1-17) micrograms/min (p < 0.05)]. In
      conclusion higher rates of albumin excretion aggregate in Caucasian families with
      NIDDM. Proliferative retinopathy is more frequently observed in families showing
      a clustering of AER+ and NIDDM. These findings suggest that familial factors play
      a role in the pathogenesis of renal and retinal complications in NIDDM.

PMID- 9243104
TI  - Prevalence of NIDDM and impaired glucose tolerance in a rural and an urban
      population in Cameroon.
AB  - The adoption of Western lifestyles is known to lead to increasing prevalence of
      non-insulin-dependent diabetes mellitus in Africa, yet epidemiological studies
      using standardised methods are rare. The prevalence of diabetes and impaired
      glucose tolerance was determined in a rural and an urban community in Cameroon
      using the 75-g oral glucose tolerance test and the World Health Organization
      diagnostic criteria in 719 rural (292 men, 427 women) and 1048 urban (458 men,
      590 women) subjects aged 24-74 years. The response rate was 95 and 91% for the
      rural and urban population, respectively. The age-standardized prevalence of
      diabetes in the rural and urban population was respectively 0.9% (95% confidence
      interval (0.2-2.7)) and 0.8% (0.2-1.8) for men and 0.5% (0.1-1.6) and 1.6% (0.7
      3.1) for women, and that of impaired glucose tolerance was 5.8% (3.3-9.4) and
      1.8% (0.9-3.2) for men, and for women, 2.2% (1.0-4.0) and 2.0% (0.6-4.5).
      Although for both men and women the body mass index was higher at all ages in the
      urban than in the rural area, the 2-h plasma glucose, even after adjustment for
      age and body mass index, was significantly higher in the rural than in the urban
      area (p < 0.005, p < 0.002 for men and women, respectively). There was a female
      excess of diabetes in the urban area and an equal sex distribution in the rural
      area. In the rural area 67% (4 of 6) of diabetic subjects were unknown before the
      survey, compared with 57% (8 of 14) in the urban area. These data indicate a low
      prevalence of diabetes in Cameroon; however, the prevalence of impaired glucose
      tolerance suggests an early stage of a diabetes epidemic.

PMID- 9243105
TI  - Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in
      relation to conversion to NIDDM: the Mexico City Diabetes Study.
AB  - Although insulin resistance and decreased insulin secretion are characteristic of
      established non-insulin-dependent diabetes mellitus (NIDDM), which of these
      metabolic abnormalities is the primary determinant of NIDDM is still
      controversial. A disproportionate increase in the proinsulin to insulin ratio has
      been proposed as a marker of compromised insulin secretion. We examined the
      association of fasting immunoreactive insulin (which cross-reacts with
      proinsulin), specific insulin (which does not cross-react with proinsulin), total
      immunoreactive proinsulin (or insulin precursors), and the fasting
      proinsulin/specific insulin ratio to the risk of developing NIDDM in the 3.25
      year follow-up of the Mexico City Diabetes Study. These measurements were made in
      85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85
      age and gender matched subjects who remained non-diabetic at follow-up (control
      subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin
      ratio were significantly higher in prediabetic than in control subjects. However,
      the relation between specific insulin and the development of NIDDM was weaker
      than for proinsulin or immunoreactive insulin. After further adjustment for
      obesity, body fat distribution and glucose tolerance status, proinsulin and the
      proinsulin/specific insulin ratio, but not specific or immunoreactive insulin,
      predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted
      conversion to NIDDM both in subjects with normal and those with impaired glucose
      tolerance at baseline. We conclude that in prediabetic subjects increased
      proinsulin, a marker of islet cell distress or compromised insulin secretion, is
      associated with rapid conversion (within 3.25 years) to NIDDM even in obese
      populations.

PMID- 9243106
TI  - No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in
      subcutaneous adipose tissue.
AB  - A Trp64Arg variant in the human beta 3-adrenoceptor is associated with earlier
      onset of non-insulin-dependent diabetes mellitus and obesity in several
      populations. The present study investigated in vivo lipolysis in individuals
      homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of
      the beta 3-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp)
      allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6
      females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m2, 43 +/- 11% body fat [mean
      +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1
      kg/m2, 39 +/- 9% body fat). After an overnight fast, a microdialysis probe was
      inserted in the subcutaneous adipose tissue and perfused with Ringer's solution.
      Dialysate was collected in 10-min fractions during a 30-min baseline and during
      40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the
      perfusate (1 mumol/l). Changes in rate of lipolysis were assessed as changes in
      dialysate glycerol concentration. The relative changes in dialysate glycerol
      concentrations in response to isoproterenol, expressed as percent over baseline,
      were similar in the two groups (i.e. 63 +/- 30 and 74 +/- 28% in the Arg and Trp
      subjects, respectively). The results were also similar in the two groups after
      adjustment for sex and percentage of body fat. No differential effect of
      isoproterenol on blood flow was demonstrated between the two groups (assessed by
      the ethanol dilution technique). These results are consistent with in vitro
      studies showing no functional effect of the beta 3-adrenoceptor variant, and/or
      indicate that the beta 3-adrenoceptor is not very important for subcutaneous
      adipose tissue lipolysis.

PMID- 9243107
TI  - Short-term oestrogen replacement therapy improves insulin resistance, lipids and
      fibrinolysis in postmenopausal women with NIDDM.
AB  - Oestrogen replacement therapy is associated with a decreased risk of
      cardiovascular disease in postmenopausal women. Patients with non-insulin
      dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk.
      However, oestrogen replacement therapy is only reluctantly prescribed for
      patients with NIDDM. In a double blind randomized placebo controlled trial we
      assessed the effect of oral 17 beta-estradiol during 6 weeks in 40 postmenopausal
      women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity,
      suppressibility of hepatic glucose production, lipoprotein profile and parameters
      of fibrinolysis were determined. The oestrogen treated group demonstrated a
      significant decrease of HbA1c and in the normotriglyceridaemic group a
      significantly increased suppression of hepatic glucose production by insulin.
      Whole body glucose uptake and concentrations of non-esterified fatty acids did
      not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL
      cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased.
      The plasma triglyceride level remained similar in both groups. Both the
      concentration of plasminogen activator inhibitor-1 antigen and its active
      subfraction decreased. Tissue type plasminogen activator activity increased
      significantly only in the normotriglyceridaemic group. Oestrogen replacement
      therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein
      profile and fibrinolysis in postmenopausal women with NIDDM. For a definite
      answer as to whether oestrogens can be more liberally used in NIDDM patients,
      long term studies including the effect of progestogens are necessary.

PMID- 9243108
TI  - Relationship between insulin-mediated glucose disposal and regulation of plasma
      and adipose tissue lipoprotein lipase.
AB  - The relationship between insulin-mediated glucose disposal and fasting insulin
      and triglyceride (TG) concentrations, plasma post-heparin lipoprotein lipase (PH
      LPL) activity and mass, and adipose tissue LPL activity, mass, and mRNA content
      was defined in 19 non-diabetic men. Insulin-mediated glucose uptake [as assessed
      by determining the steady-state plasma glucose (SSPG) concentration during a
      continuous infusion of somatostatin, insulin, and glucose] was significantly
      correlated with fasting TG concentration (r = 0.54, p < 0.02), plasma PH-LPL
      activity (r = -0.52, p < 0.03) and mass (r = -0.49, p < 0.03), and adipose tissue
      LPL mRNA content (r = -0.68, p < 0.001). Comparable relationships were also seen
      when fasting insulin concentration was substituted for SSPG. Although adipose
      tissue LPL and mass correlated with each other (r = 0.76, p < 0.001) in a fasting
      state, they were not related to any other variable measured. Using in vivo and
      molecular biology techniques, these data demonstrate that the more insulin
      resistant an individual, the lower the level of plasma PH-LPL activity and mass,
      and the higher the plasma TG concentration. Since lower concentrations of adipose
      tissue mRNA were also directly correlated with plasma PH-LPL mass (r = 0.57, p <
      0.01), and inversely with plasma TG concentration (r = -0.68, p < 0.001) as well
      as SSPG (r = -0.68, p < 0.001), it can be postulated that the relationship
      between insulin resistance and LPL activity and plasma TG concentration is
      associated with the inability of insulin to stimulate the transcription or to
      increase the intracellular mRNA stability of adipose tissue LPL in insulin
      resistant individuals.

PMID- 9243109
TI  - A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK
      pedigree with maturity-onset diabetes of the young.
AB  - Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non
      insulin dependent diabetes mellitus (NIDDM) characterised bylan early age of
      onset (< 25 years) and an autosomal dominant mode of inheritance. MODY is
      genetically heterogeneous with three different genes identified to date;
      hepatocyte nuclear factor 4 alpha (HNF-4 alpha) [MODY1], glucokinase [MODY2] and
      hepatocyte nuclear factor 1 alpha (HNF-1 alpha) [MODY3]. A nonsense mutation in
      the HNF-4 alpha gene has recently been shown to cause MODY in a single large
      North American pedigree (RW). We screened a large UK Caucasian MODY family which
      showed weak evidence of linkage to the MODY1 locus on chromosome 20q (lod score
      for ADA 0.68 at theta = 0) for mutations in the coding region of the HNF-4 alpha
      gene by direct sequencing. A missense mutation resulting in the substitution of
      glutamine for glutamic acid was identified in exon 7 (E276Q). The mutation was
      present in all of the diabetic members of the pedigree plus two unaffected
      subjects and was not detected in 75 normal control subjects or 95 UK Caucasian
      subjects with late-onset NIDDM. This is the first missense mutation to be
      described in the HNF-4 alpha gene.

PMID- 9243110
TI  - Protein kinase C isoforms beta 1 and beta 2 inhibit the tyrosine kinase activity
      of the insulin receptor.
AB  - Downregulation of insulin receptor tyrosine kinase (IRK) activity yields to
      impaired insulin signalling and contributes to the pathogenesis of cellular
      insulin resistance. Activation of protein kinase C (PKC) by different agents is
      associated with an inhibition of IRK activity in various cell types. There is
      evidence that this effect on IRK activity might be mediated through
      phosphorylation of specific serine residues of the insulin receptor beta-subunit.
      Neither the domains of the IRK where inhibiting serine phosphorylation occurs nor
      the PKC isoform responsible for IRK inhibition have been identified. PKC consists
      of a family of at least 12 isoforms. The aim of the present study was to
      determine which PKC isoform might be capable of IRK inhibition. The human insulin
      receptor and the PKC isoforms alpha, beta 1, beta 2, gamma, delta, epsilon, eta,
      theta and zeta were overexpressed in human embryo kidney fibroblasts (HEK 293
      cells) in order to answer this question. PKCs were activated by preincubation
      with the phorbolester (TPA) (10(-7) mol/l) following insulin stimulation of the
      cells. When the IRK was coexpressed with the PKC isoforms beta 1 and beta 2, a 50
      +/- 15.7 and 45 +/- 10.1% inhibition of tyrosine autophosphorylation of IRK was
      observed while coexpression with the other isoforms did not significantly modify
      IRK autophosphorylation. The data suggest that the PKC isoforms beta 1 and beta 2
      might be candidates for insulin receptor inhibition.

PMID- 9243111
TI  - Aspirin therapy in diabetes mellitus.

PMID- 9243112
TI  - NOD mice as a model for inherited deafness.

PMID- 9243113
TI  - Macromolecular protein complex in human plasma may explain altered fibrin gel
      structure in IDDM patients.

PMID- 9243114
TI  - Gastritis and Helicobacter pylori: forty years of antibiotic therapy.
AB  - Helicobacter pylori has now been propelled into the forefront of
      gastroenterology, particularly the treatment of gastroduodenal ulcer, whereas its
      role in gastritis is still widely ignored, although this disease sparked much of
      the original observations. Forty years ago, it was shown for the first time that
      antibiotics can eliminate gastric ammonia production in man which suggested that
      this was due to eradication of bacterial urease activity. It was also found that
      the gastric juice ammonia concentration correlates with hypo- or anacidity in
      uremics and with mucosal inflammation in subjects with gastritis. In patients
      with nonalcoholic and alcoholic gastritis, the histology as well as the symptoms
      of gastritis were strikingly improved by antibiotic treatment. Beneficial effects
      of eradication of gastric urease activity and the resulting decreased ammonia
      production were also shown in patients with hepatic encephalopathy. Broader
      studies and clinical applications of these earlier findings are now warranted.

PMID- 9243115
TI  - Antral mucosal Helicobacter pylori infection density as a risk factor of duodenal
      ulcer.
AB  - OBJECTIVE: Duodenal ulcer is regarded as the end result of alterations in which
      Helicobacter pylori (HP) plays a major role as a pathogenetic agent. The aim of
      this prospective study was to evaluate duodenal ulcer risk factors such as
      alcohol intake, smoking, use of non-steroidal anti-inflammatory drugs, age and
      sex in relation to HP colonization density. PATIENTS AND METHODS: 495 patients
      consecutively examined by diagnostic upper digestive endoscopy were assessed;
      none of them had had previous upper digestive endoscopy or peptic ulcer, recent
      anticulcer-antibiotic treatment, upper gastrointestinal surgery, or cancer. The
      HP colonization on antral bioptic specimens was graded semi-quantitatively as
      follows: HP--- (absence of HP); HP+--(focal presence of small amounts of HP);
      HP++- (intermediate situation between HP+-- and HP+++), and HP+++ (diffuse
      presence of large amounts of HP). RESULTS: Logistic regression analysis
      identified only male sex (odds ratio 1.88, p < 0.02), smoking more than 10
      cigarettes/day (odds ratio 2.53, p < 0.01), and HP grade (HP +-- odds ratio 0.79,
      p = NS; HP++- odds ratio 2.42, p < 0.02; HP+++ odds ratio 3.66, p < 0.001) as
      independent risk factors of duodenal ulcer. CONCLUSION: The duodenal ulcer risk
      was found to correlate with HP density, male sex, and smoking, but not with non
      steroidal anti-inflammatory drug use.

PMID- 9243116
TI  - Malignant gastrointestinal lymphomas in patients with AIDS.
AB  - HIV-associated malignant lymphomas are a common complication in late HIV
      infection, and there is a high percentage of gastrointestinal tract involvement.
      Non-Hodgkin's lymphoma was found in 108 of 2,750 HIV-positive patients (3.9%) in
      our institution, whereas gastrointestinal manifestation was diagnosed in 48 of
      108 patients (44.4%). 44 of these cases were found during endoscopy of the upper
      and lower gastrointestinal tract (or by laparotomy or laparoscopy in 4 cases).
      Endoscopy is a reliable procedure for the diagnosis of lymphoma. Unusual
      manifestations such as oral, esophageal or perianal lesions and multifocal
      disease were common findings. Life-threatening complications such as
      gastrointestinal bleeding, perforation, and obstruction occurred in 37.5%. High
      grade B-cell lymphomas were found in all cases including mainly lymphoblastic,
      immunoblastic, centroblastic and Burkitt subtypes. 52% of the patients had
      disseminated lymphoma with Ann Arbor stage III or IV. Standard chemotherapy with
      cyclophosphamide, adriamycin, vincristine and prednisone was started  in 25
      patients and resulted in a mean survival time of 4.8 months. The prognosis of
      AIDS patients presenting with malignant gastrointestinal lymphoma depends mainly
      on the presence or absence of previous AIDS-defining diseases, not CD4 cells,
      lymphoma-associated gastrointestinal complications or the histopathologic
      lymphoma type at the time of diagnosis.

PMID- 9243117
TI  - Production and activation of hepatocyte growth factor during the healing of rat
      gastric ulcers.
AB  - The hepatocyte growth factor has been reported to be a potent mitogen of various
      epithelial cells, including gastric mucosal cells. Therefore, production and
      activation of hepatocyte growth factor in the gastric wall were investigated to
      speculate on the possible role of this factor in the healing of gastric ulcer in
      rats. Indomethacin-induced gastric mucosal lesions and acetic acid induced ulcers
      were employed as models of acute gastric lesions and chronic ulcer, respectively.
      Immunoblot and Northern blot analyses indicate that experimentally induced
      gastric mucosal lesions stimulate not only the production of hepatocyte growth
      factor, but also the conversion to its active form. This conversion was
      accompanied by increased gene expression of hepatocyte growth factor activator in
      the stomach. In rats with acute mucosal lesions, hepatocyte growth factor
      activator mRNA was most abundant 6 h after induction of mucosal lesions. On the
      other hand, hepatocyte growth factor and hepatocyte growth factor activator mRNA
      levels were elevated until 15 days after the induction of chronic ulcers. In
      summary, it has been clarified that not only production, but also activation of
      hepatocyte growth factor is stimulated during gastric ulcer healing.

PMID- 9243118
TI  - Involvement of capsaicin-sensitive sensory nerves in gastric adaptive relaxation
      in isolated guinea-pig stomachs.
AB  - We investigated the role of capsaicin-sensitive sensory nerves (CPSNs), nitric
      oxide (NO), calcitonin gene-related peptide (CGRP) and vasoactive intestinal
      peptide (VIP) in gastric adaptive and receptive relaxation in isolated guineapig
      stomachs. Changes in intragastric volume and pressure were recorded
      simultaneously in isolated stomachs in baths containing atropine and
      guanethidine. Adaptive relaxation was induced by luminal distention, and
      receptive relaxation was induced by electrical vagal stimulation. We found that
      desensitization to capsaicin inhibited adaptive relaxation, but not vagally
      induced relaxation. Extraluminal capsaicin induced gastric relaxation. Adaptive
      relaxation and capsaicin-induced relaxation were reduced by both tetrodotoxin and
      NG-nitro-L-arginine (LNNA), but not by hexamethonium. The effect of LNNA was
      partially reversed by co-incubation with L-arginine. Neither CGRP(8-37) nor
      VIP(10-28) inhibited all responses of adaptive relaxation, vagally induced and
      capsaicin-induced relaxation. These findings suggest that activation of CPSNs may
      be involved in adaptive relaxation, and that NO, but not CGRP or VIP, may be
      involved in the mechanisms of adaptive relaxation and receptive relaxation.

PMID- 9243119
TI  - Small bowel lengthening by mechanical distraction.
AB  - To evaluate whether the small bowel can be distracted by mechanical stress in
      analogy to limb lengthening by osteodistraction, a gut-lengthening apparatus was
      designed. This distractor was placed at the antimesenterical side of a defined
      jejunum segment in rabbits. Distraction was performed by 1 mm lengthening of the
      distractor once daily using extracorporal screws. An effective gut lengthening
      was achieved of 9.9 +/- 0.5 mm (approximately 100%) within 3 weeks. Treated
      animals gained weight and remained in good general condition. Fasting plasma
      levels of cholecystokinin, neurotensin, glucagon-like peptide-1, gastric
      inhibitory polypeptide, and insulin remained unaffected. Postoperative factor
      XIII levels were significantly diminished and gastrin was elevated during gut
      distraction. DNA and protein concentrations in the mucosa of the distracted gut
      segments corresponded to controls. Mucosal lactase and saccharase activities were
      reduced. In the distracted bowel segments total tunica muscularis thickness was
      more than doubled due to muscle cell hypertrophy. In distracted segments villous
      width was increased. Detection of proliferating mucosal crypt cells utilizing
      BrdUrd labeling revealed no effects. In conclusion, small gut lengthening by
      mechanical distraction is possible without major changes in gut morphology. This
      technique may hint a novel experimental approach for the treatment of short bowel
      syndrome.

PMID- 9243120
TI  - Prostaglandin E2 modulates serotonin- and gastrin/CCK-immunoreactive cells in the
      duodenal mucosa of the rat.
AB  - Groups of Sprague-Dawley rats were given placebo or prostaglandin E2 (PGE2) at 25
      or 5,000 micrograms/kg or 15,R,15-methyl-PGE2 (MePGE2) at 5 or 50 micrograms/kg,
      twice daily, orally, for 1 month. Histological sections from the proximal
      duodenum were processed for immunohistochemistry and the volume density of
      immunoreactive endocrine cells was determined using point-counting grids. The
      surface density of the villous lining was estimated by using a cycloid test
      system. Thereafter, the total volumes of endocrine cells and the total surface
      area of the villous lining were calculated after estimating the mucosal volume.
      The volume density of serotonin-immunoreactive cells was increased in the
      duodenum of rats given 25 or 5,000 micrograms/kg PGE2 (p < 0.05). The total
      volume of these cells increased in the animals given 25 micrograms/kg PGE2 (p <
      0.05). The total volume of gastrin/CCK-immunoreactive cells was higher in rats
      given 25 micrograms/kg PGE2 or 50 micrograms/kg MePGE2 than in controls (p <
      0.05). The volume density of somatostatin-immunoreactive cells increased in rats
      given 5 micrograms/kg MePGE2, but the total volumes were not different between
      the groups. The area of somatostatin-immunoreactive cell profiles was enlarged in
      the animals given 5,000 micrograms/kg PGE2 (p < 0.05). The mucosal volume was
      enlarged by prostaglandins. The epithelial thickness increased in rats given the
      highest doses of PGE2 (p < 0.05). The concentration of motilin-like
      immunoreactivity increased in the duodenum of rats given 5 micrograms/kg MePGE2
      (p < 0.05). We conclude that oral administration of PGE2 for 1 month increased
      the total volumes of serotonin- and gastrin-CCK-immunoreactive cells and the
      tissue concentration of motilin-like immunoreactivity, which indicates that
      prostaglandins modulate endocrine cells in a stable steady-state condition.

PMID- 9243121
TI  - Importance of intracellular S-adenosylmethionine decarboxylase activity for the
      regulation of camostate-induced pancreatic polyamine metabolism and growth: in
      vivo effect of two novel S-adenosylmethionine decarboxylase inhibitors.
AB  - The present study was designed to investigate the inhibitory potency of the two
      novel S-adenosylmethionine decarboxylase (SAM-DC) inhibitors MDL 73811 and CGP
      48664 on the camostate-induced pancreatic polyamine metabolism and especially
      intracellular spermidine accumulation as well as pancreatic growth in vivo. Male
      Wistar rats (180 g) were either treated with (1) the synthetic trypsin inhibitor
      camostate (200 mg/kg b.w. orally twice daily), (2) camostate+MDL 73811 (100 mg/kg
      b.w. i.p. twice daily), (3) camostate+CGP 48664 (5 mg/kg b.w. i.p. once daily) or
      (4) saline as controls. Animals (5-9 per group) were sacrificed after 1, 2 and 5
      days of treatment. MDL 73811 caused a long-lasting (> 95%; p < 0.005) inhibition
      of SAM-DC followed by a significant (p < 0.005) increase in ornithine
      decarboxylase and putrescine, while spermine was decreased (p < 0.005). In
      contrast to MDL 73811, CGP 48664 had little effect in vivo. Despite potent
      inhibition of SAM-DC camostate-stimulated intracellular spermidine accumulation
      was not prevented by the simultaneous administration of MDL 73811. Consequently
      organ growth was not affected either. Since de novo synthesis of spermidine was
      effectively inhibited by MDL 73811, counterregulatory mechanisms (i.e.
      interconversion pathway, extracellular uptake) had to step in to maintain the
      intracellular balance of spermidine. The present data support the general concept
      of the importance of intracellular spermidine accumulation for the maintenance of
      pancreatic growth in vivo.

PMID- 9243122
TI  - Ulcerative colitis in Oman. A prospective study of the incidence and disease
      pattern from 1987 to 1994.
AB  - OBJECTIVE: Inflammatory bowel disease has been reported to have varying
      frequencies in different parts of the world, and there seem to be significant
      differences in the disease pattern and clinical course in cases of ulcerative
      colitis (UC). The aim of the present study was to assess the incidence and
      disease pattern of UC in Oman. METHOD: A prospective study, over a period of 8
      years (1987-1994), was performed to study 108 patients found to have UC. RESULTS:
      The annual incidence of UC was 1.35/100,000. The disease was mainly seen in the
      middle and upper middle class group, and the majority were nonsmokers or
      exsmokers. There was no significant difference in the incidence of the disease
      between nationalities or sexes. Total colitis was seen in 18%, and a significant
      number had disease extending up to the splenic flexure. Proctitis was seen in 8%.
      Although, the extent of the disease was similar to reports from the West, these
      patients had fewer hospital admissions, blood transfusions and none of them
      suffered local complications such as toxic dilatation, perforation or severe
      bleeding. Sclerosing cholangitis occurred in 2 patients. Patients were followed
      up for a maximum period of up to 7 years after diagnosis and none developed
      dysplasia or cancer. Three patients had surgery mainly for failure of medical
      treatment. CONCLUSIONS: From this report it seems that UC occurs in Oman at a
      lower frequency compared to the West. Although, the extent of the disease was
      similar to Europeans, these patients had less severe disease with fewer
      complications.

PMID- 9243123
TI  - Role of cytokines in experimental colitis: relation to intestinal permeability.
AB  - There is now clear evidence supporting the role of cytokines in the clinical and
      immunopathological manifestations of human inflammotory bowel disease. The
      purpose of the present study was to determine the possible role of a cytokine
      network in a rat model of trinitrobenzene sulfonic acid-induced colitis and to
      examine its relation to intestinal permeability. After a rapid increase in the
      intestinal permeability of Evans blue in the colon, tumor necrosis factor-alpha
      increased transiently, and interleukin-1 and interleukin-6 followed thereafter.
      The majority of tumor necrosis factor-alpha- and interleukin-1-producing cells
      observed by immunofluorescent staining was revealed to be macrophages. Repeated
      injections of interleukin-1 receptor antagonist led to a modest decrease in
      myeloperoxidase activity and colon weight. These findings suggest that enhanced
      pro-inflammatory cytokine production from intestinal macrophages accompanied by
      increased intestinal permeability may contribute to intestinal and systemic
      features of trinitrobenzene sulfonic acid-induced colitis. Pharmacologic blockade
      of pro-inflammatory cytokines may help reduce intestinal inflammation.

PMID- 9243124
TI  - Validation of the Dutch translation of the Inflammatory Bowel Disease
      Questionnaire (IBDQ): a health-related quality of life questionnaire in
      inflammatory bowel disease.
AB  - Health-related quality of life assessment can benefit several groups involved
      with health care. The aim of our study was to assess construct validity,
      reliability, discriminant ability and sensitivity to change of the Dutch
      translation of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease
      specific quality-of-life questionnaire. A group of 120 IBD patients completed the
      IBDQ and two Visual Analogue Scales concerning general well-being and bowel
      function twice. Fifty-two patients also completed the Short-Form 36 twice.
      Disease activity was assessed once. Correlations between the IBDQ scores and the
      global assessments were reasonably high and the IBDQ was shown to be
      discriminative. High intraclass correlation coefficients between both
      measurements of the IBDQ were observed in patients who reported no change in
      bowel complaints. In contrast, significant differences were found between both
      moments in patients who reported change. The Dutch IBDQ proved to be valid,
      discriminative and reliable.

PMID- 9243125
TI  - Meglumine gadoterate: a new safe radiocontrast medium for endoscopic retrograde
      cholangiopancreatography?
AB  - The radiocontrast substance meglumine gadoterate (MG) is used in magnetic
      resonance imaging. It is characterized by its low rate of adverse drug reactions.
      In an open study we tested whether MG is useful in endoscopic retrograde
      cholangiopancreatography. The patients received in sequence MG and ioxotalamate.
      MG, in contrast to ioxotalamate, failed to visualize the proximal pancreatic and
      peripheral intrahepatic ducts. Thus, MG is not useful in routine endoscopic
      retrograde cholangiopancreatography. However, in patients with a history of
      severe allergic reactions to conventional contrast media, MG may be recommended
      when pathological findings of the extrahepatic bile duct or the area of the
      pancreatic head are suspected.

PMID- 9243126
TI  - Prevalence and incidence of cholecystolithiasis in cirrhosis and relation to the
      etiology of liver disease.
AB  - To assess prevalence and incidence of cholecystolithiasis in cirrhosis, 356
      consecutive cirrhotics and 247 consecutive cases of chronic hepatitis without
      cirrhosis were studied by ultrasonography. Cholecystolithiasis was significantly
      more frequent in cirrhotics than in patients with chronic hepatitis (p < 0.001)
      after stratification for age and for alcohol abuse, and its prevalence in the
      former was affected by Child's class (p < 0.001) and duration (p < 0.001) of
      cirrhosis and was higher in HBsAg-negative as compared with HBsAg-positive cases
      (36.2 vs. 11.9%) and in patients with previous alcohol abuse (41.5 vs. 28.3%),
      while no difference was noted in relation to sex. By multivariate analysis,
      duration and Child's class of cirrhosis and HBsAg-negative status were
      statistically associated with cholecystolithiasis. One hundred and eighty-two of
      the 356 cirrhotic patients without gallstones at inclusion were followed
      prospectively, and 21 (11.5%) of them developed cholecystolithiasis, and duration
      of cirrhosis and past alcohol abuse were found to be independent risk factors for
      gallstone development by multivariate analysis. Cirrhosis is a significant risk
      factor for cholecystolithiasis, except for HBsAg-positive patients who have
      prevalence and incidence similar to noncirrhotics. Severity and duration of
      cirrhosis and previous alcohol abuse are associated with an increased risk of
      gallstone formation.

PMID- 9243128
TI  - 5-Aminosalicylic acid-associated renal tubular acidosis with decreased renal
      function in Crohn's disease.
AB  - The use of 5-aminosalicylic acid (5-ASA, mesalazine) in Crohn's disease is
      usually well tolerated. Nevertheless, the occasional occurrence of nephrotoxic
      side effects has been described in several case reports. We present the case of a
      34-year-old female in whom chronic use of 5-ASA may have caused renal damage
      which manifested with tubular acidosis, severe weight loss, shortness of breath
      and fatigue. For 17 years the patient has suffered from Crohn's disease. She
      received sulfasalazine (3 g/day) for 12 years and was treated with resin-coated
      mesalazine (3 g/day) for the last 72 months. Onset of weight loss of 10 kg over a
      6-month period, accompanied by progressive shortness of breath and fatigue, lead
      to a diagnosis of metabolic acidosis and renal bicarbonate loss due to damage to
      the tubular epithelium. Kidney biopsy demonstrated acute interstitial nephritis
      which may be related to 5-ASA.

PMID- 9243127
TI  - Helicobacter pylori culture supernatant inhibits binding and proliferative
      response of human gastric cells to epidermal growth factor: implications for
      H.pylori interference with ulcer healing?
AB  - Helicobacter pylori (H. pylori) infection of gastric mucosa is strongly
      associated with gastritis and peptic ulcer disease. However, the mechanisms of
      the ulcerogenic action of H. pylori and/or the interference of H. pylori with
      ulcer healing are unknown. Through binding to its receptor, epidermal growth
      factor (EGF) accelerates cells migration and triggers epithelial cell
      proliferation which are both important for the healing of gastroduodenal ulcers.
      H. pylori seems to interfere with ulcer healing, but the cellular and molecular
      targets and mechanisms of these actions have not been elucidated. In the present
      study, we tested the effect of H. pylori culture supernatant (dialyzed to remove
      molecules smaller than 10 kD) on EGF binding to its receptor and on the
      proliferative response of human gastric Kato III cells to EGF. H. pylori culture
      supernatant significantly reduced specific binding of EGF to its receptor and
      reduced EGF-stimulated gastric cell proliferation. Since ulcer healing requires
      epithelial cell proliferation and cell migration (re-epithelialization), which
      are both triggered by EGF binding to its receptor, the alteration in these
      mechanisms by H. pylori product may be the basis of H. pylori-induced
      interference with ulcer healing.

PMID- 9243129
TI  - Anticoagulation and left ventricular dysfunction: friend or foe?

PMID- 9243130
TI  - Angioplasty registries: wide open for audit?

PMID- 9243131
TI  - Prosthetic aortic valves.

PMID- 9243132
TI  - Thrombolysis in acute pulmonary embolism: to whom, how much and how?

PMID- 9243133
TI  - Factors associated with in-hospital death from myocardial infarction.

PMID- 9243134
TI  - Non-cardiac origin of out-of-hospital cardiac arrests: do we underestimate their
      frequency and prognosis?

PMID- 9243135
TI  - Structural arteriolar changes in diabetes mellitus.

PMID- 9243136
TI  - Postviral autoimmune heart disease--fact or fiction?

PMID- 9243137
TI  - Reconstruction and quantification with three-dimensional intracoronary
      ultrasound. An update on techniques, challenges, and future directions.

PMID- 9243138
TI  - The 1996 Gruntzig Lecture. Stents: a mechanical solution for a biological
      problem?

PMID- 9243139
TI  - Changing characteristics and in-hospital outcome in patients admitted with acute
      myocardial infarction. Observations from 1982 to 1994.
AB  - BACKGROUND: During the past decade, various new treatments have become available
      for patients with acute myocardial infarction. The effects of these treatment
      modalities have been studied extensively in selected patient groups. These
      studies indicate that early diagnosis, risk stratification and prompt initiation
      of treatment are of crucial importance for optimal benefit. However, it is not
      known whether prognosis changed in all patients admitted with an acute myocardial
      infarction. Also, the characteristics of the infarct population may have changed
      over time because of new medication regimens, invasive interventions and
      awareness of the importance of risk factors. METHODS: We studied all patients
      admitted with acute myocardial infarction in 1982, 1988 and 1994. Information on
      baseline characteristics, clinical variables and all interventions was collected.
      FINDINGS: In those 3 years 223, 227 and 235 patients were admitted because of an
      acute myocardial infarction. Patients admitted in 1994 were older, more often
      female and less often had a previous cardiac history. More patients admitted in
      that year had previous balloon angioplasty and coronary bypass grafting. Smoking
      habits decreased during the past decade. In-hospital mortality was 38 (17%) in
      1982, 23 (10%) in 1988 and 22 (9%) in 1994 (P < 0.05). Variables related to high
      risk for in-hospital death in 1982 were higher age, low systolic blood pressure,
      atrial fibrillation, absence of accelerated idioventricular rhythm, sustained
      ventricular tachycardia and signs of left ventricular dysfunction; in 1988 the
      occurrence of non-sustained ventricular tachycardia, Killip class more than I,
      the absence of thrombolytic therapy, percutaneous transluminal coronary
      angioplasty or coronary artery bypass grafting were independently related to in
      hospital death. In 1994, high risk variables for in-hospital death were dyspnoea
      on admission, sustained ventricular tachycardia, female gender, higher creatinine
      on admission, and a previous cardiac history. INTERPRETATION: In-hospital
      mortality for unselected patients admitted with an acute myocardial infarction
      decreased between 1982 and 1988 and remained the same between 1988 and 1994, in
      spite of further ageing of the population. In the study period there has been a
      change in baseline characteristics and high risk variables for in-hospital death
      after myocardial infarction.

PMID- 9243140
TI  - Evolution of coronary atherosclerosis in patients with mild coronary artery
      disease studied by serial quantitative coronary angiography at 2 and 4 years
      follow-up. The Multicenter Anti-Atheroma Study (MAAS) Investigators.
AB  - AIMS: Angiographic studies on the natural course of both focal and diffuse
      coronary atherosclerosis have not been performed before, but can both be assessed
      by quantitative coronary angiography. The objective of this study was to describe
      the natural course of focal and diffuse coronary atherosclerosis over time.
      METHODS AND RESULTS: In 129 patients with mild coronary artery disease, but not
      on lipid-lowering medication, three coronary angiograms were made each 2 years
      apart. Nine hundred and sixty five angiographically diseased and non-diseased
      segments were analysed by quantitative coronary angiography. Mean lumen diameter
      and minimal lumen diameter were used as measures of diffuse and focal coronary
      atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02
      and 0.03 mm per year. The rate of progression was similar in the angiographically
      non-diseased, as in the mildly and moderately diseased segments. Progression of
      diffuse coronary atherosclerosis was largest in severely stenosed lesions
      (percentage diameter stenosis > or = 50%) and in the right coronary artery with a
      loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease
      was most prominent in new and mild lesions and the right coronary artery, with a
      decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups,
      progression occurred gradually over time. On a per segment level, progression and
      the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and
      disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level,
      36% were progressors, 12% had a mixed response, 36% were stable, and 16% were
      regressors. CONCLUSION: Diffuse and focal coronary atherosclerosis progressed at
      the same rate in the first and second 2 years in stenosed and non-stenosed
      segments. The rate of coronary atherosclerosis progression was small, but was
      higher for focal than for diffuse disease. A minority of lesions progressed and
      spontaneous regression was rare.

PMID- 9243141
TI  - Impaired compensatory coronary artery enlargement in atherosclerosis contributes
      to the development of coronary artery stenosis in diabetic patients. An in vivo
      intravascular ultrasound study.
AB  - AIMS: Coronary arteries affected by atherosclerosis undergo focal compensatory
      enlargement, which can be detected by intracoronary ultrasound but not by
      angiography. Diabetic patients when compared with non-diabetics have a more
      accelerated progression of coronary artery disease and a more diffuse narrowing
      of the coronary arteries. Intracoronary ultrasound can clarify if this is due to
      less compensatory coronary artery enlargement as a response to atherosclerosis.
      METHODS AND RESULTS: Ten non-diabetic and 15 diabetic patients with coronary
      artery disease, with angiographically determined one- or two-vessel disease,
      underwent intracoronary ultrasound examination of the non-stenotic coronary
      artery. Forty-five sites with luminal stenosis, detected by intracoronary
      ultrasound, were analysed (15 in non-diabetics, 30 in diabetics). Vessel and
      lumen area, atherosclerotic plaque area and plaque composition were evaluated.
      Vessel area was also measured proximal and distal to the healthy segment. In the
      diabetic patients, there was less vessel area increase from the proximal healthy
      segment into the atherosclerotic segment than in the non-diabetic patients (99%
      separate-variance confidence intervals for differences between diabetics' and non
      diabetics' means = 0.29 mm2, 2.71 mm2). The proximal plaque free vessel area, the
      atherosclerotic plaque area and plaque composition were similar between the two
      groups. CONCLUSION: Diabetics with atherosclerosis have less compensatory
      coronary artery enlargement than non-diabetics. This may explain the diffuse and
      accelerated course of coronary artery disease in these patients.

PMID- 9243142
TI  - Lymphocyte responses to Chlamydia antigens in patients with coronary heart
      disease.
AB  - AIMS: To clarify the relationship of Chlamydia pneumoniae infection and coronary
      atherosclerosis we studied cell-mediated and humoral immune responses to
      Chlamydia in 93 patients with angiographically confirmed coronary heart disease
      and in 115 controls without angiographically demonstrable lesions. METHODS AND
      RESULTS: Cell-mediated responses were analysed by measuring lymphocyte
      proliferative reactivity to whole elementary body antigens of C. pneumoniae.
      Control antigens included C. trachomatis and purified protein derivative of
      tuberculin. Chlamydia-specific antibodies were measured using
      microimmunofluorescence assay. Marked C. pneumoniae-specific immune reactivity,
      demonstrated by the high incidence of elevated IgG and IgA antibodies and strong
      lymphocyte proliferative response, was associated with coronary heart disease in
      male but not in female patients or controls. In male patients, the cell-mediated
      responses were strong to C. pneumoniae (median stimulation index 9,6) and to C.
      trachomatis (stimulation index 6,9). The females with coronary heart disease
      showed significantly stronger cell-mediated responses to C. pneumoniae
      (stimulation index 6,5) than to C. trachomatis (3,8; P < 0.001) and were
      comparable to the controls. CONCLUSION: Marked cell-mediated and humoral immunity
      to C. pneumoniae in males with coronary heart disease suggest that the immune
      mechanisms triggered by Chlamydia are a possible contributing factor in the
      disease pathogenesis of coronary atherosclerosis in males. The Chlamydia-specific
      cell-mediated responses seem to be predominantly induced by antigenic structures
      that are similar among different Chlamydia-species.

PMID- 9243143
TI  - An economic analysis of ischaemic heart disease in Switzerland.
AB  - AIMS: Direct and indirect costs of ischaemic heart disease were assessed in
      Switzerland, for the period 1988-1993, in order to evaluate the economic
      consequences of more intensive treatment of the disease and of the decreasing
      mortality from ischaemic heart disease in the working population. METHODS AND
      RESULTS: A societal perspective was taken for a prevalence-based assessment of
      the direct (total resources consumed by outpatients and inpatients) and indirect
      (due to morbidity, invalidity, and premature death, using the human capital
      approach) costs. The results showed the total costs were 21 million US dollars
      per 100000 population in the year 1993 (47% direct, 53% indirect costs). The
      largest components were the direct costs of inpatient care and indirect costs due
      to premature death (each approximately 25% of the total). Trends showed a large
      increase in direct costs (+9% per year, constant dollars). Indirect costs
      stabilized or decreased slightly due to the reduction of work losses.
      CONCLUSIONS: Today's medicine and preventive measures have proven effective for
      ischaemic heart disease, although such remedies have required increasingly large
      financial resources. However, society benefits because indirect costs decrease,
      although this gain does not compensate for all direct costs.

PMID- 9243144
TI  - PTCA registry of German community hospitals. Arbeitsgemeinschaft Leitender
      Kardiologischer Krankenhausarzte (ALKK) Study Group.
AB  - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is widely used,
      but no quality control has been systematically performed as yet. METHODS: A
      registry of all PTCA procedures has been established since October 1992 for the
      majority of the German community hospitals performing PTCA, representing about
      one third of all PTCA activity in Germany. Baseline demographic data, indication
      for PTCA, primary success and in-hospital clinical events were recorded. Each
      centre was visited at regular intervals to assure completeness and reliability of
      the data. RESULTS: Of 52453 procedures performed from October 1992 to December
      1994 the catheter laboratory and discharge forms were 99.7% and 98.1% complete,
      respectively. In 85.9% a single lesion was dilated per procedure, but 48.7% of
      the patients had multivessel disease. The success rate was 66.5% in complete
      occlusions (residual stenosis < 70%) and 91.2% in non-occluded vessels (residual
      stenosis < 50%). Abrupt vessel closure occurred in 3.4%, of which 77.5% could be
      recanalized by repeat intervention. In procedures not done for acute myocardial
      infarction, the in-hospital mortality was 0.52%, the procedure-related mortality
      0.37%. In 3.02% of all patients a severe complication occurred (procedure-related
      death, myocardial infarction or emergency bypass surgery). CONCLUSION: Complete
      recording of all PTCA procedures is feasible even on a nationwide basis. This is
      a pre-requisite for continuous quality control. The reporting of the procedures
      by itself very probably, has an impact on the quality which is, however, not
      measurable quantitatively.

PMID- 9243145
TI  - More favourable haemodynamic effects from metoprolol than from captopril in
      patients with dilated cardiomyopathy.
AB  - AIM: The object of this study was to investigate and compare the haemodynamic
      effects of treatment with a beta receptor blocker (metoprolol) or an angiotensin
      converting-enzyme inhibitor (captopril) in 54 patients with idiopathic dilated
      cardiomyopathy. METHOD: All patients had cardiac catheterization performed at
      rest and during exercise, before and after 3 months of treatment. RESULTS: The
      mean dose of metoprolol was 135 mg.day-1 and of captopril 98 mg.day-1. After
      treatment there was a significant reduction in left ventricular filling pressure
      both at rest (from 16 to 12 mmHg) and during exercise (from 27 to 20 mmHg) in the
      metoprolol group. In the captopril group a significant reduction was seen only
      during exercise (25 to 20 mmHg), compared to baseline. The stroke volume
      increased significantly after 3 months of therapy in the metoprolol group, both
      at rest (53 to 70 ml) and during exercise (56 to 79 ml). In the captopril group
      the increase reached significance only during exercise (72 to 79 ml). Cardiac
      output was maintained in both groups. CONCLUSION: There were positive effects on
      left ventricular function in the metoprolol group as well as in the captopril
      group. Metoprolol reduced left ventricular filling pressure at rest and increased
      stroke volume both at rest and during exercise significantly more than captopril.

PMID- 9243146
TI  - Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome.
AB  - AIMS: The aim of the study was to determine the epidemiology of out-of-hospital
      cardiac arrests of non-cardiac origin and survival following resuscitation, using
      the Utstein method of data collection. METHODS AND RESULTS: The study was of
      prospective cohort design and was conducted in a middle-sized urban city
      (population 525000) served by a single emergency medical services system.
      Consecutive out-of-hospital cardiac arrests of non-cardiac origin occurring
      between 1 January 1994 and 31 December 1995 were included. Survival from cardiac
      arrest to hospital discharge, and factors associated with survival were
      considered as main outcome measures. Of the 809 patients, 276 (34.1%) had a
      cardiac arrest of non-cardiac origin. The mean (SD) age of the patients was 49.8
      (20.9) years. Resuscitation was attempted in 204 cases, 82 of whom (40.2%) were
      hospitalized alive and 23 (11.3%) were discharged. Thirteen (56.5%) of the
      survivors were discharged neurologically intact or with mild disability (overall
      performance category I or II). The survivors, during the study period, who
      suffered an out-of-hospital cardiac arrest of non-cardiac origin comprised 19.2%
      of all out-of-hospital cardiac arrest survivors. Trauma (62), non-traumatic
      bleeding (36), intoxication (31), near drowning (22) and pulmonary embolism (18)
      were the most common aetiologies, comprising 61.2% of cases. The non-cardiac
      aetiology was suspected pre-hospital in 176 (63.8%) cases; in the remaining
      cases, the aetiology was revealed only after in-hospital investigations or
      autopsy. In a logistic regression model, time interval to first responding unit,
      collapse outside the home, and aetiologies of near-drowning, airway obstruction,
      intoxication and convulsions were associated with survival. CONCLUSIONS: These
      results indicate that sudden out-of-hospital cardiac arrest more often has a non
      cardiac cause than previously believed. Although survival is not as likely as
      from cardiac arrest of cardiac origin, since non-cardiac-cause survivors comprise
      one fifth of all out-of-hospital cardiac arrest survivors, resuscitation efforts
      are worthwhile.

PMID- 9243147
TI  - Dispersion of ventricular repolarization in dilated cardiomyopathy.
AB  - OBJECTIVE: Increased dispersion of ventricular repolarization has been shown to
      be a marker for increased risk of ventricular tachyarrhythmias in various cardiac
      disorders. The present study is aimed at comparing the values of four dispersion
      indices in four clinical groups: normal subjects (n = 23), patients with
      intraventricular conduction defects (QRS > 0.12 s) without underlying cardiac
      disease (n = 30), patients with dilated cardiomyopathy (n = 36), and patients
      with both dilated cardiomyopathy and ventricular conduction defects (n = 18).
      METHODS: On an averaged cycle from a 10 s record of 15 simultaneous leads (12
      lead ECG and XYZ leads), and after interactive editing, four intervals were
      computed: JTapex, JTend, QTapex and QTend. For each interval, the dispersion is
      defined as the difference between the maximal and minimal values across the 15
      leads. RESULTS: The mean values of all four dispersion indices were significantly
      smaller in the normal group than in the three other groups (P < 0.001). Among
      patients with dilated cardiomyopathy, those with intraventricular conduction
      defects had significantly higher dispersion values than those without, even
      disregarding the QRS duration (P < 0.01). Thus, patients with both dilated
      cardiomyopathy and ventricular conduction defects have larger dispersion values
      than patients with ventricular conduction defects alone (P < 0.01) and than those
      with dilated cardiomyopathy without intraventricular conduction defects.
      CONCLUSION: Dispersion of ventricular repolarization is increased in patients
      with dilated cardiomyopathy, especially in those with ventricular conduction
      defects, suggesting that they are at higher risk of arrhythmic events.

PMID- 9243148
TI  - The structural arteriolar changes in diabetes mellitus and essential
      hypertension. The relative contribution of ageing and high blood pressure.
AB  - AIM: To evaluate the relative contribution of blood pressure, non-insulin
      dependent diabetes mellitus and ageing on arteriolar structural changes in
      essential hypertension and diabetes mellitus. POPULATION AND METHODS: One hundred
      subjects, 25 with hypertension (A), 25 with hypertension and diabetes (B), 25
      with diabetes (C) and 25 healthy subjects (D). Blood pressure average values,
      obtained with non-invasive monitoring, and minimal vascular resistance,
      calculated with strain-gauge plethysmography, were statistically correlated.
      Multiple regression analysis was performed to assess the contribution of blood
      pressure and age. RESULTS: Minimal vascular resistance was higher in A, B and C
      than in D, and higher in B than in A and C. The coefficient of blood pressure in
      the multiple regression analysis was significant for all the parameters in A and
      B but not in C and D; that of age was significant only in A and only for the
      average values of mean and diastolic blood pressure. CONCLUSION: Hypertension and
      diabetes show arteriolar structural changes of similar gravity. Age does play a
      role in hypertension but a smaller one than that played by blood pressure. In
      hypertension and diabetes the lack of significance of the contribution of age to
      the correlation between minimal vascular resistance and pressure could be
      ascribed to other neurohumoral factors. These factors play a much more important
      role in diabetes; where neither blood pressure nor age show any correlation with
      high vascular resistance.

PMID- 9243149
TI  - Streptokinase vs alteplase in massive pulmonary embolism. A randomized trial
      assessing right heart haemodynamics and pulmonary vascular obstruction.
AB  - OBJECTIVE: The aim of the study was to test the efficacy of recombinant tissue
      plasminogen activator and streptokinase in massive pulmonary embolism, the
      primary endpoints being haemodynamic improvement and thrombus lysis, and the
      secondary endpoints efficacy and safety. DESIGN: Fifty patients with massive
      pulmonary embolism were randomly allocated either to a 100 mg 2 h infusion of
      recombinant tissue plasminogen activator followed by a 20 IU.kg-1.h-1 infusion of
      heparin, or to a 100,000 IU.h-1 12 h infusion of streptokinase after a initial
      bolus of 250,000 IU over 15 min, followed by heparin infusion of 10 IU.kg-1.h-1.
      Total pulmonary resistance and right ventricular ejection fraction were monitored
      over a 12 h period. Pulmonary vascular obstruction was assessed at 24 to 48 h and
      10 days after thrombolytic therapy. RESULTS: Thrombolysis occurred more rapidly
      with recombinant tissue plasminogen activator than with streptokinase, but
      without any significant difference in terms of right heart haemodynamics at 12 h
      or in improvement of pulmonary vascular obstruction at 24-48 h or at 10 days.
      There was no significant difference in bleeding complication rates and no
      patients suffered intracranial haemorrhage. CONCLUSION: These results proved
      that, when the full dose of streptokinase has been given over 12 h, its efficacy
      is as good as that of 2 h of recombinant tissue plasminogen. A further trial
      aimed at comparing recombinant tissue plasminogen activator and streptokinase
      infused over a 2 h period is needed to determine whether a similar efficacy can
      be obtained.

PMID- 9243150
TI  - New diagnostic criteria for infective endocarditis. A study of sensitivity and
      specificity.
AB  - OBJECTIVE: The purpose of this study was to determine the sensitivity and
      specificity of new criteria proposed by Duke University for case definition of
      infective endocarditis as compared to the previously accepted Von Reyn criteria.
      PATIENTS: A total of 143 consecutive suspected cases of infective endocarditis in
      137 febrile patients were included. Of these, 69 had infective endocarditis,
      pathologically proven in 28, but with only a clinical diagnosis in 41. In the
      remaining 74 cases, the diagnosis of infective endocarditis was rejected after a
      follow-up of at least 3 months. RESULTS: The sensitivity of Duke's criteria was
      significantly higher, both when patients with possible infective endocarditis
      were considered as true-positive (definition 1; 100% vs 69%, P < 0.001) and when
      possible cases were considered as rejected (definition 2; 76% vs 51%, P < 0.01).
      Specificity was very high with both criteria: 92% Von Reyn vs 88% Duke (ns) with
      definition 1 and 99% Von Reyn vs 97% Duke (ns) with definition 2. The overall
      accuracy of the Duke criteria in the entire population was significantly higher
      with both definitions (0.94 vs 0.81 definition 1, P < 0.001; 0.87 vs 0.75, P =
      0.015 definition 2). CONCLUSION: Duke's criteria for defining infective
      endocarditis has been shown to be more sensitive than previously adopted
      criteria, while maintaining a high degree of specificity. Therefore, they must be
      accepted as a substitute for previous criteria.

PMID- 9243151
TI  - 25 years of aortic valve replacement using mechanical valves. Risk factors for
      early and late mortality.
AB  - This study describes the changes that have taken place in patient characteristics
      in 25 years of aortic valve replacement using mechanical valves, and looks for
      risk factors for early and late mortality. During this period, 1449 mechanical
      valves were implanted. Overall early mortality (< 30 days) was 5.3% and for
      aortic valve replacement without concomitant procedures 3.9%. Overall survival
      rates at 5, 10 and 15 years were 80%, 63% and 49%, respectively. Despite an
      increased proportion of higher risk patients (older age, more reoperations, more
      concomitant coronary bypass surgery) survival rates improved throughout the study
      period. Early mortality was related to an early year of operation, urgency,
      reoperation and concomitant surgery to the tricuspid valve or ascending aorta.
      Late mortality was higher for patients of older age, with an early year of
      operation, male gender, concomitant coronary bypass surgery, mitral valve surgery
      or replacement of the ascending aorta. Aortic regurgitation did not have a major
      influence on early nor late mortality. The improvement in early and late
      mortality in more recent years was largely the result of the introduction of
      cardioplegia. A changing, non-proportional effect was observed for several risk
      factors during the follow-up period. This study illustrates the changes and
      improvements in medical care that have taken place in patients requiring aortic
      valve replacement.

PMID- 9243152
TI  - Coronary vasodilation without myocardial erection. Simultaneous haemodynamic,
      echocardiographic and arteriographic findings during adenosine and dipyridamole
      infusion.
AB  - AIM: The aim of this study was to evaluate simultaneously echocardiographic,
      haemodynamic and angiographic changes that occur during adenosine and
      dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This
      would assess whether deterioration in left ventricular haemodynamics during
      vasodilator agent infusion is influenced by vasodilation per se, or the
      development of myocardial ischaemia. METHODS AND RESULTS: We performed adenosine
      (140 micrograms.kg-1.min-1 over 4 min) and dipyridamole (up to 0.84 mg.kg-1 over
      10 min) stress echocardiography tests, together with angiographic and
      haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty.
      In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after
      angioplasty. The criterion for echocardiography test positivity was the
      appearance of a new transient regional wall motion abnormality. Coronary
      angiograms were analysed with quantitative coronary arteriography. Adenosine and
      dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients
      before angioplasty, respectively (P = ns). In the echocardiography-positive
      patients, the percent diameter stenosis was significantly (P < 0.05) tighter
      stenosis than in the echocardiography-negative patients (adenosine, 66.6 +/- 8.3%
      vs 58.0 +/- 8.9%; dipyridamole, 69.2 +/- 7.1% vs 57.7 +/- 7.6%). During both
      tests, left ventricular end-diastolic pressure significantly increased (P < 0.05)
      in echocardiography-positive patients (adenosine, 9.8 +/- 2.7 mmHg to 13.5 +/-
      4.1 mmHg; dipyridamole, 10.1 +/- 2.8 mmHg to 14.1 +/- 4.3 mmHg), but not in
      echocardiography-negative patients. In the patients who had undergone successful
      angioplasty (reduction to < 50% diameter stenosis), both adenosine and
      dipyridamole confirmed the arteriographic success of the procedure
      (echocardiography negative in all patients). In this group of patients, no
      significant change was observed in left ventricular end-diastolic pressure during
      adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either
      adenosine or dipyridamole was accompanied by an obvious increase in left
      ventricular end-diastolic pressure only in patients with induced wall motion
      abnormalities. Coronary vasodilation per se has no significant effect on left
      ventricular end-diastolic pressure when no ischaemia is induced, disproving any
      clinically significant 'erectile' and adverse effects of coronary vasodilation
      per se.

PMID- 9243153
TI  - The apical long-axis rather than the two-chamber view should be used in
      combination with the four-chamber view for accurate assessment of left
      ventricular volumes and function.
AB  - BACKGROUND: Most biplane methods for the echocardiographic calculation of left
      ventricular volumes assume orthogonality between paired views from the apical
      window. Our aim was to study the accuracy of biplane left ventricular volume
      calculations when either the apical two-chamber or long-axis views are combined
      with the four-chamber view. The left ventricular volumes calculated from three
      dimensional echocardiographic data sets were used as a reference. Twenty-seven
      patients underwent precordial three-dimensional echocardiography using rotational
      acquisition of planes at 2-degree intervals, with ECG and respiratory gating. End
      diastolic and end-systolic left ventricular volumes and ejection fraction on
      three-dimensional echocardiography were calculated by (1) Simpson's methods (3DS)
      at 3 mm short-axis slice thickness (reference method) and by (2) biplane ellipse
      from paired views using either apical four- and two-chamber views (BE-A) or
      apical four- and long-axis views (BE-B). Observer variabilities were studied by
      the standard error of the estimate % (SEE) in 19 patients for all methods.
      RESULTS: The spatial angles (mean +/- SD) between the apical two-chamber, long
      axis and four-chamber views were 63.3 degrees +/- 19.7 and 99.1 degrees +/- 25.6,
      respectively. The mean +/- SD of end-diastolic and end-systolic left ventricular
      volumes (ml) and ejection fraction (%) by 3DS were 142.2 +/- 60.9, 91.8 +/- 59.6
      and 39.6 +/- 17.5, while that by BE-A were 126.7 +/- 60.4, 84.0 +/- 57.9 and 39
      +/- 17 and by BE-B were 134.3 +/- 62.4, 88.6 +/- 59.7 and 39.1 +/- 16.7,
      respectively. BE-B intra-observer (8.4, 6.7 and 3.5) and inter-observer (9.8,
      11.5 and 5.4) SEE for end-diastolic and end-systolic left ventricular volumes
      (ml) and ejection fraction (%), respectively, were smaller than that for BE-A
      (10.8, 8.8 and 4.1 and 11.4, 14.7 and 6.1, respectively). There was excellent
      correlation between 3DS and BE-A (r = 0.99, 0.98 and 0.98) and BE-B (0.98, 0.98
      and 0.98) for calculating end-diastolic and end-systolic left ventricular volume
      and ejection fractions, respectively. There were no significant differences
      between BE-A and BE-B with 3DS for end-diastolic and end-systolic left
      ventricular volume and ejection fraction calculations (P = 0.2, 0.3 and 0.4 and P
      = 0.5, 0.5 and 0.4, respectively). There were closer limits of agreement (mean +/
      2 SD) between 3DS and BE-B 7.9 +/- 18.8, 3.2 +/- 14.2 and 0.8 +/- 5.8 than that
      between 3DS and BE-A 15.5 +/- 19.6, 7.8 +/- 16.2 and 1.1 +/- 7.4 for calculating
      end-diastolic and end-systolic left ventricular volume and ejection fractions,
      respectively. CONCLUSION: Both apical two-chamber and apical long-axis views are
      not orthogonal to the apical four-chamber view. Observer variabilities of BE-B
      were smaller than that for BE-A. BE-A and BE-B have excellent correlation and non
      significant differences with 3DS for left ventricular volume and ejection
      fraction calculations. There were closer limits of agreement between BE-B with
      3DS for left ventricular volume and ejection fraction calculations than that
      between BE-A and 3DS. Therefore, we recommend the use of the apical long-axis
      rather than the two-chamber view in combination with the four-chamber view for
      accurate biplane left ventricular volume and ejection fraction calculations.

PMID- 9243154
TI  - Coronary sinus lactates, coronary artery disease and normal coronary arteries.

PMID- 9243155
TI  - Smoking cessation as a rigorous primary intervention for coronary events in
      middle-aged men. A commentary based on the WOSCOP findings. West of Scotland
      Coronary Prevention Study.

PMID- 9243156
TI  - Moving beyond lumenology.

PMID- 9243157
TI  - Multiple restenoses following PTCA.

PMID- 9243158
TI  - The epidemiology of Q fever.

PMID- 9243159
TI  - The syndrome of right bundle branch block, persistent ST segment elevation and
      sudden cardiac death. Which is the histological substrate?

PMID- 9243160
TI  - Clinical presentation and surgical results in a patient who has multiple
      congenital heart defects.

PMID- 9243161
TI  - Vectorcardiographic monitoring of ST segment changes during transient hypotension
      following thrombolysis with streptokinase.

PMID- 9243162
TI  - A case of infective endocarditis complicated with anterior mitral valve leaflet
      abscess.

PMID- 9243163
TI  - Analysis of sweat evaporation from clothing materials by the ventilated sweat
      capsule method.
AB  - The local influence of three clothing materials i.e. silk, cotton and nylon, in
      (1) full or (2) partial skin contact or (3) at 3 mm from the skin, on sweat
      evaporation from the chest skin surface of human subjects was studied. The
      hygrometer-ventilated capsule method was used and sweating was induced at ambient
      thermoneutrality by a central heat load following lower-leg immersion in water at
      43 degrees C. The presence of clothing delayed the rise in capsule relative
      humidity (CRH) induced by heat loading. During the first 6 min of heating, CRH
      rose more steeply with clothing that was in full skin contact than with clothing
      that had partial or no contact. The rate of decrease in CRH from 1 min to 6 min
      after heating was not influenced by the presence of clothing or by the different
      degrees of skin contact. The subsequent return of CRH to the pre-heating level
      was delayed most by cotton, less by silk and least by nylon. For silk and nylon,
      partial contact with the skin prolonged the return to control conditions, as
      compared with full skin contact.

PMID- 9243164
TI  - Training-induced increases in sea level VO2max and endurance are not enhanced by
      acute hypobaric exposure.
AB  - The present study used untrained subjects to examine the effect of acute
      hypobaric exposure during endurance training on subsequent exercise performance
      at sea level. Two groups, each of nine subjects, completed 5 weeks of endurance
      training [cycle ergometer exercise for 45 min, three times per week at a heart
      rate corresponding to 70% of that achieved at the maximal O2 consumption (VO2max)
      either at sea level or at high altitude] in a hypobaric chamber, under either
      normobaric [sea level, SL; 750 mmHg (100 kPa) approximately 90 m] or hypobaric
      [altitude, ALT; 554 mmHg (73.4 kPa) approximately 2500 m] conditions and the
      changes in SL VO2max, SL endurance time and peak blood lactate during the
      endurance test compared. While each group showed increases in both SL VO2max
      (approximately 12%) and SL endurance time (approximately 71%), there were no
      significant differences between the groups [SL VO2max, mean (SE)-SL group: pre
      training = 42.4 (3.5), post-training = 46.1 (3.5) ml.kg-1.min-1, P < 0.005; ALT
      group: pre-training = 40.8 (2.6), post-training = 47.2 (3.4) ml.kg-1.min-1, P <
      0.01; SL endurance time-SL group: pre-training 7.1 (1.5), post-training 11.8
      (2.9) min, P < 0.01; ALT group: pre-training = 7.5 (0.6), post-training = 13.3
      (1.4) min, P < 0.001]. Peak blood lactate during the endurance test was not
      altered by either training regimen. It is concluded that acute exposure of
      untrained subjects to hypobaric hypoxia during endurance training has no
      synergistic effect on the degree of improvement in either SL VO2max or endurance
      time.

PMID- 9243165
TI  - Anaerobic contribution to the time to exhaustion at the minimal exercise
      intensity at which maximal oxygen uptake occurs in elite cyclists, kayakists and
      swimmers.
AB  - Using 23 elite male athletes (8 cyclists, 7 kayakists, and 8 swimmers), the
      contribution of the anaerobic energy system to the time to exhaustion (t(lim)) at
      the minimal exercise intensity (speed or power) at which maximal oxygen uptake
      (VO2max) occurs (IVO2max) was assessed by analysing the relationship between the
      t(lim) and the accumulated oxygen deficit (AOD). After 10-min warming up at 60%
      of VO2max, the exercise intensity was increased so that each subject reached his
      IVO2max in 30 s and then continued at that level until he was exhausted. Pre
      tests included a continuous incremental test with 2 min steps for determining the
      IVO2max and a series of 5-min submaximal intensities to collect the data that
      would allow the estimation of the energy expenditure at IVO2max. The AOD for the
      t(lim) exercise was calculated as the difference between the above estimation and
      the accumulated oxygen uptake. The mean percentage value of energy expenditure
      covered by anaerobic metabolism was 15.2 [(SD 6)%, range 8.9-24.1] with
      significant differences between swimmers and kayakists (16.8% vs 11.5%, P < or =
      0.05) and cyclists and kayakists (16.4% vs 11.5%, P < or = 0.05). Absolute AOD
      values ranged from 26.4 ml.kg-1 to 83.6 ml.kg-1 with a mean value of 45.9 (SD 18)
      ml.kg-1. Considering all the subjects, the t(lim) was found to have a positive
      and significant correlation with AOD (r = 0.62, P < or = 0.05), and a negative
      and significant correlation with VO2max (r = -0.46, P < or = 0.05). The data
      would suggest that the contribution of anaerobic processes during exercise
      performed at IVO2max should not be ignored when t(lim) is used as a supplementary
      parameter to evaluate specific adaptation of athletes.

PMID- 9243166
TI  - Changes in the mechanical properties of human and amphibian muscle after
      eccentric exercise.
AB  - Following a series of eccentric contractions, that is stretching of the muscle
      while generating active tension, the length-tension relationship of isolated
      amphibian muscle has been shown to shift towards longer muscle length (Katz 1939;
      Wood et al. 1993). Here we report observations of electrically stimulated ankle
      extensor muscles of nine human subjects, demonstrating a similar shift in optimum
      angle for torque generation [3.9 (1.5) degrees] following exercise on an inclined
      treadmill that involved eccentric contractions in one leg. (All values are means
      with the SEMs in parentheses). The shift in the unexercised, control leg was
      significantly less [mean 0.4 (0.7) degree P < 0.05]. Correlated with this shift
      was a drop in torque [25.1 (5.6)% for the experimental leg; 1.6 (0.7)% for the
      control leg, P < 0.002]. Optimum angles returned to pre-exercise values by 2 days
      post-exercise, while torque took a week to recover. A similar shift in optimum
      length [12 (1.3)% of rest length] was obtained for five toad (Bufo marinus)
      sartorius muscles subjected to 25 eccentric contractions. Isometrically
      contracted control muscles showed a smaller shift [3.5 (1.6)%, n = 5].
      Accompanying the shift was a drop in tension of 46 (3)% after the eccentric
      contractions [control isometric, 23 (6)%, P < 0.0001]. By 5 h after the eccentric
      contractions the shift had returned to control values, while tension had not
      recovered. When viewed with an electron microscope, sartorius muscles fixed
      immediately after the eccentric contractions exhibited many small, and a few
      larger, regions of myofilament disruption. In muscles fixed 5 h after the
      contractions, no small regions of disruption were visible, and the number of
      large regions was no greater than in those muscles fixed immediately after the
      eccentric contractions. These disruptions are interpreted as the cause of the
      shift in length-tension relationship.

PMID- 9243167
TI  - Resistance exercise training and the orthostatic response.
AB  - Resistance exercise has been suggested to increase blood volume, increase the
      sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and
      decrease leg compliance, all factors that are expected to improve orthostatic
      tolerance. To further test these hypotheses, cardiovascular responses to standing
      and to pre-syncopal limited lower body negative pressure (LBNP) were measured in
      two groups of sedentary men before and after a 12-week period of either exercise
      (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted
      of nine isotonic exercises, four sets of each, 3 days per week, stressing all
      major muscle groups. After exercise training, leg muscle volumes increased (P <
      0.05) by 4-14%, lean body mass increased (P = 0.00) by 2.0 (0.5) kg, leg
      compliance and BARO were not significantly altered, and the maximal LBNP
      tolerated without pre-syncope was not significantly different. Supine resting
      heart rate was reduced (P = 0.03) without attenuating the heart rate or blood
      pressure responses during the stand test or LBNP. Also, blood volume (125I and
      51Cr) and red cell mass were increased (P < 0.02) by 2.8% and 3.9%, respectively.
      These findings indicate that intense resistance exercise increases blood volume
      but does not consistently improve orthostatic tolerance.

PMID- 9243168
TI  - A comparison of the effects of agonist and antagonist muscle fatigue on
      performance of rapid movements.
AB  - The aim of this study was to investigate the effects of agonist and antagonist
      muscle fatigue on the performance of rapid, self-terminating movements. Six
      subjects performed rapid, consecutive elbow flexion and extension movements
      between two targets prior to and after fatiguing either the elbow flexor or elbow
      extensor muscles. The experiments demonstrated consistent results. Agonist muscle
      fatigue was associated with a decrease in peak velocity and peak deceleration,
      while a decrease in peak acceleration was particularly prominent. Antagonist
      muscle fatigue, however, was associated with a decrease in peak deceleration,
      while a decrease in both the peak velocity and peak acceleration was modest and,
      in some tests, non-significant. The relative acceleration time (i.e. acceleration
      time as a proportion of the total movement time) increased when agonists were
      fatigued, but decreased when antagonists were fatigued. Taken together, these
      results emphasize the mechanical roles of the agonist and antagonist muscles;
      namely, the fatigue of each muscle group particularly affected the movement phase
      in which that group accelerated a limb, while changes of the movement kinematics
      pattern provided more time for action of the fatigued muscles. In addition, the
      results presented suggest that agonist muscle fatigue affects movement velocity
      more than antagonist muscle fatigue, even in movements that demonstrate
      prominently both mechanical and myoelectric activity of the antagonist muscles,
      such as rapid, self-terminating movements.

PMID- 9243169
TI  - Effect of sodium citrate on performance and metabolism of human skeletal muscle
      during supramaximal cycling exercise.
AB  - The aim of this study was to examine whether the alkalosis-induced improvement in
      supramaximal performance could be explained by a less-altered muscle metabolic
      status. Eight subjects first performed exhausting exercise at 120% peak oxygen
      uptake after ingesting either a placebo (PLC) or sodium citrate (CIT) at a dose
      of 0.5 g.kg-1 body mass to determine exhaustion time (texh). They then, performed
      exercise (Lim-EX) at the same relative intensity lasting PLCtexh minus 20 s in
      both treatments. Samples were taken from vastus lateralis muscle at rest (90-min
      after the ingestion) and at the end of Lim-EX. Arterial blood samples were
      obtained at rest (immediately prior to and 90 min after ingesting the drug) and
      during the 20-min post-exercise recovery. The texh was significantly increased by
      CIT [PLC 258 (SD 29) s, CIT 297 (SD 45) s]. The CIT raised the rest [citrate] in
      blood [PLC 0.11 (SD 0.01) mmol.l-1, CIT 0.34 (SD 0.07) mmol.l-1] and in muscle
      [PLC 0.78 (SD 0.23) mmol.kg-1 dry mass, CIT 1.00 (SD 0.21) mmol.kg-1 dry mass].
      Resting muscle pH and buffering capacity were unchanged by CIT. The same fall in
      muscle pH was observed during Lim-EX in the two conditions. This was associated
      with similar variations in both the cardio-respiratory response and muscle energy
      and metabolism status in spite of a better blood acid-base status after CIT.
      Thus, CIT would not seem to allow the alkalinization of the muscle cytosolic
      compartment. Though sodium citrate works in a similar way to NaHCO3 on plasma
      alkalinization and exercise performance, the exact nature of the mechanisms
      involved in the delay of exhaustion could be different and remains to be
      elucidated.

PMID- 9243170
TI  - Posture control after prolonged exercise.
AB  - The perturbations of equilibrium after prolonged exercise were investigated by
      dynamic posturography on nine well-trained subjects (four athletes and five
      triathletes). A sensory organization test, where the platform and visual surround
      were either stable or referenced to the subject's sway with eyes open or closed,
      was performed before and after a 25-km run (average time 1 h 44 min) by the nine
      subjects. In addition, the same test was performed on the five triathletes only,
      before and after ergocycle exercise of identical duration (i.e. ergocycle time =
      running time). The results showed that the ability to maintain postural stability
      during conflicting sensory conditions decreased after exercise, with some
      differences depending on the kind of exercise. Sensory analysis revealed that the
      subjects made less effective use of vestibular inputs after running than after
      cycling (P < 0.05). Adaptation to prolonged stimulation of proprioceptive,
      vestibular and visual inputs had probably occurred in the integrating centres
      during exercise. This adaptation was maintained during the recovery period and
      could explain the postexercise balance disorders. Other mechanisms such as
      impairment of motor efferents or haemodynamic changes should not be excluded.

PMID- 9243171
TI  - Standing strength training of the ankle plantar and dorsiflexors in older women,
      using concentric and eccentric contractions.
AB  - Many studies have reported strength gains in older adults following high
      intensity resistance training. However, the muscle contraction types examined
      have been primarily isometric (static) or concentric (CONC; shortening). Less is
      known about how eccentric (ECC) strength in older adults responds to training or
      about the efficacy of ECC contractions as training stimuli in these subjects,
      even though muscle contractions of this type are performed in most training
      regimens and daily physical activities. In this study, 15 physically active,
      healthy older women [68 (5) years; mean (SD)] completed an 8-week resistance
      training program of two sessions per week. Training consisted of three sets of
      eight repetitions of CONC ankle plantar flexion (PF) and ECC dorsiflexion (DF),
      at greater than 80% of the initial peak torque, in a standing position only.
      Subjects were tested in standing and supine positions for: (1) strength over a
      range of 10 degrees DF to 20 degrees PF for both CONC and ECC; DF and PF (2)
      passive resistive torque of the plantar flexors at 6 degrees/s; and (3) DF and PF
      rate of torque development. All strength testing and training was done at 30
      degrees/s. Significant increases (P < 0.01) were found for both CONC DF
      (increases 30%) and ECC DF (increases 17%) peak torque in the standing position.
      No significant changes occurred for DF strength as measured with the subjects in
      the supine position, PF strength in either position, passive resistive torque, or
      rate of torque development. In summary, strength gains occurred only in the
      dorsiflexors, which were trained using ECC contractions. Improvements in DF
      strength were specific to the position of training, which has implications for
      the transferability of strength gains to functional tasks such as maintaining
      gait.

PMID- 9243172
TI  - Thermal status of wet-suited divers using closed circuit O2 apparatus in sea
      water of 17-18.5 degrees C.
AB  - A wet suit may not provide adequate thermal protection when diving in moderately
      cold water (17-18 degrees C), and any resultant mild hypothermia may impair
      performance during prolonged diving. We studied heat exchange during a dive to a
      depth of 5 m in sea water (17-18.5 degrees C) in divers wearing a full wet suit
      and using closed-circuit oxygen breathing apparatus. Eight fin swimmers dived for
      3.1 h and six underwater scooter (UWS) divers propelled themselves through the
      water for 3.7 h. The measurements taken throughout the dive were the oxygen
      pressure in the cylinder and skin and rectal temperatures (Tre). Each subject
      also completed a cold score questionnaire. The Tre decreased continuously in all
      subjects. Oxygen consumption in the fin divers (1.40 l.min-1) was higher than
      that of the UWS divers (1.05 l.min-1). The mean total insulation was 0.087 degree
      C.m2.W-1 in both groups. Mean body insulation was 37% of the total insulation
      (suit insulation was 63%). The reduction in Tre over the 1st hour was related to
      subcutaneous fat thickness. There was a correlation between cold score and Tre at
      the end of 1 h, but not after that. A full wet suit does not appear to provide
      adequate thermal protection when diving in moderately cold water.

PMID- 9243173
TI  - Trunk muscle fatigue and associated EMG changes during a dynamic iso-inertial
      test.
AB  - This study was designed to investigate the relationship between trunk muscle
      fatigue and associated changes in the electromyographic (EMG) signals during a
      dynamic iso-inertial test. Eleven subjects performed dynamic trunk
      flexion/extension movements against 40% maximum voluntary contraction (MVC)
      torque until exhaustion in a tri-axial trunk dynamometer. EMG parameters in the
      time and frequency domain were studied by analysing changes of the signal
      amplitudes and the spectral density (using the zero-crossing-rate and the median
      frequency). The kinematics of the movement were analysed according to the
      movement velocities and the deviations from the required movement plane. The
      flexion and extension velocities decreased from the beginning to the end of the
      test. Movement deviations from the sagittal plane into the frontal and transverse
      plane increased with increasing test duration, as did the EMG amplitude. The
      median frequency during periods with maximum muscle activity decreased, as did
      the zero-crossing-rate. The increase in amplitude and decrease in median
      frequency were more pronounced in the trunk flexors than in the trunk extensors.
      The parameters of median frequency, zero-crossing-rate and amplitude seem to be
      sensitive identifiers of muscle fatigue during well-controlled dynamic
      contractions. While the kinematic data did not yield any information on the
      mechanisms of the fatigue, changes in the EMG parameters demonstrated that the
      duration of the test was limited by the fatigue of the trunk flexors.

PMID- 9243174
TI  - Habitual physical activity and peak anaerobic power in elderly women.
AB  - The aim of this study was to investigate the relationship between maximal
      anaerobic power (Pmax) and corresponding optimal velocity (Vopt) and habitual
      physical activity (PA) on the one hand and with maximal oxygen consumption
      (VO2max) on the other hand, in elderly women. Twenty-nine community dwelling,
      healthy women aged 66-82 years participated in the study. PA was evaluated using
      the Questionnaire d'Activite Physique Saint-Etienne (QAPSE) and expressed using
      two QAPSE activity indices: mean habitual daily energy expenditure (MHDEE) and
      daily energy expenditure corresponding to leisure time sports activities (sports
      activity). The subjects' Pmax and Vopt were measured while they cycled on a
      friction-loaded non-isokinetic cycle ergometer. Pmax was expressed relative to
      body mass [Pmax/kg(W.kg-1)], and relative to the mass of two quadriceps muscles
      [Pmax/Quadr(W.kg-1Quadr)]. A negative relationship between Pmax/kg (Spearman's r
      = -0.56; P < 0.01), Pmax/Quadr (r = -0.53; P < 0.01) and Vopt (r = -0.45; P <
      0.05) and age was found. Pmax/kg was positively associated with MHDEE (r = 0.51;
      P < 0.01) and sports activity (r = 0.58; P < 0.01), as were Pmax/Quadr and Vopt
      (r = 0.55; P < 0.01 and r = 0.54; P < 0.01, respectively). Pmax/kg, Pmax/Quadr
      and Vopt correlated positively with VO2max. The positive relationship between
      ergometer measurements and PA indices was similar to that between VO2max and PA.
      Pmax/kg was, moreover, closely related to Vopt (r = 0.77; P < 0.001). When a
      multiple stepwise regression analysis was used to select the variables
      influencing ergometer measurements, MHDEE contributed significantly to Pmax/kg
      variance, whereas sports activity contributed to Pmax/Quadr and Vopt variances.
      In conclusion, the data from this cross-sectional study suggest that in healthy
      elderly women habitual PA, and especially leisure time PA, alleviates the decline
      of the Pmax of the quadriceps muscles.

PMID- 9243175
TI  - Evidence of differential renal dysfunctions during exercise in men.
AB  - Post-exercise proteinuria is a common phenomenon in healthy subjects. Previous
      studies have used albumin (Alb) and beta 2-microglobulin (beta 2-m) molecules as
      representatives of high- and low-molecular-weight proteins. Recently, more
      specific markers of the human kidney proximal tubule have been used to identify
      the precise site of alterations. Active male subjects underwent two strenuous
      runs, one 400-m run and one 3000-m run. Urine was collected from the subjects
      before and after each event. Total protein (TP), Alb, alpha 1-microglobulin
      (alpha 1-m), beta 2-m, intestinal alkaline phosphatase (IAP), tissue-nonspecific
      alkaline phosphatase (TNAP) and N-acetyl-beta-D-glucosaminidase (NAG) were
      determined for each sample. The short-distance run (400 m) resulted in the
      largest increases (P < or = 0.05) in TP (31-fold), Alb (100-fold) and beta 2-m
      (164-fold) as compared to the long-distance run (3000-m). The alpha 1-m excretion
      rates were increased to a lesser extent by the exercises. The IAP activity was
      slightly increased (+90%) by the 400-m run while the TNAP and NAG activities
      showed a 6.8-fold and a 3.6-fold increase, respectively, after this event.
      Smaller increases were recorded for the long-distance run (P = 0.05). To
      conclude, the present investigation showed that: (1) post-exercise proteinuria is
      related to the absolute intensity of exercise; (2) the impairment of protein
      reabsorption is revealed better by changes in Alb and beta 2-m; (3) changes in
      TNAP and NAG activities could reveal biochemical modifications that occur in the
      proximal tubule, particularly at the S1-S2 segment.

PMID- 9243176
TI  - Exercise performance and magnetic resonance imaging-determined thigh muscle
      volume in children.
AB  - This study examined the relationships between thigh muscle volume (TMV) and
      aerobic and anaerobic performance in children. A total of 32 children, 16 boys
      and 16 girls, aged 9.9 (0.3) years completed a treadmill running test to
      exhaustion for the determination of peak oxygen uptake (peak VO2) and a Wingate
      Anaerobic Test (WAnT) for the determination of peak power (PP) and mean power
      (MP). The volume of the right thigh muscle was determined using magnetic
      resonance imaging. TMV was not significantly different in boys and girls [2.39
      (0.29) l vs 2.18 (0.38) l, P > 0.05]. Peak VO2 and MP were significantly higher
      in boys than girls (P < 0.01) whether expressed in absolute, mass-related or
      allometrically scaled terms. Absolute PP was not significantly different in boys
      and girls but mass-related and allometrically scaled values were higher in boys
      (P < 0.01). TMV was correlated with absolute peak VO2, PP and MP in both sexes (r
      = 0.52-0.89, P < 0.01). In boys, mass-related PP was correlated with TMV (r =
      0.53, P < 0.01), and in girls mass-related peak VO2 was correlated with TMV (r = 
      0.61, P < 0.01). However, in neither sex were allometrically scaled peak VO2, PP
      or MP correlated with TMV (P > 0.05). There were no significant differences
      between boys and girls in terms of peak VO2, PP or MP when expressed in a ratio
      to TMV or allometrically scaled TMV. In conclusion, this study has demonstrated
      that, when body size is appropriately accounted for using allometric scaling, TMV
      is unrelated to indices of aerobic and anaerobic power in 10-year-old children.
      Furthermore, there appear to be no qualitative differences in the muscle function
      of boys and girls in respect of aerobic and anaerobic function.

PMID- 9243177
TI  - Serum insulin-like growth factor I and physical performance in prepubertal
      Bolivian girls of a high and low socio-economic status.
AB  - The aim of the study was to determine if a decrease in serum insulin-like growth
      factor I (Igf-I) levels under marginal malnutrition is responsible for the lower
      physical performance of girls of a low socio-economic status (LSES). Girls were
      selected after physical examination (Tanner's stage 1) and anthropometric
      measurements (height, body mass or mb, body mass index or BMI = mb height2). Lean
      body mass mb,1 was measured after skinfold thickness determination; serum IGE-I,
      by radioimmunoassay; maximal O2 consumption, (VO2max), directly during
      incremental exercise up to exhaustion; and maximal aerobic power (Wmax), using
      the force-velocity test. LSES girls (n = 31) had been malnourished in the past
      and, currently, were suffering from marginal malnutrition: they were smaller
      (135.2 +/- 5.5 vs 146.1 +/- 4.3 cm), lighter (31.7 +/- 3.9 vs 37.6 +/- 5.0 kg),
      exhibited a lower mb,1 (24.2 +/- 2.5 vs 27.5 +/- 3.0 kg) but same BMI compared
      with HSES (high socio-economic status) girls (n = 32). Igf-I levels (27.7 +/- 7.9
      vs 34.1 +/- 6.5 nmol.1(-1), VO2max (45.26 +/- 4.72 vs 50.74 +/- 6.02 ml. min-1.kg
      1 LBM) and Wmax (6.00 +/- 1.15 vs 8.70 +/- 1.53 W.kg-1 mb,1 were lower in LSES
      girls. Moreover, the differences in every parameter were not the consequence of
      the younger age (10.8 +/- 0.9 vs 11.2 +/- 0.6 years) of the LSES girls. Our
      results provide evidence that the lower Wmax of undernourished prepubertal girls
      was partly the consequence of alterations in muscle function at the qualitative
      level, as a result of a decrease in Igf-I levels. Conversely, under normal
      nutritional conditions, anthropometric characteristics only are explicatory
      factors for physical performances.

PMID- 9243178
TI  - Substrate utilisation during exercise and shivering.
AB  - It is generally assumed that exercise and shivering are analogous processes with
      regard to substrate utilisation and that, as a consequence, exercise can be used
      as a model for shivering. In the present study, substrate utilisation during
      exercise and shivering at the same oxygen consumption (VO2) were compared.
      Following an overnight fast, eight male subjects undertook a 2-h immersion in
      cold water, designed to evoke three different intensities of shivering. At least
      1 week later they undertook a 2-h period of bicycle ergometry during which the
      exercise intensity was varied to match the VO2 recorded during shivering. During
      both activities hepatic glucose output (HGO), the rate of glucose utilisation
      (Rd), blood glucose, plasma insulin, free fatty acid (FFA) and beta
      hydroxybutyrate (B-HBA) concentrations were measured. The VO2 measured during the
      different levels of shivering averaged 0.49 l.min-1 (level 1: low), 0.6 l.min-1
      (level 2: low-moderate), and 0.9 l.min-1 (level 3: moderate), and corresponded
      closely to the levels measured during exercise. HGO and Rd were greater (P <
      0.05) during exercise than during shivering at the same VO2 (9.5% and 14.7%,
      respectively). The average (SD). HGO during level 3 exercise was 3.0 (0.91) mg.kg
      1.min-1 compared to 2.76 (1.0) mg.kg-1.min-1 during shivering. The values for Rd
      were 3.06 (0.98) mg.kg-1.min-1 during level 3 exercise and 2.68 (0.82) mg.kg
      1.min-1 during shivering. Blood glucose levels did not differ between conditions
      averaging 5.4 (0.3) mmol.l-1 over all levels of shivering and 5.2 (0.3) mmol.l-1
      during exercise. Plasma FFA and B-HBA were higher (P < 0.01) during shivering
      than during corresponding exercise (12.3% and 33.3%, respectively). FFA averaged
      0.61 (0.2) mmol.l-1 over all levels of shivering and 0.47 (0.16) mmol.l-1 during
      exercise. The figures for L-HBA were 0.44 (0.13) mmol. l-1 during all levels of
      shivering and 0.32 (0.1) mmol.l-1 during exercise. Plasma insulin was higher (P <
      0.05) during level 2 and 3 shivering compared to corresponding exercise; at these
      levels the average value for plasma insulin was 95.9 (21.9) pmol.l-1 during
      shivering and 80.6 (16.1) pmol.l-1 during exercise. On the basis of the present
      findings it is concluded that, with regard to substrate utilisation, shivering
      and exercise of up to 2 h duration should not be regarded as analogous processes.

PMID- 9243179
TI  - Apoptosis and carcinogenesis.
AB  - This article attempts to summarize the rapidly advancing field of apoptosis and
      its regulation, with particular reference to cancer. The long-recognized
      stereotyped morphology of apoptosis is seen to be the result of convergence of
      biochemical pathways on common effector mechanisms in which a major element is
      activation of cysteine proteases with a preference for cleavage at aspartate
      residues (caspases). The substrates of this reaction are widely dispersed in the
      nucleus, cytoplasm and cytoskeleton. Caspase activation is the end result of
      protean stimuli, physiological and pathological. Pathological stimuli include
      damage to cell membranes, mitochondrial function, DNA and possibly other critical
      intracellular organelles. Several, distinct agents are known that may be part of
      the signaling pathways that couple injury to these cellular components to
      apoptosis: ceramide, collapse of mitochondrial transmembrane potential, p53
      activation. Other stimuli are signaled through cytokine receptors (such as
      fas/APO-1/CD 95 and TNFRI and II) or transcription factors (such as p53, IRF-1
      and rb). The transduction of these stimuli into caspase activation is regulated
      by a large family of proteins (the bcl-2 family). Cancer and apoptosis are
      related in many ways. In particular, this article explores the possibility that
      defective apoptosis may permit the persistence of damaged, mutated cells that
      would otherwise have been deleted. The conditions that lead to this scenario
      appear to be tissue-specific.

PMID- 9243180
TI  - Phylogenetic analysis of membrane trafficking proteins: a family reunion and
      secondary structure predictions.
AB  - The realization that a highly conserved family of membrane proteins are localized
      to transport vesicles and selectively interact with proteins anchored at
      appropriate target sites of membrane fusion inspired a simple and compelling
      explanation of how proteins might be transferred and segregated within the cell,
      the "SNARE hypothesis". This model holds that vesicle and target membrane
      proteins (designated as v-SNARE and t-SNARE proteins, respectively) wind around
      one another to form a three-stranded coiled coil structure, termed the prefusion
      complex. While the molecular topology of the prefusion complex has not been
      established, the concept that phylogenetically diverse SNARE proteins may become
      interlocked in a stable coiled coil is particularly attractive, because such a
      tertiary fold would only be permitted between strictly matched binding partners.
      For this reason, we have performed a phenetic analysis of all known SNARE
      sequences to assess the evolutionary and structural relatedness of these ancient
      protein families. Our phylogenetic analysis and consensus structure predictions
      revealed that syntaxin and SNAP-25 homologs are significantly related and
      constitute a superfamily of t-SNARE proteins that fall naturally into four major
      classes with distinct architectural motifs. The synaptobrevins sorted into three
      different classes of v-SNARE proteins. Comparison of the consensus structure
      predictions within each lineage or class of SNARE proteins strongly implied that
      coiled coil domains may not be required for fusion complex assembly in simple
      eukaryotic cells. It is our hypothesis that SNARE proteins in the late secretory
      pathway of mammalian cells may have elaborated more complex secondary structures
      (coiled coils), at about the time metazoan organisms diverged from yeast, that
      provide a sterically rigid foundation for positioning a conserved binding domain,
      the amphipathic alpha-helix.

PMID- 9243181
TI  - A novel pancreas-specific serpin (ZG-46p) localizes to the soluble and membrane
      fraction of the Golgi complex and the zymogen granules of acinar cells.
AB  - By immunoscreening a cDNA expression library of rat pancreas using a polyspecific
      antiserum raised against purified pancreatic zymogen granule membranes, we have
      identified a cDNA clone coding for a novel protein, named ZG-46p. The cDNA
      contains an ORF of 1215 bp coding for a protein of 405 amino acids with a
      calculated molecular mass of 46 kDa. Sequence analysis revealed high homologies
      to known serine protease inhibitors (serpins), e.g. human anti-thrombin III
      (47.2%) or human and rat anti-trypsin (44%). The highest homology is present in
      the serpin signature, a consensus sequence common to all serpins, as well as its
      flanking hinge region. Northern blot analysis reveals the exclusive expression of
      the novel serpin mRNA in the pancreas, both during embryonic development and in
      the adult gland but not in the acinar carcinoma cell line AR4-2J. In vitro
      translation experiments demonstrate that the protein is N-glycosylated, but in
      vivo and in vitro phosphorylation was not found in spite of multiple
      phosphorylation sites. By immunofluorescence studies pancreatic serpin was
      localized predominantly to the Golgi complex in a similar distribution as the
      marker protein TGN38. Western blot analysis of various subcellular fractions
      showed ZG-46p mainly as soluble protein in the Golgi but also in zymogen granule
      content. A minor but significant portion of the protein was firmly attached to
      both the zymogen granule and Golgi membranes as Triton X-114 extraction
      indicates. The cellular localization, the distribution in the soluble and
      membrane fraction of Golgi complex and zymogen granules, and the finding that
      pancreatic serpin is associated with aggregated secretory proteins suggest a role
      in the sorting of pancreatic enzymes during granule formation.

PMID- 9243182
TI  - Localization of the FA-CHIP water channel in frog urinary bladder.
AB  - Like mammalian kidney collecting duct, the water permeability of frog urinary
      bladder epithelial cells is antidiuretic hormone (ADH)-sensitive. In kidney, this
      permeability is mediated by water channels named aquaporins. We recently reported
      the cloning of the frog aquaporin CHIP (FA-CHIP), a water channel from frog
      urinary bladder. FA-CHIP has 79% identity with rat Aquaporin 1 (AQP1) and only
      42% identity with the kidney collecting duct Aquaporin 2 (AQP2). The purpose of
      this study was to examine the localization of FA-CHIP in frog urinary bladder. We
      raised antibodies against peptides of 15 to 17 residues, encompassing the N-ter
      and C-ter regions of FA-CHIP. Anti-FA-CHIP antibodies were used for Western
      blotting, indirect immunofluorescence microscopy and gold labeling electron
      microscopy in urinary bladder and other frog tissues. By Western blotting of frog
      urinary bladder total homogenate, the antibodies recognized a band of 29 kDa and
      glycosylated forms of the protein between 40 and 70 kDa. No signal was found on
      membrane preparations from epithelial cell homogenate. FA-CHIP was also found in
      frog skin, brain, gall bladder, and lung. In immunofluorescence microscopy on
      urinary bladder sections, FA-CHIP was localized to endothelial cells of blood
      capillaries and on mesothelial cells of the serosal face. Red blood cells,
      epithelial and basal cells were unstained. The localization of FA-CHIP in cell
      plasma membranes was confirmed by gold labeling electron microscopy. In other
      positive tissues, FA-CHIP was also localized to capillaries. In brain, plasma
      membranes of epithelial cells were also stained. In conclusion, like its
      mammalian homologue AQP1, FA-CHIP appears to be localized to constitutively water
      permeable cells of frog. Therefore, it belongs to the AQP1 family of proteins
      although unlike AQP1, FA-CHIP is absent from red blood cells and kidney. In frog
      urinary bladder and skin, FA-CHIP probably plays an important role in water
      transport across the barriers in series with the ADH-sensitive epithelial cells.

PMID- 9243183
TI  - Mammalian occludin in epithelial cells: its expression and subcellular
      distribution.
AB  - Occludin has been identified from chick liver as a novel integral membrane
      protein localizing at tight junctions, and the cDNA encoding its mammalian
      homologue was identified very recently (Ando-Akatsuka, Y., M. Saitou, T. Hirase,
      M. Kishi, A. Sakakibara, M. Itoh, S. Yonemura, M. Furuse, Sh. Tsukita, J. Cell
      Biol. 133, 43-47 (1996)). Here we describe the basic properties of mammalian
      occludin in epithelial cells at the DNA, RNA, and protein levels. The human
      occludin gene was mapped to chromosome band 5q13.1 by fluorescent in situ
      hybridization. Northern blotting identified several occludin mRNA bands,
      suggesting the possible expression of several alternatively spliced products.
      Occludin mRNA was detected in cultured epithelial cells, but not in cultured
      fibroblasts. The mRNA level was high in the testis, kidney, liver, lung, and
      brain, which reportedly bear well-developed tight junctions. We then produced
      monoclonal and polyclonal antibodies using recombinant mouse occludin as the
      antigen, which reacted not only with mouse, but also human, dog and pig occludin.
      These antibodies recognized several bands around 60 kDa in epithelial cells but
      not in fibroblasts. Immunofluorescence microscopy of various tissues revealed
      that the staining intensity of occludin correlated well with the number of tight
      junction strands in epithelial cells. By contrast, the staining of ZO-1, a well
      characterized tight junction-associated protein, was not specific for tight
      junctions. Furthermore, the exclusive concentration of occludin at tight
      junctions in epithelial cells was confirmed by immunoreplica electron microscopy.

PMID- 9243184
TI  - Decrease of bradykinin-induced glomerular contraction in diabetic rat: a new
      cellular interpretation.
AB  - The contractile response to bradykinin (BK), measured by the reduction of the
      planar surface area, was studied in glomeruli and mesangial cells (MC) isolated
      from diabetic rats (D) one week after diabetes induction with injection of
      streptozotocin (STZ; 60 mg kg-1, i.p.). Results were compared with age and weight
      matched untreated rats (N) and were expressed by two parameters of cell activity,
      the mean maximum contraction (MMC) and the proportion of contractile cells (PCC).
      Glomerular and mesangial contraction were found to be clearly reduced in diabetic
      rats in response to 100 nM BK. The lower contractile response was associated with
      a decrease of both glomerular calcium uptake and mesangial cell intracellular
      calcium mobilization. The fact that cell pretreatment with two protein kinase C
      (PKC) inhibitors, phorbol 12-13 myristate acetate and calphostin, lowered normal
      cell contraction at the level of that found in diabetic MC without any
      significant effect in the latter, suggests the involvement of a PKC pathway,
      perhaps by a decrease of activatable PKC in diabetes. In addition, our results
      led to the first description of a possible role of the kallikrein-kinin system in
      the early glomerular hemodynamic changes occurring in diabetes. Insulin (1-200
      nM) increased the contractile response of cultured diabetic cells (MMC), and in
      this case, it also increased the PCC. It must be stressed that the effect of 1 nM
      insulin on the former (88% increase) was very much smaller than its effect on the
      latter (103% increase). The combination of the two parameters (contraction index,
      CI) provided a realistic evaluation of the contractile capacities of the cell
      population of the cultures as a whole. The differences in this index between
      normal and diabetic cell populations, in the absence or presence of insulin, were
      strictly parallel to those found in intact glomeruli. Finally, our results
      further confirm (Ouardani et al., Biol. Cell 86, 127, (1996)) the limit of the
      first five cell passages within which cultured MC can be reasonably used for the
      study of contractile abnormalities occurring in the early steps of diabetic
      state.

PMID- 9243185
TI  - Conservation of mitochondrial targeting sequence function in mitochondrial and
      hydrogenosomal proteins from the early-branching eukaryotes Crithidia,
      Trypanosoma and Trichomonas.
AB  - Kinetoplastid protozoa are the earliest-branching eukaryotes to possess a true
      mitochondrion. This organelle is host to a variety of intriguing and unique
      features, including RNA editing. We examined the characteristics of protein
      import into mitochondria of Trypanosoma brucei. Dihydrofolate reductase (DHFR)
      carrying a yeast mitochondrial targeting signal was correctly translocated into
      trypanosome mitochondria in vivo, as were DHFR fusion proteins bearing two
      unusually short (7-9 amino acids) presequences from trypanosomatids. The short
      trypanosomal targeting signals were functional in Saccharomyces cerevisiae as
      well, but their targeting efficiency was lower and processing was absent.
      Trichomonads branched even earlier than kinetoplastids in eukaryotic evolution
      and contain energy-generating organelles called hydrogenosomes. The origin of
      hydrogenosomes has been controversial, but most evidence suggests that they are
      related to mitochondria. Putative hydrogenosomal targeting signals from
      Trichomonas vaginalis are short (5-12 amino acids). Three such sequences were
      capable of targeting a passenger protein to mitochondria both in yeast and in
      trypanosomes, and one of the hydrogenosomal presequences was efficiently
      processed in both organisms. These findings suggest a resemblance between the
      import machineries of mitochondria and hydrogenosomes.

PMID- 9243186
TI  - DNA gyrase involvement in chloroplast-nucleoid division in Cyanidioschyzon
      merolae.
AB  - Cyanidioschyzon merolae is a unicellular alga with one chloroplast and one
      mitochondrion per cell. Each of these organelles has a simple nucleoid located in
      the central area. Prior to mitosis and cytokinesis, both the division of
      organelle nucleoids and organellokinesis occur simultaneously. We investigated
      the effects of nalidixic acid, an inhibitor of DNA gyrase, on the replication and
      division of organelle nucleoids. Using microfluorometry, we monitored the
      synthesis of organelle DNA (organelle S phase) in synchronous cultures. In both
      the chloroplast and the mitochondrion, DNA synthesis occurred from the start of
      the light period and ceased within 3 h. The addition of nalidixic acid at the
      start of the light period inhibited DNA synthesis in both organelles. Next, we
      added nalidixic acid to the synchronous culture at the beginning (just before the
      organelle S phase) or at the end (organelle G2 phase) of the light period and
      monitored the division of organelle nucleoids in the dark period. Approximately
      50 to 70% of chloroplast nucleoids divided unequally in both experiments. Despite
      the unequal division of the chloroplast nucleoids, electron microscopy revealed
      that the chloroplasts were divided into equal daughter chloroplasts by the
      chloroplast-divided ring. During the same treatments, all of the mitochondrial
      nucleoids underwent normal and equal division. Our results suggest the
      involvement of DNA gyrase in the replication of chloroplast and mitochondrial DNA
      and in the division of the chloroplast nucleoid, as well as a difference in
      mechanism between the division of chloroplast and mitochondrial nucleoids.

PMID- 9243187
TI  - Preassembly of annulate lamellae in egg extracts inhibits nuclear pore complex
      formation, but not nuclear membrane assembly.
AB  - Annulate lamellae (AL) are cytoplasmic structures containing pore complexes
      similar in composition and morphology to nuclear envelope pore complexes. We have
      tested the ability of Xenopus egg extract to support nuclear membrane and pore
      complex formation when chromatin is added to extract only after annulate lamellae
      had been allowed to assemble (preincubated extract). We have observed that
      preassembly of AL does not inhibit the formation of a double membrane surrounding
      sperm chromatin. However, these double membranes are often distended, do not
      support accumulation of karyophilic proteins, and do not possess immunologically
      or morphologically identifiable pore complexes. We have demonstrated that nuclear
      pore complex assembly and function can be rescued by adding isolated egg vesicles
      to the preincubated extract. Our data support the conclusion that multiple
      vesicle populations are utilized in the formation of a nuclear envelope,
      including: vesicle population(s) which are common to pore formation in nuclear
      envelopes and annulate lamellae, and vesicle population(s) which seem to be
      preferentially utilized for nuclear membrane assembly.

PMID- 9243188
TI  - Expression of PSA-N-CAM in human neuroblastoma cells induced to neuronal
      differentiation by retinoic acid.
AB  - The neural cell adhesion molecule (N-CAM) plays a significant role in the
      development of the nervous system. Three different isoforms of the molecule have
      been described, with molecular masses of 180, 140 and 120 kDa, whose differential
      expression in neurons seems to be related to their state of differentiation. We
      took advantage of the use of the human neuroblastoma cell line LAN-5, which can
      be differentiated in vitro by retinoic acid (RA) into neuronal cells, for
      studying the expression of N-CAM isoforms, and their polysialic acid (PSA)
      content, at the protein and mRNA levels. Anti-N-CAM polyclonal antibodies
      recognizing all the N-CAM isoforms and a monoclonal antibody recognizing PSA were
      used in Western blot experiments with extracts from undifferentiated and RA
      differentiated cells. We found that undifferentiated cells express very little of
      the 180 kDa N-CAM isoform and a large amount of the 140 kDa isoform. A 4-fold
      increase in the expression of the 180 kDa N-CAM isoform was obtained when LAN-5
      cells were differentiated by RA for 8 days, whereas a 1.8-fold increase in the
      expression of the 140 kDa N-CAM isoform was observed upon differentiation.
      Similarly, the levels of the 7.4 kb mRNA coding for N-CAM 180 kDa, determined by
      Northern blot analysis, were barely detectable in undifferentiated cells, and
      showed a 3.8-fold increase upon differentiation. By contrast, only a 1.3-fold
      increase in the 6.7 kb mRNA, coding for the 140 kDa N-CAM isoform, was observed.
      N-CAM was always found in its polysialylated form in both undifferentiated and RA
      differentiated cells. This indicates that, in LAN-5 cells, the expression and
      activity of the polysialytransferase enzyme precedes the acquisition of a
      neuronal phenotype.

PMID- 9243189
TI  - Nebulin-like protein in the earthworm Eisenia foetida. Immunocytochemical
      electron microscopic study and western blot analysis of several muscle cell
      types.
AB  - Nebulin is a giant protein (500-900 kDa), which has been reported only in the
      skeletal muscle (not in cardiac muscle) of vertebrates. The possible presence and
      distribution of nebulin-like proteins in obliquely striated muscles (body wall
      and inner muscular layer of the pseudoheart) and smooth muscle (outer muscular
      layer of the pseudoheart) from the earthworm Eisenia foetida have been examined
      by means of Western blotting analysis and immunoelectron microscopy, using
      antibodies against mouse nebulin. The results were compared with those obtained
      in skeletal, cardiac and smooth muscles of the mouse. In the mouse,
      immunoreaction to nebulin was observed only in the skeletal muscle and extended
      along the length of the thin filament. In the earthworm, immunoreaction to a
      nebulin-like protein was found in the muscle of the body wall and the inner
      muscular layer of the pseudoheart, but not in the outer muscular layer of the
      pseudoheart. By electron microscopy, immunolabeling to this protein was observed
      along the whole length of the thin filament. Western blotting analysis of this
      nebulin-like protein showed a single band at an estimated molecular mass between
      350 and 450 kDa that is slightly lower than that of mouse skeletal muscle
      nebulin.

PMID- 9243190
TI  - Colocalization of stomatin (band 7.2b) and actin microfilaments in UAC epithelial
      cells.
AB  - Cytolocalization of stomatin, an integral membrane protein also called
      erythrocyte band 7.2b, was investigated in a human epithelial cell line in which
      the expression of this protein is up-regulated after treatment with interleukin-6
      and dexamethasone. A monoclonal antibody against stomatin was used to perform
      immunofluorescence and immunoelectron microscopy. The data show that stomatin
      concentrates preferentially in small plasma membrane protrusions. It is also
      found in abundance in a juxtanuclear structure possibly derived from the Golgi
      apparatus. Fluorescent double staining using the anti-stomatin antibody and the
      actin binding drug phalloidin shows a significant degree of colocalization of
      stomatin and cortical actin microfilaments. This association remains after actin
      filament disruption disruption by cytochalasin D treatment indicating a strong
      connection between stomatin and the membrane-associated cytoskeleton.

PMID- 9243191
TI  - Maternal consequences of caesarean section. A retrospective study of intra
      operative and postoperative maternal complications of caesarean section during a
      10-year period.
AB  - OBJECTIVES: This study was performed to assess the intra-operative surgical
      complications and postoperative maternal morbidity rate of caesarean section.
      STUDY DESIGN: A total of 2647 women, delivered by caesarean section in our
      department between 1983 and 1992, were studied retrospectively. Three caesarean
      section groups were formed: (1) primary elective, (2) primary acute, without any
      effort to deliver vaginally, and (3) secondary acute, due to a failed vaginal
      delivery. The Student's-t-, Fisher-exact- and chi 2-test were used for
      statistical analysis. RESULTS: The overall maternal intra-operative complication
      rate was 14.8%. The most common complications were lacerations of the uterine
      corpus (10.1%) and bloodloss > or = 1000 ml (7.3%). The complication rate of the
      secondary group (23.4%) was significantly higher (p < 0.001) compared to both
      primary groups (7.4%). The overall maternal postoperative morbidity rate was
      35.7%. Fever (24.6%), bloodloss between 1000 and 1500 ml (4%), haematoma (3.5%)
      and urinary tract infections (3.0%) were the most frequent complications. The
      primary elective group showed significantly (p < 0.001) lower major (2.6%) and
      minor (23.7%) complication rates compared to the emergency groups (major 5.2%,
      minor 34%). CONCLUSION: Emergency caesarean sections carried the greatest risks
      regarding maternal complications compared to elective procedures.

PMID- 9243192
TI  - The role of transvaginal sonography in predicting recurrent preterm labour in
      patients with intact membranes.
AB  - Our purpose was to determine whether funnelling of the cervical internal os,
      length of the endocervical canal, cervical index, funnel length and funnel width
      determined by transvaginal sonography are predictive of recurrent preterm labour.
      Of 112 women, 65 admitted to the hospital for preterm labour with intact
      membranes had transvaginal sonographic evaluation of the cervix before digital
      cervical examination and institution of tocolysis. The following measurements
      were obtained: (1) presence of funnelling, (2) endocervical canal length, (3)
      cervical index, (4) funnel length and (5) funnel width. Logistic regression
      analysis was performed to determine the variables that made a significant
      contribution to the prediction of recurrent preterm labour. A total of 65
      eligible women completed the study. Recurrent preterm labour was significantly
      associated with the presence of funnelling (85.2% vs. 23.3%) and short
      endocervical canal length, large cervical index and long funnel length as noted
      on transvaginal cervical sonography. The presence of funnelling, shorter
      endocervical canal length, larger cervical index and longer funnel length were
      suggestive of true preterm labour and its recurrence. Transvaginal sonographic
      examination of the uterine cervix is a useful procedure to predict recurrent
      preterm labour with intact membranes.

PMID- 9243193
TI  - Prawn sandwiches, red herrings and abdominal pregnancy.
AB  - An unusual presentation of abdominal pregnancy is reported. The difficulty in
      diagnosis of this form of ectopic pregnancy, and the potential risks of delayed
      intervention are highlighted. The association with uterine anomaly, in this case
      uterus didelphys, is discussed.

PMID- 9243194
TI  - Use of a DNA typing method to investigate a fatal perinatal infection due to
      Staphylococcus aureus.
AB  - The aim of this study was to determine, by random amplified polymorphic DNA
      analysis, the origin of a fatal Staphylococcus aureus perinatal infection which
      occurred after multiple cervical examinations before induction of labor for
      patient convenience. This DNA typing method was able to demonstrate that this
      infection originated from S. aureus genital carriage and urinary tract infection
      of the mother, and was not acquired in the hospital. This observation argues for
      the systematic screening of genital flora for highly virulent strains before
      induction of labor for non medical reasons. In addition, the DNA typing method
      used demonstrates that one neonate was subsequently infected by the strain
      responsible for the chorioamnionitis. This shows that molecular typing methods
      can help determine hospital staff responsibility.

PMID- 9243195
TI  - Circulating levels of relaxin are normal in pregnant women with pelvic pain.
AB  - OBJECTIVE: The hormone relaxin induces loosening of the pelvic ligaments and
      joints in several species. Previous studies have suggested a similar role for
      relaxin during human pregnancy. Furthermore, a correlation has been noted between
      high circulating levels of this hormone and severe pelvic pain in pregnant women.
      The present study was designed to evaluate whether serum relaxin concentrations
      were elevated in pregnant women with clear subjective and objective evidence of
      pain attributable to relaxation of the pelvic ligaments. STUDY DESIGN: Serum
      relaxin was measured at week 33 of gestation in 455 pregnant women with clearly
      defined pain in their pelvic joints and 455 normal pregnant controls matched for
      age and parity. All participants underwent an examination consisting of a
      structured questionnaire and fifteen specific tests for pelvic joint pain. The
      group with pain was further subdivided into four subgroups with different levels
      of disability and prognosis. Relaxin concentrations were measured using enzyme
      linked immunoassay. RESULTS: There was no difference in serum relaxin
      concentration between the control and study group, nor between the subgroups of
      women with pelvic pain. CONCLUSION: We failed to confirm an earlier claim that
      circulating relaxin levels are related to pelvic girdle pain in pregnant women.

PMID- 9243196
TI  - A benign polypoid adenomyoma: an unusual cause of persistent fetal transverse
      lie.
AB  - Persistent fetal transverse lie at term is uncommon. A case of benign polypoid
      adenomyoma, found during Caesarean section, as a cause of abnormal lie in a
      primigravida is reported. A clear distinction as shown can be drawn between
      breech presentation and transverse lie at term, and between transverse lie in
      multiparous and nulliparous women. Prophylactic external version was not
      performed in this case and the reasons are discussed. Careful search for the
      cause of transverse lie especially in a primigravida is recommended.

PMID- 9243197
TI  - Interleukin-6 and neopterin levels in serum of patients with preterm labour with
      and without infection.
AB  - We estimated the levels of interleukin 6 (IL-6) and neopterin, in serum of twelve
      nonpregnant (group A) and 28 pregnant women between 28-36 weeks of pregnancy.
      Group B consisted of eight patients with uncomplicated pregnancy, group C
      consisted of thirteen pregnant women with clinical signs of preterm labour and
      without laboratory markers of infection and group D consisted of seven pregnant
      women with signs of preterm labour and with laboratory markers of infection. The
      levels of IL-6 and neopterin were significantly higher in group D compared to
      groups A, B and C (p < 0.05). Similarly, the level of C-reactive protein (CRP)
      and total white blood cell count (the laboratory markers of infection) were
      significantly higher in group D than in groups A, B and C. Total white blood cell
      count was significantly lower in group A than in group B and D (p < 0.05). There
      were no significant differences in values of IL-6, neopterin and CRP between
      groups A, B and C (p > 0.05). In all groups, significant correlations were found
      between IL-6 and neopterin as well as total white blood cell count and CRP. Our
      results suggest that IL-6 and neopterin may be the markers of preterm labour
      caused by infection. On the other hand, cell-mediated immune response may be
      involved in the mechanisms of preterm labour.

PMID- 9243198
TI  - Psychosocial profile of women seeking breast reconstruction.
AB  - As opposed to studies focused on the role of reconstruction in the rehabilitation
      of cancer patients, the aim of this study is to define what kind of women undergo
      post-mastectomy reconstruction. The social, cultural and psychological variables
      influencing women in this choice were assessed using a questionnaire administered
      to 45 women who had breast reconstruction and 51 who did not. An univariate
      analysis shows significant differences between the two groups regarding age,
      education, socioeconomic status, leisure activities, sexual intercourse,
      information about breast reconstruction and fear of recurrence. These results
      show that social status is a deciding factor in a woman's access to information
      about reconstruction. If every women undergoing mastectomy is to be given the
      opportunity of plastic surgery, we think that information must be adapted to
      psychosocial profile.

PMID- 9243199
TI  - A review of trophoblastic diseases at the medical school of Dicle University.
AB  - Gestational trophoblastic disease cases encountered in 88 pregnant women during a
      period between January 1985 and June 1992 were retrospectively studied. During
      the same period we had 6800 deliveries. The incidence of gestational
      trophoblastic diseases was 12.9 per 1000 deliveries. Of these cases 72 (81.8%)
      were diagnosed as hydatidiform mole and 16 (18.2%) were diagnosed as
      choriocarcinoma in histopathological investigations. The preferred method of
      treatment for cases of hydatidiform mole was termination with suction curettage
      and oxytocin perfusion. Trophoblastic diseases were common in women with five or
      more pregnancies from rural areas and our incidence was higher when compared with
      similar studies. Moreover, our patients had low socio-economic and poor
      educational status. All these factors seem to be etiologic reasons, besides
      multiparity.

PMID- 9243200
TI  - Abdominal wall metastases after surgical resection of an immature teratoma of the
      ovary.
AB  - In this case report the diagnostic process is discussed leading to a rather late
      correct diagnosis of immature teratoma. The authors advice preoperative
      determination of alpha-fetoprotein in all women with ovarian tumours under 40
      years of age. The limitations for pathologists to assess immaturity within a
      teratoma are stressed.

PMID- 9243201
TI  - Aggressive endometrial cancer in a young patient.
AB  - An unusually aggressive case of endometrial cancer in a 30 year old woman is
      presented. The patient experienced abnormal uterine bleeding, at times requiring
      blood transfusions, for almost half a year before the diagnosis was revealed. For
      obvious reasons there is a reluctancy to perform invasive examinations in young
      women. The diagnostic options are discussed.

PMID- 9243202
TI  - Indications of laparoscopic hysterectomy.
AB  - OBJECTIVE: To determine when vaginal hysterectomy is contra-indicated and
      abdominal hysterectomy should be performed. To assess when laparoscopic surgery
      can avoid the abdominal procedure, and to determine the indications of this new
      technique in case of benign uterine lesions without prolapse. MATERIALS AND
      METHODS: A retrospective study of 171 hysterectomies performed by the same
      surgeon for benign uterine lesions without prolapse. When possible the vaginal
      route was chosen and the following criteria were studied: indication for
      hysterectomy, previous surgery, uterine weight, duration of the procedure, intra-
      and post-operative bleeding, complications and recovery time. Statistical
      analysis was performed using the Chi2 test and the Fisher's exact test when
      appropriate with a level of significance of p < 0.05. RESULTS: One hundred and
      nine vaginal (60.4%) and 62 abdominal (39.6%) hysterectomies were performed and
      the main indication was menometrorrhagia (respectively 97 (89%) and 49 (79%)
      cases). The indication for abdominal surgery was an enlarged uterus in 47
      patients (76%). In 10 cases (6%) laparoscopy was indicated because of severe
      endometriosis, previous abdominal surgery or a suspect adnexal cyst. No
      complications occurred in either group. The duration of the procedure, blood loss
      and recovery time were lower in the vaginal group (p < 0.05). COMMENTS: Uterine
      volume limits vaginal hysterectomy, and this cannot be overcome by laparoscopic
      surgery. Only severe adhesions and endometriosis are more amenable to
      laparoscopic hysterectomy. The laparoscopic hysterectomy rate should not
      reasonably exceed 10 to 15%, yet is as high as 63% in some studies. Further
      studies are needed to determine the value of laparoscopic hysterectomy relative
      to the vaginal route.

PMID- 9243203
TI  - Percutaneous needle colposuspension to Cooper's ligament for the treatment of
      stress incontinence in women: a report of 82 cases.
AB  - We describe a procedure for the treatment of genuine stress urinary incontinence
      by percutaneous needle colposuspension of the bladder neck to Cooper's ligament.
      The procedure was performed in 82 patients and was associated with other
      procedures in 75 cases (91.5%). The mean operative time was 19 min (range 15 to
      30). One peroperative hemorrhagic complication (1.2%) was noted. Nine
      postoperative complications were observed (10.9%) including seven urinary
      infections, one retropubic hematoma and one fever of unknown etiology. The mean
      follow-up was 13 months (range 6 to 22). Eight patients had a failure of the
      technique. All failures were diagnosed during the two first postoperative months.
      They included five cases of detrusor instability and three of persistent urinary
      incontinence. No additional failure was noted among the 53 patients having a
      follow-up greater than 12 months, suggesting a good stability of this new
      technique of colposuspension with a success rate of 85%.

PMID- 9243204
TI  - The relationship between laparoscopic disease, pelvic pain and infertility; an
      unbiased assessment.
AB  - OBJECTIVES: To measure the relationship between laparoscopically detected pelvic
      pathology and pelvic pain or infertility. METHODS: Women undergoing diagnostic
      laparoscopy either for the investigation of pelvic pain, for sterilisation or for
      the investigation of infertility were studied. The indication for surgery was
      recorded before laparoscopy. At operation a series of 35-mm slide photographs
      were taken of the pelvis and later scored by two independent assessors without
      knowledge of the indication for surgery. RESULTS: Satisfactory photographs were
      obtained in 298 women. Minimal endometriosis was not associated with pain
      (adjusted OR 1.3; 0.5-2.8), although moderate disease was non-significantly so
      (2.5; 0.4-7.1). Severe disease was significantly more common and never occurred
      in patients being sterilised (P = 0.02). The odds of pain were not increased in
      the presence of dilated veins > 9 mm diameter (OR 1.1; 0.4-3.2) or adhesions (OR
      0.6; 0.2-4.7). The odds of infertility were non-significantly increased in the
      presence of minimal and moderate endometriosis (OR 2.0; 0.8-5.3, and OR 4.2; 0.6
      25 respectively) and again significantly more common in the presence of advanced
      disease (P = 0.002). The odds of infertility tended to be lower in the presence
      of severely dilated veins (OR 0.2; 0.032-1.2). There was no clear effect of
      adhesions (OR 0.9; 0.1-5.9). CONCLUSIONS: The long established associations
      between severe endometriosis and pelvic pain, and between endometriosis in
      general and infertility are confirmed. However there is little or no association
      between minimal endometriosis, pelvic adhesions or dilated pelvic veins and pain.
      Previously reported associations may have been an artefact of the surgeon's
      knowledge of the indication for operation when assessing the pelvis.

PMID- 9243205
TI  - Mothers and daughters menopausal ages: is there a link?
AB  - OBJECTIVE: To confirm whether there is a familial association in menopausal age
      between mothers and daughters. DESIGN: questionnaire survey of women attending an
      osteoporosis screening programme. SUBJECTS: 551 women who fulfilled the study
      inclusion criteria out of a random population sample of 2399 women aged between
      45 to 54 living within 32 km of Aberdeen who were selected from the community
      health index. RESULTS: 1758 women attended screening and completed the
      questionnaire. Of these only 1081 women were eligible being neither hormone
      replacement therapy users, nor had they had a hysterectomy. However, only 551
      (51%) knew their mothers menopausal age. Women with premature (< 40 years) and
      early menopause (< 45 years) reported significantly lower maternal menopausal
      ages than women with normal menopausal ages (43.81, 45.40 and 48.38 for
      premature, early and normal women respectively p < 0.0001). The odds of a woman
      having an early or premature menopause if their mother had experienced an early
      menopause was 6.02 (95% confidence interval 3.39 to 10.66). CONCLUSION: There
      seems to be a strong relationship between mothers and daughters menopausal age.

PMID- 9243206
TI  - Hormone replacement and the menopause: a European position paper. Writing Group
      on Women's Health of the Fondazione Giovanni Lorenzini Medical Science
      Foundation.

PMID- 9243208
TI  - Morphologic and morphometric aspects of the endometrium of postmenopausal women
      before and after cyclic oestrogen replacement treatment.
AB  - OBJECTIVE: The aim of the study is to observe the morphology and morphometry of
      the endometrium of postmenopausal women treated with cyclic conjugated
      oestrogens. STUDY DESIGN: Three groups of nine postmenopausal women received
      cyclic conjugated oestrogens for 21 days (with a seven-day pause) during six
      months. The endometrial specimens were obtained using a modified Novak suction
      curet, in the second or third day of the period of drug washout. The slides were
      stained with haematoxylin and eosin (H.E.) in order to measure epithelial height
      and determine the gland/stroma ratio. RESULTS: Morphologic examination showed
      that single daily doses of 0.3 mg of conjugated oestrogens caused discrete
      endometrial proliferation after three and six months of treatment. However, a
      more intense effect was observed in women receiving doses of 0.625 and 1.25
      mg/day of the hormone, in the same period. Morphometric study revealed
      significant increases both in epithelial thickness and in the gland-stroma ratio,
      specially in women receiving higher doses of the conjugated oestrogen (0.625 and
      1.25 mg/day). CONCLUSIONS: We concluded that there were marked proliferative
      alterations without atypias in the endometrium of women that received 0.625 and
      1.25 mg of conjugated oestrogens during six months.

PMID- 9243207
TI  - Frequent expression of Fas in gonadotropin-releasing hormone receptor-bearing
      tumors.
AB  - OBJECTIVE: Fas, a cell surface receptor, mediates cell death by means of
      apoptosis in a variety of cell types. Gonadotropin-releasing hormone (GnRH)
      receptor-bearing tumors undergo the apoptosis with GnRH analogs. The authors
      attempted to determine the frequency with which Fas is present in the GnRH
      receptor-bearing tumors. STUDY DESIGN: Surgically removed gynecological tumors
      were screened for GnRH receptor expression prior to analyses. Fas was
      characterized by immunoblotting of membrane proteins with the specific
      antibodies. Fas messenger ribonucleic acid (mRNA) was determined by reverse
      transcription-polymerase chain reaction using oligonucleotide primers synthesized
      according to the published Fas sequence. RESULTS: Immunoreactive Fas and Fas mRNA
      were detected in a high proportion (94.4%) of the specimens from endometrial
      carcinomas (8 of 9), ovarian carcinomas (7 of 7), and uterine leiomyosarcomas (2
      of 2); all these expressed GnRH receptor. There was neither substantial Fas nor
      GnRH receptor in 9 cervical carcinomas. Cloned cell lines gave identical results
      to those obtained in their respective mother tumors. CONCLUSION: These data might
      suggest the frequent expression of Fas in the GnRH receptor-bearing tumors, but
      not in the GnRH receptor-negative tumors. Despite a poorly understood processes
      of apoptosis at present, there may be at least some similarity in signal
      transduction pathway utilized by GnRH analogs and Fas ligands.

PMID- 9243209
TI  - Long gonadotrophin releasing hormone agonist/human menopausal gonadotrophin
      protocol for ovarian stimulation in intrauterine insemination treatment.
AB  - OBJECTIVE: This prospective study was undertaken to examine the usefulness of a
      long gonadotrophin releasing hormone agonist (GnRH-a)/human menopausal
      gonadotrophin (hMG) protocol in intrauterine insemination (IUI) treatment. The
      results were compared to those of clomiphene citrate (CC)/hMG/IUI. STUDY DESIGN:
      Seventy-five patients were recruited to a GnRH-a/hMG group (group 1) while 88
      patients underwent CC/hMG stimulation and served as controls (group 2). The study
      subjects were stimulated with a long GnRH-a/hMG regimen. IUI was performed 36 h
      after the administration of human chorionic gonadotrophin. RESULTS: The number of
      preovulatory follicles, the thickness of endometrium and sperm parameters were
      similar in both groups. The hMG requirements were significantly higher in group 1
      than in group 2 (21.2 +/- 5.1 vs. 8.1 +/- 3.1 ampoules). The pregnancy rate was
      20% in group 1 and 12.5% in group 2, the difference being not significant.
      CONCLUSION: The pregnancy rates were not significantly different between the GnRH
      a/hMG/ IUI and CC/hMG/IUI groups. In addition, GnRH-a/hMG stimulation is notably
      more expensive than CC/hMG, and for these reasons, GnRH-a/hMG stimulation is not
      cost-effective in routine IUI therapy.

PMID- 9243210
TI  - Interleukin-8 is a mediator of the final cervical ripening in humans.
AB  - OBJECTIVE: The aim of the present study was to investigate the presence of
      interleukin-8 (IL-8) in the human cervix and whether the levels of interleukin-8
      could be related to the ripening process during pregnancy. STUDY DESIGN: Cervical
      biopsies were obtained in twelve term pregnant and in eight vaginally delivered
      women. Seven non-pregnant fertile women served as controls. After homogenisation
      and centrifugation, IL-8 levels were determined in the supernatant by an enzyme
      immunoassay (EIA). RESULTS: In women at term, the concentration of IL-8 increased
      six-fold from median 330 pg/ml to median 2190 pg/ml (P < 0.001). After the final
      cervical ripening it increased in additional 11-fold to median 26,100 pg/ml (P <
      0.001). These changes are highly significant. CONCLUSION: To our knowledge, this
      is the first time IL-8 has been identified in human cervix. Our results support
      the involvement of IL-8 in the connective tissue remodelling during the final
      cervical ripening just before onset of labour.

PMID- 9243211
TI  - The architecture of the myosalpinx in the sow as revealed by scanning electron
      microscopy.
AB  - OBJECTIVE: To provide a definitive settlement of data on the architecture of
      myosalpinx in the sow in consideration of controversial data existing in
      literature. STUDY-DESIGN: To allow direct visualization of muscular architecture,
      segments of tube from fifteen sows were investigated by means of scanning
      electron microscopy after the removal of interstitial connective tissue with NAOH
      digestion. RESULTS: In the extramural portion of the tubo-uterine junction, in
      the isthmus and ampulla, the myosalpinx is mainly constituted by oblique bundles
      of variable length, which run around the tube and merge into the surrounding
      musculature, giving origin to a plexiform arrangement. In the ampulla the fibers
      join in short bundles variously oriented. CONCLUSION: The three-dimensional
      architecture of the sow myosalpinx consists of muscular bundles independent of
      one another which follow multiple spatial arrangements and form a complex
      network. Such a muscular structure is likely more suitable for stirring rather
      than pushing the embryo and gametes.

PMID- 9243212
TI  - Ovarian vein thrombosis with symptoms prior to term--a case report.
AB  - A case with ovarian vein thrombosis before delivery is presented. C-reactive
      protein exceeded 200 mg/l, and the patient was treated for a suspected infection
      before the true diagnosis was revealed by CT. After aggressive anti-coagulant
      therapy, a follow-up CT showed complete remission.

PMID- 9243213
TI  - Increased concentrations of plasma epinephrine and norepinephrine in patients
      with eclampsia.
AB  - We measured plasma catecholamine concentrations on admission (after eclamptic
      fit) and after 6 days of delivery in 21 eclamptic patients and on admission in 15
      normotensive pregnant women in Bangladesh. Plasma epinephrine and norepinephrine
      concentrations in eclamptic patients were significantly higher on admission than
      those of normotensive pregnant women (P < 0.0001). Plasma catecholamine
      concentrations and mean arterial blood pressure had return to be almost normal as
      normotensive pregnant women after 6 days of delivery, resulting in no correlation
      between mean arterial blood pressure and plasma catecholamines. On admission
      (after eclamptic fit) mean arterial blood pressure was positively correlated with
      plasma epinephrine (r = 0.626, P < 0.002) and norepinephrine (r = 0.553, P <
      0.008) concentrations in patients with eclampsia. The amount of proteinuria was
      also significantly correlated with plasma epinephrine (r = 0.515, P < 0.02) and
      norepinephrine (r = 0.606, P < 0.003) concentrations. Number of convulsions was
      significantly correlated with concentrations of plasma epinephrine (r = 0.514, P
      < 0.02), norepinephrine (r = 0.521, P < 0.01) and mean arterial blood pressure (r
      = 0.535, P < 0.01). A positive correlation was found between time passed after
      convulsion with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r =
      0.570, P < 0.006) concentrations. These suggested that the increased plasma
      levels of epinephrine and norepinephrine in eclamptic patients were well
      correlated with the severity of the clinical features of eclampsia.

PMID- 9243214
TI  - Prevention of amblyopia and the concept of cure.
AB  - Amblyopia is used as a comprehensive term for unexplained reduction of visual
      acuity, usually unilateral. As long as the visual deficit is monocular the visual
      loss is more of a potential problem than an actual handicap. Amblyopia is one of
      the most common causes of visual deficit in childhood, and since it is treatable,
      at least in children, considerable efforts have been made to detect it as early
      in life as possible. Screening programmes for amblyopia among preschool and
      school children have been widely organized throughout the world, although
      questions remain about their utility. This study evaluated amblyopia screening,
      focussing on some essential points that need thorough consideration before a
      screening programme is started. We also try to demonstrate some of the pros and
      cons of a screening system.

PMID- 9243215
TI  - Regression and wound healing after excimer laser PRK: a histopathological study
      on human corneas.
AB  - BACKGROUND: The results of excimer laser PRK are promising as more than 80% of
      eyes with up to -6.0 diopters of attempted correction have refractive results
      within 1.0 diopter of emmetropia. However, throughout the dioptric range some
      unexpected results have been observed with individual patients showing an
      aggressive wound healing response with excessive myopic regression and severe
      corneal haze. Unfortunately, only limited data are available about the cellular
      and extracellular responses in human corneas after PRK and this information is
      important to establish adequate postoperative pharmaceutical treatment. METHODS:
      We made a histopathological and immunohistochemical study on 20 human corneal
      samples from patients with severe corneal haze and myopic regression. The
      indirect immunofluorescence method was used for demonstration of collagen types
      I, III, IV laminin, chondroitin sulphate, dermatan sulphate, and keratin.
      RESULTS: All corneal specimens showed a hyperplastic epithelium. Histologically,
      most samples (16/20) showed mainly a loose lamination of extracellular material
      which could be identified as collagen type IV. The remaining four samples had
      newly synthesised collagen type III. CONCLUSIONS: Our histopathological results
      indicate that corneal wound healing after excimer laser PRK varies among
      individuals. In some people epithelial basement proteins, such as collagen type
      IV, are the main wound healing products, whereas in others mainly collagen type
      III is found postoperatively, which does not effect the synthesis of collagen
      type IV. This suggests the need for individually-tailored postoperative
      pharmaceutical treatment regimens.

PMID- 9243216
TI  - The role of patient's age in regression of holmium:YAG thermokeratoplasty-induced
      correction of hyperopia.
AB  - PURPOSE: Hyperopic correction can be induced with holmium:YAG laser
      thermokeratoplasty, which changes corneal curvature by shrinking stromal
      collagen. The thermal effectiveness of pulsed Ho:YAG laser depends on the water
      content of the corneal stroma, which should be related to age. This study
      investigated the presumed effect of age on the stability of the results of Ho:YAG
      laser thermokeratoplasty. METHODS: Ho:YAG laser thermokeratoplasty was done in 63
      eyes of 45 patients for low to moderate hyperopic correction (up to 5 diopters).
      Patients were treated with one or two rings of 8 spots each, with an optical zone
      of 6 or 7 mm diameters respectively. RESULTS: Regression of the therapeutic
      effect was evaluated on the basis of the difference between the attempted to
      achieved correction ratio on the first postoperative day and at the last visit.
      The regression ratio was 18% in the patients older than 20 years. Patients
      younger than 20 years showed a ratio of 48%. Achieved correction was +2.40 D in
      older patients and +2.05 in younger patients. These values are respectively 43%
      and 35% of the attempted corrections. CONCLUSIONS: It appears that age-dependent
      corneal factors do influence the effectiveness of thermal energy on stromal
      collagen.

PMID- 9243217
TI  - A comparison of two ophthalmic steroid-antibiotic combinations after cataract
      surgery.
AB  - We performed this prospective, randomised, investigator-masked, parallel-group
      study to compare Fluorometholone-Gentamicin eye drops with Maxitrol
      (dexamethasone, neomycin, polymyxin B) eye drops in the reduction of ocular
      bacterial flora and control of ocular inflammation after cataract surgery. One
      hundred and twelve (FML-Genta 54, Maxitrol 58) patients of both sexes undergoing
      cataract and posterior chamber lens implant surgery for visually disabling
      cataract were enrolled in the study and examined pre-operatively and post
      operatively on days 1, 6-8 and 24-34. The baseline parameters were similar in the
      two study groups. The conjunctival bacterial colony count on day 6-8 post
      operatively was significantly less on FML-Genta compared with Maxitrol (p =
      0.033). There was no statistically significant difference between the two
      treatments in the degree of intra-ocular inflammation as assessed by flare and
      cells in the anterior chamber. Both treatments were judged to be equal in the
      global assessment of the success of therapy and local tolerance by the study
      patients and doctors. Fluorometholone-gentamicin eye drops were more effective
      than Maxitrol eye drops in the reduction of ocular bacterial flora while being as
      well-tolerated and as effective as Maxitrol in the control of ocular inflammation
      after cataract surgery.

PMID- 9243218
TI  - Cataract surgery in Fuchs' heterochromic iridocyclitis.
AB  - PURPOSE: To assess the particularities of extracapsular cataract extraction and
      posterior chamber intraocular lens implantation in patients with Fuchs'
      heterochromic iridocyclitis. METHODS: Retrospective analysis of 24 extracapsular
      cataract operations performed from September 1991 to June 1994. Our technique-a
      slight modification of Blumenthal's technique-included a triplanar watertight
      small scleral incision, an envelope capsulotomy, nucleus hydrodissection and
      hydroexpression, anterior chamber maintainer use, thorough residual cortex
      removal through a side-port corneal incision and "in the bag" posterior chamber
      intraocular lens implantation. RESULTS: Mydriasis was slightly larger than 5 mm
      in 79.16% of the total group. Posterior capsule rupture with vitreous loss
      occurred in one and without in two patients. A transient rise in intraocular
      pressure was seen in seven patients and a mild anterior chamber reaction in
      almost all patients. No bleeding occurred during anterior chamber opening, or
      postoperative I.O.L. decentration or glaucoma. Best corrected postoperative
      visual acuity ranged from 5-10/10 in 21 patients (87.50%). CONCLUSIONS:
      Extracapsular cataract extraction in patients with Fuchs' heterochromic
      iridocyclitis does not currently present any difficulties compared with normal
      senile cataract. No major complications occurred and the final visual acuity was
      satisfactory.

PMID- 9243219
TI  - Correlation between ocular hypertension induced by ibopamine and perimetric
      defect in primary open-angle glaucoma.
AB  - In 35 patients with bilateral primary open-angle glaucoma (POAG), with
      asymmetrical evolution of the neuropticopathy between the two eyes, we compared
      within each patient, the response to ibopamine and the perimetric defect. In 88%
      of cases (31/35 patients) the eye with the most severe perimetric defect had high
      intraocular pressure or a larger IOP increase after ibopamine. This result was
      highly significant at the sign test (P < 0.001). IOP and its increase after
      ibopamine significantly differed in the most and least affected eye, being higher
      in the eye with the most impaired visual field. Since ibopamine can be used to
      quantify the hydrodynamic impairment, which is thus presumably correlated to the
      perimetric defect. This study further confirms its importance in the development
      of glaucomatous damage.

PMID- 9243220
TI  - Diabetic retinopathy and cerebral hemodynamic impairment in type II diabetes.
AB  - PURPOSE: To assess whether a screening method based on transcranial Doppler (TCD)
      examination could detect signs of brain hemodynamic impairment in non-insulin
      dependent diabetic patients with retinal microangiopathy of varying severity,
      asymptomatic for cerebrovascular diseases. METHODS: We studied 86 patients
      stratified according to the presence of proliferative diabetic retinopathy (PDR:
      29 cases), background retinopathy (BDR: 32 cases) and no diabetic retinopathy
      (NDR: 25 patients). TCD was performed to record mean flow velocity and
      pulsatility index values in the middle cerebral (MCA), anterior cerebral (ACA)
      and ophthalmic arteries (OA), at rest. It was also employed to evaluate the
      cerebral vasodilatory response to a breath-holding test: the maximum percentage
      MCA flow velocity increase during the test was taken as an index of
      cerebrovascular reactivity. Fifty healthy subjects were studied to establish
      control values. Analysis of variance was used to test inter-group differences.
      The regression test was applied to define the relationship between TCD parameters
      and age and disease duration. RESULTS: No significant differences were found
      between controls and the whole group of patients with respect to TCD parameters.
      However, subgroup analysis showed PDR patient had a significantly higher
      pulsatility index and lower cerebrovascular reactivity than BDR and NDR patients.
      This difference was not explained by the effect of age or disease duration, being
      greatest in patients under sixty. CONCLUSIONS: These findings seem to confirm the
      hypothesis of a silent cerebral microangiopathy affecting diabetic patients, with
      concomitant signs of microangiopathic damage in other districts.

PMID- 9243221
TI  - Exploration of Vogt-Koyanagi-Harada syndrome by infrared choroidal angiography
      with indocyanine green.
AB  - The choroid affected by the Vogt-Koyanagi-Harada syndrome (VKH) has seldom been
      explored by indocyanine green choroidal angiography. Five patients with definite
      diagnosis of VKH underwent this investigation. The first case had the most marked
      leakage, very similar to that on fluorescein angiography. The right eye of case 2
      showed fewer leakage points on ICG than on fluorescein angiography, compared with
      case 1. The left eye of case 2 did not show any leakage. Cases 3, 4 and 5 yielded
      segmental hyperfluorescence, distant from the posterior pole, which could not be
      identified by fluorescein angiography. This might indicate segmental choroiditis.
      There were two types of hypofluorescent lesions; all the cases except case 2
      showed early hypofluorescence. Hypofluorescent areas corresponding to overlying
      retinal detachment were seen in the right eye of case 4. Multiple spots, late
      hypofluorescence, about 200 to 500 um in size appeared throughout the posterior
      pole in four eyes out of ten. In conclusion, indocyanine green choroidal
      angiography provides a wider variety of pictures than fluorescein angiography.

PMID- 9243223
TI  - Boxing and the eyes: morphological aspects of the ocular system in boxers.
AB  - Among all sports, the so-called "contact sports" are those in which the athlete's
      eye is particularly at risk. In boxing, where the face is the main target, the
      eye is clearly one of the most exposed parts. To assess the eye risks in this
      sport a study was carried out between 1992 and 1994 at the Ophthalmological
      Clinic of the university of Turin, Italy, involving 75 active and ex-boxers
      (amateurs and professionals) aged 15 to 70 years. Biomicroscopic examinations,
      refraction and acuity tests, tonometry, exophthalmometry, gonioscopy, ocular
      fundus examination with Goldmann three-mirror lens) were done. The results of the
      survey confirm the existence of alterations, generally asymptomatic, both in
      amateur and professional boxers. The eye examination showed alterations of
      structures such as the orbital arch, conjunctiva, iris, lens, retina. Four boxers
      had retinal detachment, three of them due to boxing. The opthalmologist has an
      important part to play in preventing serious damage to the eye and in checking
      alterations which might be an expression of subtle neural damage (pupillary
      alterations).

PMID- 9243222
TI  - Iris diaphragm implantation in post-traumatic aniridia and tractional retinal
      detachment.
AB  - The implantation of an artificial iris diaphragm is described in a case of
      aniridia and traumatic aphakia with a relapsed, tractional retinal detachment.
      The addition of heparin and dexamethasone to the infusion liquid is useful to
      reduce the fibrinous exudation which seems to be the main cause of diaphragm
      obliteration.

PMID- 9243224
TI  - Is tear calcium an indicator of ocular calcification in patients with chronic
      renal failure?
AB  - BACKGROUND: In patients with chronic renal failure (CRF) on regular dialysis
      treatment, limboconjunctival degeneration and calcifications are common. The
      mechanisms of ectopic conjunctival and corneal calcification remain largely
      speculative. The aim of the present work was to study tear calcium levels in
      patients with chronic renal failure, which could alter calcium excretion
      patterns, and to examine whether the calcium level in tear fluid is of more
      diagnostic importance than static calcium levels in blood. METHODS: Tear calcium
      levels were measured in 25 patients with chronic renal failure, compared with 14
      normal subjects. Conjunctival and corneal calcium deposits were graded by the
      Porter and Crombie classification. RESULTS: While 11 of the 25 patients had no
      clinically apparent calcium deposits, six had Grade 1 or 2, and eight had Grade 3
      and over limboconjunctival calcification. Mean tear calcium levels were 1.436 +/-
      0.165 mg/dl in the patients and 1.307 +/- 0.155 mg/dl in the normal group. The
      difference was not significant (P = 0.572). No correlation was found between the
      grade of the calcium deposits and tear calcium levels. CONCLUSIONS: Tear calcium
      level has no diagnostic importance for the development of ocular calcification in
      chronic renal failure.

PMID- 9243225
TI  - Oral low-dose midazolam as premedication for intraocular surgery in retrobulbar
      anesthesia: cardiovascular effects and relief of perioperative anxiety.
AB  - The aim was to investigate the efficacy and practicability of oral low-dose
      premedication with 3.75 mg midazolam (1/2 tablet Dormicum 7.5 mg) for selective
      intraocular surgery with retrobulbar anesthesia. Forty-six ASA II-III patients
      were randomly assigned to either group I: midazolam (n = 24) or group II: placebo
      (n = 22). Sedation was objectively quantified with a scale derived from the
      Glasgow-Coma-Scale and a verbal self-rating scale. Trait-anxiety was studied with
      the State-Trait Inventory by Spielberger, perioperative situative anxiety with
      the Erlanger Anxiety Scale. Cardiovascular variables and oxygenation were
      automatically monitored. Midazolam produced significant and sufficient sedation
      and significant anxiolysis. Systolic, diastolic and mean blood pressure were
      moderately but significantly, reduced. The effect on diastolic pressure was more
      pronounced. There was no effect on heart-rate. Oxygenation at all times remained
      well above 90% SpO2. In conclusion low-dose oral midazolam proved to be a single
      and effective premedication before intraocular surgery under local anesthesia.

PMID- 9243226
TI  - A case of Duane's retraction syndrome with multiple congenital malformations.
AB  - Duane's retraction syndrome is associated with various ocular and systemic
      abnormalities. We report a case with bilateral Duane's retraction syndrome type I
      accompanied by renal agenesis, vesico-ureteral reflux, patent ductus arteriosus,
      and external ear malpositioning. Because of disabling consequences, we recommend
      a thorough physical examination and screening for renal and cardiac abnormalities
      in all patients presenting with Duane's reaction syndrome.

PMID- 9243227
TI  - OCT images and surgery of juvenile Macular retinoschisis.
AB  - We describe three cases of X-linked juvenile retinoschisis confined to the
      posterior pole of the eye, one of which surgically treated. In the first two
      cases, in vivo optical coherence tomography (OCT) had revealed a cleavage plane
      in both nerve fiber and outer retinal layers. In the two similar operated eyes of
      the third case, postoperative OCT had revealed the disappearance of macular
      schisis in the eye with good recovery of visual function after surgery. On the
      contrary, it had revealed a persistent splitting of the retina in the other eye,
      not clinically visible, which explained the poor recovery of visual function
      after surgery. In cases with progressive worsening of macular involvement in X
      linked juvenile retinoschisis, highly accurate surgery may be considered, and the
      pre- and postsurgical OCT monitor of these patients is indicated.

PMID- 9243228
TI  - Primary hyperoxaluria type 2.
AB  - Primary hyperoxaluria type 2 (PH2) is a rare disease with only 24 patients
      reported in the literature so far. It should be considered in any patient
      presenting with urolithiasis or nephrocalcinosis due to hyperoxaluria. The
      metabolic defect is deficiency of D-glycerate dehydrogenase/glyoxylate reductase
      leading to characteristic hyperoxaluria and excretion of L-glycerate, the
      cornerstone of diagnosis of PH 2. Although development of terminal renal failure
      seems to be less prevalent than in PH 1, recent reports indicate that chronic as
      well as terminal renal insufficiency may occur. Therefore specific therapeutic
      measures should aim at reduction of urinary calcium oxalate saturation by
      potassium citrate or pyrophosphate to reduce the incidence of nephrolithiasis and
      nephrocalcinosis and thus improve renal survival. Secondary complications
      (obstruction, urinary tract infections and pyelonephritis) must be avoided. In
      patients with terminal renal failure isolated renal transplantation seems to
      carry a high risk of disease recurrence. CONCLUSION: PH 2 is a rare but important
      cause of urolithiasis and nephrocalcinosis; long-term follow up is necessary,
      since the renal prognosis may be worse than previously anticipated.

PMID- 9243229
TI  - The attitude against immunisation within some branches of complementary medicine.

PMID- 9243230
TI  - The value of MRI in diagnosing vascular abnormalities causing stridor.
AB  - In a 2 year period seven patients who presented with stridor, without respiratory
      compromise, and three patients without obstructive symptoms were prospectively
      selected, and underwent MRI. In eight patients with a vascular ring and a
      pulmonary sling, MRI delineated the vascular abnormality and normal great vessels
      were found in two patients. CONCLUSION: MRI successfully delineates the great
      vessels and demonstrates the presence of a vascular ring and pulmonary sling.

PMID- 9243231
TI  - Management with a staged approach of the premature hydropic fetus due to complete
      congenital heart block.
AB  - The management of the preterm fetus with hydrops due to complete congenital heart
      block is difficult. The outcome is frequently associated with significant
      morbidity and mortality. Two fetuses presented at the post menstrual age of 29
      and 30 weeks respectively with severe hydrops due to complete heart block. The
      following staged approach was adopted: (1) enhance fetal lung maturation with
      maternal corticosteroids and thyroid releasing hormone for 48 h; (2) elective
      Caesarean section; (3) classical neonatal management consisting of intubation and
      ventilation, drainage of all cavities with effusions; (4) increase neonatal heart
      rate by administration of i.v. isoprenaline, by bipolar trans-oesophageal pacing
      or epicutaneo-oesophageal pacing; (5) after the regression of the hydrops, start
      epicardial pacing after implantation of 2 or 3 temporary epicardial 3/0
      pacemaker; (6) implantation of a permanent abdominal pacing system with steroid
      epicardial tip once the threshold exceeds 20 mA or when the baby weighs more than
      1500 g. In these patients a permanent pacing system was implanted at the ages of
      8 weeks (2045 g) and 4 weeks (1560 g) respectively. No major complications
      occurred; the cardiac outcome with 37 and 34 months of follow up is excellent.
      CONCLUSION: This proposed staged approach with temporary epicardial leads can
      improve the outcome of hydropic fetuses due to complete congenital AV block.

PMID- 9243232
TI  - Late manifestation of diabetes insipidus in "pure" cutaneous Langerhans cell
      histiocytosis.
AB  - We report a case of congenital Langerhans cell histiocytosis (LCH), presenting
      with a generalized varicelliform rash in an otherwise well newborn. No signs of
      organ involvement were found on repeated skeletal radiography, abdominal
      ultrasonography and laboratory studies. A diagnosis of "pure cutaneous" LCH was
      established. Skin manifestation was unusually severe and recurred during the
      first 20 months of life, but responded well to combination chemotherapy
      (methylprednisone, vinblastine) while the child continued to thrive. At the age
      of 2 years the patient presented with acute onset diabetes insipidus due to
      infiltration of the hypothalomo-pituitary stalk region. He died for reasons
      unknown at the age of 28 months. CONCLUSION: "Pure cutaneous" LCH, frequently
      also referred to as congenital self-healing LCH, is a variable disorder which may
      be complicated by late organ involvement. Close follow up and thorough diagnostic
      evaluation is therefore mandatory.

PMID- 9243233
TI  - An immunocompetent infant with cow's milk allergy and cytomegalovirus colitis.
AB  - A 5-week-old, severely ill, infant is described with diarrhoea and rectal
      bleeding, followed by vomiting and dehydration after introduction of a cow's milk
      formula. A diagnosis of cow's milk allergy was made because of the clinical
      presentation of an allergic enterocolitis, the rapid improvement after
      introduction of a hypo-allergenic formula and development of colic directly after
      rechallenge with cow's milk. Furthermore a highly specific IgE for alpha
      lactalbumin strongly supported the diagnosis. Because of recurrent rectal
      bleeding a limited colonoscopy was performed at the age of 10 weeks. Surprisingly
      a second diagnosis of histopathologically proven cytomegalovirus (CMV) colitis
      was made. Extensive immunological screening revealed no signs of
      immunodeficiency. The child thrived without any treatment for CMV and developed
      normally. This is the first description of an immunocompetent infant with CMV
      colitis. CONCLUSION: It cannot be excluded that the allergic colitis facilitated
      the CMV colitis, or vice versa CMV colitis triggered cow's milk protein induced
      entero-colitis. Further attention should be given to children with bloody
      diarrhoea to establish a possible relationship between CMV infection and cow's
      milk protein allergy.

PMID- 9243234
TI  - Oesophageal intramural pseudodiverticulosis: a cause of dysphagia in a 10-year
      old boy.
AB  - We report a 10-year-old boy who presented with a piece of chicken stuck in his
      throat. He had similar episodes in the past that resolved spontaneously. The
      foreign body was removed and oesophagoscopy revealed no abnormality. Post
      operative barium swallow showed oesophageal intramural pseudodiverticulosis.

PMID- 9243235
TI  - Continuous plasma resin perfusion for detoxification of methotrexate.
AB  - Acute renal failure is a rare but very severe side-effect of methotrexate (MTX)
      treatment requiring extracorporeal detoxification. A new detoxification regime,
      consisting of a haemodiafiltration (HDF) and continuous plasma resin perfusion
      (PRP) over anion exchange resin column with high affinity for MTX, was used for
      treatment of MTX-induced acute renal failure in a 2-year-old boy with
      medulloblastoma. More than 99% of MTX was removed from plasma by perfusion over
      the resin column resulting in a marked decrease of MTX plasma half-life. No
      haematological complications occurred. CONCLUSION: The use of PRP alone or in
      combination with HDF is a new and effective treatment strategy for extracorporeal
      detoxification of MTX.

PMID- 9243236
TI  - Circulating soluble adhesion molecule levels in children with acute lymphoblastic
      leukaemia.
AB  - The aim of this study was to evaluate levels of serum soluble intercellular
      adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM
      1) and soluble E-selectin (sE-selectin) as parameters of disease activity and to
      monitor the response to treatment in children with acute lymphoblastic leukaemia
      (ALL). The above soluble adhesion molecules were determined in the serum of 35
      children with ALL and 30 healthy children (control group) of the same age range.
      The samples were obtained before treatment, 6 months after the beginning of the
      treatment (remission of the disease), 6 months after the end of the treatment and
      during relapse of the disease. The mean levels of sICAM-1, sVCAM-1 and sE
      selectin at the onset of the disease were 646.6 +/- 80.9 ng/ml, 1786 +/- 151.8
      ng/ml and 140.5 +/- 17.3 ng/ml, respectively. These values were significantly
      higher (P < 0.001) than those of the control group, which were, 245.8 +/- 25.7
      ng/ml, 798.6 +/- 78.9 ng/ml and 44.7 +/- 18.2 ng/ml respectively. During
      remission, the mean levels did not differ significantly from those of the control
      group. After the end of the treatment the mean levels again did not show any
      significant differences compared to the control group. During relapse the soluble
      adhesion molecule mean levels (923.9 +/- 110.1 ng/ml, 2945.7 +/- 349.9 ng/ml and
      258.2 +/- 5.1 ng/ml) were significantly higher (P < 0.001) than those of the
      control group and also than those obtained during remission and after the end of
      the treatment (P < 0.001). Pearson's correlation coefficient r was computed in
      order to detect possible linear correlations between: (1) sICAM-1 and sVCAM-1 (r
      = 0.632); (2) sICAM-1 and sE-selectin (r = 0.788) and (3) sVCAM-1 and sE-selectin
      (r = 0.752). All three cases correspond to P < 0.001, thus indicating strong
      linear correlations. CONCLUSIONS: The levels of soluble circulating adhesion
      molecule levels can be utilized for monitoring disease activity of ALL and its
      response to treatment, as well as for early detection of relapse. Strong linear
      correlations between the three soluble adhesion molecules tested suggest that
      each of them may be sufficient as an indicator.

PMID- 9243237
TI  - Epidemiology of encephalitis in children. A prospective multicentre study.
AB  - We found 175 cases with acute encephalitis in a population of 791,712 children
      aged 1 month-15 years during a 2-year surveillance period in 1993-1994. The
      overall incidence was 10.5/100,000 child-years with the highest figure in
      children < 1 year of age, 18.4/100,000 child-years. The microbial diagnosis was
      considered proven or suggested in 110 cases (63%); varicella zoster, respiratory
      and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes
      simplex and rota viruses comprised 5% each. A clearcut change seems to have
      occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus
      associated encephalitides have been almost eliminated. Varicella zoster,
      respiratory, and enteroviruses have increased in frequency and occur in younger
      age groups. New causes were identified, especially Chlamydia pneumoniae and HHV
      6. Our data should assist in making a specific diagnosis and defining appropriate
      antimicrobial therapy. CONCLUSIONS: The spectrum of encephalitis in children has
      changed due to vaccination programs. The incidence, however, appears to be about
      the same due to increasing frequency of other associated old and new microbes.

PMID- 9243238
TI  - Hepatitis C and G virus infections in polytransfused children.
AB  - The prevalence of hepatitis C virus (HCV) and a newly identified hepatitis G
      virus (HGV) and their clinical significance were studied in 42 polytransfused
      Taiwanese children. Serological assays for antibodies against HCV (anti-HCV) and
      polymerase chain reaction for serum HCV ribonucleic acid (RNA) and HGV RNA were
      performed. The prevalence of anti-HCV and HGV RNA was 17% and 14%, respectively
      in 42 polytransfused children. Anti-HCV seropositives had a significantly higher
      mean age, peak serum transaminase level, and longer transfusion duration than
      seronegatives, while children with HGV infection usually had no or only mild
      hepatitis activities. The prevalence of anti-HCV dropped sharply after
      implementation of anti-HCV screening, however the prevalence of HGV viraemia
      remained unchanged. CONCLUSIONS: HGV infection is not uncommon in polytransfused
      Taiwanese children and the virus does not cause significant hepatitis compared to
      HCV infection. Current blood donor screening for anti-HCV can effectively protect
      polytransfused children from HCV infection but the impact of additional screening
      for HGV markers awaits further studies.

PMID- 9243239
TI  - Invasive antenatal procedures and requirement for neonatal intensive care unit
      admission.
AB  - Neonatal respiratory difficulties are increased following second trimester
      amniocentesis. In preterm, prolonged rupture of the membranes, respiratory
      outcome is particularly poor when rupture occurs in the first trimester. It
      therefore seems likely that first trimester/ early amniocentesis (EA) would be
      associated with severe respiratory problems necessitating a high neonatal
      intensive care unit (NICU) admission rate. To test that hypothesis, the
      requirement for admission to the NICU of 278 infants whose mothers had undergone
      EA, 262 whose mothers had undergone chorion villus sampling (CVS group) and 264
      controls whose mothers had undergone no invasive procedures were reviewed as were
      their diagnoses if they needed admission. There was no significant difference in
      the mode of delivery, gestational age or gender distribution of the three groups
      and the median maternal age of the EA and CVS groups was similar. Nineteen EA,
      eight CVS and five control infants required admission to the NICU (EA versus
      controls, P < 0.01; EA versus CVS plus controls, P < 0.005). Nine EA, one CVS and
      four control infants had suffered respiratory problems (EA versus CVS P < 0.05).
      Logistic regression analysis demonstrated that immaturity and EA were
      significantly associated with a requirement for NICU admission. We conclude
      infants whose mothers have undergone EA may be at increased risk for NICU
      admission, this is partly due to respiratory problems but the association is
      uncommon.

PMID- 9243240
TI  - Effects of red cell transfusion on pulmonary blood flow and right ventricular
      systolic time intervals in neonates.
AB  - Blood transfusion increases blood volume and blood viscosity of the neonate.
      Since both volume expansion and increase in blood viscosity may be associated
      with increased pulmonary artery pressure, we studied effects of transfusion (10
      ml of red blood cells per kilogramme of body weight) on right ventricular output
      and right systolic time intervals by means of pulsed-Doppler echocardiography in
      38 preterm infants with a mean (SD) gestational age of 28 (5) weeks (range 25
      34), birth weight 1060 (395) g (range 480-1910), actual body weight 1875 (450) g
      (range 820-2790) and postnatal age of 44 (23) days (range 17-105). After
      transfusion, packed cell volume and haemoglobin increased significantly from 0.26
      (0.044) to 0.38 (0.046), and from 8.2 (1.6) g/l to 12.8 (1.9), respectively.
      Blood viscosity increased from 1.78 (0.3) mPa to 2.68 (0.4) by 33%. Right
      ventricular output decreased significantly from 320 (57) ml/kg/min to 290 (70)
      due to decrease in heart rate by 7%. Blood pressure and right ventricular stroke
      volume did not change. There was a significant increase in pulmonary red cell
      transport (right ventricular output times packed cell volume) of 21%. Right
      ventricular pre-ejection period (RPEP), right time peak velocity (RTPV), right
      ventricular ejection time (RVET), and ratios of RTPV/RVET(c). RPEP:RVET did not
      change after transfusion. CONCLUSIONS: These results suggest that neither
      pulmonary artery pressure nor right ventricular function changed as a result of
      transfusion in spite of rising blood volume and blood viscosity.

PMID- 9243241
TI  - Topographic mapping of brain electrical activity in children with food-induced
      attention deficit hyperkinetic disorder.
AB  - In 15 children suffering from food induced attention deficit hyperkinetic
      syndrome, topographic EEG mapping of brain electrical activity was carried out
      following avoidance and ingestion of previously identified provoking foods. A
      crossover design was used and recordings were interpreted independently by two
      investigators, one of whom was blind to the order of testing. During consumption
      of provoking foods there was a significant increase in betal activity in the
      frontotemporal areas of the brain. This investigation is the first one to show an
      association between brain electrical activity and intake of provoking foods in
      children with food-induced attention deficit hyperactivity disorder. CONCLUSIONS:
      These data support the hypothesis that in a subgroup of children with attention
      deficit hyperactivity disorder certain foods may not only influence clinical
      symptoms but may also alter brain electrical activity.

PMID- 9243242
TI  - Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS) triggered by valproate therapy.
AB  - We report in this study a patient who developed repeated convulsions as a result
      of valproate therapy. MELAS (mitochondrial myopathy, encephalopathy, lactic
      acidosis and stroke-like episodes) was subsequently diagnosed and a nucleotide
      3243 A-->G mutation was detected in the mitochondrial DNA. This mutation
      predisposes the patient to the detrimental effects of valproate on oxidative
      phosphorylation. CONCLUSION: We support the suggestion of Ponchaut et al. [14]
      that valproate should not be given to patients suspected of having mitochondrial
      diseases. In addition, for patients whose seizures worsen with valproate therapy,
      an inborn error of mitochondrial metabolism should be suspected. The underlying
      mitochondrial DNA defects should be sought for family screening and genetic
      counselling.

PMID- 9243243
TI  - Serum lipids in epileptic children treated with carbamazepine and valproate.
AB  - Serum total cholesterol (TC), high-density lipoprotein (HDL-C), low-density
      lipoprotein (LDL-C) and very low-density lipoprotein cholesterol, triglyceride,
      apolipoproteins A1 and B levels were studied in 57 healthy children and in 39
      children with epilepsy who had been receiving carbamazepine (CBZ) (23 children)
      for 1.58 +/- 1.10 years or valproic acid (VPA) (16 children) for 1.34 +/- 1.11
      years. In patients receiving CBZ, mean TC level, mean LDL-C level, mean TC/HDL-C
      ratio and mean LDL-C/HDL-C ratio-were significantly higher than controls. None of
      the mean levels of serum lipids evaluated in patients receiving VPA was
      significantly different from the corresponding control group mean. Changes in
      serum lipids correlated with neither duration of therapy or plasma antiepileptic
      levels nor age or gender. CONCLUSION: Our results suggested that CBZ, a
      hepaticenzyme-inducing drug, affects serum lipid status. Long-term prospective
      studies are necessary to determine whether chronic CBZ therapy is a risk factor
      for atherosclerotic disorders.

PMID- 9243244
TI  - A 7-year-old child with primary tumour localisation in the distal duodenum--new
      imaging procedures for an improved diagnosis.
AB  - Duodenal gastrinomas in childhood are extremely rare and often missed at first
      medical consultation. We report on a 7-year-old child with sporadic gastrinoma of
      primary localisation in the distal duodenum. Small metastases in the liver and
      regional nodes were detected pre-operatively by somatostatin receptor
      scintigraphy (SRS) but not by other conventional imaging procedures. Diagnostic
      procedures include pre-operative SRS, endoscopic ultrasound and intra-operative
      endoscopic transillumination. CONCLUSION: Gastrinomas are rare abdominal tumours
      in childhood. Pre-operative tumour-specific diagnosis is possible by 111indium
      pentreotide SRS.

PMID- 9243245
TI  - Congenital bilateral agenesis of diaphragm: report of a case.
AB  - Bilateral agenesis of the diaphragm is a rare, life-threatening malformation.
      Infants with this defect rarely survive to have surgical intervention. We report
      a 32-week premature female infant who was born to a 36-year-old mother via
      vaginal delivery. The pregnancy course was complicated by hypertension and
      polyhydramnios. Cytogenetic study showed a normal 46 XX female karyotype. She had
      cyanosis, respiratory distress and scaphoid abdomen at birth. A roentgenograph
      confirmed the diagnosis of diaphragmatic hernia. Surgery was performed at 21 h of
      age. Bilateral agenesis of diaphragm, herniation of abdominal organs and
      oesophagus and pulmonary hypoplasia were noted. Furthermore, stomach and spleen
      were adherent to the mediastinum and vertebrae. The patient developed hypotension
      and persistent hypoxaemia and expired at age of 26 h. Autopsy revealed bilateral
      agenesis of diaphragm, hypoplasia of lungs, and pancreas fibrosis with mild
      hypoplasia of islets of Langerhans. CONCLUSION: Bilateral agenesis of diaphragm
      associated with pancreas fibrosis is a rare entity, and its clinical significance
      needs further investigation.

PMID- 9243246
TI  - Metabolites of nitric oxide in the lower respiratory tract of children.
AB  - Nitric oxide (NO) is produced in the upper and lower respiratory tract and can be
      detected in exhaled air of both healthy individuals and subjects with pulmonary
      diseases. Recent studies have shown that exhaled NO is mainly derived from the
      upper airways. There is, however, evidence that in aqueous solutions NO is
      rapidly converted to distinct oxides of nitrogen. We therefore studied the stable
      NO metabolites nitrate and nitrite in broncho-alveolar lavage (BAL) fluid and
      serum as indicators of NO formation in the lower respiratory tract. The study
      population consisted of 31 healthy children undergoing elective surgery for non
      pulmonary illnesses and 13 immunosuppressed children with pneumonia. Nitrate and
      nitrite were determined photometrically. Nitrate was found in BAL fluid of all
      children. In children with pneumonia, nitrate concentrations in BAL fluid were
      significantly higher than in healthy children. A significant correlation was
      observed between nitrate in BAL fluid and serum of immunosuppressed children with
      pneumonia. Nitrite was not detected in any of the BAL fluid or serum samples.
      CONCLUSIONS: Our results suggest that in the lower airways significant amounts of
      NO are metabolised to nitrate. Studies on NO in pulmonary diseases should
      therefore include determination of nitrate in lower airway fluids.

PMID- 9243247
TI  - Case of the month: an 8-year-old girl with clumsiness, grip weakness, and
      hypoplasia of the right hand.

PMID- 9243248
TI  - Eosinophilic colitis: a differential diagnosis of allergic colitis.

PMID- 9243249
TI  - Renal function in preterm infants.

PMID- 9243250
TI  - Cholinesterase activity in pig airways and epithelial cells.
AB  - Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC
      3.1.1.8) activities were detected in bronchial and bronchial epithelial cell
      homogenates of the pig. In the bronchial homogenates, the maximal upstroke
      velocity (Vmax) of AChE and the maximal velocity after second substrate fixation
      (Vss) of BChE were 5.70 +/- 0.46 and 7.87 +/- 0.81 mU/mg protein, respectively.
      In the epithelial cell homogenates, a smaller amount of cholinesterase (ChE) was
      found: Vmax was 0.62 +/- 0.29 and Vss was 1.56 +/- 0.33 mU/mg protein for AChE
      and BChE, respectively. AChE activity was increased by 21 +/- 5% in the bronchial
      homogenates and by 54 +/- 14% in the epithelial cell homogenates, when intact
      bronchial segments were incubated with a cyclooxygenase inhibitor, indomethacin
      (INDO). These results suggest that prostanoids may be involved in the regulation
      of AChE activity in pig airways.

PMID- 9243251
TI  - Stress-induced alterations of somatodendritic 5-HT1A autoreceptor sensitivity in
      the rat dorsal raphe nucleus--in vitro electrophysiological evidence.
AB  - Somatodendritic 5-HT1A autoreceptors play a key role in the control of the
      electrical and metabolic activity of serotoninergic neurons in the dorsal raphe
      nucleus. These neurons also possess intracellular glucocorticoid receptors which
      may be involved in the well established modulation of serotonin (5
      hydroxytryptamine, 5-HT) metabolism by corticosterone in stressed animals. The
      possible mediation by somatodendritic 5-HT1A autoreceptors of such corticosterone
      dependent changes in serotoninergic neuron activity was investigated using an in
      vitro electrophysiological approach. 5-HT1A autoreceptor-mediated inhibition of
      the firing of serotoninergic neurons was examined in brain stem slices from rats
      whose serum corticosterone concentrations had been markedly increased (+100-200%)
      by two different stressful conditions. Immobilization for 30 or 90 min (restraint
      stress) did not modify the concentration-dependent inhibition of the firing of
      serotoninergic neurons by the 5-HT1A receptor agonist ipsapirone. In contrast,
      placing the rats in novel uncontrolled environmental conditions for 16 h
      significantly reduced the cell response to ipsapirone, indicating a decreased
      sensitivity of somatodendritic 5-HT1A autoreceptors. Such a change was not
      observed in adrenalectomized rats subjected to the same stressful conditions.
      These data show that some forms of stress can reduce the 5-HT1A autoreceptor
      dependent inhibitory control of the electrophysiological activity of
      serotoninergic neurons in the dorsal raphe nucleus. Both the nature and duration
      of stress seem to be critical factors for triggering the (corticosterone
      dependent) mechanism(s) responsible for the functional desensitization of 5-HT1A
      autoreceptors in stressed rats.

PMID- 9243252
TI  - Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret
      papillary muscles during acidosis.
AB  - Acidosis affects multiple steps in the excitation-contraction coupling pathway of
      myocardium, producing decreased calcium sensitivity of myofibrils and
      modification of the function of the sarcoplasmic reticulum. Our aim was to
      evaluate the effectiveness of three different classes of inotropic agents under
      acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances
      cellular cyclic AMP concentrations, 2) elevated extracellular Ca2+ and 3)
      endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway.
      Ferret papillary muscles were mounted in organ baths containing normal
      physiological solution (pH = 7.4). After baseline tension was measured, the
      muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to
      40% of the control; subsequently, the muscles were washed with normal
      physiological solution until they returned to baseline. Each inotropic agent was
      added to the bathing solution in a concentration sufficient to increase tension
      by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the
      continuous presence of that concentration of inotropic agent and the resultant
      steady-state developed tension measured. The increases in tension induced by each
      inotropic agent at normal pH were adjusted to be similar: in contrast, the
      response to each drug in acidosis was significantly different. Under acidotic
      conditions, endothelin-1 was the most effective inotropic agent in restoring the
      depressed developed tension. This was possibly due to enhancement of the
      myofilament sensitivity to Ca2+, which was more effective than increasing [Ca2+]i
      through elevating extracellular Ca2+ or the addition of forskolin which increased
      [Ca2+]i but desensitized the myofilaments to Ca2+.

PMID- 9243254
TI  - Involvement of a CCK-dependent capsaicin-sensitive afferent pathway in the
      inhibitory effect of pinaverium bromide on the colonic motor response to eating
      in rats.
AB  - The effects of pinaverium bromide on the stimulation of colonic motility induced
      by meal and cholecystokinin (CCK) were investigated in rats chronically fitted
      with intraparietal electrodes on the proximal colon and previously treated or not
      by capsaicin. Pinaverium bromide inhibited in a dose-related manner (2-50 mg/kg,
      per os) the increase in colonic spike burst frequency induced by a 3 g meal or
      CCK-8 (2 micrograms/kg, i.v.). The CCK-A and CCK-B antagonists, devazepide and L
      365260 (100 micrograms/kg, i.p.), respectively, inhibited the postprandial
      colonic motor response while only L 365260 reduced the CCK-induced stimulation.
      The effects of pinaverium bromide and CCK antagonists were not observed in
      capsaicin-treated animals. Moreover, CCK-8 (2 micrograms/kg, i.v.) did not
      stimulate colonic motility after capsaicin treatment. The inhibition of
      postprandial colonic motility by pinaverium bromide, given orally at therapeutic
      doses, involves a CCK-dependent pathway which requires the integrity of capsaicin
      sensitive afferents.

PMID- 9243255
TI  - Effects of octreotide on experimental neurogenic orthostatic hypotension in
      anaesthetized dogs.
AB  - This paper investigates the effects of octreotide (0.1 mg/kg, subcutaneous) on
      cardiovascular adaptation during head-up tilt test in an experimental model of
      neurogenic orthostatic hypotension (OH) obtained by chronic sinoaortic
      denervation in anaesthetized dogs. Blood pressure (BP), heart rate (HR), spectral
      variability (Fast Fourier transformation on 512 consecutive points, delta t: 2
      Hz) and plasma catecholamine levels were measured in a double blind cross-over
      randomized study versus placebo, in supine position and during a head-up tilt
      test (80 degrees, 10 min) in six sinoaortic denervated and six control (normal)
      dogs. In normal dogs, head-up tilt test significantly increased HR and diastolic
      blood pressure (DBP). Plasma noradrenaline levels and energy of the low frequency
      band (40-150 mHz) of systolic blood pressure (SBP) significantly increased
      whereas the energy of the low frequency band of HR significantly decreased.
      Placebo and octreotide failed to modify supine and head-up tilt values of the
      measured parameters (except the value of low frequency band of SBP, which
      increased after octreotide). In sinoaortic denervated dogs, supine values of BP,
      HR and plasma noradrenaline levels were significantly higher than in controls
      whereas the energy of the low frequency spectral band of HR and SBP was similar
      to controls. Head-up tilt test induced a dramatic decrease in BP. HR, plasma
      noradrenaline levels and energy of the low frequency band of SBP and HR remained
      unchanged during head-up tilt tests. Neither supine nor head-up tilt values of
      these parameters were modified 45 min after octreotide or placebo administration.
      These results show that sinoaortic denervation is a reproducible model of OH
      characterized by a lack of activation of sympathetic efferent pathways during
      head-up tilt tests. Octreotide at the dose used remains ineffective to prevent
      the fall in BP under these experimental conditions.

PMID- 9243253
TI  - Response of large and small vessels to alpha and beta adrenoceptor stimulation in
      heart failure: effect of angiotensin converting enzyme inhibition.
AB  - The increased sympathetic drive in chronic heart failure (CHF) might provoke
      vascular adrenoceptor desensitization, which, together with endothelial
      dysfunction, could contribute to the altered vasomotor tone seen in CHF. We
      investigated 1) whether CHF alters the responses mediated by alpha and beta
      adrenoceptors in small and large peripheral arteries, and 2) the effect of
      angiotensin-converting enzyme (ACE) inhibition. Rats with CHF (coronary artery
      ligation) were treated with placebo or the ACE inhibitor lisinopril (10 mg/kg/d)
      starting 7 days after ligation. Responses to phenylephrine (alpha 1 agonist),
      salbutamol (beta 2 agonist) as well as acetylcholine (endothelium-dependent),
      were assessed after 3 months in isolated and pressurized segments of the
      abdominal aorta, the femoral and the mesenteric arteries. In animals with
      hemodynamic signs of CHF, neither the vasoconstrictor responses to phenylephrine
      nor the vasodilator response to salbutamol were affected. In contrast, the
      dilator response to acetylcholine of both small arteries, but not that of the
      aorta, was impaired. Furthermore, CHF did not modify vessel structure. While
      lisinopril did not modify the responses to adrenergic agonists, it normalized the
      response to acetylcholine. Furthermore, ACE inhibition reduced vascular media
      cross sectional area and collagen density. Thus, the unchanged arterial
      responsiveness to adrenoceptor agonists does not indicate any vascular
      adrenoceptor desensitization, while endothelial dependent vasodilation of small
      arteries is impaired in CHF. ACE inhibition does not modify the response to
      adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and
      vascular remodeling, which probably contribute to the effect ACE inhibitors have
      on exercise tolerance and survival.

PMID- 9243256
TI  - Effect of efonidipine, a novel dihydropyridine derivative, on myocardial
      metabolic changes induced by coronary artery ligation in dogs: comparison with
      nifedipine.
AB  - Efonidipine is a dihydropyridine derivative having a vasodilating action, which
      is slower in onset and longer in duration than that of nifedipine. In the present
      study, we compared the effects of efonidipine with those of nifedipine on the
      ischemic myocardial metabolism in anesthetized dogs. The heart was made ischemic
      by ligating the left anterior descending coronary artery (LAD) completely for 3
      or 30 min. Efonidipine or nifedipine was injected intravenously, 10 or 3 min,
      respectively, before the start of LAD occlusion. Efonidipine (0.01 or 0.03 mg/kg)
      decreased both blood pressure and heart rate, whereas nifedipine (0.003 mg/kg)
      decreased blood pressure and increased heart rate. The magnitude of decrease in
      mean blood pressure induced by 0.03 mg/kg efonidipine was similar to that induced
      by 0.003 mg/kg nifedipine. Although efonidipine did not modify the changes in
      myocardial carbohydrate metabolism induced by ischemia, it attenuated the
      ischemia-induced decrease in the myocardial level of adenosine triphosphate and
      energy charge potential. Nifedipine, however, did not modify the changes in both
      myocardial energy and carbohydrate metabolism induced by ischemia. The results
      suggest that efonidipine has a cardioprotective effect in the dog, probably
      because of its negative chronotropic effect.

PMID- 9243257
TI  - Chronic inhibition of NO synthase enhances the production of prostacyclin in
      coronary arteries through upregulation of the cyclooxygenase type 1 isoform.
AB  - We previously reported that chronic inhibition of NO synthase (NOS) in dogs leads
      to an upregulation of the cyclooxygenase (COX) pathway in the endothelium of the
      coronary artery after stimulation by bradykinin (BK) in vitro. The present
      experiments were designed to identify the nature of the COX isoform involved in
      this phenomenon. Rings of circumflex (LCX) and left anterior descending (LAD)
      coronary arteries were isolated from six control dogs and six dogs treated with
      the NOS-inhibitor, N omega-nitro-L-arginine (L-NNA, 30 mg/kg/d, i.v., during 7
      days). Concentration-response curves to BK in U46619-contracted rings from LCX
      coronary arteries were constructed in the presence and absence of another NOS
      inhibitor (NG-monomethyl-L-arginine, L-NMMA), of selective inhibitors of the
      inducible isoform of COX (NS-398 and L-745,337) and of a non selective inhibitor
      of the inducible and constitutive isoforms of COX (indomethacin). Finally,
      measurements of 6-keto-prostaglandin F1 alpha, the stable metabolite of
      prostacyclin, were performed in the incubation medium by enzymo-immuno-assay on
      rings of isolated LAD coronary arteries in the presence and absence of the same
      inhibitors of COX, before and after stimulation by BK. In rings taken from
      control dogs, BK evoked a concentration-dependent relaxation (Emax: 115 +/- 10%;
      EC50: 8 +/- 4 nM). In the presence of L-NMMA, the concentration-relaxation curve
      to BK was significantly shifted to the right (Emax: 77 +/- 8%; EC50: 43 +/- 22
      nM, P < 0.05). Addition of NS-398, L-745,337 and indomethacin to L-NMMA did not
      further modify the concentration-relaxation curve to BK. After chronic inhibition
      of NOS, the concentration-relaxation curve to BK was similar to that observed in
      rings taken from control dogs in the presence of L-NMMA (Emax: 75 +/- 5%; EC50:
      69 +/- 36 nM). Addition of L-NMMA, alone or in combination with NS-398 or L
      745,337 did not significantly modify this concentration-relaxation curve to BK.
      In contrast, the L-NMMA-indomethacin combination blunted the BK-induced
      relaxation of the coronary artery (Emax: 28 +/- 10%, P < 0.01). Basal release of
      prostacyclin was not different in rings taken from control and L-NNA treated dogs
      (56 +/- 16 vs 58 +/- 15 pg.mm-2). BK significantly increased this release but the
      increment was twofold greater in rings taken from L-NNA treated dogs than in
      rings taken from control dogs (P < 0.05). In rings taken from control and L-NNA
      treated dogs, the BK-stimulated production of prostacyclin observed in the
      presence of the solvent was not significantly modified by L-NMMA or the L-NMMA-L
      745,337 combination. In contrast, the L-NMMA-indomethacin combination as well as
      endothelium removal completely suppressed the BK-stimulated production of
      prostacyclin. These findings demonstrate that in dogs submitted to chronic
      inhibition of NO synthesis (1) the residual relaxation to BK of canine isolated
      coronary arteries is mainly due to production of prostacyclin of endothelial
      origin, and (2) the enhancement of prostacyclin production by these vessels is
      mainly due to an upregulation of the endothelial constitutive isoform of COX.

PMID- 9243258
TI  - Tachykinin antagonist FK224 inhibits neurokinin A-, substance P- and capsaicin
      induced human bronchial contraction.
AB  - To determine the roles of endogenously released tachykinins (substance P [SP] and
      neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of
      tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP,
      NKA and capsaicin in an organ bath. FK224 (10(-6) M and 10(-5) M, respectively)
      significantly inhibited NKA-induced contraction and 10(-5) M FK224 shifted the
      dose-response curve to more than one log unit higher concentration. Because SP-
      and capsaicin-induced contractions were small, we pretreated the tissues with the
      neutral endopeptidase inhibitor phosphoramidon (10(-5) M), which inhibits
      degradation of exogenous tachykinins in order to potentiate the contractions.
      FK224 (10(-5) M) significantly inhibited SP-induced contraction and it shifted
      the dose-response curves to about one log unit higher concentration. FK224 (10(
      5) M) also significantly inhibited capsaicin-induced contraction and it shifted
      the dose-response curves to more than one log unit higher concentration. In
      contrast, FK224 (10(-5) M) did not affect on acetylcholine-, histamine-, and
      leukotriene D4-induced contraction. These results suggest that FK224 is a
      tachykinin receptor antagonist in the human bronchial smooth muscle, and that
      capsaicin-induced contraction is due to endogenously released tachykinin-like
      substances in the human bronchus.

PMID- 9243259
TI  - Metabolism of clozapine by human neutrophils: evidence for a specific oxidation
      of clozapine by the myeloperoxidase system with inhibition of enzymatic
      chlorination cycle.
AB  - The use of clozapine, an unique antipsychotic drug, raises the real problem of
      drug-induced polymorphonuclear neutrophil cytotoxicity. Clozapine prescription
      has been restricted due to a 1-2% incidence of drug-induced agranulocytosis. The
      exact mechanism of this adverse effect is not yet known. The myeloperoxidase
      hydrogen peroxide system could play a key role in the initiation of
      agranulocytosis. Therefore, we have investigated the clozapine effects on
      hydrogen peroxide and hypochlorous acid, evaluated the peroxidase-mediated
      metabolism of clozapine by mass spectrometry analysis because myeloperoxidase
      uses hydrogen peroxide and chloride producing hypochlorous acid in its
      chlorination cycle, and thus could oxidise clozapine in its peroxidation cycle.
      First, evidence for inhibition of hypochlorous acid production and scavenging of
      hydrogen peroxide by clozapine were demonstrated in vitro, in different cell-free
      and cellular systems. Results are consistent with an inhibition of the
      myeloperoxidase chlorination cycle when clozapine is oxidised in the peroxidation
      cycle. Secondly, ion-spray mass spectrometry analysis allowed us to confirm
      clozapine oxidation by the myeloperoxidase system. Actually, clozapine N-oxide
      with a m/z at 343 was formed. It could be the final step of the metabolisation of
      clozapine via two successive univalent oxidations mediated by peroxidase. We
      suggest that generation of a free cation radical, CLZ(o+), was the initial step.
      CLZ(o+) is a very reactive species and may play an important role in the onset of
      agranulocytosis either by direct toxicity or via an immunological mechanism.
      However, this assumption does not exclude the possible role of other metabolic
      ways involving, in particular, N-desmethylclozapine.

PMID- 9243261
TI  - Clinical trial registries and ethics review boards: the results of a survey by
      the FICHTRE project.
AB  - Clinical trial registries could make an important contribution to research by
      playing a role in the avoidance of trial duplication as well as serving as a
      source of information on the existence of clinical trials for those wishing to
      perform overviews. In order to fulfil their role efficiently, these registries
      should contain information about all trials. However, resources of existing
      registries are not exhaustive. Currently, all protocols for clinical trials must
      be submitted to an ethics review board for approval-thus these boards could
      provide an invaluable source of information about what trials are being
      performed. One of the objectives of our project was to assess the attitudes of
      the ethics review boards (ERBs) to providing this type of information to clinical
      trial registries. We received 115 replies from 281 questionnaires sent to ERBs in
      seven European countries. More than 70% replied that they would be willing to
      communicate information about the trials they review, and there seemed to be
      general agreement that clinical trial registries should be funded and supported
      by governments. Although ERBs could provide a useful source of information, only
      an official body such as the Ministry of Health or a drug regulatory body could
      establish and run a clinical trials registry efficiently.

PMID- 9243260
TI  - Clinical electrophysiologic effects of a single high oral dose of amiodarone.
AB  - Several recent reports have described the antiarrhythmic effects of a single high
      oral dose of amiodarone but clinical electrophysiologic effects have not been
      reported. The present study was performed to assess electrophysiologic effects in
      12 patients. After baseline electrophysiologic studies (EPS) patients were
      administered a single oral dose of 30 mg/kg of amiodarone. EPS was repeated 7.5
      +/- 0.5 hours later. Plasma levels of amiodarone and its metabolite
      desethylamiodarone were determined at the time of the second EPS, Holter
      monitoring was performed for 24 hours after amiodarone administration. Amiodarone
      significantly increased the following parameters: corrected QT interval (+4.5%),
      functional refractory period of the right atrium (+7%); AH interval (+12.3%),
      effective refractory period of the atrioventricular node (+18.5%), and cycle
      length of Wenckebach block (+8.4%). These effects were not correlated with plasma
      levels of amiodarone and desethylamiodarone. Holter monitoring detected no
      significant bradycardia or arrhythmia. These findings indicate that the effects
      of a single high oral dose of amiodarone are the same as those known to be
      induced by acute intravenous administration.

PMID- 9243262
TI  - Comparison of ampicillin/sulbactam versus clindamycin in the prevention of
      infection in patients undergoing head and neck surgery.
AB  - BACKGROUND: Patients requiring major oncologic head and neck surgery are at high
      risk for postoperative wound infection when the surgical site is contaminated by
      secretions from the upper aerodigestive tract. Studies to identify agents active
      in the prevention of postoperative wound infection may serve to reduce patient
      morbidity. METHODS: Patients scheduled for a major contaminated head and neck
      surgical procedure were randomly assigned to receive either ampicillin/sulbactam
      or clindamycin. Medication was administered 1 to 2 hours prior to surgery and
      every 6 hours, for a total of five doses. Postoperatively, patients were followed
      daily for the development of wound infection or other septic complication.
      RESULTS: A total of 242 patients were enrolled in the study; 119 received
      ampicillin/sulbactam, and 123 received clindamycin. A total of 169 patients were
      considered evaluable. Of the evaluable patients, 14% in each group developed a
      postoperative wound infection. There were no statistically significant
      differences between the number of days to onset of wound infection, nor was there
      a statistically significant difference in the rate of non-wound infections in the
      two groups. There were no statistically significant differences between the
      intent to treat group and the evaluable group of patients. CONCLUSION: It is
      concluded that ampicillin/sulbactam is as safe and effective as clindamycin in
      preventing postoperative wound infection following major head and neck surgery.

PMID- 9243263
TI  - Risk factors for pulmonary complications in the postoperative head and neck
      surgery patient.
AB  - BACKGROUND: Pulmonary complications are a primary source of increased cost and
      morbidity in surgically treated head and neck cancer patients. This study
      investigates potential risk factors related to postoperative pulmonary
      complications (pneumonia, adult respiratory distress syndrome (ARDS), and
      prolonged mechanical ventilation) in head and neck cancer patients. METHODS: Data
      from 144 major head and neck procedures performed at the University of Washington
      between 1985 and 1991 were retrospectively reviewed. Univariate and multivariate
      analysis were used to evaluate preoperative and perioperative variables
      identified as potential risk factors for postoperative pulmonary complications.
      RESULTS: Fifteen percent of patients had a postoperative pulmonary complication,
      (n = 21: 18 postoperative pneumonia; 2 ARDS; and 4 prolonged ventilation). The
      most common pneumonia pathogen was Staphylococcus aureus (62%). Univariate
      analysis identified smoking and weight loss as significant factors associated
      with pulmonary complications. The variables preoperative blood urea nitrogen,
      white blood cell count, and operative chest flap closure all approached but did
      not reach significance. Multivariate analysis of a subgroup of patients
      identified smoking history and perioperative antibiotic choice as the only
      independently significant variables. CONCLUSIONS: Patient smoking history was the
      primary variable related to postoperative pulmonary problems, with evidence of
      increasing risk with increased exposure. Other variables added only limited
      additional risk association information after multivariate analysis.

PMID- 9243264
TI  - Total thyroidectomy for Graves' disease.
AB  - BACKGROUND: Therapeutic options for treatment of hyperthyroidism caused by
      Graves' disease remain controversial. There are three main options: thiourea
      drugs, radioactive iodine ablation, and thyroidectomy. Each treatment has
      significant advantages and potential problems. METHODS: The present study is a
      retrospective analysis of our experience with total thyroidectomy in Graves'
      disease. Sixty-two patients underwent this procedure in 11 years' time and were
      followed for a minimum of 2 years after surgery. All had measurement of total
      thyroxine, T3 uptake, and radioactive iodine (RAI) uptake and scanning. Sixty
      three percent of all patients had some element of hyperthyroid eye signs. All
      patients were rendered euthyroid with pharmacologic therapy prior to surgery.
      Postoperatively, the patients were evaluated for improvement in eye signs,
      incidence of recurrent laryngeal nerve injury, and hypoparathyroidism. RESULTS:
      None of the patients in this study have developed recurrent hyperthyroidism. All
      patients are maintained on levothyroxine. None of our patients incurred bilateral
      vocal cord paralysis. One patient (1.6%) demonstrated an immobile vocal cord more
      than 1 year following surgery. Ten patients (16%) demonstrated impaired mobility
      of one vocal cord in the immediate postoperative period. Nine of these patients
      recovered full vocal cord mobility within 6 months after surgery. Only one
      patient (1.6%) still required calcium and vitamin D therapy 1 year following
      surgery. However, in the immediate postoperative period, 23 patients (37%)
      required supplemental calcium and vitamin D. In 12 patients, calcium and vitamin
      D was discontinued within 1 month. In an additional 6 patients, calcium and
      vitamin D were discontinued within 4 months; 3 patients, within 6 months; and 1
      patient, within 12 months after surgery. Incidental papillary carcinoma was found
      in 3 patients (5%). CONCLUSIONS: Total thyroidectomy for Graves' disease is an
      effective and safe therapy. When performed by an experienced head and neck
      surgeon, it carries a low morbidity rate. It should be presented to patients as a
      therapeutic option within the context of a comprehensive discussion of the risks
      and benefits of radioactive iodine, pharmacologic therapy, and surgery.

PMID- 9243265
TI  - Effects of implantable biomaterials on radiation dosimetry.
AB  - BACKGROUND: It is generally known that radiation dose is enhanced in front of and
      reduced behind metallic plates. This study evaluates metallic, ceramic, and
      bioabsorbable facial-reconstruction materials for their differential effects on
      radiation dosimetry. METHODS: Commercially pure titanium (cpt), stainless steel
      (steel), titanium alloy (tia), hydroxyapatite (HA), and poly-L-lactide (PLA, a
      bioabsorbable polymer) were obtained for this study. The radiation doses distal
      (behind) and proximal (in front of) to the test material were measured with an
      ionization chamber placed at several distances from the test material. Therefore,
      transmission (proximal to plate) and backscattering (distal to plate) factors
      were generated at several distances for each material. RESULTS: Poly-L-lactide
      transmitted nearly 100% of the incident radiation beam. The metals had the
      greatest effect on transmission with steel, followed by cpt, tia, and HA showing
      the greatest reduction of incident beam. Poly-L-lactide revealed minimal
      backscattering. Greater backscatter of the incident radiation beam was seen from
      steel, followed by cpt and HA. Poly-L-lactide also behaved similar to water in
      transmission and backscatters properties during electron irradiation.
      CONCLUSIONS: Poly-L-lactide has a minimal effect on the radiation-dose
      distribution and may be beneficial as a reconstructive device for patients
      undergoing head and neck cancer radiotherapy. Hydroxyapatite showed a relatively
      minor effect, whereas the metals (steel, followed by cpt and tia) revealed the
      greatest detrimental effect on the radiation-dose distribution.

PMID- 9243266
TI  - Nasopharyngeal angiofibromas: selecting a surgical approach.
AB  - BACKGROUND: A review of 16 juvenile nasopharyngeal angiofibromas, managed at the
      University of Pittsburgh, is presented. METHODS: A retrospective chart review was
      done. Surgical approaches and factors affecting recurrence are analyzed. RESULTS:
      Endoscopic transnasal, transpalatal, medial maxillectomy, facial translocation,
      and infratemporal fossa approaches, with or without craniotomy, were employed.
      The 37.5% recurrence rate reflects the advanced stage of the tumors. A major risk
      factor for recurrence was tumor involvement of the cranial base. CONCLUSIONS: The
      surgical approach should be selected according to tumor location and
      effectiveness of embolization. In young patients, the approach should minimize
      the potential for facial growth retardation. Tumors confined to the nasopharynx,
      nasal cavity, and paranasal sinuses may be removed endoscopically. Medial
      maxillectomy is recommended for tumors that extend to the medial intratemporal
      fossa or medial cavernous sinus. Significant involvement of the infratemporal
      fossa, cavernous sinus, or middle cranial fossa requires infratemporal fossa or
      transfacial approaches.

PMID- 9243267
TI  - Squamous cell carcinoma of the floor of mouth: a 20-year review.
AB  - BACKGROUND: This study retrospectively examines our treatment choices and
      outcomes with patients diagnosed with squamous cell cancer of the floor of mouth.
      Because of our division's past strong surgical bias in the treatment of this
      disease, we have assessed the results of a patient population treated largely by
      surgical extirpation. This clinical information has been used to draw conclusions
      and formulate treatment paradigms for patients with floor of mouth cancer.
      METHODS: Four hundred fifty patients with the diagnosis of squamous cell
      carcinoma of the oral cavity received their primary treatment at Roswell Park
      Cancer Center (RPCI) from 1971 to 1991. Ninety-nine had disease originating in
      the floor of mouth and are the basis of this retrospective review. RESULTS: Forty
      three percent of the patients had early-stage disease (stage I or II). Five-year
      survival for stages I through IV was 95%, 86%, 82%, and 52%, respectively. The
      incidence of occult cervical metastases for clinical stage I patients was 21%.
      For clinical stage II patients, the incidence was 62%. Local control of patients
      treated with surgery alone was 81%. The regional control rate for these patients
      was 71%. In patients where negative margins were achieved (> or = 5 mm), the
      local recurrence rate was 13%, regardless of T stage. Eleven percent of the
      patients underwent a course of postoperative radiotherapy; all had stage IV
      disease. When compared with advanced-stage patients undergoing surgery alone,
      there was a significantly improved regional control rate and a trend toward
      enhanced survival in the patients receiving adjuvant radiotherapy. CONCLUSIONS:
      There is a significantly high incidence of occult metastatic disease (21%) for T1
      lesions or greater in floor of mouth cancer to warrant elective treatment of
      regional lymphatics. In patients treated with surgery alone with negative
      margins, the local control rate was 90% versus 62% when the margins were close or
      positive. Adjunctive radiotherapy showed a statistically significant (p = .005)
      increased regional control in patients with stage IV disease. Adjunctive
      radiotherapy is warranted for increased regional control of disease; good local
      control can be achieved in floor of mouth cancer with surgery alone when negative
      margins are obtained.

PMID- 9243268
TI  - Resection and immediate microvascular reconstruction in the management of
      osteoradionecrosis of the mandible.
AB  - BACKGROUND: Management of osteoradionecrosis (ORN) remains a difficult and
      challenging problem. The traditional approach using debridement, antibiotics, and
      occasionally hyperbaric oxygen is usually successful in treating minimal ORN.
      However, when bone and soft-tissue necrosis is extensive, the conservative
      approach usually requires intensive care over a long period of time and often
      yields unsatisfactory functional and cosmetic results. METHODS: Within the past 5
      years, we have used radical resection of the mandible with immediate
      microvascular reconstruction in the treatment of extensive ORN of the mandible.
      This aggressive surgical approach was used in six patients with advanced ORN of
      the mandible, all of whom had failed initial conservative treatment, including
      hyperbaric oxygen therapy in three. A fibular free graft with microvascular
      anastomosis was used in all patients. RESULTS: All the patients healed primarily
      with minimal postoperative morbidity and excellent cosmetic results. Two patients
      subsequently required removal of some of their hardware. One patient had
      placement of osseointegrated implants with an excellent cosmetic and functional
      result. CONCLUSION: Microvascular reconstruction with its own blood supply seems
      to expedite bone healing and limit further osteoradionecrosis of the remaining
      mandible. Although prevention is the primary goal in radiation injury, our
      experience suggests that radical resection with free microvascular reconstruction
      offers significant advantages to selected patients with extensive ORN of the
      mandible.

PMID- 9243269
TI  - Pectoralis major myofascial flap: a valuable tool in contemporary head and neck
      reconstruction.
AB  - BACKGROUND: The pectoralis major myofascial (PMMF) unit is rapidly mobilized,
      reliable, and extremely useful in a number of clinical situations calling for
      vascularized soft-tissue coverage in the head and neck. Although free-tissue
      transfer has emerged as the preferred method of reconstruction for a large
      variety of defects in the head and neck, the pectoralis major muscle should be
      considered when vascularized soft-tissue coverage is required in this area.
      METHODS: A retrospective chart review of 24 PMMF flaps performed at the
      University of Iowa Hospitals and Clinics between January 1, 1991, and May 1,
      1996, was undertaken. Outcomes were evaluated relative to accomplishing the
      established preoperative surgical goals. RESULTS: Utilization of the PMMF flap
      was grouped according to four primary indications: (1) protection of threatened
      great vessels or free flap vascular pedicles in situations of wound breakdown due
      to fistula or infection (7 cases); (2) vascularized soft-tissue coverage of great
      vessels or free-flap vascular pedicles and prevention of potential wound
      breakdown in surgical defects in which compromised healing was anticipated (7
      cases); (3) closure of small pharyngeal defects (2 cases); or (4) vascularized
      coverage of the mandible following debridement for osteoradionecrosis (8 cases).
      The PMMF flap was 100% successful when the surgical goal was to protect exposed
      vascular structures and promote wound healing in the presence of fistula or
      infection. The PMMF flap was 100% successful in the protection of vascular
      structures and prevention of wound breakdown in cases where compromised wound
      healing was anticipated. The PMMF flap provided closure, and a vascularized
      surface for mucosalization, when used to primarily reconstruct small pharyngeal
      defects. The PMMF flap provided definitive closure in 5 of 8 (62.5%) cases of
      osteoradionecrosis of the mandible when it was used to invest the remaining
      mandibular bone. Three of 8 cases (37.5%) required further surgical management
      and were considered failures. An acceptable cosmetic outcome was obtained in
      women undergoing this procedure by using an inframammary incision. The
      preoperative goal of the PMMF flap procedure was met in 21 of 24 (87.5%) cases.
      There was a major complication rate of 12.5% as well as a minor complication rate
      of 12.5%. CONCLUSION: In cases requiring the protection of vital vascular
      structures from infection, salivary secretions or skin flap breakdown, the PMMF
      flap should be considered. The PMMF flap is an excellent reconstructive option in
      selected clinical situations, where vascularized soft-tissue coverage is required
      in the head and neck.

PMID- 9243270
TI  - Assessment of malnutrition parameters in head and neck cancer and their relation
      to postoperative complications.
AB  - BACKGROUND: Malnutrition is reported frequently in head and neck cancer patients.
      The impact of malnutrition on surgical outcome is not clearly understood. The
      purpose of this study was to define the usefulness of six different parameters in
      scoring malnutrition and to determine the nutritional parameter primarily related
      to postoperative complications. METHODS: Sixty-four patients undergoing major
      surgery for advanced head and neck cancer were studied prospectively, and six
      different parameters were used to define malnutrition. Logistic regression was
      used to relate nutritional parameters to postoperative complications. RESULTS:
      The parameters applied all identified different aspects of the nutritional
      status, as malnutrition varied between 20% and 67%. Logistic regression analysis
      identified a weight loss of more than 10% to be the most prominent predictive
      parameter for the occurrence of major postoperative complications. CONCLUSIONS:
      Patients with weight loss more than 10% during the six months before surgery are
      at a great risk for the occurrence of major postoperative complications.

PMID- 9243271
TI  - Timing of edentulation and extraction in the management of oral cavity and
      oropharyngeal malignancies.
AB  - BACKGROUND: Pretreatment dental evaluation is an essential element in the
      management of the head and neck cancer patient. Frequently, the dental condition
      requires edentulation or multiple extractions prior to radiotherapy. These
      extractions may be carried out at the time of oncologic resection. Such practice
      is routine for some surgeons but resisted by others who fear increased
      postoperative wound complications. To date, no study evaluating the safety and
      efficacy of extractions at the time of surgical resection has been reported. This
      paper retrospectively examines the postoperative course of head and neck cancer
      patients with varying strategies of dental management. METHODS: Retrospective
      analysis of patients with surgically treated oral cavity or oropharyngeal
      malignancies and dental extractions or edentulation at a tertiary oncology center
      from 1985 to 1994 was made. Postoperative wound infection, fistula, and length of
      stay data were compared for patients undergoing concurrent extraction and those
      having dental extractions in the postoperative period. RESULTS: Thirty-two
      patients underwent ablative resection with concurrent extraction, whereas 23 had
      postsurgical extractions. The infection and fistula rates were 16% and 9% in the
      concurrent group and 35% and 26% for patients having postsurgical extractions.
      Mean postoperative stays were significantly shorter for patients undergoing
      concurrent extraction (15 +/- 8 days) compared with those of the postsurgical
      group (27 +/- 14 days). CONCLUSIONS: Patients whose extractions were performed
      concurrent with the oncologic resection experienced fewer postoperative wound
      complications and had significantly shorter postoperative hospitalizations than
      did the postsurgical group.

PMID- 9243272
TI  - Mucoepidermoid carcinoma in a 10-year-old girl.

PMID- 9243273
TI  - Carcinoma arising in a dentigerous cyst with neck metastasis.
AB  - BACKGROUND: Squamous cell carcinoma arising in a dentigerous cyst is extremely
      uncommon. The diagnosis of carcinoma arising in a dentigerous cyst requires
      microscopically that an area of benign cystic epithelium is observed to
      transition into squamous cell carcinoma. In the present case, the patient was
      diagnosed with squamous cell carcinoma of the neck with an unknown primary. The
      primary site was found to be the follicular space associated with the right
      mandibular third molar. METHODS: Light microscopic studies were performed to
      arrive at the final diagnosis. RESULTS: Transition of the epithelial lining of
      the dentigerous cyst to squamous cell carcinoma was observed in multiple fields.
      CONCLUSIONS: The present case demonstrates that odontogenic cysts have to be
      considered a possible source of metastatic disease.

PMID- 9243274
TI  - Subglottic nerve sheath tumor in a pediatric patient: case report and literature
      review.
AB  - BACKGROUND: Although nerve sheath tumors (neurilemmoma and neurofibroma) can
      occur on any nerve with Schwann cells, laryngeal involvement is very uncommon.
      The vast majority of reported laryngeal nerve sheath tumors have been located in
      the supraglottic area. Our case report involves the diagnosis and management of a
      subglottic nerve sheath tumor in a pediatric patient. Only two previous reports
      of such a lesion appear in the world literature. METHODS: A 12-year-old girl was
      initially seen by her allergist for evaluation of a 2-month history of wheezing
      and nocturnal dyspnea. Therapy with bronchodilators and steroids had limited
      success. Flow-volume loop studies suggested a fixed upper airway obstruction, and
      an office laryngoscopy identified a cherry red, submucosal subglottic lesion.
      Magnetic resonance imaging (MRI) scan verified the presence of a smooth,
      homogeneous subglottic mass. RESULTS: An endoscopic CO2 laser excision of the
      lesion was performed using jet ventilation technique. Histopathology determined
      the lesion to be a nerve sheath tumor (neurilemmoma versus neurofibroma).
      Postoperatively, the patient has been asymptomatic without evidence of
      recurrence. CONCLUSIONS: A subglottic nerve sheath tumor in a pediatric patient
      is very rare. Although endoscopic and open approaches have been advocated, CO2
      laser with jet ventilation provided an excellent modality for resecting this
      lesion.

PMID- 9243275
TI  - Frequency and therapeutic implications of "skip metastases" in the neck from
      squamous carcinoma of the oral tongue.

PMID- 9243276
TI  - Type X collagen expression and hypertrophic differentiation in chondrogenic
      neoplasias.
AB  - Little is known about matrix biochemistry and cell differentiation patterns in
      chondrogenic neoplasms. This is the first description of the focal expression of
      collagen type X by neoplastic chondrocytes in situ and its incorporation into the
      extracellular matrix of cartilaginous tumors. This shows that neoplastic
      chondrocytes have the potential to undergo the full program of cell
      differentiation, including hypertrophy, comparable to their physiological
      counterparts in the growth plate. However, only in benign osteochondromas was a
      zonal expression of type X collagen found similar to that observed in the growth
      plate, where the cells immediately above the ossification frontier are
      selectively positive for type X collagen. In enchondromas and chondrosarcomas,
      the expression was randomly distributed within the tumors. Surprisingly, in less
      differentiated chondrosarcomas with spindle-shaped cells and non-cartilaginous
      extracellular matrix, exceptional expression of collagen type X was observed,
      which indicates potential uncoupling of collagen type X expression from the
      differentiated chondrocytic phenotype in neoplastic chondrocytes in vivo.

PMID- 9243277
TI  - Localization of membrane-associated sialomucin on the free surface of mesothelial
      cells of the pleura, pericardium, and peritoneum.
AB  - Strong anionic sites, as recognized by deposition of cationic colloidal iron even
      at pH 1.5, were distributed on the free surfaces of the mesothelia of the mouse
      pleura, pericardium, and peritoneum. Methylation inhibited colloidal iron
      staining on the surface, and successive saponification restored it. Digestion
      with neuraminidase or hydrolysis of sialic acid with H2SO4 erased the colloidal
      iron staining. Lectin Limax flavus agglutinin (LFA), which is specific for sialic
      acid, labeled the free surface of the mesothelium. All these findings strongly
      suggested that the surface substance contained sialic acid. Moreover, prior
      treatment with LFA inhibited the mesothelial surface stain with colloidal iron.
      In transmission electron microscopy, the colloidal iron (pH 7.3)-stained
      substance took the shape of fine strands of 50-300 nm in length. These
      characteristics of the substance on the mesothelial surface correspond well with
      biochemical properties of membrane-associated sialomucin, whose strong and
      abundant negative charges produce repulsive forces between facing serosal
      surfaces. This may contribute to prevent serosal adhesion and to reduce friction
      during movements of organs.

PMID- 9243278
TI  - Immunocytochemical localisation of neuronal nitric oxide synthase in developing
      and transplanted rabbit retinas.
AB  - Nitric oxide (NO) acts as a modulator of neuronal transmission in mature neuronal
      systems, including the retina. Recently, NO has also been suggested to have a
      trophic function during development. We examined immunocytochemically the
      distribution of NO-producing cells in developing and transplanted rabbit retinas.
      An antibody detecting the neuronal isoform of its biosynthetic enzyme, nitric
      oxide synthase (NOS), was used on normal developing retinas [starting at
      embryonic day (E) 15] and on rabbit retinal transplants after various survival
      times (1-139 days after surgery). Weakly stained cell bodies were first observed
      in the proximal margin of the neuroblastic layer at E 29. Stained processes
      projecting towards a developing inner plexiform layer were also visible at this
      time point. Immunoreactive cells were located at later stages in the innermost
      part of the inner nuclear layer and in the ganglion cell layer, and are likely to
      correspond mainly to amacrine cells. NOS-labelled cells were also found in
      retinal transplants. The first NOS-labelled cells appeared, as in normal
      developing retinas, in ages corresponding to E 29 and were still detected in
      transplants corresponding to postnatal day 123. NOS-labelled cells were seen in
      areas between rosettes, where amacrine cells are located. NOS-labelled processes
      were at times seen to project for long distances, forming very distinct plexuses.
      NOS-containing amacrine cells thus appear both in the transplants and in
      developing retinas in the embryonic stages, long before synaptic function
      involving these cells can be expected, suggesting a role for NO not only in
      neuromodulation but also in retinal development.

PMID- 9243279
TI  - Origin of the central cells of erythroblastic islands in fetal mouse liver:
      ultrahistochemical studies of membrane-bound glycoconjugates.
AB  - To clarify the origin of the central cells in hepatic erythroblastic islands,
      glycoconjugates on the surface of cellular constituents in fetal mice liver were
      ultrahistochemically examined using lectin staining. At 11 days of gestation, the
      cells derived from mesenchyme in fetal liver, including sinusoidal macrophages,
      endothelial cells, and erythropoietic cells, bound Griffonia simplicifolia
      isoagglutinin I-B4 (GS-I-B4), but hepatocytes lacked binding sites for the
      isolectin. Scavenger macrophages in the hepatic cords at 13 days of gestation and
      the central cells in the erythroblastic islands at 15 days of gestation also
      bound GS-I-B4. Hepatocytes, however, exhibited no GS-I-B4 binding site at any
      gestational day. At 11 days of gestation, none of the cells in fetal liver had
      binding sites for soybean agglutinin (SBA), but cells derived from mesenchyme
      acquired these binding sites at 13 days of gestation. The central cells in the
      erythroblastic islands also bound SBA, but hepatocytes did not bind the lectin at
      all. The central cells in the erythroblastic islands can be considered to belong
      to a mesenchymal cell lineage, and primitive sinusoidal macrophages at 11 days of
      gestation are possible precursors of these central cells.

PMID- 9243280
TI  - Immunocytochemical and quantitative study of the tunica albuginea testis in young
      and ageing men.
AB  - A light and electron microscope immunohistochemical study of the tunica albuginea
      from both young and elderly men was carried out to determine the distribution of
      the cells that contain actin, vimentin and/or desmin, and to evaluate the
      possible variations with ageing by means of quantitative studies. Testicular
      volume and testicular parenchyma volume decreased significantly with age whereas
      the tunica albuginea volume remained unchanged. These results agree with the
      scanty quantitative changes observed in the testicular connective tissue with
      age, and the notion that age-related changes in testicular volume are principally
      restricted to the seminiferous tubules. Three connective tissue layers could be
      distinguished in the tunica albuginea in both young and elderly men. The middle
      and inner layers increased in width with age while the width of the outer layer
      decreased. The average width of the tunica albuginea increased significantly with
      ageing. The tunica albuginea of young men and elderly men presented two types of
      fusiform cells: (1) fibroblast-like cells, which immunoreacted to actin and
      vimentin, but not to desmin; and (2) myoid cells, which immunoreacted to actin,
      vimentin and desmin. In both young men and elderly men, the total number of
      desmin-positive cells (myoid cells) was significantly lower than that of
      fibroblasts. However, the total number of desmin-positive cells was significantly
      increased in ageing men. In young testes, desmin-positive cells were more
      abundant in the outer layer of the tunica albuginea, whereas in elderly men these
      cells predominated in the middle layer. The increased desmin immunoexpression in
      the tunica albuginea of ageing men contrasts with the decrease in desmin
      immunoreaction in other myoid cells of the testis, the peritubular myoid cells,
      but only in seminiferous tubules that showed severe germ cell depletion. This
      suggests that changes in intermediate filament immunoexpression in peritubular
      cells are focalised, and thus, under local control, whereas changes in the tunica
      albuginea cells are generalised and possibly related to factors also affecting
      the connective tissue in other organs.

PMID- 9243281
TI  - The specific expression of tenascin in the synovial membrane of the
      temporomandibular joint with internal derangement: an immunohistochemical study.
AB  - The expression of tenascin (TN) in the tempormandibular joint (TMJ) disc and
      synovial membrane was examined in 18 human TMJ samples from patients with
      internal derangement of the TMJ and ten control specimens by an
      immunohistological technique using paraffin-embedded tissue and specific anti
      human TN monoclonal antibody (RCB-1). The expression of TN was observed in all 28
      samples, but it was limited to the walls of blood vessels, the perineurium, and
      the surface of the TMJ disc. The expression of TN was diffuse in the stroma of
      mildly hypertrophic synovial membranes and focal in the surface of severely
      hypertrophic synovial membranes. The clinical symptoms of internal derangement of
      the TMJ are thought to be related to the degree of synovitis. The present study
      demonstrates that TN is expressed specifically in the portion of the TMJ synovial
      membrane affected with internal derangement.

PMID- 9243282
TI  - Immunochemical and immunohistochemical study of the 27- and 29-kDa calcium
      binding proteins and related proteins in the porcine tooth germ.
AB  - Our previous report identified 27- and 29-kDa calcium-binding proteins in porcine
      immature dental enamel. In this study we revealed that the N-terminal amino acid
      sequences of the two proteins were identical: LLANPXGXIPNLARGPAGRSRGPPG. The
      sequence matches a portion of the amino acid sequence of the porcine sheath
      protein, sheathlin. Porcine tooth germs were investigated immunochemically and
      immunohistochemically using specific antibodies raised against synthetic peptide
      that included residues 13-25 of this sequence. The affinity-purified antibodies
      reacted with several proteins extracted from newly formed immature enamel in
      immunochemical analyses, especially protein bands migrating at 62, 35-45, 29, and
      27 kDa in SDS-polyacrylamide gels. The largest protein detected was a weak band
      near 70 kDa. In immunochemical analyses of proteins extracted from the inner
      (old) immature enamel, the antibody reacted faintly with the 27- and 29-kDa
      proteins. In immunohistochemical preparations, the Golgi apparatus and secretory
      granules of the secretory ameloblast, and the surface layer of immature enamel
      showed immunoreactivity. The immunoreactivity of immature enamel just beneath the
      secretory face of the Tomes' process was intense. No immunoreactivity was found
      in the Golgi apparatus of the maturation ameloblast. These results suggest that
      the 70-kDa protein, whose degradation might be very fast, is the parent protein
      of the 27- and 29-kDa proteins.

PMID- 9243283
TI  - Immunohistochemical evidence for the existence of rat cytosolic sialidase in rat
      skeletal muscles.
AB  - Histochemical evidence is required to demonstrate the presence of biochemically
      defined cytosolic sialidase. To meet this requirement, we examined the
      immunohistochemical localization of the enzyme in rat skeletal muscles. Sections
      of chemically fixed tissues were incubated with a polyclonal antibody raised
      against a synthetic peptide which corresponded to a part of the enzyme protein.
      After incubation with the primary antibody, cryosections for fluorescence
      microscopy and resin sections for electron microscopy were incubated with a
      fluorochrome- and colloidal gold-labeled secondary antibody, respectively.
      Immunofluorescence was diffusely distributed in the muscle fibers and was also
      found in the perimysium and blood vessels. Many immunogold particles were
      scattered over the sarcoplasm, myofibrils, nucleoplasm, and matrix of
      mitochondria. The immunogold particles were also found in the equivalent
      compartments of axons, Schwann cells, and cells of endomysium and blood vessels.
      The specificity of the primary antibody was elucidated by immunoblotting and an
      immunoprecipitation test. These findings clearly indicate that this type of
      sialidase is essentially located in the cytosolic compartment. Consequently, the
      name, cytosolic sialidase, will be appropriate for this enzyme. Additionally it
      is indicated that this enzyme is also present in cells other than skeletal muscle
      fibers.

PMID- 9243284
TI  - A- and B-type lamins are differentially expressed in normal human tissues.
AB  - A selection of normal human tissues was investigated for the presence of lamins
      B1, B2, and A-type lamins, using a panel of antibodies specific for the
      individual lamin subtypes. By use of immunoprecipitation and two-dimensional
      immunoblotting techniques we demonstrated that these antibodies do not cross
      react with other lamin subtypes and that a range of different phosphorylation
      isoforms is recognized by each antibody. The lamin B2 antibodies appeared to
      decorate the nuclear lamina in all tissues examined, except hepatocytes, in which
      very little lamin B2 expression was observed. In contrast to previous studies,
      which suggested the ubiquitous expression of lamin B1 in mammalian tissues, we
      show that lamin B1 is not as universally distributed throughout normal human
      tissues as was to be expected from previous studies. Muscle and connective
      tissues are negative, while in epithelial cells lamin B1 seemed to be
      preferentially detected in proliferating cells. These results correspond well
      with those obtained for lamin B1 in chicken tissues. The expression of A-type
      lamins is most prominent in well-differentiated epithelial cells. Relatively
      undifferentiated and proliferating cells in epithelia showed a clearly reduced
      expression of A-type lamins. Furthermore, most cells of neuroendocrine origin as
      well as most hematopoietic cells were negative for A-type lamin antibodies.

PMID- 9243285
TI  - Combination of non-isotopic in situ hybridisation with detection of enzyme
      activity, bromodeoxyuridine incorporation and immunohistochemical markers.
AB  - The advent of non-isotopic in situ hybridisation allows the possibility to detect
      the presence of both mRNAs and other markers in cells. We have established
      conditions for simultaneous analysis of gene expression and a variety of other
      immunohistochemical markers in tissue sections. We report the analysis of
      expression of a family of transcription factors (Sox genes) in combination with
      detection of: (1) protein antigens (using both monoclonal and polyclonal
      antibodies); (2) bromodeoxyuridine to mark cells which are proliferating; and (3)
      acetylcholinesterase activity. The approaches we describe, which demonstrate the
      compatibility of non-isotopic in situ hybridisation with a range of other
      treatments, should be generally applicable and open to many variations of probe,
      antibodies and colour detection systems.

PMID- 9243286
TI  - The role of dendritic cells in T cell activation.
AB  - Dendritic cells (DC) are distinguishable from other antigen-presenting cells by
      their potent antigen-presenting capacity. They are not only efficient at
      presenting peptide antigen but can also process and present soluble protein
      antigen sto antigen-specific T cells and cloned T cell lines. They are very
      strong stimulators of both allogeneic and syngeneic mixed lymphocyte reactions
      and have a unique capacity to stimulate naive T cells. The potent functional
      capacity of DC is related to a high-level expression of major histocompatibility
      complex class I/II molecules and constitutive expression of costimulatory
      molecules, such as CD80/CD86, as well as heat stable antigen, CD40 and the
      leucocyte function antigen (LFA) family of adhesion molecules. Recent studies
      have shown that DC are also involved in regulation of the immune response via
      induction of both central and peripheral tolerance.

PMID- 9243287
TI  - Elution and partial characterization of immunoglobulins bound to ovine placenta.
AB  - Immunoglobulins were eluted from ovine placentae and characterized by
      immunoprecipitation, electrophoresis, western blotting and ELISA. IgG was shown
      to comprise the bulk of placental-bound immunoglobulins while smaller amounts of
      IgM and only trace amounts of IgA were demonstrated. Results suggest that ovine
      placental IgG eluted by surgical cannulation of the uterine blood vessels in situ
      is similar to that eluted from postpartum placentae in vitro, implying that there
      may be some transfer of antibodies across the maternal side of the placental
      barrier to the trophoblast. These antibodies are rich in IgG1 and IgG2, have a
      relative molecular weight of 158 kDa, and bind to an 80 kDa peptide prepared from
      pre-acidified ovine placental cotyledons. We propose that the binding of
      placental IgG to the 80 kDa antigen may prevent immunological rejection of the
      foetus by competitively excluding cytotoxic cells of maternal origin such as NK
      cells. Also, given that a similar antigen (80 kDa) has been reported in humans
      and equines, and shown to be saturated with IgG in term placentae, we propose
      that this antigen may be conserved in several mammalian species for reproductive
      purpose. Consequently, we suggest that the ovine placental IgG and the 80 kDa
      antigen may be suitable as models for the study of maternal-foetal interactions
      in mammalian pregnancies.

PMID- 9243288
TI  - Down-regulation of an established immune response via chemical carcinogen or UVB
      altered skin.
AB  - The ability to produce antigen-specific down-regulation of an established immune
      response was investigated in 2,4,6-trinitrochlorobenzene (TNCB)-immune mice by
      delivery of antigen through chemical carcinogen- or ultraviolet B (UVB)-treated
      skin. When TNCB-immune mice were treated on the dorsal trunk skin with 7,12
      dimethylbenz(a)anthracene (DMBA) followed by TNCB there was an antigen-specific
      reduction in both contact sensitivity and antibody production. Further, immune
      mice that received spleen cells from naive syngeneic donors treated with DMBA
      followed by TNCB also exhibited a reduction in both contact sensitivity and
      antibody production. In contrast, mice treated with UVB irradiation followed by
      TNCB had a reduction in contact sensitivity but not antibody production. These
      results provide evidence that an ongoing immune response can be manipulated by
      immunization through a modified skin immune system. This may provide a beneficial
      approach for the treatment of autoimmune disease.

PMID- 9243289
TI  - B cell responses to a peptide epitope. II: Multiple levels of selection during
      maturation of primary responses.
AB  - This report analyses murine primary humoral recognition of a linear domain (MEP
      17-31) within a 100 amino acid polypeptide, MEP-1. An analysis of the early
      primary IgM response revealed that MEP 17-31 presented at least two distinct
      domains for pre-immune B cell recognition represented by MEP-1 residues 19-23 and
      26-28. However, subsequent maturation into an IgG response saw an exclusive
      selection for the anti-MEP 19-23 component with loss of all alternate
      specificities. The IgM response to MEP 19-23 was oligoclonal and composed of
      diverse paratope phenotypes as evidenced by varied heavy chains of immunoglobulin
      V-D-J combinations and CDR3 sequences. In contrast to the oligoclonality of IgM
      mAb, the mature IgG response to MEP 19-23 appeared to derive predominantly from a
      single progenitor. It therefore appears that maturation of primary humoral
      responses to polypeptide antigens involves two distinct levels of selection.
      While there is selection for a restricted subset of the initially induced
      antibody fine-specificities, progression of the response also entails a reduction
      in clonal heterogeneity of B cells responding to the dominant epitope.

PMID- 9243290
TI  - Tumour eradication with high-dose idarubicin-anti-Ly-2.1 with murine tumour
      necrosis factor-alpha in mice.
AB  - The antitumour efficacy of Ida-anti-Ly-2.1 immunoconjugate in combination with
      murine TNF-alpha (mTNF-alpha) has been evaluated in a disseminated murine thymic
      lymphoma model E3. This tumour model shows characteristics similar to lymphoma in
      humans with widely disseminated tumour in major organs. In vitro both idarubicin
      (Ida) and Ida-anti-Ly-2.1 showed additive and synergistic cytotoxic effects,
      respectively, with mTNF-alpha when tested using the isobolagram method. Similar
      synergistic effects were also seen in vivo. Tumour-bearing mice were treated with
      various doses of mTNF-alpha and Ida alone, however, neither showed a therapeutic
      response in mice. When mice were treated with Ida-anti-Ly-2.1 'early' the median
      survival time (MST) was increased by 8 days, however, 'late' treatment was
      ineffective. Combination therapy of mTNF-alpha and Ida-anti-Ly-2.1 conjugate (42
      micrograms) given 'early' was capable of curing 50% of mice. However, when tumour
      bearing mice were given a high dose (234 micrograms) of Ida-anti-Ly-2.1 together
      with mTNF-alpha 100% of mice survived disease free. Such an effect was not
      observed when free mTNF-alpha, Ida-anti-Ly-2.1, anti-Ly-2.1 or a mixture of anti
      Ly-2.1+mTNF-alpha was given at the same dose. These results show that a
      combination of very toxic drug immunoconjugates and TNF could lead to the
      eradication of disseminated tumour in mice and may be relevant for the treatment
      of minimal residual disease in cancer patients.

PMID- 9243292
TI  - Murine monoclonal IgG antibodies: differences in their IgG isotypes can affect
      the antibody effector activity when using human cells.
AB  - The current studies were aimed at investigating why certain murine anti-CD3
      isotypes (e.g. IgG2b) were poor activators of human T cells despite binding to
      the same epitope as the IgG2a anti-CD3. Most experiments were conducted with a
      human T cell line (HuT-78) and U937 a human histiocytic cell line with Fc gamma
      RI and Fc gamma RII. HuT-78 cells lack Fc gamma R. Anti-CD3-TCR of IgG2a isotypes
      and some antibodies of the IgG1 isotype, but not IgG2b, activated HuT-78 to
      secrete IL-2 only in the presence of U937. Epitope binding differences could not
      entirely explain these observations as OKT3E(IgG2a) but not its switch variant
      (IgG2b) activated HuT-78 in the presence of U937. Of interest, OKT3D(IgG1) in its
      intact form, but not its F(ab')2, activated HuT-78 to secrete IL-2 in the absence
      of U937 suggesting therefore that OKT3D activates T cells in the absence of
      macrophages and provided its Fc domain is intact. All three anti-CD3 with IgG2b
      isotypes (but none with the IgG2a isotypes) activated HuT-78 to secrete IL-2 only
      when these antibodies were immobilized onto plastic (in the absence of U937). Of
      considerable importance, anti-CD3 activation of human T cells with the IgG2b
      isotype was efficient in the presence of murine macrophages. These observations
      would suggest that murine anti-CD3 with IgG2b and certain antibodies of IgG1
      isotypes, have inherent human T cell activating potential provided the Fc domain
      is in some manner activated, as for example, by binding to plastic or to Fc gamma
      R on murine macrophages. Macrophage cytokines are not essential. Therefore,
      ineffectual anti-CD3-mediated human T cell activation when using murine mAb with
      the IgG2b isotypes can best be explained on lack of Fc domain activation by human
      macrophages. This may indeed be the case as IgG2b and certain antibodies of IgG1
      isotype, failed to bind to Fc gamma R on macrophages at 37 degrees C. These
      studies would indicate that murine mAb with the IgG2b isotype may be potentially
      useful for human use, especially in situations where receptor blockade (without
      cell activation) is of prime importance.

PMID- 9243291
TI  - Hepatitis B virus binding to leucocyte plasma membranes utilizes a different
      region of the preS1 domain to the hepatocyte receptor binding site and does not
      require receptors for opsonins.
AB  - A quantitative assay of hepatitis B virus (HBV) binding to hepatocyte plasma
      membranes was adapted to show that leucocyte plasma membranes bind serum-derived
      HBV saturably, and that this binding is inhibited using synthetic peptides
      representative of the large envelope protein of HBV. Using a panel of ligand
      blocking monoclonal antibodies (mAb) to opsonin receptors, it was shown that the
      three classes of Fc gamma R and CR3 are not major receptors for HBV on leucocytes
      or hepatocytes. It was also shown that HBV does not utilize the receptor for IgA,
      Fc alpha R, for attachment to leucocytes, despite reported sequence homology
      between the large envelope protein of HBV and the Fc portion of human IgA.
      Evidence is presented that the receptor for HBV on leucocytes may differ from the
      hepatocyte receptor(s), based on synthetic peptide inhibition assays of HBV
      binding. Furthermore, it was observed that glycosaminoglycans influence the HBV
      liver and leucocyte interactions, providing evidence that HBV attachment may be a
      multi-stage process.

PMID- 9243293
TI  - Antarctic isolation: immune and viral studies.
AB  - Stressful environmental conditions are a major determinant of immune reactivity.
      This effect is pronounced in Australian National Antarctic Research Expedition
      populations exposed to prolonged periods of isolation in the Antarctic.
      Alterations of T cell function, including depression of cutaneous delayed-type
      hypersensitivity responses and a peak 48.9% reduction of T cell proliferation to
      the mitogen phytohaemagglutinin, were documented during a 9-month period of
      isolation. T cell dysfunction was mediated by changes within the peripheral blood
      mononuclear cell compartment, including a paradoxical atypical monocytosis
      associated with altered production of inflammatory cytokines. There was a
      striking reduction in the production by peripheral blood mononuclear cells of the
      predominant pro-inflammatory monokine TNF-alpha and changes were also detected in
      the production of IL-1, IL-2, IL-6, IL-1ra and IL-10. Prolonged Antarctic
      isolation is also associated with altered latent herpesvirus homeostasis,
      including increased herpesvirus shedding and expansion of the polyclonal latent
      Epstein-Barr virus-infected B cell population. These findings have important long
      term health implications.

PMID- 9243294
TI  - Interleukin-5 and eosinophils induce airway damage and bronchial hyperreactivity
      during allergic airway inflammation in BALB/c mice.
AB  - The cytokines IL-4 and IL-5 secreted from antigen-activated CD4+ T cells are
      thought to play central roles in the clinical expression and pathogenesis of
      asthma. However, there is conflicting evidence in animal models of allergic
      airway inflammation as to the relative importance of IL-5 and eosinophils to the
      mechanisms underlying the induction of bronchial hyperreactivity and
      morphological changes to the airways in response to aeroallergen. In a recent
      investigation, the development of aeroallergen-induced bronchial hyperreactivity
      in BALB/c mice was thought to be exclusively regulated by IL-4, with no role for
      IL-5 or eosinophils being demonstrated. In contrast, allergic airway disease
      could not be induced in IL-5-deficient mice of the C57BL/6 strain. A model of
      allergic airway inflammation, which displays certain phenotypic characteristics
      of late-phase asthmatic responses, was used in the present investigation to
      establish a role for IL-5 and eosinophils in the initiation of bronchial
      hyperreactivity and in the pathogenesis of allergic airway disease in BALB/c
      mice. Sensitization and repetitive aerosolization of mice with ovalbumin resulted
      in a severe airway inflammatory response which directly correlated with the
      induction of extensive airway damage and bronchial hyperreactivity to beta
      methacholine. Treatment of mice with anti-IL-5 mAb before aeroallergen challenge,
      abolished blood and airway eosinophilia, lung damage and significantly reduced
      bronchial hyperreactivity. These results show that IL-5 and eosinophilic
      inflammation play a substantial role in the pathophysiology of allergic airway
      disease and, moreover, that aeroallergen-induced bronchial hyperreactivity is not
      exclusively regulated by IL-4. These results also suggest that eosinophils are
      predominantly responsible for regulating aeroallergen-induced structural changes
      to the airways which contribute, in part, to the mechanism underlying the
      induction of bronchial hyperreactivity. Thus, there are at least two distinct
      pathophysiological mechanisms for the induction of aeroallergen-induced airway
      occlusion.

PMID- 9243295
TI  - A recombinant GM-CSF-PE40 ligand toxin is functionally active but not cytotoxic
      to cells.
AB  - A granulocyte/macrophage colony-stimulating factor (GM-CSF)-Pseudomonas exotoxin
      (PE) 40 fusion protein was constructed for potential use in the treatment of
      myeloid leukaemias, as a conditioning agent prior to allogeneic bone marrow
      transplantation or for ex vivo purging of malignant cells prior to autologous
      bone marrow transplantation. The GM-CSF-PE40 fusion protein successfully binds to
      the GM-CSF receptor and is capable of initiating a mitogenic signal similar to
      native GM-CSF in the GM-CSF-dependent TF1 cell line. The toxin component also
      appears to be fully functional as determined by an in vitro adenosine diphosphate
      ribosylation assay. The GM-CSF-PE40 fusion protein, however, was not cytotoxic to
      a number of myeloid leukaemia cell lines. It is suggested that the mechanism of
      internalization of the GM-CSF receptor is not appropriate for the translocation
      of PE to the cytosol where it can fulfil its cytotoxic potential.

PMID- 9243296
TI  - Differential expression of protein tyrosine kinases and their phosphorylation in
      murine Th1 cells anergized with class II MHC-peptide complexes.
AB  - In resting T cell clones, antigen presentation with immobilized anti-CD3 or anti
      T cell receptor (TCR) is known to result in a state of anergy as characterized by
      unresponsiveness to normal antigenic restimulation. Similarly, T cell
      unresponsiveness could be induced by immobilized (plate-coated) complexes of
      purified class II MHC and antigenic peptide. It is not clearly defined whether
      the engagement of TCR by immobilized anti-TCR or immobilized class II MHC-peptide
      complexes generates similar or differential signals during the induction of T
      cell unresponsiveness. In order to address the initial signalling events induced
      by TCR occupancy with anti-TCR and class II MHC-peptide molecules, the expression
      of three critical protein tyrosine kinases (PTK) and their phosphorylation were
      investigated in the present study using a murine T cell clone (HS17) restricted
      for IAS and myelin basic protein (MBP (91-103)) peptide. The anergic T cells
      induced by immobilized IAS-MBP (91-103) complex or anti-TCR (H57) showed
      differential expression of lck (56 kDa) and Zap-70 (70 kDa) proteins. In both
      systems, however, the induction of T cell unresponsiveness was accompanied by
      increased level of fyn (59 kDa) expression. When analysed for the total tyrosine
      phosphorylation of PTK, anergic HS17 T cells induced by both molecules showed
      increased phosphorylation associated with only the fyn protein. These results
      suggest that the signal transduction events induced by immobilized class II MHC
      peptide complexes and anti-TCR are distinct, although both can initiate signals
      that lead to increased fyn expression and phosphorylation. In addition, the
      present study supports the evidence for the important functional association of
      fyn protein with direct TCR engagement in T cell signalling.

PMID- 9243297
TI  - Expression of both Th1 and Th2 cytokines correlates with the histological
      rejection of MHC-matched and MHC-mismatched foetal pancreas allografts in mice.
AB  - Foetal mouse pancreatic islet grafts were used to investigate differences in the
      histological appearance and cytokine expression pattern during acute rejection of
      fully MHC-mismatched, and MHC-matched but minor histocompatibility-mismatched
      (mH) allografts. Grafts of foetal islet tissue from non-obese diabetic mice under
      the kidney capsule of non-immunosuppressed MHC and mH-disparate BALB/c mice were
      rejected by day 9, whereas the rejection of only mH-disparate C3H tissue into CBA
      mice occurred between 11 and 15 days. In both situations enhanced expression of
      transcripts for Th1 (IL-2, IFN-gamma, TNF-beta) and Th2 cytokines (IL-4, IL-6, IL
      10) was demonstrable at the peak of infiltration of immune cells into the graft
      site, indicating a close association of these cytokines with graft destruction.
      Besides these kinetic differences no variation in the expression pattern of the
      tested cytokines could be demonstrated, indicating that the allograft response in
      either combination leads to enhanced expression of pro-inflammatory cytokines
      which could contribute to graft destruction.

PMID- 9243298
TI  - Hypothesis: MHC class I, rather than just a flagpole for CD8+ T cells is also a
      protease in its own right.
AB  - Ever since the discovery of MHC class I restriction and the onslaught of the dual
      receptor hypothesis, MHC class I has been perceived as a passive entity in TCR
      recognition and the appropriate antigen processing and presentation pathways.
      However, numerous experimental observations and theoretical considerations are
      difficult or unable to be explained by the accepted mechanism of class I antigen
      presentation. Proteases within and outside the endoplasmic reticulum (ER) are
      evoked to be solely responsible for the generation of the appropriate 8-10 amino
      acid-long peptides associated with MHC class I. A MHC class I with site
      restricted ER protease activity would overcome most of the present difficulties
      in explaining MHC class I antigen presentation.

PMID- 9243299
TI  - The spleen, IgG antibody subsets and immunity to Plasmodium berghei in rats.
AB  - The development of IgG subclass-specific antibody responses to Plasmodium berghei
      in spleen-chimeric rats were monitored to determine if there was any relationship
      between IgG subset profiles and resistance. Strongly immune eusplenic rats
      respond to challenge with P. berghei by producing high levels of parasite
      specific IgG2a, IgG2b and IgG2c but only modest levels of IgG1. Splenectomy
      profoundly affects the antibody response to infection. Thus, in splenectomized
      immunized rats, which harbour a chronic parasitaemia of 1%, the IgG2a, IgG2b and
      IgG2c responses peak 1 week later than in eusplenic immunized rats although the
      size of the peak is similar. More marked effects are apparent in the IgG1
      response, the magnitude of which is far greater in splenectomized immunized rats
      than eusplenic immunized rats. Similar antibody profiles are seen in
      splenectomized immunized rats transplanted with a naive spleen. In contrast,
      splenectomized naive rats receiving either a transplant of a spleen from an
      immune rat or a transfer of immune spleen cells have high levels of IgG2a, IgG2b
      and IgG2c but modest levels of IgG1. However, only the former group of rats
      completely clears the parasite, the latter maintaining a chronic 1% parasitaemia.
      Thus, although complete resistance to P. berghei is always associated with high
      levels of parasite-specific IgG2a, IgG2b and IgG2c plus modest levels of IgG1,
      this is not a sufficient set of conditions to guarantee complete immunity. The
      IgG subset profile may be related to cytokine production; IFN-gamma was detected
      in the sera of rats receiving spleens from rats immune to P. berghei (modest IgG1
      responses) but not in rats receiving spleens from naive animals (pronounced IgG1
      responses).

PMID- 9243300
TI  - Topical drug vehicle effects on skin and inflammation.

PMID- 9243301
TI  - 16 beta-Methyl-17 alpha,21-diesterified glucocorticoids as partial agonists of
      glucocorticoid in rat endotoxin-induced inflammation.
AB  - OBJECTIVE AND DESIGN: We investigated the anti-inflammatory effects of 16 beta
      methyl-17 alpha,21-diesterified glucocorticoids which are well known as potent
      topical glucocorticoids in man on endotoxin-induced uveitis (EIU) in rats.
      MATERIAL: Female Lewis rats were used. TREATMENT: Glucocorticoids were instilled
      (0.01%-1.0%) or subcutaneously injected (0.1-10 mg/kg) to rats. METHODS: To
      elicit EIU, LPS (500 micrograms/kg) was injected into the footpad of rats. Twelve
      hours after LPS injection, cell number in aqueous humor was counted by flow
      cytometry. Endotoxin-induced in vivo tumor necrosis factor-alpha (TNF-alpha)
      production was also examined. RESULTS: 16 beta-methyl-17 alpha,21-diesterified
      glucocorticoids showed no effects or some enhancement of cell infiltration into
      the aqueous humor in EIU by topical instillation. Systemic injection of these
      glucocorticoids showed only weak inhibition of cell infiltration and TNF-alpha
      production. On the other hand, betamethasone phosphate strongly inhibited the
      cell infiltration and TNF-alpha production. Combined systemic injection of 16
      beta-methyl-17 alpha,21-diesterified glucocorticoids and betamethasone phosphate
      reduced the inhibitory effects of the latter. CONCLUSIONS: These results suggest
      that 16 beta-methyl-17 alpha,21-diesterified glucocorticoids might act as partial
      agonists of glucocorticoid in rats.

PMID- 9243302
TI  - Effects of environmental stress on tissue survival and neutrophil recruitment in
      surgical skin flaps in relation to plasma corticosterone levels in the rat.
AB  - OBJECTIVE: Because glucocorticoid treatment can improve the survival of surgical
      skin flaps, we examined the influence of environmental stress on skin flap
      survival in the rat. MATERIAL: Female Sprague-Dawley rats. TREATMENT:
      Dexamethasone (1 mg/kg i.p.). METHODS: A standardized dorsal skin flap was raised
      and sutured back into position, and six days latter the percentage of flap
      survival was assessed. Corticosterone in rat plasma was measured using
      radioimmuno assay, and skin flap myeloperoxidase accumulation (reflecting
      neutrophil recruitment) was determined spectrophotometrically. RESULTS: Skin flap
      survival decreased gradually during a 10 day acclimatization period after
      transportation of the animals from the supplier, and plasma corticosterone levels
      were increased during the first 5 days of acclimatization compared to day 7 and
      10. Dexamethasone treatment of rats accustomed to their new environment for 10
      days increased flap survival to a level close to that observed in animals
      operated at day 1 after arrival. Flap surgery induced pronounced neutrophil
      recruitment into flap tissue, and this cell accumulation was greatly reduced in
      both the dexamethasone treated rats and in rats with elevated corticosterone
      levels. CONCLUSIONS: Skin flap survival in rats exposed to environmental stress
      may be significantly increased as compared to animals accustomed to their new
      environment for one week, possibly as a consequence of anti-inflammatory actions
      exerted by stress-induced elevations in plasma corticosterone. These findings
      emphasize the importance of strictly controlling environmental stress factors in
      studies of inflammation and tissue damage after surgical skin trauma.

PMID- 9243303
TI  - Analgesic activity of the novel COX-2 preferring NSAID, meloxicam in mono
      arthritic rats: central and peripheral components.
AB  - OBJECTIVE AND DESIGN: To study the characteristics and site of the analgesic
      action of meloxicam. SUBJECTS: Adult female Wistar rats. TREATMENT: Monoarthritis
      was induced (for behavioural studies) by injection of complete Freund's adjuvant
      into the ankle. Meloxicam was given for 5 days (0.1-4 mg/kg/ day i.p.).
      Inflammation of the knee or paw (for electrophysiology) was induced with
      carrageenan. Meloxicam was given i.v. (4-64 mg/kg). METHODS: Rats were tested
      daily for joint hyperalgesia, and hindlimb posture (behaviour). At post-mortem,
      joint stiffness, oedema and gastric lesions were assessed. In anaesthetised rats,
      nociceptive reflex responses to stimulation of the paw were compared
      (electrophysiology). Statistics were performed using one-way analysis of
      variance. RESULTS: Meloxicam reduced swelling and stiffness of the inflamed
      joint, joint hyperalgesia (ID50 = 0.4 +/- 0.4 mg/kg/ day) and spontaneous pain
      related behaviour. It also inhibited peripherally mediated reflex responses to
      stimulation of inflamed tissue (ID50 = 7.6 +/- 0.8 mg/kg.i.v.) without affecting
      centrally mediated reflexes. CONCLUSIONS: Systemic meloxicam produces analgesia
      largely via peripheral mechanisms. The rapidity of its actions indicates a direct
      effect on sensitised nociceptors.

PMID- 9243304
TI  - Anti-arthritic activity of hydroxamic acid-based pseudopeptide inhibitors of
      matrix metalloproteinases and TNF alpha processing.
AB  - OBJECTIVE AND DESIGN: The effects of two hydroxamate inhibitors of
      metalloproteinase and tumor necrosis factor alpha (TNF alpha) processing on
      endotoxin-induced plasma TNF alpha and arthritic lesions in adjuvant-induced
      arthritic (AA) rats were determined. MATERIAL AND TREATMENT: BB-1101 and BB-1433
      were administered orally twice daily to AA Lewis rats with an established disease
      (days 13 to 22). AA rats (day 16) or normal rats were injected with bacterial
      endotoxin and plasma levels of TNF alpha were also determined. METHODS: Hindpaw
      swelling was measured plethysmographically. Bone degradation was determined by
      radiography and bone mineral densitometry. TNF alpha was quantified using a
      sandwich ELISA. RESULTS: The hydroxamic-acid pseudopeptides inhibited plasma. TNF
      alpha levels in vivo and significantly reduced swelling and bone degradation of
      the tibiotarsal joints of AA rats in the range of 10-50 mg/kg given orally (p <
      0.01 by Student's t-test). CONCLUSIONS: Thus, these novel compounds offer a new
      disease modifying therapy for arthritis and the results also suggest that
      inhibition of TNF alpha production may contribute, at least in part, to their
      anti-arthritic activity.

PMID- 9243305
TI  - A peptide derived from neutrophil inhibitory factor (NIF) blocks neutrophil
      adherence to endothelial cells.
AB  - OBJECTIVE AND DESIGN: Peptides derived from neutrophil inhibitory factor (NIF), a
      known antagonist of Mac-1, were evaluated as inhibitors of neutrophil adherence.
      MATERIAL: In vitro assays of adherence employed: 1) human polymorphonuclear cells
      (PMN), 2) human umbilical vein endothelial cells (HUVEC), and 3) CHO cells
      expressing ICAM-1 (CHO-ICAM cells). TREATMENT: Cells, pretreated with NIF-derived
      peptides (0.1-100 microM) for 10 minutes, were permitted to adhere for 20 min in
      the continued presence of peptide. METHODS: Cell-based assays: 1) PMN adherence
      to HUVEC, 2) PMN adhesion to immobilized human serum proteins, and 3) adherence
      of CHO-ICAM cells to immobilized Mac-1. RESULTS: A NIF-derived peptide of 29
      amino acids blocked PMN adherence to HUVEC, but behaved somewhat differently than
      the parent NIF protein. NIF specifically antagonized Mac-1 dependent adherence,
      but the peptide blocked neutrophil adherence that was dependent upon both Mac-1
      and LFA-1 integrins. CHO-ICAM adherence to Mac-1 was blocked by NIF, but not by
      the peptide. Binding studies with NIF and the peptide indicate that the molecules
      bind to different sites. CONCLUSIONS: A peptide derived from NIF blocks PMN
      adherence but, unlike NIF, the mechanism of action is not mediated by direct
      antagonism Mac-1.

PMID- 9243306
TI  - The efficacy of BAY y 1015 in dextran sulfate model of mouse colitis.
AB  - OBJECTIVE AND DESIGN: There is crucial evidence that leukotrienes are significant
      mediators of inflammation in inflammatory bowel diseases (IBD). Thus, selective
      inhibition of leukotriene synthesis is believed to provide a novel approach to
      therapy of IBD. The aim of the study is to study the efficacy of a potent 5
      lipoxygenase activating protein inhibitor (FLAP), BAY y 1015 in a dextran sulfate
      model of mouse colitis. MATERIAL: Outbred female mice weighing approximately 25
      grams were used to produce acute or chronic colitis by feeding 5% dextran sulfate
      in drinking water. TREATMENT: Colitic mice were treated with placebo (3% starch
      suspension, 0.1 ml. p.o., bid) or BAY y 1015 at 8 or 24 mg/kg, p.o., bid or
      olsalazine, 150 mg/kg/day, p.o. METHODS: Efficacy was determined by measuring
      daily disease activity index (DAI), quantitative histological scores, qualitative
      histology and measurement of tissue myeloperoxidase (MPO) and leukotriene B4
      (LTB4) levels. RESULTS: BAY y 1015 was significantly more effective in improving
      the qualitative histology, inhibiting the DAI, inflammation scores (37-79%),
      crypt scores (28-71%), MPO (49-57%) and LTB4 levels (56-63%) compared to placebo
      treatment at all levels of colitis. The two doses of BAY y 1015 were equipotent
      in decreasing TLB4 levels. BAY y 1015 was significantly better than olsalazine in
      two of the three protocols used in this study. In the advanced disease level both
      doses of BAY y 1015 were equipotent in inhibiting crypt and (28-32%) inflammation
      scores (34-36%), LTB4 (34-56%) and MPO 41-49%) compared to olsalazine.
      CONCLUSION: This study suggests the possibility of investigating the use of this
      compound for the treatment of human inflammatory bowel diseases.

PMID- 9243307
TI  - Immunohistochemical study of calpain-mediated alpha-crystallin proteolysis in the
      UPL rat hereditary cataract.
AB  - The UPL (Upjohn Pharmaceutical Limited) rat is a dominant hereditary cataract
      model that develops early-onset cataracts (E-type) in rats homozygous for the
      trait, and late-onset cataracts (L-type) in heterozygous rats. Using antibodies
      specific to the calpain-proteolyzed forms of alpha-crystallin, we determined
      their immunohistochemical localization of the L- and E-rat lenses.
      Immunoreactivity indicating the proteolyzed forms was detected and found
      restricted to degenerated lens fibers of the mature stage of the L-rat cataract.
      Lenses from E-rats, which have abnormally elongated lens fibers during the fetal
      period, had proteolyzed alpha-crystallin forms at 1 week of age. The results of
      this present study indicate that calpain-mediated proteolysis of alpha-crystallin
      occurred in the UPL rat lenses during cataract formation and that calpain may be
      an important factor in the development of complete lens opacification.

PMID- 9243308
TI  - Pathophysiology of cataracts: copper ion and peroxidation in diabetics.
AB  - The concentration of copper ion in cataractous lenses was higher than that in
      clear lenses. The concentration of copper ion was significantly higher in
      subjects with diabetes (DM group) than in subjects without diabetes (control
      group). The concentration of Cu2+ ion was significantly greater than that of Cu+
      ion in the DM group. Furthermore, the concentration of copper ion unconjugated to
      protein was higher than that of protein-conjugated copper ion. It is assumed that
      in the cataractous lenses of the DM group, a decrease in the reactivity of the
      copper-containing enzyme superoxide dismutase and an increase in hydrogen
      peroxide concentration leads to the generation of hydroxyl radicals from the
      Fenton's-type reaction. In diabetes, an increase in lenticular glucose induces
      glycation with the release of copper ion from copper-containing enzymes, thus
      increasing the concentration of lenticular copper ion. As a result, superoxide
      scavenging activity is reduced and peroxide lipid concentration is increased.
      This is assumed to result from the hyperactivity of the peroxidation cascade.

PMID- 9243309
TI  - Cytoskeleton and tissue origin in the anterior cynomolgus monkey eye.
AB  - We studied cytoskeletal proteins and other markers for embryologic origin in the
      outflow pathways of the aqueous humor, cornea, sclera, and ciliary muscle of the
      cynomolgus monkey. The corneal endothelium and trabecular cells stained with
      markers for vimentin, smooth muscle cell alpha-actin, F-actin, spectrin,
      vinculin, and talin. The endothelium of Schlemm's canal stained with markers for
      vimentin, spectrin, and F-actin. These results suggest that trabecular cells are
      a kind of myofibroblast and support the belief that the endothelial cells of
      Schlemm's canal are vascular in origin. Fibrillary staining with antibodies to
      vimentin, spectrin, neurofilament protein, and glial acid fibrillary protein was
      observed along and between the ciliary muscle cells. Cells in the deep sclera
      adjacent to the supraciliary space stained with antibodies to smooth muscle alpha
      actin, alpha-vinculin, talin, and desmin. These cells may anchor ciliary muscle
      cells into the sclera or may be developmental remnants of ciliary muscle cells.
      Leu 19 immunoreactivity was found in the corneal endothelium, in all trabecular
      cells, in ciliary muscle cells, and in keratocytes and fibroblasts in the
      superficial part of the cornea and sclera. All of these cells are therefore
      likely to express neural cell adhesion molecules indicating neuroectodermal
      origin.

PMID- 9243310
TI  - Endothelin-1 and intraocular inflammation in pigmented rabbit eyes.
AB  - We assessed the function of Endothelin-1 (ET-1) in the development of anterior
      chamber inflammation in pigmented rabbit eyes. After the injection of ET-1
      solution (10(-13), 10(-11), 10(-9), or 10(-7) M, diluted with 300 microL of
      artificial aqueous humor) into the anterior chamber, the aqueous protein
      concentration (APC) increased significantly in a dose-dependent fashion. Peak
      effects were observed 1-2 hours posttreatment. The APC returned to normal 12
      hours after the injection. Pretreatment with antiprostaglandin agents, topical
      indomethacin, or intravenous diclofenac sodium suppressed the increase in APC. In
      an endotoxin-induced experimental uveitis model, the ET-1 concentration in the
      aqueous humor was significantly higher than in normal controls, as was the plasma
      ET-1 level. These results suggest that ET-1 is an important mediator in ocular
      inflammatory reactions via arachidonic acid cascade.

PMID- 9243311
TI  - Cross-linking of vitreous collagen and degradation of hyaluronic acid induced by
      bilirubin-sensitized photochemical reaction.
AB  - To determine the mechanisms of vitreous liquefaction following vitreous
      hemorrhage, we investigated the effects of the free radicals produced by a
      bilirubin-sensitized photochemical reaction on collagen and hyaluronic acid (HA).
      Bovine vitreous collagen and HA were irradiated by visible light in the presence
      of bilirubin, which is produced from the degradation of hemoglobin, as a
      photosensitizer. Changes in molecular weight were monitored by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis for the collagen, and high-performance
      liquid chromatography for the HA. We found that free radicals caused an increase
      in high-molecular-weight components and insolubilization of the vitreous
      collagen, and a decrease in the molecular weight of HA. The changed molecular
      properties of the vitreous collagen could be attributed to the extensive cross
      linking of the molecules. This cross-linking and the degradation of HA, both
      induced by the bilirubin-sensitized photochemical reaction, may contribute to
      vitreous liquefaction following vitreous hemorrhage.

PMID- 9243312
TI  - Retinal light damage: protective effect of alpha-tocopherol.
AB  - We studied histologically the protective effect of alpha-tocopherol to retinal
      light damage. After 3-week-old albino rats were fed with an alpha-tocopherol
      deficient or supplemented diet and kept in a 12-hour dim light/12-hour dark
      environment for 8 weeks, each animal was exposed to intense light (2500 lux) for
      1, 3, 6, 12, 24, and 72 hours. The eyes were enucleated and prepared for
      transmission electron microscopy study and image analysis of phagosomes. Before
      light exposure, the alpha-tocopherol content of the neural retina of the
      deficient and supplemented groups was 0.3 microgram and 23.34 micrograms,
      respectively. After 1- and 3-hour exposures, morphological changes in the retinal
      pigment epithelium and photoreceptor membranes were more extensive in the
      deficient group than in the supplemented group. After a 24-hour exposure,
      pyknotic photoreceptor nuclei were more numerous in the deficient group than the
      supplemented group. After 3-, 6-, and 12-hour exposures, large phagosomes were
      more numerous in the deficient group than in the supplemented group. These
      findings suggest that alpha-tocopherol can protect the retina from light injury
      for up to 24 hours of exposure.

PMID- 9243313
TI  - Epiretinal membrane formation in Terson syndrome.
AB  - Clinical features of epiretinal membranes were examined in 22 eyes of 13 patients
      with Terson syndrome who were treated with pars plana vitrectomy. The shape and
      localization of the epiretinal membranes were intraoperatively evaluated and
      correlated with the presence or absence of posterior vitreous detachment (PVD).
      Patients with complete PVD, but with no membrane found during surgery, were
      followed postoperatively. Membrane formation ultimately developed in 13 of the 22
      eyes. In eight eyes, PVD was incomplete and the epiretinal membrane was found at
      the optic disc or along the temporal vascular arcades, displaying retinal folds
      and vascular tortuosity. Three eyes had massive tractional retinal detachment;
      five of those with complete PVD developed a thin epiretinal membrane around the
      posterior pole that became more apparent during long-term follow-up. From these
      observations, we can classify epiretinal membrane formation in Terson syndrome
      into two groups: with complete, or with incomplete, PVD. It also appears that
      multiple pathological processes involving the vitreoretinal interface were
      responsible for the formation of epiretinal membranes.

PMID- 9243314
TI  - Differentiation of neovascular maculopathies by nonphotic electrooculogram
      responses.
AB  - Four kinds of electrooculographic (EOG) responses for the retinal pigment
      epithelium (RPE) were studied to assess RPE integrity in neovascular macular
      diseases. In 20 eyes with age-related macular degeneration (ARMD), 13 fellow eyes
      of ARMD patients, eight eyes with central exudative chorioretinopathy (CECR), and
      seven unaffected eyes of CECR patients, we evaluated the light peak/dark trough
      ratio, and the hyperosmolarity, Diamox, and bicarbonate responses. We found no
      abnormalities in any ARMD eyes or fellow eyes of ARMD patients. In both the CECR
      eyes and unaffected eyes of CECR patients, however, the Diamox response was
      subnormal whereas the other three EOG responses remained normal. There was no
      significant difference in Diamox response between the CECR eyes and unaffected
      eyes of CECR patients. The selective deterioration of the Diamox response in
      CECR, but not in ARMD, can serve as a new index for differentiating between these
      similar conditions.

PMID- 9243315
TI  - Corticosteroid-induced central serous chorioretinopathy.
AB  - Five patients were identified by medical records and fluorescein angiography as
      having developed central serous chorioretinopathy (CSC) during corticosteroid
      treatment. These five and 28 previously reported corticosteroid-induced CSC
      occurrences were studied to clarify the differences between idiopathic CSC and
      corticosteroid-induced CSC. Nine previously reported occurrences of
      corticosteroid-induced multiple posterior pigment epitheliopathy (MPPE) were also
      reviewed. Corticosteroid-induced CSC patients were older and less male-dominant;
      in MPPE, female patients predominated and most had bilateral involvement. The
      onset of CSC was within 70 days of corticosteroid administration in the short
      latency group, and more than 6 months after administration in the prolonged
      latency group. Daily doses of prednisolone usually exceeded 20 mg in the short
      latency group and was less than 20 mg in the prolonged latency group.
      Immunosuppressive agents such as cyclophosphamide were related to a lower daily
      dose at onset.

PMID- 9243317
TI  - Anterior segment ischemia following pterygium surgery.
AB  - A 60-year-old woman developed anterior segment ischemia 1 week after an
      uneventful pterygium excision in the left eye. Corrected visual acuity fell from
      20/20 to 20/200. Ophthalmic examination found keratic precipitates on the corneal
      endothelium, ++ cells in the aqueous humor, and necrosis of the lower half of the
      iris with posterior synechiae resulting in a fixed and distorted pupil. On
      therapy of topical corticosteroid eyedrops hourly and atropine eyedrops three
      times a day, the iridocyclitis resolved in 2 weeks. At the final examination 3
      months after the surgery, the corrected visual acuity was 20/20. The atrophy of
      the lower half of the iris and posterior synechiae in the lower half of the
      pupil, giving the fixed and distorted pupil, were noted as sequelae. Iris
      fluorescein angiography revealed filling defects in the lower half of the iris
      but no leakage from iris vessels. Systemic evaluation was unremarkable except for
      mild hypertension. Doppler studies of carotid, ophthalmic, and central retinal
      arteries were normal. Mitomycin C, beta-irradiation and rectus muscle fixation
      sutures were not used. Only conjunctival dissection or episcleral cauterization
      were seen as possible causes of interference with the anterior segment blood
      supply. We believe this is the first report of anterior segment ischemia
      following pterygium surgery.

PMID- 9243316
TI  - Two cases of malignant lymphoma complicated by hemophagocytosis resembling
      orbital cellulitis.
AB  - Two patients with malignant lymphoma complicated by hemophagocytic syndrome (HPS)
      are reported. Their clinical signs at onset were similar to those of orbital
      cellulitis. Lymphoma complicated by hemophagocytosis is called lymphoma
      associated hemophagocytic syndrome (LAHS) and its prognosis is reported to be
      very poor. As far as we know, this is the first report in the ophthalmological
      field. In our patients, we suspected that the lesions occurred from the orbit or
      skin of this area. The first patient was a 22-year-old man and the second patient
      a 16-year-old girl. The diagnosis was very difficult at the onset of disease.
      They died within 6 months after the first ophthalmological examination. When
      orbital cellulitis is suspected and antibiotic therapy is ineffective, we should
      suspect HPS and should examine serum ferritin, which is a good marker of HPS.
      Early biopsy and consultation with a hematologist are very important.

PMID- 9243319
TI  - Immunohistochemical localization of MUC1 glycoprotein in the retina.

PMID- 9243318
TI  - Conjunctival injection, episcleral vessel dilation, and subconjunctival
      hemorrhage in patients with new tsutsugamushi disease.
AB  - Tsutsugamushi disease is found in two types: classical and new. There have been
      very few reports describing the ocular findings in patients with the new form. We
      have described four patients with this type, selected according to their clinical
      and laboratory findings, including immunofluorescent titers and polymerase chain
      reaction results. Eyes were examined by standard ophthalmic procedures. Patient 1
      had bilateral conjunctival injection and subconjunctival hemorrhage; patients 2-4
      had conjunctival injection and episcleral vessel dilation bilaterally. We believe
      that conjunctival injection is found in most eyes of patients with new
      tsutsugamushi disease.

PMID- 9243320
TI  - Structure and function of inositol 1,4,5-trisphosphate receptor.
AB  - Generation of intracellular Ca2+ signals in response to Ca(2+)-mobilizing stimuli
      is a critical event in the control of many cellular processes. Inositol 1,4,5
      trisphosphate (IP3) represents a dominant second messenger subserving the release
      of Ca2+ from intracellular store sites. The protein on the surface of which the
      IP3 receptor is located comprises an IP3-gated Ca2+ channel, and binding of IP3
      to this receptor triggers the release of Ca2+ through this channel. The receptor
      for IP3 displays a close resemblance to the ryanodine receptor, another
      intracellular Ca2+ channel, in many molecular and physiological properties. Many
      lines of evidence strongly suggest the central role that the IP3 receptor plays
      in the conversion of numerous external stimuli to intracellular Ca2+ signals
      characterized by complex spatiotemporal patterns such as Ca2+ waves and
      oscillations. In this review, we shall summarize our current knowledge of the
      structure and function of the IP3 receptor in order to understand the way how the
      activity of this important receptor is regulated to accomodate itself to the
      generation of diverse intracellular Ca2+ signals.

PMID- 9243321
TI  - Nicotinic agonist modulation of neurotransmitter levels in the rat frontoparietal
      cortex.
AB  - Anabaseine is a naturally occurring toxin that stimulates a variety of neuronal
      and muscle nicotinic receptors. GTS-21 [3-(2,4-dimethoxybenzylidene)anabaseine],
      an anabaseine derivative, selectively stimulates alpha 7-containing nicotinic
      receptors. Here we report the first in vivo study of the effects of these two
      nicotinic agonists on cortical extracellular acetylcholine (ACh), dopamine (DA),
      norepinephrine (NE) and serotonin (5-HT) levels, measured with a microdialysis
      probe placed within the frontoparietal cortex in the absence of a cholinesterase
      inhibitor. At 3.6 mumol/kg, s.c., anabaseine increased cortical ACh and NE above
      baseline values without significantly affecting DA and 5-HT. The ACh and NE
      elevations were inhibited by i.p. pre-administration (4.9 mumol/kg) of the
      nicotinic antagonist mecamylamine (Mec). In contrast, GTS-21 (3.6 mumol/kg, s.c.)
      significantly increased NE and DA without affecting ACh and 5-HT levels.
      Following Mec injection, GTS-21 increased ACh 25-fold and 5-HT 13-fold, while NE
      and DA levels were slightly decreased in comparison with GTS-21 alone. We suggest
      that at the dose used, Mec may preferentially block high affinity nicotinic
      receptors which normally provide an inhibitory influence upon ACh release,
      thereby permitting expression of the complete stimulatory effect of GTS-21 on
      neuronal alpha 7-receptors. GTS-21 and other receptor subtype-selective nicotinic
      agonists should be helpful in clarifying the roles of particular nicotinic
      receptors in modulating cortical neurotransmitter levels.

PMID- 9243322
TI  - Beneficial effects of dilazep on the palmitoyl-L-carnitine-induced derangements
      in isolated, perfused rat heart: comparison with tetrodotoxin.
AB  - The present study was carried out to determine the effect of dilazep, having an
      inhibitory effect on the Na+ channel, on the mechanical dysfunction and metabolic
      derangements induced by palmitoyl-L-carnitine in isolated rat heart and to
      compare the effect of dilazep with that of tetrodotoxin, a specific inhibitor of
      the Na+ channel. Rat hearts were perfused aerobically at a constant flow
      according to Langendorff's technique and paced electrically. Palmitoyl-L
      carnitine (5 microM) decreased the left ventricular developed pressure and
      increased the left ventricular end diastolic pressure (i.e., it produced
      mechanical dysfunction), decreased the tissue level of adenosine triphosphate and
      increased the tissue level of adenosine monophosphate (i.e., it produced
      metabolic derangements). These mechanical and metabolic alterations induced by
      palmitoyl-L-carnitine were attenuated by either dilazep (1 microM) or
      tetrodotoxin (3 microM). On the other hand, neither dilazep nor tetrodotoxin
      modified the mechanical function and energy metabolism of the normal (palmitoyl-L
      carnitine-untreated) heart. These results suggest that inhibition of the Na+
      channel with dilazep or tetrodotoxin is responsible, at least in part, for
      attenuating the palmitoyl-L-carnitine-induced mechanical dysfunction and
      metabolic derangements in the heart.

PMID- 9243323
TI  - Muscarinic autoinhibition and modulatory role of protein kinase C in
      acetylcholine release from the myenteric plexus of guinea pig ileum.
AB  - The modulatory role of protein kinase C on phospholipase A2, activation of which
      had been suggested to result in acetylcholine release from cholinergic neurons,
      was studied in longitudinal muscle preparations with the myenteric plexus of
      guinea pig ileum. The relationship of muscarinic autoinhibition to the modulation
      was also examined. Phorbol-12,13-dibutyrate (PDBu), an activator of protein
      kinase C, dose-dependently increased spontaneous and electrical field stimulation
      induced acetylcholine releases from the preparation. The inhibitors of protein
      kinase C, staurosporine and calphostin C, inhibited the stimulatory effects of
      PDBu, but neither inhibitor affected spontaneous or electrical field stimulation
      induced acetylcholine release in the absence of PDBu. On the other hand, atropine
      significantly increased electrical field stimulation-induced release by blocking
      a muscarinic autoinhibitory mechanism. Under the auto-inhibition blocked
      condition, U73122, an inhibitor of phospholipase C, and staurosporine
      significantly inhibited the effect of atropine on electrical field stimulation
      induced release. An inhibitor of phospholipase A2, mepacrine, inhibited PDBu
      induced acetylcholine release and also inhibited the effect of atropine on
      electrical field stimulation-induced release. An activator of phospholipase A2,
      melittin, and a product of the phospholipase, arachidonic acid, increased the
      spontaneous and electrical field stimulation-induced releases. These results
      suggest that the phospholipase C-protein kinase C system modulates acetylcholine
      release from cholinergic neurons by activating phospholipase A2 in the myenteric
      plexus of guinea pig ileum, and the activation of muscarinic autoreceptor may
      negatively modulate acetylcholine release at a point upstream of the system.

PMID- 9243324
TI  - Furosemide-sensitive calcium rise induced by GABAA-receptor stimulation in
      cultures of embryonic rat striatal neurons.
AB  - Changes in [Ca2+]i induced by gamma-aminobutyric acid (GABA) were investigated in
      primary cultured neurons obtained from fetal rat striatum. GABA and muscimol
      induced [Ca2+]i rise, and bicuculline blocked the effect of GABA. The [Ca2+]i
      elevating effect of GABA was also abolished by removal of extracellular Ca2+ or
      by application of nicardipine. Furthermore, furosemide, an inhibitor of Na+/K+/
      2Cl- co-transport, reversibly inhibited the GABA-induced [Ca2+]i rise. These
      results suggest that due to the elevated level of intracellular Cl- maintained by
      Na+/K+/2Cl- transport activity in these neurons, opening of GABAA-receptor
      associated Cl- channels results in Cl- efflux, leading to membrane depolarization
      and activation of L-type voltage-dependent Ca2+ channels.

PMID- 9243325
TI  - Chronic therapy with nipradilol, a beta-adrenergic blocker, attenuated left
      ventricular remodeling following myocardial infarction in rats.
AB  - We determined whether chronic treatment with nipradilol, a beta-blocker with
      vasodilating action, reduces left ventricular cavity dilation (LV remodeling)
      following myocardial infarction and improves cardiac performance. Myocardial
      infarction was produced by coronary artery ligation in 16-week-old female rats
      and then the rats were treated for 3-4 months with nipradilol (10 mg/kg/day) or
      vehicle (0.5% carboxymethylcellulose). The effect of nipradilol on LV remodeling
      was evaluated by assessing the left ventricular end-diastolic volume index
      (LVEDVI) and passive pressure-volume relation curve. Since LVEDVI depends on the
      infarct size, LVEDVI was compared between the vehicle- and nipradilol-treated
      rats with similar infarct size (10-40%). At 3-4 months after myocardial infarct
      production, the left ventricular end-diastolic volume index in the vehicle
      treated rats with myocardial infarction was significantly increased, compared
      with that in the sham-operated rats without infarction. The nipradilol-treated
      rats had a significantly smaller left ventricular volume index than the vehicle
      treated rats (2.04 +/- 0.16 ml/kg in the vehicle-treated group vs 1.36 +/- 0.10
      ml/kg in the nipradilol-treated group, P < 0.01). The maximum cardiac index
      achieved by volume loading as an index of cardiac performance was significantly
      greater in the nipradilol group than the vehicle group (254.5 +/- 12.6 ml/min kg
      in the vehicle group vs 347.9 +/- 20.2 ml/min kg in the nipradilol group, P <
      0.01). These results suggest that chronic treatment of nipradilol attenuated left
      ventricular cavity dilation after myocardial infarction and improved cardiac
      performance.

PMID- 9243326
TI  - Effects of cAMP and cGMP on L-type calcium channel currents in rat mesenteric
      artery cells.
AB  - L-type Ca2+ channel currents in cultured rat mesenteric artery smooth muscle
      cells were recorded by the cell-attached patch-clamp technique. Depolarizing
      voltage steps from a holding potential of -40 mV elicited voltage-dependent
      inward Ba2+ currents. The inward currents were inhibited by nifedipine (10
      microM) but enhanced by Bay K 8644 (5 microM), which suggests that the inward
      currents are carried almost exclusively by L-type Ca2+ channels. Application of
      dibutyryl cAMP (0.1-1 microM) and forskolin (0.01-1 microM) enhanced the activity
      of these Ca2+ channels. The dibutyryl cAMP induced enhancement of Ca2+ channels
      was antagonized by the serine/threonine kinase inhibitor H-8 (1 microM).
      Application of 8-bromo-cGMP (0.01-1 microM) and the cGMP inducer nitroglycerin
      (0.01-1 microM) inhibited the activity of these Ca2+ channels, and the inhibition
      of channel activity induced by 8-bromo-cGMP was antagonized by the
      serine/threonine kinase inhibitor H-8 (1 microM). These results suggest that in
      rat mesenteric artery cells, the L-type Ca2+ channel current is enhanced by a
      rise in intracellular cAMP levels and suppressed by a rise in intracellular cGMP
      levels. Furthermore, cGMP-induced Ca2+ channel inhibition may play a role in the
      expression of the nitric oxide-mediated vasodilating action of drugs such as
      nitroglycerin and atrial natriuretic peptide.

PMID- 9243327
TI  - Effects of a new non-steroidal 5 alpha-reductase inhibitor, FK143, on the
      prostate gland in beagle dogs.
AB  - FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl] -
      butyric acid) is a new non-steroidal inhibitor of steroid 5 alpha-reductase (5
      alpha-reductase). The effects of FK143 on prostate size and histopathology of
      mature male beagle dogs were investigated and compared with those of finasteride
      (a steroidal 5 alpha-reductase inhibitor), and allylestrenol and chlormadinone
      acetate (CMA) (androgen receptor antagonists). FK143 was orally administered to
      the dogs daily for 12 weeks. At doses of 10 and 32 mg/kg, FK143 significantly
      reduced prostate volume to about 60% of the initial value, and dogs treated with
      FK143 showed a dose-dependent glandular epithelial atrophy in the prostate. FK143
      showed no abnormal changes in organ weights and histopathology of the adrenal,
      testis, pituitary and liver. The degree of prostate reduction in the dogs treated
      with FK143 (10 and 32 mg/kg) was almost the same as that by finasteride (1.0
      mg/kg) and smaller than that by allylestrenol (10 mg/kg) or CMA (10 mg/kg).
      However, allylestrenol increased liver weights, and CMA increased liver and
      reduced adrenal weights. These results demonstrate that FK143 can decrease the
      volume of the dog prostate without any influence on other organs, and they
      suggest that FK143 is a good candidate for the treatment for benign prostatic
      hyperplasia.

PMID- 9243328
TI  - Effect of phorbol esters on cytosolic Ca2+ level, myosin phosphorylation and
      muscle tension in high K(+)-stimulated bovine tracheal smooth muscle.
AB  - To determine the role of protein kinase C (PKC) in bovine tracheal smooth muscle
      contractility, we examined the effects of phorbol esters on cytosolic Ca2+ level
      ([Ca2+]i), myosin light chain (MLC) phosphorylation and contractile force in
      intact muscle and contraction in a permeabilized preparation. In intact muscle,
      12-deoxyphorbol 13-isobutyrate (DPB, 1 microM) increased the force without
      changing [Ca2+]i. High K+ (72.7 mM) induced sustained contraction with sustained
      increase in [Ca2+]i. In the muscle stimulated by high K+, 50 nM DPB increased the
      contractile force without changing [Ca2+]i, and 1 microM DPB increased the
      contractile force with decreasing [Ca2+]i. Thus DPB shifted the [Ca2+]i/force
      relationship for high K+ to the lower [Ca2+]i in a concentration-dependent
      manner. In permeabilized muscle, DPB did not induce contraction in the absence of
      Ca2+ (< < 0 nM), but shifted the Ca2+/force relationship to the lower Ca2+
      levels. In the muscle stimulated with high K+, DPB (50 nM and 1 microM) increased
      MLC phosphorylation and force without changing the MLC phosphorylation/force
      relationship. DPB (1 microM) increased PKC activity estimated by the
      translocation from the cytoplasm to the membrane. These results suggest that DPB
      increases the Ca2+ sensitivity of MLC phosphorylation via the activation of PKC.
      Furthermore, DPB at higher concentration has an inhibitory effect on stimulated
      [Ca2+]i.

PMID- 9243329
TI  - Modulation of tyrosine kinase activity has multiple actions on insulin release
      from the pancreatic beta-cell: studies with lavendustin A.
AB  - We investigated the role of tyrosine kinases in the regulation of insulin release
      from a hamster beta-cell line, HIT T15, using selective tyrosine kinase
      inhibitors. Genistein increased the insulin release induced by glucose, but
      herbimycin A, tyrphostins and the erbstatin analogue failed to change the
      release. Lavendustin A at 0.1 nM-1 microM caused a concave-shaped inhibition of
      the insulin release stimulated by 7 mM glucose. The inhibitory effect of
      lavendustin A was overcome by higher concentrations of glucose. Lavendustin B,
      the negative control analogue, had no effect on the release. Lavendustin A at a
      nanomolar range progressively inhibited insulin release by high K+ (50 mM)
      depolarization, whereas the inhibitor did not change the insulin release by Ca2+
      ionophore (A23187). On the contrary, lavendustin A at 10 nM significantly
      increased insulin release when glucose-induced insulin release was enhanced by
      either 5 microM forskolin or 162 nM 12-O-tetradecanoylphorbol 13-acetate.
      Lavendustin A failed to influence the Ca(2+)-induced insulin release from HIT
      cells permeabilized with streptolysin-O. These findings suggest that tyrosine
      kinases may play versatile roles in the control of insulin release from the
      pancreatic beta-cell.

PMID- 9243330
TI  - The selective 5-hydroxytryptamine (5-HT)4-receptor agonist RS67506 enhances lower
      intestinal propulsion in mice.
AB  - Interactions of gastrointestinal prokinetic benzamides with 5-hydroxytryptamine
      (5-HT)3 and 5-HT4 receptors and the relation to their effects on gastrointestinal
      propulsion were investigated. Renzapride and zacopride potently inhibited 5-HT3
      receptor-mediated contractions in the guinea pig colon, whereas RS67506 (1-(4
      amino-5-chloro-2-methoxyphenyl)-3-[1-(2-methyl sulphonylamino)ethyl-4
      piperidinyl]-1-propanone hydrochloride), a selective 5-HT4-receptor agonist,
      showed no inhibition. RS67506, renzapride and zacopride all exerted 5-HT4
      receptor-mediated relaxation in the carbachol-precontracted rat oesophagus. In
      mice, RS67506 shortened the whole gut transit time, whereas renzapride and
      zacopride were reported to prolong it. Gastrointestinal prokinetic benzamides,
      which are selective for 5-HT4-receptor agonistic over 5-HT3-receptor antagonistic
      action, may be useful in treating gastrointestinal disorders associated with
      impaired lower intestinal propulsion such as constipation.

PMID- 9243331
TI  - Quenching of nitric oxide by an oral carbonaceous adsorbent.
AB  - The ability of carbonaceous particles (AST-120), originally developed as an
      enteral adsorbent of uremic toxins, to quench nitric oxide (NO) was tested. NO in
      solutions prepared by two methods [NO gas bubbling and NO generating system,
      i.e., decomposition of 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene]
      were determined by a NO-specific reduction of carboxy-2-phenyl-4,4,5,5
      tetramethyl-imidazoline-1-oxyl-3-oxide using an electron paramagnetic resonance
      spectrometry. NO concentrations were less in samples containing increasing
      concentrations of AST-120. In a separate study, nitrite concentrations in
      lipopolysaccharide-treated RAW264 cells were significantly less in incubation
      medium containing AST-120. Thus, AST-120 may be applicable as an enteral anti-NO
      agent.

PMID- 9243332
TI  - Enhancement by morphine of radiographic contrast media-induced histamine release
      in rat peritoneal mast cells.
AB  - In intravascular application of radiographic contrast media causes
      hypersensitivity reactions, in which histamine release may play a major role. We
      examined the interaction between contrast medium and morphine. Among the four
      nonionic contrast media examined, iopamidol showed the most marked histamine
      release from rat peritoneal mast cells in vitro. Although iopamidol and morphine
      themselves did not induce histamine release at concentrations up to 65 mgI/ml and
      3 mM, respectively, their combination resulted in a significant histamine
      release. These findings suggest that patients with exposure to medicines that
      induce histamine release may have a higher incidence and severity of
      hypersensitivity reactions to radiographic contrast media.

PMID- 9243333
TI  - The novel anti-rheumatic drug TA-383 has a macrophage migration enhancing
      activity.
AB  - We have investigated the effect of a novel anti-rheumatic drug, cis-2-(4
      chlorophenyl)-4,5-diphenyl-2-imidazoline hydrochloride (TA-383), on macrophages.
      TA-383 (> or = 10(-9) M) significantly stimulated rabbit alveolar macrophage (AM)
      migration, and its migration-stimulatory activity was more potent than those of L
      fucose (5 x 10(-3) M), lobenzarit disodium, bucillamine (SA-96) and
      salazosulfapyridine. In addition, TA-383 enhanced the production and/or release
      of macrophage migration enhancement factor by rabbit spleen cells. In vivo, TA
      383 (0.4 mg/kg, p.o.) has suppressive effects on picryl chloride-induced delayed
      type hypersensitivity and type II collagen-induced arthritis in mice. These
      results suggest that the anti-rheumatic activity of TA-383 may be exerted through
      the dispersion of macrophages from inflammatory sites.

PMID- 9243334
TI  - Reparative surgery of valves in the treatment of superficial venous
      insufficiency. External banding valvuloplasty versus high ligation or
      disconnection. A prospective multicentric trial.
AB  - OBJECTIVE: A prospective study was performed in order to compare results obtained
      in the treatment of early and/or limited primary varicose veins of the lower
      limbs using two different procedures: external valvuloplasty and high ligation or
      disconnection of the sapheno-femoral junction. MATERIALS AND METHODS: 116 limbs
      (113 patients) were selected. 57 with normal cusps in dilated valves were
      subjected to external valvuloplasty with Silicone prosthesis under Doppler
      control (intraoperative angioscopy in 16 cases); 59 limbs were subjected to high
      ligation or disconnection of the junction; 57 limbs out of 116 were subjected to
      complementary procedures. Duplex and photoplethysmographic examinations were
      performed before and after the surgical procedures in all patients. Doppler
      venous pressures were measured in 36 limbs and invasive pressures in 40 limbs.
      Patients were postoperatively followed up every 4 months until the 12th month.
      RESULTS: Indications for valvuloplasty were found in 8.2% of cases and in 66.3%
      of the early varices. Clinical results were slightly superior in the reparative
      surgery group. Thrombotic occlusion of the proximal long saphenous vein was
      significantly higher in the ligation-disconnection group. Results from
      photoplethysmography and venous pressure measurements indicated that both
      operations are equally effective in the elimination of reflux in the junction.

PMID- 9243335
TI  - Anti-cocaine catalytic antibodies--a novel approach to the problem of addiction.
AB  - Cocaine reinforces its self-administration in relation to the magnitude of and
      rate of rise to the peak serum concentration of the drug. Catalytic antibodies
      are artificial enzymes which could reduce serum cocaine concentrations, deprive
      the abuser of cocaine's reinforcing effect and thus favor extinction of the
      addiction. Catalytic antibodies are elicited by immunization with a stable analog
      of a transition-state for a chemical reaction. Through our new method for
      synthesizing phosphonate monoesters, we constructed several phosphonate-based
      transition-state analogs of cocaine hydrolysis. Using these analogs, monoclonal
      antibodies were elicited and, thus far, nine anti-analog antibodies with
      hydrolytic activity against cocaine have been identified, cloned and studied. The
      activity of one of these antibodies, 15A10, is sufficient to commence preclinical
      studies.

PMID- 9243336
TI  - Self-reported alcohol use patterns in a sample of male and female heavy smokers.
AB  - In an attempt to characterize differences among male and female smokers based on
      past and current alcohol use, we studied patterns of drinking, smoking, caffeine
      intake, and depression as a function of lifetime history of alcohol dependence
      and current drinking status in a community sample of current smokers. Subjects
      were 65 male and 152 female moderate-to-heavy smokers. The CAGE was used to
      screen for lifetime history of alcohol dependence; current drinking status was
      classified using self-reported number of alcoholic drinks/week. No significant
      differences were detected for smoking rate, scores on the Fagerstrom Test for
      Nicotine Dependence, or either coffee or total caffeine intake. Drinkers with a
      history of alcohol dependence drank significantly more per week than drinkers
      with no history, with significant gender differences and interaction effects
      emerging as well; the phenomenon was particularly pronounced in men. Drinkers of
      both genders with a history of alcohol dependence scored significantly higher on
      the Center for Epidemiological Studies-Depression scale, with means exceeding the
      cutoff of 16 associated with clinical depression. Since comorbidity of depression
      and alcohol dependence is known to exert a detrimental effect on ability to stop
      smoking, the number of individuals at risk for smoking cessation treatment
      failure may be much larger than might be inferred from data based on psychiatric
      assessments or collected in inpatient settings. Routine screening for depressive
      symptomatology combined with heavy alcohol use in primary care settings may
      therefore be helpful in identifying smokers in need of more intensive stop
      smoking interventions.

PMID- 9243337
TI  - Medical use of recreational drugs by AIDS patients.
AB  - A survey of 72 patients at an AIDS clinic regarding self-medication with
      recreational drugs for medical or psychological conditions related to their
      illness disclosed that marijuana was the primary drug used. The perceived benefit
      was for gastrointestinal conditions such as nausea, vomiting, indigestion and
      appetite improvement. Use of other "recreational" drugs as self-medication was
      reported to usually be ineffective or to worsen the condition they sought to
      help. Fifty-eight percent of patients reported some attempt to self-medicate.
      Thirty-two percent were currently using marijuana, and most admitted to pre-AIDS
      marijuana use. Fifty-seven percent of the sample reported some pre-AIDS drug use,
      primarily alcohol and marijuana. Results are discussed in terms of potential
      clinical problems arising from continued recreational drug use among AIDS
      patients.

PMID- 9243338
TI  - Dual diagnosis patients in the modified therapeutic community: does a criminal
      history hinder adjustment to treatment?
AB  - The efficacy of the drug-free therapeutic community (TC) in treating patients
      with chemical dependence and in rehabilitating persons with criminal histories
      has been extensively studied and is well established since the late 1960's. More
      recently, this format has been modified in order to treat individuals suffering
      from both addictive disorders and chronic, severe mental illness. In an indigent
      inner-city population, this latter group includes many patients who also have
      significant histories of criminal behavior. To date, there have been no
      systematic attempts to assess the impact of a history of criminality on the
      course of treatment of these patients, as they might be thought less adaptable to
      the milieu of a TC. In the current study, data from a sample of homeless male
      MICA patients were analyzed to determine if those patients with a history of
      criminal convictions were as likely as non-criminal patients to adjust
      effectively to the social milieu of a modified drug-free therapeutic community.
      Of 183 sequential admissions studied, 76 had never been convicted of a crime, 46
      had 1 conviction, and 61 had 2 or more. No differences were observed between the
      groups with respect to length of stay, social adjustment on admission, and change
      in social adjustment during the first two months of treatment. These findings
      suggest that a history of criminal conduct does not compromise a dually diagnosed
      patient's likelihood of engaging in the social contract necessary for successful
      treatment in a TC.

PMID- 9243339
TI  - The role of node-link maps in enhancing counseling efficiency.
AB  - Node-link mapping is a counseling tool that helps clients and counselors
      visualize relationships between ideas, actions, and feelings. Previous research
      has shown that methadone-maintained clients receiving mapping-enhanced counseling
      have more positive during-treatment outcomes (e.g., better session attendance and
      higher probability of clean urines) than those receiving standard counseling.
      Findings also suggest that mapping enhances the efficiency of counseling sessions
      by increasing "on task" attention and by reducing communication problems. In this
      study, mapping counseling was associated with greater coverage of collateral
      issues (i.e., issues indirectly related to drug use) than standard counseling and
      lower during-treatment use as indicated by urinalysis results.

PMID- 9243340
TI  - Treatment structure, client coping methods, and response to brief individual
      counseling: preliminary findings in a substance dependent sample.
AB  - In this paper we report preliminary treatment outcome findings for the first 16
      substance abuse patients who volunteered and qualified for a 12-week research
      treatment program. Eight patients were exposed to a high-structure, behaviorally
      oriented (HSB) individual counseling style, while the remaining eight were
      exposed to a low-structure, facilitative (LSF) style. 'Counselor effects' were
      controlled by having each of four counselors conduct both styles (two patients
      each) in serial but counterbalanced order; under these conditions treatment
      outcomes did not differ for patients randomly assigned to the different
      counselors. Outcomes also did not differ for the HSB and LSF clients with regard
      to retention, drug and alcohol use during treatment or for reported symptom
      reduction during the program as measured by the Addiction Severity Index. Though
      the LSF clients reported receiving more treatment benefits than did the HSB
      patients in their post-session ratings, this was not confirmed in the counselors'
      post-treatment ratings or in the other treatment response measures. Finally, with
      a few exceptions, patients scoring higher versus lower on four measures of
      coping, including conceptual and developmental levels of functioning, field
      independence and social independence, did not differ in their treatment outcomes.

PMID- 9243341
TI  - Treating the chemically dependent health professional.
AB  - Chemical dependence among health professionals is a significant problem, with a
      lifetime prevalence of approximately 10-15%. A physician who undertakes the
      challenge of treating other physicians for chemical dependence must have firm
      boundaries, and must be willing to provide extra time and patience. Denial of
      symptoms, countertransference and other pitfalls have been cited as prominent
      potential problems. Although there is evidence that physicians in general have
      excellent outcomes following chemical dependence treatment, mismanagement can be
      disastrous. Standards are suggested for centers that wish to treat this
      population.

PMID- 9243342
TI  - Cocaethylene toxicity.
AB  - Concurrent use of cocaine and alcohol produces another psychoactive substance
      known as cocaethylene which has pharmacological properties similar to that of
      cocaine but which has a plasma half-life three to five times that of cocaine.
      This slow removal from the body makes it an attractive drug for abuse. However,
      cocaethylene has been associated with seizures, liver damage, and compromised
      functioning of the immune system. It also carries an 18- to 25-fold increase over
      cocaine alone in risk for immediate death.

PMID- 9243343
TI  - Further studies on the anatomical distribution of CART by in situ hybridization.
AB  - CART (cocaine and amphetamine regulated transcript) is a novel, brain-enriched
      mRNA which predicts a novel protein without homology to any known protein or
      peptide. In situ hybridization studies have identified many expression sites in
      the brain and periphery as well as clarify its expression in three known areas.
      CART mRNA has been localized to ganglion cells of the retina, lamina X of the
      spinal cord, mitral and tufted cells of the olfactory bulb, barrel field neurons
      of the somatosensory cortex, the anterior pituitary, and the medulla of the
      adrenal cortex. The two alternatively spliced CART variants present in the rat
      brain were found to have identical and overlapping distributions in the rat
      forebrain. This central nervous system expression pattern suggests a role for
      CART in processing of peripheral sensory information. Its localization within the
      pituitary completes its identification within the three levels of the
      hypothalamic-pituitary-adrenal axis and perhaps suggests a role in mediating
      stress responses. CART's distribution and predicted protein sequence is
      reminiscent of characteristics shared by many brain neuropeptides such as
      proopiomelanocortin; CART may encode a new peptide transmitter or signaling
      molecule.

PMID- 9243344
TI  - Identification and localization of dopamine receptor subtypes in rat olfactory
      mucosa and bulb: a combined in situ hybridization and ligand binding
      radioautographic approach.
AB  - Olfactory bulb (OB) of mammals contains a large population of dopaminergic
      interneurons within the glomerular layer. Dopamine has been shown in vivo to
      modulate several aspects of olfactory information processing. The dopamine
      receptors of olfactory bulb and mucosa are assessed here at the levels of mRNAs
      and radioligand binding sites with presently available tools. D1A mRNA was found
      in OB glomerular-, plexiform-, mitral-cell and granular layers, but not in
      olfactory mucosa. D1B mRNA was absent in olfactory bulb and mucosa. D1-like
      binding sites were detected with two distinct radioligands, in glomerular-,
      plexiform-, mitral cell- and granular layers of OB but not in olfactory mucosa.
      We thus demonstrate the previously doubtful presence of D1-like receptors in OB.
      D2 mRNAs were localized in the glomerular and granular layers of OB and in
      olfactory mucosa; lesser amounts of D3 mRNAs were found in OB glomerular and
      granular layer, but not in olfactory mucosa. No D4 mRNA was detected in either
      structure. High densities of D2-like, [125I]Iodosulpride-labelled binding sites,
      were revealed within lamina propria of olfactory mucosa, and confirmed in the
      olfactory nerve- and glomerular layers of OB. A faint but significant density of
      [3H]7-hydroxy-dipropyl-aminotetralin (OH-DPAT) labelled, D3 binding sites was
      detected in olfactory nerve- and glomerular layers of OB, but not in olfactory
      mucosa. Competition of [125I]Iodosulpride specific binding by three D2/D3
      selective drugs yielded kinetics typical of the D2 receptor subtype in olfactory
      bulb and mucosa. Olfactory nerve- and glomerular layers of OB are proved thus to
      contain a predominant contingent of D2 receptors and a minor population of D3
      receptors, while olfactory mucosa expresses only D2 receptors.

PMID- 9243345
TI  - Somatostatin and substance P-like immunoreactivity in the auditory brainstem of
      the adult rat.
AB  - The superior olivary complex (SOC) of the adult rat brainstem was studied in
      detail with regard to its innervation by neural elements showing immunoreactivity
      for two neuroactive peptides, somatostatin and substance P. Nerve fibres and
      varicosities showing positive immuno-reactivity for both peptides were
      particularly dense immediately dorsal and lateral to the lateral superior olivary
      nucleus (LSO) and dorsal to the superior paraolivary nucleus (SPN). Penetration
      of this curtain-like innervation into the SPN was limited, and the LSO showed
      only a very minor innervation by somatostatin-positive structures in its most
      medial (high frequency) lobe. Dense fibre labelling and varicosities were also
      apparent for both peptides immediately medial to the ventral and dorsal nuclei of
      the lateral lemniscus, and in the external cortex and dorsomedial zones of the
      inferior colliculus (IC). Labelled fibres and endings were also seen in the
      granule cell regions of anteroventral cochlear nucleus (AVCN) and the most
      dorsomedial parts of the dorsal cochlear nucleus (DCN). The majority of cells in
      the medial nucleus of the trapezoid body (MNTB) showed a prominent innervation by
      nerve terminals that stained positive for somatostatin only whereas the medial
      superior olivary nucleus (MSO) was devoid of label for both peptides. The ventral
      nucleus of the trapezoid body (VNTB) showed sparse but significant innervation by
      both somatostatin and substance P-positive structures. Hence the VNTB was the
      only defined nucleus of the SOC to show a significant substance P-positive
      innervation. Neuronal somata immuno-reactive for somatostatin were found in
      anteroventral and posteroventral cochlear nuclei (AVCN and PVCN) and the A5 and
      A7 cell groups adjacent to the LSO and the VNLL and DNLL and in all subdivisions
      of the inferior colliculus (IC). Somata showing only faint immunoreactivity for
      substance P were found in the VNLL, AVCN and PVCN. These results suggest a
      potential role for both peptides in auditory signal processing in the adult rat
      brain.

PMID- 9243347
TI  - Carotenoids and retinoids: a review of research, clinical, and public health
      applications.
AB  - Traditionally, the carotenoids and retinoids have been regarded as dietary
      sources of vitamin A and have been evaluated regarding their respective
      physiologic roles in vision, growth, immune system integrity, and prevention of
      vitamin A deficiency. In the 1990s, however, vitamin A deficiency is no longer
      widespread in Western countries. Therefore, the role of carotenoids and retinoids
      is evolving to encompass treatment and prevention of conditions such as cancer
      and cardiovascular disease, which are prevalent in Western societies. This review
      summarizes current research concerning the therapeutic utility of vitamin A and
      its analogues and their roles in the prevention of cancer and cardiovascular
      disease.

PMID- 9243346
TI  - Enrichment of glutamate-like immunoreactivity in the retinotectal terminals of
      the viper Vipera aspis: an electron microscope quantitative immunogold study.
AB  - A post-embedding immunogold study was carried out to estimate the
      immunoreactivity to glutamate in retinal terminals, P axon terminals and
      dendrites containing synaptic vesicles in the superficial layers of the optic
      tectum of Vipera. Retinal terminals, identified following either intraocular
      injection of tritiated proline, horseradish peroxidase (HRP) or short-term
      survivals after retinal ablation, were observed to be highly glutamate
      immunoreactive. A detailed quantitative analysis showed that about 50% of
      glutamate immunoreactivity was localized over the synaptic vesicles, 35.8% over
      mitochondria and 14.2% over the axoplasmic matrix. The close association of
      immunoreactivity with the synaptic vesicles could indicate that Vipera retino
      tectal terminals may use glutamate as their neurotransmitter. P axon terminals
      and dendrites containing synaptic vesicles, strongly gamma-aminobutyric (GABA)
      immunoreactive, were shown to be also moderately glutamate-immunoreactive, but
      two to three times less than retinal terminals. Moreover, in P axon terminals,
      the glutamate immunoreactivity was denser over mitochondria than over synaptic
      vesicles, possibly reflecting the 'metabolic' pool of glutamate, which serves as
      a precursor in the formation of GABA.

PMID- 9243348
TI  - Visual symbolization as a learning tool: teaching pharmacology to international
      audiences.
AB  - Medieval and Renaissance teaching techniques used linkage between course content
      and tangentially related visual symbols to reinforce lectures. This technique was
      adopted in teaching pharmacologic principles of addiction to international
      audiences. It produced significant results with non-English-speaking audiences
      using concurrent or consecutive translation. This technique may be useful for non
      English-speaking audiences because of enhancement of all three areas of memory:
      attention, storage, and retrieval.

PMID- 9243349
TI  - Pharmacokinetics and pharmacodynamics of 9-cis-retinoic acid in healthy men.
AB  - A double-blind, placebo-controlled, randomized study using single ascending oral
      doses of 5 mg, 15 mg, 40 mg, 80 mg, and 150 mg of 9-cis-retinoic acid was
      performed to assess the single-dose pharmacokinetics, tolerability, and
      pharmacodynamic effects of 9-cis-retinoic acid in healthy men. Forty participants
      received treatment (six taking the active treatment and two taking placebo for
      each dose level). The pharmacokinetics of 9-cis-retinoic acid were linear over
      the dose range studied. Peak plasma concentrations were achieved within 3 to 4
      hours on average. The half-life was in the range of 1.3 to 2.4 hours. Metabolism
      was the major pathway of elimination. 4-Oxo-9-cis-retinoic acid, one of four
      metabolites measured, which included all-trans-retinoic acid and 13-cis-retinoic
      acid, was the main metabolite in plasma, achieving peak plasma levels of 41% to
      83% of those of 9-cis-retinoic acid. Dose-/concentration-dependent reductions of
      retinol in plasma, with a maximum of 30% from baseline, were observed 24 hours
      after administration. Baseline levels were recovered after 5 days. Concentrations
      of retinol binding protein remained unchanged. Overall, the drug was well
      tolerated at all dose levels. Adverse events observed were consistent with
      findings of other retinoids (all-trans-retinoic acid and 13-cis-retinoic acid)
      and included headache and xeroderma at high dose levels.

PMID- 9243350
TI  - Comparative pharmacokinetics and renal effects of cyclosporin A and cyclosporin G
      in renal allograft recipients.
AB  - Cyclosporin G (CSG) has produced less nephrotoxicity than cyclosporin A (CSA) at
      equivalent doses in animal models. Conflicting results have been reported
      concerning differences in the pharmacokinetics of CSA and CSG in preclinical
      studies, and no data exist regarding the effect of steady-state oral
      administration of CSG on renal function in transplant patients or CSG-induced
      release of endothelin and nitric oxide (NO) in vivo. The objective of the study
      was to examine steady-state pharmacokinetic profiles of adult renal allograft
      recipients receiving CSA and CSG in relation to concentrations of endothelin-1
      and NO2/NO3 in urine and plasma, creatinine clearance (Clcr), and urinary
      excretion of N-acetyl-beta-D-glucosaminidase (NAG) 9 months after
      transplantation. Concentrations of CSA and CSG were measured in whole blood over
      a 12-hour dose interval by both a monoclonal and polyclonal fluorescence
      polarization radioimmunoassay for CSA. A metabolite fraction was defined as the
      numerical difference between the levels obtained at each time point by both
      assays. Patient groups were defined as follows: group 1: initial CSA (n = 6);
      group 2: initial CSG (n = 7); group 3: five of the seven patients in group 2
      taking CSG subsequently undergoing conversion to CSA; group 4: the same five
      patients in group 3 restudied 1 month after 1:1 dosage conversion to CSA; and
      group 5: CSA groups 1 and 4 combined (n = 11). In group 1, the metabolite
      fraction accounted for 32% to 54% of the total measurable drug concentration at
      each time point, whereas in group 2, the metabolite fraction accounted for at
      most 10% to 15% of the total drug levels measurable by polyclonal fluorescence
      polarization radioimmunoassay. Although there were no significant differences in
      any of the mean pharmacokinetic parameters between groups using monoclonal
      fluorescence polarization radioimmunoassay, the normalized area under the
      concentration-time curve (NAUC) value was less in four of five patients after
      conversion from CSG to CSA, with a more variable and delayed time to reach peak
      concentration (tmax) but equivalent apparent oral clearance (Clpa) values. Clcr
      was found to change significantly with time in groups 1 and 5 but not in group 2,
      with CSA producing a more profound and sustained decrease than CSG. Endothelin-1
      and NO2/NO3 levels in plasma and urine remained relatively constant after
      administration of both CSA and CSG, and there were no significant differences
      between groups 3 and 4 regarding mean endothelin-1 and NO2/NO3 concentrations in
      plasma, urinary release of endothelin-1 and NO2/NO3, and mean AUC of endothelin-1
      and AUC of NO2/NO3. However, monoclonal NAUC correlated significantly with total
      urinary endothelin-1 within CSA groups 1 and 5 but not within CSG group 2.
      Metabolite NAUC correlated significantly with total urinary NAG within CSA group
      1. Although limited by the small number of patients, this study suggests that 1)
      CSG may produce less of a reduction in Clcr over time after oral administration
      at steady state than does CSA, and 2) this beneficial effect of CSG may be in
      part due to decreased intrarenal release of endothelin-1, as urinary excretion of
      endothelin-1 seemed to correlate better with CSA than with CSG exposure.

PMID- 9243351
TI  - Pharmacokinetics of the liver-specific contrast agent Gd-EOB-DTPA in relation to
      contrast-enhanced liver imaging in humans.
AB  - This study was performed to evaluate the effect of dose on the pharmacokinetics
      and efficacy of the gadolinium-based contrast medium gadoxetic acid, disodium,
      [gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6, 9
      triazaundecandioic acid-disodium salt] (Gd-EOB-DTPA) as a liver-specific
      hepatobiliary contrast medium for computed tomography. Pharmacokinetics in serum
      and the pattern of elimination were investigated in 18 healthy volunteers up to 6
      days after a 10-minute infusion of 0.2 mmol, 0.35 mmol, and 0.5 mmol of
      gadolinium per kilogram of body weight. Pharmacokinetic behavior was compared
      with the compute tomographic attenuation data in the liver parenchyma after the
      same doses in patients. Urinary and fecal excretion accounted for approximately
      equal portions of the administered dose. The degree of renal elimination
      increased with increasing doses, whereas renal clearance and half-life from urine
      data were not affected by dose. Dose-normalized area under the concentration-time
      curve was significantly increased with increasing doses indicating saturation in
      liver uptake for the highest dose. This finding was in agreement with the
      measured net increase in liver attenuation by computed tomography. Hepatic
      disposition revealed slight saturation phenomena for the highest dose (0.5 mmol
      gadolinium/kg). Nevertheless, this dose resulted in sufficient uptake by human
      liver, allowing for computed tomographic imaging.

PMID- 9243352
TI  - Inhibition of platelet monoamine oxidase type B by selegiline.
AB  - Selegiline is an irreversible inhibitor of monoamine oxidase type B (MAO-B). No
      comparative data are available on the MAO-B inhibition caused by orally and
      intravenously administered selegiline. This study aimed to clarify this matter
      and to investigate the dose-response of MAO inhibition caused by orally
      administered selegiline. Sixteen healthy volunteers were given selegiline as a
      single intravenous dose (0.5 mg) and in three low oral doses (0.5 mg, 1.0 mg, and
      1.5 mg) in an open-label randomized crossover trial. The MAO-B inhibition after
      the 0.5-mg intravenous dose was 79.6 +/- 15.1%. The dose-response of the three
      oral doses causing MAO-B inhibition was logistic. To check whether this equation
      could be applied to higher doses, eight of the volunteers were given 5-mg and 10
      mg oral doses. The MAO-B inhibition after these doses (84.9 +/- 11.9% and 95.6 +/
      4.5, respectively) fitted well with the logistic model. With this equation
      obtained, it was calculated that a 3.4-mg oral dose of selegiline would be needed
      to obtain the same degree of MAO-B inhibition as after the intravenous dose of
      0.5 mg. Therefore, the ratio of MAO-B inhibitory potential of intravenously and
      orally given selegiline is approximately 7 to 1, which fits well with the low
      bioavailability of the drug after oral administration.

PMID- 9243353
TI  - Desmethylselegiline, a metabolite of selegiline, is an irreversible inhibitor of
      monoamine oxidase type B in humans.
AB  - Selegiline, an irreversible and selective inhibitor of monoamine oxidase type B
      (MAO-B), is metabolized into desmethylselegiline, levomethamphetamine, and
      levoamphetamine. In animal experiments, desmethylselegiline also has been shown
      to be an irreversible inhibitor of MAO-B. This study investigated the inhibitory
      potential of MAO-B and the pharmacokinetics of desmethylselegiline in humans. A
      double-blind, crossover trial was performed to compare the effects of a single
      dose (10 mg) of selegiline or desmethylselegiline on MAO-B platelet activity. The
      urinary excretion of phenylethylamine, which is considered to be a parameter of
      MAO-B inhibition, also was measured. The concentrations of selegiline,
      desmethylselegiline, and their metabolites were measured in plasma after
      administration of the two compounds. Ten healthy volunteers participated in the
      study. There was a clear inhibition of platelet MAO-B by both compounds.
      Desmethylselegiline caused a 63.7 +/- 12.7% inhibition of platelet MAO-B compared
      with 96.4 +/- 3.9% caused by selegiline. The maximal inhibition by
      desmethylselegiline was reached significantly later after desmethylselegiline
      (time to reach maximal inhibition [tmax], 27 +/- 20 hours) than after selegiline
      administration (tmax, 1.4 +/- 1.4 hours). The platelet MAO-B activity returned to
      baseline levels within 2 weeks, thus reflecting the irreversible nature of the
      inhibition by both compounds. The cumulative 48-hour excretion of
      phenylethylamine was 33% lower after desmethylselegiline than after selegiline
      administration. All three major metabolites of selegiline could be detected in
      plasma after selegiline administration. Levoamphetamine was the only metabolite
      of desmethylselegiline. The area under the concentration-time curve from time 0
      to 24 hours (AUC0-24) of desmethylselegiline was 33 times higher than that of
      selegiline, suggesting a better bioavailability of desmethylselegiline.
      Desmethylselegiline is an orally active, irreversible inhibitor of MAO-B and
      could possibly be used to treat Parkinson's disease in the same way as
      selegiline.

PMID- 9243354
TI  - Population pharmacokinetics of intravenous amiodarone and comparison with two
      stage pharmacokinetic analysis.
AB  - The disposition of amiodarone, an antiarrhythmic agent was evaluated after a
      single intravenous infusion (5 mg/kg over 15 minutes) in patients of various ages
      and with various degrees of renal function and left ventricular function. The
      plasma concentration-time data were obtained from three clinical studies with
      similar protocols. The data were analyzed by nonlinear mixed-effects modeling
      (NONMEM) to estimate the population pharmacokinetic parameters of amiodarone and
      to determine the significant demographic covariates affecting these parameters.
      The pharmacokinetic parameters of amiodarone (weight-corrected) also were
      calculated using two-stage analysis and were compared with the results obtained
      from the mixed-effects analysis. The population plasma concentration-time profile
      of amiodarone was best described by a four-compartment model. Demographic
      covariates (i.e., creatinine clearance and ejection fraction) did not improve the
      final pharmacostatistical model significantly. The results from the two-stage
      analysis showed no significant relationship between amiodarone pharmacokinetic
      parameters and age, gender, renal function, or ejection fraction. The results
      from one study, however, demonstrated that advanced age (> or = 65 years)
      resulted in reduced amiodarone clearance coupled with a prolonged elimination
      half-life. No such correlation was detected with NONMEM analysis, which may be
      partly attributable to the small number of elderly patients. Overall, the results
      from NONMEM analysis validated the results obtained from the two-stage analysis.

PMID- 9243355
TI  - Pharmacokinetics of mesna and dimesna after simultaneous intravenous bolus and
      infusion administration in patients undergoing bone marrow transplantation.
AB  - This study was undertaken to examine the pharmacokinetics of mesna and its dimer
      form, dimesna, in the plasma and urine of patients undergoing bone marrow
      transplantation who received 130 mg/kg of mesna divided intravenously into a 30
      mg/kg bolus dose followed immediately by 100 mg/kg infused over 12 hours for
      uroprotection. The relationship between and urinary excretion of mesna and
      dimesna also was examined by comparing the data obtained in patients who
      developed hemorrhagic cystitis versus those who did not. Blood and urine samples
      were collected at different time intervals after administration, and the plasma
      or urine was analyzed by liquid chromatography with electrochemical detection.
      Dimesna was analyzed in these samples after reduction back to mesna with sodium
      borohydride. The concentration-time data of mesna exhibited the characteristics
      of the two-compartment model well, and the mean +/-SD values of the distributive
      phase half-life (t1/2 alpha), postdistributive phase half-life (t1/2 beta),
      volume of distribution of the central compartment (Vdc), volume of distribution
      at steady state (Vdss), volume of distribution during the postdistributive phase
      (Vd beta), total clearance (Cl), and mean residence time (MRT) observed were 0.12
      +/- 0.15 hours, 2.12 +/- 1.61 hours, 0.324 +/- 0.336 L/kg, 1.09 +/- 1.18 L/kg,
      2.09 +/- 3.0 L/kg, 0.755 +/- 0.507 L/hr.kg, and 6.77 +/- 0.72 hours,
      respectively. The mean +/-SD values of t1/2 and MRT of dimesna were 1.29 +/- 0.6
      hours and 6.68 +/- 1.05 hours, respectively, and the ratio of the area under the
      concentration-time curve (AUC) of mesna to that of dimesna was 1.21 +/- 0.57. The
      fractions of dose excreted in urine in the form of mesna and dimesna in 20 hours
      (fu) were 0.361 +/- 0.15 and 0.482 +/- 0.25, and the renal clearance (ClR) values
      were 0.244 +/- 0.201 L/hr.kg and 0.157 +/- 0.156 L/hr.kg, respectively. The
      urinary excretion of mesna in these patients was higher than that required for
      uroprotection for the whole duration of infusion, and there was no significant
      difference in the pharmacokinetics of mesna between patients who developed
      hemorrhagic cystitis and those who did not. This was not the case with dimesna,
      in which patients with hemorrhagic cystitis excreted in urine less than 50% of
      the amount of dimesna excreted by those without hemorrhagic cystitis.

PMID- 9243356
TI  - Dose proportionality of cisatracurium.
AB  - The dose proportionality of cisatracurium pharmacokinetics was assessed using a
      population approach by incorporating the collection of sparse blood samples from
      patients in clinical trials. Plasma concentration-time data from 131 patients
      with limited concentration-time data and 38 patients with full sampling were
      pooled and analyzed using nonlinear mixed-effects modeling (NONMEM). Dose
      proportionality was assessed using dichotomous parameterization and a linear
      model. The population pharmacokinetic approach revealed that the pharmacokinetics
      of cisatracurium are independent of dose between 0.1 mg/kg and 0.4 mg/kg, as was
      expected based on the importance of Hofmann elimination, a chemical process
      dependent on pH and temperature.

PMID- 9243357
TI  - Bioavailability of oral cyclosporine in healthy Mexican volunteers: evidence for
      interethnic variability.
AB  - The existence of population variations in cyclosporine pharmacokinetics could be
      expected, as this drug, similar to nifedipine, is biotransformed by cytochrome P
      450 subfamily 3A4, and the existence of interethnic variability in nifedipine
      disposition has been demonstrated previously. The bioavailability of oral
      cyclosporine was studied in 23 healthy Mexican volunteers receiving 7.5-mg/kg
      doses of cyclosporine. Blood samples were drawn over 24 hours, and concentration
      of cyclosporine in whole blood was determined by a radioimmunoassay using
      monoclonal antibodies specific for the unchanged drug. The bioavailability of
      cyclosporine exhibited wide interindividual variability. Maximum concentration
      (Cmax) ranged from 528 ng/mL to 2,689 ng/mL, area under the concentration-time
      curve (AUC) ranged from 6,550 ng.hr/mL to 18,562 ng.hr/mL, and time to reach Cmax
      (tmax) ranged from 1 to 8 hours. Half-life (t1/2) exhibited less important
      variations, ranging from 4.4 to 9.1 hours. The bioavailability of oral
      cyclosporine in Mexicans was higher than that reported for white populations
      under similar conditions. The present results suggest the existence of
      interethnic variability in the pharmacokinetics of cyclosporine, as is the case
      with nifedipine.

PMID- 9243358
TI  - Interpatient variability: genetic predisposition and other genetic factors.
AB  - Polymorphisms and other genetic factors related to enzymes metabolizing drugs and
      xenobiotic chemicals are well known. This article focuses on selected molecular
      mechanisms and introduces some of the clinical implications arising from
      genetically determined interpatient variability or expression in some of these
      enzymes. Selected are the polymorphic enzymes of cytochromes P-450 (CYP) as
      examples of phase I enzymes and methyl transferases, n-acetyl transferases, and
      glutathione-s-transferases as examples of phase II enzymes. The polymorphism
      surrounding arylhydrocarbon hydroxylase induction is briefly described. Phase I
      enzymatic reactions are predominantly oxidative, whereas phase II reactions often
      couple with the byproducts of phase I. Overall, in poor metabolizers, whether
      phase I or phase II, there is limited metabolism in most patients unless another
      major metabolic pathway involving other enzymes exists. Drug metabolism also
      depends on whether the parent compound is a prodrug that forms an active
      metabolite, and poor metabolizers under this condition will form only trace
      amounts of an active compound. Therefore, the clinical significance of genetic
      polymorphisms and other genetic factors may be related to substrate, metabolite,
      or the major elimination pathway.

PMID- 9243359
TI  - Potentiation of mivacurium by rocuronium is age- and time-dependent: a study in
      children, adolescents, and young and elderly adults.
AB  - Potentiation occurs when the steroidal muscle relaxant, rocuronium, is
      coadministered with the benzylisoquinolinium relaxant, mivacurium. The effect of
      time and age on this interaction was evaluated in four predetermined groups:
      children, adolescents, young adults, and elderly adults (15 per group) by
      monitoring the ulnar nerve-evoked force of contraction of the adductor pollicis
      (twitch response). During recovery from paralysis induced by 800 micrograms/kg of
      rocuronium, an infusion of mivacurium was started and maintained for at least 90
      minutes to retain the twitch response at 1% to 9% of baseline tension (95 +/- 4%
      paralysis). Rocuronium at 600 micrograms/kg induced greater than 95% paralysis in
      57 of the 60 patients within 2.2 +/- 0.4 (mean +/- SE) minutes. The period of
      recovery from rocuronium-induced paralysis to 5% of baseline twitch height was
      longest in the elderly (30.1 +/- 2.9 minutes) and shortest in the adolescents
      (16.5 +/- 2.4 minutes). The mivacurium infusion requirements to maintain 95 +/-
      4% paralysis was highest in children and progressively increased with time. In
      young and elderly adults, the infusion rates remained lower than that of children
      and did not change with time. The incidence of satisfactory spontaneous recovery
      within 20 minutes (train-of-four ratio > 75%) was the highest in children,
      followed by adolescents and young adults, and was least in the elderly. The
      residual neuromuscular effect of rocuronium on the subsequent mivacurium infusion
      was most pronounced in the elderly, followed by young adults, then adolescents,
      and was least in children.

PMID- 9243360
TI  - The Revised European-American Classification of Lymphoid Neoplasms (REAL): a new
      perspective for the classification of cutaneous lymphomas.
AB  - Differing classification schemes for malignant lymphomas have been used in Europe
      and the United States. Attempts to translate between the principle
      classifications have been unsuccessful and historically it has been difficult to
      arrive at an unified approach. In addition, many new lymphoma entities have been
      recognized in recent years that are not delineated in any of the existing
      classification schemes. To provide a unified international basis for clinical and
      investigative work in this field, in 1994 the International Lymphoma Study Group
      (ILSG) proposed a new classification termed Revised European-American
      Classification of Lymphoid Neoplasms (REAL). This review discusses the REAL
      classification, especially as it pertains to cutaneous lymphomas, and provides
      insight into the clinicopathologic features of lymphoproliferative disease
      involving the skin. The premise of the REAL classification is that a
      classification scheme should be based on the delineation of disease entities,
      utilizing pathologic, immunophenotypic, genetic, and clinical features.
      Therefore, if cutaneous involvement is an integral aspect of any lymphoma
      subtype, this clinical information is included in the definition of that
      neoplasm. We conclude that the principles of the REAL classification are
      applicable to cutaneous lymphomas, as well as lymphomas involving other anatomic
      sites.

PMID- 9243361
TI  - CD44 variant expression in cutaneous T-cell lymphoma.
AB  - Expression of the lymphocyte homing receptor CD44 and its splice variants have
      been linked to tumour dissemination and poor prognosis in non-Hodgkin's lymphoma.
      Specifically, the in vitro expression of variant exon V6 confers metastatic
      potential in rat pancreatic carcinoma cell lines. In this study, we investigated
      the expression of CD44 splice variants in cutaneous T-cell lymphomas, including
      patients with mycosis fungoides (MF), Sezary syndrome (SS), large-cell anaplastic
      lymphoma (LCAL) and HTLV1-associated cutaneous lymphoma. In addition, 4 involved
      lymph nodes from 2 patients with MF and 1 patient with SS were examined.
      Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also
      studied. Immunohistochemistry was performed using a panel of monoclonal
      antibodies, including those with specificity for CD44H (standard isoform) and
      variant exons V3, V6 and V8-9. Normal epidermal keratinocytes were consistently
      CD44H and CD44 V3, V6 and V8-9 positive. In all the different clinicopathological
      subtypes and stages of cutaneous T-cell lymphomas, including involved lymph
      nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6
      negative. CD44 V8-9 was expressed on a majority of tumour cells in 2/5 LCAL and
      on occasional tumour cells in 2/5 LCAL. Occasional V8-9 positive tumour cells
      were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples
      from 2 patients with tumour-stage MF, CD44 V8-9 expression was found on a small
      percentage of atypical mononuclear cells. Scattered V8-9 positive dermal
      mononuclear cells were present in sections of lichen planus and psoriasis. We
      have found no evidence to suggest that the metastasis-associated CD44 variant
      exon (V6) is expressed in cutaneous T-cell lymphoma, or that CD44H expression is
      associated with an adverse prognostic group. It is not clear whether the strong
      expression of CD44 V8-9 in 2 patients with CD30 positive LCAL reflects activation
      status or metastatic potential.

PMID- 9243362
TI  - Cytoplasmic microtubules in two different mouse melanoma cell lines: a
      qualitative and quantitative analysis using confocal laser scanning microscopy
      and computer-assisted image analysis.
AB  - The microtubular system as one part of the cellular cytoskeleton is not only
      necessary for mitotic activity of malignant cells but also for invading
      neighboring tissues and for the formation of distant metastases. In the present
      study, the amount and distribution of tubulin in two murine melanoma cell lines
      (K1735-M2: high metastatic clone; K1735-c116: low metastatic clone) were
      determined quantitatively using an indirect immunofluorescence technique,
      confocal laser scanning microscopy (CLSM) and computer-assisted image analysis.
      Additionally, qualitative and quantitative changes after application of the
      microtubule-inhibitor nocodazole were investigated. Quantitative analysis showed
      a significant difference between the high and low metastatic cell line for the
      parameter TEXTURE, indicating a finer structured network within the high
      metastatic cells. After treatment with nocodazole the parameters TEXTURE and
      DENSITY were reduced, suggesting a decrease of assembled tubulin and a less
      delicate structure of the remaining microtubules. Our study shows that CLSM
      combined with computer-assisted image analysis provides a new method to examine
      quantitative variations of the cytoskeleton possibly related to cell function.

PMID- 9243363
TI  - Differential proliferation of endothelial cells and keratinocytes in psoriasis
      and spongiotic dermatitis.
AB  - This study used MIB-1 monoclonal antibody to quantify the proliferating
      keratinocytes and endothelial cells and their proliferation fractions in cases of
      normal skin, acute and established plaque psoriasis, and acute and chronic
      spongiotic dermatitis. The number and the proliferation fraction of MIB-1
      positive cells were higher in psoriatic and chronic spongiotic lesions than in
      normal skin (p < 0.05). Established plaque psoriasis had a higher number of
      proliferating keratinocytes and a higher keratinocytic proliferation fraction
      than did acute psoriasis (p < 0.05). The number of proliferating endothelial
      cells decreased as acute psoriatic lesion became chronic, but the number in acute
      spongiotic lesion increased as it became chronic. The endothelial proliferation
      fraction was higher in acute psoriasis than in established plaque psoriasis (p <
      0.05). The ratio of keratinocytic proliferation fraction to endothelial cell
      proliferation fraction of the psoriatic and spongiotic lesions suggested the
      presence of different reaction patterns to inflammation in psoriasis and
      spongiotic dermatitis.

PMID- 9243364
TI  - Differences in tumor microvessel density between squamous cell carcinomas and
      basal cell carcinomas may relate to their different biologic behavior.
AB  - Tumor microvessel density (TMVD) has been recognized as an important indicator
      for the metastatic risk in certain tumors. The purpose of this study was to
      analyse whether there is an association of TMVD in epithelial neoplasms of the
      skin with their clinical behavior. Paraffin sections of keratoacanthomas (KA, n =
      10), squamous cell carcinomas (SCC, n = 9), nodular (nod-BCC, n = 13), and
      sclerosing (scl-BCC, n = 12) basal cell carcinomas were immunohistochemically
      stained for factor-VIII-related antigen and TMVD was determined. In all SCC, KA
      and nod-BCC, TMVD significantly exceeded perilesional skin microvessel density
      (PSMVD) (SCC:TMVD/PSMVD = 20.54:11.25, p < 0.0001; KA:TMVD/PSMVD = 20.90:12.17, p
      < 0.0001; nod-BCC:TMVD/PSMVD = 16.77:13.34, p = 0.03). In contrast, no
      significant difference between TMVD and PSMVD was found in scl-BCC (15.44:12.86,
      p = 0.22). TMVD was significantly higher in SCC and KA compared to nod-BCC (p =
      0.036 and 0.006, respectively). Our data demonstrate that SCC and KA are highly
      vascularized tumors. The fact that TMVD does not differ significantly between SCC
      and KA (p = 0.80) suggests that MVD is not an indicator for the metastatic risk
      or aggressive growth behavior of epithelial skin tumors. The finding that MVD in
      both nod- and scl-BCC is significantly lower than in SCC and KA, might at least
      in part explain the slow growth of BCC.

PMID- 9243365
TI  - Immunohistochemical analysis of keratin expression in clear cell syringoma. A
      comparative study with conventional syringoma.
AB  - Immunophenotypes, especially expression of cytokeratins, in 9 cases of clear cell
      syringoma were examined using antibodies against epithelial membrane antigen
      (EMA), and 17 kinds of monoclonal anti-keratin antibodies to investigate its
      histogenesis. In addition, 7 cases of conventional syringoma were selected for
      parallel assessment. Conventional syringoma expressed CK1 and CK10, which exists
      in the acrosyringium and the transitional portion between the acrosyringium and
      the dermal duct. Based on immunostaining with RCK102 and 35 beta H11, syringoma
      was thought to express CK5. Because expression of CK5 was observed in the basal
      cells of sweat duct ridge (lower acrosyringium) and the outer cells of the dermal
      duct, but not in the acrosyringium located at upper epidermis, we speculated that
      syringoma differentiated toward the transitional portion between the
      acrosyringium and the dermal duct. A comparative study of keratin expression
      between conventional and clear cell syringoma showed that there was no difference
      in the immunoreactivities. Based on the above observations, we confirmed that
      clear cell syringoma is a metabolic variant of conventional syringoma, and
      differentiates into the transitional portion between the acrosyringium and the
      dermal duct.

PMID- 9243366
TI  - Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical case
      study shows cellular composition by CD34+ fibroblasts and factor XIIIa+
      dendrophages.
AB  - We report immunomorphologic observations on a pleomorphic hyalinizing angiectatic
      tumor of soft parts (PHAT), a rare tumor recently described by Smith, Fisher, and
      Weiss. A 2 cm skin-covered, grossly lobulated, firm, yellow-tan, focally
      hemorrhagic tumor was excised from the dorsum of a 59-year-old woman's right
      foot. It infiltrated dermis and subcutis and entrapped skin adnexae. The tumor
      microscopically resembled both a pleomorphic malignant fibrous histiocytoma and a
      neurilemoma with fascicular spindle cell pattern, pleomorphic tumor giant cells,
      and focal congeries of ectatic, fibrinous, and slightly hyalinized vessels.
      Tumour cells produced abundant reticulin but collagenous sclerosis was minimal.
      Mast cells were numerous. Pleomorphic cells, some phagocytic, had intranuclear
      vacuolar inclusions and many cells had large pale cytoplasmic globular
      inclusions. Most tumor cells expressed vimentin and CD34, including pleomorphic
      cells. Factor XIIIa stained focally 20-40% of the spindle cells. S-100 and
      cytokeratin were negative and actin and desmin stained only vessel myopericytes.
      The Ki 67 index was 3% with mostly large CD34+ cells and a few smaller FXIIIa+
      cells in the cycling fraction. We conclude that PHAT is a fibrohistiocytic tumor
      probably derived from proliferating microvascular CD34+ dendritic cells and
      FXIIIa+ dendrophage cell subsets. Possible interactions between these cell types
      deserve further study in PHAT and other fibrohistiocytic tumors.

PMID- 9243367
TI  - Giant intravenous glomus tumor.
AB  - We report a painful intravenous glomus tumor located in the right forearm of a 79
      year-old woman. The tumor originated from the wall of a vein, protruded into its
      lumen and was completely excised. The largest dimension of the tumor occluding
      the vein was 14 cm. Tumor cells were characterized immunohistochemically by the
      presence of vimentin, alpha-smooth-muscle actin, and collagen IV. Intravascular
      spread of the glomus tumor is rare and has been described in the stomach and
      subcutaneous tissue. An entirely intravenous glomus tumor has been reported only
      three times. However, a huge intravenous growth as in our case appears never to
      have been reported. A review of the intravascular cases showed that the average
      age of presentation is 61.5 years (range 40-79 years) and the most frequent
      location is the forearm. Despite this intravascular growth, there is no evidence
      of aggressive clinical behavior, recurrence or metastasis. The pathologist must
      be aware of this variant of glomus tumor to avoid misdiagnosis and unnecessary
      additional treatments.

PMID- 9243368
TI  - Cutaneous pseudosarcomatous polyp--another variant of dermal lipoma or only an
      "ancient" skin tag?

PMID- 9243369
TI  - Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in
      chronic fatigue syndrome.
AB  - Previous studies from this laboratory have demonstrated a statistically
      significant dysregulation in several key components of the 2',5'-oligoadenylate
      (2-5A) synthetase/RNase L and PKR antiviral pathways in chronic fatigue syndrome
      (CFS) (Suhadolnik et al. Clin Infect Dis 18, S96-104, 1994; Suhadolnik et al. In
      Vivo 8, 599-604, 1994). Two methodologies have been developed to further examine
      the upregulated RNase L activity in CFS. First, photoaffinity labeling of
      extracts of peripheral blood mononuclear cells (PBMC) with the azido 2-5A
      photoaffinity probe, [32P]pApAp(8-azidoA), followed by immunoprecipitation with a
      polyclonal antibody against recombinant, human 80-kDa RNase L and analysis under
      denaturing conditions. A subset of individuals with CFS was identified with only
      one 2-5A binding protein at 37 kDa, whereas in extracts of PBMC from a second
      subset of CFS PBMC and from healthy controls, photolabeled/immunoreactive 2-5A
      binding proteins were detected at 80, 42, and 37 kDa. Second, analytic gel
      permeation HPLC was completed under native conditions. Extracts of healthy
      control PBMC revealed 2-5A binding and 2-5A-dependent RNase L enzyme activity at
      80 and 42 kDa as determined by hydrolysis of poly(U)-3'-[32P]pCp. A subset of CFS
      PBMC contained 2-5A binding proteins with 2-5A-dependent RNase L enzyme activity
      at 80, 42, and 30 kDa. However, a second subset of CFS PBMC contained 2-5A
      binding and 2-5A-dependent RNase L enzyme activity only at 30 kDa. Evidence is
      provided indicating that the RNase L enzyme dysfunction in CFS is more complex
      than previously reported.

PMID- 9243370
TI  - Potentiation of interferon-induced indoleamine 2,3-dioxygenase mRNA in human
      mononuclear phagocytes by lipopolysaccharide and interleukin-1.
AB  - Previous studies have shown that interleukin-1 (IL-1) enhances interferon (IFN)
      gamma-induced indoleamine 2,3-dioxygenase (IDO) enzymatic activity in human
      monocyte-derived macrophages by increasing expression of IDO mRNA. The objectives
      of this study were to see if IL-1 also enhances IFN-beta-induced IDO activity by
      increasing specific mRNA expression and to determine if lipopolysaccharide (LPS)
      enhances IFN-induced IDO activity in a similar manner. Macrophages were treated
      with combinations of IFN-beta or IFN-gamma as inducer and LPS or IL-1 as
      potentiator. After 48 h, IDO mRNA expression was assessed by RT-PCR, and IDO
      activity was determined by HPLC. LPS alone induced IDO mRNA expression and also
      increased IDO mRNA expression induced by either type of IFN. Furthermore, IL-1
      enhanced IFN-beta-induced IDO mRNA expression. When IDO mRNA was assessed 6 h
      after treatment, mRNA was detected at concentrations of IFNs or potentiator or
      both in which enzymatic activity at 48 h was undetectable. Thus, although the
      mechanism of potentiation of IFN-induced IDO by LPS and by IL-1 involves
      increased expression of IDO mRNA, it appears that temporal differences in IDO
      mRNA expression are also important.

PMID- 9243371
TI  - Protection of hematopoietic progenitors from ultraviolet C by interleukin-1 and
      tumor necrosis factor-alpha.
AB  - Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can protect
      hematopoietic progenitors from the toxicity of 4-hydroperoxycyclophosphamide (4
      HC) and gamma radiation. We hypothesize that IL-1 and TNF-alpha may be inducing a
      universal stress reaction in hematopoietic progenitors. In this study, we
      examined their protective effects against ultraviolet C (UVC) compared with that
      seen against 4-HC using colony formation assays and flow cytometric analysis. We
      demonstrated that 20 h preincubation with IL-1 or TNF-alpha or both protected
      normal hematopoietic colony-forming cells (CFCs) from UVC. Colony formation
      assays and flow cytometric analysis of the cells protected from either 4-HC or
      UVC revealed that similar proportions of hematopoietic progenitors are protected
      in the IL-1 and TNF-alpha group in comparison to control. Furthermore, at least
      20 h of preincubation with the two cytokines was needed for optimal protection.
      The addition of 2 micrograms/ml cycloheximide, a protein synthesis inhibitor,
      during the 20 h preincubation completely abolished the protection observed for
      CFCs. In conclusion, IL-1 and TNF-alpha can protect normal hematopoietic
      progenitors from UVC as well as from 4-HC and gamma radiation, and, therefore, a
      global response to DNA damaging treatments induced by IL-1 and TNF-alpha needs to
      be further investigated.

PMID- 9243372
TI  - Neutralization of endogenous interferon-beta increases the efficiency of
      adenoviral vector-mediated gene transduction.
AB  - One reason for low transduction efficiency and, hence, the inefficiency of gene
      therapy using adenoviral vectors may be the natural antiviral defense mechanisms
      of hosts. In this study, we investigated the effects of endogenous interferon
      beta (IFN-beta) on gene transduction by adenoviral vectors. Infection of murine
      macrophages with Ad5CMV-LacZ produced increased expression of endogenous IFN
      beta. Neutralization with anti-IFN-beta antibody (but not control immunoglobulin)
      during infection with the vector enhanced expression of LacZ. In contrast, IFN
      beta gene expression was not detected in readily transduced NIH 3T3 cells, and
      the transduction efficiency of NIH 3T3 cells was unaffected by the antibody. LacZ
      gene expression in NIH 3T3 cells was decreased when cocultured with macrophages
      or in the presence of exogenous IFN-beta. The addition of the anti-IFN-beta
      antibody reversed this inhibition. These results demonstrate that IFN-beta
      mediated cellular antiviral mechanisms are a barrier to gene transduction by
      adenoviral vectors.

PMID- 9243373
TI  - Interferon-associated thyroid dysfunction in anti-D-related chronic hepatitis C.
AB  - To assess the frequency and nature of thyroid abnormality in association with
      interferon (IFN) therapy alone and in combination with ribavirin, 19 patients
      receiving IFN therapy for hepatitis C virus (HCV)-induced liver disease had
      thyroid function tests assessed on a monthly basis. Group I (n = 9) patients
      received 5 million U of IFN s.c. daily for 2 weeks, followed by 3 million U three
      times per week for 6 months. Group II (n = 10) patients received 3 million U IFN
      s.c. three times per week together with ribavirin 400 mg twice daily orally for 6
      months. Five of 19 patients (26.3%) developed thyroid abnormalities, 3 (33.3%) in
      group I and 2 (20%) in group II. Three patients developed thyroid function tests
      consistent with hyperactivity, and 2 of these normalized on cessation of IFN
      therapy. One patient continued on IFN but remained clinically euthyroid with
      antithyroid treatment. Two patients developed thyroiditis and required thyroid
      supplementation. (One of the 2 had pretreatment antimicrosomal thyroid antibodies
      and a positive family history of thyroid disease.) Of the 3 patients with HCV
      type 1b, 1 had pretreatment thyroid antibodies, and all 3 had antibodies during
      IFN therapy. Neither of the 2 patients with genotype 3 had pre-IFN or post-IFN
      thyroid antibodies. Patients on IFN therapy need regular thyroid function
      testing. The frequency of abnormal thyroid tests may be dose related. HCV
      genotype may influence the development of thyroid antibodies.

PMID- 9243374
TI  - Role of glucocorticoid in the upregulation of type I interleukin-1 receptor mRNA
      expression in hepatocytes of endotoxin-administrated mice.
AB  - The interleukin-1 (IL-1) signal is transduced through type I IL-1 receptor (IL
      1RI). We have recently reported that lipopolysaccharide (LPS) upregulated IL-1RI
      mRNA expression in mouse liver in vivo and that IL-1 and IL-6 directly
      upregulated IL-1RI mRNA expression in primary cultured mouse hepatocytes.
      Glucocorticoid (GC) has been reported to increase IL-1 binding to the cell
      surface and the expression level of IL-1R mRNA in a variety of cell types. As
      serum GC level is elevated in an inflammatory response, we evaluated the role of
      GC in LPS-induced upregulation of IL-1RI mRNA in the mouse liver. When LPS was
      administered to adrenalectomized (ADX) mice, IL-1RI mRNA was upregulated at a
      level comparable to those of untreated or sham-operated mice. A high dose of
      dexamethasone (Dex), however, caused upregulation of the mRNA. When primary
      cultured mouse hepatocytes were treated with Dex, only a weak upregulation of IL
      1RI mRNA was observed. However, Dex in combination with IL-1 or IL-6 markedly
      enhanced the IL-1RI mRNA expression. A marked upregulation of the mRNA was also
      induced by treatment with a combination of IL-1 and IL-6 in the absence of Dex,
      reflecting the observation in ADX mice. These results suggest that the
      upregulation of IL-1RI mRNA in response to LPS is induced by the interaction of
      IL-1 and IL-6 and that GC augments their effect.

PMID- 9243375
TI  - Poly ICLC enhances the antimalarial activity of chloroquine against multidrug
      resistant Plasmodium yoelii nigeriensis in mice.
AB  - Swiss mice infected with multidrug-resistant Plasmodium yoelii nigeriensis were
      treated with polyinosinic-polycytidylic acid stabilized with polylysine and
      carboxymethyl cellulose (Poly ICLC), a potent interferon (IFN) inducer and immune
      enhancer, in combination with chloroquine (CQ), which completely eliminated the
      malaria parasite from these animals. The enhancement of the antimalarial activity
      of poly ICLC was found to be completely reversed by the cytochrome P-450 inducer,
      phenobarbitone. No effect of Nw nitro-L-arginine (NLA), an inhibitor of nitric
      oxide, was seen on the enhancement of the antimalarial activity of CQ by Poly
      ICLC. These results suggest the possible involvement of cytochrome P-450 enzyme
      mediated mechanism in the enhancement of the antimalarial activity of CQ by Poly
      ICLC.

PMID- 9243377
TI  - Nomenclature of interferon receptors and interferon-delta.

PMID- 9243376
TI  - Upregulation of a myristylated 74-kDa protein by interferon treatment of Daudi
      cells.
AB  - Labeling of unstimulated human Daudi B lymphoblastoid cells with exogenously
      added [3H]myristate resulted in acylation of a broad spectrum of different
      proteins, most of which are currently unknown. Among this array of labeled
      proteins, a unique 74-kDa acylated protein was induced in interferon (IFN)
      treated cells. In the present study, we defined the myristylation kinetics of
      this protein and examined the subcellular distribution before and after
      activation with IFN-alpha/beta. This acylated protein was detected only at a very
      low level in the membrane fraction of untreated cells, and its level increased 3
      4-fold by treatment with IFN. This induction occurred over a short period of time
      and was IFN-alpha/beta dose-dependent. No significant induction was observed with
      IFN-gamma. Incorporation of [3H]myristate was completely abolished by
      cycloheximide. The fatty acid associated with this protein was probably linked to
      a nascent chain through an amide linkage, as it was not released by alkaline
      hydroxylamine treatment and was identified as myristic acid by HPLC after its
      release from the polypeptide chain by acid methanolysis. In contrast to other IFN
      induced proteins, whose synthesis started at 10 h and was maintained for 20 h,
      this protein was present in the plasma membrane for a short period of time,
      between 4 and 6 h after IFN-alpha/beta treatment, and was no longer present in
      this cellular compartment. This event appears to be transient and suggests that a
      degradation or a negative regulation of transcription starts from 6-7 h after
      continuous IFN treatment. As many other myristylated proteins are implicated in
      cellular regulation, it is possible that this 74-kDa protein may have a
      regulatory role in cell proliferation and the inhibition of viral replication.

PMID- 9243378
TI  - Contrast-enhanced, K-space-centered, breath-hold MR angiography of the renal
      arteries and the abdominal aorta.
AB  - The purpose of this study was to evaluate the capability of contrast-enhanced
      breath-hold fast imaging with steady-state precession (FISP) three-dimensional MR
      angiography (MRA) to detect stenotic lesions of the abdominal aorta, the renal
      arteries, and the iliac arteries by using a K-space-centered 20-ml gadolinium
      diethylene pentaacetic acid (Gd-DTPA) bolus. Fifty patients were studied before
      conventional x-ray angiography. Contrast-enhanced breath-hold FISP three
      dimensional MRA was applied in the coronal view, centered at the renal arteries.
      Twenty ml of Gd-DTPA was used in all subjects. A test bolus was applied to
      determine the injection time for the K-space-centered bolus injection. Of 300
      segments, 284 segments were classified correctly, 11 were overestimated, and five
      were underestimated. Sensitivity was 98%, specificity was 96%, positive
      predictive value was 96%, negative predictive value was 98%, and accuracy was
      97%. Of the 50 patients studied, 43 were staged correctly. No venous overlay was
      seen in 31 patients; partial overlay was seen in 16 patients, and venous
      structure overlay obscuring arterial anatomy was found in two patients. Six of
      nine accessory renal arteries could be identified by MRA. Intraobserver
      variability was .94. This study has shown the ability of contrast-enhanced breath
      hold FISP three-dimensional MRA to detect and grade vascular lesions in the
      abdominal aorta and the renal arteries. The method may serve as a screening tool
      in the future.

PMID- 9243379
TI  - Gadolinium-enhanced breath-hold three-dimensional time-of-flight MR angiography
      of the abdominal and pelvic vessels: the value of ultrafast MP-RAGE sequences.
AB  - MR angiography (MRA) was performed in 50 consecutive subjects (mean age, 59
      years), who had been referred for abdominal MRA, on a 1.5-T superconductive unit
      that used a body phased-array coil. Three breath-hold three-dimensional sequences
      were evaluated both in phantom and clinical studies: (a) standard fast three
      dimensional gradient-echo sequence (TR = 15, TE = 6; imaging time, 32 seconds),
      (b) ultrafast three-dimensional gradient-echo sequence (TR = 8.2, TE = 3; imaging
      time, 18 seconds), and (c) ultrafast magnetization-prepared (MP) rapid
      acquisition gradient echo (RAGE) (TR = 5.8, TE = 2.9, inversion time [TI] = 20;
      imaging time, 15 seconds). The initial 30 patients were randomized into three
      groups by three separate sequences. For the remaining 20 patients, ultrafast
      gradient-echo and ultrafast MP-RAGE sequences were performed. Conventional
      angiography was performed on 36 patients. Signal measurements of the phantom and
      clinical images of the aorta, visceral branches of the aorta, iliac arteries,
      inferior vena cavae, and portal veins were performed. The overall image quality
      and background fatty tissue contrast of the vessels were rated subjectively.
      Comparison of images between MRA and conventional angiography also was performed.
      The contrast between the vessels and background fatty tissue was significantly
      higher in the ultrafast MP-RAGE sequence in both quantitative and qualitative
      analysis, and image-quality ultrafast MP-RAGE was superior to the other two
      sequences (P < .01). The aorta and iliac arteries could be visualized in all
      pulse sequences, and abnormalities of these vessels were diagnosed correctly. The
      renal artery was visualized more clearly with the two ultrafast sequences.

PMID- 9243380
TI  - MR navigator-echo monitoring of temporal changes in diaphragm position:
      implications for MR coronary angiography.
AB  - Temporal changes in respiration could influence navigator-echo (NE)-gated MR
      coronary angiography (MRCA), but systematic investigation of the effects of such
      variations and how to limit them has not been performed. We addressed these
      issues by studying the influence of time in the magnet on diaphragm position and
      respiratory patterns using NE diaphragm monitoring in volunteers and a phantom
      model. NE diaphragm monitoring was performed at .5 T in 10 subjects over a total
      period of 35 minutes. The end-expiratory position was sustained for longer (1.1
      vs .4 seconds, P < .001) and with greater position stability (SD 1.9 vs 5.9 mm, P
      = .01) than the end-inspiratory position. Drift of the end-expiratory position
      occurred over time, causing a fall in scan efficiency (44-28%, P = .01). Up-drift
      of the end-expiratory position was most common. Loss of scan efficiency was worse
      with up-drift because of loss of the end-expiratory pause from the NE window (up
      drift 10% mm-1, down-drift 7% mm-1, both P = .03). Scan efficiency also was
      reduced during sleep (to a nadir of 0%), secondary to loss of the end-expiratory
      pause, periodic breathing with oscillating end-expiratory position, and periods
      of apnea. The phantom model used actual diaphragm traces to evaluate the artifact
      resulting from diaphragm motion during acquisition. Artifact was considerably
      reduced by NE adaptive motion correction compared with NE gating alone (ghosting
      ratio 2.0 vs 2.8, P < .01). Artifact also was significantly reduced with up-drift
      if scan efficiency was maintained above 35% (P = .05). For optimal NE-gated MRCA,
      the following features are important: the NE window should be placed around the
      end-expiratory position; subjects should not sleep; scan efficiency should be
      monitored and the NE window should be repositioned if scan efficiency falls below
      35%; and adaptive motion correction should be used.

PMID- 9243381
TI  - Flow-independent angiography for peripheral vascular disease: initial in-vivo
      results.
AB  - Flow-independent angiography (FIA), an approach that isolates arterial blood
      using MR relaxation characteristics rather than flow effects, was evaluated for
      application in peripheral vascular disease (PVD). First, pilot studies were
      conducted in which FIA coronal projection images were obtained from controls and
      symptomatic patients with PVD to assess clinical utility. All control images
      corresponded to the expected leg arterial anatomy with little interference from
      deep veins (one of five) and muscle (zero of five). Superficial venous signal was
      less well suppressed in comparison to deep veins (four of five). Images of
      symptomatic patients were less consistent with difficulty suppressing muscle and
      deep venous signal in some cases and edema when present. We then compared T2
      values for muscle (T2m, tibialis anterior), arterial blood (femoral and popliteal
      arteries), and venous blood (femoral, popliteal, and saphenous veins) in controls
      (n = 8) and symptomatic patients with intermittent claudication (n = 5) or
      ischemic rest pain (n = 7). Changes in T2 measurements of various tissues
      accounted for poorer contrast in symptomatic patients. Patients with ischemic
      rest pain had significantly higher T2m compared with controls (T2m = 39.3 +/- 2.1
      (1 standard error of the mean [SEM]) versus 30.9 +/- .4, P < .01). For all
      measurements, other than saphenous vein, variances were greater in symptomatic
      patients. To realize the inherent advantages of FIA for this clinical
      application, additional work on suppression of signals from muscle, veins, and
      edema is required. One promising approach involves shifting from projection
      images to three-dimensional acquisitions for improved tissue suppression.

PMID- 9243382
TI  - Proximal coronary artery stenosis: three-dimensional MRI with fat saturation and
      navigator echo.
AB  - The purpose of this study was to compare the diagnostic value of MR angiography
      (MRA) with conventional contrast angiography in coronary artery disease. Thirty
      five patients underwent MRA and coronary angiography within 4 hours. Of these,
      three patients were investigated twice: once before and once after balloon
      angioplasty. The pulse sequence was a cardiac-triggered, single-slab, three
      dimensional gradient-echo sequence, employing a spin-echo navigator echo
      measurement to track the variation of the diaphragm during the scan. The
      following segments of the coronary arteries were included in this prospective
      study: left main coronary artery, proximal and middle left anterior descending,
      proximal and middle left circumflex, proximal and middle right coronary artery,
      and intermediate branch, if present. In total, 176 segments were classified as
      normal or having a stenosis of less than 50% and as having a stenosis of more
      than 50%. Five patients were excluded because of lack of cooperation. Over all,
      45 of 54 stenoses were detected and interpretable by MRA. Sensitivity,
      specificity, and positive and negative predictive values of MRA for detecting
      significant stenoses were 83%, 94%, 87%, and 93%, respectively. MRA identified
      significant stenoses within the major coronary arteries with a high degree of
      accuracy. Sensitivity and specificity are higher compared with exercise tests or
      scintigraphy or top of the precise localization.

PMID- 9243383
TI  - Immediate postgadolinium spoiled gradient-echo MRI for evaluating the abdominal
      aorta in the setting of abdominal MR examination.
AB  - To assess the reproducibility and image quality of immediate postgadolinium
      chelate spoiled gradient-echo MRI in demonstrating disease of the abdominal
      aorta. All patients (27 patients: 21 men, 6 women) with substantial disease of
      the abdominal aorta, who underwent abdominal MR examinations at 1.5 T between
      1991 and 1995, were entered in the study. Patients were referred for evaluation
      of suspected aortic disease (14 patients) or other abdominal diseases (13
      patients). Three experienced investigators manually measured luminal and external
      aortic wall diameters and rated image quality, definition of inner and outer
      walls, extent of disease, and presence of other abdominal abnormalities, in an
      independent fashion. A cardiovascular surgeon then rated all studies to determine
      whether clinical management could be based on the MR findings alone. There was 98
      to 99% agreement in measurements of luminal and external wall diameter between
      the three investigators. Overall image quality was rated as good in 77.8 to 88.9%
      of patients. A total of 31 additional nonaortic abdominal abnormalities were
      detected by all observers. The cardiovascular surgeon rated 25 of 27 studies as
      adequate to determine clinical management based on MR findings alone. Immediate
      postgadolinium spoiled gradient-echo MRI is a reproducible technique for the
      demonstration of abdominal aortic disease and possesses good image quality.
      Advantages of this technique include simultaneous evaluation of other nonvascular
      diseases of the abdomen, short examination time, and easy implementation as part
      of routine abdominal MRI scanning protocol.

PMID- 9243384
TI  - Cine MR Fourier velocimetry of blood flow through cardiac valves: comparison with
      Doppler echocardiography.
AB  - Noninvasive measurement of blood flow velocity through the cardiac valves has
      important clinical applications. A wide variety of MR methods are available for
      flow measurement. The aim of this study was to investigate the ability of cine MR
      Fourier velocimetry to measure flow through healthy cardiac valves and to compare
      MR and Doppler peak velocity measurements. Ten healthy volunteers (age mean +/-
      SD, 24 +/- 4 years) without history of valvular disease were studied. Four of the
      subjects were females. In each subject, aortic, pulmonary, mitral, and tricuspid
      valves were evaluated with MR and Doppler imaging. A whole-body mobile MR machine
      was used, operating at .5-T with actively shielded magnetic field gradient coils
      on all three axes capable of 20 mT/m at a slew rate of 60 mT/ m/msec. The heart
      rate during MR and Doppler studies was not significantly different. The mean
      difference between the two studies was 2 beats/min, with a 95% confidence
      interval of -22 beats/min, +25 beats/ min. Peak systolic flow velocity in the
      aortic and pulmonary valves and peak diastolic flow velocity in the mitral and
      tricuspid valves measured with MRI and Doppler echocardiography correlated well.
      The mean difference between the two measurements (MR-Doppler) was 63 mm/sec, with
      a 95% confidence interval of -180 mm/sec, +310 mm/sec. The agreement between two
      observers interpreting the same MR velocity maps was close. The mean difference
      between their two measurements was 23 mm/sec, with a 95% confidence interval of 
      20 mm/sec, +60 mm/sec. There was no significant difference between MR and Doppler
      imaging or between the two MR observers. MR Fourier velocimetry has the necessary
      ease, reliability, and speed to measure blood flow through the cardiac valves,
      although measurement of late diastolic flow in the atrioventricular valves is
      limited. Measurement of peak blood velocity through the cardiac valves by this
      method showed satisfactory agreement with Doppler, but its clinical application
      for assessing diseased cardiac valves must be established.

PMID- 9243386
TI  - MR velocity mapping of tricuspid flow: correction for through-plane motion.
AB  - We evaluated the effect of through-plane motion on tricuspid flow measurements
      performed with MR velocity mapping in nine normal subjects and 15 patients with
      possible right ventricular (RV) disease. Eight parameters of RV diastolic
      function were derived from the tricuspid flow measurements, both before and after
      a correction for through-plane motion. Measurements of E-peak, A-peak, and time
      to-peak filling rate changed significantly after correction for through-plane
      motion (P < .05). Tricuspid flow as a marker of RV diastolic function should be
      corrected for the effect of through-plane motion to improve functional evaluation
      of the RV.

PMID- 9243385
TI  - Effect of artifacts due to flowing blood on the reproducibility of phase-contrast
      measurements of myocardial motion.
AB  - The reproducibility of myocardial motion trajectories calculated from cine phase
      contrast (PC) velocity data is reduced by artifacts due to the inconsistent
      motion of intracardiac blood. Spatial presaturation reduces these artifacts but
      requires a longer sequence TR, with a potentially negative effect on trajectory
      accuracy and reproducibility. We investigated the effect of spatial presaturation
      on trajectory reproducibility. A mid-ventricular transaxial slice was imaged in
      five normal volunteers. The same slice was imaged three times each with sequences
      using spatial presaturation or not. Because the most serious artifacts originate
      in the heart chambers and propagate in the phase-encoded direction, myocardial
      regions that were in line with the heart chambers (in the phase-encode direction)
      had the highest artifact level in the scans without spatial presaturation. The
      reproducibility of trajectories for regions placed in these areas (the anterior
      wall, septum and posterior wall in the transaxial scans with phase encoding in
      the anterior-posterior direction) improved by a factor of two when presaturation
      was used (P < .001). In areas that were not in line with the heart chambers (eg,
      the anterior aspect of the lateral wall in the transaxial scans), the effect of
      presaturation was not significant. These results correlate well with the measured
      reduction in artifact level. The reproducibility of myocardial motion
      trajectories over large areas of the heart is improved to approximately 1 mm when
      presaturation is used. Therefore, use of presaturation is recommended for
      myocardial motion studies using cine PC velocity data.

PMID- 9243387
TI  - Comparison of fat-saturation fast spin echo versus conventional spin-echo MRI in
      the detection of rotator cuff pathology.
AB  - The purpose of this study was to compare the diagnostic performance of fat
      saturation fast-spin-echo (FSE) T2-weighted (T2W) sequences with conventional
      spin-echo (CSE) T2W sequences in the detection of rotator cuff pathology using
      surgery as the reference standard. Oblique coronal dual-echo CSE and FSE T2W
      images with fat saturation from 50 surgically confirmed MR shoulder examinations
      were acquired on a 1.5-T MR scanner. Blinded MR readers retrospectively analyzed
      each imaging sequence separately and ultimately correlated both sequences
      together with findings at surgery. FSE was 100% sensitive and 94% specific in
      detection of full-thickness tears (n = 19) and 73% sensitive and 97% specific in
      the detection of partial-thickness rotator cuff tears (n = 13). There was no
      statistically significant difference in the performance of FSE with fat
      saturation compared with CSE. The two discrepancies between imaging sequences
      related to the extent of partial-thickness tears. Our findings suggest that fat
      saturation FSE imaging can effectively replace CSE imaging in the evaluation of
      rotator cuff pathology.

PMID- 9243389
TI  - Experimental hepatic dysfunction: evaluation by MRI with Gd-EOB-DTPA.
AB  - To investigate the potential of gadolinium (Gd)-ethoxybenzyl (EOB)
      diethylenetriamine-pentaacetic acid (DTPA) for evaluating liver function,
      chemically induced hepatitis animal models were studied. The rats in group 1
      underwent intraperitoneal administration of 2.0 ml/kg and those in group 2
      underwent intraperitoneal administration of .5 ml/kg of 50% (V/V) carbon
      tetrachloride (CCl4) solution. The rats in group 3 served as controls. For rats
      of each group, the signal intensity of the liver was measured on T1-weighted spin
      echo MR images acquired before and until 60 minutes after an intravenous
      injection of Gd-EOB-DTPA. The remaining rats in each group underwent indocyanine
      green test, serologic examination, or measurement of prothrombin time. Liver
      enhancement was compared with results of the other examinations. The degree of
      liver enhancement with Gd-EOB-DTPA was decreased and the washout of contrast was
      prolonged in the CCl4-administered groups. In this animal model, both hepatic
      dysfunction and liver enhancement were dose-dependent. MRI with Gd-EOB-DTPA has
      the potential to evaluate hepatic function.

PMID- 9243388
TI  - Dynamic MRI of a hypovascularized liver tumor model: comparison of a new blood
      pool contrast agent (24-gadolinium-DTPA-cascade-polymer) with gadopentetate
      dimeglumine.
AB  - We evaluated the enhancement properties of a new blood pool contrast agent (24
      gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]-cascade-polymer) in
      comparison with gadopentetate dimeglumine in 24 rabbits with an experimentally
      induced VX-2 liver tumor. Dynamic MRI of the liver was performed before,
      immediately after, and within 15 seconds to 30 minutes after contrast agent
      administration. Relative signal intensities and contrast-to-noise ratios (CNRs)
      of both agents were evaluated. After blood pool agent administration a
      significantly higher CNR between liver and tumor was observed within 2 to 30
      minutes after injection as compared with the CNR after gadopentetate dimeglumine.
      Within 4 to 30 minutes after injection of gadopentetate dimeglumine, the relative
      signal intensities of tumor were significantly higher than after administration
      of the blood pool agent. In conclusion, the new blood pool contrast agent
      demonstrated a significantly better CNR of the experimental hypovascularized
      liver tumor than gadopentetate dimeglumine.

PMID- 9243390
TI  - Papillary projections in ovarian neoplasms: appearance on MRI.
AB  - Papillary projections are distinctive pathologic features of epithelial ovarian
      neoplasms. We sought to determine whether these structures have recognizable
      features on MRI. A search of a database of 125 patients on whom MRI was performed
      with pelvic phased-array coil and abdominal surgical exploration was performed
      for suspected gynecologic disease identified 15 patients who had either MRI
      reports or pathology reports mentioning papillary projections in an adnexal mass.
      The MR images were reviewed to characterize the size, structure, and signal
      intensity of papillary projections. Pathologic correlation was performed on these
      and on four surgical specimens imaged with high resolution technique. Pathologic
      correlation showed that larger papillary projections had a distinctive structure
      of a fibrous stalk supporting clumps of edematous papillae with signal intensity
      similar to that of fluid on T2-weighted images. Smaller papillae showed
      nondescript intracystic projections of intermediate signal intensity on T2
      weighted images. All papillary projections in vivo enhanced after injection of
      gadopentetate dimeglumine. Papillary projections have an appearance on MRI that
      reflects their histologic structure.

PMID- 9243391
TI  - Dynamic MRI of the gallbladder lesions: differentiation of benign from malignant.
AB  - Forty-nine pathologically proven gallbladder lesions were evaluated in 45
      patients using dynamic MRI with a spoiled gradient pulse sequence (SPGR), to
      access the ability of this technique to differentiate benign from malignant
      gallbladder lesions. The studies were reviewed retrospectively. Signal intensity
      of the lesions were measured. Twenty-one malignant and 28 benign lesions were
      classified into three categories: polypoid, diffuse wall thickening, and
      exophytic. Early and delayed enhancement patterns were evaluated. For the
      polypoid masses, malignant lesions (n = 9) demonstrated early and prolonged
      enhancements, whereas benign lesions (n = 14) had early enhancement with
      subsequent washout (P < .05). For diffuse gallbladder wall thickening, malignant
      lesions (n = 6) demonstrated early and prolonged enhancement and benign lesions
      (n = 14) showed relatively slow, prolonged enhancement (P < .05). The exophytic
      masses (n = 6) all were malignant and demonstrated early and prolonged
      enhancement. Dynamic MRI can help differentiate benign from malignant gallbladder
      lesions.

PMID- 9243392
TI  - Pharmacokinetic analysis of Gd-DTPA enhancement in dynamic three-dimensional MRI
      of breast lesions.
AB  - The purpose of this study was to demonstrate that dynamic MRI covering both
      breasts can provide sensitivity for tumor detection as well as specificity and
      sensitivity for differentiation of tumor malignancy. Three-dimensional gradient
      echo scans were used covering both breasts. Before Gd-DTPA bolus injection, two
      scans were obtained with different flip angles, and after injection, a dynamic
      series followed. Thirty-two patients were scanned according to this protocol.
      From these scans. In addition to enhancement, the value of T1 before injection
      was obtained. This was used to estimate the concentration of Gd-DTPA as well as
      the pharmacokinetic parameters governing its time course. Signal enhancement in
      three-dimensional dynamic scanning was shown to be a sensitive basis for
      detection of tumors. In our series, all but two mammographically suspicious
      lesions did enhance, and in three cases, additional enhancing lesions were found,
      two of which were in the contralateral breast. The parameter most suited for
      classification of breast lesions into benign or malignant was shown to be the
      pharmacokinetically defined permeability k31, which, for that test, gave a
      sensitivity of 92% and a specificity of 70%. Our three-dimensional dynamic MRI
      data are sensitive for detection of mammographically occult breast tumors and
      specific for classification of these as benign or malignant.

PMID- 9243393
TI  - Limitations of the keyhole technique for quantitative dynamic contrast-enhanced
      breast MRI.
AB  - The effect of keyhole data acquisition on quantitative analysis of dynamic MRI
      was examined. Experiments were performed retrospectively on raw data obtained
      from clinical dynamic contrast-enhanced breast imaging procedures. The effects of
      keyhole phase-encoding acquisition and type of reconstruction algorithm on the
      accuracy of derived quantitative parameters was assessed. Results indicate that
      the minimum keyhole size used should be restricted by the approximate minimum
      size of the expected lesions. Furthermore, reconstruction algorithms that offer
      improved image resolution do not circumvent this restriction.

PMID- 9243394
TI  - Intracapsular implant rupture: MR findings of incomplete shell collapse.
AB  - The objective of this study was to determine the frequency and significance of
      the MR findings of incomplete shell collapse for detecting implant rupture in a
      series of surgically removed breast prostheses. MR images of 86 breast implants
      in 44 patients were studied retrospectively and correlated with surgical findings
      at explantation. MR findings included (a) complete shell collapse (linguine
      sign), 21 implants; (b) incomplete shell collapse (subcapsular line sign,
      teardrop sign, and keyhole sign), 33 implants; (c) radial folds, 31 implants; and
      (d) normal, 1 implant. The subcapsular line sign was seen in 26 implants, the
      teardrop sign was seen in 27 implants, and the keyhole sign was seen in 23
      implants. At surgery, 48 implants were found to be ruptured and 38 were intact.
      The MR findings of ruptured implants showed signs of incomplete collapse in 52%
      (n = 25), linguine sign in 44% (n = 21), and radial folds in 4% (n = 2). The
      linguine sign perfectly predicted implant rupture, but sensitivity was low.
      Findings of incomplete shell collapse improved sensitivity and negative
      predictive values, and the subcapsular line sign produced a significant
      incremental increase in predictive ability. MRI signs of incomplete shell
      collapse were more common than the linguine sign in ruptured implants and are
      significant contributors to the high sensitivity and negative predictive values
      of MRI for evaluating implant integrity.

PMID- 9243395
TI  - Analysis of magnetization transfer effects on T1-weighted spin-echo scans using a
      simple tissue phantom simulating gadolinium-enhanced brain lesions.
AB  - The purpose of this study was to analyze the effect of several magnetization
      transfer (MT) pulse and T1-weighted spin-echo (SE) sequence parameters on lesion
      to-background contrast, using a simple tissue phantom emulating the T1 relaxation
      and MT properties of gadolinium-enhanced brain lesions. Eggbeaters (Nabisco Inc.,
      East Hanover, NJ) liquid egg product was doped with gadolinium in six
      concentrations from .0 to 1.0 mmol and cooked. The gadolinium-doped egg phantom
      and normal volunteer brains were studied using an SE sequence with TE = 20 msec
      and high power, pulsed, off-resonance MT saturation. The effects of MT pulse
      frequency offset (1,000-6,000 Hz), sequence repetition time (TR = 500-1,000 msec,
      with MT power held constant), and slice-select flip angle (60-120 degrees) on the
      magnetization transfer ratio (MTR) and the simulated lesion-to-background
      contrast were determined at the different "intralesion" gadolinium
      concentrations. The MTR and lesion-to-background contrast of all materials were
      greatest at narrow MT pulse frequency offsets. There was in inverse relationship
      between gadolinium concentration and MTR and a positive correlation between the
      gadolinium concentration and lesion-to-background (L/B) contrast, a weak negative
      correlation between slice-select flip angle and L/B, and a negative correlation
      between TR and L/B. The relaxation properties and MT behavior of the egg phantom
      are close to that expected for enhancing brain lesions, allowing a rigorous
      analysis of several variables affecting lesion-to-background contrast for high MT
      power, T1-weighted SE sequences.

PMID- 9243396
TI  - Progression of a focal ischemic lesion in rat brain during treatment with a novel
      glycine/NMDA antagonist: an in vivo three-dimensional diffusion-weighted MR
      microscopy study.
AB  - Stroke was induced in two groups of anesthetized rats by occlusion of the middle
      cerebral artery (MCA) and ipsilateral common carotid artery. Group 1 (control)
      received vehicle and group 2 received the glycine N-methyl-D-aspartate (NMDA)
      antagonist ZD9379. Stroke volume was assessed by three-dimensional diffusion
      weighted MR microscopy at 2.5 and 6 hours of MCA occlusion. At 2.5 hours, stroke
      volumes were identical in the two groups. At 6 hours, stroke volumes had
      increased by 15% in the control group; in contrast, the treated group showed a
      40% reduced stroke volume. Conclusions from this in vivo study were as follows:
      (a) our technique allows more efficient and accurate measurement of stroke volume
      with an improvement in resolution over a previous method; (b) the ability to
      measure stroke volume at multiple time points shows volume change and assessment
      of time dependency of drug treatment; (c) at 6 hours, the glycine antagonist
      ZD9379 reduced stroke volume by 40%.

PMID- 9243397
TI  - Improved solvent suppression and increased spatial excitation bandwidths for
      three-dimensional PRESS CSI using phase-compensating spectral/spatial spin-echo
      pulses.
AB  - Dual phase-compensating spectral/spatial echo-planar (EP) spin-echo (SE) pulses
      were incorporated into the point resolved spectroscopy (PRESS) excitation
      sequence to improve water and lipid suppression for 1H chemical shift imaging
      (CSI) and to decrease the dependence of the PRESS box location upon chemical
      shift. The asymmetric EPSE pulses (either minimum or maximum phase in the
      chemical shift domain) were substituted for the two PRESS SE pulses to yield zero
      phase spectra. Three different pulses were designed and tested at 1.5 T. Pulse 1,
      targeted for brain CSI (TE > 85 msec), passed choline to lipid resonances,
      suppressed water, and rephased the methyl lactate doublet independently of TE.
      Pulse 2, targeted for general purpose shorter TE PRESS, possessed both high
      chemical shift and spatial domain bandwidths. Pulse 3, designed for prostate CSI,
      passed choline to citrate resonances while suppressing lipids and water. The
      three pulses possessed spatial bandwidths ranging between 3.3 and 5.0 kHz, more
      than three times higher than that offered by one-dimensional SE pulses of
      equivalent maximum B1 amplitude. Phantom and in vivo experimental results
      demonstrated that, for EPSE pulses 1 and 2, suppression factors higher than 10(4)
      were achieved. The increased spatial bandwidths resulted in less contamination by
      signals from outside the designated PRESS excited region and a significant
      improvement in the uniformity of metabolite intensities for voxels located near
      edges of the PRESS box.

PMID- 9243399
TI  - Xenon effects on regional cerebral blood flow assessed by 15O-H2O positron
      emission tomography: implications for hyperpolarized xenon MRI.
AB  - Subjective and physiologic effects of 33% inhaled Xe were measured with 15O-water
      positron emission tomography (PET) in 3 subjects at rest and during visual
      stimulation. The procedure was well tolerated. Robust functional activations of
      the visual cortex were obtained after xenon (Xe) inhalation as well as air
      breathing. However, Xe inhalation was followed by smaller size, but significant
      decreases of regional cerebral blood flow (rCBF) in visual cortex relative to the
      air-breathing baseline, both during visual stimulation and at rest. No such
      decreases were found in other sensory or motor regions.

PMID- 9243398
TI  - Massive edema of the ovary: high resolution MR findings using a phased-array
      pelvic coil.
AB  - We report a rare premenarchal case of massive ovarian edema in which high
      resolution MRI findings more accurately reflected characteristic pathologic
      changes of this condition compared with CT and ultrasound. A potential role of MR
      in preoperative diagnosis of massive ovarian edema is suggested.

PMID- 9243400
TI  - Use of an intravascular T1 contrast agent to improve MR cine myocardial-blood
      pool definition in man.
AB  - The feasibility of improving myocardial/blood pool contrast in MR cine images
      through use of an intravascular contrast agent (Ferumoxtran, Advanced Magnetics,
      Inc., Cambridge, MA) was tested in four subjects. The contrast-to-noise ratio
      (CNR) demonstrated a trend toward improvement in the short axis and improved
      significantly in the long axis cine by an average of 128% (P < .05). Image
      intensity gradients at the myocardial/blood pool interface increased
      significantly in both the short and long axis (P < .01). It is expected that
      larger image intensity gradients at the endocardial border should improve the
      capabilities of automated segmentation algorithms, reducing the uncertainty and
      need for manual editing.

PMID- 9243401
TI  - Paradoxic uptake of Gd-EOB-DTPA by hepatocellular carcinoma in mice: quantitative
      image analysis.
AB  - To determine whether paradoxic uptake of gadolinium-ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) occurs only with highly
      differentiated hepatocellular carcinomas, quantitative image analysis was
      performed in 37 mice with 133 hepatocellular carcinomas. The results of lesion/
      liver signal intensity measurement and relative enhancement calculation indicate
      that paradoxic positive enhancement occurs independently of cellular
      differentiation.

PMID- 9243402
TI  - MRI of cervical fixation devices: sensation of heating caused by vibration of
      metallic components.

PMID- 9243403
TI  - Postural imbalance and vibratory sensitivity in patients with idiopathic
      scoliosis: implications for treatment.
AB  - Sporadic research reports of decreased proprioception and balance problems have
      been reported in subjects with idiopathic scoliosis, yet these sensory motor
      deficits have not been addressed in conservative clinical management programs.
      The purpose of this study was to compare both balance reactions and vibratory
      sensitivity (as an estimate of proprioception) in patients with idiopathic
      scoliosis (N = 24) and age-matched controls (N = 24). Balance was measured by the
      ability to pass a series of simple static and complex sensory-challenged balance
      tasks. Vibratory thresholds were measured with the Bio-Thesiometer at the
      cervical spine, wrist, and foot. Compared with age-matched controls, regardless
      of curve severity or spinal fusion, the subjects with idiopathic scoliosis had
      similar simple static balance responses when the somatosensory system was stable
      (with or without vision or head turning), but they were significantly more likely
      to fail the complex, sensory-challenged balance tasks when the somatosensory
      system was challenged by an unstable position of the feet, particularly when the
      eyes were closed. The vibratory thresholds were similar in subjects with
      scoliosis and their age-matched controls, but individuals with moderate to severe
      scoliosis (> 25 degrees) had significantly higher vibratory thresholds than those
      with mild curves. These findings suggest there may be problems with postural
      righting in patients with idiopathic scoliosis, particularly when the balance
      task challenges the vestibular pathways. Although vibration sensitivity did not
      distinguish normal healthy individuals from individuals with idiopathic
      scoliosis, those with more severe scoliotic curves appear to have a high
      threshold to vibration. These balance and vibratory differences could either be
      interpreted as etiologic risk factors or as consequences of spinal asymmetry. In
      either case, given that curves can continue to progress even into the adult
      years, improving the ability to right the body with gravity could help maintain
      the balance of the spine despite structural asymmetry.

PMID- 9243404
TI  - Economy of mobility in older adults.
AB  - A decline in economy of mobility indicates that more physical work is required
      for a task (ie., walking) and may suggest an abnormal gait pattern. A normal gait
      pattern is essential for maintaining independence in older adults. The purpose of
      this study was to compare economy of mobility between sedentary older men and
      women. The subjects were 47 men (mean +/- SD; age = 71 +/- 4 years, weight = 83
      +/- 8 kg, height = 175 +/- 7 cm) and 51 women (70 +/- 3 years, 65 +/- 8 kg, 161
      +/- 5 cm). Men were significantly (p < 0.05) older, heavier, and taller than
      women. Maximal oxygen uptake (VO2max) was collected while subjects walked on a
      treadmill until volitional exhaustion. On a separate day, a submaximal test was
      performed at one speed requiring approximately 60% of VO2max on a level treadmill
      for 5 minutes. Men had significantly greater absolute and relative VO2max than
      women. Men walked at a significantly faster speed (92 +/- 8 vs. 86 +/- 7 m/min)
      than women during the submaximal test. Economy of mobility was the same for older
      men and women (0.17 +/- 0.02 ml/kg/m) with differences in walking speed
      controlled. The results indicate that there is not a gender-specific decrement in
      economy of mobility with aging.

PMID- 9243406
TI  - Invertor vs. evertor peak torque and power deficiencies associated with lateral
      ankle ligament injury.
AB  - Strengthening of the evertor muscles is widely advocated as a key component of
      lateral ankle sprain rehabilitation, but our clinical observation of impaired
      invertor muscle performance among many patients suggested the need for this study
      of isokinetic performance deficiencies. Subjects were 30 physically active
      adolescents, ages 14-19 years, who had recently sustained a lateral ankle sprain
      or who had symptoms of chronic lateral ankle instability. Eversion/inversion
      testing was performed on a Biodex isokinetic dynamometer at speeds of 30 and 120
      degrees/sec. Analysis of variance results demonstrated significantly greater (p <
      .05) invertor deficits than evertor deficits for both peak torque and average
      power at both tests speeds. The findings of this study suggest that a lateral
      ankle ligament injury may be associated with an invertor muscle performance
      deficiency, and that restoration of a normal evertor/invertor strength
      relationship may be accomplished through performance of an isotonic ankle
      strengthening program.

PMID- 9243405
TI  - The effect of sudden inversion stress on EMG activity of the peroneal and
      tibialis anterior muscles in the chronically unstable ankle.
AB  - Residual symptoms resulting from recurrent episodes of inversion-type ankle
      sprains may be attributed to a decreased neuromuscular response of the peroneal
      or tibialis anterior muscles, thereby increasing the probability for reinjury.
      The purpose of this study was to examine the electromyographic (EMG) response
      time of the peroneal and tibialis anterior muscles in response to sudden plantar
      flexion/inversion stress in the chronically functional unstable and normal ankle.
      Subjects for this study consisted of 13 athletically active individuals (five
      males and eight females, mean age = 19.2 +/- 1.51 years) with a previous history
      of a unilateral inversion-type ankle sprain. A specially designed platform that
      allows each foot to drop into plantar flexion/inversion from a standing neutral
      position was used. Reaction time in milliseconds for the peroneal and tibialis
      anterior muscles to sudden plantar flexion/inversion was measured via surface
      EMG. A paired t test was performed with the Bonferroni-Dunn correction factor to
      determine differences between the peroneal and tibialis anterior as well as
      between the chronically unstable and contralateral normal ankle. The results
      indicated no significant differences between the stable and unstable ankles for
      the peroneal or the tibialis anterior muscles. The results also indicated no
      significant differences existed between the tibialis anterior and peroneal
      muscles in either the stable or unstable ankles. The findings from the present
      study suggest that self-reported functional ankle instability may not result in a
      diminished reflex response time of the peroneal and tibialis anterior muscles to
      sudden plantar flexion/inversion stress.

PMID- 9243407
TI  - Profile of dance injuries in a Broadway show: a discussion of issues in dance
      medicine epidemiology.
AB  - A description of dance injuries in a Broadway show using ballet technique is
      reported for the first time. Presentation of this material is used as a vehicle
      to discuss issues in dance epidemiology and etiology. As interest and research in
      dance medicine increases, standardization of reporting methods and definitions
      becomes critical in discussions of epidemiology and etiology. Borrowing from
      sports medicine classifications, which define sports injury as "time lost from
      play," we suggest dance injury be defined as "time lost from performing". The
      overall injury rate was 40.0%, which was low compared with those of classical
      ballet companies. The majority of injuries involved the foot and ankle, similar
      to previous reports of classical ballet companies. Reasons for the low injury
      rates and types of injuries are discussed. The information necessary to
      facilitate comparison of data with other studies is outlined. We hope this
      article will contribute to further discussion regarding adoption of universal
      language and details necessary for reporting injury. Additional areas of research
      are suggested.

PMID- 9243408
TI  - The controversy of cranial bone motion.
AB  - Cranial bone motion continues to stimulate controversy. This controversy affects
      the general acceptance of some intervention methods used by physical therapists,
      namely, cranial osteopathic and craniosacral therapy techniques. Core to these
      intervention techniques is the belief that cranial bone mobility provides a
      compliant system where somatic dysfunction can occur and therapeutic techniques
      can be applied. Diversity of opinion over the truth of this concept characterizes
      differing viewpoints on the anatomy and physiology of the cranial complex.
      Literature on cranial bone motion was reviewed for the purpose of better
      understanding this topic. Published research overall was scant and inconclusive.
      Animal and human studies demonstrate a potential for small magnitude motion.
      Physical therapists should carefully scrutinize the literature presented as
      evidence for cranial bone motion. Further research is needed to resolve this
      controversy. Outcomes research, however, is needed to validate cranial bone
      mobilization as an effective treatment.

PMID- 9243409
TI  - Survival in the new order of healthcare.

PMID- 9243410
TI  - Scientific application of sports medicine principles for acute low back problems.

PMID- 9243411
TI  - Reflex response times of vastus medialis oblique and vastus lateralis in normal
      subjects and in subjects with patellofemoral pain.

PMID- 9243412
TI  - Getting medications despite HMO cost cutting.

PMID- 9243413
TI  - Supporting people with disabilities.

PMID- 9243414
TI  - The medical patient in psychiatric practice.

PMID- 9243415
TI  - Trauma history may shed light on elusive alcoholics.

PMID- 9243416
TI  - Substance abuse, treatment, and the courts. Alcohol and drug abuse contributing
      factor in 80% of U.S. crimes.

PMID- 9243417
TI  - Can infection result in OCD?

PMID- 9243418
TI  - Heat stroke. Keeping your clients cool in the summer.
AB  - Persons with persistent, disabling mental illness have an increased risk of heat
      related illness. Mental health care providers must be aware of this risk, and
      should be educated regarding detection and prevention. A high level of awareness
      and monitoring for symptoms of heat-related illness is indicated during the
      initial days of a heat wave. Health professionals must ensure that consumers know
      about the risk of heat stroke and have a plan in place to deal with hot weather.
      Plans must be practical, affordable, and take into account the preferences,
      habits, and psychiatric symptoms of the individual who will carry them out.
      Thoughtful planning and education can help reduce the risk of heat-related
      illness in this vulnerable group.

PMID- 9243419
TI  - Dually diagnosed inpatients' satisfaction with addiction groups.
AB  - 1. This clinical report presents evaluations from 50 hospitalized dually
      diagnosed patients of the Addiction Education Group, a part of the inpatient dual
      diagnosis treatment program. 2. Patient satisfaction with the group was evaluated
      using the Client Satisfaction Questionnaire, an eight-item tool that measures
      reported satisfaction with services. 3. Generally, the patients were able to
      focus on issues of recovery as a group, provide and receive feedback from each
      other, and perceive the experience as beneficial.

PMID- 9243420
TI  - Naltrexone: a controversial therapy for alcohol dependence.
AB  - 1. Naltrexone HCL (ReVia) may be an effective adjunct in the treatment of alcohol
      dependence in motivated individuals. 2. Naltrexone therapy is controversial
      because its use conflicts with the view of abstinence held by Alcoholics
      Anonymous and most medical treatment programs. 3. Knowledge of the controversy
      can help nurses advocate for their patients, and may help nurses acknowledge the
      need to define their care according to a nursing paradigm.

PMID- 9243421
TI  - Screening cognitive impairment in alcohol abusers.
AB  - 1. Studies have reported various neuropsychological abnormalities in people with
      excessive drinking patterns and associated problems with the assessment and
      treatment of this group. 2. The aim of this study was to assess the potential of
      a screening instrument to help detect the presence of cognitive impairment in
      excessive alcohol users undergoing detoxification. 3. The Memory Screening Test
      has potential as a screening instrument to assess clients' cognitive ability to
      benefit from psychoeducational material.

PMID- 9243422
TI  - Impact of a body-mind treatment component on alcoholic inpatients.
AB  - 1. A group of alcoholic patients who were treated with a physical fitness program
      as an adjunct to the usual program showed significantly less craving for alcohol
      than members in the standard treatment group. 2. The group treated with physical
      fitness as well as therapy saw themselves as having more internal locus of
      control and being less controlled by powerful others. 3. Nurses are the hospital
      professionals most likely to be involved with important roles in exercise
      programs with alcoholic patients.

PMID- 9243423
TI  - Guilt and shame in recovering addicts. A personal account.
AB  - 1. Guilt and shame, although distinct and difficult emotions, share equal
      importance in recovery from addiction. 2. Twelve-step programs, as well as other
      treatment options, are available to help the recovering addict deal with feelings
      of guilt and shame. 3. By learning to place shame in perspective and to use guilt
      as a catalyst for improvement, recovering addicts can begin to heal.

PMID- 9243424
TI  - A new national classification of health services based on clinical effectiveness.

PMID- 9243425
TI  - Drinking water and microbiological pathogens--issues and challenges for the year
      2000.

PMID- 9243426
TI  - Short postnatal hospital stay: implications for women and service providers.
AB  - BACKGROUND: In a bid to increase consumer satisfaction, recent government reports
      have encouraged maternity services providers to offer women more choice about
      their care. At the same time, there has been considerable pressure on hospital
      managers and clinicians to drive down health service costs. Women need
      information about the likely effects of different service patterns on their
      wellbeing, and service providers about the implications of allowing women choice.
      METHODS: This paper reports on a descriptive study in six districts in the
      Yorkshire Region and focuses on the implications of variation in length of stay.
      The aim of the study was to describe variation in the care process and to explore
      associations between care process variables, consumer satisfaction and maternal
      psychological wellbeing. One hundred and twenty randomly selected women in each
      district delivering in a specified four-week period were asked to complete postal
      survey questionnaires in the postnatal period. RESULTS: There were significant
      differences between districts in terms of the length of postnatal hospital stay
      for women experiencing normal deliveries. Those women who thought that their
      postnatal length of stay was too short had significantly higher depression
      scores. CONCLUSIONS: Variation in length of postnatal hospital stay may have
      implications for consumer satisfaction, maternal psychological outcomes and
      resource use.

PMID- 9243427
TI  - A medical school in Zambia.

PMID- 9243428
TI  - The use of mapping in public health and planning health services.
AB  - The availability of relatively inexpensive, user-friendly geographical
      information systems, with a steadily extending range of analytic and other
      facilities, provides a powerful tool for the analysis and display of the
      increasing number of health-related data sets, and for their greater
      accessibility. Relationships between several sets of variables can become
      immediately apparent from a map in a way that is much more difficult to
      comprehend from a table or description. It is also easy to define ad hoc areas,
      such as the area adjacent to a possible toxic point source or to a main road, in
      terms of unit postcodes and Census output areas, to determine standardized rates
      for mortality and hospital admissions. Apart from the geographical information
      system itself, the basic requirements are access to relevant data sets including
      Census data, and to the central postcode directory, which provides grid
      references for unit postcodes and permits matching of postcoded health events to
      Census output areas.

PMID- 9243429
TI  - Pathways to orthodontic care.
AB  - BACKGROUND: The research described in this paper arose out of the need to address
      the growing waiting list for orthodontic treatment in Northamptonshire. Although
      the prevalence of dento-facial anomalies is the same across time, sex, race and
      socio-economic class, studies in the United States and this country suggest that
      certain groups are over-represented among patients who receive orthodontic
      treatment. The introduction of valid and reliable indices of therapeutic need
      such as the index of Orthodontic Treatment Need (IOTN) will allow improved
      focusing of services. The aim of the study was to determine the variables
      affecting access to orthodontic care, and the extent to which services were
      delivered according to objective measures of need. METHODS: Analyses were
      undertaken for speed, appropriateness, timing of referral, duration and
      complexity of the pathway for new referrals to specialist orthodontic care.
      possible explanations for the length of pathway were examined, including socio
      demographic factors, location of residence and the IOTN. RESULTS: A total of 405
      patients were approached, of whom 400 (99 per cent) agreed to participate. There
      was an over-representation among socio-economic groups I and V among patients
      referred to orthodontic treatment. By contrast, those of male sex and from socio
      economic class IV were under-represented. This appeared to be the case
      irrespective of treatment setting. There was also a wide range of waiting times
      to treatment and complexity of pathway. Over a quarter of the sample had been
      inappropriately referred, and objective need as measured by the IOTN was not a
      determinant in the speed of access to specialist treatment. Adult patients waited
      longer for treatment. CONCLUSIONS: These results suggest that the delivery of
      care is neither based on objective need nor equitably distributed. More
      appropriate directing of resources is required, using the IOTN and agreed
      protocols, so that referrals are made to the most suitable provider.

PMID- 9243430
TI  - Social class, spoken language and pattern of care as determinants of continuity
      of carer in maternity services in east London.
AB  - BACKGROUND: The Government's policy of Changing childbirth gives priority to user
      oriented outcomes, such as continuity of carer. It has been assumed that the
      organization (or pattern) of maternity care is the main determinant of
      continuity, with relatively little attention paid to sociodemographic factors.
      The aim of this study was to assess the relative contribution of social class,
      spoken language and pattern of care in determining continuity of carer. METHOD:
      Postal questionnaires were sent 14 days after delivery to East London and the
      City Health Authority residents delivering within a three-week period in May
      1994. Bilingual interviews were carried out for non-English-speaking women.
      Pattern of care was assigned by the midwife as either hospital or community
      (including team based care, 'domino' and home births). The main outcome measure
      was self-reported continuity of carer in antenatal, delivery and postnatal care.
      RESULTS: The response rate was 69 per cent (370/533). The community pattern of
      care affected only antenatal continuity (62 per cent community vs 50 per cent
      hospital, p < 0.05). Women whose main spoken language was English or whose social
      class was I-IIIn reported higher levels of continuity at each phase of care,
      although this effect was largely confined to the community pattern of care. The
      odds ratios (95 per cent confidence intervals) for the effect of social class (I
      IIIn vs other) on antenatal, labour and postnatal continuity within the community
      pattern of care were 3.64 (1.09-12.18), 3.08 (1.09-8.74) and 4.93 (1.48-16.46),
      respectively. CONCLUSION: Spoken English and high social class were associated
      with continuity of carer, although this effect was mainly confined to women with
      a community pattern of care. Achievement of national targets for continuity of
      carer may not be possible in east London without explicit consideration of
      sociodemographic factors.

PMID- 9243431
TI  - Community immunization programme in response to an outbreak of invasive Neisseria
      meningitidis serogroup C infection in the Trent region of England 1995-1996.
AB  - Between 8 December 1995 and 16 January 1996 seven laboratory confirmed cases of
      septicaemia owing to infection with Neisseria meningitidis serogroup C strains
      and one highly probable case of meningococcal septicaemia occurred in three
      electoral wards in south Rotherham and the Retford area of north Nottinghamshire.
      All cases occurred among children aged 1-17 years. One patient died. The public
      health response to this outbreak was the largest community prophylactic
      antibiotic and immunization programme against meningococcal infection, to date,
      in the United Kingdom. The target group for each Health Authority was 8900 for
      Rotherham Health Authorities and 8000 for North Nottinghamshire Health. Local
      logistical factors led to differences in the implementation of the programme by
      each Health Authority. At the completion of each programme, 8320 doses of vaccine
      had been administered (92.5 per cent coverage) during the Rotherham Health
      Authorities programme and 7660 (95.7 per cent coverage) during the North
      Nottinghamshire Health programme. The additional financial cost of the exercise
      amounted to approximately Pounds 125000 for each Health Authority. This paper
      describes the evolution of the outbreak, the decision-making process resulting in
      the immunization programme in each Health Authority, the implementation of each
      programme, problems identified and lessons learned.

PMID- 9243432
TI  - New players for a new era: responding to the global public health challenges.

PMID- 9243433
TI  - A shorter form health survey: can the SF-12 replicate results from the SF-36 in
      longitudinal studies?
AB  - BACKGROUND: The SF-36 is a generic health status measure which has gained
      popularity as a measure of outcome in a wide variety of patient groups and social
      surveys. However, there is a need for even shorter measures, which reduce
      respondent burden. The developers of the SF-36 have consequently suggested that a
      12-item sub-set of the items may accurately reproduce the two summary component
      scores which can be derived from the SF-36 [the Physical Component Summary Score
      (PCS) and Mental Health Component Summary Score (MCS)]. In this paper, we adopt
      scoring algorithms for the UK SF-36 and SF-12 summary scores to evaluate the
      picture of change gained in various treatment groups. METHODS: The SF-36 was
      administered in three treatment groups (ACE inhibitors for congestive heart
      failure, continuous positive airways therapy for sleep apnoea, and open vs
      laparoscopic surgery for inguinal hernia). RESULTS: PCS and MCS scores calculated
      from the SF-36 or a sub-set of 12 items (the 'SF-12') were virtually identical,
      and indicated the same magnitude of ill-health and degree of change over time.
      CONCLUSION: The results suggest that where two summary scores of health status
      are adequate than the SF-12 may be the instrument of choice.

PMID- 9243434
TI  - The pregnant smoker: a preliminary investigation of the social and psychological
      influences.
AB  - BACKGROUND: Smoking during pregnancy is an important challenge to public health.
      An understanding of the psychological and sociological bases of maternal smoking
      is essential to the development of effective smoking cessation interventions. The
      aim of this study was to explore the psychosocial factors that underpin maternal
      smoking. METHODS: Semi-structured interviews were conducted with 200 antenatal
      attenders at Leicester Royal Infirmary, NHS Trust, UK. RESULTS: Twenty-nine per
      cent were smokers, 22 per cent ex-smokers and 49 per cent were never smokers.
      Around half of the ex-smokers (49 per cent) had reportedly given up smoking
      during their current pregnancy. Around a third (29.5 per cent) of the ex-smokers
      had experienced previous problems associated with maternal smoking, including
      spontaneous abortion, cot death and premature birth. Of the current smokers, 69
      per cent claimed that they would like to give up smoking; indeed, 59 per cent had
      tried to stop smoking. Emotional factors were important in maintaining smoking
      for two-thirds of the smokers. Significantly more of the smokers (75 per cent)
      had partners who smoked compared with the never-smoking women (30 per cent; p <
      0.001). There was no difference in the level of knowledge about the dangers of
      maternal smoking between smokers, ex-smokers and never smokers. CONCLUSIONS:
      Pregnant smokers are as aware of the health risks as non-smokers. Effective
      intervention strategies need to focus not only on the pregnant woman's smoking
      status but also offer help to partners, close family members and friends.
      Interventions need to address the social and psychological factors that maintain
      maternal smoking.

PMID- 9243435
TI  - Outcome measures in palliative care for advanced cancer patients: a review.
AB  - Information generated using outcome measures to measure the effectiveness of
      palliative care interventions is potentially invaluable. Depending on the
      measurement tool employed the results can be used to monitor clinical care, carry
      out comparative research, provide audit data or inform purchasing decisions.
      However, the data collected can only ever be as good as the method used to obtain
      them. This review aimed to systematically identify and examine outcome measures
      that have been used, or proposed for use in the clinical audit of palliative care
      of patients with advanced cancer. Database searches were performed using MEDLINE
      (1991-1995), CANCERLIT (1991-1995), Healthplan (1985-1995), and 'Oncolink' on the
      internet. Further measures were located with the assistance of other
      professionals working in palliative care. The criteria for the inclusion and
      assessment of measures were a measure assessing more than one domain and a target
      population of advanced disease or palliative care Forty-one measures were
      identified, 12 of which satisfied the inclusion criteria. These contained between
      five and 56 items and covered aspects of physical, psychological and spiritual
      domains. Each measure meets some but not all of the objectives of measurement in
      palliative care, and fulfils some but not all of our criteria for validity,
      reliability, responsiveness and appropriateness.

PMID- 9243436
TI  - Hepatitis B, 1997 and the Chinese community--an appraisal of their relationships.
AB  - In 1997, Hong Kong's sovereignty will go back to China. The United Kingdom has
      granted 50,000 families the right of abode to settle here. It is estimated that
      these 50,000 families will consist of approximately 225,000 people in all.
      Hepatitis B virus infection is extremely common in Hong Kong-50 per cent of the
      local population have been infected by the virus. Should the Department of Health
      consider implementing and introducing a screening and immunization programme?
      What is the current level of understanding about the virus among the Chinese
      community and health care professionals in the United Kingdom? Findings from a
      health promotion project have revealed that there is a gap in health care
      professionals' and patients' understanding of the issue. There is a need to raise
      awareness, to provide more information for health care professionals and
      patients, and to give serious consideration to a screening and vaccination
      programme.

PMID- 9243437
TI  - Non-response bias in a lifestyle survey.
AB  - BACKGROUND: Monitoring health targets is often undertaken using questionnaire
      surveys of lifestyle risk factors. Non-response bias is recognized but rarely
      quantified. METHODS: Following a questionnaire survey on a random sample of 6009
      residents of Somerset with a response rate of 57.6 per cent, a telephone survey
      was undertaken on a random sample of 400 non-responders. A small number of the
      more important questions from the questionnaire were put to the non-responders
      over the phone. RESULTS: Fifty-nine per cent of the sample were contacted and
      agreed to participate. Statistically significant differences between responders
      and non-responders to the original questionnaire were detected for current
      smoking, hazardous alcohol consumption and lack of moderate or vigorous activity.
      CONCLUSIONS: Lifestyle questionnaire surveys need to include an assessment of the
      non-response bias.

PMID- 9243438
TI  - Prevention of post splenectomy sepsis: a population based approach.
AB  - BACKGROUND: The aim of the study was to prevent the occurrence of serious,
      overwhelming infection following splenectomy, by a district based initiative.
      Subjects were residents of Plymouth and Torbay District Health Authority (DHA)
      who had undergone splenectomy in the past and general practitioners (GPs) within
      the District. METHODS: District guidelines on the prevention of post splenectomy
      sepsis were developed and disseminated among local GPs and hospital doctors.
      Patients who had undergone operative splenectomy were actively traced through GP
      and hospital information systems so that they could be offered sepsis preventive
      measures in accordance with the guidelines. Data capture-recapture was used as an
      ascertainment adjustment method to estimate the district prevalence of alive
      patients who have had an operative splenectomy. A postal questionnaire of
      district GPs was undertaken after one year to determine their awareness and use
      of the guidelines. RESULTS: Eight-eight alive patients who had undergone
      splenectomy were not previously identified be their GP as being asplenic. They
      were traced so that they could be offered sepsis preventive measures in line with
      the local guidelines. The estimated district prevalence of individuals who had
      had an operative splenectomy after ascertainment adjustment using data capture
      recapture is p = 9.75 per 10,000 population [95 per cent confidence interval (CI)
      (7.87, 11.64) per 10,000]. Out of 367 district GPs, 201 used the local guidelines
      after one year. CONCLUSIONS: Effective prevention of overwhelming infection
      following splenectomy requires an active population based approach.

PMID- 9243439
TI  - Appendicectomy in Scotland: a 20-year epidemiological comparison.
AB  - BACKGROUND: The objective of the research was to study the pattern of
      appendicectomies in Scotland over the last 20 years. METHOD: Routine National
      Health Service data on patients discharged after appendicectomy in Scotland
      during 1973-1993 were analysed. RESULTS: For all ages, the appendicectomy rate
      has fallen steadily from 1.97 per 1000 (10,325 operations) in 1973 to 0.96 per
      1000 (4906 operations) in 1993. The proportion of emergency operations increased
      from 76 to 80 per cent. The median age at operation rose from 18 to 22 years. The
      proportion of male patients remained higher for emergency operations, whereas the
      proportion of females, and age at operation, were both higher for non-emergency
      appendicectomies. In the period 1992-1995, appendicectomy rates were higher for
      patients with postcodes in areas of greater deprivation, particularly for
      children aged 0-14 years. Variation in childhood appendicectomy rates across
      Scotland has declined: apart from Ayrshire and Arran, which had a lower than
      expected rate, no Health Board had a rate significantly different from the rate
      in the rest of Scotland in 1993. The case fatality rate fell from 7.0 per 1000 to
      1.6 per 1000 (with all the latter deaths in elderly patients). CONCLUSION: Over
      the last 20 years, appendicectomy rates have declined in Scotland and there is
      now greater uniformity of childhood appendicectomy rates across Scotland.

PMID- 9243440
TI  - A randomized trial of the impact of telephone and recorded delivery reminders on
      the response rate to research questionnaires.
AB  - BACKGROUND: A range of factors have been shown to affect the response rate to
      mailed questionnaires, but particular strategies to improve patients' response in
      trials conducted in general practice require further study. METHODS: Non
      responders in a larger trial were randomized to receive a telephone or recorded
      delivery reminder on the third contact. The cost of administration of each method
      was estimated. RESULTS: Significantly more patients returned completed
      questionnaires when sent questionnaires by recorded delivery, although the cost
      per patient contacted was nearly three times more than for contact by telephone.
      CONCLUSION: Our study indicates that sending reminders by recorded delivery,
      although more expensive, is more effective than telephone reminders for
      recruiting patients to a study in general practice using research questionnaires.

PMID- 9243441
TI  - Screening for Chlamydia in general practice: a literature review and summary of
      the evidence.
AB  - Genital Chlamydia trachomatis infection is the commonest curable sexually
      transmitted disease (STD) in England and Wales and is one of the chief causes of
      pelvic inflammatory disease (PID) in women. Infection in women is complicated by
      the fact that the majority of women with this infection are asymptomatic. It is
      feasible for general practitioners (GPs) to test for this infection, and there
      has been debate as to which is the most appropriate screening strategy. In the
      absence of any national UK guidelines, the purpose of this systematic literature
      review is to appraise critically and summarize the evidence for screening for
      genital chlamydia infection in sexually active women attending UK general
      practice. The four areas to be reviewed are: prevalence of genital chlamydia
      infection in women attending UK general practice; evidence for routine screening
      of women attending general practice; evidence for selective screening of women
      attending general practice; evidence for screening women requesting termination
      of pregnancy (TOP) or intrauterine device (IUD) insertion. This review should
      allow GPs and public health practitioners to become aware of the quality of
      evidence underlying various screening strategies and inform any local guideline
      development.

PMID- 9243443
TI  - A new kind of public health doctor.

PMID- 9243442
TI  - Quarterly communicable disease review. October to December 1996. From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 9243444
TI  - The pursuit of research publications.

PMID- 9243445
TI  - Creative misreading: why we talk past each other.
AB  - A close look at Gedo's recent paper on working through reveals a number of
      devices used in the development of competing psychoanalytic theories, devices
      which result in analysts talking past each other. Starting with the notion that
      all theorists "misread" their predecessors, the author examines how different
      views of the past create confusion in the dialogue between Gedo and his
      commentators. He then takes up the issue of how data emerging from the
      neurosciences can be used to support many different psychoanalytic theories and
      suggests that there will always be a "metaphorical leap" from one frame of
      reference to the other. Finally, he examines how the drawing of sharp dichotomies
      both within a theory and between one theory and another misrepresents analytic
      work and exaggerates differences between one point of view and another. Thus,
      various devices that are used to buttress one version of analytic theory make it
      more difficult to develop a more integrated theory and to correlate
      psychoanalytic data with those emerging from the neurosciences.

PMID- 9243446
TI  - Clinical and developmental dimensions of hate.
AB  - Bridging concepts of aggression, affect, and attitude, hate emerges during the
      process of separation-individuation concurrent with ego development and
      persisting intrapsychic conflict and fantasy. Rage precedes hate developmentally,
      though later the two are amalgamated both developmentally and clinically. Hate is
      the negative pole of ambivalence and is a component of all self- and object
      representations and object relationships. When excessive and unmodulated, hate
      interferes with object relations and personality development. Paradoxically, hate
      may also subserve adaptation and personality organization. Transference hate is
      often a greater problem for the psychoanalyst or psychotherapist than is
      transference love. Transference hate threatens the analyst's narcissism and
      neutrality and tests the analyst's tolerance and patience. The patient's intense
      hate is often experienced as a direct assault on the analytic relationship and
      the analytic process. Countertransference hate and the need to defend against it
      are of great clinical importance. Because it runs counter to analytic ideals and
      values, the analyst's hatred of the patient may be denied, minimized,
      rationalized, enacted, or vicariously gratified and may occasion great resistance
      to analytic self-scrutiny. Countertransference hate is often an unrecognized
      determinant in cases of analytic and therapeutic impasse. A classic contribution
      by D.W. Winnicott to the recognition and elucidation of countertransference hate
      is reevaluated.

PMID- 9243447
TI  - Safety, danger, and the analyst's authority.
AB  - The concepts of safety and danger as they pertain to the psychoanalytic situation
      are examined, with a special interest in casting aside familiar unquestioned
      presumptions about the therapeutic effects of the analyst and the setting as safe
      and therefore facilitating of self-disclosure, insight, and change. The merit of
      viewing the situation as in itself neither safe nor dangerous is argued, and
      problems are noted in the uncritical acceptance of the illusion of safety and
      attempts to use it for therapeutic purposes. Such an illusion denies the
      psychological and biological vulnerability of all human beings, especially in
      relation to aggression. In the clinical setting, working from an unexamined
      presumption of safety interferes with full transference expression and the
      analysis of aggression, often in the service of sparing the analyst from fully
      experiencing the analysand's adult aggressive potential. Contemporary interest in
      the analyst's authority, particularly efforts to undo it, can profitably be
      viewed as helping to maintain an illusion of safety during treatment in order to
      avoid the real dangers that are experienced as present and that are therefore
      available for exploration and mastery.

PMID- 9243448
TI  - The analyst's reality.
AB  - Attention is called to ways in which the analyst's subjective experience and
      judgment of reality, aspects of his or her psychic reality, not only are
      necessary to the effective conduct of any psychoanalysis but play a positive and
      useful role. The theoretical framework of ego psychology risks overemphasizing
      the primacy of the analyst's reality, while self psychology risks discarding it
      in favor of the patient's psychic reality. Each view has its dangers, and an
      integration of both should be sought without losing the advantages of either.
      Although the analyst's view of reality may in some instances be relatively
      privileged, most often it is valuable as a heuristic device focusing the
      analyst's attention when a discrepancy appears between the patient's version of
      reality and that of the analyst. When used in such a manner, it enhances rather
      than detracts from the analytic, empathic investigation of the patient's reality.

PMID- 9243449
TI  - Understanding the patient's use of the method of free association: an ego
      psychological approach.
AB  - While most of our methods of listening have been geared toward unearthing
      unconscious fantasies, those directed toward the ego's all-inclusive role in
      effecting the associative process have lagged far behind. It is the thesis of
      this paper that listening from the perspective of the ego allows the analyst to
      work more closely with what the patient is ready to understand. Clinical
      technique, using an ego psychological view, is elaborated, demonstrated, and
      compared to technique dependent on the reading of signs and symbols of the
      unconscious.

PMID- 9243451
TI  - The logic of controversy: Susan Isaacs and Anna Freud on F(PH)antasy.
AB  - Controversy leaves its mark on the subsequent development of psychoanalytic
      concepts in the form of ambiguous language and faulty reasoning. Examination of
      the form of an historical controversy suggests that enduring inconsistencies and
      a less than comprehensive appreciation of the strengths and weaknesses of the
      competing theories resulted from the emotional and political climate. The authors
      recommend that disputes over new theoretical proposals begin with (1) an
      identification of the clinical problems that are said to require the innovation
      and (2) an assessment of whether the identified problems actually require
      theoretical revision. The new model should then be examined (3) as to whether it
      is self-sufficient or depends on unrecognized aspects of the previous theory. In
      the latter case, (4) it is important, in order to avoid the emergence of a self
      contradictory theoretical hybrid, to ascertain whether the new formulation
      contradicts the previous one on which it silently depends.

PMID- 9243452
TI  - Three forms of meaning and their psychoanalytic significance.
AB  - The existence of three distinct forms of meaning--unearthed, reshaped, and
      improvised--is claimed to be a part of every analysis. These forms are defined
      and distinguished from one another. Each is presented as conforming to a certain
      set to psychological needs in the patient and so as having no overall or general
      significance as to its propriety vis-a-vis the others. As a group these meanings
      necessarily alter the concept of neutrality, rendering it relative to the
      individual patient.

PMID- 9243450
TI  - The view from the tip of the iceberg.
AB  - In recent years there has been a growing interest in refining the technique of
      ego defense analysis. All of these approaches share in common an attempt to work
      closely with the patient's free associations, to interpret at a level that is
      accessible to the patient's consciously observing ego, and to avoid bypassing the
      analysis of the patient's most surface-level resistances in an effort to
      understand unconscious conflict. These innovations reflect a commendable effort
      to work in a way that is rigorously empirical, that respects the patient's
      autonomy, and that minimizes the pressure of the analyst's transferential
      authority in the patient's acceptance of the analyst's interpretations. Despite
      the undeniable value of these technical innovations, such approaches to ego
      defense analysis may inadvertently result in certain overemphases in technique
      that may unnecessarily constrain the analytic process. They may result in a sort
      of obsessive tunnel vision that is overly focused on small details to the
      exclusion of the larger picture. An approach that counterbalances the microscopic
      and the macroscopic analysis of ego defense is recommended.

PMID- 9243453
TI  - Toward an epistemology of clinical psychoanalysis.
AB  - Epistemology emerges from the study of the ways knowledge is gained in the
      different fields of scientific endeavor. Current polemics on the nature of
      psychoanalytic knowledge involve counterposed misconceptions of the nature of
      mind. On one side clinical psychoanalysis is under siege from philosophical "hard
      science" stalwarts who, upholding as the unitary model of scientific knowledge of
      Galilean model of science built around the "well-behaved" variables of mechanics
      and cosmology, argue clinical psychoanalysis does not meet empirical criteria for
      the validation of its claims. On the other side, its empirical character is
      renounced by hermeneuticists who, agreeing with "hard science" advocates on what
      science is, dismiss the animal nature of human beings and hold that clinical
      psychoanalysis is not an empirical science but a "human" interpretive one. Taking
      Adolf Grunbaum's critique as its referent, this paper examines how, by ignoring
      the differences between "exact" and observational science, the "hard science"
      demand for well-behaved variables misconstrues the nature of events in the realm
      of mind. Criteria for an epistemology fit for the facts of clinical
      psychoanalysis as an empirical, observational science of mind are then proposed.

PMID- 9243455
TI  - Inference and evidence in the clinical situation: the analyst's use of the self.
      Panel report.

PMID- 9243454
TI  - General principles of self psychology: a position statement.
AB  - In the more than twenty-five years since Kohut formulated a psychology of the
      self, the basic theory has undergone many revisions and additions. In the course
      of broadening from a focus on narcissism and empathy into a general theory of
      normal and pathological development, self psychology has taken so many different
      directions that the question can be asked, Does self psychology remain
      essentially a single theory with different descriptors--a theory of a self
      selfobject matrix, a theory of intersubjectivity, a theory of motivational
      systems, and so on? A concise statement of general principles is intended to
      contribute to a dialogue between advocates of the views presented here and those
      who hold different views of theory and practice, within and withoutself
      psychology.

PMID- 9243456
TI  - The effect of the environment on intrapsychic conflicts: reality and fantasy in
      modern conflict theory. Panel report.

PMID- 9243457
TI  - Mutual analysis: boundary violation or failed experiment?

PMID- 9243458
TI  - The role of retrograde urethrography in the planning of prostate cancer
      radiotherapy.
AB  - This analysis was performed to examine the role of retrograde urethrography in
      the planning of prostate cancer irradiation. Retrograde urethrograms were
      performed in 91 patients at the time of simulation. The abrupt narrowing of the
      contrast column in the urethra was visualized in each case. The distance between
      the abrupt narrowing of the contrast column and a line connecting the lower poles
      of the ischial tuberosities was measured in each patient. This distance ranged
      from 2 to 33 mm with a mean and median of 14 mm. A review of the literature
      revealed that the abrupt narrowing of the contrast column lies between 5-13 mm
      inferior to the prostate apex as determined by computed tomography (CT), magnetic
      resonance imaging (MRI), and ultrasonography. The prostate apex will be
      adequately covered by placing the inferior edge of the treatment field 15 mm
      below the abrupt narrowing of the contrast column. This technique will result in
      at least 20 mm between the prostate apex and the inferior field edge. Performing
      a retrograde urethrogram at the time of simulation can help prevent geographic
      misses of the prostate gland when delivering radiation for prostate cancer.

PMID- 9243459
TI  - Treatment of adjoining field areas with electron beams of different energy using
      a single central axis.
AB  - The use of a single central axis causes the divergence of radiation at the
      abutting boundaries to be parallel, even in cases for which the abutting boundary
      does not coincide with the beam central axis. Lateral diffusion of scattered
      electrons from an area treated with one energy into the neighboring area is
      reciprocated to provide a smooth change from the dose at4 any given depth near
      the center of one area to that near the center of the other. This allows
      treatment of deep levels of tissue in one portion of a field, while sparing deep
      level structures in an adjacent portion of the field.

PMID- 9243460
TI  - Prostate simulation made easy.
AB  - A combination of computed tomography (CT) scan and retrograde urethrogram is
      routinely employed to simulate treatment portals prior to radiation therapy for
      prostate cancer. These procedures can be performed more efficiently with the use
      of a standard magnitude grid and a prepared urethrogram kit.

PMID- 9243461
TI  - Influence of air inhomogeneities in radiosurgical beams.
AB  - The effect of air inhomogeneity on dose distribution in small diameter beams used
      in stereotactic radiosurgery (SRS) has been investigated. The measurements of the
      surface dose and central axis dose were made for a 6 MV photon beam with a
      diamond detector which has suitable radiologic properties for such measurements.
      Measurements made in a uniform density solid water phantom and in the presence of
      four air gaps indicate significant dose perturbation immediately beyond the air
      solid water interface. The reduction in dose at the surface for a 12.5 mm
      diameter field is 11%, 17%, 23% and 33% for air gap thicknesses of 3, 4.6, 6 and
      9.2 mm, respectively. The corresponding dose reduction for a 25 mm diameter field
      is 3%, 4%, 7% and 13%, respectively. The ratio of the dose with and without air
      inhomogeneity is highly dependent on field diameter and approaches 1.0 as the
      field diameter increases from 12.5 mm to 40 mm. The dose perturbation also
      increases with increase in air inhomogeneity thickness for all field diameters
      investigated. A dose buildup phenomenon is observed beyond the air gap with a
      shallow dmax of approximately 4-6 mm. Beyond the buildup region, a higher dose
      value compared to a homogeneous phantom is observed at all depths due to reduced
      photon attenuation in the air gap. The dose profiles beyond the air gap, measured
      with radiographic films, demonstrate no significant increase in the beam diameter
      but a pronounced broadening of the beam penumbra (80%-20% and 90%-10%) leading to
      enhanced dose outside the primary beam geometric edge and reduced dose inside the
      edge. The dose enhancement outside the beam edge increases with increase in air
      gap thickness.

PMID- 9243462
TI  - An electronic portal imaging device as a physics tool.
AB  - An electronic portal imaging device (EPID) can be used not only to acquire
      megavoltage patient images but also to measure certain radiation beam parameters
      of the linear accelerator. EPID images can be used to verify field junctions,
      center of collimator rotation, or radiation vs. light field coincidence. If the
      EPID images are calibrated in terms of dose rate, an EPID can be applied to beam
      penumbra measurement, collimator transmission determination, or compensator
      verification. Beam parameters measured with EPIDs are in close agreement with
      those measured with film or ionization chamber, making EPIDs reliable physics
      tools for quality control of various beam parameters in radiotherapy.

PMID- 9243463
TI  - Clinical considerations in the use of missing tissue compensators for thoracic
      cases.
AB  - The irregular shape or contour of the patient's surface in the treatment field
      can alter the dose distribution resulting in non-uniformity of dose in the
      treatment volume. Missing tissue compensators have been most commonly used to
      improve this non-uniformity, especially in head and neck, breast, lung and
      supraclavicular regions. Two or three dimensional compensators have been
      typically designed to make the dose uniform at a specific depth. This
      compensation shifts the dose distribution within the treatment volume so that
      some structures may be under or over compensated. This study will examine how
      various thoracic sites are affected by compensators, with and without
      heterogeneity corrections. We have also analyzed the uncertainty in compensated
      dose due to the daily variations in patient repositioning. Computer isodose plans
      using Cobalt-60 gamma rays and 6 and 18 MV X-rays were generated using sagittal
      contours. Results show that superficial sites, like the supraclavicular nodes and
      the spinal cord, do not receive as consistent a dose compensation as the midplane
      sites. In addition, the compensated lung dose increases. Finally, patient
      movement or positioning errors of +/- 1.0 cm causes only a slight change in dose
      distribution.

PMID- 9243464
TI  - Dose uniformity from a computerized three-dimensional tissue compensating system.
AB  - A verification of dose uniformity of the Huestis Compu-Former, a three
      dimensional megavoltage tissue compensator, is presented. Tissue compensators
      were built for three different anthropomorphic phantoms: a head and neck, a
      mantle, and a breast. Film densitometry was used to evaluate the effectiveness of
      the tissue compensators by comparing isodose curves generated for a compensated
      and an uncompensated field. Evaluation of the isodose distributions for the three
      regions confirmed the use of the Compu-Former as a reliable tissue compensating
      system.

PMID- 9243465
TI  - Dose perturbation due to the presence of a prostatic urethral stent in patients
      receiving pelvic radiotherapy: an in vitro study.
AB  - Temporary metallic intraprostatic stent is a new alternative treatment for
      patients with urinary obstructive syndrome caused by prostate cancer. Definitive
      radiotherapy is a treatment of choice for localized prostate cancer. This study
      evaluates in vitro the effect of a urethral intraprostatic metallic stent on the
      dose absorbed by the surrounding tissue. The study was designed to mimic the
      conditions under which the prostatic stent is placed in the body during pelvic
      irradiation. A urethral stent composed of a 50% nickel-50% titanium alloy
      (Uracoil-InStent) was imbedded in material mimicking normal tissue (bolus) at a
      simulated body depth of 10 cm. The distribution of the absorbed dose of
      irradiation was determined by film dosimetry using Kodak X-Omat V film.
      Irradiation was done in a single field at the isocenter of a 6 MV linear
      accelerator with a field size of 7 x 7 cm. The degree of film blackening was in
      direct proportion to the absorbed dose. The measurements showed an increase in
      dose of up to 20% immediately before the stent and a decrease of up to 18%
      immediately after the stent. These changes occurred within a range of 1-3 mm from
      both sides of the stent. In practice, irradiation in prostate cancer is given by
      two pairs of opposed co-axial fields; a total of four fields (Box Technique). The
      dose perturbations are partly cancelled in a pair of opposed beams resulting in a
      net variation of +/- 4%; therefore, the presence of the intraprostatic stent
      should not influence radiotherapy planning for prostate cancer.

PMID- 9243466
TI  - Lateral scatter correction algorithm for percentage depth dose in a large-field
      photon beam.
AB  - Differences between the scatter conditions of dosimetry and treatment situation
      are more important in the case of large-field photon beams than in standard ones.
      In the former, the scattering volume is defined by the phantom cross section; in
      the latter, the radiation field size. Two factors should be considered: the
      thickness and the cross section of the phantom. Both of them have an effect on
      the Percentage Depth Dose (PDD) distribution. In a previous study we addressed
      the influence of backscatter thickness on dose delivered. The aim of this work is
      to measure the effect of cross section phantom on the PDD curves under our TBI
      treatment conditions. Results showed a strong dependence of the PDDs on this
      parameter. A semi-empirical expression has also been derived to calculate (within
      0.5% uncertainty) the Lateral scatter Correction Factor (LCF). The model of LCF
      states a linear dependence on depth whilst slope of these curves depends
      exponentially on distance to the lateral surface. The algorithm is being applied
      to our practical Total Body Irradiation (TBI) procedure.

PMID- 9243467
TI  - Dosimetric analysis and clinical implementation of 6 MV X-ray radiosurgery beam.
AB  - The dosimetric data on tissue maximum ratios (TMR), output factors, off axis
      ratios and beam profiles are presented for small circular fields of diameters
      ranging from 12.5 to 40 mm for 6 MV radiosurgery beam. It is noticed that dmax
      increases as the collimator field size increases. Comparison of our data with the
      published TMR and output factors of similar small circular fields shows that our
      values are higher than those data. Similarities in trend are noticed with the
      published isodose volumes for 1-5 and 10 arcs. Not much variation is seen beyond
      two arcs for 80% isodose volumes for all the field sizes. The variation is small
      in 20% isodose volumes beyond three arcs. Variations are noticed in 5% isodose
      volumes for 12.5 mm diameter collimated beam. Our experience has been exclusively
      with malignant neoplasms. An ideal target volume is covered by 80% isodose volume
      with 3-4 arcs and a single isocenter. Sixteen patients have been treated to date
      at our institution, including one patient with brain metastases, two patients
      with meningiomas, one patient with lymphoma and 12 patients with astrocytomas.
      The majority of tumors have been treated with single isocenter but some as large
      as 7 cm have been treated safely with two isocenters.

PMID- 9243468
TI  - Fetal dose for a patient undergoing mantle field irradiation for Hodgkin's
      disease.
AB  - In order to safely treat a 23 weeks pregnant woman for supradiapharagmatic
      Hodgkin's disease, without compromising the fetus, a custom shielding table was
      constructed and extensive phantom measurements were performed. For 10 MV photons,
      the optimal shielding combination was found to consist of a 5 cm thick lead sheet
      placed onto a 1.25 cm aluminum supporting plate. The structure was placed
      directly above the phantom, over the region corresponding to the woman's abdomen,
      without any intervening air gap. By this means the dose to the fetus from machine
      leakage and collimator scatter was eliminated; the only remaining dose was due to
      in-phantom scatter. The woman was treated using a mantle field to a dose of 35 Gy
      in 20 fractions. The accumulated dose to the woman's uterine fundus and to her
      pubis were monitored with theroluminescent dosimeters. After completion of mantle
      therapy the doses to the fundus and pubis were 10 and 3 cGy, respectively. The
      fetal exposure was thus limited to below 10 cGy, within the zone of fetal
      tolerance. A normal infant was delivered at term.

PMID- 9243470
TI  - The regulatory responsibility over medical uses of radioactive by product
      materials should be transferred from the Nuclear Regulatory Commission.

PMID- 9243469
TI  - Midline shield for radiation therapy of carcinoma of the uterine cervix: should
      it be "midline" or "individualized".
AB  - This study attempts to evaluate the advantage of individualized midline shield
      (IMLS) constructed on the basis of uterine geometry and applicator position in
      terms of the dosimetric consequences to points A-right (AR) and left (AL) as
      compared to standard midline shield (SMLS) in radiation therapy of carcinoma
      cervix. Twenty consecutive patients of carcinoma cervix (Stage I, II and III)
      were treated by external beam radiotherapy (EBRT) (50 Gy/5 weeks/25 fractions)
      and high-dose rate intracavitary brachytherapy (24 Gy/4 weeks/4 fractions)
      prescribed at point A. At the completion of 40 Gy by EBRT (phase I), IMLS (5 cm
      wide) at isocenter was fabricated on the basis of uterine geometry as ascertained
      by a dummy intracavitary application. The remaining 10 Gy of EBRT was delivered
      using IMLS (phase II) to effectively minimize and optimize the dose to point A.
      The dose profiles of IMLS were compared against the corresponding dose profile of
      a 5 cm SMLS and were found to be dependent on the positional variation of AR and
      AL with respect to the midline. With IMLS, the dose to AR and AL for the 10 Gy of
      phase II varied between 21.7-38.87% (30.01 +/- 4.87) and 22.42-35.72% (28.12 +/-
      3.79) respectively. However with SMLS, the AR and AL doses would have ranged from
      22.03% to 77.26% (34.55 +/- 15.94) for AR and from 20.59% to 96.2% (46.93 +/-
      28.15) for AL leading to considerable inhomogeneity. Thus, in protocols
      incorporating midline shield for radiotherapy of carcinoma cervix, IMLS in place
      of SMLS could be preferred for achieving a definitive and homogeneous dose to the
      points AR and AL.

PMID- 9243471
TI  - Determination of the energy fluence of diagnostic x-ray beams from field
      measurements of attenuation curves.
AB  - The use of field measurements of attenuation curves of low-energy x-ray beams as
      a functional description of the beams is presented in this work. The energy
      fluence carried by diagnostic x-ray beams has been determined from A1 attenuation
      measurements made with a quality control ionization chamber for diagnostic x-ray
      equipment and with a low-volume ionization chamber. The obtained values are
      compared with those obtained from a catalog of spectral data for diagnostic x
      rays.

PMID- 9243472
TI  - Three-dimensional computed tomographic reconstruction using a C-arm mounted XRII:
      correction of image intensifier distortion.
AB  - X-ray image intensifiers (XRIIs) have many applications in diagnostic imaging
      including acquisition of near-real-time projection images of the intracranial and
      coronary vasculature. Recently, there has been some interest in using this
      projection data to generate three-dimensional (3-D) computed tomographic (CT)
      reconstructions. The XRII and x-ray tube are rotated around the object, acquiring
      sufficient data for the simultaneous reconstruction of many transverse slices.
      Three-dimensional reconstructions are compromised, however, if the projection
      data is geometrically distorted in any way. Previous studies have shown the
      distortion in XRIIs to be substantial and to be highly angular dependent. In this
      paper, we present a global correction technique which provides a table of
      correction coefficients for an image acquired at any arbitrary angle about the
      patient. The coefficients are generated using a linear least-squares fit between
      the detected and known locations of a grid of small steel beads which is attached
      to the XRII (27 cm nominal diameter). We have performed corrections on 100 images
      obtained during rotation of the gantry through 200 degrees and find that a fifth
      order polynomial provides optimum image distortion reduction (mean residual
      distortion of 0.07 pixels), however, fourth-order polynomials provide sufficient
      distortion reduction for our application (mean residual displacement of 0.1
      pixels). Using sixth-order polynomials does not provide a statistically
      significant reduction in image distortion. The spatial distribution of residual
      distortion did not demonstrate any particular pattern over the face of the XRII.
      Image angle and coefficient angle must be known to within +/- 2 degrees in order
      to keep the mean residual distortion be approximately 0.5 pixels.

PMID- 9243473
TI  - Analysis of the dose-surface histogram and dose-wall histogram for the rectum and
      bladder.
AB  - Dose distribution throughout a hollow organ is represented by either a dose
      surface histogram (DSH) or a dose-wall histogram (DWH). A spherical shell model
      for the bladder and a cylindrical shell model for the rectum were introduced for
      quantifying the difference between the DWH and DSH. The difference was given by
      subtraction of the percent volume of the wall from the percent area of the
      surface for any specific dose level. Taking the dose-grid size and contour
      delineation uncertainties into account, the DSH and DWH calculation errors were
      estimated by simplified formulas. The DSHs and DWHs for the rectum and bladder in
      patients undergoing four-field-prostate treatment and gynecological intracavitary
      brachytherapy were computed with a refined numerical algorithm. Results of the
      analytic models and the numerical calculations demonstrated that the difference
      between the DWH and DSH was small (about 5%) for a fully filled bladder or rectum
      but large (about 10%) for an empty rectum or a contracted bladder. The error of
      DSH was about 3%, which is smaller than that of DWH.

PMID- 9243474
TI  - TG-21 versus TG-25: a comparison for electrons.
AB  - Since 1984, the Radiological Physics Center (RPC) has used the American
      Association of Physicists in Medicine Task Group 21 (TG-21) protocol (absorbed
      dose determination) as the basis of its On-site Dosimetry Review visits to
      institutions participating in the National Cancer Institute's cooperative
      clinical trials. Subsequent to the TG-21 protocol, the Task Group 25 (TG-25)
      report on electron-beam dosimetry was published. The TG-25 report was not
      intended to supercede the TG-21 protocol, but to supplement it for depths other
      than dmax. However, both reports included measurement techniques and data
      regarding the calibration of electron beams. TG-25 was not intended for absolute
      calibrations made clear by the fact that it does not present all of the data
      required for plastic phantom calibrations, i.e., unrestricted stopping power
      ratios. As a result, some confusion has arisen at various institutions as to
      which protocol should be used for machine calibration. In this study, possible
      discrepancies that arise when using TG-21, a version of TG-21 modified by the
      RPC, and TG-25 are compared. The differences in the results are calculated as a
      function of energy (6 and 20 MeV), chamber type (cylindrical or parallel plate),
      and the type of phantom material (water, polystyrene, or acrylic). The largest
      discrepancies noted were between TG-25 and the two TG-21 methods for low-energy
      electrons in either water or polystyrene. The mean difference for all conditions
      was 0.8% with a maximum value of 3.3% in polystyrene. The definition of the
      effective point of measurement; determination of the mean nominal incident energy
      (E0), mean energy at depth (EZ) and most probable energy at the surface (Ep,0)
      for each protocol, and subsequent stopping power ratio, chamber replacement
      factor, and electron fluence correction factor are the major contributors to the
      calculated differences.

PMID- 9243475
TI  - The influence of angular misalignment on fixed-portal intensity modulated
      radiation therapy.
AB  - A method has been developed to estimate potential dose errors due to linear
      accelerator angular setting misalignments of Intensity Modulated Radiation
      Therapy (IMRT) treatments. A first-order approximation to the dose error at a
      point is modeled as the dot product of the dose gradient and the shift vector of
      the point due to the rotational error. The analysis method is applied to a
      previously published set of optimized fluences for a 50 MV IMRT pelvis
      irradiation. Three of the published cases exhibiting a wide range of modulation
      are presented; a rectangular open field, a field optimized for a static multileaf
      collimator defining the portal outline coupled with a single broad bremsstrahlung
      profile modulation, and a fully modulated field using a physical modulator. To
      examine the energy dependence of angle setting errors, the study is repeated
      using the same fluence distributions, but with a dose-spread kernel appropriate
      for a 6 MV photon beam. The collimator angle error is set to 2 degree, and the
      dose error determined with both a centrally located isocenter and an isocenter
      chosen to model a split-field geometry. The dose error due to a 2 degree gantry
      setting error is assessed at a plane 10 cm distal to the isocenter. The
      mathematical form of the dose error due to couch motion is similar to the other
      two errors, so the dose error resulting from a couch angle missetting is not
      presented. The magnitude of the errors is largest for the 6 MV beam, while the
      volume encompassed by the errors is greater for the 50 MV beam. The gantry error
      yields the largest dose error values, with the 6 MV modulated case presenting
      dose errors of greater than 40%.

PMID- 9243476
TI  - Treatment planning for prostate implant with loose seeds.
AB  - A new method of treatment planning for the I-125 and Pd-103 permanent
      interstitial prostate implant is developed, which does not use the traditional
      nomograms but automatically generates optimized source configurations. An
      iterative algorithm is used that places one seed at a step. The volume dose of
      target is calculated at each step to determine the coldest spot where the next
      source is to be placed, so that the dose uniformity of target is best improved as
      source placement proceeds. At each step, the total activity required for the seed
      configuration as so established is calculated by normalizing the minimal dose to
      the prescribed dose. An optimized configuration is the one that takes the
      minimized total activity. Around its minimum the total activity has a very small
      variation with the number of seeds. Consequently multiple clinically acceptable
      seed configurations with similar total activity but different individual
      activities are generated simultaneously. In our computer generated treatment
      plans most of the seeds are distributed in the periphery of the target, similar
      to the Paterson-Parker pattern of a volume implant.

PMID- 9243477
TI  - The optimum intensities for multiple static multileaf collimator field
      compensation.
AB  - A method of determining the optimum beam intensities for compensation using
      multiple static multileaf collimator fields is presented. In this method a
      histogram of the number of beam pixels against beam intensity is generated for
      the intensity-modulated beam (IMB). The intensity of each beam to be used is
      chosen to minimize the mean square deviation between each bin in the histogram
      and the closest beam intensity. This method has been applied to sample IMBs
      possessing one maximum and two maxima. For both cases, the use of uniform beam
      intensity increments is shown to be close to optimal. In the case with two
      maxima, the efficacy of irradiating both peaks simultaneously, rather than
      separately, has been studied and shown to be of potential benefit. The optimum
      intensities for an IMB for breast radiotherapy are also presented.

PMID- 9243478
TI  - Multiple local minima in radiotherapy optimization problems with dose-volume
      constraints.
AB  - The cause of multiple local minima in beam weight optimization problems subject
      to dose-volume constraints is analyzed. Three objective functions were
      considered: (a) maximization of tumor control probability (TCP), (b) maximization
      of the minimum target dose, and (c) minimization of the mean-squared-deviation of
      the target dose from the prescription dose. It is shown that: (a) TCP models
      generally result in strongly quasiconvex objective functions; (b) maximization of
      the minimum target dose results in a strongly quasiconvex objective function; and
      (c) minimizing the root-mean-square dose deviation results in a convex objective
      function. Dose-volume constraints are considered such that, for each region at
      risk (RAR), the volume of tissue whose dose exceeds a certain tolerance dose
      (DTol) is kept equal to or below a given fractional level (VTol). If all RARs
      lack a "volume effect" (i.e., VTol = 0 for all RARs) then there is a single local
      minimum. But if volume effects are present, then the feasible space is possibly
      nonconvex and therefore possibly leads to multiple local minima. These
      conclusions hold for all three objective functions. Hence, possible local minima
      come not from the nonlinear nature of the objective functions considered, but
      from the "either this volume or that volume but not both" nature of the volume
      effect. These observations imply that optimization algorithms for dose-volume
      constraint types of problems should have effective strategies for dealing with
      multiple local minima.

PMID- 9243479
TI  - Implementation of a Monte Carlo dosimetry method for patient-specific internal
      emitter therapy.
AB  - In internal emitter therapy, an accurate description of the absorbed dose
      distribution is necessary to establish an administered dose-response
      relationship, as well as to avoid critical organ toxicity. This work describes
      the implementation of a dosimetry method that accounts for the radionuclide decay
      spectrum, and patient-specific activity and density distributions. The dosimetry
      algorithm is based on a Monte Carlo procedure that simulates photon and electron
      transport and scores energy depositions within the patient. The necessary input
      information may be obtained from a registered set of CT and SPECT or PET images.
      The algorithm provides the absorbed dose rate for the radioactivity distribution
      provided by the SPECT or PET image. The algorithm was benchmarked by reproducing
      dosimetric quantities using the Medical Internal Radionuclide Dose (MIRD)
      Committee's Standard Man phantom and was used to calculate absorbed dose
      distributions for representative case studies.

PMID- 9243480
TI  - Performance evaluation of a diode array for enhanced dynamic wedge dosimetry.
AB  - The performance of a diode array (Profiler) was evaluated by comparing its
      enhanced dynamic wedge (EDW) profiles measured at various depths with point
      measurements using a 0.03 cm3 ionization chamber on a commercial linear
      accelerator. The Profiler, which covers a 22.5 cm width, was used to measure
      larger field widths by concatenating three data sets into a larger field. An
      innovative wide-field calibration technique developed by the manufacturer of the
      device was used to calibrate the individual diode sensitivity, which can vary by
      more than 10%. Profiles of EDW measured with this device at several depths were
      used to construct isodose curves using the percentage depth dose curve measured
      by the ionization chamber. These isodose curves were used to check those
      generated by a commercial treatment planning system. The profiles measured with
      the diode array for both 8 and 18 MV photon beams agreed with those of the
      ionization chamber within a standard deviation of 0.4% in the field (defined as
      80% of the field width) and within a maximum shift of less than 2 mm in the
      penumbra region. The percentage depth dose generally agreed to within 2% except
      in the buildup region. The Profiler was extremely useful as a quality assurance
      tool for EDW and as a dosimetry measurement device with tremendous savings in
      data acquisition time.

PMID- 9243481
TI  - A collection of Physical Activity Questionnaires for health-related research.

PMID- 9243482
TI  - Orbital emphysema as a complication of bungee jumping.
AB  - Bungee jumping is a dangerous sport with increasing popularity in the western
      world. We report the case of a 28-yr-old man who sustained an orbital emphysema
      as a result of bungee jumping. He jumped head first from a 160-ft high bridge
      over a river. At the end of the jump he dived into the water with his head in a
      reclined position. The sudden dive into the water caused an increase of the air
      pressure in the nose and paranasal sinuses, which led to an emphysema of the
      right orbit resulting from a skull fracture not detectable by x-ray. The patient
      was treated with oral antibiotics. Five days later, he had no clinical complaints
      and the ophthalmologic examination was normal. This variation of bungee jumping
      may bear severe risk factors for health in addition to those known from the
      classic jumps.

PMID- 9243483
TI  - Gait adaptations before and after anterior cruciate ligament reconstruction
      surgery.
AB  - Gait analyses of rehabilitated individuals with anterior cruciate ligament (ACL)
      deficiency and reconstruction have identified the final adaptations of increased
      hip extensor torque and hamstring electromyography (EMG) and decreased knee
      extensor torque and quadriceps EMG during stance. The initial adaptations to
      injury and surgery are, however, unknown as are the factors that influence the
      development of the adaptations. Identification of the initial response to injury
      would provide a basis for determining whether the final adaptations are learned
      automatically or if they are the result of a lengthy training period in which
      various factors may affect their development. The purpose of the study was to
      evaluate the initial effects of ACL injury and reconstruction surgery on joint
      kinematics, kinetics, and energetics, during walking. Injured limbs from nine
      subjects with ACL injury were tested 2 wk after injury, and 3 and 5 wk after
      surgery. Ten healthy subjects were tested. Kinematic and ground reaction data
      were collected and combined with inverse dynamics to calculate the joint torques
      and powers. A knee extensor torque throughout most of stance was observed in the
      injured limbs at all test sessions. This result was in conflict with previous
      observations of reduced extensor torque or a flexor torque in rehabilitated
      patients with ACL reconstruction and patients with ACL deficiency. This result
      also differed from the typical midstance extensor then flexor torque in healthy
      control subjects. Trend analysis showed a significant (P < 0.001) change in
      average position at the hip and knee, extensor angular impulse at the hip, and
      positive work done at the hip 3 wk after surgery followed by a partial
      rehabilitation at 5 wk after surgery. Power and work produced at the knee were
      reduced fivefold (P < 0.001) after 5 wk of rehabilitation and did not recover to
      pre-surgical levels. The existence of a long-lasting knee extensor torque 2 wk
      after injury indicated that the adaptation process to ACL deficiency is lengthy,
      requiring many gait cycles, and that numerous factors could be involved in
      learning the adaptations.

PMID- 9243484
TI  - Altered expression of myosin heavy chain in human skeletal muscle in chronic
      heart failure.
AB  - To explore further alterations in skeletal muscle in chronic heart failure (CHF),
      we examined myosin heavy chain (MHC) isoforms from biopsies of the vastus
      lateralis in nine male patients with class II-III (CHF) (left ventricular
      ejection fraction (LVEF) 26 +/- 11%, peak oxygen consumption (peak VO2) 12.6 +/-
      2 mL.kg-1.min-1) and nine age-matched sedentary normal males (NL). The relative
      content of MHC isoforms I, IIa, and IIx was determined by gel electrophoresis as
      follows: The normal sedentary group (NL) had a higher percent of MHC type I when
      compared with the patients (NL 48.4 +/- 7% vs CHF patients 24 +/- 21.6%, P <
      0.05, no difference between MCH IIa (NL 45.1 +/- 10.5% vs CHF 56.0 +/- 12.5%),
      and CHF patients had a higher relative content of MHC type IIx than did the
      normal group (NL 6.5 +/- 9.6% vs CHF 20.0 +/- 12.9%, P < 0.05. Three of nine
      patients had no detectable MHC type I. In patients relative expression of MHC
      type I (%) was related to peak VO2 (r = 0.70, P < 0.05). Our results indicate
      that major alterations in MHC isoform expression are present in skeletal muscle
      in CHF. These alterations parallel previously reported changes in fiber typing
      that may affect contractile function i skeletal muscle and possibly exercise
      performance. The absence of MHC type I in some CHF patients suggests that
      skeletal muscle changes in this disorder are not solely a result of
      deconditioning, buy may reflect a specific skeletal muscle myopathy in this
      disorder.

PMID- 9243486
TI  - Blood flow, lipid oxidation, and muscle glycogen synthesis after glycogen
      depletion by strenuous exercise.
AB  - We studied the interrelationship between blood flow, glycogen synthesis, and
      glucose and lipid utilization in 14 healthy men. A 4-h euglycemic insulin clamp
      with indirect calorimetry and muscle biopsies were done after a glycogen
      depletion (exercise) and after a resting day (control). In spite of the exercise
      induced decrease in leg muscle glycogen content (28% in the basal state, 22%
      after hyperinsulinemia, P < 0.05 in both as compared with the control study),
      basal or insulin stimulated glycogen synthase activity remained unchanged. In the
      basal state, glucose oxidation was 54% lower (P < 0.001) and lipid oxidation 108%
      higher (P < 0.001) after the glycogen depletion as compared with that in the
      control study. During the post-depletion insulin clamp, the glucose oxidation
      rate was 17% lower (P < 0.02) and lipid oxidation 169% higher (P < 0.01), while
      the whole body total glucose disposal was similar in both studies. Baseline
      forearm blood flow was similar and increased equally by over 40% during both
      insulin clamp studies (P < 0.05). Basal glucose extraction after glycogen
      depletion study was one third of that in the control study (P < 0.05). Both basal
      and insulin stimulated leg muscle glycogen content correlated inversely with
      basal forearm blood flow (r = -0.69, P < 0.01 and r = -0.82, P < 0.001,
      respectively) and basal lipid oxidation (r = -0.54, P < 0.05 and r = -0.64, P <
      0.01, respectively) after glycogen depletion. Basal glycogen synthase fractional
      activity correlated positively with forearm blood flow (r = 0.78, P < 0.001) and
      forearm glucose uptake (r = 0.71, P < 0.05) during the insulin infusion. IN
      CONCLUSION: 1) the unchanged insulin sensitivity in the face of glycogen
      depletion is probably a result of increased lipid oxidation, and 2) blood flow is
      related inversely to muscle glycogen content and directly to glycogen synthase
      activity.

PMID- 9243485
TI  - Relationship between aerobic power, blood volume, and thermoregulatory responses
      to exercise-heat stress.
AB  - To clarify the relationship between aerobic power (VO2max), blood volume (BV),
      and thermoregulatory responses to exercise-heat stress, we analyzed the cross
      sectional relationship between the resting BV, plasma volume (PV), erythrocyte
      volume (EV), VO2max, forearm blood flow (FBF), and sweating responses during
      exercise in a hot environment (31 degrees C, 50% relative humidity). Twelve
      college-aged male subjects with a mean maximal oxygen uptake of 48 (range 42-59)
      mL.kg-1.min-1, a mean PV of 54 (range 42-72) mL.kg-1, a mean EV of 31 (range 23
      43) mL.kg-1, and a mean BV of 85 (range 67-115) mL.kg-1 (measured by the Evans
      Blue dye dilution method) performed three sessions of 20-min cycle exercise at
      two levels of intensity (40% and 60% VO2max). The BV, PV and EV correlated
      positively with peak FBF (r = 0.596-0.711, P < 0.05), the increase of FBF in
      response to a unit rise in esophageal temperature (Tes; peak delta FBF/peak delta
      Tes) (r = 0.592-0.656, P < 0.05) and with total sweat loss (TSL) (r = 0.599
      0.634, P < 0.05) during the exercise. The VO2max correlated with TSL during
      exercise at 40% VO2max (r = 0.578, P < 0.05), but not with peak FBF and peak
      delta FBF/peak delta Tes. The VO2max per lean body mass also showed a significant
      positive correlation with BV (r = 0.769, P < 0.01), PV (r = 0.706, P < 0.05), and
      with EV (r = 0.841, P < 0.001). The peak delta FBF/peak delta Tes was correlated
      positively with peak FBF (r = 0.597-0.830, P < 0.05-0.01) and negatively with
      peak Tes (r = 0.641-0.769, P < 0.05-0.01) during the exercise at the two levels.
      However, the chest sweat rate (CSR), TSL, and the increase of CSR in response to
      a unit rise in Tes (peak delta CSR/peak delta Tes) showed no correlation with
      peak Tes during the exercise at the two levels. These findings suggest that 1)
      heat dissipation responses during exercise were related more to blood volume than
      aerobic power and 2) skin blood flow was related more to body temperature than
      sweating responses during exercise under mild heat stress.

PMID- 9243487
TI  - Compartmental shifts of calcium and magnesium as a result of swimming and
      swimming training in rats.
AB  - To describe accurately the mineral changes (Ca and Mg) provoked by swimming, the
      aims of this study were to analyze those tissues that, with regard to their
      mineral content, can better classify individuals performing both swimming until
      exhaustion and swimming as training and to know the shifts of these minerals
      between different tissues after a single session of swimming until exhaustion and
      after training. Wistar rats were distributed into 12 groups, six male and six
      female (N = 10): 1) control rest group (CR); 2) trained rest group (TR); 3)
      control exercise group (CE); 4) trained exercise group (TE); 5) control recovery
      group (CER) and 6) trained recovery group (TER). The most informative tissues of
      Ca and Mg compartmental shifts during exercise have been determined. Discriminant
      analysis selected heart Ca, muscle Ca and bone Ca, bone Mg, erythrocyte Mg, and
      serum Mg as the most significant variables. The animals were classified by means
      of two canonical axes: the first one relates to training situation and sex, and
      the second one shows the special characteristics of trained male rats. Another
      independent discriminant analysis applied to male and female groups separately
      showed that the first canonical axis (control/trained) is basically defined by
      heart Ca, bone Ca, and erythrocyte Mg (male), and by heart Ca, bone Ca, and bone
      Mg (female), while the second axis, related to the exercise situations, is
      defined by the serum Mg levels in both sexes. We think that discriminant analysis
      is a statistical method capable of explaining physiological processes and
      classifying individuals performing exercises of different length. It suggests
      that the homeostasis of Ca and Mg is somewhat different for males and females.
      Serum magnesium must be considered to distinguish exercise situations. The
      analysis of these tissues could inform us about the mineral status of the rats
      and then we could correct possible deficiencies in our research. In this work we
      have only found different mineral redistributions among tissues. The trained
      animals have a better mineral recovery capacity than the untrained ones. Training
      has a different physiological repercussion in male and female rats on the basis
      of their respective maximal swimming times after training and their mineral
      behavior.

PMID- 9243488
TI  - Upright exercise or supine lower body negative pressure exercise maintains
      exercise responses after bed rest.
AB  - Adaptation to bed rest or space flight is accompanied by an impaired ability to
      exercise in an upright position. We hypothesized that a daily, 30-min bout of
      intense, interval exercise in upright posture or supine against lower body
      negative pressure (LBNP) would maintain upright exercise heart rate and
      respiratory responses after bed rest. Twenty-four men (31 +/- 3 yr) underwent 5 d
      of 6 degree head-down tilt: eight performed no exercise (CON), eight performed
      upright treadmill exercise (UPex), and eight performed supine treadmill exercise
      against LBNP at -51.3 +/- 0.4 mm Hg (LBNPex). Submaximal treadmill exercise
      responses (56, 74, and 85% of VO2peak) were measured pre- and post-bed rest. In
      CON, submaximal heart rate, respiratory exchange ratio, and ventilation were
      significantly greater (P < or = 0.05) after bed rest. In UPex and LBNPex,
      submaximal exercise responses were similar pre- and post-bed rest. Our results
      indicate that a daily 30-min bout of intense, interval upright exercise training
      or supine exercise training against LBNP is sufficient to maintain upright
      exercise responses after 5 d of bed rest. These results may have important
      implications for the development of exercise countermeasures during space flight.

PMID- 9243489
TI  - Physical activity and incidence of coronary heart disease in middle-aged women
      and men.
AB  - Few studies of physical activity and coronary heart disease (CHD) have included
      women or blacks. We examined this association in a biracial cohort of 45- to 64
      yr-old adults. We related the sports, leisure, and work indices developed by J.
      A. H. Baecke et al. to CHD incident events (N = 97 in women, N = 223 in men) over
      4-7 yr in the Atherosclerosis Risk in Communities study. The age-, race-, and
      field center-adjusted relative risk of CHD was 0.73 in women and 0.82 in men per
      each standard deviation increment in the sports index (P < 0.05). For the leisure
      index, these relative risks were 0.78 for both sexes (P < 0.05). The work index
      was not associated with CHD. These inverse associations held for non-blacks, but
      there was no association between the sport or leisure indices and CHD among
      blacks. Vigorous sports participation was strongly inversely associated with CHD,
      but an independent contribution of nonvigorous activity (e.g., walking) could not
      be demonstrated conclusively. Adjustment for other risk factors attenuated the
      relative risks, as one might expect if these risk factors mediated any protective
      effect of physical activity. Our findings reinforce evidence that regular
      physical activity should protect women, as well as men, from CHD. Explanations
      for no association among blacks, if real, are needed.

PMID- 9243490
TI  - Associations among physical activity, television watching, and obesity in adult
      Pima Indians.
AB  - It has been suggested that television watching and physical activity are related
      to obesity. This association, however, has been investigated mainly in children.
      This study provided the opportunity to examine the relationship between
      television watching, physical activity, and body mass index in adult Pima
      Indians, a population with a high prevalence of obesity. Hours per day of
      television watched, past-year physical levels (MET-h/wk; leisure and occupational
      combined) and BMI (kg.m-2) were measured in 2452 men and women subjects 21-59 yr
      old. In adults between the ages of 21 and 39 yr, TV and physical activity levels
      were negatively correlated (r = -0.11 for men and -0.10 for women). Weaker
      associations were found between TV and BMI (r = 0.08 for men and 0.04 for women).
      There were no significant relationships among these variables in older adults (49
      59 yr), possibly because of low reported levels of physical activity and TV.
      Multiple linear regression analysis revealed that physical activity and
      television watching in men and activity in women were significantly related to
      BMI. These data suggest that increasing activity levels and decreasing the time
      spent in sedentary behavior such as watching television should both be considered
      as potential intervention strategies in obesity prevention programs.

PMID- 9243491
TI  - Jump distance of dance landings influencing internal joint forces: I. Axial
      forces.
AB  - Knowledge of the magnitude and rate of applying axial forces (AF) during actual
      dance movements is necessary for understanding the etiology of chronic injuries
      and osteoarthritis. The purpose of this study was to investigate the effect of
      jumping distance on component ankle and knee joint AFs generated during the
      landing phase of traveling jumps. Six female dancers performed 10 jumps each at
      30, 60, and 90% maximum jump distance (JD) and 15 jumps ranging from 35 to 100%
      JD. A sagittal view of the right leg landing onto a force platform was filmed.
      Greater ground reaction force maxima, knee flexion, knee and ankle flexion
      velocity, tibial landing angle, net ankle and knee joint moment maxima, ankle and
      knee joint reaction AFs, and quadriceps AFs (QuadAF) peak magnitudes and rates of
      AF application (dFmax/dt) were observed (P < 0.05) at increased JD. The QuadAF
      was a more important determinant of knee AF than joint reaction AF. Increased
      quadriceps force was useful for accommodating impact forces but served to
      increase its contribution to Knee AF, particularly during the later portion of
      the impact phase. High impact situations create significant magnitudes (e.g., 14
      BW) and dFmax/dt of muscle AFs which could contribute to excessive joint wear.

PMID- 9243492
TI  - Jump distance of dance landings influencing internal joint forces: II. Shear
      forces.
AB  - Little is known about shear loading patterns during dance movements. The purpose
      of the study was to investigate the effect of jumping distance (JD) on
      contributors of ankle and knee shear forces (SF) generated during the landing
      phase of traveling jumps. Six female dancers performed 10 trials each at 30, 60,
      and 90% maximum jump distance (JD) and 15 jumps ranging from 35 to 100% JD. A
      sagittal view of the right leg landing onto a force platform was filmed using a
      high-speed cine camera. Greater ankle and knee joint reaction shear forces (JRSF)
      and quadriceps SF (QuadSF) were observed (P < 0.05) at increased JD. Although the
      triceps surae SF (TriSurSF) also increased at greater JD for all but one
      participant, the effect on minimizing the increase in the ankle SF was minor. The
      peak QuadSF magnitude and rate of loading were always greater than the
      corresponding knee JRSF variables. However, the increased QuadSF that occurred at
      longer jumps led to increased knee SF for only half of the participants.

PMID- 9243493
TI  - Cardiorespiratory response to exercise in elite Sherpa climbers transferred to
      sea level.
AB  - Himalayan Sherpas are well known for their extraordinary adaptation to high
      altitude and some of them for their outstanding physical performance during
      ascents to the highest summits. To cast light on this subject, we evaluated the
      cardiorespiratory response during exercise at sea level of six of the most
      acknowledged Sherpa climbers, mean age (+/- SD) 37 (+/- 7) yr old. Continuous
      electrocardiogram and breath-by-breath pulmonary gas exchange until exhaustion
      were obtained by following the Bruce protocol. We detected a maximal oxygen
      uptake (VO2max) of 66.7 (+/- 3.7) mL-min-1.kg-1, maximal cardiac frequency of 199
      (+/- 7) beats.min-1, and ventilatory anaerobic threshold at 62 (+/- 4) % of
      VO2max. These factors could help to explain the greater performance level shown
      by several elite climbers of this ethnic group. The high functional reserve
      demonstrated by this very select group of highlanders could be associated with
      natural selection and with special physiological adaptations probably induced by
      long-training in a hostile environment.

PMID- 9243494
TI  - Improved running performance in hot humid conditions following whole body
      precooling.
AB  - On two separate occasions, eight subjects controlled speed to run the greatest
      distance possible in 30 min in a hot, humid environment (ambient temperature 32
      degrees C, relative humidity 60%). For the experimental test (precooling),
      exercise was preceeded by cold-water immersion. Precooling increased the distance
      run by 304 +/- 166 m (P < 0.05). Precooling decreased the pre-exercise rectal and
      mean skin temperature by 0.7 degrees C and 5.9 degrees C, respectively (P <
      0.05). Rectal and mean skin temperature were decreased up to 20 and 25 min during
      exercise, respectively (P < 0.05). Mean body temperature decreased from 36.5 +/-
      0.1 degrees C to 33.8 +/- 0.2 degrees C following precooling (P < 0.05) and
      remained lower throughout exercise (P < 0.01) and at the end of exercise (by 0.8
      degrees C; P < 0.05). The rate of heat storage at the end of exercise increased
      from 113 +/- 45 to 249 +/- 55 W.m-2 (P < 0.005). Precooling lowered the heart
      rate at rest (13%), 5 (9%), and 10 min (10%) exercise (P < 0.05) and increased
      the end of exercise blood lactate from 4.9 +/- 0.5 to 7.4 +/- 0.9 mmol.L-1 (P <
      0.01). The VO2 at 10 and 20 min of exercise and total body sweating are not
      different between tests. In conclusion, water immersion precooling increased
      exercise endurance in hot, humid conditions with an enhanced rate of heat storage
      and decreased thermoregulatory strain.

PMID- 9243495
TI  - Energy expenditure of swimmers during high volume training.
AB  - The purpose of this study was to examine the total energy expenditure (TEE) of
      swimmers during high volume training (17.5 +/- 1.0 km.d-1) using the doubly
      labeled water method. Five female swimmers (age, 19 +/- 1 yr; height, 178.3 +/-
      2.2 cm; weight 65.4 +/- 1.6 kg) were administered a dose of 2H2(18)O and
      monitored for 5 days. Training consisted of two sessions per day, lasting a total
      of 5-6 h. Energy intake (EI) was calculated from dietary records. Resting energy
      expenditure (REE) was measured on a non-training day and averaged 7.7 +/- 0.5
      MJ.d-1 (1840 +/- 130 kcal.d-1). There were no changes in body weight (day 1, 65.4
      +/- 1.6; day 5, 65.2 +/ 1.5 kg) over the measurement period. TEE of the swimmers
      during the training period averaged 23.4 +/- 2.1 MJ.d-1 (5593 +/- 495 kcal.d-1).
      EI averaged 13.1 +/- 1.0 MJ.d-1 (3136 +/- 227 kcal.d-1), implying a negative
      energy balance of 43 +/- 2%. TEE expressed as a multiple of REE was 3.0 +/- 0.2.
      The results of this investigation describe the total energy demands of high
      volume swimming training, which may be used to address the dietary concerns of
      the competitive swimming athlete.

PMID- 9243496
TI  - Wet bulb globe temperature index and performance in competitive distance runners.
AB  - In 1974 two sets of heat stress guidelines, each based on the wet bulb globe
      temperature (WBGT) index, were designed for men's National Collegiate Athletic
      Association (NCAA) Championship Division I distance running competitions. One set
      of guidelines was established to minimize the chance of heat injury during
      distance running events. A second set was designed to predict heat stress related
      performance decrements. During the time the heat injury guidelines were used
      (1974-1993), no heat injuries were reported. The purpose of this study was to
      assess the accuracy of the performance decrement guidelines and determine whether
      the WBGT indices were linearly related to men's championship distance running
      performance. WBGT index data were collected during the 1500-, 3000-steeplechase
      (SC), 5000-, and 10,000-m events at men's NCAA Division I Track and Field
      Championships held from 1974 to 1981 (excluding 1975). These data were compared
      to the average running performance of the top six finishers in each event.
      Analysis of the accuracy of the NCAA performance decrement guidelines revealed
      four unexpected performances out of 28 predictions. Pearson product-moment
      correlation and linear regression analyses between the WBGT indices and
      performance revealed statistically significant linear relationships for the 3000
      SC and 10,000-m events (P < 0.05). A significant linear relationship was also
      found when the 1500-, 3000-SC, 5000-, and 10,000-m results were pooled (P <
      0.05). In conclusion, the NCAA guidelines were effective in preventing heat
      injury and fairly successful in predicting performance. However, a linear
      relationship between WBGT indices and distance running performance did not exist
      in all running events.

PMID- 9243497
TI  - Validity of bioelectrical impedence equations for estimating fat-free weight in
      high school female gymnasts.
AB  - The present study examined the validity of bioelectrical impedence (BIA)
      equations for estimating fat-free weight (FFW) in female gymnasts by comparing
      the values to those obtained from underwater weighing (UWW). Ninety-seven female
      Caucasian high school gymnasts (mean age +/- SD = 15.7 +/- 1.1 yr) participated
      in the study. FFW from UWW was calculated from percent fat using the revised
      formula of Brozek et al. (mean FFW +/- SD = 43.8 +/- 4.5 kg) and the age-specific
      constants of Lohman (mean FFW +/- SD = 44.8 +/- 4.6 kg). Cross-validation
      analyses included examination of the constant error (CE), SEE, r, and total error
      (TE). The results indicated similar trends between equations when based on either
      the Brozek or Lohman conversions; however, the CE, SEE, and TE values were
      consistently lower for the majority of the equations using the revised formula of
      Brozek et al. Based upon the results of the cross-validation analyses, the
      equation of Houtkooper et al. and the interlaboratory equations of Van Loan et
      al. and Lohman, which resulted in identical TE values of 2.4 kg are recommended
      for use with young high school gymnasts.

PMID- 9243498
TI  - Predictive accuracy of BIA equations for estimating fat-free mass of black men.
AB  - This study assessed the predictive accuracy of previously published bioelectrical
      impedence analysis (BIA) equations in estimating the fat-free mass (FFM) of black
      men, 19 to 50 years. The reference method was hydrostatic weighing (HW) at
      residual lung volume. Body density (Db) was converted to relative body fat (%BF)
      for calculation of FFMHW using the Schutte et al. equation. Resistance and
      reactance were measured with a Valhalla bioimpedance analyzer. Age-specific,
      generalized, and fatness-specific BIA equations were cross validated using
      regression analysis. The Segal fatness-specific equations were modified using a
      method recommended by Stolarczyk. All of the equations significantly (P < 0.05)
      underestimated the average reference measure of FFMHW. However, the
      underestimation of FFM for the modified Segal fatness-specific equation was
      relatively small (-1.8 kg) and not likely to have much clinical significance.
      Furthermore, this equation had a high correlation with reference FFMHW (ry,y' =
      0.97), low prediction errors (SEE = 2.1 kg; E = 2.7 kg), and accurately estimated
      the FFM within +/- 3.5 kg for 78% of the individuals in the sample. Thus, we
      recommend using the modified fatness-specific BIA equation for estimating the FFM
      of black men.

PMID- 9243499
TI  - Bet1p activates the v-SNARE Bos1p.
AB  - Bet1p is a type II membrane protein that is required for vesicular transport
      between the endoplasmic reticulum and Golgi complex in the yeast Saccharomyces
      cerevisiae. A domain of Bet1p, that shows potential to be involved in a coiled
      coil interaction, is homologous to a region of the neuronal protein SNAP-25.
      Here, we used in vitro binding studies to demonstrate that Bet1p plays a role in
      potentiating soluble NSF attachment protein receptor (SNARE) interactions.
      Mutational analysis points to the coiled-coil region as necessary for Bet1p
      function, and circular dichroism experiments support this theory. In vitro
      binding studies were also used to demonstrate that a direct interaction between
      Bet1p and Bos1p is required for the efficient interaction of the vesicle SNARE
      with its SNARE target. Genetic studies suggest that the interactions of Bet1p
      with Bos1p are regulated by the small GTP-binding protein Ypt1p.

PMID- 9243500
TI  - The role of the Src homology domains in morphological transformation by v-src.
AB  - The Src homology (SH2 and SH3) domains of v-Src are required for transformation
      of Rat-2 cells and for wild-type (morphr) transformation of chicken embryo
      fibroblasts (CEFs). We report herein that the N-terminal domains of v-Src, when
      expressed in trans, cannot complement the transformation defect of a deletion
      mutant lacking the "unique," SH3, and SH2 regions. However, the same regions of
      Src can promote transformation when translocated to the C terminus of v-Src,
      although the transformation of CEFs is somewhat slower. We conclude that the SH3
      and SH2 domains must be present in cis to the catalytic domain to promote
      transformation but that transformation is not dependent on the precise
      intramolecular location of these domains. In CEFSs and in Rat-2 cells, the
      expression of wild-type v-Src results in tyrosine phosphorylation of proteins
      that bind to the v-Src SH3 and SH2 domains in vitro; mutations in the SH2 or SH3
      and SH2 domains prevent the phosphorylation of these proteins. These findings are
      most consistent with models in which the SH3 and SH2 domains of v-Src directly or
      indirectly target the catalytic domain to substrates involved in transformation.
      However, the N-terminal domains of v-Src can promote tyrosine phosphorylation of
      certain proteins, in particular p130Cas, even when expressed in the absence of
      the catalytic domain, indicating that the N-terminal domains of v-Src have
      effects that are independent of the catalytic domain.

PMID- 9243501
TI  - Ionizing radiation induces apoptosis and elevates cyclin A1-Cdk2 activity before
      but not after the midblastula transition in Xenopus.
AB  - After the twelfth cell division in Xenopus embryos, zygotic gene transcription is
      activated, cells become motile, and cell division becomes asynchronous. This
      developmental change is termed the midblastula transition. High doses of gamma
      irradiation (gamma-IR) before the midblastula transition induced apoptotic cell
      death and increased the levels of cyclin A1 and cyclin A1-Cdk2 activity. The
      addition of recombinant cyclin A1-Cdk2 induced the formation of apoptotic nuclei
      in Xenopus egg extracts, suggesting a role for cyclin A1-Cdk2 in apoptosis.
      Hallmarks of apoptosis, such as internucleosomal DNA fragmentation, pyknotic and
      uniformly condensed nuclei, and loss of intercellular attachments, were evident
      in embryos exposed to gamma-IR before the midblastula transition. Apoptotic cells
      accumulated in the blastocoel, suggesting that before the midblastula transition
      Xenopus embryos use apoptosis to eliminate cells containing damaged DNA. However,
      embryos treated with the same dose of gamma-IR after the midblastula transition
      developed normally and exhibited no signs of apoptosis, no change in cyclin A1
      level, and no increase in cyclin A1-Cdk2 activity. These results indicate that
      there is a change in the response to DNA damage at the midblastula transition in
      Xenopus embryos.

PMID- 9243502
TI  - The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled
      bodies.
AB  - TFIIH is a general transcription factor for RNA polymerase II that in addition is
      involved in DNA excision repair. TFIIH is composed of eight or nine subunits and
      we show that at least four of them, namely cdk7, cyclin H, MAT1, and p62 are
      localized in the coiled body, a distinct subnuclear structure that is
      transcription dependent and highly enriched in small nuclear ribonucleoproteins.
      Although coiled bodies do not correspond to sites of transcription, in vivo
      incorporation of bromo-UTP shows that they are surrounded by transcription foci.
      Immunofluorescence analysis using antibodies directed against the essential
      repair factors proliferating cell nuclear antigen and XPG did not reveal labeling
      of the coiled body in either untreated cells or cells irradiated with UV light,
      arguing that coiled bodies are probably not involved in DNA repair mechanisms.
      The localization of cyclin H in the coiled body was predominantly detected during
      the G1 and S-phases of the cell cycle, whereas in G2 coiled bodies were very
      small or not detected. Finally, both cyclin H and cdk7 did not colocalize with
      P80 coilin after disruption of the coiled body, indicating that these proteins
      are specifically targeted to the small nuclear ribonucleoprotein-containing
      domain.

PMID- 9243503
TI  - Mitogen-activated protein kinase/extracellular signal-regulated kinase 2
      regulates cytoskeletal organization and chemotaxis via catalytic and microtubule
      specific interactions.
AB  - The extracellular signal-regulated kinases (ERKs) 1 and 2 are mitogen-activated
      protein kinases that act as key components in a signaling cascade linking growth
      factor receptors to the cytoskeleton and the nucleus. ERK2 mutants have been used
      to alter cytoskeletal regulation in Chinese hamster ovary cells without affecting
      cell growth or feedback signaling. Mutation of the unique loop L6 (residues 91
      95), which is in a portion of the molecule that is cryptic upon the binding of
      ERK2 to the microtubules (MTs), generated significant morphological alterations.
      Most notable phenotypes were observed after expression of a combined mutant
      incorporating changes to both L6 and the TEY phosphorylation lip, including a 70%
      increase in cell spreading. Actin stress fibers in these cells, which normally
      formed a single broad parallel array, were arranged in three or more orientations
      or in fan-like arrays. MTs, which ordinarily extend longitudinally from the
      centrosome, spread radially, covering a larger surface area. Single, but not the
      double, mutations of the Thr and Tyr residues of the TEY phosphorylation lip
      caused a ca. 25% increase in cell spreading, accompanied by a threefold increase
      in chemotactic cell migration. Mutation of Lys-52 triggered a 48% increase in
      cell spreading but no alteration to chemotaxis. These findings suggest that wild
      type ERK2 inhibits the organization of the cytoskeleton, the spreading of the
      cell, and chemotactic migration. This involves control of the orientation of
      actin and MTs and the positioning of focal adhesions via regulatory interactions
      that may occur on the MTs.

PMID- 9243504
TI  - Mitochondrial transmission during mating in Saccharomyces cerevisiae is
      determined by mitochondrial fusion and fission and the intramitochondrial
      segregation of mitochondrial DNA.
AB  - To gain insight into the process of mitochondrial transmission in yeast, we
      directly labeled mitochondrial proteins and mitochondrial DNA (mtDNA) and
      observed their fate after the fusion of two cells. To this end, mitochondrial
      proteins in haploid cells of opposite mating type were labeled with different
      fluorescent dyes and observed by fluorescence microscopy after mating of the
      cells. Parental mitochondrial protein markers rapidly redistributed and
      colocalized throughout zygotes, indicating that during mating, parental
      mitochondria fuse and their protein contents intermix, consistent with results
      previously obtained with a single parentally derived protein marker. Analysis of
      the three-dimensional structure and dynamics of mitochondria in living cells with
      wide-field fluorescence microscopy indicated that mitochondria form a single
      dynamic network, whose continuity is maintained by a balanced frequency of
      fission and fusion events. Thus, the complete mixing of mitochondrial proteins
      can be explained by the formation of one continuous mitochondrial compartment
      after mating. In marked contrast to the mixing of parental mitochondrial proteins
      after fusion, mtDNA (labeled with the thymidine analogue 5-bromodeoxyuridine)
      remained distinctly localized to one half of the zygotic cell. This observation
      provides a direct explanation for the genetically observed nonrandom patterns of
      mtDNA transmission. We propose that anchoring of mtDNA within the organelle is
      linked to an active segregation mechanism that ensures accurate inheritance of
      mtDNA along with the organelle.

PMID- 9243505
TI  - Determination of floral organ identity by Arabidopsis MADS domain homeotic
      proteins AP1, AP3, PI, and AG is independent of their DNA-binding specificity.
AB  - The MADS domain homeotic proteins APETALA1 (AP1), APETALA3 (AP3), PISTILLATA
      (PI), and AGAMOUS (AG) combinatorially specify the identity of Arabidopsis floral
      organs. AP1/AP1, AG/AG, and AP3/PI dimers bind to similar CArG box sequences;
      thus, differences in DNA-binding specificity among these proteins do not seem to
      be the origin of their distinct organ identity properties. To assess the overall
      contribution that specific DNA binding could make to their biological
      specificity, we have generated chimeric genes in which the amino-terminal half of
      the MADS domain of AP1, AP3, PI, and AG was substituted by the corresponding
      sequences of human SRF and MEF2A proteins. In vitro DNA-binding assays reveal
      that the chimeric proteins acquired the respective, and distinct, DNA-binding
      specificity of SRF or MEF2A. However, ectopic expression of the chimeric genes
      reproduces the dominant gain-of-function phenotypes exhibited by plants
      ectopically expressing the corresponding Arabidopsis wild-type genes. In
      addition, both the SRF and MEF2 chimeric genes can complement the pertinent ap1
      1, ap3-3, pi-1, or ag-3 mutations to a degree similar to that of AP1, AP3, PI,
      and AG when expressed under the control of the same promoter. These results
      indicate that determination of floral organ identity by the MADS domain homeotic
      proteins AP1, AP3, PI, and AG is independent of their DNA-binding specificity. In
      addition, the DNA-binding experiments show that either one of the two MADS
      domains of a dimer can be sufficient to confer a particular DNA-binding
      specificity to the complex and that sequences outside the amino-terminal basic
      region of the MADS domain can, in some cases, contribute to the DNA-binding
      specificity of the proteins.

PMID- 9243506
TI  - Syntaxin 6 functions in trans-Golgi network vesicle trafficking.
AB  - The specific transfer of vesicles between organelles is critical in generating
      and maintaining the organization of membrane compartments within cells. Syntaxin
      6 is a recently discovered member of the syntaxin family, whose constituents are
      required components of several vesicle trafficking pathways. To better understand
      the function of syntaxin 6, we generated a panel of monoclonal antibodies that
      specifically recognize different epitopes of the protein. Immunoelectron
      microscopy shows syntaxin 6 primarily on the trans-Golgi network (TGN), where is
      partially colocalizes with the TGN adapter protein AP-1 on clathrin-coated
      membranes. Additional label is present on small vesicles in the vicinity of
      endosome-like structures. Immunoprecipitation of syntaxin 6 revealed that it is
      present in a complex or complexes with alpha-soluble NSF attachment protein,
      vesicle-associated membrane protein 2, or cellubrevin and a mammalian homologue
      of VPS45, which is a member of the sec1 family implicated in Golgi to prevacuolar
      compartment trafficking in yeast. We show that mammalian VPS45 is found in
      multiple tissues, is partially membrane associated, and is enriched in the Golgi
      region. Converging lines of evidence suggest that syntaxin 6 mediates a TGN
      trafficking event, perhaps targeting to endosomes in mammalian cells.

PMID- 9243507
TI  - A novel a-factor-related peptide of Saccharomyces cerevisiae that exits the cell
      by a Ste6p-independent mechanism.
AB  - Many secreted signaling molecules are synthesized as precursors that undergo
      multiple maturation steps to generate their mature forms. The Saccharomyces
      cerevisiae mating pheromone a-factor is a C-terminally isoprenylated and
      carboxylmethylated dodecapeptide that is initially synthesized as a larger
      precursor containing 36 or 38 amino acids. We have previously shown that the
      maturation of a-factor occurs by an ordered biogenesis pathway involving 1) three
      C-terminal modification steps, 2) two N-terminal proteolytic processing events,
      and 3) a nonclassical export mechanism mediated by the ATP-binding-cassette (ABC)
      transporter Ste6p. In the present study, we demonstrate that an unexpected and
      abundant a-factor-related peptide (AFRP) exists in the culture fluid of MATa
      cells and that its biogenesis is integrally related to that of mature a-factor
      itself. We show by purification followed by mass spectrometry that AFRP
      corresponds to the C-terminal 7 amino acids (VFWDPAC) of mature a-factor
      (YIIKGVFWDPAC), including both the farnesyl- and carboxylmethylcysteine
      modifications. The formation and export of AFRP displays three striking features.
      First, we show that AFRP is produced intracellularly and that mutants (ste24 and
      axl1) that cannot produce mature a-factor due to an N-terminal processing defect
      are nevertheless normal for AFRP production. Thus, AFRP is not derived from
      mature a-factor but, instead, from the P1 form of the a-factor precursor. Second,
      fusion constructs with foreign amino acids substituted for authentic a-factor
      residues still yield AFRP-sized molecules; however, the composition of these
      corresponds to the altered residues instead of to AFRP residues. Thus, AFRP may
      be generated by a sequence-dependent but length-specific proteolytic activity.
      Third, a-factor and AFRP use distinct cellular machinery for their secretion.
      Whereas a-factor export is Ste6p-dependent, AFRP is secreted normally even in a
      ste6 deletion mutant. Thus, AFRP may exit the cell by another ATP-binding
      cassette transporter, a different type of transporter altogether, or possibly by
      diffusion. Taken together, these studies indicate that the biogenesis of AFRP
      involves novel mechanisms and machinery, distinct from those used to generate
      mature a-factor. Because AFRP neither stimulates nor inhibits mating or a-factor
      halo activity, its function remains an intriguing question.

PMID- 9243508
TI  - Two glucose sensing/signaling pathways stimulate glucose-induced inactivation of
      maltose permease in Saccharomyces.
AB  - Glucose is a global metabolic regulator in Saccharomyces. It controls the
      expression of many genes involved in carbohydrate utilization at the level of
      transcription, and it induces the inactivation of several enzymes by a
      posttranslational mechanism. SNF3, RGT2, GRR1 and RGT1 are known to be involved
      in glucose regulation of transcription. We tested the roles of these genes in
      glucose-induced inactivation of maltose permease. Our results suggest that at
      least two signaling pathways are used to monitor glucose levels. One pathway
      requires glucose sensor transcript and the second pathway is independent of
      glucose transport. Rgt2p, which along with Snf3p monitors extracellular glucose
      levels, appears to be the glucose sensor for the glucose-transport-independent
      pathway. Transmission of the Rgt2p-dependent signal requires Grr1p. RGT2 and GRR1
      also play a role in regulating the expression of the HXT genes, which appear to
      be the upstream components of the glucose-transport-dependent pathway regulating
      maltose permease inactivation. RGT2-1, which was identified as a dominant
      mutation causing constitutive expression of several HXT genes, causes
      constitutive proteolysis of maltose permease, that is, in the absence of glucose.
      A model of these glucose sensing/signaling pathways is presented.

PMID- 9243509
TI  - Mss4 does not function as an exchange factor for Rab in endoplasmic reticulum to
      Golgi transport.
AB  - Mss4 and its yeast homologue, Dss4, have been proposed to function as guanine
      nucleotide exchange factors (GEFs) for a subset of Rab proteins in the secretory
      pathway. We have previously shown that Rab1A mutants defective in GTP-binding
      potently inhibit endoplasmic reticulum to Golgi transport, presumably by
      sequestering an unknown GEF regulating its function. We now demonstrate that
      these mutants stably associate with Mss4 both in vivo and in vitro and that Mss4
      effectively neutralizes the inhibitory activity of the Rab1A mutants. An
      equivalent Rab3A mutant (Rab3A[N135I]), a Rab protein specifically involved in
      regulated secretion at the cell surface, associates with Mss4 as efficiently as
      the Rab1A[N124I] mutant. Although Rab3A[N135I] prevents the ability of Mss4 to
      neutralize the inhibitory effects of Rab1A mutants on transport, it has no effect
      on Rab1 function or endoplasmic reticulum to Golgi transport. Furthermore,
      quantitative immunodepletion of Mss4 fails to inhibit transport in vitro. We
      conclude that Mss4 and its yeast homologue, Dss4, are not GEFs mediating
      activation of Rab, but rather, they interact with the transient guanine
      nucleotide-free state, defining a new class of Ras-superfamily GTPase effectors
      that function as guanine nucleotide-free chaperones (GFCs).

PMID- 9243510
TI  - The ankyrin repeat-containing protein Akr1p is required for the endocytosis of
      yeast pheromone receptors.
AB  - The Saccharomyces cerevisiae a-factor receptor (Ste3p) requires its C-terminal
      cytoplasmic tail for endocytosis. Wild-type receptor is delivered to the cell
      surface via the secretory pathway but remains there only briefly before being
      internalized and delivered to the vacuole for degradation. Receptors lacking all
      or part of the cytoplasmic tail are not subject to this constitutive endocytosis.
      We used the cytoplasmic tail of Ste3p as bait in the two-hybrid system in an
      effort to identify other proteins involved in endocytosis. One protein identified
      was Akr1p, an ankyrin repeat-containing protein. We applied three criteria to
      demonstrate that Akr1p is involved in the constitutive endocytosis of Ste3p.
      First, when receptor synthesis is shut off, akr1 delta cells retain the ability
      to mate longer than do AKR1 cells. Second, Ste3p half-life is increased by
      greater than 5-fold in akr1 delta cells compared with AKR1 cells. Third, after a
      pulse of synthesis, newly synthesized receptor remains at the cell surface in
      akr1 delta mutants, whereas it is rapidly internalized in AKR1 cells.
      Specifically, in akr1 delta mutants, newly synthesized receptor is accessible to
      exogenous protease, and by indirect immunofluorescence, the receptor is located
      at the cell surface. akr1 delta cells are also defective for endocytosis of the
      alpha-factor receptor (Ste2p). Despite the block to constitutive endocytosis
      exhibited by akr1 delta cells, they are competent to carry out ligand-mediated
      endocytosis of Ste3p. In contrast, akr1 delta cells cannot carry out ligand
      mediated endocytosis of Ste2p. We discuss the implications for Akr1p function in
      endocytosis and suggest a link to the regulation of ADP-ribosylation proteins
      (Arf proteins).

PMID- 9243511
TI  - Thrombospondin-1, a natural inhibitor of angiogenesis, regulates platelet
      endothelial cell adhesion molecule-1 expression and endothelial cell
      morphogenesis.
AB  - Expression of thrombospondin-1 (TS1) in polyoma middle-sized T (tumor)
      transformed mouse brain endothelial cells (bEND.3) restores a normal phenotype
      and suppresses their ability to form hemangiomas in mice. We show that TS1
      expression results in complete suppression of platelet-endothelial cell adhesion
      molecule-1 (PECAM-1) expression and altered cell-cell interactions in bEND.3
      cells. To further investigate the role of PECAM-1 in regulation of endothelial
      cell-cell interactions and morphogenesis, we expressed human (full length) or
      murine (delta 15) PECAM-1 isoforms in TS1-transfected bEND.3 (bEND/TS) cells.
      Expression of either human or murine PECAM-1 resulted in an enhanced ability to
      organize and form networks of cords on Matrigel, an effect that was specifically
      blocked by antibodies to PECAM-1. Anti-PECAM-1 antibodies also inhibited tube
      formation in Matrigel by normal human umbilical vein endothelial cells. However,
      PECAM-1-transfected bEND/TS cells did not regain the ability to form hemangiomas
      in mice and the expressed PECAM-1, unlike the endogenous PECAM-1 expressed in
      bEND.3 cells, failed to localize to sites of cell-cell contact. This may be, in
      part, attributed to the different isoforms of PECAM-1 expressed in bEND.3 cells.
      Using reverse transcription-polymerase chain reaction, we determined that bEND.3
      cells express mRNA encoding six different PECAM-1 isoforms, the isoform lacking
      both exons 14 and 15 (delta 14&15) being most abundant. Expression of the murine
      delta 14&15 PECAM-1 isoform in bEND/TS cells resulted in a similar phenotype to
      that described for the full-length human or murine delta 15 PECAM-1 isoform. The
      delta 14&15 isoform, despite the lack of exon 14, failed to localize to sites of
      cell-cell contact even in clones that expressed it at very high levels. Thus,
      contrary to recent reports, lack of exon 14 is not sufficient to result in
      junctional localization of PECAM-1 isoforms in bEND/TS cells.

PMID- 9243512
TI  - Evidence for a recycling role for Rab7 in regulating a late step in endocytosis
      and in retention of lysosomal enzymes in Dictyostelium discoideum.
AB  - The mammalian small molecular weight GTPase Rab7 (Ypt7 in yeast) has been
      implicated in regulating membrane traffic at postinternalization steps along the
      endosomal pathway. A cDNA encoding a protein 85% identical at the amino acid
      level to mammalian Rab7 has been cloned from Dictyostelium discoideum.
      Subcellular fractionation and immunofluorescence microscopy indicated that Rab7
      was enriched in lysosomes, postlysosomes, and maturing phagosomes. Cell lines
      were generated that overexposed Rab7 wild-type (WT), Rab7 Q67L (constitutively
      active form), and Rab7 T22N (dominant negative form) proteins. The Rab7 T22N cell
      line internalized fluid phase markers and latex beads (phagocytosis) at one-third
      the rate of control cells, whereas Rab7 WT and Rab7 Q67L cell lines were normal
      in uptake rates but exocytosed fluid phase faster than control cells. In
      contrast, fluid phase markers resided in acidic compartments for longer periods
      of time and were more slowly exocytosed from Rab7 T22N cells as compared with
      control cells. Light microscopy indicated that Rab7-expressing cell lines
      contained morphologically altered endosomal compartments. Compared with control
      cells, Rab7 WT- and Rab7 Q67L-expressing cells contained a reduced number of
      vesicles, the size of postlysosomes (> 2.5 microns) and an increased number of
      smaller vesicles, many of which were nonacidic; in control cells, > 90% of the
      smaller vesicles were acidic. In contrast, Rab7 T22N cells contained an increased
      proportion of large acidic vesicles relative to nonacidic vesicles. Radiolabel
      pulse-chase experiments indicated that all of the cell lines processed and
      targeted lysosomal alpha-mannosidase normally, indicating the lack of a
      significant role for Rab7 in the targeting pathway; however, retention of mature
      lysosomal hydrolases was affected in Rab7 WT and Rab7 T22N cell lines. Contrary
      to the results observed for the fluid phase efflux experiments, Rab7 T22N cells
      oversecreted alpha-mannosidase, whereas Rab7 WT cells retained this hydrolase as
      compared with control cells. These data support a model that Rab7 may regulate
      retrograde transport of lysosomal enzymes and the V-type H(+)-ATPase from
      postlysosomes to lysosomes coupled with the efficient release of fluid phase from
      cells.

PMID- 9243513
TI  - The yeast actin-related protein Arp2p is required for the internalization step of
      endocytosis.
AB  - The Saccharomyces cerevisiae actin-related protein Arp2p is an essential
      component of the actin cytoskeleton. We have tested its potential role in the
      endocytic and exocytic pathways by using a temperature-sensitive allele, arp2-1.
      The fate of the plasma membrane transporter uracil permease was followed to
      determine whether Arp2p plays a role in the endocytic pathway. Inhibition of
      normal endocytosis as revealed by maintenance of active uracil permease at the
      plasma membrane and strong protection against subsequent vacuolar degradation of
      the protein were observed in the mutant at the restrictive temperature.
      Furthermore, arp2-1 cells accumulated ubiquitin-permease conjugates, formed prior
      to internalization. These effects were also visible at permissive temperature,
      whereas the actin cytoskeleton appeared to be normally polarized. The soluble
      hydrolase carboxypeptidase Y and the lipophilic dye FM 4-64 were targeted
      normally to the vacuole in arp2-1 cells. Thus, Arp2p is required for
      internalization but does not play a major role in later steps of endocytosis.
      Synthetic lethality was demonstrated between arp2-1 and the endocytic mutant end3
      1, suggesting participation of Arp2p and End3p in the same process. Finally, no
      evidence for a major defect in secretion was apparent; invertase secretion and
      delivery of uracil permease to the plasma membrane were unaffected in arp2-1
      cells.

PMID- 9243514
TI  - Second-messenger regulation of receptor association with clathrin-coated pits: a
      novel and selective mechanism in the control of CD4 endocytosis.
AB  - CD4, a member of the immunoglobulin superfamily, is not only expressed in T4
      helper lymphocytes but also in myeloid cells. Receptor-mediated endocytosis plays
      a crucial role in the regulation of surface expression of adhesion molecules such
      as CD4. In T lymphocytes p56lck, a CD4-associated tyrosine kinase, prevents CD4
      internalization, but in myeloid cells p56lck is not expressed and CD4 is
      constitutively internalized. In this study, we have investigated the role of
      cyclic AMP (cAMP) in the regulation of CD4 endocytosis in the myeloid cell line
      HL-60. Elevations of cellular cAMP were elicited by 1) cholera toxin, 2)
      pertussis toxin, 3) forskolin and IBMX, 4) NaF, or 5) the physiological receptor
      agonist prostaglandin E1. All five interventions led to an inhibition of CD4
      internalization. Increased cAMP levels did not inhibit endocytosis per se,
      because internalization of insulin receptors and transferrin receptors and fluid
      phase endocytosis were either unchanged or slightly enhanced. The mechanism of
      cAMP inhibition was further analyzed at the ultrastructural level. CD4
      internalization, followed either by quantitative electron microscopy
      autoradiography or by immunogold labeling, showed a rapid and temperature
      dependent association of CD4 with clathrin-coated pits in control cells. This
      association was markedly inhibited in cells with elevated cAMP levels. Thus these
      findings suggest a second-messenger regulation of CD4 internalization through an
      inhibition of CD4 association with clathrin-coated pits in p56lck-negative cells.

PMID- 9243515
TI  - Clonidine administration increases neuropeptide Y immunoreactivity and
      neuropeptide Y mRNA in the rat cerebral cortex neurons.
AB  - The effect of alpha 2 adrenoceptor stimulation on neuropeptide Y (NPY) and
      NPYmRNA expression was studied in the rat cerebral cortex. For receptor
      stimulation clonidine was used in a dose of 50 micrograms/kg s.c., 3 times at
      every 8 h; brains were studied 30-40 min after the last dose using
      radioimmunoassay (RIA), immunocytochemistry and in situ hybridization methods.
      The RIA of NPY did not show any significant changes in the NPY immunoreactivity
      (IR) level in the whole cortex, whereas the immunohistochemical analysis
      demonstrated an increase in the number of NPY-IR neurons in ventral cortical
      regions, especially in external cortical layers. In situ hybridization
      histochemistry of NPYmRNA also performed in ventral cortical sections showed that
      clonidine increased NPY synthesis in some cortical neurons. The obtained results
      indicate that the alpha 2 adrenoceptor stimulation by clonidine increases the NPY
      content and synthesis in rat cortical neurons.

PMID- 9243516
TI  - PreproVIP-derived peptides in the human female genital tract: expression and
      biological function.
AB  - The aim of the study was to elucidate the localization, distribution,
      colocalization and biological effect of preproVIP-derived peptides in the human
      female genital tract. Radioimmunoassays applying antisera against the five
      functional domains of the VIP precursor in combination with immunohistochemistry
      were used. The effect of preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170
      on genital smooth muscle activity in the Fallopian tube was investigated in vitro
      and compared to that of VIP. All the preproVIP-derived peptides were expressed
      throughout the genital tract in neuronal elements closely related to the
      epithelial lining, perivascular tissue and non-vascular smooth muscle.
      Colocalization of the peptides was evidenced by double immunostaining. In
      contrast to VIP, preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 did not
      cause a significant inhibition of smooth muscle activity. The findings indicate
      that tissue-specific differences in post-translational processing of preproVIP
      exist in the female genital tract.

PMID- 9243517
TI  - Influence of epidermal growth factor and gastrin on the cell proliferation of
      human meningiomas versus astrocytic tumors maintained as ex vivo tissue cultures.
AB  - The hormone sensitivity of a tumor is traditionally based on the presence of
      steroid receptors. Other factors should be taken into consideration. Here, we
      studied the influence of 10 nM epidermal growth factor (EGF) or gastrin on the
      proliferation of human ex vivo tumor cultures by means of [3H]thymidine
      autoradiography. The immunohistochemical EGF-receptor expression was also
      quantified by means of computer-assisted microscopy. The results demonstrated
      that the proliferation of 6/11 astrocytic tumors and 3/16 meningiomas was
      sensitive to at least one factor tested, i.e. EGF or gastrin (P < 0.01), and 5 of
      these 9 'hormone-sensitive' tumors were sensitive to both factors. The
      immunohistochemical labeling index for the EGF receptor was higher than 80% in
      15/16 meningiomas, but only in 6/11 gliomas (P < 0.01). These results suggest
      that EGF and gastrin are important for astrocytic tumor proliferation and
      significantly (P < 0.01) less important for meningiomas. Thus, astrocytic tumors
      may be steroid insensitive in term of cell growth, but are certainly not hormone
      insensitive.

PMID- 9243518
TI  - Coexistence of NADPH-diaphorase with tyrosine hydroxylase in hypothalamic
      magnocellular neurons of the rat.
AB  - The presence and distribution of NADPH-diaphorase (ND) neurons as well as
      tyrosine hydroxylase-immunoreactive (TH) neurons in the hypothalamus are well
      established. Previous studies have shown the coexistence of ND with neuroactive
      substances such as calbindin, somatostatin, vasopressin and oxytocin in neurons
      of this region of the brain. As the topographical patterns of distribution of ND
      and TH coincide in many cases, the aim of this study was to determine the
      possible coexistence of both substances in the main hypothalamic magnocellular
      nuclei of the albino rat. Histochemical-immunocytochemical double labelling was
      employed on the same sections as well as a morphometric study. NADPH-diaphorase
      and tyrosine hydroxylase neurons were observed in all the nuclei under study
      (supraoptic, paraventricular and accessory nuclei), although most neurons showing
      the coexistence of both substances were mainly located in the supraoptic nucleus,
      isolated neurons with double labelling being found in the magnocellular parts of
      the paraventricular nucleus and in some of the accessory nuclei. Although both
      substances have previously been shown to be modified in hypothalamic neurons
      after osmotic stimuli, the range of functions of ND in the CNS is only beginning
      to be understood. Further studies are needed to elucidate the functional role
      that ND/TH neurons play in the nervous system.

PMID- 9243519
TI  - Neostriatal neurons of rats can be influenced by cholecystokinin-A receptor
      agonists.
AB  - The present study investigated the effects of agonists of the neuropeptide
      cholecystokinin (CCK) on neostriatal neurons in order to confirm the existence of
      CCK-A receptors in the rat caudate-putamen. Single unit activity was recorded in
      rats anaesthetized with urethane. The CCK-A receptor agonists A-71378 (desamino
      Tyr(SO3H)-Nle-Gly-Trp-Nle-(N-methyl)Asp-Phe-NH2), and A-71623 (Boc-Trp
      Lys(epsilon-N-2-methylphenylamino-carbonyl)-Asp-(N-methyl )Phe-NH2, as well as
      the CCK-B receptor agonist Suc-CCK-4 (Suc-Trp-(N-methyl)Nle-Asp-Phe-NH2) were
      iontophoretically administered with multibarrel capillaries. About one-third of
      the neurons responded to the CCK-A receptor agonists. Excitatory effects
      predominated. The CCK-B receptor agonist also induced mainly increases in the
      neuronal firing. Several neurons were affected by both types of agonists. The
      results suggest that in the rat neostriatum not only CCK-B receptors, but also
      CCK-A receptors seem to mediate the effects of cholecystokinin.

PMID- 9243520
TI  - Changes in rat melanin-concentrating hormone and dynorphin messenger ribonucleic
      acids induced by food deprivation.
AB  - Melanin-concentrating hormone (MCH) and dynorphin genes are expressed in two
      discrete neuron populations of the rat lateral hypothalamus. Their roles remain
      hypothetical in mammals. In order to analyse changes in MCH and dynorphin gene
      expression, a multiplex competitive semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) was developed to assay their mRNAs. This
      technique was used to examine MCH and dynorphin mRNA content in 24-h and 48-h
      food-deprived rats compared to controls. A two-fold induction of dynorphin mRNA
      by 24 h, followed by a sharp decrease at 48 h were observed. A moderate increase
      in MCH mRNA content was noticed by 24 h; 48 h of fasting restored the control
      levels.

PMID- 9243521
TI  - Substance P(6-11) and natural tachykinins interact with septide-sensitive
      tachykinin receptors coupled to a phospholipase C in the rat urinary bladder.
AB  - The rat urinary bladder possesses NK1, NK2 (but not NK3) and 'septide-sensitive'
      tachykinin receptors coupled to a phospholipase C. The present study performed
      with SR48968 (10(-6) M) to avoid any interaction of the tested peptides with NK2
      receptors, indicates that substance P(6-11) (with a high potency), neurokinin A,
      neurokinin B and to a lesser extent neuropeptide K (with a lower potency)
      stimulate [3H]-inositol monophosphate ([3H]-IP1) formation in this tissue by
      acting on the 'septide-sensitive' tachykinin receptors. Substance P(6-11) had
      little affinity for NK1 binding sites and stimulated [3H]-IP1 formation with an
      EC50 value and a maximal amplitude similar to those of septide. As previously
      observed with septide, this maximal response of substance P(6-11) (insensitive to
      10(-6) M SR48968) which was about three-fold that of substance P, was blocked by
      the NK1 receptor antagonist RP67580 and prevented by [Pro9]substance P (NK1
      receptor agonist). Similarly, substance P and several substance P C-terminal
      fragments prevented the substance P(6-11)-evoked response. In addition,
      neurokinin A, neuropeptide K and neurokinin B induced SR48968-resistant responses
      which exhibited a maximal amplitude similar to that of substance P (6-11) and
      were blocked by RP67580 and totally or partially (neuropeptide K) prevented by
      [Pro9]substance P.

PMID- 9243523
TI  - Endogenous neuropeptides in patients with acute traumatic head injury. II:
      Changes in the levels of cerebrospinal fluid substance P, serotonin and lipid
      peroxidation products in patients with head trauma.
AB  - The cerebrospinal fluid (CSF) levels of substance P (SP), serotonin (5-HT) and
      lipid peroxidation (LPx) products were measured in patients with traumatic head
      injury and then compared to the levels obtained from control subjects. CSF
      samples were collected from 45 patients (31 male, 14 female, aged 19.2 +/- 17.79)
      within 24 h of the head trauma and the control CSF samples were obtained from 25
      healthy subjects (23 male, 2 female, aged 51.44 +/- 17.6 years) having minor
      surgical operations under spinal anaesthesia. CSF SP and 5-HT levels in patients
      with head trauma were significantly lower than the levels in controls (P < 0.005,
      P < 0.001, respectively). On the other hand, the CSF Lpx products were
      significantly increased in patients with head trauma (P < 0.001). No significant
      correlation was found between the CSF changes and the admission Glasgow Coma
      Scale scores of the patients. This study constitutes the second part of our work
      on endogenous neuropeptides in patients with traumatic head injury and it
      emphasizes the role of SP, 5-HT and lipid peroxidation as additional endogenous
      factors in traumatic head injuries.

PMID- 9243522
TI  - Effects of repeated cocaine administration on the thyrotropin-releasing hormone
      level and receptors in the rat brain.
AB  - The effects of single and repeated administration of cocaine on the thyrotropin
      releasing hormone (TRH) level and receptors in discrete rat brain structures were
      evaluated. Male Wistar rats received saline or cocaine (15 mg/kg i.p., once an
      hour within 3 h, for 8 days). The animals were killed by decapitation at 45 min
      and 72 h (chronic group only) after the last injection. A radioimmunoassay (RIA)
      study showed that a single dose of cocaine increased the TRH level in the
      striatum by 68%, but had no significant effect on the peptide content in the
      nucleus accumbens, hippocampus, amygdala, septum, hypothalamus, frontal and
      prefrontal cortex at 45 min after the drug injection. Repeated administration of
      cocaine increased the TRH level in the striatum by 89% at 45 min, and in the
      hippocampus by 26% at 72 h after the last dose. No changes in the TRH level were
      found in other brain structures. In vitro cocaine (10(-6)-10(-4) M) inhibited the
      K(+)-stimulated release in a concentration-dependent manner, but had no effect on
      the basal release of TRH from the striatum and nucleus accumbens of naive rats.
      Acute cocaine decreased the Bmax of TRH receptors in the striatum, but had no
      effect on the density and affinity of TRH receptors in other brain regions.
      Repeated administration of cocaine evoked a long-lasting decrease in the Bmax of
      TRH receptors in the striatum (by c. 30%), whereas an increase in that parameter
      was observed in the frontal cortex. The Bmax and affinity of TRH receptors
      following repeated cocaine remained unchanged in the nucleus accumbens. The
      results obtained indicate that cocaine affects the TRH system mainly in the
      striatum, and to a lesser extent in the nucleus accumbens, cortex and
      hippocampus. Furthermore, the above changes do not resemble those induced by
      amphetamine, which points to certain differences in adaptation of the TRH
      neuronal system to these psychostimulants. On the other hand, the increase in the
      hippocampal TRH level during both chronic cocaine and morphine withdrawal is a
      common feature of the mechanism of dependence on these drugs.

PMID- 9243525
TI  - Isolation and identification of intact chromogranin A and two N-terminal
      processing products, vasostatin I and II, from bovine adrenal medulla chromaffin
      granules by chromatographic and mass spectrometric methods.
AB  - Chromogranin A (CGA) is the most abundant protein of the bovine adrenal medulla
      and plays an important role as precursor protein of several peptides that act as
      modulators for endocrine cell secretory activity. Furthermore, it is presumed to
      play a role in the targeting of peptide hormones and neurotransmitters to
      granules of the regulated pathway. However, its complete primary structure and
      proteolytic processing have not yet been identified. This study describes a rapid
      and efficient procedure for the high yield isolation of bovine CGA and its N
      terminal processing products, vasostatin I and II. Using the lysate from bovine
      adrenal medulla chromaffin granules, the soluble proteins were purified by three
      consecutive HPLC steps, thereby avoiding the use of buffer solutions. The protein
      fractions were isolated and characterized by SDS-PAGE and Western blot analysis
      as well as by mass spectrometry. In the latter analysis, the efficiency of matrix
      assisted laser desorption ionization-mass spectrometry (MALDI-MS) was
      demonstrated, enabling the unequivocal and sensitive characterization of proteins
      from crude mixtures. Sufficient amounts of pure protein were obtained by the
      present procedure to form the basis for detailed structural studies by
      spectroscopic methods and X-ray crystallography.

PMID- 9243524
TI  - Tachykinin NK1 and NK2 receptors mediate non-adrenergic non-cholinergic
      excitatory neuromuscular transmission in the human ileum.
AB  - Tachykinin NK1 and NK2 receptor selective antagonists and agonists were used to
      study excitatory non-adrenergic non-cholinergic (NANC) transmission in circular
      muscle strips from human ileum by the sucrose-gap method. In the presence of
      atropine (1 microM), guanethidine (3 microM), indomethacin (3 microM), apamin
      (0.1 microM), and N omega-nitro-L-arginine (L-NOARG, 30 microM), electrical field
      simulation (EFS) produced a NANC inhibitory junction potential (i.j.p.) followed
      by NANC excitatory junction potential (e.j.p.) with superimposed action
      potentials and contraction of the circular muscle of human ileum. The selective
      tachykinin NK1 receptor antagonist, GR 82334 (0.1-3 microM) produced a
      concentration-dependent inhibition of the EFS-evoked NANC e.j.p. (IC50 = 0.21
      microM) and contraction (IC50 = 0.21 microM). The selective tachykinin NK2
      receptor antagonist, MEN 10627 (0.01-1 microM), likewise produced a concentration
      dependent inhibition of the EFS-evoked NANC e.j.p. (IC50 = 0.07 microM) and
      contraction (IC50 = 0.03 microM). Either antagonist was more effective in
      inhibiting the mechanical than the electrical response to EFS. Neither GR 82334
      nor MEN 10627 had any effect on the apamin- and L-NOARG-resistant NANC i.j.p.
      Activation of the NK1 or NK2 receptors by the selective receptor agonists,
      [Sar9]substance P (SP) sulfone and [beta Ala8]neurokinin A (NKA) (4-10),
      respectively (0.3 microM for 20 s each), produced depolarization with
      superimposed action potentials and contractions. GR 82334 selectively inhibited
      the responses to [Sar9]]SP sulfone, without affecting the responses to [beta
      Ala8]NKA (4-10). MEN 10627 inhibited the responses to [beta Ala8]NKA (4-10),
      without affecting the responses to [Sar9]SP sulfone. We conclude that both
      tachykinin NK1 and NK2 receptors co-operate in producing NANC excitation and
      contraction of the circular muscle in human ileum.

PMID- 9243526
TI  - Role of different neurotransmitter systems in the cholecystokinin octapeptide
      induced anxiogenic response in rats.
AB  - The possible involvement of different neurotransmitter systems in the anxiogenic
      action of cholecystokinin octapeptide sulphate ester (CCK-8) was investigated in
      rats. Intracerebroventricularly (i.c.v.) administered CCK-8 induced an anxiogenic
      response in an elevated plus-maze test. Pretreatment with dopaminergic,
      muscarinergic acetylcholine receptor blockers and an opiate receptor antagonist
      blocked the anxiogenic response to CCK-8. The alpha and beta adrenoreceptor, the
      GABA receptor and the 5-hydroxytryptamine (5-HT) receptor blockers were not able
      to modulate the 'anxiogenic-like' effect of CCK-8. The results suggest that the
      anxiogenic effects of CCK-8 are mediated via different neurotransmitters and the
      anxiogenic action can be prevented by receptor blockers to these transmitters.

PMID- 9243527
TI  - CI 988, an antagonist of the cholecystokinin-B receptor, potentiates endogenous
      opioid-mediated antinociception at spinal level.
AB  - The effects of RB 101 {N-[(R, S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl
      dithio]-1-oxo-propyl]-L-phenylalanine benzyl ester}, a complete inhibitor of
      enkephalin-degrading enzymes and CI 988, a selective antagonist of the
      cholecystokinin (CCK)-B receptors, on the flexor reflex in decerebrate,
      spinalized, unanaesthetized rats were assessed. Intravenous RB 101 induced a dose
      dependent depression of the flexor reflex with a threshold dose of 20 mg/kg and
      an ED50 of 25.3 mg/kg. Subcutaneous CI 988 at 1 mg/kg, which by itself did not
      influence the flexor reflex, strongly enhanced the reflex depressive effect of RB
      101. The dose-response curve for RB 101 was shifted to the left and the duration
      of reflex depression was significantly prolonged. The results confirmed and
      extended previous behavioural data indicating that blockade of CCK-B receptors
      potentiated antinociception elicited by endogenous opioids protected from
      enzymatic degradation. Furthermore, the spinal cord is an important site of
      interaction between the endogenous opioid and CCK systems.

PMID- 9243528
TI  - Emotional disturbances and their interaction with neuropsychological deficits.
AB  - The interaction and relationships between neuropsychological tests (which are
      principally oriented to intellectual and cognitive abilities) and tests of
      personality and emotional status are complex, but nevertheless important in the
      clinical assessment of brain-damaged persons. Are indications of emotional
      disturbances to be expected as a direct consequence of brain damage? If so, how
      can the indications of emotional disturbances be differentiated from results
      obtained with psychiatrically disturbed (non-brain-damaged) subjects? Some
      authors have presumed that emotional disturbances, such as depression, acute
      anxiety, etc., in their own right cause impaired performances on
      neuropsychological tests, whereas other authors have proposed that brain damage
      predisposes the individual to demonstrate evidence of emotional disturbances. If
      emotional disturbances cause impairment on neuropsychological tests, why is it
      that so many emotionally disturbed persons without brain damage tend to perform
      normally on neuropsychological tests? This review of relevant publications
      considers (1) different general approaches to these questions and their
      implications for neuropsychology, (2) evidence of differential sensitivity to
      brain damage of neuropsychological and emotional instruments, (3) the sensitivity
      and specificity of self-assessments and complaints of head-injured subjects, (4)
      MMPI findings among head-injured subjects and in interaction with
      neuropsychological measurements, and (5) principles and guidelines that may be of
      value in clinical application of findings reported in the literature.

PMID- 9243529
TI  - Cognitive rehabilitation of chronic alcohol abusers.
AB  - The current literature suggests that individuals who chronically abuse alcohol
      exhibit a wide variety of cognitive deficits resulting from cerebral dysfunction
      that is either directly or indirectly related to their alcohol consumption
      history. Cognitive deficits have been hypothesized as having implications for
      standard alcohol treatment efficacy as they may directly affect cognitively
      impaired individuals' abilities to utilize various treatment modalities. Although
      evidence is accumulating that suggests this is actually the case, the majority of
      alcohol treatment programs neither directly consider the impact cognitive
      deficits have on treatment efficacy nor do they employ cognitive rehabilitation
      treatment strategies to remediate identified cognitive deficits. Few studies
      exist that investigate the remediability of neurobehavioral deficits or the
      efficacy of integrating cognitive rehabilitation strategies into more traditional
      treatment programs. Empirical investigations conducted to date indicate that some
      cognitive deficiencies secondary to alcoholism are amenable to cognitive
      rehabilitation and this remediation is generalizable. Rigorous well-controlled
      treatment outcome investigations are needed in order to determine the efficacy of
      cognitive rehabilitation techniques in naturalistic settings using ecological
      outcome measures. Also, emphasis should be placed on integrating cognitive
      rehabilitation techniques with proven efficacy into traditional alcoholism
      treatment programs.

PMID- 9243531
TI  - New statistical methods for substance use prevention research.

PMID- 9243530
TI  - Neuropsychological aspects of facial asymmetry during emotional expression: a
      review of the normal adult literature.
AB  - This review focuses on facial asymmetries during emotional expression. Facial
      asymmetry is defined as the expression intensity or muscular involvement on one
      side of the face ("hemiface") relative to the other side and has been used as a
      behavioral index of hemispheric specialization for facial emotional expression.
      This paper presents a history of the neuropsychological study of facial
      asymmetry, originating with Darwin. Both quantitative and qualitative aspects of
      asymmetry are addressed. Next, neuroanatomical bases for facial expression are
      elucidated, separately for posed/voluntary and spontaneous/involuntary
      elicitation conditions. This is followed by a comprehensive review of 49
      experiments of facial asymmetry in the adult literature, oriented around
      emotional valence (pleasantness/unpleasantness), elicitation condition, facial
      part, social display rules, and demographic factors. Results of this review
      indicate that the left hemiface is more involved than the right hemiface in the
      expression of facial emotion. From a neuropsychological perspective, these
      findings implicate the right cerebral hemisphere as dominant for the facial
      expression of emotion. In spite of the compelling evidence for right-hemispheric
      specialization, some data point to the possibility of differential hemispheric
      involvement as a function of emotional valence.

PMID- 9243532
TI  - Analysis with missing data in drug prevention research.
AB  - Missing data problems have been a thorn in the side of prevention researchers for
      years. Although some solutions for these problems have been available in the
      statistical literature, these solutions have not found their way into mainstream
      prevention research. This chapter is meant to serve as an introduction to the
      systematic application of the missing data analysis solutions presented recently
      by Little and Rubin (1987) and others. The chapter does not describe a complete
      strategy, but it is relevant for (1) missing data analysis with continuous (but
      not categorical) data, (2) data that are reasonably normally distributed, and (3)
      solutions for missing data problems for analyses related to the general linear
      model in particular, analyses that use (or can use) a covariance matrix as input.
      The examples in the chapter come from drug prevention research. The chapter
      discusses (1) the problem of wanting to ask respondents more questions than most
      individuals can answer; (2) the problem of attrition and some solutions; and (3)
      the problem of special measurement procedures that are too expensive or time
      consuming to obtain for all subjects. The authors end with several conclusions:
      Whenever possible, researchers should use the Expectation-Maximization (EM)
      algorithm (or other maximum likelihood procedure, including the multiple-group
      structural equation-modeling procedure or, where appropriate, multiple
      imputation, for analyses involving missing data [the chapter provides concrete
      examples]); If researchers must use other analyses, they should keep in mind that
      these others produce biased results and should not be relied upon for final
      analyses; When data are missing, the appropriate missing data analysis procedures
      do not generate something out of nothing but do make the most out of the data
      available; When data are missing, researchers should work hard (especially when
      planning a study) to find the cause of missingness and include the cause in the
      analysis models; and Researchers should sample the cases originally missing
      (whenever possible) and adjust EM algorithm parameter estimates accordingly.

PMID- 9243533
TI  - Latent class analysis of substance abuse patterns.
AB  - This chapter discusses use of latent class analysis (LCA) as a tool for
      identifying substance use patterns in cross-sectional data. LCA serves as an
      exploratory and data reduction tool that helps clarify the nature of substance
      use and may provide insight concerning effective prevention strategies. LCA is
      well suited to categorical data such as typically are collected in substance use
      research. Use of LCA can be divided into three steps: (1) model comparison and
      selection, (2) assignment of cases to latent classes, and (3) interpretation of
      the latent classes. Quantitative indices of model fit may assist model comparison
      and selection. Latent classes can be interpreted by examining probabilities of
      substance use in each latent class and by examining differences on exogenous
      variables. Limitations, extensions, and software for LCA are discussed. An
      example illustrates use of LCA with actual data collected from a current
      substance abuse prevention study.

PMID- 9243534
TI  - Latent transition analysis and how it can address prevention research questions.
AB  - The objective of this chapter is to introduce latent transition analysis (LTA) to
      the substance use prevention research community. LTA is a new methodological
      technique for testing stage-sequential models, such as models of substance use
      onset. LTA estimates several different sets of parameters. One of these sets is
      the transition probability matrix, which contains information about the
      probability of movement between stages in the model. LTA can be used to evaluate
      the effectiveness of prevention intervention programs by comparing the transition
      probability matrices of the program and control groups. If the prevention program
      is successful, the transition probability matrices will indicate that the
      probability of moving to a more advanced stage of drug use is lower for the
      program participants than for the control group. An advantage of taking a stage
      sequential approach is that examining the transition probability matrix reveals
      how effective a program is for individuals entering the program with different
      levels and types of substance use experience. In this chapter, LTA is used to
      evaluate a variety of models of the early onset process separately for Anglo,
      Latino, and Asian-American adolescents, measured in seventh grade and again in
      eighth grade. Although somewhat different models are found to fit the three
      ethnic groups best, the differences likely are due to differences in the overall
      amount of substance use experience. Based on these results, it is suggested that,
      to be most effective, prevention programs should take place earlier for Anglos
      and Latinos, and later, followed by boosters, for Asian Americans.

PMID- 9243535
TI  - Incorporating trend data to aid in the causal interpretation of individual-level
      correlations among variables: examples focusing on the recent decline in
      marijuana use.
AB  - Given the close correspondence of several trends beginning in 1979, it is
      tempting to conclude that increases in perceived risk and disapproval led to the
      decline in actual use of marijuana. In this chapter, two alternative
      interpretations are considered, reflecting different hypotheses about individual
      level causal processes: (1) changes in use led to the changes in attitudes, or
      (2) changes in some other factor(s) (e.g., increased "conventionality") caused
      both changes in use and changes in attitudes. This chapter documents a series of
      analyses designed to untangle such issues by incorporating trend data along with
      individual-level, cross-sectional relationships. One analysis strategy shows that
      controlling attitudes could "account for" the time trend in marijuana use,
      whereas the reverse is not true. The second analysis strategy examines how time
      trends in marijuana use are affected by multivariate controls for attitudes, as
      well as other individual characteristics, and shows that only the attitude
      measures can "explain" the time trend in marijuana use. Although these analyses
      are viewed as helping to explain the recent secular trend downward in marijuana
      use, as well as the still more recent decline in cocaine use, their most
      important contribution to prevention intervention research may be that they
      support a very basic generalization about individual-level causal processes:
      individual attitudes about specific drugs affect individuals use of those drugs.

PMID- 9243536
TI  - Multilevel models for hierarchically nested data: potential applications in
      substance abuse prevention research.
AB  - This chapter reports on an application of a multilevel analysis. A multilevel
      analysis is a data analysis that uses variables that are measured at different
      levels of the hierarchy. A hierarchy can have many levels, such as student level,
      class level, school level, and State or country level, where students are nested
      within classes, classes are nested within schools or school districts, and school
      districts can be nested within towns, States, or countries. As soon as one pays
      attention, hierarchies are present in all data. In large-scale prevention
      research, researchers usually have information about two or more levels involved,
      for instance, variables describing individuals (such as achievement, drug use,
      gender, and measures of socioeconomic status or home environment); variables
      describing schools (such as school environment, urban versus rural, and type of
      treatment administered); and perhaps variables describing districts, States, or
      countries. It is well known that the analysis of variables (i.e., measures at
      different levels of the hierarchy) on any of these levels separately can be
      misleading, as will be shown in this chapter. It is more satisfactory to
      construct a model and technique that simultaneously take information on all
      levels into account. This chapter introduces such a multilevel model for
      hierarchically nested data by evaluating the effect of a drug prevention program,
      Normative Education (NORM), wherein data are collected on students nested within
      schools. The model is a linear regression model. The difference between this
      model and the traditional linear regression model is that it takes the intraclass
      correlation into account and treats variables measured at different levels of the
      hierarchy in a more appropriate way.

PMID- 9243537
TI  - Seven ways to increase power without increasing N.
AB  - Many readers of this monograph may wonder why a chapter on statistical power was
      included. After all, by now the issue of statistical power is in many respects
      mundane. Everyone knows that statistical power is a central research
      consideration, and certainly most National Institute on Drug Abuse grantees or
      prospective grantees understand the importance of including a power analysis in
      research proposals. However, there is ample evidence that, in practice,
      prevention researchers are not paying sufficient attention to statistical power.
      If they were, the findings observed by Hansen (1992) in a recent review of the
      prevention literature would not have emerged. Hansen (1992) examined statistical
      power based on 46 cohorts followed longitudinally, using nonparametric
      assumptions given the subjects' age at posttest and the numbers of subjects.
      Results of this analysis indicated that, in order for a study to attain 80
      percent power for detecting differences between treatment and control groups, the
      difference between groups at posttest would need to be at least 8 percent (in the
      best studies) and as much as 16 percent (in the weakest studies). In order for a
      study to attain 80-percent power for detecting group differences in pre-post
      change, 22 of the 46 cohorts would have needed relative pre-post reductions of
      greater than 100 percent. Thirty-three of the 46 cohorts had less than 50-percent
      power to detect a 50-percent relative reduction in substance use. These results
      are consistent with other review findings (e.g., Lipsey 1990) that have shown a
      similar lack of power in a broad range of research topics. Thus, it seems that,
      although researchers are aware of the importance of statistical power
      (particularly of the necessity for calculating it when proposing research), they
      somehow are failing to end up with adequate power in their completed studies.
      This chapter argues that the failure of many prevention studies to maintain
      adequate statistical power is due to an overemphasis on sample size (N) as the
      only, or even the best, way to increase statistical power. It is easy to see how
      this overemphasis has come about. Sample size is easy to manipulate, has the
      advantage of being related to power in a straight-forward way, and usually is
      under the direct control of the researcher, except for limitations imposed by
      finances or subject availability. Another option for increasing power is to
      increase the alpha used for hypothesis-testing but, as very few researchers
      seriously consider significance levels much larger than the traditional .05, this
      strategy seldom is used. Of course, sample size is important, and the authors of
      this chapter are not recommending that researchers cease choosing sample sizes
      carefully. Rather, they argue that researchers should not confine themselves to
      increasing N to enhance power. It is important to take additional measures to
      maintain and improve power over and above making sure the initial sample size is
      sufficient. The authors recommend two general strategies. One strategy involves
      attempting to maintain the effective initial sample size so that power is not
      lost needlessly. The other strategy is to take measures to maximize the third
      factor that determines statistical power: effect size.

PMID- 9243538
TI  - Designing and analyzing studies of onset, cessation, and relapse: using survival
      analysis in drug abuse prevention research.
AB  - Many questions arising in drug abuse prevention and intervention studies focus on
      whether and, if so, when events occur. When do adolescents start using drugs?
      Does participation in a drug prevention program at school decrease the risk that
      high school students will initiate drug use? Does failure to participate in a
      relapse prevention program at a community health center increase the risk that
      newly abstinent ex-abusers will start using drugs again? Research questions about
      event occurrence present unique design and analytic difficulties. The fundamental
      problem is how to handle censored observations, observations of those people who
      do not experience the target event during data collection. The methods of
      survival analysis overcome these difficulties and allow prevention researchers to
      describe patterns of occurrence, compare these patterns among groups, and build
      statistical models of the risk of occurrence over time. In this chapter, the
      authors present a nonmathematical introduction to survival analysis for drug
      abuse prevention researchers. After developing the basic concepts, they focus on
      two topics-study design and data analysis-and identify for each the key issues
      researchers face and provide guidelines for making informed decisions about them.
      In the process, the authors review how prevention researchers have used the
      methods to date and point towards new directions for the application of these
      methods.

PMID- 9243540
TI  - Use and misuse of repeated measures designs.
AB  - Repeated measures designs should be used more frequently in prevention
      intervention research. They are the design of choice when one or more
      measurements have been taken at baseline followed by one or more measurements
      after prevention intervention. They may be used to ask questions about
      differences on measurements at different points in time and between measures made
      on the same scale. In this presentation, prevention intervention researchers are
      provided with a step-by-step discussion of this design, examples of prevention
      intervention repeated measures designs, and a discussion of the misuses of this
      design.

PMID- 9243539
TI  - Time series models of individual substance abusers.
AB  - Time series analysis is a statistical procedure appropriate for repeated
      observations on a single subject or unit. The goal of the analysis may be to
      determine the nature of the process that describes an observed behavior or to
      evaluate the effects of a treatment or intervention. Model identification
      involves specifying which of several alternative Autoregressive Integrated Moving
      Average (ARIMA) models best describes the series and may be used to investigate
      basic processes. This is illustrated by an example involving selecting the model
      of nicotine regulation that best represents smokers. Intervention analysis
      involves determining if there are any changes in level or direction for the
      series as a result of the intervention. Two types of applications have potential
      for the substance abuse area: (1) evaluation of the effects of an intervention on
      a single individual, and (2) evaluation of organizational-level changes (i.e.,
      program evaluation). This is illustrated by an example that examines the effect
      of relaxation therapy on blood pressure. Pooled time series procedures are
      employed to combine the data from several different individuals or units, either
      by cross-sectional analysis or meta-analysis. In addition, several other issues
      are discussed that are critical to performing a time series analysis: selection
      of an appropriate computer program, alternative procedures for handling missing
      data, procedures for multiple observations at each occasion, and corrections for
      seasonal data.

PMID- 9243541
TI  - Meta-analytical issues for prevention intervention research.
AB  - Lack of systematic methods for comparing diversified programs has limited the use
      of research results. Drug prevention intervention research has a history of mixed
      or marginal results, a situation that leads to the supposition that programs do
      not work. Meta-analytical methods have successfully resolved problems of
      conflicting results and are a cost-effective method for building a knowledge
      base. Using both qualitative and quantitative methods, meta-analysis applies all
      of the scientific rigor of primary research to the integration of this research.
      Quantitative synthesis is accomplished by computing an effect size, which, unlike
      significance test, allows comparisons across studies having varied sample sizes.
      One advantage for drug prevention intervention research, which seldom shows
      statistically significant results, is the powerful findings produced when small
      positive effect sizes are consistent across many studies. Generalizability is
      possible through meta-analytic aggregation, as a large body of studies contain
      all the exigencies of real-world research. Troublesome areas that can distort
      conclusions are presented to alert readers of literature reviews so they are able
      to interpret meta-analytic reviews accurately. Specific problematic issues are
      introduced, such as preexisting differences, combining efficacy and
      implementation studies, and the use of the weighted effect size with a group of
      studies that has a large range in sample sizes. Meta-analytic procedures are
      illustrated by comparing the results of 114 experimental and quasi-experimental
      school-based adolescent drug prevention programs with a selected subset of 56
      higher quality experimentally evaluated programs.

PMID- 9243542
TI  - Dynamic systems-modeling as a means to estimate community-based prevention
      effects.
AB  - The best applications of prevention programming now are believed to be community
      supported strategies, comprehensive in scope, implemented in stages, and
      delivered by public and private agencies and organizations. Despite the flurry of
      program activity, research directed toward comprehensive, community-based
      prevention programming remains a largely uncharted domain. Communities need to
      know what will work-in their specific contexts. The essential question
      communities are asking themselves and consultants is, "Which mix of interventions
      will yield maximum reduction in alcohol and other drug (AOD) abuse in our
      community?" Computer-based dynamic simulation modeling holds promise in helping
      provide an answer to this question. These models are designed to replicate the
      historic patterns and dynamics of target communities with regard to substance
      availability, use, and misuse and then to simulate future patterns and dynamics
      under alternative assumptions and intervention mixes. Researchers can use these
      models to construct structural relationships that reflect alternative theories or
      explanations for important processes. The models afford community planners and
      decision-makers with mechanisms for asking "what if" questions regarding
      alternative intervention mixes and, consequently, for determining which
      politically acceptable mix of feasible interventions will yield the most
      reduction in AOD-related problem behaviors. In this chapter, a model under
      development by the Prevention Research Center of the Pacific Institute for
      Research and Evaluation is described that focuses on alcohol use and misuse in
      communities and allows the testing of a wide range of prevention options.

PMID- 9243543
TI  - Treatment for drug addiction: it won't work if they don't receive it.

PMID- 9243544
TI  - Enhancing retention in clinical trials of psychosocial treatments: practical
      strategies.
AB  - Given the close links between retention and outcome in substance abuse treatment,
      it is important to recognize that treatments are successful to the degree they
      retain patients. This chapter described some practical strategies for improving
      retention in clinical trials of treatment for substance abuse. To summarize: 1.
      Retention can be conceived as an important treatment outcome that reflects good
      fit between patient, therapist, treatment, and setting. Procedures and practices
      that improve the quality of treatment are likely to also improve retention. 2.
      Attending to the problem of retention may help solve the problem. While trials
      are ongoing, investigators should monitor retention closely, attending to and
      addressing variations in retention that might be associated with setting,
      seasonal variations, therapist factors, and research procedure factors. 3. More
      data are needed on effective methods of enhancing retention in different
      treatment settings. It should be noted that the strategies presented here reflect
      common sense and are for the most part drawn from experience with several
      clinical trials. Few of them have been evaluated empirically. However, more data
      on effective retention strategies are likely to have broad clinical and research
      utility. For example, it would be possible to design studies that evaluate an
      adaptation of Higgins' voucher system (this volume) to specifically reinforce
      retention in treatments that have higher rates of attrition, different methods of
      rewarding clinicians with higher rates of retention, and the effect on retention
      of adding babysitting services, to mention but some areas where further research
      would be illuminating.

PMID- 9243545
TI  - From the initial clinic contact to aftercare: a brief review of effective
      strategies for retaining cocaine abusers in treatment.

PMID- 9243546
TI  - Help-seeking by substance abusers: the role of harm reduction and behavioral
      economic approaches to facilitate treatment entry and retention.

PMID- 9243547
TI  - Tailoring interventions to clients: effects on engagement and retention.

PMID- 9243548
TI  - Factors associated with treatment continuation: implications for the treatment of
      drug dependence.

PMID- 9243550
TI  - The role of family and significant others in the engagement and retention of drug
      dependent individuals.

PMID- 9243549
TI  - Stages of change: interactions with treatment compliance and involvement.
AB  - Current perspectives on compliance and involvement in treatment often overlook
      the fact that treatment occurs in the context of a process of change and not vice
      versa. Each individual moves at a unique pace through a series of stages of
      change and in a cyclical fashion over a substantial period of time. Treatment
      personnel and programs should recognize the diversity of stage status in their
      clients and address each one in a manner compatible with the client's current
      stage of change, the tasks needed to move forward in the process of change, and
      an understanding of the course of change. Such considerations should assist the
      therapist in developing strategies to increase the engagement of a wide variety
      of clients, to improve retention of these clients in a realistic course of
      treatment, and to foster participation in stage-appropriate tasks that promote
      successful movement through the stages to sustained, long-term change.

PMID- 9243551
TI  - Establishing and maintaining a therapeutic alliance with substance abuse
      patients: a cognitive therapy approach.

PMID- 9243552
TI  - Back to basics: fundamental cognitive therapy skills for keeping drug-dependent
      individuals in treatment.
AB  - Cognitive therapists who treat drug-dependent patients are likely to lose at
      least 50 percent of their patients to dropout. This chapter has presented a
      cognitive model for conceptualizing missed sessions and dropout, along with
      strategies for reducing the likelihood of missed sessions and dropout. The
      following should serve to highlight these strategies. 1. Therapists are
      encouraged to offer warm, empathetic, collaborative relationships in which drug
      dependent patients can feel accepted, understood, and validated. 2. Therapists
      are encouraged to develop comprehensive, accurate case conceptualizations, with
      attention paid to the potential for missed sessions and dropout. Case
      conceptualizations should ultimately guide cognitive and behavioral techniques.
      3. Therapists are encouraged to structure sessions and elicit feedback regarding
      their patient's thoughts and beliefs about therapy and the therapist. This
      feedback is facilitated by such questions as, "What do you like most about
      therapy?" "What do you like least?" "What has changed in your life as a result of
      therapy?" "How do you view our relationship?" 4. Therapists are encouraged to
      socialize patients in a timely, appropriate manner. 5. Similar to the process of
      socialization, therapists are encouraged to use cognitive and behavioral
      techniques in a timely, appropriate manner. It is unrealistic to think that the
      problems of missed sessions and dropout from drug treatment will ever be fully
      resolved. Nonetheless, the authors believe that the conceptual models and
      fundamental strategies presented in this chapter represent a significant step in
      addressing these problems.

PMID- 9243553
TI  - Establishing a therapeutic alliance with substance abusers.

PMID- 9243554
TI  - Introduction--the validity of self-reported drug use: improving the accuracy of
      survey estimates.
AB  - Measuring levels and patterns of illicit drug use, their correlates, and related
      behaviors requires the use of self-report methods. However, the validity of self
      reported data on sensitive and highly stigmatized behaviors such as drug use has
      been questioned. The goal of this monograph is to review current and cutting-edge
      research on the validity of self-reported drug use and to describe methodological
      advances designed to reduce total error in estimates of drug use and quantify
      sources of nonsampling error. This monograph reviews a number of studies that use
      some presumably more accurate measure of drug use to validate self-reported use.
      In addition, evolving methods to improve a wide variety of procedures used in
      survey designs are explored, including computer-assisted interviewing, predictors
      of response propensity, measurement error models, and improved prevalence
      estimation techniques. Experimental manipulations of various survey conditions
      and situational factors also show promise in improving the validity of drug
      prevalence estimates in self-report surveys.

PMID- 9243555
TI  - The validity of self-reported drug use in survey research: an overview and
      critique of research methods.
AB  - Since illicit drug use is by definition illegal, the tasks of measuring incidence
      and prevalence and charting the course of the epidemic have fallen to survey
      researchers over the past 30 years. Although survey methods have obvious
      advantages over indirect measures such as arrests, seizures, and treatment
      admissions, they are frequently criticized because the rely on valid self
      reporting of sensitive and highly stigmatized behavior. Validation studies
      conducted before the mid-1980s involving known samples of drug users or
      urinalysis techniques suggested that drug use was fairly accurately reported in
      self-report surveys. However, more recent validation studies conducted with
      criminal justice and former treatment clients using improved urinalysis
      techniques and hair analyses demonstrate that self-report methods miss a lot of
      recent drug use. A review of the research literature suggests that neither self
      reports nor bioassays are wholly accurate, and both have inherent problems.
      However, because self-report measures are necessary to understand the complexity
      of causal and correlational attributes of drug abuse, it is necessary to
      determine what can be done to improve valid self-reporting. This chapter examines
      the research literature on validation studies to provide an overview of what is
      known about the accuracy of self-reported drug use.

PMID- 9243556
TI  - The validity of self-reported drug use data: the accuracy of responses on
      confidential self-administered answered sheets.
AB  - Official records offer a relatively inexpensive, nonintrusive strategy for
      checking on the accuracy of self-reported drug use. Responses of a small sample
      (N = 67) of former drug treatment clients interviewed using procedures exactly
      modeled on the National Household Survey on Drug Abuse were compared to their
      clinic records. The accuracy of reports compared to clinic records varied by
      drug, with the percentage of known users reporting their use highest for
      marijuana, followed by cocaine and hallucinogens, and lowest for heroin. Almost
      half of this sample of former treatment clients denied ever receiving drug
      treatment.

PMID- 9243557
TI  - The recanting of earlier reported drug use by young adults.
AB  - One approach to determining the validity of self-reported drug use measures is to
      examine the extent of logically inconsistent responses over time. Because
      lifetime use logically should never decline, the rate of subsequent recanting of
      earlier reported lifetime use provides relevant evidence on validity. In this
      chapter, recanting rates are examined in nationally representative samples of
      high school seniors (18-year-olds) surveyed in the Monitoring the Future study as
      they are followed up on seven occasions through age 32. For the illegal drugs
      examined (marijuana, cocaine, and lysergic acid diethylamide (LSD)), recanting
      rates prove to be quite modest, but for the psychotherapeutic drugs, they were
      more substantial, possibly because of their greater definitional ambiguity. In
      general, there were no large individual differences in recanting rates as a
      function of sex, household composition, community size, or education level.
      Consistent with previous work, minorities (particularly African Americans) had
      somewhat higher rates of recanting on the illegal drugs. So did respondents in
      certain occupations, namely, the military and police/firefighting. In general,
      however, the evidence is quite good for validity of self-reported (by mail)
      lifetime use of the illegal drugs in young adulthood.

PMID- 9243559
TI  - New developments in biological measures of drug prevalence.
AB  - Drug use among different populations such as household members, students, and
      arrestees vary substantially and the accuracy of their self-reports may be
      questionable. The accuracy of prevalence estimates based on self-report data can
      be monitored by chemical drug testing of biological specimens such as urine,
      saliva, sweat, and hair. Each biological specimen is unique and offers a somewhat
      different pattern of information regarding drug use over time. Also, each
      specimen has unique strengths and weaknesses regarding the type of information
      obtained from drug testing. The performance characteristics of the assay
      methodology may also be important. The validation of self-report data by drug
      testing must be performed with careful consideration of the limitations imposed
      by the testing methodology and the biological specimen.

PMID- 9243558
TI  - The reliability and consistency of drug reporting in ethnographic samples.
AB  - Findings are addressed concerning the reliability of reporting on drug dealing
      and drug use. Reports provided in retrospective life history interviews are
      compared with reports gathered and summarized from eight prospective weekly
      interviews. Most subjects reporting involvement in drug dealing during the weekly
      interviews, also reported involvement in this behavior during the life history
      report. There was a tendency for subjects to deny current involvement in drug
      dealing during the life history reports, even though they reported involvement in
      drug dealing in the weekly interviews. Binary indicators derived from life
      history interviews about current drug use were consistent with reports provided
      prospectively. Subjects reported considerably higher use quantities and
      frequencies for substances in the life history reports than they did in the
      weekly interview reports. These results are examined in the context of other
      recent work examining the reliability of retrospective substance involvement
      reports. Implications for ethnographic research on drug use are discussed.

PMID- 9243560
TI  - Comparison of self-reported drug use with quantitative and qualitative urinalysis
      for assessment of drug use in treatment studies.
AB  - The effectiveness of substance abuse treatment programs can be monitored by self
      reported drug use and objectively measured by qualitative and quantitative
      urinalysis. The advantages and disadvantages of each of these three methods of
      assessing drug use are reviewed. Data collected in a clinical trial of a
      behavioral treatment for cocaine abuse are used to evaluate the relationships
      among qualitative and quantitative urinalysis for cocaine metabolite and self
      reported cocaine use. Qualitative and quantitative urine testing showed greater
      rates of drug use than that shown by self-report, though there were significant
      correlations between self-reported use and urine toxicology results.
      Benzoylecgonine concentrations in urine specimens supported the suggestions that
      rates of drug use as determined by qualitative urinalysis are artificially high
      due to carryover and were informative about subjects' patterns of use.

PMID- 9243561
TI  - The forensic application of testing hair for drugs of abuse.
AB  - Hair testing is only used by the Federal Bureau of Investigation (FBI) when other
      information exists that indicates drug use and can remove a person from suspicion
      or associate them with criminal activity. The detection of cocaine in hair has
      been the FBI's first priority in hair testing for drugs of abuse because of its
      prevalence. Several cases when hair testing was used are reported in this
      chapter. Further, analysis of over 100 samples was performed on hair obtained
      from a medical examiner's random autopsy collection. Sixty-five percent of the
      samples tested positive for cocaine or opiates. The results of hair testing for
      drugs of abuse were found to be consistent with autopsy toxicology reports. The
      analysis of hair washes and nails from the autopsy samples suggests external
      contamination of hair with drugs is not widespread.

PMID- 9243562
TI  - Patterns of concordance between hair assays and urinalysis for cocaine:
      longitudinal analysis of probationers in Pinellas County, Florida.
AB  - This chapter reports on a field trial involving the application of hair assays to
      a probation population. The objectives were to evaluate the general reactions of
      probation officers and probationers to the collection of hair samples, to compare
      the outcomes of the hair samples with the outcomes of urinalyses (which the
      probationers undergo routinely), to note and react to differences in the
      prevalence as indicated by the two assay types, and to assess the general
      monitoring potential for hair assays in a correctional setting. In general, hair
      assays showed an increased capability of detecting cocaine exposure when compared
      to urinalysis. The detection of cannabis was, however, problematic for hair. The
      hair assays, using urine as a comparator, appeared to result in several apparent
      false negatives for cannabinoids. There were no false negatives for cocaine, and
      an approximately fourfold increase in the detection rate when compared to urine.
      The collection of hair samples was not difficult and the cooperation of the
      probationers was quite good. Probation officers appear to prefer the use of hair
      specimens to urine specimen collection, and appeared enthusiastic about the
      potential use of hair analysis in their routine monitoring of clients.

PMID- 9243563
TI  - The validity of self-reports of drug use at treatment admission and at followup:
      comparisons with urinalysis and hair assays.
AB  - Studies conducted in the 1970s and early 1980s concluded that people will provide
      valid information about their illicit drug use when research interviews are
      conducted under appropriate conditions. Recent studies of treated and untreated
      populations using improved urinalysis techniques as well as hair analysis
      techniques indicate that the validity of respondents' self-reports of recent drug
      use may be considerably less than previously reported and may differ according to
      a number of factors. Results are presented from a study of clients participating
      in the Washington, DC, Treatment Initiative study who were assessed for drug use
      by interview, urinalysis, and hair analysis. At intake, almost all clients who
      tested positive had reported their use of heroin but fewer clients had reported
      their cocaine use. At posttreatment followup, clients underreported both heroin
      and cocaine use. Findings from treatment outcome studies that fail to validate
      and adjust their estimates of self-reported recent drug use should be interpreted
      with considerable caution.

PMID- 9243564
TI  - The validity of self-reported cocaine use in two high-risk populations.
AB  - Self-reports of drug use are extensively employed in research on drug use and in
      evaluations of drug abuse treatment and human immunodeficiency virus (HIV)
      prevention interventions. The chapter first summarizes recent research addressing
      the validity of drug use self-reports in high-risk populations. The results of
      two self-report validity studies are then compared, one for a sample of patients
      in methadone maintenance and the other for a sample of criminally involved young
      adults. Cocaine use was more accurately reported by the methadone patients; the
      possible reasons for this are explored.

PMID- 9243565
TI  - Assessing drug use in the workplace: a comparison of self-report, urinalysis, and
      hair analysis.
AB  - A random sample of 1,200 employees of a steel plant in the western United States
      was randomly assigned to four different self-report methods of assessing illicit
      drug use: individual interview in the workplace, group-administered questionnaire
      in the workplace, telephone interview, and individual interview off the worksite.
      Urine specimens were collected and analyzed on all 928 subjects participating in
      the study, and hair analysis was conducted on 307 of the subjects. Although self
      reports produced higher prevalence rates than the chemical tests, analyses
      combining the results of the three assessment methods showed that the actual
      prevalence rate was approximately 50 percent higher than the estimate produced by
      self-reports alone. The group-administered questionnaire method produced
      prevalence rates that were roughly half those of the other self-report methods.
      The findings cast doubt on the validity of self-reports as means of estimating
      drug use prevalence and suggest the need for multiple assessment methods.

PMID- 9243566
TI  - Studies of nonresponse and measurement error in the national household survey on
      drug abuse.
AB  - A summary of the results of a series of studies of nonresponse and measurement
      error in the National Household Survey on Drug Abuse (NHSDA) is given in this
      chapter. Two studies not previously reported, the Skip Pattern Experiment and the
      Census Match Study, are the primary focus of the chapter. The Skip Pattern
      Experiment involved a test of a modified NHSDA questionnaire that made extensive
      use of skip patterns in drug use questions. Compared to the standard NHSDA
      method, which avoids skip patterns, the modified questionnaire tended to produce
      lower rates of reported drug use. The Census Match Study involved linking 1990
      NHSDA nonrespondent cases with data from the 1990 Decennial Census. Household and
      individual data for NHSDA nonrespondents were obtained from the Census and used
      to characterize NHSDA nonresponse patterns in detail. A multilevel logistic model
      of response propensity identified the important predictors of nonresponse,
      including characteristics of the sampled person, the selected household, the
      neighborhood, and the interviewer.

PMID- 9243567
TI  - Adaptive sampling in behavioral surveys.
AB  - Studies of populations such as drug users encounter difficulties because the
      members of the populations are rare, hidden, or hard to reach. Conventionally
      designed large-scale surveys detect relatively few members of the populations so
      that estimates of population characteristics have high uncertainty. Ethnographic
      studies, on the other hand, reach suitable numbers of individuals only through
      the use of link-tracing, chain referral, or snowball sampling procedures that
      often leave the investigators unable to make inferences from their sample to the
      hidden population as a whole. In adaptive sampling, the procedure for selecting
      people or other units to be in the sample depends on variables of interest
      observed during the survey, so the design adapts to the population as
      encountered. For example, when self-reported drug use is found among members of
      the sample, sampling effort may be increased in nearby areas. Types of adaptive
      sampling designs include ordinary sequential sampling, adaptive allocation in
      stratified sampling, adaptive cluster sampling, and optimal model-based designs.
      Graph sampling refers to situations with nodes (for example, people) connected by
      edges (such as social links or geographic proximity). An initial sample of nodes
      or edges is selected and edges are subsequently followed to bring other nodes
      into the sample. Graph sampling designs include network sampling, snowball
      sampling, link-tracing, chain referral, and adaptive cluster sampling. A graph
      sampling design is adaptive if the decision to include linked nodes depends on
      variables of interest observed on nodes already in the sample. Adjustment methods
      for nonsampling errors such as imperfect detection of drug users in the sample
      apply to adaptive as well as conventional designs.

PMID- 9243568
TI  - Self-reported drug use: results of selected empirical investigations of validity.
AB  - This chapter reviews the literature on factors related to quality of self-report
      data on drug use and discusses two series of empirical studies investigating the
      quality of those data. One set of analyses examined the quality of the
      longitudinal retrospective self-report from narcotics addicts, including validity
      of recent narcotics use, reliability of various measures, stability of
      relationships among these measures, and pattern reliability among latent
      constructs. Results contribute strongly to confidence in the validity of the
      relationships among these data derived from addicts' self-report. The second set
      of analyses focused on validity of self-reported drug use among high-risk groups,
      including samples from sexually transmitted disease (STD) clinics, hospital
      emergency rooms (ERs), and jails. Results suggest that the accuracy of self
      report of recent drug use varies by the sample sources, drug types, and subject
      characteristics. Targeting these high-risk groups may improve prevalence
      estimation. The chapter concludes that empirical validation of self-report is
      always necessary to enhance the utility of collected self-report data and provide
      means of controlling for potential biases.

PMID- 9243569
TI  - Design and results of the Women's Health Study.
AB  - The Women's Health Study was a methodological experiment carried out in Chicago.
      More than 1,000 women took part; a comparison sample of 100 men was also
      included. The sample was selected from two sources. Most of the women and all of
      the men were selected from an area probability sample that had been screened to
      identify women in the eligible age range; the rest of the women were selected
      from rosters at cooperating abortion clinics and were known to have had an
      abortion. Questionnaires based on the one used in the National Survey of Family
      Growth were administered to the sample; the questionnaire included items on
      abortion, sexual behavior, and illicit drug use. The experiment examined five
      variables: whether the questionnaire began with a series of medical questions or
      with questions on pregnancy; whether the interview was conducted by a nurse or
      field interviewer; whether the interview was done at the respondent's home or
      outside the home; whether the interviewer or respondent administered the
      questions; and whether the data were collected on paper or via computer. Of the
      five experimental factors, the one with the most consistent effect was the method
      of administering the questions. Self-administration significantly increased the
      reported number of sexual partners, sexually transmitted diseases, and the level
      of condom use compared to administration by an interviewer. Computer assistance
      occasionally interacted with the site of the interview to effect reporting. The
      other two experimental variables-the version of the questionnaire and the data
      collection staff-had few discernible effects. None of the variables affected
      reported drug use over the lifetime.

PMID- 9243570
TI  - Mode of interview and reporting of sensitive issues: design and implementation of
      audio computer-assisted self-interviewing.
AB  - Substantial underreporting is typical in interviewing respondents on their drug
      use and other sensitive behaviors. This chapter reviews established strategies,
      self-administered questionnaires and indirect questioning techniques, for
      increasing the willingness of respondents to report stigmatizing behaviors. While
      these methods improve reporting, each has shortcomings and burdens which limit
      their effectiveness. A new computer-based self-interviewing approach which
      incorporates recorded audio playback of questions offers improved self
      administered interviewing. The chapter discusses this technology, audio computer
      assisted self-interviewing (audio-CASI), describing its features and positive
      results from the early research tests of the method.

PMID- 9243571
TI  - Privacy effects on self-reported drug use: interactions with survey mode and
      respondent characteristics.
AB  - This chapter examines the impact of interview privacy on self-reported illicit
      drug use. In 1991, interviews were completed with an urban-suburban sample of
      2,417 adults aged 18 to 45. Results show that the presence of third parties
      during the interview significantly influences respondents' willingness to reveal
      illicit drug use. Among married respondents, presence of a spouse resulted in
      higher reporting of illicit drug use, while the presence of adults other than the
      spouse had a consistent negative effect on drug use reports. A parent's presence
      during the interview significantly reduced respondents' willingness to report
      illicit drug use. The pattern of findings suggests that the direction of effects
      due to third party presence is linked to two factors: the extent of the third
      party's knowledge of the information requested, and the degree of personal stake
      the third party may have in the respondent's answers. The differential impact of
      privacy by interview mode was also examined. Tests of interactions between
      privacy and interview mode failed to support the hypothesis that the use of self
      administered answer sheets reduces privacy effects compared with interviewer
      administered interviews.

PMID- 9243572
TI  - The use of the psychological laboratory to study sensitive survey topics.
AB  - Maximizing the tendency of the survey respondent to answer truthfully when
      sensitive questions are presented is critical issue in survey methodology. A
      recent development devoted generally to the reduction of response error in survey
      data is the use of cognitive laboratory techniques during the survey development
      phase. The chapter categorizes and describes the various cognitive techniques
      that have been applied, by Federal agencies and other researchers, to the study
      of sensitive questions. Based on this analysis and review, a number of
      recommendations are made concerning specific aspects of survey design, when
      sensitive questions are administered.

PMID- 9243573
TI  - Repeated measures estimation of measurement bias for self-reported drug use with
      applications to the National Household Survey on Drug Abuse.
AB  - Direct estimates of response bias for self-reports of drug use in surveys require
      that essentially error free determinations of drug use be obtained for a
      subsample of survey respondents. The difficulty of obtaining determinations which
      are accurate enough for estimating validity is well-documented in the literature.
      Methods such as specimen (e.g., hair, urine) analysis, proxy reports, and the use
      of highly private and anonymous modes of interview all have to contend with error
      rates which may only be marginally lower than those of the parent survey. Thus,
      any methodology for direct validity estimation must rely to some extent on
      approximations and questionable assumptions. In this chapter, the authors
      consider a number of methods that rely solely on repeated measures data to assess
      response bias. Since the assumptions associated with these approaches do not
      require highly accurate second determinations they may be more easily satisfied
      in practice. One such method for bias estimation for dichotomous variables that
      is considered in some detail provides estimates of misclassification
      probabilities in the initial measurement without requiring that the second
      measure be accurate or even better than the first. This methodology does require,
      however, that two subpopulations exist which have different rates of prevalence
      but whose probabilities of false positive and false negative error are the same.
      The applicability of these methods for self-reported drug use are described and
      illustrated using data from the National Household Survey on Drug Abuse. In the
      discussion of the results, the importance of these methods for assessing the
      validity of self-reported drug use are examined.

PMID- 9243574
TI  - The use of external data sources and ratio estimation to improve estimates of
      hardcore drug use from the NHSDA.
AB  - Levels of hardcore drug use have been especially difficult to estimate because of
      the relative rarity of the behavior, the difficulty of locating hardcore drug
      users, and the tendency to underreport stigmatized behavior. This chapter
      presents a new application of ratio estimation, combining sample data from the
      National Household Survey on Drug Abuse (NHSDA) together with population counts
      of the number of persons arrested in the past year from the Uniform Crime Report
      (UCR) and the number of persons in drug treatment programs in the past year from
      the National Drug and Alcoholism Treatment Unit Survey (NDATUS). The population
      counts serve as a benchmark accounting for undercoverage and underreporting of
      hard drug users.

PMID- 9243575
TI  - Improving the quality of cancer care.

PMID- 9243576
TI  - Oncology Nursing Society position paper on quality cancer care.
AB  - The cost-reduction emphasis in healthcare restructuring threatens the delivery of
      quality cancer care. A primary focus on cost by payors and delivery systems
      signals an onerous intention to limit access to essential components of cancer
      care. This is exemplified in recent trends including that Payors restrict access
      to specialty oncology care. Payors impose limitations on selection of treatment
      options and access to supportive-care services. Registered nurses are encouraged
      to generalize rather than specialize in oncology. Experienced oncology registered
      nurses, including expert advanced practice nurses and senior nurse executives,
      have lost jobs. Specialized oncology units have dissolved or combined with non
      specialty units. Chemotherapy drugs are administered either by nurses lacking
      oncology knowledge and chemotherapy competencies or lesser-skilled assistive
      personnel. The oncology registered nurse role in the multidisciplinary team is
      pivotal in creating an environment conducive to quality patient care. Therefore,
      it is the position of the Oncology Nursing Society that Quality cancer care is a
      right of all citizens. Quality cancer care entails timely access to and
      reimbursement for a coordinated, comprehensive approach to care provided by a
      multidisciplinary team throughout the cancer trajectory that includes prevention,
      early detection, treatment, supportive care, long-term follow-up, and end-of-life
      care. Quality cancer care is culturally competent, ethical, and cost-effective.
      Quality cancer care incorporates the individual with cancer (and the family) as
      fully-informed partners and decision-makers. Quality cancer care is coordinated
      and delivered by competent cancer care providers. Accountability and coordination
      of quality cancer care is best accomplished by registered nurses who have been
      educated and certified in the oncology specialty. Oncology advanced practice
      nurses should be utilized in all cancer care delivery systems. Oncology nursing
      must be included with equal parity to that of medicine and other disciplines in
      the planning and implementation of cancer care services.

PMID- 9243577
TI  - Clinical case management assessment enables nurses to personalize a patient's
      care plan.

PMID- 9243578
TI  - Using a stopcock reduces risk of infection with venous access devices.

PMID- 9243579
TI  - Patients undergoing bone marrow transplant benefit from exercise class.

PMID- 9243580
TI  - Standard operating procedure manual ensures consistency in clinical research.

PMID- 9243581
TI  - FOCUS-PDCA ensures continuous quality improvement in the outpatient setting.

PMID- 9243582
TI  - Multidisciplinary discharge rounds ensure continuity of care.

PMID- 9243583
TI  - Oncology nurses: masters in the art of caring.

PMID- 9243584
TI  - Self-care: ready or not!

PMID- 9243585
TI  - Effects of exercise on fatigue, physical functioning, and emotional distress
      during radiation therapy for breast cancer.
AB  - PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking
      exercise program during radiation therapy treatment for breast cancer would
      demonstrate more adaptive responses as evidenced by higher levels of physical
      functioning and lower levels of symptom intensity than women who did not
      participate. DESIGN: Experimental, two-group pretest, post-test. SETTING: Two
      university teaching hospital outpatient radiation therapy departments. SAMPLE: 46
      women beginning a six-week program of radiation therapy for early stage breast
      cancer. METHODS: Following random assignment, subjects in the exercise group
      maintained an individualized, self-paced, home-based walking exercise program
      throughout treatment. The control group received usual care. Dependent variables
      were measured prior to and at the end of radiation therapy. In addition, symptoms
      were assessed at the end of three weeks of treatment. MAIN RESEARCH VARIABLES:
      Participation in the walking exercise program, physical functioning fatigue,
      emotional distress, and difficulty sleeping. FINDINGS: Hypothesis testing by
      multivariate analysis of covariance, with pretest scores as covariates, indicated
      significant differences between groups on outcome measures (p < 0.001). The
      exercise group scored significantly higher than the usual care group on physical
      functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and
      difficulty sleeping. Fatigue was the most frequent and intense subjective symptom
      reported. CONCLUSIONS: A self-paced, home-based walking exercise program can help
      manage symptoms and improve physical functioning during radiation therapy.
      IMPLICATIONS FOR NURSING PRACTICE: Nurse-prescribed and -monitored exercise is an
      effective, convenient, and low-cost self-care activity that reduces symptoms and
      facilitates adaptation to breast cancer diagnosis and treatment.

PMID- 9243586
TI  - Medullary thyroid carcinoma: one component of the inherited disorder multiple
      endocrine neoplasia type 2A.
AB  - PURPOSE/OBJECTIVES: To describe and discuss the inherited syndrome multiple
      endocrine neoplasia (MEN) and one of its components medullary thyroid carcinoma.
      DATA SOURCES: Published books and articles; clinical experience. DATA SYNTHESIS:
      Three distinct types of MEN are known. Type 2a consists of medullary thyroid
      carcinoma, pheochromocytoma, and other conditions. The disorder is autosomal
      dominant. Genetic counseling and screening and biochemical screening are
      possible. Early detection and treatment are key to successful control.
      CONCLUSIONS: Identification of kindreds affected by this inherited disorder can
      result in improved detection and early treatment. The merit and value of
      presumptive treatment remain unclear. IMPLICATIONS FOR NURSING PRACTISE: Nursing
      activities encompass prediagnosis through postoperative phases. Care involves all
      members of the family as well as psychological care.

PMID- 9243587
TI  - Breast cancer risk: protective effect of an early first full-term pregnancy
      versus increased risk of induced abortion.
AB  - PURPOSE/OBJECTIVES: To examine the question of whether an early first full-term
      pregnancy (FFTP) protects against breast cancer and whether interruption of the
      pregnancy with an induced abortion increases breast cancer risk. DATA SOURCES:
      Published medical and epidemiology journal articles, books, scientific reports,
      news interviews of researchers, scientific journals. DATA SYNTHESIS: Continually
      increasing breast cancer rates cannot be explained by the American Cancer Society
      risk factors, which account for only 25% of cases. Induced abortion is a newly
      recognized risk factor and has been prevalent in our society since it was
      legalized in 1973. CONCLUSIONS: Early FFTP confers protection, while induced
      abortion confers risk. Most specific and controlled variables studies indicate
      150% risk for abortions performed on women younger than 18 years of age. Studies
      have yet to discover the full impact of induced abortion because women who
      underwent legalized abortion in 1973 are just reaching ages of highest breast
      cancer incidence. IMPLICATIONS FOR NURSES: Awareness of a controversial risk
      factor and its relevance to women allows nurses to include this information when
      educating and supporting patients. Specifically, nurses need to include questions
      on this reproductive risk when eliciting a patient's reproductive history. Nurses
      should further be aware of the emotional impact disclosure may have.

PMID- 9243589
TI  - Strategies for assessing and fostering hope: the hope assessment guide.
AB  - PURPOSE/OBJECTIVES: To detail behavioral manifestations of hope and to present
      the Hope Assessment Guide with stage-specific nursing strategies to foster the
      development of hope. DATA SOURCES: Previous research and a concept analysis of
      hope, including interviews with survivors of breast cancer, people awaiting heart
      transplants, breast-feeding mothers returning to work, and patients with spinal
      cord injuries. Criteria for inclusion included empirical validity of the
      conceptual framework, power of the autobiographic data to illustrate theoretical
      fit, and usefulness of the theory in assessing hope and devising clinical
      strategies. DATA SYNTHESIS: Behavioral manifestations within reported breast
      cancer experiences demonstrated theoretical fit. From this, the researchers
      extracted assessment factors and identified clinical strategies based on reported
      experiences and strategies found helpful at various stages of the hope
      development process. CONCLUSIONS: The conceptual model provides structure for
      assessing and responding to developing hopefulness in a stage-specific manner.
      IMPLICATIONS FOR NURSING PRACTICE: By becoming aware of the processes of
      developing hope, nurses are better prepared to clinically assess this dynamic
      process and to devise highly individualized clinical interventions in cases in
      which hope needs to be supported or modified.

PMID- 9243588
TI  - The effects of nursing care guided by self-regulation theory on coping with
      radiation therapy.
AB  - PURPOSE/OBJECTIVES: To test the hypotheses that preparatory informational
      interventions based on self-regulation theory delivered to radiation therapy (RT)
      recipients by staff nurses would reduce disruption in patients' usual life
      activities and have a positive effect on the moods of patients who tended to have
      pessimistic expectations about outcomes. DESIGN: A quasi-experimental design with
      repeated measures. SETTING: University-affiliated RT department. SAMPLE: 226
      patients receiving RT for breast or prostate cancer. METHODS: The control-group
      patients received the nursing care that was the standard of practice before the
      experimental interventions were introduced. The experimental-group patients
      received theory-based interventions four different times from staff nurses.
      Patient data were collected by interview four different times. MAIN RESEARCH
      VARIABLES: Type of nursing interventions generated, optimistic or pessimistic
      expectations about outcomes (Life Orientation Test), amount of disruption in
      usual life activities (Sickness Impact Profile), and moods (Bi-Polar Profile of
      Mood States). FINDINGS: The patients who received the self-regulation theory
      based nursing interventions experienced less disruption in their usual life
      activities during and following RT. Among the patients who tended to be
      pessimistic, those who received the theory-based interventions had a more
      positive mood than those who did not receive the interventions. IMPLICATIONS FOR
      NURSING PRACTICE: Staff nurses should use self-regulation theory-based
      interventions to help patients cope with RT.

PMID- 9243591
TI  - Involvement of nitric oxide in 2-deoxy-D-glucose-induced hyperphagia in rats.
AB  - The effects of a nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME) on 2-deoxy-D-glucose (2-DG)-induced hyperphagia were investigated
      in rats. L-NAME dose-dependently inhibited 2-DG-induced eating in non-food
      deprived rats, although the inactive isomer D-NAME on 2-DG-induced hyperphagia
      were inhibited by co-administration of L-arginine. The neuronal NO synthase
      inhibitor 7-nitroindazole also inhibited 2-DG-induced hyperphagia. These results
      suggest that 2-DG-induced hyperphagia is linked with NO and that brain NO may
      participate in this hyperphagic model.

PMID- 9243590
TI  - The DNA methyltransferase inhibitor 5-azacytidine specifically alters the
      expression of helix-loop-helix proteins Id1, Id2 and Id3 during neuronal
      differentiation.
AB  - In mammals, cytosine methylation is important for the regulation of gene
      expression and chromatin structure. Recently, we have found evidence indicating
      that the maintained DNA methyltransferase activity is critical for neuronal cell
      differentiation. In the present study, we have investigated the effect of the DNA
      methyltransferase inhibitor 5-azacytidine on gene regulation during nerve growth
      factor (NGF)-induced neuronal differentiation of PC12 cells. Expression of the
      helix-loop-helix proteins Id1, Id2 and Id3 was specifically reduced by NGF and
      this effect was blocked in 5-azacytidine-treated cells, concomitant with the
      inhibition of NGF-induced neuronal differentiation. Nuclear run-on and Id2
      promoter analyses further demonstrated that the decreased transcription of Id
      proteins is at least in part dependent on the DNA methyltransferase activity.
      These findings indicate that Id proteins are downstream targets of the NGF
      transduction pathway. Moreover, these results suggest that therapeutic strategies
      using 5-azacytidine against certain types of tumors should be reconsidered
      because of the possible deleterious effects on neuronal cell function.

PMID- 9243592
TI  - Reduced NMDA receptor sensitivity may underlie the resistance of subpopulations
      of PVN neurons to excitotoxicity.
AB  - Magnocellular neurons in the paraventricular nucleus are resistant to excitotoxic
      cell damage. We tested the hypothesis that a modified post-synaptic response
      following NMDA receptor activation may underlie this resistance. Whole-cell
      recordings from hypothalamic slices showed that NMDA receptor activation caused
      dose-dependent depolarizations in both Type I (putative magnocellular) and Type
      II (putative parvocellular) neurons. Type II cells, however, were an order of
      magnitude more sensitive (10 nM) than Type I neurons (100 nM). The
      depolarizations recorded in Type II cells were also significantly greater (> 35%
      resulting in sodium channel inactivation) than those recorded in Type I neurons.
      This differential sensitivity of neurons to NMDA receptor activation may explain
      the selective resistance of magnocellular PVN neurons to excitatory neurotoxins.

PMID- 9243593
TI  - Inhibition of NMDA receptor-mediated synaptic transmission in the rat dentate
      gyrus in vitro by IL-1 beta.
AB  - The action of interleukin-1 beta (IL-1 beta) and its receptor antagonist IL-1ra
      were investigated on dual component, isolated AMPA and NMDA field excitatory post
      synaptic potentials (EPSP) and on the induction and maintenance of long-term
      potentiation in the rat dentate gyrus in vitro. Perfusion with IL-1 beta (1
      ng/ml) for 1 h had no significant effect on the dual component EPSP or the
      isolated AMPA-EPSP. In contrast IL-1 beta had a significant inhibitory effect on
      the isolated NMDA-EPSP amplitude (54 +/- 7% at 1 h compared with controls; n = 9;
      p < 0.001). This effect was fully antagonized in the presence of 100 ng/ml IL-1
      receptor antagonist. IL-1 beta also inhibited LTP of the dual component EPSP but
      had no effect on the maintenance phase when applied post-induction of LTP. This
      study demonstrates for the first time that the inhibitory effect of IL-1 beta on
      LTP in the dentate gyrus may be at least partially due to a block of post
      synaptic NMDA receptors.

PMID- 9243595
TI  - Neurokinin-1 receptor antagonist SR140333: a novel type of drug to treat cerebral
      ischemia.
AB  - Substance P (SP) has been implicated in immune responses and could increase
      glutamate release, and inflammatory reactions are known to be able to potentiate
      ischemic damage. We have previously found that SP was over-expressed in cerebral
      ischemia and speculated that SP may play a role in exacerbating ischemic damage.
      In this study, we examined whether a neurokinin-1 (NK-1) receptor antagonist,
      SR140333, would have an effect on brain ischemia. Intra-cerebroventricular
      (i.c.v.) administration of SR140333 (30 micrograms) markedly reduced (37.1 +/-
      7.8%, p < 0.001) infarct volume measured 24 h after focal cerebral ischemia in
      the rat. The SR140333-treated group also exhibited a significantly improved
      neurological function reflected by the neurological deficit score. The results
      represented the first demonstration that a NK-1 receptor antagonist may be a
      novel type of drug for treatment of cerebral ischemia.

PMID- 9243594
TI  - The immunosuppressant FK506 prolongs transgene expression in brain following
      adenovirus-mediated gene transfer.
AB  - First generation, replication-defective adenoviral vectors are highly effective
      for gene transfer into the central nervous system, but the host's immune response
      limits the utility of this vector for possible therapy of neurological disease or
      long-term gene transfer studies in experimental animals. We have demonstrated the
      effectiveness of FK506 (tacrolimus), a powerful immunosuppressant that readily
      crosses the blood-brain barrier, in maintaining adenovirus-mediated reporter gene
      transfer following stereotaxic injection of the recombinant (AdCMVlacZ) into
      mouse striatum. After 28 days, beta-galactosidase expression was reduced by 75%
      relative to day 10 in immunocompetent animals, accompanied by an inflammatory
      reaction in the region of transduced cells; however, in mice receiving daily s.c.
      injections of FK506, beta-galactosidase activity was maintained at the 10 days
      post-injection level.

PMID- 9243596
TI  - Changes in nitric oxide metabolite levels in stimulated substantia nigra neurons.
AB  - Simultaneous quantification of the two major nitric oxide (NO) metabolites,
      nitrite and nitrate, was performed on mouse mesencephalic neurons in vitro, in
      basal conditions or after excitatory stimuli. Measurements were made using both
      extracellular medium and cytosolic extracts. Basal metabolite levels were stable
      up to 5 min. Depolarization by high levels of potassium promptly increased
      extracellular nitrite (270% of basal, peak at 10s) leaving intracellular levels
      unchanged. Glutamate receptor agonists caused a rapid increase in intracellular,
      but not extracellular, nitrite levels (240% of basal, peak at 30s). Intracellular
      nitrate levels raised slowly after addition of potassium (215% of basal at 1 min)
      or N-methyl-D-aspartate (230% of basal at 5 min), but not after quisqualate. The
      different dynamic variations of the two NO metabolites point to the specificity
      of the activated metabolism according to the type of excitatory stimulus.

PMID- 9243597
TI  - Endothelin-induced calcium signaling in cultured mouse microglial cells is
      mediated through ETB receptors.
AB  - Microglial cells are the intrinsic immunocompetent cells of the central nervous
      system, which are activated by brain tissue damage. In this paper we investigated
      the ability of endothelins (ETs), which are potent vasoconstrictors, to induce
      intracellular calcium signals in cultured microglia cells. Both endothelin-1 and
      endothelin-3 increased intracellular Ca2+ concentration ([Ca2+]i). These [Ca2+]i
      transients were mimicked by BQ3020, an ETB receptor agonist and blocked by BQ788,
      a selective ETB antagonist, respectively. The calcium signals induced by the
      endothelins persisted in Ca(2+)-free media. Transcripts encoding the ETB receptor
      were detected in purified microglial cultures and cDNA fragments derived from ETB
      receptor mRNA were amplified from 9% of electrophysiologically characterized
      microglial cells by the use of single-cell RT-PCR.

PMID- 9243598
TI  - Secreted form of beta-amyloid precursor protein shifts the frequency dependency
      for induction of LTD, and enhances LTP in hippocampal slices.
AB  - The secreted form of beta-amyloid precursor protein (sAPP alpha) is released from
      neurons in an activity-dependent manner, and has been reported to modulate
      neuronal excitability in dissociated hippocampal neurons. We now report that sAPP
      alpha shifts the frequency dependence for induction of long-term depression of
      synaptic transmission (LTD) in hippocampal slices from adult rats. Whereas low
      frequency stimulation (1 Hz) of Schaffer collateral axons induced LTD of the post
      synaptic response of CA1 neurons in control slices, it did not induce LTD in
      slices pretreated with sAPP alpha. On the other hand, whereas a 10 Hz stimulation
      normally induced neither LTD or LTP, it did induce LTD in slices pretreated with
      sAPP alpha. sAPP alpha potentiated LTP induced by high frequency stimulation.
      sAPP alpha induced cGMP production in hippocampal slices, and pretreatment of
      slices with 8-bromo-cyclic GMP mimicked the effect of sAPP alpha on LTD
      suggesting a role for cyclic GMP in modulation of LTD. The data suggest an
      important role for sAPP alpha in modulation of synaptic plasticity in the
      hippocampus.

PMID- 9243599
TI  - Eye-hand interactions during goal-directed pointing movements.
AB  - Saccadic eye and hand movements made to step displacements in target position
      were measured under conditions designed to dissociate the output of the ocular
      and manual motor systems. This was accomplished by having subjects look and
      point, either with or without vision of the hand (closed or open loop,
      respectively) at peripheral targets starting from independent initial positions.
      The results showed that the amplitude of open loop pointing responses increased
      in size when accompanied by saccades that were larger than the required hand
      movement. Providing the subject with visual feedback of the hand during the
      response or asking them to visually fixate caused this effect to disappear. Taken
      together, this pattern of results suggests that when vision of the hand is
      unavailable the programming of saccade metrics influences the control of
      simultaneously produced pointing movements in an on-line manner.

PMID- 9243601
TI  - NMDA receptors are important for both mechanical and thermal allodynia from
      peripheral nerve injury in rats.
AB  - Previous studies showed that heat-hyperalgesia and mechanical allodynia produced
      by chronic constrictive injury of the sciatic nerve were differentially sensitive
      to the NMDA receptor antagonist dextrorphan and to morphine and other opioid
      receptor agonists. These results support the hypothesis that different kinds of
      neuropathic pain symptoms are caused by different pathological mechanisms. In the
      present study we determined whether mechanical and thermal allodynia produced by
      unilateral transection of the 'superior' caudal trunk which innervates the tail
      in rats were differentially sensitive to the non-competitive NMDA receptor
      antagonist MK-801. Injection of MK-801 (0.3 mg/kg, i.p.) prior to nerve injury
      delayed the emergence of both types of allodynia; the antagonist-treated rats
      exhibited neither mechanical nor thermal allodynia at least for 4 days after the
      injury, whereas untreated control rats exhibited clear signs of allodynia from
      the first day after the injury. MK-801 injection on post-injury day 14, when the
      allodynia was near peak severity, suppressed temporarily both the mechanical and
      thermal allodynia. These results suggest that the mechanical and thermal
      allodynia from partial denervation of the tail are both dependent on NMDA
      receptors in their induction and maintenance. Thus, our results do not support
      the notion that different pathological mechanisms underlie different modalities
      of neuropathic pain from partial peripheral nerve injury.

PMID- 9243600
TI  - Long-term morphine treatment increases Ku protein DNA end-binding activity.
AB  - Human neuroblastoma SH-SY5Y and small-cell lung carcinoma U1690 cells of
      neuroendocrine origin were exposed to morphine for 1 h, 3 h or 5 days. These
      treatments did not alter activities of AP-1, NF-kappa B and YY1 transcription
      factors in SH-SY5Y cells or NF-kappa B and YY1 in U1690 cells. Five-day morphine
      treatment, however, caused a twofold increase in the activity of a sequence-non
      specific, spermidine-activated DNA-binding factor in U1690 cells. The morphine
      effect was prevented by the antagonist naloxone. The DNA-binding factor bound
      preferentially to double-stranded DNA ends. This fact and data on subunit
      composition, molecular masses of subunits, and supershift/inhibition by specific
      antibodies in a band shift assay, show the spermidine-activated factor to be
      identical with the Ku protein, the DNA-binding subunit of DNA-dependent protein
      kinase. The effect observed may be one of the mechanisms through which opioids
      influence gene regulation.

PMID- 9243602
TI  - Beta APP gene transfer into cultured human muscle induces inclusion-body myositis
      aspects.
AB  - Direct transfer of the beta-amyloid precursor protein (beta APP) gene into
      cultured normal human muscle, using recombinant adenovirus vector, was sufficient
      to induce several of the typical light microscopic, electron microscopic (EM),
      and EM-immunochemical aspects of the inclusion-body myositis (IBM) phenotype,
      including congophilia, clusters of amyloid-beta-positive 6-10 nm filaments, and
      15-21 nm tubulofilamentous inclusions in the nuclei. Our results suggest that
      excessive production of intracellular beta APP may play an important role in the
      pathogenic cascade leading to the IBM phenotype.

PMID- 9243603
TI  - A study of motor performance and motor learning in episodic ataxia.
AB  - Episodic ataxias are rare disorders in which periodic episodes of ataxia are
      separated by normal or near normal motor behaviour. They probably arise from
      dysfunctional membrane ion channels in the cerebellum. A patient with episodic
      ataxia EA-2 performed three motor tasks, before, during and after an ataxic
      episode. In all three tasks there were significant performance deficits during
      the ataxic episode. Two of the tasks also assessed motor adaptation (prism
      adaptation) or motor learning (ideogram drawing). In neither task was there
      significant disruption of motor adaptation or learning. These results suggest
      that the cerebellum may have separate roles in learning and in performance of
      visually guided movements, and that the dysfunction in this patient affected only
      his motor performance.

PMID- 9243604
TI  - L-deprenyl potentiates cAMP-induced elevation of FGF-2 mRNA levels in rat
      cortical astrocytes.
AB  - The expression of fibroblast growth factor-2 (FGF-2, basic FGF) is up-regulated
      in astroglial cells by different stimuli, including glucocorticoid hormones and
      agents that cause an increase in cyclic AMP (cAMP) levels. In the present study
      we showed that L-deprenyl, a drug able to rescue neurons from potentially lethal
      damage, can potentiate FGF-2 induction by 8Br-cAMP in cultured astrocytes. This
      effect appears to be independent from its well known inhibitory activity on
      monoamine oxidase (MAO) type B. As astrocyte activation is an important step in
      response to neuronal injury, our data suggest that potentiation of neurotrophic
      factor expression may exert neuroprotection and therefore limit the progression
      of neuronal damage in several pathological situations.

PMID- 9243605
TI  - Localization of tissue inhibitor of metalloproteinases-3 in neurodegenerative
      retinal disease.
AB  - Tissue inhibitor of metalloproteinases-3 (TIMP-3) is one of a family of genes
      whose products are implicated in the regulation of remodelling of the
      extracellular matrix. The level of mRNA coding for TIMP-3 is increased in retinas
      affected by the photoreceptor degenerative disease, simplex retinitis pigmentosa
      (RP), and mutations in TIMP-3 are associated with an inherited form of macular
      dystrophy. Here we compare TIMP-3 protein expression in normal retina and in
      those affected by RP and by age-related macular degeneration. Immunoreactive TIMP
      3 is present in normal retinal pigment epithelium, and in degenerative retinas
      particularly at Bruch's membrane and additionally in photoreceptor-retaining
      regions in simplex RP. The pattern suggests a role for TIMP-3 in normal retinal
      homeostasis, and, in the disease state, in the modulation of extracellular matrix
      metabolism and neovascularization.

PMID- 9243606
TI  - Effect of urine-derived compounds on cAMP accumulation in mouse vomeronasal
      cells.
AB  - Urine-derived compounds from the male mouse altered the levels of the second
      messenger molecule cAMP differentially in female mouse vomeronasal (VN) cells
      when compared with olfactory cilia. cAMP levels in VN cells increased after
      exposure to forskolin and GTP-gamma-S, while the levels decreased after exposure
      to the urine-derived compounds, dehydro-exo-brevicomin (DHB) and 2-(sec-butyl)-4,
      5-dihydrothiazole (SBT), in a dose-dependent manner. The general odorant
      citronellal did not alter cAMP levels. In contrast DHB, SBT and citronellal
      increased cAMP levels in olfactory cilia. We concluded that urine-derived
      compounds exert a differential effect on cAMP accumulation in mammalian VN and
      olfactory receptor neurons.

PMID- 9243607
TI  - Role of spinal cyclooxygenase (COX)-2 on thermal hyperalgesia evoked by
      carageenan injection in the rat.
AB  - Prostaglandins, which are known to play an important role in the nociceptive
      transmission in the spinal cord, are produced by cyclooxygenase (COX). Two forms
      of COX have been identified, COX-1 (constitutive form) and COX-2 (a form highly
      inducible in response to inflammatory stimuli). COX-2 mRNA was reported to be
      expressed in the brain in normal rats in the absence of inflammation. We
      investigated the role of spinal COX-2 in the maintenance of thermal hyperalgesia
      induced by paw carageenan injection in the rat using NS-398, a selective COX-2
      inhibitor. Intrathecally administered NS-398 attenuated the level of thermal
      hyperalgesia in a dose-dependent manner. This suggested that spinal COX-2 plays
      an important role in the maintenance of thermal hyperalgesia induced by paw
      carageenan injection.

PMID- 9243608
TI  - Dopamine facilitates striatal EPSPs through an L-type Ca2+ conductance.
AB  - When synaptic activity is evoked from relatively depolarized membrane potentials,
      D1 receptor agonists enhance the depolarization level and slow the decay of
      synaptic responses recorded from neostriatal spiny neurons. The population
      spikes' amplitude is also increased. These D1 actions facilitate firing and are
      evident in the presence of both NMDA and GABA selective blockers. Thus,
      dopaminergic D1 receptor activation facilitates the AMPA-mediated EPSP in these
      conditions. This facilitatory effect could be suppressed by L-type Ca2+ channel
      antagonists (200 nM calciseptine and 5 microM nicardipine), suggesting that it is
      mediated by an increase in L-current. D1-receptor activation thus mediates
      orthodromic facilitation of neostriatal neurons when evoked from depolarized
      membrane potentials. This reinforces the dopamine facilitation mediated through
      NMDA responses.

PMID- 9243609
TI  - Direct retinal projections to GRP neurons in the suprachiasmatic nucleus of the
      rat.
AB  - The retinal projections to gastrin-releasing peptide (GRP)-expressing neurons in
      the rat suprachiasmatic nucleus (SCN) were investigated by double
      immunofluorescence and immunoelectron microscopy. Optic nerve terminals labeled
      by cholera toxin B subunit (CTb) which was transported from the retinal ganglion
      cells were intermingled with GRP-immunoreactive cell bodies and processes in the
      ventrolateral portion of the SCN. Ultrastructural analysis revealed that CTb
      immunoreactive retinal terminals made synaptic contacts with GRP-immunoreactive
      dendritic processes. These results demonstrated that photic information is
      directly input from the optic nerve to GRP neurons in the SCN and these GRP
      neurons may be involved in circadian entrainment by light.

PMID- 9243610
TI  - Simultaneous spike detection and topographic classification in pediatric surface
      EEGs.
AB  - In this study, an algorithm is introduced for the automatic detection and
      simultaneous topographic classification of interictal regional spike activity in
      pediatric surface EEG records. The algorithm is based on the classification of
      the topographic distribution of instantaneous power by means of a 'group' trained
      classifier. The results of automatic spike analysis were compared with the
      decisions of two experienced electroencephalographers. Four routine EEG records
      exhibiting (multi)regional spikes were examined. The mean selectivity for the
      automatic spike detector was 84.6% (mean sensitivity 88.1%, mean specificity
      89.3%) and for the electroencephalographers 85.3%. All spikes detected by the
      algorithm were simultaneously classified according to their topographic
      characteristics. The results of automatic spike classification
      (lateralization/localization) corresponded to the results of visual analysis.

PMID- 9243611
TI  - Selective induction of c-Jun and NGF in reactive astrocytes after cholinergic
      degenerations in rat basal forebrain.
AB  - Cholinergic basal forebrain neurons are the major source of cortical cholinergic
      innervation. The number of these neurons is regulated by the availability of
      nerve growth factor (NGF) during development while in adulthood their cholinergic
      activity is modulated by NGF. In previous studies we have shown that cholinergic
      immunolesions of basal forebrain neurons increase local immediate early gene
      expression and NGF synthesis in the regions of degeneration. In this study we
      identify the cellular source of c-Jun and NGF expression using dual
      immunolabeling of c-Jun and NGF in combination with neuronal and glial markers.
      We demonstrate that both c-Jun and NGF are exclusively expressed in reactive
      astrocytes but not in microglia or in GABAergic basal forebrain neurons. These
      observations support the hypothesis that reactive astrocytes synthesize
      neurotrophic substances in vivo in response to neuronal degeneration in the basal
      forebrain.

PMID- 9243612
TI  - Gangliosides enhance KCl-induced Ca2+ influx and acetylcholine release in brain
      synaptosomes.
AB  - Effects of gangliosides GM1 and GQ1b on cholinergic synaptic functions were
      investigated using synaptosomes prepared from mouse brain cortices. Treatment of
      synaptosomes with GM1 and GQ1b increased high K(+)-evoked acetylcholine (ACh)
      release in a bell-shaped dose-dependent manner. The peaks of the effects were
      found to be at 1-5 microM for GM1 and 5-10 microM for GQ1b. ACh synthesis and the
      levels of ACh in synaptosomes were not affected by the ganglioside treatment.
      Both gangliosides enhanced depolarization-induced influx of calcium ions into
      synaptosomes. These results indicate that GM1 and GQ1b gangliosides increase
      evoked ACh release by modulating voltage-dependent calcium channels in the
      synaptic plasma membranes. The effect of GM1 on calcium ion influx remained after
      repetitive washings, but was almost completely abolished when the bound GM1 was
      removed by trypsin. This indicates that the fraction of GM1 which was tightly
      bound to, but not incorporated in synaptic plasma membranes, is responsible for
      activating the calcium channels.

PMID- 9243613
TI  - Age-related loss of calbindin from human basal forebrain cholinergic neurons.
AB  - Loss of basal forebrain cholinergic neurons (BFCN) occurs in many age-related
      neurological diseases. Although age is the common risk factor in these disorders,
      no consistent age-related changes have been reported in the human BFCN. We
      investigated age-related alterations in choline acetyltransferase (ChAT), low
      affinity nerve growth factor receptor (p75LNGFR) and calbindin-D28k (CalBP)
      immunoreactivity in the human BFCN. No significant age-related changes were
      observed in ChAT or p75LNGFR immunoreactivity. By contrast, normal aging was
      accompanied by a selective, substantial and significant loss of CalBP
      immunoreactivity from the BFCN. Other CalBP-positive neurons were unchanged. Loss
      of the calcium buffering capacity conferred by CalBP may leave the BFCN
      vulnerable to damage in neurodegenerative disorders.

PMID- 9243614
TI  - Conditioned taste aversion and c-fos expression in the rat brainstem after
      administration of various USs.
AB  - Conditioned taste aversion (CTA) is a form of association learning established
      when an animal associates a conditioned stimulus (taste) with a subsequent
      unconditioned stimulus (US, illness). We have studied the relationship between
      the efficacy of inducing CTA to 0.1% saccharin and c-fos expression in the lower
      brain stem following administration of 13 different USs in rats. The effective
      USs were grouped into abdominal irritants, rewarding drugs and emetic agents.
      Regardless of the properties of USs, good correlation was detected between the
      strength of CTA and c-fos expression within the area postrema, caudal and
      intermediate subdivisions of nucleus tractus solitarius and the external lateral
      subnucleus of the parabrachial nucleus. Only hypertonic saline was exceptional
      because of the experimental procedure: it induced strong c-fos expression, but
      was not an effective US for CTA formation. Different dosages of the emetic LiCl
      induced CTA and c-fos expression in a dose-dependent manner.

PMID- 9243615
TI  - Further evidence for the involvement of a hippocampal cGMP/cGMP-dependent protein
      kinase cascade in memory consolidation.
AB  - Hippocampal cyclic GMP (cGMP) has been recently postulated to participate in an
      early phase of memory consolidation of an inhibitory avoidance learning in rats.
      Here we report on the effects of the intrahippocampal infusion of a soluble
      guanylyl cyclase inhibitor (LY 83583) in the consolidation of one-trial step-down
      inhibitory avoidance and on the effect of this task on hippocampal cGMP levels
      and cGMP-dependent protein kinase (PKG) activity. Bilateral intrahippocampal
      administration of LY 83583 (2.5 micrograms per side) caused full amnesia for
      inhibitory avoidance when given immediately (0 min) after training, but not 30
      min post-training. Rats submitted to the inhibitory avoidance task showed a
      significant increase in both cGMP levels and in PKG activity in the hippocampus
      at 0 min after training. No changes were observed 30 min after training. These
      findings provide further evidence that the hippocampal cGMP/PKG cascade is
      involved in the early stages of memory formation of an inhibitory avoidance task
      in rats.

PMID- 9243616
TI  - Incorporation of NF-L into keratin filaments in transfected epithelial cells.
AB  - Neurofilaments are the characteristic intermediate filaments of mature neurons;
      during development and in some neuronal cell lines and neuroendocrine tumors,
      neurofilament proteins are expressed together with vimentin or cytokeratins. In
      some cell types, the filamentous arrays formed by neurofilaments and vimentin or
      cytokeratins do not coincide. However, individual neurofilament proteins co
      assemble with vimentin in transfected non-neuronal cells. In order to determine
      whether individual neurofilament proteins could also co-assemble with
      cytokeratins in a cellular environment, the light chain of neurofilaments, NF-L,
      was transfected into MCF-7 cells, in which the only cytoplasmic intermediate
      filament proteins expressed are cytokeratins. In transfected MCF-7 cells, human
      NF-L was localized to a prominent filamentous network. This pattern most probably
      reflected the incorporation of NF-L into the endogenous keratin cytoskeleton as
      it is unlikely to be due to human NF-L self-assembly since, like its rodent
      counterpart, human NF-L accumulated into punctate aggregates when transiently
      transfected in intermediate filament-deficient SW13 vim- cells. These results
      suggest the existence of a specific mechanism of segregation of neurofilaments
      and keratin filaments in some cell types.

PMID- 9243617
TI  - Nitric oxide generation from sodium nitroprusside and hydroxylamine in brain.
AB  - We aimed to demonstrate different modes of in situ nitric oxide (NO) generation
      from two NO donors in cerebral cortex of halothane anesthetized cats. NO donors
      were delivered by in vivo microdialysis into the cortical tissue where an NO
      electrode measured real-time changes in extracellular NO concentration. In vitro
      testing in Finger's solution revealed that sodium nitroprusside (SNP) liberates
      NO spontaneously in the presence of light, whereas hydroxylamine does not
      generate any NO under these conditions. Supplementation with 200 mM of the NO
      donors SNP and hydroxylamine evoked dose-related increases in NO concentration
      (52.0 +/- 6.7 nM, n = 5, and 14.0 +/- 3.8 nM, n = 5, respectively). The increase
      in NO concentration was significantly greater during SNP than during
      hydroxylamine delivery (p < 0.001). In contrast, CBF increased similarly under
      the influence of both NO donors. Electrocorticogram and cortical direct current
      potential remained unaffected. In conclusion, hydroxylamine is degraded into NO
      intracellularly and efficiently dilates cerebral blood vessels. SNP, in contrast,
      generates NO mainly in the extracellular space.

PMID- 9243618
TI  - 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs.
AB  - The serotonin (5-HT) receptor subtype mediating inhibition of neurogenic dural
      inflammation in guinea pigs was investigated using a series of serotonin agonists
      with differing affinities for the 5-HT1B, 5-HT1D and 5-HT1F receptors. When
      agonist potencies for inhibiting neurogenic inflammation were compared with
      affinities for these receptor subtypes, a significant positive correlation was
      seen only with the 5-HT1F receptor. The potency of agonists in inhibiting
      adenylate cyclase in cells transfected with human 5-HT1F receptor was also highly
      correlated with their potency in the animal model of migraine. In situ
      hybridization demonstrated 5-HT1F receptor mRNA in guinea pig trigeminal ganglion
      neurons. These data suggest that the 5-HT1F receptor is a rational target for
      migraine therapeutics.

PMID- 9243619
TI  - Immunostimulation protects microglial cells from nitric oxide-mediated apoptosis.
AB  - Cellular oxidative stress from excess free radicals can initiate apoptosis in
      some cell types. Thus, we hypothesize that cells expressing nitric oxide synthase
      (NOS) will also express anti-oxidative stress mechanisms, in order to prevent
      self-intoxication by the free radical, nitric oxide (NO). To test this
      hypothesis, we investigated the vulnerability of microglial cells (BV-2 line) to
      NO produced by the NO donor sodium nitroprusside. Damage to the cells was
      measured by an in situ detection method of DNA fragmentation, an indicator of
      apoptosis. Activation by lipopolysaccharide (LPS) dose-dependently protected BV-2
      cells against NO toxicity (up to 67%) while unactivated BV-2 cells were
      vulnerable to NO. Our results indicate that activation of BV-2 cells induces
      protection mechanisms against NO toxicity.

PMID- 9243620
TI  - Fast transport and retrograde movement of huntingtin and HAP 1 in axons.
AB  - Huntingtin, the protein product of the Huntington's disease gene, associates with
      vesicle membranes and microtubules in neurons. Analysis of axonal transport with
      a stop-flow, double crush ligation approach in rat sciatic nerve showed that full
      length huntingtin (350 kDa) and an N-terminal cleavage product (50 kD) were
      increased within 6-12 h on both the proximal and distal sides of the crush site
      when compared with normal unligated nerve. The huntingtin associated protein HAP
      1 and the retrograde motor protein dynein also accumulated on both sides of the
      crush, whereas the vesicle docking protein SNAP-25 was elevated only proximally.
      The cytoskeletal protein alpha-tubulin was unaffected. The rapid anterograde
      accumulation of huntingtin and HAP 1 is compatible with their axonal transport on
      vesicular membranes. Retrograde movement of both proteins, as seen by
      accumulation distal to the nerve crush, may be necessary for their degradation at
      the soma or for a function in retrograde membrane trafficking.

PMID- 9243621
TI  - Medial fetal ventral mesencephalon: a preferred source for dopamine neuron
      grafts.
AB  - Currently, fetal tissue transplantation into patients with Parkinson's disease
      utilizes the entire ventral mesencephalon (VM) as donor tissue. However, the
      resulting mixture of cell types contains a relatively low proportion of
      therapeutically relevant dopamine (DA) neurons. We show that differential
      dissection of a medial region of embryonic day 14 rat VM yields a significantly
      higher proportion of DA neurons (8-10%) than is found in lateral VM (2%) or whole
      VM (4-5%). Medial VM also contained a larger number of the specific subpopulation
      of DA neurons (aldehyde dehydrogenase-positive; AHD) that project to dorsolateral
      motor region of the striatum. Selective dissection of fetal medial VM selectively
      enriches DA neurons in cell preparations useful for transplantation in
      Parkinson's disease.

PMID- 9243622
TI  - Factors secreted by activated microglia and monocytes reduce amyloidogenesis in
      vascular smooth muscle cells.
AB  - Smooth muscle cells cultured from amyloid-beta-affected arteries accumulate
      amyloid-beta peptide A beta. We now show that accumulation of "A beta" deposits
      in this model can be significantly reduced by culture in conditioned media from
      microglia and monocytes. Reduced A beta accumulation was associated with (i)
      lower secretion of A beta, (ii) increased secretion, but not cellular levels of
      amyloid-beta-precursor protein (A beta PP), and (iii) increased cell
      proliferation and metabolic activity. We suggest that improper regulation of A
      beta PP metabolism by monokines may facilitate vascular amyloidogenesis.

PMID- 9243623
TI  - IGF-I enhances neurite regeneration but is not required for its survival in adult
      DRG explant.
AB  - We clarified the roles of insulin-like growth factor (IGF) I and II in peripheral
      neural regeneration after axotomy using cultured adult DRG explants either with
      or without associated nerve bundles. When IGF-I was applied at concentrations of
      1-10 nM to DRG explants without associated nerve bundles in a serum-free medium,
      clear enhancement of neural regeneration from both central and peripheral
      transected nerve terminals was seen. When the same concentrations of IGF-I were
      applied to DRG explants with associated nerve bundles this enhancement was
      reduced at central sites and increased at peripheral sites. Neural survival was
      not affected by IGF-I in any of these culture systems. In comparison with IGF-I,
      there was no specific effect of IGF-II on neurite regeneration.

PMID- 9243624
TI  - Acetylcholine exocytosis in PC12 cells deficient in SNAP-25.
AB  - Stimulus-induced acetylcholine (ACh) exocytosis from presynaptic nerve terminals
      involves two important steps: fusion of ACh loaded vesicles at presynaptic
      release sites, followed by release into the synaptic cleft. We studied the role
      of the putative vesicle fusion protein SNAP-25 in this process. The nerve growth
      factor-differentiated PC12 cell line was used as an experimental model. A bee
      venom tetradecapeptide (INLKALAALAKKIL-NH2) phospholipase A2 (PLA2) activator,
      mastoparan, was used to induce ACh release. Treatment of PC12 cells with
      appropriate antisense oligonucleotides blocked SNAP-25 expression, as judged by
      Western blot protein analysis with a specific monoclonal antibody. Despite
      apparent elimination of SNAP-25, treatment of differentiated PC12 cells with
      mastoparan and high (80 mM) K+ induced ACh exocytosis. The results indicate that
      in PC12 cells, ACh exocytosis due to mastoparan plus K+ can occur in the absence
      of SNAP-25.

PMID- 9243625
TI  - 4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of
      the microtubule-associated protein tau.
AB  - In Alzheimer's disease (AD) the microtubule-associated protein tau is excessively
      phosphorylated in degenerating neurons, but the mechanisms underlying the
      increased phosphorylation are unknown. Recent findings suggest that oxidative
      stress, and membrane lipid peroxidation in particular, contributes to the
      neurodegenerative process in AD. We now report that following exposure of
      cultured rat hippocampal neurons to 4-hydroxynonenal (HNE), an aldehydic product
      of membrane lipid peroxidation, tau is resistant to dephosphorylation.
      Immunocytochemical and Western blot analyses using phosphorylation-sensitive tau
      antibodies showed that HNE treatment causes a moderate increase in basal levels
      of tau phosphorylation, and prevents tau dephosphorylation by alkaline
      phosphatase in neurons pretreated with the phosphatase inhibitor okadaic acid.
      Studies with anti-HNE antibodies showed that HNE binds directly to tau, and that
      HNE immunoreactivity localizes to cell bodies and axons, cell compartments that
      contain tau. These data suggest a role for HNE in altered tau phosphorylation and
      neurofibrillary degeneration in AD.

PMID- 9243626
TI  - Circadian change of dopaminergic neuron activity: effects of constant light and
      melatonin.
AB  - Twenty-four hour profiles of tuberoinfundibular (TI), nigrostriatal and
      mesolimbic dopaminergic (DA) neuronal activities were assessed in estrogen-primed
      ovariectomized rats using DOPAC and DOPA levels in terminal regions of DA
      neurons. Significant decreases in DOPAC and DOPA levels in the median eminence
      were observed at 17.00 and 21.00 h, which corresponded with higher serum
      prolactin levels. DOPAC or DOPA levels in the striatum and nucleus accumbens
      were, however, significantly higher during the dark (21.00-05.00 h) phase. In
      rats kept under conditions of continuous light, no late afternoon decline in
      median eminence DOPA was observed; this decline could be reinstated by repeated
      injections of melatonin between 18.00 and 01.30 h for 3 days. In summary,
      circadian rhythms of central DA neurons were shown and melatonin may play an
      entraining role.

PMID- 9243627
TI  - Vasopressin and oxytocin receptor mRNAs are expressed in the rat inner ear.
AB  - The cause of endolymphatic hydrops, a characteristic finding in Meniere's
      disease, is not known. To study the possible involvement of the neurohormones
      vasopressin and oxytocin in this condition, we investigated whether transcripts
      of the genes encoding the arginine vasopressin (AVP) and oxytocin receptors are
      expressed in the rat inner ear. Utilizing the reverse transcription-polymerase
      chain reaction (RT-PCR) method, primers specific for each receptor showed a
      single message band of the expected size in the rat inner ear. When the PCR
      products were cloned, the sequences were identical to those of the real-type (V2)
      AVP receptor and oxytocin receptor transcripts. The finding of vasopressin and
      oxytocin receptor mRNAs in the inner ear suggests that these neurohypophyseal
      hormones may have roles in the regulation of inner ear fluid. In particular, the
      presence of vasopressin receptor mRNA in the inner ear supports the hypothesis of
      a relationship between high plasma vasopressin levels and endolymphatic hydrops.

PMID- 9243628
TI  - A non-invasive transport system for GDNF across the blood-brain barrier.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophin which
      supports midbrain dopaminergic neurons and spinal cord motorneurons. GDNF has
      been proposed as a possible therapeutic agent for Parkinson's disease, spinal
      cord injury or motorneuron degenerative disorders. Administration of GDNF is
      complicated by its poor penetration across the blood-brain barrier (BBB). Central
      nervous system capillaries are uniquely enriched in transferrin receptors and
      antibodies to these receptors (OX-26) have been proposed as potential carriers to
      transport large molecules across the BBB. Intravenous administration of an OX-26
      GDNF conjugate enhanced survival of spinal cord motorneurons in intraocular
      transplants, which possess an organotypic BBB. This suggests that the OX-26-GDNF
      conjugate could be utilized for non-invasive treatment of neurodegenerative
      diseases of the spinal cord or midbrain dopaminergic neurons.

PMID- 9243629
TI  - Time course of mossy fiber sprouting following bilateral transection of the
      fimbria/fornix.
AB  - Lesions of the fimbria/fornix (FF) lead to a variety of epileptiform changes in
      hippocampal activity. In epilepsy, as well as in several experimental
      preparations of epilepsy, aberrant sprouting of the dentate gyrus mossy fibers
      (MF) is observed and has been hypothesized to play a critical role in the
      generation of seizure activity. We therefore sought to determine whether MF
      sprouting also follows FF transections. FF transections did indeed lead to MF
      sprouting, which became apparent at 14 days and reached asymptotic levels at 28
      days post-lesion. These results indicate a possible mechanism for the
      epileptiform activity seen following FF lesions and provide an additional example
      of the diverse epileptogenic treatments that are accompanied by MF sprouting.

PMID- 9243630
TI  - Central effect of melatonin against stress-induced gastric ulcers in rats.
AB  - We investigated the role of melatonin in the induction of gastric lesions induced
      by water immersion restraint stress or centrally administered thyrotropin
      releasing hormone (TRH). Melatonin (0.1-1 ng) injected intracisternally (i.c) 30
      min prior to stress dose-dependently inhibited the induction of gastric lesions
      by water immersion restraint stress, while 100 micrograms/kg, i.p. failed to
      protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.)
      significantly reduced (83%) the severity of gastric lesions induced by a TRH
      analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after
      administration of 1 ng melatonin i.c. did not differ from those of rats receiving
      i.c. vehicle. These results suggest that melatonin plays a protective, anti
      stress, role in the gastric mucosa via a mechanism involving the central nervous
      system.

PMID- 9243631
TI  - Segregated distribution of TH-immunoreactivity in olfactory glomeruli.
AB  - Atypical and typical olfactory glomeruli differ in their primary afferents,
      centrifugal control and in some chemically identified subpopulations of
      interneurones. The distribution of tyrosine hydroxylase (TH)-immunopositive
      neurones in the periglomerular region of both typical and atypical glomeruli has
      been studied using a double histochemical-immunohistochemical method. A
      segregated distribution of TH-immunopositive cells was found among both types of
      glomeruli. TH-immunolabelled cells were more abundant (p < 0.05) in the atypical
      glomeruli. These data suggest that some neuronal subpopulations are related to
      specific properties of the glomerular physiology and they have a segregated
      distribution in different subsets of glomeruli. Thus, catecholamines might be
      involved in the processing of specific olfactory cues in atypical glomeruli. This
      study presents new differences in the cellular composition of typical and
      atypical glomeruli.

PMID- 9243632
TI  - Prepro-neuropeptide Y mRNA and NPY binding sites in human inferior vagal ganglia.
AB  - The inferior vagal ganglia contain the cell bodies of centrally projecting vagal
      afferent neurones. Using in situ hybridization-histochemistry with a combination
      of two antisense neuropeptide Y (NPY) oligonucleotides, we have demonstrated that
      a population of human inferior vagal perikarya express mRNA encoding prepro-NPY,
      the precursor of NPY. In vitro receptor autoradiography, using both [125I]Bolton
      Hunter-NPY ([125I]BH-NPY, 15 pM) and [125I]peptide YY ([125I]PYY, 25 pM), enabled
      visualization of NPY binding sites. Competition binding with NPY (1 microM), PYY
      (1 microM) and [Leu31,Pro34]NPY (100 nM), suggest that both Y1 and Y2 receptor
      subtypes are present on human vagal afferent neurones. These observations suggest
      a potential role for NPY in neuromodulation of vagal transmission in humans.

PMID- 9243633
TI  - Co-expression of APP with cNOS but not iNOS after cortical injury in rat.
AB  - Alterations in the expression of both the beta-amyloid precursor protein (APP)
      and nitric oxide synthase (NOS) might be involved in neurodegenerative conditions
      and/or in the neuronal response to injury. We have investigated the relationship
      between the increased expression of beta-amyloid precursor protein (APP) and the
      reactive changes in the expression of isoforms of nitric oxide synthase (NOS) in
      neurons and glial cells after small electrolytic lesions placed to the cerebral
      cortex. An increase in the expression of APP in both neurons and glial cells was
      detected 4 days post-operation. The inducible NOS (iNOS) was observed in
      macrophages or glial cells surrounding the lesion site. No major changes in
      constitutive NOS (cNOS) were found. APP immunoreactivity was not co-localized
      with either iNOS or cNOS at this survival time. At longer survival times (8 and
      12 days post-lesion), a reactive increase in the expression of cNOS in cortical
      pyramidal neurons was seen in addition to the elevated expression of iNOS in
      astrocytes. The reactive expression of cNOS was confined to a subset of neurons
      also showing a high expression of APP. The present results suggest a relationship
      between reactive changes in the expression of APP and cNOS during the neuronal
      response to injury.

PMID- 9243635
TI  - NGF has opposing effects on Na+ channel III and SNS gene expression in spinal
      sensory neurons.
AB  - Following sciatic nerve transection, the expression of sodium channel III (alpha
      III) transcripts increases and SNS (alpha-SNS) transcripts decreases in small (<
      25 microns diameter) dorsal root ganglion (DRG) neurons, which may reflect an
      interruption of retrograde transport of peripherally derived factor(s) involved
      in the regulation of these channels. To test the hypothesis that the neurotrophin
      nerve growth factor (NGF), which is abundant in peripheral targets, participates
      in the modulation of the expression of these sodium channel transcripts, we
      examined the hybridization signal of alpha-SNS and alpha-III mRNAs in small DRG
      neurons from adult rats that had been dissociated and maintained for 7 days in
      the absence or presence of exogenous NGF. Neurons maintained in control (no added
      NGF) cultures showed changes in alpha-III and alpha-SNS hybridization signal
      similar to those induced by axotomy, with increased alpha-III mRNA levels and
      decreased alpha-SNS mRNA levels, compared with those observed in small DRG
      neurons at 1 day in vitro. The addition of exogenous NGF to DRG cultures
      attenuated these alterations in transcript levels, decreasing alpha-III mRNA and
      increasing alpha-SNS mRNA expression. These results suggest that NGF participates
      in the regulation of membrane excitability in small DRG neurons by pathways that
      include opposing effects on different sodium channel genes.

PMID- 9243634
TI  - Neonatal capsaicin treatment abolishes formalin-induced spinal PGE2 release.
AB  - We investigated the effect of neonatal capsaicin treatment on formalin-evoked
      pain behavior and spinal levels of nociceptive neuromodulators using in vivo
      intrathecal microdialysis in conscious adult rats and age-matched controls.
      Capsaicin-treated rats displayed thermal hypoalgesia and a significant decrease
      in tissue content of calcitonin gene-related peptide. Paw swelling, flinching and
      release of spinal prostaglandin E2 induced by injection of formalin into the
      hindpaw were also reduced in capsaicin-treated rats compared with controls,
      whereas glutamate, aspartate and taurine release was unaffected. These data
      suggest that formalin-induced inflammation, pain behavior and spinal
      prostaglandin E2 release are mediated by mechanisms sensitive to neonatal
      capsaicin while the formalin-evoked release of amino acids in the spinal cord is
      not.

PMID- 9243636
TI  - Photoperiod-temperature and neuroblast proliferation-migration in the adult
      lizard cortex.
AB  - The lizard medial cortex (a zone homologous to the mammalian fascia dentata)
      shows delayed postnatal neurogenesis throughout the lifetime of these animals.
      Experimental lesioning of this area is followed by neuronal regeneration, a
      unique phenomenon in the adult amniote telencephalon. The differential effects of
      temperature and photoperiod on postnatal neurogenetic activity were studied using
      tritiated thymidine pulses and posterior autoradiography as well as proliferating
      cell nuclear antigen (PCNA) immunostaining. Long (summer) photoperiods increased
      the number of proliferating neuroblasts in the ependymal neuroepithelium. Cold
      (winter) temperature prevented migration of the newly generated immature
      neurones.

PMID- 9243637
TI  - Selective localization of mouse aldehyde oxidase mRNA in the choroid plexus and
      motor neurons.
AB  - Aldehyde oxidase (AO), a protein involved in the catabolism of catecholamines, is
      the product of a gene potentially responsible for one of the familial forms of
      the motor neuron disease, amyotrophic lateral sclerosis (ALS). Here, we report on
      the cloning of a partial cDNA coding for the mouse enzyme. Using this cDNA as a
      probe, we demonstrate that the AO transcript is expressed in the epithelial
      component of the choroid plexus. More importantly, in the gray matter, the mRNA
      is selectively localized in the large motor neurons of the nuclei of facial,
      motor trigemini and hypoglossus nerves and in the motor neurons of the anterior
      horns of the spinal cord. This localization is consistent with a possible role of
      AO in the pathogenesis of ALS.

PMID- 9243638
TI  - c-fos expression in the trigeminal sensory complex and pontine parabrachial areas
      following experimental tooth movement.
AB  - Ortodontic tooth movement causes continuous pain. However, it does not appear
      immediately, usually appearing after the application of orthodontic force to the
      teeth. Mechanically induced inflammatory responses in the periodontal membrane
      are assumed to be related to the mechanism of the later pain sensation. In the
      present study, we investigated Fos-like immunoreactivity in the trigeminal
      sensory complex and pontine parabrachial areas 24 h after the commencement of
      experimental tooth movement. An orthodontic elastic module was unilaterally
      inserted between upper molars. Following experimental tooth movement, Fos-like
      immunoreactive neurons appeared ipsilaterally in the trigeminal subnucleus
      caudalis and bilaterally in the lateral parabrachial nucleus. These results
      indicate that experimental tooth movement evokes delayed and continuous
      nociception after application of orthodontic force to the teeth and that the
      nociceptive information would be conveyed to the ipsilateral trigeminal
      subnucleus caudalis and further processed, at least in part, to the lateral
      parabrachial nucleus.

PMID- 9243640
TI  - Role of Gq alpha in insulin-stimulated glucose uptake by C6 glioma cells.
AB  - To investigate the possibility that insulin-stimulated glucose uptake in C6 cells
      is due to transactivation of a G protein-mediated pathway, the role of Gq alpha
      in insulin signaling was studied. Insulin stimulation of [3H]2-deoxy-D-glucose
      (2DG) uptake by C6 cells was time- and concentration-dependent: at a
      concentration of 1 microM, insulin stimulated 2DG uptake by C6 cells by about 30%
      (p < 0.05). Pertussis toxin treatment of C6 cells did not alter the ability of
      insulin (1 microM) to promote 2DG uptake, ruling out the involvement of Gion in
      insulin-stimulated hexose uptake. Next, C6 cells were transfected with Gq alpha
      cDNA for 48 h, challenged with 1 microM insulin, and 2DG uptake by the cells was
      determined. Insulin-stimulated 2DG uptake was 1.14 +/- 0.03 and 1.75 +/- 0.19
      nmol/min/mg protein in mock- and Gq alpha-transfected cells, respectively (p <
      0.05); insulin stimulated 2DG uptake in Gq alpha-transfected cells by 54%. These
      results suggest an involvement of Gq alpha in the transactivation of the G
      protein signal transduction pathway by insulin.

PMID- 9243641
TI  - Glutamate uptake is inhibited by L-arginine in mitochondria isolated from rat
      cerebrum.
AB  - Uptake of L-[14C]glutamate (L-[14C]GLU) into nonsynaptic mitochondria isolated
      from rat cerebral hemispheres was measured in the presence of potential
      modulators of amino acid transport. The L-GLU carrier agonist 0.2 mM L-aspartate
      (L-ASP) virtually abolished L-GLU uptake (ASP/GLU concentration ratio, 1:1). L
      Arginine (L-ARG) inhibited L-GLU uptake in a dose dependent manner over the
      concentration range 0.1-5 mM to maximum inhibition of 85%. Putrescine or ammonia
      had no effect, whereas 5 mM creatine and the NO generator, 5 mM sodium
      nitroprusside, increased the uptake by 73% and 57%, respectively. D-ARG was three
      times less effective in inhibiting L-GLU uptake than L-ARG at 5 mM concentration.
      The L-amino acids ornithine, lysine, histidine, tyrosine, phenylalanine, proline,
      leucine, isoleucine, tryptophan, glycine, methionine, valine, serine, taurine,
      alanine or cysteine did not affect the uptake when added in concentrations of 2-5
      mM. A 14% inhibition of L-GLU uptake was noted in the presence of L-glutamine (L
      GLN) (2 mM) or a dicarboxylate carrier ligand, alpha-ketoglutarate (alpha-KG) (5
      mM), and a 30% inhibition with a dicarboxylate carrier inhibitor phenylsuccinate
      (PhSc) (5 mM). The results suggest that L-ARG functions as a specific endogenous
      modulator of cerebral mitochondrial L-GLU transport.

PMID- 9243639
TI  - DC-Chol liposome-mediated gene transfer in rat spinal cord.
AB  - We examined the potential of non-viral vector-mediated gene transfection in the
      rat spinal cord. Reporter gene (beta-gal) or brain-derived neurotrophic factor
      (BDNF) cDNA containing a pCMV promoter complexed with DC-Chol liposomes was
      injected into the intact rat spinal cord gray matter. RT-PCR confirmed the
      increased expression of BDNF mRNA in the injection areas. X-gal staining
      demonstrated the localized expression of beta-gal reporter genes. No overt tissue
      damage caused by DC-Chol liposome/DNA complex injections was detected. These
      results suggest that cationic liposome-mediated delivery can be a practical
      method for gene transfer in spinal cord.

PMID- 9243642
TI  - cAMP decreases steady-state levels of delta-opioid receptor mRNA in NG108-15
      cells.
AB  - We have compared several drug combinations for their ability to increase basal
      cAMP and to down-regulate delta-opioid receptor mRNA levels. Continuous treatment
      for up to 48 h with a phosphodiesterase inhibitor in combination with the
      adenylyl cyclase activator forskolin showed an early peak response, but cAMP
      levels returned to control after 8 and 24 h. Increases in cAMP level up to 150
      fold were observed after treatment for 1 h with a series of drugs (rolipram,
      IBMX/forskolin, rolipram/forskolin, dibutyryl cAMP, and prostaglandin E2) that
      increase cAMP by different mechanisms. A significant decrease in DOR mRNA level,
      to 31% of control, followed the three treatments that produced the largest
      increases in cAMP level: IBMX/forskolin, rolipram/forskolin, and prostaglandin
      E2.

PMID- 9243643
TI  - D3 receptor test in vitro predicts decreased cocaine self-administration in rats.
AB  - The three dopamine agonists with highest reported D3 receptor selectivity in
      vitro, pramipexole, quinelorane and PD128,907, decreased self-administration of a
      high dose of cocaine in rats as a result of a leftward shift in the cocaine dose
      effect function. In contrast the D3 preferring antagonist nafadotride increased
      cocaine self-administration. Moreover the relative potencies of these and other
      D2-like dopamine agonists (lisuride, 7-OH-DPAT, quinpirole, apomorphine,
      bromocriptine) to modulate cocaine self-administration were highly correlated
      with their relative potencies for increasing mitogenesis in vitro in cell lines
      expressing D3 but not D2 receptors. These results support the hypothesis that the
      D3 receptor may be an important target for pharmacotherapies for cocaine abuse
      and dependence.

PMID- 9243644
TI  - Cortical processing mechanism for vocalization with auditory verbal feedback.
AB  - To investigate the relationship between motor and sensory speech center, cortical
      activity was examined using PET while normal subjects perceived their own voice
      which sounded different to the articulated one. The results showed significant
      activation in the superior temporal gyri with absence of activity in the
      supplementary motor area (SMA). In a previous study we found significant
      activation in SMA with no activity in the superior temporal gyrus when normal
      subjects simply vocalized. Thus, two different cortical pathways for vocalization
      were delineated: programmed pathway in SMA, and pathway with auditory verbal
      feedback. The former is thought to be the mature system in the adult, and the
      latter may be related to speech acquisition.

PMID- 9243645
TI  - Dystrophins in developing retina: Dp260 expression correlates with synaptic
      maturation.
AB  - Dystrophin, the protein altered in Duchenne muscular dystrophy (DMD), is
      necessary for normal retinal function and exists in several isoforms. We examined
      the expression of dystrophin and utrophin proteins and transcripts in the rat
      retina at different developmental stages using Western blots and semi
      quantitative RT-PCR. Our results revealed the presence of utrophin (DRP1), G
      utrophin and/or DRP2 and four dystrophin isoforms (Dp427, Dp260, Dp140, Dp71) in
      the normal adult rat retina. Only Dp260 showed a marked progressive increase with
      age at both protein and mRNA levels. This variation is consistent with the
      establishment of synaptic functions in the developing retina and suggests a key
      role for this apo-dystrophin in synaptogenesis.

PMID- 9243646
TI  - Real-time monitoring of the effects of normothermia and hypothermia on
      extracellular glutamate re-uptake in the rat following global brain ischemia.
AB  - Brain hypothermia during ischemia may have a neuroprotective effect on
      pathological and functional outcomes in vivo. Although a microdialysis study
      demonstrated that hypothermia decreases glutamate release into the extracellular
      space, the issue of whether this suppression of the glutamate elevation normally
      accompanying ischemia is attributable to inhibition of intra-ischemic release or
      acceleration of post-ischemic re-uptake was not addressed. Recently, we
      established a real-time method for monitoring glutamate levels in extracellular
      space, utilizing a dialysis electrode. This method allows detailed analysis of
      the in vivo dynamics of biphasic glutamate elevation in the extracellular space
      during the intra-ischemic period and post-ischemic re-uptake. The present results
      show that post-ischemic hypothermia has little effect on the initial glutamate
      release, but remarkably enhances post-ischemic glutamate re-uptake.

PMID- 9243647
TI  - The role of the temporal coding system in the auditory cortex on speech
      recognition.
AB  - To elucidate the temporal coding system for speech recognition, we synthesized
      stimulation sounds which do not contain formant information but do contain
      temporal information by transforming original sound wave to click sequences.
      Using this stimulation sound, we performed a recognition test and used PET to
      examine the cortical activities in normal subjects listening to this sound. The
      results of the recognition test showed a good perception of the sounds made from
      sequential speech. The PET study demonstrated significant activation of the
      superior temporal gyri while listening to the stimulation speech sounds. Our
      results imply that these stimulation sounds were processed semantically in the
      auditory cortices. The temporal processing system is thought to make an important
      contribution to speech recognition.

PMID- 9243648
TI  - Differential expression of the GABAA receptor alpha 1 subunit in developing
      chicken brain.
AB  - A unique segment of chicken GABAA receptor alpha 1 subunit was expressed in E.
      coli and used to generate an antiserum 2A specific for the subunit. The DNA
      fragment encoding the segment of alpha 1 was obtained by selective amplification
      by polymerase chain reaction (PCR) from a chicken brain cDNA library. The
      antiserum is characterized by its capacity to immunoprecipitate a
      [3H]flunitrazepam binding protein of 50 kDa, the chicken GABAA receptor alpha 1
      subunit. Subsequent immunoblotting and immunocytochemistry analyses reveal that
      alpha 1 is expressed in the optic tectum and cerebellum as early as embryonic day
      15 (E15), in various areas of telencephalon as early as E20 and distributed
      heterogeneously among different cell types. The early expression of alpha 1 may
      imply its functional significance in neurotransmission.

PMID- 9243649
TI  - Scrapie-induced neuron loss is reduced by treatment with basic fibroblast growth
      factor.
AB  - Neuron loss can be a prominent feature of the pathology of transmissible
      spongiform encephalopathies (TSEs); recent evidence indicates that this loss
      occurs through apoptosis. Growth factor treatment of other neurodegenerative
      diseases has been shown to protect neurons destined for apoptosis, and several
      types of experimental retinopathy have been successfully treated with basic
      fibroblast growth factor (bFGF). In a murine scrapie model which develops a
      severe loss of photoreceptors, we administered a single intravitreal injection of
      bFGF four-fifths of the way through the disease process; this doubled the number
      of photoreceptors surviving for up to 5 weeks, i.e. to the terminal stages of the
      disease. This is the first time that a potential late-stage therapy for the TSEs
      has been demonstrated.

PMID- 9243650
TI  - Prevalence of glaucoma in Ponza, Italy: a comparison with other studies.
AB  - The purpose of this study was to determine the prevalence of glaucoma in Ponza,
      Italy. The design was a population-based prevalence survey of residents of Ponza
      aged 40 years or older. There were 1,296 official residents identified by a house
      to-house census, of whom 1,226 were identified as eligible for the study. Of
      these, 1,034 individuals (449 males and 585 females), or 84.3% of the eligible
      population, participated in the ophthalmological examination. A two-stage method
      was adopted to identify cases of glaucoma. All subjects underwent a standardized
      initial examination. Glaucoma suspects and 50% of non-suspects were referred to a
      definitive examination which included visual field testing. Patients were defined
      as glaucoma cases if they presented abnormal visual fields and at least one of
      the following: high 10P, large or asymmetric cup-to-disc ratio. In addition to
      typical glaucomatous visual field defects such as paracentral scotoma, nasal
      step, arcuate scotoma and temporal and/or central islands fields, a visual field
      defect was identified as a decrease in sensitivity greater than 6 db in at least
      one location of the central 10 degrees, two locations of the central 20 degrees
      or three locations of the central 30 degrees. Prevalence rates of 2.51% of
      Primary Open Angle Glaucoma (1.72%-3.66%, CI 95%), 0.97% of Primary Closed Angle
      Glaucoma (0.53%-1.77%, CI 95%) and 0.29% of secondary glaucoma were found.
      Moreover, 2.13% of probable POAG (1.41%-3.20%, CI 95%) and 6.00% of High
      Intraocular Pressure (4.71%-7.61%, CI 95%) were found. The prevalence rates of
      POAG found in the Ponza Ophthalmological Survey are consistent with the results
      of other studies. Minor differences are most likely due to the different criteria
      adopted in the assessment of glaucomatous visual field damage.

PMID- 9243651
TI  - A comparison of participants with non-participants in a population-based
      epidemiologic study: the Melbourne Visual Impairment Project.
AB  - PURPOSE: Adequate participation in population-based studies in essential to
      ensure that the sample is representative of the population under investigation.
      Participants may differ from non-participants on important variables such as age,
      sex socioeconomic status, and general health factors. The Melbourne Visual
      Impairment Project (Melbourne VIP) is a population-based study designed to
      increase understanding of the prevalence and severity of common ocular disorders
      affecting people 40 years of age and over. AIM: The aim of this study was to
      determine the potential for any non-response bias by comparing data from
      participants and non-participants of the Melbourne VIP. METHODS: Specific
      demographic and general variables were compared between the two groups. The
      variables included age, sex, education level, and social status. The reason for
      non-attendance was also recorded. RESULTS: A total of 3271 (83%) eligible
      residents from the 9 sample areas were screened; 46% males and 54% females.
      Language spoken at home was significantly associated with participation.
      Residents whose main language at home was not English were less likely to attend
      the screening centre. (OR: 0.60; CI: 0.44-0.81). The main reasons given for non
      attendance by eligible residents were lack of interest (6%), too busy to attend
      (4%), personal illness (2%), and attend own eye specialist (2%). CONCLUSION: We
      believe these results will not impact significantly on the interpretation of
      gender and age-specific data from the Melbourne VIP.

PMID- 9243652
TI  - Absence of a relationship between malnutrition and trachoma in preschool
      children.
AB  - PURPOSE: To determine if there is an association between malnutrition and
      clinical trachoma among children in a trachoma endemic region of Tanzania.
      METHODS: 189 children age one to five were examined by a trained eye nurse for
      the presence of active trachoma, using the WHO simplified grading scheme. One
      examiner also measured the arm circumference of the mid-aspect of the upper left
      arm on the same children. Trachoma was defined as the presence of follicular
      trachoma (TF) and/or severe trachoma (TI). Malnutrition was defined two ways: a
      mid-arm circumference of less than 12.5 cm, and a value one standard deviation
      below the age-specific mean. RESULTS: Overall, 57% of children had trachoma, and
      9% had severe trachoma. The percentage of children with arm circumference below
      12.5 cm varied with age from 96% in the one-year-olds to 35% in the six-year
      olds. Using either method of classifying malnutrition, there was no association
      with trachoma, nor with severe trachoma. CONCLUSION: Trachoma and malnutrition
      are both common in this sample of children, although no relationship between the
      two was observed. Further work on the nutritional status in those with
      subclinical infection may be warranted.

PMID- 9243653
TI  - Racial variations in treatment for glaucoma and cataract among Medicare
      recipients.
AB  - PURPOSE: To identify the location of barriers to treatment for glaucoma and
      cataract among African-American Medicare beneficiaries. METHODS: We examined the
      receipt of eye care in general and care for glaucoma and cataract in particular
      among black and white Medicare beneficiaries using 1991 Medicare physician claims
      data. Racial differences in treatment for glaucoma and cataract were examined
      both for the Medicare population as a whole and for identified eye care users.
      The results were compared to the expected value of black-white difference based
      on population prevalence data for each specific condition. RESULTS: Thirty
      percent of black beneficiaries and 45% of white Medicare beneficiaries used eye
      care services in 1991. After adjusting for the expected difference in prevalence,
      black beneficiaries were half as likely to be surgically treated for glaucoma
      compared to white beneficiaries, and 80% as likely for cataract. When the
      analysis was restricted to those using eye care services, blacks continued to
      have lower than expected rates of treatment for glaucoma (observed RR = 3.2, 95%
      confidence interval = 3.1-3.4 vs an expected RR of 4.3, 95% confidence interval =
      3.5-5.4), but a higher rate of treatment for cataract (RR = 1.2, 95% confidence
      interval = 1.2-1.3). Among those with physician-diagnosed glaucoma and cataract,
      blacks were more likely to undergo surgical treatment for these conditions than
      whites (RR = 1.5 for glaucoma, 95% confidence interval = 1.4-1.5; RR = 1.2 for
      cataract, 95% confidence interval = 1.2-1.3). CONCLUSION: Barriers to treatment
      for glaucoma and cataract among black Medicare beneficiaries involve primarily
      limitations in access to the eye care system. The undertreatment for glaucoma
      among black beneficiaries was reduced, but not eliminated, after removing the
      effect of unequal access to the eye care system.

PMID- 9243654
TI  - Effects of randomizing second eyes in a trial to evaluate preoperative medical
      testing for cataract surgery.
AB  - The statistical and practical implications of including second eye surgeries were
      examined in a clinical trial designed to evaluate the impact of routine
      preoperative testing prior to cataract surgery on major medical events occurring
      within seven days following surgery. In order to detect a 0.8% difference in the
      rates of rare major medical events between the tested and untested groups, 20,000
      surgeries must be randomized. About 30% of cataract operations were estimated to
      be done on second eyes of patients already included in the cohort. Different
      options for dealing with second eye surgeries were: (1) exclusion of all second
      eye surgeries, (2) inclusion of second eye surgeries only if the first eye is not
      enrolled, (3) inclusion of first and second eyes but randomization of patients
      rather than eyes, and (4) inclusion of first and second eyes but randomization of
      surgeries rather than patients. The final decision was to exclude second eye
      surgeries done within 28 days of first eye surgeries, but to rerandomize all
      other second eye surgeries. Differences in event rates between treatment groups
      can be estimated using Generalized Estimating Equations, and the association
      between outcomes of first and second eye operations estimated with pairwise odds
      ratios. An anticipated small positive correlation is likely to have minimal
      impact on statistical power and effective sample size.

PMID- 9243655
TI  - Ocular health myths among a hospital staff.
AB  - In order to evaluate their common beliefs in the field of ocular health, an
      exploratory survey was carried out among 122 professionals belonging to different
      ranks and specialty areas of the University of Campinas Clinical Hospital
      (UNICAMP-CH), Sao Paulo, Brazil. The non-structured questionnaire used asked
      about common ophthalmologic problems as well as the presence of popular myths
      about ocular health, such as: 'cure' of visual problems by the use of glasses;
      reading under insufficient lighting or watching TV too much close to the
      apparatus is harmful; consequences from the intensive use of the eyes; or special
      food being needed for better vision. The results indicated the existence of
      various misconceptions, even among health professionals, such as: belief in the
      cure of refractive problems by the use of glasses (40.0%); or damage to vision
      due to insufficient lighting, watching TV too much close to the apparatus or from
      the intensive use of the eyes (86.7%). Among the professionals performing
      activities within the ophthalmology department, 62.5% admitted believing in
      visual damage as a result of conditions such as those mentioned above and 37.5%
      stated that reading in a moving vehicle is detrimental to vision. From these
      data, one is entitled to conclude that misconceptions continue to be present,
      even among professionals in the health area; this indicates that educational
      programs in ocular health should be provided, especially for individuals working
      within a hospital ophthalmological service.

PMID- 9243656
TI  - Comparative results of combined procedures for glaucoma and cataract: I.
      Extracapsular cataract extraction versus phacoemulsification and foldable versus
      rigid intraocular lenses.
AB  - BACKGROUND AND OBJECTIVES: The refinements of small-incision cataract surgery by
      phacoemulsification with foldable intraocular lens (IOL) implantation have
      recently permitted new options for combined trabeculectomy with cataract
      extraction. The objectives of this study were to compare the long-term
      intraocular pressure (IOP) control and visual outcome between trabeculectomies
      combined with extracapsular cataract extraction (ECCE) versus those with
      phacoemulsification, and to analyze these same factors for foldable versus rigid
      IOLs. PATIENTS AND METHODS: The authors retrospectively reviewed the charts of
      311 patients (397 eyes) who underwent combined trabeculectomy with cataract
      extraction and posterior chamber IOL implantation. In all of the surgeries,
      releasable scleral flap sutures were used. The mean follow-up was 22.9 +/- 15.1
      months, with a minimum follow-up of 12 months. RESULTS: Trabeculectomy combined
      with phacoemulsification had a lower postoperative complication rate and was more
      effective than trabeculectomy combined with ECCE in reducing IOP to less than 20
      mm Hg with or without medication (95% vs 82%) and in improving vision to levels
      of 20/40 or better (71% vs 52%) (P < .001). Regarding IOLs, foldable silicone
      lenses were found to be an effective alternative to polymethylmethacrylate lenses
      in combined surgeries in terms of a controlled IOP of less than 20 mm Hg (97% vs
      97%) and visual recovery to 20/40 or better (78% vs 63%). CONCLUSION: The
      combination of trabeculectomy with releasable scleral flap sutures and small
      incision cataract surgery with foldable IOL implantation has improved
      postoperative IOP control and visual rehabilitation.

PMID- 9243657
TI  - Comparative results of combined procedures for glaucoma and cataract: II. Limbus
      based versus fornix-based conjunctival flaps.
AB  - BACKGROUND AND OBJECTIVE: One of the variables to be considered in a combined
      procedure for glaucoma and cataract is the type of conjunctival flap to be used.
      The objective of this study was to compare the effects of limbus-based and fornix
      based conjunctival flaps on postoperative long-term intraocular pressure (IOP)
      control and visual acuity after combined trabeculectomy with phacoemulsification.
      PATIENTS AND METHODS: The authors retrospectively reviewed the charts of 189
      patients (215 eyes) who underwent combined trabeculectomy with
      phacoemulsification, posterior chamber intraocular lens (IOL) implantation, and
      intraoperative mitomycin-C administration and who had a minimum follow-up of 12
      months. The results of the limbus-based (151 eyes) versus fornix-based (64 eyes)
      conjunctival incisions used in these combined procedures were compared. RESULTS:
      In the limbus-based conjunctival flap group, 146 eyes (97%) achieved an IOP of
      less than 20 mm Hg, with or without medication; 62 eyes (97%) of the fornix-based
      conjunctival flap group (P > .05) achieved this result. A visual acuity of 20/40
      or better was noted in 106 eyes (70%) in the limbus-based conjunctival flap group
      and in 45 eyes (70%) in the fornix-based conjunctival flap group (P > .05) at the
      last examination. Early wound leakage was observed more frequently in the fornix
      based conjunctival flap group (8% vs 1%) (P = .014); however, it was not a
      serious clinical problem, as only 1 eye required surgical repair. Posterior
      capsular opacification was found more often in the limbus-based conjunctival flap
      group (25% vs 14%) (P = .072) and required more frequent laser capsulotomy (22%
      vs 9%) (P = 0.03). CONCLUSION: Limbus-based and fornix-based conjunctival flaps
      appear to be comparable with respect to postoperative IOP control and visual
      acuity after a combined trabeculectomy with phacoemulsification and posterior
      chamber IOL implantation in cases supplemented by intraoperative mitomycin-C.

PMID- 9243658
TI  - Phacoemulsification for cataract following pars plana vitrectomy.
AB  - BACKGROUND AND OBJECTIVE: To determine if the technical aspects of
      phacoemulsification for removal of cataract following pars plana vitrectomy
      differ from those of phacoemulsification for removal of cataract in
      nonvitrectomized eyes. PATIENTS AND METHODS: Twenty-two eyes that had undergone
      prior vitrectomy were identified through a retrospective review of chart notes
      and operative records of 1039 consecutive cataract extractions performed by one
      surgeon. RESULTS: Complications of proliferative diabetic retinopathy was the
      most common indication for prior vitrectomy. The predominant lens change was
      nuclear sclerosis. Deep anterior chambers with large anterior to posterior
      excursions of the iris lens diaphragm with simultaneous fluctuation in pupil size
      occurred during phacoemulsification. The posterior capsule was flaccid and mobile
      during lens cortex removal. No posterior capsules ruptured. Postoperative visual
      acuity improved in 91% of the patients. CONCLUSIONS: Prior vitrectomy was
      associated with diabetes and nuclear sclerotic cataract. Phacoemulsification in
      this patient population was associated with inadequate pupillary mydriasis,
      superior conjunctival scarring, intraoperative anterior chamber depth, pupil
      size, and iris lens excursions that hindered phacoemulsification tip placement.
      Posterior capsules were excessively flaccid, prone to rapid anterior and
      posterior excursions, and may have plaques that are resistant to intraoperative
      removal.

PMID- 9243659
TI  - Ultrasound-guided cryotherapy for retinal tears in patients with vitreous
      hemorrhage.
AB  - BACKGROUND AND OBJECTIVE: The goal was to utilize ultrasound-guided cryotherapy
      as an immediate, low-risk, noninvasive, precise method of treating retinal tears
      obscured by vitreous hemorrhage. PATIENTS AND METHODS: Eleven patients with
      sudden onset of vitreous hemorrhage were referred for diagnosis and management.
      Ophthalmoscopy with scleral depression was unsuccessful at localizing peripheral
      retinal tears, and all of the patients were examined with ultrasound using the
      techniques of standardized echography. The cryoprobe was positioned for
      cryotherapy using both transverse and longitudinal B-scan approaches following
      the indentation of the globe as it appeared on the oscilloscope. RESULTS: On
      follow-up examination after the vitreous hemorrhage cleared, 10 of the 11 tears
      were examined by ophthalmoscopy and were thought to have been adequately treated.
      One patient had a retinal detachment after remaining stable for 3 months. Two
      patients were treated with laser to enhance the cryotherapy seal. One patient was
      observed by another physician and underwent vitrectomy due to vitreous hemorrhage
      that persisted 2 months following cryotherapy. After vitrectomy, the physician
      reported a successful cryotherapy reaction at the treated tear. One final patient
      in the series required vitrectomy and scleral buckle before the hemorrhage had
      cleared, and the treatment did not appear to be complete. CONCLUSION: Ultrasound
      guided cryotherapy provides a noninvasive, inexpensive treatment alternative for
      retinal tears obscured by vitreous hemorrhage.

PMID- 9243660
TI  - Do standard procedures in squint surgery influence the blood-aqueous barrier?
AB  - BACKGROUND AND OBJECTIVE: Surgery on the rectus muscles may interfere with
      anterior segment perfusion. This study investigates the influence of combined
      rectus muscle surgery on the blood-aqueous barrier in children. Namely, the
      influences of tucking and resection procedures were compared. PATIENTS AND
      METHODS: Laser flare measurements for tyndallometry were performed preoperatively
      and postoperatively in 25 children. Fifteen of the children had undergone a
      combination of a rectus recession and tucking; 10 had undergone a combined
      recession-resection procedure. RESULTS: The mean preoperative flare value was 4.1
      photon counts/ms versus 3.7 photon counts/ms postoperatively in the eyes that had
      undergone surgery. Statistical evaluation showed that the postoperative changes
      were insignificant. No significant difference was found between the two surgical
      techniques (tucking vs resection) regarding the preoperative versus postoperative
      flare value change (level of statistical significance .05). CONCLUSION: Combined
      squint surgery, either recession-tucking or recession-resection, was not shown to
      influence the blood-aqueous barrier.

PMID- 9243662
TI  - Free radical production by Nd:YAG laser photodisruption.
AB  - BACKGROUND AND OBJECTIVES: Plasma and cavitation bubble formation during optical
      breakdown in aqueous media may produce hydroxyl (*OH) radicals. The authors'
      objectives were to detect *OH produced by a neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser photodisruptor and to determine *OH concentration in relation to
      laser energy. MATERIALS AND METHODS: *OH was assayed by measuring absorbance of
      triiodide (I3-) in a potassium iodide (KI) solution exposed to optical breakdown
      by an Nd:YAG laser. The concentration-dependent reduction of radical production
      in relation to cystamine concentration was evaluated. RESULTS: I3- concentration
      increased linearly with total irradiation energy and decreased exponentially with
      increasing cystamine concentration. *OH concentration was calculated using
      extinction coefficients of I3- and chemical equations relating I3- formation to
      *OH. CONCLUSIONS: The authors calculated that approximately 4 x 10(-12) moles of
      *OH are produced in a typical posterior capsulotomy of 100 mJ of total energy.
      This *OH concentration could produce strand breaks in approximately 0.4% of
      vitreous hyaluronic acid molecules, but is unlikely to produce clinical effects.

PMID- 9243663
TI  - Treatment of central retinal vein occlusion.

PMID- 9243661
TI  - Photodynamic therapy for antifibrosis in a rabbit model of filtration surgery.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this pilot study was to investigate the
      use of photodynamic therapy (PDT) using tin ethyl etiopurpurin (SnET2) as an
      adjunctive antifibrotic therapy for filtering surgery in a rabbit model.
      MATERIALS AND METHODS: The pharmacokinetics of SnET2 were established by
      intravenous (1 mg/kg) and subconjunctival (25, 50, or 75 micrograms) injections
      and compared with controls. Intravenous and subconjunctival SnET2 injections were
      given prior to posterior lip sclerectomies followed by postoperative laser
      irradiation (664 +/- 7 nm; 100 mW/cm2; 30 J/cm2). Antifibrotic efficacy was
      established by clinical response and histologic examination. RESULTS: After
      subconjunctival injections, large areas of avascular conjunctiva were produced
      and filtering bleb survival was prolonged. No effect was found for intravenously
      administered photosensitizer followed by light irradiation. CONCLUSIONS: PDT may
      be an alternative antifibrotic therapy for filtration surgery that does not use
      chemotherapeutic agents or ionizing radiation. Multiple parameters (light, drug
      dose, irradiation area) may be manipulated to improve predictability of the
      antifibrotic effect.

PMID- 9243664
TI  - An unusual complication of a postcataract filtering bleb.
AB  - Inadvertent blebs are sometimes encountered after cataract surgery using sutured
      limbal incisions. A number of surgical techniques have been described in the
      planned management of such blebs. Occasionally, an intraoperative bleb rupture
      may occur. The authors describe a rotational scleral autograft technique that can
      help in the management of this complication.

PMID- 9243665
TI  - An applicator-shaped scleral depressor for vitreoretinal surgery.
AB  - This article describes an instrument that combines a standard T-shaped scleral
      depressor at one end with a cotton applicator-shaped depressor at the other end.
      The applicator-shaped depressor has a matted surface to prevent slippage. This
      simple instrument has several advantages over depressors now available for
      intraoperative use.

PMID- 9243666
TI  - A new water bath for ultrasonic biomicroscopy.
AB  - Ultrasonic biomicroscopy (UBM) has added greatly to our understanding of the
      development of certain forms of glaucoma. Methylcellulose is usually recommended
      as the appropriate coupling medium between the transducer and the eye because of
      its increased viscosity, which makes it more easily retained on the eye. A new
      water bath has been developed that fits the eye so well that saline, a superior
      coupling agent, can be substituted for methylcellulose. This new water bath is a
      flexible polysiloxane cup with a beveled inner edge, providing a watertight seal
      and thus permitting the use of saline as the coupling medium for UBM. Saline,
      because of its lack of impurities, generates images that are superior in quality
      to those produced with methylcellulose as the coupling medium.

PMID- 9243667
TI  - A disposable needle for frontalis suspension surgery in congenital ptosis.
AB  - In six patients affected by congenital ptosis, a disposable epidural anesthesia
      needle was used instead of a Wright needle for frontalis suspension surgery. For
      each of the patients in this study, the use of a disposable needle permitted
      smaller supra-brow area incisions with a minimal scar. The needle also created a
      smaller breach in the plane of levator aponeurosis and preaponeurotic fat,
      causing less tissue edema and bleeding than with a Wright needle.

PMID- 9243668
TI  - A safety suture for implantation of posterior chamber intraocular lenses in
      complicated cases.
AB  - Implantation of a posterior chamber intraocular lens can be difficult and risky
      in complicated cases such as a large tear in the posterior capsule, a cloudy
      cornea, or a small pupil. The author describes a technique for performing a safe
      implantation. The intraocular lens is supported by a suspension suture, which is
      threaded through a positioning hole or tied to the lens haptic. The suture is
      removed once a stable fixation is achieved.

PMID- 9243669
TI  - Report card on HMOs.

PMID- 9243670
TI  - The orthopedic and social outcome of open tibia fractures in children.
AB  - To determine whether the accepted principles of management of open tibia
      fractures apply to children, 40 consecutive open fractures of the tibial shaft in
      skeletally immature patients were retrospectively reviewed. Attempts were made to
      evaluate the functional and social impact of open tibia fractures in children.
      All open fractures were initially treated by rapid irrigation and debridement
      which was repeated every 48 hours until soft tissues stabilized. The average age
      was 10.1 years and average follow up was 26 months (range: 18 to 84). There were
      16 grade I, 10 grade II, and 14 grade III open fractures. The grade III fractures
      were further subdivided into 6 grade IIIA, 7 grade IIIB, and 1 grade IIIC. The
      average time to union was 7.5 and 11.0 weeks in the grade I and II fractures
      respectively, with no infections and no delayed unions. In grade III fractures,
      the average time to union was 15 weeks, with 1 infection and 3 delayed unions.
      Bone grafting using autogenous iliac crest was performed on 2 patients. The
      children surveyed missed an average of 4.1 months of school and 33% had to repeat
      a year. Twenty-five percent of the children complained of nightmares involving
      the events of the accident. Chronic pain despite solid union was found in 30% of
      patients. Forty percent of those surveyed (7 grade III fractures) complained of a
      limp. The low incidence of soft tissue complications and infections in the study
      population supports applying in children the same basic soft tissue management
      principles of open fracture treatment as used in adults. While bone stabilization
      options are limited in children, the rate of successful union without adjunctive
      bone grafting is much higher than that of adults treated under similar protocols.
      Routine early iliac crest bone grafting is unnecessary. The prevalence of gait
      abnormality despite fracture union should be taken into account during the
      patient's rehabilitation. The extensive time missed from school and resulting
      scholastic setback should not be underestimated.

PMID- 9243671
TI  - Lateral extracavitary approach to the thoracic and thoracolumbar spine.
AB  - Twenty-nine patients with anterior spinal cord compression underwent
      decompression and fusion through a laterally based approach to the thoracic and
      thoracolumbar spine. The lateral extracavitary approach allows access to the
      vertebral bodies as well as the posterior elements through a single incision.
      This approach was chosen for patients who had complicating medical conditions
      that made staged procedures less desirable. Ten men and 19 women with an average
      age of 53 years were studied. Diagnoses included post-traumatic deformity,
      metastatic disease, osteomyelitis, and primary neoplasms. Twenty-three patients
      had frank neurologic loss preoperatively, and 28 patients had significant medical
      comorbidities as evidenced by American Society of Anesthesiology classes II, III,
      and IV. One patient died postoperatively from pneumonia, which developed in a
      lung with metastatic disease, and two patients developed seromas that
      subsequently became infected. The average intensive care unit stay was less than
      2 days. Patients remained intubated for an average of 13 hours after surgery. In
      this population of medically compromised patients with difficult spinal disease,
      the lateral extracavitary approach provided an effective means of one-stage
      treatment. Patients tolerated the procedure, and cardiopulmonary complications
      were minimal. This approach is most appropriate in patients who require posterior
      stabilization in conjunction with anterior stabilization.

PMID- 9243672
TI  - A new in vivo method for the direct measurement of nutrient artery blood flow.
AB  - A new method of directly measuring nutrient artery blood flow using ultrasonic
      probes is described. These probes have provided reproducible results in our
      experiments. Advantages of ultrasonic probes include the direct measurement of
      blood flow through small arteries, ease of use, accuracy of measurement,
      applicability to a wide range of vessel diameters, the capability of chronically
      monitoring blood flow over time using permanently implanted probes, and the
      ability to use the method in conjunction with previous methods of bone blood flow
      measurement. The method is limited to the extent that only the contribution of
      the nutrient artery can be measured and total bone blood flow cannot be assessed.
      Tibial nutrient arterial flow and cardiac output were measured in adult mongrel
      dogs. Two experiments were performed: 1) bilateral baseline tibial nutrient
      artery blood flow measurements over time and 2) tibial nutrient blood flow
      comparing inhaled anesthesia (halothane/nitrous oxide/oxygen) and intravenous
      anesthesia (pentobarbital [Nembutal]). In 15 mongrel dogs, tibial nutrient artery
      blood flow averaged 1.46 +/- 0.72 mL/min (0.09 +/- 0.05 percent of cardiac output
      and 2.75 +/- 1.95 mL/min/100 g of bone). No significant difference in tibial
      nutrient artery blood flow was observed between animals given intravenous and
      inhaled anesthesia (P > .05). As a basic research tool, transit-time ultrasonic
      blood flow technology may be useful. The method is relatively easy to use and may
      be applied to experimental models designed to investigate various physiologic and
      pathologic states frequently encountered in orthopedics (eg, shock, sepsis,
      fractures).

PMID- 9243673
TI  - The use of the Ilizarov technique in the correction of lower extremity
      deformities in children.
AB  - The first time the Ilizarov technique was used at Children's Hospital of Los
      Angeles, 25 limb segments were treated in 15 patients. Thirteen segments (52%)
      required angular correction, 6 (24%) required lengthening, and 6 (24%) required
      both angular correction and lengthening. Average angular correction was 21
      degrees (8 degrees to 41 degrees); average length gained was 44 mm (25 to 85 mm).
      All patients except two achieved preoperative goals. A total of 17 minor
      (.68/limb) and four major (.16/limb) complications occurred in the 25 limb
      segments in the study. The total complication rate was .84 complications per limb
      segment. The most common complication was pin tract infection (11 patients). This
      comprised 52% of complications and occurred in 44% of limb segments.

PMID- 9243674
TI  - Pediatric septic arthritis.

PMID- 9243675
TI  - Imaging of tendon injuries about the ankle.

PMID- 9243676
TI  - Anterior unicortical buttress plating in conjunction with an unreamed
      interlocking intramedullary nail for treatment of very proximal tibial diaphyseal
      fractures.

PMID- 9243677
TI  - Acute gonococcal flexor tenosynovitis.

PMID- 9243678
TI  - A large ganglion cyst in a patient with hip dysplasia.

PMID- 9243679
TI  - Cauda equina syndrome due to sequestrated recurrent disk herniation after
      chiropractic manipulation.

PMID- 9243680
TI  - Intra-articular osteoid osteoma of the acetabulum in a 6 year old.

PMID- 9243681
TI  - The Internet and paediatric anaesthesia.

PMID- 9243682
TI  - Pain assessment in children.

PMID- 9243683
TI  - Intranasal ketamine preinduction of paediatric outpatients.
AB  - A double-blinded, placebo-controlled study compared the outcomes of intranasal
      ketamine premedication with placebo in outpatients. Forty paediatric outpatients
      were assigned randomly in a prospective fashion to one of two separate study
      groups of equal size (20 patients per group). A placebo group received 2 ml of
      intranasal saline, 1 ml per naris. The study group received intranasal ketamine,
      3 mg.kg-1, diluted to 2 ml with saline, 1 ml per naris. Using a cooperation
      index, a play therapist scored resistance to nasal instillation, separation of
      the child from parents at ten min, and acceptance of anaesthesia monitors and
      face mask at 15 min. Differences in age, weight, episodes of vomiting, recovery
      and discharge times among the two groups were not significant. Intranasal
      ketamine, 3 mg.kg-1, was associated with a significantly better (P = 0.013)
      cooperation index than intranasal placebo. Intranasal ketamine, permitted
      pleasant and rapid separation of children from their parents, cooperative
      acceptance of monitoring and of mask inhalation induction, and did not cause
      prolonged postanaesthetic recovery or delayed discharge home.

PMID- 9243684
TI  - Does thiopentone delay recovery in children premedicated with midazolam?
AB  - This prospective, randomized trial of paediatric surgical outpatients,
      premedicated with oral midazolam, was designed to determine if an intravenous
      thiopentone induction of anaesthesia prolongs postoperative recovery compared to
      an inhalation induction with halothane. One hundred children, one to ten years of
      age, undergoing ENT surgical procedures of 30-60 min duration received midazolam
      0.5 mg.kg-1 with atropine 0.03 mg.kg-1 and were randomized to either halothane
      (Group 1, n = 50) or a thiopentone induction (Group 2, n = 50) technique,
      followed by a standardized anaesthetic-protocol. Time to extubation was
      significantly greater in the thiopentone group (8.8 +/- 4 min vs 7.1 +/- 3 min, P
      < 0.05). Patients receiving thiopentone were also more sedated than the halothane
      group on arrival in the PARR (3.9 +/- 1.5, 3.3 +/- 1.7, respectively P < 0.05),
      but the differences disappeared after 30 min. Children premedicated with oral
      midazolam who receive an intravenous thiopentone induction have a slightly
      prolonged emergence from anesthesia compared to children induced with halothane.

PMID- 9243685
TI  - Oral midazolam compared with diazepam-droperidol and trimeprazine as premedicants
      in children.
AB  - Ninety children were assigned randomly to one of three groups for premedication
      with oral midazolam 0.5 mg.kg-1, diazepam 0.25 mg.kg-1 with droperidol 0.25 mg.kg
      1, or trimeprazine 2 mg.kg-1. On arrival at the anaesthetic room, anxiolysis was
      satisfactory in 26 out of 29 (90%) children who received midazolam compared with
      23 out of 29 (79%) who received diazepam-droperidol and 18 out of 29 (62%) who
      received trimeprazine (P < 0.05); at induction of anaesthesia these proportions
      were 24 out of 29 (83%), 16 out of 29 (55%) and 11 out of 29 (40%) respectively
      (P < 0.001). When individual groups were compared, anxiolysis was significantly
      greater in the midazolam group compared with the trimeprazine group on arrival in
      the anaesthetic room (P < 0.05) and significantly greater in the midazolam group
      than in either the diazepam-droperidol or the trimeprazine groups at induction of
      anaesthesia (P < 0.05 and P < 0.001 respectively). There were no significant
      differences in times to early recovery between the groups (25.4, 24.4 and 28.5
      min). Analysis of behavioural questionnaires completed two weeks after
      hospitalization showed a trend towards fewer postoperative behavioural
      disturbances in children who received midazolam or diazepam-droperidol compared
      with trimeprazine (47 and 44% vs 75%); when the results for the benzodiazepine
      containing premedicants were combined, the difference between these groups and
      trimeprazine was statistically significant (P < 0.05).

PMID- 9243687
TI  - Perioperative management of children with third degree heart block undergoing
      pacemaker placement: a ten year review.
AB  - It has been suggested that children with third degree heart block require
      insertion of a temporary pacemaker prior to general anaesthesia. This
      recommendation needs to be reevaluated with the availability of noninvasive
      transcutaneous cardiac pacing. We undertook a retrospective ten-year chart review
      of anaesthesia in children with third degree heart block undergoing pacemaker
      insertion or revision. Forty-eight children with complete heart block underwent
      seventy anaesthetics of which fifty three were in children without pacemakers or
      with nonfunctioning pacemakers. One child had a temporary pacemaker placed
      preoperatively following asystole in the emergency room. In children who were not
      being paced, 60% had baseline heart rates less than 60 bpm. Complications seen in
      this study, including hypotension, would not have been prevented by temporary
      pacemaker placement. We conclude that there is no benefit to routine preoperative
      temporary pacing in children with third degree heart block.

PMID- 9243686
TI  - The benefit of using a heat and moisture exchanger during short operations in
      young children.
AB  - We studied the efficiency of a heat and moisture exchanging filter (HMEF; Pall
      BB25) as a means of compensating for the heat and moisture loss during
      anaesthesia in young children using cold and dry gas supplied from open circuits.
      Forty ASA I children (mean age: 48 months +/- 20; mean weight: 16 +/- 3.5 kg)
      were randomized into two groups: Group I without HMEF/Group II with HMEF. The two
      groups did not show any significant differences for morphometric data or
      ventilation parameters. Relative humidity and temperature measurements in
      anaesthetic gases were taken using a combined temperature/humidity probe
      introduced into the circuit. Absolute humidity in the circuit was calculated from
      these measurements. In Group II, a significant increase (P < 0.001) in absolute
      humidity was demonstrated (Group I: 12 mg H2O.1(-1) vs Group II: 22 mg H2O.1(-1).
      This increase appeared immediately after introduction of the HMEF in the circuit
      and remained constant throughout the duration of the operation. Thus, the use of
      the device is recommended for young children, even for operations of short
      duration.

PMID- 9243688
TI  - Intermittent positive ventilation through a laryngeal mask in children: does it
      cause gastric dilatation?
AB  - After obtaining Ethics Committee approval and informed consent, sixty children,
      ASA Grade 1 or 2 and aged six months to ten years, were randomly allocated to
      receive intermittent positive pressure ventilation through either a laryngeal
      mask or a tracheal tube. Inflation pressures were maintained below 20 cm H2O, and
      gas aspirated from the stomach via an orogastric tube over a one h period. No
      large volumes were aspirated and no differences were detected between the groups.
      We conclude that healthy children over the age of six months can be safely
      ventilated through the laryngeal mask airway without gastric distension.

PMID- 9243689
TI  - A survey of pentobarbital sedation for children undergoing abdominal CT scans
      after oral contrast medium.
AB  - Radiologists have traditionally been responsible for the sedation of children
      undergoing radiological investigations. Anaesthetists are becoming increasingly
      involved in providing sedation and/or anaesthesia in this environment. The
      sedation of a child for a CT scan who has recently been given oral contrast
      medium (OCM) may pose anaesthetists a number of dilemmas. This is a retrospective
      survey of 149 intravenous pentobarbital sedations administered by radiologists to
      children (age range three months to seven years three months, weight range 5 kg
      to 28.9 kg) undergoing upper abdominal CT after recent ingestion of OCM. The
      average patient received pentobarbital 4.6 mg.kg-1. 141 patients (94.6%) received
      pentobarbital as the only sedative agent, whereas eight patients (5.4%) required
      supplementary sedation (midazolam +/- fentanyl). There were no failed sedations.
      36 complications occurred during 22 sedations (14.7% of total), with the most
      common being desaturation, vomiting, airway secretions, airway obstruction,
      coughing and bronchospasm.

PMID- 9243690
TI  - An audit of paediatric day care surgery in a district general hospital.
AB  - At a 620 bed District General Hospital, questionnaires were issued to the
      patients of 142 consecutive paediatric day surgery cases and the nurses involved
      in the care of these children. Most of the children were not upset by day case
      surgery, although nearly a quarter were distressed by changing into a theatre
      gown. Postoperatively, pain was more of a problem than nausea and vomiting.
      Relatively minor problems occurred at home. The majority of the 93 parents who
      replied were happy with the overall care of their child. They valued being
      present for induction of anaesthesia and would have liked to be present in
      recovery when their child was awake, although the nurses felt this would not have
      been helpful. Nonclinical matters also influenced their assessment of the quality
      of care.

PMID- 9243691
TI  - Conservative management of tracheal rupture after intubation.
AB  - A case is reported of a newborn with tracheal rupture resulting from a
      complicated delivery requiring vacuum extraction and two attempts at intubation.
      Despite the severity of the situation the infant was successfully managed
      conservatively with orotracheal intubation.

PMID- 9243692
TI  - Primary congenital pulmonary hypoplasia--genetic component to aetiology.
AB  - Primary congenital pulmonary hypoplasia, defined as congenital pulmonary
      hypoplasia occurring in the absence of other congenital anomalies, is an
      exceedingly rare condition of unknown aetiology. We report on two cases that
      presented as severe progressive respiratory failure immediately after birth in
      siblings of a consanguinous marriage, and we postulate that a genetic aetiology
      may be responsible for the arrest of lung maturation in utero. The possibility of
      a genetic component to the aetiology has not been previously documented in the
      literature.

PMID- 9243694
TI  - Anaesthetic management during awake craniotomy in a 12-year-old boy.
AB  - We present our approach to the preoperative preparation and anaesthetic
      management for awake craniotomy in a 12-year-old boy. Management included
      conscious sedation with a propofol infusion plus local anaesthetic infiltration
      of the scalp, periosteum, and dura. The complications which may be encountered
      during such procedures and their treatments are reviewed.

PMID- 9243693
TI  - Successful weaning from cardiopulmonary bypass after cardiac surgery using
      inhaled nitric oxide.
AB  - Two cases of very difficult weaning from cardiopulmonary bypass after cardiac
      surgery in children with pulmonary hypertension and ventricular dysfunction are
      reported. Children fail to respond to conventional therapy combining
      nitrovasodilators and inotropic support and react successfully to combined
      inhaled nitric oxide (NO) and epinephrine or left atrial infused norepinephrine.
      Postoperative NO inhalation must be prolonged and no toxicity appears. Pulmonary
      endothelial function recovers only after several days.

PMID- 9243695
TI  - Freeman-Sheldon (whistling face) syndrome. Anaesthetic and airway management.
AB  - We describe the anaesthetic management of Freeman-Sheldon syndrome in a two-and-a
      half year old undergoing club foot correction. Following an inhalational
      induction using halothane, tracheal intubation by direct laryngoscopy proved
      impossible. A laryngeal mask airway was inserted and intubation with a 4.5
      tracheal tube was successfully achieved using a fibreoptic bronchoscope passed
      through the LMA. The child had an uneventful anaesthetic course. A caudal
      epidural was used for postoperative analgesia and the child was discharged home
      on day two. The anaesthetic and airway management options of this syndrome are
      outlined.

PMID- 9243697
TI  - Anaesthesia in children with viral respiratory tract infections (Paediatric
      Anaesthesia 5: 257-262)

PMID- 9243698
TI  - Difficult diagnosis of a primitive pharyngeal dyskinesia with a size 1 laryngeal
      mask airway in an ex-premature baby.

PMID- 9243696
TI  - Oral and nasotracheal light wand guided intubation after failed fibreoptic
      bronchoscopy.
AB  - Fibreoptic bronchoscopic guided tracheal intubation is often the first choice for
      clinicians familiar with the technique, when faced with a patient in whom
      tracheal intubation presents known or possible difficulties. Regardless of the
      technique chosen, anticipated and unanticipated problems may arise. We report
      three patients with known difficult airways that illustrate the utility of light
      wand guided oral and nasotracheal intubation when tracheal intubation with
      fibreoptic bronchoscopy proved impossible.

PMID- 9243700
TI  - Population review: (9). Summary of issues.
AB  - Previous population reviews--published as the 1977 and 1984 Demographic Reviews-
      were published as free-standing reports. This Review has appeared, initially, as
      a series of eight articles in this journal. The aim (to quote from the
      introduction in Population Trends 81) has been to: 'describe the changing make-up
      of the population of the United Kingdom in a form that will be useful to both
      general readers and to demography specialists'. The articles have shown that
      since the 1984 review was issued the demographic picture has become clearer-and
      now looks a little different. This concluding article brings together the key
      changes since the last Review and summarises the current situation.

PMID- 9243701
TI  - Population review: (8). The ethnic minority and overseas-born populations of
      Great Britain.
AB  - This article gives a brief history of immigration into Britain this century as an
      introduction to a description of the size and main characteristics of the
      different ethnic minority populations living in Britain today. Using data from
      the 1991 Census-the first to include a question on ethnic group-the article
      covers the demographic background and main features of Britain's present-day
      ethnic minority populations and provides an introduction to the wealth of
      analyses which has followed the release of ethnicity data from the 1991 Census.

PMID- 9243699
TI  - Durability of tunnelled central venous catheters in children with malignant
      diseases.

PMID- 9243702
TI  - The time taken to register a death.
AB  - This article analyses delays in the registration of death and discusses their
      effect on mortality statistics. It is shown that the longest delays arise when
      deaths are the subject of a coroner's inquest, in particular deaths in road
      traffic accidents. These delays mean that it may be many months before an
      acceptable proportion of deaths occurring in a year have been registered, so
      affecting how early a reliable extract of annual data can be taken. It also shows
      that the difference in the number of deaths occurring and the number registered
      in a year is strongly influenced by the weekdays on which holidays fall at the
      New Year.

PMID- 9243703
TI  - Stimulation of the production of progesterone by the corpus luteum of the ewe by
      the perfusion of melatonin in vivo and by treatment of granulosa cells with
      melatonin in vitro.
AB  - The ability of melatonin to stimulate luteal steroidogenesis directly in the ewe
      was investigated by using a perfusion cannula system in vivo and luteinised
      granulosa cells in vitro. Exposure to human chorionic gonodotrophin (hCG) or
      ovine luteinising hormone (oLH), as positive controls, significantly stimulated
      progesterone secretion by the perfused corpus luteum within 20 minutes and by
      granulosa cells after two days of culture. Melatonin perfused through the corpus
      luteum at a physiological concentration, significantly stimulated progesterone
      secretion but the response was not as rapid as that to hCG. The significant
      stimulation of progesterone by melatonin in the perfusion system was maintained
      for between 30 and 60 minutes. Melatonin significantly stimulated progesterone
      production by granulosa cells in vitro after two days of culture, but the degree
      of response depended on the size of the follicles from which the cells were
      obtained. These results demonstrate that melatonin can act directly on the corpus
      luteum to increase progesterone production, and that its mechanism of action
      appears to be different from that of hCG or oLH in the ewe. This action of
      melatonin may be related to the reported improved luteal function late in the
      breeding season after the prolonged exposure of ewes to melatonin.

PMID- 9243704
TI  - Oxidative energy metabolism in equine tendon cells.
AB  - Hypoxia has been suggested as a possible cause of tissue degeneration and
      subsequent rupture in equine tendons. To determine whether low oxygen tension is
      likely to be detrimental to tendon cell function, experiments were designed to
      investigate oxidative energy metabolism in freshly isolated and cultured equine
      tendon cells. Freshly isolated tenocytes and cultured fibroblasts possessed
      activities of the mitochondrial enzyme citrate synthase similar to those of other
      mammalian cells, with well defined oxidative metabolism. D-[6(-14)C]-glucose
      oxidation was measurable in both freshly isolated and explant-derived cells. The
      content of adenosine triphosphate (ATP) in cultured cells was decreased by
      incubation with a mitochondrial respiratory uncoupler. These data demonstrate
      that tendon cells are capable of oxidative energy metabolism and rely upon it to
      maintain cellular ATP levels. Hypoxia must therefore be considered as a possible
      factor leading to tendon degeneration and subsequent injury.

PMID- 9243706
TI  - Effects of oxytocin, arginine-vasopressin and lysine-vasopressin on insulin and
      glucagon secretion in sheep.
AB  - The effects of the posterior-pituitary peptides oxytocin (OT), arginine
      vasopressin (AVP) and lysine-vasopressin (LVP) on insulin and glucagon secretion
      were examined in adult sheep. Each peptide was injected intravenously at doses
      from 1 to 3000 pmol kg-1. All three peptides increased plasma insulin and
      glucagon concentrations, but their dose-response relationships revealed
      differences between them. The maximal insulin responses induced by OT and AVP
      were very similar, but the threshold and maximal doses of AVP for increasing
      plasma insulin were higher than those of OT. OT and AVP had the same activity for
      stimulating glucagon secretion in respect of the threshold and maximal doses and
      the maximal hormone response. LVP also increased plasma insulin and glucagon
      concentrations, but it had the weakest activity for stimulating both hormones.
      These results suggest that in sheep posterior-pituitary peptide may play a role
      in regulating nutrient metabolism by influencing pancreatic hormone secretion.

PMID- 9243705
TI  - Anti-alpha chain monoclonal antibodies of equine MHC class-II antigens:
      applications to equine infectious anaemia.
AB  - This paper describes the characteristics of a monoclonal antibody (mAb), 6B11C3,
      that recognises most equine monocytic cells, as well as B- and T-lymphocytes. The
      T CD4+ and T CD8+ of this latter population are also stained by the 6B11C3 mAb.
      On the basis of the distribution of membrane antigens on these cell populations,
      and of immunohistochemistry results, this mAb appears to be an anti-equine class
      II major histocompatibility complex (MHC) antigen. In horses, the hyperexpression
      of the MHC class-II antigen on T cells is an indication of activated lymphocytes.
      A decrease in the percentage of lymphocytes stained by 6B11C3 was observed in
      horses with persistent equine infectious anaemia.

PMID- 9243708
TI  - Comparative pharmacokinetics of netobimin metabolites in pregnant ewes.
AB  - The pharmacokinetics of netobimin (NTB) metabolites has been investigated in
      ewes. Non-pregnant ewes and ewes in the first and last third of pregnancy were
      dosed orally with 20 mg kg bodyweight of NTB. Blood samples were collected from
      the jugular vein from 30 minutes to 72 hours after administration and plasma
      samples were analysed by high performance liquid chromatography. Neither NTB nor
      albendazole (ABZ) were detected in any of the samples analysed. No statistically
      significant differences were found between the pharmacokinetic parameters of
      albendazole suphoxide (ABZSO) and albendazole sulphone (ABZSO2) among the three
      groups of ewes. The peak plasma concentrations (Cmax) ABZSO and ABZSO2 were
      reached about 10 and 20 hours respectively after administration in all three
      groups. The ratios of ABZSO/ABZSO2 for Cmax and the areas under the curve
      (AUCzero-infinity) were 6 and 3, respectively, in each group and suggest a low
      rate of oxidation of sulfoxide to sulphone.

PMID- 9243707
TI  - Effect of the mycotoxins penitrem, paxilline and lolitrem B on the
      electromyographic activity of skeletal and gastrointestinal smooth muscle of
      sheep.
AB  - The electromyographic (EMG) activity of skeletal muscle was investigated as a
      method of recording the tremorgenic activity of the mycotoxins penitrem,
      paxilline and lolitrem B in sheep. EMG recordings were made concurrently from the
      abomasal antrum and duodenum to study the effects of these tremorgens on smooth
      muscle of the gut. Penitrem (2.2 to 7.5 micrograms kg-1) induced mild to moderate
      tremors within 15 to 20 minutes of injection which lasted for two to four hours.
      Paxilline (0.66 to 1.5 mg kg-1) induced mild to moderate tremors immediately
      which lasted for one to two hours. Lolitrem B (25 to 110 micrograms kg-1) had no
      effect at low doses, but at higher doses it produced tremors appearing over 20 to
      30 minutes which persisted for more than 24 hours. The best measure of tremor
      indicated by skeletal muscle EMG was recorded from the shoulder area. The
      responses of smooth muscle of the antrum and duodenum to the tremorgens were
      variable. They included inhibitory effects on the antrum but no stimulation. The
      tremorgens had inhibitory effects on the duodenum on some occasions but on
      others, phase III migrating myoelectric complex-like activity was stimulated.

PMID- 9243709
TI  - Morphological and biochemical investigations of mitral valve endocardiosis in
      pigs.
AB  - Pig endocardiosis is a pathological process affecting cardiac valves that is
      characterised by the accumulation of glycosaminoglycans (GAG) in the
      extracellular matrix. To investigate the involvement of GAG in the condition, the
      morphology of the mitral valves from 23 affected pigs and seven normal controls
      was studied and qualitative and quantitative biochemical analyses of GAG were
      made. Gross and histopathological lesions were characterised by valve
      enlargement, collagen disorganisation and myxoid degeneration. No differences
      between normal and diseased valves were detected by lectin histochemistry.
      Electron microscopy revealed myofibroblast differentiation of many fibroblasts. A
      statistically significant increase of total GAG and hyaluronan was detected in
      the mitral valves of the pigs with endocardiosis by spectrophotometric,
      electrophoretic and densitometric analysis of the extracted GAG. Although it is
      not known whether the change in hyaluronan is a primary event or a result of
      other changes in the extracellular matrix, its accumulation in association with
      myofibroblast differentiation suggests that it plays a pathogenetic role in pig
      endocardiosis.

PMID- 9243710
TI  - Characterisation of embryonic cardiac-derived troponin T in broiler chicks bled
      one to 168 hours after hatching.
AB  - Troponin T, a cardiac-specific protein released only from damaged or injured
      heart tissue and cells, was measured in the sera from fowl chicks bled one, 12,
      24, 48, 96 and 168 hours after hatching. A peak troponin T response was observed
      12 hours after hatching in two experiments conducted six months apart. In the
      second experiment the heterophil/lymphocyte (H/L) ratios were also increased at
      one and 12 hours after hatching. The data suggest that the troponin T response in
      chicks bled 12 hours after hatching, together with the raised H/L ratios at the
      same age, may indicate a physiological stress reaction to the process of
      hatching, rather than a process which is under direct genetic control.

PMID- 9243711
TI  - Effects of neutering on bodyweight, metabolic rate and glucose tolerance of
      domestic cats.
AB  - Few controlled studies have been made of the possible mechanisms and
      physiological consequences of weight gain after cats have been neutered. In this
      study, six male and six female cats were gonadectomised and compared with five
      entire male and six entire female cats, before they were neutered and one and
      three months later. The neutered males gained significantly more weight (mean
      [SEM] per cent) than the entire males (30.2 [5.2] v 11.8 [2.3]) and the entire
      females gained 40.0 (7.3) v 16.1 (3.3) per cent, (P < 0.05). The castrated males
      gained more weight as fat than the sexually intact males (22.0 [3.3] v 8.8 [4.5]
      per cent, P < 0.05). There was a significant increase (P < 0.05) in daily food
      intake after neutering. Spayed females underwent a significant decrease in
      fasting metabolic rate (83.7 [5.5] v 67.2 [2.3] kcal/kg bodyweight0.75/day P <
      0.05). Gonadectomy had minimal effects on serum thyroid hormone concentrations,
      the resting or fasting metabolic rates in males, or on indices of glucose
      tolerance.

PMID- 9243712
TI  - Detection of serum haptoglobin by enzyme-linked immunosorbent assay in cows with
      fatty liver.
AB  - Haptoglobin cannot be detected in the serum of healthy cattle by the haemoglobin
      binding assay or single radial immunodiffusion. The present study was designed to
      examine whether an enzyme-linked immunosorbent assay could be applied to measure
      serum haptoglobin concentrations in healthy cows and in cows with fatty liver.
      When either purified cow haptoglobin or haptoglobin-positive serum were used as
      the antigen in the assay, the standard curves obtained were distinctly different,
      and haptoglobin in serum was detected more sensitively than the purified protein.
      The addition of bovine serum albumin to purified haptoglobin shifted the curve
      towards that obtained with haptoglobin-positive serum, suggesting that an
      interaction with serum albumin was partly responsible for the different standard
      curves. By use of the standard curve for haptoglobin in serum, the mean (SEM)
      concentration of haptoglobin in samples from four cows with fatty liver was 466
      (147) micrograms ml-1, but the sera from four apparently healthy cows contained
      less than 0.01 microgram ml-1 haptoglobin.

PMID- 9243713
TI  - The effect of doxapram-induced hyperventilation on respiratory mechanics in
      horses.
AB  - To investigate the influence of increased respiratory frequency on respiratory
      mechanics in the horse, measurements were made in two groups of seven
      tracheostomized horses before and after the administration of doxapram. The
      horses in group I had normal base line values for respiratory mechanics, whereas
      the horses in group II had significantly lower values of dynamic compliance
      (Cdyn), higher respiratory resistance (R), and a higher total change in pleural
      pressure (delta P). The administration of 0.3 mg kg-1 doxapram intravenously
      resulted in a significant increase in respiratory frequency (fR), R, delta P,
      tidal volume (VT), and peak to peak respiratory flow (V), and a decrease in Cdyn
      in both groups of horses. The group II horses had significantly greater increases
      in R and delta P than the horses in group I.

PMID- 9243714
TI  - Methods for the isolation, culture and characterisation of equine pulmonary
      artery endothelial cells.
AB  - Equine endothelial cells were isolated from the pulmonary artery by enzymatic
      digestion and grown to confluency. The cells were characterised by positive
      immunofluorescent staining for von Willebrand factor and NADPH-diaphorase
      staining for nitric oxide synthase. Measurements of endothelins indicated that
      there were significant release rates from the cells for up to six hours.
      Measurements of intracellular calcium concentration showed that the application
      of bradykinin caused a transient increase in calcium concentration with similar
      characteristics to those observed in other endothelial cell preparations. These
      tests verify the endothelial character of these cells and establish the method as
      a reliable means of producing a primary culture of equine endothelial cells.

PMID- 9243715
TI  - Responses of glucose absorption and fructose absorption to prostaglandin E2 in
      intestinal loops of sheep.
AB  - This study was designed to clarify whether the anti-absorptive action of
      prostaglandin E2 (PGE2) on glucose absorption was specific or non-specific to the
      glucose absorptive process, by investigating its effect on fructose absorption
      which has a different mechanism from that of glucose absorption. The effect of
      PGE2 on mucus secretion was also evaluated as one of the non-specific inhibiting
      factors. PGE2 significantly stimulated the secretion of water and mucus, and the
      absorptions of glucose and fructose were inhibited 49.3 per cent and 31.1 per
      cent respectively at the highest dose. However, fructose absorption was not
      inhibited by lower doses of PGE2, although the secretion of fluid and mucus was
      stimulated significantly and glucose absorption was inhibited significantly at
      the lower doses.

PMID- 9243716
TI  - Effects of alfentanil on the equine electroencephalogram during anaesthesia with
      halothane in oxygen.
AB  - Opioids have variable effects on the minimum alveolar concentration of inhaled
      anaesthetics in the horse. During halothane anaesthesia at an end-tidal halothane
      concentration between 0.75 and 0.85 percent, the electroencephalogram (EEG)
      frequency power spectrum and the auditory evoked potential were recorded
      continuously in eight ponies during an infusion of approximately 40 micrograms kg
      1 alfentanil over five minutes, and for a further 55 minutes. The spectral edge
      and median frequency of the EEG and the mid-latency of the auditory evoked
      potential at the time of maximum change of these variables were compared with
      those recorded before the start of the infusion. The mean (SD) spectral edge and
      median frequencies were reduced by 26 (5) percent and 36 (6) percent
      respectively. The mid-latency of the auditory evoked potential did not change.
      These cortical effects of alfentanil in the horse are qualitatively the same as
      in other species, suggesting that the alfentanil-induced excitement observed in
      horses in not of cortical origin.

PMID- 9243717
TI  - Keratin pattern in hyperkeratotic and ulcerated gastric pars oesophagea in pigs.
AB  - Ulceration of the gastric pars oesophagea is a serious problem in the pig
      industry, and in spite of numerous studies the underlying mechanisms of the
      development of such ulcers remains largely unknown. The present study was
      designed first to test the hypothesis that the epithelium of the pars oesophagea
      of affected pigs would be more susceptible to the irritating action of acidic
      gastric content owing to a change in the pattern of expression of keratin, and
      second to look for a member of the keratin family that could be a suitable
      indicator of early lesions. Samples were collected from the gastric pars
      oesophagea of slaughter pigs with and without grossly visible mucosal changes,
      and the keratin patterns of normal and hyperkeratotic and ulcerated epithelium
      were compared immunohistochemically. The keratin pairs K 4/K 13, and K 5/K 14
      were present in both normal and affected epithelia, and had a similar pattern of
      expression in both conditions. K 4 and K 13 were expressed in all the suprabasal
      layers, and K 5 and K 14 were expressed only in the basal and epibasal cells.
      Immunological reactivity with the monoclonal antibodies LL020 and LHK6-markers
      for hyperproliferative conditions-was present in the suprabasal layers of the
      epithelium of the hyperkeratotic and the ulcerated pars oesophagea but not in the
      normal epithelium. These results indicate that K 6 is expressed in association
      with the mucosal changes. The pattern of the intermediate filaments of keratin
      suggests that in basic to gastric ulcers in pigs there is an epithelial
      proliferation leading to visible hyperkeratosis.

PMID- 9243718
TI  - Effects of C-terminal fragments of cholecystokinin on plasma insulin and glucagon
      concentrations in sheep.
AB  - The effects of three C-terminal fragments of cholecystokinin (CCK) (CCK-8
      sulphated form [SF], CCK-8-non-sulphated form [NSF] and CCK-4) on insulin and
      glucagon secretion were examined in sheep in vivo. Each CCK fragment was injected
      intravenously at a wide range of doses (1 pmol to 3 x 10(5) pmol kg-1). CCK-8(SF)
      had the lowest threshold dose (10 pmol kg-1) and a maximal response dose of 10(3)
      pmol kg-1 for increasing plasma insulin concentration; the respective threshold
      doses of CCK-8(NSF) and CCK-8 for increasing plasma insulin were 30 and 100 times
      greater than that of CCK-8(SF). A maximal insulin response was not obtained at
      the highest doses of CCK-8(NSF) or CCK-4 tested (3 x 10(3) and 3 x 10(5) pmol kg
      1, respectively). These results indicate that CCK-A type receptors rather than
      CCK-B receptors may be involved in CCK-induced insulin secretion in sheep. None
      of the CCK fragments affected plasma glucagon concentration. The lack of a
      glucagon response to exogenous CCK-fragments may be one of the characteristics of
      the endocrine pancreatic responses of ruminant species.

PMID- 9243719
TI  - Anticoccidial efficacy of toltrazuril and halofuginone against Eimeria tenella
      infection in broiler chickens in Egypt.
AB  - The anticoccidial activities of toltrazuril and halofuginone against Eimeria
      tenella were tested in broiler chickens. Comparisons were made between
      ummedicated infected and uninfected control birds in addition to infected groups
      given either toltrazuril at 37.5, 75 and 150 ppm in the drinking water, or
      halofuginone at 1.5, 3 and 6 ppm in the feed. Both drugs were highly efficacious
      against E tenella. Treatment improved the bodyweight gain and survival percentage
      in comparison with the unmedicated, infected group. Intestinal lesions, faecal
      and oocyst scores and oocyst shedding in dropping were significantly reduced by
      both drugs. Toltrazuril gave better protection than halofuginone; 75 and 150 ppm
      toltrazuril in drinking water gave good protection when administered four and
      five days after inoculation.

PMID- 9243720
TI  - A pharmacodynamic study of propofol or propofol and ketamine infusions in ponies
      undergoing surgery.
AB  - The pharmacodynamics of infusions of propofol alone (group 1) were compared with
      the pharmacodynamics of infusions of propofol and ketamine together (group 2) in
      eight ponies undergoing castration. Anaesthesia was induced with detomidine, 20
      micrograms kg-1, followed by ketamine, 2.2 mg kg-1. Subsequently, a bolus dose of
      propofol, 0.5 mg kg-1, was administered intravenously to both groups, and an
      infusion of propofol was given for an average of 74 minutes to group 1, and an
      infusion of propofol and ketamine was given for 60 minutes to group 2. The mean
      (SD) infusion rates of propofol were 0.330 (0.050) mg kg-1 min-1 in group 1, and
      0.124 (0.009) mg kg-1 in group 2, and the ketamine infusion rate was maintained
      constant at 40 micrograms kg-1 min-1. Arterial hypotension and marked respiratory
      depression were evident in some of the ponies receiving propofol alone, whereas
      in the ponies anaesthetised with propofol and ketamine, respiratory and
      cardiovascular parameters were well maintained. All the ponies in both groups
      recovered quickly from anaesthesia, with mean times to sternal recumbency and
      standing of 19.8 (8.0) minutes and 27.2 (7.4) minutes respectively for group 1
      and 8.4 (3.2) min and 14.9 (10.1) minutes for group 2.

PMID- 9243721
TI  - Plasma erythropoietin concentrations in dogs and cats: reference values and
      changes with anaemia and/or chronic renal failure.
AB  - Reference ranges of plasma erythropoietin concentration measured by immunoassay
      in 67 healthy cats and 40 healthy dogs were 1.9 to 22.9 mU ml-1 and 1.3 to 13.4
      mU ml-1 respectively. Very significant increases of plasma erythropoietin
      concentration were observed in 22 cats and 32 dogs with anaemia without chronic
      renal failure (CRF), but 35 cats and 37 dogs with CRF had normal or moderately
      reduced erythropoietin concentrations. In cats there was almost no overlap of
      erythropoietin between the groups but in dogs there was a significant overlap.
      The measurement of plasma erythropoietin is therefore probably more useful in the
      diagnosis of anaemia in cats than in dogs, either with or without CRF.

PMID- 9243722
TI  - The effect of the long-term administration of vasopressin on the development of
      the kidneys of growing lambs.
AB  - The effects of long-term administration of l-desamino-D-arginine vasopressin
      (dDAVP) on the macromorphology of the kidneys were studied in young growing
      lambs. Subcutaneous injections of dDAVP were started two weeks after birth and
      lasted for 13 weeks. Morphometric measurements showed that the volume of the
      cortex was reduced and both the height and volume of medulla were significantly
      increased in the dDAVP-treated lambs. The increase in the size of the medulla was
      mainly due to changes to the dimensions of the outer medulla. The surface area of
      the renal pelvis was enlarged by 29 per cent in the dDAVP-treated group. The mean
      (SEM) surface area of the renal pelvis of 15-week-old lambs was 5957 (365) mm2.
      These changes induced by an increased supply of vasopressin could have a
      beneficial effect on the recycling of urea and the concentrating ability of the
      kidneys.

PMID- 9243723
TI  - Gluten-sensitive enteropathy in Irish setter dogs: characterisation of jejunal
      microvillar membrane proteins by two-dimensional electrophoresis.
AB  - This study investigated whether gluten-sensitive enteropathy (GSE) in Irish
      setter dogs was associated with underlying structural abnormalities of
      microvillar membrane proteins. Jejunal biopsies taken from eight-month-old GSE
      affected dogs reared on a normal, gluten-containing diet exhibited partial
      villous atrophy and contained more intra-epithelial lymphocytes than controls.
      The morphological abnormalities were reversed by feeding a gluten-free diet for
      five months and the changes were accompanied by an increase in the mucosal
      activity of the microvillar hydrolases, particularly aminopeptidase N and
      dipeptidyl aminopeptidase IV, which reverted to pre-treatment levels after a
      gluten challenge. Two-dimensional electrophoresis of microvillar membrane
      proteins isolated from GSE-affected dogs revealed an essentially normal protein
      map that was comparable to controls. The exception was an intense 85 kDa protein
      spot that diminished when the affected dogs were fed a gluten-free diet and re
      intensified after a gluten challenge.

PMID- 9243724
TI  - Teratogenicity of Aino virus in the chick embryo.
AB  - Aino virus (JaNAr 28 strain), a possible agent of a congenital anomaly of calves,
      was inoculated into the yolk sac of chick embryos at a dose of 10(2), 10(3),
      10(4) or 10(5) TCID50 0.2 ml-1 at four, six or eight days of incubation. At 21
      days of incubation all the unhatched embryos or hatched chickens in the
      experimental and control groups were sacrificed for pathological examination. The
      incidence of hydranencephaly, cerebellar hypoplasia or agenesis and
      arthrogryposis or scoliosis was highest (85 per cent in the chicks inoculated
      with 10(3) TCID50 0.2 ml-1 at eight days of incubation. The lesions were very
      similar to those found in congenital abnormalities in calves suspected of a
      natural infection with Aino virus.

PMID- 9243725
TI  - Evidence-based intervention for musculoskeletal disorders.

PMID- 9243726
TI  - Vocational outcome of intervention for low-back pain.
AB  - Practical management guidelines for occupational health physicians are needed for
      the individual support of employees with low-back pain. In this study the level
      of evidence regarding the efficacy of intervention with vocational outcome
      parameters was assessed. In a systematic literature search, 40 randomized
      clinical trials on different types of intervention were retrieved. Their internal
      validity and statistical power criteria were assessed. The randomization
      procedure, blinding of patients, and sample size were problematic in most
      studies. For patients with acute low-back pain limited or moderate evidence was
      found for the efficacy of no bed rest, a short period of bed rest, and spinal
      manipulation. For chronic patients limited evidence was found for the efficacy of
      antidepressants. For the other types of intervention, studies with sufficient
      statistical power were lacking. Such studies are needed before more-detailed
      evidence-based guidelines can be formulated for occupational health care.

PMID- 9243727
TI  - Psychosocial job factors associated with back and neck pain in public transit
      operators.
AB  - OBJECTIVES: This cross-sectional study examined associations between psychosocial
      job factors and the prevalence of nondisabling back and neck pain in professional
      drivers after physical work load was taken into account. METHODS: A total of 1449
      transit vehicle operators completed a medical examination and a questionnaire
      yielding information on demographic and anthropometric variables, health status,
      and physical and psychosocial job factors. Company records were used to
      supplement information on employment history. Physical work load was measured in
      life-time years and current weekly hours of professional driving. The relation of
      psychosocial factors with back or neck pain was analyzed by logistic regression
      models adjusted for past and current physical work load, vehicle type, age,
      gender, body height, and weight. RESULTS: The main result of this study was that
      both physical work load and psychosocial factors were simultaneously and
      independently associated with back or neck pain. Psychosocial factors associated
      with back or neck pain included extended uninterrupted driving driving periods,
      frequency of job problems, high psychosocial demands, high job dissatisfaction,
      and low supervisory support. An analysis of specific job problems is provided
      which may be useful in setting priorities for research and intervention efforts
      in this high risk occupation. CONCLUSION: The results provide support for the
      role of psychosocial job characteristics in the etiology of back or neck pain in
      occupational settings.

PMID- 9243728
TI  - Lung cancer incidence among an Icelandic cohort exposed to diatomaceous earth and
      cristobalite.
AB  - OBJECTIVES: The objective of this study was to determine the cancer incidence of
      a cohort exposed to diatomaceous earth and cristobalite with special focus on
      lung cancer. METHODS: The cohort was from a diatomaceous plant in northern
      Iceland and comprised 919 men and 423 women. Diatomite, when heated, is
      transformed from amorphous to crystalline silica with a high cristobalite content
      and traces of quartz. With the use of the identification number of all persons, a
      link was made with the Cancer Registry. The expected number of malignancies was
      calculated on the basis of person-years of observation for 5-year age categories
      during the respective calendar period of the study multiplied by the specific
      incidence of cancer site for men and women in Iceland. RESULTS: There was no
      increased overall incidence of cancer in the study population; 5 cases of lung
      cancer were observed versus 4.4 expected, the standardized incidence ratio (SIR)
      was 1.14 [95% confidence interval (95% CI) 0.37-2.65]. When the men in the cohort
      were divided according to their length of employment, there was an excess of lung
      cancer (3 observed versus 1.28 expected, SIR 2.34, 95% CI 0.48-6.85), nonmelanoma
      skin cancer (2 observed versus 0.19 expected, SIR 10.53, 95% CI 1.27-38.02), and
      brain cancer (3 observed versus 0.30 expected, SIR 10.00, 95% CI 2.06-29.23) for
      those who had worked 5 years or longer. A special investigation of smoking habits
      among the cohort revealed a smoking pattern similar to that of the general
      population. CONCLUSION: The results concerning lung cancer showed an excess risk
      for workers exposed to diatomaceous earth and cristobalite; the result was not,
      however, statistically significant. There was a trend towards a higher incidence
      of lung cancer with longer exposure to crystalline silica, and, in agreement with
      the results of a previous study from this industry, the findings indicate a
      causal relation.

PMID- 9243729
TI  - Short-term effect of hand-arm vibration exposure on tactile sensitivity and
      manual skill.
AB  - OBJECTIVES: The present study investigated whether the impairment of tactile
      sensitivity after exposure to vibration disturbs the motor control of precision
      handling and, if so, whether it can result in an increased risk of injury during
      or after tasks involving the use of vibrating tools. METHODS: Twelve men were
      manually exposed to vibration from an electric sander for 30 min. Cutaneous
      sensitivity was quantified to measuring the pressure perception threshold and
      vibration perception threshold (125 Hz) on the pulp of the second finger.
      Manipulative skill was evaluated by grip-lift movements and the Purdue pegboard
      test. RESULTS: The vibration perception threshold increased very significantly
      from 94.0 dB (0.06 m/s2) before the vibration exposure to 127.5 dB (3.2 m/s2)
      immediately after the exposure. The pressure perception threshold tended to
      increase after vibration exposure, although not significantly, but manipulative
      skill was not altered. CONCLUSIONS: Change in vibration perception threshold was
      not associated with a significant increase in the pressure perception threshold
      or a perturbation of manual skill. Therefore, in conditions similar to those of
      our experiment, the safety of a precision task does not appear to be reduced
      after such vibration exposure.

PMID- 9243730
TI  - Urinary 1-naphthol excretion in the assessment of exposure to creosote in an
      impregnation facility.
AB  - OBJECTIVES: This study explored the possibility of using urinary 1-naphthol
      excretion as a marker of complex exposure among workers handling creosote.
      METHODS: Urine specimens of 6 workers from a creosote impregnation plant, where
      railroad ties were impreganted with coal tar creosote, were collected during 1
      workweek, and the concentration of 1-naphthol was determined. 1-Naphthol in spot
      urine samples of 5 occupationally nonexposed male smokers was used as the
      background reference. Concurrently, naphthalene and 10 different polycyclic
      aromatic hydrocarbons (PAH) were determined in personal air samples. RESULTS: The
      mean airborne exposure of the workers was 1.5 mg/m3 for vaporous naphthalene, 5.9
      micrograms/m3 for particulate PAH and 1.4 micrograms/m3 for PAH with 4-6 aromatic
      rings. The mean urinary concentration of 1-naphthol at the end of the workshift
      was 20.5 (range 3.5-62.1) mumol/l, whereas the referents' urinary concentration
      was below the detection limit (0.07 mumol/l). Airborne naphthalene correlated
      fairly well with 1-naphthol when measured at the end of the shift (r = 0.745).
      CONCLUSIONS: This method of analysis for 1-naphthol is sufficiently sensitive for
      measuring low occupational exposures to naphthalene. Low background exposures
      are, however, unlikely to result in detectable urinary levels of 1-naphthol.
      Since naphthalene is the most abundant compound in creosote vapor, urinary 1
      naphthol determination serves well as a biological marker of exposure to vaporous
      creosote. Urinary 1-naphthol alone is not, however, a suitable marker for
      inhalatory or cutaneous exposure to PAH originating from creosote.

PMID- 9243731
TI  - Are deficits in the equilibrium system relevant to the clinical investigation of
      solvent-induced neurotoxicity?
AB  - OBJECTIVES: The diagnosis of solvent-induced chronic toxic encephalopathy is
      commonly based on case histories of exposure to solvents, symptoms, and deficits
      on psychometric tests. It has previously been demonstrated that long-term solvent
      exposed workers have disturbances of the equilibrium system. The correlation
      between these disturbances and the diagnosis of chronic toxic encephalopathy has
      been analyzed in the present study. MATERIAL AND METHODS: Sixty men,
      consecutively admitted due to the suspicion of this syndrome, were investigated
      and classified into 3 groups--solvent-induced chronic toxic encephalopathy,
      incipient chronic toxic encephalopathy and nonchronic toxic encephalopathy. They
      were all examined using an otoneurological test battery, including analysis of
      saccades, smooth pursuit, visual suppression of the vestibular ocular reflex, and
      dynamic posturography. RESULTS: Compared with healthy referents several of the
      subjects, even in the nonchronic toxic encephalopathy group, showed a reduced
      visual suppression ability, a prolonged latency of saccades, and pathological
      posturographic results. Some otoneurological tests correlated with the duration
      of exposure and the results of psychometric tests representing memory and
      perceptual skills. Nevertheless, there was no significant group correlation
      between the otoneurological findings and the diagnosis of chronic toxic
      encephalopathy. CONCLUSION: Disturbances revealed by an otoneurological
      investigation have so far not been considered in the diagnosis of chronic toxic
      encephalopathy. Our results indicate that an otoneurological test battery adds
      worthwhile information about lesions within the brainstem-cerebellar complex not
      revealed by a psychometric investigation.

PMID- 9243733
TI  - Coronary heart disease mortality among Newfoundland fluorspar miners.
AB  - OBJECTIVES: The association between cumulative radon exposure and coronary heart
      disease mortality was studied in a retrospective cohort investigation of
      Newfoundland fluorspar miners. METHODS: Multivariate Poisson regression
      techniques were used to estimate relative risks of coronary heart disease
      mortality by level of radon exposure. Relative risks (RR) were adjusted by
      attained age, calendar period, duration of exposure, and smoking status. Death
      from coronary heart disease was the outcome measure of interest and was
      identified by record linkage to the Canadian Mortality Database. RESULTS: An
      elevated risk of mortality from coronary heart disease was observed among miners
      with a cumulative radon exposure exceeding 1000 working-level months [RR 1.5, 95%
      confidence interval (95% CI) 0.77-2.75]. The association between radon exposure
      and coronary heart disease was not statistically significant according to a test
      for trend across exposure categories (P = 0.09). The smokers were 1.8 times more
      likely than the nonsmokers to die from coronary heart disease (95% CI 1.1-2.8).
      CONCLUSIONS: These results suggest a positive association between coronary heart
      disease and radon exposure. However, these findings should be interpreted
      cautiously due to the inability to control for the confounding influence of other
      known risk factors of coronary heart disease.

PMID- 9243732
TI  - Specific antibodies against methyltetrahydrophthalic anhydride and risk factors
      for sensitization in occupationally exposed subjects.
AB  - OBJECTIVES: Occupational exposure to methyltetrahydrophthalic anhydride (MTHPA)
      from an epoxy resin was studied to evaluate the nature of reported ocular and
      nasal complaints and some risk factors for sensitization. METHODS: Seventy-three
      current and 22 former workers underwent a questionnaire survey and serologic
      investigations. Total and MTHPA-specific immunoglobulin (Ig)E levels were
      measured by means of a Pharmacia CAP system, and MTHPA-specific immunoglobulin
      (Ig)E levels were measured by enzyme immunoassay. RESULTS: Forty-six (63%) of the
      currently exposed workers has positive MTHPA-specific IgE, and no significant
      difference was found between those continuously or intermittently exposed (58%
      and 71%, respectively). Work-related ocular or nasal symptoms were significantly
      associated with specific IgE but not with specific IgG4. This finding indicates
      that there is an IgE-mediated mechanism in most cases of work-related symptoms
      associated with MTHPA exposure. The total IgE levels were significantly (P <
      0.005) higher in the specific IgE-positive workers than in the specific IgE
      negative workers (geometric mean 101 IU/ml and 44.8 IU/ml, respectively).
      Multiple logistic regression analysis also revealed that the group with high
      total IgE levels (> or = 80 IU/ml) had a significant relative risk (RR 4.7) of
      producing MTHPA-specific IgE as compared with the group with low total IgE levels
      (< 80 IU/ml). CONCLUSIONS: These results show that MTHPA has a high sensitizing
      ability and that a high total IgE level is the most significant risk factor for
      workers exposed to MTHPA. However, to evaluate conclusively the effect of high
      total IgE levels on sensitization, further prospective studies are necessary.

PMID- 9243734
TI  - Airway isocyanate-adducts in asthma induced by exposure to hexamethylene
      diisocyanate.
AB  - OBJECTIVES: The clinical features, airway histology, and detection of
      hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a
      patient with HDI asthma are described. METHODS: Isocyanate asthma was diagnosed
      by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was
      performed 24 h after challenge and immunohistochemical staining was performed.
      RESULTS: Airway biopsies obtained at bronchoscopy demonstrated inflammatory
      changes typical for asthma, including increased airway eosinophils and T cells.
      Immunohistochemical staining with specific anti-HDI antibodies demonstrated the
      presence and localization of HDI adducts in human bronchial biopsies.
      CONCLUSIONS: These studies confirm epithelial exposure to HDI following workplace
      challenge and demonstrate the feasibility of detecting and localizing isocyanate
      adducts in human lung tissue. Identifying and characterizing the airway
      macromolecules to which isocyanates bind in vivo are probably crucial to the
      understanding of how isocyanates cause sensitization and asthma. The ability to
      detect isocyanate adducts may also help characterize isocyanate exposure patterns
      and exposure-disease relationships.

PMID- 9243735
TI  - Statistical significance--a misconstrued notion in medical research.
AB  - The P-value is the significance probability of obtaining a value of the test
      statistic that is as extreme, in relation to the null hypothesis, as that
      observed. Medical researchers may, in some situations, disagree on its
      appropriate use or on its interpretation as a summary measure of consistency with
      the null hypothesis in a particular data set. More informative statistical
      measures such as the likelihood ratio and the Bayesian posterior probability have
      been suggested for drawing inferences from clinical trials and epidemiologic
      studies. Causal inference is not statistical in nature; rather it strives to
      provide scientific explanations or criticisms of proposed explanations that would
      describe the observed data pattern. In this context, it is important to remember
      that a finding may not be medically important, or a causal hypothesis may even
      not be true even if a study shows a significant P-value.

PMID- 9243736
TI  - Sex under the influence. A diary self-report study of substance use and sexual
      behavior among adolescent women.
AB  - OBJECTIVE: To evaluate the potential causal relationship between alcohol and drug
      use and behavior that increases the risk of sexually transmitted diseases. STUDY
      DESIGN: Longitudinal study conducted at a sexually transmitted diseases clinic
      and four community-based primary care clinics for adolescents. The participants
      were 82 female adolescents (age 16-19 years) who agreed to complete diaries
      recording each coital event. Subjects were participants in a larger study of
      prevention of reinfections by sexually transmitted organisms. The main outcome
      measure was condom use at each coital event. Predictor variables were usual
      pattern of condom use (when substances were not involved) and two event-specific
      measures: sex partner change and use of alcohol or drugs before intercourse.
      RESULTS: Average time span of the diaries was 9.2 weeks. Subjects recorded 1,265
      coital events. Ninety-three substance-associated coital events were recorded by
      22 subjects. Event-specific condom use was associated with usual pattern of
      condom use, but not with event-specific variables of partner change or substance
      use before intercourse. CONCLUSIONS: These data do not support the hypothesis
      that substance use causes alteration of adolescent women's behavior in a manner
      that increases risk of sexually transmitted diseases.

PMID- 9243737
TI  - Intoxications, intentions, and disease preventions.

PMID- 9243738
TI  - Sex, drugs, and infections among youth. Parenterally and sexually transmitted
      diseases in a high-risk neighborhood.
AB  - BACKGROUND AND OBJECTIVES: To determine the extent to which youth who reside in
      households in a neighborhood with large numbers of drug injectors 1) are infected
      with parenterally or sexually transmitted agents, and 2) engage in high-risk
      behaviors. STUDY DESIGN: A multistage probability household sample survey was
      conducted in Bushwick, Brooklyn from 1994 to 1995. All households in 12 randomly
      selected primary sampling units were screened for age-eligible youth. One hundred
      eleven English-speaking 18- to 21-year-olds were interviewed. One hundred three
      sera were tested for human immunodeficiency virus type 1 (HIV-1), Hepatitis B
      virus, hepatitis C virus (HCV), human T-cell lymphotrophic virus types I and II
      (HTLV-I/II), herpes simplex virus type 2 (HSV-2), or syphilis. Urines were tested
      for chlamydial infection, and for opiate and cocaine metabolites. RESULTS: Eighty
      nine percent had sex in the past year, 45% with two or more partners. Only 19% of
      the sexually active always used condoms. Two (of 95) had had sex with a crack
      smoker. Thirty percent of women reported being coerced the first time they had
      sex, and 23% of women and 3% of men reported having been sexually abused. Only 3%
      reported ever using heroin, and 9% cocaine. Only one reported ever having
      injected drugs or smoked crack. Some underreporting of stigmatized behaviors
      occurred: two "nonreporters" had opiate-positive urines and two had cocaine
      positive urines. Marijuana use was common, with 48% using it in the past year. No
      subjects tested positive for HIV-1, HIV-II, or syphilis; 2% tested positive for
      HTLV-I and 3% for hepatitis C; 3% had hepatitis B markers, 12% had chlamydial
      infection, and 50% serologic HSV-2 markers. CONCLUSIONS: Population
      representative samples of high-risk communities can provide important knowledge.
      Although heroin and cocaine use, during drug injection, and rates of infection
      with parenterally transmitted infectious agents appear to be lower among these
      youth, sexual risk behaviors and chlamydial and HSV-2 infection are widespread.
      Sexually transmitted disease screening and outreach strategies are needed both to
      prevent sexually transmitted disease sequelae (including potential increased
      susceptibility to HIV infection) and to prevent transmission to partners.

PMID- 9243739
TI  - Sexual networks of African-American and Hispanic youth.
AB  - BACKGROUND AND OBJECTIVES: To describe the characteristics of several types of
      sexual partners of African-American and Hispanic urban youth and to determine the
      association of these characteristics with condom use, contraceptive use,
      experience with sexually transmitted diseases, and sexual practices. STUDY
      DESIGN: Data were drawn from personal interviews with a probability sample of low
      income urban youth, age 15 to 24 years, conducted in Detroit in 1991 (N = 1,435).
      RESULTS: Although both ethnic groups tended to form partnerships most often
      within their own group. Hispanics had sexual partners who varied by ethnicity
      much more than did African Americans. Furthermore, the longer-term relationships,
      those that resulted in marriage or cohabitation, were more likely to be with
      Hispanic partners than were other relationships. Hispanic men were also more
      likely to report white partners than were Hispanic women. In contrast, for
      African-American men and women, most reported relationships were with other
      African Americans. Regardless of ethnicity or relationship type, women had older
      partners than did men. Partner differences in age or ethnicity showed few or no
      differences in condom use, reports of sexually transmitted disease, oral
      intercourse, or use of contraceptive methods. CONCLUSIONS: Although relationships
      with people of similar age and ethnicity are common, bridges exist for
      transmission of sexually transmitted infection between different age and ethnic
      groups.

PMID- 9243740
TI  - Partner referral by patients with gonorrhea and chlamydial infection. Case
      finding observations.
AB  - OBJECTIVE: To evaluate the outcomes of a partner referral program at the sexually
      transmitted disease (STD) clinic in Amsterdam that encourages gonorrhea and
      chlamydia patients to refer their own partners to medical examination. STUDY
      DESIGN: 355 patients with a confirmed infection cooperated in partner referral
      and gave specific details on their sexual contacts. Univariate and multivariate
      analyses were conducted to identify characteristics associated with the outcome
      of partner referral. RESULTS: The outcome of partner referral, expressed as the
      proportion of sex partners brought to evaluation or treatment, was 40%: 580 sex
      partners were identified of whom 20% attended the STD clinic, and medical follow
      up could be confirmed for another 20%. No information was available for the
      remaining 60%. Patients with chlamydial infection referred more sexual partners
      than gonorrhea patients; women referred more partners than men. Sixty-three
      percent of the female contacts and 30% of the male contacts were found to be
      infected with gonorrhea, chlamydia, or both. Steady partners were more often
      referred by index patients than casual partners, especially if these latter were
      non-Dutch partners, clients of commercial sex workers, contacts met in less
      private settings, and "one night stands." CONCLUSIONS: Partner referral can be an
      effective strategy for reaching individuals at high risk for STD. The partner
      referral method was successful among certain populations but was inadequate for
      other groups. A mixed effort of provider referral in addition to partner referral
      may be appropriate to increase the efficacy of partner notification.

PMID- 9243741
TI  - First-void urine testing for Chlamydia trachomatis by polymerase chain reaction
      in asymptomatic women.
AB  - BACKGROUND: Because Chlamydia trachomatis infections are usually asymptomatic or
      minimally symptomatic, diagnosis is often delayed. GOAL: To perform a comparative
      study of first-void urine (FVU) polymerase chain reaction (PCR) testing and
      endocervical swab antigen testing in the diagnosis of C. trachomatis infection
      among asymptomatic women. STUDY DESIGN: The study population consisted of 1,090
      unselected women attending a family planning clinic or a university student
      health clinic. Calculations of test performances were based on an expanded
      reference standard including enzyme immunoassay (EIA) or PCR tests confirmed by
      direct fluorescence antibody (DFA) test or major outer membrane protein PCR test,
      respectively. RESULTS: The overall prevalence of C. trachomatis infection was
      5.6%. After resolution of discrepant specimens, FVU PCR detected 85% (52/61) and
      endocervical swab EIA/DFA 90% (55/61) of confirmed positive cases. CONCLUSIONS:
      These results indicate that the FVU PCR test is an accurate, noninvasive
      screening method and can replace endocervical swab EIA in the detection of C.
      trachomatis infection in low-prevalence populations.

PMID- 9243742
TI  - Predictors of human immunodeficiency virus counseling and testing among sexually
      transmitted disease clinic patients.
AB  - OBJECTIVES: To determine the predictors of prior or current, and repeat human
      immunodeficiency virus (HIV) testing. STUDY DESIGN: Cross-sectional survey.
      METHODS: Sexually transmitted disease (STD) clinic patients who participated in a
      blinded HIV seroprevalence survey completed a voluntary questionnaire regarding
      their reasons for accepting or declining HIV testing. RESULTS: Eighty-seven
      percent of participants reported a previous HIV test or were HIV testing the day
      they completed the questionnaire. African Americans were less likely to have been
      HIV tested (adjusted odds ratio 0.3, 95% confidence limits, 0.1, 0.8). The most
      common reasons for testing were to be reassured and to receive medical care if
      infected. The most common reason for not testing was that nontesters did not
      think that they were infected. Repeated testing was reported by 51% of the
      participants and was more frequent among patients who were older or members of
      high-risk groups (P < 0.05). Patients tested repeatedly to confirm a prior HIV
      test result or because of continued risky behavior. CONCLUSIONS: Testing for HIV
      is frequent among STD clinic patients but less so among African Americans.
      Receipt of medical care appears to be an important motivation for HIV testing,
      whereas lack of perceived risk may discourage testing. Continued high-risk
      behavior contributes to repeat HIV testing.

PMID- 9243744
TI  - Trichomoniasis in pregnancy.

PMID- 9243743
TI  - Trichomonas vaginalis associated with low birth weight and preterm delivery. The
      Vaginal Infections and Prematurity Study Group.
AB  - BACKGROUND: Several studies have suggested that pregnant women infected with
      Trichomonas vaginalis may be at increased risk of an adverse outcome. GOAL: To
      evaluate prospectively the association between T. vaginalis and risk of adverse
      pregnancy outcome in a large cohort of ethnically diverse women. STUDY DESIGN: At
      University-affiliated hospitals and antepartum clinics in five United States
      cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were
      enrolled at mid-gestation, tested for T. vaginalis by culture, and followed up
      until delivery. RESULTS: The prevalence of T. vaginalis infection at enrollment
      was 12.6%. Race-specific prevalence rates were 22.8% for black, 6.6% for
      Hispanic, and 6.1% for white women. After multivariate analysis, vaginal
      infection with T. vaginalis at mid-gestation was significantly associated with
      low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm
      delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm
      delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval
      1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low
      birth weight weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in
      whites. CONCLUSIONS: After considering other recognized risk factors including co
      infections, pregnant women infected with T. vaginalis at mid-gestation were
      statistically significantly more likely to have a low birth weight infant, to
      deliver preterm, and to have a preterm low birth weight infant. Compared with
      whites and Hispanics, T. vaginalis infection accounts for a disproportionately
      larger share of the low birth weight rate in blacks.

PMID- 9243745
TI  - Clinical sexually transmitted diseases among human immunodeficiency virus
      infected and noninfected drug-using prostitutes. Associated factors and
      interpretation of trends, 1986 to 1994.
AB  - OBJECTIVES: To describe among drug-using prostitutes from the Amsterdam cohort
      study: 1) trends in clinical sexually transmitted disease (STD) diagnoses from
      1986 through 1994; 2) identify factors associated with STD incidences; and 3)
      determine explanatory factors for time trends in STD. METHODS: Sexual behavior
      data and human immunodeficiency virus (HIV) serostatus from the cohort study were
      linked to diagnoses of gonorrhea (GC), Chlamydia trachomatis infection (CT), and
      trichomoniasis (TV) made at a special STD clinic for drug-using prostitutes.
      Diagnosis-specific incidences were calculated per 100 person-years of follow-up.
      Factors associated with STD incidence were determined bivariately. Crude time
      trends in incidences were determined and then multivariately adjusted for sets of
      potential explanatory factors using Poisson regression. RESULTS: Cohort data from
      229 current prostitutes were linked to clinical STD diagnoses. During the study
      period, a fivefold decline in GC was found, and CT declined twofold; trends in TV
      initially declined, but tended to increase after 1991. Higher incidences for STD
      were associated with inconsistent condom use, higher numbers of clients, shorter
      history of prostitution, younger age, non-Dutch nationality, and HIV infection.
      About half of the decline in STD could be explained by changes toward safer
      commercial sexual behaviours or changes in the characteristics of the study
      population. CONCLUSIONS: From 1986 through 1994, the incidence in clinical STD
      declined significantly among drug-using prostitutes in Amsterdam. Trends in STD
      were only partly due to risk reduction in commercial sexual contacts. Thus, it
      may be hazardous to use trends in STD as markers for sexual risk behavior. Other
      factors probably played a substantial role in the observed declines, including
      declining STD prevalence among male clients, changes in health-seeking behaviors,
      and improved quality of STD control.

PMID- 9243746
TI  - Self-treatment patterns among clients attending sexually transmitted disease
      clinics and the effects of self-treatment on STD symptom duration. The Study
      Group.
AB  - OBJECTIVE: To assess patterns of self-treatment and its effects on the duration
      of sexually transmitted disease (STD) symptoms before medical care. METHODS: A
      cross-sectional interview survey in public STD clinics (7 U.S. cities). Patients,
      seeking treatment for STD symptoms or having a known infected sexual contact,
      reported self-treatment behaviors and symptom duration. Additional data were
      abstracted from medical charts. RESULTS: Self-treatment, primarily over-the
      counter topical medications (54.8%), was reported by 21.8% of 2,508 symptomatic
      patients. Self-treaters were significantly more likely to be African-American
      (odds ratio [OR] = 1.8), female (OR = 1.7), over age 30 (OR = 1.3), report > 1
      symptom (OR = 1.4), and report a genital lesion (OR = 2.1). Symptom duration was
      2 days longer among self-treaters (p < 0.01). African-Americans (OR = 1.5), men
      (OR = 1.2), and self-treaters of symptoms other than genital lesions (OR = 1.4)
      had a significantly longer time from symptom onset to receiving medical care.
      CONCLUSIONS: Self-treatment is common among patients with STDs. Self-treatment of
      a genital lesion, unlike certain demographic factors and self-treatment of other
      STD symptoms, did not prolong the time to medical treatment.

PMID- 9243747
TI  - Antimicrobial susceptibility and types of Neisseria gonorrhoeae in Greece. Data
      for the period 1990 to 1993.
AB  - BACKGROUND: Surveillance of the rapidly changing patterns of antimicrobial
      resistance of Neisseria gonorrhoeae is imperative for monitoring gonococcal
      infection. GOAL: To describe the types and the antimicrobial susceptibility
      profile of a representative samples of gonococci isolated in Greece between 1990
      and 1993. STUDY DESIGN: The antimicrobial susceptibilities, serovar/auxotypes
      classes, and plasmid contents of 263 consecutive isolates of N. gonorrhoeae,
      recovered from cases of male gonococcal urethritis, were determined. RESULTS:
      Penicillinase-producing N. gonorrhoeae (PPNG) were isolated at a rate of 6.1% and
      were mostly from imported cases of infection. Six (2.3%) of the isolates (one
      PPNG and five non-PPNG) were highly resistant to tetracycline, and one PPNG
      strain was resistant to norfloxacin and ciprofloxacin. Strains with chromosomal
      resistance to penicillin, tetracycline, erythromycin, and chloramphenicol
      accounted for 18.5%, 12.5%, 19%, and 16% of the isolates, respectively; much
      higher proportions of strains were intermediately susceptible to these
      antibiotics. Spectinomycin and cefotaxime were active against all gonococci
      studied. A shift to IB serovars and to sporadic types of strains was noted from
      previous years among the non-PPNG isolates. This is compatible with the marked
      increase in the rate of imported cases of infection caused by n on-PPNG strains.
      CONCLUSIONS: The emergence of high-level resistance to tetracycline and
      resistance to fluoroquinolones was ascertained. At the present, however, the main
      problem with gonococcal resistance in Greece seems to ensue from the increasing
      rates of chromosomally resistant strains. Moreover, the increasing frequency of
      imported gonococci underlines the necessity for continuous epidemiologic
      surveillance.

PMID- 9243748
TI  - Induction of nuclear factor kappa B/Rel nuclear activity in human peripheral
      blood T lymphocytes by anti-HLA class I monoclonal antibodies.
AB  - Monoclonal antibodies against either monomorphic or polymorphic determinants of
      class I antigen induced in PBMC and highly purified T lymphocytes the nuclear
      activity of NF-kappa B/Rel complexes. These included both p50/p50 and p50/p65
      dimers, recognized by specific antibodies in EMSA. The induced complexes were
      detectable in extracts of cells incubated with anti-class I monoclonal antibody
      (mAb) for 1.5 h; the induction was maximal at 5 h, persistent at 16 h and no
      longer observed at 40 h. The mAb failed to induce NF-kappa B/Rel nuclear activity
      in cells incubated in the presence of 3,4-dichloroisocoumarin, an inhibitor of I
      kappa B-alpha degradation. Together, these results suggest that class I
      triggering can induce the activity of NF-kappa B/Rel nuclear activity in
      peripheral blood T lymphocytes, thereby modulating the expression of genes
      regulated by these transcription factors.

PMID- 9243749
TI  - Contribution of human leukocyte antigens to the antibody response to hepatitis B
      vaccination.
AB  - We present here the analysis of 86 individuals who were true antibody
      nonresponders to a vaccine containing hepatitis B surface antigen. The HLA type
      of these individuals and of 248 controls were determined by serology for HLA
      class I and by molecular typing for the HLA class II loci DRB1 and DQB1.
      Subsequent analysis of the results revealed that HLA-DRB1*0701 and HLA-DQB1*02
      were significantly associated with antibody non-response to the "S"-containing
      vaccine compared with the HLA control population. Further, we found that the
      antibody non-response was also significantly associated with the above antigens
      when found in linkage disequilibrium on the HLA haplotype DRB1*0701; DQB1*0202.
      The hepatitis B surface antigen vaccine antibody nonresponder group, comprising
      86 individuals, were revaccinated with a novel vaccine Hep B-3, containing both
      preS1- and preS2-derived proteins in addition to hepatitis B surface antigen, to
      circumvent their previous nonresponsiveness. The hepatitis B surface antigen
      antibody results from this group of patients show that 30 of the 86 individuals
      remained antibody non-responders and that 24 individuals (80%) expressed the HLA
      DQB1*02 and that 21 individuals (70%) expressed HLA-DRB1*0701. Our results
      indicate that antibody nonresponse to the Hep B-3 vaccine is significantly
      associated with an extended HLA haplotype B44; DRB1*0701; DQB1*0202. A possible
      indication of these results is that antibody nonresponse to Hep B-3 vaccine is
      linked with the HLA allele DQB1*0202. These findings may have an important impact
      on future vaccine design.

PMID- 9243750
TI  - The HLA-DQ(alpha 1*0102, beta 1*0602) heterodimer may confer susceptibility to
      multiple sclerosis in the absence of the HLA-DR(alpha 1*01, beta 1*1501)
      heterodimer.
AB  - The frequencies of DR2, DQ6-related DRB1, DQA1, DQB1 haplotypes were compared in
      181 multiple sclerosis patients and 294 controls in Norway. All individuals
      carried either DR2 or DQ6, i.e., the DQ(alpha 1*0102, beta 1*0602) heterodimer.
      The DR(alpha 1*01, beta 1*1501) and the DQ(alpha 1*0102, beta 1*0602)
      heterodimers were carried by 171 of the patients (94%) and 289 (98%) of the
      controls. Seven of the patients and one of the controls carried the DQ(alpha
      1*0102, beta 1*0603) heterodimer together with the DR(alpha 1*01, beta 1*1501)
      heterodimer. Two patients carried the DQ(alpha 1*0102, beta 1*0602) heterodimer
      in the absence of the DR( alpha 1*01, beta 1*1501) heterodimer. The DR(alpha
      1*01, beta 1*1501) heterodimer was not observed in the absence of the DQ(alpha
      1*0102, beta 1*0602) heterodimer or the DQ(alpha 1*0102, beta 1*0603)
      heterodimer, neither in the patients nor in the controls. Our findings indicate
      that the genes encoding the DQ(alpha 1*0102, beta 1*0602) heterodimer may confer
      susceptibility to developing multiple sclerosis in the absence of the DRB1*1501
      allele.

PMID- 9243751
TI  - Polymerase chain reaction haplotyping using 3' mismatches in the forward and
      reverse primers: application to the biallelic polymorphisms of tumor necrosis
      factor and lymphotoxin alpha.
AB  - A polymerase chain reaction with sequence-specific primers (PCR-SSP) system that
      operates under identical conditions to HLA phototyping was devised for
      characterizing polymorphisms in tumor necrosis factor (TNF) and lymphotoxin alpha
      (LT-alpha). Mismatches at the 3' end were incorporated into the forward and
      reverse primers of each PCR so as to unequivocally establish the cis/trans status
      between the biallelic sites. Three previously described biallelic polymorphisms
      in TNF and three in LT-alpha were characterized in a 24-reaction PCR-SSP system.
      The method was used to genotype 20 cell lines and 201 HLA class I and II typed
      controls from the United Kingdom at the TNF and LT-alpha loci. Population
      frequencies of TNF haplotypes were determined as was linkage disequilibrium with
      HLA-A, B, Cw, DRB1 and DQB1 loci. In each gene there were 8 theoretical
      polymorphic combinations; 4 were observed in TNF and 4 in LT-alpha. A total of 11
      TNF-LT-alpha haplotypes were determined from apparent homozygous controls and
      statistical analysis.

PMID- 9243752
TI  - A new HLA-B44 variant (B44BO [B*4408]) identified by serology.
AB  - Using HLA serology, we detected a new variant of HLA-B44- B44BO- in two families.
      This antigen reacts with B44 antisera and is negative with over one-third of B12
      (B44, B45) sera but reacts with 50% antisera with a B62 component, especially if
      they contain anti-B57. The variant, B*4408, differs from the common B*4402 by 4
      nucleotide substitutions in exon 2: 193, 206 and 209, which produce changes in
      the the alpha 1 domain at positions 41, 45 and 46 (TKE in B*4402 and AMA in
      B44BO); and nucleotide 213, a silent substitution. At each of these positions,
      B*4408 is identical to B*46 B*57 and may B*15 alleles. As anticipated from its
      predicted iso-electric point (5.71), one-dimensional isoelectric focusing studies
      showed that B44BO focuses at the same position as B*4402. The sequence and
      serological reactivity of this rare antigen allowed the identification of two
      likely epitopes shared by two different groups of HLA-B antigens.

PMID- 9243753
TI  - Complete coding regions of two novel HLA-B alleles detected by phototyping (PCR
      SSP) in the British caucasoid population: B*5108 and B*5002.
AB  - Two previously reported PCR-SSP variants of the HLA-B locus, B51GAC and B45v,
      were investigated by RT-PCR cloning and nucleotide sequence analysis of their
      complete coding regions. They have been shown to correspond to the new alleles
      B*5108 and B*5002, both of which differ from the common B*5101 and B*5001
      subtypes, respectively, by amino acid replacements at their alpha-2 domain alpha
      helices. The primary structure of B*5002, intermediate between those of B*4501
      and B*5001, raises further concern about the current classification of B*45 as a
      B12 rather than as a B*50 subtype.

PMID- 9243754
TI  - Identification of four new DR52-associated DRB1 alleles: DRB1*1424, *1425, *1323
      and *1324.
AB  - Four previously unreported DR52-associated DRB1 alleles have been characterized
      through DNA sequencing, contributing to the diversity of the HLA system.
      DRB1*1424 is nearly identical to DRB1*1402 in the second exon, except that it
      contains the "I---A" motif found at codons 67-71 common to the DRB1*15 alleles.
      DRB1*1425 contains the "A--H" motif, found in DRB1*1401 at codons 57-60, in a
      sequence otherwise identical with the second exon of DRB1*1307. Compared with
      DRB1*11012, DRB1*1323 contains three predicted amino acid changes at codons 58
      (ala-->glu), 67 (phe-->ile), and 71 (arg-->glu). The sequence of DRB1*1324 is
      identical to exon 2 of DRB1*1103, except that DRB1*1324 does not contain the GAG
      at codon 58 characteristic of the DRB1*11 alleles. These new alleles may have
      arisen through gene conversion, and they contribute to the complexity of the DR6
      family.

PMID- 9243755
TI  - Association of the TNFa2 microsatellite allele with the presence of colorectal
      cancer.
AB  - Independently, our two groups collaborating in this report performed association
      studies to consider the influence of the TNF region within the human MHC on the
      presence of colorectal cancer. In the Glasgow Study, 84 colorectal cancer
      patients were compared with 91 controls at the TNFa microsatellite locus.
      Analysis of individual alleles by Fisher's exact test revealed a significant
      overrepresentation of the TNFa2 allele in the colorectal cancer group, after
      correcting for multiple comparisons. In the Essen Study, 47 colorectal cancer
      patients were compared with 117 matched controls, and the hypothesis of TNFa2
      overrepresentation in colorectal cancer was confirmed. These data provide
      evidence for the involvement of the TNF locus in the pathogenetic etiology of
      colorectal cancer.

PMID- 9243756
TI  - Absolute linkage of celiac disease and dermatitis herpetiformis to HLA-DQ.
AB  - This report shows the absolute genetic linkage of celiac disease (CD) to the HLA
      DQ region, and supports the fact that dermatitis herpetiformis (DH) follows the
      same pattern of HLA-mediated susceptibility in extensive series of Caucasian
      Spanish patients. Ninety-five percent of CD (201 of 212) and 100% of DH (55)
      patients could produce DQ alpha 1*0501-DQ beta 1*02 heterodimers. Negative CD
      patients for this combination were mostly DR4-DQ8 (DQA1*03-DQB1*0302) (9 OF 11),
      along with a restricted number of complementary chromosomes. Comparison of
      observed and expected DQA1-DQB1 genotype distributions (Hardy-Weinberg
      equilibrium) showed that the excess of patients with DQB1*02 in double doses
      would be the consequence for which this allele should be complemented by
      DQA1*0501. Homozygosity for DQA1*0501 would restrain susceptibility to CD and DH.

PMID- 9243757
TI  - A strong association between HLA-B*5101 and Behcet's disease in Greek patients.
AB  - Behcet's disease is known to be associated with HLA-B51, one of the split
      antigens of HLA-B5, among many different ethnic groups. In a Greek population, an
      increased incidence of HLA-B5 in the patient group has also been reported.
      Because the B51 antigen has been recently identified to comprise seven alleles,
      B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as
      well as serological HLA-A and -B typing among 31 Greek patients with Behcet's
      disease to investigate whether there is any correlation between one particular
      B51-associated allele and Behcet's disease. The frequency of B51 was remarkably
      high (80.6%) in the patient group as compared to the ethnically matched control
      group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as
      compared with the healthy controls (3.3%). B51 allele genotyping revealed that
      all these B51-positive patients carried B*5101. This study revealed a strong
      association of Behcet's disease in Greeks with one of the B51 subantigens,
      providing insight into the molecular mechanism underlying an HLA association with
      Behcet's disease.

PMID- 9243758
TI  - Analysis of critical residues of HLA-DQ6 molecules in insulin-dependent diabetes
      mellitus.
AB  - Among DQ6 molecules, DQA1*0102-DQB1*0602 is negatively associated with insulin
      dependent diabetes mellitus (IDDM), but DQA1*0102-DQB1*0604 shows a neutral to
      positive association in Swedish children with IDDM. The aim of this study was to
      identify critical DQB1 residues that may account for the differences in IDDM
      association observed for these two DQ6 molecules. HLA-DQ genotyping in 425 IDDM
      patients and 367 matched controls showed DQ6 (B1*0602) in 1% of patients and 25%
      of controls (odds ratio (OR) 0.02). DQ6 (B1*0604) alone was neutral (9% of
      patients and 10% of controls) but in combination with DQ8, was positively
      associated (5% of patients, 1% of controls, OR 9.49). In both these DQ6 molecules
      the alpha-chain is the same but the beta-chain differs at positions 9, 30, 57,
      70, 86 and 87. DQB1*0602 has F9, Y30, D57, G70, A86 and F87, whereas DQB1*0604
      has Y9, H30, V57, R70, G86 and Y87. Three-dimensional models of the two DQ6
      molecules, based on crystal coordinates of the homologous DR1 molecule, suggest
      that residue 57 beta will likely play a critical role in peptide-binding
      selectivity, whereas residue 70 beta is probably is major contact site for the T
      cell receptor. The effects of these specific polymorphic substitutions in DQ
      molecules on peptide binding and T-cell receptor recognition may be significant
      in IDDM susceptibility.

PMID- 9243760
TI  - Heat shock protein 70 gene polymorphisms in rheumatoid arthritis.
AB  - A role for heat shock proteins (hsp) in rheumatoid arthritis has been suggested.
      In addition, the specific binding of human HSP70 protein to QKRAA and RRRAA
      motifs within the HV3 region of disease-associated DRB1*0401 and DRB1*1001
      molecules, respectively, has been proposed as being relevant to rheumatoid
      arthritis. The purpose of this work was to analyze the influence of HSP70 gene
      polymorphism on the susceptibility to or severity of rheumatoid arthritis and to
      investigate the possible contribution of these HSP70 polymorphisms in determining
      HLA-DRB1*0401/*1001 disease association. The frequencies of the HSP70-1, HSP70-2
      and HSP70-hom genotypes were analyzed by PCR-RFLP using BsrBI, PstI and NcoI
      enzymes, respectively, in patients with rheumatoid arthritis and in healthy
      controls. No significant differences were observed when HSP70 allele distribution
      between the groups under study were compared. Moreover, we did not observe any
      significant difference in HSP70 allele frequencies between patients positive for
      HLA-DRB1*0401/*1001 alleles and matched controls. Our data indicate that HSP70
      gene polymorphisms do not appear to be relevant in the susceptibility to or
      severity of rheumatoid arthritis.

PMID- 9243759
TI  - Triplet repeat polymorphism in the NOTCH4 gene with the human major
      histocompatibility complex in a healthy population and patients with a salivary
      gland tumor in Japan.
AB  - The NOTCH4 gene, the human counterpart of the mouse mammary tumor gene, int-3,
      has been recently localized near the boundary of the HLA class II and class III
      regions. This gene is one of candidates for development of salivary gland tumor.
      Microsatellite polymorphism of (CTG)n repeat in the signal peptide domain of
      NOTCH4 was analyzed in Japanese including the patients with salivary gland tumor.
      Four alleles consisting of 6, 9, 10 and 11 repetitions of CTG (Leu) were observed
      and found to be in linkage disequilibria with HLA class I and class II alleles.
      No significant association of this microsatellite polymorphism with the disease
      were observed in 26 samples of salivary gland tumor. In this neoplasia, neither
      large-scale deletion nor translocation was detected around the NOTCH4 gene using
      genomic Southern hybridization analysis by the NOTCH4 cDNA as a probe.

PMID- 9243761
TI  - Dimorphic primers derived from intron 1 for use in the molecular typing of HLA-B
      alleles.
AB  - We have identified a dimorphic site in intron 1 of the HLA-B gene. Oligotyping
      was performed on about 3000 samples using primers derived from this dimorphic
      site in combination with a locus-specific primer derived from intron 3. The
      distribution of B-alleles bearing each of the dimorphic sequences was
      approximately equal. These primers were mutually exclusive and yielded
      approximately 50% of the heterozygous samples as apparently homozygous in PCR
      products. Intermediate and almost high-resolution oligotyping of HLA-B alleles
      was achieved using 35 and 63 hybridization probes, respectively. This dimorphic
      site will provide a useful tool for other PCR-based HLA-B typing approaches.

PMID- 9243762
TI  - Increased diversity within the HLA-A*66 group: implications for matching in
      unrelated bone marrow transplantation.
AB  - We have identified a new A*66 allele (A*6603) in three related individuals, an
      Arabic patient suffering from acute myeloid leukemia and two of her relatives.
      The A*66 alleles differ in three amino acid residues at positions 70, 90 and 163.
      The closer relationship between A*6602 and A*6603, which only differ at amino
      acid 70, replacing GLN with HIS, suggests that the alloreactive potential in this
      mismatch combination is lower than in all other mismatched A*66 donor-recipient
      combinations, which exhibit two (A*6601 versus A*6602) and three (A*6601 versus
      A*6603) differences at the pivotal positions, respectively. This emphasizes the
      potential role of the A*66 subtypes in bone marrow transplantation with
      alternative donors. For that reasons, allelic subtyping should be considered in
      donor-recipient matching to identify the kind of disparity.

PMID- 9243763
TI  - Full-length cDNA nucleotide sequence of the HLA-B*4202 allele.

PMID- 9243764
TI  - Lack of HLA-DR2-associated DRB1 gene in a family.
AB  - HLA-DR51 haplotypes co-express one DRB1 (B1*15 or B1*16) gene and one DRB5 gene.
      These haplotypes also carry two pseudogenes (DRB6 and DRB9) During routine HLA
      typing for transplantation, we observed an unexpected DR51 haplotype in two
      subjects (mother and daughter) in a family. Serological typing showed that these
      subjects are positive for DR51 and DQ6 but negative for DR15 and DR16.
      Investigations of genomic DNA by molecular techniques showed that these
      individuals carry DRB5*0101, DRB6*02 and DQB1*0602 genes, whereas the DRB1 gene
      associated with either DR15 (B1*1501 to B1*1504) or DR16 (B1*1601 to B1*1606) was
      not detected in the mother and daughter. It is possible that the new haplotype,
      DQB1*0602, DRB6*02, DRB5*0101, arose by deletion of DR2-associated DRB1 gene.

PMID- 9243765
TI  - Identification of new DRB1*01 (DRB1*01022), DRB1*14 (DRB1*1428) and DRB3*
      (DRB3*0206) alleles.

PMID- 9243766
TI  - A novel variant of DR11 (DRB1*1128) identified in the family by polymerase chain
      reaction-reverse dot blot.

PMID- 9243767
TI  - Identification by polymerase chain reaction and hybridization with sequence
      specific oligoprobes and complete exon-2 cDNA sequencing of a new DRB1
      (DRB1*1131) allele.
AB  - HLA-DRB1 is the most polymorphic gene described so far, and their encoded
      molecules disclose a major role in allogeneic responses. We describe in this
      report a new DRB1 allele in a Spanish Caucasian bone marrow donor, initially
      defined by PCR-SSO as a DRB1*11-like allele. Complete exon 2 cDNA-sequencing
      reveled that this allele was identical to DRB1*1119 except for a single
      substitution at position 178, which generates an amino acid change (Tyr-His) at
      position 60. This residue is shared by several DRB1*14 subtypes and DRB1*0808.
      The new allele was officially named DRB1*1131.

PMID- 9243768
TI  - High resolution HLA-C typing by PCR-SSP: identification of allelic frequencies
      and linkage disequilibria in 604 unrelated random UK Caucasoids and a comparison
      with serology.
AB  - Recent evidence indicates that HLA-C molecules are biologically relevant by
      eliciting T-cell responses and exerting control over NK cell function. In
      addition, HLA-C is associated with susceptibility to various diseases, notably
      psoriasis vulgaris. Clarification of the full biological roles for HLA-C has
      however proved difficult because detection of HLA-C antigens by complement
      mediated cytotoxicity using alloantisera is inefficient. Up to 50% of individuals
      in every race have serologically undetectable HLA-C locus antigens due to a
      combination of relatively low expression, lack of serological reagents and a lack
      of information about the distribution of the HLA-C blank alleles. Recently,
      amplification of DNA using sequence-specific primers (PCR-SSP) has proved a
      reliable, accurate and rapid method for medium resolution HLA-C typing. We have
      now developed high resolution HLA-C typing by PCR-SSP utilizing allele and group
      specific PCR-SSP reactions which can identify all HLA-C alleles (except non
      coding change alleles) in most heterozygous combinations. Using this system we
      have typed 604 unrelated United Kingdom Caucasoids to generate accurate frequency
      and linkage disequilibrium data. To assess the validity of serology for HLA-C,
      PCR-SSP typings for 527 out of the 604 individuals were compared to serology. We
      find that the frequency of many HLA-C antigens has been underestimated by
      serology and some antigens such as Cw6 are consistently assigned incorrectly by
      serology. The overall discrepancy rate between serology and SSP was high at 37%
      (195/527). High-resolution HLA-C typing of 112 International Histocompatibility
      Workshop cell lines has also been performed.

PMID- 9243769
TI  - The incidence/window period model and its use to assess the risk of transfusion
      transmitted human immunodeficiency virus and hepatitis C virus infection.

PMID- 9243770
TI  - The clinical relevance of HTLV type I and II in transfusion medicine.

PMID- 9243771
TI  - A proposal for an individual patient data based meta-analysis of randomized
      controlled trials of allogeneic transfusion and postoperative bacterial
      infection.

PMID- 9243772
TI  - The effects of managed care on transfusion medicine.

PMID- 9243773
TI  - The evolution of transfusion medicine as a stand alone discipline.

PMID- 9243774
TI  - Concepts and techniques in molecular biology--an overview.

PMID- 9243775
TI  - Parameters of cell freezing: implications for the cryopreservation of stem cells.
AB  - The overall objective of this review has been to discuss specific parameters that
      may influence the ability to successfully cryopreserve stem cells and, more
      importantly, stem-cell-based therapies. This discussion of factors is in no way
      complete. Specifically, the effect of temperature and the duration of storage,
      sensitivities to cryopreservation of bone marrow cells from patients with
      specific disorders (for example, chronic myelogenous leukemia), and the
      postfreeze processing of cells are factors of clinical significance that, for the
      sake of brevity, have been omitted. As new stem-cell-based therapies (gene, stem
      cell transplant, or immunotherapy) become the standard of care for a wide variety
      of diseases, appropriate cryopreservation protocols will be necessary to increase
      patient access, reduce cost, and enhance the safety and effectiveness of these
      therapies. Appropriate protocols must include methods and reagents appropriate
      for human use. The cryopreservation protocols developed must also reflect the
      biological and physical properties of the cells that can be altered significantly
      by the culture process. Finally, cryopreservation studies should be performed
      concurrently with in vitro culture studies to reduce the overall cost and time
      required for the development or validation of a cryopreservation protocol.

PMID- 9243776
TI  - A simple method for isolation of amplified copies of ribosomal DNA of Tetrahymena
      pyriformis by pulse-field gel electrophoresis.

PMID- 9243777
TI  - Osteoarthritis. Joint anatomy, physiology, and pathobiology.
AB  - Normal cartilage is a complex material consisting of a solid matrix composed
      primarily of collagen and proteoglycan, which is saturated with water. It is not
      a homogenous material. The interaction of the physical and biochemical structures
      of cartilage is necessary to allow the normal function of providing nearly
      frictionless motion, wear resistance, joint congruence, and transmission of load
      to subchondral bone. Chondrocytes are responsible for synthesizing and
      maintaining this material. Osteoarthritis occurs when there is disruption of
      normal cartilage structure and homeostasis. Osteoarthritis results from a complex
      interaction of biochemical and biomechanical factors that occur concurrently and
      serve to perpetuate degradative change. The progressive pathologic change that
      occurs in osteoarthritis has been characterized, not only for articular cartilage
      but also for periarticular tissues. The occurrence of mechanical and biochemical
      changes is well established, but the role of each in the etiopathogenesis of
      osteoarthritis is not rigidly defined. It is likely that there are multiple
      etiologies sharing common pathways of physical and chemical disruption. (see Fig.
      1). The changes associated with osteoarthritis ultimately have an impact on the
      patient through decreased ability to use the joint or the production of pain, or
      both. Unfortunately, once these changes are severe enough to be recognized
      clinically, they are likely to be irreversible with current treatments.
      Nevertheless, understanding the basic mechanisms involved in the development and
      progression of osteoarthritis provides a basis for establishing a reasonable
      expectation for the patient and a rational plan for medical and surgical
      treatment of this condition.

PMID- 9243778
TI  - Clinical evaluation of the osteoarthritic patient.
AB  - Clinical evaluation of the osteoarthritic patient involves critical evaluation
      off the animal and associated medical history. The most useful diagnostic aids in
      veterinary practice include joint palpation, radiography, and arthrocentesis.
      Accurate patient assessment provides diagnostic and prognostic information as
      well as serving as a baseline for medical or surgical therapies.

PMID- 9243779
TI  - Congenital conditions that lead to osteoarthritis in the dog.
AB  - Several congenital arthropathies exist in the canine that can lead to the
      development of degenerative joint disease. Nevertheless, early diagnosis and
      treatment generally will afford the patient a favorable prognosis for limb
      function. There is still a great need to develop controlled studies to evaluate
      the long-term efficacy of many of the surgical and medical treatment modalities
      that are currently available and will be made available in the future to treat
      the patient with a congenital arthropathy.

PMID- 9243780
TI  - Acquired conditions that lead to osteoarthritis in the dog.
AB  - There are many acquired arthopathies that will result in some degree of
      osteoarthritis, even after proper management. Once the articular cartilage is
      damaged, it is unlikely that the architecture of the original cartilage surface
      will return to the normal conditions that existed prior to injury. The purpose of
      timely and meticulous management of traumatic joint events is to stop the
      progression of osteoarthritic development. When dealing with articular fractures
      or other forms of trauma to articular cartilage, three important principles to
      remember are anatomic reduction of the articular surfaces, stable fixation, and
      limited weight bearing on the affected limb as soon as possible after surgery.
      Even after strict adherence to these principles, the pet owner should always be
      warned that the animal will develop some degree of osteoarthritis in the affected
      joint at some future time; at that time, chronic medical management may be
      indicated.

PMID- 9243781
TI  - Diagnostic imaging of osteoarthritis.
AB  - Osteoarthritis is a common orthopedic problem in the small animal patient. In
      most cases, the degenerative changes in the joint are secondary to some
      predisposing cause. The objective of diagnostic imaging is to define the extent
      and nature of the degenerative changes and to identify the responsible underlying
      abnormality. To achieve this, appropriate imaging procedures should be used.
      Although conventional radiography is the most common method used to evaluate
      osteoarthritis, there has been an increase in the application of other imaging
      technologies during the past several years. These modalities can provide the
      clinician with additional information that can improve case management. The
      radiographic changes that accompany osteoarthritis are reviewed, and indications
      for the various imaging modalities are outlined. The causes and presentation of
      osteoarthritis of the major diarthrodial joints of the appendicular skeleton are
      described.

PMID- 9243782
TI  - Outcome assessment in clinical trials involving medical management of
      osteoarthritis in small animals.
AB  - The goal of any clinical trial involving modulation of osteoarthritis is to
      assess the efficacy of a proposed therapy. This article attempts to provide some
      insight into assessing the outcome of clinical trials involving the management of
      osteoarthritis and reviews select key areas within clinical trials that need to
      be evaluated during critical analysis of any proposed therapeutic product.

PMID- 9243783
TI  - Kinetic and kinematic gait analysis and the assessment of lameness in the dog.
AB  - The current state of canine kinetic and kinematic gait analysis, as developed for
      the objective description of movement for the study of musculoskeletal disease
      and lameness, is reviewed. Basic terminology of gait is discussed. Ground
      reaction forces, dynamic flexion, and extension angles and angular velocities are
      described for the canine walk and trot and for lameness in cranial cruciate
      ligament rupture and canine hip dysplasia.

PMID- 9243784
TI  - Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of
      canine osteoarthritis.
AB  - Anti-inflammatory medications have long been prescribed for relief of the pain
      and discomfort associated with OA. This occurs despite the recognized side
      effects associated with use of NSAIDs and corticosteroids. Available evidence
      suggests that NSAIDs provide this relief through a combination of central and
      peripheral actions. Recent discovery of two isoforms of cyclooxygenase has
      increased our understanding of NSAID activity and may result in identification of
      drugs that potentially will have fewer side effects. A review of NSAIDs used in
      veterinary medicine indicates that relatively little is known regarding their
      role in treating OA, although controlled studies involving carprofen and etodolac
      have increased our knowledge of the efficacy of specific NSAIDs used for this
      purpose.

PMID- 9243785
TI  - Slow-acting, disease-modifying osteoarthritis agents.
AB  - There is evidence to suggest that tetracyclines have benefit beyond their
      antimicrobial activity. The ability to inhibit metalloproteinase activity may
      provide a disease-modifying effect in OA, and available data suggest that further
      investigation is warranted. Controlled, double-blind, prospective clinical
      studies have not been completed. The canine cruciate ligament transection model
      studies are frequently cited as the most convincing in vivo evidence of a benefit
      of oral tetracycline therapy for the treatment of OA. Until more evidence becomes
      available, the use of tetracyclines as therapeutic agents for OA should be
      considered investigational.

PMID- 9243787
TI  - The role of exercise and physical modalities in the treatment of osteoarthritis.
AB  - Physical rehabilitation is a valuable and often underutilized part of the overall
      management of small animals with OA. A team consisting of the veterinarian,
      physical therapist, veterinary technician, and owner is vital to determine and
      carry out an appropriate therapeutic regimen. To maintain enthusiasm for the
      program, measurements should be regularly obtained to document progress. In
      addition, controlled studies should be performed to determine the degree of
      improvement that may be expected with physical rehabilitation programs.

PMID- 9243786
TI  - Nutritional management of osteoarthritis.
AB  - Nutrition can influence developmental orthopedic diseases and the inflammatory
      process of arthritis. Developmental skeletal disease is a group of skeletal
      abnormalities that primarily affect fast-growing, large-breed dogs. Nutrient
      excesses (calcium and energy) and rapid growth (overfeeding and excess energy)
      are known risk factors. Inflammation can be directly or indirectly affected by
      nutritional influences. A direct effect can be achieved by modulating the immune
      response and inflammatory process with fatty acids. Weight control can indirectly
      influence the degenerative joint disease process by reducing the stresses on the
      joint.

PMID- 9243788
TI  - Surgical treatment of osteoarthritis.
AB  - Surgical treatment of OA is appropriate when conservative therapy fails or is
      inadequate. The veterinary orthopedist's goals in treatment should be to
      alleviate pain, maintain function, and prevent or remove the potential for
      further degeneration of the joint. Currently, in veterinary surgery, THR and
      femoral head and neck excision are the primary treatments for OA of the
      coxofemoral joint. Other joints are treated primarily by arthrodesis or excision
      arthroplasty. Arthroscopy is proving to be a valuable tool in the diagnosis and
      treatment of OA, and total stifle and elbow replacement and cartilage resurfacing
      through chondrocyte grafting are on the horizon as potential treatment options.

PMID- 9243789
TI  - Management of osteoarthritis in cats.
AB  - OA is a disease of the geriatric cat. Clinical signs include weight loss,
      anorexia, depression, urinating outside the litter box, poor grooming, and
      lameness. Radiographs, synovial fluid analysis, and synovial biopsy are used to
      distinguish this disease from the various forms of inflammatory arthritis that
      affect the cat. Management consists mainly of environmental manipulation.
      Aspirin, butorphanol, corticosteroids, and nutritional supplements are used for
      chronic treatment of painful OA in cats.

PMID- 9243790
TI  - Expression of neuroparsin cDNA in insect cells using baculovirus vectors.
AB  - The cDNA encoding neuroparsin A, a polytropic neurohormone of the locust, Locusta
      migratoria, was inserted into the genome of Autographa californica nuclear
      polyhedrosis virus such that transcription was under control of the p10 promoter.
      A polypeptide having the same charge and the same apparent molecular weight as
      the authentic neuroparsin A and that was reactive against neuroparsin immune
      serum was produced in recombinant virus-infected lepidopteran cell lines but not
      in control virus-infected cells. The baculovirus-expressed polypeptide was
      purified by two steps of liquid chromatography (anion exchange and reversed
      phase) which were previously used to purify the natural neuroparsin. The purified
      baculovirus-expressed polypeptide enhanced fluid reabsorption of everted rectum
      preparations, as did the natural neuroparsin. Thus, this gene expression system
      produced a polypeptide identical to authentic neuroparsin.

PMID- 9243791
TI  - Developmental regulation of yolk protein gene expression in Anastrepha suspensa.
AB  - A partial cDNA clone for the 48,000 dalton yolk polypeptide gene from Anastrepha
      suspensa was isolated from a cDNA expression library using a yolk polypeptide
      antibody probe and hybridization to the Drosophila melanogaster yolk protein 1
      gene. The sequenced DNA has greatest homology to the yolk protein genes from
      Ceratitis capitata, D. melanogaster, and Calliphora erythrocephala and, similar
      to these genes, shares amino acid sequence domains with those from lipases. RNA
      hybridization studies indicated that the yolk protein gene expression is
      completely female-specific and limited to the ovaries, without apparent
      regulation by 20-hydroxyecdysone or juvenile hormone. This is in contrast to an
      earlier study which suggested, based on immunological probes, that a very low
      level of yolk protein synthesis occurred in fat body and was not sex-specific.

PMID- 9243793
TI  - Light-induced vitamin deficiency in Drosophila melanogaster.
AB  - Illumination by visible light (400 Ix) of cultures containing larvae of
      Drosophila melanogaster can reduce survival (Bruins et al., Insect Biochemistry
      21:535-539, 1991). Here we show that the effect of light depends on the presence
      of propionic or acetic acid in the food medium. We also show that survival is far
      more affected by illumination of the yeast food media than by direct illumination
      of the eggs and developing larvae. It is shown that addition of antioxidants to
      the food prevents light induced mortality. The action of antioxidants suggests
      that free radicals are important in light induced mortality. We also showed that
      both yeast and riboflavin (vitamin B2) solutions illuminated with visible light
      (400 Ix) generate hydrogen peroxide. Other vitamin and amino acid solutions do
      not produce peroxide in measurable amounts. However, the concentration of
      photogenerated hydrogen peroxide is far too low to explain the death of eggs and
      developing larvae upon exposure to light. A 400 Ix light treatment destroys the
      capability of yeast food media to support survival of larvae. Addition of vitamin
      C, carotene, tryptophan, nipagin, uric acid, or sucrose to the light treated
      medium does not restore viability. It is restored when riboflavin is added to the
      photo-inactivated yeast. A high concentration of pyridoxine also produced an
      improvement in survival. When riboflavin is treated with light, it cannot support
      survival on synthetic food media nor can it restore survival on light treated
      yeast food media. These results show that riboflavin (or a derivative) is a major
      light sensitive compound of yeast, which can be degraded by light. Light induced
      loss of riboflavin leads to mortality, because this is an essential dietary
      vitamin. The vitamin degradation can be prevented by dietary antioxidants. A
      chromatographic analysis confirms this conclusion.

PMID- 9243792
TI  - Naturally occurring analogs of Lymantria testis ecdysiotropin, a gonadotropin
      isolated from brains of Lymantria dispar pupae.
AB  - Lymantria testis ecdysiotropin (LTE) was isolated from the most prominent peptide
      peak corresponding to an active fraction obtained by high pressure liquid
      chromatographic (HPLC) separation of a homogenate of 13,000 Lymantria dispar
      pupal brains. In this work we examined the other active fractions from this
      separation as well as a second HPLC separation of an additional 2,300 pupal
      brains. Bioassay of the ecdysteroidogenic effects of each peak on L. dispar
      testes allowed detection of 20 peptide peaks with testis ecdysiotropic activity
      in addition to LTE. Of these, ten peptides were purified and sequenced. All of
      them were comparable to LTE in molecular weight. The amino acid sequences of five
      of the peptides were similar enough to LTE to be considered to be members of an
      LTE family. However, the other five peptides had no significant homology with LTE
      or with each other. A BLAST database search indicated LTE family homology with
      portions of inhibitory peptides such as those inhibiting cytolysis. In contrast,
      non-LTE ecdysiotropic peptides, in which undetermined residues designated X were
      assumed to be cysteine, were strikingly homologous to portions of vertebrate and
      invertebrate zinc finger peptides and to vertebrate and invertebrate virus
      proteins.

PMID- 9243794
TI  - Specific binding of inorganic mercury to Na(+)-K(+)-ATPase in rat liver plasma
      membrane and signal transduction.
AB  - Specific binding of Hg2+ to ouabain-sensitive Na(+)-K(+)-ATPase of rat liver
      plasma membrane was demonstrated with a Ka of 2.64 x 10(9) and Bmax of 1.6 nmole
      mg-1 protein. The binding of mercury to the enzyme also causes significant
      inhibition of the enzyme, which is greater than its ouabain sensitivity. In the
      cytosol Hg2+ binding to reduced glutathione (GSH) is stimulated by GSH-S
      transferase (GST), the activity of which was found to be significantly enhanced
      by 15 mM Na+ and 10 mM Hg2+. It is proposed that the transport of Hg2+ inside the
      cell takes place by increased dissociation of Hg2+ from the membrane due to
      greater avidity of Hg2+ towards cytosolar GSH binding. The GSH-Hg complex enters
      the nucleus where it dissociates to bind the metal response element (MRE) of the
      metallothionein (MT) gene to induce MT transcription.

PMID- 9243795
TI  - Identification of a copper-sensitive ascorbate peroxidase in the unicellular
      green alga Selenastrum capricornutum.
AB  - Extracts from the unicellular green alga Selenastrum capricornutum exhibit high
      superoxide dismutase activity, but only traces of catalase activity. The excess
      hydrogen peroxide (H2O2) generated by the superoxide dismutase in S.
      capricornutum may be degraded by a unique peroxidase. This peroxidase has a high
      specificity for ascorbate as its electron donor. The enzyme has an optimum pH at
      8, is insensitive to cyanide and is inhibited by oxine. Addition of low
      concentrations of copper to algal cultures stimulates the peroxidase activity
      threefold. This enzymatic system could be used as a sensitive bioindicator for
      copper in fresh water.

PMID- 9243796
TI  - Role of metal cations in the regulation of NADP-linked isocitrate dehydrogenase
      from porcine heart.
AB  - The regulatory role of divalent metal cations in the NADP-linked isocitrate
      dehydrogenase (EC 1.1.1.42) from porcine heart was analysed. Saturation curves
      with respect to the substrate threo-DS-isocitrate complexed with the metals
      including manganous, cadmium, cobaltous and zinc ions showed sigmoid
      relationships characteristic of allosteric enzymes. The Hill's interaction
      coefficients were 1.90, 1.75, 1.28 and 1.12, respectively. Saturation kinetics of
      the substrate-metal complexes including magnesium, ferrous and nickel ions
      exhibited normal hyperbolic curves with Hill's coefficients of 1. The ionic radii
      of metal cations were closely correlated with the maximal velocity, the enzyme
      affinity and the Hill's n11 values for the substrate-metal complexes. Cooperative
      interactions of metal-substrate complexes with NADP-isocitrate dehydrogenase are
      discussed in relation to the sites of the enzyme for the binding of the metal
      substrate complex.

PMID- 9243797
TI  - Uptake of 26-Al and 67-Ga into brain and other tissues of normal and
      hypotransferrinaemic mice.
AB  - Aluminium uptake from blood into tissues of control and homozygous
      hypotransferrinaemic (hpx/hpx) mice, following continuous intravenous infusion of
      26Al and 67Ga, has been compared with that of gallium, a proposed tracer for
      aluminium. 26Al uptake into tissues of control (hpx/+ and +/+) mice occurred in
      the order (expressed as a space): bone 464.7 ml 100 g-1; renal cortex 102.9 ml
      100 g-1; liver 13.0 ml 100 g-1; spleen 8.4 ml 100 g-1 and brain 0.8 ml 100 g-1.
      67Ga uptakes were similar in liver, spleen and brain, but smaller in the renal
      cortex and bone, at one-third and one-fifth of the values for 26Al, respectively.
      In the hypotransferrinaemic mice, uptake of 67Ga into all tissues was increased,
      especially in renal cortex (ninefold) and bone (twentyfold) as compared with the
      controls. Increases in 67Ga uptakes into cerebral hemisphere, cerebellum and
      brain stem of the hypotransferrinaemic mice were 3.8, 4.2 and 2.8 fold,
      respectively. 26Al uptake into tissues of the hypotransferrinaemic mice was
      similar to control values except in bone where it was three times greater. Pre
      treatment of control animals with the anti-transferrin receptor antibody, RI7
      208, enhanced 67Ga uptake in all tissues, the effect being greatest in renal
      cortex (tenfold) and bone (ninefold). 67Ga uptakes into cerebral hemisphere,
      cerebellum and brain stem in the mice pre-treated with RI7 208 were 6.4, 6 and 10
      times greater than in untreated mice, respectively. No influence of antibody on
      26AI uptake into mouse tissues was observed except in spleen where it was three
      times greater than in untreated mice. Hence, transport of aluminium and gallium
      into mouse tissues is not similar under all conditions. Non-transferrin mediated
      transport of each metal can occur into all tissues, especially in renal cortex
      and bone, where gallium may be a suitable marker for aluminium.

PMID- 9243798
TI  - Iron uptake and intracellular metal transfer in mycobacteria mediated by
      xenosiderophores.
AB  - Growth promotion was tested using M. smegmatis wild type strain, an exochelin
      deficient mutant, and M. fortuitum employing a broad variety of xenosiderophores
      including hydroxamates, catecholates and alpha-hydroxy carboxylic acids. The
      experiments revealed that utilization of siderophore-bound iron is substrate
      specific suggesting high-affinity siderophore receptor and transport systems.
      Concentration-dependent uptake of a selected xenosiderophore (fericrocin) in M.
      smegmatis showed saturation kinetics and uptake was inhibited by respiratory
      poisons. In situ Mossbauer spectroscopy of ferricrocin uptake in M. smegmatis
      indicated rapid intracellular reductive removal of the metal excluding
      intracellular ferricrocin accumulation. The ultimate intracellular iron pool is
      represented by a compound (delta = 0.43 mm s-1, delta EQ = 1.03 mm s-1) which has
      also been found in many other microorganisms and does not represent a
      bacterioferritin, cytochrome or iron-sulfur cluster. By contrast, iron uptake via
      citrate-a compound exhibiting a very low complex stability constant-involves
      ligand exchange with mycobactin. Mycobactin has merely a transient role. The
      ultimate storage compound is an E. coli-type bacterioferritin, in which over 90%
      of cellular iron is located.

PMID- 9243800
TI  - Exocytotic fusion: total or transient?

PMID- 9243799
TI  - Enhanced hydrogen peroxide sensitivity and altered stress protein expression in
      iron-starved Mycobacterium smegmatis.
AB  - Mycobactericum smegmatis ATCC 607 became iron starved and did not reach maximum
      population density when grown at an iron concentration of 0.1 microM, or less.
      Iron deficient cells were more susceptible than iron replete cells to H2O2
      killing; 9 mM H2O2 killed about 80% of the population of cultures grown at 0.05
      microM iron, while about 25 mM H2O2 was required for similar killing of cultures
      grown at 1 or 20 microM iron. In response to H2O2, iron sufficient cells produced
      major oxidative stress proteins of molecular masses of 90, 75, 65, 62, and 43 kDa
      (the 75 and 65 kDa proteins were identified as DnaK and GroEL homologs,
      respectively). Iron deficient M. smegmatis did not upregulate the DnaK and GroEL
      proteins when stressed with H2O2. Both iron deficient and iron sufficient M.
      smegmatis produced (at 48 degrees C) major heat shock proteins of molecular
      masses of 90, 75 (DnaK), 65 (GroEL), 62, 43, and 16 kDa. The stress protein
      response induced by 2 M ethanol challenge was similar to the heat shock response
      except that ethanol induced a unique 55 kDa protein and the 16 kDa heat shock
      protein was not apparent. Induction of ethanol stress proteins was identical in
      high iron and low iron cells. All of the stress agents induced expression of a 62
      kDa protein which may also be induced by iron insufficiency. The heat and ethanol
      shock responses of M. smegmatis were unchanged by iron deficiency; therefore, the
      absence of DnaK and GroEL from the response of iron starved M. smegmatis to H2O2
      may be due to a specific defect (or alteration) of the oxidative stress response
      during iron starvation.

PMID- 9243801
TI  - Alzheimer's soluble amyloid beta protein is secreted by HepG2 cells as an
      apolipoprotein.
AB  - Recently we reported that the soluble form of amyloid beta protein (sA beta) in
      normal human plasma and cerebrospinal fluid is associated with lipoprotein (LP)
      particles. In this paper we tested the sA beta secretion by cells in association
      with LP in the model of the human hepatoma HepG2 cell line. These cells secreted
      sA beta to the culture media and expressed intracellular sA beta
      immunoreactivity. Soluble A beta in the cell supernatant was detected in 200-300
      kDa LP complexes in association with apoA-I, apoJ, transthyrethin and
      phospholipids, triglycerides and free and esterified cholesterol. This was
      assessed by size exclusion HPLC, immunoprecipitation with corresponding
      antibodies and by analysis of sA beta associated metabolically-labeled lipids,
      respectively. Our results suggest that sA beta to LP association represents a
      unique mechanism, governing the normal biology of sA beta.

PMID- 9243802
TI  - Necrosis of lung epithelial cells by filarial parasitic protein via an early
      induction of c-H-ras and TNF alpha expression.
AB  - The direct interaction of filarial proteins with lung epithelial cells was
      examined to determine the possible mechanism of inducing cell death, an event
      that is observed in patients with tropical pulmonary eosinophilia. Exposure of
      lung epithelial cells to filarial parasitic proteins, Brugia malayi (BmA),
      Setaria digitata (Sd), and recombinant filarial protein (pGT 7) in vitro for more
      than 2 days, causes the appearance of DNA fragments both in the cytoplasm and
      culture supernatants, while no fragmentation was observed in the untreated
      controls. The release of DNA fragments both in the cytoplasm and the culture
      supernatants simultaneously, indicates that cell death is induced by a necrotic
      event rather than apoptosis. Fluorescent-labelled studies also indicate the
      fragmentation of DNA increasing in a time-dependent manner. Normal cellular
      function is controlled through several oncogenes. The modulation of specific
      proto-oncogenes like myc, ras and TNF alpha during exposure to filarial parasitic
      proteins reveal elevated levels of expression of ras and TNF alpha as early as 2
      hours, implicating their involvement prior to DNA fragmentation leading to
      pathogenesis.

PMID- 9243803
TI  - Comparison of the effect of different short chain fatty acids on the growth and
      differentiation of human colonic carcinoma cell lines in vitro.
AB  - The aim of this study was to compare the effects of acetate, propionate,
      butyrate, iso-butyrate, valerate, iso-valerate and caproate on cell growth and on
      the activities of alkaline phosphatase (AP) and dipeptidyl aminopeptidase IV (DPP
      IV) by three human colonic adenocarcinoma cell lines. In addition to butyrate,
      propionate and valerate inhibited cell proliferation of the three cell lines. The
      other SCFAs did not influence cell proliferation. AP and DPP IV activities were
      strongly stimulated by butyrate on two of the three cell lines. On HT-29, AP was
      strongly stimulated, however DPPIV expression remained undetectable. Propionate
      and valerate exhibited a weaker stimulation, the other SCFAs being ineffective.
      The effect of SCFAs on cell proliferation and differentiation clearly depends on
      the number of carbons and on the configuration of the basic structure of the
      molecule.

PMID- 9243804
TI  - Time- and concentration-dependence of the growth-promoting activity of insulin
      and histamine in Tetrahymena. Application of the MTT-method for the determination
      of cell proliferation in a protozoan model.
AB  - The unicellular ciliate Tetrahymena pyriformis was treated with different
      concentrations of insulin or histamine and at different time points the cell
      density was measured, using a tetrazolium-based semiautomated colorimetric assay
      (MTT). The assay was suitable to determine the rate of cell proliferation of
      Tetrahymena. Insulin in each concentration significantly elevated the cell count
      up to 3 h. After that, it was neutral or its effect was insignificant. Histamine
      at 10(-5) M concentration diminished cell count at 3, 5, 7 and 24 h. At 10(-6) M
      concentration there was no difference and at 10(-7) M concentration it enhanced
      cell division up to 5 h, after that there being no difference. The two hormones
      have cell division promoting activity for cells of higher animals and the
      experiments demonstrate this effect already at a unicellular level.

PMID- 9243805
TI  - Visualization of Golgi apparatus in methacrylate embedded conifer embryo tissue
      using the monoclonal antibody JIM 84.
AB  - Methacrylate embedding followed by resin removal has been used for the first time
      to visualize a membrane-associated antigen at the tissue level. Monoclonal
      antibody JIM 84 was used to stain the Golgi apparatus of gymnosperm (conifer)
      embryos by light microscope immunocytochemistry. Specificity of labelling was
      confirmed by electron microscope immunocytochemistry using LR-white resin. GA
      staining was evident in all stages of white spruce somatic embryo development
      from immature to mature. Some regions of the somatic embryos (e.g. root
      cap/suspensor region) stained more vigorously than other regions
      (hypocotyl/cotyledon end). GA also stained in roots of Monterey pine and Douglas
      fir. Unlike the situation in most angiosperms, JIM 84 antigen appears to be
      absent from the conifer plasma membrane. However, it appears to be present in
      representatives of both major classes of higher plants.

PMID- 9243806
TI  - Treatment of rat proximal and distal colonic cells with sodium orthovanadate
      enhances their adhesion and survival in primary culture.
AB  - We have studied the effect of sodium orthovanadate, an inhibitor of protein
      tyrosine phosphatases, on primary cultures of colonocytes and stromal cells.
      Everted proximal and distal colonic tissue of adult rats were disintegrated by a
      collagenase/dispase solution for 60 min at 37 degrees C to prepare viable gland
      fragments and isolated cells. Cell preparations were inoculated onto plastic
      substratum or cytodex-3 microcarriers in a defined maintenance medium or in 1%
      fetal calf serum media. Incorporation of sodium orthovanadate (> or = 50 microM)
      in these media constantly enhanced the survival (cell enumeration and trypan blue
      exclusion P < 0.05) and the adhesion (up to four-fold by crystal violet staining,
      P < 0.01) of colonocytes (characterized by cytokeratin-18, transforming growth
      factor-alpha or alkaline phosphatase expression) and stromal cells. Removal of
      sodium orthovanadate from culture media restored cellular death processes.
      Incorporation of 10 mM n-butyric acid did not promote cell adhesion and survival
      except for distal cells exposed to 2 mM sodium orthovanadate. Besides studies in
      the regulation of anoikis in primary culture, the model will help to assay the
      influences of dietary and growth factors on the biology of non-cancerous colonic
      cells.

PMID- 9243807
TI  - Cell surface localization of the 60 kDa heat shock chaperonin protein (hsp60) in
      mammalian cells.
AB  - To investigate whether the 60-kDa heat shock chaperonin protein (hsp60) is
      present on the surface of mammalian cells, we used immunogold labeling of intact
      cells and backscattered electron imaging to image gold particles. Chinese hamster
      ovary cells and the human leukemic CD4-positive T-cell line CEM-SS on glass
      coverslips were labeled using affinity-purified monoclonal and polyclonal
      antibodies specific for hsp60 and 30 nm gold markers. Cells were imaged using the
      scanning mode of the conventional transmission electron microscope. Backscattered
      electron imaging provided definitive identification of the gold markers while
      secondary electron imaging gave information on surface architecture. Labeling
      intensity was 250-800 gold particles per cell in Chinese hamster ovary cells and
      600-2000 in CEM-SS human lymphoblasts. The finding of hsp60 on the cell surface
      of mammalian cells may signify chaperone involvement in surface functions.

PMID- 9243808
TI  - Lipopolysaccharide and cytokines enhance bradykinin-stimulated production of PGI2
      by cultured human pulmonary artery smooth muscle cells.
AB  - We have examined the bradykinin (BK)-stimulated production of prostacyclin (PGI2)
      by cultured human pulmonary artery smooth muscle cells (HPASMC) pretreated with
      lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor
      alpha (TNF alpha) or interferon gamma (IFN gamma). BK from 0.01 to 1 microM
      induced a dose-dependent increase in PGI2 production by HPASMC. A striking
      increase in PGI2 production in response to BK was observed in HPASMC which had
      been incubated with 1 microgram/ml LPS, 20 U/ml IL-1 beta, 50 U/ml TNF alpha or
      100 U/ml IFN gamma. After incubation with various concentrations of LPS or
      cytokines, the production of PGI2 by BK-stimulated HPASMC showed significant,
      dose-dependent increases beginning at 0.1 microgram/ml of LPS, 2 U/ml of IL-1
      beta and 5 U/ml of TNF alpha, while higher concentrations of IFN gamma failed to
      cause any further increase in PGI2 production. Our results indicate that BK is a
      potent agonist to stimulate HPASMC to produce PGI2. LPS, IL-1 beta and TNF alpha
      effectively enhanced BK-stimulated production of PGI2 by HPASMC, while IFN gamma
      had only a weak effect on BK-stimulated PGI2 production. Bradykinin-induced
      enhancement of PGI2 production by LPS, IL-1 beta and TNF alpha might be involved
      in the regulation of pulmonary vascular tension and prevent a paradoxical
      thrombogenic effect in endotoxin- or cytokine-mediated inflammation and acute
      lung injury. These experimental results suggest that vascular smooth muscle cells
      might actively control the vascular tension and blood supply by producing PGI2 in
      response to an agonist such as BK.

PMID- 9243809
TI  - Peripheral chemosensitivity and central integration: neuroplasticity of
      catecholaminergic cells under hypoxia.
AB  - The plasticity of catecholaminergic cells within the carotid body, brainstem and
      sympatho-adrenal system was analyzed in rats subjected to normobaric hypoxia (10%
      O2) lasting up to 3 weeks. Long-term hypoxia elicited structural, neurochemical
      and phenotypic changes in carotid body and sympathetic ganglia (SIF cells), and
      stimulated the norepinephrine turnover in A2 neurons located caudal to the obex,
      the area where the chemosensory nerve fibers end. Chemodenervation abolished
      central alterations. Adaptive mechanisms for increasing norepinephrine
      biosynthesis in hypoxia involved changes in activity of pre-existing tyrosine
      hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, and
      induction of new tyrosine hydroxylase protein. These neurochemical changes
      occurred after sustained hypoxia only, suggesting that noradrenergic neurons are
      involved in the central chemoreceptor pathway during sustained hypoxia but are
      not essential for regulatory responses to acute hypoxia. Acute hypoxia elicited
      the expression of c-Fos protein in neurons located in nucleus tractus solitarius
      that were not catecholaminergic. Noradrenaline released under long-term hypoxia
      could play a neuromodulatory role in ventilatory acclimatization. Cardiovascular
      responses to hypoxia are mediated by changes in sympatho-adrenal outflow,
      different according to the target organ. Cardiac sympathetic output and adrenal
      secretion were stimulated independently of carotid body chemoafferents. Early
      postnatal hypoxia induced long-term neurochemical changes in carotid body,
      brainstem and sympathetic efferents that may reveal alterations in development of
      neurons involved in the chemoreceptor pathway.

PMID- 9243810
TI  - Oxygen sensors in the organism: examples of regulation under altitude hypoxia in
      mammals.
AB  - Oxygen sensing is a determinant function of mammals, especially humans, to
      maintain their activity under acute or chronic exposure to hypoxia. True O2
      sensors (chemoreceptors, erythropoietin secreting cells) are involved in
      regulation loops, which aim to restore O2 availability to the cells. Pseudo O2
      sensors are cells activated by the lack of oxygen but not clearly involved in
      regulation processes. Potassium channels in the carotid bodies have been
      suspected to be O2 sensitive and could mediate the chemosensitivity to hypoxia.
      Na,K-ATPase related ion transport in alveolar pneumocytes could be sensitive to
      O2 availability and regulate the flux of water and sodium in the alveolar space.
      Signal transduction in G-protein-dependent receptor systems is modified in
      hypoxia, such as in cardiac beta-receptors and adenosinergic and muscarinic
      receptors. Recent studies have provided some evidence to the possible role of
      hypoxia inducible factors (HIF-1) in the regulation of protein synthesis at the
      transcriptional level. Similarities between O2-sensing mechanisms in
      erythropoiesis and in the synthesis of vascular endothelial growth factor were
      recently evidenced. Both genes are upregulated in hypoxia. However, the precise
      structure (heme-linked enzyme?) of all these O2-sensitive sites is not known,
      either in the erythropoietic system or in the chemoreceptor function. An adequate
      balance between hypoxia-induced upregulation and downregulation processes is
      necessary for optimal survival in a hypoxic environment.

PMID- 9243811
TI  - Functional consequences of acute and chronic hypoxia on respiratory and skeletal
      muscles in mammals.
AB  - Reduced oxygen supply to contracting muscles affects not only the metabolic paths
      but also modifies the gain of sensorimotor reflex loops initiated from the
      activation of specialized nervous endings that detect the changes in muscle
      metabolism and membrane outflow of potassium. Large differences are found between
      skeletal muscles and the diaphragm with respect to their sensitivity to acute or
      chronic hypoxia. The diaphragm tolerates much more hypoxemia than do skeletal
      muscles, namely those constituted by a large proportion of slow twitch oxidative
      fibers. Acute hypoxemia or ischemia accentuates the inhibitory influences exerted
      by the afferent paths from muscle metaboreceptors. This adaptative response may
      be responsible for enhanced muscle wisdom phenomenon during fatiguing
      contractions under hypoxic conditions. Prolonged and severe chronic hypoxemia
      markedly reduces muscle force generation by skeletal muscles and their endurance
      to fatigue. Restoration of normal PaO2 levels in these individuals immediately
      improves maximal muscle performance, perhaps through more efficient excitation
      contraction coupling. Recent data on the consequences of hypoxia on muscle
      metabolism and the associated changes in sensorimotor control strongly suggest
      that local acidosis cannot entirely explain all electromyogram changes found
      during and after fatiguing exercise.

PMID- 9243812
TI  - Oxygen sensing and signal transduction in metabolic defense against hypoxia:
      lessons from vertebrate facultative anaerobes.
AB  - Earlier studies identified two main defense strategies against hypoxia in hypoxia
      tolerant animals: (1) reduction in energy turnover, and (2) improved energetic
      efficiency of those metabolic processes that remain. We used two model systems
      from the highly anoxia-tolerant aquatic turtle: (1) tissue slices of brain cortex
      (to probe cell level electrophysiological responses to oxygen limitation), and
      (2) isolated liver hepatocytes (to probe signalling and defense). In the latter,
      a cascade of processes underpinning hypoxia defense begins with an oxygen sensor
      that is probably a heme protein and a signal transduction pathway that leads to
      the specific activation of some genes (increased expression of several proteins)
      and to specific down-regulation of other genes (decreased expression of several
      other proteins). The pathway seems to have characteristics in common with oxygen
      regulated control elements in other cells. The probable roles of the oxygen
      sensing and signal transduction system include coordinate down-regulation of
      energy demand and energy supply pathways in metabolism. Because of this
      coordination, hypoxia tolerant cells stay in energy balance even as they down
      regulate to extremely low levels of ATP turnover. The main ATP-demanding
      processes in normoxia (protein synthesis, protein degradation, glucose synthesis,
      urea synthesis and maintenance of electrochemical gradients) are all turned down
      to variable degrees during anoxia or extreme hypoxia. Most striking is the
      observation that ion pumping is the main energy sink in anoxia-despite reductions
      in cell membrane permeability ("channel arrest"). Neurons also show a much lower
      permeability than do homologous mammalian cells but, in this case under acute
      anoxia, there is no further change in cell membrane conductivity. We consider
      that, through this recent work, it is becoming evident how normoxic maintenance
      ATP turnover rates can be down-regulated by an order of magnitude or more-to a
      new hypometabolic steady state that is prerequisite for surviving prolonged
      hypoxia or anoxia. The implications of these developments extend to many facets
      of biology and medicine.

PMID- 9243813
TI  - Evolutionary physiology: history, principles.
AB  - 1) The history of comparative and evolutionary physiology since the early XIX
      century is given; 2) The methods of evolutionary physiology are described; 3)
      Principles of the evolution of function are discussed at every level of
      physiological organization (cellular, functional units of the organ, the organ
      itself, functional systems) as they apply to the kidney and to the regulation of
      salt and water balance; and 4) General questions of evolutionary physiology
      covering physico-chemical factors in evolution of functions, the development of
      the integrity of an organism, the origin of physiological adaptation, the
      development of interconnection of physiological systems are discussed.

PMID- 9243814
TI  - A major second messenger mediator of Electrophorus electricus electric tissue is
      CaM kinase II.
AB  - Electric tissue of the electric eel, Electrophorus electricus, has been used
      extensively as a model system for the study of excitable membrane biochemistry
      and electrophysiology. Membrane receptors, ion channels, and ATPases utilized by
      electrocytes are conserved in mammalian neurons and myocytes. In this study, we
      show that Ca2+ predominates as the major mediator of electric tissue
      phosphorylation relative to cyclic AMP and cyclic GMP-induced phosphorylation.
      Mastoparan, a calmodulin inhibitor peptide, and a peptide corresponding to the
      pseudosubstrate region of mammalian calmodulin-dependent protein kinase II
      (CaMKII (281-302)) attenuated Ca(2+)-dependent phosphorylation in a dose
      dependent manner. These experiments demonstrated that calmodulin-dependent
      protein kinase II activity predominates in electric tissue. The Electrophorus
      kinase was purified by a novel affinity chromatography procedure utilizing
      Ca2+/calmodulin-dependent binding to the CaMKII (281-302) peptide coupled to
      Sepharose. The purified 51 kDa calmodulin-dependent protein kinase II
      demonstrated extensive autophosphorylation and exhibited a 3- to 4-fold increase
      in Ca(2+)-independent activity following autophosphorylation. Immunofluorescent
      localization experiments demonstrated calmodulin to be abundant in electrocytes,
      particularly subjacent to the plasma membrane. Calmodulin-dependent protein
      kinase II had a punctate distribution indicating that it may be compartmentalized
      by association with vesicles or the cytoskeleton. As the primary mediator of
      phosphorylation within electric tissue, CaM kinase II may be critical for the
      regulation of the specialized electrophysiological function of electrocytes.

PMID- 9243815
TI  - Comparative aspects of glucose tolerance in camels, sheep, and ponies.
AB  - The aim of the study was to gain informations about factors responsible for the
      higher level of plasma glucose in camels as compared to sheep and ponies. An
      intravenous glucose tolerance test was carried out with four camels, four ponies,
      and four sheep by infusing 1 mmol glucose per kg body weight intravenously within
      3 min. Concentrations of glucose, insulin, and non-esterified fatty acids (NEFA)
      were estimated in venous plasma samples taken before and within 6 hr after
      infusion. Basal glucose values were higher in camels (7.1 +/- 0.3 mmol/l) than in
      ponies (4.2 +/- 0.4 mmol/l) and sheep (3.4 +/- 0.2 mmol/l). The rate of glucose
      elimination was markedly lower in camels (0.270 +/- 0.018 hr-1) than in sheep
      (0.804 +/- 0.036 hr-1) and ponies (0.858 +/- 0.084 hr-1). The insulin response
      after glucose infusion was more pronounced in ponies and sheep than in camels.
      Concentrations of NEFA in plasma dropped 30 min after the infusion in all
      species, however, NEFA level decreased slower in camels than in sheep and ponies.
      It is concluded that the markedly higher plasma concentration of glucose in
      camels compared to sheep and ponies may be caused by a poorer insulin response
      and/or a reduced tissue sensitivity to insulin.

PMID- 9243816
TI  - Calcium homeostasis and yeast phagocytosis in hemocytes of the colonial ascidian
      Botryllus schlosseri.
AB  - This paper reports the effects of drugs affecting the homeostasis of cytosolic
      free calcium on in vitro yeast phagocytosis by hemocytes of the colonial ascidian
      Botryllus schlosseri. Significant inhibition of phagocytosis is observed after
      exposure of hemocytes to 10 microM or higher concentrations of thimerosal, which
      is known to deplete intracellular calcium stores in mammalian cells. The two
      calcium channel blockers nifedipine and verapamil significantly decrease the
      phagocytic index, the minimum effective concentrations being 10 and 50 microM,
      respectively. As these substances have no effects at lower concentrations, they
      probably act through the inhibition of Ca(2+)-ATPase activity, required to
      restock intracellular calcium stores, due to their interaction with calmodulin.
      Analogously, pimozide, which suppresses ATPase activity by interacting with
      calmodulin, and thapsigargin, which inhibits Ca(2+)-ATPase activity,
      significantly reduce the phagocytic index. Moreover, nifedipine, by altering
      cytosolic calcium homeostasis, also lowers the production of superoxide anion
      associated with phagocytosis. Results indicate that in ascidians, as in mammals,
      a rise in intracellular calcium is required for phagocyte activation and
      induction of the respiratory burst.

PMID- 9243817
TI  - Age influence on intestinal taurine transport in mice.
AB  - Taurine plays a role in neurologic development and neuromuscular function. The
      high need for taurine during development, and the low capacity for endogenous
      biosynthesis make its intestinal handling very important. In this in vitro study,
      we investigated the uptake of taurine by intestinal strips obtained from adult,
      10-day and 20-day-old mice. Intestinal strips from adult, 10-day and 20-day-old
      mice accumulated taurine against a concentration gradient. Moreover, the capacity
      of the intestinal cells to concentrate taurine decreased with age. A major
      component of the transport process was carrier-mediated and Na-dependent.
      Analysis of the kinetics of taurine uptake revealed that Vmax decreased as the
      animals grow older without a significant change in apparent Kt. It is concluded
      that as mice grow older their intestinal capacity to absorb taurine decreases.

PMID- 9243818
TI  - High levels of ferritin and its iron in fetal bovine serum.
AB  - In 13 lots of the commercial fetal bovine sera, the ferritin levels ranged
      between 0.8 and 6.0 micrograms/ml. The serum ferritin iron concentration as
      measured by a quantitative immunoprecipitation technique ranged from 0.16 to 0.96
      microgram/ml, and the iron content of ferritin was about 20% regardless of its
      protein concentration in sera. The percentage of ferritin iron to total serum
      iron ranged from 8.8 to 28.5%, and correlated significantly with ferritin
      concentration (r = 0.9368, P < 0.001). No significant proportion of the ferritin
      in fetal serum bound to concanavalin A. Immunoblotting showed that the molecular
      weights of L(iver)- and H(eart)-type subunits of fetal serum ferritin were
      identical to those of L and H subunits of adult bovine spleen ferritin (L:21kDa,
      H:18kDa), respectively, and that the L subunit predominated in the serum protein.
      Serum transferrin level was relatively constant (1.8-2.2 mg/ml), whereas
      transferrin saturation varied from 54.8 to 91.7%. There was a significant
      correlation between serum ferritin concentration and transferrin saturation (r =
      0.8864, P < 0.001). These findings demonstrate that the bovine fetuses have the
      elevated iron stores.

PMID- 9243819
TI  - Quantification of actively transcribing RNA polymerase B molecules in human sperm
      chromatin and the effect of prostaglandin E1.
AB  - Run-on transcription experiments with sonicated chromatin from spermatozoa of
      healthy men revealed the presence of in vitro transcription. The number of
      actively transcribing RNA polymerase B molecules in sperm chromatin in vitro,
      isolated from healthy individuals, and the effect of prostaglandin El, were
      investigated. The results indicate that the number of RNA polymerase B molecules
      actively engaged in transcription increased one and a half times when 5 units of
      prostaglandin E1 was added to the reaction mixtures. These results correlate well
      with the authors' previous findings that the incorporation of labelled uridine
      triphosphate into pre-mRNA was higher when prostaglandin E1 was added to the
      reaction mixtures in run-on transcription experiments, and when sperm chromatin
      from healthy individuals was used as a template.

PMID- 9243820
TI  - Effects of secretion inhibitors on the production of CAMP factor from
      Streptococcus agalactiae.
AB  - Investigations of exopeptide secretion with inhibitors were performed to study
      the synthesis and release of CAMP factor in drug-treated growing cells of
      Streptococcus agalactiae. Besides a reduction in cell growth, membrane-active
      substances including cerulenin and neuroactive drugs, such as procaine, dibucaine
      and atropine, increased the CAMP factor activity in culture supernatant.
      Quinacrine and phenylmethylsulphonyl fluoride, inhibitors of exopeptide-releasing
      proteases, reduced the bacterial growth, but did not affect the differential rate
      of the CAMP factor release. Polyanethole sulphonic acid, an anticoagulant
      preventing cell wall autolysis, promoted cell growth, but caused approximately
      40% reduction in the production of CAMP factor from growing cells of S.
      agalactiae.

PMID- 9243821
TI  - The impact of managed care on genetic testing laboratories in the United States.
AB  - The traditional activities of clinical genetics programmes have focused on
      service, education and research. These activities have been funded on a fee-for
      service basis often supplemented by service and research grants from private and
      government sources. Developing changes in health care financing threaten this
      approach to funding of genetics programmes in general and of genetics
      laboratories in particular. The evolution of managed health care requires new
      strategies for delivery of clinical and laboratory services with an emphasis on
      adaptability. Strategies may include development of alliances among related
      laboratories, subcontracting with large, multiservice laboratories and developing
      formalized marketing plans.

PMID- 9243822
TI  - The role of platelet-derived growth factor in turkey skeletal muscle development.
AB  - The role of platelet-derived growth factor (PDGF) isoforms in the proliferation
      of turkey skeletal muscle cells was examined using turkey myogenic cells. To
      compare the effects of PDGF during different developmental stages, postnatal
      myogenic satellite cell and embryonic myoblast cultures were developed for in
      vitro comparisons. Satellite cell cultures from turkeys selected and unselected
      for skeletal muscle accretion rates were also established to compare the role of
      PDGF in turkeys with different genetic origins. The results demonstrated that the
      BB and AB isoforms of PDGF enhanced satellite cell and embryonic myoblast
      proliferation, while the AA isoform had no effect. Satellite cells and embryonic
      myoblasts were more responsive to the BB isoform than to the AB isoform.
      Competitive binding assays demonstrated that there were no differences between
      PDGF receptor affinities or receptor numbers on either embryonic myoblasts and
      satellite cells or satellite cells derived from selected and unselected turkeys.
      The results suggest that PDGF may be an important mitogenic factor in turkey
      skeletal muscle development.

PMID- 9243823
TI  - Extent of heterogeneity in mitochondrial DNA of sub-Saharan African populations.
AB  - Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence
      specific oligonucleotide (SSO) probes is described for 381 individuals from nine
      sub-Saharan African populations. Population diversity estimates for SSO types
      ranged from 0.23 to 0.97, while 102 SSO types were detected, none of these types
      was shared by more than four populations. Eighteen types occurred in > or = 10%
      of individuals in some populations; of these, 11 were population-specific. One
      type occurred in 15% of the total sample, but was shared among only three
      populations. African SSO types were characterized by high frequencies of blank
      variants, indicating that there was additional variation present at the
      nucleotide sequence level in regions where SSO probes hybridize. Analyses of
      molecular variance (AMOVA) incorporating genetic distances between SSO types
      showed that 30% of the total variation was due to differences among populations,
      indicating that there is statistically significant heterogeneity (p < 0.001). An
      AMOVA on mtDNA control region nucleotide sequence data from 12 populations showed
      that including all additional variation present at the sequence level increased
      the variance due to population subdivision to 34% (p < 0.001). Overall, when
      considering both the low diversity within some populations and high heterogeneity
      among populations, SSO typing of mtDNA may not be a desirable forensic DNA typing
      method for continental African populations. Further mtDNA sampling of African
      derived populations of North America should be carried out to determine how much
      of the continental African mtDNA variation is of forensic significance. However,
      the existence of extensive mtDNA control region nucleotide sequence variation in
      African populations means that control region sequencing is still appropriate in
      forensic cases requiring mtDNA analysis.

PMID- 9243824
TI  - Sequence analysis of domestic dog mitochondrial DNA for forensic use.
AB  - A method has been developed for the direct sequencing of hypervariable region 1
      (HV1) of domestic dog (Canis familiaris) and wolf (Canis lupus) mitochondrial DNA
      (mtDNA) using single hairs as template. The method uses a robotic work-station
      and an automated sequencer to allow for robust routine analysis. A population
      data base was created in order to investigate the forensic and population-genetic
      informativeness of domestic dog HV1. Sequence variation, partitioning of dog
      breeds among sequence variants and phylogenetic relations between the variants
      were determined. Samples from 102 domestic dogs of 52 different breeds and two
      captive wolves were analyzed. Nineteen dog-sequence variants were found and the
      frequencies of the variants ranged from 1 to 21%. The calculated discrimination
      power of the region, i.e., the exclusion capacity, implied that nine out of ten
      disputed individuals can be excluded by this analysis. The sequence variants were
      found to cluster into four phylogenetic groups.

PMID- 9243825
TI  - The estimation of age of bloodstains by HPLC analysis.
AB  - A new HPLC system is described for estimating the age of bloodstains deposited on
      clothing. In addition to the decomposition peak designated as "X" and reported
      earlier in the literature, several other ageing processes were studied and found
      suitable for estimation of age of the stains. The various processes can be used
      independently of each other for estimation of bloodstain age when the storing
      temperature is known. Moreover, the ratio between the different peaks formed by
      ageing is practically independent of temperature between 0 degree C and 37
      degrees C.

PMID- 9243826
TI  - A fully three-dimensional method for facial reconstruction based on deformable
      models.
AB  - Two facial models corresponding to two deceased subjects have been manually
      created and the two corresponding skulls have been dissected and skeletonized.
      These pairs of skull/ facial data have been scanned with a CT scanner, and the
      computed geometric three-dimensional models of both skulls and facial tissue have
      been built. One set of skull/facial data will be used as a reference set whereas
      the second set is used as ground truth for validating our method. After a semi
      automatic face-skull registration, we apply an original computing global
      parametric transformation T that turns the reference skull into the skull to be
      reconstructed. This algorithm is based upon salient lines of the skull called
      crest lines: more precisely the crest lines of the first skull are matched to the
      crest lines of the second skull by an iterative closest point algorithm. Then we
      apply this algorithm to the reference face to obtain the "unknown" face to be
      reconstructed. The reliability and difficulties of this original technique are
      then discussed.

PMID- 9243827
TI  - Forensic three-dimensional facial reconstruction: historical review and
      contemporary developments.
AB  - Despite varied attempts to achieve standardization in traditional techniques and
      the promotion of some newly developed ones, facial reconstruction remains on the
      threshold between art and science. It is the point at which science ends and the
      medical illustrator takes over that has led to most reservations over this branch
      of forensic anthropology. The purpose of this paper is to demonstrate that many
      techniques of facial reconstruction are prima facie questionable and to
      illustrate some possible solutions to the problems which are currently being
      explored by the Facial Reconstruction Project at the University of Sheffield
      (UK). The review includes 15 responses to a questionnaire which was offered to
      facial reconstruction experts and related specialists. The use of 3D color laser
      scanning equipment, collection of tissue depth measurements from CT scans and the
      development of a computer system for 3D forensic facial reconstruction, are
      described.

PMID- 9243829
TI  - Stalking on campus: the prevalence and strategies for coping with stalking.
AB  - This epidemiological study explored the prevalence of stalkers and stalking
      victims among college students. Two questionnaires (one assessing the behaviors
      of those who stalk others, and the other assessing victims of stalking) were
      administered to 294 college undergraduates. The questionnaires were then revised
      and readministered to 299 undergraduates. Thirty percent of the female students
      and 17% of the males reported having been stalked; 80% reported that they knew
      their stalker (many had been previously romantically involved with the stalker).
      Only 1% of the subjects acknowledged having stalked someone, due perhaps to the
      social undesirability of this behavior. Methods of coping with being stalked were
      also assessed. The most common response among females was to ignore the stalker;
      among males it was to confront the stalker.

PMID- 9243828
TI  - Violence in America: a survey of suicide linked to homicides.
AB  - This paper describes murder-suicide in the United States from 1990 through 1995,
      using the cases reported in six major newspapers. Spousal murder-suicide was the
      predominant type with a range of 42%-57%; familicide-suicide was the second
      predominant type with a range of 22%-47%. The perpetrators were predominantly
      males; the victims were female sexual partners or consanguineous relatives.
      Firearms (guns) were used in 90% of the cases. The author concludes that a
      national surveillance system that specifically identifies and codes this
      phenomenon, and multi disciplinary studies are necessary to hinder this
      phenomenon.

PMID- 9243830
TI  - The role of mania in the genesis of dangerous delusional misidentification.
AB  - The delusional misidentification syndromes are characterized by a
      misidentification delusion of the self and/or others. Delusional
      misidentification syndromes frequently occur in psychotic disorders such as
      schizophrenia, psychotic disorder due to general medical condition, or psychotic
      disorder not otherwise specified. On rare occasions these syndromes may be
      associated with manic states secondary to bipolar disorder, schizoaffective
      disorder, or general medical conditions. The delusional misidentification
      syndromes may also be associated with verbal and physical aggression. In this
      article we present three cases of dangerous delusional misidentification
      associated with mania. We will discuss the role that mania may have in the
      genesis of dangerous delusional misidentification.

PMID- 9243831
TI  - Findings in gunshot wounds from tandem projectiles.
AB  - Tandem projectiles are unusual events which can cause erroneous case
      interpretations if one is unfamiliar with them. This paper presents two such
      cases. The first case involved three .32 caliber bullets, two of which became
      lodged in a revolver barrel because of faulty ammunition. A third fired bullet
      subsequently pushed itself and the lodged bullets out of the barrel resulting in
      a single entrance wound with three bullets in the body. The second case involved
      a 20 gauge shotgun shell which apparently was inadvertently loaded into a 12
      gauge shotgun. This resulted in an unusual entrance wound and unusual X-rays with
      fragments of the 20 gauge shotgun shell, as well as 12 gauge shotgun shell
      wadding, being removed from the same wound. The pertinent findings in such cases
      are discussed so that they may be correctly identified when they occur.

PMID- 9243832
TI  - A statistical approach to the prediction of verifiable heroin use from total
      codeine and total morphine concentrations in urine.
AB  - There has been much debate in urine drug testing over what criteria should be
      applied to total codeine and total morphine concentration data to determine the
      likelihood that a urine donor has used heroin and whether such use can be
      demonstrated by the presence of 6-acetylmorphine. After determining that the
      stability of 6-acetylmorphine in frozen urine is adequate for a period of at
      least two years, a database of over 100 codeine and/or morphine positive urine
      specimens was subjected to relative operating characteristic analysis to identify
      a criterion that would indicate a high probability of detecting 6-acetylmorphine
      in a specimen and thus confirming heroin use. A two-fold criterion was
      identified. By using a criterion that requires the total morphine concentration
      to be greater than 5.000 mg/L and the total codeine to total morphine ratio to be
      less than 0.125, one can predict the presence of 6-acetylmorphine with a
      sensitivity of 92%, a specificity of 79%, and an overall accuracy of 73%.
      Although this criterion is statistically the most accurate in terms of both
      sensitivity and specificity for the data analyzed by the author, the results of
      other, criteria are presented to aid toxicologists and medical review officers in
      determining if analysis for 6-acetylmorphine is likely to produce useful results.

PMID- 9243833
TI  - Inhibition of ethanol production by Saccharomyces cerevisiae in human blood by
      sodium fluoride.
AB  - Production of ethanol in antemortem blood samples inoculated with an efficient
      ethanol-producing microorganism and incubated at various temperatures is
      discussed. Whole blood samples inoculated with Saccharomyces cerevisiae were
      incubated in gray stoppered Venoject tubes (approximate draw volume 7 mL)
      containing sodium fluoride (17.5 mg) and potassium oxalate (14.0 mg) at 4 degrees
      C, 25 degrees C, and 37 degrees C for 0, 24, 96, 192, and 408 h. No volatile
      substances (such as ethanol, methanol, isopropanol, acetone, or acetaldehyde) (<
      0.010 g/dL) were produced in any of the samples at 4 or 25 degrees C. At 24 h
      incubation a trace amount (< 0.018 g/dL) of ethanol was detected at 37 degrees C.

PMID- 9243834
TI  - A novel derivatization of phenol after extraction from human serum using
      perfluorooctanoyl chloride for gas chromatography-mass spectrometric confirmation
      and quantification.
AB  - Phenol (carbolic acid) is widely used as a disinfectant as well as in the
      chemical industry as an intermediate in the synthesis of a variety of chemicals.
      Phenol is also the major metabolite of benzene which is used in many commercial
      solvents. Phenol is toxic and caustic and may cause death even from dermal
      absorption. Therefore, measurement of phenol in postmortem blood is essential.
      The concentration of phenol in blood can be measured by gas chromatography with
      flame ionization or mass spectrometry. Phenol can also be analyzed by high
      performance liquid chromatography. However, in forensic toxicology, unambiguous
      confirmation of phenol by mass spectrometry is as important as quantification in
      blood. Here we describe a novel derivatization of phenol after extraction with
      chloroform from human serum using perfluorooctanoyl chloride. The
      perfluorooctanoyl derivative of phenol showed a strong molecular ion at m/z 490
      (relative abundance: 23%) whereas the base peak was observed at m/z 77. The
      derivative of the internal standard 3,4-dimethylphenol showed a very strong
      molecular ion at m/z 518 (relative abundance: 56%) and the base peak was observed
      as m/z 121. The derivative of p-cresol, a chemically related phenolic compound,
      showed a strong molecular ion at 504 m/z (relative abundance: 54%) and a base
      peak at m/z 107. We observed baseline separation between derivatized phenol
      (retention time: 6.1 min), p-cresol (retention time: 7.8 min), and the internal
      standard (retention time: 9.4 min). We observed no interferences in our assay
      from grossly hemolyzed serum. Within and between run precision was studied using
      a serum standard containing 25 mg/L of phenol. The within run precision was 6.6%
      (mean = 24.3, SD = 1.6 mg/L, n = 8) whereas the between run precision was 8.6%
      (mean = 25.5, SD = 2.2 mg/L, n = 8). The assay was linear for serum phenol
      concentrations of 10-200 mg/L. The detection limit was 1 mg/L of serum phenol
      concentration. The average recoveries were 92.1% to 94.0% for various serum
      phenol concentrations.

PMID- 9243835
TI  - Gas chromatographic-mass spectrometric identification and quantitation of benzyl
      alcohol from human serum and postmortem blood after derivatization with 4
      carbethoxy hexafluorobutyryl chloride: a novel derivative.
AB  - Benzyl alcohol is commonly used as an antibacterial agent in a variety of
      pharmaceutical formulations. Several fatalities in neonates have been linked to
      benzyl alcohol poisoning. Most methods for measuring benzyl alcohol
      concentrations in serum utilize direct extraction followed by high performance
      liquid chromatography. We describe a novel derivatization of benzyl alcohol using
      4-carbethoxyhexafluorobutyryl chloride after extraction from human plasma, and
      subsequent analysis by gas chromatography-mass spectrometry (GC/MS). The
      derivative was eluted at a significantly higher temperature and the method was
      free from interferences from more volatile components in serum and hemolyzed
      specimens. However, with postmortem specimens, we observed multiple peaks which
      were eluted at a very high temperature, long after derivatized benzyl alcohol and
      the internal standard. Therefore, baking the column at 310 degrees C is
      recommended after analysis of a postmortem specimen. Another advantage of this
      derivatization technique is the conversion of low molecular weight benzyl alcohol
      (MW 108) to a high molecular weight derivative (MW 358). The positive
      identification of benzyl alcohol can be easily achieved by observing a distinct
      molecular ion at m/z 358 as well as other characteristic ions at m/z 107 and 91.
      Quantitation of benzyl alcohol in human serum can easily be achieved by using 3,4
      dimethylphenol as an internal standard. The within run and between run precisions
      (using serum standard of benzyl alcohol: 50 mg/L) were 2.2% (mean = 50.6, SD =
      1.1 mg/L), and 6.9% (mean = 50.8, SD = 3.5 mg/L). The assay was linear for the
      serum benzyl alcohol concentrations of 5 mg/L to 200 mg/L and the detection limit
      was 1 mg/L. We observed no carry-over problem in our assay as when 2 microL ethyl
      acetate was injected into the GC/MS after analyzing serum specimens containing
      200 mg/L of benzyl alcohol, we observed no peak for either benzyl alcohol or the
      internal standard in the total ion chromatogram.

PMID- 9243836
TI  - Validation studies of the CTT STR multiplex system.
AB  - Studies were performed to define the typing conditions and evaluate the forensic
      applicability of multiplex amplification of three STR loci, CSF1PO, TPOX, and
      THO1. Results were obtained using the GenePrint STR System (Promega Corporation,
      Madison, WI) Kit. To determine the utility of the GenePrint STR System for
      forensic casework analyses, the following experiments were conducted: 1) analysis
      of mixed body fluid; 2) determination of the sensitivity of detection; and 3)
      evaluation of results from biological samples from casework. In addition, the
      following simulated forensic conditions were assayed to detect whether or not
      there may be adverse effects on the ability to type these loci: 1) chemical
      contaminant effects on the DNA in body fluid samples; 2) the effects on DNA from
      samples deposited on various substrates; 3) the consequences of micro-organism
      contamination; and 4) the effect of sunlight and storage conditions on the
      integrity of the STR profiles/DNA. The data demonstrate that STR typing of
      biological samples exposed to a variety of environmental insults yields reliable
      results and that the analysis of the STR loci CSF1PO, TPOX, and THO1 can be
      applied in a forensic setting.

PMID- 9243837
TI  - The applicability of formalin-fixed and formalin fixed paraffin embedded tissues
      in forensic DNA analysis.
AB  - Historically, formalin fixed (FF) tissues could not be used as a source of DNA in
      forensic science due to the fact that the DNA was too degraded for DNA analysis.
      With the introduction of the polymerase chain reaction (PCR) technique to
      forensic science, the usefulness of DNA from this biological material has been re
      evaluated. This study evaluates the potential use of DNA from FF and formalin
      fixed paraffin embedded (FFPE) tissues in 13 PCR systems; HLA DQ alpha, LDLR,
      GYPA, HBGG, D7S8, GC, D1S80, vWA31, THO1, F13A1, FES/FPS, TPOX, and CSF1PO. The
      first six, HLA DQ alpha, LDLR, GYPA, HBGG, D7S8, and GC are reverse dot blot
      systems, D1S80 is an amplified fragment length polymorphism (AmpFlp) system and
      the others are short tandem repeats (STRs). This study shows that FFPE tissue
      which has not been fixed in formalin for more than three days is a useful source
      of DNA for 12 of the 13 PCR systems. In contrast, FF tissue did not prove to be a
      reliable source of DNA for the PCR techniques examined here.

PMID- 9243838
TI  - Rapid screening of multiple forensic stains by SSCP analysis of HLA-DQ alpha
      amplification products.
AB  - Single strand conformation polymorphism (SSCP) analysis was performed with HLA-DQ
      alpha amplification products. The various HLA-DQ alpha genotypes reveal different
      SSCP patterns. These are reproducible in DNA preparations from unrelated persons
      with identical HLA-DQ alpha genotype. However, in one of the more frequent HLA-DQ
      alpha genotypes (1.1/4) two variant SSCP patterns were observed. SSCP analysis
      allows rapid low-cost screening of many specimens and is an alternative
      discrimination test of stains beside reverse dot blot hybridization.

PMID- 9243839
TI  - DNA typing of azoospermic semen at the D1S80 locus.
AB  - The examination of azoospermic semen poses a special problem for the forensic
      scientist. Both serologic and RFLP methods may result in inconclusive results.
      PCR analysis is known to have an advantage in the evaluation of variably
      degraded, small quantities of DNA. This investigation addresses the feasibility
      of detecting the DNA profiles of azoospermic males in cases of suspected rape by
      the use of PCR amplification of the VNTR locus DIS80. DNA profiles were produced
      from aspermic semen samples from six vasectomized males. Two mixed postcoital
      vaginal samples containing azoospermic semen from two of the vasectomized males
      were also obtained and both revealed the combined profiles of the azoospermic
      semen donors and the vaginal epithelial donors. All cases resulted in an allelic
      banding pattern of the donor semen matching the respective blood/saliva standard.

PMID- 9243841
TI  - Sex determination by discriminant analysis of calcanei measurements.
AB  - Eight measurements taken on the right calcaneus (maximum length, load arm width,
      minimum width, height of calcaneus, body height, breadth of the facies
      articularis talaris posterior, breadth and height of the facies articularis
      cuboidea) of a known contemporary Southern Italian skeletal population (40 males
      and 40 females) were used to determine sex by multivariate discriminant analysis.
      Three functions revealed a correct sex-determination of 85%. These functions were
      obtained by the association of the following parameters: maximum length, load arm
      width and breadth of the facies art. talaris post. (function no. 1); maximum
      length and breadth of the facies art. talaris post. (function no. 2); maximum
      length and height of the facies art. cuboidea and breadth of the facies art.
      cuboidea (function no. 3). These results may aid the forensic anthropologist when
      no other remains, useful for skeletal sex determination, are available.

PMID- 9243840
TI  - An assessment of DNA contamination risks in New York City Medical Examiner
      facilities.
AB  - DNA evidence holds an important position in criminal investigations and
      proceedings. The polymerase chain reaction (PCR) is often utilized to amplify
      polymorphic regions of DNA which are subsequently typed to produce distinct
      genotypes. The sensitivity of PCR-based techniques provides a major advantage
      over other DNA or conventional serological typing systems. Samples containing
      quantities of DNA in the picogram range are often typed. However, the
      unprecedented sensitivity of PCR is often cited as a criticism. One concern is
      that the interpretation of PCR typing can be affected by DNA contaminants from
      foreign sources. In this report, the level of DNA contamination in New York City
      Medical Examiner facilities and its potential affects on HLA-DQA1 typing were
      assessed. Two related studies conducted over a five week period measured and
      typed HLA-DQA1 from accumulated DNA on autopsy room and Forensic DNA Laboratory
      structures. The potential for DNA contamination from airborne sources was also
      evaluated in the autopsy suites. This study demonstrated the presence of small
      amounts of DNA on structural surfaces, but little evidence of airborne DNA
      contamination.

PMID- 9243842
TI  - An unusual penetrating neck wound by a golf club: precise forensic imaging.
AB  - An unusual case of a penetrating neck injury by a golf club with the weapon
      retained in situ is presented. The contemporary imaging technology that
      delineated the clinical and forensic aspects is demonstrated as another tool to
      assist in criminal investigation.

PMID- 9243843
TI  - Distribution of free and conjugated morphine in body fluids and tissues in a
      fatal heroin overdose: is conjugated morphine stable in postmortem specimens?
AB  - The tissue distribution of free and conjugated morphine in a male individual who
      died after self-injection of heroin and methamphetamine was investigated, and the
      postmortem stability of morphine in the blood, liver and urine, and that of 6
      monoacetylmorphine in the urine was determined. Confirmation and quantitation of
      morphine, 6-monoacetylmorphine and methamphetamine were performed by gas
      chromatography/mass spectrometry and gas chromatography, respectively. Blood
      levels of free and total morphine were very site-dependent with ranges of 462
      1350 and 534-1570 ng/mL, respectively. Large amounts of total morphine, 5220,
      4200, and 2270 ng/g, had accumulated in the stomach contents, liver, and lung,
      respectively. The concentration of free morphine in the cerebrospinal fluid was
      correlated very closely with that in the cerebrum. The proportion of free
      morphine in various fluids and tissues ranged from 23.0% to 98.8% of total
      morphine: less than 30% in the stomach contents and urine; 30-60% in the liver,
      cerebrospinal fluid, lung, and pericardial sac fluid; 61-90% in the spleen, right
      femoral muscle, myocardium, blood in the left and right ventricles of the heart,
      and right femoral vein blood; more than 91% in the right kidney and cerebrum.
      Detectable amounts of 6-monoacetylmorphine, 417 ng/mL and 78 ng/g, existed in the
      urine and stomach contents, respectively, indicating that this individual might
      have died within several hours after heroin injection. Methamphetamine
      concentrations in the blood were also site-dependent within the range 551-1730
      ng/mL. In an in vitro experiment, free and conjugated morphine were stable in the
      blood and urine at 4, 18-22, and 37 degrees C for a 10-day study period. In the
      liver, however, conjugated morphine had been converted almost completely to free
      morphine at 18-22 and 37 degrees C by the end of the experiment, although it was
      stable at 4 degrees C. Urine 6-monoacetylmorphine, although degraded slightly at
      37 degrees C, was stable at 4 and 18-22 degrees C during the experiment. Thus it
      appears that non-specific hydrolysis of conjugated morphine to free morphine
      would not occur in corpses at least for a few days after death. Femoral muscle
      may be a specimen of choice for roughly predicting the ratio of free to total
      morphine in blood even when blood specimens are not available, because the
      femoral muscle is relatively spared of both postmortem diffusion of drugs and
      bacterial invasion.

PMID- 9243844
TI  - Fatal fentanyl intoxication following excessive transdermal application.
AB  - The case history and toxicological findings of a fatal fentanyl intoxication due
      to the application of multiple transdermal patches are presented. An 83 year-old
      white female with terminal cancer was found dead with three 100 mg/h fentanyl
      patches on her chest. The autopsy and subsequent histological studies revealed
      extensive areas of gastric carcinoma, a large atrial tumor, ulceration of
      esophagus, metastasis of peripancreatic lymph nodes and a recent surgical removal
      of part of the lower lobe of the left lung. Toxicological analysis by GC/MS
      yielded fentanyl concentrations of blood, 25 ng/mL; brain, 54 ng/g; heart 94
      ng/g; kidney 69 ng/g; and liver 104 ng/g. The cause of death was determined to be
      fentanyl overdose and the manner of death was ruled undetermined as the
      investigation was unable to conclusively establish whether this was an accidental
      overdose, a suicide, an assisted suicide, or possible a homicide. This case
      demonstrates the need for caution in self-administration of transdermal fentanyl
      patches, in particular, the dangers inherent in the application of multiple
      patches which can result in the release of potentially toxic or lethal doses.

PMID- 9243845
TI  - Evidence of pin implantation as a means of verifying death during the Great
      Plague of Marseilles (1722).
AB  - The evidence obtained for the methods used in verification of death during the
      Great Plague of Marseilles in 1722 is presented here. This evidence was gathered
      during the excavation of a mass grave dating from this epidemic, and is based on
      two adjacent interments. The technique used at that time was the implantation of
      bronze pins into the toes. This method is precisely described in the medical
      treatises dating from this period, which list different death verification
      methods. The fear of "false death" and the burial of still living people
      characterized the end of the 17th and the 18th centuries. It should be noted that
      the main cause of apparent death is presented in the same medical treatises as
      the plague. This observation is the first anthropological evidence of the use of
      this forensic method to verify the fact of death.

PMID- 9243846
TI  - Teratogenic effects of chlormetine hydrochloride in rats.

PMID- 9243847
TI  - Embryotoxic effects of B-193 in mouse.

PMID- 9243848
TI  - Evaluation of histopathological changes of the pancreatic tissue in the course of
      acute experimental pancreatitis.

PMID- 9243849
TI  - Differences in epinephrine levels in rat brains after administered morphine.

PMID- 9243850
TI  - Changes of hydroxyproline levels in myocardium after chronic administration of
      bleomycin.

PMID- 9243851
TI  - Ultrastructural, stereological evaluation of satellite cells derived from
      musculus soleus in rats kept in hypokinesia conditions.

PMID- 9243852
TI  - The contribution of the subclavian artery in the blood supply of the main bronchi
      in the human fetuses.

PMID- 9243853
TI  - Adrenal glands in anencephaly.

PMID- 9243854
TI  - Timing of events during embryonic development of parathyroid glands.

PMID- 9243855
TI  - Sources of the autonomic fibers to the mammary gland in pig.

PMID- 9243856
TI  - Connections between the great saphenous vein and other cutaneous veins of the
      thigh in human fetuses.

PMID- 9243857
TI  - Reticular afferents from vestibular nuclei.

PMID- 9243858
TI  - Angioarchitecture of the epididymis in men bull and ram.

PMID- 9243859
TI  - Classification, topography and morphometry of the early branches of the middle
      cerebral artery.

PMID- 9243860
TI  - Changes in selected Wistar rats lymph nodes after intratissue injection of
      allogenic blood.

PMID- 9243861
TI  - Morphometrical study of the rat liver sinusoids in chronic ethanol intoxication.

PMID- 9243862
TI  - Microsurgical anatomy of the venous system of the lateral cerebral fossa.

PMID- 9243863
TI  - Main arteries of the head and circulus arteriosus at representatives of the order
      of pinnipeds.

PMID- 9243864
TI  - Digital-image analysis of the rhomboid fossa surface.

PMID- 9243865
TI  - A new morphometrical method for measuring the diameter, length and volume of
      vessels.

PMID- 9243866
TI  - Computer-assisted image analysis of the variations in the cerebral arterial
      circle (of Willis) in human fetuses.

PMID- 9243867
TI  - Optical properties of human meniscus.

PMID- 9243868
TI  - The effects of met-enkephaline, leu-enkephaline and tuftsine on guinea pig
      peritoneal granulocyte functions in vitro.

PMID- 9243869
TI  - The effects of 4-chloro-ortho-toluidine (fast red TR) subacute intoxication on
      rats. Part I: The kidney and the urinary bladder epithelium.

PMID- 9243870
TI  - The effects of 41-chloro-ortho-toluidine (fast red TR) subacute intoxication on
      rats. Part II: The liver and the lungs.

PMID- 9243871
TI  - The effects of 4-chloro-ortho-toluidine (fast red TB) acute intoxication on rats
      and guinea pigs. Part III: The effect in vitro on viability of rat thymic and
      splenic lymphocytes, and on guinea pig granulocyte adherence, chemotaxis and
      phagocytosis.

PMID- 9243872
TI  - Unilateral testicular torsion in Lewis rats. Part I: The effect on spleen
      lymphocytes mitotic activity in vivo.

PMID- 9243874
TI  - Internal carotid artery in rostral epidural rete mirabile in animals of the
      suborder of Ruminantia.

PMID- 9243873
TI  - Unilateral testicular torsion in Lewis rats. Part II: The effect on thymocytes
      mitotic activities in vivo and some morphometric features of thyroid gland.

PMID- 9243875
TI  - Morphology of the uterine artery in human fetuses.

PMID- 9243876
TI  - Morphology of the coronary sinus and contemporary cardiac electrophysiology.

PMID- 9243877
TI  - Meninx primitiva of the spinal cord in human embryos at stage 13 (28
      postovulatory days).

PMID- 9243878
TI  - Comparative morphology of the spinal ganglia in the different segments of the
      spinal cord in sheep.

PMID- 9243879
TI  - Magnetic resonance imaging of neurovascular compression of the V-XII cranial
      nerves.

PMID- 9243880
TI  - Development of blood vessels of stomach wall in rabbits during prenatal period.

PMID- 9243881
TI  - Morphometric analysis of stomach wall organogenesis in rabbit.

PMID- 9243882
TI  - Stereological, ultrastructural analysis of Sertoli cells of male mouse embryos.

PMID- 9243883
TI  - Selected morphological features of overweighed children's foot as overload
      adaptation indices.

PMID- 9243884
TI  - Vascularization of the hip joint in the human fetuses.

PMID- 9243885
TI  - The vastus medialis longus and the vastus medialis obliquus muscles-question
      about quadriceps femoris.

PMID- 9243886
TI  - Evaluation of radial artery as used for coronary vessel grafting in human heart.

PMID- 9243887
TI  - Modern techniques in teaching of anatomy.

PMID- 9243888
TI  - Comparative study of the intratesticular vascular rete in men and certain
      animals.

PMID- 9243889
TI  - The arterial vascularisation of the human calcaneus (Achilles) tendo during the
      prenatal development.

PMID- 9243890
TI  - Age related changes in the motoneurons of the spinal cord of the rat.

PMID- 9243891
TI  - Flow cytometry in clinical diagnosis and in tests on new drugs.

PMID- 9243892
TI  - Evaluation of inferior nasal concha in fetal period with the usage of image
      computer transformation.

PMID- 9243893
TI  - Evaluation of "ELF" program usefulness in metrologic examinations of fetal brain.

PMID- 9243894
TI  - Analysis of contemporary methods of anatomical structures visualisation in Imtron
      2000 system, Image C package.

PMID- 9243895
TI  - Typology and topography of transverse and occipital sinus vascular drainage
      region in fetal period.

PMID- 9243896
TI  - On development and clinical aspects of human supratentorial bridge veins.

PMID- 9243897
TI  - Venous angioarchitecture of human cerebellum in fetal period.

PMID- 9243898
TI  - Evaluation of human dura mater resistance in MTS Mini Bionix 85802 System.

PMID- 9243899
TI  - Anatomy of the posterior communicating artery--preliminary report.

PMID- 9243900
TI  - Preliminary evaluation of the topography of the His bundle with regards to
      ablation procedures.

PMID- 9243901
TI  - Morphologic features and number of the muscle spindles in the oblique eye muscles
      of human fetuses.

PMID- 9243902
TI  - The lymphatic pathways and regional lymph nodes of the rat liver visualized of
      liposomes and fluorochrome--labelled dextran.

PMID- 9243903
TI  - Remarks on the arterial vascularization of double kidney.

PMID- 9243904
TI  - Variation of the structure and course of the interlobular arteries in human
      kidney.

PMID- 9243905
TI  - Neurons of the claustrum projecting to the motor and somatosensory cortex in the
      rabbit--assessment with the method of retrograde transport of fluorescent
      tracers.

PMID- 9243906
TI  - Morphology of the atrioventricular node in relation to the mechanism of
      atrioventricular nodal reentry tachycardia--a preliminary report.

PMID- 9243907
TI  - Ontogenetic development of claustrum in a cow.

PMID- 9243908
TI  - Children brain weight in various pathological conditions.

PMID- 9243909
TI  - Development of the urorectal septum and differentiation of the urogenital sinus
      in human embryos of stages 13 to 19.

PMID- 9243910
TI  - Electron microscope structure of projecting neurons in the cat's visual
      claustrum.

PMID- 9243911
TI  - Types of renal arteries in aspect of the reconstruction operation of the
      abdominal aorta.

PMID- 9243912
TI  - Microsurgical anatomy of the anterior communicating artery.

PMID- 9243913
TI  - Applied anatomy of the extracerebral part of the arteria centralis longa.

PMID- 9243914
TI  - Morphological features of the patella and its ligament before and after birth.

PMID- 9243915
TI  - Metric features of the human triceps brachii.

PMID- 9243916
TI  - Anthropomorphology of levator scapulae muscle.

PMID- 9243918
TI  - Subscapular artery as a material for aorto-coronary bypass graft.

PMID- 9243917
TI  - Effect of naklofen, alcohol and naklofen administered simultaneously with alcohol
      on transaminase levels.

PMID- 9243919
TI  - To make uniform of the cervical lymph nodes for surgery of the esophageal cancer.

PMID- 9243920
TI  - The histological changes of the pancreatic tissue during the course of acute
      experimental pancreatitis treated with Fibrolan.

PMID- 9243921
TI  - Changes of amylase levels in the acute experimental pancreatitis treated with
      Fibrolan.

PMID- 9243922
TI  - Variability of shape and ultrastructure of supporting cell nuclei (Sertoli cells)
      in the European bison.

PMID- 9243923
TI  - Microsurgical anatomy of the final division of the basilar artery.

PMID- 9243924
TI  - Branching axon from pons and raphe nuclei project to cerebellar paramedian lobule
      as studied with the double fluorescent retrograde tracing technique.

PMID- 9243925
TI  - Age related changes in the density of blood vessels in the human sciatic nerve.

PMID- 9243926
TI  - The intratesticular lymphatic network in men, bulls and rams.

PMID- 9243927
TI  - Ultrastructure of the glial cells after spinal cord compression in rabbits.

PMID- 9243928
TI  - The orifice of superior thyroid vein to the internal jugular vein in human
      fetuses.

PMID- 9243929
TI  - Morphological changes of the accessory male sexual glands of rats treated with
      estrogens during neonatal period.

PMID- 9243930
TI  - Anatomy of the anterior choroidal artery--clinically orientated study.

PMID- 9243931
TI  - An implication to the role of testicular serotonergic innervation. An in vitro
      study on serotonin effects in the control of Leydig cell secretory function.

PMID- 9243932
TI  - A promising rat model of Alzheimer's disease-like neuropathology.

PMID- 9243933
TI  - Increase of cerebral blood flow in rats after human b-amyloid peptide infusion.

PMID- 9243934
TI  - Early development of the human sphincter urethrae muscle.

PMID- 9243935
TI  - Postnatal development of nuclei mamillare in guinea pig (Cavia porcellus L.).

PMID- 9243936
TI  - Histochemical detection of dystrophin in Purkinje neurons of mouse cerebellum.

PMID- 9243937
TI  - Fractal analysis of adults cerebellum surface NMR observations.

PMID- 9243938
TI  - Fractal description of cerebellum surface during fetal period.

PMID- 9243939
TI  - Calcium binding proteins in the development of central nucleus of amygdaloid body
      -a morphometric and immunohistochemical study.

PMID- 9243940
TI  - Application of the coupled harmonic oscillators model to the description of beta
      cells of the pancreatic langerhans islets.

PMID- 9243941
TI  - Brain stem implantable electrodes in management of total deafness after removal
      of acoustic neuroma--a review of operative approaches.

PMID- 9243942
TI  - Differentiation of neurons populations based on fractal dimension.

PMID- 9243943
TI  - Morphology and topography of dormouse (Muscardinus avellanarius L.) and gopher
      (Spermophilus suslicus Guld.) olivary nucleus. The comparative studies.

PMID- 9243944
TI  - The development of the atrioventricular valves in staged human embryos.

PMID- 9243945
TI  - Lymphatic outflow of the cerebrospinal fluid in rats.

PMID- 9243946
TI  - The existence of superficial veins on the mediastinal surface of the superior and
      posterior segments of the left upper pulmonary lobe.

PMID- 9243947
TI  - The variety of arising the left upper pulmonary vein in man.

PMID- 9243948
TI  - The ways of division the basal portion (pars basalis) of the left pulmonary
      artery.

PMID- 9243949
TI  - Morphometric features of recti muscles of the eye and their muscle spindles in
      human fetuses.

PMID- 9243950
TI  - The effect of environmental xenobiotics on histoenzymatic characteristics of
      human placentae collected in Silesian copper mining territory.

PMID- 9243951
TI  - The arterial supply of the thoracic part of human fetal spinal cord SEM of
      vascular corrosion casts.

PMID- 9243952
TI  - Morphological changes in endothelial cells of uterine artery of cycling and
      ovariectomized-estradiol treated ewes.

PMID- 9243953
TI  - Morphometrical, ultrastructural study of satellite cells derived from musculus
      extensor digitorum longus in rats subjected to hypokinesia (7, 14 and 21 days).

PMID- 9243954
TI  - Access to health care. Part 2: Working-age adults.
AB  - OBJECTIVES: This report presents data on access to health care for U.S. working
      age adults, 18-64 years old. Access indicators are examined by selected
      sociodemographic characteristics including sex, age, race and/or ethnicity, place
      of residence, employment status, income, health status, and health insurance
      status. METHODS: Data are from the 1993 Access to Care and 1993 Health Insurance
      Surveys of the National Health Interview Survey (NHIS), a continuing household
      survey of the civilian noninstitutionalized population of the United States. The
      sample contained 61,287 persons in 24,071 households. RESULTS: In 1993,
      approximately 3 out of 4 working-age adults had a regular source of medical care.
      Nine out of 10 adults with health insurance had a regular source of care compared
      with 6 out of 10 adults without health insurance. For adults with a regular
      source of care, 86 percent received care in a private doctor's office, 9 percent
      in a clinic, and 2 percent in a hospital emergency room. The two main reasons
      given for not having a regular source of care were "do not need a doctor" (49
      percent), and "no insurance can't afford it" (22 percent). Persons in the highest
      income group were more likely to report no need for a doctor (59 percent) than
      persons in the lowest income group (35 percent). About 40 percent of uninsured
      persons and 16 percent of insured persons reported an unmet medical need.
      CONCLUSIONS: Health insurance plays a key role in the access to medical care
      services. Persons who are uninsured or have low incomes are at the greatest risk
      of having unmet medical needs.

PMID- 9243955
TI  - Evaluating the role of physical, operant, cognitive, and affective factors in the
      pain behaviors of chronic pain patients.
AB  - Behavioral manifestations of pain, distress, and suffering have been
      characterized as pain behaviors. Although acquisition and maintenance of pain
      behaviors have been considered to occur through reinforcement contingencies,
      empirical evidence suggests that pain behavior is better understood as a
      multidimensional entity. The present study was designed to evaluate the
      contributions of physical, operant, cognitive, and affective factors to
      individual differences in pain behaviors. A total of 63 chronic pain patients
      diagnosed with the disorder fibromyalgia underwent medical, physical, and
      psychological evaluations. Hierarchical regression analyses revealed that the
      physical, cognitive, and affective factors, but not operant factors, were
      significantly related to observed pain behaviors. The set of all factors
      accounted for 53% of the variance in observed pain behavior. The results in this
      study suggest that pain behaviors should be conceptualized as behavioral
      manifestation of pain based on a complex interaction of various psychological and
      physical factors.

PMID- 9243956
TI  - Evaluating AIDS-related social skills in Anglo and Latino adolescents. Focus on
      assessment.
AB  - The purpose of this study was to examine the assessment of AIDS-related social
      skills (measured by role play) in Anglo and Latino adolescents (N = 383) and to
      explore ethnic and gender differences on these skills. Eight skills were assessed
      on five measures evaluating molar, molecular, verbal, and nonverbal dimensions of
      behavior. Interrelationships between skills and measurement dimensions were
      examined using factor analysis. Results revealed that Anxiety and Nonverbal
      Behavior each loaded across different skills on individual respective factors,
      whereas verbal content and assertiveness measures loaded by skill on separate
      factors. Differences in skill emerged between female and male, and Latino and
      Anglo youth. Preliminary social validity data were collected for the skills
      assessed. Social validity results were skill specific, with judges validating
      certain skills and certain measurement dimensions more than others. Implications
      for future assessment and intervention research of AIDS-related social skills are
      discussed.

PMID- 9243957
TI  - Scripted sequences of teacher interaction. A versatile, low-impact procedure for
      increasing appropriate behavior in a nursery school.
AB  - Sequences of managerial statements delivered by a teacher during supervised
      playtime were identified, and a scripting procedure was used to modify these
      sequences while retaining the overall structure of teacher-student interactions.
      Five preschool-age children participated in the study. Following an initial
      assessment phase, the alternative sequence of scripted interactions was
      implemented first by an experimenter using an ABAB reversal design and then by
      the classroom teacher. The scripted interaction sequence was effective in
      increasing levels of appropriate play behavior in all five children, and these
      levels were maintained when control of the procedure was transferred to the
      teacher. Moreover, the teacher quickly learned to implement the procedure, did so
      with a high degree of integrity, and judged it to be moderately acceptable. The
      value of scripted interactions as an effective yet flexible management strategy
      that can be used in teacher training is discussed.

PMID- 9243958
TI  - A review of cognitive behavioral and pharmacological treatment of body dysmorphic
      disorder.
AB  - Body dysmorphic disorder (BDD) first appeared in the diagnostic nomenclature in
      1987 with the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition
      Revised (DSM-III-R) (APA, 1987). Currently in DSM-IV (APA, 1994), the criterion
      of impairment in functioning was added to the already existing criteria of
      preoccupation with an imagined defect in appearance not accounted for by another
      mental disorder. The body parts most often perceived as defective are the nose,
      hair, and complexion. Behavioral and pharmacological studies consist primarily of
      case reports. Systematic desensitization, exposure and response prevention, and
      cognitive therapy are promising approaches that need further investigation.
      Pharmacological agents noted to be beneficial are the selective serotonin
      reuptake inhibitors. Controlled studies in this area are also needed.

PMID- 9243959
TI  - Perceived effective problem solvers' attributions concerning success and failure
      of a simulated real-life problem.
AB  - The present study examined the effect of perceived problem-solving ability (self
      identified effective and ineffective) operationalized by Heppner and Petersen's
      Problem Solving Inventory (PSI) and random feedback (success vs. failure) on
      participants' attributions. A total of 30 female and 30 male teacher trainees who
      had scored in the top and bottom distribution of the PSI dealt with three
      unexpected classroom disruptions during a lecture presentation. After their
      presentation, they received randomized feedback concerning their performance
      during disruptions. Following feedback, they completed Baumgardner's Attribution
      Questionnaire (AQ). Results indicated a significant PSI x Feedback interaction
      for ability and effort but not for task difficulty and luck. Perceived
      efficacious problem solvers' internal attributions depended on whether they
      received success or failure feedback. Similar to the self-enhancing tendency
      reported in the literature, this group attributed success versus failure more to
      ability and effort. The perceived ineffective problem solvers' attributions did
      not differ based on the feedback they received. Results are discussed in terms of
      prior research and theory.

PMID- 9243960
TI  - Behavioral expressions of intolerance of uncertainty in worry. Experimental
      findings.
AB  - Intolerance of uncertainty has been related to increased worry in recent
      conceptual models of Generalized Anxiety Disorder (GAD). The present study
      examines the relationship between a measure of intolerance of uncertainty, the
      Intolerance of Uncertainty scale (IU), and behaviors associated with GAD, such as
      slowness of execution and amount of evidence required before decision making. A
      total of 49 individuals participated in the study. Three experimental tasks
      varying in level of ambiguity and difficulty were used. The analyses show a
      positive correlation between scores on the IU and number of cues required before
      responding in a moderately ambiguous inference task. However, scores on the IU
      were not significantly related to responses in an unambiguous task (regardless of
      the level of difficulty) or in a highly ambiguous task. The results suggest that
      high worriers have a lower threshold of tolerance of uncertainty for intermediate
      levels of ambiguity. The results are discussed in terms of theoretical models of
      GAD.

PMID- 9243961
TI  - Dissociations in infant memory: rethinking the development of implicit and
      explicit memory.
AB  - Extending the Jacksonian principle of the hierarchical development and
      dissolution of function to the development and dissolution of memory, researchers
      have concluded that implicit (procedural) memory is a primitive system,
      functional shortly after birth, that processes information automatically, whereas
      explicit (declarative) memory matures late in the 1st year and mediates the
      conscious recollection of a prior event. Support for a developmental hierarchy
      has only been inferred from the memory performance of adults with amnesia on
      priming and recognition-recall tests in response to manipulations of different
      independent variables. This article reviews evidence that very young infants
      exhibit memory dissociations like those exhibited by adults with normal memory on
      analogous memory tests in response to manipulations of the same independent
      variables. These data demonstrate that implicit and explicit memory follow the
      same developmental timetable and challenge the utility of conscious recollection
      as the defining characteristic of explicit memory.

PMID- 9243962
TI  - The emergence and early development of autobiographical memory.
AB  - The authors provide a new framework that integrates autobiographical memory with
      other early achievements (e.g., gesturing, language, concept formation). In this
      theory, the emergence and early development of autobiographical memory does not
      require the invocation of specialized neurological or multiple memory mechanisms
      but rather arises as a natural consequence of developments in related domains
      including in the "software" that drives general memory functioning. In
      particular, autobiographical memory emerges contemporaneously with the cognitive
      self, a knowledge structure whose features serve to organize memories of
      experiences that happened to "me." Because this cognitive self emerges in the 2nd
      year of life, the lower limit for early autobiographical memories is set at about
      2 years, with subsequent accumulation of memories linked to improvements in
      children's ability to maintain information in storage.

PMID- 9243963
TI  - Mr. Chips: an ideal-observer model of reading.
AB  - The integration of visual, lexical, and oculomotor information is a critical part
      of reading. Mr. Chips is an ideal-observer model that combines these sources of
      information optimally to read simple texts in the minimum number of saccades. In
      the model, the concept of the visual span (the number of letters that can be
      identified in a single fixation) plays a key, unifying role. The behavior of the
      model provides a computational framework for reexamining the literature on human
      reading saccades. Emergent properties of the model, such as regressive saccades
      and an optimal-viewing position, suggest new interpretations of human behavior.
      Because Mr. Chip's "retina" can have any (one-dimensional) arrangement of high
      resolution regions and scotomas, the model can simulate common visual disorders.
      Surprising saccade strategies are linked to the pattern of scotomas. For example,
      Mr. Chips sometimes plans a saccade that places a decisive letter in a scotoma.
      This article provides the first quantitative model of the effects of scotomas on
      reading.

PMID- 9243964
TI  - Handedness and speech: a critical reappraisal of the role of genetic and
      environmental factors in the cerebral lateralization of function.
AB  - Functional predominance of the left cerebral hemisphere with regard to both
      handedness and speech has usually been assumed to be due to some underlying
      neural specialization that is predetermined and inborn. However, data from left
      handed individuals and animal experiments, together with a consideration of the
      effects of natural selection on brain and behaviour during hominid evolution, are
      incompatible with such an explanation. A critical reexamination of the relevant
      nonhuman and human evidence suggests that although the development of a cerebral
      lateralization for speech and handedness is dependent on both genetic and
      environmental factors, the specific role of inborn and postnatal influences is
      very different. This has significant implications for a fundamental revision of
      current theory and research orientation.

PMID- 9243965
TI  - Cortical dynamics of lateral inhibition: metacontrast masking.
AB  - The dynamic properties of a neural network model of visual perception, called the
      boundary contour system, explain characteristics of metacontrast visual masking.
      Computer simulations of the model, with a single set of parameters, demonstrate
      that it accounts for 9 key properties of metacontrast masking: Metacontrast
      masking is strongest at positive stimulus onset asynchronies (SOAs); decreasing
      target luminance changes the shape of the masking curve; increasing target
      duration weakens masking; masking effects weaken with spatial separation;
      increasing mask duration leads to stronger masking at shorter SOAs; masking
      strength depends on the amount and distribution of contour in the mask; a second
      mask can disinhibit the masking of the target; such disinhibition depends on the
      SOA of the 2 masks; and such disinhibition depends on the spatial separation of
      the 2 masks. No other theory provides a unified explanation of these data sets.
      Additionally, the model suggests a new analysis of data related to the SOA law
      and makes several testable predictions.

PMID- 9243966
TI  - Cortical dynamics of three-dimensional figure-ground perception of two
      dimensional pictures.
AB  - This article develops the FACADE theory of 3-dimensional (3-D) vision and figure
      ground separation to explain data concerning how 2-dimensional pictures give rise
      to 3-D percepts of occluding and occluded objects. The model describes how
      geometrical and contrastive properties of a picture can either cooperate or
      compete when forming the boundaries and surface representation that subserve
      conscious percepts. Spatially long-range cooperation and spatially short-range
      competition work together to separate the boundaries of occluding figures from
      their occluded neighbors. This boundary ownership process is sensitive to image T
      junctions at which occluded figures contact occluding figures. These boundaries
      control the filling-in of color within multiple depth-sensitive surface
      representations. Feedback between surface and boundary representations
      strengthens consistent boundaries while inhibiting inconsistent ones. Both the
      boundary and the surface representations of occluded objects may be amodally
      completed, while the surface representations of unoccluded objects become visible
      through modal completion. Functional roles for conscious modal and amodal
      representations in object recognition, spatial attention, and reaching behaviors
      are discussed. Model interactions are interpreted in terms of visual, temporal,
      and parietal cortices.

PMID- 9243967
TI  - The Italian contribution to facial plastic surgery: a historical reappraisal.

PMID- 9243968
TI  - Magnetic resonance imaging in primary and secondary septorhinoplasty.
AB  - The authors emphasize the importance of MRI as a means to functionally evaluate
      patients in primary (PR) and secondary (SR) rhinoseptoplasty. Forty-eight
      subjects were appraised who underwent various types of corrective nose surgery:
      31 PR, 12 SR, 4 introgenic perforations, and 1 dermoid cyst of the nasal dorsum.
      MRI allows the nasal structures at the level of the valve to be visualized, as
      well as the medial and lateral walls of the nasal fossa in all of its components.
      MRI studies improve pre-surgical evaluation (alar cartilages, iaterdomal
      distance, and valvular configuration), and the exam of structures and anomalies
      which are hard to evaluate by the rhinoscopy (turbino-septal-synchias,
      perforations, losses of bone-cartilaginous substance). Moreover, through MRI the
      nasal respiratory surface (NRS) is determined and used by the authors to quantify
      the improvement of the postsurgical nasal respiratory function. All of these
      points gain importance during the planning of primary, secondary, and/or
      corrective surgery.

PMID- 9243969
TI  - Tailored nasal surgery for normalization of nasal resistance.
AB  - The nose acts as a physiologic airway resistor, accounting for around 50% of
      total airway resistance. Adequate nasal resistance is essential not only for
      correct functioning of the nose but to ensure normal pulmonary physiology.
      Pathological nasal resistance is determined by alterations in the shape and
      volume of the nasal cavities that singly or in association disrupt nasal
      aerodynamics, a condition that will present mainly in the form of obstructive
      disorders. The authors advise against considering nasal cavity surgery simply as
      surgery of the nasal septum. Nasal surgery should be addressed to normalizing the
      geometry of the nasal cavities in order to restore physiologic nasal resistance.
      Surgical procedures may be classified as follows: (1) surgery of the medial wall;
      (2) surgery of the lateral wall; and (3) surgery of the valve area. Septal
      surgery is systematically performed by the authors using the maxilla-premaxilla
      approach (MPA). Functional correction of the septum combines mobilization and/or
      removal of any deranged portion of the bony and/or cartilaginous septum, followed
      by reconstruction of the septum support, preferably using autogenous septal
      grafts. When reconstructing the medial wall, great care must be taken with the
      most important portion of the septum, i.e., the dorso-caudal margin and the
      cartilaginous elements. We have called this procedure Functional
      Osteocartilaginous Reconstruction of the Nasal Septum (FORNS). Obstructive
      swelling of the turbinates is one of the most common causes of nasal obstruction
      as it alters the shape and reduces the volume of the nasal cavities causing an
      exponential increase in nasal resistance. With regard to surgery of the lateral
      wall, the authors firmly believe that mutilating procedures like total inferior
      turbinectomy can in no way be considered functional surgery of the turbinates. On
      the contrary, aim of lateral wall functional surgery is not simply to widen the
      airway, but rather to restore normal aerodynamic contours to the lateral wall in
      order to prevent turbulence, a phenomenon which will cause increased nasal
      resistance. To do this, the authors make systematic use of Conservative
      Submucosal Turbinoplasty (CST). The procedure is designed especially to treat the
      submucosa since this is the main focus of anatomo-pathological alterations. Nasal
      valve surgery is one of the most high-risk surgical procedures since scarring,
      stiffening, or loss of structural support may cause severe and even irreversible
      damage. Any surgery of the valve area should therefore carry minimum risk of
      respiratory complications and aesthetic defects. In the light of these
      principles, the authors propose a valve area correction technique carried out
      exclusively through the hemitransfixion incision. This approach affords wide
      access to the whole valve area, allowing the rhino-surgeon to perform a range of
      corrections on the anatomic sub-units constituting the nasal valve complex. This
      same approach can be used to place various grafts. The authors propose a
      "tailored surgery to normalize the nasal resistances," i.e., a systematic surgery
      to reshape the volume of the various segments of the nasal chambers by
      repositioning as close to normalcy as possible the disrupted skeletal framework
      and recontouring streamlined nasal walls.

PMID- 9243971
TI  - Surgery of the nasal tip: a personal approach.

PMID- 9243970
TI  - Interrupted and continuous strip technique for tip surgery during traditional
      rhinoplasty.
AB  - The authors report their experience in corrective surgery of the tip during
      traditional closed rhinoplasty. After a critical revision of the proposed
      techniques by other authors, the advantages of the "Doberman's ears" and
      "Butterfly" are given. The choice of the corrective techniques of the tip next to
      Tardy's algorithm can use a "sequential criterium" after having used a delivery
      approach. During rhinoplasty it is possible to perform a system of "progression"
      from one method to another maintaining or interrupting the cartilaginous arch and
      having as a goal the increasing or the decreasing of the tip.

PMID- 9243972
TI  - Secondary unilateral cleft lip nose: the external approach.
AB  - No single procedure developed until now has given satisfactory results to provide
      an ideal surgical method for cleft lip nasal deformity correction. This paper
      emphasizes the concept that nasal surgery is the end result on an overall
      treatment program for secondary cleft lip. The first step is correcting skeletal
      deformities. The second step of modifying the overlying nasal pyramid can only be
      performed when the alar base and the floor of the nose are at the same level
      through orthodontic alignment of the maxillary segments and bone grafting. Prior
      to deciding on the type of strategy, it is essential to carefully analyze the
      severity of the deformity, the patency of the airways, the nasal lining, and the
      nasal tip projection. An external approach, using the marginal-transcolumellar
      incision, provides excellent visualization essential for the accuracy of the
      correction to be carried out. The technique presented here includes modification
      of the following points as a single stage operation: septal surgery, suturing the
      medial crura together, suspension of the alar cartilage to the periosteum of the
      nasal bone, alar base repositioning, orbicularis muscle suturing, and increasing
      tip projection.

PMID- 9243973
TI  - The future of face lifts: a comparison between traditional surgery and advanced
      techniques.

PMID- 9243974
TI  - Foreword complication or mistake?

PMID- 9243975
TI  - Complications of septal surgery.
AB  - Complications associated with submucous septal resection or septoplasty may
      originate in incorrect indication and diagnosis because of wrong or incomplete
      analysis and interpretation of the anatomical structures of the nose and nasal
      function tests. Complications can arise from technical failures during the
      procedures of septal surgery from the incision to the reconstruction of the
      septum. Early and late complications can be caused by infections in the
      postoperative period involving only the midfacial region or the whole body.
      Postoperative and late complications may also arise from damage to the septal
      soft and hard tissues. Although septal surgery complications may interfere with
      nasal function, cosmesis, and general health, prospective studies with subjective
      and objective data are extremely rare.

PMID- 9243976
TI  - Complications of pyramid surgery.

PMID- 9243977
TI  - Complications and sequelae of nasal base and tip surgery.

PMID- 9243978
TI  - Complications following implantation or transplantation in rhinoplasty.

PMID- 9243979
TI  - Skin and soft tissue complications.

PMID- 9243980
TI  - Systemic and other complications.

PMID- 9243981
TI  - Psychological complications of septo-rhinoplasty.

PMID- 9243982
TI  - Micrographic surgery of malignant skin tumors: a comparison of the frozen
      technique with paraffin sectioning.

PMID- 9243983
TI  - Subcutaneously pedicled island flaps.
AB  - Subcutaneously pedicled island flaps (SPIF) are very mobile local flaps bringing
      into the surgical defect skin of similar texture and color to that of the
      recipient site. SPIF flaps are eminently simple to create: an island of skin is
      incised until the fatty tissue is visualized and the flap connections to
      surrounding tissue are carefully disconnected without damaging the nutrient
      vessels. The viability of such flaps is excellent. If appropriately performed,
      side effects such as pincushioning are rare.

PMID- 9243984
TI  - The reversed dermal graft: surgical procedure and clinical applications.
AB  - The reversed dermal graft has been employed in reconstructive plastic surgery for
      almost 80 years. It is recommended that the dermatologic surgeon use this graft
      technique whenever a case calls for the combined advantages of the split
      thickness skin graft for poorly vascularized areas and the axial pedicle flap
      appropriate to areas subject to marked mechanical strain. We present cases in
      which defects on the scalp, sole, palm, and great toe have been covered by
      reversed dermal graft and split-thickness skin graft in a single operation with
      excellent results. Our modification of the technique has proved that simultaneous
      grafting with reversed dermis and split-thickness skin graft produces
      satisfactory results, reduces postoperative care by 2 weeks, and obviates
      repeated anesthesia.

PMID- 9243985
TI  - Treatment of skin tumors of the inner canthal region--reconstructing the medial
      canthal area: a dilemma between doing too much and an aesthetic outcome.

PMID- 9243986
TI  - Aesthetic reconstruction of nasal defects using forehead flaps.

PMID- 9243987
TI  - Improving the aesthetic aspect of soft tissue defects on the face using
      autologous fat transplantation.
AB  - The correction of contour defects presents a surgical challenge. Many attempts
      have been made during the past decades to correct skin defects with biologic,
      artificial, or autologous implants. Unfortunately most biologic materials are
      resorbed within a few months and the artificial ones are reported to cause
      complications. In recent years the transplantation of autologous fat, after
      liposuction with the syringe method, has become an established method. The
      survival of the transplanted fat tissue is still a controversial subject. Since
      1987, we have been performing microlipotransplantation of autologous fat to
      correct contour defects, mainly of the face. We have treated a total of 176
      patients with different tissue defects. With follow-up as long as 8 years, the
      best results were with scars and atrophies. For augmentation of soft tissue
      defects with dermal and subdermal components, the autologous transplantation of
      lipoaspirated fat tissue seems to be the treatment of choice.

PMID- 9243988
TI  - Regional approaches to the reconstruction of the lip region.
AB  - Surgical operations on the lips are characteristically required when dealing with
      epithelial tumors in dermatosurgery. Aside from precancerous stages, the
      definitive removal of basal cell carcinomas and squamous cell carcinomas is most
      common. The immediate reconstruction of lip defects proves successful, utilizing
      the histologic examination of the cut edge by cryotechnique. All operative
      techniques that reconstruct the circular musculature of the musculus orbicularis
      oris in its natural uniformity are appropriate. Of the large variety of
      reconstructive procedures, this article discusses those techniques that are used
      routinely.

PMID- 9243989
TI  - Combining tumorradicality with functionality consideration for a maximum of
      aesthetic repair after micrographic surgery of the ear.

PMID- 9243990
TI  - Anatomic considerations in rhytidectomy.

PMID- 9243991
TI  - Effective management of the superficial musculoaponeurotic system as an
      alternative to composite rhytidectomy.

PMID- 9243992
TI  - Deep-plane/composite rhytidectomy.

PMID- 9243993
TI  - Management of aging neck.

PMID- 9243994
TI  - The male facelift: considerations and techniques.
AB  - Facelift in the male patient presents unique challenges with respect to
      maintenance of normal hairline and management of bearded skin. With careful
      psychological preparation, surgical planning, and attention to detail, these male
      characteristics can be retained with a good rejuvenative result. The combination
      of a deep-plane rhytidectomy technique with modified incisions and endoscopic
      brow intervention has provided the authors with consistent surgical results.
      Complications have been minimal, with no significant hematomas, skin loss, or
      nerve injuries to date.

PMID- 9243995
TI  - Cosmetic surgery of the lips.
AB  - Lips are the central feature in the lower third of the face. When they are full
      and well defined, they impart a sense of youth, health, and attractiveness to the
      bearer. Thin, flat lips, on the other hand, imply fragility and senility. The
      characteristics of the lips responsible for these qualities are the shape of
      Cupid's bow, the relative length of the upper lip, and the projection or bulk of
      the lips. Esthetic guidelines are presented for each of these characteristics,
      which when understood help the surgeon formulate an operative plan. Lip
      augmentation techniques using autogenous and alloplastic materials are presented.
      For patients with a long upper lip, vermilion advancement and nasal base
      resection are discussed in detail. With a look to the future, a discussion of
      preliminary experience with carbon dioxide laser lip advancement concludes the
      article.

PMID- 9243996
TI  - Chin augmentation/genioplasty: chin deformities in the aging patient.

PMID- 9243997
TI  - Facial skeletal surgery in the aging face.
AB  - Modifications of the facial skeleton with alloplastic augmentation, on-lay
      grafts, or repositioning of bony fragments by osteotomy are extremely useful
      adjuncts in rejuvenation of the aging face. Minor disharmonies with normal dental
      occlusion can usually be best achieved with on-lay grafts or alloplastic
      augmentation. More extensive deformities require osteotomy and repositioning of
      bony parts. Reductions in height and anterior projection must be performed with
      caution because soft tissues do not shrink as readily in patients over 30 years
      of age.

PMID- 9243998
TI  - The use of fillers in the aging patient.

PMID- 9243999
TI  - Endoscopic techniques in facial rejuvenation surgery.
AB  - The endoscopic approach to rejuvenation surgery of the forehead is standing the
      test of time. We feel that aesthetic results obtained from this procedure are
      equal to or better than results associated with the conventions coronal lift,
      while remarkably reducing recovery time and incision-related morbidity (Figs.
      9,10).

PMID- 9244000
TI  - Basic techniques in microvascular anastomosis.

PMID- 9244001
TI  - Clinical vessel anastomosis in head and neck free tissue transfer.

PMID- 9244002
TI  - Perioperative patient management of free flaps.

PMID- 9244003
TI  - Flap monitoring.

PMID- 9244004
TI  - Failing flap.

PMID- 9244005
TI  - Radial forearm free flap for head and neck reconstruction.

PMID- 9244006
TI  - Iliac crest free flap.

PMID- 9244007
TI  - Overview of the rectus abdominis myocutaneous flap in head and neck
      reconstruction.
AB  - The functional and aesthetic consequences of ablative head and neck oncologic
      surgery pose a significant challenge to the reconstructive surgeon. With the
      advent of microvascular free tissue transfer the reconstructive capabilities of
      the surgeon have been greatly expanded. The rectus abdominis musculocutaneous
      free flap has assumed an important role in contemporary head and neck
      reconstruction because of its ease of dissection, length and size of the vascular
      pedicle, convenience of harvest in the supine position, reliability and
      versatility, and low donor site morbidity.

PMID- 9244008
TI  - Fibula free flap.

PMID- 9244009
TI  - Scapular and parascapular free flaps.

PMID- 9244010
TI  - Latissimus dorsi microvascular flap.

PMID- 9244011
TI  - Free jejunal transfer.

PMID- 9244012
TI  - Lateral thigh free flap.

PMID- 9244013
TI  - Other flaps for head and neck use: temporoparietal fascial free flap, lateral arm
      free flap, omental free flap.
AB  - Advances in microvascular surgery have led to the development of new donor sites
      for head and neck reconstruction. The superficial temporoparietal, lateral arm,
      and omental free flaps represent three flaps with primarily soft tissue uses.
      Their reliable blood supply and pliability make them well suited for a variety of
      head and neck defects. The superficial temporoparietal and lateral arm free flaps
      may be used as osteocutaneous flaps, but more rarely is this the case. Minimal
      donor site morbidity is an advantage with the superficial temporoparietal and
      lateral arm flaps. The morbidity of a laparotomy must be weighed against the
      advantage gained by employing the omental free flap in cases of soft tissue
      reconstruction.

PMID- 9244014
TI  - Uncommon and experimental microvascular free flaps in head and neck
      reconstruction.

PMID- 9244015
TI  - Free flap options for common head and neck defects.
AB  - A summary of first, second, and uncommon or new free flap options is shown in
      Table 1. It serves as a general guideline for head and neck defects.

PMID- 9244016
TI  - Airway management in the recovery room.

PMID- 9244017
TI  - Gastric tonometry and prediction of outcome in the critically ill. Arterial to
      intramucosal pH gradient and carbon dioxide gradient.
AB  - Splanchnic ischaemia is thought to be of central importance in the development of
      multi-organ failure and hence death in critically ill patients. It has been
      suggested that the arterial to gastric intramucosal pH gradient and the
      difference in partial pressure of carbon dioxide between gastric mucosa and
      arterial blood are more sensitive markers of splanchnic ischaemia than gastric
      intramucosal pH itself and thus should be predictors of mortality in the
      critically ill. We studied 62 critically ill patients within 6 h of admission to
      the intensive care unit and found no significant difference at 0, 12 or 24 h
      after admission to the study in either the arterial to gastric intramucosal pH
      gradient or the difference in partial pressure of carbon dioxide between gastric
      mucosa and arterial blood between survivors and nonsurvivors. We conclude that in
      contrast to gastric intramucosal pH neither the arterial to gastric intramucosal
      pH gradient nor the difference in partial pressure of carbon dioxide between
      gastric mucosa and arterial blood distinguish survivors from nonsurvivors.

PMID- 9244018
TI  - The peri-operative use of the oesophageal Doppler monitor in patients undergoing
      coronary artery revascularisation. A comparison with the continuous cardiac
      output monitor.
AB  - This study was carried out to evaluate the ease of use and reliability of cardiac
      output estimations performed by an oesophageal Doppler monitor and to compare its
      use with that of a continuous cardiac output pulmonary flotation catheter.
      Measurements were made during and after surgery in 16 patients scheduled to
      undergo coronary revascularisation. Both devices suffered significant intra
      operative problems which led us to question their suitability as operating
      theatre monitors. After surgery the continuous cardiac output monitor provided
      stable results while the oesophageal Doppler monitor required the continuous
      presence of an experienced anaesthetist to ensure comparable cardiac output
      estimations.

PMID- 9244019
TI  - A noninvasive method for evaluating the effect of thoracotomy on shunt and
      ventilation perfusion inequality.
AB  - A new noninvasive method was used to evaluate gas exchange in 12 patients
      undergoing thoracotomy for a variety of surgical procedures. A plot of inspired
      oxygen partial pressure versus oxygen saturation was analysed to calculate the
      independent contribution of shunt and intermediate ventilation/perfusion ratio
      which occurs during general anaesthesia for thoracotomy. A model based on the
      inspired to arterial oxygen difference involving the shunt equation was used to
      show how the relationship between inspired oxygen partial pressure and oxygen
      saturation could be used to derive two parameters of oxygen exchange, the virtual
      shunt and an index of low ventilation/perfusion ratio. In all cases, there was a
      very good fit of the data to the model. Thoracotomy caused a mean increase in
      shunt from 13.8% to 20.8% and a worsening ventilation/perfusion ratio from 0.5 to
      0.2, the magnitude of which depended on the underlying pathology. In two
      patients, the ventilation/perfusion ratio decreased to less than 0.1. The method
      enables the prediction of oxygen saturation at different inspired oxygen partial
      pressures and allows the two components of gas exchange to be isolated using
      simple routine measurements of inspired oxygen and pulse oximetry.

PMID- 9244020
TI  - The loss of sevoflurane from a closed breathing system.
AB  - When volatile anaesthetics are used in a closed breathing system it is usually
      assumed that inflow of anaesthetic to the system matches uptake by the patient.
      Early laboratory reports on the interactions between sevoflurane and soda lime
      cast doubt on that assumption. We have measured the loss of sevoflurane,
      desflurane and isoflurane from a closed breathing system and found no differences
      of consequences.

PMID- 9244021
TI  - Are coagulation studies on blood sampled from arterial lines valid?
AB  - Coagulation tests were performed on two venous blood samples and two blood
      samples from arterial lines taken from 79 patients on an intensive care unit. For
      the first arterial sample the discard volume was 4.5 ml and for the second
      arterial sample the discard volume was 16 ml. From each pair of venous samples a
      mean venous coagulation value was calculated. There were statistically
      significant differences between arterial and venous results and between the two
      arterial samples for activated partial thromboplastin time and thrombin time
      assays but not for prothrombin time, reptilase time and fibrinogen assays.
      However, these differences were sufficiently small to be of little clinical
      significance. The bias for the difference in activated partial thromboplastin
      time values between the first arterial sample and the venous sample was +1.24 s
      (limits of agreement: -4.39 to +6.87 s) and between the second arterial sample
      and the venous sample the bias was +0.89 s (limits of agreement: -3.25 to +5.03
      s). Only 3.8% of first arterial samples and 1.3% of second arterial samples
      produced activated partial thromboplastin time values that were more than 10%
      longer than the corresponding venous values. No heparin was detectable in these
      arterial samples using a heparin assay (< 0.02 iu.ml-1). The differences between
      arterial and venous activated partial thromboplastin times were slightly but not
      significantly greater in subgroups of patients with moderately or severely
      deranged coagulation compared with a group with normal coagulation. We conclude
      that samples from arterial lines provide valid activated partial thromboplastin
      time results using a discard volume of either 4.5 ml or 16 ml.

PMID- 9244022
TI  - End-tidal carbon dioxide measurement and breathing system filters.
AB  - Breathing system filters are recommended for use during general anaesthesia.
      Manufacturers of gas sampling equipment recommend that gas is sampled from the
      'machine side' of these filters, thereby avoiding contamination of the sampling
      line and waterlogging in the case of heat and moisture exchangers. The aim of
      this study was to investigate differences between the measured end-tidal carbon
      dioxide values at either side of the filter. Fifteen adults were studied during
      mechanical ventilation and 15 during spontaneous ventilation under general
      anaesthesia. End-tidal carbon dioxide values were significantly lower at the
      machine side of the filter in both groups (p = 0.00001). The measurement error
      induced by the inclusion of the breathing system filter was significantly greater
      in the spontaneously breathing group (p = 0.0004).

PMID- 9244023
TI  - Analgesia after day case laparoscopic sterilisation. A comparison of tramadol
      with paracetamol/dextropropoxyphene and paracetamol/codeine combinations.
AB  - In a prospective, double-blind trial we compared the analgesic efficacy of
      tramadol during the first 24 h after day case laparoscopic sterilisation with two
      commonly prescribed combination analgesics. Seventy-five women were allocated
      randomly to receive oral paracetamol 325 mg/dextropropoxyphene hydrochloride 32.5
      mg, tramadol 50 mg or paracetamol 500 mg/codeine phosphate 30 mg as required
      after a standardised anaesthetic technique. There were no significant differences
      in average or worst pain, sleep disturbance, mobility, number of tablets taken,
      satisfaction or preference for stronger analgesia (26.2% of all patients). The
      incidences of nausea and vomiting were comparable between groups. There was a
      trend towards a lower incidence of central nervous system side-effects
      (drowsiness, dizziness, headache) in the paracetamol/codeine group. Tramadol may
      be considered an alternative analgesic for day case surgery although analgesic
      regimens of greater efficacy are required for many patients. The relative
      incidence of side-effects for tramadol and other analgesics requires further
      evaluation.

PMID- 9244024
TI  - The effect of the lateral decubitus position on vagal tone.
AB  - The average person spends about one-third of their time in a recumbent position.
      However, little is known about the effect of recumbent posture on autonomic
      nervous activity. Manoeuvres which can increase vagal tone have been sought both
      in the normal subject and in patients with heart disease. We have studied the
      autonomic effect of various recumbent positions, namely the supine, left lateral
      decubitus and right lateral decubitus positions, in healthy subjects by using
      spectral heart rate variability analysis. Both time- and frequency-domain
      measures were calculated and compared between the three recumbent positions. The
      normalised high-frequency power was used as the index of cardiac vagal activity,
      the normalised low-frequency power as the index of cardiac sympathetic activity
      and the low-frequency power/high-frequency power ratio as the index of
      sympathovagal balance. The normalised high-frequency power is highest in the
      right lateral decubitus position, followed in decreasing order by left lateral
      decubitus and supine positions. The low-frequency power/high-frequency power
      ratio has the reversed trend as compared with that of the normalised high
      frequency power. These results suggest that cardiac vagal activity is greatest
      when the right lateral decubitus position is adopted.

PMID- 9244025
TI  - Acupuncture in the prevention of postoperative nausea and vomiting.
AB  - The efficacy of intra-operative acupuncture at the PC6 point in the prevention of
      postoperative nausea or vomiting was studied. A double-blind randomised
      controlled study of acupuncture versus placebo was performed in 81 patients
      scheduled for day case gynaecological laparoscopic surgery. Failure of treatment
      was defined as the occurrence of nausea or vomiting prior to or within 24 h of
      discharge. The use of acupuncture reduced the incidence of postoperative nausea
      or vomiting in hospital from 65% to 35% compared with placebo and after discharge
      from 69% to 31% compared with placebo.

PMID- 9244026
TI  - Reshaping the Macintosh blade using biomechanical modelling. A prospective
      comparative study in patients.
AB  - It has been demonstrated that during routine use of the Macintosh blade, great
      forces are exerted on the maxillary incisors. The aim of this study was, by using
      biomechanical modelling, to modify a standard Macintosh blade in order to reduce
      these forces. This resulted in a Macintosh blade with a reduced proximal flange.
      Five anaesthetists performed tracheal intubation in 46 patients using the
      modified (n = 24) or the standard blade (n = 22). The mean (SD) maximal forces
      exerted on the maxillary incisors were 12.7 (8.8) N in patients in the modified
      Macintosh group compared to 25.5 (17.8) N in the standard Macintosh group (p =
      0.008). These results demonstrate that reducing the proximal step of the
      Macintosh laryngoscope results in a reduction of the forces exerted on the teeth
      and suggest that laryngoscope blades with a high proximal step might be more
      traumatic than blades in which the proximal step is reduced.

PMID- 9244027
TI  - The Oxyvent. An anaesthetic machine designed to be used in developing countries
      and difficult situations.
AB  - The Oxyvent is an anaesthetic machine designed specifically for use in the
      developing world and difficult situations. It is made up of four components, each
      of which has, in its own right, already proved to be of great value in difficult
      situations. These are the drawover system, the Penlon Manley Multivent
      Ventilator, the DeVilbiss Oxygen Concentrator and the air compressor. The four
      components are mounted on a simple trolley carrying two oxygen cylinders. The
      Oxyvent can be used to provide anaesthesia in the absence of electricity or
      oxygen or both. It is simple, robust and easily serviceable. It is versatile and
      can be used both as an anaesthetic machine in the operating theatre and as a
      ventilator in an intensive care unit.

PMID- 9244028
TI  - Peri-operative use of nonsteroidal anti-inflammatory drugs in children: analgesic
      efficacy and bleeding.
AB  - Nonsteroidal anti-inflammatory drugs are effective in the management of mild to
      moderate postoperative pain in children. They can decrease or even eliminate the
      need for opioid analgesics, thus reducing or eliminating opioid-induced side
      effects. The increasing peri-operative use of nonsteroidal anti-inflammatory
      drugs in children has, however, raised concerns about complications secondary to
      impaired haemostasis. To examine the extent of this unwanted side-effect, this
      paper reviews the published literature on analgesic efficacy and bleeding
      following the peri-operative use of nonsteroidal anti-inflammatory drugs in
      children. The reviewed literature confirms that haemorrhagic events in the
      postoperative period occur, but results remain inconclusive regarding the
      association between peri-operative use of nonsteroidal anti-inflammatory drugs
      and disordered haemostasis. In order to maximise the benefit of nonsteroidal anti
      inflammatory drugs in children, the risks must be recognised and patients,
      clinical indications, the individual drug, timing and route of administration
      must be selected carefully. Nonsteroidal anti-inflammatory drugs appear to play a
      valuable role in the further improvement of postoperative pain management in
      children.

PMID- 9244029
TI  - Spontaneous remission of left bundle branch block during anaesthesia.
AB  - Routine pre-operative evaluation of a 58-year-old man scheduled for repair of an
      inguinal hernia, disclosed a blood pressure of 200/100 mmHg. This decreased to
      150/100 mmHg after a period of rest. An electrocardiogram taken as a result of
      this chance finding showed left bundle branch block. There were no other
      cardiovascular symptoms or signs. Soon after induction of general anaesthesia,
      the conduction defect disappeared. The return to sinus rhythm was sudden and
      sustained and was not related to changes in heart rate or blood pressure. One
      month later, his electrocardiograph remained normal.

PMID- 9244030
TI  - Postdural puncture symptoms in a child.
AB  - An 11-year-old boy suffered an inadvertent dural puncture during placement of an
      epidural catheter for postoperative analgesia. He developed symptoms of mild
      headache only, but severe and protracted orthostatic nausea and dizziness, which
      eventually resolved completely following epidural blood patch. His symptoms were
      atypical and could have been misinterpreted in the context of dural puncture for
      diagnosis, or for administration of intrathecal chemotherapy. The reported
      incidence of headache following dural puncture in children is low. It may be that
      the manifestations are different from those of adults and that the true incidence
      of symptoms related to leakage of cerebrospinal fluid is higher in children than
      currently recognised.

PMID- 9244031
TI  - An unusual presentation in a patient with metachromatic leukodystrophy.
AB  - A 2-year-old child was admitted with bilateral bronchopneumonia. During
      convalescence he sustained sudden respiratory arrest for which he required
      ventilatory support. He had undergone cholecystectomy 1 month prior to the above
      episode. The pathological examination of the gall bladder mass had revealed the
      features of metachromatic leukodystrophy. Gastro-oesophageal reflux, which is
      associated with this neurological disorder, was suspected to be the cause of this
      sudden respiratory arrest and its presence was confirmed by barium swallow
      examination.

PMID- 9244032
TI  - Comparison of ondansetron, metoclopramide and placebo as premedicants to reduce
      nausea and vomiting after major surgery.
AB  - In a randomised, double-blind study, we have compared the incidence of
      postoperative nausea and vomitting in 124 patients undergoing major lower limb
      orthopaedic surgery following oral premedication with temazapam and ondansetron 8
      mg, metoclopramide 10 mg or placebo. They received a standardised epidural and
      general anaesthetic. An epidural mixture containing bupivacaine 0.1% and fentanyl
      10 mg.ml-1 was infused postoperatively. The occurrence of nausea and vomiting was
      assessed every 4 h for 24 h. The incidence of vomiting significantly decreased
      from 55% and 43% in the placebo and metoclopramide groups, respectively, to 26%
      in the ondansetron group (p = 0.03). The incidence of nausea and vomiting in
      patients who had previously suffered was also significantly reduced from 67% and
      68% in the placebo and metoclopramide groups, respectively, to 29% in the
      ondansetron group (p = 0.035). We conclude that oral premedication with
      ondansetron 8 mg was superior to metoclopramide 10 mg and placebo in preventing
      postoperative nausea and vomiting following major orthopaedic surgery in patients
      given epidural opioid analgesia.

PMID- 9244033
TI  - Co-induction and laryngeal mask insertion. A comparison of thiopentone versus
      propofol.
AB  - Conditions for insertion of the laryngeal mask airway were assessed in 70
      unpremedicated patients comparing the co-induction with midazolam-alfentanil
      thiopentone and midazolam-alfentanil-propofol. Following pre-induction doses of
      midazolam 0.04 mg.kg-1 and alfentanil 10 micrograms.kg-1, patients received
      equipotent doses of either thiopentone or propofol. Whilst jaw relaxation and
      ease of laryngeal mask insertion were similar between the two groups, patients
      receiving propofol were less likely to have undesired responses requiring
      additional boluses of induction agent (p < 0.05). We conclude that, using these
      doses, propofol is superior to thiopentone for laryngeal mask airway insertion
      when using a co-induction technique.

PMID- 9244034
TI  - The contribution of extracranial blood oxygenation on near-infrared spectroscopy
      during carotid endarterectomy.

PMID- 9244035
TI  - The contribution of extracranial blood oxygenation on near infrared spectroscopy
      during carotid endarterectomy.

PMID- 9244036
TI  - Leaks from breathing system gas sampling points fitted with Luer connections.

PMID- 9244037
TI  - Deaths on general wards following discharge from the intensive care unit.

PMID- 9244038
TI  - Continuous gastric tonometry as a monitor of intestinal perfusion.

PMID- 9244039
TI  - Anaesthesia with the difficult airway.

PMID- 9244040
TI  - Long-term outcome after percutaneous dilational tracheostomy.

PMID- 9244041
TI  - Percutaneous tracheostomy; an expensive complication.

PMID- 9244042
TI  - Central venous line sepsis.

PMID- 9244043
TI  - Central venous line sepsis.

PMID- 9244044
TI  - Bier's block.

PMID- 9244045
TI  - Bier's block.

PMID- 9244046
TI  - The value of continuous practice.

PMID- 9244047
TI  - The Bosworth introducer and the flexible reinforced laryngeal mask airway.

PMID- 9244048
TI  - Occupational exposure to inhalational anaesthetics.

PMID- 9244049
TI  - Remifentanil and cholinesterase.

PMID- 9244050
TI  - Accidental bronchial intubation.

PMID- 9244051
TI  - Accidental bronchial intubation.

PMID- 9244053
TI  - Patient-controlled regional anaesthesia.

PMID- 9244054
TI  - Heparin prophylaxis and central neural blocking techniques.

PMID- 9244055
TI  - Spinal cord injury due to haematomyelia.

PMID- 9244056
TI  - The potential for extravasation using a new five lumen catheter.

PMID- 9244057
TI  - Use of a pulse oximeter during performance of an axillary plexus block.

PMID- 9244058
TI  - Analgesia for removal of chest drains.

PMID- 9244059
TI  - Trauma and throat packs.

PMID- 9244060
TI  - Trauma and throat packs.

PMID- 9244061
TI  - Nasogastric contents short-circuit pressure transducer.

PMID- 9244062
TI  - 'Doctor, my ear is painful'.

PMID- 9244063
TI  - The Annals July 1997: 50 years young.

PMID- 9244064
TI  - Colostomy in conflict: military colonic surgery.

PMID- 9244065
TI  - Gene therapy and cell engineering.

PMID- 9244066
TI  - Dual-energy X-ray absorptiometry predicts bone formation in lower limb callotasis
      lengthening.
AB  - The rate of regenerate bone mineral content (BMC) acceleration was studied using
      dual-energy X-ray absorptiometry (DEXA) in callotasis lengthening of the lower
      limb. Eleven youngsters (age range 5-17 years) undergoing callotasis lengthening
      for congenital, post-traumatic or post-infective conditions were studied
      longitudinally. Patients were initially scanned once a week until completion of
      the lengthening phase, and at 2-week intervals thereafter until removal of the
      fixator. They were subsequently followed up at regular intervals on an outpatient
      basis for up to 2 years after removal of the fixator (average, 14 months). The
      BMC accretion slopes exhibited by the patients and the rate of new bone formation
      allowed the identification of three groups. In the fast formation group, the rate
      of new bone formation was 0.3-0.6% per day. In the moderate formation group the
      rate of new bone formation is 0.1-0.3% per day, while in the poor formation group
      the rate of new bone formation is < 0.1% per day. From the analysis of time
      graphs, a direct correlation emerged between early bone formation and subsequent
      bone mineral content accretion. Measurement of BMC during callotasis lengthening
      in the lower limb allows precise monitoring of the process. It may prove useful
      to prevent complications occurring after removal of the fixator at an unduly
      early stage, such as plastic deformation and fracture through the regenerate
      bone. It may be used to predict the bone formation rate in a given patient, and
      to implement measures to try to influence it.

PMID- 9244067
TI  - Infusion pumps for systemic and intra-arterial chemotherapy of colorectal liver
      metastases.
AB  - Over a 12 month period, we prospectively evaluated the use of an ambulatory
      infusion pump for intra-arterial and intravenous chemotherapy in patients with
      colorectal liver metastases. In all, 274 separate infusions were given with minor
      complications occurring on six occasions. Administering treatment on an
      outpatient basis rather than as an inpatient has resulted in savings of over
      Pounds 17000 in the first year.

PMID- 9244069
TI  - Intermittent claudication should not be treated by surgery.
AB  - This debate examines the proposition that surgery is unnecessary or obsolete in
      the management of intermittent claudication. The case for this argument is that
      many patients have stable disease or respond well to conservative measures, that
      claudication is an expression of a systemic cardiovascular illness and that
      surgery can be replaced by endovascular techniques with equal success, and less
      disadvantage in the event of treatment failure. The case against the motion is
      that claudication is associated with repeated cycles of ischaemia and
      reperfusion, and that these contribute to excess cardiovascular mortality states
      and, furthermore, that surgery is the only option to relieve symptoms for many
      patients, especially those with distal disease.

PMID- 9244068
TI  - Surgery for periampullary and pancreatic carcinoma: a Liverpool experience.
AB  - The development of a single-surgeon specialist referral practice for pancreatic
      surgery which evolved over an 8 year period is described. Source of referral,
      protocol for patient management, and operative strategy are outlined.
      Preoperative endoscopic retrograde cholangiopancreatography (ERCP), endoscopic
      sphincterotomy, and stent placement where possible (85% of cases), high
      resolution contrast-enhanced CT and standard pylorus-preserving
      pancreaticoduodenectomy with a unique reconstructive technique were employed. In
      105 patients receiving curative resection for pancreatic or periampullary
      tumours, the overall operative mortality was 4.8% and overall morbidity 26%.
      Actuarial 5-year survival rates were 11% for pancreatic carcinoma and 34% for
      ampullary carcinoma. Resectability rate was 81% without the use of time-consuming
      and expensive imaging techniques for staging such as laparoscopy, intraoperative
      ultrasound or laparoscopic ultrasound. No specific regimen of perioperative
      chemoirradiation was utilised over the study period. To achieve comparable
      results it is recommended that patients should be referred to regional specialist
      surgeons in whose hands mortality and morbidity is low, costs reduced and
      training of pancreatic surgeons can be undertaken.

PMID- 9244070
TI  - Immediate cytodiagnosis and imaging in the clinical management of discrete benign
      breast lesions.
AB  - Benign breast disease accounts for the majority of referrals to a specialist
      breast clinic. Delayed investigation prolongs patient anxiety and increases
      outpatient waiting lists. Few centres offer the triple test of clinical
      examination, fine needle aspiration cytology (FNAC) and breast imaging by
      mammography and/or ultrasonography at initial presentation. We have analysed the
      practicality of such a service during the 12 months following its introduction in
      our district general hospital. We studied the cohort of 178 patients who
      presented with a discrete breast lump which was subsequently shown to be benign.
      A triple test was performed in 72% of all patients. In 100 patients (56%) this
      was performed at initial assessment. Of these, 87 had clinically benign disease
      confirmed by FNAC and breast imaging and they were informed of the results within
      3 h. A triple assessment during the initial consultation allows the majority of
      patients with discrete benign breast disease to be given immediate reassurance.

PMID- 9244071
TI  - A comparative audit of prevalent, incident and interval cancers in the Avon
      breast screening programme.
AB  - The 4th year of the Avon breast screening programme comprises two distinct
      groups: those called for screening for the first time (prevalent group) and those
      who were initially screened 3 years earlier (incident group). The cancer
      detection rate, stage of disease and rate of interval cancers in these patients
      have been compared. For the prevalent groups of year 1 and year 4 there was no
      statistically significant difference in the cancer detection rate, proportion of
      small tumours or node positivity. For the prevalent and incident groups of year
      4, there was no statistically significant difference in the cancer detection rate
      or proportion of small tumours. There were significantly fewer node-positive
      tumours in the incident group (5/45 vs 8/23; P < 0.05). Fifty-six interval
      cancers presented in the 3-year period between years 1 and 4 of screening; 28
      (50%) after 24 months. The screening programme may result in tumours being
      detected at an earlier stage, but this may be offset by the high rate of interval
      cancers. This suggests that the time between screens may need to be reduced to 2
      years.

PMID- 9244072
TI  - Rate and classification of interval cancers in the breast screening programme.
AB  - There has been concern about the number of interval cancers which have been
      detected within the National Breast Screening Programme. A series of 134 women
      presenting with interval cancers was studied by prospective audit and the rate
      and radiological classification of the tumours determined. The cancers were
      classified as true (67), false-negative (22), unclassifiable (28), occult (12),
      and minimal sign (5). The interval cancer rate did not achieve the new National
      Guidelines in either the first 2 years or the 3rd interval year. The false
      negative cancers presented mainly in the 1st interval year, whereas the true
      cancers were predominantly confined to the 2nd and 3rd years. These data suggest
      that alterations to the screening programme may be beneficial. It may be,
      however, that the programme is still on the learning curve and this should be
      taken into account when interpreting these data.

PMID- 9244073
TI  - Microvascular reconstruction of complex craniofacial defects.
AB  - Many large vault or skull base tumours are best treated by wide surgical excision
      and primary reconstruction using a microvascular free tissue transfer (free
      flap). We report 23 patients who were reconstructed using free flaps, eight
      having been previously treated surgically elsewhere and seven of whom had
      recurrent disease after radiotherapy. There was one flap failure and a local
      recurrence rate of 16% (3/19). The outcome at a mean follow-up period of 29
      months, was 19 patients alive and four deaths.

PMID- 9244074
TI  - Length of postoperative hospital stay after transurethral resection of the
      prostate.
AB  - The aim of the study is to explore the value of audit in investigating and
      reducing the length of stay (LOS) of patients after transurethral resection of
      the prostate (TURP). All TURPs in a district general hospital (DGH) were audited
      over 30 weeks. Particular attention was paid to patients whose LOS was longer
      than the average for the group (mean: 6.4 nights; median: 5 nights). Older age of
      the patient, larger resections and late removal of suprapubic catheters were
      statistically significant in prolonging LOS (P < 0.001). General anaesthesia was
      associated with longer stay than regional anaesthesia, but the difference was not
      statistically significant. Among patients whose LOS exceeded the average of 6
      nights, social circumstances and detrusor underactivity were the most important
      causes of late discharge, accounting for 44% (28/63) of these cases. Where
      factors were avoidable, changes were implemented. Increased use of regional
      anaesthesia was encouraged. Catheters were removed earlier, and discharges,
      whenever possible, were pre-planned. A re-audit was carried out 1 year after the
      original audit and a significant decrease in LOS was found (mean: 5.2 nights;
      median: 4 nights; P < 0.01). Audit can increase awareness of prolonged hospital
      stay and highlight areas for change. Re-audit can confirm the effectiveness of
      these changes.

PMID- 9244075
TI  - Provision of a day case abscess service.
AB  - We have established a day case service for the surgical treatment of superficial
      abscesses and present the results of our first 100 patients. We feel that this is
      an efficient and safe service with 92% treated within 6 h of arrival in hospital
      and no complications in this series of patients. It has important implications
      for the management of this common surgical problem.

PMID- 9244076
TI  - Demand on primary health care after day surgery.
AB  - We have audited the frequency and nature of demands made on general
      practitioners, and the rate of surgical and anaesthetic complications within the
      first 7 days after day surgery. Semi-structured questionnaires were posted to the
      general practitioners of patients who attended the hospital's day care ward for a
      surgical procedure over a 6 month period. In all, 1798 questionnaires were sent,
      of which 1533 (85.3%) were returned. A total of 247 (16.7%) patients consulted
      their general practitioners after day surgery, the principal reason being pain
      (113 patients). Patients who underwent incisional intermediate surgery had the
      highest rate (31.5%) of general practitioner consultations. This audit has
      quantified the workload which day surgery places upon general practitioners. It
      also demonstrates the importance of categorising the various procedures performed
      on a day case basis when examining patient outcome. Patients who underwent non
      incisional minor surgery consulted their general practitioner less often than
      those who underwent incisional minor surgery, who in turn consulted their
      practitioner less often than those who underwent incisional intermediate surgery.
      It seems likely that an increase in workload for general practitioners is
      inevitable if more complex procedures are performed on a day case basis.

PMID- 9244077
TI  - An audit of theatre scrubrooms in a district general hospital.
AB  - While much has been written on surgical theatre design, little can be found on
      the design of theatre scrubrooms. An audit of theatres at a modern district
      general hospital (DGH) revealed that only one scrubroom had the minimum free
      floor space required and none complied with other baseline parameters. A survey
      of surgeons revealed that 60% had to re-scrub because their hands had
      desterilised through insufficient scrubroom space. The implications for hygiene
      hazards are clear. We review the literature and outline the basic dimensions
      which should be incorporated in the design of modern theatre scrubrooms.

PMID- 9244078
TI  - Perioperative blood transfusion: a plea for guidelines.
AB  - Red blood cells are still transfused inappropriately in spite of recent media
      attention and public awareness about the risks of blood products. A prospective
      audit was conducted to determine the avoidable blood transfusion rates in the
      elective perioperative setting utilising the guidelines issued by the American
      College of Physicians (ACP). Of 82 consecutive adult patients who were admitted
      for major elective surgery over a 3-month period, 28 were transfused a total of
      94 units of homologous SAG-M blood, of which 50 (53%) were inappropriate as
      recommended by the ACP guidelines. Violations of the guidelines were
      perioperative transfusion in bleeding patients who were haemodynamically stable
      (31%) and transfusion in asymptomatic, stable patients solely to attain a
      haemoglobin level above 10 g% (22%). There is a need for objective, easily
      adaptable and widely disseminated consensus guidelines to the indications for red
      blood cell transfusion.

PMID- 9244079
TI  - Randomised trial of subcuticular suture versus metal clips for wound closure
      after thyroid and parathyroid surgery.
AB  - A randomised trial was conducted to compare the results of neck wound closure
      using metal (Michel) clips or subcuticular suture. All operations were performed
      using a standardised technique, which included wound infiltration with 10 ml
      bupivacaine and adrenaline solution, no strap muscle division and the use of
      suction drains. All the collar incisions and wound closures were performed by the
      same surgeon. At the end of each operation patients were randomised to wound
      closure by either metal clips (n = 38) or a continuous 3/0 prolene subcuticular
      suture (n = 42). Daily postoperative pain scores and the discomfort caused by
      clip/suture removal were recorded. The cosmetic appearance of each wound was
      scored by the patient, the surgeon, and an independent observer using verbal
      response and linear analogue scales. The two study groups were well matched for
      age, sex, indication for surgery and operation performed. There were no
      differences in postoperative pain scores between clips and sutures. Removal of
      subcuticular sutures was performed more quickly (P < 0.0001) and caused less pain
      (P < 0.0001, visual analogue scale; P = 0.0042, verbal response scale) than the
      removal of clips. At the time of discharge, the cosmetic appearance scores
      generated by the surgeon, patient and independent observer were higher for suture
      closed wounds than clips. However, by 3 and 6 months follow-up there were no
      differences in cosmetic appearance between the two methods of closure. Only very
      short-term cosmetic results are influenced by the type of wound closure in
      thyroid and parathyroid surgery, but sutures are quicker and less painful to
      remove than Michel clips.

PMID- 9244080
TI  - The Didcott dilator.

PMID- 9244081
TI  - Iatrogenic accessory nerve injury.

PMID- 9244082
TI  - The place of duplex scanning for varicose veins and common venous problems.

PMID- 9244083
TI  - The endovascular revolution.

PMID- 9244084
TI  - Pathogenesis, clinical features and management of hidradenitis suppurativa.

PMID- 9244085
TI  - Pathogenesis, clinical features and management of hidradenitis suppurativa.

PMID- 9244086
TI  - A useful sign for the diagnosis of peritoneal irritation in the right iliac fossa
      and Can serum interleukin-6 levels predict the outcome of patients with right
      iliac fossa pain?

PMID- 9244087
TI  - The case against a national screening programme for aortic aneurysms.

PMID- 9244090
TI  - Post-burn reconstruction during growth and development.
AB  - Modern plastic and reconstructive surgery continues to significantly improve the
      functional and aesthetic post-burn sequelae in children. It has become a major
      factor in restoring mobility, aesthetic appearance, self-esteem, and quality of
      life. The entire spectrum of plastic reconstructive procedures should be
      available to offer the patient an optimal solution to his problems. Therefore,
      early interdisciplinary co-operation between pediatric and plastic surgeons is
      mandatory to plan and perform post-burn reconstruction in children and
      adolescents.

PMID- 9244089
TI  - The cornerstones and directions of pediatric burn care.
AB  - Active basic-science investigations and directed clinical research have resulted
      in effective therapies for improving the outcomes of burned children. Major areas
      of inquiry have been in resuscitation, hypermetabolism, wound coverage, and
      inhalation injury, all of which have yielded fruitful results. Probably the most
      important advance has been the widespread use of early excision and grafting,
      which has changed the pathophysiology of burn injury. Further advances in the
      fields of metabolism, wound healing, and respiratory medicine may improve results
      even further, particularily in functional and cosmetic outcomes.

PMID- 9244092
TI  - Spiral computed tomography with 3-dimensional reconstruction for the diagnosis of
      tracheobronchial stenosis.
AB  - We report on the usefulness of spiral computed tomography (CT) with 3-dimensional
      (3D) reconstruction in the diagnosis of tracheobronchial abnormalities based on
      three cases of children with congenital tracheobronchial strictures. Images were
      reconstructed using a curved planar reformat and shaded surface display. The
      images obtained from our three cases of tracheal stenosis, subglottic stenosis
      and tracheobronchial strictures were extremely clear. Spiral CT with 3D
      reconstruction provides excellent anatomic delineation of the tracheobronchial
      airway, and is safe and less invasive than tracheobronchography.

PMID- 9244093
TI  - Experience with modified posterolateral muscle-sparing thoracotomy in neonates,
      infants, and children.
AB  - Between May 1991 and December 1995, a total of 38 posterolateral muscle-sparing
      thoracotomies were performed in neonates and children. The technique described
      preserves the serratus anterior and most of the latissimus dorsi muscle. In all
      except 1 case, excellent exposure of the thoracic cavity was achieved. The muscle
      sparing approach is easy to perform with appropriate attention to the anatomy of
      the chest wall. It has the advantages of minimal anatomic disturbance and trauma
      to the major chest-wall muscles, and hence is likely to be associated with less
      postoperative pain and, possibly, improved pulmonary function. A plea for routine
      use of a muscle-sparing incision for thoracotomy procedures in the pediatric age
      group is thus justifiable.

PMID- 9244091
TI  - Anesthesia and pain management in pediatric burn patients.
AB  - Patients with severe burn injury are a challenge for the pediatric
      anesthesiologist. Today with adequate care many children survive their trauma and
      have a good chance for complete functional and psychological rehabilitation. The
      anesthesiologist has to provide excellent care even for patients in suboptimal or
      unstable condition to enable wound debridement and grafting, because only rapid
      skin closure will stabilize the patient. Adequate pain treatment during all
      phases of burn treatment is mandatory.

PMID- 9244094
TI  - Electrogastrography after operative repair of esophageal atresia.
AB  - Esophageal atresia (EA) is a life-threatening disorder associated with operative
      complications. Postoperative gastric electrical control activity detected by a
      non-invasive electrogastrography (EGG) technique was investigated in 13 children
      aged 1-17 years to clarify whether gastric motility disorders were present. EGG
      abnormalities were present in 5 patients; persistent dysrhythmias were found in
      3. Roentgenographic examinations showed mild gastroesophageal reflux in 3 (60%)
      of the dysrhythmic patients; 2 others had postprandial dysrhythmias. The mean
      spectral frequency (MSF) of EA cases with dysrhythmia was significantly higher
      than that of patients without dysrhythmia in both fasting and postprandial states
      (P < 0.05). The variability of the peak spectral frequencies (PSFV) in patients
      with dysrhythmia was significantly higher than in those without dysrhythmia in
      both fasting and postprandial states (P < 0.05). There were no significant
      differences in MSF and PSFV between EA patients without dysrhythmia and controls.
      These results suggest that gastric motor activity may be disordered in patients
      following operative repair of EA, although they remain asymptomatic. EGG may be a
      useful screening examination for postoperative gastric functional disorders.

PMID- 9244095
TI  - Ultrasonographic evaluation of gastric emptying in normal children and children
      after pyloromyotomy.
AB  - Gastric emptying in the fundus, body, and antrum of the stomach was evaluated by
      ultrasonography (US) in 41 control children aged 2 to 18 years and 30 patients
      aged 1 to 19 years who had undergone pyloromyotomy because of hypertrophic
      pyloric stenosis. The gastric emptying curve decreased in an exponential manner
      for both control children and patients, while there was no significant difference
      in gastric emptying time (GET) between control children and patients within any
      of the age groups. However, GET was faster for younger children in both groups.
      An X-ray contrast study of the stomach performed in 2 patients who showed
      markedly delayed GET showed delayed gastric emptying but no significant
      deformities of the prepylorus. Our results suggest that US is a reliable method
      of measuring GET in children.

PMID- 9244096
TI  - Trends in management of gallbladder disorders in children.
AB  - Gallbladder disorders have been recognized with increasing frequency in pediatric
      patients. This study aimed to identify recent trends in management and compare
      the effectiveness of laparoscopic (LC) over open cholecystectomy (OC) by a
      retrospective chart analysis of all cholecystectomies from 1990 through 1995.
      Information obtained included demographics, symptoms, predisposing conditions,
      associated illnesses, family history, imaging studies, type of cholecystectomy,
      complications, operative time, pain medication, diet recommencement, pathologic
      findings, and length of hospital stay. The type of cholecystectomy (OC vs. LC)
      was compared with the clinical variables using standard statistics. Eighty-three
      patients between 21 months and 18 years of age were identified; their mean age
      was 14.8 years. Females (76%) with classic biliary symptoms predominated;12% of
      the patients developed gallstone pancreatitis and 7% jaundice. Abnormal liver
      chemistry values, obesity, and elevated triglyceride levels comprised the most
      significant predisposing factors. Indications for surgery were cholelithiasis in
      71 patients (86%), gallbladder dyskinesia in 10 (12%), and sludge/polyp in 2.
      Fifty-nine cholecystectomies (71%) were done laparoscopically and 24 (29%) open.
      Choledocholithiasis in 6 children (7%) was managed by open extraction with t-tube
      placement or endoscopic papillotomy followed by LC. No major ductal complication
      was identified. The predominant pathologic finding was chronic cholecystitis,
      including the subgroup with biliary dyskinesia. Statistical comparison showed
      that LC is superior to OC in regard to length of stay, diet resumption, use of
      pain medication, operating time, and cosmetic results. It is concluded that a
      contemporary diet, obesity, and abnormal liver chemistry are the main
      predisposing conditions of gallbladder disease in children in this decade.
      Females in their teenage years with typical symptoms continue to be the most
      commonly affected group. Persistent biliary symptoms associated with low
      gallbladder ejection fractions during hepatobiliary cholecystokinin-stimulated
      scans can be caused by dyskinesia. The method of choice to remove the diseased
      gallbladder in children is LC, which is safe, efficient, and superior to the
      conventional method. Common duct stones can be managed by simultaneous endoscopic
      papillotomy. The costs of LC are reduced by employing reusable equipment and
      selective cholangiographic indications.

PMID- 9244097
TI  - Conservative surgery for benign non-parasitic splenic cysts.
AB  - Benign, non-parasitic splenic cysts are an uncommon cause of splenomegaly in
      children. Potentially they may enlarge, causing pain, rupture, or haemorrhage, or
      become infected. Traditional management has been total splenectomy. We report two
      cases of true epithelial-lined splenic cysts successfully treated by partial
      splenectomy using an oxidised cellulose gauze 'sandwich' technique.

PMID- 9244098
TI  - Laparoscopic and thoracoscopic surgery in children and adolescents: a 3-year
      experience.
AB  - Our initial experience over the last 3 years with laparoscopic and thoracoscopic
      surgery in children and adolescents is reported. Between September 1992 and
      August 1995, a total of 215 laparoscopic and thoracoscopic procedures were
      performed: 32 appendectomies for acute appendicitis, 10 cholecystectomies for
      symptomatic gallstones, 11 procedures for adnexal pathology, 6 laparoscopies in
      children with nonpalpable testes, 3 diagnostic laparoscopies, and 153
      thoracoscopic sympathectomies in children suffering from primary palmar
      hyperhidrosis. The post-operative course was uneventful in all cases. In 2
      children with acute appendicitis we converted to the open technique due to
      technical difficulties. We are encouraged by the results of our initial
      experience. There is no doubt that laparoscopic cholecystectomy, laparoscopic
      surgery of adnexal pathology, and thoracoscopic sympathectomy, because of their
      numerous benefits - shorter operative time, hospitalization, and convalescence as
      well as less postoperative pain and improved cosmetic results - are replacing the
      open techniques. We are not convinced as yet of the advantages of laparoscopic
      appendectomy in children; we are presently performing both laparoscopic and
      conventional techniques and studying the various parameters in order to reach a
      more definite conclusion. Various other endoscopic surgical procedures will be
      carefully considered in the near future.

PMID- 9244099
TI  - Blockage of mesenteric lymphatic flow in rats.
AB  - An experimental model of blockage of the mesenteric lymphatic flow (MLF) in rats
      was designed, and morphologic changes of mesenteric lymphatic vessels (MLV) and
      lymph nodes were investigated by mesenteric lymphangiography and histopathologic
      examination. Body weight in rats with blockage of MLF did not increase normally.
      Mesenteric lymphangiography revealed dilation of the MLV, reverse flow into the
      peripheral MLV, and leakage of contrast medium, resulting in chylous ascites.
      Remarkable dilation of the lymphatic sinuses and dilated and increased rough
      endoplasmic reticulum in lymphocytes in the mesenteric lymph nodes due to lymph
      stagnation were observed by light and electron microscopic examination,
      respectively.

PMID- 9244100
TI  - Isolated bowel segment created by omentoenteropexy: histologic findings.
AB  - An isolated bowel segment (IBS) is a viable loop of bowel that is completely free
      of its mesenteric attachments. In this study, omentoenteropexy (OEP) was
      performed in 5-cm-long IBS of rats in order to provide neovascularization. Thirty
      two rats were divided into four groups. After OEP, mesenteric division of the
      IBSs was performed at successive 1 week intervals in each group (3-6 weeks). The
      bowel-wall structures were histologically examined 2 days after division of the
      mesentery. Ischemic changes were observed in the group in which the interval was
      shorter than 4 weeks. In the IBSs that were supplied by the pediculated omental
      flap for 4 or more weeks no ischemic changes were noted in the mucosa, muscle
      layers, or intramural ganglia. We conclude that an IBS that preserves normal
      bowel structures can safely be created in the rat when its mesentery is divided 4
      weeks after OEP. Physiological studies of motility and absorption can be
      performed and longitudinal tubularization may enable such an IBS to be used in
      short-bowel syndrome.

PMID- 9244101
TI  - Fetal intestinal transplant as an accessory enteral segment.
AB  - Fetal tissue transplantation has gathered considerable interest among researchers
      dealing with organ transplantation. A large number of studies concerning fetal
      intestinal transplantation have been published in the past 2 decades, almost all
      of them aiming to determine the feasibility of a properly functioning fetal
      transplant in continuity with the host's own enteral system. This study was
      designed to determine the absorptive capacity of the neogut in vivo, without
      anastomosing the transplant to the host's intestine, and to evaluate its use as
      an accessory enteral segment. Intestinal segments taken from Wistar albino
      fetuses were transplanted subcutaneously into the abdominal wall of 20 Sprague
      Dawley rats. Immunosuppression was maintained by daily cyclosporin A (Cy A) 10
      mg/kg injections s.c. and evaluated by determination of serum Cy A level and T
      helper/T-suppressor cell ratio. The neogut was converted into a Thiry-Vella loop
      2 weeks after transplantation. A test solution composed of 20% glucose and
      Trophamine was perfused via the stomas; glucose and amino acid absorption
      gradients were calculated. The gamma-glutamyl transferase (GGT) activity and
      mitotic index of the neogut were determined. Results were compared to those
      obtained from the host. There was no significant difference (P > 0.05) in glucose
      absorption between the neogut and the host tissue. Amino acid absorption and
      specific GGT activity were significantly less (P < 0.01) in the neogut. There was
      no significant difference (P > 0.05) between neogut and host intestine in mitotic
      index. Our data support the idea of using a transplanted fetal intestinal segment
      as an accessory feeding route.

PMID- 9244102
TI  - Length of transplanted small bowel required for adequate weight gain in rats.
AB  - Progress has been made toward developing a clinically successful small-bowel
      transplant procedure, but there has been little research concerning the
      functional aspects of the transplanted small bowel. Using a rat model, our study
      examined the length of transplanted small bowel required to provide adequate
      weight gain. The rats were divided into six groups; groups 1 and 2 were
      considered controls. Group 1 (n = 6) underwent a gastrostomy. Group 2 (n = 3)
      underwent a jejunoile-ectomy followed by re-establishment of intestinal
      continuity and anastomosis of the native proximal small bowel to an abdominal
      stoma and the distal portion to the ascending colon. Groups 3 (n = 5), 4 (n = 4),
      5 (n = 5), and 6 (n = 4) underwent small-bowel transplantation, receiving 100%,
      50%, 25%, and 15% transplants, respectively. The donor small-bowel anastomoses
      were the same as the native small-bowel anastomoses in group 2. All of the rats
      began to produce stool within 4 days of becoming dependent upon the transplanted
      small bowel. By the end of postoperative week 4, there was no significant
      difference between the percentages of preoperative body weight in groups 1-4
      (range 125.7%-130.0%). Although the weight gain in group 5 was significantly less
      than that in groups 1-4 (P < 0.05), it was adequate (111.8%); group 6 animals
      lost weight (94.7%). It is concluded that a 50% or more small-bowel transplant
      with or without an ileocecal valve provides ample weight gain; minimally adequate
      weight gain is achieved by a 25% transplant without an ileocecal valve; and the
      graft begins to function soon after transplantation.

PMID- 9244103
TI  - Intussusception in the 1990s: has 25 years made a difference?
AB  - To evaluate the current management of the infant and child with intussusception,
      the medical records of 188 consecutive intussusception patients over 5 years
      (1985-1990) were reviewed and compared to our series from 25 years ago (1959
      1968). The peak months changed from May and June to January and July. Duration of
      symptoms and signs prior to diagnosis increased by one-third to 35 h with,
      however, a decrease in the incidence of pain, vomiting, abdominal mass, and
      rectal blood. Air was the only contrast used for the hydrostatic enema in the
      present series and was tried in every case with 81% success; this is a major
      improvement from 45% in the old series. There were three perforations (1.4%) with
      air-enema attempts compared with 1 (0.2%) 25 years ago. Recently only 19% of
      patients required operation but 30% needed resection; 55% of the patients in the
      older series required operation and 20% needed resection. Ten percent of
      intussusceptions continue to be found spontaneously reduced at operation. There
      were many less pathologic lead points in the newer series. The recurrences
      increased from 4% to 7%, but their reduction rate also increased from 31% with
      barium to 100% with air. There were no deaths in the last 25 years.

PMID- 9244105
TI  - The use of augmented-pressure colostography in imperforate anus.
AB  - Colostomy is recommended in most newborns with imperforate anus (IA), except
      those with low-type anorectal malformations (ARM). Accurate demonstration of the
      anatomy of any associated fistula between the rectum and the urogenital tract is
      essential for optimal surgical management. Augmented-pressure distal
      colostography is recommended to fulfill this requirement prior to definitive
      surgical repair of IA. We examined 12 cases of high or intermediate-type ARM
      using this technique, which clearly demonstrated the distal perineal anatomy. All
      were confirmed at posterior sagittal anorectoplasty.

PMID- 9244104
TI  - Clinical impact of intestinal neuronal malformations: a prospective study in 141
      patients.
AB  - A prospective study of 141 consecutive patients with intestinal neuronal
      malformations is presented. The single malformation of the autonomic nervous
      system that always required surgical intervention was aganglionosis. Giant
      ganglia, reduced parasympathetic tone, immature ganglia, and hypogenetic or
      heterotopic nerve cells were seen in all forms of malformations. However, the
      incidence in specific malformations was variable. Multiple giant ganglia were
      identified in all patients with intestinal neuronal dysplasia (IND) type B, but
      also in various other malformations. Heterotopic nerve cells in the myenteric
      plexus were seen in the proximal segment of 15 of 74 patients (20.3%) with
      aganglionosis and 5 of 9 patients (55.6%) with hypoganglionosis. A significant
      impact on symptoms was found for IND type B: 34 (45.9%) of 74 children with
      aganglionosis had associated IND type B, and these children more frequently
      developed ileus (P < 0.001) and more often needed a second resection (P < 0.05)
      compared to those with isolated aganglionosis. This indicates an additive effect
      of both malformations, and therefore, in these patients an extended resection
      should be carried out. Twelve of 67 patients (17.9%) without aganglionosis needed
      resection for untreatable constipation. This included 7 of 9 children with
      hypoganglionosis, both patients with heterotopia of the myenteric plexus, 1 of 20
      with isolated IND type B, and 2 of 12 with reduced parasympathetic tone. None of
      the patients with immaturity, heterotopia of the submucous plexus, or mild
      dysganglionosis required surgery. Six children (8.9%) without aganglionosis
      underwent sphincteromyotomy and 2 with IND type B had a temporary colostomy. At
      follow-up (mean 2.4 +/- 1.4 years), the outcome in patients with resected
      aganglionosis was better than in patients who had resections for other
      malformations; 49 (69%) of 71 patients with aganglionosis were asymptomatic
      compared to 4 (33.3%) of 12 with other malformations (P < 0.05). It is concluded
      that some intestinal malformations have a relevant clinical impact. However, the
      severity of symptoms in the individual patient may not be explained by specific
      histochemical findings from a limited number of mucosal biopsies. The
      pathognomonic histochemical criteria of isolated IND type B - immaturity, reduced
      parasympathetic tone, heterotopia of the submucous plexus, and mild
      dysganglionosis - rarely require surgical therapy and should be treated
      conservatively.

PMID- 9244106
TI  - Mucosal plication in the treatment of partial rectal prolapse.
AB  - A technique used for the treatment of 34 patients with partial rectal prolapse
      [20 children (mean age 4.2 +/- 1.4 years), 10 women, and 4 men (mean age 44.6
      years)] is presented. The prolapsed mucosa protruded outside the anus in 26
      patients and was inside the rectal neck in 8. Mucosal plication was performed;
      the prolapsed mucosa was reefed by multiple vertical pursestring sutures.
      Associated hemorrhoids and anal fissures were also corrected. The patients were
      followed up for a mean of 31.6 months. No straining at stool or recurrence of the
      mucosal prolapse occurred. The technique is simple, cost-effective, had no
      complications, and was performed on an outpatient basis.

PMID- 9244107
TI  - Non-intubated pyeloplasty for pelviureteric junction obstruction in children.
AB  - Sixty-one consecutive patients undergoing pyeloplasty (5 bilateral) were reviewed
      retrospectively; 54 pyeloplasties were non-intubated (NIP) and 12 were intubated.
      NIPs were managed by an extrarenal wound drain, which was removed after 2-4 days
      in 44 repairs with minimal or no urinary leakage and after 6-8 days in 10 with
      significant leakage. Fifty-two were successful after the primary procedure. One
      patient who developed a urinoma after drain removal required a percutaneous
      nephrostomy followed by a revision pyeloplasty. A second revision pyeloplasty was
      necessary for persistent postoperative obstruction. The results of NIP compared
      favorably with series where intubation was used routinely and were superior to
      alternative methods of management such as endopyelotomy.

PMID- 9244108
TI  - Stomach versus sigmoid colon in children undergoing major reconstruction of the
      lower urinary tract.
AB  - A review of 50 patients who underwent intestinocystoplasty (ICP) or
      gastrocystoplasty (GCP) replacement at our department during an 8-year period is
      presented. The most common diagnoses were neurogenic bladder and bladder
      exstrophy. A total of 48 patients underwent augmentation cystoplasty and 2 had
      total bladder replacement. Mean follow-up time was 42 months. The clinical and
      metabolic aspects of the two types of ICP are reported. Hyperchloremic acidosis
      requiring therapy was not encountered, although mild degrees were seen after
      sigmoid augmentation in 36% of patients. A dysuria-hematuria syndrome (DHS) was
      seen in 50% of the patients who underwent GCP. Operative mortality rate was nil.
      Significant surgical complications occurred in 36% of the patients. The overall
      success rate for ICP and GCP in this series was 79.15%. ICP gives effective
      results when used to increase the compliance of the lower urinary tract, but
      problems related to electrolyte absorption, stones, and mucus production are
      often encountered. In GCP electrolyte absorption is practically eliminated, so
      that this technique can be used in patients with renal damage. In addition,
      patients with a normal bladder plate (bladder exstrophy) can achieve normal
      voiding with time. The authors believe that patients must be made aware of the
      possibility of DHS and that this syndrome needs further investigation.

PMID- 9244109
TI  - Further observations on histological changes at the ureteroileal junction in
      ileal conduits.
AB  - Seventy-two ureteroileal anastomoses taken from ileal conduits removed from 62
      patients were examined histologically to characterize the range of mucosal and
      stromal changes at these sites. All 72 demonstrated variable amounts of
      subepithelial chronic inflammation and fibrosis. Other histological features
      included: cystic spaces lined by transitional epithelium (N = 29; 40%; average
      diameter 1.2 mm); cystic spaces lined by mixed intestinal/transitional epithelium
      (N = 5; 7%; average diameter 0.77 mm); and cystically dilated intestinal glands
      (N = 21; 29%; average diameter 0.24 mm). The latter were associated with
      overgrowth by transitional epithelium, which had prevented mucus drainage. Twenty
      one (29%) had mucus pools with no epithelial lining (average diameter 1.2 mm),
      and polypoidal protrusions into the lumen of the anastomosis were found
      containing mucus pools (N = 4; 6%; average diameter 1.4 mm), transitional-lined
      cysts (N = 5; 7%; average diameter 2.2 mm), and mixed intestinal/transitional
      lined cysts (N = 2; 3%; average diameter 2.5 mm). Focal rupture of dilated
      intestinal glands with interstitial pooling of mucus was not uncommon, and marked
      dystrophic calcification was found in 1 case within a large collection of
      extracellular mucus. This series confirms that inflammation, fibrosis, and
      glandular overgrowth by transitional epithelium are common occurrences at
      ureteroileal anastomosis sites. Subsequent gland rupture may result in sizable
      accumulations of interstitial mucus, and rarely in marked dystrophic
      calcification.

PMID- 9244110
TI  - Morphogenesis of the human external male genitalia.
AB  - The morphogenesis of the external genitalia of human fetuses (16-250 mm crown
      rump [CR] length, 6-26 weeks of gestation) obtained after medical termination of
      pregnancy were studied. Differential development (male/female) started after 50
      mm CR length (9 weeks). At that time the external genitalia consisted of a
      cylindrical genital tubercle 2 mm in length with a visible coronary sulcus and
      glans and genital swellings on either side. A groove on the ventral aspect of the
      genital tubercle extended to the coronary sulcus; the lateral boundaries of this
      groove separated to form the urethral folds. In male fetuses the free edges of
      the urethral folds fused, starting from the proximal end, to form a tunnel over
      the ventral aspect of the phallus. The pelvic urethra opened into this tunnel,
      slightly distal to its origin. The mesodermal tissue forming the genital
      swellings migrated ventrally and then medially. As medial migration started, the
      skin in the midline between the genital swellings was raised up as a skin fold,
      which subsequently, as the genital swellings migrated further, became elevated.
      The proximal part of the tunnel formed by fusion of the urethral folds (proximal
      to the point of entry of the pelvic urethra) also was compressed and pushed out
      as the genital swellings fused in the midline over the root of the phallus. These
      changes took place at between 80 and 110 mm CR length (12-13 weeks' gestation);
      at this stage the phallus appeared short and was bent ventrally. With further
      growth and caudal migration of the scrotum, the phallus lost its ventral
      curvature. The appearance of the external genitalia at different gestational ages
      bore a close resemblance to that in children with hypospadias. We therefore
      conclude that hypospadias can be explained on the basis of an embryological
      arrest due to the absence of the required stimulus for male phenotypic
      development at the appropriate time.

PMID- 9244111
TI  - Rare congenital abnormalities of the anterior urethra.
AB  - Congenital abnormalities of the anterior urethra other than hypospadias (valve,
      diverticulum, and megalourethra) are rare conditions and can be difficult to
      diagnose. Based on five recent cases of these urethral abnormalities, we review
      the embryology and the English literature, and have found reports of about 100
      cases of valve and diverticulum and 50 cases of megalourethra. For all these
      abnormalities, the clinical presentation depends on age and the diagnosis depends
      essentially on voiding cystourethrography, which must show the entire urethra,
      and careful urethroscopic examination.

PMID- 9244112
TI  - Assessment of adolescent varicocele.
AB  - Varicocele is the most important male factor responsible for decreased fertility
      potential in married couples. From March through June 1994, 2,470 school boys
      aged 10-20 years were examined to establish the incidence of consecutive grades
      of varicocele and to develop a protocol for diagnosis and treatment of
      adolescents with varicocele. Grade 1 varicocele was found in 18%, grade 2 in 12%,
      and grade 3 in 5% of the population examined. An original protocol of
      ultrasonographic (US) examination (previously verified by angioscintigraphy) was
      introduced to assess boys with clinically diagnosed varicocele. The volume of
      each testis, testicular volume decrease (TVD), pampiniform vein diameter (PVD),
      and basal (BBF) and maximum blood flow (MBF) velocities were measured in 625
      boys. In 74 cases a semen analysis was performed. The statistical analysis
      revealed that the presence of venous reflux and PVD correlated with the grade of
      varicocele. Decreases in testicular volume were highly dependent on the grade of
      varicocele, PVD, and BBF and MBF velocities. Analysis of the relationship between
      spermatic (boys over 17 years) and US findings revealed that the quality of
      spermatogenesis can be predicted by US examination in adolescents with
      varicocele. The authors recommend multiparametric US examination as a reliable,
      objective, and repeatable technique for establishing criteria for operative
      treatment in boys under 18 years of age with varicocele as well as for
      postoperative evaluation.

PMID- 9244113
TI  - Fluconazole for treatment of fungal infections of the urinary tract in children.
AB  - Two children with fungal urinary tract infections (UTI) were treated with
      fluconazole. One had bilateral megaureters, an almost non-functioning right
      kidney, and a moderately functioning left kidney because of severe vesicoureteric
      reflux. He underwent a ureteric reimplantation procedure but developed a fungal
      UTI postoperatively. The other child had bilateral refluxing megaureters, one of
      which appeared to open ectopically into the urethra. He acquired a fungal
      infection during intensive and prolonged antibiotic therapy for a bacterial UTI
      and septicaemia in the neonatal period. Both fungal infections were cured
      successfully. We recommend fluconazole as a safe and effective antifungal agent
      that may be used as a drug of choice for this difficult problem.

PMID- 9244114
TI  - Computed tomography-guided percutaneous needle aspiration of lung abscesses in
      neonates and children.
AB  - Lung abscesses in children often respond to conservative treatment. This is
      unlikely in children less than 7 years of age and in these surgery is associated
      with significant morbidity and mortality. We report a neonate and a 2.5 year old
      child successfully treated with percutaneous computed tomography guided
      aspiration of lung abscesses.

PMID- 9244115
TI  - Paraesophageal hernia in the neonatal period - another differential diagnosis of
      esophageal atresia.
AB  - Two neonates with paraesophageal herniae, both associated with gastric volvulus
      are reported. The presenting symptoms in both cases were highly suggestive of
      esophageal atresia. Radiologic examinations enabled the correct diagnosis to be
      made, and appropriate surgery was then instituted.

PMID- 9244116
TI  - Gallbladder pseudopolyp formation following percutaneous liver biopsy.
AB  - Following an unsuccessful liver biopsy in a 16-year-old girl in which only bile
      was obtained, a sonographic (US) study was performed. The findings were those of
      free fluid just adjacent to the gallbladder as well as a small intraluminal
      protrusion of the gallbladder wall. The US features of the gallbladder finding
      were consistent with a polyp. Gallbladder polyps are very rare in children,
      however, sporadic case reports do exist. An US study 24 h after the invasive
      procedure revealed complete regression of the free fluid; the gallbladder wall
      protrusion has disappeared. We suggest that the tip of the biopsy needle had
      penetrated the gallbladder wall and caused a bile leak. The needle penetration
      caused elevation of the inner wall layer at the entrance site, which was
      indistinguishable from the sonographic findings of a gallbladder polyp [1-4]

PMID- 9244117
TI  - Papillomatosis of the gallbladder in metachromatic leukodystrophy.
AB  - A 2-year-old boy who presented with a cystic gallbladder mass was found
      histologically to have metachromatic leukodystrophy. Diffuse hyperplasia of the
      gallbladder mucosa, multiple tendrillar fronds extending into the lumen,
      extensive papillomatosis, and the presence of large numbers of macrophages
      bearing metachromatic material confirmed the diagnosis. The child developed
      progressive degeneration of the central nervous system, refractory
      bronchopneumonia, and generalized muscular atrophy. A computed tomographic scan
      of the brain demonstrated hypodense areas of white matter suggestive of
      demyelination. This report describes the rare association of gallbladder
      papillomatosis with a storage disorder and reviews the relevant literature.

PMID- 9244118
TI  - Hepatic foreign body in a child.
AB  - The majority of foreign bodies (FBs) swallowed by children are passed
      spontaneously without event. Perforation of the intestine with migration to the
      liver is rare. A child with a needle in the right lobe of the liver is reported.

PMID- 9244119
TI  - Cantrell's pentalogy. Report of four cases and their management.
AB  - Four neonates with the uncommon Cantrell's pentalogy seen in our hospital within
      a 6-month period without any apparent factor in common are described, with a
      review of the world literature. The first case was diagnosed prenatally at 15
      weeks' gestation, the earliest intrauterine finding in the literature. The
      occurrence of imperforate anus with the syndrome, observed in one of the cases,
      has not been previously reported. Two were operated upon and only one of the four
      survived. This high mortality was confirmed by similar cases reported by other
      authors.

PMID- 9244120
TI  - Embryogenesis of a sac containing a Meckel's diverticulum.
AB  - The embryogenesis of a previously unreported mesothelial pouch containing a
      Meckel's diverticulum is presented.

PMID- 9244121
TI  - Prenatal diagnosis of the fetus with cystic fibrosis and meconium ileus.
AB  - The sonographic finding of hyperechoic or dilated fetal bowel raises suspicion of
      a number of prenatal disorders including meconium ileus (MI), meconium
      peritonitis, congenital infection, neoplasm, or chromosomal trisomy. These
      findings may also represent transient normal variants. The following case report
      details the evaluation of one pregnancy with abnormal intestinal echogenic
      findings on serial sonograms (US), to demonstrate inherent diagnostic
      difficulties in such a case. A diagnostic algorithm is presented to aid in the
      proper use of US and DNA mutation analysis for cystic fibrosis (CF), so that the
      cause of an abnormal abdominal US can be established earlier and more accurately
      than suggested by previous management schemes. Earlier fetal diagnosis may help
      to anticipate postnatal problems associated with CF/MI, and therefore provide
      more optimal clinical management of the affected fetus.

PMID- 9244122
TI  - Solitary intestinal fibromatosis: a rare cause of intestinal perforation in
      neonates.
AB  - Solitary intestinal fibromatosis (SIF) is very rare; only 9 cases have been
      described. A new case presenting unusually in a newborn is described and the
      previously reported cases are reviewed. SIF should be considered in the
      differential diagnosis of a newborn presenting with an intestinal perforation.

PMID- 9244123
TI  - Fortuitous diagnosis of cystic fibrosis at laparotomy for acute appendicitis.
AB  - Two children aged 11 and 9 years were operated upon for acute appendicitis and
      were discovered to have cystic fibrosis: the histologic pattern of the removed
      appendix was typical for this disorder. Appendicitis may thus be the first
      presenting sign of occult cystic fibrosis.

PMID- 9244124
TI  - Inflammatory pseudotumor of the retroperitoneum in a child.
AB  - Inflammatory pseudotumor is a rare, benign lesion of various organs and tissues
      that occurs in children and young adults. A case is reported in a 12-year-old boy
      in a retroperitoneal location with involvement of the left ureter and a
      thrombosis of left iliac vein. He underwent surgical resection. A local
      recurrence 6 months later was surgically cured.

PMID- 9244125
TI  - Colon carcinoma in the adolescent.
AB  - Carcinoma of the colon in the adolescent, although an uncommon disease, is
      usually virulent and has a poorer prognosis than in older patients. We report
      three cases of colon cancer in youngsters less than 19 years old. Two of them,
      who were diagnosed and treated early, are presently considered cured; the third
      died 3 months after surgery. All underwent surgery and adjuvant therapy. In an
      extensive review of the literature, we found a consensus as to the rarity,
      virulence and poor prognosis of colon cancer in the younger population. The
      commonest histological pattern is an aggressive, mucin-producing adenocarcinoma.
      Predisposing conditions include familial polyposis coli and ulcerative colitis.
      We also found that a low socioeconomic status could be a predisposing factor.
      Survival obviously depends on the extent of the disease at diagnosis, and the
      shorter the delay in diagnosis, the better the prognosis. The therapeutic
      approach must be aggresive in both surgery and adjuvant therapy; the goal must be
      early diagnosis, the reward being a possibility of cure, as seen in two of our
      three cases.

PMID- 9244126
TI  - Imperforate anus (anal agenesis) with rectal and sigmoid atresias in a newborn.
AB  - A male baby was born to a healthy mother after an uncomplicated 39-week
      pregnancy. He had finger and toe syndactyly, right hemidiaphragm eventration, and
      a high imperforate anus (anal agenesis). The kidneys and chromosomes were normal.
      A right transverse colostomy was done and 5 months later he underwent a posterior
      sagittal anorectoplasty (Pena procedure). An intermediate imperforate anus with
      no urethral fistula and a rectal atresia 2 cm proximal to the distal rectal pouch
      were found; the distal rectal pouch was resected and the standard Pena procedure
      completed. Dilatations were initiated 2 weeks postoperatively and continued until
      the colostomy was closed. Prior to closure of the colostomy, a distal colon
      loopogram demonstrated an obstruction in the sigmoid; constrast introduced via
      the rectum outlined the same obstruction separated by 2 cm. A low sigmoid atresia
      was then repaired. Three weeks later, a contrast loopogram showed a narrow but
      intact rectosigmoid anastomois, and the colostomy was closed. The anorectal
      dilatations were discontinued and he remains well at 7 years of age.

PMID- 9244128
TI  - Neonatal urinary ascites due to unilateral vesicoureteric junction obstruction.
AB  - A case of unilateral vesicoureteric junction obstruction presenting with ascites
      in a neonate managed successfully with serial ultrasonography and delayed primary
      reconstruction is described.

PMID- 9244127
TI  - Cystic rectal duplication: a rare cause of neonatal intestinal obstruction.
AB  - A case of cystic rectal duplication revealed on day 2 of life by a low intestinal
      occluding syndrome is reported. Radiologic imaging (ultrasonography, cystography,
      rectography) showed a large, retrorectal liquid formation in the pelvis and
      abdomen, with pelvic compression of the terminal alimentary canal and lower
      urinary tract. Magnetic resonance imaging demonstrated a liquid formation with
      clearly defined edges and no medullary involvement, thus ruling out the
      possibility of a previous meningeal hernia. Biological markers were within normal
      limits. On day 4, a 9 x 6-cm cystic rectal duplication was removed, followed by a
      temporary colostomy. Pathologic examination demonstrated typical rectal
      architecture with ciliated cells. Radiologic and clinical findings at 2-month
      follow-up were reassuring. This case report is exceptional for the following
      reasons: (1) As a rule, rectal duplications are relatively rare (70 cases
      reported in the literature); (2) The means of disclosing a neonatal rectal
      duplication is unusual (4 cases reported in the literature); (3) The volume of
      the malformation was considerable; and (4) Heterotopic ciliated epithelium was
      present.

PMID- 9244129
TI  - Megalourethra: a report of four cases and review of the literature.
AB  - Megalourethra is a rare congenital anomaly characterized by severe dilatation of
      the penile urethra. Four cases of congenital megalourethra were seen at Sir
      Padampat Mother and Child Health Institute, Jaipur, during the last 10 years.
      Three cases of scaphoid megalourethra had no other associated congenital
      anomalies and were treat-ed successfully without any complications, while one
      patient with a fusiform megalourethra had severe associated congenital anomalies
      and died. These cases are reported with a review of the literature.

PMID- 9244130
TI  - A new method for removal of metallic-ferromagnetic foreign bodies from the
      tracheobronchial tree.
AB  - Foreign-body (FB) aspirations account for a reasonable percentage of respiratory
      emergencies in young children. Whereas 67% of aspirated FBs are of organic
      origin, metallic-ferromagnetic FBs are observed less frequently. We report the
      use of a wire with a magnetic tip fitting into the working channel of a rigid
      bronchoscope for removal of ferromagnetic FBs from the tracheobronchial tree.

PMID- 9244131
TI  - The role of laparoscopy in the management of impalpable testes.
AB  - Both diagnostic and operative laparoscopy were used in the management of 68
      impalpable testes. Twenty-three were either vanishing or atrophied, and were
      associated with a precarious blood supply. Two were found in the groin, 12 in the
      inguinal canal, and 32 at variable distances from the internal ring; of these, 2
      were in a patient with persistent mullerian duct syndrome. Two atrophied
      abdominal testes were removed laparoscopically, 3 patients underwent a two-stage
      Fowler-Stephens procedure, and 28 underwent one-stage, laparoscopically assisted
      orchidopexy. An algorithm for surgical management of the impalpable testis based
      on laparoscopic findings is proposed.

PMID- 9244132
TI  - Additional considerations for inhaled nitric oxide therapy in congenital
      diaphragmatic hernia.

PMID- 9244133
TI  - Expanding the spectrum of ureteropelvic junction obstruction in duplex systems.

PMID- 9244134
TI  - An unusual case of testicular ectopia.

PMID- 9244135
TI  - Graduate education in the pharmaceutical sciences: how can it better meet the
      needs of the generic pharmaceutical industry?

PMID- 9244136
TI  - How does the NIGMS support program project grants? Where is current information
      available about this mechanism?

PMID- 9244137
TI  - Tissue engineering: a new field and its challenges.

PMID- 9244138
TI  - Gastrointestinal drug absorption: is it time to consider heterogeneity as well as
      homogeneity?
AB  - The current analysis of gastrointestinal absorption phenomena relies on the
      concept of homogeneity. However, drug dissolution, transit and uptake in the
      gastrointestinal tract are heterogeneous processes since they take place at
      interfaces of different phases under variable stirring conditions. Recent
      advances in physics and chemistry demonstrate that the geometry of the
      environment is of major importance for the treatment of heterogeneous processes.
      In this context, the heterogeneous character of in vivo drug dissolution, transit
      and uptake is discussed in terms of fractal concepts. Based on this analysis,
      drugs are classified in accordance with their gastrointestinal absorption
      characteristics into two broad categories i.e. homogeneous and heterogeneous. The
      former category includes drugs with satisfactory solubility and permeability
      which ensure the validity of the homogeneous hypothesis. Drugs with low
      solubility and permeability are termed heterogeneous since they traverse the
      entire gastrointestinal tract and therefore are more likely to exhibit
      heterogeneous dissolution, transit and uptake. The high variability of whole
      bowel transit and the unpredictability of conventional dissolution tests for
      heterogeneous drugs are interpreted on the basis of the fractal nature of these
      processes under in vivo conditions. The implications associated with the use of
      strict statistical criteria in bioequivalence studies for heterogeneous drugs are
      also pointed out.

PMID- 9244139
TI  - Scale-up of adhesive transdermal drug delivery systems.

PMID- 9244140
TI  - Cationic lipid-based gene delivery systems: pharmaceutical perspectives.
AB  - Gene delivery systems are designed to control the location of administered
      therapeutic genes within a patient's body. Successful in vivo gene transfer may
      require (i) the condensation of plasmid and its protection from nuclease
      degradation, (ii) cellular interaction and internalization of condensed plasmid,
      (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv)
      plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic
      protein can be, for instance, complexed with cationic liposomes or micelles in
      order to achieve effective in vivo gene transfer. A thorough knowledge of
      pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular
      biology is required to design optimal systems for gene therapy. This mini-review
      provides a critical discussion on cationic lipid-based gene delivery systems and
      their possible uses as pharmaceuticals.

PMID- 9244141
TI  - Modeling in frequency domain used for assessment of in vivo dissolution profile.
AB  - PURPOSE: To present a model-dependent approach for the assessment of the in vivo
      drug dissolution profile based on in vitro data for the multiple unit dosage
      form, as an alternative to the numerical method proposed in the study by Hayashi
      et al., Pharm Res. 12:1333-1337 (1995). METHODS: The data for aspirin granules
      administered to healthy subjects obtained in the above mentioned study were re
      evaluated. The subject dissolution system was considered to consist of two
      subsystems connected in series, i.e. the subsystem describing the gastric
      emptying process and the subsystem describing the intestinal dissolution process.
      The frequency response method was used to model the subject dissolution system.
      RESULTS: The model in vivo dissolution profile of aspirin, assessed as the
      integral of the model weighting function of the subject dissolution system, was
      in agreement with the in vivo cumulative absorption profile calculated by the
      Wagner-Nelson method. CONCLUSIONS: Comparison of dynamic properties of the
      subject dissolution system with the subsystem describing the gastric-emptying
      process yielded quantitative confirmation of the decisive role of the gastric
      emptying process in the in vivo drug dissolution after administration in the
      multi unit dosage form.

PMID- 9244142
TI  - Microdialysis studies of the distribution of stavudine into the central nervous
      system in the freely-moving rat.
AB  - PURPOSE: To study the extent and time course of distribution of stavudine (d4T)
      into the central nervous system (CNS) and to investigate the transport mechanisms
      of antiviral nucleosides in the CNS. METHODS: Microdialysis with on-line HPLC
      analysis was used to measure drug concentrations in the brain extracellular fluid
      (ECF) and cerebrospinal fluid (CSF) in the freely-moving rat. The in vivo
      recovery of d4T and zidovudine (AZT) was estimated by retrodialysis, which was
      validated by the zero-net flux method. The CNS distribution of d4T was
      investigated during iv and intracerebroventricular (icv) infusion. In the
      subsequent studies, the effect of AZT on CNS distribution of d4T was examined.
      RESULTS: During iv infusion, d4T distributed rapidly into the CNS. Its brain
      ECF/plasma and CSF/plasma steady-state concentration ratios were 0.33 +/- 0.06
      and 0.49 +/- 0.12, respectively (n = 15). During icv infusion, the steady-state
      d4T concentrations in the brain ECF were 23-fold higher than those during iv
      infusion, whereas its steady-state plasma levels were about the same for these
      two routes. Coadministration of AZT with d4T did not alter their respective brain
      distribution and systemic clearance at the concentrations examined. More
      importantly, the steady-state brain ECF/plasma and CSF/plasma concentration
      ratios of d4T were about 2-fold higher than those of AZT (0.15 +/- 0.04 and 0.25
      +/- 0.08) determined in the same animals. CONCLUSIONS: d4T readily crosses the
      blood-brain barrier (BBB) and blood-CSF barrier. An active efflux transport
      system in the BBB and blood-CSF barrier may be involved in transporting d4T out
      of the CNS. Direct icv administration of d4T can be used to enhance its brain
      delivery. Moreover, d4T exhibits a more favorable penetration into the CNS than
      AZT and therefore may be useful in the treatment of AIDS dementia complex.

PMID- 9244143
TI  - The disposition of valproyl glycinamide and valproyl glycine in rats.
AB  - PURPOSE: To investigate the disposition of valproyl glycinamide and valproyl
      glycine in rats and to compare it with that of valproic acid (VPA) and valpromide
      which were studied previously. METHODS: The study was carried out by monitoring
      the brain and liver levels of valproyl glycinamide and valproyl glycine (as a
      function of time after iv dosing) in addition to the regular pharmacokinetic (PK)
      monitoring of plasma and urine levels of these compounds. RESULTS: The following
      PK parameters were obtained for valproyl glycinamide and valproyl glycine,
      respectively: clearance, 7.1 and 16 ml/ min/kg; volume of distribution (Vss),
      0.78 and 0.41 l/kg; half-life, 1.1 and 0.37 h; and mean residence time, 1.8 and
      0.4 h. The ratios of AUCs of valproyl glycinamide of liver to plasma and brain to
      plasma were 0.70 and 0.66, respectively. The ratios of the AUCs of valproyl
      glycine of liver to plasma and brain to plasma were 0.19 and 0.02, respectively.
      CONCLUSIONS: Valproyl glycinamide distributes better in the brain than VPA, a
      fact which may contribute to its better anticonvulsant activity. Valproyl glycine
      was barely distributed in the brain, a fact which may explain its lack of
      anticonvulsant activity. In addition to the liver, the brain was found to be a
      minor metabolic site of the biotransformation of valproyl glycinamide to valproyl
      glycine.

PMID- 9244144
TI  - Tyramine-containing poly(4-nitrophenylacrylate) as iodinatable ligand carrier in
      biodistribution analysis.
AB  - PURPOSE: Targeted label or drug delivery requires access to convenient carrier
      systems and methods for efficient ligand conjugation. The main purpose of this
      study is to design an iodinatable synthetic polymer, whose application in vivo in
      tumor-bearing mice is tested with several related carbohydrate ligands, namely
      ABH and Lewis blood group epitopes. METHODS: Tyramine and aminopropyl derivatives
      of the synthetic oligosaccharides were attached to poly(4-nitrophenylacrylate).
      Following iodination, the biodistribution of the sugar-free and the substituted
      polymers was determined in tumor-bearing mice. Flow cytofluorimetric analysis
      assessed tumor cell binding of further ligand types to human tumor cells in
      vitro. RESULTS: Quantitative ligand incorporation was achieved under mild
      conditions. Whereas the ligand-free poly[N-(2-hydroxyethyl)acrylamide] (MW 30
      kDa) showed preferential accumulation in kidney, neoglycopolymers were found in
      substantial amounts in liver, kidney or spleen. The nature of the carbohydrate
      structure quantitatively influenced the distribution pattern. Tumor cell binding
      of blood group determinants and three further ligand types revealed non-uniform
      intensity in labeling and percentage of positive cells even in comparison between
      lines with identical histogenetic origin. CONCLUSIONS: Carbohydrate-exposing
      poly[N-(2-hydroxyethyl)acrylamide] polymers with tyramine as an iodine acceptor
      distribute in mice with a profile which is quantitatively influenced by small
      structural variations of the ligand part. Further refinement of the ligand
      structure may increase the level of selectivity for organ and tumor accumulation.

PMID- 9244145
TI  - Improved activity of a new angiotensin receptor antagonist by an injectable spray
      dried polymer microsphere preparation.
AB  - PURPOSE: To characterize and evaluate in vitro and in vivo the release mechanisms
      involved in spray-dried biodegradable microspheres having different Poly(D,L
      lactide) blend formulations and containing an antihypertensive drug (L-158,809).
      METHODS: Microspheres and blended polymers were characterized by DSC, SEM,
      confocal laser microscopy and size analysis. In vitro release studies were
      evaluated by using microspheres made from various blends of high and low
      molecular weight polymer. In vivo studies were evaluated by L-158,809 antagonist
      AT1 function versus the shift of the normal dose-response curve of blood pressure
      induced by Angiotensine II. RESULTS: The average yield of L-158,809 microspheres
      (10% (w/w)) was 95% of the theoretical loading. The average diameter of the
      microspheres was from 1 to 3 micrometers. In all release experiments, a
      significant burst effect (< 15%) was observed followed by a near zero-order
      release kinetics. In vivo studies with two different formulations show a strong
      shift of angiotensin II dose-response curve. CONCLUSIONS: The release kinetics
      and photomicrographs suggest that the system is best described as a multi
      parameter controlled released system in which the drug is molecularly dispersed.
      In vivo results demonstrating the controlled release of L-158,809.

PMID- 9244146
TI  - Development of freeze-dried albumin-free formulation of recombinant factor VIII
      SQ.
AB  - PURPOSE: To develop a stable freeze-dried formulation of recombinant factor VIII
      SQ (r-VIII SQ) without the addition of albumin. METHODS: Different formulations
      were evaluated for their protective effect during sterile filtration, freeze
      thawing, freeze-drying, reconstitution and long term storage. Factor VIII
      activity (VIII:C), visual inspection, clarity, solubility, moisture content and
      soluble aggregates and/ or fragments were assayed. RESULTS: A combination of non
      crystallising excipients (L-histidine and sucrose), a non-ionic surfactant
      (polysorbate 80) and a crystalline bulking agent (sodium chloride) was found to
      preserve the factor VIII activity during formulation, freeze-drying and storage.
      Calcium chloride was included to prevent dissociation of the heavy and light
      chains of r-VIII SQ. Sodium chloride was chosen as the primary bulking agent
      since the concentration of sodium chloride necessary for dissolution of r-VIII SQ
      in the buffer will inhibit the crystallization of many potential cake formers. It
      was found that L-histidine, besides functioning as a buffer, also protected r
      VIII SQ during freeze-drying and storage. A pH close to 7 was found to be
      optimal. Some potential macromolecular stabilisers, PEG 4000, Haes-steril and
      Haemaccel, were evaluated but they did not improve the recovery of VIII:C. The
      freeze-dried formulation was stable for at least two years at 7 degrees C and for
      at least one year at 25 degrees C. The reconstituted solution was stable for at
      least 100 hours at 25 degrees C. CONCLUSIONS: The albumin-free formulation
      resulted in consistently high recovery of VIII:C, very low aggregate formation
      and good storage stability. The stability of the reconstituted solution makes the
      formulation suitable for continuous administration via infusion pump. The
      formulation strategy described here may also be useful for other proteins which
      require a high ionic strength.

PMID- 9244147
TI  - A kinetic study on crystallization of an amorphous lubricant.
AB  - PURPOSE: The purpose of the work was to study the crystallization kinetics of
      amorphous sterotex K at different temperatures and with different methods, and to
      compare the obtained kinetic and thermodynamic results. METHODS: Isothermal
      microcalorimetry was the principal technique to determine the crystallization
      behavior of sterotex K. X-ray powder diffraction and differential scanning
      calorimetry were employed to interpret the microcalorimetric heat flow curves and
      compare the kinetics and the calculated value for the transition enthalpy.
      RESULTS: The best way to analyze the x-ray diffractograms was the statistic
      Wakelin's correlation method. The method gave consistent quantitative results
      with microcalorimetry and both methods showed crystallization to consist of two
      partially parallel part-processes, which attached probably to the different
      growing rates of the forms consisting of different lattice planes having the same
      spacing. The quantitative analysis of differential scanning calorimetry scans was
      troublesome to perform but the obtained average value of -51 J/g for the enthalpy
      of the crystallization was in good agreement with the values obtained with the
      other methods, the average being -52 J/g. Calculating heat flow versus released
      energy plots from the microcalorimetric data the crystallization mechanism was
      observed to change as a function of temperature. CONCLUSIONS: A sensitive
      isothermal microcalorimeter can give precise and fast knowledge about possible
      solid state transition mechanism, but the source of the heat flow signal must be
      verified with other analytical methods to avoid incorrect conclusions. Due to the
      sensitivity and the real-time data the microcalorimetry can show up the mechanism
      of the transition for varying as a function of temperature and reveal the
      uselessness of the conventional Arrhenius relationship for extrapolations.

PMID- 9244148
TI  - Determination of plasma protein adsorption on magnetic iron oxides: sample
      preparation.
AB  - PURPOSE: The purpose of this study was to investigate the influence of the sample
      preparation on the plasma protein adsorption pattern of polysaccharide-stabilized
      iron oxide particles by two-dimensional polyacrylamide gel electrophoresis (2-D
      PAGE). METHODS: The iron oxide particles were incubated in vitro in human plasma
      for five minutes. Thereafter, four different methods for particle recovery,
      including adsorbed proteins from surplus plasma, were investigated:
      centrifugation, magnetic separation, gel filtration and membrane-based static
      microfiltration. Adsorbed proteins were desorbed from the particle surfaces by
      surfactants and analyzed by 2-D PAGE, as described elsewhere (1,2). RESULTS: All
      the techniques investigated were able to separate small-size iron oxides (approx.
      110 nm) and adsorbed proteins from excess plasma. The gels obtained by the
      different separation procedures displayed almost identical adsorption patterns.
      Major proteins identified were: fibrinogen, IgG, albumin and an unclassified
      protein of about 70 kDa with a pI value of 6.5-7.5. CONCLUSIONS: Centrifugation
      was regarded as the most suitable separation method due to its speed and ease of
      use. In contrast to gel filtration, any washing media can be used. The magnetic
      separation process is restricted to particles with high inducible magnetic
      saturation, in particular, to iron oxides with overall sizes > 50 nm.

PMID- 9244150
TI  - Novel bioadhesive chitosan-EDTA conjugate protects leucine enkephalin from
      degradation by aminopeptidase N.
AB  - PURPOSE: To develop a novel bioadhesive polymer that protects peptide drugs from
      luminal degradation by aminopeptidase N and to evaluate the system in vitro on
      porcine mucosa. METHODS: EDTA was covalently bound to chitosan in order to
      combine the bioadhesive properties of the polymer with the well known capacity of
      EDTA to complexed metal ions which are essential for the enzymatic activity of
      proteases. The inhibitory effect of this polymer conjugate was evaluated by using
      leucine enkephalin (Leu enkephalin) as a model drug. The degree of Leu enkephalin
      degradation caused by aminopeptidase N (EC 3.4.11.2), as well as porcine mucosa,
      in the presence of the polymer conjugate, was quantified by HPLC analysis.
      RESULTS: The chitosan-EDTA conjugate is capable of binding 2.01 +/- 0.12 mmole of
      zinc per gram of polymer at pH 6.5 (n = 3; +/-S.D.). As zinc is an essential co
      factor for aminopeptidase N, enzyme activity (48 mU/ml) could be completely
      inhibited under the use of 1.0% chitosan-EDTA conjugate. The inhibitory effect of
      1.0% chitosan-EDTA conjugate on the degradation of Leu enkephalin on porcine
      mucosa within 3 h at 37 degrees C was even 2.9-fold higher than that of a
      recently developed zinc complexing bacitracin-poly(acrylic acid) conjugate of the
      same concentration. The novel polymer conjugate is more bioadhesive than
      unmodified chitosan and is easily hydratable in water and basic aqueous solutions
      exhibiting quick swelling properties. CONCLUSIONS: The bioadhesive polymer
      conjugate described here seems to be a useful tool in overcoming enzymatic
      degradation by aminopeptidase N.

PMID- 9244149
TI  - Assessment of dose proportionality, absolute bioavailability, and immunogenicity
      response of CTLA4Ig (BMS-188667), a novel immunosuppressive agent, following
      subcutaneous and intravenous administration to rats.
AB  - PURPOSE: The objectives of this study were: to delineate the pharmacokinetics of
      CTLA4Ig in rats after single and multiple intravenous (IV) and subcutaneous (SC)
      doses; to assess the relationship of the pharmacokinetic parameters of CTLA4Ig vs
      dose; to calculate the SC absolute bioavailability; and to assess the antibody
      response of CTLA4Ig. METHODS: A total of 48 (24 male and 24 female) Sprague
      Dawley rats were divided into eight treatments with 3 rats per gender in each
      group: a single dose of 10, 80, or 200 mg/kg of CTLA4Ig given either IV or SC and
      a repeated dose of 10 mg/kg (once every other day for 7 doses over 13 days) given
      either SC or IV. Serial blood samples were collected up to 43 days after single
      dose administration and up to 50 days following the administration of the last
      multiple dose on day 13. The serum concentration of CTLA4Ig and anti-CTLA4Ig
      antibodies were measured using ELISA assays. RESULTS: After single IV doses, Cmax
      and AUCinf increased in a dose proportional manner; CL appeared to be dose
      independent, while both Vss and T1/2 increased as the administered dose
      increased. Following single SC doses, Cmax and AUCinf increased in a linear
      manner but not proportionally; mean Tmax values were prolonged but similar among
      the three dose levels, while T1/2 increased as the administered dose increased.
      The absolute SC bioavailability of CTLA4Ig decreased as the dose increased from
      10 (62.5%), 80 (55.7%), and 200 mg/kg (41.1%). Comparison of the AUCtau values
      between the first and last doses suggested an accumulation (3.1-4.7) of CTLA4Ig.
      However, regardless of the route of dosing, AUCtau after the last dose were
      comparable to AUCinf values following the single dose. Anti-CTLA4Ig antibodies
      were detected at the 10 mg/kg dose level after single or multiple doses for both
      routes of administration. However, regardless of single or multiple doses,
      antibody titers were relatively greater for the SC compared to the IV
      administration. CONCLUSIONS: The key findings of this study were: (i) the
      elimination characteristics of CTLA4Ig were comparable between the SC and IV
      routes; (ii) the repeated dosing did not alter the pharmacokinetics of CTLA4Ig;
      (iii) the SC absolute bioavailability tended to decrease as the administered dose
      increased; and (iv) a greater formation of anti-CTLA4Ig antibodies was observed
      after SC compared to IV at a single 10 mg/kg dose level; however, after multiple
      dosing, the formation of antibodies from either of the two routes was relatively
      slower, and (v) during the study period, no antibodies were observed at either
      the 80 or 200 mg/kg dose levels regardless of the route of administration.

PMID- 9244151
TI  - Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of
      absorption enhancement.
AB  - PURPOSE: It has recently been shown that the absorption enhancing and toxic
      effects of chitosans are dependent on their chemical composition. In this study,
      the mechanisms underlying these effects were investigated at the cellular level.
      METHODS: The effects on epithelial cells of chitosans with different chemical
      composition, absorption enhancing properties and toxicities were studied in Caco
      2 monolayers. Chitosan C( 1:31) has a low degree of acetylation (DA) (1%) and a
      low m.w. (31 kD), and displays dose-dependent absorption enhancement and
      cytotoxicity; chitosan C(35:170) has a higher DA (35%) and a higher m.w. (170
      kD), is less dose-dependent in absorption enhancement, and is not cytotoxic. A
      third non-toxic chitosan C(49:22) with a high DA (49%), a low m.w. (22 kD), and
      no influence on epithelial permeability was used as control. RESULTS: C(1:31) and
      C(35:170) bound tightly to the epithelium. Cellular uptake of the chitosans was
      not observed. Both chitosans increased apical but not basolateral cell membrane
      permeability and induced a redistribution of cytoskeletal F-actin and the tight
      junction protein ZO-1. This resulted in increased paracellular permeability of
      hydrophilic marker molecules of different molecular weights. Addition of
      negatively charged heparin inhibited the cellular and the absorption enhancing
      effects of the chitosans, indicating that these effects are mediated via their
      positive charges. The onset of the effects of C(35:170) on apical membrane
      permeability and tight junction structure was much faster than that of C(1:31).
      C(49:22) did not influence any of the properties of the Caco-2 cell monolayers
      studied. CONCLUSIONS: The binding and absorption enhancing effects of chitosans
      on epithelial cells are mediated through their positive charges. The interaction
      of chitosans with the cell membrane results in a structural reorganisation of
      tight junction-associated proteins which is followed by enhanced transport
      through the paracellular pathway.

PMID- 9244152
TI  - Mechanism of absorption enhancement in humans after rectal administration of
      ampicillin in suppositories containing sodium caprate.
AB  - PURPOSE: The medium chain fatty acid sodium caprate (C10) is approved as an
      absorption enhancer but its mechanism of action has not been studied in humans.
      The aim of this study was to investigate the mechanism of action of C10 in human
      subjects after rectal administration. METHODS: Twelve healthy human subjects were
      randomised to receive ampicillin suppositories with (AM-C10) or without (AM) C10.
      Serum and urine samples were collected and analysed for ampicillin by HPLC.
      Rectal biopsies were taken before and 25 min (approximate time of maximum serum
      concentration, Cmax, for ampicillin) and 185 min (during the final part of the
      elimination phase) after rectal administration of the suppositories. The
      osmolality of the rectal fluid was also measured. RESULTS: AM-C10 administration
      increased Cmax, area under the serum concentration-time curve (AUC) and urinary
      recovery of ampicillin 2.6-, 2.3- and 1.8-fold, respectively, compared to AM.
      Histological examination of the biopsies showed that AM-C10 exposure resulted in
      reversible mucosal damage that occurred at the same time as the Cmax for
      ampicillin while AM prolonged mucosal damage. A reversible increase in rectal
      fluid osmolality was observed with both treatments. CONCLUSIONS: AM-C10-enhanced
      absorption of ampicillin coincides with non-specific damage to the rectal mucosa.
      C10 itself as well as the suppository base and the hyperosmolality of the rectal
      fluid contributed to this effect. However, the histological damage was reversible
      with AM-C10, suggesting that C10 also has a protective effect on the rectal
      mucosa.

PMID- 9244154
TI  - A novel in vitro electrophysiological bioassay for transport of loperamide across
      intestinal epithelia.

PMID- 9244153
TI  - Characterization of guanidine transport in human renal brush border membranes.
AB  - PURPOSE: Organic cation transporters in the renal proximal tubule are important
      in the secretion of many clinically used drugs and their metabolites. The goal of
      this study was to determine the mechanisms of guanidine transport in human
      kidney. METHODS: Brush-border membrane vesicles were prepared from donor human
      kidneys deemed unsuitable for renal transplantation. RESULTS: Uptake of [14C]
      guanidine (50 microM) in the vesicles, as determined by rapid filtration, was
      significantly greater in the presence of an outwardly-directed proton gradient,
      at all early time points, than in the absence of the gradient. Proton-stimulated
      uptake of [14C]-guanidine at 30 sec (32.0 +/- 1.24 pmol/mg protein) was
      significantly inhibited by a number of organic cations including 5 mM unlabeled
      guanidine (14.8 +/- 1.84 pmol/mg protein) and 5 mM MIBA (9.14 +/- 3.80 pmol/ mg
      protein), but not by 5 mM TEA (28.4 +/- 5.67 pmol/mg protein). Guanidine, but not
      TEA, trans-stimulated [14C]-guanidine uptake. Conversely, TEA, but not guanidine,
      trans-stimulated [14C]-TEA uptake in the vesicles. The proton-dependent transport
      of guanidine was characterized by a Km of 3.52 +/- 0.42 mM (SE) and a Vmax of
      34.6 +/- 8.64 pmol/mg protein/sec (SE). CONCLUSIONS: These results demonstrate
      that guanidine transport in human renal brush border membrane vesicles is
      stimulated by a proton gradient. Evidence was obtained suggesting that the
      transporter for guanidine is distinct from the previously described organic
      cation proton antiporter for TEA.

PMID- 9244155
TI  - Direct determination of drug content in semisolid formulations using step-scan FT
      IR photoacoustic spectroscopy.

PMID- 9244156
TI  - Application of moment analysis to the sigmoid effect model for drug administered
      intravenously.

PMID- 9244157
TI  - Neurally mediated syncope: a review of cardiac and arterial receptors.
AB  - This article reviews the basic physiology of the reflexogenic areas of the heart
      and the mechano- and baroreceptors that regulate cardiovascular and autonomic
      homeostasis, all of which contribute to our understanding of the pathogenesis of
      neurally mediated syncope. The mechanisms of neurally mediated syncope may
      involve excessive activation of ventricular receptors that trigger severe
      hypotension and bradycardia. Thus, neurally mediated syncope may be the clinical
      expression of the Bezold-Jarisch reflex, which occurs in situations of increased
      sympathetic activity, perhaps as a result of heightened cardiac receptor
      sensitivity. The arterial baroreceptors exert a ubiquitous influence on the heart
      and circulation, and serve primarily to buffer transient changes in arterial
      pressure by transmitting sensory information regarding their stretch to the
      central nervous system. This information, in conjunction with cardiac receptor
      input, elicits alterations in neural efferent output from sympathetic and
      parasympathetic fibers to provide subtle, continuous regulation of beat-to-beat
      cardiovascular hemodynamics to an array of physiologic and psychological
      stressors.

PMID- 9244158
TI  - Neurally mediated syncope and syncope due to autonomic failure: differences and
      similarities.
AB  - Syncope is a transient loss of consciousness and postural tone caused by a global
      reduction of blood flow to the brain. Abnormalities in autonomic cardiovascular
      control can impair blood supply to the brain and produce syncope in two different
      disorders: autonomic failure and neurally mediated syncope. In autonomic failure,
      sympathetic efferent activity is chronically impaired so that vasoconstriction is
      deficient, upon standing blood pressure always falls (i.e., orthostatic
      hypotension), and syncope or presyncope occurs. Conversely, in neurally mediated
      syncope, the failure of sympathetic efferent vasoconstrictor traffic (and
      hypotension) occurs episodically and in response to a trigger. Between syncopal
      episodes, patients with neurally mediated syncope have normal blood pressure and
      orthostatic tolerance. This article reviews the characteristics of autonomic
      failure and describes in more detail the pathophysiology, diagnosis, and
      treatment of neurally mediated syncope.

PMID- 9244159
TI  - Electroencephalography in syncope.
AB  - Electroencephalographic (EEG) findings in syncope are reviewed. There are four
      major categories of syncope: neurally mediated (neurocardiogenic), neurologic,
      decreased cardiac output, and orthostatic hypotension. However, regardless of
      cause, whether the syncope is due to a vasovagal effect, a cardiac arrhythmia, an
      epileptic seizure, or hypotension, EEG findings are similar and reflect cerebral
      hypoperfusion. Initially there may be a slowing of background rhythms. This is
      followed by high amplitude delta activity, maximal anteriorly. If the
      hypoperfusion persists there is subsequent flattening of the EEG. The EEG returns
      to normal in the reverse sequence. In cases with severe and prolonged ischemia,
      convulsive syncope may occur at the time of the EEG flattening. Although not an
      epileptic phenomena, clinically this is often mistaken for epilepsy. Conversely,
      epileptic disorders, such as the ictal bradycardia syndrome, may occasionally
      mimic syncope. Therefore, in patients in whom EEGs are performed for the
      evaluation of an episode of loss of consciousness, simultaneous ECG should be
      used.

PMID- 9244160
TI  - Comparison between visual scoring of cyclic alternating pattern (CAP) and
      computerized assessment of slow EEG oscillations in the transition from light to
      deep non-REM sleep.
AB  - Ten healthy volunteers (six men and four women) aged between 20 and 30 years
      underwent a nocturnal polygraphic recording on paper and on tape. Spectral
      analysis was accomplished and EEG sleep scored according to standard criteria and
      to the guidelines for the identification of cyclic alternating pattern (CAP). The
      initial 25 min of sleep, starting from the first clear-cut k-complex and ending
      within stage 4, was subdivided into five consecutive blocks of 5 min each. Using
      a zero-crossing technique, we evaluated the number of total power oscillations in
      each block and we tested the hypothesis of significant modifications of the
      number of total power oscillations and of their periodicity in the successive
      sessions. In addition, we measured the gap between the maximum and minimum
      values, respectively, of two successive half-waves making up each oscillation.
      The hypothesis of time-related trends of the values of the gaps was tested by
      means of linear regression techniques. Within the 25-min time span, the number of
      periodic oscillations and the number of CAP cycles showed significant increases.
      The amplitude gaps underwent a decreasing trend. The present data suggest that
      slow rhythmic oscillations expressed by CAP can be detected by means of spectral
      analysis. Their dynamics suggests a close relationship with the EEG
      synchronization processes.

PMID- 9244161
TI  - Amplitude changes of tibial nerve cortical somatosensory evoked potentials when
      the ipsilateral or contralateral ear is used as reference.
AB  - We performed topographical mapping of somatosensory evoked potentials (SEPs) to
      the posterior tibial nerve using earlobe references both ipsilateral and
      contralateral to the stimulation side. The voltage of the frontal contralateral
      N37 and P50 components was enhanced, while the voltage of the parietal
      ipsilateral P37 and N50 components was reduced when the contralateral earlobe was
      substituted by the ipsilateral earlobe reference. Maps of the same data
      documented concomitant changes in negative and positive potential fields, showing
      an expansion of the pre-Rolandic N37 toward the centrotemporal contralateral
      regions, and a tendency of the parietal ipsilateral P37, N50 components to be
      more focally distributed at the vertex. SEPs recorded at each earlobe (Cv6
      reference) provided an explanation of these results: The contralateral earlobe
      detected a negative potential corresponding to the N37 potential recorded over
      the scalp, followed by a P50 potential that attenuated the contralateral
      responses and enhanced the ipsilateral ones. The ipsilateral earlobe had no
      significant effects on scalp SEPs, since it detected only a large N33 negativity.
      Current source density (CSD) maps were, of course, not influenced by the ear used
      as reference. Our results suggest that the ipsilateral ear reference is better
      than the contralateral one for recording "genuine" cortical SEPs. Therefore, it
      can be recommended in the clinical domain for mapping studies of lower-limb
      cortical SEPs.

PMID- 9244162
TI  - Speech and the dominant superior frontal gyrus: correlation of ictal symptoms,
      EEG, and results of surgical resection.
AB  - Two patients with seizures characterized by speech arrest had astrocytoma in the
      superior frontal gyrus (SFG) of the left hemisphere. Preoperative video EEG
      monitoring of seizures using subdural electrode arrays showed that comprehension,
      crude vocalization, and limb and tongue movements were preserved during speech
      arrest. One patient had difficulty writing during seizures. Ictal EEG onset was
      localized to the SFG without involvement of Broca's area. Electrical stimulation
      of SFG electrodes reproduced the speech arrest and writing difficulty. Resection
      of this region reduced seizures but did not result in lasting speech deficit.
      Cessation of speech with electrical stimulation of the superior frontal gyrus
      occurs by interrupting control of muscles required for speaking, which occurs
      independently of simple 'negative' motor effects. We postulate that functional
      redundancy is the basis for resection of this region without producing
      significant speech deficits.

PMID- 9244163
TI  - Epileptiform abnormalities in hepatic encephalopathy.
AB  - Epileptiform abnormalities are uncommon in patients with hepatic encephalopathy.
      A review of EEGs in patients with hepatic encephalopathy over a 10-year period
      identified 18 (15%) with epileptiform abnormalities. Thirteen patients had
      interictal discharges consisting of focal spike and sharp wave discharges,
      bilateral independent discharges, and generalized spike and wave discharges. A
      total of 10 patients had electrographic seizure discharges, focal in 6 and
      generalized in 5 (some patients had more than one abnormality). Twelve patients
      had clinical seizures, partial in four and generalized in eight. Neuroimaging
      failed to provide an etiology for the generation of epileptiform discharges in
      most patients, including those with focal abnormalities. Most patients with
      epileptiform discharges died or deteriorated. We conclude that epileptiform can
      be seen in patients with hepatic encephalopathy, and when present imply a poor
      prognosis.

PMID- 9244164
TI  - Repetitive phrenic nerve stimulation study in normal subjects.
AB  - In patients with myasthenia gravis (MG), it may be difficult to determine by
      clinical methods if respiratory insufficiency is due to a defect in neuromuscular
      transmission. We therefore studied the technique of repetitive electrical
      stimulation of the phrenic nerve in 6 healthy subjects. It was easily performed
      and quite reproducible. Responses at 3-Hz stimulation were recorded from surface
      electrodes of the ipsilateral hemidiaphragm, before and after exercise. We
      analyzed the percent decrement of the negative peak (NP) amplitude, area, and
      duration of the diaphragmatic compound muscle action potential (CMAP) between the
      first and the fifth or sixth potentials. The mean percentage change of the area
      was -2.2% (+/-4.3), and in all tests the change was <10.6%, yielding a normal
      range of <11%. The change in the NP amplitude was 12.1% (+/-8.3); in duration,
      the change was -8.7% (+/-9.6). Producing diaphragm fatigue did not change these
      results. The increase in amplitude and decrease in duration with little change in
      area, termed pseudofacilitation, may be due to shifts in the position of the
      diaphragm affecting volume conduction. The technique is a promising tool in the
      diagnosis of respiratory involvement from neuromuscular transmission disorders.

PMID- 9244165
TI  - Evaluation of cerebral function after carotid endarterectomy.
AB  - Neuroimaging methods have failed to disclose correlation between degree of
      cerebral atrophy and blood flow in carotid artery stenosis patients. Moreover,
      intellectual improvement after carotid endarterectomy does not correlate fully
      with neuroimaging data in such patients. We performed brain electrical activity
      mapping and psychological testing before and 4 weeks after operation in 28
      patients with symptomatic, high-grade, carotid stenosis. Postoperatively,
      electroencephalographic (EEG) mean frequency and absolute theta power improved
      significantly (p < 0.01). Mean frequency increased >1 Hz in most areas while
      power decreased dramatically, mainly because of resolution of high-voltage foci
      in 8 patients. Differences were conspicuous in both frontal lobes irrespective of
      the operated side, which suggests changes in perfusion affecting the whole brain.
      This is a positive effect of endarterectomy. Mini-Mental test and Set Test for
      verbal fluency had a positive correlation with the qEEG changes. Quantitative EEG
      as a measure of cerebral function has disclosed discriminative improvement in the
      early postoperative period. Our results support the thesis of improvement
      subsequent to endarterectomy.

PMID- 9244166
TI  - Can epileptologists without access to intracranial EEG use reliably the
      International League Against Epilepsy classification of the localization-related
      epileptic syndromes? A stereo-electroencephalographic study.
AB  - The goal of the present study was to investigate the reliability of clinical and
      electroencephalographic (EEG) criteria for the classification of localization
      related epileptic syndromes as listed in the Proposals of Revised Classification
      of Epilepsies and Epileptic Syndromes 1989 (ICE). ICE distinguishes between
      multiple syndromes within epilepsies of a given lobe. Intracranial recordings
      were the main element in the development of the revised ICE. Considering that
      most epilepsy centers have no access to such invasive techniques for precise
      anatomic localization, it was of interest to assess how accurately the seizure
      origin could be determined from the scalp EEG and clinical data as reported in
      ICE. In this retrospective study, we compared the accuracy of the topographic
      diagnosis made by two groups of physicians evaluating the same patients-one group
      with and the other without access to results of stereo-EEG (SEEG). Medical files
      of 87 patients with intractable localization-related epilepsy were analyzed: 38
      with frontal, 37 with temporal, 10 with parietal, and 2 with occipital lobe
      epilepsy were included in the study. All patients underwent previous SEEG and
      successful cortectomy. Minimum follow-up was 5 years. In most cases, noninvasive
      techniques and criteria suggested by ICE allowed topographic diagnosis of focal
      epilepsies according to brain lobe involvement. More detailed diagnosis,
      localizing the origin of critical activity within a lobe, was often unreliable.
      Further data are required for a definition of the epileptogenic zone. A
      spatiotemporal evaluation of critical events, including the intracranial EEG
      recording, remains the best method for topographic diagnosis of localization
      related epilepsy.

PMID- 9244167
TI  - Polymorphonuclear leukocyte lysosomal proteases, cathepsins B and D affect the
      fibrinolytic system in human umbilical vein endothelial cells.
AB  - To clarify the physiological role played by neutrophil lysosomal protease in
      cultured human umbilical vein endothelial cells (HUVEC), we studied the effects
      of cathepsins B and D released from activated polymorphonuclear leukocytes on the
      fibrinolytic system in HUVEC. Cathepsins B and D reduced the antigens of tissue
      type plasminogen activator, and they increased both the antigens and the activity
      of plasminogen activator inhibitor-1. These results suggest that cathepsins B and
      D are involved in the thrombotic tendency, since they inhibited the fibrinolytic
      system in cultured HUVEC.

PMID- 9244168
TI  - Lipopolysaccharide decreases oxygen consumption by Mono Mac 6 cells; an electron
      paramagnetic resonance oximetry study.
AB  - The rate of oxygen consumption in the human acute monocytic leukemia-derived cell
      line, Mono Mac 6, in response to lipopolysaccharide (LPS) in vitro was measured
      by electron paramagnetic resonance spectroscopy using an oxygen-sensitive spin
      label, 4-oxo-2,2,6,6-tetramethylpiperidine-d16-1-oxyl (15N-PDT).
      Lipopolysaccharide impaired oxygen consumption in a dose-dependent manner which
      was shown to be mediated by mitochondrial dysfunction and could be augmented by
      pretreatment of the cells with interferon-gamma. Treatment of the cells with anti
      CD14 monoclonal antibody failed to inhibit the LPS-induced effects on cellular
      respiration. These results suggest that LPS can directly reduce normal cellular
      oxygen consumption possibly via a CD14-independent pathway. This alteration of
      mitochondrial function by LPS may be responsible for the observed cell damage
      during sepsis.

PMID- 9244169
TI  - IRS-I expression on the luteinized rat ovary: IGF-I and cyclic AMP effects on IRS
      I tyrosine phosphorylation.
AB  - The expression of insulin receptor substrate-I (IRS-I) mRNA was demonstrated in
      rat luteal cells by Northern blot analysis, in situ hybridization as well as by
      reverse transcriptase polymerase chain reaction. Western blot with a polyclonal
      anti IRS-I antibody showed the presence of a 183 kDa protein which corresponds to
      the size of IRS-I reported in other tissues. Further studies were performed to
      determine whether human chorionic gonadotropin (hCG) can interact with the
      insulin-like growth factor-I (IGF-I) signaling pathway to increase tyrosine
      phosphorylation of IRS-I. While hCG alone was ineffective in stimulating the
      phosphorylation of IRS-I, IGF-I mediated phosphorylation of IRS-I was increased
      by prior exposure to hCG. These results were further confirmed by the
      immunoprecipitation of IRS-I from the lysate of hCG- and IGF-I-treated luteal
      cell cultures followed by Western blotting with anti-phosphotyrosine antibody.
      Similarly, pretreatment with forskolin also increased IGF-I stimulated IRS-I
      phosphorylation. The increased tyrosine phosphorylation of IRS-I seen in response
      to IGF-I stimulation following treatment with either hCG or forskolin was not due
      to an increase in IRS-I content. Furthermore, IGF-I receptor tyrosine kinase
      activity was not affected by forskolin, suggesting that the increase in IRS-I
      tyrosine phosphorylation was not the result of an increase in its activity. Thus,
      we conclude that hCG/LH and IGF-I signaling pathways 'cross-talk' to increase the
      levels of IRS-I tyrosine phosphorylation. The observed increase in IRS-I tyrosine
      phosphorylation may be the result of an increase in the stability of the
      phosphorylated form of IRS-I.

PMID- 9244170
TI  - Effect of K+-induced depolarization on carbachol-stimulated inositol
      tetrakisphosphate accumulation in rat cerebrocortical slices.
AB  - Carbachol-stimulated accumulation of labeled IP4 or of total Ins 1,3,4,5-P4 in
      rat brain cortical slices was maximal in buffer containing 10 mM K+. Iso-osmotic
      elevation of extracellular K+ to 30 mM did not affect total Ins 1,3,4,5-P4
      accumulation but did enhance carbachol stimulated Ins 1,4,5-P3 accumulation. Iso
      osmotically elevated K+ suppressed carbachol stimulated accumulation of labeled
      IP4 while enhancing accumulation of labeled inositol mono-, bis- and
      trisphosphates. High K+ alone increased basal accumulation of labeled inositol
      mono-, bis- and trisphosphates, and total Ins 1,4,5-P3, while having no
      significant effect on accumulation of labeled IP4 or total Ins 1,3,4,5-P4. Long
      term incubation with hyper-osmotically elevated K+ potentiated carbachol
      stimulated Ins 1,3,4,5-P4 accumulation at 5 min. However, hyper-osmotically
      elevated K+ suppressed accumulation of labeled IP4 due to carbachol. These
      results indicate that there is no short-term effect of iso-osmotically elevated
      K+ on carbachol-stimulated total Ins 1,3,4,5-P4 accumulation. Furthermore,
      elevating K+ above 10 mM either iso-osmotically or hyper-osmotically suppresses
      carbachol stimulated accumulation of labeled IP4. The results suggest that the
      altered Na+/K+ ratio influenced the production of inositol tetrakisphosphates and
      emphasize the important role of cations such as Na+, K+, and Ca2+ in the receptor
      mediated inositol response. Moreover, the results underscore the unique ability
      of carbachol (a cholinergic agonist) to stimulate significant accumulation of
      inositol tetrakisphosphate.

PMID- 9244171
TI  - Isolation of pepsin-resistant laminin fragments from human placenta: effect on
      epithelial cells cultured from the kidneys of patients with autosomal dominant
      polycystic kidney disease (ADPKD).
AB  - Laminin isolated from human placenta was subjected to prolonged pepsin digestion.
      Seven peptide fragments (designated N1 to N7) were separated by ion-exchange
      chromatography and gel filtration and characterised by SDS-polyacrylamide gel
      electrophoresis and immunoblotting. The molecular size of the laminin fragments
      varied from approx. 900,000 (N1) to 28,000 (N7). Epithelial cells obtained from
      normal kidneys and patients with autosomal dominant polycystic kidney disease
      (ADPKD) were cultured. The incorporation of [3H]thymidine was measured over 96 h
      to determine the effect of the addition of the different fragments and whole
      laminin from EHS tumour to the cells. The rate of growth of both normal and
      polycystic cells was increased in the presence of the laminin fragments but this
      effect was more pronounced in the ADPKD cells.

PMID- 9244172
TI  - Serine isotopmer analysis by 13C-NMR defines glycine-serine interconversion in
      situ in the renal proximal tubule.
AB  - [2-(13)C]glycine metabolism was studied in freshly isolated rat renal proximal
      tubules. Mitochondrial coupling of the glycine cleavage complex (GC) and serine
      hydroxymethyltransferase (SHMT) was confirmed by the formation of three serine
      isotopomers, [2-(13)C]-, [3-(13)C]- and [2,3-(13)C]serine, detected by 13C-NMR.
      Incubation with different fractions of 13C-labelled glycine altered the labelling
      pattern of the serine isotopomers predictably and allowed calculation of the 13C
      labelled fractions of total glycine and methylene in N5,N10
      methylenetetrahydrofolate (m-THF) available for serine metabolism. Within 20 min
      there was a fall in labelled glycine (to 42 +/- 3, 68 +/- 3 and 93 +/- 2%, (n =
      4, mean +/- S.D.) from 50%, 75% and 100% 13C-labelled added glycine
      respectively), followed by a slow rate of endogenous glycine formation for up to
      80 min incubation. The C2 of glycine was the source of more than 90% of the
      methylene group of m-THF formed. Gas chromatography-mass spectroscopy (GC-MS)
      showed that greater than 50% of serine formed was unlabelled. GC and SHMT
      proceeded in the direction of serine formation. Serine isotopomer analysis by NMR
      and GC-MS allowed the actions of GC and SHMT and de novo contributions to
      glycine, serine and m-THF to be monitored in situ in fresh renal proximal
      tubules.

PMID- 9244173
TI  - Modulation of glycine-serine interconversion by TCA and glycolytic intermediates
      in normoxic and hypoxic proximal tubules.
AB  - Glycine-serine interconversion is important to numerous metabolic processes and
      serine release by the kidney. Incubation of freshly isolated rat renal proximal
      tubules with 5 mM glycine 75% 13C-labelled in the 2-position resulted in 13C
      labelled incorporation into serine of 69 micromol.g protein(-1) (+/- 14, n = 16)
      at 20 min. Addition of 5 mM glucose, 4 mM lactate, 1 mM alanine, 1 mM butyrate
      and 1 mM glutamate increased 13C-label incorporation into serine to 173
      micromol.g protein(-1) (+/- 32, n = 4) at 60 min, 50% greater than tubules
      incubated with 5 mM glycine alone (P < 0.05). The increase was prevented by
      hypoxia. Reoxygenation for 20 min restored the rate of incorporation of 13C-label
      into serine. The fraction of unlabelled serine remained approximately 47% at 20,
      40 and 60 min in each group. The results indicate that in the presence of oxygen,
      TCA and glycolytic intermediates stimulate serine synthesis via the glycine
      cleavage complex and serine hydroxymethyltransferase pathways and not the
      phosphorylated pathway. In addition, significant serine production occurs from an
      unidentified source, which is also tightly coupled to glycine metabolism. Both in
      the presence and absence of added TCA and glycolytic intermediates, glycine was
      the principle source of the methylene group in methylene tetrahydrofolate.

PMID- 9244174
TI  - Stimulation of prostaglandin E2 synthesis by interleukin-1beta is amplified by
      interferons but inhibited by interleukin-4 in human amnion-derived WISH cells.
AB  - Human amnion-derived WISH cells synthesize little prostaglandin E2 at the basal
      state. However, the cells were stimulated greatly to synthesize prostaglandin E2
      by interleukin-1beta in a dose-dependent manner. Stimulation by interleukin-1beta
      was synergistically increased by pretreatment of the cells with interferon alpha
      or gamma, which alone were inactive. Synergism by interferons was dose-dependent.
      Stimulation by interleukin-1beta, on the contrary, was inhibited by preincubation
      of the cells with interleukin-4. Inhibition by interleukin-4 was also dose
      dependent. Regulation of prostaglandin E2 synthesis by cytokines was further
      examined at the m-RNA level of cyclooxygenase-2. Quantitative reverse
      transcription-polymerase chain reaction indicated that the m-RNA level was not
      increased by interferon-gamma but was synergistically increased by interferon
      gamma plus interleukin-1beta. Furthermore, the m-RNA level increased by
      interleukin-1beta was attenuated by interleukin-4. These results indicate that
      regulation of interleukin-1beta-stimulated prostaglandin E2 synthesis by
      interferons and interleukin-4 is controlled at the m-RNA level of cyclooxygenase
      2.

PMID- 9244175
TI  - Retrovirus budding may constitute a port of entry for drug carriers.
AB  - This paper investigates the relation between viral infection and cell uptake of
      liposomes and nanoparticles. A defective virus was used to infect two types of
      cells: cells allowing virus budding (psi2neo cells) and cells bereft of a virus
      exit process (NIH 3T3 cells). This study has revealed that cell uptake of pH
      sensitive-liposomes is highly dependent on the virus exit process, since it
      ensued only when virus budding occurred. This preferential uptake of pH-sensitive
      liposomes by infected cells was not carrier-specific because similar uptake was
      observed with non-biodegradable fluorescent nanoparticles using confocal
      microscopy. Also, inhibition of neo gene expression by oligonucleotide pH
      sensitive-liposomes was only observed in the cell system (psi2neo) endowed with a
      virus exit process. Finally, increased membrane fluidity was noted in the
      infected cells, possibly reflecting membrane perturbation due to virus budding.
      We suggest that this membrane perturbation may be the key to the uptake of the
      different colloidal carriers. Infected cells could, thus, constitute a natural
      target for particulate drug carriers.

PMID- 9244176
TI  - Mastoparan elicits prostaglandin E2 generation and inhibits inositol phosphate
      accumulation via different mechanisms in rabbit astrocytes.
AB  - The effects of mastoparan on phosphoinositide hydrolysis and prostaglandin E2
      (PGE2) generation were investigated in astrocytes cultured from rabbit brain.
      Mastoparan inhibited the accumulations of [3H]inositol phosphates induced by
      bradykinin (1 microM) in a time- and concentration-dependent manner. Mastoparan
      (3-30 microM) also released PGE2 in a time- and concentration-dependent manner.
      Mastoparan-induced release of PGE2 was inhibited by indomethacin, a
      cyclooxygenase inhibitor, by dexamethasone, a steroidal anti-inflammatory drug,
      and by pertussis toxin, an inactivator of some G proteins, such as Gi and Go.
      Mastoparan also caused [3H]arachidonic acid liberation, which was inhibited by
      dexamethasone or pertussis toxin. In contrast, indomethacin, dexamethasone and
      pertussis toxin failed to attenuate mastoparan-induced inhibition of [3H]inositol
      phosphate accumulation induced by bradykinin. Thus, mastoparan-induced inhibition
      of phosphoinositide hydrolysis does not involve pertussis toxin-sensitive G
      protein nor arachidonic acid metabolites. In addition to the inhibition of
      phospholipase C, mastoparan activates phospholipase A2 through pertussis toxin
      sensitive G protein.

PMID- 9244177
TI  - Nuclear localization of a complex of fibroblast growth factor(FGF)-1 and an NH2
      terminal fragment of FGF receptor isoforms R4 and R1alpha in human liver cells.
AB  - FGF ligands and FGF receptor 1 (FGFR1) appear associated with the nucleus in
      addition to their extracellular and transmembrane locations. After receptor
      dependent internalization in liver cells, radiolabeled 16-kDa FGF-1 appears in a
      40-kDa covalent complex with a cellular protein. In this report, we show that in
      a human hepatoma cell line, HepG2, which expresses both FGFR4 and FGFR1, the 40
      kDa complex cross-reacts with antibodies against the ectodomain of both types of
      receptors. In addition to antibody against FGF-1, a polyclonal antiserum against
      the three immunoglobulin (Ig)-like loop ectodomain of FGFR4 and a monoclonal
      antibody to a 19-residue sequence in the NH2-terminus of the NH2-terminal Ig Loop
      I of the three loop splice variant of FGFR1 (FGFR1alpha) reacts with the complex.
      A monoclonal antibody against an epitope in FGFR1 downstream of the inter-loop
      I/II sequence which reacts with intact FGFR1 failed to cross-react with the 40
      kDa complex. Cell fractionations and indirect immunofluorescent localization
      revealed that the 40-kDa complex associates with the particulate fraction of
      cells, particularly the nucleus and associated cytoskeletal elements. We propose
      that the NH2-terminal Ig-loop of the three loop isoforms of FGFR, which are
      generally associated inversely with cell growth, may play a role at or in the
      nucleus in addition to modification of affinity of the FGFR ectodomain for
      heparan sulfate and FGF ligand.

PMID- 9244178
TI  - 15N-NMR study of ammonium assimilation in Agaricus bisporus.
AB  - Ammonium assimilation was studied by feeding [15N]ammonium to actively growing
      mycelium of Agaricus bisporus. Products of ammonium assimilation were analysed
      using 15N-NMR. Participation of glutamine synthetase, glutamate synthase and NADP
      dependent glutamate dehydrogenase was determined by inhibiting glutamine
      synthetase with phosphinothricin and glutamate synthase with azaserine. Our
      results clearly indicate that, under the conditions used, ammonium assimilation
      is mainly catalysed by the enzymes of the glutamine synthetase/glutamate synthase
      pathway. No indications were found for participation of NADP-dependent glutamate
      dehydrogenase. Furthermore, 15N-labelling shows that transamination of glutamate
      with pyruvate to yield alanine is a major route in nitrogen metabolism. Another
      major route is the formation of N-acetylglucosamine. Compared to the formation of
      N-acetylglucosamine there was only a limited formation of arginine.

PMID- 9244179
TI  - Characterisation and antiproliferative activity of an alpha-type murine
      interferon from embryonic fibroblasts.
AB  - Interferons play a part in the negative control of cell proliferation of
      mammalian cells. Here a natural interferon has been isolated from soluble
      proteins secreted by secondary murine embryonic fibroblasts using Blue Sepharose
      chromatography, immunoaffinity exclusion and Q Sepharose ion exchange
      fractionation. Partial amino acid sequencing assigns it to the interferon alpha
      family. Its biological and physico-chemical properties single it out from all
      other murine alpha interferons. The embryonic interferon has stronger
      antiproliferative activity, is acid labile, has stronger affinity for Blue
      Sepharose and weak affinity for antibodies which recognise other murine
      interferon alpha subtypes.

PMID- 9244180
TI  - Heparin-steroid conjugates lacking glucocorticoid or mineralocorticoid activities
      inhibit the proliferation of vascular endothelial cells.
AB  - A new class of angiogenesis inhibitors consist of a non-anticoagulating
      derivative of heparin, which binds to vascular endothelial cells, coupled to a
      steriod (e.g., cortisol) which suppresses endothelial cell division. We linked
      heparin to a further 10 steroids in an effort to identify ones which would yield
      more effective or safer angiogenesis inhibitors. Steroids having a C3 ketone
      group were linked by reaction with a hydrazide derivative of heparin. Steroids
      having a C20 ketone group and lacking a C3 ketone could not be prepared by this
      method, necessitating the development of alternative methods. The most efficient
      was to convert the steroid into a derivative having a hydrazone group at C20 and
      then link the steroid hydrazone to heparin. Conjugates prepared from steroids
      having C3 ketones were at most 6-fold more inhibitory than the free steroids to
      endothelial cells in tissue culture. In contrast, steroids having a C20 ketone
      but lacking a C3 ketone (tetrahydrocortisone, tetrahydrocortisol and tetrahydro
      S) became highly inhibitory to endothelial cells only after conjugation to
      heparin. They inhibited [3H]thymidine incorporation by 50% at a steroid
      concentration of 18-30 microM and by 95% at 300 microM. Since
      tetrahydrocortisone, tetrahydrocortisol and tetrahydro S lack glucocorticoid and
      mineralocorticoid activity, they may prove safer alternatives to cortisol for
      prolonged administration, as is likely to be necessary with anti-angiogenic
      therapies.

PMID- 9244181
TI  - The osteoblastic MC3T3-E1 cells synthesized C-terminal propeptide of type I
      collagen, which promoted cell-attachment of osteoblasts.
AB  - In this study, we purified C-terminal propeptide of type I collagen (PICP) from
      the conditioned medium of osteoblastic MC3T3-E1 cells by chromatographic and
      Agarose gel extraction procedures. PICP was confirmed to be present in bone by
      Western blotting using a specific antibody, and was proved to be synthesized by
      osteoblasts with metabolic labeling. PICP promoted cell-attachment of
      osteoblastic MC3T3-E1 cells. We conclude that PICP is synthesized by osteoblasts
      and stored in bone, and that it plays a role in the maintenance of bone cells on
      bone matrix.

PMID- 9244182
TI  - Effects of peroxovanadate and vanadate on insulin binding, degradation and
      sensitivity in rat adipocytes.
AB  - The effects of vanadate and the stable peroxovanadate compound bpV(pic) on
      insulin binding and degradation were investigated in rat adipocytes under
      conditions of ongoing receptor cycling. Both bpV(pic) and vanadate increased 125I
      insulin binding to intact cells through an increase in apparent receptor
      affinity. The maximal effect of bpV(pic) was to increase binding approximately 4
      fold (EC50 0.06 +/- 0.01 mM), whereas vanadate increased binding approximately 2
      fold (EC50 1.4 +/- 0.2 mM). Removal of cell surface insulin-receptor complexes
      with trypsin showed that the effects on binding exerted by bpV(pic) and vanadate
      were due to a similar increase in both cell surface binding and intracellular
      accumulation of radioactivity. Both bpV(pic) and vanadate inhibited the
      degradation of 125I-insulin in medium containing 1% bovine serum albumin. The
      ratio of degraded/intact intracellular 125I-insulin was also markedly reduced by
      these agents, suggesting that they inhibit intracellular insulin-degrading
      proteases. Similar to previous findings with vanadate, bpV(pic) stimulated
      glucose transport and, at low concentrations, enhanced insulin sensitivity. Taken
      together, these data demonstrate that both bpV(pic) and vanadate inhibit insulin
      degradation. In addition, they significantly enhance cell surface insulin binding
      in rat fat cells and this is associated with an improved insulin sensitivity.

PMID- 9244183
TI  - In vivo processing of the precursor of the major exoglucanase by KEX2
      endoprotease in the Saccharomyces cerevisiae secretory pathway.
AB  - We have established the main post-translational modification of the major
      exoglucanase of Saccharomyces cerevisiae as the enzyme progresses through the
      secretory pathway. The protein portion of the enzyme accumulated by sec18 cells
      was about 2 kDa larger than that of the secreted enzyme. This precursor (form A)
      was stable when maintained in the endoplasmic reticulum but was processed to the
      mature form (form B) before the block imposed by the sec7 mutation. Sec7 cells,
      when incubated at 37 degrees C, accumulated form B first, but upon prolonged
      incubation, form A was preferentially accumulated. When the supply of newly
      synthesized exoglucanase was prevented by the addition of cycloheximide, the
      accumulated A was transformed into B in the presence of altered Sec7p that still
      prevented secretion. Conversion of A into B was prevented in the double mutant
      sec7 kex2-1, indicating that Kex2p is central to the in vivo processing.
      Consistent with this, a KEX2 deletion mutant secreted form A exclusively.
      Conversion of A into B was also prevented in sec7 cells by the presence of
      dinitrophenol, a poison that depletes ATP levels, indicating that processing is
      dependent upon intracellular transport which involves ER --> Golgi and/or, at
      least, one intra-Golgi step(s). It follows that this transport step(s) is
      independent of functional Sec7p.

PMID- 9244184
TI  - Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase,
      on the growth of tumorigenic cell lines in culture.
AB  - N1-guanyl-1,7-diaminoheptane (GC7) is a potent inhibitor of deoxyhypusine
      synthase (DHS), the enzyme that catalyzes the first step in the hypusination of
      eukaryotic translation initiation factor 5A (eIF-5A). Since eIF-5A is the only
      known cellular substrate for DHS and GC7 has been reported to block the
      proliferation of CHO cells, it has been suggested that DHS may be a novel target
      for anti-cancer therapy. In the present study we investigated the
      antiproliferative effect of GC7 on several tumorigenic cell lines under various
      growth conditions. We found that this compound inhibits the proliferation of H9
      cells in suspension culture and the growth of HeLa cells and v-src-transformed
      NIH3T3 cells under both anchorage-dependent and anchorage-independent conditions.
      Moreover, studies with NIH3T3 cells and v-src-transformed NIH3T3 cells show that
      GC7 inhibits the growth of both cell lines in monolayer culture with similar
      potency and could not reverse the transformed phenotype. In addition, the v-src
      transformed cells grown under both anchorage-dependent and anchorage-independent
      conditions showed similar sensitivity toward GC7. These data indicate that GC7
      acts as a general antiproliferative agent and does not appear to preferentially
      target tumorigenic cell types. Cell cycle analysis show that GC7 reduces the CHO
      K1 cell population in the G1-phase of the cell cycle by 42% and increases the
      number of cells in the S-phase by 44%. This cell cycle distribution profile
      strikingly resembles the distribution of cells treated with puromycin. This
      result supports the hypothesis that the synthesis of a subset of proteins
      important for the S-phase progression of CHO-K1 cells might be dependent upon
      hypusinated eIF-5A. Thus the antiproliferative effect of GC7 appears to be
      related to its interference with the progression of cell cycle, which also
      provides a possible explanation for the lack of selectivity of GC7 between
      nontransformed and transformed cell types tested in this study.

PMID- 9244185
TI  - Molecular cloning and sequencing of a cDNA encoding a beta-thyroid hormone
      receptor in muscovy duckling.
AB  - A cDNA clone encoding a beta-thyroid hormone receptor (TRbeta) from muscovy
      duckling liver was isolated and sequenced. Comparison with the chicken TRbeta
      sequence showed a high degree of homology. This cDNA was used as a probe to
      characterize the TRbeta mRNA transcripts expressed in muscovy duckling liver.

PMID- 9244186
TI  - betagamma-Transducin stimulates hydrolysis and synthesis of phosphatidylinositol
      4,5-bisphosphate in bovine rod outer segment membranes.
AB  - T betagamma was shown to stimulate the hydrolysis and synthesis of PtdInsP2 in
      dark-adapted bovine retinal rod outer segments. In contrast, T alphaGDP blocked
      the effect of betagamma-transducin. It was also demonstrated that T betagamma was
      a stimulator of 32P incorporation into PtdInsP2 in ROS. These findings explain
      the modulating actions of GTP and light on PtdInsP2 hydrolysis and synthesis in
      ROS. The possible existence of cross-talk between the cGMP and phosphoinositide
      cascades in retinal rods was discussed.

PMID- 9244187
TI  - Relationship between TGF alpha-induced DNA synthesis and prostaglandin synthesis
      in human HaCaT keratinocytes.
AB  - The relationship between transforming growth factor alpha (TGF alpha)-induced
      cell proliferation and prostaglandin synthesis was investigated using growth
      arrested human keratinocytes of the HaCaT line. Depending on the TGF alpha
      concentration, the stimulation of DNA synthesis (5-fold) was found to be either
      insensitive (at < 10 ng/ml TGF alpha) or sensitive (at > or = 20 ng/ml TGF alpha)
      to inhibition by both indomethacin, an inhibitor of prostaglandin synthases
      (PGHS) 1 and 2 and the PGHS 2-specific inhibitor NS-398. Indomethacin-effected
      inhibition did not correlate with cytotoxicity and was restricted to a narrow
      time window after growth factor administration. The indomethacin- and NS-398
      sensitive mitogenic effect of TGF alpha correlated with an early increase of
      arachidonic acid release and prostaglandin (PGE2, PGF2alpha) synthesis, whereas
      the PGHS inhibitor-insensitive TGF alpha effect did not. TGF alpha-induced
      prostaglandin synthesis was due to a growth factor-induced PGHS-2 activity as
      indicated by its suppression by NS-398. However, attempts to overcome the PGHS
      inhibitor-dependent suppression of TGF alpha-induced DNA synthesis by adding
      prostaglandins (E1, E2, F2alpha, G2) to the cultures proved to be unsuccessful.
      Thus, TGF alpha-induced synthesis of prostaglandins seems not to be involved in
      the mediation of the mitogenic effect of the growth factor on human keratinocytes
      in culture.

PMID- 9244188
TI  - Membrane potential and cytosolic free calcium levels modulate acetylcholine
      induced inositol phosphate production in insulin-secreting BTC3 cells.
AB  - Effects of membrane potential and cytosolic free Ca2+ concentrations ([Ca2+]i) on
      acetycholine (ACh)-induced inositol phosphate production were investigated in
      insulin secreting betaTC3 cells. ACh (10 microM) caused a rapid inositol 1,4,5
      trisphosphate (Ins(1,4,5)P3) production and increase in [Ca2+]i reaching a
      maximum within 5 s. The rise in Ins(1,4,5)P3 production was reduced by 79 +/- 5%
      when [Ca2+]i was kept low in cells loaded with the Ca2+ chelator BAPTA. The ACh
      evoked Ins(1,4,5)P3 production also depended on the membrane potential as it was
      reduced by 31 +/- 6% in cells hyperpolarized by diazoxide, an opener of ATP
      sensitive K+ channels. The Ca2+ ionophore ionomycin caused a rapid increase in
      [Ca2+]i and in the cellular Ins(1,4,5)P3 content. We conclude that stimulation
      induced changes in membrane potential and [Ca2+]i play an important role in
      controlling Ins(1,4,5)P3 production in insulin-secreting betaTC3 cells.

PMID- 9244189
TI  - Protein kinase C inhibits the CAK-CDK2 cyclin-dependent kinase cascade and G1/S
      cell cycle progression in human diploid fibroblasts.
AB  - Serum stimulation of human diploid fibroblast IMR-90 cells leads to
      phosphorylation of p33CDK2 at Thr160 and activation of CDK2 kinase, a necessary
      event for G1/S transition. We report that serum stimulation causes a gradual,
      sustained increase in the activity of CDK-activating kinase (CAK) that
      phosphorylates CDK2 at Thr160, which starts by 5 h after serum stimulation and
      reaches the maximal plateau level at around the G1/S boundary. In this cell type
      addition of phorbol-12, 13-dibutyrate 5 h but not 16 h after serum stimulation
      completely inhibits CDK2 kinase activation and DNA synthesis. Phorbol ester
      treatment does not reduce the protein level of p33CDK2, but does inhibit serum
      stimulated increases in the CAK activity and CDK2 phosphorylation at Thr160. The
      suppression of the CAK activity by the phorbol ester is accompanied by decreases
      in the message levels of both CDK7 and cyclin H, the catalytic and the positive
      regulatory subunit of CAK, respectively. These results indicate that in IMR-90
      cells activation of protein kinase C in the late G1 phase causes cell cycle
      arrest before the G1/S boundary at least in part through downregulation of CAK
      and CAK-mediated CDK2 phosphorylation and activation.

PMID- 9244190
TI  - Involvement of protein kinase C in the modulation of 1alpha,25-dihydroxy-vitamin
      D3-induced 45Ca2+ uptake in rat and chick cultured myoblasts.
AB  - The calciotropic hormone 1alpha,25-dihydroxy-vitamin D3 (1,25(OH)2D3) has been
      shown to stimulate both rat and chick myoblast 45Ca2+ uptake via modulation of
      dihydropyridine-sensitive L-type calcium channels through phosphorylation by the
      cAMP/protein kinase A pathway. We further investigated the involvement of protein
      kinases in 1,25(OH)2D3-signal transduction on cultured myoblasts. The protein
      kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) was found to
      rapidly stimulate myoblast 45Ca2+ uptake, mimicking 1,25(OH)2D3. The effects of
      PMA were time- (1-5 min) and dose (50-100 nM)-dependent, were mimicked by 1,2
      dioctanoylglycerol (DOG) and were specific, since the inactive analogue 4alpha
      phorbol was without effect. Analogously to the hormone, PMA-enhanced 45Ca2+
      uptake was suppressed by the Ca2+-channel blocker nifedipine (5 microM). 1-(5
      isoquinolynsulfonyl)-2-methylpiperazine (H-7), a PKC inhibitor, and down
      regulation of PKC by prolonged exposure to PMA (1 microM, 24 h), abolished both
      PMA and hormone effects on rat and chick cells. As in chick myoblasts,
      1,25(OH)2D3 activated PKC in rat myoblasts, with translocation of activity from
      the cytosol to the cell membrane. Treatment of myoblasts with PMA (100 nM) plus
      1,25(OH)2D3 (1 nM) greatly potentiated 45Ca2+ uptake than either agent alone. PMA
      also increased myoblast cAMP content. These results suggest the involvement of
      PKC in the mechanism by which 1,25(OH)2D3 rapidly stimulates calcium uptake in
      both mammalian and avian myoblasts.

PMID- 9244191
TI  - Regulation of heparin-binding EGF-like growth factor expression by phorbol ester
      in a human hepatoma-derived cell line.
AB  - Heparin-binding EGF-like growth factor (HB-EGF) is a recently identified potent
      mitogen for smooth muscle cells and fibroblasts. HB-EGF has been shown to be an
      EGF receptor ligand, and also to stimulate epithelial cell growth. A human
      hepatoma-derived cell line, Mahlavu, was analyzed for the production of HB-EGF
      mRNA and active HB-EGF protein. It was found that the cell line synthesized very
      low or undetectable basal level of HB-EGF mRNA. However, the addition of 12-O
      tetradecanoylphorbol-13-acetate (TPA) led to a rapid and transient rise in HB-EGF
      mRNA level. HB-EGF in Mahlavu cells appears to be regulated by a protein kinase C
      (PKC) pathway, since PKC inhibitors, H7, staurosporin, and calphostin C,
      abrogated the induction of HB-EGF mRNA by TPA. Unlike vascular smooth muscle
      cells, induction of HB-EGF gene transcription by TPA was blocked completely by
      incubation with cycloheximide, suggesting that protein synthesis may be a
      prerequisite for HB-EGF gene transcription in Mahlavu cells. Mahlavu cells were
      also found to release a bioactive HB-EGF-like protein into conditioned medium
      which stimulates DNA synthesis in EP170.7 cells. This activity was neutralized by
      an anti-HB-EGF antibody. These results indicate that HB-EGF gene transcription is
      regulated via a PKC pathway, resulting in secretion of active HB-EGF into the
      culture medium of hepatoma-derived Mahlavu cells.

PMID- 9244192
TI  - Desensitization and internalization of adenosine A1 receptors in rat brain by in
      vivo treatment with R-PIA: involvement of coated vesicles.
AB  - Chronic treatment of rats with R-PIA 'in vivo' desensitized adenosine A1 receptor
      mediated inhibition of adenylyl cyclase in brain plasma membranes and increased
      basal and forskolin-stimulated adenylyl cyclase. The adenosine A1 receptor
      agonist CHA (cyclohexyl adenosine) inhibited forskolin-stimulated adenylyl
      cyclase in synaptic plasma membranes from control rats but failed to do so in
      membranes isolated from rats treated with R-PIA. This loss of response was
      accompanied with a significant decrease in both, total number of adenosine A1
      receptors and steady-state level of alpha-Gi in synaptic plasma membranes. An
      increase in the steady-state level of alpha-Gs in synaptic plasma membranes was
      also observed by R-PIA treatment. Concurrently, a significant increase of
      adenosine A1 receptors was observed in microsomes and coated vesicles. These
      results demonstrate adenosine A1 receptor desensitization in rat brain by 'in
      vivo' treatment with R-PIA and suggest a role for coated vesicles in the
      internalization of G-protein coupled receptors.

PMID- 9244193
TI  - Meeting highlights: 46th Annual Scientific Sessions of the American College of
      Cardiology.

PMID- 9244194
TI  - Are we training too many cardiologists?

PMID- 9244195
TI  - Derangements of the nitric oxide synthase pathway, L-arginine, and cardiovascular
      diseases.

PMID- 9244196
TI  - Stent restenosis: can effective antithrombotic therapy be protective?

PMID- 9244197
TI  - Significance of sustained ventricular arrhythmias in patients with valvular heart
      disease.

PMID- 9244198
TI  - BNP: increasing importance in the pathophysiology and diagnosis of congestive
      heart failure.

PMID- 9244199
TI  - Evolution of echocardiographic findings in the fetus.

PMID- 9244200
TI  - Resurrection after mechanical circulatory support.

PMID- 9244201
TI  - Activation of monocyte/macrophage functions related to acute atheroma
      complication by ligation of CD40: induction of collagenase, stromelysin, and
      tissue factor.
AB  - BACKGROUND: Plaque disruption with thrombosis commonly causes the acute coronary
      syndromes. Macrophages, abundant at sites of plaque rupture, release proteinases
      that weaken plaques and express tissue factor (TF), which initiates thrombosis.
      The signals that induce expression of these macrophage functions, particularly
      TF, remain obscure. Recent studies have localized the receptor CD40 and its
      ligand in human atheroma. This study tested the hypothesis that ligation of CD40
      can activate key mononuclear phagocyte functions related to clinical
      manifestations of atheroma. METHODS AND RESULTS: Stimulation of human
      monocytes/macrophages through CD40 by either membranes from activated T cells or
      recombinant CD40L (rCD40L) induced expression of interstitial collagenase,
      stromelysin, and TF protein and activity. In contrast, the soluble cytokines
      interleukin-1 or tumor necrosis factor-alpha did not induce or weakly induced TF
      expression. Neutralization with anti-CD40L antibody markedly inhibited these
      actions of both T-cell membranes and rCD40L. CONCLUSIONS: By inducing the
      expression of matrix-degrading proteinases and of TF procoagulant, CD40 signaling
      may contribute to the triggering of acute coronary events.

PMID- 9244203
TI  - Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin
      in male survivors of myocardial infarction.
AB  - BACKGROUND: The clinical significance of the association between elevated anti
      Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is
      unclear. We explored the relationship between antibodies against Cp and future
      cardiovascular events in male survivors of myocardial infarction (MI). The effect
      of azithromycin antibiotic therapy was assessed in a subgroup of post-MI
      patients. METHODS AND RESULTS: We screened 220 consecutive male survivors of MI
      for anti-Cp antibodies. Of these, 213 patients were stratified into three groups:
      group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate
      titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at > or =
      1/64 dilution. Patients with persisting seropositivity of > or = 1/64 were
      randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or
      500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20)
      represented patients not recruited into the antibiotic trial. The incidence of
      adverse cardiovascular events (over a mean follow-up period of 18+/-4 months) was
      recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp
      I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P
      groups had a fourfold-increased risk for adverse cardiovascular events compared
      with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to
      15.5; P=.03). In contrast, the OR for cardiovascular events in patients receiving
      azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve
      group (OR, 0.9; 95% CI, 0.2 to 4.6, P=NS). Patients receiving azithromycin were
      more likely to experience a decrease in IgG anti-Cp titres than were those in the
      placebo group (P=.02). CONCLUSIONS: An increased anti-Cp antibody titre may be a
      predictor for further adverse cardiovascular events in post-MI patients. Taking a
      short course of azithromycin may lower this risk, possibly by acting against Cp.

PMID- 9244202
TI  - Adenovirus-mediated gene transfer reconstitutes depressed sarcoplasmic reticulum
      Ca2+-ATPase levels and shortens prolonged cardiac myocyte Ca2+ transients.
AB  - BACKGROUND: Decreased expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase
      of the cardiac myocyte (SERCA2) and abnormal Ca2+ regulation have been
      independently linked to human heart failure. This study was designed to determine
      whether expression of a SERCA2 transgene could reconstitute depressed cardiac
      myocyte SERCA2 levels, augment SR Ca2+ uptake, and shorten prolonged excitation
      contraction (EC)-associated Ca2+ transients in neonatal rat cardiac myocytes
      (NM). METHODS AND RESULTS: Cultured NM were treated with phorbol-12-myristate-13
      acetate (PMA), a compound that decreases endogenous SERCA2 expression and results
      in prolongation of EC-associated Ca2+ transients. PMA-treated NM had a 75%
      reduction in SERCA2 mRNA and a 40% reduction in SERCA2 protein levels. SERCA2
      adenovirus infection increased SERCA2 mRNA expression to 2.5 times control and
      reconstituted SERCA2 protein levels in PMA-treated cells. This reconstitution was
      associated with a 32.4% reduction in the time for decline of the Indo-1 Ca2+
      transient to half-maximum levels (t(1/2) [Ca2+]i) (P<.05). A 34.5% augmentation
      of oxalate-facilitated SR Ca2+ uptake was also documented in SERCA2 adenovirus
      infected cells (P<.05). CONCLUSIONS: Adenovirus-mediated expression of a SERCA2
      transgene can reconstitute depressed endogenous SERCA2 levels, shorten prolonged
      Ca2+ transients, and augment SR Ca2+ uptake. It is conceivable that such an
      approach might be used in vivo to normalize altered Ca2+ regulation in human
      heart failure.

PMID- 9244204
TI  - Reduction of restenosis after angioplasty in an atheromatous rabbit model by
      suicide gene therapy.
AB  - BACKGROUND: Gene delivery of the thymidine kinase (tk) gene combined with
      ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries.
      However, the low efficiency of adenoviral-mediated gene transfer to
      atherosclerotic arteries has raised concerns about the applicability of this
      strategy to the prevention of restenosis. METHODS AND RESULTS: A replication
      defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective
      toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic
      cleavage suggesting apoptosis. In vivo, after demonstration of tk expression
      after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested
      in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8
      atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk
      (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days
      2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric
      analysis demonstrated a reduced intima-to-media ratio in the group receiving
      combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5,
      P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury.
      CONCLUSIONS: In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV
      treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions
      reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during
      angioplasty of atheromatous arteries.

PMID- 9244205
TI  - Myocardial infarction in young women in relation to plasma total homocysteine,
      folate, and a common variant in the methylenetetrahydrofolate reductase gene.
AB  - BACKGROUND: In a population-based study, we examined the relationship between the
      risk of myocardial infarction (MI) among young women and plasma total
      homocysteine (tHCY), folate, vitamin B12, and a common cytosine (C) to thymine
      (T) polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase
      (MTHFR). METHODS AND RESULTS: In-person interviews and nonfasting blood samples
      were obtained from 79 women < 45 years old diagnosed with MI and 386
      demographically similar control subjects living in western Washington state
      between 1991 and 1995. Compared with control subjects, case patients had higher
      mean tHCY concentrations (13.4+/-5.2 versus 11.1+/-4.4 micromol/L, P=.0004) and
      lower mean folate concentrations (12.4+/-13.4 versus 16.1+/-12.2 nmol/L, P=.018).
      There was no difference in vitamin B12 concentrations between case patients and
      control subjects (346.8+/-188.4 versus 349.7+/-132.4 pmol/L, P=.90). After
      adjusting for cardiovascular risk factors, we found that women with tHCY > or =
      15.6 micromol/L were at approximately twice the risk of MI as women with tHCY <
      10.0 micromol/L (OR, 2.3; 95% CI, 0.94 to 5.64). Women with folate > or = 8.39
      nmol/L had an approximately 50% lower risk of MI than women with folate < 5.27
      nmol/L (OR, 0.54; 95% CI, 0.23 to 1.28). There was no association with vitamin
      B12 concentration. Among control subjects, 12.7% were homozygous for the MTHFR
      T677 allele, and these women had higher plasma tHCY and lower plasma folate than
      women with other genotypes. Ten percent of case patients were homozygous for the
      T677 allele, and there was no association of homozygosity for T677 with MI risk
      (OR, 0.90; 95% CI, 0.31 to 2.29). CONCLUSIONS: These data support the hypothesis
      that elevated plasma tHCY and low plasma folate are risk factors for MI among
      young women. Although homozygosity for MTHFR T677 is related to increased plasma
      tHCY and low plasma folate, this genetic characteristic is not a risk factor for
      MI in this population.

PMID- 9244206
TI  - Cardiovascular risk factors in Mexican-American and non-Hispanic white children:
      The Corpus Christi Child Heart Study.
AB  - BACKGROUND: Information concerning differences in cardiovascular disease risk
      factors between Mexican-American and non-Hispanic white children is limited. We
      conducted a study to determine if there were ethnic differences in cardiovascular
      disease risk factors in children and whether such differences were explained by
      differences in body mass index. METHODS AND RESULTS: Fasting glucose, insulin,
      and blood lipid concentrations, blood pressure, weight, and height were measured
      in a cross-sectional survey among 403 third-grade children in Corpus Christi,
      Tex. We found significantly higher fasting insulin and glucose concentrations
      among Mexican-American than among non-Hispanic white children. Mexican-American
      boys had slightly lower levels of HDL cholesterol and higher systolic blood
      pressure than non-Hispanic white boys. Ethnic differences in insulin and glucose
      were not explained by body mass index. CONCLUSIONS: These results provide
      preliminary evidence that ethnic differences in insulin, glucose, body mass
      index, and other risk factors occur as early as age 8 to 10 years. Additional
      research is warranted on differences in risk factors in Mexican-American and non
      Hispanic white children and the potential importance of insulin in influencing
      the natural history of these characteristics.

PMID- 9244207
TI  - Colocalization of CPP-32 with apoptotic cells in human atherosclerotic plaques.
AB  - BACKGROUND: Apoptosis that has been reported in human atherosclerosis may
      contribute to the remodeling of atherosclerotic plaques. The identification of
      specific markers for apoptosis in these plaques would permit the development of
      specific therapeutic strategies to limit their progression. Cysteine protease CPP
      32 is essential for apoptotic death in mammalian cells and appears to be an
      attractive candidate. METHODS AND RESULTS: We studied 12 atherosclerotic plaques
      from 12 patients who underwent carotid endarterectomy. Apoptosis was analyzed by
      in situ end labeling of fragmented DNA (TUNEL method) and corroborated by the
      presence of DNA fragmentation in agarose gel electrophoresis. CPP-32 was detected
      with the use of a specific monoclonal antibody, and its expression was compared
      with that of interleukin-1beta-converting enzyme (ICE). We showed that CPP-32 was
      highly expressed in 10 of 12 atherosclerotic plaques and that it colocalized with
      apoptotic cells. Expression of ICE generally paralleled that of CPP-32, but ICE
      was also detected in plaques negative for CPP-32 and showing no apoptosis.
      CONCLUSIONS: CPP-32 is highly expressed within human atherosclerotic plaques and
      is closely related to apoptosis. This finding suggests that CPP-32 may be the ICE
      like enzyme responsible for apoptosis in human atherosclerosis and opens new
      perspectives for the development of therapeutic strategies to alter the
      progression of this disease.

PMID- 9244209
TI  - In-hospital outcome of elderly patients with acute inferior myocardial infarction
      and right ventricular involvement.
AB  - BACKGROUND: There are some specific high-risk subgroups of patients with acute
      inferior myocardial infarction, such as older patients and those with right
      ventricular involvement. However, the clinical implications of right ventricular
      infarction in elderly subjects have not been studied previously. METHODS AND
      RESULTS: To determine the clinical impact of right ventricular involvement in
      elderly patients with inferior myocardial infarction, we studied the in-hospital
      outcome of 198 consecutive patients > or = 75 years of age with a first acute
      inferior myocardial infarction according to the presence of ECG or
      echocardiographic criteria of right ventricular infarction. In patients with
      right ventricular involvement (41%), in-hospital case fatality rate was 47%
      (mainly because of nonreversible low cardiac output cardiogenic shock) compared
      with 10% in patients without right ventricular involvement (P<.001). Patients
      with right ventricular involvement also had a significantly higher incidence of
      cardiogenic shock (32% versus 5%), which was independent of left ventricular
      ejection fraction, complete AV block (33% versus 9%), and interventricular septal
      rupture (9% versus 0%). After adjustment for age, sex, diabetes, shock on
      admission, left ventricular systolic dysfunction, and complete AV block, right
      ventricular infarction remained a powerful independent predictor of in-hospital
      death (adjusted odds ratio, 4.0; 95% confidence interval, 1.3 to 14.2).
      CONCLUSIONS: Elderly patients with acute inferior myocardial infarction have a
      substantially increased risk of death during hospitalization when right
      ventricular involvement is present. The poorer outcome is due mainly to the high
      incidence of cardiogenic shock and its infrequent reversibility.

PMID- 9244208
TI  - Functional evaluation of lipid-lowering therapy by pravastatin in the Regression
      Growth Evaluation Statin Study (REGRESS)
AB  - BACKGROUND: Lipid-lowering therapy during 2 years in the Regression Growth
      Evaluation Statin Study (REGRESS) was associated with less progression of
      coronary atherosclerosis in the pravastatin group compared with the placebo
      group. The effect of lipid-lowering therapy on the functional state of the
      coronary circulation is less well known. The purpose of this study was to
      evaluate this effect. METHODS AND RESULTS: In a substudy of REGRESS, 69 patients
      were randomized to pravastatin or placebo. Thirty-seven of these patients were
      allocated to the medical management stratum. Quantitative coronary angiography,
      regional myocardial perfusion, exercise testing, and classification of angina
      pectoris were assessed at baseline and after 2 years of therapy. Regional
      myocardial perfusion was assessed by digital subtraction angiography after
      intracoronary papaverine with video-densitometric calculation of the hyperemic
      mean transit time (HMTT) of contrast. In the medical management stratum, regional
      myocardial perfusion was assessed in 31 regions in the pravastatin group and 25
      regions in the placebo group. The change in HMTT in the pravastatin group was 
      0.18 seconds (-5%) and in the placebo group +0.52 seconds (+18%), a difference of
      0.70 seconds (P=.004). The mean difference in change in classification of angina
      pectoris (scale, 1 to 4) between pravastatin and placebo was 0.7 (P=.03) in favor
      of the pravastatin-treated patients. The change in HMTT was correlated with the
      change in exercise time (r=-.65, P=.002). CONCLUSIONS: In patients with
      symptomatic coronary artery disease, treatment with the HMG-coenzyme A reductase
      inhibitor pravastatin during 2 years resulted in a preserved regional myocardial
      perfusion, whereas patients on placebo deteriorated. The classification of angina
      pectoris improved only in patients receiving pravastatin. In lipid-lowering
      therapy, the evaluation of myocardial perfusion by assessment of the HMTT reveals
      a combined measure of functional and structural changes in the coronary
      circulation.

PMID- 9244210
TI  - Effects of ramipril on plasma fibrinolytic balance in patients with acute
      anterior myocardial infarction. HEART Study Investigators.
AB  - BACKGROUND: The long-term administration of ACE inhibitors to selected patients
      with left ventricular dysfunction appears to reduce the incidence of recurrent
      myocardial infarction (MI) and unstable angina pectoris. The mechanisms
      responsible for the reduction in ischemic events are unknown, but likely
      candidates include effects on the atherosclerotic process, thrombosis, and/or
      vascular tone. METHODS AND RESULTS: The effects of ACE inhibitor therapy with
      ramipril on plasma fibrinolytic variables were assessed in 120 subjects
      participating in the Healing and Early Afterload Reduction Therapy (HEART) study,
      a double-blind, placebo-controlled trial of acute anterior MI patients who were
      randomly assigned within 24 hours of the onset of symptoms to receive low-dose
      ramipril (0.625 mg daily), full-dose ramipril (1.25 mg titrated to 10 mg/d), or
      placebo for 14 days. Plasma levels of plasminogen activator inhibitor-1 (PAI-1)
      activity and PAI-1 antigen and tissue plasminogen activator (TPA) antigen were
      measured before randomization and on day 14. Clinical characteristics of the
      three study groups were similar, as were the prerandomization plasma levels of
      PAI-1 antigen, PAI-1 activity, and TPA antigen. Compared with the placebo group,
      PAI-1 antigen levels were 44% lower (P=.004) at day 14 in the ramipril-treated
      patients, and PAI-1 activity levels were 22% lower (P=.02). In contrast, plasma
      TPA levels were not significantly different between the placebo-treated and
      ramipril-treated groups. CONCLUSIONS: Treatment with ramipril has a significant
      impact on plasma fibrinolytic variables during the recovery phase after acute MI.
      The renin-angiotensin system appears to play an important role in the regulation
      of vascular fibrinolysis, and interruption of this regulatory pathway may
      contribute to the clinical benefits of ACE inhibitors.

PMID- 9244211
TI  - Relationship between progressive microvascular damage and intramyocardial
      hemorrhage in patients with reperfused anterior myocardial infarction: myocardial
      contrast echocardiographic study.
AB  - BACKGROUND: Recent studies indicated that ischemic microvascular damage may be
      reversible or progressive after coronary reflow. Intramyocardial hemorrhage is a
      phenomenon that reflects severe microvascular injury. We examined the
      relationship between temporal changes in microvascular perfusion patterns
      detected by myocardial contrast echocardiography (MCE) and intramyocardial
      hemorrhage detected by magnetic resonance imaging (MRI) in patients with acute
      myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted
      of 24 patients with anterior AMI. All patients underwent MCE shortly after reflow
      and in the chronic stage (a mean of 31 days after reflow). Wall motion score
      (WMS) was determined as the sum of 16 segmental scores (dyskinetic/akinetic=3 to
      normal=0) at days 1 and 31. Gradient-echo acquisition and gadolinium-DTPA
      enhanced spin-echo MRI were performed within 10 days after reflow. In MCE shortly
      after reflow, 16 patients (67%) showed contrast enhancement and the other 8
      patients (33%) showed a sizable contrast defect. In the chronic stage, a
      persistent contrast defect was observed in 7 of 8 patients with a contrast defect
      shortly after reflow. Consistent contrast enhancement was observed in 12 of 16
      patients (75%) with contrast enhancement shortly after reflow, indicating that a
      contrast defect newly appeared in 4 patients (25%). Intramyocardial hemorrhage
      was detected in 9 patients (38%): 5 of 7 patients with a persistent contrast
      defect and in all 4 patients with a new appearance of a contrast defect during
      the chronic stage. The patients without hemorrhage showed a significant
      improvement in WMS compared with patients with hemorrhage at day 31 (5+/-5 versus
      19+/-6, P<.0005). CONCLUSIONS: These results suggest that irreversible
      microvascular damage to the ischemic myocardium may cause intramyocardial
      hemorrhage after reflow, associated with impaired recovery of left ventricular
      function. Contrast enhancement within the risk area shortly after reflow does not
      necessarily indicate long-term microvascular salvage.

PMID- 9244213
TI  - Restenosis after coronary stent placement and randomization to a 4-week combined
      antiplatelet or anticoagulant therapy: six-month angiographic follow-up of the
      Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial.
AB  - BACKGROUND: Platelets and mural thrombus at the lesion site may play a key role
      in initiating the restenosis process after coronary interventions. The ISAR Trial
      provides a comparison of the outcomes of patients randomized to two different
      antithrombotic regimens administered for 4 weeks after successful coronary stent
      placement: combined antiplatelet therapy (aspirin plus ticlopidine) or a
      conventional anticoagulant regimen (phenprocoumon with initial overlapping
      heparin plus aspirin). Within the first 4 weeks after stent placement, combined
      antiplatelet therapy has been associated with a significant reduction of ischemic
      complications. In the present study, we examined whether combined antiplatelet
      therapy administered for 4 weeks after stent placement is able to reduce the
      process of restenosis at 6 months. METHODS AND RESULTS: Of 517 patients initially
      randomized, 496 were eligible for 6-month angiographic follow-up. Scheduled
      angiography was performed in 432 of the eligible patients (87.1%), 216 in each
      group. In a comparison of the two groups, there were no significant differences
      in clinical and procedural variables or in qualitative and quantitative lesion
      characteristics before and after stenting. At 6 months, minimal luminal diameter
      was 1.95+/-0.86 mm in the group with initial combined antiplatelet therapy and
      1.90+/-0.87 mm in the group with initial anticoagulant therapy (P=.55). Late
      lumen loss was 1.10+/-0.81 and 1.15+/-0.75 mm (P=.54), and the restenosis rate
      was 26.8% and 28.9%, respectively (P=.70). Target lesion revascularization rate
      was 14.6% in the antiplatelet therapy group and 15.6% in the anticoagulant
      therapy group (P=.85). CONCLUSIONS: This study shows that combined antiplatelet
      therapy (aspirin plus ticlopidine) administered for 4 weeks after coronary Palmaz
      Schatz stent placement does not result in a detectable benefit for the prevention
      of restenosis compared with conventional anticoagulant therapy (phenprocoumon
      with initial overlapping heparin plus aspirin).

PMID- 9244212
TI  - Impaired endothelial function in epicardial coronary arteries after Kawasaki
      disease.
AB  - BACKGROUND: Intimal lesions observed in the coronary arteries (CAs) of patients
      who have suffered episodes of Kawasaki disease (KD) raise concern about the
      premature development of arteriosclerosis. Accordingly, we investigated
      endothelial function in the epicardial and resistance CAs after KD during long
      term observation. METHODS AND RESULTS: We assessed the responses of left
      epicardial and resistance CAs to serial intracoronary infusions of acetylcholine
      (final concentrations, 0.1 and 1 micromol/L) and nitroglycerin in subjects by
      using quantitative angiography and a Doppler flow wire system. Three age-matched
      groups were evaluated: 8 control subjects (group 1), 10 KD patients with normal
      left CA from the onset (group 2), and 8 KD patients with a persistent or
      regressed aneurysm in the left anterior descending CA (LAD) (group 3).
      Acetylcholine (1 micromol/L) changed the LAD area to 114.0+/-2.6%, 72.7+/-3.9%
      (P<.05 versus group 1), and 88.9+/-4.3% (P<.05 versus groups 1 and 2) of baseline
      in groups 1, 2, and 3, respectively, with a similar degree of increased coronary
      blood flow in each group. Nitroglycerin increased the LAD area to 143.5+/-7.7%,
      132.3+/-1.9%, and 120.8+/-5.6% (P<.05 versus group 1), respectively. CONCLUSIONS:
      Results demonstrate a persistent endothelial dysfunction in the epicardial but
      not resistance CAs in patients after KD and enhanced stiffness of persistent or
      regressed aneurysms. The concern over early arteriosclerosis warrants the
      surveillance of KD patients from childhood to adulthood.

PMID- 9244214
TI  - Late regression of the dilated site after coronary angioplasty: a 5-year
      quantitative angiographic study.
AB  - BACKGROUND: Limited data are available on the changes that occur at the dilated
      site late after coronary angioplasty. The aim of this study was to evaluate with
      quantitative angiography the natural history of changes that occur in the dilated
      segment between "early" (approximately 6 months) and "late" (approximately 5
      years) follow-up after angioplasty. METHODS AND RESULTS: Of 127 consecutive
      patients (174 lesions) with successful angioplasty, 125 underwent early
      angiography. Three patients subsequently died, and 24 underwent revascularization
      surgery or repeated angioplasty, giving a study-eligible population of 98
      patients. Quantitative angiographic analysis was performed before and immediately
      after angioplasty and at early and late follow-up in the study population of 84
      patients (115 lesions), which was 86% of study-eligible patients. Mean lesion
      diameter stenosis decreased from 36.3+/-14.2% at early to 29.6+/-13.5% at late
      follow-up (P<.0001). No lesion developed late restenosis by the 50% diameter loss
      criterion. Late regression was related to stenosis severity at early angiography
      (r=-.58, P<.001). Subgroups at early angiography of 40% to 49% stenosis and > or
      = 50% stenosis showed significant regression at late angiography. CONCLUSIONS:
      Lesion regression at the dilated site is common late after angioplasty. The more
      severe a stenosis is at early angiography, the more likely the chance that there
      will be late regression. A strategy of watchful waiting may be appropriate for
      patients with restenotic lesions of borderline severity.

PMID- 9244215
TI  - Remodeling of human coronary arteries undergoing coronary angioplasty or
      atherectomy.
AB  - BACKGROUND: Recently, long-term constriction of the vessel has been suggested as
      an alternative mechanism of restenosis after coronary angioplasty. METHODS AND
      RESULTS: To understand remodeling of human coronary arteries undergoing coronary
      angioplasty or atherectomy, serial intravascular ultrasonographic examinations
      were performed at preintervention and postintervention examinations and at 24
      hours, 1 month, and 6 months. Complete serial data were obtained in 61 lesions
      (balloon angioplasty, 35 lesions; directional atherectomy, 26 lesions). Lumen
      area improved from 6.81+/-2.24 mm2 after intervention to 8.22+/-2.79 mm2 at 1
      month (P=.0001) and decreased to 4.88+/-2.86 mm2 at 6 months (P=.0001). Vessel
      area enlarged from 17.32+/-5.35 mm2 after intervention to 19.39+/-5.33 mm2 at 1
      month (P=.0001) and decreased to 16.33+/-5.54 mm2 at 6 months (P=.0001).
      Plaque+media area increased significantly from postintervention examination to 24
      hours (10.51+/-4.38 versus 10.96+/-4.49 mm2, P=.0008) and from 24 hours to 6
      months (10.96+/-4.49 versus 11.45+/-4.45 mm2, P=.03). Changes in lumen area in
      each study interval correlated more closely with changes in vessel area than with
      changes in plaque+media area. Restenotic lesions compared with nonrestenotic
      lesions had a greater decrease in the vessel area between 1 month and 6 months (
      4.33+/-2.73 versus -2.49+/-2.15 mm2, P=.006) and greater increase in the
      plaque+media area both within 24 hours (0.84+/-1.22 versus 0.27+/-0.38 mm2,
      P=.04) and between 24 hours and 6 months (1.19+/-2.19 versus 0.18+/-1.46 mm2,
      P=.04). CONCLUSIONS; Remodeling after coronary angioplasty or atherectomy was
      characterized by early adaptive enlargement and late constriction of the vessel.

PMID- 9244216
TI  - Intracoronary Doppler assessment of moderate coronary artery disease: comparison
      with 201Tl imaging and coronary angiography. FACTS Study Group.
AB  - BACKGROUND: Coronary angiography may not reliably predict whether a stenosis
      causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance
      diagnostic accuracy by providing a physiological assessment of stenosis severity.
      The goal of this study was to compare intracoronary Doppler ultrasound with both
      201Tl imaging and coronary angiography. METHODS AND RESULTS: Fifty-five patients
      with 67 stenotic coronary arteries underwent coronary angiography with
      intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week
      period. Coronary flow reserve was measured, and analyses were performed by
      independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses
      were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7
      predicted the presence of a stress 201Tl defect in 56 of 67 stenoses
      (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved
      75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data
      agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97).
      Scatter was evident when angiography was compared with coronary flow reserve
      (r=.43), and the angiogram did not reliably predict the results of the 201Tl
      stress test (kappa=0.21; agreement=57% to 63%). CONCLUSIONS: Doppler-derived
      coronary flow reserve accurately predicts the presence of exercise-induced
      ischemia on stress 201Tl imaging, and coronary angiography does not reliably
      assess the physiological significance of an intermediate coronary stenosis.

PMID- 9244217
TI  - Comparison of coronary luminal quantification obtained from intracoronary
      ultrasound and both geometric and videodensitometric quantitative angiography
      before and after balloon angioplasty and directional atherectomy.
AB  - BACKGROUND: Debate exists regarding the relationship between angiographic and
      intracoronary ultrasound (ICUS) measurements of minimal luminal cross-sectional
      area after coronary intervention. We investigated this and the factors that may
      influence it by using ICUS and quantitative angiography. METHODS AND RESULTS:
      Patients who underwent successful balloon angioplasty (n=100) or directional
      atherectomy (n=50) were examined by using ICUS and quantitative angiography (edge
      detection [ED] and videodensitometry [VID]) before and after intervention.
      Luminal damage postintervention was qualitatively graded into three categories
      based on angiographic results (smooth lumen, haziness, or dissection).
      Correlation of minimal luminal cross-sectional area measurements by ICUS and ED
      was .59 before and .47 after balloon angioplasty. Correlation between ICUS and
      VID was .50 before and .63 after balloon angioplasty. Postintervention, the
      difference between ICUS and VID was less than the difference between ICUS and ED
      (P<.01). Additionally, the correlation was .74 between ICUS and ED measurements
      and .78 between ICUS and VID measurements in the smooth lumen group, .46 and .63,
      respectively, in the presence of haziness, and .26 and .46, respectively, in
      lesions with dissection. Similar results were obtained after directional
      atherectomy: the agreement between ICUS and quantitative angiography deteriorated
      according to the degree of vessel damage, but less so with VID than ED.
      CONCLUSIONS: Complex morphological changes induced by intervention may contribute
      to discordance between the two quantitative imaging techniques. In the absence of
      ICUS, VID may be a complementary technique to ED in lesions with complex
      morphology after balloon angioplasty and directional atherectomy.

PMID- 9244218
TI  - Patients with valvular heart disease presenting with sustained ventricular
      tachyarrhythmias or syncope: results of programmed ventricular stimulation and
      long-term follow-up.
AB  - BACKGROUND: Programmed ventricular stimulation is commonly used to guide therapy
      in post-myocardial infarction patients with sustained monomorphic ventricular
      tachycardia (VT) or ventricular fibrillation (VF). In patients with valvular
      heart disease presenting with spontaneous VT, VF, or syncope, the usefulness of
      this technique is still unclear. The aim of the study was to analyze whether
      programmed ventricular stimulation was helpful in guiding therapy and determining
      prognosis in 97 patients with valvular heart disease presenting with VT (60%), VF
      (18%), or syncope (22%). METHODS AND RESULTS: Patients were classified as having
      either predominant ventricular pressure or volume overload or no significant
      pressure or volume overload. Overall, sustained VT or VF was inducible in 38
      (39%) and 19 (20%) patients, respectively. Forty-six (47%) patients were
      discharged on antiarrhythmic drugs, 29 (30%) received an implantable cardioverter
      defibrillator, and 22 (23%) remained without therapy. With serial drug testing,
      inducibility was completely or partially suppressed in 18 (19%) and 9 (9%)
      patients, respectively. During a mean follow-up of 51 months (n=97), 17 patients
      (18%) died (sudden death, n=7; heart failure, n=4; noncardiac causes, n=6). One-,
      2- and 3-year event-free survival for sudden death, sustained VT, or VF was 77%,
      68%, and 61%, respectively. Only inducibility of VT during baseline study
      (P<.0003) and left ventricular volume overload (P<.008) were significant
      predictors of arrhythmic events. Recurrence of arrhythmic events occurred in 56%
      and 56% of patients with complete or partial suppression of inducibility during
      serial drug testing as well as in 10 of 19 (53%) patients without a change in
      inducibility. CONCLUSIONS: Although programmed ventricular stimulation seems to
      predict adverse outcome, serial drug testing is unreliable in guiding therapy.
      The type of workload imposed on the ventricles influences outcome, being worse in
      patients with left ventricular volume overload. Therefore, implantation of a
      cardioverter-defibrillator should be considered early for the management of these
      patients.

PMID- 9244219
TI  - Attenuation of compensation of endogenous cardiac natriuretic peptide system in
      chronic heart failure: prognostic role of plasma brain natriuretic peptide
      concentration in patients with chronic symptomatic left ventricular dysfunction.
AB  - BACKGROUND: Patients with congestive heart failure (CHF) have high plasma levels
      of atrial natriuretic peptide (ANP), mainly from the atrium, and brain
      natriuretic peptide (BNP), mainly from the ventricle. We examined the prognostic
      role of plasma BNP in chronic CHF patients in comparison with plasma ANP and
      other variables previously known to be associated with high mortality. We also
      evaluated the relationship between mortality and plasma cGMP, a biological marker
      of ANP and BNP. METHODS AND RESULTS: The study subjects were 85 patients with
      chronic CHF (left ventricular ejection fraction <0.45) who were followed for 2
      years. The plasma levels of ANP, BNP, cGMP, and norepinephrine increased with the
      severity of CHF. Among plasma levels of ANP, BNP, cGMP, and norepinephrine and
      clinical and hemodynamic parameters, only high levels of plasma BNP (P<.0001) and
      pulmonary capillary wedge pressure (P=.003) were significant independent
      predictors of the mortality in patients with CHF by Cox proportional hazard
      analysis. Although plasma levels of ANP and BNP were threefold or fivefold higher
      in nonsurvivors than in survivors, there was no difference in plasma cGMP level
      between nonsurvivors and survivors. CONCLUSIONS: These findings indicate that
      plasma BNP is more useful than ANP for assessing the mortality in patients with
      chronic CHF and that the plasma levels of BNP provide prognostic information
      independent of other variables previously associated with a poor prognosis. Our
      findings also suggest that the compensatory activity of the cardiac natriuretic
      peptide system is attenuated as mortality increases in chronic CHF patients with
      high plasma levels of ANP and BNP.

PMID- 9244220
TI  - Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for
      orthostatic intolerance.
AB  - BACKGROUND: The cardiovascular adaptation to bed rest leads to orthostatic
      intolerance, characterized by an excessive fall in stroke volume (SV) in the
      upright position. We hypothesized that this large fall in SV is due to a change
      in cardiac mechanics. METHODS AND RESULTS: We measured pulmonary capillary wedge
      pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left
      ventricular mass (by echocardiography) at rest, during lower-body negative
      pressure, and after saline infusion before and after 2 weeks of bed rest with -6
      degrees head-down tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V)
      curves were modeled exponentially by P=ae(kV)+b and logarithmically by P=-Sln[(Vm
      V)/(Vm-V0)], where V0 indicates volume at P=0, and the constants k and S were
      used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was
      calculated at baseline LVEDV. The slope of the line relating SV to PCWP during
      lower-body negative pressure characterized the steepness of the Starling curve.
      We also measured plasma volume (with Evans blue dye) and maximal orthostatic
      tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP
      (18%), SV (12%), LVEDV (16%), V0 (33%), and orthostatic tolerance (24%) (all
      P<.05). The slope of the SV/PCWP curve increased from 4.6+/-0.4 to 8.8+/-0.9
      mL/mm Hg (P<.01) owing to a parallel leftward shift in the P-V curve. Normalized
      chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV,
      and cardiac mass tended to be reduced by 5% (P<.10). CONCLUSIONS: Two weeks of
      head-down-tilt bed rest leads to a smaller, less distensible left ventricle but a
      shift to a more compliant portion of the P-V curve. This results in a steeper
      Starling relationship, which contributes to orthostatic intolerance by causing an
      excessive reduction in SV during orthostasis.

PMID- 9244221
TI  - Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and
      their importance for cardiac cachexia.
AB  - BACKGROUND: The role of hormonal and cytokine abnormalities in the development of
      cardiac cachexia remains obscure. METHODS AND RESULTS: Healthy control subjects
      (n=16) and patients with chronic heart failure (CHF), classified clinically as
      cachectic (8% to 35% weight loss over > or = 6 months before study, n=16) or
      noncachectic (n=37), were assessed for markers of disease severity (maximal
      oxygen consumption, left ventricular ejection fraction, NYHA functional class).
      These markers were compared with plasma concentrations of potentially important
      anabolic and catabolic factors. The degree of neurohormonal activation and
      catabolic/anabolic imbalance was closely related to wasting but not to
      conventional measures of the severity of heart failure. Compared with control
      subjects and noncachectic patients, cachectic patients had reduced plasma sodium
      and increased norepinephrine, epinephrine (all P<.0001), cortisol, tumor necrosis
      factor (TNF)-alpha (both P<.002), and human growth hormone (P<.05). Insulin-like
      growth factor-1, testosterone, and estrogen were similar in all groups. Insulin
      was increased only in the noncachectic patients (P<.005 versus control subjects).
      Dehydroepiandrosterone was reduced in the cachectic patients (P<.02 versus
      control subjects). Insulin, cortisol, TNF-alpha, and norepinephrine correlated
      independently with wasting in CHF (P<.05; multiple regression of these four
      factors versus percent ideal weight, R2=.50, P<.0001). CONCLUSIONS: Cachexia is
      more closely associated with hormonal changes in CHF than conventional measures
      of the severity of CHF. This study suggests that the syndrome of heart failure
      progresses to cardiac cachexia if the normal metabolic balance between catabolism
      and anabolism is altered.

PMID- 9244222
TI  - Noninvasive measurement of shortening in the fiber and cross-fiber directions in
      the normal human left ventricle and in idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Studies in anesthetized dogs have shown that myocardial fibers
      shorten approximately 8%. However, in the endocardium, shortening occurs to a
      much greater extent at 90 degrees to the fiber orientation ("cross-fiber
      shortening") than it does along the fiber direction. The purpose of this study
      was to estimate the extent of fiber and cross-fiber shortening in the normal
      human left ventricle and in patients with idiopathic dilated cardiomyopathy
      (IDC). METHODS AND RESULTS: Ten normal subjects and nine patients with IDC were
      imaged with magnetic resonance tissue tagging. Finite strain analysis was used to
      calculate endocardial and epicardial shortening in the fiber and cross-fiber
      directions using anatomic fiber angles from representative autopsy specimens as
      references. Anatomic fiber angles were not different between normal subjects and
      IDC patients. Epicardial fiber strain was -0.14+/-0.01 in normal subjects and 
      0.08+/-0.01 in IDC patients (P<.0001 versus normal subjects). Epicardial cross
      fiber strain was -0.08+/-0.01 in normal subjects and -0.06+/-0.01 in IDC patients
      (P=NS). Endocardial fiber strain was -0.16+/-0.01 in normal subjects and -0.09+/
      0.01 in IDC patients (P<.0001), and endocardial cross-fiber strain was -0.26+/
      0.01 in normal subjects and -0.15+/-0.01 in IDC patients (P<.0001). Cross-fiber
      shortening was greater than fiber shortening at the endocardium in both normal
      subjects (P<.0001) and IDC patients (P<.05). CONCLUSIONS: In normal humans, the
      direction of maximal deformation aligns with the fiber direction in the
      epicardium but is perpendicular to the fiber direction in the endocardium. When
      strain in a coordinate system aligned to the fibers is estimated, cross-fiber
      shortening is found to be the dominant shortening strain at the endocardium.
      Normal fiber shortening is 15%, and this is markedly reduced in IDC. The normal
      transition in fiber orientation through the wall is not altered in IDC, and cross
      fiber shortening is still the dominant strain at the endocardium, suggesting that
      interactions between myocardial layers persist in these patients.

PMID- 9244223
TI  - Weaning from mechanical cardiac support in patients with idiopathic dilated
      cardiomyopathy.
AB  - BACKGROUND: Implantation of mechanical cardiac support systems (MCSS) in patients
      with idiopathic dilated cardiomyopathy (IDC) may improve cardiac function and
      allow explantation of the device. We report of long-term effects of ventricular
      unloading on cardiac function, humoral anti-beta1-adrenoceptor autoantibodies (A
      beta1-AABs), and myocardial fibrosis. METHODS AND RESULTS: Seventeen patients in
      New York Heart Association functional class IV with nonischemic IDC received
      MCSS. All had a cardiac index of < 1.6 L x min(-1) x m(-2) of body surface area,
      a left ventricular ejection fraction (LVEF) of <16%, and a left ventricular
      internal diameter in diastole (LVIDd) of >68 mm and tested positive for A-beta1
      AABs. Echocardiographic evaluation, serum tests for A-beta1-AABs, and
      histological assessment of myocardial fibrosis were performed before and after
      MCSS implantation. The mean support duration was 230+/-201 days. Six patients
      died, four were transplanted, and two are still on MCSS. Five patients with
      significant cardiac recovery (mean LVIDd, 54+/-2.3 mm; LVEF, 47+/-3.7%) were
      weaned after 160 to 794 days and are now device free for 51 to 592 days. A-beta1
      AABs disappeared gradually during MCSS without increase after weaning; cardiac
      function and volume density of fibrosis remained normal. Nine patients' cardiac
      function hardly improved during ventricular unloading. CONCLUSIONS: Cardiac
      function can be normalized in selected patients with end-stage IDC by MCSS. The
      degree of preoperative myocardial fibrosis may be an indicator for outcome; A
      beta1-AABs can be used to monitor myocyte recovery. Weaning from MCSS offers an
      alternative to cardiac transplantation in certain patients.

PMID- 9244224
TI  - Congenital heart defects: natural course and in utero development.
AB  - BACKGROUND: Most congenital heart defects (CHDs) are diagnosed on targeted
      prenatal transvaginal (TVS) or transabdominal (TAS) ultrasonography during the
      early second trimester or at midgestation. Nevertheless, delayed diagnosis in
      some cardiac malformations still remains despite detailed echocardiographic
      examination. The present study was conducted to evaluate the evolution of fetal
      cardiac anomalies and assess their development in utero. METHODS AND RESULTS: We
      retrospectively reviewed 22,050 pregnant women who were divided into two groups:
      6924 who had initial TVSs at 13 to 16 weeks' gestation, followed by TASs at 20 to
      22 weeks, and 15,126 who had initial TASs at 20 to 22 weeks. Both groups were
      subsequently examined in their third trimester. All newborns were examined by
      certified pediatricians. CHD was diagnosed in 168 babies: 66 in group A and 102
      in group B. In group A, 42 malformations (64%) were detected at the first TVS
      examination, and 11 (17%) were found during the subsequent TAS. Three additional
      anomalies (4%) were found during the third trimester, and 10 malformations (15%)
      were detected postnatally. In group B, 80 malformations (78%) were detected in
      the initial examination at midtrimester, and an additional 7 (7%) were found in
      the third trimester, whereas 15 (15%) were diagnosed postnatally. The 10
      anomalies (group A, n=3; group B, n=7) that were detected only during the third
      trimester comprised aortic stenosis (n=2), cardiac rhabdomyoma (n=2), subaortic
      stenosis (n=1), tetralogy of Fallot (n= 1), aortic coarctation (n=1), sealed
      foramen ovale (n=1), ventricular septal defects (n=1), and hypertrophic
      cardiomyopathy (n=1). CONCLUSIONS: Although most fetal cardiac anomalies are
      detectable early in gestation, some may evolve in utero at different stages of
      pregnancy.

PMID- 9244225
TI  - Abnormal epinephrine release in young adults with high personal and high parental
      blood pressures.
AB  - BACKGROUND: Increased activity of the sympathetic nervous system has been
      proposed as a cause of high blood pressure (BP) and may be related to diet and
      body weight. To determine the role of these factors in predisposition to high BP,
      we studied 100 young adults with high or low BP from families in which both
      parents had either high or low BP. METHODS AND RESULTS: Plasma catecholamine,
      glucose, and insulin levels were measured before and after an oral glucose load.
      There was a significant correlation between fasting plasma norepinephrine and
      mean arterial pressure (P=.001). Subjects with high BP, irrespective of parental
      BP, were heavier (P=.003) and fatter (P=.002) and had a greater rise in plasma
      insulin (P=.003) following glucose than those with low BP. Offspring with high BP
      whose parents also had high BP showed an unexpected rise in plasma epinephrine
      (P=.004) following glucose. This adrenal medullary response was not the result of
      high parental or high personal BP alone as it was not seen in offspring with low
      BP whose parents had high BP or in offspring with high BP whose parents had low
      BP. CONCLUSIONS: Irrespective of family history, high BP is associated with
      increased body weight and hyperinsulinemia and reflects personal environment and
      behavior. However, abnormal epinephrine release is characteristic of the
      combination of genetic, environmental, and behavioral factors that is associated
      with high personal BP and a familial predisposition to high BP.

PMID- 9244226
TI  - Monitoring considerations for port-access cardiac surgery.
AB  - BACKGROUND: A method for monitoring patients was evaluated in a clinical trial of
      minimally invasive port-access cardiac surgery with closed chest endovascular
      cardiopulmonary bypass. METHODS AND RESULTS: Cardiopulmonary bypass was conducted
      in 25 patients through femoral cannulas. An endovascular pulmonary artery vent
      was placed in the main pulmonary artery through a jugular vein. For mitral valve
      surgery, a catheter was placed in the coronary sinus for delivery of
      cardioplegia. A balloon catheter ("endoaortic clamp," EAC) used for occlusion of
      the ascending aorta, delivery of cardioplegia, aortic root venting, and pressure
      measurement was inserted through a femoral artery and initially positioned by use
      of fluoroscopy and transesophageal echocardiography (TEE). Potential migration of
      the EAC was monitored by (1) TEE of the ascending aorta, (2) pulsed-wave Doppler
      of the right carotid artery, (3) balloon pressure, (4) comparison of aortic root
      pressure and right radial artery pressure, and (5) fluoroscopy. TEE, fluoroscopy,
      and pressure measurement were effective in monitoring catheter insertion and
      position. With inadequate balloon inflation, migration of the EAC toward the
      aortic valve could be detected with TEE. During administration of cardioplegia,
      TEE showed movement of the balloon away from the aortic valve, and migration into
      the aortic arch was detectable with loss of carotid Doppler flow. Stability of
      EAC position was demonstrated with appropriate balloon volume. Cardioplegic
      solution was visualized in the aortic root, and aortic root pressure changed
      appropriately during administration of cardioplegia. Venous cannula position was
      optimized with TEE and endopulmonary vent flow measurement. CONCLUSIONS: An
      effective method has been developed for monitoring patients and the catheter
      system during port-access cardiac surgery.

PMID- 9244227
TI  - Aprotinin inhibits plasmin-induced platelet activation during cardiopulmonary
      bypass.
AB  - BACKGROUND: In the past few years, aprotinin has been used in cardiac surgery
      with impressive results of reducing blood loss, but several adverse effects of
      aprotinin also have been reported. One of the most likely mechanisms is the
      inhibition of plasmin by aprotinin, although this indirect effect has not been
      reproduced in all experimental studies. METHODS AND RESULTS: We evaluated the
      platelet function and fibrinolytic activity during human cardiac surgery, with or
      without aprotinin. During cardiopulmonary bypass (CPB) in humans without
      aprotinin (n=16), decrease of platelet aggregation induced by thrombin, increase
      of alpha-granule secretion of platelet and microparticle formation, and increase
      of plasmin/alpha2-antiplasmin complex (PIC) were observed. In contrast, low-dose
      aprotinin (1.0 x 10(6) KIU), which was administered only into the priming fluid
      of extracorporeal circuits (n=10), maintained platelet aggregation induced by
      thrombin and reduced alpha-granule secretion and microparticle formation of
      platelets during CPB. In vitro, plasmin (0.8 CU/mL) released alpha-granules of
      washed platelets, and this activation was completely inhibited by aprotinin (10
      KIU/mL). CONCLUSIONS: Aprotinin has indirect effects to inhibit platelet
      activation, and this may partly explain the reduction of blood loss during
      cardiac surgery. To prevent the adverse effects, a single and minimal use of
      aprotinin is important. The results of in vivo and in vitro studies suggest that
      platelet preservation was demonstrated by the lower concentration of aprotinin
      (1.0 x 10(6) KIU per patient or 10 KIU/mL) compared with the concentration that
      inhibits plasma fibrinolysis.

PMID- 9244228
TI  - Effects of volume loading and pressor agents in idiopathic orthostatic
      tachycardia.
AB  - BACKGROUND: Idiopathic orthostatic tachycardia (IOT) is characterized by an
      increase in heart rate (HR) with standing of > or = 30 bpm that is associated
      with elevated catecholamine levels and orthostatic symptoms. A dynamic
      orthostatic hypovolemia and alpha1-adrenoreceptor hypersensitivity have been
      demonstrated in IOT patients. There is evidence of an autonomic neuropathy
      affecting the lower-extremity blood vessels. METHODS AND RESULTS: We studied the
      effects of placebo, the alpha1-adrenoreceptor agonist midodrine (5 to 10 mg), the
      alpha2-adrenoreceptor agonist clonidine (0.1 mg), and I.V. saline (1 L) in 13
      patients with IOT. Supine and upright blood pressure (BP) and HR were measured
      before and at 1 and 2 hours after intervention. Midodrine decreased both supine
      and upright HR (all HR values are given as bpm) at 2 hours (from 78+/-2 supine to
      108+/-5 upright before treatment and from 69+/-2 supine to 95+/-5 upright after
      treatment, P<.005 for supine and P<.01 for upright). Saline decreased both supine
      and upright HR (from 80+/-3 supine to 112+/-5 upright before infusion and from
      77+/-3 supine to 91+/-3 upright 1 hour after infusion, P<.005 for supine and
      P<.001 for upright). Clonidine decreased supine HR (from 78+/-2 to 74+/-2, P<.03)
      but did not affect the HR increase with standing. Clonidine very significantly
      decreased supine systolic BP (from 109+/-3 at baseline to 99+/-2 mm Hg at 2
      hours, P<.001), and midodrine decreased supine systolic BP mildly. CONCLUSIONS:
      IOT responds best acutely to saline infusion to correct the underlying
      hypovolemia. Chronically, this can be accomplished with increased salt and water
      intake in conjunction with fludrocortisone. The response of patients to the
      alpha1-agonist midodrine supports the hypothesis of partial dysautonomia and
      indicates that the use of alpha1-agonists to pharmacologically replace lower
      extremity postganglionic sympathetics is an appropriate overall goal of therapy.
      These findings are consistent with our hypothesis that the tachycardia and
      elevated catecholamine levels associated with IOT are principally due to
      hypovolemia and loss of adequate lower-extremity vascular tone.

PMID- 9244229
TI  - Prediction of head-up tilt test result by analysis of early heart rate
      variations.
AB  - BACKGROUND: Head-up tilt testing is a useful test for investigating vasovagal
      syncope. The determination of early, accurate, predictive criteria for a negative
      result would permit a reduction in the duration of the tilt test. METHODS AND
      RESULTS: Patients with no drug use and no illnesses other than recurrent
      unexplained syncope were recruited. In an initial study (110 consecutive
      patients), we aimed to determine a predictive criterion based on heart rate
      variations during the first minutes of upright tilting that could distinguish
      between patients with positive and negative tilt tests (patients with an early
      continual decrease in heart rate or blood pressure were excluded). Then we tested
      the predictive value of the established criterion in a second independent sample
      of patients with unexplained syncope (109 consecutive patients). An early
      sustained increase in heart rate < or = 18 bpm during the first 6 minutes of
      upright tilting at a 60 degree angle allowed us to predict negative tilt tests
      with 100% specificity, 100% positive predictive value, and 88.6% sensitivity.
      This criterion was validated in the second, prospective arm of the study (96.4%
      specificity, 98.4% positive predictive value, and 87.3% sensitivity), even with
      subsequent use of isoproterenol in low doses. CONCLUSIONS: In patients with no
      drug use and no illnesses other than recurrent unexplained syncope, a simple
      clinical criterion identifies patients who will not develop syncope during a
      prolonged upright tilt.

PMID- 9244230
TI  - iNOS expression and nitrotyrosine formation in the myocardium in response to
      inflammation is controlled by the interferon regulatory transcription factor 1.
AB  - BACKGROUND: Production of NO by inducible NO synthase (iNOS) has been implicated
      in the pathology of spontaneous and antigen-induced autoimmune diseases, and iNOS
      is expressed in the myocardium of patients with heart failure. It is not clear
      whether inflammatory murine autoimmune heart disease, an experimental model for
      human postviral heart disease, is characterized by increased iNOS expression
      within the heart and whether iNOS and NO are essential in the pathogenesis of
      autoimmune myocarditis. METHODS AND RESULTS: In the murine model of cardiac
      myosin-induced myocarditis, we demonstrate that iNOS expression was elicited in
      inflammatory macrophages and in distinct cardiomyocytes. Autoimmune heart disease
      was accompanied by formation of the NO reaction product nitrotyrosine in
      inflammatory macrophages as well as in cardiomyocytes. iNOS expression and
      nitrotyrosine formation were strictly dependent on myocardial inflammation. Focal
      myocarditis was sufficient to induce nitrotyrosine formation throughout the whole
      heart muscle. Mice defective for the interferon regulatory transcription factor-1
      (IRF-1(-/-)) after gene targeting failed to induce iNOS expression and
      nitrotyrosine formation in the heart but developed cardiac myosin-induced
      myocarditis at prevalence and severity similar to those of heterozygous
      littermates (IRF-1(+/-)). CONCLUSIONS: These data provide the first in vivo
      evidence that iNOS expression and NO synthesis in macrophages and distinct
      cardiomyocytes are elicited in experimental murine inflammatory heart disease.
      The transcription factor IRF-1 controls iNOS expression and NO synthesis in
      disease. Because autoimmune myocarditis can develop in animals lacking IRF-1,
      these mice will be useful to elucidate the link between iNOS expression in
      inflammatory heart disease and the development of dilated cardiomyopathy and
      heart failure.

PMID- 9244231
TI  - Effects of thyroid hormone on cardiac beta-adrenergic responsiveness in conscious
      baboons.
AB  - BACKGROUND: Many of the cardiovascular manifestations of thyroid hormone excess
      resemble those produced by sympathoadrenal stimulation. The objective of this
      study was to determine the effects of thyroid hormone excess on myocardial beta
      adrenergic expression and responsiveness to infused agonists in the primate
      heart. METHODS AND RESULTS: The responses of left ventricular isovolumic
      contraction (dP/dt(max)) and relaxation (tau) during graded dobutamine infusion
      were studied both before and after 4 weeks of thyroid hormone administration in 8
      chronically instrumented baboons. At matched (atrially paced) heart rates,
      thyroid hormone significantly increased resting dP/dt(max) (3073+/-1034 versus
      2318+/-829 mm Hg/s, P<.05) and decreased tau (24.0+/-5.5 versus 28.2+/-5.4 ms,
      P<.05). The change from baseline for dP/dt(max) and tau in response to beta1
      adrenergic stimulation was significant at each dobutamine dose (2.5 to 10 microg
      x kg(-1) x min(-1)), but when expressed as a percent change, it was similar
      before versus after thyroid hormone. Similar changes were found when beta2
      adrenergic stimulation was produced by terbutaline infusion in three additional
      baboons. beta-Adrenergic receptor (betaAR) expression was higher in five
      thyroxine-treated than in five control baboons (37.4+/-1.2 versus 15.7+/-3.2
      fmol/mg, P<.001), and this was due to a greater increase in the beta2AR (5.9+/
      1.5 to 20.6+/-1.2 fmol/mg, P<.001) than the beta1AR (9.7+/-1.7 to 16.8+/-0.1
      fmol/mg, P<.01) subtype. CONCLUSIONS: In the primate heart, thyroid hormone
      produces positive inotropic and lusitropic effects in the resting state and
      upregulates both beta1AR and beta2AR, with the beta2AR increase predominating. At
      equivalent rates, however, thyroid hormone excess does not appear to enhance the
      sensitivity of left ventricular contractility and relaxation to either beta1- or
      beta2-adrenergic stimulation.

PMID- 9244232
TI  - Inhibition of sarcolemmal Na+,K+-ATPase activity reduces the infarct size
      limiting effect of preconditioning in rabbit hearts.
AB  - BACKGROUND: The inhibition of sarcolemmal Na+,K+-ATPase activity is closely
      related to ischemic myocardial cell injury. However, the involvement of this
      enzyme in preconditioning has not been determined. METHODS AND RESULTS: We
      assessed the effect of ischemia on sarcolemmal Na+,K+-ATPase activity. Control
      and preconditioned rabbits were subjected to 0, 10, 20, 30, and 60 minutes of
      coronary occlusion. Ten to 60 minutes of ischemia reduced Na+,K+-ATPase activity,
      whereas preconditioning preserved the activity of this enzyme only during the
      first 20 minutes of ischemia. To determine whether the preservation of Na+,K+
      ATPase activity in the early phase of ischemia contributed to limiting the
      infarct size, additional rabbits underwent 30 minutes of occlusion followed by 3
      hours of reperfusion with or without pretreatment with digoxin, an inhibitor of
      Na+,K+-ATPase. Infarct size in animals pretreated with digoxin in the absence of
      preconditioning did not differ from that in controls. It was markedly reduced by
      preconditioning, whereas digoxin reduced the infarct size-limiting effect.
      Moreover, preconditioning increased sarcolemmal Na+-Ca2+ exchange activity in
      rabbits subjected to 20 minutes of ischemia, whereas digoxin diminished this
      increase. CONCLUSIONS: Preconditioning preserves the ischemia-induced reduction
      in sarcolemmal Na+,K+-ATPase activity in the early phase of ischemia in rabbit
      hearts. Inhibition of Na+,K+-ATPase activity reduces the infarct size-limiting
      effect of preconditioning with a loss of increased Na+-Ca2+ exchange activity,
      implying that this preservation is responsible for the cardioprotective effect of
      preconditioning.

PMID- 9244233
TI  - Fibrin induction of tissue factor expression in human vascular endothelial cells.
AB  - BACKGROUND: For the present study, we hypothesized that fibrin is an inducer of
      tissue factor (TF) expression in vascular endothelial cells in vitro and in vivo.
      METHODS AND RESULTS: To test the in vitro aspect of this hypothesis, human
      umbilical vein endothelial cells (HUVECs) were cocultured with physiologically
      relevant concentrations of fibrin (0.03 to 1.0 mg fibrin/mL) for various times
      (0.5 to 24 hours), and TF expression was compared with that in unstimulated
      HUVECs (media control). Results demonstrated that fibrin induced a time- and dose
      dependent increase in TF antigen expression, functional TF procoagulant activity,
      and TF mRNA in HUVECs. CONCLUSIONS: These studies demonstrate that fibrin can
      directly regulate TF expression in HUVECs in vitro.

PMID- 9244234
TI  - Lactate and PO2 modulate superoxide anion production in bovine cardiac myocytes:
      potential role of NADH oxidase.
AB  - BACKGROUND: Lactate increases lucigenin chemiluminescence (CL)-detectable
      superoxide anion (O2.-) generation in bovine vascular smooth muscle and
      endothelium, and a microsomal flavoprotein-containing NADH oxidase whose activity
      is regulated by PO2 and cytosolic NAD(H) redox appears to be the detected source
      of O2.- production. Little is known about the importance of this O2.(-)-producing
      system in cardiac myocytes. METHODS AND RESULTS: In isolated bovine cardiac
      myocytes, lactate (10 mmol/L) increased lucigenin-detectable O2.- levels to
      approximately 1.8 times baseline, whereas pyruvate (10 mmol/L) and mitochondrial
      probes did not increase the detection of O2.-. A nonmitochondrial NADH oxidase
      activity, found in microsomes containing a cytochrome b558, was a major source of
      O2.- production in the homogenate of myocytes, because NADH (0.1 mmol/L)
      increased basal lucigenin CL >100-fold. NADPH oxidases, mitochondria, and
      xanthine oxidase were minor sources of detectable O2.- production. However,
      mitochondria released H2O2 in the presence of 5 mmol/L succinate and 30
      micromol/L antimycin, based on its detection as catalase-inhibitable luminol
      (+horseradish peroxidase)-elicited CL. Diphenyliodonium (DPI), an inhibitor of
      flavoprotein-containing oxidases, significantly attenuated basal, lactate, and
      NADH-elicited lucigenin CL. Hypoxia eliminated myocyte lucigenin CL, and
      posthypoxic reoxygenation caused an 8.6-fold increase in the detection of O2.-
      that was potentiated by lactate and inhibited by DPI. CONCLUSIONS: NADH oxidase
      activity linked to cytosolic NAD(H) redox appears to be a key source of O2.-
      production in cardiac myocytes that could contribute to oxidant signaling
      mechanisms and injury upon exposure to changes in PO2 and metabolites produced
      under hypoxia, such as lactate. These processes could contribute to the
      previously observed potentiation of injury caused by lactate in cardiac
      ischemia/reperfusion.

PMID- 9244235
TI  - Inhibition of vascular smooth muscle cell proliferation and neointimal
      accumulation by adenovirus-mediated gene transfer of cytosine deaminase.
AB  - BACKGROUND: Restenosis remains a significant problem after balloon angioplasty.
      Previous studies have demonstrated that recombinant adenoviruses are efficient
      vectors for gene transfer to the arterial wall and can be used to inhibit the
      proliferative aspect of restenosis. We sought to extend these observations using
      AdCMV.CD, an adenovirus that encodes cytosine deaminase (CD) and is capable of
      metabolizing 5-fluorocytosine (5-FC) to 5-fluorouracil. METHODS AND RESULTS:
      Infection of vascular smooth muscle cells (VSMC) with AdCMV.CD increases by two
      to three orders of magnitude the growth-inhibitory effects of 5-FC. The degree of
      VSMC inhibition in vitro was a function of 5-FC concentration and the level of CD
      expression. Cells infected with AdCMV.CD exhibited a profound bystander effect on
      the growth of neighboring cells, which did not require direct cell-to-cell
      contact. The predominant effect of AdCMV.CD on growth of VSMC appeared to be
      cytostatic, not cytotoxic. Assessment of this strategy in a rabbit femoral artery
      model of balloon-induced injury demonstrated that compared with animals in either
      of two control groups, animals treated with the active combination of infection
      with AdCMV.CD and 1-week treatment with parenteral 5-FC had a significant
      reduction at 30 days in the neointimal-to-medial ratio. CONCLUSIONS: Our results
      suggest that adenovirus-mediated gene transfer of CD along with 5-FC
      administration may be a useful strategy to treat the proliferative aspects of
      restenosis.

PMID- 9244236
TI  - Downregulation of cyclin G1 expression by retrovirus-mediated antisense gene
      transfer inhibits vascular smooth muscle cell proliferation and neointima
      formation.
AB  - BACKGROUND: The contemporary treatment of coronary athero-occlusive disease by
      percutaneous transluminal coronary angioplasty is hampered by maladaptive wound
      healing, resulting in significant failure rates. Morbid sequelae include smooth
      muscle cell (SMC) hyperplasia and restenosis due to vascular neointima formation.
      METHODS AND RESULTS: In this study, we examined the inhibitory effects of a
      concentrated retroviral vector bearing an antisense cyclin G1 gene on aortic SMC
      proliferation in vitro and on neointima formation in vivo in a rat carotid injury
      model of restenosis. Retroviral vectors bearing an antisense cyclin G1 construct
      inhibited the proliferation of transduced aortic SMCs in 2- to 6-day cultures,
      concomitant with down-regulation of cyclin G1 protein expression and decreased
      [3H]thymidine incorporation into DNA. Morphological examination showed evidence
      of cytolysis, giant syncytia formation, and apoptotic changes evidenced by overt
      cell shrinkage, nuclear fragmentation, and specific immunostaining of nascent 3'
      OH DNA ends generated by endonuclease-mediated DNA fragmentation. Pronounced
      "bystander effects" including neighboring cells were noted in aortic SMCs
      transduced with the antisense cyclin G1 vector, as determined by quantitative
      assays and fluorescent labeling of nontransduced cells. In an in vitro tissue
      injury model, the proliferation and migration of antisense cyclin G1 vector
      transduced aortic SMCs were inhibited. Moreover, in vivo delivery of high-titer
      antisense cyclin G1 vector supernatant to the balloon-injured rat carotid artery
      in vivo resulted in a significant reduction in neointima formation. CONCLUSIONS:
      These findings represent the first demonstration of the inhibitory effects of an
      antisense cyclin G1 retroviral vector on nonneoplastic cell proliferation. Taken
      together, these data affirm the potential utility of antisense cyclin G1
      constructs in the development of novel gene therapy approaches to vascular
      restenosis.

PMID- 9244237
TI  - Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in
      vitro and in vivo using local drug delivery.
AB  - BACKGROUND: The antineoplastic compound paclitaxel (Taxol) causes an increased
      assembly of extraordinarily stable microtubules. The present study was designed
      to characterize the effects of paclitaxel on proliferation and migration of human
      arterial smooth muscle cells (haSMCs) in vitro and on neointima formation in an
      in vivo experimental rabbit model. METHODS AND RESULTS: Both monocultures of
      haSMCs and cocultures with human arterial endothelial cells (haECs) were used.
      Cell growth after 4, 8, and 14 days was determined in the absence or presence of
      platelet-derived growth factor-AB (PDGF-AB), basic fibroblast growth factor
      (bFGF), or thrombin. Nonstop paclitaxel exposure, as well as single-dose
      applications of paclitaxel for 24 hours or even 20 minutes (0.1 to 10.0
      micromol/L), caused a complete and prolonged inhibition of haSMC growth up to day
      14, with an IC50 of 2.0 nmol/L. Mitogens or cocultures with stimulating haECs did
      not significantly attenuate paclitaxel-induced effects. Immunohistochemistry
      showed characteristic cytoskeletal changes predominantly in the microtubule
      network. Additionally, in 20 male New Zealand White rabbits, intimal plaques were
      produced by electrical stimulation. In 10 animals, paclitaxel was locally applied
      by use of microporous balloons. Histologically, the intima wall area, wall
      thickness, and degree of stenosis were reduced significantly in paclitaxel
      treated animals compared with controls. CONCLUSIONS: Our data show that
      paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner
      in monocultures and cocultures even in the presence of mitogens. Furthermore,
      paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The
      long-lasting effect after just several minutes' exposure time makes this
      lipophilic substance a promising candidate for local antiproliferative therapy of
      restenosis.

PMID- 9244240
TI  - Infarct size, myocardial hemorrhage, and recovery of function after mechanical
      versus pharmacological reperfusion: effects of lytic state and occlusion time.
AB  - BACKGROUND: Whether myocardial reperfusion obtained with thrombolysis or primary
      angioplasty is associated with a similar recovery of function and with the same
      risk of hemorrhagic infarction is unknown. We evaluated the effects of mechanical
      and pharmacological reperfusion (with or without a plasma lytic state) on infarct
      size, myocardial hemorrhage, and left ventricular (LV) function in a canine
      model. METHODS AND RESULTS: Six groups of six dogs were subjected to balloon
      occlusion of the left anterior descending coronary artery (LAD) followed by 2
      hours of reperfusion. The study had a two-by-three factorial design with two
      occlusion periods (90 and 240 minutes) and three different reperfusion strategies
      (placebo, 0.4 mg/kg recombinant tissue plasminogen activator, and 40 microg/kg
      recombinant staphylokinase). In a seventh control group, LAD occlusion was
      maintained without reperfusion. All dogs received aspirin and heparin. A systemic
      lytic state was present in staphylokinase-treated dogs. Planimetry of LV slices
      showed larger infarcts (percent of area at risk) and more hemorrhage (percent of
      IA) after 240 minutes of occlusion than after 90 minutes of occlusion (54+/-17%
      versus 37+/-18% and 52+/-27% versus 29+/-27%, respectively; P<.01 for both
      comparisons), with no significant difference among treatments. Hemorrhage was not
      observed in the control group without reperfusion. LV angiography showed no
      differences in global and regional LV function between mechanical and
      pharmacological reperfusion. CONCLUSIONS: In this experimental model, hemorrhagic
      infarctions of similar extent were observed after both pharmacological and
      mechanical reperfusion. The extent of hemorrhage was increased by the delay in
      reperfusion but not by the presence of a lytic state.

PMID- 9244238
TI  - Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis
      after balloon-induced arterial injury in minipigs.
AB  - BACKGROUND: Exposure and upregulation of tissue factor in the wall of balloon
      injured arteries may result in prolonged activation of coagulation contributing
      to restenosis. This study was designed to determine whether brief or more
      prolonged inhibition of tissue factor-mediated coagulation with tissue factor
      pathway inhibitor (TFPI) attenuates neointimal formation and luminal stenosis
      after balloon-induced arterial injury. METHODS AND RESULTS: The carotid artery of
      minipigs fed an atherogenic diet was injured by repetitive balloon
      hyperinflations, a procedure that rapidly yields complex, plaque-like neointimal
      lesions and high-grade luminal stenosis. Recombinant TFPI (rTFPI) was
      administered intravenously beginning 15 minutes before balloon injury as either a
      high dose (0.5 mg/kg bolus and 100 microg x kg(-1) x min(-1)) for 3 hours (n=7)
      or 24 hours (n=6) or as a low dose (0.5 mg/kg and 25 microg x kg(-1) x min(-1))
      for 24 hours (n=6). Control animals received intravenous heparin (100 U x kg(-1)
      x h(-1)) for 3 hours (n=6) or 24 hours (n=7) or aspirin (5 mg/kg P.O.) followed
      by heparin for 24 hours (n=7). Luminal stenosis, assessed histologically 4 weeks
      after injury, was 73+/-17% and 76+/-18% (mean+/-SEM) in animals that received
      rTFPI or heparin for 3 hours, respectively. In contrast, luminal stenosis was
      only 11+/-12% and 6+/-3% in pigs given high and low doses, respectively, of rTFPI
      for 24 hours compared with 46+/-22% in pigs given heparin for 24 hours and 40+/
      19% in those given both heparin and aspirin (P<.0002). CONCLUSIONS: Inhibition of
      tissue factor-mediated coagulation during the first 24 hours after deep arterial
      injury appears to be particularly effective for attenuating subsequent neointimal
      formation and stenosis.

PMID- 9244239
TI  - Acute ischemic ventricular arrhythmias in pigs with healed myocardial infarction:
      comparative effects of ischemia at a distance and ischemia at the infarct zone.
AB  - BACKGROUND: The myocardium bordering a healed infarction undergoes
      electrophysiological and autonomic neural derangements that may interact with a
      new ischemic episode to promote arrhythmias. Therefore, peri-infarction ischemia
      may be more arrhythmogenic than ischemia at a distance from the infarct zone, but
      this is not known. METHODS AND RESULTS: Forty-two anesthetized open-chest pigs
      with a 1-month-old myocardial infarction induced by permanent ligature of the
      distal left anterior descending coronary artery (LAD) underwent a coronary
      reocclusion at either the proximal LAD (group 1, peri-infarction ischemia, n=21)
      or at the circumflex coronary artery (group 2, ischemia at a distance, n=21).
      Ventricular arrhythmias were analyzed during 60 minutes of coronary reocclusion
      and during programmed electrical stimulation. Infarct size was measured, and
      underperfusion at the occluded area was estimated by recording 99mTc-tetrofosmin
      activity. Weights of acute ischemic (23+/-9 versus 21+/-9 g) and healed
      infarction (10+/-6 versus 10+/-3 g), baseline LV pressure and peak of LV dP/dt,
      and radiotracer activity at the occluded area (3+/-2% versus 5+/-2% of normal
      tissue) were comparable between the two groups. Compared with group 2, group 1
      showed more ventricular premature beats (median, 136 versus 59; P=.008), a higher
      incidence of spontaneous sustained ventricular tachycardia (57% versus 19%,
      P=.02) and ventricular fibrillation (76% versus 47%, P=.05), and greater
      electrical inducibility of sustained ventricular tachycardia (65% versus 28%,
      P=.03) but comparable induction of ventricular fibrillation. CONCLUSIONS:
      Ischemia superimposed at the border of a 1-month-old myocardial infarction is
      more arrhythmogenic than ischemia at a distance from the infarct zone in swine.
      Data suggest the presence of electrophysiological instability at the peri
      infarction zone.

PMID- 9244241
TI  - L-arginine treatment alters the kinetics of nitric oxide and superoxide release
      and reduces ischemia/reperfusion injury in skeletal muscle.
AB  - BACKGROUND: Constitutive nitric oxide synthase (cNOS) may produce species
      involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient L
      arginine and superoxide at the diminished local L-arginine concentration
      accompanying I/R. METHODS AND RESULTS: During hindlimb I/R (2.5 hours/2 hours),
      in vivo NO was continuously monitored (porphyrinic sensor), and L-arginine
      (chromatography), superoxide (chemiluminescence), and I/R injury were measured
      intermittently. Normal rabbits were compared with those infused with L-arginine 4
      mg x kg(-1) x min(-1) for 1 hour. In both groups, approximately 6 minutes into
      ischemia, a rapid increase of NO from its basal level of 50+/-17 to 115+/-7
      nmol/L, P<.005 (microvessels), was observed. In animals not treated with L
      arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during
      reperfusion. In animals treated with L-arginine, the decrease of NO was slower,
      such that substantial amounts accumulated during reperfusion (25 nmol/L).
      Decreased NO during I/R was accompanied by increased superoxide, which during
      reperfusion reached 50 nmol/L without or 23 nmol/L with L-arginine treatment.
      Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by
      L-NMMA and 25% by L-NAME) during I/R. CONCLUSIONS: L-Arginine treatment decreased
      superoxide generation by cNOS while increasing NO accumulation, leading to
      protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21
      microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber
      area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).

PMID- 9244242
TI  - Glycogen metabolism in the aerobic hypertrophied rat heart.
AB  - BACKGROUND: Rates of glycolysis from exogenous glucose are accelerated in
      hypertrophied hearts. In this study, we determined whether alterations in the
      metabolism of glycogen, an endogenous storage form of glucose, also occur in
      hypertrophied hearts. METHODS AND RESULTS: Rates of glycolysis ([3H]H2O
      production) and oxidation ([14C]CO2 production) from exogenous glucose and
      glycogen were measured in isolated working hearts from control and aortic-banded
      rats. Hearts in which glycogen was prelabeled with [5-(3)H]- or [U-(14)C]glucose
      were perfused with buffer containing 11 mmol/L [5-(3)H]- or [U-(14)C]glucose
      (different from the isotope used to prelabel glycogen), 0.4 mmol/L palmitate, 0.5
      mmol/L lactate, and 100 microU/mL insulin. Rates of glycolysis from exogenous
      glucose were greater (3471+/-114 versus 2665+/-194 nmol glucose x min(-1) x g dry
      wt(-1), P<.05, n=4 to 6, mean+/-SEM) and rates of exogenous glucose oxidation
      (445+/-36 versus 619+/-16 nmol glucose x min(-1) x g dry wt(-1), P<.05, n=4 to 6)
      were lower in hypertrophied hearts than in control hearts. Rates of glycolysis
      and oxidation from glycogen were not different between hypertrophied and control
      hearts. A greater proportion of glycogen was oxidized (80% to 100%) than the
      proportion of exogenous glucose oxidized (13% to 24%) in both groups.
      Additionally, 10.5+/-1.4 and 12.3+/-1.0 micromol/g dry wt of glycogen was
      synthesized in hypertrophied and control hearts, respectively, indicating that
      simultaneous synthesis and degradation (ie, glycogen turnover) occurred in both
      groups. CONCLUSIONS: Thus, aerobic myocardial glycogen metabolism in the
      hypertrophied heart is similar to that observed in the normal heart even though
      exogenous glucose metabolism is altered in the hypertrophied heart.

PMID- 9244243
TI  - High-energy defibrillation increases the severity of postresuscitation myocardial
      dysfunction.
AB  - BACKGROUND: The fatal outcome of victims after initially successful resuscitation
      from cardiac arrest has been attributed both to global myocardial ischemia during
      the interval of cardiac arrest and to the adverse effects of reperfusion. The
      present study was prompted by earlier experimental observation that the magnitude
      of myocardial dysfunction was in part related to the energy delivered during
      electrical defibrillation. METHODS AND RESULTS: Ventricular fibrillation (VF) was
      induced in 15 Sprague-Dawley rats. Precordial compression was begun together with
      mechanical ventilation after 4 minutes of untreated VF and continued for 6
      minutes. Spontaneous circulation was restored in each animal after external
      defibrillation with a single stored 2-, 10-, or 20-J countershock. Cardiac index
      and the rate of left ventricular pressure rise at left ventricular pressure of 40
      mm Hg (dP/dt40) and fall (negative dP/dt) during the 240-minute interval after
      successful resuscitation were decreased, and left ventricular diastolic pressure
      was increased. These decreases in myocardial function were closely related to the
      energy of electrical defibrillation. After a 20-J shock, animals survived for
      only 5+/-3 hours; after a 10-J shock, animals survived for 15+/-4 hours; and
      after a 2-J shock, all animals survived for >24 hours. CONCLUSIONS: The severity
      of postresuscitation myocardial dysfunction is related, at least in part, to the
      magnitude of the electrical energy of the delivered shock.

PMID- 9244244
TI  - Prolonged administration of L-arginine ameliorates chronic pulmonary hypertension
      and pulmonary vascular remodeling in rats.
AB  - BACKGROUND: Endothelium-dependent nitric oxide-mediated vasodilation is impaired
      in rats with pulmonary hypertension (PH) induced by chronic hypoxia or by
      monocrotaline injection. We therefore investigated whether the prolonged
      administration of the nitric oxide precursor L-arginine would alleviate PH in
      both rat models. METHODS AND RESULTS: Fifty-nine rats were exposed to hypobaric
      hypoxia (380 mm Hg, 10 days) or room air and injected intraperitoneally with L
      arginine (500 mg/kg), D-arginine (500 mg/kg), or saline once daily from day -3 to
      day 10. An additional 38 rats injected subcutaneously with monocrotaline (60
      mg/kg) or saline were treated similarly with L-arginine or saline from day -3 to
      day 17. At the end of the experiment, awake mean pulmonary arterial pressure was
      determined. The heart was dissected to weigh the right ventricle, and the lungs
      were obtained for vascular morphometric analysis. Hypoxic rats developed PH
      (30.8+/-0.7 versus 19.2+/-0.4 mm Hg in controls; P<.05) and right ventricular
      hypertrophy. Their pulmonary arterial wall thickness and the proportion of
      muscular arteries in the peripheral arteries increased. L-Arginine but not D
      arginine reduced PH (24.8+/-0.7 mm Hg; P<.05), right ventricular hypertrophy, and
      pulmonary vascular disease. Monocrotaline rats developed PH (34.9+/-2.1 versus
      18.8+/-1.2 mm Hg in controls; P<.05), right ventricular hypertrophy, and
      pulmonary vascular disease. Again, L-arginine reduced PH (24.3+/-1.7 mm Hg;
      P<.05), right ventricular hypertrophy, and pulmonary vascular disease.
      CONCLUSIONS: We conclude that L-arginine ameliorated the changes associated with
      PH in rats, perhaps by modifying the endogenous nitric oxide production.

PMID- 9244245
TI  - Images in cardiovascular medicine. Ruptured papillary muscle.

PMID- 9244246
TI  - Images in cardiovascular medicine. Atheroembolic disease in a female patient.

PMID- 9244247
TI  - American Heart Association Prevention Conference IV: prevention and
      rehabilitation of stroke: executive summary.

PMID- 9244248
TI  - The flgE gene of Campylobacter coli is under the control of the alternative sigma
      factor sigma54.
AB  - The flgE gene encoding the flagellar hook protein of Campylobacter coli VC167-T1
      was cloned by immunoscreening of a genomic library constructed in lambdaZAP
      Express. The flgE DNA sequence was 2,553 bp in length and encoded a protein with
      a deduced molecular mass of 90,639 Da. The sequence had significant homology to
      the 5' and 3' sequences of the flgE genes of Helicobacter pylori, Treponema
      phagedenis, and Salmonella typhimurium. Primer extension analysis indicated that
      the VC167 flgE gene is controlled by a sigma54 promoter. PCR analysis showed that
      the flgE gene size and the 5' and 3' DNA sequences were conserved among C. coli
      and C. jejuni strains. Southern hybridization analyses confirmed that there is
      considerable sequence identity among the hook genes of C. coli and C. jejuni but
      that there are also regions within the genes which differ. Mutants of C. coli
      defective in hook production were generated by allele replacement. These mutants
      were nonmotile and lacked flagellar filaments. Analyses of flgE mutants indicated
      that the carboxy terminus of FlgE is necessary for assembly of the hook structure
      but not for secretion of FlgE and that, unlike salmonellae, the lack of flgE
      expression does not result in repression of flagellin expression.

PMID- 9244249
TI  - Cloning and characterization of CSP37, a novel gene encoding a putative membrane
      protein of Candida albicans.
AB  - In the course of an analysis of the functions and assembly of the cell wall of
      Candida albicans, we have cloned and characterized a gene, which we designated
      CSP37 (cell surface protein), encoding a 37-kDa polypeptide which is a membrane
      associated protein. The gene was isolated by immunological screening of a DNA
      library constructed from mycelial cells with a polyclonal serum raised against
      cell walls of this morphology. Analysis of the nucleotide sequence of a
      corresponding genomic DNA fragment revealed a single open reading frame which
      encodes a predicted protein of 321 amino acids with no significant homology to
      others in the databases. Disruption of the CSP37 gene by the method described by
      Fonzi and Irwin (Genetics 134:717-728, 1993) eliminated expression of the Csp37
      protein. The mutant strains showed no apparent defect in cell viability, growth,
      or cell wall assembly but displayed attenuated virulence in systemic infections
      induced in mice and reduced the ability to adhere to polystyrene.

PMID- 9244250
TI  - The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential
      for viability, and a single Leu-to-Pro mutation in a conserved sequence leads to
      thermosensitivity.
AB  - The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate
      diphosphate to isopentenyl diphosphate, the building block of isoprenoids. We
      used the Saccharomyces cerevisiae temperature-sensitive mutant defective for
      mevalonate diphosphate decarboxylase previously described (C. Chambon, V.
      Ladeveve, M. Servouse, L. Blanchard, C. Javelot, B. Vladescu, and F. Karst,
      Lipids 26:633-636, 1991) to characterize the mutated allele. We showed that a
      single change in a conserved amino acid accounts for the temperature-sensitive
      phenotype of the mutant. Complementation experiments were done both in the erg19
      mutated background and in a strain in which the ERG19 gene, which was shown to be
      an essential gene for yeast, was disrupted. Epitope tagging of the wild-type
      mevalonate diphosphate decarboxylase allowed us to isolate the enzyme in an
      active form by a versatile one-step immunoprecipitation procedure. Furthermore,
      during the course of this study, we observed that a high level of expression of
      the wild-type ERG19 gene led to a lower sterol steady-state accumulation compared
      to that of a wild-type strain, suggesting that this enzyme may be a key enzyme in
      mevalonate pathway regulation.

PMID- 9244251
TI  - Involvement of NtcB, a LysR family transcription factor, in nitrite activation of
      the nitrate assimilation operon in the cyanobacterium Synechococcus sp. strain
      PCC 7942.
AB  - Nitrite, either exogenously supplied or endogenously generated by nitrate
      reduction, activates transcription of the nitrate assimilation operon (nirA
      nrtABCD-narB) in Synechococcus sp. strain PCC 7942 cells treated with L
      methionine-DL-sulfoximine (an inhibitor of glutamine synthetase), in which there
      is no negative feedback resulting from fixation of the ammonium generated by
      nitrite reduction (Kikuchi et al., J. Bacteriol. 178:5822-5825, 1996). Other
      transcription units related to nitrogen assimilation, i.e., the nirB-ntcB operon,
      glnA, and ntcA, were not activated by nitrite. Nitrite did not activate nirA
      operon transcription in a mutant with a deletion of ntcB, an ammonium-repressible
      gene encoding a LysR-type DNA-binding protein. Introduction of plasmid-borne ntcB
      into the ntcB deletion mutant restored the response of the cells to nitrite,
      indicating that NtcB activates the nirA operon in response to nitrite.
      Supplementation of nitrite or nitrate to nitrogen-starved cultures of the wild
      type strain, but not of the ntcB deletion mutant, caused activation of the nirA
      operon without L-methionine-DL-sulfoximine treatment of the cells. The results
      suggested that the positive-regulation mechanism of nirA operon transcription
      plays a role in rapid adaptation of nitrogen-starved cells to changing
      availability of nitrate and nitrite.

PMID- 9244252
TI  - Identification and characterization of an operon of Helicobacter pylori that is
      involved in motility and stress adaptation.
AB  - We identified a novel stress-responsive operon (sro) of Helicobacter pylori that
      contains seven genes which are likely to be involved in cellular functions as
      diverse as chemotaxis, heat shock response, ion transport, and posttranslational
      protein modification. The products of three of these genes show amino acid
      homologies to known proteins, such as the flagellar motor switch protein CheY, a
      class of heat shock proteins, and the ribosomal protein L11 methyltransferase,
      and to a phosphatidyltransferase. In addition to containing an open reading frame
      of unknown function, the product of which is predicted to be membrane associated,
      the sro locus contains three open reading frames that have previously been
      described as constituting two separate loci, the ftsH gene and the copAP operon
      of H. pylori. Knockout mutants showed that CheY is essential for bacterial
      motility and that CopA, but not CopP, relieves copper toxicity. Transcriptional
      analyses indicated that this locus is regulated by a single promoter and that a
      positive effect on transcription is exerted by the addition of copper to the
      medium and by temperature upshift from 37 to 45 degrees C. The possible role of
      this locus in H. pylori virulence is discussed.

PMID- 9244253
TI  - Presence of UDP-N-acetylmuramyl-hexapeptides and -heptapeptides in enterococci
      and staphylococci after treatment with ramoplanin, tunicamycin, or vancomycin.
AB  - Analyses of the peptidoglycan nucleotide precursor contents of enterococci and
      staphylococci treated with ramoplanin, tunicamycin, or vancomycin were carried
      out by high-pressure liquid chromatography coupled with mass spectrometry (MS).
      In all cases, a sharp increase in the UDP-N-actetylmuramoyl-pentapeptide or 
      pentadepsipeptide pool was observed. Concomitantly, new peptidoglycan nucleotide
      peptides of higher molecular masses with hexa- or heptapeptide moieties were
      identified: UDP-MurNAc-pentapeptide-Asp or pentadepsipeptide-Asp in enterococci
      and UDP-MurNAc-pentapeptide-Gly or -Ala and UDP-MurNAc-pentapeptide-Gly-Gly or 
      Ala-Gly in staphylococci. These new compounds are derivatives of normal UDP
      MurNAc-pentapeptide or -pentadepsipeptide precursors with the extra amino acid(s)
      linked to the lysine epsilon-amino group as established by various analytical
      procedures (MS, MS-MS fragmentation, chemical analysis, and digestion with R39
      D,D carboxypeptidase). Except for tunicamycin-treated cells, it was not possible
      to ascertain whether these unusual nucleotides were formed by direct addition of
      the amino acids to UDP-MurNAc-pentapeptide (or -pentadepsipeptide) or whether
      they arose by reverse reactions from lipid I intermediates to which the amino
      acids had been added.

PMID- 9244254
TI  - Characterization of a gene cluster for glycogen biosynthesis and a
      heterotetrameric ADP-glucose pyrophosphorylase from Bacillus stearothermophilus.
AB  - A chromosomal region of Bacillus stearothermophilus TRBE14 which contains genes
      for glycogen synthesis was cloned and sequenced. This region includes five open
      reading frames (glgBCDAP). It has already been demonstrated that glgB encodes
      branching enzyme (EC 2.4.1.18 [H. Takata et al., Appl. Environ. Microbiol.
      60:3096-3104, 1994]). The putative GlgC (387 amino acids [aa]) and GlgD (343 aa)
      proteins are homologous to bacterial ADP-glucose pyrophosphorylase (AGP [EC
      2.7.7.27]): the sequences share 42 to 70% and 20 to 30% identities with AGP,
      respectively. Purification of GlgC and GlgD indicated that AGP is an alpha2beta2
      type heterotetrameric enzyme consisting of these two proteins. AGP did not seem
      to be an allosteric enzyme, although the activities of most bacterial AGPs are
      known to be allosterically controlled. GlgC protein had AGP activity without GlgD
      protein, but its activity was lower than that of the heterotetrameric enzyme. The
      GlgA (485 aa) and GlgP (798 aa) proteins were shown to be glycogen synthase (EC
      2.4.1.21) and glycogen phosphorylase (EC 2.4.1.1), respectively. We constructed
      plasmids harboring these five genes (glgBCDAP) and assayed glycogen production by
      a strain carrying each of the derivative plasmids on which the genes were mutated
      one by one. Glycogen metabolism in B. stearothermophilus is discussed on the
      basis of these results.

PMID- 9244255
TI  - Adaptation of metabolic enzyme activities of Trypanosoma brucei promastigotes to
      growth rate and carbon regimen.
AB  - The insect stage of Trypanosoma brucei adapted the activities of 16 metabolic
      enzymes to growth rate and carbon source. Cells were grown in chemostats with
      glucose, rate limiting or in excess, or high concentrations of proline as carbon
      and energy sources. At each steady state, samples were collected for measurements
      of substrate and end product concentrations, cellular parameters, and enzyme
      activities. Correlation coefficients were calculated for all parameters and used
      to analyze the data set. Rates of substrate consumption and end product formation
      increased with increasing growth rate. Acetate and succinate were the major
      nonvolatile end products, but measurable quantities of alanine were also
      produced. More acetate than succinate was formed during growth on glucose, but
      growth on proline yielded an equimolar ratio. Growth rate barely affected the
      relative amounts of end products formed. The end products accounted for the
      glucose consumed during glucose-limited growth and growth at high rates on excess
      glucose. A discrepancy, indicating production of CO2, occurred during slow growth
      on excess glucose and, even more pronounced, in cells growing on proline. The
      activities of the metabolic enzymes varied by factors of 2 to 40. There was no
      single enzyme that correlated with consumption of substrate and/or end product
      formation in all cases. A group of enzymes whose activities rigorously covaried
      could also not be identified. These findings indicate that T. brucei adapted the
      activities of each of the metabolic enzymes studied separately. The results of
      this complex manner of adaptation were more or less constant ratios of the end
      products and a very efficient energy metabolism.

PMID- 9244256
TI  - A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which
      persists intracellularly.
AB  - Although small-colony variants (SCVs) of Staphylococcus aureus have been
      recognized for many years, this phenotype has only recently been related to
      persistent and recurrent infections. Clinical S. aureus SCVs are frequently
      auxotrophic for menadione or hemin, two compounds involved in the biosynthesis of
      the electron transport chain elements menaquinone and cytochromes, respectively.
      While this observation as well as other biochemical characteristics of SCVs
      suggests a link between electron-transport-defective strains and persistent
      infections, the strains examined thus far have been genetically undefined SCVs.
      Therefore, we generated a stable mutant in electron transport by interrupting one
      of the hemin biosynthetic genes, hemB, in S. aureus by inserting an ermB cassette
      into hemB. We isolated a hemB mutant, due to homologous recombination, by growth
      at a nonpermissive temperature and selection for erythromycin resistance. This
      mutant showed typical characteristics of clinical SCVs, such as slow growth,
      decreased pigment formation, low coagulase activity, reduced hemolytic activity,
      and resistance to aminoglycosides. Additionally, the mutant was able to persist
      within cultured endothelial cells due to decreased alpha-toxin production.
      Northern and Western blot analyses showed that expression of alpha-toxin and that
      of protein A were markedly reduced, at both the mRNA and the protein level. The
      SCV phenotype of the hemB mutant was reversed by growth with hemin or by
      complementation with intact hemB. Hence, a defect in the electron transport
      system allows S. aureus SCVs to resist aminoglycosides and persist
      intracellularly.

PMID- 9244257
TI  - Identification and functional characterization of an ABC transport system
      involved in polysaccharide export of A-band lipopolysaccharide in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa coexpresses two distinct lipopolysaccharide (LPS)
      molecules known as A band and B band. B band is the serospecific LPS, while A
      band is the common LPS antigen composed of a D-rhamnose O-polysaccharide region.
      An operon containing eight genes responsible for A-band polysaccharide
      biosynthesis and export has recently been identified and characterized (H. L.
      Rocchetta, L. L. Burrows, J. C. Pacan, and J. S. Lam, unpublished data; H. L.
      Rocchetta, J. C. Pacan, and J. S. Lam, unpublished data). In this study, we
      report the characterization of two genes within the cluster, designated wzm and
      wzt. The Wzm and Wzt proteins have predicted sizes of 29.5 and 47.2 kDa,
      respectively, and are homologous to a number of proteins that comprise ABC (ATP
      binding cassette) transport systems. Wzm is an integral membrane protein with six
      potential membrane-spanning domains, while Wzt is an ATP-binding protein
      containing a highly conserved ATP-binding motif. Chromosomal wzm and wzt mutants
      were generated by using a gene replacement strategy in P. aeruginosa PAO1
      (serotype 05). Western blot analysis and immunoelectron microscopy using A-band-
      and B-band-specific monoclonal antibodies demonstrated that the wzm and wzt
      mutants were able to synthesize A-band polysaccharide, although transport of the
      polymer to the cell surface was inhibited. The inability of the polymer to cross
      the inner membrane resulted in the accumulation of cytoplasmic A-band
      polysaccharide. This A-band polysaccharide is likely linked to a carrier lipid
      molecule with a phenol-labile linkage. Chromosomal mutations in wzm and wzt were
      found to have no effect on B-band LPS synthesis. Rather, immunoelectron
      microscopy revealed that the presence of A-band LPS may influence the arrangement
      of B-band LPS on the cell surface. These results demonstrate that A-band and B
      band O-antigen assembly processes follow two distinct pathways, with the former
      requiring an ABC transport system for cell surface expression.

PMID- 9244258
TI  - Deletion of the Bacillus subtilis isocitrate dehydrogenase gene causes a block at
      stage I of sporulation.
AB  - A Bacillus subtilis mutant with a deletion of citC, the gene encoding isocitrate
      dehydrogenase, the third enzyme of the tricarboxylic acid branch of the Krebs
      cycle, had a greatly reduced ability to sporulate. Analysis of expression of lacZ
      fusions to various sporulation gene promoters revealed that in the citC mutant
      development is probably blocked between stage 0 and stage II. That is, genes
      expressed very early in sporulation, under the direct control of the Spo0A
      transcription factor, were induced normally in the citC mutant. However, genes
      expressed after asymmetric septation (stage II) in wild-type cells were not
      induced in the citC mutant. Analysis of cell morphology by thin-section electron
      microscopy and immunofluorescence microscopy showed that the mutant formed axial
      chromosomal filaments and accumulated rings of FtsZ protein at potential polar
      division sites but failed to form asymmetric division septa, indicating that
      sporulation is blocked at stage I. The growth and sporulation defects of the B.
      subtilis citC mutant were fully overcome by introduction and expression of the
      Escherichia coli icd gene, encoding an isocitrate dehydrogenase similar to the
      enzyme from B. subtilis.

PMID- 9244259
TI  - Assembly of a functional phage PRD1 receptor depends on 11 genes of the IncP
      plasmid mating pair formation complex.
AB  - PRD1, a lipid-containing double-stranded DNA bacteriophage, uses the mating pair
      formation (Mpf) complex encoded by conjugative IncP plasmids as a receptor.
      Functions responsible for conjugative transfer of IncP plasmids are encoded by
      two distinct regions, Tra1 and Tra2. Ten Tra2 region gene products (TrbB to TrbL)
      and one from the Tra1 region (TraF) form the Mpf complex. We carried out a
      mutational analysis of the PRD1 receptor complex proteins by isolating
      spontaneous PRD1-resistant mutants. The mutations were distributed among the trb
      genes in the Tra2 region and accumulated predominantly in three genes, trbC,
      trbE, and trbL. Three of 307 phage-resistant mutants were weakly transfer
      proficient. Mutations causing a phage adsorption-deficient, transfer-positive
      phenotype were analyzed by sequencing.

PMID- 9244260
TI  - A nonswarming mutant of Proteus mirabilis lacks the Lrp global transcriptional
      regulator.
AB  - Proteus swarming is the rapid cyclical population migration across surfaces by
      elongated cells that hyperexpress flagellar and virulence genes. The mini-Tn5
      transposon mutant mns2 was isolated as a tight nonswarming mutant that did not
      elongate or upregulate flagellar and hemolysin genes. Individual cell motility
      was retained but was reduced. The transposon had inserted in the gene encoding
      the global transcriptional regulator Lrp (leucine-responsive regulatory protein),
      expression of which was upregulated in differentiating swarm cells. Swarming was
      restored to the lrp mutant by artificial overexpression of the flhDC flagellar
      regulatory master operon. Lrp may be a key component in generating or relaying
      signals that are required for flagellation and swarming, possibly acting through
      the flhDC operon.

PMID- 9244261
TI  - Location, degree, and direction of DNA bending associated with the Hin
      recombinational enhancer sequence and Fis-enhancer complex.
AB  - The Fis protein of Escherichia coli and Salmonella typhimurium stimulates several
      site-specific DNA recombination reactions, as well as transcription of a number
      of genes. Fis binds to a 15-bp core recognition sequence and induces DNA bending.
      Mutations in Fis which alter its ability to bend DNA have been shown to reduce
      the stimulatory activity of Fis in both site-specific recombination and
      transcription systems. To examine the role of DNA bending in the activity of the
      Fis-recombinational enhancer complex in Hin-mediated site-specific DNA inversion,
      we have determined the locations, degrees, and directions of DNA bends associated
      with the recombinational enhancer and the Fis-enhancer complex. Circular
      permutation assays demonstrated that a sequence-directed DNA bend is associated
      with the Fis binding sites in the proximal and distal domains of the
      recombinational enhancer. Binding of Fis to its core recognition sequence
      significantly increases the degree of DNA bending associated with the proximal
      and distal domains. The degree of DNA bending induced by Fis binding depended on
      the DNA sequences flanking the core Fis binding site, with angles ranging from 42
      to 69 degrees. Phasing analyses indicate that both the sequence-directed and the
      Fis-induced DNA bends associated with the proximal and distal domains face the
      minor groove of the DNA helix at the center of the Fis binding site. The
      positions and directions of DNA bends associated with the Fis-recombinational
      complex support a direct role for Fis-induced DNA bending in assembly of the
      active invertasome.

PMID- 9244262
TI  - Lipase secretion by bacterial hybrid ATP-binding cassette exporters: molecular
      recognition of the LipBCD, PrtDEF, and HasDEF exporters.
AB  - Serratia marcescens secretes several proteins, such as the lipase LipA, the
      metalloprotease PrtA, and the heme-binding protein HasA, which is required for
      heme acquisition, through two N-terminal signal peptide-independent systems that
      are classified as bacterial ATP-binding cassette (ABC) exporters. One is the ABC
      exporter for HasA, consisting of the ABC protein HasD, the membrane fusion
      protein (MFP) HasE, and the outer membrane protein (OMP) HasF. The second,
      composed of LipB (an ABC protein), LipC (an MFP), and LipD (an OMP), promotes
      secretion of LipA and PrtA in Escherichia coli recombinant clones. PrtA, which
      shows homology to the Erwinia chrysanthemi metalloproteases, is efficiently
      secreted by E. coli cells carrying the E. chrysanthemi ABC exporter PrtD (ABC
      protein)-PrtE (MFP)-PrtF (OMP). The existence of distinct systems in this
      bacterium and of various substrates for these systems allowed the study of
      protein secretion by heterologous Has, Lip, and Prt systems and by Has-Lip and
      Lip-Prt hybrid exporters in the genuine host as well as in E. coli. For that
      purpose, lipB-, lipC-, and lipD-deficient mutants were isolated from S.
      marcescens 8000 and their secretion of LipA and PrtA was analyzed. This
      demonstrated that a unique exporter, the Lip apparatus, in S. marcescens secretes
      both LipA and PrtA. Hybrid exporters were tested for secretion of HasA and LipA.
      The LipB-HasE-HasF exporter allowed secretion of LipA but not HasA, showing that
      the ABC protein LipB is responsible for the substrate specificity. LipA, HasA,
      and E. chrysanthemi PrtC were secreted via heterologous exporters and via some
      hybrid exporters. Analysis of secretion via hybrid exporters showed that specific
      interactions occur between MFPs and OMPs in these systems. These genetic
      experiments demonstrated that specific interactions between the ABC protein and
      the MFP are required for the formation of active exporters.

PMID- 9244263
TI  - Topographical and functional investigation of Escherichia coli penicillin-binding
      protein 1b by alanine stretch scanning mutagenesis.
AB  - Penicillin-binding proteins (PBPs) are the targets of beta-lactam antibiotics. We
      have used a systematic five-alanine substitution method (called ASS [alanine
      stretch scanning] mutagenesis) to investigate the functional or structural role
      of various stretches of amino acids in the PBP1b of Escherichia coli. To probe
      the specific activity of each variant, the antibiotic discs assay was used with
      strain QCB1 (delta ponB) in the presence of cefaloridine, which totally inhibits
      the complementing action of PBP1a. This in vivo test has been combined with a
      quick and efficient in vitro test of the penicillin-binding activity of each of
      these variants with fluorescent penicillin. This approach has enabled us to show
      an unexpected role of the N-terminal and C-terminal tails of PBP1b. Moreover, we
      have established the correct position in PBP1b of the SMN motif that, with the
      SXXK and the KTG motifs, constitutes the signature of the penicilloyl serine
      transferases family. Finally, we have shown that the transglycosylase and the
      transpeptidase domains are separated by an inert linker region, where
      substitutions and insertions can be made without hindering the in vivo and in
      vitro activity of the protein.

PMID- 9244264
TI  - Putative evolutionary origin of plasmids carrying the genes involved in leucine
      biosynthesis in Buchnera aphidicola (endosymbiont of aphids).
AB  - An 8.5-kb plasmid encoding genes (leuABCD) involved in leucine biosynthesis and a
      small plasmid of 1.74 kb of yet unknown function were found in the intracellular
      symbiont, Buchnera aphidicola, of two divergent aphid species, Thelaxes suberi
      and Tetraneura caerulescens, respectively. The leuABCD-carrying plasmid (pBTs1)
      was amplified from total aphid DNA by inverse long PCR, using outwardly oriented
      oligonucleotide primers specific to leuA. The resulting 8.2-kb PCR fragment as
      well as the 1.74-kb plasmid (pBTc1) were cloned and sequenced. pBTs1 differed
      from a previously described B. aphidicola plasmid (pRPE) of the aphid
      Rhopalosiphum padi by the presence of a small heat shock gene (ibp) and in the
      order of the leuABCD and repA genes. Comparison of both leucine plasmids to the
      small plasmid pBTc1 revealed extensive similarity with respect to putative
      replication functions as well as in the presence of a highly conserved open
      reading frame that was found to be homologous to Escherichia coli YqhA and
      Haemophilus influenzae HI0507 and which may encode an integral membrane protein.
      The three B. aphidicola plasmids most likely evolved from a common ancestral
      replicon, which in turn may be distantly related to IncFII plasmids. Phylogenetic
      affiliations of the B. aphidicola strains of the two aphid species were assessed
      by sequencing of their 16S rRNA genes. Evaluation of the distribution of the
      leuABCD-encoding plasmids within a phylogenetic framework suggests independent
      origins for pBTs1 and pRPE from an ancestral replicon resembling pBTc1. The
      implications for symbiotic essential amino acid biosynthesis and provisioning are
      discussed.

PMID- 9244265
TI  - The Tla protein of Porphyromonas gingivalis W50: a homolog of the RI protease
      precursor (PrpRI) is an outer membrane receptor required for growth on low levels
      of hemin.
AB  - The prpR1 gene of Porphyromonas gingivalis W50 encodes the polyprotein precursor
      (PrpRI) of an extracellular arginine-specific protease. PrpRI is organized into
      four distinct domains (pro, alpha, beta, and gamma) and is processed to a
      heterodimeric protease (RI) which comprises the alpha and beta components in a
      noncovalent association. The alpha component contains the protease active site,
      whereas the beta component appears to have a role in adherence and
      hemagglutination processes. DNA sequences homologous to the coding region for the
      RI beta component are present at multiple loci on the P. gingivalis chromosome
      and may represent a family of related genes. In this report, we describe the
      cloning, sequence analysis, and characterization of one of these homologous loci
      isolated in plasmid pJM7. The 6,041-bp P. gingivalis DNA fragment in pJM7
      contains a major open reading frame of 3,291 bp with coding potential for a
      protein with an Mr 118,700. An internal region of the deduced sequence (V304 to
      N768) shows 98% identity to the beta domain of PrpRI, and the recombinant product
      of pJM7 is immunoreactive with an antibody specific to the RI beta component. The
      N terminus of the deduced sequence has regional similarity to TonB-linked
      receptors which are frequently involved in periplasmic translocation of hemin,
      iron, colicins, or vitamin B12 in other bacteria. We have therefore designated
      this gene tla (TonB-linked adhesin). In contrast to the parent strain, an
      isogenic mutant of P. gingivalis W50 in which the tla was insertionally
      inactivated was unable to grow in medium containing low concentrations of hemin
      (<2.5 mg liter(-1)), and hemin-depleted cells of this mutant failed to respond to
      hemin in an agar diffusion plate assay. These data suggest a role for this gene
      product in hemin acquisition and utilization. Furthermore, the mutant produced
      significantly less arginine- and lysine-specific protease activities than the
      parent strain, indicating that there may be a regulatory relationship between tla
      and other members of this gene family.

PMID- 9244266
TI  - Cloning and expression in Escherichia coli of genetic determinants for production
      of and immunity to microcin E492 from Klebsiella pneumoniae.
AB  - Microcin E492 is a polypeptide antibiotic that is produced and excreted by
      Klebsiella pneumoniae RYC492. The genetic determinants for microcin synthesis and
      immunity were cloned in Escherichia coli VCS257 into the cosmid vector pHC79,
      starting from total DNA of K. pneumoniae RYC492. The microcin E492 expressed in
      E. coli had the same properties as that of K. pneumoniae, i.e., the same
      molecular weight, the ability to form ionic channels in planar phospholipid
      bilayers, and essentially identical biological properties. Microcin E492
      expression in E. coli, like that in K. pneumoniae, was mainly in the exponential
      phase of growth, declining in the stationary phase. The immunity determinant was
      subcloned into the same vector, and its expression was found to disappear in the
      stationary phase. This phenomenon is not dependent on rpoS, the stationary-phase
      sigma factor.

PMID- 9244267
TI  - Molecular analysis of kanamycin and viomycin resistance in Mycobacterium
      smegmatis by use of the conjugation system.
AB  - We examined the molecular mechanisms of resistance to kanamycin and viomycin in
      Mycobacterium smegmatis. All of the M. smegmatis strains with high-level
      kanamycin resistance had a nucleotide substitution from A to G at position 1389
      of the 16S rRNA gene (rrs). This position is equivalent to position 1408 of
      Escherichia coli, and mutation at this position is known to cause aminoglycoside
      resistance. Mutations from G to A or G to T at position 1473 of the M. smegmatis
      rrs gene were found in viomycin-resistant mutants which had been designated vicB
      mutants in our earlier studies. Using the M. smegmatis conjugation system, we
      confirmed that these mutations indeed contributed to kanamycin and viomycin
      resistance, and kanamycin susceptibility was dominant over resistance in a
      heterogenomic strain. Additional experiments showed that three of four
      Mycobacterium tuberculosis strains with high-level kanamycin resistance had a
      mutation from A to G at position 1400, which was equivalent to position 1389 of
      M. smegmatis.

PMID- 9244268
TI  - Isolation, characterization, and complementation of a motility mutant of
      Spiroplasma citri.
AB  - The helical mollicute Spiroplasma citri, when growing on low-agar medium, forms
      fuzzy colonies with occasional surrounding satellite colonies due to the ability
      of the spiroplasmal cells to move through the agar matrix. In liquid medium,
      these helical organisms flex, twist, and rotate rapidly. By using Tn4001
      insertion mutagenesis, a motility mutant was isolated on the basis of its
      nondiffuse, sharp-edged colonies. Dark-field microscopy observations revealed
      that the organism flexed at a low frequency and had lost the ability to rotate
      about the helix axis. In this mutant, the transposon was shown to be inserted
      into an open reading frame encoding a putative polypeptide of 409 amino acids for
      which no significant homology with known proteins was found. The corresponding
      gene, named scm1, was recovered from the wild-type strain and introduced into the
      motility mutant by using the S. citri oriC plasmid pBOT1 as the vector. The
      appearance of fuzzy colonies and the observation that spiroplasma cells displayed
      rotatory and flexional movements showed the motile phenotype to be restored in
      the spiroplasmal transformants. The functional complementation of the motility
      mutant proves the scm1 gene product to be involved in the motility mechanism of
      S. citri.

PMID- 9244269
TI  - A new Thermus-Escherichia coli shuttle integration vector system.
AB  - We established a Thermus thermophilus strain in which the pyrE gene (coding for
      orotate phosphoribosyltransferase of the pyrimidine biosynthetic pathway) was
      totally deleted. We also constructed an integration vector, which consisted of
      the Escherichia coli plasmid vector pBluescript and a 2.1-kb segment of the T.
      thermophilus leu operon sequence, for the integration of a foreign gene into a
      chromosome of the thermophile. pyrE and leuB genes were used as probes to test
      the integration vector. The integration vector pINV, bearing the pyrE gene,
      transformed the delta pyrE strain at a frequency of 6 x 10(-5) through a single
      crossover event. The leuB gene could also be used as another marker of the
      integration vector system. The vector could be integrated at the expected site.
      By digesting the chromosomal DNA of the T. thermophilus transformants with a
      unique restriction enzyme, the vector could be recovered into E. coli after the
      recircularization in vitro. The kanamycin nucleotidyltransferase gene could be
      successfully expressed in the thermophile by using pINV.

PMID- 9244270
TI  - The Haemophilus influenzae dprABC genes constitute a competence-inducible operon
      that requires the product of the tfoX (sxy) gene for transcriptional activation.
AB  - We previously showed that dprA is required for efficient processing of linear DNA
      during cellular transformation in Haemophilus influenzae. In this study the
      transcriptional regulation of dprA and two downstream genes, dprB and dprC, is
      examined. We demonstrate by Northern blot analysis that the dprABC genes are
      transcriptionally coregulated and competence inducible. We used primer extension
      analysis to map the transcriptional start site of dprA and of rec-2, another
      transformation gene involved in DNA processing. Based upon these results, we were
      able to identify a 26-bp dyad symmetry element immediately upstream of the -35
      regions of the predicted promoters of dprA, rec-2, and two other transformation
      genes, comA and pilA. Finally, using transcriptional fusions of dprA to the
      Escherichia coli lacZ gene, we show that expression of dprA::lacZ requires tfoX
      and that the presence of multiple copies of tfoX abolishes the temporal
      regulation of dprA, resulting in its constitutive expression.

PMID- 9244271
TI  - Cloning and analysis of the poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
      biosynthesis genes of Aeromonas caviae.
AB  - A 5.0-kbp EcoRV-EcoRI restriction fragment was cloned and analyzed from genomic
      DNA of Aeromonas caviae, a bacterium producing a copolyester of (R)-3
      hydroxybutyrate (3HB) and (R)-3-hydroxyhexanoate (3HHx) [P(3HB-co-3HHx)] from
      alkanoic acids or oils. The nucleotide sequence of this region showed a 1,782-bp
      poly (3-hydroxyalkanoate) (PHA) synthase gene (phaC(Ac) [i.e., the phaC gene from
      A. caviae]) together with four open reading frames (ORF1, -3, -4, and -5) and one
      putative promoter region. The cloned fragments could not only complement PHA
      negative mutants of Alcaligenes eutrophus and Pseudomonas putida, but also confer
      the ability to synthesize P(3HB-co-3HHx) from octanoate or hexanoate on the
      mutants' hosts. Furthermore, coexpression of ORF1 and ORF3 genes with phaC(Ac) in
      the A. eutrophus mutant resulted in a decrease in the polyester content of the
      cells. Escherichia coli expressing ORF3 showed (R)-enoyl-coenzyme A (CoA)
      hydratase activity, suggesting that (R)-3-hydroxyacyl-CoA monomer units are
      supplied via the (R)-specific hydration of enoyl-CoA in A. caviae. The
      transconjugant of the A. eutrophus mutant expressing only phaC(Ac) effectively
      accumulated P(3HB-co-3HHx) up to 96 wt% of the cellular dry weight from octanoate
      in one-step cultivation.

PMID- 9244272
TI  - A T-DNA gene required for agropine biosynthesis by transformed plants is
      functionally and evolutionarily related to a Ti plasmid gene required for
      catabolism of agropine by Agrobacterium strains.
AB  - The mechanisms that ensure that Ti plasmid T-DNA genes encoding proteins involved
      in the biosynthesis of opines in crown gall tumors are always matched by Ti
      plasmid genes conferring the ability to catabolize that set of opines on the
      inducing Agrobacterium strains are unknown. The pathway for the biosynthesis of
      the opine agropine is thought to require an enzyme, mannopine cyclase, coded for
      by the ags gene located in the T(R) region of octopine-type Ti plasmids. Extracts
      prepared from agropine-type tumors contained an activity that cyclized mannopine
      to agropine. Tumor cells containing a T region in which ags was mutated lacked
      this activity and did not contain agropine. Expression of ags from the lac
      promoter conferred mannopine-lactonizing activity on Escherichia coli.
      Agrobacterium tumefaciens strains harboring an octopine-type Ti plasmid exhibit a
      similar activity which is not coded for by ags. Analysis of the DNA sequence of
      the gene encoding this activity, called agcA, showed it to be about 60% identical
      to T-DNA ags genes. Relatedness decreased abruptly in the 5' and 3' untranslated
      regions of the genes. ags is preceded by a promoter that functions only in the
      plant. Expression analysis showed that agcA also is preceded by its own promoter,
      which is active in the bacterium. Translation of agcA yielded a protein of about
      45 kDa, consistent with the size predicted from the DNA sequence. Antibodies
      raised against the agcA product cross-reacted with the anabolic enzyme. These
      results indicate that the agropine system arose by a duplication of a progenitor
      gene, one copy of which became associated with the T-DNA and the other copy of
      which remained associated with the bacterium.

PMID- 9244273
TI  - Cloning of genes involved in carbazole degradation of Pseudomonas sp. strain
      CA10: nucleotide sequences of genes and characterization of meta-cleavage enzymes
      and hydrolase.
AB  - The DNA fragment encoding meta-cleavage enzymes and the meta-cleavage compound
      hydrolase, involved in carbazole degradation, was cloned from the carbazole
      utilizing bacterium Pseudomonas sp. strain CA10. DNA sequence analysis of this
      2.6-kb SmaI-SphI fragment revealed that there were three open reading frames
      (ORF1, ORF2, and ORF3, in this gene order). ORF1 and ORF2 were indispensable for
      meta-cleavage activity for 2'-aminobiphenyl-2,3-diol and its easily available
      analog, 2,3-dihydroxybiphenyl, and were designated carBa and carBb, respectively.
      The alignment of CarBb with other meta-cleavage enzymes indicated that CarBb may
      have a non-heme iron cofactor coordinating site. On the basis of the phylogenetic
      tree, CarBb was classified as a member of the protocatechuate 4,5-dioxygenase
      family. This unique extradiol dioxygenase, CarB, had significantly higher
      affinity and about 20-times-higher meta-cleavage activity for 2,3
      dihydroxybiphenyl than for catechol derivatives. The putative polypeptide encoded
      by ORF3 was homologous with meta-cleavage compound hydrolases in other bacteria,
      and ORF3 was designated carC. The hydrolase activity of CarC for 2-hydroxy-6-oxo
      6-phenylhexa-2,4-dienoic acid, the meta-cleavage compound of 2,3
      dihydroxybiphenyl, was 40 times higher than that for 2-hydroxy-6-oxohepta-2,4
      dienoic acid, the meta-cleavage compound of 3-methylcatechol. Alignment analysis
      and the phylogenetic tree indicate that CarC has greatest homologies with
      hydrolases involved in the monoaromatic compound degradation pathway. These
      results suggest the possibility that CarC is a novel type of hydrolase.

PMID- 9244274
TI  - Identification and characterization of genes encoding carbazole 1,9a-dioxygenase
      in Pseudomonas sp. strain CA10.
AB  - Nucleotide sequence analysis of the flanking regions of the carBC genes of
      Pseudomonas sp. strain CA10 revealed that there were two open reading frames
      (ORFs) ORF4 and ORF5, in the upstream region of carBC. Similarly, three ORFs,
      ORF6 to ORF8, were found in the downstream region of carBC. The deduced amino
      acid sequences of ORF6 and ORF8 showed homologies with ferredoxin and ferredoxin
      reductase components of bacterial multicomponent dioxygenase systems,
      respectively. ORF4 and ORF5 had the same sequence and were tandemly linked. Their
      deduced amino acid sequences showed about 30% homology with large (alpha)
      subunits of other terminal oxygenase components. Functional analysis using
      resting cells harboring the deleted plasmids revealed that the products of ORF4
      and -5, ORF6, and ORF8 were terminal dioxygenase, ferredoxin, and ferredoxin
      reductase, respectively, of carbazole 1,9a-dioxygenase (CARDO), which attacks the
      angular position adjacent to the nitrogen atom of carbazole, and that the product
      of ORF7 is not indispensable for CARDO activity. Based on the results, ORF4,
      ORF5, ORF6, and ORF8 were designated carAa, carAa, carAc, and carAd,
      respectively. The products of carAa, carAd, and ORF7 were shown by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis to be polypeptides with molecular
      masses of 43, 36, and 11 kDa, respectively. However, the product of carAc was not
      detected in Escherichia coli. CARDO has the ability to oxidize a wide variety of
      polyaromatic compounds, including dibenzo-p-dioxin, dibenzofuran, biphenyl, and
      polycyclic aromatic hydrocarbons such as naphthalene and phenanthrene. Since
      2,2',3-trihydroxydiphenyl ether and 2,2',3-trihydroxybiphenyl were identified as
      metabolites of dibenzo-p-dioxin and dibenzofuran, respectively, it was considered
      that CARDO attacked at the angular position adjacent to the oxygen atom of
      dibenzo-p-dioxin and dibenzofuran as in the case with carbazole.

PMID- 9244275
TI  - The reductive tricarboxylic acid cycle of carbon dioxide assimilation: initial
      studies and purification of ATP-citrate lyase from the green sulfur bacterium
      Chlorobium tepidum.
AB  - Carbon dioxide is fixed largely by the reductive tricarboxylic acid (RTCA) cycle
      in green sulfur bacteria. One of the key enzymes, ATP-citrate lyase, was purified
      to apparent homogeneity from the moderately thermophilic green sulfur bacterium
      Chlorobium tepidum. The molecular weight of the native enzyme was about 550,000,
      and the preponderance of evidence indicated that the protein is composed of
      identical subunits (Mr of approximately 135,000) which degraded to two major
      proteins with Mrs of approximately 65,000 and approximately 42,000. Western
      immunoblots and in vitro phosphorylation experiments indicated that these two
      species could have been the result of proteolysis by an endogenous protease,
      similar to what has been observed with mammalian, yeast, and mold ATP-citrate
      lyase. In addition to apparent structural similarities, the catalytic properties
      of C. tepidum ATP-citrate lyase showed marked similarities to the eukaryotic
      enzyme, with significant differences from other prokaryotic ATP-citrate lyases,
      including the enzyme from the closely related organism Chlorobium limicola.
      Phosphorylation of C. tepidum ATP-citrate lyase occurred, presumably on a
      histidine residue at the active site, similar to the case for the mammalian
      enzyme. In contrast to the situation observed for other prokaryotic ATP-citrate
      lyase enzymes, the C. tepidum enzyme was not able to replace ATP and GTP for
      activity or use Cu2+ to replace Mg2+ for enzyme activity. Given the apparent
      structural and catalytic similarities of the enzyme from C. tepidum and its
      eukaryotic counterpart, the C. tepidum system should serve as an excellent model
      for studies of the enzymology and regulation of this protein.

PMID- 9244276
TI  - Involvement of Fnr and ArcA in anaerobic expression of the tdc operon of
      Escherichia coli.
AB  - Anaerobic expression of the tdcABC operon in Escherichia coli, as measured by
      LacZ activity from single-copy tdc-lacZ transcriptional and translational
      fusions, is greatly reduced in strains lacking two global transcriptional
      regulators, Fnr and ArcA. The nucleotide sequence of the tdc promoter around -145
      shows significant similarity with the consensus Fnr-binding site; however,
      extensive base substitutions within this region had no effect on Fnr regulation
      of the tdc genes. A genetic analysis revealed that the effect of Fnr on tdc is
      not mediated via ArcA. Furthermore, addition of cyclic AMP to the anaerobic
      incubation medium completely restored tdc expression in fnr and arcA mutants as
      well as in strains harboring mutations in the Fnr- and ArcA-dependent pfl gene
      and the Fnr-regulated glpA and frd genes. These results, taken together with the
      earlier finding that tdc expression is subject to catabolite repression by
      intermediary metabolites, strongly suggest that the negative regulatory effects
      of mutations in the fnr and arcA genes are mediated physiologically due to
      accumulation of a metabolite(s) which prevents tdc transcription in vivo.

PMID- 9244278
TI  - Mutational analysis of the Vibrio fischeri LuxI polypeptide: critical regions of
      an autoinducer synthase.
AB  - Synthesis of the Vibrio fischeri autoinducer, a signal involved in the cell
      density-dependent activation of bioluminescence, is directed by the luxI gene
      product. The LuxI protein catalyzes the synthesis of N-acyl-homoserine lactones
      from S-adenosylmethionine and acylated-acyl carrier protein. We have gained an
      appreciation of the LuxI regions and amino acid residues involved in autoinducer
      synthesis by isolating and analyzing mutations generated by random and site
      specific mutagenesis of luxI. By random mutagenesis we isolated 13 different
      single amino acid substitutions in the LuxI polypeptide. Eleven of these
      substitutions resulted in no detectable autoinducer synthase activity, while the
      remaining two amino acid substitutions resulted in reduced but detectable
      activity. The substitutions that resulted in no detectable autoinducer synthase
      activity mapped to two small regions of LuxI. In Escherichia coli, wild-type luxI
      showed dominance over all of the mutations. Because autoinducer synthesis has
      been proposed to involve formation of a covalent bond between an acyl group and
      an active-site cysteine, we constructed site-directed mutations that altered each
      of the three cysteine residues in LuxI. All of the cysteine mutants retained
      substantial activity as an autoinducer synthase in E. coli. Based on the analysis
      of random mutations we propose a model in which there are two critical regions of
      LuxI, at least one of which is an intimate part of an active site, and based on
      the analysis of site-directed mutations we conclude that an active-site cysteine
      is not essential for autoinducer synthase activity.

PMID- 9244277
TI  - Osmoprotectant-dependent expression of plcH, encoding the hemolytic phospholipase
      C, is subject to novel catabolite repression control in Pseudomonas aeruginosa
      PAO1.
AB  - Expression of the hemolytic phospholipase C (PlcH) of Pseudomonas aeruginosa is
      induced under phosphate starvation conditions or in the presence of the
      osmoprotectants choline and glycine betaine. Because choline and glycine betaine
      may serve as carbon and energy sources in addition to conferring osmoprotection
      to P. aeruginosa, it seemed possible that induction of plcH is subject to
      catabolite repression control (CRC) by tricarboxylic cycle intermediates such as
      succinate. Total phospholipase (PLC) activity in osmoprotectant-induced cultures
      of P. aeruginosa PAO1 supplemented with 20 mM succinate was three- to fourfold
      lower than the levels in cultures supplemented with the non-catabolite-repressive
      substrate lactate. Analyses of osmoprotectant-dependent plcH expression in a
      derivative of strain PAO1 containing a plcH::lacZ operon fusion showed that (i)
      succinate prevented induction of plcH expression by osmoprotectants; and (ii)
      addition of succinate reduced or shut down further expression of plcH in
      osmoprotectant-induced bacteria, while cultures supplemented with lactate had
      little or no change in plcH expression. RNase protection analysis confirmed that
      repression of plcH occurs at the transcriptional level. However, a P. aeruginosa
      mutant decoupled in CRC exhibited a phenotype similar to that of the wild-type
      strain (PAO1) with respect to succinate-dependent repression of plcH expression.
      Osmoprotectant-induced total PLC activities, levels of expression of plcH
      measured with the same plcH::lacZ fusion, and levels of plcH transcription in a
      CRC-deficient strain reflected those seen in strain PAO1. This indicates that CRC
      of plcH functions by a distinct mechanism which differs from that regulating the
      glucose or mannitol catabolic pathway. A strain carrying a mutation in vfr, which
      encodes the Escherichia coli Crp homolog in P. aeruginosa, still exhibited a wild
      type phenotype with respect to osmoprotectant-dependent expression and CRC of
      plcH. These data indicate that there is a novel CRC system that regulates the
      expression of plcH in P. aeruginosa.

PMID- 9244279
TI  - Bacillus subtilis Pro-sigmaE fusion protein localizes to the forespore septum and
      fails to be processed when synthesized in the forespore.
AB  - Endospore formation in Bacillus subtilis begins with an asymmetric cell division
      that partitions the bacterium into mother cell and forespore compartments. Mother
      cell-specific gene expression is initiated by sigmaE, a transcription factor that
      is active only in the mother cell but which existed as an inactive precursor (pro
      sigmaE) in the predivisional cell. Activation of pro-sigmaE involves the removal
      of 27 amino acids from its amino terminus. A chimera of pro-sigmaE and the green
      fluorescent protein (GFP) was expressed from either the normal sigE promoter
      (P(spoIIG)), which places pro-sigmaE::GFP in both mother cell and forespore
      compartments, or the forespore-specific promoter (P(dacF)), which produces pro
      sigmaE::GFP only in the forespore compartment. The pro-sigmaE::GFP expressed from
      P(spoIIG), but not P(dacF), was converted to a lower-molecular-weight form by a
      mechanism dependent on gene products (SpoIIGA and sigmaF) that are essential for
      normal pro-sigmaE processing. This finding is consistent with the pro-sigmaE
      processing reaction occurring only in the mother cell compartment. In processing
      deficient cells, pro-sigmaE::GFP was found to accumulate at the septal membrane,
      a location where its processing apparatus would be susceptible to triggering from
      the adjoining forespore.

PMID- 9244280
TI  - Identification and characterization of an operon in Salmonella typhimurium
      involved in thiamine biosynthesis.
AB  - Thiamine pyrophosphate (TPP) is synthesized de novo in Salmonella typhimurium and
      is a required cofactor for many enzymes in the cell. Five kinase activities have
      been implicated in TPP synthesis, which involves joining a 4-methyl-5-(beta
      hydroxyethyl)thiazole (THZ) moiety and a 4-amino-5-hydroxymethyl-2
      methylpyrimidine (HMP) moiety. We report here identification of a 2-gene operon
      involved in thiamine biosynthesis and present evidence that the genes in this
      operon, thiMD, encode two previously identified kinases, THZ kinase and HMP
      phosphate (HMP-P) kinase, respectively. We further show that this operon belongs
      to the growing class of genes involved in TPP synthesis that are
      transcriptionally regulated by TPP. Our data are consistent with ThiM being a
      salvage enzyme and ThiD being a biosynthetic enzyme involved in TPP synthesis, as
      previously suggested.

PMID- 9244281
TI  - Biochemical characterization of penicillin-resistant and -sensitive penicillin
      binding protein 2x transpeptidase activities of Streptococcus pneumoniae and
      mechanistic implications in bacterial resistance to beta-lactam antibiotics.
AB  - To understand the biochemical basis of resistance of bacteria to beta-lactam
      antibiotics, we purified a penicillin-resistant penicillin-binding protein 2x (R
      PBP2x) and a penicillin-sensitive PBP2x (S-PBP2x) enzyme of Streptococcus
      pneumoniae and characterized their transpeptidase activities, using a thioester
      analog of stem peptides as a substrate. A comparison of the k(cat)/Km values for
      the two purified enzymes (3,400 M(-1) s(-1) for S-PBP2x and 11.2 M(-1) s(-1) for
      R-PBP2x) suggests that they are significantly different kinetically. Implications
      of this finding are discussed. We also found that the two purified enzymes did
      not possess a detectable level of beta-lactam hydrolytic activity. Finally, we
      show that the expression levels of both PBP2x enzymes were similar during
      different growth phases.

PMID- 9244282
TI  - Characterization of the pecT control region from Erwinia chrysanthemi 3937.
AB  - Erwinia chrysanthemi synthesizes and secretes pectate lyases that attack
      components of the plant cell wall and, therefore, play a major role in the
      pathogenesis of soft rot disease. We isolated a new mutant (designated pec-1), by
      Tn5 mutagenesis, that displays weak pectate lyase production and decreased
      motility and mucoidicity. Maceration and pathogenicity tests done on different
      plant organs showed that the pec-1 strain displays a reduced virulence compared
      to that of the parental strain. The Tn5 insertion was localized between the pelL
      and the out loci and defines a new regulatory region. Sequencing of the pec
      1::Tn5 insertion revealed that pec-1 is tightly linked to the pecT regulatory
      gene that also controls pectate lyase synthesis. Moreover, the pecT mutation is
      dominant over the pec-1 mutation, suggesting that these two loci are involved in
      the same regulatory network. We demonstrated, by Northern blot analysis, that the
      pec-1::Tn5 insertion provokes derepression of pecT transcription and defines a
      cis-acting element. Introduction of the pecT gene in trans of a pecT::uidA fusion
      induced a decrease of pecT::uidA transcription, indicating a negative
      autoregulation. Band shift experiments confirmed that the PecT repressor
      specifically interacts with the pecT regulatory region. We also demonstrated that
      the PecT protein interacts with the regulatory region of the pelD gene encoding a
      pectate lyase. Therefore, the abolition of the pecT autoregulation in the pec-1
      mutant provokes an overproduction of the PecT repressor that is responsible for
      the decrease of pectate lyase synthesis. Mutagenesis of the pecT regulatory
      region revealed the presence of two sites in which insertions reproduced the pec
      1 phenotype. This result suggests that pecT autoregulation requires the presence
      of two functional operator sites. From this study, we propose that the PecT
      repressor binds to these two sites, generating a loop that blocks pecT
      transcription.

PMID- 9244283
TI  - Colicin U, a novel colicin produced by Shigella boydii.
AB  - A novel colicin, designated colicin U, was found in two Shigella boydii strains
      of serovars 1 and 8. Colicin U was active against bacterial strains of the genera
      Escherichia and Shigella. Plasmid pColU (7.3 kb) of the colicinogenic strain S.
      boydii M592 (serovar 8) was sequenced, and three colicin genes were identified.
      The colicin U activity gene, cua, encodes a protein of 619 amino acids (Mr,
      66,289); the immunity gene, cui, encodes a protein of 174 amino acids (Mr,
      20,688); and the lytic protein gene, cul, encodes a polypeptide of 45 amino acids
      (Mr, 4,672). Colicin U displays sequence similarities to various colicins. The N
      terminal sequence of 130 amino acids has 54% identity to the N-terminal sequence
      of bacteriocin 28b produced by Serratia marcescens. Furthermore, the N-terminal
      36 amino acids have striking sequence identity (83%) to colicin A. Although the C
      terminal pore-forming sequence of colicin U shows the highest degree of identity
      (73%) to the pore-forming C-terminal sequence of colicin B, the immunity protein,
      which interacts with the same region, displays a higher degree of sequence
      similarity to the immunity protein of colicin A (45%) than to the immunity
      protein of colicin B (30.5%). Immunity specificity is probably conferred by a
      short sequence from residues 571 to residue 599 of colicin U; this sequence is
      not similar to that of colicin B. We showed that binding of colicin U to
      sensitive cells is mediated by the OmpA protein, the OmpF porin, and core
      lipopolysaccharide. Uptake of colicin U was dependent on the TolA, -B, -Q, and -R
      proteins. pColU is homologous to plasmid pSB41 (4.1 kb) except for the colicin
      genes on pColU. pSB41 and pColU coexist in S. boydii strains and can be
      cotransformed into Escherichia coli, and both plasmids are homologous to pColE1.

PMID- 9244284
TI  - Localization and cell surface anchoring of the Saccharomyces cerevisiae
      flocculation protein Flo1p.
AB  - The Saccharomyces cerevisiae FLO1 gene encodes a large 1,536-amino-acid serine-
      and threonine-rich protein involved in flocculation. We have assessed the
      localization of Flo1p by immunoelectron microscopy, and in this study we show
      that this protein is located in the external mannoprotein layer of the cell wall,
      at the plasma membrane level and in the periplasm. The protein was also
      visualized in the endoplasmic reticulum and in the nuclear envelope, indicating
      that it was secreted through the secretory pathway. The protein was detected by
      Western blotting in cell wall extracts as a high-molecular-mass (>200 kDa)
      polydisperse material obviously as a result of extensive N and probably O
      glycosylation. Flo1p was extracted from cell walls in large amounts by boiling in
      sodium dodecyl sulfate, suggesting that it is noncovalently anchored to the cell
      wall network. The membranous forms of Flo1p were shown to be solubilized by
      phosphatidylinositol-phospholipase C treatment, suggesting that Flo1p is glycosyl
      phosphatidylinositol (GPI) anchored to this organelle. The expression of
      truncated forms with the hydrophobic C-terminal domain deleted led to the
      secretion of the protein in the culture medium. The hydrophobic C terminus, which
      is a putative GPI anchoring domain, is therefore necessary for the attachment of
      Flo1p in the cell wall. Deletion analysis also revealed that the N-terminal
      domain of Flo1p was essential for cellular aggregation. On the whole, our data
      indicate that Flo1p is a true cell wall protein which plays a direct role in cell
      cell interaction.

PMID- 9244285
TI  - Cloning and expression of the two genes coding for L-serine dehydratase from
      Peptostreptococcus asaccharolyticus: relationship of the iron-sulfur protein to
      both L-serine dehydratases from Escherichia coli.
AB  - The structural genes sdhA and sdhB, coding for the alpha- and beta-subunits of
      the [4Fe-4S] cluster containing L-serine dehydratase from Peptostreptococcus
      asaccharolyticus, have been cloned and sequenced. Expression of modified sdhB
      together with sdhA in Escherichia coli led to overproduction of active His6
      tagged L-serine dehydratase. E. coli MEW22, deficient in the L-serine dehydratase
      L-SD1, was complemented by this sdhBA construct. The derived amino acid sequence
      of SdhBA shares similarities with both monomeric L-serine dehydratases, L-SD1 and
      L-SD2, from E. coli and with a putative L-serine dehydratase from Haemophilus
      influenzae, which suggests that these three enzymes are also iron-sulfur
      proteins.

PMID- 9244286
TI  - Structural and functional analysis of the phosphoenolpyruvate carboxylase gene
      from the purple nonsulfur bacterium Rhodopseudomonas palustris No. 7.
AB  - The ppc gene, encoding phosphoenolpyruvate carboxylase (PEPC), from
      Rhodopseudomonas palustris No. 7 was cloned and sequenced. Primer extension
      analysis identified a transcriptional start site 42 bp upstream of the ppc
      initiation codon. An R. palustris No. 7 PEPC-deficient strain showed a slower
      doubling time compared with the wild-type strain either anaerobically in the
      light or aerobically in the dark, when pyruvate was used as a carbon source.

PMID- 9244287
TI  - Identification and mutation of a gene required for glycerate kinase activity from
      a facultative methylotroph, Methylobacterium extorquens AM1.
AB  - A gene (gckA) responsible for the activity of glycerate kinase has been
      identified within a chromosomal fragment of the serine cycle methylotroph
      Methylobacterium extorquens AM1. A mutation in gckA leads to a specific C1
      negative phenotype. The polypeptide sequence derived from gckA showed high
      similarity to a product of ttuD essential for tartrate metabolism in
      Agrobacterium vitis. Our data suggest that gckA and ttuD might be structural
      genes for glycerate kinase and that the serine cycle and the tartrate utilization
      pathway share a series of reactions.

PMID- 9244288
TI  - Characterization of a periplasmic protein involved in iron utilization of
      Actinobacillus actinomycetemcomitans.
AB  - The periodontopathic bacterium Actinobacillus actinomycetemcomitans possesses a
      35-kDa periplasmic iron-repressible protein. Its regulation is mediated by the
      Fur protein, as was inferred from the Fur-binding consensus sequence at the -35
      position of the gene for the 35-kDa protein and from the relaxed expression of
      the gene in a mutant with an altered Fur-binding sequence. The 35-kDa protein,
      designated AfuA, has strong homology to HitA and FbpA of Haemophilus influenzae
      and Neisseria meningitidis, respectively, which serve as periplasmic iron
      transport proteins.

PMID- 9244289
TI  - Molecular and genetic characterization of the capsule biosynthesis locus of
      Streptococcus pneumoniae type 19B.
AB  - We have previously reported the nucleotide sequence of the Streptococcus
      pneumoniae type 19F capsular polysaccharide synthesis locus (cps19f), which
      consists of 15 open reading frames (ORFs) designated cps19fA to -O. Hybridization
      analysis indicated that close homologs for cps19fA to -H and cps19fK to -O were
      found in type 19B, but there were no homologs for cps19fI and -J. In this study
      we used long-range PCR to amplify and clone a 10.5-kb section of the S.
      pneumoniae type 19B capsule locus (cps19b) between cps19bH and cps19bK. This
      region of the cps19b locus is 4 kb larger than that in the cps19f locus and
      replaces cps19fI and cps19fJ with five new ORFs, designated cps19bP, -I, -Q, -R,
      and -J. We have proposed functions for four of the protein products, including
      functional homologs of Cps19fI and Cps19fJ. Transformation of a S. pneumoniae
      mutant containing an interrupted type 19F capsule locus with the 10.5-kb cps19b
      PCR product converted the recipient strain to type 19B. Southern hybridization
      analysis indicated that cps19bP, -I, -Q, -R, and -J are unique to type 19B and
      the closely related type 19C.

PMID- 9244290
TI  - A Bacillus subtilis gene encoding a protein similar to nucleotide sugar
      transferases influences cell shape and viability.
AB  - Bacillus subtilis gene ypfP, which is located at 196 degrees on the genetic map,
      shows similarity to both the monogalactosyldiacylglycerol synthase gene of
      Cucumis sativus, which encodes a galactosyltransferase, and the murG genes of B.
      subtilis, Escherichia coli, Haemophilus influenzae, and Synechocystis sp. strain
      PCC6803, which encode N-acetylglucosaminyltransferases involved in peptidoglycan
      biosynthesis. Cells containing a null mutation of ypfP are shorter and rounder
      than wild-type cells during growth in Luria-Bertani medium and glucose minimal
      medium. In addition, the mutant cells preferentially undergo lysis when grown on
      solid Luria-Bertani medium.

PMID- 9244292
TI  - Does COPI go both ways?

PMID- 9244291
TI  - Catching a Gli-mpse of Hedgehog.

PMID- 9244293
TI  - Protein folding in vivo: unraveling complex pathways.

PMID- 9244294
TI  - The recombination hot spot chi is embedded within islands of preferred DNA
      pairing sequences in the E. coli genome.

PMID- 9244295
TI  - Microtubule interaction site of the kinesin motor.
AB  - Kinesin and myosin are motor proteins that share a common structural core and
      bind to microtubules and actin filaments, respectively. While the actomyosin
      interface has been well studied, the location of the microtubule-binding site on
      kinesin has not been identified. Using alanine-scanning mutagenesis, we have
      found that microtubule-interacting kinesin residues are located in three loops
      that cluster in a patch on the motor surface. The critical residues are primarily
      positively charged, which is consistent with a primarily electrostatic
      interaction with the negatively charged tubulin molecule. The core of the
      microtubule-binding interface resides in a highly conserved loop and helix
      (L12/alpha5) that corresponds topologically to the major actin-binding domain of
      myosin. Thus, kinesin and myosin have developed distinct polymer-binding domains
      in a similar region with respect to their common catalytic cores.

PMID- 9244296
TI  - A model for the microtubule-Ncd motor protein complex obtained by cryo-electron
      microscopy and image analysis.
AB  - Kinesin motors convert chemical energy from ATP hydrolysis into unidirectional
      movement. To understand how kinesin motors bind to and move along microtubules,
      we fit the atomic structure of the motor domain of Ncd (a kinesin motor involved
      in meiosis and mitosis) into three-dimensional density maps of Ncd-microtubule
      complexes calculated by cryo-electron microscopy and image analysis. The model
      reveals that Ncd shares an extensive interaction surface with the microtubule,
      and that a portion of the binding site involves loops that contain conserved
      residues. In the Ncd dimer, the microtubule-bound motor domain makes intimate
      contact with its partner head, which is dissociated from the microtubule. This
      head-head interaction may be important in positioning the dissociated head to
      take a step to the next binding site on the microtubule protofilament.

PMID- 9244297
TI  - Hedgehog elicits signal transduction by means of a large complex containing the
      kinesin-related protein costal2.
AB  - The hedgehog gene of Drosophila melanogaster encodes a secreted protein (HH) that
      plays a vital role in cell fate and patterning. Here we describe a protein
      complex that mediates signal transduction from HH. The complex includes the
      products of at least three genes: fused (a protein-serine/threonine kinase),
      cubitus interruptus (a transcription factor), and costal2 (a kinesin-like
      protein). The complex binds with great affinity to microtubules in the absence of
      HH, but binding is reversed by HH. Mutations in the extracatalytic domain of FU
      abolish both the biological function of the protein and its association with
      COS2. We conclude that the complex may facilitate signaling from HH by governing
      access of the cubitus interruptus protein to the nucleus.

PMID- 9244298
TI  - Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway.
AB  - The Hedgehog (HH) signaling proteins control cell fates and patterning during
      animal development. In Drosophila, HH protein induces the transcription of target
      genes encoding secondary signals such as DPP and WG proteins by opposing a
      repressor system. The repressors include Costal2, protein kinase A, and the HH
      receptor Patched. Like HH, the kinase Fused and the transcription factor Cubitus
      interruptus (CI) act positively upon targets. Here we show that costal2 encodes a
      kinesin-related protein that accumulates preferentially in cells capable of
      responding to HH. COS2 is cytoplasmic and binds microtubules. We find that CI
      associates with COS2 in a large protein complex, suggesting that COS2 directly
      controls the activity of CI.

PMID- 9244299
TI  - Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for
      positioning the sites of tooth formation.
AB  - Vertebrate organogenesis is initiated at sites that are often morphologically
      indistinguishable from the surrounding region. Here we have identified Pax9 as a
      marker for prospective tooth mesenchyme prior to the first morphological
      manifestation of odontogenesis. We provide evidence that the sites of Pax9
      expression in the mandibular arch are positioned by the combined activity of two
      signals, one (FGF8) that induces Pax9 expression and the other (BMP2 and BMP4)
      that prevents this induction. Thus it appears that the position of the teeth is
      determined by a combination of two different types of signaling molecules
      produced in wide but overlapping domains rather than by a single localized
      inducer. We suggest that a similar mechanism may be used for specifying the sites
      of development of other organs.

PMID- 9244300
TI  - Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells
      by prechordal mesoderm.
AB  - Ventral midline cells at different rostrocaudal levels of the central nervous
      system exhibit distinct properties but share the ability to pattern the
      dorsoventral axis of the neural tube. We show here that ventral midline cells
      acquire distinct identities in response to the different signaling activities of
      underlying mesoderm. Signals from prechordal mesoderm control the differentiation
      of rostral diencephalic ventral midline cells, whereas notochord induces floor
      plate cells caudally. Sonic hedgehog (SHH) is expressed throughout axial mesoderm
      and is required for the induction of both rostral diencephalic ventral midline
      cells and floor plate. However, prechordal mesoderm also expresses BMP7 whose
      function is required coordinately with SHH to induce rostral diencephalic ventral
      midline cells. BMP7 acts directly on neural cells, modifying their response to
      SHH so that they differentiate into rostral diencephalic ventral midline cells
      rather than floor plate cells. Our results suggest a model whereby axial mesoderm
      both induces the differentiation of overlying neural cells and controls the
      rostrocaudal character of the ventral midline of the neural tube.

PMID- 9244301
TI  - Kuzbanian controls proteolytic processing of Notch and mediates lateral
      inhibition during Drosophila and vertebrate neurogenesis.
AB  - Notch and the disintegrin metalloprotease encoded by the kuzbanian (kuz) gene are
      both required for a lateral inhibition process during Drosophila neurogenesis. We
      show that a mutant KUZ protein lacking protease activity acts as a dominant
      negative form in Drosophila. Expression of such a dominant-negative KUZ protein
      can perturb lateral inhibition in Xenopus, leading to the overproduction of
      primary neurons. This suggests an evolutionarily conserved role for KUZ. The
      Notch family of receptors are known to be processed into smaller forms under
      normal physiological conditions. We provide genetic and biochemical evidence that
      Notch is an in vivo substrate for the KUZ protease, and that this cleavage may be
      part of the normal biosynthesis of functional Notch proteins.

PMID- 9244302
TI  - Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma
      membrane.
AB  - Previous models for signal transduction via the Notch pathway have depicted the
      full-length Notch receptor expressed at the cell surface. We present evidence
      demonstrating that the Notch receptor on the plasma membrane is cleaved. This
      cleavage is an evolutionarily conserved, general property of Notch and occurs in
      the trans-Golgi network as the receptor traffics toward the plasma membrane.
      Although full-length Notch is detectable in the cell, it does not reach the
      surface. Cleavage results in a C-terminal fragment, N(TM), that appears to be
      cleaved N-terminal to the transmembrane domain, and an N-terminal fragment,
      N(EC), that contains most of the extracellular region. We provide evidence that
      these fragments are tethered together on the plasma membrane by a link that is
      sensitive to reducing conditions, forming a heterodimeric receptor.

PMID- 9244303
TI  - Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling.
AB  - Two signaling molecules have been implicated in the modulation of immune receptor
      activation by inhibitory coreceptors: an inositol polyphosphate 5'-phosphatase,
      SHIP, and a tyrosine phosphatase, SHP-1. To address the necessity, interaction,
      or redundancy of these signaling molecules, we have generated SHP-1- or SHIP
      deficient B cell lines and determined their ability to mediate inhibitory
      signaling. Two distinct classes of inhibitory responses are defined, mediated by
      the selective recruitment of SHP-1 or SHIP. The Fc gammaRIIB class of inhibitory
      signaling is dependent on SHIP and not SHP-1; conversely, the KIR class requires
      SHP-1 and not SHIP. The consequence of this selective recruitment by inhibitory
      receptor engagement is seen in BCR-triggered apoptosis. SHP-1-mediated inhibitory
      signaling blocks apoptosis, while SHIP recruitment attenuates a proapoptotic
      signal initiated by Fc gammaRIIB.

PMID- 9244304
TI  - A human endogenous retroviral superantigen as candidate autoimmune gene in type I
      diabetes.
AB  - Microbial superantigens (SAGs) have been implicated in the pathogenesis of human
      autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor
      positive T cell subset in patients suffering from acute-onset type I diabetes has
      indicated the presence of a surface membrane-bound SAG. Here, we have isolated a
      novel mouse mammary tumor virus-related human endogenous retrovirus. We further
      show that the N-terminal moiety of the envelope gene encodes an MHC class II
      dependent SAG. We propose that expression of this SAG, induced in extrapancreatic
      and professional antigen-presenting cells, leads to beta-cell destruction via the
      systemic activation of autoreactive T cells. The SAG encoded by this novel
      retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.

PMID- 9244305
TI  - The regulation of anoikis: MEKK-1 activation requires cleavage by caspases.
AB  - Certain cell types undergo apoptosis when they lose integrin-mediated contacts
      with the extracellular matrix ("anoikis"). The Jun N-terminal kinase (JNK)
      pathway is activated in and promotes anoikis. This activation requires caspase
      activity. We presently report that a DEVD motif-specific caspase that cleaves
      MEKK-1 specifically is activated when cells lose matrix contact. This cleavage is
      required for the activation of the kinase activity. When overexpressed, the MEKK
      1 cleavage product stimulates apoptosis; the wild-type, full-length MEKK-1
      sensitizes cells to anoikis; and a cleavage-resistant mutant of MEKK-1 partially
      protects cells against anoikis. The cleavage-resistant or kinase-inactive mutants
      also prevent caspase-7 from being activated completely. Thus, caspases can induce
      apoptosis by activating MEKK-1, which in turn activates more caspase activity,
      comprising a positive feedback loop.

PMID- 9244306
TI  - The secretory granule protein syncollin binds to syntaxin in a Ca2(+)-sensitive
      manner.
AB  - The membrane proteins synaptobrevin, syntaxin, and SNAP-25 form the core of a
      ubiquitous fusion machine that interacts with the soluble proteins NSF and alpha
      SNAP. During regulated exocytosis, membrane fusion is usually strictly controlled
      by Ca2+ ions. However, the mechanism by which Ca2+ regulates exocytosis is still
      unclear. Here we show that the membranes of exocrine secretory granules contain
      an 18-kDa protein, syncollin, that binds to syntaxin at low Ca2+ concentrations
      and dissociates at concentrations known to stimulate exocytosis. Syncollin has a
      single hydrophobic domain at its N-terminus and shows no significant homology
      with any known protein. Recombinant syncollin inhibits fusion in vitro between
      zymogen granules and pancreatic plasma membranes, and its potency falls as Ca2+
      concentration rises. We suggest that syncollin acts as a Ca2(+)-sensitive
      regulator of exocytosis in exocrine tissues.

PMID- 9244307
TI  - Bidirectional transport by distinct populations of COPI-coated vesicles.
AB  - Electron microscope immunocytochemistry reveals that both anterograde-directed
      (proinsulin and VSV G protein) and retrograde-directed (the KDEL receptor) cargo
      are present in COPI-coated vesicles budding from every level of the Golgi stack
      in whole cells; however, they comprise two distinct populations that together can
      account for at least 80% of the vesicles budding from Golgi cisternae.
      Segregation of anterograde- from retrograde-directed cargo into distinct sets of
      COPI-coated vesicles is faithfully reproduced in the cell-free Golgi transport
      system, in which VSV G protein and KDEL receptor are packaged into separable
      vesicles, even when budding is driven by highly purified coatomer and a
      recombinant ARF protein.

PMID- 9244308
TI  - The C-terminal domain of TolA is the coreceptor for filamentous phage infection
      of E. coli.
AB  - Filamentous bacteriophages infecting gram-negative bacteria display tropism for a
      variety of pilus structures. However, the obligatory coreceptor of phage
      infection, postulated from genetic studies, has remained elusive. Here we
      identify the C-terminal domain of the periplasmic protein TolA as the coreceptor
      for infection of Escherichia coli by phage fd and the N-terminal domain of the
      phage minor coat protein g3p as its cognate ligand. The neighboring g3p domain
      binds the primary receptor of phage infection, the F pilus, and blocks TolA
      binding in its absence. Contact with the pilus releases this blockage during
      infection. Our findings support a sequential two-way docking mechanism for phage
      infection, analogous to infection pathways proposed for a range of eukaryotic
      viruses including herpes simplex, adenoviruses, and also lentiviruses like HIV-1.

PMID- 9244309
TI  - Structural adaptations in the specialized bacteriophage T4 co-chaperonin Gp31
      expand the size of the Anfinsen cage.
AB  - The Gp31 protein from bacteriophage T4 functionally substitutes for the bacterial
      co-chaperonin GroES in assisted protein folding reactions both in vitro and in
      vivo. But Gp31 is required for the folding and/or assembly of the T4 major capsid
      protein Gp23, and this requirement cannot be satisfied by GroES. The 2.3 A
      crystal structure of Gp31 shows that its tertiary and quaternary structures are
      similar to those of GroES despite the existence of only 14% sequence identity
      between the two proteins. However, Gp31 shows a series of structural adaptations
      which will increase the size and the hydrophilicity of the "Anfinsen cage," the
      enclosed cavity within the GroEL/GroES complex that is the location of the
      chaperonin-assisted protein folding reaction.

PMID- 9244310
TI  - Identification and characterization of an IkappaB kinase.
AB  - Activation of the transcription factor NF-kappaB by tumor necrosis factor (TNF)
      and interleukin-1 (IL-1) requires the NF-kappaB-inducing kinase (NIK). In a yeast
      two-hybrid screen for NIK-interacting proteins, we have identified a protein
      kinase previously known as CHUK. Overexpression of CHUK activates a NF-kappaB
      dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant
      negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-kappaB activation.
      CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in
      mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both serine 32
      and serine 36, modifications that are required for targeted degradation of
      IkappaB-alpha via the ubiquitin-proteasome pathway. This phosphorylation of
      IkappaB-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK
      activated IkappaB-alpha kinase that links TNF- and IL-1-induced kinase cascades
      to NF-kappaB activation.

PMID- 9244311
TI  - Biological weapons control. Prospects and implications for the future.
AB  - The Biological and Toxin Weapons Convention (BWC), which prohibits the
      acquisition of biological materials for hostile purposes and armed conflict,
      entered into force in 1975 and now has the participation of 140 nations (158
      nations have signed the BWC, but only 140 of these have also ratified it).
      However, there is no monitoring mechanism associated with the BWC. Diplomatic
      efforts are now under way to create a supplemental, legally binding protocol to
      strengthen the convention. Measures to strengthen the BWC are analogous to the
      diagnostic processes familiar to physicians; the problem facing negotiators is to
      identify procedures with high positive and negative predictive value. Few
      proposed measures meet these criteria. However, the investigation of unusual
      disease outbreaks and allegations of use are highly diagnostic of illicit
      activities while avoiding false-positive accusations. At the same time, such
      information generated by the BWC can contribute to worldwide efforts to improve
      public health, control emergent disease, and establish an international norm
      against biological weapons proliferation.

PMID- 9244312
TI  - Biological weapons and US law.
AB  - During the past 8 years, the US Congress has developed a comprehensive legal
      framework to prevent the illegitimate use of toxins and infectious agents. As
      part of this framework, Congress has defined as a federal crime virtually every
      step in the process of developing or acquiring a biological agent for use as a
      weapon. At the same time, Congress has vested federal law enforcement agencies
      with broad civil and investigative powers to enable the government to intervene
      before such weapons are used or even developed. Finally, Congress has directed
      the Centers for Disease Control and Prevention to establish a regulatory regime
      to monitor the location and transfer of hazardous biological agents and to insure
      that any use of such agents complies with appropriate biosafety requirements.

PMID- 9244313
TI  - National health and medical services response to incidents of chemical and
      biological terrorism.
AB  - In response to the growing threat of terrorism with chemical and biological
      weapons, the US government has developed a national concept of operations for
      emergency health and medical services response. This capability was developed and
      tested for the first time during the Atlanta Olympic Games in the summer of 1996.
      In the event of a chemical or biological terrorist incident that exceeded local
      and state-level response capabilities, federal agencies would provide specialized
      teams and equipment to help manage the consequences of the attack and treat,
      decontaminate, and evacuate casualties. The US Congress has also established a
      Domestic Preparedness Program that provides for enhanced training of local first
      responders and the formation of metropolitan medical strike teams in major cities
      around the country. While these national response capabilities are promising,
      their implementation to date has been problematic and their ultimate
      effectiveness is uncertain.

PMID- 9244314
TI  - The complementary role of environmental and security biological control regimes
      in the 21st century.
AB  - As we approach the 21st century, there is increased worldwide concern about
      disease, whether natural or deliberate, in humans, animals, and plants. There are
      2 driving forces for multilateral biological control regimes:
      international/national security and environmental protection. With respect to
      deliberately caused disease, these seemingly disparate forces are mutually
      reinforcing as demonstrated by simultaneous moves to strengthen the Biological
      and Toxin Weapons Convention and the entry into force of the Convention on
      Biological Diversity. Future multilateral biological control regimes based on
      these developments will aid the security, prosperity, and health of the world
      community.

PMID- 9244315
TI  - Pentagon-funded research takes aim at agents of biological warfare.

PMID- 9244316
TI  - Physician group declares war on land mine injuries.

PMID- 9244317
TI  - Health care leaders form drug policy group.

PMID- 9244318
TI  - From the Food and Drug Administration.

PMID- 9244319
TI  - From the Centers for Disease Control and Prevention. Fatal human plague--Arizona
      and Colorado, 1996.

PMID- 9244320
TI  - From the Centers for Disease Control and Prevention. Community report cards-
      United States, 1996.

PMID- 9244321
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244322
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244323
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244324
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244325
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244326
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244327
TI  - Identification of Gulf War syndrome: methodological issues and medical illnesses.

PMID- 9244328
TI  - Production and use of biological weapons: need for international sanctions?

PMID- 9244329
TI  - Efficacy of midodrine for neurogenic orthostatic hypotension.

PMID- 9244330
TI  - A large community outbreak of salmonellosis caused by intentional contamination
      of restaurant salad bars.
AB  - CONTEXT: This large outbreak of foodborne disease highlights the challenge of
      investigating outbreaks caused by intentional contamination and demonstrates the
      vulnerability of self-service foods to intentional contamination. OBJECTIVE: To
      investigate a large community outbreak of Salmonella Typhimurium infections.
      DESIGN: Epidemiologic investigation of patients with Salmonella gastroenteritis
      and possible exposures in The Dalles, Oregon. Cohort and case-control
      investigations were conducted among groups of restaurant patrons and employees to
      identify exposures associated with illness. SETTING: A community in Oregon.
      Outbreak period was September and October 1984. PATIENTS: A total of 751 persons
      with Salmonella gastroenteritis associated with eating or working at area
      restaurants. Most patients were identified through passive surveillance; active
      surveillance was conducted for selected groups. A case was defined either by
      clinical criteria or by a stool culture yielding S Typhimurium. RESULTS: The
      outbreak occurred in 2 waves, September 9 through 18 and September 19 through
      October 10. Most cases were associated with 10 restaurants, and epidemiologic
      studies of customers at 4 restaurants and of employees at all 10 restaurants
      implicated eating from salad bars as the major risk factor for infection. Eight
      (80%) of 10 affected restaurants compared with only 3 (11%) of the 28 other
      restaurants in The Dalles operated salad bars (relative risk, 7.5; 95% confidence
      interval, 2.4-22.7; P<.001). The implicated food items on the salad bars differed
      from one restaurant to another. The investigation did not identify any water
      supply, food item, supplier, or distributor common to all affected restaurants,
      nor were employees exposed to any single common source. In some instances,
      infected employees may have contributed to the spread of illness by inadvertently
      contaminating foods. However, no evidence was found linking ill employees to
      initiation of the outbreak. Errors in food rotation and inadequate refrigeration
      on ice-chilled salad bars may have facilitated growth of the S Typhimurium but
      could not have caused the outbreak. A subsequent criminal investigation revealed
      that members of a religious commune had deliberately contaminated the salad bars.
      An S Typhimurium strain found in a laboratory at the commune was
      indistinguishable from the outbreak strain. CONCLUSIONS: This outbreak of
      salmonellosis was caused by intentional contamination of restaurant salad bars by
      members of a religious commune.

PMID- 9244331
TI  - An outbreak of Shigella dysenteriae type 2 among laboratory workers due to
      intentional food contamination.
AB  - CONTEXT: Shigella dysenteriae type 2 is rare in the United States, and outbreaks
      associated with this pathogen are uncommon. OBJECTIVE: To determine the magnitude
      and source of an outbreak of S dysenteriae type 2. DESIGN: Retrospective cohort.
      SETTING: Laboratory of a large medical center. PATIENTS: Case patients were
      identified as laboratory workers who had diarrhea on or after October 28 and a
      positive stool culture or temperature greater than 37.8 degrees C. Laboratory
      workers with diarrhea only were probable case patients. MAIN OUTCOME MEASURES: We
      interviewed laboratory staff and performed identification, serotyping, and pulsed
      field gel electrophoresis on isolates from case patients, implicated food, and
      laboratory stock culture. RESULTS: From October 29 through November 1, a total of
      12 (27%) of 45 laboratory staff developed severe, acute diarrheal illness; 8 had
      S dysenteriae isolated from stool and 4 were hospitalized. All case patients
      reported having eaten muffins or doughnuts placed in the staff break room on
      October 29. Pulsed-field gel electrophoresis showed stool isolates from 9 case
      patients were indistinguishable from S dysenteriae type 2 recovered from an
      uneaten muffin and from the laboratory's stock strain, a portion of which was
      missing. CONCLUSIONS: The source of the outbreak was most likely the laboratory's
      stock culture, which was used to contaminate the pastries. Results of this
      investigation underscore the need for adequate precautions to prevent inadvertent
      or intentional contamination from highly pathogenic laboratory specimens.

PMID- 9244332
TI  - Clinical recognition and management of patients exposed to biological warfare
      agents.
AB  - Concern regarding the use of biological agents--bacteria, viruses, or toxins--as
      tools of warfare or terrorism has led to measures to deter their use or, failing
      that, to deal with the consequences. Unlike chemical agents, which typically lead
      to violent disease syndromes within minutes at the site of exposure, diseases
      resulting from biological agents have incubation periods of days. Therefore,
      rather than a paramedic, it will likely be a physician who is first faced with
      evidence of the results of a biological attack. We provide here a primer on 10
      classic biological warfare agents to increase the likelihood of their being
      considered in a differential diagnosis. Although the resultant diseases are
      rarely seen in many countries today, accepted diagnostic and epidemiologic
      principles apply; if the cause is identified quickly, appropriate therapy can be
      initiated and the impact of a terrorist attack greatly reduced.

PMID- 9244333
TI  - Biological warfare. A historical perspective.
AB  - The deliberate use of microorganisms and toxins as weapons has been attempted
      throughout history. Biological warfare has evolved from the crude use of cadavers
      to contaminate water supplies to the development of specialized munitions for
      battlefield and covert use. The modern development of biological agents as
      weapons has paralleled advances in basic and applied microbiology. These include
      the identification of virulent pathogens suitable for aerosol delivery and
      industrial-scale fermentation processes to produce large quantities of pathogens
      and toxins. The history of biological warfare is difficult to assess because of a
      number of confounding factors. These include difficulties in verification of
      alleged or attempted biological attacks, the use of allegations of biological
      attacks for propaganda purposes, the paucity of pertinent microbiological or
      epidemiologic data, and the incidence of naturally occurring endemic or epidemic
      diseases during hostilities. Biological warfare has been renounced by 140
      nations, primarily for strategic and other pragmatic reasons. International
      diplomatic efforts, including the 1972 Biological Weapons Convention, have not
      been entirely effective in preventing the enhancement and proliferation of
      offensive biological warfare programs. The threats posed by biological weapons
      are likely to continue into the future.

PMID- 9244334
TI  - Iraq's biological weapons. The past as future?
AB  - Between 1985 and April 1991, Iraq developed anthrax, botulinum toxin, and
      aflatoxin for biological warfare; 200 bombs and 25 ballistic missiles laden with
      biological agents were deployed by the time Operation Desert Storm occurred.
      Although cause for concern, if used during the Persian Gulf War, Iraq's
      biological warfare arsenal probably would have been militarily ineffective for 3
      reasons: (1) it was small; (2) payload dispersal mechanisms were inefficient; and
      (3) coalition forces dominated the theater of war (ie, they had overwhelming air
      superiority and had crippled Iraq's command and control capability). Despite the
      Gulf War defeat, the Iraqi biological warfare threat has not been extinguished.
      Saddam Hussein remains in power, and his desire to acquire weapons of mass
      destruction continues unabated. In this context, the international community must
      be firm in its enforcement of United Nations resolutions designed to deter Iraq
      from reacquiring biological warfare capability and must take steps to develop a
      multidisciplinary approach to limiting future development of weapons of mass
      destruction.

PMID- 9244335
TI  - The threat of biological weapons. Prophylaxis and mitigation of psychological and
      social consequences.
AB  - The microbial world is mysterious, threatening, and frightening to most people.
      The stressors associated with a biological terrorist attack could create high
      numbers of acute and potentially chronic psychiatric casualties who must be
      recognized, diagnosed, and treated to facilitate triage and medical care. Media
      communications, planning for quarantine and decontamination, and the role of
      community leaders are important to the mitigation of psychological consequences.
      Physicians will need to accurately diagnose anxiety, depression, bereavement, and
      organic brain syndromes to provide treatment, reassurance, and the relief of
      pain.

PMID- 9244336
TI  - Biological terrorism. Preparing to meet the threat.
AB  - The threat of terrorists using biological warfare agents has received increased
      attention in recent years. Despite the hope that, with the right mix of policies,
      security measures, and intelligence gathering, a major biological warfare
      terrorist attack can be prevented, the history of conventional terrorism
      indicates otherwise. The greatest payoff in combating biological terrorism lies
      in focusing on how best to respond to a terrorist attack. The medical and
      emergency service communities will play the most important role in that process.
      Ensuring that they are trained to recognize the symptoms of diseases caused by
      biological warfare agents and have Critical Incident Stress Debriefing teams
      available to help them cope with the emotional aspects of treating exposed
      survivors should be part of contingency planning. By improving our readiness to
      respond to biological terrorism, many lives can be saved and terrorists denied
      their goal of creating panic and crisis throughout the country.

PMID- 9244337
TI  - Why should we be concerned about biological warfare?

PMID- 9244338
TI  - Botulism surveillance and emergency response. A public health strategy for a
      global challenge.

PMID- 9244339
TI  - Infectious disease and biological weapons. Prophylaxis and mitigation.

PMID- 9244340
TI  - The agents of biological warfare.

PMID- 9244341
TI  - Gene activating and proapoptotic potential are independent properties of
      different CD4 epitopes.
AB  - CD4 engagement triggers an early signaling cascade which initiates late events
      such as transcription factor activation. The outcome of CD4 engagement is T-cell
      commitment to alternative, dramatically different fates, such as activation and
      apoptosis. We have tested a panel of anti-CD4 mAbs specific for different CD4
      epitopes, as well as HIV-1 gp120, for the capacity to activate crucial early
      events such as enhancement of p56(lck) kinase activity and Shc phosphorylation.
      The same CD4 epitopes were characterized for their capacity both to deliver a
      gene activating signal and to program T-cells to activation dependent death. No
      correlation could be found between capacity of specific CD4 epitopes to deliver a
      gene activating signal and capacity to prime T-cells to apoptosis, suggesting
      that gene activating and proapoptotic potential are independent functions of CD4
      epitopes. Furthermore, while triggering of the calcium pathway appears critical
      in NF-AT activation, optimal p56(lck) activation and Shc phosphorylation might be
      required for initiation of the apoptotic pathway.

PMID- 9244342
TI  - Primary sequence of baboon CR1 demonstrates concerted evolution within the CR1
      gene.
AB  - Complement receptor type one (CR1) in primates has several remarkable structural
      features including a size polymorphism (Mr 190000, 220000, 250000 and 280000) in
      man, multiple size variants (Mr 55000-220000) among non-human primates, and a
      partial amino-terminal duplication (CR1-like gene) that appears to encode the
      short (55000-70000) forms expressed on primate erythrocytes. In general, these
      short CR1 forms, some of which are GPI anchored, are expressed on erythrocytes
      and the 220000 molecular weight CR1 form is expressed on PBMC, except in man,
      where only the 220000 molecular weight form has been detected. In addition, the
      Mr 220000 human CR1 sequence carries several long internal repeats of up to 99%
      homology. It has been suggested that the highest homology is maintained by gene
      conversion and/or unequal crossover. To address further the evolutionary and
      biologic implications of these multiple forms, a 6 kb cDNA encoding baboon
      CR1(220) was identified by RTPCR using human CR1 primers. Its sequence contains
      the expected 30 complement control protein repeats (CCP) and demonstrates an
      overall homology to human CR1 of 95.4% at the nucleotide level and 93.2% at the
      amino acid level. As in human CR1, the first 28 CCP maintain the characteristic
      "seven CCP-long homologous repeats (LHR)" organization. Analysis of baboon
      CR1(220) indicates that horizontal or concerted evolution has maintained a high
      degree (> 98%) of identity between corresponding CCP within the LHRs from CCP 4
      to CCP 19, while this homology region extends from CCP 3 to CCP 18 in man. In
      contrast, substitutions occurring in other CCP are not propagated to the
      corresponding sites of other LHR. Sequence differences in CCP 1, 2 and 3 are
      likely to be related to the acquisition of enhanced C3b binding capability by
      this amino-terminal region of the protein. Thus, the sequence data strongly
      support the hypotheses that gene conversion and or unequal crossover events have
      driven the evolution of the protein in regions of high homology while selective
      forces, probably ligand binding requirements, have maintained the regions of
      divergence.

PMID- 9244343
TI  - Immunoglobulin VH gene replacements in a T-cell lymphoblastic lymphoma.
AB  - We have analysed the rearrangement status of the immunoglobulin heavy (IgH) chain
      locus during progression of a T-cell lymphoblastic lymphoma displaying multiple
      IgH rearrangements as demonstrated by variable heavy (VH) gene family specific
      polymerase chain reaction (PCR) analysis. The tumor was found to undergo
      diversification at the IgH locus between diagnosis and relapse through a
      mechanism of VH to VHDJH replacement. In subsets of the tumor at relapse, two
      separate VH gene segments were found to have replaced the VH gene utilized by a
      VHDJH rearrangement identified at diagnosis. The observed VH gene replacement
      events appear to have been mediated by a heptamer sequence homologous to the
      heptamer of the recombination signal sequence (RSS) located internally in the VH
      gene segment. These results support the notion that VH replacements contribute to
      the diversification of immunoglobulin genes.

PMID- 9244344
TI  - Mutagenesis of an immunodominant T cell epitope can affect recognition of
      different T and B determinants within the same antigen.
AB  - The effects of mutagenesis of residues of a major T cell epitope were
      investigated in order to expand knowledge from synthetic peptides to the
      naturally processed antigen. The impact of substitutions within the core of the
      immunodominant p61-80/PT19 mycobacterial epitope was ascertained in respect of
      this epitope per se, or of a C-terminal (140-159) overlapping T/B epitope and of
      a conformational B epitope. The core substitution A71L impaired T immunogenicity
      of the target epitope within the protein, but not in the peptide, whereas the
      N73A substitution impaired the responses in both instances. Notably, each of
      these single amino acid mutations abrogated the T but not the B immunogenicity of
      the C-terminal epitope. Furthermore, mutation of five core residues (71-76) also
      ablated expression of a monoclonal antibody defined conformational B epitope. In
      conclusion, immunological analysis of mutated proteins revealed functional
      associations between topographically distinct antigenic determinants which may
      account for the previously observed differences in the specificity of immune
      responses between immunised and infected hosts.

PMID- 9244345
TI  - Late events in assembly determine the polymeric structure and biological activity
      of secretory IgM.
AB  - IgM antibodies can be secreted in at least two functional polymeric forms that
      can be distinguished according to subunit composition. While IgM hexamers
      comprise six H2L2 monomeric subunits, pentamers contain an additional
      polypeptide, the J chain. In the presence of high abundance J chain protein, IgM
      pentamers are preferentially assembled at the expense of hexamers. To determine
      the mechanism by which J chain regulates the assembly process, we defined the
      point at which J chain is added to assembling polymers. We found no evidence for
      the presence of J chain in small IgM assembly intermediates of IgM, suggesting
      that it was not stably associated with these complexes. However, J chain was
      found associated with large polymeric IgM complexes exhibiting sedimentation
      properties of intracellular pentameric structures. These complexes were
      frequently not completely covalently assembled; however, complete covalent
      assembly of J chain-containing pentameric complexes did occur prior to their
      maturation in the Golgi. These data argue that pentameric structures are the
      substrate for J chain incorporation into assembling IgM and suggest that the
      incorporation of J chain is thermodynamically favored over the addition of a
      sixth monomeric subunit into an assembling polymer. We conclude that late events
      in IgM polymer assembly, specifically the insertion of J chain, the exclusion of
      an additional monomeric subunit, and the covalent closure of the pentameric IgM
      molecule, determine the polymeric structure and, consequently, the biological
      activity of secreted IgM.

PMID- 9244346
TI  - Transcription of germline VH gene elements by normal human fetal liver.
AB  - Transcription of the gene elements that form the variable region of
      immunoglobulin heavy chains has been proposed to represent the process that
      controls access for the recombination enzymes in their sequential steps of
      catalysis. Evidence for germline transcription of VH gene elements, as part of VH
      to DJH recombination, has been limited to transcripts of only a few gene
      elements. We have examined normal fetal liver mRNA by Northern blotting and
      present evidence for germline transcripts from six human VH gene families. The
      candidate VH4 transcripts have been confirmed as germline transcripts by
      hybridization with 3' flanking sequences that would have been removed by
      recombination from mature VHDJH genes. The candidate transcripts for VH1, VH3,
      VH4 and VH6 have been confirmed by polymerase chain reaction amplification with
      primers from the 3' flanking sequences of these gene families and determination
      of the sequence of these products. Determination of sequence from two clones of
      VH1, VH3 and VH4 indicates that more than one gene from each of these families is
      transcribed. PCR amplification of VH4 and VH6 with primers specific for the
      leader sequence (exon 1) and 3' flanking sequence indicate that these transcripts
      are spliced, representing RNA processing. Germline transcripts from these
      families are also present in normal human bone marrow. These results indicate
      that transcriptional activation of germline VH gene elements is a general
      phenomenon in tissues undergoing V to DJ recombination.

PMID- 9244347
TI  - I-A beta gene expression regulation in macrophages derived from mice susceptible
      or resistant to infection with M. bovis BCG.
AB  - The innate capacity of mice to control mycobacterial multiplication early after
      infection is controlled by the resistant allele of the Nramp-1/Bcg gene. The Bcg
      gene seems to be involved in a pathway leading to macrophage activation. It
      differentially affects the ability of BCG-resistant and -susceptible strains of
      mice to express important macrophage genes including Major Histocompatibility
      Complex (MHC) class II genes. An inhibition of Nramp1 gene by Nramp1-ribozyme
      transfection in macrophages resulted in the impairment of MHC class II gene
      induction by IFN gamma. In this study, we have investigated the molecular
      mechanisms involved in IFN-gamma-induced MHC class II expression using
      macrophages derived from mice resistant or susceptible to mycobacterial
      infections (B10R and B10S, respectively). We have found that the difference in
      the IFN gamma-induced Ia surface protein expression between B10R and B10S
      macrophages correlate with a higher rate of I-A beta gene transcription. We have
      also studied the binding of proteins prepared from nuclear extracts of non
      stimulated and IFN-gamma-stimulated B10R and B10S macrophages to the S, X and Y
      cis-acting elements of the I-A beta promoter. Differences observed in protein
      binding to the X box may explain the difference in transcription activation of
      the I-A beta gene. We have also found that I-A alpha and I-A beta mRNA half-lives
      measured in IFN gamma-stimulated cells are significantly longer in B10R, compared
      to B10S macrophages. Overall, our data suggest that both transcriptional and
      posttranscriptional regulatory mechanisms are responsible for the more efficient
      expression of I-A beta gene in macrophages carrying a resistant allele of Nramp1
      gene.

PMID- 9244348
TI  - Base transitions dominate the mutational spectrum of a transgenic reporter gene
      in MSH2 deficient mice.
AB  - Tumors derived from individuals with hereditary nonpolyposis colorectal cancer
      syndrome frequently demonstrate mutations in both alleles of hMSH2, a key gene in
      DNA mismatch repair (MMR). Sporadic tumors also frequently exhibit MMR
      deficiency. In keeping with the role of MMR in the maintenance of genome
      integrity, mice deficient in MSH2 via gene targeting demonstrate a high incidence
      of thymic lymphomas and small intestinal adenocarcinomas. To investigate the
      effects of MSH2 deficiency in normal tissues, mice containing a retrievable
      transgenic lacI reporter gene for mutation detection were crossed with MSH2-/-
      mice. Mice homozygous for MSH2 deficiency revealed 4.8, 11.0 and 15.2-fold
      elevations in spontaneous mutation frequency in DNA obtained from brain, small
      intestine, and thymus, respectively, as compared to heterozygous or wild-type
      mice. Mutations most frequently recovered from MSH2-/- mice were single base
      substitutions (77%), particularly base transitions (64%). Frameshifts occurred
      less frequently (19%) and fell within very short (3-5 bp) mononucleotide runs.
      Thus the number of key growth control genes potentially impacted by MMR
      deficiency extends beyond those containing repetitive sequences. These results
      highlight the capacity for MSH2 deficiency to serve as a potent driving force
      during the multi-step evolution of tumors.

PMID- 9244349
TI  - gamma-Ray-induced apoptosis in transgenic mice with proliferative abnormalities
      in their intestinal epithelium: re-entry of villus enterocytes into the cell
      cycle does not affect their radioresistance but enhances the radiosensitivity of
      the crypt by inducing p53.
AB  - The radiosensitivity of proliferating crypt epithelial cells makes the gut a
      major limiting factor in the use of radiotherapy for treatment of abdominal
      cancers. As post-mitotic epithelial cells migrate from mouse small intestinal
      crypts to the base of adjacent villi, they rapidly lose their ability to undergo
      apoptosis in response to ionizing irradiation (IR). To determine whether this
      radioresistance reflects withdrawal from the cell cycle, we used a lineage
      specific promoter to direct expression of wild type Simian virus 40 T antigen
      (SV40 TAg(Wt)) to villus, but not crypt, enterocytes in FVB/N transgenic mice.
      SV40 TAg(Wt) induced, pRB-dependent, re-entry into the cell cycle is not
      associated with the acquisition of IR-stimulated apoptosis 4 h or 24 h after 6 Gy
      or 12 Gy of gamma-irradiation. Co-expression of SV40 TAg(Wt) and K-ras(val12)
      produces dysplasia in cycling villus enterocytes but no shift towards apoptotic
      responsiveness to IR. These findings suggest that the radioresistance of villus
      enterocytes is not simply due to their cell cycle arrest and may be a reflection
      of their microenvironment. Remarkably, reentry of villus enterocytes to the cell
      cycle increases the radiosensitivity of the crypt epithelium without changing Bcl
      2, Bcl-xL, Bak, or Bax expression. This effect is only manifest after IR and,
      based upon results obtained with mutant SV40 TAgs, depends upon reaching a
      critical level of proliferation in villus enterocytes. Like the normal crypt
      response to IR, the villus-derived enhancement of IR-stimulated crypt apoptosis
      is associated with an induction of p53 and Raf-1, and is dependent upon p53.
      Unlike the normal crypt response to IR, the p53 induction involves cells
      distributed throughout the crypt and the apoptotic response is not confined to
      the lower half of the crypt. These results indicate that signals initiated by
      cycling enterocytes can be transmitted to the crypt epithelium to induce p53 and
      influence their IR-induced apoptosis. Understanding the underlying signaling
      pathways may provide clues about how to modify a normal crypt's radiosensitivity
      for therapeutic benefit.

PMID- 9244350
TI  - BRCA1 proteins are transported to the nucleus in the absence of serum and splice
      variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F,
      cyclins and cyclin dependent kinases.
AB  - BRCA1, a familial breast and ovarian cancer susceptibility gene encodes nuclear
      phosphoproteins that function as tumor suppressors in human breast cancer cells.
      Previously, we have shown that overexpression of a BRCA1 splice variant BRCA1a
      accelerates apoptosis in human breast cancer cells. In an attempt to determine
      whether the subcellular localization of BRCA1 is cell cycle regulated, we have
      studied the subcellular distribution of BRCA1 in asynchronous and growth arrested
      normal, breast and ovarian cancer cells using different BRCA1 antibodies by
      immunofluorescence and immunohistochemical staining. Upon serum starvation of
      NIH3T3, some breast and ovarian cancer cells, most of the BRCA1 protein
      redistributed to the nucleus revealing a new type of regulation that may modulate
      the activity of BRCA1 gene. We have also characterized two new variant BRCA1
      proteins (BRCA1a/p110 and BRCA1b/ p100) which are phosphoproteins containing
      phosphotyrosine. Immunofluorescence and Western blotting analysis indicate
      cytoplasmic and nuclear localization of BRCA1a and BRCA1b proteins. To elucidate
      the biological function of BRCA1, we created a bacterial fusion protein of
      glutathione-transferase (GST) and BRCA1 zinc finger domain and detected two
      cellular proteins with molecular weights of approximately 32 and 65 kD, one of
      which contains phosphotyrosine designated p32 and p65 BRCA1 interacting proteins
      (BIP) that specifically interact with BRCA1. Western blot analysis of BIP with
      cyclins/CDKs and E2F antisera indicated association with cdc2, cdk2, cdk4, cyclin
      B, cyclin D, cyclin A and E2F-4 but not with cdk3, cdk5, cdk6, E2F-1, E2F-2, E2F
      3, E2F-5 and cyclin E. Furthermore, we have also demonstrated a direct
      interaction of in vitro translated BRCA1a and BRCA1b proteins with recombinant
      cyclin A, cyclin B1, cyclin D1, cdc2, cdk2 and E2F fusion proteins in vitro.
      Taken together these results seem to suggest that BRCA1 could be an important
      negative regulator of cell cycle that functions through interaction with E2F
      transcriptional factors and phosphorylation by cyclins/cdk complexes with the
      zinc ring finger functioning as a major protein-protein interaction domain. If
      the interactions we observe in vitro is also seen in vivo then it may be possible
      that lack or impaired binding of the disrupted BRCA1 proteins to E2F,
      cyclins/CDKs in patients with mutations in the zinc finger domain could deprive
      the cell of an important mechanism for braking cell proliferation leading to the
      development of breast and ovarian cancers.

PMID- 9244351
TI  - Recombinant ATM protein complements the cellular A-T phenotype.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by
      neurodegeneration, immunodeficiency, cancer predisposition, genome instability
      and radiation sensitivity. The cellular phenotype of A-T points to defects in
      signal transduction pathways involved in activation of cell cycle checkpoints by
      free radical damage, and other pathways that mediate the transmission of specific
      mitogenic stimuli. The product of the responsible gene, ATM, belongs to a family
      of large proteins that contribute to maintaining genome stability and cell cycle
      progression in various organisms. A recombinant vector that stably expresses a
      full-length ATM protein is a valuable tool for its functional analysis. We
      constructed and cloned a recombinant, full-length open reading frame of ATM using
      a combination of vectors and hosts that overcame an inherent instability of this
      sequence. Recombinant ATM was stably expressed in insect cells using a
      baculovirus vector, albeit at a low level, and in human A-T cells using an
      episomal expression vector. An amino-terminal FLAG epitope added to the protein
      allowed highly specific detection of the recombinant molecule by immunoblotting,
      immunoprecipitation and immunostaining, and its isolation using immunoaffinity.
      Similar to endogenous ATM, the recombinant protein is located mainly in the
      nucleus, with low levels in the cytoplasm. Ectopic expression of ATM in A-T cells
      restored normal sensitivity to ionizing radiation and the radiomimetic drug
      neocarzinostatin, and a normal pattern of post-irradiation DNA synthesis, which
      represents an S-phase checkpoint. These observations indicate that the
      recombinant, epitope-tagged protein is functional. Introduction into this
      molecule of a known A-T missense mutation, Glu2904Gly, resulted in apparent
      instability of the protein and inability to complement the A-T phenotype. These
      findings indicate that the physiological defects characteristic of A-T cells
      result from the absence of the ATM protein, and that this deficiency can be
      corrected by ectopic expression of this protein.

PMID- 9244352
TI  - The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell
      lines. Is H19 a tumor suppressor gene?
AB  - H19 is a paternally imprinted gene with unknown function. It is located in close
      proximity to the maternally imprinted IGF-2 gene on chromosome 11p15.5. In this
      study no consistent relationship between the expression of these two genes in
      clones derived from JEG-3 and JAr cell lines could be detected. Nor could a
      consistent relationship be detected between the expression levels of these two
      genes and between certain characteristic tumorigenic properties of these clones.
      We included in this study clones, expressing low H19 levels, which after
      transfection with an H19 expression construct highly expressed the H19 gene. In
      tumors, formed by the injection of cells of JAr or JEG-3 clones into nude mice,
      the H19 expression was high and irrelevant to the expression level in the cells
      before the injection. The same phenomenon was found for IGF-2 expression during
      tumorigenesis caused by cells of different JEG-3 clones and in some but not all
      JAr derived clones. Both H19 and IGF-2 are biallelicly expressed in all the JAr
      and JEG-3 clones. In summary, our observations point to the conclusion that H19
      is not a tumor suppressor gene. However, its high expression in all the tumors
      formed after injection of cells of the JAr and JEG-3 clones, leaves its role, if
      any, in choriocarcinogenesis an open question.

PMID- 9244353
TI  - Mutual requirement of CDK4 and Myc in malignant transformation: evidence for
      cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc.
AB  - We demonstrate in this paper that CDK4 which is a G1 phase specific cell cycle
      regulator and catalytic subunit of D-type cyclins has oncogenic activity similar
      to D-type cyclins themselves and is able to provoke focus formation when
      cotransfected with activated Ha-ras into primary rat embryo fibroblasts.
      Surprisingly, using two different mutants we show that CDK4's ability to bind to
      p16INK4a and not its kinase activity is important for its transforming potential.
      In addition, p16INK4a but not a mutant form that is found in human tumours can
      completely abrogate focus formation by CDK4 suggesting that CDK4 can malignantly
      transform cells by sequestering p16INK4a or other CKIs. We demonstrate that both
      cyclin D1 and CDK4 functionally depend on active Myc to exert their potential as
      oncogenes and vice versa that the transforming ability of Myc requires functional
      cyclin D/CDK complexes. Moreover, we find that p16INK4a and the Rb related
      protein p107 which releases Myc after phosphorylation by cyclin D1/CDK4
      efficiently block Myc's activity as a transcriptional transactivator and as an
      oncogene. We conclude that both p16INK4a and cyclin D/CDK4 complexes are upstream
      regulators of Myc and directly govern Myc function in transcriptional
      transactivation and transformation via the pocket protein p107.

PMID- 9244354
TI  - Myb binding sites within the N-ras promoter repress transcription.
AB  - In vitro and in vivo methods were combined to determine the function of the three
      Myb binding sites (NrasI, NrasII and NrasIII) within the promoter region of the
      mouse N-ras gene. We found that the c-Myb DNA-binding domain can bind with high
      affinity to NrasI and NrasII, but with a reduced affinity to NrasIII. In
      contrast, the full length v-Myb protein from BM2 cells only bound to the middle
      one of the three sites, NrasII. Both c-Myb and v-Myb functioned as repressors and
      reduce the basal activity of the N-ras promoter by 60%, as determined by
      transient transfection experiments using different regions of the N-ras promoter.
      This repression required a functional Myb DNA-binding domain and could not be
      overcome by fusion to the potent VP16 activation domain. In electrophoretic
      mobility shift assays, the v-Myb protein is shown to be present in different
      conformations depending on its binding to the NrasII or the mim-1A site. The v
      Myb conformation is thus suggested to play a critical role in the regulation of v
      Myb activity.

PMID- 9244355
TI  - Expression of the p16INK4a tumor suppressor versus other INK4 family members
      during mouse development and aging.
AB  - Four INK4 proteins can prevent cell proliferation by specifically inhibiting
      cyclin D-dependent kinases. Both p18INK4c and p19INK4d were widely expressed
      during mouse embryogenesis, but p16INK4a and p15INK4b were not readily detected
      prenatally. Although p15INK4b, p18INK4c and p19INK4d were demonstrated in many
      tissues by 4 weeks after birth, p16INK4a protein expression was restricted to the
      lung and spleen of older mice, with increased, more widespread mRNA expression
      during aging. Transcripts encoding the INK4a alternative reading frame product
      p19ARF were not detected before birth but were ubiquitous postnatally. Expression
      of p16INK4a and p15INK4b was induced when mouse embryos were disrupted and
      cultured as mouse embryo 'fibroblasts' (MEFs). The levels of p16INK4a and
      p18INK4c, but not p15INK4b or p19INK4d, further increased as MEFs approached
      senescence. Following crisis and establishment, three of four independently
      derived cell lines became polyploid and expressed higher levels of functional
      p16INK4a. In contrast, one MEF line that sustained bi-allelic deletions of INK4a
      initially remained diploid. Therefore, loss of p16INK4a and other events
      predisposing to polyploidy may represent alternative processes contributing to
      cell immortalization. Whereas p18INK4c and p19INK4d may regulate pre- and
      postnatal development, p16INK4a more likely plays a checkpoint function during
      cell senescence that underscores its selective role as a tumor suppressor.

PMID- 9244356
TI  - The chicken adenosine receptor 2B gene is regulated by v-myb.
AB  - The retroviral oncogene v-myb is a mutated and truncated version of the c-myb
      proto-oncogene and encodes a transcription factor (v-Myb) that specifically
      transforms myelomonocytic cells. v-Myb is thought to transform myelomonocytic
      cells by affecting the expression of specific target genes, most of which as yet
      remain unknown. To identify novel v-Myb regulated genes we have employed
      'differential display', using a myelomonocytic chicken cell line that expresses a
      conditional version of v-Myb. Here we describe the identification of the gene
      encoding the A2b adenosine receptor, a member of the seven transmembrane receptor
      superfamily, as a v-Myb target gene. Our results provide the first evidence that
      v-Myb directly regulates a gene encoding a membrane receptor and establish a link
      between Myb function and adenosine receptor signaling.

PMID- 9244357
TI  - c-Jun involvement in vitamin E succinate induced apoptosis of
      reticuloendotheliosis virus transformed avian lymphoid cells.
AB  - Previous studies have shown that treatment of avian reticuloendotheliosis virus
      transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells with 10 microg/ml (18.8
      microM) of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for 3 days
      induced approximately 50% of the cells to undergo apoptosis. Elevated and
      prolonged expression of c-jun mRNA and protein was temporally correlated with VES
      induced cell death. Data presented in this paper show that the elevated and
      prolonged expression of c-jun message and protein are not accounted for by
      enhanced stability, and show the involvement of c-Jun in VES-induced apoptosis in
      this lymphoblastoid cell type. C4-1 cells infected with a virus carrying a
      dominant, negatively acting mutant form of c-Jun, supjun-1, exhibited: (i) 71%
      reduction in VES-induced apoptosis, (ii) a 2.0-2.5-fold decrease in wildtype,
      endogenous c-Jun expression, and (iii) a 2.4-2.6-fold reduction in AP-1 binding
      activity. Additionally, cells co-treated with VES plus RRR-alpha-tocopherol,
      exhibited a 70% reduction in apoptosis, a marked reduction in c-Jun expression
      and a 1.6-fold reduction in AP-1 binding activity. These studies suggest that c
      Jun plays a crucial role in VES-induced apoptosis in C4-1 cells, and add to our
      understanding of mechanisms of action involved in VES-mediated tumor cell growth
      inhibition.

PMID- 9244358
TI  - The p19INK4D cyclin dependent kinase inhibitor gene is altered in osteosarcoma.
AB  - Inhibition of cyclin dependent kinases (CDK) by cyclin dependent kinase
      inhibitors (CDKI) blocks cell cycle progression and inhibits cellular
      proliferation. The archetypical member of the INK4 CDKI family, p16INK4A (also
      called CDKN2), is a tumor suppressor frequently deleted or mutated in certain
      neoplasms and many cell lines. Because p19INK4D has strong structural and
      functional similarity to p16INK4A, we have assessed its role as a tumor
      suppressor. This was accomplished by screening the p19INK4D coding region for
      mutations, deletions and rearrangements in sarcomas and non-small cell lung
      cancers. Alterations of the p19INK4D gene were found in samples from five of 67
      (7%) patients with osteosarcomas and none were found in other types of sarcomas
      or in lung cancers. Five osteosarcoma samples had Southern blot patterns
      consistent with gene rearrangement. These samples included a primary and
      recurrent osteosarcoma from the same patient; both with the same rearrangement.
      Four samples had SSCP patterns consistent with sequence alterations, sequencing
      determined that three were due to silent base changes and apparently
      polymorphisms. Sequencing the fourth shifted band revealed a one base insertion
      causing a frameshift beginning with codon 27. In summary, these studies found
      alterations affecting the p19INK4D gene in a small but significant number of
      osteosarcomas. Presumably, abnormalities of this gene contribute to the
      development of cancer of bone cells.

PMID- 9244359
TI  - Protein interactions at the carboxyl terminus of p53 result in the induction of
      its in vitro transactivation potential.
AB  - The tumor suppressor protein p53 is a transcription factor frequently inactivated
      in human cancers. We have studied the DNA binding potential and the
      transcriptional activity of p53 variants and p53 protein complexes in in vitro
      transcription assays. p53 specific transcription was measured via introduction of
      radioactive UTP into G-free cassette transcripts regulated by promoter sequences
      containing p53 response elements. Latent and activated p53 fractions were
      prepared from insect cells infected with p53 encoding baculoviruses by
      chromatography on heparin columns. p53 fractions distinguishable by their
      specific DNA binding activities and their recognition by monoclonal antibody
      PAb421 were obtained. Specific DNA binding and binding to PAb421 are mutually
      exclusive. The C-terminus of p53 can be phosphorylated by casein kinase II,
      protein kinase C and cyclin dependent kinases. The antibody PAb421 binds within
      the PKC phosphorylation site of p53 and is able to activate DNA binding of latent
      p53 in vitro. Activation of p53 by PAb421 also results in enhanced
      transactivation in vitro. Dephosphorylation of latent p53 with phosphatase 2A
      does not change these properties. This suggests that a conformational change in
      the carboxyl terminal domain of p53 controls the transactivation potential of
      p53.

PMID- 9244360
TI  - IP6: a novel anti-cancer agent.
AB  - Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM
      concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as
      inositol (Ins) are contained in most mammalian cells, wherein they are important
      in regulating vital cellular functions such as signal transduction, cell
      proliferation and differentiation. A striking anti-cancer action of IP6 has been
      demonstrated both in vivo and in vitro, which is based on the hypotheses that
      exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5),
      and inhibit cell growth. There is additional evidence that Ins alone may further
      enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation,
      IP6 also causes differentiation of malignant cells often resulting in a reversion
      to normal phenotype. These data strongly point towards the involvement of signal
      transduction pathways, cell cycle regulatory genes, differentiation genes,
      oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti
      neoplastic action of IP6.

PMID- 9244361
TI  - Effects of clobenpropit (VUF-9153), a histamine H3-receptor antagonist, on
      learning and memory, and on cholinergic and monoaminergic systems in mice.
AB  - The effects of clobenpropit (VUF-9153), a potent histamine H3-receptor
      antagonist, on a scopolamine-induced learning deficit in the step-through passive
      avoidance test was studied in mice. Clobenpropit (10 and 20 mg/kg) alone showed a
      tendency to ameliorate the scopolamine-induced learning deficit, and clobenpropit
      (10 mg/kg) in combination with zolantidine (20 mg/kg), a histamine H2-receptor
      antagonist, ameliorated the scopolamine-induced effect. This ameliorating effect
      was antagonized by (R)-alpha-methylhistamine (20 mg/kg), a histamine H3-receptor
      agonist and pyrilamine (20 mg/kg), a histamine H1-receptor antagonist, suggesting
      that clobenpropit in combination with zolantidine showed the ameliorating effect
      via histamine H3 receptors and/or histamine H1 receptors. We also studied the
      effects of clobenpropit on cholinergic and monoaminergic systems. Clobenpropit
      did not show any significant effect on these neuronal systems except the
      activation of noradrenergic system. The present results suggest that the effect
      of clobenpropit might be partially involved with the activation of noradrenergic
      system, and the histaminergic system may play certain important roles in learning
      and memory.

PMID- 9244362
TI  - Identification of [Met5]-enkephalin in developing, adult, and renewing tissues by
      reversed-phase high performance liquid chromatography and radioimmunoassay.
AB  - Extracts of adult corneal epithelium, and developing and adult cerebellum, aorta,
      and heart, from rats were evaluated for [Met5]-enkephalin. Samples were prepared
      by ultrafiltration and solid phase extraction with a C-18 Sep-pak, separated by
      reversed phase high-performance liquid chromatography, and analyzed by
      radioimmunoassay (RIA). This qualitative analysis revealed the presence of [Met5]
      enkephalin in all tissues but the adult cerebellum. These results confirm and
      extend earlier reports that have used RIA or immunohistochemistry with regard to
      the presence of this opioid peptide in developing and renewing tissues, and
      indicate that [Met5]-enkephalin is indeed being recognized by immunological
      assays.

PMID- 9244363
TI  - Effects of buspirone on dopaminergic supersensitivity.
AB  - The effects of buspirone treatment on dopaminergic supersensitivity induced by
      long-term haloperidol administration were studied; both spontaneous activity
      (locomotion and rearing frequencies) of rats observed in an open-field and
      apomorphine-induced stereotypy were used as experimental parameters. Buspirone
      per se (3.0 mg/kg, twice daily, for 30 days) did not produce dopaminergic
      supersensitivity. When buspirone was given in combination to haloperidol (2.0
      mg/kg, once daily, for 30 days), it decreased the neuroleptic withdrawal symptoms
      as detected in open-field behavior but not in apomorphine-induced stereotypy.
      Although single administration of buspirone per se decreased both open-field and
      apomorphine-induced stereotypy behavior, buspirone single administration did not
      modify the acute effects of haloperidol on these two behavioral models. Taken
      together with previous behavioral results showing that buspirone reverses
      haloperidol-induced catalepsy, the present data suggest that buspirone co
      administration may lead to important clinical advantages concerning different
      extrapyramidal side effects of neuroleptic treatment.

PMID- 9244364
TI  - Inhibitory effects of jasmine green tea epicatechin isomers on free radical
      induced lysis of red blood cells.
AB  - Jasmine green tea is an excellent source of natural polyphenol antioxidants
      including mainly (-) epicatechin (EC), (-) epicatechin gallate (ECG), (-)
      epigallocatechin (EGC) and (-) epigallocatechin gallate (EGCG). The present study
      was to test our hypothesis that ingestion of jasmine tea would protect red blood
      cell (RBC) membrane from free radical-induced oxidation if jasmine tea
      epicatechin isomers could be absorbed and circulated in blood. When incubated
      with RBC suspension, all four epicatechin isomers purified from jasmine tea
      exhibited a strong protection for RBC membrane to hemolysis induced by 2,2'-azo
      bis(2-amidinopropane) dihydrochloride (AAPH), an azo free radical initiator. The
      inhibitory effect was dose-dependent at the concentrations of 2.5 microM to 40
      microM. The fatty acid analysis revealed that all four epicatechin isomers
      significantly prevented loss of arachidonic acid (20:4n-6) and docosahexaenoic
      acid (22:6n-3) in RBC incubated under the same conditions. Although the in vitro
      antioxidative activity of EGCG and ECG was more effective than EGC and EC, the
      latter two isomers were more important in vivo in scavenging free radicals. This
      was because only EGC and EC instead of EGCG and ECG were circulating in blood
      stream after a gavage-dose of 100 mg jasmine tea GTP mixture. In fact, ingestion
      of jasmine tea GTP extracts was associated with a significant decrease in
      susceptibility of RBC to hemolysis in rats.

PMID- 9244365
TI  - Majonoside-R2 reverses social isolation stress-induced decrease in pentobarbital
      sleep in mice: possible involvement of neuroactive steroids.
AB  - Majonoside-R2 (MR2) is a major ocotillol-type saponin constituent of Vietnamese
      ginseng. We investigated the effect of MR2 on the social isolation stress-induced
      decrease in pentobarbital sleep in mice, and elucidated the possible involvement
      of neurosteroidal sites of the GABA(A) receptor complex in the pharmacological
      activity of MR2. MR2 (3.1-6.2 mg/kg, i.p. or 5-10 microg, i.c.v.) dose
      dependently reversed the decrease in pentobarbital sleep caused by social
      isolation stress to the level of sleep in the group-housed mice, but it had no
      effect on pentobarbital sleep in group-housed mice.
      Allotetrahydrodeoxycorticosterone (5alpha-pregnane-3alpha,21-diol-20-one, allo
      THDOC; 12.5 microg, i.c.v.), the positive allosteric modulator of the GABA(A)
      receptor, and alpha-helical CRF(9-41) (alpha hCRF; 25 microg, i.c.v.), the
      corticotropin-releasing factor (CRF) antagonist, also reversed the decrease in
      pentobarbital sleep caused by social isolation stress. The reversing effects of
      i.c.v. MR2 and i.c.v. allo-THDOC on the decrease in pentobarbital sleep in
      isolated mice were significantly attenuated by pregnenolone sulfate (10 microg,
      i.c.v.), the steroidal negative allosteric modulator of the GABA(A) receptor. In
      contrast, when injected i.c.v., MR2, as well as allo-THDOC and alpha hCRF,
      significantly reversed the decrease in pentobarbital sleep induced by
      pregnenolone sulfate (10 microg, i.c.v.) and CRF (10 microg, i.c.v.) in group
      housed mice. These results suggest that the reversing effect of MR2 on the social
      isolation stress-induced decrease in pentobarbital sleep is mediated by the
      neurosteroid site on the GABA(A) receptor complex in mice.

PMID- 9244366
TI  - Reduced glutathione inhibits rabbit and rat skeletal muscle lactate dehydrogenase
      and prevents dinitrophenol induced extracellular acidification by an epithelial
      cell line.
AB  - Glutathione (GSH) is a tripeptide synthesised enzymatically from its components
      amino-acids by unicellular and multicellular organisms. GSH acts as a cellular
      anti-oxidant, protects the structural configuration of some enzymes, is involved
      in erythrocyte function and plays a role as co-enzyme in several reactions. We
      have found that GSH inhibits purified lactate dehydrogenase (1.56 U LDH/ml) from
      rabbit skeletal muscle after 6 min pre-incubation with an ED50 of about 5.4
      microM. The inhibition is time dependent with a maximum after 45 minutes pre
      incubation. Buffer (5 x 10(-2) M TRIZMA hydrochloride, pH 7.4) and a chelator (2
      x 10(-3) M EDTA) in the pre-incubation solution did not prevent the inhibition.
      Prolonged dialysis was almost without effect on GSH-inhibited LDH activity
      solution, indicating either an irreversible or a very tight binding inhibition.
      Kinetic analysis showed that this inhibition is of a very tight binding and at
      the same time of the uncompetitive type. GSH also inhibits LDH activity of rat M.
      soleus and M. gastrocnemius homogenates. This effect is probably unrelated to the
      reducing property of GSH since dithioerythritol (0.17-1.34 mM) does not mimic it.
      Loading of MDCK cells with glutathione ethylester completely prevented the
      acidification induced by 2,4-dinitrophenol, suggesting that GSH may influence the
      glycolytic pathway in vivo.

PMID- 9244368
TI  - Differences in the change in the time course of plasma endothelin-1 and
      endothelin-3 levels after exercise in humans. The response to exercise of
      endothelin-3 is more rapid than that of endothelin-1.
AB  - Several studies have indicated that endothelin-1 (ET-1) and endothelin-3 (ET-3)
      are produced by different cells. Although ET-1 is produced by vascular
      endothelial cells, these cells do not produce ET-3. The presence of ET-3 in the
      brain of several species suggests that ET-3 is a novel neuropeptide. It is
      unclear whether there are differences in the release of ET-1 and ET-3 under
      various physiological conditions in humans. In the present study, we measured the
      plasma concentrations of both ET-1 and ET-3 before and after endurance exercise
      on a cycle ergometer. Male athletes exercised on a cycle ergometer for 30 min at
      intensity of 130% of their individual ventilatory threshold (VT), which is
      intense exercise. Plasma ET-1 and ET-3 were greatly elevated by exercise, but
      there was a marked difference in the time-course of the change in plasma
      concentration between the two peptides. The level of ET-1 peaked 30 min after
      exercise, whereas that of ET-3 peaked immediately after exercise. Thus, plasma ET
      3 increased faster than plasma ET-1 after exercise. The exercise-induced change
      in the time course in plasma ET-3, but not in ET-1, is similar to that in plasma
      norepinephrine which is a neurotransmitter, suggesting that the rapid elevation
      in plasma ET-3 is partly attributable to the neuronal response to exercise. The
      observed difference in the change in the time course of plasma ET-1 and ET-3
      levels suggests that the mechanisms by which exercise alters the release and/or
      synthesis of these two peptides differ.

PMID- 9244367
TI  - Binding affinity of proteins to hsp90 correlates with both hydrophobicity and
      positive charges. A surface plasmon resonance study.
AB  - The 90 kDa heat shock protein (hsp90) is a major cytoplasmic molecular chaperone
      associating with numerous other proteins including steroid receptors. Here we
      provide the first numerical analysis of hsp90-target associations using surface
      plasmon resonance. Binding affinities of histones, the "native molten globule",
      casein and calmodulin to hsp90 decrease in the order of Kd = 70 +/- 24, 220 +/-
      70 and 1800 +/- 600 nM, respectively. Analysis of the structure of binding
      proteins revealed that their binding affinity depends on both hydrophobicity and
      positive charges making the discriminative features of hsp90 similar to those of
      other molecular chaperones.

PMID- 9244370
TI  - Decreased total antioxidant capacity and elevated lipid hydroperoxide
      concentrations in sera of epileptic patients receiving phenytoin.
AB  - Oxidative stress (free radical generation exceeds antioxidant defense) occurs in
      many diseases and after exposure to certain chemicals. We automated assays
      estimating the antioxidant status of serum and lipid hydroperoxide concentrations
      using the Syva-30R automated analyzer. In this assay, the antioxidant status of
      serum is measured by its ability to inhibit the generation of free radicals from
      2,2'-amino-di-[3-ethylbenzthiazole sulphonate] by metmyoglobin and hydrogen
      peroxide. The assay for measuring lipid hydroperoxide concentration in serum
      utilizes the ability of lipid hydroperoxide to generate methylene blue from 10N
      methylcarbamyl 3,7-dimethylamino 10H-phenothiazine. Phenytoin is known to
      initiate oxidative damage to proteins and lipids in murine maternal hepatic and
      embryonic tissue organelles. Therefore, we measured lipid hydroperoxide
      concentrations in sera of epileptic patients receiving phenytoin. We observed
      significantly elevated lipid hydroperoxide concentrations in epileptic patients
      receiving phenytoin compared to controls. The total antioxidant capacity of sera
      of epileptic patients was lower than the antioxidant capacity of control sera. We
      observed poor correlation between the serum lipid hydroperoxide concentration and
      triglyceride or cholesterol concentration in epileptic patients. We conclude that
      lipid hydroperoxide concentrations were elevated in sera of epileptic patients.

PMID- 9244369
TI  - Involvement of supraspinal GABA receptors in majonoside-R2 suppression of
      clonidine-induced antinociception in mice.
AB  - Majonoside-R2 (MR2) is a major constituent of Vietnamese ginseng (Panax
      vietnamensis, Ha et Grushv. Araliaceae) that is known to exhibit antagonistic
      activity against opioid-induced antinociception. In this study, we investigated
      the effect of MR2 on the antinociception caused in mice by the alpha2
      adrenoceptor agonist clonidine, and elucidated the role of supraspinal GABAergic
      systems in this effect of MR2. The systemic administration of clonidine (0.5-2.5
      mg/kg, s.c.) dose-dependently suppressed the nociceptive response of mice in the
      tail-pinch and hot-plate tests. The intraperitoneal (i.p.),
      intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of idazoxan
      (a selective alpha2-adrenoceptor antagonist) significantly antagonized the
      antinociceptive effect of clonidine in both tests. MR2 administered systemically
      (1.5-6.2 mg/kg, i.p.) or centrally (5-10 microg/mouse, i.c.v. or i.t.) dose
      dependently antagonized the clonidine (1 mg/kg, s.c.)-induced antinociception in
      the tail-pinch test but not in the hot-plate test. The antagonistic effect of
      i.c.v. MR2 on the systemic clonidine-induced antinociception in the tail-pinch
      test was significantly reversed by i.c.v. administrations of the selective
      benzodiazepine receptor antagonist flumazenil (5 microg/mouse) and the GABA(A)
      antagonist picrotoxin (0.25 microg/mouse). These results suggest that the
      supraspinal GABA(A)/benzodiazepine receptors are involved in the antagonistic
      effect of MR2 on the clonidine-induced antinociception in the tail-pinch test in
      mice.

PMID- 9244371
TI  - Oxygenation capacity of hypotonized and crosslinked rat erythrocytes.
AB  - Rat erythrocytes subjected to hypotonic-isotonic dialysis, or crosslinking with
      bifunctional reagents (glutaraldehyde and dimethyl suberimidate hydrochloride)
      show a high percentage of methemoglobin and decreased oxyhemoglobin content which
      implies a low oxygen carrying capacity. Such modified cells maintain reversible
      oxygen binding properties although, they present a high hemoglobin oxygen
      affinity (low P50) and a diminished cooperativity in binding oxygen to hemoglobin
      (low n). These results suggest a reduced capacity of liberating oxygen to tissues
      under low PO2. Changes produced in erythrocytes can not be restored even in the
      presence of energy (ATP), reduced glutathione and 2,3-bisphosphoglyceric acid
      during the dialysis process or after crosslinking/permeabilizing treatment.

PMID- 9244372
TI  - Reduction of insulin resistance attenuates the development of hypertension in
      sucrose-fed SHR.
AB  - We examined the effect of pioglitazone, a thiazolidinedione derivative that
      increases insulin sensitivity without increasing insulin secretion, on the
      development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old
      male SHR received 12% sucrose dissolved in tap water as drinking water. For 5
      weeks, half of the rats were given regular rat chow, and the rest were fed with
      rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma
      insulin levels were examined before and after oral glucose administration by
      gavage. Sucrose treatment elicited a significant elevation of systolic blood
      pressure 3 weeks after the beginning of treatment; pioglitazone treatment
      attenuated this elevation. The insulin resistance and hyperinsulinemia observed
      in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone
      treatment also significantly reduced the urinary excretion of catecholamines and
      plasma renin activity, both of which were significantly greater in sucrose-fed
      SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone
      treatment also attenuated the development of hypertension in SHR fed the regular
      rat chow, but not in WKY rats. These results indicate that insulin resistance and
      hyperinsulinemia play an important role in the development of hypertension in SHR
      probably through the activation of the renin-angiotensin system and sympathetic
      nervous outflow. This study also shows that chronic sucrose treatment exacerbated
      the development of hypertension through these mechanisms, precipitating insulin
      resistance.

PMID- 9244373
TI  - Dual actions of (-)-stepholidine on the dopamine receptor-mediated adenylate
      cyclase activity in rat corpus striatum.
AB  - (-)-Stepholidine (SPD) is an antagonist of normosensitive dopamine (DA)
      receptors, but it exhibits D1 agonistic action on rotational behaviour in rats
      with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars
      compacta (SNC). In the present study, agonistic and antagonistic effects of SPD
      on the DA receptor-mediated synaptosomal adenylate cyclase (AC) activity in rat
      striatum were investigated. After blockade of D2 receptors, SPD augmented AC
      activity dose-dependently. The EC50 value was 41.1 +/- 8.6 micromol/L. At the
      concentration of 10 micromol/L, SPD increased cAMP formation from a basal level
      (50.8 +/- 10.3 pmol/mg protein/min) to 133.7 +/- 31.8 pmol/mg protein/min. The
      SPD-induced stimulation of AC activity was almost completely reversed by 10
      micromol/L Sch23390. These results indicate that SPD possesses an agonistic
      action on the D1 receptor. Forskolin-stimulated adenylate cyclase (FSAC) activity
      was used as a model to elucidate the effect of SPD on D2 receptors. The results
      indicate that DA inhibited FSAC activity dose-dependently, while SPD partially
      restored FSAC activity. Taken together, these results support the conclusion that
      SPD has dual actions on DA receptors that mediate AC activity, i.e., an agonistic
      action on D1 receptors and an antagonistic action on D2 receptors.

PMID- 9244374
TI  - delta-9-Tetrahydrocannabinol increases prodynorphin and proenkephalin gene
      expression in the spinal cord of the rat.
AB  - Hypoalgesia induced by cannabinoid drugs has been found to implicate the opioid
      system. The effect of five days treatment with delta-9-tetrahydrocannabinol (THC)
      was examined on prodynorphin (PDYN) and proenkephalin (PENK) gene expression in
      the spinal cord of male rats. PDYN and PENK gene expression was estimated
      measuring by northern blot analysis mRNA levels in the whole spinal cord,
      containing perikarya of these neurons. The subchronic treatment with THC (5
      mg/kg/day; 5 days; i.p.) produced an increase in PDYN (39%) and PENK (34%) gene
      expression when compared with the vehicle treated group. These results suggest
      that the effects of THC in the spinal cord involve an increase in opioid
      activity, and therefore sustain the hypothesis of an interaction between the
      cannabinoid and opioid systems in this region.

PMID- 9244375
TI  - Involvement of a 50-kDa mRNP protein from Saccharomyces cerevisiae in mRNA
      binding to ribosomes.
AB  - A yeast 50-kDa mRNA-binding protein (50mRNP) is found selectively associated with
      the 48S and 80S initiation complexes. This protein is structurally related to the
      translational elongation factor EF-1alpha. The protein reacts with antibodies
      directed against EF-1alpha and, similarly, EF-1alpha recognizes antibodies
      against the 50mRNP protein. This is evidence that they share at least one epitope
      which allows a similar antigenic behavior. In addition, both proteins show
      similar cleavage patterns upon treatment with the endoproteinase Lys-C. A murine
      antibody raised against 50mRNP inhibits both 48S and 80S initiation complex
      formation. The inhibitory effect is relieved by preincubating anti-50mRNP with EF
      1alpha. Antibody to EF-1alpha manifests a similar inhibitory pattern for the
      formation of 48S and 80S complexes. These data strongly suggest that 50mRNP is an
      EF-1alpha-like polypeptide essential for the formation of the above complexes.

PMID- 9244376
TI  - Molecular cloning of cDNA for guinea pig CYP1A2 comparison with guinea pig
      CYP1A1.
AB  - Guinea pig CYP1A2 cDNA was isolated by RT-PCR from liver tissue of 3,3'
      methylcholanthrene-treated guinea pigs. It shares considerable sequence identity
      with guinea pig CYP1A1 (nt 77%, aa 65%), but differs in levels of constitutive
      expression, function, and inducibility. Western blot analysis of protein
      expressed by full-length cDNA in COS-1 cells identified CYP1A2 (56 kDa) and
      CYP1A1 (53 kDa) proteins in corun liver microsomes. CYP1A2 transfectants
      metabolized methoxyresorufin and ethoxyresorufin, while CYP1A1 transfectants
      metabolized only ethoxyresorufin. Constitutive expression of CYP1A2 mRNA (2.0 kb)
      and protein was much lower than that of CYP1A1 mRNA (2.6 kb) and protein, but the
      fold induction of CYP1A2 by 3,3'-methylcholanthrene was greater than that of
      CYP1A1. Changes in splicing of CYP1A2 pre-mRNA occur upon treatment with 3,3'
      methylcholanthrene.

PMID- 9244377
TI  - Substrates for protein kinase CK2 in insulin receptor preparations from rat liver
      membranes: identification of a 210-kDa protein substrate as the dimeric form of
      endoplasmin.
AB  - Chromatography of extracts from rat liver membranes on wheat-germ lectin
      Sepharose resulted in a partial resolution of the insulin receptor from other
      phosphorylatable proteins. Among the latter, a protein (p210, with an apparent
      M(r) of 210 kDa on SDS/PAGE under nonreducing conditions) was found to be
      phosphorylated by protein kinase CK2 on Thr and Ser residues. Under reducing
      conditions p210 was resolved into two phosphopolypeptides with apparent M(r) of
      95 and 105 kDa. Neither the 95-kDa nor the 105-kDa polypeptides were recognized
      by antibodies against the beta-subunit of the insulin receptor. Both polypeptides
      gave identical phosphopeptide maps after protease V8 digestion and contained the
      same N-terminal amino acid sequence. This sequence coincided with that of
      endoplasmin, and both polypeptides as well as p210 were recognized by antibodies
      against this protein. This shows that p210 corresponds to the dimeric form of rat
      liver endoplasmin. DEAE-Sepharose chromatography of p210 preparations removed
      most other contaminating proteins and revealed the presence of a protein kinase
      activity that coeluted with p210. This protein kinase possessed the properties
      (substrate specificity and inhibition by heparin) that are characteristic of the
      protein kinase CK2 enzymes. Furthermore, phosphoamino acid analysis and
      phosphopeptide maps of the 95/105-kDa polypeptides phosphorylated either by the
      endogenous protein kinase or by exogenous protein kinase CK2 gave similar
      results. The phosphorylation of p210/endoplasmin by protein kinase CK2 and its
      coelution gives support to the involvement of this protein kinase in membrane
      associated processes.

PMID- 9244378
TI  - Protein modification by methylglyoxal: chemical nature and synthetic mechanism of
      a major fluorescent adduct.
AB  - The nonenzymatic Maillard reaction of proteins, initiated by the addition of
      sugars and other aldehydes and ketones, is thought to be an important mechanism
      in aging and the pathogenesis of diabetic complications. The alpha-dicarbonyl
      compounds are considered to be key intermediates in this reaction. Methylglyoxal
      (MG) (pyruvaldehyde), a physiological alpha-dicarbonyl compound, has been shown
      to modify proteins both in vitro and in vivo. Here we describe a novel
      fluorescent pyrimidine, N-delta-(5-hydroxy-4,6-dimethylpyrimidine-2-yl)-L
      ornithine (argpyrimidine), formed from the Maillard reaction of MG with N-alpha-t
      BOC-arginine. We find that the fluorescence spectrum of argpyrimidine is similar
      to that of methylglyoxal-modified proteins, suggesting that it is a major product
      in such modified proteins. HPLC-quantification of argpyrimidine in proteins
      incubated with methylglyoxal revealed a time-dependent formation. We detected
      significant amounts of argpyrimidine in incubations of N-alpha-t-BOC-arginine
      with micromolar concentrations of MG, and we find that various sugars and
      ascorbic acid serve as precursors. Our studies indicate that argpyrimidine is
      synthesized through an intermediate 3-hydroxypentane-2,4-dione and provide a
      chemical basis for fluorescence in proteins modified by methylglyoxal. We suggest
      that enhanced intrinsic fluorescence in diabetic proteins may be due, in part, to
      methylglyoxal-mediated Maillard reactions.

PMID- 9244379
TI  - Arginase of Bacillus brevis Nagano: purification, properties, and implication in
      gramicidin S biosynthesis.
AB  - An arginase [EC 3.5.3.1] was purified to homogeneous state from a gramicidin S
      producing Bacillus brevis Nagano. The enzyme has a molecular weight of about
      180,000 on gel filtration. The subunit molecular weight is 32,000 by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis, indicating that the enzyme is
      hexameric. The optimum pH is found near 10.0. Mn2+ is essential for its activity
      and Fe2+, Co2+, Ni2+, and Mg2+ cannot replace Mn2+. The enzyme is highly specific
      for L-arginine with a K(m) value of 12.8 mM for L-arginine, which is similar to
      that of liver-type arginase in ureotelic animals. B. brevis arginase is
      apparently induced by the addition of L-arginine to the glutamate medium. The
      increased formation of L-ornithine, a constituent amino acid of gramicidin S, by
      arginase may be involved in the accelerated production of gramicidin S by B.
      brevis in the presence of L-arginine in the growth medium.

PMID- 9244380
TI  - Elongation factor Ts of Chlamydia trachomatis: structure of the gene and
      properties of the protein.
AB  - A putative structural gene cluster containing four open reading frames (ORFs)
      located downstream of the omp1 gene of Chlamydia trachomatis mouse pneumonitis
      (MoPn) was cloned and sequenced. A GenBank survey indicated that the identified
      cluster is similar to the rpsB-tsf-pyrH(smbA)-frr region of Escherichia coli. The
      second ORF was 846 bp encoding a 282-amino-acid polypeptide with a calculated
      M(r) 30,824. Alignment of this deduced protein sequence and E. coli elongation
      factor Ts (EF-Ts, product of tsf) demonstrated 34% identity and an additional 14%
      similarity. The putative chlamydial tsf gene was expressed in E. coli as a
      nonfusion protein and as a 6x His-tagged fusion protein. By SDS-PAGE analysis,
      the molecular weights of the nonfusion recombinant protein and a protein of
      chlamydial elementary bodies (EBs), which was recognized by monoclonal antibodies
      derived from the nonfusion recombinant protein, are 34 kDa. The purified
      recombinant 6x His-tagged fusion protein increased the rate of GDP exchange with
      both Chlamydia and E. coli elongation factor Tu (EF-Tu). These data show that the
      second gene of the identified cluster is tsf. Unlike EF-Ts from any other
      species, its activity was comparable to that of E. coli EF-Ts in exchange
      reaction with E. coli EF-Tu.

PMID- 9244381
TI  - Metabolic effects of altering redundant targeting signals for yeast mitochondrial
      malate dehydrogenase.
AB  - Eukaryotic cells contain highly homologous isozymes of malate dehydrogenase which
      catalyze the same reaction in different cellular compartments. To examine whether
      the metabolic functions of these isozymes are interchangeable, we have altered
      the cellular localization of mitochondrial malate dehydrogenase (MDH1) in yeast.
      Since a previous study showed that removal of the targeting presequence from MDH1
      does not prevent mitochondrial import in vivo, we tested the role of a putative
      cryptic targeting sequence near the amino terminus of the mature polypeptide.
      Three residues in this region were changed to residues present in analogous
      positions in the other two yeast MDH isozymes. Alone, these replacements did not
      affect activity or localization of MDH1 but, in combination with deletion of the
      presequence, prevented mitochondrial import in vivo. Measurable levels of the
      resulting cytosolic form of MDH1 were low with expression from a centromere-based
      plasmid but were comparable to normal cellular levels with expression from a
      multicopy plasmid. The cytosolic form of MDH1 restored the ability of a deltaMDH1
      disruption strain to grow on ethanol or acetate, suggesting that mitochondrial
      localization of MDH1 is not essential for its function in the TCA cycle. This TCA
      cycle function observed for the cytosolic form of MDH1 is unique to that isozyme
      since overexpression of MDH2 and of a cytosolic form of MDH3 in a deltaMDH1
      strain failed to restore growth. Finally, only partial restoration of growth of a
      deltaMDH2 disruption mutant was attained with the cytosolic form of MDH1,
      suggesting that MDH2 may also have unique metabolic functions.

PMID- 9244382
TI  - The analysis of the electron transfer rate from steady-state fluorescence
      spectroscopy.
AB  - The feasibility of obtaining the electron transfer rate from steady-state
      fluorescence spectroscopy was investigated. Polymeric films with a fixed
      concentration of an electron donor molecule were studied as a function of an
      electron acceptor concentration. The transfer studied was from
      tetraphenylporphyrin to duroquinone in a polystyrene matrix. The data were
      analyzed according to Perrin model and the critical radius for electron transfer
      obtained was 7.1 A. There was an attempt to obtain the electron transfer rate
      from the nearest-neighbor and Inokuti-Hirayama models, but the parameters that
      define the rate could not be unequivocally determined.

PMID- 9244383
TI  - Serine phosphorylation of syndecan-2 proteoglycan cytoplasmic domain.
AB  - Protein kinase C (PKC) is involved in cell-matrix and cell-cell adhesion, and the
      cytoplasmic domain of syndecan-2 contains two serines (residues 197 and 198)
      which lie in a consensus sequence for phosphorylation by PKC. Other serine and
      threonine residues are present but not in a consensus sequence. We investigated
      phosphorylation of syndecan-2 cytoplasmic domain by PKC, using purified GST
      syndecan-2 fusion proteins and synthetic peptides corresponding to regions of the
      cytoplasmic domain. A synthetic peptide encompassing the entire cytoplasmic
      domain of syndecan-2 was phosphorylated by PKC with high affinity. Peptide
      mapping and substitution studies showed that both serines were phosphoacceptors,
      but each had slightly different affinity, with that of serine-197 being higher
      than serine-198. The efficiency of phosphorylation was concentration-dependent.
      At low concentrations, the cytoplasmic domain peptides were monomeric, with 2
      mol/mol serine phosphorylation. At higher concentrations, however, the peptides
      formed dimers, with only 0.5 mol/mol phosphorylation. Concentration-dependent
      dimerization was not altered by phosphorylation. Phosphorylation is, therefore,
      dependent on the conformation of syndecan-2 cytoplasmic domain, but does not
      affect its oligomeric status.

PMID- 9244384
TI  - A- and B-subunit variant distribution in the holoprotein variants of protein
      toxin abrin: variants of abrins I and III have constant toxic A subunits and
      variant lectin B subunits.
AB  - The cytotoxic lectin abrin shows more than 30 variant forms (R. Hegde, T. K.
      Maiti, and S. K. Podder, 1991, Anal. Biochem. 194, 101-109). The lectin B subunit
      as cause for variance in abrins I and III was detected by a combination of one-
      and two-dimensional electrophoresis and Western blotting. Intriguingly, in abrin
      I but not in abrin III, association of a single A subunit with the variant B
      subunits shifts the holoprotein pI toward the alkaline side indicating that the
      subunit association involves neutralization of few negative charges. The B
      subunit variants of abrins I and III overlap in their pI, and the A-subunit
      association gives the holoproteins a distinctness on isoelectric focusing gel.
      The results were also confirmed by analyzing the pH titration curves. These
      differences in the subunit association pattern between abrins I and III are in
      corroboration with the previously observed differences in the kinetics of protein
      synthesis inactivation and accessibility of the disulfide bridge to reducing
      agents in the presence or absence of putative receptor (R. Hegde, A. Karande, and
      S. K. Podder, 1993 Eur. J. Biochem. 215, 411-419). Further, the genetic origin of
      variance was confirmed by peptide mapping of the individual subunit variants.
      Considering a theoretical value of 0.1 to 0.2 pI/charge, a 15-17 charge
      difference could be predicted between the variants of two extreme pIs. The fact
      that the A subunits are not shared between the groups was taken to interpret that
      the protein synthesized as prepro form is processed posttranslationally and the
      processing takes place only after the disulfide bond formation between A and B
      subunits. The N-terminal 16 amino acids of A subunits of abrins I and III showed
      26% dissimilarity. The A subunits of abrins I and III did not react with
      concanavalin A, indicating that the heterogeneity in the molecular weight is
      because of differential processing but not because of glycosylation.

PMID- 9244385
TI  - Age-associated increase in ferritin content of male rat liver: implication for
      diquat-mediated oxidative injury.
AB  - Our previous studies in rat hepatocytes demonstrated an age-dependent increase in
      sensitivity to diquat-induced cytotoxicity, possibly as a result of increased
      iron availability. The present study was conducted to determine whether
      quantitative or qualitative changes in hepatic ferritin occur as a consequence of
      aging and whether diquat-mediated oxidation is intensified by elevated ferritin
      concentrations. Hepatic ferritins were isolated from male Fischer 344 rats ages
      5, 15, and 25 months. Age-associated increases were observed in amounts of
      ferritin protein and ferritin iron per gram of liver, but there were no
      differences in proportions of H to L subunits or in rates of diquat-mediated iron
      release. The consequences of a threefold increase in ferritin content for diquat
      mediated lipid peroxidation and protein carbonyl formation were examined in
      microsomal incubation systems. The addition of isolated rat liver ferritin
      augmented diquat-mediated oxidative damage in a time- and concentration-dependent
      manner, and the inclusion of deferoxamine completely inhibited the stimulation by
      ferritin. The results indicate that availability of ferritin iron is an important
      determinant of diquat-mediated oxidative injury and support the hypothesis that
      elevated hepatic ferritin content is responsible, at least in part, for the age
      associated enhancement of diquat-induced toxicity.

PMID- 9244386
TI  - Glycosylation of bile-salt-stimulated lipase from human milk: comparison of
      native and recombinant forms.
AB  - Bile-salt-stimulated lipase (BSSL) is an enzyme present in human milk. BSSL is
      important for fat digestion in infants. It contains one site for N-glycosylation
      and a serine/threonine-rich domain which is highly O-glycosylated. Both N- and O
      linked sugar chains were studied on native BSSL from three donors and compared to
      the glycosylation of recombinant BSSL produced in Chinese hamster ovary or mouse
      fibroblast (C-127) cell lines. The carbohydrate composition of oligosaccharides
      was mapped using sugar and methylation analyses, enzyme-linked immunosorbant
      assay, and different separation techniques. Native BSSL was found to be highly
      glycosylated (19-26%). It contained a high amount of fucosylated oligosaccharides
      and expressed both Lewis a and Lewis b blood group antigens. None of the
      recombinant BSSL forms contained fucose. N-linked structures on native BSSL were
      identified as mainly mono- and disialylated biantennary complex type structures
      with or without fucose substitution. High-pH anion-exchange chromatography
      analysis indicated that the recombinant forms of BSSL contained similar types of
      N-glycan structures differing mainly in their content of sialic acid and by the
      absence of fucose residues. Native BSSL contained predominantly large O-linked
      oligosaccharides. This was in contrast to the recombinant forms of BSSL which
      contained mainly short type O-glycans with a high content of sialic acid.
      Interestingly, the estimated number of O-glycans attached to native BSSL was
      lower than that for the recombinant forms.

PMID- 9244387
TI  - Disulfide structure of the heparin binding domain in vascular endothelial growth
      factor: characterization of posttranslational modifications in VEGF.
AB  - Preparations of recombinant human vascular endothelial growth factor (VEGF165)
      expressed in Chinese hamster ovary (CHO) cells and Escherichia coli were compared
      using a variety of analytical methods. Amino terminal sequence analyses of both
      the CHO- and E. coli-derived VEGF165 confirmed the predicted amino terminal
      sequence for VEGF165, although the CHO VEGF165 exhibited a heterogeneous amino
      terminus with sequences beginning at Ala-1 (76%), Pro-2 (4%), Ala-4 (13%), and
      Glu-5 (7%). Tryptic digests of reduced and carboxymethylated CHO- and E. coli
      derived VEGF165 were examined by LC/MS analyses, indicating equivalent primary
      structure, except for the glycosylation at Asn-75 in the CHO-derived VEGF165. The
      N-linked carbohydrate in the CHO-derived VEGF165 was determined to be a complex
      fucosylated biantennary structure. The data obtained from LC/MS analysis and
      amino terminal sequence analysis of VEGF165 confirmed 98% of the primary
      structure. Disulfide linkages for the eight cysteine residues in the carboxyl
      terminal heparin binding domain were assigned by amino terminal sequencing of
      fragments produced by tryptic digests of each native molecule. The following
      disulfides have been identified for both CHO- and E. coli-derived VEGF165: Cys
      117 and Cys-135, Cys-120 and Cys-137, Cys-139 and Cys-158, plus Cys-146 and Cys
      160. Plasmin cleavage of VEGF165 yields an N-terminal homodimeric VEGF110 and a
      55-amino-acid carboxyl terminal domain. VEGF110 was resistant to further
      proteolytic or chemical digestion such that the disulfide linkages were not
      elucidated. The 55-amino-acid carboxyl terminal region of VEGF165 appears to be a
      unique heparin binding domain with no known protein homology.

PMID- 9244388
TI  - Factors affecting the permeability of Pseudomonas aeruginosa cell walls toward
      lipophilic compounds: effects of ultrasound and cell age.
AB  - The objective of this research was to elucidate the factors effecting the
      permeability of cell membranes of gram-negative bacteria toward hydrophobic
      compounds. Ultrasound treatment, cell age, and the phase state of phospholipid
      membranes were considered. Spin-labeling EPR method was used to quantify the
      penetration and distribution of a lipophilic spin probe, 16-doxylstearic acid (16
      DS), in Pseudomonas aeruginosa cell membranes. This bacterium was chosen because
      of its reported resistance to the action of hydrophobic antibiotics caused by the
      low permeability of the outer cell membrane for hydrophobic compounds. EPR
      spectra were collected from cell pellets and cell lysates. The overall spin probe
      uptake was measured in 10% SDS-cell lysates. Lysis with 0.6% SDS revealed the
      fraction of the probe located in membrane sites readily accessible to the
      surfactant. The results indicated a structural heterogeneity of P. aeruginosa
      membranes, with the presence of structurally "stronger" and "weaker" sites
      characterized by different susceptibility to the SDS treatment. The intracellular
      concentration of 16-DS was higher in insonated cells and increased linearly with
      the sonication power. EPR spectra indicated that ultrasound enhanced the
      penetration of the probe into the structurally stronger sites of the inner and
      outer cell membranes. The effect of ultrasound on the cell membranes was
      transient in that the initial membrane permeability was restored upon termination
      of the ultrasound treatment. These results suggest that the resistance of gram
      negative bacteria to the action of hydrophobic antibiotics was caused by a low
      permeability of the outer cell membranes. This resistance may be reduced by the
      simultaneous application of antibiotic and ultrasound. This hypothesis was
      confirmed in our experiments with P. aeruginosa exposed to erythromycin.

PMID- 9244389
TI  - Secondary structure of recombinant human cystathionine beta-synthase in aqueous
      solution: effect of ligand binding and proteolytic truncation.
AB  - The secondary structural composition and substrate-induced conformational changes
      of recombinant human cystathionine beta-synthase (CBS) in aqueous solution have
      been investigated in its full-length form (tetramer of 63-kDa subunits) by
      Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopies. In
      addition, structural comparison of a proteolytic truncated form (dimer of 45-kDa
      subunits) to that of the full-length enzyme has also been carried out. Second
      derivative and Fourier self-deconvolutional enhanced infrared spectra revealed
      amide I band components ascribed to beta-sheet (1689, 1638, and 1627 cm(-1)),
      alpha-helix (1658 cm(-1)), beta-turn (1679 and 1668 cm(-1)), and unordered (1651
      cm(-1)) structures in the spectra of the full-length enzyme. Quantitative
      analysis of FT-IR and CD spectra reveals that the full-length enzyme consists of
      about 48-53% beta-sheet, 25-30% alpha-helix, 8-10% turn, and 10-19% unordered
      structures. Under constraint of the spectroscopic data, theoretical prediction of
      locations of these secondary structural elements using Garnier's method shows
      that human CBS may contain a beta-sheet/alpha-helix/beta-sheet core structure.
      Second-derivative spectrum of the truncated enzyme exhibited all the major
      spectral features that are present in the full-length enzyme, indicating a
      preservation of the core structure of the enzyme. Significant differences were
      observed between the infrared spectra of the enzymes with or without the
      substrate, serine, indicating a substrate-induced conformational change in the
      enzyme, which did not result in a change in overall composition of secondary
      structural content based on quantitative analysis of FT-IR and far-UV CD spectra.

PMID- 9244390
TI  - Soybean Bowman-Birk protease inhibitor is a highly effective inhibitor of human
      mast cell chymase.
AB  - Soybean Bowman-Birk protease inhibitor (BBI) is an inhibitor of serine proteases
      with two functional inhibitory domains of different specificities: one is
      specific for chymotrypsin-like proteases, the other for trypsin-like proteases.
      Chymase and tryptase are serine proteases which are stored in mast cell granules
      and released upon degranulation. This work investigated the inhibition of human
      chymase and tryptase by BBI. Active-site titration of human skin chymase by BBI
      demonstrated that BBI was a highly effective inhibitor of human chymase.
      Virtually stoichiometric inhibition of chymase by BBI was observed at 10 nM
      chymase. Kinetic studies of the inhibition reaction yielded an association rate
      constant of 4.0 x 10(5) M(-1) s(-1) and a dissociation rate constant of 1.7 x 10(
      5) s(-1). From these two constants we estimate a K(i) of 50 pM. Chymase/BBI
      complexes did not dissociate in SDS-PAGE analyses under nonreducing conditions,
      consistent with the formation of a very tight complex with little tendency to
      dissociate. In contrast to chymase, human tryptase was not inhibited by BBI.
      These studies demonstrate that BBI is a good inhibitor of human chymase,
      exhibiting reaction properties better than physiological inhibitors described to
      date.

PMID- 9244391
TI  - Mutations in the IDH2 gene encoding the catalytic subunit of the yeast NAD+
      dependent isocitrate dehydrogenase can be suppressed by mutations in the CIT1
      gene encoding citrate synthase and other genes of oxidative metabolism.
AB  - During a screen for respiration competent yeast mutants that were unable to grow
      with acetate as a carbon source, two idh2 cit1 double mutants were identified.
      These strains were defective in the catalytic subunit of the NAD(+)-dependent
      isocitrate dehydrogenase and citrate synthase of the tricarboxylic acid (TCA)
      cycle. The strains harboring the idh2 alleles from these strains had two unusual
      phenotypes. First, their growth on many nonfermentable carbon sources was much
      poorer than strains containing other idh2 mutations. Second, the poor growth
      phenotype could be suppressed by the presence of mutations in CIT1 and other
      genes encoding oxidative functions. Spontaneous suppressor mutants that restore
      fast growth on glycerol medium to strains harboring two idh2 alleles were
      isolated, and a large percentage of the suppressor mutations have been identified
      within the CIT1 gene and at several other loci. Elevated levels of several TCA
      cycle proteins were observed in these idh2 mutants that were not observed in the
      presence of suppressing cit1 mutations. Citrate and isocitrate concentrations
      were also elevated in the idh2 mutants, but probably not to toxic levels. Five
      idh2 alleles were sequenced to understand the defects of the two classes of
      mutations. Sequence analysis indicated that the poor growth phenotype was caused
      by the loss of Idh2p protein. Similarly, eight cit1 alleles were sequenced to
      understand their characteristics as glycerol suppressors of idh2. These and other
      studies indicate that any mutation within CIT1 was capable of suppressing the
      idh2 mutations. Several models to explain these interactions are discussed.

PMID- 9244392
TI  - Comparison of prostaglandin H synthase isoform structures using limited
      proteolytic digestion.
AB  - Prostaglandin H synthase (PGHS) catalyzes a key step in the biosynthesis of a
      variety of bioactive lipid mediators. The two known isoforms (PGHS-1 and -2)
      share about 60% amino acid identity, but exhibit distinct interactions with
      substrates, activators, and inhibitors. Ovine PGHS-1 has previously been shown to
      have a distinctive protease-sensitive site near Arg277; cleavage by trypsin,
      chymotrypsin, or proteinase K produces fragments of 33 and 38 kDa and loss of
      activity. The ovine PGHS-1 crystal structure shows Arg277 located in an exposed
      loop structure; homology modeling predicts similar loop structures for both human
      isoforms (hPGHS-1 and -2). We have used limited proteolytic digestion of
      recombinant hPGHS-1 and hPGHS-2 to probe their structures. Incubation of hPGHS-1
      with either trypsin or proteinase K produced 33- and 38-kDa fragments and loss of
      activity. In contrast, incubation of hPGHS-2 with the same proteases led to
      cleavage of only a 2- to 3-kDa fragment, with no decrease in activity.
      Immunoblotting with site-specific antibodies demonstrated that the cleaved
      fragment originated from the hPGHS-2 C-terminus. Similar immunoblotting
      experiments indicated that trypsin did not attack the ovine PGHS-1 C-terminus.
      Mutagenesis was used to replace Pro263 of hPGHS-2 (corresponds to Arg277 of ovine
      PGHS-1) with arginine, inserting a potential trypsin site. Incubation of this
      P263R hPGHS-2 mutant with either trypsin or proteinase K resulted in cleavage
      near the C-terminus and retention of activity, just as with wild-type hPGHS-2. A
      peptide containing residues 259-268 of the P263R mutant was cleaved by trypsin at
      the same rate as a peptide corresponding to hPGHS-1 residues 272-281,
      demonstrating that the sequence differences were not responsible for the lack of
      tryptic cleavage at residue 263 in the hPGHS-2 mutant. Preincubation of hPGHS-2
      with graded levels of guanidinium HCl before incubation with proteinase K did not
      produce large proteolytic fragments, indicating that the hPGHS-2 loop region was
      not selectively unfolding. The results point to two regions of significant
      structural difference between PGHS-1 and -2: the Arg277 loop, which is protease
      sensitive in PGHS-1 but protease-resistant in PGHS-2, and the C-terminus, which
      is protease-sensitive in PGHS-2 but not in PGHS-1.

PMID- 9244393
TI  - Hydrodynamic properties of Vibrio harveyi acyl carrier protein and its fatty
      acylated derivatives.
AB  - The amino acid sequence of Vibrio harveyi acyl carrier protein (ACP) is 86%
      identical to that of Escherichia coli ACP, although five nonconservative amino
      acid differences are concentrated in the loop region between helices I and II
      (residues 18-25). We have investigated the influence of these sequence
      differences on the hydrodynamic properties of the two ACPs and their fatty
      acylated derivatives. Hydropathy analysis suggests that V. harveyi ACP is more
      hydrophobic than E. coli ACP in the loop region, a prediction supported by
      stronger binding of V. harveyi acyl-ACPs (C12 to C16) to octyl-Sepharose. Gel
      filtration experiments indicated that both ACPs undergo a similar conformational
      expansion when pH was elevated from 7.5 (R(s) = 24 A) to 9.0 (R(s) = 30 A). Fatty
      acylation reversed this expansion: R(s) for 16:0-ACP was 12 A, independent of ACP
      source and pH. By contrast, V. harveyi and E. coli ACPs exhibited distinct gel
      electrophoretic properties. Fatty acylation of V. harveyi ACP produced a greater
      increase in mobility on a conformationally sensitive native gel system. Moreover,
      while both V. harveyi and E. coli ACPs migrated anomalously at 20 kDa on SDS
      polyacrylamide gel electrophoresis, they exhibited strikingly different behavior
      on SDS gels upon acylation with longer chain fatty acids. These results indicate
      that E. coli and V. harveyi ACPs exhibit similar overall pH- and fatty acid
      dependent conformational changes, but gel electrophoresis is more sensitive to
      structural differences due to variations of hydrophobicity and charge.

PMID- 9244394
TI  - Parallel detection of Na,K-ATPase alpha subunit isoforms by pan-specific
      monoclonal mAb 9A7.
AB  - While emphasis has been placed upon those proteins which either mediate or
      respond to the rapid influx of calcium following depolarization, there has been
      little emphasis upon those proteins which aid in the reequilibration of the
      membrane potential. In an effort to identify presynaptic membrane proteins
      implicated in neurosecretion, monoclonal antibodies were screened against
      proteins which cosegregated with neuronal voltage-dependent calcium channels
      (VDCC) following immunoprecipitation. One monoclonal antibody (mAb 9A7)
      identified a 110-kDa protein. Micropeptide sequencing of (i) the mAb 9A7
      immunoaffinity purified antigen and (ii) the 110-kDa protein present in the
      neuronal (N-type) VDCC preparation (McEnery et al., 1991, Proc. Natl. Acad. Sci.
      88, 11095-11099) indicated identity with the alpha subunit(s) of the Na,K-ATPase.
      Further characterization by Western blotting, immunochemical localization, and
      immunoaffinity purification indicated that mAb 9A7 not only recognized the alpha3
      isoform which is predominant in neuronal tissues but also identified the alpha1
      and alpha2 isoforms. mAb 9A7 exhibited a wide cross-species reactivity and
      recognized human, rat, and mouse alpha subunit isoforms at an internal epitope.
      The pan-specificity of mAb 9A7 and the differential mobility of the alpha1
      isoform relative to the alpha2 and alpha3 permitted parallel detection of
      multiple alpha isoforms. Western blot analysis of undifferentiated rat
      pheochromocytoma cell line (PC12) and human neuroblastoma (IMR32) cells indicated
      coexpression of the alpha1 and alpha3 isozymes. Upon differentiation of IMR32
      cells by dibutrylyl-cAMP, a substantial increase in the alpha3 relative to the
      alpha1 isoform was observed. While the enrichment of total Na,K-ATPase may
      reflect the increased demand for ATP-dependent ion transport as IMR32 cells
      become more excitable, the specific increase in the alpha3 isoform suggests a
      unique role of this isoform during IMR32 cell differentiation.

PMID- 9244395
TI  - Purification and kinetic characterization of Haemophilus parasuis malate
      dehydrogenase.
AB  - Haemophilus parasuis malate dehydrogenase ((S)-malate:NAD+ oxidoreductase; EC
      1.1.1.37) isolated from cell sonicates was purified 584-fold to electrophoretic
      homogeneity with a 19% recovery and a specific activity of 222 units/mg protein.
      SDS-polyacrylamide gel electrophoresis and molecular exclusion chromatography
      indicated the purified enzyme to be a dimer composed of 34,600 molecular weight
      subunits. Kinetic parameters for all four substrates in the forward and reverse
      reactions indicated a sequential mechanism for this enzymic process. Product and
      dead-end inhibition studies were consistent with an ordered bi-bi mechanism in
      which NAD is the first substrate bound to the enzyme and NADH the second product
      released. Protection against thermodenaturation of the enzyme by NAD and not by
      malate was supportive of this mechanism. A pronounced product inhibition by NADH
      (K(i) = 9.0 microM) was observed. Although NADP did not serve as a coenzyme, a
      number of analogs of NAD structurally altered in the nitrogen base moieties were
      observed to function as coenzymes in the oxidation of malate catalyzed by the
      purified malate dehydrogenase. Coenzyme-competitive inhibition of the malate
      dehydrogenase was observed with five adenosine derivatives and six structural
      analogs of NAD. Of the NAD analogs studied as inhibitors, 3-pyridylcarbinol
      adenine dinucleotide was the most effective (K(i) = 18 microM). Although
      inhibition of growth of H. parasuis by this analog was observed, it was less
      effective (K(i) = 136 microM) than the inhibition of the purified dehydrogenase.

PMID- 9244396
TI  - Mode of interactions of human aldolase isozymes with cytoskeletons.
AB  - Three isoforms of fructose-1,6-bisphosphate aldolase were found to bind
      specifically to the actin-containing filament of the cytoskeleton and to show
      tissue-specific binding patterns. Aldolase A (muscle type) bound more tightly to
      the skeletal muscle cytoskeleton among the three isozymes, while aldolase B
      (liver type) preferred the liver cytoskeleton to those of other tissues. The
      specific binding of aldolase A to the skeletal muscle cytoskeleton was inhibited
      strongly by the substrates fructose 1,6-bisphosphate and fructose 1-phosphate.
      Several mutant aldolases A were examined to identify the amino acid residues or
      regions that play a role in specific binding. Among the mutant aldolases tested,
      A-E34D, A-K41N, and A-Y363S exhibited remarkably reduced binding activities.
      Experiments using FITC-labeled enzymes and Rh-labeled phalloidin disclosed that
      aldolase A associated with the cytoskeleton. Specifically, when aldolase A was
      incubated with human fibroblast MRC-5 permeabilized with Triton X-100, aldolase A
      bound to the actin filaments in the stress fibers within the cell. Aldolase A
      reversibly inhibited the contraction of MRC-5 cells which usually occurred in the
      presence of Mg2(+)-ATP and Ca2+. These results provide direct evidence that
      aldolase binds specifically to the actin-containing stress fibers and suggest
      that aldolase may regulate cell contraction through its reversible binding to the
      filaments in the permeabilized MRC-5 fibroblast.

PMID- 9244397
TI  - Myoglobin-catalyzed bis-allylic hydroxylation and epoxidation of linoleic acid.
AB  - Linoleic acid was treated with metmyoglobin and cumene hydroperoxide at 0 degrees
      C under anaerobic conditions. Five major compounds were identified, i.e., 11
      hydroxylinoleic acid (29% yield), cis-9,10-epoxy-(12Z)-octadecenoic acid (16%),
      cis-12,13-epoxy-(9Z)-octadecenoic acid (8%), 9-hydroxy-(10E,12Z)-octadecadienoic
      acid (4%), and 13-hydroxy-(9Z,11E)-octadecadienoic acid (4%). Steric analysis
      showed that these compounds were all racemic. The steric course of the formation
      of the major metabolite, (11R,S)-hydroxylinoleic acid, was studied by incubation
      of linoleic acids stereospecifically deuterated at C-11. It was found that the
      (11R)-hydroxylinoleic acid lost most of the deuterium label when formed from
      [(11R)-2H]linoleic acid but retained the label when formed from [(11S)
      2H]linoleic acid. Furthermore, the (11S)-hydroxylinoleic acid retained and lost
      most of the label when produced from [(11R)-2H]- and [(11S)-2H]linoleic acids,
      respectively. Thus, although the myoglobin-promoted hydroxylation of linoleic
      acid into 11-hydroxylinoleic acid lacked apparent stereospecificity and produced
      equal amounts of the R and S enantiomers, the course of the reaction was
      stereospecific and involved hydrogen abstraction and oxygen insertion occurring
      with retention of absolute configuration of the carbon atom hydroxylated.

PMID- 9244398
TI  - Cisplatin inhibits protein synthesis in rabbit reticulocyte lysate by causing an
      arrest in elongation.
AB  - The mechanism through which cisplatin (cis-diamminedichloroplatinum) inhibits
      protein synthesis in rabbit reticulocyte lysate was characterized. Cisplatin and
      transplatin caused a progressive slowing in the rate of protein synthesis
      culminating in the complete arrest of translation. Inhibition was dependent upon
      the aquation of the compounds. Addition of eukaryotic initiation factor eIF-2,
      eIF-2B, cAMP, MgGTP, or dithiothreitol neither prevented nor reversed the
      inhibition induced by cisplatin, indicating that the mechanism of cisplatin
      induced translational inhibition is distinct from the inhibition induced by other
      toxic heavy metal ions (Hurst, R., Schatz, J. R., and Matts, R. L. (1987) J.
      Biol. Chem. 262, 15939-15945; Matts, R. L., Schatz, J. R., Hurst, R., and Kagen,
      R. (1991) J. Biol. Chem. 266, 12695-12702). Analysis of the polyribosome profile
      of cisplatin-inhibited reticulocyte lysate indicated that cisplatin arrests the
      elongation stage of protein synthesis. Agarose gel electrophoresis and Northern
      blot analysis indicated that mRNA and rRNA become crosslinked to form very high
      molecular-weight adducts upon extraction of the RNA from polyribosomes of
      cisplatin-treated lysates. Diethyldithiocarbamate, which reduces the cytotoxicity
      of cisplatin in vivo, protects protein synthesis in reticulocyte lysate from
      inhibition by cisplatin. The data suggest that extensive derivatization of
      reticulocyte lysate RNA by cis- and transplatin results in the arrest of
      translating ribosomes. Since arrest of translational elongation is a well-defined
      mechanism of action of several families of toxins, we suggest that it may
      contribute to the cytotoxic action of cisplatin observed in certain populations
      of cells.

PMID- 9244399
TI  - Entomopathogenous fungi degrade epicuticular hydrocarbons of Triatoma infestans.
AB  - Studies were undertaken to analyze the ability of entomopathogenous fungi to
      degrade insect hydrocarbons. Strains of Beauveria bassiana and Metarhizium
      anisopliae pathogenic to the blood-sucking bug Triatoma infestans were grown on
      hydrocarbon and non-hydrocarbon insect lipid extracts and on synthetic
      hydrocarbon-enriched media as the sole carbon source. Entomopathogenous fungi
      were shown to utilize hydrocarbons as the only carbon source for their growth.
      Insect-derived hydrocarbons served more efficiently as metabolic fuel rather than
      synthetic compounds of similar structure. [3H]n-Pentacosane, [11,12-3H]3,11
      dimethylnonacosane, and [14C]n-hexadecane were catabolized into different amounts
      of polar lipids, free fatty acids, and acylglycerols. In experiments using the
      branched alkane, labeled hydrocarbons of different chain length than the
      precursor were also synthesized. Evidence of complete catabolism was obtained by
      a significant release of 14CO2 from [1-14C]n-hexadecane. 14CO2 production might
      be used as a simple method to compare hydrocarbon utilization by fungal strains.
      These data demonstrate that entomopathogenous fungi are able to transform a
      variety of hydrocarbon structures into different lipid products, part of which
      may be subsequently utilized for energy production and for the biosynthesis of
      cellular components. These data are the first evidence of hydrocarbon catabolism
      and synthesis in entomopathogenous fungi.

PMID- 9244400
TI  - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase unmask
      transcriptional regulation of hepatic low-density lipoprotein receptor gene
      expression by dietary cholesterol.
AB  - The mechanism by which dietary cholesterol regulates expression of the hepatic
      low-density lipoprotein (LDL) receptor was investigated. In a previous study
      (Arch. Biochem. Biophys. 325, 242-248, 1996), we demonstrated that dietary
      cholesterol reduces the rate of LDL receptor protein degradation without
      affecting steady-state levels of receptor protein. In view of these findings, it
      was expected that dietary cholesterol would decrease the rate of transcription of
      the hepatic LDL receptor gene, resulting in lower mRNA levels and lower rates of
      synthesis of LDL receptor protein. Surprisingly, neither the rate of
      transcription nor the level of LDL receptor mRNA was reduced in response to
      dietary cholesterol, even though hepatic cholesterol levels were increased
      twofold. This suggests that under normal conditions, dietary cholesterol does not
      affect LDL receptor gene expression at the level of transcription. In contrast,
      feeding 2% cholesterol to rats fed a diet supplemented with 0.04% lovastatin
      significantly decreased hepatic LDL receptor mRNA levels and transcription rates.
      These results suggest that lovastatin unmasks transcriptional regulation of the
      hepatic LDL receptor by dietary cholesterol. The levels of the mature nuclear
      forms of sterol response element binding proteins-1 and -2 were unaffected
      despite significant changes in hepatic cholesterol levels, mRNA levels, and
      transcription rates caused by lovastatin treatment. This suggests that the
      observed changes in transcription rates may not be mediated by these proteins in
      rat liver.

PMID- 9244401
TI  - Regulation of hepatic lecithin:retinol acyltransferase activity by retinoic acid
      receptor-selective retinoids.
AB  - The microsomal enzyme LRAT esterifies retinol and has been implicated in the
      hepatic storage of vitamin A. Previously, we showed that hepatic LRAT activity is
      negligible during vitamin A deficiency and that all-trans-retinoic acid (all
      trans-RA) rapidly induces the activity of liver LRAT in retinoid-deficient rats.
      In the present studies, we have examined the ability of natural and synthetic
      retinoids to induce liver LRAT activity in retinoid-deficient rats. The natural
      retinoids retinol, all-trans-RA (100 microg), 9-cis-RA, or equal molar amounts of
      other retinoids were injected ip and LRAT specific activity was measured in liver
      homogenates 17-18 h later. In retinoid-deficient rats, liver LRAT activity was
      extremely low [0.13 +/- 0.03 pmol retinyl ester (RE)/min/mg liver protein, mean
      +/- SE]. The natural retinoids retinol and all-trans-RA strongly induced LRAT
      activity (12.71 +/- 1.09 and 13.10 +/- 1.55 pmol RE/min/mg, respectively),
      whereas 9-cis-RA induced a lower level of LRAT activity (3.96 +/- 1.88 pmol
      RE/min/mg, P < 0.001 vs all-trans-RA). The retinoic acid receptor (RAR)-selective
      analog (RAR pan-agonist) all-trans-UAB8 and the RAR-alpha-selective retinoid
      Am580 also strongly induced LRAT activity. In contrast, neither RXR-selective
      agonists nor retinoids having a retro structure were active. For retinoids with
      significant RAR-alpha binding activity there was a strong direct correlation
      between receptor binding in vitro and the ability to induce hepatic LRAT activity
      in vivo (r2 = 0.920). These data implicate the RARs in the induction of hepatic
      LRAT and suggest a predominant role for RAR-alpha-active ligands.

PMID- 9244402
TI  - A novel mammalian high-molecular-weight aminopeptidase.
AB  - Studies with the human lymphoma U937 cell line revealed the presence of two
      soluble aminopeptidase activities. Using specific antisera one of these was
      identified as the puromycin-specific aminopeptidase, while the other appeared to
      be a novel approximately 200-kDa activity. The kinetic properties of this high
      molecular-weight aminopeptidase, referred to as Ap200, were similar to those of
      the puromycin-sensitive aminopeptidase, but showed quantitative differences.
      Ap200 is relatively insensitive to inhibition by both puromycin, K(i) = 27
      microM, and bestatin, K(i) = 1.6 microM. Among the synthetic beta-naphthylamides,
      Ap200 is more specific for alanine-beta-naphthylamide compared to the puromycin
      sensitive aminopeptidase. Similarly, this enzyme cleaves a more limited number of
      physiological peptides exhibiting a preference for the enkephalins. Ammonium
      sulfate, but not sodium chloride at the same ionic strength, was able to
      dissociate the high-molecular-weight aminopeptidase to a approximately 100-kDa
      active form. The high-molecular-weight aminopeptidase is found as a low abundant
      protein in a number of tissues including intestine, kidney, liver, lung, muscle,
      spleen, and testes, but could not be detected in adrenal, heart, or brain. Thus,
      it has a tissue distribution which differs from the puromycin-sensitive
      aminopeptidase.

PMID- 9244403
TI  - Steady-state kinetics of reduction of coenzyme Q analogs by glycerol-3-phosphate
      dehydrogenase in brown adipose tissue mitochondria.
AB  - We have undertaken a study of the role of coenzyme Q (CoQ) in glycerol-3
      phosphate oxidation in mitochondrial membranes from hamster brown adipose tissue,
      using either quinone homologs, as CoQ1 and CoQ2, or the analogs duroquinone and
      decylubiquinone as artificial electron acceptors. We have found that the most
      suitable electron acceptor for glycerol-3-phosphate:CoQ reductase activity in
      situ in the mitochondrial membrane is the homolog CoQ1 yielding the highest rate
      of enzyme activity (225 +/- 41 nmol x min(-1) x mg(-1) protein). With all
      acceptors tested the quinone reduction rates were completely insensitive to
      Complex III inhibitors, indicating that all acceptors were easily accessible to
      the quinone-binding site of the dehydrogenase preferentially with respect to the
      endogenous CoQ pool, in such a way that Complex III was kept in the oxidized
      state. We have also experimentally investigated the saturation kinetics of
      endogenous CoQ (1.35 nmol/mg protein of a mixture of 70% CoQ9 and 30% CoQ10) by
      stepwise pentane extraction of brown adipose tissue mitochondria and found a K(m)
      of the integrated activity of glycerol-3-phosphate cytochrome c reductase for
      endogenous CoQ of 0.22 nmol/mg protein, indicating that glycerol-3-phosphate
      supported respiration is over 80% of V(max) with respect to the CoQ pool. A
      similar K(m) of 0.19 nmol CoQ/mg protein was found in glycerol-3-phosphate
      cytochrome c reductase in cockroach flight muscle mitochondria.

PMID- 9244404
TI  - IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature
      Committee of IUBMB (NC-IUBMB).

PMID- 9244405
TI  - The mode of ceramide action: the alkyl chain protrusion model.
AB  - Ceramides can induce cellular differentiation, activation, survival and apoptosis
      and thus appear capable of changing the life style of virtually any cell type.
      Ceramides have been shown to play important roles in a variety of signal
      transduction systems. Within the last few years much has been learnt about the
      biology of ceramide, yet we understand little about the molecular mode of
      ceramide action. To reconcile the plethora of published functional data with the
      biochemical properties of ceramide, a model is proposed in which the alkyl chain
      of ceramide interacts with a hydrophobic cavity of a signalling protein. This
      model implies that ceramide, through protrusion of an alkyl chain, provides a
      lipid anchor to recruit proteins to membranes. The topology and kinetics of
      ceramide production by sphingomyelinases may thus play a pivotal role in the
      inducible compartmentalization and activation of signal transduction complexes.

PMID- 9244406
TI  - Phospholipase C-gamma1: regulation of enzyme function and role in growth factor
      dependent signal transduction.
AB  - Phospholipase C(gamma)1 (PLC-gamma1), a tyrosine kinase substrate, is a multi
      domain molecule that modulates the intracellular levels of the second messenger
      molecules: Ca2+ and diacylglycerol. Although a wide variety of growth factor
      receptor tyrosine kinases phosphorylate and activate PLC-gamma1, the biological
      role and necessity of this signal transduction element in mitogenesis has
      remained unclear. Recent results, however, point to a more essential role than
      was suggested by initial studies. Also, biochemical studies have indicated a
      putative means for the intramolecular repression of PLC-gamma1 activity and
      provide a means for interpreting activation signals through a derepression
      mechanism.

PMID- 9244408
TI  - Control of invasive growth by hepatocyte growth factor (HGF) and related scatter
      factors.
AB  - Hepatocyte growth factor (HGF) is the prototype of a family of structurally
      related soluble molecules, named scatter factors (SFs). These control a complex
      genetic programme leading to cell-dissociation, migration in the extracellular
      matrix, growth, acquisition of polarity and tubule formation. This programme is
      pivotal during the embryonic development of epithelial and some mesodermal
      derived tissues. In the adult HGF sustains cell survival and regeneration. A
      structurally related molecule, originally identified as macrophage stimulating
      protein (MSP), triggers the same complex genetic programme in epithelial and
      neural cells. The receptors for HGF and MSP are the tyrosine kinases encoded by
      the homologous genes MET and RON. As a distinctive feature, these receptors act
      via a two-phosphotyrosine docking site, capable of concomitant activation of
      multiple intracellular transducers and signalling pathways. In a number of
      malignant tumours, MET and RON constitutively sustain the genetic programme of
      scattering, leading to invasive growth and metastatic phenotype. Four MET-related
      receptors have been recently identified (the SEX protein family). These molecules
      are predominantly expressed during development and are likely to mediate
      repelling cues between cells of different type.

PMID- 9244407
TI  - Immunostimulatory cytokines in somatic cells and gene therapy of cancer.
AB  - The use of immunostimulatory cytokines has become an increasingly promising
      approach in cancer immunotherapy. The major goal is the activation of tumour
      specific T lymphocytes capable of rejecting tumour cells from patients with low
      tumour burden or to protect patients from a recurrence of the disease. Strategies
      that provide high levels of immunostimulatory cytokines locally at the site of
      antigen have demonstrated pre-clinical and occasional clinical efficacy. Animal
      models using poorly immunogenic tumours revealed that tumour cells genetically
      engineered to produce cytokines like IL-2, IL-4, IL-7, IL-12, IFNs, GM-CSF or TNF
      alpha were found to be effective in eradicating disseminated tumours.
      Experimental data obtained from these different animal models are reviewed here
      to provide an overview of this rapidly evolving field. The data obtained so far
      from clinical trials involving cytokine gene-modified cells have provided
      important information regarding the feasibility, safety, immunological effects
      and occasional clinical responses.

PMID- 9244410
TI  - How much benefit can be expected from matching for minor antigens in allogeneic
      marrow transplantation?
AB  - The presence of recipient disparity for a minor histocompatibility antigen termed
      HA-1 is associated with an increased risk of grades II-IV GVHD after marrow
      transplantation from an HLA-identical sibling. These data offer an opportunity to
      test the validity of theoretical models suggesting that the minor antigens
      capable of eliciting GVHD in any given individual are encoded by approximately
      seven genetic loci. Published data and theoretical models agree that there is
      little benefit to be gained by typing and matching at a single locus. The models
      predict, however, that substantial benefit would be possible if multiple loci
      could be typed. The success of matching would be enhanced by the availability of
      assays that would allow typing for at least four of the loci encoding antigens
      that could cause GVHD in any given individual.

PMID- 9244409
TI  - TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity.
AB  - The pro-inflammatory cytokines IL-1 and TNF-alpha are primary mediators of the
      acute phase response, the complex reaction of the mammalian organism to infection
      and injury. Among the genes activated by TNF-alpha and IL-1 in a variety of cells
      is TNF-stimulated gene 6 (TSG-6). The TSG-6 cDNA encodes a secreted 35 kDa
      glycoprotein which is abundant in synovial fluids of patients with various forms
      of arthritis and detectable in serum of patients with different inflammatory or
      autoimmune disorders. TSG-6 protein consists of two structural domains: a
      hyaluronan-binding link module, the characteristic domain of the hyaladherin
      family of proteins, and a C-terminal CUB domain, present in a variety of diverse
      proteins. TSG-6 forms a stable complex with components of the plasma protein
      inter-alpha-inhibitor (I[alpha]I), a Kunitz-type serine protease inhibitor. TSG-6
      and I(alpha)I synergize to inhibit plasmin, a serine protease involved in the
      activation of matrix metalloproteinases which are part of the proteolytic cascade
      associated with inflammation. Recombinant human TSG-6 protein exerts a potent
      anti-inflammatory effect in a murine model of acute inflammation. Modulation of
      the proteolytic network associated with inflammatory processes may be a mechanism
      whereby TSG-6, in cooperation with I(alpha)I, inhibits inflammation. Activation
      of the TSG-6 gene by pro-inflammatory cytokines, presence of TSG-6 protein in
      inflammatory lesions and its anti-inflammatory effect suggest a role for TSG-6 in
      a negative feed-back control of the inflammatory response.

PMID- 9244411
TI  - German consensus on immunogenetic donor search for transplantation of allogeneic
      bone marrow and peripheral blood stem cells.
AB  - In Germany allotransplantation of bone marrow or peripheral blood stem cells is
      presently performed by 34 different teams operating more or less independently.
      Thus, strategies of immunogenetic donor search, use of the various tissue typing
      techniques and policy on acceptable HLA mismatches in related and unrelated
      settings may vary considerably from one transplant centre to another. This paper
      summarises the results of the first German consensus meeting on immunogenetic
      donor search for bone marrow/peripheral blood stem cell grafting. The main goal
      of the participating transplant physicians and immunogeneticists was to define
      national standards for the above issues.

PMID- 9244412
TI  - Risk of extramedullary relapse following allogeneic bone marrow transplantation
      for acute myelogenous leukemia with leukemia cutis.
AB  - Leukemia cutis (LC) is a rare feature of acute myeloblastic leukemia (AML).
      Little information is available regarding its prognostic influence on post
      transplant outcome. In our institution, 202 patients with AML received an
      allogeneic HLA-identical marrow transplant from related donors between March 1982
      and January 1994. Thirteen patients had prior leukemic involvement of the skin
      (leukemia cutis or LC group) while 189 patients did not (non-LC group). There was
      a higher incidence of patients with the M4-M5 FAB subtypes in the LC group (83%)
      as compared to the non-LC group (33%). In addition, the percentage of patients
      transplanted in relapse was also higher in the LC group (69 vs 15%). While there
      were no differences observed in the rates of relapse post-transplant in the LC
      and non-LC groups when matched for stage of disease at transplant, the sites of
      relapse differed markedly. Five of six relapses in the LC group involved
      extramedullary sites as compared to only six of 38 relapses in the non-LC group
      (P = 0.002), with a 6-year probability of extramedullary relapse of 38.5% in the
      LC group as compared to 3.9% in the non-LC group. This increased probability of
      extramedullary relapse was independent of the FAB morphology (50 vs 2% for
      patients with the M4-M5 subtypes in the LC and the non-LC group respectively) and
      of disease status at the time of transplant. Moreover, only three relapses post
      transplant involved the skin, all of which were in the LC group, with a
      probability of skin relapse of 23.1% in this group. Patients with AML and
      leukemia cutis have a remarkable propensity to relapse in extramedullary sites
      following marrow transplantation. These relapses occur in the skin as well as
      other organs. Further investigations are needed to understand the biological
      basis of this clinical feature.

PMID- 9244413
TI  - High-dose chemotherapy with carboplatin, cyclophosphamide and etoposide and
      autologous transplantation for multiple myeloma relapsing after a previous
      transplant.
AB  - Eighteen extensively pre-treated patients (35-73 years, median 46) with relapsed
      multiple myeloma received salvage chemotherapy with 6 g/m2 cyclophosphamide, 800
      mg/m2 carboplatin, and 1800 mg/m2 etoposide (CCV) as a 96-h continuous infusion
      followed by autologous peripheral blood stem cells. The median number of prior
      chemotherapy regimens was five (range 4-10), including at least one autograft.
      Four patients died of toxicity, and one developed dialysis-dependent renal
      failure, while the others tolerated CCV well. Three of six patients with pre
      transplant creatinine of > 1 mg/dl died of toxicity compared with one of 12 with
      creatinine < or = 1 mg/dl (P = 0.083, Fisher's exact test). Three of four
      patients treated with four previous regimens showed > 50% reduction in tumor
      compared with one of 14 treated with > 4 regimens (P = 0.02, Fisher's exact
      test). At the last follow-up, five patients were alive at 8-24 months (median 13)
      with stable (n = 1) or progressive (n = 4) disease, and nine had died of
      progressive disease at 2.5-15 months (median 7). We conclude that CCV
      chemotherapy with autografting is tolerated well by extensively pre-treated
      myeloma patients provided the pre-transplant creatinine is normal, but toxicity
      in patients with abnormal renal function is high. The efficacy in multiply
      relapsed disease is poor, with response in only 22% of patients. CCV may deserve
      further evaluation early in the course of myeloma in patients with normal renal
      function.

PMID- 9244415
TI  - Increased serum levels of circulating intercellular adhesion molecule 1 predict
      the risk of graft rejection after bone marrow transplantation for thalassemia.
AB  - Beta thalassemia is a hereditary anemia curable by bone marrow transplantation
      (BMT). Class 3 patients have a much worse outcome with a high incidence of
      rejection after BMT. Adhesion molecules, including the intercellular adhesion
      molecule 1 are thought to play an essential role in the rejection process. To
      investigate whether increased levels of soluble intercellular adhesion molecule 1
      (sICAM-1) may be predictive of graft rejection, the pretransplant serum
      concentration of sICAM-1 of 27 beta thalassemic patients who rejected the graft
      was compared to that of 68 beta thalassemic patients who achieved a sustained
      engraftment. Fifty serum samples, obtained from marrow donors, matched for age
      and sex, served as controls. Beta thalassemic patients had significantly higher
      sICAM-1 concentrations as compared to controls (P = 0.0001). Significantly
      increased levels of sICAM-1 were found in the patients who subsequently rejected
      the graft (mean (95% CI) = 490 ng/ml (440; 540)) as compared to those with
      sustained engraftment (400 ng/ml (384; 415)), (P = 0.004). The mean level of
      sICAM-1 in patients with early rejection was significantly higher than that in
      patients with late rejection (P = 0.04). This may indicate a transfusion-mediated
      role of sICAM-1: some beta thalassemic patients with high sICAM-1 levels, induced
      by the transfusion support, may remain immunologically active, despite the
      conditioning regimen, therefore such patients are likely to have an early graft
      rejection. Our findings indicate that sICAM-1 could be a useful indicator of
      immune activation in polytransfused patients with beta thalassemia who have a
      high risk of rejection. Determination of sICAM-1 has potential clinical
      implications in predicting which patients may reject after BMT.

PMID- 9244414
TI  - Restoration of T and NK cell function in GM-CSF mobilized stem cell products from
      breast cancer patients by monocyte depletion.
AB  - Rapid immune reconstitution is observed following autologous peripheral blood
      stem cell transplantation (PSCT) as compared to autologous bone marrow
      transplantation (ABMT), although it is depressed compared to that observed in
      normal individuals. The immune dysfunction occurs despite the restoration of
      normal lymphoid cell numbers and may be associated with the immunologic
      characteristics of the infused peripheral blood stem cell (PSC) product. We
      report herein that the in vitro T cell proliferation and NK activity in PSC
      products of breast cancer patients are significantly increased following the
      removal of CD14+ monocytes (33 +/- 2% of the PSC product) by carbonyl iron
      magnetic cell isolation (CI). In vitro expansion of PSC cells cultured for 7-21
      days in the presence of interleukin-2 (IL-2) is also significantly increased by
      depletion of the phagocytic cells. The PHA and IL-2 mitogenic responses, as well
      as NK activity of the expanded cells, was also significantly increased by the
      depletion of the phagocytes. In summary, the depletion of phagocytic monocytes
      from PSC products restores the proliferative and functional properties of T and
      NK lymphocytes and may facilitate adoptive cellular therapy, as well as rapid
      immunologic reconstitution post-PSCT.

PMID- 9244417
TI  - Glucocorticoids fail to enhance the effect of FK506 and methotrexate in
      prevention of graft-versus-host disease after DLA-nonidentical, unrelated marrow
      transplantation.
AB  - Several steroid receptor-associated heat shock proteins can bind to FK506 as
      immunophilins. This has led to speculation that the steroid receptor and
      immunophilin signal transduction pathways are functionally interrelated. Indeed,
      in vitro work showed that FK506 treatment of intact L929 cells which were stably
      transfected with various reporter plasmids resulted in a potentiation of
      glucocorticoid hormone-induced glucocorticoid receptor-mediated gene
      transcription. These findings have raised the possibility of additive or
      synergistic immunosuppressive effects of FK506 and glucocorticoids. We tested
      this hypothesis in a canine model of GVHD prevention. Two groups of dogs were
      given 9.2 Gy total body irradiation followed by hematopoietic grafts from
      unrelated DLA-nonidentical donors. Among the first group of four recipients which
      were given FK506 and glucocorticoids, one rejected the graft, while three
      developed acute GVHD and died from associated complications between days 14 and
      34. In the second group of nine recipients which were given FK506,
      glucocorticoids and methotrexate (MTX), only one dog became a long-term survivor
      while eight dogs died between days 21-114 with GVHD (n = 5) or FK506-associated
      toxicities (n = 3). Thus, addition of glucocorticoids to FK506 or FK506/MTX
      showed neither synergistic nor additive effects with respect to GVHD prevention
      in this model, and no survival advantages were seen compared to previously
      reported results with FK506 alone or FK506 and MTX in combination, respectively.

PMID- 9244416
TI  - Induction of graft-versus-host disease as immunotherapy of leukemia relapsing
      after allogeneic transplantation: single-center experience of 32 adult patients.
AB  - Thirty-two adults (median age 36 years) with leukemia (15 AML, eight CML, six
      ALL, three CLL) persisting or relapsing 1-40 months (median 4) after allogeneic
      BMT (20 matched siblings, eight unrelated, four family mismatch) underwent
      immunotherapy to elicit GVHD. This comprised one or more of: infusion of donor
      cells (n = 22), stopping cyclosporine (n = 14), and administration of interferon
      alpha2b (n = 15) or interleukin-2 (n = 4). Eight acute leukemia patients received
      chemotherapy as well. The time from relapse to immunotherapy was 0-1344 days
      (median 4). Acute and/or chronic GVHD developed in 17 patients. Response was not
      evaluable in three patients due to early toxic death. There was no response in 10
      patients, whereas 19 showed objective response. Nine patients died due to
      toxicity and 10 due to progressive disease. Thirteen patients are alive 4-58
      months (median 14) after immunotherapy; 12 in remission (five AML, four chronic
      phase CML, one ALL, one accelerated phase CML, one CLL) and one with progressive
      disease (accelerated phase CML). Eleven of 13 patients who are alive had GVHD
      compared with six of 19 who died (P = 0.005, Fisher's exact test). We conclude
      that with the exception of CML in myeloid blast crisis, immunotherapy is active
      in most types of acute and chronic leukemia relapsing after allogeneic BMT. It is
      associated with considerable toxicity. Clinically obvious GVHD, especially
      chronic GVHD, results in a higher probability of survival.

PMID- 9244418
TI  - Comparison of cytomegalovirus (CMV) antigenemia and CMV in bronchoalveolar lavage
      fluid for diagnosis of CMV pulmonary infection after bone marrow transplantation.
AB  - A comparative cytomegalovirus (CMV) diagnostic study was carried out on 30 bone
      marrow transplant patients. Forty-three bronchoalveolar lavage fluid (BALF)
      samples from these patients were examined for CMV by viral culture, polymerase
      chain reaction (PCR), shell vial and cytology. In parallel, peripheral blood
      samples were subjected to CMV antigenemia assay. CMV was detected in 12 (27.9%)
      of the 43 BALF samples (10 samples in viral culture, 10 samples in PCR, eight
      samples in shell vial and three samples in cytology). The CMV antigenemia assay
      yielded a positive result for six samples. The rates of agreement between results
      of the CMV antigenemia assay and results of each of the BALF tests were as
      follows: 81.4% with viral culture, 76.7% with PCR, 86.0% with shell vial, and
      88.4% with cytology. Although the sensitivity of the CMV antigenemia assay was
      inferior to the sensitive tests of BALF samples, statistically significant
      correlations were demonstrated between the CMV antigenemia assay, viral culture,
      shell vial and cytology. Although the CMV antigenemia assay was shown to be
      useful for detection of CMV, it may be necessary to confirm not only the
      sensitivity but also the specificity of this method for prevention of CMV disease
      after BMT.

PMID- 9244419
TI  - A single [3H]thymidine-based limiting dilution analysis to determine HTLp and
      CTLp frequencies for bone marrow donor selection.
AB  - Histocompatibility between recipient and donor is a critical factor in allogeneic
      BMT which, to a large extent, determines the incidence of GVHD after BMT.
      Functional histocompatibility assays, such as the helper T lymphocyte precursor
      frequency assay (HTLp) and the cytotoxic T lymphocyte precursor frequency assay
      (CTLp), have proved to be helpful tools in facilitating donor selection
      procedures. However, a major drawback of these assays is that they are laborious
      and require large numbers of cells. We therefore adapted a [3H]thymidine-based
      assay, the 'JAM' test, as a read-out for CTLp frequencies, to replace the more
      cumbersome 51Cr-release assay. Furthermore, we applied an experimental setup that
      enables the assessment of HTLp and CTLp frequencies from a single limiting
      dilution assay to reduce the number of cells needed. The newly developed assay is
      relatively easy to perform and has the advantage that different subsets of T
      cells can be quantified in a single ongoing alloreaction. When the combined assay
      was applied in unrelated donor selection it proved to be a sensitive method that
      enables differentiation in suitability of distinct donors for a single patient.
      Therefore, the combined HTLp/CTLp assay appears to be a practical and sensitive
      method for identifying functional histocompatibility in related and unrelated
      donor/recipient combinations.

PMID- 9244421
TI  - BK papova virus pneumonia following hematopoietic stem cell transplantation.
AB  - BK papova virus infection is frequently seen after bone marrow transplantation as
      a causative agent of hemorrhagic cystitis. We report an 8-month-old child with
      osteopetrosis who died of a severe interstitial pneumonia after receiving an
      unrelated umbilical cord transplant. On autopsy, BK virus was detected in the
      lung tissue using immunofluorescence assay, cell culture and PCR. No other
      pathogens were recovered. BK virus infection should be considered as a cause of
      interstitial pneumonia in children undergoing transplantation.

PMID- 9244420
TI  - Evaluation of clinical scale CD34+ cell purification: experience of 71
      immunoaffinity column procedures.
AB  - Seventy-one mobilised PBSC collections were subject to CD34+ cell purification
      using the CEPRATE SC stem cell concentration system. The overall median purity of
      CD34+ cells was 69% (6-93%). CD34+ cell, and GM-CFC recoveries were 52% (8-107%)
      and 36% (3-118%). Purity was logarithmically related to the input percentage of
      CD34+ cells and starting requirements were established of 1% CD34 cell content
      for optimal purity and a minimum of 2 x 10(6)/kg CD34+ cells to ensure recovery
      of our minimum engraftment threshold of 1 x 10(6)/kg CD34+ cells. Reduction of
      the washing steps reduced non-specific cell losses and shortened the procedure
      but did not affect progenitor cell recovery. Purified CD34+ cells were reinfused
      following high-dose therapy in 35 patients. The median time to neutrophil
      recovery of 0.5 x 10(9)/l was 12 (10-23) days and to the attainment of platelet
      independence was 13 (7-100) days. The risks of delayed platelet recovery were
      related to the CD34+ cell dose infused and were identical to the risks when non
      purified PBSC collections were used. In conclusion, purification of CD34+ cells
      using the CEPRATE device is reliable and the purified product results in prompt
      engraftment. The cell losses that occur do however restrict its use in many
      patients.

PMID- 9244422
TI  - Role of tumor cells contaminating the graft in breast cancer recurrence after
      high-dose chemotherapy.
AB  - One of the possible drawbacks to autologous stem cell transplantation in breast
      cancer (BC) patients is the potential for tumor contamination in the transplanted
      product. We present a patient with advanced disease who received high-dose
      chemotherapy (HDC) and PBPC support as consolidation therapy after achieving
      complete remission with standard-dose first-line treatment, and suffered
      recurrence of the disease 6 months after transplantation. Retrospective analysis
      revealed the presence of contaminating cells in the leukapheretic product, and
      clinical evidence suggested a role for these cells in the tumor relapse.

PMID- 9244423
TI  - Effective high-dose chemotherapy followed by autologous peripheral blood stem
      cell transplantation in a patient with the aggressive form of cytophagic
      histiocytic panniculitis.
AB  - A 20-year-old Japanese man developed generalized, subcutaneous, painless nodules,
      fever, abnormal liver function, serosal effusions, hepatosplenomegaly,
      lymphadenopathy and anemia. Skin biopsies revealed lobular panniculitis with a
      morphologically benign histiocytic infiltration and prominent phagocytosis.
      Atypical T lymphocytes were also present in the skin and liver. The diagnosis
      given was aggressive cytophagic histiocytic panniculitis (CHP) or aggressive
      subcutaneous panniculitic T cell lymphoma (SPTCL). He received cyclophosphamide,
      doxorubicin, and vincristine on day 1, prednisolone on days 1-5, and etoposide on
      days 1, 3 and 5 (CHOP-E), with the support of granulocyte colony-stimulating
      factor. This regimen was repeated every 2 weeks and complete clinical remission
      (CCR) was attained after three cycles of CHOP-E. As the clinical course of
      aggressive CHP is recurrent and often fatal, he was given high-dose chemotherapy
      followed by autologous peripheral blood stem cell transplantation (APBSCT), after
      five cycles of CHOP-E. He has remained in CCR for 12 months after APBSCT. High
      dose chemotherapy followed by APBSCT is considered to be one of the most
      beneficial therapies for patients with aggressive CHP and aggressive phase SPTCL.

PMID- 9244424
TI  - Induction of graft-versus-leukemia effect in a patient with chronic lymphocytic
      leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is incurable with conventional therapy. Recent
      data report favorable results with allogeneic transplant. We report a patient
      with CLL with persistent leukemia post-transplant who obtained remission after
      discontinuing immune suppression.

PMID- 9244425
TI  - Resolution of invasive central nervous system aspergillosis in a transplant
      recipient.
AB  - Central nervous system (CNS) aspergillosis carries a uniformly poor prognosis in
      bone marrow transplant recipients. Amphotericin B can be bound to lipid carriers
      leading to improvement of its therapeutic index. We describe the successful
      medical management of CNS aspergillosis in an allogeneic bone marrow transplant
      patient with administration of Amphotericin B Lipid Complex.

PMID- 9244426
TI  - Increased incidence of CMV infection after allogeneic bone marrow transplantation
      from unrelated donors but doubts about an increase in CMV-associated disease.

PMID- 9244428
TI  - Two distinct deletions in the IDS gene and the gene W: a novel type of mutation
      associated with the Hunter syndrome.
AB  - A novel mutation has been identified in a patient with the Hunter syndrome
      (mucopolysaccharidosis type II), in whom the disorder is associated with two
      distinct deletions separated by 30 kb. The deletions were characterized by
      Southern blot and PCR analyses, and the nucleotide sequences at both junctions
      were determined. The first deletion, corresponding to a loss of 3152 bp of DNA,
      included exons 5 and 6 of the iduronate-2-sulfatase (IDS) gene. The second
      deletion was 3603 bp long and included exons 3 and 4 of gene W, which is located
      in the DXS466 locus telomeric of the IDS gene. Both deletions are the result of
      nonhomologous (illegitimate) recombination events between short direct repeats at
      the deletion breakpoints. An interesting finding was the presence of the heptamer
      sequence 5'-TACTCTA-3' present at both deletion junctions, suggesting that this
      motif might be a hot spot for recombination. We propose that the double deletion
      is the result of homology-associated nonhomologous recombinations caused by the
      presence of large duplicated regions in Xq27.3-q28.

PMID- 9244427
TI  - The human homogentisate 1,2-dioxygenase (HGO) gene.
AB  - Alkaptonuria (AKU; McKusick No. 203500), a rare hereditary disorder of the
      phenylalanine catabolism, was the first disease to be interpreted as an inborn
      error of metabolism (A. E. Garrod, 1902, Lancet 2: 1616-1620). AKU patients are
      deficient for homogentisate 1,2-dioxygenase (HGO; EC 1.13.11.5). This enzymatic
      deficiency causes homogentisic aciduria, ochronosis, and arthritis. Recently we
      cloned the human HGO gene and showed that AKU patients carry two copies of a loss
      of-function HGO allele. Here we describe the complete nucleotide sequence of the
      human HGO gene and the identification of its promoter region. The human HGO gene
      spans 54,363 bp and codes for a 1715-nt-long transcript that is split into 14
      exons ranging from 35 to 360 bp. The HGO introns, 605 to 17,687 bp in length,
      contain representatives of the major classes of repetitive elements, including
      several simple sequence repeats (SSR). Two of these SSRs, a (CT)n repeat in
      intron 4 and a (CA)n repeat in intron 13, were found to be polymorphic in a
      Spanish population sample. The HGO transcription start site was determined by
      primer extension. We report that sequences from -1074 to +89 bp (relative to the
      HGO transcription start site) are sufficient to promote transcription of a CAT
      reporter gene in human liver cells and that this fragment contains putative
      binding sites for liver-enriched transcription factors that might be involved in
      the regulation of HGO expression in liver.

PMID- 9244429
TI  - Physical and transcription map in the region 14q24.3: identification of six novel
      transcripts.
AB  - The region of chromosome 14q24 has been of particular interest as it is known to
      contain one of the early-onset Alzheimer disease genes (AD3). Other genes of
      medical interest, such as arrhythmogenic right ventricular cardiomyopathy, have
      been mapped to this region by linkage analysis or chromosome rearrangements. We
      have focused on the region of a balanced translocation (2;14)(p25;q24). Members
      of a family with this translocation all have anterior polar cataracts, suggesting
      the presence of a gene involved in lens integrity at the vicinity of the
      breakpoint. The chromosome 14 breakpoint has been defined between the short
      tandem repeats D14S289 and D14S277, a region of overlap for yeast artificial
      chromosomes (YACs) 888b2 and 934d4. We have extended the study of the region to 2
      Mb on chromosome 14 and present a physical map of this region, including several
      sequence-tagged sites. New probes were generated using several end clones and
      inter-Alu PCR fragments from YACs. cDNA selection was used to identify
      transcribed sequences. Mapping and alignment of 17 nonoverlapping cDNAs completed
      by sequence and expression pattern analysis suggested that a minimum of eight
      putative transcription units is present in this region: six of these units
      correspond to five new genes and one member of a new gene family.

PMID- 9244430
TI  - Organization of the human beta-adducin gene (ADD2).
AB  - The intron-exon organization of the human beta-adducin gene (ADD2) has been
      determined from overlapping genomic clones. The gene spans over 100 kb on
      chromosome 2p13 and comprises 17 exons. Seven of the exons are identical in size
      to the corresponding exons of the alpha-adducin gene (4p16.3), suggesting gene
      duplication. A 275-bp fragment 5' to exon 1 demonstrates strong promoter activity
      in a transient transfection assay. Within 333 bp 5' of the first exon can be
      found several putative transcription factor-binding sites: three SP1 sites, one
      GATA site, three MZF1 sites, one p300 site, and one c-Ets site. Alternatively
      spliced exons in the 3' region are described and contain distinct coding regions,
      stop codons, and 3'UTR, corresponding to previously published beta-adducin cDNA
      sequences beta-1 and beta-2. The alternative splice sites for the smallest
      adducin isoform, beta-3, are alternative donor and acceptor sites within exons 7
      and 12. The most recently described isoform, beta-4, includes an alternative exon
      (exon 15) that results in a frame shift and early termination. Intron-exon splice
      sites are presented for all 17 exons and conform to the consensus sequences for
      mammalian splice sites. These results will be useful in further analysis of
      tissue-specific expression of adducin isoforms and in analysis of DNA from
      patients with diseases mapping to this region of chromosome 2.

PMID- 9244431
TI  - Determination of the genomic structure of the XNP/ATRX gene encoding a potential
      zinc finger helicase.
AB  - The XNP/ATR-X gene is involved in several X-linked mental retardation phenotypes:
      the ATR-X syndrome, the Juberg-Marsidi syndrome, and some severe mental
      retardation phenotypes without alpha-thalassemia. Using a vectorette strategy, we
      have identified and sequenced the intron/exon boundaries of this gene. The gene
      is composed of 35 exons. It encodes a potential protein of 2492 amino acids. A
      search of the databases identified three zinc finger motifs within the 5' end of
      the gene. Expression analysis in different tissues indicated that an alternative
      splicing event that involves exon 6 is occurring. One of these alternatively
      spliced transcripts is predominantly expressed in embryonic tissues. These data
      led us to search for mutations in the 5' region in ATRX patients without other
      mutations in the 3' region. In one patient a mutation was found in which part of
      exon 7 was removed from the XNP transcript, as a result of a mutation creating a
      novel splice site that is substituted for the natural splice site. This new
      splicing event removed one zinc finger motif. This is the first example of a
      mutation in XNP within the 5' coding region. It suggests that mutations will be
      predominantly found in the helicase region as well as in the zinc finger regions
      and leads us to propose a large screening of additional patients.

PMID- 9244432
TI  - The human gene ZFP161 on 18p11.21-pter encodes a putative c-myc repressor and is
      homologous to murine Zfp161 (Chr 17) and Zfp161-rs1 (X Chr)
AB  - A clone from a lambda gt11 cDNA expression library of HeLa cells was isolated,
      sequenced, and shown to encode a new human zinc finger protein. The cDNA of the
      gene termed ZFP161 has an open reading frame of 1347 bp. The predicted protein
      comprises 449 amino acid residues and contains five zinc finger motifs of the
      Kruppel type near the C-terminus and a BTB/POZ domain in the N-terminal region.
      The protein is 98% homologous to a murine zinc finger protein, ZF5 (M. Numoto et
      al., 1993, Nucleic Acids Res. 21: 3767-3775), which is a putative transcriptional
      repressor of c-myc and exhibits growth-suppressive activity in mouse cell lines.
      Through the use of a panel of somatic cell hybrids for chromosomal assignment and
      DNAs of somatic cell hybrids containing a deleted chromosome 18 for fine mapping,
      the human gene ZFP161 was localized to 18p11.21-pter. Therefore, ZFP161 is a
      candidate gene by position for the holoprosencephaly type 4 gene, HPE4, which is
      involved in congenital malformations. With DNAs from an interspecific backcross,
      two homologous mouse genes, Zfp161 and Zfp161-rs1, were mapped to chromosome 17
      and the X chromosome, respectively. Mapping of Zfp161 confirms and extends a
      region of homology between distal mouse chromosome 17 and human 18p.

PMID- 9244433
TI  - Expression analysis and chromosomal assignment of the human SFRS5/SRp40 gene.
AB  - Alternative splicing plays a major role in the regulation of gene expression.
      SFRS5/SRp40 is a member of the serine/arginine (SR) protein family of regulators
      of alternative pre-mRNA splicing. We cloned the human SFRS5 cDNA and observed two
      major SFRS5 transcripts, an approximately 1.8-kb short form and an approximately
      3.3-kb long form, in both human and rat tissues. Both transcripts were detected
      in all human tissues examined, but there were notable tissue-specific differences
      in their relative abundance, the short form being most abundant in retina.
      Affinity-purified SFRS5 antisera recognized a single 40-kDa polypeptide in human
      and mouse retinal lysates. The abundant retinal expression of SFRS5 was not
      restricted to any specific cell type, since immunofluorescent labeling of human
      retinal sections identified the SFRS5 protein in nuclei of all three nuclear
      layers of the retina. The human SFRS5 gene was localized to human chromosome
      14q24 by fluorescence in situ hybridization and PCR analysis of a human/hamster
      somatic cell hybrid panel.

PMID- 9244434
TI  - A complete YAC contig and cosmid interval map covering the entirety of human
      Xq21.33 to Xq22.3 from DXS3 to DXS287.
AB  - We have produced a physical map that covers the entirety of Xq21.33 to Xq22.3,
      from DXS3 to DXS287, approximately 15-17 Mb of the proximal long arm of the human
      X chromosome. This region has already been shown to contain a number of genes
      involved in genetic disorders, some of which have yet to be cloned. The physical
      map consists of a contig of 420 yeast artificial chromosome (YAC) clones ordered
      with respect to 142 DNA markers, approximately one probe every 110 kb. Forty
      three YACs from across the contig have been used to isolate 2019 cosmids that
      have been mapped into 87 intervals, and 667 of these clones are positive for at
      least 1 single-copy marker. These YACs and cosmids have been used to confirm data
      from other published contigs that map to the region. The physical map described
      here constitutes the first step toward a complete transcriptional map of the
      region.

PMID- 9244435
TI  - Escape from X inactivation of two new genes associated with DXS6974E and
      DXS7020E.
AB  - Most genes on the X chromosome undergo "inactivation," being transcribed from
      only one copy in female somatic cells, but several human genes have been shown to
      be expressed from both the active and the otherwise inactivated homologue. To
      assess further the fraction and location of genes that escape inactivation, we
      have analyzed the inactivation status of a set of 73 expressed sequence tags that
      were derived from the sequencing of cDNA collections and mapped to the X
      chromosome. Of 33 that were expressed in cultured cells, as assessed by reverse
      transcription and PCR, 4 (about 12%) were transcribed from both the active and
      the inactive X chromosome. Two, RPS4 and PCTAIRE1, are already known to escape
      inactivation; the other 2, of unknown function, include a short cDNA with a full
      open reading frame and a transcript with no detectable open reading frame. They
      map, respectively, to Xp11.3-p11.4 and Xp22.2; both regions were previously
      reported to encode sequences transcribed from the inactive X. Neither transcript
      has a corresponding sequence on the Y. Thus, they exhibit double dosage in
      females compared to males, and inactivation status may be inconsequential for
      these transcribed sequences.

PMID- 9244436
TI  - Three genes encoding zinc finger proteins on human chromosome 6p21.3: members of
      a new subclass of the Kruppel gene family containing the conserved SCAN box
      domain.
AB  - Five genes encoding zinc finger proteins of the Cys2His2 (or Kruppel) family were
      identified by direct cDNA hybridization to YACs 753H12 and 638D7, which encompass
      a region of human chromosome 6p21.3 extending from just centromeric of the
      microsatellite marker D6S306 to telomeric of D6S1260. The genes span a distance
      of approximately 1750 kb. The complete cDNA sequence, genomic structure, and
      tissue distribution of three of the zinc finger proteins, LD65/ZNF165, ZNF192
      (previously called LD5-1), and ZNF193, are described. The three zinc finger
      proteins do not contain either Kruppel-associated box (KRAB) A or KRAB B domain,
      present in about one-third of all Kruppel-type zinc finger proteins (E. J.
      Bellefroid et al., 1991, Proc. Natl. Acad. Sci. USA 88: 3608-3612). The three
      zinc finger proteins do contain the conserved SCAN box domain (A. J. Williams et
      al., 1995, J. Biol. Chem. 270: 22143-22152). SCAN boxes are found in eight other
      genes in the GenBank database, five of which are also in the Kruppel family of
      zinc finger proteins lacking KRAB A and B domains and thereby define a new
      subclass of zinc finger proteins. In addition, three polymorphisms were
      identified in ZNF192, one of the zinc finger proteins. One of the three
      polymorphisms, Pro163Leu, is the second proline in a proline cluster (PEPP) in a
      region separating the SCAN box from the zinc finger motifs.

PMID- 9244437
TI  - High-resolution recombinational map of mouse chromosome 16.
AB  - Five intersubspecific backcrosses and an intercross were used to establish a sex
      averaged recombinational map spanning 56 cM across most of mouse Chromosome 16
      (Chr 16). A total of 123 markers were ordered using an interval mapping approach
      to identify 425 recombination sites in a collection of 1154 meioses from 1155
      progeny generated in the six crosses. The markers include the 10 "classic" Chr 16
      reference markers, 26 additional genes or transcripts including two phenotypic
      markers (Pit1dw and Kcnj6wv), and 87 simple sequence length polymorphisms
      (SSLPs). One set of monozygotic twins was detected among the 304 meioses mapped
      to highest resolution. The reference markers and SSLPs allow the map to be well
      integrated with existing maps of Chr 16. The average distance between crossover
      sites is less than 500 kb for most chromosomes, making this collection of
      recombinant chromosomes useful as a binning and ordering resource for YAC-based
      physical map assembly on Chr 16.

PMID- 9244438
TI  - Genomic organization and chromosomal localization of the mouse telencephalin
      gene, a neuronal member of the ICAM family.
AB  - Telencephalin is a cell adhesion molecule belonging to the immunoglobulin (Ig)
      superfamily, whose expression is restricted to subsets of neurons in the
      telencephalon, the most rostral segment of brain. Of all the Ig superfamily
      molecules so far identified, the structure of telencephalin is most closely
      related to those of intercellular adhesion molecules (ICAMs)-1 and -3. Here we
      report the cloning, characterization, and chromosomal localization of the mouse
      telencephalin gene (Tlcn). The Tlcn gene spanned about 6.3 kb and consisted of 11
      exons. A signal peptide and individual nine Ig-like domains of telencephalin were
      encoded by a single exon, while the transmembrane and cytoplasmic regions were
      fused in a same exon. The primer extension technique was used to establish that
      the transcription initiation sites were located 92-95 bp upstream from the ATG
      start codon. DNA sequencing of the 5'-flanking region revealed the presence of a
      strong initiator element for TATA-less genes, two CAAT boxes, and numerous
      potential transcription factor binding sites including four E-box and two N-box
      sequences. Interspecific backcross analysis demonstrated that the Tlcn gene was
      mapped in the proximal region of mouse chromosome 9 in close vicinity to the Icam
      1 gene, suggesting that Tlcn and Icam-1 are derived from a common ancestral gene
      by gene duplication.

PMID- 9244439
TI  - Evidence of linkage to 6p23 and genetic heterogeneity in nonsyndromic cleft lip
      with or without cleft palate.
AB  - Nonsyndromic cleft lip with or without cleft palate (CL+/-P) is a congenital
      orofacial anomaly that derives from an embryopathy with failure of nasal process
      and palatal shelves fusion. CL+/-P is one of the most common malformations,
      affecting 1/700-1/1000 live births among Caucasians. Early investigations have
      suggested that a clefting gene may be located on the short arm of chromosome 6
      (6p), as well as in other regions. In this study, we analyzed a large sample of
      families by using eight PCR markers that map on chromosome region 6p23-p24. The
      admixture test, as implemented in the HOMOG program, was significant when tested
      against multipoint data (alpha = 0.60, P value 0.00004); the lod score
      calculated, assuming heterogeneity, was 3.60 at 1 cM telomeric to D6S259. Taken
      together these data demonstrate the presence of a locus for CL+/-P in the 6p23
      chromosome region.

PMID- 9244440
TI  - Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a
      member of the chitinase protein family and marker for late stages of macrophage
      differentiation.
AB  - We have previously reported that the expression of HC gp-39, a 39-kDa secretory
      glycoprotein and member of the chitinase protein family, is associated with late
      stages of monocyte to macrophage maturation. To allow further investigations of
      its unique expression pattern and to facilitate studies on the regulation of this
      "marker gene," we characterized the genomic organization of the HC gp-39 gene
      (HGMW-approved symbol CHI3L1) and cloned its 5'-proximal promotor region. The
      gene is composed of 10 exons distributed over an 8-kb region. Two transcriptional
      initiation sites located 82 and 126 nucleotides upstream of the ATG start codon
      were identified using primer extension and S1 nuclease protection assays. We
      sequenced 1.3 kb of the 5'-flanking region and identified a variety of putative
      regulatory elements.

PMID- 9244441
TI  - Heterogeneity in rates of recombination in the 6-Mb region telomeric to the human
      major histocompatibility complex.
AB  - Analysis of 784 informative meioses in the CEPH pedigrees revealed a total of 22
      recombination events having occurred in the 6-Mb region between D6S265 (70 kb
      centromeric of HLA-A) and D6S276. These 22 breakpoints were localized with
      respect to anonymous polymorphic markers, leading to a detailed genetic map of
      the region telomeric to the human major histocompatibility complex. A nonrandom
      pattern of recombination was observed throughout this region: the low
      recombination rate of 0.19% within the 4-Mb interval centromeric to the HLA class
      I-like candidate gene for hemochromatosis indeed contrasts with the approximate
      1% rate observed within the most telomeric two megabases. This reduced rate of
      recombination may be due to selective constraints depending on environmental
      factors related to immunity and iron status or to structural variations hampering
      proper meiotic pairing of homologous sequences. Population data from other human
      genome segments are now needed to determine whether linkage disequilibrium
      extending over 4 Mb is unique to this region.

PMID- 9244442
TI  - Data note system for capturing laboratory data.
AB  - The complexity of genome data limits the usefulness of traditional database
      management systems. The highly interconnected structure of genome data can be
      captured in a data representation language based on the mathematical formalism of
      graphs. We have tailored graphs for describing genome data and have developed a
      database management system, called the Data Note System, for developing small
      databases to capture data from genome laboratories. To simplify the use of the
      Data Note System, a series of tools with graphical user interfaces has been
      developed. The system is designed to be easy to install and use by novice
      database developers with a minimal amount of computer expertise. We describe the
      tools and present examples of their use. The system consists of a storage
      facility, a schema editing tool to simplify the design of small databases, and
      three tools for data entry and querying.

PMID- 9244443
TI  - Genomic structure and chromosomal localization of the gene encoding translin, a
      recombination hotspot binding protein.
AB  - Human Translin is a novel DNA end binding protein that specifically recognizes
      consensus sequences at the breakpoint junctions in chromosomal translocations,
      mostly involving immunoglobulin (Ig)/T-cell receptor gene segments, in human
      lymphoid neoplasms. We have recently cloned a full-length human Translin cDNA
      using peptide sequence information obtained from the purified protein. From
      comparisons of the amino acid sequences in humans and other vertebrates, we
      conclude that Translin has been highly conserved during evolution, especially at
      the leucine zipper motif and the basic region, which is thought to be the DNA
      binding domain. Analysis of the human and mouse Translin genes revealed that they
      have identical genomic structures consisting of six exons, five introns, and a GC
      rich upstream region. In situ hybridization and physical mapping of somatic cell
      hybrids allowed localization of the gene to human chromosome 2q21.1.

PMID- 9244444
TI  - Integrated radiation hybrid map of human chromosome 2p13: possible involvement of
      dynactin in neuromuscular diseases.
AB  - The genes for the human neuromuscular diseases limb-girdle muscular dystrophy
      type 2B (LGMD2B) and Miyoshi myopathy are located on chromosome 2p13-p14, and two
      neuromuscular mutations of the mouse have been mapped to regions homologous to
      human chromosome 2p13 by conserved synteny, wobbler (wr) on proximal Chr 11 and
      motor neuron degeneration 2 (mnd2) on Chr 6. Neither one is a mouse homologue of
      LGMD2B. Recently the gene DCTN1, coding for the large subunit of the cytoskeletal
      protein dynactin, was shown by FISH to be located in this region and therefore
      should be considered a candidate for all these disease genes. Here we present
      mapping data based on radiation hybrid and physical mapping that more precisely
      define the location of nine genetic markers in the critical region and the
      homology relationship of human chromosome 2p with mouse proximal Chr 11 and Chr
      6. The human dynactin gene was mapped between markers TGFA and D2S1394, implying
      that the mouse dynactin gene Dctn1 is located on Chr 6, distal to mnd2. Thus
      DCTN1/Dctn1 is a candidate for LGMD2B but not for mnd2 or wr.

PMID- 9244445
TI  - Assignment of the human gene for smoothelin (SMTN) to chromosome 22q12 by
      fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 9244446
TI  - Localization of the gene encoding the Ran-binding protein RanBP2 to human
      chromosome 2q11-q13 by fluorescence in situ hybridization.

PMID- 9244447
TI  - Isolation of DNA from the centromere of human chromosome 7 by microdissection.
AB  - Centromeres remain the least characterized regions of human chromosomes because
      they have a very high content of repetitive DNA. Here, we describe a
      microdissection library from the centromeric region of human chromosome 7 and its
      use for generating sequence tagged sites (STSs). The library contains about 1500
      clones with an average insert size of 150 bp and only about 15% of the clones
      harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found
      to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus
      confirming the origin of the library. A number of clones not containing known
      repetitive DNA were used to generate STSs that identified yeast artificial
      chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map.
      One STS is located between the two Genethon genetic markers closest to the
      centromere on the q side. Another STS was located 3-4cM away in 7q11.2, while a
      third identified YACs containing both low-copy and alphoid sequences that are not
      yet mapped but are clearly centromeric. The library therefore comprises a
      collection of sequences from the centromeric region of chromosome 7 that can be
      used to generate STSs and to map the entire centromeric region.

PMID- 9244448
TI  - Polymorphism of the nucleolus organizer region (NOR) on the putative sex
      chromosomes of Arctic char (Salvelinus alpinus) is not sex related.
AB  - Polymorphism of the nucleolus organizer region (NOR) on the putative sex
      chromosomes of Arctic char (Salvelinus alpinus) was examined using conventional
      cytogenetic and molecular techniques. Variation was observed in the number, size
      and position of rDNA loci on the sex pair. Fluorescence in situ hybridization
      (FISH) analyses showed that the sex chromosomes of Arctic char lack the
      repetitive DNA sequences (Mbol/BglII family) that are a prominent feature of the
      sex chromosomes of lake trout (S. namaycush). Southern analyses of genomic DNAs
      using an rDNA fragment as probe revealed extensive restriction fragment length
      polymorphism (RFLP) variation among individuals. Despite the presence of
      variation in all aspects of this rDNA locus, no sex-specific differences were
      detected. Repetitive DNAs (multicopy rDNA as in Arctic char or tandem repetitive
      DNA as in lake trout) appear to play important but different roles in the
      evolution of the sex chromosomes in these species.

PMID- 9244449
TI  - Telomeric sequences localization and G-banding patterns in the identification of
      a polymorphic chromosomal rearrangement in the rodent Akodon cursor (2n=14,15 and
      16).
AB  - Akodon cursor is an exceptional example of high chromosomal variability,
      displaying diploid numbers from 14 to 16 and fundamental numbers (FN) from 18 to
      26 as the result of a complex rearrangement in par 1 and pericentric inversions
      in three autosomal pairs. The difference in the diploid number is due to the
      presence of a large metacentric pair 1 in the 2n=14 karyotype, a large
      metacentric 1 and two different submetacentrics (1a and 1b) in 2n=15 and 1a and
      1b submetacentric pairs in homozygosis in the 2n = 16 karyotype. Chromosomes 1a
      and 1b share homology with the short and long arms of the large metacentric 1
      respectively. In this paper, evidence based on fluorescence in situ hybridization
      (FISH) with telomeric sequences and G-banding indicates that pericentric
      inversions and fusion of chromosomes 1a and 1b are the probable rearrangements
      giving rise to the large metacentric 1.

PMID- 9244450
TI  - Differences of histone H4 acetylation and replication timing between A and B
      chromosomes of brachycome dichromosomatica.
AB  - Differences are demonstrated between A (transcriptionally active) and B
      (transcriptionally inactive) chromosomes that are characterized by a different
      level of histone H4 acetylation and a different timing of DNA replication. These
      differences between the chromatin of A and B chromosomes were found after
      immunolabelling of chromsomes of Brachycome dichromosomatica with antibodies
      specific for different acetylated forms (lysine 5, 8, 12 and 16) of histone H4.
      In contrast to the A chromosomes, which are labelled brightly in their entirety,
      the transcriptionally inactive B chromosomes are faintly labelled with antibodies
      against H4Ac5 and H4Ac8. No such difference between the chromosomes is found
      after immunostaining with the other antibodies H4Ac12 and H4Ac16. Analysis of DNA
      replication timing in root-tip meristems suggests that B chromosomes are labelled
      late in S-phase compared with A chromosomes. After C-banding the B chromosome
      appeared to have a similar amount of heterochromatin to the A chromosomes.

PMID- 9244451
TI  - Multiple repetitive DNA sequences in the paracentromeric regions of Arabidopsis
      thaliana L.
AB  - Nine repetitive DNA sequences, present in the haploid Arabidopsis thaliana genome
      in 7-300 copies, were hybridized in situ to metaphase and interphase chromosomes.
      Every sequence was detected on all five chromosome pairs, but was not evenly
      dispersed over the genome. Clusters of signals were found in particular regions
      of the centromeric heterochromatin, and each sequence showed a characteristic
      distribution pattern. Some sequences hybridized more strongly on different
      chromosomes, reflecting chromosome-specific amplification or the presence of
      homologous sequences. No hybridization signals could be detected on euchromatic
      regions. In situ hybridization on extended chromatin fibres showed that the pAL1
      repeats are interrupted by another repetitive DNA sequence. A cosmid subclone
      (74A) contained a (GA)38 microsatellite motif, and hybridization with a (GA)
      oligonucleotide revealed that most of the hybridization sites of 74A correspond
      to the distribution of this microsatellite motif. The results show that the
      paracentromeric heterochromatin of A. thaliana chromosomes is composed not only
      of the tandemly arranged 180-bp repeat family pAL1/pAtMr, but also of some other
      repetitive sequences, thus giving a better understanding of the organization of
      sequences at the centromeres of A. thaliana.

PMID- 9244452
TI  - Application of three different methods to analyse fibre-FISH results obtained
      using four lambda clones from the porcine MHC III region.
AB  - Four lambda clones (lambda G11, lambda C4, lambda G14 and lambda G17) from the
      porcine MHC class III region were labelled with either biotin-14-dATP or
      digoxigenin-11-dUTP and hybridized in two different combinations to DNA fibres.
      The latter were prepared from agarose-embedded porcine peripheral lymphocytes
      lysed with proteinase K, then spread and fixed on poly-L-lysine-coated slides.
      Hybridization signals thus obtained confirm the order of the clones previously
      reported using pulsed-field gel electrophoresis (PFGE). Measurements of probe
      sizes, gap distances between probes and total length of DNA encompassing the
      probes were made. Three different methods, namely relative length, Watson-Crick
      standard and probe size standard-based conversions, were used to estimate the
      parameters in kilobases. These methods of data conversion were compared with each
      other and with the available PFGE data, and their utility and accuracy were
      evaluated.

PMID- 9244453
TI  - Zoo-fluorescence in situ hybridization analysis of human and Indian muntjac
      karyotypes (Muntiacus muntjak vaginalis) reveals satellite DNA clusters at the
      margins of conserved syntenic segments.
AB  - Zoo-fluorescence in situ hybridization (FISH) with human whole chromosome
      specific paint probes revealed extensive homoeologies between Indian muntjac
      (2n=6, 7 female, male) and human karyotypes (2n=46). Forty-two conserved syntenic
      segments, corresponding to all human chromosomes except the Y chromosome,
      produced a near-complete coverage of the muntjac complement and revealed margins
      of interspecific segmental homoeology. To test the hypothesis that interstitial
      satellite DNA loci, illuminated by a Chinese muntjac C5-satellite probe in Indian
      muntjac chromosome arms, mark ancestral fusion points (Lin CC, Sasi R, Fan YS,
      Chen Z-Q (1991) New evidence for tandem chromosome fusions in the karyotypic
      evolution of the Asian muntjacs. Chromosoma 101: 19-24), we combined Zoo-FISH
      with C5 satellite mapping. Twenty-six interstitial satellite DNA loci were
      detected in the haploid Indian muntjac genome and were found to co-localize with
      the margins of conserved human/Indian muntjac syntenic segments. These results
      were confirmed by two-colour FISH and are in accordance with the tandem fusion
      hypothesis for Indian muntjac chromosomes. Furthermore, conserved syntenic
      segment combinations detected in pig, cattle and Indian muntjac Zoo-FISH maps
      reveal ancestral artiodactyl chromosomes.

PMID- 9244454
TI  - Fluorescence in situ hybridization of ribosomal DNA to mitotic chromosomes of
      tsetse flies (Diptera: Glossinidae: Glossina).
AB  - Ribosomal genes were mapped in Glossina austeni, G. brevipalpis, G. f. fuscipes,
      G. m. submorsitans, G. p. palpalis, G. pallidipes and G. tachinoides on mitotic
      chromosomes by fluorescence in situ hybridization (FISH) using Drosophila hydei
      genomic clones that contain the 28S ribosomal DNA. In all species except G.
      brevipalpis, the ribosomal genes were located on the long arm of autosome L1. The
      Y chromosomes of G. pallidipes and G. p. palpalis showed additional hybridization
      signals. Supernumerary chromosomes were found in G. austeni, G. brevipalpis and
      G. pallidipes. The C-banding pattern obtained by in situ hybridization was
      compared with Giemsa C-banding patterns that were published previously. The
      karyotype of G. brevipalpis was found to differ from that of other Glossina
      species, with either two or three FISH signals being obtained with a ribosomal
      probe, depending on the individual analysed. The rDNA genes are the first
      physically mapped markers in tsetse flies and will be useful for mapping
      approaches.

PMID- 9244455
TI  - Analysis of NORs and NOR-associated heterochromatin in the mussel Mytilus
      galloprovincialis Lmk.
AB  - The chromosomes of the mussel Mytilus galloprovincialis were analysed by means of
      chromomycin A3 (CMA), distamycin A/DAPI (DA/DAPI), DAPI/actinomycin D (DAPI/AMD)
      and chromomycin A3/distamycin A/DAPI (CDD) fluorescence banding techniques, C
      banding, silver staining, N-banding and in situ hybridization with 18S+28S rDNA
      and telomere probes. 18S+28S rDNA clusters were located on the telomeres of two
      pairs of submeta/subtelocentric chromosomes. The nucleolar organizing regions
      (NORs) were associated with bright CMA fluorescence, dull DAPI fluorescence and C
      and N-positive bands, but not all four NOR-associated heterochromatin bands
      showed bright CMA fluorescence in a given cell; intra- and interindividual
      variability was found in this character. Additional non-ribosomal C-bands did not
      show any differential fluorescent behaviour.

PMID- 9244456
TI  - Chromosomal localization of alpha-galactosyltransferase 1 (GGTA1) and elongation
      factor 2 (EEF2) genes in river buffalo by FISH.

PMID- 9244458
TI  - Rect references.

PMID- 9244457
TI  - Localization of the SCO-spondin gene to cattle chromosome 4.

PMID- 9244459
TI  - [Studies on the essential oils in Ligusticum chuanxiong Hort. of different
      habitats and species].
AB  - Constituents of the essential oils obtained from Chuanxiong, Yungxiong, Fuxiong,
      Xixiong and "Chuanxiong" of Japan were analysed by GC-MS. Ninety-six compounds
      including ligustilide, etc. were identified. Their percentages in the oils were
      given.

PMID- 9244460
TI  - [How to export orthodoxy to the South. The World Bank and health care reform in
      Uganda].

PMID- 9244461
TI  - [Bottling of mineral water for therapeutic use. Possibility of physical
      treatment].

PMID- 9244462
TI  - [Salmonellosis caused by unusual vehicles in Molise].

PMID- 9244463
TI  - [Presence of Listeria spp. in vegetables].

PMID- 9244465
TI  - [Role of starlings in the diffusion of Listeria monocytogenes and Listeria spp].

PMID- 9244464
TI  - [Hygienic quality of a typical Italian cheese: mozzarella di bufala campana].

PMID- 9244467
TI  - [Nutritional intervention in overweight subjects with hypercholesterolemia.
      Reduction of blood cholesterol by guided diet therapy].

PMID- 9244466
TI  - [Antioxidants in the diet of a general population].

PMID- 9244468
TI  - [Human toxocariasis: biology of the parasite and current diagnostic
      possibilities].

PMID- 9244469
TI  - [Accidents caused by gas equipment and carbon monoxide poisoning in dwellings of
      the Lombardy region in the period October 1955-April 1996].

PMID- 9244470
TI  - [Indoor chemical pollutants and their effects on health].

PMID- 9244471
TI  - Bacterial infection in patients with cancer: focus on prevention.

PMID- 9244472
TI  - Role of diet in cancer hard to study, expert says.

PMID- 9244473
TI  - Proceedings of the 6th International Course on Peritoneal Dialysis. Vicenza,
      Italy, May 20-23, 1997.

PMID- 9244474
TI  - Glove Powder--The Hazards which Demand a Ban. Proceedings of a meeting. London,
      United Kingdom, May 1996.

PMID- 9244475
TI  - Encyclopedia of the mouse genome VI. January 1997.

PMID- 9244476
TI  - Encyclopedia of the mouse genome VI. Master locus list.

PMID- 9244477
TI  - [Medical use of stepwise adaptation to hypoxia].
AB  - The paper outlines N. N. Sirotinin's concept of the use of stepwise adaptation to
      diminished inspired air pO2 as a non-drug agent for the prevention and treatment
      of diseases whose pathogenesis hypoxia and their subsequent rehabilitation play a
      definite role in. A comprehensive study of the impact of reduced pO2 on man and
      animals has defined the magnitude of its ambient air changes under which a human
      being may adapt himself to hypoxia, it characterized five stages of hypoxic
      hypoxia and concluded that an adaptative process is effective in subcompensated
      and compensated hypoxia. The paper describes the stepwise adaptation proposed by
      N. N. Sirotinin to treat diseases chiefly caused by hypoxia and his three
      identified stages of adaptation-a process considered by N. N. Sirotinin and his
      pupils as a natural response of the respiratory functional system to the changing
      magnitude of the usually acting stimuli-reduced arterial blood oxygen and carbon
      dioxide tension. The mechanisms responsible for the favourable impact of stepwise
      hypoxic adaptation, which are the basis for its wide use in medicine,
      occupational hygiene, and sports are presented. Data on the development of N. N.
      Sirotinin's idea and its medical application in Russia and foreign countries are
      given.

PMID- 9244478
TI  - [Effects of hypoxia on the activity of the sympathetic-adrenal system].
AB  - Experiments on rat males (120-150 g b.weight) inhaling air with oxygen
      concentration 16, 14, 12, 10, 8 and 5.3% for an hour and placed at the altitudes
      2000, 3500 and 3200 in above the sea level in the mountains demonstrated that
      adrenaline and noradrenaline concentrations in the brain tissues, adrenals, blood
      and urine depend on the intensity and duration of the exposure to low pO2 in the
      air. Adaptation to hypoxia provokes a significant increase of noradrenaline in
      the adrenals, cerebral cortex, hypothalamus and biological fluids.

PMID- 9244479
TI  - [Response of the functional system of respiration to the cyclic changes of the
      hormonal state in women].
AB  - Examinations of the respiration, blood flow, blood respiratory function, oxygen
      intake, mental and physical performance of 116 female athletes going in cyclic
      and acyclic sports during a menstrual cycle significantly altering the female
      status ascertained that the status of the respiratory system varied with these
      changes. High economic benefits of respiratory function and oxygen regimens of
      the body, high breathing reserves in the postmenstrual and postvalutional phases
      of a menstrual cycles were found to make the female athletes show higher working
      capacities in these phases. In addition to instrumental determinations, computer
      aided simulation of the body's oxygen regimens and respiratory functional system
      was used to calculate oxygen parameters and the magnitude of respiratory
      functional changes during a menstrual cycle.

PMID- 9244480
TI  - [Possibilities of normobaric hypoxic training in rehabilitation of patients with
      chronic bronchitis].
AB  - To provide evidence for the potentialities of normobaric hypoxic training (NHT),
      oxygen cascades from the lung to tissues and responses to hypoxic and hypercapnic
      stimuli were analyzed in chronic bronchitis patients with Stages 1, 2, and
      respiratory failure. Since at Stages 2 and 3, compensatory responses are
      substantially decreased, there is arterial, and occasionally, venous hypoxemia,
      NHT is contraindicated in these patients. Compensatory responses are preserved
      only during early stages 0 and 1 respiratory failure, showing it expedient to
      employ NHT. NHT regimens (as many as 20 sessions) used in these patients improved
      the patients' condition and physical activity, normalized ventilation function.
      However, the concurrent diseases exacerbated in some cases. Medical monitoring is
      needed when the NHT regimen is used.

PMID- 9244481
TI  - [Nikolai Nikalaevich Sirotinin and his school].
AB  - In a brief review of 50-year scientific activity of professor N. N. Sirotinin and
      his students the authors emphasize that this broad-minded scientist contributed
      to development of such disciplines as microbiology, pathophysiology, high
      altitude, aerospace medicine. However, his main goal was evolution of reactivity
      and resistance, approaches to perfection of human health and performance. Much
      attention was paid to effects of low partial oxygen pressure on human and animal
      body, to hypoxic states of different origin. Methods of hypoxytherapy and hypoxic
      training are widely used in Russia and abroad. The contribution of academician N.
      N. Sirotinin to modern pathophysiology, high-altitude and aerospace physiology,
      internal and sport medicine is highly appreciated in Russia.

PMID- 9244482
TI  - [Use of normobaric hypoxic training in obstetrics].
AB  - Literature data and own investigations allowed the authors to make a conclusion
      on positive therapeutic effect of normobaric interval hypoxic training (NBIHT) in
      patients with hypoxia-induced diseases. Comparison of pregnancy in females at
      high risk of gestosis who underwent NBIHT in the second and third trimester
      versus those who were treated conventionally showed more successful delivery,
      less frequent occurrence of nephropathy, fetal hypoxia, premature labor, better
      physical condition of newborns in the group of NBIHT gravidas.

PMID- 9244483
TI  - [Changes in lymphocyte cytochemical markers in radiation-exposed patients under
      mountain conditions].
AB  - It is shown that 24-day rehabilitation in the mountains reduced general
      sensitization in subjects exposed to radiation after the Chernobyl accident. The
      assessment of lymphocyte population and functional activity (lysosomal,
      mitochondrial, mitotic) by their markers (acid phosphatase, succinate
      dehydrogenase, DNA) indicated lowering of B-lymphocyte count, T-killers,
      increased count of o-lymphocytes, DNA in all lymphocyte populations, a rise in
      the activity of SDG and acid phosphatase. Subjects from the Chernobyl rescue
      teams living in high altitudes for 3-15 years after the accident had low T
      lymphocyte but high o-lymphocyte counts, stable SDG, enhanced activity of acid
      phosphates in T-killers. The fact of lymphocyte populations increase, stimulation
      of their activity observed in the end of the radiation-exposed subjects,
      rehabilitation gives grounds for further investigations of beneficial effect of
      mountain climate on irradiated body, of relevant indications and
      contraindications.

PMID- 9244484
TI  - [Possibility of correction of the hormonal state of girls by hypoxic training].
AB  - Hormonal effects on the functional status and working capacity were found in
      girls with juvenile dysfunctional uterine hemorrhage who had been exposed to
      ionizing radiation in early childhood, in those with primary hyperthyroidism and
      healthy athletic girls in different phases of a menstrual cycle. Whether the
      hormonal status might be corrected by interval hypoxic training was examined.
      There was a relationship of respiratory functional changes to the phases of a
      menstrual cycle in healthy girls. Impaired external respiratory function, blood
      flow, and blood respiratory function, lower oxygen consumption were found in
      girls who had been victims of the Chernobyl accident and respiratory functional
      changes were detected in patients with hypothyroidism. It was ascertained that
      interval hypoxic training was an effective alternative to mountain training, that
      it promoted higher aerobic and anaerobic productivity and special working
      capacity in athletes. An interval hypoxic training course was found to
      substantially improve oxygen regimens in girls with secondary anemia, to elevate
      hemoglobin levels to normal values, to recover normal ovarian function. It also
      enhanced the production of thyroid hormones, normalized oxygen consumption,
      improved the patients' condition, increased physical and mental performance in
      patients with hypothyroidism.

PMID- 9244485
TI  - [Use of hypoxic training in sports medicine].
AB  - Examinations of high-quality athletes during their hypoxic adaptation under low
      pressure mountain conditions and under normal pressures during normobaric
      interval hypoxic training included into the planned sports preparation of
      athletes indicated changes in respiration, blood flow, blood respiratory
      function, tissue oxygen consumption, aerobic productivity and working capacity.
      The use of a combined regimen was shown to have benefits in enhancing aerobic
      productivity and general working capacity, this was applied in sports medicine
      while training athletes for important tournaments.

PMID- 9244486
TI  - [Adaptation to hypoxia as a factor enhancing work capacity].
AB  - The results of applying N. N. Sirotinin's concept of the use of hypoxic
      adaptation to enhance working capacity are given. There is evidence for the
      efficiency of adaptation of trotters to two hypoxias: to hypoxic hypoxia (in the
      midmountains) and to exercise hypoxia (during interval training under the
      conditions of Moscow) for increasing their performance. These studies
      demonstrated that in the midmountains, the trotters had more infrequent
      respiration, increased respiratory and minute respiratory volumes which were more
      obvious by the end of a monthly mountain stay. The monthly training of trotters
      significantly altered hemoglobin levels and erythrocyte counts. Correction of the
      respiratory system via adaptation to decreased p1O2 improved good time in
      trotters: the speed increased by 0.41 versus by 0.18 m/sec in the controls. The
      average record of experimental horses significantly increased and was equal to 2
      min 09.7 sec for a 1600-m distance while the control horses had 2 min 11.1 sec.
      The use of interval exercises during training produced positive changes in the
      systems of expiratory respiration, blood flow, blood, tissue metabolism. Blood
      oxygen transport function improved in trotters after interval training. This
      training markedly improves the fast qualities in trotters.

PMID- 9244487
TI  - [Analysis of the effectiveness of interval hypoxic training in rehabilitation of
      apparently healthy persons: an individual approach].

PMID- 9244489
TI  - [Current pathophysiology as an experimental, fundamental and integrative
      biomedical science].

PMID- 9244490
TI  - [Hypothesis about similar processes in living organisms].

PMID- 9244488
TI  - [Results of studies of regulatory mechanisms of hematopoiesis in health and
      disease].
AB  - Local and distant hemopoietic regulatory mechanisms were studied under various
      emergencies (immobilization, cytostatic injection, radiation, etc.). There were
      common processes (cell migration, destruction, T-lymphocyte accumulation,
      activation of the microenvironment and hemopoietic precursors) forming the local
      basis for compensatory and adaptive reactions of bone marrow hemopoietic tissue.
      Emphasis is laid on the association of local mechanisms with the neuroendocrine
      system which inevitably becomes activated under extreme exposures. On exposure to
      irritants having no myeloinhibitory effect, neurotransmitters and hormones,
      mainly glucocorticoids and catecholamines cause the development of erythro- and
      granulocytopoietic hyperplasia due to stimulation of the hemopoiesis-inducing
      microenvironment (HIM). Under hemopoiesis-suppressing influences, catecholamine
      induced activations of HIM's resistant elements is accompanied by simultaneous
      inhibition of hemopoietic cells and HIN's factors damaged by an irritant. Under
      these conditions hemopoietic separation caused by the heterogeneous effect of
      transmitters on the cell leads to imbalance of hemopoietic precursor
      proliferation and differentiation and, finally, to delayed hemopoietic tissue
      regeneration. At the same time, the neuroendocrine system does not seem to play a
      leading role as compared to the control intact hemopoiesis.

PMID- 9244491
TI  - [Proteins from murine embryonal and germ cells, interacting in vitro with
      Oct3/4].

PMID- 9244492
TI  - [Serial staining (common-G-NOR-C) of yellow-bellied lemming (Lemmus chrysogaster
      J.A. Allen, 1903) chromosomes].

PMID- 9244493
TI  - [Molecular systematic of hedgehogs (Erinaceidae, Insectivora) of the northeastern
      palearctic: testing the new method].

PMID- 9244494
TI  - [Structure of blocks of pericentromeric heterochromatin at chromosomes 3 and 4 in
      pseudonurse cells from larvae of Drosophila melanogaster line OTU].

PMID- 9244495
TI  - [Disruption of plasma cell membrane permeability for Ca2+ ions in radiation
      induced apoptosis of thymocytes].

PMID- 9244496
TI  - [Effect of suppressing oxidative metabolism in cells by pulsed irradiation from
      an He-Ne-laser depends on the duration of the dark period between pulses].

PMID- 9244497
TI  - [Soliton system in the Fitzhugh-Nagumo equation system: dynamics of a a rotating
      spiral wave].

PMID- 9244498
TI  - [Effect of vasopressin on the hyaluronate hydrolase system in the amphibian
      bladder].

PMID- 9244499
TI  - [Prediction of tolerance of longitudinal linear head-to-tail accelerations of
      short duration (up to 5 seconds)].
AB  - The paper is focused on prediction of loss of consciousness and grey-out during
      short (up to 5 s) impulses of longitudinal head-to-tail accelerations with high
      buildup gradients (more than 50 m/s3). This is a poorly explored region of
      exposure on the borderline between impulsive and maneuvering accelerations of the
      modern aircraft. On the basis of comparing the prediction with available
      experimental data, prognostic potentials of various modifications of criterion
      which includes the maximum allowable values of velocity in this range of exposure
      are demonstrated.

PMID- 9244501
TI  - [Hemodynamic structure of antiorthostatic reactions: relationship of mechanical
      activity of the heart and arterial pressure].
AB  - In acute experiments with antiorthostatic rats tilt-induced changes in the
      parameters of cardiac activity (left ventricle systolic pressure (LVPs), its
      first derivative dp/dt, end-diastolic pressure (EDP) were compared in relation to
      the directionality and extent of systolic (sAP) and diastolic arterial pressure
      (dAP) shifts. Rise of the tilt angle by 15-45 degrees reduced sAP and dAP,
      increased LVPs and EDP and did not influence dp/dt. Changes in the cardiac
      parameters and AP were not unidirectional; sAP and dAP shifts were asynchronous.
      In a special experimental series, higher tilt angle was found to bring about
      opposite changes in cardiac ejection (CE) and total peripheral resistance (TPR).
      Growth in CE was concurrent to a progressive decline in TPR. Discussed is the
      response of the vascular system to antiorthostasis the unique character of which
      is vasodilatation.

PMID- 9244500
TI  - [Lipid peroxidation and activity of diagnostically significant enzymes in
      cosmonauts after flights of various durations].
AB  - Concentrations of the products of peroxide oxidation of lipids (POL), indices of
      the system of antioxidant defence (SAD), and the activity of 13 diagnostically
      significant organic/tissue specific enzymes (DSE) were determined in blood serum
      of cosmonauts who had participated in short (5-9 days, n = 8), long (125-179
      days, N = 15), and superlong (241-366 days, n = 5) missions. To feature an
      interrelation of the indices under study, the canonical correlation analysis of a
      set of POL and SAP parameters and DSE activity was performed. Compared with pre
      flight values, changes in the POL and SAP parameters were significant in serum
      only after the long-duration missions. Signs of POL activation were noted
      following the superlong missions. After the long-duration missions increased was
      the activity (mainly, within the norm) of DSEs, specific for the organs and
      tissues functioning of which is stressed in the period of post-flight
      readaptation (skeletal muscles, myocardium, liver). After the superlong missions,
      the DSE activity either remained essentially unchanged or decreased. In all the
      tested groups, highly reliable correlations between POL, SAP, and the DSE
      activity, traditionally applied in clinical diagnostics, were observed. These
      advocate for the use of POL and SAP indices in medical diagnostics and prognosis
      of cosmonauts' health.

PMID- 9244502
TI  - [Changes in lipid contents of the myocardium in rats during physical loading
      after long-term hypokinetic stress].
AB  - During prolonged motor restraint rearrangement of the lipid bilayer of membranes
      in the aortic ventricle of the heart progresses in parallel to atrophy of its
      contractile system. This rearrangement is characterised by a decrease in
      cholesterol and an increase in relative content of unsaturated phospholipids,
      initially contributing to activation of the lipid-dependent enzymatic systems,
      and more effective electromechanical conjugation. However, subsequent
      accumulation of toxic products of lipids peroxidation indicative of disturbed
      adaptation mechanisms involved in stress-reaction resulted in damage to the
      myocardial membranes, variations in the bioelectrical properties and deteriorated
      contractility, and diastolic relaxation of the cardiac muscle. Consequently,
      heart adaptability to load was reduced in the period of readaptation after
      hypokinesia. On the background of energy deficiency with subdued synthesis of
      contractile muscle proteins, levels of cholesterol, triglycerides and especially
      free fatty acids went up. Along with lipid peroxides these agents disrupt
      functioning of subcellular organelles and limit adaptation potentials of
      deconditioned heart.

PMID- 9244503
TI  - [Effects of hypokinesia of different duration on electrolyte contents in muscle
      tissue of rats].
AB  - The study has demonstrated a significant increase in blood levels of potassium on
      Day 3 of hypokinesia. Sodium content and the sum of two ions were decreased on
      Day 3 and increased on Day 10 of the exposure. Significant changes in the calf
      muscles (musculus gastrocnemius), i.e. decreased potassium and increased sodium
      concentrations, were observed on Days 10, 30, 45, 70, 90, and 140. The total
      content of potassium and sodium ions remained reduced. Analysis of parameters
      characterising the ion gradients points to lowered activity of Na-K-dependent ATP
      ase, fewer number of ion-binding groups of tissue anions. In myocardium, these
      shifts were less pronounced and included an insignificant loss of potassium ions
      and gain in sodium ions the gradient of which was most significant on Days 10,
      30, and 45. The general trend of changes in the ion balance implies some unified
      mechanisms of the hypokinesia effects on the muscular tissue, associated with the
      disorders in energy metabolism, change in hormonal status, and activation of
      catabolic processes in immobilised body giving rise to deconditioning and
      asthenization.

PMID- 9244504
TI  - [Combined effects of hypokinesia and various doses of gamma irradiation on
      conditioned reflex activity in rats].
AB  - There has been studied the effect of 30-day hypokinesia (HK) and gamma-radiation
      at three non-lethal doses (3.5, 5.0, and 8.5 Gy) on elaboration of the motor
      defence reflex of active avoidance (RAA). Radiation-induced slowing-down of the
      RAA formation was in direct proportion to the dose applied. Modifying action of
      gamma-radiation on the hypokinesia effect showed up markedly only at the highest
      dose (8.5 Gy). Modifying action of HK with respect to the radiation effect can be
      assessed as insignificant; however, a downward trend was established in the rate
      of the reflex formation under the combined exposure to these factors.

PMID- 9244505
TI  - [Tissue basophils of the thyroid gland in separate and combined exposure to
      ionizing radiation and ethanol].
AB  - Experiments with male albino rats gave evidence that a single intraperitoneal
      injection of 15% ethanol at the doses of 0.28 and 2.25 g/kg resulted in enhanced
      elimination of biologically active substances by tissue basophils (TB) both due
      to intensified degranulation and greater number of TB in the thyroid gland.
      Single total exposure to ionizing radiation at the doses of 5, 10, and 20 Gy
      stimulated the functional activity of TB with simultaneous accumulation of
      biologically inactive substances. Radio modifying effect of ethanol with respect
      to thyroid TB consisted of an increase of their number and a decrease in the
      extent of degranulation which was not dependent on the sequence of radiation
      exposure and ethanol injection.

PMID- 9244506
TI  - [Medical aspects of prolongation of occupational longevity].
AB  - Rationale is given to the necessity of methodical approaches to extension of
      total and active periods of human life. Methods and measures intended to
      maintain/restore working capacity of human operator of automated working place
      are recommended.

PMID- 9244507
TI  - [Effects of enduracin on the level of cholesterol in flying personnel].

PMID- 9244508
TI  - [Use of low-frequency electric field in the rehabilitation of flying personnel].

PMID- 9244509
TI  - [Effects of low-intensity laser irradiation on physical endurance of rats].

PMID- 9244510
TI  - [Ultrastructure of the kidney in acute massive hemorrhage at moderate and high
      altitudes].

PMID- 9244511
TI  - [Errors in the elaboration of a simplified procedure of evaluation of physical
      work capacity (concerning the article by V.V. Timoshenkov, Modified technique to
      determine general physical work capacity of man during bicycle ergometry test.
      Aviakosm. i Ekolog. Med., 1996, Vol.30. No.3, pp.46-50.)].

PMID- 9244513
TI  - Joint Scientific Conference of the Canadian Society for Transfusion Medicine and
      the Canadian Red Cross Society. 23-26 May 1996. Abstracts.

PMID- 9244512
TI  - [Psychophysiological aspects of joint activity of crew members in special flight
      situations].
AB  - Findings of experimental studies of the psychophysiological peculiarities of
      crewmember interaction in emergency are presented. It is demonstrated that the
      developed psychophysiological recommendations on optimisation of data acquisition
      and processing, decision-making, inter-crew distribution of functions, mutual
      control and reservation allow a considerable increase of the probability of
      preventing in-flight emergency.

PMID- 9244514
TI  - [The combined action of ionizing radiation and sodium nitrate on bacterial
      cells].
AB  - The survival of bacterial cells Escherichia coli exposed to sodium nitrate (1-5
      M) simultaneously with 60Co gamma rays was shown to be smaller than that expected
      for independent addition of the effects induced by each of agents applied
      separately. The synergistic effect was quantitatively estimated by the factor k,
      which is the ratio of the isoeffective doses on the calculated additive survival
      curve and the experimental one. The dependencies of k on the exposition of
      combined action of gamma rays and different NaNO3 solutions (1, 3 and 5 M) are
      presented. It was demonstrated that the synergistic ratio k was increased with
      exposure duration increasing. It is suggested that in this case the synergistic
      effect may be related with the formation of some additional lethal damage due to
      NaNO3 radiochemical transformation products.

PMID- 9244515
TI  - [The joint action of nitrates and gamma radiation on the blood plasma proteinase
      inhibiting and antioxidative systems in rats].
AB  - The separate and combine influence of nitrates (40 mg of natrium nitrate) 100 g
      of body mass during 60 days) and gamma radiation (3 Gy) on condition of
      proteolytic and antioxidative blood plasma systems of rats have been
      investigated. There are were increase of total proteolytic activity (TPA) on 3
      day, adaptive increase of alpha-antiproteinase inhibitor (API) on 7- and 14-day
      after factors separate action and tendency to increase TPA together with the
      invariable content of API after combine influence. The decrease of alpha-2
      macroglobulin level on 14-day after all influences and more significantly after
      combination of factors action have been also shown. The decrease of antioxidant
      system and system of free radicals inactivation have been observed.

PMID- 9244516
TI  - [The effect of small radiation doses on biological changes in population
      groupings of murine rodents].
AB  - The influence of low doses of radiation on the biological changes in the
      population groupings of rodents is traced. Correlative dependence between the
      factors of accumulation of 137Cs by animals in contact with the forest litter and
      vital functions: intensity of reproduction, death of young animals (Sad) and size
      was found at the example of Clethrionomys glareolus Schreb. However, it is
      necessary to make amendments to the age structure of the grouping under analysis
      to use the mentioned above tests, as young animals accumulate nuclides in
      organism 375 or more times less than grown up ones. The factor of accumulation of
      radionuclides less than 1 can be accepted as the test of radiation-ecological
      well-being of the forest territory and this test can be used in radioecology.

PMID- 9244517
TI  - [The characteristics of DNA repair in the neurons of the rat cerebral cortex
      after gamma irradiation at low doses].
AB  - External gamma irradiation of rats under 0.1-5 Gy causes nonreversible decreasing
      of DNA synthesis in brain cortices neurones in fare later (30 days after
      irradiation). The relative points number of excision initiation, which were
      calculated with the method of BrdU photolysis are much more than under normal
      condition and than just after irradiation also.

PMID- 9244518
TI  - [The effect of small doses of gamma irradiation on the relative content of H1 and
      H1(0) histones in the nuclei of the neurons in the rat cerebral cortex].
AB  - External gamma irradiation of rats under 0.1-2 Gy causes decreasing of histone
      H1(0) contents on the first two days after irradiation and increasing in fare
      later in brain cortices neurones. These changes are observed in fraction of
      chromatin, which has high sensitivity to DNA digestion.

PMID- 9244519
TI  - [The dependence of the biological effect of electron radiation on the pulse
      repetition rate. The dependence of mortality and life span in rats on the
      radiation dose and pulse repetition rate].
AB  - Quantitative regularities have been established for mortality and life-span of
      rats in relation to the pulse recurrence frequency (3-2400 s-1) of electron
      radiation with electron energies of 25 and 50 MeV. Electrons with pulse
      recurrence frequencies of 600 and 1200 s-1 have shown a higher biological
      effectiveness.

PMID- 9244520
TI  - [The dependence of the biological effect of electron radiation on the pulse
      repetition rate. The characteristics of the clinical manifestations in rats after
      irradiation at superlethal doses].
AB  - A comparison between biological effects of electron radiation (25 and 50 MeV) at
      doses of 100-300 Gy and with pulse recurrence frequencies from 3 to 2400 s-1,
      using general damage severity, distinctiveness of separate clinical
      manifestations and incidence of extremely severe forms of radiation sickness as
      criteria, has demonstrated some peculiarities of radiation pathology in rats
      under these circumstances. The pulse recurrence frequency influence varies with
      the criterion applied.

PMID- 9244521
TI  - [The mechanism of the occurrence of vomiting during the primary reaction after
      exposure of the body to ionizing radiations at large doses].
AB  - In the experiments of dogs exposed to ionizing radiations at doses of 50 and 70
      Gy, an essential role of the central mechanism in the origin of early
      postradiation vomiting has been confirmed. Insufficient efficiency of
      dimethpramide, a dophamynolytics, in this case may be connected either with
      initiation of other (non-dophamynosensitive) structures of the chemoreceptor
      trigger zone of with a growing role of the reflex way of vomiting arising due to
      a considerable intestinal injury that causes diarrhea. The inhibition of
      intestinal M-cholinoreceptors by methacine prevented diarrhea but didn't change
      the intensity of the vomiting reaction which, however, does not eliminate the
      possibility of afferentation from receptors that respond to others biologically
      active substances.

PMID- 9244522
TI  - [Calculation of the effective dose in human external irradiation with photons and
      neutrons].
AB  - The method of calculation of the effective dose equivalent for external neutron
      and photon radiation are presented. Adjoint transport Monte-Carlo code ROBOT is
      used to calculate fluence-to-effective dose conversion function for MIRD
      phantoms. Two broad neutron and photon beam irradiations were chosen frontally
      and isotropically. The effective dose conversion functions are presented and good
      agreement is shown with Monte-Carlo calculation by other authors. The received
      data can be used in a new rates of radiation safety.

PMID- 9244523
TI  - [Vitamin metabolism in rats in the early period after a single whole-body gamma
      irradiation].
AB  - A single whole-body gamma irradiation (4 Gy) of rats with the initial deficiency
      in vitamins B1 and B2 had no effect on the contents of vitamins C, A, and B1 in
      the blood plasma, liver, or testicles within 42 h after irradiation. The content
      of vitamin E remained unchanged in the blood plasma but increased in testicles.
      The contents of vitamin B2 remained unchanged in erythrocytes and liver,
      decreased in testicles, and its excretion with urine increased more than twice.
      The content of reduced glutathione in liver, small intestine mucosa, and
      erythrocytes decreased.

PMID- 9244524
TI  - [The activity of the lipid peroxidation processes in the mucosa of the rat small
      intestine and its morphofunctional state under acute irradiation and the
      administration of combined preparations created on a base of highly dispersed
      silica].
AB  - Morphofunctional and biochemical studies were carried out on bastard male rats
      (weight 200-240 g). The results showed that X-ray irradiation had induced
      structural alterations and elevation of lipid peroxidation in small intestine.
      Using of complex preparations defended this organ against pathological damages.
      The first preparation provided rat organisms with 100 ml/kg of silica, 2 mg/kg of
      beta-carotene, 30 mg/kg of alpha-tocopherol and 0.2 mg/kg of natrium selenite.
      The second preparation provided 100 mg/kg of silica, 10 mg/kg of dry Rhodiola
      extract, 0.1 mg/kg of tincture of Lagochilus [correction of Ladohilli] inebrians
      and 0.05 ml/kg of tincture of Aralia mandshurica. The third preparation provided
      organism with 100 mg/kg of silica and 20 mg/kg of thiobenzimidazole derivative.
      All these preparations had produced marked pharmacological effect.

PMID- 9244525
TI  - [The action of sublethal doses of ionizing radiation on the endogenous
      radioresistance background].
AB  - Sublethal doses of X radiation (0.5 Gy and 1 Gy) caused the alterations in levels
      of main components of endogenous radioresistance background in rat tissues. There
      were demonstrated the decrease of serotonin content in stomach mucosa and spleen,
      adrenalin, noradrenalin and corticosteroid contents in adrenal glands, nonprotein
      thiols content in spleen, and the increase of lipid peroxide level in serum on
      the 3-14 days after irradiation. The recovery of the investigated parameters was
      occurred to the 21 day after exposure.

PMID- 9244526
TI  - [Corticosterone and testosterone in the blood of adult rats: the effects of low
      doses and the times of the action of ionizing radiation during intrauterine
      development].
AB  - Corticosterone levels in the blood and adrenal weights in adult rat males were
      increased after low-dose gamma irradiation during the last third of their
      intrauterine development; an increase of the dose decreased them. Decrease in
      testosterone levels and testis weights were dose-dependent. External and internal
      irradiation of females on the 11-14 days of pregnancy inhibited adrenals and
      increased testosterone levels and seminal vesicles weights in offspring. The
      changes of hormonal balance in adult animals depend on dose and period of
      ionizing irradiation during intrauterine development.

PMID- 9244527
TI  - [The effect of superhigh doses of gamma radiation on the energetics of rat liver
      mitochondria].
AB  - The effect of high dose of gamma radiation (200 Gy) on energy of rat liver
      mitochondria was studied. 1 hour after irradiation state 3 (V3) increased by 32
      +/- 7%, state 4 (V4)- by 25 +/- 8%, the rate of ATP synthesis by 52 +/- 11%. 48
      hours after irradiation these parameters decreased to control levels inspite of
      accumulation of lipid peroxidation products.

PMID- 9244528
TI  - [The combined effect of ionizing radiation and benzene on immunoreactivity
      indices in the spleen and lymph nodes].
AB  - Under the influence of the combined action of gamma irradiation (1 Gy, 1,15
      Gy/min) and benzene the synergistic reduction of proportion and absolute content
      of B-cells and less expressed reduction of absolute content T-cells in spleen and
      lymph nodes was observed. In spleen the thymus-dependent humoral immune response
      was resistant to combined effect of irradiation and benzene, while in lymph nodes
      it was highly sensitive. The profound suppression of antibody formation in lymph
      nodes was characterized by synergism. It was accompanied by the block of specific
      recruitment of antigen sensitive cells within drained lymph nodes from migrating
      stream. The suppression of local immune response resulting from the combined
      effect of radiation and toxicants may be the cause of protective immunity
      disturbance.

PMID- 9244529
TI  - [Mast cell reaction to total irradiation].
AB  - A morphofunctional changes of peritoneal and mesenteric mast cell populations in
      rats from first minutes up to 10 day after irradiation in dose 5.5 Gr were
      studied. It is shown that the increased mast cell degranulation is of the first
      reactions of organism on irradiation. Mast cell reaction on irradiation is
      biphasic; the quick, short first phase is observed approximately during 0.5 h
      after irradiation, the gradual prolonged second phase reaches its peak about 5-12
      h and continues at least during 10 days.

PMID- 9244530
TI  - [A comparative study of the immunological (antimicrosomal antibodies) and
      cytogenetic indices of children living in radioactively contaminated areas of
      Bryansk Province].
AB  - The chromosome dicentric aberrations in the lymphocytes and levels of antibodies
      to human thyroid microsomal antigen in the serum of the children lived in the
      area of Bryansk Province suffered from the Chernobyl accident was examined.
      Correlation between those tests was not estimated: the autoantibodies were
      revealed in group with dicentrics and without those in 4.0% and 4.5% of cases
      correspondingly. Antimicrosomal antibodies were revealed more frequently (5.0%)
      and in higher titers in the children from the more polluted Bryansk Province than
      in those from Kaluga Province (3.1%). These data can testify about the role of
      inside radiation of thyroid gland in appearance of autoimmune thyroiditis signs.

PMID- 9244531
TI  - [The patterns of the mutagenic action of radiations with different LETs on
      Bacillus subtilis cells].
AB  - The induction of the his(-)-->his+ mutants in vegetative and spores of Bacillus
      subtilis wild-type cells irradiated with gamma rays and helium ions (LET = 20-80
      keV/micron) has been investigated. It was shown that the dose dependence of the
      mutation induction in vegetative cells is described by a linear-quadratic
      function of dose in case of both gamma-rays and helium ions. RBE (LET)
      dependencies on the lethal and mutagenic effect of irradiation have a local
      maximum. The maximum of RBE (LET) dependence on the mutagenic assay is shifted at
      the low region of LET in comparison with the lethal effect of irradiation.

PMID- 9244532
TI  - [Quantitative patterns in the clinical manifestations of radiation sickness in
      large laboratory animals exposed to radiation at superlethal doses. The
      quantitative patterns in the manifestations of radiation sickness in monkeys].
AB  - Radiation sickness manifestations have been studied in two species (Macaca
      fascicularis and Papio hamadryas) exposed to electron and gamma-neutron
      radiations in a wide supralethal doses range. Dose-response relationships have
      been calculated for mortality and some clinical manifestations of the intestinal
      and cerebral forms of radiation sickness. Higher radiosensitivity of baboons in
      comparison with Macaca fascicularis and clinically more dangerous damage due to
      electrons as compared to gamma-neutron radiation have been demonstrated.

PMID- 9244533
TI  - [Quantitative patterns in the clinical manifestations of radiation sickness in
      large laboratory animals exposed to radiation at superlethal doses. The
      quantitative patterns in the manifestations of radiation sickness in dogs].
AB  - Radiation sickness manifestations have been studied in dogs exposed to electrons
      (electron energy 25 MeV) and gamma-neutron radiation (neutron energies of 0.37
      and 1.2 MeV) in a wide dose range. Dose-response relationships have been
      calculated for mortality and some clinical manifestations of the intestinal and
      cerebral forms of radiation sickness. With regard to mortality, the highest
      effect has been observed for gamma-neutron radiation with a neutron energy of 1.2
      MeV. For equal physical doses and for those equally effective in relation to
      mortality, clinical manifestations of damage are more prominent following
      exposure to electrons.

PMID- 9244534
TI  - [Quantitative patterns in the clinical manifestations of radiation sickness in
      large laboratory animals exposed to radiation at superlethal doses. Changes in
      the regulation of cardiovascular system function].
AB  - Dog exposure to doses from 39 to 124 Gy results in an increase of heart rate and
      tension in control of the cardiac rhythm, the extent being dose dependent. An
      additional physical load on the cardiovascular animals system reveals a high
      functional control reserves of the cardiovascular system which provides stable
      functioning even after exposure to the above doses.

PMID- 9244535
TI  - [The variability of the biochemical status of populations of the bank vole
      (Clethrionomys glareolus) subjected to the chronic action of ionizing radiation
      in relation to the time of their inhabiting radionuclide-contaminated areas].
AB  - The existence of a population of bank voles in the course of long time (50-60
      years) in conditions of chronic ionizing radiation at low doses, promoted
      adaptation of this populations of rodents to the action of this factor. As
      opposed to, in a population of bank voles, living radionuclide-contaminated areas
      during 8-years after the Chernobyl accident, adaptation was not observed.

PMID- 9244536
TI  - [The build up of absorbed doses in the critical organs of cereal grains in a
      contaminated area after the accident at the Chernobyl Atomic Electric Power
      Station].
AB  - The calculation method for absorbed doses of ionizing radiations in critical
      organs of cereals during the first vegetation period after the ChNPP accident is
      presented. Calculation of radiation burden on plants nearly 5 settlements in the
      30 km zone of ChNPP accident are carried out. gamma-radiation of radionuclide
      fallouts is demonstrated to give the main contribution into absorbed dose and
      dose ratio beta- to gamma-radiation varied within the range from 5 to 10
      depending on radionuclide composition of fallouts.

PMID- 9244537
TI  - [Active forms of oxygen and the degree of UV modification of the structural and
      functional properties of lactate dehydrogenase].
AB  - The spectrophotometry and photofluorescence techniques were used in the studies
      on photochemical transformations of lactate dehydrogenase exposed to UV
      irradiation with a dose of 2.25 kJ/m2, in the native state and in the presence of
      exogenous modifiers: sodium azide, beta-carotene, histidine, D-mannitol, and tret
      butanol. It was shown that UV irradiation of the mixtures of lactate
      dehydrogenase with sodium azide, beta-carotene, and histidine results in
      restoration (by 99, 65, and 63%, respectively) of the level of catalytic activity
      of the enzyme as compared to that observed after irradiating it in the absence of
      the protectors. The protective effect provided by mannitol during UV irradiation
      of the lactate dehydrogenase was 23%. Thus, it was shown that active oxygen
      species--singlet molecular oxygen and hydroxyl radical--make significant
      contributions to photomodification of lactate dehydrogenase.

PMID- 9244538
TI  - [The structural typology of the human cerebral cranium].
AB  - 819 skulls (250 of them were represented as frontal sections) obtained from men
      and women of different age were examined in order to study the variability of
      human cerebral cranium biomechanical stability to external mechanical influences
      and to work out its morphological constructional typology. Methods were based
      considering cerebral cranium as a coat, approximating to half of the rotation
      ellipsoid in shape. The following craniotypes are the extreme types of cerebral
      cranium construction stability, a) morphologically-stable one, where strength is
      provided both by great bone thickness and small curvature radiuses, 6)
      structurally-stable, in which strength is provided by great bone thickness, B)
      configurationally stable in which strength is provided by curvature small
      radiuses, r) morphologically unstable with small bone thickness and great
      curvature radiuses. Phylo-ontogenetic dynamics of human cerebral cranium
      construction stability was followed up.

PMID- 9244539
TI  - [Age-related changes in the goniometric indices of the pelvic bones in children].
AB  - The present research was aimed to study changes of angular parameters of pelvic
      bones in children depending on age and sex. The following are angular parameters
      studied: 1) pubic arch angle; 2) ischiadic angle; 3) angle of pubic bone rami
      inclination; 4) angle of anterior pelvic semicircle; 5) angle of symphysis
      inclination; 6) angle of pelvic inclination. To assess the results obtained and
      reveal variability regularities variation-statistical processing was performed.

PMID- 9244540
TI  - [Topographic anatomy of the lungs in computed imaging].

PMID- 9244541
TI  - [Do we know everything about the coronary arteries of the heart?].

PMID- 9244542
TI  - [The role of oxytocin and vasopressin in the regulation of mammalian
      reproduction].
AB  - Nonapeptides, oxytocin and vasopressin are known to be involved in the
      realization of mammalian reproduction. Nonapeptides are synthetized in
      neuroendocrine and neuronal brain structures as well as in peripheral tissues,
      including gonads. The aim of the present review is the analysis of recent
      literary and authors own data on sexual dimorphism in the nonapeptidergic
      hypothalamo-hypophysial system, interaction between this system and hypothalamo
      pituitary-gonadal axis, the role of nonapeptides in sexual behaviour as well as
      autocrine production of oxytocin and vasopressin in the testis. The special
      reference in the review is given to the nonapeptide gene expression in the brain
      and testis.

PMID- 9244543
TI  - [The structure of pseudocystic formations in the temporal lobe in focal
      epilepsy].
AB  - The material obtained in open operative interventions from 117 patients with
      focal (temporal) epilepsy was studied. In 58% of the observations rounded and
      oval-shaped cavities with distinct borders without any lining, i.e. pseudocystic
      structures were found. By morphological traits they could be related to cribllurs
      as there is a vessel in each cavity. All-level disturbance of intracerebral
      vessels and damage of blood-brain barrier together with hypoxia associated with
      it are probably the reason for criblir development. Pseudocystic structures that
      are not connected with the vessel lesion could be of another, sometimes
      inflammatory genesis. Thus, pseudocystic structures that unite in a network of
      channels connected with subarachnoidal space occur in temporal lobe in focal
      epilepsy in over half of cases.

PMID- 9244544
TI  - [Age-related changes in the cytoarchitectonics of the human sensorimotor cortex].
AB  - The study of human brain sensomotor cortex architectonics within the period since
      birth up to 20 years with a year long intervals demonstrated that pyramidal
      neurons differentiation is most intensive in area 4p throughout the period since
      birth up to 6 months, in area 6p--up to one year and in area 6op--up to 2 years.
      Pyramidal neurons proportion in sublayer 3 increases significantly in all
      sensomotor cortex areas within the first postnatal year and its growth continues
      up to 15-16 years. In area 5 proportion of pyramidal neurons in areas studied
      undergoes the period of intensive growth up to one year, than it starts to
      increase by 6-7 years, and finishes its growth in areas 6 and 6op by 14 years and
      in area 4p--by 16 years.

PMID- 9244545
TI  - [The differentiation of locus coeruleus neurons after their allotransplantation
      into the preliminarily denervated hippocampus of white rats].
AB  - The suspension of embryonic locus coeruleus (LC) was transplanted into outbred
      albino rat hippocampus after its preliminary 6-hydroxy-dopamine-induced
      denervation. Immunohistochemical and morphometric analysis revealed that 3 months
      after the transplantation, embryonic noradrenergic LC cells which have completed
      their histogenesis in recipient hippocampus, appear as differentiated multipolar
      and fusiform cells, typical to LC. Intrahippocampal allotransplants of rat
      embryonic LC were also demonstrated to normalize the level of orientation
      activity in an open area, that was significantly reduced after administration of
      6-hydroxy-dopamine to the animals.

PMID- 9244546
TI  - [Cytochrome oxidase distribution in the normal cat midbrain and after unilateral
      enucleation (a histochemical study)].
AB  - Histochemical method of cytochrome oxidase demonstration was used to study its
      distribution in frontal sections of tectum of the midbrain in cat in normal
      conditions and after unilateral enucleation. Basic layers of this formation were
      demonstrated in normal conditions similar to those revealed using classical
      histological methods. After unilateral enucleation rostral, middle and caudal
      parts of superior colliculus were stained differently. Contra- and ipsilateral
      surface layers in rostral and caudal parts were stained also with different
      intensity. Alteration of lightly and intensely stained patches appeared in middle
      part. Peculiarities of staining in cytochemical cytochrome oxidase demonstration
      in superior colliculus of tectum of the midbrain in enucleated animals are likely
      to reflect peculiarities of this structure afferentially by retinotectal,
      geniculotectal and geniculocortical fibres.

PMID- 9244547
TI  - [Changes in the oxytocinergic neurosecretory cells in the accessory magnocellular
      neuroendocrine nuclei of the rat hypothalamus during aging].
AB  - Histophysiology of accessory magnocellular nuclei of hypothalamus was studied in
      young (3-6 months) and old (14-29 months) male Wistar rats. Using non-labeled
      antibodies to oxytocin and karyolometry activation of protein synthesis combined
      with inhibition of oxytocin transport along the fibres was shown to occur in 4
      (circular, fornical, dorso- and ventrolateral) of 5 accessory nuclei in old rats.
      This was not observed in anterior commissural nucleus. A hypothesis on
      compensatory role of accessory magnocellular nuclei of hypothalamus in regulation
      of neuroendocrine homeostasis in old rats is discussed.

PMID- 9244548
TI  - [The formation of psammoma bodies in the choroid plexus of the human brain].
AB  - Formation of psammoma bodies (PB) in choroid plexus of human telencephalon was
      studied using histochemical and immunocytochemical methods. PB formation was
      found to start during childhood. In early stages of development PB are not
      calcified and are formed by fibroblasts possessing a series of cytological
      diversities from the fibroblasts of the surrounding connective tissue. Cytoplasm
      of PB forming fibroblasts contains greater amount of vimentin. A suggestion is
      made on existence of special population of fibroblasts with an ability to form PB
      in connective tissue.

PMID- 9244549
TI  - [The structural organization of arterial branchings].
AB  - The study presents the results of examination of arterial ramifications of some
      organs in man and laboratory animals. Musculoelastic sphincters (MES) were found
      in orifices of different caliber arteries using a complex of histological,
      histoenzymochemical and experimental methods. Three types of these structures
      were distinguished. It was shown that in disorders of blood circulation in
      patients with congenital heart diseases and in dogs with models of the defect the
      extent of sphincter apparatus increases. MES role is limited to regulation of
      regional hemodynamics and maintenance the adequacy between organ blood influx and
      the level of their functioning.

PMID- 9244550
TI  - [The development of the thoracic duct lymphangions in the prenatal period of
      human ontogeny].
AB  - The study was performed in 77 fetuses and 10 cadavers of newborns using the
      complex of methods, the basic one being the total preparation after A. V.
      Borisov. Thoracic duct lymphangions develop craniocaudad in 13-18 week fetuses.
      Maximal number of intervalvular segments (up to 35) was observed during the
      middle of intrauterine development. They achieve definitive number (15-20) by the
      moment of birth which correlates with active formation of muscular base. The wall
      of duct in fetus has constructions of capillary, postcapillary, non-muscular and
      muscular type vessel. Lymphangion is primitive in 13-28 week fetuses and
      definitive in 29-36 week ones. Local peculiarities of lymphangion
      myoarchitectonics were shown. The role of accessory beds of the duct in lymph
      passage was demonstrated.

PMID- 9244551
TI  - [Structural changes in the tissues of white rats after capsaicin administration].
AB  - Tissue structure of albino rat lung, skin and cornea changing after
      administration of capsaicin (neurotoxin isolated from red pepper) was studied
      using light and electron microscope. 5 mg/kg dose causes tissue swelling and
      microcirculatory bed reaction. 200 mg/kg dose leads to more significant
      dystrophic tissue alterations. Fibrosclerosis signs were found in certain cases.
      Microcirculatory disorders are proposed as the main reason for tissue structure
      alterations observed, although the mechanism of their development is still
      unclear.

PMID- 9244552
TI  - [The normal ultrastructure of the erythrocytes and in experimental portal
      hypertension].
AB  - Erythrocyte types were studied in portal and femoral veins blood in intact dog
      and in the experimental portal hypertension under scanning electron microscope.
      Three basic types (discoid, polygonal and spherocyte) were distinguished.
      Analysis of the material obtained confirmed the suggestion on the existence of
      stable erythrocyte types both in normal conditions and pathology. Content of
      these types in blood of vessels named is different. Inferior caval vein system is
      inaccessible for erythrocytes with significantly altered shape because they are
      unable to penetrate liver sinusoids. In portal hypertension essential increase of
      these erythrocytes number occurs and they are encountered in femoral vein blood.
      These forms obviously pass into the general blood flow through multiple
      collaterals. One of the criteria for portal hypertension diagnostics is suggested
      so as the method of evaluating portal vein shunts in conditions of the formed
      collateral blood stream.

PMID- 9244553
TI  - [The mechanisms of the stimulating effect of tissue basophils on the reparative
      processes in inflammation].
AB  - Mast cells stimulating effect on reparative processes in inflammation involves
      histamine, serotonin and heparin. This was shown on the model of E. coli-induced
      acute infectious peritonitis in rats using antagonists of major biologically
      active mast cells products (histamine, serotonin and heparin)-dimedrole,
      cimetidine, ciproheptadine and protamine sulfate. Fibroblast accumulation is
      associated with histamine, influencing predominantly H1- and H2-receptors as well
      as with serotonin. Fibroblast proliferative synthetic ability increases through
      histamine action on H1-receptors and serotonin and heparin influence.
      Accumulation of monocytes-macrophages and their proliferative synthetic ability
      stimulation is affected by histamine (through H1-receptors) and serotonin.

PMID- 9244554
TI  - [The functional morphology of the Langerhans cells in the female reproductive
      tract].
AB  - The modern views on the distribution, morphological and functional
      characteristics of Langerhans cells (LCs) and their role in the immunological
      defense system in female genital tract are summarised. Within this tract, LCs are
      situated mainly in the mucosal epithelia of vagina and uterine cervix. They are
      surrounded by hormone-dependent and cyclically changing epithelium and are highly
      sensitive to hormonal and deleterious factors. LCs function as a component of
      afferent limb of the local immune system. which has special properties as it is
      modulated by the changing hormonal levels, provides the antimicrobial immunity
      and is tolerant to multiple immunization with sperm antigens. Perspectives in the
      study of LCs in female genital tract are discussed.

PMID- 9244555
TI  - [The vascularization of skin connective-tissue regenerates during wound healing
      under exposure to neurotransmitters and their antagonists].
AB  - Vascularization of skin regenerates was studied in wound healing as affected by
      noradrenaline (NA), acetylcholine (Ach), propranolole (PR) and atropine (AT).
      Regenerate vascularization was reduced under NA and AT effect, while Ach and PR
      promote its increase. Deviation extent of values of granulation tissue vessels
      specific length (SLV) (by 7th posttraumatic day) increases in proportion with the
      drug dose. Schematic diagrams of the studied "dose-effect" correlation
      approximate to S-like (logistic) curve. Relative change of SLV in regenerating
      dermis, that occurs as a response to wound treatment with NA, Ach, PR and AT, non
      significantly expressed by third experimental day, grows sharply by day 7 and
      then reduces gradually. SLV reactive deviation in cholinotropic preparation use
      exceeds that after treatment with adrenotropic ones. Skin regenerate vessels
      reactions to neurotransmitters and their antagonists are not only quantitative,
      but qualitative as well.

PMID- 9244556
TI  - [The structure of the connective-tissue framework of the skin regenerate in rats
      during the trypsin and ronidase stimulation of wound healing].
AB  - Peculiarities of formation of connective tissue framework of granulation tissue
      and scar were studied using light optical and scanning electron microscopy in
      rats during all-layer skin wound healing in interscapular region. Formation of
      granulation tissue and scar was accelerated after daily 20 minutes treatment with
      0.2% trypsin and 0.1% ronidase solutions as compared to that in control.
      Regenerates are characterized by different morphological properties. Trypsin
      promotes quick formation of collagen fibre fascicles with their following
      thickening and gradual exfoliation. Ronidase action leads to small diameter
      collagen fibres formation and their following organization into larger fascicles.
      The peculiarities established are associated with different mechanisms of enzyme
      effect on reparative processes.

PMID- 9244557
TI  - [Morphological changes in the adrenal gland during adaptation to multiple
      individually measured physical loads].
AB  - Morphological equivalents of adrenals response of their high efficiency were
      studied in individually dosed movement loads using a complex of morphological,
      physiological and biochemical methods. Two types of reaction were demonstrated
      after individual analysis. In animals with minimal growth of efficacy low
      concentrations of cortisol in serum are followed by significant activation of all
      the cortical elements in low functional activity of adrenal medulla. High
      efficiency of adrenals work is accompanied with moderate activity of adrenal
      cortex and medulla combined with high concentrations of cortisol.

PMID- 9244558
TI  - [Structural changes in the liver of dogs under physical training at high
      altitude].
AB  - Physical training in mountains leads to significant structural disorders in dog
      liver. In early stages (up to 15 days of staying in mountains) dystrophic
      processes prevail in trained animals liver, while in later ones (on day 30),
      repair processes take over, although destruction traits are still retained.

PMID- 9244559
TI  - [Intercalated (basal) epitheliocytes and the regeneration of cholangiocytic
      epithelium in the liver].
AB  - Certain authors controversial view on intercalated (basal) cambial cells
      existence in enterodermal epithelia is substantiated by complex study of cells in
      cholangiocyte lining of interlobular bile ductules (hepatic ductules).
      Comprehensive explanation of mechanisms of ductules growth on cholestasis is
      obtained, taking into account the data concerning basal and other types of
      cholangiocytes.

PMID- 9244560
TI  - [The morphofunctional basis for the effect of respiratory movements on urine
      production and the urinary excretory functions of the kidneys in the turtle].
AB  - Influence of respiratory movements on urine formation and excretory function of
      turtle kidneys are substantiated in the present research. It was performed in 55
      mature male steppe turtles using injection, histological, histochemical and
      experimental methods. Following animal transfer to regulated respiration by means
      of tracheostome application the oscillations of tension were monitored in ureter
      lumen and cavities surrounding kidney as well as change in shape and size of
      initial widened regions of excretory tubules as a response to strong inspiration
      and expiration. These structures were shown to affect uric acid and mucin
      secretion and urine passage in ureter tributaries and ureters.

PMID- 9244561
TI  - [A mathematical analysis of the structure of the elements in the human
      maxillodental apparatus].
AB  - On the example of "Golden wourf" and some other models the use of mathematical
      methods in stomatological morphometry is demonstrated. Parameter values
      oscillations below 15% are considered by the authors to be the limit for normal
      state individual peculiarities. Relief of dental crowns are considered from
      biomechanical positions, representing dentition localisation as parts of conic
      surfaces.

PMID- 9244563
TI  - [Health education in Lebanon: current state and perspectives].

PMID- 9244562
TI  - Timing and genetic regulation of commitment to sporulation in Bacillus subtilis.
AB  - Sporulation in Bacillus subtilis is a simple developmental system involving the
      differentiation of two cell types called the prespore and the mother cell. The
      process is induced by nutrient deprivation and culminates with the formation of a
      mature spore, which is released by lysis of the mother cell. We have studied
      commitment to sporulation with several different assays. The results indicate
      that commitment occurs soon after the formation of the asymmetrically positioned
      division septum that separates the prespore and the mother cell. This is earlier
      than the previously postulated point of commitment, prespore engulfment by the
      mother cell. Commitment coincides approximately with activation of the early
      prespore- and mother-cell-specific sigma factors, sigma(E) and sigma(F).

PMID- 9244564
TI  - [Substances affecting the synthesis and activity of leukotrienes].
AB  - Leukotrienes play an important role in inflammation and asthma. This paper
      briefly deals with compounds influencing leukotriene biosynthesis and activity. 5
      Lipoxygenase inhibitors (e.g., zileuton) and FLAP inhibitors (e.g., quiflapon)
      hinder biosynthesis of all leukotrienes. LTB4 production may be limited by LTA4
      hydrolase inhibitors. Attention is also paid to leukotriene receptor antagonists.
      LTB4 antagonists (e.g., SC-51146) should be useful in the treatment of diseases
      in which a prominent neutrophil infiltrate is present, especially psoriasis and
      inflammatory bowel disease. Peptidoleukotriene (LTC4, LTD4, LTE4) antagonists,
      such as zafirlukast and pranlukast, are currently being developed as
      antiasthmatics.

PMID- 9244565
TI  - [Prunella vulgaris L.--a rediscovered medicinal plant].
AB  - In the past, the self-heal (Prunella vulgaris L.) was primarily used as a remedy
      alleviating pains in the throat, fevers and accelerating wound healing. A high
      content of rosmarinic acid, immunomodulation effects of the polysaccharide
      prunelline and antiviral activity of some constituents make the plant interesting
      from the viewpoint of therapeutical applications. The paper summarizes the
      contemporary phytochemical knowledge about the self-heal and the results of
      pharmacological studies of the extracts and pure substances from this plant.

PMID- 9244566
TI  - [A modeling analysis of possible generic substitutions in an inpatient facility].
AB  - The paper presents an example of a sectional analysis of drug consumption in a
      large in-patient health-service facility which is to be used as a foundation for
      making decisions about the measures to decrease the costs of drugs. Consumption
      of industrially produced pharmaceutical preparations at a selected facility for a
      period of four months was analyzed. The authors evaluated possible substitution
      of administered important preparations by cheaper equivalents and by means of
      model analysis they calculated expected savings when using the cheapest available
      mass-produced pharmaceutical preparations. In the preparations under study,
      possible savings of costs in the extent of 2.2% of the spent sum were found. On
      the basis of the results of the analysis, the hospital formulary authors consider
      the positive list with a quality system of objective monitoring of drug
      consumption to be the most suitable way of introduction of more rational
      prescription of industrially produced drugs in an in-patient facility.

PMID- 9244567
TI  - [HPLC analysis of non-steroidal antirheumatic agents in biological material. II.
      Profens].
AB  - The present paper surveys the published HPLC methods evaluating profens in
      biological materials and reports a HPLC method for the determination of ibuprofen
      in the samples of whole blood. For liquid-liquid extraction, ibuprofen was
      analyzed on the reverse phases Separon SGX C18 with the mobile phase methanol
      water (pH 3.0) and detected at 222 nm. The elaborated method was employed in a
      pharmacokinetic study of ibuprofen on laboratory rabbits.

PMID- 9244568
TI  - [RP-HPLC retention characteristics of benzodiazepines during ion-pair
      chromatography].
AB  - The paper studies retention parameters of the therapeutically most frequently
      used benzodiazepines, i.e. diazepam, oxazepam, medazepam, chlorodiazepoxide, and
      nitrazepam. The effect of the pH of the mobile phase, percentual representation
      of methanol, character of the used buffer and the addition of hexanesulfonic acid
      on the retention time, shape and symmetry of the peaks of the drugs under study
      were examined. The analysis was carried out on a column filled with Separon SGX C
      18. The best results were achieved using the mobile phase methanol-phosphate
      buffer 0.05 mol/l pH 3.00 65:35, detection with a UV detector at a wavelength of
      250 nm. The optimized chromatographic conditions were applied to the analysis of
      benzodiazepines in rabbit plasma samples.

PMID- 9244569
TI  - [Anti-inflammatory activity of aqua-bis(2,Y-diacetoxybenzoate)-copper complexes
      (Y=4, 5 or 6)].
AB  - In a group of binuclear copper (II) complexes of the composition
      [Cu2(RCOO)4(H2O)2] (R = 2,4-diacetoxyphenyl (I), 2,5-diacetoxyphenyl (II) and 2,6
      diacetoxyphenyl (III)), the anti-inflammatory activity was assayed in rat paw
      carrageenan-induced edema. Copper (II) salicylate tetrahydrate (IV) and salicylic
      acid were used as standards for comparison. All compounds were applied i.p. in a
      single dose of 50 mumol/kg body weight, calculated for the R-COO-fragment. The
      Cu(II) complexes tested were clearly more effective than the corresponding free
      diacetoxybenzoic acids, with an exception for the 2,5-diacetoxy derivative. The
      average anti-inflammatory activities of copper (II) complexes were decreasing in
      the following order: III (71.0%) = (70.6%) > IV (57.4%) > II (18.0%). Of the
      acids, only 2,6-diacetoxybenzoic acid (45.2%) was effective at the level of
      salicylic acid (44.9%). The relationship between the coordination-chemical
      properties and the biological effects of the complexes tested is discussed.

PMID- 9244570
TI  - JASTS XXX. 30th Japanese Symposium on Taste and Smell. Osaka, Japan, October 29
      31, 1996. Abstracts.

PMID- 9244571
TI  - Congress of Molecular Medicine. Berlin, May 3-5, 1997. Abstracts.

PMID- 9244572
TI  - [Eulogy of Robert Laplane (1907-1996)].

PMID- 9244573
TI  - [Calicivirus infection of the hare and human calicivirus].
AB  - The calicivirus outbreak in hares which occurred in Center West of France in the
      fall of 1996 illustrates the pathogenic role of caliciviruses in animals and in
      humans. A comparison of these different viruses, based on the RNA nucleic
      sequences is presented. The aspect of interspecies transmission is also
      discussed.

PMID- 9244574
TI  - [Influenza: interspecies transmissions and viral rearrangement].
AB  - Influenza is an infection of humans beings and many animal species. It is caused
      by viruses which belong to the Orthomyxoviridae family. There are three types of
      influenza viruses A, B and C. The type A is the most pathogenic of all. The type
      is determined mainly by the nature of the nucleoprotein (NP), an antigen which
      does not greatly vary. On the contrary, the surface antigens, among which the
      haemagglutinin is the most important, are highly variable and their nature
      determines the sub-type of virus within the type A. The expressed mutations
      affecting the haemagglutinin are referred as antigenic drift and make virological
      surveillance necessary in order to annually assess the composition of the vaccine
      strains. The segmented nature of the genome of influenza viruses, makes possible
      the genetic reassortment of two different influenza viruses co-infecting one cell
      and produces a new hybrid virus. When such an event affects the haemagglutinin,
      the reassortment leads to an antigenic shift. In nature, it most certainly takes
      place in swine, between human and avian viruses. Whereas antigenic drift is a
      continuous and progressive phenomenon, antigenic shift occurs occasionally every
      10 to 30 years. The emergence of a hybrid virus bearing a new haemagglutinin and
      thus belonging to a new human subtype, can be the starting point of the genesis
      of a pandemic, generally associated with a high mortality rate in humans. The
      participation of the pig is specially mentioned.

PMID- 9244576
TI  - [Thematic meeting: "Urban atmospheric pollution and public health"].

PMID- 9244575
TI  - [Helicobacter infections of man and of domestic carnivores: comparative data].
AB  - The role of Helicobacter pylori in generating of the chronic gastritis and in the
      maintaining of the gastroduodenal ulcerous disease, has been a major medical
      discovery of these past years in human gastroenterology. More recently in Man,
      studies have showed that the gastric tumours (adenocarcinoma, lymphoma) are
      epidemiologically associated with the H. pylori infection. Although the H. pylori
      infection is the one of the most frequent in the word, the epidemiologic and
      ecologic aspects of this infections are still not very well known. Thanks to
      phylogenic studies using the new molecular biology techniques and to fundamental
      experimental studies, we know more about helicobacteria in domestic carnivores as
      well as their morphologic characteristic, their taxonomia and more importantly
      details concerning their ecological niche. Few clinical studies have been made to
      this day, but the ones that have been undertaken are interesting in confirming
      the extensive prevalence of Helicobacter infections in domestic carnivores and in
      underlining their role in the genesis of the inflammatory gastropathies observed
      in these species. Recent observations have demonstrated the ubiquitous character
      of these helicobacteria by showing their presence in the stomach of man, dogs and
      cats. This ubiquitous character has led some scientists to consider the potential
      zoonotic risk of the human infection by Helicobacter heilmannii, felis or pylori.
      Finally, the Helicobacter infection of animals seems to be an interesting model
      not only in the study of the affections caused by these bacteria, but also in the
      elaboration of a future vaccine against the H. pylori infection in man.

PMID- 9244577
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9244578
TI  - [The student family as a social priority in a contemporary society].
AB  - Discusses plans of marriage among students and the problems of student families.
      Comprehensive sociohygienic study of the health status and communal conditions
      was carried out among the students of the Russian Peoples' Friendship University,
      including married students with children. This social group is characterized by a
      peculiar life style, intensive intellectual and social activity; moreover, it is
      the most favorable period for marriage and childbirth. Special attention is paid
      to difficulties (material, communal, educational, etc.) experienced by the female
      students becoming mothers in the course of studies. Specific medicodemographic
      tendencies brought the authors to a conclusion that development and introduction
      of programs of medicosocial support for student families, specifically, mothers,
      is needed, which should be aimed at the soonest possible solution of the acute
      problems of maintaining the health of mothers and their children.

PMID- 9244580
TI  - [The peculiarities of the health of women-mothers who work in the cattle breeding
      sector].
AB  - The paper deals with problems arising in health protection of women engaged in
      cattle breeding and of their children. Analysis of the morbidity in this
      population, based on the analysis of consultation rate and results of profound
      medical examinations showed its level to be high. The authors propose new
      organization measures aimed at health improvement and fortification under
      conditions of a rural health center.

PMID- 9244579
TI  - [The dynamics of the health status of pregnant women and children in the
      framework of the gynecological-therapeutical-pediatric complex].
AB  - A system has been developed for the follow-up of the health status of pregnant
      women and babies, applying an individualized approach to every subject and based
      on the comprehensive sanitization at an obstetrical, therapeutic, and pediatric
      unit, implemented on the general medical practice principle. Such an approach
      helps stabilize the main parameters of the health status of pregnant women,
      newborns, and infants and involve the social centers and territorial social
      protection service in the solution of these tasks.

PMID- 9244581
TI  - [Social-hygienic factors of health status of the population in the North-Eastern
      Russia at the present time].
AB  - Besides the pattern of distribution of the basic extensive characteristics
      reflecting the actual health status of the Chukotka and Magadan district
      population, adequate mathematical models describing the time course of some of
      the examined demographic processes were developed in the course of a
      comprehensive study of the health parameters and demographic structure of the
      population of the North-Eastern Russia. A prediction of the situation up to the
      year 2015 was made, using these models. Ranging of the natural and social factors
      by their influence on the health status and demographic parameters of the Extreme
      North was carried out.

PMID- 9244582
TI  - [Medico-social aspects of sexual and reproductive behavior of young people].
AB  - Discusses the negative aftereffects of sexual and reproductive behavior of modern
      young people. Special attention is paid to medicosocial aspects, such as
      increased incidence of sexually-transmitted diseases, undesired pregnancies,
      induced abortions and deliveries in adolescents. The effect of natural birth on
      the health status and development of a child is demonstrated. A conclusion is
      made on the necessity of more intensive work aimed at preparing young people to
      marriage and childbirth.

PMID- 9244583
TI  - [The aspects of health of forced migrants in the Western Siberia].
AB  - A sociohygienic and medicodemographic characterization of the health status of
      forced migrants (refugees) was made on a model of a large industrial city in West
      Siberia. Morbidity for the most informative disease classes was studied using
      interviews and medical examinations of a random sampling of a representative
      group of refugees aged over 16 years. Each group of refugees from certain regions
      (Kazakhstan, Uzbekistan, Kirghizstan, and Tajikistan) is characterized by
      specific features in the structure of certain disease incidence. Nervous and
      mental disorders are an exclusion: their prevalence is 7 to 14.5 times higher
      than in the local controls in all refugees, except those from Kirghizstan.

PMID- 9244584
TI  - [The problems of the handicapped: medico-statistical aspects].

PMID- 9244585
TI  - [The epidemiology of retinal vein thromboses in hypertensive patients].
AB  - A total of 518 patients aged 35 to 65 with stages I and II essential hypertension
      without clinical signs of utherosclerosis were examined. 3.2% of patients had a
      history of retinal vein thrombosis (RVT). RVT as a complication of essential
      hypertension is most prevalent in men aged 51 to 55 and in women aged 56 to 60.
      This complication was observed only in patients with stage II hypertension, being
      4 times more incident in patients with crises and 9.5 times more frequent in
      subjects who neglected regular antihypotensive treatment. A cooperation of the
      ophthalmologist and therapist is the basic condition of effectively treating
      patients with essential hypertension and a history of RVT, because proper
      treatment of the underlying condition prevents RVT.

PMID- 9244587
TI  - [On the state mechanisms of public health reform].

PMID- 9244586
TI  - [On social-hygienic characteristics of female patients with myocardial
      dystrophy].
AB  - Comprehensive sociohygienic and clinical examinations of women aged 40 to 55
      living in the town of Stavropol was carried out. Climacteric myocardiodystrophy
      was revealed in 12.5% of the examinees. Hence, the incidence of this diseases in
      women aged 40-55 was for the first time reliably calculated for a representative
      sampling. The author presents for the first time information on the share of
      climacteric diseases in women aged 40 to 55, 27% of whom suffer from pathological
      climacteric. The mean age of patients with climacteric myocardiodystrophy is 50.7
      +/- 0.03 years. In addition, the author analyzed the relationship between the
      education and type of labor, work duration, and social status, on the one hand,
      and the incidence of climacteric myocardiodystrophy in the studied sample, on the
      other.

PMID- 9244588
TI  - [The problems of information availability for practising physicians].
AB  - The authors examine the cause-and-effect relationship between changes in the
      socioeconomic situation and medical workers' motivation to have information. The
      availability of various channels of medical information is regarded as low;
      specifically, the possibility of studying at courses for continuous education of
      physicians or individual studies of medical literature. The authors offer
      arguments proving the necessity of providing financial and economic, legal, and
      other types of information to physicians, for working under marketing relations
      is impossible without such information. The problem of information supply to
      physicians should be solved at the level of universal purposeful and steady state
      policy The authors come to a conclusion about the need in crucial reorganization
      in the sphere of scientific medical information and creation of a universal
      information space with obligatory analysis of the information requirements of
      medical workers.

PMID- 9244589
TI  - [The future of the development of medical prophylaxis for the population of the
      Russian Federation (according to the data of sociological studies)].
AB  - Sociological status and approaches to the development of the treatment and
      prophylactic care to the population of the Russian Federation were assessed using
      questionnaires distributed among heads of public health organs and institutions
      and physicians in various regions of the country. The majority of respondents
      consider the structural and functional reformation of the system of treatment and
      prophylactic care as absolutely necessary: the bed find structure is to be
      altered, scope of specialized care rendered on an outpatient basis increased, the
      rehabilitation and health fortification processes developed, and forms and
      methods of financing the public health institutions and of medical workers'
      payment improved at the expense of state sources (budget), medical insurance
      funds, and, partially, paid medical service.

PMID- 9244590
TI  - [On the scientific substantiation of specialization of family physicians
      practising at the resorts].

PMID- 9244591
TI  - [On the evaluation of the city children's dentist clinic].
AB  - The authors offer criteria to validate the choice of a pediatric dental clinic or
      another treatment-and-prophylactic institution, as exemplified by Moscow, as the
      base for the study of therapeutic and diagnostic activity. The mean values for a
      number of parameters were determined: hourly loading of dentists, frequency of x
      raying and physiotherapeutic procedures, sanitization of the oral cavity and
      teeth, etc., and deviations of the similar indexes at other outpatient clinics
      from these values, expressed in the mean square values. Summation of the mean
      square deviations with consideration for their positive or negative signs,
      followed by ranking of the data, helped determine an institution occupying an
      intermediate position, which, in author's opinion, indicates its typical
      character and, hence, should be preferable.

PMID- 9244592
TI  - [Medical service marketing at the time of medical insurance].
AB  - Presents the approaches to applying the fundamentals of marketing to public
      health. Medical insurance organization may effectively work as arbitrators and
      marketing agents; the basic assumption in the theory of marketing underlies their
      activity. The concept of marketing implies investigation of the requirements of
      the users of medical services and the development of measures aimed at meeting
      the requirements of man in terms of health service and health maintenance.

PMID- 9244593
TI  - [On the role of the teacher in the hygienic education of students].
AB  - The introduction of a valeology teacher at schools is proposed in order to form
      in children personal orientations and notions of health as an individual and
      social value. A variant of a part of the curriculum for teachers, devoted to
      fundamentals of a healthy life style, is presented.

PMID- 9244594
TI  - [Hippocrates and medieval medicine in Russia].

PMID- 9244596
TI  - Proceedings of the 9th Tokyo Institute of Psychiatry International Symposium.
      Tokyo, Japan, 26-27 October 1994.

PMID- 9244595
TI  - Richard L. Lindstrom, MD, 1995 Barraquer Lecturer, Biographical Sketch.

PMID- 9244597
TI  - Eradication or control?

PMID- 9244598
TI  - [Evaluation of the completeness of the epidemiological surveillance systems for
      malaria by the Capture-recapture system in the French armies in l994].
AB  - The Capture-recapture method has been utilized to evaluate the annual incidence
      of malaria in the French armies in 1994 on the basis of the incidence derived
      from two regulatory systems, passive and exhaustive, of epidemiological
      surveillance: the Recueil et l'Exploitation des Donnees Epidemiologiques des
      Armees (REDEA) and the Surveillance Epidemiologique du Paladisme (SESP) system.
      Cases of malaria found by REDEA and SESP in 1994 rose to 480 and 424
      respectively. Two hundred and thirty-eight cases were found by both systems.
      After validating the conditions for the application of the Capture-recapture
      method (in particular, having verified that the results from REDEA and SESP were
      probably independent), its utilization allowed us to evaluate the incidence of
      malaria in the French army in 1994 at 854 cases. The calculated exhaustivity
      values for REDEA and SESP were 56.2 and 49.6% respectively; 22% of cases were
      missed by both systems. The exhaustivity values of SESP and REDEA estimated in
      our study were comparable to those obtained by the Capture-recapture method
      applied in another legal inquiry into the passive and exhaustive epidemiological
      surveillance of meningitis and meningococcosis in France in 1989 and 1990. These
      results show that it is difficult to evaluate the epidemiological importance of a
      sickness on the results of passive and exhaustive surveillance alone. In 1995, a
      new system of surveillance was established in the army: a better conducted and
      more motivated retro-informative system, linked to a better education of medical
      officers in epidemiological surveillance permitted an improvement in the
      completeness of the results in the armies.

PMID- 9244599
TI  - Vulnerable groups at risk from "commercial" ethical review boards.

PMID- 9244600
TI  - American seeds suspected in Japanese food poisoning epidemic.

PMID- 9244601
TI  - Faster patents and longer lives for biotechnology products.

PMID- 9244602
TI  - British health service balks at cost of cancer trials.

PMID- 9244603
TI  - Breast cancer susceptibility tests still valid, companies argue.

PMID- 9244604
TI  - Myriad's rationale for wider testing.

PMID- 9244605
TI  - Cloning research a possibility.

PMID- 9244606
TI  - Insurers admit genetic discrimination.

PMID- 9244607
TI  - [Molecular genetic study in congenital myotonic dystrophy].
AB  - Congenital myotonic dystrophy (CMD) is the neonatal form of Steinert's myotonia.
      However, the symptoms and neuro-physiological findings are different from the
      classical adult form, there is a high mortality and early diagnosis of the
      condition is difficult. CMD occurs as a result of abnormal expansion of CTG
      triplets on chromosome 19. There is dominant autosomal transmission of this multi
      systemic disorder, although when it occurs in children, it is the mother who is
      always the affected parent. Molecular genetic techniques enable unequivocal
      diagnosis of the condition, evaluation of anticipation and the possibility of
      offering genetic counselling to the families involved.

PMID- 9244608
TI  - [Tonal dichotic listening: discriminatory value between left and right handedness
      and between sexes].
AB  - INTRODUCTION: The dichotic hearing test consists of simultaneous stimulation of
      right and left ears with different messages, allowing analysis of the better or
      worse selective integration of these messages. MATERIAL AND METHODS: With the
      latest techniques, the tonal dichotic test is applied by listening to a sample of
      90 persons, ages from between 20 and 50 years without antecedents of otologic,
      neurologic nor psiquiatric disorders, valuing their discriminative and dominant
      capacity for lateral hearing. RESULTS: The test is chosen effectively arranging
      the persons by their stereophonic capacity, like something adding but is as not
      as their simple biaural hearing capacity is, it is found an average capacity of
      hearing of the 79.856% in the left ear while there is only in 74.856% of in the
      right ear, which represents a dominance or increased value for the left ear.
      CONCLUSIONS: Separating within the general sample the right-handed (60 persons)
      from the left-handed (30 persons), there is not found any meaningful differences
      neither concerning capacity of discrimination nor of dominance. Separating them
      by sexes (58 women and 32 men) no meaningful differences are found either in
      discriminative capacity or in dominance.

PMID- 9244609
TI  - [Physiopathology of amyotrophic lateral sclerosis: the contribution from
      transcranial magnetic stimulation].
AB  - INTRODUCTION/OBJECTIVE: The introduction of the technique of magnetic stimulation
      for the study of motor disorders has led to a better understanding of the
      pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS).
      MATERIAL AND METHODS: Thirty two patients with ALS were studied in order to
      describe the behaviour of the variables: central conduction time (CCT), amplitude
      ratio (Ar) and motor threshold (MT) evaluated by means of motor evoked potentials
      (MEP). RESULTS: Analysis of these variables showed the great sensitivity of MEP
      for the detection of abnormalities in the corticospinal tract with 95% of the
      results being abnormal. Subclinical abnormalities were detected in 22.4% of
      recordings. Axonal degeneration was the commonest kind of conduction disorder
      seen. A significant lineal relationship between the evolution time and the
      variables MT, Ar and CCT (p < 0.05) was demonstrated. This suggests that there is
      a progressive deterioration of the voluntary motor pathway which begins with an
      excitotoxic mechanism at the onset of the disease and ends with the death of
      motor neurones. CONCLUSIONS: The electrophysiological results discussed, together
      with observations on isolated cases provide evidence in favour of the hypothesis
      of degeneration of the upper motor neurone. Although it is recognized that this
      alone does not explain the whole degenerative phenomenon of the motor system
      which occurs in ALS.

PMID- 9244610
TI  - [Muscarinic receptors on lymphocytes].
AB  - INTRODUCTION: The presence of muscarinic receptors on lymphocytes and possible
      modifications in their number and affinity may be related to cholinergic changes
      found in muscarinic receptors at a central level. OBJECTIVE: The objective of
      this paper is to bring the technique for the determination of lymphocyte
      muscarinic receptors by means of their union with radioligands for application in
      the study of disorders involving the cholinergic system, such as Alzheimer's
      disease, up to date. MATERIAL AND METHODS: We therefore made a density gradient
      isolation of lymphocytes from healthy subjects and made a trial of union or
      binding with N-methyl-escopolamine marked with tritium (3H-NMS) on intact
      lymphocytes. RESULTS: We were unable to specifically label the muscarinic
      receptors. However, we have shown the usefulness of the technique, using rat
      anterior cerebral homogenate. CONCLUSIONS: We consider whether the absence of
      specific union with the lymphocyte muscarinic receptor is due to technical
      problems as is often described in the literature, or possibly due to the absence
      of these receptors on the lymphocyte as suggested by other authors and proved
      using molecular biology techniques to be the case for the M2 receptor subtype.

PMID- 9244611
TI  - [Cardiovascular changes in a group of patients with heredoataxia. Clinical,
      electrocardiographic and echocardiographic findings].
AB  - INTRODUCTION: Heredoataxias form a group of degenerative diseases of the nervous
      system, which are progressive and hand sound in particular families. MATERIAL AND
      METHODS: Between August 1994 and September 1995. 14 patients diagnosed as having
      heredoataxia were studied after admission to our hospital. Eight of these had
      Friedrich's ataxia (group A) and 6 had other types of ataxia (group B). A
      standard set of investigations were done, including clinical examination,
      laboratory tests (such as glycaemia and a lipidogram) to evaluate coronary risk
      factors. A 12 lead electrocardiogram and bidimensional and m mode echocardiogram
      were also done to detect disorders of conduction, changes in morphology and
      cardiac function, together with functional cardiovascular and neurological
      scales. The patients studied were between 14 and 41 years of age. RESULTS: The
      most frequent cardiovascular symptom was dyspnoea of effort. Changes on the
      electrocardiogram were seen in 92% of the patients, mainly from Group A (100%)
      and were due to alterations of ventricular repolarization and non-specific
      alterations of conduction and of rhythm. Echocardiogram changes were found in
      42.8% of the patients, most frequently due to an increase in the myocardial mass
      of the left ventricle. CONCLUSIONS: Close correlation between age of onset and
      duration of the illness, and functional cardiovascular impairment was only seen
      in patients of Group A, in whom there was an earlier onset of the condition.

PMID- 9244612
TI  - [Follow-up study of the evolution of the quantitative EEG in intraventricular
      infusion of nerve growth factor in an aged baboon].
AB  - The animal model of aged monkeys is a good homologue of Alzheimer's disease in
      humans, in which it has been shown that there is disproportionate slowing of the
      EEG when compared with healthy subjects paired for age. This is found both on the
      conventional EEG and quantitatively. In the latter, relative energy has been the
      measurement most commonly used for diagnosis and follow-up with various
      treatments. The follow-up parameters evaluated in this study were: absolute and
      relative energy of the quantitative EEG (EEGq) obtained in an aged (39 year old)
      baboon (Papio hamadryas) before and after infusion of intraventricular nerve
      growth factor (NGF). These findings were compared with those of a young animal (6
      year old) of the same species, treated in the same way. Since the animals were
      first anaesthetized with ketamine and diacepam so as to be able to carry out the
      study, we used a cerebral function analyzer which allowed us to ascertain that
      the changes found on analysis of the EEGq were not due to the depth of
      anaesthesia. The analyzer evaluated the tendencies of amplitude and frequency of
      the EEG, which is a method widely used for the indirect evaluation of the level
      of anaesthesia.

PMID- 9244613
TI  - [The medical care of patients with Parkinson's disease in a general hospital].
AB  - INTRODUCTION: The Parkinsonian syndromes create an important need for local
      health care mainly at the level of hospital outpatient departments or health
      centres. OBJECTIVE: In this article we analyze the neurological attention
      received by this group of patients in the setting of a general hospital with a
      system of providing care for such patients involving little contact between the
      hospital neurological department and the neuropsychiatric services available at
      the level of health centre. MATERIAL AND METHODS: A retrospective study was made
      of the medical care given to a group of 63 patients seen in the neurological
      department of Hospital General de Castellon. The frequency of visits to the
      hospital outpatient department was 0.12/1,000 inhabitants/year for the first
      visit and 2.25/1,000 inhabitants/year for second visits. This was 5.5% and 15%
      respectively of the total patients seen in the outpatient department. Hospital
      admission of Parkinson patients to the Neurology ward for causes directly related
      to their condition made up 1.37% of all neurology admissions and 0.04% of the
      total hospital admissions during the period studied. We found that in our
      hospital practice only a small number of patients with this disease were attended
      and these were late in reaching our clinic. Usually they were referred by the
      rehabilitation and rheumatology departments rather than the neuropsychiatric
      services at the health centre hospital outpatient. CONCLUSIONS: It is necessary
      to study how neurological care of this group of patients can be standardized in
      our community and to clearly define the minimum requirements and place of each
      level of care involved in the treatment of this group of patients.

PMID- 9244614
TI  - [Clinico-pathological study of cerebral death].
AB  - INTRODUCTION: We present the experience of the Hospital Provincial Clinico
      Quirurgico Saturnino Lora, Santiago de Cuba, in the clinical study of brain
      death. MATERIAL AND METHODS: We studied 27 cases admitted to hospital between
      1994 and 1995. In 74.07% of these cases organ extraction was carried out. The
      most commonly affected age group was between 20 and 29 years old, which made up
      more than half of the total number of cases, with a predominance (81.5%) of
      males. RESULTS: Cranio-encephalic injury was the commonest cause, in particular
      severe cerebral contusion and primary brain stem contusion. The patients had
      brain death lasting between one and five hours and one for 38 hours. Respiratory
      sepsis was the most frequent associated pathology. Computerized axial tomography
      and straight X-rays were the imaging techniques most commonly used in the
      diagnosis of brain death. Severe cerebral oedema was the most frequent
      anatomopathological finding and was seen in all cases in which necropsy was done,
      followed by herniation of the cingulum in 23 cases (88.4%) and cerebral necropsy
      in 20. CONCLUSIONS: These anatomopathological results show the severe damage
      suffered by cerebral structures.

PMID- 9244615
TI  - [Pure alexia: presentation of three cases and review of the literature].
AB  - INTRODUCTION: Pure alexia is a syndrome characterized by the inability to read
      aloud in the absence of agraphia or apnasia. CLINICAL CASES: Three clinical cases
      showing this syndrome are presented. Case I had a left occipital lesion
      compatible with a subacute haematoma. He had problems with reading, visuo-spatial
      recognition, digital gnosia and memorizing texts. One year later there was
      considerable improvement in most of the sub-tests evaluated. There was still
      deficient colour naming right/left orientation and understanding of letters and
      words. Case 2 presented with a right homonymous hemianopia and slight left
      paresis. He had a small left occipital ischaemic infarct. One year later there
      was improvement on testing, with some deficit still in visual recognition, naming
      colours and memory. Case 3 presented with right homonymous hemianopia, slight
      right paresis and a left occipito-parietal expansive lesion. He had defective
      reading, choosing and naming of colours, right/left orientation and memory. On
      later evaluation, considerable improvement was seen. There was still colour
      agnosia, although less severe and mild 'laziness' of the right side. CONCLUSIONS:
      In the review of the literature, the disorder and the contributions of various
      authors, from Deperine in 1892 to the present day, are considered in detail.

PMID- 9244616
TI  - [Myopathy caused by inhibitors of hydroxymethylglutaryl-coenzyme A reductase].
AB  - INTRODUCTION: Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) Reductase inhibitors are
      a group of drugs widely used for hypercholesterolemia. They are known to
      originate side-effects on muscles but with a very low incidence of myopathy.
      CLINICAL CASE: We present two cases of myopathy induced by HMG-CoA reductase
      inhibitors. They are two women, who were on 20 mg daily of lovastatin and 30 mg
      daily of simvastatin and consulted due to weakness, myalgia and a rise in blood
      levels of muscle enzymes. Both of them recovered completely a few weeks after
      withdrawal of the drugs. COMMENTS: Usage of this group of drugs is wide. Their
      side effects are rare but it is important to remember their capacity to induce a
      myopathy, usually reversible upon withdrawal of the drug.

PMID- 9244617
TI  - [Dolichoectasia of multiple cranial arteries. Findings on neuroimaging and
      transcranial Doppler].
AB  - INTRODUCTION: Dolichoectasia of the intracranial arteries may give rise to
      ischaemic or haemorragic pathology and to compression phenomena. Joint
      dolichoectasia of the whole circle of Willis, in both the anterior and basilar
      portions extending to the main basal arteries is an unusual finding. CLINICAL
      CASE: We describe a 76 year old man who presented with vertigo with vertically
      downward nystagmus. On neuroimaging studies there was aneurysmal dilation of the
      left vertebral, basilar and both carotid arteries (in their supra-clinoid
      portion) and of both medial cerebral arteries. Transcraneal Doppler showed marked
      reduction in flow rate with normal morphology and pulsation. CONCLUSION: The
      combination of non-invasive techniques allows full, reliable evaluation of the
      swollen arteries and possible complications.

PMID- 9244618
TI  - [Late onset of pseudobulbar paralysis and dystonia in a case of hemispheric
      cortical dysplasia].
AB  - The atypical clinical course of a young male with encephalopathy due to right
      hemispheric cortical dysplasia (pachygiria) is described. From the first months
      of life the course of the disease was a static encephalopathy with left
      hemiparesis, epilepsy and mild mental retardation. When he was 14 years old a
      subacute pseudobulbar palsy, dystonia and spread of the paresis to the right side
      occurred. Epileptic seizures, paroxysmal EEG abnormalities and drug ingestion
      were excluded. Neuropsychological studies showed a low level of cognitive
      functions, probably related to the malformative encephalopathy and expressive
      language deficit due to the pseudobulbar paresis. We speculate that this case
      could be an atypical case of delayed onset dyskiesia.

PMID- 9244619
TI  - [Low grade disseminated astrocytoma in childhood].
AB  - INTRODUCTION: Leptomeningeal dissemination is a common event in some kinds of
      cerebral tumours, but in low-grade astrocytomas who classically have been
      conferred a benign course. However, multifocal affectation is described each time
      more frequently in these group of tumours. CLINIC CASES: We present three
      patients aged respectively 8 and 10 months and 10 years, who were diagnosed of
      low-grade astrocytoma with multicentric spread. They were treated with systemic
      chemotherapy and controlled with MRI. At the end of the treatment an important
      reduction in tumours' size was observed in the three cases. DISCUSSION:
      Biological behaviour of low-grade astrocytoma as been reviewed in last years. By
      one side, it has been seen that certain histological characteristics are
      associated with an aggressive behaviour: on the other hand, long-term evolution
      of these tumours can be complicated with tumoral recurrence, malignization and
      leptomeningeal dissemination. This last one is observed each time more frequently
      since the use of MRI in the diagnose of cerebral tumours has become routine. From
      the therapeutic point of view, chemotherapy represents an effective choice for
      these patients' management, when surgery is not possible and radiotherapy not
      advisable, allowing in many cases to stop tumoral growth and sometimes to reduce
      it's size strongly.

PMID- 9244620
TI  - [Dissection of the internal carotid artery with subarachnoid hemorrhage].
AB  - INTRODUCTION: Dissection of the intracranial arteries is uncommon, forming less
      than 10% of all cranio-cervical dissections. Apart from the classical clinical
      findings of extracranial dissections, intracranial dissection may cause
      subarachnoid haemorrhage (SAH), mainly dissections involving the posterior
      circulation. CLINICAL CASE: We describe the case of a 49 year old man, a smoker,
      who had a sudden onset of headache followed by loss of consciousness. On CT there
      was SAH and multiple cerebral infarcts. Arteriography showed findings compatible
      with dissection of the extracranial and intracranial carotid arteries.
      DISCUSSION: We discuss the epidemiology and mechanisms of SAH associated with
      intracranial dissections. Intracranial dissection. Intracranial dissection should
      be considered in the differential diagnosis of SAH and of ischaemic syndromes.

PMID- 9244621
TI  - [Osterosclerotic myeloma and polyneuropathy].
AB  - INTRODUCTION: The peripheral neuropathy is a common complication in patients with
      osteosclerotic myeloma. The association with hepatosplenomegaly, lymphadenopathy
      and variable endocrine disturbances and skin changes constitute the POEMS
      syndrome. The pathogenesis of this syndrome is unclear, but the presence of M
      protein and elevated levels of interleukin-6 in the serum of patients, suggests
      an immunologic mechanism. CASE: A 68 year old woman presented with a 2 year
      history of progressive weakness and paresthesias in both legs. Neurological
      examination revealed a sensorimotor polyneuropathy, involving predominantly the
      lower extremities. In addition to neurological findings, the patient had
      lymphadenopathy and skin hyperpigmentation. Serum protein immunoelectrophoresis
      revealed a peak of monoclonal IgA lambda paraprotein. Radiographic examination
      disclosed multiple osteosclerotic lesions. Electrophysiological evaluation showed
      a severe axonal and demyelinating sensorimotor polyneuropathy. Biopsy of sural
      nerve revealed demyelination and axonal degeneration. Axillary lymph node biopsy
      were consistent with giant lymph node hyperplasia. Interleukin-6 serum levels
      were normal. CONCLUSIONS: The POEMS syndrome or Crow-Fusake syndrome is a rare
      multisystem disorder often associated with osteosclerotic myeloma. A severe
      demyelinating sensorimotor polyneuropathy frequently constitutes the chief
      complaint. These patients have a polyneu-ropathy which resembles idiopathic
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the
      electrophysi-ological studies are essential in the diagnosis. The pathogenesis
      has not been explained. Presumably, the plasma cells secrete an immunoglobulin or
      another substance that is toxic to peripheral nerves. Interleukin-6 is implicated
      in the pathogenesis of this disease.

PMID- 9244622
TI  - [Perceptive deafness and AIDS].
AB  - We report a case of a 23 years old woman HIV positive for the past five years
      with a four year history of right perceptive hypoacusia evolution without
      tinitus, vertigo or any other otologic symptomatology. After reviewing her
      personal and family history and conducting imilar tonal audiometry, tympanometry
      bilateral, contralateral estapedial reflex, auditory evoked brain stem response
      and a bilateral nasal fiberendoscopy, we analyzed the evolution of her immunal
      deficiency and the treatments to which she has been submitted with the purpose of
      determining the risk factors that have coincided in this case to be able to
      establish some criteria to follow the auditive affect in HIV positive patients.

PMID- 9244623
TI  - [Spontaneous acquired localized neuropathies in childhood].
AB  - Acquired non-surgical, non-traumatic localized neuropathies, excluding cranial
      nerve disorders, are rare in infancy. We review the clinical histories of six
      children, studied for this disorders amongst a total of 2,105 children seen in
      the Neuropediatric Department of the Hospital Miguel Servet in Zaragoza. Two were
      diagnosed as familial neuropathy with pressure sensitive paralysis. Two
      plexopathies were considered to be familial brachial plexopathy with minor
      dysmorphic features. One case was diagnosed as idiopathic radial neuropathy and a
      further case as idiopathic lumbosacral plexopathy. We emphasize that although
      rare in pediatrics, spontaneous localized neuropathies often show constitutional
      pathology, frequently hereditary. Idiophatic cases may also be hereditary, and it
      may be difficult to confirm the diagnosis if there is no family history or
      phenotypic characteristics. Diagnosis depends on the personal and family history,
      physical examination, neurophysiological study, absence of abnormal neuroimaging
      findings and awareness of the possibility of this diagnosis. These disorders
      probably occur more often than is generally believed.

PMID- 9244624
TI  - [Acupuncture and neurology].

PMID- 9244625
TI  - [Tuberculous meningoencephalitis].
AB  - Tuberculosis (TBC) in children is still a public health problem in developing
      countries. Its most serious complication in children is meningo-encephalitis (ME
      TBC), which is one of the main causes of death from TBC. The objective of this
      review is to outline its aetiopathological, clinical and prognostic
      characteristics and compare these with three studies made in our University
      between 1984 and the present time. METBC is always a complication secondary to an
      unknown (but often pulmonary) focus. The morbid anatomy of the deposit of basal
      exudate explains all the subsequent clinical findings. The data given in the
      literature regarding the commonest presentation, that of subacute or chronic
      meningo-encephalitis, is similar to our findings. However there are some
      differences. These are: a tendency to presentation in older children, much lower
      mortality, a long-term incidence of sequelae of less than 50% which is much less
      than would be expected (especially in certain areas of superior nerve function).
      With regard to treatment, we emphasize that the standard recommendation is still
      to use four drugs for twelve mouths. Although steroids have not been shown to be
      of use with regard to either mortality or morbidity, they continue to be given.

PMID- 9244626
TI  - [Neuro-AIDS].
AB  - The human immunodeficiency virus (HIV) type 1 is the retrovirus which is
      responsible for the human immunodeficiency syndrome (AIDS) described in infancy
      in 1983. It is the most serious disorder caused by HIV, by a neurotropic virus,
      and is particularly severe in infancy. In children infected by vertical
      transmission of HIV, there is a shorter clinical latent period than in adults,
      and more viraemia than in children over the age of three months infected by blood
      transfusion. The neurological disorder caused by HIV is a complex clinical
      syndrome in which there may be varying degrees of retardation of cognition,
      movement or behaviour. A growing number of HIV+ children are being followed-up in
      the Hospital de Clinicas de Porto Alegre (HCPA) to treat the neuropsychomotor
      development and the presence of neurological behaviour in these children. The
      neurological, analytical (laboratory), electro-encephalographic and tomographic
      changes seen in a sample of 344 HIV+ children were studied. Analysis of these
      results showed a significant difference between affected and non-affected
      children. Encephalopathy occurred in 36% of the cases, being progressive in 29%
      and static in 17%. There was a relationship between neurological involvement at
      the first consultation and progress to encephalopathy. The RDNPM showed a
      tendency towards encephalopathy, usually between 1 and 5 years of age, which
      might also be the first sign of the disease. We found a significant relationship
      between being infected and having alterations not seen in cerebrospinal fluid,
      EEG, TCC and neurological progress.

PMID- 9244627
TI  - [Post-infectious demyelinating diseases].
AB  - Post-infectious demyelinating disorders are uncommon. In the Hospital Pediatrico
      de la Misericordia de Santafe de Bogota there were 14 cases in three years. The
      commonest age group was the new born, as is found in the literature. The
      infections involved in these neurological changes are probably viral, since at
      the time the patient is seen most symptoms have cleared up spontaneously.
      According to several authors, the viruses are most often found to be those of
      measles or mumps. Between the infection and the development of neurological
      symptoms there is an interval of approximately two weeks. The main clinical
      findings are motor changes such as hemiparesis, involvement of cranial nerves and
      alterations of consciousness. The aetiology is not completely clear. Firm
      diagnosis is made on histopathological studies which are seldom available.
      Usually neuroimaging techniques and cerebrospinal fluid analysis are the basis of
      the diagnosis. Computerized axial tomography and magnetic resonance are the most
      useful noninvasive techniques for assessing the involvement of the white matter,
      the extent and sites of the lesions. It is useful to know the classification of
      the demyelinating disorders so as to prescribe, the most suitable treatment and
      give the prognosis in each case. There is still no specific treatment for these
      disorders. Supportive measures, the control of epileptic crises and the
      prevention of complications are the main aims. This paper reviews the definition,
      classification, diagnosis and management of these disorders.

PMID- 9244628
TI  - [Viral encephalitis].
AB  - Viral infections of the nervous system make up a wide range of disorders with a
      mainly benign outcome. However, in some cases there is severe, morbimortality. In
      viral encephalitis there is direct involvement of the brain parenchyma which is
      seen clinically as reduced consciousness, convulsions and/or focal neurological
      deficit. The especial attraction of some viruses for particular cells or
      structures determines the variety of clinical findings. The incidence and
      frequency of the various agents depends on several factors (geographical location
      of a certain virus, age and general health of the population concerned, etc.). In
      areas free of arbovirus the commonest aetiologies are; varicella, herpes simplex,
      parotiditis and enterovirus. Modern treatment (transplants, chemotherapy) of
      previously fatal diseases and the AIDS epidemic have increased the number of
      immunodeficient patients; the population is susceptible to viral infections of
      the nervous system which are infrequent (e.g. cytomegalovirus, papovavirus) or
      which follow a different course (e.g. measles, enteroviruses) to that in
      immunocompetent patients. Specific conditions are reviewed. Improvement in the
      general health and sanitation of the population, and the universal use and
      development of new vaccines will significantly reduce the incidence of viral
      encephalitis. Improved prognosis will be related to the use of modern laboratory
      techniques which permit early, sensitive, specific diagnosis and the development
      of antiviral agents.

PMID- 9244629
TI  - [Stroke in teenagers].
AB  - Between 3.7% and 8.5% of all strokes occur before the age of 45 years old. In the
      population under 15 years of age, the annual incidence of strokes is 2.7 per
      100,000 children, with ischaemic strokes making up 1.2 and haemorrhagic strokes
      1.5 of this total. The main characteristic of ischaemic strokes in childhood is
      the wide variety of diagnoses involved. Some of these, such as congenital
      cardiopathy, are rare in adults, as are dissections and arterial dysplasias,
      arteritis, hereditary connective tissue disorders and disorders of metabolism.
      Similarly, the aetiology of haemorrhagic stroke is also very varied, with
      bursting of a vascular malformation or aneurysm being the commonest. Other
      aetiologies are disorders of haemostasis, arteritis, migraine, retarded post
      traumatic phenomena and the use of drugs and sympathomimetic agents. The
      personal, family and social repercussions are considerable, since both ischaemic
      and haemorrhagic strokes have an appreciable mortality and morbidity.

PMID- 9244631
TI  - [Posterior fossa tumors in children].

PMID- 9244630
TI  - [Stroke therapy in children].
AB  - OBJECTIVE: To evaluate the treatment modalities used in children (ages 1-18
      years) with cerebral infarction. BACKGROUND: [corrected] Cerebrovascular disease
      in children is more common than once suspected but its treatment has not been
      rigorously studied. MATERIAL AND METHODS: We reviewed all cases of cerebral
      infarction at the James Whitcomb Riley Hospital for Children at the Indiana
      University Medical Center from 01.01.80 to 31.12.95. RESULTS: Ninety-three
      children who experienced ischemic strokes were followed over the past fifteen
      years. Fifty-seven males and thirty-six females comprised the sample. Mean age
      was 6.9 years at the time of stroke. No medication or surgical intervention was
      the therapeutic recommendation in 44% of patients. For cardioembolic strokes,
      warfarin was used later in the course for a few patients who went on to have
      atrial fibrillation or valve replacement. Aspirin was used in all patients with
      carotid artery dissections. Aspirin was used in most children with Moya-Moya,
      with calcium channel blockers and surgical intervention used in later cases.
      Exchange transfusion followed by monthly transfusion and chelation therapy has
      been the treatment of choice for children with cerebral infarction complicating
      sickle cell disease. CONCLUSIONS: In most instances, treatment was widely
      disparate, probably reflecting the lack of firm therapeutic guidelines for this
      age group, with a better understanding of the etiology and pathophysiology of
      strokes in children, multicenter, international, randomized therapeutic trials
      based strictly on an etiological basis should be organized in the future.

PMID- 9244632
TI  - [Neuroendoscopy: diagnosis and therapeutic uses].
AB  - Minimally invasive neurosurgical techniques permit improved ways of approaching
      problems which could previously only be solved by open surgery or microsurgery.
      In this field, neuroendoscopy offers a very efficient, clear means of diagnosis
      and a less aggressive form of treatment of lesions on the central nervous system.
      Particularly in paediatric neurosurgery, procedures such as implanting valves for
      ventriculo-peritonial derivations (DVP) may be carried out knowing the exacts
      anatomical site of the catheter tip, or allowing catheters adherent to structures
      such as the choroid to be removed. Ventriculoscopy permits review and biopsy of
      intraventricular and paraventricular structures. Myeloscopy allows intramedullary
      and paramedullary visualization together with the possibility of syringoscopy.
      The new option presented by neuroendoscopy, as a help in microneurosurgery, when
      studying structures which are not visible using a microscope, is particularly
      useful in vascular surgery and in surgery of the base of the skull. It also
      permits rapid, efficient drainage of subdural and intraventricular haematomas.
      This technique has become a useful tool in neurosurgical departments for solving
      problems and as a support for the classical techniques. Equally it requires
      practice and the study of neuroendoscopic anatomy.

PMID- 9244633
TI  - [Sclerotic subacute panencephalitis: data on 1997].

PMID- 9244634
TI  - [Parkinsonian syndromes in children].

PMID- 9244636
TI  - Peer review and the entrepreneurial spirit.

PMID- 9244635
TI  - [Demyelinating diseases in childhood: diagnostic contribution of magnetic
      resonance].
AB  - Magnetic resonance imaging (MRI) exhibits a high sensitivity to detect white
      matter alteration but lacks specificity to characterize the disorder. We focus on
      the differential MR finding In two supposed autoimmune demyelinating diseases:
      multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). In ADEM,
      the associated finding of T2 prolongation in deep gray matter, specially the
      thalamic involvement, is a useful distinguishing feature. Given that ADEM is
      usually a monophasic disease the lesional enhancement should be homogeneous, and
      new lesions would not be expected to occur in serial MRI. Advances in
      neuroimaging of myelin disorders are intended for improve the resolution and
      sensitivity of MRI and for research new techniques to quantify lesion load and to
      monitor demyelination and neuronal damage.

PMID- 9244637
TI  - 1st International Congress on MR Mammography. Jena, Germany, 29-31 May 1997.
      Abstracts.

PMID- 9244638
TI  - Proceedings of the 1st International Symposium of Neurovirology. Philadelphia,
      Pennsylvania, 5-7 May 1997.

PMID- 9244639
TI  - [The "twist" is good for the heart].

PMID- 9244640
TI  - [Minimally invasive coronary surgery].

PMID- 9244641
TI  - [Cardiac emergencies in the community].

PMID- 9244642
TI  - [Cryopreserved homograft cardiac valves: structural modifications brought about
      by the use of sterilization and cryopreservation methods].

PMID- 9244643
TI  - [The relationship between regional sympathetic activity and the onset of arterial
      hypertension in spontaneously hypertensive rats].
AB  - Several studies on spontaneously hypertensive rats (SHR) have demonstrated
      increased activity of the sympathetic nervous system (SNS). Using microdialysis,
      we have observed a greater release of norepinephrine (NE) into the interstitia of
      striated muscle, than that observed in control Wistar-Kyoto (WKY) rats in the
      prehypertensive phase. We confirmed these results in the subcutaneous adipose
      tissue where the sympathetic output controls metabolism. This study was carried
      out in order to evaluate SNS activity in two district tissue types conducted
      during both the prehypertensive phase (4-5 weeks of age) and the established
      hypertensive phase (15-16 weeks of age). Interstitial concentrations of NE were
      measured by microdialysis in striated muscle and subcutaneous adipose tissue. Two
      groups of rats were studied. Each group was made up of 8 subjects, SHR and WKY,
      males of 4-5 weeks of age with a mean body weight of 80 and 75 g respectively.
      Arterial systolic pressure (tail-cuff) values were 106 mmHg (standard deviation
      +/-8.2) in SHR and 101 mmHg (standard deviation +/-6.9) in WKY rats (NS). Two
      microdialysis probes were positioned in the subcutaneous fatty tissue and in the
      striated muscle of the parascapular region and perfused with Ringers' solution.
      The dialysate was collected every 30 min for 150 min and analyzed in high
      performance liquid chromatography-every day. The content of NE and other
      catecholamines was determined. The same animals in both groups were reevaluated
      at 15-16 weeks of age. The mean body weight at this time was 246 g for the SHR
      and 289 g for the WKY rats. Arterial systolic pressure was 161 mmHg (standard
      deviation +/-13.3) and 108 mmHg (standard deviation +/-15.6) respectively (p <
      0.01, Student's t test). Interstitial levels of NE were higher in SHR than in WKY
      rats in both tissues examined in the prehypertensive phase and in the established
      hypertensive phase. Mean NE values from subcutaneous adipose tissue in 4-5 week
      old SHR were 1362.1 +/- 181.3 pg/ml compared to 479.0 +/- 162.3 pg/ml in WKY rats
      (p < 0.001, Student's t test). Muscle tissue NE levels in SHR were 1292.7 +/-
      319.1 vs 536.3 +/- 146.7 pg/ml in WKY rats (p < 0.001, Student's t test). Values
      from the same rats at 15-16 weeks of age were 1405.0 +/- 148.3 pg/ml in SHR
      compared to 501.6 +/- 131.2 pg/ml in fatty tissue from WKY rats and 1893.7 +/-
      214.6 vs 502.0 +/- 118.8 pg/ml in muscle tissue from the respective groups (p <
      0.001, Student's t test). Significant differences (p < 0.01, Student's t test)
      were also observed in mean NE values in striated muscle tissue during the
      developing phase of hypertension. These findings document SNS hyperactivity in
      SHR when compared to WKY normotensive controls. This increase in SNS activity was
      observed in both the prehypertensive phase and in the established hypertensive
      phase indicating a complete disassociation from regional components of regulation
      (baroreceptor control and metabolic control), at least in the prehypertensive
      phase. These results may suggest as alteration in primitive sympathetic central
      outflow. Higher interstitial NE concentrations in the muscle tissue from SHR
      during the hypertensive phase compared to levels of young animals that are still
      normotensive, reveal an interesting pathophysiological aspect for the development
      of arterial hypertension.

PMID- 9244644
TI  - [Effectiveness and tolerability of bisoprolol vs. nifedipine in uremic patients
      with ischemic cardiopathy in dialysis treatment].
AB  - The effects of bisoprolol on transient myocardial ischemia have been compared
      with those of nifedipine in patients with coronary artery disease in end-stage
      renal failure maintained on haemodialysis. We also evaluated the tolerability of
      both drugs. Sixty patients (42 males, 18 females, mean age 52 +/- 4 years) in
      renal failure maintained on haemodialysis, with coronary artery disease and more
      than four significant episodes of transient myocardial ischemia (> or = 1 min)
      during 48-hour Holter monitoring, were included in the study. All cardiovascular
      drugs were discontinued > or = 6 days before this 48-hour ambulatory ECG
      monitoring, with the exception of sublingual nitrates allowed for relief of
      anginal attacks. Patients were then randomized to receive either bisoprolol or
      nifedipine for 2 weeks. After a 15-day wash-out period, they were crossed over to
      receive either bisoprolol or nifedipine for other 2 weeks. Statistical analysis
      was carried out using the Student's t test. A p value < 0.01 was considered
      significant. Both bisoprolol and nifedipine reduced number and duration of
      transient ischemic episodes as well as the total ischemic burden. Reductions were
      statistically significant for both antianginal drugs. Only bisoprolol was
      effective in silent ischemia (p < 0.001). It also reduced heart rate (p < 0.001),
      while nifedipine raised it (p < 0.001). Both drugs reduced systolic and diastolic
      blood pressure. The circadian variations of transient ischemic episodes showed
      two peaks in the 24 hours. Both peaks were reduced with bisoprolol. Nifedipine
      brought a clear overall reduction in the number of episodes but the circadian
      pattern was unchanged. During the study, 10 patients taking bisoprolol and 12
      patients taking nifedipine had drug adverse effects. No one of them had to be
      withdrawn from treatment. In conclusion, bisoprolol seems to be more useful than
      nifedipine because its effects, in transient ischemic episodes, are greatly
      superior to those of nifedipine, and because it is effective also in silent
      ischemia. Both drugs showed a good tolerability in these patients. Bisoprolol,
      reducing the two daily peaks of ischemic episodes frequency, has a protective
      role towards mortality due to coronary artery disease.

PMID- 9244645
TI  - [Troponin T, Troponin I and CK-MB (mass) in the detection of periprocedural
      myocardial damage after coronary angioplasty].
AB  - The development of methods for the detection of circulating CK-MB mass, cardiac
      troponin T (cTn-T) and troponin I (cTn-I) has increased the diagnostic potential
      in the identification of myocardial damage. Coronary angioplasty (PTCA)
      represents a widely accepted revascularization procedure and a clinical model of
      induced ischemia. Using these new biochemical markers, we evaluated the incidence
      and the clinico-procedural correlates of minor myocardial damage (MMD) in a
      series of patients treated with PTCA in our Department. In 57 consecutive
      patients (75% males; mean age 58 years; range 35-80) undergoing elective PTCA
      from March 1 to June 30, 1995, serum levels of CK-MB mass, cTn-T and cTn-I were
      measured at baseline and at 6, 12 and 24 hours after the procedure. Seventy-eight
      coronary stenoses were dilated (mean 1.4 lesion/patient), 17 of these were in
      infarct-related vessels; 8 were total occlusions and 2 were located in saphenous
      vein grafts. Twenty-two procedures were completed by coronary stenting (17
      elective). cTn-T and cTn-I were considered abnormal when serum levels were > 0.2
      ng/ml and > 0.6 ng/ml, respectively. CK-MB mass was also determined in all
      patients (abnormal > 5 ng/ml). No patients had clinical or electrocardiographic
      evidence of myocardial infarction after the procedure. Overall, 16 patients (28%)
      developed biochemical evidence of post-procedural MMD (defined as the presence of
      at least one abnormal sample of any among the three markers tested). Four (7%)
      had abnormal CK-MB mass (at least one sample), 9 (16%) abnormal cTn-T, and 15
      (26%) abnormal cTn-I. When CK-MB mass was elevated, both cardiac troponins were
      also elevated. In patients positive for MMD and abnormal CK-MB mass, peak cTn-I
      was significantly higher than in patients with normal CK-MB (3.02 +/- 1.07 vs
      1.02 +/- 0.11 ng/ml; p = 0.009). The difference was not evident when comparing
      the same groups of patients for cTn-T (0.26 +/- 0.04 vs 0.18 +/- 0.10 ng/ml; p =
      0.16). Also, peak cTn-I but not peak cTn-T had a positive correlation with peak
      CK-MB mass (r = 0.89; p < 0.0001 and r = 0.23; p = 0.40). The elevation of either
      marker of MMD was not related to clinical, angiographic or procedural variables.
      A possible interpretation for MMD was found in 2/3 of cases: bail-out (2); late
      occlusion (1); minor side branch occlusion (3); distal embolization from
      saphenous vein grafts (2) or total occlusions (2). In our series, MMD after PTCA
      occurs in 28% of cases and is unrelated to clinical, angiographic and procedural
      variables. Both cTn-T and cTn-I increase the sensitivity of CK-MB mass in the
      detection of MMD after PTCA, cTn-I being the most sensitive marker. In about 1/3
      of cases, the presence of MMD remains unexplained. The prognostic implications of
      MMD are as yet undefined.

PMID- 9244647
TI  - [Sarcoidosis with predominant cardiac involvement].
AB  - We present a case of predominantly myocardial sarcoidosis in a 38 year-old man. A
      second degree atrioventricular block was the clinical presentation, followed 2
      years later by sudden cardiac arrest. Autopsy revealed large areas of myocardial
      scarring in the left ventricular wall unassociated with atherosclerotic coronary
      lesions; microscopy of these areas disclosed epithelioid granuloma with giant
      cells embedded in a fibrohyaline tissue. The insidious cardiac involvement in
      sarcoidosis often hinders an exact diagnosis in life, and prognosis without
      therapy is severe. Histopathologic diagnosis is made only by exclusion of other
      systemic granulomatous diseases.

PMID- 9244646
TI  - [Implanting of coronary stents in patients with unstable angina].
AB  - In the present study, we retrospectively examined our experience with the Palmaz
      Schatz stent in patients with unstable angina to determine: a) different outcomes
      between patients with stable and unstable angina, b) correlation between the
      class of unstable angina and 1-month and 6-month results, c) correlation between
      lesion morphology and procedural complications. From January 1994 to January
      1996, 160 patients with unstable angina (Group A) and 104 with stable angina
      (Group B) underwent coronary stenting. According to the modified Braunwald
      classification patients with unstable angina were divided into four classes.
      Lesion morphology was classified in simple and complex. Procedural success was
      98% in Group A patients and 99% in Group B patients. We observed 9 (5.6%) major
      complications in Group A vs 2 (1.9%) in Group B. Subacute thrombosis occurred in
      9 patients in Group A and in 2 patients in Group B and these different rates were
      responsible for the higher number of acute myocardial infarction and urgent
      revascularization procedures in Group A patients. At 6-month follow-up there were
      no differences between Group A and Group B patients. Patients in different
      classes of angina showed a similar cardiac event rate at 1-month and 6-month
      follow-up. We found 108 complex lesions in patients with unstable angina vs 20 in
      patients with stable angina (p = 0.0001). Among the 9 patients with unstable
      angina and subacute thrombosis, 6 had a complex lesion and 3 a simple lesion
      (NS). In conclusion, patients with unstable angina receiving intracoronary stent
      have similar clinical outcome at 1-month and 6-month follow-up as compared to
      patients with stable angina. The class of unstable angina and the complex
      morphology of the lesion are not related to procedural complications.

PMID- 9244648
TI  - [Automated color-coded detection of endocardial boundary movements "color
      kinesis"].

PMID- 9244649
TI  - Chaos and predictability: is the universe a game of dice?

PMID- 9244650
TI  - [Etiology of stomach carcinoma--opinions and facts--yesterday and today].
AB  - Recent research demonstrated that views on the etiology of gastric cancer, which
      had been considered true over decades do not correspond with the real situation.
      Therefore, efforts for primary prevention of gastric cancer could not be
      successful. The bacteria Helicobacter pylori is considered today to be an
      important but not the only etiologic factor of this disease. Eradication of this
      bacteria decreases the risk of gastric cancer.

PMID- 9244651
TI  - [Festschrift for Hans Berndt 70th birthday].

PMID- 9244652
TI  - [Home hospital for advanced stage cancer patients: costs and benefits].
AB  - 15,290 patients have been treated in the Bologna home hospital (BHH) until June
      30, 1996. The average daily costs in BHH were estimated as 118789 Liras (ranging
      from 108 569-129027 Lire depending on the nursing category). Care intensity and
      patient's quality of life in the BHH are high. 98% of patients were content with
      the setting in which they were nursed. A questionnaire on the degree of
      satisfaction with the care was completed by 134 BHH patients and 102 patients of
      Division Oncologia Medica. Azienda Ospedaliera Sant, Orsola Malpighi, Bologna.
      Satisfaction with respect to sleeping, meals and family communications was
      expressed more often by BHH patients. Less patients of the BHH evaluated "quality
      of life" reduced or bad (51% vs. 67%) or requested a transfer to the alternative
      setting (03% vs. 47%). Advocating step by step introduction of home care, quality
      of life aspects have priority. Certainly, home care deserves greatest attention
      providing care during the life with cancer. However the final decision about the
      settings of nursing has to be made by the patients themselves in accordance with
      his understanding of quality of life.

PMID- 9244653
TI  - [Molecular etiology of colorectal carcinogenesis, clinical manifestations and
      therapy].
AB  - Mutations of tumor suppressor genes, of the mismatch DNA repair system, and of
      the TGF-beta-II-receptor are the main causes for a higher risk of colorectal
      cancer. Among mutations of the Ape gene, which characterize the clinical
      manifestation of the familial polyposis (FAP), point mutations are dominating
      which create new stop codons or arise from deletions or insertions of nucleotides
      causing frame shifts. Because the binding site of beta-catenin is localized in
      the C-terminus of the Ape protein, disturbances result in the cellular signal
      transfer from its loss. Consequently, the interactions of the usually formed Ape
      beta-catenin complex with the cytoskeleton and the cadherin system in the plasma
      membrane as well as the translocation of beta-catenin into the nucleus cannot be
      realized. Mutations in the genes of the mismatch DNA repair system and of the TGF
      beta-II-receptor, the main defects of the HNPCC (hereditary nonpolyposis
      colorectal cancer), are exclusively identified in sequences of microsatellites.
      Because the majority of Apc gene mutations is also localized in repetitive motifs
      even in CpG islands primary disturbances are to postulate in the methylation
      pattern of the genes producing germline and somatic mutations. Generally,
      complexly connected reactions are involved in this cascade of colorectal cancer
      genesis. This fact explains the relatively late clinical manifestation of the
      disease and offers the possibility to identify carriers with an increased risk of
      colorectal cancer development in order to integrate them into a programme of
      control and preventive medicine. Beside the known treatment by surgery and
      cytostatics, inhibitors of prostaglandin synthesis gain therapeutic significance.
      Cancerogenesis can be efficiently suppressed by inhibition of the COX-2-induction
      (cyclo-oxygenase-2). There is a lack of clinical experience for a decision
      whether a high intraluminal level of butyrate in the large intestine can delay
      colorectal carcinogenesis.

PMID- 9244654
TI  - [40 years breast carcinoma treatment in the Neubrandenburg region.Can an increase
      in prognostically more favorable stages be detected?].
AB  - The data of clinical presentation for women suffering from breast carcinoma were
      analysed for a period of 4 decades retrospectively. The authors have found a
      significant decrease in the duration of the history and an increase of early
      stages of the breast carcinoma. This increase was caused by the introduction of
      mammography. The mammography is the most important method for the diagnosis of
      breast carcinoma in asymptomatic women.

PMID- 9244655
TI  - [Massages--necessary or a luxury?].
AB  - During times of limited funds for medicine, it makes sense to critically
      reconsider commonly used methods for their future application. It is frequently
      demanded in this context to remove the massage from the tariff catalogue of
      health insurances. Therefore, it is attempted to assess the massage on the
      grounds of results to mechanisms of action, indications and contraindications.
      Despite some reservations, this successful method should keep its place by using
      calculated prescription in complex treatment programs.

PMID- 9244656
TI  - [Possibilities of palliative radiotherapy].
AB  - Today, about every second patient with carcinoma is cured, which means on the
      other hand that half of the patients get a metastasis and/or a recurrence. The
      symptoms may be manifold. Physician and patient are looking for a palliative
      treatment. A reliable method is the radiation therapy-especially for brain and
      bone metastases. It should be applied for a short time. The tumor patient has the
      right to be particular about the time being available for him. Most of the
      patients stay rather at home than in the hospital. We undertake the palliative
      radiotherapy preferably in the ambulant setting. The single dose should be high
      and the total dose low. Therefore, a few administrations with greater intervals
      are sufficient. The effect of the palliative radiation therapy extends with
      increase of the single dose. The side effects are minor. In the following, we
      will explain the indications of the palliative/symptomatic radiation therapy.

PMID- 9244657
TI  - [HIV infection and long-term health: therapeutically attainable?].
AB  - New knowledges about the pathogenesis of HIV-induced immune deficiency syndrome
      suggest that a change of the natural history of HIV disease by support with
      antiviral medicaments will be possible. Most important insights are the non
      existence of a viral latency phase and the existence of a strong correlation
      between active viral replication and loss of immunological capacity. Monitoring
      of HIV replication for detection of efficacy of antiviral therapies is necessary.
      Potent combinations of antiviral drugs seem to decrease the tendency for
      development of drug resistant viruses. It seems to be possible to remain healthy
      for a long time by effective drugs.

PMID- 9244658
TI  - [Basic principles and possible variations in combination antihypertensive
      therapy].
AB  - The drug monotherapy of hypertension is successful in about half of the patients.
      The occurrence of relevant side-effects usually leads to a new treatment with an
      antihypertensive drug of another substance category (= sequential monotherapy).
      However, if normotension is not achieved despite good tolerance, the physician
      should combine two antihypertensive drugs with different modes of action. Similar
      to the monotherapy, a treatment procedure individually balanced to the patient
      situation of the circulation, risk factors or coexisting diseases -determines
      success or failure. In the following, useful and clinically reliable combination
      options with first-line substance categories are described. Under the aspects of
      economy, pragmatism, and patient compliance, among other things it is dealt with
      reliable as well as new fixed combination preparations.

PMID- 9244659
TI  - [Anaerobic bacteria as the cause of endogenous infections].
AB  - Most mucocutaneous surfaces of humans harbor a rich indigenous microbial flora
      with predominance of anaerobes. Anaerobic infections are usually endogenous
      indicating that they originate from the host's own flora. Important exceptions
      are botulism, tetanus, food poisoning by Clostridium perfringens, some cases of
      gas gangrene and cases of hospital-acquired C. difficile-induced diarrhea.
      Endogenous anaerobic infections often occur in adjacent to the mucosal surfaces.
      Other organs are infected by penetration or hematogenous spread. A predisposing
      condition to anaerobic infections is a low redox potential resulting from tissue
      destruction, foreign bodies, malignancy or vascular insufficiency. A mixed
      anaerobic-aerobic infection is often found in abscesses or tissue necrosis.
      Antimicrobial therapy must take into account that anaerobic infections are often
      associated with aerobic bacteria.

PMID- 9244660
TI  - [Colonic diverticulitis. Primary clinical and ultrasound diagnosis--report of 47
      cases from general practice].
AB  - Clinical and sonographic diagnosis-Report on 47 cases From 1993 to 1996, 47
      patients with/after acute diverticulitis were examined in our practice by
      abdominal ultrasound. In all 36 cases with acute diverticulitis, a dolent non
      echous wall thickening of descendent/sigmoid colon was seen. In five cases, we
      found other sonographic signs suspicious of penetration. Elevation of CRP and
      sometimes leukocytosis assisted the diagnosis in acute cases. In 39 of the 47
      patients, colonoscopy was performed in the practice mostly during intermissions.
      Diverticula were confirmed in 31 patients whereas sigmoid stenosis from chronic
      diverticulitis could not be passed in 6 cases. 32 patients were treated with
      antibiotics and 10-including those with stenosis-underwent surgery. Except in one
      particular case (tubar abscess involving the sigmoid), operation confirmed
      sonographic findings of severe inflammation (stenosis and sealed perforation,
      respectively, in five cases). In patients presenting with pain in the left lower
      quadrant of the abdomen, colonic diverticulitis has to be considered especially
      if signs of inflammation are present. After clinical examination the first
      diagnostic measures should be venopuncture (CRP, leukocytes) and at the same time
      abdominal ultrasound by an experienced clinician. Due to its high accuracy,
      abdominal ultrasound is sufficient for primary diagnosis and evaluation of the
      course of colonic diverticulitis. Colonoscopy and barium enema follow after
      resolution of acute inflammation.

PMID- 9244661
TI  - [Drug therapy of ulcerative colitis].
AB  - The lethality of the severe ulcerative colitis has been markedly reduced in the
      last decades by drug and surgical therapy. The activity and extent of the disease
      is of immense importance for the drug therapy. In the last 30-40 years numerous
      controlled clinical trials provided treatment options for the active ulcerative
      colitis and maintenance of remission. This paper should give a short overview of
      the standard therapy.

PMID- 9244662
TI  - [Intensification of chemotherapy dosage in metastatic breast carcinoma?].
AB  - During the last decades, improvements in the median survival time in patients
      with metastasized carcinoma of the mamma were hardly achieved. There ist still a
      lack of evidence that the increase in the rate of remissions due to conventional
      chemotherapy leads to an improvement in survival time. In 450 female patients
      with metastasized carcinoma of the mamma, the survival time was analyzed with the
      begin of the metastatic spread in relation to the treatment success of the first
      palliative chemotherapy. The survival time of the responder group was not
      significantly different to the group with a stationary tumor (p = 0.5). As
      patients with primary hormone therapy were included, this result changed if
      patients only with prognostically unfavorable characteristics (high-risk group)
      were selected, which received primarily and exclusively a cytostatic
      chemotherapy. The responder only (partial and complete responder) are profitting
      from the chemotherapy with a significant increase in survival time in comparison
      to the group with a stationary tumor (p = 0.02 and p = 0.006). Therefore, a
      stationary tumor in the high risk group is a result as bad as tumor progression.

PMID- 9244663
TI  - [Selmar Aschheim (1878-1965) and Bernhard Zondek (1891-1966). On the fate of 2
      Jewish physicians and researchers at the Berlin Charite Hospital].
AB  - In 1927, Selmar Aschheim and Bernhard Zondek developed the first biological
      pregnancy test by urine hormone detection. This so-called Aschheim-Zondek
      reaction was a practical application of their research about the effects of
      anteropituitary hormones (gonadotrophin) on the female sexual organs and
      pregnancy. Life and scientific merits of these two gynecologists working in
      Berlin until 1933 are demonstrated. Due to their Jewish extraction, they had to
      leave their duties and finally Germany during National Socialism.

PMID- 9244664
TI  - 9th International/6th European Joint Symposium on Purine and Pyrimidine
      Metabolism in Man. Austria, 1-7 June 1997. Abstracts.

PMID- 9244665
TI  - Current readings in nuclear medicine.

PMID- 9244666
TI  - [HIV: adjusting therapy to viral burden].

PMID- 9244667
TI  - [Protease inhibitors--a class of substances ready to take off].

PMID- 9244668
TI  - [Risk factors in endoscopic manometry for suspected dysfunction of Oddi's
      sphincter].
AB  - OBJECTIVE: An increased incidence of pancreatitis having been reported after
      endoscopic manometry (EM) of the sphincter of Oddi, its incidence and severity as
      well as potential risk factors were investigated prospectively. PATIENTS AND
      METHODS: Between June 1988 and June 1996, standardised manometry was performed in
      207 patients with suspected biliary and 23 with suspected pancreatic sphincter of
      Oddi dysfunction (SOD). All patients had been observed in hospital for at least
      24 hours before the test. The diagnostic criteria of post-manometric pancreatitis
      (PMP) were epigastric pain and a rise in the concentration of serum amylase to at
      least three times normal. Potential risk factors for PMP were elucidated by uni-
      and multivariate analysis. RESULTS: Pancreatitis occurred in 19 patients (9%)
      with suspected biliary and in 6 (26%) with suspected pancreatic SOD (P < 0.01),
      17 of mild and 8 of moderate degree. There were no deaths and no lasting
      sequelae. Previous pancreatitis after endoscopic retrograde
      cholangiopancreatography and the presence of SOD were identified as patient
      associated risk factors (P < 0.01 for each). Method-associated risk factors were
      duration of manometry of more than 5 min (P < 0.05) and manometry in the
      pancreatic duct system (P < 0.05). The risk of pancreatitis was reduced by
      simultaneous endoscopic sphincterotomy for SOD (P < 0.01). CONCLUSION: Specific
      and often avoidable risk factors for postmanometric pancreatitis were identified:
      technical procedure, pancreatitis, SOD. With short duration of manometry,
      avoiding of manometry in the pancreatic duct system and with patient's informed
      consent for simultaneous endoscopic sphincterotomy risk of pancreatitis may be
      lowered.

PMID- 9244669
TI  - [Body composition in type 1 diabetes mellitus. Bio-impedance measurements in 274
      diabetic children, adolescents and young adults].
AB  - BACKGROUND AND OBJECTIVE: Weight gain is a common undesirable side effect of
      insulin treatment in type 1 diabetics. This study tested the assumption that this
      is due to an increase in fat mass. PATIENTS AND METHOD: Bioelectric impedance
      measurements were performed on 157 young male and 117 female diabetics (age 17.6
      +/- 4.9 years; diabetes duration 8.9 +/- 5.7 years) and the fat-free mass (FFM)
      calculated according to the equation of Schfer et al. The data of the diabetics
      were compared with those of healthy controls and normal values published by
      Barlett et al. RESULTS: The average weight of the diabetic cohort was 2.0 +/- 0.7
      kg higher than in the reference groups, adjusted for sex and age. FFM was higher
      by 2.9 +/- 0.7 kg in diabetics than in the healthy cohort of Barlett et al (P <
      0.005), being equally high in males and females (+2.9 +/- 0.7 kg and 2.9 +/- 0.6
      kg, respectively). But compared with the values in metabolically normal controls
      the percentage fat proportion was lower in the diabetics than the controls, but
      not significantly (-1.3 +/- 0.6%). Weight gain was greater in females than males
      (+3.8 +/- 0.9 kg vs +1.2 +/- 0.9 kg, P < 0.05). After correcting for age, there
      was a partial correlation between good metabolic control and FFM in males. The
      form of treatment had no effect on body composition. CONCLUSION: These data
      indicate that weight gain in young diabetics is due not to an increase in fatty
      tissue but in muscle mass. This is probably the result of peripheral
      hyperinsulinism combined with hyperglycaemia.

PMID- 9244670
TI  - [Megaloblastic anemia due to inadequate nutrition].
AB  - HISTORY AND CLINICAL FINDINGS: Over a period of about 6 weeks a 49-year-old woman
      developed increasing exercise-dependent dyspnoea. Her general practitioner had
      diagnosed marked megaloblastic anaemia and she was hospitalised for its further
      elucidation. She reported to have eaten or drunk nothing but sweets, potato
      chips, salty pretzels, lemonade, coffee and tea over the last 2 years. Alcohol
      intake had been reliably denied by her and outsiders. On admission she weighed
      106 kg, her height was 167 cm, and she looked anaemic, had dyspnoea and a sinus
      tachycardia. There was no evidence of external or internal bleeding and the
      physical examination was otherwise unremarkable. INVESTIGATIONS: Laboratory tests
      showed a haemoglobin concentration of 4.7 g/dl, as well as marked folic and
      vitamin B12 deficiency. The food items taken by her contain practically no
      cobalamine and no folic acid. Gastroscopy revealed grade 1 reflux oesophagitis.
      Malabsorption being excluded (normal Schilling test, no demonstrable
      autoantibodies against parietal cells, no evidence of exocrine pancreatic
      insufficiency), the lack of both vitamins and the megaloblastic anaemia caused by
      it could be explained only by a deficient food intake over several years.
      TREATMENT AND COURSE: After administration of cobalamine (1 mg intramuscularly
      twice weekly for 6 weeks, then 300 micrograms daily by mouth for 4 weeks) and
      folic acid (5 mg twice daily for 10 weeks), as well as a well-balanced diet as
      prescribed by a dietician, reticulocyte and erythrocyte concentrations had
      quickly risen to normal at a follow-up examination 2 months later. CONCLUSION:
      The case of an anaemia entirely caused by a deficient diet dearly illustrates the
      need of a well-balanced food intake even in adults.

PMID- 9244671
TI  - [In what way and how intensively should blood pressure be lowered in diabetic
      nephropathy?].

PMID- 9244672
TI  - [Carvedilol].

PMID- 9244673
TI  - [Current status of therapy with bisphosphonates].

PMID- 9244674
TI  - [Quantitative bacteriological and mycological feces analysis].

PMID- 9244675
TI  - [Drug-induced autoimmune disease due to furosemide?].

PMID- 9244676
TI  - [Ebola virus epidemic].

PMID- 9244677
TI  - [What kind of fat on the bread?].

PMID- 9244678
TI  - [Homage to Sulo Toivonen].

PMID- 9244679
TI  - [Lyme borreliosis yesterday, today and tomorrow].

PMID- 9244680
TI  - [Relationship of self-monitoring of blood glucose and HbA1c in diabetic
      patients].

PMID- 9244681
TI  - [Transient hypertrophic cardiomyopathy due to dexamethasone therapy in a
      premature infant].

PMID- 9244682
TI  - [How much alcohol is good for health?].

PMID- 9244683
TI  - [The importance of oral and dental health].

PMID- 9244684
TI  - [Dentistry in the grip of changes].

PMID- 9244685
TI  - [What does a dentist do and why?].

PMID- 9244686
TI  - [Severe acute dental infections].

PMID- 9244687
TI  - [Chronic oral infections--a threat to health?].

PMID- 9244688
TI  - [Saliva as a diagnostic fluid].

PMID- 9244690
TI  - [Role of the dentist in the treatment of cephalalgia and fascialgia].

PMID- 9244689
TI  - [The mouth as a mirror of the body].

PMID- 9244691
TI  - [Should amalgam fillings be replaced?].

PMID- 9244692
TI  - [Why does renal insufficiency progress?].

PMID- 9244693
TI  - [Indications for and problems in active therapy of uremic patients].

PMID- 9244694
TI  - [Hereditary renal diseases and their genetic diagnosis].

PMID- 9244695
TI  - [Recurrent urinary tract infections and their prevention in women].

PMID- 9244696
TI  - [How to manage suspected renal disease].

PMID- 9244697
TI  - [Clinical aspects and diagnosis of nephropathia epidemica].

PMID- 9244698
TI  - [Pathogenesis of glomerulonephritis].

PMID- 9244699
TI  - [IgA nephropathy--the most common form of glomerulonephritis].

PMID- 9244700
TI  - [Vasculitis attacking the kidneys].

PMID- 9244701
TI  - [Diagnosis and therapy of renovascular hypertension].

PMID- 9244702
TI  - [Microalbuminuria in diabetic patients].

PMID- 9244703
TI  - [Acute renal failure in hospitalized patients].

PMID- 9244704
TI  - [Treatment of chronic renal insufficiency].

PMID- 9244705
TI  - [Anemia in chronic renal failure and erythropoietin].

PMID- 9244706
TI  - [Active treatment of renal disease in Finland].

PMID- 9244707
TI  - [Challenges in renal transplantation].

PMID- 9244708
TI  - The enemy within. The role played by immunostimulated macrophages in the
      pathogenesis of insulin dependent diabetes mellitus.

PMID- 9244709
TI  - [Italian cardiology and the Italian Journal of Cardiology: the desire not to cut
      a poor figure].

PMID- 9244710
TI  - [Heart transplantation 1985-1995: 10 years experience at the "Angelo De Gasperis"
      center. Improvement of results by progress in operative criteria].
AB  - BACKGROUND: At 10-years from beginning of transplant experience in our Center we
      analyzed the overall results in an attempt to identify risk factors for early (3
      months) and late (over 3 months) mortality after heart transplantation (HTx).
      METHODS: The data of 313 patients transplanted from November 1985 to June 1995
      were studied and analyzed with a multivariate logistic regression and Cox's
      proportional hazard model. Seventy pre, intra and postoperative variables were
      considered: demographics, clinical status, hemodynamic parameters, donor
      characteristics, donor-recipient mismatch, complications, immunosuppressive
      protocols. In this paper we compared results in patients operated on from 1985 to
      1990 (Group I) and from 1991 to 1995 (Group II) in order to assess improvements
      due to changes in HTx indication and in perioperative treatments. RESULTS:
      Overall mortality in the entire group was 19.8% (62/313): 30-days, 3 months and
      late mortality rates were 8.0%, 10.2%, 10.7% respectively. In Group II mortality
      rates were 7.1%, 8.6% and 2.8% respectively despite significant increase in
      Status I patients (21.5% in Group I vs 40.1% in Group II, p = 0.0008). Main
      causes of early death were: graft failure (46.9%), infection (28.1%), acute-
      rejection (12.5%). Main causes of late death were: cardiac allograft vasculopathy
      (40.0%) and neoplasm (23.3%). The mean follow-up of the 281 survivors more than 3
      months is 45.6 +/- 30.0 months (range 3 to 120 months). Actuarial survival is
      86.9 +/- 1.9%, 78.4 +/- 2.7% and 70.7 +/- 3.9% at 1, 5 and 10 years respectively.
      The difference in the 5-years actuarial survival between Group I and Group II
      patients is statistically significant (70.7 +/- 4.2% vs 84.5 +/- 4.5%, p =
      0.005). TPG (OR 1.19), RAP (OR 1.13) and MD-HD inotropic support of donor (OR
      3.81) were identified as independent risk factors for early mortality. Number of
      moderate rejection at biopsy (OR 1.56) and early postTx infection (OR 3.37) were
      identified as independent risk factors for late mortality. CONCLUSIONS: The
      overall results of our ten-year experience are very satisfying in relation to
      early and late mortality, with a significant favourable trend between patients
      transplanted in the early era (1985-1990) and those transplanted in the recent
      era (1991-1995). The study confirm that morbidity and mortality have the highest
      incidence during the early post-transplantation phase. Pulmonary hypertension and
      elevated preoperative right filling pressure appear to indicate a significantly
      increased risk of early death and only marginally influence late survival that is
      principally related to the severe postoperative complications. Differently from
      other observations, among the donor-related and recipient-donor matching
      variables, this analysis evidenced as significant only the need for MD-HD
      catecolamines during donor-management.

PMID- 9244711
TI  - [Three-dimensional transesophageal echocardiography: a new cardiologic diagnostic
      tool. Initial experience with 150 patients].
AB  - BACKGROUND: Three-dimensional transesophageal echocardiography is a new
      diagnostic tool and its potential has been investigated mainly in international
      centers dealing with research in the field of cardiac pathologies. The clinical
      usefulness and the potential additional information over multiplane
      transesophageal echocardiography in daily clinical practice have not been
      exstensively studied. OBJECTIVES: This study sought to assess the feasibility and
      to define the potential role of three-dimensional technique in a clinical
      cardiology department. POPULATION AND METHODS: One hundred-fifty patients (73
      males, 77 females) aged 17-82 underwent a three-dimensional transesophageal
      echocardiographic study. Indications for the study were the following: 39 mitral
      (26%), 13 aortic (8%) and 4 tricuspidal (2%) valvulopathies, 23 valvular
      prostheses (15%), 6 aortic diseases (4%), 16 sources of embolism (10%), 16
      congenital heart diseases (10%), 14 ischemic heart diseases (9.3%), 14
      cardiomyopathies (9%), 5 other pathologies (3%). The 3 D examination quality was
      graded as insufficient, sufficient and good. The information obtained by "volume
      rendered" and "anyplane" three-dimensional echocardiography were compared with
      the traditional two-dimensional images to determine whether they provided
      additional information. RESULTS: A total of 288 acquisitions were obtained in the
      150 patients (1.9 acquisitions per patient). Examinations were graded of good
      quality in 99 patients (61%), sufficient in 36 (24%) and insufficient in 15
      patients (10%). Additional informations were obtained in 33 patients (22%) by
      "volume rendered" echocardiography and by "anyplane echocardiography", including
      mitral regurgitation or repair for valvular prolapse (11 patients), aortic valve
      malformations and endocarditis (4 patients), congenital heart diseases (9
      patients), right ventricular dysplasia (6 patients) or hypertrophic
      cardiomyopathy (1 patient), tricuspid regurgitation (2 patients). The additional
      information were obtained in patients in the group of good 3 D reconstructions
      quality in all but two cases. CONCLUSIONS: The diagnostic use of the
      transesophageal technique with 3 D facilities permitted to obtain an overall 22%
      of additional information. These results will stimulate further study to evaluate
      the advantages of the three-dimensional technique in specific clinical fields of
      application.

PMID- 9244712
TI  - [Inferior infarct with associated anterior ST elevation: an unusual presentation
      of right ventricular involvement. Description of three cases and a brief review
      of the problem].
AB  - ST segment elevation in the left precordial leads in the setting of an acute
      inferior myocardial infarction may represent an unusual electrocardiographic
      pattern of right ventricular infarction. We present our experience about three
      patients with first inferior acute myocardial infarction in whom concomitant
      anterior ST segment elevation was observed. All patients were submitted to urgent
      coronary angiography because of repeated episodes of myocardial ischemia (case 1)
      or hemodynamic derangement (case 2, 3) with hypokinetic arrhythmias (case 3). In
      all patients 2D echocardiographic examination performed before angiography showed
      a dilated, hypo-akinetic right ventricle and wall motion abnormalities only in
      inferior, posterior and/or lateral segments of the left ventricle. Proximal right
      coronary occlusion was found in all patients, and coronary angioplasty was
      successfully attempted in all but one case. In patients with first inferior
      myocardial infarction, left precordial ST segment elevation mimicking an anterior
      infarction may be the less frequent ECG pattern of right ventricle ischemic
      involvement. Routine right chest leads and early echocardiographic examination
      allow to identify the patients with right ventricle infarction and concomitant
      anterior ST segment elevation. In these patients, early and correct diagnosis is
      important in order to choice the appropriate therapeutic pathway.

PMID- 9244714
TI  - [The periodic flashes of E. Brunwald: lowering cholesterol levels in subjects
      with myocardial infarction and normal cholesterol levels].

PMID- 9244713
TI  - [Massive pulmonary embolism during the third trimester of pregnancy:
      effectiveness of thrombolytic treatment with alteplase].
AB  - The authors report on a 33-year old woman with massive, life-threatening
      pulmonary embolism at the third trimester of pregnancy. The diagnosis was rapidly
      accomplished in the Emergency Department by two dimensional-Doppler
      echocardiography that showed signs of pulmonary hypertension as well as a large,
      floating thromboembolus in the right atrium. As the hemodynamic deterioration
      persisted after treatment with iv heparin, the patient received alteplase 50 mg
      as a bolus over 5 minutes. About 30 minutes later, a further 50 mg infusion of
      alteplase was given over 60 minutes because clinical conditions were
      progressively worsening. After an alteplase dose of 75 mg, the woman showed a
      definite improvement in clinical-hemodynamic status and echocardiography
      documented a reduction of right ventricular overload and atrial clot
      disappearance. Two hours later the patient was submitted to cesarean section,
      because of the onset of uterine contractions, and delivered a vital baby. The
      occurrence of uterine bleeding was antagonized by the infusion of fresh-frozen
      plasma and a moderate anemia was subsequently treated with iron preparations. The
      mother and her baby were discharged on 16th day in fairly good general
      conditions. The authors emphasize the leading role of early echocardiography in
      the clinical decision making and the lifesaving potential of full dose
      thrombolytic therapy without serious adverse effects.

PMID- 9244715
TI  - [The choice between primary angioplasty and thrombolysis: is there any change
      after GUSTO-IIb?].

PMID- 9244716
TI  - [Replacement of the aortic valve with a pulmonary autograft: experience at the
      University of Verona].
AB  - BACKGROUND: Early and long term results after surgical replacement of the aortic
      valve depend to a large degree on the type of valve substitute used. Pulmonary
      autograft offers many theoretical advantages, particularly in young patients.
      METHODS: Between July 1994 and August 1996, 15 patients (12 male) with a mean age
      of 28 +/- 6 years (range 14 to 36 years) were selected for aortic valve
      replacement with a pulmonary autograft. The aortic valve disease was isolated
      insufficiency in 7 cases (47%), stenosis in 3 (20%) and mixed lesion in 5 (33%).
      One patient in the last group had bacterial endocarditis (Streptococcus mitis).
      Seven patients (47%) had a bicuspid aortic valve. In 3 cases (20%) the autograft
      was inserted as a scalloped subcoronary implant. Twelve patients (80%) had total
      aortic root replacement with re-implantation of the coronary ostia. The right
      ventricular outflow tract was reconstructed with a cryopreserved homograft (13
      pulmonary; 2 aortic). The aortic cross-clamp time was 156 +/- 18 minutes with a
      total bypass time of 221 +/- 26 minutes. RESULTS: All patients survived the
      operation. Three postoperative bleeding (20%) necessitated re-exploration. Mean
      post-operative hospital stay was 10 +/- 2 days. All patients were discharged on
      aspirin for the period of three months. One patient (7%) with moderate neo-aortic
      valve insufficiency died suddenly 11 months post-operatively. All survivors are
      asymptomatic, in NYHA FC 1 at a mean follow-up time of 15.7 months. Freedom from
      reoperation, valve related complication and endocarditis is 100%. Two-dimensional
      (2-D) echocardiography six months postoperatively showed a mean left ventricular
      outflow gradient of 13 +/- 4 mmHg with no evidence of aortic regurgitation in 11
      cases (78.5%) and trivial in 3 (21.5%). CONCLUSIONS: Although the Ross operation
      is technically more challenging and requires a longer operating time than
      standard procedures, this does not seem to affect early mortality and morbidity.
      Clinical and haemodynamic results appear to be gratifying. Continued patients
      evaluation particularly with regard to evidence of valve degeneration and
      arrhythmias in the long term is warranted.

PMID- 9244717
TI  - [Research for the "ideal" aortic valve substitute].

PMID- 9244718
TI  - [Comparison of anti-arrhythmic therapy guided by the transesophageal
      electropharmacologic test and emperic therapy in the prophylaxis of atrial
      fibrillation recurrence].
AB  - BACKGROUND: There is no written data about the efficacy of transesophageal
      electropharmacologic test (TEPT) to guide antiarrhythmic therapy in the
      prophylaxis of paroxysmal atrial fibrillation (PAF) recurrences. Aim of this
      study was to assess the efficacy of TEPT compared to empiric treatment in the
      prophylaxis of PAF. METHODS: One-hundred-sixty patients (pts) with previous
      episodes of PAF were randomized in two groups: Gr A (90 pts) was submitted to
      basal transesophageal electrophysiologic study (BTES); Gr B (70 pts) was
      submitted to randomized empiric antiarrhythmic therapy with flecainide (F),
      propafenone (P) and sotalol (S). The end-points of stimulation protocol in Gr A
      were the induction of sustained atrial fibrillation (SAF)- > or = 1 min duration-
      or the end of protocol. SAF was inducible in 68/90 pts (Gr A1) while it was not
      in 22/90 pts (Gr A2). Pts in Gr A1 were subsequently submitted to TEPT at steady
      state of F, P or S randomized in first choice. Pts responders (R) (SAF non
      inducible) were submitted to TEPT with other antiarrhythmic drugs randomized in
      second choice: R were followed-up with the same drug in chronic oral assumption,
      while non responders (NR) were submitted to TEPT with the last drug and followed
      up with the same drug both in R and NR case. The same stimulation protocol was
      employed in TEPT as in BTES. Pts in Gr A2 withdrew from the study. During follow
      up all-pts were submitted to periodic specialist examinations every three months.
      In case of PAF recurrence pts withdrew from the study. RESULTS: Mean follow-up
      duration in the study population was 17.5 +/- 8.5 months. One-hundred-eight TEPT
      were performed in Gr A1: 36 tests with F, 40 with P and 32 with S. Twenty pts
      were R with F (55% of tests) and 17 finished the follow-up, 22 pts were R with P
      (55% of tests) and 16 finished the follow-up, 19 pts were R with S (59% of tests)
      and 15 finished the follow-up; 3 pts with F, 2 pts with P and 2 pts with S were
      NR in last choice and finished the follow-up. In Gr A1 61/68 pts (90%) were R and
      55/68 (81%) finished the follow-up (13 pts withdrew from the study). In Gr B (70
      pts) 23 pts were randomized to F and 20 finished the follow-up, 24 pts were
      randomized to P and 20 finished the follow-up, 23 pts were randomized to S and 20
      finished the follow-up (10 pts withdrew from the study). PAF recurrences during
      follow-up in Gr A1 were in 15/55 pts (27%): 9/48 pts (19%) R and 6/7 pts (86%)
      NR, and in Gr B in 41/60 pts (68%). Gr A1 vs Gr B p < 0.001. Univariate and
      multivariate statistical analysis showed the empiric treatment as the only
      variable with high predictive value for PAF recurrences (risk ratio 1.53). PPV
      and NPV of TEPT were respectively 86 and 81%. CONCLUSIONS: TEPT-guided
      antiarrhythmic therapy in the prophylaxis of PAF recurrences seems to be an
      effective method in predicting the efficacy of the chronic antiarrhythmic
      therapy, when compared to the empiric treatment. The non inducibility of SAF at
      TEPT would have a high predictive value for event-free follow-up.

PMID- 9244719
TI  - [A case of cholesterol crystal embolism following coronarography: a
      contraindication of the procedure?].
AB  - Authors report on one patient with cholesterol embolization following cardiac
      catheterization and coronary by-pass surgery. During the immediate post-operative
      period, neurological and renal complications occurred because of recurrent
      cholesterol embolization. One month after surgery the patient died from a sudden
      neurological coma. Cholesterol crystal embolization appears to be a contra
      indication to heart surgery, even in a strongly symptomatic patient, when the
      spontaneous course of the existing cardiac disease is not life-threatening in the
      short term.

PMID- 9244720
TI  - [Omniplane transesophageal echocardiography: an improvement in the monitoring of
      percutaneous pulmonary valvuloplasty].
AB  - A 16 year old girl underwent percutaneous balloon dilation of the pulmonary
      valve. The procedure was carried out in the catheterization laboratory under
      transesophageal echocardiographic guidance with the patient anesthetized
      (ketamine) without endotracheal intubation. A 64 elements phased array
      "omniplane" TEE probe connected to a Sonos 1500 Hewlett-Packard system was used.
      The transducer assembly encased within the tip of the endoscope can be rotated
      through a 180 degrees arc counterclockwise and clockwise, thus obtaining a
      multitude of imaging planes. The right ventricular outflow tract and pulmonary
      valve could be visualized very well and therefore monitored accurately during all
      phases of the procedure. In the future this technique will be able to reduce the
      need for X-ray exposure and dye injection during percutaneous pulmonary
      valvuloplasty especially in cases in which their use could be contraindicated.

PMID- 9244721
TI  - [Clinical and instrumental indicators of chronic heart failure: do we know how to
      use them?].

PMID- 9244722
TI  - [Apical hypertrophic cardiomyopathy: morphologic characterization, functional and
      clinical aspects].

PMID- 9244724
TI  - [A bibliometric instrument and the achievement of a goal].

PMID- 9244723
TI  - [Low energy endocavitary cardioversion in atrial fibrillation: effectiveness,
      safety, tolerability and future prospects].

PMID- 9244726
TI  - [The psychological side of chronic heart failure. A pluriannual experience].
AB  - The present study summarizes the authors' experience reached in the last four
      years with chronic heart failure patients', particularly referring to the
      psychological aspects. The 218 male patients (age 51.7 +/- 8.3) psychological
      profile (obtained by means of the CBA 2.0 Primary Scales) has shown higher scores
      in the anxiety, depression and psychophysiological disorders scales and lower
      scores in some of the fear scales, compared with the reference normative group.
      The CBA 2.0 Schedule 4 has enlightened suicidal ideas, eating and sleep
      disorders, economic and sexual problems. The comparison between the psychological
      and the many cardiological variables taken into account, has not allowed to
      highlight significant relationships on the whole. Our data support the necessity
      to introduce other--likely subjective--variables in the studies aimed at
      analyzing the relationships between psychological and cardiological factors in
      the chronic heart failure patients.

PMID- 9244725
TI  - [Hemorrhagic complications of oral anticoagulant therapy: results of a
      prospective multicenter study ISCOAT (Italian Study on Complications of Oral
      Anticoagulant Therapy)].
AB  - BACKGROUND: To assess the incidence of bleeding complications during oral
      anticoagulant therapy (OAT) in a population of patients representative of daily
      practice in Italian anticoagulation clinics. METHODS:  DESIGN: prospective,
      inception-cohort, multicentre. SETTING: Thirty-four anticoagulation clinics
      federated in the Italian Federation of Anticoagulation Clinics. PATIENTS: 2745
      consecutive patients, included from beginning of their first OAT course. Most
      patients were aged between 60 and 79 y (57.8%), with 8% being > or = 80 y. Venous
      thromboembolism was the most frequent indication for OAT (one third of all the
      patients), followed by non ischemic heart disease which mainly included atrial
      fibrillation (16.8% of patients). Warfarin (in 63.8% of patients) and
      acenocoumarol were the only anticoagulant drugs used. The targeted
      anticoagulation intensity was low (INR < or = 2.8) in 71% of patients and high
      (INR > 2.8) in the remainder. OUTCOMES: Fatal, major and minor bleeding events.
      Thrombotic events were also recorded, though not analyzed in the present report.
      FINDINGS: During the 2011 patient-years (pt-y) of follow-up, 153 bleeding
      complications (7.6% pt-y) were recorded--5 fatal (all cerebral haemorrhages,
      0.25% pt-y), 23 major (1.1% pt-y) and 125 minor (6.2% pt-y). The rate of events
      did not vary according to sex, coumarin type, size of enrolling centre or
      targeted therapeutic range; it was higher in older patients (10.5% pt-y in those
      aged > or = 70 y, relative risk--RR--1.75, p < 0.001), in cases where indication
      for anti-coagulant treatment was peripheral and/or cerebrovascular disease (12.5%
      pt-y; RR 1.80, p < 0.01) and during the first 90 days of treatment (11% pt-y, RR
      1.75, p < 0.001). One fifth of bleeding events occurred at a very low
      anticoagulation intensity (INR < 2; the category rate being 7.7% pt-y); the rate
      was 4.8% pt-y in the 2.0-2.9 INR category, reaching 9.5% pt-y, 40.5% pt-y and
      200% pt-y in the 3-4.4, 4.5-6.9 and > or = 7 INR categories respectively (RR for
      INR levels > 4.5 = 7.91, p < 0.0001). CONCLUSIONS: The overall rate of bleeding
      events recorded in the present study was much lower than that recorded in other
      (including recent) observational and experimental studies. The risk of bleeding
      increased in the following cases: age > 70 y; arterial vascular disease as
      indication for OAT; first 3 months of treatment; INR values > or = 4.5. OAT has
      become safer in recent years, particularly if monitored in special
      anticoagulation clinics. Caution should be exercised when prescribing OAT in
      elderly patients and the intensity anticoagulation levels should be closely
      monitored to minimize incidental periods of overanticoagulation.

PMID- 9244727
TI  - [The exercise test with atropine].
AB  - BACKGROUND: Exercise testing remains the most accessible and widely used
      technique for the detection of coronary artery disease (CAD) and for the
      assessment of its severity. Clinical usefulness of the simple exercise test is
      limited by poor sensitivity and imperfect specificity. Many patients referred for
      diagnostic stress testing cannot achieve an adequate increase in heart rate due
      to lack of motivation, poor physical condition, or medications. Atropine
      increases the heart rate and therefore myocardial oxygen consumption, and might
      improve the diagnostic accuracy of exercise testing, either reducing the number
      of non-diagnostic examinations, or increasing the positivity of the test in
      patients with non severe coronary disease. METHODS: One-hundred-seventy-two
      consecutive patients (144 males and 28 females, age 58 +/- 8 years) with
      suspected coronary artery disease underwent exercise testing and coronary
      angiography. Exercise testing was considered positive in the presence of ST
      segment depression > or = 0.10 mV horizontal or downsloping, > or = 0.15 mV
      upsloping, or in the presence of ST elevation without Q waves. The test was
      considered negative in the absence of significant ST depression or elevation if
      the exercise heart rate was > 85% of age-predicted maximum, non-diagnostic if the
      heart rate was < 85%. In 148 patients (86%) coronary angiography showed CAD (>
      70% luminal reduction in at least one major vessel), in 24 patients (14%) non
      significant CAD or angiographically normal coronary arteries (NoCAD). Exercise
      testing was positive in 134 patients (78%: 85% in CAD, 33% in NoCAD), negative in
      13 patients (8%: 3% in CAD, 38% in NoCAD), non-diagnostic in 25 patients (14%;
      12% in CAD, 29% in NoCAD). The sensitivity was 85%, specificity was 38%, and
      diagnostic accuracy 78%. In the 25 patients with non-diagnostic test (18 CAD, 7
      NoCAD) the exercise was repeated 30-90 minutes later, immediately after i.v.
      injection of 1-2 mg of atropine, and was stopped at the same workload of the
      index test. RESULTS: The atropine-exercise test was well tolerated and
      accomplished in all cases. The maximal heart rate (139 +/- 11 vs 121 +/- 11) and
      the double product (25,308 +/- 4082 vs 22,166 +/- 3569) were significantly
      greater after atropine. The increase of the maximal heart rate improved the
      detection of the electrocardiographic signs of exercise-induced myocardial
      ischemia only in CAD patients. In the 18 CAD patients the atropine-exercise test
      was positive in 8, negative in 5, non-diagnostic in 5. In the 7 NoCAD patients
      the atropine-exercise test was positive in 1, negative in 6. The test remained
      non-diagnostic only in 3% of patients. The sensitivity of the test with atropine
      was 91%, specificity was 63%, and diagnostic accuracy 87%. CONCLUSIONS: The
      addition of atropine to exercise testing, which causes further chronotropic
      stress to the myocardium, is well tolerated and safe, and improves the diagnostic
      accuracy of the test for the detection of coronary artery disease in patients who
      cannot achieve an adequate exercise heart rate. The combination with atropine
      increases the utility and the cost-effectiveness of exercise testing.

PMID- 9244728
TI  - [Heart transplant over 55 years].
AB  - BACKGROUND: The age of recipient has been thought for several years to be one of
      the most important predictors of survival after heart transplantation. Therefore
      patients older than age 50 years were usually excluded from heart
      transplantation. The marked improvement in survival after clinical introduction
      of cyclosporine made a critical revision of selection criteria for heart
      recipients. In this article we retrospectively analyze the outcome of heart
      transplantation dividing the patients into two groups: Group A < or = 55 years,
      Group B > 55 years respectively. METHODS: We analyzed 437 patients who underwent
      heart transplantation, immunosuppressive protocol for all the patients was
      cyclosporine, azathioprine and prednisone. Group A included 284 patients, Group B
      153 patients. We studied demographic, clinical and haemodynamic data pre- and
      post-operatory in both groups. RESULTS: In Group A was more frequent dilated
      cardiomyopathy (p < 0.01) and the patients arrived at heart transplantation in
      worse haemodynamic conditions requiring more frequently inotropic infusion and/or
      mechanical support (intraaortic balloon pump, left ventricular assist device).
      Post-operatory course was more complicated in Group B patients where ischemic
      cardiomyopathy was more frequent (p < 0.001); intensive care stay, inotropic
      drugs infusion, mechanical ventilation and hospital mortality were higher in
      Group B, although non significantly. The donor age was significantly higher in
      Group B (p < 0.001), anyway the statistical analysis did not show a correlation
      between donor age and more complicated post-operative course. Follow-up did not
      show significative differences in the two groups considering haemodynamic data,
      metabolic disorders, graft coronary disease, infection and rejection rates. On
      Group B is significantly higher tumor incidence (p < 0.05) and peripheral
      vascular complications (p < 0.01). Actuarial survival at 5 and 7 years is
      respectively in Group A 80.3 and 72.9%, in Group B 75.4 and 71% (p = ns).
      CONCLUSIONS: Heart transplantation in patients older than 55 years with end-stage
      heart disease is a valid therapeutic option with excellent long-term survival;
      pre-operative screening must be particularly accurate and older donors should be
      considered.

PMID- 9244729
TI  - [Electrophysiologic characteristics of the atrium during chronic atrial
      fibrillation in man].
AB  - AIM OF THE STUDY: To evaluate the electrophysiologic characteristics of human
      atria during chronic atrial fibrillation. METHODS: The study was performed in 24
      patients who underwent low energy intracardiac atrial cardioversion for chronic
      atrial fibrillation before the procedure itself. No patients have been assuming
      antiarrhythmic drugs for a period of at least 5 half-lives of the drug. In 10
      patients the possibility of local capture in several atrial sites (7 tested) by
      means of high-rate atrial pacing was evaluated. A Franz catheter for recording of
      monophasic action potential (MAP) and for atrial stimulation was positioned in
      the right atrium at a distance of 1 cm from a quadripolar catheter which was also
      positioned for the recording of the bipolar electrogram by the distal and
      proximal pairs and of the unipolar electrogram by the distal electrode. A
      decapolar catheter for shock delivery was positioned in the coronary sinus as
      well. In the remaining 14 patients an additional quadripolar catheter for His
      recording was positioned but atrial stimulation was not performed. Furthermore,
      recordings of the bipolar and unipolar electrograms were obtained in several
      sites and the correlation between MAP and bipolar electrogram morphology was
      evaluated. The existence of a difference in fibrillation cycle-length in
      different sites suggestive of a dispersion of refractory periods was also
      screened. Wells' and Waldo's classification was used for bipolar electrograms
      whereas MAP was classified into type 1 (regular), type 2 (partially irregular),
      and type 3 (totally irregular). RESULTS: In 10 patients submitted to atrial
      stimulation, local capture was obtained in 37 out of 43 stimulation sites (86%).
      Local capture was more frequently obtained in the lateral wall than in other
      sites (p < 0.05). The capture was obtained only in type 1 and type 2 atrial
      fibrillation. In the remaining 14 patients a perfect correlation (100%) between
      type 1 and 3 atrial fibrillation and type 1 and 3 MAP respectively was observed.
      In type 2 atrial fibrillation the correspondence was lower (67%). Fibrillation
      cycle-length contemporary recorded in the 6 different atrial sites were
      significantly different in 8 patients out of 12 (67%) in whom a stable recording
      could be obtained in basal conditions. CONCLUSIONS: 1) In chronic atrial
      fibrillation an excitable gap allowing local capture is present in the majority
      of patients and in most atrial sites, at least in the right atrium. 2) The
      morphology of bipolar and MAP recordings are fairly correlated and they reflect
      the complexity and the degree of synchronization of the arrhythmia. 3) A
      dispersion of refractoriness seems to contribute to the maintainance of the
      arrhythmia.

PMID- 9244730
TI  - [Anaphylactoid reaction during administration of tissue plasminogen activator (t
      PA)].
AB  - The use of tissue plasminogen activator (t-PA) in the management of acute
      myocardial infarction, as effective thrombolytic agent, is well established.
      Thrombolytic therapy, limiting the extent of myocardial necrosis, reduces the
      infarct-related morbidity and mortality and improves the prognosis in patients
      with acute myocardial infarction. Thrombolytic agents present various side
      effects. Allergic reactions may occur with both streptokinase (ST) (or with
      anistreplase, the equimolecular mixture of streptokinase and human plasminogen);
      and t-PA. The incidence of allergic reactions associated with the use of t-PA is
      much lower if compared with other thrombolytic agents. Since t-PA is structurally
      identical to endogenous t-PA, its administration should not cause anaphylactic
      reactions. The purpose of this case presentation is to describe the occurrence of
      an anaphylactoid reaction during infusion of t-PA in a 63 year-old man, admitted
      to the Cardiac Care Unit (C.C.U.) with diagnosis of acute myocardial infarction.

PMID- 9244732
TI  - [Mechanisms of ischemic preconditioning: relation with ischemia-reperfusion
      injury].
AB  - If a coronary occlusion long enough to produce a myocardial infarction is
      preceded by one or more brief periods of occlusion, the infarct size is reduced
      with respect to the area at risk. Also the ischaemia reperfusion injury is
      remarkably reduced. Such effects form the ischaemic preconditioning. Ischaemia
      reperfusion injury is attributed to a Ca2+ overload of the myocardial fibres
      together with an inadequate resynthesis of ATP, a loss of membrane phospholipids
      and a release of free oxygen radicals. The inadequate resynthesis of ATP is
      responsible for an increased concentration of nucleosides and purinic bases with
      swelling of the myocardial fibres. The cell Ca2+ overload depends on a reduced
      activity of the ionic pumps caused by the oxygen lack during ischaemia. During
      reperfusion the vascular endothelial cells of the previously ischaemic area
      release free oxygen radicals in response to the activity of the xanthine-oxidase
      on hypoxanthine produced by the ischaemic myocardium. This initial release of
      oxygen radicals is responsible for the adhesion of neutrophils to the
      endothelium. After adhesion also the neutrophils release free radicals due to the
      activity of NADPH-oxidase on molecular oxygen. Myocardial, neural and endothelial
      mechanisms account for the protective effect of preconditioning. Myocardial
      mechanisms include the release of adenosine as well as of antioxidant enzymes.
      Adenosine, which activates protein-kinase C, favours the phosphorylation of a
      protective protein, whereas the antioxidant enzymes impair the activity of the
      free oxygen radicals. Preconditioning may also involve the synthesis of a heat
      shock protein. Neural mechanisms are represented by a reduced release of
      noradrenaline from the sympathetic nerve endings and a reduced sensitivity of
      myocardium to noradrenaline. Finally, vascular endothelial cells take part in
      preconditioning by means of an increased production of nitric oxide which seems
      to exert a protection against arrhythmias.

PMID- 9244731
TI  - [Unidirectional block and longitudinal dissociation in an accessory pathway
      induced by radiofrequency].
AB  - This report describes an unusual arrhythmia due to partial damage of an accessory
      pathway by radiofrequency energy delivered during a catheter ablation procedure.
      The following phenomena were observed after the first radiofrequency current
      application: a) manifest anterograde conduction over the Kent bundle was
      abolished, so that preexcitation disappeared; b) concealed anterograde conduction
      over the accessory pathway was interrupted, resulting in initiation of
      orthodromic re-entrant tachycardia by any sinus impulse; c) retrograde conduction
      through the accessory pathway was impaired, but still present, and a pattern of
      longitudinal dissociation manifested; this was suggested by alternation of the R
      P intervals, that during orthodromic tachycardia were alternatively long and
      short. Following a second radiofrequency application, the R-P interval during
      orthodromic tachycardia became markedly prolonged (0.36 sec), to the extent that
      the pattern mimicked a form of atrial or sinus tachycardia. Retrograde accessory
      pathway conduction was totally interrupted following a third radiofrequency
      energy application.

PMID- 9244733
TI  - [One hundred years of heart surgery. In memory of Guido Farina].

PMID- 9244734
TI  - Coronary angioplasty 1997: twenty years after.

PMID- 9244735
TI  - [Citizens--National Health Service-Doctors: relationships to be renewed].

PMID- 9244736
TI  - [To stent or not stent, the question and the problem].

PMID- 9244737
TI  - [Indications for heart transplant: retrospective evaluation of criteria for
      selection of candidates].
AB  - INTRODUCTION: Heart transplantation (HT) is a largerly accepted therapy for
      patients with refractory congestive heart failure. However, lack of donors
      imposes a rigorous choice among candidates for transplantation. Aim of this study
      was to identify retrospectively determinants for the selection of recipients.
      METHODS: Between december 1985 and december 1993 500 patients were listed for HT
      at the Department of Cardiovascular Surgery of the Padua University. Among United
      Network for Organ Sharing (UNOS) status II patients, 42 transplanted (group I)
      and 38 died waiting for a donor (group II) were chosen. The following parameters
      were collected at the time of insertion into the waiting list: sex, blood group,
      diagnosis, age, body surface area, natriemia, renal function, hepatic function,
      presence of ventricular arrhythmias, use of ACE-inhibitors, cardiac index, mean
      pulmonary pressure, mean wedge pressure, mean arterial pressure, central venous
      pressure, pulmonary arteriolar resistances, left ventricular ejection fraction.
      Also the time on waiting list until a final event (transplantation or death) was
      considered. RESULTS: Comparing the two groups the diagnosis of dilated
      cardiomyopathy (59.4% group I vs 36.8% group II; p = 0.04) and ejection fraction
      (26.4 +/- 9.1% group I vs 22.2 +/- 8.0% group II; p = 0.03) were the only
      variables statistically different. Multivaried analysis evidenced some parameters
      as independent predictors for HT. In detail, being listed for HT for more than 6
      months lowered the probability to receive a heart to 0.34, while waiting for more
      than 12 months increased it to 2.64. Mean arterial pressure higher than 75 mmHg
      increased the probability for HT to 2.87, while an increase in mean pulmonary
      pressure of 5 mmHg lowered the probability to 0.80. An increase in the cardiac
      index of 0.5 l/m1/m2 lowered the probability to 0.61. A blood group other than 0
      increased the possibility to 3.60, the basal surface area higher than 1.78 m2
      lowered it to 0.306 and an ejection fraction higher than 22% increased it to
      3.94. CONCLUSIONS: We can conclude that parameters which predict the outcome of
      patients listed for HT were not only size matching, blood group and waiting time,
      but also ejection fraction, arterial pressure and diagnosis.

PMID- 9244738
TI  - [Brain death: myocardial consequences, an experimental study on pigs].
AB  - It is well known that brain death is responsible for major problems encountered
      in the clinical setting that may alter heart graft viability before
      transplantation. To investigate these myocardial dysfunctions, a model of brain
      death was prepared in pigs. Anaesthetised pigs were ventilated with FiO2 of 50%
      through an endotracheal tube. Animals were monitored by measuring systemic
      arterial pressure, pulmonary artery pressure, cardiac output, left ventricular
      developed pressure and dP/dT (Millar probe), cardiac contractility
      (sonomicrometers crystals), ECG, myocardial tissue oedema (impedance
      spectroscopy) and heart rate. Blood samples were drawn to assess arterial blood
      gases, serum electrolytes, plasma catecholamine levels, LDH isoenzymes and
      ascorbil free radicals production. Myocardial high energy contents (adenosine
      triphosphate, creatine phosphate) were measured by spectroscopy MRI. After 30
      minutes stabilisation, brain death was induced by ligation of the supra-aortic
      vessels. To assess myocardial impairment all the parameters mentioned were
      recorded at baseline, 1', 30', 60', 120' and 180' following the brain death.
      Results showed initial tachycardia and a significant increase (p < 0.05) in
      cardiac function at 1' and 30', related to the cathecolamine level variations,
      followed by a significant depression (p < 0.05) of cardiac contractility by the
      end of the third hour; there was no modification whatsoever of myocardial high
      energy contents and of ascorbil free radical and LDH isoenzymes productions. In
      this pig model of brain death the observed myocardial dysfunction was directly
      related to the induced catecholamine secretion without any myocardial high energy
      substrate depletion up until 180'. Such results could be taken into account when
      evaluating a donor heart, allowing to use organs judged nowadays not feasible,
      and could be of some help in lowering the number of the "defaillances" of the
      transplanted hearts.

PMID- 9244740
TI  - [Percutaneous mitral valvuloplasty in mitral restinosis after surgical
      commissurotomy].
AB  - The frequency of mitral restenosis after surgical commissurotomy has been
      estimated between 10 and 30% up to 10 years and 85% up to 28 years. Aim of this
      study was to analyze the results of balloon mitral valvuloplasty (BMV) in a
      series of patients with previous surgical commissurotomy. METHODS: Between
      December 1988 and December 1995 432 patients underwent BMV. Of these patients, 30
      (6.9%; 10 men, 20 women, aged 53 +/- 12 years) had recurrent mitral stenosis
      after surgical commissurotomy. Contraindications to BMV were the evidence of left
      atrial thrombi at transesophageal echocardiography and/or of mitral insufficiency
      > 2+/4+. The Inoue's single balloon catheter was used for all the procedures.
      RESULTS: BMV resulted in a decrease in mean mitral gradient from 12.6 +/- 3.8 to
      6.1 +/- 2.9 mmHg, and an increase in mitral valve area from 1.03 +/- 0.19 cm2 to
      1.95 +/- 0.40 cm2. A mitral insufficiency > or = 3+/4+ occurred in 4/30 BMV
      (13%). At follow-up (mean 27 +/- 18 months) 20/26 patients (77%) remained
      clinically improved: 54% were in NYHA class I and 23% in class II. CONCLUSIONS:
      BMV is an effective short- and long-term procedure for patients with previous
      surgical commissurotomy, with a low additional risk of complications. Thus, BMV
      can be considered the treatment of choice in these patients.

PMID- 9244739
TI  - [Mid-term clinical condition and prognosis in adrenergic ventricular tachycardia
      in children with apparently normal hearts].
AB  - INTRODUCTION: Ventricular tachycardia is the most common diagnosis among children
      with exercise or emotion-related syncope. The aim of the study was to assess the
      prognosis and the clinical course of children, without long QT syndrome, with
      exercise-related ventricular tachycardia and apparently normal heart. METHODS:
      Since January 1984, we studied 14 children (mean age 9.7 +/- 3.8 years) with
      exercise-related ventricular tachycardia, and, at the initial detection, without
      demonstrable heart disease, as assessed by clinical evaluation, electrocardiogram
      and mono-bidimensional echocardiogram. Six patients had exercise related syncope,
      1 exercise intolerance and 7 were asymptomatic. All patients underwent exercise
      testing on treadmill and 24-hour ECG monitoring. All patients were treated with
      antiarrhythmic drugs. All patients were tested by exercise testing and 24 hour
      ECG monitoring, alternatively, every six months, during therapy or after complete
      wash-out of the drug used. RESULTS: Ventricular tachycardia, detected by exercise
      testing and Holter monitoring, was polymorphic in 4 symptomatic patients,
      monomorphic with left bundle branch block morphology and inferior axis in the
      others. The mean rate of monomorphic ventricular tachycardia was 224 +/- 35 bpm
      in the symptomatic children and 180 +/- 33 bpm in the others (p = 0.03).
      Successful chronic treatment was achieved with beta-blockers in 5 cases,
      propafenone in 6, sotalol in 2 and flecainide plus metoprolol in 1. During follow
      up (6 +/- 2.7 years), 1 patient with polymorphic ventricular tachycardia, on
      therapy, suddenly died during exercise, the other symptomatic patients had no
      variation of their arrhythmia on routine tests, except 1 who, after propafenone
      was stopped, had ventricular fibrillation during exercise testing. Among the 7
      asymptomatic patients, 5 had no evidence of ventricular tachycardia on routine
      test after 2 +/- 3 years; the others had no variation of their treatment.
      CONCLUSION: Exercise related ventricular tachycardia in children seems: 1) to
      have more severe prognosis if symptomatic or polymorphic; 2) mostly to arise from
      right ventricle; 3) to be successfully treated by antiarrhythmic drugs with beta
      blocking activity.

PMID- 9244741
TI  - [Coronary stenting for treatment of intimal dissection and occlusive thrombosis
      during primary PTCA in acute myocardial infarction].
AB  - Coronary angioplasty during acute coronary syndrome, and particularly in MI,
      continues to involve a greater risk of acute and subacute occlusion. Stenting for
      acute or threatened vessel closure has a high initial success rate and reduces
      the need for emergency bypass surgery. Nevertheless, under these conditions
      intracoronary thrombus actually appears to be a relative contraindication to
      stent implantation. We report the successful implantation of two Palmaz Schatz
      stents to treat a coronary occlusion refractory to multiple ballooning during
      primary PTCA in myocardial infarction with angiographic evidence of intimal
      dissection containing thrombus. The good clinical improvement and the results of
      short- and long-term clinical angiographic follow-up confirm both the feasibility
      and effectiveness of using this technical approach to manage complications in
      acute and unstable syndromes.

PMID- 9244742
TI  - [Latent long QT syndrome: discription of a clinical case].
AB  - Latent forms of long QT syndrome have been already reported. We describe one case
      of a 27 years old female patient who experienced an episode of cardiac arrest
      after several puffs of salbutamole. The malignant arrhythmia causing the cardiac
      arrest was torsade de pointes degenerated into ventricular fibrillation. The
      patient ECG showed a normal QTc basal interval and the correct diagnosis was made
      by contemporary recording of the ECG and MAP during orciprenalina infusion. After
      drug infusion, we have recorded a MAP lengthening and a dispersion of MAP
      duration between the right ventricular apex and the right ventricular outflow
      tract. These modifications were concomitant with the appearance of "humps"
      (probably related to the presence of early afterdepolarizations), a QT interval
      lengthening and morphologic changes of the T and U waves.

PMID- 9244743
TI  - [Primary antiphospholipid antibody syndrome with left atrial intracardiac
      thombosis].
AB  - The present report describes a case of right atrial thrombus in an active 49-year
      old man with a primary antiphospholipid syndrome. In 1984, the patient was
      admitted for autoimmune hemolytic anemia; during the hospitalization it was
      diagnosed a chronic hepatitis B. In July 1991, the patient had fever, mild
      jaundice, splenomegaly and pancytopenia; a diagnosis of hairy cell leukemia was
      made but it was not subsequently confirmed. Interferon therapy was started and
      the patient's clinical course mildly improved. However, over the same year, he
      experienced again a clinical deterioration. Lumbar ischemic ulcers occurred. The
      patient underwent elective splenectomy. Bone marrow biopsy revealed
      mielodisplastic syndrome. Necrotizing vasculitis with granulomatosis was
      diagnosed. The patient's condition improved after splenectomy. Repeated
      laboratory tests showed positivity for antiphospholipid antibodies. Transthoracic
      and transesophageal echocardiography demonstrated the presence of a right atrial
      thrombus, confirmed by nuclear magnetic resonance. The patient was started on
      long-term anticoagulant therapy, that resulted effective in reducing thrombus
      size.

PMID- 9244744
TI  - [Measurements of productivity and efficiency of a first level director in a
      cardiology referral clinic. Their use in the final determination of work load in
      accordance with DL 29/1993].
AB  - BACKGROUND AND OBJECTIVES: The law demands that the work-load (WL) in the Public
      Health Service be defined, and also dictates audit criteria referring to: a) the
      total activities performed during the previous three years; b) the standard times
      (STD) required to perform the different activities; c) the degree of demand
      fulfillment (DDF). Aim of this study is to establish the WL of 19 cardiologists
      (C) operating in a referral Hospital. METHODS: We examined the years 1993-1995.
      We calculated all medical procedures (P) carried out by our Institute
      ("procedure" method), and we determined the theoretical time needed to perform
      them based on STD. The activities of the Coronary Unit (CCU) and of the Ward (W)
      have been evaluated based on the duty-time table ("presence" method). The sum of
      the hours calculated with the two methods is the theoretical duty-time per week
      (TDT = sigma P x STD Time + CCU hours + W hours). We then measured the actual
      duty-time (ADT). By comparing TDT and ADT we obtained an efficiency index EI =
      [(TDT - ADT)/TDT]%. The DDF has been estimated based on the waiting-lists.
      RESULTS: We noticed an increase in invasive P and related activities, and a
      stable trend or a small decrease in non-invasive P, except for echography. TDT
      was always found to be superior to ADT (1993: 731.3 vs 670; 1994: 742.7 vs 670.9;
      1995: 734 vs 652.1) with an increasing IE (8.3; 9.6; 11.1 respectively). We found
      rather high figures for extra hours per week (mean 31.6), C time (mean 34.9) and
      hours lost for vacation, illness, etc. (mean 137.5/week, equal to duty-time of
      more than three C). When GCS was considered, the total WL was 770 hours per week,
      equal to a duty-time of 19.25 C. CONCLUSIONS: WL evaluation allows a better
      understanding of operating conditions ina ward, it is essential when C are
      committed to pursue specific objectives, and it represents a basis to monitor
      efficiency. The reliability of WL largely depends upon STD; this underscores the
      fundamental role of Scientific Societies to prevent a tool intended for a better
      utilisation of human resources from becoming a pure instrument of cost
      containment.

PMID- 9244745
TI  - [Measurements of productivity and efficiency of a first level director in a
      cardiology referral clinic. Their use in the final determination of work load in
      accordance with DL 29/1993].

PMID- 9244746
TI  - [Do we die from myocardial apoptosis? Fashion and reality of different types of
      cell death in cardiovascular diseases].

PMID- 9244747
TI  - [What a doctor has to know].

PMID- 9244748
TI  - [Transmyocardial laser revascularization in patients with peripheral coronary
      atherosclerosis. Indications and preliminary results].
AB  - BACKGROUND: Surgical intervention for coronary artery disease (CAD) is determined
      by the viability of coronary artery branches. When peripheral coronary artery
      disease is present, conventional bypass grafting is not suitable. Research has
      recently been done on alternative methods such as transmyocardial laser
      revascularization (TMLR). TMLR works through the vascular connections that are
      present between the cardiac chambers and the myocardial muscle in the human
      heart. The creation of 1-mm transmural cardiotomies through a CO2 laser should
      improve myocardial perfusion. METHODS: From February to June of 1996, twelve
      patients (9 males and 3 females with a mean age of 67.8 +/- 4.6) with CAD (mean
      n0 of diseased vessels 2.7), angina (mean CCS class 3.5 +/- 0.5), mean ejection
      fraction 47.8% and viable ischemic myocardium on scintiscan in segments without
      graftable coronary branches, underwent TMLR at our institute. Nine of the 12
      patients also underwent associated CABG (mean number of anastomoses per patient:
      2.5). Cardiopulmonary bypass was never used, since coronary anastomoses and laser
      cardiotomies were performed on the beating heart. RESULTS: Perioperative
      mortality was 2/12 (16.6%). Postoperative inotropic support and diuretic therapy
      was required in most cases. At a mean follow-up period of 4.2 months, all
      remaining patients are still alive: 5/10 are angina-free (CCS 0), 4/10 are in CCS
      class 1 and 1/10 is in CCS class 2 (mean 0.6 +/- 0.7). CONCLUSIONS: We believe
      that TMLR could be considered an effective mean to treat symptomatic myocardial
      ischemic disease in which coronary bypass grafting is not suitable. During the
      immediate postoperative period, contractile myocardial dysfunction occurs in a
      high percentage of patients treated using TMLR and consequently it would be
      worthwhile to invest in further research.

PMID- 9244749
TI  - [White coat arterial hypertension and isolated systolic arterial hypertension:
      ultrasonography of the carotid arteries].
AB  - BACKGROUND: The prognosis of white coat hypertension is uncertain. The aim of
      this study was to evaluate the prevalence of atherosclerotic carotid lesions in
      subjects with white coat hypertension and clinical isolated systolic hypertension
      using 2D echo-color-doppler procedure. MATERIALS AND METHODS: Patients were
      initially selected through the sphygmomanometric measurement of blood pressure
      and subsequently through 24-hour blood pressure monitoring. Fifty-four subjects
      with white coat hypertension were studied in comparison with either 60
      normotensive subjects or 116 sustained isolated systolic arterial hypertensives.
      All patients underwent high-resolution B-mode echotomography of both carotid
      arteries, which made it possible to assess myointimal thickening and plaques. A
      thickness of > or = 0.95 mm, calculated as the mean of 5 measurements of the
      common carotid artery, 2.3 cm from the flow divider, was considered a sign of
      myointimal thickening, while plaques were represented by a focal thickening of >
      or = 2 mm, based on echogenic characteristics (hard, fibrous, mixed, soft and
      hemorrhagic) and site (common carotid, bifurcation, internal and external
      carotid). RESULTS: Normal carotid arteries, carotid arteries with myointimal
      thickening, or carotid arteries with at least one plaque, were similar in
      subjects with white coat hypertension and in normotensives. Instead, as compared
      with subjects with white coat hypertension, sustained hypertensives showed a
      pattern of intimal-medial thickening (p = 0.04) with-one or more plaques (p =
      0.005) on a much more frequent basis, while normal carotid arteries were less
      frequent (p = 0.0001). Plaques were most often localized at the common carotid
      artery and bifurcation and, less frequently, at the internal and external carotid
      arteries. Most often, the lesions were hard, less fibrous, mixed and soft.
      CONCLUSIONS: White coat hypertensives with clinical isolated systolic
      hypertension may represent a low-risk group. Long-term prospective studies are
      required in order to obtain a definitive prognosis of white coat hypertension.

PMID- 9244750
TI  - [Prognostic stratification after acute uncomplicated myocardial infarction:
      exercise test, echo-dobutamine test or both?].
AB  - OBJECTIVES: The aims of this study were: 1) to assess the relative prognostic
      value of predischarge dobutamine echocardiography (DE) and exercise
      electrocardiography (EE) in patients after a first uncomplicated acute myocardial
      infarction (AMI), and 2) to evaluate the optimal prognostic strategy by using the
      two tests in different combinations. METHODS: DE (dobutamine infusion 5 to 40
      micrograms/kg/min plus atropine 0.25 to 1 mg, if needed) and symptom-limited
      bicycle EE were performed in 208 patients (mean age 58 +/- 9 years, 90% males),
      on different days and in random order, 12 +/- 4 days after a first uncomplicated
      AMI and after pharmacological washout. A stress-induced dyssynergy and ST segment
      depression > 1 mm were considered criteria of positivity for DE and EE,
      respectively. Only spontaneous cardiac events were considered: cardiac death,
      reinfarction (= hard events), and unstable angina requiring hospitalization (=
      soft events). RESULTS: Thirty-eight events occurred during follow-up (16 +/- 13
      months; range: 1-44 months); 5 cardiac deaths, 6 reinfarctions and 27 unstable
      angina. Patients with a positive DE had a twofold increase in all event rates (26
      vs 12%, p < 0.01) and a fourfold increase in the rate of hard events (9 vs 2%, p
      < 0.05). In contrast, no statistically significant difference was observed in the
      distribution of the same events between patients with positive and negative EE.
      Both tests showed similar negative (DE 88%, EE 85%) and positive (DE 26%, EE 24%)
      predictive values. Among six different strategies (performing either DE or EE
      only in all patients; EE in all patients; EE in all patients and DE only in those
      with a positive EE; and DE only in those with a negative EE; EE in all patients
      and DE only in those with anterior AMI), EE only in patients with inferior or non
      Q AMI and DE only in those with anterior AMI), performing DE only in patients
      with a positive EE gave the highest predictive accuracy-74% (95% confidence
      intervals 68 to 80) for all events and 77% (95% confidence intervals 71 to 83)
      for hard events. CONCLUSIONS: In patients with a first uncomplicated AMI, DE is
      useful in identifying patients at high and low risk of future spontaneous cardiac
      events. The optimal strategy for prognostication of these patients is to perform
      EE in all and DE only in the ones with a positive EE.

PMID- 9244751
TI  - [The role of 2D-doppler electrocardiography in the early diagnosis of massive
      acute pulmonary embolism and therapeutic monitoring].
AB  - Early diagnosis is important for the prognosis of patients affected with
      pulmonary embolisms. The mortality rate ranges from 30% in untreated cases to 10%
      in cases getting early treatment. In this context, it is essential to obtain a
      correct diagnosis in order to start the best treatment for each patient. The aim
      of our study is to evaluated the contribution of mono- bidimensional
      echocardiography and color-doppler for the early diagnosis of acute massive
      pulmonary embolism. We examined 23 patients (14 women with a mean age of 67 +/-
      13 years; 9 men with a mean age of 58 +/- 16 years) who were referred to us for
      observation over a 30-month period. These patients had been admitted to the
      intensive care unit for suspected acute massive pulmonary embolism and the
      diagnosis was subsequently confirmed by a pulmonary scintigraphy. None of the 23
      patients showed a positive case history of previous heart disease and/or
      pulmonary disease. The patients were checked using 2D-doppler echocardiography,
      120 +/- 45 minutes from the onset of the symptoms. They were then divided into
      two groups (A and B) based on the presence or absence of thromboembolus in the
      right cavity of the heart. Seven patients (30%) revealed thromboemboli and were
      treated effectively with rt-PA (100 mg/2 hours). An increase in the size of the
      right ventricle with an affected rate RV/LV > 0.6 and the abnormal kinetics of
      the ventricular septum proved to be the most sensitive parameters for right
      ventricular overload, as signs of acute massive pulmonary ambolisms were observed
      in all 23 patients. Tricuspid regurgitation speed (from 2.9 to 3.6 m/sec) and
      peak systolic pulmonary pressure (67 mmHg) were recorded in all patients. Our
      observations suggest that the hemodynamic effects of an acute massive pulmonary
      embolism can be enumerated and monitored by analyzing ventricle size and septum
      kinetics. To summarize, echocardiography proved to be a simple and realistic
      test. It enabled correct diagnosis and made it possible not only to start
      thrombolytic therapy without requiring other exams, but also to monitor and
      evaluate the effects of this therapy.

PMID- 9244752
TI  - [Anti-Chlamydia pneumoniae antibodies and production of interleukin 6 in acute
      myocardial infarct].
AB  - Chlamydia pneumoniae (C.p.) has been correlated with acute myocardial infarction
      (AMI). High levels of anti-C.p. antibodies and circulating immune complexes
      containing C.p. lypopolyaaccharide (LPS) antigens have been demonstrated in AMI.
      LPS antigen and especially Chlamydial LPS is one of the best antigen and it is
      also a very good Interleukin inductor. Moreover, interleukin 6 (IL-6) has been
      observed in AMI patients. The aim of our study was to assess the possible
      relationships between anti-C.p. immune response and IL-6 production in AMI
      patients. We studied 17 consecutive patients with myocardial infarction (12 males
      and 5 females; mean age 62; range 46-72). Blood samples were obtained immediately
      after hospital admission. There were 17 control subjects (HCM) (mean age 62;
      range 45-72) who were matched for the main coronary risk factors (gender, age,
      diabetes, hypertension, hypercolesterolemia, smoking, family history of ischemic
      heart disease). In addition, we evaluated the AMI patients in a one-year follow
      up study (FU). RESULTS: High levels of C.p. IgG MIF were found in 82.3% of our
      AMI patients and in 29.4% of HCM subjects (p = 0.0000065). IgA-MIF were 70.5% in
      AMI patients and 29.4% in HCM (p = 0.0042). High levels of C.p. IgG and IgA anti
      LPS were found, with a very high prevalence rate of 76.4% and 64.7% in AMI
      patients, and both rates were 47.0% (p = 0.158; p = 0.489) in HCM. Very high
      levels of IL-6 were found (m = 54.38 pg/ml) in 100% of the AMI patients (normal
      values in our population: 0-10.86 pg/ml) and only detectable levels in 5.8% of
      HCM. A good linear correlation was demonstrated between IL-6 and IgA levels in
      the first sample (r = 0.655). The high levels of anti-C.p. IgG, IgA and IL-6,
      with a good correlation between IL-6 and IgA levels, may confirm the presence of
      an active infection and probably of a reinfection.

PMID- 9244753
TI  - [Benign mediastinal teratoma with pericardial symptoms. The utility of
      echocardiography in diagnosis].
AB  - The authors describe the clinical case of a 21-year-old girl who was admitted to
      the hospital because of pericardial symptomatology. On admission, a transthoracic
      echocardiogram revealed moderate pericardial effusion and an anterior
      parenchimallike mediastinal mass, that extended as far as the main vessels and
      the anterior wall of the right ventricle. This report was subsequently confirmed
      by a computed tomography chest scan. Due to the rupture into the pericardial
      cavity, which was followed by considerable pericardial effusion, she was
      immediately taken to the operating room for pericardiocentesis and the decision
      was then made in order to excise the mass. The hystological diagnosis revealed
      "benign cystic mature teratoma of the mediastinum". The authors' literature data
      is included, and the article also emphasizes the importance of using
      echocardiograms in casualties in order to obtain a differential diagnosis of
      chest pain.

PMID- 9244754
TI  - [Impact factor: analysis of four years of scientific activity in a national
      cardiology department].

PMID- 9244755
TI  - [What are the costs of pediatric cardiosurgery?].
AB  - A cost analysis of patients discharged from the Department of Pediatric
      Cardiology and Heart Surgery of "Bambino Gesu" Children's Hospital was performed.
      Analysis focused on the costs and revenue from Diagnosis-Related Group 108
      ("other cardiovascular procedures") during a six-month period in 1994 (n. = 76).
      The sample of 30 charts reviewed (MLOS 20.36 +/- 27.87 days) showed a mean cost
      of 30,381,000 italian lire (ITL) vs a revenue of ITL 23,545,800. The Pearson
      correlation coefficient between LOS and total cost was high (R = 0.85; p <
      0.001). Other cases in DRG 108 (n. = 46) had an MLOS of 29.13 +/- 25.25 days and
      a higher cost. We emphasize the usefulness of identifying the costs for patients
      grouped in a specific DRG in order to establish an accurate departmental budget
      as well as to ensure the financial survival of referral hospitals.

PMID- 9244756
TI  - [Coronary angioplasty: use and cost].
AB  - OBJECTIVES: The goal of the study was to examine the utilization of cardiac
      catheterization laboratory resources in surgical procedures in order to determine
      the cost impact of introducing new devices such as stents and atherectomy.
      METHODS: Detailed resource utilization and costs of each cardiac catheterization
      laboratory procedure performed in 1995 were determined. Costs were analyzed for
      single-vessel and multivessel coronary angioplasty, also taking into account the
      additional costs for coronary stent placement or for the use of directional
      atherectomy. RESULTS: The mean cost of a surgical procedure was ITL 8,280,010,
      while the mean cost for conventional coronary angioplasty was ITL 4,352,427 (ITL
      4,293,108 for single-vessel PTCA; ITL 5,072,841 for multivessel PTCA). The mean
      cost for a procedure with stent implantation was ITL 10,084,563. As compared to
      conventional angioplasty, coronary stenting had a 131.6% higher catheterization
      laboratory cost and an additional cath-lab resource utilization in terms of
      contrast medium (257 +/- 136 ml vs 216 +/- 109 ml, p = 0.018) and balloon
      catheter (1.97 +/- 1.27 vs 1.54 +/- 0.78, p = 0.0009). The cost for a directional
      atherectomy followed by stent placement was ITL 18827545, which is 332.5% higher
      than the cost of a conventional angioplasty. CONCLUSIONS: Coronary stents and
      directional atherectomy have a significant economic impact on catheterization
      laboratory resource utilization and costs. This aspect should be taken into
      consideration in analyzing the short- and long-term results of these techniques.

PMID- 9244757
TI  - [Cholesterol and statins].

PMID- 9244758
TI  - Application of the variable region in 16S rDNA to create an index for rapid
      species identification in the genus Streptomyces.
AB  - Partial nucleotide sequences (120 bp) of the 16S rRNA gene (rDNA) containing a
      variable alpha region were compared in 89 strains of the genus Streptomyces
      belonging to eight major clusters of category I in Bergey's Manual of Systematic
      Bacteriology. Fifty-seven kinds of partial 16S rDNA sequences were observed among
      the 89 strains. Forty-three of the strains were grouped into 11 'identity
      groups', based on the fact that the strains in each group shared an identical
      sequence in the 120-bp region. The results of a phylogenetic analysis based on
      the 16S rDNA 120-bp sequences revealed that 60 of the 89 strains could be
      categorized into seven clusters, each consisting of four or more strains. Based
      on these observations it was concluded that short nucleotide sequences bearing
      the variable alpha region are useful for Streptomyces species identification.

PMID- 9244759
TI  - [Molecular paleogenetics of primates].
AB  - Genetic distances between the major members of the primate order obtained from
      data on blood serum antigens, amino-acid sequences of intracell proteins,
      electrophoretic gene markers, and nucleotide sequences of nuclear and
      mitochondrial DNA are analyzed. Conclusions regarding phylogeny and systematics
      of the primate order based on evidence of molecular evolutionary genetics are
      discussed.

PMID- 9244760
TI  - [Extrachromosomal DNA spectrum of Bacillus thuringiensis Berliner and Bacillus
      sphaericus Meyer et Neide].
AB  - Analysis of the pattern of extrachromosomal DNA in different cultures of Bacillus
      thuringiensis and Bacillus sphaericus demonstrated a higher content of
      extrachromosomal DNA in B. thuringiensis than in B. sphaericus. The quantity and
      approximate molecular weights of the plasmids were determined. The assumption
      that the plasmid DNA content in B. thuringiensis strains is higher than in the
      other representatives of the genus Bacillus was confirmed.

PMID- 9244761
TI  - [Phenotypic characterization of Bacillus subtilis mutants with decreased
      exonuclease I activity].
AB  - A Bacillus subtilis strain containing a mutation decreasing exonuclease I
      activity by up to 25% as compared to normal cells of the original BD46 strain was
      developed. A decrease in B. subtilis exonuclease I activity increased the
      sensitivity of mutant cells to UV irradiation and mitomycin C, decreased the
      frequency of recombination during chromosomal transduction and transformation,
      decreased the frequency of transposon Tn917 translocation from plasmid to the
      bacterial chromosome, and did not affect the frequency of plasmid transformation.
      The corresponding mutation was mapped.

PMID- 9244762
TI  - [Isolation and properties of mutants devoid of pseudo-HPr activity of the
      fructose transfer system in Escherichia coli K12].
AB  - Mutants without pseudo-HPr activity intrinsic to the H domain of the FruB protein
      were obtained in Escherichia coli K12 through insertional mutagenesis by means of
      the MudIlac phage and TnPhoA transposon. For isolating these mutants, double
      mutants of enteric bacterium (ptsH fruR of ptsH fruS) were used as original
      strains. These double mutants were inactive with respect to the total HPr protein
      of the phosphoenolpyruvate-carbohydrate phosphotransferase system and could not
      provide constitutive synthesis of fructose-specific proteins of this system. The
      mutants obtained were designated fruH, mapped, and genetically characterized.
      Insertions were shown to be located in exactly the portion of the fruB gene that
      specifies synthesis of the H domain of the FruB protein. The fruH mutations
      decreased motility of bacterial both in a medium free of carbohydrates and in a
      medium with glucose, fructose, or maltose. In addition, fruH mutants with the
      MudIlac genome insertion had sharply decreased activity of beta-galactosidase.

PMID- 9244763
TI  - [Interaction of mutations of the genes for mutagen sensitivity mei-9, mei-41 and
      rad201 as affected by ionizing radiation].
AB  - Double mutants mei-41D5; rad(2)201G1 and mei-9a; rad(2)201G1 were constructed to
      study the interaction of these mutations in Drosophila exposed to gamma-rays. mei
      9 and mei-41 mutants are sensitive to the lethal effects of a broad spectrum of
      chemical and physical factors, while rad201 mutants are sensitive only to
      ionizing radiation. The results obtained showed that the interaction of mei-9 and
      rad201 mutations is additive and the interaction of mei-41 and rad201 mutations
      is epistatic. The maternal effect was demonstrated to be characteristic of all
      mutants tested even when larvae were exposed to radiation at a late stage of
      development.

PMID- 9244764
TI  - [Effect of the transposon at the singed locus on recombination in Drosophila
      melanogaster].
AB  - Recombination frequency in different combinations of unstable alleles of the
      sn49::Tn-clw system was studied. In some diallele combinations, an increased
      recombination frequency in the region of signed gene was found. The distribution
      of mutant progeny in the compounds was different in recombination and non
      recombinant classes. Restriction mapping of the Tn-clw transposon revealed that
      it contained conservative and variable sequences. Interallelic transitions were
      associated with rearrangement of the variable sequence and the signed sequences
      adjacent to the transposon.

PMID- 9244765
TI  - [Genetic analysis of differences in dopa decarboxylase activity between two
      Drosophila virilis lines differing in dopamine content].
AB  - Activity of dopa decarboxylase (DDC) in two Drosophila virilis lines differing in
      dopamine (DA) content was investigated. The activity was shown to be
      significantly higher in flies with lower DA content. A possible reason for this
      phenomenon is discussed. Genetic analysis of the difference showed that DDC
      activity in Drosophila virilis is controlled by single autosomal gene (or a
      cluster of tightly linked genes).

PMID- 9244766
TI  - [Gene diffusion in hybrid populations of green frogs Rana esculenta L., 1758
      complex (Amphibia, Ranidae) from the Dnepr Basin].
AB  - Population-genetic analysis of hybrid populations of green frogs from the Dnepr
      basin demonstrated limited gene introgression in diploid hybrids in addition to
      semiclonal reproduction, which is typical for Rana esculenta hybrids.
      Introgression is largely confined to the Ldh-B locus: the gene of R. lessonae is
      introduced into the R. ridibunda genome. This phenomenon is unstable as it is
      geographically restricted and absent in populations of the E-L type.

PMID- 9244767
TI  - [Variability of pheomelanin content in wool of Karakul lambs and the problem of
      phenetics of color].
AB  - In samples of wool from 1,229 differently colored newborn Astrakhan lambs, the
      total content of melanins and the proportion of pheomelanin in the total melanin
      were studied by the method of electron magnetic resonance spectometry. An
      analysis of the corresponding computer data base revealed that the distribution
      of the samples with respect to the proportion of pheomelanin had at least four
      characteristic maximums; 1-6, 9-10, 28-29, and 39% of pheomelanin. The former two
      maximums were characteristic for the brown and Karakalpak sur colors, and the
      latter two maximums, for red-brown kambar color. White hair tips, characteristic
      for the sur color, and the proportion of pheomelanin were combined almost
      independently; therefore the possibility is discussed of classifying these
      characters as independent phenes, and some variants of sur, as their
      combinations.

PMID- 9244768
TI  - [Effect of domestication of the silver fox on the main enzymes of serotonin
      metabolism and serotonin receptors].
AB  - In silver foxes significant alterations in the activities of basic enzymes of
      neurotransmitter serotonin metabolism as well as in the densities of receptors
      caused by selection for the absence of the aggressive defensive reaction to man
      were demonstrated. In the midbrain and hypothalamus of animals selected for the
      absence of aggressive behavior, the activity of tryptophan hydroxylase, the key
      enzyme of serotonin biosynthesis, was found to be remarkably higher than in
      animals selected for highly aggressive behavior. Domesticated animals were
      characterized by low activity of the main enzyme of serotonin catabolism,
      monoamine oxidase type A, increased Michaelis constant km, and an unchanged
      maximum reaction rate (Vmax). No changes in the specific binding of [3H]
      ketanserin and [3H]-8-OH-DPAT in the frontal cortex of domesticated foxes were
      revealed; however, in the hypothalamus, the low values of Bmax for the [3H]-8-OH
      DPAT specific binding were observed, indicating the decreased density of the 5
      HT1A receptors. It is assumed that the transformation of a wild aggressive animal
      into a domesticated one taking place during directional selection is caused by
      hereditary alterations favored by artificial selection in the activity of the
      main enzymes of serotonin metabolism and serotonin receptors.

PMID- 9244769
TI  - [Population-demographic structure of the population of Kurskaia district.
      Migration processes].
AB  - Analysis of marital structure revealed that 82% of men and 77% of women that
      contracted marriages in the Kurskaya oblast (administrative region) in 1987-1990
      were born in this region. The average coefficient of demographic migration in the
      Kurskaya oblast was m = 0.345. The majority of migrants to the Kurskaya oblast
      were from neighboring areas: Central and Central Chernozem Zones of Russia,
      Ukraine, and Moldova. Marriage assortativeness with respect to the birthplaces of
      the spouses was K = 0.090. Migration activity increased with urbanization of the
      population. Migration structure of local populations was determined by mode,
      level, and direction of interaction between the processes underlying it.

PMID- 9244770
TI  - [Population-demographic structure in the Kurskaya district. Isolation by
      distance].
AB  - The population of the Kurskaya oblast (administrative region) was described using
      the Malecot's model of isolation by distance. Differences in inbreeding level
      between populations of raions (districts) were found; the differences were
      determined by degrees of urbanization, age, and effective size of the
      populations. In the center of the oblast, an area was found with the minimum mean
      square distance between birthplaces of spouses, low effective migration pressure,
      and high isolation by distance. In populations of raions, a relationship was
      found between population inbreeding level and incidences of congenital
      malformations (CM) and multiple congenital malformations (MCM), which affected
      the viability of infants.

PMID- 9244771
TI  - [Analysis of nucleotide combinations in types of the control region of human
      mitochondrial DNA].
AB  - Nucleotide combinations of polymorphic sites of the mitochondrial DNA (mtDNA)
      control region were analyzed in human populations of different ethnic region. It
      was demonstrated that the combination of C and T at positions 16,126 and 16,294,
      respectively, of the mtDNA control region was specific for Caucasoids. In eastern
      Slavic mtDNA types, this combination of nucleotides was associated with
      nucleotide substitutions G-A at position 14,905 of the cytochrome b gene and T-C
      at position 16,519 of the control region. Results of phylogenetic analysis of the
      types of mtDNA control region were used to estimate the evolutionary position of
      Eastern Slavs Caucasoid populations.

PMID- 9244772
TI  - [Similarity of geographic distribution of frequencies of p(c) allele of
      erythrocyte acid phosphatase and BamHI-3/MspI-4 types of mitochondrial DNA in
      Caucasoid human populations].
AB  - The frequencies of the pC allele of red cell acid phosphatase (AcPI) and a group
      of mitochondrial DNA (mtDNA) types BamHI-3/MspI-4 were shown to have similar
      geographic distribution in Caucasoid populations of six regions of Europe and
      Asia. The maximum frequency values of these markers were revealed in southern and
      southeastern Europe. The possibility of associations between these variants of
      polymorphism in the genotype-mitotype system is discussed. The geographical
      gradients of pC and BamHI-3/MspI-4 correlate with the directions of neolithic
      migrations of Caucasoids from the Near East to Europe. The region of maximum
      frequency values of pC and BamHI-3/MspI-4 is supposed to be largely consistent
      with the area where considerable enhancing of the population size of neolithic
      migrants from the Near East and their mixing with the ancient population of
      Europe occurred.

PMID- 9244773
TI  - [Dependence of the concentration of maternal serum markers on the haptoglobin
      gene].
AB  - This paper is the first in a series devoted to the investigation of the possible
      effect of maternal genotype on the levels of fetal alpha-fetoprotein (AFP) and
      human chorionic gonadotrophin (HCG) entering maternal blood. We studied the
      possible association between the maternal haptoglobin system and levels of
      maternal AFP and HCG, which are markers of fetal pathology. Haptoglobin types
      were determined in groups of pregnant women with different levels of serum
      markers. Distribution of haptoglobin types differed from the theoretically
      expected in one out of five groups tested. In the group with low AFP level, a
      significant decrease in frequency of the Hp*2 allele was found. A statistically
      significant decrease of the mean haptoglobin concentration in the group with low
      levels of AFP and elevated levels of HCG was observed. A reduction in serum
      haptoglobin concentration was shown to be accompanied by a decrease of serum iron
      concentration. The possible mechanism underlying the influence of maternal
      genotype on the levels of AFP and HCG in maternal blood are discussed.

PMID- 9244774
TI  - [Determination of the genotoxicity of fullerene C60 and fullerol using the method
      of somatic mosaics on cells of Drosophila melanogaster wing and SOS-chromotest].
AB  - Genotoxicity of fullerene C60 was been determined in a prokaryotic in vitro test
      and in an eukaryotic in vivo system. The SOS chromotest of fullerene C60 in the
      Escherichia coli strain PQ37 revealed no genotoxicity either with or without
      activation of the rat liver homogenate. To perform the somatic mutation and
      recombination genotoxicity test (SMART) on somatic wing cells, Drosophila
      melanogaster larvae were grown on a standard medium with or without fullerene
      dope. No statistically significant differences were observed at the same
      fullerene concentrations in the SOS chromotest (0.45 micrograms/ml). Only at the
      highest possible fullerene concentration of 2.24 micrograms per 1 ml medium, a
      slight genotoxic effect was observed in wing cells. Fullerol demonstrates no
      mutagenic effect at a concentration of 2.46 mg/ml.

PMID- 9244775
TI  - [Selection of mice for brain weight].
AB  - The results of two experiments on selection of laboratory mice for large and
      small brain weight are presented. Selection was based on the regression
      relationship between body and brain weight. This allowed considerable differences
      in brain weight to be obtained accompanied by insignificant interlinear
      differences in body weight compared to the range of intralinear variation. The
      two lines of mice with a large and small brain weight (F9-F10) differed
      significantly in brain weight. The absolute difference was 60-70 mg, i.e.,
      approximately 13% of the brain weight in the original heterogeneous population.

PMID- 9244776
TI  - Type-4 pili: biogenesis, adhesins, protein export and DNA import. Proceedings of
      a workshop. Rottach-Egern, Germany, 26-29 November 1995.

PMID- 9244777
TI  - [Comparative informative value of chromosome aberrations and sister chromatid
      exchanges in the evaluation of metals in the environment].
AB  - Simultaneous recording of the frequency of chromosomal aberrations and sister
      chromatid exchanges supplements data on the nature of genetic disorders in the
      sanitary and toxicological assessment of metals polluting the environment. A
      obvious threshold of genetic effects of metals was not revealed in the context of
      chromosomal aberrations and sister chromatid exchanges. Methods for detecting the
      genotoxicity of metals await further search.

PMID- 9244778
TI  - [Comprehensive hygienic examination of drainage areas, water supply stations and
      drinking water].

PMID- 9244779
TI  - [Clinical and hygienic aspects of the systematization of industry-dependent
      prenosologic changes in the body].
AB  - The traditional aspect of prenosological changes occurring in workers exposed to
      industrial agents was considered from the current clinical and hygienic
      standpoints. A working classification of occupationally dependent prenosological
      changes was proposed, which identifies categories of those with and without
      clinical manifestations. The classification covers all the most important and
      currently known consequences of adverse effects on workers contacting with
      hazardous agents. It reflects not only theoretical aspects, but the practical
      value of the classification.

PMID- 9244780
TI  - [Comparative hygienic characterization of main stages of steel casting industry].

PMID- 9244781
TI  - [Level of selenium supply for inhabitants of the Northern economic area of
      Russia].
AB  - Human selenium levels were estimated in 28 towns and settlements of the Murmansk,
      Vologda, Arkhangelsk regions and Karelia. These were found to be 90-102
      micrograms/l in these areas, the lowest ones being detected in Petrozavodsk.
      Kondopoga, Suoyarvi, and Kovdor, the highest in Kola. The findings suggest that
      the higher selenium levels in the population in the north and south of the
      regions (the Murmansk and Vologda regions) is provided by the imported wheat
      flour with high selenium levels. They show it necessary to transport foodstuffs
      containing selenium into the areas where there may be this compound deficiency.

PMID- 9244782
TI  - [Microbiological contamination of fish in the delta of Volga].
AB  - Examining 213 bacteriological samples from 57 pike perch has revealed the high
      contamination of the fish with Enterobacteria in the branchia and intestine,
      which spread into the viscera and tissues. In the kidney there prevalent
      Escherichia coli (27.3%). Enterobacteria (20.), and Edvardsiella (16.6). The
      liver most commonly displayed yeasts and fungi (18.2%). Citrobacteria (14.3).
      Acinobacteria (14.3%). Many microbial strains had proteolytic and hemolytic
      activities and a considerable resistance to sodium chloride (7.5%).
      Acinobacteria, Providencia, and Proteus remain viable in its 10% solution. The
      findings suggest that the foods from the pike perch should undergo thermal
      treatment and a thorough bacteriological monitoring from its raw material to
      finished products to be made.

PMID- 9244783
TI  - [Heavy metal content of the hair of children in industrial cities].
AB  - Heavy metals are most common pollutants in large industrial cities. Differences
      were first shown in the distribution of concentrations of toxic and biogenic
      heavy metals in the hair of children. Zinc and copper had dispersion close to
      normal values, whereas lead, cadmium, and nickel had asymmetric dispersion.
      Scales were first developed for rating the levels of heavy metals in the
      children's hair in cities. A typology of microareas was also first developed by
      the level of metal pollution. The permanent stay of children in the highly
      polluted areas causes a high accumulation of lead in the hair and it is a risk
      factor of morphofunctional abnormalities and chronic diseases.

PMID- 9244784
TI  - [Dynamics of puberty levels in girls of Moscow].
AB  - In the past 20 years, puberty has tended to change among the female population of
      Moscow. The menarche age has increased from 12.6 to 13.0 years. Increases in the
      variability of this parameter was revealed. The findings suggest that further
      rise in puberty age can be expected among Moscow girls in the nearest future.
      This generates the need to pay more attention to the physical development of
      adolescents, a future productive and reproductive potential of the country.

PMID- 9244785
TI  - [Substantiation of MAC of crotonaldehyde in environmental air].
AB  - The reflex and resorptive effects of crotonaldehyde was studied. The maximum
      acceptable concentration (MAC) of crotonaldehyde was established to be 0.025
      mg/m3, the mean daily MAC recommended to be 0.003 mg/m3, Hazard Class 2. It was
      shown that nasopharyngeal mucosal morphological changes in laboratory animals
      might serve as significant criteria for the action of the agent having an
      irritant effect.

PMID- 9244786
TI  - [Health status of mining technical school students under present ecological
      conditions of Donets Basin].
AB  - The examinations indicated that the students of mining colleges from Donbass
      showed unfavourable changes in their health status, including those in their
      immunobiological resistance and functional status. There was a direct
      relationship between the levels of environmental pollution and the body's
      changes, i.e. those in the cardiovascular, respiratory, muscular, and nervous
      systems. Recommendations for health promotion in the students are given in the
      paper.

PMID- 9244787
TI  - [Health status of school children in experimental teaching].

PMID- 9244788
TI  - [Health evaluation of radioactive pollution of the environment].

PMID- 9244789
TI  - [Relationships "structure--methemoglobin-forming activity" in the series of
      aromatic amines].

PMID- 9244790
TI  - [Health of Moscow's population].

PMID- 9244791
TI  - [Ecological-hygienic aspects of the organization of monitoring of the dwelling
      environment].

PMID- 9244792
TI  - [Study of allergenic factors in the environment (review)].

PMID- 9244793
TI  - [Regularities of transformation of organic compounds in the environment].

PMID- 9244794
TI  - [Improvement of sanitary legislation of the Russian Federation].

PMID- 9244795
TI  - [Hygienic measures in enterobiasis control].

PMID- 9244796
TI  - [Cytological status of mucous membranes as a criterion of ecological risk].

PMID- 9244797
TI  - [Determination of methyl sulfide compounds in biological fluids].

PMID- 9244798
TI  - [Definition of concepts and systematization of hazardous substances].

PMID- 9244799
TI  - [A method of assessing the environment-population health system].

PMID- 9244800
TI  - Dental age determination in young bushbabies.

PMID- 9244801
TI  - XXV European Muscle Conference. La Grande Motte, Montpellier, France, 14-17
      September 1996.

PMID- 9244802
TI  - Notice of duplicate publication.

PMID- 9244803
TI  - JADA readers favor a practical approach.

PMID- 9244804
TI  - Creep rupture of wallaby tail tendons.
AB  - The tail tendons from wallabies (Macropus rufogriseus) suffer creep rupture at
      stresses of 10 MPa or above, whereas their yield stress in a dynamic test is
      about 144 MPa. At stresses between 20 and 80 MPa, the time-to-rupture decreases
      exponentially with stress, but at 10 MPa, the lifetime is well above this
      exponential. For comparison, the stress on a wallaby tail tendon, when its muscle
      contracts isometrically, is about 13.5 MPa. Creep lifetime depends sharply on
      temperature and on specimen length, in contrast to strength and stiffness as
      observed in dynamic tests. The creep curve (strain versus time) can be considered
      as a combination of primary creep (decelerating strain) and tertiary creep
      (accelerating strain). Primary creep is non-damaging, but tertiary creep is
      accompanied by accumulating damage, with loss of stiffness and strength. 'Damage'
      is quantitatively defined as the fractional loss of stiffness. A creep theory is
      developed in which the whole of tertiary creep and, in particular, the creep
      lifetime are predicted from measurements made at the onset of creep, when the
      tendon is undamaged. This theory is based on a 'damage hypothesis', which can be
      stated as: damaged material no longer contributes to stiffness and strength,
      whereas intact material makes its full contribution to both.

PMID- 9244805
TI  - Fatigue rupture of wallaby tail tendons.
AB  - Wallaby tail tendons fail after repeated application of stresses much lower than
      would be needed to break them in a single pull. We show that this a fatigue
      phenomenon, distinct from the creep rupture that occurs after prolonged
      application of a constant stress. The two phenomena are disctinguished by
      experiments in which tensile stress is cycled at different frequencies, ranging
      from 1 to 50 Hz.

PMID- 9244806
TI  - Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis
      factor alpha-inducible expression of the granulocyte colony-stimulating factor
      (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human
      fibroblasts.

PMID- 9244807
TI  - Proceedings of the biennial meeting of the World Institute of Ecology and Cancer
      and the European Institute of Ecology and Cancer. Bursa, Turkey, October 6-8,
      1995.

PMID- 9244808
TI  - [Effects of repetitive physical training on neurogenic regulation of heart rate
      in healthy subjects].

PMID- 9244809
TI  - [Effects of 17 beta-estradiol on nitric oxide and ventricular myocardium
      metabolism].

PMID- 9244810
TI  - Carpal tunnel syndrome as a herald of autoimmune rheumatic disorders.

PMID- 9244811
TI  - Kiwi conundrum: Screening for prostate cancer.

PMID- 9244812
TI  - Common ground found: "Overall cancer mortality rates are falling".

PMID- 9244814
TI  - A metal ring embedded in the hypopharynx.

PMID- 9244813
TI  - [Translation and validation of the questionnaire "Tinnitus Handicap
      Questionnaire, 1990].
AB  - OBJECTIVE: The Tinnitus Handicap Questionnaire (THQ) measures subjective tinnitus
      handicap in terms of emotional, social, and health impact (factor 1), hearing
      (factor 2), and perception of tinnitus (factor 3). A French version of the THQ
      was used with 178 tinnitus sufferers in ENT consultation. Internal validity was
      confirmed by correlations between (i) semigroups of items (Cronbach's alpha),
      (ii) item and total scores, and (iii) individual items, for each factor
      (Pearson's r), and was found to be strong (alpha = .90). All items (except 25 and
      26) showed strong total-score correlations (.30 < or = r < or = .74). All factor
      1 items intercorrelated strongly (.34 < or = r < or = .70). The factor 2 axis was
      coherent, with interitem correlations between .46 and .74, and its concurrent
      validation in strong factor 2 items correlations with hearing loss, if any
      (multiple linear regression: r = .67, p < .0001). Moreover, hearing-impaired
      (mean = 44.47 +/- 31.13) and normal-hearing (mean = 15.2 +/- 21.10) factor 2
      scores were significantly different. CONCLUSION: As with the original THQ, factor
      3 items were not strongly intercorrelated; moreover, items 25 and 26 failed to
      correlate with total score, suggesting that factor 3 is to be regarded with great
      caution.

PMID- 9244815
TI  - [Gamma-linolenic-acid-rich borage seed oil capsules in children with atopic
      dermatitis. A placebo-controlled double-blind study].
AB  - We investigated the effect of gamma-linolenic-acid from borage seed on atopic
      dermatitis of children. In a placebo-controlled, double-blind manner we studied
      24 patients, 3-17 years old. Every patient received 360 mg of gamma-linolenic
      acid daily, independent from sex and age; the same amount of corn seed-oil served
      as placebo. After 10 to 14 weeks of treatment there was no improvement of the
      eczema in the verum phase compared to placebo. Both groups showed improvement
      while taking placebo. This result could be seen in the objective investigations
      (Costa-Score, 3 times per treatment period) as well as in the daily patients
      documentation. The patients whose eczema has improved under borage seed-oil (n =
      10) had no special characteristics, so that we could not identify any responder
      type.

PMID- 9244817
TI  - [Subacute sclerosing panencephalitis (SSPE) as differential diagnosis in severe
      personality changes and ataxia--case report and literature review].
AB  - An 8 year old girl presented with progressive change of personality and spastic
      ataxia since 4 weeks. A year before she had developed focal grand-mal-seizures;
      at this time laboratory and radiologic findings were normal. The EEG on admission
      demonstrated marked changes with partially focal, partially generalized
      hypersynchronic activity, but no SSPE-typical Radermecker-complexes. There were
      no cells in the cerebrospinal fluid (CSF), a slightly increased level of protein
      and a normal glucose. Isoelectric focusing showed predominantly measles-specific
      oligoclonal IgG bands in the CSF. In the magnetic resonance tomography multiple
      focal white matter lesions in the basal ganglia as well as in cortical and
      occipitoparietal regions could be seen. At the age of two the girl had suffered
      from measles, the child didn't receive any vaccination. The combination of
      history, CSF-, MRI-results and EEG lead to the diagnosis of subacute sclerosing
      panencephalitis (SSPE). After 3 months the clinical and radiological
      abnormalities had markedly increased. On the background of this history SSPE
      should be considered as differential diagnosis in patients with changes of
      personality.

PMID- 9244816
TI  - [Long-term monitoring of therapy-induced computerized tomographic cranial changes
      in children with acute lymphoblastic leukemia].
AB  - PURPOSE: Long-term follow-up of cranial CT scans of children with acute
      lymphoblastic leukemia and evaluation of the influence of chemo- and radiotherapy
      on the CCT changes. PATIENTS AND METHODS: CCT scans of 68 children with non-B-ALL
      were analyzed retrospectively for signs of atrophy and changes in density.
      Patients were treated between 1981 and 1990 at the St. Anna Childrens Hospital
      Vienna according to the ALL-BFM protocols. Children were examined with CCT in
      defined periods from diagnosis until 3 years after cessation of treatment. As a
      control group served 69 patients with solid tumors who had not received
      corticoids or cranial irradiation. RESULTS: At the initial examination 56% of the
      ALL-patients showed CCT changes, 85% of these patients had already received
      corticoids. In the control group only 20% of the CCTs were found abnormal (p =
      0.005). In both groups an age-dependence was found: 64% of the ALL-patients under
      five years of age and 22% of the patients above 5 years had initial CCT changes
      (p = 0.001). In the control group 39% of the patients under five years of age and
      7% of the older patients showed CCT changes at the beginning of treatment (p =
      0.003). The highest incidence of abnormal CCT scans (68%) was seen during
      intensive chemo- and radiotherapy. Until the end of therapy the incidence of
      abnormal CCTs decreased to 32%. After cessation of antileukemic therapy 35% of
      the patients whose CNS-prophylaxis included cranial irradiation, and 12% of the
      non-irradiated patients had abnormal CCT scans. CONCLUSION: Corticoids can cause
      reversible signs of cerebral atrophy. In the assessment of CCTs a physiological
      age-dependence of the volume of the CSF compartment has to be taken into
      consideration. The main reason for non-reversible CCT changes is the CNS-
      prophylaxis, above all the cranial irradiation, whereby younger children seem to
      be particular vulnerable.

PMID- 9244818
TI  - [Cerebral vein and sinus thrombosis--an important cause of benign intracranial
      pressure increase in childhood].
AB  - The syndrome of raised intracranial pressure without any space-occupying lesion
      (pseudotumor cerebri) is still of unknown etiology. To some degree, secondary
      causes can be found. With respect to the therapeutical possibilities, a
      clinically important cause is the thrombosis of a major cerebral sinus. In
      children it is sometimes associated with otitis media. However, clinical signs of
      mastoiditis can be missed because of previous antibiotic treatment. We observed
      11 children with pseudotumor cerebri. Four children suffered from an occlusion of
      a lateral major sinus after otitis media. The treatment with heparin in the acute
      stage and later on with acetylsalicylic-acid led to complete recovery. Our
      results suggest that the thrombosis of a major cerebral sinus induced by an
      otitis media is a frequent cause of pseudotumor cerebri in children and should be
      excluded by MRI or angiography in any doubtful case. In contrast to the treatment
      of adults, long term anticoagulation is not necessary.

PMID- 9244819
TI  - [Pulmonary sling or ring-sling complex? respiratory problems--diagnosis, therapy,
      prognosis].
AB  - PS is a rare congenital vascular anomaly in which the left pulmonary artery
      originates from the right pulmonary artery and courses between trachea and
      esophagus to the hilus of the left lung causing compression of the right mainstem
      bronchus and trachea. In about half of all cases this vessel anomaly is
      associated with tracheo-bronchial and/or cardiovascular malformations. We present
      6 patients with PS concentrating on the accompanying malformations of the
      tracheobronchial tree. All patients had the typical symptoms of wheezing and
      stridor already in early infancy. 3 patients showed concomitant tracheobronchial
      anomalies. 2 patients had additional cardiovascular deformities. In 3 of the
      patients the positive clinical course allowed conservative therapy. In the case
      of 2 further patients the respiratory problems demanded surgery, one of this
      patients died. A further patient died after palliative surgery of cardiac
      anomaly.

PMID- 9244820
TI  - [A rare combination of partial trisomy 9 with pulmonary atresia].
AB  - We report of an previously unpublished combination of partial trisomy 9 and a
      membranous pulmonary atresia with a large conotruncal ventricular septal defect.
      The dystrophic female, term newborn presented after delivery with microcephaly,
      prominent nose and several other facial and skeletal deformities. The
      echocardiography and angiography showed a membranous pulmonary atresia with
      ventricular septal defect. Chromosomal analysis revealed a partial trisomy of the
      short arm with parts of the long arm of chromosome 9 and a small part of the long
      arm of chromosome 4. A surgical repair of the heart defect was not performed by
      the known high risk of severe mental retardation of partial trisomy 9. The child
      died at the age of six months.

PMID- 9244821
TI  - [Functional tricuspid atresia in a newborn infant with cardiac rhabdomyoma].
AB  - Cardiac rhabdomyomas are benign tumours closely associated with tuberous
      sclerosis. We report on a neonate with a cardiac rhabdomyoma, which simulated
      tricuspid atresia with duct-depending pulmonary perfusion due to almost complete
      obliteration of right ventricular cavum. Under infusion of prostaglandin E1 the
      newborn stabilized and was successfully operated on the 3rd day of life. We
      conclude that successful tumour resection is possible in neonates with cardiac
      rhabdomyomas causing relevant hemodynamic obstruction.

PMID- 9244822
TI  - [Olivo-ponto-cerebral hypoplasia--case report of a neurodegenerative disease
      manifesting at birth with a fatal outcome].
AB  - We report on a boy with pontocerebellar hypoplasia Type II according to the
      classification of Barth. The clinical signs were noted at birth and consisted of
      muscular hypertonus, central hypopnoe requiring artificial ventilation, chorea,
      hyperthermia above 40 degrees C and myoclonic seizures resistant to all
      therapeutic modalities. At birth, the boy was noted to have macrocephaly, but was
      microcephalic by 3 months of age. He failed to develop any mental or motor
      facilities. After cessation of all therapy the child died at the age of 3 1/2
      months. Postmortem examination of the brain revealed loss of neurons and gliosis
      affecting the olivo-ponto-cerebellar system, signs characteristic of PCH.

PMID- 9244823
TI  - [Vomiting as main symptom: unusual presentation of a hyperthyroidism in a 12-year
      old boy].
AB  - A twelve year old boy presented with a sudden onset of recurrent nausea and
      vomiting. During the past six weeks he had a weight loss of 13 kg. While he was
      in the hospital, persistent tachycardia and a slightly elevated blood pressure
      were noted. The gastroenterologic, cardiologic and neuropediatric examinations
      were normal. To exclude the differential diagnosis of hyperthyroidism, thyroid
      hormones were checked. They showed clearly elevated levels of tri-iodothyronine
      and thyroxine, while thyrotropin was suppressed. The boy did not have a goiter.
      Under thyrostatic therapy his clinical condition improved quickly. Among our 20
      patients with hyperthyroidism he was the only one whose main symptom was severe
      vomiting.

PMID- 9244824
TI  - The XVIII Symposium of the International Association for Comparative Research on
      Leukemia and Related Diseases (IACRLRD) on Leukemia and Lymphoma/Pathogenesis and
      Treatment/Molecular Aspects. Kyoto, Japan, 29 October - 3 November 1995.

PMID- 9244825
TI  - Application of database systems in diabetes care.
AB  - The St Vincent Declaration includes a commitment to continuous quality
      improvement in diabetes care. This necessitates the collection of appropriate
      information to ensure that diabetes services are efficient, effective and
      equitable. The quantity of information, and the need for rapid access, means that
      this must be computer-based. The choice of architecture and the design of a
      database for diabetes care must take into account available equipment and
      operational requirements. Hardware topology may be determined by the operating
      system and/or netware software. An effective database system will include: user
      friendliness, rapid but secure access to data, a facility for multiple selections
      for analysis and audit, the ability to be used as part of the patient
      consultation process, the ability to interface or integrate with other
      applications, and cost efficiency. An example of a clinical information database
      for diabetes care, Diamond, is described.

PMID- 9244826
TI  - Introduction of the Lester Brown Resident Award.

PMID- 9244827
TI  - [Inspiration-triggered vasoconstrictive episodes in healthy subjects, in patients
      with diabetes mellitus and in patients with clinically manifest polyneuropathy of
      variable origin. A simple Doppler ultrasound test to assess the autonomic
      vascular functional unit of the upper extremity].
AB  - BACKGROUND: A cost- and time efficient ultrasound-Doppler-test is introduced to
      evaluate the function of autonomic innervation of the upper limb. A voluntary
      inspiratory vasoconstrictor episode (VICE) after a provoked deep inspiration,
      transmitted via sympathetic nervous system, can be demonstrated at the radial
      artery using basic Doppler equipment. PATIENTS AND METHOD: VICEs were
      investigated in 30 healthy subjects (group A), in 20 patients with diabetes
      mellitus without clinical signs of polyneuropathy (group B) and in 20 patients
      with clinically manifest polyneuropathy (group C). RESULTS: In all healthy
      subjects a two minutes arterial occlusion led to a decrease of resistance index
      (RI) lower than 0.9 indicating sufficient hyperemia. RI during VICE increased to
      1.0 in all healthy subjects. In 50% of the patients of group B as well as in 50%
      of the patients of group C the test revealed abnormal findings suggesting a
      disorder of the functional peripheral neurovascular unity.

PMID- 9244828
TI  - [Physicians' attitude in the treatment of incompetent patients. Comparison
      between East and West Germany].
AB  - BACKGROUND: Health care decision-making in incompetent severely ill patients
      presents a number of difficult medical, ethical and legal problems for the
      physician. The factors and the degree to which various factors contribute to such
      decisions have rarely been investigated. SUBJECTS AND METHODS: 310 physicians
      from the state of Baden-Wurtternberg (Western Germany) and the state of
      Mecklenburg (eastern Germany) were asked by means of a questionnaire to rate the
      importance of eight factors in their health care decisions in the elderly.
      RESULTS: Both, ethical concerns and patients' wishes emerged as the most
      important factors for decisions in both subsamples. However, significant
      differences in the degree to which the factors hospital costs, patients' and
      family wishes, the level of dementia and the patients' age contribute to their
      decisions could be found between the answers of the doctors of the two lands.
      CONCLUSIONS: The socialization of the physicians in different health care and
      social systems seems to be one of the most important reasons for different health
      care decisions in old and incompetent patients.

PMID- 9244829
TI  - ["Inadvertent" use of alcohol-containing tonics in pregnancy].

PMID- 9244830
TI  - [Splenomegaly and interstitial lung disease].

PMID- 9244831
TI  - [Diagnosis of osteoporosis].

PMID- 9244832
TI  - [Interferon therapy and autoimmunity].
AB  - The treatment of viral hepatitis or malignomas with interferon (IFN) can increase
      the incidence of autoimmune disease. This paper reviews published case and study
      reports. The incidence of overt autoimmune diseases under IFN treatment is about
      3%. Autoantibodies can be detected in 23% of the patients. Autoimmune thyroid
      diseases are the most frequent ones, but nearly all autoimmune diseases can
      occur. Beside benign and reversible courses chronic developments and lethal
      outcomes are possible. Actual concepts concerning the pathogenesis of IFN
      associated autoimmunity include induction of MHC and other molecules as well as
      the modulation of lymphocyte functions. Clinical and paraclinical controls are
      necessary under treatment with IFN and during follow-up.

PMID- 9244834
TI  - [Fluorescence in-situ hybridization (FISH). Method and application].

PMID- 9244833
TI  - [Mineralocorticoid-induced hypertension].
AB  - Several important advances have been made in the pathogenesis of
      mineralocorticoid induced hypertension. A hybrid gene was found to be responsible
      for glucocorticoid remediable hypertension. This extra gene contains fragments of
      11-beta-hydroxylase and aldosterone synthase. The hybrid gene is the result of an
      unequal crossing-over of the two genes located in close proximity on chromosome
      8, and leads to the production of aldosterone and the hybrid steroids 18
      hydroxycortisol and 18-oxocortisol. These hybrid steroids are also detected in
      patients with aldosterone producing adenoma but not in patients with
      hyperaldosteronism due to bilateral adrenal hyperplasia. In Apparent
      "Mineralocorticoid Excess", inherited as an autosomal recessive disorder, an
      increased ratio of urinary cortisol metabolite to cortisone is diagnostic. The
      syndrome is due to a deficiency of the renal enzyme 11-beta-hydroxysteroid
      dehydrogenase type II, which protects the mineralocorticoid receptor against
      cortisol that binds to the mineralocorticoid receptor like aldosterone. Liddle's
      syndrome is a rare entity and due to a constitute activation of an aldosterone
      dependent protein which triggers the amiloride sensitive sodium channel in the
      kidney. This results in hypokalemic hypertension with suppressed aldosterone and
      renin levels.

PMID- 9244835
TI  - [Physicians' truthfulness in dealing with patients].

PMID- 9244836
TI  - [Tricuspid valve endocarditis. Demonstration of a rare disease exemplified with 3
      case reports].
AB  - BACKGROUND: Endocarditis of the tricuspid valve is a rare form of valvular
      endocarditis and occurs mainly in patients with special risk factors. CASE
      REPORTS: The three case reports demonstrate 3 young patients (age 30 to 37 years,
      2 female and 1 male) with a typical history of those risk factors. The two women
      were intravenous drug addicts and one of them had suffered already an episode of
      tricuspid valve endocarditis several years ago. The man developed his infection
      after implantation of a pacemaker. In all of the three patients the endocarditis
      was due to infection with staphylococci twice staphylococcus epidermidis and once
      staphylococcus aureus. In two of the three patients the endocarditis could not be
      cured by intravenous antibiotics alone and these patients had to undergo cardiac
      valvular surgery. All patients left the hospital after several weeks without
      signs of infection. CONCLUSION: In clinical praxis the introduction of a special
      endocarditis service, a small team which has to be consulted in every suspected
      case of endocarditis, seems to be beneficial as well as the use of the Duke
      criteria for diagnosis in those cases.

PMID- 9244838
TI  - [Quality in hospital treatment. How is it assured and who determines the
      guidelines?].
AB  - BACKGROUND: Internal quality control of medical performance in the interest of
      patient safety is not a new idea. In fact it has been implemented in varying
      degrees since the beginnings of medicine. ACTUAL SITUATION AND METHODS: Ever
      since hospitals are compelled by law to apply methods of quality assurance and
      external quality control, the question arises as to whether this law can achieve
      a concrete increase in quality of patient care or whether it rather serves to
      support economically motivated goals of health care policies, in the sense of an
      increase in efficiency of performance by physicians. Seen in the light of the
      overall situation of hospital care, the attempt to create mandatory quality
      standards is problematical. A reduction of hospital beds and a decrease in the
      average length of hospital stay contrasts the growing number of treated patients.
      This presents a problem which must be compensated for, despite cutbacks in budget
      and personnel. Methods of quality analysis are of the implicit as well as of the
      explicit type. Implicit methods are based on retrospective data analysis lacking
      previously set standards of comparison. These methods harbor the danger of viewer
      dependent subjectivity (restricted reliability). Explicit methods are based upon
      comparison to previously defined standards. These methods are more objective, but
      often fail to give consideration to individual situations (restricted validity).
      The infrastructure necessary in order to sensibly apply quality control in the
      hospitals is not yet present in Germany. The software required in order to record
      and analyse data is still in a stage of development in many places. CONCLUSION:
      It is of importance not to leave external quality control to politicians and
      economists unfamiliar with the subject matter, but rather that quality control is
      implemented by experts in the medical field.

PMID- 9244837
TI  - [Myoclonus resulting from high-dose epidural and intravenous morphine infusion].
AB  - BACKGROUND: Myoclonus is a possible side effect of opioid therapy, and have been
      described following systemic as well as spinal application. CASE REPORT: We
      report the case of a patient with metastatic carcinoma of the rectum who
      developed myoclonus following administration of high-dose epidural combined with
      iv morphine. This complication occurred with maximum daily doses of 300 mg
      epidurally and 80 mg intravenously and disappeared completely after dose
      reduction. Treatment trials are presented, the pathophysiology of the myoclonus
      is discussed. CONCLUSION: For treatment of opioid-induced myoclonus a dose
      reduction or a change of the opioid should be considered as well as symptomatic
      treatment with benzodiazepines or baclofen.

PMID- 9244839
TI  - [Growth and thalassemia].

PMID- 9244840
TI  - [Height percentiles of children at 6 to 11 years of age in the area of Lazio].
AB  - BACKGROUND: In this paper we present growth height standards obtained by an
      auxological study on a primary school population of central Italy (Lazio), in the
      1991-1992 and 1992-1993 school-years. METHODS: 4,175 children were included in
      the study: 2,024 females and 2,151 males, aged from 6 to 11 years. The sampling
      rate corresponds to more than 98% of the total primary school-population of the
      areas mentioned. The statistical analysis of the collected data was carried out
      by the Dipartment of Statistics of the University of Rome, using the widely
      available statistics packages STAT-GRAPHICS and SAS. RESULTS AND CONCLUSIONS: The
      analysis of height mean and standard deviation showed an increasing trend of
      height related to age, without significant differences by sex. The mean heights
      for females and males were practically the same in each age class. Height
      variance increases with age, too. This fact necessitates the use of the weighted
      regression technique to evaluate the functions that express the height growth
      trend. The relationship between height and age is linearlike and almost coincides
      for the two sexes. The height percentiles were calculated and the relative curves
      were developed, based on the distribution of normalized residuals. The centile
      curves confirm that there are no significant differences in the growth trends for
      both sexes and therefore the lines are overlapping. Substantial differences exist
      only in the end centiles (3th and 97th) and age extremes (6 and 11 years),
      possibly because of the small number of subjects.

PMID- 9244841
TI  - [Knemometry in the assessment of short term effects of growth hormone therapy in
      children with several growth disorders].
AB  - BACKGROUND: Knemometer is a non invasive device for measuring the leg length and
      evaluating statural variations otherwise not disclosed by means of Harpenden
      stadiometer. In several clinical conditions of short stature, knemometer allows
      to evaluate the short-term effect of growth promoting agents, as well as the role
      of infections on growth dynamics. METHODS: The short-term (37-56 days)
      variability of the leg length in subjects with isolated growth hormone deficiency
      (1 case), Turner syndrome (2 cases) and Silver-Russel syndrome (1 case) treated
      with rhGH have been evaluated. The measurements were performed weekly by the same
      operator, at the same weekday and daytime. RESULTS AND CONCLUSIONS: The results
      show a correlation between intercurrent illnesses and growth failure, as well as
      a growth resumption at the end of the former, despite the etiology of short
      stature. Growth hormone treatment seems to exert an influence on growth only in
      the subject with GH deficiency, whereas a similar short term effect is not found
      in the cases of Turner syndrome and Silver Russel syndrome. This fact suggests
      that, also by knemometry, a most prolonged follow-up is required to evaluate the
      effect of GH on short term growth.

PMID- 9244842
TI  - [Neurofibromatosis I: a clinical series and genetic correlations].
AB  - Type 1 neurofibromatosis represents 90% of all forms of neurofibromatosis. It is
      a disease with an incidence of 1:3000 neonates with a dominant autosomic form of
      transmission, but 50% of all cases are sporadic owing to new mutations. Diagnosis
      is mainly clinical and requires at least of the following signs: CAL,
      neurofibromas, glioma of the optic nerve, axillary lentigo, Lisch's nodules, bone
      lesions and the presence of the disease in at least one first-degree relation.
      These criteria may also be applied in children under 6 years old as is confirmed
      by the clinical series of 5 cases referred to our attention. The deletion of the
      long arm of chromosome 17 in the zone proximal to the centromere containing the
      gene of type 1 neurofibromatosis was observed in one case. The phenotype of this
      subject was correlated to another 5 cases reported in the literature.

PMID- 9244843
TI  - [Lipid pneumonia. Favorable outcome after treatment with intravenous
      immunoglobulins, steroids, cephalosporins].
AB  - Lipoid pneumonia. Recovery after treatment with intravenous immunoglobulins,
      steroids, cephalosporins. A case of lipoid pneumonia is described, due to
      accidental inhalation of cosmetic oil occurred in an infant 11 months old, which
      caused severe clinical and radiological features. The patient was treated with
      antibiotics, corticosteroids and intravenous immunoglobulins. Clinical and
      radiological recovery was achieved within 5 months and persisted at 9 and 20
      months follow-up.

PMID- 9244844
TI  - [Comment on neonatal growth standards. Letter].

PMID- 9244845
TI  - Inflammation, aspirin, and the risk of cardiovascular disease.

PMID- 9244846
TI  - Inflammation, aspirin, and the risk of cardiovascular disease.

PMID- 9244847
TI  - Inflammation, aspirin, and the risk of cardiovascular disease.

PMID- 9244848
TI  - Inflammation, aspirin, and the risk of cardiovascular disease.

PMID- 9244849
TI  - Hepatitis-associated aplastic anemia.

PMID- 9244850
TI  - High-dose pulsed dexamethasone for immune thrombocytopenia.

PMID- 9244851
TI  - Stenting for carotid stenosis.

PMID- 9244852
TI  - Stenting for carotid stenosis?

PMID- 9244853
TI  - Osteomyelitis.

PMID- 9244854
TI  - Osteomyelitis.

PMID- 9244855
TI  - Cellulitis due to botfly larvae.

PMID- 9244856
TI  - High intracellular calcium levels during and after electrical discharges in
      molluscan peptidergic neurons.
AB  - Intracellular calcium levels ([Ca2+]i) during and following electrical activity
      of the neuroendocrine caudodorsal cells of the pond snail (Lymnaea stagnalis)
      were measured in situ and is dissociated cells by combining electrical recordings
      and Fura-2 measurements. Caudodorsal cells are typical neuroendocrine cells that
      control egg laying via the release of a set of peptides during a stereotyped
      discharge of action potentials. Single action potentials or short trains of
      spikes in dissociated caudodorsal cells induced only small but consistent
      increases in [Ca2+]i. With longer or repeated spike trains, larger [Ca2+]i
      transients were measured, indicating accumulation of calcium. The calcium channel
      blocker Ni2+ suppressed the calcium elevation, suggesting that calcium influx
      occurred through voltage-activated calcium channels. Calcium levels in
      caudodorsal cells in situ were measured before, during and after the stereotyped
      firing pattern, a approximately 35-min discharge of regular spiking. Basal
      calcium levels in caudodorsal cells in situ were about 125 nM. During the initial
      phase of the discharge, the intracellular calcium level increased to
      approximately 250 nM. Maximal calcium levels (300-600 nM) were only reached at
      the final phase of the discharge or several minutes after the cessation of
      firing. Calcium levels remained elevated for up to 1 h after the end of the
      discharge. During this time, caudodorsal cells were characterized by very low
      excitability. We suggest that the prolonged, elevated level of calcium following
      the discharge need not be directly dependent on action potentials. The long
      lasting [Ca2+]i elevation may cause the release of neuropeptides to outlast the
      duration of electrical activity, thus uncoupling release from spiking. In
      addition, it may cause reduced excitability of neuroendocrine cells following a
      period of spiking, thereby inducing a refractory period.

PMID- 9244857
TI  - [Myocardial infarct and diabetes mellitus: incidence, management and prognosis].
AB  - The authors analyse the data of the Myocardial and Diabetes Register, where 2436
      diabetic patients (pts) and 1448 pts with acute myocardial infarction (AMI) were
      registered between 1st of January, 1992 and 31st of December 1994. In the history
      of diabetic patients previous AMI was present in 14.4% of the cases. The 21.6% of
      the AMI pts had diabetes mellitus as well. According to the type of diabetes
      (IDDM and NIDDM) the prevalence of AMI in the history of the registered persons
      was significantly different: among pts with NIDDM the previous AMI was found
      14.8% of the pts and only 2% of pts with IDDM (p = 0.012). The clinical picture
      of AMI was also different of AMI pts with and without diabetes: chest pain
      suggesting AMI was present 10.9% of pts with proved AMI and diabetes mellitus,
      and 86.2% of pts with AMI without diabetes (p < 0.0001). The Streptokinase
      treatment was more common among AMI pts without diabetes (18.2% versus 12.5% p =
      0.022). The hospital lethality was significantly higher among AMI pts with
      diabetes (42.8% versus 29.4% (p < 0.0001). The poorer prognosis was independent
      of age.

PMID- 9244858
TI  - [Follow-up of high risk, human papillomavirus (HPV)-positive patients with cancer
      of the uterine cervix].
AB  - The study population consisted of 30 cervical cancer patients stage I.a-II.b.
      (FIGO) stages operated on according to the Wertheim technique. A parallel
      histological evaluation and HPV status determination were carried out on biopsies
      from the primary tumors and on the regional lymph nodes. A general primer
      mediated polymerase chain reaction (PCR) was performed at first and the samples
      not amplified were examined by type-specific primers. All except one primary
      tumors contained DNA-sequences characteristic for high risk HPV-types. The lymph
      nodes of these HPV-positive patients proved to be also HPV-positive with a
      frequency of 25/30 (83%). The frequency of the HPV-positivity was higher (100%)
      in the group of patients with HPV-18 positive status, than in the HPV-16 positive
      group. Two thirds of the evaluated regional lymph nodes were HPV-positive in the
      HPV-16 group of patients. The same HPV-types were harboured by the primary tumors
      and by the regional lymph nodes both in the HPV-16 positive and HPV-18 positive
      groups of patients. In the HPV-16-positive group of patients metastatic lymph
      nodes occurred with a frequency of 3/16, while the frequency of HPV-16 positivity
      in the same nodes was 11/15. In the group of patients with HPV-18 positivity the
      difference was even greater, 1/12 v. 12/12. Early recurrences were detected in a
      relation of 3 to 1 in the group of patients with histologically tumor-free and
      metastatic-positive lymph node status. At the same time all of the lymph nodes in
      this group with early recurrency (4/4) contained DNA-sequences characteristic for
      the HPV-18 type. These findings raise the hypothesis that the HPV-specific
      nucleic acids detected in the lymph nodes can be taken as sensitive indicators of
      metastases. The follow-up results support these hypothesis as patients with HPV
      18 positive lymph node status showed early recurrencies and short survival that
      is poor prognosis not corresponding to the early stage of cervical cancer with
      histologically negative lymph node status.

PMID- 9244859
TI  - [The ursodeoxycholic acid-p-aminobenzoic acid test in the diagnosis of small
      bowel bacterial overgrowth syndrome].
AB  - Contaminated small bowel syndrome is frequently associated with meteorism due to
      excessive gas formation, and diarrhoea as a result of bacterial fermentative
      processes, including splitting of carbohydrates or deconjugating and
      dehydroxylating bile salts. In addition to gas production, bacteria capable of
      metabolizing bile salts have been shown to release p-aminobenzoic acid (PABA)
      from and Ursodeoxycholic-acid-PABA substrate. Our aim was to determine the
      possible complementary role of the UDCA-PABA test in the diagnosis of bacterial
      overgrowth. PATIENTS AND METHODS: The H2 breath and UDCA-PABA tests were
      performed simultaneously on 46 patients with suspected contaminated small bowel
      syndrome, and on 7 healthy subjects. The H2 breath test was performed by oral
      loading of 25 g lactose and/or 10 g lactulose. The UDCA-PABA test was carried out
      by determining urinary excretion of PABA after oral loading with 250 mg UDCA-PABA
      conjugate. The diagnosis of bacterial overgrowth was established, when either H2
      breath, or UDCA-PABA test proved to be pathological. RESULTS: Based upon the
      pathologic values of either the H2 breath test, or the UDCA-PABA test, 25 out of
      46 patients proved to have contaminated small bowel syndrome. In 10 out of 25
      patients only pathologic urinary PABA excretion (12.772 +/- 1.707 vs 4.1 +/-
      0.58), indicated bacterial overgrowth, and in 9 out of the same group only
      positive H2 breath test (early rise of > 20 ppm of H2) indicated the same, while
      in 6 cases both tests proved to be pathological. In 7 CSBS patients the urinary
      excretion of PABA significantly decreased following a 10 day Tinidazole treatment
      (5.48 +/- 1.286 vs 13.068 +/- 2.068). CONCLUSION: The UDCA-PABA test proved to be
      a valuable complementary method to detect bacterial overgrowth, when H2
      production failed to reveal bacterial overgrowth.

PMID- 9244860
TI  - [Diagnostic value of tumor markers in ENT oncology].
AB  - Control serum samples of young, healthy volunteers (N = 5) were compared with
      serum samples and laryngeal cancer extracts of patients (N = 12) with stage 3 and
      4 cancers. Eight patients were primarily treated by total laryngectomy, 4 patient
      by palliative irradiation therapy (60 Gy). Ethanol (80%, pH 2) extracts of sera
      and cancer specimen were gel chromatographed, and the nominally 0.3-5 KDa
      molecular mass substances were further examined by analytical capillary
      isotachophoresis (ITP) (LKB. Sweden). Serum samples were also examined after
      surgery of irradiation therapy. Serum and tumor extracts of each laryngeal cancer
      patient contained a substance in the molecular mass range of 0.3-5 kDa. This was
      not detected in the serum of normal control subjects. The marker-candidate
      substance disappeared from the serum of four out of 8 laryngectomized patients
      who live tumor-free for years. Recurrence or lymph node metastasis developed in
      three of the remaining four patients who did not become free of the marker
      substance after laryngectomy. The concentration of the marker has been increased
      in the serum after palliative irradiation in all four patients. This marker
      substance is probably a product of tumor necrosis. The marker may adequately
      monitor the recurrence of tumor postoperatively of after irradiation therapy.

PMID- 9244861
TI  - [Systemic mastocytosis].
AB  - The systemic mastocytosis is a rare disorder, however, the authors recently
      diagnosed two cases causing diagnostic problems. The diagnosis was proved by bone
      marrow biopsy in both patients. The authors review the diagnostic pathway
      considering the pitfalls. According to their conclusion, the most important
      factor in the diagnosis of systemic mastocytosis is to think of the possibility
      of systemic mastocytosis.

PMID- 9244862
TI  - [Hungarian connection of decompression surgery for endocrine orbitopathy].

PMID- 9244863
TI  - [Life and diseases of Luther and the renaissance popes].

PMID- 9244864
TI  - Oncology nurses fill roles as nurse coordinator/case manager.

PMID- 9244865
TI  - Order sheets help prevent chemotherapy administration errors.

PMID- 9244866
TI  - Guidebook helps patients on their journey through transplantation.

PMID- 9244867
TI  - Patients and caregivers benefit from transplantation classes.

PMID- 9244868
TI  - Day hospital improves quality of life for patients undergoing transplantation.

PMID- 9244869
TI  - [Significance of adhesion molecules in oncology].
AB  - Cell-Cell-and cell-extracellular matrix interactions are important in the process
      of tumor cell invasion and metastasis. These interactions are mediated by
      adhesion molecules e.g. CD44, integrins, E-cadherin and N-CAM. The role of
      adhesion molecules along metastatic cascade as well as their importance in tumor
      differentiation and progression are discussed herein.

PMID- 9244871
TI  - [Regression grading of neoadjuvant non-small-cell lung carcinoma treatment].
AB  - In the scope of a multi-center-study 35 resection specimens from patients with
      locally advanced non-small cell lung cancer after neoadjuvant chemotherapy and
      radiation were processed histologically and graded according to the following
      regression grading system: grade I: no or only slight, in general spontaneous
      tumor regression, grade IIa: incomplete tumor regression with more than 10% and
      grade IIb less than 10% vital tumor tissue as well as grade III: complete tumor
      regression. In 15 patients with grade II a to III tumor regression roughly
      concentric foci of various size with a sequence of central tumor necrosis, narrow
      foam cell rim, vascular granulation tissue and peripheral scar formation were
      demonstrated as characteristic feature of response to neoadjuvant therapy. In
      patients with grade IIb to III tumor regression ("responders") median survival
      time of 27.9 months was significantly longer than in patients with grade I to II
      a tumor regression ("non-responders") with a median survival time of 12.7 months.

PMID- 9244870
TI  - [Incidence and prognostic significance of epithelioid cell reactions and
      microcarcinoses in regional lymph nodes in stomach carcinoma].
AB  - The frequency and prognostic relevance of sarcoid-like lesions and
      microcarcinosis in regional lymph nodes in gastric cancer (n = 113; pT1-3, pN0-1,
      pM0, R0) were investigated; the prognostic value was compared with pT and pN
      stage, grading and Lauren's tumor classification with Cox's multivariate
      regression-model. Sarcoid like lesions were found in 34% of the cases (n = 113).
      Statistical analysis did not indicate that they had any prognostic value or
      showed whether or not microcarcinosis or metastasis was present; they were
      independent of pT stage, histological tumor type, tumor grading, and the clinical
      course of disease. Microcarcinosis (defined as scattered carcinoma cells within
      lymph node sinuses or pulp without adjacent stromal reaction) was revealed by
      immunohistochemistry in 90% of pN0 cases; the presence of 3 or more tumor cells
      per lymph node section in over 10% of sampled lymph nodes per case carried a
      significant prognostic value. In microcarcinosis without evidence of metastasis,
      the number of tumor cells and the number of involved lymph nodes are of
      prognostic value. In pN1 cases microcarcinosis was found as well as the
      metastases in 97% and had no additional prognostic value. Microcarcinosis alone
      has a different significance from lymph node metastasis for prognosis.

PMID- 9244872
TI  - [Primary salivary gland tumors in lymph nodes of the parotid gland. Report of 3
      cases and review of the literature].
AB  - Multiple intra- and paraglandular lymph nodes develop in the parotid gland,
      including salivary gland tissue with acinar and ductal formations. In the same
      way heterotopic salivary gland tissue can be localized in cervical lymph nodes.
      Except for the frequently occurring Warthin tumours, primary salivary gland
      tumours, which develop in the lymph nodes of the parotid gland or the cervical
      lymph nodes, are rare. Examples of these are adenomas (pleomorphic adenoma, basal
      cell adenoma) and carcinomas (acinic cell carcinoma, mucoepidermoid carcinoma,
      sebaceous gland carcinoma). Three of our own observations (sebaceous
      lymphadenoma, acinic cell carcinoma, mucoepidermoid carcinoma) are analysed. The
      condition for the diagnosis of primary salivary gland tumour within a lymph node
      is reliable evidence that the salivary gland tissue is tumour-free and that no
      other occult carcinoma is present.

PMID- 9244873
TI  - [Lymphoepithelioma-like lung carcinomas].
AB  - Having observed 2 cases of lymphoepithelioma-like carcinoma of the lung in a 49
      year-old female and in a 66-year-old male patient, we present a review on this
      entity, which was described for the first time in 1987. Essentially this neoplasm
      has the same histological appearance as a Schmincke-Regaud tumor, but it is
      possible that a certain morphological variety exists. In the differential
      diagnosis, a metastasis of a Schmincke-Regaud tumor and a malignant lymphoma
      should be considered. Including our 2 cases, a total of 30 cases have been
      reported: 14 male patients aged between 33 and 73 years and 12 female patients
      between 38 and 70 years; in 4 cases there was no reference to sex or age. Most of
      the patients were Asians, mainly Chinese. These tumors presented with nearly the
      same frequency in both lungs. They mostly appeared as peripheral coin lesions in
      the chest X-ray study. Lymph node metastases were found in approximately 25% of
      the cases. Hematogenous metastases seldom occurred and were observed almost only
      in the skeletal system. In most cases a lobectomy was performed. At present, no
      exact assertion is possible regarding the prognosis. An association with an
      Epstein-Barr virus infection was observed in the Asian patients, but not in the
      Caucasian patients.

PMID- 9244874
TI  - [TNM--current status. 1. Clinical significance and current status].

PMID- 9244875
TI  - [Genetic studies of differential fatty tissue tumor diagnosis].
AB  - Adipose tissue tumors are often characterized by typical or even specific
      chromosomal alterations. In some of the cases the molecular background of these
      microscopically visible alterations was already elucidated. In myxoid
      liposarcomas the translocation t(12;16) creates a fusion gene between the CHOP
      gene and the FUS gene and in lipomas the HMGI-C gene becomes rearranged by
      structural aberrations involving chromosomal region 12q14-15. Based on examples
      of a lipoma, a well-differentiated liposarcoma, a myxoid liposarcoma, and an
      aggressive angiomyxoma it is demonstrated in the present paper how cytogenetic
      investigation can be used as an additional tool for an improved diagnosis of
      adipose tissue tumors. Furthermore, the detection of molecular mechanisms
      underlying the visible cytogenetic alterations will certainly significantly
      increase our knowledge about the pathogenesis of these diseases.

PMID- 9244876
TI  - [Myocardial pump failure in dilated cardiomyopathy and pheochromocytoma].
AB  - Progressive dyspnoea developed in a 37-year-old woman over a period of 2 months.
      A chest x-ray and echocardiography revealed a massive dilatation of the heart
      with thrombi in both ventricles. The endomyocardial biopsy was classified as
      myocarditis in two different departments of pathology. The patient developed
      thromboembolic events and an untreatable heart failure which led to the patient's
      death. The necropsy revealed a dilated 600-gram-heart and thrombi in both
      ventricles. On histological and immunohistological examination of the heart, the
      original diagnosis was corrected to catecholamine-induced dilated cardiomyopathy.

PMID- 9244877
TI  - [Ectopic meningioma in the tonsil].

PMID- 9244878
TI  - [Distribution of reimbursement based on federal and regional data. Emphasis:
      Pathology in the first quarter of 1996. Presentation at the Meeting of the Board
      and Directors of the Professional Society of German Pathologists e.v. 9 November
      1996 in Dusseldorf].

PMID- 9244879
TI  - [100 years of the German Society of Pathology (1897-1997)].
AB  - The German Society of Pathology emerged from the Society of German Scientists and
      Physicians. Founded in Braunschweig in 1897, the first scientific meeting was
      held in Dusseldorf in 1898. Rudolf Virchow was the first chairman up to this
      death in 1902. From the beginning the Society with its former name of German
      Pathological Society till the 2nd world war, was an association of German
      speaking countries including Austrian and Swiss pathologists who also regularly
      presided at the meetings. Alternately the meetings were held in Germany, Austria,
      or Switzerland. The 100-year-history of the Society has been documented in 80
      volumes of the meetings so far. Since 1903 these are published by Gustav Fischer,
      Jena-Stuttgart. The scientific results of the annual meetings show not only the
      growth and development of Pathology, but also the lectures and papers to the main
      subjects contribute considerably to the history of medical basic research in the
      20th century. The chairmen's speeches combine to a history of problems in the
      subject of Pathology. Rudolf Virchow began it with his opening address in 1898. A
      special chapter covers the period of national socialism and German partition
      after the 2nd world war. The German Pathological Society suffered great losses by
      dismissal and emigration after 1933. Institutes rich in tradition got lost in
      East Germany. The partition of Germany, especially after construction of the
      wall, excluded the East German colleagues for Society life. An attempt has been
      made to record the losses in numbers by evaluation of the member lists of the
      meeting volumes. At the end of the century and after overcoming of the German
      partition, the German Society of Pathology has got a chance for revival.

PMID- 9244880
TI  - [The German Society of Pathology on the threshold of its second century].

PMID- 9244881
TI  - [One hundred years of German neuropathology].
AB  - The history of the German Neuropathology since the beginning of the 20th Century
      with its roots in psychiatry, neurology, and pathology and with its
      interconnections in these specialties til today is demonstrated. The changes in
      methods and in main scientific topics are mentioned just as the shadows fallen
      after a flower time in the first three decenniums in the international reputation
      by the expulsion into the emigration and the political persecution of so many
      colleagues, furthermore by the involvement in the so-called euthanasia. The
      institutional development since 1945 lead to the foundation of an own scientific
      society, own congresses, and a regulated training as the basis to win again
      international acceptance. Risks will be seen in the overspecialization as well as
      in the uncritical adaptation of molecular genetic methods.

PMID- 9244882
TI  - [History of the Swiss Society of Pathology. A fragment].

PMID- 9244884
TI  - [Theoretical pathology].

PMID- 9244883
TI  - [Pathology in Austria].

PMID- 9244885
TI  - [Control and development of breathing, pathophysiological aspects].
AB  - The respiratory control system guarantees acid-base-homeostasis as well as the
      rhythmic activities of the respiratory motor system in accordance with exercise
      and behavioural programmes of the human being. Cortical patterns and synchronized
      respiratory patterns with tracheal flow and pressure variations in the fetus
      indicate the common network of respiration and sleep-wake mechanisms in an early
      stage already. During fetal life acid-base-homeostasis is dependent on
      progesterone controlled mechanisms. CO2 partial pressure of the uterine artery
      reduces to 32 mmHg. The O2 Partial pressure of the umbilical vein is 25-30 mmHg
      only. The raise of PCO2 during delivery is accompanied by a shower of sensory
      input to the reticular formation causing arousal and the opening of the lungs.
      The continuation of postnatal breathing is the consequence of the integration of
      the central chemosensitive mechanism and the reticular activating system at an
      adequate threshold. Perinatal defense reflexes, functional patterns and
      strategies in early life may outline later pathophysiological mechanisms for
      sleep apnea, apparently life threatening event (ALTE), sudden infant death, and
      congenital central hypoventilation syndrome.

PMID- 9244886
TI  - [PO2-affinity of oxygen-sensitive intracellular signal cascades].
AB  - The oxygen partial pressure field in different organs ranging from 0 to 100 Torr
      is likely to be a mirror of oxygen sensitive intracellular signal cascades
      determining ion channel open probability, metabolic pathway activities and gene
      expression. High or low PO2 affinities of the particular signal cascade optimise
      the oxygen sensitive cellular response for adapting organ functions to variations
      of the oxygen supply conditions. The signal cascades are triggered by an oxygen
      sensor which is believed to be a heme protein. In some cases oxygen radicals are
      acting as second messengers revealing these signal cascades as an evolutionary
      highly conserved principle first described in bacteria.

PMID- 9244887
TI  - [Pulmonary causes of hypoxia in premature infants and its therapeutic
      possibilities].
AB  - Pulmonary illness as a cause of postnatal hypoxia in premature infants frequently
      calls for an extended clinical course. Concealed behind the common symptoms-
      cyanosis, tachypnoea, expiratory grunting, thoracic and/or epigastric retraction
      and nasal flaring--is a broad spectrum of respiratory disorders. Lack of
      surfactant plays the most important role in premature infants, although meconium
      aspiration, persistent fetal circulation, the post asphyxia syndrome, transient
      tachypnoea of the newborn and pneumonias can also be the underlying cause. 1.
      PREVENTION: a. Avoid preterm delivery-b. Induce maturation of the fetal lungs
      (antenatal maternal corticosteroid administration). 2. Treatment of the cause:
      Endotracheal surfactant replacement therapy. 3. Symptomatic treatment:
      Respiratory support, from the simple method of giving oxygen over a mask to
      artificial ventilation. Immature lung tissue can be destracted as a complication
      of artificial ventilation. Here, the cause for the pulmonary hypoxia is
      iatrogenic. The resultant clinical picture of bronchopulmonary dysplasia (BPD)
      can then determine progress of the child for weeks or months to follow. The most
      important measure in the prevention of BPD are, in addition to the prophylaxis
      and treatment of the causes of respiratory disorders in preterm infants, the
      skilled resuscitation in the labor ward, and most important of all, the gentle
      handling and loving care for the tiny premature baby.

PMID- 9244888
TI  - [Postnatal development of breathing control].
AB  - Respiratory movements already occur in the fetus together with low amplitude high
      frequency EEG. During birth external stimuli drive respiration, supported by the
      development of hypercapnia, hypoxia and acidosis. The thresholds of the
      chemosensitive systems adapt during the first hours and days of life (CO2
      sensitivity) or weeks (hypoxic sensitivity). In 180 healthy infants between 5
      days and 18 months of age we performed respiratory CO2-responses during NREM
      sleep and studied the immediate response to inhalation of 60% oxygen (Dejours
      test) as well as in 8 children with congenital central alveolar hypoventilation
      syndrome (CCHS) and 15 infants who experienced an apparently life-threatening
      event (ALTE). Infants older than 2 weeks had a mean PCO2 of 40-42 mmHg, the slope
      of the CO2-response showed no age trend and was found in the range of adults with
      a 22-38% increase in ventilation per Torr increased PCO2. Preterm infants had a
      significant lower CO2-response (16 vs. 33%) until they reached their estimated
      normal birth date. In the ALTE group the CO2-response was suppressed to 17%.
      Children with CCHS did not respond to CO2 by increasing their ventilation, even
      after years. The response to hyperoxia as a measure of peripheral chemoreceptor
      activity decreased from a 31% initial inhibition of ventilation at 1 month to 20%
      at one year. Our results indicate that temporary or lasting reduction or lack of
      the respiratory CO2 sensitivity may cause apneic events or hypoventilation.
      Different slopes of CO2- and hyperoxic responses in very young infants compared
      to older ones favour the occurrence of oscillations in the control of breathing
      such as periodic breathing during sleep.

PMID- 9244889
TI  - [Deterministic-chaotic and spectral-functional analysis of heart rate and
      respiratory movements].
AB  - After an introduction into the analysis of periodical-linear and deterministic-
      chaotic characteristics of heart rate fluctuations and respiratory movements
      their physiological background and clinical aspects are debated. Using the
      example of own results at the mature rabbit and new-born pig different relations
      of periodical-linear and deterministic-chaotic characteristics in dependence on
      the experimental status and neurovegetative blockades are demonstrated. From the
      data assignments of these characteristics are derived.

PMID- 9244890
TI  - [Cardiorespiratory coupling in obstructive sleep apnea (OSA)].
AB  - Even if different mechanisms of various interactions during sleep are known, it
      is still unsolved by which mechanisms physiological reactions during sleep may
      start a pathophysiological course. Hypoxia, Hypercapnia and repetitive
      sympathetic elevations are well known elements in the control of the arterial
      resistance. Furthermore investigations in patients with sleep apnea showed
      changes of the pulsatile secretion pattern within the renin-angiotensin-system
      and the antinatriuretic peptides. These changes were reversible under nasal CPAP
      therapy, nycturia as a frequent symptom disappeared. Nevertheless neither hypoxia
      nor intrathoracic pressure changes nor the arousals can assert the longterm
      influence on the blood pressure alone, a multifactorial confluence must be
      assumed. Further it is unclear how a tonic increase of the arterial blood
      pressure may occur in dependence of the REM- and NREM-sleep cycle changes as well
      as during daytime. First investigations in sleeping man seem to indicate, that a
      disturbance of the physiological coupling of breathing and circulation may
      present a pathogenetic element. Finally it remains open, whether the changes of
      the cardiorespiratory coupling during sleep of control persons and of patients
      with OSA are comparable, and whether they may be procured for an explanation of
      the pathogenesis of arterial and pulmonary hypertension. Further investigations
      in the control mechanisms of breathing and circulation related to the circuits of
      chemo- and baroreception, thresholds during wakefulness and sleep may be of
      decisive help to process the question, to what extent clinical states find a
      correlate in a disturbed cardiorespiratory coupling and, much more significantly,
      whether a disturbance in the physiological cardiorespiratory coupling appears
      already in early states of a disease. Sleep with ist complex physiology as well
      as with its characteristic pathophysiological phenomenon of sleep related
      breathing disorders has opened a new interdisciplinary field where tools like the
      polysomnography and electronic data analysis are used by physiologists,
      pathophysiologists as well as by physicians.

PMID- 9244891
TI  - [Chronobiology of the bronchial system].
AB  - Control of breathing, bronchomotor tone and lung function are inferior to
      circadian rhythms, which can already be demonstrated at healthy subjects. They
      get relevant especially at patients with obstructive airway disease and sleep
      disturbances. Particularly in the early morning hours flow resistance in the
      airways and in the nose rises. Several different mechanisms are suspected to be
      responsible: Allergen exposure in bed, supine position, interruption of the
      bronchodilator therapy, gastro-oesophageal reflux, tenseness of the airways and
      secretory accumulation. Connected to nocturnal asthma might also be an increased
      airway responsiveness. Several factors contribute to nocturnal asthma, but they
      don't constitute a general concept for the explanation of nightly exacerbations.
      Many hormonal neural cellular and humoral factors show diurnal fluctuations which
      favour a constrictive bronchial response in the night. Diurnal or ultradian
      changes in O2 and CO2 sensitivity only play a minor role. However, we have to
      realise alterations in the responses of the central neuronal control mechanisms
      of breathing within the respiratory cycle. Oscillations of arterial CO2 partial
      pressure or pH-values influence tidal volume and ventilation directly. Circadian
      changes of different vital functions cause minor alterations in airway
      responsiveness and airway resistance in normal subjects, however in patients with
      asthma they are enlarged in amplitude and become relevant especially in the night
      and early morning hours.

PMID- 9244892
TI  - [Asthma and sleep in children].
AB  - Nocturnal asthma-especially night cough are sometimes the first and only symptom
      of the beginning disease in childhood and are then often misinterpreted. The
      cause of nocturnal asthma seems to be a circadian rhythm of hormones and
      mediators, much more predominant in asthmatic than in healthy children. Moreover,
      there are some evidences, that also other factors--i.e. inflammation, number of T
      helper cells and beta-receptors, allergen contact a.o.--influence this process
      leading to a deterioration of bronchial reactivity and lung function. Furthermore
      children with stable asthma show a prolonged expiration time during sleep
      compared to healthy children. Nocturnal asthma calls for an intensification of
      therapy. Besides the removal of allergen sources (HDM) and a warranty of free
      upper airways (adenoids), drug therapy should be optimised. This applies for the
      basic antiinflammatory treatment as well as for the use of long acting
      bronchodilators. The relatively high demand for beta-agonists in children and the
      age dependence of half-life for theophylline must be considered.

PMID- 9244893
TI  - [Respiratory function diagnosis during sleep: possibilities and limitations].
AB  - Diagnosis of the respiratory function during sleep is based on a continuous
      recording of all necessary signals. These are basically respiratory flow,
      respiratory effort and blood gases. In addition, sleep stages, body position and
      cardiovascular function have to be monitored to distinguish the different forms
      of sleep related breathing disorders as there are obstructive, mixed and central
      apnea and hypoventilation. The main evaluation is a simple counting of events and
      the calculation of an index related to total sleep time. These indices are of
      limited value because all information about the duration of the events is lost
      and about the severity which depends on the actual blood gas values. A computer
      assisted evaluation of respiration can overcome these limitations and allows to
      evaluate sleep stage dependencies in addition. Based on the duration of
      respiratory events only it was possible to distinguish patient groups which also
      provided different blood gas values at daytime. Determination of the critical
      closing pressure of the upper airways during sleep can help to quantify effects
      of body weight loss and other therapeutic interventions beside ventilation
      therapy in patients with sleep related breathing disorders. Quantitative
      characterisation of respiration during sleep is limited by the fact that most
      methods available induce changes in sleep or respiration itself. A study on
      healthy subjects proved an increased number of arousals during cardiorespiratory
      polysomnography. Therefore the added value obtained by quantitative methodology
      (pneumotachograph and esophageal pressure) must be weighted against non-invasive
      technology (inductive plethysmography). Non-invasive methods can provide
      comprehensive information about the respiratory function, especially if extensive
      computer-assisted evaluation is used. These evaluations still need further
      improvements. Nevertheless they can help to clarify the different types of
      respiratory regulation present in NREM-, REM-sleep and awake state.

PMID- 9244894
TI  - [Current concepts and techniques in home ventilation therapy].
AB  - Home ventilation of spontaneous breathing during wake and chiefly during sleep
      has gained great importance in the last 10 years by means of noninvasive nasal
      pressure support ventilation (PSV). Intensive care and weaning has been
      complemented, or even replaced by this method. Self-adaptive machines are already
      available for about 2 years. Historical development is outlined, contrasted by
      the actual procedures, their advantages and disadvantages. Long term therapy
      implies functional and probably even morphological adaptation of spontaneous
      control of breathing which is briefly touched, according to recent
      investigations.

PMID- 9244895
TI  - [Breath condensate as a method of noninvasive assessment of inflammation
      mediators from the lower airways].
AB  - The detection of mediators from the lower airways still depends on invasive or
      provoking sampling techniques like bronchoalveolar lavage (BAL) or induced
      sputum, respectively. Both methods affect the specimen itself. In contrast, the
      breathing condensate opens the possibility to get native specimens from lower
      airways during breathing at rest. The breathing condensate was obtained by
      freezing of exhaled air. The equipment was developed in the FILT Res. Soc. Ltd..
      The method is applied for a patent. Leukotriene B4 and Leukotriene C4D4E4F4 were
      measured in the exhalation of asthmatics, patients with different airway
      disorders and healthy volunteers. In an additional study the condensate was
      obtained before and after of a non-specific bronchial challenge test. In
      asthmatics a close correlation between leukotriene concentration of the
      condensate and the degree of asthmatic disease according to "International
      Consensus Report" was found, but no correlation to lung function tests. Within a
      bronchial challenge test applying histamine the release of leukotrienes was shown
      to be more sensitive to the challenge test than a lung function test. The results
      of the study indicate new diagnostic possibilities in lung diseases using the
      detection of non volatile substances in the exhaled air.

PMID- 9244896
TI  - [Differentiated characterization of pulmonary diffusion].
AB  - The results of Single-Breath-Test with carbon monoxide offers only a rough
      estimation of the gas exchange situation in the lung as concerns pulmonary
      diffusion capacity. This statement is related to overestimation of diffusion
      capacity and reduced possibility to characterize disturbances of pulmonary
      diffusion function on the basis of values assessed. The proposed six-array
      diagram offers the possibility to characterize the disturbances of diffusion more
      exactly and to differentiate them simultaneously regarding the values determined.
      So it is possible, to characterize better structural changes of the blood-gas
      barrier of the lung and to demonstrate compensatory mechanisms.

PMID- 9244897
TI  - [Relationship between respiratory reserve in the flow-volume curve and the
      expected ergometric capacity].
AB  - To evaluate the physical work capacity in patients with chronic obstructive lung
      disease (COLD) it was checked, if determination of breathing reserve can replace
      the exercise test with blood gas analysis. In 28 patients with lung disease and 7
      healthy subjects the flow-volume-curve under resting conditions and during the
      forced breathing maneuver to measure the breathing reserve and the exercise test
      with blood gas analysis were examined. A correlation was found between both.
      Therefore, in patients with COLD the determination of breathing reserve is a
      practicable method for estimating the physical work capacity, especially in cases
      with absent breathing reserve. Nevertheless, for medical opinion exercise testing
      is necessary.

PMID- 9244898
TI  - [Technical adaptation of impulse oscillometry to special research conditions].
AB  - The technical adaptation of the Impulse-Oscillometry (IOS) to different
      conditions of measurement allows a wide range of applications so that even
      questions of peripheral user groups using lung function tests can be answered.
      Thus, the variable connection of the IOS head via fold hose opens the field of
      bedside measurements and additional applications in pediatrics, intensive care
      and veterinary medicine. Rhinomanometric examinations are possible with little
      expenditure and high practicability using nasal tips.

PMID- 9244899
TI  - [Perspectives of a respiratory function analysis].
AB  - The necessity to develop procedures to assess respiratory functions which are
      independent of collaboration, non-invasive, specific, differentiating and
      sensitive, is stressed. New measuring methods, like main stream detection for
      oxygen and carbon dioxide as well as continuous assessment of pulmonary impedance
      are permissive for this purpose. In addition new characteristic quantities are
      defined. By using these new tools it is shown that the Tiffeneau-maneuver effects
      the properties of the bronchial system substantially. Examples of application
      show clearly that single measurements are not sufficient for characterization of
      the bronchial system. Instead continuous measurement during a certain closed
      period are proposed to get a so-called bronchogram. The increased sensitivity
      possibly makes provocation tests with its risks needless. Experimental results
      reveal longterm instabilities of the bronchial system, which may be discovered by
      a longterm-bronchogram in analogy to a longterm electrocardiogram. A new detector
      for the skin is presented; it allows the determination of an intracutaneous
      oxygen partial pressure as well as the oxygen conductivity of the skin. All
      results offer possibilities of functional analysis as mentioned above.

PMID- 9244900
TI  - [A simple method for improvement of the measurement of respiratory impedance in
      humans by increasing oropharyngeal impedance using cheek and mouth floor clamps].
AB  - It is known, that the upper airway (oropharyngeal) impedance (Z(op)) influences
      the measured input impedance of the respiratory system (Zrs). This investigation
      deals with simple methods reducing the artefact caused by Z(op). The following
      methods have been examined: (1) Supporting the cheeks with fingers, (2)
      supporting the cheeks and the floor of the mouth with fingers and (3) using a new
      mechanical clamp for the cheeks and the floor of the mouth. The effect of these
      procedures on Zrs, were investigated on two subjects. Also Z(op) has been
      estimated during a voluntary closure of the glottis (VALSALVA manoeuvre). The
      impedance has been assessed as well with forced sine shaped oscillations as with
      the pulsatile technique. All three procedures show, compared to measurements
      without any support, an increase of the Zrs, especially at high values. The
      highest increase has been obtained while using the clamp (up to 50%). The varied
      impedance must be placed in parallel to Zrs, because Z(op) increases even more
      than Zrs. So, by applying the clamp the subjects is better coupled to the
      measuring system. The clamp is easy to handle, leads to more exact values, and
      increases the inter- and intra-individual reproducibility.

PMID- 9244901
TI  - [Impulse oscillometry and body position].
AB  - To assess diurnal profiles of impulse-oscillometry (IOS) changes of IOS
      parameters between different body positions have been studied using a special set
      IOS-Bedside for individual home care. IOS has been applied in lateral lying and
      in sitting position in 20 healthy female and male probands, aged 10-67, during 24
      hours in intervals of 3 hours. In each test during normal breathing for
      approximately 30 sec about 130 spectral and structural analyses have been
      performed at an impulse distance of 0.2 sec. The global means of resistance at 5
      Hz (R5) in lying position are in men about 0.6 and in women about 0.3 hPa/l/s
      higher than in sitting position, those of reactance in men and women are only
      about 0.2 hPa/l/s lower. There is a distinct diurnal periodicity of the
      differences. The maxima of them may occur at different hours of the day in single
      probands; but at the average mean the maxima are found at the end of night. The
      differences of oscillation parameters between lying and sitting position are
      bigger at end-expiration than at end-inspiration. The resistance-flow-gradients,
      representing the component of turbulent flow, are enlarged in lying position
      especially at night.

PMID- 9244902
TI  - [Predictability of model size in impulse oscillometric airway resistance
      measurements in animals (calf)].
AB  - The aim of this study was to investigate the behaviour of parameters which can be
      obtained by a 7-component model of the lung using impulse oscillometry in calves.
      Seven healthy conscious calves were examined using "Master Screen IOS" (E. Jaeger
      GmbH & Co. KG, Wurzburg/D) and the following study design: [I] baseline
      measurements, [II] measurements after inhalation saline, [III] measurements
      during carbachol-induced bronchoconstriction, [IV] measurements after
      bronchodilatation by fenoterol. Measurements were made individually using a rigid
      face mask. Examining the spectral behaviour of the respiratory impedance (5 to 35
      Hz), reactance (X) was more sensitive to bronchochallenge (stages [all] and [IV])
      than resistance (R). Using the 7-component model of the lung, the resistance was
      differentiated into a central part (Rz) and a peripheral part (Rp). Changes in Rp
      were more significant than changes in Rz during stages [III] and [IV]. The
      parameters central inertance (Lz), chest wall compliance (Cw), and lung
      compliance (Cl) did not change during the study. Surprisingly, the parameter
      called "bronchial compliance" (Cb) increased significantly during
      bronchoconstriction. Therefore, further research is necessary to clarify whether
      the model needs to be modified for general applications or only for measuring
      bovines.

PMID- 9244903
TI  - [Diurnal profile of impulse oscillometric impedance in healthy subjects].
AB  - Diurnal profiles of impulse oscillometry during 24 hours in 3 hour intervals in
      sitting and lateral lying position have been studied in 20 healthy female and
      male probands 10-67 years of age. Approximating the profiles by a sine-cosine
      function the amplitude of resistance was found up to 3, that of reactance up to 1
      hPa/l/s in single cases, preferably for end-expiratory values and for the
      resistance-flow- and the resistance-volume-gradients, more pronounced in lying
      than in sitting position. The daytime reaching maxima of resistance and minima of
      reactance is different in single individuals. Single persons with obviously high
      vitality or sensibility showed very high amplitudes reproducible within IOS
      measuring limits of 0.2 hPa/l/s after 6 months.

PMID- 9244904
TI  - Plasmid Biology 96: International Symposium on Plasmid Molecular Biology. Graz,
      Austria, September 1-5, 1996. Abstracts.

PMID- 9244905
TI  - The Cerebellum: From Structure to Control. Proceedings of a satellite symposium
      of the Meeting of European Neuroscience. Rotterdam, August 31-September 3, 1995.

PMID- 9244906
TI  - [Power Doppler: physical and constructive principles and comparison with Doppler
      color].

PMID- 9244907
TI  - [High-resolution ultrasonography in the study of carpal tunnel syndrome].
AB  - We investigated the reliability of some US signs in the diagnosis of the carpal
      tunnel syndrome. We carried out a single-blind study with 13-MHz high resolution
      probes and electromyography on 132 patients with clinical evidence of the carpal
      tunnel syndrome; a control group of 20 asymptomatic patients was also submitted
      to US. Eighty-six of 107 patients with US signs of the carpal tunnel syndrome
      were then submitted to surgical decompression (resection of the transverse carpal
      ligament), while the extant 21 patients underwent conservative treatment and
      clinical follow-up. To diagnose the carpal tunnel syndrome, we considered the
      following US patterns: median nerve changes (swelling before its entrance into
      the carpal tunnel and flattening in the tunnel itself), palmar bowing of the
      flexor retinaculum, thickening of the transverse carpal ligament and increased
      depth of the carpal tunnel, as measured from the apex of the transverse carpal
      ligament convexity to the underlying carpal bone. Median nerve changes were
      unreliable signs and were missing in many cases: only 45 of 107 patients
      exhibited median nerve swelling before and/or its flattening in the carpal tunnel
      (42%). Such indirect signs as the thickening of the transverse carpal ligament in
      chronic cases were demonstrated in 94 of 107 patients with the carpal tunnel
      syndrome (88%) and canal deepening in all unilateral carpal tunnel syndromes was
      shown in 92 of 107 patients (87%); both these signs proved to be much more
      reliable. The palmar bowing of the flexor retinaculum was also difficult to
      demonstrate in surgical patients or in those with connective tissue fibrosis
      within the tunnel: this sign was demonstrated in 80 of 107 patients with the
      carpal tunnel syndrome confirmed with electromyography (75%). Tanzer and Rietze
      reported median nerve changes observed at surgery in 43% and 66% of their
      patients, respectively. Recent MR findings in asymptomatic wrists have
      demonstrated that the normal median nerve has an elliptical shape inside the
      carpal tunnel. To conclude, high resolution US exhibited 96% sensitivity, 95%
      specificity and 93% diagnostic accuracy and proved to play a major role in the
      diagnosis of the carpal tunnel syndrome.

PMID- 9244908
TI  - [Normal anatomy and pathologic features of the supraspinatus muscle: comparison
      between ultrasonography and surgery. Analysis of the potential sources of
      diagnostic errors].
AB  - The supraspinatus muscle performs about 60% of the elevation-abduction motion of
      the arm; therefore, it has a prominent functional role among the extrarotational
      muscles of the shoulder and is the most injured in subacromial space conditions.
      Seventy-four patients, aged 21-64 years, were examined to compare ultrasonography
      (US) results with surgical findings in supraspinatus conditions and to analyze
      the possible pitfalls in US diagnosis. All the patients underwent conventional X
      ray, US and then surgery or arthroscopy. The following criteria were considered:
      morphology, thickness, echotexture, the convexity of the superior border of
      supraspinatus tendon, the relationships with the subacromial bursa and the tendon
      of the biceps long head, the regularity of the bone cortex of the humeral head.
      US showed: chronic degenerative tendinopathy in 10 patients; perforating focal
      injuries in 21 patients; deep focal injuries in 10 patients; intramural focal
      injuries in 6 patients; superficial focal injuries in 8 patients; complete tendon
      tear with detachment in 19 cases. 62/74 US diagnoses were surgically confirmed,
      with a specificity of 83.7%. In our experience, US provided very useful
      information about the pattern, size and site of the injuries and was very helpful
      in the surgical planning.

PMID- 9244909
TI  - [Magnetic resonance of the encephalon in 17 patients with ocular Behcet's
      disease].
AB  - Behcet's disease is a chronic relapsing disorder of unknown etiology
      characterized by oral aphthous ulcerations, uveitis, genital ulcerations and bone
      lesions. A variety of other signs including polyarthritis, vascular conditions
      (blood vessel occlusions and aneurysms), epididymitis, gastrointestinal,
      pulmonary and heart lesions may also occur. Central nervous system (CNS)
      involvement is reported in 10-49% of cases and it is the first symptom of the
      disease in 5% of subjects. The neuro-Behcet's syndrome may appear as a brainstem
      syndrome, meningoencephalitis and an organic confusional syndrome or dementia.
      Cranial hypertension, mostly related to cerebral venous thrombosis, is also
      present in neuro-Behcet's disease and its incidence is reported in up to 10% of
      Behcet's patients. MRI is reportedly the most sensitive neuroradiologic approach
      to detect the focal lesions related to neuro-Behcet's disease and several single
      cases or series of Behcet's patients with neurologic signs have been examined
      with MRI. We used MRI to investigate CNS involvement in Behcet's disease patients
      with and without previous neurologic signs. MRI was carried out on 17 patients
      with ocular Behcet's disease without neurologic symptoms to assess the possible
      subclinical involvement of the CNS. Cerebrospinal fluid spaces were enlarged in 8
      patients and 5 patients exhibited cortical atrophy. PD and T2-weighted
      hypersignal foci were demonstrated in parietal, frontal, subcortical and
      periventricular white matter in 6 subjects. Neuroradiologic abnormalities were
      found only in the patients with complete disease and with the disease diagnosed
      more than 10 years earlier. Even though the pathogenesis of these neuroradiologic
      abnormalities and their correlation with Behcet's disease remain to be clarified,
      our study suggests the possibility of subclinical CNS involvement in these
      patients, which may affect the therapeutic approach and their prognosis.

PMID- 9244910
TI  - [Anatomic changes after radical surgery and reconstruction with pedunculated or
      revascularized flaps in advanced head and neck tumors: computerized tomography
      and magnetic resonance findings].
AB  - January, 1992, to October, 1995, sixty-four patients with advanced head and neck
      cancer underwent head and neck reconstructive surgery using myocutaneous or
      revascularized flaps; in the same period, all patients were consecutively
      examined with CT and MRI. Myocutaneous flaps wer used in 26 patients: 12 flaps
      were tubular and 14 linear. Revascularized flaps were used in 38 patients: to
      repair a large defect in 26 patients (14 latissimus dorsi flaps and 12 temporal
      muscle flaps) and to repair an oral damage in 12 patients (5 revascularized
      radial and 7 jejunal flaps). CT and MR images of myocutaneous flaps showed the
      flaps as fatty areas, repairing large surgical defects, hypodense at CT and
      hyperintense at MRI, with no post-contrast enhancement. The postoperative scar
      around the flap exhibited soft-tissue density with slight post-contrast
      enhancement at CT and slightly hypodense on T2-weighted MR images. Post-contrast
      CT and MRI showed slight scar enhancement with no signal changes in the fatty
      component. The appearance of revascularized flaps at CT and MRI depends on the
      characteristics of the structure used to repair the surgical defect: jejunal and
      radial flaps appeared as mostly fatty thickened layers with both imaging methods.
      Temporal and latissimus dorsi flaps are made basically of muscular tissue, fatty
      tissue and occasionally skin (used to repair a mucosal defect): consequently, CT
      showed a structure with mostly parenchymal density in all cases and MRI depicted
      intermediate signal intensity. MRI was useful to detect 12 revascularized jejunal
      or radial flaps thanks to its higher contrast resolution and multiplanar
      capabilities showing even such thin structures as these flaps. Moreover, MRI
      permitted to study skull base reconstruction with revascularized (latissimus
      dorsi) flaps in 5 of our patients.

PMID- 9244911
TI  - [Spontaneous carotid-cavernous fistula: correlations between clinical findings
      and venous drainage].
AB  - We reviewed retrospectively 6 cases of spontaneous carotid cavernous fistulas to
      discuss the differences in clinical findings depending on venous patterns. Orbit
      US was performed in all patients but one and all patients were examined with CT
      and intraarterial digital subtraction angiography (DSA). Orbit US, performed in 5
      patients with ocular signs, showed dilation of the ophthalmic veins, in 3 cases
      bilaterally. CT was performed to demonstrate possible lesions of the orbit apex
      or skull base and showed dilation of the superior ophthalmic vein in 4 patients,
      bilateral in only one case. Moreover, CT detected enlargement of the cavernous
      sinuses in 4 cases (3 unilateral, one bilateral). Dynamic CT, performed in 2
      patients, showed early opacification of both cavernous sinuses. DSA was carried
      out on the basis of clinical data and US and CT findings. It diagnosed carotid
      cavernous fistulas in all cases. The fistulas were bilateral in 3 subjects. In
      all the patients with exophthalmos, conjunctival chemosis and dilated episcleral
      veins, the superior ophthalmic vein was the main venous drainage from the
      cavernous sinus. Only 4 of these patients had abducent nerve palsy; bruit was
      present in 2 cases only. The ocular signs were contralateral to the fistula in
      one patient. In the patient presenting III, IV and VI nerve palsy, the venous
      drainage was direct from the cavernous sinus to pericarotid plexus, pterygoid
      plexus and inferior petrosal sinus; in this case there were no ocular signs. The
      clinical findings of spontaneous cavernous fistulas are caused by the arterial
      supply and, especially, by the venous drainage of the fistula; for the early
      diagnosis and treatment it is important to know that some patients do not exhibit
      the classic triad of symptoms, characterized by pulsating exophthalmos, bruit and
      conjunctival chemosis. Our experience has confirmed that spontaneous carotid
      cavernous fistulas may be characterized by atypical clinical findings, such as
      ocular signs contralateral to the fistula side or palsies of cranial nerves only.

PMID- 9244912
TI  - [Doppler color ultrasonography with contrast media in the study of eye and orbit
      neoplasms].
AB  - We investigated the diagnostic efficacy of the i.v. administration of a
      sonography (US) contrast agent to study eye and orbit tumors at different stages.
      We administered Levovist (Schering), an air microbubble stabilized by fatty acid,
      which is specific for angiographic indications. Baseline color Doppler US was
      performed on 24 selected patients and tumor vascularization patterns were
      classified into three classes. Color Doppler signal enhancement was assessed
      after contrast agent administration and the signal-to-noise ratio (SNR) was
      improved in 70% of cases, which helped identify vascular patterns and improved
      flowmetric accuracy. The Doppler effect was also improved and vascular signal was
      always enhanced. The SNR was improved also by the postcontrast detection of small
      vessels missed on baseline scans. Doppler signal enhancement was proportional to
      precontrast vascularization and depended on tumor size, with poor results in
      lesions < 5 mm. In contrast, vascular signal spots with increased postcontrast
      echogenicity sometimes caused excessive noise affecting the results. No
      correlation was found between signal enhancement and lesion histotype or between
      signal and lesion site. Treated lesions exhibited poorer contrast agent
      enhancement. The examination technique must be accurate and the various
      parameters set optimally, especially the velocity scale, gain and filtration; the
      unit must feature adequate recording capabilities (mm/s). To conclude, we believe
      that the routine use of i.v. US contrast agents will play a major role in
      improving diagnostic imaging in oculistics also thanks to the lack of untoward
      reactions and to the ease of contrast agent preparation.

PMID- 9244914
TI  - [Radiologic assessment in lung volume reduction surgery in emphysema].
AB  - Aim of this work is to present and discuss the radiologic protocol we have
      developed for the preoperative assessment of patients with severe pulmonary
      emphysema candidate to lung volume reduction surgery (LVRS). The operation aims
      at improving respiratory mechanics and reducing small airway obstruction by
      removing variable amounts of emphysematous parenchyma. January to September,
      1996, twelve patients were submitted to LVRS. Before surgery all patients were
      examined with standard chest radiographs during maximal inspiration and
      expiration, chest Computed Tomography (CT), High Resolution Computed Tomography
      (HRCT) and air trapping quantitation on HRCT scans. Diaphragm and chest wall
      excursions, patterns, site and distribution of emphysema, as well as
      heterogeneity (i.e., the uneven distribution of emphysematous and normal
      parenchyma) were investigated. Air trapping was quantitated with a dedicated
      software. Postoperative studies were carried out 2 months later in six patients
      and included: maximal inspiratory and expiratory chest radiographs and air
      trapping assessment on 3 standardized HRCT scans. All parameters considered
      improved in every patient. Radiologic studies proved to be of crucial importance
      for patient selection and LVRS planning. Despite our limited number of patients,
      the diagnostic protocol adopted in our Hospital appears a valuable tool for both
      pre- and post-operative assessment of the patients candidate to LVRS.

PMID- 9244913
TI  - [Quantitative assessment of pulmonary emphysema with computerized tomography.
      Comparison of the visual score and high resolution computerized tomography,
      expiratory density mask with spiral computerized tomography and respiratory
      function tests].
AB  - CT is the most accurate method to detect pulmonary emphysema in vivo. We compared
      prospectively two different methods for emphysema quantitation in 5 normal
      volunteers and 20 consecutive patients with chronic obstructive pulmonary disease
      (COPD). All subjects were submitted to function tests and HRCT; three scans were
      acquired at preselected levels during inspiration. The type and extent of
      pulmonary emphysema were defined, using the time-honored visual score system, by
      two independent observers under blind conditions. Disagreements were subsequently
      settled by consent. All subjects were also examined with expiratory spiral CT,
      using a density mask program, at two different cut-off levels (-850, -900 HU).
      Visual score and expiratory spiral density mask values (-850 HU) were
      significantly correlated (r = 0.86), but the visual extent of emphysema was
      always higher than shown by expiratory spiral CT. The emphysema extent assessed
      with both CT methods correlated with the function result of expiratory airflow
      obstruction and gas diffusion impairment (visual score versus forced expiratory
      volume in one second: r = -0.81, versus single breath carbon monoxide diffusion:
      r = -0.78. Spiral expiratory density mask -850 HU versus forced expiratory volume
      in one second: r = -0.85, versus single breath carbon monoxide diffusion: r = 
      0.77). When -900 HU was used as the cut-off value for the expiratory density
      mask, the correlation with single breath carbon monoxide diffusion worsened (r = 
      0.56). Visual score and expiratory density mask -850 HU gave similar results and
      permitted COPD patients to be clearly distinguished from normal controls (p <
      0.01). Residual lung volume, measured with expiratory spiral CT correlated
      significantly with residual volume measured with the helium dilution technique (r
      = 0.66), but CT values were always higher than function results. We believe the
      true residual volume should lie somewhere in between the CT value and the
      function results with the helium dilution technique and conclude that the extent
      of pulmonary emphysema can be confidently assessed with CT methods. Finally, the
      simple visual score may be as reliable as such highly sophisticated new methods
      as the spiral expiratory density mask. Expiratory studies offer new insights into
      different normal and abnormal features of COPD and respiratory impairment.

PMID- 9244915
TI  - [Magnetic resonance angiography in the study of pulmonary veins: TOF 3D versus
      2D].
AB  - The aim of this work was to optimize the magnetic resonance angiography (MRA)
      technique for the selective study of the pulmonary veins. Twenty consecutive
      patients (13 men and 7 women; mean age: 30.5 years) were examined. MRA was
      performed with a 1 T superconductive magnet and the 3D time of flight (TOF)
      technique. Fast sequences (3D FISP: TR 58 ms, TE 6 ms, FA 20 degrees, matrix 192
      x 256; and 2D FLASH: TR 44 ms, TE 10 ms, FA 30 degrees, matrix 192 x 256) were
      used. Coronal and sagittal images were submitted to MIP processing; presaturation
      pulses for the pulmonary arteries were located in the mediastinal region. In the
      right lung, 3D TOF on the coronal plane well showed 124 veins, while sagittal
      images showed 106 veins. In the left lung, 3D TOF on the coronal plane well
      showed 96 vessels, while sagittal images showed 44 vessels. In the right lung, 2D
      TOF on the coronal plane well showed 54 veins, while sagittal images showed 36
      vessels. In the left lung, 2D TOF on the coronal plane well showed 22 vessels,
      while sagittal images showed 21 vessels. Therefore, 3D TOF yielded better results
      than 2D TOF (p < 0.05). To conclude, 3D TOF with contrast agent administration is
      a useful tool to study the pulmonary veins; those with a larger caliber are
      better depicted and the integration of coronal and sagittal images depicts more
      veins.

PMID- 9244916
TI  - [The crescent and the periluminal halo: two computer tomography signs of aortic
      aneurysm with risk of rupture?].
AB  - PURPOSE: To assess the prevalence, significance, and practical value of two
      recently described CT signs of instable aneurysm: the crescent sign (a
      curvilinear high-attenuating density within the thrombus) and the periluminal
      halo (a low-attenuating internal layer of the thrombus around the patent lumen).
      MATERIAL AND METHODS: Among the CT examination performed in the last 5 years, we
      retrospectively selected the nonruptured aneurysms with a diameter exceeding 4 cm
      (no. = 93, average diameter 5.1 cm, unenhanced images in 28 cases and enhanced in
      84) and the ruptured aneurysms (no. = 16, average diameter 6.7 cm, unenhanced
      images in 9 cases and enhanced in 9). We studied the prevalence of the crescent
      and halo sign, their relationship with the aneurysm diameter, and the effect of
      contrast enhancement. RESULTS: The crescent sign was identified with a
      statistically significant prevalence in ruptured (37.5% of cases) over
      asymptomatic aneurysms (5.5%); the halo, instead, had the same frequency in the 2
      groups (12.5% and 9.5%, respectively). Both signs were more frequent in bigger
      aneurysms and were recognizable without differences in unenhanced and enhanced
      images. CONCLUSIONS: The crescent sign, though not exclusive of aneurysmal
      rupture, indicates instability and its detection should lead to careful follow-up
      or surgical repair. The halo seems to have no real value as risk factor.

PMID- 9244917
TI  - [Diagnosis with defecography of puborectal muscle syndrome].
AB  - The puborectalis syndrome is a defecation disorder supported by the nonrelaxation
      of puborectalis sling with consequent dyschezia. We report on a series of 98
      patients submitted to clinical examination, defecography, anorectal manometry,
      electromyography and intestinal transit time studies. Puborectalis anatomy and
      physiology are briefly reviewed. The main symptoms of puborectalis syndrome in
      our patients were incomplete defecation (89%) and intermittent evacuation (63%);
      28% of patients turned to finger defecation. In all patients, defecography showed
      an abnormal increase in puborectalis impression on the posterior anorectal wall,
      reduced anorectal angle opening under straining (mean value: 113 degrees) and
      prolonged expulsion time with barium pooling in the ampulla (mean evacuation
      time: 38 seconds). Such anorectal abnormalities as rectal mucosal prolapse (47
      cases) and anterior rectocele (36 cases) were also associated. In 33 of 98
      patients (34% of cases), sling assessment by bidigital palpation at preliminary
      clinical examination revealed puborectalis hypertonia, which was later confirmed
      at defecography. Manometry was not specific for the diagnosis of puborectalis
      syndrome, detecting increased external anal sphincter pressure under straining in
      24 of 35 patients (68.8%). Puborectalis activity was increased under straining in
      16 subjects submitted to electromyography. Intestinal transit time studies showed
      a typical expulsion delay and radiopaque marker pooling in the ampulla in 18 of
      23 patients (78.2%). In our experience, defecography is a useful, simple and
      noninvasive method for the accurate diagnosis of the puborectalis syndrome.

PMID- 9244918
TI  - [Fetal biliary lithiasis: ultrasonographic diagnosis and clinical interpretation.
      Report of 3 cases].
AB  - Fetal cholelithiasis was first diagnosed in 1983 and since then there have been
      only few reports about the presence of gallstones in the fetus. Maternal
      conditions, fetal or obstetrical predisposing risk factors have been proposed to
      have a causative role, but the pathogenesis of fetal gallstones remains unknown.
      Clinical sequelae of fetal gallstones are poorly understood as well as the role
      of fetal cholelithiasis in predisposing the adult to gallstones. We report on 3
      patients whose cholelithiasis was diagnosed by obstetrical ultrasonography.
      Repeated ultrasound scans were performed in each patient until resolution of the
      US images. The goal of US was to correctly identify the number, size, and US
      features of the material within the gallbladder. The presence of distal shadowing
      or comet-tail artifact was assessed. Multiple, small echogenic foci without
      distal shadowing were recognized in the fetal gallbladder in our patients.
      Echogenic material was present at the US exams after birth in two patients and
      disappeared in the second month of life. In the third case echogenic foci
      disappeared during pregnancy. In all the cases, US showed no biliary tract
      abnormality, and neither the mothers nor the patients had clinical or laboratory
      findings consistent with liver or biliary diseases. The Authors discuss a
      diagnostic protocol to detect and follow-up gallstones in the perinatal period by
      ultrasonography. In our experience, fetal cholelithiasis confirmed to be a self
      limiting disease without complications and did not require any form of therapy.
      However, a close follow-up is indicated in these patients until spontaneous
      resolution is demonstrated by US.

PMID- 9244919
TI  - [Role of Doppler color ultrasonography and of flowmetric analysis in the
      diagnosis and follow-up of Grave's disease].
AB  - Hyperthyroidism in Graves' disease is caused by the presence of circulating
      autoantibodies to the THS receptors on the thyroid cells. Thyroid-suppression
      therapy prevents hormone production directly, without affecting the pathogenetic
      process. We performed color Doppler US of the thyroid gland and pulsed Doppler
      analysis of thyroid artery flow in 21 patients with Graves' disease before and
      during medical treatment. US results were compared with those of a control group
      of 40 healthy subjects and correlated with the values of thyroid hormones, TSH,
      and thyroid microsomal and thyroglobulin antibodies. The thyroid gland was
      hypovascularized in the control group. Pulsed Doppler examination of the thyroid
      arteries exhibited peak systolic velocity of PSV 20 +/- 4 cm/s, diastolic
      velocity of 8 +/- 1 cm/s, and resistive index of 0.60 +/- 0.04. The thyroid gland
      of Graves' disease patients was hypervascularized. Pulsed Doppler examination of
      the thyroid arteries exhibited peak systolic velocity (PSV = 51 +/- 12 cm/s), end
      diastolic velocity (VD = 15 +/- 4 cm/s), and resistive index (RI = 0.71 +/- 0.04)
      significantly higher than in normal subjects (p < 0.001). Circulating thyroid
      hormones and flow parameters normalized after 6-8 months of medical therapy (PSV
      = 20 +/- 6 cm/s, VD = 9 +/- 3 cm/s, RI = 0.58 +/- 0.07). Conversely, the color
      Doppler patterns normalized only in a patient with normal TSH and antibodies.
      Sampling of the thyroid arteries proved more repeatable than sampling of
      parenchymal vessels.

PMID- 9244920
TI  - [Antiblastic hypoxic stop-flow perfusion in the treatment of liver metastasis:
      preliminary results].
AB  - PATIENTS AND METHODS: 27 patients (14 men and 13 women aged 35 to 71 years;
      average: 59 years), with 3-11 months' follow-up (average: 5 months) were treated
      for hepatic metastases (17/22 from colorectal, 10/22 from other primary tumors)
      with hypoxic locoregional hepatic perfusion. Sixteen of 22 patients had been
      pretreated with resection, systemic chemotherapy or freeflow locoregional
      infusion. Our protocol consists in blocking arterial flow with an occlusion
      balloon catheter inflated in the hepatic artery; the main catheter channel is
      connected with a pump system and 250-300 ml saline with 30-40 mg Mitomycin C are
      perfused in the arterial hepatic system. Embolization with a gelatin sponge is
      performed after the end of perfusion. RESULTS: 19/27 patients are still alive,
      and 8/27 are dead but death was caused by the progression of intrahepatic disease
      in only 2/27 (7%). Iatrogenic lesions of the arterial wall were shown at follow
      up DSA in 15/22 patients (56%). Thirteen CR (48%) and 9 PR (33%) were
      demonstrated at CT follow-up, amounting to 81% of objective responses. Follow-up
      showed a clinical CR in 12/18 symptomatic patients (66%). No case of hematologic
      toxicity was observed. Mean CEA values changed from 129 to 10.60. Twelve of 27
      patients exhibited mild posttreatment sequels, none of them lasting longer than
      three days; ischemic cholecystitis was seen in 3/15 cases (14%). CONCLUSIONS: The
      occlusion catheters on the market are not optimal for this procedure; the
      axillary percutaneous approach is advantageous. CR rate was very high in our
      series but the objective response rate doses do not differ from those in the
      series with free-flow procedures. The highest CR rate was observed in untreated
      patients and in hypervascularized lesions; the rate of clinical sequels was low,
      clinical CR rates were high and there was no hematologic toxicity. This well
      tolerated procedure provides good local disease control, but the high rate of
      deaths from extrahepatic progression suggests that systemic chemotherapy and long
      step intraarterial perfusion be combined.

PMID- 9244922
TI  - [Percutaneous occlusion of small patent ductus arteriosus with detachable
      Gianturco spring coils. Preliminary results].
AB  - INTRODUCTION: Botallo's duct occlusion with Gianturco coils is effective in the
      fistulas with max. diameter of 3.3 mm. The insertion technique does not permit to
      control coil positioning inside the fistula and the coil itself may migrate to
      the pulmonary artery. We report our experience with a new system of temporary
      hookup of the coil proximal end to a metal thread (Cook device) which permits to
      change the position of the coil or to replace it. MATERIALS AND METHODS: We
      treated 6 patients with persistence of Botallo's duct (O: 2-3.5 mm, mean: 2.9
      mm). The duct was occluded in 5/6 patients. The coil migrated to the pulmonary
      artery in a case where the hookup system permitted to retrieve and then replace
      it with a bigger coil which was also retrieved because it was too big for the
      small aorta. No complications were observed. RESULTS: Follow-up chest films at 24
      hours showed coil stability and color Doppler US confirmed the occlusion. The
      patients were discharged after 24 hours. The follow-up at 6 months confirmed the
      procedure success. CONCLUSIONS: The hookup system was effective to control coil
      positioning and to extract and replace the coils. The effectiveness of this
      occlusion technique would be improved if a wider range of coil sizes and types
      were available.

PMID- 9244921
TI  - [Treatment of intrahepatic arteriovenous fistula after biopsy. Results in 5
      chemoembolization candidates with hepatocarcinoma].
AB  - We report our experience in the treatment of post-bioptic intrahepatic
      arterioportal fistulas (HAPF) in 5 patients with hepatocellular carcinoma (HCC)
      treated February, 1993, to May, 1995. In this retrospective study, we reviewed
      the imaging findings and clinical records of 3 men and 2 women (age range: 49-71
      years) with HCC previously diagnosed with US, CT and biopsy. HAPF was detected by
      angiography (DSA) performed before chemoembolization (TACE). All HAPFs were
      referrable to biopsy (14-gauge Thru-Cut needle) and were treated with platinum
      coils positioned through coaxial catheters. TACE was performed immediately after
      or within a week of HAPF embolization. Therapeutic response after TACE was
      assessed on the basis of clinical and CT findings, while HAPF embolization
      success was assessed on the basis of DSA and color Doppler US findings.
      Reembolization was required in two patients--7 maneuvers in all in 5 patients.
      Complete HAPF occlusion was demonstrated in 4 patients during color Doppler
      follow-up and immediately after and at 13 and 24 months (in 2 patients) at DSA.
      Two of 5 patients died, one because of liver failure after 15 months' follow-up
      and the other because of complications related to liver transplantation at 11
      months' follow-up. Of the extant 3 patients, one underwent liver transplantation
      and was followed-up for 25 months, while the other two are alive after 24 and 13
      months, respectively. Our experience demonstrates that HAPF embolization in HCC
      patients is really useful for hemodynamic redistribution before TACE and to avoid
      further HAPF progression.

PMID- 9244923
TI  - [Extranodal lymphomas: computerized tomography features and differential
      diagnosis].

PMID- 9244924
TI  - [Neoadjuvant combined hormonal therapy and radiotherapy with external beam
      irradiation in prostatic carcinoma].
AB  - From January, 1991, to December, 1995, forty-two patients with prostatic cancer
      (T2-T4: 40 patients) were treated with a luteinizing hormone-releasing hormone
      (LHRH) analog (2 administrations before and 3 during irradiation), Flutamide (1
      month) and external beam radiation therapy (45 Gy to the whole pelvis and a 20 Gy
      boost). All patients completed the protocol and the LHRH analog was continued for
      1-6 months in 5 patients with partial response at the end of radiotherapy. The
      incidence of acute toxicity was low according to the Radiation Therapy Oncology
      Group and European Organization for Research and Treatment in Cancer score
      (grades 1-2; 19% hematologic, 36% intestinal and 38% urological toxicity). At a
      median follow-up of 21 months (range: 1-60 months), one patient had local disease
      progression and lung metastases and two had bone metastases; the three relapsing
      patients were given the LHRH analog and exhibited partial response to rectal
      examination (1 case) and to bone scan (2 cases). Pain disappeared completely in
      both the patients with bone metastases. Overall 3-year survival and disease-free
      survival rates were 97% and 79%, respectively. Disease-free survival was
      significantly related to cT (at 3 years: cT2: 100%; cT3: 81.2%; log rank test:
      0.0081). Late toxicity was observed in two patients: rectal bleeding in one case
      and chronic diarrhea in the other. The combined protocol used in this study was
      feasible and well tolerated. Our results seem to confirm the promising
      preliminary results of Radiation Therapy Oncology Group 8610 study.

PMID- 9244925
TI  - [The anal canal: 2 cycles of radiochemotherapy and boost brachytherapy].
AB  - From 1988 to 1996, twenty-six patients with epidermoid anal cancer were examined
      at the Radiotherapy Department of Universita Cattolica del S. Cuore, Rome. At
      diagnosis, 13 patients were stage II, 11 patients were stage III, 2 patients had
      a small recurrence after local excision. All the patients were treated with
      concomitant radiochemotherapy followed by a brachytherapy boost. Treatment was
      carried out in two cycles 4-5 weeks apart. Chemotherapy consisted of 5FU (1,000
      mg/sqm, continuous infusion over the first 4 days) and Mitomycin C (10 mg/sqm on
      day 1, bolus administration). Radiotherapy was administered with two AP opposed
      coaxial beams of the same size. The target was T and inguinal, external, internal
      and common iliac lymph nodes. The total dose for each cycle was 23.4 Gy,
      administered with conventional fractionation and a daily dose of 180 cGy. Four
      six weeks after the end of cycle 2, the patients received a boost of interstitial
      brachytherapy. During concomitant radiochemotherapy, grade 3-4 (RTOG-EORTC scale)
      acute hematologic and cutaneous toxicities were observed in 15% and 4% of
      patients, respectively; treatment was discontinued in 4 patients. Complete
      response was observed in 21 patients (81%) and partial response in 5 (19%). The
      later underwent surgery, namely local excision in 1 patient and abdominoperineal
      resection in 4 patients. The median observation period of our study population
      was 45 months. Five-year actuarial local control of the 26 patients was 88%. Five
      year actuarial survival was 75% and sphincter conservation 77%. Our results
      confirm the data reported by Cummings of Princess Margaret Hospital, who observed
      low toxicity when the two cycles of concomitant radiochemotherapy are split.
      Randomized phase-III studies should clarify the potential role of the new
      radiochemotherapy combinations which should be compared with reference treatments
      providing repeatable results and low toxicity. Our treatment may make a reference
      for more innovative combinations of radiochemotherapy.

PMID- 9244926
TI  - [Embryonal rhabdomyosarcoma in adults: a case report].

PMID- 9244927
TI  - [Migrant spondylitis. Report of 2 cases: magnetic resonance features].

PMID- 9244928
TI  - [A case of triphalangeal thumb in a newborn].

PMID- 9244929
TI  - [A case of male breast metastasis from adenocarcinoma of the colon].

PMID- 9244930
TI  - [Computerized tomography features of the accessory cardiac bronchus. A case
      report].

PMID- 9244931
TI  - [Doppler color, computerized tomography, and magnetic resonance of a case of
      congenital arteriovenous malformation of the pelvic branches of the hypogastric
      artery].

PMID- 9244932
TI  - [Omental seeding of hepatocarcinoma: report of a case].

PMID- 9244934
TI  - [A case of non-endemic Burkitt's lymphoma of the colon].

PMID- 9244933
TI  - [Right ureteral stenosis in cephalic pancreatitis. A case report].

PMID- 9244935
TI  - [Renal changes in a case of type 2 mixed cryoglobulinemia in a patient with B
      cell lymphoma. Computerized tomography, ultrasonography, and radioisotopic
      findings].

PMID- 9244936
TI  - [Percutaneous embolization with tungsten coils of a splenic artery aneurysm:
      report of a case].

PMID- 9244937
TI  - [Evaluation of the sensitivity of the Woo test for the detection of Trypanosoma
      vivax].
AB  - The haematocrit centrifuge technique (HCT), or Woo test, is the technique most
      commonly used for diagnosis of animal trypanosomosis, but its sensitivity is not
      well defined. Depending on the authors, the sensitivity of the Murray technique
      (dark' ground buffy coat method, or DG/BCM) is higher, equal or lower than that
      of the Woo test for the detection of Trypanosoma vivax. Most authors have
      compared particular techniques relatively to other techniques, rather than
      attempting to measure the sensitivity of the tests in relation to a fixed
      reference. The relative sensitivity of particular tests appears to vary between
      technicians. The aim of the present study was to measure the sensitivity of the
      Woo test for French Guiana T. vivax detection, using blood samples with pre
      determined levels of parasitaemia, ranging from 1 to 1767 parasites/ml, that were
      prepared by mixing infected ovine blood with non infected ovine blood. A simple
      technique is described for the enumeration of parasites in blood. The mean
      positivity level of the Woo test in sheep was about 200 +/- 110 T. vivax/ml. The
      sensitivity of the test was 100% above 700 parasites/ml, about 80% between 300
      and 700, 50% between 60 and 300, and was negligible below 60 parasites/ml.
      Parameters are provided to estimate parasitaemia based on the number of parasites
      observed between slide and cover slip (parasitaemia > 2000) or in the capillary
      tube (parasitaemia < 2000). Sensitivity of the techniques for detection of active
      infection could be evaluated in comparison with fixed values such as known
      parasitaemiae, artificially created, as described here.

PMID- 9244938
TI  - [Epidural analgesia in labor. An area of continuous progress].

PMID- 9244939
TI  - [Analgesic effectiveness and repercussions on the progress of labor of small
      doses of bupivacaine and fentanyl in continuous peridural perfusion].
AB  - OBJECTIVES: To compare the analgesic efficacy and repercussion on labor of early
      administration of two different concentrations of bupivacaine/fentanyl in
      continuous epidural perfusion, in comparison with a control group receiving no
      epidural anesthesia. PATIENTS AND METHODS: One hundred fifty patients were
      distributed among 3 groups. Group I (n = 50) received no epidural analgesia.
      Group II (n = 50) and III (n = 50) received test doses of 3 ml of bupivacaine
      plus adrenalin 1/200,000. After 5 minutes each patient in the study groups
      received 13 ml of the solution assigned (group II: 0.04% bupivacaine plus
      adrenalin 1/2,500,000 and fentanyl 2.5 micrograms/ml; group III: 0.0625%
      bupivacaine plus adrenalin 1/1,600,000 and fentanyl 2 micrograms/ml). Five
      minutes later a perfusion of 12 ml/h-1 of the same solution was delivered until
      dilation was complete. RESULTS: Epidural perfusion was started at 2.5 +/- 0.93 cm
      of dilation (group II) and 2.3 +/- 0.92 cm (group III). There were no
      statistically significant differences in either duration of labor until full
      dilation or expulsion among the groups. Pain assessed on a visual analog scale
      evolved from a baseline mean of 4.5 to 5 in the three groups, reaching 8.9 +/-
      0.74 (group I), 0.24 +/- 0.89 (group II) and 0.28 +/- 0.57 (group III). There
      were no significant differences in fetal presentation or Apgar scores among the
      three groups at the end of delivery. CONCLUSION: Both solutions provide good
      analgesia during labor with minimum undesirable side effects. Low epidural doses
      of bupivacaine and fentanyl started early do not affect the course of labor.

PMID- 9244940
TI  - [The effects of carbonation on 2% mepivacaine in epidural anesthesia].
AB  - OBJECTIVES: To evaluate the clinical effects of 2% carbonated mepivacaine in
      arthroscopic surgery of the knee. PATIENTS AND METHOD: Thirty patients were
      enrolled in this prospective, double-blind study, and randomly assigned to two
      groups to receive 2% mepivacaine plus saline (group I, n = 15) or 2% mepivacaine
      plus bicarbonate soda. The alkalinized solution was prepared by adding 0.1 mEq of
      8.4% bicarbonate soda to each ml of 2% mepivacaine. A total volume of 16 ml of
      the mixture assigned was injected through an epidural catheter. Variables
      recorded were time until sensory blockade, maximum cephalad spread, number of
      marked dermatomes, regression time, degree of motor blockade and time until start
      of surgery. RESULTS: Fewer marked dermatomes were observed in group II than in
      group I after 5 minutes (6.5 +/- 3.3 versus 9.3 +/- 2.8), after 15 minutes (1.5
      +/- 1 versus 3 +/- 2.2), at 20 minutes (1 +/- 1.1 versus 1.8 +/- 0.9) and after
      25 minutes (0.4 +/- 0.7 versus 1.2 +/- 1.2) (p < 0.05). We observed no
      significant differences in time until start of analgesia, maximum cephalad spread
      of sensory blockade or degree of sensory blockade. CONCLUSIONS: Alkalinization of
      2% mepivacaine delivered epidurally improves the quality of blockade, decreasing
      time until start of surgery. However, the slight clinical significance of these
      results does not appear to justify general application.

PMID- 9244941
TI  - [The use of propofol in carotid surgery].
AB  - OBJECTIVE: To compare two anesthetic techniques in carotid surgery. The first
      technique was propofol in continuous perfusion throughout the procedure (group A)
      and the other used etomidate for anesthetic induction and isoflurane for
      maintenance (group B). PATIENTS AND METHODS: The patients were assigned randomly
      either to group A (n = 23) to receive propofol in continuous perfusion for
      induction (0.8-1 mg/kg) and for maintenance (4-6 mg/kg/h) or to group B (n = 25)
      to receive etomidate (0.25 mg/kg) for induction and isoflurane 0.6-0.8% for
      maintenance. Ventilation was maintained with O2/N2O. Systolic and diastolic
      arterial pressures (SAP and DAP) and heart rate were measured at baseline, during
      induction (minutes 1, 2, 3, 5 and 10), immediately before and 1 minute after
      interruption of carotid flow, once flow had been released and after extubation.
      Other variables recorded were time until awakening and extubation, presence of
      pain, degree of well-being, need for analgesics and vasodilators, perioperative
      complications and time until hospital release. RESULTS: The variations in
      hemodynamic parameters during induction and during maintenance were similar for
      both techniques. Orotracheal intubation increased SAP in both groups. Time until
      eye opening and awakening were shorter in group A but the difference was not
      statistically significant. CONCLUSIONS: The use of propofol for induction and
      maintenance during carotid surgery was as safe as conventional anesthetic
      technique with etomidate and isoflurane.

PMID- 9244943
TI  - [Oxygen consumption during anaphylactic shock].
AB  - We report the case of a 49-year-old man who suffered anaphylactic/anaphylactoid
      shock within the first few minutes of reaching the recovery room after
      unremarkable coronary surgery and revascularization. Adequate monitoring
      permitted differential diagnosis and establishment of specific treatment
      Monitoring also allowed us to document hemodynamic changes and oxygen consumption
      during this instance of anaphylactic/anaphylactoid shock.
      Anaphylactic/anaphylactoid shock caused significant vasoparalysis with decreases
      in arterial pressures, reduction of oxygen consumption and discrete changes in
      oxygen exchange. The reposition of volume and administration of adrenaline were
      insufficient. Appropriate management of noradrenaline perfusion, which was made
      possible by complete monitoring, was essential for reestablishing normal
      hemodynamic and oximetric readings and preventing myocardial ischemia.

PMID- 9244942
TI  - [Endogenous opioid peptides and the immune system].
AB  - Several studies have demonstrated that endogenous opioid peptides produced by the
      neuroendocrine system can modulate several immunological functions. Immune system
      cells have also been shown to have the ability to synthesize and release such
      peptides. This would mean that the neuroendocrine and immunological systems share
      molecules and opioid receptors and it may be that peptides produced by the
      neuroendocrine system modify immunocompetence and that these same substances
      released by macrophages that infiltrate inflamed tissue also act on the pain
      response in the zone of lesions. We aimed to investigate the immunoregulatory
      function of endogenous opioid peptides and their effects on the complement
      system's natural "killer" cell activity, chemotaxis, phagocytosis and oat cell
      activity.

PMID- 9244944
TI  - [Macroglossia after surgery of the posterior fossa].
AB  - We report a case of upper airway obstruction as a result of delayed macroglossia
      in a 17-year-old patient following posterior cranial fossa surgery performed with
      the patient in a sitting position. Airway obstruction is a life-threatening
      complication and must be treated promptly. Diverse etiological mechanisms are
      discussed, along with preventive and therapeutic measures.

PMID- 9244945
TI  - [Subconjunctival anesthesia: an alternative for vitrectomy in mitochondrial
      myopathy].
AB  - The case of a 63-year-old woman with mitochondrial myopathy with palpebral ptosis
      and nighttime nasal home oxygen therapy is reported. The patient successfully
      underwent outpatient vitrectomy with subconjunctival anesthesia, receiving no
      premedication or sedation during the operation. Subconjunctival analgesia was
      provided, with prior instillation of an anesthetic collyrium followed by
      subconjunctival injection of 1 ml of 0.4% bupivacaine and 2% lidocaine. Analgesia
      during surgery was satisfactory. We review the possibilities of using this
      technique in patients at high risk of presenting postoperative complications
      after general anesthesia, and discuss the possible side effects on musculature
      when peribulbar or retrobulbar anesthesia is provided.

PMID- 9244946
TI  - [Pneumothorax during anesthesia complicating needle aspiration of
      microcalcifications in the breast. Presentation of a case].

PMID- 9244947
TI  - [Intracranial hypotension and epidural drainage with aspiration].

PMID- 9244948
TI  - [The post-reperfusion syndrome in liver transplantation].

PMID- 9244949
TI  - [Epidural abscess: a complication of the use of corticoids in the treatment for
      back pain].

PMID- 9244950
TI  - [Cesarean and prolapse of the mitral valve].

PMID- 9244951
TI  - [A comment concerning high-frequency jet ventilation in laryngeal microsurgery].

PMID- 9244952
TI  - [Protocol for management of an unexpected unsuccessful intubation].

PMID- 9244953
TI  - [Trefoil peptides in the protection of the gastrointestinal mucosa].

PMID- 9244954
TI  - [The epidemiology of the gastroduodenal damage induced by aspirin and other
      nonsteroidal anti-inflammatory drugs].
AB  - A substantial body of studies (controlled, cohort and case-control studies) now
      confirm the long established impression that there is an increased prevalence of
      gastric and duodenal ulcer and of associated complications in subjects treated
      with aspirin (ASA) or with non-steroidal anti-inflammatory drugs (NSAIDs). The
      overall percentage of ulcers/erosions in patients treated with ASA ranges from 10
      to 50% with a relative risk of bleeding ranging from 1.8 to 15%. The overall
      relative risk of ulcers/erosions in NSAIDs-treated subjects is around 3%, with
      complications detectable in 2.4% of cases. The risk of lesions and complications
      associated with ASA/NSAIDs is more marked in patients aged over 65, in those with
      a previous history of ulcer (both symptomatic and silent), in those treated with
      substantial doses or with combinations of NSAIDs and in those concomitantly using
      anticoagulants and/or steroids. The epidemiological data highlight the importance
      of implementing ASA/NSAIDs therapy only when strictly necessary as well as the
      advisability of adopting as broad a range of measures as possible to reduce the
      tissue-damaging effects of these pharmacological agents.

PMID- 9244955
TI  - [Who are the "non-dippers": an insight from the ambulatory monitoring of arterial
      pressure in heart transplant patients].
AB  - This study was performed in order to define who are the "non-dippers", knowing
      that their present definition does not imply any explanation about the
      mechanisms. The investigation was performed on 34 heart transplanted patients, 28
      males (mean age 52 +/- 11 years) and 6 women (mean age 35 +/- 14 years), knowing
      that the "non-dippers" were described as the hypertensives who are devoid of the
      expected nocturnal fall in blood pressure (BP). The "non-dipping" phenomenon was
      investigated by exploring the BP 24-h pattern via ambulatory non-invasive BP
      monitoring, and by applying the rhythmometric analysis for quantifying the BP
      circadian rhythm. The study provided evidence that the "non-dippers" can be found
      among the hypertensives as well as the normotensives, suggesting that high BP is
      not a necessary condition for the "non-dipping" phenomenon, and vice versa. Both
      the normotensive and hypertensive "non-dippers" were seen to show stereotypic
      changes in BP circadian rhythm. There are normotensive and hypertensive "non
      dippers" with or without the BP circadian rhythm. The "rhythmic non-dippers" show
      a BP circadian rhythm which is inverted in phase or demodulated in amplitude. The
      "non-dippers" are, thus, a heterogeneous category.

PMID- 9244956
TI  - [Alendronate-induced esophagitis. A report of 2 cases].
AB  - Two cases of esophagitis associated with the use of alendronate are described.
      Both patients were women with no past history of heartburn or dyspepsia, who
      started alendronate for postmenopausal osteoporosis at least one week before the
      symptoms onset, by taking the drug with half a glass of tap water at bedtime. The
      first patient suffered from a severe chest pain; endoscopy showed confluent
      erosions of the lower third of the esophagus. The second patient had odynophagia
      and developed exudates and greyish plaques on the mucosa of the upper third of
      the esophagus. Histological examination of the esophageal specimens of both
      patients disclosed no Monilia, hyphae, or nuclear viral inclusions. Both patients
      stopped alendronate with complete recovery at follow-up. A brief review of the
      etiopathogenesis of pill esophagitis is also presented. Finally, emphasis is
      placed on the selection of patients for therapy with alendronate with warnings on
      how to take the drug correctly.

PMID- 9244957
TI  - [Sepsis due to Pasteurella multocida in an HIV-positive patient].

PMID- 9244958
TI  - [Is active autonomous duodenitis a precursor of duodenal ulcer?].
AB  - Up to today, the relationship between autonomous nonspecific duodenitis (ANSD)
      has not yet been defined. ANSD has been noticed in about 26% of dyspeptic
      population. With reference to the presence of active inflammation, ANSD has been
      divided into chronic duodenitis (CD) (77.7%) and in active duodenitis (AD)
      (22.3%). The two duodenitis groups have been compared with a group of patients
      with duodenal ulcer (DU) in relation with the presence of duodenal gastric
      metaplasia (GM), of duodenal Helicobacter pylori (Hp) infection, of antral
      chronic gastritis (AG), of antral Hp infection, and in relation with the gastric
      secretion behaviour. The data concerning AD are superimposable to those of DU
      with presence of high percentage of duodenal GM, of duodenal Hp infection and of
      Hp positive AG. Furthermore, they present a gastric secretory profile similar to
      DU with prevalence of hyperchlorhydria and hyperpepsia. CD without activity, on
      the contrary, present values superimposable to dyspeptic population without
      duodenitis and DU. It is, therefore, that Hp positive AD can be considered as a
      possible precursor of DU. In periulcerous site, in fact, AD is present in more
      than 90% of cases.

PMID- 9244959
TI  - [The modes of transmission of Helicobacter pylori infection].
AB  - Helicobacter pylori plays an essential role in the development of several both
      acid-related and neoplastic gastroduodenal pathologies. There are still
      uncertainties about the transmission routes and the sources of H. pylori
      infection. Man is the only well established "reservoir" of H. pylori, while the
      role of other mammalians (cat, pig, primates), as sources of infection, is still
      controversy. Literature data suggest four different modalities of transmission of
      the infection: faeco-oral, oro-oral, gastro-oral, gastro-gastric. By faeco-oral
      route, the bacterium, excreted with faeces, might colonize water sources,
      becoming so available to be transmitted to man and other mammalians. By oro-oral
      route, H. pylori, which colonizes dental plaque and saliva, may be transmitted by
      saliva to other individuals. The gastro-oral route is the typical modality of
      transmission in the childhood, when H. pylori uses the mucous achlorhydric
      vomitus of the children to infect a new host. Finally, by gastro-gastric route
      the bacterium might be transmitted by endoscopic procedures. In conclusion, we
      believe the different modalities of transmission may be contemporaneously
      involved, since none per se is able to explain the widespread occurrence of H.
      pylori infection.

PMID- 9244960
TI  - [Magnetic resonance angiography: a future endeavor in clinical methods].

PMID- 9244961
TI  - [Restless legs syndrome--current aspects].
AB  - Although the Restless-Legs-Syndrome (RLS) is harmless, it can be considerably
      bothersome on occasions. It seems to affect 1-5% of the population. The minimal
      criteria for diagnosis are: Symmetric or asymmetric dysesthesias of the lower,
      sometimes also of the upper extremities, present at rest, especially at night.
      This induces a need to move. Moving gives always relief, but only for a few
      seconds. Occasionally, dysesthesia can be painful. Additional features are:
      Involuntary, rhythmic retraction movements occurring especially at night, during
      sleep stages I und II. Sleep is disrupted and superficial, followed by daytime
      fatigue. Aetiologically, it is a mostly primary or hereditary disease, but may go
      along with uremia, diabetes and rheumatoid arthritis. Pathophysiologically there
      seems to be a malfunction of dopamine and opiate receptors in the central nervous
      system. Recently, morphological modifications have been found in peripheral
      nerves. Coffeine has been claimed as causative factor, but its role remains
      questionable. Therapy shows a high success rate. Some patients may complain about
      some remaining symptoms even with high doses of medication. Although
      carbamazepine, clonazepam and clonidine showed satisfactory results in controlled
      studies, dopaminergic agents and opiates have many advantages. In contrast to the
      former compounds, the latter are also effective against periodic movements in
      sleep. Side effects will be discussed according to the literature. In the second
      part of this paper, practical aspects concerning the care of RLS patients are
      considered.

PMID- 9244962
TI  - [When and why are antibiotics indicated in airway infections (except
      pneumonia)?].
AB  - Infections of the upper airways reduce life quality of adults on average twice,
      that of children even 4 to 8 times a year. Usually these are viral infections
      subsiding spontaneously without antibiotics. Only if concomittant circumstances
      arise and in specific clinical situations (otitis, sinusitis, tonsillitis,
      epiglottitis) as well as in acute exacerbation of chronic bronchitis are
      antibiotics already indicated at first consultation. The physician who is usually
      consulted by a patient with increasing discomfort under self-medication and who
      is expecting an antibiotic treatment has next to the clinical findings and prior
      laboratory test results to consider before all the individual (home, workplace,
      school) and epidemiologic (influenza) situation, the possible pathogens, their
      susceptibility to antibiotics as well as the side effects and costs for the
      decision to prescribe antibiotics. Today because of an increasing pressure of
      selection for pathogens resistant to antibiotics a greater reluctance to
      prescribe antibiotics is recommended. This requires close follow-up of the
      patient with symptomatic treatment or only short "probatory" antibiotic therapy
      and a good patient-physician relationship.

PMID- 9244963
TI  - [Importance of AFPplus-screening in daily practice. Evaluation of 2641 analyses].
AB  - Since 1991 the measurement of 3 biochemical parameters for the risk assessment of
      trisomy 21 pregnancy (AFPplus, Alpha-check) is also offered by private
      laboratories in Switzerland. This work aimed at the proof of reliability of this
      risk analysis in the hands of practitioners and private laboratories. The
      investigated cohort included 2,641 pregnant women. An anonymous questionnaire on
      the outcome of pregnancy furnished informations in 97% of cases (2,561 cases). At
      a trisomy 21 risk cutoff of one to 380, 9% of the pregnant women had conspicuous
      AFPplus results (trisomy 21-risk > 1 to 380; age distribution at term: 17 to 45
      years; median 29.4 years). Among the conspicuous cases were 8 with trisomy 21, 1
      with trisomy 18, 5 spontaneous abortions and 3 special cases. Seven of a total of
      9 trisomies were detected by the screening. From these data the following
      diagnostic parameters for AFPplus have been calculated: specificity 91.0%,
      sensitivity 77.8%, positive predictive value 99.9%, false positive rate 9.0%,
      false negative rate 22.2%. The use of AFPplus by a practitioner cooperating with
      a private laboratory thus reveals a detection rate comparable to that known from
      larger centers. AFPplus by a practitioner cooperating with a private laboratory
      thus reveals a detection rate comparable to that known from larger centers.
      AFPplus allows to individualize the statistical age-related risk of a pregnant
      women before age 35. Above age 35 AFPplus may support the indication for cases
      suitable for cytogenetic investigation. Thorough personal information of the
      patient before the 16th pregnancy week by the practitioner or by genetic
      counseling has without any doubt first priority.

PMID- 9244964
TI  - [Neytumorin as biomodular onco-therapy--allegations without documentation].
AB  - NeyTumorin is a combination of peptides and proteins of 15 different organs from
      fetal and young pigs and cows. The list of indications ranges from cancer
      prevention to long-term treatment of malignancies. One vial of NeyTumorin-Sol
      costs DM 122.34. The therapy for a patient with a T1-2N0M0 cancer costs about DM
      16,500 and an advanced stage up to over DM 100,000. The inventor of the
      Cytoplasmatic Therapy is K.E. Theurer. About 40 years ago, he founded the
      Vitorgan-Pharmaceutical Company which produces and distributes NeyTumorin. It is
      claimed that "physiological repair aids" from the cytoplasm of healthy animal
      organs induce a "hygiogenization" of the disturbed metabolism and NeyTumorin has
      immunogenic and immuno-modulatory effects which are important for the efficacy.
      The promotors classify NeyTumorin as a biological response modifier. The
      components of NeyTumorin are not defined. Preclinical investigations showing
      direct cytostatic and immunomodulatory effects are not sufficiently documented.
      Often extremely high concentrations of NeyTumorin were used. Clinical studies
      including prospective randomized trials are not conclusive because of false or
      insufficient documentation. There is no proof for either the claimed mechanism of
      action nor for a clinical efficacy.

PMID- 9244965
TI  - [Chest pain and fever].
AB  - A 26 year old women was seen at our outpatient clinic because of fever, dyspnea,
      chest pain and night sweats. An echocardiography revealed a moderate pericardial
      effusion. Therapy with a nonsteroidal anti-inflammatory drug was started, but the
      patient did not improve clinically. A new left pleural effusion became manifest.
      Usual laboratory tests, serological tests and examination of pleural effusion
      were not conclusive. However, a tuberculin skin test was positive. The etiologic
      diagnosis of this pericarditis and pleuritis was obtained by thoracoscopic
      pleural biopsy, which yielded Mycobacterium tuberculosis.

PMID- 9244966
TI  - [Kidney colic under Indinavir [correction of indiavir] therapy in HIV infection].

PMID- 9244967
TI  - [Migration and its consequences for Switzerland--a postgraduate course of the
      Berne University].

PMID- 9244968
TI  - [Migration and health].

PMID- 9244969
TI  - [Border health examination].
AB  - The Swiss federal law on epidemics of 1970 requires that the federal government
      takes measures to prevent the importation of communicable diseases from abroad.
      Today, the only examination required is screening for tuberculosis with the aim
      of early detection and treatment. The examination is compulsory for asylum
      seekers and refugees as well as for migrant workers from countries other than the
      members of the EU and EFTA, the U.S.A., Canada, Australia, and New Zealand. In
      addition, routine vaccinations are offered to asylum seekers and refugees. The
      first measures for asylum seekers are taken at the border by the Swiss Red Cross
      on behalf of the Swiss Federal Office of Public Health. The follow-up is carried
      out in the cantons by medical institutions designated by the cantonal health
      authorities.

PMID- 9244970
TI  - [The role of the Swiss Medical Association (FMH) in health care of migrants].
AB  - The structure and function of the Swiss Medical Association (FMH) are summarized
      and important aspects of the medical care for the migrant population are
      presented. The relationship between the FMH and the Federal Office for Refugees
      (BFF) is highlighted. The FMH aims to facilitate the introduction of a
      confidential medical officer service which can be approached in particular
      circumstances. This function should be integrated in the asylum law.

PMID- 9244972
TI  - [Foreign patients in family practice: unsolvable problems for physician and
      patient?].

PMID- 9244971
TI  - [Asylum seekers and refugees in ambulatory health care: communication between
      physician and patient].
AB  - Communication between asylum seekers/refugees and general
      practitioners/physicians of the three main outpatient sectors for the Swiss
      national Health System (general practice, medical outpatient and accident &
      emergency departments) are being described and analysed. The data have been
      collected during three cross-sectional studies investigating the health status of
      asylum seekers and refugees and the health services provided to them. These
      studies addressed the problem exclusively from the point of view of the health
      care providers. Data on language capabilities, sociocultural aspects of
      communication and the necessity and availability of interpreters have been
      collected with questionnaires. The main results of the questionnaires have been
      followed up in group discussions with general practitioners. The majority of
      general practitioners/physicians felt that most of the communication problems
      were related to speaking a common language. Only about one out of two adult
      asylum seekers/refugees knew German, French, Italian or English. Particularly
      during the group discussions it was brought forward that cultural and social
      factors additionally complicate communication during patient-doctor interactions.
      When the data of the outpatient consultations of the main studies were analysed,
      it became obvious that interpreters were significantly more often present in
      consultations with patients with psychological/psychosocial diagnoses than those
      with somatic diagnoses (72% vs. 55%). This can be interpreted in two ways: (1) if
      a patient suffers from a psychological/psychosocial problem, it is more likely
      that an interpreter will be asked to assist during the consultation or (2) if an
      interpreter is present during a consultation, it is more likely that a
      psychological/psychosocial problem will be detected. With the exception of
      children, most of the general practitioners/physicians felt that non-professional
      interpreters (relatives, friends) were adequate for coping with most of the
      tasks. The following areas for improvements were identified: (1) availability of
      professional interpreters and quality as well as organisational issues related to
      interpretation, (2) language training for asylum seekers and refugees and (3)
      creation of awareness among general practitioners/physicians towards cultural and
      socioeconomic determinants of patient-doctor interactions and training.

PMID- 9244973
TI  - [What is your diagnosis? Calcified Echinococcus cysts in the spleen].

PMID- 9244974
TI  - [Physician-patient interaction from the migrant's viewpoint: suggestions for
      medical practice].
AB  - The quality of communication between physicians and migrants with psychosocial
      problems is critical to success of therapy and satisfaction with its course.
      Recommendations stress the importance of a patient-centered approach including a
      careful and migration-specific history-taking and of cooperation with colleagues
      and non-medical professionals, including migrants. These issues should be
      included in the medical training and in interventions made at the political
      level.

PMID- 9244975
TI  - [Turkish immigrants in ambulatory psychiatric treatment].
AB  - Socio-demographic and migration-specific particularities of first generation
      immigrants from Turkey (n = 133) treated at the Psychiatric Outpatient Department
      of the University Hospital, Basel were examined. 65.4% of the immigrants were
      men, 34.6% women. Women were significantly more often (p = 0.01) analphabetic
      than men and more often admitted as emergencies (p = 0.002). 66.7% of the married
      women and 57.8% of the married men were separated from their partners for more
      than one year because of migration. Adjustment disorder was the most frequent
      diagnosis in both genders. Opiate-dependency was not found in both genders, and
      none of the women were alcohol-dependent. The data are discussed on the
      background of socio-demographic characteristics of the Turkish immigrant
      population living in Basel and compared to studies made in Turkey.

PMID- 9244976
TI  - [The treatment of torture and war victims].
AB  - Torture is a means of repression in non democratic societies. Although banned, it
      is widely practised. About 30% of the refugees recognized 1987 in Switzerland
      were tortured. Torture and war lead to severe bio-psycho-social sequels which are
      described as "post traumatic stress disorder" (PTSD). This can be treated.
      Several centres for treatment of torture victims were recently established in
      many countries since health workers and health care providers felt helpless
      facing the consequences of torture and asked for professional support. The
      foundation of the Swiss Red Cross Therapy Centre for victims of torture was the
      response to their demand in Switzerland. The centre offers a wide range of
      therapies for victims of torture and training for health personnel. It further
      aims to facilitate the establishment of more institutions of this kind.

PMID- 9244977
TI  - [Health promotion and prevention in foreign populations in Switzerland:step-by
      step progress].
AB  - The national office for public health (Bundesamt fur Gesundheitswesen) aims to
      integrate the specific features of its target groups into its health promotion
      and prevention activities. This same strategy was applied to target the immigrant
      population. Initially these activities exclusively addressed prevention of Aids
      in immigrants from Spain, Portugal and Turkey. After 1993 they were extended to a
      wider range of issues and target groups. Women's health was one of the main
      topics which were added and activities were extended to groups from Africa, Latin
      America and to asylum seekers. Since 1995 drug and alcohol addiction became
      additional targets. In the course of these new activities groups from Italy and
      former Yugoslavia have also been addressed with respect to the various health
      promotion and prevention programmes. The cornerstones of the programme are (1)
      collaboration with the countries of origin of the various immigrant groups, (2)
      involvement of the target groups into the various activities and (3) the creation
      of awareness within Swiss institutions, organisations and immigrant
      administration offices towards specific problems of immigrants and their
      involvement into the various activities. A wide range of strategies have been
      employed which have already been evaluated. Amongst others those are training of
      health workers, who are themselves members of the various target groups,
      information events in immigrant clubs, telephone counselling in various
      languages. The results of the evaluation, problems and prospects for the future
      will be presented.

PMID- 9244978
TI  - [Oral ulcers in HIV infection].

PMID- 9244980
TI  - 11th Highlights of Gastroenterology in The Netherlands. Proceedings of a
      symposium. Venice, Italy, 28-31 March 1996.

PMID- 9244981
TI  - Proceedings of the 2nd Oslo Biennial Symposium on Lower Urinary Tract Physiology
      and Pathophysiology. Bladder contractility - normal emptying and emptying against
      obstruction. 17-18 November 1995.

PMID- 9244979
TI  - [Acute toxoplasmosis of the lymph nodes].

PMID- 9244982
TI  - [Surgical therapy of severe acute pancreatitis].
AB  - There is some evidence that the incidence of acute pancreatitis is increasing
      worldwide. Improved treatment concepts, especially in the severe course of the
      disease, have significantly reduced formerly high mortality. According to the
      different clinical courses it is of the utmost importance for the therapeutic
      approach to this disease to differentiate between mild (morphologically
      characterized as edema) and severe (intra- and extrapancreatic necroses) as early
      as possible. In this respect, contrast-enhanced CT scanning and the determination
      of so-called necrosis indicating parameters (e.g. C-reactive protein) have been
      established as the "gold-standard". While patients with acute edematous
      pancreatitis are successfully treated in a normal ward, patients with a proven
      necrotizing course of the disease should undergo intensive monitoring and maximum
      intensive care therapy in the ICU. Additionally, these latter patients should
      receive antibiotics which are capable of penetrating the pancreas and the
      pancreatic necroses in bactericidal concentrations. It seems more and more
      evident that only patients under this treatment regimen who develop infected
      pancreatic necrosis and sepsis are candidates for surgical intervention. Infected
      pancreatic necrosis can be easily diagnosed with a high level of safety and
      reliability by fine needle puncture and aspiration of pancreatic necrosis and
      fluid collections under imaging-guided procedures. Patients with sterile necrosis
      respond in most cases to intensive care therapy and in these patients the
      indication for surgery will be only exceptional. Surgery should be performed as
      late as possible to ensure sufficient demarcation of the necroses. In our
      experience the best surgical treatment modality for infected pancreatic necrosis
      is necrosectomy combined with postoperative continuous local lavage of the
      retroperitoneum. Mortality of severe acute pancreatitis has been reduced under
      this treatment concept to below 10%.

PMID- 9244983
TI  - [Consequences of cholestasis from the pathologist's viewpoint].
AB  - The present review summarizes extrahepatic obstructive cholestasis and its
      hepatic morphological sequelae. The first part focuses on early and late changes
      visualized in liver biopsies. In the second part, pathogenic mechanisms involved
      in liver fibrosis are discussed. A third section deals with the morphological
      differentiation of liver atrophy occurring in obstruction and secondary biliary
      cirrhosis. Biliary obstruction induces a wide array of typical early and late
      changes of liver morphology. They comprise the visible accumulation of bile in
      hepatocytes and macrophages, liver cell damage (cholate stasis; apoptosis),
      alterations of cellular organelles, cytoskeleton and junctions, portal tract
      edema with cellular infiltrates, ductular reaction, bile infarcts, bile
      extravasation and, in the later stages, fibrosis and partial nodular change. The
      pathogenesis of septal fibrosis appears to involve, besides fibroblasts,
      myofibroblasts probably derived from the Ito cell system. Myofibroblasts seem to
      closely follow proliferating ductules which, therefore, have a crucial role in
      hepatic tissue remodeling. There are considerable structural similarities between
      liver atrophy occurring in biliary and/ or portal vein obstruction and secondary
      biliary cirrhosis. In both situations partial nodular change ensues, but with
      preserved vascular relations. In addition, both changes are partially reversible
      in the early stages of the disease. Irreversible late stages of atrophy and
      secondary biliary cirrhosis are, therefore, maximum alterations of a similar,
      dynamic process, involving part of the liver in the first case and the whole
      organ in the second, depending on the level of obstruction.

PMID- 9244984
TI  - [Consequences of cholestasis from the hepatologist's viewpoint].
AB  - Chronic cholestasis is associated with a variety of symptoms and dysfunction of
      most organs. Among them, jaundice and pruritus are the first to be recognized,
      usually prompting the patients to see a physician. Besides the skin, however,
      cholestasis also affects, inter alia, the metabolism of plasma lipids and fat
      soluble vitamins, as well as bone and liver. In the following article the
      pathogenesis and therapy of metabolic disturbances and organ dysfunctions
      occurring frequently in patients with chronic cholestasis are discussed.

PMID- 9244985
TI  - [Surgery and cystic malformations of the bile ducts].
AB  - Bile duct cysts are usually diagnosed during infancy and childhood, although 20
      30% become symptomatic in adults, sometimes as late as the seventh decade of
      life. The Todani modification of the Alonso-Lej classification is now generally
      accepted and has clarified a previously confusing literature. Treatment is
      surgical: resectional rather than the traditional drainage procedures are
      indicated. This aggressive approach decreases but does not abolish the risk of
      cancer in the hepato-bilio-pancreatic tree. The patients must therefore be
      followed up for life.

PMID- 9244986
TI  - [Surgery in malignant obstructive jaundice: laparoscopic surgery--the future?].
AB  - The systematic staging of pancreatic cancer has facilitated exact evaluation of a
      patient's prognosis in recent years. Minimally invasive surgery, on the other
      hand, has produced new procedures which necessitate a distinct dichotomy between
      open, curative surgery and minimally invasive, palliative procedures. Diagnostic
      modalities facilitating an accurate assessment of resectability have to be found.
      Preoperative imaging and endoscopic techniques are only successful in about 50%
      of cases. Diagnostic laparoscopy is the only method for visualization of
      peritoneal metastases. The use of diagnostic laparoscopy and laparoscopic
      sonography raise the accuracy concerning resectability from 20% to between 75%
      and 100%. 33% up to 67% of patients deemed resectable by preoperative imaging
      show signs of unresectable cancer at laparoscopy and can be spared an unnecessary
      laparotomy. For these patients a choice of laparoscopic or endoscopic bypass
      techniques is available. The laparoscopic hepaticojejunostomy without sutures
      developed in Zurich has proven to be efficient in animal trials and will soon be
      implemented in clinical trials. A differentiated indication for laparoscopic
      bypass techniques and endoscopic stenting is necessary. The laparoscopic
      procedures should be employed in patients with a risk of duodenal obstruction or
      a projected mean survival of more than 6 months (stage III), while endoscopic
      stenting has already been established in the treatment of patients with a
      survival of less than 6 months (stage IV).

PMID- 9244987
TI  - [Docetaxel in lymphangiosis carcinomatosa].

PMID- 9244988
TI  - Annual Congress of the European Association for Endoscopic Surgery; Incorporated
      in the 1st Joint Euro-Asian Congress for Endoscopic Surgery. Istanbul, Turkey, 17
      21 June 1997. Abstracts.

PMID- 9244989
TI  - [From court medicine to forensic medicine].

PMID- 9244990
TI  - [Medical function in case of death: a final service to the patient and a key
      factor in legal safeguard].
AB  - The final service a doctor gives to his patients is to confirm death and to
      comfort the relatives. The unequivocal confirmation of death can, with complete
      justification, be considered the most important diagnosis so that it must be
      reached with every precaution. Apart from special conditions in intensive care
      units, where the guidelines of the Swiss Academy of Medical Sciences have to be
      followed with a view to using organs for transplantation, for example, the
      presence of reliable signs of death must absolutely be confirmed. The doctor who
      confirms death plays a key role in detecting so-called unusual deaths which
      require notification even in "clear", non-suspicious circumstances. This also
      applies to late deaths in hospital after an accident or other violence, where the
      clarification of the causal connection between this event and death is of
      decisive relevance. The detection or unequivocal exclusion of an outside
      influence in the death thus depend on the quality of the medical post-mortem
      examination and compliance with the duty of notification. The additional tasks
      falling to a doctor when he undertakes a legal inspection at the request of the
      examining authority in the case of an unusual death are discussed here only in
      passing. These tasks presuppose that the doctor has appropriate experience, which
      is why only official or district physicians from named institutions are accepted
      from the legal and forensic points of view in some Cantons.

PMID- 9244991
TI  - [Medical examination of sexual assault victims].
AB  - Two vital tasks have to be taken into account in the examination of a victim and,
      if necessary, of one or more suspects also: Firstly, medical evidence must be
      reliably obtained, and secondly, the knowledge based on the findings obtained
      must, as soon as the victim has decided to notify the police, be interpreted in
      an expert form so that apart from explaining the criminal matters to an examining
      judge, i.e. a medical layman, it allows a legal assessment of the incident.
      Doctors in general practice and working in hospitals may occasionally be
      entrusted with the examination of sexual assault victims. As a rule, a forensic
      examination is only performed if a victim has notified the police and this
      examination and opinion are requested by the police or court. The most pressing
      medical task in such examinations is to confirm the assault and to undertake
      correct documentation and exhibition of biological traces. As has been shown by
      regular questioning of doctors, there is considerable uncertainty concerning the
      nature and method of correct documentation of the findings as well as the
      techniques for preparing exhibits. Each institute of forensic medicine in
      Switzerland maintains a flying service and keeps doctors available for advice
      round the clock; they can best be contacted through the emergency numbers of the
      local police forces.

PMID- 9244992
TI  - [Medical procedures in gunshot injuries].
AB  - In this paper the basic knowledge about the morphology of gunshot wounds is
      presented, which should help the physician to answer the most important questions
      imposed on a criminal case. The paramount measures to be taken are the
      documentation of the gunshot wounds, the excision of the injury and separate
      debridement of each lip of the wound, the careful observation of the projectile,
      the cataloging of the victim's clothes and the omission of cleaning the hands of
      the victim. Some forensic aspects are demonstrated, particularly the professional
      discretion respectively the obligation to notify the authorities.

PMID- 9244993
TI  - [Biomechanics and injury prevention in road traffic].
AB  - The main predicting factor for the injury severity is "speed". This fact is
      predominantly important with regard to the protection of pedestrians and two
      wheelers. Today's safety features such as new steering and breaking systems, car
      body construction, seat belts, head restraints and crash helmets etc. let us
      sometimes overlook the hazards on the road. However, further improvements can be
      expected from advanced restraint system combinations, reinforced frontal and
      lateral car structures and padding, perhaps side air bags and automatically
      adjusted head restraint systems. Collision reconstruction and assessment of
      causality are needed, e.g., in cases of soft tissue neck injuries, questionable
      overrunning, walking direction of impacted pedestrians, uncertain belt or helmet
      wearing etc. Considerable legal problems arise if the causality is judged only
      from clinical point of view while the important criterion of collision mechanics
      is not taken into account in acceptable quantitative detail. Therefore it is
      recommended that determining the causality of a mechanical event should be left
      to specially trained professionals.

PMID- 9244994
TI  - [Problems in the assessment of driving capability in family practice].
AB  - More than half of the Swiss adult population possesses a valid driver's licence.
      To safely drive a car, certain medical demands are requested by law. Drivers of
      trucks, taxis and coaches and all drivers past the age of 70, must undergo a
      periodical medical examination. These examinations are usually performed by
      general practitioners. The most important legal foundations and the medical
      examination procedure are explained in this publication. Frequent diseases
      affecting the patient's driving ability such as poor vision, alcoholism, drug
      abuse, the early stages of dementia and other physical impairments are presented.
      Not to be neglected are the number of road traffic accidents resulting from
      medical reasons. The general practitioner is authorized to contact the
      authorities if he feels a patient is no longer capable of driving. For this
      reason, general practitioners should also be aware of the patient's driving
      capability other than during a periodical traffic examination. The individual's
      interests have to be carefully considered as opposed to that of society. The
      problems of general driving capability assessment performed by the general
      practitioner and possible procedures in case of patient's disagreement are
      presented.

PMID- 9244995
TI  - [Problems in traffic medicine in hospital and everyday practice: able to drive?].
AB  - On account of the right to mobility on the one hand and increased necessity for
      traffic safety on the other, physicians are more and more required to enhance
      involvement in traffic medicine. By the means of competent and professional
      acting, physicians should preventively contribute to traffic, safety [i.e. by
      informing about the influence of medical treatment on driving ability]. It is a
      matter of public interest to medically trace drives not able to drive. Proof of
      driving inability presupposes carefully done, standardized and reproducible
      clinical examination, along with the correct sampling of blood and urine. The
      knowledge of the most common pharmaceutical substances' effects on relevant
      traffic-related psycho-physical performances ensures timesaving medical
      examination and, due to the possibility to carry out more specific chemical
      analyses, important minimalization of the costly chemical analyses and therefore
      to less overall expenses. Finally, standardized proceeding makes possible medical
      realization of social responsibility and therefore improves jurisdiction.

PMID- 9244996
TI  - [Drug addiction--origin, development and pharmacological intervention].
AB  - The present essay on drug addiction deals, under the escort of empirical
      knowledges emanating from medico-legal toxicology, mainly with the behavioural,
      neurobiological, forensic and pharmacotherapeutical aspects of drug seeking and
      taking behaviour. The article emphasizes the idea that treatment of drug
      dependence [including that of the associated diseases and complications] should
      be performed according to the specific pharmacological and toxicological
      properties of the drugs involved. Furthermore, the treatment of drug dependence
      should be carried out in agreement with the individual needs of the patient, and
      in concordance with the multiple factors involved in the development and
      maintenance of drug addiction.

PMID- 9244997
TI  - [Treatment failure from the viewpoint of forensic medicine].
AB  - It is the nature of a disease that it may not only improve but also deteriorate
      even when under medical treatment. Medical treatment thus constitutes a high-risk
      activity. The great advances in medical diagnosis and treatment in recent years
      have increased this risk still further. The medical profession is becoming
      increasingly unsettled and worried about claims of treatment errors, not least
      because-of the increasing pressure from the public and media. This has wrongly
      led to the development of "defensive medicine" such as has already started to
      become established in the USA. The medical expert should stand as a mediator
      between medicine and law, and thus be in a position to clear up misunderstandings
      between the two disciplines with their different mind sets. For these reasons, a
      forensic specialist should be appointed as an expert whenever possible; he may be
      proposed to the examining judge as an additional expert in the field in question
      to answer special questions put to him. This article discussed the basis on which
      an expert medical opinion should be provided in relation to an injury arising as
      a result of a treatment.

PMID- 9244998
TI  - [Forensic hematology genetics--paternity testing].
AB  - In Switzerland paternity investigations are carried out using DNA analysis only
      since 1991. DNA patterns are inherited and only with the exception of genetically
      identical twins they are different in everyone and therefore unique to an
      individual. Hence DNA-systems are an excellent tool to resolve paternity
      disputes. DNA polymorphisms used for paternity diagnosis are length polymorphisms
      of the highly polymorphic VNTR loci [variable number of tandem repeats]. The most
      frequently applied systems are the DNA single locus systems. In addition to the
      DNA single locus systems the application of PCR (PCR = polymerase chain reaction)
      based DNA systems has increased particularly in difficult deficiency cases or in
      cases where only small evidential samples or partially degraded DNA are
      available. Normally four independent DNA single probes are used to produce a DNA
      profile from the mother, the child and the alleged father. A child inherits half
      the DNA patterns from its mother and the other half from its true biological
      father. If an alleged father doesn't possess the paternal specific DNA pattern in
      his DNA profile he is excluded from the paternity. In case of non-exclusion the
      probability for paternity is calculated according to Essen-Moller. When applying
      four highly polymorphic DNA single locus systems the biostatistical evaluation
      leads always to W-values exceeding 99.8% [= required value for positive proof of
      paternity]. DNA analysis is currently the best available method to achieve such
      effective conclusions in paternity investigations.

PMID- 9244999
TI  - [Sudden infant death].
AB  - Sudden infant death [SID] is defined as the "sudden death of an infant under one
      year of age that remains unexplained after a thorough case investigation,
      including performance of a complete autopsy, examination of the death scene and
      the review of the clinical history". This definition, given by the National
      Institute of Child Health and Human Development in the USA. recognized SID as a
      diagnostic entity, however, SID remains a pathological diagnosis of exclusion.
      SID-cases are divided into three categories: group 1 in which autopsy does not
      reveal any cause of death, group 2 in which postmortem findings are not
      sufficient to be the cause of death; group 3 in which the death is adequately
      explained, is classified as "non-SID". The purpose of the study was to analyse
      the situation about SID over a 25-year period, from 1969 through 1993, looking
      for changes in frequency and developmental trends. The study includes 364 SID
      infants which were examined according to a standard method. Histological,
      microbiological, virological and immunological studies were performed and data of
      the death scene investigation and of the clinical history were collected, 284
      infants who had died due to clinical diseases served as one control group, a
      second group consisted of 6397 newborns of the city of Zurich. Of the SID
      infants, almost every third infant [29%] was grouped in group 1, more than half
      of the infants [52%] with signs of mild infections in group 2, whereas almost
      every fifth child [19%] was grouped in group 3. With regard to epidemiological
      parameters the peak of mortality was found at about three months of age; the
      percentage of boys and twins, of third and later born infants was higher compared
      to the general population. SID probands were born twice as often in October as in
      March. The percentage of mothers of first, second and third born SID-infants at
      an age younger than 20, 22 and 24 years was higher compared to the general
      population. All these parameters were also found in group 3. The risk of familial
      recurrence in group 1 and group 2 was 0.8%. Between 1969 and 1993 the rate of SID
      deaths dropped from 1.1 to 0.9 per thousand live births, whereas SID as a
      percentage of postneonatal mortality increased to 34 per cent.

PMID- 9245000
TI  - [The functional morphology of the epithelial barrier of the oral mucosa].
AB  - Modern notions on the morphology and function of the epithelial barrier of the
      buccal mucosa are discussed. The basis of this barrier is the epithelial layer,
      partially covered with horny layer, of a regular thickness and permeability,
      constantly regenerating, and casting off the injured superficial layers.
      Nonspecific antibacterial humoral factors (produced by the epithelium and
      salivary glands) play an important role in the barrier mechanisms, as well as
      nonspecific cellular mechanisms of defense, due to the presence of
      intraepithelial granulocytes and monocytes, specific immune humoral and cellular
      mechanisms including the system of antigen-presenting dendrite cells and
      lymphocytes, and flow of the saliva containing nonspecific and specific
      antibacterial factors. The barrier function of the epithelium is provided for by
      constant interactions between various specific and nonspecific cellular and
      humoral defense mechanisms.

PMID- 9245002
TI  - [The use of plasmapheresis in treating recurrent aphthous stomatitis].
AB  - Plasmapheresis was used in multiple-modality treatment of 33 patients with
      chronic relapsing aphthous stomatitis. Plasmapheresis was administered on an
      inpatient basis in an intermittent mode with exfusion of up to 1 liter of plasma
      per session, 1-3 sessions per course. The efficacy of treatment was assessed from
      the time course of clinical picture, time of onset of remission and its duration,
      and metabolic and immunity parameters. Plasmapheresis improved the general status
      of the patients, accelerated epithelialization of the buccal mucosa, helped
      attain prolonged remissions, and ameliorated the homeostasis parameters.

PMID- 9245001
TI  - [A clinical and experimental validation of the use of Stimuloss in patients with
      chronic generalized periodontitis].
AB  - The pharmacological effect of hydroxyapatite and a composition based on it in the
      form of Stimulos sponge has been studied in human osteogenic tissue culture.
      Hydroxyapatite stimulated the biosynthetic processes in the cells. Addition of
      chlorohexidine and thymogen to the composition in order to increase its
      antibacterial activity did not decrease the osteoinductive properties of the
      drug. Trials of Stimulos in 66 patients with chronic generalized periodontitis
      demonstrated its high efficacy, particularly of the compositions containing
      immunostimulants: inflammation disappeared and the height of alveolar osseous
      tissue increased, as did bone compactness.

PMID- 9245003
TI  - [Solcoseryl Dental Adhesive Paste in the treatment of the oral mucosal wounds
      following the implantation of endosseous implants].

PMID- 9245004
TI  - [The classification of diseases of the temporomandibular joint].
AB  - There were 2040 patients with temporomandibular joint (TMJ) diseases in the
      investigation including clinical, physiological, X-ray methods of research,
      contrast arthrotomography, computer arthrotomography and magnetic resonance
      tomography. The changes of structure in different lesions were estimated. The
      result of received data was elaboration of classification of TMJ internal
      derangements with estimation of clinical forms in according with structural
      changes and characteristics of syndromes.

PMID- 9245005
TI  - [The treatment of temporomandibular joint involvement in Bechterew's disease].
AB  - The authors analyzed experience gained in the treatment of the temporomandibular
      joint involvement in Bechterew's disease. Three groups of this complication were
      distinguished and treatment protocols offered for all of them. Drugs used in the
      treatment are compared. Surgical treatment of an ankylosed joint using a titanium
      endoprosthesis of a half-joint is described.

PMID- 9245006
TI  - [The surgical correction of traumatic deformities of the orbit in naso-fronto
      orbito-cribriform fractures].
AB  - J. Raven's (1992) classification was used in the treatment of patients with
      multiple fractures of the face associated with contusions, brain concussions, and
      injuries to the skull vault and base. According to this classification, all
      injuries of the cerebral and facial skull are classified as types I, II, and
      subtype Ia. Use of this classification became possible due to introduction of
      computer-aided tomography. A clinical example of a possible surgical correction
      of the orbit in a patient with type II fracture is presented.

PMID- 9245008
TI  - [The correction of a protruding tip of the nose].
AB  - Burian's operation (dissection of the cartilagenous segments from the median and
      lateral parts of the alar cartilage, distant from the deformation) often used for
      repair of deformations of the tip of the nose helps attain good remote results in
      57% of cases and satisfactory in 43%. The authors propose a method directed at
      the deformation proper: isolation and removal of segments of cartilagenous
      transfer of the medial parts to lateral and removal of the cartilagenous segments
      from the lateral parts of alar cartilages. Forty-four patients were operated on
      using this method, good results were attained in 40 (90%), satisfactory in 4
      (10%) patients.

PMID- 9245007
TI  - [The prevention and treatment of complications related to the removal of the
      mandibular third molar when it is retained].
AB  - The lower third molars were removed in 52 patients by the method developed by the
      authors because of these teeth's retention or half-retention. Control group
      consisted of 22 patients in whom the teeth were removed traditionally. In 35
      patients of the main group with acute inflammations of soft tissues adjacent to
      the tooth to be removed the operation was performed without preliminary arrest of
      inflammation. Bone cavity formed after removal of the tooth was filled with
      hydroxyapatite. In some cases Maillefer turbine drill or Lancet high-intensity
      laser device were used for cutting the diseased tooth into pieces. After surgery
      laser and antibiotic therapy were carried out. Four (7.7%) patients with
      inflammations before surgery developed complications. The operation wound healed
      in 9-10 days in patients with inflammations and in 7-8 days in those without
      inflammations, in contrast to the controls, in whom recovery ensued only in 4-6
      weeks. Hence, the new method is recommended for clinical use irrespective of
      inflammatory changes in the adjacent tissues.

PMID- 9245009
TI  - [A method for preparing the abutment teeth for resin-bonded bridge dentures and
      resin-bonded facings (veneers) and its anatomical validation].
AB  - This article describes a relatively new modality of tooth preparation techniques
      used in Maryland bridges and veneers. Tooth preparation based on enamel thickness
      data is routinely recommended.

PMID- 9245010
TI  - [The nature of the action of chemical substances on the activity of the
      microflora in soft dental deposits].
AB  - Effects of the principal mineral and mineralizing components of the saliva,
      nutrient organic acids (carbohydrate and some others substances' metabolites) on
      the activity of microflora of soft dental deposit were studied in vitro. The
      inhibitory effect was assessed visually from the appearance or absence of deposit
      coating, pH measurement, and by photo- and nephelometry. Concentrations of lactic
      acid and sucrose were measured. The inactivating effects of the reagents were
      assessed by double control: qualitative, by comparing the specimen with the optic
      density of the extract from aqueous suspension of the deposit, and time control,
      by comparing the specimen with the optic density of extracts from deposit
      suspensions directly after mixing with the medium. Acid medium was found to block
      the formation of soft dental deposit and inhibit the production of lactic acid by
      bacterial deposit. Hence, weakly acid gargle is recommended as an effective and
      physiological measure preventing cariogenic situation resultant from the intake
      of easily fermenting carbohydrates.

PMID- 9245011
TI  - [The principles of designing stump pin inserts in pathological tooth abrasion].
AB  - A total of 278 patients aged 40 to 67 with pathological abrasion of hard dental
      tissues were treated. Decreased occlusion height was diagnosed in 152 (54.67%) of
      these. In 146 patients abutment teeth under permanent dentures were fixed with
      cast stump pin insertions. Complications occurred in 9.6% cases: perforation of
      the wall of the root canal (1.14%), failure of cementing (3.98%), fracture of the
      root (1.14%), breaking of a fragment of the root at the neck of the tooth
      (2.84%), and inflammations of the marginal periodontium (0.57%). In order to
      prevent these complications and improve the fixation of cast stump pin insertion,
      we used our modifications of cast stump pin insertions (n = 394) for anterior and
      lateral teeth. The incidence of complications decreased more than 5 times. Follow
      up of 2 to 8 years showed 1.78% of complications.

PMID- 9245012
TI  - [The Endodontia Automated Computer System for the differential diagnosis and
      laser therapy of dental caries, pulpitis and periodontitis].

PMID- 9245013
TI  - [The x-ray diagnosis of teeth with difficult eruption and improper positioning].

PMID- 9245014
TI  - [A fragmented ribbon splint for the treatment of tooth dislocations].
AB  - A simple, reliable, and easy-to-make splint is proposed for immobilization of the
      dislocated upper and lower incisors. The splint does not prevent correct
      occlusion, is hygienic and atraumatic. The process of immobilization of the
      dislocated tooth is accelerated if half-products are available. The splint
      consists of processes for fixation and the part fixing the tooth, its vestibular
      part involves the palatal surface of the tooth and is finished with an occlusion
      pad. The splint is fixed with bronze-aluminium wire to 2-3 healthy teeth on both
      sides of the dislocated tooth.

PMID- 9245015
TI  - [Means for improving the training of orthodontists].

PMID- 9245016
TI  - [The marketing of dental goods and services].

PMID- 9245017
TI  - [Iakov Emmanuilovich Bronshtein (on the centenary of his birth)].

PMID- 9245018
TI  - [A list of author dissertation abstracts (candidate and doctoral) deposited in
      the State Central Medical Research Library and the Central Research Institute of
      Stomatology in 1995].

PMID- 9245019
TI  - [Quality assurance and assessment of medical technology in surgery].

PMID- 9245020
TI  - [Postoperative wound infections].

PMID- 9245022
TI  - [A gastroenterologist on the Internet].

PMID- 9245021
TI  - [European standards for cardiovascular implants].

PMID- 9245023
TI  - [Duodenal diverticula].
AB  - Duodenal diverticula occur in 0.016 to 5.19% of patients undergoing
      roentgenographic investigation of the upper gastrointestinal tract. They are
      classified into extraluminal and intraluminal types and are usually found near
      the papilla of Vater. The majority of these cases are asymptomatic. These
      diverticula occasionally result in the obstruction of the biliary and/or
      pancreatic ducts, haemorrhage or perforation. Symptomatic cases may require
      endoscopic or surgical intervention. The management should be individualized to
      the kind of complication, type, and location of the diverticulum. Surgical
      procedures in this area may be technically difficult and associated with high
      mortality and morbidity. Elective treatment of uncomplicated duodenal diverticula
      is usually not justified. The difficulties in identifying these lesions as the
      source of symptoms are emphasized.

PMID- 9245024
TI  - [Somatic illness in psychiatric patients].
AB  - Psychiatric patients are a vulnerable group in society and have been shown to
      suffer from a wide range of somatic diseases when admitted to the psychiatric
      department. During a three month period we examined 174 newly admitted
      psychiatric patients with the purpose of investigating 1) the frequency of
      somatic illness, 2) the value of routine blood tests as a screening tool for
      somatic illness and 3) a possible causality between somatic disease and
      psychiatric illness. Fifty percent of the patients suffered from a somatic
      disease and 31% of the patients had a previously undiagnosed disease. The somatic
      disease was found to be the main cause of admission in 16% of the patients. Older
      patients and patients with alcohol abuse were found to have the highest
      prevalence of somatic disease. In conclusion, we found no indication for a
      screening programme of blood tests, but recommend that selected blood tests based
      on the clinical examination and history of the individual patient should be
      taken. Psychiatric patients have a high prevalence of somatic disease, and it is
      important to direct clinical attention towards this when giving care to
      psychiatric patients.

PMID- 9245025
TI  - [Profile of the strain on the psychiatric departments in the county of Arhus].
AB  - In order to describe the psychiatric morbidity in the population of the county of
      Arhus, the following census study was performed. The psychiatric hospital
      services in the county of Arhus are divided into five separate units. The
      population in each of the catchment areas was checked in The National Psychiatric
      Case Register, which contains information on all admissions to psychiatric
      hospitals in Denmark since 1970 and all referrals to psychiatric community
      services since 1995. The study describes the prevalence of former or present
      patients living in each of the five units. The study focuses on patients
      suffering from schizophrenia, affective disorders or disorders due to abuse of
      alcohol or drugs. The study finds an uneven distribution of former or present
      patients in the county suffering from the above mentioned disorders, indicating
      variation in the extent to which psychiatric treatment is needed.

PMID- 9245026
TI  - [Mortality in adults with asthma. Results from the Osterbro study].
AB  - A prospective analysis of overall and cause-specific mortality in subjects with
      self-reported asthma was undertaken using the data from The Copenhagen City Heart
      Study. A sample of 13,540 individuals selected from the general population was
      followed for 17 years. Survival of subjects with self-reported asthma was
      significantly poorer than that of non-asthmatics, the excess mortality being
      limited to pulmonary mortality. After statistical adjustment for age, length of
      school education, and smoking, women with asthma had a 1.7 higher risk of dying
      than women without asthma. The similar risk for men was 1.5. Inclusion of one
      second forced expiratory volume, in % predicted, in the mortality analyses showed
      that the increased risk of death associated with asthma was mediated mainly
      through reduced lung function. We conclude that in the general population self
      reported asthma is associated with a slight excess of mortality, mainly due to
      respiratory disease.

PMID- 9245027
TI  - [Decreased pain threshold and tolerance in patients with chronic tension
      headache].
AB  - Nociceptive processing was studied in 40 patients with chronic tension-type
      headache and in 40 healthy controls. We found that pericranial tenderness
      recorded by manual palpation was considerably higher in patients than in controls
      (p < or = 0.0002). Pressure pain detection and tolerance thresholds recorded in
      the finger, by means of a pressure algometer, were significantly lower in
      patients than in controls (p < or = 0.0009), and a non-significant similar trend
      was observed in the temple (p < or = 0.12). Detection and tolerance thresholds
      were decreased to a similar degree in patients compared with controls, and pain
      thresholds recorded in the finger and in the temple were highly correlated (r =
      0.84, p < 0.0001). The electrical pain threshold at the labial commissure, by
      means of an electrical stimulator, was significantly decreased in patients
      compared with controls (p = 0.03). All of the examined pain thresholds were
      significantly correlated to the pericranial tenderness recorded by palpation (r =
      -0.35 to -0.53, p < or = 0.03). We conclude that the present finding of a general
      hypersensitivity to pain stimuli in chronic tension-type headache indicates that
      central factors play an important role in the pathogenesis of this disorder.

PMID- 9245028
TI  - [Smoking reduces the biological capacity of conception. Results from a European
      multicenter study. The European Study Group on Infertility and Subfecundity].
AB  - The aim of the study was to examine the impact on subfecundity of male and female
      smoking at the start of a couple's waiting time to a planned pregnancy. Two types
      of designs were applied: a population based sample of women aged 25-44 years of
      age and a consecutive sample of pregnant women. Both studies were conducted
      within well-defined geographical regions in a number of European countries and
      data were collected by personal interviews in the population-based sample and by
      interview or self-administered questionnaires in the pregnancy study. A total of
      10,665 couples participated in the study. Data on possible risk factors for
      infertility and subfecundity were collected at the start of the pregnancy
      planning, and fecundity was estimated by using time from the beginning of
      unprotected intercourse to a pregnancy, which survived at least 20 gestational
      weeks. Only couples who planned a pregnancy were included in the analyses. The
      results showed remarkably coherent associations between female smoking and
      subfecundity in each individual country and in all countries put together. In the
      population sample the odds ratio for subfecundity in the first pregnancy was 1.7
      (95% c.l. 1.3-2.1 at the upper level of tobacco consumption) and during the most
      recent waiting time to pregnancy the odds ratio was 1.6 (95% c.l. 1.3-2.1).
      Results based on the pregnancy sample were similar with an odds ratio of 1.7 (95%
      c.l. 1.3-2.3). No significant association was found between male smoking and the
      couple's fecundity.

PMID- 9245029
TI  - [The dangerous kitchen].
AB  - A case is presented where a small girl, when playing in the kitchen, tripped and
      fell over the opened door of the dishwashing-machine, thereby hitting a sharp
      knife and acquiring a long, but rather superficial wound at the right side of the
      neck. It is strongly recommended to be extremely careful when children are
      playing in the kitchen, and never to leave sharp items in the dishwasher with the
      pointed end upwards.

PMID- 9245030
TI  - [Abdominal actinomycosis. Two cases from a department of surgery].
AB  - Two case stories of abdominal actinomycosis are described. Knowledge and proper
      treatment of this bacterial disease are important in order to prevent recurrent
      abscesses or major surgical operations.

PMID- 9245031
TI  - [Myths about overmortality of Danish women].

PMID- 9245032
TI  - [Acute admissions in pediatric psychiatry].

PMID- 9245033
TI  - [Gestational diabetes mellitus].

PMID- 9245034
TI  - [Rheumatoid arthritis. Drug therapy].

PMID- 9245035
TI  - [Nephrology on the Internet].

PMID- 9245036
TI  - [Radiological changes in chronic recurrent multifocal osteomyelitis].
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a well-established rare
      clinical and radiographical disease entity, occurring mainly in children and
      adolescents with a female predominance. It is predominantly located to tubular
      bones followed by the clavicle and the spine, and other locations are rare. The
      diagnosis is usually based on a characteristic fluctuating benign course and
      conventional radiography, if necessary supplemented by microbiological and
      histopathological examinations to exclude infectious diseases, tumour or tumour
      like lesions. It is important to make the diagnosis in order to avoid unnecessary
      additional diagnostic procedures and give an appropriate therapy. To do this it
      is necessary to know the radiographic features, which are reviewed here.

PMID- 9245037
TI  - [Heyde syndrome].
AB  - Since Heyde in 1958 suggested the association of aortic stenosis and significant
      gastrointestinal bleeding, the syndrome has been a matter of debate. After
      analysing the literature it is concluded 1) that a prospective well designed
      study is needed, but the Heyde syndrome seems to exist, since the
      gastrointestinal bleeding caused by angiodysplasia ceases after valve replacement
      in spite of the fact that the angiodysplasia remains, 2) that the cause of the
      association between aortic stenosis and bleeding from angiodysplasia is still
      uncertain, but impaired aggregability of thrombocytes does not seem to be the
      explanation and 3) that the treatment should be replacement of the stenotic
      aortic valve by either a mechanical or biological valve.

PMID- 9245038
TI  - [Changes in glucose metabolism in gestational diabetes mellitus during and after
      pregnancy].
AB  - Twenty-nine pregnant women with gestational diabetes mellitus (GDM) diagnosed
      before the 34th gestational week had three intravenous glucose tolerance tests
      (IVGTT) performed during pregnancy and a follow-up with OGTT post partum. The
      women with a normal OGTT post partum had a significant decrease in fasting serum
      glucose from the 33rd to the 38th week in pregnancy (4.8-->4.0 mmol/l, p < 0.05).
      However, the women with a diabetic/borderline OGTT showed no decrease in fasting
      serum glucose during the same period (5.1-->5.0 mmol/l). The K-value (the
      diminution rate of blood glucose) of the IVGTT in week 38 was significantly lower
      in women with puerperal diabetic/borderline OGTT compared with women with a
      normal post partum OGTT (1.05 +/- 0.07 vs. 1.32 +/- 0.08 -10(2) x mmol/l x min-1,
      respectively, p < 0.05). Diabetic or borderline diabetic OGTT in the first week
      post partum was significantly associated with a decrease in the K-value from week
      33 to 38 (p < 0.05). Early diagnosis of GDM was found to be associated with a
      pathological OGTT post partum (p < 0.05). Five of 22 women (23%) with previous
      GDM had a diabetic and one (5%) a borderline OGTT at follow-up four to thirteen
      months post partum. High fasting serum glucose levels during the last trimester
      in GDM can identify the women at risk of diabetic/borderline OGTT post partum.

PMID- 9245039
TI  - [Prognostic value of insulin-like growth factor I-IGF-I--and its binding protein
      IGFBP-3 in alcoholic liver disease].
AB  - IGF-I is a single polypeptide chain with important anabolic and endocrine
      activities. The liver is the major source of IGF-I and its binding protein, IGFBP
      3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with
      chronic liver disease and correlate with the severity. The aim of this study was
      to assess the additional prognostic value of IGF-I and IGFBP-3 in patients
      entered in a large multicentre study (EMALD). Three hundred and thirty-seven
      patients with alcoholic liver disease were studied in a randomised placebo
      controlled trial of malotilate with a mean follow-up period of 569 days (range: 7
      1544). A multivariate Cox regression analysis of pertinent clinical and
      biochemical variables revealed a significant independent prognostic value of
      years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases,
      serum creatinine, and immunoglobulin M (IGM). When IGF-I or IGFBP-3 were added
      into this model, a Cox regression analysis showed that either had a significant
      independent prognostic value. As IGF-I and IGFBP-3 were closely correlated, they
      contained almost the same prognostic information. Inclusion of IGF-I gave these
      results: IGF-I (p < 0.03), alcohol intake (p < 0.02), coagulation factors 2, 7,
      and 10 (p < 0.01), creatinine (p < 0.001), and IgM (p < 0.01) contained
      independent prognostic information. Inclusion of IGFBP-3 gave these results:
      IGFBP-3 (p < 0.02), alcohol intake (p < 0.05), coagulation factor 2, 7, and 10 (p
      < 0.01), creatinine (p < 0.001), and IgM (p < 0.02) were independent predictors
      of survival. In conclusion IGF-I or IGFBP-3 provides important additional
      information on survival in patients with alcoholic liver disease.

PMID- 9245040
TI  - [Bone loss during low dose glucocorticoid treatment in patients with polymyalgia
      rheumatica. A double-blind, prospective comparison between prednisolone and
      deflazacort].
AB  - The aim of the study was to compare the long term effects of low dosage
      prednisolone or deflazacort treatment on bone mass in patients with polymyalgia
      rheumatica. The subjects were 30 patients with newly diagnosed polymyalgia
      rheumatica, who were allocated to treatment with prednisolone or deflazacort.
      Bone Mineral Content (BMC) was measured in the lumbar spine (L-BMC) and distal
      forearm (A-BMC) before treatment and three, six and 12 months after the start of
      treatment. After three months the decrease in L-BMC was significantly greater in
      the deflazacort group than in the prednisolone group (p < 0.05), but at six and
      12 months there was not a significant difference between the two groups. There
      was a significant loss of BMC in all patients after 12 months: a 6.4% loss in L
      BMC and a 1.8% loss in A-BMC. In conclusion, this low dose study failed to reveal
      any calcium sparing property of deflazacort compared with prednisolone.

PMID- 9245041
TI  - [Effects of nitrogen oxide donor glyceryl trinitrate on pressure pain threshold
      in humans].
AB  - The purpose of the present study was to examine the effect of the nitric oxide
      (NO) donor glyceryl trinitrate (GTN) on nociceptive thresholds in man. On two
      different study days twelve healthy subjects received a stair case infusion of
      GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min 20 min each dose) or placebo in a
      randomized double-blind cross-over design. Before the infusion and after 15 min
      of infusion on each dose, pressure pain detection- and tolerance thresholds were
      determined by pressure algometry in three different anatomic regions (finger, a
      temporal region with interposed myofascial tissue and a temporal region without
      interposed myofascial tissue). Relative to placebo the three higher GTN doses
      induced a decrease in both detection- and tolerance-thresholds in the temporal
      region with interposed myofascial tissue. No such changes were observed in the
      two other stimulated regions. These results could reflect central facilitation of
      nociception by NO. However, convergence of nociceptive input from pericranial
      myofascial tissue and from cephalic blood vessels dilated by NO may provide a
      more likely explanation.

PMID- 9245042
TI  - [Children and adolescents under 18 years of age admitted to a psychiatric
      department for adults].
AB  - Now and then children and adolescents are admitted as emergencies to adult
      psychiatric wards. The reasons for these admissions are frequently pronounced
      aggressiveness, behavioural problems, and threat of suicide or intended suicide.
      The aim of the study was to describe the cause of admission for those children
      and adolescents (younger than 18 years) that in the period concerned were
      admitted as emergencies to the adult psychiatric ward in Frederiksberg, Denmark.
      During the ten-year period concerned there were 42 emergency admissions.
      Compulsory measures according to the mental health act were used in one-third of
      the admissions. Forty percent of the admissions lasted more than one month. An
      arrangement for treatment after discharge was not achieved in one-third of the
      admissions. The most common diagnoses were adjustment disorder and conduct
      disorder. On the basis of this retrospective review the need for a locked
      adolescent ward is considered to be a relevant part of an emergency psychiatric
      service. There is an ethical problem in those cases where children and
      adolescents cannot be motivated for treatment after discharge.

PMID- 9245043
TI  - [Legionella infection with rhabdomyolysis].
AB  - Rhabdomyolysis complicating infection with Legionella pneumophila has previously
      been reported and may in some cases have led to acute tubular interstitial
      necrosis. We report a case of severe Legionnaires' disease complicated with
      rhabdomyolysis, myoglobinuria and neurological symptoms. Treatment with
      erythromycin and rifampicin was initiated early in the course of disease. The
      myoglobinuria was treated with forced diuresis and alkanization and renal failure
      did not develop. The frequency of rhabdomyolysis as a complication to
      Legionnaires' disease is not known. In addition, the pathogenesis and possible
      risk factors have not yet been determined. Considering the seriousness of this
      complication and until further investigations have been performed we recommend
      that routine determinations of creatine phosphokinase are performed in the
      evaluation of these patients.

PMID- 9245044
TI  - [Recurrent infantile digital fibromatosis].
AB  - In reflection of a current case, the latest literature concerning recurring
      infantile digital fibromatosis (Reye's tumour) are summed up. It is a non
      malignant, rarely encountered tumour observed in children, appearing on the hands
      and feet. The tumour is almost exclusively diagnosed before the age of three. The
      etiology is unknown. Approximately 100 cases have been reported in the
      literature. Eosinophilic inclusion bodies near the nucleus of the tumourcells are
      pathognomonic. According to the latest literature, the content of the inclusions
      is mostly actin filaments between which the formed elements of the cell are
      entrapped. Previous treatment was repeated excision of the recurring tumours,
      until spontaneous cessation of disease activity. According to the latest
      literature, a more conservative treatment is recommended, because the fibromas
      often regress spontaneously over few years. Therefore surgical treatment is only
      needed in rare cases with aggressive or uncontrollable growth of the fibromas.

PMID- 9245046
TI  - [New atypical neuroleptics--what to believe?].

PMID- 9245045
TI  - [Proguanil].

PMID- 9245047
TI  - [Mycophenolate mofetil. A new immunosuppressive agent in transplantation
      therapy].

PMID- 9245048
TI  - [The etiological structure of the causative agents of inflammatory nonspecific
      urological diseases and the dynamics of their resistance to the widely used
      antibiotics].
AB  - Of late, a trend to a marked loss in antibacterial efficacy of some antibiotics,
      for instance gentamycin and carbenicillin, is noted. This is due to changes in
      the microflora composition and sensitivity to antibiotics, an increase in the
      number of polyresistant microorganism strains. As gentamycin is effective now
      only against E. coli, it is not appropriate to use it in urological hospitals.
      Cefatoxim (claforan), on the contrary, retains its high antibacterial potential
      and becomes a basic antibiotic in the treatment of bacterial infections in
      urology. Continuous microbiological control is needed over fluoroquinolones
      microflora resistance to which is on the increase. Correction of therapy may be
      also required in the presence of such pathogens as Pseudomonas aeruginosa.

PMID- 9245049
TI  - [Extracorporeal lithotripsy of stones in the single kidney].
AB  - The authors used shockwave lithotripsy (SWL) in 130 patients with solitary kidney
      to crush renal calculi. Valid policy in preoperative drainage may result in a
      significant reduction of the occurrence of postoperative obstructive
      complications. It was only 11.5%. A valid choice of sparing regimen of crushing
      kidney and prepelvic ureter calculi help prevent hematomas, a severe complication
      of early postoperative period. No cases of this complication were seen in the
      study. A significant renal function failure in early postoperative period was not
      recorded. A 2.5--5-year follow-up in 21 patients has found that in 61.9% of
      patients renal function recovered or remained stable, in 38.1% of patients renal
      function declined. This was due to deterioration of the underlying disease
      (chronic pyelonephritis, frequent recurrences of lithogenesis).

PMID- 9245050
TI  - [The use of xidifon for the correction of phosphorus-calcium metabolism in
      patients in the terminal stage of chronic kidney failure who are on programmed
      hemodialysis].
AB  - Correction of impaired phosphoric-calcium metabolism was performed in 15
      hemodialysis patients with terminal chronic renal failure (TCRF). For this
      purpose a synthetic analogue of pyrophosphoric acid xidiphone produced in Russia
      was used (2% aqueous solution 1 tablespoon 3 times a day 0.5 h before meal for 2
      3 months). Prior to and in the course of xidiphone treatment all the patients
      received calcium gluconate (1 g x 3 daily), polyvitamins, on-demand digoxine.
      Measurements of serum concentrations of urea, potassium, sodium, total calcium,
      alkaline phosphatase activity demonstrated xidiphone-related normalization of
      serum total calcium, serum activity of alkaline phosphatase, a mild rise of
      sodium. The results say in favor of using xidiphone in the TCRF patients.

PMID- 9245051
TI  - [Endoscopic ureterolithotripsy with the holmium laser].
AB  - One of the clinical and experimental investigations performed in the urological
      clinic of the Moscow Medical University and Research Institute of Urology aimed
      at elucidation of Ho-YAG-laser potential in endoscopic lithotripsy (EL). Russian
      Ho-YAG laser surgical units CTH-10 and LLT-3 with wave length 2.09 mu were
      employed. The studies showed that the developed laser units satisfied relevant
      medical and technical requirements. Low depth of laser impulse penetration (0.4
      mm) obtained at EL warrants safety of the adjacent tissues which is essential in
      crushing fixed ureteroliths in the presence of severe inflammation in the
      ureteral wall. The conclusion is made that Ho-YAG laser EL is an effective
      treatment of ureteroliths. Further tests for EL efficacy in affections of the
      upper urinary tracts are advocated to define a proper place of EL in endoscopic
      urology.

PMID- 9245052
TI  - [The use of Categel with lidocaine in urology].
AB  - Efficacy of catejel with lidocaine and catejel C has been assessed in patients
      subjected to cystoscopy, bougienage, catheterization and urethroscopy.
      Postcystoscopy and urethroscopy patients were divided into 3 groups. The patients
      subjected to cystoscopy and bougienage with the use of narcotic or non-narcotic
      analgetics, cystoscope or bougie lubricated with vaseline or glycerin were
      allocated in group 1, with the use of catejel with lidocaine in group 2,
      combination of the above two technique in group 3. Pain appeared the least in
      group 3 patients, urethral fever arose in 7, 1 and 1 patients, respectively.
      Sharp image at cystoscopy was achieved in 96% of cases. It is shown that catejel
      with lidocaine provides good pain relief and prevents many complications.
      Combination of catejel with lidocaine and analgetics reduces pain to minimal
      values.

PMID- 9245053
TI  - [The disseminated intravascular coagulation syndrome in urological diseases].
AB  - The authors consider causes and mechanisms underlying DIC syndrome onset in
      complications of urological diseases. The syndrome may originate from azotemia
      induced intoxication, injury to the kidneys and urinary tracts, complications of
      surgical interventions. Etiologically and pathogenetically validated approaches
      to DIC syndrome treatments, their regimens, combinations and dosages are
      presented.

PMID- 9245054
TI  - [Outpatient urodynamic monitoring in the diagnosis of subclinical forms of a
      urination disorder in women].
AB  - The authors studied potentialities of outpatient urodynamic monitoring in
      diagnosis of subclinical urination defects in females. The examination was made
      of 31 females aged 25-55 years (mean age 43.8 years) with complaints of
      pollakiuria, precipitant urination. Laboratory urodynamic investigation combined
      retrograde cystometry, profilometry and uroflowmetry (Jupiter 8000 Video produced
      by WIEST) and was followed by urodynamic monitoring (CAMSYS 6300 by WIEST).
      Standard combined urodynamic evaluation registered normal urodynamic parameters
      in 17 females, unstable urethra in 4, unstable detrusor in 7, unstable urethra
      and detrusor in 3 patients. The curves devised on the basis of the outpatient
      urodynamic monitoring data indicated that; normal urodynamics, unstable urethra,
      unstable detrusor, detrusor-sphincter dyssynergia, combined instability of
      urethra and detrusor, unstable detrusor plus detrusor-sphincter dyssynergia in 4,
      10, 7, 3, 2, 2 females, respectively. 3 cases were ineligible. The above
      investigation promoted accurate diagnosis in 41.9% of cases. Outpatient
      monitoring is a method of choice in diagnosis of subclinical urination disorders.

PMID- 9245055
TI  - [Plastic repair of the anterior abdominal wall in bladder exstrophy].
AB  - In 1987-1993 surgical treatment for exstrophy of the bladder was performed in 35
      children at the age 8 months--3 years. All the patients underwent one-stage
      transplantation of the ureters into the semi-isolated segment of the sigmoid
      colon with antireflux protection of the ostia, bladder extirpation and repair of
      the anterior abdominal wall. The most difficult stage of the intervention is
      repair of the abdominal wall defect after removal of the large bladder. Related
      complications arising in 16% of the surgical patients impose the problem of the
      technique of safe filling of the abdominal wall defect. In 16 patients with large
      bladder its demucosation was followed by strengthening of the detrusor muscles
      with the help of interrupted sutures with fixation to underdeveloped oblique
      abdominal muscles. The skin defects was filled by raised movable skin flaps on
      both sides of the divided pubis. The above technique reduced the number of
      postoperative complications three times. Intestinal eventration was not observed.
      The wound suppuration and partial defect of the sutures occurred in 1 case. The
      rest 15 children exhibited healing with minimal scarring and good cosmetic
      effect.

PMID- 9245056
TI  - [The temperature regimens for transurethral thermotherapy in treating benign
      prostatic hyperplasia].
AB  - Transurethral microwave thermotherapy (Prostalund unit made by Lund Instruments)
      was given to 49 patients with benign prostatic hyperplasia. The prostate was
      heated transurethrally for 60 min. Only one procedure was performed. Temperature
      regimens were different: prostatic tissue was heated to 50 degrees C, 55 degrees
      C and 60 degrees C (14, 17 and 18 patients, respectively). The response assessed
      6 months after the treatment was the best in the group on the highest temperature
      regimen.

PMID- 9245057
TI  - [The effect of prostatilen on the hemostatic indices in chronic prostatitis (a
      clinical and experimental study)].
AB  - Prostatilen effects on hemostasis were studied in 120 intact and 240 chronic
      prostatitis rats, 34 patients with chronic prostatitis. Intact rats responded to
      prostatilen by inhibition of platelet-vascular and coagulation hemostatic
      mechanisms and activation of fibrinolysis. Experimental chronic prostatitis in
      rats induced hemostatic shifts to hypercoagulation. These parameters returned to
      normal after 5- and 10-day course of prostatilen administration. A single
      prostatilen dose was unable to produce the above action. As to patients with
      chronic prostatitis, there were also prostatilen-induced platelet-vascular
      hemostatic normalization and fibrinolysis activation. Hemocoagulation was
      affected in a less degree. Prostatilen effects were unrelated to the disease
      stage. Normalization of hemostasis seems to be one of the factors of prostatilen
      therapeutic efficacy in chronic prostatitis. This peptide is found effective as a
      pathogenetic treatment of chronic prostatitis.

PMID- 9245058
TI  - [The treatment of distal hypospadias in children].
AB  - The authors propose a new treatment of distal hypospadia without distortion of
      the penis. From 1990 to 1994 the operation was performed in 193 boys aged from 4
      months to 14 years. The new procedure was tried in 67 patients. It consists in
      dissection of the skin flap along the ventral surface of the penis with a special
      cut on the glans penis. The proximal part of the flap is isolated and placed on
      the glans penis. The urethra is formed on the urethral catheter using interrupted
      inverting subcuticular sutures (prolen 6/0). The urethra is covered with the
      preputial skin transformed from the dorsal penis. The edges of the dissected
      glans penis are sutured with cutaneous preputial flap in the frenulum region to
      increase the urethral diameter in the distal part. The 6-48-month follow-up
      results are good: postoperative complications occurred in 7.4% of cases instead
      of 15.5%: urethral fistulas and postoperative wound opening were registered in 3
      and 2 patients, respectively. Reoperations were successful. Cosmetic and
      urodynamic results were good. The above method of urethral reconstruction is a
      method of choice in the treatment of distal hypospadia.

PMID- 9245059
TI  - [Fluctuations in the maximal intraurethral pressure and urination disorders in
      women].

PMID- 9245060
TI  - [The use of Casodex (bicalutamide) in the treatment of disseminated prostatic
      cancer].

PMID- 9245061
TI  - [Hyperbaric oxygenation in uronephrology].

PMID- 9245062
TI  - [Information on the International Symposium on Prostatic Cancer].

PMID- 9245063
TI  - [The rapid microbiological control of the efficacy of the antibacterial therapy
      of bacteremia and septicemia].
AB  - No previous isolation of the agent on the media is needed in using a new
      microbiological express-method of automatic control over antibacterial therapy of
      bacteremia and septicemia. The method is efficient in determination of
      sensitivity to the drug of the whole heterogeneous population of bacteria. It
      does not predict efficacy of antibacterial therapy but states the presence or
      absence of the effect in vivo. The method is integral, evaluates antibacterial
      plasma titer suggesting adequate correction. The duration of the test is maximum
      12 h that is 3-4 times less than other methods.

PMID- 9245064
TI  - [Successful gamma globulin therapy in a patient with anti-IgA antibodies].
AB  - A case report of a patient suffering from common variable immunodeficiency with
      anti-IgA antibodies is described. These antibodies were probably the cause of
      repeated anaphylactic reactions during substitution gammaglobulin treatment, and
      lead to discontinuation the therapy lasting 4 years. The reintroduction the
      therapy was enabled by the therapy with low-IgA contents intravenous
      immunoglobulin (Endobulin, Immuno Vienna).

PMID- 9245065
TI  - [Acute and chronic heart failure].
AB  - Cardiac failure is a syndrome which comprises ventricular dysfunction (confirmed
      by echocardiography) and compensating mechanisms (immediate activation of the
      sympathetic nerve and functioning of Starling's mechanism, within hours or days
      activation of RAAS within days or weeks hypertrophy of the heart). Cardiac
      failure develops rapidly either in a previously healthy subject (first extensive
      IM, diffuse myocarditis, acute aortic or mitral regurgitation) or in a damaged
      heart (IHD, KMP, defect) as a result of sudden excessive burdening (ischaemia,
      arrythmia, infection, surgery etc.) or spontaneously (end-stage). It is
      manifested above all by "backward" failure (pulmonary oedema). The pulmonary
      pressure must be rapidly reduced: i.v. nitrovasodilators act immediately, i.v.
      furosemide acts within 10-15 min. (in can, however, reduce the circulating volume
      which has not increased during the first failure). Also O2, anodynes. In the
      subacute stage (without any precise time limits) which may develop in serious
      cases from acute failure, or develop as a result of deterioration of chronic
      failure, in addition to congestion, symptoms caused by "forward" failure are in
      the foreground. These are symptoms caused by a reduced minute output and
      hyperfusion of tissue. It is indicated to administer substances which improve
      work tolerance, i.e. positive inotropics (digitalis, beta-agonist or
      phosphodiesterase inhibitors). If the blood pressure drops, a combination of
      dopamine and dobutamine should be administered; if the respiratory volume drops,
      artificial pulmonary ventilation, in case of persisting oedema continuous
      arteriovenous haemofiltration, in severe failure intraaorrtic balloon
      contrapulsation etc. In an irreversible state urgent or elective orthoptic
      transplantation of the heart should be considered. In chronic heart failure an
      important component of comprehensive treatment is in addition to treatment of
      congestion and hypoperfusion, prevention of "cardiovascular remodelling" by means
      of angiotensin convertase inhibitors etc. Which improve the quality of life and
      survival. Arrhythmias are an independent prognostic factor.

PMID- 9245066
TI  - [Infection with Helicobacter pylori and its serologic detection].
AB  - Pathogenicity of Helicobacter pylori is based partially on the production of
      toxic substances. On the other hand the gastric mucosal injury may be caused by
      the Helicobacter pylori-induced host inflammatory response. Considerable antibody
      response during Helicobacter pylori infection provides a ground for indirect non
      invasive serological detection. Appropriate clinical applications of serological
      tests are based on a good understanding of the antibody response characteristics
      during Helicobacter pylori infection.

PMID- 9245067
TI  - [Antigens in the serologic detection of Helicobacter pylori infection].
AB  - The paper deals with the types of antigens for detection of anti-Helicobacter
      pylori antibodies. There are informations about the protein composition of
      Helicobacter pylori and about the specificity and immunogenicity of particular
      proteins. The authors review and evaluate different types of antigenic
      preparations used in serological tests and inform about the commercial kits for
      serological detection of Helicobacter pylori infection.

PMID- 9245068
TI  - [Leptin and its biological and clinical significance. Is leptin and insulin
      resistance in the X-5H hormonal metabolic syndrome a parallel or causally-linked
      phenomenon?].
AB  - Leptin 167 an amino acid product of the recently discovered obesity gene "ob
      gene", is a tissue hormone of adipose tissue. It is a hormonal satiety signal or
      a signal for terminating food intake. Its level rise after a meal or after
      administration. Rats with a mutation of the ob-gene have zero or very low leptin
      levels, are hyperphagic, obese and sterile, develop diabetes as a result of
      overeating. Administration of recombinant leptin arrests hyperphagia, the body
      weight declines and sexual function improve partly, in particular in males. It
      seems that leptin controls not only the function of the hypothalamic satiety
      centre but also the output of GnRh and other liberins as well as
      thermoregulation, muscular and sexual activity and thus energy expenditure. In
      the majority of obese rats and human the leptin levels are significantly higher
      compared with asthenic individuals, proportionate to the percentage of body fat
      and BMI. Obesity promotes also insulin resistance and penetration of the H
      phenomenon into the phenotype. In the insulin resistance syndrome (5H-X) it may
      thus be assumed that there is a parallel leptin and insulin resistance, probably
      of the postreceptor type, and even a causal association, as the "db" gene is
      identical with the gene for leptin receptors.

PMID- 9245069
TI  - [Rheumatology and rheumatologists today].

PMID- 9245070
TI  - [Pharmacotherapy in patients after myocardial revascularization surgery 1991
      1995].
AB  - The authors discuss in a retrospective study pharmacotherapy administered to 302
      patients after revascularization surgery of the heart muscle in 1991-1995 in
      Konstantinovy Lazne. In the introduction they evaluated the ratio of drugs used
      in secondary prevention of infarctions incl. trends of their use in individual
      years between 1991-1995 (antiaggregation treatment-beta-blocking agents, calcium
      channel blockers, ACE inhibitors, hypolipidaemic agent, rapidly acting and
      retardes forms of nitrates). They evaluate specially medication with beta
      blocking agents from the aspect of cardioselectivity, internal sympathomimetic
      activity, membrane stabilizing effect and period of action. When evaluating
      pharmacotherapy they found a satisfactory state of affairs as regards
      administration of antiaggregants and beta-blocking agents. They found reserves as
      regards the use of ACE inhibitors and hypolipidaemic agents in indicated
      patients. A relatively high percentage (20%) of patients with angina pectoris
      persisting after surgery did not take rapidly acting nitrates.

PMID- 9245071
TI  - [Estimation of the mean right atrial pressure using echocardiography].
AB  - The authors measured in a group of 30 patients invasively the pressure in the
      right atrium and at the same time or within 60 minutes the diameter of the
      interior vena cava and its changes in conjunction with respiration. They revealed
      a statistically significant relationship between all parameters of the diameter
      of the interior vena cava assessed by echocardiography and the mean right atrial
      pressure. The closest correlation was found in the index of the inspiration
      diameter of the inferior vena cava (p = 0.01; r = 0.824). A critical value of the
      index of the inspiration diameter of the inferior vena cava greater than or equal
      to 10 mm revealed patients with a pathologically elevated pressure in the right
      atrium with a 100% sensitivity and 88.9% specificity. Measurement of the diameter
      of the inferior vena cava and its respiratory variations is a suitable method for
      estimation of the mean right atrial pressure.

PMID- 9245073
TI  - [Fibrinogen and diabetic microangiopathy].
AB  - Diabetic microangiopathy is in its developed form a serious complication for
      patients with diabetes, in particular diabetes type 1. An important aspect of
      prevention of organ damage is early assessment of factors which accelerate the
      development of microangiopathy. In the submitted paper the authors draw attention
      assessment of plasma fibrinogen, thrombocyte aggregation in relation to renal
      functions in type 1 diabetics as well as other indicators which promote the
      development and acceleration of diabetic nephropathy. In patients with diabetic
      nephropathy a correlation was found between fibrinogen and thrombocyte
      aggregation as well as between the rate of urinary albumin excretion, systolic
      and median blood pressure which are risk factors which increase the mortality of
      patients with type 1 diabetes.

PMID- 9245072
TI  - [The role of calcium inhibitors in the treatment of arterial hypertension].
AB  - Base on their own experience with isradipine and results of a multicentric study
      with amplodipine in the Slovak Republic, as well as based on data in the
      literature the authors conclude that: 1. In the treatment of arterial
      hypertension associated in the syndrome of insulin resistance (syndrome X and 5H
      resp.) with type 2 diabetes, hyperlipiproteinaemia and hyperinsulinism drugs of
      first choice include ACE-inhibitors and Ca antagonist of the second generation,
      dihydropiridine type, such as amplodipine, isradipine, fellodipine, nirtendipine
      etc. ACE inhibitors and Ca antagonist of the dihydropyridine type with prolonged
      effect have a good tolerance, few undesirable effect, a favourable effect on the
      decline of BP, regression of hypertrophy of the left ventricle and vascular wall;
      they do not cause deterioration of insulin resistance and thus do not interfere
      with compensation of diabetes and associated hyperlipoproteinaemia. 2. ACE
      inhibitors moreover reduce glomerular filtration and albuminuria and thus retard
      along with the effect on BP the progression of diabetic nephropathy. 3. In pre
      existing hyporeninemic hypoaldosteronism (cca in 18% diabetic subjects) they can
      however cause dangerous hyperkalinaemia by further inhibition of the damaged
      renin-angiotensin-aldosterone system. In instances Ca inhibitors are indicated.
      The latter activate RAAS and do not have an impact on albuminuria. By their
      effect on the vas deferens they can increase glomerular filtration. 4. Diuretics
      are not suitable for the treatment of hypertension in X syndrome and the use of
      beta-blocking agents even with ISA and beta-1-selective preparations in
      restricted in particular when insulin is administered or other numerous
      contraindications are present (cardiac failure, bradyarrythmias, bronchitis
      etc.). Perhaps a combination of ACE-inhibitors and Ca antagonists of the 2nd
      generation with an alpha-blocking agent or hybrid alpha-beta-blocking agent is a
      suitable solution.

PMID- 9245074
TI  - [Occurrence of copper metabolism abnormalities in the families of four
      individuals with newly diagnosed Wilson's disease].
AB  - The author describes the incidence of abnormalities of copper metabolism in
      families of four patients with recently diagnosed Wilson's disease. The patients
      were three men ad one girl, age 17-22 years where Wilson's disease was diagnosed
      on the basis of liver symptomatology and a typical laboratory finding. The period
      which elapsed between detection of the first clinical and laboratory symptoms and
      the establishment of the diagnosis of Wilson's disease varied between 1 months to
      eight years. Clinical and laboratory examination of all relatives of the affected
      subjects (parents and siblings) revealed an increased incidence of biochemical
      abnormalities as regards copper and ceruloplazmin levels in siblings. In the
      parents of the affected patients there were no marked biochemical abnormalities
      in the laboratory results in the examined families. Among seven siblings of the
      affected subjects in three Wilson's disease was diagnosed and in one instance a
      reduced serum copper and ceruloplazmin level without signs of increased copper
      retention in the organism. In one family Wilson's disease was detected in three
      siblings. The assembled findings confirm the urgency of systematic and careful
      laboratory and clinical examination of siblings of subject with diagnosed
      Wilson's disease.

PMID- 9245076
TI  - [Immunoscintigraphy examination of bone marrow in patients with hematologic
      diseases].
AB  - In 36 patients with different haematological diseases the authors examined by
      immunoscintigraphy the bone marrow using the 99mTc preparation Scintimun
      Granulozyt of Behring Co. They studied the distribution of haematopoietic tissue
      order to detect deviations from normal, focal defects, elongation of
      haematopoiesis into the periphery of long bones or extramedullary haematopoiesis.
      Distribution of haematopoietic tissue was evaluated visually and
      semiquantitatively.

PMID- 9245075
TI  - [Relation between types of erythrocyte membrane defects and the clinical picture
      in hereditary spherocytosis].
AB  - From total number of 130 patients with hereditary spherocytosis from 75 families
      in 119 patients from 69 families a defect of membrane proteins was detected. In
      23 families (33.3%) a spectrin defect was involved, in 32 families (46.3%) a
      combined defect of spectrin and ancyrine and in 14 families (20.3%) a defect of
      band 3 proteins. Investigation of the membrane defect and the clinical and
      laboratory picture revealed that the band 3 protein defect of spectrin and
      ancyrine. There are significant differences in the clinical picture of the two
      latter defects.

PMID- 9245077
TI  - [Use of PTCA in a gastroepiploic aortocoronary graft].
AB  - The use of the gastroepiploic inferior artery as an aortocoronary graft is at
      present a method of third choice after the mammary artery and venous grafts in
      revascularizations of the heart muscle. The results are comparable with those
      obtained with the mammary artery. With regard to the increasing number of
      operations are more plentiful on the development of atherosclerosis of the above
      mentioned graft. This dumps the initial enthusiasm that in this artery
      atherosclerosis does not develop. Reports on PTCA, when this artery is affected,
      are so far rate. The authors performed a successful PTCA of this graft in a
      patient with complete affection of the coronary circulation where alternative
      possibilities of revascularization of the heart muscle were practically
      exhausted. To improve the technique a suitable type of catheter must be developed
      which will make it possible to overcome technical problems associated with
      cannulation of artery and its dilatation.

PMID- 9245078
TI  - [Catecholestrogens: synthesis, properties and role in carcinogenesis].

PMID- 9245079
TI  - [Epidemiology of malignant skin neoplasms in Russia].

PMID- 9245080
TI  - [Clinical immunogenetics of stomach cancer in Western Siberia].
AB  - An immunogenetic examination of 86 cases of stomach cancer established a
      correlation between predisposition and resistance, on the one hand, and the
      distribution of allele sets of HLA-genes (classes I and II), on the other. The
      relationship was found to vary according to sex and age. The most significant
      relationships with respect to predisposition were identified for HLA-B51 (RR =
      19.82) alleles and allele combinations of HLA-DRI-DR7 (RR = 25.52) and HLA-A9-DRI
      (RR = 33.67). High relative risk of stomach cancer was attributed to the absence
      of relevant alleles in 91 patients included into the group of comparison. Also,
      combinations of allele sets were identified in healthy subjects which never occur
      in stomach cancer patients. The results provide a substantiation for developing
      an automated system of interpreting HLA-typing data which are instrumental in
      evaluating the patient's predisposition, resistance and prognosis.

PMID- 9245081
TI  - [Correction of trace element metabolism in patients with breast cancer during
      radiation therapy].
AB  - Certain mechanisms of pathogenesis of response to radiation and procedures for
      aborting them have been investigated. The study included 162 patients with breast
      tumors receiving radiation therapy. A new method of correcting radiation response
      was developed on the basis of evidence pointing to a radiation-induced shift in
      trace element levels toward heavy metal accumulation. The latter was effectively
      corrected and radiation damage was decreased due to the use of 33% solution of
      dimexide and the trilon B metal complex. It is suggested that radiation-induced
      changes in trace elements levels be studied as an indicator of response to
      treatment and its effectiveness in cancer patients.

PMID- 9245082
TI  - [Clinical experience of bone marrow scintigraphy in cancer patients].
AB  - 129 patients with various malignant tumors and 10 persons from the control group
      were examined by BM scintigraphy with radio-colloids. The following scintigraphic
      signs were associated with neoplastic bone marrow pathology: 32 patients with BM
      metastasis had focal or multifocal defects on BM scans, 8-localized areas of
      increased tracer accumulation ("hot spots"), 5-diffusely diminished tracer
      uptake. There were no correlations between survival and grade of peripheral
      expansion of tracer uptake (scintigraphic sign of hematopoietic peripheral
      expansion) and the probability of bone marrow BM involvement by tumor cells.

PMID- 9245083
TI  - [Effectiveness of various chemotherapy regimens for patients with chronic myeloid
      leukemia in blast crisis].
AB  - The evidence on the treatment of 146 cases of blastic (myeloid-101, lymphoblastic
      45) crisis (BC) have been analyzed to evaluate the efficacy of different schemes
      of polychemotherapy (PCT) administered for blastic crisis myeloid leukemia (CML).
      The study of the 7 + 3, 7 + 3 + B. RP, VRP, RAP, VAP, CROMP. COP + Rub schemes as
      well as large doses of cytosar showed the 7 + 3 and RAP to be the most effective
      for myeloid BC and COP + Rub and VAP-for lymphoblastic one. Complete clinico
      hematologic remission was 55 and 56%, respectively, in myeloid BC and 50 and 57%,
      respectively, in lymphoblastic BC. Relatively lower antitumor effect was recorded
      for the CROMP and RP in myeloid and the VRP in lymphoblastic crisis. Actuarial
      survival was assessed both for the entire CML group and each type of crisis and
      PCT scheme, and it was shown that more cases of lymphoblastic BC survived while
      fewer of them survive 3-5 years. However, 6-year survival rates were identical in
      both groups. Survival in the 7 + 3 group appeared to be higher than that in the
      VRP group suffering from lymphoblastic. BC. To summarize, the 7 + 3 and RAP
      schemes proved the most effective treatment for myeloid BC, while the COP + Rub
      and VAP for lymphoblastic BC.

PMID- 9245084
TI  - [Effect of patients' gender on the course of chronic myeloid leukemia].
AB  - Chronic myeloid leukemia course was evaluated versus sex in 271 patients. Chronic
      stage involved more pronounced leukocytosis, thrombocytosis and splenomegaly in
      females, the latter showing higher susceptibility to anemia. As a result,
      treatment has to deal with a greater mass of tumor. A relatively longer survival
      time in males (44 and 42 months, respectively) suggest a higher effectiveness of
      therapy in such patients. When diagnosed, leukocytosis, thrombocytosis, enhanced
      splenomegaly and anemia should be regarded as factors of unfavorable prognosis.

PMID- 9245085
TI  - [A method of fluorescence spectral analysis of lymphocyte function in cancer
      patients].
AB  - A luminescence microspectral examination of lymphocytes in peripheral blood
      sampled from ovarian tumor patients has shown spectral pattern, and,
      particularly, parameter alpha (ratio of one-spiral to two-spiral nucleic acids in
      cell) and parameter alpha distribution pattern to vary in the course of
      treatment: as efficacy increases, the lymphocyte fluorescence spectrum shows two
      peaks (lambda = 530 and 640 nm) of nearly identical intensity, parameter alpha
      grows, too, and its distribution shifts to the right. This mirrors an activation
      of synthetic and functional processes going on in peripheral blood lymphocytes of
      patients and points to enhanced non-specific resistance.

PMID- 9245086
TI  - [Classification of pesticides according to carcinogenicity to man].
AB  - A classification of pesticides according to their carcinogenic hazard is
      presented. It is part of a more comprehensive classification of toxic, mutagenic
      and other pesticides. All the agents are divided into four classes: extremely
      hazardous, hazardous, moderately hazardous and slightly hazardous. Class I
      corresponds to Group 1 of the classification of the International Agency for
      Research on Cancer (IARC)-the agent confirmed as hazardous to humans. Class 2
      (hazardous agents) is subdivided into three subclasses (2A, 2B and 2C) to ensure
      a more differentiated approach to evaluation of pesticides; the corresponding
      group of the classification is divided into two groups. Like group 3 of the IARC
      classification, class 3 (moderately hazardous agents) covers substances with
      limited evidence of carcinogenicity to animals. Unlike the IARC classification,
      it does not include unclassifiable agents which are not subject to consideration
      when pesticides are submitted for registration. Another distinction from the IARC
      group 3 is the inclusion of agents on sufficient evidence of their
      carcinogenicity but obtained with maximum tolerated dose only. Regulatory actions
      to be taken depending upon the class of hazard are discussed.

PMID- 9245087
TI  - [The effect of the murine stromal cell line MS-5 on the proliferation and
      apoptosis of human erythromyeloid leukemic cell line K562].
AB  - Effects of stromal environment on human leukemic cell apoptosis and proliferation
      have been investigated. The MS-5 cell line (kindly provided by Dr.Itoh) capable
      of supporting human hemopoietic cells and the K562 human erythromyeloid leukemic
      cell line were used. The total increment of cultured leukemic cells was lower
      than in control due to their co-cultivation with stromal cells, 96% of cells
      remaining viable. Colony formation by K562 cells appeared to be significantly
      lower, too (7.2 vs. 22 colonies per 10(3) cells). Inhibition by stromal cells was
      reproduced when stromal and leukemic cells were separated by a 0.5% agar layer as
      well as when leukemic cells were cultured on an agar layer which contained a 50%
      condition medium. Morphological signs of apoptosis in 78.75 +/- 7.64% of leukemic
      cells, as a result of serum deprivation, were in evidence after 72 hr. while only
      14.33 +/- 3.69% of cells co-cultured with MS-5 died. Only 4% of adherent cells
      showed morphological signs of programmed death. Since protein bcl-2 was not
      detected in K562 cells it may be suggested that apoptosis of leukemic cells co
      cultured with stromal ones does not use the bcl-2 gene pathway. Stromal cell
      mediated inhibition of proliferation may be effected through humoral mechanisms.

PMID- 9245088
TI  - [Inhibitory effect of the radiosensitizer AK-2123 on experimental liver
      metastasis and active transport of calcium ions].
AB  - Radiosensitizer AK-2123, a triazol, has been shown to significantly inhibit the
      development of hepatic metastases induced in syngeneic mice by intrasplenic
      injections with cels of bowel adenocarcinoma. The antimetastatic effect was
      produced by use of a very low dose of the drug. A therapeutic dose of AK-2123 has
      been shown to inhibit active transport of calcium ions across sarcoplasmic
      reticular cells effected by Ca(2+)-dependent Mg(2+)-activated ATPase. It is
      suggested that the antimetastatic effect of AK-2123 is determined by at least
      partial inhibition of active transport of calcium.

PMID- 9245090
TI  - [Experimental study of the antitumor properties of acetomepregenol].
AB  - Antitumor effect on hormone dependent tumors has been demonstrated following oral
      and parenteral treatment of mice and rats with a gestagenic drug --
      acetomepregenol.

PMID- 9245089
TI  - [Modulation of the antitumor effect of cyclophosphamide by the recombinant
      probiotic Subalin].
AB  - A new preparation "subalin" developed on the basis of a recombinant saprophyte
      strain of Bacillus subtilis 2135/105 producing human interferon alpha-2 has been
      tested for its ability of increasing the effectiveness of antitumor therapy. The
      study used Lewis lung carcinoma bearing mice C57B1/6 treated with injections of
      60 mg/kg body cyclophosphamide, intraperitoneally, on days 3 and 7 of tumor
      growth. Subalin was administered per as on days 1-14 after tumor transplantation.
      Combined treatment with cyclophosphamide and subalin resulted in a significantly
      higher inhibition of primary tumor growth and metastatic spreading as compared
      with control receiving cyclophosphamide alone. Also, there were fewer animals
      with metastasis; the average number of these lesions per animal and the total
      affected area were less. Subalin proved to exert a moderate antitumor and
      antimetastatic effect. The cytostatic activity of peritoneal macrophages was
      higher in mice treated with subalin. It is suggested that the chemo-sensitizing
      and antitumor effects of subalin are due to its ability to induce endogenous
      interferon production.

PMID- 9245091
TI  - [The effect of prenatal diethylstilbestrol treatment on 1,2-dimethylhydrazine
      induced carcinogenesis in C3HA female mice].
AB  - C3HA female mice received 0.1-0.3 mg/g body weight diethylstilbestrol (DES) on
      day 17 of gestation. Their descendants received a total of 20 injections of 1.2
      dimethylhydrazine (DMH), subcutaneously, weekly, starting from month 2. Prenatal
      DES significantly inhibited the development of DMH-induced clitoral gland tumors,
      particularly, hemorrhagic ovarian cysts which were the frequent cause of death
      due to their rupture into the abdominal cavity. A significant decrease in cyst
      incidence resulted in higher survival in mice receiving combined therapy. The
      results were attributed to DES-induced hyperestrogenization which was confirmed
      by vaginal smears examination.

PMID- 9245092
TI  - [Current principles of surgical treatment for early colorectal neoplasms].
AB  - A distinct correlation between tumor process expansion within the large bowel
      wall and dissemination has been established thus suggesting a concept of early
      colorectal cancer. Indications for limited surgery for early large bowel cancers
      are discussed. Both local excision and standard radical surgery offer practically
      the same advantage in cases of carcinoma located within mucosa and the submucosal
      layer of the intestinal wall.

PMID- 9245093
TI  - [Inguinal lymphadenectomy in malignant anal tumors].
AB  - The evidence on the immediate and end-results of lymphadenectomy carried out in
      36 patients with malignant tumors of the anal canal is presented. It appears to
      be expeditious to opt, for inguinal lymphadenectomy (after Ducuing) in cases of
      involvement of the inguinal lymph nodes suffering from primary malignant tumors
      of the anal canal.

PMID- 9245094
TI  - [Ultrasonography and differential diagnosis of breast cancer].
AB  - The echographic features of different neoplasms of the breast were studied in 449
      patients. The most frequent-symptoms of carcinoma, fibroadenoma and cyst and
      their significance for differential diagnosis are discussed. A diagnostic
      procedure is suggested for use in ultrasonic examination of the breast.

PMID- 9245095
TI  - [Lymphatic cysts arising after extended surgery for cervical and endometrial
      tumors].
AB  - Retroperitoneal lymphatic cysts account for 10.0-15.0% of complications of
      extended hysterectomy for tumors of the cervix uteri and endometrium. The data on
      1,093 cases treated at the Institute Clinic in 1980-1994 have been analyzed to
      establish retroperitoneal lymphatic cyst frequency, factors of its development,
      criteria of diagnosis and procedures of therapy and prevention. Age over 50
      years, low differentiation of tumor cells, deep invasion and considerable local
      extent of tumor have been identified as factors of risk for lymphatic
      dissemination. Ultrasonic examination proved the most effective diagnostic
      procedure with a credibility of 85.5%. Depending on cyst size and condition of
      adjacent organs, treatment of postsurgical lymphatic cysts may be palliative or
      radical. In the present study, surgery was used in 28.8% of cases. Frequency of
      complications can be lowered by timely detection of early forms of cancer of the
      cervix uteri and endometrium which do not require lymphadenectomy.

PMID- 9245096
TI  - [Clinical experience with the use of Tantum Rosa in cancer patients].

PMID- 9245097
TI  - [Effect of various chemotherapy regimens on survival and cause of death in
      patients with multiple myeloma (retrospective study)].
AB  - A retrospective analysis of survival time and causes of death has been undertaken
      in 109 patients treated for multiple myeloma (MM) at the Hematologic Clinic of
      the Russian Research Institute of Hematology and Transfusiology in 1979-1995.
      Group I included cases of mono- and group II-polychemotherapy (PCT). Survival in
      patients with MM increased significantly (from 27 to 43 months) after PCT. The
      main causes of death in MM patients of group I were chronic renal failure and
      infectious complications, while in group II-intoxication syndrome including blood
      toxicity, toxic hepatitis, etc. In cases of this grave disease, the effectiveness
      of therapy appeared to depend on both main and supporting treatment. Of great
      importance was profuse hydration using diuretics, active rheologic preparations,
      plasmapheresis and other counter-complication means. Following the administration
      of immunity correction drugs (thymaline, tactivin, immunoglobulin), infectious
      complication incidence in group II dropped from 22 to 8.3%. It is suggested that
      the effectiveness of MM therapy is determined by stage-by-stage approach, course
      cycling of PCT and adequate evaluation of its criteria. PCT courses should be
      supplemented with infusion detoxication measures, particularly, in cases of
      highly aggressive PCT schemes, and procedures of immunity correction, hemo
      component therapy and plasmapheresis.

PMID- 9245098
TI  - [Early stages of prostate cancer].

PMID- 9245099
TI  - [The development of oncology service in Belorussia (the 80th birthday of
      N.N.Alexandrov)].

PMID- 9245100
TI  - [The influence of lead on neutrophils].
AB  - Defective function of the human neutrophils and disturbances in their metabolism
      in workers occupationally exposed to lead were presented. In vitro impairment of
      human neutrophil functions by lead were also described. The pathomechanisms of
      the observed changes were presented.

PMID- 9245101
TI  - [The effect of heavy metals on neutrophils].
AB  - The influences of some heavy metals i.e. of mercury, zinc, copper, manganese,
      nickel and cobalt on metabolic activity and functional states of human
      neutrophils were presented. Simultaneously the pathomechanisms of the observed
      disturbances were described.

PMID- 9245102
TI  - [A case of recurrent untreated non-hodgkin's lymphoma localized in the
      nasopharynx and maxillary sinuses after a 10-year remission].
AB  - We present the case of non-Hodgkin lymphoma (lymphoma malignum lymphocyticum)
      localised in nasal cavity and paranasal sinus (maxillary sinus). The patient
      suffered from weakness, fever and rhinorrhoea. We applied the chemotherapy (grade
      IV degrees) in COP, achieving partial remission. We also place emphasis on 10
      year period of idiopathic neoplasm remission since the establishment of
      diagnosis.

PMID- 9245103
TI  - [The role of prolonged cardiac pacing in management of secondary bradyarrhythmias
      based on personal experiences].
AB  - Three patients with bradyarrhythmia who were admitted to the Department for
      urgent pacemaker implantations are presented. The careful clinical evaluation
      revealed that these arrhythmias were remarkably secondary to underlying diseases
      (e.g. severe coronary heart disease, valvular defects). Surgical treatment
      applied in these cases (coronary bypass grafts, valve replacement) has resulted
      in successful outcome. We concluded that in some patients the pacemaker
      implantation alone, without heart surgery, would not be beneficial enough.

PMID- 9245104
TI  - [Massive hemorrhage from a gastric neuroma associated with a kidney neoplasm].
AB  - A case of a gastric neuroma and kidney cancer were reported. The first symptoms
      of the disease was gastric haemorrhage. Urgent endoscopy showed submucous tumor
      of the gastric wall. The physical examination showed a presence of a tumor of the
      rib, proved to be secondary deposit from kidney carcinoma which had been found on
      abdominal ultrasound examination. Submucous excision of the followed by left
      nephrectomy was performed. At present an intensive x-ray therapy of rib tumor is
      continued because of patient's disagreement for rib resection.

PMID- 9245105
TI  - [Symptomatic cytomegaly in a 6-month old infant].
AB  - The aim of our study is to present diagnostic and therapeutic problems in the
      case of 6-month old infant with cytomegaly infection. We observed typical
      symptoms of cytomegaly infection (central nervous system and liver damage,
      coagulopathy, anaemia) as well as electrolyte and serum lipid disturbances and
      urine densification abnormalities.

PMID- 9245106
TI  - [A case of large arachnoid cyst of the vertebral canal].
AB  - A case of initial diagnosis postinflammatory polyneuropathy with paraparesis
      inferior with sudden insufficiency of bladder sphincter during disease. The cause
      of disease was arachnoid cyst of vertebral canal.

PMID- 9245107
TI  - [Severe aplastic anemia as a complication of treatment with metizol].
AB  - Aplastic anemia is the rare hematologic complication of the antithyroid
      medication. We present here the case of 39-years old female who was treated with
      Thiamazole due to Graves disease. This and the others cases cited in the
      literature indicate that antithyroid drugs-induced aplastic anemia is
      characterised by severe clinical status and profound marrow hypoplasia or aplasia
      but good prognosis with short term recovering.

PMID- 9245108
TI  - [Tumor of a single functional kidney treated with selective embolization].
AB  - Occurrence malignant tumor in only one functional kidney (second one was small
      and cirrhotic with a large cyst) and potentiality of treatment with selective
      embolization of renal artery were cause of that report. Patient achieved a long
      and comfortable term of survival (without any troubles). We suggest that method
      is useful and safe for such cases.

PMID- 9245109
TI  - [Rheumatoid arthritis in a patient with osteopoikilosis].
AB  - 57-years old woman with spotted bones was reported, with concomitant rheumatoid
      arthritis. It was great concern because of low incidence of osteopoikilia and
      diagnosis obstacles concerning coexistence of this two pathologies.

PMID- 9245110
TI  - [Eighteenth century calendars as a source of Polish medical history].
AB  - The general decline of science which took place in the first half of the 18th
      century was a cause of a huge quantity of calendars editing. Calendars
      substituted for the former scientific literature. Up to 1763 over 800 calendars
      appeared. A half of them was published in Cracov. Those calendars differed from
      the contemporary ones. Apart from dates, they included not only basic information
      in history, geography agriculture economy but, not seldom, medicine as well. Most
      often they were written by university professors with a few physicians among
      them. Obviously, the level of the presented medical knowledge was very low. There
      wenadductions to astrology, wizardry and Provinience. But some diagnoses and
      therapeutic advice being a kind of doctor's manual, useful to so-called domestic
      medicine are still worth of the attention. First of all, phytotherapy chapter
      based on the folk empiricism, was the most rational. Thought 18th century
      calendars did not have much in common with real medicine, they make an
      interesting source to search for history of the Polish medicine of the Saxon
      times.

PMID- 9245111
TI  - [Lipids and atherosclerosis].
AB  - Atherosclerosis is a degenerative pathology of blood vessels leading to coronary
      heart disease, myocardial infarction and stroke. The basic lesion of
      atherosclerosis is the fibrous plaque, which consists of lipids, smooth muscle
      cells, macrophages and connective tissue matrix. Data derived from experimental
      and clinical studies indicate the crucial role of elevated serum LDL-cholesterol
      concentration in the formation of atherosclerotic lesions. HDL removes
      cholesterol from the arterial wall, stimulates arterial prostacyclin synthesis,
      inhibits adhesion molecules expression, has antioxidant properties and protects
      against atherosclerosis. Lipoprotein (a) competes with plasminogen for its
      binding site, leading to reduced fibrinolysis and is an important link between
      thrombogenesis and atherosclerosis. The pathogenic role of lipids in
      atherogenesis is discussed.

PMID- 9245112
TI  - [Laboratory diagnosis of lipid imbalance].
AB  - Accurate diagnosis of hyperlipidaemia is necessary for the effective treatment.
      Measurements in serum or plasma obtained after an overnight fast of over 16 hours
      should include total cholesterol, triglycerides and HDL-cholesterol
      concentrations; LDL-cholesterol can be calculated using the Friedelwald's
      formula. Lipoprotein electrophoresis is used to define different phenotypes of
      hyperlipoproteinaemia according to the Fredrickson's classification. More
      sophisticated tests include apolipoprotein analysis, determination of Lp(a)
      concentration, activities of enzymes involved in lipid metabolism and genetic
      studies. Secondary causes of hyperlipidaemia, including liver, kidney, endocrine
      disorders should be excluded using the laboratory methods.

PMID- 9245113
TI  - [Secondary hyperlipoproteinemias].

PMID- 9245114
TI  - [Anti-atherosclerotic action of hypotensive drugs].
AB  - Hypertension is an important risk factor for the development of atherosclerosis.
      Traditional antihypertensive therapy is not fully effective in prevention of
      cardiovascular abnormalities of hypertension. Two classes of hypotensive drugs,
      calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors, reduce
      atherosclerosis in several experimental models in animals. Anti-atherosclerotic
      effects of calcium antagonists include attenuation of endothelial dysfunction,
      prevention of LDL modification, stimulation of LDL receptor activity, inhibition
      of superoxide radical generation and inhibition of vascular smooth muscle cells
      proliferation and migration. In large angiographic trials calcium antagonists
      reduced the development of new atherosclerotic plaques. ACE inhibitors also lead
      to the lower incidence of atherosclerosis in experimental animals. They inhibit
      migration and proliferation of vascular smooth muscle cells, reduce macrophage
      derived foam cell accumulation, preserve protective endothelium function, reduce
      LDL modification and increase fibrinolytic activity. It depends on reduced
      angiotensin II synthesis, increased concentration of kinins, substance P and
      angiotensin-(1-7), inhibition of leukotriene B4 formation and improvement of
      insulin action. In some studies they also reduce plasma lipids concentration,
      including lipoprotein (a). ACE inhibitors were found to be ineffective in
      prevention of restenosis after PTCA in human but data derived from large,
      multicenter trials indicate that they are effective in the secondary prevention
      of myocardial infarction.

PMID- 9245115
TI  - [Dosage of drugs in patients with kidney diseases].
AB  - There are several reasons, why dosing of drugs in renal patients must be of
      special concern of the treating doctor. These are the followings: 1. The kidneys
      are the main eliminating organ for many drugs. This is the reason, why the
      concentration of drugs in renal parenchyma may reach toxic levels and exert
      irreversible damage on different morphological structures of this organ. 2. Many
      drugs are a priori nephrotoxic. In the case, such drugs must be used in renal
      patients, very careful monitoring of renal function is mandatory in order to
      avoid serious adverse effects. 3. In patients with failing excretory renal
      function, and especially in patients on haemodialysis or peritoneal dialysis
      treatment, knowledge of altered pharmacodynamics and pharmacokinetics of drugs
      caused both by the uraemic state and renal replacement therapy, is indispensable.
      4. Dosing of drugs, in patients with impaired excretory renal function is
      dependent upon their distribution volume, metabolic half-time, extrarenal
      clearance, renal clearance by the residual renal parenchyma and target
      therapeutic level. 5. From the above said it follows, that drug dosing in
      patients, with renal failure must be based on thorough pathophysiological,
      clinical and pharmacological knowledge.

PMID- 9245116
TI  - [A probe using isotretinoin for treatment of poorly differentiated leukemia].
AB  - Isotretinoin (Roaccutane) was used in a patient with low differentiated cell
      leukemia. Poor general condition, very low blood cell count as well patient's
      lack of consent made chemotherapy impossible. The effect of isotretinoin
      treatment was full hematological and clinical remission. The general patient's
      condition did not require additional medication.

PMID- 9245117
TI  - [Difficulties with diagnosing Wegener's granulomatosis].
AB  - The authors presents 14 cases Wegener's granulomatosis diagnosed in ORL Clinic in
      Warsaw. Localisation of the disease, clinical manifestation and difficulties of
      histopathological examination was described, emphasizing the role of ANCA test
      (antineutrophil-cytoplasm antibodies).

PMID- 9245118
TI  - [65th birthday of Professor Karl Bilek].

PMID- 9245119
TI  - [Immunohistochemical evidence of immuno-reactive hCG in the secretory endometrium
      in women].
AB  - The endometrium is a highly differentiated hormone dependent tissue. Its function
      is to make an implantation and pregnancy possible. The present study was carried
      out to investigate whether human endometrial cells are able to produce immune
      reactivity like hCG (ir-hCG). Immunohistochemical examinations of the endometrium
      were performed in 15 patients in the proliferative phase, 2 patients in the peri
      ovulatory phase and 13 patients in the secretory phase. Immunohistochemical
      investigations of placenta from women who had an artificial abortion were used as
      controls. No immunohistochemical reaction in the endometrium could be recognized
      during the proliferative phase. In contrast a clear reaction was observed in the
      cells of the epithelium of the endometrium during the secretory phase. At the
      beginning of the secretory phase the ir-hCG was detected to be in the basal
      subnuclear region. In the middle of the secretory phase ir-hCG was found in the
      apical supranuclear region and later on in the glands. In the stroma of the
      endometrium single immunohistochemical positive cells could be seen. The function
      of the ir-hCG of the endometrium should be elucidated.

PMID- 9245120
TI  - [Risk assessment in ovarian hyperstimulation syndrome (OHS) using the machine
      learning system (Decision Master) in 155 in-vitro fertilisations and embryo
      transfer (IVF/ET) cycles with a long stimulation protocol].
AB  - In 155 selected IVF/ET cycles stimulated with the long protocol 25 cycles with
      severe OHS are included which turned up later on (purposely overrepresented). An
      inductive machine learning program is described both in informatics and medical
      essentials. It is tested whether there exists an algorithm for ruling out the
      above-mentioned complication in the follicular phase of the same cycle already.
      By cross validation 89% of the OHS could be predicted and proven by practical
      rules using hormone and ultrasound values to avoid similar events in ongoing or
      further cycles.

PMID- 9245121
TI  - [Multivariate analysis of the significance of vaginal bacterial colonization in
      the occurrence of a preterm birth with various risk parameters].
AB  - Using a discriminance analysis we investigated the interactions between
      parameters of the vaginal flora and subclinical infection regarding preterm
      birth. The prospective study includes 222 single pregnancies, 114 of them with
      preterm labour or premature rupture of the membranes (PROM). The analysis
      includes information of a vaginal/ cervical smear (total number of pathogenic
      germs, species and groups of pathogenic germs), vaginal pH, maternal white blood
      cell count (WBC), C-reactive protein (CRP) and temperature. A normal vaginal
      flora was found in only 19%. Pregnancies with preterm labour have a higher
      quantity of pathogenic germs, whereas there is no difference of the germ group
      distribution. Moreover, pregnancies with preterm labour and 2 or 3 pathogenic
      germs have a higher rate of preterm birth. The discriminance analysis shows that
      only the affiliation the risk group with preterm labour and the parameters CRP
      and WBC have a significant selectivity for consequent preterm birth, but not the
      parameters containing information of the vaginal flora. The same is valid for the
      group with preterm labour, where only the parameters PROM and WBC are able to
      select significantly for preterm birth.

PMID- 9245122
TI  - [Development of breast surgery including plastic-reconstructive surgery results
      of the Universitatsfrauenklinik Leipzig].
AB  - The previous retrospective analysis surveys the introduction and development of
      breast surgery between 1992 and 1996 where a total of 741 procedures have been
      performed at our department. Recently, these operations represent about 10% of
      all gynecological procedures including small and extended operations. The total
      of breast surgical procedures have increased fivefold within the early
      introduction period of two years. Surgery of the breast was performed because of
      cancer in 335 cases (45%). Breast preserving procedures such as "wide excision"
      or segment resection with axillary nodal dissection (level I and II)
      respectively, have advanced from initially 46% in 1993 to 52% at present. 36% of
      women undergoing modified radical mastectomy receive an immediate breast
      reconstruction. So far, severe intraoperative complications were not encountered.
      The rate of postoperative and early complications needing therapy including cases
      with reoperation for postoperative haematoma formation (0.6%) or cases with
      impaired wound healing (3.1%) is assessed to be minor.

PMID- 9245123
TI  - [Usefulness of vaginal pH measurements in the identification of potential preterm
      births].
AB  - Ascending infections of the female genital tract as a cause of preterm birth have
      become major importance regarding the prevention of preterm birth. Measurements
      of the vaginal pH value are able to verify a alkalinisation of the vagina caused
      by a atypical vaginal flora. In a prospective study we measured the vaginal pH
      value using indicator paper and evaluated the results of a vaginal and cervical
      smear of 162 single pregnancies from 26 to 30 weeks of gestation. In contrast to
      normal pregnancies there is a relation between a pathological pH value > 4.5 and
      consequent preterm birth in pregnancies with preterm labour but also in
      pregnancies with other risk factors without symptoms of preterm labour.

PMID- 9245124
TI  - [From resuscitation space in the delivery room of the Women's hospital to the
      perinatal center of the Leipzig University].
AB  - Historical review on the development of neonatal intensive care and new-born
      nursing at the women hospital of Leipzig University from 1969 up to 1995 and the
      foundation of a Perinatal Center. The successes of perinatal care are
      demonstrated best by the decline of neonatal mortality of extremely low birth
      weight infants from more than 90% up to 20% in 1995. It is attributed to the
      progress in perinatal medicine as well as to a perfect functioning
      regionalization of high risk pregnancies.

PMID- 9245125
TI  - [From infant nurse to "baby-friendly hospital"--promotion of breast feeding in
      the University Women's Hospital in Leipzig].
AB  - The attitude of medical professionals towards natural infant feeding is decisive
      in the support of mothers who want to breastfeed. The atmosphere in a "Baby
      Friendly Hospital" is determined by the creation of conditions for breastfeeding
      on demand and for early, undisturbed mother-child contact. At the University
      Women's Hospital in Leipzig the development of good breastfeeding management was
      supported by the employment of a "breastfeeding nurse" and enhanced by continuing
      education for physicians, nurses and midwives in lactation and breastfeeding. In
      this way comprehensive, uniform information as well as practical guidance
      important for breastfeeding success were ensured for pregnant and young mothers.

PMID- 9245126
TI  - [Results of an individualized surgical therapy of vulvar carcinoma from 1973
      1993].
AB  - From 1973 through 1993, the University of Leipzig Women's Hospital treated 285
      patients with primary vulvar malignancies. Of these, 269 cases (94.3%) were
      squamous cell carcinomas. The patients age averaged 69 years (25-95 years). 232
      women (81.4%) were older than 60 years. Only 20 women (7%) were younger than 50
      years. During the given time period, 266 patients (93.3%) underwent primary
      surgery. Standard operative treatment, performed in 105 cases (39.5%), was
      radical vulvectomy and bilateral superficial inguinal lymph node dissection.
      Rather than en bloc resection (Butterfly method), separate incisions were used
      during node dissection. Only 3 patients (2.9%) experienced a relapse within the
      remaining skin bridge. Irradiation with a focal doses of ca. 50 Gy followed
      postoperative-adjuvant in those cases involving the inguinal lymph nodes. In
      contrast, 161 patients received largely individualized surgical treatment. Local
      tumor extension and patient age-dependent operability influenced the choice of
      treatment. Partial vulvectomy was performed in 37 cases (13.9%). Simple
      vulvectomy without inguinal node dissection was performed in 115 cases (43.2%)
      and 9 patients underwent vulvectomy with vaginal-, urethral- and partial
      sphincter resection, accompanied by myocutaneous flap transposition (M. gluteus
      maximus lobe). The cumulative (corrected) 5-year survival rate for all patients
      with squamous cell carcinoma was 68.6%. No significant relationship between
      patient age (> 60 years vs. < or = 60 years) and prognosis could be seen. Factors
      of importance to the prognosis, however, were primary tumor size (FIGO stage I
      vs. II vs. III/IV), principal tumor site (significantly poorer survival rates
      characterize both clitoral and multifocal carcinomas), histological staging (G1
      vs. G2/G3), inguinal lymph node involvement (pN+ vs. pN-) and degree of tumor
      resection in "healthy" (> or = 2 cm vs. < 2 cm). 5-year survival rates among
      those patients receiving individualized operative care did not differ
      significantly. Patient survival rates were 70.3% by partial vulvectomy, 78.2% by
      simple vulvectomy without inguinal node dissection and 67.6% by radical
      vulvectomy and bilateral inguinal node dissection with or without postoperative
      adjuvant irradiation. These findings, therefore, justify the individualized
      operative treatment of patients with vulvar carcinoma according to each patient's
      initial prognostic situation. The relatively seldom vulvar carcinoma should only
      be treated by experienced surgeons in an appropriate hospital environment.
      Moreover, assessment of histological sections must be standardized, reproducible
      and above all, include the very accurate evaluation of all resection edges.

PMID- 9245127
TI  - [Magnetically controlled immobilized systems in the microbiological monitoring of
      natural foci and environmental objects for the presence of the causative agents
      of dangerous infectious diseases].

PMID- 9245128
TI  - [Enteral clostridial infections caused by Clostridium perfringens type A (the
      pathogenic aspects)].

PMID- 9245129
TI  - [Phagovars of halophilic vibrios].
AB  - The results of the phage typing of 164 halophilic vibrios revealed the most
      frequent combinations of lysing monophages, denoted by numbers: 1 (A, B, C, D), 2
      (B, C, D), 3 (B, C) and 4 (C). In accordance with the proposed scheme, the phage
      typing of 398 cultures from different ecosystems was carried out. Phagovar was
      determined in 77.1% of the cultures. Most frequently occurred phagovars 1
      (31.9%), 4 (15.8%), 3 (6%), and 2 (3.7%). Their proportion was 61%. 11 other
      phage combination causing the lysis of the cultures constituted 16.1%; 22.9% of
      the cultures could not be types. The use of the proposed scheme of phage typing
      permitted the determination of the temporal, regional, ecosystemic features of
      the circulation of halophilic vibrios in different ecosystems and regions, which
      was important for epidemiological analysis.

PMID- 9245130
TI  - [The cholera threat in Rostov and preventive measures].

PMID- 9245131
TI  - [The role of Russian microbiologists in creating the theory of nonagglutinating
      vibrios].

PMID- 9245133
TI  - [A rapid method for assessing the virulence of Francisella tularensis in vitro].
AB  - A rapid and simple method for the in vitro evaluation of the virulence of F.
      tularensis is proposed. The optimal parameters--the concentrations of bacteria
      and the substrate (phenolphthalein phosphate), the time incubation in the serum-
      have been developed and special conditions for strains of different subspecies
      have been selected. The proposed method makes it possible to greatly reduce the
      time of obtaining results and to exclude labor-consuming experiments on
      laboratory animals when working with large collections of F. tularensis
      laboratory and natural wild strains. Moreover, the method widens the
      possibilities of experimenters in the evaluation of the effect of some mutation
      on the virulence of the strain under study.

PMID- 9245132
TI  - [A comparative study of Coxiella burnetii strains differing in virulence in the
      intratracheal infection of guinea pigs].
AB  - As found out in earlier investigations, after the intratracheal infection of
      guinea pigs with C. burnetii (the method of infection, most similar to aerogenic
      infection which is characteristic of Coxiella under natural conditions) the
      maximum amount of the infective agent is accumulated in the lungs of the animals,
      damaging the organs of the reticuloendothelial system. The present investigation
      has revealed that this method of infection makes it possible differentiate C.
      burnetii virulent strains, differing in the level of the accumulation of the
      infective agent in the lungs of guinea pigs.

PMID- 9245134
TI  - [A method for preventing experimental pneumococcal infection].
AB  - Lethal pneumococcal infection in mice, infected intranasally, can be induced only
      by highly virulent strains of pneumococci. The introduction of N
      acetylglucosamine and/or D-galactose, both 1 hour before the introduction of
      pneumococci or simultaneously with their introduction, prevented the development
      of this infection in 83-91% of mice used in the experiment. The use of the
      mixture of these carbohydrates did not change the level of their activity. These
      carbohydrates were shown to be capable of protecting mice from the intranasal
      introduction of 100-1000 LD50 of Streptococcus pneumoniae highly virulent
      strains, adapted to the respiratory tracts and lungs of mice.

PMID- 9245135
TI  - [The isolation and immunochemical characteristics of the basic iron-regulated
      protein in meningococci].
AB  - A sufficiently simple and easy method for the isolation of one of the basic
      meningococcal iron-regulated proteins (IRP), protein with a mol. wt. of 37 kD
      (IRP 37), was developed. To carry out fine chromatographic purification of this
      protein. Russian-made cation-exchange sorbents, synthesized on the basis of
      silica gels with chemically bound functional groups, were used. The use of such
      sorbents made it possible to isolate IRP in water-saline solutions. The study of
      the immunological properties of IRP 37 revealed that antibodies to IRP 37 were
      specific only to mouse and rabbit meningococcal antisera and were not detected in
      animal antisera to a number of other pathogenic and opportunistic bacteria. The
      study also revealed that antibodies to this protein were present in all examined
      sera of patients with meningococcal meningitis. The conclusion was made that IRP
      37 presented considerable interest for the immunodiagnostics and
      immunoprophylaxis of meningococcal and, probably, gonococcal infections.

PMID- 9245136
TI  - [New data on the specificity and genetic control of the capsular antigen (F1) in
      Yersinia pestis].
AB  - The specific features of the synthesis of antigenic fractions F1, obtained from
      the strains of different species of enterobacteria and their hybrids inheriting
      Y. pestis plasmid pYT, were determined at different cultivation temperatures and
      the preparations of these antigenic fractions were characterized. Preparations
      containing the diagnostic antigenic determinant F1 were obtained from
      disintegrated bacteria of Y. pestis plasmid-free strain and microbial cells of
      Klebsiella pneumoniae, Citrobacter freundii and Escherichia coli initial
      recipient cultures by Baker's method. These data were indicative of the
      chromosomal control of the synthesis of antigen F1, responsible for the
      manifestation of protective activity. The antigen synthesized in the absence of
      pYT was practically, not secreted on the cell-wall surface and could not be
      determined by tests made with the use of whole bacterial cells. The antigen thus
      detected did not possess the properties of the preparation of antigen F1,
      obtained from Y. pestis pYT-containing strain, though it was capable of inducing
      the formation of F1-specific antibodies.

PMID- 9245137
TI  - [The use of a method of estimating the count of viable Rickettsia prowazekii for
      the screening of efficacious antibiotics].
AB  - The possibility of the evaluation of antirickettsial activity of
      chemopreparations, both in vitro (by the inhibition of hemolytic activity) and in
      vivo (under the conditions of experimental pulmonary rickettsiosis in mice), with
      the use of the rapid method for the determination of the number of metabolically
      active rickettsiae is shown. The proposed approach may be used in the complex of
      mutually complementary methods for the screening of antirickettsial preparations.

PMID- 9245138
TI  - [An epidemiological investigation of a tularemia outbreak in Smolensk Province].
AB  - The investigation of the epidemic outbreak of tularemia morbidity among the
      population of Vyaz'ma, was carried out. In this investigation the disease was
      shown to be transmitted by the water route due to contamination of water in the
      local water mains as the result of serious violations of the rules of using water
      supply systems. In the process of the investigation of this outbreak a natural
      focus of tularemia, not registered heretofore, was discovered. The work
      emphasizes the inadmissibility of deviations from the generally accepted tactics
      of tularemia control, consisting of a complex of prophylactic measures, such as
      the vaccination of the population, deratization and disinfection, the examination
      of the foci of infection, state sanitary surveillance, especially with regard to
      the sources of water supply and the quality of water preparation, raising the
      level of professional skills of the personnel and sanitary education.

PMID- 9245140
TI  - [The characteristics of the protectiveness of a preparation of Vibrio cholerae
      outer membrane based on the data from a study using the ligated intestinal loop].
AB  - The study aimed at finding out the antiadhesive capacity of antigenic
      preparation, earlier obtained from V. cholerae outer membrane and highly
      effective with respect to cholera infection, was undertaken. The study was made
      on previously immunized adult rabbits who had been subjected to laparotomy under
      anesthesia and the ligation of intestinal loops, subsequently inoculated with the
      broth culture of V. cholerae eltor (P-3122, serovar Ogawa). The intestinal loops
      were studied histologically and bacteriologically with the calculation of the
      number of vibrios, the deduction of the adhesion index and the coefficient of the
      efficacy of immunization. The data thus obtained indicated that the specific
      immunization of rabbits with their subsequent inoculation with V. cholerae
      virulent strain suppressed the adhesive activity of the infective agent which was
      more pronounced in rabbits immunized with the preparation of V. cholerae outer
      membrane.

PMID- 9245139
TI  - [Zoonotic infections in the central and southern ulusy of the Republic of Sakha].
AB  - The serological survey of humans, as well as agricultural animals and rodents,
      for the presence of zoonotic infections, was carried out. Local inhabitants were
      shown to have contacts with the causative agents of pseudotuberculosis, enteric
      yersiniosis, tularemia, leptospirosis, Q fever, tick-borne rickettsiosis,
      chlamydiosis, toxoplasmosis. The immune stratum with respect to enteric
      yersiniosis was found to have a greater index, while the immune strata with
      respect to chlamydiosis, Q fever, pseudotuberculosis had the least indices.
      However, the indices of immune strata perceptibly varied in individual regions.
      The highest occurrence of antibodies to all above-mentioned zoonotic infections
      was registered in Megino-Kangalasskii, Amga and Neriungrinskii ulusy [correction
      of regions]. The probable sources of leptospirosis, toxoplasmosis and Q fever
      were agricultural animals, while the probable sources of enteric yersiniosis and
      leptospirosis were rodents.

PMID- 9245141
TI  - [The expression of Bordetella pertussis protective antigens during bacterial
      multiplication on a medium with a fixed chemical composition].
AB  - The possibility of obtaining native pertussis preparations with high
      immunobiological activity has been shown. To obtain such preparations, the use of
      B. pertussis selected strain, its growth under the conditions of static
      cultivation in a synthetic culture medium and the use of supernatants with the
      maximum content of protective antigens with the aim of obtaining protective
      complexes are necessary.

PMID- 9245142
TI  - [The quality and efficacy of a Russian live mumps vaccine].

PMID- 9245143
TI  - [The anti-influenza immunity of workers subjected to exposure to chemical
      substances].
AB  - The status of anti-influenza immunity in workers contacting with chemical
      substances having sensitizing properties was studied. Workers immunized with
      trivalent anti-influenza vaccine were found to have no expected increase in
      antibody titers. These findings were indicative of inadequate response and the
      impairment of nonspecific protection in the immunized workers. Such alterations
      of immune response make it necessary to carry out immunization with the control
      of immunological characteristics and the simultaneous administration of
      immunocorrective therapy.

PMID- 9245144
TI  - [The effect of immunomodulating doses of purified staphylococcal anatoxin on the
      spontaneous and mitogen-induced proliferation of mouse splenocytes].
AB  - Purified staphylococcal toxoid (PST) was shown to alter the spontaneous and
      mitogen-induced proliferation of mouse spleen cells. In vitro, PST inhibited
      spontaneous proliferation, as well as proliferation induced by the optimal dose
      of Con A (2 micrograms/ml) and the optimal and suboptimal doses of
      lipopolysaccharide (LPS) (100 and 50 micrograms/ml). At the same time the dose of
      1.5 binding units (BU) of PST, inhibiting spontaneous proliferation in vitro,
      induced strong proliferative response in combination with the suboptimal dose of
      Con A (1 microgram/ml). Our experiments demonstrated that the spontaneous
      proliferation of mouse spleen cells, immunized with the toxoid, remained
      unchanged (0, 15 or 15 BU/mouse) or increased (1.5 BU/mouse) the response of
      spleen cells of immune animals to ConA and LPS also changed in comparison with
      the control, depending on the conditions of the experiment. After the use of the
      combination of 2 micrograms of Con A and 1.5 BU of PST or 100 (50) micrograms of
      LPS and 1.5 BU of PST the inhibition of proliferative response was observed. The
      summation of the signals of the suboptimal dose of Con A (1 microgram) 1.5 BU of
      PST was demonstrated.

PMID- 9245145
TI  - [The role of Shigella dysenteriae toxin formation at different stages in the
      forming of the cellular immune response in experimental animals].
AB  - The immunomodulating action of genetically related pairs of strains of S.
      dysenteriae 1, differing by the presence of high molecular plasmid with a mol.
      wt. of 140 mD and transposon-mediated mutation in the tox-gene chromosome (4
      phenotypes: Inv+ Tox+; Inv+ Tox-; Inv- Tox+; Inv- Tox-), was studied. The study
      was carried out with the use of the experimental intraperitoneal infection of CBA
      mice with live Shigella cells in a dose of 5x10(7) microbial cells. For the first
      time the role of Shiga toxin synthesis at different stages of the formation of
      cell-mediated immune response was demonstrated in vivo. This response was
      manifested by the stimulation of hematopoiesis, pronounced sensitization of
      effectors of delayed hypersensitivity and an immunomodulating effect on
      immunocompetent B lymphocytes, synthesizing antibodies, specific to S.
      dysenteriae 1 LPS and non-specific to heterologous antigen (sheep red blood
      cells).

PMID- 9245146
TI  - [The pathomorphology and pathogenesis of glanders in laboratory animals].
AB  - The pathomorphology and cell-mediated response of the body to Burkholderia mallei
      in laboratory animals, highly sensitive and resistant to these bacteria. In the
      comparative study of the pathomorphology and pathogenesis of glanders in golden
      hamsters and white rats quantitative and qualitative differences in the
      histogenesis of response reaction and the morphology of immunocompetent organs
      were established. Cell-mediated reactions play a greater role in the limitation
      of the early spread of B. mallei in the host body than antigen-mediated
      mechanisms.

PMID- 9245147
TI  - [Apoptosis: the beginning of the future].

PMID- 9245148
TI  - [The hepatitis G virus].

PMID- 9245149
TI  - [The concept of an ecological approach to the therapy of intestinal infections].

PMID- 9245150
TI  - [The connection between respiratory disorders during sleep and peripheral
      autonomic insufficiency in diabetics].
AB  - To reveal the connection between sleep breathing disturbances (SBD) and autonomic
      insufficiency (AI) 23 patients with diabetes mellitus (DM) were examined (7 cases
      of insulin-dependent DM and 16 cases of noninsulin-dependent DM). Clinical
      examination, night polysomnography and autonomic nervous system assessment were
      performed. No connection between the existence and severity of AI and SBD was
      found in patients with DM of both types. Patients with more pronounced obesity
      had significantly higher number of SBD. The conclusion was made that SBD were not
      connected with AI in patients with DM, but obesity was an important factor in
      their genesis.

PMID- 9245152
TI  - [The clinical characteristics of endogenous mental diseases with paroxysm-like
      disorders].
AB  - Paroxysmal-like disorders (PLD) were observed in 11 patients with manic
      depressive psychosis and in 34 ones with shift-like progredient schizophrenia. 8
      variations of the fits were described by the author earlier and included the
      states from vegetative fits to complex psychotic ones with manifestations of
      Kandinsky-Clerambault syndrome. Clinical pattern of endogenous psychoses was
      characterized by considerable presence of affective disorders (both hypomanic and
      depressive), moreover depressive disturbances were observed more frequently.
      Debut of PLD was mentioned either before depressions' or in their structure: The
      appearance of psychotic symptoms in structure of affective phases does not change
      the character of paroxysmal-like states. It was supposed that endogenous diseases
      with PLD are the special variant of psychoses.

PMID- 9245151
TI  - [Circulatory encephalopathy in patients with arterial hypertension].
AB  - More accurate definition of the leading factors of development of discirculatory
      encephalopathy (DE) in patients with arterial hypertension was the aim of this
      investigation. The analysis of correlations between clinical and computer
      tomographical symptoms of DE on the one hand and the indices of central
      hemodynamics, head blood circulation and presence of atherosclerosis of head
      arteria on the other hand was performed. It was found that congestion in head
      venous system was the main factor in DE development. The conclusion was made that
      both atherosclerosis of head arteria and arterial hypertension promoted venous
      congestion in head by means of decreasing the amplitude of arterial pulsation and
      in turn the development of DE. Meanwhile, the increase of minute blood flow
      prevents it.

PMID- 9245153
TI  - [The psychopathological differentiation of pathological body sensations].
AB  - The special group termed as "somatic fantasies" (SF) was distinguished among
      pathological somatic sensations of heteronomous character. Psychopathological
      structure of SF differed from senestopathias in some signs: objectiveness--the
      sensation achieved the level of the real perception of physical phenomena and
      objects; formal-geometrical organisation--the possibility of their parametric
      estimation (in form, volume, size, etc.); space location--the clear correlation
      of feelings with certain organ or physiological process; dynamic characteristics-
      variability, mobility. The description of somatic sensations was characterized
      by allegory image as well as by metaphorical, affective saturation as compared
      with senestopathias. SF were observed in patients with borderline mental
      disorders in accordance with the 1CD-10 diagnostical headings: schizotypic
      disorder (F21), anxious phobic disorders (F40, F41), dissociative disturbances
      (F44), somatoform disorders (F45). 19 patients (6 males, 11 females; mean age
      32.6 years) formed the group examined. Two variations of SF were recognized which
      correlated with hysterical or schizotypic disorders of personality.

PMID- 9245154
TI  - [The treatment of demyelinating polyneuropathies of different origins with small
      doses of immunoglobulin G].
AB  - Application of small doses of IgG-Sandoglobulin (0.16 to 0.98 g per kg of body
      weight) was quite effective in 2 patients with Guillain-Barre syndrome and in 2
      cases of diphtheritic polyneuropathy. These patients had a severe form of the
      disease with disorders of essential functions. An international course of the
      disease in one case of IgG treatment was observed. Meanwhile preparation was
      uneffective in 2 patients with chronic inflammatory demyelinating polyneuropathy
      caused by lymphoproliferative process. It is worth while to accumulate experience
      to define optimal doses of the drug.

PMID- 9245156
TI  - [Free light-chain immunoglobulins in the biological fluids of patients with
      multiple sclerosis].
AB  - 15 patients with clinically significant multiple sclerosis (MS) were examined in
      terms of content of free light chains of immunoglobulins of kappa- and lambda
      types in blood serum, cerebrospinal liquor, lacrimal fluid, saliva, urine,
      indices were compared with corresponding data of 12 patients with other
      neurological diseases and of 10 healthy individuals (control group).
      Significantly increased content of kappa-chains in cerebrospinal, lacrimal fluids
      and urine was revealed in patients with MS as compared with other two groups and
      in saliva of patients as compared with controls. The frequency of alterations was
      high in all biological fluids of the patients with MS. Elevated content of kappa
      chains was most often observed in cerebrospinal fluid of the patients (13
      individuals). The changes observed reflected systemic activation of humoral
      immune response in MS. Examination of cerebrospinal fluid was most informative
      for differential diagnosis.

PMID- 9245155
TI  - [A comparative clinico-pharmacokinetic study of the use of equivalent daily doses
      of lithium carbonate and Contemnol].
AB  - Comparative study of the influence of equivalent doses of lithium carbonate and
      contemnol was studied in patients with phasic development of endogenous
      psychoses. 33 patients (17 men, 16 women) of 20-58 years or age were treated.
      According to IDC-10 there were observed schizoaffective psychoses in 22 patients
      (F25), bipolar affective disorders in 5 patients (F31) and chronic mood disorders
      in 5 individuals (F34). 2-daily comparative pharmacokinetic profiles of lithium
      carbonate and contemnol were presented and on the base of standard statistic
      analysis were estimated: lithium presence in blood, amplitude of variations of
      lithium concentration, number of peak concentrations, areas under pharmacokinetic
      curves. The study showed that concentration of lithium in blood increased
      gradually and achieved the maximal level in 6-7 hours after contemnol
      administration and was not practically changed during following 24 hours as
      compared to lithium carbonate. The results of the study confirmed that contemnol
      occurred to be the prolong of lithium carbonate and hadn't to be used more
      frequently than once a day.

PMID- 9245157
TI  - [Genetic predisposition factors for multiple sclerosis (based on the data from
      genotyping patients of the Russian ethnic group)].
AB  - Patients' genotyping of Russian ethnic group with multiple sclerosis (MS) was
      performed for the first time in two loci of the main complex of
      histocompatibility: in DR HLA class II (gene DRB1) and in the locus of tumor
      necrosis factors (TNF). There was no difference in the incidence of alleles
      groups which correlated with some specificity of DR. Meanwhile TNF-a1 and TNF-a9
      alleles were encountered significantly more frequently in patients and TNF-a7 in
      control group. When all the patients and controls examined were divided into
      groups in dependence on combination of DR and TNF it was found that relations
      observed between MS and TNF-a7 and TNF-a9 alleles were displayed much more in
      individuals which carried alleles of gene DRB1, corresponding to DR15
      specificity. These are alleles which are known as the main risk factor of MS in
      Caucasians. The patients with "protective" TNF-a7 allele were characterized by
      more favorable course of the disease. Thus highly significant genetic markers
      were revealed for the first time in region of TNF genes which were associated
      with increased or decreased risk of MS development at least in Russian ethnic
      group. There was also possibility of their interaction with group of DR15 alleles
      of DRB1 gene. One of the markers revealed (TNF-a7) occurred to be bound both with
      decreased risk of MS and with favorable clinical course, which was observed for
      genetic markers of MS for the first time. Manifestation of one or another
      property of TNF-a7 marker depends on the presence of alleles of DRB1 gene which
      corresponds to DR15 specificity.

PMID- 9245158
TI  - [Current general biological approaches to assessing psychopathies].

PMID- 9245159
TI  - [The brain of V. V. Maiakovskii].

PMID- 9245160
TI  - [An analysis of the trends and outlook for the development of neurogerontology].
AB  - Expert questioning was performed in accordance with special questionnaire of 42
      Ukrainian and 39 leading foreign gerontologists to reveal the tendencies and
      perspectives in the development of neurogerontology. The authors analyzed the
      opinion of the world scientists about the degree of the development and the
      significance of specific research trends, about the role of the separate forms of
      age-dependent pathology of central nervous system in structure of morbidity in
      the old age, about the role of NG in complex investigations concerning life
      prolongation, etc. Above-mentioned collective "portrait" of the modern NG
      permitted to ground more profoundly scientific priorities, planning and design of
      the studies in gerontology.

PMID- 9245161
TI  - [The prevalence of borderline mental disorders in persons of either sex].
AB  - Examination of patients in two Moscow general out-patient clinics (No 84 and 127)
      revealed that there were much more women (80.9%) with borderline mental disorders
      (BMD) in comparison with men. This finding corresponded well to literary data
      about higher incidence of BMD (especially of mild depressions) in women. However,
      profound investigation revealed that existing indices of BMD sex prevalence
      didn't reflect the real differences in BMD (affective especially) incidence in
      men and women, but they occurred most probably as the result of interaction of
      three factors, namely: the real sex difference in prevalence of these disorders,
      their masking by alcoholism in men, and differences in "medical behaviour" in
      women and men.

PMID- 9245162
TI  - [2 cases of anterior uveitis in multiple sclerosis patients].

PMID- 9245163
TI  - [The life and creative work of O. V. Kerbikov (on his 90th birthday)].

PMID- 9245164
TI  - [Current trends in the study of the pathogenesis of demyelinating diseases].

PMID- 9245165
TI  - [Cytokines in the immunopathogenesis of multiple sclerosis].

PMID- 9245166
TI  - [Neurotransmitter changes in multiple sclerosis].
AB  - Elevated levels of norepinephrine and of excitatory amino acids (glutamate,
      aspartate) were observed in cerebrospinal fluid of patients with multiple
      sclerosis while there were elevated content of glutamine, asparagine and glycine
      in their blood. An important point concerning these results was the relation
      between biochemical indices and the character of neurological symptoms, their
      severity as well as the course of the disease. The role of neurotransmitters in
      pathogenesis of multiple sclerosis and particularly in biochemical mechanisms of
      the relation between nervous and immune system that underlie the development of
      neurological deficiencies is suggested.

PMID- 9245167
TI  - Proceedings of the Vth Baltic Conference on Obstetrics and Gynecology. Malmo,
      Sweden, May 25-27, 1995.

PMID- 9245168
TI  - A longitudinal study of small-for-gestational-age births: prenatal risk factors,
      newborn characteristics and infant growth and development.

PMID- 9245169
TI  - Proceedings of the International Conference on Epithelial Hyperplastic Lesions of
      the Larynx. Ljubljana, Slovenia, October 28-30, 1996.

PMID- 9245170
TI  - [Kikuchi's disease. A rare cause of fever, lymphadenopathies and polyarthritis].
AB  - This is a case report of a 29-year-old white female patient with Kikuchi's
      disease, presenting fever, polyarthritis, lymph gland enlargement, anemia,
      leucopenia with a relative lymphocytosis, altered liver function tests and
      circulating immune complexes. A literature review is made with emphasis on the
      etiology, clinical course and pathogenesis of this illness.

PMID- 9245171
TI  - [The prevalence of hypertension in acromegaly].
AB  - AIM: To estimate the prevalence of hypertension (HT) in a group of patients with
      acromegaly at the moment of diagnosis and after treatment. PATIENTS AND METHODS:
      Fifty-seven patients, 43 females and 14 males with a mean age of 45.19 +/- 11.9
      years were studied retrospectively. In the last visit 9 patients (15.7%) were in
      remission and 47 (84.2%) had active acromegaly. We considered hypertensive the
      patients with systolic BP > or = 140 and/or diastolic BP > or = 90 mmHg.
      Hypertension was classified in four stages:- mild, moderate, severe and very
      severe. RESULTS: The prevalence of hypertension at the moment of diagnosis was
      35%. The hypertensive patients had a mean age of 51.75 +/- 9.3 years and
      normotensive patients 41.65 +/- 11.6 years (p < 0.001). In females the prevalence
      of HT was 27.9% and in males it was 57% (p = NS). In hypertensive patients (n =
      20), the mean BP was 159 +/- 15 (syst.)/97.2 +/- 9.8 (diast.), 16 patients (80%)
      had mild to moderate HT and the remainder had severe (n = 2) and very severe
      (n=1) HT. In the last visit, 22.2% of patients were cured and 46.8% of those with
      active acromegaly were hypertensive. None of the patients cured and initially
      normotensive developed HT; among those that were hypertensive (n = 3), 2 remained
      hypertensive and 1 became normotensive. Among patients with active acromegaly and
      initially normotensive, 7 developed HT 4.85 +/- 2.03 years later; of those
      hypertensive at diagnosis (n = 16), only one became normotensive. The last case
      was 27 years old. The patients that remained hypertensive had a mean age of 53.8
      +/- 6.85 years (41-62 years). CONCLUSIONS: The prevalence of hypertension at the
      moment of diagnosis was 35%, similar to the majority of studies published and
      higher than the general population. The hypertensive patients were significantly
      older the normotensive patients and most of them had mild to moderate HT. We
      observed an increase in the prevalence of HT over the years in the cases that
      maintained active acromegaly. In our series only one of the three patients cured
      became normotensive, therefore, we concluded that HT in acromegaly is frequently
      irreversible. The chances of normalization seems higher in younger patients and
      probably with a shorter duration of acromegaly.

PMID- 9245172
TI  - [Reconstruction of the anterior cranial base with a frontal muscle flap in
      cerebrospinal fluid fistulae].
AB  - Craniofacial infection is a major problem for the plastic and neurosurgical team.
      Previous successful experiences with free muscle and omentum flaps and the galea
      frontalis myofascial flap have been reported, avoiding disastrous complications
      after frontofacial advancements and the resection of skull base tumors. The
      authors report the clinical use of the galea frontalis myofascial flap in the
      treatment of anterior fossa CSF leaks. This flap provides an adequate sized and
      vascularized barrier between the cranial and nasal cavities through which the
      cells of the inflammatory response reach the target area. This technique was used
      in 11 cases with complete success; in-6 patients, repair of the anterior cranial
      base bone defect was performed with split calvarium bone grafts, harvested from
      craniotomy bone. In all the patients, neither the recurrence of the CSF leakage
      nor post-operative meningitis or its recurrence were observed.

PMID- 9245173
TI  - [Angiography in musculoskeletal pathology].

PMID- 9245174
TI  - [24-hour arterial pressure study and diabetic neuropathy and angiopathy of the
      lower limbs].
AB  - AIMS: To study the circadian variation of BP in diabetics with chronic late
      complications (autonomic neuropathy, peripheral neuropathy and macroangiopathy of
      the lower limbs). PATIENTS AND METHODS: We studied 35 NIDDM patients, 22 male and
      13 female, with a mean age of 62.17 +/- 8.66 years, all with hypertension (HBP)
      or with BP levels close to normal, many of them under anti-hypertensive therapy
      (mean BP in clinical measurements: 164 +/- 23.16 mmHg systolic and 92.14 +/-
      11.06 mmHg diastolic). Twenty-four suffer from autonomic neuropathy, 23 from
      peripheral neuropathy and 11 from macroangiopathy of the lower limbs. The control
      group is composed of 10 patients with essential HBP without other observable
      pathology, with a mean age of 68.5 +/- 3.63 years and BP in clinical
      measurements: systolic 192 +/- 15.49 mmHg and diastolic 88 +/- 4.21 mmHg (without
      any previous therapy). The record of the BP circadian profile was made, with the
      use of a Spacelab monitor, model 90207, 5 days after anti-hypertensive therapy
      was suspended. RESULTS: The mean BPs in 24 hours were: control group-systolic BP
      152.6 +/- 13 mmHg and diastolic 79.8 +/- 13 mmHg; diabetics-systolic BP 136.82 +/
      15 mmHg and diastolic 77.4 +/- 8 mmHg. The daily and nocturnal mean BPs were
      158.5 +/- 8.5 and 146 +/- 8.4 mmHg (systolic) and 82.8 +/- 5.7 and 70.9 +/- 5.1
      mmHg (diastolic) in the control group, while they were, in diabetics, 141.3 +/-
      15.7 and 135.6 +/- 16.6 mmHg (systolic) and 79.6 +/- 7.1 and 72 +/- 8.2 mmHg
      (diastolic). In diabetic patients, considering the groups with and without
      autonomic neuropathy, the difference between daily and nocturnal mean BP was 1.6
      vs 9.4 mmHg systolic and 4.9 vs 9.4 mmHg, diastolic. CONCLUSIONS: In both groups,
      the mean BP levels in 24 hours were notoriously lower than those obtained from
      the clinical measurements: the differences were 40 mmHg (control group) and 27.2
      mmHg (diabetics) for systolic BP and 8.2 mmHg (control group) and 14.7 mmHg
      (diabetics) for diastolic. The BP circadian profiles show a lower variability,
      with absence of the nocturnal reduction, specially evident in diabetic patients
      with autonomic neuropathy versus other groups.

PMID- 9245175
TI  - [Life style and occupational risk factors in bladder carcinoma].
AB  - Bladder cancer is a useful model for the study of the relationship between
      lifestyle, occupation and cancer. In the present hospital based case-control
      study, performed in the north of Portugal, we evaluated the role of occupational
      exposure and the effect of different lifestyles as risk factors for bladder
      cancer. We inquired 98 incident cases of bladder cancer (70 men, 28 women) and
      202 hospital controls (100 men, 102 women), selected based on the absence of
      cancer, urinary or lung diseases, and admitted for orthopedic or acute abdominal
      surgery. Demographic, and socio-economical variables were recorded. A detailed
      job history was obtained, and exposure to smoking, alcohol and coffee were
      assessed. Never married subjects and those with higher school degrees presented
      lower risk of bladder cancer. Smoking was significantly associated with cancer
      both in men (OR=2.7) and women (OR=5.7). Alcohol, in contrast, had a protective
      effect, even after adjusting for different confounders. In women, coffee and
      alcohol had a significant multiplicative effect. No particular industrial sector
      was associated with an increased risk of bladder cancer. However, those exposed
      to any of the substances usually considered as risk factors for bladder cancer
      presented higher risks (OR=1.7, 95% confidence intervals: 0.9-3.0). This study
      showed that lifestyles have an important role in the causality of bladder cancer,
      and that occupational exposure probably has less impact in the occurrence of the
      disease in the general population.

PMID- 9245176
TI  - [A retrospective assessment of spinocellular carcinomas of the lip treated by
      roentgenotherapy].
AB  - From December 1965 to December 1987 (22 years), 279 patients with histologically
      confirmed squamous cell carcinoma of the lip were treated in this Department with
      roentgenotherapy. All the patients that had completed the treatment were
      evaluated with a follow-up time of 5 years (n=255). Distribution by age, sex,
      occupation, residence, evolution time of the lesion, localization (upper lip,
      lower lip and commissure), tumoral size and histological grade were analysed.
      Concerning technical conditions and fractionation, we evaluated the type and
      which dose of radiation elicit acute reactions as well as the results of
      radiotherapy (local and cosmetic control). A relation is made between the size of
      the lesion and outcome after treatment. The survival rate at 3 years was 76,6%
      and at 5 years (the usual follow-up period for these patients) was 66%. Disease
      free survival rate at 3 years was 79% and at 5 years was 77,6%.

PMID- 9245177
TI  - [Prognostic factors in intraparenchymatous cerebral hemorrhages. An analysis of a
      hospitalization series].
AB  - We studied 76 patients, with the diagnosis of spontaneous intracerebral haematoma
      confirmed by CT scan, admitted to the Internal Medicine Department of S. Pedro
      Hospital, Vila Real, from 1991 to 93. Neurologic examination, radiological
      characteristics, previous diseases, clinical evolution and treatment were
      analysed to select prognostic factors in relation to length of stay, functional
      status and mortality. Length of stay varied between 1 and 63 days and it is
      estimated that 50% of these patients have a length of stay of less than 22 days.
      In what concerns length of stay, the localisation of haematoma (p < 0.001) and
      presence/absence of systemic infections (p < 0.001) were the most significant
      prognostic factors. The haematomas localised in the brain stem or cerebral deep
      massive and the occurrence of systemic complications were associated to a longer
      hospital stay. None of the parameters analysed were related to functional status
      (Rankin scale), despite the fact that functional impairment was present in 57.1%
      of the patients whose hemorrhage had ventricular blood, compared with 27.5% whose
      hemorrhage had no ventricular blood. In this series, the mortality rate was 29.2%
      and the presence/absence of ventricular blood was the most important prognostic
      factor (p < 0.001). The mortality rate in patients whose haematoma presented
      ventricular blood was five times higher than in the remainder.

PMID- 9245178
TI  - [Mail questionnaires. A useful strategy for the follow-up of patients with a
      cerebrovascular stroke?].
AB  - Although not frequently used in Portugal, postal questionnaires allow the
      collection of information on patient's follow-up. In this study we assessed the
      rate of response and the usefulness of a postal questionnaire in a sample of
      patients with acute stroke. A prospective study was designed and analysed as a
      case-control: postal questionnaires were sent to 138 patients together with a
      randomly assigned stamped or post-free return envelope. The percentage of
      responders was 60% (n=78) and we found no significant differences in response
      rates according to the mailing strategy (58% for stamped and 62% for post-free
      return envelopes, p = 0.786). The time gap between hospital discharge and sending
      of the questionnaire had no significant influence in the response rate. Elder
      patients and women tend to respond more frequently, but these characteristics
      also do not change the response rate. Analysing socio-demographic variables
      reported at the acute phase, we only found differences in response rate for the
      smoking status: smoking was associated with a lower participation. In conclusion,
      the present study showed that a postal questionnaire is a useful method for the
      follow-up of stroke cases and that we must pay special attention to smokers for
      whom alternative strategies of contact or information should be used to increase
      compliance with postal questionnaire follow-up.

PMID- 9245179
TI  - [Familial infection by the hepatitis C virus].
AB  - The aim of this study was to evaluate the prevalence of the antibody to hepatitis
      C virus (HCV) in the relatives of cases of asymptomatic chronic hepatitis C
      infection, detected during routine blood donation, and determine risk factors for
      the presence of the infection in the family setting. Two hundred and eighty-five
      relatives (spouses, offspring, siblings and parents) of 87 index cases were
      studied. Anti-HCV was detected using second generation ELISA and RIBA tests. The
      overall prevalence of anti-HCV in the studied population was 6.7%, higher in
      spouses (11.7%) and lower in the offspring (2.1%). The presence of HCV RNA was
      detected in 12 of 45 index cases, using nested PCR. No increased risk of
      infection was found in the relatives of cases with HCV-RNA positivity. Using a
      logistic regression model, four factors were identified as significantly
      associated with an increased risk of hepatitis C in the relatives: the age of the
      index case, and, as characteristics of the relatives, male gender, past or
      ongoing hepatitis B virus infection, and being a spouse of an index case.

PMID- 9245180
TI  - [Respiratory symptoms in the textile industry. Their prevalence in the Vale do
      Ave].
AB  - Some workers in the textile industry have respiratory symptoms related to their
      occupation. This study is aimed at evaluating the frequency of respiratory
      symptoms in textile industries in the North of Portugal. We evaluated 3529
      workers from 20 factories (19 deal with synthetic fibres and cotton and the other
      deals with sisal.) Among the workers, there were 34.5% with respiratory symptoms 
      24,5% referred nasal symptoms, 22,6% with bronchial symptoms and 12,6%
      associated both. The workers who dealt with cotton presented a higher frequency
      of bronchial symptoms (25,0%) than the ones dealing with synthetic fibres (12,7%
      p < 0,000001). The same was noticed among the workers in the opening and spinning
      areas, who showed a higher frequency of bronchial symptoms (28,3%) than the ones
      in weaving areas (12,7% p < 0,000001). We did not find any differences concerning
      the frequency of symptoms among the workers handling both natural fibres (cotton
      and sisal). Individually all the symptoms were more frequent among the workers
      handling natural fibres. The most frequent symptom depended on the fibre. Cough
      was more frequently mentioned among the workers handling synthetic fibres (9.6%)
      and cotton (15.7%). Among the workers who handle sisal, dyspnea was the most
      frequently mentioned (16.9%). Productive cough was the most frequent association
      (7.2% sisal; 2.8% synthetic; 8.0% cotton), and the association between dyspnea
      and wheezing the least mentioned (6.4% sisal; 0.5% synthetic; 5.9% cotton). The
      workers with bronchial symptoms (synthetic fibre and cotton) have more years of
      exposure and greater smoking habits. In a covariance adjusted for age and smoking
      habits, the workers with bronchial symptoms, exposed to cotton have more years of
      exposure.

PMID- 9245181
TI  - [The healthy life].
AB  - This study is based on a comparison of the habits and opinions of a group of
      pupils on entering the Damaia Preparatory School (5th and 6th years of education)
      and of the same group on leaving this School. Its aim is to contribute towards an
      adequate education for health at school in order to promote healthy living
      habits. The study was based on the comparison of data obtained from two random
      samples, chosen from the same group of pupils when entering (n1 = 36 out of a
      total of 368) and leaving (n2 = 32 out of a total of 164) the above mentioned
      school. The collection of data was carried out by means of a multiple-choice
      questionnaire given to a total of 532 pupils. The results demonstrated that the
      frequencies have changed in the following way: a) bathing has increased; b) tea
      drinking has decreased; c) the image of the teacher as a smoker has become less
      frequent; d) the number of pupils who have tried alcoholic beverages has
      increased; e) mother's smoking habits have increased. The other trends that were
      found in the study showed that there were no significant changes in either the
      behaviour or opinions that had been studied.

PMID- 9245182
TI  - [Tumor markers (advances and limits)].
AB  - The author reviews and discusses the clinical utility of the major tumor markers.
      In spite of advances in the analytical systems, until recently there were no
      tumor markers that detect early stage cancer or that were absolutely specific or
      diagnostic for malignancy. Most of them are normal glycoproteins (that accompany
      the genetic deregulation of carcinogenesis) which are released into the blood and
      depend on liver function for their catabolism. Therefore such assays are of no
      use for screening healthy populations and a normal value does not exclude cancer.
      Their use may be of great help to the clinician in a number of ways: (1) primary
      staging of patients known to have cancer; (2) screening of high-risk individuals
      for the presence of some malignancies; (3) monitoring of the effectiveness of
      therapy; (4) patient's follow-up for early detection of relapses or metastases;
      (5) prognostic indexes; and (6) immunodetection of metastatic sites. Whatever the
      applications, a good clinical judgement is crucial for the use of these assays,
      with a critical look at the extent to which they contribute to a favorable
      outcome. At present, we think that their use in check-up studies should be
      avoided.

PMID- 9245183
TI  - [The pacemaker syndrome].

PMID- 9245184
TI  - [Lipoprotein(a). Its importance as an additional atherosclerosis marker].
AB  - Lipoprotein(a) is one of the best examples of heterogeneity of lipoproteins. It
      presents pre-beta electrophoretic mobility in agarose gel, similar to Very Low
      Density Lipoproteins, it is found in High Density Lipoproteins due to its
      hydrated density greater than 1,063 and resembles Low Density Lipoproteins in its
      size and lipid composition. However, Lp(a) is unique in that it contains an
      additional distinct antigen, the apo(a), attached to apoB100 by one disulphide
      bridge. The apo(a)-glycoprotein has recently been shown to have a striking amino
      acid sequence homology with plasminogen; Lp(a) seems to be a potential bridge
      between atherosclerosis and thrombosis fields and interest in Lp(a) has greatly
      increased since then. The new knowledge on the structure of Lp(a) being more and
      more rapidly acquired should facilitate our understanding of the mechanisms of
      its atherogenicity and its physiopathological role. Metabolic studies have made
      it clear that Lp(a) is not a product derived from other apoB-containing
      lipoproteins, but is secreted by the liver as a distinct mature lipoprotein.
      Concerning the immunological techniques available to assay Lp(a) they need to be
      standardized and it is still necessary to define what is meant by the
      pathological threshold for Lp(a), which will certainly depend on the choice of
      the standard antiserum and immunological method used.

PMID- 9245185
TI  - [Digoxin. The drug of choice for the in-utero treatment of paroxysmal
      supraventricular tachycardia].
AB  - Fetal tachyarrhythmia may constitute a risk for the fetus, therefore early
      treatment is indicate for all cases of tachydysrhythmia, with or without hydrops,
      in order to prevent irreversible hydrops. A case report is described of
      supraventricular paroxysmal tachycardia with digoxin in utero therapy in which
      pharmacological intervention was successful. Some comments are regarding the
      experience of the multidisciplinary team at Bissaya-Barreto Maternity in the
      treatment and orientation of fetal tachydysrhythmias.

PMID- 9245186
TI  - [Aplastic anemia. Alternative treatment by bone marrow transplantation].
AB  - We report a case of a 25-year-old woman, with the diagnosis of severe aplastic
      anemia without a histocompatible sibling donor for bone marrow transplantation.
      The patient has been treated successfully with a combination of two
      immunosuppressive agents, cyclosporine and antilymphocyte globulin, after not
      responding to primary therapy with corticosteroids and growth factors. She showed
      a complete response to treatment, with transfusional independence, after a follow
      up of 14 months. The pathophysiology of aplastic anemia, the mechanism of action
      and secondary effects of these treatments are discussed.

PMID- 9245187
TI  - [Referral to the psychiatrist in the general hospital: a psychodynamic approach].
AB  - INTRODUCTION: It is not clear as to the process by which the psychiatrist
      attracts referrals and the reasons and motivations that doctors have for
      referring or not. This study describes the modus operandi of referrals to the
      psychiatrist in the context of a university general hospital. METHOD: A semi
      structured interview was carried out on 50 doctors (35 male, 15 female) from the
      teaching hospital of the Universidade Estadual de Campinas, Brazil. Data was
      analyzed qualitatively, by means of content analysis, according to the
      psychodynamic approach. RESULTS: Some referrals need to be worked through in
      order for the doctor to overcome his resistance. Others are automatic: because
      something moved him deeply, the doctor directs his anguish and responsibility
      outside himself, without realizing the motives that lead him to do so.
      CONCLUSION: Referral is used in a variety of ways and different things are
      expected of the psychiatrist, all influenced by unconscious aspects of the
      patient-doctor-specialist triad.

PMID- 9245188
TI  - [Critical evaluation of the use of antidepressives in childhood].
AB  - In the introduction the authors study some technical, methodological, ethical,
      administrative and marketing problems about the evaluation and investigation in
      child and adolescence psychopharmacology. They make a revision and critical
      evaluation about. As a whole the clinic use of antidepressive drugs in childhood
      psychiatry. Then, some open and controlled trial about tricyclic antidepressives
      are evaluated. After this, the authors present the most important advances about
      the open and controlled clinic trials with several antidepressives: tricyclic,
      tetracyclic, ISSR and MAO-Inhibitors and other drugs (placebo response,
      psychotherapy, imipramine, nortryptiline, amitriptyline, fluoxetine, MAO
      Inhibitors, lithium, mianserin, maprotyline, etc.). Beside, placebo effect,
      response prediction factors, biologic markers, diagnostic criteria, evaluation
      methods and technics, drugs associations, clinic types of child depression, etc,
      are studied. In the last, the authors present some clinical conclusions about
      this subject.

PMID- 9245189
TI  - [Tardive dyskinesia: a review].
AB  - Tardive Dyskinesia (TD) is a iatrogenic syndrome of involuntary movement that
      occur in association with chronic neuroleptic use. The diagnosis and ongoing
      assessment of TD severity is complicated by a host of methodological problems.
      Orofacial movements are most frequent, although other body areas, limbs, neck and
      trunk, may be involved. The prevalence for TD varies widely from study to study,
      the estimated average prevalence is a 20%. The pathophysiology of TD remains
      poorly understood despite the numerous theories have been proposed. One of the
      most consistently identified TD risk factors is age. This factor is independent
      of drug exposure although both are often confounded. Currently no consistency
      effective treatment has yet been found and the most important treatment consist
      of gradual neuroleptic drug-dose reduction and, where possible, complete
      withdrawal.

PMID- 9245190
TI  - [Phrenitis in Greco-Latin medicine].
AB  - Since the times the Hipocraticum Corpus was written, Phrenitis or Mental
      Confusion was described as a mental disorder related basically to fever, but also
      related to craneal traumatisms an others somatics ethiologies. The theorical
      background of the different schools was the same, the Phisis and Humors doctrine,
      but the results of their works were quite different. Cos school had a biographic
      approach, Cnido a systematic one, and Eclectics blended both with emphazis in
      treatment.

PMID- 9245191
TI  - [Psychiatric symptoms in acute myeloblastic leukemia: a clinical case].
AB  - The psychiatric manifestations of hematological diseases are interesting because
      of their diverse presentations, complex treatment, pharmacological interactions,
      and frequent infectious complications. A patient with acute myeloblastic leukemia
      (AML) presented psychiatric manifestations of sudden onset and psychotic
      characteristics. The absence of organic lesions in routine neuroimaging studies
      suggested an added schizophreniform disorder. Further neurological study using
      more sensitive methods disclosed herpetic encephalitis as the origin of delirium.
      This case illustrates how early diagnosis, although not always possible, is
      important if major sequelae are to be avoided. Likewise, it is important to make
      a through search for organic factors in psychotic pictures that appear in the
      context of systemic disease.

PMID- 9245192
TI  - [Serotonergic function in endogeneity of depression].
AB  - OBJECTIVE: This study employed an alternative method for assessing serotonergic
      function in depression. The neuroendocrine responses to acute intravenous
      administration of the serotonin (5-HT) reuptake inhibitor clomipramine were
      assessed in patients with Major Depression with Melancholia (DMM) and matched
      subjects with Major Depression (DM) (without Melancholia) and Dysthimic disorder
      (TD). METHOD: 10 patients who met DSM III-R criteria of DMM, 10 patients with DM
      and 10 with DD matched for age and sex received 12.5 mg of intravenously
      administered clomipramine. Prl, Cortisol and GH were measured during the next 135
      minutes. We divided the samples using the Newcastle Scale. RESULTS: The DMM
      patients had significant blunting prolactin responses to clomipramine compared
      with the other patients. Most of the major depression patients without
      melancholia were neurotic depressions according to the Newcastle Scale. There was
      a negative correlation between endogeneity and prolactin response. CONCLUSIONS:
      These data support the hypothesis that DMM patients have abnormal neuroendocrine
      responses to the intravenous administration of the 5-HT reuptake inhibitor
      clomipramine, and that there is an association between endogeneity and prolactin
      response.

PMID- 9245193
TI  - [Treatment with tianeptine for depressive disorders in the elderly].
AB  - Depression is frequent in the elderly but difficult both to diagnose and treat
      due to a number of distinctive features. Tianeptine is a novel antidepressant
      with a reverse mode of action to that of the selective serotonin reuptake
      inhibitors yet with proven efficacy and safety. 63 elderly patients (mean age:
      68.8 years; range: 65-80 years) with depressive symptoms (major depression:
      55.6%; dysthymia: 44.4%) were included in a 3-month open multicenter study with
      tianeptine (25 mg daily). 43 patients (68.2%) completed the study. There were no
      drop-outs due to side-effects. Total Montgomery and Asberg depression rating
      scale scores were significantly decreased (p < 0.01) on day 14, with a response
      rate of 76.7%. Improvements were also observed in anxiety and cognitive
      performance. Side-effects were seen in only 11.7% of patients, with no changes in
      laboratory or ancillary safety parameters. Tianeptine is thus effective and well
      tolerated in this category o patient.

PMID- 9245194
TI  - [Construct validity and reliability of the Newcastle Endogeniety Index I].
AB  - The authors study the construct validity of the Newcastle's Endogeneity Index
      (NEI). They use the correlation matrix published originally by Carney et al
      (1965). The results show a high reliability of the NEI (alpha = 0.77). The
      Factorial Analysis shows two factors, not independent, that explain a 45% of the
      total obtained variance; it seem to indicate a drop construct validity of the
      NEI. The authors discuss the validity of the endogenous/neurotic classification
      of the depression because of the high agreement the NEI and the clinical
      criterion.

PMID- 9245195
TI  - [Psychiatric syndromes and social factors in primary care].
AB  - A study was carried out in order to identify the main dimensions of psychiatric
      symptoms in primary care and to study their relationship with demographic
      characteristic and life events and difficulties. 233 consecutive patients without
      previous psychiatric contact with their doctor were assessed using the Present
      State Examination-9 (PSE-9) and the Life Events and Difficulties Schedule in 10
      primary care offices. A factor analysis was carried out on the items of the non
      psychotic part of the PSE-9. Four main dimensions (depression, non-specific
      symptoms, lack of confidence and self-criticism, and specific anxiety) were found
      explaining the 53.7% of total variance. Acute and chronic life events are
      associated with the depression, non-specific symptoms, and lack of confidence and
      self-criticism dimensions after controlling for the effect of clinical variables
      and demographic characteristics, and previously or currently married shows a
      statistical significant trend to signification in its association with the non
      specific symptom dimension after controlling for the effect of clinical variables
      and life events.

PMID- 9245196
TI  - Maurice Stacey 1907-1994.

PMID- 9245197
TI  - [The need of prolonged BCG treatment in superficial bladder cancer is suggested
      by the development of a peripheral immune response induced by BCG].
AB  - Optimal duration of immunotherapy treatment by BCG for the prevention of
      recurrences of superficial bladder cancer is still unknown. We have studied the
      evolution and duration of the cellular immunity response at the peripheral level
      after BCG intravesical instillations. Our results show that immunity activation
      after BCG is of short duration and don't take more than 6 months. Our results
      support, strengthen and partially allow to explain the utility of maintenance
      treatment by BCG following 6-weekly instillations.

PMID- 9245198
TI  - [Recurrence following radical surgery for prostatic cancer. Analysis of clinical,
      biological and anatomo-pathological prognostic factors].
AB  - To better characterize risk factors of progression (or recurrence) of prostate
      cancer after radical surgery, we analysed clinical and biological preoperative
      characteristics and post-operative pathology results in a series of 179 patients
      who underwent radical prostatectomy between January 1, 1993 and December 31,
      1994. The mean follow-up in the series is 36 months (24-36). 39 patients treated
      before radical prostatectomy by hormonotherapy or surgery (TURP, TULIP) were
      excluded from analysis. 28 patients treated with immediate adjuvant therapy were
      also excluded from the study on risk factors of recurrence. Clinical understaging
      is 37% (50/134 patients with stage T1-T2 have extracapsular extension or invasion
      of seminal vesicles). Preoperative PSA value is related to the pathologic stage.
      Extracapsular disease was found in 17% and 46% when PSA was < 4 ng/ml or > 10
      ng/ml respectively, thereby confirming the poor staging value of preoperative PSA
      alone. Analysis of the surgical margins demonstrates a statistically significant
      difference (p = 0.018) between patients with a preoperative PSA < 10 ng/ml (22%
      of positive margins) and those with a PSA > 10 ng/ml (42% of positive margins).
      Predictive factors of recurrence were analyzed in the 112 patients who have not
      received pre- or postoperative treatment. The respective impact of clinical
      stage, preoperative PSA value, Gleason score, invasion of prostatic apex,
      capsular perforation, surgical margins, invasion of seminal vesicles or of pelvic
      lymph nodes, and invasion of intraprostatic, intracapsular or extraprostatic
      nerves were evaluated. In T3 cases, we observe 50% recurrence (but only 4
      patients fall into this group) versus 14% in clinically localized tumors (T1c
      T2c). No recurrence is detected when preoperative PSA is < 4 ng/ml; on the
      contrary 21% of patients with a PSA > 10 ng/ml recurred. Infiltration of the apex
      does not influence prognosis. In our experience, capsular perforation is a worse
      prognostic factor than positive surgical margins, the respective rate of failure
      being 25% and 17% respectively. Invasion of extraprostatic nerves increases the
      risk of failure compared to capsular perforation alone (31% vs 18%). Seminal
      vesicles invasion significantly worsens prognosis (50% vs 13% recurrence
      respectively; p = 0.024). All patients with positive lymph nodes recurred (p =
      0.001).

PMID- 9245199
TI  - [Recurrent urethral stenosis treated with a Urolome Plus stent implantation:
      intermediate multicenter follow-up].
AB  - We present the medium-term results of 33 patients treated with Urolume Plus
      urethral stent between August 1990 and June 1996 in 9 Belgian and Luxembourg
      centers. They all had previous treatments for bulbo-membranous urethral
      stricture, but without sustained benefit (dilatation, internal urethrotomy,
      or/and urethroplasty). The mean age of the stricture was 5.4 years (+/- 4). The
      stent was inserted easily during a short hospitalisation. Median time of follow
      up is two years (6 months to 4 years). Maximum flow rate at last follow-up was
      20.7 ml/sec (+/- 7), and 83.3% of the patients were satisfied with the stent. In
      70% of the cases, the stent achieved its purpose of maintaining a good urethral
      lumen. In 5 patients (15.15%), stricture recurred inside the stent and in 2
      patients (6.06%) a new stricture appeared on another site. Among these 7
      patients, 5 were satisfactorily treated by endoluminal resection (4 cases) or
      dilatation (1 case). There were 2 real failures (= 6%): one patient who has
      refused any complementary endoscopic treatment and the other one who is still
      undergoing repeated urethral dilatations. Having respected the right indications
      for this device, we are satisfied of the results. It is a good alternative after
      failure of other treatments for bulbar-membranous stricture.

PMID- 9245200
TI  - [Urinary stress incontinence and celioscopy: 20-month-experience of an original
      technique of colposuspension via extraperitoneal endoscopy. "Pantalon
      technique"].
AB  - The authors describe an original extraperitoneal endoscopic colpo-suspension
      procedure for the treatment of stress urinary incontinence in women, by the use
      of a Y-shaped non-absorbable mesh (polypropylene). The short Y arms are sutured
      to the front-lateral walls of the vagina, the Y basis is grasped through a short
      suprapubic incision involving the skin and subcutaneous fat with a pair of
      forceps to perforate the muscle aponeurosis. This technique allows an adequate
      and firm tension on the mesh under endoscopic control. The basis of the mesh is
      then sutured at the pubic bone insertion of the rectus abdomini. So far, we have
      performed 28 operations--between April 1995 and December 1996. The objective cure
      rate is 88.5%. Two laparotomy had to be performed.

PMID- 9245201
TI  - [Ureteral triplication and contralateral ureteral duplication. Apropos of a
      case].
AB  - Authors report a case of right ureteral triplication complicated with right
      hydronephrosis of the upper kidney and vesico-ureteral reflux concerning the
      middle kidney. Surgical technique is illustrated and a brief review of literature
      completes this case-report.

PMID- 9245202
TI  - [Aspergillus prostatitis and prolonged corticotherapy. Apropos of a case report].
AB  - Aspergillosis prostatitis is rare but more frequent to immunodeficiency people.
      We report a case of aspergillosis prostatitis associated with pulmonary
      tuberculosis, after a corticosteroid treatment for retroperitoneal fibrosis to
      Methysergide.

PMID- 9245203
TI  - [PSA level of the transitional zone: a new marker especially reliable for the
      detection of prostatic cancer].
AB  - The extensive use of serum prostate specific antigen in early PCa diagnosis has
      been limited by the far from perfect sensibility and specificity of this test.
      The value of prostate specific antigen density (PSAD) to enhance prostate cancer
      detection in patients with PSA serum levels below 10 ng/ml is limited due to
      controversial results. We have compared the value of PSAD of the transition zone
      (PSA-T) dividing serum PSA by transition zone volume to the PSAD for early
      prostate cancer prediction in patients with PSA levels under 10 ng/ml. PSAD and
      PSA-TZ were calculated in patients with histologically proved located prostate
      cancer or with benign histology. We have defined a cut-off value of 0.35 ng/ml/cc
      for PSA-TZ with both a sensitivity and a specificity in predicting prostate
      cancer of nearly 90%. For PSAD around 0.15 ng/ml/cm3, PSA-TZ value was
      significant in prostate cancer. This study showed that PSA-TZ could be a new
      accurate parameter for prostate cancer prediction in patients with PSA below 10
      ng/ml.

PMID- 9245204
TI  - [Retroperitoneal schwannoma. Diagnostic and therapeutic outcome].
AB  - Two cases of retroperitoneal benign schwannoma are described with a review of
      literature. Are analysed the clinical and anatomopathologic features of this rare
      tumor and the methods of diagnosis. The treatment is the surgical ablation of the
      tumor commonly easy and complete. When malignancy is established, adjuvant
      procedures add little to life expectancy and total surgery is done likely to be
      effective.

PMID- 9245205
TI  - History of nephrology 2. Reports from the 1st Congress of the International
      Association for the History of Nephrology. Kos, Greece, October 14-16, 1996.

PMID- 9245206
TI  - [Parenteral nutrition therapy. Energy and non-energy actions of carbohydrates and
      fats].
AB  - The object of this review is to demonstrate the non-nutritional importance of
      carbohydrates and fat as they represent the classic energy carriers in parenteral
      nutrition. Concerning the pathophysiological changes of organ metabolism and
      intermediary metabolism as well as the pharmacological function of this nutritive
      substrates it is necessary to adjust parenteral nutrition strategy to various
      clinical pictures. The major goals of parenteral applicated carbohydrates are to
      avoid hyperglycemia, to return the increased hepatic glucose production during
      trauma and sepsis back to normal, and to reduce protein catabolism. Realizing
      this goals the dosage of glucose infusion underlies close metabolic borders
      depending on the present disease. Because of favourable effects of hepatic
      glucose and protein metabolism, xylitol, a non-glucose polyol, represents an
      useful alternative energy source to glucose. The non-energetic nutrition therapy
      with fat consists of application of the essential fatty acids linoleic and alpha
      linolenic acid and considers the immunmodulatory effects of various fatty acids
      as precursors in the eicosanoid metabolism. As demonstrated at the organ systems
      of liver and lung this pharmacological effects of any lipid infusion might
      influence specific organ functions.

PMID- 9245207
TI  - [The clinical pharmacology of mivacurium].
AB  - Mivacurium is a short-acting, nondepolarising muscle relaxant of the
      benzylisoquinoline type that undergoes rapid breakdown by plasma cholinesterase.
      After 2.5 times the ED95 (0.2 mg/kg), tracheal intubation can be accomplished
      within 2-3 min following injection. The ensuing DUR 25% (i.e., time from
      injection to 25% recovery of control twitch tension) is three times as long as
      with succinylcholine. The principal side effects of mivacurium are facial
      flushing and a transient fall in blood pressure due to moderate histamine release
      following doses 3-4 times the ED95. In patients with end-stage liver or renal
      disease as well as those with atypical plasma cholinesterase, the duration of
      action of mivacurium is prolonged.

PMID- 9245208
TI  - [Safe handling of the laryngeal mask airway in eye surgery].
AB  - BACKGROUND: We prospectively used the laryngeal mask airway (LM) in eye surgery
      to evaluate: 1) the limits of safe handling; 2) the feasibility of its use in
      long operative procedures, and 3) whether patients with higher anaesthetic risk
      (hypertension, asthma, children) may profit from the LM. METHODS: In 792 patients
      leak pressure, cuff volume, duration of anaesthesia, and complications were
      noted; 33 were children under 10 years of age, 100 had hypertension or severe
      asthma. In 54 patients cuff volume was increased to measure its influence on leak
      pressure; in 241 leak pressure was also measured at the end of the procedure; in
      31 cuff pressure was measured under standard conditions over time; in 7 dead
      space was evaluated with the BANALYZER program; and in 300 blind endotracheal
      suction was attempted through the LM. RESULTS: Limits for the safe use of the LM
      were a leak pressure < 12 cm H2O combined with insufficient spontaneous
      ventilation (CO2et > 7 vol.%; n = 14), dislocation with gastric inflation (n =
      2), and bronchial secretions (n = 1), as blind suctioning of the trachea through
      the LM was possible in only 1 out of 300 attempts. These limits could be
      recognised before the start of the operation in most cases. Laryngospasm or
      closure of the glottis (n = 36, 4.5%) was treatable and did not necessitate
      abandoning the use of the LM. Mean leak pressure was 17.7 +/- 4.8 cm H2O, showing
      a comparable distribution in adults and in children and being improved mainly by
      position changes of the LM, but not by changes in cuff volume. No gas leak
      occurred when the individual peak inspiratory pressure was equal to or lower than
      the measured leak pressure except in children. Dead space was almost halved by
      the LM compared to a face mask (90 +/- 13 vs. 162 +/- 31 ml; P < 0.05), allowing
      spontaneous breathing to be adequate even when manual assistance of ventilation
      was not possible (n = 14, 1.8%). In patients with sufficiently high leak
      pressures, the LM was safely used for long operations (up to 240 min), as leak
      pressure did not change over time. When only a low leak pressure could be
      achieved, deep breaths could be delivered by prolongation of the inspiratory
      time, thereby preventing atelectasis if tidal volume was limited. Cuff pressure
      rose to about 100 cm H2O within 60 min and should be monitored. In children, air
      was aspirated intermittently out of the stomach in procedures longer than 30 min;
      in adults, we monitored and buffered gastric contents where necessary. In
      patients at risk, the LM stimulates the circulation and bronchial reactivity less
      than an endotracheal tube. Children could be discharged earlier from the recovery
      room (0.45-1.5 h vs. > or = 2 h after neuromuscular relaxation and intubation).
      CONCLUSION: Limits for the use of the LM in eye surgery are delineated. Within
      these limits, the LM offers control over the airway comparable to that of an
      endotracheal tube with less stimulation. The LM has to be applied by an
      experienced user, and has advantages in eye surgery.

PMID- 9245209
TI  - [Interaction of nimodipine and propofol in dogs. Hemodynamics and
      cardiodynamics].
AB  - Nimodipine is frequently used for treatment of cerebral vasospasm in patients
      undergoing intracerebral vascular surgery and during intensive care therapy of
      patients with subarachnoid haemorrhage. Propofol is being increasingly used as a
      hypnotic drug in neuroanaesthesia and for sedation in critically ill patients.
      There is evidence of a propofol effect on voltage-dependent calcium channels;
      hence, the administration of propofol may interact with the haemodynamic effects
      of nimodipine. We investigated the haemodynamic interactions of both compounds in
      chronically instrumented dogs. METHODS: Five mongrel dogs were chronically
      instrumented for measurement of heart rate (HR), left atrial (LAP), aortic (ABP),
      and left ventricular pressure (LVP), LV dP/dt, cardiac output (CO), systemic
      vascular resistance (SVR), coronary blood flow velocity (CBFV), and myocardial
      wall-thickening fraction (WTF). After complete recovery from surgery and
      assessment of normal resting blood gas values and temperature, all animals
      received on separate days either propofol 30 mg/kg.h (P), nimodipine in two
      maintenance doses in the awake state (N), or the combination of nimodipine and
      propofol (N+P). The maintenance doses of nimodipine in N and N+P were 1 and 2
      micrograms/kg.min for 40 min each after a bolus of either 10 or 20 micrograms/kg
      min over 2 min. Measurements were performed as controls, in the middle (20 min),
      and at the end (40 min) of each maintenance infusion of nimodipine or at
      equivalent points in time in group P (Fig. 1). Animals receiving propofol were
      mechanically ventilated after endotracheal intubation. Blood gas values were kept
      within the normal range. All data were analysed with repeated measures of ANOVA
      followed by student's t-test with Bonferroni correction. RESULTS: There was no
      statistically significant difference for any of the measured parameters between N
      and N+P or between the two maintenance doses of nimodipine (Table 1). HR was
      significantly higher with both doses of nimodipine in the awake state compared to
      the control values (123 +/- 7.1 and 146 +/- 6.4 vs 78 +/- 2.4/min). The
      administration of nimodipine with and without propofol led to a significant
      increase in CBFV (Fig. 2). However, there was no difference in CBFV between
      nimodipine in the awake state and in combination with propofol (Fig. 2).
      CONCLUSIONS: We conclude that administration of propofol does not alter the
      systemic haemodynamic and regional myocardial effects of a nimodipine infusion in
      a dose of 1 or 2 micrograms/kg.min in chronically instrumented dogs.

PMID- 9245210
TI  - [Combination anesthesia and bronchial tranport velocity. Effects of anesthesia
      with isoflurane, fentanyl, vecuronium and oxygen-nitrous oxide breathing on
      bronchial mucus transport].
AB  - The mucociliary escalator of the lung is an important protective transport system
      by means of which inhaled particles and microorganisms are removed from the
      tracheobronchial system. In general, it is assumed that anaesthetics inhibit
      mucociliary clearance [3,5,6,19,27]. In the present prospective study the effect
      of combination anaesthesia with isoflurane, fentanyl, vecuronium, and nitrous
      oxide-oxygen mixture on bronchial mucus transport velocity (BTV) was
      investigated. PATIENTS AND METHODS: 10 patients undergoing major abdominal
      surgery were included in the study. The study was approved by the ethics
      committee of our hospital. In all patients anaesthesia was induced with propofol
      (1-2 mg/kg), fentanyl (0.2-0.3 mg/kg) and vecuronium (0.1 mg/kg). After
      intubation anaesthesia was maintained with 1.5 MAC isoflurane and repeated doses
      of fentanyl (0.1-0.2 mg) and vecuronium. Ventilation was assisted with a 2:1
      mixture of nitrous oxide and oxygen. The BTV was measured preoperatively in the
      conscious patients one day before surgery while they received local anaesthesia
      with 10 ml of 1 percent lidocaine and postoperatively while they received
      intubation anaesthesia. BTV was determined with a small volume of albumin
      microspheres labeled with technetium-99m, which was deposited on the dorsal
      surface at the lower ends of the right and left main bronchi via a catheter
      placed in the inner channel of a fibre-optic bronchoscope [15]. RESULTS: Table 1
      provides information about age, application of anaesthetics and duration of
      mechanical ventilation of the patients. The preoperative and postoperative BTV
      values showed no significant differences (Fig. 1). CONCLUSIONS: Combination
      anaesthesia with isoflurane, fentanyl, vecuronium, and O2:N2O does not influence
      BTV in patients with healthy lungs.

PMID- 9245211
TI  - [Mechanical myocardial support systems 1997: an overview of inta-aortic balloon
      counterpulsation to implantable left ventricular support systems].
AB  - The development of cardiopulmonary bypass (CPB) to support the systemic
      circulation during cardiac surgical procedures became a clinical reality in 1953.
      Although the use of CPB for the treatment of post-infarction cardiogenic shock
      met with little success, intra-aortic balloon counterpulsation was used
      successfully in 1968 to reduce ischaemic injury in a patient with cardiogenic
      shock. Today, a broad spectrum of circulatory assist devices for short- and long
      term application is available. Three major indication groups for the use of
      support devices are established. In low-cardiac-output syndrome after cardiac
      surgical procedures, short-term devices are utilised to enable myocardial
      recovery. In transplantation candidates suffering from drug-resistant pump
      failure, the implantation of long-term devices as a bridge to heart
      transplantation is indicated, and in NYHA class IV patients with
      contraindications to heart transplantation, the implantation of long-term devices
      as an alternative to transplantation is under discussion. In the literature, post
      cardiotomy support survival is less than 30% on average. About 70% of
      mechanically bridged patients have survived to undergo heart transplantation and
      were transplanted with over 90% survival. Major problems during mechanical
      support are infection, bleeding, and thromboembolism. In view of patients'
      natural course without support, these clinical results are favourable.

PMID- 9245212
TI  - [Opioid intoxication. Inappropriate administration of transdermal fentanyl].
AB  - A 22-year-old male suffering from neuropathic pain in his right leg had
      sufficient analgesia with oral tilidin 300 mg per day. Nevertheless, the general
      practitioner decided to change the therapy to transdermal fentanyl. Having cut a
      fentanyl patch (50 micrograms/h) into pieces, he applied one-fourth of the patch;
      60 min later the patient developed signs of opioid intoxication, including heavy
      sedation, nausea and respiratory depression. After the patch was removed another
      60 min later, the patient made a complete recovery. The risks following
      inappropriate application of transdermal fentanyl are discussed.

PMID- 9245213
TI  - [Spinal anesthesia for ambulatory arthroscopy. The view of the patients: results
      and patient's viewpoint].
AB  - Spinal anaesthesia for outpatients is a method that is not favoured in several
      reports without having representative data. It was our desire to investigate
      whether this method could be used without having dangerous side effects. METHOD:
      After knee arthroscopy in spinal anaesthesia, patients received a questionnaire.
      The questions could be answered anonymously in a "yes-no" fashion. Additionally,
      the patients received an accompanying explanation concerning the so-called health
      structure law. RESULTS: Of a total of 85 patients; 70 sent back the
      questionnaire. Temporary neck stiffness was seen in 1 case, hypotension in 5,
      nausea in 2, emesis in 5, and fever in 3. Twelve patients had headaches, 67 were
      in good condition upon leaving the clinic. Sixty-four would prefer spinal
      anaesthesia for a subsequent similar procedure. Nine patients treated themselves
      at home, which is not permitted in outpatient procedures; 7 of these had
      headaches that may have been secondary to the dural puncture. No severe side
      effects were seen. CONCLUSIONS: 1. Spinal anaesthesia is a method that can also
      be performed in out-patients. 2. an increased incidence of post-dural-puncture
      headaches may be seen due to the early mobilisation of the patients; 3. the
      patient must be treated by a second person; 4. premedication must be performed 2
      days before the procedure to determine ASA status; and 5.better co-operation
      between surgeons and anaesthesiologists must be sought.

PMID- 9245214
TI  - [Etomidate inhibits neuronal potassium channels in humans].
AB  - INTRODUCTION: There is no data available on the action of etomidate on ion
      currents in human neuronal cells. Therefore the effects of etomidate on a human
      neuronal delayed rectifier potassium current were investigated. METHOD: Outward
      rectifying potassium currents of human neuroblastoma SH-SY5Y cells were measured
      using the whole cell patch-clamp technique. Cells were grown in RPMI-medium
      (+Pen/Strep and FCS) at 37 degrees C and 5% CO2. The holding potential was -80
      mV. Potassium currents were evoked by depolarizing the membrane potential to
      values from -50 mV to +90 mV in 10 mV steps using an EPC-7 patch-clamp amplifier
      (List medical electronics) and pclamp version 5.71 (Axon instruments). RESULTS:
      Etomidate differentially inhibited steady-state and peak potassium current with
      IC50-values of 170 microM for peak current suppression and 120 microM for steady
      state current respectively. Etomidate induced inactivation-like behaviour of the
      potassium current and changed the voltage dependence of potassium current
      activation. CONCLUSION: The results demonstrate that etomidate has more than one
      effect on the potassium current, indicating the complexity of general anaesthetic
      actions on neuronal targets. The actions of etomidate on human neuronal potassium
      currents may potentially contribute to the myocloni observed with this general
      anaesthetic agent during induction of anaesthesia.

PMID- 9245215
TI  - [The Mallampati Score. Prediction of difficult intubation in otolaryngologic
      laser surgery by Mallampati Score].
AB  - The Mallampati score (MS), later modified by Samsoon and Young, is a common
      method used to predict difficult intubation. We tested its predictive value in
      otolaryngologic (ENT) laser surgery. METHODS: Ninety-one patients scheduled for
      elective ENT laser surgery had the modified MS noted prior to induction in the
      supine position, with the tongue fully protruded and phonating "ah"; 22 patients
      were female, 69 male. The mean age was 54 +/- 15 (6-84) years, height 171 +/- 9
      (130-190) cm, and weight 72 +/- 21 (20-99) kg. After a standard induction, the
      laryngoscopic view was graded according to Cormack and Lehane (C&L). An
      intubation was considered difficult if the C&L score was > or = 3, i.e., no part
      of the glottis seen during laryngoscopy. The hypothesis tested was that a MS > or
      = 3 (i.e., only the base of the uvula or nine of the uvula was seen) is
      predictive of difficult intubation in this group of patients. This chi-square
      test was used for calculation of significance. RESULTS: All intubations were
      performed in less than three attempts, and no C&L score of 4 (i.e., not even the
      epiglottis seen during laryngoscopy) was observed; 10 patients had a C&L score >
      or = 3, i.e., a difficult intubation according to our definition. Sixty-two
      patients had a MS < or = 2; of these, 4 (= 6%) were difficult to intubate. Twenty
      nine patients had MS > or = 3; of these, 6 (= 21%) were difficult to intubate.
      This difference was significant (chi-square = 4.1, P < 0.05). CONCLUSION:
      Difficult intubation was significantly more common in patients with MS > or = 3.
      Low sensitivity (60%) and specificity (72%) limit the clinical value of this
      test, however.

PMID- 9245216
TI  - [Nitric oxide].

PMID- 9245217
TI  - [New developments in anesthesiology and intensive care. IX. International
      Heidelberg Symposium, Heidelberg, 14-16, 1996].

PMID- 9245218
TI  - [The importance of quality of whole blood and erythrocyte concentrates for
      autologous transfusion. Remarks on the work of R. Karger and V. Kretschmer,
      Anaesthesist (1996) 45:694-707].

PMID- 9245219
TI  - [Principles of physician's liability as it applies to the anesthetist. Remarks on
      the work of G. H. Schlund, Anaesthesist (1996) 45:789-97].

PMID- 9245220
TI  - [An empty stomach is necessary in the delivery room].

PMID- 9245221
TI  - [Preoperative withdrawal of Marcumar].

PMID- 9245222
TI  - Monitoring warfarin therapy in patients with lupus anticoagulants.
AB  - BACKGROUND: Recommended therapeutic international normalized ratios (INRs) for
      oral anticoagulation in patients with lupus anticoagulants who sustain a
      thromboembolic event are controversial. Patients with lupus anticoagulants often
      have a prolonged prothrombin time, which may complicate management of
      anticoagulant therapy. OBJECTIVES: To determine the validity of the INR as a
      monitor for warfarin therapy in patients with lupus anticoagulants and to
      investigate alternate approaches to monitoring warfarin therapy in these
      patients. DESIGN: Prospective case series. SETTING: Tertiary care hospital.
      PATIENTS: 34 patients with lupus anticoagulants. MEASUREMENTS: Prothrombin times
      were determined by using several thromboplastins, and INRs were calculated for
      the patients receiving warfarin. Factor II levels, chromogenic factor X levels,
      and prothrombin-proconvertin times were determined for patients receiving
      warfarin. RESULTS: For patients with lupus anticoagulants who were not receiving
      warfarin, prothrombin times were often elevated and varied significantly with
      different thromboplastins. Individual thromboplastins differed in sensitivity to
      the presence of a lupus anticoagulant. For patients receiving warfarin, INRs
      obtained by using different thromboplastins greatly varied and often
      overestimated the extent of anticoagulation. Chromogenic factor X levels and
      prothrombin-proconvertin times correlated well with each other and with
      established therapeutic ranges. CONCLUSIONS: Lupus anticoagulants can influence
      prothrombin times and lead to INRs that do not accurately reflect the true level
      of anticoagulation. Use of the INR to standardize prothrombin times is invalid
      for some patients with lupus anticoagulants. To prevent supratherapeutic or
      subtherapeutic anticoagulation, these patients must be individually monitored
      with a test that is insensitive to lupus anticoagulants.

PMID- 9245223
TI  - Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma.
AB  - BACKGROUND: Interleukin-6 has important lymphoid bioregulatory effects, and serum
      levels of interleukin-6 are often elevated in patients with lymphoma. OBJECTIVE:
      To determine the relation between serum levels of interleukin-6 before treatment
      and outcome in patients with diffuse large-cell lymphoma. DESIGN: Retrospective
      cohort analysis with multivariate analysis. SETTING: Tertiary referral center.
      PARTICIPANTS: 118 untreated patients with diffuse large-cell lymphoma who were
      enrolled in frontline chemotherapy protocols and 45 healthy controls.
      MEASUREMENTS: Serum levels of interleukin-6 were measured by using a sensitive
      enzyme-linked immunosorbent assay. Levels below the upper limit of the range for
      controls were considered normal. Outcomes were complete response, failure-free
      survival, and overall survival. RESULTS: Serum levels of interleukin-6 were
      higher in patients with lymphoma (median, 4.6 pg/ml [range, undetectable to 224
      pg/mL]) than in controls (median, undetectable [range, undetectable to 4.3
      pg/mL]) (P = 0.009). The complete response rate was 95% for persons with normal
      interleukin-6 levels and 55% for persons with high interleukin-6 levels (P =
      0.001). Patients with high interleukin-6 levels had inferior failure-free and
      overall survival rates (P < 0.001 for both comparisons). The actuarial 4-year
      failure-free and overall survival rates were 72% and 85%, respectively, for
      persons with normal interleukin-6 levels and 37% and 46%, respectively, for
      persons with high interleukin-6 levels. In multivariate analysis, interleukin-6
      was selected as the most significant predictor of complete response and failure
      free survival. Failure-free and overall survival of patients stratified according
      to International Prognostic Index score could be further stratified by
      interleukin-6 level (P < or = 0.03 for all comparisons). CONCLUSION: In patients
      with diffuse large-cell lymphoma, serum interleukin-6 levels are an independent
      prognostic factor for complete response and failure-free survival.

PMID- 9245224
TI  - Outcomes and cost-effectiveness of initiating dialysis and continuing aggressive
      care in seriously ill hospitalized adults. SUPPORT Investigators. Study to
      Understand Prognoses and Preferences for Outcomes and Risks of Treatments.
AB  - BACKGROUND: Renal failure requiring dialysis in the setting of hospitalization
      for serious illness is a poor prognostic sign, and dialysis and aggressive care
      are sometimes withheld. OBJECTIVE: To evaluate the clinical outcomes and cost
      effectiveness of initiating dialysis and continuing aggressive care for seriously
      ill hospitalized patients. DESIGN: Prospective cohort study and cost
      effectiveness analysis. SETTING: Five geographically diverse teaching hospitals.
      PATIENTS: 490 patients (median age, 61 years; 58% women) enrolled in the Study to
      Understand Prognoses and Preferences for Outcomes and Risks of Treatments
      (SUPPORT) in whom dialysis was initiated. MEASUREMENTS: Survival, functional
      status, quality of life, and health care costs. Life expectancy was estimated by
      extrapolating survival data (up to 4.4 years of follow-up) using a declining
      exponential function. Utilities (quality-of-life weights) were estimated by using
      time-tradeoff questions. Costs were based on data from SUPPORT and published
      Medicare data. RESULTS: Median duration of survival was 32 days, and only 27% of
      patients were alive after 5 months. Survivors reported a median of one dependency
      in activities of daily living, and 62% rated their quality of life as "good" or
      better. Overall, the estimated cost per quality-adjusted life-year saved by
      initiating dialysis and continuing aggressive care rather than withholding
      dialysis and allowing death to occur was $128,200. For the 103 patients in the
      worst prognostic category, the estimated cost per quality-adjusted life-year was
      $274,100; for the 94 patients in the best prognostic category, the cost per
      quality-adjusted life-year was $61,900. CONCLUSIONS: For the few patients who
      survived, clinical outcomes were fairly good. With the exception of patients with
      the best prognoses, however, the cost-effectiveness of initiating dialysis and
      continuing aggressive care far exceeded $50,000 per quality-adjusted life-year, a
      commonly cited threshold for cost-effective care.

PMID- 9245225
TI  - Gains in bone mineral density with resolution of vitamin D intoxication.
AB  - BACKGROUND: Vitamin D intoxication is associated with the mobilization of
      skeletal calcium. OBJECTIVE: To ascertain how the resolution of vitamin D
      intoxication affects bone density. DESIGN: Case series. SETTING: Referral service
      for metabolic bone disease in a tertiary care teaching hospital. PATIENTS: Four
      patients with osteoporosis who were each using several nonprescription dietary
      supplements and were found to have fasting hypercalciuria. INTERVENTION:
      Discontinuation of use of dietary supplements. MEASUREMENTS: Serial measurement
      of serum levels of 25-hydroxyvitamin D, ratio of fasting urinary calcium to
      creatinine, and bone mineral density for 3 years. RESULTS: Discontinuation of use
      of dietary supplements resulted in the normalization of serum levels of 25
      hydroxyvitamin D, the normalization of the ratio of urinary calcium to
      creatinine, and a mean annual increase in bone mineral density (+/- SD) of 1.9%
      +/- 0.5%. CONCLUSIONS: Occult vitamin D intoxication was detected in patients who
      were using dietary supplements that contained an unadvertised high level of
      vitamin D. Resolution of vitamin D intoxication was associated with a rebound in
      bone mineral density.

PMID- 9245227
TI  - The relation between systematic reviews and practice guidelines.
AB  - Clinical practice guidelines have been developed to improve the process and
      outcomes of health care and to optimize resource utilization. By addressing such
      issues as prevention, diagnosis, and treatment, they can aid in health care
      decision making at many levels. Several other decision aids are cast in the
      guideline lexicon, regardless of their focus, formulation, or format; this can
      foster misunderstanding of the term "guideline." Whether created or adapted
      locally or nationally, most guidelines are an amalgam of clinical experience,
      expert opinion, and research evidence. Approaches to practice guideline
      development vary widely. Given the resources required to identify all relevant
      primary studies, many guidelines rely on systematic reviews that were either
      previously published or created de novo by guideline developers. Systematic
      reviews can aid in guideline development because they involve searching for,
      selecting, critically appraising, and summarizing the results of primary
      research. The more rigorous the review methods used and the higher the quality of
      the primary research that is synthesized, the more evidence-based the practice
      guideline is likely to be. Summaries of relevant research incorporated into
      guideline documents can help to keep practitioners up to date with the
      literature. Systematic reviews have also been published on the dissemination and
      implementation strategies most likely to change clinician behavior and improve
      patient outcomes. These can be useful in more effectively translating research
      evidence into practice.

PMID- 9245226
TI  - Successful treatment of acquired hemophilia with oral immunosuppressive therapy.
AB  - BACKGROUND: Acquired autoantibodies to factor VIII in patients without hemophilia
      are rare, but they cause severe illness and death if not eradicated. OBJECTIVE:
      To examine daily therapy with oral cyclophosphamide and prednisone for acquired
      hemophilia. DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Nine
      consecutive patients without hemophilia who had severe hemorrhage caused by high
      titers of factor VIII inhibitors. INTERVENTIONS: Daily oral cyclophosphamide and
      prednisone. Coagulation factors were used only for bleeding. MEASUREMENTS: Plasma
      titers of factor VIII inhibitor, factor VIII activity, and clinical evidence of
      bleeding. RESULTS: All patients achieved complete remission, which was defined as
      loss of residual inhibitor activity and return to a normal titer of factor VIII.
      Therapy lasted a median of 12 weeks (range, 3 to 37 weeks). Bleeding resolved in
      a median of 3 weeks (range, 2 to 10 weeks). Median follow-up after
      discontinuation of therapy was 91 weeks (range, 61 to 164 weeks). CONCLUSION:
      Daily administration of oral cyclophosphamide and prednisone without empirical
      factor VIII therapy seems to be an effective and well-tolerated treatment for
      acquired hemophilia.

PMID- 9245228
TI  - Update in infectious diseases.

PMID- 9245229
TI  - Improving palliative care.
AB  - Although most deaths in the United States occur in hospitals, data suggest that
      hospitals and physicians are not equipped to handle the medical and psychosocial
      problems of dying patients. In this article, we review the barriers to achieving
      a peaceful death, including inadequate medical professional education on
      palliative care, and public and professional uncertainty about the difference
      between foregoing life-sustaining treatment and active euthanasia, and health
      professionals' difficulty recognizing when patients are dying and the associated
      sense that death is a professional failure. Other barriers include fiscal
      constraints on the length of stay, the number of nurses available to care for
      dying patients, legal and regulatory constraints on obtaining opioid
      prescriptions, and a segregated system of hospice care that requires patients to
      be separated from familiar health care providers and settings in order to receive
      palliative care at the end of life. Identifying the opportunities that can
      improve the delivery of palliative care at the end of life is the first step
      toward developing corrective approaches. Strategies that enhance these
      opportunities are proposed.

PMID- 9245230
TI  - Vitamin D supplementation: a word of caution.

PMID- 9245232
TI  - Blood sugar, disease, and nondisease.

PMID- 9245231
TI  - Experimental challenge of volunteers with malaria.

PMID- 9245233
TI  - What the book says.

PMID- 9245234
TI  - The dying experience.

PMID- 9245235
TI  - The dying experience.

PMID- 9245236
TI  - The dying experience.

PMID- 9245237
TI  - The dying experience.

PMID- 9245238
TI  - Management of Helicobacter pylori-positive patients with dyspepsia.

PMID- 9245239
TI  - What influences the frequency of angiography ... cardiologists?

PMID- 9245240
TI  - Insulin-like growth factor 1 therapy for type B insulin resistance.

PMID- 9245241
TI  - Isotretinoin in metastatic thyroid cancer.

PMID- 9245242
TI  - Regression of gastric lymphoma with therapy for Helicobacter pylori infection.

PMID- 9245243
TI  - Electroconvulsive therapy for status epilepticus.

PMID- 9245244
TI  - Temporal artery biopsy and corticosteroid treatment: changing conclusions without
      changing evidence.

PMID- 9245245
TI  - A serious threat to the medical chief residency.

PMID- 9245246
TI  - Cyfra 21-1 in monitoring cervical cancer: a comparison with tissue polypeptide
      antigen and squamous cell carcinoma antigen.
AB  - Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be
      related to tumor stage and tumour size in patients with cervical cancer and
      suggested to be a promising marker in squamous lung cancer. We compared the value
      of this new marker with tissue polypeptide antigen (TPA) and squamous cell
      carcinoma antigen (SCC-Ag) in monitoring 30 patients with squamous cell cervical
      cancer. Serum levels of each marker were studied in relation to tumour stage and
      clinical status of patient. The clinical performance of the various assays to
      separate those patients with complete remission from those patients with the
      presence of tumour (i.e., partial remission, stable disease, or progressive
      disease) was assessed by their receiver operating characteristic (ROC) curves. We
      found that tumour stage was a prognostic factor for survival (p = 0.02).
      Pretreatment serum Cyfra 21-1, TPA, and SCC-Ag levels were not related to stage
      of disease and were not found to be predictive of survival. In contrast, an
      elevated post-treatment serum SCC-Ag level was associated with a poor survival
      rate (p = 0.03). Such a relation was not found for Cyfra 21-1 or TPA. The
      clinical performance of post-treatment serum SCC-Ag levels in predicting the
      presence of tumour was better than the Cyfra 21-1 or TPA assays. This is shown by
      the left uppermost position of the ROC curve for SCC-Ag. We concluded that SCC-Ag
      appeared to be a better parameter than Cyfra 21-1 and TPA in predicting the
      presence of tumour during follow-up and survival of patients with cervical
      cancer.

PMID- 9245247
TI  - Male breast cancer: pathological and immunohistochemical features.
AB  - BACKGROUND: male breast cancer is uncommon and studies regarding the potential
      clinical relevance of the histopathological and immunohistochemical features are
      infrequently reported. MATERIALS AND METHODS: We investigated the biological
      characteristics of forty-one male patients with invasive breast cancer by
      assessing histopathological and multiple immunohistochemical features. RESULTS:
      The majority were no special type (ductal) (37/41), lobular cancer was not seen.
      73% were histological grade 3, 93% were positive for oestrogen receptor and 73%
      for progesterone receptor. The proportion of cancers positive for c-ebB-2 (45%),
      EGFR (20%), p53 (58%), MiB1 (40%), NCRC11 (78%), were similar to reports for
      female breast cancer. Nonsignificant associations between poor survival outcome
      and grade 3 tumours, and positive tissue staining for MiB1 and p53 were seen.
      CONCLUSION: While there ar similarities in the biological features of breast
      cancer in males and females, some differences were identified. Male breast cancer
      is more likely to be grade 3 tumours and hormone receptor positive.

PMID- 9245248
TI  - [Use of an anesthetic cream in the surgical treatment of phimosis].
AB  - The authors present their technique of local anaesthesia in the surgical
      treatment of phimosis using a cream composed of an eutectic mixture of lidocaine
      and prilocaine (Emla). This cream, unlike injectable local anaesthetics, allows
      surgical procedures to be performed on the prepuce without pain.

PMID- 9245249
TI  - [Granulocytic sarcoma of the testis without hematological manifestations].
AB  - A 30-year-old man with a testicular tumor ressembling a "round cell sarcoma" was
      treated for rhabdomyosarcoma. Complete remission was achieved but the patient
      relapsed and died of the disease. A retrospective diagnosis of granulocytic
      sarcoma was established using an anti-myeloperoxidase antibody, unfortunately not
      available at the time of the initial diagnosis. No hematological disorders were
      observed during the course of the disease. Four cases of granulocytic sarcoma of
      the testis have been reported in the literature. All these cases where
      accompanied or followed by leukemia. The present case seems to be the first case
      of granulocytic sarcoma of the testis not accompanied by hematological disorders.

PMID- 9245250
TI  - [Renovascular arterial hypertension: current aspects of physiopathology,
      diagnosis and treatment].
AB  - Renovascular hypertension is a potentially curable, secondary form of
      hypertension. It is caused by renal ischemic disease, which remains a significant
      clinical problem because of the increasing incidence of atherosclerosis with
      aging of the overall population. The role of the reinin-angiotensin system in
      renovascular hypertension has been consolidated by the discovery of angiotensin
      II receptor subtypes, various tissue renin-angiotensin systems and the function
      of angiotensin II as a vascular growth factor. To date renal vein renin
      estimation and converting enzyme renography seem to be the most reliable
      investigations to demonstrate the hypertensive role of a kidney before
      revascularization. Percutaneous transluminal angioplasty is a successful
      treatment in selected forms of renal artery stenosis. Open surgery consists of
      either bypass procedure or renal autotransplantation with extracorporeal
      reconstruction of the renal vasculature in cases of aneurysms or segmental renal
      artery stenoses. Control of hypertension and, increasingly important,
      preservation of renal function can be safely and successfully achieved, on the
      basis of careful diagnosis and individual selection of the therapeutic procedure
      are performed.

PMID- 9245251
TI  - [Retroperitoneal cystic lymphangioma in a child].
AB  - Cystic lymphangiomas are rare, benign tumors, which are mainly located in the
      neck or axilla. The fourteenth reported case in the literature of a pediatric
      retroperitoneal cystic lymphangioma is described. Symptoms, diagnostic procedure
      and therapy are reported and discussed.

PMID- 9245252
TI  - [Epidemiology of urinary lithiasis].
AB  - The objective of this study was to analyse the epidemiological profile of urinary
      stones based on one thousand cases observed in our institution over a 10-year
      period. The mean age of the patients was 45 years and two-thirds of patients were
      males. The kidney was the commonest site of stones, in 57.8% of cases. The stone
      was radiopaque in 86.4% of cases and was a staghorn calculus in 12.2% of cases.
      An associated renal malformation was observed in 10.4% of cases. Urinary stones
      is therefore a common disease, essentially observed in a young population and
      characterized by recurrence. It therefore constitutes a public health problem and
      prevention consists of detecting recurrences and treating stone-inducing factors.

PMID- 9245253
TI  - [Urolithiasis in children in West Algeria].
AB  - We analyzed a series of 61 stones from children aged 3 to 14 years old using
      Fourier transform infrared spectroscopy. The calculi were collected from urology
      departments of the University Hospitals of Oran, Sidi-Bel-Abbes and Mostaganem in
      West Algeria. This series is the first investigation concerning the composition
      of stones in children based on infrared analysis. Calculi were more frequent in
      males (75.4%) and mainly localized in the bladder (55.8%). Upper urinary tract
      calculi were more frequent in children over the age of 10 years, and the sex
      ratio was about 1. Calcium oxalate monohydrate was present in 70.5% of stones and
      was the main component in 50.8% of cases both in whole stones and nuclei. In
      contrast, calcium oxalate dihydrate was the main component in only 9.8% of
      calculi although it was present in 75.4% of stones. Ammonium urate was detected
      in 29.5% of stones and was always the main component of nuclei. Uric acid,
      observed in 31.1% of calculi, was the major constituent in 14.7% of stones and
      19.7% of nuclei. Magnesium ammonium phosphate was observed in 24.6% of stones as
      a consequence of urinary tract infection by urea-splitting bacteria. Our
      observations emphasized that the anatomical location of stone and their
      composition were in accordance with those previously reported in other countries.

PMID- 9245254
TI  - [Role of ureteroscopy in the treatment of lithiasis of the pelvic ureter. Apropos
      of 52 cases].
AB  - Between July 1990 and December 1995, 52 patients with lower ureteral calculi were
      treated by rigid ureteroscopy in the "B" Urology department of Avicenne Hospital.
      The use of ureteroscopy facilitated Dormia extraction (58%) or ultrasonic
      lithotripsy fragmentation (17%) or removal of the stone with the two procedures
      (21%). The overall success rate was 92.3% with a 2% retreatment rate.
      Complications were rare (3 of 52: 5.8 percent). The mean hospital stay was 3.3
      days. Based on our findings, we conclude that rigid ureteroscopy for lower
      ureteral stone removal is effective with low morbidity and shorter hospital stay.

PMID- 9245255
TI  - [Significance of the detection of fimbriae protein type adhesins on bacteria
      isolated in acute pyelonephritis in children].
AB  - A prospective bacteriological study in 50 children with acute pyelonephritis
      (APN) (32 girls and 18 boys) and 132 children with lower urinary tract infections
      (LUTI) (89 girls and 43 boys) was conducted from May to December 1993. Infection
      was defined by Kass' criteria and APN was defined by the clinical findings. C
      Reactive Protein (CRP) assay and postcontrast computed tomography in the presence
      of a doubt concerning the diagnosis. Escherichia coli (EC) was the bacterial
      species most frequently isolated (76%). A systematic search for fimbriae protein
      adhesins (group PAP: pyelonephritis associated pil) on the EC was performed by
      haemagglutination (human group A red blood cells). 64% of EC possessed fimbriae
      protein adhesions in the APN group versus only 20% in the LUTI group. In children
      in whom an organic abnormality was demonstrated, the incidence of fimbriae
      protein-positive EC was 33% while in children with no organic abnormality,
      particularly without reflux, 89% of EC presented fimbriae protein. A
      statistically significant difference was demonstrated between these two groups (p
      < 0.01). The results of this study illustrate the important role of these
      adhesins in the development of APN. These adhesins facilitate countercurrent
      ascension of bacteria in the ureter towards the upper urinary tract and can make
      the bacteria resistant to certain antibiotics. Testing for fimbriae protein can
      be useful in clinical practice when investigating the aetiology of APN in the
      absence of demonstrated reflux. A latex test should soon be available to
      facilitate the detection of fimbriae protein.

PMID- 9245256
TI  - [Seminal vesicle cyst associated with homolateral renal agenesis and megaureter.
      Apropos of a case].
AB  - We report a case of a 24-year-old male patient with cystic dilatation of the
      seminal vesicle associated with renal agenesis and megaureter. This patient
      complained of left renal colic with pollakiuria. We performed intravenous
      urography and ultrasound showed a cyst in the seminal vesicle associated with
      left megaureter and right renal agenesis. Treatment consisted of resection of the
      cyst and reimplantation of the left ureter into the bladder. No postoperative
      complications were observed. This association is rare and can be explained by the
      common embryological origin of the seminal vesicle and kidney and ureter. Its
      diagnosis is now facilitated by ultrasound and CT. The treatment of this tumor is
      surgical only when the lesions are responsible for clinical symptoms.

PMID- 9245258
TI  - The novel oxidoreductase KDRF (KM-102-derived reductase-like factor) is identical
      with human thioredoxin reductase.

PMID- 9245257
TI  - Three spinach leaf nitrate reductase-3-hydroxy-3-methylglutaryl-CoA reductase
      kinases that are regulated by reversible phosphorylation and/or Ca2+ ions.
AB  - In spinach (Spinacea oleracea L.) leaf extracts, three protein kinases (PKI, PKII
      and PKIII) were identified each of which phosphorylated spinach nitrate reductase
      on serine-543, and inactivated the enzyme in the presence of nitrate reductase
      inhibitor, 14-3-3. PKIII was also very active in phosphorylating and inactivating
      Arabidopsis (Landsberg erecta) 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1
      (HMGR1). PKI and PKII phosphorylated HMGR1 more slowly than PKIII, compared with
      their relative rates of phosphorylation of nitrate reductase. HMGR1 identical
      with those that are seen after phosphorylation of serine-577 by the sucrose non
      fermenting (SNF1)-like PK, 3-hydroxy-3-methylglutaryl-Co A reductase kinase A
      (HRK-A), from cauliflower [Dale, Arro, Becerra, Morrice, Boronat, Hardie and
      Ferrer (1995) Eur. J. Biochem. 233, 506-513]. PKI was Ca2+-dependent when
      prepared in the absence of protein phosphatase (PP) inhibitors, and largely Ca2+
      dependent when prepared in the presence of PP inhibitors (NaF and EGTA). The Ca2+
      independent portion of PKI was inactivated by either PP2A or PP2C, while the Ca2+
      dependent portion of PKI became increasingly activated during storage, which we
      presume was mimicking the effect of an unidentified PP. These findings indicate
      that PK1 is regulated by two functionally distinct phosphorylations. PKI had a
      molecular mass of 45 kDa on gel filtration and was active towards substrate
      peptides that terminated at the +2 residue from the phosphorylation site, whereas
      PKIII was inactive towards these peptides. PKII was Ca2+-stimulated under all
      conditions tested. PKIII was Ca2+-indepdented, inactivated by PP2A or PP2C, had a
      requirement for a hydrophobic residue in the +4 position of peptide substrates,
      had a molecular mass by gel filtration of approximately 140 kDa, and an antibody
      against the rye SNF1-related PK (RKIN1) recognized a 58 kDa subunit in fractions
      containing PKIII. These properties of PKIII are identical with those reported
      previously for the SNF1-like enzyme, HRK-A. Our results indicate a considerable
      complexity of kinase cascades mediating the regulation of assimilatory and
      biosynthetic pathways in response to environmental stimuli in plants.

PMID- 9245260
TI  - Adolescents who offend
AB  - No abstract

PMID- 9245259
TI  - [Go out and make all the people to be my patients. Happy pills one more time!].

PMID- 9245261
TI  - Family and social contexts of adolescent re-offenders
AB  - Drawn from a representative sample, 74 young people (15-16-years-old on average)
      who were being arrested frequently by the police ("re-offenders") were traced and
      interviewed wherever they were living about aspects of their family and social
      lives. Interview data revealed high levels of family disruption and a wide
      variety of current and past living circumstances. Interviewees reported good
      relationships with their mothers and strong social ties with friends and peers.
      Few were involved in any constructive day to day activities, a third claiming to
      be unemployed and most doing nothing. Drug and alcohol use were widespread and
      heavy, and there was evidence of many attempts to get help for a variety of
      problems-half had had some sort of psychological intervention or counselling
      arranged for them-and distress, general stresses and lack of support were not
      uncommon. Intervention and policy impliIcations are discussed.

PMID- 9245262
TI  - Adolescents who murder
AB  - Although few in number, children and adolescents who murder attract much public
      attention. Following a review of the literature on aetiology, assessment,
      treatment programmes and outcomes, descriptive data on a 5-year cohort of 20
      adolescent murderers from England and Wales are presented. An outline is made of
      their pathway through the care and criminal justice system together with a
      framework for ongoing individual therapy. Suggestions are made about refinement
      of categories of juvenile homicide, and increased information sharing between
      child and adolescent and adult forensic specialists and the relevance of this
      group to the mainstream adolescent offenders.Crimes of violence of children
      differ little from place to place and from epoch to epoch. In Britain
      approximately the same number of juvenile murderers and future privy councillors
      are born each week. Anger, shock, grief and self righteousness often demand
      certain punishments but sanctions thus motivated cannot be said to have the
      efficacy of curative measures (Wilson, 1973).

PMID- 9245263
TI  - Psychological characteristics of juvenile alcohol and drug users
AB  - The purpose of this study was to investigate whether personality tests could
      differentiate between alcohol and drug users among juvenile offenders. The
      subjects were 108 Icelandic juvenile offenders who had been given conditional
      discharge. The Eysenck Personality Questionnaire (EPQ) and the Gough
      Socialisation Scale were administered to all subjects. The results indicate that
      the subjects who were classified as drug users or frequent alcohol users scored
      significantly lower than the other juveniles on the Gough Socialisation Scale and
      significantly higher on the EPQ lie scale.

PMID- 9245264
TI  - Multisystemic therapy: an effective violence prevention approach for serious
      juvenile offenders
AB  - This article provides an overview of a treatment approach, Multisystemic Therapy
      (MST), that has demonstrated long-term reductions in criminal activity and
      violence among youth at high-risk for perpetrating violence. Importantly, central
      aspects of MST are consistent with the recent public health agenda of violence
      prevention in the United States. Moreover, as demonstrated from the findings of
      controlled clinical trials evaluating MST with serious juvenile offenders, the
      viability of the public health approach is supported.

PMID- 9245265
TI  - Psychotherapy for delinquents?
AB  - The results of a psychotherapy consultation service for delinquents are
      presented. Based on the clinical material obtained from this programme, and a
      review of relevant delinquency and psychotherapy literature, a working model of
      individual psychotherapy related to attachment theory as it applies to this
      population is discussed. Developmental and existential difficulties that warrant
      resolution are included, as are issues with resistance and counter transference.

PMID- 9245266
TI  - Bullying among incarcerated young offenders: developing an interview schedule and
      some preliminary results
AB  - In the light of past research on bullying and victimization among school children
      (which is reviewed), questions to measure bullying and victimization among
      incarcerated young offenders are developed. On the basis of two pilot studies, it
      is concluded that the anonymous, group-administered, self-completed questionnaire
      has problems, and that more complete and valid data can be obtained by asking
      questions about bullying in the context of an individual interview. The
      preliminary results are based on a small sample (n=20) of incarcerated young male
      offenders in Ontario, Canada. They show that most residents (70%) were involved
      in bullying, several times a week or more often, either as bullies (45%) or
      victims (25%). Larger-scale research on bullying among incarcerated young
      offenders is recommended, using individual interviews, and key issues to be
      addressed are set out.

PMID- 9245267
TI  - The ISRD Study-self-report findings from N. Ireland

PMID- 9245269
TI  - "Why don't you do it properly?" Young women who self-injure
AB  - Analysis of interviews with four self-injuring young women suggests that the
      meaning of self-injury is not the same as the meaning of attempted suicide, and
      that the two acts are related in the sense that self-injury is an adaptive
      alternative to suicide. The function of self-injury as a communicative act and
      the extent to which self-injurers can control their actions are also discussed.
      It is suggested that, within the context of self-injury as survival, issues of
      communication and control do not have the significance that they are frequently
      supposed to have. Implications for clinical practice are discussed.

PMID- 9245268
TI  - Adolescent machine gambling and crime

PMID- 9245270
TI  - Psychological characteristics of juvenile alcohol and drug users
AB  - The purpose of this study was to investigate whether personality tests could
      differentiate between alcohol and drug users among juvenile offenders. The
      subjects were 108 Icelandic juvenile offenders who had been given conditional
      discharge. The Eysenck Personality Questionnaire (EPQ) and the Gough
      Socialisation Scale were administered to all subjects. The results indicate that
      the subjects who were classified as drug users or frequent alcohol users scored
      significantly lower than the other juveniles on the Gough Socialisation Scale and
      significantly higher on the EPQ lie scale.

PMID- 9245271
TI  - Staff looking after children in local authority residential units: the interface
      with child mental health professionals
AB  - Seventy-two members of staff working in children's residential units in a Local
      Authority were surveyed, to elicit their experiences and evaluations of working
      with child mental health professionals. Whilst the majority of staff held few or
      no formal educational qualifications, they emerged as an experienced group, with
      a level of confidence in their knowledge and skill base. Support was identified
      as coming predominantly from within units themselves; relatively few staff had
      direct contact with child psychiatrists or psychologists, although many children
      received a service. Staff in general felt that child mental health services were
      not helpful to them in terms of their work with young people. However, the
      majority of staff indicated a need for greater direct involvement across a range
      of child behavioural and emotional problems. The findings are discussed in terms
      of the changing population of "looked after" children and the recommendations of
      the Warner Report.

PMID- 9245272
TI  - Ego-identity status and narrative structure in retrospective accounts of parental
      career influence
AB  - In this paper, the relationship between identity status categories and the
      experience of parental influence on career development is examined. The life
      stories of 11 young adults regarding significant events through which their
      parents influenced them were classified by narrative structure based on Gergen
      and Gergen's macrostructure framework. The resulting narrative types were then
      assessed in terms of their relationship to each participant's score on the
      Extended Objective Measure of Ego-Identity Status. Both observational
      associations and Fisher's Exact Tests of Probabilities suggest a relationship.
      Results indicated that narratives of parental influence on career development may
      be reflective of one's stage of identity formation, that is, to one's progress in
      exploring and committing to career values and goals.

PMID- 9245273
TI  - Symptoms of affective disorder in pre-adolescent vs. adolescent inpatients
AB  - This study is a comparison of symptoms between depressed inpatient pre
      adolescents and adolescents. One hundred and eight hospital records were reviewed
      with a structured format and were assigned DSM-III-R (American Psychiatric
      Association, 1987) diagnoses. Twenty-two pre-adolescents and 34 adolescents had
      symptoms documented which satisfied criteria for major depression. These two
      groups were compared on demographic and symptom variables. The majority of
      variables studied did not differ between age groups. Of those which did, the most
      predictive of adolescence were melancholia, global improvement rating, and
      suicide attempts. Temper outbursts, distractibility, and irritability predicted
      the prepubertal age group.

PMID- 9245274
TI  - Self-image, the smoker stereotype and cigarette smoking: developmental patterns
      from fifth through eighth grade
AB  - In the present study the role of self-consistency and self-enhancement
      motivations in adolescent cigarette smoking was examined. Respondents were 1971
      fifth through eighth graders. They were asked to provide information about the
      number of cigarettes they had smoked in their lifetime and to rate themselves and
      most smokers on nine dimensions tapping coolness, sociability and intelligence.
      The results revealed that similarity between the self-image and smoker stereotype
      increases with age. In addition, evidence for self-consistency motivations for
      smoking was obtained on all three traits and support for self-enhancement
      motivations emerged for the cool trait. Finally, it was found that self
      consistency becomes increasingly important from fifth to eighth grade. This is
      the first empirical demonstration of developmental differences in the relation
      between the self-image, the smoker stereotype and smoking. The importance of the
      self-identification process in adolescent smoking is discussed.

PMID- 9245276
TI  - Adolescent machine gambling and crime
AB  - There is growing evidence that children and adolescents who gamble excessively on
      fruit machines may engage themselves in stealing and commit other criminal
      offences to fund their habit yet there has been little evidence from the legal
      professions themselves. The aim of the survey conducted was to see if there was
      any relationship between criminal activity (most notably theft) and gaming
      machine use. During a 1-year period, police officers in Plymouth (South West
      England) collected information from 1851 juvenile offenders with whom they came
      into contact. The results revealed approximately 4% of juvenile crime was
      associated with gaming machine use and the survey offers evidence that a minority
      of individuals commit crimes in order to supplement their fruit machine playing.

PMID- 9245277
TI  - Young people and mentoring-towards a typology?
AB  - This study explores young people's perceptions of mentoring relationships and
      proposes a typology of mentoring forms. A sample of 150 adolescents was
      interviewed both in groups (n=12 groups of up to 13 young people) and
      individually (n=30 individuals recruited from the group interviews). Results
      suggested that a range of forms of mentoring were perceived as valuable by
      different groups of young people and from these a typology of mentoring forms is
      devised.

PMID- 9245278
TI  - Identity, regression and development
AB  - Regression has held varied meanings within psychoanalytic and developmental
      literatures. Within psychodynamic literature, regression has often implied return
      to earlier developmental levels for the purpose of mastering childhood trauma. It
      has, however, been stated that regression is an essential and adaptive feature of
      normative adolescent development. Within developmental literature, regression has
      been discussed in relation to structural characteristics of stage change; the
      concept has remained problematic, for developmental theories often postulate
      directionality in development inconsistent with the notion of regression. It is
      the purpose of this paper to (a) review varied meanings regression has held
      within psychoanalytic and developmental literatures, (b) focus on the forms,
      frequencies and functions of regression when examining data from two structural
      developmental models addressing dimensions of normative adolescent identity
      development, and (c) consider precipitants for different forms of regressive
      movement. The paper will conclude with suggestions for hypotheses to be tested in
      future research.

PMID- 9245279
TI  - Validity of the Beck Depression Inventory, MMPI, and Rorschach in assessing
      adolescent depression
AB  - The purpose of the present study was to assess the validity of the Beck
      Depression Inventory (BDI), the MMPI Depression scale (MMPI-D), and the Rorschach
      Depression Index (DEPI) in measuring adolescent depression. Retroactive charts of
      118 hospitalized adolescents were divided into depressed (n=66) and nondepressed
      (n=52) groups, based on the psychiatric diagnosis. Results indicated significant
      differences between the means of the two groups on the BDI (p<0.00001) and the
      MMPI-D scale (p<0.0001), establishing concurrent validity for these measures of
      depression. Correlation coefficients among the three measures of depression
      indicated a significant relationship between the BDI and the MMPI-D scale
      (p<0.01), again supporting the concurrent validity of these instruments.
      Predictive utility was determined for each of the three instruments individually
      and in combination, with results indicating that the BDI and MMPI-D scales alone
      and in combination significantly discriminated depressed from nondepressed
      adolescents. The MMPI-D scale alone was the most accurate measure in classifying
      the participants into their respective groups. The DEPI was not established as a
      valid predictor of adolescent depression.

PMID- 9245280
TI  - Self-esteem and mental health in early adolescence: development and gender
      differences
AB  - A longitudinal study of a general population (n=219; M age: 12, 13 and 14), was
      carried out between 1990 and 1993 over 3 years in Lausanne (Switzerland). Several
      questionnaires, validated in French, were used: Perceived Competence Scale,
      Social Support Appraisal and a questionnaire on mental health developed in our
      research Unit. We attempted to answer the following questions: Is there a global
      change in self-esteem during early adolescence? If so, does the way in which the
      young person perceives himself vary according to the social and relational
      environment? What are the differences between boys and girls in the development
      of self-esteem? What is the relation between self-esteem and mental health?As to
      the specific differences according to gender, results show that girls tend to
      have a poorer self-esteem than boys, whatever the domains taken into
      consideration. Differences are more significant with reference to appearance and
      athletic performance. As far as the development of self-esteem is concerned,
      there is no major change, notably when considering global perception. Results of
      a factor analysis underscore the fact that girls' self-esteem is more global and
      less differentiated by domain while boys separate the scholastic and behavioral
      part of their experience from the social. Global self-esteem has more influence
      on the level of depressive mood in girls than in boys.

PMID- 9245281
TI  - Identity formation and religious orientation among high school students from the
      United States and Canada
AB  - Two studies were conducted to examine the relations between Marcia's four
      identity statuses and Allport and Ross' four religious orientations. Study 1 was
      conducted among 38 Mormon and 47 non-Mormon high school students living in a
      predominantly Mormon Utah community. Study 2 was conducted among 102 Jewish high
      school students living in Ontario, Canada. It was revealed through the use of
      MANCOVA procedures that, in both studies, identity diffusion was associated with
      the extrinsic religious orientation. The indiscriminate proreligious scored
      significantly higher on foreclosure than the intrinsic and nonreligious groups,
      and the extrinsic scored significantly higher on moratorium than the intrinsic
      and nonreligious groups in Study 1. The indiscriminate proreligious scored
      significantly higher on identity achievement than those classified as extrinsic
      or nonreligious in Study 2. The indiscriminate proreligious and intrinsic
      religious orientations were associated with higher scores in three subscales of
      ethnic identity for the Jewish adolescents. Potential moderating influences of
      religious orthodoxy, religious attendance, grade, and gender were found to not
      operate between identity and religious orientation.

PMID- 9245282
TI  - Adolescent homicide: towards assessment of risk
AB  - Recent murders committed by children and adolescents have raised concern over the
      detection and management of dangerous youngsters in our society. Yet in the
      training of child and adolescent mental health professionals the assessment and
      management of dangerousness to others is frequently given little attention. This
      paper attempts to begin to redress the balance by reviewing the mental health
      literature relevant to homicidal children and adolescents. Background and
      situational factors relevant to risk are described. Background factors include
      the witnessing of serious violence, both live and on the screen, as well as abuse
      through neglect and deprivation. Such trauma can assist in the creation of a
      morbid identity and a cognitive set that make murder possible in certain
      situations. Other background factors include learning difficulties and problems
      with impulse control. However even if a youngster is assessed as highly dangerous
      it is frequently difficult in the current climate to offer adequate intervention.
      Issues in the prevention of violence are considered.Through abuse my emotions and
      self-respect were murdered and so I no longer cared. Do people stand trial for
      killing someone's insides? No, because you can't produce a corpse... (a teenage
      killer).

PMID- 9245283
TI  - Who has the final say? Decisions on adolescent behaviour within the family
AB  - The transition to adolescence involves significant changes for the family. To
      date, research on these changes and how they occur has been restricted by lack of
      suitable measures. An instrument-the Perspectives on Adolescent Decision-Making
      Questionnaire-was designed for such research. It examines 21 issues which can
      lead to conflict. The instrument was completed by 500 Italian adolescents aged 13
      and 15. Sensitivity to age and sex differences was examined, and perceptions of
      personal choice, parental feelings, conflict and normal patterns for adolescents
      were analysed. The instrument offers promising possibilities for more effective
      study of parent/offspring relationships during the adolescent period.

PMID- 9245284
TI  - Outlook on life: how adolescents and children view the life-style of parents,
      adults and self
AB  - A new Outlook on Life measure was constructed to identify how adolescents and
      children see their lives. Three scales were formed and named the View of Parents,
      View of Adults and View of Self scales. The three scales were found to correlate
      highly with subjects' emotional state: the more positive views they had of their
      parents, adults and their own life, the less depressed they felt.

PMID- 9245285
TI  - Adolescent focal theories: age-trends in developmental transitions
AB  - Focal theory is considered as a framework for looking at psychosocial and leisure
      transitions in middle and later adolescence. Although these transitions are
      examined from a different perspective in the present study, by utilising cross
      sectional survey data from a representative sample of three age groups of young
      Scots (13-14, 15-16 and 17-18 year-olds), the results confirm and extend the
      general age-trends in relational issues and leisure involvement reported in
      original studies. Within this overall picture, few gender differences are found
      in age-related relational transitions, but gender differences are apparent in
      shifting focuses of leisure involvement with age. Further, the findings suggest a
      linkage between relational issues in adolescence and leisure contexts, where
      psychosocial processes are seen to be associated with contextual changes in young
      people's lives. Focal theory has been criticised for a failure to take true
      account of the social circumstances, constraints and contexts affecting
      adolescent development, but in the present study surprisingly few differences are
      found with respect to the young person's social class of family background, for
      example, with age-trends in developmental transitions similar for all social
      groups. By contrast, in later adolescence aspects of the young person's own socio
      economic position, rather than that of their family background, are clearly
      linked to both relational issues and leisure involvement, for example, creating a
      disrupting effect on those young people who are currently unemployed or non
      employed at this age.

PMID- 9245286
TI  - The rules of the game: teenagers communicating about sex
AB  - The present study examined the rules used by 16-year-olds (n=191) to guide their
      behaviours during a sexual encounter. Boys and girls were asked about social
      rules for giving messages indicating that they did or did not wish to have sex,
      and strategies for encouraging or avoiding sex, together with the acceptability
      and usefulness of these strategies. They were also asked if they had used any of
      the strategies. A variety of rules were endorsed and young people found it easier
      to encourage than to discourage sex. There were few differences between boys and
      girls in their understanding of the rules but the relationships between
      acceptability, usefulness and actual use of a strategy varied according to
      gender. For the avoidance strategies the relationships were moderate but stronger
      for girls, whereas patterns of relationships were strong across all encouragement
      strategies and equally so for boys and girls. The findings are discussed in the
      context of divergence between these young people's rhetoric of equality and their
      lived reality.

PMID- 9245287
TI  - Bulimia and the diffusion status of ego identity formation: similarities of the
      empirical descriptors of self and parent
AB  - A comparison was made between the empirical literature describing the
      characteristics of bulimic adolescents and the empirical literature describing
      adolescents in the various identity statuses within Erikson/Marcia's stage/status
      theory. A pattern of similarities emerged. Bulimics and diffused persons have
      been described as having personal characteristics and familial descriptors which
      are similar. No comparable similarities were found for the other well researched
      transitional statuses, that is, moratorium, foreclosure, or achievement. Present
      theories of bulimia suggest that a disruption in the second individuation occurs.
      However, none have attempted to operationalize the disruption in the adolescent
      individuation in terms of the transitional status. The comparison of two
      empirical literatures leads to a number of testable hypotheses that may advance
      the understanding of bulimia.

PMID- 9245288
TI  - Communication patterns and alliances between parents and adolescents during a
      structured problem-solving task
AB  - The influence of gender on communication patterns and reciprocal alliances was
      observed within the context of a controlled problem-solving task. Participants
      included 20 adolescent boys and 20 adolescent girls with their parents. The study
      found that families with boys engaged in more active bargaining than families
      with girls. Sons made offers for alliances to mothers at almost twice the rate of
      daughters. Also, adolescent gender may influence communication between mothers
      and fathers. Mothers seem particularly influenced by the gender of their
      adolescent, and adolescents appear to be influenced by whether they are
      interacting with their mother or father.

PMID- 9245289
TI  - Assessing adolescent problems: an overview of the adolescent problems inventory
AB  - The Adolescent Problems Inventory (API) and the Problem Inventory for Adolescent
      Girls (PIAG) are commonly employed in studies of antisocial and delinquent
      behaviour. This paper offers a review and critique of these inventories. The
      development and construction of the inventories are detailed, followed by
      discussion of their psychometric properties. The weight of evidence suggests that
      the inventories are related to behavioural indices associated with antisocial and
      delinquent behaviour. More recent studies have considered the factor structure of
      the API, suggesting several dimensions of social functioning. It is concluded
      that the API and PIAG are robust instruments that can yield valuable clinical and
      research data.

PMID- 9245290
TI  - Job search strategies, attitudes to school and attributions about unemployment
AB  - Two-hundred and seventy British final-year school-leavers completed a
      questionnaire battery looking at attitudes to school, attributions for
      unemployment, job search strategies and the perceived characteristics of an ideal
      job. Six varimax-rotated factor analyses were performed on each part of the six
      part questionnaire. In accordance with similar studies in the area, each of the
      questionnaire sections yielded a predictable factor structure. Higher-order
      factor analysis showed five clear factors, which together accounted for nearly
      45% of the variance. They were labelled: self-effort strategies, fatalistic,
      background, extrinsic and alienated. This showed that job search strategies,
      career advice, employment attributions and the perceived most and least desirable
      features of jobs are clearly interrelated. The complexity and interrelatedness of
      these cognitions about work suggest they may be difficult to change.

PMID- 9245291
TI  - Culture and problem behaviors among inner-city African-American youth: further
      explorations
AB  - The present study examined connections between culture and problem behaviors
      among 119 inner-city African-American fifth and sixth graders. The relevant
      orientations of the Afrocultural, Anglocultural and marginalized minority realms
      of the African-American experience were considered in terms of mean endorsement,
      interrelationships, and relationships with aggressive and delinquent behaviors.
      Results indicated that youth endorsed the Afrocultural orientation of
      spirituality and the Anglocultural orientation of effort optimism most highly.
      Afrocultural orientations were positively associated with effort optimism, while
      the other Anglocultural orientations correlated positively with marginalized
      minority orientations. The Anglocultural orientation of person/object relations
      and the marginalized orientations of school rejection, and gang-related activity
      predicted problem behaviors. The Afrocultural orientations did not emerge as
      significant negative predictors of such behaviors. Findings are discussed
      primarily in terms of directions for future research.

PMID- 9245293
TI  - Introduction: Identity development in context

PMID- 9245292
TI  - Expectations and judgments regarding bystanders&raquo; and victims&laquo;
      responses to peer aggression among early adolescents
AB  - The purpose of the current research was to investigate early adolescents'
      thinking about peer behaviors when associates engage in acts of aggression. The
      participants (n=195), 4th, 6th, and 8th graders, received two sets of questions.
      One set pertained to evaluations of bystanders' expected and prescribed
      behavioral responses when the relationship of the bystander to the perpetrator
      and to the victim was manipulated. That is, the perpetrator and the victim were
      either good friends or acquaintances of the bystander. A second set pertained to
      evaluations of victims' expected and prescribed behavioral responses when the
      perpetrator was either a good friend or an acquaintance. The overall findings
      suggest that evaluation of behavioral responses on the part of bystanders and
      victims is influenced by the relationship among the parties involved. Grade
      differences are noted.

PMID- 9245294
TI  - Identity as adaptation to social, cultural, and historical context 
AB  - Adaptation may be the best way to conceptualize the complex, multilateral
      relationship between individual identity and sociocultural context, because it
      recognizes the causal importance of culture yet also recognizes individual choice
      and change. This argument is developed by considering how several historical
      changes in the sociocultural context (i.e. increasing freedom of choice, changed
      interpersonal patterns, loss of traditional value bases, and rising tension
      between desire for uniqueness and difficulty of achieving it) have led to changes
      in the nature of identity. Although identity adapts to changes in its
      sociocultural context, these changes sometimes create new problems, including the
      specially problematic nature of modern selfhood.

PMID- 9245295
TI  - Sociological perspectives on identity formation: the culture-identity link and
      identity capital
AB  - This paper lays the groundwork for understanding identity formation in an
      interdisciplinary fashion by addressing the problem of how culture and identity
      are interrelated. I attempt to resolve this problem by framing the "culture
      identity link" with concepts representing three social-structural periods at
      three levels of analysis (the macro, micro, and psychological). The concept of
      "identity capital" is derived from this framework, depicting how individuals can
      negotiate life passages in an increasingly individualistic, complex and chaotic
      world. These formulations place existing research in a broad perspective and
      suggest avenues for future work.

PMID- 9245296
TI  - A developmental social psychology of identity: understanding the person-in
      context
AB  - This essay focuses on the socialization of identity formation. It provides a
      theory about the developmental social psychology of identity. A set of
      propositions are derived from the authors'reading, research, cultural
      observations and clinical experience regarding adolescent identity formation. The
      essay covers the socialization process, nature of the self, processes of growth
      and development, person-in-context, and a statement on the linkage between macro-
      and micro-environmental influences on identity. The theoretical propositions are
      offered for their potential heuristic utility in the study of identity formation
      during adolescence and young adulthood.

PMID- 9245297
TI  - Age differences in adolescent identity exploration and commitment in urban and
      rural environments
AB  - Sociocultural context may play an important role in identity development by
      shaping the opportunities adolescents are facing. To examine this, adolescents
      living in urban and rural environments were compared in terms of age differences
      in identity exploration and commitment. Younger (13-14-year-olds) and older (16
      17-year-olds) males and females from urban and rural areas in both Australia
      (n=367) and Finland (n=316) were investigated. The participants completed the
      Exploration and Commitment Questionnaire which includes items concerning future
      education, occupation and family. The results showed that the older youths living
      in Australian urban environments showed higher levels of exploration and
      commitment concerning both their future education and occupation than the younger
      ones, whereas there was an age-related decrease in these variables among
      adolescents living in Australian rural areas. No urban vs. rural differences were
      found for Finnish adolescents.

PMID- 9245298
TI  - Ethnic identity in aboriginal Sami adolescents: the impact of the family and the
      ethnic community context
AB  - The influence of parentage and ethnic community context on ethnic self
      identification and ethnic attitudes and behaviour were examined in 245 indigenous
      Sami adolescents in northern Norway. Ethnic identity was strongly related to both
      parentage and type of ethnic community. Monoethnic adolescents at the coast (with
      great integration and assimilation) identified themselves mostly as bicultural or
      Norwegian, but in the highland (with strong ethnic support), they identified
      strongly as Samis. Adolescents with mixed parentage identified strongly as
      Norwegian at the coast but mostly as bicultural in the highland. Ethnic behaviour
      and attitudes were significantly associated with both family and regional
      context; ethnic self-identification was related to other components of ethnic
      identity.

PMID- 9245299
TI  - Young, Black, and female: the challenge of weaving an identity
AB  - This is an exploratory qualitative study of the experience of identity in late
      adolescent African-American women. Using a semi-structured interview, 17 18- to
      22-year-old community college students were interviewed about how they see their
      identity and about the personal salience of various identity domains-race,
      gender, sexual orientation, relationships, career, religious beliefs, and
      political beliefs. It was found that these seven ego identity domains varied in
      importance, with racial identity as the most salient, while the domains of
      gender, relationships, and career were also important sources of identity. A
      sense of "strength" also emerged as an important element of self-definition.
      Particular attention is paid to the intersection of racial and gender identity
      for these African-American women who must evolve a sense of self within the
      context of a society that devalues Blacks and women.

PMID- 9245300
TI  - Events associated with identity status change
AB  - This study examines events associated with identity status change between late
      adolescence and mid-adulthood. One hundred adults, aged 40-63 years, participated
      in a retrospective study of identity development. An adaptation of Marcia's
      (1966) Identity Status Interview was used to examine identity status movements
      within five identity domains. For each identity transition, the event judged to
      be primarily responsible for precipitating change was coded as follows: "age
      graded," "history-graded," "critical," "family life cycle stage," "different
      milieu," "internal change," "influence of significant other," and "lack of
      opportunity". "Internal change" was associated with the greatest frequency of
      changes into achievement, moratorium, and diffusion statuses across most domains;
      "influence of a significant other" was most commonly associated with the
      transition to foreclosure in most domains. Few significant associations were
      found among identity status, event type, and demographic variables within each
      identity domain. Implications of these findings for our understanding of identity
      formation are briefly discussed.

PMID- 9245301
TI  - Commentary: Identity, context, and development

PMID- 9245302
TI  - Addiction-risk and aggressive/criminal behaviour in adolescence: influence of
      family, school and peers
AB  - In this study, data from 2814 15- and 16-year-old secondary school students were
      analysed to investigate the collective influence of family, school and peers on
      behavioural problems in adolescence. Adolescents with addiction-risk and/or
      aggressive/criminal behaviour were compared to those who did not display such
      behaviour. Adolescents with behavioural problems were characterized by having a
      more negative perception of the environment with regard to most of the variables
      related with family, school and peers. Clearly behavioural problems are
      associated with problems in multiple environments. Some differences were found
      between boys and girls: multiple regression analyses showed that for boys,
      problems at school were the most important predictor of behavioural problem
      scores, while for girls, this applied to problems at home.

PMID- 9245303
TI  - Ethnicity and adolescent deliberate self-harm
AB  - The characteristics of all adolescents referred to the psychiatric service of a
      tertiary hospital following an episode of deliberate self-harm (DSH) were
      studied. Of 100 adolescents selected over a 3-year period, 64 White and 28 Black
      adolescents were compared to identify factors associated with DSH in Black
      adolescents. The main findings were: (1) the referral rate for Black adolescents
      was in proportion to the community composition; (2) the characteristics of Black
      and White adolescents referred following DSH were similar for background socio
      demographic variables, psychiatric symptoms, circumstances of the attempt and
      outcome. However, more social stress was reported in the Black group.

PMID- 9245304
TI  - Deliberate self-harm in adolescents: hopelessness, depression, problems and
      problem-solving
AB  - This study looks at a group of adolescents who have taken overdoses and examines
      the type and severity of their problems. It measures hopelessness and depression,
      and whether these adolescents feel their parents understand them. The study also
      examines the ways in which these adolescents perceive their overdose as a problem
      solving mechanism.The study shows that hopelessness in adolescent self-harm is an
      important independent variable over and above the level of depression. The
      adolescents report a wide range of problems with severe and significant problems
      particularly in the area of family relationships and school.Finally, the paper
      postulates links between severity of problems, hopelessness and deficits in
      problem-solving abilities, and suggests areas for potential therapeutic
      interventions.

PMID- 9245305
TI  - Promoting cognitive and ego development of African-American rural youth: a
      program of deliberate psychological education
AB  - The purpose of this study was to investigate the effects of a role-taking, action
      learning program on the cognitive and ego development of African-American rural
      high school students. The program employed instruction in scientific problem
      solving in relation to past and current contributions of African-American
      scientists. There were two experimental and two comparison groups during the one
      semester program. The main effects were assessed in two related domains: (1)
      concrete to abstract thinking (a Piagetian measure); and (2) self-concept
      development (Loevinger's Ego Stages). The results indicated statistically
      significant gains in both abstract thinking and ego stage. Implications for
      school curriculum modification are also detailed.

PMID- 9245306
TI  - Teenage mothers and the adult mental health of their sons: evidence from a
      Stockholm cohort
AB  - Data from a Swedish male cohort born in 1953 is used to investigate the effects
      of teenage motherhood on later mental health and illness. Measures of coping
      ability and psychiatric impairment at the age of 19 years and of hospitalization
      with a psychiatric diagnosis at ages 20-30 show that the sons of teenage mothers
      have a poorer health record than those born to older women. The differences
      disappear, however, when controls are introduced for the marital and socio
      economic status of the boys' mothers, and the data suggest that teenage
      motherhood is not associated with poor outcomes in the absence of other
      predisposing factors.

PMID- 9245307
TI  - Family influences on self-reported delinquency among high school students
AB  - We investigated the links between perceived family relationships, parental
      discipline style, locus of control, self-esteem and self-reported delinquency
      among 177 Australian teenagers. The prediction that locus of control and self
      esteem would mediate the effects of family process on delinquency was tested
      using structural equation modelling. Although there appeared to be a good fit
      between the data and the proposed model, the amount of variance explained by the
      predictor variables was not large. Among females, the best predictor of low
      levels of self-reported delinquency was an inductive discipline style, whilst for
      males high levels of self-reported delinquency were best predicted by a punitive
      discipline style. Among males, positive family relations was a significant
      predictor of high self-esteem. No mediating effects of self-esteem and locus of
      control were observed. The findings are discussed with reference to previous
      research, and some implications for clinical practice are also noted.

PMID- 9245308
TI  - Self-concept and questions of life: identity development during late adolescence
AB  - The purpose of the present study was to explore identity development in late
      adolescent (18-20) years. Three areas were examined: (a) self-concept, (b)
      existential questions; content and communication patterns, and (c), connections
      between (a) and (b). The population consisted of 44 Swedish college students.
      Three methods were used: a questionnaire, the writing of a short essay and a self
      evaluation test, Structural Analysis of Social Behavior (SASB). The results
      demonstrated a positive and stable self-concept for the majority of the group,
      and that questions of life mainly concerned questions of future. The quality of
      the self-concept (positive vs. negative) was significantly related to how
      subjects experienced adults' interest in their existential questions. Several
      issues are discussed: the importance of the social environment for identity
      development not only during early childhood but also during adolescence, the use
      of the SASB method in this age group and the need for placing processes of
      integration into focus in research concerning late adolescence.

PMID- 9245309
TI  - Secrets and security: knowledge and the confinement of adolescents
AB  - Adolescents in a psychiatric unit may go through periods of crisis. This paper
      analyses crises occurring at a psychiatric adolescent unit over a period of 4
      months. These crises were found to have a circular pattern and each stage in the
      crisis connected demands for security with demands for the passage of
      information. Four patterns of crisis were identified, named as ambivalent,
      avoidant, chaotic and rigid. In each crisis the transferred information was found
      to be descriptive of the adolescent's relationship with adults important in his
      or her life. Each crisis could be understood as an attempt to change the
      adolescent's relationship with these adults.

PMID- 9245310
TI  - Investigation of Liquid Surface Rheology of Surfactant Solutions by Droplet Shape
      Oscillations: Experiments
AB  - The experimental results of droplet shape oscillations are reported and applied
      to the analysis of surface rheological properties of surfactant solutions. An
      acoustic levitation technique is used to suspend the test drop in air and excite
      it into quadrupole shape oscillations. The equilibrium surface tension, Gibbs
      elasticity, and surface dilatational viscosity are determined from the
      measurements of droplet static shape under different levitation sound pressure,
      oscillation frequency, and free damping constant. Aqueous solutions of sodium
      dodecyl sulfate, dodecyltrimethylammonium bromide, and n-octyl beta-d
      glucopyranoside are tested with this system. The concentrations of the solutions
      are below the critical micelle concentration. For these solutions it is found
      that the surface Gibbs elasticity approaches a maximum at a moderate
      concentration, and its value is less than that directly calculated from the state
      equation of a static liquid surface. The surface dilatational viscosity is found
      to be in a range around 0.1 cps.

PMID- 9245311
TI  - Hydrocarbon Drainage along Corners of Noncircular Capillaries
AB  - An approximate solution for liquid flow along corners of noncircular capillaries
      is proposed that relates the flow resistance to the geometry of a capillary and
      to the contact angle of the interfaces. The theory predicts liquid flow rates for
      both two-phase (hydrocarbon/air) and three-phase (hydrocarbon/air/water)
      drainage. This solution is found to be superior to other expressions in the
      literature. Drainage rates of two different hydrocarbons along corners of square
      capillaries are measured with both air and water as stationary phases. The new
      solution was used to predict the measured hydrocarbon drainage rates
      successfully. Comparison of the measured and predicted drainage rates indicates
      that a free boundary is appropriate for the air/hydrocarbon interface and a no
      flow boundary condition is valid for the water/hydrocarbon interface. The effect
      of spreading coefficient on drainage rates is also demonstrated by the
      measurements and is compared with the proposed solution. A brief discussion of
      three-phase relative permeabilities is offered based on the measured drainage
      rates and proposed solution.

PMID- 9245312
TI  - Elastic-Like and Viscous-Like Components of the Shear Viscosity for Nearly Hard
      Sphere, Brownian Suspensions
AB  - The shear properties of Brownian, rigid spheres consisting of sterically
      stabilized, crosslinked polymethylmethacrylate (PMMA) particles were studied in
      suspension. Three different volume fractions were used to carry out this study.
      The suspensions' elastic-like and viscous-like components of the shear stress
      were measured by a recently developed technique utilizing cessation of steady
      shear. The elastic-like viscosity component, or the amount of stress retained at
      the instant of cessation divided by the shear rate, due to Brownian and possible
      interparticle forces, decreased in magnitude over the entire range of shear rates
      used (shear thinning). The decay of the elastic-like stress with time after
      cessation of flow was also analysed and found to fit a power law relation. The
      viscous-like component, or the amount of stress lost at the instant of cessation
      divided by the shear rate, is related to hydrodynamic interactions between and
      drag on particles and remained essentially constant with shear rate. These data
      are the first of this kind gathered for a model hard sphere system (i.e.,
      mechanical means) and agrees well with results of Bender and Wagner (J. Colloid
      Interface Sci. 172, 171 (1995) who used an optical technique.

PMID- 9245313
TI  - Dynamic Film and Interfacial Tensions in Emulsion and Foam Systems
AB  - In concentrated fluid dispersions the liquid films are under dynamic conditions
      during film rupture or drainage. Aqueous foam films stabilized with sodium
      decylsulfonate and aqueous emulsion films stabilized with the nonionic Brij 58
      surfactant were formed at the tip of a capillary and the film tension was
      measured under static and dynamic conditions. In the stress relaxation
      experiments the response of the film tension to a sudden film area expansion was
      studied. These experiments also allowed the direct measurement of the Gibbs film
      elasticity. In the dynamic film tension experiments, the film area was
      continuously increased by a constant rate and the dynamic film tension was
      monitored. The measured film tensions were compared with the interfacial tensions
      of the respective single air/water and oil/water interfaces, which were measured
      using the same radius of curvature, relative expansion, and expansion rate as in
      the film studies. It was found that under dynamic conditions the film tension is
      higher than twice the single interfacial tension (IFT) and a mechanism was
      suggested to explain the difference. When the film, initially at equilibrium, is
      expanded and the interfacial area increases, a substantial surfactant depletion
      occurs inside the film. As a result, the surfactant can be supplied only from the
      adjoining meniscus (Plateau border) by surface diffusion, and the film tension is
      controlled by the diffusion and adsorption of surfactant in the meniscus. The
      results have important implications for the stability and rheology of foams and
      emulsions with high dispersed phase ratios (polyhedral structure).

PMID- 9245314
TI  - Effect of the Spreading Coefficient on Three-Phase Flow in Porous Media
AB  - A pore-level network model has been developed to study the effect of spreading
      coefficients on three-phase flow through porous media. This model combines the
      morphological description of the pore space with pore-level displacement physics
      to model capillarity-controlled, immiscible gas invasion of a porous medium
      initially saturated with water and oil. Three displacement events are involved
      during gas invasion, namely, direct water drainage, direct oil drainage, and
      double drainage. Direct oil drainage and double drainage involve oil mobilization
      and consequently lead to oil recovery. Direct water drainage event is preferred
      over double drainage if the spreading coefficient is highly negative. The
      residual oil saturation to gasflood starting after a waterflood is higher for
      nonspreading oils than for spreading oils. In spreading oils, it is not a
      function of the spreading coefficient. In nonspreading oils, the residual oil
      saturation increases with the magnitude of the spreading coefficient. The
      residual oil saturation to gasflood is also a function of the initial oil
      saturation; it increases as the initial oil saturation increases. The increase is
      higher for nonspreading oils. The gas-oil capillary pressure is not a function of
      the liquid saturation alone, as is commonly presumed. It is a function of the
      spreading coefficient and the initial oil saturation, as well.

PMID- 9245315
TI  - Frequency Behavior of the Electro-optical Effect from Colloid Particles in
      Polyelectrolyte Solutions with Counterion Mixtures
AB  - The electric light scattering method was used to investigate the frequency
      behavior of ferric oxide particles in carboxymethylcellulose solutions containing
      mono- and divalent counterion mixtures. The dispersion curves of suspensions,
      stabilized by polyelectrolyte adsorption, were analyzed in terms of three
      relaxations: rotational relaxation of the polymer-coated particles (at
      frequencies below 1 kHz), low-frequency relaxation of the bound counterions
      polarization (at frequencies from 1 kHz to 10 kHz) and high-frequency relaxation
      of the free counterions polarization (at frequencies above 60 kHz) along the
      particle axis. The frequency behavior of the electro-optical effect from
      suspensions containing polyelectrolyte with counterions mixtures was explained in
      accordance with the theory that the fraction of free (mono- and divalent)
      counterions increases with increasing the equivalent fraction of divalent ions in
      the mixture. Immobility of the strongly bound divalent counterions at low field
      strengths is supposed to reduce their contribution in the low-frequency effect in
      comparison to the effect from the less bound monovalent counterions.

PMID- 9245316
TI  - Surface Precipitation of Co(II)(aq) on Al2O3
AB  - Surface precipitation is an important process in many areas of science and
      technology, including modeling contaminant segregation from groundwater to solid
      phases and dispersion of active phases on catalyst supports. XAFS, TEM, and XPS
      measurements of Co(II) sorbed on Al2O3 demonstrate that surface precipitates have
      formed from solutions that are undersaturated with respect to any known bulk
      solid phase. The precipitates have a structure similar to that of Co(OH)2(s), but
      are disordered and have a high concentration of Co vacancies. The data plus
      thermodynamic reasoning have been used to analyze the plausibility of various
      models for surface precipitation and to show that for Co(II)/Al2O3 it occurs by
      forming a double-hydroxide phase containing substrate-derived Al(III) ions. This
      idea was corroborated by mixing aqueous solutions of Al(III) and Co(II) at the pH
      and concentration of the sorption samples, forming a stable colloidal precipitate
      that is less soluble than either Al(OH)3 or Co(OH)2. The Co XAFS of this material
      was similar to that of the sorption samples. Successful quantitative models of
      metal ion transport in groundwater need to include the possibility of forming
      ternary and higher order precipitates that include ions derived from sparingly
      soluble solids. For catalyst impregnation, surface coprecipitation can prevent
      production of a well-dispersed precursor material.

PMID- 9245317
TI  - Apolar, Polar, and Electrostatic Interactions of Spherical Particles in
      Cylindrical Pores
AB  - A new Surface Element Integration (SEI) technique is developed for determination
      of the interaction energy of a spherical particle in a cylindrical pore based on
      the knowledge of the corresponding interaction energy per unit area between plane
      parallel half spaces. Like the celebrated Deryaguin's approximation, the SEI can
      be used for any component of the interaction energy (e.g., apolar Lifshitz-van
      der Waals, electrostatic, polar) whenever interaction between corresponding half
      spaces is known theoretically or experimentally. Accuracy of the SEI is assessed
      based on its comparison with the exact results for the van der Waals interaction
      energy. Results of the SEI are also compared with the approximate series solution
      for the electrostatic interaction in the Debye-Huckel approximation. While
      Deryaguin's approximation fails for the particle-pore geometry for small pores
      (<10 nm), the SEI is accurate for all realistic combinations of particle and pore
      radii, radial position of the particle, and decay length of interactions. Based
      on the SEI, the role of polar repulsion (hydration pressure) on the partitioning
      behavior of macromolecules across small pores is also studied. The hydration
      force in aqueous hydrophilic systems can lead to a significant lowering of the
      distribution coefficient in small pores characteristic of ultrafiltration.

PMID- 9245318
TI  - Studies on the Adsorption of Sulfapyridine at the Solution-Alumina Interface
AB  - The adsorption of Sulfapyridine (SP) onto the alumina surface has been carried
      out at room temperature to study the adsorption behavior of SP and its mode of
      interaction with the surface of alumina particles. It is found that various
      factors such as concentration of SP solution, required time for adsorption
      equilibrium, pH of the adsorbate solution, temperature of adsorption medium,
      presence of ions like PO43-, SO42-, and Cl- affect quantitatively the adsorption
      of SP. Various adsorption and kinetic parameters such as the adsorption isotherm,
      adsorption coefficient, rate constants for adsorption and desorption and surface
      coverage have also been evaluated. The present study is significant because
      knowledge of the exact interaction between the SP molecules and the alumina
      surface and the proper choice of experimental condition would be helpful in
      carrying out an optimum separation of sulfa drug compounds chromatographically.

PMID- 9245319
TI  - Spectroscopy of Rhodamine 6G Adsorbed on Sepiolite Aqueous Suspensions
AB  - Electronic absorption and fluorescence spectroscopies are applied to study the
      adsorption of rhodamine 6G dye on sepiolite particles in aqueous suspensions. The
      adsorption of the dye on the clay is performed for several loadings and stirring
      times after samples preparation. The monomer of the dye is adsorbed on the
      external surface of the clay for low loadings and short stirring times. The
      flocculation of the samples is observed for high relative dye/clay concentration
      samples. For intermediate loadings, the ageing of the samples leads to the
      presence of dye molecules in the interspace of clay aggregates, which are
      identified with the preflocculation state of the samples.

PMID- 9245320
TI  - Prediction of Critical Micelle Concentration Using a Quantitative Structure
      Property Relationship Approach
AB  - Relationships between the molecular structure and the critical micelle
      concentration (cmc) of anionic surfactants were investigated using a quantitative
      structure-property relationship approach. Measured cmc values for 119 anionic
      structures, representing sodium alkyl sulfates and sodium sulfonates with a wide
      variety of hydrophobic and hydrophilic structures, were considered. The best
      multiple linear regression model involved three terms (descriptors) and had a
      correlation coefficient of R2 = 0.940. Very good correlations (R2 = 0.988) were
      obtained using three descriptors for a subset of 68 structures, with structural
      variation only in the hydrophobic domain. From the descriptors used in these
      regressions, one can conclude that the cmc is primarily dependent on the size
      (volume or surface area) of the hydrophobic domain and to a lesser extent on the
      structural complexity of the surfactant molecule.

PMID- 9245321
TI  - Imaging of the Early Events of Classical Complement Activation Using Antibodies
      and Atomic Force Microscopy
AB  - In the present report we use atomic force microscopy (AFM) combined with antibody
      techniques to study the lateral distribution of specific serum proteins adsorbed
      onto flat silicon surfaces precoated with immunoglobulin G (IgG). Null
      ellipsometry was used as a complimentary technique to quantify the adsorbed
      protein layers. After 15 s of incubation in human blood serum a partial monolayer
      of randomly distributed serum proteins was observed. The following exposure to
      antibodies to complement factor 1q (anti-C1q) resulted in a development of
      enlarged protein aggregates and a significant increase in adsorbed mass.
      Conversely, exposure to antibodies to complement factor 3c (anti-C3c) resulted in
      only a few randomly distributed protein aggregates and a much smaller increase in
      adsorbed mass. After 60 s of serum incubation the entire surface was covered with
      a proteinaceous film with irregular topography. This layer bound large amounts of
      anti-C3c but showed significantly smaller affinity for anti-C1q. Prolonging the
      serum incubation to 30 min resulted in an increased thickness and roughness of
      the protein layer and caused a massive deposition of anti-C3c but no anti-C1q.
      The results suggests that the transient affinity of anti-C1q, seen on various
      classically complement activating surfaces, is due to a shielding of the
      initially adsorbed proteins by subsequently deposited layers of C3. The results
      also show that qualitative information of the lateral organisation of specific
      proteins in a heterogeneous mixture can be assessed using AFM in combination with
      immunological techniques.

PMID- 9245322
TI  - Influence of Different Parameters on a Dual-Fractal Analysis for Antigen-Antibody
      Binding Kinetics for Biosensor Applications
AB  - The diffusion-limited binding kinetics of antigen (or antibody) in solution to
      antibody (or antigen) immobilized on a biosensor surface is analyzed within a
      fractal framework. The fit obtained by a dual-fractal analysis is compared with
      that obtained from a single-fractal analysis. In some cases, the dual-fractal
      analysis provides an improved fit when compared with a single-fractal analysis.
      This was indicated by the regression analysis provided by Sigmaplot (46). It is
      of interest to note that the state of disorder (or the fractal dimension) and the
      binding rate coefficient both increase as the reaction progresses on the
      biosensor surface. For example, for the binding of HIV-1 p24 in solution to
      monoclonal antibody (MAb) 18 covalently attached to a biosensor surface (49), an
      increase in the fractal dimension by 59% from a value of Df1 equal to 1.91 to Df2
      equal to 2.95 leads to an increase in the binding rate coefficient by a factor of
      15 from k1 equal to 21.1 to k2 equal to 339. Also, the binding of MAb 6301 and
      6303 in solution to insulin growth factor binding protein-1 (IGFBP-1) covalently
      attached to the sensor surface is adequately described by a single-fractal
      analysis (48). The binding of MAb 6302 to IGFBP-1, however, requires dual
      fractals. This indicates a difference in the binding mechanisms of these MAbs.
      The different examples analyzed and presented together provide a means by which
      the antigen-antibody reactions may be better controlled by noting the magnitude
      of the changes in the fractal dimension and in the binding rate coefficient as
      the reaction progresses on the biosensor surface. Also, the magnitude of the
      changes in the binding rate coefficients (k1 and k2) and in the fractal
      dimensions (Df1 and Df2) as different parameters are changed for the different
      biosensor applications are of particular value.

PMID- 9245323
TI  - A Comparative Study on the Adsorption of Triton X-100 and Tween 20 onto Latexes
      with Different Interfacial Properties
AB  - In this paper we have studied the adsorption of two nonionic surfactants, Triton
      X-100 and Tween 20 (polyoxyethylene (20) sorbitan monolaurate) onto latexes with
      different interfacial properties. Four different samples of polystyrene beads
      were used in this study. A hydrophobic sample was prepared by conventional
      emulsion polymerization of styrene. Hydrophilic polymer colloids were prepared by
      the emulsifier-free emulsion copolymerization of styrene and 2
      hydroxyethylmethacrylate in different proportions and acrylic acid. In all cases
      potassium persulfate was used as initiator. In order to consider the mechanism of
      the adsorption at the different liquid-solid interfaces, adsorption isotherms
      under different pH and ionic strength conditions were performed. Electrokinetic
      characterization and colloidal stability of bare hydrophobic and hydrophilic
      latexes and the surfactant-latex complexes were compared to understand the effect
      of the nonionic surfactant on the electric double layer structure. The results
      showed that Tween 20 and Triton X-100 are adsorbed in the same way on surfaces
      with different polarity but in different amounts. Hydrophobic interaction is the
      main driving force in the adsorption. The effect of the adsorption on the
      electrokinetic properties and stability of the latexes was found to be different
      for hydrophobic and hydrophilic latexes as a consequence of the dissimilar
      interfacial properties of these two latex samples.

PMID- 9245324
TI  - Constructing a Proton Titration Curve from Ion-Step Measurements, Applied to a
      Membrane with Adsorbed Protein
AB  - A new measuring method is described for obtaining a proton titration curve. The
      curve is obtained from a microporous composite membrane, consisting of
      polystyrene beads in an agarose matrix, with lysozyme molecules adsorbed to the
      bead surface. The membrane is incorporated into a sensor system by deposition on
      a silicon chip with a pH-sensitive ion-sensitive field effect transistor (ISFET)
      located in the middle of a Ag/AgCl electrode. The actual measurement is performed
      by creating a stepwise change in the salt concentration of the bathing
      electrolyte (the ion step) and measuring the ISFET potential versus the Ag/AgCl
      electrode. This potential shows a transient change in the ion step, which
      indicates a transient pH change in the membrane. This procedure is repeated at a
      series of pH values. Equations are presented to calculate the proton titration
      curve of the membrane from the amplitude and duration of the measured transients.
      Measurements show qualitative agreement between the curves obtained and
      equilibrium titration experiments on the same system.

PMID- 9245325
TI  - Marangoni-Stress-Driven "Solitonic" (Periodic) Wave Trains Rotating in an Annular
      Container during Heat Transfer
AB  - Periodic wave trains can be induced at the surface of liquid layers when the
      liquid is heated from above. These wave trains are an oscillatory regime of the
      Marangoni-instability. They are studied in a circular annular container, in which
      a wave synchronization is possible. Two counter-rotating (periodic) wave trains
      can be observed at a moderate level of supercritical Marangoni-number values.
      During the head-on collisions of the waves a negative phase shift occurs. This is
      evidence of the nonlinear interaction of the waves and their "solitonic"
      properties.

PMID- 9245326
TI  - Dynamic Surface Tension Effects in Impact of a Drop with a Solid Surface
AB  - Recent research on free surface flows in the presence of surface-active species
      in which a fluid interface undergoes very large deformations, e.g., as in the
      deformation and breakup of drops in extensional flows under conditions of Stokes
      flow (Stone, H. A., and Leal, L. G., J. Fluid Mech. 220, 161 (1990)) (19) and the
      formation of drops from capillaries (Zhang, X., and Basaran, O. A., Phys. Fluids
      7, 1184 (1995)) (20) has shown that dynamic surface tension (DST) effects can
      radically alter the dynamics compared to situations in which the fluid interface
      is clean. In this paper, we present results of an experimental study that
      examines the impact with a solid substrate of drops of Newtonian liquids
      containing two commonly used surfactants. In the experiments, an ultra high-speed
      video and associated image analysis system is used to monitor the dynamics of the
      impact process. On account of the extremely large deformations that a drop
      exhibits and the large-amplitude oscillations that it undergoes upon impacting
      and spreading on the substrate, DST plays a complex and dominant role in
      determining the dynamics and the asymptotic state that is approached at large
      times. A major consequence of the presence of surfactant is that on the one hand
      its accumulation on the fluid interface reduces the surface tension and thereby
      enhances the spreading of the drop across the substrate. On the other hand, the
      non-uniform distribution of surfactant along the fluid interface gives rise to
      Marangoni stresses that inhibit drop spreading. Given the fact that many liquids
      used in atomization coating applications ranging from the spraying of
      agricultural chemicals to painting of substrates contain surfactants and/or other
      surface-active species, the fundamental results to be reported in this paper have
      important practical ramifications.

PMID- 9245327
TI  - A Comparison of Water-Sodium Dodecyl Sulfate Phase Transfer Linear Solvation
      Energy Relationships and Databases
AB  - Four linear solvation energy relationship (LSER) studies of solute partitioning
      in aqueous sodium dodecyl sulfate micellar solutions are compared. Two of the
      LSERs are based on compilations of literature data obtained from a variety of
      measurement techniques and under differing experimental conditions. A third study
      used micellar electrokinetic capillary chromatography (MEKC) to obtain partition
      coefficients, whereas our approach is based solely on a head space gas
      chromatographic (HSGC) method. Despite significant differences in the sizes of
      the solute sets, the four LSERs yield essentially equivalent chemical conclusions
      regarding the fundamental interactions controlling the partition process. In
      comparison to MEKC, HSGC does not require the presence of salt or buffers,
      although it can be done with such additives, including cosurfactants.
      Additionally, the HSGC method, unlike the MLC method, does not involve
      assumptions concerning the behavior of any stationary phase. There are few
      restrictions on the HSGC method since one can use it to study species which are
      present in very low concentrations and which do not have chromophores. Finally,
      based on Kamlet's recommendation that three to four solutes are needed to
      properly define each LSER coefficient, we suggest a set of about 20 preferred
      solutes to use for future LSER studies of micellar systems.

PMID- 9245328
TI  - Stability of a Nanometric Zirconia Colloidal Dispersion under Compression: Effect
      of Surface Complexation by Acetylacetone
AB  - The stability of a colloidal dispersion of nanometric zirconia particles has been
      studied during a compression process. Using the osmotic stress method, cycles of
      compression and reswelling were applied to the dispersion to test the
      reversibility of the process. Original dispersions are stable in a very limited
      pH range (0.5-2). At pH 3, the bare particles aggregate irreversibly under
      compression as checked by osmotic pressure and light and X-ray scattering
      measurements. To improve the stability, small organic complexing molecules
      (acetylacetone) were added to the original dispersion. The adsorbed monolayer on
      the particle surfaces acts as a steric barrier and prevents the two colloids from
      contacting. As a consequence, the dispersion becomes more compressible and the
      compression cycle is totally reversible. The experimental data are quantitatively
      reproduced with a classical theory of statistical mechanics of liquids based on a
      DLVO-like colloid-colloid potential.

PMID- 9245329
TI  - Polarization-Induced Atomic Reconfigurations of Glycine on a Metal Surface
AB  - The atomic reconfigurations of the simplest amino acid, glycine, at a realistic
      metal surface including a step and real surface charge are calculated. A boundary
      element method for determining the polarization-induced binding of molecules to
      surfaces in the presence of a dielectric is coupled to quantum-chemical
      calculations of the gas-phase molecule. Enthalpies and potentially derived
      fractional charges are determined using 6-31G** basis functions and MP2 level of
      theory for 216 different configurations of glycine. A parameterized model
      captures the quantum results as a function of bond lengths, angles, and dihedrals
      (average deviation of <1 kcal/mol). The molecule interacts with a discretized
      substrate, a face-centered cubic metal slab. The slab is treated as an explicit
      region of lattice atoms which may include real charge, requiring the boundary
      conditions and hence the formalism of R. J. Zauhar and R. S. Morgan [J. Mol.
      Biol. 186, 815 (1985)] to be modified. The results indicate that anionic glycine
      is bound to a Cu <100> surface by approximately 1.6 eV in the presence of a step
      of atomic dimensions in a geometric configuration in agreement with the
      experiments of K. Uvdal, P. Bodo, A. Ihs, B. Liedberg, and W. R. Salaneck [J.
      Colloid Interface Sci. 140, 207 (1990)]. Neutral glycine and zwitterionic glycine
      are found to be oriented with their N ends toward a neutral surface in agreement
      with experiment. These molecules are furthermore found to undergo a critical
      phenomenon: Their molecular orientation "flips" by 180&deg; with the introduction
      of a small, critical magnitude of real surface charge.

PMID- 9245330
TI  - Particle Aggregation due to Combined Gravitational and Electrophoretic Motion
AB  - The stability and pairwise aggregation rates of small spherical particles in a
      heterogeneous suspension under the collective effects of gravitational motion and
      electrophoretic migration are analyzed. The particles are assumed to be non
      Brownian, with thin, unpolarized double layers and different zeta potentials. The
      gravity vector and the electric field are assumed to be oriented in either the
      same direction or opposite directions. The particle aggregation rates are always
      enhanced by the presence of an electric field for parallel alignment of the
      gravitational and electrophoretic velocities. For antiparallel alignment with the
      magnitude of the gravitational relative velocity exceeding the magnitude of the
      electrophoretic relative velocity between two widely separated particles, the
      particle aggregation rates are reduced by the presence of the electric field, and
      there is a "collision-forbidden" region in parameter space due to stronger
      hydrodynamic interactions of the particles for gravitational motion than for
      electrophoretic motion. For antiparallel alignment with the magnitude of the
      electrophoretic relative velocity exceeding the magnitude of the gravitational
      relative velocity between two widely separated particles, the particle
      aggregation rates are enhanced by the presence of the electric field.

PMID- 9245331
TI  - Acid-Base Properties of Aqueous Illite Surfaces
AB  - In this paper, the acid-base properties of illite/water suspensions are examined
      using the constant capacitance surface complexation model. On the basis of
      results of potentiometric titrations and solubility experiments, we conclude that
      the proton reactions in the supernatants of illite suspensions can be
      successfully represented by proton reactions of Al(H2O)63+ and Si(OH)4 in water
      solutions. For illustrating the acidic characteristics of aqueous illite
      surfaces, two surface protonation models are proposed: (1) one site-one pKa
      model, identical withSOH right arrow over left arrow identical withSO- + H+,
      pKaint = 4.12-4.23; (2) two sites-two pKas model, identical withSIOH right arrow
      over left arrow identical withSIO- + H+, pKintaI = 4.17-4.44, and identical
      withSIIOH right arrow over left arrow identical withSIIO- + H+, [dipKintaII =
      6.35-7.74. Evaluation of these two models indicates that both of them can give
      good descriptions of the experimental data of systems with different illite
      concentrations and ionic strengths and that the one site-one pKa model can be
      considered as a simplification of the two sites-two pKas model. Since both models
      assume only deprotonation reactions at the illite surfaces, they suggest that the
      surface behavior of the illite is similar to that of amorphous SiO2. Model
      assumptions, experimental procedures, and evaluative criteria are detailed in the
      paper.

PMID- 9245332
TI  - Adsorption of Copper at Aqueous Illite Surfaces
AB  - In this paper, we conducted potentiometric titrations, batch adsorption
      experiments and FT-IR analysis to study the uptake of copper in illite/water
      suspensions and then applied the constant capacitance surface complexation model
      to interpret the reaction mechanism at the aqueous illite surfaces. Our research
      shows that the copper adsorption at these surfaces is strongly dependent on pH
      and that the adsorption causes a deprotonation of surface groups. We propose that
      the uptake of copper in the carbonate-free illite suspensions can be explained by
      the formation of mononuclear surface complexes, identical withSOCu+ and identical
      withSOCuOH, and a multinuclear surface complex, identical withSOCu2(OH)2+,
      followed by the formation of a bulk precipitate, Cu(OH)2(s), or a surface
      precipitate, identical withSOCu2(OH)3(sp). For the illite suspensions containing
      carbonates, we propose that the copper-illite interaction can be depicted by the
      formation of mononuclear surface complexes, identical withSOCu+ and identical
      withSOCuOH, followed by the formation of a copper hydroxylcarbonate precipitate,
      Cu2(OH)2CO3(s), rather than a copper hydroxide precipitate. The existence of
      Cu2(OH)2CO3(s) in the carbonate-containing illite suspensions was identified by
      FT-IR analysis.

PMID- 9245333
TI  - Simulation of Coating Layer Evolution and Drop Formation on Horizontal Cylinders
AB  - The lubrication form of the equations governing the flow of a thin liquid film on
      a horizontal right circular cylinder is derived. The equations are discretized
      and solved numerically using an alternating-direction implicit algorithm.
      Simulations demonstrate that the transition from a uniform coating to a final
      configuration of distinct drops follows a similar evolution for a wide range of
      cylinder radii. Initially gravity-driven drainage from the top and sides of the
      cylinder dampens the formation of any axial disturbances; only when this drainage
      slows do longitudinal waves begin to develop along the bottom of the cylinder.
      These waves grow rapidly and a series of alternating primary and satellite drops
      form during the transition from a linear to a nonlinear wave growth regime. This
      is followed by a slow drainage between adjacent drops as the drop pattern
      approaches an equilibrium state where surface tension forces exactly balance
      gravitational forces in each discrete drop. For large cylinder radii, these drops
      are localized on the bottom of the cylinder, while, for sufficiently small
      cylinder radii, these drops may wrap around the entire circumference of the
      cylinder. Integral measures of the evolving coating profile, such as the total
      energy and viscous dissipation rate, clearly show these growth phases. The
      equilibrium shape of large-amplitude pendant drops and the maximum sustainable
      drop volume for various cylinders are also considered.

PMID- 9245334
TI  - Analysis of Complexation Equilibria of Polyacrylic Acid by a Donnan-Based Concept
AB  - Complexation equilibria of uni- and divalent metal ions (Ag+, Ca2+, Cu2+, and
      Pb2+) with polyacrylic acid (PAA) have been studied at various degrees of
      dissociation (alpha) of PAA under different sodium salt concentration levels at
      25&deg;C. Both pH and pM(MZ+ = Ag+, Ca2+, Cu2+, and Pb2+) of equilibrium mixture
      solutions of MZ+/PAA/Na+ (excess) have been determined concurrently by a
      potentiometric titration method. The electrostatic effect inherent in the polyion
      metal ion binding equilibria has been evaluated by a Donnan-based concept and is
      corrected for by the use of a nonideality term of acid dissociation equilibria of
      the polyacid as a probe. For Ag+-PAA and Ca2+-PAA bindings, only monodentate
      ligand complexes, (MA)(Z-1), have proven to be formed, whereas for Cu2+ and Pb2+
      ion bindings, formation of both monodentate and bidentate ligand complexes have
      been observed. For both Cu2+-PAA and Pb2+-PAA systems, bidentate carboxylate
      complex formation is predominant at alpha > ca. 0.3, whereas at alpha < ca. 0.3,
      formation of monodentate carboxylate complexes becomes appreciable as alpha
      decreases. Stability constants of these complexes together with the intra
      molecular complexation equilibrium constants expressed by the ratio of the
      concentrations of bidentate complexes to monodentate complexes have successfully
      been evaluated and are compared with each other in order to discuss the
      multidentate complexation properties of the polycarboxylic acid.

PMID- 9245336
TI  - Preparation and Properties of Microcell Hybrids

PMID- 9245335
TI  - Multinuclear Magnetic Resonance Studies on Aqueous Suspensions of Synthetic
      Saponites
AB  - The structure at the liquid/solid interface of synthetic saponites is monitored
      by NMR methods. These results are compared with data obtained with a natural
      saponite. The mean orientation of interfacial water molecules is different for
      synthetic and natural saponites. Interaction of water molecules or counterions
      with the solid surface depends on the charge layer of the synthetic clays.
      Water/acetonitrile and sodium/tetrapropylammonium cation competitions have been
      studied. Significant changes of the orientation of interfacial water molecules
      and removal of sodium counterions are observed only with the lowest charged
      saponite.

PMID- 9245337
TI  - Production of Microcell Hybrids
AB  - Microcell fusion is a technology that involves the transfer of single or small
      clusters of intact chromosomes from one cell to another. The transferred
      chromosome can be stably retained in the recipient cell background under dominant
      selective pressure. Hybrid clones generated by this method result in
      karyotypically simple and homogeneous populations that are excellent resources
      for physical mapping. This article will describe a general strategy for the
      efficient micronucleation of human and rodent cell populations and their use as
      donors for microcell fusion into recipient cell lines.

PMID- 9245338
TI  - Complementation Mapping in Microcell Hybrids: Localization of XRCC4 to 5q15-q21
AB  - Microcell-mediated chromosome transfer (MMCT) offers a unique method for
      introducing tagged individual human chromosomes from mouse/human monochromosomal
      hybrids into cell lines displaying recessive mutant phenotypes. Functional
      analysis of the resultant microcell hybrids bearing different tagged individual
      human chromosomes permits identification of the complementing chromosome. Using
      this approach, a number of human DNA repair genes that complement DNA repair
      defects in Xeroderma pigmentosum, Ataxia telangiectasia, Bloom's syndrome, and
      rodent mutant cells have been mapped to specific chromosomes. In this paper, we
      present experiments performed to map a DNA double-strand break (dsb) repair gene,
      XRCC4, to human chromosome 5q15-q21. The introduction of human chromosome 5 into
      Chinese hamster mutant XR-1 cells corrected their X-ray sensitivity and DNA dsb
      repair deficiency. Loss of chromosome 5 and concomitant reversion to the
      radiosensitive phenotype confirmed the presence of XRCC4 on this chromosome.
      Analysis of DNA markers in radiation-resistant and -sensitive clones bearing
      different segments of chromosome 5 placed this gene in the region 5q15-q21. These
      studies demonstrate the application of MMCT technology to the genetic analysis of
      mutations that escape other experimental approaches.

PMID- 9245339
TI  - Regional Mapping Strategies Utilizing Microcell Hybrids
AB  - Microcell hybrids are useful resources for the mapping of human chromosomes. The
      procedure of microcell-mediated chromosome transfer often causes fragmentation of
      the donor chromosome. These fragment-containing microcell hybrids frequently
      contain a limited region around the locus used in selecting for retention of the
      chromosome in the hybrids, as well as other fragments from the donor chromosome.
      Monochromosomal microcell hybrids are useful as the donor cell line for creation
      of radiation-reduced hybrids. In contrast to fragment-containing microcell
      hybrids, radiation-reduced hybrids can be used to construct maps of regions of
      chromosomes that lack selectable markers. For both fragment-containing hybrids
      and radiation-reduced hybrids, the presence or absence of chromosome-specific
      sequences can be determined and used to construct a linear map of the chromosome.
      A protocol and general overview outlining the key concepts in the construction
      and analysis of a radiation-reduced hybrid panel is presented.

PMID- 9245340
TI  - Regulation of Tissue-Specific Gene Expression in Microcell Hybrids
AB  - Microcell-mediated chromosome transfer has been used to study genetic loci that
      can either activate or repress tissue-specific gene expression. We have used
      microcell hybrids to study activation of the muscle phenotype, as well as to
      identify a genetic locus responsible for inhibiting expression of the myogenic
      determination gene MyoD in primary fibroblasts. We have shown that microcell
      transfer of human fibroblast chromosome 11, which contains the MyoD locus, into
      the embryonic fibroblast cell line 10T1/2 results in activation of human MyoD
      and, consequently, activation of the entire muscle program of differentiation. In
      addition, chromosome segregation analysis indicates that the continued presence
      of human chromosome 11 is not required for maintenance of the myogenic phenotype.
      In contrast, whole-cell hybrids between 10T1/2 cells and primary nonmuscle cells
      fail to activate the muscle phenotype, suggesting the presence of MyoD inhibitory
      loci. Microcell hybrids retaining human fibroblast chromosome 4 fail to activate
      MyoD expression. Analysis of chromosome fragment-containing hybrids localizes the
      repressing activity to a small region on 4p.

PMID- 9245341
TI  - Identification of Tumor Suppressor Genes by Microcell Hybridization
AB  - Somatic cell genetic studies gave the first proof that functional tumor
      suppressor genes exist in mammalian genomes. Initial studies showed that whole
      cell hybrids between tumorigenic mouse or human cell lines and their normal
      counterparts became nontumorigenic upon inoculation into animals. However,
      identification of the operative tumor suppressor gene proved difficult due to the
      presence of the entire chromosomal complement of the normal cell parent. The
      development of the technique of microcell hybridization has provided a powerful
      method for overcoming this obstacle. Suppression of transformed properties of a
      cancer cell line upon transfer of single human chromosomes from normal cells
      directly maps the location of tumor suppressor activity. One can then use
      positional cloning techniques or differential expression strategies to isolate
      the functional tumor suppressor gene. We present a general strategy for the
      mapping of tumor suppressor genes in mammalian cells. We also outline some of the
      important control experiments as well as pitfalls encountered in such studies.

PMID- 9245342
TI  - Cloning Expressed cDNAS from Defined Chromosomal Regions Using Interspecific
      Microcell Hybrids and Subtractive Hybridization
AB  - Genes expressed from a defined genomic interval can be cloned using interspecific
      microcell hybrids and subtractive hybridization. This approach involves
      identifying a pair of interspecific hybrids that contain nearly isogenic
      fragments of a relevant chromosome, except for a region of nonoverlap
      encompassing the locus of interest. Radiolabeled cDNAs are synthesized from the
      hybrid cell line that contains the region of interest and hybridized in solution
      with an excess of biotinylated mRNA from the microcell hybrid lacking the region
      of interest. Subtracted cDNA probes enriched for sequences expressed from the
      nonoverlap region are isolated by the addition of streptavidin followed by
      organic extraction. These subtracted cDNA probes are used to screen a cDNA
      library prepared from an appropriate tissue, and candidate cDNAs are mapped by
      Southern hybridization to determine whether they are encoded within the
      nonoverlap region. This technique is an attractive alternative to other methods
      for identifying genes in a genomic region because it does not require that the
      gene of interest be localized to a minimal genetic interval, and the genomic DNA
      encompassing the region need not be cloned. Additionally, the method detects only
      expressed genes, simplifying the search for candidate genes within a genomic
      region.

PMID- 9245343
TI  - Homologous Modification of Human Chromosomal Genes in Chicken B-Cell x Human
      Microcell Hybrids
AB  - Chicken cell lines derived from avian leukosis virus-induced B-cell tumors are
      highly recombination-proficient. In these cells, homologous recombination between
      transfected DNA sequences and the corresponding chromosomal alleles occurs at
      high frequency, and targeting efficiencies of 10-90% can be obtained. We
      previously described a chromosome shuttle approach in which these cells can be
      used to modify human chromosomal alleles at high efficiency. In this method,
      marked human chromosomes are transferred into the chicken B-cell line, DT40, by
      microcell fusion. Human loci on the introduced chromosome can be modified
      efficiently by homologous recombination in the DT40/human microcell hybrids. The
      modified human chromosomes can then be transferred back to mammalian recipient
      cells for functional tests. In this report, we describe procedures for performing
      interclass microcell transfers between mammalian donor cells and DT40 recipients.
      We also describe transfection procedures for DT40/human microcell hybrids, which
      allow the recovery of transfectant clones containing specific homologous
      modifications. Finally, methods for transferring the modified human chromosomes
      from DT40/human microcell hybrids back to mammalian recipients are discussed.

PMID- 9245344
TI  - Fiber FISH as a DNA Mapping Tool
AB  - Fluorescence in situ hybridization (FISH) applied to metaphase chromosomes
      provides a mapping resolution of 1 to 3 Mb. FISH applied to interphase nuclei has
      a resolution of 50 kb and ranges 1-2 Mb. This better resolution is attributed to
      the higher degree of chromatin decondensation. Here, we describe FISH applied to
      naked DNA fibers (fiber FISH) and show that with such fully decondensed chromatin
      a resolution range of at least 1-400 kb can be obtained. Furthermore, we show
      that DNA fiber FISH provides a mapping tool that is highly supplementary to
      restriction mapping, because it permits very accurate gap and overlap sizing.
      Also, DNA fiber FISH provides the means to generate "color bar codes" for disease
      regions, which can be used to inspect patient DNAs for suspected gene
      rearrangements.

PMID- 9245345
TI  - Chromosome Microdissection-Based Techniques for Genome Analysis
AB  - It is now possible to start at a cytogenetically defined position in any
      eucaryotic genome and proceed toward isolation and identification of candidate
      genes known to map to that position, taking advantage of the new PCR
      amplification technology to produce position-specific DNA. The starting material
      for this very useful exercise is DNA microdissected from standard cytogenetic
      preparations. Here we describe techniques for acquiring useful samples of such
      DNA and strategies for the use of chromosome region-specific DNA for gene
      discovery projects.

PMID- 9245346
TI  - Detecting Genes with Ligases
AB  - The combination of synthetic oligonucleotide probes and DNA ligases is central to
      several recently developed genetic assays. Among the advantages of ligase
      mediated gene detection is that ligation of probe pairs provides highly specific
      detection of unique DNA sequences in genomic samples. The technique also allows
      for convenient distinction between sequence variants, since mismatched bases at
      the junction of the probe pair prevent ligation. Moreover, the circumstance that
      two probes are joined into one molecule can be exploited for detection in several
      ways, for instance by observing the change in probe size upon ligation.
      Alternatively, a detectable function on one probe can be demonstrated to become
      linked to a retrievable function on another one through ligation. Ligation
      products can also be recruited as templates for subsequent ligation reactions in
      powerful amplification schemes. So-called padlock probes lock to their targets by
      encircling them, remaining in place even after denaturing washes. Here, we will
      describe two ligase-mediated assays: one that serves to monitor the presence of
      common sequence variants in amplified samples of genomic DNA and another that is
      suitable to detect localized gene sequences.

PMID- 9245347
TI  - Genotyping Procedures in Linkage Mapping
AB  - Genotyping methods based on nonradioactive detection of PCR products and suitable
      for large-scale mapping projects are described. Two alternative techniques are
      proposed for the genotyping of polymorphic short tandem repeats or microsatellite
      markers. The first is designed for investigators who do not have access to
      automatic sequencing machines. This technique uses multiplex analysis of PCR
      products that are separated on sequencing gels, transferred to nylon membranes,
      and detected by hybridization with nonradioactive probes. The second technique
      uses automatic sequencing machines for the detection of fluorescently labeled PCR
      products. Another method describes the analysis of nonpolymorphic markers in
      whole-genome radiation hybrids. This method uses separation and detection of PCR
      products on agarose gels.

PMID- 9245348
TI  - Strategies for the Identification of Intron-Exon Boundaries and Point Mutations:
      The Example of the RET Proto-Oncogene
AB  - For any given gene, the identification of exon boundaries and the corresponding
      flanking intron sequences is the essential prerequisite for asking interesting
      questions related to its structural organization, spanning from the study of its
      evolution to the molecular mechanisms underlying possible alternative splicing.
      In addition, this type of knowledge allows us to carry out mutation screenings
      for whole exons when the gene in question is known or suspected to be responsible
      for a human disease phenotype. Several different strategies already used to
      establish the genomic organization of genes are presented in detail, along with
      appropriate examples, and they are compared to each other with respect to their
      requirements, efficiency, and applicability. Particular emphasis is given to the
      detailed description of the strategy used to study the intron-exon junctions and
      to establish the intron flanking sequences of the RET proto-oncogene, whose
      mutations cause Hirschsprung disease (or congenital megacolon) as well as
      different types of thyroid cancer.

PMID- 9245349
TI  - IRS-Bubble PCR: An Effective Method for Representative Amplification of Human
      Genomic DNA Sequences from Complex Sources
AB  - A rate-limiting step in the analysis of large segments of genomic DNA is the
      generation of a set of representative short single-copy sequences that can be
      used for development of fine-structure maps. In direct response to this need, we
      have developed interspersed repetitive DNA sequence (IRS)-bubble PCR. IRS-bubble
      PCR was designed to amplify the human DNA content of somatic cell hybrids, yeast
      artificial chromosomes (YACs), BACs, PACs, cosmids, and lambda phage and to
      result in greater complexity and representation than standard inter-IRS PCR.
      Here, we describe the application of IRS-bubble PCR to the generation of complex
      clone libraries for targeted STS development and the construction of robust
      hybridization probes for FISH mapping, "chromosome painting," or the assembly of
      cosmid contigs representing the human DNA content of somatic cell hybrids or
      YACs.

PMID- 9245350
TI  - Gene Copy Number Analysis by Fluorescence in Situ Hybridization and Comparative
      Genomic Hybridization
AB  - Fluorescence in situ hybridization (FISH) with gene- and locus-specific probes
      provides a rapid means to assess copy numbers of specific sequences in individual
      interphase nuclei. Recent technical improvements have made FISH applicable to the
      analysis of both fresh and archival tissue specimens in research as well as in
      diagnostic laboratories. FISH is limited to analysis of one or a few loci at a
      time, making genome-wide surveys impractical. Comparative genomic hybridization
      (CGH) was developed as a means to screen entire genomes for DNA sequence copy
      number changes. CGH is based on the cohybridization of differentially labeled
      test and reference DNAs to normal metaphase chromosomes. Measurement of the test
      to reference fluorescence ratios along all chromosomes provides information on
      chromosomal regions that are over- or underrepresented in the test genome. The
      use of these two techniques will be illustrated in the analysis of genetic
      changes in solid tumors. The techniques are complementary to one another and have
      proven to be highly useful for identification of previously unknown genetic
      changes and genes that play an important role in tumor progression.

PMID- 9245351
TI  - Primed in Situ Labeling as a Fast and Sensitive Method for the Detection of
      Specific DNA Sequences in Chromosomes and Nuclei
AB  - Primed in situ labeling (PRINS) has become a routine technique for the
      microscopical staining of specific DNA sequences in cells and nuclei. For this
      purpose, the technique has the general advantage of being fast, simple, and
      sensitive. Furthermore, the reaction characteristics of the technique enable it
      to discriminate efficiently among closely related sequences-sometimes even when
      these differ by only one base. This high selectivity is obtained partly because
      the technique works optimally with oligonucleotide probes, which select more
      efficiently among closely related sequences than cloned probes do. This
      selectivity is further enhanced because no labeling occurs subsequent to probe
      binding unless the hybridized probe can function as primer for DNA synthesis, a
      process that is efficient only when the probe (primer) matches the target
      perfectly. Should this in itself provide insufficient selectivity, the involved
      chain elongation of the probe can be used in various ways to increase the
      selectivity of the staining further. These features of the technique have made it
      attractive for the detection of repeated DNA sequences, which now can be detected
      with a one-step procedure of a few minutes' duration, and make it a good
      candidate for the future detection of single-base variations in single-copy
      sequences in situ.

PMID- 9245352
TI  - Identification of Disease Genes in Genetic Isolates
AB  - Genetic isolates represent exceptional resources in the identification of disease
      loci. Not only have specific monogenic diseases become enriched and families
      frequent enough to be utilized in linkage analyses, but also the vast majority of
      patients carry the same mutation and share identical chromosomal haplotypes at
      significant distances. Additionally, regional isolates often reveal an increased
      prevalence of common polygenic diseases, and a hypothesis that selected
      predisposing genes can be efficiently identified due to a restricted number of
      ancestor mutations seems relevant. The current genome map with highly informative
      markers provides the basic tools for a genome-wide random search of disease loci.
      Special strategies including maximal utilization of linkage disequilibrium and
      scanning for shared chromosomal regions can be adapted in isolated populations,
      and this should greatly enhance the efficiency of locus identification even in
      complex human diseases.

PMID- 9245353
TI  - Parallel Processing in Genome Mapping and Sequencing
AB  - Conventional genome mapping and sequencing involves the analysis and processing
      of individual samples and pieces of experimental data. Although these methods
      work, it is quite clear that more efficient and less expensive methods are
      needed. Our top down physical mapping experiments have focused on the parallel
      processing of information from multiple samples at one time. This approach has
      aided the construction of genomic restriction maps and allowed us to assess the
      degree of large-scale conservation across wide regions of the human genome. The
      principles of parallel processing were applied in top down experiments that
      ordered an overlapping cosmid library from the 14-Mb Schizosaccharomyces pombe
      genome. This approach produced an eight-fold increase in efficiency in clone
      ordering over similar efforts. Recently, we have developed an enhanced sequencing
      by hybridization protocol that allows DNA sequence information to be collected on
      a large number of samples at once. Our current research focuses on applying
      parallel processing principles to make genome-wide comparisons between pairs of
      samples for analyzing disease states.

PMID- 9245354
TI  - 17O-decoupled proton MR spectroscopy and imaging in a tissue model.
AB  - 17O-decoupled proton MR spectroscopy and imaging were implemented at 2 T. Their
      sensitivity and accuracy in vitro were examined using semisolid tissue phantoms
      doped with H2(17)O. A double-tuned solenoidal coil was used to irradiate the same
      volume of 17O and 1H nuclei, as well as to facilitate direct calibration of the
      decoupling power. Decoupling efficiency was optimized as was 17O detection
      sensitivity. Decoupling was most efficient at RF amplitudes below 2.5 kHz
      (expressed as gamma [17O] x H1), which is within the limits of the acceptable
      specific absorption rate. Propagation of error analysis demonstrated that 17O
      detection sensitivity is optimal at a TE equal to the T2 of 17O-depleted water
      protons. Based on Meiboom's work, a simple theory was formulated for estimating
      the transverse relaxivity of H2(17)O and the proton signal enhancement produced
      by decoupling. There was excellent agreement between theory and experiment.
      Overall, 17O-decoupled spectroscopy and imaging were highly sensitive and
      accurate in quantifying H2(17)O in vitro.

PMID- 9245355
TI  - New Semi-empirical Approach for the Calculation of 13C Chemical-Shift Tensors
AB  - The semi-empirical bond polarization theory is applied to the calculation of 13C
      chemical-shift tensors. This method allows prediction of shift tensors with
      deviations from experiment comparable to the errors of the ab initio methods. In
      contrast to ab initio calculations, a set of empirical parameters is needed,
      which can be estimated from experimental chemical-shift tensors solving a set of
      linear equations. The coefficients of this overdetermined set of equations are
      bond polarization energies that must be calculated within the framework of this
      theory. The parameters for C-C, C-H, and C-O bonds of sp3 and sp2 hybridized
      carbons and C-N bonds of sp3 carbons were obtained from 606 equations formed from
      experimental data from 20 substances taken from the literature. The substances
      include sugars, aromatic compounds, amino acids, and organic acids. The mean
      deviation of calculated from experimental 13C chemical-shift tensor components is
      9 ppm.

PMID- 9245356
TI  - Accelerated Relaxation of Sensitive Nuclei for Enhancement of Signal-to-Noise
      with Time
AB  - A pulse sequence is proposed that accelerates the relaxation of sensitive nuclei
      through inverse polarization transfer from insensitive nuclei that have been
      subject to NOE during their detection: the sequence is designed to replace normal
      intersequence relaxation delays. Typically, for the observation of {1H}-13C, the
      13C relaxes during data acquisition and is enhanced by NOE from decoupled 1H's.
      After data acquisition the 13C polarization can be transferred to 1H in order to
      step-jump accelerate the relaxation of 1H and hence provide 1H polarization more
      rapidly for transfer to 13C during the next repetition of polarization-transfer
      sequences. It is suggested that the sequence (SNARE) can advantageously replace
      the relaxation delays in many common sequences. The benefits of so doing are
      illustrated using PENDANT and DEPT for 13C investigations. Conditions for the
      implementation of SNARE are proposed, and it is demonstrated that there is a
      range of spectral-acquisition parameters of practical interest for which the
      method can be beneficial. Experimental time savings in achieving a chosen S/N
      typically exceed 30%.

PMID- 9245357
TI  - A Double-Modulation ESR Study of Internal Dynamics in the Glassy Polymer Matrix
      Detected by a Nitroxide Spin Probe
AB  - The double-modulation ESR spin-probe technique was employed to study slow
      motional dynamics in amorphous polymer matrices of polybutadiene,
      polyisobutylene, poly(methyl methacrylate), and paraffin. It was shown that the
      low-lying excitation levels of the polymer matrix, found in the range from 77 to
      190 K below the internal spin-probe transition, affect the effective relaxation
      rate of a perdeuterated nitroxide probe. The interrelationship between the
      effective relaxation rates and the local molecular dynamics of side-chain groups
      attached to the polymer backbone was observed. Possible relaxation mechanisms are
      discussed within the electron-nuclear dipolar interaction.

PMID- 9245358
TI  - Protein heteronuclear NMR assignments using mean-field simulated annealing.
AB  - A computational method for the assignment of the NMR spectra of larger (21 kDa)
      proteins using a set of six of the most sensitive heteronuclear multidimensional
      nuclear magnetic resonance experiments is described. Connectivity data obtained
      from HNC alpha, HN(CO)C alpha, HN(C alpha)H alpha, and H alpha (C alpha CO)NH and
      spin-system identification data obtained from CP-(H)CCH-TOCSY and CP-(H)C(C alpha
      CO)NH-TOCSY were used to perform sequence-specific assignments using a mean-field
      formalism and simulated annealing. This mean-field method reports the resonance
      assignments in a probabilistic fashion, displaying the certainty of assignments
      in an unambiguous and quantitative manner. This technique was applied to the NMR
      data of the 172-residue peptide-binding domain of the E. coli heat-shock protein,
      DnaK. The method is demonstrated to be robust to significant amounts of missing,
      spurious, noisy, extraneous, and erroneous data.

PMID- 9245359
TI  - Strategies for Rapid NMR Rheometry by Magnetic Resonance Imaging Velocimetry
AB  - Strategies for NMR-based rheometry are discussed with particular attention given
      to ease of implementation, robustness, and measurement speed. The techniques are
      based on NMR velocimetry of Poiseuille flow, and together with measurements of
      the pressure drop, the velocimetric data may be processed to yield measures of
      the shear viscosity over the range of shear rates present in the Poiseuille flow
      field of the test fluid. Methods for NMR velocimetry are briefly reviewed, and
      three methods all based on the pulsed-field-gradient technique are compared
      experimentally; they involve (1) direct two-dimensional imaging of the tube cross
      section, (2) one-dimensional imaging of a Cartesian projection of the tube cross
      section followed by Abel inversion to obtain radial profiles, and (3) measurement
      of the bulk velocity spectrum of the tube cross section and conversion to the
      radial velocity profile. The second and third of these techniques allow the most
      rapid measurements (potentially less than one minute) and show promise for on
      line NMR rheometry.

PMID- 9245360
TI  - The Methyl-Rotor Electron-Spin Dynamics in the Smoluchowski Drift-Diffusional
      Framework
AB  - The EPR behavior of the internal motion of the methyl fragment in radicals is
      simulated using the Smoluchowski drift diffusion model. EPR stochastic Liouville
      lineshape calculations using this model are presented, allowing the exploration
      of the whole span of conditions between the discrete-site-exchange and the
      stepless-free-diffusion limits and offering a unification of these two
      approximate theories. An accurate value of the correlation time for the isotropic
      hyperfine interaction is calculated for the full ranges of the parameters
      describing the system and is compared to those given by the approximate models in
      the two limiting cases, allowing for a discussion of their quality. Long and
      short correlation time limit spectra are reported and interpreted using analytic
      models. For the isotropic hyperfine interaction studied here, no broadening
      effects are observed under Redfield (strong narrowing) conditions. This suggests
      absence of lifetime broadening effects in agreement with site-model results. The
      addition of a cos varphi term in the hyperfine interaction is essential for
      pyramidal radical centres, as is demonstrated by simulation of experimental
      reports in the literature.

PMID- 9245361
TI  - The intrinsic signal-to-noise ratio in human cardiac imaging at 1.5, 3, and 4 T.
AB  - Cardiac imaging is inherently demanding on the signal-to-noise performance of the
      MR scanner and may benefit from high field strengths. However, the complex
      behavior of the radiofrequency field in the human body at high frequencies makes
      model-based analyses difficult. This study aims to obtain reliable comparisons of
      the signal-to-noise profile in the human chest in vivo at 1.5, 3, and 4 T. By
      using an RF-field-mapping method, it is shown that the intrinsic signal-to-noise
      increases with the field strength up to 4 T with a less than linear relation. The
      RF field profile is markedly distorted at 4 T, and the onset of this distortion
      is dependent on the body size. The high power deposition and the consequences of
      the RF field distortion are discussed.

PMID- 9245362
TI  - Simulation of B1 field distribution and intrinsic signal-to-noise in cardiac MRI
      as a function of static magnetic field.
AB  - Two issues that pertain to the optimal static magnetic field for cardiac MRI were
      addressed: intrinsic signal-to-noise ratio (ISNR) and radiofrequency power
      deposition. From 1.5 to 9.5 T, proton Larmor frequencies of 63 to 400 MHz,
      numerical simulations were performed of the RF fields from a surface coil and a
      body coil loaded by a heterogeneous, three-dimensional, symmetric model of the
      human chest. The RF field distribution, the power required to produce the RF
      field, and the ISNR at the center of the heart were computed. The model was
      validated by comparison with experimental data up to 4 T. The RF field distortion
      was quantified and found to increase linearly up to 6 T due mostly to dielectric
      resonance modes. Body coil simulations beyond 6 T showed the onset of higher
      order modes at the center of the heart. A range of expected RF power requirements
      was constructed as a function of field up to 9.5 T for surface coils and up to
      6.8 T for body coils. Over this range of static field, ISNR for a constant coil
      geometry was bracketed by an upper limit that was slightly greater than linear
      with field and a lower limit that was slightly less than linear with field. The
      RF power and ISNR showed a strong dependence on chest thickness at 1.5 and 4.0 T.
      Additionally, independent of chest thickness, the model predicts a lower limit of
      a factor of 5 increase in RF power as the static field is increased from 1.5 to 4
      T. Implications for imaging with other nuclei are discussed. Methods for checking
      the self-consistency of electrodynamic simulations are presented.

PMID- 9245363
TI  - Planar quadrature coil design using shielded-loop resonators.
AB  - The shielded-loop resonator is known to have a low capacitive sample loss due to
      a perfect balancing. In this paper, it is demonstrated that shielded-loop
      technology also can be used to improve design of planar quadrature coils. Both a
      dual-loop circuit and especially a dual-mode circuit may benefit from use of
      shielded-loop resonators. Observations in measurements agree with theory for both
      a dual-loop coil and a dual-mode coil. The coils were designed for use as
      transmit/receive coil for 1H imaging and spectroscopy at 4.7 T in rat brain.

PMID- 9245364
TI  - A single-scan imaging technique for measurement of the relative concentrations of
      fat and water protons and their transverse relaxation times.
AB  - A two-component chemical-shift-imaging technique is described from which fat and
      water images can be obtained in a single scan and in the presence of an
      inhomogeneous field. In addition, the method provides transverse relaxation rates
      R2 and R2' separately for each of the spectral components. The method is a
      combination and extension of the GESFIDE [gradient echo sampling of FID and echo,
      J. Ma and F. W. Wehrli, J. Magn. Reson. B 111, 61 (1996)] and the multipoint
      Dixon techniques. It is based on sampling the descending and ascending portions
      of a Hahn spin echo with a train of gradient echoes which are spaced at one-half
      of the chemical-shift modulation period. Processing of the complex echo data,
      involving an automated phase unwrapping algorithm, affords relative amplitudes
      and transverse relaxation rates of the two spectral components. An additional
      benefit of the method is its superior signal-to-noise ratio resulting from echo
      summation. Applications targeted and illustrated involve MRI osteodensitometry of
      trabecular bone in the presence of varying fractions of hematopoietic and fatty
      bone marrow.

PMID- 9245365
TI  - Accurate Numerical Approximation to the Gauss-Lorentz Lineshape
AB  - The Gauss-Lorentz lineshape often observed in EPR or NMR is shown to be simply
      related to the complex error function. Using numerical algorithms developed for
      the evaluation of this function, experimental lineshapes can be accurately and
      rapidly simulated. Formulas are presented for the derivatives of the line profile
      with respect to the parameters and for the approximate computation of the overall
      linewidth. It is observed that accurate integrals require use of a wide
      integration interval.

PMID- 9245366
TI  - Spin Echoes after Arbitrary N Pulses
AB  - Based on the Bloch equations, the general response of a nuclear spin-&frac12;
      system to multiple RF pulses with arbitrary phases and flip angles is presented.
      The general solution is expressed in a form including the pathway vectors
      specifying the magnetization paths generated by a string of pulses. The pathway
      vectors are useful for predicting the exact positions, magnitudes, and number of
      echoes. Also, these vectors make it easy to trace the physical origin of an echo
      formation. It is shown that the maximum number of echoes after N pulses is (3N-1 
      1)/2 using this concept.

PMID- 9245368
TI  - REPULSION, A Novel Approach to Efficient Powder Averaging in Solid-State NMR
AB  - A novel approach to efficient powder averaging in magnetic resonance is
      presented. The method relies on a simple numerical procedure which based on a
      random set of crystallite orientations through simulation of fictive
      intercrystallite repulsive forces iteratively determines a set of orientations
      uniformly distributed over the unit sphere. The so-called REPULSION partition
      scheme is compared to earlier methods with respect to the distribution of
      crystallite orientations, solid angles, and powder averaging efficiency. It is
      demonstrated that powder averaging using REPULSION converges faster than previous
      methods with respect to the number of crystallite orientations involved in the
      averaging. This feature renders REPULSION particularly attractive for calculation
      of magic-angle-spinning solid-state NMR spectra using a minimum of crystallite
      orientations. For numerical simulation of powder spectra, the reduced number of
      required crystallite orientations translates into shorter computation times and
      simulations less prone to systematic errors induced by finite sets of
      nonuniformly distributed crystallite orientations.

PMID- 9245367
TI  - Measurement of the degree of coupled isotopic enrichment of different positions
      in an antibiotic peptide by NMR.
AB  - An experimental strategy for determining the extent to which multiply
      isotopically labeled fragments are incorporated intact into relatively
      complicated compounds of interest is presented. The NMR methods employed are
      based on isotope-filtered one-dimensional spectra and difference HSQC spectra
      incorporating a spin echo designed to report on the presence of a second NMR
      active isotope at a coupled site. They supplement existing methods for
      determining the extent of isotopic incorporation at individual sites to reveal
      whether two coupled labeled sites in a precursor are incorporated as an intact
      unit into products. The methods described also circumvent 1H signal overlap and
      distinguish between the effects of different nitrogens coupled to individual
      carbons. The somewhat complicated case of valclavam illustrates the method's
      utility in measuring the J coupling constants between 13C and nearby sites that
      are only fractionally labeled with 15N, and measuring the fraction of molecules
      in which 13C is coupled to 15N, at each of several sites. The 15N of [2-13C, 15N]
      labeled glycine is found to be incorporated into all three N positions of
      valclavam but most heavily into the N11 position. Specifically, 15N and 13C are
      incorporated into the N11 and C10 positions together as an 15N13C fragment
      approximately 8% of the time, whereas 15N is incorporated largely independently
      at the other positions.

PMID- 9245369
TI  - High-resolution spectra of liposomes using MAS NMR. The case of intermediate-size
      vesicles.

PMID- 9245370
TI  - Quick Recording of Pure Absorption 2D TOCSY, ROESY, and NOESY Spectra Using
      Pulsed Field Gradients

PMID- 9245371
TI  - Correlation of the 15N(i + 1), 13Calpha(i), and 1Halpha(i) Backbone Resonances in
      13C/15N-Labeled Proteins by the (CO)N(CO)CAH Experiment

PMID- 9245372
TI  - PGSE NMR Measurements of Convection in a Capillary

PMID- 9245373
TI  - Automated shimming for deuterated solvents using field profiling.

PMID- 9245374
TI  - A Graphical Approach to NMR Experimental-Parameter Selection

PMID- 9245375
TI  - Application of interlaced Fourier transform to echo-planar spectroscopic imaging.

PMID- 9245376
TI  - Improvements and extensions in the conformational database potential for the
      refinement of NMR and X-ray structures of proteins and nucleic acids.

PMID- 9245377
TI  - A half-volume coil for efficient proton decoupling in humans at 4 tesla.

PMID- 9245378
TI  - Two-dimensional NMR spectroscopy of peptides on beads.

PMID- 9245379
TI  - Pure-Phase Multidimensional NMR by Reference-Frequency Shift (RFS)

PMID- 9245380
TI  - Pure-Phase Homo- and Heteronuclear J Spectra with Tilted Cross Peaks for an
      Accurate Determination of Coupling Constants

PMID- 9245381
TI  - A Practical Method for Automated Shimming with Normal Spectrometer Hardware

PMID- 9245382
TI  - A Novel Pulse Sequence Element for Biselective and Independent Rotations with
      Arbitrary Flip Angles and Phases for I and I{S} Spin Systems

PMID- 9245383
TI  - DPPH as a Standard for High-Field EPR

PMID- 9245384
TI  - Field Stabilization and 2H NMR Spectroscopy in a 24.6 T Resistive Magnet

PMID- 9245385
TI  - Ultra-high-resolved HSQC spectra of multiple- 13C-labeled biofluids.

PMID- 9245387
TI  - Elucidation of Dipolar Coupling Networks under Magic-Angle Spinning

PMID- 9245386
TI  - Dipolar Oscillations in Cross-Polarized Peptide Samples in Oriented Lipid
      Bilayers

PMID- 9245388
TI  - Ipriflavone: Background

PMID- 9245397
TI  - A double mutation at the tip of the dimer interface loop of triosephosphate
      isomerase generates active monomers with reduced stability.
AB  - Triosephosphate isomerase (TIM) is a very stable dimer. In order to understand
      better the importance of dimerization for stability and catalytic activity, we
      have constructed a monomeric double-mutation variant. The dimer interface
      residues Thr75 and Gly76, which are at the tip of loop 3, have been substituted
      by an arginine and a glutamate, respectively. In wild type TIM, these two
      residues are at a distance of 27 A from the active site (as measured within the
      same subunit). This new variant, RE-TIM, was expressed in Escherichia coli,
      purified to homogeneity, and biochemically characterized. Sedimentation
      equilibrium ultracentrifugation runs showed that RE-TIM is a monomer in solution.
      Far-UV CD spectra indicate that this new variant is folded properly and that the
      secondary structure contents of RE-TIM are similar to those of wild type TIM. The
      monomeric RE-TIM has residual TIM activity. The thermal stability of RE-TIM is
      lower than that for wild type TIM. CD melting curves for RE-TIM and wild type TIM
      show Tm values of 52 and 57 degrees C, respectively, in the presence of the
      active site ligand 2-phosphoglycolate at 1 mM. Previously, we have characterized
      two other monomeric forms of TIM: monoTIM and H47N-TIM. The properties of RE-TIM,
      H47N-TIM, and monoTIM are compared, and it is argued that the properties of RE
      TIM will be very similar to those of wild type monomeric subunits. This implies
      that wild type monomeric subunits have some stability and are catalytically
      active. It is also inferred that these monomeric subunits have flexible loops
      which rigidify at the dimer interface on dimerization, causing a 1000-fold
      increase of kcat and a 10-fold decrease of Km.

PMID- 9245398
TI  - The entropic penalty of ordered water accounts for weaker binding of the
      antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and
      crystallographic study.
AB  - Novobiocin is an antibiotic which binds to a 24 kDa fragment from the B subunit
      of DNA gyrase. Naturally occurring resistance arises from mutation of Arg-136
      which hydrogen bonds to the coumarin ring of novobiocin. We have applied
      calorimetry to characterize the binding of novobiocin to wild-type and R136H
      mutant 24 kDa fragments. Upon mutation, the Kd increases from 32 to 1200 nM at
      300 K. The enthalpy of binding is more favorable for the mutant (DeltaH degrees
      shifts from -12.1 to -17.5 kcal/mol), and the entropy of binding is much less
      favorable (TDeltaS degrees changes from -1.8 to -9.4 kcal/mol). Both of these
      changes are in the direction opposite to that expected if the loss of the Arg
      residue reduces hydrogen bonding. The change in heat capacity at constant
      pressure upon binding (DeltaCp) shifts from -295 to -454 cal mol-1 K-1. We also
      report the crystal structure, at 2.3 A resolution, of a complex between the R136H
      24 kDa fragment and novobiocin. Although the change in DeltaCp often would be
      interpreted as reflecting increased burial of hydrophobic surface on binding,
      this structure reveals a small decrease. Furthermore, an ordered water molecule
      is sequestered into the volume vacated by removal of the guanidinium group. There
      are large discrepancies when the measured thermodynamic parameters are compared
      to those estimated from the structural data using empirical relationships. These
      differences seem to arise from the effects of sequestering ordered water
      molecules upon complexation. The water-mediated hydrogen bonds linking novobiocin
      to the mutant protein make a favorable enthalpic contribution, whereas the
      immobilization of the water leads to an entropic cost and a reduction in the heat
      capacity of the system. Such a negative contribution to DeltaCp, DeltaH degrees ,
      and TDeltaS degrees appears to be a general property of water molecules that are
      sequestered when ligands bind to proteins.

PMID- 9245399
TI  - Characterization of lanthanide ion binding to the EF-hand protein S100 beta by
      luminescence spectroscopy.
AB  - S100 beta is a member of a group of low-molecular weight acidic calcium binding
      proteins widely distributed in the vertebrate nervous system containing two helix
      loop-helix calcium binding motifs (sites I and II). In addition, S100 beta also
      has auxiliary Zn2+ binding sites that are distinct from the Ca2+ binding sites.
      Luminescence spectroscopy using Eu3+ and Tb3+ as spectroscopic probes for Ca2+ is
      used to characterize the Ca2+ binding sites of this protein. Eu3+-bound S100 beta
      shows two distinct Eu3+ binding environments from both the excitation spectrum
      and Eu3+ excited state lifetimes. Eu3+ bound to the classical EF hand site II has
      a Kd of 660 +/- 20 nM, whereas the dissociation constant for the pseudo-EF hand
      site I is significantly weaker. Lifetimes in H2O and D2O lead to the finding that
      there are four water molecules coordinated to the Eu3+ in the weakly binding site
      I and two water molecules to the tightly binding site II. Site II in S100 beta
      expectedly is very similar to high-affinity Ln3+ binding domains I and II in
      calmodulin. Eu3+ luminescence experiments with Zn2+-loaded S100 beta show that
      the lifetime for Eu3+ in site I in Zn2+-loaded S100 beta is significantly
      different than that in the absence of Zn2+. Tyrosine-17-sensitized Tb3+
      luminescence experiments indicate that the Tb3+ occupying the proximal weaker
      binding site I is sensitized, whereas Tb3+ in site II is not. The distance
      between sites I and II (15.0 +/- 0.4 A) in S100 beta was determined from Forster
      type energy transfer in D2O solutions containing bound Eu3+ donor and Nd3+
      acceptor ions. For Zn2+-S100 beta, the intersite distance is reduced to 13 +/-
      0.3 A. Location of histidine-15 close to pseudo-EF site I suggests that Zn2+
      binding likely changes the conformation of this site, causing a reduction of the
      intersite distance by approximately 2 A.

PMID- 9245400
TI  - Binding of ncd to microtubules induces a conformational change near the junction
      of the motor domain with the neck.
AB  - We have covalently attached an electron paramagnetic resonance (EPR) spin probe
      to Cys-670 of the motor domain of ncd (nonclaret disjunctional protein) in order
      to investigate conformational changes associated with the chemomechanical cycle.
      Spin-labeling is highly specific and does not affect ncd function as monitored by
      either the binding affinity to microtubules or the rate of ATP hydrolysis. The
      EPR spectra can be deconvoluted into two components, one that is highly mobile
      with respect to the protein and one that is strongly immobilized. In the absence
      of microtubules, the relative proportions of these two components varied with
      temperature, showing that the transition between them involves a large change in
      enthalpy (DeltaH degrees = -75 kJ/mol). This result implies that the two
      populations represent very different protein conformations. Binding to
      microtubules results in virtually all probes shifting into the immobilized
      component, independent of the nucleotide bound. Superposition of the structures
      of ncd and myosin subfragment 1 reveals that the labeled cysteine is very close
      to the region which is homologous to the helix containing the two reactive
      sulfhydryls in myosin and is approximately 10 A from the junction of the motor
      domain with the remainder of the molecule. We conclude that the binding of ncd to
      microtubules results in a conformational change in this region which may be
      involved in the working power stroke.

PMID- 9245401
TI  - Structure and function of the xenobiotic substrate-binding site and location of a
      potential non-substrate-binding site in a class pi glutathione S-transferase.
AB  - Complex structures of a naturally occurring variant of human class pi glutathione
      S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or (9R,10R)-9-(S
      glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene [(9R,10R)-GSPhen] have been
      determined at resolutions of 1.8 and 1.9 A, respectively. The crystal structures
      reveal that the xenobiotic substrate-binding site (H-site) is located at a
      position similar to that observed in class mu GST 1-1 from rat liver (rGSTM1-1).
      In rGSTM1-1, the H-site is a hydrophobic cavity defined by the side chains of Y6,
      W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately
      half hydrophobic and half hydrophilic and is defined by the side chains of Y7,
      F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A hydrogen
      bond network connects the five water molecules and the side chains of R13 and
      N204. V104 is positioned such that the introduction of a methyl group (the result
      of the V104I mutation) disturbs the H-site water structure and alters the
      substrate-binding properties of the isozyme. The hydroxyl group of Y7 forms a
      hydrogen bond (3.2 A) with the sulfur atom of the product. There is a short
      hydrogen bond (2.5 A) between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the
      hydroxyl group of Y108 as an electrophilic participant in the addition of
      glutathione to epoxides. An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid
      (HEPES) molecule is found in the cavity between beta2 and alphaI. The location
      and properties of this HEPES-binding site fit a possible non-substrate-binding
      site that is involved in noncompetitive inhibition of the enzyme.

PMID- 9245402
TI  - Probing the hydrophobic interactions in the skeletal actomyosin subfragment 1 and
      its nucleotide complexes by zero-length cross-linking with a nickel-peptide
      chelate.
AB  - The complex of Ni(II) and the tripeptide Gly-Gly-His catalyzes, in the presence
      of monoperoxyphthalic acid, a zero-length protein-protein cross-linking via an
      oxidative radical pathway involving mainly aromatic amino acids and not at all
      nucleophilic residues [Brown, K. C., Yang, S.-H., and Kodadek, T. (1995)
      Biochemistry 34, 4733-4739]. We have taken advantage of this unprecedented cross
      linking system to directly and selectively probe the solution structure and
      functioning of the hydrophobic interface between F-actin and skeletal myosin
      subfragment 1 (S-1) at the level of its aromatic components, in the absence and
      in the presence of nucleotides (ATP and ADP) or nucleotide analogs (AMPPNP, PPi,
      and ADP. AlF4). Following verification of the structure of the Ni(II)-peptide
      chelate and of its oxidized active form by electrospray mass spectrometry,
      complexes of F-actin and S-1 or proteolytic S-1 derivatives and complexes of S-1
      and proteolytic F-actin derivatives were readily cross-linked under various
      controlled conditions without apparent alteration of the acto-S-1 recognition.
      The covalent adducts were identified on electrophoretic gels using specific
      protein labeling with the oxidation-resistant fluorophor, monobromobimane,
      combined with immunochemical staining. Two types of actin-heavy chain conjugates
      were produced. One, with a mass of 180 kDa, was formed in the rigor state or with
      ADP bound; the other one, with a mass of 200 kDa, was generated from the ternary
      complexes comprising a gamma-P-containing ligand. They were accumulated with an
      efficiency of 8 and 6%, respectively. For each reversible complex, the 180
      kDa:200 kDa band ratio was essentially as predicted from the nucleotide-dependent
      A to R equilibrium mechanism of the acto-S-1 interaction in solution [Geeves, A.
      M., and Conibear, P. B. (1995) Biosphys. J. 68, 194s-201s]. Both covalent species
      resulted from the cross-linking of an actin monomer to the central 50 kDa
      segment, and their distinct mobilities reflect gamma-P-mediated structural
      changes at or near the actin-50 kDa fragment interface. Peptide mapping showed
      the cross-linking to take place between the 506-561 S-1 segment and the 48-113
      actin stretch. The localization of these regions in the atomic F-actin-S-1 model
      implies that nucleotide-modulated close contacts, involving aromatic residues,
      are operating between the C-terminal helix of the hydrophobic strong actin
      binding motif of S-1 bound to the primary actin monomer and the top portion of
      the adjacent lower actin subunit. The specificity of the nickel-peptide cross
      linking, as assessed with the acto-S-1 complex, makes it a candidate for
      potential general use in investigations of the hydrophobic interactions within
      other protein motor-based assemblies.

PMID- 9245403
TI  - Spectroscopic and thermodynamic studies of DNA duplexes containing alpha-anomeric
      C, A, and G nucleotides and polarity reversals: coexistence of localized parallel
      and antiparallel DNA.
AB  - We present a thermodynamic, enzymatic, and spectroscopic study of three self
      complementary DNA decamer duplexes, d[GCGAATT-3'-3'-(alphaC)-5'-5'-GC]2 (alphaC),
      d[GCG-3'-3'-(alphaA)-5'-5'-ATTCGC]2 (alphaA), and d[GC-3'-3'-(alphaG)-5'-5'
      AATTCGC]2 (alphaG), which are identical in sequence but contain one alpha
      anomeric nucleotide per strand in a parallel orientation via 3'-3' and 5'-5'
      phosphodiester bonds; the results are placed in the context of our recent studies
      on the other members of this series, namely alphaT, d[GCGAAT-3'-3'-(alphaT)-5'-5'
      CGC]2, and the unmodified control [Aramini, J. M., et al. (1996) Biochemistry 35,
      9355-9365]. On the basis of UV hyperchromicity and melting profiles as well as 1H
      and 31P nuclear magnetic resonance (NMR) spectroscopic data, we conclude that all
      five constructs form stable duplexes, with very comparable structural features
      that are consistent with an overall right-handed, antiparallel B-DNA motif and
      Watson-Crick base pairing throughout. However, each of the alpha-containing
      sequences exhibits unique thermodynamic and structural differences ascribed to
      the nature (and position) of the alpha-nucleotide. First, the thermostability of
      these duplexes decreases from the control to alphaC in the following series:
      control > alphaT approximately alphaA approximately alphaG > alphaC. Second, in
      each of the four alpha-duplexes, 1H and 31P chemical shift differences compared
      to those of the control duplex are largely confined to the region encompassing
      the alpha-nucleotide and unnatural phosphodiester linkages, as well as
      neighboring nucleotides. Surprisingly, for alphaC, these modifications result in
      a significant alteration to the backbone conformation at the phosphodiester group
      directly across from the 3'-3' linkage. Finally, spin-spin (J) coupling data,
      specifically Sigma1', indicate that the vast majority of the furanose rings in
      these duplexes display a high propensity for adopting the S pucker. However, in
      alphaC, alphaA, and alphaT (but not alphaG), the sugar ring conformation in the
      nucleotide immediately following the 5'-5' linkage is described by an
      approximately equal distribution between the N and S conformers.

PMID- 9245404
TI  - In vitro selection of dopamine RNA ligands.
AB  - RNA aptamers that specifically bind dopamine have been isolated by in vitro
      selection from a pool of 3.4 x 10(14) different RNA molecules. One aptamer
      (dopa2), which dominated the selected pool, has been characterized and binds to
      the dopamine affinity column with a dissociation constant of 2.8 microM. The
      specificity of binding has been determined by studying binding properties of a
      number of dopamine-related molecules, showing that the interaction with the RNA
      might be mediated by the hydroxyl group at position 3 and the proximal aliphatic
      chain in the dopamine molecule. The binding domain was initially localized by
      boundary experiments. Further definition of the dopamine binding site was
      obtained by secondary selection on a pool of sequences derived from a partial
      randomization of the dopa2 molecule. Sequence comparison of a large panel of
      selected variants revealed a structural consensus motif among the active
      aptamers. The dopamine binding pocket is built up by a tertiary interaction
      between two stem and loop motifs, creating a stable framework in which five
      invariant nucleotides are precisely arrayed. Minimal active sequence and key
      nucleotides have been confirmed by the design of small functional aptamers and
      mutational analysis. Enzymatic probing suggests that the RNA might undergo a
      conformational change upon ligand binding that stabilizes the proposed tertiary
      structure.

PMID- 9245405
TI  - The tetranuclear manganese cluster in photosystem II: location and magnetic
      properties of the S2 state as determined by saturation-recovery EPR spectroscopy.
AB  - The spin-lattice relaxation enhancement of the dark-stable tyrosine radical, YD.,
      by the S2 state of the O2-evolving complex (OEC) of photosystem II (PSII) has
      been measured by using saturation-recovery EPR spectroscopy. Two forms of the S2
      state have been compared: the multiline EPR signal species in untreated PSII and
      the altered multiline EPR signal species in NH3-treated PSII. Previous work has
      shown that the non-single-exponential spin-lattice relaxation kinetics of YD. in
      S2-state PSII result from a dipole-dipole interaction with the Mn4 cluster of the
      OEC. By taking into account the temperature variation of the effective magnetic
      moment of the S2-state multiline EPR signal form of the OEC, we provide a
      quantitative analysis of its temperature-dependent enhancement of the spin
      lattice relaxation of YD.. Different spin states of the Mn4 cluster in the S2
      state are responsible for the effect at different temperature regimes: for T </=
      10 K, it is the ground spin state (S = 1/2); for T >/= 30 K, it is the first
      excited spin state; and at intermediate temperatures, the contributions of the
      two spin states are comparable. The relaxation enhancement of YD. is equivalent
      for both forms of the S2-state multiline EPR signal examined, indicating that the
      magnetic properties of the Mn4 cluster are very similar in the S2 state for both
      untreated and NH3-treated PSII. EPR progressive microwave-power saturation has
      also been used to assess the spin-lattice relaxation properties of the Mn4
      cluster giving the altered S2-state multiline EPR signal in the NH3 derivative of
      PSII. The Orbach mechanism is shown to provide the dominant relaxation pathway;
      the energy difference between the ground and first excited spin states is
      estimated to be 30 +/- 2 cm-1, which is very similar to the value found for the
      S2-state multiline EPR signal species in untreated PSII. Below 4 K, the
      effectiveness of the S2-state multiline EPR signal species as a spin relaxation
      enhancer of YD. drops dramatically. This is interpreted to occur because of
      temperature-dependent 55Mn nuclear spin-lattice relaxation which causes averaging
      of the effective Larmor frequency of the S2-state multiline EPR signal species
      during the time scale for spin-lattice relaxation of YD.; because the line shape
      of the S2-state multiline EPR signal is dominated by isotropic 55Mn nuclear
      hyperfine splittings, such nuclear relaxation processes allow frequencies in near
      resonance with that of YD. to be accessed, thereby producing a greater relaxation
      enhancement. By using a dipolar model that includes the line shapes of both the
      YD. and S2-state multiline EPR signals, the spin-lattice relaxation enhancement
      of YD. is analyzed to obtain a lower limit of 22 A for the distance between YD.
      and the OEC. Together with recent studies showing a close proximity of the Mn4
      cluster to YZ., these results provide further support for an asymmetric location
      of the Mn4 cluster with respect to the two redox-active tyrosines in PSII.

PMID- 9245406
TI  - Peptide binding in OppA, the crystal structures of the periplasmic oligopeptide
      binding protein in the unliganded form and in complex with lysyllysine.
AB  - The periplasmic oligopeptide binding protein, OppA, acts as the initial receptor
      for the uptake of peptides by the oligopeptide permease (Opp) in Gram-negative
      bacteria. Opp will handle peptides between two and five amino acid residues
      regardless of their sequence. The crystal structures of a series of OppA-peptide
      complexes have revealed an enclosed but versatile peptide binding pocket and have
      illustrated how tri- and tetrapeptide ligands are accommodated. Here, the crystal
      structures of (i) OppA complexed with a dipeptide (lysyllysine) and (ii)
      unliganded OppA have been solved using X-ray data extending to 1.8 and 2.4 A
      spacing, respectively. In the dipeptide complex, the alpha-amino group of the
      ligand is anchored through an ion pair interaction with Asp419, as observed in
      complexes with longer peptides. However, its alpha-carboxylate group forms water
      mediated interactions with the guanidinium groups of Arg404 and Arg413 rather
      than the direct salt bridges to Arg413 and His371 observed in the tripeptide and
      tetrapeptide complexes, respectively. Isothermal titration calorimetric
      measurements of the binding of lysine-containing peptides of different lengths to
      OppA show that the dipeptide, KK, is bound with approximately 60-fold lower
      affinity than related tri- and tetrapeptides (KKK and KKKA, respectively). These
      data are discussed with reference to the calculated enthalpic and entropic
      contributions to ligand binding and the structures of the OppA peptide complexes.
      In the unliganded molecule, domain III has rotated as a rigid body through 26
      degrees away from domains I and II, exposing the ligand binding site. The water
      structure in the binding cleft shows similarities to that in the various OppA
      peptide complexes.

PMID- 9245407
TI  - Crystal structure and photodynamic behavior of the blue emission variant
      Y66H/Y145F of green fluorescent protein.
AB  - The crystal structure of a blue emission variant (Y66H/Y145F) of the Aequorea
      victoria green fluorescent protein has been determined by molecular replacement
      and the model refined. The crystallographic R-factor is 18.1% for all data from
      20 to 2.1 A, and the model geometry is excellent. The chromophore is non-native
      and is autocatalytically generated from the internal tripeptide Ser65-His66
      Gly67. The final electron density maps indicate that the formation of the
      chromophore is complete, including 1,2 dehydration of His66 as indicated by the
      planarity of the chromophore. The chromophore is in the cis conformation, with no
      evidence for any substantial fraction of the trans configuration or uncyclized
      apoprotein, and is well-shielded from bulk solvent by the folded protein. These
      characteristics indicate that the machinery for production of the chromophore
      from a buried tripeptide unit is not only intact but also highly efficient in
      spite of a major change in chromophore chemical structure. Nevertheless, there
      are significant rearrangements in the hydrogen bond configuration around the
      chromophore as compared to wild-type, indicating flexibility of the active site.
      pH titration of the intact protein and the chromopeptide (pKa1 = 4.9 +/- 0.1,
      pKa2 = 12.0 +/- 0.1) suggests that the predominant form of the chromophore in the
      intact protein is electrically neutral. In contrast to the wild-type protein
      [Chattoraj, M., King, B. A., Bublitz, G. U., & Boxer, S. G. (1996) Proc. Natl.
      Acad. Sci. U.S.A., 8362-8367], femtosecond fluorescence up-conversion
      spectroscopy of the intact protein and a partially deuterated form strongly
      suggests that excited-state proton transfer is not coupled to fluorescence
      emission.

PMID- 9245408
TI  - Mutagenesis of the Mn2+-binding site of manganese peroxidase affects oxidation of
      Mn2+ by both compound I and compound II.
AB  - The present study investigates whether compound I and compound II of manganese
      peroxidase from the white-rot fungus Phanerochaete chrysosporium utilize the same
      Mn-binding site for catalysis. Manganese peroxidase was expressed from its cDNA
      in Escherichia coli and refolded from inclusion bodies to yield fully active
      enzyme. Three mutants of the enzyme were generated by site-directed mutagenesis.
      Each of the three amino acid residues proposed to be involved in Mn2+ binding,
      E35, D179, and E39, was mutated. The acidic side chains of E35 and E39 were
      shortened by one carbon to the acidic group D, and the acidic side chain of D179
      was shortened by one carbon to the alkyl group A. These mutants, E35D, D179A, and
      E39D, were used to determine whether Mn2+ reacts at the same site with both
      compound I and compound II of manganese peroxidase and to determine whether
      phenolic substrates for the enzyme react at this site. Our results conclusively
      demonstrate that E35 and D179 residues are involved not only in Mn2+ binding but
      also in electron transfer from Mn2+ to the enzyme for both compound I and
      compound II. In contrast, E39 is not critically important to either process. None
      of the three residues is involved in reactions with phenolic substrates or with
      H2O2.

PMID- 9245409
TI  - Measurement of cofactor distances between P700.+ and A1.- in native and quinone
      substituted photosystem I using pulsed electron paramagnetic resonance
      spectroscopy.
AB  - The radical pair P700.+Q.- (P700 = primary electron donor, Q = quinone acceptor)
      in native photosystem I and in preparations in which the native acceptor (vitamin
      K1) is replaced by different quinones is investigated by pulsed EPR spectroscopy.
      In a two-pulse experiment, the light-induced radical pair causes an out-of-phase
      electron spin echo, showing an envelope modulation. From the modulation
      frequency, the dipolar coupling, and therefore the distance between the two
      cofactors, can be derived. The observation of nearly identical distances of about
      25.4 A between P700.+ and Q.- in all preparations investigated here leads to the
      conclusion that the reconstituted quinones are bound to the native A1 binding
      pocket. Since the orientation of the reconstituted naphthoquinone relative to the
      axis joining P700.+ and Q*- differs drastically from that of the native vitamin
      K1, it cannot be bonded to the protein in the same way as the native acceptor.
      This implies that the function of A1 as an electron acceptor does not depend on
      the orientation or hydrogen bonding of the quinone.

PMID- 9245410
TI  - Comparative EPR and redox studies of three prokaryotic enzymes of the xanthine
      oxidase family: quinoline 2-oxidoreductase, quinaldine 4-oxidase, and
      isoquinoline 1-oxidoreductase.
AB  - For three prokaryotic enzymes of the xanthine oxidase family, namely quinoline 2
      oxidoreductase, quinaldine 4-oxidase, and isoquinoline 1-oxidoreductase, the
      electron transfer centers were investigated by electron paramagnetic resonance.
      The enzymes are containing a molybdenum-molybdopterin cytosine dinucleotide
      cofactor, two distinct [2Fe-2S] clusters and, apart from isoquinoline 1
      oxidoreductase, a flavin adenine dinucleotide. The latter cofactor yields two
      different organic radical signals in quinoline 2-oxidoreductase and quinaldine 4
      oxidase, typical for the neutral and anionic form, respectively. A "rapid" Mo(V)
      species is present in all enzymes with small differences in magnetic parameters.
      From spectra simulation of 95Mo-substituted quinoline 2-oxidoreductase, a
      deviation of 25 degrees between the maximal g and 95Mo-hyperfine tensor component
      was derived. The very rapid Mo(V) species was detected in small amounts upon
      reduction with substrates in quinoline 2-oxidoreductase and quinaldine 4-oxidase,
      but showed a different kinetic behavior with considerable EPR intensities in
      isoquinoline 1-oxidoreductase. The FeSI and FeSII centers produced different
      signals in all three enzymes and, in case of isoquinoline 1-oxidoreductase,
      revealed a dipolar interaction, from which a maximum distance of 15 A between
      FeSI and FeSII was estimated. The midpoint potentials of the FeS centers were
      surprisingly different and determined for FeSI/FeSII with -155/-195 mV in
      quinoline 2-oxidoreductase, -250/-70 mV in quinaldine 4-oxidase, and +65/+10 mV
      in isoquinoline 1-oxidoreductase. The slopes of the fitting curves for the Nernst
      equation are indicative for nonideal behavior. Only in quinoline 2
      oxidoreductase, an averaged midpoint potential of the molybdenum redox pairs of
      about -390 mV could be determined. Both of the other enzymes did not produce
      Mo(V) signals in redox titration experiments, probably because of direct
      reduction of Mo(VI) to Mo(IV) in the presence of dithionite.

PMID- 9245411
TI  - Hydrogen bond network in the distal site of peroxidases: spectroscopic properties
      of Asn70 --> Asp horseradish peroxidase mutant.
AB  - The distal His in peroxidases forms a hydrogen bond with the adjacent Asn, which
      is highly conserved among many plant and fungal peroxidases. Our previous work
      [Nagano, S., Tanaka, M., Ishimori, K., Watanabe, Y., & Morishima, I. (1996)
      Biochemistry 35, 14251-14258] has revealed that the replacement of Asn70 in
      horseradish peroxidase C (HRP) by Val (N70V) and Asp (N70D) discourages the
      oxidation activity for guaiacol, and the elementary reaction rate constants for
      the mutants was decreased by 10-15-fold. In order to delineate the structure
      function relationship of the His-Asn couple in peroxidase activity, heme
      environmental structures of the HRP mutant, N70D, were investigated by CD, 1H
      NMR, and IR spectroscopies as well as Fe2+/Fe3+ redox potential measurements.
      While N70D mutant exhibited quite similar CD spectra and redox potential to those
      of native enzyme, the paramagnetic NMR spectrum clearly showed that the hydrogen
      bond between the distal His and Asp70 is not formed in the mutant. The
      disappearance of the splitting in the 1H NMR signal of heme peripheral 8-methyl
      group observed in 50% H2O/50% D2O solution of N70D-CN suggests that the hydrogen
      bond between the distal His and heme-bound cyanide is also disrupted by the
      mutation, which was supported by the low C-N vibration frequency and large
      dissociation constant of the heme-bound cyanide in the mutant. Together with the
      results from various spectroscopies and redox potentials, we can conclude that
      the improper positioning of the distal His induced the cleavages of the hydrogen
      bonds around the distal His, resulting in the substantial decrease of the
      catalytic activity without large structural alterations of the enzyme. The His
      Asn hydrogen bond in the distal site of peroxidases, therefore, is essential for
      the catalytic activity by controlling the precise location of the distal His.

PMID- 9245412
TI  - Membrane permeabilization mechanisms of a cyclic antimicrobial peptide,
      tachyplesin I, and its linear analog.
AB  - Tachyplesin I (T-SS), an antimicrobial peptide from Tachypleus tridentatus, has a
      cyclic antiparallel beta-sheet structure maintained by two disulfide bridges. The
      peptide effectively permeabilizes both bacterial and artificial lipid membranes.
      T-Acm, a linear analog peptide with the four SH groups protected by
      acetamidomethyl groups, exhibits a much weaker membrane-permeabilizing activity
      in spite of a greater disruption of the lipid organization [Matsuzaki, K.,
      Nakayama, M., Fukui, M., Otaka, A., Funakoshi, S., Fujii, N., Bessho, K., &
      Miyajima, K. (1993) Biochemistry 32, 11704-11710]. To clarify the efficient
      permeabilization mechanism of T-SS, we studied the interactions of both peptides
      with liposomes and planar lipid bilayers. The cyclic peptide capable of spanning
      the bilayer (ca. 3 nm length) was found to form an anion-selective pore and
      translocate across the bilayer coupled with the pore formation. A cis-negative
      transmembrane potential facilitated the pore formation compared with the cis
      positive potential. In contrast, the linear peptide failed to translocate.
      Instead, it impaired the membrane barrier by disrupting the lipid organization
      with morphological changes in the vesicles.

PMID- 9245413
TI  - Interaction of P-glycoprotein with defined phospholipid bilayers: a differential
      scanning calorimetric study.
AB  - One of the major causes of multidrug resistance in human cancers is expression of
      the P-glycoprotein multidrug transporter, which acts as a drug efflux pump. P
      Glycoprotein is a member of the ABC superfamily of membrane proteins, and is
      composed of 12 hydrophobic membrane-spanning segments and 2 cytoplasmic
      nucleotide binding domains. Membrane lipids are known to play an important role
      in the function of P-glycoprotein. In the present study, purified P-glycoprotein
      of high specific ATPase activity was reconstituted into defined bilayers of
      dimyristoylphosphatidylcholine (DMPC), and its effects on lipid thermodynamic
      properties were then investigated using differential scanning calorimetry. P
      Glycoprotein had a large perturbing effect on DMPC bilayers, even at relatively
      high lipid:protein ratios. The gel to liquid-crystalline phase transition
      temperature, Tm, was lowered on inclusion of P-glycoprotein in the bilayer, and
      the cooperativity of the transition was markedly reduced. The phase transition
      enthalpy, DeltaH, declined in a linear fashion with increasing P-glycoprotein
      content for lipid:protein ratios between 63:1 and 16:1 (w/w). Evaluation of these
      data using two different analytical methods indicated that P-glycoprotein
      perturbed either 375 or 485 phospholipids, withdrawing them from the phase
      transition. The DeltaH value for those lipids undergoing melting was similar to
      that of pure DMPC, which implies that their thermodynamic properties are
      essentially unchanged in the presence of P-glycoprotein. At lipid:protein ratios
      below 16:1 (w/w), transition enthalpy increased with higher P-glycoprotein
      content, until the DeltaH value reached that of pure DMPC. However, the lipid
      remained highly perturbed, as indicated by a very broad phase transition peak.
      This behavior may arise from either aggregation/oligomerization of P-glycoprotein
      within the bilayer or changes in the interaction of the transporter with the
      membrane at high density.

PMID- 9245414
TI  - Inhibitory effects of HepG2 cell-derived apolipoprotein A-I-containing
      lipoproteins on cholesteryl ester accumulation in macrophages.
AB  - We investigated the mechanisms of inhibitory effects on foam cell formation of
      apolipoprotein A-I-containing lipoproteins secreted by HepG2 cells (HepG2-HDL)
      using mouse peritoneal macrophages. When macrophages were incubated with
      acetylated low-density lipoprotein (acetyl-LDL) in the presence of HepG2-HDL,
      cholesterol ester (CE) accumulation in cells was reduced by 63%. This inhibitory
      capacity was almost similar to that of plasma high-density lipoprotein (HDL).
      When macrophages were converted to foam cells with acetyl-LDL and then reacted
      with HepG2-HDL or plasma HDL, the HDL-induced CE reduction was 2.2-fold greater
      than HepG2-HDL. Similar results were obtained using apo E-free HepG2-HDL. Since
      the inhibitory effect of HDL on acetyl-LDL-induced CE accumulation in macrophages
      is due largely to its cholesterol efflux capacity, these results suggest the
      presence of an additional mechanism for the inhibition of CE accumulation by
      HepG2-HDL. To investigate the mechanism, acetyl-LDL was reisolated from HepG2-HDL
      by Sephacryl S-300 gel filtration after incubation in a cell-free system.
      Reisolated acetyl-LDL showed a significant reduction in electrophoretic mobility.
      The extent of CE accumulation by reisolated acetyl-LDL was reduced by 20%
      compared with control acetyl-LDL. Moreover, its endocytic degradation by
      macrophages was reduced by 28%. HepG2-HDL also inhibited macrophage degradation
      of acetyl-LDL as well as oxidized LDL, a likely atherogenic lipoprotein. This
      inhibitory effect was ascribed to the HepG2-HDL subfraction containing pre-beta
      HDL. Our results indicated that apo A-I-containing lipoproteins as a
      physiological model of nascent HDL may inhibit foam cell formation by reducing
      ligand activity of atherogenic lipoproteins. These data possibly suggest
      inhibitory function of nascent HDL for the formation of foam cells in vivo.

PMID- 9245415
TI  - Action of Taiwan cobra cardiotoxin on membranes: binding modes of a beta-sheet
      polypeptide with phosphatidylcholine bilayers.
AB  - The interaction of Taiwan cobra cardiotoxin (CTX A3), a basic polypeptide
      consisting of three-fingered loops and five-strand beta-sheet structure, with
      zwitterionic dipalmitoylphosphatidylcholine (DPPC) has been studied by 31P and 2H
      NMR to understand the binding modes of CTX in membrane bilayers. The results, in
      conjunction with DPH fluorescence anisotropy and differential scanning
      calorimetry studies, show that CTX may penetrate and lyse the bilayers into small
      aggregates at a lipid/protein molar ratio of about 20 in the ripple Pbeta' phase.
      Elevating the temperature to that of the liquid crystalline Lalpha phase leads to
      the fusion of the small aggregates into larger ones as evidenced by the change of
      the isotropic signal into a magnetically aligned 31P signal with a marked
      reduction in the chemical shift anisotropy. 2H NMR study on deuterium-labeled
      DPPC in the head group and fatty acyl region as a function of temperature and CTX
      concentration reveals a molecular model that CTX undergoes a redistribution
      between penetrating and peripheral binding states depending on the temperature
      studied. In addition, both the conformational and dynamic states of the
      phosphocholine head group of DPPC bilayers are significantly perturbed in the
      presence of CTX. Structural consideration of the CTX molecule indicates that the
      penetration binding mode of CTX with the DPPC bilayer may involve a novel
      membrane-binding motif identified recently in the three-fingered loops of P-type
      CTX. CTX can only bind to DPPC membrane peripherally in the Lalpha phase due to
      the mismatch of their hydrophobic lengths.

PMID- 9245416
TI  - Spectroscopically distinct cobalt(II) sites in heterodimetallic forms of the
      aminopeptidase from Aeromonas proteolytica: characterization of substrate
      binding.
AB  - The Co(II)Zn(II)- and Zn(II)Co(II)-substituted derivatives of the aminopeptidase
      from Aeromonas proteolytica (AAP) were probed by EPR spectroscopy. EPR spectra of
      the high-spin S = 3/2 Co(II) ions in [CoZn(AAP)] and [ZnCo(AAP)] indicated that
      each metal binding site provides a spectroscopically distinct signature. For
      [CoZn(AAP)], subtraction of EPR spectra recorded at pH 7.5 and 10 revealed that
      two species were present and that the relative contributions to each of the
      experimental spectra were pH-dependent. The first EPR species, predominant at
      lower pH values, was simulated as a relatively featureless axial signal with geff
      values of 2.20, 3.92, and 5.23 which correspond to an Ms = |+/-1/2> ground state
      transition with a greal of 2.29 and an E/D of 0.1. The second species,
      predominant at high pH, was simulated with geff values of 1.80, 2.75, and 6.88
      and exhibited a characteristic eight-line 59Co hyperfine pattern with an Az(59Co)
      of 7.0 mT. These parameters correspond to an Ms = |+/-1/2> ground state
      transition with a greal of 2.54; however, the signal exhibited marked rhombicity
      (E/D = 0.32) indicative of an asymmetric tetrahedral or five-coordinate Co(II)
      ion. Summation of these two species provided an excellent simulation of the
      observed [CoZn(AAP)] EPR spectrum. The EPR spectrum of [ZnCo(AAP)] also contained
      two species, at least one of which also exhibited 59Co hyperfine features.
      However, this signal exhibited little pH dependence, and individual species could
      not be isolated. The addition of the competitive inhibitor 1-butaneboronic acid
      (BuBA) to [CoZn(AAP)] resulted in a distinct change in the EPR spectrum; however,
      addition of BuBA to [ZnCo(AAP)] left the EPR spectrum completely unperturbed.
      These data indicate that BuBA binds only to the first metal binding site in AAP
      and does not interact with the second site. On the basis of the X-ray
      crystallographic data for the transition state analog-inhibited complexes of AAP
      and the aminopeptidase from bovine lens, BuBA was reclassified as a substrate
      analog inhibitor rather than a transition state analog inhibitor as previously
      suggested [Baker, J. O., & Prescott, J. M. (1983) Biochemistry 22, 5322-5331].
      From difference spectroscopy and from the simulation of the [CoZn(AAP)] EPR
      spectrum, a third signal appearing upon BuBA binding was isolated. This signal
      was simulated with geff values of 2.08, 3. 15, and 6.15 which correspond to an Ms
      = |+/-1/2> ground state transition with a greal of 2.41 and an E/D of 0.22. This
      simulation also invoked an eight-line unresolved 59Co hyperfine pattern with an
      Az(59Co) value of 4.0 mT. Summation of the these three species provided an
      excellent simulation of the observed [CoZn(AAP)] + BuBA EPR spectrum at both pH
      values. This work establishes that substrate binds only to the first metal
      binding site in AAP and thus substantiates the first step in catalysis in the
      recently proposed mechanism of action for AAP [Bennett, B., & Holz, R. C. (1997)
      J. Am. Chem. Soc. 119, 1923-1933; Chen, G., et al. (1997) Biochemistry 36, 4278
      4286].

PMID- 9245417
TI  - EXAFS comparison of the dimanganese core structures of manganese catalase,
      arginase, and manganese-substituted ribonucleotide reductase and hemerythrin.
AB  - The solution structures of the binuclear Mn centers in arginase, Mn catalase, and
      the Mn-substituted forms of the Fe enzymes ribonucleotide reductase and
      hemerythrin have been determined using X-ray absorption spectroscopy (XAS). X-ray
      absorption near edge structure (XANES) spectra for these proteins were compared
      to those obtained for Mn(II) models. The Mn model spectra show an inverse
      correlation between the XANES peak maximum and the root-mean-square (RMS)
      deviation in metal-ligand bond lengths. For these complexes, the XANES maxima
      appear to be more effective than the 1s --> 3d areas as an indicator of metal
      site symmetry. Arginase and Mn-substituted ribonucleotide reductase have
      symmetric nearest neighbor environments with low RMS deviation in bond length,
      while Mn catalase and Mn-substituted hemerythrin appear to have a larger RMS bond
      length deviation. The 1s --> 3d areas for arginase and Mn-substituted
      ribonucleotide reductase are consistent with six coordinate Mn, while the 1s -->
      3d areas for Mn catalase and Mn-substituted hemerythrin are larger, suggesting
      that one or both of the Mn ions are five-coordinate in these proteins. Extended x
      ray absorption fine structure (EXAFS) spectra were used to determine the Mn2 core
      structure for the four proteins. In order to quantitate the number of histidine
      residues bound to the Mn2 centers, EXAFS data for the crystallographically
      characterized model hexakis-imidazole Mn(II) dichloride tetrahydrate were used to
      calibrate the Mn-imidazole multiple scattering interactions. These calibrated
      parameters allowed the outer shell EXAFS to be fit to give a lower limit on the
      number of bound histidine residues. The EXAFS spectra for Mn-substituted
      ribonucleotide reductase and arginase are nearly identical, with symmetric Mn
      nearest neighbor environments and outer shell scattering consistent with a lower
      limit of one histidine per Mn2 core. In contrast, the EXAFS data for Mn catalase
      and Mn-substituted hemerythrin show two distinct Mn-nearest neighbor shells,
      modeled as Mn-O at ca. 2.1 A and Mn-N at ca. 2.3 A, and outer shell carbon
      scattering consistent with a lower limit of ca. 2-3 His residues per Mn2 core.
      Only Mn catalase shows clear evidence for Mn...Mn scattering. The observed
      Mn...Mn distance is 3.53 A, which is significantly longer than the approximately
      3.3 A distances that are typically observed for Mn(II)2 cores with two single
      atom bridges, but which is typical of the distances seen in Mn(II)2 cores having
      one single atom bridge (e.g., aqua or hydroxo) together with one or two
      carboxylate bridges. The absence of EXAFS-detectable Mn...Mn interactions for the
      other three proteins suggests either that there are no single atom bridges in
      these cases or that the Mn...Mn interactions are more disordered.

PMID- 9245418
TI  - Structure and dynamics of pentaglycyl bridges in the cell walls of Staphylococcus
      aureus by 13C-15N REDOR NMR.
AB  - Whole cells and cell-wall fractions of Staphylococcusaureus have been labeled by
      various combinations of [1-13C]glycine, [15N]glycine, L--6-13C-lysine, L--6-15N
      lysine, D--1-13C-alanine, and D--15N-alanine. The resulting materials have been
      examined using 13C and 15N solid-state, magic-angle spinning NMR techniques
      including cross-polarization, double cross-polarization, and rotational-echo
      double resonance. The results of these measurements indicate that the
      peptidoglycan glycyl bridges are complete (five units long) and form cross-links
      between three-quarters of all peptide stems. The pentaglycyl bridges are
      immobilized in lyophilized cell-wall fractions in a compact conformation with
      inter-residue spacings comparable to those of an alpha helix. The bridges have a
      similar compact conformation in intact whole cells, regardless of whether the
      cells have been lyophilized or were hydrated and frozen at -10 degrees C. The
      bridges are also in a time-averaged compact conformation in whole cells at 0
      degrees C but with sizable structural fluctuations associated with local
      mobility. A small fraction of bridges are in extended-chain conformations.

PMID- 9245419
TI  - Solution structure of oxidized horse heart cytochrome c.
AB  - The solution structure of oxidized horse heart cytochrome c was obtained at pH
      7.0 in 100 mM phosphate buffer from 2278 NOEs and 241 pseudocontact shift
      constraints. The final structure was refined through restrained energy
      minimization. A 35-member family, with RMSD values with respect to the average
      structure of 0.70 +/- 0.11 A and 1.21 +/- 0.14 A for the backbone and all heavy
      atoms, respectively, and with an average penalty function of 130 +/- 4.0 kJ/mol
      and 84 +/- 3.7 kJ/mol for NOE and pseudocontact shift constraints, respectively
      (corresponding to a target function of 0.9 A2 and 0.2 A2), was obtained. The
      solution structure is somewhat different from that recently reported (Qi et al.,
      1996) and appears to be similar to the X-ray structure of the same oxidation
      state (Bushnell et al., 1990). A noticeable difference is a rotation of 17 +/- 8
      degrees of the imidazole plane between solid and solution structure. Detailed and
      accurate structural determinations are important within the frame of the current
      debate of the structural rearrangements occurring upon oxidation or reduction.
      From the obtained magnetic susceptibility tensor a separation of the hyperfine
      shifts into their contact and pseudocontact contributions is derived and compared
      to that of the analogous isoenzyme from S. cerevisiae and to previous results.

PMID- 9245421
TI  - Catalytic activities and structural properties of horseradish peroxidase distal
      His42 --> Glu or Gln mutant.
AB  - The distal histidine (His) is highly conserved in peroxidases and has been
      considered to play a major role as a general acid-base catalyst for peroxidase
      reaction cycle. Recently, however, the X-ray structure of chloroperoxidase from
      the marine fungus Caldariomyces fumago has revealed that a glutamic acid is
      located at the position where most of the peroxidase has a histidine residue,
      suggesting that the carboxyl group in the glutamic acid (Glu) can also assist
      cleavage of an O-O bond in peroxides [Sundaramoorthy, M., Terner, J., & Poulos,
      T. L. (1995) Structure 3, 1367-1377]. In order to investigate catalytic roles of
      the glutamic acid at the distal cavity, two horseradish peroxidase mutants were
      prepared, in which the distal His42 has been replaced by Glu (H42E) or Gln
      (H42Q). The formation rate of compound I in the H42E mutant was significantly
      greater than that for the H42Q mutant, indicating that the distal Glu can play a
      role as a general acid-base catalyst. However, the peroxidase activity of the
      H42E mutant was still lower, compared to that for native enzyme. On the basis of
      the CD, resonance Raman, and EPR spectra, it was suggested that the basicity of
      the distal Glu is lower than that of the distal His and the position of the
      distal Glu is not fixed at the optimal position as a catalytic amino acid
      residue, although no prominent structural changes around heme environment were
      detected. The less basicity and improper positioning of the distal Glu would
      destabilize the heme-H2O2-distal Glu ternary intermediate for the peroxidase
      reaction. Another characteristic feature in the mutants was the enhancement of
      the peroxygenase activity. Since the peroxygenase activity was remarkably
      enhanced in the H42E mutant, the distal Glu is also crucial to facilitate the
      peroxygenase activity as well as the enlarged distal cavity caused by the amino
      acid substitution. These observations indicate that the distal amino acid residue
      is essential for function of peroxidases and subtle conformational changes around
      the distal cavity would control the catalytic reactions in peroxidase.

PMID- 9245420
TI  - Carboxylate ions are strong allosteric ligands for the HisB10 sites of the R
      state insulin hexamer.
AB  - The insulin hexamer is an allosteric protein which displays positive and negative
      cooperativity and half-site reactivity that is modulated by strong homotropic and
      heterotropic ligand binding interactions at two different loci. These loci
      consist of phenolic pockets situated on the dimer-dimer interfaces of T-R and R-R
      subunit pairs and of anion sites comprising the HisB10 metal ion sites of the R3
      units of the T3R3 and R6 states. In this study, we show that suitably tailored
      organic carboxylates are strong allosteric effectors with relatively high
      affinities for the R-state HisB10 metal sites. Methods of quantifying the
      relative affinities of ligands for these sites in both Co(II)- and Zn(II)
      substituted insulin hexamers are presented. These analyses show that, in addition
      to the electron density on the ion, the carboxylate affinity is influenced by
      polar, nonpolar, and hydrophobic interactions between substituents on the
      carboxylate and the amphipathic protein surface of the narrow tunnel which
      controls ligand access to the metal ion. Since the binding of anions to the
      HisB10 site makes a critically important contribution to the stability of the
      T3R3 and R6 forms of the insulin hexamer, the design of high-affinity ligands
      with a carboxylate donor for coordination to the metal ion provides an
      opportunity for constructing insulin formulations with improved pharmaceutical
      properties.

PMID- 9245422
TI  - Circular dichroism of denatured barstar suggests residual structure,.
AB  - The circular dichroism (CD) spectrum of the denatured state of barstar has been
      analyzed as a function of urea and temperature. The near- and far-UV CD spectra
      change very rapidly in magnitude and shape with increasing temperature, unlike
      those of native protein, suggesting the presence of residual structure that
      changes with denaturing conditions. The effect of mutations indicates that there
      is residual structure in helix1 of the protein, consistent with NMR data. The
      changes in CD with conditions are consistent with the denatured state being a
      mixture of conformations of similar energy.

PMID- 9245423
TI  - The homodimeric form of glycine N-methyltransferase acts as a polycyclic aromatic
      hydrocarbon-binding receptor.
AB  - In the rat, cytochrome P4501A1 gene expression is thought to be regulated by
      several trans-acting factors including the 4S polycyclic aromatic hydrocarbon
      (PAH)-binding protein, which was recently identified as glycine N
      methyltransferase [Raha, A., Wagner, C., MacDonald, R. G., and Bresnick, E.
      (1994) J. Biol. Chem. 268, 5750-5756]. Glycine N-methyltransferase (GNMT) is one
      of those unique proteins which exhibit diversity in function. Different subunit
      configurations are involved in its enzymatic role as a methyltransferase and as
      PAH-binding receptor. Here we report a systematic study of the oligomeric state
      of GNMT in the presence of benzo[a]pyrene (B[a]P) in vivo and in vitro. We have
      used chemical cross-linking and denaturing polyacrylamide gel electrophoresis to
      show that the B[a]P-binding unit of GNMT is a homodimer. We recently reported
      that phosphorylation is involved in the interaction of B[a]P with the 4S PAH
      binding protein [Bhat, R., Weaver, J. A., Wagner, C., Bodwell, J. E., and
      Bresnick, E. (1996) J. Biol. Chem. 271, 32551-32556]. In the present study, this
      observation has been amplified by using bacterially expressed GNMT, which was
      post-translationally modified by a reticulocyte lysate and ATP-generating system.
      This modification was also accompanied by the formation of homodimers in the
      presence of B[a]P. These results indicate that post-translational modification is
      involved in determining the final configuration, i.e., dimeric form, of GNMT
      which then acts as a PAH-binding receptor.

PMID- 9245424
TI  - Effects of sulfhydryl modification reagents on the kinase activity of the
      epidermal growth factor receptor.
AB  - Earlier reports have indicated that epidermal growth factor (EGF) receptor
      autophosphorylation, thought to be a key step in receptor transmembrane
      signaling, can be inactivated with the relatively sulfhydryl-specific reagent N
      ethylmaleimide (NEM); however, no Cys residue has been implicated in the
      catalytic mechanism of the kinase. In an effort to address the mechanism of
      inhibition by NEM, we have investigated effects of several sulfhydryl-modifying
      reagents on EGF receptor autophosphorylation and on the kinase activity of the
      receptor toward an exogenous peptide substrate. Kinase activity is relatively
      insensitive to iodoacetic acid (IAAcid) and iodoacetamide (IAAmide), though
      IAAmide-treated receptor displays a higher Km(app) with respect to ATP, relative
      to untreated receptor. In contrast, even low concentrations of the very specific
      sulfhydryl reagent p-chloromercuribenzoic acid (PCMB) inactivate the receptor
      kinase. Pretreatment of the receptor with IAAmide, but not IAAcid, provides
      substantial protection of the kinase from subsequent treatment with NEM and a
      degree of protection from subsequent treatment with PCMB. Further, inactivation
      by NEM, and to a lesser extent PCMB, is inhibited by coincubation of the receptor
      with the hydrolysis-resistant ATP analog AMP-PNP. The protective effect of
      IAAmide from inactivation by NEM is also lost when AMP-PNP is present during the
      IAAmide treatment. Pretreatment of receptor with IAAcid has no effect on
      subsequent modification by IAAmide. These results, taken together, suggest that
      NEM, PCMB, and IAAmide, but not IAAcid, modify a Cys residue of the EGF receptor
      kinase that is inaccessible when nucleotide is bound. Modification of this
      residue by a bulky reagent (NEM, PCMB) inactivates the kinase by a steric
      mechanism, while modification with the smaller reagent (IAAmide) results in an
      active enzyme with altered affinity for ATP. Further, PCMB appears to react with
      an additional Cys residue (or residues), also resulting in steric inactivation.

PMID- 9245425
TI  - Optimizing the metal binding parameters of an EF-hand-like calcium chelation
      loop: coordinating side chains play a more important tuning role than chelation
      loop flexibility.
AB  - In calcium signaling pathways regulated by the EF-hand Ca2+ binding motif, proper
      regulation requires that the equilibrium and kinetics of Ca2+ binding to the EF
      hand chelation loop be precisely optimized for each physiological application.
      Studies of small-molecule organic chelators have shown that metal binding
      parameters can be tuned both by the nature of the coordinating ligands and by the
      structural framework to which these ligands are attached. By analogy, the present
      study tests the relative importance of (i) coordinating side chains and (ii)
      backbone torsion angle constraints to the tuning of an EF-hand-like Ca2+
      chelation loop. A series of engineered chelation loops are generated by modifying
      Ca2+ binding site of the Escherichia coli galactose binding protein. The
      resulting loops, each containing an altered coordinating side chain or a Gly
      substitution, are compared with respect to their metal binding affinities,
      specificities, and dissociation kinetics. The Gly variants examined include
      substitutions which eliminate or introduce a Gly at each of the nine chelation
      loop positions. The results reveal that Gly is not tolerated at loop positions 1,
      3, 5, or 8 or at the external coordinating position, where the removal of a key
      coordinating or hydrophobic side chain destabilizes the protein. In contrast, Gly
      residues at loop positions 2, 4, 6, and 7, none of which is required for side
      chain coordination, have little effect on Ca2+ affinity and the ability to
      discriminate between cations of different size and charge. Kinetic measurements
      show that some of these Gly residues measurably alter the rates of metal ion
      association and dissociation, but in each case the two rates are changed by
      approximately the same factor so that the effects on equilibrium are minor.
      Overall, Gly residues yield surprisingly small effects at loop positions 2, 4, 6,
      and 7, especially when compared to the larger equilibrium and kinetic effects
      observed for coordinating side chain substitutions. It follows that the conserved
      Gly at position 6 is not required for Ca2+ binding and that constraints on the
      backbone torsion angles at the non-coordinating side chain positions 2, 4, 6, and
      7 play a relatively minor role in tuning metal binding parameters. Instead,
      specific coordinating side chains optimize the metal binding parameters of the
      GBP chelation loop for its protein context and biological application.

PMID- 9245427
TI  - A new type of hairpin ribozyme consisting of three domains.
AB  - We have constructed a new hairpin ribozyme with three stem-loop domains. In the
      ribozyme, another domain (domain I') was connected to the 3'-end of domain II of
      the parent hairpin ribozyme, and the new ribozyme can be trimmed after
      transcription from the DNA template using T7 RNA polymerase. Since a mutant
      ribozyme containing a substitution at the essential base in domain I' lacked the
      3'-trimming reaction, the autoprocessing activity was proved to be derived from
      the catalytic reaction, similar to the wild-type ribozyme. Furthermore, the
      structure of the cleavage site from the self-trimming reaction was identified as
      a 2',3'-cyclic phosphate, which is the same as that of the wild-type. The
      processed ribozyme was designed to cleave an external substrate RNA derived from
      the mRNA of the human inducible nitric oxide synthase and was proved to cleave at
      the expected, unique site. The hairpin ribozyme containing the three-domains
      exhibited the 3'-self-trimming activity even in a runoff transcription reaction
      from the plasmid harboring the ribozyme gene with the three domains. The new type
      of hairpin ribozyme thus obtained has three stem-loop domains and is able to act
      as a catalytic RNA for both cis and trans cleavage. These ribozymes are of
      interest from the point of the structure-function relationship of the hairpin
      ribozyme and provide an important insight into over understanding of the role of
      the domain-domain interaction in the catalytic activity.

PMID- 9245426
TI  - Trapping and characterization of the reaction intermediate in cyclodextrin
      glycosyltransferase by use of activated substrates and a mutant enzyme.
AB  - Cyclodextrin glycosyltransferases (CGTases) catalyze the degradation of starch
      into linear or cyclic oligosaccharides via a glycosyl transfer reaction occurring
      with retention of anomeric configuration. They are also shown to catalyze the
      coupling of maltooligosaccharyl fluorides. Reaction is thought to proceed via a
      double-displacement mechanism involving a covalent glycosyl-enzyme intermediate.
      This intermediate can be trapped by use of 4-deoxymaltotriosyl alpha-fluoride
      (4DG3alphaF). This substrate contains a good leaving group, fluoride, thus
      facilitating formation of the intermediate, but cannot undergo the
      transglycosylation step since the nucleophilic hydroxyl group at the 4-position
      is missing. When 4DG3alphaF was reacted with wild-type CGTase (Bacillus circulans
      251), it was found to be a slow substrate (kcat = 2 s-1) compared with the parent
      glycosyl fluoride, maltotriosyl alpha-fluoride (kcat = 275 s-1). Unfortunately, a
      competing hydrolysis reaction reduces the lifetime of the intermediate precluding
      its trapping and identification. However, when 4DG3alphaF was used in the
      presence of the presumed acid/base catalyst mutant Glu257Gln, the intermediate
      could be trapped and analyzed because the first step remained fast while the
      second step was further slowed (kcat = 0.6 s-1). Two glycosylated peptides were
      identified in a proteolytic digest of the inhibited enzyme by means of neutral
      loss tandem mass spectrometry. Edman sequencing of these labeled peptides allowed
      identification of Asp229 as the catalytic nucleophile and provided evidence for a
      covalent intermediate in CGTase. Asp229 is found to be conserved in all members
      of the family 13 glycosyl transferases.

PMID- 9245428
TI  - Construction and characterization of monomeric tryptophan repressor: a model for
      an early intermediate in the folding of a dimeric protein.
AB  - Tryptophan repressor (TR) from Escherichia coli is a homodimer whose highly
      helical subunits intertwine in a complex fashion. A monomeric version of Trp
      repressor has been constructed by introducing a pair of polar amino acids at the
      hydrophobic dimer interface. Analytical ultracentrifugation was used to show that
      the replacement of leucine at position 39 with glutamic acid results in a
      monomer/dimer equilibrium whose dissociation constant is 1.11 x 10(-)4 M at 25
      degrees C and pH 7.6. Tryptophan fluorescence, both near- and far-UV circular
      dichroism, and NMR spectroscopies demonstrated that, at the micromolar
      concentrations where the monomer predominates, secondary and tertiary structure
      are present. Hydrophobic dye-binding experiments showed that nonpolar surface is
      accessible in the monomeric form. The urea-induced equilibrium unfolding of
      monomeric L39E TR was monitored by circular dichroism, fluorescence, and
      absorbance spectroscopies. Coincident transitions show that the urea denaturation
      process follows a simple two-state model involving monomeric native and unfolded
      forms. The free energy at standard state in the absence of denaturant was
      estimated to be 2.37 +/- 0.15 kcal mol-1, and the sensitivity of the unfolding
      transition to denaturant, the m value, was 0.86 +/- 0.04 kcal mol-1 M(urea)-1 at
      pH 7.6 and 25 degrees C. The thermal denaturation transition occurred over a
      broad temperature range, suggesting either that the enthalpy change is small or
      that intermediates may exist. Kinetic studies showed that both the refolding and
      unfolding of the monomer were complete in the mixing dead time of stopped-flow CD
      and fluorescence spectroscopy, 5 ms. These structural, thermodynamic, and kinetic
      results are very similar to those previously reported for an early, monomeric
      intermediate in the folding of the wild-type TR dimer [Mann, C. J., & Matthews,
      C. R. (1993) Biochemistry 32, 5282-5290]. The construction of a stable, monomeric
      form of TR that strongly resembles a transient folding intermediate should
      provide useful insights into the nature of the early events in the folding of TR.

PMID- 9245429
TI  - Sodium Green as a potential probe for intracellular sodium imaging based on
      fluorescence lifetime.
AB  - We characterized the use of the fluorescent probe Sodium Green for measurements
      of intracellular free sodium using frequency-domain, phase-modulation
      fluorometry. The intensity decays were found to be strongly Na+ dependent, with
      mean lifetime increasing from 1.13 ns in the absence of Na+ to 2.39 ns in the
      presence of 140 mM Na+. Detailed analysis of the intensity decays in the presence
      of Na+ and K+ in the concentration range from 0 to 500 mM is provided. Sodium
      sensing using data measured at a single modulation frequency is described. Phase
      and modulation data showed high sensitivity to Na+ and substantially lower
      sensitivity to K+. Additionally, exposure of Sodium Green to intense illumination
      indicated that Sodium Green is much more photostable than its precursor,
      fluorescein. These results indicate that lifetime-based measurements with Sodium
      Green can be used for imaging of intracellular free [Na+] in the range from about
      0.5 to 50 mM with high accuracy.

PMID- 9245430
TI  - The release and detection of endotoxin from liposomes.
AB  - Incorporation of lipopolysaccharide (LPS) into liposomes dramatically reduces its
      ability to coagulate Limulus amebocyte lysate (LAL). The coagulation of LAL is
      commonly used to signal the presence of endotoxin in vitro. This study
      demonstrates a simple method to release masked endotoxin from liposomal
      dispersions using moderate amounts of detergent to form mixed micelles containing
      lipid, detergent, and LPS. Several parameters were found to affect the degree of
      liposome solubilization and/or the sensitivity of the LAL assay. These included
      detergent type and concentration, temperature for solubilization, lipid
      composition, liposome morphology, and time for test incubation. The nonionic
      detergent polyoxyethylene 10 lauryl ether (C12E10) proved to be unique in its
      ability to solubilize liposomes and minimally interfere with endotoxin detection.
      The LAL endotoxin detection limit for samples dispersed in C12E10 varied with the
      phospholipid component; the sensitivity decreased in the order DSPC > DPPC = EPC
      >> DMPC. Cholesterol lowered the solubility limit of the liposomes, but did not
      appear to affect the LAL assay sensitivity once the liposomes were completely
      solubilized. The presence of negatively charged phospholipids, DSPG and Pops,
      also lowered the solubility limit. Pops, but not DSPG, at 10 mol% further
      decreased the LAL endotoxin detection limit. This detergent-solubilization method
      should be useful in liposomal LPS immunological studies or in other situations
      where accurate determination of endotoxin concentration is important.

PMID- 9245431
TI  - Qualitative and quantitative analysis of DNA fragmentation using digital imaging.
AB  - Apoptosis is an important and common pathway of cellular death. Differentiation
      from cellular necrosis and quantitation of apoptosis within the milieu of
      necrosis are analytical challenges. We describe the use of the RIT120 digital
      imaging software package for quantitative and qualitative analysis of apoptotic
      DNA ladders induced by a variety of agents, such as serum, tumor necrosis factor
      alpha, transforming growth factor-beta1, and nitric oxide. Autoradiographs of DNA
      ladders are densitometrically scanned to yield a set of curves with peaks
      corresponding to specific DNA fragments, thereby allowing quantitative
      subtraction of concurrent DNA degradation from necrotic death. Integration of the
      areas specifically under the peaks yields a quantitative measure of apoptosis. We
      provide a useful, rapid, and objective means to quantitate apoptosis, using
      relatively inexpensive hardware and software.

PMID- 9245432
TI  - Identification of proteins by matrix-assisted laser desorption ionization-mass
      spectrometry following in-gel digestion in low-salt, nonvolatile buffer and
      simplified peptide recovery.
AB  - Matrix-assisted laser desorption ionization-mass spectrometry is an efficient
      analytical method for large-scale identification of proteins separated by two
      dimensional polyacrylamide gel electrophoresis. Following in-gel digestion, the
      salt present in the peptide extracts is usually removed by chromatography prior
      to analysis. Desalting is a labor-intensive and time-consuming step, limiting the
      total number of samples that can be processed daily. We improved the daily sample
      output by performing the in-gel protein digestion in low-salt, nonvolatile buffer
      and simplifying the recovery of the generated peptides, collecting them in a
      small volume by sonication. This technique is routinely used for identification
      of proteins of Haemophilus influenzae and human brain. The methodology described
      facilitates the analytical process and allows the analysis of hundreds of
      proteins per day. Furthermore, it represents an essential step toward process
      automation.

PMID- 9245433
TI  - Enzymatic treatment to eliminate the extracellular ATP for improving the
      detectability of bacterial intracellular ATP.
AB  - A novel and effective treatment of biological samples with a combination of
      adenosine phosphate deaminase and apyrase was developed for reducing
      extracellular ATP, which has been a major problem encountered in improving the
      sensitivity of assays for intracellular ATP by the firefly luciferin-luciferase
      (L-L) method. Under the enzymatic reaction conditions, ATP and the related
      adenosine derivatives were converted to IMP, which are not active to the L-L
      system. In the model system (3.2 x 10(-8) M ATP in 1% yeast extract solution) the
      treatment with adenosine phosphate deaminase resulted in the reduction of ATP to
      1.3 x 10(-11) M, and the concomitant use of apyrase lowered the concentration to
      3.3 x 10(-13) M. The treatment (0.05 U/ml of adenosine phosphate deaminase and
      apyrase) was applied to the detection of bacteria in broth by the L-L method,
      affording the detection of 42 colony-forming unit (CFU)/ml of Escherichia coli
      and 10 CFU/ml of Staphylococcus aureus in the broth.

PMID- 9245434
TI  - Stability enhancement for peptide analysis by electrospray using the triple
      quadrupole mass spectrometer.
AB  - Electrospray ionization sources, used with triple quadrupole mass spectrometers
      from PE/Sciex (API III+), Micromass (Quattro II), and Finnigan (TSQ 7000), were
      modified with a 35-gauge stainless steel needle. The dimensions of the needle
      were 63 microm i.d. by 145 microm o.d. with variable length, depending on the
      specific instrument. This modification led to enhanced signal stability, improved
      signal/noise ratios, and lowered sample consumption for a wide range of peptides.
      Stable baselines were observed with flow rates in the range of 50 nL/min to 5
      microL/min. An alternative design, based on a metal wire housed within a fused
      silica capillary, led to the most stable signals of all during infusion, but
      caused excessive peak broadening with capillary chromatography. The Finnigan
      interface was further modified with an external postcolumn addition tee, used in
      conjunction with capillary liquid chromatography columns of 30 and 50 microm
      internal diameter. The best results with the modified Finnigan interface were
      acquired using the 50-microm column at a flow rate of 150 to 200 nL/min.

PMID- 9245435
TI  - Isolation of lamellar aggregates of the light-harvesting chlorophyll a/b protein
      complex of photosystem II with long-range chiral order and structural
      flexibility.
AB  - Isolation of LHCII, the light-harvesting chlorophyll a/b complex of photosystem
      II, based on the procedure described by Krupa et al. (1987, Plant Physiol. 84, 19
      24), was optimized for obtaining purified lamellar aggregates with long-range
      chiral order and structural flexibility (the capability of undergoing light
      induced reversible structural changes). By varying the concentration of the
      detergent Triton X-100 for the solubilization of thylakoid membranes, we obtained
      four types of LHCII aggregates: (i) With low detergent concentration, < or = 0.6%
      (v/v), the aggregates contained lipids in high amount. These preparations with
      Chl a/b ratios of about 1.4 contained minor antenna complexes with a fingerprint
      of an additional CD band at (+) 505 nm; they formed disordered lamellae and
      exhibited no or weak psi-type CD bands (psi, polymerization- or salt-induced),
      which did not possess the ability to undergo light-induced changes (deltaCD).
      (ii) At the optimal concentration, around 0.7 +/- 0.1% (v/v), the detergent
      removed some lipids and most of the minor complexes, and the Chl a/b ratio
      dropped to 1.0-1.1. LHCII formed loosely stacked two-dimensional lamellae which
      exhibited psi-type CD bands and large light-induced reversible structural changes
      (deltaCD). (iii) At detergent concentration above the optimum, around 0.8-1%
      (v/v), the lipid content of LHCII decreased and minor complexes could not be
      detected. LHCII formed disordered aggregates and showed neither psi-type CD nor
      deltaCD. (iv) High concentrations (> or = 1.1% (v/v)) Triton X-100 led to very
      pure but largely delipidated samples assembled into tightly stacked three
      dimensional lamellar structures with intense psi-type CD but no deltaCD.

PMID- 9245436
TI  - Chemical synthesis of 4-trifluoromethylumbelliferyl-alpha-D-N-acetylneuraminic
      acid glycoside and its use for the fluorometric detection of poorly expressed
      natural and recombinant sialidases.
AB  - When compared to bacterial or viral sialidases, eukaryotic sialidases are
      expressed at lower levels and frequently show poor specific activities. The
      identification and characterization of sialidases from eukaryotes have been
      slowed down due to the limited sensitivity of available sialidase substrates.
      Therefore, we chemically synthesized a fluorogenic compound, 4
      trifluoromethylumbelliferyl-alpha-D-N-acetylneuraminic acid (CF3MU-Neu5Ac), and
      tested its use as a substrate for eight different sialidases, including enzymes
      from viral, bacterial, and eukaryotic sources. Kinetic analysis revealed CF3MU
      Neu5Ac to be a very sensitive sialidase substrate. Furthermore, this substance
      proves to be perfectly suitable for the in vivo examination of sialidases and for
      the detection of recombinant sialidase by means of expression cloning.

PMID- 9245437
TI  - Nonisotopic quantitative analysis of protein-DNA interactions at equilibrium.
AB  - Two versions of an enzyme-linked immunosorbent assay-type method to quantify
      protein-DNA interactions at equilibrium were developed. The first variant
      comprised immobilization of DNA-binding protein on microtiter plates, incubation
      with biotinylated DNA, and tagging of bound DNA with streptavidin- and biotin
      substituted horseradish peroxidase. In the second version, biotinylated DNA was
      immobilized on streptavidin-substituted microtiter plates, incubated with DNA
      binding protein, and bound protein was quantified with specific antibodies. To
      illustrate the method, the interaction of a fusion protein between glutathione-S
      transferase and the DNA-binding domain of the helicase-like transcription factor
      with its cis-element (the B box of the plasminogen activator inhibitor-1
      promoter) was determined with both versions: a 1:1 stoichiometric interaction
      with an equilibrium dissociation constant (Kd) of 1 nM was found, which is
      similar to the value determined by electrophoretic mobility shift assay,
      demonstrating the validity of the assays.

PMID- 9245438
TI  - Classification of Vibrio vulnificus strains by the carbohydrate composition of
      their capsular polysaccharides.
AB  - Pathogenic bacteria are often classified on the basis of the complex
      polysaccharides found on the surface, usually capsular polysaccharides or
      lipopolysaccharides. It is common in clinical practice to use reactivity with
      antisera specific to the various cell surface carbohydrates for this purpose. In
      this work, we describe a chemotyping method for bacterial capsular
      polysaccharides which is based on a carbohydrate analysis of an acid hydrolysate
      of the capsule. High-performance anion-exchange chromatography at high pH (HPAE)
      with electrochemical detection, which is used for analysis of the hydrolysate,
      shows preferential sensitivity for sugars. A single acid hydrolysis condition is
      chosen for screening a large collection of bacterial isolates and a computerized
      autosampler is used to make possible a large number of rapid analyses. This
      procedure does not yield a quantitative carbohydrate analysis for the sample but
      produces a fingerprint which can be used to discriminate among isolates which
      have different capsular polysaccharide structures. The procedure has been applied
      to a collection of 120 isolates of Vibrio vulnificus, a water-born species common
      in shellfish which causes septicemia in immunocompromised individuals, most often
      from eating of raw oysters. The collection of bacterial isolates includes strains
      from both clinical cases of septicemia and from such environmental sources such
      as sea water, sediments, and shellfish. Our results show that a number of unusual
      sugars including many amino sugars are found in these polysaccharides and that a
      wide variety of capsular carbotypes in V. vulnificus may be readily distinguished
      by the HPAE fingerprint.

PMID- 9245439
TI  - Entropies of redox reactions between proteins and mediators: the temperature
      dependence of reversible electrode potentials in aqueous buffers.
AB  - The temperature dependencies of the reversible electrode potentials for a number
      of charge transfer reactions of redox mediators were used to evaluate the
      corresponding charge transfer entropies in Tris-HCl (pH 8) buffer. The redox
      mediator thermodynamic data, along with reaction enthalpy data for mediator redox
      protein electron transfer, were used to evaluate the charge transfer entropy for
      the cytochrome c redox couple [(cytc)ox/(cytc)red] in Tris-HCl (pH 8) buffer and
      were found to be equal to -16 cal/degrees K mol. Reversible electrode potentials
      at 298 degrees K for the redox mediator half-reactions were observed to vary from
      -528 to +657 mV (vs NHE). Charge transfer entropies were observed to depend upon
      the structure of the redox mediators and to vary from -13.8 to -29.7 cal/degrees
      K mol for a closely related series of organic dications (viologens) and a value
      of -43.6 cal/degrees K mol was observed for the [Fe(CN)6]3-/[Fe(CN)6]4- couple
      under the same conditions. A procedure for determining charge transfer entropies
      of protein redox couples which cannot be studied by direct electrochemical
      methods is outlined. The factors contributing to the magnitude of the charge
      transfer entropies are discussed.

PMID- 9245440
TI  - Manual manufacturing of oligonucleotide, DNA, and protein microchips.
AB  - A simple procedure for manufacturing microchips containing various gel
      immobilized compounds is described. A gel photopolymerization technique is
      introduced to produce micromatrices of polyacrylamide gel pads (25 x 25 x 20
      microm and larger) separated by a hydrophobic glass surface. A pin device for the
      manual application of a compound in solution onto the activated polyacrylamide
      gel pad for immobilization is described. Oligonucleotide, DNA, and protein
      microchips have been produced by this method and tested by hybridization and
      immunoanalysis monitored with a fluorescence microscope. The effect of the
      lengths of the immobilized oligonucleotides and the hybridized RNA and DNA on
      hybridization of the oligonucleotide microchips was evaluated. This method can
      also be used for manufacturing microchips containing a variety of other
      compounds.

PMID- 9245441
TI  - Vibrational circular dichroism spectra of proteins in the amide III region:
      measurement and correlation of bandshape to secondary structure.
AB  - Vibrational circular dichroism (VCD) spectra have been measured for 23 globular
      proteins dissolved in H2O/phosphate buffer over the 1400 to 1100 cm(-1) region
      which encompasses the amide III mode. Spectral responses characteristic of the
      dominant secondary structure type were found as broad features at approximately
      1300 cm(-1), with the extreme forms having positive VCD for highly helical
      proteins and negative VCD for highly sheet-containing proteins. Quantitative
      correlation with secondary structure was carried out using previously developed
      factor analysis and restricted multiple regression (FA/RMR) techniques. Since the
      absorbance intensity of the amide III mode is difficult to determine due to
      overlap with other transitions, an alternative, absolute intensity-independent,
      simple structural analysis method was used. A linear regression was developed
      between the fractional components of secondary structure for the protein set and
      the overlap integrals of the normalized spectra from the set with that of a
      selected protein. The results of this simple method are quite comparable to those
      of the FA/ RMR approach for analysis with amide III VCD. On the other hand, test
      calculations with the new method when used with electronic CD spectra are not as
      good as FA/RMR due to its more intensity-dependent relationship with secondary
      structure.

PMID- 9245442
TI  - A versatile microassay for elastase using succinylated elastin.
AB  - We have developed a rapid, versatile, and sensitive elastase assay that is based
      on the measurement of primary amines that are exposed due to enzymatic
      degradation of proteins, using succinylated elastin as the substrate for
      elastase. After incubation with elastase the degree of digestion is determined
      with trinitrobenzene sulfonic acid. The assay is rapid and sensitive, detecting
      elastase down to 1 ng/ml, and is linear up to enzyme concentrations of 10
      microg/ml. The assay is carried out in microtiter plate wells and therefore
      offers the potential for assaying numerous samples of small volume. The use of
      succinylated elastin shows specificity for elastase over the control protease,
      trypsin. This assay is also versatile because it can be applied to samples such
      as cell culture supernatants, blood plasma, tissue biopsies, and tissue
      homogenates.

PMID- 9245443
TI  - Direct and indirect methods for molar-mass analysis of fragments of the capsular
      polysaccharide of Haemophilus influenzae type b.
AB  - Two methods are described for direct molar-mass measurement of low-molar-mass
      fragments obtained by oxidative cleavage of the capsular polysaccharide of
      Haemophilus influenzae type b. Absolute molar masses were determined by size
      exclusion chromatography (SEC) with detection by multiangle laser-light
      scattering photometry (MALLS) and differential refractometry (RI). The end-group
      structure of the polysaccharide fragments allowed the direct measurement of
      average chain length by quantitative 1H NMR, from which molar masses were
      derived. Variation between the molar masses obtained by the two methods ranged
      from 5 to 7%. When molar masses estimated by indirect methods were compared to
      SEC-MALLS/RI data, significant deviations were observed. Analysis by SEC with
      secondary calibration with dextran standards gave molar masses that exceeded the
      SEC-MALLS/RI data by as much as 2.5-fold. Molar masses estimated by a combination
      of colorimetric assays varied from the SEC-MALLS/RI data by as much as 50%. These
      results demonstrated the applicability and superior accuracy of the direct
      methods of molar-mass determination of the polysaccharide fragments.

PMID- 9245444
TI  - A new ultrasensitive scanning calorimeter.
AB  - A new ultrasensitive differential scanning calorimeter is described, having a
      number of novel features arising from integration between hardware and software.
      It is capable of high performance in either a scanning or isothermal mode of
      operation. Upscanning is carried out adiabatically while downscanning is
      nonadiabatic. By using software-controlled signals sent continuously to
      appropriate hardware devices, it is possible to improve adiabaticity and
      constancy of scan rate through use of empirical prerun information stored in
      memory rather than by using feedback systems which respond in real time and
      generate thermal noise. Also, instrument response time is software-selectable,
      maximizing performance for both slow- and fast-transient systems. While these and
      other sophisticated functionalities have been introduced into the instrument to
      improve performance and data analysis, they are virtually invisible and add no
      additional complexities into operation of the instrument. Noise and baseline
      repeatability are an order of magnitude better than published raw data from other
      instruments so that high-quality results can be obtained on protein solutions,
      for example, using as little as 50 microg of protein in the sample cell.

PMID- 9245445
TI  - Separation of oligo/polymers of 5-N-acetylneuraminic acid, 5-N-glycolylneuraminic
      acid, and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid by high-performance
      anion-exchange chromatography with pulsed amperometric detector.
AB  - A sensitive and efficient method to analyze oligo/ poly-sialic acids containing
      alpha2-8-linked 5-N-acetylneuraminic acid (Neu5Ac), 5-N-glycolylneuraminic acid
      (Neu5Gc), and deaminated neuraminic acid (KDN) using high-performance anion
      exchange chromatography (HPAEC) with a pulsed amperometric detector (PAD-2) has
      been developed. Using a CarboPac PA-100 column and sodium nitrate as the pushing
      agent, polymers in colominic acid with degree of polymerization (DP) up to 80
      were separated in 68 min. A similar DP-based resolution was also obtained on a
      CarboPac PA-1 column. The elution ladders of the Neu5Ac, Neu5Gc, and KDN series
      were sufficiently different to be used as diagnostic indices. This technique was
      applied to identification of the sialic acid components in a
      polysialoglycoprotein (PSGP) sample as well as monitoring the oligo/poly-KDN
      containing fractions during the purification of KDN-containing glycoprotein (KDN
      gp). The maximum DPs of oligo-Neu5Gc and oligo-KDN that can be detected in PSGP
      and KDN-gp hydrolysates were 11 and 8, respectively. The high sensitivity of this
      method was demonstrated by the quantification of Neu5Ac oligomers. Distributions
      of the monomer and oligo/polymers in the acid and enzymatic hydrolysates of
      colominic acid and PSGP under different conditions were also studied.

PMID- 9245446
TI  - Spectrophotometric assay of D-aspartate and D-glutamate using D-aspartate oxidase
      with malate dehydrogenase and glutamate dehydrogenase.

PMID- 9245447
TI  - Colorimetric assay for substrates of NADP+-dependent dehydrogenases based on
      reduction of a tetrazolium dye to its soluble formazan.

PMID- 9245448
TI  - Peptide nucleic acid-mediated polymerase chain reaction clamping allows allelic
      allocation of CYP1A1 mutations.

PMID- 9245449
TI  - Concentration of dilute protein solutions prior to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis.

PMID- 9245450
TI  - Europium labeling of natural and synthetic glycopeptides.

PMID- 9245451
TI  - An efficient method for cloning in-frame fusion protein genes.

PMID- 9245452
TI  - Attention, Awareness, and the Triangular Circuit
AB  - It is proposed that attention to an object requires the simultaneous activity of
      three brain regions that are interconnected by a triangular circuit. The regions
      are the cortical site of attentional expression, the thalamic enhancement
      structure, and the prefrontal area of control. It is also proposed that awareness
      of an object requires the additional component of attention directed to a
      representation of the self. The expression of attention to a self-representation
      may involve activations of cortical sites corresponding to the body landscape
      and/or verbal-based memories of autobiographical episodes. As in the case of
      attention to objects, attention to the self is presumed to involve a triangular
      circuit. The proposed triangular circuit of attention is shown to be generally
      consistent with current knowledge of brain structures and with data from a broad
      range of experiments concerned with the functions of neurons in these structures.

PMID- 9245453
TI  - Constraints on Awareness, Attention, Processing, and Memory: Some Recent
      Investigations with Ignored Speech
AB  - We discuss potential benefits of research in which attention is directed toward
      or away from a spoken channel and measures of the allocation of attention are
      used. This type of research is relevant to at least two basic, still-unresolved
      issues in cognitive psychology: (a) the extent to which unattended information is
      processed and (b) the extent to which unattended information that is processed
      can later be remembered. Four recent studies of this type that address these
      questions in various ways (Cowan, Lichty, & Grove, 1990; Wood & Cowan, 1995a,b;
      Wood, Stadler & Cowan, in press) are reviewed as illustrations. We conclude from
      these studies that (a) unattended information appears to be partially processed
      automatically, though attention enhances the processing considerably, and (b) the
      unattended information that is processed may not be retrievable in direct or many
      indirect memory tasks, though it remains possible that there is an automatically
      stored memory trace (e.g., one that could produce semantic priming).

PMID- 9245454
TI  - Attention and Semantic Priming: A Review of Prime Task Effects
AB  - The single-word semantic priming paradigm is a tool for investigating how and
      when word meaning (semantic) activation occurs during visual word recognition.
      The prime task effect refers to the elimination of the typically robust semantic
      priming effect by a nonsemantic prime task (e.g., subjects search the prime word
      for a letter). The purpose of this paper is to provide a tutorial review of the
      literature examining the prime task effect. Understanding the nature of this
      effect has implications for delineating how selective attention modulates
      evidence for semantic activation during word reading. These implications are
      outlined. Additionally, speculations for how these issues of selective attention
      relate to awareness are offered.

PMID- 9245455
TI  - Parallels between Perception without Attention and Perception without Awareness
AB  - Do studies of perception without awareness and studies of perception without
      attention address a similar underlying concept of awareness? To answer this
      question, we compared qualitative differences in performance across variations in
      stimulus quality (i.e., short vs. long prime-mask stimulus onset asynchrony) with
      qualitative differences in performance across variations in the direction of
      attention (i.e., focused vs. divided). The qualitative differences were based on
      three different phenomena: Stroop priming, false recognition, and exclusion
      failure. In all cases, variations in stimulus quality and variations in the
      direction of attention led to parallel findings. These results suggest that
      perception with and without awareness and perception with and without attention
      are equivalent ways of describing the same underlying process distinction.

PMID- 9245456
TI  - What Is It Like to Be a Patient with Apperceptive Agnosia?
AB  - Neuropsychological deficits have been widely used to elucidate normal cognitive
      functioning. Can patients with such deficits also be used to understand conscious
      visual experience? In this paper, we ask what it would be like to be a patient
      with apperceptive agnosia (a deficit in object recognition). Philosophical
      analyses of such questions have suggested that subjectively experiencing what
      another person experiences would be impossible. Although such roadblocks into the
      conscious experience of others exist, the experimental study of both patients and
      neurologically normal subjects can be used to understand visual processing
      mechanisms. In order to understand the visual processes damaged in apperceptive
      agnosia, we first review this syndrome and present a case study of one such
      patient, patient J.W. We then review several theoretical accounts of apperceptive
      agnosia, and we conclude that studies of the patients themselves may not allow us
      to discriminate between the various explanations of the syndrome. To test these
      accounts, we have simulated apperceptive agnosia in neurologically normal
      subjects. The implications of our results for understanding both apperceptive
      agnosia and normal visual processing are discussed.

PMID- 9245457
TI  - Brain Mechanisms of Cognitive Skills
AB  - This article examines the anatomy and circuitry of skills that, like reading,
      calculating, recognizing, or remembering, are common abilities of humans. While
      the anatomical areas active are unique to each skill there are features common to
      all tasks. For example, all skills produce activation of a small number of widely
      separated neural areas that appear necessary to perform the task. These neural
      areas relate to internal codes that may not be observed by any external behavior
      nor be reportable by the performer. There is considerable plasticity to the
      performance of skills. Task components can be given priority through attention,
      which serves to increase activation of the relevant brain areas. Attention can
      also cause reactivation of sensory areas driven by input, but usually only after
      a delay. The threshold for activation for any area may be temporarily reduced by
      prior activation (priming or practice). Skill components requiring attention tend
      to cause interference resulting in the dual tasks effects and unified focus of
      attention described in many cognitive studies. Practice may change the size or
      number of brain areas involved and alter the pathways used by the skill. By
      combining cognitive and anatomical analyses, a more general picture of the nature
      of skill emerges.

PMID- 9245458
TI  - Inhibitory Tagging of Locations in the Blind Field of Hemianopic Patients
AB  - This study evaluated the potential contribution of extrageniculate visual
      pathways to oculomotor orienting reflexes in hemianopic patients. It tested
      whether extrageniculate pathways mediate inhibition of return (IOR)-a phenomenon
      characterized by slowed target detections at recently stimulated locations
      (Posner & Cohen, 1984). Because hemianopic subjects cannot overtly respond to
      stimuli presented within their hemianopic field, we utilized a spatial cueing
      paradigm that capitalized on the fact that IOR operates in spatiotopic
      coordinates. Subjects moved their eyes so that a cue and a target presented at
      the same spatial location were imaged successively onto blind and seeing portions
      of their retinas. One hemianopic patient showed a similar IOR effect from cues
      presented within both the seeing and the hemianopic fields. With a second
      hemianopic patient, only presentations of the cue to the subject's seeing field
      produced IOR. The explanation for this discrepancy is not evident. These
      observations highlight both the potential value and the pitfalls inherent in
      using "blindsight" as a window into human consciousness.

PMID- 9245459
TI  - Negative Priming, Attention, and Discriminating the Present from the Past
AB  - Priming effects have been used widely as a tool to study attentional processes.
      However, inferences regarding attention depend on how priming effects are
      interpreted. In the case of negative priming, an activation-based framework for
      interpreting priming suggests that attention inhibits the representation of prime
      distractors and that this inhibition is measured in performance to subsequent
      probes. Data summarized in this article point out that negative priming does not
      depend on selection of one of two primes and that attentional influences during
      retrieval play an important role in determining negative priming. Also, two
      experiments are described that demonstrate a correlation between priming effects
      and knowledge of the relation between primes and probes. We suggest that negative
      priming is not determined directly by a process of ignoring, but instead occurs
      because a repeated probe is less temporally distinct when ignored as a prime than
      when attended.

PMID- 9245460
TI  - Facilitatory or Inhibitory Nontarget Effects in the Location-Cuing Paradigm
AB  - The effect of nontargets on the identification of targets in the location-cuing
      paradigm was investigated in order to determine whether observers consistently
      allocate their attention to a validly cued location and whether the effect of
      nontargets is to facilitate or to inhibit performance. In four experiments, the
      effects of a single matching nontarget or a single nonmatching nontarget were
      compared. In each experiment, it was shown that observers consistently allocate
      their attention to a cued location when a precue appears and that performance is
      inhibited more by nonmatching nontargets in the display than it is facilitated by
      matching nontargets.

PMID- 9245461
TI  - Understanding Diverse Effects of Visual Attention with the VAP-Filters Metaphor
AB  - The Variable and Permeable Filters (VAP-Filters) metaphor is presented with an
      explanation of its advantages over other popular metaphors in accounting for
      attention effects in many different research paradigms. Research from
      laboratories of the author and others are discussed briefly and shown to result
      in diverse facilitatory and inhibitory attention effects on visual perception.
      All of these effects are consistent with the VAP-Filters metaphor.

PMID- 9245462
TI  - Some Essential Differences between Consciousness and Attention, Perception, and
      Working Memory
AB  - When "divided attention" methods were discovered in the 1950s their implications
      for conscious experience were not widely appreciated. Yet when people process
      competing streams of sensory input they show both selective processes and clear
      contrasts between conscious and unconscious events. This paper suggests that the
      term "attention" may be best applied to the selection and maintenance of
      conscious contents and distinguished from consciousness itself. This is
      consistent with common usage. The operational criteria for selective attention,
      defined in this way, are entirely different from those used to assess
      consciousness. To illustrate the scientific usefulness of the distinction it is
      applied to Posner's (1994) brain model of visual attention. It seems that
      features that are often attributed to attention-like limited capacity-may more
      accurately be viewed as properties of consciousness.

PMID- 9245463
TI  - The Phenomenology of Attention
AB  - The effect of attention on perceived brightness and contrast was investigated in
      eight experiments. Attention was manipulated by engaging observers in an
      attention-demanding concurrent task (letter detection) or by directing attention
      to a location with a peripheral cue. In all of the dual-task manipulations,
      attention reduced the variability of responses. However, attention did not affect
      the brightness of stimuli, nor did it affect the amount of simultaneous
      brightness contrast. Results with peripheral location cues were similar; however,
      the effect of attention in these experiments could be attributed to nonperceptual
      factors. The metaphorical "spotlight" of attention reduces observers' uncertainty
      about the brightness of a stimulus, but it does not "illuminate" in terms of
      brightness or contrast.

PMID- 9245464
TI  - Successive Approximations to an Adequate Model of Attention
AB  - Everybody knows the phenomena summarized with the term attention: concentration,
      focalization, limitation, selection, and intensification (see, e.g., James,
      1890/1950). The explanation of these phenomena is, however, a different matter.
      Problems easily arise with regard to what has to be explained and with regard to
      the style of explanation. A problem of the first kind is the "methodology of 'bad
      focus'": the explanation starts with and is fixated on an intuitively striking
      but nonessential behavioral feature or cognitive achievement. A problem of the
      second kind is a "virtus dormitiva" explanation: the explanation starts with
      emphasizing one aspect of the observed phenomena, the emphasized aspect receives
      an interesting and suggestive name, and that name with its connotations is used
      as a concept in the explanation. At the start of contemporary, behavior-based,
      information processing psychology, a virtus dormitiva explanation infiltrated the
      functional accounts of the phenomena of attention; the empirical observation that
      people show performance limitations was translated into the theoretical concept
      of a communication channel with a limited capacity. That limited capacity notion
      became the core concept in what can be called the standard theory of attention.
      This standard theory of attention faced severe difficulties in explaining the
      guidance of attention by the information processor's goals and intentions.
      Subsequent modifications, concerned with removing these difficulties, revealed
      that selection, guided by goals and intentions, is the essential behavioral
      feature and that the observed performance limitations are a result of this
      selection. So, the limited capacity theorizing was not only plagued by a virtus
      dormitiva explanation, it also suffered from the methodology of bad focus.

PMID- 9245465
TI  - Limited Capacity of Any Realizable Perceptual System Is a Sufficient Reason for
      Attentive Behavior

PMID- 9245466
TI  - Eye Movements and Attention

PMID- 9245467
TI  - NOTE
AB  - The relations between automatic processing and (the absence of) consciousness are
      discussed in this paper. It is argued that automatic processing should not be
      identified with the absence of consciousness. The organism has access to
      representations resulting from automatic processing, but these representations,
      in contrast to the representations resulting from nonautomatic processing, are
      not propositional. Therefore monitoring of the process, the defining feature of
      nonautomatic processing, is not possible.

PMID- 9245468
TI  - Bootstrapping Word Boundaries: A Bottom-up Corpus-Based Approach to Speech
      Segmentation
AB  - Speech is continuous, and isolating meaningful chunks for lexical access is a
      nontrivial problem. In this paper we use neural network models and more
      conventional statistics to study the use of sequential phonological probabilities
      in the segmentation of an idealized phonological transcription of the London-Lund
      Corpus; these speech data are representative of genuine conversational English.
      We demonstrate, first, that the distribution of phonetic segments in English is
      an important cue to segmentation, and, second, that the distributional
      information is such that it might allow the infant, beginning with only a
      sensitivity to the statistics of subsegmental primitives, to bootstrap into a
      series of increasingly sophisticated segmentation competences, ending with an
      adult competence. We discuss the relation between the behavior of the models and
      existing psycholinguistic studies of speech segmentation. In particular, we
      confirm the utility of the Metrical Segmentation Strategy (Cutler & Norris, 1988)
      and demonstrate a route by which this utility might be recognized by the infant,
      without requiring the prior specification of categories like "syllable" or
      "strong syllable."

PMID- 9245469
TI  - Transfer and Complexity in Artificial Grammar Learning
AB  - Implicit and explicit learning are sensitive to various degrees of complexity and
      abstractness, ranging from knowledge of first-order dependencies and specific
      surface structure to second-order dependencies and transfer. Three experiments
      addressed whether implicit learning is sensitive to this entire range of
      information or whether explicit knowledge becomes an important factor in cases of
      more complex learning. Experiment 1 used recognition and prediction to assess
      deliberate access to knowledge of letter patterns in an artificial grammar
      learning paradigm. Experiment 2 manipulated stimulus presentation and response in
      a sequence-based grammar learning paradigm. Learning can occur without awareness
      in cases of lesser complexity (such as learning first-order dependencies).
      However, more complex learning, such as that involved in learning second-order
      dependencies or in transfer to stimuli with the same underlying syntax but new
      surface features is linked to explicit knowledge. In contrast to Experiments 1
      and 2 which assessed deliberate access to knowledge of the acquisition stimuli,
      Experiment 3 assessed deliberate access to knowledge of the transfer stimuli.
      Knowledge of initial trigrams in the transfer stimuli appears to play an
      important role in transfer. These findings are evaluated in terms of postulated
      implicit learning mechanisms.

PMID- 9245470
TI  - Configural processing in memory retrieval: multiple cues and ensemble
      representations.
AB  - When retrieving information from memory, a number of contextual cues may interact
      to determine which ideas will be easily accessible. Even the simplest case in
      which joint cue action obtains (two cues) is very revealing of the principles of
      memory access and representation of compounds. Mechanisms by which dual cues
      interact to constrain retrieval from episodic memory are considered. A holistic
      mechanism of cue integration is contrasted with two nonholistic mechanisms: a
      multiplicative or intersection mechanism and an independent-contributions
      mechanism. Holistic- and intersection-cuing mechanisms are consistent with
      different variants of compound cue models of priming. The independent cuing
      mechanism is consistent with spreading activation models of priming. Data from
      four experiments which examined dual-cued recognition of items from (newly
      learned) triples demonstrated strongly configural, holistic, action of dual cues.
      The two cues and test item must form an encoded compound to yield cuing
      advantages. Two independent cues to the test item are ineffective if the two cues
      and test were not learned together as a triple; one valid and one invalid cue are
      also ineffective. This is so despite the availability of pairwise information for
      each cue-test relation, and despite the fact that these cues are effective when
      operating alone. A compound cue model which predicts precisely this surprising
      pattern of priming is developed. The compound cue model also predicts previously
      obtained configural priming of associative judgments, as well as the bias priming
      generally observed in item recognition and similar paradigms.

PMID- 9245471
TI  - Decision and Response in Dual-Task Interference
AB  - Experiments with two stimuli (S1 and S2) and two responses suggest the existence
      of a stage of processing that cannot be shared between two concurrent tasks.
      Widespread support has been found for the hypothesis that response selection for
      Task2 is postponed when the S1 to S2 stimulus onset asynchrony (SOA) is short
      (Pashler, 1994a). At short SOAs, manipulations which impact Task2 processing
      prior to response selection (e.g., degradation of stimulus quality) have little
      effect on Task2 response times (RTs). On the other hand, manipulations which are
      thought to impact response selection or execution (e.g., Stroop interference)
      always impact Task2 RTs. There is, however, one particularly compelling
      demonstration that appears to be inconsistent with the response selection
      bottleneck hypothesis: Karlin and Kestenbaum (1968) report that the RT difference
      between detection (i.e., 1-choice) and 2-choice discrimination dramatically
      decreases with decreasing SOA. Given that the primary difference between
      detection and discrimination is believed to be at response selection, their
      result may indicate a processing bottleneck at response execution (Keele, 1973).
      We fail to replicate the Karlin and Kestenbaum result in two substantive
      replications of Karlin and Kestenbaum's tasks and procedures. In the single
      experiment in which Karlin and Kestenbaum's result is replicated, a simple
      response execution bottleneck account is ruled out by the stability of the
      difference between 2-choice and 3-choice discrimination times across SOA. Two
      additional experiments demonstrate that response preparation and task strategy do
      not substantially contribute to the attenuation of response selection-level
      effects with decreasing SOA.

PMID- 9245472
TI  - Capacity limitations of a classic M-power measure: a modified dual-task approach.
AB  - A modified dual-task approach was employed with 7- to 9-year-olds in an effort to
      determine whether one of the classic M-power measures, the digit placement task,
      is indeed capacity-limited. To this end, a computerized version of a three-item
      digit placement task was administered in addition to three other computerized
      tasks: a four-item digit placement task, simple reaction time (RT) to a tone
      presented alone, and reaction time to a tone occurring during the performance of
      another three-item digit placement task. Careful examination of the data revealed
      that several critical assumptions concerning the use of the dual-task procedure
      were successfully met. This permitted a test of the extent to which dual-task RTs
      were predictive of accuracy in the harder, four-item digit placement task. Not
      only was this relationship significant, but after partialling out other possible
      sources of variance, a significant correlation remained, indicating that the
      digit placement task is indeed capacity-limited.

PMID- 9245474
TI  - Cognitive bias in spider fear and control children: assessment of emotional
      interference by a card format and a single-trial format of the stroop task.
AB  - The aim of the study was to clarify whether fear in children is related to a
      distorted cognitive processing of fear-related information. In anxious children,
      only a few studies of this bias were performed which yielded inconsistent
      results. Martin, Horder, and Jones (1992. Cognition and Emotion, 6(6), 479-486)
      found a bias for spider words in spider-fear children, using a card format of the
      Stroop task. However, by using a single-trial format of the Stroop task, we
      previously found that both anxious and control children favored the processing of
      threatening information (Kindt, Brosschot, & Everaerd, 1997. Journal of
      Experimental Child Psychology, 64, 79-97). In the present study, we administered
      both a card format and a single-trial format of the Stroop task to spider-fear
      and control children. In line with our previous results, a bias for spider words
      was observed in spider fear but also in control children, regardless of the
      format used. Furthermore, the processing biases assessed by the two formats did
      not correlate, which suggests that they measure different mechanisms and/or that
      one or both mechanisms are unstable. It is speculated that certain cognitive
      developmental deficits in regulating emotions may be a vulnerability factor in
      the etiology of anxiety disorders.

PMID- 9245473
TI  - A use of self-instruction to extend the generalization of a self-instructed in
      common discrimination.
AB  - Three typically developing preschool children were presented with an in-common
      sorting problem involving colored and marked shapes; the task was to see what two
      pictures had in common and to sort a deck of pictures according to that feature.
      The children failed to sort accurately. They were then taught to name the common
      features of any pair and to answer the question, "What are you looking for?"
      before sorting, to produce the form of a self-instruction (e.g., "I'm looking for
      blue triangles"). They still failed to sort accurately until they were taught to
      link their sorting to that potentially self-instructive answer. They then showed
      perfect accuracy in sorting and occasional spontaneous overt self-instructions,
      when told only, "Put here what these pictures have in common," across ever
      changing pairs (much like the children of prior reports). The present report asks
      whether that finally correct performance would generalize to new stimuli.
      Accordingly, the children were probed with steadily changing sample pairs of
      three new stimulus sets-recombinations of the colored, marked shapes used in
      training; letters; and pictures. One child showed near-perfect generalization to
      all three of these new sets (like many children in prior reports). But the other
      two children showed near-perfect generalization to only two of the sets and not
      to the third Set-letters. Merely reintroducing the content-free question, "What
      are you looking for?" and acknowledging correct answers to it (i.e., self
      instructions about letters) yielded largely accurate sorting of letter problems;
      this way of remediating failures of generalization had not been studied before.
      In general, sorting problems with two elements in common proved more difficult
      than those with one element in common; this difference diminished in the child
      told to self-instruct about letters after that self-instruction.

PMID- 9245475
TI  - A change in viewpoint promotes use of height-in-picture as a depth cue in 5- to 7
      year-olds' drawings of a simple depth relationship.
AB  - Height-in-picture emerges between 6 and 7 years of age in children's drawings as
      the first indication of portrayal of depth relationships, but can be promoted
      earlier by the use of a number of experimental manipulations. The present studies
      investigate whether changing, and hence drawing attention to, the child's
      viewpoint promotes use of height-in-picture. In the first study, 5/6- and 6/7
      year-old children were asked to draw two blocks, arranged in depth. Following
      this, the child-array relationship was altered, either by moving the child
      through 90 degrees or by rotating the array through 90 degrees. Children then
      drew again what was now a left-right arrangement, whereupon the transformation
      was reversed and they made a final drawing. Only when children moved to a new
      standpoint was there a significant increase in vertical portrayal between first
      and third drawings. It was not simply the movement of the child that prompted use
      of height-in-picture because there was no such effect in conditions in which the
      child was moved but made an unrelated drawing from the new position. These
      results indicate that making viewpoint salient by asking for a drawing from a new
      position prompts young children to portray a simple depth relationship.

PMID- 9245476
TI  - Are speech perception deficits associated with developmental dyslexia?
AB  - Phonological awareness and phoneme identification tasks were administered to
      dyslexic children and both chronological age (CA) and reading-level (RL)
      comparison groups. Dyslexic children showed less sharply defined categorical
      perception of a bath-path continuum varying voice onset time when compared to the
      CA but not the RL group. The dyslexic children were divided into two subgroups
      based on phoneme awareness. Dyslexics with low phonemic awareness made poorer /b/
      /p/ distinctions than both CA and RL groups, but dyslexics with normal phonemic
      awareness did not. Examination of individual profiles revealed that the majority
      of subjects in each group exhibited normal categorical perception. However, 7 of
      25 dyslexics had abnormal identification functions, compared to 1 subject in the
      CA group and 3 in the RL group. The results suggest that some dyslexic children
      have a perceptual deficit that may interfere with processing of phonological
      information. Speech perception difficulties may also be partially related to
      reading experience.

PMID- 9245477
TI  - The emergence of perceptual category representations in young infants: a
      connectionist analysis.
AB  - There has been recent interest in the idea that principles governing learning in
      connectionist networks can form the basis for an alternative understanding of
      developmental processes (Elman, Bates, Karmiloff-Smith, Johnson, Parisi, &
      Plunkett, 1996). The present paper can be viewed as a case example of the
      usefulness (and limitations) of connectionist modeling for the study of infant
      cognition. Specifically, the paper reports on a series of connectionist models
      designed to analyze the factors responsible for the emergence of global-level and
      basic-level category representations in young infants. The models (1) simulated
      the formation of global-level and basic-level representations, (2) revealed a
      global-to-basic order of category emergence, (3) uncovered the formation of two
      distinct global-level representations-an initial "self-organizing" perceptual
      global level and a subsequently "trained" arbitrary (i.e., nonperceptual) global
      level, and (4) displayed a gradual transition from perceptual global-level to
      perceptual basic-level representation with increasing exposure to training
      stimuli. Hypotheses for empirical investigations of category development in
      infants that follow from the modeling efforts are discussed.

PMID- 9245478
TI  - Development of size modification of human figure drawings in spatial axes systems
      of varying complexity.
AB  - In the present study, intraindividual development of the ability to modify the
      size of the human figure drawing was investigated. In a longitudinal data set
      with repeated measurement at ages 7, 9, and 12 it was shown that size was reduced
      between 7 and 9 years. Three factors were found to be responsible for size
      variation of the human figure drawing: The larger the figure initially, the more
      complex the level of the spatial axes system and the more persons in the picture,
      the greater size reduction.

PMID- 9245479
TI  - Cloning and expression of human endothelial-monocyte-activating polypeptide 2
      (EMAP-2) and identification of its putative precursor.
AB  - Endothelial-monocyte-activating polypeptide 2 (EMAP-2) modulates a range of
      properties of endothelial cells, monocytes and neutrophils in vitro, and induces
      an acute inflammatory reaction and tumour regression in vivo. We generated the
      full-length human cDNA sequences of EMAP-2 and its putative precursor pro-EMAP-2
      as PCR products. These were cloned into the pCR3 vector and subcloned into pGEX
      2T for expression as fusion products with glutathione-S-transferase (GST).
      Recombinant EMAP-2 (rEMAP-2) was isolated by thrombin cleavage of the fusion
      protein, followed by affinity chromatography. rEMAP-2 retained biological
      activity, which was blocked by polyclonal antibodies raised against GST-EMAP-2.
      By Western blotting, a 34-kDa product corresponding to the predicted precursor
      proEMAP-2 was detected in lysates of the U937 monocytic cell line, while
      supernatants contained higher levels of the mature 22-kDa molecule.

PMID- 9245480
TI  - LERK-7: a ligand of the Eph-related kinases is developmentally regulated in the
      brain.
AB  - The eph family is the largest subfamily of receptor tyrosine kinases (RTKs).
      Members of this subfamily display specific expression in the developing and adult
      brain. Recently, cDNAs encoding membrane bound ligands for these receptors have
      been identified which we have termed LERKs (ligand for eph-related kinases). We
      report here the isolation of LERK-7 from a human fetal brain cDNA library. LERK-7
      encodes a protein of 228 amino acids and is anchored to the membrane by glycosyl
      phosphatidylinositol (GPI) linkage. When transfected into CV1/EBNA cells, LERK-7
      binds soluble forms of both hek and elk. In addition, a soluble form of LERK-7
      will induce phosphorylation of eck expressed in a human duodenum adenocarcinoma
      cell line. LERK-7 expressed multiple transcripts (7.5-kb, 6.0-kb, and 3.5-kb)
      with the highest levels in human adult brain, heart, spleen, and ovary and human
      fetal brain, lung, and kidney. Similar to the other ligands in this family, LERK
      7 is developmentally regulated in the brain. LERK-7 is identical to the recently
      described AL-1.

PMID- 9245481
TI  - Structural immuno-analysis of human and porcine interferon gamma: identification
      of shared antigenic domain.
AB  - We examined the antigenic resemblance between human (h) and porcine (p)
      interferon (IFN)-gamma by binding (ELISA) and neutralization assays. The murine
      polyclonal antisera and sets of murine monoclonal antibodies (mAbs) raised
      against either IFN were tested in confrontation with recombinant IFNs of either
      species, and with site-specific mutants of hIFN-gamma. Several of the mAbs raised
      against pIFN-gamma cross-reacted in ELISA with hIFN-gamma. In contrast, none of
      the anti-hIFN-gamma mAbs cross-reacted. By employing site-specific mutants of
      recombinant hIFN-gamma as antigens in ELISA we succeeded in identifying the C
      terminal portion 97-111 as the antigenic site in hIFN-gamma recognized by the
      cross-reactive anti-pIFn-gamma mAbs. None of the mAbs recognizing the common
      antigenic structure had neutralizing potency, although His111 was determined by
      others as the residue important for bioactivity of hIFN-gamma. Mutations in the
      domain 97-111 had no or little influence on homospecific reactivity of anti-hIFN
      gamma mAbs, indicating that this domain, while being mouse-immunodominant in the
      case of pIFn-gamma was poorly immunogenic in the case of hIFN-gamma. The epitopes
      of three out of five anti-hIFN-gamma mAbs mapped in the N-terminal region 1-23,
      indicating immunodominance of this region in hIFN-gamma. Another mAb (D9D10),
      also directed to the N-terminus of hIFN-gamma, apparently recognized a
      conformational epitope. This antibody lacked ELISA-reactivity with the wild-type
      hIFN-gamma but strongly bound mutant protein with an engineered disulfide bridge
      Cys7-Cys69. Surprisingly, D9D10 showed high reactivity also with the wild type
      hIFN-gamma produced by baculovirus construct coding for the mature protein with
      signal sequence or with wild type protein possessing residues Cys-Tyr-Cys from
      the signal sequence.

PMID- 9245482
TI  - Constitutive and inducible expression of endothelin-1 in primary rat articular
      chondrocyte culture.
AB  - Endothelin-1 (ET-1) mRNA expression and protein production were examined in
      primary rat articular chondrocyte (AC) cultures by RT-PCR and radioimmunoassay,
      respectively. We found that serum-starved rat AC express ET-1 mRNA and produce
      the peptide constitutively. Treatment of cells with 10% FCS resulted in a marked
      increase in ET-1 levels with a peak at 48 h (5.6-fold). A similar concentration
      dependent effect was also obtained in the presence of interleukin 1beta (3.1
      fold), tumour necrosis factor alpha (3. 5-fold), lipopolysaccharide (2.7-fold),
      transforming growth factor beta1 (3.5-fold), epidermal growth factor (5.0-fold)
      and insulin-like growth factor-I (4.4-fold). In addition, ET-1 was found to
      induce, over a period of 24 h, a potent concentration-dependent stimulation of
      DNA synthesis in rat AC. These findings demonstrate for the first time the
      constitutive expression and production of ET-1 by rat AC which could be modulated
      by several cytokines and growth factors, suggesting a possible role for ET-1 in
      autocrine regulation of chondrocyte function.

PMID- 9245483
TI  - Dexamethasone prevents interleukin-1beta-mediated inhibition of rat islet insulin
      secretion without decreasing nitric oxide production.
AB  - The deleterious effects of interleukin 1 (IL-1) on insulin-producing beta-cells
      are partly mediated by the generation of the free radical nitric oxide (NO). We
      aimed to assess the effect of several steroidal hormones on IL-1beta-induced
      inhibition of rat islet insulin secretion in vitro, and their possible regulatory
      effects on NO production. Incubation of newborn rat islets for 24 h in the
      presence of 150 pg/ml IL-1beta revealed that dexamethasone dose-dependently
      attenuated the inhibitory effect of IL-1beta on insulin release in response to a
      2-h glucose challenge. Physiological and supraphysiological concentrations of
      testosterone, 17beta-estradiol, progesterone, 1,25-dihydroxyvitamin-D3 and
      vitamin D analogues (KH1060 and MC1288) were ineffective. Dexamethasone (1
      microM) increased the production of NO in IL-1beta-treated rat islets, as
      measured by the concentration of nitrite in the media. However, 1-5 microM
      dexamethasone inhibited IL-1beta-induced NO production by RIN cells.
      Dexamethasone (1 microM) did not affect the inhibitory action of the NO donor S
      nitroso penicillamine (500 microM) on rat islet insulin secretion. We conclude
      that dexamethasone partially protects against IL-1beta-induced inhibition of rat
      islet insulin secretion, an effect which is not mediated through modulation of
      the NO pathway.

PMID- 9245484
TI  - Interleukin 1beta-mediated inhibition of arginase in RINm5F cells.
AB  - Induction of nitric oxide synthase and generation of nitric oxide in pancreatic
      islet beta-cells may mediate cytokine-induced dysfunction leading to insulin
      dependent diabetes mellitus. Nitric oxide generation can be regulated by
      availability of arginine substrate which, in turn, may be affected by substrate
      utilization in competing pathways such as the arginase-catalysed formation of
      ornithine and urea. In this study we have investigated the activity of arginase
      in the rat insulinoma-derived cell line RINm5F and the effect on this of
      interleukin 1beta, the nitric oxide synthase reaction intermediate NG-hydroxy-l
      arginine and the nitric oxide-generating compounds 3-morpholinosydnonimine and S
      nitrosoglutathione. Cytosols from RINm5F cells treated with or without
      interleukin 1beta (0.1nM, 18h) were incubated (45min, 37 degrees C) with [U
      14C]arginine. Radiolabelled products ([14C]citrulline from nitric oxide synthase,
      [14C]ornithine and [14C]urea from arginase) were separated by high-performance
      liquid chromatography or ion-exchange chromatography. Interleukin 1beta increased
      citrulline production (from 0.01+/-0.002 to 0.58+/-0.03 pmol/microg cell
      protein), indicating induction of nitric oxide synthase, and significantly
      decreased production of both ornithine (from 4.60+/-0.20 to 3.40+/-0.20
      pmol/microg) and urea (0.93+/-0.05 to 0.69+/-0.04 pmol/microg) (P<0.001),
      indicating decreased activity of arginase. Arginase was significantly inhibited
      by NG-hydroxy-l-arginine (IC50=50 microM), S-nitrosoglutathione (500 microM: 69+/
      7% of control) and 3-morpholinosydnonimine (1 mM: 57+/-7% of control) (P<0.05).
      We conclude that during cytokine-directed beta-cell assault nitric oxide synthase
      catalysed production of NG-hydroxy-l-arginine and nitric oxide may inhibit
      arginase thereby increasing the availability of arginine for nitric oxide
      production.

PMID- 9245485
TI  - Interleukin-1beta-induced expression of protein kinase C (PKC)-delta and epsilon
      in NIH 3T3 cells.
AB  - NIH 3T3 cells express the alpha, delta, epsilon and zeta isoenzymes of protein
      kinase C(PKC). Following stimulation of cells (24 h) with the pro-inflammatory
      cytokine, interleukin 1beta (IL-1beta), we observed, by Western blotting, a dose
      dependent effect on the levels of PKC-epsilon and delta, but not on alpha or
      zeta. Moreover, time course analysis revealed that the isoenzymes, PKC-delta and
      epsilon were induced by IL-1beta after 7 h. Again, no change in PKC-alpha or zeta
      levels after IL-1beta treatment were detected. Incubation with selective PKC
      inhibitor peptides blocked the PKC-alpha, delta, epsilon and zeta antibodies
      binding to their respective isoenzyme bands. We also observed that the addition
      of the tumour-promoting phorbol ester, Phorbol 12-myristate 13-acetate (PMA),
      downregulated PKC-alpha, delta and epsilon by 7 h in NIH 3T3 cells. PMA did not
      affect constitutively produced PKC-zeta protein levels even after 24-h treatment.
      In summary, these results demonstrate that IL-1beta induces protein synthesis of
      the Ca2+-independent PKC-delta and epsilon isoforms in NIH 3T3 cells. The
      differences observed here between PKC isoenzymes in response to IL-1beta suggest
      that each isoenzyme may have a unique role in the signal transduction pathways of
      IL-1beta and that such isoenzyme may have a unique role in the signal
      transduction pathways of IL-1beta and that such selective expression may
      influence the action of agents which require PKC for signal transduction acting
      in concert with IL-1.

PMID- 9245486
TI  - The inhibitory effect of rolipram on TNF-alpha production in mouse blood ex vivo
      is dependent upon the release of corticosterone and adrenaline.
AB  - Intraperitoneal administration of the phosphodiesterase type 4 (PDE4) inhibitor
      rolipram (1-30 mg/kg) caused a dose-dependent increase in the circulating levels
      of both corticosterone and adrenaline in male Balb/c mice. These increases were
      maximal 0.5-1 h after administration of rolipram and had declined to control
      levels by 4 h. Rolipram (10 mg/kg i.p.) substantially inhibited the production of
      tumour necrosis factor alpha (TNF-alpha) ex vivo in blood from normal mice but
      was ineffective in adrenalectomized mice, suggesting that the inhibitory effect
      of rolipram is dependent on intact adrenal function. The corticosterone
      antagonist, RU 486, and the beta-adrenoceptor antagonist, propranolol, both
      partially reversed the inhibitory activity of rolipram while the combination of
      RU 486 and popranolol abrogated the effect of the rolipram to the same degree as
      adrenalectomy. These data suggest the release of both corticosterone and
      adrenaline contribute to the ability of rolipram to inhibit TNF-alpha production
      in mouse blood ex vivo.

PMID- 9245487
TI  - Receptor-mediated endocytosis of IL-8: a fluorescent microscopic evidence and
      implication of the process in ligand-induced biological response in human
      neutrophils.
AB  - Interleukin 8 (IL-8), a neurophil-activating and chemotactic cytokine, is known
      to play a key role in the pathogenesis of a large number of neutrophil-driven
      inflammatory diseases. Although the cytokine is rapidly internalized at 37
      degrees C with its receptors, there was no direct evidence for the ligand-induced
      endocytosis of the receptor or that of the interaction of receptor ligand complex
      at 37 degrees C. As a result, our understanding about the regulation of Il-8
      induced biological response is very limited. In the present study, using FITC-IL
      8 conjugate as a probe, we have demonstrated the time- and temperature-dependent
      endocytosis of IL-8 under fluorescent microscope. We have also shown that the
      bright fluorescent light on the surface of neutrophils gradually disappears and
      it becomes almost dark after 120 min of incubation. Monodansyl cadaverine (MDC,
      900 microM), however, was found to retain the fluorescent light of FITC coupled
      with Il-8 on the cells. MDC and ouabain (2.5 mM) can inhibit the ligand induced
      endocytosis by 76% and 96%, respectively, compared to control. With respect to
      control, IL-8 induced biological responses e.g. IL-8 directed migration,
      intracellular Ca2+ release and superoxide release are significantly reduced by
      77%, 94% and 76%, respectively, in presence of MDC. The study presents a direct
      visual evidence of the time and temperature-dependent receptor-mediated
      endocytosis of IL-8 which is inhibited by MDC and ouabain. This information is
      useful for understanding the ligand receptor interaction at 37 degrees C and may
      be useful for developing anti-inflammatory agents against IL-8.

PMID- 9245488
TI  - New TNF-alpha analogues: a powerful but less toxic biological tool against
      tumours.
AB  - Our approach to the modification of recombinant human tumour necrosis factor
      alpha (rhTNF-alpha) comprised changes in flexible loop regions on the surface of
      the TNF molecule. Using this approach, two different rhTNF-alpha analogues LK 801
      and LK 805 were synthesized and tested for their ability to affect the growth of
      Sa-1 tumour cells. Results obtained in vitro indicate that neither rhTNF-alpha
      nor its analogues have a direct cytotoxic effect. In vivo experiments were
      performed on subcutaneous Sa-1 tumours in A/J mice, where the antitumour effect
      and the toxic side effects of the cytokines were followed. There was no
      significant difference between growth delay of tumours in animals treated with
      native rhTNF-alpha and in animals treated with one of the analogues. On the
      contrary, the LD50 for rhTNF-alpha was 29.1 microg, for LK 801 59.3 microg, and
      for LK 805 even 66.1 microg, indicating that LK 801 and especially LK 805 were
      significantly better tolerated. The results confirm that the rhTNF-alpha molecule
      has been successfully modified resulting in two new analogues with a potent
      antitumour activity and much lower systemic toxicity. A particularly low systemic
      toxicity and a strong antitumour effect were observed after treatment with LK 805
      suggesting that this analogue merits further investigation in pre-clinical and
      clinical trials.

PMID- 9245489
TI  - Mitigating effects of interleukin 11 on consecutive courses of 5-fluorouracil
      induced ulcerative mucositis in hamsters.
AB  - Ulcerative mucositis is a painful, debilitating and dose-limiting toxicity of
      cancer chemotherapy. Current treatment is largely palliative and no adequate
      preventive treatment exists. Recently, we reported that recombinant human(rh)
      interleukin 11 (IL-11) favourably modified the course of mucositis following a
      single stomatotoxic regimen of 5-fluorouracil in hamsters. Although potentially
      beneficial, the clinically relevant issue of mucositis and myelosuppression
      during multicourse chemotherapy treatment was not addressed. The present study
      was undertaken to evaluate the effect of rhIL-11 on two consecutive courses of
      mucositis and myelosuppression in hamsters. Ulcerative mucositis was induced
      using a standardized protocol consisting of 5-fluorouracil (60 mg/kg) on days 1
      and 2 followed by superficial irritation of the buccal mucosa on day 4. Animals
      treated with 100 microg of rhIL-11 for 12 consecutive days following each regimen
      of chemotherapy experienced a reduction in the incidence, severity, and duration
      of mucositis, a reduction in weight loss, and less morbidity and mortality
      relative to control animals. Bone marrow cellularity and function was not
      adversely affected by rhIL-11 treatment. The present study is consistent with the
      potential use of rhIL-11 treating patients at risk of developing ulcerative
      mucositis while undergoing intensive multicourse chemotherapy treatment.

PMID- 9245490
TI  - Differential effects of transforming growth factor beta2, dexamethasone and 1,25
      dihydroxyvitamin D on human bone marrow stromal cells.
AB  - We have studied the effects of rhTGF-beta2, dexamethanosome (dex) and 1,25(OH)2D3
      on human bone marrow stromal (HBMS) cells in long-term culture. A fraction on
      HBMS expressed type I collagen (Col I) and osteopontin, and transient treatment
      (48 h) with dex increased the number of alkaline phosphatase (ALP) positive
      cells. Treatment with rhTGF-beta2 inhibited DNA synthesis and attenuated the
      stimulatory effect of dex on cell growth at 3-4 weeks of culture. 1,25(OH)2D3
      inhibited DNA synthesis at 1-4 weeks, and dex partially blocked the inhibitory
      effect of 1,25(OH)2D3 on cell growth. rhTGF-beta2 and dex increased Col I
      synthesis at 1 week of culture. Both dex and 1,25(OH)2D3 increased ALP activity
      and mRNA levels independently, and when combined they had an additive or
      synergistic effect, whereas rhTGF-beta2 antagonized the stimulatory effect of dex
      on ALP activity. In addition, dex attenuated the increased osteocalcin expression
      induced by 1,25(OH)2D3. These results show that rhTGF-beta2, dex and 1,25(OH)2D3
      have distinct effects and modulate the action of each other on human marrow
      stromal cell proliferation and differentiation at different time points during
      the culture.

PMID- 9245491
TI  - Suppression of dialysis patients' lymphocyte IL-2R expression by glucocorticoids
      and cyclosporine.
AB  - Previous studies have shown interindividual heterogeneity in the suppressive
      effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses
      of dialysis patients' peripheral blood mononuclear cells (PBMC). In addition,
      methylprednisolone (MP) was shown to be significantly more suppressive than
      prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were found
      to be more sensitive to both glucocorticoids than those from patients on
      haemodialysis (HD). In order to begin to explore the cellular mechanism(s)
      underlying these observations, the differential suppressive effects of these
      drugs on lymphocyte interleukin 2 receptor (IL-2R) expression by mitogen
      stimulated PBMC from 23 PD and 30 HD were determined. The mean+/-SD
      concentrations (ng/ml) of steroid causing 50% inhibition (IC50) of cell
      proliferation was significantly lower for PD than HD PBMC with both P (94+/-93 vs
      148+/-105, P<0.05) and MP (21+/-25 vs 35+/-31, P<0.05). MP was significantly
      (P<0.001) more suppressive than P of IL-2R expression in both PD and HD. PD IL-2R
      expression was significantly (P<0.05) more suppressed by CsA alone and by 400
      ng/ml CsA+10(-7) MP than was HD IL-2R expression. CsA+10(-7) M MP was
      significantly (P<0.001) more suppressive of IL-2R expression than the other
      drugs, alone or in combination, in both groups of patients. In conclusion, these
      results support the notion that at least one mechanism underlying the
      significantly greater efficacy of MP compared to P in suppressing PBMC
      proliferation is its significantly greater suppression of lymphocyte IL-2R
      expression, either alone or in combination with CsA. Thus, use of MP following
      allograft transplantation may result in more effective immunosuppression for many
      recipients.

PMID- 9245492
TI  - Rapid detection of cerebrospinal fluid (CSF) cytokines in children by long-term
      external shunt (ES): preliminary report.

PMID- 9245494
TI  - Notch signaling in vertebrate development and disease.

PMID- 9245493
TI  - The ins and outs of notch signaling.
AB  - The Notch gene encodes a cell surface protein that regulates cell fate choices in
      vertebrates and invertebrates. Given the wide variety of cell types influenced by
      Notch, it would seem that the signal relayed through Notch activation is not an
      instructive one per se. Rather, Notch signaling is thought to influence the
      cell's ability to respond to instructive signals responsible for specific cell
      fates. Expression and functional studies of Notch support this idea; however, the
      possibility of additional functions for Notch cannot be excluded. Much of what we
      know about the Notch signaling pathway comes from studies with Drosophila Notch
      and the Caenorhabditis elegans Notch-related genes lin-12 and glp-1. With the
      isolation of multiple vertebrate Notch genes we are beginning to understand and
      define Notch signaling in vertebrates as well. A number of excellent reviews have
      been published summarizing the current status of Notch/LIN-12/GLP-1 signaling in
      Drosophila and C. elegans, as well as recent findings with the vertebrate
      counterparts. Here I review the structure of the various Notch proteins and their
      putative ligands, and discuss possible interactions between Notch, its ligands,
      and other cellular components that affect Notch signal transduction. A role for
      Notch signaling during normal development and in disease processes is discussed
      in an accompanying review by T. Gridley (1997, Mol. Cell. Neurosci. 9: 103-108).

PMID- 9245495
TI  - Axonal molecules of the immunoglobulin superfamily bearing a GPI anchor: their
      role in controlling neurite outgrowth.

PMID- 9245496
TI  - Axon-regenerating retinal ganglion cells in adult rats synthesize the cell
      adhesion molecule L1 but not TAG-1 or SC-1.
AB  - Retinal ganglion cells (RGCs) in rats regenerate axons in the presence of a PNS
      nerve graft. To determine if axon-regenerating RGCs synthesize cell
      adhesion/recognition molecules which they possessed during development, retinae
      were subjected to in situ hybridization with antisense cRNA probes of L1, TAG-1,
      and SC-1 (and GAP-43 for comparison). L1 and TAG-1 (and GAP-43) proteins on axons
      were detected with antibodies. L1, TAG-1, and SC-1 (and Gap-43) mRNAs and L1 and
      TAG-1 (and Gap-43) proteins were expressed by RGCs in embryonic, postnatal, and
      adult rats. After optic nerve lesion (ONL), the surviving RGCs between 2 and 28
      days after ONL continued to express L1. TAG-1 and SC-1 expression, however is
      lost. In grafted rats, axon-regenerating RGCs express L1 (together with GAP-43)
      but neither TAG-1 nor SC-1. Thus, axonal regeneration in grafted rats occurs in
      the presence of L1 (and GAP-43) but in the absence of TAG-1 and SC-1).

PMID- 9245497
TI  - Chick muscle expresses various ARIA isoforms: regulation during development,
      denervation, and regeneration.
AB  - Acetylcholine receptor inducing activity (ARIA) is a glycoprotein released from
      the motor neuron to stimulate the synthesis of acetylcholine receptors (AChRs) on
      the postsynaptic muscle fiber. Transcripts encoding ARIA were detected not only
      in brain but also in muscle, and immunohistochemical staining showed that muscle
      derived ARIA was restricted to the neuromuscular junctions. RT-PCR analysis
      revealed three biological active isoforms of ARIA in chick muscle, namely ARIA
      beta 1, ARIA alpha 2, and ARIA beta 2 that were classified based on their
      variation in the carboxylterminus of the EGF-like domain. The expression of these
      ARIA isoforms in muscle change during development denervation, and nerve
      regeneration. ARIA beta 1, ARIA alpha 2, and ARIA beta 2 were expressed in
      embryonic and young chick muscles, while ARIA beta 1 was the major isoform
      expressed in adult chicken. The embryonic-like expression of ARIA alpha 2 and
      ARIA beta 2 was induced after nerve injury in adult chicken. However, the
      prominent expression of ARIA beta 1 in adult-like profile was restored after
      nerve regeneration. A splicing variation in the region between Ig-like and EGF
      like domains of ARIA was also revealed; a zero-amino acid insertion (ARIASP0), a
      17-amino acid insertion (ARIASP17), or a 34-amino acid insertion (ARIASP34) were
      identified. Unlike ARIASP0, the expression of ARIASP17 and ARIASP34 was found in
      muscle and sciatic nerve only. The expression of ARIASP0, ARIASP17, and ARIASP34
      in chick muscle remained unchanged during development and after nerve injury.
      Moreover, the specific expression of these ARIA isoforms in cultured myotubes was
      not affected by drug treatments or by coculturing with neurons. Our findings
      provide strong evidence that muscle ARIA may play an important role in the
      formation of neuromuscular junctions.

PMID- 9245498
TI  - Mutational analysis of the L1 neuronal cell adhesion molecule identifies membrane
      proximal amino acids of the cytoplasmic domain that are required for cytoskeletal
      anchorage.
AB  - The preferential localization of the L1 cell adhesion molecule in the axons and
      growth cones of differentiating neurons suggests the existence of a mechanism for
      targeting or anchoring the molecule to these locations. We have used B28 glioma
      cells, which have an extremely flattened morphology, as a model system to study
      the organization of L1 on the cell structure. Transfection of L1 cDNA into B28
      cells results in expression of the L1 protein in organized linear cell surface
      arrays which are codistributed with cytoskeletal stress fibers, but not with
      microtubles or intermediate filaments. Transfection studies with L1 deletion
      mutants identify the juxtamembrane segment of the cytoplasmic domain as the
      critical entity for arrangement of L1 into ordered cell surface arrays. The
      seventh cytoplasmic amino acid of L1, lysine 1150, and to a lesser extent the
      fourth cytoplasmic amino acid, lysine 1147, appear to be critical residues for
      maintaining normal L1 anchorage and distribution.

PMID- 9245499
TI  - Caspase inhibition selectively reduces the apoptotic component of oxygen-glucose
      deprivation-induced cortical neuronal cell death.
AB  - Cultured mouse cortical neurons undergo apoptosis when exposed to staurosporine.
      The cell-permeable caspase inhibitor Z-Val-Ala-Asp fluoromethylketone (Z-VAD.FMK)
      attenuated this death, without altering overall protein synthesis. Z-VAD.FMK also
      attenuated cortical neuronal apoptosis induced by removal of serum. However, Z
      VAD.FMK did not attenuate the excitotoxic necrosis induced by 5-min exposure to
      100 microM NMDA, 24-h exposure to 100 microM kainate, or 90-min exposure to
      oxygen-glucose deprivation. We have previously shown that blockade of the
      excitotoxic component of oxygen-glucose deprivation-induced neuronal death with
      glutamate antagonists unmasks an apoptotic death. Treatment with Z-VAD.FMK, but
      not the cathepsin-B protease inhibitor Z-Phe-Ala fluoromethylketone (Z-FA.FMK),
      also attenuated this oxygen-glucose deprivation-induced neuronal apoptosis. These
      data support the idea that brain caspases mediate the apoptotic component of
      oxygen-glucose deprivation-induced neuronal death and raise the possibility that
      combining caspase inhibitors with glutamate antagonists might attenuate brain
      damage induced by hypoxic-ischemic insults in vivo.

PMID- 9245500
TI  - Polarized expression of the antidepressant-sensitive serotonin transporter in
      epinephrine-synthesizing chromaffin cells of the rat adrenal gland.
AB  - Antidepressant-sensitive serotonin (5-hydroxytryptamine, 5HT) transporters
      (SERTs) clear the amine from extracellular spaces in the CNS and periphery as a
      mechanism for transmitter inactivation and recycling. Although it is known that
      SERTs are preferentially expressed on basolateral domains in transfected
      epithelial cells, details of the transporter's membrane localization in vivo are
      lacking. 5HT and 5HT receptors have been identified in the rodent adrenal gland.
      Using SERT antagonist autoradiography, we establish the presence of
      antidepressant-sensitive transport sites in the rat adrenal medulla.
      Immunofluorescence experiments using antibodies specific for the SERT COOH and
      NH2 termini, for 5HT, or for catecholamine biosynthetic enzymes suggest that SERT
      mediates intra-cellular 5HT accumulation by epinephrine-secreting chromaffin
      cells. Using confocal microscopy, we establish that SERT expression is
      nonuniformly distributed along the plasma membrane of chromaffin cells. Notably,
      SERT immunoreactivity is largely absent from plasma membranes bordering smooth
      muscle that surrounds vascular sinusoids. Rather, SERT is highly expressed in
      membranes adjoining other chromaffin cells, consistent with a role for 5HT and
      SERT in autocrine or paracrine control of chromaffin cell physiology. SNAP-25, a
      t-SNARE protein implicated in neurotransmitter release, was found to colocalize
      with SERT. In contrast, Na,K ATPase and NCAM are uniformly distributed along the
      entire perimeter of chromaffin cell membranes. These findings underscore a role
      for 5HT and SERT in adrenal physiology, reveal unrecognized polarity of
      chromaffin cell plasma membranes, and warrant a consideration of common targeting
      mechanisms localizing amine transporters near release sites.

PMID- 9245501
TI  - The motor neuron degeneration (mnd) gene acts intrinsically in motor neurons and
      peripheral fibroblasts.
AB  - In motor neuron degeneration (mnd/mnd) mice, multiple cell types develop
      cytopathology and motor neurons degenerate prematurely. Here, to investigate
      whether the expression of mnd within affected cells is responsible, we analyzed
      the evolution of cellular pathology in aggregation chimeras containing cells of
      both mnd/mnd and +/+ genotypes. In addition, skin fibroblasts were maintained in
      vitro in the absence of other cell types and examined for their disease
      manifestation. In the chimeras, neuronal genotype was identified by expression of
      an unrelated transgene. Consistent with an intrinsic action of mnd, the genotype
      and phenotype of motor neurons correlated perfectly. In addition, abnormal
      lipopigment accumulation, signifying the disease phenotype, evolved in the
      cultured fibroblasts. We conclude that neurons and fibroblasts develop
      pathological abnormalities in response to intrinsic expression of the mnd
      mutation. Further, as cellular pathology is not attenuated in the chimeric
      environment, it is unlikely that mnd and its human counterparts, neuronal caroid
      lipofuscinoses, will be responsive to a treatment strategy involving
      transplantation of normal cells.

PMID- 9245502
TI  - Subunit interactions in the assembly of neuronal Kir3.0 inwardly rectifying K+
      channels.
AB  - Cardiac G protein-activated Kir (GIRK) channels may assemble as heterotetrameric
      polypeptides from two subunits, Kir3.1 and Kir3.4. For a functional comparison
      with native channels in the CNS we investigated all possible combinations of
      heteromeric channel formation from brain Kir3.1, Kir3.2, Kir3.3, and Kir3.4
      subunits in mRNA-injected Xenopus oocytes. Analysis of macroscopic current
      amplitudes and channel gating kinetics indicated that individual subunits or
      combinations of Kir3.2, Kir3.3, and Kir3.4 formed functional channels
      ineffectively. Each of these subunits gave rise to prominent currents with
      distinct characteristics only in the presence of Kir3.1 subunits. Functional
      expression of concatemeric constructs between Kir3.1 and Kir3.2/3.4 subunits as
      well as coimmunoprecipitations with subunit-specific antibodies confirmed
      heteromeric channel formation. Mutational swapping between subunits of a single
      pore loop residue (Kir3.1F137S; Kir3.3S114F; a phenylalanine confers slow channel
      gating in Kir3.1 subunits) revealed that Kir3.1 subunits are an important
      constituent for native heteromeric channels and dominate their functional
      properties. However, homomeric channels from Kir3.1 subunits in vivo may not
      exist due to the spatial conflict of bulky phenylalanines in the pore structure.

PMID- 9245503
TI  - Neurotrypsin, a novel multidomain serine protease expressed in the nervous
      system.
AB  - We have cloned a novel murine cDNA encoding a multidomain serine protease, termed
      neurotrypsin, which exhibits an unprecedented domain composition. The deduced
      amino acid sequence defines a mosaic protein of 761 amino acids consisting of a
      kringle domain, followed by three scavenger receptor cysteine-rich repeats, and a
      serine protease domain. Based on comparisons of the primary structure, the
      protease domain belongs to the subfamily of trypsin-like serine proteases. In
      situ hybridization revealed that the expression of neurotrypsin in the adult
      murine nervous system is confined to distinct subsets of neurons. The most
      prominent expression was found in the cerebral cortex, the hippocampus, and the
      amygdala. Le., structures engaged in the processing and storage of learned
      behaviors and memories. Together with the recently obtained evidence that
      extracellular serine proteases play a role in neural plasticity, this expression
      pattern suggests that the extracellular proteolytic action of neurotrypsin
      subserves structural reorganizations associated with learning and memory
      operations.

PMID- 9245504
TI  - Selective phosphorylation of adult tau isoforms in mature hippocampal neurons
      exposed to fibrillar A beta.
AB  - How senile plaques and neurofibrillary tangles are linked represents a major gap
      in our understanding of the pathophysiology of Alzheimer's disease. We
      characterized a hippocampal neuronal culture system in which tau undergoes
      maturation in vivo; rat neurons maintained in culture for more than 3 weeks
      replicated the splicing and phosphorylation changes that tau undergoes upon
      maturation in situ. Using this model system, we induced an Alzheimer-like
      neuritic dystrophy following the application of fibrillar beta-amyloid. The
      dystrophy consisted of focal distortions and swellings within the neurites and an
      altered phosphorylation of the adult tau isoforms. Fibrillar beta-amyloid induced
      the concomitant activation of MAP kinase and GSK3 beta. The aberrant activation
      of several signaling pathways may lead to the abnormal phosphorylation of tau and
      neuritic degeneration.

PMID- 9245505
TI  - The determination of membrane permeability coefficients of canine pancreatic
      islet cells and their application to islet cryopreservation.
AB  - Sufficient numbers of pancreatic islets for successful allotransplantation can be
      achieved by storing and then pooling islets from several donors. Optimal MHC
      matching and infectious disease screening also require long-term storage of
      islets, and cryopreservation is currently the only practical approach.
      Cryopreservation protocols may be optimized by modeling the changes in cell
      volume and the associated damage incurred during cryoprotectant addition and
      dilution and during cooling and warming. The objective of the present work was to
      determine the following biophysical parameters of canine islet cells; the
      osmotically inactive cell volume (Vb), hydraulic conductivity (Lp),
      cryoprotectant permeability coefficient (Ps), and the reflection coefficient
      sigma. A determination of these parameters allows the simulation of cell
      responses using computer models. Islets were isolated by collagenase digestion
      and Euro-Ficoll purification. After 24 h culture, islets were dissociated into
      single cells using trypsin and 2 mM EGTA. The kinetic change in cell volume as a
      function of time after exposure to 2 M dimethyl sulfoxide (Me2SO) was measured
      using an electronic particle counter at 22, 5, and -3 degrees C. At -11 degrees
      C, cells were preloaded with 1 M Me2SO and exposed to 4 M Me2SO to prevent the
      formation of ice in the working solution. Kedem-Katchalsky theory was used to
      describe the cell volume change kinetics, and a three-parameter curve fitting was
      performed using the Marquardt-Levenberg method to determine Lp, Ps, and sigma
      values. The Lp was determined to be 0.19 +/- 0.05, 0.037 +/- 0.005, 0.020 +/-
      0.003, and 0.013 +/- 0.005 micron.min-1.atm-1 (mean +/- SD) at 22, 5, -3, and -11
      degrees C, respectively. The Ps values were 1.05 +/- 0.50, 0.15 +/- 0.04, 0.096
      +/- 0.028, and 0.067 +/- 0.029 x 10(-3) cm.min-1 at 22, 5, -3, and -11 degrees C,
      respectively. The sigma values were 0.81 +/- 0.16, 0.91 +/- 0.09, 0.80 +/- 0.21,
      and 0.98 +/- 0.04 at 22, 5, -3, and -11 degrees C, respectively. The temperature
      dependence or activation energy of Lp and Ps was calculated, using the Arrhenius
      equation, to be 12.7 and 13.5 kcal.mol-1, respectively. These permeability
      parameters were used to calculate cell water loss and the likelihood of lethal
      intracellular freezing during cooling, as well as both water flux and solute
      concentration gradients across the cell membrane during warming.

PMID- 9245506
TI  - Energy metabolism in liver of anoxia-tolerant turtle species (Pseudemys scripta):
      a model for studying hepatic tolerance to cold hypoxia.
AB  - We have studied biochemical markers of energy metabolism and glycolysis by enzyme
      analyses and 1H NMR spectroscopy in livers of the freshwater turtle, Pseudemys
      scripta, after vascular flush and cold storage. Values for hepatic ATP content
      and energy charge remained unchanged for 24 h and showed only small declines
      between 24 and 48 h of cold hypoxia. Lactate and glucose levels increased over
      the 48-h period, demonstrating, respectively, progressive glycolysis and
      glycogenolysis. These observations are in contrast to those made in mammalian
      liver, where ATP levels fall precipitously during the first few hours of cold
      hypoxia and glycolysis is inhibited. Additional changes suggested by 1H NMR
      spectroscopy may indicate a role for other metabolic pathways. Isolated organs of
      species such as Pseudemys may be useful models for studying the biochemical basis
      of resistance to cold hypoxic damage.

PMID- 9245508
TI  - Regionalized transcriptional domains of myosin light chain 3f transgenes in the
      embryonic mouse heart: morphogenetic implications.
AB  - Within the embryonic heart, five segments can be distinguished: two fast
      conducting atrial and ventricular compartments flanked by slow-conducting
      segments, the inflow tract, the atrioventricular canal, and the outflow tract.
      These compartments assume morphological identity as a result of looping of the
      linear heart tube. Subsequently, the formation of interatrial, interventricular,
      and outflow tract septa generates a four-chambered heart. The lack of markers
      that distinguish right and left compartments within the heart has prevented a
      precise understanding of these processes. Transgenic mice carrying an nlacZ
      reporter gene under transcriptional control of regulatory sequences from the
      MLC1F/3F gene provide specific markers to investigate such regionalization. Our
      results show that transgene expression is restricted to distinct regions of the
      myocardium: beta-galactosidase activity in 3F-nlacZ-2E mice is confined
      predominantly to the embryonic right atrium, atrioventricular canal, and left
      ventricle, whereas, in 3F-nlacZ-9 mice, the transgene is expressed in both atrial
      and ventricular segments (right/left) and in the atrioventricular canal, but not
      in the inflow and outflow tracts. These lines of mice illustrate that distinct
      embryonic cardiac regions have different transcriptional specificities and
      provide early markers of myocardial subdivisions. Regional differences in
      transgene expression are not detected in the linear heart tube but become
      apparent as the heart begins to loop. Subsequent regionalization of transgene
      expression provides new insights into later morphogenetic events, including the
      development of the atrioventricular canal and the fate of the outflow tract.

PMID- 9245509
TI  - Neural crest potential for tooth development in a urodele amphibian:
      developmental and evolutionary significance.
AB  - Tooth development in urodele amphibians occurs from a restricted region of
      anterior cranial neural crest. An in vitro culture system was used to test the
      odontogenic potential of more caudal regions of neural crest, including an
      "intermediate region" of neural folds which has never previously been tested for
      either fate or potential. Explants of different axial levels of neural crest with
      stomodaeal ectoderm and endoderm demonstrated that odontogenic potential extends
      not only further caudally than the axial level fated to produce teeth, but also
      beyond that with potential to produce cartilage. Our results show that
      chondrogenic potential is found only within the most rostral portion of the
      intermediate region, but that odontogenic potential extends to its most caudal
      limit. This separation of skeletogenic cell lineages in the neural crest
      necessitates a reevaluation of the designations of "cranial" and "trunk" and a
      reconsideration of the evolutionary implications of developmentally distinct
      crest-derived mesenchyme populations. The proposal that odontogenic potential
      extends into the trunk neural crest may be explained as conserved from a
      phylogenetically older, more extensive skeletogenic ability which produced the
      exoskeleton of more basal vertebrates.

PMID- 9245507
TI  - Temporal and spatial control of murine GATA-3 transcription by promoter-proximal
      regulatory elements.
AB  - GATA-3 is expressed in a temporally dynamic manner and fulfills vital functions
      during vertebrate fetal development. Homozygous mGATA-3 mutant embryos die at
      midgestation, thus complicating the analysis of its contribution to the
      development of specific cell fates in the many tissues where it is expressed
      during embryogenesis. We show here that the elements controlling GATA-3
      regulation can be precisely refined, using transgenic mice, to discrete cis
      acting domains: within 6 kb surrounding the transcriptional initiation site,
      separate sequences were found to control the expression of mGATA-3 in early
      muscle masses, in a subset of PNS neurons, in the genital tubercle, and in the
      branchial arches. The branchial arch regulatory element is particularly robust
      and was refined to a discrete enhancer sequence lying between nt -2832 and -2462
      from the transcription initiation site. The enhancer contains potential binding
      sites for many well-characterized transcription factors, suggesting that mGATA-3
      transcriptional activity may be regulated by these proteins (or related family
      members) in the mesenchyme of the arches that contribute to formation of the jaw.
      These studies show that discrete regulatory elements required for the elaboration
      of complex developmental programs can be individually localized, suggesting that
      the developmentally transient expression of individual transcription factors
      collaboratively contributes to the temporal and spatial pattern of cellular
      differentiation leading to the formation of adult anatomy.

PMID- 9245510
TI  - Rhodopsin replacement rescues photoreceptor structure during a critical
      developmental window.
AB  - Rhodopsin is essential for normal photoreceptor development in Drosophila
      (O'Tousa et al., 1989; Leonard et al., 1992; Kumar and Ready, 1995) and in mice
      (Humphries et al., 1997). Here we report studies in which a rhodopsin transgene
      is expressed at restricted stages during the development of Drosophila
      photoreceptors otherwise lacking rhodopsin. Substantial rescue of normal
      photoreceptor structure and physiology is effected by rhodopsin expression during
      the time of the normal onset of rhodopsin synthesis. Expression shortly before or
      after this critical period does not rescue these deficits. There is a critical
      developmental period in which rhodopsin plays its key role in photoreceptor
      morphogenesis.

PMID- 9245511
TI  - Glial-restricted precursors are derived from multipotent neuroepithelial stem
      cells.
AB  - Neuroepithelial cells in the developing ventricular zone differentiate into
      neurons, astrocytes, and oligodendrocytes. It is not known, however, whether this
      differentiation occurs in a single step or is a pathway utilizing intermediate
      more restricted precursor cells. To characterize the generation of glial cells
      from multipotent stem cells we have cultured neuroepithelial (NEP) cells from
      E10.5 rat embryos. Cultured NEP cells do not express any glial differentiation
      markers when grown on fibronectin/laminin under nondifferentiation conditions.
      NEP cells, however, differentiate into A2B5 immunoreactive cells which can
      subsequently give rise to oligodendrocytes and astrocytes. Clonal analysis of NEP
      cells demonstrates that the A2B5 immunoreactive cells arise in clones that
      contain neurons and astrocytes, indicating that A2B5(+) cells arise from
      multipotent NEP precursor cells. A2B5(+) cells, maintained as undifferentiated
      cells over multiple passages, can subsequently give rise to both oligodendrocytes
      and astrocytes. A2B5(+) cells, however, do not generate neurons. Thus A2B5(+)
      cells represent a restricted progenitor cell population that differentiates from
      a multipotent NEP cell. Based on our results we propose that differentiation of
      the multipotential NEP cells to terminally differentiated glial cells occurs via
      intermediate restricted precursors.

PMID- 9245512
TI  - Induction of endocardial cushion tissue in the avian heart is regulated, in part,
      by TGFbeta-3-mediated autocrine signaling.
AB  - Valvuloseptal morphogenesis of the primitive heart tube into a four-chambered
      organ requires the formation of endocardial cushion tissue. The latter is the
      outcome of an inductive interaction in which endocardial (endothelial) cells are
      induced to transform into mesenchyme by paracrine signals secreted by the
      adjacent myocardium. In this study, we propose that transforming
      endothelial/mesenchymal cells themselves secrete a factor-TGFbeta-3-that
      functions in an autocrine mode to promote/sustain mesenchyme formation and
      possibly in a paracrine manner to amplify the original (myocardial) inductive
      event. Cushion mesenchyme-conditioned medium, previously demonstrated to be an
      endogenous source of autocrine, migration-promoting factors, was found in the
      present study to contain TGFbeta-3, as detected by immunoblot analysis.
      Immunoneutralization of TGFbeta-3 in preparations of cushion mesenchyme
      conditioned medium resulted in a failure of treated target endocardial cells to
      migrate as mesenchyme, whereas inclusion of a control antibody did not inhibit
      the migration-promoting activity of the conditioned medium. Similar to treatment
      with the conditioned medium, direct addition of TGFbeta-3 to target endocardial
      cells also elicited invasive migration but only in cultures which had been
      activated in vivo by inductive interaction with the myocardium prior to
      treatment. Selective inhibition of TGFbeta-3-mediated autocrine signaling in
      continuous cocultures of endocardium plus myocardium resulted in endocardial
      cells which did not migrate, even though they had expressed early markers
      associated with endocardial cell activation (e.g., alpha-smooth muscle actin,
      ES/130, and TGFbeta-3). Collectively, these results suggest that (i) two
      signaling pathways, myocardial and endocardial, are required to start and
      complete epithelial-mesenchymal transformation in cushion-forming regions of the
      heart and (ii) the endocardial pathway signals through iteration of TGFbeta-3 and
      is not functionally redundant to the myocardial pathway.

PMID- 9245513
TI  - The removal of the sperm perinuclear theca and its association with the bovine
      oocyte surface during fertilization.
AB  - The perinuclear theca (PT) is a unique cytoskeletal structure whose anterior part
      is intercalated between the inner acrosomal membrane and the nuclear envelope of
      the mammalian sperm head and is important for spermiogenesis and stabilization of
      sperm structures (Oko and Maravei, Biol. Reprod. 50, 1000-1014, 1994; Oko and
      Maravei, Microsc. Res. Tech. 32, 520-532, 1995). Using immunofluorescence
      labeling of inseminated bovine oocytes and serial sectioning-ultrastructural
      analysis, we demonstrate that the PT is removed from the sperm nucleus following
      the loss of the sperm plasma membrane and the interaction of oocyte cortex with
      the PT. These events precede the development of the male pronucleus. The removal
      of the PT involves the elongated oocyte microvilli, rich in actin microfilaments,
      since it can be blocked by the microfilament-disrupting drug cytochalasin B.
      Reduction of disulfide bonds, which is a major factor supporting the disassembly
      of the sperm nucleus and accessory structures during mammalian fertilization,
      seems to exert little effect on the PT in vitro, as evidenced by the treatment of
      isolated bull sperm with the disulfide bond-reducing agent dithiothreitol. In
      vivo, intact bull sperm microinjected into mature oocytes do not undergo
      disassembly of the PT. Consequently, the decondensation of the sperm nucleus does
      not occur. These data suggest that the binding of the PT to the oocyte
      microvillar region and its removal from the sperm nucleus constitute an early
      step in mammalian fertilization, which is required for the conversion of the
      sperm nucleus into a male pronucleus.

PMID- 9245514
TI  - Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic
      tissues and male germ cells.
AB  - A novel paired-like homeobox gene, designated Esx1, was isolated in a screen for
      homeobox genes that regulate mouse embryogenesis. Analysis of a mouse
      interspecific backcross panel demonstrated that Esx1 mapped to the distal arm of
      the X chromosome. During embryogenesis, Esx1 expression was restricted to
      extraembryonic tissues, including the endoderm of the visceral yolk sac, the
      ectoderm of the chorion, and subsequently the labyrinthine trophoblast of the
      chorioallantoic placenta. In adult tissues, Esx1 expression was detected only in
      testes. However, Esx1 transcripts were not detected in the testes of sterile W/Wv
      mice, suggesting that Esx1 expression is restricted to male germ cells. In situ
      hybridization experiments of testes indicated that Esx1 transcripts were most
      abundant in pre- and postmeiotic germ cells. Hybridization experiments suggested
      that Esx1 was conserved among vertebrates, including amphibians, birds, and
      mammals. During mouse development, the paternally derived X chromosome is
      preferentially inactivated in extraembryonic tissues of XX embryos, including the
      trophoblast, visceral endoderm, and parietal endoderm. In addition, the X
      chromosome is transiently inactivated during the meiotic stages of
      spermatogenesis. Thus, the identification of Esx1 provides a molecular entry
      point into a genetic pathway to understand X chromosome-regulated fetal-maternal
      interactions and male germ cell development.

PMID- 9245515
TI  - VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the
      differentiated avian chorioallantoic membrane.
AB  - The lymphangiogenic potency of endothelial growth factors has not been studied to
      date. This is partially due to the lack of in vivo lymphangiogenesis assays. We
      have studied the lymphatics of differentiated avian chorioallantoic membrane
      (CAM) using microinjection of Mercox resin, semi- and ultrathin sectioning,
      immunohistochemical detection of fibronectin and alpha-smooth muscle actin, and
      in situ hybridization with VEGFR-2 and VEGFR-3 probes. CAM is drained by
      lymphatic vessels which are arranged in a regular pattern. Arterioles and
      arteries are accompanied by a pair of interconnected lymphatics and form a plexus
      around bigger arteries. Veins are also associated with lymphatics, particularly
      larger veins, which are surrounded by a lymphatic plexus. The lymphatics are
      characterized by an extremely thin endothelial lining, pores, and the absence of
      a basal lamina. Patches of the extracellular matrix can be stained with an
      antibody against fibronectin. Lymphatic endothelial cells of differentiated CAM
      show ultrastructural features of this cell type. CAM lymphatics do not possess
      mediae. In contrast, the lymphatic trunks of the umbilical stalk are invested by
      a single but discontinuous layer of smooth muscle cells. CAM lymphatics express
      VEGFR-2 and VEGFR-3. Both the regular pattern and the typical structure of these
      lymphatics suggest that CAM is a suitable site to study the in vivo effects of
      potential lymphangiogenic factors. We have studied the effects of VEGF homo- and
      heterodimers, VEGF/PlGF heterodimers, and PlGF and VEGF-C homodimers on Day 13
      CAM. All the growth factors containing at least one VEGF chain are angiogenic but
      do not induce lymphangiogenesis. PlGF-1 and PlGF-2 are neither angiogenic nor
      lymphangiogenic. VEGF-C is the first lymphangiogenic factor and seems to be
      highly chemoattractive for lymphatic endothelial cells. It induces proliferation
      of lymphatic endothelial cells and development of new lymphatic sinuses which are
      directed immediately beneath the chorionic epithelium. Our studies show that VEGF
      and VEGF-C are specific angiogenic and lymphangiogenic growth factors,
      respectively.

PMID- 9245516
TI  - Reorganization of the cortical actin cytoskeleton during maturation division in
      the Tubifex egg: possible involvement of protein kinase C.
AB  - Tubifex eggs undergo a drastic reorganization of the cortical actin cytoskeleton
      during metaphase of the second meiosis. At the end of the first meiosis, the egg
      cortex displays only scattered actin filaments and tiny dots of F-actin; during
      the following 90 min, cortical F-actin gradually increases in amount, becomes
      organized into foci that are interlinked by actin bundles, and generates a
      geodesic dome-like organization. In this study, we have characterized this
      reorganization of the cortical actin cytoskeleton. In living eggs injected with
      rhodamine-phalloidin at the beginning of the second meiosis, cortical actin
      assembly (i.e., formation of actin foci and bundles) proceeds normally, but
      labeled F-actin is not found to be included significantly in the formed cortical
      actin network, suggesting that the increase in cortical F-actin is not simply
      ascribable to the recruitment of preexisting actin filaments. Cortical actin
      assembly can be induced precociously not only by calcium ionophore A23187 but
      also by a phorbol ester PMA, an agonist of protein kinase C (PKC). Conversely,
      the formation of actin foci and bundles is inhibited by PKC antagonists, although
      cortical F-actin increases to some extent in the presence of these inhibitors.
      Similar inhibition of the cortical reorganization is elicited in eggs whose
      intracellular free calcium level ([Ca2+]i) has been clamped low by microinjection
      of a calcium chelator BAPTA. The treatment of BAPTA-injected eggs with PMA
      results in the formation of actin foci and bundles. An experiment with eggs
      injected with fluo-3 shows that [Ca2+]i increases during metaphase of the second
      meiosis. These results suggest that the reorganization of cortical actin during
      metaphase of the second meiosis requires activation of PKC, which depends on
      increases in [Ca2+]i.

PMID- 9245517
TI  - Comparative effects of insulin on the activation of the Raf/Mos-dependent MAP
      kinase cascade in vitellogenic versus postvitellogenic Xenopus oocytes.
AB  - Xenopus postvitellogenic oocytes resume meiosis in vitro upon exposure to insulin
      or insulin-like growth factor 1 (IGF-1) via a ras-dependent pathway, whereas
      stage IV (600 micron < diameter < 1000 micron) oocytes cannot. The aim of the
      present study was to determine which event(s) of the transduction pathway from
      IGF-1 receptor to maturation-promoting factor (MPF) activation is deficient in
      the small, vitellogenic, oocytes to explain their inability to undergo germinal
      vesicle breakdown (GVB) after insulin treatment. We thus analyzed the effect of
      insulin on the Ras/Raf-dependent mitogen-activated protein kinase cascade because
      of its crucial role prior to MPF activation. The effect of insulin on pp39mos
      synthesis in stage IV oocytes was also studied since this protein kinase
      participates in the mitogen-activated protein kinase (MAPK) pathway as a MAPKK
      kinase like Raf. Contrary to what is observed in postvitellogenic oocytes, MAPK
      was not activated in insulin-treated stage IV oocytes even 20 hr after the
      stimulation. This was not caused by the absence of MAPK activators like MEK
      (MAPKK), Raf, or Ras, but rather by the inability of insulin to activate Ras.
      Interestingly, injection of constitutively active raf mRNA as well as oncogenic
      Ras protein, Ha-Ras lys12, in stage IV oocytes resulted in MAPK activation,
      whereas neither Mos accumulation nor GVB occurred, suggesting that the Ras -->
      Raf --> MAPKK --> MAPK cascade was functional but that MAPK activation alone was
      not sufficient for the mitogenic signal to proceed further down in the pathway
      leading to MPF activation. Treatment of stage IV oocytes with insulin did not
      stimulate Mos synthesis either, indicating a dysfunction in the "Mos synthesis
      machinery." The present results show that incompetence of Xenopus stage IV
      oocytes to activate MPF in response to insulin is primarily due to the inability
      of the peptide to activate Ras and to stimulate pp39mos synthesis and secondarily
      to a deficiency in the mitogenic pathway that connects MAPK to MPF activation.

PMID- 9245518
TI  - Impaired mammary gland development and function in mice lacking LAR receptor-like
      tyrosine phosphatase activity.
AB  - The LAR receptor-like protein tyrosine phosphatase is composed of two
      intracellular tyrosine phosphatase domains and a cell adhesion molecule-like
      extracellular region containing three immunoglubulin-like domains in combination
      with eight fibronectin type-III-like repeats. This architecture suggests that LAR
      may function in cellular signalling by the regulation of tyrosine phosphorylation
      through cell-cell or cell-matrix interactions. We used gene targeting in mouse
      embryonic stem cells to generate mice lacking sequences encoding both LAR
      phosphatase domains. Northern blot analysis of various tissues revealed the
      presence of a truncated LAR mRNA lacking the cytoplasmic tyrosine phosphatase
      domains and indicated that this LAR mutation is not accompanied by obvious
      changes in the expression levels of one of the LAR-like receptor tyrosine
      phosphatases PTPdelta or PTPsigma. LAR-/- mice develop and grow normally and
      display no appreciable histological tissue abnormalities. However, upon breeding
      we observed an abnormal neonatal death rate for pups from LAR-/- females. Mammary
      glands of LAR-/- females were incapable of delivering milk due to an impaired
      terminal differentiation of alveoli at late pregnancy. As a result, the glands
      failed to switch to a lactational state and showed a rapid involution postpartum.
      In wild-type mice, LAR expression is regulated during pregnancy reaching maximum
      levels around Day 16 of gestation. Taken together, these findings suggest an
      important role for LAR-mediated signalling in mammary gland development and
      function.

PMID- 9245519
TI  - Developmental potential of rat L6 myoblasts in vivo following injection into
      regenerating muscles.
AB  - To examine the relative importance of myoblast lineage and environmental
      influences on the development of muscle fiber types in vivo, the phenotype of
      muscle fibers formed from rat L6 myoblasts was examined following their injection
      into different regenerating adult muscles. Myoblasts were infected with a
      retroviral vector carrying a LacZ reporter gene and their fate in vivo was
      examined using a panel of antibodies against various myosin heavy chain (MyHC)
      isoforms. Since L6 myoblasts express IIX MyHC following differentiation in vitro,
      we wanted to determine if they would form IIX muscle fibers in vivo and whether
      innervation would alter this fate. Following injection, L6 cells either fused
      with each other to form homotypic fibers or fused with host muscle cells to form
      heterotypic fibers. Initially, homotypic fibers expressed embryonic MyHC-similar
      to L6 myotubes in vitro. However, by 4 weeks postinjection IIX MyHC had replaced
      embryonic MyHC as the predominant isoform. Single fiber analysis using an
      antibody specific for NCAM indicated that this transition was independent of
      innervation. Analysis of heterotypic fibers resulting from the incorporation of
      donor L6 myoblasts into host fast IIA and IIB fibers revealed that L6-derived
      nuclei express embryonic and IIX MyHCs for up to 8 weeks postinjection, often as
      nuclear domains surrounding L6 nuclei. These results suggest that MyHC expression
      in muscle fibers derived from L6 myoblasts is regulated, in part, by intrinsic
      factors that limit the fiber type potential of these cells in vivo.

PMID- 9245520
TI  - Both myoblast lineage and innervation determine fiber type and are required for
      expression of the slow myosin heavy chain 2 gene.
AB  - Skeletal muscle fibers express members of the myosin heavy chain (MyHC) gene
      family in a fiber-type-specific manner. In avian skeletal muscle it is the
      expression of the slow MyHC isoforms that most clearly distinguishes slow- from
      fast-contracting fiber types. Two hypotheses have been proposed to explain fiber
      type-specific expression of distinct MyHC genes during development-an intrinsic
      mechanism based on the formation of different myogenic lineage(s) and an
      extrinsic, innervation-dependent mechanism. We developed a cell culture model
      system in which both mechanisms were evaluated during fetal muscle development.
      Myoblasts isolated from prospective fast (pectoralis major) or slow (medial
      adductor) fetal chick muscles formed muscle fibers in cell culture, none of which
      expressed slow MyHC genes. By contrast, when muscle fibers formed from myoblasts
      derived from the slow muscle were cocultured with neural tube, the muscle fibers
      expressed a slow MyHC gene, while muscle fibers formed from myoblasts of fast
      muscle origin continued to express only fast MyHC. Motor endplates formed on the
      fibers derived from myoblasts of both fast and slow muscle origin in cocultures,
      and slow MyHC gene expression did not occur when neuromuscular transmission or
      depolarization was blocked. We have cloned the slow MyHC gene that is expressed
      in response to innervation and identified it as the slow MyHC 2 gene, the
      predominant adult slow isoform. cDNAs encoding portions of the three slow myosin
      heavy chain genes (MyHC1, slow MyHC 2, and slow MyHC 3) were isolated. Only slow
      MyHC 2 mRNA was demonstrated to be abundant in the cocultures of neural tube and
      muscle fibers derived from myoblasts of slow muscle origin. Thus, expression of
      the slow MyHC 2 gene in this in vitro system indicates that formation of slow
      muscle fiber types is dependent on both myoblast lineage (intrinsic mechanisms)
      and innervation (extrinsic mechanisms), and suggests neither mechanism alone is
      sufficient to explain formation of muscle fibers of different types during fetal
      development.

PMID- 9245521
TI  - Asymmetric expression of Notch/Delta/Serrate is associated with the anterior
      posterior axis of feather buds.
AB  - We studied the roles of Notch, Delta, and Serrate in vertebrate epithelial
      appendage morphogenesis using feather as a model and found the following. (1) C
      Notch-1, C-Delta-1, and C-Serrate-1 are not expressed at the early placode stage
      and are therefore not involved in the determination of bud versus interbud
      compartments. (2) From symmetric short buds to asymmetric long buds, C-Delta-1
      and C-Serrate-1 are expressed in the posterior bud mesenchyme in a nested
      fashion, while C-Notch-1 is expressed as a stripe perpendicular to the anterior
      posterior (A-P) axis and positioned posterior to the midpoint. (3) Epithelial
      mesenchymal recombination with rotation led to the disappearance of these genes
      followed by their reappearance with new positions appearing to predict their new
      morphological orientation. (4) Conditions leading to branched buds (e.g.,
      recombination of later buds) show polarized staining patterns before branching
      occurs. (5) Conditions leading to symmetrical round buds (e.g., treated with the
      protein kinase A agonist forskolin) suppress expression of all three genes. These
      results lead us to hypothesize that Notch, Delta, and Serrate are involved in
      establishing the A-P asymmetry of feather buds.

PMID- 9245522
TI  - Primary structure and bioactivity of bullfrog calcitonin.
AB  - Calcitonin was isolated from the bullfrog, Rana catesbeiana, and the first amino
      acid sequence of an amphibian calcitonin was determined to be Cys-Ser-Gly-Leu-Ser
      Thr-Cys-Ala-Leu-Met-Lys-Leu-Ser-Gln-Asp-Leu-His- Arg-Phe-Asn-Ser-Tyr-Pro-Arg-Thr
      Asn-Val-Gly-Ala-Gly-Thr-Pro-NH2. Some portions of this sequence are specific to
      bullfrog calcitonin, and other portions are similar both to teleost calcitonins
      and to mammalian calcitonins. Administration of 5 pmol of bullfrog calcitonin to
      rats revealed a hypocalcemic potency similar to that of salmon calcitonin, at
      least for the first 3 hr.

PMID- 9245523
TI  - Maternal thyroid hormones in Japanese quail eggs and their influence on embryonic
      development.
AB  - We addressed the relationship between the thyroid status of hens and the thyroid
      hormone content of their eggs, as well as the influences of egg hormones on
      embryonic development. Methods for measuring thyroid hormones in egg yolk were
      verified by demonstrating consistency in the recovery of yolk thyroid hormones
      following a methanol/chloroform extraction and in the measurement of thyroid
      hormones by RIA for a range of hormone concentrations in yolk extracts. Untreated
      hens produced eggs with yolk thyroxine (T4) concentrations that were low relative
      to plasma T4, but yolk triiodothyronine (T3) concentrations comparable to those
      of plasma. Hens dosed twice daily with T4 (1 or 3x the daily thyroid secretion
      rate, TSR, of T4 per dose) had significantly higher plasma and egg yolk T4
      concentrations than did control hens dosed with saline. In general, the T4
      concentration of egg yolk varied with the thyroid status of the hen. When the
      relationship between each hen's plasma T4 and the yolk T4 concentration of her
      eggs was examined, hens appeared to regulate T4 deposition into yolk at "levels"
      characteristic of the "levels" of thyroid status produced by the different doses
      of T4. Embryonic pelvic cartilage, a thyroid hormone-responsive tissue, showed
      enhanced growth and differentiation in embryos from eggs of hens given the
      highest dose of T4. Specifically, alkaline phosphatase activity (a marker of
      differentiation) and pelvic cartilage wet and dry weights were significantly
      greater in embryos from high T4 eggs (hens on the 3x TSR dose) than those in
      controls. However, embryos from high T4 eggs did not differ in general body
      growth (body weight, length, and general morphology) or hatchability compared to
      controls. In a single T3 experiment, hens were dosed twice daily with 1 microg
      T3. The embryos from eggs of these hens had accelerated
      differentiation/maturation of pelvic cartilages (sampled at Day 12) compared to
      those from control eggs; body growth did not differ from that of controls.

PMID- 9245524
TI  - A role for pancreatic hormones in the regulation of autumnal fat deposition of
      the garden warbler (Sylvia borin)?
AB  - Glucagon and insulin were measured by heterologous immunoassays in plasma samples
      of 17 garden warblers (Sylvia borin) kept under constant ad libitum or fasting
      refeeding conditions during the migratory season from September to May. Plasma
      levels of key metabolic indicators (glucose, triglycerides, cholesterol, and free
      fatty acids) were measured every 2 weeks. Measurements of the two hormones concur
      with the general assumption of a higher glucagon:insulin ratio, indicating a more
      pronounced catabolism in birds than in mammals. The concentrations of both
      hormones varied (insulin: 0.7-7.7 microIU/ml, n = 66; glucagon: 0.4-4.5 ng/ml, n
      = 99), but differences between mean values per month were significant only for
      glucagon. Neither hormone titer correlated with either the seasonal or a fasting
      refeeding-induced body mass cycle. However, there was a positive correlation
      between food intake, changes in body mass, and plasma triglycerides and insulin;
      in contrast, there was a negative relationship with the glucagon:insulin ratio.
      Glucagon showed only a small negative relationship to plasma glucose and
      cholesterol, but correlated directly more closely with plasma free fatty acids.
      The present data support the fact that glucagon is more lypolytic in birds than
      in mammals. Pancreatic hormones are suggested to participate in the regulation of
      premigratory hyperphagia and hyperlipemia.

PMID- 9245525
TI  - Effects of 17alpha,20beta-dihydroxy-4-pregnen-3-one on cortisol production by
      rainbow trout interrenal tissue in vitro.
AB  - Physiological levels of 17alpha,20beta-dihydroxy-4-pregnen-3-one (17, 20-P)
      stimulated time- and dose-dependent increases in cortisol production by rainbow
      trout (Oncorhynchus mykiss) interrenal tissue cultured in vitro. Significant
      stimulation occurred in response to 100, 300, and 1000 ng/ml of 17,20-P. Lower
      doses were ineffective. Elevated cortisol levels were observed 1 hr after
      addition of 300 ng/ml 17,20-P. No additive or synergistic interaction was evident
      between human adrenocorticotropin fragment 1-24 (ACTH1-24) and 17, 20-P in
      stimulating cortisol secretion, although 300 ng/ml 17,20-P could further enhance
      cortisol production above levels already stimulated by 300 ng/ml ACTH. 17alpha,
      20alpha-dihydroxy-4-pregnen-3-one also stimulated cortisol secretion, but was
      only half as effective as 17,20-P. Estradiol-17beta, testosterone, and 11
      ketotestosterone had no effect on cortisol secretion. Inhibitors of mRNA and
      protein synthesis had no effect on 17,20-P-stimulated cortisol production.
      Radiotracer studies demonstrated that the bioconversion of 17,20-P to cortisol
      could fully account for the cortisol produced by the interrenal in response to
      17,20-P and demonstrated that rainbow trout interrenal cells contain an active
      20beta-hydroxysteroid dehydrogenase. These data suggest that 17,20-P may be a
      regulator of cortisol production during the periovulatory period in salmonid
      fishes.

PMID- 9245526
TI  - Cloning and sequence analysis of a cDNA for the beta subunit of chicken thyroid
      stimulating hormone.
AB  - The beta subunit of thyroid-stimulating hormone (TSHbeta) has been isolated and
      sequenced in many species, including several mammals and the frog, but not in any
      avian species. Therefore, the objective of this study was to isolate and sequence
      a cDNA for chicken TSHbeta. Degenerate oligonucleotide primers were designed,
      based on conserved regions of TSHbeta from four other species, and used for
      reverse transcription and polymerase chain reaction amplification of a cDNA
      fragment from total cellular RNA of pituitary glands from 7-day-old chicks. The
      remaining sequence was completed by rapid amplification of cDNA ends. The
      predicted amino acid sequence was 70. 4% identical between bovine and chicken,
      69.6% identical between chicken and rat, and 57.4% identical between chicken and
      frog. To test for tissue specificity of the cDNA, total cellular RNA samples from
      testicle, liver, pituitary, lung, and heart were analyzed by Northern blot. The
      32P-labeled antisense riboprobe hybridized to an RNA species of approximately 600
      700 bases in pituitary RNA alone, corresponding with the length of TSHbeta mRNA
      in other species. Gene expression in Day 1 posthatch chickens was then analyzed
      by ribonuclease protection assay. Anterior pituitary cells of Day 1 chickens were
      treated for 20 to 24 hr in serum-free medium alone or with medium containing
      either thyrotropin-releasing hormone (TRH) (10(-8) M) or triiodothyronine (T3)
      (10(-9) M). The RNA was then harvested from these cells and hybridized with a 32P
      labeled antisense riboprobe. Treatment with TRH had no effect on TSHbeta mRNA
      levels, while T3 significantly decreased (P < 0.05; n = 6 trials) TSHbeta mRNA
      levels by 45%. Taken together these results indicate that the cDNA sequence
      derived represents chicken TSHbeta mRNA, and that TSHbeta gene expression is
      downregulated by thyroid hormones as it is in mammals.

PMID- 9245527
TI  - Yolk steroids decline during sexual differentiation in the alligator.
AB  - The leading explanation of temperature-dependent sex determination (TSD) in
      reptiles postulates that (1) ovarian differentiation is directed by estrogen and
      that (2) estrogen is synthesized in the developing gonad following induction of
      aromatase expression. However, the source of steroid substrate for aromatization
      has not yet been identified. In addition, sex ratios vary as a function of
      clutch, but such biases are as yet unexplained. To address these issues, we
      measured estradiol, testosterone, and androstenedione in yolks of the American
      alligator (Alligator mississippiensis) before, during, and after the period of
      gonadal differentiation in this TSD species. Eggs were collected from a wild
      population in Louisiana and were incubated at male- and female-determining
      constant temperatures in the lab, as well as at intermediate temperatures that
      produced both sexes. Steroids were assayed in yolk extracts after celite column
      chromatography. All three steroids were found to be in the range of
      nanograms/gram of yolk at stage 16. Androstenedione was the predominant steroid,
      2- to 3-fold higher in concentration than estradiol and 15- to 20-fold higher
      than testosterone. The levels of these steroids declined (5- to 30-fold) between
      stages 16 and 25, most markedly between stages 21 and 23, regardless of
      incubation temperature. The chronology of this sharp decline in steroid levels in
      our study coincides with the timing of gonadal differentiation in this species,
      between stages 21 to 23 based on previous reports. Estradiol levels in yolks
      differed by 3-fold in some clutches relative to others, whereas, no clutch
      differences were apparent for either androstenedione or testosterone. These data
      demonstrate that alligator yolk contains high concentrations of two steroid
      substrates utilized for estrogen synthesis, as well as significant quantities of
      estradiol itself. We hypothesize that estradiol levels in yolk provide a steroid
      background, variable among and within clutches, on which gonadal development is
      initiated and proceeds. As a consequence, we suggest that yolk provides an
      epigenetic maternal contribution that modulates the effect of incubation
      temperature on hatchling sex.

PMID- 9245528
TI  - The fate of newly synthesized hormone from neuroendocrine cells of Aplysia.
AB  - The neuroendocrine bag cells from Aplysia control reproductive functions through
      the regulated release of egg-laying hormone (ELH). The purposes of this study
      were to investigate (1) if synthesis of ELH in bag cells compensates for the
      release and degradation of the hormone, (2) the ratio of released to stored ELH,
      (3) the fate of newly synthesized ELH and its relative contribution to the
      overall pattern of ELH secretion, and (4) the consequences of blocking protein
      synthesis in bag cells on the pattern of ELH secretion and subsequent
      reproductive function. Excised bag cells were incubated with [3H]leucine to
      radiolabel newly synthesized ELH and were then electrically stimulated to trigger
      secretion of the hormone on 4 successive days, mimicking bag cell activities
      during the breeding season. Samples of bag cell secretion were collected; total
      (new and old) and radiolabeled (new) ELH levels were determined. The results
      showed that ELH synthesis could not keep up with the daily loss of ELH through
      release and degradation, but the ratio of released to stored ELH remained
      constant over the 4-day study. In addition, releasable ELH was secreted
      preferentially within 24 hr after it was synthesized. Blocking protein synthesis
      resulted in a 50% decrease in total ELH released, suggesting that newly
      synthesized ELH contributes to half of the total ELH secreted. Furthermore, this
      lowered level of total ELH, i.e., older ELH alone, was not sufficient to
      stimulate egg laying in Aplysia, indicating that the contribution of newly
      synthesized ELH was physiologically relevant.

PMID- 9245529
TI  - The effect of food intake from two weeks of age to sexual maturity on plasma
      growth hormone, insulin-like growth factor-I, insulin-like growth factor-binding
      proteins, and thyroid hormones in female broiler breeder chickens.
AB  - Plasma concentrations of metabolic hormones were determined in broiler breeders
      fed on three quantitatively different food regimes in the period prior to sexual
      maturity. The first group was fed ad libitum, the second group was fed a
      restricted quantity of food, and the third group was restricted to obtain an
      intermediate body weight between those of the first two groups. In food
      restricted birds, insulin-like growth factor-I (IGF-I) reached the highest plasma
      concentrations at 8 and 14 weeks of age in contrast with levels in the fully fed
      animals, in which only one maximum value was observed at 10 weeks. From 14 weeks
      on, IGF-I concentrations remained higher in the restricted groups compared to the
      ad libitum group. Three IGF-binding proteins with molecular masses of 28, 34, and
      40.5 kDa were detected in the plasma of broiler breeders after Western ligand
      blotting. The concentrations of the 28- and 34-kDa IGF-binding protein bands
      showed an age-related pattern in all groups. The intensity of these bands was
      higher in the restricted groups compared to that of the bands for the fully fed
      animals. No significant differences between the groups could be observed in the
      intensity of the 40.5-kDa band. Food restriction resulted in higher plasma
      concentrations of GH and T4 compared with levels in the fully fed animals. T3
      plasma concentrations were higher in the ad libitum fed group than in the
      restricted groups. In all groups, GH and T3 concentrations decreased with
      advancing age, whereas T4 increased during the same period. This is the first
      description of the effects of long-term food restriction prior to the onset of
      sexual maturity on circulating levels of hormones of the somatotrophic and the
      thyrotrophic axes in female broiler breeders. The interrelationship between GH,
      IGF-I, IGFBPs, and thyroid hormone concentrations and differences in subsequent
      reproductive performance of differently fed broiler breeders requires further
      investigation.

PMID- 9245530
TI  - Effects of epidermal growth factor on isolated digestive gland cells from
      mussels.
AB  - Effects of epidermal growth factor (EGF) and possible mechanisms of EGF-mediated
      signal transduction were investigated in isolated cells of the digestive gland of
      the mussel (Mytilus galloprovincialis Lam. ). EGF induced a cytosolic Ca2+
      transient and subsequently stimulated DNA synthesis; both effects were dose
      dependent in the nanomolar range and inhibited by pretreatment with an inhibitor
      of tyrosine kinase activity, suggesting specific EGFR-like receptors. The EGF
      induced cytosolic Ca2+ transient was mainly due to a Ca2+ influx through the
      plasma membrane, possibly involving voltage-insensitive Ca2+ channels. Such a
      Ca2+ response was abolished by pretreatment with indomethacin and NDGA,
      inhibitors of arachidonic acid metabolism; similarly, the EGF-stimulated increase
      in DNA synthesis was significantly reduced. Indomethacin, a cyclooxygenase
      inhibitor, had the greatest effect on both EGF-induced responses. Results suggest
      the presence of EGF-responsive cells in the mussel digestive gland. A possible
      role for arachidonic acid and its metabolites in mediating the effects of EGF is
      also indicated.

PMID- 9245531
TI  - Guanylyl cyclase receptors and guanylin-like peptides in reptilian intestine.
AB  - Receptors for guanylin and uroguanylin were identified on the mucosal surface of
      enterocytes lining the intestine of the bobtail skink (Tiliqua rugosa), king's
      skink (Egernia kingii), and knight anole (Anolis equestris) by receptor
      autoradiography using 125I-ST (Escherichia coli heat-stable enterotoxin) as the
      radioligand. Specific, high-affinity binding of 125I-ST to receptors was found on
      the microvillus border of enterocytes and little or no specific binding of 125I
      ST was observed in other strata comprising the gut wall. The American alligator
      (Alligator mississippensis) also exhibited receptor binding, but unlike the other
      three species had relatively high levels of apparent nonspecific binding. A
      comparison of intestinal cGMP accumulation responses between the American
      alligator and the knight anole demonstrated a greater magnitude of cGMP responses
      to ST and guanylin in vitro in the knight anole relative to the tissue cGMP
      accumulation responses of alligators. Treatment with ST resulted in markedly
      greater tissue cGMP accumulation responses in both species compared to treatment
      with guanylin. To complete a paracrine signaling pathway in reptilian intestine,
      guanylin-like peptides that stimulated cGMP accumulation in human T84 intestinal
      cells were isolated from the intestinal mucosa of alligators. We conclude that
      functional receptor-guanylyl cyclases and one or more endogenous
      guanylin/uroguanylin-like peptides occur in the intestinal tract of reptiles as
      well as in the intestines of mammals and birds. Thus, higher vertebrates have a
      conserved signaling pathway that regulates intestinal function through the first
      messenger peptides, guanylin and/or uroguanylin, and the intracellular second
      messenger, cGMP.

PMID- 9245532
TI  - Changes in thyroid hormone concentrations and total contents through ontogeny in
      three anuran species: evidence for daily cycles.
AB  - Three anuran species (Rana perezi, Xenopus laevis, and Bufo calamita) of
      different phylogenetic origins and ecological habitats have been studied during
      ontogeny with respect to day/night changes in whole-body concentrations and total
      content of extrathyroidal thyroxine (T4) and triiodothyronine (T3). There were no
      significant day/night changes in thyroid hormones (TH) during embryonic stages.
      Daily cycles in TH with higher nocturnal values appeared during premetamorphosis
      in R. perezi and X. laevis. Cyclicity disappears for T3, while it is reversed for
      T4, in prometamorphic R. perezi and X. laevis. In contrast, there were
      significantly higher T3 (0.74 +/- 0.13 ng/g) and T4 (2.08 +/- 0.54 ng/g) levels
      at night in prometamorphic B. calamita. Significant daily changes in T3 and T4
      with higher nocturnal values (T3, 788.29 +/- 118.38 pg/g; T4, 1.95 +/- 0.4 ng/g)
      were again seen in X. laevis at the end of climax, while in B. calamita low TH
      values appeared at early scotophase and there were no significant changes in R.
      perezi at this time. Similar daily profiles were observed for TH whole-body
      concentrations and total contents.

PMID- 9245534
TI  - Cloning and Expression Pattern of a Second
AB  - Complementary DNAs (cDNAs) encoding [Trp7Leu8]GnRH (sGnRH) and [His5Trp7Tyr8]GnRH
      (cGnRH-II) peptides have been isolated from the brain of goldfish (X. W. Lin and
      R. E. Peter, 1996, Gen. Comp. Endocrinol. 101, 282-296). In the present study we
      report the isolation of a second cDNA encoding cGnRH-II peptide in the brain of
      goldfish using reverse transcription (RT) and rapid amplification of cDNA ends.
      There is an overall 79.7% nucleotide sequence similarity between the two cGnRH-II
      cDNAs, with 65.3, 91.2, and 76.3% similarity between the 5'-untranslated regions,
      coding regions, and 3'-untranslated regions, respectively, of the two cGnRH-II
      cDNAs. Comparison of the two cGnRH-II precursors shows 87.2% amino acid
      similarity. The presence of two cGnRH-II genes was confirmed by the sequence
      analysis of the introns between exon II and exon III of the two cGnRH-II genes.
      Results indicate that the intron of the two cGnRH-II genes shows a high
      divergence in size and sequence, but contains the same splice junction.
      Expression of the two cGnRH-II mRNAs was detected by RT-polymerase chain reaction
      assay and Southern blot analysis in all five grossly dissected brain areas,
      olfactory bulbs and tracts, telencephalon, hypothalamus, optic tectum-thalamus,
      and posterior brain. However, there was a difference in apparent intensity of
      hybridization signal for the two cGnRH-II mRNAs in all brain areas, suggesting a
      difference of expression levels. sGnRH mRNA was detected in the olfactory bulbs,
      telencephalon, and hypothalamus, but not in midbrain and posterior brain areas.
      The present finding of duplicate cDNAs and genes for cGnRH-II in goldfish is in
      agreement with the recent tetraploidization in this species.

PMID- 9245533
TI  - The thyroid hormone, 3,5,3'-triiodothyronine, is a negative modulator of domestic
      fowl (Gallus gallus domesticus) adrenal steroidogenic function.
AB  - Previous work with chickens (Gallus gallus domesticus) suggests a relationship
      between depressed thyroid hormone status and enhanced adrenal steroidogenic
      function. In addition, in hypophysectomized chickens, replacement of the thyroid
      hormone, 3,5,3'-triiodothyronine (T3), maintains chicken adrenal steroidogenic
      cell sensitivity to adrenocorticotropin (ACTH) but decreases steroidogenic
      capacity further than that due to hypophysectomy alone. The present in vivo and
      in vitro studies were conducted to determine the influence of thyroid status and
      T3 per se on avian adrenal steroidogenic function. Chicks (1 day old) were
      thyroidectomized using combined surgical and chemical (6-propyl-2-thiouracil)
      treatments and were administered a replacement dose of T3 (0, 1.5, 4.5, 15, and
      45 microg/kg body wt/day) for 5 weeks. Whereas thyroidectomy (TX) decreased
      adrenal weight (-20%), it increased relative adrenal weight (mg/100 g body
      weight) (+171%), trunk plasma corticosterone (+880%), and aldosterone (+124%). In
      addition, TX increased basal, maximal ACTH-induced, maximal 8-bromo-cyclic AMP
      induced, and maximal 25-hydroxycholesterol-supported corticosterone production
      (+520, +93, +124, and +195%, respectively) and aldosterone production (+578,
      +288, +280, and +275%, respectively) by isolated adrenal steroidogenic cells. T3,
      in a dose-dependent manner, reversed the effects of TX on these in vivo and in
      vitro parameters of adrenal steroidogenic function. Restoration of most of these
      parameters to those in the sham-treated control was attained with 4.5-15
      microg/kg body wt/day. Although some of the effects of TX and T3 replacement on
      adrenal steroidogenic function may have been mediated through changes in
      circulating levels of ACTH, other data suggest a direct effect on adrenal
      steroidogenic cell function. Adrenal steroidogenic cells from sham-treated and TX
      birds were preincubated (0, 4, and 12 hr) with various concentrations of T3 (0,
      0.3, 3, and 30 nM), washed, and then incubated for an additional 2 hr in medium
      containing the same respective concentrations of T3, with or without a maximal
      steroidogenic concentration of ACTH (100 nM). T3 had no acute effects on TX
      dependent enhancement of adrenal steroidogenic cell function (2-hr incubation).
      However, with preincubation (4 and 12 hr), T3 inhibited basal and maximal ACTH
      induced corticosterone production in a dose-dependent manner. This concentration
      dependent, direct effect of T3 was not observed with cells from sham-treated
      birds. In addition, the ostensibly inactive thyroid hormone metabolite, 3,3',5'
      triiodothyronine [reverse T3; 30 nM], was without effect. Taken collectively,
      these studies indicate that T3 is a direct negative modulator of avian adrenal
      steroidogenic function.

PMID- 9245535
TI  - Male morphs in tree lizards have different testosterone responses to elevated
      levels of corticosterone.
AB  - Changes in circulating glucocorticoid and androgen levels mediate agonistic
      behaviors in many vertebrates. Individual variation in the magnitude of the
      glucocorticoid response to stressful stimuli, the negative effects of elevated
      glucocorticoid levels on androgen levels, or both could mediate individual
      differences in subsequent agonistic behavior. In a series of previous studies, we
      found that both alternative male reproductive morphs in the tree lizard,
      Urosaurus ornatus, can exhibit elevated levels of plasma corticosterone following
      male-male encounters, but that the territorial morph appears less likely to
      exhibit coincident decreases in plasma testosterone. Two studies tested the
      hypothesis that the two morphs differ in the degree to which testosterone levels
      are influenced by elevated corticosterone levels. In the first study, physically
      restraining males elicited endogenous elevations of circulating corticosterone
      levels. Testosterone levels were significantly negatively correlated with
      corticosterone levels in the nonterritorial morph, but there was no correlation
      between levels of the two steroids in territorial males. In the second study,
      corticosterone levels were artificially elevated in free-living male tree lizards
      using a noninvasive dermal patch. This exogenous elevation of corticosterone
      significantly depressed testosterone levels in both morphs, but it produced a
      significantly greater depression in the nonterritorial morph. Nonterritorial
      males appear to be more sensitive than territorial males to the testosterone
      suppressing effects of elevated circulating levels of corticosterone. This
      difference between the morphs in the effects of a stress hormone on the
      reproductive axis may be a fundamental part of the mechanism (1) underlying
      behavioral tactic switching within the nonterritorial morph or (2) contributing
      to behavioral differences between the morphs.

PMID- 9245537
TI  - Reply

PMID- 9245538
TI  - EDITORIAL STATEMENT

PMID- 9245536
TI  - Estrogen induction of plasma vitellogenin in the Kemp's ridley sea turtle
      (Lepidochelys kempi).
AB  - Estrogen stimulation of the production of teh yolk protein precursor vitellogenin
      was demonstrated in immature Kemp's ridley sea turtles. 17beta-Estradiol
      injection elicited an increase in serum estrogen, protein, protein phosphorus,
      and total calcium within 7 days. Associated with these changes was the appearance
      of a single, dimethylformamide-precipitable, 205-kDa estradiol-induced serum
      protein, which became the predominant serum protein identified by polyacrylamide
      gel electrophoresis. The effects of estradiol injection were maintained for 3
      months following termination of estradiol administration, despite a decline in
      serum estrogen levels. Although studies in other species have indicated that
      changes in circulating vitellogenin levels can influence thyroid hormone
      transport, no changes were observed throughout the study in total blood levels of
      thyroxine or triiodothyronine or protein binding of these hormones. We conclude
      that in the immature Kemp's ridley estrogen induces the synthesis and secretion
      of a vitellogenin which resembles that of other reptiles, but which does not
      influence thyroid hormone transport. The prolonged presence of vitellogenin in
      the blood may be due to a lack of an active ovarian uptake mechanism in these
      immature animals.

PMID- 9245539
TI  - The Th1/Th2 dichotomy, hsp60 autoimmunity, and type I diabetes.
AB  - This paper presents some questions and issues regarding the concept of the
      Th1/Th2 dichotomy and summarizes results using an hsp60 peptide to treat the
      spontaneous autoimmune process of diabetes in NOD mice.

PMID- 9245540
TI  - Processing of IgA aggregates in a rat model of chronic liver disease.
AB  - Heavy alcohol intake and/or lipotrope-deficient diet induced hepatocellular
      injury and mesangial deposition of IgA and often IgG in Lewis rats. The
      experimental animals showing more severe urinary abnormalities and histologic
      damage in the glomeruli had increased levels of IgA antibodies to dietary
      antigens and altered intestinal permeability. Based on human studies, the
      prolonged circulation of IgA-containing complexes associated with the liver
      disease could be envisaged as important for the development of mesangial IgA
      deposits. In order to verify this hypothesis, four groups (G) of Lewis rats were
      studied: G1 received thrice a weak an intragastric infusion of 1.5 ml/100 g body
      wt of whiskey; G2 rats were nourished with lipotrope-deficient diet; G3 rats were
      given both whiskey and LD diet; G4 rats were nourished with regular chow. After
      12 weeks, heat-aggregated rat monomeric IgA was labeled with 133I and
      intravenously injected. Three control subgroups of rats, one given whiskey, one
      nourished with LD diet, and one with regular chow, were injected with
      radiolabeled heat-aggregated rat IgG. A large field-of-view digital gamma camera,
      equipped with an ultra-high-resolution collimator and interfaced to a dedicated
      computer, was used to analyze tracer kinetics and fate. The liver was the main
      organ involved in clearance of both test probes. The hepatic mean transit (MTT)
      was 11.4 +/- 11 min in G1 (proteinuria of 6.9 +/- 1.41 mg/day and hematuria
      +/+2), 221 +/- 19 min in G2 (proteinuria 9.1 +/- 0.64 mg/day and hematuria
      +2/+3), and 230 +/- 15 min in G3 (proteinuria 9.5 +/- 0.58 mg/day and hematuria
      +2/+3). In each case MTT value was found to be significantly prolonged compared
      to G4 (85 +/- 4 min). The multiple regression analysis showed that MTT values,
      proteinuria, and hematuria were significantly correlated (P < 0.01). Controls had
      trace amount proteinuria (0.82 +/- 0.17 mg/day, significantly lower than for each
      study group, P < 0.08) and undetectable hematuria. Similar results were obtained
      in control rats injected with aggregated IgG; i.e., MTT values were more
      prolonged in rats given whiskey or LD diet than normally nourished rats (P <
      0.01). The lipotrope-deficient diet and the chronic alcohol abuse per se seem to
      lead to critical changes in hepatic uptake and catabolism of both an IgA and an
      IgG aggregate, which could account in turn for the reported appearance of renal
      immunoglobulin deposits in this experimental model. Due to the comparable delay
      in removal of IgA and IgG probes in equally nourished animals, additional factors
      are likely to be involved in the prominent deposition of IgA.

PMID- 9245541
TI  - Serotonin modulates immune function in T cells from HIV-seropositive subjects.
AB  - We have shown earlier increased intracellular levels of cAMP in peripheral
      lymphocytes from HIV-seropositive subjects and that a chemically induced decrease
      in this level increases cell proliferation and cytotoxicity. Others have shown
      that serotonin indirectly decreases intracellular cAMP levels in normal
      peripheral lymphocytes. In this study, we show that addition of serotonin
      decreases intracellular levels of cAMP in lymphocytes from HIV-seropositive
      subjects and significantly increases the proliferative capacity in vitro.
      However, the effect of serotonin varies with the initial proliferative response;
      e.g., these with the highest initial responses have the highest increases. An
      increase in IL-2 production may be a part of this mechanism since addition of
      serotonin to in vitro cultures of PHA-stimulated cells increases the expression
      of mRNA for IL-2 and IFN-gamma. The effect on lymphocyte proliferation was most
      likely mediated through the serotonin 5HT1a receptor because similar results
      could be obtained by using DPAT, a specific activator of this receptor. Changes
      in the expression of 5HT1a receptors as judged by the expression of mRNA could
      not explain why serotonin in vitro had a stronger enhancing effect on cell
      proliferation in some HIV-seropositive individuals than in others.

PMID- 9245542
TI  - Analysis of blood lymphocyte subsets in children living on territory that
      received high amounts of fallout from Chernobyl accident.
AB  - The major lymphocyte subsets in the peripheral blood were assessed in 120
      children 6-13 years old living on areas that received high levels of
      radioactivity as fallout after the Chernobyl nuclear power plant accident.
      Seventy-one of the children were suffering from recurrent respiratory disease
      (RRDC) and 49 were not (non-RRDC). As controls, a total of 87 RRDC and non-RRDC
      living on noncontaminated areas were evaluated. We did not find significant
      differences in major lymphocyte subsets between the values in non-RRDC living on
      radionuclide-contaminated areas and noncontaminated areas. However, RRDC living
      on radionuclide-contaminated areas had a significantly lower percentage of CD3+ T
      and CD3+CD4+ T-helper/ inducer cells compared to control RRDC. Furthermore, the
      decrease in percentage of CD3+CD4+ cells was more profound in RRDC living in
      radiation-contaminated settlements with an average summary dose (ASD) Cs-137(134)
      and Sr-90 for the population > 1.0 mSv than in RRDC living in contaminated
      settlements with an ASD Cs-137(134) and Sr-90 < 1.0 mSv. These data indicated
      that long-time exposure to small doses of radiation could affect the immune
      system in children living around Chernobyl.

PMID- 9245543
TI  - Phenotypic features of selective T cell deficiency characterized by absence of
      CD8+ T lymphocytes and undetectable mRNA for ZAP-70 kinase.
AB  - Selective T cell deficiency is a rare immune deficiency characterized by the
      absence of CD8+ T lymphocytes and depressed/absent T cell function. This syndrome
      has been associated with mutations in the gene for ZAP-70, a tyrosine kinase that
      has profound effects on signaling via the T cell receptor. In this paper we
      describe a patient with selective T cell deficiency and certain phenotypic
      features that are unique among the small number of patients described. The
      patient had virtually absent T cell function, hypogammaglobulinemia, and no
      response to vaccination. The T lymphocytes failed to respond to mitogenic
      stimuli, even in the presence of exogenous interleukin 2. Similar to other
      patients with this disorder, the T cells were capable of proliferating when
      stimulated by pharmacologic agents such as phorbol ester and ionomycin. While
      peripheral blood T cells had limited capability to increase cytosolic Ca2+ levels
      in response to mitogenic stimulation, thymocytes responded to a large panel of
      antibodies and mitogens. This report broadens the spectrum of clinical
      presentations associated with selective T cell deficiency and, for the first
      time, compares the responses of both peripheral T cells and thymocytes. The data
      support the concept that the defect in signal transduction resulting from the
      absence of ZAP-70 is primarily manifested following export of T lymphocytes from
      the thymus and that selection of CDS-positive T cells is dependent on the
      presence of ZAP-70.

PMID- 9245544
TI  - Serum soluble CD23 but not IL8, IL10, GM-CSF, or IFN-gamma is elevated in
      patients with hepatitis C infection.
AB  - The increased frequency of autoantibodies and B cell non-Hodgkins lymphoma (B
      NHL) in hepatitis C virus (HCV) infection suggests dysregulated humoral immunity.
      Soluble CD23 (sCD23) is involved in B cell activation and proliferation and the
      serum levels are raised in autoimmune diseases and B cell lymphoproliferative
      disease. We compared the serum levels of sCD23 in patients with HCV infection
      with those in patients with alcoholic cirrhosis (AC) and in healthy controls.
      Serum levels of interleukin (IL) 8, IL10, granulocyte macrophage-colony
      stimulating factor, and interferon-gamma were assessed simultaneously to check
      for generalized nonspecific immune stimulation. In contrast to the essentially
      normal serum levels of these latter cytokines, the levels of sCD23 were raised in
      the patients with HCV compared to those with AC and the normal controls (medians
      34.0, 10.1, and 11.1 arbitrary units, respectively; HCV vs AC P < 0.0004, HCV vs
      controls P < 0.0001, AC vs controls P > 0.8). These results confirm HCV-induced
      humoral immune dysregulation and invite comparison with primary Sjogrens syndrome
      and Epstein-Barr virus infection, both of which are also associated with raised
      levels of serum sCD23, autoantibodies, and B-NHL.

PMID- 9245545
TI  - Immune system differences in men with hypo- or hypercholesterolemia.
AB  - Substantial epidemiologic evidence indicates that relative hypocholesterolemia in
      apparently healthy individuals is associated with increased subsequent mortality
      from cancer and other nonatherosclerotic causes of death. To test a hypothesis
      potentially underlying these unexplained associations, we evaluated whether
      individuals with hypo- and hypercholesterolemia differ in various enumerative and
      functional indices of the immune system. Nineteen healthy adult men with a mean
      age of 46 years and a mean total cholesterol concentration of 151 mg/dl
      constituted a low cholesterol group and were compared with 39 men of a similar
      age whose total cholesterol averaged 261 mg/dl. Relative to the high cholesterol
      group, hypocholesterolemic men had significantly fewer circulating lymphocytes,
      fewer total T cells, and fewer CD8+ cells (P's < 0.05). Trends toward fewer CD4+
      cells and less IL-2 release in response to PHA were also noted in the low,
      compared to the high, cholesterol group. The low and high cholesterol groups did
      not differ in number of B lymphocytes, level of PHA-induced proliferation, number
      of natural killer (NK) cells, or degree of NK cytotoxicity. These data provide
      preliminary evidence of immune system differences in healthy individuals with
      hypo- and hypercholesterolemia.

PMID- 9245546
TI  - The epitopic "fingerprint" of thyroid peroxidase-specific Fab isolated from a
      patient's thyroid gland by the combinatorial library approach resembles that of
      autoantibodies in the donor's serum.
AB  - A new thyroid peroxidase (TPO)-specific Fab (KM1) was obtained from an
      immunoglobulin gene combinatorial library of patient KM containing L chain genes
      amplified with a single "promiscuous" V kappa oligonucleotide primer. The KM1 L
      chain is encoded by a mutated B3 gene (V kappa IV family). Another mutated B3 L
      chain had been identified previously in a TPO-specific Fab (WR1.223) isolated
      from a different patient (WR). In contrast to patient KM, the WR L chains were
      amplified with a panel of V kappa family-specific primers. Both KM1 and WR1.223
      bind TPO with high affinity (approximately 1 x 10(-9) M) and interact with an
      epitope in the B domain of the TPO immunodominant region. TPO-specific Fab
      previously isolated from a WR combinatorial library constructed with the
      promiscuous V kappa primer recognised the TPO A domain and none used a B3-like L
      chain. Remarkably, for both patients, Fab isolated from L chains generated with
      the promiscuous V kappa primer had epitopic profiles similar to autoantibodies in
      the donor's serum (KM-B domain; WR-A domain). Our data indicate that the
      promiscuous primer preferentially amplifies the dominant L chain present in vivo.
      However, to obtain a relatively rare Fab (such as the B domain Fab from WR),
      family-specific kappa primers are required. These findings provide insight into
      the relationship between TPO autoantibody gene usage, epitopic recognition, and
      the effectiveness of the combinatorial library approach.

PMID- 9245547
TI  - Enhanced expression of CD31 and CD54 on tonsillar high endothelial venules in IgA
      nephropathy.
AB  - Abnormalities in the partition of IgA- and IgG-producing cells in the tonsils of
      patients with IgA nephropathy have been suggested to result from a dysregulation
      of cell trafficking and homing through high endothelial venules in this lymphoid
      tissue. In order to document such adhesion anomalies, we used the 36 monoclonal
      antibodies of the cell adhesion molecules subpanel of the Fifth International
      Workshop on Leukocyte Differentiation Antigens on frozen sections of tonsils from
      10 patients and 15 controls. This allowed us to describe the partition of cell
      adhesion molecules in human tonsils and to demonstrate a significant enhancement
      of CD31 and CD54 expression on high endothelial venules of tonsils from patients
      with IgA nephropathy. These observations are in keeping with the hypothesis of an
      increased lymphocyte recruitment in tonsils in this disease.

PMID- 9245548
TI  - Changes in bone mineral density in rat adjuvant arthritis.
AB  - This study demonstrates that systemic and local decreases in bone mineral density
      (BMD) occurred with Freund's complete adjuvant injection in the rat right footpad
      using dual energy X-ray absorptiometry. The rats were assigned to either adjuvant
      treated or non-treated control groups composed of eight animals each. There was
      significant decrease in BMD in the adjuvant group compared to the control group
      at the distal region of femur or proximal region of tibia on Day 7 post-adjuvant
      injection (P < 0.05). On the other hand, the femur or tibia of the noninjected
      side showed a smaller and delayed decrease in BMD than did the injected side.
      These decreases in BMD were seen in not only the trabecular but also the cortical
      bone. In addition, the vertebrae also showed delayed but significant decrease (P
      < 0.05) in BMD on Day 21.

PMID- 9245549
TI  - Cerebrospinal fluid cytokines in patients with tuberculous meningitis.
AB  - The level of tumor necrosis factor (TNF)-alpha, soluble TNF receptors p75 (sTNFR
      75) and sTNFR-55, interferon (IFN)-gamma, and interleukin (IL)-10 and IL-12 were
      measured in 59 cerebrospinal fluid (CSF) samples from 15 patients with
      tuberculous meningitis (TBM). TBM was associated with elevated concentrations of
      TNF-alpha, sTNFR-75, sTNFR-55, IFN-gamma, and IL-10, while CSF IL-12 was
      undetectable in all TBM patients. A significant correlation between cytokines and
      CSF adenosine deaminase activity was also found. The levels of TNF-alpha did not
      decrease over time, being still detectable in the CSF 16 months after starting
      antibiotic therapy, whereas IFN-gamma along with anti-inflammatory mediators
      sTNFR-75, sTNFR-55, and IL-10 remained elevated in the CSF for 4-8 months. The
      chronic release of cytokines in the CSF compartment was related neither to the
      TBM stage nor to the clinical outcome of the disease, thus suggesting the
      presence of a continuous activity of the inflammatory process at the site of
      infection.

PMID- 9245550
TI  - Effects of sialadenitis after cellular transfer in autoimmune MRL/lpr mice.
AB  - The MRL/Mp mice bearing a lymphoproliferative gene, lpr (MRL/Mp-lpr/lpr), provide
      an appropriate model for the study of autoimmune mechanisms leading to the
      destruction of salivary and lacrimal gland tissue in Sjogren's syndrome. By 7-8
      weeks of age, progressive focal inflammatory cell infiltrates are observed in
      salivary glands. We examined the possibility of transferring this disorder into
      syngeneic, young animals. Spleen cells and infiltrating mononuclear cells (MNC)
      enzymatically eluted from salivary glands were used. The results showed that
      sialadenitis could be transferred in vivo to young MRL/lpr mice by splenic and
      salivary gland MNC. The most striking finding was observed in male recipients
      where the highest incidence of sialadenitis (5/5) was seen in the group injected
      intravenously with a small dose (1 x 10(6) of salivary gland MNC, CD8+ splenic
      cells alone were not able to transfer disease. On the other hand, CD4+ splenic
      cells induced a more severe sialadenitis compared to the control animals. The
      transfer of pooled cells from salivary glands resulted in the most severe and
      accelerating sialadenitis (P < 0.05) in female recipients compared with the
      control animals. Overall, the highest sialadenitis scores (> 0.10) were obtained
      only after transfer of CD4+ spleen cells and infiltrating salivary gland MNC.
      These findings indicate that sialadenitis in MRL/lpr mice is mediated by cellular
      mechanisms and suggest that the infiltrating MNC have the ability to accelerate
      autoimmune disease in the salivary glands.

PMID- 9245551
TI  - Bacterial DNA-induced NK cell IFN-gamma production is dependent on macrophage
      secretion of IL-12.
AB  - Bacterial DNA (bDNA) activates B cells and macrophages and can augment
      inflammatory responses by inducing release of proinflammatory cytokines. We found
      that bDNA stimulation of mouse spleen cells induced NK cell IFN-gamma production
      that was dependent upon the presence of unmethylated CpG motifs, and
      oligonucleotides with internal CpG motifs could also induce splenocytes to
      secrete IFN-gamma. The bDNA-induced IFN-gamma response was strictly macrophages
      dependent. While splenocytes from SCID mice secreted IFN-gamma in response to
      bDNA, depletion of macrophages eliminated this response. Additionally, purified
      NK cells did not respond to bDNA; however, addition of macrophages restored the
      NK cell IFN-gamma response. Coculture of NK cells with preactivated macrophages
      further increased bDNA-induced NK cell IFN-gamma production. Anti-IL-12 or IL-10
      inhibited bDNA-induced IFN-gamma response. Treatment of purified macrophages with
      bDNA resulted in IL-12 secretion accompanied by an increase in IL-12 p40 mRNA
      level. Although isolated NK cells did not make IFN-gamma in response to bDNA, NK
      cells costimulated with IL-12 gained the ability to respond to bDNA. These
      experiments show that bDNA induces macrophage IL-12 production which, in turn,
      stimulates NK cell IFN-gamma production. Macrophage-derived IL-12 renders NK
      cells responsive to bDNA permitting an even greater IFN-gamma response to bDNA.

PMID- 9245552
TI  - Selective IgG1 deficiency.
AB  - Measurement of serum IgG subclass levels in 3005 patients disclosed abnormally
      low IgG1 levels with normal levels of the other IgG subclasses and of IgM and IgA
      in 119 patients, predominantly adults. Not all patients were
      hypogammaglobulinemic due to nonrare increases of other isotypes, mostly IgM. A
      familial context of immunodeficiency was frequent, more often combined than
      selective IgG1 deficiency. A familial association with IgG2 deficiency was found
      also and IgG1 replaced IgG2 deficiency in 3 cases (and succeeded to or preceded
      more complex IgG defects in 3 cases, whereas IgG1 deficiency was consistently
      found at examinations repeated in the absence of therapy in 10 additional cases).
      Most but not all (83.2%) patients suffered infections, generally moderate,
      similar to those observed in other selective IgG subclass deficiencies (IgGSD),
      with predominantly sinorespiratory infections. Other clinical manifestations such
      as atopy, congenital cardiopathy, and autoimmune diseases were already known in
      IgGSD but the incidence of asthma was strikingly high (one-fifth of the cases).

PMID- 9245553
TI  - The presence of antibodies against HIV peptides in the sera of alloimmune mice
      and thalassemic patients is due to a polyclonal activation mechanism.
AB  - This paper analyses the HIV-1 gp120 epitope specificity and activation mechanisms
      (i.e., polyclonal versus oligoclonal) of antibodies present in the sera of
      alloimmune mice and humans. Sera from CBA mice engrafted with C57BL/6 lymphoid
      cells significantly reacted against the gp120-derived peptide as 261-270, which
      shares high homology with the membrane-proximal domain of HLA class II beta
      chains (HLA/ gp120) and against the HIV gp120 V3 loop-derived peptides DP32 (HIV
      1 MN-derived as 302-334) and C53 (HIV-1 IIIB-derived as 304-318). The same sera
      also reacted against the HIV-unrelated peptide necdin. Moreover, sera from BALB/c
      mice injected with LPS presented antibodies reacting against both HIV-related and
      -unrelated peptides, suggesting that similar mechanisms are shared in alloimmune
      and LPS-treated mice. A similar analysis was then performed on the sera of
      patients affected with beta-thalassemia major, receiving at least 10 blood
      transfusions/year. In particular, 15 of 58 (26%) sera from HIV-uninfected
      thalassemic patients showed a significantly reactivity against the HLA/gp 120
      derived peptides. Moreover, 22 of 58 (38%) sera from the same cohort showed a
      significant reactivity against DP32 peptide. This reactivity was related to a
      polyclonal activation mechanism since the DP32-reactive sera significantly bound
      a panel of HIV-unrelated peptides, as observed by testing 22 sera against necdin,
      21 against HSP65 kDa, 21 against amyloid-1, and 17 against MAGE-1 peptides.
      Moreover, a significant increase of IgG concentration was also observed in all
      thalassemic sera, when compared to healthy controls, without regard to the anti
      gp120 antibody reactivity. Taken together, these results indicate that (i)
      allogeneic stimuli may induce anti-gp120 antibodies in CBA and in 38% of
      polytransfused patients and (ii) this reactivity is related to a polyclonal
      activation mechanism but not to a heightened concentration of IgG.

PMID- 9245554
TI  - Phagocytosis of nonopsonized Cryptococcus neoformans by swine microglia involves
      CD14 receptors.
AB  - The interaction of the opportunistic fungus Cryptococcus neoformans with swine
      microglia was studied in vitro in the presence and absence of anti-CD14
      monoclonal antibodies. In the absence of anti-CD14 antibodies, 36% of microglia
      had phagocytized nonopsonized, encapsulated cryptococci after 2 hr incubation
      (effector-to-target ratio, 1:50). Preincubation of microglia with anti-CD14
      antibodies resulted in a 63% reduction of phagocytosis. These findings suggest
      that CD14 receptors facilitate uptake of nonopsonized C, neoformans by resident
      macrophages within the brain.

PMID- 9245555
TI  - Coexpression of CD40 and class II antigen HLA-DR in Graves' disease thyroid
      epithelial cells.
AB  - In Graves' disease, thyroid epithelial cells abnormally express HLA-DR Class II
      molecules in the vicinity of lymphocyte infiltrates, suggesting that lymphocyte
      proliferation is sustained by the appropriate presentation of antigenic material.
      The ability of thyroid epithelial cells to provide the necessary second signals
      has however not been documented. The expression of HLA-DR, CD40, CD40L, CD80, and
      CD28 was investigated on thyroid samples from 30 patients (Graves' disease, n =
      16; benign toxic adenoma, n = 8; multinodular goiter, n = 6). Apoptotic cells
      were searched for using the TUNEL method. CD40 appeared to be coexpressed with
      HLA-DR in Graves' disease patients samples and in two control samples also
      containing lymphoid infiltrates. Almost no apoptotic cells were found. These data
      suggest that thyroid epithelial cells from Graves' disease patients have the
      ability to successfully present autoantigens. The near absence of apoptotic cells
      in surrounding lymphoid infiltrates is in keeping with this efficient provision
      of a rescue second signal.

PMID- 9245556
TI  - Development of bone marrow eosinophilia in mice induced by Aspergillus fumigatus
      antigens.
AB  - A model of allergic bronchopulmonary aspergillosis (ABPA) developed by exposing
      mice to Aspergillus fumigatus antigen (Af) exhibits peripheral blood (PB), lung,
      and bone marrow (BM) eosinophilia. Because the BM is a site of
      eosinophilopoiesis, we have investigated the role of Af in the induction of this
      process in the BM. Groups of mice were exposed intranasally (i.n.) or
      intraperitoneally (i.p.) to Af. BM cells from mice were cultured with either Af
      or allogenic spleen cell supernatant stimulated with Af. Eosinophil counts in
      different lymphoid compartments, eosinophil peroxidase (EPO), and mRNA for
      cytokines and IgE in BM cells were studied. Results indicate that the eosinophil
      numbers were significantly elevated in PB and BM of all Af-exposed mice. Lung
      lavage eosinophils increased only in the i.n. group. Af induced EPO activity only
      in BM cultures from Af-exposed mice. The EPO activity was further enhanced by
      supernatants from spleen cells from Af-exposed mice. mRNA transcription of IL-3
      and IL-5 were measurable in BM cells of the ip exposed mice. These findings
      suggest that Af mediates eosinophil development in BM of mice and this process is
      promoted by hematopoietic factors generated within the BM and in other lymphoid
      tissue such as the spleen.

PMID- 9245557
TI  - Acute epicardial ECG parameters as quantitative predictors of infarct size at 1
      week in the baboon.
AB  - We describe an experimental baboon model that allows quantitative prediction of
      myocardial necrosis measured at 1 week from acute epicardial ECG parameters
      recorded from a high-resolution matrix of fixed epicardial electrodes. The
      electrode grid overlies a circumscribed area of ultimate necrosis, produced by
      the occlusion of a selected diagonal branch of the left anterior descending
      coronary artery (LAD). This grid allowed examination of the pattern of changes in
      ST segment elevation (ST increases) throughout their return to control levels,
      and profiled changes in the distribution of electrodes recording TQ-ST segment
      deflections. Those points more centrally located within the area of ST increases
      consistently showed greater absolute values of ST increases and remained elevated
      longer than the more peripheral electrodes. Areas of the electrode matrix
      corresponding to those electrode points showing significant ST increases (2 mV
      above control) at each recording interval through 8 hr were fitted to the area of
      necrosis underlying this electrode grid. While the maximum area of ST increases
      (maxAst) uniformly overestimated infarct size between animals on the order of
      25%, regression analysis allowed prediction of the extent of infarct from maxAst
      with an error of only 5%. Correlation of maxAst with the epicardial extent of
      infarct, total weight, and volume yielded coefficients of 0.95, 0.85, and 0.91
      respectively, while mean ST increases (ST increases) showed a poorer correlation
      with respective coefficients of 0.49, 0.55, and 0.39. MaxAst proved to be the
      single best predictor of infarct size assessed at 1 week.

PMID- 9245558
TI  - Inducible macrophage apoptosis following sepsis is mediated by cysteine protease
      activation and nitric oxide release.
AB  - Recent studies indicate that polymicrobial sepsis can markedly increase inducible
      macrophage Ao (nonnecrotic cellular suicide) and that this is associated with
      decreased M phi function. In vitro studies suggest that M phi Ao can be induced
      by IL-1 beta via interleukin-1 beta-converting enzyme (ICE, a cysteine protease),
      prostanoids, or reactive oxygen/nitrogen. However, the mechanism(s) underlying
      this process in septic M phi remains unknown. To determine this, male C3H/HeN
      mice were subjected to sepsis (cecal ligation and puncture, CLP) or sham
      operation. Twenty-four hours thereafter, M phi were isolated from the peritoneum
      (PM phi) and liver (LM phi). Macrophage monolayers were treated with LPS (10
      micrograms/ml) alone (Cont) or in the presence of iodoacetamide (Iodo, 5 mM), N
      methylmalamide (meth, 5 mM), ibuprophen (Ibu, 40 micrograms/ml), N-methyl-L
      arginine (LNMA, 0.4 mM), or superoxide dismutase (SOD, 60,000 U/ml) for 24 hr.
      The extent of Ao was determined using an enzyme-linked immunosorbent cell-death
      assay, which detects the presence of cytoplasmic oligonucleosomes measured as
      optical density. The results indicate that both PM phi and LM phi from septic
      animals exhibit increased Ao over cells from sham animals. However, only the
      nonspecific cysteine protease inhibitors (Iodo and meth) and the NO inhibitor
      LNMA blocked septic mouse M phi Ao. Furthermore, only PM phi from CLP mice
      treated with Iodo, but not LNMA or IBU, showed an improved capacity to release IL
      6. We conclude that increased M phi Ao seen during sepsis appears to be mediated
      by both ICE-like cysteine protease activation and NO release but the
      level/mechanism of action of these inhibitors differs.

PMID- 9245559
TI  - Nitric oxide inhibition simulates the enhancement of alpha 1 agonist-induced
      vasoconstriction in diabetes.
AB  - We have previously reported that endothelium-dependent, nitric oxide (NO)
      mediated vasorelaxation is impaired in diabetic mesenteric arteries. We
      hypothesized that vasoconstrictor responses should therefore be enhanced. The
      purpose of this study was to determine whether diabetic mesenteric arteries
      exhibit increased vasoconstrictor responses, and to investigate if these changes
      are receptor and/or NO mediated. Thirty age-matched male Sprague-Dawley rats were
      divided into control (C) and diabetic (D, streptozotocin: 60 mg/kg) groups and
      studied after 4 weeks. Terminal branches of ileal mesenteric arteries (300 +/- 9
      microns) were isolated, pressurized, and superfused with modified Krebs solution.
      Changes in vessel internal diameter were measured and dose-response curves (DRC)
      for each vasoactive agent were determined. Each vessel was initially constricted
      with 40 mM of KC1 to determine maximal vasoconstriction. Phenylephrine (Phe, 10(
      8)-10(-4) M) and UK14304 (10(-9)-10(-5) M) were used to determine alpha 1- and
      alpha 2-receptor responses, respectively. Similar studies were performed in the
      presence of N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), a
      competitive inhibitor of NO synthase. Maximal response (Max), area under the
      curve (AUC), and vessel sensitivity (ED50) for each DRC were calculated.
      Comparisons among groups were made using analysis of variance and Student's t
      test with Bonferroni correction. There were no differences in vasoconstrictor
      responses induced by KCl (C: 82 +/- 2% vs D: 80 +/- 1%). alpha 1-vasoconstrictor
      responses to Phe were enhanced in diabetes with significantly higher Max (96 +/-
      2% vs 83 +/- 3%), and AUC (1.92 +/- 0.09 vs 1.56 +/- 0.08), but no difference in
      ED50. The addition of L-NAME enhanced only Phe-induced vasoconstrictor response
      significantly in control rats. Thus, differences in Phe-induced vasoconstrictor
      responses between C and D were abolished in the presence of L-NAME. alpha 2
      vasodilator responses induced by UK14304 were similar between C and D and
      unaffected by L-NAME. alpha 1-, but not alpha 2-, vasoconstrictor responses are
      enhanced in streptozotocin-induced diabetic rats. These enhanced responses can be
      duplicated by treatment of control vessels with L-NAME.

PMID- 9245560
TI  - NO as an indicator of portal hemodynamics and the role of iNOS in increased NO
      production in CCl4-induced liver cirrhosis.
AB  - It is well known that nitric oxide, a vasodilator, is overproduced in liver
      cirrhosis. This study was designed to elucidate the role of nitric oxide (NO) in
      portal hemodynamics and to determine the mechanism underlying the increased serum
      NO levels in rats with liver cirrhosis induced by the oral intake of CCl4. Using
      rats, liver cirrhosis was induced by oral administration of CCl4. The serum
      levels of NO2-/NO3-(NOx) were measured, and portal hemodynamic parameters were
      evaluated with and without the administration of the NO synthase inhibitor N
      omega-nitro-L-arginine (NNA). Furthermore, Northern blot analysis was used to
      detect iNOS and cNOS mRNA, and immunohistochemical methods were used to detect
      iNOS-like immunoreactivity. In cirrhotic rats, the portal flow had increased
      significantly and the portal resistance had decreased significantly when compared
      with normal control rats. Hepatic capillary flow in the cirrhotic rats was
      similar to the control rats. NNA decreased portal flow and increased portal
      resistance in both groups, but the change was greater in the cirrhotic rats than
      in controls. The serum levels of NOx were significantly higher in cirrhotic rats
      than in normal control rats and were positively correlated with portal flow and
      negatively correlated with portal resistance. The expression of iNOS mRNA, which
      was barely detectable in control rats, had increased in all organs of the
      cirrhotic rats, whereas no significant increase in cNOS mRNA was found in any of
      the organs from cirrhotic rats. The immunohistochemical analysis was generally
      consistent with the results of the Northern blot analysis. In the control rats,
      only the bronchial epithelial cells were stained with the anti-iNOS antibody, but
      in cirrhotic rats, the bronchial cells in the lungs as well as the histiocytic
      mesenchymal cells in all organs, and the alveolar epithelial cells of the lungs,
      were stained. This study demonstrated that NO plays a significant role in portal
      hypertensive hemodynamics in CCl4-induced liver cirrhosis, and that NO is a
      useful indicator for the evaluation of portal hypertension. Furthermore, the
      increased serum levels of NO were found to be derived at least in part from the
      increased expression of iNOS mRNA in the liver, spleen, and lung.

PMID- 9245561
TI  - Serial ultrasound-guided percutaneous liver biopsy in a partial hepatectomy
      porcine model: a new technique in the study of liver regeneration.
AB  - Studies on liver regeneration are often carried out on small animal models such
      as the rat. The use of large animal models however has many advantages. Repeated
      biopsies of the liver may be carried out and the animal can thus serve as its own
      control. Sequential changes in the regenerative response to various putative
      hepatotrophic factors can therefore be studied. Ultrasound-guided percutaneous
      biopsy (USGPB) of the liver, a technique widely used in clinical practice to
      obtain liver samples, offers a means for repeated liver biopsies. This study was
      carried out to validate the use of serial USGPB of the liver as a research
      technique in the study of liver regeneration in a porcine hepatectomy model.
      MATERIAL AND METHOD: Left hepatectomy was carried out in nine Yorkshire pigs (20
      30 kg). Bromodeoxyuridine (BrdU) at 50 mg/ kg BW was administered daily for the
      first 5 days after surgery. USGPB was carried out 1 hr later using 16F biopsy
      needles in a Biopty device. Ultrasonography was carried out using an Acuson XP10
      color doppler ultrasound machine. Immunoperoxidase staining of the biopsy
      specimens was performed using mouse monoclonal antibody to BrdU. Regenerating
      cells were identified and labeling indices constructed for each day after
      hepatectomy. All animals were sacrificed at the end of the study and postmortem
      was performed. RESULTS AND CONCLUSION: USGPB was successful at every attempt and
      no animal suffered complications following the procedure. Median cumulative
      labeling indices increased rapidly after hepatectomy and the steepest rise
      occurred between the third and fourth day after surgery when it increased from
      2.25 to 3.40% before leveling off. These results are consistent with those
      obtained by other reported techniques. USGPB of the liver overcomes the need for
      repeated laparotomies to obtain biopsy samples in a large animal model and has no
      morbidity and mortality that could lead to animal wastage.

PMID- 9245562
TI  - Endogenous versus exogenous IL-10 in postoperative intraperitoneal adhesion
      formation in a murine model.
AB  - BACKGROUND: Modulation of the immune response to peritoneal injury may prevent
      postoperative adhesion formation. Exogenous interleukin-10 (IL-10) limits
      postoperative adhesion formation. The objective of the present study is to
      determine (I) the IL-10 dose most effective at adhesion prevention, (II) the
      presence of endogenous IL-10 in peritoneal fluid, and (III) the ability of an
      anti-IL-10 monoclonal antibody to modify postoperative intraperitoneal adhesion
      formation. MATERIALS AND METHODS: Within parts I, II, and III of the study 8-week
      old Swiss Webster mice were randomized to have no surgery or to undergo a
      standardized adhesion-inducing peritoneal injury. Animals were further randomized
      to different dosing schedules of IL-10 (10 ng/kg to 100 micrograms/kg; part I),
      different times of euthanasia and peritoneal lavage after surgery (part II), or
      intraperitoneal (i.p.) treatment with phosphate-buffered saline vehicle (1 ml),
      IL-10 (1 microgram/kg), or anti-IL-10 (1 microgram/kg; part III). All i.p.
      injections were given immediately after surgery and then every 24 hr for a total
      of four injections. Animals were sacrificed 7 days after surgery and adhesion
      formation was assessed. RESULTS: Maximal adhesion-limiting effects of exogenons
      IL-10 were reached at doses of 1 microgram/kg. Mean detectable endogenous IL-10
      levels in the peritoneal fluid varied from 145 to 220 pg/ml throughout the
      postoperative course. There were significant (P < 0.0005) differences in adhesion
      scores between mice treated with IL-10 (3.39; 95% CI 0.39-6.39) or PBS
      postoperatively (7.46; 95% CI 5.28-9.64), untreated surgical control animals
      (5.98; 95% CI 2.55-9.41), or anti-IL-10-treated animals (10.11; 95% CI 8.50
      11.72). CONCLUSION: Interleukin 10 is effective at reducing postoperative
      intraperitoneal adhesion formation. Low levels of endogenous IL-10 are detectable
      in peritoneal fluid throughout the postoperative course, not correlating with
      adhesion scores. Anti-IL-10, when administered daily postoperatively in
      pharmacologic doses, does not appear to significantly increase postoperative
      adhesion formation. This puts into question if endogenous IL-10 production indeed
      plays a role in nonadhesiogenic peritoneal healing.

PMID- 9245563
TI  - Mechanisms of hyperinsulinemia and hyperglucagonemia after liver transplantation.
AB  - These studies were undertaken to evaluate the mechanisms for changes in plasma
      insulin and glucagon levels observed post-liver transplantation. Two groups of
      pigs were studied: a control group (n = 8) underwent laparotomy and catheter
      placement in the carotid artery and portal and hepatic veins. Hepatic blood flow
      was measured by ultrasonic flow probes placed around the hepatic artery and
      portal vein. An experimental group (n = 8) underwent orthotopic liver
      transplantation and similar instrumentation. On Day 1 after surgery, an estimate
      of insulin and glucagon secretion and hepatic extraction was determined using
      arteriovenous difference techniques. Serum assays were performed for markers of
      hepatic and renal function. Plasma insulin levels of the transplanted pigs were
      higher in the carotid artery (4 +/- 1 microU/ml vs 7 +/- 1 microU/ml), but not in
      the hepatic vein (5 +/- 1 microU/ml vs 7 +/- 1 microU/ml) and in the portal vein
      (10 +/- 2 microU/ml vs 12 +/- 2 microU/ml). Arterial plasma C-peptide was
      significantly greater in the transplanted group (0.23 +/- 0.02 ng/ml vs 0.42 +/-
      0.03 ng/ml); however, the molar ratio of C-peptide and insulin was not different
      between the two groups (3.6 +/- 0.9 vs 3.4 +/- 0.4). Plasma glucagon levels of
      the transplanted pigs were significantly elevated in the carotid artery (111 +/-
      11 pg/ml vs 323 +/- 65 pg/ml), portal vein (221 +/- 27 pg/ml vs 495 +/- 69
      pg/ml), and hepatic vein (142 +/- 15 pg/ml vs 395 +/- 58 pg/ml). The estimate of
      pancreatic secretion of insulin (115 +/- 28 microU/kg.min) vs 71 +/- 21
      microU/kg.min) and glucagon (2.0 +/- 0.4 ng/kg.min vs 2.7 +/- 0.7 ng/kg.min) and
      the fractional hepatic extraction rate of insulin (35 +/- 8% vs 32 +/- 5%) were
      not different between the two groups. However, the hepatic fractional extraction
      rate of glucagon was significantly decreased in the transplanted group (25 +/- 5%
      vs 11 +/- 3%). Therefore, the hyperglucagonemia observed 24 hr following liver
      transplantation is partly due to reduced hepatic fractional extraction of
      glucagon while the hyperinsulinemia is mainly due to the nonhepatic clearance of
      insulin. We speculate that decreased renal function may contribute to the
      hyperinsulinemia, elevated C-peptide concentrations, and hyperglucagonemia.

PMID- 9245564
TI  - Heat shock protein 70 expression in native and heterotopically transplanted rat
      hearts.
AB  - Heat shock proteins (hsp) are intracellular proteins that are rapidly synthesized
      in response to a variety of stress factors. Recent studies in rats have shown
      that these proteins can elicit a lymphocyte response during cardiac allograft
      rejection. We studied the expression of the inducible (i) and constitutive (c)
      forms of hsp70 in rat cardiac allograft and isograft recipients to evaluate their
      utility as indicators of transplant rejection. Heterotopic transplantation of rat
      hearts was performed, using Lewis to Lewis isografts and ACI to Lewis allografts.
      Sham-operated rats were used as controls. Transplanted isograft, allograft, and
      native hearts of the transplant recipients and their livers and spleens were
      harvested at 5 days posttransplant and analyzed for hsp70 (i) and (c) expression
      by Western blots. Seven animals were studied in each group. Isografts at 3 and 60
      days and allografts at 8 days were also studied. Quantification of band densities
      was carried out by laser densitometry. Physiological function of the native
      hearts of the transplant recipients was studied using Langendorff preparations.
      High levels of hsp70 (i) were noted in the transplanted and native hearts of the
      transplant recipients but not in their livers or spleens or in the hearts of the
      sham-operated control animals. Myocardial function of the native hearts of the
      transplant recipients was not significantly different from that of the controls.
      Significantly higher levels of hsp70 (c) were present in mild and severely
      rejecting allografts compared with controls and nonrejecting isografts. In the
      rat model of heterotopic cardiac transplantation, high levels of hsp70 (i) in the
      native hearts of the allograft and isograft recipients suggest a transplant
      related, cardiac-specific stress process, not previously described. Heat shock
      protein 70 (c) expression is significantly increased during early and late
      allograft rejection and may serve as an indicator of transplant rejection.

PMID- 9245566
TI  - Candida albicans and Escherichia coli are synergistic pathogens during
      experimental microbial peritonitis.
AB  - Candida albicans has been isolated with increasing frequency during
      intraabdominal infection; yet its role as a pathogen or copathogen remains
      controversial. A recent experimental study of its effect during polymicrobial
      peritonitis indicated that it did not enhance mortality when added to an
      Escherichia coli challenge, but that study used fecal or mucin-based adjuvants
      which are known to markedly potentiate the lethality of intraperitoneal bacteria.
      Therefore, we sought to examine the hypothesis that C. albicans and E. coli are
      synergistic copathogens that act in concert to increase mortality rates in
      experimental models of polymicrobial peritonitis, irrespective of the presence of
      growth adjuvant. To test this hypothesis, we assessed the mortality rates of
      previously healthy Swiss-Webster mice (20 g) that were challenged
      intraperitoneally (i.p.) with E. coli, C. albicans, or both, in either the
      presence or the absence of hemoglobin-mucin. In the absence of hemoglobin-mucin,
      E. coli plus C. albicans resulted in 83.3% mortality (P < 0.02) compared to
      either E. coli (0%) or C. albicans (0%) alone. In the presence of hemoglobin
      mucin, the synergistic effect was not observed, lower numbers of E. coli alone
      (62.5%), C. albicans alone (75%), or both organisms together (100%, P > 0.05)
      provoked high lethality. These data demonstrate that in the absence of adjuvant,
      E. coli plus C. albicans provoked synergistic lethality. However, in the presence
      of hemoglobin-mucin the synergistic effect was no longer observed. Therefore,
      this study provides support for the contention that C. albicans is capable of
      acting as a copathogen during experimental peritonitis, but that this effect may
      be obscured by the presence of an adjuvant substance that itself markedly
      potentiates microbial growth.

PMID- 9245565
TI  - Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK
      044) in the transplanted liver.
AB  - This study was designed to investigate whether or not a novel nonselective
      endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection
      during porcine liver transplantation. The grafts were stored in chilled Euro
      Collins solution and recirculated following reflush with lactated Ringer's with
      (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular
      (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured
      in the hepatic biopsy materials obtained serially at varying time point from
      donor laparotomy to recipient closure using an electron probe X-ray
      microanalyzer. Liver function tests also were determined. The cold and warm
      ischemia times of the grafts were comparable between the two groups. The peak
      endothelin-1 T-1) concentration after recirculation was significantly higher in
      the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml).
      However, release of liver enzymes, increases in total bile acid, and
      deterioration of indocyanine green retention rate were significantly suppressed
      in the TAK group. In the control group, the intracellular Ca concentrations,
      especially in the mitochondrial fraction, were elevated markedly following
      recirculation of the hepatic arterial flow. In the TAK group, this effect was
      suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor
      antagonist TAK-044 via a rinse route may alleviate an early postreperfusion
      microcirculatory disturbance of the liver grafts without adverse effects by the
      increased ET-1 on the systemic circulation.

PMID- 9245567
TI  - Beta-adrenergic stimulation down-regulates neutrophil priming for superoxide
      generation, but not elastase release.
AB  - Platelet-activating factor (PAF) concordantly primes neutrophils (PMNs) for
      superoxide generation and elastase release. beta-Adrenergic stimulation of PMNs
      enhances cAMP-dependent protein kinase A (PKA) activity and has been shown to
      inhibit PAF-mediated NADPH-oxidase activity. PMN superoxide generation is thought
      to play a predominate microbicidal role, whereas elastase is known to mediate
      untoward PMN-endothelial interactions. We hypothesized that beta-adrenergic
      neutrophil stimulation has disparate effects on PAF-mediated PMN superoxide
      generation versus elastase release. Human PMNs were isolated using a standard
      Ficoll/Hypaque gradient. PMNs were then primed with PAF (200 nM) and activated
      with fMLP (1 microM). Subsets of PMNs were pretreated for 5 min with a beta
      agonist (10(-4) M isoprotereno) or an adenylate cyclase agonist (10(-5) M
      forskolin). Superoxide generation was determined by superoxide dismutase
      inhibitive cytochrome c reduction. Elastase activity was measured by the cleavage
      of n-methoxylsuccinyl-A-A-P-V-p-nitroanilide. Pretreatment with isoproterenol and
      forskolin yielded superoxide generation of 3.2 +/- 0.6 and 3.1 +/- 1.2 nmole/2.5
      x 10(5) PMN/min compared to 9.0 +/- 0.6 nmole/2.5 x 10(5) PMN/min for PAF/fMLP
      alone, whereas isoproterenol and forskolin did not significantly affect PAF
      mediated neutrophil elastase release, 22.4 +/- 5.3 and 24.0 +/- 3.6%,
      respectively, compared to 39.4 +/- 9.1% for PAF/fMLP alone. Disparate PMN signal
      transduction for superoxide generation versus elastase release may explain the
      SICU clinical paradox, in which patients are both susceptible to infection and
      vulnerable to PMN-mediated multiple organ failure.

PMID- 9245568
TI  - Epidermal growth factor receptor expression following small bowel resection.
AB  - BACKGROUND: Adaptation following massive small bowel resection (SBR) is an
      important compensatory response. While epidermal growth factor (EGF) has been
      shown to augment this response, the mechanism and role of EGF and its intestinal
      receptor (EGF-R) during adaptation are not known. The purpose of this study was
      to determine the effect of massive SBR and adaptation on intestinal expression of
      EGF-R. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent either a 75% mid
      SBR with primary reanastomosis or sham operation (bowel transection with
      reanastomosis). Ileal mucosa was harvested from animals of each group at 6 and 12
      hr, 1, 3, and 5 days, and 1, 2, and 4 weeks after operation. Expression of EGF-R
      protein was studied by Western blotting. Expression of EGF-R mRNA was determined
      by quantitative reverse-transcriptase polymerase chain reactions normalized to
      beta-actin. RESULTS: When compared with sham, SBR resulted in a modest (32%)
      increase in the expression of EGF-R mRNA at 1 week (P < 0.003). A twofold greater
      expression of EGF-R protein corresponded to this time point. While not
      statistically significant, expression of EGF-R mRNA was slightly greater after
      SBR at every other time point measured. CONCLUSION: Following massive SBR,
      expression of both EGF-R mRNA and protein is slightly increased in the ileum with
      a more pronounced increase in protein. These findings, which have not previously
      been reported, suggest that changes in EGF-R signaling may not play a major role
      during the initiation and or progression of intestinal adaptation following
      massive SBR.

PMID- 9245569
TI  - The regulation of p42/p44 mitogen-activated protein kinases in the injured rat
      carotid artery.
AB  - Arterial smooth muscle cell (SMC) proliferation is an important factor in the
      development of atherosclerotic plaques and restenotic lesions following arterial
      reconstruction. Basic fibroblast growth factor (bFGF), platelet-derived growth
      factor (PDGF), and thrombin are known to induce SMC proliferation and migration
      in vitro and in vivo. In cultured cells the proliferative responses to these
      mitogens depend on the activation of the p42/p44 mitogen-activated protein
      kinases (MAPKs), whereas the role of these kinases in vivo has yet to be
      established. We tested whether MAPK activity is induced following vessel injury
      and whether activity is dependent on the release of bFGF, PDGF, and thrombin.
      Following balloon injury of the left carotid of male Sprague-Dawley rats,
      arteries were removed and analyzed with respect to MAPK activity, BrdU-labeled
      nuclei, and/or luminal, medial, and intimal areas. MAPK activity is induced in
      the rat carotid artery following balloon-catheter injury with a maximum
      activation at 30 min with a return to just above baseline at 11 hr after injury.
      Intravenous administration of heparin or neutralizing antibodies to bFGF or PDGF
      prior to injury reduced SMC proliferation and neointimal lesional formation but
      did not affect the early induction of MAPK activity. Administration of a tissue
      factor inhibitor or thrombin inhibitor also did not affect MAPK activity,
      although it impaired the initiation of the coagulation cascade. IN CONCLUSION:
      (1) MAPK is activated in a time-dependent manner in response to injury; (2) the
      antiproliferative effect of heparin in vivo is not mediated through the
      inhibition of MAPK activity induced 30 min after injury; (3) the activation of
      MAPK after 30 min is not dependent on PDGF, bFGF, or thrombin following vessel
      injury in the rat.

PMID- 9245571
TI  - Neuroendocrine-bacterial interactions in a neurotoxin-induced model of trauma.
AB  - BACKGROUND: The destruction of noradrenergic nerve cell innervation and resultant
      release of norepinephrine into the systemic circulation accompany severe tissue
      trauma. To examine whether destruction of noradrenergic neurons may directly
      influence the growth of indigenous bacteria in vivo, the selective noradrenergic
      neurotoxic agent 6-hydroxydopamine (6-OHDA) was employed in a murine model of
      trauma-induced norepinephrine release. MATERIALS AND METHODS: Following 6-OHDA
      administration, the cecums of 6- to 8-week-old male CF-1 mice were excised and
      examined for total bacterial counts and identification of bacterial species
      present in both the luminal space and intestinal wall. Lipopolysaccharide levels
      were also measured. RESULTS: An increase of 3-5 logs in the total gram-negative
      population, most notably Escherichia coli, compared to controls on a per gram
      equivalent basis was observed at 1 day post-6-OHDA. Neurotoxin-induced
      alterations in cecal flora were completely inhibited by the prior administration
      of the catecholamine uptake blocker desipramine hydrochloride, indicating the
      specificity of the effect being due to the released norepinephrine. Within 14
      days following chemical sympathectomy, during which regeneration of noradrenergic
      neurons occurs, the cecal flora returned to the distribution observed in
      controls. Levels of lipopolysaccharide were not increased in either the luminal
      contents or cecal tissue at any of the time points. CONCLUSIONS: These results
      suggest that the destruction of noradrenergic neurons during trauma and
      consequent release of norepinephrine into the systemic circulation may influence
      the in vivo growth of the indigenous bacterial population within the
      gastrointestinal system.

PMID- 9245570
TI  - Sulfo-Lewis(x) diminishes neutrophil infiltration and free radicals with minimal
      effect on serum cytokines after liver ischemia and reperfusion.
AB  - BACKGROUND: Cell adhesion plays a central role in the pathogenesis of neutrophil
      induced hepatic injury after ischemia and reperfusion. Sialyl Lewis(x) binds to
      selectins mediating neutrophil adherence to endothelium, thereby facilitating
      subsequent migration and tissue damage. AIM: We studied the effect of a novel
      sulfo-derivative of sialyl Lewis(x), GM-1998, on the liver inflammatory response
      after ischemia and reperfusion. Specifically, we evaluated its impact on three
      key inflammatory mediators: neutrophil migration, free radicals, and serum
      cytokines. MATERIAL AND METHODS: Rats were subjected to total hepatic ischemia
      for 90 min using an extracorporeal portosystemic shunt to avoid splanchnic
      congestion. GM-1998 was given at a total dose of 20 mg/kg both prior to and after
      reperfusion. Liver function tests, liver tissue free radicals, and
      myeloperoxidase (MPO), serum cytokines (IL-1, TNF-alpha), and liver histology
      were analyzed 4 hr after reperfusion. Additionally, survival was followed for up
      to 7 days. RESULTS: Seven-day survival significantly increased from 20% in the
      control group to 65% in the sulfo-Lewis(x) treated group. Liver function tests
      and histological damage scores were improved in comparison to controls. We
      observed significant downregulation of free radicals and neutrophil migration.
      This compound did not significantly affect serum cytokine levels. CONCLUSIONS: GM
      1998 showed a protective effect in an in vivo model of severe liver ischemia and
      reperfusion by decreasing tissue free radical levels and selectin-mediated
      neutrophil migration. This protective effect was also reflected in improved liver
      function tests and histological response leading to better survival. We confirmed
      the beneficial effect of neutrophil blockade as a key target to prevent damage
      after the reperfusion phenomenon by using a glycomimetic sulfo-Lewis(x).

PMID- 9245572
TI  - A symmetrical theory of DNA sequences and its applications.
AB  - A unified symmetrical theory of DNA sequences has been established based on the
      basic symmetry of the DNA bases. It is shown that the symmetry of DNA sequences
      is inherently related to that of a cube and its inscribed regular tetrahedron. A
      DNA group is defined as a particular alternating group of order 4, in which the
      permuted objects are four bases. The symmetry of DNA sequences is described by
      the DNA group which is isomorphic to the tetrahedral group. The matrix
      representation for the DNA group has been obtained, and used to establish the
      relationships between the transforms of bases and the rotations of the
      tetrahedron. It is found that any DNA sequence can be uniquely described by three
      independent distributions, i.e., the distributions of the bases of
      purine/pyrimidine, of amino group/keto group and of strong/weak hydrogen bonds
      along the sequence. The three distributions are invariant in some sense under the
      transforms of the DNA group, indicating that the three distributions are inherent
      for the sequence. The mathematical format of the theory lays a foundation for
      further development. The applications of the theory to analyse some DNA sequences
      are presented.

PMID- 9245576
TI  - On the dynamics of synaptic vesicles: effects on the rate of neurotransmitter
      release.
AB  - Release of transmitter substances during synaptic communication in a biological
      process of great importance, and it is worthwhile to ascertain the basic
      molecular events underlying this process. We present a minimal model of synaptic
      vesicle (SV) dynamics, with which most of the major experimentally observed
      features of evoked neurotransmitter release can be reproduced. The effect of
      different parameters on the time course of evoked release as well as the effect
      of repetitive stimulation on this model system has been examined.

PMID- 9245578
TI  - Multilocus evolutionarily stable strategy models: additive effects.
AB  - A common reservation about Evolutionarily Stable Strategy analyses is that they
      fail to account explicitly for Mendelian genetics, and therefore may produce
      biologically unfeasible predictions. This note shows that Evolutionarily Stable
      Strategy and multilocus genetic analyses agree for one simple model of frequency
      dependent selection under the assumption that the effects of alleles and loci are
      completely additive. A numeric example illustrated the concepts and results
      involved.

PMID- 9245577
TI  - Model of milk protein synthesis. A mechanistic model of milk protein synthesis in
      the lactating bovine mammary gland.
AB  - A model of amino acid (AA) uptake and metabolism by the mammary gland (udder) of
      a high producing dairy cow in mid-lactation is presented. Two cell types, milk
      secreting alveolar epithelial cells, and constitutive stromal cells are
      represented separately. Solution of the model at steady state, with appropriate
      assumptions, allows calculation of amino acid (AA) pool sizes in tissue bound AA
      and milk protein bound AA, and concentrations of intracellular free AA.
      Bidirectional flux rates of amino acids between each of these pools is also
      estimated. The flow of two amino acids, phenylalanine (Phe) and tyrosine (Tyr),
      is described using uptake kinetics of the L-system AA transporter. Model results
      suggest that AA uptake capacity of the alveolar cells, and the amount/activity of
      protein translation components limit the rate of milk protein synthesis in the
      high-producing dairy cow. A considerable amount of experimental work is necessary
      to provide data, if a comprehensive quantitative understanding of milk protein
      synthesis is to be achieved.

PMID- 9245580
TI  - On the evolution of density dependent dispersal in a spatially structured
      population model.
AB  - A simple metapopulation lattice model of two competing phenotypes is presented,
      where one phenotype reacts more sensitively to overcrowding by migrating to
      neighbouring local habitats. The sensitivity is formulated by means of a
      threshold density of the subpopulations, above which dispersal is triggered off.
      If this threshold density is not very far from the local carrying capacity, an
      increased mobility provides benefits on the metapopulation level. At a
      surprisingly small difference between migrational triggering thresholds, the
      phenotype of larger mobility (or lower threshold) squeezes out the less mobile
      one from the whole system in a wide parameter range. Evolutionary considerations
      give an optimal threshold level for our model metapopulation.

PMID- 9245581
TI  - Memory models for the electrical properties of local cardiac systems.
AB  - A series of related new models for the local dynamics of cardiac tissue is
      introduced. The models are based on a simple memory-like quantity that is used to
      determine the relationship among the durations and amplitudes of the stimulated
      action potentials. The first of these models produces period-doubling and chaos,
      consistent with constant pacing experiments, when standard restitution dynamics
      would predict stability of the primary 1:1 pattern. Analysis of the associated
      one-dimensional map suggests how various physiological parameters affect the
      period-doubling sequence. Many of these relationships have been observed in
      experiments. The remaining models extend the formalism of the first to account
      for the Hopf bifurcation of 2:2 patterns observed in experiments. One of these
      models reproduces the bifurcation sequence, 1:1, 2:2, Hopf bifurcation of 2:2,
      2:2 and 2:1 seen in experiments as the pacing interval is decreased. The models
      clarify the dynamics involved in determining the amplitudes and durations of
      successive action potentials. Results from these models together with comparison
      with the experiment strongly suggest that quantities with time constants of the
      order of 50 and 400 ms exist and affect action potential formation in heart
      tissue.

PMID- 9245582
TI  - Multifactorial comparative study of spatial point pattern analysis methods.
AB  - A way of studying cooperative behaviour of biological entities (proteins, cells,
      etc.) is by using topographical analysis: the quantification of the spatial
      patterns formed by the entities considered as points. Five methods of
      topographical analysis were compared in terms of discriminant power, stability of
      parameters, methodological bias and algorithms. We tested five methods (nearest
      neighbour distribution, radial distribution, Voronoi paving, quadrat count,
      minimal spanning tree graph) which generated nine parameters on four simulated
      models (random point process, hardcore model and two cluster models) and on
      experimental cellular models. The method which offers the best discrimination
      power and stability seems to be the minimal spanning tree graph edge length
      distribution.

PMID- 9245584
TI  - HMG1 protein inhibits the translesion synthesis of the major DNA cisplatin adduct
      by cell extracts.
AB  - When situated in a fork-like synthetic DNA replication substrate, the 1,2
      intrastrand crosslink at the d(GpG) site, the most frequent adduct formed in the
      reaction between DNA and the anticancer drug cisplatin (cis
      diamminedichloroplatinum (II)), is efficiently bypassed by eukaryotic cell
      extracts. We show here that the rat high-mobility-group protein 1 (HMG1) binds
      preferentially to the platinated fork-like synthetic DNA and inhibits the
      translesion synthesis. The same protein, but without the acidic tail, inhibits
      also the translesion synthesis. These results suggest that HMG proteins might
      contribute to the sensitivity of cells to cisplatin by directly affecting DNA
      replication.

PMID- 9245585
TI  - Growth rate-optimised tRNA abundance and codon usage.
AB  - The abundance of different tRNAs in Escherichia coli at different growth rates
      correlates strongly with the usage of the corresponding cognate codons. On the
      assumption that the investment in the translation system is optimised to provide
      a maximal growth rate, the relationship between tRNA levels and codon usage can
      be predicted. When the complications due to different degeneracies and different
      association rate constants for the different tRNA-codon combinations are
      accounted for, recent data from the literature indicate that the predicted
      relations hold up very well: the tRNA levels correlate with codon frequencies in
      a way that would support a maximal growth rate. The relations can also be used to
      predict the association rate constant between an A-site codon and the cognate
      ternary complex. In the cases where they can be compared, the results agree
      reasonably well with experimental results from the literature.

PMID- 9245587
TI  - DNA sequence encodes information for nucleosome array formation.
AB  - We have examined the effects of base sequence on nucleosome array formation using
      randomly selected chicken genomic DNA sequences. DNA clones were assembled into
      chromatin under identical conditions using a defined in vitro system capable of
      generating physiologically spaced nucleosomes on some sequences. The nucleosome
      arrangements in native chromatin on the selected sequences were also examined in
      liver nuclei. Variations in nucleosome ladders were found among the different
      sequences that were similar in vitro and in nuclei. Differences in both the
      degree of regularity of nucleosome arrays and in the value of the nucleosome
      repeat length were observed. Analysis of an approximately 100 kilobase-pair
      contiguous region using cosmid clones suggested that well-ordered regions of
      chromatin, generally less than two kilobase-pairs in extent, alternate with less
      ordered regions. This mosaic arrangement for chromatin organization appears to be
      largely a consequence of information encoded in the DNA base sequence. Nucleosome
      ordering with a 210 base-pair periodicity in a highly ordered ten-nucleosome
      array appeared to result from linker histone-dependent alignment with respect to
      each of two positioned nucleosomes, approximately 1000 base-pairs apart.

PMID- 9245586
TI  - Expression of the dystrophin-related protein 2 (Drp2) transcript in the mouse.
AB  - We have recently characterised a new member of the dystrophin gene family, DRP2,
      and its murine counterpart, Drp2, which encode dystrophin-related protein 2
      (DRP2). DRP2 is predicted to resemble certain short C-terminal isoforms of
      dystrophin and dystrophin-related protein 1 (DRP1 or utrophin). We describe here
      a comprehensive survey of Drp2 expression in the mouse by RT-PCR, and compare the
      expression profile of Drp2 with that of the related genes Dmd, Drp1 and Dag1 that
      encode all the known isoforms of dystrophin, DRP1/utrophin and a component of the
      dystrophin-associated protein complex, dystroglycan, respectively. Drp2 was shown
      to be expressed throughout the central nervous system (CNS) and in several
      peripheral tissues including the eye, kidney, teeth, oesophagus, colon,
      epididymis and ovary. The expression of Drp2 in the CNS was then further defined
      by in situ hybridization. Overall, the pattern of Drp2 expression corresponds to
      a subset of the brain regions known to express Dag1, and shows substantial
      overlap with regions that express various isoforms of dystrophin (particularly in
      the cerebral cortex, hippocampus and cerebellum). These data define the
      distribution of Drp2 expression in the mouse, and raise the possibility that in
      the CNS it may be an important component in neuronal dystrophin-associated
      complexes.

PMID- 9245588
TI  - Molecular properties of complexes formed between the prion protein and synthetic
      peptides.
AB  - Complexes of the Syrian hamster cellular prion protein (PrPC) and synthetic
      Syrian hamster PrP peptides were found to mimic many of the characteristics of
      the scrapie PrP isoform (PrPSc). Either PrPC expressed in chinese hamster ovary
      (CHO) cells or a C-terminal fragment of 142 residues of recombinant PrP protein
      (rPrP) produced in Escherichia coli was mixed with an excess of a synthetic 56
      amino acid peptide, denoted PrP(90-145). Complex formation required PrPC or rPrP
      to be destabilized by guanidine hydrochloride (GdnHCl) or urea and PrP(90-145) to
      be in a coil conformation; it was enhanced by an acidic environment, salt and
      detergent. If PrP(90-145) was in a beta-sheet conformation, then no complexes
      were formed. While complex formation was rapid, acquisition of protease
      resistance was a slow process. Amorphous aggregates with a PrPC/PrP(90-145) ratio
      of 1:1 were formed in phosphate buffer, whereas fibrils with a diameter of
      approximately 10 nm and a PrPC/PrP(90-145) ratio of 1:5 were formed in Tris
      buffer. The complexes were stable only in the presence of excess peptide in
      either the coil or beta-sheet conformation; they dissociated rapidly after
      centrifugation and resuspension in buffer without peptide. Neither a peptide
      having a similar hydrophobicity profile/charge distribution to PrP(90-145) nor a
      scrambled version, denoted hPrP(90-145) and sPrP(90-145), respectively, were able
      to induce complex formation. Although hPrP(90-145) could stabilize the
      PrPC/PrP(90-145) complexes, sPrP(90-145) could not. Studies of PrPC/peptide
      complexes may provide insights into how PrPC interacts with PrPSc during the
      formation of a nascent PrPSc molecule and into the process by which PrPC is
      converted into PrPSc.

PMID- 9245589
TI  - Sequence of the human immunoglobulin diversity (D) segment locus: a systematic
      analysis provides no evidence for the use of DIR segments, inverted D segments,
      "minor" D segments or D-D recombination.
AB  - We have determined the complete nucleotide sequence of the human immunoglobulin D
      segment locus on chromosome 14q32.3 and identified a total of 27 D segments, of
      which nine are new. Comparison with a database of rearranged heavy chain
      sequences indicates that the human antibody repertoire is created by VDJ
      recombination involving 25 of these 27 D segments, extensive processing at the V
      D and D-J junctions and use of multiple reading frames. We could find no evidence
      for the proposed use of DIR segments, inverted D segments, "minor" D segments or
      D-D recombination. Conventional VDJ recombination, which obeys the 12/23 rule, is
      therefore sufficient to explain the wealth of lengths and sequences for the third
      hypervariable loop of human heavy chains.

PMID- 9245590
TI  - Conformation-invariant structures of the alpha1beta1 human hemoglobin dimer.
AB  - Analysis of the conformational differences between the oxy and deoxy forms of
      hemoglobin is complicated by shifting coordinate systems and correlated motions
      between different parts of the molecule. Methods independent of any frame of
      reference were used to study the differences in structure between the oxy and
      deoxy forms of the human hemoglobin alphabeta dimer. Differences between the
      deoxy and oxy dimer structures can be characterized as rearrangements of 15
      substructures persisting between the two conformations. Such substructures are of
      two kinds, either rigid domains or tertiary substructures. Rigid domains are
      groups of residues for which all inter-residue distances are conformationally
      invariant. Residues belonging to a rigid domain do not have to be spatially
      contiguous nor must they have consecutive sequence numbers. The largest such
      substructure is a rigid core that spans both the alpha and beta monomers and
      includes 44% of the dimer. Other rigid domains exist within the heme pockets. An
      alternative but closely related view of the molecule is based on tertiary
      substructures. Unlike a rigid domain, a tertiary substructure must have
      consecutively numbered residues and the residue that ends one tertiary
      substructure begins the next. The decomposition of the dimer into tertiary
      substructures represents the dimer as a framework of connected stiff structural
      elements. Viewed as a set of tertiary substructures, the hemoglobin dimer has the
      same three principal functional elements: the dimer core and the alpha and beta
      heme pockets, with the heme pockets held to the dimer core by CD and FG corners.
      The tertiary substructures that comprise the dimer core include 51% of the
      molecule. When ligands bind at the hemes, the FG corners communicate structural
      changes in the hemes to the dimer cores, which may mediate heme-heme
      cooperativity.

PMID- 9245591
TI  - Bioincorporation of telluromethionine into proteins: a promising new approach for
      X-ray structure analysis of proteins.
AB  - A simple and efficient method for the specific and quantitative replacement of
      the naturally occurring amino acid methionine by its isosteric analogue
      telluromethionine in the expression of recombinant proteins has been developed.
      The method requires a controlable and competitive expression system like the
      bacteriophage T7 polymerase/promoter in a methionine-auxotrophic host. Using
      methionine-auxotrophic Escherichia coli strains, incorporation of
      telluromethionine at high yields has been achieved for human recombinant annexin
      V, human mitochondrial transamidase, Arabidopsis glutathione-S-transferase and
      the N-terminal domain of Salmonella tailspike adhesion protein as confirmed by
      amino acid, mass-spectrometric and X-ray analyses. Expressed and purified
      telluromethionine-proteins and native proteins were found to crystallise
      isomorphously. In terms of efficient bio-expression, isomorphism of crystals and
      relative abundance of methionine residues, the production of telluromethionine
      proteins as heavy-atom derivatives offers a valid and general approach in X-ray
      analysis by the method of multiple isomorphous replacement.

PMID- 9245592
TI  - Molecular cloning and expression of the Caenorhabditis elegans klp-3, an ortholog
      of C terminus motor kinesins Kar3 and ncd.
AB  - Common to all eukaryotes, kinesins are cytoskeletal motor proteins that mediate
      intracellular transport on microtubule tracks, using ATP hydrolysis. A
      Caenorhabditis elegans cDNA clone corresponding to the klp-3 gene, encoding a
      novel kinesin, was isolated, and mapped on LGII. Northern blot analysis using the
      klp-3 cDNA probe reveals a 1.9 kb mRNA that is transcribed at a low level during
      development. Temporal and spatial expression of the klp-3::lacZ fusion gene is
      limited to the marginal cells in the pharynx, and a group of muscle cells in the
      posterior gut region. The nucleotide sequence of klp-3 has been deduced from the
      cDNA and nematode genome sequencing consortium data. Conceptual translation of
      the klp-3 gene reveals a kinesin-like protein with its conserved motor domain
      containing the ATP binding and microtubule binding sites located in the C
      terminus. KLP-3 shares extensive homology with the yeast Kar3 and Drosophila ncd
      kinesins, which have previously been shown to mediate chromosomal movement and
      segregation during meiosis and mitosis. Overexpression of the klp-3 gene
      partially rescues the lethal phenotype of the maternal lethal him-14 ts(it44)
      mutants at non-permissive temperatures, and reduces the incidence of males caused
      by non-disjunction of the X-chromosome. Similarly, expression of a klp-3
      antisense RNA, under the control of a heat shock promoter, causes embryonic
      arrest, dead eggs and polyploid cells in transgenic lines, suggesting a critical
      role for the klp-3 function in chromosome segregation. Further analysis of the
      klp-3 gene in C. elegans may elucidate diverse functions of the C terminus
      mitotic motor proteins during development.

PMID- 9245593
TI  - An exceptionally stable helix from the ribosomal protein L9: implications for
      protein folding and stability.
AB  - The ribosomal protein L9 has an unusual structure comprising two compact globular
      domains connected by a 34 residue alpha-helix. The middle 17 residues of the
      helix are exposed to solvent while the first seven pack against and form part of
      the N-terminal domain, and the last ten form part of the C-terminal domain. Here
      we report results which show that a peptide corresponding to the central helix of
      L9 is monomeric in aqueous solution and >85% helical at 1 degrees C and 68(+/-7)%
      helical at 25 degrees C. This is considerably more helical than any other protein
      fragment studied to date. Another peptide corresponding to the middle 17 residues
      of the helix is monomeric and is 41(+/-4)% helical at 1 degrees C. Because the
      central helix has high intrinsic stability the globular N and C-terminal domains
      will likely be stabilized by their interactions with the helix. Therefore, the
      stability of the two terminal domains should not be completely independent
      because both domains gain stability from a shared structural element, the central
      helix. Also, the ability of the central helix to form native-like structure in
      isolation highlights a potential role for the helix in the early stages of the
      folding process.

PMID- 9245594
TI  - Determinants for Escherichia coli RNA polymerase assembly within the beta
      subunit.
AB  - We used binding assays and other approaches to identify fragments of the
      Escherichia coli RNAP beta subunit involved in the obligatory interaction with
      the alpha subunit to form the stable assembly intermediate alpha2beta as well as
      in the interaction to recruit the beta' subunit into the alpha2beta sub-assembly.
      We show that two regions of evolutionarily conserved sequence near the C terminus
      of beta (conserved regions H and I) are central to the assembly of RNAP and
      likely make subunit-subunit contacts with both alpha and beta'.

PMID- 9245595
TI  - Effect of DNA topology on Holliday junction resolution by Escherichia coli RuvC
      and bacteriophage T7 endonuclease I.
AB  - Holliday junctions are key intermediates in homologous genetic recombination.
      Their resolution requires specialised nucleases that nick pairs of strands at the
      junction point, leading to the separation of mature recombinants. Resolution
      occurs in either of two orientations, according to which DNA strands are cut. We
      show that DNA topology can determine the efficiency and outcome of a
      recombination reaction. Using two Holliday junction resolvases, Escherichia coli
      RuvC protein and T7 endonuclease I, we observed that supercoiled figure-8 DNA
      molecules containing Holliday junctions were resolved with a specific orientation
      bias, and that this bias was reversed by the presence of a topological tether
      (catenation). In contrast, when all topological constraints were removed by
      restriction digestion, the recombination intermediates were resolved equally in
      the two orientations. These results show that topological constraints affecting
      Holliday junction structure influence the orientation of resolution by cellular
      resolvases.

PMID- 9245596
TI  - A novel method to develop highly specific models for regulatory units detects a
      new LTR in GenBank which contains a functional promoter.
AB  - Functional promoters are composed of individual modules (e.g. transcription
      factor binding sites, secondary structure elements, repeats) arranged in distinct
      patterns. Recognition of such patterns is essential for identification of
      promoters in non-coding sequences. However, this is difficult due to the absence
      of overall sequence similarity in promoters even if they are regulated in a
      similar way. We implemented simple formal representations of general features of
      regulatory regions into an algorithm capable of developing complex models
      reflecting both the element composition and the functional organization of
      individual elements (ModelGenerator). Though ModelGenerator requires a very
      simple initial model (e.g. two modules and their relative order) it will generate
      a much more sophisticated model by analysis of the training set of at least ten
      sequences. We show ModelGenerator to successfully model different retroviral long
      terminal repeat (LTR) classes (Lentivirus as well as avian and mammalian C-type)
      which contain functional promoters. Database searches with the program
      ModelInspector demonstrated the high specificity of these models and no apparent
      false negatives were detected. We also verified one match from GenBank to the
      mammalian C-type LTR model experimentally and showed this sequence to contain an
      active promoter. Thus, the concept of modular organization of functional
      regulatory DNA regions (e.g. promoters) could be successfully implemented into a
      set of computer tools which might be flexible and specific enough to be suitable
      for prospective analysis of new genomic DNA sequences.

PMID- 9245597
TI  - Tissue-specific expression and alpha-actinin binding properties of the Z-disc
      titin: implications for the nature of vertebrate Z-discs.
AB  - Titins are giant filamentous proteins which connect Z-discs and M-lines in the
      sarcomeres of vertebrate striated muscles. Comparison of the N-terminal region of
      titin (Z-disc region) from different skeletal and cardiac muscles reveals a 900
      residue segment which is expressed in different length variants, dependent on
      tissue type. When searching for ligands of this differentially expressed domain
      by a yeast-two hybrid approach, we detected binding to alpha-actinin. The
      isolated alpha-actinin cDNAs were derived from the C-terminal region of the alpha
      actinin isoform (alpha-actinin-2) encoded by the ACTN2 gene. Therefore, the two
      antiparallel subunits of an alpha-actinin-2 homodimer will attach to actin at
      their respective C termini, whereas they will bind to the Z-disc titin at their N
      termini. This may thus explain how alpha-actinins can cross-link antiparallel
      titin and thin filaments from opposing sarcomeres. The alpha-actinin-2 binding
      site of the Z-disc titin is located within a sequence of 45-residue repeats,
      referred to as Z-repeat region. Both the N-terminal and C-terminal Z-repeats have
      alpha-actinin binding properties and are expressed in all striated muscles. By
      contrast, the more central Z-repeats are expressed in slow and fast skeletal
      muscles, as well as embryonic and adult cardiac muscles, in different copy
      numbers. Such alternative splicing of the Z-disc titin appears to be important
      for the tissue and fibre type diversity of the Z-disc lattice.

PMID- 9245598
TI  - Alanine-scanning mutagenesis of Bacillus subtilis trp RNA-binding attenuation
      protein (TRAP) reveals residues involved in tryptophan binding and RNA binding.
AB  - In Bacillus subtilis, expression of the trp genes is negatively regulated by an
      RNA binding protein called TRAP (trp RNA-binding Attenuation Protein), which is
      activated to bind RNA by binding l-tryptophan. TRAP contains 11 identical
      subunits assembled in a symmetric ring. We have used alanine-scanning mutagenesis
      to analyze the functions of surface amino acid residues of TRAP. The in vivo
      regulatory activity of each mutant TRAP was analyzed in a B. subtilis reporter
      strain containing a trpE'-'lacZ fusion. Mutant TRAP proteins with defective in
      vivo regulatory activities were characterized in vitro by measuring their
      tryptophan binding and RNA binding activities. Most of the mutant proteins with
      altered tryptophan binding, either affinity or cooperativity, contained
      substituted residues located on two loops formed by residues 25 to 33 and
      residues 49 to 52, as well as on the beta-strand and beta-turn contiguous with
      these loops. Substitution of three residues (Lys37, Lys56 and Arg58) with alanine
      resulted in significant decreases in the RNA binding activity of TRAP without
      altering tryptophan binding. Structural analysis shows that these three residues
      are directly aligned on the outer edge of TRAP. Further mutagenic analysis of
      these three residues revealed that only lysine or arginine residues at positions
      37 or 58 allow proper TRAP function, whereas at position 56, only lysine is
      functional. Residue Asn20 is the only other residue in TRAP that is located on
      the line formed by residues 37, 56 and 58, and virtually any amino acid residue
      is functional at position 20. We propose that RNA wraps around TRAP by
      interacting with residues Lys37, Lys56 and Arg58.

PMID- 9245599
TI  - Crystals by design: a strategy for crystallization of a ribozyme derived from the
      Tetrahymena group I intron.
AB  - Recently, the 2.8 A crystal structure of one domain of the self-splicing
      Tetrahymena group I intron was reported. Although it revealed much about RNA
      tertiary interactions, it contained only half of the active site. We have now
      designed a series of larger molecules that contain about 70% of the intron and
      all of the catalytic core. These RNAs were efficient in cleavage of a substrate
      RNA, consisting of the approximately 100 nucleotides from the 5' end of the
      intron, at a site corresponding to the 5' splice site. A sparse matrix was
      designed specifically for large RNAs and used to screen for preliminary
      crystallization conditions. Of the six RNAs initially tested, five were
      crystallized in this initial trial. Two of these crystals were further examined.
      The first diffracted X-rays to only approximately 16 A resolution, even when the
      crystal were very large. The second diffracted as high as 3.5 A, but the crystals
      were twinned and therefore unusable for structural studies. Site-specific
      mutagenesis was performed on the latter RNA to disrupt interactions that might
      have been responsible for the twinning. One of these mutant RNAs produced large,
      single, diffraction-quality crystals. The crystals belong to the tetragonal space
      group P42212 and have large unit cell dimensions, a=b=178 A and c=199 A. Thus, by
      variation of both sequence elements and crystallization conditions, crystals of a
      247 nucleotide catalytic RNA were obtained.

PMID- 9245601
TI  - Tertiary structural changes and iron release from human serum transferrin.
AB  - Iron release from human serum transferrin was investigated by comparison of the
      extent of bound iron, measured by charge transfer absorption band intensity (465
      nm), with changes observed by small-angle solution X-ray scattering (SAXS) for a
      series of equilibrated samples between pH 5.69 and 7.77. The phosphate buffers
      used in this study promote iron release at relatively high pH values, with an
      empirical pK of 6.9 for the convolved release from the two sites. The spectral
      data reveal that the N-lobe release is nearly complete by pH 7.0, while the C
      lobe remains primarily metal-laden. Conversely, the radius of gyration, Rg,
      determined from the SAXS data remains constant between pH 7.77 and 7.05, and the
      evolution of Rg between its value observed for the diferric protein at pH 7.77
      (31.2+/-0.2 A) and that of the apo protein at pH 5.69 (33.9+/-0.4 A) exhibits an
      empirical pK of 6.6. While Rg is effectively constant in the pH range associated
      with iron release from the N-lobe, the radius of gyration of cross-section, Rc,
      increases from 16.9+/-0.2 A to 17.6+/-0.2 A. Model simulations suggest that two
      different rotations of the NII domain relative to the NI domain about a hinge
      deep in the iron-binding cleft of the N-lobe, one parallel with and one
      perpendicular to the plane of the iron-binding site, can be significantly
      advanced relative to their holo protein positions while yielding constant Rg and
      increased Rc values consistent with the scattering data. Rotation of the CII
      domain parallel with the C-lobe iron-binding site plane can partially account for
      the increased Rg values measured at low pH; however, no reasonable combined
      repositioning of the NII and CII domains yields the experimentally observed
      increase in Rg.

PMID- 9245600
TI  - The three-dimensional structures of two complexes between recombinant MS2 capsids
      and RNA operator fragments reveal sequence-specific protein-RNA interactions.
AB  - Crystal structures of two complexes between recombinant MS2 capsids and RNA
      operator fragments have been determined at 2.7 A resolution. The coat protein of
      the RNA bacteriophage MS2 is bifunctional; it forms the icosahedral virus shell
      to protect the viral nucleic acid and it acts as a translational repressor by
      binding with high specificity to a unique site on the RNA, a single stem-loop
      structure, containing the initiation codon of the gene for the viral replicase.
      In order to determine the structure of these protein-RNA complexes, we have used
      chemically synthesized variants of the stem-loop fragment and soaked them into
      crystals of recombinant capsids. The RNA stem-loop, as bound to the protein,
      forms a crescent-like structure and interacts with the surface of the beta-sheet
      of a coat protein dimer. It makes protein contacts with seven phosphate groups on
      the 5' side of the stem-loop, with a pyrimidine base at position -5, which stacks
      onto a tyrosine, and with two exposed adenine bases, one in the loop and one at a
      bulge in the stem. Replacement of the wild-type uridine with a cytosine at
      position -5 increases the affinity of the RNA to the dimer significantly. The
      complex with RNA stem-loop having cytosine at this position differs from that of
      the wild-type complex mainly by having one extra intramolecular RNA interaction
      and one extra water-mediated hydrogen bond.

PMID- 9245602
TI  - Reduction in the amide hydrogen exchange rates of an anti-lysozyme Fv fragment
      due to formation of the Fv-lysozyme complex.
AB  - The Fv fragment of the monoclonal antibody D1.3 was expressed in bacteria.
      Standard triple resonance techniques were used to obtain the NMR resonance
      assignments for 211 out of 215 backbone 15N/NH atoms for D1.3 Fv. Using these
      assignments, hydrogen exchange rates are measured for 82 amide hydrogen atoms in
      D1.3 Fv free and bound to hen egg-white lysozyme. Upon binding to antigen,
      exchange rates are decreased for residues throughout the Fv. Many of these
      residues are located remote from the site of interaction with the antigen. These
      changes are larger than previously observed for the antigen portion of the
      complex. Evidently, the beta-sheet structure of the Fv propagates the effects of
      binding more efficiently than the antigen. These effects are compared between the
      three different polypeptide chains that make up the complex. These data suggest
      that reduced dynamics are a general feature of antibody binding to antigen.

PMID- 9245603
TI  - A comparison of the folding kinetics and thermodynamics of two homologous
      fibronectin type III modules.
AB  - The homologous ninth and tenth type III modules of human fibronectin share
      identical topologies and nearly identical core structures. Despite these
      structural similarities, the refolding characteristics of the two modules, which
      have a sequence identity of less than 30 %, are very different; in the absence of
      denaturant the ninth module folds several hundred times more slowly than the
      tenth and, although both modules contain numerous proline residues, only the
      ninth exhibits a slow, proline isomerization-limited folding phase. The different
      folding kinetics of the two modules coincide with a large difference in their
      thermodynamic stability, with the folding free energy of the tenth being
      approximately five fold greater than that of the ninth. This may be the reason
      why the ninth module, unlike the rapidly folding tenth module, is apparently
      unable to overcome characteristics of the fibronectin type III modules that can
      slow the folding process. The non-proline-limited folding kinetics are, however,
      very similar for the two modules when compared under conditions where their
      overall stabilities are similar. The significance of this finding is discussed in
      terms of possible determinants of the kinetics of protein folding.

PMID- 9245604
TI  - Folding and stability of a fibronectin type III domain of human tenascin.
AB  - The folding of an isolated fibronectin type III domain of human tenascin, a large
      extra-cellular matrix protein, has been characterised. The isolated module, which
      has no disulphide bonds, can be reversibly unfolded by chemical denaturant and
      temperature. Equilibrium unfolding, measured using a number of different probes,
      fits to a two-state transition, with consistent measures of DeltaGH2OD-N. Folding
      and refolding rate constants have been determined over a range of denaturant
      concentrations. The refolding kinetics are bi-phasic, and in the transition
      region the slow phase dominates refolding kinetics. Outside the transition region
      the folding of the fast-folding species fits to a two-state model. There is no
      evidence for significant accumulation of partially folded intermediates.

PMID- 9245606
TI  - Commentary

PMID- 9245605
TI  - Commentary

PMID- 9245607
TI  - EDITORIAL

PMID- 9245608
TI  - p24 antigen capture assay for quantification of human immunodeficiency virus
      using readily available inexpensive reagents.
AB  - Antigen capture enzyme-linked immunosorbent assay (ELISA) for quantitation of the
      p24 gag protein of human immunodeficiency virus type-1 (HIV-1) is currently the
      most common method used to demonstrate virus replication both in vivo and in
      vitro. The present paper describes an ELISA employing readily available
      inexpensive reagents and gives detailed suggestions for optimizing the variables
      for specific purposes. The assay is as sensitive as commercial kits (25 pg/ml)
      and has a linear dose response over a wide range of p24 concentrations (25-1000
      pg/ml). For these reasons, as well as its low cost, this assay has proven useful
      in a variety of research applications. This assay also has been found to be
      effective in detecting the gag protein of human immunodeficiency virus type-2 and
      simian immunodeficiency virus.

PMID- 9245609
TI  - Quantitative competitive RNA PCR for quantitation of virion-associated HIV-1 RNA.
AB  - Quantitative competitive PCR is a highly sensitive technique that allows accurate
      quantitation of small amounts of RNA. We have modified the original method to
      include the use of an internal standard at all stages of sample analysis. In this
      way, the method can accommodate for variations in the recovery of viral particles
      and in the isolation of genomic RNA as well as provide a suitable competitive
      substrate during quantitative RNA PCR. We have used this method to characterize
      changes in virus load in plasma of HIV-1-seropositive individuals following their
      vaccination against opportunistic infections.

PMID- 9245610
TI  - Resting cell neutralization assay for HIV-1 primary isolates.
AB  - A technique is described for detecting the activity of neutralizing polyclonal or
      monoclonal antibodies against HIV-1 primary isolates. Most commonly, neutralizing
      antibody activity for HIV-1 is assessed by quantifying the ability of antibodies
      to inhibit virus infection in mitogen-activated peripheral blood mononuclear
      cells or transformed lymphocytes. Because the target of HIV infection in vivo is
      neither a mitogen-activated nor a transformed cell, an assay using unstimulated
      peripheral blood mononuclear cells as a more physiologic target cell was
      developed. This "resting cell assay" mainly utilizes primary HIV-1 isolates that
      have been carried for only a few passages in vitro. The result is an assay that
      is more efficient to perform and that detects neutralizing activity with
      comparable or greater sensitivity than that previously described for assays of
      primary HIV-1 isolates.

PMID- 9245611
TI  - In vitro assays for activities of retroviral integrase.
AB  - Integration of retroviral DNA, an essential step during the retroviral life
      cycle, is mediated by the viral protein integrase. Simple in vitro assays for
      measuring integrase activities are described, including catalysis (3'-end
      processing, 3'-end joining, disintegration), juxtaposition of viral DNA ends, DNA
      binding, and target site selection. The described assays will be useful in
      elucidating the molecular mechanism of retroviral integration and screening for
      integrase inhibitors as potential anti-retroviral drugs.

PMID- 9245612
TI  - Genetic selection in Escherichia coli for active human immunodeficiency virus
      reverse transcriptase mutants.
AB  - Most catalytically active human immunodeficiency virus (HIV) reverse
      transcriptase (RT) mutants characterized to date have been isolated from the
      virus after treatment with HIV RT inhibitors such as nucleoside analogs. However,
      detailed understanding of structure-function relationships, and of the roles of
      the several catalytic activities of HIV RT in viral replication, requires
      characterization of a greater diversity of mutant enzymes than has been obtained
      from viral variants. Coupling of a bacterial genetic selection system for
      functional HIV RT with random mutagenesis has yielded a large number of active
      mutant enzymes, most of which have not been found in viral variants. The genetic
      selection system, combined with biochemical characterization of active mutant
      proteins, affords three major benefits. First, we can increase our understanding
      of the roles of individual amino acids in catalysis. Second, the mutational
      spectrum observed among active HIV RT variants can identify amino acids that are
      intolerant, or relatively intolerant, of substitution. Third, this system
      provides us with HIV RT variants with altered biochemical properties, such as
      replicational fidelity and processivity. Characterization of HIV harboring these
      mutant RTs with defined structural and functional alterations will contribute to
      elucidation of the roles of each catalytic activity of HIV RT in viral
      replication.

PMID- 9245613
TI  - Use of single-cycle analysis to study rates and mechanisms of retroviral
      mutation.
AB  - Retroviruses evolve at rapid rates. This allows them to escape immune
      surveillance, thwarts vaccine development, and leads to rapid emergence of drug
      resistant virus. Information regarding the retroviral mutation rates and the
      underlying mechanisms of mutagenesis will undoubtedly expedite the development of
      strategies to combat retroviral-mediated diseases. In this review, we discuss how
      the unique retroviral life cycle can be adapted such that retroviral variation
      can be studied in a single cycle of replication. By limiting replication to a
      single cycle, retroviral mutation rates can be directly measured, and the
      consequences of mutations can be observed. In addition, retroviral recombination
      rates as well as the nature of primer strand transfer during reverse
      transcription can be studied using this system. Molecular analysis of the
      spectrum of mutations arising during a single cycle of virus replication also
      sheds light on the mechanisms of mutagenesis and retroviral replication.

PMID- 9245614
TI  - Production of high-titer human immunodeficiency virus type 1 pseudotyped with
      vesicular stomatitis virus glycoprotein.
AB  - We describe a method for the production of high-titer stocks of human
      immunodeficiency virus type 1 (HIV-1) pseudotyped with vesicular stomatitis virus
      envelope glycoprotein (VSV G). VSV G pseudotypes provide several advantages over
      other retroviral envelope proteins. The VSV G envelope is mechanically stable,
      enabling ultracentrifugal concentration of virions to high titers, and VSV G has
      a broad host range, enabling infection of many mammalian and nonmammalian cell
      types. VSV G pseudotypes of HIV-1 are useful for the study of HIV infection and
      replication kinetics and for the study of the function of specific viral
      proteins. We describe applications for the study of HIV-1 using VSV G
      pseudotypes. Additionally, we describe a method for pseudotyping retroviral
      vectors with VSV G. The same advantages of VSV G pseudotypes of HIV-1 apply to
      retroviral vectors; VSV G pseudotyped retroviral vectors may be used to introduce
      genes of interest into a wide variety of cell lines.

PMID- 9245615
TI  - Preparation and maintenance of SCID-hu mice for HIV research.
AB  - The SCID-hu mouse bearing a functional human thymic implant can be easily
      infected with HIV. Infection results in virus replication and relatively rapid
      depletion of CD4+ human thymocytes, resulting in a pathologic profile similar to
      that seen in the thymus of HIV-infected humans. The use of the SCID-hu model for
      HIV research requires protection of the animals from opportunistic infections and
      protection of the operators from human pathogens. This discussion describes
      reliable methods of animal care and surgical procedures to meet these needs.

PMID- 9245616
TI  - Tracking changes in HIV-1 envelope quasispecies using DNA heteroduplex analysis.
AB  - A DNA heteroduplex tracking assay (HTA) using single-stranded probes is
      described. This assay provides a rapid means of resolving genetic variants
      coamplified by PCR and of measuring the level of particular variants in complex
      populations. To confidently detect minor quasispecies changes, the importance of
      maximizing template input into nested PCR (nPCR) and of duplicating nPCR and HTA
      to ensure correct population sampling is highlighted. The sensitivity of
      detection of rare variants within a genetically mixed population using single
      stranded DNA probes is shown to be 1:500. The effects of nucleotide substitution
      at different locations on heteroduplex electrophoretic mobility are used to
      illustrate the limits of HTA for mutation detection. This simple assay may be
      used to track the evolution of HIV as well as to address issues of contamination
      and transmission.

PMID- 9245617
TI  - Cloning and sequence analysis of the fimbriae associated protein (fap) gene from
      Actinobacillus actinomycetemcomitans.
AB  - Fimbrial-associated protein, an attachment factor of Actinobacillus
      actinomycetemcomitans, was genetically analysed by cloning. The plasmid obtained
      was found to harbor a 1.7kb fragment which contained a 228bp open reading frame
      encoding 76 amino acids (7.970kDa). The fimbriae associated protein gene (fap)
      was strongly expressed in fimbriated A. actinomycetemcomitans 310a but not in non
      fimbriated strains.

PMID- 9245618
TI  - Sequence analysis of the structural tbpA gene: protein topology and variable
      regions within neisserial receptors for transferrin iron acquisition.
AB  - The gene coding for the 98-kDa meningococcal outer membrane transferrin binding
      protein 1 (TbpA) from strain B385 was cloned and sequenced. Sequence comparison
      among its deduced aminoacid sequence and those from TbpA and the closely related
      LbpA (lactoferrin binding protein) gene from three different meningococcal
      strains, and four isolates from two other bacterial pathogens, showed that TbpA
      variability is confined to five specific segments, designated VR1 (199-287), VR2
      (306-381), VR3 (480-546), VR4 (618-651) and VR5 (681-708). The third VR was the
      most variable among strains both at the nucleotide and amino acid levels. Six
      additional tbpA genes from different meningococcal strains were cloned and its
      VR3 sequence determined. On the basis of this data we were able to cluster tbpA
      genes in two groups: D (bearing a deletion in VR3) and N (nondeleted); all N and
      D strains belonging to the groups of high or low molecular weight transferrin
      receptor isotype, respectively. However, by phenogram analysis, the prototypical
      strain M982 (Group II) was clustered with M990 (B16B6 isotype, Group I). These
      results point to the existence of important exposed regions as well as to the
      possibility of horizontal gene exchange involving this locus. A topology model
      with 14 exposed loops and 28 membrane spanning segments was postulated. According
      to this tentative analysis, TbpA as well as LbpA proteins should form a gated
      channel in the neisserial outer membrane. The variable regions were located in
      the fifth, sixth, eighth, 10th and 11th loops respectively. Among TbpAs VR1, VR2,
      and VR3 resulted the most relevant regions.

PMID- 9245619
TI  - Acanthamoeba castellanii metabolites increase the intracellular calcium level and
      cause cytotoxicity in wish cells.
AB  - Previous studies have shown that trophozoites of the pathogenic free-living
      amoeba Acanthamoeba castellanii rapidly lyse a variety of cells in vitro.
      However, the role played by cytolitic molecules that may participate in
      Acanthamoebal cytopathogenicity has yet to be completely elucidated. The aim of
      this work was to study whether soluble molecules released by A. castellanii
      trophozoites could induce cytopathic effect in human epithelial cells in vitro.
      The results obtained indicate that A. castellanii trophozoites constitutively
      elaborate and release soluble factors that immediately elicit a cytosolic free
      calcium increase in target cells. This phenomenon is induced by low molecular
      weight amoebic metabolites and depends on a transmembrane influx of extracellular
      calcium. Morphological changes, cytoskeletal damage, cell death and cytolysis
      followed the elevation of cytosolic free-calcium levels. Calcium ions are very
      important for cell homeostasis, in fact, they control the functions of a variety
      of cellular responses, including secretion, cell proliferation and apoptosis. Our
      results suggest that the substained elevation of the cytosolic free-calcium in
      response to A. castellanii metabolites might play a fundamental role in target
      cell damage during Acanthamoeba infections.

PMID- 9245620
TI  - Species-specific B-cell epitope on the C-terminal region of the alpha antigen
      from Mycobacterium scrofulaceum.
AB  - In the amino acid (AA) sequences of alpha antigen from mycobacteria, C-terminal
      regions were variable among a variety of mycobacterial species though the N
      terminal regions were relatively conserved. These regions may possess some
      species-specific antigenic determinants of the alpha antigen from Mycobacterium
      scrofulaceum (S-alpha). AAs288-300 of S-alpha fused to beta-galactosidase was
      reactive with the antisera raised against S-alpha. The same fused peptide did not
      react with the antisera raised against the alpha antigen from Mycobacterium avium
      (A-alpha) and Mycobacterium bovis BCG (B-alpha). B-cell epitope mapping then was
      performed focusing on the C-terminal region of S-alpha using the synthetic
      peptides. Their reactivities with antisera raised against the alpha antigens of
      three different mycobacterial species were assessed by ELISA. AAs279-286 were a
      cross-reactive common immunodominant region among three mycobacterial species.
      This region may be one of the cross-reactive common epitopes in mycobacterial
      species. And AAs291-300 were reactive only with the antisera raised against S
      alpha. This region may possess a species-specific epitope.

PMID- 9245621
TI  - CD8alphaalpha T cells in lesions of Listeria monocytogenes-infected beta2m
      deficient mice.
AB  - The beta2-microglobulin (beta2m)-deficient mutant mice lack alphabeta TCR
      CD8alphabeta T cells. We found markedly impaired granuloma formation in Listeria
      monocytogenes-infected beta2m-/- mice. Abundant CD8alphaalpha T cells were
      identified in loosely structured infiltrative liver lesions. Microfluorescence
      analysis disclosed that these CD8alphaalpha T cells expressed mostly the
      gammadelta TCR. CD8alphaalpha T cells were also found in the spleen of Listeria
      infected beta2m-/- mice. These data provide first evidence for CD8alphaalpha T
      cells in listerial lesions of beta2m-/- mice.

PMID- 9245622
TI  - Flagella are a positive predictor for virulence in Legionella.
AB  - Pathogenesis of Legionnaires>> disease is strictly related to the ability of the
      legionellae to infect phagocytic cells, yet surface markers of virulence in
      Legionella isolates are currently unknown. Rabbit antibodies raised against
      purified flagella of Legionella pneumophila serogroup 1 recognized a total of 24
      of 30 laboratory-maintained isolates of L. pneumophila serogroups 1-15 and 16 of
      24 other Legionella species tested by rapid immunoblot and indirect
      immunofluorescence assay. All isolates possessing flagella detectable with these
      anti-flagella antibodies, regardless of species, were capable of infecting
      Hartmannella vermiformis. Isolates lacking immunologic cross-reactivity were
      shown to lack purifiable flagella. The majority of aflagellate isolates were not
      motile and failed to multiply intracellularly in co-culture with Hartmannella
      vermiformis. Some isolates characterized as aflagellate when harvested from BCYE
      agar were able to multiply in amoebae, and flagella were subsequently detectable
      by immunologic methods. These data suggest that lack of immunologic recognition
      of flagella in laboratory-maintained isolates of Legionella is due to their
      attenuation and a corresponding loss of expression of flagella. More importantly,
      the presence of flagella can serve as a positive predictive marker for strain
      virulence and is useful in determining the virulence status of Legionella
      isolates.

PMID- 9245623
TI  - Role of type 1 fimbriae in EPEC infections.
AB  - Several fimbriae have been implicated as potentially important in EPEC adhesion
      and pathogenesis. EPEC strain E2348/69 produced only bundle forming pili and type
      1 fimbriae, and did not produce other accesory adhesins identified in EPEC strain
      B171. Cloning and mutagenesis of these EPEC fim genes indicated that type 1 pili
      had no affect on levels or patterns of adhesion to cultured human cells.

PMID- 9245624
TI  - Kinetics of the ascension of NTHi from the nasopharynx to the middle ear
      coincident with adenovirus-induced compromise in the chinchilla.
AB  - To determine the kinetics of ascension of the eustachian tube (ET) by non
      typeable Haemophilus influenzae (NTHi) in situ from the nasopharynx to the middle
      ear using an experimental model of otitis media (OM), we examined snap-frozen
      sections of chinchilla ET and middle ear mucosa for adherent bacteria over a 14
      day time period. Via fluorescent- and transmission electron-microscopy, we found
      that NTHi preferentially adhered not to the epithelial cells but to the mucus in
      the ET and gradually ascended this tubal organ, reaching the middle ear
      approximately 10 days after intranasal inoculation of adenovirus-infected
      animals. The number of NTHi adherent to mucus at the pharyngeal portion of the ET
      increased significantly in the first 4 days after inoculation of the nares
      whereas the number of adherent bacteria in both the mid and tympanic portions of
      the ET increased more gradually over time. NTHi were not observed in the middle
      ear until approximately 7-10 days after inoculation of the nares which was
      coincident with the onset of clinical signs of OM. These data confirmed our
      earlier in vitro investigation which suggested that adherence to and growth
      within stagnant mucus within a ET compromised by adenovirus was a possible
      mechanism by which NTHi, resident in the nasopharynx, might gain access to the
      middle ear and induce OM.

PMID- 9245627
TI  - ADRF differential cross polarization spectroscopy of synthetic calcium phosphates
      and bone mineral.
AB  - An adiabatic demagnetization in the rotating frame (ADRF) differential cross
      polarization (DCP), or inversion recovery cross polarization (IRCP), technique
      has been developed to study synthetic calcium phosphates and bone mineral. ADRF
      of the protons followed by a remagnetization of the phosphorus-31 spins results
      in an equalization of the dipolar and phosphorus Zeeman nuclear spin
      temperatures. By shifting the phase of the phosphorus RF by 180 degrees during
      the forward cross polarization it is possible to invert the temperature of this
      reservoir and initiate reverse cross polarization. Transient Strombotne-Hahn
      oscillations were observed on inverting the temperature. The presence of these
      oscillations complicates the determination of a null point on the basis of cross
      polarization times. It is necessary to shift the phase of the RF only after a
      Zeeman spin temperature can be defined, and to use an RF field strength that is
      slightly smaller than the equivalent S-spin local dipolar field in order to
      produce a zero crossing after the transient oscillations have decayed.

PMID- 9245630
TI  - Solution NMR characterization of hydrogen bonds in a protein by indirect
      measurement of deuterium quadrupole couplings.
AB  - Hydrogen bonds stabilize protein and nucleic acid structure, but little direct
      spectroscopic data have been available for characterizing these critical
      interactions in biological macromolecules. It is demonstrated that the electric
      field gradient at the nucleus of an amide hydrogen can be determined residue
      specific by measurement of 15N NMR relaxation times in proteins dissolved in D2O,
      and uniformly enriched with 13C and 15N. In D2O, all backbone amide protons can
      be exchanged with solvent deuterons, and the T1 relaxation rate of a deuteron is
      dominated by its quadrupole coupling constant (QCC), which is directly
      proportional to the electric field gradient at the nucleus. 2HN T1 relaxation can
      be measured quantitatively through its effect on the T2 relaxation of its
      directly attached 15N. QCC values calculated from 2HN T1 and previously reported
      spectral densities correlate with the inverse cube of the X-ray crystal structure
      derived hydrogen bond lengths: QCC = 228 + Sigmai 130 cos alphai/ri3 kHz, where
      alpha is the N-H...Oi angle and r is the backbone-backbone (N-)H...Oi(=C)
      hydrogen bond distance in angstroms.

PMID- 9245631
TI  - Dynamic T1 measurement using snapshot-FLASH MRI.
AB  - The application of an inversion-recovery snapshot FLASH (fast low-angled shot)
      imaging sequence to the dynamic measurement of monoexponential T1 relaxation was
      investigated. The effect of (a) a reduction in the overall sequence repetition
      time, and (b) an increase of the read-pulse flip angle, on the measurement of T1
      was analyzed. The error in T1 introduced by these factors is calculated, and a
      fuller analysis that takes them into account is presented. Data from a phantom
      are used to confirm this analysis. The magnitude of the errors is illustrated by
      measuring myocardial T1 in patients with acute ischaemic heart disease during the
      injection of a bolus of the contrast medium gadobenate dimeglumine. Overall,
      there was a 10% difference between the T1 values when the approximate and exact
      solutions were used; this was statistically significant. However, the difference
      was on average 25% for patients with a high heart rate (because of the shorter
      sequence-repetition time) in areas of infarcted myocardium (because of the longer
      T1).

PMID- 9245632
TI  - A solenoid-like coil producing transverse RF fields for MR imaging.
AB  - A solenoidal RF coil is presented that generates an RF field only perpendicular
      to the long axis, so that it can be used longitudinally in the usual
      superconducting solenoid magnet for NMR. This new design is superior to the
      traditional saddle coil or Helmholtz pair. Applications for the coil will include
      imaging of legs, arms, etc., as well as analytical application in high-resolution
      NMR. A tilted single-turn-solenoid, which has the plane of each loop tilted with
      respect to the cylinder axis, is implemented to generate an RF field with a
      component perpendicular to the coil-cylinder axis. The novel addition of an eddy
      current coil eliminates the undesirable longitudinal component of the RF field,
      leaving an RF field entirely perpendicular to the coil-cylinder axis. By
      inserting the eddy coil, the spatial homogeneity of the transverse RF field is
      greatly improved, with significant increases in the H1 field strength and
      receiving sensitivity. Images with the eddy-coil-modified tilted solenoid are
      remarkably uniform in intensity over a large useful volume.

PMID- 9245637
TI  - Evaluation of multiple-quantum-filtered 23Na NMR in monitoring intracellular Na
      content in the isolated perfused rat heart in the absence of a chemical-shift
      reagent.
AB  - The feasibility of employing triple-quantum-filtered (TQF) or double-quantum
      filtered (DQF) 23Na NMR spectra to monitor intracellular Na (Nain) content in
      isolated rat hearts perfused in the absence of a chemical-shift reagent (SR) was
      investigated. This necessitated characterization of the following: first, the
      pool of Nain represented by the intracellular TQF (TQFin) spectrum; second, the
      maximum extent to which altered transverse relaxation times affect TQFin spectral
      amplitudes; and finally, the situations for which the SR-free method can reliably
      be applied. The rates of increase in peak amplitudes of both intracellular TQF
      spectra, adjusted for changes in both fast (T2f) and slow (T2s) transverse
      relaxation times, and intracellular single-quantum (SQin) spectra were identical
      during no-flow ischemia, indicating that TQFin and SQin spectra represent the
      same Nain population. Addition of an Na/K ATPase inhibitor, ouabain (>/=500
      microM), and no-flow ischemia induced similar rates of increase of Nain content.
      However, the Nain level for which the T2 values started to increase was lower for
      ischemic (<140% of preischemic values) than for ouabain-exposed (>165%) hearts,
      which is consistent with the known earlier onset of intracellular swelling in
      ischemic hearts. Exposure of hearts to hyperosmotic perfusate (200 mM sucrose)
      increased [Nain], due to a decreased cell volume and an unchanged Nain content,
      but caused a decrease in T2 values, a trend opposite to that observed with
      exposure of hearts to ouabain or ischemia. T2 values therefore consistently
      correlated only with cell volume, not with Nain content or concentration,
      indicating an important role for intracellular macromolecule concentration in
      modulating transverse relaxation behavior. The combined effect of ischemia
      induced increases in T2 values and their inhomogeneous broadened forms was an
      approximately 6% overestimation of Nain content from amplitudes of SR-aided TQFin
      spectra, indicating negligible effect of transverse relaxation-dependent
      alterations on TQFin spectral amplitudes. Thus, Nain content may be reliably
      determined from SR-free TQF spectra when the contribution from extracellular Na
      does not appreciably vary, such as during constant pressure perfusion. Following
      complete reduction in perfusion pressure, both SR-free TQF and DQF spectra
      respond to increases in Nain content. However, SR-free DQF NMR provides an
      estimate of Nain content much closer to that provided by the SR-aided method, due
      to the appreciable decrease of the extracellular DQF signal resulting from
      destructive interference between second- and third-rank tensors.

PMID- 9245639
TI  - Enzyme-histochemical study on postnatal development of rat stomach lymphatic
      vessels.
AB  - Postnatal development of rat gastric lymphatics was studied by an enzyme
      histochemical method to elucidate the morphological changes of lymphatics and
      their relationship to maturation and function, especially in the glandular
      portion. The significant features of 5'-Nase-positive lymphatics in distribution
      and structure were examined in different stages (within 24 hr, 4-21 days, and 2
      months). Lymphatics in the greater curvature and anterior wall grew much slower
      than those in the lesser curvature and posterior wall of the stomach in newborn
      and infant rats. Lymphatic islands isolated from the primary lymphatic networks
      in the submucosa and subserosa underwent a morphological change during this early
      period. This is considered one of the basic steps in lymphatic development.
      Occurrence of lymphatic networks in the deep lamina propria indicates that
      development in the gastric wall is well characterized from Day 10. With further
      growth and modification of lymphatics, the networks in the different layers
      formed an extensive communication network and many lymphatic valves were found in
      the submucosa and subserosa. Pinocytotic vesicles, open junctions, and
      intraendothelial channels were frequently detected in the mucosal and submucosal
      lymphatic networks of the corpus-antrum and antrum-duodenum divisional zones in
      the adult rats. These findings suggest that developing lymphatics in the rat
      stomach may represent rapidly growing tissue not only with high 5'-Nase activity
      but also with high adaptability for future physiological demands.

PMID- 9245640
TI  - Lumen formation and other angiogenic activities of cultured capillary endothelial
      cells are inhibited by thrombospondin-1.
AB  - The large secreted glycoprotein thrombospondin-1 is a potent inhibitor of
      neovascularization in vivo. In order to better understand its mechanism of
      action, we have determined the full range of deficits thrombospondin can impose
      on cultured capillary endothelial cells. Exogenously added thrombospondin-1
      blocked the ability of these cells to organize into cords. It blocked the
      migration of endothelial cells and vascular smooth muscle cells, but not that of
      fibroblasts, neutrophils, or keratinocytes, demonstrating specificity.
      Conversely, when the endogenous thrombospondin-1 produced by the endothelial
      cells was inactivated using antibodies that can neutralize its inhibition of
      neovascularization in vivo, migration toward basic fibroblast growth factor and
      cord formation were stimulated, and sparsely plated cells developed cylindrical
      cavities. These cavities formed by vesicle fusion, extended the depth of the
      cell, and appeared to be incipient lumens, staining positively for the luminal
      marker angiotensin converting enzyme. Antiangiogenic levels of thrombospondin-1
      had no measurable effect on the overall level of activity of soluble gelatinases
      or on urokinase plasminogen activator produced by activated endothelial cells.
      Coupled with previously published data, these results demonstrate thrombospondin
      1 is a multifaceted inhibitor able to block the entire program of
      dedifferentiation and redifferentiation essential to the formation of new
      vessels. They also support the contention that the endogenously produced protein
      contributes to the quiescence of the normal vasculature.

PMID- 9245641
TI  - Synergistic interactions between neuropeptide and histamine on the capillary
      permeability in rat skin: evaluation by reflectance spectrophotometry.
AB  - Effects of neuropeptides on capillary permeability and their interactions with
      histamine (HIS) in rat skin were investigated. The capillary permeability was
      measured continuously by reflectance spectrophotometry after intravenous (iv)
      injection of Evans blue dye. The capillary permeability was increased dose
      dependently by the intradermal injection of HIS (0.3-100 microg/site) and
      substance P (SP; 25-250 ng/site). Calcitonin gene-related peptide (80-800
      ng/site) elicited a significant but less increase than did SP. Capsaicin (30
      microg/site) also increased capillary permeability slightly but significantly,
      suggesting the release of endogenous neuropeptides. Both diphenhydramine (DPH; 3
      mg/kg, iv) and cimetidine (CIM; 30 mg/kg, iv) reduced HIS-induced responses. DPH
      also reduced the SP-induced response significantly, but CIM did not. An SP
      antagonist, [D-Pro2, D-Trp7,9]-SP (1.3 mg/kg, iv), reduced not only SP- but also
      HIS-induced responses. Furthermore, the HIS-induced response was attenuated by
      pretreatment with epicutaneous capsaicin for 4 days, depleting endogenous SP.
      These results delineate the synergistic interactions between SP and HIS in rat
      skin and suggest the participation of neuropeptides in increasing capillary
      permeability.

PMID- 9245642
TI  - Effects of hypoxia and hypercapnia on capillary flow velocity in the rat cerebral
      cortex.
AB  - The velocity of red blood cells (RBC) in individual capillaries of the rat
      cerebral cortex was assessed using direct, intravital video microscopy under
      normal conditions and during systemic hypoxia or hypercapnia. The movement of RBC
      in capillaries within 50-microm depth of the parietal cortex was visualized with
      the aid of fluorescent labeling of RBC in a closed cranial window preparation in
      pentobarbital-anesthetized, artificially ventilated adult rats. Hypoxia was
      produced by lowering the concentration of oxygen in the inspired gas from 30 to
      15% for 5 min. Hypercapnia was achieved by increasing the inspired CO2
      concentration (FiCO2) from 0 to 5% and then to 10% for 5 min at each level. The
      mean arterial pressure was maintained constant during both maneuvers. Under
      control conditions, fast and heterogeneous RBC flow in multioriented, tortuous
      capillaries was observed. During hypoxia, RBC velocity increased from 0.61 +/-
      0.06 to 0.82 +/- 0.10 mm/sec (35% change). During hypercapnia, RBC velocity
      increased from 0.73 +/- 0.05 to 1.07 +/- 0. 11 mm/sec (46% change) at 5% CO2 and
      to 1.19 +/- 0.11 mm/sec (63% change) at 10% CO2. Corresponding changes in
      regional blood flow as assessed by laser-Doppler flowmetry during hypercapnia
      were 69 +/- 7 and 128 +/- 21%, respectively. The RBC velocity increased in almost
      all capillaries during hypoxia and during moderate hypercapnia. However, a
      substantial number of capillaries showed no change or a small decrease in RBC
      velocity during severe hypercapnia. A significant negative correlation between
      the velocity change at 10% CO2 and the normocapnic resting velocity was found in
      a group of capillaries isolated by cluster analysis. These results suggest that
      the dominant component of cerebral hyperemic response to hypoxia and to moderate
      hypercapnia is an increase in capillary RBC flow velocity. A more complex change
      in the velocity distribution occurs during severe hypercapnia and results in
      increased homogeneity of RBC perfusion in the cerebrocortical capillary network.

PMID- 9245643
TI  - Role of leukocytes in diabetic microcirculatory disturbances.
AB  - Various rheological abnormalities of the blood have been widely reported in
      diabetes. However, it remains unclear which one affects blood flow at the level
      of microcirculation, an important site in the pathogenesis of diabetic
      microangiopathy. To differentiate which blood component leads to microcirculatory
      disturbances in diabetes, we studied the hemorheological properties of diabetic
      patients using an array flow analyzer that has microchannels simulating
      capillaries. Venous blood was collected from 19 diabetic patients and 24 control
      subjects. Three blood samples were prepared: plasma alone, erythrocyte suspension
      (ES) at 10% hematocrit (Ht), and erythrocyte and leukocyte suspension (ELS)
      having leukocyte counts of 1000/microl at 10% Ht. These samples were forced to
      flow through microchannels (equivalent diameter 6 micron, equivalent length 30
      micron, 2600 in parallel) by applying a pressure difference of 20 cm H2O. Transit
      times for 100 microl of samples were measured, and the flow behavior of cells
      through the microchannels was recorded with a video-microscope. The transit time
      of ELS was 52.5 +/- 6.2 sec (mean +/- SD) in the diabetic group and 47.7 +/- 3.3
      sec in the control group; there was significant prolongation in the transit time
      of diabetic ELS (P = 0.005), whereas the transit times of plasma alone and ES
      showed no significant differences between control and diabetic groups. Leukocytes
      were occasionally observed to plug the microchannels during the measurements of
      ELS from some diabetic patients. Our results imply that reduced deformability of
      leukocytes in diabetes may contribute to flow disturbances in the
      microcirculation. Leukocytes could play a potential role in the pathogenesis of
      diabetic microangiopathy.

PMID- 9245644
TI  - Vessels supplying septa and tendons as functional shunts in perfused rat
      hindlimb.
AB  - An assessment was made of the relationship between vasoconstrictor-mediated
      changes in metabolism and the apparent flow in putative nonnutritive vessels of
      muscle located on tendon. Surgically isolated rat hindlimbs were perfused at
      constant flow while monitoring perfusion pressure and venous pO2. In addition
      exposed tibial tendon vessels of the biceps femoris muscle of the perfused leg
      were positioned either under a surface fluorometer probe to monitor signal
      strength when pulses of fluorescein isothiocyanate dextran were infused or over
      the objective lens of an inverted microscope for photography when pulses of India
      ink were infused. Measurements were conducted under steady state with vehicle,
      norepinephrine, or serotonin infused. Norepinephrine increased perfusion pressure
      and oxygen uptake (VO2), but decreased fluorescence signal from the tendon
      vessels. Photomicroscopy confirmed that the vessels had generally decreased in
      diameter. Serotonin also increased perfusion pressure but decreased VO2 and
      increased fluorescence signal from the tendon vessels. Photomicroscopy confirmed
      that serotonin infusion had led to a marked increase in diameter of the vessels.
      It is concluded that a reciprocal relationship exists between resting muscle
      metabolism as controlled by vasoconstrictors and flow-through muscle tendon
      vessels.

PMID- 9245645
TI  - Interleukin-1-alpha and de novo mammalian angiogenesis.
AB  - In the literature, the role of interleukin-1 (IL-1) as an angiogen is
      controversial. The ability of IL-1-alpha to induce de novo angiogenesis in adult
      rats was studied using the mesenteric window angiogenesis assay (MWAA). Murine
      recombinant IL-1-alpha was injected intraperitoneally twice daily on Days 0 to 4
      at 11.8 pM, 118 pM, and 1.18 nM and groups of animals were sacrificed on Days 7,
      14, 21 and 28; controls received the vehicle. Angiogenesis was quantified in
      terms of microvascular spatial extension and density using technically
      independent microscopic techniques and image analysis. Compared with the vehicle
      control, the treatment with IL-1-alpha at doses of 118 pM and 1.18 nM induced
      statistically significant angiogenesis throughout the study period, whereas IL-1
      alpha at 11.8 pM did not induce significant angiogenesis in statistical terms
      until Days 21 and 28. Compared with the previously reported angiogenic response
      to VEGF165, bFGF, IL-8, and TNF-alpha using the rat MWAA and the same
      standardized experimental protocol, the IL-1-alpha treatment displayed a higher
      degree of efficacy and potency than that of bFGF, IL-8, and TNF-alpha. Moreover,
      the duration of the significant response to IL-1-alpha exceeded that of bFGF, IL
      8, and TNF-alpha. The present data indicate that IL-1-alpha at near-physiologic
      doses is a very effective angiogenic factor in the system used here. The response
      may well be multifactorially mediated, as is discussed, and the molecular
      mechanisms which are involved remain to be clarified.

PMID- 9245646
TI  - Quantitative study of intussusceptive capillary growth in the chorioallantoic
      membrane (CAM) of the chicken embryo.
AB  - In an attempt to sort out the respective contributions of sprouting and
      intussusceptive microvascular growth (IMG) during chicken chorioallantoic
      membrane (CAM) development, we analyzed the morphology and the quantitative
      growth of the capillary bed of the CAM by light microscopy. By perfusing the CAM
      microvasculature with highly concentrated colloidal gold particles, the
      capillaries could be unambiguously distinguished from the surrounding unlabelled
      tissue. This allowed us to identify, count and measure the intercapillary tissue
      profiles. By means of morphometric analysis we could show that CAM angiogenesis
      undergoes three phases of development. In an early phase, from Day 5 to Day 7,
      the major mechanism of capillary network growth is sprouting. In an intermediate
      phase, from Day 8 to Day 12, IMG is prevailing, and at Days 13 and 14, CAM
      structure is undergoing expansion with only a small increase in complexity. These
      findings are important in view of experimental protocols using the CAM as a model
      for testing angiogenetic factors. Indeed, care has to be taken not to
      misinterpret normal age-dependent alterations of the CAM vascular architecture as
      specific responses to tested agents.

PMID- 9245647
TI  - Skin microcirculation during tapwater iontophoresis in humans: cathode stimulates
      more than anode.
AB  - The aim of this controlled study was to evaluate the influence of anode and
      cathode on skin blood flow by using direct current. Skin microcirculation and
      skin temperature of 26 healthy subjects (17 men and 9 women, 20-64 years of age)
      without any vascular diseases were registered when a tapwater iontophoresis was
      applied. Thermoindifferent water temperature was used to prevent thermic effects
      on microcirculation. The blood flow measurement was conducted by laser-Doppler
      flowmetry on the proximal forearm and on the back of the wrist. The skin
      temperature was measured before and after treatment by an infrared thermometer.
      In 19 persons there was an intense erythema on the side of the cathode and an
      only modest one on the side of the anode, while 7 persons showed meager reactions
      on both sides. The erythema rose strongly from the distal (back of the hand) to
      the proximal forearm. The comparison of the microcirculation of the arms showed
      an increase of 120% at the anode and of 700% at the cathode. The differences
      between the two sides were significant (P < 0.001). After the end of tapwater
      iontophoresis the skin temperature increased more on the side of the cathode than
      on the anode side (P < 0.001). The frequency of vasomotion did not change. The
      vasomotion amplitude increased 67% at the anode (P < 0.05) and 175% at the
      cathode (P < 0.001). The increased blood flow effect was not age or sex
      dependent. Although the increased blood flow effect was six times larger on the
      cathode side, the subjects did not perceive any subjective difference.

PMID- 9245648
TI  - Transforming growth factor beta constricts rat cremaster arterioles.

PMID- 9245649
TI  - Correlation of the fractions of proliferating tumor and endothelial cells in
      breast and colorectal adenocarcinoma is independent of tumor histiotype and
      microvessel density.

PMID- 9245650
TI  - Plasma leakage induced in postcapillary venules by the major cysteine-proteinase
      from Trypanosoma cruzi and its modulation by H1-blocker mepyramine.

PMID- 9245651
TI  - A dynamic role of the medial temporal lobe during retrieval of declarative memory
      in man.
AB  - Understanding the role of the medial temporal lobe (MTL) in learning and memory
      is an important problem in cognitive neuroscience. Memory and learning processes
      that depend on the function of the MTL and related diencephalic structures (e.g.,
      the anterior and mediodorsal thalamic nuclei) are defined as declarative. We have
      studied the MTL activity as indicated by regional cerebral blood flow with
      positron emission tomography and statistical parametric mapping during recall of
      abstract designs in a less practiced memory state as well as in a well-practiced
      (well-encoded) memory state. The results showed an increased activity of the MTL
      bilaterally (including parahippocampal gyrus extending into hippocampus proper,
      as well as anterior lingual and anterior fusiform gyri) during retrieval in the
      less practiced memory state compared to the well-practiced memory state,
      indicating a dynamic role of the MTL in retrieval during the learning processes.
      The results also showed that the activation of the MTL decreases as the subjects
      learn to draw abstract designs from memory, indicating a changing role of the MTL
      during recall in the earlier stages of acquisition compared to the well-encoded
      declarative memory state.

PMID- 9245652
TI  - An automated registration algorithm for measuring MRI subcortical brain
      structures.
AB  - An automated registration algorithm was used to elastically match an anatomical
      magnetic resonance (MR) atlas onto individual brain MR images. Our goal was to
      evaluate the accuracy of this procedure for measuring the volume of MRI brain
      structures. We applied two successive algorithms to a series of 28 MR brain
      images, from 14 schizophrenia patients and 14 normal controls. First, we used an
      automated segmentation program to differentiate between white matter, cortical
      and subcortical gray matter, and cerebrospinal fluid. Next, we elastically
      deformed the atlas segmentation to fit the subject's brain, by matching the white
      matter and subcortical gray matter surfaces. To assess the accuracy of these
      measurements, we compared, on all 28 images, 11 brain structures, measured with
      elastic matching, with the same structures traced manually on MRI scans. The
      similarity between the measurements (the relative difference between the manual
      and the automated volume) was 97% for whole white matter, 92% for whole gray
      matter, and on average 89% for subcortical structures. The relative spatial
      overlap between the manual and the automated volumes was 97% for whole white
      matter, 92% for whole gray matter, and on average 75% for subcortical structures.
      For all pairs of structures rendered with the automated and the manual method,
      Pearson correlations were between r = 0.78 and r = 0.98 (P < 0.01, N = 28),
      except for globus pallidus, where r = 0.55 (left) and r = 0. 44 (right) (P <
      0.01, N = 28). In the schizophrenia group, compared to the controls, we found a
      16.7% increase in MRI volume for the basal ganglia (i.e., caudate nucleus,
      putamen, and globus pallidus), but no difference in total gray/white matter
      volume or in thalamic MR volume. This finding reproduces previously reported
      results, obtained in the same patient population with manually drawn structures,
      and suggests the utility/efficacy of our automated registration algorithm over
      more labor-intensive manual tracings.

PMID- 9245653
TI  - The somatosensory cortex of human: cytoarchitecture and regional distributions of
      receptor-binding sites.
AB  - The aim of this study is to characterize the regional and laminar distribution
      patterns of various neurotransmitter binding sites in areas 3a, 3b, 1, and 2 of
      the human primary somatosensory cortex, and to compare these receptor-based
      "maps" with the cytoarchitectonic parcelation. Cryostat sections from a
      dorsomedial region of the postcentral gyrus close to the interhemispheric fissure
      and from a ventrolateral region close to the Sylvian fissure were examined.
      Neurotransmitter-binding sites were analyzed with quantitative in vitro receptor
      autoradiography. Different muscarinic-binding sites were labeled with
      [3H]pirenzepine and [3H]oxotremorine-M, noradrenergic-binding sites with
      [3H]prazosin, different serotoninergic-binding sites with [3H]5-hydroxytryptamine
      and [3H]ketanserine, glutamate-binding sites with l-[3H]glutamate, and GABA
      binding sites with [3H]muscimol. Adjacent sections were stained with a modified
      Nissl method for cytoarchitectonic analysis. The binding sites either were
      preferentially localized in the superficial layers ([3H]5-hydroxytryptamine,
      [3H]prazosin, l-[3H]glutamate, [3H]muscimol, and [3H]pirenzepine) or were more
      homogeneously distributed with highest densities in layers III-V
      ([3H]oxotremorine-M and [3H]ketanserine). Changes in the distribution patterns of
      [3H]oxotremorine-M- and [3H]ketanserine-binding sites precisely matched the
      borders between areas 4/3a, 3b/1, and 1/2, as defined cytoarchitectonically. In
      addition, the autoradiographs showed that area 1 possibly consists of two
      subregions which cannot be distinguished cytoarchitectonically. The results
      demonstrate that the regional and laminar distribution patterns of some, but not
      all, transmitter-binding sites are precisely correlated with the
      cytoarchitectonic parcelation of the human primary somatosensory cortex. In
      addition, binding sites may reveal new borders not detectable in Nissl-stained
      sections. Finally, the human primary somatosensory cortex differs clearly from
      the primary motor cortex due to higher densities of l-[3H]glutamate-,
      [3H]muscimol-, [3H]pirenzepine-, [3H]oxotremorine-M-, and [3H]ketanserine-binding
      sites.

PMID- 9245654
TI  - Magnetoencephalographic investigation of human cortical area V1 using color
      stimuli.
AB  - The aim of this study was to determine the response properties of the human
      visual cortex to chromatic stimuli using magnetoencephalography (MEG). Evoked
      responses were recorded to isoluminant red/green sinusoidal gratings for a wide
      range of spatial and temporal frequencies. For each condition the response was
      dominated by a single major component which was well modeled by an equivalent
      current dipole. Coregistration of MEG and MRI data provided evidence that the
      principal evoked cortical activity originated from visual area V1. To investigate
      the chromatic response properties of this area, the maximum global field power of
      the evoked response was plotted as a function of stimulus spatial and temporal
      frequency. The spatial-frequency tuning was lowpass and the temporal-frequency
      tuning was multimodal, with peaks at 0 and 4 Hz. The results demonstrate the use
      of MEG as a technique for investigating activity from discrete regions of cortex.

PMID- 9245655
TI  - Matching a computerized brain atlas to multimodal medical images.
AB  - A method for matching a digital brain anatomical atlas to multimodal medical
      images (MRI, PET, and SPET) was implemented. The digital atlas was derived from
      anatomical templates of the brain, cut according to the orbitomeatal orientation.
      The atlas consists of a set of contiguous slices schematically describing the
      brain as anatomical contours and of a set of regions of interest (ROIs)
      classifying the brain into functionally homogeneous areas. The matching procedure
      includes (a) an edge detection method for the extraction of anatomical contours
      and (b) a warping algorithm based on contour matching to fit the atlas to the
      individual brain anatomy, as described by MRI. Once the atlas is matched to MRI,
      the associated templates of ROI can be overlapped with functional PET/SPET
      studies, individually registered to MRI. The method was tested on MRI studies.
      The efficacy of the warping algorithm in overlapping atlas and MRI contours was
      assessed by calculating for each slice an index representing the extent of
      overlapping (I). Values of I in the range 0.8-0.9 were found (I = 1 complete
      overlapping). Local accuracy was also verified by comparing the position of
      correspondent anatomical ROI in the atlas and MRI images before and after
      warping. The atlas-matching procedure was applied to representative MRI/PET
      clinical images for an objective regional analysis of functional data.

PMID- 9245657
TI  - Proceedings of the Workshop on the Changing Mortality Rates of Tobacco-Related
      Diseases: ACS CPS-1 and CPS-2 Studies. New York, New York, April 15, 1996.

PMID- 9245656
TI  - Sun protection behaviors of the U.S. white population.
AB  - BACKGROUND: Sun protection behaviors are recommended to prevent skin cancer,
      which has increased in incidence. This study measured the prevalence of sun
      protection behaviors and determined personal characteristics associated with
      them. METHODS: Data from 10,048 white respondents to the 1992 National Health
      Interview Survey Cancer Control Supplement were analyzed. Multiple logistic
      regression models were constructed to relate personal characteristics to specific
      behaviors. RESULTS: Fifty-three percent of respondents reported they were "very
      likely" to use sunscreen, wear protective clothing, or seek shade if they were
      outside on a sunny day for more than 1 hr. Proportions for the individual
      behaviors were 32, 28, and 30%, respectively. Compared with people who do not
      burn, those reporting severe sunburn after 1 hr of sun exposure reported more use
      of sunscreens (odds ratio [OR] = 2.4, 95% confidence interval [CI] 2.0, 2.9),
      shade (OR = 1.8, 95% CI 1.5, 2.1), and protective clothing (OR = 2.2, 95% CI 1.9,
      2.7). Other factors associated with practicing protection behaviors included a
      personal history of skin cancer, older age, and female sex. CONCLUSIONS: A large
      percentage of white U.S. adults did not protect themselves from sun exposure.
      Additional education of the general public and persons at higher risk for skin
      cancer is needed.

PMID- 9245658
TI  - The role of nicotine in smoking-related cardiovascular disease.
AB  - Nicotine activates the sympathetic nervous system and in this way could
      contribute to cardiovascular disease. Animal studies and mechanistic studies
      indicate that nicotine could play a role in accelerating atherosclerosis, but
      evidence among humans is too inadequate to be definitive about such an effect.
      Almost certainly, nicotine via its hemodynamic effects contributes to acute
      cardiovascular events, although current evidence suggests that the effects of
      nicotine are much less important than are the prothrombotic effects of cigarette
      smoking or the effects of carbon monoxide. Nicotine does not appear to enhance
      thrombosis among humans. Clinical studies of pipe smokers and people using
      transdermal nicotine support the idea that toxins other than nicotine are the
      most important causes of acute cardiovascular events. Finally, the dose response
      for cardiovascular events of nicotine appears to be flat, suggesting that if
      nicotine is involved, adverse effects might be seen with relatively low-level
      cigarette exposures.

PMID- 9245660
TI  - Changes in mortality from smoking in two American Cancer Society prospective
      studies since 1959.

PMID- 9245659
TI  - Changing smoking patterns and mortality from chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the result of many years of
      accelerated decline in lung function in susceptible cigarette smokers. Although
      risk factors for the susceptibility of smokers to COPD have been established,
      there are still large gaps in our knowledge of the biological basis for these
      risk factors and of how to identify individuals at risk. COPD is the fourth
      leading cause of death and, in contrast to other major chronic diseases in the
      United States, has not shown declines in mortality over the past 20 years.
      Mortality trends reflect patterns of initiation of cigarette smoking that
      occurred 30 to 50 years previously. Current mortality trends indicate that COPD
      mortality may be leveling off among white males, but will continue to increase
      among women, African-Americans, and the elderly. Recent studies indicate that
      early identification of individuals with airflow obstruction and smoking
      intervention can halt the progression of COPD, but widespread screening and
      intervention programs have not yet been established.

PMID- 9245662
TI  - Nicotine regulates smoking patterns.
AB  - BACKGROUND: Since 1953, the sales-weighted average "tar" and nicotine yields of
      commercial cigarettes in developed countries have significantly declined.
      However, the risk for chronic obstructive pulmonary disease (COPD) and for cancer
      of the lung has not decreased; adenocarcinoma incidence even continues to rise
      faster than the rate of squamous cell carcinoma of the lung. Undiminished risk of
      cigarette smokers for COPD and lung cancer is largely due to more intense smoking
      and deeper inhalation of the smoke of "low-yield" cigarettes and to significant
      changes in the smoke yields of certain lung carcinogens. METHODS: Puff frequency,
      puff duration, and puff volume of cigarette smokers were determined by a
      microcomputer-assisted flow transducer. These parameters were then programmed
      into a smoking machine to generate mainstream smoke for quantifying nicotine and
      lung carcinogens. RESULTS: Simulating the human smoking characteristics increases
      the yields of "tar" and nicotine per cigarette two- to threefold above Federal
      Trade Commission-reported levels. Smoke yields of lung carcinogens like
      benzo[alpha]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone parallel
      those of nicotine and "tar." CONCLUSIONS: The way people smoke and the total
      number of cigarettes consumed daily determine the uptake, i.e., the administered
      dose of nicotine, other toxic, and genotoxic smoke constituents. It is important
      to communicate this to consumers rather than letting the smokers believe that
      they are truly smoking a cigarette of lower smoke yields when they choose "light"
      or "ultralight" products.

PMID- 9245661
TI  - The changing cigarette.
AB  - BACKGROUND: Epidemiologic surveys have revealed accelerated increases in
      adenocarcinoma but less rapid increases in squamous cell carcinoma of the lung
      among cigarette smokers in recent decades. Changes in the makeup of cigarettes
      and corresponding changes in smoke composition along with nicotine-compensating
      smoking patterns, such as the frequency of puff drawing and depth of inhalation,
      are suggested to have contributed to the observed epidemiologic profiles of these
      major histologic types of lung cancers. METHODS: The various changes in cigarette
      makeup leading to declining smoke yields from sales-weighted averages of 38 mg
      "tar" and 2.7 mg nicotine to 12 mg "tar" and 0.9 mg nicotine per cigarette are
      described. RESULTS: Higher nitrate content of tobacco blends is shown to be one
      of the major influences on lower smoke yields of carcinogenic polynuclear
      aromatic hydrocarbons (PAH) while causing increased yields of carcinogenic,
      tobacco-specific N-nitrosamines (TSNA). In vivo and in vitro bioassays
      incriminate PAH as inducers of squamous cell carcinoma, while TSNA are known to
      elicit primarily adenocarcinoma of the lung. CONCLUSIONS: The product changes,
      the smokers' dependence on nicotine which governs their smoking patterns, and the
      modified smoke chemistry support the hypothesis that differences in PAH and TSNA
      exposure may be linked to the observed different incidences of squamous cell
      cancer and adenocarcinoma of the lung.

PMID- 9245663
TI  - Changing mortality from coronary heart disease among smokers and nonsmokers over
      a 20-year interval.
AB  - A comparison of coronary heart disease (CHD) mortality in two large American
      Cancer Society studies, Cancer Prevention Study (CPS) I (1959-1965) and CPS-II
      (1962-1968) suggests that surprisingly large declines occurred in two groups so
      defined to minimize the influence of change of smoking status. CHD mortality fell
      essentially in half when comparing nearly 300,000 persons who were actively
      smoking cigarettes at entry into CPS-I with about 228,000 persons who were
      similarly actively smoking at entry into CPS-II, about 20 years later. CHD
      mortality also declined by more than 50% among nearly half a million lifelong
      nonsmokers recruited for CPS-I in the early 1960s and for CPS-II in the mid
      1980s. Possible explanations for these large declines include unmeasured
      decreases in smoking related to trial design, errors in ascertainment of causes
      of death, greater improvement among smokers of other risk factors for CHD, and
      changes in cigarettes or the pattern of smoking that have been salutary for CHD,
      but not for lung disease or lung cancer; none of these putative explanations can
      be supported by data from these studies. CHD mortality, much lower in absolute
      terms in recent years, is still much higher among smokers vs nonsmokers, so that
      the beneficial trends observed from CPS-I to CPS-II should stimulate further
      exploration of how CHD is related to smoking, and not serve as an excuse to
      ignore continued smoking.

PMID- 9245664
TI  - Trends in cigarette smoking in the United States.
AB  - Cigarette smoking in the United States increased rapidly in the 1930s and 1940s.
      In the 1950s the first reports of the health effects of cigarette smoking
      appeared and the increases in tobacco consumption were slowed down by a number of
      reports. Starting in 1973 cigarette consumption per capita decreased steadily. In
      1994, it was at the same level as in 1942. Cigarette smoking prevalence reaches a
      peak between ages 20 and 40 among both males and females and then decreases.
      Smoking prevalence is higher among males than among females and higher among
      blacks than among whites. The differences by level of education are the greatest.
      By 1993 only 25% of Americans over the age of 18 were currently smoking.

PMID- 9245665
TI  - Impact of filter cigarette smoking on lung cancer histology.
AB  - BACKGROUND: The rates of lung adenocarcinoma cancer have risen more rapidly than
      the rates of lung squamous cell cancer over the past 2 decades. METHODS: A case
      control study was carried out to assess the impact of long-term filter cigarette
      smoking on the risk of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of
      the lung. RESULTS: Odds ratios for SCC among subjects who had smoked only filter
      cigarettes were reduced relative to lifetime nonfilter cigarette smokers by 30%
      for men and by 60% for women, but no risk reduction was observed for AC of the
      lung. CONCLUSION: The predominance of AC over SCC may be due in part to the fact
      that smokers of very low yield cigarettes tend to compensate for the lower
      nicotine levels by inhaling more deeply and frequently, leading to greater
      exposure of the peripheral lung to the carcinogens in tobacco smoke, and in part
      to the increased concentration of nitrosamines that preferentially produce AC in
      laboratory animals.

PMID- 9245666
TI  - Workshop discussion panel. III: Implications of the changing tobacco-related
      mortality from COPD in the CPS-1 and CPS-2 surveys.

PMID- 9245667
TI  - Prevalence of tobacco use among Alaska Natives: a review.
AB  - BACKGROUND: Previous reports documented high rates of tobacco use among Alaska
      Natives (Eskimos, Indians, and Aleuts). In this population, tobacco use is the
      leading preventable cause of death. Lung cancer is the leading cause of cancer
      death among Alaska Natives and tobacco is responsible for over one-third of all
      cancer deaths in this population. Until recently there has been no systematic
      surveillance of the prevalence of tobacco use in this high-risk population. Data
      that did exist were not readily available to those primarily responsible for the
      health care of this population. This is the first time since 1990 that data on
      Alaska Natives have been collected in one analysis; this permits a more
      representative evaluation of tobacco use. METHODS: Data on tobacco use were
      obtained and analyzed from national and state surveys and selected research
      projects from 1988 to 1993. RESULTS: Alaska Natives have high prevalence of
      tobacco use, including both cigarettes and smokeless tobacco. Tobacco use
      prevalence among Alaska Natives exceeds that of Alaska non-Natives, U.S. whites,
      and American Indians/Alaska Natives in the United States outside of Alaska.
      Smoking prevalence among Alaska Native women is twice that of non-Native women in
      Alaska and nearly twice as high among pregnant Alaska Natives than pregnant non
      Natives. Overall, prevalence of smokeless tobacco use was four times higher among
      Alaska Natives than comparative state and national populations. CONCLUSION:
      Because this population has such high rates of tobacco use, it is important to
      public health that monitoring and educational programs be in place and that data
      specific to Alaska Natives be made available.

PMID- 9245668
TI  - Is screening for chronic obstructive pulmonary disease justified?
AB  - BACKGROUND: Many experts recommend spirometry to screen for chronic obstructive
      pulmonary disease (COPD) in asymptomatic patients; however, evidence for this
      recommendation has not been systematically reviewed. METHODS: We examined whether
      screening spirometry meets standard criteria for effective screening. We
      performed structured searches of MEDLINE, followed by a selective search of the
      CITATION index, to locate randomized trials of interventions for asymptomatic
      patients with COPD. In regard to smoking cessation, we included all controlled
      trials of smoking cessation programs that used spirometry. We also included all
      studies that assessed the ability of spirometry to predict successful smoking
      cessation by comparing baseline lung function in smokers who subsequently quit
      versus those who did not. RESULTS: With the exception of smoking cessation, all
      interventions for COPD have only been proven effective in symptomatic patients.
      Two studies found that multifaceted smoking cessation programs that included
      spirometry were efficacious. There was no effect in a third study that isolated
      the role of spirometry. Smokers with abnormal spirometric results are less likely
      than other smokers to quit over the ensuing year. CONCLUSIONS: There is no
      evidence that spirometry, as an isolated intervention, aids smoking cessation.

PMID- 9245669
TI  - Participation in a breast cancer screening program: influence of past behavior
      and determinants on future screening participation.
AB  - BACKGROUND: This study analyzed the relationship between past screening behavior,
      determinants, intention, and future screening participation in the Dutch national
      breast cancer screening program. METHODS: Participation at the first and second
      screening rounds was monitored. Furthermore, between the first and the second
      screening rounds, women received a questionnaire (response 58%, n = 395). The
      questionnaire was based on the ASE model, including attitude (consequences,
      anticipated regret, and moral obligation), social influence (support and
      modeling), and self-efficacy. Other distal variables assessed were previous
      screening behavior, evaluation of screening characteristics, and demographics.
      RESULTS: Participants at the second screening differed from nonparticipants on
      all ASE determinants. Stepwise multiple regression analyses showed that for
      previous participants and nonparticipants different ASE determinants and distal
      variables explained the variance in intention to participate in the next
      screening (30 to 45%). Logistic regression analyses showed that past behavior and
      intention (which mediated the effects of the ASE variables) were significant
      predictors of participation in the second screening. CONCLUSIONS: Differences
      between previous participants and nonparticipants in determinants of intention
      and future screening behavior can be used to improve participation and adherence
      to breast cancer screening.

PMID- 9245670
TI  - Variability in the timing of repeat screening mammography.
AB  - BACKGROUND: Although numerous studies have examined repeat mammography, they
      provide limited information about actual patterns of women's behavior over time.
      METHODS: In this study, 128 asymptomatic women ages 50 to 75 who had had their
      first mammograms 15 to 27 months previously were interviewed to determine rates
      of repeat mammography. Eighty-six of these women were HMO members; the remaining
      42 were nonmembers. RESULTS: In both subpopulations, repeat mammography rates
      were low among women interviewed less than 21 months after their first mammogram,
      but much higher among those interviewed 21 months or more afterward. CONCLUSIONS:
      These data suggest that waiting up to 2 years to have a second mammogram may be
      at least as common a choice as having it after 1 year. It is of particular
      interest that this was found in a population of HMO members who receive reminders
      and vouchers for free mammograms annually.

PMID- 9245671
TI  - Type A and Type B behaviors, work stressors, and social support at work.
AB  - BACKGROUND: How Type A personality is related to the stress process has been
      investigated. However, in the occupational health field, stressful aspects of the
      work environment for Type A or B workers have not been fully revealed. METHODS:
      In the present study, using signal detection analysis, we analyzed data
      concerning work stressors and social support (SS) at work among Japanese white
      collar workers (n = 560) and identified the respective aspects of work that are
      stressful for Type A and B workers. We also evaluated the interactions of SS at
      work and stressor variables among Type A and B workers, individually. RESULTS:
      Except for one significant predictor, i.e., being unable to learn new things at
      work, the significant predictors of mental stress were generally quite different
      for Type A and B workers. Specifically, SS from management was a cause of mental
      stress for certain groups of Type A workers. CONCLUSIONS: It was revealed that
      the stressful aspects of work environment varied markedly in accord with the Type
      A vs Type B personality status of the subjects. The results also implied that
      even support from management can be stressful for Type A workers who had heavy
      workloads. The present study used specific measures sensitive to individual
      stressors and identified specific subgroups with the same work stressors. The
      findings provide information that is useful for stress reduction intervention.

PMID- 9245672
TI  - Epidemiology of low total plasma cholesterol concentration among young adults:
      the CARDIA study. Coronary Artery Risk Development in Young Adults.
AB  - BACKGROUND: Data on stability of plasma total cholesterol levels and its
      determinants among young adults are lacking. Knowledge of factors associated with
      low levels of plasma total cholesterol during young adulthood may help clarify
      the nature of associations between hypocholesterolemia and health or illness.
      METHODS: Tracking of plasma total cholesterol was investigated using data from
      the baseline (1985-1986), Year 5 (1990-1991), and Year 7 (1992-1993) examinations
      of the Coronary Artery Risk Development in Young Adults Study. Lifestyle
      (including dietary), physiological, medical, and psychological correlates of
      plasma total cholesterol were examined cross-sectionally at baseline using ANCOVA
      and multivariate logistic regression. The attributes of participants with
      persistently low plasma total cholesterol level after 7 years (i.e., remaining
      below the 10th percentile of sex- and race-specific distributions) were also
      examined. RESULTS: The cohort in this analysis comprised 720 black men, 922 white
      men, 899 black women, and 944 white women who were between the ages of 18 and 30
      years at baseline. Between 44 and 52% of those with plasma total cholesterol
      levels below the 10th percentile remained below the same percentile 7 years
      later. Among black men, a difference of 1 SD in age [3.7 years; odds ratio (OR) =
      0.69; 95% CI = 0.52-0.91] and a difference of 1 SD in systolic blood pressure
      (10.5 mm Hg; OR = 0.73; 95% CI = 0.54-0.97) were independently associated with
      lower odds, respectively, of being in the lowest 10th percentile of the plasma
      total cholesterol distribution. Also among black men, current smoking and more
      calories from carbohydrates were associated with nonsignificantly higher odds of
      low total cholesterol level. Among white men, a 1 SD older age (3.4 years; OR =
      0.78; 95% CI = 0.61-1.00) and a 1 SD higher physical fitness (118 sec; OR = 1.41;
      95% CI = 1.09-1.82) predicted lower and higher odds, respectively, of low plasma
      total cholesterol. Among black women, a 1 SD difference in albumin (0.3 g/dL; OR
      = 0.80; 95% CI = 0.63-1.03) was related to lower odds of low plasma total
      cholesterol. Among white women, the factors independently associated with low
      plasma total cholesterol were body mass index (OR for a difference in 4.0 kg/m2 =
      0.73; 95% CI = 0.54-1.00) and gamma-glutamyl transferase (OR for an increase in
      9.6 IU/L = 0.41; 95% CI = 0.18-0.93). The independent predictive factors of
      stably low total cholesterol levels were age and uric acid among black men (both
      inversely related) and age, Framingham Type A Behavior (inversely), and calories
      from carbohydrates (positively related) among white men. CONCLUSION: Young adults
      with low plasma total cholesterol level have characteristics generally associated
      with good cardiovascular health. However, adverse attributes such as current
      cigarette smoking (notably among black men) may confound future associations
      between low total cholesterol and disease.

PMID- 9245674
TI  - Reducing ultraviolet radiation exposure in children.
AB  - BACKGROUND: Project SUNWISE evaluated the effectiveness of a multicomponent
      intervention in reducing children's ultraviolet radiation (UVR) exposure.
      METHODS: Across four YMCAs, 48 aquatics classes (N = 169 children, mean age = 7)
      were randomly assigned to either the intervention or the control condition. The 6
      week intervention included a UVR reduction curriculum presented at poolside by
      aquatics instructors and home-based activities for children and their parents.
      Outcome measures were (a) tanness-associated skin color dimensions assessed with
      a colorimeter, (b) specific daily solar protection behaviors of children as
      reported by parents, and (c) general solar protection behaviors. RESULTS:
      Controlling for intraclass clustering in all analyses, at posttest, no
      statistically significant between-group differences were found in tanness, daily
      solar protection scores, or general sunscreen use. The intervention group showed
      significantly greater general hat use relative to controls. CONCLUSIONS: The
      intervention failed to impact most of the outcome measures. Supplementing the
      behavior-focused intervention package with environmental supports may be
      warranted.

PMID- 9245673
TI  - Intake of nutrients related to cardiovascular disease risk among three groups of
      American Indians: the Strong Heart Dietary Study.
AB  - BACKGROUND: Although diet is implicated in the elevated rate of cardiovascular
      disease among some American Indian tribes, the dietary intakes of these
      individuals have not been described. The Strong Heart Dietary Study compared
      diets of 10 tribes in Arizona, Oklahoma, and the Dakotas to examine the possible
      contribution of diet to cardiovascular and other chronic diseases. METHODS:
      During 1988-1991, 892 people responded to a 24 hr diet recall questionnaire.
      Nutrient intake by study area, sex, and age group were compared by analysis of
      variance, and intakes were compared with nutrient intakes reported by
      participants in Phase 1 of the Third National Health and Nutrition Examination
      Survey and with dietary recommendations of the National Research Council, the
      American Heart Association, and the Healthy People 2000 objectives. RESULTS: The
      intake of energy and nutrients varied significantly by sex and age. Men consumed
      more energy, macronutrients, and sodium than did women (P < or = 0.001). Women's
      diets were denser in carbohydrate, beta-carotene, vitamin C, and vitamin E than
      were men's diets (P < or = 0.001). Younger participants consumed more energy,
      macronutrients, vitamin E, and sodium than did older participants (P < or =
      0.001). Older participants had diets denser in protein and beta-carotene than did
      younger participants (P < or = 0.001). Energy intake did not differ significantly
      by study area, but men in Arizona consumed more energy from carbohydrate and less
      energy from total fat than did men elsewhere (P < or = 0.01). Men and women in
      Arizona consumed more cholesterol and fiber than did other participants (P < or =
      0.01) and less of the antioxidant vitamins (P < or = 0.01). Participants in the
      Strong Heart Diet Study reported diets higher in fats and cholesterol than did
      participants in Phase 1 of the Third National Health and Nutrition Examination
      Survey. Few Strong Heart participants achieved dietary recommendations for the
      reduction of risk of chronic disease. CONCLUSIONS: Area differences in nutrient
      intake were observed, but most participants consumed diets associated with
      increased risk of heart disease and other chronic diseases. Women and older
      participants in general reported healthier nutrient intakes. Dietary intervention
      programs should educate American Indians about dietary modifications to reduce
      the risk of cardiovascular and other nutrition-related disorders.

PMID- 9245675
TI  - Trends in cardiovascular risk factors (1984-1993) in a Swiss region: results of
      three population surveys.
AB  - BACKGROUND: This study attempted to assess the time trends in lifestyle and
      cardiovascular risk factors in the Swiss region of Vaud-Fribourg (population
      784,000). METHODS: Three surveys (1984/1985, 1988/1989, and 1992/1993), based on
      independent representative samples (n = 3,300) of the population ages 25 to 74,
      were conducted within the framework of the international WHO-MONICA Project.
      RESULTS: The most favorable changes were observed in reported behaviors:
      increased physical activity in leisure time, healthier dietary habits (switch
      from unskimmed milk, butter, and meat to skimmed milk, margarine, and fish, with
      no change for fruits and vegetables), and lower prevalence of regular smoking
      among men (from 32 to 28%). Body mass index did not vary significantly, apart
      from an increase in the prevalence of obesity among men (from 11 to 15%). Total
      cholesterol varied only slightly, while the HDL cholesterol levels decreased
      steadily (from 1.37 to 1.19 mmol/L among men; from 1.59 to 1.51 among women).
      Average systolic blood pressure regressed among women (from 127.2 to 124.4 mm
      Hg), while the prevalence of untreated hypertension increased among older men.
      CONCLUSION: The self-reported changes in lifestyle were only partially reflected
      by favorable trends in objective measurements. Physical activity, even at
      moderate intensity, and consumption of fruits, vegetables, and fiber in general
      should be promoted.

PMID- 9245676
TI  - Trends in smoking by birth cohort for births between 1940 and 1975: a
      reconstructed cohort analysis of the 1990 Ontario Health Survey.
AB  - BACKGROUND: Smoking patterns have changed markedly over the past 70 years.
      Previous studies have shown that examination of smoking patterns within birth
      cohorts can identify important changes in tobacco adoption and cessation. This
      paper examines temporal trends in the prevalence of smoking and the age of
      smoking adoption and cessation for birth cohorts born between 1940 and 1975.
      METHODS: The underlying data were obtained from the Ontario Health Survey
      (conducted in 1990), which used a multistage stratified area sampling strategy to
      obtain interviews on 29,843 people age 12 or older. Self-reported smoking
      histories were used as the basis for a reconstructed cohort analysis of
      prevalence rates. A life events methodology was employed to examine the age at
      starting smoking and the time of smoking cessation. RESULTS: There has been a
      steady drop in peak smoking prevalence for men. This trend appears to be
      continuing among the most recent cohorts. However, for women, peak smoking
      prevalence increased until the 1960 birth cohort, after which time the peak
      prevalence has been dropping. Prevalence of smoking was much higher for men then
      for women among the earlier birth cohorts but, by the 1960 cohort, the prevalence
      for men and women was essentially the same. Examination of the age of smoking
      onset reveals that there was a statistically significant interaction between sex
      and birth cohort on the relative risk of starting smoking. The rate of smoking
      cessation has increased uniformly across all birth cohorts among both men and
      women. CONCLUSIONS: This study confirms recent trends in smoking reduction and
      provides no evidence to suggest a diminution of the effect. Trends in recent
      birth cohorts of women are encouraging. There is a clear need for public health
      initiatives directed at older children and teenagers in order to further reduce
      the onset of smoking. Efforts to prohibit advertising directed toward minors,
      sponsorship of sporting and cultural events, and the sale of tobacco to minors
      should receive high priority.

PMID- 9245677
TI  - Physician attitudes toward managing obesity: differences among six specialty
      groups.
AB  - BACKGROUND: The Healthy People 2000 report recommended that physicians more
      actively address obesity, but little is known about current attitudes and
      practices of physicians, particularly across specialty areas relevant to obesity
      as a medical risk factor. METHODS: A mail survey of 1,222 physicians from six
      specialties (family practice, internal medicine, gynecology, endocrinology,
      cardiology, and orthopedics) investigated beliefs, attitudes, and practices
      regarding obesity in relation to medical risk, management, and interest in
      training and other resources. RESULTS: Specialty groups shared high concern for
      the health risks of moderate and morbid obesity, but distinct attitudes and
      patterns of practice emerged. For example, family practitioners, internists, and
      endocrinologists reported treating obesity themselves in about 50% of obese
      patients, which correlated with reported use of more active treatment approaches
      (r = 0.62, P < 0.0001). Other groups reported intervening with 5 to 29% of
      patients, but expressed greater interest in making referrals. Physicians
      reporting "any specialty training related to ... obesity" ranged from 4.5% of
      family practitioners to 36.4% of endocrinologists. CONCLUSIONS: Physicians
      express high concern with management of obesity but variable interest in assuming
      this role themselves. Mild obesity may be particularly undertreated. Research is
      critically needed to assess effective physician roles in weight management and to
      support the development of physician guidelines.

PMID- 9245678
TI  - Body weight and risk of nonfatal acute myocardial infarction among women: a case
      control study from northern Italy.
AB  - BACKGROUND: The relationship between nonfatal acute myocardial infarction (AMI)
      and self-reported body weight and body mass index (BMI; Quetelet index, kg/m2)
      has been investigated. METHODS: A case-control study was conducted between 1983
      and 1992 in northern Italy on 432 women with nonfatal AMI and 867 controls in
      hospital for acute, noncardiovascular, nonneoplastic, nondigestive, non-hormone
      related conditions. Odds ratios (OR), with their 95% confidence intervals (CI),
      were computed by unconditional multiple logistic regression analysis, including
      terms for age, education, and smoking, plus history of selected diseases.
      RESULTS: Women with body weight and BMI in the highest quartile had an increased
      risk of AMI after allowance for age, education, and smoking status (OR 1.5, 95%
      CI 1.0 to 2.2, and OR 1.7, 95% CI 1.2 to 2.4, respectively). Compared with leaner
      women, the risk was higher among women with BMI above the median, in association
      with a history of diabetes (OR 5.2) or hyperlipidemia (OR 6.0). Hypertensive
      women had similar OR in the two strata of BMI (OR 5.1 and 4.8). The association
      of BMI with risk of AMI was apparently stronger among women younger than 50 years
      and among less educated women, but was similar among smokers and never smokers.
      CONCLUSIONS: The results of this study confirm that AMI among women is related to
      excess BMI, with a population attributable risk of 17%. The excess risk was
      substantial among overweight women with history of diabetes or hyperlipidemia,
      stressing the importance of controlling body weight among these women.

PMID- 9245679
TI  - Evaluation of a national Quit and Win contest: determinants for successful
      quitting.
AB  - BACKGROUND: Within the CINDI framework, a European "Quit and Win" contest was
      organized in 1994. In Finland the number of participants was 5,879 (0.6% of
      smokers). In the CINDI demonstration area, North Karelia (NK), the participants
      numbered 618 (2.0% of smokers). This study compared abstinence maintenance among
      the participants in NK with the rates found elsewhere in Finland and analyzed
      determinants for successful quitting. METHODS: A follow-up study was conducted 12
      months after the quit date with a sample of 2,114 participants. Response rates of
      67-68% were achieved (n = 1,419). The abstinence was assessed at 1, 6, and 12
      months. Two estimates are presented: (1) the proportion of abstainers among the
      respondents and (2) the proportion of abstainers among the sample, considering
      all nonrespondents smokers. The determinants for maintenance of smoking cessation
      were analyzed with logistic regression. RESULTS: Using the first estimate, the
      rates at 1/6/12 months were 75/36/28% in NK and 70/28/21% elsewhere (P < 0.01).
      Using the second estimate, the corresponding rates were 50/24/19% in NK and
      46/19/14% elsewhere. The most significant determinants for successful quitting
      were sex, age, marital status, level of withdrawal symptoms, previous quitting
      attempts, and support received. CONCLUSIONS: The recruitment of smokers and the
      maintained cessation were more successful in the demonstration area. The
      difference between areas was explained by differences in the combined
      professional and lay support and by the sex and age distributions.

PMID- 9245680
TI  - Unapproved use of high-dose combined pills in Japan: a community study on
      prevalence and health characteristics of the users.
AB  - BACKGROUND: Because of the ban on oral contraceptive use in Japan, only high-dose
      combined pills (HDCP), permitted as treatment for menstrual disorders, can be
      used as a contraceptive. We determined the prevalence of the use of such
      preparations in a community in Japan and assessed the health characteristics of
      the users. METHODS: A total of 18,435 female residents age 35 years and over in a
      city of Gifu Prefecture, Japan, responded in 1992 to a health questionnaire that
      included questions on the use of HDCP, lifestyle, and dietary habits. The
      response rate was 92%. RESULTS: The rates of current and past HDCP use were 1.3
      and 7.1%, respectively, among women ages 35-49 years, and 2.2% of the women had
      used HDCP for longer than any other method of contraception. Current HDCP users
      were more likely to be smokers. They had lower intakes of carotene, fiber, and
      vitamins C and E and a lower polyunsaturated/saturated fat ratio than never
      users. CONCLUSIONS: The prevalence of HDCP use was 1.3% among Japanese women ages
      35-49 years. Potential risk factors for cardiovascular diseases, such as smoking
      and a diet with lower intakes of antioxidants, were prevalent among current HDCP
      users.

PMID- 9245681
TI  - Correlates of changes in leisure time physical activity over 2 years: the Healthy
      Worker Project.
AB  - BACKGROUND: This study is the first to examine associations between concurrent
      changes in demongraphics, health behaviors, and physical activity in a free
      living cohort of adults. METHODS: Surveys were conducted at 32 worksites (n =
      3,672 workers) before and after a 2-year health promotion intervention.
      Associations between concurrent changes in sociodemographics, health, health
      behaviors, and physical activity were examined. Characteristics of individuals
      were also examined in four extreme physical activity change groupings:
      consistently very active, consistently very inactive, and changing from one
      extreme to the other over time. RESULTS: Among women, being married was
      associated with consistently low levels of physical activity, and increases in
      education were associated with increases in physical activity. Among both men and
      women, maintenance of single marital status was associated with increased
      physical activity levels, and increases in BMI were associated with decreases in
      physical activity. Increases in high-fat/calorie food intake were associated with
      increases in physical activity among men, but not among women. CONCLUSION: The
      observed associations indicate factors that may be important for understanding
      decreases in physical activity. The dynamic associations between changes in
      sociodemographics and physical activity demonstrate the need to examine changes
      in sociodemographics over time, rather than at only a single time point.

PMID- 9245682
TI  - Distributions of smokers by stage: international comparison and association with
      smoking prevalence.
AB  - OBJECTIVES: The goals of this study were to describe the distribution of smokers
      by stage of change in Geneva, Switzerland; to compare this result with
      distributions observed in other countries; and to assess whether, across samples
      from different countries, the stage distribution of current smokers was
      associated with the prevalence of smoking. METHODS: Two mailed surveys were
      conducted in Geneva in 1995-1996, in a representative sample of residents (n =
      742) and in a representative sample of university members (n = 2,270). A
      literature review produced seven studies describing the stage distribution in
      representative samples. RESULTS: In the Geneva population, 74% of smokers were in
      the precontemplation stage, 22% in contemplation, and 4% in preparation. In the
      university sample, the corresponding figures were 72, 20, and 8%. Our results
      were similar to other European samples, but less favorable than in American
      samples, where these distributions were typically 40, 40, and 20%, respectively.
      Across all samples, a low prevalence of smoking was associated with a more
      favorable stage distribution (r = 0.88, P = 0.002). CONCLUSIONS: Interventions in
      Europe need to take into account the large proportion of precontemplators
      repeatedly observed among smokers. A shift to the right of the distribution of
      current smokers across stages may help increase quit rates and thereby reduce
      smoking prevalence. This hypothesis should be tested in prospective intervention
      studies.

PMID- 9245683
TI  - Rationale, design, and baseline data for Commit to Quit: an exercise efficacy
      trial for smoking cessation among women.
AB  - BACKGROUND: The Commit to Quit trial was designed to address the methodological
      problems of prior studies that have examined the contribution of exercise to
      smoking cessation. METHODS: This paper provides an overview of the study design
      and describes the sample of women who participated in this trial (N = 281).
      Interrelationships among eating, exercise, and smoking behavior are examined.
      RESULTS: Subjects randomized into the study compared with the sample of women who
      completed the initial assessment but were not randomized were more likely to be
      white, to have at least a high school education, and to smoke fewer cigarettes
      per day. Overall, the most frequent ineligibility criteria were health-related
      issues and scheduling conflicts. On average, participants in this study smoked
      more cigarettes per day than national samples of women smokers. Significant
      interrelationships include the positive association of motivational readiness for
      quitting smoking and enhanced levels of dietary restraint and the positive
      association of motivational readiness for exercise adoption and high levels of
      weight concern. CONCLUSIONS: This study represents the first adequately powered
      randomized controlled clinical trial comparing the relative efficacy of a
      cognitive-behavioral smoking cessation treatment plus vigorous exercise with the
      same treatment plus contact control.

PMID- 9245684
TI  - Gene regulation by nuclear and cytoplasmic calcium signals.
AB  - Calcium entry into neuronal cells through N-methyl-D-aspartate (NMDA)-type
      glutamate receptors or L-type voltage-gated calcium channels is a key event in
      the control of gene expression following electrical activation. Calcium acts both
      in the cytoplasm and the nucleus to activate signalling pathways that stimulate
      gene expression through different DNA regulatory elements. Differential control
      of transcription by spatially distinct calcium signals provides a mechanism by
      which a single second messenger can generate diverse transcriptional responses.
      This may allow for stimulation-specific modulation of gene expression critical
      for adaptive changes in the nervous system.

PMID- 9245685
TI  - Autosomal recessive liver phosphorylase kinase deficiency caused by a novel
      splice-site mutation in the gene encoding the liver gamma subunit (PHKG2).
AB  - To facilitate mutation analysis of patients with an autosomal recessive form of
      liver phosphorylase kinase deficiency, the genomic structure of the gene encoding
      the testis/liver gamma subunit (PHKG2) was established. The gene consist of 10
      exons. The translation start site is located in exon 2. Analysis of DNA from two
      female siblings, affected with liver phosphorylase kinase deficiency, by exon
      specific amplification followed by direct sequencing, revealed a single donor
      splice site mutation in the PHKG2 gene, IVS4 + 1(g --> a). The mutation leads to
      the skipping of exon 4, which results in a frameshift, starting at nucleotide
      272, a premature stop codon after 32 additional amino acids, and subsequent loss
      of the catalytic site. It is concluded that deficiency of phosphorylase kinase in
      liver of the patients is caused by the IVS4 + 1(g --> a) mutation. In the
      patients described here, this genotype is associated with development of liver
      fibrosis.

PMID- 9245686
TI  - Characterization of voltage-dependent calcium influx in human erythrocytes by
      fura-2.
AB  - Thus far, the methods used to determine erythrocyte Ca2+ influx have not allowed
      the assessment of the kinetics of ion uptake. To overcome this drawback, we
      studied a new method, using the fluorescent Ca2+-chelator fura-2, which directly
      quantifies intracellular Ca2+ changes in human erythrocytes. This method has the
      advantage over previous techniques that it monitors continuously cellular Ca2+
      levels. The Ca2+ influx is modulated by cellular membrane potential in the
      presence of a transmembrane Ca2+ concentration gradient and exhibits a first slow
      increase of the intracellular Ca2+ concentration, followed, after the reachment
      of a threshold value of 125 +/- 13 nM Ca2+, by a faster increase until a plateau
      is reached. The influx rate is inhibited by dihydropyridines in the micromolar
      range. These findings support the hypothesis that erythrocyte Ca2+ influx is
      mediated by a carrier similar to the slow Ca2+ channels and is dependent on
      membrane depolarization.

PMID- 9245687
TI  - Evidence for participation of a calpain-like cysteine protease in cell cycle
      progression through late G1 phase.
AB  - Recent studies have demonstrated that cell-permeant protease inhibitors arrest
      human fibroblasts in late G1. The target for the inhibitors has been claimed to
      be either the proteasome, or a calpain-like cysteine protease activity. In the
      present investigation, the progression of serum-stimulated WI-38 fibroblasts into
      S-phase was partially inhibited by the cell-permeant general inhibitor of
      cysteine proteases, E64d, but not by its non-permeant anolog, E64c. Exposure of
      fibroblasts in late G1 to the proteasome inhibitor, lactacystin, produced only a
      modest inhibition of progression into S-phase, and did not influence the
      extensive inhibition produced by the calpain-selective inhibitor, ZLLY-DMK. ZLLnV
      CHO and ZLLL-CHO, which are reportedly selective for the proteasome, were less
      potent than ZLLY-DMK as inhibitors of S-phase progression. These results argue
      for the involvement of a calpain-like protease acting in late G1 to allow transit
      into S-phase.

PMID- 9245688
TI  - Molecular cloning and characterization of mammalian homologues of the Drosophila
      retinal degeneration B gene.
AB  - Null mutations in the retinal degeneration B gene (rdgB) in flies result in an
      activity-dependent retinal degeneration. Here we report the isolation of the
      mouse and human homologues of rdgB gene that are strongly expressed in brain and
      moderately expressed in other tissues. The deduced amino acid sequences encoding
      a 1244 a.a protein bear a 96% similarity between mouse and human and resemble the
      Drosophila rdgB, particularly in the phosphatidylinositol transfer domain at the
      N-terminus and in six putative transmembrane domains at the C-terminus.
      Immunoblots with antiserum raised against a bacterially expressed fragment of the
      mouse rdgB showed the band with a molecular weight of about 170 kDa.
      Interestingly, a burst of mouse rdgB expression occurs on 17th day of gestation,
      suggesting a crucial role of the gene product in brain development at this
      particular stage. A gene, mpt-1, encoding for mouse rdgB was mapped to the
      proximal end of chromosome 19, which is the same location as Mvb-1, a gene locus
      encoding the modifier of mouse vibrator mutation (mv).

PMID- 9245689
TI  - Sterol carrier protein X (SCPx) is a peroxisomal branched-chain beta-ketothiolase
      specifically reacting with 3-oxo-pristanoyl-CoA: a new, unique role for SCPx in
      branched-chain fatty acid metabolism in peroxisomes.
AB  - One of the most important functions of peroxisomes, at least in humans, is the
      beta-oxidation of a range of different fatty acids and fatty acid derivatives.
      Recent studies have shown that the enzymatic machinery required for the beta
      oxidations of these substrates, may be much more complex as originally thought.
      We now report that the conventional peroxisomal thiolase which has so far been
      thought to catalyze the thiolytic cleavage of the 3-oxoacyl-CoA esters of all
      fatty acids oxidized in peroxisomes, shows poor reactivity towards the 3-oxoacyl
      CoA esters of 2-methyl branched-chain fatty acids such as pristanic acid. Our
      data further show, that SCPx, a 58 kDa protein with both thiolase and sterol
      carrier protein activity but unknown function so far, readily reacts with 3
      oxopristanoyl-CoA. Taken together, our data show that SCPx plays a central role
      in branched chain fatty acid beta-oxidation in peroxisomes. This finding has
      major implications not only for the functional organization of the peroxisomal
      beta-oxidation system but also for studies dealing with the resolution of the
      underlying defect in patients with some defect in peroxisomal beta-oxidation.

PMID- 9245690
TI  - Evidence for myosin-binding phosphatase in heart myofibrils.
AB  - Protein phosphatase was partially purified from myofibrils of bovine heart by
      sequential column chromatographies. The purified protein phosphatase was
      immunologically identified as a delta isoform of PP1 (PP1delta). The myosin
      binding subunit (MBS) of myosin-binding phosphatase (MBP) in smooth muscle was co
      purified with PP1delta at each step of the sequential column chromatographies.
      The immunoprecipitation experiment using the polyclonal antibody to MBS showed
      that PP1delta associates with MBS in the purified phosphatase. In addition, the
      myosin-binding assay showed that the purified phosphatase has the characteristics
      of binding to cardiac myosin. These data strongly suggest that MBP, the
      holoenzyme composed of PP1delta and MBS, is expressed in heart myofibrils.

PMID- 9245691
TI  - DNA binding properties of the hfq gene product of Escherichia coli.
AB  - We found that plasmids isolated by alkaline-lysis method occasionally showed
      abnormal mobility on agarose gel electrophoresis. This abnormality was not
      detected after phenol extraction of plasmids, indicating that it was caused by
      proteinous factor(s). A 15-kDa protein was found in the plasmid preparations on
      SDS-PAGE. The sequence of eighteen N-terminal amino acid residues of the 15-kDa
      protein was identical with the host factor I (HF-I) encoded by the hfq gene at 95
      min on the Escherichia coli chromosome map, which is known to be required for
      bacteriophage Qbeta replication. The HF-I protein was purified and in vitro DNA
      binding experiment was carried out. HF-I bound to both supercoiled DNA and linear
      DNA and the binding of HF-I seemed to be sequence-nonspecific.

PMID- 9245692
TI  - B cell granule peptides affect human islet amyloid polypeptide (IAPP) fibril
      formation in vitro.
AB  - Islet amyloid polypeptide (IAPP) forms fibrils spontaneously. We examined whether
      other B cell granule peptides affect formation of beta-pleated sheet fibrils in
      vitro from human IAPP. Quantitative radioassay (radioactivity of soluble IAPP
      after adding 125I-IAPP) and thioflavine fluorescence spectroscopy showed that
      insulin, C-peptide, and pancreastatin inhibited fibril formation by 60-100% at
      ratio 100:1 (peptide:IAPP), whereas at 1:10 or 1:100, i.e., IAPP in excess, a
      potentiated IAPP fibril formation was induced by the peptides. Semi-quantitative
      analysis by electron microscopy yielded similar effects. Thus, spontaneous IAPP
      fibrillisation is influenced by other B cell secretory granule peptides in a
      molar ratio dependent manner.

PMID- 9245693
TI  - Reversal of heavy metal resistance in multidrug-resistant human KB carcinoma
      cells.
AB  - Human KB carcinoma C-A120 cells that express multidrug resistance-associated
      protein (MRP) were cross-resistant to trivalent and pentavalent antimonials and
      arsenicals. Intracellular glutathione (GSH) content was higher in C-A120 than its
      parental KB-3-1 cell line. Glutathione-S-transferase (GST) was similar in both
      cell lines. Depletion of cellular GSH by treatment of the cells with the
      inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), buthione sulfoximine
      (BSO), significantly increased the sensitivity of both KB-3-1 and C-A120 cells to
      heavy metals. A pyridine analog, PAK-104P, almost completely reversed the
      resistance to antimonials and arsenicals in C-A120 cells. BSO at 100 microM or
      PAK-104P at 10 microM enhanced the accumulation of antimony potassium tartrate in
      C-A120 cells to the level of that in KB-3-1 cells without the agents. PAK-104P
      inhibited the ATP-dependent efflux of antimony potassium tartrate. These findings
      suggest that MRP transports antimony conjugated with GSH ATP-dependently outside
      the cells and PAK-104P inhibits the transporting activity of MRP.

PMID- 9245694
TI  - Peroxynitrite scavenging by flavonoids.
AB  - The peroxynitrite scavenging activity of a series of structurally related
      flavonoids was tested. It was found that flavonoids are excellent scavengers of
      peroxynitrite. Compared to the known peroxynitrite scavenger ebselen, the most
      active flavonoids proved to be 10 times more effective. Indications were found
      that the catechol group (ring B) and the hydroxyl group at position 3 give the
      highest contribution to the peroxynitrite scavenging effect. The peroxynitrite
      scavenging is discussed in relation to the beneficial effect of flavonoid intake
      on the incidence of coronary heart disease.

PMID- 9245695
TI  - Staurosporine induces telophase arrest and apoptosis blocking mitosis exit in
      human Chang liver cells.
AB  - Staurosporine is a protein kinase inhibitor that is known to block G1/S and G2/M
      cell cycle transitions, resulting in the accumulation of G1 or G2 interphase
      cells, depending on the applied dosage. It is, however, not known to block
      mitosis (M-phase) progression. We show here that a 15 min prepulse with 500 nM
      staurosporine had caused mitotic cell arrest in human Chang liver cells,
      accumulating telophase cells distinguished by their doublet nuclei and
      cytokinetic constrictions. The arrested telophase cells perished by apoptosis.
      Telophase-specific cell cycle arrest and apoptosis are novel. Staurosporine
      targeting cytokinesis could provide insights into late mitosis where control
      mechanisms remain largely unknown.

PMID- 9245696
TI  - MAP kinase activation by cyclosporine A.
AB  - Short treatment of HeLa cells with cyclosporine A led to the activation in the
      crude cell extracts of a MAP kinase-like activity. Fractionation by
      chromatography on a Mono Q column allowed the separation of two activities co
      eluting with the MAP kinases ERK1 and ERK2. The activation of these two MAP
      kinases was demonstrated in Western Blotting by the appearance, after CsA
      treatment, of two new slowly migrating forms on SDS electrophoretic gels. A
      similar activation was also obtained in renal epithelial BSC-1 cells and 3T3
      fibroblasts. MAP kinase activation might result from a perturbation of calcium
      homeostasis induced by CsA treatment.

PMID- 9245697
TI  - Interaction of human angiogenin with copper modulates angiogenin binding to
      endothelial cells.
AB  - Angiogenin is a potent inducer of blood-vessel formation with ribonucleolytic
      activity. Angiogenin binds to high affinity endothelial cell receptors and with
      lower affinity to extracellular matrix components. Here we report the effect of
      copper and zinc on these interactions. There was a 4.3-fold increase in
      angiogenin binding to calf pulmonary artery endothelial cells in the presence of
      Cu2+ in vitro. A 3.8-fold increase was observed with Zn2+, whereas Ni2+, Co2+, or
      Li+ had no effect. Specific angiogenin binding to the lower affinity matrix sites
      was increased by 2.7- and 1.9-fold in the presence of Cu2+ and Zn2+ respectively.
      Metal ion affinity chromatography and atomic absorption spectrometry were used to
      show the direct interaction of angiogenin with copper and zinc ions. Angiogenin
      bound 2.4 mol of copper per mole of protein. We suggest that copper, a modulator
      of angiogenesis in vivo, may be involved in the regulation of the biological
      activity of angiogenin.

PMID- 9245698
TI  - Analysis of expressed sequence tags (ESTs) of the parasitic protozoa Entamoeba
      histolytica.
AB  - A directional cDNA library constructed from mRNA of the trophozoite of Entamoeba
      histolytica HM-1:IMSS strain was used for the generation of expressed sequence
      tags (ESTs). From 5' ends of the distinct cDNA clones, 105 ESTs were obtained. Of
      these, 30 clones (29%) were previously known E. histolytica genes. Forty-five
      clones (42%) had matches with entries for other organisms in the databases. These
      new E. histolytica genes constituted a broad range of transcripts distributed
      among cytoplasmic structural and regulatory proteins, enzymes, nuclear and other
      proteins, and proteins of unknown function. Thirty clones (29%) had no
      significant database matches and thus potentially represent E. histolytica
      specific genes. These data of E. histolytica genes identified by nucleotide
      sequencing indicate the value of the adoption of genome sequencing strategies for
      the rapid increase in knowledge of organisms causing dysentery and liver abscess.

PMID- 9245699
TI  - Proximal 5'-flanking sequence of the human gamma-glutamylcysteine synthetase
      heavy subunit gene is involved in cisplatin-induced transcriptional up-regulation
      in a lung cancer cell line SBC-3.
AB  - The contribution of the 5'-flanking sequence of the human gamma-glutamylcysteine
      synthetase heavy subunit (gamma-GCSh) gene to cisplatin-induced transcriptional
      up-regulation was studied using various human growth hormone reporter constructs
      which were transfected to a human lung cancer cell line SBC-3. Cisplatin at the
      concentration of 3 microM increased the transcriptional activity of the longest
      sequence from -1,413 to +91 bp of the gamma-GCSh gene to 246% of that in non
      exposed cells. The distal sequence from -1,413 to -193 bp was shown to negatively
      regulate transcriptional activity in both cisplatin-exposed and non-exposed cells
      using deletion and thymidine kinase (TK) promoter-linked constructs. Cisplatin
      increased the transcriptional activity of the proximal GC-rich sequence from -192
      to +91 bp to 340%, of which magnitude was the maximum among deletion constructs.
      A deletion from -108 to -28 bp, or +34 to +91 bp significantly decreased
      cisplatin-induced increases in transcriptional activity from 258 to 105%, or 340
      to 160%, respectively. When the sequence from -108 to -22 bp, or +26 to +91 bp
      was linked to the heterologous TK promoter, cisplatin increased the
      transcriptional activity to 171 or 181%, respectively, from that of 128 or 137%,
      respectively, in non-exposed cells. These findings indicate that the proximal
      sequence from -192 to +91 bp of the gamma-GCSh gene, especially from -108 to -28
      bp, and +34 to +91 bp, is involved in cisplatin-induced transcriptional up
      regulation in SBC-3 cells.

PMID- 9245700
TI  - The angiotensin-II receptor antagonist, losartan, inhibits LDL lipid peroxidation
      and atherosclerosis in apolipoprotein E-deficient mice.
AB  - The potential antiatherogenic actions of the angiotensin II receptor antagonist,
      losartan were investigated in apolipoprotein (apo) E deficient mice, an animal
      model with severe hypercholesterolemia and extensive atherosclerosis. In these
      animals accelerated atherosclerosis is associated with increased lipid
      peroxidation which may play a crucial role in the build up of the atherosclerotic
      lesions. Administration of losartan (25mg/kg/d) to the apo E deficient mice for a
      3-month period increased the plasma renin activity 3.5-fold compared to the
      placebo group. Losartan increased the resistance of LDL to CuSO4-induced
      oxidative modification as shown by a significant reduction in the LDL content of
      malondialdehyde by 55% compared to placebo, as well as by the prolongation of the
      lag time required for LDL oxidation, from 60 min in the placebo-treated mice to
      more than 140 min in the losartan-treated mice. Losartan reduced significantly
      the mean atherosclerotic lesion area by 80% compared to the placebo group. We
      conclude that losartan inhibits LDL lipid peroxidation in the apo E deficient
      mice and this effect may have an important role in the attenuation of the
      accelerated atherosclerosis.

PMID- 9245701
TI  - Modulation of protein kinase C and cAMP-dependent protein kinase by delta-opioid.
AB  - Modulation of protein kinase C (PKC) and cAMP-dependent protein kinase (PKA)
      activities by delta-opioid receptor specific agonist [D-Pen2, D-Pen5]-enkephalin
      (DPDPE) was investigated in neuroblastoma x glioma hybrid NG 108-15 cells. DPDPE
      activated PKC in a dose-dependent manner, with the maximal response at 5 min. The
      DPDPE-stimulated PKC activation could be blocked by naltrindole. The activation
      of PKC by DPDPE was dependent on Ca2+ and was inhibited by chelerythrine chloride
      (10 microM), but not by H89 (1 microM). Pretreatment of NG 108-15 cells with
      pertussis toxin (100 ng/ml for 24 h) completely abolished DPDPE-stimulated PKC
      activation. In contrast to the result from the acute treatment with DPDPE, which
      had no significant effect on PKA activity, chronic treatment of DPDPE (1 microM
      for 24 h) increased PKA activity, but reduced the basal activity of PKC. These
      results demonstrated that DPDPE differentially modulated PKC and PKA activities
      via a receptor-mediated, PTX sensitive pathway.

PMID- 9245702
TI  - Molecular structure of the mouse CCK-A receptor gene.
AB  - We have cloned the mouse CCK-A receptor gene (Cckar), determined its nucleotide
      sequence, and analyzed its expression. The receptor protein is encoded in five
      exons distributed over 9 kb of genomic DNA. Intron/exon borders were determined
      by comparing the genomic nucleotide sequence with the mouse cDNA sequence
      obtained by reverse transcriptase polymerase chain reaction. RNase protection
      analysis of Cckar transcripts revealed the presence of a splice acceptor site 200
      bp upstream of the translational start codon, indicating that the promoter is
      associated with a non-translated exon at an upstream site. The second coding exon
      contains a rarely used alternative splice site that would result in the
      production of a truncated, 48 amino acid protein. Cckar is widely expressed in
      the gastrointestinal system (pancreas, gallbladder, intestine, colon and
      stomach), as well as in brain and kidney.

PMID- 9245704
TI  - Identification of two homologous cytochrome b5s in rat brain.
AB  - Two kinds of PCR products were isolated from adult rat brain. The smaller product
      matched up to liver b5 mRNA completely. However, the larger one contained an
      additional 58 bp inserted between amino acids 96 and 97. This insertion was
      previously unknown and corresponded to in-frame codons for his-ser-ala-leu and
      the early stop. It is assumed that these two forms arise from a primary
      transcript by differential mRNA processing. This finding strongly suggests that
      there are two homologous b5s expressed in rat brain.

PMID- 9245703
TI  - Inhibition of DNA unwinding and ATPase activities of human DNA helicase II by
      chemotherapeutic agents.
AB  - DNA helicases catalyze the unwinding of duplex DNA and thus play important roles
      in the processing of DNA, little is known about the effects of various cytotoxic
      or antitumor chemotherapeutic agents on purified human DNA helicases. We have
      determined the effect of actinomycin C1, VP-16, camptothecin, ethidium bromide,
      ellipticine, nogalamycin, novobiocin, genistein, m-AMSA, aphidicolin and
      daunorubicin on the enzymatic activities of purified human DNA helicase II which
      was identified as Ku autoantigen. Ku contains DNA helicase, ATPase and DNA end
      binding activities. Our data have shown that out of several chemotherapeutic
      agents tested ethidium bromide, actinomycin C1, daunorubicin and nogalamycin were
      inhibitors of DNA unwinding activity of human DNA helicase II with ID50 values of
      8.44 microM, 11.68 microM, 6.23 microM and 0.42 microM respectively. These
      inhibitors also inhibited the ATPase activity but not the DNA binding activity of
      this helicase. This inhibition could be due to binding of these drugs to DNA,
      thereby impeding the movement of the helicase for unwinding action which may be
      their most important pharmacological function against cancer cells.

PMID- 9245705
TI  - The consequences of a mild respiratory chain deficiency on substrate competitive
      oxidation in human mitochondria.
AB  - The competition between the respiratory substrates to gain access simultaneously
      to the respiratory chain depends on the dehydrogenase activity, the mitochondrial
      ubiquinone pool, and the oxidizing activity of the cytochrome segment. By
      studying the co-oxidation of NADH and succinate by control human liver
      homogenates, we found that a change in the balance between respiratory chain
      complex activities may affect significantly the ability of the mitochondria to
      oxidize one or the other substrate. Accordingly, in the particular case of a
      patient presenting with a partial complex I and IV deficiency, we observed a
      strongly reduced ability to oxidize NADH in the presence of succinate. It
      therefore appeared that even a slight imbalance between respiratory chain enzyme
      activities may result in a full blockade of a given substrate oxidation.

PMID- 9245706
TI  - Treadmill running increases phosphatidylinostol 3-kinase activity in rat skeletal
      muscle.
AB  - Exercise has been shown to increase insulin-stimulated skeletal muscle glucose
      transport. Activation of phosphatidylinostol 3-kinase (PI 3-kinase) is required
      for insulin to stimulate glucose transport. The present study was designed to
      investigate whether treadmill running (60 min, 8% grade, 30 m/min) augments
      insulin-stimulated activation of PI 3-kinase. Insulin dramatically increased
      insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (p < 0.05).
      Treadmill running did not induce IRS-1 tyrosine phosphorylation, not did it alter
      insulin-stimulated IRS-1 tyrosine phosphorylation. Insulin increased PI 3-kinase
      activity by 3.0-fold (over basal activity) in white muscle and 5.2-fold in red
      muscle (p < 0.05). Exercise did not alter basal PI 3-kinase activity in either
      white or red muscle. However, in response to exercise, insulin-stimulated PI 3
      kinase activity was significantly increased in both muscle fibers (p < 0.05).
      These results suggest that increased insulin responsiveness induced by exercise
      may be due, in part, to enhanced insulin-stimulated PI 3-kinase activity.

PMID- 9245707
TI  - Suppression of tumor growth with recombinant murine angiostatin.
AB  - Angiostatin, a 38 kDa internal fragment of plasminogen, is an antiangiogenic
      endothelial cell inhibitor. It regresses several primary and metastatic tumors in
      mice. To produce recombinant angiostatin for further structural and functional
      studies, the mouse angiostatin gene preceded by a sequence including a signal
      peptide of plasminogen was introduced into baculovirus. Recombinant murine
      angiostatin was purified from the culture medium of angiostatin baculovirus
      infected insect cells (yield = 1 mg/liter) with a single-step of lysine-Sepharose
      chromatography. The angiostatin baculovirus-infected insect cells expressed and
      secreted a 52 kDa polypeptide that demonstrated all of the biological activities
      of angiostatin. A partial amino acid sequence of the NH2-terminus of the secreted
      protein revealed that the signal peptide was recognized and properly cleaved in
      insect cells. The recombinant murine angiostatin potently inhibited the
      proliferation of bovine capillary endothelial cells in vitro (half maximal
      inhibition = 50 ng/ml) and suppressed the growth of primary Lewis lung carcinoma
      in vivo (6 mg/kg/day, T/C = 0.08).

PMID- 9245708
TI  - Upstream NF-kappaB site is required for the maximal expression of mouse inducible
      nitric oxide synthase gene in interferon-gamma plus lipopolysaccharide-induced
      RAW 264.7 macrophages.
AB  - Transient transfection assays with various deletion mutants of the mouse
      inducible nitric oxide synthase (iNOS) promoter linked to a CAT reporter gene
      demonstrated that, besides the downstream NF-kappaB site, the region from -973 to
      -925 which contains a potential binding site for NF-kappaB (upstream NF-kappaB
      site) also mediated lipopolysaccharide (LPS)-inducibility in mouse macrophage
      cell line RAW 264.7. Site-specific mutation of three conserved nucleotides within
      the upstream NF-kappaB site abolished additional induction by LPS as well as
      maximal expression of iNOS by IFN-gamma plus LPS. In contrast, site-specific
      mutation of the downstream NF-kappaB site caused almost all reduction in
      expression of the reporter gene by LPS or LPS plus IFN-gamma. Electrophoretic
      mobility shift assays with the two NF-kappaB sites showed LPS-induced NF-kappaB
      binding to both probes and its higher affinity to the upstream NF-kappaB site.
      Taken together, these suggest that the upstream NF-kappaB site having enhancer
      function, besides the downstream NF-kappaB site as a core promoter, is essential
      for maximal expression of the iNOS gene.

PMID- 9245709
TI  - Three unrelated perturbations similarly uncouple fluid, bulk-membrane, and
      receptor endosomal flow in rat fetal fibroblasts.
AB  - We have compared the effects of three perturbations (treatment with 2 microM
      monensin, potassium depletion, and incubation in 0.35 M NaCl) on recycling of
      internalized fluid-phase, bulk-membrane, and receptor-mediated tracers in rat
      fetal fibroblasts. Monensin accelerated 2-fold the regurgitation of the fluid
      phase tracer horseradish peroxidase (HRP), as previously described in these cells
      after potassium depletion or upon incubation in hypertonic medium (1), and all
      treatments severely inhibited transfer of HRP from endosomes to lysosomes. In
      comparison, recycling of (6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]hexanoyl
      glucosylsphingosine (C6-NBD-GlcCer), a fluorescent lipid used as a bulk-membrane
      probe, was not significantly affected while transferrin recycling was slowed down
      2-fold. The striking similarities of these unrelated perturbations in their
      distinct effects on fluid, bulk-membrane, and receptor addressing point to common
      targets regulating these mechanisms.

PMID- 9245710
TI  - Modulation of insulin secretion and glycemia by selective inhibition of cyclic
      AMP phosphodiesterase III.
AB  - The effects of selective inhibition of cyclic AMP phosphodiesterase type III on
      insulin and glucose levels during an oral glucose challenge were evaluated in
      obese, diabetic ob/ob mice and in lean, non-diabetic littermates using the
      selective inhibitor, milrinone. Oral administration of milrinone increased plasma
      insulin levels both in ob/ob and in lean mice. Glucose tolerance was improved in
      lean, but not in ob/ob mice, where glucose levels were increased by milrinone
      treatment. In isolated hepatocytes from normal rats incubation with 200 microM
      milrinone caused a 30% increase in glucose release with a corresponding depletion
      of glycogen stores. Stimulation of isolated rat adipocytes with 200 microM
      milrinone increased glycerol release 7-fold. We conclude that selective
      inhibitors of cyclic AMP phosphodiesterase III are effective insulin
      secretagogues, but their therapeutic utility may be limited by their concurrent
      stimulation of lipolysis and hepatic glucose output.

PMID- 9245711
TI  - Structural motif and characteristics of the extracellular domain of P2X
      receptors.
AB  - Seven sequences of the proteins recently cloned from rat tissues and identified
      as P2X receptors are examined. Their putative transmembrane and extracellular
      domains and the most probable locations of disulphide bridges are discussed. Some
      surface accessible regions are identified and the structure of the putative ATP
      binding domain is discussed in the light of known selectivities and physiological
      characteristics of individual P2X subunits. The summarised information and the
      theoretical considerations regarding the protein structure of P2X receptors have
      been used to select amino acid sequences for raising antibodies against the P2X1
      receptor subunit. Initial results suggest that, in rat brainstem, P2X1 receptor
      subunits are found on a distinct subpopulation of neuronal perikarya in
      distributions consistent with distributions of known alpha,beta-methylene-ATP
      autoradiography and physiological effects of purinoceptor activation.

PMID- 9245712
TI  - Isolation of 1-methyl-1,2,3,4-tetrahydroisoquinoline-synthesizing enzyme from rat
      brain: a possible Parkinson's disease-preventing enzyme.
AB  - An endogenous parkinsonism-preventing substance, 1-methyl-1,2,3,4
      tetrahydroisoquinoline, is enzymatically formed from 2-phenethylamine and
      pyruvate in rat brain. The enzyme involved was localized in the mitochondrial
      synaptosomal fraction of rat brain, solubilized by treatment with sodium
      deoxycholate. In order to purify the enzyme, gel filtration was carried out. This
      enzyme may be important in the pathogenesis of Parkinson's disease.

PMID- 9245713
TI  - Characterization of posttranslational modifications of human A33 antigen, a novel
      palmitoylated surface glycoprotein of human gastrointestinal epithelium.
AB  - Monoclonal antibody (mAb) A33 recognizes a differentiation antigen (A33)
      expressed in normal human gastrointestinal epithelium and in 95% of human colon
      cancers. Murine mAb A33 shows specific targeting of colon cancer in humans and a
      humanized A33 antibody is currently being evaluated in the clinic. The cDNA for
      the human A33 antigen has recently been cloned, and sequence comparison indicated
      that the A33 antigen is a novel human cell surface molecule of the immunoglobulin
      superfamily. Because mAb A33 recognizes a conformational epitope, only a partial
      characterization of the A33 antigen has been carried out to date. In this report
      we show that the A33 antigen is (I) N-glycosylated, containing approximately 8 K
      of N-linked carbohydrate and there is no evidence for O-glycosylation,
      sialylation or glycophosphatidylinositol, and (ii) S-acylated in vitro,
      incorporating [3H] palmitic acid linked through a hydroxylamine-sensitive
      thioester bond. The S-palmitoylation may be involved in regulating the
      internalization process initiated by binding of mAb A33 to cell surface A33
      antigen.

PMID- 9245714
TI  - Tyrosine phosphorylation of insulin receptor substrate-1 and activation of the PI
      3-kinase pathway by glycine-extended gastrin precursors.
AB  - Glycine-extended gastrin precursors (G-Gly) were considered as processing
      intermediates devoid of biological activity. However, we have recently identified
      selective receptors for G-Gly which mediate the proliferative effects of this
      precursor. Little is known about the signaling pathways activated by G-Gly. In
      the present study, we demonstrate that PI-3-kinase is rapidly and transiently
      activated by G-Gly. We also observed a rapid increase in the tyrosine
      phosphorylation of IRS-1 and an activation of the PI-3-kinase in anti-IRS-1
      immunoprecipitates, suggesting that PI-3-kinase may be activated by association
      with tyrosine phosphorylated IRS-1. We also demonstrated that gastrin precursors
      activate the serine/threonine kinase, p70 kDa S6 kinase (p70S6K), through a
      wortmannin sensitive pathway.

PMID- 9245715
TI  - Expression of the POU transcription factor Brn-5 inhibits proliferation of NG108
      15 cells.
AB  - The POU domain transcription factors are a subgroup of homeodomain proteins that
      appears to control cellular phenotypes. The expression of the POU protein Brn-5
      occurs selectively in postmitotic CNS neurons. Ectopic expression of Brn-5 in
      dividing NG108-15 cells reduces the level of RNA encoding the proliferating cell
      nuclear antigen (PCNA). This ectopic expression also inhibits DNA synthesis as
      measured by the incorporation of bromodeoxyuridine (BrdU). Thus, Brn-5 may
      inhibit the continued proliferation of these cells. A potential function of Brn-5
      may be to suppress the action of proliferative signals in postmitotic neurons and
      thus prevents them from reentering the cell cycle.

PMID- 9245716
TI  - Up-regulation of Syk activity during HL60 cell differentiation into granulocyte
      but not into monocyte/macrophage-lineage.
AB  - Following induction of cell differentiation in vitro, an increase in Syk activity
      was observed only in HL60 cells differentiation into granulocytes induced by all
      trans retinoic acid (RA) but not into macrophages induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA) or monocytes induced by sodium butyrate.
      This elevation of Syk activity was the specific increase in kinase activity
      because the Syk amount was not altered before and after differentiation. Anti
      phosphotyrosine blot revealed that tyrosine phosphorylation of Syk was
      significantly increased as the function of induction time by RA, but not by TPA
      and sodium butyrate, suggesting that tyrosine phosphorylation might account for
      Syk activation. More importantly, Syk tyrosine phosphorylation and Syk activity
      were not altered in U937 and K562 cells which undergo monocyte differentiation
      and no differentiation, respectively, in response to RA induction. Taken
      together, Syk might exert a unique role in directing HL60 cells toward
      granulocyte differentiation.

PMID- 9245717
TI  - Phosphorylation of calmodulin by myosin light chain kinase is altered by exchange
      or duplication of EF-hand pairs.
AB  - We have previously demonstrated that under certain conditions, myosin light chain
      kinase can phosphorylate its activator, calmodulin. In this study we show that
      myosin light chain kinase from chicken gizzard can phosphorylate recombinant
      calmodulins in which the EF-hand pairs (Ca2+-binding domains) are duplicated or
      exchanged. Three mutants were used CaMNN (the amino-terminal EF-hand pair is
      duplicated), CaMCC (the carboxy-terminal EF-hand pair is duplicated) and CaMCN
      (the carboxy- and amino-terminal EF-hand pairs are switched). Myosin light chain
      kinase phosphorylated CaMNN and CaMCN to a greater extent than wild-type CaM but
      did not phosphorylate CaMCC. While CaMCC is a competitive inhibitor of myosin
      light chain kinase-catalyzed phosphorylation of myosin light chains, it did not
      prevent the phosphorylation of native calmodulin under the conditions employed in
      these studies. These data suggest that, although the carboxy- and amino-terminal
      EF-hand pairs are similar, their orientation can be distinguished by chicken
      gizzard myosin light chain kinase.

PMID- 9245718
TI  - Endothelial nitric oxide synthase gene transfer inhibits platelet-derived growth
      factor-BB stimulated focal adhesion kinase and paxillin phosphorylation in
      vascular smooth muscle cells.
AB  - Stimulation of smooth muscle (VSM) cells of guinea pig coronary artery by
      platelet-derived growth factor (PDGF)-BB retards paxillin mobility (mobility
      shift) in SDS-PAGE in a time-dependent manner. This mobility shift may be due to
      tyrosine phosphorylation of paxillin. eNOS gene transfer by replication deficient
      recombinant adenovirus vector AD5/RSVeNOS in VSM cells inhibited PDGF-BB
      stimulated mobility shift and tyrosine phosphorylation of paxillin.
      Concomitantly, tyrosine phosphorylation of focal adhesion kinase (FAK) was also
      inhibited. The inhibition of paxillin and FAK tyrosine phosphorylation did not
      affect stress fiber and focal adhesion formation. Considering the importance of
      FAK and paxillin in cell migration and proliferation, these results suggest that
      the FAK-paxillin pathway is a target for NO action to inhibit VSM cell migration
      and proliferation.

PMID- 9245719
TI  - Advanced glycation end products induce expression of vascular endothelial growth
      factor by retinal Muller cells.
AB  - Recent studies have suggested that advanced glycation end products (AGEs) are
      involved in the development of diabetic complications. To assess the pathogenic
      role of AGEs and vascular endothelial growth factor (VEGF) in the development of
      retinal neovascularization in diabetic retinopathy, we investigated the effect of
      AGEs on induction of VEGF by retinal Muller cells and measured AGE and VEGF
      concentrations in the vitreous of patients with proliferative diabetic
      retinopathy (PDR) and nondiabetic patients. The expression of VEGF mRNA and the
      production of VEGF protein by cultured Muller cells were enhanced by the presence
      of AGEs. The vitreous concentrations of AGEs and VEGF were both elevated in
      patients with PDR compared with patients without diabetes (P < 0.01). There was a
      moderate positive correlation between the levels of crossline and VEGF (r=0.698,
      P < 0.01). Elevation of AGEs in the vitreous may promote intraocular
      neovascularization in diabetic retinopathy through production of VEGF from Muller
      cells.

PMID- 9245720
TI  - Molecular cloning and expression of 56-58 KD antigen associated with transplant
      coronary artery disease.
AB  - High circulating levels of anti-endothelial antibodies have been reported in
      patients with accelerated transplant coronary artery disease (TxCAD); however,
      the nature or characteristics of the antigen to which these antibodies bind in
      vivo remain unclear. To identify the antigen, a human endothelial cell cDNA
      expression library was constructed in lambdaZAP and immuno-screened with serum
      containing a high titre of anti-endothelial antibodies. Nucleotide sequence of
      cloned cDNA inserts and GenBank database searches revealed a 94% identity in a 35
      bp overlap to the human vimentin gene. The cloned antigen fusion protein co
      migrated with human vimentin of molecular mass 56-58 KD in SDS-PAGE and exhibited
      immunoreactivity towards monoclonal and polyclonal anti-human vimentin
      antibodies. These results suggest that the 56-58 KD antigen associated with
      accelerated TxCAD is vimentin (or a vimentin-like protein), a cytoskeletal
      protein present in cells of the blood vessel walls.

PMID- 9245721
TI  - Differential expression of Rab3 isoforms during differentiation of pancreatic
      acinar cell line AR42J.
AB  - Evidence is accumulating that low molecular weight GTPases of the Rab3 subfamily
      regulate exocytosis in secretory cells. The different isoforms of Rab3 (Rab3AD)
      probably have opposite roles in secretory processes. In the present study we have
      investigated differentiation-dependent expression of Rab3 isoforms in the
      pancreatic acinar carcinoma cell line AR42J. The data show that AR42J cells
      express all four different isoforms of Rab3. Dexamethasone treatment, which
      increases the number of secretory granules and secretagogue-induced exocytosis
      several-fold, was accompanied by down-regulation of Rab3A, Rab3C, and Rab3D mRNA,
      whereas Rab3B mRNA and Rab3 protein were found up-regulated at the mRNA and
      protein level, suggesting that Rab3B might be involved in the secretory function
      of AR42J cells.

PMID- 9245722
TI  - Natural occurrence of 2'-phospho-cyclic ADP ribose in mammalian tissues.
AB  - 2'-Phospho-cyclic ADP-ribose (P-cADPR) is a newly identified Ca2+-mobilizing
      agent derived from NADP that stimulates intracellular Ca2+ release by a mechanism
      distinct from inositol 1, 4, 5-trisphosphate. In this report, we show that P
      cADPR is an endogenous metabolite in bovine tissues with basal levels ranging
      from 17.6 to 89.5 fmol/mg protein. The natural occurrence of this Ca2+-mobilizing
      nucleotide provides a potential link between NADP(H) metabolism and regulation of
      Ca2+ homeostasis.

PMID- 9245723
TI  - Purification and molecular cloning of the group II chaperonin from the
      acidothermophilic archaeon, Sulfolobus sp. strain 7.
AB  - To elucidate the structure and functional mechanism of the group II chaperonin,
      molecular cloning of the gene for and purification of the group II chaperonin
      from the thermoacidophilic archaeon Sulfolobus sp. strain 7 were performed. The
      purified Sulfolobus chaperonin exhibited weak ATPase activity and arrested the
      spontaneous refolding of the thermophilic lactate dehydrogenase. However, the
      refolding could not be resumed by addition of ATP. The chaperonin consists of two
      kinds of subunits, alpha and beta, the deduced amino acid sequences of which were
      highly homologous to those of TF56 and TF55 from Sulfolobus shibatae,
      respectively.

PMID- 9245724
TI  - Abnormalities of sensory and memory functions in mice lacking Bsg gene.
AB  - Basigin is a highly glycosylated transmembrane protein belonging to the
      immunoglobulin superfamily. We used mutant mice lacking the basigin gene (Bsg) to
      investigate its involvement in learning and memory. Mutations were generated by
      the gene targeting method. Various kinds of learning and memory tasks were
      performed in mutant, hetero and wild type mice. The mutant mice showed worse
      performance than the wild and hetero mice in the Y-maze task, which assesses
      short-term memory, and in the water finding task, which examines latent learning,
      without any motor dysfunction. Moreover, the mutant mice showed less acclimation
      in the habituation task compared with the wild-type mice. The mutant mice were
      also more sensitive to electric foot-shock. These findings are consistent with
      the expression profile of basigin in the central nervous system. Thus, basigin
      may play an important role in learning and memory as well as in the sensory
      functions.

PMID- 9245725
TI  - Selective loading of Rhod 2 into mitochondria shows mitochondrial Ca2+ transients
      during the contractile cycle in adult rabbit cardiac myocytes.
AB  - A strategy of cold loading of the Ca2+-indicating fluorophore Rhod 2-AM followed
      by warm incubation was developed to selectively label mitochondria of adult
      rabbit cardiac myocytes. After electrical stimulation, mitochondrial Rhod 2
      fluorescence observed by confocal microscopy increased and then rapidly decayed
      to baseline. In regions between mitochondria, the fluorescent transients were
      small or absent. Subsequent addition of calcium ionophore increased mitochondrial
      but not cytosolic fluorescence, confirming the mitochondrial localization of Rhod
      2. These experiments directly demonstrate rapid mitochondrial free Ca2+
      transients during the contractile cycle in rabbit cardiac myocytes.

PMID- 9245726
TI  - Isolation of three novel neuropeptides, the Cyanea-RFamides I-III, from
      Scyphomedusae.
AB  - Cnidarians are the lowest animal group having a nervous system. Using a
      radioimmunoassay for the C-terminal sequence Arg-Phe-NH2 (RFamide), we have
      isolated three novel neuropeptides from the jellyfish Cyanea lamarckii (belonging
      to the class Scyphozoa): (Glu-Trp-Leu-Arg-Gly-Arg-Phe-NH2 (Cyanea-RFamide I),
      (Glu-Pro-Leu-Trp-Ser-Gly-Arg-Phe-NH2 (Cyanea-RFamide II) and Gly-Arg-Phe-NH2
      (Cyanea-RFamide III). The Cyanea-RFamides are neuropeptides and form a peptide
      family with other known neuropeptides isolated from Hydra and hydromedusae
      (belonging to the class Hydrozoa), and various sea anemones and sea pansies
      (belonging to the class Anthozoa). The presence of RFamide neuropeptides in all
      major cnidarian classes suggests that this type of substance was among the first
      neurotransmitters used in evolution.

PMID- 9245727
TI  - Avian adenovirus induces ion channels in model bilayer lipid membranes.
AB  - The action of duck egg drop syndrome 1976 (EDS-76) adenovirus on model bilayer
      lipid membranes (BLM) has been investigated on planar egg phosphatidylcholine
      membranes and small unilamellar vesicles. It was found that the adenovirus formed
      channels in planar BLM in a pH-dependent manner. The addition of EDS-76 to planar
      BLM at pH 5 induced voltage-independent channel activity of about 60 pS
      conductivity after a lag phase. At pH 3, EDS-76 induced irregular spikes of
      current across the planar BLM which disappeared after several minutes. The
      adenovirus also was able to induce pH-dependent leakage of calcein-loaded
      liposomes. EDS-76 did not induce channel activity in planar BLM or liposome
      leakage at neutral pH.

PMID- 9245728
TI  - The membrane anchor of microsomal epoxide hydrolase from human, rat, and rabbit
      displays an unexpected membrane topology.
AB  - The microsomal epoxide hydrolase (mEH) and cytochrome P450s catalyze the
      sequential formation of carcinogenic metabolites. According to one algorithm for
      predicting the membrane topology of proteins, the human, the rabbit, and the rat
      mEH should adopt a type II topology. The type II topology is also predicted by a
      recently established neuronal network which is trained to recognize signal
      peptides with very high accuracy. In contrast to these predictions we find, based
      on N-glycosylation analysis in a cell-free and in a cellular system, that the
      membrane anchor of human, rat, and rabbit mEH displays a type I topology. This
      result is correctly predicted by the positive inside rule in which negatively
      charged residues, the distribution of which differs in the mEH membrane anchor of
      these species, have only a modulating role for the membrane topology of proteins.
      However, our results demonstrate that this role is not strong enough to force the
      mEHs into a type II topology, not even in the case of the rabbit mEH, in which
      the only positively charged residue in the C-terminal part of the topogenic
      sequence is flanked by five negatively charged residues.

PMID- 9245729
TI  - Effects of two hypertrophic cardiomyopathy mutations in alpha-tropomyosin,
      Asp175Asn and Glu180Gly, on Ca2+ regulation of thin filament motility.
AB  - The functional properties of wild type alpha-tropomyosin expressed in E. coli
      with an alanine-serine N-terminal leader (AS-alpha-Tm) were compared with those
      of AS-alpha-Tm with either of two missense mutations (Asp175Asn and Glu180Gly)
      shown to cause familial hypertrophic cardiomyopathy (FHC). Wild type AS-alpha-Tm
      and AS-alpha-Tm(Asp175Asn) binding to actin was indistinguishable from rabbit
      skeletal muscle ab-tropomyosin whilst the affinity of AS-alpha-Tm(Glu180Gly) was
      about threefold weaker. In vitro motility assays were performed with AS-alpha
      tropomyosin incorporated into skeletal muscle actin-rhodamine phalloidin
      filaments moving over skeletal muscle heavy meromyosin. Under relaxing conditions
      (pCa9), troponin added to actin filaments containing AS-alpha-tropomyosin or
      mutant tropomyosins resulted in normal switch-off, with a decrease in the
      fraction filaments moving from >80% to <20%. Under activating conditions (pCa5),
      troponin had a minor effect upon actin-AS-alpha-tropomyosin filament velocity
      (increased by 5 +/- 1%, n=10), whereas the velocity increased by 18 +/- 3% (n=7)
      with actin filaments containing AS-alpha-tropomyosin(Asp175Asn) and by 21 +/- 2%
      (n=8) with filaments containing AS-alpha-tropomyosin(Glu180Gly) (p<0.05 compared
      with AS-alpha-tropomyosin). Thus FHC mutations in alpha-tropomyosin produce
      detectable changes in the Ca2+-regulation of thin filaments, presumably via
      altered interaction with troponin.

PMID- 9245730
TI  - Multiple regulatory elements and binding proteins of the 5'-flanking region of
      the human estrogen-responsive finger protein (efp) gene.
AB  - The efp, a member of the RING finger family, was previously identified as an
      estrogen responsive gene. Here, we characterized basal promoter of the human efp
      gene. Transcription initiation site was found at position -60 G relative to the
      site for translation initiation, and TATA motif was absent. Deletion and mutation
      analyses of the 5'-flanking region using MCF-7 breast cancer cells indicated that
      the sequences located at -137 to -72 had the promoter activity for which an E-box
      (CACGTG) element at -110 to -105 was essential. EMSA showed that USF-1 bound to
      the E-box and that a protein-DNA complex was formed at the positive regulatory
      region (-137 to -110). Moreover, a strong negative regulatory region was present
      in -235 to -174. These findings suggest that the human efp promoter is regulated
      by multiple elements and their interacting factors, and the E-box near the
      transcription initiation site is essential for the basal promoter activity.

PMID- 9245731
TI  - Loss of activity of plasma platelet-activating factor acetylhydrolase due to a
      novel Gln281-->Arg mutation.
AB  - The prevalence of plasma platelet-activating factor (PAF) acetylhydrolase
      deficiency was investigated in 477 healthy Japanese individuals and 985 patients
      with various cardiovascular diseases. The genotype for this enzyme with regard to
      a G994-->T mutation (MM, normal; Mm, heterozygote; mm, mutant homozygote) was
      determined by an allele-specific polymerase chain reaction in 80 subjects shown
      to have no or low plasma activity (<10 nmol/min/ml). In 72 subjects, the genotype
      was consistent with plasma enzyme activity; 44 individuals with no activity were
      mm, and 28 with low activity were Mm. However, eight subjects with the MM
      genotype showed plasma enzyme activities of <10 nmol/min/ml. Determination of the
      DNA sequence of exon 9 of the plasma PAF acetylhydrolase gene in these eight
      subjects revealed a previously unidentified A1001-->G missense mutation,
      resulting in a Gln281-->Arg substitution, in a 72-year-old woman with coronary
      artery disease, essential hypertension, and no plasma enzyme activity. Site
      directed mutagenesis in vitro showed that the corresponding recombinant mutant
      protein lacked PAF acetylhydrolase activity. Thus, the Gln281-->Arg substitution
      appears responsible for the loss of plasma PAF acetylhydrolase activity.

PMID- 9245732
TI  - Molecular characterization of the promoter region of a neuroendocrine tumor
      marker, IA-1.
AB  - IA-1 is an intronless gene, which encodes a 510 amino acid protein with a zinc
      finger DNA-binding motif that is expressed in tumors of neuroendocrine origin.
      The 5'-upstream region of the IA-1 gene was recently sequenced. In this paper,
      the regulatory elements and the promoter region of the 5'-upstream region were
      analyzed by use of a series of deletion mutants (ranging from +26 bp to -2090 bp
      upstream of the IA-1 gene), which were tested in a pituitary tumor cell line, AtT
      20, and Hela cells by transient transfection assays. These experiments showed
      that a 506 base pair upstream sequence was sufficient for maximal expression of a
      reporter gene. Multiple known regulatory elements were found within this region
      including three E boxes and a clustered Sp-1 site. In addition, Southwestern blot
      analysis, using a radiolabeled promoter sequence (extending from -108 bp to -66
      bp) and nuclear extracts from both neuroendocrine and non-neuroendocrine cell
      lines, revealed four promoter binding proteins designated PBP1, PBP2, PBP3 and
      PBP4 with molecular weights of 55 kD, 32 kD, 29 kD, and 27/28 kD, respectively.
      These studies suggest that several different regulatory elements in the 5'
      upstream region of the IA-1 gene and at least four different nuclear proteins may
      be involved in the cell-specific expression of IA-1.

PMID- 9245733
TI  - Novel SnoRNAs from Naja naja atra (Taiwan cobra) and Bungarus multicinctus
      (Taiwan banded krait), form extended sequence complementarity to 5S rRNA.
AB  - During the mapping and sequencing of Naja naja atra cobrotoxin and cardiotoxin 4
      genes, we have found that novel small nucleolar RNAs (snoRNAs) are encoded in the
      first intron of the two genes. The snoRNAs in Naja naja atra were amplified from
      the venom glands cDNA mixtures of Naja naja atra by reverse transcription
      polymerase chain reaction using the primers designed from the first intronic
      sequences of cobrotoxin and cardiotoxin 4 genes. Likewise, the snoRNAs in
      Bungarus multicinctus were also amplified by the same primers. Comparison of
      these snoRNA genes reveals that the regions involved in binding to 5S rRNA are
      highly conserved among these genes, and form 12-nt and 15-nt tracts of
      complementarity to phylogenetically invariant sequences in eukaryotic 5S rRNAs.
      The box C sequence in these snoRNAs is consensus, however, variations with the
      sequence of box D motif are observed. The present study is the first case of
      intron-encoded snoRNAs contain extended regions of perfect complementarity to
      mature 5S rRNA.

PMID- 9245734
TI  - Isolation of a genetic locus associated with metronidazole resistance in
      Helicobacter pylori.
AB  - We examined the molecular mechanism of metronidazole resistance by constructing a
      lambda-Zap II phagemid expression library with genomic DNA from a metronidazole
      resistance strain of Helicobacter pylori. Twenty-two clones were found to have
      elevated MTZ resistances in XLOLR strain of E. coli. Phagemids belonging to the
      twenty two clones were extracted and then retransformed into the XLOLR strain of
      E. coli. After MTZ selection, five clones could confer metronidazole resistance
      consistently. According to Southern hybridization and DNA sequencing, the five
      clones contained a same locus, recA. In addition, transforming the five clones
      into BL21 strain of E. coli produced a higher resistance to MTZ. Interestingly,
      electroporation of one of the five phagemid clones into two MTZ sensitive H.
      pylori yielded MTZ resistant strains. Comparing amino acid sequence in MTZ
      resistant with sensitive isolates revealed two point mutations at this locus.
      Above results suggest that mutation in recA may be associated with metronidazole
      resistance of H. pylori.

PMID- 9245735
TI  - Cloning of rat Muc5AC mucin gene: comparison of its structure and tissue
      distribution to that of human and mouse homologues.
AB  - The human mucin gene MUC5AC codes for a large mucin which has tandem repeat units
      and cysteine rich regions characteristic of several members of this class of
      glycoproteins. Human epithelia expressing the mucin include that of stomach,
      bronchus/trachea, endocervix and conjunctiva. We report here a 3.8 kb partial
      sequence of a rat homologue for the human MUC5AC gene and compare its tandem
      repeat sequence and cysteine rich domains to those of the human and mouse gene.
      Rat and mouse have the same number of amino acids (16) in their Muc5AC tandem
      repeat units and share 69% sequence similarity, whereas human MUC5AC has only 8
      amino acids in its tandem repeat. In rat, the tandem repeat domain is flanked at
      its 3' end by a non-repeat region coding for 1142 amino acids. Four cysteine rich
      subdomains were identified in this region; one of these has 64% similarity to a
      corresponding region in human MUC5AC and 80% similarity to a mouse MUC5AC
      cysteine rich region. Southern blot analysis revealed cross hybridization of a
      probe for the rat cysteine rich region, to human, mouse, rabbit, and porcine
      genomic DNA; the rat tandem repeat probe hybridized with mouse and rabbit only.
      Unlike humans, rat expressed MUC5AC message detectable by Northern blot and in
      situ hybridization only in stomach epithelium and conjunctival goblet cells.

PMID- 9245736
TI  - Effects of nucleotides on the denaturation of F actin: a differential scanning
      calorimetry and FTIR spectroscopy study.
AB  - We have utilized DSC and high pressure FTIR spectroscopy to study the specificity
      and mechanism by which ATP protects actin against heat and pressure denaturation.
      Analysis of the thermograms shows that ATP raises the transition temperature Tm
      for actin from 69.6 to 75.8 degrees C, and the calorimetric enthalpy, deltaH,
      from 680 to 990 kJ/mole. Moreover, the peak becomes sharper indicating a more
      cooperative process. Among the other nucleotide triphosphates, only UTP increases
      the Tm by 2.5 degrees C, whereas GTP and CTP have negligable effects; ADP and AMP
      are less active, increasing the Tm by 2.1 and 1.6 degrees C, respectively.
      Therefore, gamma phosphate plays a key role in this protection, but its
      hydrolysis is not implicated since the nonhydrolysable analogue of ATP, ATP-PNP
      have the same activity as ATP. FTIR spectroscopy demonstrates that ATP also
      protects actin against high pressure denaturation. Analysis of the amide I band
      during the increase in pressure clearly illustrates that ATP protects
      particularly a region rich in beta-sheets of the actin molecule.

PMID- 9245737
TI  - Increased transcript level of RBM3, a member of the glycine-rich RNA-binding
      protein family, in human cells in response to cold stress.
AB  - Although the cold-shock responses of microorganisms have been extensively
      investigated, those of mammalian cells are just beginning to be understood.
      Recently, CIRP, a member of the glycine-rich RNA-binding protein (GRP) family,
      has been identified as the first cold-shock protein in mammalian cells. Here, we
      report that RBM3, another member of the GRP family, is induced in human cells in
      response to cold stress (32 degrees C). RBM3 transcripts were constitutively
      expressed in all cell lines examined including K562, HepG2, NC65, HeLa, and T24
      cells. In all of them, the transcript levels of RBM3 were increased at 24 h after
      the 37 to 32 degrees C temperature down-shift. In NC65 cells, the kinetics of
      RBM3 induction was different from that of CIRP. Protein synthesis inhibitors
      cycloheximide and puromycin induced RBM3 transcripts, but cadmium chloride, H2O2,
      ethanol, and osmotic shock had no effect. Combined with the different tissue
      distribution of expression, these results suggest that RBM3 and CIRP play
      distinct roles in cold responses of human cells.

PMID- 9245738
TI  - Evidence that the transit of glucose into liver microsomes is not required for
      functional glucose-6-phosphatase.
AB  - We show that the production of glucose from glucose-6-phosphate hydrolysis
      outside microsomes is a function of glucose-6-phosphatase independent of its
      property to form glucose inside microsomes. Indeed, during development (before 1
      day of age), mouse liver microsomes had glucose-6-phosphatase producing glucose
      solely outside microsomes. Furthermore, in vivo treatment of rats with the
      glucocorticoid analogue triamcinolone resulted in increased glucose-6-phosphatase
      activity outside but not inside microsomes and without change in the catalytic
      subunit 40 kDa glucose-6-phosphatase mRNA abundance or protein level, indicating
      that other factors induced by triamcinolone (e.g., altered membrane lipid
      environment and/or a regulatory protein) were responsible for the activity
      change. Triamcinolone treatment also lessened the inhibition of glucose-6
      phosphatase by pyridoxal 5'-phosphate (PLP), but this effect was not due to an
      interaction of PLP with the active site. Accordingly, reversal of the inhibition
      was observed after permeabilization of the microsomes. The two distinct
      orientations of liver microsomal glucose-6-phosphate phosphohydrolase suggest
      different physiological roles played by this enzyme in the endoplasmic reticulum
      membrane.

PMID- 9245739
TI  - Leukaemia inhibitory factor induces mitogenesis in Swiss 3T3 cells and selective
      enhancement via a variety of signalling events.
AB  - Leukaemia inhibitory factor (LIF) stimulates cellular DNA synthesis in confluent
      quiescent Swiss 3T3 cells. Insulin and prostaglandin E1 (PGE1), which fail to
      stimulate DNA synthesis alone, potentiate this effect. Prostaglandin F2alpha
      (PGF2alpha), which is mitogenic in these cells, enhances the effect of LIF on DNA
      synthesis. TGFbeta1 increases the effect of PGF2alpha but not that of LIF. R
      59022, a diacylglycerol kinase inhibitor which increases protein kinase C (PKC)
      activity, enhances only the PGF2alpha response. 13-Tetradecanoyl-12
      phorbolacetate-mediated PKC depletion prevents the action of PGF2alpha but not
      that of LIF, nor the PGF2alpha potentiation of LIF-stimulated DNA synthesis. 1
      Oleoyl-2acetylglycerol, a PKC and tyrosine kinase (TK) activator which mimics
      some of the PGF2alpha effects, enhances only LIF-induced DNA synthesis in cells
      possessing intact PKC activity. These results suggest that stimulation of DNA
      synthesis by LIF, as well as its enhancement by PGF2alpha, may occur via a
      signalling pathway independent of PKC activation.

PMID- 9245740
TI  - Interference with c-myc expression and RB phosphorylation during TNF-mediated
      growth arrest in human endothelial cells.
AB  - Incorporation of [3H]-thymidine into DNA in non-synchronized cultures of human
      endothelial cells was blocked by a 24 h exposure to TNF in a dose dependent
      manner that resulted in accumulation of cells in G1, as assayed by flow cytometry
      analysis of DNA content. Proliferation restarted when cells were replated in the
      absence of TNF. Northern analysis of c-myc mRNA in synchronized untreated
      cultures showed a transient increase previous to DNA synthesis that was decreased
      with TNF treatment. Western analysis of the retinoblastoma gene product RB in
      untreated synchronized cultures showed reduced electrophoretic mobility during
      the transition from G1 to S, congruent with RB inactivation by phosphorylation.
      TNF treatment prevented RB retardation and reduced total levels of RB protein.
      Taken together our results show that the TNF-mediated block of endothelial
      proliferation correlates with deficient activation of the G1 events necessary for
      entry into S, despite the presence of serum and endothelial mitogens.

PMID- 9245742
TI  - The TNF-beta gene Nco I polymorphism is not associated with hypertriglyceridemia
      or insulin resistance in lean and obese subjects.
AB  - Interindividual differences in TNF-alpha monocyte responses can be accounted for
      by genetic polymorphisms at the TNF-beta locus defined by the Nco I restriction
      enzyme. Higher triglyceride levels in non-insulin-dependent diabetic patients
      homozygous at the 10.5-kb fragment of the TNF-beta gene have been described. The
      aim of this study was to investigate whether the Ncol polymorphism of the TNF
      beta gene influences the relationship between insulin resistance and triglyceride
      levels. Thirty-eight healthy volunteers were divided into two groups according to
      the absence [homozygous for class 1 allele (1/1), n=16] or presence of the class
      2 allele [n=22; 19 heterozygous (1/2), and 3 homozygous (2/2)]. Both groups were
      comparable in sex, age, BMI, waist/hip ratio, fat mass and percentage of body fat
      as measured by bioelectric impedance, skinfold measurements, and blood pressure
      (all p>0.05). There were no differences in serum cholesterol (total, or HDL and
      VLDL fractions) or in total or VLDL triglycerides between the groups (all
      p>0.05). The insulin sensitivity index (Minimal Model method) was comparable for
      the two groups. In summary, the 10.5-kb homozygous genotype of the TNF-beta locus
      does not contribute to differences in triglyceride levels or insulin sensitivity
      among nondiabetic subjects.

PMID- 9245741
TI  - Preferential overexpression of a class MU glutathione S-transferase subunit in
      mouse liver by myristicin.
AB  - The present studies were undertaken to elucidate the mechanism of induction of
      glutathione S-transferase (GST) in mouse liver by myristicin, an active
      constituent of parsley leaf. A/J albino mice, given 5 to 50 mg doses of
      myristicin, showed 4- to 14-fold increase in liver GST specific activity over the
      control. GST purified from equal amounts of control and myristicin-treated livers
      indicated a marked increase in the GST activity. A relatively higher increase in
      GST activity towards 2,4-dichloronitrobenzene and a profound increase in the
      levels of GST mu on Western blot analysis of the myristicin-treated mouse liver
      suggest a preferential induction of GST mu. Results of the study also indicate
      that out of the two mu class GST subunits (Mr. 26,500 and Mr. 25,000) expressed
      in liver only one (Mr. 26,500) is significantly elevated. Myristicin treatment
      caused a slight change in the GST pi levels while the levels of GST alpha showed
      a modest increase. These results suggest that myristicin could be an effective
      chemopreventive agent, particularly for carcinogens that are detoxified by the mu
      class GST.

PMID- 9245743
TI  - EDITORIAL

PMID- 9245744
TI  - In Memoriam: Albert Christian Kolbye, Jr. (1935-1996)

PMID- 9245745
TI  - CAST Task Force Reports and ISRTP

PMID- 9245746
TI  - EDITORIAL

PMID- 9245747
TI  - Investigating the cytoskeleton of chicken cardiocytes with the atomic force
      microscope.
AB  - We have investigated living chicken cardiocytes with an atomic force microscope
      (AFM). Cytoskeletal structures like stress fibers can easily be imaged with the
      AFM. Here we have also measured the cell's elastic properties. By taking force
      curves as a function of lateral position (force mapping) we could compare the
      elastic properties at different locations of the same cell. In the lamellipodal
      region investigated here in detail, the elastic moduli range from around 10 up to
      200 kPa on top of stress fibers. By degradation with cytochalasin B we can
      estimate to what extent the elastic properties of this type of cell are
      determined by the actin network.

PMID- 9245748
TI  - Imaging Plasmodium falciparum-infected ghost and parasite by atomic force
      microscopy.
AB  - Atomic force microscopy was used to image the membrane cytoskeleton network of
      normal and P. falciparum-infected ghosts. The membrane cytoskeleton network was
      examined in air-dried ghost preparations from normal and infected cells. We found
      that the spectrin network was changed in infected ghosts. The thickness of the
      normal red cell membrane was about 15.05 +/- 2.27 nm, while the thickness of the
      P. falciparum-infected membrane was found to be 22.97 +/- 3.84 nm. The ghost
      containing ring stage parasites exhibited areas of particle-like protrusions
      ranging in size from 0.2 to 0.7 micron. The surface of the P. falciparum parasite
      was also imaged in air-dried samples, showing the existence of a large protrusion
      extending from the parasite surface.

PMID- 9245749
TI  - Properties of biomolecules measured from atomic force microscope images: a
      review.
AB  - AFM images can be used to obtain quantitative or qualitative information about
      the properties of biomaterials. Examples presented here are: (1) Persistence
      length measurements of moving and stationary DNA molecules. (2) Force mapping to
      measure properties such as the elasticity of cells and vesicles. (3) Phase mode
      imaging to detect variations in materials and properties of the sample surface.
      (4) Imaging of surfaces at different constant forces.

PMID- 9245750
TI  - Visualization of poly(A)-binding protein complex formation with poly(A) RNA using
      atomic force microscopy.
AB  - Poly(A)-binding protein (PABP) is an RNA-binding protein that binds specifically
      to the poly(A) tail of messenger RNAs in eukaryotes. The PABP/poly(A) tail
      complex has been implicated as being important in promoting the efficient
      initiation of translation as well as in maintaining the integrity of the mRNA.
      PABP binds poly(A) cooperatively with a packing density of one PABP molecule per
      25 adenosine residues. We have investigated the complexes formed between purified
      PABP and poly(A) RNA using atomic force microscopy (AFM). PABP alone was observed
      to be primarily in a monomer form with a height of 1.0 +/- 0.2 nm. Following
      binding to poly(A), PABP appeared to be present in variable size complexes that
      bound lengthwise along the RNA. This size of the PABP/poly(A) complex appeared to
      be maximal, suggesting that PABP binding to poly(A) may be self-limiting. Poly(A)
      RNA alone appeared to contain a knob-like structure that largely disappeared once
      PABP was bound. The use of AFM has therefore provided potential new insights into
      the complexes formed by this RNA-binding protein.

PMID- 9245752
TI  - S-layer stabilized solid support lipid bilayers.
AB  - This work describes composite structures composed of lipid bilayer or
      tetraetherlipid monolayer films attached to solid supports with associated
      crystalline bacterial cell surface layers (S-layers). The bilayer system was
      established by making use of the strong chemisorption of a first monolayer of
      thiolipids (1-octadecanethiol or 1,2-dimyristoyl-sn-glycero-3-phosphothioethanol)
      on gold and attaching a second monolayer of 1,2-dipalmitoyl-sn-3
      phosphatidylethanolamine by the Langmuir Schaefer technique. The tetraetherlipid
      monolayer was composed of Glycerol-dialkyl-nonitol tetraetherlipid (GDNT). The
      monolayer of GDNT exhibits the thickness of a bilayer with hydrophilic headgroups
      on both sides and a hydrophobic inner part. Isolated S-layer protein from
      Bacillus sphaericus (CCM2177, which was injected into the subphase of an LB
      trough, recrystallized into a coherent monolayer at the solid supported
      phospholipid bilayer and at the tetraehtherlipid monolayer. The composite lipid/S
      layer structures were stable enough to allow lifting from the air-water
      interface, rinsing in water, and transfer into a scanning force microscope.

PMID- 9245751
TI  - Direct visualization of collagen-bound proteoglycans by tapping-mode atomic force
      microscopy.
AB  - Most studies on the interaction of collagen with proteoglycans, two universal
      components of connective tissues, use technical approaches which substantially
      modify the shape and size of the proteoglycans themselves. In the present study
      unfixed, untreated collagen fibrils from rat tail tendon were dehydrated and
      observed by tapping-mode atomic force microscopy. The surface of collagen fibrils
      immediately reveals a periodic alternation of gap and overlap zones. A thin,
      transverse ridge decorates the gap zone, while other filamentous structures run
      on the fibril surface, either parallel or perpendicular to the fibril axis. These
      surface structures are much enhanced by Cupromeronic Blue preincubation, while
      pretreatment with chondroitinase ABC removes them completely, leaving barely
      detectable transverse ridges. The ridge and filaments are likely to represent,
      respectively, the core protein and the glycosaminoglycan side chains of
      proteoglycans, displayed with a far better resolution than with conventional
      histochemical or immunohistochemical techniques. Our data suggest that
      proteoglycan molecules are capable of different, multiple interactions with the
      collagen fibril surface as well as with each other.

PMID- 9245753
TI  - High-Resolution Atomic Force Microscopy of Native Valonia Cellulose I
      Microcrystals
AB  - We have studied the surface of native Valonia cellulose I microcrystals under
      propanol and waterby atomic force microscopy (AFM). Ultra-high-resolution images
      of the surface are presented, as well as lower resolution morphological
      observations of whole crystals. The pitch of 0.52 nm along the molecule due to
      the asymmetrical glucose unit and the intermolecular spacing of approximately 0.6
      nm are clearly resolved in both imaging environments. The relationship between
      the crystalline bulk and the surface are discussed, with particular attention
      being paid to previous crystallographic studies. We also show that the glucose
      units along the cellulose chains are not topographically equivalent due to the
      twofold screw symmetry and accordingly present strong evidence of triclinic
      character by direct surface imaging, rather than by taking average measurements
      in reciprocal space. The crystallographic distinction between monoclinic and
      triclinic structure is a displacement of the cellulose chains by a quarter of the
      c axis period, resulting in either a stagger or a diagonal shifting,
      respectively, of the cellobiose unit along the chain axis by 0.26 nm. This
      structural identification (in real space) represents, as far as we are aware, the
      highest resolution AFM imaging of a biological specimen to date. This study opens
      up the future possibility of identifying the localized triclinic or monoclinic
      nature of the Valonia cellulose surface with AFM.

PMID- 9245754
TI  - Chloroplast F0F1 ATP Synthase Imaged by Atomic Force Microscopy
AB  - The F0F1 ATP synthase of chloroplasts was imaged using atomic force microscopy
      (AFM) in contact mode under physiological conditions. Chloroplast (CF0F1) ATP
      synthases were reconstituted into liposomes. Liposomes were adsorbed on a mica
      surface where they spread and formed lipid bilayers containing CF0F1 ATP
      synthases which could be imaged. From these reconstituted CF0F1 ATP synthases,
      the CF1 part could be removed either by application of a chemical denaturant or
      less efficiently by mechanical stripping with the AFM tip. Embedded in the lipid
      bilayer were seen ring-like structures with a central dimple with outer diameters
      of 20 +/- 3 nm (chemical denaturant) and ca. 7 nm (mechanical stripping),
      respectively. Ring-like structures were also observed in a protein-free lipid
      bilayer. These had diameters of 30 +/- 5 nm and could be clearly distinguished
      from the structures observed after mechanical stripping. Hence, the ring-like
      structures observed after mechanical stripping might represent the intrinsic
      membrane domain CF0 or the oligomer of its subunit III. In addition, isolated CF1
      adsorbed directly onto the mica surface was imaged. In accordance with the size
      known from electron microscopy, a diameter of 13 +/- 4 nm was measured.

PMID- 9245755
TI  - Structural changes in native membrane proteins monitored at subnanometer
      resolution with the atomic force microscope: a review.
AB  - Three membrane proteins, OmpF porin from Escherichia coli, bacteriorhodopsin from
      Halobacterium salinarium, and the hexagonally packed intermediate (HPI) layer
      from Deinoccocus radiodurans, were investigated with the atomic force microscope
      in buffer solution. A resolution of up to 0.8 nm allowed structural differences
      of individual proteins to be detected. OmpF porin exhibits different static
      conformations on the outer surface, which possibly represent the two conductive
      states of the ion channels. Reversible structural changes in the cytoplasmic
      surface of purple membrane have been induced by changing the force applied to the
      scanning stylus: doughnut-shaped bacteriorhodopsin trimers transformed into a
      structure with three pronounced protrusions when the force was reduced from 300
      to 100 pN. Furthermore, individual pores of the inner surface of the HPI layer
      were observed to switch from an "open" to a "closed" state. Together, the
      structural changes in proteins monitored under physiological conditions suggest
      that direct observation of function-related conformational changes of
      biomolecules with the atomic force microscope is feasible.

PMID- 9245756
TI  - Atomic Force Sensing of Light-Induced Protein Dynamics with Microsecond Time
      Resolution in Bacteriorhodopsin and Photosynthetic Reaction Centers
AB  - This paper reports on experiments that have monitored protein microsecond
      dynamics with a cantilevered near-field optical glass fiber. In these experiments
      two photoactive proteins, bacteriorhodopsin (bR) and the photosynthetic reaction
      center (PS I), are used to demonstrate that such probes can measure light-induced
      microsecond protein dynamics even though the resonance frequencies of the glass
      cantilevers used are on the order of a few hundred kilohertz. In the case of the
      light-driven proton pump, bR, the light-induced atomic force sensing (AFS) signal
      is negative (indicating contraction) in the microsecond time domain of the L
      photointermediate and becomes positive (corresponding to expansion) in the
      subsequent M intermediate that lives for milliseconds. Double pulse experiments
      from M to bR show that the latter process reverses the AFS signal. Thus, the AFS
      structural changes are coupled with the (optical) photocycle intermediates. Light
      induced contraction and expansion phenomena are also observed in the case of PS
      I. In both systems the time regime of the dynamic phenomena that have been
      measured with AFS is five orders of magnitude faster than the fastest previously
      recorded atomic force detection of dynamic phenomena. This advance portends a new
      era in dynamic imaging of protein conformational changes.

PMID- 9245757
TI  - Probing single biomolecules with atomic force microscopy.
AB  - During the last years, atomic force microscopy (AFM) has developed from a
      microscopy tool for solid-state surface science toward a method employed in many
      scientific disciplines, such as biology, for investigating individual molecules
      on a nanometer scale. This article describes the current status of the imaging
      possibilities of AFM on RNA, IgG, and gold-labeled cell adhesion proteoglycans,
      as well as of measurements of intermolecular binding forces between biomolecules
      in order to investigate their molecular structure, function, and elasticity.

PMID- 9245758
TI  - Adsorption of biological molecules to a solid support for scanning probe
      microscopy.
AB  - Scanning probe microscopes are now established tools to study the surface
      structure of biological macromolecules under physiological conditions. Sample
      preparation methods for this microscopy all have the objective to attach the
      specimen firmly to a support. Here we analyse the commonly used method of
      adsorbing biological specimens to freshly cleaved mica. This is facilitated by
      adjusting the electrolyte concentration and the pH of the buffer solution. Native
      macromolecular systems absorbed to mica in this way can be reproducibly imaged at
      submolecular resolution.

PMID- 9245759
TI  - Bioreactive self-assembled monolayers on hydrogen-passivated Si(111) as a new
      class of atomically flat substrates for biological scanning probe microscopy.
AB  - This is the first report of bioreactive self-assembled monolayers, covalently
      bound to atomically flat silicon surfaces and capable of binding biomolecules for
      investigation by scanning probe microscopy and other surface-related assays and
      sensing devices. These monolayers are stable under a wide range of conditions and
      allow tailor-made functionalization for many purposes. We describe the substrate
      preparation and present an STM and SFM characterization, partly performed with
      multiwalled carbon nanotubes as tapping-mode supertips. Furthermore, we present
      two strategies of introducing in situ reactive headgroup functionalities. One
      method entails a free radical chlorosulfonation process with subsequent
      sulfonamide formation. A second method employs singlet carbenemediated hydrogen
      carbon insertion of a heterobifunctional, amino-reactive trifluoromethyl
      diazirinyl crosslinker. We believe that this new substrate is advantageous to
      others, because it (i) is atomically flat over large areas and can be prepared in
      a few hours with standard equipment, (ii) is stable under most conditions, (iii)
      can be modified to adjust a certain degree of reactivity and hydrophobicity,
      which allows physical adsorption or covalent crosslinking of the biological
      specimen, (iv) builds the bridge between semiconductor microfabrication and
      organic/biological molecular systems, and (v) is accessible to nanopatterning and
      applications requiring conductive substrates.

PMID- 9245760
TI  - Photonic force microscope based on optical tweezers and two-photon excitation for
      biological applications.
AB  - A new scanning probe microscope, the photonic force microscope (PFM), based on
      optical tweezers and two-photon absorption processes for biological applications
      is described. Optical tweezers are used to trap a fluorescent latex bead with a
      diameter of 200 nm in an aqueous solution in all three dimensions. The
      fluorescent dye is chosen to fulfill the two-photon absorption criterion for the
      1064-nm line of a Nd:YVO4 laser. The intensity of the fluorescence emission is
      utilized as a very sensitive position sensor along the optical axis. Two
      dimensional images are formed by laterally scanning the trapped latex bead across
      biological samples while recording the two-photon-induced fluorescences
      intensity. A scanning probe image of the outer surface of a small neurite from a
      cultured rat hippocampal neuron is shown, which is hardly visible under
      differential interference contrast microscopy. The lateral resolution is given by
      the bead diameter; the axial resolution is 40 nm. Under the experimental
      conditions the maximal imaging force applied by the probe is below 5 pN.

PMID- 9245761
TI  - Hydration scanning tunneling microscopy of DNA and a bacterial surface protein.
AB  - Hydration scanning tunneling microscopy is based on the electrical conductivity
      of molecularly thin water layers which adsorb to the sample surfaces in a humid
      atmosphere. It allows reliable imaging of biological specimens and even
      insulators, provided they are hydrophilic. Here, we present results obtained with
      linearized plasmid DNA on mica and a bacterial surface protein layer (the HPI
      layer). A width of 3 nm was measured for the DNA molecules and a quasi-periodic
      structure along the molecules with a repeat distance of about 5 nm was observed.
      We show that-depending on the tunneling voltage-there are two different imaging
      modes for the DNA samples: at higher voltages, real tunneling or field emission
      is responsible for the charge transfer between tip and sample. In contrast, at
      lower voltages we found indications of a water meniscus between tip and surface.
      The HPI layer, however, seems to be imaged at most voltages without a water
      meniscus.

PMID- 9245762
TI  - Near-field fluorescence imaging of genetic material: toward the molecular limit.
AB  - Chromosomes, DNA, and single fluorescent molecules are studied using an aperture
      type near-field scanning optical microscope with tuning fork shear force
      feedback. Fluorescence in situ hybridization labels on repetitive and single copy
      probes on human metaphase chromosomes are imaged with a width of 80 nm, allowing
      their localisation with nanometer accuracy, in direct correlation with the
      simultaneously obtained topography. Single fluorophores, both in polymer and
      covalently attached to amino-silanized glass, are imaged using two-channel
      fluorescence polarization detection. The molecules are selectively excited
      according to their dipole orientation. The orientation of the dipole moment of
      all molecules in one image could be directly determined. Rotational dynamics on a
      10-ms to 100-s timescale is observed. Finally, shear force imaging of double
      stranded DNA with a vertical sensitivity of 0.2 nm is presented. A DNA height of
      1.4 nm is measured, which indicates the nondisturbing character of the shear
      force mechanism.

PMID- 9245763
TI  - The atomic force microscope as a new microdissecting tool for the generation of
      genetic probes.
AB  - The atomic force microscope (AFM) can be used to visualize and to manipulate
      biological material with relative case and high resolution. This study was
      carried out to investigate whether probe sets, specific for subregions of the
      human genome and useful for the painting of chromosome bands, can be established
      by PCR amplification of AFM-dissected chromosome regions. Compared to standard
      microdissection techniques, the AFM can be used with much higher precision for
      the dissection of the region of interest and subsequent nanoextraction of DNA
      material. After scanning the area of interest in noncontact mode AFM, chromosome
      bands were cut by the AFM tip at high force. The genetic material of a single cut
      attached itself to the tip and was extracted and amplified using degenerate
      oligonucleotide-primed-PCR. Subsequent to hapten labeling, fluorescence in situ
      hybridization was performed and chromosome band-specific probes were visualized
      by standard fluorescence microscopy.

PMID- 9245764
TI  - Microstructural features of non-union of human humeral shaft fracture.
AB  - Microstructures of non-unions of human humeral shaft fractures were investigated
      by using scanning electron microscopy, transmission electron microscopy, and X
      ray microdiffraction. The non-union has a trabeculae structural framework similar
      to woven bone. Among the trabeculae are cavities that are subdivided into small
      chambers by thin plates of collagen fibrils. Some chambers are filled with
      variously shaped mineralized particles several micrometers in size. The collagen
      fibrils in both the trabeculae and the thin plates were only slightly mineralized
      by hydroxyapatite. Vesicles loaded with noncrystalline calcium phosphate (NCP)
      were observed in most mineralized particles, and brushite crystals with special
      morphology were seen to be embedded in some particles in irregular shapes. X-ray
      microdiffraction results indicated that the mineral phases in the non-unions were
      mainly NCP in addition to small amounts of hydroxyapatite and brushite. NCP
      deposition and insufficient mineralization of the collagen fibrils may be two
      important microstructural features of the non-unions of human humeral shaft
      fractures different from normally repaired bone callus.

PMID- 9245765
TI  - "Exolysosomes," enzyme-containing vesicles in the ecdysial space of molting
      crabs.
AB  - Free vesicle-like bodies (VLBs) present in the ecdysial space of cuticle regions
      undergoing degradation during preecdysis of the Atlantic shore crab Carcinus
      maenas have been interpreted either as infectious organisms or as secretion
      structures associated with degradation of the old cuticle. Ultrastructural,
      cytochemical, and immunocytological investigations were performed to test these
      hypotheses and to see whether VLBs are peculiar to this crab species. Similar
      VLBs were systematically found in two other preecdysial crabs, Cancer pagurus and
      Macropipus puber. In Car, maenas, they originate during early premolt inside
      Golgi buddings and are often gathered into large vacuoles in epidermal cells. The
      histochemical azo-dye technique and a cerium-based cytochemical method revealed
      acid phosphatase activity in both the ecdysial space and the VLBs, while
      Feulgen's method and immunocytological labeling always failed to reveal any DNA
      or RNA in either the ecdysial space or the VLBs. We conclude that VLBs are not
      infectious organisms but "extracellular" cuticle-degrading organelles of
      lysosomal origin and propose to coin them "exolysosomes."

PMID- 9245766
TI  - Electron tomography of neuronal mitochondria: three-dimensional structure and
      organization of cristae and membrane contacts.
AB  - The structure of neuronal mitochondria from chick and rat was examined using
      electron microscope tomography of chemically fixed tissue embedded in plastic and
      sliced in approximately 500 nm-thick sections. Three-dimensional reconstructions
      of representative mitochondria were made from single-axis tilt series acquired
      with an intermediate voltage electron microscope (400 kV). The tilt increment was
      either 1 degree or 2 degrees ranging from -60 degrees to +60 degrees. The
      mitochondrial ultrastructure was similar across species and neuronal regions. The
      outer and inner membranes were each approximately 7 nm thick. The inner boundary
      membrane was found to lie close to the outer membrane, with a total thickness
      across both membranes of approximately 22 nm. We discovered that the inner
      membrane invaginates to form cristae only through narrow, tubular openings, which
      we call crista junctions. Sometimes the cristae remain tubular throughout their
      length, but often multiple tubular cristae merge to form lamellar compartments.
      Punctate regions, approximately 14 nm in diameter, were observed in which the
      inner and outer membranes appeared in contact (total thickness of both membranes
      approximately 14 nm). These contact sites are known to a play a key role in the
      transport of proteins into the mitochondrion. It has been hypothesized that
      contact sites may be proximal to crista junctions to facilitate transport of
      proteins destined for the cristae. However, our statistical analyses indicated
      that contact sites are randomly located with respect to these junctions. In
      addition, a close association was observed between endoplasmic reticulum
      membranes and the outer mitochondrial membrane, consistent with the reported
      mechanism of transport of certain lipids into the mitochondrion.

PMID- 9245767
TI  - Structural Analysis of Photosystem II: Comparative Study of Cyanobacterial and
      Higher Plant Photosystem II Complexes
AB  - Oxygen evolving photosystem II (PSII-OEC) complexes and PSII core complexes were
      isolated from spinach and the thermophilic cyanobacterium Synechococcus sp. OD24
      and characterized by gel electrophoresis, immunoblotting, and absorbance
      spectroscopy. The mass of the core complexes was determined by scanning
      transmission electron microscopy (STEM) and found to be 281 &plusmn; 65 kDa for
      spinach and 313 &plusmn; 52 kDa for Synechococcus sp. OD24. The mass of the
      spinach PSII-OEC complex was 327 &plusmn; 64 kDa. Digital images of negatively
      stained PSII-OEC and PSII core complexes were recorded by STEM and analyzed by
      single particle averaging. All monomeric complexes showed similar morphologies
      and were of comparable length (14 nm) and width (10 nm). The averages revealed a
      pseudo-twofold symmetry axis, which is a prominent structural element of the
      monomeric form. Difference maps between the averaged projections of the oxygen
      evolving complexes and the core complexes from both species indicated where the
      33-kDa extrinsic manganese stabilizing protein is bound. A symmetric organization
      of the PSII complex, with the PsbA and the PsbD proteins in the center and
      symmetrically arranged PsbB and PsbC proteins at the periphery of the monomeric
      complex, is proposed.

PMID- 9245768
TI  - Nuclear Pore Complex Structure in Birds
AB  - The nuclear envelope consists of two parallel membranes enclosing an aqueous
      lumen. In places there are pores in both membranes at which the two membranes are
      joined. Within these pores reside the nuclear pore complexes. The current
      structural models of the nuclear pore complex have been derived from a number of
      studies using different electron microscopical techniques. Recently, using
      surface imaging techniques such as field emission in-lens scanning electron
      microscopy, novel structures have been identified, particularly at the periphery
      of the structure, most notably the nucleoplasmic basket. One limitation of the
      current models is that they are based almost entirely on nuclear envelopes
      isolated from amphibian oocytes and a pressing question is whether this structure
      is the same in other organisms and tissues. Here we have studied the structure of
      nuclear envelopes isolated from bird oocytes. We show that the overall structure
      is remarkably conserved. In particular, recently discovered peripheral structures
      appear very similar. We see variations in basket conformation but believe that
      this is related to the functional states of individual pore complexes.

PMID- 9245769
TI  - Actin: from cell biology to atomic detail.
AB  - Over the past 2 decades our knowledge about actin filaments has evolved from a
      rigid "pearls on a string" model to that of a complex, highly dynamic protein
      polymer which can now be analyzed at atomic detail. To achieve this, exploring
      actin's oligomerization, polymerization, polymorphism, and dynamic behavior has
      been crucial to understanding in detail how this abundant and ubiquitous protein
      can fulfill its various functions within living cells. In this review, a
      correlative view of a number of distinct aspects of actin is presented, and the
      functional implications of recent structural, biochemical, and mechanical data
      are critically evaluated. Rational analysis of these various experimental data is
      achieved using an integrated structural approach which combines intermediate
      resolution electron microscopy-based 3-D reconstructions of entire actin
      filaments with atomic resolution X-ray data of monomeric and polymeric actin.

PMID- 9245770
TI  - Isolation and characterization of spermidine nucleoids from Escherichia coli.
AB  - Nucleoids isolated from Escherichia coli at low salt concentrations in the
      presence of spermidine (Kornberg et al., Proc. Natl. Acad. Sci. USA, 71, 3189
      3193 (1974)) retain large amounts of protein and RNA and are, thus, potentially
      useful in structural and other studies. However, these preparations have neither
      been visualized nor extensively characterized with regard to their protein and
      other components. We have investigated this type of nucleoid preparation and here
      supply both light and electron microscope appearances and a description of the
      DNA-associated proteins. Light microscopy is used to follow the stages of
      nucleoid release and to demonstrate characteristically rounded nucleoids after
      chloramphenicol treatment of the cells from which the nucleoids were isolated.
      The nucleoids are "envelope-associated" particles. Electron microscopy shows an
      irregular central core that is partially covered with small, membranous vesicles.
      A significant fraction of the nucleoids have a characteristic doublet/dumbbell
      shaped appearance by light microscopy. The nucleoids contain large amounts of
      protein and RNA in addition to DNA. The DNA and RNA are rendered acid-soluble by
      very low levels of nucleases, indicating an open structure. A small group of
      proteins, including H-NS, FIS, HU, and RNA polymerase, is released from the
      particles upon enzymatic digestion of the DNA.

PMID- 9245772
TI  - Polyhedral protein cages encase synaptic vesicles and participate in their
      attachment to the active zone.
AB  - In an effort to elucidate the interactions between synaptic vesicles and the
      membrane of the active zone, we have investigated the structure of interneuronal
      asymmetric synapses in the neocortex of adult rats using thin-sectioning, freeze
      fracture, and negative staining electron microscopy. We identified three subtypes
      of spherical synaptic vesicles. Type I were agranular vesicles of 47.5 +/- 3.8 nm
      (mean SD, n = 24) in diameter usually seen aggregated in clusters in the
      presynaptic bouton. Type II synaptic vesicles were composed of a approximately 45
      nm-diameter lipid bilayer sphere encased in a cage 77 +/- 4.6 nm (mean SD, n =
      42) in diameter. The cage was composed of open-faced pentamers 20-22 nm/side
      arranged as a regular polyhedron. Type II caged vesicles were found in clusters
      at the boutons, adhered to the active zone, and were also present in axons. Type
      III synaptic vesicles appeared as electron-dense spheres 60-75 nm in diameter
      abutted to the membrane of the active zone. Clathrin-coated vesicles and pits of
      116.6 +/- 9 nm (mean SD, n = 14) in diameter were also present in both the pre-
      and postsynaptic sides. Freeze-fracture showed that some intrinsic membrane
      proteins in the active zone were arranged as pentamers exhibiting the same
      dimension of those forming cages (approximately 22 nm/side). From these data, we
      concluded that: (a) the presynaptic bouton contains a heterogeneous population of
      "caged" and "plain" synaptic vesicles and (b) type II synaptic vesicles bind to
      receptors in the active zone. Therefore, current models of transmitter release
      should take into account the substantial heterogeneity of the vesicle population
      and the binding of vesicular cages to the membrane of the active zone.

PMID- 9245773
TI  - Herbivores, the Functional Diversity of Plants Species, and the Cycling of
      Nutrients in Ecosystems
AB  - Numerous investigators have suggested that herbivores almost always increase
      rates of nutrient and energy flow through terrestrial ecosystems by returning to
      the soil fecal material and urine with faster turnover rate than shed plant
      litter. These previous theories and models always treat the producer compartment
      as a homogenous pool. Essentially, they assume that consumers feed through a
      pureed cream of vegetable soup. However, many field observations and experiments
      have shown that consumers feed selectively (i.e., in a cafeteria) and that
      consumer choice is made on the same chemical basis that determines decomposition
      rates. Plants that are preferred food sources often have higher nutrient content,
      higher growth rates, and faster decomposition rates. As consumption reduces
      dominance of these species in favor of unpreferred species with slower
      decomposition, rates of nutrient cycling and energy flow should therefore
      decline. We analyze a model in which the consumer is given a choice among
      producers that vary in nutrient uptake rates, rates of nutrient return to
      decomposers, and consumer preference, and which is parameterized for plants and
      consumers characteristic of boreal regions. In this model, in an open, well-mixed
      system with one consumer and two such producers, the nutrient/energy flow will
      not exceed that of a system without the consumer. If the consumer has a choice
      between two such producers, it must choose one plant over the other at a greater
      ratio than that between the two plants in uptake and decay rates. In contrast, in
      a closed system the consumer must be less selective to coexist with the two
      plants. The system behavior is determined by the level of nutrient return through
      the consumer and the differences between the plants in nutrient uptake rates and
      consumer preference. Species richness affects properties of this model system to
      the extent that species are functionally distinct (i.e., have different rate
      constants) in a multivariate space of life history traits (i.e., nutrient uptake
      and palatability). We suggest that the biochemical variability of plant tissues
      that simultaneously determines both consumer preference and decomposition rates
      is an essential feature of food webs that cannot be ignored. Thus, ecosystem
      models should, at minimum, consider more than one producer type with consumer
      preference.

PMID- 9245771
TI  - Stabilization of compact spermidine nucleoids from Escherichia coli under crowded
      conditions: implications for in vivo nucleoid structure.
AB  - Nucleoids from Escherichia coli were isolated in the presence of spermidine at
      low salt concentrations. The nucleoids denature at relatively low temperatures or
      salt concentrations, yielding broad slowly sedimenting zones and/or macroscopic
      aggregates upon sucrose gradient centrifugation. Denaturation is accompanied by a
      loss of a characteristically compact shape as visualized by light and electron
      microscopy. Addition of polyethylene glycol or dextran prevents these changes,
      extending the range of stability of the isolated nucleoids to temperatures and
      ionic conditions like those which commonly occur in vivo. The effects of the
      polymers are consistent with stabilization by macromolecular crowding. Enzymatic
      digestion of the nucleoid DNA primarily releases three small proteins (H-NS, FIS,
      and HU) and RNA polymerase, as well as residual lysozyme from the cell lysis
      procedure. If isolated nucleoids are extracted with elevated salt concentrations
      under crowded, stabilized conditions, two of the proteins (HU and lysozyme) are
      efficiently removed and the compact form of the nucleoids is retained. These
      extracted nucleoids maintain their compact form upon reisolation into the initial
      uncrowded low-salt medium, indicating that HU, the most common "histone-like"
      protein of E. coli, is not a necessary component for maintaining compaction in
      these preparations.

PMID- 9245774
TI  - Population Dynamics of Evolutionary Change: Demographic Parameters as Indicators
      of Fitness
AB  - I evaluated demographic parameters as indicators of fitness by calculating the
      net reproductive rate (R0), exponential rate of change (r), lifetime reproductive
      success (LRS), and Malthusian parameter (m) for nine genotypes and four
      phenotypes (two alleles at each of two independent loci) of an age-structured
      population. The given starting conditions included age-specific survival rates of
      males and females and age-specific fecundity of females for each genotype (to
      simplify the problem I presumed no differences in survivorship or fecundity of
      genotypes with the same phenotype) and the same age structure for each genotype.
      The prevailing genotype had the greatest m, but it did not have the greatest r,
      R0 , or LRS, or even the greatest survivorship of either juveniles or adults, or
      the greatest fecundity. This result indicates that m is the only correct measure
      of fitness (i.e., as a predictor of which genotype should prevail from among a
      group of genotypes) and that comparisons of r, R0 , LRS, juvenile or adult
      survival rates, or fecundity may be misleading indicators of which genotype
      should prevail (i.e., be most "fit") over time (i.e., be selected for).

PMID- 9245775
TI  - The Optimum Recombination Rate That Realizes the Fastest Evolution of a Novel
      Functional Combination of Many Genes
AB  - The effect of genetic recombination (or crossover) by sexual reproduction on the
      time until a novel set of genes performing a combined function appears, spreads,
      and becomes fixed is studied. First, we study a haploid finite population with
      many binary loci, in which only one sequence (called a functional gene set) is
      significantly advantageous over the others. The time for evolution of the
      function (Td) is defined as the mean number of generations until the advantageous
      sequence dominates in an initially random population. When the sequence diversity
      is initially stored sufficiently, the evolution time Td is roughly the product of
      the waiting time until the appearance of the advantageous sequence (creation time
      Tc) and the average number of appearances of the advantageous sequence from its
      absence until its fixation (destruction number Nd). Mutation and crossover reduce
      the former but enlarge the latter. If the mutation rate is low, there is an
      intermediate optimal rate of crossover that achieves the minimum Td. In contrast,
      if the mutation rate is sufficiently high, Td is smallest without crossover.
      Second, the breakdown of established functions by recurrent deleterious mutation
      in an infinite population is examined. The number of functional genes maintained
      decreases monotonically with the recurrent deleterious mutation rate. Thus in
      higher organisms having many functional sets of genes in the genome, the mutation
      rate must be kept very low to preserve them, and hence a high crossover rate made
      possible by sexual reproduction is important in accelerating the evolution of
      novel functional sets of genes. Implications of this long-term advantage of
      recombination in the maintenance of sexual reproduction in higher organisms are
      discussed.

PMID- 9245776
TI  - Searching for Food or Hosts: The Influence of Parasitoids Behavior on Host
      Parasitoid Dynamics
AB  - A host-parasitoid system with overlapping generations is considered. The dynamics
      of the system is described by differential equations with a control parameter
      describing the behavior of the parasitoids. The control parameter models how the
      parasitoids split their time between searching for hosts and searching for non
      host food. The choice of the control parameter is based on the assumption that
      each parasitoid maximizes the instantaneous growth rate of the number of copies
      of its genotype. It is shown that optimal individual behavior of parasitoids,
      with respect to time sharing between hosts and food searching, may have a
      stabilizing effect on the host-parasitoid dynamics.

PMID- 9245777
TI  - Ancestral Processes with Selection
AB  - In this paper, we show how to construct the genealogy of a sample of genes for a
      large class of models with selection and mutation. Each gene corresponds to a
      single locus at which there is no recombination. The genealogy of the sample is
      embedded in a graph which we call the ancestral selection graph. This graph
      contains all the information about the ancestry; it is the analogue of Kingman's
      coalescent process which arises in the case with no selection. The ancestral
      selection graph can be easily simulated and we outline an algorithm for
      simulating samples. The main goal is to analyze the ancestral selection graph and
      to compare it to Kingman's coalescent process. In the case of no mutation, we
      find that the distribution of the time to the most recent common ancestor does
      not depend on the selection coefficient and hence is the same as in the neutral
      case. When the mutation rate is positive, we give a procedure for computing the
      probability that two individuals in a sample are identical by descent and the
      Laplace transform of the time to the most recent common ancestor of a sample of
      two individuals; we evaluate the first two terms of their respective power series
      in terms of the selection coefficient. The probability of identity by descent
      depends on both the selection coefficient and the mutation rate and is different
      from the analogous expression in the neutral case. The Laplace transform does not
      have a linear correction term in the selection coefficient. We also provide a
      recursion formula that can be used to approximate the probability of a given
      sample by simulating backwards along the sample paths of the ancestral selection
      graph, a technique developed by Griffiths and Tavare (1994).

PMID- 9245778
TI  - What happens when predators do not completely consume their prey?
AB  - A mathematical model is presented for the dynamics of predator-prey interactions
      when predators do not consume prey (or clumps of prey) in their entirety. Using a
      combination of analytical and numerical methods, I demonstrate that predator
      mediated changes in the distribution of intact and partially consumed prey can
      affect the outcome of competition between predators in unexpected ways. In come
      cases, two predators can coexist on a single prey species owing to tradeoffs
      between the ability to consume prey completely and other competitive abilities.
      In other cases, predators exhibit frequency-dependent dynamics in which the first
      predator to occupy the habitat can prevent the other from invading. Conditions
      for stable coexistence usually expand if the larger predator scatters uneaten
      prey parts, if prey renewal includes both small and large items, or if the
      predator with the smaller retrieval capacity is poor at catching intact prey
      relative to the other predator.

PMID- 9245779
TI  - Variations on the intracellular transport theme: maturing cisternae and
      trafficking tubules.

PMID- 9245780
TI  - Mutational analysis of Mdm1p function in nuclear and mitochondrial inheritance.
AB  - Nuclear and mitochondrial transmission to daughter buds of Saccharomyces
      cerevisiae depends on Mdm1p, an intermediate filament-like protein localized to
      numerous punctate structures distributed throughout the yeast cell cytoplasm.
      These structures disappear and organelle inheritance is disrupted when mdm1
      mutant cells are incubated at the restrictive temperature. To characterize
      further the function of Mdm1p, new mutant mdm1 alleles that confer temperature
      sensitive growth and defects in organelle inheritance but produce stable Mdm1p
      structures were isolated. Microscopic analysis of the new mdm1 mutants revealed
      three phenotypic classes: Class I mutants showed defects in both mitochondrial
      and nuclear transmission; Class II alleles displayed defective mitochondrial
      inheritance but had no effect on nuclear movement; and Class III mutants showed
      aberrant nuclear inheritance but normal mitochondrial distribution. Class I and
      II mutants also exhibited altered mitochondrial morphology, possessing primarily
      small, round mitochondria instead of the extended tubular structures found in
      wild-type cells. Mutant mdm1 alleles affecting nuclear transmission were of two
      types: Class Ia and IIIa mutants were deficient for nuclear movement into
      daughter buds, while Class Ib and IIIb mutants displayed a complete transfer of
      all nuclear DNA into buds. The mutations defining all three allelic classes
      mapped to two distinct domains within the Mdm1p protein. Genetic crosses of yeast
      strains containing different mdm1 alleles revealed complex genetic interactions
      including intragenic suppression, synthetic phenotypes, and intragenic
      complementation. These results support a model of Mdm1p function in which a
      network comprised of multimeric assemblies of the protein mediates two distinct
      cellular processes.

PMID- 9245781
TI  - Phospholipase D stimulates release of nascent secretory vesicles from the trans
      Golgi network.
AB  - Phospholipase D (PLD) is a phospholipid hydrolyzing enzyme whose activation has
      been implicated in mediating signal transduction pathways, cell growth, and
      membrane trafficking in mammalian cells. Several laboratories have demonstrated
      that small GTP-binding proteins including ADP-ribosylation factor (ARF) can
      stimulate PLD activity in vitro and an ARF-activated PLD activity has been found
      in Golgi membranes. Since ARF-1 has also been shown to enhance release of nascent
      secretory vesicles from the TGN of endocrine cells, we hypothesized that this
      reaction occurred via PLD activation. Using a permeabilized cell system derived
      from growth hormone and prolactin-secreting pituitary GH3 cells, we demonstrate
      that immunoaffinity-purified human PLD1 stimulated nascent secretory vesicle
      budding from the TGN approximately twofold. In contrast, a similarly purified but
      enzymatically inactive mutant form of PLD1, designated Lys898Arg, had no effect
      on vesicle budding when added to the permeabilized cells. The release of nascent
      secretory vesicles from the TGN was sensitive to 1% 1-butanol, a concentration
      that inhibited PLD-catalyzed formation of phosphatidic acid. Furthermore, ARF-1
      stimulated endogenous PLD activity in Golgi membranes approximately threefold and
      this activation correlated with its enhancement of vesicle budding. Our results
      suggest that ARF regulation of PLD activity plays an important role in the
      release of nascent secretory vesicles from the TGN.

PMID- 9245782
TI  - ADP ribosylation factor 1 is required for synaptic vesicle budding in PC12 cells.
AB  - Carrier vesicle generation from donor membranes typically progresses through a
      GTP-dependent recruitment of coats to membranes. Here we explore the role of ADP
      ribosylation factor (ARF) 1, one of the GTP-binding proteins that recruit coats,
      in the production of neuroendocrine synaptic vesicles (SVs) from PC12 cell
      membranes. Brefeldin A (BFA) strongly and reversibly inhibited SV formation in
      vivo in three different PC12 cell lines expressing vesicle-associated membrane
      protein-T Antigen derivatives. Other membrane traffic events remained unaffected
      by the drug, and the BFA effects were not mimicked by drugs known to interfere
      with formation of other classes of vesicles. The involvement of ARF proteins in
      the budding of SVs was addressed in a cell-free reconstitution system (Desnos,
      C., L. Clift-O'Grady, and R.B. Kelly. 1995. J. Cell Biol. 130:1041-1049). A
      peptide spanning the effector domain of human ARF1 (2-17) and recombinant ARF1
      mutated in its GTPase activity, both inhibited the formation of SVs of the
      correct size. During in vitro incubation in the presence of the mutant ARFs, the
      labeled precursor membranes acquired different densities, suggesting that the two
      ARF mutations block at different biosynthetic steps. Cell-free SV formation in
      the presence of a high molecular weight, ARF-depleted fraction from brain cytosol
      was significantly enhanced by the addition of recombinant myristoylated native
      ARF1. Thus, the generation of SVs from PC12 cell membranes requires ARF and uses
      its GTPase activity, probably to regulate coating phenomena.

PMID- 9245783
TI  - A multispecificity syntaxin homologue, Vam3p, essential for autophagic and
      biosynthetic protein transport to the vacuole.
AB  - Protein transport in eukaryotic cells requires the selective docking and fusion
      of transport intermediates with the appropriate target membrane. t-SNARE
      molecules that are associated with distinct intracellular compartments may serve
      as receptors for transport vesicle docking and membrane fusion through
      interactions with specific v-SNARE molecules on vesicle membranes, providing the
      inherent specificity of these reactions. VAM3 encodes a 283-amino acid protein
      that shares homology with the syntaxin family of t-SNARE molecules. Polyclonal
      antiserum raised against Vam3p recognized a 35-kD protein that was associated
      with vacuolar membranes by subcellular fractionation. Null mutants of vam3
      exhibited defects in the maturation of multiple vacuolar proteins and contained
      numerous aberrant membrane-enclosed compartments. To study the primary function
      of Vam3p, a temperature-sensitive allele of vam3 was generated (vam3(tsf)). Upon
      shifting the vam3(tsf) mutant cells to nonpermissive temperature, an immediate
      block in protein transport through two distinct biosynthetic routes to the
      vacuole was observed: transport via both the carboxypeptidase Y pathway and the
      alkaline phosphatase pathway was inhibited. In addition, vam3(tsf) cells also
      exhibited defects in autophagy. Both the delivery of aminopeptidase I and the
      docking/ fusion of autophagosomes with the vacuole were defective at high
      temperature. Upon temperature shift, vam3(tsf) cells accumulated novel membrane
      compartments, including multivesicular bodies, which may represent blocked
      transport intermediates. Genetic interactions between VAM3 and a SEC1 family
      member, VPS33, suggest the two proteins may act together to direct the docking
      and/or fusion of multiple transport intermediates with the vacuole. Thus, Vam3p
      appears to function as a multispecificity receptor in heterotypic membrane
      docking and fusion reactions with the vacuole. Surprisingly, we also found that
      overexpression of the endosomal t-SNARE, Pep12p, suppressed vam3Delta mutant
      phenotypes and, likewise, overexpression of Vam3p suppressed the pep12Delta
      mutant phenotypes. This result indicated that SNAREs alone do not define the
      specificity of vesicle docking reactions.

PMID- 9245785
TI  - Regulation of calreticulin gene expression by calcium.
AB  - We have isolated and characterized a 12-kb mouse genomic DNA fragment containing
      the entire calreticulin gene and 2.14 kb of the promoter region. The mouse
      calreticulin gene consists of nine exons and eight introns, and it spans 4.2 kb
      of genomic DNA. A 1.8-kb fragment of the calreticulin promoter was subcloned into
      a reporter gene plasmid containing chloramphenicol acetyltransferase. This
      construct was then used in transient and stable transfection of NIH/ 3T3 cells.
      Treatment of transfected cells either with the Ca2+ ionophore A23187, or with the
      ER Ca2+-ATPase inhibitor thapsigargin, resulted in a five- to sevenfold increase
      of the expression of chloramphenicol acetyltransferase protein. Transactivation
      of the calreticulin promoter was also increased by fourfold in NIH/3T3 cells
      treated with bradykinin, a hormone that induces Ca2+ release from the
      intracellular Ca2+ stores. Analysis of the promoter deletion constructs revealed
      that A23187- and thapsigargin-responsive regions are confined to two regions (
      115 to -260 and -685 to -1,763) in the calreticulin promoter that contain the
      CCAAT nucleotide sequences. Northern blot analysis of cells treated with A23187,
      or with thapsigargin, revealed a fivefold increase in calreticulin mRNA levels.
      Thapsigargin also induced a fourfold increase in calreticulun protein levels.
      Importantly, we show by nuclear run-on transcription analysis that calreticulin
      gene transcription is increased in NIH/3T3 cells treated with A23187 and
      thapsigargin in vivo. This increase in gene expression required over 4 h of
      continuous incubation with the drugs and was also sensitive to treatment with
      cycloheximide, suggesting that it is dependent on protein synthesis. Changes in
      the concentration of extracellular and cytoplasmic Ca2+ did not affect the
      increased expression of the calreticulin gene. These studies suggest that stress
      response to the depletion of intracellular Ca2+ stores induces expression of the
      calreticulin gene in vitro and in vivo.

PMID- 9245784
TI  - The membrane protein alkaline phosphatase is delivered to the vacuole by a route
      that is distinct from the VPS-dependent pathway.
AB  - Membrane trafficking intermediates involved in the transport of proteins between
      the TGN and the lysosome-like vacuole in the yeast Saccharomyces cerevisiae can
      be accumulated in various vps mutants. Loss of function of Vps45p, an Sec1p-like
      protein required for the fusion of Golgi-derived transport vesicles with the
      prevacuolar/endosomal compartment (PVC), results in an accumulation of post-Golgi
      transport vesicles. Similarly, loss of VPS27 function results in an accumulation
      of the PVC since this gene is required for traffic out of this compartment. The
      vacuolar ATPase subunit Vph1p transits to the vacuole in the Golgi-derived
      transport vesicles, as defined by mutations in VPS45, and through the PVC, as
      defined by mutations in VPS27. In this study we demonstrate that, whereas VPS45
      and VPS27 are required for the vacuolar delivery of several membrane proteins,
      the vacuolar membrane protein alkaline phosphatase (ALP) reaches its final
      destination without the function of these two genes. Using a series of ALP
      derivatives, we find that the information to specify the entry of ALP into this
      alternative pathway to the vacuole is contained within its cytosolic tail, in the
      13 residues adjacent to the transmembrane domain, and loss of this sorting
      determinant results in a protein that follows the VPS-dependent pathway to the
      vacuole. Using a combination of immunofluorescence localization and pulse/chase
      immunoprecipitation analysis, we demonstrate that, in addition to ALP, the
      vacuolar syntaxin Vam3p also follows this VPS45/27-independent pathway to the
      vacuole. In addition, the function of Vam3p is required for membrane traffic
      along the VPS-independent pathway.

PMID- 9245786
TI  - A correlative analysis of actin filament assembly, structure, and dynamics.
AB  - The effect of the type of metal ion (i.e., Ca2+, Mg2+, or none) bound to the high
      affinity divalent cation binding site (HAS) of actin on filament assembly,
      structure, and dynamics was investigated in the absence and presence of the
      mushroom toxin phalloidin. In agreement with earlier reports, we found the
      polymerization reaction of G-actin into F-actin filaments to be tightly
      controlled by the type of divalent cation residing in its HAS. Moreover, novel
      polymerization data are presented indicating that LD, a dimer unproductive by
      itself, does incorporate into growing F-actin filaments. This observation
      suggests that during actin filament formation, in addition to the obligatory
      nucleation- condensation pathway involving UD, a productive filament dimer, a
      facultative, LD-based pathway is implicated whose abundance strongly depends on
      the exact polymerization conditions chosen. The "ragged" and "branched" filaments
      observed during the early stages of assembly represent a hallmark of LD
      incorporation and might be key to producing an actin meshwork capable of rapidly
      assembling and disassembling in highly motile cells. Hence, LD incorporation into
      growing actin filaments might provide an additional level of regulation of actin
      cytoskeleton dynamics. Regarding the structure and mechanical properties of the F
      actin filament at steady state, no significant correlation with the divalent
      cation residing in its HAS was found. However, compared to native filaments,
      phalloidin-stabilized filaments were stiffer and yielded subtle but significant
      structural changes. Together, our data indicate that whereas the G-actin
      conformation is tightly controlled by the divalent cation in its HAS, the F-actin
      conformation appears more robust than this variation. Hence, we conclude that the
      structure and dynamics of the Mg-F-actin moiety within the thin filament are not
      significantly modulated by the cyclic Ca2+ release as it occurs in muscle
      contraction to regulate the actomyosin interaction via troponin.

PMID- 9245787
TI  - Molecular characterization of abLIM, a novel actin-binding and double zinc finger
      protein.
AB  - Molecules that couple the actin-based cytoskeleton to intracellular signaling
      pathways are central to the processes of cellular morphogenesis and
      differentiation. We have characterized a novel protein, the actin-binding LIM
      (abLIM) protein, which could mediate such interactions between actin filaments
      and cytoplasmic targets. abLIM protein consists of a COOH-terminal cytoskeletal
      domain that is fused to an NH2-terminal domain consisting of four double zinc
      finger motifs. The cytoskeletal domain is approximately 50% identical to
      erythrocyte dematin, an actin-bundling protein of the red cell membrane skeleton,
      while the zinc finger domains conform to the LIM motif consensus sequence. In
      vitro expression studies demonstrate that abLIM protein can bind to F-actin
      through the dematin-like domain. Transcripts corresponding to three distinct
      isoforms have a widespread tissue distribution. However, a polypeptide
      corresponding to the full-length isoform is found exclusively in the retina and
      is enriched in biochemical extracts of retinal rod inner segments. abLIM protein
      also undergoes extensive phosphorylation in light-adapted retinas in vivo, and
      its developmental expression in the retina coincides with the elaboration of
      photoreceptor inner and outer segments. Based on the composite primary structure
      of abLIM protein, actin-binding capacity, potential regulation via
      phosphorylation, and isoform expression pattern, we speculate that abLIM may play
      a general role in bridging the actin-based cytoskeleton with an array of
      potential LIM protein-binding partners. The developmental time course of abLIM
      expression in the retina suggests that the retina-specific isoform may have a
      specialized role in the development or elaboration of photoreceptor inner and
      outer segments.

PMID- 9245788
TI  - Drosophila myoblast city encodes a conserved protein that is essential for
      myoblast fusion, dorsal closure, and cytoskeletal organization.
AB  - The Drosophila myoblast city (mbc) locus was previously identified on the basis
      of a defect in myoblast fusion (Rushton et al., 1995. Development [Camb.].
      121:1979-1988). We describe herein the isolation and characterization of the mbc
      gene. The mbc transcript and its encoded protein are expressed in a broad range
      of tissues, including somatic myoblasts, cardial cells, and visceral mesoderm. It
      is also expressed in the pole cells and in ectodermally derived tissues,
      including the epidermis. Consistent with this latter expression, mbc mutant
      embryos exhibit defects in dorsal closure and cytoskeletal organization in the
      migrating epidermis. Both the mesodermal and ectodermal defects are reminiscent
      of those induced by altered forms of Drac1 and suggest that mbc may function in
      the same pathway. MBC bears striking homology to human DOCK180, which interacts
      with the SH2-SH3 adapter protein Crk and may play a role in signal transduction
      from focal adhesions. Taken together, these results suggest the possibility that
      MBC is an intermediate in a signal transduction pathway from the rho/rac family
      of GTPases to events in the cytoskeleton and that this pathway may be used during
      myoblast fusion and dorsal closure.

PMID- 9245789
TI  - Dictyostelium RasG is required for normal motility and cytokinesis, but not
      growth.
AB  - RasG is the most abundant Ras protein in growing Dictyostelium cells and the
      closest relative of mammalian Ras proteins. We have generated null mutants in
      which expression of RasG is completely abolished. Unexpectedly, RasG- cells are
      able to grow at nearly wild-type rates. However, they exhibit defective cell
      movement and a wide range of defects in the control of the actin cytoskeleton,
      including a loss of cell polarity, absence of normal lamellipodia, formation of
      unusual small, punctate polymerized actin structures, and a large number of
      abnormally long filopodia. Despite their lack of polarity and abnormal
      cytoskeleton, mutant cells perform normal chemotaxis. However, rasG- cells are
      unable to perform normal cytokinesis, becoming multinucleate when grown in
      suspension culture. Taken together, these data suggest a principal role for RasG
      in coordination of cell movement and control of the cytoskeleton.

PMID- 9245790
TI  - Spindle assembly in Xenopus egg extracts: respective roles of centrosomes and
      microtubule self-organization.
AB  - In Xenopus egg extracts, spindles assembled around sperm nuclei contain a
      centrosome at each pole, while those assembled around chromatin beads do not.
      Poles can also form in the absence of chromatin, after addition of a microtubule
      stabilizing agent to extracts. Using this system, we have asked (a) how are
      spindle poles formed, and (b) how does the nucleation and organization of
      microtubules by centrosomes influence spindle assembly? We have found that poles
      are morphologically similar regardless of their origin. In all cases, microtubule
      organization into poles requires minus end-directed translocation of microtubules
      by cytoplasmic dynein, which tethers centrosomes to spindle poles. However, in
      the absence of pole formation, microtubules are still sorted into an antiparallel
      array around mitotic chromatin. Therefore, other activities in addition to dynein
      must contribute to the polarized orientation of microtubules in spindles. When
      centrosomes are present, they provide dominant sites for pole formation. Thus, in
      Xenopus egg extracts, centrosomes are not necessarily required for spindle
      assembly but can regulate the organization of microtubules into a bipolar array.

PMID- 9245791
TI  - Microtubules orient the mitotic spindle in yeast through dynein-dependent
      interactions with the cell cortex.
AB  - Proper orientation of the mitotic spindle is critical for successful cell
      division in budding yeast. To investigate the mechanism of spindle orientation,
      we used a green fluorescent protein (GFP)-tubulin fusion protein to observe
      microtubules in living yeast cells. GFP-tubulin is incorporated into
      microtubules, allowing visualization of both cytoplasmic and spindle
      microtubules, and does not interfere with normal microtubule function.
      Microtubules in yeast cells exhibit dynamic instability, although they grow and
      shrink more slowly than microtubules in animal cells. The dynamic properties of
      yeast microtubules are modulated during the cell cycle. The behavior of
      cytoplasmic microtubules revealed distinct interactions with the cell cortex that
      result in associated spindle movement and orientation. Dynein-mutant cells had
      defects in these cortical interactions, resulting in misoriented spindles. In
      addition, microtubule dynamics were altered in the absence of dynein. These
      results indicate that microtubules and dynein interact to produce dynamic
      cortical interactions, and that these interactions result in the force driving
      spindle orientation.

PMID- 9245792
TI  - A novel mammalian, mitotic spindle-associated kinase is related to yeast and fly
      chromosome segregation regulators.
AB  - We describe a novel mammalian protein kinase related to two newly identified
      yeast and fly kinases-Ipl1 and aurora, respectively-mutations in which cause
      disruption of chromosome segregation. We have designated this kinase as Ipl1- and
      aurora-related kinase 1 (IAK1). IAK1 expression in mouse fibroblasts is tightly
      regulated temporally and spatially during the cell cycle. Transcripts first
      appear at G1/S boundary, are elevated at M-phase, and disappear rapidly after
      completion of mitosis. The protein levels and kinase activity of IAK1 are also
      cell cycle regulated with a peak at M-phase. IAK1 protein has a distinct
      subcellular and temporal pattern of localization. It is first identified on the
      centrosomes immediately after the duplicated centrosomes have separated. The
      protein remains on the centrosome and the centrosome-proximal part of the spindle
      throughout mitosis and is detected weakly on midbody microtubules at telophase
      and cytokinesis. In cells recovering from nocodazole treatment and in taxol
      treated mitotic cells, IAK1 is associated with microtubule organizing centers. A
      wild-type and a mutant form of IAK1 cause mitotic spindle defects and lethality
      in ipl1 mutant yeast cells but not in wild-type cells, suggesting that IAK1
      interferes with Ipl1p function in yeast. Taken together, these data strongly
      suggest that IAK1 may have an important role in centrosome and/ or spindle
      function during chromosome segregation in mammalian cells. We suggest that IAK1
      is a new member of an emerging subfamily of the serine/threonine kinase
      superfamily. The members of this subfamily may be important regulators of
      chromosome segregation.

PMID- 9245793
TI  - Suppression of KIF2 in PC12 cells alters the distribution of a growth cone
      nonsynaptic membrane receptor and inhibits neurite extension.
AB  - In the present study, we present evidence about the cellular functions of KIF2, a
      kinesin-like superfamily member having a unique structure in that its motor
      domain is localized at the center of the molecule (Noda Y., Y. Sato-Yoshitake, S.
      Kondo, M. Nangaku, and N. Hirokawa. 1995. J. Cell Biol. 129:157-167.). Using
      subcellular fractionation techniques, isopicnic sucrose density centrifugation of
      microsomal fractions from developing rat cerebral cortex, and immunoisolation
      with KIF2 antibodies, we have now identified a type of nonsynaptic vesicle that
      associates with KIF2. This type of organelle lacks synaptic vesicle markers
      (synapsin, synaptophysin), amyloid precursor protein, GAP-43, or N-cadherin. On
      the other hand, it contains betagc, which is a novel variant of the beta subunit
      of the IGF-1 receptor, which is highly enriched in growth cone membranes. Both
      betagc and KIF2 are upregulated by NGF in PC12 cells and highly concentrated in
      growth cones of developing neurons. We have also analyzed the consequences of
      KIF2 suppression by antisense oligonucleotide treatment on nerve cell
      morphogenesis and the distribution of synaptic and nonsynaptic vesicle markers.
      KIF2 suppression results in a dramatic accumulation of betagc within the cell
      body and in its complete disappearance from growth cones; no alterations in the
      distribution of synapsin, synaptophysin, GAP-43, or amyloid percursor protein are
      detected in KIF2-suppressed neurons. Instead, all of them remained highly
      enriched at nerve terminals. KIF2 suppression also produces a dramatic inhibition
      of neurite outgrowth; this phenomenon occurs after betagc has disappeared from
      growth cones. Taken collectively, our results suggest an important role for KIF2
      in neurite extension, a phenomenon that may be related with the anterograde
      transport of a type of nonsynaptic vesicle that contains as one of its components
      a growth cone membrane receptor for IGF-1, a growth factor implicated in nerve
      cell development.

PMID- 9245794
TI  - Novel beta-secretase cleavage of beta-amyloid precursor protein in the
      endoplasmic reticulum/intermediate compartment of NT2N cells.
AB  - Previous studies have demonstrated that NT2N neurons derived from a human
      embryonal carcinoma cell line (NT2) constitutively process the endogenous wild
      type beta-amyloid precursor protein (APP) to amyloid beta peptide in an
      intracellular compartment. These studies indicate that other proteolytic
      fragments generated by intracellular processing must also be present in these
      cells. Here we show that the NH2-terminal fragment of APP generated by beta
      secretase cleavage (APPbeta) is indeed produced from the endogenous full length
      APP (APPFL). Pulse-chase studies demonstrated a precursor-product relationship
      between APPFL and APPbeta as well as intracellular and secreted APPbeta
      fragments. In addition, trypsin digestion of intact NT2N cells at 4 degrees C did
      not abolish APPbeta recovered from the cell lysates. Furthermore, the production
      of intracellular APPbeta from wild-type APP appears to be a unique characteristic
      of postmitotic neurons, since intracellular APPbeta was not detected in several
      non-neuronal cell lines. Significantly, production of APPbeta occurred even when
      APP was retained in the ER/ intermediate compartment by inhibition with brefeldin
      A, incubation at 15 degrees C, or by expression of exogenous APP bearing the
      dilysine ER retrieval motif.

PMID- 9245795
TI  - Cellular redistribution of protein tyrosine phosphatases LAR and PTPsigma by
      inducible proteolytic processing.
AB  - Most receptor-like protein tyrosine phosphatases (PTPases) display a high degree
      of homology with cell adhesion molecules in their extracellular domains. We
      studied the functional significance of processing for the receptor-like PTPases
      LAR and PTPsigma. PTPsigma biosynthesis and intracellular processing resembled
      that of the related PTPase LAR and was expressed on the cell surface as a two
      subunit complex. Both LAR and PTPsigma underwent further proteolytical processing
      upon treatment of cells with either calcium ionophore A23187 or phorbol ester
      TPA. Induction of LAR processing by TPA in 293 cells did require overexpression
      of PKCalpha. Induced proteolysis resulted in shedding of the extracellular
      domains of both PTPases. This was in agreement with the identification of a
      specific PTPsigma cleavage site between amino acids Pro821 and Ile822. Confocal
      microscopy studies identified adherens junctions and desmosomes as the
      preferential subcellular localization for both PTPases matching that of
      plakoglobin. Consistent with this observation, we found direct association of
      plakoglobin and beta-catenin with the intracellular domain of LAR in vitro. Taken
      together, these data suggested an involvement of LAR and PTPsigma in the
      regulation of cell contacts in concert with cell adhesion molecules of the
      cadherin/catenin family. After processing and shedding of the extracellular
      domain, the catalytically active intracellular portions of both PTPases were
      internalized and redistributed away from the sites of cell-cell contact,
      suggesting a mechanism that regulates the activity and target specificity of
      these PTPases. Calcium withdrawal, which led to cell contact disruption, also
      resulted in internalization but was not associated with prior proteolytic
      cleavage and shedding of the extracellular domain. We conclude that the
      subcellular localization of LAR and PTPsigma is regulated by at least two
      independent mechanisms, one of which requires the presence of their extracellular
      domains and one of which involves the presence of intact cell-cell contacts.

PMID- 9245796
TI  - Spontaneous cell fusion in macrophage cultures expressing high levels of the
      P2Z/P2X7 receptor.
AB  - Mouse and human macrophages express a plasma membrane receptor for extracellular
      ATP named P2Z/P2X7. This molecule, recently cloned, is endowed with the
      intriguing property of forming an aqueous pore that allows transmembrane fluxes
      of hydrophylic molecules of molecular weight below 900. The physiological
      function of this receptor is unknown. In a previous study we reported experiments
      suggesting that the P2Z/P2X7 receptor is involved in the formation of macrophage
      derived multinucleated giant cells (MGCs; Falzoni, S., M. Munerati, D. Ferrari,
      S. Spisani, S. Moretti, and F. Di Virgilio. 1995. J. Clin. Invest. 95:1207-
      1216). We have selected several clones of mouse J774 macrophages that are
      characterized by either high or low expression of the P2Z/P2X7 receptor and named
      these clones P2Zhyper or P2Zhypo, respectively. P2Zhyper, but not P2Zhypo, cells
      grown to confluence in culture spontaneously fuse to form MGCs. As previously
      shown for human macrophages, fusion is inhibited by the P2Z/P2X7 blocker oxidized
      ATP. MGCs die shortly after fusion through a dramatic process of cytoplasmic
      sepimentation followed by fragmentation. These observations support our previous
      hypothesis that the P2Z/P2X7 receptor is involved in macrophage fusion.

PMID- 9245799
TI  - Challenging food microbiology from a molecular perspective.

PMID- 9245797
TI  - CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial
      cells.
AB  - Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that
      is able to make normal endothelial cells unresponsive to a wide variety of
      inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived
      from it to show that this inhibition is mediated by CD36, a transmembrane
      glycoprotein found on microvascular endothelial cells. Both IgG antibodies
      against CD36 and glutathione-S-transferase-CD36 fusion proteins that contain the
      TSP-1 binding site blocked the ability of intact TSP-1 and its active peptides to
      inhibit the migration of cultured microvascular endothelial cells. In addition,
      antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 to solid
      phase CD36 and its fusion proteins, as well as to CD36-expressing cells.
      Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SM,
      oxidized (but not unoxidized) low density lipoprotein, and human collagen 1,
      mimicked TSP-1 by inhibiting the migration of human microvascular endothelial
      cells. Transfection of CD36-deficient human umbilical vein endothelial cells with
      a CD36 expression plasmid caused them to become sensitive to TSP-1 inhibition of
      their migration and tube formation. This work demonstrates that endothelial CD36,
      previously thought to be involved only in adhesion and scavenging activities, may
      be essential for the inhibition of angiogenesis by thrombospondin-1.

PMID- 9245798
TI  - Laminin 5 binds the NC-1 domain of type VII collagen.
AB  - Mutational analyses of genes that encode components of the anchoring complex
      underlying the basolateral surface of external epithelia indicate that this
      structure is the major element providing for resistance to external friction.
      Ultrastructurally, laminin 5 (alpha3beta3gamma2; a component of the anchoring
      filament) appears as a thin filament bridging the hemidesmosome with the
      anchoring fibrils. Laminin 5 binds the cell surface through hemidesmosomal
      integrin alpha6beta4. However, the interaction of laminin 5 with the anchoring
      fibril (type VII collagen) has not been elucidated. In this study we demonstrate
      that monomeric laminin 5 binds the NH2-terminal NC-1 domain of type VII collagen.
      The binding is dependent upon the native conformation of both laminin 5 and type
      VII collagen NC-1. Laminin 6 (alpha3beta1gamma1) has no detectable affinity for
      type VII collagen NC-1, indicating that the binding is mediated by the beta3
      and/or gamma2 chains of laminin 5. Approximately half of the laminin 5
      solubilized from human amnion or skin is covalently complexed with laminins 6 or
      7 (alpha3beta2gamma1). The adduction occurs between the NH2 terminus of laminin 5
      and the branch point of the short arms of laminins 6 or 7. The results are
      consistent with the presumed orientation of laminin 5, having the COOH-terminal G
      domain apposed to the hemidesmosomal integrin, and the NH2-terminal domains
      within the lamina densa. The results also support a model predicting that
      monomeric laminin 5 constitutes the anchoring filaments and bridges integrin
      alpha6beta4 with type VII collagen, and the laminin 5-6/7 complexes are present
      within the interhemidesmosomal spaces bound at least by integrin alpha3beta1
      where they may mediate basement membrane assembly or stability, but contribute
      less significantly to epithelial friction resistance.

PMID- 9245800
TI  - The Clostridium perfringens enterotoxin gene is on a transposable element in type
      A human food poisoning strains.
AB  - The Clostridium perfringens enterotoxin gene (cpe) is rarely found in naturally
      isolated strains. In human food poisoning strains, cpe is found on the
      chromosome, and is located episomally in animal isolates. Observations that the
      gene was somewhat unstable and could be gained or lost suggested that the gene
      was on a mobile element. An IS200-like element, IS1469, is almost always upstream
      of cpe. A new insertion element was identified, IS1470, a member of the IS30
      family, which is found both up-an downstream of cpe in the type A strain NCTC
      8239. PCR results confirmed that this configuration was conserved in type A human
      food poisoning strains. The enterotoxin gene was on a 6.3 kb transposon which, in
      addition to the two flanking copies of IS1470, included IS1469 and two 1 kb
      stretches, one on each side of cpe, with no open reading frames. Results
      indicated that 14 bp was copied from the genome during insertion. Details of the
      configuration of DNA in this transposon are presented, and the possible
      connection of this transposon with the movement of the enterotoxin gene is
      discussed.

PMID- 9245801
TI  - The MtrD protein of Neisseria gonorrhoeae is a member of the
      resistance/nodulation/division protein family constituting part of an efflux
      system.
AB  - The mtr (multiple transferable resistance) system of Neisseria gonorrhoeae
      mediates resistance of gonococci to structurally diverse hydrophobic agents (HAs)
      through an energy-dependent efflux process. Recently, complete or partial ORFs
      that encode membrane proteins (MtrC, MtrD, MtrE) forming an efflux pump
      responsible for removal of HAs from gonococci were identified and appeared to
      constitute a single transcriptional unit. In this study, the complete nucleotide
      sequence of the mtrD gene was determined, permitting the characterization of the
      MtrD protein. The full-length MtrD protein has a predicted molecular mass of
      nearly 114 kDa, putatively containing a 56 amino acid signal peptide. MtrD
      displays significant amino acid sequence similarity to a family of cytoplasmic
      membrane proteins, termed resistance/nodulation/division (RND) proteins, which
      function as energy-dependent transporters of antibacterial agents and secrete
      bacterial products to the extracellular fluid. The predicted topology of the MtrD
      transporter protein revealed 12 potential membrane-spanning domains, which were
      clustered within the central and C-terminal regions of the primary sequence. Loss
      of MtrD due to insertional inactivation of the mtrD gene rendered gonococci
      hypersusceptible to several structurally diverse HAs, including two fatty acids
      (capric acid and palmitic acid) and a bile salt (cholic acid), but not
      hydrophilic antibiotics such as ciprofloxacin and streptomycin. Since gonococci
      often infect mucosal sites rich in toxic fatty acids and bile salts, the
      expression of the mtr efflux system may promote growth of gonococci under hostile
      conditions encountered in vivo.

PMID- 9245802
TI  - Involvement of the gonococcal MtrE protein in the resistance of Neisseria
      gonorrhoeae to toxic hydrophobic agents.
AB  - Low-level resistance of Neisseria gonorrhoeae to toxic hydrophobic agents (HAs),
      including some antibiotics, is chromosomally mediated via the multiple
      transferable resistance (mtr) efflux system. The gene encoding the 48:3 kDa outer
      membrane protein MtrE, which is associated with the mtr phenotype, was identified
      and is homologous to export-associated outer-membrane proteins, including the
      OprM (formerly OprK) lipoprotein of Pseudomonas aeruginosa. Insertional
      inactivation of the mtrE gene in N. gonorrhoeae strain FA19 resulted in the loss
      o the outer-membrane protein, with concomitant hypersusceptibility of the mutant
      strain to a range of HAs. The properties of this mutant confirmed the role of
      MtrE in multidrug resistance mediated by an active efflux mechanism. Secondary
      structure predictions for MtrE indicated a largely hydrophilic protein with a
      single alpha-helical transmembrane region. A transposon-like element, similar to
      that found downstream of the region containing the promoters for mtrR and mtrC in
      Neisseria meningitidis, was identified 63 bp downstream of the mtrE gene.

PMID- 9245803
TI  - A spectinomycin resistance determinant from the spectinomycin producer
      Streptomyces flavopersicus.
AB  - The spectinomycin (sp) resistance determinant from Streptomyces flavopersicus was
      cloned into Streptomyces lividans using the plasmid vector pIJ699. A plasmid,
      pDGL15, with a 3.65 kb insert from S. flavopersicus conferring resistance to Sp
      was isolated. DNA sequence analysis of the 3651 1 bp DNA insert revealed four
      open reading frames (ORFs). The amino acid sequence deduced from one ORF (SpcN)
      showed a high degree of similarity to an aminoglycoside phosphotransferase (StrN)
      and from a second one (SpcR) to a regulatory protein (StrR) of the streptomycin
      biosynthesis gene cluster from S. griseus. The two other ORFs were incomplete and
      the deduced amino acid sequences showed similarities to an amidinotransferase
      encoded in the streptomycin biosynthesis gene cluster of S. griseus and to the
      transposase of IS112, respectively. Expression of the spcN gene in E. coli under
      the control of tac promoter conferred Sp resistance to the cells. An enzymic
      assay confirmed that the gene product of spcN is an ATP-dependent aminoglycoside
      phosphotransferase which phosphorylates Sp and actinamine, the aminocyclitol
      moiety of Sp.

PMID- 9245804
TI  - Conjugative transfer of tet(S) between strains of Enterococcus faecalis is
      associated with the exchange of large fragments of chromosomal DNA.
AB  - The tetracycline resistance determinant tet(S) was first detected in antibiotic
      multiresistant Listeria monocytogenes BM4210 and subsequently in strains of
      Enterococcus faecalis. Transfer of tet(S) from clinical isolate E. faecalis
      BM4242 to E. faecalis strains JH2-2 and OG1RF was found to require the presence
      in the donor strain of the 55 kb conjugative plasmid pIP825. Comparison of
      restriction endonuclease generated maps of the donor, the two recipients, and of
      four transconjugants indicated that transfer of tet(S) (i) was from chromosome to
      chromosome, (ii) resulted in the acquisition of an approximately 40 kb element in
      the same chromosomal region and (iii) was associated with the exchange of large
      chromosomal fragments. Similar observations were made following conjugal transfer
      of tet(S) from four other E. faecalis clinical isolates.

PMID- 9245805
TI  - bctA: a novel pBF4 gene necessary for conjugal transfer in Bacteroides spp.
AB  - pBF4 is a 41 kb conjugative R-plasmid that confers MLS (macrolide-lincosamide
      streptogramin B) resistance in Bacteroides spp. To identify pBF4 genes governing
      conjugation, recombinational mutagenesis using a suicide vector carrying
      fragments of the pBF4 plasmid was employed. One of the six independent insertion
      mutants of pBF4 isolated using this method was found to be conjugation-deficient.
      Nucleotide sequence analysis around the insertion site on this plasmid revealed a
      2.8 kb ORF that encoded a putative 110 kDa protein. A corresponding protein was
      observed when a 12 kb DNA fragment containing this ORF was used to program an in
      vitro transcription-translation system. Both the ORF and the predicted protein
      were novel when compared to available database sequences. This gene was
      designated bctA (Bacteroides conjugal transfer). Polyclonal rabbit antibodies
      that recognized a sub-sequence polypeptide of BctA reacted with a 55 kDa protein
      in Western blot analysis using a total protein extract from Bacteroides fragilis
      containing pBF4. The protein was not present in a B. fragilis strain containing
      the conjugation-deficient insertion mutant of pBF4. The 55 kDa protein was
      associated with the membrane fraction of B. fragilis. Although the cellular and
      biochemical basis of bctA-promoted conjugation remains unknown, this work
      demonstrates the existence of a heretofore unrecognized gene in bacterial
      conjugation, and the mutagenesis system used provides the means to isolate and
      characterize other genes involved in conjugal transfer in Bacteroides spp.

PMID- 9245806
TI  - Divergence and conservation of the partitioning and global regulation functions
      in the central control region of the IncP plasmids RK2 and R751.
AB  - The central control region (Ctl) of IncP plasmids is associated with two
      phenotypes: the coordinate expression of replication and transfer genes; and the
      ability to increase the segregational stability of a low-copy number test
      plasmid. This region of the IncP beta plasmid R751 shows significant sequence
      divergence from the IncP alpha plasmid RK2 sequence, and two genes, korF and
      korG, present in the IncP alpha region are missing in the IncP beta Ctl. In other
      respects the organization of the Ctl is basically the same. Although the two key
      global regulatory genes korA and korB are highly conserved, studies on their
      ability to repress transcription from a variety of IncP alpha and IncP beta
      plasmid promoters suggest differences in operator recognition by KorA and synergy
      with other repressors. The products of kfrA, upf54.8 and upf54.4 genes are
      conserved; KfrA shows least conservation and, while retaining the ability to act
      as a transcriptional repressor, appears to have completely different DNA-binding
      specificity. The genes required for the plasmid segregational stabilization
      (partitioning) phenotype--incC, korB and the korB operator OB3--are conserved and
      contribute to a more efficient plasmid stabilization than the IncP alpha
      equivalents. This may indicate that the Ctl plays an especially important role in
      partitioning of IncP beta plasmids, since they lack the second stability region
      (parlmrs) found in IncP alpha plasmids.

PMID- 9245807
TI  - Alanyl-tRNA synthetase gene of the extreme acidophilic chemolithoautotrophic
      Thiobacillus ferrooxidans is highly homologous to alaS genes from all living
      kingdoms but cannot be transcribed from its promoter in Escherichia coli.
AB  - The alaS gene of Thiobacillus ferrooxidans has been cloned and sequenced and its
      expression in Escherichia coli and T. ferrooxidans analysed. The same genomic
      organization to that in E. coli (recA-recX-alaS) has been found in T.
      ferrooxidans. The recA and alaS genes cannot be transcribed from their own
      promoters in E. coli. In addition to the well-known homology at the protein level
      between AlaS proteins from various organisms, a strong homology was found between
      all the known alaS genes from bacteria, archaea and eucarya. Two regions, one of
      which corresponds to the catalytic core, are particularly well-conserved at the
      nucleotide sequence level, a possible indication of strong constraints during
      evolution on these parts of the genes.

PMID- 9245808
TI  - The pyruvate dehydrogenase complex of the chemolithoautotrophic bacterium
      Thiobacillus ferrooxidans has an unusual E2-E3 subunit fusion.
AB  - The genes encoding pyruvate dehydrogenase (PDH) of Thiobacillus ferrooxidans were
      previously located by cloning and sequence analysis of the region upstream of the
      genes encoding the citrate synthase and gamma glutamylcysteine synthetase genes.
      The pdh genes of T. ferrooxidans were able to complement an Escherichia coli aroP
      lpd mutant for growth on minimal medium lacking acetate, indicating that the T.
      ferrooxidans PDH complex was functional in E. coli. The predicted amino acid
      sequence of the T. ferrooxidans PDH complex contained three ORFs. The first ORF
      encoded a 36.7 kDa homologue of the PDH complex E1 alpha subunit, the second ORF
      a 37.4 kDa E1 beta subunit and the third ORF an unusual 102 kDa fusion of the E2
      and E3 subunits. In spite of T. ferrooxidans being a Gram-negative bacterium, its
      PDH complex had more features in common with Gram-positive bacteria and
      eukaryotes.

PMID- 9245809
TI  - The cydR gene product, required for regulation of cytochrome bd expression in the
      obligate aerobe Azotobacter vinelandii, is an Fnr-like protein.
AB  - The cytochrome bd complex in the obligately aerobic diazotroph Azotobacter
      vinelandii is an oxidase, which, in vivo, has a low affinity for oxygen and is
      required for respiratory protection of nitrogenase. Mutations caused by insertion
      of Tn5-B20 upstream of the structural genes (cydAB) for cytochrome bd result in
      over-expression of this oxidase and, for unexplained reasons, inability of the
      organism to grow microaerobically. Cloning and sequencing of this upstream region
      revealed a gene, cydR. The deduced amino acid sequence of CydR indicates that it
      is a new member of the Fnr Class of regulators and that it represses cydAB
      expression. Refined mapping data for three insertions in cydR are presented. The
      cloned cydR gene complemented anaerobic growth of Escherichia coli fnr mutants
      and strongly enhanced expression of a narG-lacZ fusion in an E. coli fnr mutant.

PMID- 9245810
TI  - Regulation of the TCA cycle and the general amino acid permease by overflow
      metabolism in Rhizobium leguminosarum.
AB  - Mutants of Rhizobium leguminosarum were selected that were altered in the uptake
      activity of the general amino acid permease (Aap). The main class of mutant maps
      to sucA and sucD, which are part of a gene cluster mdh-sucCDAB, which codes for
      malate dehydrogenase (mdh), succinyl-CoA synthetase (sucCD) and components of the
      2-oxoglutarate dehydrogenase complex (sucAB). Mutation of either sucC or sucD
      prevents expression of 2-oxoglutarate dehydrogenase (sucAB). Conversely, mutation
      of sucA or sucB results in much higher levels of succinyl-CoA synthetase and
      malate dehydrogenase activity. These results suggest that the genes mdh-sucCDAB
      may constitute an operon. suc mutants, unlike the wild-type, excrete large
      quantities of glutamate and 2-oxoglutarate. Concomitant with mutation of sucA or
      sucD, the intracellular concentration of glutamate but no 2-oxoglutarate was
      highly elevated, suggesting that 2-oxoglutarate normally feeds into the glutamate
      pool. Elevation of the intracellular glutamate pool appeared to be coupled to
      glutamate excretion as part of an overflow pathway for regulation of the TCA
      cycle. Amino acid uptake via the Aap of R. leguminosarum was strongly inhibited
      in the suc mutants, even though the transcription level of the aap operon was the
      same as the wild-type. This is consistent with previous observations that the
      Aap, which influences glutamate excretion in R. leguminosarum, has uptake
      inhibited when excretion occurs. Another class of mutant impaired in uptake by
      the Aap is mutated in polyhydroxybutyrate synthase (phaC). Mutants of succinyl
      CoA synthetase (sucD) or 2-oxoglutarate dehydrogenase (sucA) form ineffective
      nodules. However, mutants of aap, which are unable to grow on glutamate as a
      carbon source in laboratory culture, show wild-type levels of nitrogen fixation.
      This indicates that glutamate is not an important carbon and energy source in the
      bacteroid. Instead glutamate synthesis, like polyhydroxybutyrate synthesis,
      appears to be a sink for carbon and reductant, formed when the 2-oxoglutarate
      dehydrogenase complex is blocked. This is in accord with previous observations
      that bacteroids synthesize high concentrations of glutamate. Overall the data
      show that the TCA cycle in R. leguminosarum is regulated by amino acid excretion
      and polyhydroxybutyrate biosynthesis which act as overflow pathways for excess
      carbon and reductant.

PMID- 9245811
TI  - A Pneumocystis carinii multi-gene family with homology to subtilisin-like serine
      proteases.
AB  - Copies of multi-gene family, named PRT1 (protease 1), encoding a subtilisin-like
      serine protease were cloned from the opportunistic fungal pathogen Pneumocystis
      carinii. Comparison of the nucleotide sequence of a genomic clone and a cDNA
      clone of PRT1 from P. carinii f. sp. carinii revealed the presence of seven short
      introns. Several different domains were predicted from the deduced amino acid
      sequence: an N-terminal hydrophobic signal sequence, a pro-domain, a subtilisin
      like catalytic domain, a P-domain (essential for proteolytic activity), a proline
      rich domain, a serine/threonine-rich domain and a C-terminal hydrophobic domain.
      The catalytic domain showed high homology to other eukaryotic subtilisin-like
      serine proteases and possessed the three essential residues of the catalytic
      active site. Karyotypic analysis showed that PRT1 was a multi-gene family, copies
      of which were present on all but one of the P. carinii f. sp. carinii
      chromosomes. The different copies of the PRT1 genes showed nucleotide sequence
      heterogeneity, the highest level of divergence being in the proline-rich domain,
      which varied in both length and composition. Some copies of PRT1 were contiguous
      with genes encoding the P. carinii major surface glycoprotein.

PMID- 9245812
TI  - Cloning and disruption of the ornithine decarboxylase gene of Ustilago maydis:
      evidence for a role of polyamines in its dimorphic transition.
AB  - The gene encoding ornithine decarboxylase (ODC) from Ustilago maydis was cloned.
      A conserved PCR product amplified from U. maydis DNA was synthesized and used to
      screen a genomic library of the fungus. Alignment of its deduced protein sequence
      with those of other cloned ODCs showed a high degree of homology. Gene
      replacement was obtained by removal of a central part of the gene and insertion
      of the hygromycin resistance cassette. The null mutant thus obtained displayed no
      ODC activity and behaved as a polyamine auxotroph. This result is evidence that a
      single ODC gene exists in the fungus, and that U. maydis utilizes the ODC pathway
      as the only mechanism for polyamine biosynthesis. When grown in polyamine
      containing media, the null mutant accumulated a polyamine pool which further
      sustained its normal rate of growth in polyamine-free media for approximately 12
      16 h. When putrescine concentrations lower than 0.5 mM were employed, the mutant
      grew at a normal rate but was unable to engage in the dimorphic transition. Under
      conditions favourable for mycelial growth, the mutant grew with a yeast-like
      morphology in liquid media, and formed smooth colonies consisting of yeast cells
      on solid media. Reversion to normal dimorphic phenotype required high
      concentrations of putrescine or spermidine. These results are evidence that
      concentrations of polyamines higher than those necessary to sustain vegetative
      growth are required for the dimorphic transition in U. maydis.

PMID- 9245813
TI  - The Aspergillus fumigatus mepB gene encodes an 82 kDa intracellular
      metalloproteinase structurally related to mammalian thimet oligopeptidases.
AB  - Aspergillus fumigatus produces an 82 kDa intracellular metalloproteinase that
      hydrolyses the Pz-peptide, 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-Arg, a
      typical substrate of members of the thimet oligopeptidase family which is
      ubiquitously distributed across animal species. The A. fumigatus mepB gene
      encoding this 82 kDa metalloproteinase was cloned and sequenced. Analysis of the
      deduced amino acid sequence of mepB showed that the MepB protein is a cytosolic
      zinc metalloproteinase of the thimet oligopeptidase family (M3) and as such is
      probably involved in the intracellular degradation of small peptides. An A.
      fumigatus mutant that lacks the MepB Pz-peptidolytic activity was constructed by
      gene disruption at the mepB locus. Analysis of this mutant did not reveal any
      detectable phenotype.

PMID- 9245814
TI  - Monoclonal antibodies as probes for fungal wall structure during morphogenesis.
AB  - Three monoclonal antibodies (mAbs), S4D1, S3B3 and S1E5, were produced from
      hybridoma cell lines raised from mice immunized with hyphal walls of Neurospora
      crassa and one (Pax-1) from mice immunized with hyphal walls of Paxillus
      involutus. In immunofluorescence studies, the three N. crassa mAbs recognized
      epitopes with different patterns of distribution at the hyphal surface of N.
      crassa. S4D1 recognized an epitope which was present on the surface of both
      conidia and hyphae; S3B3 recognized an epitope seen only at the ends of conidia
      or in the septal region of hyphae and conidial chains; and S1E5 recognized an
      epitope present on the surface of hyphae, but not on mature conidia. mAb Pax-1
      reacted with hyphal wall fragments of Pax. involutus and with N. crassa conidia
      in a similar way to S3B3. S4D1 reacted with an epitope found in 1,3-alpha-glycan
      preparations from hyphal walls of different fungi. The surface distribution of
      this epitope varied: it was found on the surface of both conidia and hyphae of N.
      crassa and Aspergillus nidulans, on the basidiospore surface only of Amanita
      muscaria, and on the hyphae but not the conidia of Penicillium chrysogenum.
      Immunogold studies revealed that the epitope was present throughout the wall of
      conidia and hyphae of N. crassa. mAbs S3B3, S1E5 and Pax-1 also reacted with
      other fungi: for example Pax-1 cross-reacted with all fungi tested except for a
      member of the Zygomycota. Immunogold studies revealed that epitopes of these
      three mAbs were present within the inner layers of the walls of conidia and
      hyphae of N. crassa.

PMID- 9245815
TI  - Regulation of the inducible acetamidase gene of Mycobacterium smegmatis.
AB  - The inducible acetamidase of Mycobacterium smegmatis NCTC 8159 is expressed at
      high levels in the presence of a suitable inducer, such as acetamide. The gene
      and 1.5 kb of upstream sequence had previously been sequenced. A further 1.4 kb
      of upstream sequence has now been determined, containing an additional ORF on the
      opposite strand to the acetamidase gene. This ORF has significant homologies to
      genes encoding regulatory proteins involved in amidase expression in other
      organisms. Restriction fragments from the 4 kb region were subcloned into a
      promoter-probe shuttle vector to locate the approximate region of the acetamidase
      promoter and investigate the mechanism of regulation. An inducible promoter was
      found to lie in the 1.4 kb region situated 1.5 kb upstream from the acetamidase
      coding region. Expression of the acetamidase was studied at the protein and mRNA
      levels. Using immunoblotting, induction of the enzyme was demonstrated in minimal
      medium containing succinate plus acetamide, but not in a richer medium (Lemco
      broth) plus acetamide, confirming that regulation of acetamidase expression is
      mediated by both positive and negative control elements. After induction by
      acetamide, an increase above basal level could be detected after 1 h for both
      protein levels (using ELISA) and mRNA levels (using Northern blot analysis),
      indicating that control of expression is at the mRNA level. The size of the mRNA
      transcript detected was approximately 1.2 kb, the size of the acetamidase coding
      region. Since no promoter was identified immediately upstream of the coding
      region, this raises the possibility that a larger, primary transcript (possibly
      polycistronic) is cleaved to produce a stable form encoding the acetamidase
      protein.

PMID- 9245816
TI  - Molecular characterization of the restriction endonuclease gene (scrFIR)
      associated with the ScrFI restriction/modification system from Lactococcus lactis
      subsp. cremoris UC503.
AB  - The nucleotide sequence of the chromosomally encoded type II ScrFI
      restriction/modification system from Lactococcus lactis subsp. cremoris UC503 was
      completed. The ScrFI restriction endonuclease (ENase) has previously been shown
      to specifically recognize 5' CCNGG 3' sites, cleaving after the second cytosine
      and the degenerate central base. The ENase gene (scrFIR; 362 bp) was located
      between, and co-directionally transcribed with, two formerly characterized 5
      methylcytosine methyltransferase genes, which encodes proteins that independently
      confer protection against ScrFI digestion. scrFIR codes for a protein of 272
      amino acids with a predicted molecular mass of 31470 Da, which agrees favourably
      with a previously estimated molecular mass of 34 kDa for this enzymes. The
      deduced sequence of this protein did not show any significant homology with known
      protein sequences, including the isoschizomeric Ssoll ENase from Shigella sonnei.
      The ENase gene was cloned and expressed in Escherichia coli and Lactococcus;
      however, no in vivo restriction of phage was observed, suggesting that expression
      of the ENase gene may be repressed, or that the appropriate expression signals
      may be absent in the cloned constructs. The ability of ScrFI to cleave non
      canonically modified 5' CCNGG 3' sequences suggested that some ScrFI sites may
      require complex modifications to fully impair digestion by this enzyme.

PMID- 9245818
TI  - Role of the colicin A lysis protein in the expression of the colicin A operon.
AB  - The involvement of the cal gene, which encodes the colicin A lysis protein, in
      the expression of the colicin A operon is demonstrated. Colicin A synthesis by
      Escherichia coli was studied at various temperatures in cells containing either
      the wild-type colicin A operon or the colicin A operon with the cal gene deleted.
      The amount of colicin A produced was lower in cells containing the colicin A
      operon devoid of the cal gene than in wild-type cells. In cells treated with the
      antibiotic globomycin, the synthesis of colicin A was blocked in null cal mutants
      at all temperatures. It was blocked only at low temperature in cells containing
      the wild-type colicin A operon, but not in cells subjected to heat shock or azide
      treatment. The cal gene product may be an activator of colicin A expression and
      of its own expression. An unidentified product, possibly a heat-shock protein,
      may also be involved and could complement the cal gene product in some
      situations.

PMID- 9245817
TI  - Enterocin B, a new bacteriocin from Enterococcus faecium T136 which can act
      synergistically with enterocin A.
AB  - The strain Enterococcus faecium T136 produces two bacteriocins, enterocin A, a
      member of the pediocin family of bacteriocins, and a new bacteriocin termed
      enterocin B. The N-terminal amino acid sequences of enterocins A and B were
      determined, and the gene encoding enterocin B was sequenced. The primary
      translation product was a 71 aa peptide containing a leader peptide of the double
      glycine type which is cleaved off to give mature enterocin B of 53 aa. Enterocin
      B does not belong to the pediocin family of bacteriocins and shows strong
      homology to carnobacteriocin A. However, sequence similarities in their leader
      peptides and C-termini suggest that enterocin B and carnobacteriocin A are
      related to bacteriocins of the pediocin family. Enterocins A and B had only
      slightly different inhibitory spectra, and both were active against a wide range
      of Gram-positive bacteria, including listeriae, staphylococci and most lactic
      acid bacteria tested. Both had bactericidal activities, but survival at a
      frequency of 10(-4)-10(-2) was observed when sensitive cultures were exposed to
      either bacteriocin. The number of survivors was drastically reduced when a
      mixture of the two bacteriocins was added to the cells.

PMID- 9245819
TI  - An outer-membrane porin inducible by short-chain amides and urea in the
      methylotrophic bacterium Methylophilus methylotrophus.
AB  - The fmdA and fmdB genes encoding formamidase and a putative regulatory protein,
      respectively, from the methylotrophic bacterium Methylophilus methylotrophus were
      recloned with additional flanking DNA (pSW1). fmdC, encoding a weakly hydrophilic
      protein containing an N-terminal signal sequence, was identified upstream of
      fmdAB. The derived amino acid sequence of mature FmdC (M(r) 39204) showed that it
      was rich in beta-sheet and aromatic amino acids, and exhibited significant
      similarities to several outer-membrane porins from other bacteria. Cell
      fractionation studies showed that the protein was located in the outer membrane.
      Mature FmdC was purified and shown to consist of a single type of subunit (M(r)
      40,000) with the predicted N-terminal amino acid sequence (GATISF-). SDS-PAGE and
      Western blotting of cells grown in continuous culture under various conditions
      showed that mature FmdC was induced by formamide, acetamide and urea, repressed
      by excess ammonia, and over-expressed during prolonged growth under formamide
      limitation. It is concluded that mature FmdC is a porin involved in the transport
      of short-chain amides and urea through the outer membrane of M. methylotrophus
      under conditions where these nitrogen sources are present at very low
      concentration.

PMID- 9245820
TI  - Tn5-induced lipopolysaccharide mutations in Bordetella pertussis that affect
      outer membrane function.
AB  - An LPSB-specific mAb was used to screen for ten Tn5 insertion mutants of
      Bordetella pertussis which have LPS which is phenotypically distinct from either
      wild-type LPSAB or LPSB. Silver-strained SDS-PAGE gels showed nine different LPS
      phenotypes, six of which contain two clinically undocumented LPS bands,
      designated IntA and IntB based on their proximity to the LPSA and LPSB bands,
      respectively. Binding assays with LPSA- and LPSB-specific mAbs established
      changes in epitope exposure for the various mutant LPS, both in cell-free form
      and as presented on the surface of whole cells. The possible involvement of a
      number of genes, both structural and regulatory, was indicated in production of
      the altered phenotypes. PFGE and Southern blotting showed that the Tn5 inserts of
      seven mutants mapped to a region of the B. pertussis chromosome shown previously
      to encode the bpl gene products of LPS biosynthesis. Mutants MLT3, MLT5 and MLT8,
      however, mapped to distinctly different parts of the chromosome. In addition,
      mutants MLT2 and MLT3 contributed to an accelerated frequency in the appearance
      of avirulent phase organisms despite their Tn5 inserts being over 1000 bp from
      the bvglASR locus. The alterations in LPS structure in the mutants changed their
      reactivity to strain-specific mAbs and their sensitivity to hydrophobic and
      hydrophilic antibiotics.

PMID- 9245821
TI  - The Staphylococcus aureus allelic genetic loci for serotype 5 and 8 capsule
      expression contain the type-specific genes flanked by common genes.
AB  - The nucleotide sequences of two gene clusters, cap5 and cap8, involved in the
      synthesis of Staphylococcus aureus type 5 and type 8 capsular polysaccharides
      (CPs), respectively were determined. Each gene cluster contained 16 ORFs, which
      were named cap5A through cap5P for type 5 CP and cap8A through cap8P for type 8
      CP. The cap5 and cap8 loci were allelic and were mapped to the SmaI-G fragment in
      the standard SmaI map of Staph. aureus strain NCTC 8325. The predicted gene
      products of cap5A through cap5G and cap5L through cap5P are essentially identical
      to those of cap8A through cap8G and cap8L through cap8P, respectively, with very
      few amino acid substitutions. Four ORFs located in the central region of each
      locus are type-specific. A comparison of the predicted amino acid sequences of
      cap5 and cap8 with sequences found in the databases allowed tentative assignment
      of functions to 15 of the 16 ORFs. The majority of the capsule genes are likely
      to be involved in amino sugar synthesis; the remainder are likely to be involved
      in sugar transfer, capsule chain-length regulation, polymerization and transport.

PMID- 9245822
TI  - The effects of adherence to silicone surfaces on antibiotic susceptibility in
      Staphylococcus aureus.
AB  - Sensitivity of Staphylococcus aureus to the antibiotics tetracycline,
      benzylpenicillin and vancomycin was found to decrease by 2-10 fold when cells
      were grown adherent to silicone catheter surfaces. Sensitivity to rifampicin and
      fusidic acid was not significantly altered in adherent cells. Susceptibility
      further decreased with increased adherence time prior to antibiotic challenge.
      The resistance observed was not genotypic, or due to the presence of a
      specialized subpopulation of bacteria, as it disappeared when the bacteria were
      removed from the catheter, subcultured and retested. Also, adherent bacteria were
      found to grow more slowly than bacteria growing planktonically. It is concluded
      that the decrease in antibiotic susceptibility of adherent bacteria is a function
      of the physiological status of the individual cells rather than a function of
      biofilm formation or slime production. The decrease in growth rate of the
      adherent bacteria is a result of the adherence process rather than a result of
      nutrient depletion. The decrease in growth rate is implicated, but is not the
      sole factor, in the decreased antibiotic susceptibility of adherent bacteria.

PMID- 9245823
TI  - Anaerobic pathways of glycerol dissimilation by Enterobacter agglomerans CNCM
      1210: limitations and regulations.
AB  - Continuous cultures of Enterobacter agglomerans CNCM 1210 were performed under
      regulated pH conditions (pH 7.0) with glycerol or glucose (20 g l-1) as carbon
      source. Cultures grown on glucose produced mainly acetate, ethanol and formate.
      In contrast, 1,3-propanediol (PPD) was the main product with glycerol. The carbon
      flow distribution at branching metabolic points was investigated. Higher PPD
      yields with increased dilution rate were correlated with an important increase in
      the relative ratio of glycerol dehydratase to glycerol dehydrogenase.
      Determination of intracellular triose-phosphate and fructose 1,6-biphosphate
      concentrations demonstrated that glyceraldehyde-3-phosphate dehydrogenase is the
      limiting step in glycerol dissimilation. At the pyruvate branching point,
      pyruvate dehydrogenase (PDH) activity was systematically detected. The pyruvate
      flow shifted to PDH is suspected to represent up to 22% of the acetyl-CoA formed.
      In addition, this enzyme pattern combined with the enhanced in vivo lactate
      dehydrogenase activity at high growth rates, was correlated with a decrease in
      the pyruvate formate-lyase activity. A regulation of this latter enzyme by the
      accumulation of triose-phosphate is suspected.

PMID- 9245824
TI  - Medium- and long-chain fatty acid uptake and utilization by Streptomyces
      coelicolor A3(2): first characterization of a gram-positive bacterial system.
AB  - The first characterization of fatty acid uptake in a Gram-positive bacterium is
      reported. Streptomyces coelicolor A3(2) utilizes fatty acids of different chain
      length (C4-C18) as sole carbon and energy sources. In vivo beta-oxidation studies
      and the assay of two enzymes of the beta-oxidation cycle proved that fatty acid
      degradation is constitutive in this micro-organism. Uptake of the medium-chain
      fatty acid octanoate showed the characteristics of simple diffusion, whereas the
      uptake of palmitate, a long-chain fatty acid, occurred by both simple diffusion
      and active transport. After correcting for non-mediated transport, palmitate
      uptake measured over a wide range of concentrations followed Michaelis-Menten
      kinetics. The apparent Km for palmitate was 97.8 microM and the Vmax was 19.3
      nmol min-1 (mg protein)-1. Competition experiments showed specificity of the
      mediated transport component for long-chain fatty acids (> C10). Metabolic
      inhibitors such as oligomycin, NaF and vanadate, and the ionophores gramicidin
      and carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited palmitate uptake to
      different degrees, consistent with the existence of an active transport
      mechanism. Uptake rates measured at different pH values indicated that both the
      ionized and the unionized forms of octanoate crossed the cytoplasmic membrane by
      simple diffusion. Palmitate in its ionized form appears to be transported by an
      active mechanism, whereas the unionized molecule diffuses through the membrane.
      When present in the medium, glucose stimulated the degradation of long-chain
      fatty acids by increasing the rate of uptake and the level of acyl-CoA
      synthetase.

PMID- 9245825
TI  - Mitogenic factor secreted by Streptococcus pyogenes is a heat-stable nuclease
      requiring His122 for activity.
AB  - The gene encoding a mitogenic factor, termed MF, was cloned from Streptococcus
      pyogenes and the recombinant MF was overexpressed in Escherichia coli. Both the
      natural and recombinant MF had heat-resistant nuclease activity. The nuclease
      activity of MF was characterized using the recombinant protein. MF showed
      endonuclease activity, digesting ssDNA, dsDNA and tRNA. The optimal pH for the
      DNase activity of MF was 9.5. The DNase activity was enhanced approximately
      tenfold by the simultaneous presence of two divalent cations, Mg2+ and Ca2+,
      compared to either alone and was inhibited by EDTA or NaCl. The heat stability of
      MF was biphasic; the DNase activity was heat-stable from 0 to 50 degrees C over
      80 degrees C but very unstable at around 60 degrees C. DNA digested by MF
      possessed 5'-phosphorylated and 3'-hydroxylated termini, identical to those
      obtained by digestion of DNA by pancreatic deoxyribonuclease I. A mutant clone
      revealed that His122 was a residue essential to the nuclease activity.

PMID- 9245826
TI  - Protein kinase Sck1 is involved in trehalase activation by glucose and nitrogen
      source in the fission yeast Schizosaccharomyces pombe.
AB  - Trehalase activity is markedly enhanced upon addition of glucose and a nitrogen
      source to cells of the fission yeast Schizosaccharomyces pombe. This increase
      corresponds to a post-translational activation of the enzyme, which is controlled
      by cAMP-dependent and cAMP-independent pathways. Recent work has shown that
      overexpression of SCK1 in Schiz. pombe is able to suppress mutations that result
      in reduced Pka1 (cAMP-dependent protein kinase A activity, suggesting that Sck1
      (suppressor of loss of cAMP-dependent protein kinase) might be a functional
      analogue of Pka1 in the fission yeast. Here, an analysis of the possible role of
      Sck1 in the activation of trehalase triggered by glucose and a nitrogen source is
      reported in cells that were deficient in either Pka1, Sck1 or both protein
      kinases. The results showed that, except in repressed cells, Sck1 probably
      mediates a cAMP-independent activation of trehalase following the signal(s)
      triggered by glucose and the nitrogen source. The absence of functional Sck1 in
      depressed cells renders trehalase insensitive to activation by glucose and the
      nitrogen source even in the presence of Pka1, indicating that the Sck1-dependent,
      cAMP-independent pathway is the main signalling pathway controlling trehalase
      activation under derepression conditions. It is proposed that, during the
      activation of trehalase induced by glucose or a nitrogen source, the cAMP-Pka1
      activation pathway previously characterized is to some extent parallel to this
      newly described one which includes Sck1 as phosphorylating enzyme. Neither of
      these two pathways, however, plays a key role in the heat-induced increase in
      trehalase activity.

PMID- 9245827
TI  - Reduction of ATPase activity accompanied by photodecomposition of ergosterol by
      near-UV irradiation in plasma membranes prepared from Saccharomyces cerevisiae.
AB  - When plasma membranes prepared from the yeast Saccharomyces cerevisiae were
      exposed to near-UV radiation, photodecomposition of ergosterol and reduction of
      ATPase-activity occurred simultaneously. The Vmax for ATPase activity decreased
      markedly with increasing near-UV dosage while the Km value remained constant.
      When ATPase solubilized from the plasma membrane was exposed to near-UV, the
      activity remained constant irrespective of dosage, indicating that the ATPase
      molecule itself was not damaged by near-UV irradiation. The relationship between
      content of ergosterol and ATPase activity was examined using liposomes
      constructed with lipids extracted from the membrane. Maximum activity of ATPase
      was seen at 5% ergosterol in liposomes; this activity was 2.5 times greater than
      that in liposomes without ergosterol. Activity of ATPase bound to liposomes with
      5% ergosterol was reduced after near-UV irradiation, while the activity remained
      unchanged in the case of the liposomes without ergosterol. Fluidity of the
      liposomes with 5% ergosterol also decreased with increasing near-UV dosage.
      Dosage-response curves for reduction of ATPase activity and for decrease in
      fluidity were similar to that for photodecomposition of ergosterol. These results
      suggested that the reduction of ATPase activity in the membrane by near-UV
      irradiation was not caused by photochemical degradation of the primary structure
      of the ATPase molecule, but was attributable to conformational change resulting
      from an alteration in the higher-order structure of the membrane due to
      photochemical decomposition of ergosterol.

PMID- 9245828
TI  - The properties and localization of Saprolegnia monoica chitin synthase differ
      from those of other fungi.
AB  - The presence of non-fibrillar alpha-chitin in cellulosic fungi (class Oomycetes)
      poses intriguing questions as to its role, subcellular localization and
      evolutionary significance. Previous studies reported on the similarity of chitin
      synthase from Saprolegnia monoica with that of other fungi. The present work
      describes important dissimilarities. There was no evidence that the chitin
      synthase of S. monoica was present in small low-density vesicles (chitosomes).
      Chitin synthase sedimented with membranous components of high specific gravity
      (sp. gr. 1.177) that could be partially but distinctly separated from membranes
      harbouring most of the 1,3-beta-glucan synthase in the cell (sp. gr. 1.158). In
      contrast to other fungi, the chitin synthase from S. monoica was greatly
      stimulated by digitonin: both membrane-bound and dissociated chitin synthase
      showed little activity in the absence of digitonin. As in other fungi, the chitin
      synthase from S. monoica was solubilized by digitonin and remained zymogenic
      after dissociation. However, unlike the enzyme from other fungi, the solubilized
      chitin synthase of S. monoica had a lower sedimentation coefficient, was not
      stimulated by phospholipids and was not inhibited by high concentrations of
      digitonin. Unlike the enzyme from Mucor rouxii, the solubilized chitin synthase
      from S. monoica did not bind to a cation exchanger. The enzyme was partially
      purified by four-step scheme that included sucrose density-gradient
      centrifugation, a single passage through a strong anion exchanger and two
      consecutive passages through a weak anion exchanger. The final preparation
      contained five to seven polypeptide bands that cochromatographed with the chitin
      synthase activity, some of which may be part of a presumed chitin synthase
      macromolecular complex.

PMID- 9245829
TI  - A cell-associated protein complex of Porphyromonas gingivalis W50 composed of Arg
      and Lys-specific cysteine proteinases and adhesins.
AB  - Porphyromonas gingivalis has been associated with the development of adult
      periodontitis and cysteine proteinases with trypsin-like specificity have been
      implicated as major virulence factors. We have extracted the major cell
      associated trypsin-like proteolytic activity of P. gingivalis W50 using mild
      sonication. Anion-exchange and gel-filtration FPLC of the sonicate revealed that
      Arg- and Lys-specific proteinase activity was associated with a 300 kDa complex
      which could be dissociated into seven bands (48, 45, 44, 39, 27, 17 and 15 kDa)
      by SDS-PAGE with the 44 kDa band containing two different proteins as shown by N
      terminal sequence analysis. On further chromatography of the 300 kDa complex on
      Arg-Sepharose the majority of the complex eluted from the affinity column as an
      undissociated complex. However, a small amount dissociated such that the Lys- and
      Arg-specific activities could be separated by eluting first with lysine then
      arginine, respectively. The 45 kDa protein of the complex was purified by further
      anion-exchange FPLC in the presence of octyl-beta-D-glucopyranoside and was shown
      to be an Arg-specific, thiol-activated, calcium-stabilized cysteine proteinase.
      The 48 kDa protein was also further purified in a similar fashion and shown to be
      a Lys-specific cysteine proteinase that was not inhibited by EDTA. The two 44 kDa
      and the 39, 27, 17 and 15 kDa proteins of the complex exhibit amino acid sequence
      homology and are proposed to be haemagglutinins/adhesins. The 45 kDa Arg-specific
      proteinase and one of the 44 kDa adhesins as well as the 15, 17 and 27 kDa
      adhesins are processed from the single polyprotein encoded by the gene designated
      prtR, with all proteins preceded by an Arg or Lys residue within the polyprotein.
      Similarly, the 48 kDa Lys-specific proteinase, the 39 and 15 kDa adhesins as well
      as the other 44 kDa adhesin of the 300 kDa complex are encoded by a single gene
      designated prtK, with all proteins preceded by an Arg or Lys residue within the
      polyprotein. The 39, 15 and 44 kDa adhesins of PrtK all exhibit high homology
      with the 44, 15, 17 and 27 kDa adhesins encoded by prtR, particularly the 15 kDa
      proteins which are identical. The cell-associated proteinase-adhesin complex,
      designated PrtR-PrtK, is therefore composed of the two gene products, the mature
      PrtR (160 kDa) and mature PrtK (163 kDa) that are further proteolytically
      processed (most likely autolytically) to release proteinase and adhesin domains
      that remain non-covalently associated. The fully processed PrtR-PrtK complex
      comprises the cysteine proteinases-PrtR45 and PrtK48 and seven sequence-related
      adhesin molecules, PrtR44, PrtR15, PrtR17, PrtR27 and PrtK39, PrtK15 and PrtK44.
      We propose that this proteinase-adhesin complex is a major virulence factor for
      P. gingivalis involved in the evasion of host defence and in the assimilation of
      haem and peptides.

PMID- 9245831
TI  - Iron acquisition from transferrin and lactoferrin by Pseudomonas aeruginosa
      pyoverdin.
AB  - Growth of Pseudomonas aeruginosa ATCC 15692 was promoted when the strain was
      cultured in an iron-depleted succinate medium, supplemented with transferrin at
      30%, 60% and 100% and lactoferrin at 60% and 100% iron-saturation. No significant
      differences between cell growth and pyoverdin production were observed when
      transferrin iron saturation was increased from 30% to 100%; however, cell growth
      and pyoverdin production were strongly dependent on lactoferrin iron saturation.
      Lower lactoferrin iron saturation (< 30%) resulted in more pyoverdin production
      and reduced cell growth. Incubation of pyoverdin (1.0 microM) with 10.0 microM
      transferrin (30%, 60% and 100% iron-saturated) or lactoferrin (60% and 100% iron
      saturated) led to quenching of pyoverdin fluorescence. Also, 24 h incubation of
      pyoverdin (20.0 microM) with these two proteins (20.0 microM, 30%, 60% and 100%
      iron-saturated transferrin and 60% and 100% iron-saturated lactoferrin) at 25
      degrees C resulted in increased absorbance at 460 nm. Both the fluorescence
      quenching and absorbance increases were iron-saturation-dependent. Taken
      together, these results support the conclusion that at physiological pH, P.
      aeruginosa pyoverdin can acquire from partially iron-saturated transferrin or
      lactoferrin.

PMID- 9245830
TI  - Localization of enzymically enhanced heavy metal accumulation by Citrobacter sp.
      and metal accumulation in vitro by liposomes containing entrapped enzyme.
AB  - A heavy-metal-accumulating Citrobacter sp. has been used for the treatment of
      metal-laden industrial wastes. Metal uptake is mediated via a cell-bound
      phosphatase that liberates inorganic phosphate which precipitates with heavy
      metals as cell-bound metal phosphate. A phosphatase-efficient mutant accumulated
      little UO(2)2+, while a phosphatase-overproducing mutant accumulated
      correspondingly more metal, with a uranium loading equivalent to the bacterial
      dry weight achieved after 6 h exposure of resting cells to uranyl ion in the
      presence of phosphatase substrate (glycerol 2-phosphate). The phosphatase,
      visualized by immunogold labelling in the parent and overproducing strains, but
      not seen in the deficient mutant, was held within the periplasmic space with, in
      some cells, a higher concentration at the polar regions. Enzyme was also
      associated with the outer membrane and found extracellularly. Accumulated uranyl
      phosphate was visible as cell-surface- and polar-localized deposits, identified
      by energy-dispersive X-ray analysis (EDAX), proton-induced X-ray emission
      analysis (PIXE) and X-ray diffraction analysis (XRD) as polycrystalline
      HUO2PO4.4H2O. Nucleation sites for initiation of biocrystallization were
      identified at the cytoplasmic and outer membranes, prompting consideration of an
      in vitro biocatalytic system for metal waste remediation. Phosphatidylcholine
      based liposomes with entrapped phosphatase released phosphate comparably to whole
      cells, as shown by 31P NMR spectroscopy in the presence of 'NMR-silent' 112Cd2+.
      Application of liposome-immobilized enzyme to the decontamination of uranyl
      solutions was, however, limited by rapid fouling of the biocatalyst by deposited
      uranyl phosphate. It is suggested that the architecture of the bacterial cell
      surface provides a means of access of uranyl ion to the inner and outer membranes
      and enzymically liberated phosphate in a way that minimizes fouling in whole
      cells.

PMID- 9245833
TI  - Differential induction of systemic resistance in Arabidopsis by biocontrol
      bacteria.
AB  - Selected nonpathogenic, root-colonizing bacteria are able to elicit induced
      systemic resistance (ISR) in plants. To elucidate the molecular mechanisms
      underlying this type of systemic resistance, an Arabidopsis-based model system
      was developed in which Pseudomonas syringae pv. tomato and Fusarium oxysporum f.
      sp. raphani were used as challenging pathogens. In Arabidopsis thaliana ecotypes
      Columbia and Landsberg erecta, colonization of the rhizosphere by P. fluorescens
      strain WCS417r induced systemic resistance against both pathogens. In contrast,
      ecotype RLD did not respond to WCS417r treatment, whereas all three ecotypes
      expressed systemic acquired resistance upon treatment with salicylic acid (SA).
      P. fluorescens strain WCS374r, previously shown to induce ISR in radish, did not
      elicit ISR in Arabidopsis. The opposite was found for P. putida strain WCS358r,
      which induced ISR in Arabidopsis but not in radish. These results demonstrate
      that rhizosphere pseudomonads are differentially active in eliciting ISR in
      related plant species. The outer membrane lipopolysaccharide (LPS) of WCS417r is
      the main ISR-inducing determinant in radish and carnation, and LPS-containing
      cell walls also elicit ISR in Arabidopsis. However, mutant WCS417rOA-, lacking
      the O-antigenic side chain of the LPS, induced levels of protection similar to
      those induced by wild-type WCS417r. This indicates that ISR-inducing bacteria
      produce more than a single factor that trigger ISR in Arabidopsis. Furthermore,
      WCS417r and WCS358r induced protection in both wild-type Arabidopsis and SA
      nonaccumulating NahG plants without activating pathogenesis-related gene
      expression. This suggests that elicitation of an SA-independent signaling pathway
      is a characteristic feature of ISR-inducing biocontrol bacteria.

PMID- 9245835
TI  - Two distinct uricase II (nodulin 35) genes are differentially expressed in
      soybean plants.
AB  - Nodule-specific uricase (uricase II) is a homotetramer of a 33-kDa polypeptide,
      nodulin 35, and plays a key role in the assimilation of nitrogen fixed by
      microsymbionts in most legumes that have determinate nodules. We have isolated
      two distinct genes, UR2 and UR9, that encode for nodulin 35 from a soybean
      genomic library. Their corresponding cDNAs were also isolated from a nodule cDNA
      library. UR2 and UR9 both encode for 309 amino acid proteins with 12 amino acid
      differences. The expression of these two genes in various organs of soybean was
      examined by reverse transcription-polymerase chain reaction with primers specific
      to each cDNA sequences. Expression of UR9 was almost specific in root nodules,
      although it was expressed in roots, primary leaves, and developing seed at very
      low levels. In contrast, the UR2 transcripts were present in almost all plant
      organs at low levels, but no enhancement of the expression was observed in
      nodules. Thus, UR9 behaves as a nodulin gene, whereas UR2 is a nonsymbiotic
      uricase II gene. The sequences of their potential promoter regions share high
      homology within regions up to about 400 bp upstream from the translation
      initiation sites. These results suggest that symbiotic and nonsymbiotic uricase
      II genes diverged by gene duplication and that relatively small alterations in
      the promoter sequence enable the nodule-specific expression.

PMID- 9245836
TI  - Nht1, a transposable element cloned from a dispensable chromosome in Nectria
      haematococca.
AB  - Certain isolates of the plant-pathogenic fungus Nectria haematococca mating
      population VI (MPVI) contain dispensable chromosomes that are unstable during
      sexual reproduction. Several of these chromosomes carry genes for phytoalexin
      detoxification and thus contribute to the pathogenic potential of this organism.
      A repeated DNA sequence, Nht1, was cloned from one of these dispensable
      chromosomes in N. haematococca MPVI. One copy of the repeated element (Nht1A) was
      completely sequenced. It is 2,198 bp long and it possesses incomplete inverted
      terminal repeats (ITRs) at each end. Nht1B, a partially sequenced copy of Nht1,
      has complete ITRs. Nht1A appears to contain 2 introns and encodes a protein of
      550 amino acids that is highly similar to the protein encoded by the Fusarium
      oxysporum transposon, Fot1. Due to the presence of ITRs, its repeated nature, and
      its similarity to Fot1, we conclude that Nht1 is a transposable element. Within
      North American N. Haematococca MPVI populations, Nht1 is distributed
      discontinuously. Its copy number in different field isolates varies from zero to
      approximately 100 copies per genome. The Nht1A source isolate is estimated to
      contain nine to 11 copies of Nht1; at least six are on the chromosome from which
      Nht1A was cloned.

PMID- 9245837
TI  - Mapping the elicitor and necrotic sites of Phytophthora elicitins with synthetic
      peptides and reporter genes controlled by tobacco defense gene promoters.
AB  - Elicitins are 10-kDa proteins secreted by Phytophthora and Pythium fungi that
      elicit a hypersensitive-like necrotic reaction, leading to resistance against
      fungal and bacterial plant pathogens. Induction of necrosis and resistance were
      previously shown to be borne by different sites of the molecule. Furthermore,
      sequence comparison indicated several potential residues necessary for necrosis.
      The role of one of these residues was previously evidenced with site-directed
      mutagenesis. In order to locate other necrosis-determining sites and reveal the
      defense-eliciting sites, we synthesized a series of synthetic peptides. Tests
      were performed on two types of transgenic tobacco plants, both transformed with a
      construction containing the beta-glucuronidase reporter gene, in one case
      controlled by the promoter of the multiple stimulus response gene str 246C and in
      the other by the promoter of the pathogenesis-related gene PR1a. We report that
      only certain peptides were found to be active. Whereas PR1a induction was
      consistently correlated with induction of necrosis, four peptides were observed
      to induce only str 246C expression without necrosis, which led to differentiate
      the defense-eliciting sites from the necrotic sites. From the structure-function
      relationship thus obtained, two different defense pathways were inferred to be
      independently induced by elicitins.

PMID- 9245838
TI  - Endopolygalacturonase genes from Colletotrichum lindemuthianum: cloning of CLPG2
      and comparison of its expression to that of CLPG1 during saprophytic and
      parasitic growth of the fungus.
AB  - Following the previous isolation of CLPG1, a gene encoding an
      endopolygalacturonase (endoPG) secreted into the culture filtrate of
      Colletotrichum lindemuthianum, we have isolated and sequenced an additional
      endoPG gene, CLPG2. This gene is present as a single copy in the genome of the
      fungus. At the amino acid level, CLPG2 shows 61% identity to CLPG1 and between 37
      to 59% identity to other fungal endoPGs. RNA blot analyses of endoPG gene
      expression were followed with specific probes during in vitro culture of the
      fungus. When conidia were used to inoculate a synthetic medium containing pectin
      as sole carbon source, only CLPG1 was found to be expressed after 3 days of
      culture. However, transferring the mycelium grown on glucose for 4 days to a
      pectin-containing medium allowed the detection of CLPG1 and CLPG2 transcripts as
      early as 12 h after transfer on this substrate. Expression of CLPG2 was transient
      while that of CLPG1 was more prolonged. Immunocytological localization of endoPG
      in C. lindemuthianum-infected bean tissues with antibodies against CLPG1
      confirmed that the protein is produced in planta and is associated with extensive
      degradation of the host cell wall. Detection of endoPG transcripts by reverse
      transcription-polymerase chain reaction revealed that CLPG1, but not CLPG2, is
      expressed at the beginning of the necrotrophic stage of infection. These results
      show that the two endoPG genes are differentially expressed and that CLPG1
      encodes the major secreted endoPG both during saprophytic growth and during plant
      infection.

PMID- 9245840
TI  - Mitochondrial DNA in aging and disease.

PMID- 9245841
TI  - The machinery of thought.

PMID- 9245842
TI  - Judicial attitudes to expert evidence in children's cases.

PMID- 9245843
TI  - Qualitative research methods in interventions in injury.

PMID- 9245844
TI  - Free-living energy expenditure and behaviour in late infancy.
AB  - OBJECTIVES: The energy requirements of infants are determined by body size,
      growth rate, and physical activity. Little is known of the determinants of energy
      expended on activity. The relation between free-living energy expenditure and
      behaviour was investigated in infants aged 9 and 12 months. METHODS: Total energy
      expenditure (TEE) was estimated by the doubly labelled water method and fat free
      mass was estimated from the 18O dilution space. Behaviour was assessed by two 24
      hour activity diaries. SUBJECTS: Thirty four normal healthy infants. RESULTS: TEE
      was negatively related to the time spent feeding and negatively related to the
      time spent upset. Body size, represented by fat free mass, accounted for only 19%
      of the variation in TEE, whereas the combination of fat free mass and two
      behavioural variables explained 46% of the variation in TEE. CONCLUSIONS:
      Behaviour contributed significantly to TEE. The energy requirements of individual
      subjects in this age group cannot be predicted with accuracy from body size
      alone.

PMID- 9245845
TI  - Treatment of hypogonadal adolescent boys with long acting subcutaneous
      testosterone pellets.
AB  - AIMS: Long acting subcutaneous testosterone pellets are of proved efficacy for
      the treatment of hypogonadal men, but have not been reported as a treatment
      modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone
      release have shown prolonged normalisation of testosterone levels for at least
      four months. Administration of a long acting, safe, effective, and convenient
      form of treatment is desirable when life-long treatment is indicated. PATIENTS
      AND METHODS: Eighteen boys (aged 13.9-17.5 years at the start of treatment)-seven
      with primary hypogonadism, nine with secondary hypogonadism, and two boys being
      treated with testosterone for tall stature--were given testosterone pellets (8-10
      mg/kg) every six months for 18 months. Height, weight, pubertal status, and
      psychosocial parameters were assessed and follicle stimulating hormone,
      luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1,
      3, 6, 12, and 18 months. Bone age was measured at 0 and 12 months. RESULTS: In
      all boys growth velocity continued appropriately for bone age. Puberty continued
      to progress in all boys and in two boys the amount of virilisation exceeded that
      seen with previous treatment with intramuscular testosterone. After testosterone
      administration, follicle stimulating hormone and luteinising hormone suppressed
      incompletely in the boys with primary hypogonadism. Serum testosterone ranged
      from 4.3 to 26.7 nmol/l at three months to less than 10 nmol/l at six months
      after implantation. Prolactin and lipid levels were normal throughout the study.
      By report, there was an improvement in mood and emotional wellbeing. No pellet
      extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS: All boys
      preferred this mode of testosterone administration to intramuscular injections.
      Long acting subcutaneous testosterone pellets are safe, efficacious, well
      tolerated, and convenient, and result in normal physical growth and improved
      psychological outlook in adolescent hypogonadal boys.

PMID- 9245846
TI  - Randomised controlled trial assessing the effectiveness of a booklet on the
      duration of breast feeding.
AB  - OBJECTIVE: To test the efficacy of an information booklet to increase the
      duration of breast feeding. RESEARCH DESIGN: Randomised design, stratifying by
      maternal residence and working activity. Two hundred women were recruited, 103
      received the booklet and verbal counselling and 97 verbal counselling only.
      POPULATION: Infants observed from 15 September 1993 to 15 June 1994 in the well
      baby outpatient clinic of the Paediatric Institute of the Catholic University of
      Rome, Italy. MAIN RESULTS: No statistically significant difference was found
      between the two groups in the prevalence of exclusive or complementary breast
      feeding at 6 months of age: 48.5% and 59.2% in the intervention group, 43.7% and
      51.5% in the control group. The median duration of exclusive or complementary
      breast feeding was 24 and 27 weeks in the treated group, 22 and 25 in the control
      group. CONCLUSIONS: The information booklet alone does not seem to increase the
      duration and the prevalence of breast feeding at 6 months of age. The use of
      written material with a more individualised support and more extensive use of
      randomised clinical trials in the evaluation of health promoting programmes is
      recommended.

PMID- 9245847
TI  - Adult height in patients with childhood onset atopic dermatitis.
AB  - Cross sectional studies have reported impaired growth in children with atopic
      dermatitis. If this growth impairment is irreversible, it would be expected to
      adversely influence final height attainment. The standing heights and other
      anthropometric parameters were assessed in 35 adults with onset of atopic
      dermatitis before 5 years of age and a control group of 35 adults with adult
      onset contact dermatitis or psoriasis. There was no significant difference in the
      standing height SD score, mid-parental height SD score, sitting height SD score,
      subischial leg length SD score, nor body mass index between the atopic dermatitis
      and control groups. The standing height SD score was not significantly different
      among: (a) patients with atopic dermatitis affecting less than 50% of their body
      surface area and those with greater than 50% affected; (b) patients using the
      four different potency topical corticosteroids; and (c) patients with atopic
      dermatitis without asthma and those with coexisting asthma. It is concluded that
      short stature is not a feature of our group of adult patients with onset of
      atopic dermatitis before 5 years of age, continuing into adulthood, and severe
      enough to require specialist care. This suggests that if growth impairment occurs
      in childhood, it is likely to be temporary and reversible.

PMID- 9245849
TI  - Aminopenicillin allergy.
AB  - Eight two children with histories of maculopapular or urticarial rashes during
      aminopenicillin treatment underwent skin tests, patch tests, radioallergosorbent
      assays and, in some cases, oral challenges. Hypersensitivity was diagnosed in
      eight (9.8%): immediate in four with urticarial reactions and delayed (that is
      cell mediated) in four with maculopapular rashes. In 49 children (38 with
      maculopapular eruptions, 11 with urticarial/angiooedematous reactions), negative
      allergologic findings were confirmed using oral challenges with the suspected
      drug. Maculopapular rashes may reflect delayed hypersensitivity to
      aminopenicillins, which can be diagnosed on the basis of late intradermal
      reactions and/or patch test positivity. The allergen panel must include the
      suspected aminopenicillin itself, as many cases are side chain specific. Most
      patients with urticarial reactions (more typical of immediate hypersensitivity)
      will also react to penicilloyl polylysine and minor determinant mixture. The time
      elapsed between the reaction and testing must be considered if negative results
      emerge, because IgE mediated sensitivity (unlike cell mediated forms) declines in
      the absence of antigen exposure.

PMID- 9245848
TI  - Nutritional support and growth in thalassaemia major.
AB  - Twelve thalassaemic children under 3 years of age received intensive nutritional
      support for one month and were discharged on a prescribed diet of locally
      available foods. Anthropometry, bioelectrical impedance analysis and dietary
      intake were longitudinally assessed. Mean energy intake was 20% greater than the
      recommended daily allowance during nutritional supplementation as compared with
      below the recommended daily allowance before and after the period of nutritional
      support. Weight, but not height, significantly increased during the support
      period and was due to increases in both fat free mass and fat mass. Body weight,
      fat free mass and fat mass declined in line with the reduced intake upon return
      home; however, height velocity accelerated and exceeded normal through the fourth
      month before resuming a below normal rate. It can be concluded that (1)
      nutritional stunting as the result of reduced nutrient intake is an important
      cause of growth failure in young children with thalassaemia and is responsive to
      nutritional support, (2) the deficit in height velocity was due to retarded
      truncal height growth, and (3) the bioelectrical impedance analysis method is
      suitable for body composition analysis of thalassaemic children.

PMID- 9245851
TI  - Mechanisms of ischaemic stroke after chickenpox.
AB  - Ischaemic stroke is a recognized complication of chickenpox. Seven cases of
      ischaemic stroke in children after recent varicella infection are discussed in
      detail to emphasise that there are several mechanisms by which this may arise.

PMID- 9245850
TI  - Heterogeneity of atypical haemolytic uraemic syndromes.
AB  - Atypical, non-diarrhoea associated haemolytic uraemic syndrome (D-HUS) is a
      heterogeneous disorder with a generally poor outcome, although this view has now
      been questioned. The clinical and laboratory features of 23 children with D-HUS,
      representing a third of all patients with HUS seen during the last 26 years, were
      examined. The median age was 4.9 years (range 3 days-13.8 years). Twenty one
      children (91%) survived the initial phase. All patients except six infants aged <
      18 months required dialysis (74%). Hypertension (43%), cardiomyopathy (43%), and
      cerebral convulsions (48%) were common. Nineteen (83%) children were followed up
      for a median period of 5.5 years (range 0.5-23.4). Only five (26%) patients,
      among them four infants, recovered completely. Six (32%) patients had one to 10
      recurrences, including two siblings with neonatal onset, and eight (42%)
      developed end stage renal failure. Five children underwent cadaveric renal
      transplantation, with recurrence and subsequent graft failure in two. Four
      children died, resulting in an overall mortality of 26%. Atypical HUS is
      heterogeneous with regard to epidemiology, pathophysiology, and outcome. Children
      with a recurrent, familial, or neonatal course have worse outcomes; in contrast,
      infants not requiring dialysis in the acute phase have a better prognosis.

PMID- 9245852
TI  - Campylobacter 0:41 isolation in Guillain-Barre syndrome.
AB  - Over a period of 15 months, 17 children were admitted to the Red Cross War
      Memorial Children's Hospital (RCWMCH) in Cape Town with Guillain-Barre syndrome.
      Stool specimens were collected from 14 children and campylobacter was isolated
      from nine. Six of the nine isolates of Campylobacter jejuni were further
      identified as C jejuni biotype 2, serotype 0:41. This biotype 2, serotype 0:41
      has been identified in only 12 of the 7119 campylobacter isolates at the RCWMCH
      over a 19 year period. Eight of the nine patients with campylobacter isolates and
      one of five with negative stool cultures required ventilation. Patients with C
      jejuni biotype 2, serotype 0:41 were ventilated for a mean (SD) of 33.5 (19.4)
      days, whereas patients with other campylobacter isolates were ventilated for 17.3
      (3.8) days. This is the first report of campylobacters of serotype 0:41 in
      Guillain-Barre syndrome and could reflect a geographical isolation of this
      strain.

PMID- 9245853
TI  - Phenotypic diversity in siblings with partial androgen insensitivity syndrome.
AB  - The androgen insensitivity syndrome is a heterogeneous disorder with a wide
      spectrum of phenotypic abnormalities, ranging from complete female to ambiguous
      forms that more closely resemble males. The primary abnormality is a defective
      androgen receptor protein due to a mutation of the androgen receptor gene. This
      prevents normal androgen action and thus leads to impaired virilisation. A point
      mutation of the androgen receptor gene affecting two siblings with partial
      androgen insensitivity syndrome is described. One had cliteromegaly and labial
      fusion and was raised as a girl, whereas the other sibling had micropenis and
      penoscrotal hypospadias and was raised as a boy. Both were shown to have the
      arginine 840 to cysteine mutation. The phenotypic variation in this family is
      thus dependent on factors other than abnormalities of the androgen receptor gene
      alone.

PMID- 9245854
TI  - Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal
      dystrophy syndrome successfully treated with immunosuppression.
AB  - A 15 year old boy with autoimmune polyendocrinopathy-candidosis-ectodermal
      dystrophy syndrome suffered recurrent episodes of severe intractable diarrhoea,
      steatorrhoea, and hypocalcaemia. The only treatment modality, which controlled
      the malabsorption syndrome, was immunosuppression with intravenous high dose
      methylprednisolone and oral methotrexate maintenance therapy.

PMID- 9245855
TI  - Assessment of bone status using the contact ultrasound bone analyser.
AB  - Broadband ultrasound attenuation (BUA) was measured at the calcaneum in 367
      healthy white schoolchildren (193 girls and 174 boys) aged 6-15 years. The mean
      calcaneal BUA increased with age and was significantly related to age, height,
      and weight. Measurement of calcaneal BUA may be helpful in the radiation free
      assessment of childhood disorders associated with increased fracture risk.

PMID- 9245856
TI  - Effect of growth hormone on fatty liver in panhypopituitarism.
AB  - A 17 year old boy was admitted because of short stature and hepatomegaly. He was
      diagnosed with panhypopituitarism and fatty liver. The fatty liver improved, not
      with hydrocortisone or levothyroxine treatment, but with growth hormone
      administration. The fatty liver in this patient was attributable to a growth
      hormone deficient state.

PMID- 9245857
TI  - Dental attitudes, knowledge, and health practices of parents of children with
      congenital heart disease.
AB  - A total of 60 children with severe congenital cardiac disease from the Great
      Ormond Street Hospital for Children and Guy's Hospital children's department were
      matched for age, gender, social class, and ethnic origin with 60 healthy children
      from the trauma clinic of the Department of Orthodontics and Paediatric Dentistry
      at Guy's Dental Hospital, London. The parents' attitude, knowledge, and dental
      health practices were assessed by questionnaire. The cardiac group had
      significantly poorer dental health practices than the healthy group. Of the
      cardiac children 18% had never visited the dentist compared with only 3% for the
      healthy group. It is difficult to assess the importance of this in terms of a
      serious health hazard. Current practice of cardiac physicians is to recommend
      that children with heart disease seek out and attend a dentist, the advice
      usually being accompanied by the presentation of a 'heart card' detailing
      antibiotic prophylaxis regimens if extractions are required. The data presented
      here shows that this strategy has failed.

PMID- 9245858
TI  - Management of childhood arthritis. Part 2: Chronic arthritis.

PMID- 9245859
TI  - How to organise the paediatric MRCP (UK) part II clinical examination.

PMID- 9245860
TI  - Iron deficiency anaemia in infancy and early childhood.

PMID- 9245861
TI  - Early recognition of metabolic decompensation.

PMID- 9245862
TI  - Mucosal prelaminated flaps for physiological reconstruction of intraoral defects
      after tumour resection.
AB  - In order to provide vascularised mucosa for reconstruction of intraoral defects
      after radical tumour resection, 5 distal radial forearm flaps and 1 fibula flap
      were prelaminated. Prelamination was performed by fixing small, full thickness
      mucosa pieces onto the fascia and covering the mucosa with an alloplastic sheet
      as large as the future flap. The alloplastic material was a silicone sheet (n =
      2), a Gore-tex sheet (n = 3) or a titanium sheet (n = 1). The mucosa and the
      alloplastic material were covered by the skin and subcutaneous tissue which had
      been elevated to expose the fascia. With the silicone and titanium sheets, the
      mucosa spread on the fascia and the final flaps were thin, pliable, mucus
      producing and larger than the original mucosa pieces. With the Gore-tex sheets,
      extension of the mucosa was prevented by adhesions and the area of mucosa on the
      final flap was the same size as the original graft. The six prelaminated flaps
      were harvested after 8-10 weeks. During this time the patients had radiotherapy
      and chemotherapy. Preserving the skin and subcutaneous tissue reduced donor site
      morbidity. Six patients had intraoral defects successfully reconstructed with
      mucus-producing prelaminated flaps.

PMID- 9245863
TI  - Laser scanning for the identification of repeatable landmarks of the ears and
      face.
AB  - OBJECTIVE: To determine whether or not landmarks of the ears and face could be
      reliably identified using a laser scaning system. DESIGN: A single centre study
      with two assessors jointly agreeing the siting of the landmarks on the ear on two
      separate occasions from an original laser scanned image. SETTING: University
      based research study in London, UK. SUBJECTS: 20 subjects, 11 males, 9 females,
      aged 16-24 years with normal facial development. MAIN OUTCOME MEASURES:
      Differences were determined between the locations of landmarks on the two
      occasions studied. Differences were assessed for the x, y and z co-ordinates of
      each point. RESULTS: The mean difference between the two sitings of 21 landmarks
      ranged between 0 and 0.85 mm in the x, y and z axes. With a small number of
      exceptions, the differences were not statistically significant. The three
      dimensional mean differences between the two sitings of each landmark ranged
      between 1 and 2.5 mm. Coefficients of repeatability ranged between 1.6 and 7.0
      mm. CONCLUSIONS: Landmarks of the ears and face from a laser scanned image can be
      sited consistently by two assessors. Since the landmarks can be located it should
      be possible to evaluate dimensional measurements of the ear and its position on
      the face.

PMID- 9245864
TI  - The fate of the oblique abdominal muscles after free TRAM flap surgery.
AB  - During recent years, clinical research on the donor site morbidity after free or
      pedicled transverse rectus abdominis myocutaneous (TRAM) flap surgery has been
      focusing on the reduced flexion capacity of the abdominal wall. However, the
      rectus abdominis muscles have close interactions with their synergists and
      antagonists and collaborate with their neighbouring muscles. The purpose of this
      study was to examine the consequences of partially resecting the rectus abdominis
      muscle on the different muscle groups of the abdominal wall. Twenty free TRAM
      flap patients, 12-61 months (mean 32.1 months) after surgery, were clinically
      examined, evaluated for curl-up performance and underwent isokinetic dynamometry
      for flexion, extension and rotation. The patients were compared with 20 non
      operated controls. Nineteen patients answered a questionnaire. Abdominal wall
      abnormalities occurred in 10 patients: umbilical asymmetry (n = 3), abdominal
      wall asymmetry (n = 4), lower abdominal bulging (n = 2) and hernia (n = 1). Curl
      up performance was less in the TRAM flap patients (P = 0.001, Mann-Whitney).
      Isokinetic flexion, extension and rotation were also less in the TRAM flap
      patients (Fisher's exact test). This study indicates that what has been believed
      to be 'limited' surgical damage to the abdominal wall leads to an important
      reduction in flexion strength but to an even more important reduction of rotation
      strength due to bilateral displacement and damage of the insertion of the oblique
      muscles. Partial compensation by synergists is variable and unpredictable on an
      individual basis. These functional disorders can potentially lead to important
      changes in activities of daily life.

PMID- 9245865
TI  - The donor site morbidity of free DIEP flaps and free TRAM flaps for breast
      reconstruction.
AB  - This study was undertaken to demonstrate that the deep inferior epigastric
      perforator (DIEP) flap can provide the well-known advantages of autologous breast
      reconstruction with lower abdominal tissue while avoiding the abdominal wall
      complications of the transverse rectus abdominis myocutaneous (TRAM) flap.
      Eighteen unilateral free DIEP flap breast reconstruction patients were assessed
      12-30 months (mean 17.8 months) after surgery. Clinical examination, physical
      exercises and isokinetic dynamometry were performed preoperatively and two months
      and one year postoperatively. Intraoperative segmental nerve stimulation, visual
      evaluation and postoperative CT scans were also used to quantify the damage to
      the rectus muscle. The 18 patients were then compared with 20 free TRAM flap
      patients and 20 non-operated controls. Two DIEP flap patients presented with
      abdominal asymmetry. A limited decrease of trunk flexing strength was noticed but
      rotatory function was intact. Ten of the TRAM flap patients had umbilical or
      abdominal asymmetry, bulging or hernias. TRAM flap patients showed a
      statistically significant reduction in strength to flex and to rotate the upper
      trunk compared to both the one year postoperative DIEP flap group and the control
      group. The answers to a questionnaire revealed impairment of activities of daily
      living for some TRAM flap patients while the activities of all DIEP flap patients
      were unaffected. Our data demonstrate that the free DIEP flap can limit the
      surgical damage to the rectus abdominis and oblique muscles to an absolute
      minimum. We believe it is worthwhile to spend extra operative time, the main
      disadvantage of this technique, to limit late postoperative weakness of the lower
      abdominal wall.

PMID- 9245866
TI  - Nipple-areola reconstruction by tattooing and nipple sharing.
AB  - In a reconstructed breast the nipple-areola complex can be restored by various
      techniques, most of which are complicated and may leave residual scarring at the
      donor site. The primary intradermal tattooing and nipple sharing technique for
      nipple-areola reconstruction is simple and can be done under local anaesthesia.
      We present our experience of 31 patients who had 32 areolar reconstructions using
      intradermal tattooing (one patient had bilateral breast reconstruction).
      Seventeen patients had a nipple reconstruction by the nipple sharing technique.
      At follow-up of 2 months to 4 years, 4 patients have required further tattooing
      because of fading of the pigment and 1 patient has a gross areolar colour
      mismatch. There have been no nipple graft failures and the reconstructed nipples
      have adequate projection.

PMID- 9245867
TI  - Free tissue transfer for leg reconstruction in children.
AB  - Twenty-five free tissue transfers for reconstruction after lower limb trauma or
      release of scar contractures were performed in 23 children over an 8-year period.
      The ages ranged from 2 to 14 years (mean 7.1 years). Fourteen (61%) patients had
      major associated injuries. The reconstruction sites were all in the distal leg.
      The overall vascular success rate was 96%. Three patients underwent re
      explorations because of vascular insufficiency. One flap failed and two were
      salvaged. The causes of vascular complications were considered to be inadequate
      debridement of an avulsed vessel, venous kinking and inadequate protection of the
      vascular pedicle. The three cases with vascular insufficiency were children with
      associated injuries on the ipsilateral leg proximally. Postoperative
      complications were not uncommon (28%). Six of the seven complications occurred in
      patients with major associated injuries. The mean follow-up was 57 months. Long
      term problems such as a limping gait, frequent flap ulcers, toe contracture or a
      bulky flap were common. Our results suggest that free tissue transfer is reliable
      and safe for the reconstruction of major leg injuries in children. Associated
      injuries proximal to the reconstructed defects on the ipsilateral leg predispose
      to more vascular complications. Since postoperative complications and long-term
      morbidity are common in children, special precautions should be taken with the
      preoperative assessment, planning, execution of surgery and postoperative care to
      achieve better results.

PMID- 9245868
TI  - Mild hypothermia protects against ischaemia-reperfusion injury in rabbit skeletal
      muscle.
AB  - In three groups of rabbits, the rectus femoris muscle was subjected to 4 hours of
      total ischaemia. In Group 1 (normothermia, n = 5) the core temperature was
      maintained within the range 36-38 degrees C for the duration of ischaemia. In
      Group 2 (total hypothermia, n = 5) the core temperature was allowed to fall to
      31.5-33.5 degrees C. In Group 3 (muscle only hypothermia, n = 5) core temperature
      was maintained as in Group 1 but the muscle temperature was allowed to fall to
      29.5-31.5 degrees C. After 24 hours of reperfusion the muscles were harvested and
      measurements made of muscle viability, oedema and myeloperoxidase content. The
      mean (s.e.m.) muscle viability of Group 1, 19.5 (3.8)%, was significantly less
      than that of both Group 2, 86.0 (2.0)%, and Group 3, 87 (4.1)%, (P < 0.001).
      Muscle oedema and myeloperoxidase levels were elevated in all experimental
      groups, but differences were not significant. These findings indicate that
      ischaemia-reperfusion injury in skeletal muscle in this model is highly
      temperature-sensitive, small reductions in muscle temperature during ischaemia
      providing significant protection against ischaemia-reperfusion injury.

PMID- 9245869
TI  - Follow-up requirements for thick cutaneous melanoma.
AB  - The primary aim of postoperative melanoma follow-up is the early detection and
      treatment of treatable recurrences which gives a survival advantage to these
      patients. The need for follow-up is universally accepted. However, there is
      ongoing controversy about the duration of follow-up and frequency of reviews. We
      present a retrospective review of 244 patients with localised thick (> or = 4.0
      mm) cutaneous melanoma, who had completed a 10-year follow-up or had died form
      their melanoma within 10 years. For these criteria, this is the largest series of
      this type which has been reported to date. The incidence of treatable recurrences
      peaked in the first postoperative year at 40% and then rapidly decreased,
      levelling off after year 5 at 2.5% per annum. We believe that this high incidence
      of treatable recurrences reinforces the need for 10-year follow-up of these
      patients. We also recommend that the annual frequency of follow-up reviews in
      each year be based on that year's risk for getting a treatable recurrence.
      Following this principle, we provide an example of such a follow-up programme.

PMID- 9245870
TI  - Plasma concentrations of tumour necrosis factor-alpha and interleukin-6 during
      burn wound surgery or dressing.
AB  - BACKGROUND: Clinical deterioration after burn wound manipulation may be related
      to the release of cytokines including tumour necrosis factor-alpha (TNF) and
      interleukin-6 (IL-6). METHODS: The two cytokines were assayed by immunoenzymetric
      assay in blood samples taken before and during manipulation of the burn wound. An
      antibiotic, teicoplanin, was administered to half the patients at the start of
      the procedure in a randomized fashion as part of a separate trial. FINDINGS:
      Sixty patients with a median burn size of 8% (range 1-56%) were studied during
      dressing change (n = 40) or burn excision (n = 20). There was little change in
      TNF levels between preoperative and recovery samples but IL-6 concentrations
      increased three-fold, particularly in those with large recent burns or
      bacteraemia, and were correlated with poor clinical outcome. The presence of
      teicoplanin did not significantly affect the levels of either cytokine.
      INTERPRETATION: The systemic cytokine response to burn wound dressing or
      debridement is predominantly that of IL-6 and it is not significantly reduced by
      preventing Gram-positive bacteraemia during the procedure.

PMID- 9245871
TI  - Hyaluronic acid induces tumour necrosis factor-alpha production by human
      macrophages in vitro.
AB  - Foetal wounds heal with minimal or no scar formation. High levels of hyaluronic
      acid (HA) have been implicated as a contributory factor. Macrophages are
      essential for normal wound healing, a role facilitated by secretion of an array
      of cytokines. Of these, tumour necrosis factor alpha (TNF-alpha) has been shown
      to reduce wound collagen levels and thus scarring. This study examines the
      ability of HA to stimulate TNF-alpha production by human macrophages. The human
      U937 myelomonocytic cell line was differentiated into DU937 adherent macrophages.
      DU937 monolayers were exposed to HA at concentrations of 0.1, 1, 10 and 100
      micrograms/ml. Conditioned media from HA-exposed monolayers were assayed for TNF
      alpha activity using a standard L929 fibroblast bioassay. TNF-alpha activities of
      HA-exposed DU937 culture supernatants were compared to those of controls and
      expressed as % cytotoxicity. Exposure of macrophages to HA at concentrations of
      10 micrograms/ml and 100 micrograms/ml significantly stimulated TNF-alpha
      production, as demonstrated by % cytotoxicities expressed as median
      (interquartile range) of 33.5 (29-34.5)% (P = 0.03) and 77.5 (67-85)% (P = 0.029)
      respectively (Mann-Whitney U test). This effect was specifically associated with
      TNF-alpha generated during HA exposure, as these cytotoxic effects could be
      abolished by addition of anti-TNF-alpha antibody, reducing cytotoxicity to 9 (6.5
      13.5)% and 8.5 (6-12)% respectively. These observations indicate that HA
      stimulates TNF-alpha production by human macrophages. TNF-alpha is known to
      downregulate fibroblastic collagen synthesis within experimental wounds. We
      suggest that the high levels of HA within foetal wounds may play a part in
      limiting fibroplasia, and thereby limit scarring, via an upregulation of TNF
      alpha production from wound macrophages.

PMID- 9245872
TI  - A molecular approach to bone regeneration.
AB  - Bone morphogenetic proteins (BMPs) are becoming increasingly recognised as
      valuable molecular tools for regenerating bone and accelerating fracture healing.
      New bone growth is the result of BMP-induced differentiation of pluripotent
      mesenchymal cells along osteoblastic pathways. This phenomenon recapitulates in
      adults specific aspects of skeletal morphogenesis co-ordinated by BMPs during
      development. An understanding of the basic scientific research which has led to
      the characterisation and purification of these remarkable molecules is essential
      if their full therapeutic potential is to be realised.

PMID- 9245873
TI  - Ischial pressure sore coverage: a rationale for flap selection.
AB  - The role of wound debridement and flap coverage in treating pressure sores is
      clearly established. However, criteria and supportive clinical data for specific
      flap selection and the sequence of flaps for coverage of the ischium remain ill
      defined. From 1979-1995, 114 consecutive patients underwent flap coverage of 139
      ischial pressure sores. Preoperative risk factors, prior flap history, defect
      size, flap success, complication rates, and the length of hospitalization were
      retrospectively evaluated and compared for 112 flaps in 87 patients. Flap success
      was defined as a completely healed wound. Average follow-up was 10 months (range:
      1 month-9 years). Overall, 83% (93/112) of the flaps healed. In the majority of
      cases (75%, 84/112), wound debridement and flap reconstruction was achieved in a
      single stage. However, there were significant differences in the healing rates
      among the various flaps used. The inferior gluteus maximus island flap and the
      inferior gluteal thigh flap had the highest success rates, 94% (32/34) and 93%
      (25/27), respectively, while the V-Y hamstring flap and the tensor fascia lata
      flap had the poorest healing rates, 58% (7/12) and 50% (6/12), respectively. Flap
      success was not significantly affected by the age of the patient or the prior
      number of flaps used and preoperative risk factors were equally distributed
      across all types of flaps. The overall complication rate was 37% (41/112), most
      commonly from a slight wound edge dehiscence (n = 16) that healed with local
      wound care within one month postoperatively. Results of this study show that
      proper flap selection and the appropriate sequence of flap use significantly
      improve success rates for ischial pressure sore coverage in both the short- and
      long-term. Based upon flap reliability (successful healing rates), reusability,
      and the need to preserve as many future flap options as possible, a rationale for
      flap selection is presented which can be individualized to any patient.

PMID- 9245875
TI  - Carcinoma in a pressure sore.

PMID- 9245874
TI  - Growth inhibition of cultured fibroblasts by extracts from human dermis.

PMID- 9245876
TI  - Boron neutron capture therapy.

PMID- 9245877
TI  - Positron emission tomography (PET) scanning in breast cancer.

PMID- 9245878
TI  - Risk assessment of the nuclear medicine patient.
AB  - Two types of risk are identified following the administration of a
      radiopharmaceutical to a patient: the risk to the patient, and the risk to
      critical groups exposed to the patient. The method for quantifying the risk to
      the patient is described in terms of estimating the effective dose. The main
      limitations in these estimates for adult and paediatric patients are
      uncertainties in the biokinetic data, and the assumption of a uniform
      distribution of activity in each organ. Effective doses from most nuclear
      medicine procedures will not exceed twice the annual dose from natural background
      radiation in the UK. Lack of human placental transfer data is now the main
      limitation to estimating fetal doses. The characteristics of two methods which
      can be used to derive the dose to critical groups exposed to nuclear medicine
      patients are reviewed. It is shown that studies using either method have
      indicated that the current recommendations in the UK for restricting the exposure
      of these groups and the recommendation recently proposed for restricting the
      exposure of pregnant members of staff are not appropriate. Revised
      recommendations for restricting the behaviour of patients administered iodine-131
      should await the results of a current multicentre trial. The method to estimate
      the dose to a breast-fed infant from a mother administered a radiopharmaceutical
      is outlined, and the recently revised guidance for interrupting breast feeding is
      summarised. When a recommendation for controlling risk is to be derived from
      dosimetry data obtained from a number of individuals, an outstanding issue to be
      resolved is the value (e.g. 95% upper confidence limit) on which it should be
      based.

PMID- 9245879
TI  - In vivo demonstration of microcalcification in breast cancer using high
      resolution ultrasound.
AB  - 84 patients with 89 primary breast cancers underwent high resolution ultrasound,
      mammography and histological evaluation. Pathological specimens and hard copy
      images of both imaging modalities were reviewed in order to document the amount
      of microcalcification present in each tumour. A total of 44, 40 and 46 tumours
      had visible microcalcification using high resolution ultrasound, mammography and
      histology, respectively. Using mammography as the gold standard, ultrasound
      achieved a sensitivity of 95%, specificity of 87.8% and accuracy of 91% in the
      detection of microcalcification. Histology had a sensitivity of 80%, specificity
      of 71.4% and accuracy of 75.3%. We conclude that ultrasound is sensitive in the
      detection of microcalcification in breast cancer when they are within a mass
      lesion, and is a reliable diagnostic sign of carcinoma when present.

PMID- 9245880
TI  - The combined use of ultrasound and densitometry in the prediction of vertebral
      fracture.
AB  - Measurement of ultrasonographic parameters provides information concerning not
      only bone density but also bone architecture. We investigated the usefulness of
      ultrasonographic parameters and bone mineral density for evaluating the
      probability of vertebral fracture. 397 postmenopausal women (59.1 +/- 6.0 years)
      with (n = 178) or without (n = 219) atraumatic vertebral fractures were studied.
      In all women, bone mineral density (BMD) of the lumbar spine was evaluated by
      dual X-ray absorptiometry (DXA) and speed of sound (SOS); broadband ultrasound
      attenuation (BUA) and Stiffness in the calcaneus were evaluated by an Achilles
      unit (Lunar Corporation). Ultrasonographic parameters and BMD were compared by
      examining the magnitude of the odds ratios, to determine which produces the
      highest estimate of the probability of odds of fracture, and by examining widths
      of the respective confidence intervals (CI) to show which estimate of odd ratio
      is the most precise. The relative risk of vertebral fracture, after adjusting for
      potential confounders, was 3.5 (CI 2.6-4.8) for BUA; 4.5 (CI 3.2-6.2) for SOS;
      5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound (US)
      parameters were still significant independent predictors of vertebral fracture,
      even after adjusting for BMD. The relative risk of fracture for a simultaneous
      decrease by 1 SD of BMD and by 1 SD of each ultrasound parameter was 17.3 (CI 9.4
      39.6) for BMD and SOS; 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7)
      for BMD and Stiffness. Our data suggest that US and BMD provide complementary
      information which can be combined to improve estimates of vertebral fracture
      risk.

PMID- 9245881
TI  - Relationship between histological type and endosonographic detection of regional
      lymph node metastases in gastric cancer.
AB  - The aim of the study was to compare the ability of endoscopic ultrasonography
      (EUS) in detecting lymph node metastases in differentiated and undifferentiated
      gastric adenocarcinoma. EUS was performed in 149 patients with differentiated or
      undifferentiated gastric cancer. Histopathological findings were compared with
      pre-operative EUS findings in a total of 2961 resected lymph nodes. The EUS
      detection rates of metastasis to individual nodes in relation to node size, the
      ratio of the metastasized area to the cross-sectional area of the node and to the
      depth of primary tumour invasion, were also investigated. The accuracy and
      negative predictive values of EUS for detecting metastatic lymphadenopathy in
      each patient were significantly higher for differentiated (87%, 94%) than for
      undifferentiated (71%, 71%) tumours. The detection rate of individual node
      metastasis was higher for differentiated (31%) than for undifferentiated (21%)
      tumours. For differentiated lesions, EUS detected more small nodal metastases (<
      5 mm in diameter) (p < 0.01) and more nodes involved with a relatively small
      proportion of the metastasized area to the cross-sectional area of the node (<
      1/3 involvement) (p < 0.05). In relatively superficial lesions, such as pT1 and
      pT2, the pre-operative EUS detection rate of metastatic nodes was higher for
      differentiated than for undifferentiated tumours. In conclusion, the ability of
      EUS to detect nodal metastases is related to the histological type of gastric
      cancer.

PMID- 9245882
TI  - Pre-operative TN staging of gastric cancer using a 15 MHz ultrasound miniprobe.
AB  - The aim of the study was to evaluate the usefulness of and problems associated
      with a new endoscopically guided ultrasound miniprobe, used for pre-operative
      staging of gastric cancers. 59 cases of gastric cancer were prospectively
      examined with a 15 MHz ultrasound miniprobe. The results of the ultrasound
      imaging were compared with the histological findings of the resected specimens.
      The accuracy of the miniprobe for depth of invasion (T category) was 61% for all
      tumours, and 72% and 40%, respectively, for T1 and T2 to T4 lesions. If
      indeterminate cases due to ultrasound attenuation were excluded, the accuracy was
      improved to 82% for T1 and 57% for T2 to T4 tumours, respectively. The accuracy
      of the miniprobe for nodal staging (N category) was 69% overall, and 86%, 25% and
      14% for stages N0, N1 and N2, respectively. In tumours classified on the basis of
      endoscopic types, the miniprobe staged early type gastric cancers (T category =
      73%, N category = 80%) significantly (p < 0.01) more accurately than advanced
      ones (T category = 21%, N category = 36%). This study suggests that the miniprobe
      is indicated for pre-operative TN staging when endoscopy reveals an early gastric
      cancer.

PMID- 9245883
TI  - Computing patient doses of X-ray examinations using a patient size- and sex
      adjustable phantom.
AB  - Both the use of traditional fluoroscopy and the increasing use of modern digital
      techniques in radiology and interventional radiology demand the development of
      versatile computer programs for patient dose determinations. Long computing times
      restrict the use of Monte Carlo (MC) methods in dose monitoring applications
      where the radiological views change frequently. In the Organ Doses Calculation
      Software application (ODS-60), the phantom model is similar in principle to the
      Alderson-Rando (A-R) phantom, but its sex, size and shape is modified according
      to a particular patient. Organ and effective doses are computed online (in a few
      seconds) using a method similar to the traditional dose planning systems used in
      radiotherapy. In this paper, the new ODS-60 software is presented in detail and
      its capabilities are demonstrated. Software performance was determined by
      comparing the results with those from independent methods. In the case of a
      reference man-sized male, the effective dose was about 7% larger than the
      effective dose given in another publication. In the case of a reference woman
      sized female, the disagreement with the other method was greater (33%).
      Anatomical differences between the phantom models (ODS-60 and MC) were found to
      be the main reasons for these findings. This paper shows the advantage of using a
      patient size- and sex-adaptable phantom for patient dose determinations; the
      conversion coefficient from entrance surface dose-to-effective dose ratio between
      male (170 cm, 85 kg) and a female (160 cm, 43 kg) varies in the range 1.5-2.

PMID- 9245884
TI  - Radiation dose and in vitro precision in paediatric bone mineral density
      measurement using dual X-ray absorptiometry.
AB  - Dual X-ray absorptiometry (DXA) is one of the most widely used techniques for non
      invasive assessment of bone integrity. There is a growing demand for measurement
      of paediatric bone status. In DXA the principal radiation risks to patients are
      the carcinogenic and genetic effects. Radiation dosimetry is well established for
      DXA in adults, but there are limited paediatric data available. We report on a
      study to estimate the effective doses (EDs) received by typical 5- and 10-year
      old children using the paediatric scan mode on the Lunar DPX-L bone mineral
      density scanner. Entrance surface doses (ESDs) and percentage depth doses for the
      total body and PA spine scan modes were measured using lithium borate
      thermoluminescent dosemeters (TLDs) located at the surface and distributed at
      various organ locations in anthropomorphic child phantoms. The EDs were
      calculated from the percentage depth doses, amount of each organ irradiated and
      tissue weighting factors. The ESDs were measured to be 6.0 and 0.12 microGy for
      the posteroanterior (PA) spine and total body, respectively. PA spine EDs were
      calculated as 0.28 and 0.20 microSv for the 5- and 10-year-old, respectively.
      Total body EDs were 0.03 and 0.02 microSv for the 5- and 10-year-old children,
      respectively. These results compare with an adult ED of 0.21 microSv for the PA
      spine. They are also more than two orders of magnitude lower than reported ESDs
      and EDs for paediatric chest X-rays. Bone mineral density (BMD) short-term in
      vitro precision was 0.5% and 1% in the 5- and 10-year-old phantoms, respectively.
      In conclusion, the Lunar DPX-L in the paediatric mode has a high precision and
      very low radiation doses, similar to those reported for the adult mode.

PMID- 9245885
TI  - Comparison of two Hologic DXA systems (QDR 1000 and QDR 4500/A).
AB  - Bone mineral content is reliably measured by dual energy X-ray absorptiometry
      (DXA), if manufacturers' recommendations and quality control (QC) procedures are
      followed. Several phantoms (Hologic anthropomorphic spine phantom, the Groupe de
      Recherche et d'Informations sur les Osteoporoses (GRIO) test objects and the
      European semi-anthropomorphic phantoms) were used to evaluate reproducibility,
      linearity, accuracy and spatial resolution of two DXA devices in vitro. These
      parameters were also evaluated in vivo from measurements performed on 120
      volunteer patients. It was found that when one device (a single beam monodetector
      QDR 1000) is replaced by another (a fan beam multidetector QDR 4500/A), the novel
      combination of procedures described here, ensures that the accuracy of DXA study
      results is maintained when both devices are used in succession for the same
      patient. To study the possible responses in clinical situations, the influence of
      bone environment (soft and adipose tissues) was also evaluated. In both systems,
      similar performances (in vitro coefficients of variation of 0.5%) were
      established. At extreme bone density values, slight differences in linearity were
      found, as well as differences in accuracy and spatial resolution. Lumbar spine
      and femoral neck measurements were performed with both systems in 120 volunteers,
      both measurements being made on the same day. The corresponding bone mineral
      density (BMD) values were highly correlated (r2 = 0.985 for lumbar spine and
      0.948 for the femoral neck), and the mean BMD differences were 0.68% and 0.37%
      for each anatomical site, respectively. Although small, these differences add to
      the precision error of the method, which is near 1%. A calibration curve has to
      be obtained in order that both devices can be equally used in regular clinical
      study. We concluded that when a DXA system is replaced by a new one, appropriate
      QC procedures must be strictly observed.

PMID- 9245886
TI  - Methods for transferring patient and plan data between radiotherapy treatment
      planning systems.
AB  - The effectiveness of conformal radiotherapy can ultimately only be assessed by
      the use of clinical trials. As large multicentre clinical trials become more
      widespread, methods of transferring patient and plan data between radiotherapy
      treatment planning systems become increasingly important. In this paper, the
      general strategy for the transfer of data is discussed, and also illustrated with
      reference to two specific systems: TARGET 2 (GE Medical Systems) and VOXELPLAN
      (DKFZ-Heidelberg). The transfer method involves using a computer program to
      translate the data formats used by each of the two systems for CT scans, patient
      outlines, plan information and block descriptions. This paper does not address
      the question of transferring beam data between systems: beam data must first be
      entered separately into both machines. The physical concepts encountered when
      transferring plans are described, with specific reference to the two planning
      systems used. Differences in the strategies used by the two planning systems for
      definition of irregular field shapes are compared. The dose calculations used by
      the two systems are also briefly evaluated. Isodoses produced by VOXELPLAN around
      a circular target volume are found to be up to 3 mm different in location to
      those produced by TARGET 2, owing to the use of a smooth field shape contour as
      opposed to a stepped field shape which closely models the leaves of a multileaf
      collimator. In general, dose distributions generated by both systems are
      comparable, but some differences are found in the presence of large tissue
      inhomogeneities. It is concluded that the transfer of patient and plan data
      between two different treatment planning systems is feasible, provided that any
      differences in field shape definition methods or dose calculation methods between
      the two systems are understood.

PMID- 9245887
TI  - Prenatal diagnosis of an extensive fetal lymphangioma using ultrasonography,
      magnetic resonance imaging and cytology.
AB  - An unusual case of fetal lymphangioma diagnosed before delivery is reported in a
      second trimester pregnant woman. The lymphangioma was suspected at 28 weeks on
      the basis of the ultrasound appearances and progression of the lesions with
      advancing gestation. MRI was used to evaluate the extent and the tissue
      characteristics of the lesions. Cytology of the fluid aspirated from the cystic
      lesions showed abundant lymphocytes and macrophages, confirming the diagnosis of
      a lymphangioma. The parents opted for a pregnancy termination because of the
      rapid growth of the lesions and the poor prognosis. It is suggested that the
      combination of these tests could enable the early diagnosis of these tumours at a
      stage when the lesion is relatively limited and accessible to therapy in utero.

PMID- 9245888
TI  - Bare area abscess: imaging findings and potential communication with the
      mediastinum.
AB  - The bare area of the liver is not usually visualized by standard cross-sectional
      imaging techniques except in patients with ascites or subphrenic collections
      where this area is spared of fluid. We present a case of an abscess in the bare
      area of the liver with imaging findings and demonstration of a communication with
      the mediastinum, not previously described.

PMID- 9245889
TI  - Ultrasound and CT changes of liver parenchyma in acute schistosomiasis.
AB  - Acute schistosomiasis in travellers to endemic regions often remains
      unrecognized. Early diagnosis is important to avoid progression to chronic
      disease. Diagnosis is based on clinical, epidemiological and laboratory data. The
      role of imaging techniques as diagnostic tools remains to be established in acute
      clinical schistosomiasis. We describe hypodense nodules in the liver on
      ultrasound and CT scanning in a patient with acute schistosomiasis (Katayama
      syndrome). To our knowledge this is the first description of nodular hepatic
      lesions in acute schistosomiasis.

PMID- 9245890
TI  - Calcium within a bronchogenic cyst with a fluid level.
AB  - A 38-year-old man presented with a bronchogenic cyst which showed a high calcium
      content. The calcium precipitate layered in the dependent part of the cyst to
      form a fluid level. The CT and MRI findings of this rare case are discussed.

PMID- 9245891
TI  - Rhombencephalosynapsis associated with hand anomalies.
AB  - A case of rhombencephalosynapsis, a very rare disorder characterized by agenesis
      or hypogenesis of the cerebellar vermis and fusion of the cerebellar hemispheres,
      is reported with magnetic resonance imaging features. Radiographs showed
      anomalies in both hands; namely phalangeal hypoplasia and occult polydactyly in
      the right hand and syndactyly in the left, previously unreported in association
      with this disorder.

PMID- 9245892
TI  - Risk of childhood cancer from fetal irradiation: 1.

PMID- 9245893
TI  - Risk of childhood cancer from fetal irradiation: 2.

PMID- 9245894
TI  - Transplantation of retinal pigment epithelial, photoreceptor and other cells as
      treatment for retinal degeneration.

PMID- 9245895
TI  - Light scattering and morphology of cataract formation in transgenic mice
      containing the HIV-1 protease linked to the lens alpha A-crystallin promoter.
AB  - Two constructs of transgenic mice, TG61 and TG72, containing the HIV-1 protease
      linked to the lens alpha A-crystallin promoter develop cataract. The TG61
      construct develop cataract in utero, while the TG72 construct exhibit frank
      opacities on the 24th day (homozygotes) and 26th day (hemizygotes) post natum.
      Polarized light scattering measurements were performed on cortical and nuclear
      sections of TG72 lenses from day 19 to day 26 as a function of scattering angle.
      The parallel components of the scattered light intensity increase gradually
      during opacification, the perpendicular components show very low values from day
      19 to day 22 after which they increase exponentially. Analysis of the scattered
      light intensities yielded parameters describing the size of the protein
      aggregates, the size of the domains exhibiting optical anisotropy/birefringence,
      the difference in refractive index between (a) the protein aggregates and their
      surroundings and (b) the birefringent units and their surroundings. The last
      parameter accounts for the major portion of the increase in lens turbidity. The
      TG72 construct shows normal lens development on day 16. By day 21 the posterior
      cortex shows some disintegration, while the lens is still clear. By day 26 the
      lens nucleus migrates toward the posterior pole and there is a major alteration
      in the cortical fibers. Scanning electron microscopic studies reveal normal fiber
      cell organizations in control animals. In the TG72 construct the fiber cells are
      well organized at 16 days after birth but already develop some slight separation
      in the posterior cortical part of the lens. By post-natal day 21, the nucleus and
      the anterior cortex still exhibit well aligned fiber cell organization, but the
      posterior cortex shows disalignment. By day 26 in the TG72 construct, all areas
      of the lens show complete disintegration of the fiber cells and amorphous masses
      are present throughout. The light scattering parameters describing changes on the
      nanometer scale can be correlated with the changes in lens morphology during
      cataractogenesis that occur on the micrometer scale. In comparison, the light and
      scanning electron microscopic examinations of the postnatal TG61 construct show
      that the lens is severely disrupted and contains completely disintegrated fiber
      cell remnants at an early age.

PMID- 9245896
TI  - Induced refractive anomalies affect chick orbital bone structure.
AB  - Experiments have shown that it is possible to induce ametropias (myopia and
      hyperopia) in the eyes of young animals by distorting early visual experience
      through the use of negative and positive defocussing lenses mounted over the eye.
      Defocus lenses (+15 and -15 diopters) were mounted unilaterally over one eye of
      day old broiler chicks using a contact lens-goggle and velcro combination.
      Refractive states and ocular dimensions were measured by retinoscopy and
      ultrasound during the experiment. On the seventh day the birds were killed after
      which the eyes were removed, weighed and measured with calipers. The remaining
      heads were cleaned of all soft tissue to leave only the bones of the skull. Axial
      and equatorial orbital dimensions were then measured with vernier calipers. The
      frontal bone was prepared for histological analysis and sections were used to
      determine the relative proportions of formed bone to primitive mesenchymal cells.
      Prior to treatment there were no differences in refractive states or dimensions
      of the two eyes. After one week of defocus, the treated eyes were longer or
      shorter as well as more myopic or hyperopic than the contralateral eye by amounts
      close to the powers of the defocussing lenses (-12.3 and +11.8 diopters). Orbital
      sizes varied substantially. Orbital axes of myopic eyes were significantly (P <
      or = 0.05) longer (on average 0.77 +/- 0.23 mm) than the contralateral control
      orbits. The orbital axes associated with the hyperopic eyes were significantly (P
      < or = 0.05) shorter (on average 0.69 +/- 0.18 mm) than the contralateral control
      orbits. Similarly, significant differences (P < or = 0.05) were recorded for a
      variety of equatorial measures (naso-temporal, superior inferior, oblique (nasal
      superior, temporal-superior). Histological analysis reveals that the frontal bone
      of the myopic chick is in a more mature state of development compared to the
      frontal bone of the hyperopic chick. The eyes and orbits of chicks with induced
      ametropias that were allowed to the recover were not significantly different from
      the control eyes and orbits. This study clearly shows that, in chicks, ocular
      refractive development is associated with orbital development and that
      experiments related to growth factors and retinal processing of defocus
      information should also consider growth and development of tissue beyond the
      ocular globe.

PMID- 9245897
TI  - In vitro metabolic competence of the frog retina: effects of glucose and oxygen
      deprivation.
AB  - The metabolic competence and histological integrity of the frog retina in vitro
      were evaluated as a function of the presence/absence of exogenous glucose and of
      oxygen tension. Dark- and light-adapted frog neural retinas were incubated for 1
      8 hr at 23 degrees C in a modified Ringer's-bicarbonate medium under aerobic and
      anaerobic conditions, in the presence and absence of 10 mM glucose. Control
      retinas (+glucose, aerobic conditions) maintained ATP levels comparable to those
      of freshly excised tissue (ave. 17 nmol mg protein-1), produced minimal lactate
      (ave. 0.12 mumol mg protein-1 hr-1), and exhibited normal histology. In the
      absence of any exogenous carbon source, retinas incubated aerobically maintained
      ATP levels, produced lactate, incorporated [3H]acetate into nonsaponifiable
      lipids, and exhibited histology comparable to controls. In the presence of 1 mM
      iodoacetate, aerobic ATP levels declined markedly, with or without exogenous
      glucose. Under anaerobic conditions with glucose present, lactate production
      increased ca. 8.5-fold, while ATP levels were maintained at control levels,
      demonstrating a marked Pasteur effect; under these conditions, retinas exhibited
      only moderate histopathological changes. However, in the absence of both glucose
      and oxygen, ATP levels declined precipitously, with concomitant massive
      cytological deterioration. No major differences in the biochemical measurements
      or histological appearance were observed as a function of light adaptation. These
      results demonstrate the remarkable resilience of the frog retina to anoxia and
      hypoglycemic stress. Aerobically, with or without exogenous glucose, ATP
      production and de novo lipid synthesis are maintained, apparently by recruitment
      of an endogenous carbohydrate substrate (e.g., glycogen).

PMID- 9245898
TI  - Relationship of protein-glutathione mixed disulfide and thioltransferase in H2O2
      induced cataract in cultured pig lens.
AB  - It has been previously shown in H2O2-induced cataract model in the rat lens that
      protein-GSH (PSSG) formation precedes protein-protein disulfide (PSSP)
      conjugation and lens opacity. This elevated PSSG spontaneously reduces to a
      normal level when H2O2 is removed. To verify if thioltransferase (TTase), an
      enzyme that is known in other tissues to dethiolate PSSG, takes part in this
      recovery process, we examined the relationship of PSSG and TTase in this cataract
      model. To ensure enough tissue would be available for various biochemical
      studies, H2O2 induced cataract in pig lens was established and validated with the
      rat lens model. The study was divided into two parts. One part was to examine the
      effect of H2O2 concentration, ranging from 0.1 mM-10 mM, during 24 hr. Another
      part was to study the H2O2 (1.5 mM) induced cataract progression and recovery,
      parallel to the long-term study in rat lenses reported previously. These lenses
      were compared for transparency, wet weight, GSH, PSSG levels and the activity of
      two redox regulating enzymes, glutathione reductase (GR) and TTase. For the most
      part, pig lens responded to oxidation parallel to the rat lens except that a
      higher concentration of H2O2 was needed to achieve the same results. Damage
      induced by H2O3 was concentration dependent. In general TTase activity and GSH
      level were depleted with a concomitant increase in PSSG. The D50 (50% damage) for
      GSH in pig lens was 1.5 mM H2O2 (0.5 mM for rat lens) which was chosen for
      further studies in cataract progression and recovery. At 1.5 mM H2O2, pig lens
      showed superficial opacity within 24 hr and deeper cortical opacity in 48 hr. The
      pre-exposed lens became less cloudy when H2O3 was removed from the medium.
      Incubation of the lens in 1.5 mM H2O2 for one day also induced 50% GSH depletion
      and four fold PSSG elevations. This accumulated PSSG was dethiolated
      spontaneously in the absence of H2O2, similar to the findings in the rat lens and
      human lens models. In contrast protein-cysteine (PSSC) showed little change and
      did not respond to the recovery condition. TTase lost 50% activity in these
      lenses during 24-hr H2O3 exposure but regained most of it under recovery. The
      study on rat lens showed similar results as before, therefore only data on the
      relationship of TTase activity to PSSG level during cataract development and
      recovery is reported here. It was found that in the H2O2 (0.5 mM)-exposed rat
      lenses, the TTase activity was depleted but PSSG accumulation was accelerated
      within 8 hr. Both recovered quickly (within 8 hr) as soon as the oxidant was
      removed. Therefore, protein thiolation and dethiolation processes in the cultured
      rat or pig lenses display a mirror image with the activity pattern of TTase.
      Based on the close relationship between lens TTase and PSSG indicated above, it
      is speculated that TTase may regulate PSSG and maintain it at a low concentration
      in situ. This repair process may contribute to the improved transparency during
      recovery. Further studies are planned to substantiate this hypothesis.

PMID- 9245899
TI  - Experimental erbium: YAG laser photoablation of trabecular meshwork in rabbits:
      an in-vivo study.
AB  - Photoablative laser trabecular surgery has been proposed as an outflow-enhancing
      treatment for open-angle glaucoma. The aim of the study was to investigate the
      time course of repair response following low-thermal Erbium: YAG laser trabecular
      ablation. In 20 anaesthetized rabbits gonioscopically controlled ab-interno
      photoablation of the ligamenta pectinata and underlying trabecular meshwork (TM)
      was performed with a single-pulsed (200 microseconds) Erbium: YAG (2.94 microns)
      laser. The right eye received 12-15 single laser pulses (2 mJ) delivered through
      an articulated zirconium fluoride fiberoptic and a 200 microns (core diameter)
      quartz fiber tip, the left unoperated eye served as control. At time intervals of
      30 minutes, 2, 10, 30, and 60 days after laser treatment, eyes were processed for
      light- and scanning electron microscopy. The applied energy density of 6-4 J cm-2
      resulted in visible dissection of the ligamenta pectinata and reproducible
      microperforations of the TM exposing scleral tissue accompanied by blood reflux
      from the aqueous plexus. The initial ablation zones measured 154 +/- 36 microns
      in depth and 45 +/- 6 microns in width. Collateral thermal damage zones were 22
      +/- 8 microns. At two days post-operative, ablation craters were still blood- and
      fibrin-filled. The inner surface of the craters were covered with granulocytes.
      No cellular infiltration of the collateral thermal damage zone was observed. At
      10 days post-operative, progressive fibroblastic proliferation was observed,
      resulting in dense scar tissue formation with anterior synechiae, proliferating
      capillaries and loss of intertrabecular spaces inside the range of former laser
      treatment at 60 days post-operative. Trabecular microperforations were closed 60
      days after laser treatment in all rabbits. IOP in treated and contralateral eyes
      did not significantly change its level during whole period of observation. Low
      thermal infrared laser energy with minimal thermal damage to collateral
      structures could not effectively prevent early scarring of trabecular surgery in
      rabbits.

PMID- 9245900
TI  - Metabolism of anandamide, an endogenous cannabinoid receptor ligand, in porcine
      ocular tissues.
AB  - Anandamide (arachidonylethanolamide) is an endogenous ligand for cannabinoid
      receptors, and exerts various cannabimimetic activities. Since cannabinoids and
      anandamide were pharmacologically active with the eye, we examined metabolism of
      anandamide in a variety of porcine ocular tissues. In the presence of
      ethanolamine, [14C]arachidonic acid was converted to [14C]anandamide by a
      homogenate of retina, choroid, iris, optic nerve and lacrimal gland with a
      specific enzyme activity of 1.9-4.2 nmol min-1 mg-1 protein at 37 degrees C. On
      the other hand, [14C]anandamide was hydrolysed to [14C]arachidonic acid by a
      homogenate of each tissue with a specific enzyme activity of 1.2-3.5 nmol min-1
      mg-1 protein. Thus, both activities of anandamide synthase and hydrolase were
      found in these ocular tissues. As for the subcellular distribution, the two
      enzyme activities were mostly recovered in particulate fractions rather than the
      cytosol. With the retina microsome palmitic acid was converted to its
      ethanolamide at a lower rate than arachidonic acid, and palmitoylethanolamide was
      less active than anandamide as a substrate for the hydrolase.

PMID- 9245901
TI  - Histamine induced contraction of human ciliary muscle cells.
AB  - In cultured human ciliary muscle cells we previously showed that histamine, via
      an H1 receptor, stimulates the production of inositol phosphates and mobilization
      of intracellular calcium. We further investigated in this study whether histamine
      would cause contraction of human ciliary muscle cells. Photomicrographs were
      taken of the ciliary muscle cells before and after exposure to histamine. Cross
      sectional surface area of the cells was quantified using image analysis software.
      A decrease in cross sectional surface area was interpreted as an indication of
      cell contraction. The results of this study indicated that histamine (10(-6) M
      10(-4) M) caused contraction of human ciliary muscle cells in a concentration
      dependent fashion. The effect of histamine was mediated by the H1 receptor
      subtype since the histamine effect was antagonized by 10(-6) M chlorphentramine
      (an H1 receptor subtype selective antagonist) but not by 10(-6) M cimetidine (H2
      antagonist) or thioperamide (H3 antagonist). The phospholipase C (PLC) inhibitor,
      U73122 (10(-6) M) and the intracellular calcium store depleting agent
      thapsigargin (10(-6) M) both prevented the histamine induced contraction,
      demonstrating that the activation of PLC and the intracellular calcium release
      were the key steps necessary for contraction. Our data indicate that in ciliary
      muscle cells, histamine, via an H1 receptor, activates PLC and increases
      intracellular calcium, which subsequently causes contraction of the cells.

PMID- 9245902
TI  - Expression of 17 beta-hydroxysteroid dehydrogenase type IV in chick retinal
      pigment epithelium.
AB  - Retinal pigment epithelium (RPE) has essential roles that maintain functions of
      the neural retina. Previously, we described that the 3b5 monoclonal antibody (3b5
      mAb) recognized the RPE cells in the chick embryonic eye. In the present study, a
      gene coding for the 3b5 antigen has been cloned and sequenced. A 10-day-old
      embryonic RPE cDNA library was constructed in lambda Uni-ZAP XR, and screened
      with the 3b5 mAb as a probe. The complete nucleotide sequence of the antigen
      recognized by the 3b5 mAb was obtained. The cDNA encodes a 735 amino acid protein
      with a calculated molecular mass of 80,147 Da. The deduced amino acid sequence
      shares 72% identity with the human 17 beta-hydroxysteroid dehydrogenase (17 beta
      HSD) type IV. Northern blot analysis detected a 2.9 kb transcript.
      Immunohistochemical and in-situ hybridization studies revealed that 17 beta-HSD
      type IV was preferentially expressed in the RPE cells. The expression of steroid
      metabolizing enzymes in the RPE cells is able to create estrogenic environment,
      which may have a role of maintenance of the neural retina.

PMID- 9245903
TI  - Oxidation products of 3-hydroxykynurenine bind to lens proteins: relevance for
      nuclear cataract.
AB  - 3-Hydroxykynurenine (3OHKyn), present as a human lens UV filter, has also been
      implicated as a carcinogen and neurotoxin. It has been suggested that oxidation
      of 3OHKyn is involved in each of these effects. In the presence of oxygen, 3OHKyn
      has been found to react with bovine crystallins, to give brown-coloured products
      (Stutchbury and Truscott, 1993). In this study the roles of UV-light, pH,
      glutathione and oxygen were examined, with the objective of determining how these
      factors may affect the binding of 3OHKyn to crystallins under the conditions
      found within the lens itself. The presence of oxygen was found to be an important
      parameter for determining the extent to which 3OHKyn reacts with protein, and
      when it was totally excluded, little modification was observed. UV-light was not
      required for activation, but was found to augment the extent of modification and
      cross-linking, while an elevated pH, which is known to accelerate the rate of
      3OHKyn oxidation, did not markedly increase the extent of reaction with the
      crystallins. 3OHKyn binding was accompanied by crystallin aggregation,
      pigmentation, and development of non-tryptophan fluorescence, all of which have
      been associated with cataract formation. The inclusion of glutathione, a
      ubiquitous antioxidant, in reaction mixtures resulted in a delayed onset of
      crystallin modification. This effect was apparent at concentrations of
      glutathione greater than 1 mM. When glutathione levels fell below 1 mM,
      crystallins became modified by 3OHKyn. Since lens glutathione concentrations
      decrease with age, and are known to be lower in the lens nucleus than the cortex,
      this region appears particularly vulnerable to modification by this UV filter.
      Thus, whilst the other human lens UV filters, kynurenine (Kyn) and 3
      hydroxykynurenine glucoside (3HKG), appear to require activation by UV-light in
      order to react with proteins, 3OHKyn can modify crystallins in the absence of
      light, under conditions of low oxygen tension, and in the presence of glutathione
      concentrations found in the nucleus of an aged lens. Its reactivity is increased
      in the presence of both light and oxygen. The contributions of these parameters
      to the reactivity of 3OHKyn are discussed, with respect to the aetiology of
      senile nuclear cataract.

PMID- 9245904
TI  - Autoregulation of human optic nerve head circulation in response to increased
      intraocular pressure.
AB  - The following experiments were undertaken to determine if blood flow is
      maintained by autoregulation in the human optic nerve head when circulation is
      challenged by elevated intraocular pressure, and to determine if the presence or
      absence of autoregulation is universal. Laser Doppler flowmetry was used to
      determine the average velocity, the number of moving erythrocytes, and the volume
      of flow in the capillary bed of the optic disc. These parameters were measured in
      10 subjects at spontaneous levels of intraocular pressure (IOP), and at pressures
      artificially elevated to 25, 35, 45 and 55 mm Hg with a scleral suction cup. Four
      subjects (two who showed autoregulation and two who did not) were studied on six
      additional occasions to determine consistency of the findings. In these same four
      subjects a second location on the disc was also measured on six occasions to
      determine if the IOP-effect on blood flow varied by location. Of the 10 subjects
      initially studied, seven maintained the baseline level of blood flow over the
      lower part of the range of elevated intraocular pressure (evidence of
      autoregulation), but showed a decline in flow by the time IOP reached 45 or 55 mm
      Hg. Two subjects showed a linear decline in blood flow beginning with the
      smallest increment of elevation of IOP (no autoregulation), and one showed an
      uninterpretable result. The two individuals who showed the linear decline and two
      of those who showed efficient autoregulation were remeasured, and each showed
      consistently the same pattern as before when restudied on six different occasions
      each. However, at a different location on their discs, autoregulation was
      manifest in all of these four individuals. When challenged by elevated IOP, the
      optic nerve head typically maintains a steady-blood flow over a range of IOP, but
      fails to maintain the same flow by the time IOP reaches 45 or 55 mm Hg. Some disc
      locations, at least in some individuals, do not show this autoregulation, but
      exhibit a decline in blood flow linearly related to IOP, even with the modest
      elevation of IOP.

PMID- 9245905
TI  - Inducible expression of Na+/myo-inositol cotransporter mRNA in anterior
      epithelium of bovine lens: affiliation with hypertonicity and cell proliferation.
AB  - Bovine lenses were pretreated with physiological (314 +/- 6 mosm) or hypertonic
      medium (> 450 mosm) for 20 hours prior to introduction of the lenses into
      modified Ussing chambers (providing a leakproof seal at the lens equator). The
      anterior (epithelial-containing) and posterior (cell-free) aspects of the mounted
      intact lens could thus be independently bathed with myo-[3H]inositol. Myo
      inositol uptake as a function of concentration across the anterior aspect was
      indicative of an active carrier-mediated component and at high concentration,
      significant myo-inositol influx due to passive diffusion. Myo-inositol uptake was
      markedly stimulated across the anterior aspect and inhibitable by ouabain but not
      stimulated across the posterior aspect, when lenses were exposed to hyperosmotic
      medium by the addition of raffinose or sodium chloride. Myo-inositol rapidly
      desaturates across both aspects of the lens consistent with its efflux being
      largely a function of passive diffusional leakout from the extracellular space.
      In order to corroborate the apparent hypertonic-induced upregulation of gene
      expression inferred by kinetic analysts, the level of Na+/myo-inositol
      cotransporter mRNA was determined by reverse transcription and quantitative PCR
      using harvested anterior epithelial cells from intact lenses exposed to
      physiologic or hypertonic medium for 20 hours. RNA samples were microextracted
      from both the central and equatorial regions of the lenticular epithelium of the
      anterior lens capsule. The abundance of Na+/myo-inositol cotransporter mRNA was
      similar from epithelium of the central zone irrespective of medium tonicity but
      was markedly elevated from the equatorial zone of osmotically-stressed lenses.
      While both the quiescent epithelial cells of the central region and actively
      dividing epithelial cells of the equatorial zone of the intact lens express
      Na+/myo-inositol contransporter mRNA, only the equatorial epithelium responds to
      hypertonic insult with enhanced uptake of myo-inositol due to increased
      transcription of the Na+/myo-inositol cotransporter gene, suggesting a possible
      role for the state of cell proliferation.

PMID- 9245906
TI  - Cellular retinaldehyde binding protein in developing retinal astrocytes.
AB  - Cellular retinaldehyde binding protein (CRALBP) is present in Muller glia and in
      cells of the retinal pigment epithelium, but we have recently observed CRALBP
      like immunoreactivity near the inner limiting membrane in the newborn mouse
      retina. The present study has examined whether this protein is present in
      developing retinal astrocytes. Retinal tissue was collected at various embryonic
      and postnatal ages and in adulthood. Tissue for immunohistochemistry was fixed by
      immersion in 4% paraformaldehyde and immunostained using rabbit polyclonal
      antisera to CRALBP or glial fibrillary acidic protein (GFAP), while fresh tissue
      was homogenized for Western analysis. Specificity of the antiserum for the 33 kDa
      protein was shown in retinal homogenates by immunoblotting, with expression of
      the protein increasing steadily from E15.5 through adulthood. Immunostaining of
      sections from fetal eye-cups revealed faint labeling of cells in the optic nerve,
      with progressive migration of CRALBP-immunoreactive cells into the retina at the
      inner limiting membrane during the perinatal period. By the day of birth, these
      cells were intensely immunoreactive, showing a morphology characteristic of
      migrating astrocytes. These CRALBP-immunoreactive cells mimicked the progressive
      infiltration of GFAP-positive astrocytes which are known to migrate into the
      retina from the optic nerve head, many of which were double-labeled with GFAP.
      Their distribution across the retina is distinct from that of the lighter
      staining Muller glial somata during these stages, and they are not misidentified
      Muller glial endfeet. Astrocytes are only transiently CRALBP-immunoreactive, no
      longer containing the protein after the second post-natal week. Preincubation of
      the antiserum with purified CRALBP abolished all staining of astrocytes. Coupled
      with the fact that only a single (approximately 33 kDa) molecular weight protein
      is labeled by the antiserum, it was concluded that retinal astrocytes contain
      CRALBP during a limited period of development.

PMID- 9245907
TI  - Mechanisms of adrenergic agonist induced allergy bioactivation and antigen
      formation.
AB  - Reduction of elevated intraocular pressure with alpha 2 agonists has proved to be
      an exciting new therapeutic approach for the treatment of glaucoma. We have
      studied the chemical reactivities of several alpha 2 agonists and known allergens
      to elucidate the origin of the observed ocular allergic response to the alpha 2
      agonist apraclonidine. The oxidation potentials of clonidine, apraclonidine,
      brimonidine, and two known allergens, amodiaquine, and epinephrine, were measured
      vs. a standard calomel electrode.. Agents that were oxidatively labile were
      treated with both chemical and enzymatic oxidants. Clonidine and brimonidine
      proved to be oxidatively stable in sharp contrast to apraclonidine which had an
      oxidation potential similar to that observed with epinephrine and amodiaquine,
      two known allergy-inducing agents. In addition, two glutathione-apraclonidine
      conjugates formed by the in-situ reaction of glutathione with an enzymatically
      oxidized apraclonidine intermediate were isolated and their structures determined
      using spectroscopic methods. The structures were shown to be analogous to those
      obtained with amodiaquine and epinephrine. Apraclonidine, like amodiaquine and
      epinephrine, possesses a hydroquinone-like subunit and can be readily oxidized
      and conjugated with thiols modeling well known hapten-forming reactions.
      Brimonidine, like clonidine, lacks the hydroquinone subunit and does not undergo
      the thiol conjugation reactions.

PMID- 9245908
TI  - Herpes simplex virus type-1 infection of corneal epithelial cells induces
      apoptosis of the underlying keratocytes.
AB  - The purpose of this study was to determine whether primary corneal infection with
      Herpes simplex virus (HSV)-1 induces keratocyte apoptosis in the rabbit. New
      Zealand white rabbit eyes were inoculated with HSV-1 strain 17 Syn+. Rabbits that
      developed slit lamp signs of epithelial infection were killed between 12 and 120
      hr post infection. One cornea of each animal was fresh-frozen for TUNEL assay to
      detect DNA fragmentation in situ. The other cornea was fixed for transmission
      electron microscopy (TEM). Mechanical scrape wounded rabbit corneas were included
      as positive controls. DNA fragmentation consistent with apoptosis was detected in
      anterior keratocytes of corneas at 18, 24, and 48 hr after primary infection with
      HSV-1 and 2 hr after an epithelial scrape, but not in unwounded control corneas.
      Electron microscopic evidence of keratocyte apoptosis that included chromatin
      condensation, chromatin fragmentation, and cellular blebbing with formation of
      membrane bound cell fragments was detected in mechanical scrape wounded corneas
      and infected rabbit corneas at 12, 18, 24, 48, and 120 hr after infection, but
      not in unwounded control corneas. This study suggests that anterior stromal
      keratocyte apoptosis occurs following primary HSV-1 infection of the corneal
      epithelium. Previous studies have demonstrated that corneal epithelial scrape
      wounds induce apoptosis in the underlying keratocyte cells. We hypothesize that
      soluble mediators released by epithelial injury mediate anterior keratocyte
      apoptosis and that one of the physiologic functions of this epithelial-stromal
      apoptosis system is to limit viral extension.

PMID- 9245909
TI  - Multiple kinesin family members expressed in teleost retina and RPE include a
      novel C-terminal kinesin.
AB  - Kinesins comprise a large superfamily of microtubule-based motor proteins,
      individual members of which mediate specific types of motile processes. To
      identify kinesin family members (KIFs) that are critical to retinal function and
      thus to vision, a reverse transcriptase polymerase chain reaction (RT-PCR)
      cloning strategy was used to isolate putative KIFs expressed in the neural retina
      and retinal pigmented epithelium (RPE) of the striped bass, Morone saxatilus.
      Eleven fish KIFs (FKIFs) were isolated from neural retina and six of the same
      FKIFs were also isolated from RPE. One of the KIFs identified in this screen,
      FKIF2, was the most prevalent clone detected both in the retina (41% of clones)
      and RPE (72% of clones). Based on predicted amino acid sequence homology within
      the motor domain, seven of the FKIFs have been tentatively assigned to known
      kinesin families: the kinesin heavy chain family (FKIF1, 5 and 9), the
      unc104/KIF1 family (FKIF3 and 8), the KIF2 family (FKIF4), and the cKIF family
      (FKIF2). Northern blot analysis revealed that each detectable FKIF exhibited a
      unique tissue-specific expression pattern. Since FKIF2 was more highly expressed
      in retina than in any other tissue tested, including brain, and was the most
      abundant KIF message expressed in both retina and RPE, it was examined in more
      detail and the complete approximately 2.3 kb open reading frame for FKIF2 was
      cloned and sequenced. The predicted amino acid sequence indicates that FKIF2 has
      a C-terminal motor domain, and thus is a member of the cKIF family. FKIF2 is only
      36.5% identical at the amino acid level to the most closely related cKIF in the
      database, suggesting that FKIF2 may be a novel member of this family. Antibodies
      raised against a unique peptide specific to FKIF2 recognize an approximately 80
      kd protein in homogenates of retina, RPE, brain and kidney. The pronounced
      expression of FKIF2 in retina and RPE suggests that FKIF2 may play an important
      role in microtubule-dependent motile events in these two tissues.

PMID- 9245911
TI  - Properties of electrochemically active components in mammalian vitreous humor.
AB  - Antioxidants are considered to have important roles in protecting the eye against
      radiation, oxygen toxicity and other threats. Several water-soluble
      electrochemically-active compounds that might function as antioxidants in
      vitreous humor of rabbit, rat and bovine eyes were identified and quantitated. In
      that the rat is a nocturnal animal species and the other two are diurnal, the
      results allow a tentative evaluation on the comparative physiology of light-dark
      behavior patterns that influence this ocular fluid. All analyses were performed
      by HPLC with electrochemical detection. The utility of this approach is that
      components of vitreous humor can be identified by their retention time and by
      their characteristic response when the voltages of the two sensing electrodes are
      progressively brought together. Four compounds regarded as functional
      antioxidants in the animal kingdom were identified and quantitated. Other
      antioxidants known to be present in several biological fluids are not present at
      detectable or significant levels in vitreous humor; metabolites or precursors of
      these might be present in trace quantities.

PMID- 9245910
TI  - An animal model for cidofovir (HPMPC) toxicity: intraocular pressure and
      histopathologic effects.
AB  - Intravitreal cidofovir has been shown to be a long acting and highly efficacious
      treatment for CMV retinitis; however decrease in IOP is an adverse effect. We
      wanted to determine the effect of cidofovir on intraocular pressure (IOP) in the
      guinea pig, and rabbit eye to develop an animal model of cidofovir induced ocular
      hypotony and to study the histopathology of this toxicity. Twenty-eight guinea
      pig eyes were injected with cidofovir yielding final intravitreal concentrations
      of 25, 200, 625 and 2000 micrograms ml-1. Eighteen eyes of pigmented rabbits were
      injected with cidofovir yielding final intravitreal concentrations of 625 and
      2000 micrograms ml-1. A carefully calibrated low volume displacement manometer
      system using a micro-transducer was used to determine the IOP measurements in the
      guinea pig and rabbit eyes. Histology was evaluated using light and electron
      microscopy. Injection of 6.25 micrograms of cidofovir intravitreally (vitreous
      concentration of 25 micrograms ml-1) is the highest non-toxic dose in the guinea
      pig; the IOP was unchanged at two and four weeks after injection with this dose;
      histologically the eyes were normal. A single injection of 50 micrograms of
      cidofovir intravitreally (vitreous concentration of 200 micrograms ml-1) caused a
      long lasting (9.3 mmHg) decrease in IOP (approximately 50% of baseline). At this
      dose there were only mild and variable histologic changes in the ciliary body and
      the retina. Higher doses of 156.25 micrograms and 500 micrograms of cidofovir
      (vitreous concentrations of 625, and 2000 micrograms ml-1, respectively) caused
      moderate to severe ciliary body and retinal changes. In rabbit eyes there was a
      mild but statistically insignificant pressure drop with doses of 875 micrograms
      cidofovir intravitreally (vitreous concentration of 625 micrograms ml-1); retina
      was within normal limits after injection with this dose, there were mild changes
      in the ciliary body. There was a total destruction of ciliary body and loss of
      nonpigmented epithelial cells with injections of 2800 micrograms of cidofovir
      intravitreally (vitreous concentration of 2000 micrograms ml-1): retina was
      relatively well preserved. The guinea pig eye shows similar reduction in IOP and
      ciliary body changes as are seen in the human eye after intravitreal cidofovir
      and also appears to have a similar dose-response curve. However, the reduction of
      IOP caused by cidofovir occurs in the guinea pig eye at a concentration 40 times
      higher than was observed in the human eye.

PMID- 9245912
TI  - The role of soluble proteins in generating aqueous outflow resistance in the
      bovine and human eye.
AB  - Previous research has shown that wash-out in bovine and primate eyes can be
      greatly reduced by perfusing with buffer containing 5-15% serum. It was suggested
      that protein diffusion from the iris root might raise the in vivo protein
      concentration in the trabecular meshwork to a level much higher than in the
      anterior chamber. In this study, we investigated the protein concentration in
      effluent from the outflow pathways in bovine and human eyes, its possible
      relationship to wash-out, and whether the reduction of wash-out was caused by a
      bulk protein effect. Bovine and human eyes were placed under silicone oil and
      perfused with buffer. Outflow facility was continuously determined while effluent
      was periodically collected from the surface of the eye, and the soluble protein
      concentration in the effluent was determined. Separate studies were conducted
      perfusing either albumin or gamma-globulin through bovine eyes. Theoretical
      models were developed to study the transport of protein into the perfusion fluid.
      In the bovine eyes, the initial protein concentration in the collected effluent
      was approximately 1% that of serum, much lower than the 10-15% buffer in serum
      required to prevent wash-out. Furthermore, the rate of change of outflow facility
      showed a different dependence on perfused volume than did the protein
      concentration. Human eyes showed a much higher level of protein in the perfusate,
      that decayed over a much longer time period. A statistically significant
      correlation existed between outflow resistance and soluble protein concentration
      in both bovine and human eyes. However, modelling studies suggested that this
      correlation might be due to flow resistance setting the flowrate which then
      determines the protein concentration of the effluent. Separate experiments
      indicated that the decreased rate of wash-out caused by perfusion of 10-15% serum
      in buffer was not due to either albumin or gamma-globulin alone. These results
      suggest that the reduction of wash-out observed in previous studies when serum
      proteins were perfused through bovine and monkey eyes was not due to the general
      level of serum proteins but may instead be due to interactions of a particular
      protein(s).

PMID- 9245913
TI  - A possible role of endogenous inhibitor for nitric oxide synthesis in the bovine
      ciliary muscle.
AB  - The present experiments were designed to investigate the possible role of
      endogenous methylarginine derivatives such as NG-monomethyl-L-arginine,
      asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine
      for the nitric oxide synthesis in the bovine ciliary muscle. The contents of
      asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine
      in the bovine ciliary muscle were determined to be 370.2 +/- 27.6 (n = 5) and
      182.4 +/- 22.9 (n = 5) pmoles g-1 wet weight, respectively by means of the
      automated high-performance liquid chromatography. NG-Monomethyl-L-arginine was
      below the assay limits. On the basis of the total tissue water content (0.792 +/-
      0.006 ml g-1 wet weight, n = 14), the concentrations of asymmetrical NG,NG
      dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine were tentatively
      estimated to be (4.7 +/- 0.3) x 10(-7) M (n = 5) and (2.3 +/- 0.3) x 10(-7) M (n
      = 5), respectively. A23187 (10(-7)-3 x 10(-4) M) produced a concentration
      dependent relaxation of the ciliary muscle strips which had been contracted with
      10(-5) M carbachol. Authentic asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-6)
      3 x 10(-4) M), but not symmetrical NG,N'G-dimethyl-L-arginine (3 x 10(-4) M),
      inhibited the 10(-6) M A23187-induced relaxation in a concentration-dependent
      manner. The inhibition with asymmetrical NG,NG-dimethyl-L-arginine (10(-4) M) was
      reversed by an addition of 3 x 10(-3) M L-arginine, but not by 3 x 10(-3) M D
      arginine. The A23187 (10(-6) M)-induced relaxation was enhanced by 3 x 10(-3) M L
      arginine or superoxide dismutase (50 U ml-1), whereas it was inhibited by carboxy
      PTIO (3 x 10(-4) M), a scavenger of nitric oxide, or methylene blue (10(-5) M),
      an inhibitor of guanylate cyclase. The carbachol-induced contraction was enhanced
      by asymmetrical, NG,NG-dimethyl-L-arginine (10(-5) M) and inhibited by 3 x 10(-3)
      M L-arginine. Any effect of prostanoid formation during the A23187-induced
      relaxation was ruled out by using indomethacin (10(-5) M). Sodium nitroprusside
      (10(-5) M), a donor of nitric oxide, also produced a relaxation, which was
      inhibited by methylene blue (10(-5) M) or carboxy-PTIO (3 x 10(-4) M) and was
      augmented by superoxide dismutase (50 U ml-1), but unaffected by asymmetrical
      NG,NG-dimethyl-L-arginine (3 x 10(-4) M) or L-arginine (3 x 10(-3) M). These
      results lead us to speculate that the nitric oxide synthesized endogenously from
      L-arginine may play a role for mediating relaxation of the bovine ciliary muscle
      and that the endogenous asymmetrical NG,NG-dimethyl-L-arginine may be involved in
      inhibiting the biosynthesis of nitric oxide when there are increased
      intracellular concentrations of the methylarginine under certain circumstances.

PMID- 9245914
TI  - Atropine reduces but does not eliminate the age-related decline in perfusion
      outflow facility in monkeys.
AB  - Accommodative amplitude and outflow facility decline with age in rhesus monkeys
      and humans. In monkeys, there is an age-related reduction in ciliary muscle (CM)
      mobility due to stiffening of its posterior and outer attachments. Since the CM
      inserts into the trabecular meshwork (TM) and CM contraction deforms the TM so as
      to increase outflow facility, we asked whether the age-related decline in outflow
      facility observed in anesthetized monkeys is consequent to the age-related
      reduction in CM mobility. One eye of 19 pentobarbital-anesthetized rhesus monkeys
      aged 4-24 years underwent 2-level constant pressure perfusion of the anterior
      chamber (AC) for 40 min to measure baseline total outflow facility. Both eyes
      then received 100 micrograms of atropine, given topically to the central cornea.
      The AC of the second eye was cannulated 40 min after atropine treatment. Facility
      was measured simultaneously in both eyes for 40 min beginning 45 min after
      atropine treatment. Baseline facility declined with age by -0.0160 +/- 0.0059
      microliters min-1 mmHg-1 yr-1 (P = 0.009). The average facility at baseline was
      approximately 50% higher in the youngest (ages 4-10 years) compared to the oldest
      (ages 21-25 years) animals (P < or = 0.03). Following atropine facility decreased
      by approximately 25% in the youngest monkeys (N.S.), but not at all in the oldest
      animals when compared to baseline. Thus, the age-related facility decline
      persisted after atropine in both eyes, but was not as dramatic as prior to
      atropine (-0.0092 +/- 0.0050 [P < or = 0.09] and -0.0078 +/- 0.0044 [P < or =
      0.10] microliter min-1 mmHg-1 yr-1 respectively). Apparently, atropine inhibits
      facility-relevant anesthetic-induced ciliary muscle tone to a greater extent in
      younger than in older monkeys, presumably because stiffening of the posterior and
      outer attachments of the CM in the older animals has already reduced its ability
      to move and thereby deform the TM. The inability of atropine to completely
      eliminate the age-related facility decline indicates the presence of atropine
      independent, facility-relevant age-dependent changes in the TM itself, such as
      loss of cells or build-up of extracellular material.

PMID- 9245915
TI  - Natural and imposed astigmatism and their relation to emmetropization in the
      chick.
AB  - This study investigated the ocular response of young chicks to astigmatic errors
      imposed by spectacle lenses and as a related issue, we examined the nature and
      prevalence of astigmatism in young chicks, and its relation to corneal
      development and natural emmetropization. Normal hatchling chicks exhibited
      significant against-the-rule refractive astigmatism (approx. 8 D) of which 60-90%
      was corneal. Both types of astigmatism decreased in magnitude with normal corneal
      development as part of emmetropization. The apparent association with corneal
      growth is consistent with two further observations: (1) that smaller corneas,
      induced by constant light rearing, had higher than normal astigmatism (1.5 D
      greater at 15 days), (ii) that enlarged corneas, due to form deprivation, had
      reduced astigmatism (2.4 D less). When astigmatism was artificially imposed with
      (+/-10 DC spectacle lenses), altered ocular growth patterns were observed,
      although the changes were not consistent with the chicks having emmetropized to
      the imposed astigmatism. Irrespective of the axis setting used in positioning the
      lenses (45 degrees, 90 degrees, 180 degrees), eyes became hyperopic with +10 DC
      lenses (+8.8 +/- 1.3 D), and became slightly myopic with 10 DC lenses (-1.8 +/-
      1.9 D). These refractive changes are consistent with the chicks having
      emmetropized to the more myopic meridian rather than the equivalent mean
      spherical error imposed (responses of control groups to +5 D and -5 D spherical
      lenses were +5.2 +/- 1.0 D and -5.1 +/- 0.8 D resp.). The same was true for
      chicks first prevented from accommodating by prior ciliary nerve section, except
      for one group wearing the 10 DC lens at 45 degrees axis where astigmatic changes
      consistent with partial compensation were seen, although this may represent an
      artefact of the surgery. These results argue against 'astigmatic emmetropization'
      as a normal phenomenon. Also consistent with this finding was the lack of
      significant astigmatic changes with accommodation-stimulating and inhibiting
      drugs (nicotine and vercuronium resp.), for normal chicks. These results imply
      that accommodation, while the most likely mechanism for astigmatic
      emmetropization, has little capacity to compensate for imposed astigmatic
      focussing errors.

PMID- 9245916
TI  - The human lens possesses acetylcholine receptors that are functional throughout
      life.

PMID- 9245917
TI  - Location and exposure of hydrophobic surfaces in relation to an 'open' micellar
      quaternary structure of alpha-crystallin.

PMID- 9245918
TI  - The presence of sigma receptor subtypes in bovine retinal membranes.

PMID- 9245919
TI  - Endoscopic sphincterotomy in the young patient: is there cause for concern?

PMID- 9245920
TI  - The clinical relevance of strain types of Helicobacter pylori.

PMID- 9245921
TI  - Trauma and the gut: interactions between stressful experience and intestinal
      function.

PMID- 9245922
TI  - Short segment Barrett's oesophagus: prevalence, diagnosis and associations.
AB  - BACKGROUND: Prevalence of short segment Barrett's (SSB) oesophagus, defined as
      the absence of macroscopic Barrett's but histologically identifiable intestinal
      metaplasia, has been reported to be 18% based on haematoxylin and eosin (H&E)
      staining. AIMS: To define the prevalence of SSB oesophagus using H&E and alcian
      blue staining and to determine whether SSB oesophagus is associated with
      inflammation at the gastro-oesophageal junction (GOJ). SUBJECTS: Consecutive
      patients (n = 158) presenting for endoscopy completed a structured interview.
      METHODS: Two biopsy specimens taken from the GOJ were stained with H&E, alcian
      blue and Giemsa. A third specimen was obtained from the distal oesophagus.
      Intestinal metaplasia was diagnosed if goblet cells were definitely identified by
      two independent observers. RESULTS: SSB oesophagus was present in 46 (prevalence
      36%, 95% confidence interval (CI) 28.5-43.5) using alcian blue staining. If H&E
      had been the sole staining method used, 50% cases of intestinal metaplasia would
      have been overlooked. There were no cases of intestinal metaplasia identified by
      H&E but missed by alcian blue staining. Logistic regression analysis identified
      age (odds ratio (OR) per decade 1.03, 95% CI 1.01-1.06), histological
      oesophagitis (OR 3.2, 95% CI 1.4-7.2) and inflammation at the gastrooesophageal
      junction (OR 5.9, 95% CI 2.2-15.6) as independent risk factors for SSB
      oesophagus. CONCLUSION: Unrecognised SSB oesophagus is highly prevalent in
      patients presenting for diagnostic upper endoscopy if alcian blue staining is
      applied.

PMID- 9245923
TI  - Decision analysis in the management of duodenal adenomatosis in familial
      adenomatous polyposis.
AB  - BACKGROUND: Patients with familial adenomatous polyposis are not only at high
      risk of developing adenomas in the colorectum but a substantial number of
      patients also develop polyps in the duodenum. Because treatment of duodenal
      polyps is extremely difficult and it is unknown how many patients ultimately
      develop duodenal cancer, the value of surveillance of the upper digestive tract
      is uncertain. AIMS: (1) To assess the cumulative risk of duodenal cancer in a
      large series of polyposis patients. (2) To develop a decision model to establish
      whether surveillance would lead to increased life expectancy. METHODS: Risk
      analysis was performed in 155 Dutch polyposis families including 601 polyposis
      patients, and 142 Danish families including 376 patients. Observation time was
      from birth until date of last contact, death, diagnosis of duodenal cancer, or
      closing date of the study. RESULTS: Seven Dutch and five Danish patients
      developed duodenal cancer. The lifetime risk of developing this cancer by the age
      of 70 was 4% (95% confidence interval 1-7%) in the Dutch series and 3% (95%
      confidence interval 0-6%) in the Danish series. Decision analysis showed that
      surveillance led to an increase in life expectancy by seven months. CONCLUSIONS:
      Surveillance of the upper digestive tract led to a moderate gain in life
      expectancy. Future studies should evaluate whether this increase in life
      expectancy outweighs the morbidity of endoscopic examination and proximal
      pancreaticoduodenectomy.

PMID- 9245924
TI  - Reduction of non-steroidal anti-inflammatory drug induced gastric injury and
      leucocyte endothelial adhesion by octreotide.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers.
      AIMS: To assess whether the somatostatin analogue octreotide prevents NSAID
      induced mucosal gastrointestinal damage in both animals and humans. The effect of
      octreotide on neutrophil adhesion to the endothelium was also evaluated. METHODS:
      Male Sprague-Dawley rats were pretreated either with saline (0.3 ml
      subcutaneously) or octreotide (0.001-1 ng/kg subcutaneously). After 30 minutes
      gastric ulcers were induced by the intragastric application of NSAIDs (20 mg/kg
      indomethacin, 200 mg/kg aspirin, 200 mg/kg ibuprofen, or 50 mg/kg diclofenac).
      Four hours later the rats were killed and gastric mucosal lesions were assessed
      by computed planimetry. To determine whether octreotide could prevent
      indomethacin induced injury in humans, 20 healthy volunteers were evaluated in a
      double blind, placebo controlled study. RESULTS: Octreotide prevented NSAID
      induced gastric mucosal lesions (p < 0.05). The dose response curve was U shaped
      and the most effective dose was 0.1 ng/kg. Leucocyte adherence in submucosal
      venules of the stomach was evaluated by in vivo microscopy. Octreotide (0.1 ng/kg
      subcutaneously) prevented indomethacin (20 mg/kg intragastric) induced leucocyte
      adherence in gastric submucosal venules (p < 0.05). Healthy human volunteers
      received 50 mg indomethacin orally thrice a day concomitantly with either an
      identical placebo or 0.01 microgram, 0.1 microgram, or 1 microgram octreotide
      subcutaneously thrice a day for three days. Injury was assessed by endoscopy.
      There was a negative correlation between the octreotide dose and injury score (p
      < 0.03 for gastric injury, p < 0.001 for duodenal injury). CONCLUSIONS:
      Octreotide protects the stomach from NSAID induced gastric injury, probably via
      its ability to reduce NSAID induced neutrophilic adhesion to the
      microvasculature. Octreotide also ameliorated indomethacin induced gastric and
      duodenal injury in humans.

PMID- 9245925
TI  - Effects of Helicobacter pylori eradication therapy on hyperammonaemia in patients
      with liver cirrhosis.
AB  - BACKGROUND AND AIMS: Helicobacter pylori has strong urease activity. Ammonia
      produced by H pylori in the stomach can be a source of systemic ammonia in
      patients with hepatic dysfunction. The effect of the eradication of H pylori on
      hyperammonaemia was examined in patients with liver cirrhosis. SUBJECTS AND
      METHODS: Ammonia concentrations in blood and gastric juice were analysed in 50
      patients with liver cirrhosis and hyperammonaemia. All patients were first
      treated with a low protein diet, kanamycin, lactulose, and branched chain
      enriched amino acid solution. Hyperammonaemia remained in 18 patients. These 18
      patients were divided into three groups according to the status of H pylori
      infection; those with a diffuse distribution of H pylori in the stomach (group
      I), those with a regional distribution (group II), and those without H pylori
      (group III). These patients were given 30 mg iansoprazole, 1000 mg amoxicillin,
      and 400 mg clarithromycin or 500 mg metronidazole for two weeks to eradicate H
      pylori. RESULTS: In group I ammonia concentrations in blood and gastric juice
      were significantly reduced after H pylori eradication. The blood ammonia
      concentration at 12 weeks after the eradication was still significantly lower
      than that before eradication. In groups II and III the ammonia concentrations in
      blood and gastric juice were not significantly reduced after eradication therapy.
      CONCLUSIONS: The diffuse distribution of H-pylori in the stomach contributes
      partly to hyperammonaemia in patients with liver cirrhosis, and the eradication
      of H pylori is effective in patients with hyperammonaemia with diffuse H pylori
      infection in the stomach.

PMID- 9245926
TI  - In vitro evaluation of the role of antibodies against Helicobacter pylori in
      inhibiting adherence of the organism to gastric cells.
AB  - BACKGROUND: Once Helicobacter pylori infection is established, it is difficult to
      eradicate despite a persistent systemic and local immune response. It is not
      known whether immunisation can be used to prevent H pylori infection in humans.
      AIMS: To evaluate the effect of the human immune response on adherence of H
      pylori to gastric cells. METHODS: Human milk from a woman infected with H pylori
      and milk from a non-infected woman were each fractionated by chromatography on
      DEAE cellulose. Bacteria were incubated with either serum, human milk, human milk
      fractions, or secretory IgA before incubation with Kato III cells (cells from a
      gastric adenocarcinoma cell line). Bacterial adherence to the cells was assessed
      using flow cytometry. RESULTS: Serum from both the H pylori infected and non
      infected women killed H pylori. This resulted from the action of complement as
      heating the serum to 56 degrees C for 30 minutes abolished the bactericidal
      activity. Immunoglobulin fractions from serum of both infected and non-infected
      women did not inhibit H pylori adherence to Kato III cells. Human milk from the
      woman infected with H pylori and from the non-infected woman inhibited binding of
      H pylori to Kato III cells by 50 to 70%. Secretory IgA isolated from human milk
      had minimal inhibitory effect on adherence and this was notably less than the
      inhibitory effect of whole human milk. CONCLUSIONS: Human milk inhibits adherence
      of H pylori to Kato III cells and this inhibition is independent of whether or
      not the donor is infected with H pylori. Secretory IgA has minimal inhibitory
      effect on H pylori adherence.

PMID- 9245927
TI  - Gastric mucosal secretion of interleukin-10: relations to histopathology,
      Helicobacter pylori status, and tumour necrosis factor-alpha secretion.
AB  - BACKGROUND: Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti
      inflammatory and immunosuppressive properties. AIM: To determine whether this
      cytokine is involved in gastric mucosal inflammation in Helicobacter pylori
      infection. METHODS: The production of IL-10 by antral mucosal biopsy specimens
      during short term in vitro culture was determined by measuring IL-10 content of
      supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was
      determined by serology and histology, with gastritis scored using the Sydney
      system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also
      determined in a subgroup of patients. RESULTS: IL-10 secretion was significantly
      greater in patients with H pylori associated chronic gastritis than in patients
      who were H pylori negative with normal mucosa/reactive changes, and those with H
      pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a
      significant correlation overall between IL-10 secretion and chronic inflammation
      score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H
      pylori infected patients than uninfected patients with a normal mucosa (p <
      0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and
      0.38 respectively), but was only weakly correlated with IL-10 secretion (r =
      0.22, NS). CONCLUSIONS: Gastric mucosal production of IL-10 and TNF-alpha are
      increased in chronic gastritis associated with H pylori infection, and mucosal
      cytokine secretion varies with important histopathological aspects of gastric
      inflammation. Whereas the secretion of IL-10 in H pylori infection may be
      protective, limiting tissue damage caused by inflammation, it may also contribute
      towards failure of the immune response to eliminate the organism.

PMID- 9245928
TI  - Colonoscopic allergen provocation (COLAP): a new diagnostic approach for
      gastrointestinal food allergy.
AB  - BACKGROUND: The clinical relevance of gastrointestinal food allergy in adults is
      largely unknown because the mechanisms are poorly understood and the diagnosis is
      difficult to confirm. AIMS: To improve the diagnostic means for confirming
      intestinal food allergy on an objective basis, a new colonoscopic allergen
      provocation (COLAP) test was developed. PATIENTS: The COLAP test was performed in
      70 adult patients with abdominal symptoms suspected to be related to food
      allergy, and in five healthy volunteers. METHODS: During the COLAP test, the
      caecal mucosa was challenged endoscopically with three food antigen extracts, a
      buffer control, and a positive control (histamine). The mucosal weal and flare
      reaction was registered semiquantitatively 20 minutes after challenge, and tissue
      biopsy specimens were examined for mast cell and eosinophil activation. RESULTS:
      No severe systemic anaphylactic reactions were found in response to intestinal
      challenge. The COLAP test was positive to at least one food antigen in 54 of 70
      patients (77%), whereas no reaction in response to antigen was found in healthy
      volunteers. Antigen induced weal and flare reactions were correlated with
      intestinal mast cell and eosinophil activation, as well as with patients' history
      of adverse reactions to food, but not with serum concentrations of total or
      specific IgE or skin test results. CONCLUSION: The COLAP test may be a useful
      diagnostic measure in patients with suspected intestinal food allergy and may
      provide a new tool for the study of underlying mechanisms.

PMID- 9245929
TI  - Pre-illness dietary factors in inflammatory bowel disease.
AB  - BACKGROUND: The effect of environmental factors has been demonstrated in the
      pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them.
      AIM: To investigate the pre-illness diet in patients with recent IBD in
      comparison with matched population and clinic controls. METHODS: Quantified
      dietary histories were obtained from 87 patients with recent IBD (54 ulcerative
      colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for
      IBD were derived for intake levels of various foods. RESULTS: A high sucrose
      consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03)
      against population controls and 5.3 (p = 0.00) against clinic controls). Lactose
      consumption showed no effect while fructose intake was negatively associated with
      risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was
      associated with an increased risk for UC; this was particularly marked for animal
      fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of
      fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was
      negatively associated with the risk for IBD, while a positive association was
      found for retinol (p = 0.01). Most of the findings were similar in UC and CD
      except for potassium and vegetable consumption which showed a negative
      association only with risk for CD. CONCLUSIONS: An association was found between
      pre-illness diet and subsequent development of UC and CD. The effect of dietary
      components may be primary or modulatory.

PMID- 9245930
TI  - Renal tubular dysfunction in patients with inflammatory bowel disease treated
      with aminosalicylate.
AB  - BACKGROUND: An increasing number of case reports indicate potential
      nephrotoxicity of 5-aminosalicylic acid (5-ASA), which shares similarities with
      the chemical structures of both phenacetin and acetylsalicylic acid. AIM: In a
      point prevalence study the occurrence of sensitive indices indicative of early
      kidney malfunction was assessed in outpatients with inflammatory bowel disease.
      METHODS: Routine indices of kidney function (creatinine clearance, urinary
      protein content, pH, electrolytes, and microscopy) were investigated in 223
      patients with inflammatory bowel disease as well as sensitive markers of
      glomerular or tubular dysfunction (microproteinuria by SDS polyacrylamide gel
      electrophoresis (SDS-PAGE), urinary concentrations of N-acetyl-beta-D
      glucosaminidase, alpha 1-microglobulin, gamma-glutamyltransferase (GGT), alkaline
      phosphatase (AP), and albumin). Histories of exposure to 5-ASA were assessed by
      questionnaire. RESULTS: Patients receiving high amounts of 5-ASA, both actual as
      well as on a lifetime basis, showed an increased prevalence of tubular
      proteinuria by SDS-PAGE. Raised values for urinary AP and GGT indicate proximal
      tubular epithelial cells as the source. All other kidney function tests were
      normal. Analysis of covariates indicated strong associations between disease
      activity and size of 5-ASA doses as well as alterations in kidney tubular
      function. CONCLUSION: The possibility exists that high doses of 5-ASA may be
      associated with proximal tubular proteinuria. This point prevalence study cannot
      dissect the possible impact of chronic inflammation from high dose 5-ASA
      treatment and further prospective studies are warranted.

PMID- 9245931
TI  - Neurochemical coding in the small intestine of patients with Crohn's disease.
AB  - BACKGROUND: There have been conflicting results regarding the effect of Crohn's
      disease on the neurochemical composition of the enteric nervous system. AIMS: To
      examine the effect of Crohn's disease on the neurochemical composition of enteric
      nerve fibres and cell bodies using whole mount preparations of human ileum.
      METHODS: Whole wall ileum from seven normal subjects and nine patients with
      Crohn's disease was used to investigate the neurochemical composition of neurones
      and nerve fibres in the myenteric plexus, circular muscle, and serosa layer of
      ileum using immunohistochemical techniques. RESULTS: Increased tyrosine
      hydroxylase, 5-hydroxytryptamine, and neuropeptide Y immunoreactivity was
      exclusively seen in the myenteric plexus. There was increased neurofilament
      immunoreactivity in the myenteric plexus and nerve fibres of the circular muscle
      layer, and thick bundles of immunoreactive nerve fibres in the serosa layer.
      Increased vasoactive intestinal polypeptide, nitric oxide synthase, and pituitary
      adenylate cyclase activating peptide immunoreactivity was seen in the myenteric
      plexus and nerve fibres of the circular muscle layer, and aggregates of
      inflammatory cells in the serosa layer of the afflicted segment of Crohn's ileum.
      In addition, there was a chaotic display of nerve fibres containing some of the
      neuroactive substances with a high frequency of enlarged varicosities in the
      myenteric ganglia and/or nerve fibres of the circular muscle layer of Crohn's
      ileum. CONCLUSION: Results show quantitative as well as qualitative changes in
      the neurochemical composition of enteric nerve fibres and nerve cell bodies of
      Crohn's ileum. These changes and the presence of nitric oxide synthase and
      peptides immunoreactive inflammatory cells in the serosa layer suggest that nerve
      immune interactions may have a significant role in the process of the
      inflammatory changes seen in Crohn's ileitis.

PMID- 9245932
TI  - Rectal corticosteroids versus alternative treatments in ulcerative colitis: a
      meta-analysis.
AB  - BACKGROUND: Clear strategies to optimise the use of corticosteroids in ulcerative
      colitis are lacking. AIM: A meta-analysis was undertaken to examine critically
      the role of rectal corticosteroids in the management of active distal ulcerative
      colitis. METHODS: All reported randomised controlled trials were retrieved by
      searching the Medline and EMBASE databases and the bibliographies of relevant
      studies. Trials which met inclusion criteria were assessed for scientific rigour.
      Data were extracted by two independent observers according to predetermined
      criteria. RESULTS: Of 83 trials retrieved, 33 met inclusion criteria. Pooled odds
      ratios (POR) showed conventional rectal corticosteroids and rectal budesonide to
      be clearly superior to placebo. In seven trials, rectal 5-aminosalicylic acid (5
      ASA) was significantly better than conventional rectal corticosteroids for
      inducing remission of symptoms, endoscopy, and histology with POR of 2.42 (95%
      confidence interval (CI) 1.72-3.41), 1.89 (95% CI 1.29-2.76), and 2.03 (95% CI
      1.28-3.20), respectively. Rectal budesonide was of comparable efficacy to
      conventional corticosteroids but produced less endogenous cortisol suppression.
      Side effects, although inconsistently reported, were generally minor. A cost
      comparison of rectal preparations showed 5-ASA to be less expensive than
      corticosteroids. CONCLUSIONS: Rectal 5-ASA is superior to rectal corticosteroids
      in the management of distal ulcerative colitis.

PMID- 9245933
TI  - Histochemistry of the surface mucous gel layer of the human colon.
AB  - BACKGROUND AND AIMS: Histochemical analysis of the surface mucous gel layer of
      the human colon is difficult, as it dissolves in fixatives. This study was
      undertaken to explore the surface mucous gel layer on the normal mucosa and
      neoplastic tissues of the large intestine. In addition, the distribution of
      different mucins secreted from goblet cells was studied with a series of
      histochemical stains for mucins. METHODS: Twenty four surgically resected
      specimens were fixed in Carnoy's solution and embedded in paraffin. In four
      cases, the surface mucous gel layer was also studied in frozen sections. Serial
      sections were stained by a battery of histochemical techniques characterising
      mucins. RESULTS AND CONCLUSION: The surface mucous gel layer consisted of the
      inner and outer layers. The first covered the luminal surface of the mucosa,
      consisted of mucins, and showed a vertical striped pattern. The second overlaid
      the first, showed a lateral striped pattern, and was contaminated with bacteria
      and other substances. Their thickness in paraffin sections varied considerably
      among the sites in the large intestine, but was the thickest in the rectum and
      measured 12.7 (SEM 6.0) microns and 88.8 (SEM 80.1) microns respectively. Mucins
      forming the inner layer were obviously derived from goblet cells underlying it.

PMID- 9245934
TI  - Contribution of gastrointestinal transit and pouch characteristics in determining
      pouch function.
AB  - AIM: To determine the contributions of gastrointestinal transit and pouch
      characteristics to bowel frequency in patients with an ileoanal reservoir and no
      pouchitis. METHODS: Twenty one patients who had undergone restorative
      proctocolectomy, with ileostomy closure at least eight months previously, and who
      had no history of pouchitis were recruited. They were prospectively classified on
      the basis of their bowel frequency: 11 patients had good pouch function (bowel
      frequency less than six per day) and 10 had poor function (bowel frequency more
      than six per day). Gastrointestinal transit was studied using a dual isotope
      technique and anal and pouch physiological examination was performed on all
      patients. RESULTS: Lag phase, 25% and 50% gastric emptying, small bowel transit
      time, and 10% and 50% pouch filling times, all for solids and liquids, were not
      significantly different between patients with good and poor function. Anal
      manometry and pouch and anal electrical sensitivity were also similar in the two
      groups. The volume of air and water required to elicit an initial sensation and
      the urge to defaecate were similar in both groups, but the maximum tolerated
      volume to both air (525 v 245 ml, good v poor function, median values) and water
      (625 v 370 ml) infusion was significantly (both p < 0.02) lower in patients with
      poor function. CONCLUSION: Maximum tolerated volume in the pouch, which may
      reflect pouch size, sensitivity, compliance, or a combination of these is the
      major determinant of pouch function. Gastrointestinal transit does not seem to be
      an important determinant of function.

PMID- 9245935
TI  - Activation of cellular immune response in acute pancreatitis.
AB  - BACKGROUND: Inflammatory mediators have recently been implicated as potential
      markers of severity in acute pancreatitis. AIMS: To determine the value of
      neopterin and polymorphonuclear (PMN) elastase as markers of activation of
      cellular immunity and as early predictors of disease severity. PATIENTS: Fifty
      two non-consecutive patients classified according to their clinical outcome into
      mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and
      the PMN elastase/A1PI complex in plasma were measured during the first three days
      of hospital stay. RESULTS: Within three days after the onset of acute
      pancreatitis, PMN elastase was significantly higher in the severe pancreatitis
      group. Patients with severe disease also showed significantly higher values of
      neopterin on days 1 and 2 but not on day 3 compared with patients with mild
      disease. There was a significant correlation between PMN elastase and neopterin
      values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a
      sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN
      elastase in the probability of predicting disease severity. CONCLUSIONS: These
      data show that activation of cellular immunity is implicated in the pathogenesis
      of acute pancreatitis and may be a main contributory factor to disease severity.
      Neopterin was not superior to PMN elastase in the prediction of severity.

PMID- 9245936
TI  - Prevalence of the factor V Leiden mutation in hepatic and portal vein thrombosis.
AB  - BACKGROUND: The factor V Leiden (FVL) mutation has been shown to be the most
      frequent cause of hereditary thrombophilia. The prevalence of the mutation in
      patients with Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) has not
      been fully elucidated. AIMS: To investigate the association between the FVL
      mutation and BCS and PVT. PATIENTS: Thirty patients with BCS, 32 patients with
      PVT, and a control group of 54 patients with liver disorders and no history of
      thrombosis. METHODS: The factor V gene was analysed for the presence of the FVL
      mutation by a polymerase chain reaction (PCR) technique. The presence of the
      mutation was confirmed by DNA sequencing. RESULTS: Seven (23%) patients with BCS,
      one (3%) patient with PVT, and three (6%) patients in the control group were
      identified as having the FVL mutation. There of the BCS patients had coexisting
      hypercoagulable states. The prevalence of the FVL mutation was significantly
      higher in patients with BCS compared with patients with PVT and controls (p <
      0.04). The FVL mutation was the second most common aetiology associated with BCS.
      CONCLUSION: The FVL mutation is an important factor in the pathogenesis of BCS
      and screening for the disorder must be included in the investigation of patients
      presenting with this condition. In contrast, the FVL mutation is not a major
      predisposing factor in the pathogenesis of PVT.

PMID- 9245937
TI  - Enteropathy associated T cell lymphoma presenting as an isolated CNS lymphoma
      three years after diagnosis of coeliac disease: T cell receptor polymerase chain
      reaction studies failed to show the original enteropathy to be a clonal disorder.
AB  - A case of enteropathy associated T cell lymphoma is reported in a 45 year old
      woman, presenting with isolated disease in the CNS, three years after diagnosis
      of coeliac disease. Initial staging showed no evidence of gastrointestinal tract
      lymphoma. A presumptive diagnosis of T cell primary cerebral lymphoma was made
      and the patient was treated with combination chemotherapy and craniospinal
      radiotherapy. The patient relapsed, seven months after treatment, with small
      bowel lymphoma. The immunophenotype and T cell receptor polymerase chain reaction
      analysis confirmed the same tumour as in the CNS. Retrospective polymerase chain
      reaction analysis of intraepithelial lymphocytes in the duodenal biopsy sample,
      taken at the time of diagnosis of coeliac disease, failed to show evidence of a
      clonal T cell proliferation.

PMID- 9245938
TI  - Short answer in short segment Barrett's oesophagus.

PMID- 9245939
TI  - Helicobacter pylori, ammonia and the brain.

PMID- 9245940
TI  - Colonic mucus and ulcerative colitis.

PMID- 9245941
TI  - Biological monitoring: state of the art.

PMID- 9245942
TI  - Health and safety problems associated with long working hours: a review of the
      current position.
AB  - The European Community Directive on Working Time, which should have been
      implemented in member states of the European Community by November 1996, contains
      several requirements related to working hours, including the right of employees
      to refuse to work more than 48 hours a week. The United Kingdom government
      attempted to oppose the Directive, arguing that there is no convincing evidence
      that hours of work should be limited on health and safety grounds. Much of the
      research in this area has focused on the problems of shiftworking and previous
      reviews have therefore tended to emphasise this aspect of working hours. However,
      there is much less information about the effects of overtime work, which is a
      central element of the terms of the Directive. This paper reviews the current
      evidence relating to the potential effects on health and performance of
      extensions to the normal working day. Several gaps in the literature are
      identified. Research to date has been restricted to a limited range of health
      outcomes--namely, mental health and cardiovascular disorders. Other potential
      effects which are normally associated with stress--for example, gastrointestinal
      disorders, musculoskeletal disorders, and problems associated with depression of
      the immune system, have received little attention. Also, there have been few
      systematic investigations of performance effects, and little consideration of the
      implications for occupational exposure limits of extensions to the working day.
      Existing data relate largely to situations where working hours exceed 50 a week
      and there is a lack of information on hours below this level, which is of direct
      relevance to the European Community proposal. Finally, it is clear from
      investigations relating to shiftwork that a range of modifying factors are likely
      to influence the level and nature of health and performance outcomes. These
      include the attitudes and motivation of the people concerned, the job
      requirements, and other aspects of the organisational and cultural climate. It is
      concluded that there is currently sufficient evidence to raise concerns about the
      risks to health and safety of long working hours. However, much more work is
      required to define the level and nature of those risks.

PMID- 9245943
TI  - Pulmonary toxicity of components of textile paint linked to the Ardystil
      syndrome: intratracheal administration in hamsters.
AB  - OBJECTIVES: It was hypothesised from an epidemiological investigation that a
      formula change from Acramin FWR (a polyurea) to Acramin FWN (a polyamide-amine)
      had led to severe pulmonary disease in textile printing sprayers in SPAIN AND
      ALGERIA. To verify this, the pulmonary toxicity of the components of the paint
      systems involved was assessed in experimental animals. METHODS: Individual
      components and relevant mixtures, diluted in phosphate buttered saline, were
      given by intratracheal instillation of 2 ml/kg to hamsters. Pulmonary toxicity
      was assessed on days 3, 7, 14, 28, and 92 after a single intratracheal
      instillation, by histology and by measuring wet and dry lung weight, protein
      concentration, the activities of lactate dehydrogenase, alkaline phosphatase,
      beta-N-acetyl-glucosaminidase, and gamma-glutamyltransferase, inflammatory cell
      number and distribution in bronchoalveolar lavage fluid (BALF), and
      hydroxyproline content in dried lung tissue. RESULTS: Based on the doses that
      killed 50% of the animals (LD50s), the various components were found to be 10 to
      1250 times more toxic when given intratracheally than when given orally
      (according to reported oral LD50s in rats). Acramin FWN, Acramin FWR, Acrafix
      FHN, or their mixtures caused lung damage. Protein concentration, enzyme
      activities, total cell number, and percentage of polymorphonuclear neutrophils
      were increased in BALF during the first week after intratracheal instillation.
      Lung weights remained high for at least a month. Histology showed inflammatory
      cell infiltration and subsequent fibrosis with collagen deposition. This finding
      was confirmed by an increased hydroxyproline content in dried lung tissue.
      Acramoll W did not show toxic effects. CONCLUSIONS: The study suggests that there
      is no major difference, in hamsters, between the acute intratracheal toxicity of
      Acramin FWR and that of Acramin FWN. Consequently, there is no simple
      toxicological explanation for the epidemiological hypothesis. However, the
      pulmonary toxicity of these non-irritant polymeric compounds is surprisingly
      high. The Ardystil disaster and these results should serve as a strong warning
      that conventional toxicity testing of chemicals does not necessarily protect
      workers against respiratory toxicity.

PMID- 9245944
TI  - Mortality of doctors in different specialties: findings from a cohort of 20000
      NHS hospital consultants.
AB  - OBJECTIVES: To examine patterns of cause specific mortality in NHS hospital
      consultants according to their specialty and to assess these in the context of
      potential occupational exposures. METHODS: A historical cohort assembled from
      Department of Health records with follow up through the NHS Central Register
      involving 18,358 male and 2168 female NHS hospital consultants employed in
      England and Wales between 1962 and 1979. Main outcome measures examined were
      cause specific mortality during 1962-92 in all consultants combined, and
      separately for 17 specialty groups, with age, sex, and calendar year adjusted
      standardised mortality ratios (SMRs) for comparison with national rates, and rate
      ratios (RRs) for comparison with rates in all consultants combined. RESULTS: The
      2798 deaths at ages 25 to 74 reported during the 30 year study period were less
      than half the number expected on the basis of national rates (SMR 48, 95%
      confidence interval (95% CI) 46 to 49). Low mortality was evident for
      cardiovascular disease, lung cancer, other diseases related to smoking, and
      particularly for diabetes (SMR 14, 95% CI 6 to 29). Death rates from accidental
      poisoning were significantly raised among male consultants (SMR 227, 95% CI 135
      to 359), the excess being most apparent in obstetricians and gynaecologists (SMR
      934); almost all deaths from accidental poisoning involved prescription drugs. A
      significantly raised death rate from injury and poisoning among female
      consultants was due largely to a twofold excess of suicide (SMR 215, 95% CI 93 to
      423), the rate for this cause being significantly raised in anaesthetists (SMR
      405). Compared with all consultants, significantly raised mortality was found in
      psychiatrists for all causes combined (RR 1.12), ischaemic heart disease (RR
      1.18), and injury and poisoning (RR 1.46); in anaesthetists for cirrhosis (RR
      2.22); and in radiologists and radiotherapists for respiratory disease (RR 1.68).
      There were significant excesses of colon cancer in psychiatrists (RR 1.67,
      compared with all consultants) and ear, nose, and throat surgeons (RR 2.25);
      melanoma in anaesthetists (RR 3.33); bladder cancer in general surgeons (RR
      2.40); and laryngeal cancer in ophthalmologists (RR 7.63). CONCLUSIONS: Lower
      rates of smoking will have contributed substantially to the low overall death
      rates found in consultants, but other beneficial health related behaviours, and
      better access to health care, may have also played a part. The increased risks of
      accidental poisoning in male consultants, and of suicide in female consultants
      are of concern, and better preventive measures are needed. The few significant
      excesses of specific cancers found in certain specialties have no obvious
      explanation other than chance. A significant excess mortality from cirrhosis in
      anaesthetists might reflect an occupational hazard and may warrant further
      investigation.

PMID- 9245945
TI  - Lung cancer in relation to employment in the electrical utility industry and
      exposure to magnetic fields.
AB  - OBJECTIVES: A recent study found that lung cancer may be associated with
      exposures encountered in the electrical utility industry. To further evaluate
      this possibility, data were collected and analysed from five large electrical
      utility companies in the United States. METHODS: A cohort of 138905 male workers
      employed between 1950 and 1986 was followed up for mortality to the end of 1988,
      with 20733 deaths identified of which 1692 were due to lung cancer. Mortality
      from lung cancer was examined in relation to the duration of employment in
      specific jobs thought to have high exposure to 60 Hz magnetic fields and to an
      index of cumulative exposure to magnetic fields based on personal measurements.
      Exposure to pulsed electromagnetic fields (PEMFs) as estimated from another study
      was also considered. Poisson regression generated rate ratios for categories of
      exposure based on comparisons within the cohort adjusted for age, calendar year,
      race, socioeconomic status, work status, and estimated exposure to asbestos.
      RESULTS: Mortality rose modestly with duration of work as an electrician or power
      plant operator reaching rate ratios of 1.4 with > or = 20 years in those jobs but
      not with duration of work as a lineman or a combination of jobs thought to have
      high exposures to 60 Hz magnetic fields or PEMFs. Cumulative indices of exposure
      to 60 Hz magnetic fields and PEMFs were both associated with rate ratios of 1.2
      1.3 in the highest intervals. CONCLUSIONS: These data suggest that lung cancer is
      not strongly associated with duration of employment in specific jobs associated
      with high potential exposure to 60 Hz magnetic fields or to PEMFs. Small
      associations of lung cancer with indices of both 60 Hz magnetic fields and PEMFs
      leave open the possibility that larger associations have been diluted through
      exposure misclassification. Refined exposure assessment, especially to PEMFs,
      would be required to evaluate that possibility.

PMID- 9245946
TI  - Routes of asbestos exposure and the development of mesothelioma in an English
      region.
AB  - OBJECTIVES: To investigate the contribution of exposure to asbestos through
      different routes in the development of mesothelioma. METHODS: Case-control study.
      185 confirmed cases of mesothelioma and 160 controls were identified, when death
      had occurred between 1979 and 1991 in four health districts in Yorkshire. The
      surviving relatives were interviewed to ascertain lifetime exposure to asbestos.
      Adjusted odds ratios (ORs) of exposure to asbestos (through occupational,
      paraoccupational, and residential routes) were calculated for cases and were
      compared with controls. RESULTS: Likely or possible occupational exposure to
      asbestos was more common in cases than in controls (OR 5.6, 95% confidence
      interval (95% CI) 3.1 to 10.1). After excluding those with likely or possible
      occupational exposure, likely or possible paraoccupational exposure was more
      common in cases than controls (OR 5.8, 95% CI 1.8 to 19.2). Only six cases of
      mesothelioma were identified as being solely exposed to asbestos through their
      residence, compared with nine controls. The OR for residential exposure to
      asbestos varied between 1.5 and 6.6, depending on which potential industrial
      sources were included, but the 95% CIs were so wide that slightly reduced or
      greatly increased odds comparing cases with controls could not be excluded.
      CONCLUSION: Study results support previous evidence that occupational and
      paraoccupational exposure to asbestos is associated with developing mesothelioma.
      Despite a rigorous search, purely residential exposure seemed to account for only
      3% of identified cases. No firm conclusion can be drawn about the risks from
      residential exposure alone, as many of the study subjects could also have been
      occupationally or paraoccupationally exposed to asbestos.

PMID- 9245947
TI  - Progression of pleural and parenchymal disease on chest radiographs of workers
      exposed to amosite asbestos.
AB  - OBJECTIVES: To determine predictors of progression of pleural and parenchymal
      disease on the chest radiographs of workers exposed to a short term, intense
      exposure of amosite asbestos. METHODS: The first and last of a series of chest
      radiographs of 887 workers exposed to amosite was interpreted and coded according
      to International Labour Organisation (ILO) standards by two physicians.
      Significant predictors of disease progression were found by a linear stepwise
      regression analysis from among such variables as smoking history, latency (time
      since first exposure), duration and intensity of exposure, and cytology. RESULTS:
      Although most radiographs remained normal, some showed progression of disease
      with about twice as many patients with abnormalities on the last film. Various
      combinations of age, intensity of exposure, and time between films were
      significant predictors of pleural and parenchymal disease and progression of such
      disease. No predominance of one sided disease was noted. Cytology and smoking
      were unreliable predictors of disease. Most disease progression was minor,
      usually of less than two scoring categories. CONCLUSION: An intense, yet short,
      exposure to amosite asbestos can produce pleural and parenchymal changes on chest
      radiographs. The number of those affected roughly doubled over a period spanning
      10 to 20 years after exposure. Age and intensity of exposure are the most
      important predictors of disease.

PMID- 9245948
TI  - Respiratory health effects of opencast coalmining: a cross sectional study of
      current workers.
AB  - OBJECTIVE: To identify whether there is evidence of pneumoconiosis and other
      respiratory health effects associated with exposure to respirable mixed dust and
      quartz in United Kingdom opencast coalmines. METHODS: A cross sectional study of
      current workers (1224 men, 25 women) was carried out at nine large and medium
      sized opencast sites in England, Scotland, and Wales. To characterise a range of
      occupational groups within the industry, full shift measurements of personal
      exposures to respirable dust and quartz were taken. Up to three surveys were
      carried out at each site, covering all four seasons. For the purposes of
      comparisons with health indices these groups were further condensed into five
      broad combined occupational groups. Full sized chest radiographs, respiratory
      symptoms, occupational history questionnaires, and simple spirometry were used to
      characterise the respiratory health of the workforce. Logistic or multiple
      regression techniques were used to examine relations between indices of exposure
      and respiratory health. RESULTS: None of the group geometric mean dust
      concentrations, based on 626 valid dust samples, exceeded 1 mg.m-3, and 99% of
      all quartz concentrations were below 0.4 mg.m-3, the current maximum exposure
      limit. The highest quartz concentrations were experienced by the rock drilling
      team and drivers of bulldozers (used to move earth and stone from layers of
      coal). There were clear differences in mean respirable dust and quartz
      concentrations between occupational groups. These were consistent across the
      different sites, but depended in part on the day of measurement. The variations
      between sites were not much greater than between days, suggesting that
      differences between sites were at least partly explained by differences in
      conditions at the time of the measurements. The prevalence of radiographic small
      opacities profusion category > or = 1/0, based on the median of three readings,
      was 4.4%. Five men had category 2 pneumoconiosis and two men (including one of
      these five) had progressive massive fibrosis category A. From regression
      analyses, the relative risk of attaining a profusion of category > or = 0/1 was
      estimated to be doubled for every 10 years worked in the dustiest, preproduction
      opencast jobs, after allowing for age, smoking, and site effects. Risk was not
      associated with time worked in any other occupation within the industry, nor with
      previous employment in underground mining or other dusty jobs. Symptoms of
      chronic bronchitis were present in 13% of the men. Frequency of chronic
      bronchitis was influenced by years worked in dusty jobs outside opencast mining,
      but not by time spent in occupations within the industry. Asthmatic symptoms were
      reported by 5% of the workforce, close to the mean frequency found in adult men.
      No positive associations were found between asthma and occupational exposures.
      Lung function on average was close to predicted value and showed no relation to
      time worked in opencast occupations. CONCLUSIONS: Frequency of (mostly mild)
      chest radiographic abnormalities is associated with working in the dustier,
      preproduction jobs in the industry. Although some of these mild abnormalities may
      be non-occupational (due to aging or smoking), the association with exposure
      indicates a small risk of pneumoconiosis in these men, and the need to monitor
      and control exposures, particularly in the high risk occupations.

PMID- 9245949
TI  - In vivo analysis of cadmium in battery workers versus measurements of blood,
      urine, and workplace air.
AB  - OBJECTIVES: To measure in vivo the cadmium concentrations in kidney cortex
      (kidney-Cd) and in superficial liver tissue (liver-Cd) of nickel cadmium battery
      workers, and to compare the results with other commonly used estimates of cadmium
      exposure (current concentrations of cadmium in blood (B-Cd) and urine (U-Cd)) or
      repeated measurements of cadmium in workplace air (CumAir-Cd). METHODS: The study
      comprised 30 workers with a range of duration of exposure of 11-51 years. 13
      subjects were currently employed, whereas the other 17 had a median period
      without occupational exposure of eight years before the measurements. The in vivo
      measurements were made with an x ray fluorescence technique permitting average
      detection limits of 30 and 3 micrograms cadmium per g tissue in kidney and liver,
      respectively. RESULTS: 19 of 30 (63%) people had kidney-Cd and 13 of 27 (48%) had
      liver-Cd above the detection limits. Kidney-Cd ranged from non-detectable to 350
      micrograms/g and liver-Cd from non-detectable to 80 micrograms/g. The median
      kidney-Cd and liver-Cd were 55 micrograms/g and 3 micrograms/g, respectively.
      Kidney-Cd correlated significantly with B-Cd (r, 0.49) and U-Cd (r, 0.70),
      whereas liver-Cd correlated significantly with U-Cd (r, 0.58). Neither kidney-Cd
      nor liver-Cd correlated with the CumAir-Cd. The prevalence of beta 2
      microglobulinurea increased with increased liver-Cd. CONCLUSIONS: Current U-Cd
      can be used to predict the kidney-Cd and liver-Cd measured in vivo. In vivo
      measurements of kidney-Cd and liver-Cd were not shown to correlate with the
      individual cadmium exposure estimates, obtained by integration of the cadmium
      concentration in workplace air. There may be several reasons for this, including
      uncertainties in the estimate of the individual cumulative exposures as well as
      in the in vivo measurements. There was a suggestion of a relation between liver
      Cd and tubular proteinuria.

PMID- 9245950
TI  - Urinary neutral endopeptidase in workers exposed to cadmium: interaction with
      cigarette smoking.
AB  - OBJECTIVES: Structural impairment of the renal proximal tubular epithelium
      induced by cadmium (Cd) was investigated by measuring the concentration of
      neutral endopeptidase 24.11 (NEP), an ectoenzyme of the apical brush border, in
      the urine of 106 male workers employed in a Cd smelter (among whom 52 were
      occupationally exposed to Cd), and by comparing it with other tubular markers
      (low molecular weight proteins, lysosomal enzymes). METHODS: NEP (EC 3.4.24.11),
      beta-N-acetyl-glucosaminidase (NAG) (EC 3.2.1.30), and NAG-B isoenzyme activities
      were measured by fluorimetric assays, whereas the concentrations of retinol
      binding protein (RBP), beta 2-microglobulin (beta 2M), and Clara cell protein
      (CC16) were measured by automated latex agglutination techniques. RESULTS: An
      increased urinary excretion of NEP as well as microproteins was found only in
      subjects excreting more than 5 micrograms Cd/g creatinine. In this group, NEP
      concentrations were significantly higher in the subjects who smoked. This
      significant interaction could not be found for any other marker tested.
      CONCLUSIONS: The data suggest that NEP enzymuria is high even at low exposures to
      Cd (with a threshold of urinary cadmium excretion (U-Cd) at 5 micrograms/g
      creatinine), indicating early structural alterations. Moreover, its particular
      sensitivity to smoking could be useful in the detection of new population
      clusters potentially more susceptible to development of nephrotoxic insult.

PMID- 9245951
TI  - Minimal immunological effects on workers with prolonged low exposure to inorganic
      mercury.
AB  - OBJECTIVES: This study was carried out to investigate possible immunological
      changes in workers with prolonged low exposure to inorganic mercury in a
      fluorescent light bulb factory. METHODS: 29 immunological variables were examined
      in 34 workers with prolonged low level exposure to inorganic mercury (exposed
      workers) and 35 unexposed workers as the controls. The selected indicator of
      mercury exposure was concentration of mercury in the urine (U-Hg), which declined
      progressively from 36.0 micrograms/l in 1978 to 6.0 micrograms/l in the study
      year 1994. RESULTS: None of the exposed workers had ever shown signs of either
      acute or chronic inorganic mercury toxicity or had shown any form of
      hypersensitivity. The only changes found in the exposed workers, compared with
      the controls, were a reduction of the cells that express cluster differentiation
      (CD25,(T activation antigen (Tac antigen))) and concentrations of tumour necrosis
      factor-alpha (TNF-alpha) in serum. However, the decrease of cells that express
      CD25 was unrelated to occupational exposure and was, in all likelihood a chance
      finding. Conversely, the decline in serum TNF-alpha was closely associated with
      occupational exposure. However, no dose-response relation was found between U-Hg
      and TNF-alpha concentrations; nor were TNF-alpha concentrations affected by
      cumulative occupational exposure to inorganic mercury in over 20 years.
      CONCLUSIONS: Tentatively, we suggest that reduced serum TNF-alpha concentrations
      might be indicative of an in vivo functional defect of the monocyte macrophage
      system in this particular group of workers even though they were clinically
      asymptomatic.

PMID- 9245952
TI  - Surveillance of nasal and bladder cancer to locate sources of exposure to
      occupational carcinogens.
AB  - OBJECTIVE: To locate sources of occupational exposure to nasal and bladder
      carcinogens for surveillance follow up in British Columbia, Canada. METHODS:
      Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population
      based controls (n = 159) matched for sex and age, were interviewed about their
      jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57
      occupational groups with stratified exact methods to control for age, sex, and
      smoking. RESULTS: Occupational groups at increased risk of nasal cancer included:
      textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases,
      OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR
      3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not
      increased in occupations exposed to wood dust, possibly due to low exposures in
      local wood industries. Strongly increased risks of bladder cancer were found for
      sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners
      (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations
      originally considered at risk, the following had increased risks of bladder
      cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3);
      chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR
      1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups
      with increased risks and three or more cases with similar duties were selected
      for surveillance follow up. For nasal cancer, these included textile workers
      (five were garment makers) and pulp and paper workers (three performed
      maintenance tasks likely to entail stainless steel welding). For bladder cancer,
      these included miners (12 worked underground), machinists (five worked in
      traditional machining), hairdressers (three had applied hair dyes), and laundry
      workers (three were drycleaners).

PMID- 9245953
TI  - Self reported respiratory symptoms and diseases among hairdressers.
AB  - OBJECTIVES: Hairdressers are exposed to many irritative and allergenic substances
      capable of causing occupational respiratory symptoms and diseases. The self
      reported prevalence of respiratory symptoms and diseases was studied, and the
      risks among hairdressers compared with saleswomen was estimated. METHODS: A cross
      sectional prevalence study of respiratory symptoms and diseases was carried out
      among hairdressers and supermarket saleswomen, with a computer assisted telephone
      interview method (CATI). The study population comprised all the female
      hairdressers and supermarket saleswomen aged 15-54 years in the Helsinki
      metropolitan area, Finland. Disproportionate random samples of female
      hairdressers and sales-women were drawn from the trade union membership
      registers. The interviews were carried out between February and April 1994. A
      response rate of 80.5% (355/440) was obtained for hairdressers and 82.2%
      (583/709) for saleswomen. Atopy, smoking, chronic illnesses, type of work,
      working hours, working conditions, personal and professional use of hair
      products, and the use of personal protective devices were assessed. The outcome
      variables were self reported symptoms of the upper and lower respiratory tract.
      These were used to define chronic bronchitis, and asthma, laryngitis, and
      allergic rhinitis diagnosed by a physician. RESULTS: There was a considerable
      difference in the prevalence of chronic bronchitis; 6.8% in hairdressers versus
      1.9% in saleswomen. The odds ratio (OR) adjusted for age, smoking, and atopy for
      chronic bronchitis indicated an increased risk of chronic bronchitis (OR 4.8, 95%
      confidence interval (95% CI) 2.2 to 10.1). No association was found between work
      as a hairdresser and asthma, laryngitis, and allergic rhinitis. Also the
      prevalence of rhinitis, rhinitis with eye symptoms, cough with phlegm, dyspnoea,
      and dyspnoea accompanied by cough was increased among hairdressers. The
      corresponding adjusted risk ORs were 1.7 (95% CI 1.3 to 2.3) for rhinitis, 1.9
      (95% CI 1.4 to 2.6) for rhinitis with eye symptoms, 1.4 (CI 1.1 to 1.9) for cough
      with phlegm, 1.5 (95% CI 1.0 to 2.2) for dyspnoea, and 1.6 (95% CI 1.0 to 2.7)
      for dyspnoea with cough. CONCLUSIONS: Our results indicate an increased
      prevalence of upper and lower respiratory symptoms among hairdressers. Allergenic
      and irritative chemicals in hairdressing are likely candidates explaining the
      difference found between the hairdressers and controls. Work related reasons
      should be considered when a hairdresser presents with airway symptoms. Preventive
      actions are needed to improve the working conditions and personal protection.

PMID- 9245954
TI  - The need for effective contrast agents to enhance the performance of MR imaging.

PMID- 9245955
TI  - Liver imaging. Clinical applications and future perspectives.
AB  - Primary hepatocellular carcinoma and liver metastases affect several million
      people each year. The main imaging modalities to detect and assist diagnosis of
      primary and secondary liver tumours include MR imaging, CT, and US. The value of
      these techniques is further increased by the use of contrast agents which
      increase the sensitivity, and sometimes also the specificity, of the
      investigations. The relative advantages and drawbacks of the different contrast
      agents and imaging modalities in the detection and characterisation of liver
      tumours are discussed. Currently there is no consensus amongst investigators as
      to which is superior, due to the technical complexities and number of
      combinations possible within each of the different modalities. There continues to
      be advances in the hardware and software of imaging equipment, as well as a trend
      to develop new contrast agents with more organ-specificity. These include those
      targeting the hepatocytes, such as mangafodipir trisodium (MnDPDP, Teslascan),
      and those with reticuloendothelial cell specificity, such as the
      superparamagnetic iron oxides. These developments have the potential for making
      significant contributions to the diagnostic value of imaging procedures and, by
      reducing the number of investigations necessary to reach a final diagnosis,
      having a significant and beneficial impact on the pharmaco-economics of patient
      health care.

PMID- 9245956
TI  - MnDPDP for MR imaging of the liver. Results from the European phase III studies.
AB  - PURPOSE: To evaluate the diagnostic efficacy and safety of MnDPDP (Teslascan) in
      enhanced MR imaging. MATERIAL AND METHODS: In 2 multiple independent trials in
      Europe 624 patients were given MnDPDP intravenously at 5 mumol/kg b.w. Patients
      underwent an unenhanced MR examination comprising T1-weighted spin-echo and
      breath-hold gradient-echo sequences and a T2-weighted spin-echo sequence. The T1
      sequences were repeated after the administration of MnDPDP. In a subgroup of 137
      patients the results of the enhanced MR images were compared with the results of
      contrast-enhanced CT (CECT) images. RESULTS: For both types of T1-weighted
      sequences and when evaluating the maximum numbers of lesions seen in all imaging
      sequences, the total numbers of lesions seen were significantly higher in the
      MnDPDP-enhanced images than in the unenhanced images (p = 0.0005 and p = 0.0001,
      respectively). The investigators considered the enhanced images to contain "other
      additional information not found in the unenhanced images" in 279 (45%) of the
      621 patients examined. The MnDPDP-enhanced images were also superior to the CECT
      images in the detection of lesions (p = 0.02). Adverse events were reported by 46
      patients (7%) and infusion-associated discomfort by 26 (4%). Heart rates and
      systolic and diastolic blood pressures showed no clinically significant changes
      from baseline as a result of the administration of the contrast medium.
      CONCLUSION: MnDPDP was shown to be effective and safe in enhanced MR imaging of
      the liver.

PMID- 9245957
TI  - MnDPDP for MR imaging of the liver. Results of an independent image evaluation of
      the European phase III studies.
AB  - PURPOSE: To evaluate the diagnostic efficacy of mangafodipir trisodium (MnDPDP,
      Teslascan) as a new contrast agent for MR imaging of the liver based on an
      independent evaluation of the MR images from the European phase III studies.
      MATERIAL AND METHODS: MR imaging of the liver was done at 0.5-2.0 T in 17
      European centres and included T1-weighted spin-echo and gradient-echo sequences
      before and after administration of MnDPDP to patients at a dose of 5 mumol/kg
      b.w. T2-weighted images were also obtained in all cases before the i.v. injection
      of the agent. Images of a total of 592 patients were evaluated by 4 independent
      experienced radiologists who were not involved in the on-site clinical trials.
      RESULTS: Statistically significantly more lesions were detected (p = 0.0014) in
      MnDPDP-enhanced T1-weighted MR images than in unenhanced images. T1-weighted
      gradient-echo sequences were found to be superior to T1-weighted spin-echo
      sequences after injection of MnDPDP. The post-contrast images were found to be
      statistically significantly superior to the pre-contrast images in confidence in
      the presence of a lesion (p < or = 0.0001), quality of lesion delineation (p < or
      = 0.0001), lesion conspicuity (p < or = 0.0001) and in the confidence in the
      diagnosis of a lesion (p = 0.001). CONCLUSION: This independent evaluation of the
      European phase III trials confirmed the superiority of MnDPDP-enhanced MR images
      over unenhanced images for lesion detection and characterization.

PMID- 9245958
TI  - Diagnostic efficacy of MnDPDP in MR imaging of the liver. A phase III multicentre
      study.
AB  - PURPOSE: To assess the diagnostic efficacy, safety and tolerability of
      mangafodipir trisodium (MnDPDP, Teslascan) in MR imaging of the liver. MATERIAL
      AND METHODS: Eighty-two patients from 4 centres underwent MR imaging with pre
      contrast sequences including T1-weighted SE and GRE, and T2-weighted turbo SE
      sequences. MnDPDP at a dose of 5 mumol/kg b.w. was administered by slow i.v.
      infusion, and 20-60 min after infusion the T1-weighted SE and GRE sequences were
      repeated. Diagnostic efficacy was evaluated by counting the number of lesions and
      by evaluating whether more information for lesion characterisation was available
      in post-contrast images. Safety and tolerability were assessed by recording
      adverse events and infusion-related discomfort. RESULTS: Significantly more
      lesions were found in MnDPDP-enhanced T1-weighted SE and GRE images than in
      unenhanced images of the same sequences. More lesions were also found in these
      images compared with T2-weighted images at a level of marginal significance. More
      information was obtained from MnDPDP-enhanced images in 40 cases. Mild to
      moderate adverse events were experienced by 17% of the patients. CONCLUSION:
      MnDPDP-enhanced images can improve lesion detection in the liver and are helpful
      for lesion characterisation. To obtain optimal diagnostic information of liver
      lesions T2-weighted images are also valuable. MnDPDP is a safe contrast agent for
      MR imaging of liver lesions.

PMID- 9245959
TI  - MnDPDP-enhanced MR imaging of the liver. Correlation with surgical findings.
AB  - PURPOSE: To compare lesion detection and characterisation predicted by MnDPDP
      enhanced MR imaging with surgical excision and pathological examination. MATERIAL
      AND METHODS: Ninety patients were intravenously infused at a rate of 2 to 3
      ml/min with 5 mumol/kg mangafodipir trisodium (MnDPDP, Teslascan). The patients
      were examined with spin-echo and gradient-echo T1-weighted MR imaging at 1 h and
      24 h after the end of infusion. The results were compared with identical pre
      contrast sequences. In 20 of these patients, the pre-operative MR findings were
      compared with intra-operative ultrasonography and histology of the resected liver
      specimens. RESULTS: In those with liver metastases, there was a good correlation
      between MR and the hepatic disease in 11 out of 14 cases. In the group with
      primary liver tumours, MR findings correlated with hepatic disease in 5 out of 6
      cases. CONCLUSION: Liver lesion characterisation is possible with MnDPDP, and MR
      contrast enhancement with this agent is considered to be an important adjunct to
      the radiological assessment of patients with neoplastic liver disease where
      accurate decisions for surgical planning are imperative.

PMID- 9245961
TI  - Overview of MnDPDP as a pancreas-specific contrast agent for MR imaging.
AB  - PURPOSE: To describe and discuss previous and ongoing clinical and experimental
      studies with MnDPDP (Teslascan) as a pancreas-specific contrast agent for MR
      imaging. MATERIAL AND METHODS: All results, both experimental and clinical,
      applying MnDPDP as a pancreas-specific contrast agent for MR imaging, were
      collected. RESULTS: An increase of up to 100% in signal intensity was seen in
      normal pancreatic parenchyma, reaching its maximum approximately 25 min after the
      beginning of MnDPDP administration. Maximal enhancement was sustained for 4 h.
      Enhancement was only seen in the T1-weighted images. No enhancement was observed
      in tumours and an increase in contrast-to-noise of about 200% was obtained. The
      uptake of MnDPDP in pancreatitis compared with normal pancreatic parenchyma was
      decreased in an animal model. CONCLUSION: Improved depiction and demarcation of
      pancreatic tumours with MR imaging were obtained after administration of MnDPDP.
      MR imaging with and without MnDPDP might be valuable for staging of pancreatitis.

PMID- 9245960
TI  - Tumoural portal vein thrombosis. Enhancement with MnDPDP.
AB  - PURPOSE: Intrahepatic thrombus is usually associated with either cirrhosis or
      hepatocellular carcinoma (HCC). Most HCCs enhance after the administration of
      MnDPDP (Teslascan). Our objective was to analyze the enhancement characteristics
      of tumour portal vein thrombi. MATERIAL AND METHODS: Thrombi affecting the main
      or segmental portal veins (17 cases) and the suprahepatic inferior vena cava (1
      case) were retrospectively selected from a series of 128 patients studied with MR
      imaging before and after the administration of MnDPDP. Enhancement was assessed
      qualitatively and quantitatively. RESULTS: All tumour thrombi enhanced after
      MnDPDP administration. The enhancement was more conspicuous in the GRE images. On
      the quantitative evaluation, the portal thrombus enhancement was greater for GRE
      images than SE images. Portal thrombi enhanced more than the liver and the HCCs.
      There was a significant difference between the enhancement of the HCCs and the
      thrombi with both MR imaging techniques. CONCLUSION: The greater enhancement of
      the tumour thrombus associated with the liver and HCC may suggest that other
      mechanisms, apart from accumulation of the contrast medium within the hepatocytes
      inside the thrombi, are involved in thrombus enhancement.

PMID- 9245962
TI  - MR imaging properties and pharmacokinetics of MnDPDP in healthy volunteers.
AB  - PURPOSE: Thirteen male volunteers were studied to evaluate the MR imaging
      properties and pharmacokinetics of 10 mM mangafodipir trisodium infusion (MnDPDP,
      Teslascan). MATERIAL AND METHODS: Doses of 5 and 10 mumol/kg b.w. were
      administered by bolus injection (< 1 min) to 5 subjects, and by infusion (20 min)
      to 8 subjects, with a 3-week wash-out between doses. Infusion subjects underwent
      MR imaging. RESULTS: At 1 h after infusion, the plasma concentration of Mn was
      reduced to approximately 15% of the maximum value. Fifteen to 20% of Mn was
      recovered in the urine, and 50-60% was recovered in the faeces. The rapid initial
      plasma clearance of Mn is consistent with both rapid tissue uptake and rapid
      renal elimination. Increases in signal intensity were apparent on T1-weighted
      images of the liver, pancreas, spleen, renal cortex and the renal medulla, but
      not in regions of the brain protected by an intact blood-brain barrier. Increases
      were seen in the choroid plexus and pituitary. Contrast-related adverse events,
      only flushing of moderate intensity, occurred in bolus injection subjects.
      CONCLUSION: At 5 and 10 mumol/kg, mangafodipir produces relatively long-lasting
      enhancement of several abdominal organs, including the liver, pancreas and
      kidney.

PMID- 9245964
TI  - Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat
      and dog after intravenous administration.
AB  - PURPOSE: To investigate distribution and excretion of mangafodipir (MnDPDP,
      Teslascan) in the rat and dog. MATERIAL AND METHODS: Formulations of either 14C
      MnDPDP or 54MnDPDP were injected intravenously at near clinical doses in rats and
      dogs. RESULTS: The manganese (Mn) moiety is rapidly removed from plasma with an
      elimination half-life of less than 25 min in both species, reflecting a rapid
      distribution to the tissues and an early excretion. The plasma clearance of the
      DPDP moiety is slower than that of Mn and it appears to distribute into the
      extracellular fluid. Mn is distributed largely to the liver, pancreas and
      kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental
      passage of DPDP could be detected. The metal is mainly excreted by the faecal
      route, with a small fraction eliminated early in the urine. DPDP is rapidly and
      essentially completely excreted in the urine, consistent with the glomerular
      filtration rate. CONCLUSION: The ligand does not appear to facilitate the
      transport of Mn into any organ except the kidney for subsequent excretion, and it
      reduces distribution to the heart. The Mn is taken up by those organs indicated
      for MR imaging, primarily liver and pancreas.

PMID- 9245963
TI  - Metabolism and pharmacokinetics of MnDPDP in man.
AB  - PURPOSE: To study the metabolism and pharmacokinetics of mangafodipir trisodium
      injection, 0.01 mmol/ml (Teslascan), in healthy male volunteers. MATERIAL AND
      METHODS: Eight volunteers received mangafodipir trisodium as an infusion over 20
      min, and 5 received it as an injection (< 1 min). Both groups received 5 and 10
      mumol/kg b.w. with a wash-out period of 3 weeks between doses. Metabolites were
      measured in plasma, total manganese and zinc were measured in plasma and urine
      and total manganese was measured in faeces. RESULTS: The parent compound MnDPDP
      (manganese dipyridoxyl diphosphate) and 5 metabolites; MnDPMP (manganese
      dipyridoxyl monophosphate). MnPLED (manganese dipyridoxyl ethylenediamine) and
      the corresponding zinc compounds ZnDPDP, ZnDPMP and ZnPLED, were detected in
      plasma. ZnPLED was the only detectable metabolite 8 h after dosing. The apparent
      volume of distribution of manganese exceeded the interstitial body fluids. The
      volume of distribution of the ligand indicated distribution to the extracellular
      fluid only, with the plasma clearance close to the glomerular filtration rate.
      The manganese was incompletely excreted during the 4 days after treatment with
      the major part in faeces and less than 20% of the dose in the urine. CONCLUSION:
      Dephosphorylation and simultaneous transmetallation with zinc are the main
      metabolic pathways of MnDPDP in man.

PMID- 9245966
TI  - NMR relaxation studies with MnDPDP.
AB  - PURPOSE: Our studies were designed to compare the efficacy of mangafodipir
      trisodium (MnDPDP, Teslascan) as a tissue-specific MR agent with that of
      manganese chloride (MnCl2), to compare the efficacy of different doses and rates
      of administration of MnDPDP, and to collect the data needed for predicting
      optimum pulse sequences. MATERIAL AND METHODS: The dose response for the
      relaxation rates R1 and R2 at 0.47 T, and the manganese (Mn) concentrations in
      rat liver and in the liver, pancreas, heart and adrenals of pigs was determined
      for both MnDPDP and MnCl2 administered i.v. Computer simulations were carried out
      to model the effects of different tissue Mn concentrations and TR on signal
      intensities and contrast-to-noise ratios. RESULTS: In rat liver and pig organs
      both compounds produced a positive dose-response in R1 and tissue Mn
      concentration, and only small or no response in R2. The Mn concentration in rat
      liver was positively correlated with R1, regardless of the form in which Mn was
      given, or the rate of administration. Optimal imaging parameters are therefore
      expected to be different pre- and post-MnDPDP administration. CONCLUSION: The
      added cardiovascular safety of MnDPDP compared with MnCl2 does not result in loss
      of efficacy in increasing RI at the intended clinical dose of 5 mumol/kg MnDPDP.
      The changes in R2 were too small to affect T2-weighted images. The data give the
      basis for choosing the appropriate pulse sequences for MnDPDP-enhanced MR
      imaging.

PMID- 9245965
TI  - Comparison of manganese biodistribution and MR contrast enhancement in rats after
      intravenous injection of MnDPDP and MnCl2.
AB  - PURPOSE: To compare the time course of the MR enhancing properties and
      biodistribution of manganese (Mn) in rats given i.v. Mn dipyridoxyl diphosphate
      (MnDPDP) or Mn chloride (MnCl2). MATERIAL AND METHODS: Twenty-four adult rats
      were injected i.v. with 5 mumol/kg MnDPDP or MnCl2, or with 0.5 ml/kg saline.
      High resolution T1-weighted MR imaging was performed during early (10 min), mid
      (2 h) and late (24 h) phases after injection. Mn concentrations in major organs
      were measured by using an ICP-AES technique, and correlated with MR findings.
      RESULTS: Variable degrees of signal enhancement of major organs observed in MR
      images corresponded with the amount of Mn uptake after injection of MnDPDP or
      MnCl2. A prominently lower cardiac, pancreatic and hepatic uptake of Mn was seen
      at 10 min in rats injected with MnDPDP compared with those given MnCl2 and this
      was reflected in a difference in signal intensity (SI) in the MR images. At 2 h,
      the Mn content and SI in the major organs were similar with both MnDPDP and
      MnCl2. An overall Mn clearance was achieved at 24 h without any important organ
      retention, with kidney excretion of Mn seen only with MnDPDP. CONCLUSION: With
      both MnDPDP and MnCl2, the Mn uptake correlates with the SI enhancement in
      tissues. The reduced initial cardiac uptake of Mn after MnDPDP treatment compared
      to MnCl2 may account for the favourable cardiovascular safety of the contrast
      agent. These data contribute to an understanding of SI enhancement by MnDPDP, and
      are consistent with other studies showing that at a dose of 5 mumol/kg, MnDPDP
      can be safely used as a potent MR organ-specific contrast agent.

PMID- 9245967
TI  - MnDPDP enhancement in rabbit liver after intravenous bolus injection and slow
      infusion.
AB  - PURPOSE: To investigate the MR-enhancing effect of mangafodipir trisodium
      (MnDPDP, Teslascan) in the rabbit liver in relation to dose, mode of
      administration and imaging window. MATERIAL AND METHODS: MnDPDP was administered
      to 18 rabbits at a dose of 10 mumol/kg or 20 mumol/kg, as a bolus injection or
      infusion. MR imaging of the liver was performed at different time intervals.
      RESULTS: Peak liver enhancement was typically observed 10-30 min after
      administration and the enhancement declined with a half-time of about 5 h. This
      pattern was observed in all sequences (SE 400/15, FLASH, and SE 132/10), with
      both doses and with both rates of administration. The peak enhancement was
      greater, though not significantly so after 20 mumol/kg than after 10 mumol/kg. A
      higher relative peak signal was observed with SE 132/10 than with FLASH or SE
      400/15. CONCLUSION: A good liver imaging result was obtained after a dose of 10
      mumol/kg, either bolus or infusion, 10-30 min post-contrast with heavily T1
      weighted sequences.

PMID- 9245968
TI  - Clinical implications of studies with MnDPDP in animal models of hepatic
      abnormalities.
AB  - Mangafodipir trisodium (manganese dipyridoxal diphosphate or MnDPDP) has been
      introduced as a hepatobiliary MR contrast agent (Teslascan). Its potential to
      assist in the characterisation of focal liver lesions, the diagnosis of local and
      global obstructive cholestasis and the evaluation of hepatic function in diffuse
      liver diseases has been explored in multiple pre-clinical experiments with
      appropriate animal models. The prompt negative contrast enhancement and delayed
      peritumoural rim-enhancement seen after i.v. injection of MnDPDP are 2 typical
      features of primary and secondary liver tumours with high malignancy, while the
      persistent positive enhancement is a sign of liver tumours of well preserved
      hepatocytic nature. Liver with local and total biliary obstruction can be
      visualized in MnDPDP-enhanced MR images as a region with prolonged signal
      enhancement. This agent could also be used to non-invasively evaluate diffuse
      liver diseases of different causes. In the present paper, we review the
      experimental data in the literature, provide some unpublished results and discuss
      the potential impact on the clinical use of MnDPDP in the liver. We conclude that
      MnDPDP is a promising MR liver contrast agent for the detection and
      characterisation of focal and diffuse liver diseases.

PMID- 9245969
TI  - Tissue distribution and general safety of MnDPDP in male beagle dogs, with or
      without total common bile duct obstruction.
AB  - PURPOSE: Evaluation of the tissue distribution of manganese (Mn) and general
      safety in normal and cholestatic male beagle dogs after i.v. administration of
      mangafodipir trisodium (MnDPDP, Teslascan). MATERIAL AND METHODS: Male beagle
      dogs, with or without surgical obstruction of the common bile duct, received a
      single i.v. bolus injection of saline (control), or MnDPDP at doses of 10 or 50
      mumol/kg b.w. and were sacrificed 1 or 7 days after treatment. Toxicity was
      assessed and tissue concentrations of Mn were measured. RESULTS: Increased tissue
      Mn concentrations were found in all dogs treated with MnDPDP and were greatest in
      those with biliary obstruction. Although Mn concentrations decreased with time in
      most tissues in each of the treated groups, this was not the case for the brain
      and adrenal glands in dogs with total biliary obstruction in which further
      increases in Mn concentrations were seen at the later time point. This suggested
      a re-distribution of Mn from the major body depots such as the liver. There were
      no effects of MnDPDP on clinical signs/behaviour, organ weights, histomorphology
      or clinical biochemistry. CONCLUSION: These findings indicate that a single
      clinical dose of 5 mumol/kg MnDPDP is likely to be well tolerated in patients
      with cholestasis.

PMID- 9245970
TI  - Cardiovascular safety of MnDPDP and MnCl2.
AB  - PURPOSE: To investigate the apparent discrepancy between expected basic
      physiological responses at the cellular level and the in vivo behaviour of both
      MnDPDP and MnCl2 administered i.v. prompted parallel investigations of these
      substances. MATERIAL AND METHODS: Studies were performed in isolated perfused rat
      hearts, isolated bovine mesenteric arteries, conscious dogs, and dogs with acute
      ischaemic heart failure. RESULTS: These studies confirmed that Mn+2 at high
      concentrations acted as a calcium antagonist inducing negative inotropy. Mn+2 at
      low concentrations was an effective superoxide scavenger, conserving nitric oxide
      and facilitating vasodilation. Mn+2 maintained or elevated heart rate (HR) and
      blood pressure (BP), and did not worsen existing cardiac failure. MnDPDP was
      about 10 times less potent than MnCl2 in eliciting these cardiovascular
      responses. CONCLUSION: The ex vivo properties of Mn+2, inducing vasodilation and
      negative inotropy, are counter-balanced in vivo through the action of 2
      mechanisms: extensive plasma protein binding reducing active M+2, and the release
      of catecholamines which maintain or even raise HR and BP. Taken together with
      pharmacokinetic factors, including maximal plasma concentrations in humans given
      the recommended 5 mumol/kg dose, it is concluded that MnDPDP in normal clinical
      use represents no safety risk to the cardiovascular system.

PMID- 9245971
TI  - Cardiovascular effects of MnDPDP and MnCl2 in dogs with acute ischaemic heart
      failure.
AB  - PURPOSE: To examine the cardiovascular effects of MnDPDP in a model of acute
      heart failure in the dog, and to compare these effects with those of MnCl2.
      MATERIAL AND METHODS: The study involved slow i.v. infusion of either 10, 60 and
      300 mumol/kg of MnDPDP, or 1, 6 and 30 mumol/kg MnCl2, in increasing doses to
      groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of
      polystyrene microspheres (50 +/- 10 microns) into the left coronary artery until
      a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was
      achieved. The following test parameters were measured: left ventricular end
      diastolic pressure; the first derivatives of maximum rate of left ventricular
      contraction and relaxation; mean aortic pressure; pulmonary artery pressure;
      right atrial pressure; cardiac output; heart rate; QT-time; PQ-time; QRS-width;
      and plasma catecholamines. RESULTS: Slow infusion of MnDPDP at doses up to and
      including 12 times the clinical dose was well tolerated in dogs without further
      depression of cardiovascular function during acute ischaemic heart failure. At
      300 mumol/kg, i.e. 60 times the human dose, only minor haemodynamic and
      electrophysiological effects were seen, and these were similar to those seen
      after administration of 30 mumol/kg MnCl2. CONCLUSION: The present study suggests
      that slow infusion of MnDPDP should not cause further deterioration of cardiac
      function in patients with heart failure.

PMID- 9245972
TI  - The reproductive toxicology of intravenously administered MnDPDP in the rat and
      rabbit.
AB  - PURPOSE: The reproductive toxicology of mangafodipir trisodium (MnDPDP,
      Teslascan), a new hepatobiliary MR contrast agent, was evaluated in rats and
      rabbits. MATERIAL AND METHODS: Male and female fertility and post-natal
      development were examined in rats after repeated i.v. injections of MnDPDP. The
      developmental toxicity in rats was investigated after repeated daily i.v.
      injections during organogenesis with MnDPDP, MnCl2, or DPDP, as well as with
      MnCl2 administered orally. The developmental toxicity of i.v. injected MnDPDP was
      also investigated in rabbits. RESULTS: MnDPDP (100 mumol/kg) had no adverse
      effects on rat fertility. However, both MnDPDP (10-40 mumol/kg) and MnCl2 (30
      mumol/kg) caused skeletal abnormalities in the rat, but not in the rabbit given
      20 mumol MnDPDP/kg. Maternal treatment of rats with MnDPDP (40 mumol/kg) reduced
      survival and body weights of neonates, and adversely affected their functional,
      but not physical development. No skeletal abnormalities were seen in the rat
      after i.v. administered DPDP (40 mumol/kg) or MnCl2 (6 mumol/kg), or after MnCl2
      (400 mumol/kg) given by oral gavage. Maternal toxicity was not seen in rats or
      rabbits given these doses. CONCLUSION: MnDPDP caused skeletal abnormalities in
      foetal rats, but not rabbits, and had no effects on rat fertility. Manganese
      appears to be the causative agent for inducing bone abnormalities in the rat.

PMID- 9245973
TI  - General toxicology of MnDPDP.
AB  - PURPOSE: To investigate the general toxicology of mangafodipir trisodium (MnDPDP,
      Teslascan). MATERIAL AND METHODS: Studies were performed in accordance with
      standard methods and in compliance with regulations current at the time of
      conduct. RESULTS: Single-dose studies in rodents and dogs showed that MnDPDP was
      tolerated at doses of approximately 2000 mumol/kg, approximately 400 times a
      single imaging dose of 5 mumol/kg. The single dose tolerance of MnDPDP was
      approximately 10 times greater than MnCl2. A good safety profile of MnDPDP was
      also shown in repeat-dose studies (3 weeks), in which the no-observed-adverse
      effect level for the rat, monkey and dog was 116, 29 and 10 mumol/kg,
      respectively. The local tolerance studies indicated that no adverse local tissue
      reactions are likely to occur after i.v. injection. Other studies indicate that
      accidental spillage of MnDPDP onto the skin is not expected to lead to
      significant systemic exposure, or to local irritation or hypersensitivity. MnDPDP
      was not genotoxic in a battery of several different tests. CONCLUSION: MnDPDP was
      shown to have a good safety profile suitable as an hepatobiliary MR contrast
      agent for i.v. administration.

PMID- 9245974
TI  - Physicochemical characterisation of mangafodipir trisodium.
AB  - PURPOSE: To determine the structure and various physicochemical properties of
      mangafodipir (MnDPDP) trisodium, the active ingredient of Teslascan, a new-organ
      specific contrast medium for MR imaging. MATERIAL AND METHODS: The structure of
      MnDPDP trisodium crystals was determined by X-ray crystallography. The possible
      existence of polymorphism in MnDPDP trisodium was evaluated by powder X-ray
      diffraction, optical microscopy, thermal analysis and IR spectroscopy. In
      addition, various spectroscopic techniques and physicochemical measurements were
      used for characterisation of MnDPDP trisodium. RESULTS: The crystallographic data
      obtained for MnDPDP trisodium show that the general core structure of the MnDPDP
      anion is similar to that seen in related substances. The metal coordination
      geometry is a distorted octahedron defined by 2 phenolate oxygens, 2 carboxylate
      oxygens and 2 amine nitrogens. The unit cell contains 2 MnDPDP anions, 6 sodium
      ions and 50 water molecules. The various spectroscopic data are consistent with
      the structure determined by X-ray crystallography. The product (Teslascan) has
      low viscosity, is isotonic with blood and has a physiological pH. CONCLUSION:
      MnDPDP trisodium is a crystalline, hygroscopic solid which is readily soluble in
      water. No evidence of polymorphism was seen in the samples studied.

PMID- 9245975
TI  - Human female meiosis: new insights into an error-prone process.

PMID- 9245976
TI  - XIST expression and X-chromosome inactivation in human preimplantation embryos.

PMID- 9245977
TI  - When is a deletion not a deletion? When it is converted.

PMID- 9245978
TI  - Multilocus FISH analysis.

PMID- 9245979
TI  - Homologous recombination in human mitochondria?

PMID- 9245980
TI  - mtDNA recombination: what do in vitro data mean?

PMID- 9245981
TI  - First-meiotic-division nondisjunction in human oocytes.
AB  - Reject oocytes from in vitro-fertilization patients are currently the only
      practical source of human oocyte material available for meiotic studies in women.
      Two hundred clearly analyzable second meiotic (MII) metaphase oocytes from 116
      patients were examined for evidence of first meiotic (MI) division errors. The
      chromosome results, in which 67% of oocytes had a normal 23,X chromosome
      complement but none had an extra whole chromosome, cast doubt on the relevance,
      to human oocytes, of those theories of nondisjunction that propose that both
      chromosomes of the bivalent fail to disjoin at MI so that both move to one pole
      and result in an additional whole chromosome at MII metaphase. The only class of
      abnormality found in the MII oocytes had single chromatids (half-chromosomes)
      replacing whole chromosomes. Analysis of the chromosomally abnormal oocytes
      revealed an extremely close correlation with data on trisomies in spontaneous
      abortions, with respect to chromosome distribution, frequency, and maternal age,
      and indicated the likelihood of the chromatid abnormalities being the MI-division
      nondisjunction products that lead to trisomy formation after fertilization. The
      most likely derivation of the abnormalities is through a from of misdivision
      process usually associated with univalents, in which the centromeres divide
      precociously at MI, instead of MII, division. In the light of recent data that
      show that altered recombination patterns of the affected chromosomes are a key
      feature of most MI-division trisomies, the oocyte data imply that the vulnerable
      meiotic configurations arising from altered recombination patterns are processed
      as functional univalents in older women. Preliminary evidence from MI-metaphase
      oocytes supports this view.

PMID- 9245982
TI  - XIST expression in human oocytes and preimplantation embryos.
AB  - During mouse preimplantation development, the exclusive expression of the Xist
      gene from the paternally inherited allele is thought to play a role in the
      inactivation of the paternally inherited X chromosome in the extra-embryonic cell
      lineages of the developing female embryo. Recently, inactivation of the
      paternally inherited X chromosome has also been shown to occur in the
      extraembryonic cell lineages of the human female conceptus. In this paper, we
      determine whether the pattern of XIST expression in human preimplantation embryos
      is similarly correlated with paternal X inactivation. We developed procedures
      sensitive to the single cell, for the simultaneous analysis of XIST and HPRT
      expression and of sexing, initially using human fibroblast cells. Application of
      these procedures to human cleavage-stage embryos derived by in vitro
      fertilization revealed a pattern of XIST expression different from that in the
      mouse. Transcripts of the XIST gene were detected as early as the 1-cell zygote
      and, with increasing efficiency, through to the 8-cell stage of preimplantation
      development. In addition, transcripts of XIST were detected in both male (hence
      from the maternally inherited allele) and female preimplantation embryos. This
      pattern of expression is not consistent with a role for the early expression of
      the XIST gene in the choice of paternal X inactivation in the extraembryonic cell
      lineages of the developing human embryo.

PMID- 9245983
TI  - Genomic variation and gene conversion in spinal muscular atrophy: implications
      for disease process and clinical phenotype.
AB  - Autosomal recessive spinal muscular atrophy (SMA) is classified, on the basis of
      age at onset and severity, into three types: type I, severe; type II,
      intermediate; and type III, mild. The critical region in 5q13 contains an
      inverted repeat harboring several genes, including the survival motor neuron
      (SMN) gene, the neuronal apoptosis inhibitory protein (NAIP) gene, and the p44
      gene, which encodes a transcription-factor subunit. Deletion of NAIP and p44 is
      observed more often in severe SMA, but there is no evidence that these genes play
      a role in the pathology of the disease. In > 90% of all SMA patients, exons 7 and
      8 of the telomeric SMN gene (SMNtel) are not detectable, and this is also
      observed in some normal siblings and parents. Point mutations and gene
      conversions in SMNtel suggest that it plays a major role in the disease. To
      define a correlation between genotype and phenotype, we mapped deletions, using
      pulsed-field gel electrophoresis. Surprisingly, our data show that mutations in
      SMA types II and III, previously classed as deletions, are in fact due to gene
      conversion events in which SMNtel is replaced by its centromeric counterpart,
      SMNcen. This results in a greater number of SMNcen copies in type II and type III
      patients compared with type I patients and enables a genotype/phenotype
      correlation to be made. We also demonstrate individual DNA-content variations of
      several hundred kilobases, even in a relatively isolated population from Finland.
      This explains why no consensus map of this region has been produced. This DNA
      variation may be due to a midisatellite repeat array, which would promote the
      observed high deletion and gene-conversion rate.

PMID- 9245984
TI  - Simultaneous, multilocus FISH analysis for detection of microdeletions in the
      diagnostic evaluation of developmental delay and mental retardation.
AB  - Many microdeletion and contiguous gene-deletion syndromes include mental
      retardation as a clinical feature. We have developed MultiFISH, a FISH assay
      using several probes to simultaneously screen for multiple microdeletion
      syndromes in patients who present with unexplained devleopmental delay and/or
      mental retardation. This screening tool can be used to determine whether a
      particular microdeletion syndrome is involved in the etiology of these clinical
      phenotypes. In this pilot study we combined probes for the commonly deleted
      regions of Prader-Willi, Angelman, Williams, Smith-Magenis, and
      DiGeorge/velocardiofacial syndromes in a single hybridization. The probes were
      differentially labeled, allowing multicolor detection, and 200 individual samples
      were screened in a blinded fashion. For all patients found by MultiFISH to have
      deletions, the deletions were originally identified and/or later confirmed by use
      of single-probe FISH analysis in our diagnostic cytogenetics laboratory. One
      patient, who was referred for developmental delay and was shown to have a normal
      G-banded karyotype, was identified by MultiFISH as having a micro-deletion at the
      DiGeorge/velocardiofacial commonly deleted region. Forty-six of the 200 total
      samples were tested for microdeletions by use of single FISH probes in the
      diagnostic laboratory. Ten of these cases were found to have deletions, and all
      deletions were subsequently detected by use of MultiFISH screen performed in a
      blinded fashion. Additionally, for all 200 patients tested by use of MultiFISH,
      no false-positive deletion results were observed. We demonstrate the ability of
      this technique to scan for and to identify microdeletions in a proportion of
      patients whose routine karyotype appears normal yet who are mentally retarded
      and/or developmentally delayed.

PMID- 9245985
TI  - The activin receptor-like kinase 1 gene: genomic structure and mutations in
      hereditary hemorrhagic telangiectasia type 2.
AB  - The activin receptor-like kinase 1 gene (ALK-1) is the second locus for the
      autosomal dominant vascular disease hereditary hemorrhagic telangiectasia (HHT).
      In this paper we present the genomic structure of the ALK-1 gene, a type I serine
      threonine kinase receptor expressed predominantly in endothelial cells. The
      coding region is contained within nine exons, spanning < 15 kb of genomic DNA.
      All introns follow the GT-AG rule, except for intron 6, which has a TAG/gcaag 5'
      splice junction. The positions of introns in the intracellular domain are almost
      identical to those of the mouse serine-threonine kinase receptor TSK-7L. By
      sequencing ALK-1 from genomic DNA, mutations were found in six of six families
      with HHT either shown to link to chromosome 12q13 or in which linkage of HHT to
      chromosome 9q33 had been excluded. Mutations were also found in three of six
      patients from families in which available linkage data were insufficient to allow
      certainty with regard to the locus involved. The high rate of detection of
      mutations by genomic sequencing of ALK-1 suggests that this will be a useful
      diagnostic test for HHT2, particularly where preliminary linkage to chromosome
      12q13 can be established. In two cases in which premature termination codons were
      found in genomic DNA, the mutant mRNA was either not present or present at barely
      detectable levels. These data suggest that mutations in ALK-1 are functionally
      null alleles.

PMID- 9245986
TI  - Characterization of endoglin and identification of novel mutations in hereditary
      hemorrhagic telangiectasia.
AB  - To identify mutations that cause hereditary hemorrhagic telangiectasia (HHT, or
      Rendu-Osler-Weber syndrome), clinical evaluations and genetic studies were
      performed on 32 families. Linkage studies in four of eight families indicated an
      endoglin (ENG) gene mutation. ENG sequences of affected members of the four
      linked families and probands from the 24 small families were screened for
      mutations, by Southern blot analyses and by cycle sequencing of PCR-amplified
      DNA. Seven novel mutations were identified in eight families. Two mutations (a
      termination codon in exon 4 and a large genomic deletion extending 3' of intron
      8) did not produce a stable ENG transcript in lymphocytes. Five other mutations
      (two donor splice-site mutations and three deletions) produce altered mRNAs that
      are predicted to encode markedly truncated ENG proteins. Mutations in other
      families are predicted to lie in ENG-regulatory regions or in one of the
      additional genes that may cause HHT. These data suggest that the molecular
      mechanism by which ENG mutations cause HHT is haploinsufficiency. Furthermore,
      because the clinical manifestation of disease in these eight families was
      similar, we hypothesize that phenotypic variation of HHT is not related to a
      particular ENG mutation.

PMID- 9245987
TI  - Constitutively methylated CpG dinucleotides as mutation hot spots in the
      retinoblastoma gene (RB1).
AB  - A wide spectrum of mutations, ranging from point mutations to large deletions,
      have been described in the retinoblastoma gene (RB1). Mutations have been found
      throughout the gene; however, these genetic alterations do not appear to be
      homogeneously distributed. In particular, a significant proportion of disease
      causing mutations results in the premature termination of protein synthesis, and
      the majority of these mutations occur as C-->T transitions at CpG dinucleotides
      (CpGs). Such recurrent CpG mutations, including those found in RB1, are likely
      the result of the deamination of 5-methylcytosine within these CpGs. In the
      present study, we used the sodiumbisulfite conversion method to detect cytosine
      methylation in representative exons of RB1. We analyzed DNA from a variety of
      tissues and specifically targeted CGA codons in RB1, where recurrent premature
      termination mutations have been reported. We found that DNA methylation within
      RB1 exons 8, 14, 25, and 27 appeared to be restricted to CpGs, including six CGA
      codons. Other codons containing methylated cytosines have not been reported to be
      mutated. Therefore, disease-causing mutations at CpGs in RB1 appear to be
      determined by several factors, including the constitutive presence of DNA
      methylation at cytosines within CpGs, the specific codon within which the
      methylated cytosine is located, and the particular region of the gene within
      which that codon resides.

PMID- 9245988
TI  - Different mechanisms and recurrence risks of imprinting defects in Angelman
      syndrome.
AB  - Angelman syndrome (AS) is a neurogenetic disorder that appears to be caused by
      the loss of function of an imprinted gene expressed from maternal chromosome 15
      only. Approximately 6% of patients have a paternal imprint on the maternal
      chromosome. In the few cases, this is due to an inherited microdeletion, in the
      15q11-q13 imprinting center (IC), that blocks the paternal-->maternal imprint
      switch in the maternal germ line. We have determined the segregation of 15q11-q13
      haplotypes in nine families with AS and with an imprinting defect. One family,
      with two affected siblings, has a microdeletion affecting the IC transcript. In
      the other eight patients, no mutation was found at this locus. In two families,
      the patient and a healthy sibling share the same maternal alleles. In one of
      these families and in two others, grandparental DNA samples were available, and
      the chromosomes with the imprinting defect were found to be of grandmaternal
      origin. These findings suggest that germ-line mosaicism or de novo mutations
      account for a significant fraction of imprinting defects, among patients who have
      an as-yet-undetected mutation in a cis-acting element. Alternatively, these data
      may indicate that some imprinting defects are caused by a failure to maintain or
      to reestablish the maternal imprint in the maternal germ line or by a failure to
      replicate the imprint postzygotically. Depending on the underlying cause of the
      imprinting defect, different recurrence risks need to be considered.

PMID- 9245989
TI  - Definitive evidence for an autosomal recessive form of hypohidrotic ectodermal
      dysplasia clinically indistinguishable from the more common X-linked disorder.
AB  - A crucial issue in genetic counseling is the recognition of nonallelic genetic
      heterogeneity. Hypohidrotic (anhidrotic) ectodermal dysplasia (HED), a genetic
      disorder characterized by defective development of hair, teeth, and eccrine sweat
      glands, is usually inherited as an X-linked recessive trait mapped to the X
      linked ectodermal dysplasia locus, EDA, at Xq12-q13.1. The existence of an
      autosomal recessive form of the disorder had been proposed but subsequently had
      been challenged by the hypothesis that the phenotype of severely affected
      daughters born to unaffected mothers in these rare families may be due to marked
      skewing of X inactivation. Five families with possible autosomal recessive HED
      have been identified, on the basis of the presence of severely affected females
      and unaffected parents in single sibships and in highly consanguineous families
      with multiple affected family members. The disorder was excluded from the EDA
      locus by the lack of its cosegregation with polymorphic markers flanking the EDA
      locus in three of five families. No mutations of the EDA gene were detected by
      SSCP analysis in the two families not excluded by haplotype analysis. The
      appearance of affected males and females in autosomal recessive HED was
      clinically indistinguishable from that seen in males with X-linked HED. The
      findings of equally affected males and females in single sibships, as well as the
      presence of consanguinity, support an autosomal recessive mode of inheritance.
      The fact that phenotypically identical types of HED can be caused by mutations at
      both X-linked and autosomal loci is analogous to the situation in the mouse,
      where indistinguishable phenotypes are produced by mutations at both X-linked
      (Tabby) and autosomal loci (crinkled and downless).

PMID- 9245990
TI  - Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA
      trinucleotide repeat.
AB  - The Friedreich ataxia (FA) mutation has recently been identified as an unstable
      trinucleotide GAA repeat present 7-22 times in the normal population but
      amplified as many as > 1,000 times in FA. Since it is an autosomal recessive
      disease, FA does not show typical features observed in other dynamic mutation
      disorders, such as genetic anticipation. We have analyzed the GAA repeat in 104
      FA patients and 163 carrier relatives previously defined by linkage analysis. The
      GAA expansion was detected in all patients, most (94%) of them being homozygous
      for the mutation. We have demonstrated that clinical variability in FA is related
      to the size of the expanded alleles: milder forms of the disease-late-onset FA
      and FA with retained reflexes-are associated with shorter expansions, especially
      with the smaller of the two expanded alleles. Absence of cardiomyopathy is also
      associated with shorter alleles. Dynamics of the GAA repeat has been investigated
      in 212 parent-offspring pairs. Meiotic instability showed a sex bias: paternally
      transmitted alleles tend to decrease in a linear way that depends on the paternal
      expansion size, whereas maternal alleles can either increase or decrease. A
      different pattern of intergenerational variation was also observed, depending on
      the genetic status of the sib: patients had shorter expansions than were seen in
      heterozygous carriers. This finding has been interpreted as a postzygotic event.
      Finally, we have observed that the size of the expansion remains constant in the
      population through carriers.

PMID- 9245991
TI  - Identification of the human chromosomal region containing the
      iridogoniodysgenesis anomaly locus by genomic-mismatch scanning.
AB  - Genome-mismatch scanning (GMS) is a new method of linkage analysis that rapidly
      isolates regions of identity between two genomes. DNA molecules from regions of
      identity by descent from two relatives are isolated based on their ability to
      form extended mismatch-free heteroduplexes. We have applied this rapid technology
      to identify the chromosomal region shared by two fifth-degree cousins with
      autosomal dominant iridogoniodysgenesis anomaly (IGDA), a rare ocular
      neurocristopathy. Markers on the short arm of human chromosome 6p were recovered,
      consistent with the results of conventional linkage analysis conducted in
      parallel, indicating linkage of IGDA to 6p25. Control markers tested on a second
      human chromosome were not recovered. A GMS error rate of approximately 11% was
      observed, well within an acceptable range for a rapid, first screening approach,
      especially since GMS results would be confirmed by family analysis with selected
      markers from the putative region of identity by descent. These results
      demonstrate not only the value of this technique in the rapid mapping of human
      genetic traits, but the first application of GMS to a multicellular organism.

PMID- 9245992
TI  - Cancer risks in two large breast cancer families linked to BRCA2 on chromosome
      13q12-13.
AB  - The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estimated in two
      large, systematically ascertained, linked families, by use of a maximum
      likelihood method to incorporate both cancer-incidence data and 13q marker
      typings in the families. The cumulative risk of breast cancer in female gene
      carriers was estimated to be 59.8% by age 50 years (95% confidence interval [95%
      CI] 25.9%-78.5%) and 79.5% by age 70 years (95% CI 28.9%-97.5%). The cumulative
      risk of breast cancer in male carriers was estimated to be 6.3% (95% CI 1.4%
      25.6%) by age 70 years. There was no evidence of any risk difference between the
      two families. These results indicate that the lifetime breast cancer risk in
      BRCA2 carriers, for at least a subset of mutations, is comparable to that for
      BRCA1. A significant excess of ovarian cancer in gene carriers was observed
      (relative risk 17.69, based on three cases), but the absolute risk of ovarian
      cancer was less than that reported for BRCA1. Significant excesses of laryngeal
      cancer (relative risk 7.67, based on two possible carriers) and prostate cancer
      (relative risk 2.89, based on five possible carriers) were also observed. One
      case of ocular melanoma, as well as a second eye cancer of unspecified histology,
      occurred in obligate gene carriers.

PMID- 9245993
TI  - Reduced frequency of extracolonic cancers in hereditary nonpolyposis colorectal
      cancer families with monoallelic hMLH1 expression.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant
      disease caused by mutations in one of at least four different DNA mismatch repair
      genes, hMLH1, hMSH2, hPMS1, and hPMS2. Phenotypically, HNPCC is characterized by
      the early onset of colorectal cancers and various extracolonic cancers. Depending
      on the presence or absence of extracolonic tumors, HNPCG-has been divided into
      two syndromes (Lynch syndrome I and Lynch syndrome II), but, so far, no
      correlation to distinct genotypes has been demonstrated. In this study, we
      present a frequent hMLH1 intron 14 founder mutation that is associated with a
      highly reduced frequency of extracolonic tumors. The mutation disrupts the splice
      donor site and silences the mutated allele. Tumors exhibited microsatellite
      instability, and loss of the wild-type hMLH1 allele was prevalent. We propose
      that the mutation results in a milder phenotype, because the mutated hMLH1
      protein is prevented from exerting a dominant negative effect on the concerted
      action of the mismatch repair system.

PMID- 9245994
TI  - Linkage of Niemann-Pick disease type D to the same region of human chromosome 18
      as Niemann-Pick disease type C.
AB  - Niemann-Pick type II disease is a severe disorder characterized by accumulation
      of tissue cholesterol and sphingomyelin and by progressive degeneration of the
      nervous system. This disease has two clinically similar subtypes, type C (NPC)
      and type D (NPD). NPC is clinically variable and has been identified in many
      ethnic groups. NPD, on the other hand, has been reported only in descendants of
      an Acadian couple who lived in Nova Scotia in the early 18th century and has a
      more homogeneous expression resembling that of less severely affected NPC
      patients. Despite biochemical differences, it has not been established whether
      NPC and NPD are allelic variants of the same disease. We report here that NPD is
      tightly linked (recombination fraction .00; maximum LOD score 4.50) to a
      microsatellite marker, D18S480, from the centromeric region of chromosome 18q.
      Carstea et al. have reported that the NPC gene maps to this same site; therefore
      we suggest that NPC and NPD likely result from mutations in the same gene.

PMID- 9245995
TI  - The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21,
      between D18S849 and D18S1103.
AB  - Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive
      coagulation disorder in which the levels of both coagulation factor V and
      coagulation factor VIII are diminished. In order to map and subsequently clone
      the gene responsible for this phenotype, DNAs from 19 families (16 from Iran, 2
      from Pakistan, and 1 from Algeria) with a total of 32 affected individuals were
      collected for a genomewide linkage search using genotypes of highly informative
      DNA polymorphisms. All pedigrees except two contained at least one consanguineous
      marriage. A maximum LOD score (Zmax) of 14.82 for theta = .02 was generated with
      marker D18S1129 in 18q21; LOD scores > 9 were obtained for several other markers
      D18S849, D18S1103, D18S64, and D18S862. Multipoint analysis resulted in Zmax =
      18.91 for the interval between D18S1129 and D18S64. Informative recombinants
      placed the locus for F5F8D between D18S849 and D18S1103, in an interval of
      approximately 1 cM. These results are similar to the recently reported linkage of
      this disease to chromosome 18q in Jewish families (Nichols et al. 1997) and
      provide evidence that the same gene is responsible for all F5F8D among human
      populations. The difference in clinical severity of the phenotype in unrelated
      families, as well as the failure to detect a specific haplotype of DNA
      polymorphisms in the consanguineous Iranian families, suggests the existence of
      different molecular defects in the F5F8D gene. There exists an apparently gap
      free contig with CEPH YACs linking the two markers on either side of the critical
      region. Positional cloning efforts are now in progress to clone the F5F8D gene.

PMID- 9245996
TI  - The seventh form of autosomal recessive limb-girdle muscular dystrophy is mapped
      to 17q11-12.
AB  - The group of autosomal recessive (AR) muscular dystrophies includes, among
      others, two main clinical entities, the limb-girdle muscular dystrophies (LGMDs)
      and the distal muscular dystrophies. The former are characterized mainly by
      muscle wasting of the upper and lower limbs, with a wide range of clinical
      severity. This clinical heterogeneity has been demonstrated at the molecular
      level, since the genes for six AR forms have been cloned and/or have been mapped
      to 15q15.1 (LGMD2A), 2p12-16 (LGMD2B), 13q12 (LGMD2C), 17q12-q21.33 (LGMD2D),4q12
      (LGMD2E), and 5q33-34 (LGMD2F). The AR distal muscular dystrophies originally
      included two subgroups, Miyoshi myopathy, characterized mainly by extremely
      elevated serum creatine kinase (CK) activity and by a dystrophic muscle pattern,
      and Nonaka myopathy, which is distinct from the others because of the normal to
      slightly elevated serum CK levels and a myopathic muscle pattern with rimmed
      vacuoles. With regard to our unclassified AR LGMD families, analysis of the
      affected sibs from one of them (family LG61) revealed some clinical and
      laboratory findings (early involvement of the distal muscles, mildly elevated
      serum CK levels, and rimmed vacuoles in muscle biopsies) that usually are not
      observed in the analysis of patients with LGMD2A-LGMD2F. In the present
      investigation, through a genomewide search in family LG61, we demonstrated
      linkage of the allele causing this form of muscular dystrophy to a 3-cM region on
      17q11-12. We suggest that this form, which, interestingly, clinically resembles
      AR Kugelberg-Welander disease, should be classified as LGMD2G. In addition, our
      results indicate the existence of still another locus causing severe LGMD.

PMID- 9245997
TI  - Familial skewed X inactivation: a molecular trait associated with high
      spontaneous-abortion rate maps to Xq28.
AB  - We report a family ascertained for molecular diagnosis of muscular dystrophy in a
      young girl, in which preferential activation (> or = 95% of cells) of the
      paternal X chromosome was seen in both the proband and her mother. To determine
      the molecular basis for skewed X inactivation, we studied X-inactivation patterns
      in peripheral blood and/or oral mucosal cells from 50 members of this family and
      from a cohort of normal females. We found excellent concordance between X
      inactivation patterns in blood and oral mucosal cell nuclei in all females. Of
      the 50 female pedigree members studied, 16 showed preferential use (> or = 95%
      cells) of the paternal X chromosome; none of 62 randomly selected females showed
      similarly skewed X inactivation was maternally inherited in this family. A
      linkage study using the molecular trait of skewed X inactivation as the scored
      phenotype localized this trait to Xq28 (DXS1108; maximum LOD score [Zmax] = 4.34,
      recombination fraction [theta] = 0). Both genotyping of additional markers and
      FISH of a YAC probe in Xq28 showed a deletion spanning from intron 22 of the
      factor VIII gene to DXS115-3. This deletion completely cosegregated with the
      trait (Zmax = 6.92, theta = 0). Comparison of clinical findings between affected
      and unaffected females in the 50-member pedigree showed a statistically
      significant increase in spontaneous-abortion rate in the females carrying the
      trait (P < .02). To our knowledge, this is the first gene-mapping study of
      abnormalities of X-inactivation patterns and is the first association of a
      specific locus for recurrent spontaneous abortion in a cytogenetically normal
      family. The involvement of this locus in cell lethality, cell-growth
      disadvantage, developmental abnormalities, or the X-inactivation process is
      discussed.

PMID- 9245998
TI  - Evidence that the apolipoprotein E-genotype effects on lipid levels can change
      with age in males: a longitudinal analysis.
AB  - We previously reported that change, with age, in plasma levels of total
      cholesterol (TC) and LDL cholesterol (LDL-C) differed between apolipoprotein E
      (APOE) genotypes epsilon 3 epsilon 3 and epsilon 3 epsilon 4, in a sample of 77
      older, unrelated males. By use of a larger sample from that cohort, followed
      longitudinally during 1969-87, the change in TC and in LDL-C, between the epsilon
      3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes, over three exams, was
      reanalyzed. Additionally, the change in triglycerides (TG) and in HDL-cholesterol
      (HDL-C), between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes
      as well as the differences between the epsilon 3 epsilon 3 and epsilon 3 epsilon
      2 genotypes, for TC, LDL-C, TG, and HDL-C-were contrasted over the three exams.
      At exam 1 TG was higher in the epsilon 3 epsilon 4 group than in the epsilon 3
      epsilon 3 group (mean age 48 years), and at exams 2 and exam 3 (mean ages 58 and
      63 years, respectively) it was similar (P = .009 for the exam-by-genotype
      interaction effect in the repeated-measures analysis). A similar trend was seen
      for TC (P = .03), yet previously detected LDL-C effects were not apparent (P =
      .46). Those with the epsilon 3 epsilon 2 genotype had higher TG and lower LDL-C
      and TC at each exam than were seen in those with the epsilon 3 epsilon 3
      genotype, although the differences in the values were not always statistically
      significant. Differences in TC, LDL-C, and TG, between the epsilon 3 epsilon 2
      genotype and epsilon 3 epsilon 3-genotype groups, did not significantly change
      over the three exams. HDL-C levels were relatively stable over the exams;
      however, the exam-by-genotype interaction was significant for the epsilon 3
      epsilon 2 genotype versus the epsilon 3 epsilon 3 genotype (P = .02). The epsilon
      4 allele effects on TG and TC changed between longitudinal exams and may be age
      dependent. Changes, with age, in the effect of the epsilon 3 epsilon 4 genotype
      on lipids may impact the risk of developing atherosclerotic disease.

PMID- 9246000
TI  - Testing association between candidate-gene markers and phenotype in related
      individuals, by use of estimating equations.
AB  - Association studies are one of the major strategies for identifying genetic
      factors underlying complex traits. In samples of related individuals,
      conventional statistical procedures are not valid for testing association, and
      maximum likelihood (ML) methods have to be used, but they are computationally
      demanding and are not necessarily robust to violations of their assumptions.
      Estimating equations (EE) offer an alternative to ML methods, for estimating
      association parameters in correlated data. We studied through simulations the
      behavior of EE in a large range of practical situations, including samples of
      nuclear families of varying sizes and mixtures of related and unrelated
      individuals. For a quantitative phenotype, the power of the EE test was
      comparable to that of a conventional ML test and close to the power expected in a
      sample of unrelated individuals. For a binary phenotype, the power of the EE test
      decreased with the degree of clustering, as did the power of the ML test. This
      result might be partly explained by a modeling of the correlations between
      responses that is less efficient than that in the quantitative case. In small
      samples (< 50 families), the variance of the EE association parameter tended to
      be underestimated, leading to an inflation of the type I error. The heterogeneity
      of cluster size induced a slight loss of efficiency of the EE estimator, by
      comparison with balanced samples. The major advantages of the EE technique are
      its computational simplicity and its great flexibility, easily allowing
      investigation of gene-gene and gene-environment interactions. It constitutes a
      powerful tool for testing genotype-phenotype association in related individuals.

PMID- 9245999
TI  - Fc epsilon R1-beta polymorphism and total serum IgE levels in endemically
      parasitized Australian aborigines.
AB  - Endemic helminthic infection is a major public-health problem and affects a large
      proportion of the world's population. In Australia, helminthic infection is
      endemic in Aboriginal communities living in tropical northern regions of the
      continent. Such infection is associated with nonspecific (polyclonal) stimulation
      of IgE synthesis and highly elevated total serum IgE levels. There is evidence
      that worm-infection variance (i.e., human capacity of resistance) and total serum
      IgE levels may be related to the presence of a major codominant gene. The beta
      chain of the high-affinity IgE receptor, Fc epsilon R1-beta, has been previously
      identified as a candidate for the close genetic linkage of the 11q13 region to
      IgE responses in several populations. We show a biallelic RsaI polymorphism in Fc
      epsilon R1-beta to be associated with total serum IgE levels (P = .0001) in a
      tropical population of endemically parasitized Australian Aborigines (n = 234
      subjects). The polymorphism explained 12.4% of the total residual variation in
      serum total IgE and showed a significant (P = .0000) additive relationship with
      total serum IgE levels, across the three genotypes. These associations were
      independent of familial correlations, age, gender, racial admixture, or smoking
      status. Alleles of a microsatellite repeat in intron 5 of the same gene showed
      similar associations. The results suggest that variation in Fc epsilon R1-beta
      may regulate IgE-mediated immune responses in this population.

PMID- 9246001
TI  - A linkage strategy for detection of human quantitative-trait loci. I. Generalized
      relative risk ratios and power of sib pairs with extreme trait values.
AB  - We generalize the concept of the relative risk ratio (lambda) to the case of
      quantitative traits, to take into account the various trait outcomes of a
      relative pair. Formulas are derived to express the expected proportions of genes
      shared identical by descent by a sib pair, in terms of the generalized lambda's
      for sib pairs (lambda S), parent-offspring pairs (lambda O), and monozygotic
      twins (lambda M) and in terms of the recombination fraction, with the assumption
      of no residual correlations. If residual correlations are nonzero among relative
      pairs, we assume that they are the same among sib pairs, parent-offspring pairs,
      and monozygotic twins, and we employ a slightly different definition for the
      generalized lambda so that the same set of formulas still hold. The power (or,
      the sample size necessary) to detect quantitative-trait loci (QTLs) by use of
      extreme sib pairs (ESPs) is shown to be a function of the three generalized
      lambda's. Since lambda M can be derived by use of values of lambda S and lambda
      O, estimates of the latter two lambda's will suffice for the analysis of power
      and the necessary sample sizes of ESPs, for a QTL linkage study.

PMID- 9246002
TI  - A linkage strategy for detection of human quantitative-trait loci. II.
      Optimization of study designs based on extreme sib pairs and generalized relative
      risk ratios.
AB  - We are concerned here with practical issues in the application of extreme sib
      pair (ESP) methods to quantitative traits. Two important factors-namely, the way
      extreme trait values are defined and the proportions in which different types of
      ESPs are pooled, in the analysis-are shown to determine the power and the cost
      effectiveness of a study design. We found that, in general, combining reasonable
      numbers of both extremely discordant and extremely concordant sib pairs that were
      available in the sample is more powerful and more cost effective than pursuing
      only a single type of ESP. We also found that dividing trait values with a less
      extreme threshold at one end or at both ends of the trait distribution leads to
      more cost-effective designs. The notion of generalized relative risk ratios (the
      lambda methods, as described in the first part of this series of two articles) is
      used to calculate the power and sample size for various choices of
      polychotomization of trait values and for the combination of different types of
      ESPs. A balance then can be struck among these choices, to attain an optimum
      design.

PMID- 9246003
TI  - Variable age at onset in insulin-dependent diabetes mellitus, by the marker
      association-segregation-chi 2 method.
AB  - The marker-association-segregation-chi 2 (MASC) method with consideration of age,
      for nonaffected persons, and of age at onset, for affected persons, was applied
      to a sample of 308 HLA-typed families. Hazard rates modeling the instantaneous
      risk of catching the disease were estimated under the exponential distribution
      and with satisfactory goodness of fit. This class of models shows that the
      hypothesis of the absence of parental imprinting cannot be rejected for insulin
      dependent diabetes mellitus.

PMID- 9246004
TI  - Inter- and intrachromosomal rearrangements are both involved in the origin of
      15q11-q13 deletions in Prader-Willi syndrome.

PMID- 9246005
TI  - DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a
      modifying mitochondrial gene and show no evidence for a modifying nuclear gene.

PMID- 9246007
TI  - Nonreplication of linkage disequilibrium between the dopamine D4 receptor locus
      and Tourette syndrome.

PMID- 9246006
TI  - A C2055T transition in exon 8 of the ATP7A gene is associated with exon skipping
      in an occipital horn syndrome family.

PMID- 9246009
TI  - Diagnostic testing for Prader-Willi and Angelman syndromes: response.

PMID- 9246008
TI  - Exclusion of atypical vitelliform macular dystrophy from 8q24.3 and from other
      known macular degenerative loci.

PMID- 9246010
TI  - Further comments on the characterization of founder Amerindian mitochondrial
      haplotypes.

PMID- 9246011
TI  - Paleolithic and Neolithic lineages in the European mitochondrial gene pool.

PMID- 9246012
TI  - Nonparametric linkage tests are model free.

PMID- 9246013
TI  - Bias against the null hypothesis in maternal-fetal pharmacology and toxicology.

PMID- 9246014
TI  - Impairment of the metabolism of dipyrone in asymptomatic carriers of the
      hepatitis B virus.
AB  - BACKGROUND: The pharmacokinetics of a number of drugs has been shown to be
      impaired in patients with acute or chronic viral liver disease. OBJECTIVE: To
      examine the effect of the asymptomatic hepatitis B virus carrier state on the
      metabolism of dipyrone (INN, metamizole) as a model drug. METHODS: The
      pharmacokinetics of the metabolites of dipyrone-4-methylaminoantipyrine, 4
      aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine-after a 1.0
      gm oral dose of dipyrone were evaluated in nine asymptomatic carriers of
      hepatitis B virus with normal liver function tests and nine healthy subjects. All
      subjects displayed the slow acetylator phenotype. RESULTS: The nonrenal
      (metabolic) clearance of 4-methylaminoantipyrine was significantly reduced (mean
      +/- SEM) (123.3 +/- 15.8 versus 182.9 +/- 15.1 ml.min-1, respectively; p < 0.02)
      in the carriers of hepatitis B virus compared with the healthy subjects, and the
      elimination half-life of this metabolite was significantly longer (3.69 +/- 0.35
      versus 2.64 +/- 0.28 hours, respectively; p < 0.03). The formation clearances of
      4-aminoantipyrine and 4-formylaminoantipyrine were significantly smaller in the
      carriers of hepatitis B virus compared with healthy subjects (33.8 +/- 6.2 versus
      55.2 +/- 6.4 ml.min-1; p < 0.03, and 16.7 +/- 2.2 versus 34.2 +/- 4.2 ml.min-1; p
      < 0.002; respectively). However, the elimination half-life of 4
      formylaminoantipyrine was found to be slightly shorter in the carriers of
      hepatitis B virus. No significant differences were noted between the groups in
      the pharmacokinetics of 4-acetylaminoantipyrine. CONCLUSION: The metabolism of
      dipyrone is impaired in asymptomatic carriers of hepatitis B virus. Clinically
      latent infection with hepatitis B virus seems to exert a differential effect on
      metabolism of the drug. Oxidative pathways to produce 4-aminoantipyrine and 4
      formylaminoantipyrine were significantly affected, whereas acetylation remained
      intact. This study provided an additional example of the effect of a virus on the
      disposition of a drug.

PMID- 9246015
TI  - Population pharmacokinetics of high-dose thiopental in patients with cerebral
      injuries.
AB  - Thiopental monitoring was performed in 95 critically ill patients hospitalized
      for neurologic damage, High-dose thiopental was infused during long-term
      treatment. Total dose of 333 +/- 144 mg/kg (449 +/- 185 mg/kg for females and 302
      +/- 113 mg/kg for men) were given in 125 +/- 43 hours. Plasma concentration-time
      data were analyzed according to a population pharmacokinetic approach with an
      initial group of 65 patients. Clearance (CL) and central volume of distribution
      (Vc) were modeled alone and under the influence of demographic covariates,
      assuming a two-compartment open model with first-order elimination. The final
      population models were as follows: CL (L/hr) = 11.7.weight (kg).age (yr)/(2136 +
      age2) and Vc = 1.52.weight (kg) + 44.8. Mean CL and Vc mean population estimates
      were 8.01 L/hr (133 ml/min or 2.02 ml/min/kg) and 145 L (2.19 L/kg). The
      predictive performance of the population modeling and parameters was evaluated
      with a bayesian fitting procedure in an independent validation set of 30 patients
      with similar physical and clinical characteristics. There was no statistically
      significant bias or imprecision between measured and predicted thiopental plasma
      concentrations in this validation group. Moreover, there was a good adequation (r
      = 0.939) between individual CL values predicted from the population formula and
      estimated with the bayesian approach.

PMID- 9246016
TI  - The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and
      slow metabolizers of S-mephenytoin.
AB  - Omeprazole, a widely used and potent gastric proton pump inhibitor, induces
      cytochrome P450 (CYP) 1A2 in humans. Induction is most pronounced in slow
      metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is
      responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol),
      a widely used and effective analgesic and antipyretic agent, causes serious
      hepatic and renal toxicity at high doses by conversion of acetaminophen to the
      toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) through CYP1A2, CYP2E1,
      and CYP3A4. This study evaluated whether omeprazole pretreatment in five rapid
      and five slow metabolizers of S-mephenytoin could increase thioether (an estimate
      of NAPQI production) metabolite formation from acetaminophen. The results of this
      study show that, despite induction of CYP1A2 activity in slow metabolizers (a 75%
      increase in plasma clearance of caffeine), the formation of NAPQI from
      acetaminophen was not increased after 7 days of omeprazole administration (40
      mg/day). This suggests that induction of CYP1A2 activity by omeprazole is
      unlikely to increase the risk of acetaminophen hepatotoxicity.

PMID- 9246017
TI  - Fuzzy logic pharmacokinetic modeling: application to lithium concentration
      prediction.
AB  - INTRODUCTION: We hypothesized that fuzzy logic could be used for pharmacokinetic
      modeling. Our objectives were to develop and evaluate a model for predicting
      serum lithium concentrations with fuzzy logic. METHODS: Steady-state
      pharmacokinetic data had been previously collected in 10 elderly patients (age
      range, 67 to 80 years) with depression who were receiving lithium once daily.
      Each patient had serial serum lithium concentration determinations over one 24
      hour period. The resulting 137 data sets initially consisted of five input
      variables (age, weight, serum creatinine, lithium dose, and time since last dose)
      and one output variable (serum lithium concentration; range, 0.2 to 1.24 mmol/L).
      RESULTS: A fuzzy rulebase was created with 87 randomly chosen data sets, and
      predictions of serum lithium concentration were made on the basis of the
      remaining 50 data sets. All of the input variables except age and weight were
      identified as contributing to the fuzzy logic model. The average magnitude of the
      error in the predictions was 0.13 mmol/L (root mean squared error) with a bias
      (mean of the prediction errors) of 0.03 mmol/L. CONCLUSIONS: This study indicates
      that the use of fuzzy logic for pharmacokinetic modeling of lithium for serum
      concentration predictions is feasible.

PMID- 9246018
TI  - Tacrolimus oral bioavailability doubles with coadministration of ketoconazole.
AB  - OBJECTIVE: To quantitate the effect of ketoconazole, an azole antifungal agent
      and potent inhibitor of CYP3A4 and P-glycoprotein, on the bioavailability of
      tacrolimus, a substrate of the CYP3A system and of P-glycoprotein. SUBJECTS AND
      METHODS: The pharmacokinetics of tacrolimus were studied in six healthy
      volunteers (two women and four men) in a four-dose study after each received
      single doses of tacrolimus alone (0.1 mg/kg orally and 0.025 mg/kg intravenously)
      and with coadministered ketoconazole (200 mg orally at bedtime for 12 days). The
      dose of tacrolimus was reduced during the ketoconazole phase (0.04 mg/kg orally;
      0.01 mg/kg intravenously). Ketoconazole and tacrolimus doses were separated by
      approximately 10 hours. Whole blood tacrolimus concentrations were determined by
      enzyme-linked immunosorbent assay. Estimated pharmacokinetic parameters in whole
      blood (mean +/- SD) before and with ketoconazole were calculated with
      noncompartmental techniques. RESULTS: Coadministration of ketoconazole did not
      consistently affect tacrolimus clearance (55.6 +/- 16.7 ml/hr/kg versus 42.5 +/-
      7.6 ml/hr/kg), and steady-state volume of distribution was unchanged (0.99 +/-
      0.26 L/kg versus 0.93 +/- 0.25 L/kg). However, a significant increase in
      tacrolimus bioavailability (14% +/- 5% versus 30% +/- 8%; p < 0.01) was observed
      with coadministered ketoconazole. Hepatic bioavailability was unchanged by the
      presence of ketoconazole (96% +/- 1% versus 97% +/- 1%). CONCLUSIONS: Because
      ketoconazole did not alter hepatic bioavailability and because 10 hours separated
      administration times of the drugs, it appears that the marked increase in
      tacrolimus bioavailability can be explained by ketoconazole having a local
      inhibitory effect on tacrolimus gut metabolism or on intestinal P-glycoprotein
      activity.

PMID- 9246019
TI  - Effect of renal impairment on the pharmacokinetics and pharmacodynamics of
      desirudin.
AB  - OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of desirudin
      in subjects with various degrees of renal impairment in comparison with subjects
      with normal renal function. METHODS: Eight subjects with normal renal function
      (creatinine clearance > 90 ml/min) received 0.5 mg/kg desirudin intravenously
      over 30 minutes. Four subjects with mild renal failure (creatinine clearance
      between 61 and 90 ml/min) received 0.5 mg/kg. Five subjects with moderate renal
      failure (creatinine clearance between 31 and 60 ml/min) received 0.25 mg/kg. Six
      subjects with severe renal failure (creatinine clearance < 31 ml/min) received
      0.125 mg/kg. RESULTS: Specific maximum concentration values (maximum
      concentrations corrected to a dose of 1 mg/kg) increased slightly with decreasing
      creatinine clearance. Mean specific area under the plasma concentration-time
      curve increased by a factor of 1.15, 2.83, and 7.0 for subjects with mild,
      moderate, and severe renal failure, respectively, compared with healthy subjects.
      Total urinary excretion of desirudin was about 55% to 60% of the dose in all four
      groups; elimination was delayed for subjects with moderate and severe renal
      failure. Total and renal clearance of desirudin were proportional to creatinine
      clearance. Total plasma clearance of desirudin was proportional to renal
      clearance of the drug. Prolongation of activated partial thromboplastin time was
      increased among subjects with moderate and severe renal failure despite a dose
      reduction. Area under the dynamic activated partial thromboplastin time curve for
      subjects with moderate renal failure remained the same as that for healthy
      subjects despite a dose reduction by a factor of two. Area under the dynamic
      curve increased by a factor of about 1.5 for subjects with severe renal failure
      despite a dose reduction by a factor of four. CONCLUSION: A dose reduction by a
      factor of six is recommended for persons with severe renal failure.

PMID- 9246020
TI  - Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms.
AB  - Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine
      drugs. TPMT activity is regulated by a common genetic polymorphism that is
      associated with large individual variations in thiopurine toxicity and efficacy.
      We previously cloned the functional gene for human TPMT and reported a common
      variant allele for low enzyme activity, TPMT*3A, that contains point mutations at
      cDNA nucleotides 460 and 719. In the present study, we set out to determine the
      number, types, and frequencies of TPMT variant alleles associated with low enzyme
      activity in clinical laboratory samples in the United States and to compare those
      results with data obtained from two different ethnic groups. We identified a
      total of six different variant alleles for low TPMT activity in the 283 clinical
      laboratory samples studied. The most common variant was *3A; the second most
      frequent variant allele, *3C, contained only the nucleotide 719 polymorphism; and
      four other variant alleles were detected. TPMT*3A also appeared to be the most
      common variant allele in a Norwegian white population sample, but it was not
      found in a population sample of Korean children. However, *3C was present in
      samples from the Korean children, as was novel allele, *6. Characterization of
      variant alleles for low TPMT enzyme activity will help make it possible to assess
      the potential clinical utility of deoxyribonucleic acid-based diagnostic tests
      for determining TPMT genotype.

PMID- 9246021
TI  - Ibuprofen elevates immunoreactive beta-endorphin levels in humans during surgical
      stress.
AB  - Release of beta-endorphin is modulated by physiologic stress and a variety of
      hormonal and pharmacologic factors. Prostaglandin E2 inhibits release of beta
      endorphin and corticotropin from pituitary corticotroph cells, suggesting that
      suppression of prostaglandin levels should increase beta-endorphin release. This
      hypothesis was tested by administration of 600 mg ibuprofen before surgical
      stress in humans in comparison to placebo and methylprednisolone. Plasma samples
      were analyzed for immunoreactive beta-endorphin with concurrent measurement of
      pain and apprehension. Levels of immunoreactive beta-endorphin increased during
      surgery in the placebo group but were significantly greater in the group of
      patients pretreated with ibuprofen. Methylprednisolone suppressed intraoperative
      immunoreactive beta-endorphin, compared with both placebo and ibuprofen. Parallel
      in vivo and in vitro studies indicate that nonsteroidal anti-inflammatory drug
      potentiation of endorphin release is mediated at the level of the pituitary
      corticotroph cell. These results show that ibuprofen enhances pituitary release
      of beta-endorphin by corticotroph cells in response to stress.

PMID- 9246022
TI  - Plasma cholesteryl ester transfer protein is lowered by treatment of
      hypercholesterolemia with cholestyramine.
AB  - Cholestyramine (INN, colestyramine) treatment of subjects with
      hypercholesterolemia reduced the plasma level of cholesteryl ester transfer
      protein (CETP) as measured by radioimmunoassay (CETP-RIA) and, as expected, also
      reduced the levels of total cholesterol, low-density lipoprotein (LDL)
      cholesterol, and apolipoprotein B. The extent of CETP variation was significant
      only in the subjects whose LDL cholesterol levels were reduced by more than 25%.
      Furthermore, CETP-RIA was correlated with total cholesterol, LDL cholesterol, and
      apolipoprotein B concentrations. Plasma CETP was also measured by an indirect
      procedure that uses high-density lipoprotein (HDL) 14C-cholesteryl ester and very
      low-density lipoprotein cholesterol from a pool of plasma donors, and the
      patient's plasma as the source of CETP. The two procedures for CETP determination
      correlated well with each other, although the CETP-RIA was more sensitive in the
      detection of changes of plasma CETP ascribed to cholestyramine (INN,
      colestyramine) treatment. The rise of plasma HDL cholesterol levels after
      cholestyramine probably resulted from the reduction of CETP activity.

PMID- 9246023
TI  - A randomized double-blind study of carbamazepine in the treatment of cocaine
      abuse.
AB  - A 12-week, randomized, double-blind, placebo-controlled, fixed-dose outpatient
      study of carbamazepine (400 mg and 800 mg) in the treatment of cocaine dependence
      was performed. Data were analyzed with respect to both treatment condition and
      carbamazepine serum levels. Outcome variables included subject retention, cocaine
      urinalysis, self-reported cocaine use, cocaine craving, patient and clinical
      global impressions, the Drug Impairment Rating Scale for Cocaine, and side
      effects. Compared with placebo, the 400 mg treatment condition exhibited a
      greater decrease in the rate of positive cocaine urinalyses and a reduction in
      intensity and duration of craving over the course of the study. Higher serum
      carbamazepine levels were associated with a lower rate of positive cocaine
      urinalysis, fewer days of self-reported cocaine use, briefer craving episodes,
      and greater subject interval retention. The clinical and methodologic
      implications of these findings and of the study design are discussed.

PMID- 9246025
TI  - Reliability of screening procedures in identifying subjects suitable for
      enrollment in clinical pharmacology studies.

PMID- 9246024
TI  - Circadian variations in serum levels and the renal toxicity of aminoglycosides in
      patients.
AB  - Animals show a faster clearance and a lower incidence of nephrotoxicity and
      ototoxicity when aminoglycosides are administered during the activity period.
      Human data on a circadian rhythm in pharmacokinetics are conflicting, and there
      are no data on a circadian rhythm in toxicity. When aminoglycosides are
      administered once daily, as is often done, a circadian rhythm in pharmacokinetics
      or toxicity could have clinical implications. In a prospective study we
      investigated the influence of drug administration time on serum drug levels and
      the incidence of nephrotoxicity in 221 patients with serious infections treated
      with gentamicin or tobramycin once daily. We did not find statistically
      significant differences in trough or peak levels for the three time periods
      (midnight to 7:30 AM, 8 AM to 3:30 PM, and 4 to 11:30 PM). Nephrotoxicity
      occurred significantly more frequently when the aminoglycosides were administered
      during the rest period (midnight to 7:30 AM; p = 0.004). In addition to the
      coadministration of high-dose furosemide or other nephrotoxic antibiotics and the
      duration of treatment, the time of administration was still an independent risk
      factor in a multivariate analysis.

PMID- 9246026
TI  - What can be measured from surface electrogastrography. Computer simulations.
AB  - The aims of this study were to investigate the detectability of the propagation
      of the gastric slow wave from the cutaneous electrogastrogram (EGG) and the
      patterns of the EGG when the gastric slow waves are uncoupled. A mathematical
      model was established based on the volume conductor theory to simulate the
      transfer of the serosal gastric slow wave from the stomach to the abdominal
      surface. A number of computer simulations were conducted using the model, and the
      periodic cross-correlation function was used to estimate the phase shift between
      the four channels. It was found that the propagation of the gastric slow wave was
      detectable from the multichannel EGG signals. The detectability of the
      propagation was, however, associated with a number of factors, such as the
      thickness of the abdominal wall and the propagation velocity of the serosal slow
      wave. The amplitude of the EGG was found to be associated with the
      coupling/uncoupling and propagation velocity of the gastric slow wave. The
      amplitude of the EGG increased when the propagation velocity of the gastric slow
      wave increased. The amplitude of the EGG was substantially decreased when the
      gastric slow waves were uncoupled. The uncoupling of the gastric slow wave at a
      frequency of 3 cpm produced dysrhythmias in the EGG, including tachygastria,
      bradygastria, and arrhythmia. The power spectra of simulated different positional
      EGG signals showed similar patterns when the gastric slow wave was coupled and
      different and unpredictable patterns when the gastric slow wave was uncoupled. In
      conclusion, multichannel EGG recordings may be necessary to obtain more
      information on gastric slow waves from the abdominal electrodes. The propagation
      and coupling or uncoupling of the gastric slow wave may be detected from
      multichannel EGG recordings.

PMID- 9246029
TI  - Esophagoprotective potential of cisapride. An additional benefit for
      gastroesophageal reflux disease.
AB  - Cisapride is a novel prokinetic agent that releases acetylcholine at the level of
      the myenteric plexus. Acetylcholine also plays a role in the secretory function
      of salivary glands evoked by intraesophagal mechanical and chemical stimulation,
      mediated through the esophagosalivary reflex. The impact, however, of cisapride
      on salivary protective components mediated by esophagosalivary reflex remains
      unknown. Therefore, we have studied salivary pH, bicarbonate, nonbicarbonate,
      glycoconjugate, protein, EGF, TGF-alpha, and PGE2 before and after the
      administration of cisapride. The study was conducted in 20 asymptomatic
      volunteers (9 women and 11 men, mean age 36, range 26-52). Salivary secretions
      were collected under basal conditions and during masticatory, mechanical, and
      chemical stimulation before and after four days of cisapride administration (10
      or 20 mg four times a day). Cisapride administration resulted in a 45% increase
      in salivary volume during the basal condition (P < 0.01), a 32% increase during
      mastication (P < 0.05), a 53% increase during mechanical (P < 0.05), and a 51%
      increase during chemical (P < 0.01) stimulation. Cisapride administration
      resulted also in a significant increase in salivary protein output (P < 0.05),
      salivary bicarbonate (P < 0.05), and nonbicarbonate buffers (P < 0.05), and
      salivary EGF (P < 0.05). Salivary glycoconjugate significantly increased only
      during mechanical stimulation with the catheter and at the end of the esophageal
      perfusion procedure (P < 0.05). Although a similar trend was also recorded during
      the analysis of salivary PGE2, this difference did not reach statistical
      significance. Salivary pH and TGF-alpha before and after cisapride administration
      remained unchanged. The stimulatory impact of cisapride on salivary volume and
      inorganic (bicarbonate and nonbicarbonate buffers) and organic (protein,
      glycoconjugate, and EGF) protective components would benefit patients with GERD
      and would also be potential therapy for xerostomia.

PMID- 9246027
TI  - Chest pain at rest in patients with coronary artery disease. Myocardial ischemia,
      esophageal dysfunction, or panic disorder?
AB  - Severe nonexertional (resting) chest pain may be due to myocardial ischemia,
      esophageal dysfunction, psychiatric disorder, or any combination thereof and
      frequently poses a difficult diagnostic challenge. Our aim was to investigate
      causes of chest pain in patients with coronary artery disease. Forty-five
      patients with angiographically proven obstructive coronary lesions and recurrent
      chest pain at rest were studied; 18 had refractory pain despite cardiac therapy
      (problem group), and 27 had documented myocardial ischemia (control group).
      Esophageal manometry, edrophonium provocation, 24-hr pH studies, and psychiatric
      interview were performed in all patients. The clinical evolution and the outcome
      of specific treatment during follow-up was used to establish the etiology of
      chest pain. Esophageal dysfunction was identified in all problem patients and in
      52% of controls, and the esophagus was incriminated as the source of pain in 8
      (44%) and 5 (18.5%), respectively. After a mean follow-up of 49 months (range 24
      76 months), the cause of chest pain in the problem group was identified as panic
      disorder in 9 patients (50%), gastroesophageal reflux in 6 (33%), esophageal
      dysmotility in 2 (11%), and gallstone disease in 1 (6%). Of the control patients,
      18 (67%) had ischemic pain alone, while 9 had concurrent causes: panic disorder
      in 5 (19%) and esophageal dysfunction in 4 (15%). Esophageal dysfunction and
      psychiatric disturbances are common in patients with coronary artery disease
      presenting with resting chest pain, and may contribute to patients' symptoms.

PMID- 9246028
TI  - Gastroesophageal reflux in achalasia. When is reflux really reflux?
AB  - An abnormal score during 24-hr esophageal pH monitoring in achalasia may be
      associated either with a slow steady drift to below pH 4, or else multiple sharp
      dips characteristic of typical gastroesophageal reflux. To test the hypothesis
      that the former pattern was due to food fermentation and not reflux, samples of
      chewed bland food (N = 22) were incubated with saliva at 37 degrees C for 24 hr
      and the pH monitored (in vitro study). Further, the pH tracings of 20 patients
      with achalasia before operation and 12 patients after operation were studied (in
      vivo study). The pH of chewed food fell to a median of pH 4.0 during incubation
      and in seven of 22 samples fell to below pH 4. Preoperatively, four of the five
      patients with an abnormal pH score showed a slow steady drift, and all of these
      had evidence of retained food at endoscopy. Postoperatively, three of the six
      patients with an abnormal pH score had a slow steady drift to below pH 4. Use of
      pH 3 as a threshold clearly distinguished true reflux from food fermentation,
      since the patients with reflux all had an abnormal percentage of time below pH 3.

PMID- 9246030
TI  - Acute ulcer bleeding. A prospective randomized trial to compare Doppler and
      Forrest classifications in endoscopic diagnosis and therapy.
AB  - The aim of our prospective randomized study involving 100 patients was to
      investigate whether Doppler ultrasound can be used to select patients at risk for
      ulcer rebleeding. Ulcers in the Forrest group classified as having a visible
      vessel or a clot were treated prophylactically by injection with epinephrine
      solution. In the Doppler group, in contrast, only ulcers with a positive Doppler
      signal were treated endoscopically. In the Doppler group, rebleeds occurred
      significantly less frequently (2%, P < 0.03) than in the Forrest group (14%).
      Emergency surgery was only necessary in the Forrest group (0% vs 5%; P = 0.02).
      Bleeding-related mortality was 0% and 4% (P = 0.15) and the overall mortality 0%
      and 10% (P = 0.02), in the Doppler and Forrest groups, respectively. These
      results appear to show that Doppler-based injection treatment is superior to
      endoscopic treatment based exclusively on the Forrest classification. In our
      study, Doppler-based local endoscopic treatment reduced the danger of a rebleed
      and thus the number of emergency operations and the overall mortality.

PMID- 9246031
TI  - Gastric mucosal injury induced by local ischemia-reperfusion in rats. Role of
      endogenous endothelin-1 and free radical.
AB  - We investigated the role of an endogenous vasoconstrictor peptide endothelin-1
      (ET-1) and free radicals in local gastric ischemia-reperfusion injury in rats.
      Local gastric ischemia was induced by clamping the left gastric artery for 15 min
      and reperfusion was done for 10-30 min in the presence of 150 mM exogenous HCl
      intragastrically. Local gastric ischemia and reperfusion resulted in significant
      macroscopic and microscopic gastric mucosal damage together with elevation of
      gastric tissue ET-1 concentration. Gastric tissue ET-1 was found to increase
      after 15 min of ischemia alone and also with 30 min of reperfusion. A novel
      nonpeptide endothelin receptor antagonist, bosentan, or a combination of radical
      scavengers (superoxide dismutase, catalase, and deferoxamine) both attenuated
      gastric mucosal injury. However, the greater protection observed with bosentan
      than with radical scavengers might reflect a preferential role of endothelin-1 in
      this type of injury.

PMID- 9246032
TI  - Malondialdehyde and glutathione in rat gastric mucosa and effects of exogenous
      melatonin.

PMID- 9246033
TI  - Helicobacter pylori infection and gastric cancer. A nested case-control study in
      a rural area of Japan.
AB  - We conducted a seroepidemiological nested case-control study to determine the
      association of gastric cancer with Helicobacter pylori infection and atrophic
      gastritis. A cohort of 2858 participants in an annual multiphasic health check-up
      were followed for eight years. Data for 45 gastric cancer cases and 225 sex-, age
      , and address-matched control subjects were analyzed. Helicobacter pylori
      infection was determined by IgG antibodies, and atrophic gastritis was diagnosed
      by both serum pepsinogen I level (< or = 70 ng/ml) and the pepsinogen I/II ratio
      (< or = 3.0). Univariate analysis showed that Helicobacter pylori and atrophic
      gastritis were significantly associated with gastric cancer. In a multivariate
      analysis, atrophic gastritis was associated with significantly increased risk of
      cancer (odds ratio, 3.38; 95% confidence interval, 1.54-7.42); however,
      Helicobacter pylori was not associated with cancer (odds ratio, 1.84; 95%
      confidence interval, 0.59-5.72). These results suggest that Helicobacter pylori
      infection alone is not directly associated with gastric carcinogenesis but has an
      indirect relation to gastric cancer through the development of atrophic
      gastritis.

PMID- 9246034
TI  - Gain of chromosome 20 is a frequent aberration in liver metastasis of colorectal
      cancers.
AB  - To investigate the characteristics of the numerical chromosome aberrations in
      liver metastasis of colorectal cancers, fluorescence in situ hybridization (FISH)
      for chromosomes 8, 18, 14/22, and 20 was performed in 18 specimens of primary
      regions and 18 of metastatic regions in liver metastasis of colorectal cancers
      compared with 15 of non-liver metastatic cancers. Among these numerical
      aberrations, the gain of chromosome 20, especially copy numbers exceeding three,
      was frequently observed in primary and metastatic cancers. Among these numerical
      aberrations, the gain of chromosome 20, especially copy numbers exceeding three,
      was frequently observed in primary and metastatic regions of liver metastasis
      groups compared with that of the non-liver metastasis group (P < 0.05). The
      incidences of gain of chromosome 20 in both regions of the liver metastasis group
      were higher than that of the non-liver metastasis group (P < 0.05). The gain of
      chromosome 20 is a frequent aberration in primary and metastatic regions in
      patients with liver metastatic colorectal cancers and may be available as a
      genetic marker for the diagnosis or prediction of liver metastasis.

PMID- 9246035
TI  - Ammonia inhibits proliferation and cell cycle progression at S-phase in human
      gastric cells.
AB  - Helicobacter pylori (Hp) has strong urease activity and produces a large amount
      of ammonia in the stomach. In animal studies, ammonia was shown to accelerate
      cell kinetics of gastric mucosa, and long-term exposure of the stomach to ammonia
      leads to mucosal atrophy. To understand this process, we examined the effects of
      ammonia on the growth and cell cycle progression of human gastric cancer cell
      lines (HGC-27, MKN1, MKN45) using flow-cytometric analysis. In each cell line,
      ammonia inhibited the cell growth in a dose-dependent manner and caused
      significant accumulation of S-phase cells at a cytostatic dose. DNA synthesis of
      HGC-27 cells treated with ammonia was also suppressed to about 50% of that of the
      untreated cells. Similar effects were observed on addition of ammonium chloride
      at the same concentration, while adjusting the pH of the media with NaOH alone to
      that with the cytostatic dose of ammonia did not affect the cell cycle
      progression. These observations indicate that ammonia induces S-phase arrest in
      gastric cells independently of pH.

PMID- 9246036
TI  - Acute liver failure due to hepatic involvement by hematologic malignancy.
AB  - Infiltration of the liver by secondary malignancies is a rare cause of acute
      liver failure. Acute liver failure caused by malignant infiltration is associated
      with almost 100% mortality and is typically diagnosed postmortem. Richter's
      transformation is a well-recognized complication of chronic lymphocytic leukemia.
      This transformation is the progression of chronic lymphocytic leukemia to a high
      grade lymphoma. We describe the case of a 64-year-old man with a history of
      chronic lymphocytic leukemia who presented with acute liver failure. Liver biopsy
      revealed hepatic infiltration by a high-grade lymphoma. The patient responded to
      chemotherapy with normalization of hepatic function and remained disease-free
      after eight months. This case represents the first report of Richter's
      transformation presenting as acute liver failure. It also represents the fourth
      reported case of a patient with acute liver failure secondary to involvement by a
      hematopoietic malignancy that was successfully recognized and treated.

PMID- 9246037
TI  - Hepatobiliary cystadenocarcinoma without ovarian stroma and normal CA 19-9
      levels. Unusually prolonged evolution.
AB  - Hepatobiliary cystadenoma and cystadenocarcinoma are rare tumors of the liver.
      The differential diagnosis of cystadenoma includes other cystic neoplasms,
      nonneoplastic cysts, and even on some occasions parasitic liver involvement. It
      has been suggested that elevated serum level of the tumor marker CA 19-9 may be
      of value in distinguishing between cystadenoma with ovarian stroma and hydatid
      disease. We report the unique case of a male patient with a hepatobiliary
      cystadenocarcinoma without ovarian stroma of prolonged evolution characterized by
      a normal CA 19-9 serum level, low cyst fluid CA 19-9, and a very weak CA 19-9
      expression on cyst epithelium.

PMID- 9246038
TI  - Potential effect of cyclosporin A in formation of cholesterol gallstones in
      pediatric liver transplant recipients.
AB  - Recent advancements in liver transplantation have resulted in extended survival
      both for grafts and recipients. Such improvement, together with the shortage of
      donor organs has prompted expansion of the donor pool to include less than ideal
      donors, especially in life-threatening situations. The use of older liver donors
      has been associated with lower long-term survival. However, potential morbidity
      such as gallstone formation has not been explored. We analyzed bile composition
      in a child who developed cholesterol gallstones in the proximal bile duct two
      years after undergoing emergency liver transplantation with a liver from a 78
      year-old donor. Oral administration of ursodeoxycholic acid (ursodiol) shifted
      the cholesterol composition of the bile from a supersaturated, potentially
      crystallized state to a liquid (micellar) state. Unlike cyclosporin A, FK506
      showed an increase in the proportion of chenodeoxycholic acid and a decrease in
      the proportion of cholic acid, and thus may exhibit minimal or no hepatotoxic
      effect. Thus, in donor livers with factors known to be associated with
      cholesterol gallstone formation (such as age, sex, or obesity), one may consider
      analyzing the bile composition at the time of procurement. Depending on
      cholesterol and bile acid composition the use of FK506 with or without addition
      of ursodeoxycholic acid may be warranted.

PMID- 9246040
TI  - Depression in patients with cirrhosis. Impact on outcome.
AB  - The impact of depression (assessed by the Beck Depression Inventory) on quality
      of life and outcome was prospectively assessed in adult patients with cirrhosis.
      Patients with depression had significantly poorer perceived quality of life (P =
      0.006), poorer adaptive coping (P = 0.001), and lower functional status, i.e.,
      Karnofsky performance score (P = 0.06), as compared to the nondepressed patients.
      Survival after transplantation was not different between depressed and
      nondepressed patients. However, the patients with depression were significantly
      more likely to die while awaiting transplantation than the nondepressed patients
      (P = 0.02). The difference in mortality between the depressed and the
      nondepressed patients with end-stage liver disease could not be explained by the
      severity of illness variables; Child-Pugh score, complications of liver disease,
      renal function, serum albumin, prothrombin time, frequency and duration of
      hospitalizations were not significantly different for depressed and nondepressed
      patients. Symptoms of depression should be sought in patients with cirrhosis
      since depression is a modifiable illness that is amenable to treatment.

PMID- 9246039
TI  - Enhanced urinary excretion of cGMP in liver cirrhosis. Relationship to
      hemodynamic changes, neurohormonal activation, and urinary sodium excretion.
AB  - Cyclic guanosine monophosphate (cGMP) has been proposed to mediate peripheral
      arterial vasodilation in liver cirrhosis. Nitric oxide and natriuretic peptides
      are the main signals for cGMP generation. Variation in urinary cGMP excretion
      parallels changes in plasma cGMP levels. Our aim was to determine urinary
      excretion of cGMP (UcGMPV) and to investigate its relationship to systemic
      hemodynamics, neurohumoral activity and renal sodium excretion in cirrhosis.
      Urinary excretion of cGMP was measured in 19 healthy subjects and 20 patients
      with alcoholic cirrhosis. Systemic hemodynamic parameters, blood volume (BV),
      plasma atrial natriuretic factor (ANF), and the endothelium-dependent vasodilator
      substance P (SP) were determined in all patients and in five healthy subjects.
      Urinary cGMPV was higher in the group of patients (736 pg/min; 50-3229 pg/min)
      than in controls (126 pg/min; 0-1657 pg/min) (P < 0.01). In addition, UcGMPV
      inversely correlated with the systemic vascular resistance and directly with
      cardiac output, blood volume, SP, ANF, and Pugh's score. By Cox regression
      analysis, only systemic vascular resistance remained inversely associated with
      UcGMPV. In conclusion, urinary cGMP excretion is increased in cirrhosis. It is
      suggested that increased cGMP generation may be related to the hyperkinetic
      circulation in human cirrhosis.

PMID- 9246041
TI  - Liver involvement in obese children. Ultrasonography and liver enzyme levels at
      diagnosis and during follow-up in an Italian population.
AB  - Our aim was to evaluate incidence and risk factors of liver involvement in obese
      Italian children as assessed by both ultrasonographic and biochemical parameters.
      In seventy-five consecutive obese children (age 9.5 +/- 2.9 years, males/females
      41/34), serum levels of enzymes and ultrasonography of the liver were evaluated.
      Tests were repeated one, three, and six months after starting a moderate
      hypocaloric diet and an exercise program. Three obese children who were found to
      have chronic viral hepatitis were excluded from the study. Thirty-eight of 72
      (53%) obese children had an ultrasonographic image of bright liver consistent
      with liver steatosis. The latter was severe in nine children, moderate in 16, and
      mild in 13. Eighteen obese children (25%) had elevated transaminase levels.
      Bright liver and hypertransaminasemia were not due to any of the most common
      causes of liver disease. Both were rapidly responsive to loss of weight,
      confirming that liver involvement was secondary to obesity and that steatosis or
      steatohepatitis rather than fibrosis were involved. Obesity duration not more
      than three years (odds ratio = 4.77), a higher degree of obesity (odds ratio =
      2.09), and hypertransaminasemia (odds ratio = 2.15) appeared as important
      predictive factors of liver involvement at ultrasonography. Incidence of liver
      involvement assessed by means of ultrasonography is significantly higher than
      that revealed by measurement of serum liver enzymes. A short duration of obesity
      emerged as a potentially new risk factor of liver involvement in the pediatric
      obese population and needs to be confirmed in future studies.

PMID- 9246042
TI  - Methimazole slows hepatocyte streaming in rats.
AB  - Hepatocytes are hypothesized to continually stream from the portal tract to the
      terminal hepatic vein. By this model, when a cell divides, one of its progeny
      replaces the dividing ancestor and the other is displaced into a more remote
      location. The present experiment aims to demonstrate that hypothyroidism affects
      liver cell turnover. Thirty male adult rats were divided into two groups. One
      received methimazole for two weeks and the other served as control. Each rat was
      injected intraperitoneally with 18.5 KBq [3H]thymidine/g body weight. Rats were
      killed after 1 hr and two and four weeks. Autoradiography was done. The distance
      of the labeled cells from the portal tract was measured. The mean TSH levels of
      the methimazole-treated group and controls were 1.45 and 0.25 mM/liter,
      respectively (P < 0.01). Hepatocyte streaming was lower in hypothyroid (1.8
      microns/day) than in untreated rats (2.5 microns/day) (P < 0.01). The respective
      labeling indices 1 hr after labeling were 0.9% and 1.24% (P < 0.05). We conclude
      that hypothyroidism diminishes hepatocyte and littoral cell turnover and slows
      down their streaming.

PMID- 9246044
TI  - Granulomatous hepatitis in a patient with chronic hepatitis C treated with
      interferon-alpha.
AB  - Common adverse effects of IFN-alpha include flulike symptoms, headache,
      irritability, and bone marrow suppression. Hepatic side effects are unusual
      except in patients with pretreatment autoimmune hepatitis. Granuloma formation in
      the liver as a result of IFN-alpha therapy has never been reported. We described
      a 48-year-old female with chronic hepatitis C infection who developed
      granulomatous hepatitis following treatment with IFN-alpha. The granulomatous
      inflammation resolved after discontinuation of IFN-alpha treatment. Possible
      mechanisms for this unusual occurrence are discussed.

PMID- 9246043
TI  - Long-term efficacy of interferon-alpha and ursodeoxycholic acid in treatment of
      chronic type C hepatitis.
AB  - Interferon-alpha (IFN) and ursodeoxycholic acid (UDCA) combined have a
      controversial role in the treatment of chronic type C hepatitis. We studied the
      long-term efficacy of both drugs alone or in combination. In a three-year period,
      108 patients were randomized into three treatment arms: (1) IFN alone 3 MU three
      times a week (N = 49), (2) IFN 3 MU three times a week + UDCA 250 mg twice a day
      (N = 45), and (3) UDCA alone 250 mg twice a day (N = 14). Response was defined as
      complete normalization of serum ALT. For the responders at the end of six months,
      the treatment was run to 12 months. Nonresponders (NRs) of the first group were
      crossed over to combination and NRs of the combination received 6 MU three times
      a week IFN+UDCA for the next six months. The enrollment to the UDCA alone arm was
      stopped early, since only 1/14 normalized serum ALT at the end of third month.
      However, 12/14 completed six months and 11 NRs received IFN 3 MU three times a
      week alone for the next six months. Twelve discontinued treatment due to side
      effects. Responders were followed-up untreated for 18 months. Sustained response
      (SR) was defined as persistence of normal serum ALT levels in this period. At the
      end of six months, 22/45 (48%) from the IFN-alone and 23/39 (58%) from the
      combination group responded. Twenty NRs from former and 15 of latter group were
      crossed over. While none of the 20 from the IFN-alone group responded to the
      combination, 1/15 NRs of the combination group responded to dose escalation. SR
      was achieved in 9/45 (20%) of the IFN alone and 7/39 (18%) of the combination
      group. The mean time form the end of the treatment to the relapse was not
      different between the groups. Five of 11 UDCA NRs responded to IFN with SR in 2.
      It was concluded that UDCA as a single agent is ineffective in achieving response
      in the treatment of chronic type C hepatitis. Combined with IFN, it increases
      response rate insignificantly although this is not sustained.

PMID- 9246045
TI  - Sclerotherapy in noncirrhotic portal fibrosis.
AB  - Endoscopic sclerotherapy has emerged as an effective and safe mode of treatment
      for long-term management of esophageal varices due to cirrhosis of liver and
      extrahepatic portal venous obstruction. There are few studies that have evaluated
      the role of sclerotherapy in the management of esophageal varices in patients
      with noncirrhotic portal fibrosis (NCPF). We report our results of long-term
      sclerotherapy in patients with NCPF. Seventy-two consecutive patients (men 29,
      women 43; age 32.9 +/- 11.8 years) with recurrent variceal bleeding due to NCPF
      were entered into the sclerotherapy program. Forty-eight patients received
      intravariceal absolute alcohol and 24 patients received intravariceal sodium
      tetradecyl sulfate (STD). Variceal obliteration was achieved in 65 (90.3%)
      patients with a mean of 5.7 +/- 3.0 (range 1-14) sessions. These patients were
      followed-up for a mean of 21.4 +/- 20.4 (range 1-96) months. Thirteen (17.3%)
      patients had episodes of upper gastrointestinal bleeding during sclerotherapy.
      Rebleed after obliteration was seen in 6 (9.2%) patients. Sclerotherapy was
      associated with a significant reduction in bleeding rate (bleeds per month per
      patient) during sclerotherapy and after obliteration of varices as compared to
      presclerotherapy period (P < 0.000001 for both). Recurrence of esophageal varices
      after obliteration was seen in 9 (13.9%) patients with reobliteration of varices
      in five patients in whom sclerotherapy was attempted. Complications including
      esophageal ulcer and stricture formation were seen in 18 (25%) and 4 (5.6%)
      patients respectively; strictures were restricted to patients who received
      absolute alcohol. Two (2.77%) patients died of massive upper gastrointestinal
      bleed during follow-up. We conclude that sclerotherapy is an effective and safe
      modality in the prevention of variceal bleeds in patients with NCPF.

PMID- 9246046
TI  - Use of oral GoLytely solution in relief of refractory fecal impaction.
AB  - Constipation and fecal impaction are common disorders with multiple treatment
      options. We describe the use of GoLytely oral solution in 10 patients admitted to
      a community hospital and referred to a single gastroenterologist for fecal
      impaction refractory to conventional medical treatment. Seven women and three men
      received enemas, bisacodyl suppositories, and digital fragmentation either solely
      or in combination prior to the administration of GoLytely oral solution. The
      patients had no clinical and radiological evidence of bowel obstruction. All had
      underlying cardiovascular problems. Their mean age was 78.1 years (range 49-100
      years). GoLytely oral solution (Braintree Laboratories, Inc.) was administered at
      a rate of 100 ml/hr per orem to three patients, via nasogastric tube in six
      patients, and via gastrostomy tube in one patient. All 10 patients were able to
      regularly pass feces and show radiographical colorectal clearing within 6.0 to
      57.25 hr (mean 23.60 hr). No significant complications were observed. Eight
      patients were discharged from the hospital within 24 hr of termination of
      treatment while two patients remained for unrelated medical conditions. GoLytely
      oral solution effectively relieved fecal impaction in 10 patients refractory to
      conventional medical treatment.

PMID- 9246047
TI  - Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune
      pancreatitis with effective steroid therapy.
AB  - The most common forms of chronic pancreatitis are related to alcohol ingestion,
      whereas the entity of non-alcohol-associated (idiopathic) pancreatitis is poorly
      understood. Autoimmunity has been suggested as a possible etiologic factor of
      idiopathic chronic pancreatitis. A total of 362 Japanese patients underwent
      endoscopic retrograde pancreatography (ERP) for suspected pancreatic disease, and
      161 were diagnosed with chronic pancreatitis. Among them, we found three cases
      (1.86% incidence) of unique chronic pancreatitis, in which ERP revealed diffuse
      narrowing of the main pancreatic duct with an irregular wall. We diagnosed these
      three patients as having pancreatitis associated with an autoimmune mechanism
      morphologically and biochemically and started them on steroid therapy. The
      characteristics of the these three patients were as follows:
      hypergammaglobulinemia, eosinophilia, ultrasonography showing hypoehoic diffuse
      swelling in the pancreas (sausage-like appearance), ERP showing diffuse narrowing
      of the main pancreatic duct with irregular like thumbprint-like marks, reversible
      exocrine insufficiency, and positive anti-carbonic anhydrase II antibody. After
      one month of the treatment with steroids, pancreatitis dramatically improved
      morphologically and enzymatically. Here we describe these cases of the suspected
      autoimmune chronic pancreatitis. We must recognize the concept and the features
      of autoimmune pancreatitis in order to avoid unnecessary surgery as pancreatic
      cancer.

PMID- 9246048
TI  - Serum interleukin-10 in human acute pancreatitis.
AB  - Interleukin 10 (IL-10) recently emerged as an antiinflammatory cytokine that
      inhibits the secretion of proinflammatory cytokines by monocytes and/or
      macrophages and the release of free oxygen radicals. It has been reported that
      treatment with IL-10 decreases the severity of experimental pancreatitis, mainly
      by inhibiting cellular necrosis. The aim of this study was to evaluate the
      behavior of serum IL-10 in patients with acute pancreatitis and to explore the
      possibility of a relationship between this cytokine and severity of the disease.
      Forty-five patients with acute pancreatitis were studied. Acute pancreatitis was
      of biliary origin in 30 patients, due to alcohol abuse in 10, due to pancreas
      divisum in 1, and of unknown origin in the remaining 4. According to the
      Balthazar criteria, 19 patients had scores of A, B, or C and 25 had scores of D
      or E. Twelve healthy subjects were also studied as controls. Serum IL-10 was
      determined in all subjects on admission, and in acute pancreatitis patients also
      daily for the following four days using a commercial kit. Healthy subjects had no
      detectable serum levels of IL-10. In acute pancreatitis patients, serum IL-10
      levels were increased on the first day of the disease and then progressively
      decrease in the following days. On the first day of the acute pancreatitis,
      patients with the mild disease had serum levels of IL-10 significantly higher
      than those with severe disease, whereas in the following days, no statistically
      significant difference was observed between the two groups. The elevation of IL
      10 on the first day of the illness is more marked in patients with mild acute
      pancreatitis than in those with the severe form of the disease. The finding of
      low values of serum IL-10 in severe acute pancreatitis suggests that there may be
      altered down-regulation of the immune system response in these patients.

PMID- 9246049
TI  - Differential induction of HSP60 and HSP72 by different stress situations in rats.
      Correlation with cerulein-induced pancreatitis.
AB  - We previously reported that water-immersion stress specifically induced the
      synthesis of a 60-kDa heat-shock protein (HSP60, chaperonin homolog) in
      pancreatic cells and preinduction of HSP60 completely prevented development of
      cerulein-induced pancreatitis in the rat in an HSP60 quantitatively dependent
      manner. In order to study the cytoprotective function of a 72-kDa heat-shock
      protein (HSP72, stress-inducible hsp70), the effect of specific preinduction of
      HSP72 by hyperthermia on cerulein-induced pancreatitis was investigated and
      compared with the effect of preinduction of HSP60 in this study. Expression of
      HSP60 and HSP72 in the pancreas was investigated by immunoblot before and after
      water immersion or hyperthermia. Following pretreatment with water-immersion
      stress or hyperthermia, the rats were injected with cerulein (40 micrograms/kg,
      intraperitoneally). The pancreas wet weight and serum amylase concentration were
      measured before and after cerulein injection. Hyperthermia (42.5 degrees C, 20
      min) specifically induced HSP72 in the pancreas. The synthesis of HSP60 was
      specifically induced by water-immersion stress in the pancreas. Cerulein-induced
      pancreatitis was clearly prevented by specific preinduction of HSP60 by water
      immersion stress. However, preinduction of HSP72 by hyperthermia had no
      preventive effect on cerulein-induced pancreatitis. Our findings suggest that
      HSP60 and HSP72 have distinct functions in the pancreas, and their induction
      mechanisms are also different in vivo. These results could be important for
      understanding the mechanism of "adaptive cytoprotection" in the pancreas mediated
      by heat-shock proteins.

PMID- 9246050
TI  - Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no
      evidence of multiple endocrine neoplasia type 1.
AB  - The characteristic features of a 48-year-old male presenting with isolated
      acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no
      relation to MEN1 was reported. The clinical features, laboratory findings, and
      sellar enlargement were improved after removal of the pancreatic tumor. The
      resected pancreatic tumor showed positive GRH immunoreactivity and contained
      abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have
      been reported. In the management of acromegaly, the measurement of GRH is
      recommended and the search for an ectopic source will prevent unnecessary and
      potentially ineffective pituitary surgery.

PMID- 9246051
TI  - Terbinafine-induced prolonged cholestasis with reduction of interlobular bile
      ducts.
AB  - The antifungal drug terbinafine has infrequently been incriminated in the
      occurrence of acute liver injury. We report a case of prolonged cholestasis that
      occurred in a 75-year-old woman, following terbinafine administration. Jaundice
      followed by pruritus appeared after four weeks of therapy and was associated with
      mixed hepatocellular and cholestatic liver tests abnormalities. Following drug
      withdrawal, serum bilirubin returned to normal values within three months, but
      anicteric cholestasis persisted for over six months. A liver biopsy performed
      after six months showed centrilobular cholestasis, discrete portal fibrosis, and
      a reduction in the number of interlobular biliary ducts. Terbinafine should be
      added to the list of drugs that can cause reduction in interlobular bile ducts.

PMID- 9246052
TI  - Neurogenic inflammation in cholecystitis.
AB  - Neurogenic inflammation implies stimulation of nerves with resultant inflammation
      in tissue surrounding the nerve terminals. We hypothesized that neurogenic
      inflammation has a role in cholecystitis. Capsaicin (stimulant of afferent,
      nociceptive neurons), 6-hydroxydopamine (stimulates release of peptides from
      sympathetic nerve terminals), bradykinin, lipopolysaccharide, and saline were
      instilled into guinea pig gallbladders for 24 hr (N = 5 in each group). In
      parallel, test agents were instilled with 1% Iidocaine. Water transport across
      gallbladder mucosa, myeloperoxidase and interluekin-1 release from gallbladder
      tissue, and prostaglandin E2 in luminal fluid were measured. Capsaicin caused
      water secretion and significant release of myeloperoxidase, interleukin-1, and
      prostaglandin-E2, effects that were blocked by Iidocaine. 6-Hydroxydopamine did
      not affect water transport or prostaglandin E2, but did cause myeloperoxidase and
      interleukin-1 release. Bradykinin- and lipopolysaccharide-induced inflammation
      were partially inhibited by lidocaine. Taken together, these results suggest that
      neurogenic inflammation has a role in the pathophysiology of cholecystitis.

PMID- 9246053
TI  - Effect of endoscopic sphincterotomy on gallbladder motility.
AB  - In experimental animals, sphincterotomy facilitates passage of solids from the
      gallbladder and inhibits gallstone formation apparently by improvement in
      gallbladder emptying. In humans, however, gallbladder emptying has not been
      studied following endoscopic sphincterotomy (ES) in patients with gallstones. We
      therefore prospectively studied resting and cerulin-stimulated gallbladder
      volumes by real time ultrasonography in 15 patients of choledocholithiasis with
      gallbladder in situ (eight with and seven without gallbladder calculi) before and
      after (after bile duct clearance) ES. ES significantly lowered resting
      gallbladder volume (21.2 +/- 10.6 vs 11.1 +/- 5.0; P < 0.0001) and cerulin
      stimulated residual gallbladder volume (10.8 +/- 5.6 vs 4.4 +/- 2.1; P < 0.0001).
      ES also significantly increased the gallbladder ejection fraction (47.3 +/- 12.1%
      vs 58.8 +/- 11.1%; P < 0.0001). The rate constant for gallbladder emptying after
      cerulin infusion also increased significantly after ES (-0.022/min vs -0.031/
      min; P < 0.0001). Significant improvement in gallbladder motility was observed in
      both groups of patients with and without gallbladder calculi. ES significantly
      improves gallbladder motility in humans.

PMID- 9246054
TI  - Discordance of pressure recordings from biliary and pancreatic duct segments in
      patients with suspected sphincter of Oddi dysfunction.
AB  - It remains controversial whether manometric parameters recorded from the
      pancreatic and biliary segment of the sphincter of Oddi (SO) differ. We therefore
      studied 48 consecutive patients (40 women, 43 +/- 11 years) with suspected SO
      dysfunction, in 33 of whom successful dual-duct SO manometry was obtained.
      Measures of concordance between the two duct segments were moderate for basal
      sphincter pressure (K = 0.31) and for contractile frequency (0.35), and were low
      for peak pressure (0.15) and for proportion of retrograde propagation (-0.19).
      There was also low concordance (-0.13) for the overall manometric diagnosis, and
      in 48% (CI 31-66%) of patients a conflicting diagnosis (normal/abnormal) was
      obtained from the two ducts. There was no evidence of a differential motor effect
      of CCK on either duct, nor were there significant differences in the rate of
      manometric abnormality according to the order of initial duct cannulation. These
      results indicate that, if technically feasible, dual-duct manometry of the
      sphincter of Oddi is required for diagnostic precision.

PMID- 9246055
TI  - Small bowel dysmotility in patients with postcholecystectomy sphincter of Oddi
      dysfunction.
AB  - Postcholecystectomy patients (N = 27) with severe recurrent biliary-like pain who
      had no evidence of organic disease were subdivided into those with and those
      without objective evidence of sphincter of Oddi dysfunction (SOD) based on two
      separate criteria: (1) clinical criteria-elevated liver function tests and/or
      amylase with pain, and/or a dilated bile duct, and/or delayed drainage at ERCP (N
      = 14, SOD classes I and II); and (2) abnormal biliary manometry (N = 19).
      Prolonged (24-48 hr) ambulant recording of duodenojejunal motor activity was
      performed in all patients and interdigestive small bowel motor activity compared
      between patient subgroups and a healthy control group. Phase II motor abnormality
      was more frequent in patients with, compared to those without, objective clinical
      criteria of SOD (7/14 vs 0/13, P = 0.003). Phase III abnormality also tended to
      be more frequent in these patients (7/14 vs 2/13, P = 0.06). In addition, both
      phase III (P = 0.03) and phase II (P = 0.03) motility index (MI) was higher in
      patients with sphincter dyskinesia compared to controls; phase II MI was also
      higher in patients with sphincter stenosis (P = 0.005). Disturbances of small
      bowel interdigestive motor activity are more prevalent in postcholecystectomy
      patients with, compared to those without, objective evidence of SOD, and
      especially in patients with SO dyskinesia. Postcholecystectomy SOD in some
      patients may thus represent a component of a more generalized intestinal motor
      disorder.

PMID- 9246057
TI  - Effect of solid and liquid diet on uptake of large particulates across intestinal
      epithelium in rats.
AB  - The effect of diet composition on the uptake of particulates across the
      gastrointestinal epithelium has been examined in fasted male weanling Sprague
      Dawley rats by estimating the systemic uptake of orally administered 2-microns
      latex polystyrene microspheres. Using a tissue solubilization assay, particle
      transfer in animals maintained on a fluid diet was determined. A larger number of
      particles was transferred from the gut lumen to the internal organs, including
      the mesenteric lymph node, spleen, bone marrow, liver, kidney, and heart of
      animals fed solid pelleted diet than those maintained on a fluid-diet 4 hr after
      oral administration of particles. The increase in particle number in rats fed the
      solid diet was only statistically significant (P < 0.05) for brain tissue in the
      analysis for trend. However, the number of particles retained in the proximal
      region of the gut at the end of this period was greater in animals fed the fluid
      diet. This work demonstrates that diet composition is important in
      gastrointestinal transepithelial translocation of microspheres.

PMID- 9246056
TI  - Obstructive ileus of large bowel is associated with low tissue levels of
      neuropeptides in prestenotic bowel segment.
AB  - The neuropeptides substance P, vasoactive intestinal polypeptide, and the
      recently discovered peptide secretoneurin are neurotransmitters of the intrinsic
      nervous system of the gut and effect gut motility. The aim of this study was to
      investigate whether these neuropeptides are involved in the pathophysiology of
      large bowel ileus. Five patients underwent colonic resections for obstructive
      cancer of the colon. Full-thickness specimens of the resected colon were taken 10
      cm proximal and 10 cm distal to the site of tumor obstruction. Substance P-,
      vasoactive intestinal polypeptide-, and secretoneurin-like immunoreactivities
      were measured in the specimens by radioimmunoassay. In addition
      immunocytochemistry was performed. Tissue levels of substance P, vasoactive
      intestinal polypeptide, and secretoneurin were lower in the prestenotic than in
      the poststenotic bowel segment. In accordance, immunocytochemistry revealed a
      denser staining of ganglion cells and fibers for all three neuropeptides in the
      poststenotic bowel. The decreased tissue levels of substance P, vasoactive
      intestinal polypeptide, and secretoneurin in the prestenotic bowel segment may
      contribute to the final decompensation of obstructive ileus.

PMID- 9246058
TI  - Tachykinins stimulate lipid peroxidation mediated by free radicals in
      gastrointestinal tract of rat.
AB  - Tissue concentrations of malondialdehyde in the gastrointestinal tract of the rat
      were quantified as indicators of lipid peroxidation and tissue damage after
      challenge with tachykinins and after pretreatment with allopurinol. Neurokinin A,
      neurokinin B, and substance P given intravenously during 30 min increased the
      production of malondialdehyde in the stomach, duodenum, jejunum, and colon in a
      dose-dependent manner at doses from 100 to 400 pmol/kg/min (P < 0.05-0.01).
      However, the stomach seemed less responsive to the tachykinin challenge. For
      comparison, a similar dose-dependent increase of malondialdehyde was found in the
      liver and lung, with more pronounced effects of neurokinin B (P < 0.05-0.01).
      Pretreatment with allopurinol, 10 mg/kg, significantly reduced malondialdehyde
      responses to tachykinin challenge in intestinal tissues (P < 0.001). In
      conclusion, elaboration of malondialdehyde is suggested to reflect the ability of
      gastrointestinal tissues to react to tachykinins at high concentrations with
      liberation of free radicals as part of an inflammatory reaction.

PMID- 9246059
TI  - Dietary supplementation of nucleotides and arginine promotes healing of small
      bowel ulcers in experimental ulcerative ileitis.
AB  - We previously showed that intravenous total parenteral nutrition supplemented
      with nucleosides and nucleotides (NS/NT) promoted ulcer healing in rats with
      indomethacin-induced ileitis. The present study evaluated whether dietary NT
      supplementation would similarly affect ulcer healing in this model. Female Lewis
      rats were randomized into either control or experimental groups receiving yeast
      RNA containing NT or arginine, glutamine, fish oil, guar gum, or a combination of
      yeast RNA+arginine diets. Ileitis was induced by two doses of indomethacin (7.5
      mg/kg) administered subcutaneously 24 hr apart. Ulcer number and length were
      determined at 4, 8, and 14 days after induction of ileitis. Ileal villous and
      crypt length, crypt-villous ratio, and bromodeoxyuridine (BrdU) labeling were
      studied in the control and yeast RNA-supplemented diet groups. Ileal ulceration
      was present in all groups at 4 and 8 days and was almost healed by 14 days. Rats
      receiving yeast RNA, arginine, and yeast RNA + arginine diets showed a
      significant decrease in ulcer number (56%, 28%, and 34%, respectively) and length
      (67%, 41%, and 48%, respectively) compared to controls at 8 but not at 4 days.
      Glutamine, fish oil, and guar gum had no effect on ulcer healing at 4, 8, or 14
      days. Among the histological parameters, a significant decrease in crypt length
      in the yeast RNA-supplemented group at 8 days suggested an acceleration of the
      healing process and restoration to a near-normal crypt-villous architecture. We
      conclude that the yeast RNA, arginine, and yeast RNA + arginine diets accelerated
      ulcer healing, as indicated by decreased ulcer number and length. We postulate
      that the underlying mechanism(s) contributing to ulcer healing may be related, in
      part, to increased cell proliferation.

PMID- 9246060
TI  - Spectrum of ischemic colitis in cocaine users.
AB  - Ischemic enterocolitis is a well-recognized entity occurring in cocaine users.
      Diagnosis is based on the presence of rectal bleeding, abdominal pain, a history
      of cocaine use, supportive endoscopic and histopathologic findings, and the
      absence of other etiologic mechanisms of ischemic colitis. In this study, we
      evaluated endoscopic and histopathologic findings in seven patients with cocaine
      colitis. Lesions seen by endoscopy, which were restricted to the left colon,
      included hemorrhagic edematous mucosa, pseudopolyps, and ulcerations. Rectal
      involvement, not a common feature of ischemic colitis, was seen in five patients.
      In two patients histologic lesions were classified acute/subacute, and in three
      patients as subacute/chronic. In the remaining two patients lesions were combined
      acute/subacute and chronic. The presence of subacute/chronic lesions suggested
      recurrent ischemic episodes and could reflect repeated use of cocaine. Future
      studies will be needed to define the long-term clinical and histopathologic
      significance of these subacute/chronic lesions.

PMID- 9246061
TI  - Interleukin-2 fusion protein (DAB389IL-2) selectively targets activated human
      peripheral blood and lamina propria lymphocytes.
AB  - Activated mucosal T lymphocytes correlate with the intestinal inflammation of
      inflammatory bowel disease. Activated T cells elaborate interferon-gamma (IFN
      gamma) and express high-affinity interleukin-2 (IL-2) receptors. The IL
      2/diphtheria toxin fusion protein (DAB389IL-2) has been shown to specifically
      kill high affinity IL-2 receptor-bearing cells. We tested whether DAB389IL-2
      could specifically target activated lamina propria lymphocytes. Lymphocytes were
      activated in vitro with phytohemagglutinin and IL-2 for 24-48 hr. Toxin efficacy
      was determined by the [14C]leucine incorporation, IFN-gamma ELISA, and flow
      cytometry. DAB389IL-2 (10(-11) M) inhibited protein synthesis by 80% in activated
      lamina propria lymphocytes. This inhibition was blocked by coculture of either
      excess IL-2 or a nonfunctional IL-2 diphtheria toxin mutant protein. DAB389IL-2
      (10(-12) M) also significantly reduced the numbers of activated helper T cells
      and IFN-gamma levels in 24-hr cultures. DAB389IL-2 specifically targets activated
      IL-2 receptor-positive lamina propria lymphocytes and is a potential new
      therapeutic agent for patients with active inflammatory bowel disease.

PMID- 9246062
TI  - 99mTc-HMPAO granulocyte scintigraphy in the early detection of postoperative
      asymptomatic recurrence in Crohn's disease.
AB  - The usefulness of 99mTc-HMPAO scintigraphy in the early detection of
      postoperative recurrence of Crohn's disease was evaluated in 17 patients
      undergoing ileocecal resection and prospectively followed up for one year.
      Scintigraphy was performed 6 and 12 months after surgery and recurrence assessed
      by colonoscopy within two weeks. As controls, four patients with ileocecal
      resection for cecal carcinoma were studied. To perform scintigraphy, autologous
      granulocytes were labeled with 99mTc-HMPAO, injected, and tau-camera images
      acquired after 30 min and 3 hr. Six months after surgery, 4/8 Crohn's disease
      patients showed endoscopic recurrence, and 30-min scintigraphy was positive only
      in these four patients (four true positives, four true negatives). At 12 months,
      endoscopic recurrence was detected in 10/14 Crohn's disease patients, and 30-min
      scintigraphy was positive in 9/14 patients (eight true positives, three true
      negatives, two false negatives, one false positive). Scintigraphy at 3 hr showed
      a lower specificity in detecting CD recurrence both at 6 and 12 months. The
      endoscopic and 30-min scintigraphic score were significantly correlated both at 6
      and 12 months (P = 0.007; P = 0.04). Scintigraphy was negative in 4/4 controls at
      30 min (four true negatives) and positive in 1/4 (one false positive) at 3 hr. We
      conclude that 99mTc-HMPAO scintigraphy at 30 min is a sensitive technique for the
      early detection of Crohn's disease recurrence in patients under regular follow-up
      after surgery.

PMID- 9246064
TI  - Role of appendectomy and tonsillectomy in pathogenesis of ulcerative colitis.
AB  - We wished to determine the effect of appendectomy and tonsillectomy on the
      subsequent risk for development of ulcerative colitis (UC). We conducted a case
      control study at the University of Oklahoma Hospital and VA Medical Center
      gastroenterology clinics, as well as at the offices of private physicians.
      Subjects being followed for UC formed the study group. Patients being followed at
      Internal Medicine Associates of the University of Oklahoma clinics formed the
      controls. We recorded the patient's name, age, sex, race, history of smoking, and
      history of appendectomy or tonsillectomy. The study group consisted of 193
      patients, and there were 394 controls. The prevalence of appendectomy was lower
      (17.8% vs 5.2%) among patients with UC (P < 0.01). The prevalence of
      tonsillectomy was similar in the two groups (20.6% vs 18.1%; P = NS). We conclude
      that appendectomy is associated with a decreased risk for subsequent development
      of ulcerative colitis.

PMID- 9246063
TI  - Quantitative PCR analysis of TNF-alpha and IL-1 beta mRNA levels in pediatric IBD
      mucosal biopsies.
AB  - Inflammatory bowel disease (IBD) is associated with increased activation of
      intestinal immune cells, whose overproduction of proinflammatory cytokines such
      as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) is
      implicated in mediating the sustained inflammatory response. Studies to date have
      largely reported qualitative differences in cytokine gene expression between IBD
      and controls. Our aim was to perform quantitative analysis of intestinal mucosal
      mRNA expression in colonic biopsies from pediatric IBD patients using a
      competitive polymerase chain reaction. IL-1 beta and TNF-alpha were expressed in
      all IBD and control biopsies. Compared to controls, IL-1 beta mRNA levels were
      increased in involved tissue from Crohn's disease (CD) patients, but not in
      histologically uninvolved CD or in ulcerative colitis (UC) mucosa. IL-1 beta
      expression in the latter groups were equivalent to those found in tissue from
      patients with eosinophilic colitis (EOC). Significantly higher levels of IL-1
      beta mRNA were found in uninvolved mucosa from CD patients who presented with a
      relapse of disease activity, as compared to newly diagnosed cases with
      histological features of CD at an early stage. TNF-alpha mRNA transcripts were
      also significantly elevated in involved CD mucosa, but not in the other groups.
      TNF-alpha gene expression in CD-involved tissue decreased with disease duration.
      Follow-up of the patients revealed that high cytokine expression in uninvolved CD
      tissue correlated with an early clinical relapse. In conclusion, quantitative
      determination of proinflammatory cytokine gene expression reveals differences
      between the type, severity, and clinical course in patients with IBD.

PMID- 9246065
TI  - Activation of a distributed somatosensory cortical network in the human brain. A
      dipole modelling study of magnetic fields evoked by median nerve stimulation.
      Part I: Location and activation timing of SEF sources.
AB  - Cortical areas responsive to somatosensory inputs were assessed by recording
      somatosensory evoked magnetic fields (SEF) to electrical stimulation of the left
      median nerve at wrist, using a 122-SQUID neuromagnetometer in various conditions
      of stimulus rate, attentional demand and detection task. Source modelling
      combined with magnetic resonance imaging (MRI) allowed localisation of six SEF
      sources on the outer aspect of the hemispheres located respectively: (1) in the
      posterior bank of the rolandic fissure (area SI), the upper bank of the sylvian
      fissure (parietal opercular area SII) and the banks of the intraparietal fissure
      contralateral to stimulation, (2) in the SII area ipsilateral to stimulation and
      (3) in the mid-frontal or inferior frontal gyri on both sides. All source areas
      were found to be simultaneously active at 70-140 ms after the stimulus, the SI
      source was the only one active already at 20-60 ms. The observed activation
      timing suggests that somatosensory input from SI is processed to higher-order
      areas through serial feedforward projections. However the long-lasting
      activations of all sources and their overlap in time is also compatible with a
      top-down control mediated via backward projections.

PMID- 9246066
TI  - Activation of a distributed somatosensory cortical network in the human brain: a
      dipole modelling study of magnetic fields evoked by median nerve stimulation.
      Part II: Effects of stimulus rate, attention and stimulus detection.
AB  - In this study we used a repeated measures design and univariate analysis of
      variance to study the respective effects of ISI, spatial attention and stimulus
      detection on the strengths of the sources previously identified by modelling SEFs
      during the 200 ms following mentally counted left median nerve stimuli delivered
      at long and random ISIs (Part I). We compared the SEF source strengths in
      response to frequent and rare stimuli, both in detection and ignoring conditions.
      This permitted us to establish a hierarchy in the effects of ISI, attention and
      stimulus detection on the activation of the cortical network of SEF sources
      distributed in SI and posterior parietal cortex contralateral to stimulation, and
      in the parietal operculum (SII) and premotor frontal cortex of both hemispheres.
      In all experimental conditions the SI and parietal opercular sources were the
      most active. All sources were more active in response to stimuli delivered at
      long and random ISIs and the frontal sources were activated only in this
      condition of stimulation. Driving the subject's attention toward the side
      stimulated had no detectable effect on the activity of SEF sources at short ISI.
      At long ISIs mental counting of the stimuli increased the responses of all
      sources except SI. These results suggest that activation of frontal sources
      during mental counting could reflect a working memory process, and that of
      posterior parietal sources a spatial attention effect detectable only at long
      ISIs.

PMID- 9246067
TI  - Detailed analysis of the latencies of median nerve somatosensory evoked potential
      components, 2: Analysis of subcomponents of the P13/14 and N20 potentials.
AB  - Detailed analysis of P13/14 and N20 wavelets was performed for 62 normal subjects
      and patients with various lesions along the somatosensory pathway. A histogram of
      the latencies of all the identified P13/14 wavelets (measured from P13/14 onset)
      demonstrated three latency-groups, which were named P13, P14a and P14b
      subcomponents. The relationship between the three newly identified subcomponents
      and the conventional naming of P13 and P14 was inconstant, indicating the
      ambiguity of the latter. P14b was most prominent in the contralateral central
      region, and therefore a P15 positivity slightly after P14b was often recorded in
      the CPc-Fz and CPc-CPi leads (CPc and CPi are centroparietal electrodes
      contralateral and ipsilateral to the stimulation). P14b/P15 was lost even in
      patients with cortical lesions, and thalamocortical fibers were assumed for its
      origin. The CPc-Fz and CPi-Fz leads registered a low negativity named broad N13',
      suggesting frontal predominance of the overall P13/14 complex. Both P13 and P14a
      were identified in a patient with a pontine lesion, and a caudal brainstem origin
      for both was suspected due to the onset of two repetitive bursts of the ascending
      lemniscal volley. We refuted the presynaptic origin of the scalp P13 potential
      and pointed out that a prolonged and/or polyphasic P11 frequently observed in
      patients with high cervical lesions can be mistaken as scalp P13. A histogram of
      the latencies of all the identified negative wavelets of N20 in the CPc-Fz lead
      (measured from N20 onset) revealed five definite latency-groups, which were named
      N20a, N20b, N20c, N20d and N20e subcomponents. The highest peak of N20 actually
      corresponded to either N20b, N20c or N20d, and this uncertainty, which must be
      related to intracortical processes, resulted in a large instability of the N20
      peak latency as well as the age and sex dependence of the N20 onset-peak
      interval, both of which were demonstrated by our preceding study (Sonoo, M.,
      Kobayashi, M., Genba-Shimizu, K., Mannen, T. and Shimizu, T. Detailed analysis of
      the latencies of median nerve SEP components, 1: selection of the best standard
      parameters and the establishment of the normal values. Electroenceph. clin.
      Neurophysiol., 1996b, 100: 319-331). Negative subcomponents in the CPc-NC lead
      and positive subcomponents in the Fz-NC lead constituted mirror images of each
      other, which suggested that these subcomponents were generated within area 3b.

PMID- 9246068
TI  - Selective gating of lower limb cortical somatosensory evoked potentials (SEPs)
      during passive and active foot movements.
AB  - We evaluated subcortical and cortical somatosensory evoked potentials (SEPs) in
      response to posterior tibial nerve stimulation in 4 experimental conditions of
      foot movement and compared them with the baseline condition of full relaxation.
      The experimental conditions were: (a) active flexion-extension of the stimulated
      foot; (b) active flexion-extension of the non-stimulated foot; (c) passive
      flexion-extension of the stimulated foot in complete relaxation; (d) tonic active
      flexion of the stimulated foot. We analyzed latencies and amplitudes of the
      subcortical P30 potential, of the contralateral pre-rolandic N37 and P50
      responses and of the P37, N50 and P60 potentials recorded over the vertex.
      Latencies did not vary in any of the paradigms. The amplitude of subcortical P30
      potential did not change during any of the paradigms. Among the cortical waves,
      P37, N50 and P60 amplitudes were significantly attenuated in all conditions
      except active movement of the non-stimulated foot (b). This attenuation was less
      during passive (c) than during active movements of the stimulated foot (a and d).
      The contralateral pre-rolandic waves N37 and P50 showed no significant decrease
      during any of the paradigms. These results suggest that gating occurs rostrally
      to the cervico-medullary junction, probably at cortical level. The different
      behavior of N37, P50 and P37, N50 cortical responses during movement of the
      stimulated foot provides evidence suggestive of a highly localized gating process
      occurring at cortical level. These potentials could reflect activation of
      separate, functionally distinct generators.

PMID- 9246069
TI  - Mapping of tibial nerve evoked magnetic fields over the lower spine.
AB  - Using a low-noise 49-channel dc-SQUID system spinal somatosensory evoked fields
      (SEF) were recorded which were generated by compound action currents evoked upon
      posterior tibial nerve stimulation. The SEF mapping showed the action current
      propagation along the sciatic nerve, lumbosacral plexus and cauda equina in
      parallel to simultaneously recorded electrical potentials (SEP). For a reliable
      intraindividual side-to-side comparison of spinal SEFs the right and left tibial
      nerves were stimulated in alternating order; this procedure minimizes artifactual
      inter-nerve SEF map differences due to eventual patient-to-sensor displacements
      which might occur in serial measurements. These large-area lumbar SEF mappings
      open up several clinical perspectives for magnetoneurography, in particular with
      respect to the 3D-localization of proximal conduction blocks.

PMID- 9246070
TI  - Somatosensory evoked potential monitoring in carotid surgery. II. Comparison
      between qualitative and quantitative scoring systems.
AB  - This paper compares the respective yields of our SEP scoring system
      ('qualitative' criteria), based on the subdivision of SEP abnormalities into
      mild, moderate, and severe abnormalities, and a quantitative one ('classical'
      criteria), based on a more than 1 ms CCT increase or 50% decrease of N20
      amplitude, for the detection of brain ischemia justifying shunt placement during
      carotid endarterectomy (CE). For that purpose, we examine the sensitivities of
      several neurophysiological parameters (the ipsilateral and contralateral CCT, the
      amplitudes of the ipsilateral and contralateral frontal and parietal SEPs) to
      carotid cross-clamping or to a drop of blood pressure. Our data first confirm
      that shunted patients developed a CCT increase and a decrease of N20 amplitude on
      the ipsilateral hemisphere. They further demonstrate that 50% of the patients who
      were immediately shunted on the basis of qualitative criteria would not have been
      shunted or would have been shunted with a longer delay on the basis of
      quantitative criteria. Simultaneously, the overall percentage of shunted patients
      was not significantly higher than in studies using the 'classical' criteria.
      Thus, it was hard to decide between the 'qualitative' and the 'classical'
      criteria on the basis of patient data. However, our 'qualitative' system appears
      advantageous in that it smooths out the influence of factors liable to interfere
      with the quantitative parameters.

PMID- 9246071
TI  - Somatosensory evoked potentials elicited by stimulation of lower-limb nerves in
      amyotrophic lateral sclerosis.
AB  - To determine lower limb somatosensory modifications in amyotrophic lateral
      sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) elicited by
      stimulation of tibial posterior nerves (TP), sural nerves (SN), saphenous
      internous nerves (SA), and medial plantar nerves (PL) of both limbs in 24 ALS
      patients, and compared the results with those from 17 normal subjects. Responses
      were recorded according to the international 10-20 system. Normal sensory
      conduction velocities of SN, SA and PL and H reflexes in soleus muscles were
      prerequisites for patient inclusion in this study. The results showed marked
      alterations in SEPs cortical components of all lower limb nerves, which could be
      related to abnormal sensory transmission (after spinal N22), or cortical
      abnormalities. We put forward the hypothesis of impairment of pyramidal control
      of the sensory system and Clark's column involvement to explain such anomalies.
      It was concluded that SEPs abnormalities in the lower limbs are a common feature
      in ALS.

PMID- 9246072
TI  - Non-painful and painful stimulation of human skin and muscle: analysis of
      cerebral evoked potentials.
AB  - The present study compared the cerebral processing of non-painful and painful
      cutaneous CO2 laser stimulation and intramuscular electrical stimulation in 11
      normal subjects. The overall wave form morphology of the long-latency evoked
      potentials (EPs) at the central vertex (Cz) was identical and surface topographic
      mappings of the 21-channel recordings showed similar distributions, suggesting
      involvement of common neural generators. However, the EPs caused by intramuscular
      stimulation differed from cutaneous stimulation in several distinct ways. First,
      the latency of the major positive and negative components were significantly
      shorter with intramuscular stimulation (N 128-145 ms; P 274-298 ms) compared to
      cutaneous stimulation (N 235-286 ms; P 371-383 ms) (P < 0.001). Second, the peak
      to-peak amplitude and root-mean-square values of intramuscular EPs recorded at Cz
      showed a ceiling effect in the painful range, whereas the laser EPs continued to
      increase in this range. Third, painful intramuscular, but not non-painful,
      stimulation caused a frontal activity which not was observed with cutaneous laser
      stimulation at any intensity. Conduction velocity measurements indicated
      activation of nociceptive A-delta afferents with cutaneous laser stimulation
      (10.2 +/- 0.2 m/s) and activation of a mixed nerve fiber population with
      intramuscular electrical stimulation (65.8 +/- 25.8 m/s). Differences between
      laser and intramuscular EPs may be due to different types and origins of
      activated afferent fibers. Laser EPs can be used specifically to assess cutaneous
      A-delta fiber function, whereas intramuscular EPs reflect the cerebral processing
      of a mixed afferent input from muscle tissue.

PMID- 9246073
TI  - Olfactory event-related potentials: older males demonstrate the greatest
      deficits.
AB  - Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz,
      Cz, and Pz electrode sites in 16 young adults (8M/8F) and 16 older adults (8M/8F)
      with inter-stimulus intervals (ISI) of 45, 60 and 90 s using amyl acetate as the
      odorant stimulus. N1, P2, and N2 peak amplitudes and latencies were measured.
      Young participants demonstrated significantly shorter peak latencies than older
      participants. Older males demonstrated significantly smaller peak amplitudes than
      the other participant groups. Peak amplitudes also increased with longer ISIs for
      older males. The OERP is compared to traditional olfactory psychophysical
      testing.

PMID- 9246074
TI  - Is it really a mismatch negativity? An assessment of methods for determining
      response validity in individual subjects.
AB  - Mismatch negativity (MMN) responses were collected from 86 normal school-age
      children in response to synthesized speech syllables, /wa/and two variants of
      /ba/. Waveform characteristics and statistical properties of the responses were
      analyzed across stimulus conditions in order to assess methods for determining
      response validity in individuals. Methods were compared using signal detection
      theory techniques. Criteria based on measurements of response area, onset
      latency, and duration were the best indicators of response validity. Also a
      promising indicator of validity was the interval of significance based on Z
      transformations determined by considering the variance of the underlying noise
      distribution. Correlations of individual responses with the grand average and
      integral calculations of the response negativity showed somewhat lower d' values.
      Statistical methods which utilized response subaverages were the poorest
      indicators of response validity. Likely the methods are limited primarily by the
      signal to noise ratio of the MMN compared to the underlying physiologic noise.
      Improvement of the signal to noise ratio remains a significant factor in the
      interpretation of MMN for individual subjects.

PMID- 9246075
TI  - Relative value of the inion and mid-parietal locations as additional recording
      sites in pattern reversal visual evoked potentials.
AB  - Although the P100 response of pattern reversal visual evoked potentials (PRVEPs)
      is most commonly recorded from the midline occipital site (MO), the response at
      this location can occasionally be absent or poorly defined due to anatomical
      variability of the visual cortex. In these cases, the American
      Electroencephalographic Society Evoked Potential Guidelines recommends recording
      from the mid-parietal (MP) and Inion electrode sites. In this study, we compared
      the amplitude of the P100 component recorded simultaneously from MO, MP and the
      Inion. PRVEPs obtained following stimulation with 30' check sizes from 155
      consecutive patients (310 eyes) over a 2 year period were analyzed. At each of
      the 3 recording sites, the peak amplitude of P100 was calculated as N75-P100,
      P100-N145, and the sum of N75-P100 and P100-N145. There was a statistically
      significant difference between the electrode sites for all 3 methods of amplitude
      measurement (one-way ANOVA; P < 0.0001). For each method of measurement, there
      was no significant difference between P100 amplitude at MO or the Inon, but a
      significantly reduced amplitude at MP compared to both the MO and Inion electrode
      sites (post hoc Scheffe, P < 0.05). The P100 amplitude was highest at the Inion
      in 18% of responses, including cases where the amplitude at that site was at
      least twice that at MO. In no case was the amplitude highest at MP. Our results
      indicate that the Inion is a better recording site compared to MP when acquiring
      PRVEPs, is often complementary to MO, and should be the first additional site to
      be used when extra channels are available.

PMID- 9246076
TI  - Different effects of cholinergic agents on responses recorded from the cat visual
      cortex and lateral geniculate nucleus dorsalis.
AB  - We investigated the effect of cholinergic agents on the cat visual evoked
      potentials (VEPs) recorded from the primary visual cortex (V1) and lateral
      geniculate nucleus dorsalis (LGNd) to determine on which level of the visual
      pathway the cholinergic system acts. VEPs to the alternation of 0.1 cycles per
      degree sinusoidal gratings at 1 and 4 Hz were recorded from N2O-anesthetized cats
      directly from the surface of V1 and LGNd. The depth of recording in LGNd was
      determined by the site where the maximal response was obtained by 1 Hz
      stimulation. VEPs to 4 Hz stimulation, which showed sinusoidal waveforms and were
      analyzed by fast Fourier transforms, were used as indicators for modulation by
      cholinergic agents. Physostigmine, an acetylcholinesterase inhibitor, 0.7 mg/kg
      i.v., suppressed the amplitude of the responses more at V1 (suppression ratio:
      mean +/- SD, 85.4 +/- 9.3%) than at LGNd (32.4 +/- 30.7%) (P < 0.05). Conversely,
      scopolamine, a muscarinic receptor blocker, 0.7 mg/kg i.v., increased the
      amplitude of the responses more at V1 (enhancement ratio: mean +/- SD, 60.3 +/-
      22.3%) than at LGNd (-22.2 +/- 22.5%) (P < 0.05). These results indicate that the
      V1 changes reflect a direct cortical cholinergic effect, probably by modulating
      the cholinergic projection from the nucleus basalis of Meynert to V1.

PMID- 9246077
TI  - Effect of radial shortening on muscle length and moment arms of the wrist flexors
      and extensors.
AB  - The purpose of this study was to determine the effect of distal radial shortening
      on muscle length and moment arm of the wrist flexors and extensors. In eight
      cadaveric upper extremities, distal radius fractures were simulated by an
      ostectomy. The distal radius was progressively shortened by 2.5, 5.0, 7.5, and 10
      mm. Changes in the resting length of the flexor carpi radialis and ulnaris,
      extensor carpi radialis longus and brevis, and extensor carpi ulnaris muscles
      were measured with rotary potentiometers at neutral position, flexion, extension,
      and radial and ulnar deviation of the wrists. The wrists were passively moved
      through flexion-extension and radioulnar deviation, and tendon excursions and
      wrist joint angulation were recorded simultaneously. Tendon moment arms were
      derived from tendon excursions and joint motion. The results showed that either
      muscle length or moment arm of the principal wrist flexors and extensors was
      significantly affected by the radial shortening. Muscle length decreased
      significantly after radial shortening in all the wrist flexors and extensors
      except for the extensor carpi ulnaris. The moment arm of the extensor carpi
      ulnaris tendon decreased significantly during either wrist flexion-extension or
      radioulnar deviation. The extensor carpi radialis brevis and flexor carpi ulnaris
      tendons also showed a significant decrease in their moment arms during radioulnar
      deviation of the wrist. Radial shortening of only 2.5 mm caused statistically
      significant changes in muscle length and moment arm of the wrist flexors and
      extensors. Increasing the extent of radial shortening exaggerated the
      biomechanical changes in the wrist motors. These results validate the importance
      of normal radial length for wrist kinetics and, from a biomechanical perspective,
      support complete correction of radial shortening after distal radius fractures.

PMID- 9246078
TI  - Changes in the flexibility characteristics of the ankle complex due to damage to
      the lateral collateral ligaments: an in vitro and in vivo study.
AB  - This study was part of a long-term effort to develop a reliable diagnostic
      procedure for ankle ligament injuries. Earlier efforts led to the development and
      validation of a six-degrees-of-freedom instrumented linkage capable of measuring
      the flexibility characteristics of the ankle complex in vitro and in vivo. The
      major goal of the present study was to determine if these flexibility
      measurements are sufficiently sensitive to detect the presence of damage to the
      lateral collateral ligaments of the ankle joint both in vitro and in vivo. The in
      vitro testing was conducted on the legs from six fresh cadavers before and after
      serial sectioning of the anterior talofibular ligament and the calcaneofibular
      ligament. The flexibility in inversion-eversion, anterior drawer, and internal
      external rotation was measured before and after resection of the ligaments. The
      in vivo testing was conducted on five patients with unilateral injuries to the
      ankle ligament. The flexibility evaluation used for in vitro specimens was also
      performed on both the injured and the intact ankles. For the in vitro testing,
      the data analysis was based on comparison of flexibility values before and after
      resection of the ligaments, whereas the data analysis for the in vivo testing was
      based on comparison of the flexibility of the injured joint with that of the
      intact contralateral joint. The results of the in vitro study indicated that both
      an isolated rupture of the anterior talofibular ligament and combined damage of
      the anterior talofibular and calcaneofibular ligaments produce statistically
      significant changes in flexibility. Furthermore, the most sensitive parameters to
      the presence of ligament injuries were found to be early flexibility in anterior
      drawer, early flexibility in inversion, and the amount of coupling between
      internal rotation and inversion. These parameters provided a basis for
      differentiating between an isolated injury to the anterior talofibular ligament
      and a combined anterior talofibular and calcaneofibular ligament injury. For an
      isolated anterior talofibular ligament injury, a significant increase in
      flexibility in anterior drawer was present, whereas the increase in inversion
      flexibility or in the amount of coupling was insignificant. However, the
      increases in inversion flexibility and the amount of coupling became significant
      when both ligaments were involved. The results of the in vivo study indicated
      that significant changes in flexibility can be detected in patients with lateral
      ankle injuries. Finally, both the in vitro and in vivo results suggest that
      development of a reliable diagnostic test for ankle ligament injury based on
      changes in passive flexibility may be possible.

PMID- 9246079
TI  - Uncinate processes and Luschka joints influence the biomechanics of the cervical
      spine: quantification using a finite element model of the C5-C6 segment.
AB  - A fully three-dimensional finite element model of a C5-C6 motion segment of the
      human spine was developed and validated for the purpose of investigating the
      biomechanical significance of uncinate processes and Luschka joints. The original
      intact cervical model was modified to create two additional models. The first
      simulated the absence of Luschka joints by replacing the fissures with continuous
      annulus fibrosus and leaving the uncinate processes intact. The second model
      simulated a surgical resection of the uncinate processes, while leaving the
      Luschka joints intact. The results of these two models were compared with the
      intact model, which served as a baseline; thus, the relative contributions of
      these two structures to cervical motion were established. With use of our model,
      it was possible, for the first time, to provide quantitative data concerning the
      source of coupled motions in the lower cervical spine. In principle, the results
      from this model support the hypothesis of Penning and Wilmink. Our results
      indicate that the facet joints and Luschka joints are the major contributors to
      coupled motion in the lower cervical spine and that the uncinate processes
      effectively reduce motion coupling and primary cervical motion (motion in the
      same direction as load application), especially in response to axial rotation and
      lateral bending loads. Luschka joints appear to increase primary cervical motion,
      showing an effect on cervical motion opposite to that of the uncinate processes.
      Surgeons should be aware of the increase in motion accompanied by resection of
      the uncinate processes.

PMID- 9246080
TI  - Reproducibility of the kinematics and kinetics of the lower extremity during
      normal stair-climbing.
AB  - The purpose of this study was to examine the intrasubject reproducibility of the
      kinematic and kinetic measures of the lower extremity during normal stair
      climbing. Three-dimensional video and force-plate data were collected for three
      trials per subject during each of three conditions: ascending, descending, and
      level walking. Three-dimensional angles and moments of the ankle, knee, and hip
      joints were calculated. The coefficient of multiple correlation was used to
      determine the intrasubject reproducibility of joint angles and resultant moments.
      Analysis of variance with repeated measures was conducted to compare the
      magnitudes of the coefficients between different steps, different joints, and
      different joint functions. The results showed that (a) generally, the kinematic
      and kinetic measures of normal subjects climbing stairs were reproducible; (b)
      the kinetic measures during the transition steps from level walking to ascending
      and from descending to level walking were significantly less reproducible than
      those during the other steps; (c) the data from the sagittal plane were more
      reproducible than those from the other two planes; and (d) the kinetic measures
      were more reproducible than the kinematic measures, especially for abduction
      adduction and internal-external rotation.

PMID- 9246081
TI  - Characterization of regional and age-related variations in the growth of the
      rabbit distal femur.
AB  - Fluorochrome labeling and microcomputed tomography were used to completely
      characterize the regional and age-related variations in bone growth in the distal
      femur of the young rabbit. Use of the microcomputed tomography system, in
      conjunction with the more routine fluorochrome labeling, allows the investigation
      of changes in shape that occur during development. The growth plate in the distal
      femur studied here is remarkable for several reasons. First, growth rates of as
      much as 700 microns/day were measured, a much higher rate than those typically
      measured in other species or in more mature animals. In addition, regional
      variations in bone growth rates of as much as 300 microns/day were identified in
      the 6-week-old rabbit. These variations resulted in the formation of a complex
      curvature in the growth plate, including four mammillary processes. Identifying
      the factors that regulate this type of regional variation may be especially
      useful in understanding the causes for angular deformities such as tibia vara or
      developmental dysplasias.

PMID- 9246082
TI  - Structure and function of embryonic growth plate in the absence of functioning
      skeletal muscle.
AB  - Normal growth and development of the skeleton require the presence of viable,
      actively contracting skeletal muscle throughout the fetal period. A chick embryo
      model of midgestation chemical paralysis and secondary muscle atrophy was used to
      test the hypothesis that functioning muscle stimulates the growth of long bones
      by influencing the proliferation, differentiation, and hypertrophy of
      chondrocytes in cartilage of the epiphysis and growth plate. Paralysis did not
      alter the overall developmental stage of the long bone or the organization of the
      growth plate. Compared with controls, however, uptake of bromodeoxyuridine in the
      paralyzed chick was reduced by 27-55% in the chondroepiphysis and uppermost zone
      of the tibial growth plate, indicating reduced proliferation of chondrocytes. A
      specific reduction in the size of the proliferative zone and a reduced number of
      proliferating cells were also observed. By contrast, in the second, post
      proliferative zone of the growth plate, the height of the zone was unchanged and
      its area was only slightly reduced compared with controls. Finally, median
      hypertrophic cell profile area, a measure of cell size, was not significantly
      affected by paralysis, although frequency analysis revealed modest numerical
      reductions in the population of the largest hypertrophic chondrocytes in the
      paralyzed group. These data suggest that the role of functioning fetal muscle in
      maintaining proper skeletal growth may be mediated primarily through specific
      stimulation of the recruitment or proliferation of immature chondrocytes, or of
      both.

PMID- 9246083
TI  - Recombinant bone morphogenetic protein (BMP)-2 regulates costochondral growth
      plate chondrocytes and induces expression of BMP-2 and BMP-4 in a cell maturation
      dependent manner.
AB  - This study examined the effect of recombinant human bone morphogenetic protein-2
      on several parameters of growth, differentiation, and matrix synthesis and on the
      endogenous production of mRNA of bone morphogenetic proteins 2 and 4 by growth
      plate chondrocytes in culture. Chondrocytes from resting and growth zones were
      obtained from rat costochondral cartilage and cultured for 24 or 48 hours in
      medium containing 0.05-100 ng/ml recombinant human bone morphogenetic protein-2
      and 10% fetal bovine serum. Incorporation of [3H]thymidine, cell number, alkaline
      phosphatase specific activity, incorporation of [3H]proline into collagenase
      digestible protein and noncollagenase-digestible protein, and incorporation of
      [35S]sulfate were assayed as indicators of cell proliferation, differentiation,
      and extracellular matrix synthesis. mRNA levels for bone morphogenetic proteins 2
      and 4 were determined by Northern blot analysis. Recombinant human bone
      morphogenetic protein-2 increased the incorporation of [3H]thymidine by quiescent
      resting-zone and growth-zone cells in a similar manner, whereas it had a
      differential effect on nonquiescent cultures. At 24 and 48 hours, 12.5-100 ng/ml
      recombinant human bone morphogenetic protein-2 caused a dose-dependent increase
      in cell number and DNA synthesis in resting-zone chondrocytes. No effect was seen
      in growth-zone cells. Recombinant human bone morphogenetic protein-2 stimulated
      alkaline phosphatase specific activity in resting-zone chondrocytes in a bimodal
      manner, causing significant increases between 0.2 and 0.8 ng/ml and again between
      25 and 100 ng/ml. In contrast, alkaline phosphatase specific activity in growth
      zone chondrocytes was significantly increased only between 12.5 and 100 ng/ml.
      Recombinant human bone morphogenetic protein-2 increased the production of both
      collagenase-digestible protein and noncollagenase-digestible protein by resting
      zone and growth-zone cells, but incorporation of [35S]sulfate was unaffected.
      Administration of recombinant human bone morphogenetic protein-2 also increased
      incorporation of [3H]uridine in both resting-zone and growth-zone chondrocytes;
      these cells produced mRNA for bone morphogenetic proteins 2 and 4. Bone
      morphogenetic protein-2 mRNA levels in both resting-zone and growth-zone
      chondrocytes increased in the presence of recombinant human bone morphogenetic
      protein-2; however, bone morphogenetic protein-4 mRNA levels in growth-zone cells
      decreased under its influence, and those in resting-zone cells were upregulated
      only with a dose of 10 ng/ml. This indicates that recombinant human bone
      morphogenetic protein-2 regulates chondrocyte proliferation, differentiation, and
      matrix production, and the effects are dependent on the stage of cell maturation.
      Resting-zone chondrocytes were more sensitive, suggesting that they are targeted
      by bone morphogenetic protein-2 and that this growth factor may have autocrine
      effects on these cells.

PMID- 9246084
TI  - Effects of continuous distraction on cartilage in a moving joint: an
      investigation on adult rabbits.
AB  - An animal model, using distraction force on adult rabbits, was developed to study
      the effects of nonweight-bearing on articular cartilage in a moving joint.
      Histologic evaluation was used to compare the morphology of chondrocytes,
      safranin O intensity, cartilage thickness, and structural changes between the
      test and contralateral joints. At 3 and 6 weeks, the chondrocytes in superficial
      and intermediate zones were round, with an increase in cellular volume density
      and mean cell volume and with less metachromasia; the safranin O intensity and
      cartilage thickness were the same as in the controls. In cartilage of the 9-week
      group, mean cell volume decreased with cell cloning in the superficial zone,
      while numerical density increased and mean matrix volume per cell decreased in
      the superficial and intermediate zones. The cartilage, with a 34% reduction in
      thickness and a 53-72% decrease in safranin O intensity from the superficial to
      the deep zone, had superficial fibrotic proliferation, surface erosion or
      depression, and tidemark irregularity. Continuous distraction in a moving joint
      caused morphological changes in chondrocytes prior to degeneration of cartilage.
      These results support the hypothesis that the forces perceived by cells may
      dictate their shape and then stimulate alterations in cellular biochemistry and
      matrix metabolism.

PMID- 9246085
TI  - Biochemical and density assessment of the new bone in late remodeling after
      callus distraction.
AB  - Biochemical changes in a canine bone-lengthening model were characterized 5
      months after surgery. The mineral content and the total amount of EDTA
      extractable noncollagenous proteins, insulin-like growth factor-I, and
      osteocalcin were determined for the lengthened callus, and a gradient density
      fractionation analysis of bone powder particles was performed. The results were
      compared with two other areas of the lengthened tibia and one region of the
      contralateral tibia. The mineral and osteocalcin contents showed significant
      decreases, whereas the hydroxyproline concentration was significantly increased.
      Neither the insulin-like growth factor-I content nor the concentration of EDTA
      extractable proteins was significantly different in any of the examined regions.

PMID- 9246086
TI  - Comparison of the tissue response to absorbable self-reinforced polylactide
      screws and metallic screws in the fixation of cancellous bone osteotomies: an
      experimental study on the rabbit distal femur.
AB  - The availability of absorbable fracture-fixation devices for clinical use calls
      for better knowledge of the reaction of bone tissue to absorbable polyester
      implants as compared with similar metallic devices. To examine and compare the
      tissue response to biodegradable and metallic screws within cancellous bone, a
      transverse transcondylar osteotomy of the distal femur was fixed with absorbable
      self-reinforced polylevolactide screws in 35 rabbits and with stainless-steel
      screws in 35 rabbits. New bone formation and consolidation of the osteotomy were
      examined histologically, histomorphometrically, and microradiographically within
      standardized sample fields 1, 3, 6, 12, 24, 36, and 48 weeks postoperatively. The
      intact contralateral femur served as the control. A vigorous osteoconductive
      response to the polylevolactide screws was observed at 3 weeks postoperatively,
      and the osteoid surface fraction was significantly higher in all follow-ups than
      in the contralateral femora. In the femora with metallic screws, new bone
      formation was seen 3, 6, and 12 weeks postoperatively, but at 24, 36, and 48
      weeks the osteoid surface fraction did not differ significantly from that of the
      intact control femora. The total bone area was significantly larger in the femora
      with self-reinforced polylevolactide screws than in the control bone 6-48 weeks
      postoperatively; in the femora with metallic screws, this was found only at 6 and
      12 weeks. After 48 weeks, the femora fixed with metallic screws had statistically
      smaller total bone area than the intact control femora. Solid bone union was seen
      in 84% of the osteotomies in the self-reinforced polylevolactide group and in 76%
      of those in the metallic group after 3 weeks or more. No signs of degradation of
      the self-reinforced polyleuolactide implant and only a mild foreign-body reaction
      with no accumulations of inflammatory cells to either self-reinforced
      polylevolactide or metallic screws were observed during the follow-up period.
      Both types of screws seemed to induce an osteostimulatory response around their
      threads. This phenomenon was transient for metallic screws but lasted for at
      least 48 weeks for self-reinforced polylevolactide screws. The polylevolactide
      screw does not seem to cause osteopenia at the implantation site. The fixation
      properties of both self-reinforced polylevolactide screws and metallic screws
      appear to be sufficient for the fixation of small fragments of cancellous bone.

PMID- 9246087
TI  - Acute effects of periarterial sympathectomy on the cutaneous microcirculation.
AB  - The clinical effects of peripheral sympathectomy on patients with vaso-occlusive
      disease are often dramatic and include relief of pain, improved quality of life,
      and healing of ulcers. Peripheral periarterial sympathectomy is known to increase
      skin temperature and to maximize the nutritional component of peripheral blood
      flow, but the pathophysiology of vaso-occlusive disease and the physiologic
      mechanisms of this treatment are unknown. In this study, the acute effects of
      periarterial sympathectomy were directly observed in a rabbit ear model of
      digital microcirculation (arterioles, arteriovenous anastomoses, and venules).
      The effects of periarterial sympathectomy on cutaneous perfusion and total flow
      were also examined using laser Doppler perfusion imaging and digital temperature
      measurements. The central auricular artery became dilated (50-100%) immediately
      after sympathectomy; the arterioles, arteriovenous anastomoses, and venules
      dilated to 165, 156, and 223%, respectively, at 30 minutes and to 187, 174, and
      204%, respectively, at 60 minutes, relative to their baseline diameters prior to
      sympathectomy. Laser Doppler perfusion imaging values and ear temperatures were
      noted to increase after sympathectomy (8.9%, 3 degrees C), although the core
      temperature of the rabbit did not change. Thus, acute periarterial sympathectomy
      can (a) effectively reduce the vascular tone of the distal microvasculature and
      (b) increase total microcirculatory perfusion-cutaneous and thermoregulatory-by
      both venular and arteriolar dilation. Periarterial sympathectomy has the clinical
      potential to increase nutritional blood flow, thereby ameliorating the signs and
      symptoms of ischemia associated with thermoregulatory abnormalities. Dilation of
      the arteriovenous anastomoses, with a subsequent reduction in vascular
      resistance, may contribute to the increased cutaneous temperature noted after
      sympathectomy.

PMID- 9246088
TI  - Characterization of a rabbit model of staphylococcal osteomyelitis.
AB  - We previously described a rabbit osteomyelitis model that involved the direct
      introduction of Staphylococcus aureus into devascularized bone. To further
      evaluate the model, we performed experiments aimed at correlating the
      microbiological, radiographic, and histologic parameters involved in the
      development of experimental osteomyelitis. Using the strain UAMS-1, we achieved
      an infection rate of 75% with an inoculum as small as 2 x 10(3) colony-forming
      units. However, development of significant radiographic and histologic signs of
      disease required an inoculum of at least 2 x 10(4) colony-forming units.
      Radiographic signs were minimal 1 week after infection and progressed steadily to
      a maximum 3 weeks after infection. In contrast, histologic signs of disease were
      observed within 1 week and remained essentially unchanged throughout the 4-week
      evaluation period. Unlike the results obtained with UAMS-1, rabbits infected with
      the heavily encapsulated Staphylococcus aureus strain Smith diffuse exhibited
      little evidence of disease even when infected with 2 x 10(6) colony-forming
      units. The reduced virulence of strain Smith diffuse was surprising given its
      greatly enhanced virulence (relative to UAMS-1) in a murine peritonitis model of
      staphylococcal disease. These results suggest that UAMS-1 expresses virulence
      factors that are important in the pathogenesis of osteomyelitis and that some or
      all of these virulence factors are either absent or are not expressed in strain
      Smith diffuse. Most importantly, the results suggest that our model may be
      appropriate for the identification and characterization of these virulence
      factors.

PMID- 9246089
TI  - Effects of static fingertip loading on carpal tunnel pressure.
AB  - The purpose of this study was to explore the relationship between carpal tunnel
      pressure and fingertip force during a simple pressing task. Carpal tunnel
      pressure was measured in 15 healthy volunteers by means of a saline-filled
      catheter inserted percutaneously into the carpal tunnel of the nondominant hand.
      The subjects pressed on a load cell with the tip of the index finger and with 0,
      6, 9, and 12 N of force. The task was repeated in 10 wrist postures: neutral; 10
      and 20 degrees of ulnar deviation; 10 degrees of radial deviation; and 15, 30,
      and 45 degrees of both flexion and extension. Fingertip loading significantly
      increased carpal tunnel pressure for all wrist angles (p = 0.0001). Post hoc
      analyses identified significant increase (p < 0.05) in carpal tunnel pressure
      between unloaded (0 N) and all loaded conditions, as well as between the 6 and 12
      N load conditions. This study demonstrates that the process whereby fingertip
      loading elevates carpal tunnel pressure is independent of wrist posture and that
      relatively small fingertip loads have a large effect on carpal tunnel pressure.
      It also reveals the response characteristics of carpal tunnel pressure to
      fingertip loading, which is one step in understanding the relationship between
      sustained grip and pinch activities and the aggravation or development of median
      neuropathy at the wrist.

PMID- 9246090
TI  - Immunolocalization of cytokines and their receptors in adhesive capsulitis of the
      shoulder.
AB  - The purpose of this study was to test the hypothesis that specific cytokines are
      involved in the initiation and evolution of the fibrotic process in adhesive
      capsulitis of the shoulder. After approval from the Institutional Review Board,
      biopsies of shoulder capsule and synovium were collected during shoulder
      arthroscopy from 19 patients with adhesive capsulitis, 14 patients with
      nonspecific synovitis and no fibrosis or clinical evidence of adhesive
      capsulitis, and seven patients undergoing surgery for another pathology who had a
      normal capsule and synovium. Immunohistochemical localization with monoclonal
      antibodies to transforming growth factor-beta and its receptor, platelet-derived
      growth factor and its receptor, basic fibroblast growth factor, interleukin-1
      beta, tumor necrosis factor-alpha, and hepatocyte growth factor was performed
      using standard immunoperoxidase techniques. The frequency of cytokine staining
      was correlated with the clinical diagnosis. Synovial cells, fibroblasts, T-cells,
      and B-cells were identified with specific antibodies, and newly synthesized
      matrix was examined for type-I and type-III collagen by immunohistochemical
      staining. The predominant cell types present were synovial cells and fibroblasts.
      Staining for type-III collagen in adhesive capsulitis tissues indicated new
      deposition of collagen in the capsule. There was staining for transforming growth
      factor-beta and its receptor, platelet-derived growth factor and its receptor,
      interleukin-1 beta, and tumor necrosis factor-alpha in adhesive capsulitis and
      nonspecific synovitis tissues, compared with minimal staining in normal capsule.
      Staining was more frequent in synovial cells than in capsular cells. The
      frequency of cell and matrix staining for transforming growth factor-beta,
      platelet-derived growth factor, and hepatocyte growth factor was greater in
      adhesive capsulitis tissues than in those from patients with nonspecific
      synovitis. No difference in the frequency of staining between primary
      (idiopathic) and secondary adhesive capsulitis was found. The results of this
      study indicate that adhesive capsulitis involves both synovial hyperplasia and
      capsular fibrosis. Cytokines such as transforming growth factor-beta and platelet
      derived growth factor may be involved in the inflammatory and fibrotic processes
      in adhesive capsulitis. Matrix-bound transforming growth factor-beta may act as a
      persistent stimulus, resulting in capsular fibrosis. Understanding the basic
      pathophysiology of adhesive capsulitis is an important step in the development of
      clinically useful antifibrotic agents that may serve as novel treatments for
      patients with this conditions.

PMID- 9246091
TI  - Small-angle HeNe laser light scatter and the compressive modulus of articular
      cartilage.
AB  - Light scattering is a widely used technique for probing the microarchitecture and
      interactions of biological materials and solutions. In this paper, we describe
      the use of this method in the study of articular cartilage. The experiments
      presented utilize small-angle static scattering of HeNe laser light (632.8 nm)
      from 40 microns thick samples of cartilage taken from the superficial zone of
      baboon femoral condyle. The specimens were taken from a total of 26 sites in
      eight animals of various ages. In addition to measuring the dependence of the
      intensity of scattered light on scatter angle, we performed mechanical testing at
      the test sites using creep-indentation techniques. The results from the optical
      and mechanical experiments were compared, and a significant correlation was noted
      between the average scatter angle and the compressive aggregate modulus. In
      addition, it was noted that the cartilage of skeletally immature animals had a
      smaller aggregate modulus and scattered to a higher average angle than the
      cartilage of skeletally mature animals. A quantitative theory was developed to
      explain the relation, between mechanical and optical properties in terms of the
      degree of order in the spatial arrangement of the collagen fibers in cartilage.

PMID- 9246092
TI  - Nitric oxide and proteoglycan turnover in rabbit articular cartilage.
AB  - Articular chondrocytes are known to synthesize large amounts of nitric oxide in
      response to exposure to interleukin-1, but the role of this radical in
      proteoglycan turnover remains controversial. In this study, we used two different
      inhibitors of nitric oxide synthase, NG-methyl-L-arginine and thiocitrulline, to
      study the effects of nitric oxide on the synthesis and breakdown of proteoglycan
      in rabbit articular cartilage. Synthesis of nitric oxide by cartilage slices in
      response to treatment with interleukin-1 and a partially purified mixture of
      synovial cytokines known as chondrocyte-activating factors peaked during the
      first 2 days of culture and then fell to low levels, despite daily replenishment
      with fresh medium and cytokines to the cultures. The production of nitric oxide
      was completely inhibited by NG-methyl-L-arginine and thiocitrulline. Interleukin
      1 and the chondrocyte-activating factors inhibited proteoglycan synthesis and
      accelerated proteoglycan breakdown in the slices of cartilage. Both nitric oxide
      synthase inhibitors substantially counteracted the suppression of proteoglycan
      synthesis but exacerbated proteoglycan catabolism occurring in response to
      interleukin-1 and the chondrocyte-activating factors. The accelerated catabolism
      was associated with increased levels of matrix metalloproteinases in the
      conditioned medium. This dual effect of nitric oxide complicates decision making
      with regard to the possible clinical applications of nitric oxide agonists or
      antagonists in diseases of cartilage.

PMID- 9246093
TI  - Subfracture insult to a knee joint causes alterations in the bone and in the
      functional stiffness of overlying cartilage.
AB  - The current criteria used by the automotive industry for predicting joint injury
      are based on fracture of bone, but clinical studies suggest that chronic diseases
      such as osteoarthrosis can occur from a single blunt insult without bone
      fracture. In the current study, blunt insults were delivered to the
      patellofemoral joints of rabbits without producing bone fractures. Biomechanical
      and histological studies were performed on joint tissues at various times after
      insult. The functional integrity of the retropatellar cartilage on the lateral
      facet was measured with mechanical indentation experiments, and the thickness of
      the subchondral bone was measured from histological sections. Impacts produced
      surface lesions on the retropatellar cartilage. The thickness of the subchondral
      bone in representative animals tended to increase with time after insult, and the
      bone exhibited significant thickening at 12 months. The overlying cartilage
      showed signs of degeneration. However, the mechanical stiffness of the cartilage
      did not change until 12 months after the insult.

PMID- 9246094
TI  - Treatment with recombinant human macrophage colony-stimulating factor resorbs
      blood clot and restores osteoclastogenesis in heterotopic bone induced by
      partially purified native bone morphogenetic protein in osteopetrotic (op/op)
      mice.
AB  - Native bone morphogenetic protein and associated noncollagenous proteins induced
      the formation of heterotopic bone in the hindquarter muscles of osteopetrotic
      (op/op) mice and those of their phenotypically normal littermates (+/?). In op/op
      mice, the heterotopic bone consisted of a disorganized, densely packed mixture of
      irregular calcified cartilage, osteoid, chondro-osteoid, and fibrous tissue.
      Injections of recombinant human macrophage colony-stimulating factor initiated
      bone resorption that began in the peripheral vascularized regions of the
      metaphyses and continued in central areas of uncalficified avascular chondro
      osteoid. On vascularized surfaces, osteoclasts were stained with tartrate
      resistant acid phosphatase. In op/op mice treated with macrophage colony
      stimulating factor, the osteoclasts were small, with only two or three nuclei,
      and they did not exhibit tartrate-resistant acid phosphatase staining. In
      untreated op/op mice, surgical blood clots persisted in the heterotopic sites as
      late as 3 weeks after the operation, whereas in treated op/op mice, the blood
      clots were absorbed almost as rapidly as in normal mice. Histologically,
      recombinant human macrophage colony-stimulating factor restored normal macrophage
      functions: absorption and organization of blood clot, osteoclastogenesis,
      synthesis of tartrate-resistant acid phosphatase, bone remodeling, islands of
      myelopoiesis, and construction of an ossicle complete with a cortex and a medulla
      filled with functioning hematopoietic bone marrow.

PMID- 9246095
TI  - Regulation of the expression of the type-II collagen gene in periosteum-derived
      cells by three members of the transforming growth factor-beta superfamily.
AB  - Although transforming growth factors-beta and bone morphogenetic proteins are
      both capable of inducing bone formation in vivo, the target cells of their
      osteoinductive actions may be different. To evaluate periosteal cells as
      potential targets of the actions of transforming growth factor-beta and bone
      morphogenetic protein, we investigated the ability of three members of the
      transforming growth factor-beta superfamily to modulate expression of the gene
      encoding the alpha 1(II) chain of type-II collagen in periosteum-derived cells in
      vitro. The results demonstrate that transforming growth factor-beta mRNA is
      expressed by periosteum-derived cells and that exogenous transforming growth
      factor-beta 1 acts to upregulate expression of the gene encoding collagen alpha
      1(II). This effect was observed as early as 12 hours after administration of
      transforming growth factor-beta 1 but was not observed in response to bone
      morphogenetic proteins 3 or 4. No synergy was demonstrated between transforming
      growth factor-beta 1 and bone morphogenetic protein-3 in the ability to
      upregulate expression of the collagen alpha 1(II) gene. These results support the
      hypothesis that committed periosteal mesenchymal cells are cellular targets of
      the action of transforming growth factor-beta.

PMID- 9246096
TI  - Correspondence between theoretical models and dual energy x-ray absorptiometry
      measurements of femoral cross-sectional growth during adolescence.
AB  - We have developed an analytical model of long bone cross-sectional ontogeny in
      which appositional growth of the diaphysis is primarily driven by mechanical
      stimuli associated with increasing body mass during growth and development. In
      this study, our goal was to compare theoretical predictions of femoral diaphyseal
      structure from this model with measurements of femoral bone mineral and geometry
      by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral
      geometry and structure were made previously in 101 Caucasian adolescents and
      young adults 9-26 years of age. The data on measured bone mineral content and
      calculated section modulus were compared with the results of our analytical model
      of cross-sectional development of the human femur over the same age range. Both
      bone mineral content and section modulus showed good correspondence with
      experimental measurements when the relationships with age and body mass were
      examined. Strong linear relationships were evident for both parameters when
      examined as a function of body mass.

PMID- 9246097
TI  - Anatomy of the human patellofemoral joint articular cartilage: surface curvature
      analysis.
AB  - Articular cartilage surfaces of 49 human patellae and 24 distal femora were
      characterized by identifying distinctive features with surface curvature
      analysis. Paired specimens from the same donor generally exhibited natural
      symmetry, so only results from nonpaired specimens were considered (39 patellae
      and 19 femora). In 23 of 39 patellae, proximal median and lateral transverse
      ridges extended to form an oblique ridge resembling a skewed lambda (lambda).
      Most of the unpaired patellae (37 of 39) exhibited only a single lateral
      transverse ridge, and most (32 of 39) had an odd facet. All but one patella
      exhibited a concave depression in the lateral and medial facets and a sellar area
      in the proximal region. All distal femoral surfaces exhibited a sellar trochlea.
      The concavity of the trochlea was greatest in the posterior aspect, near the
      intercondylar notch.

PMID- 9246098
TI  - Robertsonian translocations in Paget's disease of bone.
AB  - The karyotypes of 14 patients with Paget's disease of bone were studied. The
      patients were recruited from our bone metabolism clinic where they received
      specific therapy for their skeletal disease. Eight of the 14 patients had
      chromosomal translocations localized to the D and G groups. None of the patients
      were related to one another, nor had any had the same lifelong environment. Thus,
      57% of a sample of active patients with Paget's disease had Robertsonian
      translocations. By comparison, an age and sex-matched group of eight controls and
      13 patients with osteoporosis who had been treated with bisphosphonates
      demonstrated no Robertsonian translocations. The prevalence of Robertsonian
      translocations in 14,000 newborns was reported to be 0.1%. These data suggest
      that a factor from the environment introduced during the lifetime of the patient
      could be present and could, in addition to genetic factors, affect gene
      replication during the development of Paget's disease.

PMID- 9246099
TI  - [Mitral surgery: prognostic and survival factors. Value of the French score].
AB  - OBJECTIVES: Conservative mitral surgery is the preferred treatment for mitral
      regurgitation whatever the etiology. Morbidity and mortality figures, both during
      hospitalization and after long-term follow-up, are better than for mitral valve
      replacement. This difference could result from a selection bias or express a
      specific effect of conservative mitral surgery on survival. In addition, concerns
      about cost-containment justify rigorous analysis of treatment quality. The
      "French" score can be used for preoperative assessment of individual and
      population operative risk and for inter-institution comparisons. Its value for
      assessing overall survival is unknown. METHODS: Using the French score, we
      compared the clinical features and laboratory data in 100 patients who underwent
      conservative mitral valve surgery and in 35 patients who had valve replacement.
      We looked for independent factors predicting overall survival. RESULTS: Overall
      survival tended to be better after conservative mitral surgery, reaching 86% at 4
      years versus 72% after replacement (p = 0.08). The populations were different as
      the valve replacement group included more women, was more symptomatic (p =
      0.022), had heart failure more often (p = 0.003) and tended to have a higher
      French score (p = 0.06). Inversely, the hemodynamic and echocardiographic
      parameters were not different between the two groups. DISCUSSION: Independent
      factors predicting late mortality were preoperative heart failure and the French
      score. The type of mitral surgery did not have any predictive value. CONCLUSION:
      In addition to its value for assessing operative risk, the French score appears
      to be useful for predicting overall survival after mitral surgery.

PMID- 9246100
TI  - [Catheter infection in intensive care: influence of systematic replacement of
      central venous catheters on a guide wire every 4 days].
AB  - OBJECTIVES: Determine whether systematic replacement of central venous catheters
      on a guide wire every 4 days leads to a lower rate of catheter infection.
      METHODS: We conducted a prospective randomized study comparing systematic
      catheter replacement with the standard procedure where one-way catheters are left
      in situ as needed. RESULTS: The study included 150 patients and 170 catheters.
      Catheter replacement on a guide wire was performed 169 times. The rate of
      infection was not significantly different between the group of patients with
      replacement (3.7 for 1000 catheter days) and the group with systematic
      replacement (5.4 for 1000 catheter days). No mechanical complications occurred
      during the replacement procedures on guide wires. CONCLUSION: We do not recommend
      systematically replacing catheters on a guide wire for the prevention of catheter
      infection. This procedure may however be indicated in case of suspected catheter
      infection as no mechanical of infectious complications occurred.

PMID- 9246101
TI  - [Postpartum thyroiditis and Basedow disease].
AB  - BACKGROUND: The postpartum period is characterized by a rebound in autoimmunity
      secondary to immune tolerance induced by pregnancy, creating favorable conditions
      for flare up of Graves' disease or autoimmune thyroiditis. Postpartum thyroiditis
      is a recognized clinical entity. CASE REPORT: Six years after onset of Graves'
      disease treated with antithyroid drugs, a 25-year-old woman had a high serum
      level of antithyroperoxidase antibodies a few months before she became pregnant.
      Six weeks after delivery, she developed signs of hyperthyroidism and goiter. The
      diagnosis of postpartum thyroiditis was retained. Her condition regressed
      spontaneously to euthyroidism then hypothyroidism. DISCUSSION: The therapeutic
      options involved underline the importance of distinguishing between Graves'
      disease and postpartum thyroiditis. The diagnosis of postpartum thyroiditis is
      based on history taking, clinical findings, and laboratory tests, especially
      isotope uptake.

PMID- 9246102
TI  - [Aspergillus niger osteitis of the middle ear in a patient with HIV infection].

PMID- 9246103
TI  - [Nocardia nova pulmonary infection under treatment with fludarabine].

PMID- 9246105
TI  - [Search for Cys282Tyr mutation in porphyria cutanea tarda].

PMID- 9246104
TI  - [Hypoglycemia during renutrition].

PMID- 9246106
TI  - [Pulmonary transplantations. Current assessment].
AB  - After fifteen years of experience, 3-year survival rates after lung
      transplantation have reached 60% for heart-lung, two-lung and single-lung
      procedures. At 7 years, the rate is currently 41%. Lung transplantation has thus
      become the ultimate treatment for end-stage respiratory failure, and, as we were
      able to establish in 1988, single lung transplantation is now the indication of
      choice. Most of the early complications after transplantation, including edema
      and post-operative shock, though relatively frequent, can generally be
      controlled. There is however the problem of acute rejection during the first
      three months following transplantation due to herpes or cytomegalovirus
      infections which respond poorly to antiviral therapy. Immunosuppressive therapy
      generally can control acute rejection, but subsequent chronic episodes may
      account for 25% of long-term failures. Episodes of chronic rejection usually
      occur after nine months but onset may be retarded beyond 3 years. The real
      problem today is the small number of donors and the long waiting lists. In
      France, where 200 lung transplantations are needed annually, the number of donors
      is dramatically insufficient.

PMID- 9246107
TI  - [Hodgkin's disease. Role of the Epstein-Barr virus].

PMID- 9246108
TI  - [Hodgkin's disease. Long-term complications of radiotherapy].

PMID- 9246109
TI  - [Hodgkin's disease. Current aspects].

PMID- 9246110
TI  - [Cutaneous larva migrans].

PMID- 9246111
TI  - [Ultrasound-guided pericardial drainage. Experience in 34 consecutive patients].
AB  - OBJECTIVES: Transthoracic echoguided puncture of the pericardium can be an
      alternative to surgical drainage. We report our experience with this technique
      acquired over the last 11 years. PATIENTS AND METHODS: From January 1984 to
      September 1995, 34 consecutive patients in the cardiology intensive care unit
      (mean age 56.5 +/- 13 years) underwent echoguided pericardial puncture for poorly
      tolerated pericardial effusion. The underlying cause was neoplasia (n = 22),
      idiopathic disease (n = 5), autoimmune disease (n = 2), post-surgical
      complication (n = 2 including 1 on hemodialysis), infection (n = 1), antivitamin
      K therapy (n = 1) and disseminated vascular coagulation (n = 1). The subxyphoid
      (n = 33) or left parasternal (n = 1) route was used under echographic guidance.
      Intrapericardial contrast allowed verification of the catheter position. The mean
      quantity of fluid removed was 585 +/- 390 ml. The fluid was hemorrhagic (n = 19),
      clear (n = 10) or serohematic (n = 4). Aspiration was continued in 16 patients
      after the initial puncture for a mean 64 hours. The mean total volume of fluid
      was 750 +/- 330 ml. RESULTS: There was one death during puncture which was found
      to be unrelated to the procedure after anatomic verification. In two cases, the
      left ventride was punctured without any consequence. Collapsus occurred during
      puncture in 2 patients with pulmonary sepsis. Minor incidents were: 6 vasovagal
      syndromes at puncture with paroxysmal supraventricular rhythm disorder during
      aspiration. Prior to 1988, surgical drainage was required in 5 patients for
      persistent or recurrent effusion. Since that time, continuous aspiration has been
      used in all patients and no surgical drainage has been required. Short-term
      prognosis depends on the underlying cause (6 deaths at 1 month). CONCLUSION:
      Echoguided pericardial puncture is a simple procedure which rapidly improves
      cardiac hemodynamics in these particularly fracle patients. Continuous aspiration
      avoids subsequent surgical drainage for persistent or recurrent effusion.

PMID- 9246112
TI  - [Diagnostic value of the HLA phenotype in inflammatory rheumatic diseases].
AB  - OBJECTIVES: HLA phenotyping is usually considered as costly and unnecessary for
      the diagnosis of inflammatory rheumatoid diseases. The aim of our work was to
      assess the diagnostic value of HLA phenotyping compared with the diagnostic value
      of sex and age at the onset of disease in cases where there is a doubt between
      rheumatoid polyarthritis and spondyloarthropathy with peripheral involvement.
      METHODS: The relative prevalence of inflammatory rheumatoid diseases was
      calculated for 138 patients hospitalized for diagnosis of rheumatoid disease. We
      considered however that in these patients the etiology of the inflammatory
      rheumatoid disease with synovitis, after search for etiology, could be either
      spondyloarthropathy with peripheral involvement or early-stage rheumatoid
      polyarthritis. Positive and negative predictive values were calculated by
      comparison between these two diseases. The sensitivity of HLA B27 in
      spondyloarthropathy with peripheral involvement was determined in a population of
      83 hospitalized patients with confirmed diagnosis. The prevalence of HLA DR4 in
      rheumatoid polyarthritis was determined in 375 hospitalized patients with
      confirmed diagnosis. Predictive values were calculated using Bayes formula.
      RESULTS: The analysis of the positive and negative predictive values for HLA B27
      showed that the diagnostic value of this allele was much greater than age at
      disease onset and sex in spondyloarthropathy with peripheral involvement. For
      rheumatoid arthritis, comparison of the diagnostic value of HLA DR4 versus age at
      disease onset and sex showed the lower performance of HLA DR4. However, the
      positive predictive value of HLA DR4 in rheumatoid polyarthritis was similar to
      that for these factors and equivalent to that of HLA B27. The positive predictive
      value for the combinations HLA DR4+ HLA B27- and HLA B27+ HLA DR4- was 0.90 for
      rheumatoid polyarthritis and spondyloarthropathy with peripheral involvement
      respectively. CONCLUSION: The validity of these promising findings should be
      confirmed in prospective studies.

PMID- 9246113
TI  - [Continuous intrathecal injection of baclofen in generalized tetanus. A
      therapeutic alternative].
AB  - BACKGROUND: In France, tetanus is diagnosed predominantly in the elderly due to
      the absence of vaccination in this population. Mortality remains high and is
      mainly related to complications secondary to prolonged hospitalization,
      intravenous administration of benzodiazepines, and at times curares. Baclofen, a
      selective agonist of GABAB receptors, directly counteracts the effects of the
      tetanic toxin. CASE REPORT: We report the case of a 92-year-old man suffering
      from tetanus, who fully recovered after a myorelaxant treatment based solely on
      intrathecal baclofen administration. Continuous intrathecal administration of
      baclofen resulted in a marked muscular relaxation with minor side effects
      (bradycardia, sleepiness), which rapidly stopped after the cessation of the
      treatment. Initial careful titration is required in order to determine the
      optimal dose of baclofen which provides a substantial myorelaxation together with
      minor central effects. Low concentration of baclofen may facilitate its
      diffusion. DISCUSSION: Continuous intrathecal administration of barclofen appears
      to be a valuable alternative therapy in tetanus. This new therapeutic modality
      promises to improve the prognosis of this condition, especially in the elderly.

PMID- 9246114
TI  - [Splenic rupture in a patient with malaria].

PMID- 9246115
TI  - [Beware of tobaccoless cigarettes].

PMID- 9246116
TI  - [Lymph node cryptococcosis in an AIDS patient on long-term fluconazole: relapse
      or cure?].

PMID- 9246117
TI  - [Coma induced by intravenous acyclovir in a hemodialyzed patient].

PMID- 9246118
TI  - [Pericardial drainage. The right indication for the right technique].
AB  - The only valid criterion for comparing surgical (or medical) techniques is the
      extent of the beneficial effect compared with the risk of the underlying disease.
      The paper on echoguided pericardial puncture published in this issue of La Presse
      Medicale offers an excellent opportunity to apply this criterion in an area of
      clinical therapeutics where the temptation to promote "minimally invasive"
      techniques is so great. For pericardial effusion, as for all medical conditions,
      it is the underlying disease which determines the long-term outcome and not the
      pericardial effusion itself, even in emergency situations. The objective should
      then go beyond symptom relief and include, when possible, a search for an
      etiological diagnosis. Pericardial biopsy is one element which can be
      contributive in a significant number of cases further adding to the beneficial
      effect of the surgical technique. Consequently, indications for echoguided
      pericardial puncture cannot be broadened beyond patients suffering from
      compressive pericardial effusion secondary to a perfectly recognized cause. In
      other less urgent situations, and when the etiology has not been identified,
      videoscopic techniques appear to be indicated rather than conventional surgical
      drainage or echoguided puncture. Other cases, such as infected or recurrent
      effusions, also raise specific problems requiring a careful evaluation of the
      expected benefit and risk of each technique. After videosurgery and videoscopy,
      conventional pericardial drainage, a particularly simple, rapid and effective
      procedure, is once again challenged by a new, more "medical" technique,
      emphasizing that the ever renewed story of progress in medicine must not avert
      our attention from the fundamental goal of combating disease.

PMID- 9246119
TI  - [At the Academie Nationale de Medecine. Passive smoking].

PMID- 9246120
TI  - [The 8th human herpesvirus].

PMID- 9246121
TI  - [History and renewal of macrolides].

PMID- 9246122
TI  - [Bolus of corticoids: side-effects and precautions of use].

PMID- 9246123
TI  - [Cancer of the kidney].

PMID- 9246124
TI  - Treating asthma in developing countries: a problem of inaccessible unavailable
      essential medication.

PMID- 9246125
TI  - Provision of asthma medications in developing countries: a view from the
      pharmaceutical industry.

PMID- 9246126
TI  - Premenstrual asthma: still poorly understood.

PMID- 9246127
TI  - Intravenous immunoglobulin therapy for asthma: time for a closer look?

PMID- 9246128
TI  - The role of corticosteroids in bronchiolitis and croup.

PMID- 9246129
TI  - Clinical trials in lung cancer: nihilism versus enthusiasm.

PMID- 9246130
TI  - Is asthma treatment affordable in developing countries?
AB  - BACKGROUND: A study was undertaken to assess whether the therapeutic aspects of
      published international asthma management guidelines are practically applicable
      in developing countries. METHODS: Questionnaires were sent to expatriate doctors
      working in developing countries. RESULTS: Forty one replies were received from 24
      countries in Africa and Asia. Oral salbutamol was prescribed "usually" or "often"
      by 35 of the 41 respondents, theophyllines by 30, inhaled bronchodilators by 12,
      inhaled steroids by two, and cromoglycate by two. Theophyllines were locally
      available in all 41 cases, oral salbutamol in 40, inhaled bronchodilators in 34,
      and inhaled steroids (usually beclomethasone 50 micrograms) in only 15. Where
      they were available, the median (range) coat of a beclomethasone 50 micrograms
      inhaler was 20% (6.8-100%) of average local monthly income, salbutamol inhaler
      13% (3.3-250%), 90 salbutamol 4 mg tablets 3.8% (0.8-75%), and 90 aminophylline
      100 mg tablets 4.5% (0.5-70%). If they were available locally at a cheaper price,
      34 (83%) respondents would prescribe more inhaled steroids and 37 (90%) would
      prescribe more inhaled bronchodilators. CONCLUSIONS: Many asthma patients in
      developing countries are not receiving adequate treatment because the required
      drugs are not available in their area or are prohibitively expensive.

PMID- 9246131
TI  - Loss of normal cyclical beta 2 adrenoceptor regulation and increased premenstrual
      responsiveness to adenosine monophosphate in stable female asthmatic patients.
AB  - BACKGROUND: A study was undertaken to investigate the influence of the menstrual
      cycle on airway responsiveness and beta 2 adrenoceptor function in female
      asthmatic patients. It has previously been shown that normal women exhibit
      cyclical changes in beta 2 adrenoceptor function with an increase in beta 2
      adrenoceptor density in the luteal phase during the premenstrual period. METHODS:
      Fifteen women with stable, well controlled asthma (mean forced expiratory volume
      in one second (FEV1) 2.971 (93.8% predicted)) were evaluated. Measurements were
      made at the follicular phase (days 1-6) and the luteal phase (days 21-24) of the
      menstrual cycle. Airway responsiveness was assessed using adenosine 5'
      monophosphate (AMP) and expressed as PC20 AMP. Beta 2 adrenoceptor function was
      evaluated by measuring lymphocyte beta 2 adrenoceptor parameters and constructing
      dose-response curves to salbutamol (100-1600 micrograms). The levels of female
      sex hormones were also measured at both phases of the cycle. RESULTS: There were
      significant increases in serum levels of both oestradiol (2.2-fold, p < 0.001)
      and progesterone (7.2-fold, p < 0.05) between the follicular and luteal phases.
      Geometric mean PC20 AMP was 19.0 mg/ml and 7.6 mg/ml during the follicular and
      luteal phases, respectively (p < 0.05), a 2.51-fold difference (95% CI 1.19 to
      5.30) amounting to 1.33 doubling doses of AMP. There was no change in lymphocyte
      beta 2 adrenoceptor parameters or in airway beta 2 adrenoceptor responses to
      salbutamol between the two phases. CONCLUSIONS: Despite an appropriate rise in
      female sex hormones during the luteal period, beta 2 adrenoceptor regulation in
      female asthmatic subjects shows a loss of the normal cyclical pattern. In
      addition, there were cyclical changes in airway responsiveness to AMP which was
      highest during the premenstrual period. Thus, drugs such as theophylline which
      block adenosine receptors warrant investigation in premenstrual asthma.

PMID- 9246132
TI  - Drug use and pulmonary death rates in increasingly symptomatic asthma patients in
      the UK.
AB  - BACKGROUND: There is concern about an increase in deaths from respiratory causes
      in asthma patients using long acting beta agonists. According to the guidelines
      of the British Thoracic Society, long acting beta agonists, ipratropium bromide,
      and theophylline should be used to treat patients with increasing asthma severity
      who are already receiving treatment with short acting beta agonists and inhaled
      steroids. A study was therefore undertaken to compare the characteristics and
      short term respiratory mortality rates in first time users of one of these three
      drugs. METHODS: An open cohort study with a nested case-control analysis was
      performed on the UK based General Practice Research Database (GPRD). First time
      users of either salmeterol (n = 8386), ipratropium bromide (n = 4305), or
      theophylline (n = 4228) between 1 January 1992 and 30 April 1995 were identified
      and followed for 16 weeks. Drug usage patterns, predictors for respiratory
      mortality, and the number of deaths at 16 weeks in the three drug groups were
      compared. RESULTS: The three asthma drugs were most often prescribed to patients
      with severe asthma. Age, a concomitant diagnosis of chronic obstructive pulmonary
      disease or emphysema, number of asthma drug prescriptions, number of visits to
      the general practitioner, and whether or not the patient had been admitted to
      hospital due to the respiratory disease in the 12 months prior to the start of
      the new drug therapy were strong predictors for asthma mortality. After adjusting
      for several risk factors, the relative risk estimates of a respiratory death for
      ipratropium bromide and theophylline users compared with salmeterol users were
      1.8 (95% CI 0.4 to 9.6) and 3.0 (95% CI 0.4 to 22.4), respectively. CONCLUSIONS:
      In the UK population studied, salmeterol, ipratropium bromide and theophylline
      are regularly used to treat patients with asthma of increasing severity.
      Salmeterol use was not associated with an increase in short term mortality
      compared with ipratropium bromide and theophylline.

PMID- 9246133
TI  - The home environment and asthma symptoms in childhood: two population based case
      control studies 13 years apart.
AB  - BACKGROUND: Prevalence surveys of asthma and/or wheezing among all children aged
      between 7 1/2 and 8 1/2 attending state and private schools in the London Borough
      of Croydon were conducted in February 1978 and February 1991. Two population
      based case-control studies drawn from the survey responders were used to
      investigate the association between childhood wheeze and characteristics of the
      home environment and to assess whether changes in these characteristics between
      1978 and 1991 may have contributed to an increase in the population prevalence of
      wheeze among school children. METHODS: Information on exposure to potential
      indoor environmental risk factors was obtained from parents by home interview and
      compared between cases-that is, children with frequent (> or = 5) or in-frequent
      (1-4) attacks of asthma or wheezing in the past 12 months- and controls, with
      adjustment for study. Changes in exposure over time were assessed by comparing
      control groups. RESULTS: Between 1978 and 1991 the population prevalence odds of
      wheeze increased by 20% (OR 1.20; 95% CI 1.04 to 1.39). Change in parental
      smoking, gas cooking, pet ownership, and central heating did not appear to
      explain the rise. Use of non-feather pillows was positively associated with
      childhood wheeze even after adjusting for other risk factors and after re-coding
      from non-feather to feather cases thought to have changed pillow in response to
      symptoms (OR 1.54; 95% CI 1.13 to 2.10). The proportion of control children
      reportedly using non-feather pillows was 44% in 1978 and 67% in 1991.
      CONCLUSIONS: Increased use of non-feather pillows was the only domestic indoor
      exposure studied which appeared to explain a modest rise in prevalence of wheeze
      from 1978 to 1991. Our analysis attempts to address behavioural change in
      response to the child's symptoms but an artifact arising from lifelong avoidance
      of feather bedding in atopic families cannot be entirely discounted.

PMID- 9246134
TI  - Endothelin-1 levels in induced sputum samples from asthmatic and normal subjects.
AB  - BACKGROUND: Endothelin-1 (ET-1) is a potent bronchoconstrictor which may have a
      role in the pathogenesis of asthma. The levels of ET-1 in saliva, induced sputum,
      and plasma from asthmatic and non-asthmatic subjects were compared. METHODS:
      Sputum induction was performed on 28 asthmatic subjects and nine normal
      volunteers. ET-1 levels were measured in plasma, saliva, and sputum samples and
      reversed phase high performance liquid chromatography (RP-HPLC) was performed on
      saliva and sputum samples. RESULTS: ET-1 was present in the following order of
      concentration in both normal and asthmatic subjects: saliva > sputum > plasma
      (saliva, median 30.1 and 23.9 pg/ ml, respectively; sputum, median 15.5 and 11.2
      pg/ml; plasma, median 3.1 and 3.6 pg/ ml). There were no differences between
      asthmatic and normal subjects in the levels of ET-1 in each fluid. The levels of
      ET-1 in asthmatic subjects were not influenced by whether or not they were taking
      inhaled steroids. RP-HPLC of sputum and saliva confirmed the presence of ET-1 in
      these fluids. CONCLUSIONS: Levels of ET-1 can be measured in saliva and sputum
      obtained by sputum induction in asthmatic and healthy subjects and, although no
      difference was found in basal levels of ET-1 in sputum, saliva and plasma between
      normal subjects and asthmatics without bronchoconstriction, it is apparent that
      ET-1 is produced or released locally within the respiratory tract in
      concentrations higher than those in plasma.

PMID- 9246135
TI  - Effect of fresh fruit consumption on lung function and wheeze in children.
AB  - BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated
      with improved lung function in adults. Whether this is due to enhancement of lung
      growth, to a reduction in lung function decline, or to protection against
      bronchospasm is unclear. METHODS: In a cross-sectional school based survey of
      2650 children aged 8-11 from 10 towns in England and Wales the main outcome
      measure was forced expiratory volume in one second (FEV1) standardised for body
      size and sex. Exposure was assessed by a food frequency questionnaire to parents
      and by measurement of plasma levels of vitamin C in a subsample of 278 children.
      RESULTS: FEV1 was positively associated with frequency of fresh fruit
      consumption. After adjustment for possible confounding variables including social
      class and passive smoking, those who never ate any fresh fruit had an estimated
      FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day
      (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was
      stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference
      in trend), though wheeze itself was not related to fresh fruit consumption.
      Frequency of consumption of salads and of green vegetables were both associated
      with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin
      C levels were unrelated to FEV1 (r = -0.01, p = 0.92) or to wheeze and were only
      weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS:
      Fresh fruit consumption appears to have a beneficial effect on lung function in
      children. Further work is needed to confirm whether the effect is restricted to
      subjects who wheeze and to identify the specific nutrient involved.

PMID- 9246136
TI  - Randomised double blind placebo controlled trial of prednisolone in children
      admitted to hospital with respiratory syncytial virus bronchiolitis.
AB  - BACKGROUND: Experimental and clinical evidence suggests that respiratory
      syncytial virus (RSV) bronchiolitis is an immune mediated disease.
      Corticosteroids might therefore be effective in the treatment of RSV
      bronchiolitis. METHODS: A randomised double blind trial was conducted in children
      up to two years of age admitted to hospital with RSV bronchiolitis to compare
      prednisolone (1 mg/ kg/day orally for seven days) with placebo. Variables used
      for the efficacy analysis were a daily symptom score and the length of time in
      hospital in the non-ventilated patients, and the duration of mechanical
      ventilation and the length of time in hospital in the ventilated patients.
      RESULTS: Fifty four patients were included in the trial, 40 of whom were non
      ventilated (20 in each group) and 14 were ventilated (seven in each group).
      During the first three days of treatment the symptom score decreased
      significantly faster in the prednisolone group than in the placebo group (mean
      (SE) decrease -1.2 (0.2) points/day versus -0.6 (0.2) points/day; mean (95%
      confidence interval (CI)) for difference = -0.6 (-0.1 to -1.2); p = 0.02). The
      mean duration of hospital stay of all 40 non-ventilated patients was not
      significantly different between the two groups. In the ventilated patients the
      duration of mechanical ventilation was not significantly different, but the
      length of time in hospital was six days shorter in the prednisolone group than in
      the placebo group (mean (SE) 11.0 (0.7) versus 17.0 (2.0) days; mean (95% CI)
      difference = 7.0 (1.8 to 10.2) days; p < 0.01). CONCLUSIONS: These results
      suggest that prednisolone may be effective in accelerating the clinical recovery
      of children admitted to hospital with RSV bronchiolitis.

PMID- 9246137
TI  - Effect of exposure to swine dust on levels of IL-8 in airway lavage fluid.
AB  - BACKGROUND: Inhalation of swine dust causes airway inflammation with influx of
      inflammatory cells, predominantly neutrophils, into the lungs. A study was
      undertaken to determine whether or not exposure to swine dust induces release of
      interleukin 8 (IL-8) into upper and lower airways and how this possible release
      is related to cellular influx. A further aim was to study the relationship
      between the inflammatory response and swine dust exposure. METHODS: Thirty one
      healthy, non-smoking, previously unexposed subjects were exposed to swine dust
      during three hours work in a swine house. Bronchoalveolar lavage (BAL) was
      performed two weeks before and 24 hours after the exposure (n = 16). Nasal lavage
      and acoustic rhinometry were carried out 1-2 hours before and seven hours after
      the start of the exposure (n = 31). Exposure measurements were performed with
      personal sampling equipment. RESULTS: The exposure led to 19-fold and 70-fold
      increases in the neutrophil concentrations in nasal lavage and BAL fluid,
      respectively (p < 0.001). In BAL, fluid macrophages, lymphocytes and eosinophils
      increased significantly. The IL-8 levels in BAL fluid increased from < 31.3 ng/l
      to 63 (43-109) ng/l (median (25-75th percentile), p < 0.001), and in nasal lavage
      fluid the concentrations increased from 144 (97-227) ng/l to 1064 (864-1437) ng/l
      (p < 0.001). IL-8 levels showed a significant correlation with the increase in
      neutrophils in the nasal lavage fluid but not in the BAL fluid. Acoustic
      rhinometry demonstrated significant swelling of the nasal mucosa. The air
      concentration of inhalable dust was 23.3 (20.0-29.3) mg/m3, endotoxin 1.3 (1.1
      1.4) micrograms/m3, and muramic acid 0.99 (0.78-2.1) microgram/m3. CONCLUSIONS:
      The concentration of IL-8 increases in BAL fluid and nasal lavage fluid following
      exposure to swine dust and may be one of the chemoattractants contributing to the
      recruitment of neutrophils to the nasal cavity and the alveolar space.

PMID- 9246138
TI  - Role of pulmonary function in the detection of allograft dysfunction after heart
      lung transplantation.
AB  - BACKGROUND: Lung function is altered by infection and rejection in patients who
      undergo heart-lung transplantation. The sensitivity, specificity, and
      positive/negative predictive values (PPV and NPV) of lung function for the
      detection of allograft dysfunction in these patients were measured. METHODS:
      Thirty three patients who underwent heart-lung transplantation were followed for
      a mean period of 16.3 months. On 123 occasions functional measurements were
      obtained at the time a transbronchial biopsy specimen and/or bronchoalveolar
      lavage fluid was taken, which were used as gold standards. Optimal sensitivity
      (the value for which sensitivity equals specificity) was computed for each
      functional test from receiver-operator characteristic (ROC) curves. RESULTS:
      Acute rejection was present on 31 occasions and infection on 36 occasions; 56
      samples were normal. Infection and rejection were accompanied by airflow
      obstruction, a rise in the slopes of the alveolar plateaus for nitrogen,
      hexafluoride sulphur and helium (SN2, SSF6, and SHe), and a decrease in the
      difference between SSF6 and SHe (delta S), total lung capacity (TLC), and lung
      transfer factor (TLCO). Optimal sensitivities for SHe, mid forced expiratory flow
      (FEF25-75), TLC, and forced expiratory volume in one second (FEV1) were 68%, 67%,
      66%, and 60%, respectively; they were not different for infection and rejection
      and did not change over the study period. For infection and rejection together,
      PPV ranged from 72% to 88% and NPV from 27% to 52% according to the functional
      test and the postoperative period considered. CONCLUSIONS: Indices of ventilation
      distribution, FEF25-75, and TLC have the best optimal sensitivity for the
      diagnosis of infection and rejection after heart-lung transplantation. The high
      PPV of pulmonary function in detecting allograft dysfunction observed in this
      study suggests that a diagnostic procedure should be performed whenever one or
      more functional tests deteriorate; conversely, the low NPV indicates that a
      stable pulmonary function does not rule out allograft dysfunction.

PMID- 9246139
TI  - Effects of nasal CPAP on simulated driving performance in patients with
      obstructive sleep apnoea.
AB  - BACKGROUND: Many patients with obstructive sleep apnoea (OSA) have difficulty in
      driving and experience increased automobile accidents. It has previously been
      shown that patients with OSA perform poorly on a laboratory based divided
      attention driving test (DADT). METHODS: Seventeen men with OSA of mean (SD) age
      49.7 (11.2) years and an initial apnoea/hypopnoea index (AHI) of 73.0 (28.9) were
      restudied from one to 12 (mean (SD) 9.2 (4.2)) months after initiating treatment
      with nasal continuous positive airway pressure (CPAP) to examine the effects of
      treatment on DADT performance. Eighteen age and sex matched controls were also
      retested 8.4 (3.4) months after their initial tests. Following a practice
      session, all subjects were given the DADT for 20 minutes before each daytime nap
      of the standard multiple sleep latency test (MSLT). RESULTS: Untreated patients
      with OSA, who performed much worse than controls in all measures, improved
      significantly on all measures of performance, particularly in tracking error
      which returned to the level of controls in all but one patient. Changes in
      performance were much greater for patients with OSA than for controls in tracking
      error (mean difference 106 (95% CI 75 to 135) cm), sleep latency/ MSLT (5.3 (95%
      CI 2.7 to 8.0) min), number of correct responses (1.2 (95% CI 0.4 to 1.9)),
      number of missed responses (1.7 (95% CI 0.9 to 2.3)), and number out of bounds
      (10.0 (95% CI 7.9 to 13.6)), but not for response time (0.1 (95% CI -0.3 to 0.2)
      s). Improvement in tracking error was highly correlated with improvement in
      sleepiness (r = 0.65). CONCLUSIONS: Impairment in laboratory driving performance
      skills in patients with OSA is reversed by successful treatment with nasal CPAP.
      Changes in daytime sleepiness account for some but not all of the improvement.

PMID- 9246140
TI  - Atopy phenotype in subjects with variants of the beta subunit of the high
      affinity IgE receptor.
AB  - BACKGROUND: Fc epsilon RI plays a central role in atopy, thus genetic variants of
      Fc epsilon RI-beta may alter receptor function to enhance atopic responses and
      may manifest as a more severe atopic phenotype and more symptomatic atopic
      disease. The immunological and clinical features of atopy in children with and
      without the Leu 181 variant of Fc epsilon RI-beta were compared. METHODS: Sixty
      British nuclear families, including 10 families with the Fc epsilon RI-beta
      variant Leu 181, recruited via a young proband with atopic asthma were analysed
      for atopic parameters including total IgE, specific IgE, and clinical atopic
      disorder. RESULTS: Compared with other children (combined atopic and non-atopic
      subjects), maternally inherited Leu 181 was associated with increased levels of
      total IgE (odds ratio (OR) 4.82, 95% confidence interval (CI) 1.02 to 27.66, p <
      0.01) and a positive IgE response to grass pollen allergen (OR 7.45, 95% CI 1.56
      to 35.52, p < 0.005) but not wheeze (OR 1.97, 95% CI 0.56 to 7.69), asthma (OR
      2.25, 95% CI 0.65 to 7.85), or required medications (OR 0.95, 95% CI 0.29 to
      3.14). There were trends for each atopic parameter to be more marked in atopic
      children with maternally inherited Leu 181 than in atopic children without Leu
      181. Children with maternal Leu 181 had significantly raised eosinophils but
      there was no difference in basophil levels compared with other atopic children.
      CONCLUSIONS: The Leu 181 variant of Fc epsilon RI-beta, or another identified
      variant in linkage disequilibrium, may promote the development of atopy.

PMID- 9246141
TI  - Effect of tonicity of nebulised colistin on chest tightness and pulmonary
      function in adults with cystic fibrosis.
AB  - BACKGROUND: Inhalation of hypertonic nebulised colistin causes chest tightness
      and is a reason for discontinuing the treatment. This study examines the
      relationship of chest tightness and change in lung function in response to the
      inhalation of a range of tonicities of nebulised colistin and their influence on
      patients' preference. METHODS: Twenty seven adult patients with cystic fibrosis
      and a mean forced expiratory volume in one second (FEV1) of 54% predicted (range
      24-98) were studied. They inhaled a nebulised solution of hypertonic, isotonic,
      and hypotonic colistin over three consecutive days in random order in a double
      blind fashion. Measurements of chest tightness, using a visual analogue scale
      (VAS), and FEV1 were recorded before and 0, 15, 30, 60, and 90 minutes following
      inhalation. The solution preferred by each patient was determined at the end of
      the three days. RESULTS: All tonicities caused a significant fall in FEV1 %
      predicted and an increase in chest tightness, with no differences between the
      solutions. However, the mean (SE) time to the maximum fall in FEV1 % predicted
      was significantly different between the solutions (hypertonic 7.8 (2.1) min,
      isotonic 19.2 (5.5) min, and hypotonic 34.2 (5.9) min) with a mean difference
      (95% CI) between hypotonic and hypertonic solutions of 28.04 (14.6 to 41.5) min,
      between isotonic and hypertonic solutions of 12.0 (-0.1 to 24.1) min, and between
      hypotonic and isotonic solutions of 15.6 (1.8 to 29.4) min. Positive correlations
      existed for the maximum fall in FEV1 % predicted between the hypertonic and
      isotonic solutions (r = 0.62, p < 0.001) and between the hypotonic and isotonic
      solutions (r = 0.64, p < 0.001). There was no correlation between the objective
      and subjective measurements for any solution. The patients' preference varied.
      CONCLUSIONS: All tonicities of colistin caused equal symptoms of chest tightness
      and reduction in pulmonary function. It is recommended that the patient is
      challenged with nebulised colistin before prescription of the drug and that the
      challenge is preceded by an inhaled bronchodilator. Most of the patients
      preferred the isotonic or hypotonic solutions. The isotonic solution reflects a
      fall in FEV1 representative of all the solutions. The fall in FEV1 to the
      hypotonic solution occurred over a longer period and may be better tolerated by
      some patients.

PMID- 9246142
TI  - PI SZ phenotype in chronic obstructive pulmonary disease.
AB  - BACKGROUND: A study was undertaken to clarify whether the PI SZ phenotype of the
      protease inhibitor system predisposes to chronic obstructive pulmonary disease
      (COPD). METHODS: The prevalence of PI Z and PI SZ deficient phenotypes was
      investigated in a population of 702 patients with COPD followed up at the Chest
      Unit of a tertiary hospital and in 15400 newborn infants from the same
      geographical area. Individuals with deficiency were detected by screening of
      dried blood spots on filter paper using a comparative electro-immunodiffusion
      technique for alpha 1-antitrypsin and transferrin. The serum phenotype was
      confirmed by means of isoelectrofocusing on polyacrylamide gel. RESULTS: Of the
      702 blood samples from patients with COPD, six PI Z subjects (0.85%) and one PI
      SZ (0.14%) were detected. Of the 15400 samples from neonates, the number of PI Z
      subjects was eight (0.052%) and that of PI SZ was 24 (0.156%). The difference
      between the two groups was significant for PI Z but not for PI SZ. CONCLUSIONS:
      The data do not indicate an increased risk for development of COPD associated
      with the PI SZ phenotype but confirm the predisposition of PI Z individuals for
      the development of COPD.

PMID- 9246144
TI  - Airway Wallstent.

PMID- 9246143
TI  - Effects of high dose intravenous immunoglobulin in two severe corticosteroid
      insensitive asthmatic patients.
AB  - Preliminary observations of the clinical efficacy of intravenous immunoglobulin
      in two patients with severe corticosteroid insensitive asthma are reported. In
      both patients treatment with intravenous immunoglobulin resulted in clinical
      improvement and enabled a significant reduction in the dose of prednisolone. In
      one of the patients fibreoptic bronchoscopy with endobronchial biopsies was
      performed and peripheral blood was analysed by flow cytometry before and after
      treatment. Immunohistological analysis of the biopsy samples after treatment
      showed a decrease in the number of all cell types, especially CD3+ T cells, CD4+
      T cells, and activated CD25+ T lymphocytes, which was associated with a reduction
      in peripheral blood T cell activation. Intravenous immunoglobulin may be a valid
      option for the treatment of corticosteroid insensitive asthma. To elucidate the
      role and mode of action of intravenous immunoglobulin further studies in larger
      groups of patients are needed.

PMID- 9246145
TI  - Asthma guidelines.

PMID- 9246146
TI  - Asthma guidelines.

PMID- 9246147
TI  - Asthma guidelines.

PMID- 9246148
TI  - Asthma guidelines.

PMID- 9246149
TI  - Oral ondansetron 8 mg twice daily is as effective as 8 mg three times daily in
      the prevention of nausea and vomiting associated with moderately emetogenic
      cancer chemotherapy. S3A-376 Study Group.
AB  - The efficacy and safety of ondansetron 8 mg BID compared with 8 mg TID for 3 days
      in the prevention of nausea and vomiting in 402 patients on cyclophosphamide (>
      or = 500 mg/m2)-based chemotherapy were evaluated in a multicenter, randomized,
      double-blind, stratified study. The percentage of patients with no emetic
      episodes over the 3-day study period was 61% in the ondansetron BID group
      compared with 58% in the ondansetron TID group. Among patients with at least one
      emetic episode, the mean time to emesis was 14 hr and 17 min in the ondansetron
      BID group compared with 12 hr and 48 min in the ondansetron TID group. Patients'
      daily appetite ratings and nausea scores were not significantly different between
      groups. Clinical laboratory and adverse event profiles were similar between
      groups. This study is the first large-scale, double-blind trial to demonstrate
      that ondansetron 8 mg BID for 3 days, a dosing regimen that may enhance patient
      convenience and compliance, is as effective as ondansetron 8 mg TID for 3 days in
      the prevention of nausea and vomiting associated with cyclophosphamide-based
      chemotherapy.

PMID- 9246150
TI  - A double-blind, randomized study of two different dosage regimens of intravenous
      dolasetron in patients receiving high-dose cisplatin chemotherapy.
AB  - This study compared the antiemetic efficacy and safety of two different
      intravenous (i.v.) dolasetron dosing regimens in patients receiving their first
      course of high-dose (> or = 80 mg/m2) cisplatin. Of 30 patients enrolled, 14
      received a single i.v. dolasetron dose (0.6 mg/kg) before cisplatin and 16
      received a multiple i.v. dose regimen (0.6 mg/kg x 3) given before and after
      cisplatin. Complete plus major responses were achieved by 71% (10/14) of patients
      who received single-dose dolasetron and by 50% (8/16) of those who received the
      multiple-dose regimen. Forty-three percent (6/14) of patients who received the
      single dose had a complete response compared with 25% (4/16) who received
      multiple doses. Multiple doses resulted in less nausea at 24 hr following
      cisplatin; however, differences were not statistically significant. Both regimens
      were well tolerated, with mild headache (33%) and diarrhea (13%) the most common
      adverse events. This study demonstrated that a single 0.6-mg/kg dose of
      dolasetron given before chemotherapy provides equivalent antiemetic efficacy to
      three 0.6-mg/kg doses given before and after high-dose cisplatin chemotherapy;
      thus, there was no additional antiemetic benefit by using the multiple-dose
      regimen.

PMID- 9246151
TI  - A phase II trial of deferoxamine in patients with hormone-refractory metastatic
      prostate cancer.
AB  - The management of hormone-refractory metastatic prostate cancer remains a
      therapeutic dilemma. We report the results of a phase II trial with deferoxamine
      administrated at a dose of 50 mg/kg (maximum dose 5 g) administered intravenously
      over 8 hr daily, repeated for 5 days at 4-week intervals for 2 courses. Fourteen
      patients with advanced hormone-refractory prostate cancer were treated and 28
      courses were delivered. Essentially no toxicity was observed. Using combined
      clinical and prostate-specific antigen (PSA) criteria. 13 of 14 patients had
      disease progression. However, 9 of 14 patients had stable measurable or evaluable
      disease and progressed solely based on PSA criteria. Deferoxamine in this dose
      and schedule has no activity in hormone-refractory prostate cancer. Further
      investigation of the effect of deferoxamine on PSA production/expression is
      warranted.

PMID- 9246153
TI  - Introduction to molecular genetics.

PMID- 9246154
TI  - Serum tumor necrosis factor for monitoring response of hepatic veno-occlusive
      disease to pentoxiphyllin--a case report.
AB  - Hepatic veno-occlusive disease (VOD) is the second most common cause of death
      after autologous bone marrow transplantation (ABMT). A patient with multiple
      myeloma undergoing ABMT developed classic features of hepatic VOD. He responded
      to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed
      remarkable correlation with the severity of VOD and response to therapy.

PMID- 9246152
TI  - Phase II trial of topotecan in malignant melanoma.
AB  - Topotecan (S-9-dimethyl-10-hydroxycamptothecin hydrochloride SKF 104864-A) is a
      semisynthetic analog of the alkaloid camptothecin and, similar to the parent
      compound, a potent inhibitor of topoisomerase I. The cytotoxicity induced by
      topotecan appears due to interference with the normal breakage reunion reaction
      of topoisomerase I leading to DNA damage and cell death. Since preclinical
      studies of topotecan suggested antitumor activity against refractory solid
      tumors, a phase II trial of the drug was initiated in melanoma patients with
      recurrent and/or metastatic disease. Topotecan 1.5 mg/m2 was given as a daily 30
      min infusion for 5 days and repeated every 21-28 days. Seventeen patients were
      entered into the treatment program with all evaluable for toxicity but I patient,
      inevaluable for response. There were no objective responses. Toxicity was
      predominantly severe myelosuppression, which occurred in 12 of 17 (70%) patients.
      Topotecan in this dose and schedule is inactive in malignant melanoma.

PMID- 9246155
TI  - Activity of anthracyclines in refractory ovarian cancer: recent experience and
      review.

PMID- 9246157
TI  - The biological therapy of acute and chronic leukemia.
AB  - With the increasing knowledge of the mechanisms of immune-mediated cytotoxicity,
      immunotherapeutic strategies are rapidly being incorporated into chemotherapy
      treatment schemes for acute and chronic leukemias. This includes the use of mAbs,
      immunotoxins, tumor-specific T cells, and, most recently, vaccines. Much of the
      new information is derived from bone marrow transplant data, where immune
      enhancement from IL-2 and donor T-cell infusions are being studied. Trials using
      humanized mAbs that permit prolonged and repeated dosing will allow better
      evaluation of the effectiveness of mAb therapy. More sophisticated molecular
      tests have been developed, allowing the detection of minimal residual disease to
      a greater degree. It is likely that biological and immunological therapy of
      leukemia will have its greatest impact here.

PMID- 9246156
TI  - Treatment of metastatic breast cancer--economic and ethical considerations.

PMID- 9246158
TI  - The role of granulocyte colony-stimulating factor in hematopoietic stem cell
      transplantation.
AB  - Recombinant granulocyte colony-stimulating factor (G-CSF) has been shown to
      decrease the duration of severe neutropenia, the incidence of febrile neutropenic
      episodes, the overall duration of intravenous antibiotic therapy, and the length
      of hospitalization in patients receiving myelosuppressive chemotherapy. G-CSF has
      also been shown to accelerate myeloid recovery after autologous and allogeneic
      bone marrow transplantation, and to mobilize stem cells in peripheral blood for
      hematopoietic rescue. However, the optimal dose, schedule, and method of
      administration of G-CSF in these settings remain to be standardized. This review
      focuses on the role of G-CSF in bone marrow and peripheral blood stem cell
      transplantation, and in hematopoietic stem cell mobilization.

PMID- 9246159
TI  - Regrowth resistance as a likely significant contributor to treatment failure in
      drug-sensitive neoplastic diseases.
AB  - Attempts to improve the effectiveness of therapy for neoplastic diseases have
      largely focused on increasing the cytotoxic efficacy of therapy. While this
      approach is logical, there is another approach, based on the concept of regrowth
      resistance, which offers an alternate means of improving treatment outcome. The
      term "regrowth resistance" refers to the reduction in treatment efficacy
      resulting from the regrowth of neoplastic cells between courses of therapy or
      even between doses of radiation therapy. Regrowth resistance is likely to play a
      significant role in determining the outcome of treatment in rapidly proliferating
      neoplasms. A reduction in the rate of tumor regrowth would increase the net
      effectiveness of cytotoxic therapy and would also inhibit the development of
      resistance to cytotoxic therapies.

PMID- 9246160
TI  - Management of stage IIIB breast cancer.

PMID- 9246162
TI  - Flow cytometry is becoming an indispensable tool in leukemia diagnosis and
      classification.

PMID- 9246161
TI  - Perspective: the chemotherapeutic relevance of apoptosis and a proposed
      biochemical cascade for chemotherapeutically induced apoptosis.

PMID- 9246163
TI  - Flow cytometry: recent advances in diagnosis and monitoring of leukemia.

PMID- 9246164
TI  - Stump the experts. A classic example of a large nodular trichoblastoma.

PMID- 9246165
TI  - The use of the frequency-doubled Q-switched Nd:YAG laser in the treatment of
      small cutaneous vascular lesions.
AB  - BACKGROUND AND DESIGN: The frequency-doubled Q-switched, neodymium:yttrium
      aluminum-garnet (FD QSNd:YAG) laser has proven to be safe and effective in
      treating cutaneous pigmented lesions and tattoos. The observance of purpura
      following FD QSNd:YAG laser treatment of epidermal pigmented lesions led us to
      evaluate the use of this laser in the treatment of vascular lesions. The
      treatment protocol was designed to assess the efficacy of the FD QSNd:YAG laser
      in the treatment of small cutaneous vascular lesions such as telangiectases and
      small angiomas. The FD QSNd:YAG laser (532 nm, 3-mm spot size, and 5-10
      nanosecond pulse width) at 1-2 J/cm2 and 3-4 J/cm2 was used on two comparable
      cutaneous vascular lesions on the skin of each subject. Patients were treated
      once, with follow-up at 1-, 2-, and 6-month intervals, to examine both clinical
      improvement as well as potential adverse sequelae. RESULTS: Lesions treated with
      the FD QSNd:YAG laser at both 1-2 J/cm2 and at 3-4 J/cm2 were improved.
      Statistically greater improvement was achieved when the FD QSNd:YAG laser was
      used at 3-4 J/cm2. CONCLUSIONS: Clinical improvement of small cutaneous vascular
      lesions is possible with the FD QSNd:YAG laser.

PMID- 9246166
TI  - Correlation between the histopathology and the epiluminescence microscopy
      features of malignant blue nevus.
AB  - BACKGROUND: The validation of epiluminescence microscopy (ELM) for the diagnosis
      of pigmented skin lesions is conditional on the demonstration of consistent
      histologic correlates of the ELM patterns. The ELM characteristics of malignant
      blue nevus (MBN) have never been reported previously. OBJECTIVE: To evaluate the
      histologic counterparts of the ELM features of a case of MBN. METHODS: Comparison
      between the histologic characteristics observed in step-sections of the lesion
      and the structures observed in a digital ELM image. RESULTS: On ELM, the lesion
      showed a diffuse whitish-blue veil, round black blotches, a collection of dark
      colored punctate spots, and fragmented bluish reticular-like formations in the
      periphery. At histologic examination, the black blotches and the spots appeared
      to correlate with areas of intense focal necrosis in the papillary and reticular
      dermis, and the reticular-like structures were demonstrated to correspond to the
      presence of free melanin and melanophages in the papillary dermis. CONCLUSION: In
      this case of MBN, blotches and spots seen on ELM correlated with intense necrosis
      in the papillary and reticular dermis, and reticular-like formations were the
      counterparts of free melanin and melanophages in the papillary dermis.

PMID- 9246167
TI  - Frontonasal flap for reconstruction of complete alar defects.
AB  - BACKGROUND: It is difficult to reconstruct a satisfactory ala. Axial frontonasal
      flap has been common in reconstruction of nasal tip. We modified this flap to
      reconstruct nasal ala. OBJECTIVE: A modified axial frontonasal flap was applied
      for reconstruction of complete unilateral alar defects in two patients. METHODS:
      Skin from an intact nasal tip covered the alar defect. The resulting defect in
      the nasal tip was covered with dorsal skin from the nose. Extended mucosa or a
      hinged nasolabial flap was used to line the mucosal side of the reconstructed
      ala. RESULTS: The outcome judged by shape, and texture, was satisfactory. This
      technique can be employed under field block. CONCLUSION: The modified frontonasal
      flap is one of the ideal techniques to reconstruct an entire nasal ala.

PMID- 9246168
TI  - Cryosurgery in the treatment of basal cell carcinoma. Assessment of one and two
      freeze-thaw cycle schedules.
AB  - BACKGROUND: It has become routine practice in many centers to use two successive
      freeze-thaw cycles in the treatment of the common types of basal cell carcinoma.
      Because of the potential morbidity caused by this, we have investigated the cure
      rate achieved with one freeze-thaw cycle compared with that achieved with two
      freeze-thaw cycles in the treatment of facial basal cell carcinomas of a uniform
      type and clinically in the best prognostic group. Superficial truncal basal cell
      carcinomas are reported to respond to less aggressive cryosurgery, and we have
      investigated the cure rate achieved with one freeze-thaw cycle. OBJECTIVE: To
      compare the efficacy of one freeze-thaw cycle versus two freeze-thaw cycles in
      the treatment of facial basal cell carcinomas. Second, to investigate the
      efficacy of one freeze-thaw cycle in the treatment of superficial truncal basal
      cell carcinomas. This was investigated in a prospective randomized post-treatment
      follow-up study. METHODS: Over the past 7 years, we have treated 84 facial basal
      cell carcinomas with either a single 30-second freeze-thaw cycle or a double 30
      second freeze-thaw cycle. Patients were allocated randomly into one of the two
      treatment schedules, and the cure rates achieved were compared. Second, 29
      superficial truncal basal cell carcinomas were treated with a single 30-second
      freeze-thaw cycle. Patients were followed up to assess response to therapy.
      RESULTS: A 95.3% cure rate was achieved in the treatment of facial basal cell
      carcinomas with a double freeze-thaw cycle. This compared with a cure rate of
      only 79.4% when facial lesions were treated with a single freeze-thaw cycle.
      Treatment of superficial truncal basal cell carcinomas with a single freeze-thaw
      cycle achieved a cure rate of 95.5%. CONCLUSION: We recommend that, in order to
      achieve high cure rates that are equivalent to many reports of formal excision or
      radiotherapy, facial basal cell carcinomas require a double freeze-thaw cycle
      with liquid nitrogen. One freeze-thaw cycle to truncal basal cell carcinomas
      achieves high cure rates, equal to that achieved with a double freeze-thaw cycle
      to facial basal cell carcinomas.

PMID- 9246169
TI  - Penetration depth of Ultrapulse carbon dioxide laser in human skin.
AB  - BACKGROUND: Recent technological advances have dramatically increased the use of
      lasers in skin resurfacing. The first high-power short-pulse laser, Ultrapulse,
      has found extensive use in dermatology and plastic surgery for skin resurfacing.
      Reports for penetration depth are at best anecdotal. To our knowledge this is the
      first report of histological effects of the Ultrapulse in human skin. OBJECTIVE:
      To determine the effect of single and repeated (two or three) Ultrapulse laser
      impacts on volar forearm skin. METHOD: The volar surface of the arm in four
      patients received in adjacent areas either one, two, or three pulses, after
      anesthesia. The treated areas were immediately biopsied, hematoxylin & eosin
      prepared, and examined. RESULTS: Increasing the number of passes correlates with
      increased depth of penetration and thermal ablation. No significant propagation
      of destructive thermal energy to adjacent tissue was noted. CONCLUSION: One
      impact at the tested parameters ablated most of the epidermis. Two impacts
      superimposed ablated the entire epidermis and the superficial papillary dermis.
      Three superimposed impacts penetrated to the reticular dermis.

PMID- 9246170
TI  - Effects of medical elastic compression stockings on interface pressure and edema
      prevention.
AB  - BACKGROUND: Although medical elastic compression stockings are widely used in
      venous diseases their effects on the venous system are still largely unclear.
      OBJECTIVE: To evaluate the pressure of these medical elastic compression
      stockings on the skin and their edema protective effects. METHODS: On 18 legs the
      interface pressure of the stocking on the skin was measured with the aid of an
      interface pressure measuring instrument (Oxford Pressure Monitor). Five different
      kinds of medical elastic compression stockings were used. On 11 legs the edema
      protective effects of the different stockings was evaluated with the use of air
      plethysmography. RESULTS: All medical elastic compression stockings used in this
      study, especially the flat-knitted, showed a good pressure gradient from the B1
      level upwards. High pressures were measured at the dorsal foot and the pre-tibial
      zone. During cuff inflation a special edema protective effect was found in the
      round-knitted class II stockings. CONCLUSIONS: All class II and III medical
      elastic compression stockings used in this study have a sufficient pressure
      (especially class III) and pressure gradient for the treatment of patients with
      chronic venous insufficiency. Especially round-knitted stockings revealed high
      pressures on the danger areas such as the dorsal foot. All class II and III
      stockings provided an effective edema preventive effect; the round-knitted
      stockings have the best performance, due to their rubber components.

PMID- 9246171
TI  - Sapheno-femoral valves. Histopathological observations and diagnostic approach
      before surgery.
AB  - BACKGROUND: Since the literature indicated that in the early stages of primary
      venous disease valves are simply dilated, some authors performed external
      valvuloplasty of deep and superficial venous valves with encouraging results,
      although some failures were observed without being sufficiently explained.
      OBJECTIVE: To obtain further interpretations of the natural history of venous
      valve pathology, clarify methods for a correct diagnostic approach, and provide
      indications for the external valvuloplasty procedure. METHODS: Forty-two proximal
      valves of the long saphenous vein removed for varicose veins of the lower limbs
      were studied with optical microscopy. The relationship between histologic
      alterations and age of varicose disease was investigated. Five valvuloplasties
      were explanted for recurrent reflux and submitted to histopathological
      observation. Preoperative echographic findings and histologic observations were
      compared. Nineteen limbs were subjected to external valvuloplasty under
      angioscopic control; preoperative echographic findings and angioscopic
      observations were compared. RESULTS: The histologic alterations observed in
      venous valves were mainly hypotrophy of cusps, which seemed to be the main cause
      of failure after external valvuloplasty. The frequency of such hypotrophic
      alterations increases with the age of varicose disease but no statistically
      significant relationship was found. Preoperative echographic imaging of venous
      valves does not appear sufficiently predictive when compared with histologic and
      angioscopic examinations. CONCLUSION: Hypotrophic valve damage seems to be
      prevalent in patients with varicose veins of the lower limbs. Valve cusp
      hypotrophy may be present in early disease though some normal cusps can be found
      in advanced disease. When preoperative echographic visualization of cusps is
      doubtful, intraoperative angioscopy plays the main role in the diagnosis of
      venous valve disease before and during external valvuloplasty.

PMID- 9246172
TI  - Sclerotherapy of varicose veins of the lower limbs. Consensus paper. North
      American Society of Phlebology.

PMID- 9246173
TI  - Skin cancer and intraoperative radiation therapy: strange bedfellows.

PMID- 9246174
TI  - The chondrocutaneous helical rim advancement flap of Antia and Buch.

PMID- 9246175
TI  - Ambulatory phlebectomy.

PMID- 9246176
TI  - Peritumoral B cell infiltrate associated with chronic lymphocytic leukemia
      obscuring margin evaluation during Mohs micrographic surgery.

PMID- 9246177
TI  - Tikvah Alper: an indomitable spirit. 22 January 1909-2 February 1995.

PMID- 9246178
TI  - Radiation damage to cell membranes: insights from the oxygen effect.

PMID- 9246179
TI  - Parameters of linear-quadratic radiation dose-effect relationships: dependence on
      LET and mechanisms of reproductive cell death.
AB  - An analysis of mammalian cell radiation-dose survival curves, based on the linear
      quadratic formalism, is shown to yield insights in the various components of
      damage that contribute to cell reproductive death. RBE-LET relationships of
      single-track lethal damage, sublethal damage, potentially lethal damage and DNA
      double-strand breaks are compared. Single-track lethal damage is derived to be
      composed of two components: (1) damage that remains unrepaired in an interval
      between irradiation and assay for proliferative capacity, with a very strong
      dependence on LET, and (2) potentially lethal damage that is only weakly
      dependent on LET, similar to sublethal damage and DNA double-strand breaks. The
      results of this analysis lead to new interpretations of published experimental
      results and to suggestions for applications in radiotherapy.

PMID- 9246180
TI  - Cell-cycle sensitivity, recovery from radiation damage and a new paradigm for
      risk assessment.
AB  - Tikvah Alper's interest in science was broad, from scrapie to mammalian cells and
      cancer. Much of her own work focused on cell lethality, like that of many other
      radiobiologists, but this was natural because of the simplicity of the endpoint
      cell survival and its relevance to cancer therapy. Tikvah had broader interests,
      however, that included the effects of radiation on living systems in general like
      the induction of cancer and the cellular and molecular processes contributing to
      it. In this essay, some ideas are developed that lie in the mainstream of her
      interests. Starting with functional measures of the recovery or repair from
      radiation damage, a role for repair is illustrated in connection with mutagenesis
      and neoplastic transformation both discussed in the context of radiation-induced
      cancer. These topics are central to a model explaining the anomalous enhanced
      neoplastic transformation and cancer observed when low doses of a high-LET
      radiation are protracted in time. Under particular circumstances, the formalism
      of the model predicts application to protracted low-LET exposures as in the
      instance of repair-deficient target cells and sporadic breast cancer. The latter
      discussion leads to the proposal that the paradigm in current use for evaluating
      cancer risk should be broadened: from a simple dose-effect relation to one that
      includes cell kinetics (during protracted exposures), cell-cycle dependencies,
      and the influence of cellular repair or the lack thereof.

PMID- 9246181
TI  - What will molecular biology contribute to our understanding of radiation-induced
      cell killing and carcinogenesis?
AB  - The vast body of radiobiological data accumulated with mammalian systems in vitro
      and in vivo has had an enormous impact on radiotherapy. However, while
      quantitative, these data are essentially phenomenological, and it is only in the
      last decade or so that the techniques of molecular biology allow basic mechanisms
      to be understood. This will be illustrated by two examples, one involving cell
      killing and the other carcinogenesis. The identification and sequencing of repair
      and checkpoint control genes in the yeast S. pombe allow the mechanism of
      sensitivity/ resistance to radiation to be understood at the molecular level. The
      development of techniques to identify mutations in mismatch repair genes have
      made it possible to show that such mutations are associated with a wide range of
      human cancers and are a likely mechanism of radiation induced malignancies.
      Tikvah Alper would have been delighted to see the central role that micro
      organisms have played in these recent developments.

PMID- 9246182
TI  - DNA damage, repair and chromosomal damage.
AB  - An important question in radiobiology is the relationship between primary DNA
      damage and chromosomal aberrations. What determines the chromosomal aberration
      frequency, especially in radiosensitive cells? Much evidence points to the double
      strand break (dsb) as the critical lesion, however there is controversy over
      whether it is the initial induction, repair or residual dsb which determine of
      the level of expression of chromosome damage. The picture is further complicated
      by the fact that chromosome damage can be measured at several levels e.g. at
      metaphase, as micronuclei and as prematurely condensed chromosomes. Differential
      frequencies of chromosome damage are measured in different cell lines. Repair and
      residual dsb may play a role in metaphase aberrations when cells are exposed in
      G1, but in irradiated G2 cells the differential frequencies do not depend on
      repair of dsb or on the residual level of dsb since a difference in the cell
      lines is observed at short intervals after irradiation, and in radiosensitive
      cell lines where there is no deficiency in the repair of dsb, e.g. ataxia
      telangiectasia cells. Thus, at least in G2 cells, a mechanism involving
      'conversion' of dsb into chromatid breaks is proposed. There are a number of
      possible reasons for high conversion of dsb into chromatid breaks including
      altered chromatin structure, high chromosome condensation rates and covalent
      closure of chromosome ends.

PMID- 9246183
TI  - Predicting realistic RBE values for clinically relevant radiotherapy schedules.
AB  - To consider the therapeutic potential of radiation effect modifiers it is
      necessary to balance the modification of the injury in tumours with that in
      different types of normal tissue. It is especially important to ensure that the
      effects that have been demonstrated in preclinical experiments are both
      qualitatively and quantitatively relevant for the radiation doses that will be
      used in clinical schedules. Most radiobiology studies are initially performed
      with large single doses or a few large fractions, and from those results
      predictions have sometimes been made of the potential clinical benefit from a
      radiation modifier. In the clinic they will be used with many repeated small
      fractions of about 2 Gy over a period of several weeks. The effects will be
      quantitatively different in these two dose ranges for a variety of reasons. No
      modifiers of radiation effect are truly dose-modifying over the whole dose
      spectrum. They all have a differential effect on the type of damage inflicted at
      high and low dose levels, i.e. those described by the linear and quadratic terms
      in the LQ model. This means that every modifier has a dose or dose per fraction
      dependence on the magnitude of the sensitization or protection. The details of
      that dose dependence will vary with the alpha/beta ratio of the tissue under
      consideration. Furthermore all tissues and tumours contain a mixture of cells,
      with different proliferative, redox and other characteristics that influence
      their sensitivity to radiation and their susceptibility to the radiomodifier. The
      influence of different subsets of cells changes as a fractionated treatment
      progresses and the sensitive cells are eradicated, leaving more resistant
      survivors. The overall response to a fractionated schedule then depends
      critically on whether there is re-assortment of cells from the resistant phase
      into more sensitive or modifiable phases before the next fraction in the series.
      In addition, the magnitude of dose modification depends totally on the standard
      curve against which the comparison is made. The reference standard is different
      in preclinical laboratory studies and in conventional clinical experience. Those
      differences must be considered when moving from the laboratory to the clinic and
      back again. The effect of these different factors is considered using the linear
      quadratic model to dissect the components. Examples are provided to demonstrate
      the clinical relevance.

PMID- 9246184
TI  - Apoptosis: an indicator of radiosensitivity in vitro?
AB  - The mechanisms by which ionizing radiation kills cells was a topic of great
      interest to Dr Alper, and one suspects that she would have delighted in
      'clarifying' the role of apoptosis. Indeed, clarification seems necessary in view
      of the abundance of often conflicting data currently emerging. However, given
      some simplifying assumptions, important patterns can be discerned. The following
      comments are thus framed in the context of haematopoietic cell lines, which
      generally undergo rapid apoptosis (within hours) following irradiation, in
      contrast to cells of non-haematopoietic origin, which are more likely to be
      characterized by delayed apoptosis (within days). Tolerance for DNA damage
      appears to be reduced in cells capable of rapid apoptosis, and those cells are
      sensitized to ionizing radiation when the apoptotic response mechanisms are fully
      functional. This rapid apoptotic response shows minor sensitivity to cell cycle
      position or radiation dose rate. Different considerations apply, however, for the
      delayed response. Delayed apoptosis appears to be triggered by chromosome damage,
      and evidence implicating delayed apoptosis as a modifier of cellular
      radiosensitivity is much less convincing at present.

PMID- 9246185
TI  - Apoptosis and mitotic cell death: their relative contributions to normal-tissue
      and tumour radiation response.
AB  - The target-cell theory of tissue responses is reviewed with reference to the
      radiosensitivity of proposed target cells in bone marrow, intestine, epidermis,
      and spermatogenesis. The difficulties in precisely identifying target cells using
      histological/cell marker criteria, and hence determining the role of their mode
      of death in tissue responses, are being circumvented to some extent by the recent
      use of mice deficient in gene products required for radiation-induced apoptosis.
      In this case cell death results from 'mitotic cell death' and e.g. in the case of
      p53, any remaining p53-independent apoptosis. In the p53 null mouse, cell
      survival levels are increased in bone marrow and intestine but decreased in the
      testis. Different interpretations, based on the lack of p53-dependent apoptosis
      or the lack of a permanently induced G1-arrest in the case of marrow fibroblasts,
      can be applied to the results for different cell types. Hence both apoptosis and
      mitotic cell death can variously be involved as contributing to target-cell
      sensitivity and hence to early reactions in these tissues after irradiation. It
      is still unclear whether, or how, the mode of cell death (apoptotic versus
      mitotic) determines the radiosensitivity and response of tumours. In experimental
      tumours, the levels of radiation-induced apoptosis have been shown to correlate
      both with the in vivo response to radiation and the degree of spontaneous
      apoptosis in the tumours. Measurements of spontaneous apoptosis in human tumours,
      however, have yielded conflicting data with high apoptotic levels significantly
      correlating with both good and poor prognosis in different studies. There is one
      report of a lack of relationship between intrinsic radiosensitivity and
      spontaneous apoptosis in cervical cancers. In contrast several studies have
      reported correlations between apoptosis levels and the degree of tumour cell
      proliferation. Tumour hypoxia has also been shown to increase apoptosis. These
      data suggest that tumour apoptosis may be a reflection of intrinsic
      radiosensitivity, tumour cell proliferation and tumour hypoxia. Its relative
      importance will probably be tumour type, size and stage related.

PMID- 9246186
TI  - Low dose hyper-radiosensitivity and increased radioresistance in mammalian cells.
AB  - This manuscript reviews the low-dose survival work using the DMIPS cell analyser
      that has been carried out at the Gray Laboratory in the U.K. and the British
      Columbia Cancer Research Centre in Canada. It describes low dose hyper
      radiosensitivity (HRS) detected after single doses of X-rays less than
      approximately 0.3 Gy and the subsequent increased radioresistant response (IRR)
      seen as the dose increases up to 1 Gy. Work is summarized from studies in V79
      cells, normal human and human tumour cell lines and mutant cell lines deficient
      in DNA repair. The data are considered in light of the hypothesis that hyper
      radiosensitivity and increased radioresistance reflect the existence of an
      inducible protective mechanism, possibly triggered by DNA damage.

PMID- 9246187
TI  - Substructure in the cell survival response at low radiation dose: effect of
      different subpopulations.
AB  - In order to obtain more accurate measurements of cell survival after low doses of
      radiation, we have used the cell sorter assay, in which a cell sorter is used to
      accurately count out the number of cells plated for colony formation. This
      method, combined with data averaging, permits measurements of survival with
      superior precision, which have revealed that there is substructure in the
      radiation response of asynchronously dividing Chinese hamster cells. The
      substructure, observed at doses of a few Gy, has features of a 2-component
      response, consistent with the presence of subpopulations of cells of different
      cell-cycle-related radiosensitivity. The absence of any substructure in the
      radiation response of homogeneous (tightly synchronized) cell populations lends
      strong support to this subpopulation explanation of the substructure. This assay
      has also been used on a variety of human tumour cell lines, most of which
      exhibited substructure similar to that of Chinese hamster cells. This paper
      outlines the application of the cell sorter assay to three different problems:
      (i) radiosensitizer mechanisms-etanidazole and RB 6145 are shown to enhance
      primarily the beta term and alpha term, respectively, of tumour cell kill,
      indicating that sensitizer efficacy may be tumour-specific and predictable from
      tumour response parameters; (ii) accurate measurement of Relative Biological
      Effectiveness (RBE) in a modulated clinical proton beam shows that the RBE is
      both dose- and depth-dependent; and (iii) measurements at lower doses clearly
      demonstrate a second order of substructure, termed the hypersensitive response,
      at doses < 1 Gy.

PMID- 9246188
TI  - Lethal mutations and genomic instability.
AB  - The delayed expression of cell death in progeny of irradiated survivors was
      christened 'lethal mutations' by Tikvah Alper in 1984. The effect occurs when
      clones, or populations of cells grown up from irradiated progenitor cells, are
      replated and reassessed for cloning efficiency or population doubling time. The
      effect has been shown to be associated with the low dose shoulder region of the
      survival curve and is due to events occurring in the first two hours post
      irradiation, i.e. the 'fast repair' period. In this review the lethal mutation
      data accumulated over the past ten years is discussed in relation to our modern
      understanding of cellular and molecular events in radiation carcinogenesis and
      genomic instability research. It is suggested that lethal mutations are
      associated with a general epigenetic or field effect occurring in all irradiated
      cells, which makes them more prone to mutations, some of which are lethal. The
      implications of this for our current approach to risk estimates and therapeutic
      dose calculation, need to be addressed.

PMID- 9246189
TI  - Ongoing Y-chromosome instability defines sub-clonal variants in radiation-induced
      leukaemias in the mouse.
AB  - Forty primary leukaemias that arose in vivo as a consequence of 3 Gy X
      irradiation of inbred mouse strains were analysed for Y-chromosome aberrations by
      conventional cytogenetics and fluorescent in situ hybridization (FISH). Compared
      with control mice which were X-irradiated but which exhibited no overt signs of
      leukaemia, the loss and gain of Y-chromosomes in leukaemic spleen cells defined
      subclonal variants in the radiation-induced haemopoietic malignancies that arose
      in CBA/H, DBA/2 and (C57BL/6 x DBA/2)F1 mice. This Y-chromosome instability was
      significantly higher than that observed in spleen cells of age-matched (or older)
      irradiated control mice that had not developed overt leukaemia. The detection of
      Y-chromosome aberrations is considered in the context of the high numbers of
      potential gene regulatory sequences in the murine Y-chromosome and the potential
      for the insertional activation of cellular genes during multi-stage radiation
      leukaemogenesis.

PMID- 9246190
TI  - Relationship between radiation response and p53 status in human bladder cancer
      cells.
AB  - Mutations in the p53 tumour suppressor gene are found at high frequency in
      bladder cancer. There is strong evidence that p53 plays an important role in
      controlling the cell cycle after DNA damage by ionizing radiation. However, the
      effect of loss of p53 function on radiosensitivity is not yet clear. Radiotherapy
      combined with chemotherapy is the most common treatment for patients with
      invasive bladder cancer. Recently three bladder cancer cell lines have been
      established and this paper investigates the p53 status and clonogenic survival of
      these cell lines following irradiation. It was found that one line expresses wt
      p53 (UCRU-BL-13) and two lines contain a codon 72 polymorphism (UCRU-BL-17 and
      UCRU-BL-28). UCRU-BL-17 cells also contain a point mutation affecting codon 280.
      The level of p53 expression in the cell lines is clearly different, with UCRU-BL
      17 expressing a higher level of p53 compared with UCRU-BL-13; UCRU-BL-28
      expressed intermediate levels. The clonogenic survival of these cell lines has
      been determined. It was found that the line expressing a p53 mutation was more
      sensitive than those with wild type p53, providing support for a model in which
      loss of p53 function is associated with increased radiosensitivity, possibly due
      to reduced p53-dependent DNA repair.

PMID- 9246191
TI  - Induction of multiple PCR-SSCPE mobility shifts in p53 exons in cultures of
      normal human urothelium exposed to low-dose gamma-radiation.
AB  - We have previously shown that primary explant cultures of human urothelium
      exposed to low doses of gamma-radiation subsequently accumulate a high level of
      stable p53 but it was not clear from those studies whether this protein
      stabilization occurred through an event in another gene involved in p53 protein
      control or possibly an epigenetic event. In these experiments, primary urothelial
      cultures from five different patients were exposed to either 0.5 or 5 Gy gamma
      radiation from a 60 Cobalt source and allowed to grow for 7-10 division cycles to
      allow development of any radiation-induced, non-lethal changes in the cells. C
      myc, Bcl-2 and stable p53 proteins were found to be elevated in cultures
      following both radiation doses. PCR-SSCPE analysis of the p53 gene was performed
      on cultures in order to determine whether genetic mutations could be the
      underlying basis for persistent increased stable p53 expression. Following 0.5 Gy
      exposure, the cultures also developed multiple distinct 'foci' of rapidly
      dividing cells which strongly overexpressed p53. These grew on a background of
      morphologically normal cells. When such foci were selectively analysed for their
      p53 mutation status by PCR-SSCPE, there was evidence that they contained cells
      which had developed changes to the p53 gene post-irradiation. These changes
      appeared to occur more frequently in focal cells than in cells of normal
      morphological appearance in the same culture. These results may have mechanistic
      importance given the controversy regarding low-dose radiation effects and p53
      related genomic instability.

PMID- 9246192
TI  - Induction of interleukin 6 by ionizing radiation in a human epithelial cell line:
      control by corticosteroids.
AB  - The cutaneous radiation syndrome after therapeutic or accidental exposure of
      human skin to ionizing radiation (IR) is accompanied by inflammatory processes
      which are controlled partly by proinflammatory cytokines. Besides tumour necrosis
      factor (TNF)-alpha and interleukin (IL)1, the pluripotent cytokine IL-6 belongs
      to the key mediators of inflammation. So far, there are no reports about the
      regulation of IL-6 by IR in epidermal cells. As an in vitro model to study the
      effects of IR on IL-6 gene expression, we treated the human epithelial HeLa cell
      line with different single X-ray doses between 1 and 20 Gy. Twenty-four hours
      after irradiation the IL-6 secretion was dose-dependently enhanced as measured by
      ELISA. At the transcriptional level, a slight increase of IL-6 transcripts was
      already detectable 1 h after irradiation, with maximum levels at 2 h, and a
      decline to baseline levels between 8 and 24 h. Addition of the transcriptional
      inhibitor actinomycin D inhibited the inducibility of IL-6 mRNA by TPA and IR. As
      the IL-6 promoter contains multiple binding sites for activated glucocorticoid
      receptors within the 5' regulatory region, the potential modulation of IL-6
      expression by the corticosteroids hydrocortisone, dexamethasone and mometasone
      furoate was included in our study to modify the radiation-induced stress
      response. All corticosteroids applied could efficiently downregulate TPA- or
      radiation-induced IL-6 expression on both gene expression and protein levels.
      Mometasone furoate, followed by dexamethasone, was found to be most effective at
      low concentrations (1 nM), whereas hydrocortisone had to be applied at about 100
      fold higher concentrations to achieve comparable inhibition. This experimental
      model is aimed at understanding the molecular circuits following IR, and thus to
      provide a basis for the treatment of radiation effects in skin.

PMID- 9246194
TI  - Photo-induced inactivation of dihydroorotate dehydrogenase in dilute aqueous
      solution.
AB  - The inactivation of dihydroorotate dehydrogenase was studied by irradiating at
      selective wavelengths, namely 280 nm and 450 nm, using a steady-state Xenon lamp
      as a light source. The activity of the enzyme decreased exponentially as a
      function of the absorbed dose under both aerated and deaerated conditions. The
      inactivation in deaerated conditions is higher than that in aerated conditions
      when enzyme solutions were irradiated at 450 nm, whereas inactivation under
      aerated conditions was slightly higher compared with that in Ar-saturated
      condition when irradiated at 280 nm. No change in fluorescence spectral shape was
      observed, however, intensity of emission maximum was found to decrease, except in
      one case. The fluorescence intensity of flavin was found to increase with
      absorbed dose when the enzyme was irradiated at 280 nm in aerated solution.
      Changes in the kinetic parameters (Michaelis-Menten constant, Km, and maximal
      velocity, Vmax) due to irradiation at 280 nm suggests that the substrate-binding
      site is modified in deaerated conditions but not in aerated conditions.

PMID- 9246193
TI  - Delayed molecular responses to brain irradiation.
AB  - The chance of life-threatening complications occurring late after brain
      irradiation limits the efficacy of this form of cancer therapy. The molecular and
      cellular events that trigger radiation-induced brain damage are still unknown,
      but since they have the potential to serve as valuable targets for therapeutic
      intervention they are worth delineating. In this murine study, the effect of
      irradiation on the expression of molecules which are known to contribute to brain
      damage in other model systems was examined. Expression of genes encoding
      cytokines (TNF-alpha/beta, IL-1 alpha/beta, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN
      gamma), cytokine receptors (TNF-Rp55 and p75, IL-1R- p60 and p80, IFN-gamma R,
      and IL-6R), the cell adhesion molecule (ICAM-1), inducible nitric oxide
      synthetase (iNOS), anti-chymotrypsin (EB22/5.3), and the gliotic marker (GFAP)
      was evaluated over a 6-month period using a sensitive RNase protection assay
      (RPA). We had previously demonstrated that within 24 h of brain irradiation there
      is an acute transitory molecular response involving TNF-alpha, IL-1, ICAM-1,
      EB22/5.3 and GFAP. This study shows re-elevation of TNF-alpha, EB22/5.3 and GFAP
      mRNA levels at 2-3 months, but only TNF-alpha mRNA was overexpressed at 6 months.
      These time points are when neurological abnormalities are seen after higher
      doses. The data suggest that TNF-alpha may be involved in late brain responses to
      irradiation and could contribute to clinical symptoms.

PMID- 9246195
TI  - Lysozyme fragmentation induced by gamma-radiolysis.
AB  - Irradiation of lysozyme in frozen states in the absence of oxygen induces
      specific fragmentation at defined sites along the backbone chain. This paper
      localizes radio-fragmentation sites by two methods. First, N-terminal sequencing
      of radiolysis fragments after separation by SDS-polyacrylamide gel
      electrophoresis and estimation of their molecular masses. Secondly, after
      purification of radiolysis fragments by reverse phase-HPLC and determination of
      their molecular mass by electro-spray-ionization mass-spectrometric analysis,
      combined to N-terminal sequencing and total amino acid analysis. Evidence for the
      breakage of the peptide bond itself (CO-NH) is given, with radio-fragmentation
      sites mostly found at the surface of irradiated lysozyme in solvent exposed loops
      and turns.

PMID- 9246196
TI  - Effect of a maternal injection of 239Pu on the number of CFU-S in the foetal
      liver of the C3H and BDF1 mouse.
AB  - We investigated the effect of 239Pu administered on day 4 of gestation on the
      number of CFU-S (spleen-colony forming units) in the foetal liver on day 17 of
      gestation in the C3H and BDF1 mouse. CFU-S numbers in the foetal liver were
      decreased significantly by 239Pu at doses > 30 kBq/kg body weight in the BDF1
      mouse, but were not changed by up to 900 kBq/kg in the C3H strain. Quantitative
      autoradiography on days 6, 8 and 10 of gestation and liquid scintillation
      counting on days 13 and 17 of gestation revealed no significant differences in
      the distribution and concentration of 239Pu between the foetoplacental units of
      these two strains. These findings suggest a strain difference in the effect of
      239Pu alpha-irradiation on the development of the foetal haematopoietic systems
      in the mouse.

PMID- 9246197
TI  - Cytotoxicity of alpha-particle-emitting 5-[211At]astato-2'-deoxyuridine in human
      cancer cells.
AB  - This study was performed to determine the cytotoxicity of alpha-particle-emitting
      5-[211At]astato-2-deoxyuridine (i.e. [211At]AUdR) for monolayers of D-247 MG
      human glioma cells and SK-MEL-28 human melanoma cells. Cells in exponential
      growth were exposed to varying activity concentrations of [211At]AUdR and for
      comparison [211At]astatide and the Auger electron-emitting analogue, 5-[125I]iodo
      2'-deoxyuridine (i.e. [125I]IUdR). Cell uptake, DNA binding and clonogenic
      survival as a function of activity concentration in the medium were determined
      following 2 and 20-h incubations. None of the survival curves had detectable
      shoulders, an observation consistent with high-LET effects. The A37 (initial
      activity concentration yielding 37% cell survival) were significantly lower for
      both cell lines following 20-h exposure of [211At]AUdR than [211At]astatide.
      After correcting for effects from non-cell-associated activity in the medium, the
      specific cytotoxicity of cell-associated and DNA-bound [211At]AUdR was estimated.
      In the 20-h incubation experiments, the A37 for DNA-associated [211At]AUdR
      corresponded to about one 211At atom bound per cell for both cell lines. Unlike
      [211At]AUdR, there was a biphasic survival response to [125I]IUdR, consistent
      with the lower fractional uptake of [125I]IUdR at higher activity concentrations.
      These studies suggest that [211At]AUdR warrants further evaluation as an
      endoradiotherapeutic agent for the treatment of rapidly proliferating cancers.

PMID- 9246198
TI  - Radiosensitivity and double-strand break rejoining in tumorigenic and non
      tumorigenic human epithelial cell lines.
AB  - Radiosensitivity and repair of DNA damage induced by ionizing radiation and
      restriction enzymes were investigated in three human epithelial cell lines: two
      tumorigenic squamous carcinoma cell lines (SCC-4 and SCC-25), and a non
      tumorigenic epidermal keratinocyte cell line (RHEK-1). Sensitivity to ionizing
      radiation was determined using a clonogenic cell survival assay, which showed SCC
      4 to be more radiosensitive than SCC-25 and RHEK-1, which in turn displayed about
      equal sensitivity. Using DNA precipitation under alkaline conditions for the
      analysis of induction and repair of DNA single-strand breaks (ssb), an increased
      level of ssb induction was found for SCC-4 while the efficiency of ssb repair was
      about equal in all three cell lines. Using pulsed-field gel electrophoresis
      (PFGE) for the measurement of induction and repair of DNA double-strand breaks
      (dsb), no consistent differences were detected between the three cell lines. A
      plasmid reconstitution assay was used to determine the capacity to rejoin
      restriction enzyme-induced dsb in whole-cell extracts prepared from the three
      cell lines. In these experiments, dsb rejoining was shown to be significantly
      reduced in the most radiosensitive SCC-4 cell line while it was about equal in
      RHEK-1 and SCC-25. The results indicate that plasmid reconstitution in cell-free
      extracts is a sufficiently sensitive assay to detect differences in repair
      capacity among tumour cell lines of different radiosensitivity which remain
      undetectable by DNA precipitation and PFGE.

PMID- 9246199
TI  - Modification of potentially lethal damage in irradiated Chinese hamster V79 cells
      after incorporation of halogenated pyrimidines.
AB  - Radiosensitization of exponentially growing and plateau phase Chinese hamster V79
      cells by incorporation of halogenated pyrimidines (HP) was investigated for
      different culture conditions that influenced repair. For this purpose cells were
      grown for 72 h with 0, 1, 2 and 4 microM of chloro-(CldUrd), bromo- (BrdUrd) or
      iodo-deoxyuridine (IdUrd) and were subsequently irradiated with gamma-rays from a
      197Cs source, either in exponential growth or in plateau-phase. Cell survival
      after irradiation was determined by clonogenic assay. In exponentially growing
      cultures thymidine-replacement in the DNA of the cells after incubation with 4
      microM of CldUrd, BrdUrd and IdUrd was 22.3, 32.7 and 12.7%, respectively. In
      plateau-phase cultures the percentage thymidine replacement in the DNA of the
      cells after incubation during growth with 4 microM CldUrd, BrdUrd and IdUrd was
      27.5, 33.8 and 10.7%, respectively. Linear-quadratic analyses of the radiation
      survival curves were performed. In exponentially growing cells a marked increase
      by a factor 2-3 of the value of alpha was obtained. The beta term significantly
      increased only in cells which were grown in the presence of BrdUrd and which were
      trypsinized and replated immediately after irradiation. In plateau-phase cells
      which were trypsinized and plated immediately after irradiation both alpha and
      beta increased up to a factor 2-3 with increasing incorporation of halogenated
      pyrimidines. In plateau phase cells which were allowed to repair potentially
      lethal damage (PLD) for 6 h and subsequently trypsinized and plated, alpha
      increased by a factor 3-4. In these latter conditions changes in beta were
      smaller. In exponentially growing cells in which repair was allowed after
      irradiation by plating prior to the treatment, the alpha values decreased for all
      the HP drugs tested as compared to the alpha of cells plated immediately after
      irradiation. In contrast, delay of plating for plateau phase cells yielded
      increased alpha values not only when compared with the alpha of plateau phase
      cells plated immediately after treatment but also when compared with the alpha
      value of radiosensitized exponentially growing cells. The increase of alpha might
      be interpreted as an enhancement in the expression of PLD. The larger
      contribution of fixation of PLD might be due to initial DNA damage and/or to
      inhibition of PLD repair resulting from incorporation of HP. The increase of beta
      might be attributed to enhanced interaction or to fixation of sublethal damage
      (SLD). In view of clinical applications of HP it is of interest that
      sensitization is not abolished in plateau-phase cells.

PMID- 9246200
TI  - Comparative effects of UV A and UV B on clonogenic survival and delayed cell
      death in skin cell lines from humans and fish.
AB  - The effects of UV radiation on humans and animals are receiving increasing
      attention and much interest has recently been focused on the environmental
      effects of UV A and UV B. This study compares the in vitro effects of UV A and UV
      B on the clonogenic survival of two human skin keratinocyte cell lines, HaCaT
      which are immortal but not tumorigenic and HPV-G transfected keratinocytes which
      form non malignant tumours in nude mice. The effects were also studied on an EPC
      fish cell line. The aim of the work was to establish if similar initial and
      delayed survival responses occurred in both species. The cells were exposed to
      ultraviolet lamps emitting maximally at 365 nm (UV A) and 302 nm (UV B).
      Clonogenic survival was determined at appropriate times post exposure. Results
      for the initial survival curves show that the HaCaT and HPV-G cells did not show
      any appreciable difference in their response to UV A but the EPC cells were more
      sensitive at doses < 3000 Jm-2. The EPC cells were more sensitive to UV B at
      doses < 200 Jm-2 in comparison to the human HaCaT and HPV-G cells with the HPV-G
      cells showing the most sensitivity to UV B at doses > 200 Jm-2. The possible
      contribution of lethal mutations (delayed cell death) to the UV radiation
      response in the HaCaT and EPC cell lines was examined. The results showed that
      lethal mutations were expressed in the HaCaT cells following exposure to UV A and
      UV B but no lethal mutations were expressed in the EPC cells.

PMID- 9246201
TI  - Effects of heavy ions on the germination and survival of Arabidopsis thaliana.
AB  - Inhibition of germination and reduction in survival of Arabidopsis thaliana were
      investigated to study the effects of heavy ions on a multicellular system. Dry
      seeds of Col and Ler ecotypes were exposed to He, C, Ar and Ne ions with linear
      energy transfer (LET) in the range of 17-549 keV/micron and to electrons (LET =
      0.2 keV/micron). The relative biological effectiveness (RBE) for the survival of
      both ecotypes showed the same pattern of variation with a maximum RBE of 11-12 at
      252 keV/micron. For germination, RBE increased with increasing LET in Ler but not
      in Col, showing different sensitivities between the plant ecotypes. Inactivation
      cross sections of survival increased linearly in the range of 0.2-17 keV/micron
      and proceeded more steeply in the range of 113-252 keV/micron. At higher LET,
      cross sections appeared to reach a plateau at a little less than the size of the
      cell nucleus. When the value for survival was plotted against LET, it decreased
      steeply in the range about 113-252 keV/micron, indicating that heavy ions may
      have similar effects on both the shoulder and slope of the survival curve.

PMID- 9246202
TI  - Priming to mycobacterial antigen in vivo using antigen-pulsed antigen presenting
      cells generated in vitro is influenced by the dose and presence of IL-4 in APC
      cultures.
AB  - Antigen presenting cells (APC) similar to immature dendritic cells can be
      generated in vitro from bone marrow precursors. The authors have compared the
      yield, the phenotype and the function of murine bone marrow cells cultured for 7
      or 11 days in either granulocyte macrophage colony stimulating factor alone (GM
      BMAPC) or in combination with interleukin-4 (GM/IL-4 BMAPC). The results showed
      that GM/IL-4 BMAPC expressed the highest levels of MHC Class 2 molecules, CD86/B7
      2 and CD80/B7-1 co-stimulatory molecules and the lowest levels of F4/80
      macrophage marker. However, when these APC were pulsed with BCG culture filtrate
      antigen or PPD they were not correspondingly more effective at stimulating
      activated T lymphocytes in vitro or priming naive T lymphocytes in vivo. Also, in
      contrast to GM BMAPC, high backgrounds recorded following injections of GM/IL-4
      BMAPC without antigen were not consistently reduced by lowering the dose and
      irradiating the cells prior to administration. The authors conclude that the
      degree of maturity of BMAPC varies with culture conditions and that this may be
      an important consideration where BMAPC are to be used in vivo in
      immunotherapeutic regimens.

PMID- 9246203
TI  - Early expansion of secondary B cells after primary immunization with antigen
      complexed with IgE.
AB  - IgE antibodies have potent immunoregulatory effects in vivo, and mice immunized
      with IgE-antigen (IgE/ Ag) complexes exhibit a several hundred-fold higher
      humoral Ag-specific response than mice immunized with non-complexed Ag. In vitro
      studies indicate that this is a result of efficient endocytosis of the IgE/Ag
      complexes via the low-affinity receptor for IgE (CD23) on B cells, leading to
      efficient antigen presentation to T cells. Previous studies of IgE-induced Ab
      responses in vivo have only measured serum responses. The authors have now
      studied the up-regulated response as the number of IgG-, IgA-, IgE- and IgM
      secreting single B cells in spleen, lymph nodes and bone marrow of mice immunized
      with IgE-anti-TNF+BSA-TNP (2,4,6-trinitrophenylated bovine serum albumin). IgE
      and Ag induced a greater than 500-fold increase of specific IgG-secreting spleen
      cells with the peak of the response 6 days after primary immunization. The
      response of other Ab isotypes and the response in other lymphoid organs was
      marginal. The rapid increase in the number of IgG-secreting cells in the spleen
      suggests that IgE/Ag complexes induce a secondary type of antibody response
      without requirement for conventional priming.

PMID- 9246204
TI  - Cross-reactive immune responses against Mycobacterium bovis BCG in mice infected
      with non-tuberculous mycobacteria belonging to the MAIS-Group.
AB  - Two bacillus Calmette-Guerin (BCG)-susceptible mouse strains, BALB/c and C57BL/6,
      were infected intravenously with Mycobacterium intracellulare, M. avium or M.
      scrofulaceum and monitored during 3 months for mycobacterial replication and
      antibody and Th1-type cytokine production in response to cytoplasmic and secreted
      antigens from M. bovis BCG. Whereas initial colony-forming unit (CFU) counts of
      M. intracellulare and M. avium were higher in lungs than in spleen, the opposite
      was observed for M. scrofulaceum. Mycobacterium intracellulare was the most
      virulent species and its replication could not be controlled in either mouse
      strain. It also induced the strongest antibody response. Mycobacterium avium was
      eliminated in both mouse strains and M. scrofulaceum finally was eliminated in
      C57BL/6 but multiplied in spleen from BALB/c mice. Significant sustained
      interleukin-2 and interferon-gamma production towards BCG antigens was only found
      in M. scrofulaceum infection. As in BCG-vaccination, M. scrofulaceum-infected
      C57BL/6 mice demonstrated a higher response towards whole BCG culture filtrate,
      BCG extract and purified antigen 85 complex (Ag85) from BCG than did BALB/c mice.
      The data suggest that the presence of M. scrofulaceum in the environment may
      possibly interfere in genetically predisposed subjects with BCG vaccine and its
      protective efficacy against M. tuberculosis.

PMID- 9246205
TI  - Carbohydrate recognition on MUC1-expressing targets enhances cytotoxicity of a T
      cell subpopulation.
AB  - The influence of the epithelial mucin MUC1 on T cell-mediated lysis was analysed
      using lymph node lymphocytes (LNL) from patients with colorectal carcinoma. LNL
      were stimulated with allogeneic, MUC1-transfected B cells and the bulk cultures
      were cloned. Alloreactive cytotoxic T cell clones were obtained which
      preferentially lysed MUC1-expressing targets. The majority was CD4+ and MHC-class
      II-restricted, and a minor group was CD8+ and MHC-class I-restricted. All the
      clones expressed CD3 and TCR alpha beta, and were CD56-. The capacity to
      preferentially kill MUC1-expressing targets was stable in several clones for up
      to 6 months in culture. The enhancing effect of MUC1 on the lysis was
      investigated in more detail. It was only seen after inhibition of O-linked
      glycosylation in the targets. Furthermore, this effect was completely abrogated
      by the monoclonal antibody 3C9, directed against the Thomsen-Friedenreich antigen
      (T-antigen, Gal beta 1-3GalNAc bound alpha 1-3 to Ser/Thr) as well as by the
      soluble disaccharide Gal beta 1-3GalNAc, but not by other similar disaccharides.
      The authors conclude that in their system the preferential killing of MUC1
      expressing targets is due to the recognition of an internal carbohydrate epitope
      accessible on under-glycosylated MUC1, possibly T-antigen, by an auxiliary
      receptor molecule on T cells.

PMID- 9246206
TI  - Experimental infection of Balb/c mice with Leishmania panamensis and Leishmania
      mexicana: induction of early IFN-gamma but not IL-4 is associated with the
      development of cutaneous lesions.
AB  - Resistance to the Leishmaniae is associated with interferon (IFN)-gamma mediated
      activation of macrophages. In this study, Balb/c mice were infected with three
      Leishmania strains that cause progressively growing cutaneous lesions without
      obvious dissemination: L. mexicana mexicana giving rise to rapidly growing
      lesions, and L. (Viannia) panamensis and L. mexicana-like, which both cause
      slowly developing lesions. The rate of lesion growth was compared to induction of
      early local and systemic IFN-gamma responses. All the three parasite strains
      induced increased levels of IFN-gamma transcripts 24 h after infection. Infection
      with the more aggressive strain resulted in a notably lower IFN-gamma response
      when compared to infection with the two low pathogenic strains. Interleukin-4 (IL
      4) mRNA appeared 7 days after infection with L. (Viannia) panamensis and L.
      mexicana-like but not with L. mexicana mexicana. Thus, virulence of these
      Leishmania strains could not be associated with induction of IL-4 during the
      first week after infection. In addition, none of the Leishmania strains induced
      detectable mRNA for IL-12 or inducible nitric oxide synthase (iNOS). These data
      present a picture somewhat different from that which has been described in L.
      major experimental infection.

PMID- 9246207
TI  - Interaction of 2C T cells with a hybrid Ld molecule bearing an alpha 3 domain
      derived from the class IB molecule, Qa-2.
AB  - The CD8 co-receptor interacts with nonpolymorphic residues on class I molecules.
      LQ3, a laboratory engineered Ld molecule bearing an alpha 3 domain derived from
      Q7 (Qa-2), interacts poorly with anti-Ld CD8-dependent T cells. 2C TCR transgenic
      mice bear a receptor specific for the p2Ca peptide bound to Ld. The authors show
      that although this peptide interacts with LQ3, LQ3 APC fail to activate splenic
      2C CD8 T cells in vitro in the absence of IL-2, while control Ld APC do. The
      authors have used this receptor ligand pair to examine negative selection within
      the thymus of (B6 x C3H.Ld)F1 versus (B6 x C3H.LQ3)F1 radiation chimeras
      repopulated with 2C bone marrow cells. While positive selection occurs normally
      in (B6 x C3H)F1 chimeras, animals expressing either Ld or LQ3 fail to generate 2C
      CD8+ cells. Thus, either CD8 is not required for negative selection of this TCR
      or a weak interaction of CD8 with LQ3 is sufficient. TSA-1, a developmentally
      regulated marker, was used to follow the process of negative selection. The
      results show that deletion of 2C T cells does not occur until thymocytes reach
      the double positive (DP) stage. Furthermore, the authors noted a small population
      of DP TSA-1hi cells remains, while DP TSA-1int and TSA-1lo cells are absent.
      These data support the notion that thymocytes either reach a particular stage of
      development or locate in an appropriate intrathymic compartment before they
      undergo negative selection.

PMID- 9246208
TI  - Efficient in vitro cleavage of mouse acute phase serum amyloid A mRNA mediated by
      a synthetic hammerhead ribozyme.
AB  - The authors designed a hammerhead ribozyme, mRibSAA2, to cleave the mRNA for
      mouse acute phase serum amyloid A 2 (A-SAA2), a major acute phase protein that is
      massively induced during inflammation and that is deposited as fibrils during
      secondary amyloidosis. Using computer based secondary structure analysis, a GUC
      triplet (nucleotides 408-410) on a predicted stem loop in A-SAA2 mRNA was chosen
      as the target site for mRibSAA2. The ribozyme was tested in vitro and gave
      efficient and specific magnesium-dependent cleavage of mouse A-SAA2 mRNA into the
      expected fragments of 197 and 425 bases. The authors also demonstrated that the
      ribozyme retains cleavage activity over several hours. The use of the mRibSAA2
      ribozyme as a research tool and possible therapeutic agent in mouse models of
      amyloidosis is discussed.

PMID- 9246209
TI  - Colostral mononuclear phagocytes are able to kill enteropathogenic Escherichia
      coli opsonized with colostral IgA.
AB  - Enteropathogenic Escherichia coli (EPEC) is the main aetiological agent of acute
      diarrhoea among low socioeconomic level infants in developing countries. Breast
      feeding provides infant protection against acute gastrointestinal and respiratory
      infections; however, little is known about the protective role of colostral
      phagocytes in the gut of newborn infants. In the present investigation we studied
      the ability of human colostral MN phagocytes to kill EPEC as well as the
      interactions between these cells and colostral and serum opsonins. The authors
      observed that the microbicidal activity of colostrum MN phagocytes was dependent
      on previous EPEC opsonization with colostral supernatant or blood serum. A
      defatted colostrum supernatant pool presented opsonic activity for EPEC killing
      at levels equivalent to those of normal serum. IgA-depleted colostrum supernatant
      showed significantly lower opsonic activity, whereas purified IgA from the same
      colostrum pool was a potent opsonin which induced EPEC killing at levels
      equivalent to those of untreated colostrum. Colostral MN phagocytes are able to
      release superoxide anion when incubated with both EPEC opsonized with untreated
      colostrum and purified IgA. Purified IgA was also able to restore opsonic
      activity of IgA-depleted colostrum. A colostrum pool without C3 and IgG induced
      EPEC killing by colostral MN phagocytes at rates equivalent to those of untreated
      colostrum supernatant. Addition of an IgM MoAb (My43) anti-human Fc alpha
      receptor resulted in a significant inhibition of EPEC killing when bacteria were
      opsonized with purified IgA, suggesting an interaction between IgA and Fc alpha
      R. With respect to serum opsonins, we observed that IgG plus complement component
      C3 were necessary to induce EPEC killing by the colostrum MN phagocytes.
      Colostral phagocyte killing of enteropathogenic bacteria may represent an
      additional mechanism of breast-feeding protein against intestinal infections
      during the first week of life.

PMID- 9246211
TI  - Antibody reactivity against thyroid peroxidase and myeloperoxidase in autoimmune
      thyroiditis and systemic vasculitis.
AB  - Potential cross-reactivity between thyroid peroxidase (TPO) and myeloperoxidase
      (MPO) molecules was evaluated by analysing the binding of 199 TPO antibody- and
      MPO antibody-positive sera to TPO and MPO molecules. Sera from six patients with
      autoimmune thyroiditis (AITD) and four patients with systemic vasculitis (SV)
      with different TPO-MPO antibody findings were then chosen for further analyses.
      All six patients with AITD had TPO antibodies in enzyme immunoassay (EIA) and
      four of them had simultaneously MPO antibodies in EIA. In AITD patients antibody
      binding to TPO could not be inhibited by adding native MPO to the serum diluent,
      suggesting that the possible cross-reactive epitopes were exposed in the
      denaturated MPO molecule. Similarly, the MPO ab reactivity of patients with
      systemic vasculitis could not be inhibited by native TPO. To study whether TPO
      and MPO antibodies recognize linear epitopes, the binding of antibodies to
      synthetic TPO and MPO peptides was analysed. Several TPO and MPO peptides were
      reactive, including peptides reacting with both TPO and MPO antibody-positive
      sera. One of the most cross-reactive peptides contained AA 586-601 in TPO,
      showing also particularly high AA homology (88%) with MPO (AA 594-609). The
      results suggest that TPO and MPO molecules contain cross-reactive epitopes that
      are exposed in denaturated molecules and may thus cause false positive antibody
      findings in solid phase EIA assays.

PMID- 9246210
TI  - Immunotherapy affects the seasonal increase in specific IgE and interleukin-4 in
      serum of patients with seasonal allergic rhinitis.
AB  - This study was designed to determine seasonal changes in cytokines, soluble CD23
      and specific IgE in the serum of patients with seasonal allergic rhinitis, and
      the effect of immunotherapy on these seasonal changes. Fifty-four patients with
      seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a
      medication group and an immunotherapy group. The patients of the medication group
      were treated with non-sedating antihistamines alone during the pollen season. The
      patients of the immunotherapy group had been treated for variable periods (mean,
      5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum
      samples were collected before and during the pollen season from each patient, to
      determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and
      soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and
      a significant decrease in IFN-gamma were observed during the pollen season in the
      medication group. In contrast, in the immunotherapy group, none of specific IgE,
      IL-4 and IFN-gamma was significantly changed following natural exposure to
      pollens. However, these effects were not significant in patients undergoing
      immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE
      and IL-4 differed significantly between good responders and poor responders to
      immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal
      rate of increase in soluble CD23 was significantly correlated with a seasonal
      rate of increase in specific IgE, in both the medication and the immunotherapy
      groups. The seasonal rate of increase in soluble CD23 was significantly smaller
      in the good responders than in the poor responders to immunotherapy. In
      conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE,
      IL-4 and soluble CD23 in serum, and in addition switches the seasonal
      preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with
      treatment over several years. It is likely that the mechanisms responsible for
      the clinically beneficial effects of immunotherapy principally involve the
      modulation of Th-2 rather than Th-1 cytokines.

PMID- 9246212
TI  - IL-10 production and CD40L expression in patients with common variable
      immunodeficiency.
AB  - The authors studied CD40 ligant (CD40L) expression and interleukin-10 (IL-10)
      production in 16 patients with common variable immunodeficiency (CVI). Mean CD40L
      expression, determined by using cytofluorimetry, and measured as the mean
      fluorescence intensity following stimulation of peripheral blood mononuclear
      cells (PBMC) with phorbol myristate acetate (PMA) and calcium ionophore in 12
      patients, was comparable to that of controls. However, three CVI patients showed
      fluorescence intensity in stimulated cells below 2 standard deviations of normal
      donors' mean and two other patients had only a slight increase of stimulated
      versus unstimulated cells (< 10 channels). IL-10 production after stimulation of
      PBMC with both anti-CD3 or anti-CD3 plus PMA gave similar results in CVI patients
      and normal controls. In vitro stimulation of PBMC with anti-CD40 and various
      combinations of cytokines (IL-2, IL-4 and IL-10) induced IgG production above 100
      ng/ml in one CVI patient out of 13 tested. The data suggest that alterations of
      IL-10 production are unlikely to play a major role in the pathogenesis of
      impaired IgG production in most CVI patients. CD40L appears to be normally
      expressed in two thirds of CVI patients, but it may be functionally defective.

PMID- 9246213
TI  - Clinical progression of HIV infection: role of NK cells.
AB  - The purpose of the study was to examine how immune parameters related to non
      major histocompatibility complex (MHC) restricted cytotoxicity changed with
      respect to progression and duration of human immunodeficiency virus (HIV)
      infection. Forty-one HIV seropositive subjects with a known time for
      seroconversion were included. The major finding was that a low percentage and
      number of natural killer (NK) cells were found in the group who had a rapid
      progression to acquired immune deficiency syndrome (AIDS) (less than 70 months
      following seroconversion) compared with those progressing more slowly to AIDS
      (more than 70 months following seroconversion). Furthermore, a significant
      correlation was found between the number of months from seroconversion to the
      diagnosis of AIDS and percentages of CD16+ cells (rs = 0.811, P < 0.01), CD56+
      cells (rs = 0.647, P < 0.05), and CD16+CD56+ cells (rs = 0.839, P < 0.01) as well
      as the concentration of CD16+CD56+ cells in the blood (rs = 0.699, P < 0.05) No
      differences were found in percentages and concentrations of NK cell subsets
      between subjects with a long history (more than 6 years) versus a short history
      (less than 6 years) of HIV infection without AIDS. Furthermore, no negative
      correlations were found between the concentration of any NK subsets and the
      number of months since seroconversion in HIV seropositive individuals without
      AIDS. The total concentration of CD16+, CD56+, and CD16+CD56+ cells was lower in
      the group of HIV seropositive subjects compared with HIV seronegative subjects
      (age and sex matched), and the concentration of CD16+ cells was lower in those
      with AIDS than in those without AIDS. In conclusion, low concentration of NK
      cells in the blood was associated with a more rapid disease progression,
      indicating that defective non-MHC restricted cytotoxicity may be associated with
      HIV disease progression.

PMID- 9246214
TI  - IL-10 plays a role in the modulation of human granulomatous hypersensitivity
      against Schistosoma mansoni eggs induced by immune complexes.
AB  - It has been demonstrated that the chronic intestinal form of schistosomiasis is
      associated with the establishment and maintenance of a variety of
      immunoregulatory mechanisms that lead to a diminished granulomatous reaction to
      parasite eggs. Using an in vitro model of granuloma reaction we showed that
      immune complexes (IC) isolated from the sera of chronic intestinal
      schistosomiasis patients were able to reduce the granulomatous hypersensitivity
      (developed by peripheral blood mononuclear cells (PBMC) from schistosomiasis
      patients) to soluble egg antigen (SEA)-conjugated polyacrylamide beads (PB-SEA).
      This inhibitory activity, mediated by IC, was also observed in the proliferative
      response of PBMC stimulated with SEA and soluble worm antigen preparation (SWAP).
      Furthermore, we observed a decrease in TNF-alpha and an increase in IL-10
      production by PBMC treated with IC in an in vitro granuloma reaction. This
      phenomenon was also seen in a cell proliferation assay when PBMC were treated
      with IC and stimulated with S. mansoni antigens. These results demonstrate that
      circulating IC may down-regulate PBMC reactivity to S. mansoni antigens by
      changing the cytokine pattern produced by these cells.

PMID- 9246215
TI  - Gliadin specific, HLA DQ2-restricted T cells are commonly found in small
      intestinal biopsies from coeliac disease patients, but not from controls.
AB  - The authors have analysed gliadin specific, CD4+ T cells isolated from small
      intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free
      diet and three untreated) and nine control patients. The biopsies were stimulated
      ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells
      were positively selected with paramagnetic beads coated with an antibody against
      the interleukin-2 receptor. The T cells were expanded and tested for gliadin
      reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were
      recovered from biopsies of all 23 patients. Inhibition studies of T cell lines
      from 21 patients with anti-HLA monoclonal antibodies indicated predominant
      presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients
      (lines from seven patients with complete MoAb inhibition, the remaining with
      incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three
      patients. Nine gliadin specific T cell clones from six patients were established;
      all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in
      biopsies from the non-coeliac controls. Our findings demonstrate that gliadin
      reactive T cells are commonly found in the intestinal mucosa of CD patients and
      they support the notion that the majority of T cells recognize gliadin peptide(s)
      when presented by the disease associated DQ2 molecules.

PMID- 9246216
TI  - Analysis of 24-hour ECG in patients with panic disorder.
AB  - Previous evidence suggests an increased cardiovascular morbidity in patients with
      panic disorder. In this study, we compared 24-hour ECG in patients with panic
      disorder (n = 22; age: 36.1 +/- 7.6 years) and healthy controls (n = 21; age:
      34.6 +/- 10.0 years). The QTc intervals during the day or night were not
      significantly different between patients and controls. Ventricular ectopic beats
      were also not significantly different between the two groups. These results do
      not suggest any overt cardiac arrhythmias in this age group of patients with
      panic disorder.

PMID- 9246217
TI  - Iron treatment in children with attention deficit hyperactivity disorder. A
      preliminary report.
AB  - Iron plays a role in the regulation of dopaminergic activity. In the present
      study, nonanemic children with attention deficit hyperactivity disorder (ADHD)
      were evaluated with regard to heme and nonheme iron metabolism and the effect of
      short-term iron administration on behavior. The study group consisted of 14 boys
      aged 7-11 years. All first underwent testing to rule out other psychiatric and
      medical problems. The severity of the ADHD symptoms was determined by parent and
      teacher scores on the Connors Rating Scale. Thereafter, each patient received an
      iron preparation (Ferrocal), 5 mg/kg/day for 30 days. Blood samples were taken
      before and after drug administration. Results showed a significant increase in
      serum ferritin levels (from 25.9 +/- 9.2 to 44.6 +/- 18 ng/ml) and a significant
      decrease on the parents' Connors Rating Scale scores (from 17.6 +/- 4.5 to 12.7
      +/- 5.4). There were no changes in other blood parameters or in the teachers'
      scores on the rating scale. The effect of iron supplementation on the behavioral
      and cognitive symptoms in noniron-deficient ADHD children merits further
      investigation using a placebo-controlled study.

PMID- 9246218
TI  - Association of genes within the major histocompatibility complex with attention
      deficit hyperactivity disorder.
AB  - The objective was to determine whether a relationship exists among the complement
      C4B gene, a DR region gene and attention deficit hyperactivity disorder (ADHD).
      Thirty-one subjects with ADHD, their mothers, all but 5 of their fathers, and 90
      normal subjects living in northern Utah were studied. DR and C4B typing were
      performed by serologic HLA typing techniques and the DNA methods PCR-RFLP. The
      alleles of 2 genes, the null allele of the C4B gene and the beta 1 allele of the
      DR gene, encode for products involved in immune function and regulation. Each of
      these alleles was found to be significantly associated with ADHD. Moreover,
      approximately 55% of the ADHD subjects carried both of these alleles on 1 of
      their chromosomes, compared to only 8% of normal controls. Genes related to the
      immune system may be associated with development of the symptoms of ADHD.

PMID- 9246219
TI  - Significant decreases of ulinastatin-like immunoreactive substance in the
      cerebrospinal fluid of patients with dementia.
AB  - Studies to elucidate changes in the contents of ulinastatin-like immunoreactive
      substance (UTIRS) and alpha 1-microglobulin-like immunoreactive substance (alpha
      1 MIRS) in cerebrospinal fluid (CSF) of patients with dementia were performed.
      Levels of UTIRS in the dementia group were significantly (p < 0.01) lower than
      those in dementia-free subjects. In addition, lower levels of UTIRS were
      registered in subjects afflicted with a higher severity of dementia. However, the
      levels of alpha 1 MIRS were not affected in the dementia group compared with
      dementia-free subjects. Neither UTIRS nor alpha 1 MIRS contents were related to
      the existence and stages of Parkinson's disease. These results suggest that UTIRS
      levels in the CSF are associated with the severity of dementia.

PMID- 9246220
TI  - Auditory information processing in schizophrenia.
AB  - Early N1P2 and late N2P3 responses generated in an auditory oddball paradigm are
      topographically compared in three psychiatric patient groups. In schizophrenia N1
      and N2 amplitude is comparable with dementia and significantly decreased with
      respect to affective disorder. In contrast, P3 amplitude does not allow
      discriminating schizophrenia from affective disorder but is significantly
      diminished in dementia. The late N2P3 response shows a topographic effect along
      the fronto-occipital axis. Schizophrenia is characterized by an iCNV and N2
      maximum over the frontal planes and a compound P3 lacking distinct frontal and
      parietal components. The findings are discussed in reference to literature data
      and current hypotheses/theories concerning information processing. Our findings
      favour an important dysfunction of automatic processing including early selection
      in schizophrenia.

PMID- 9246221
TI  - Atypical neuroleptic malignant syndrome associated with clozapine treatment.
AB  - Clozapine is an atypical neuroleptic drug that was initially thought not to cause
      neuroleptic malignant syndrome (NMS). The authors report a case of NMS associated
      with clozapine use, developed in a patient without previous history of NMS.
      Considering that 13 such cases (including ours) have been reported so far, NMS
      should be considered in the differential diagnosis of a febrile patient treated
      with clozapine.

PMID- 9246222
TI  - Effect of chronic pretreatment with the sigma ligand JO 1784 on CRF-induced
      changes in behaviour, neurotransmitter and immunological function in the rat.
AB  - The effects of the chronic administration of the sigma ligand JO 1784 (igmesine)
      CRF-induced changes in some behavioural, immune, endocrine and neurotransmitter
      parameters were studied. In the elevated plus maze, CRF (1.0 microgram i.c.v.
      daily x 5 days) induced a reduction in the number of entries and time spent on
      the open arms was significantly attenuated by the sigma ligand JO 1784 (3 mg/kg x
      21 days) treatment. In the open field apparatus, the CRF-induced increase in the
      locomotor activity was also reduced by JO 1784 administration. JO 1784 treatment
      did not alter the concentration of the biogenic amine transmitters in the
      hypothalamus, nor reverse the increase in the turnover of serotonin and dopamine
      caused by CRF. JO 1784 treatment also failed to reverse a CRF-induced increase in
      the serum corticosterone, but it did reverse the reduction in phytohaemagglutinin
      and concanavalin A-induced lymphocyte proliferation caused by CRF but not the
      changes in the lymphocyte and neutrophil numbers caused by the peptide. These
      results demonstrate that JO 1784 has some antistress properties in CRF-treated
      rats.

PMID- 9246223
TI  - Endocrine correlates of personality traits: a comparison between emotionally
      stable and emotionally labile healthy young men.
AB  - An initial sample of 120 healthy young men was screened by a personality
      questionnaire and 15 subjects each with highest and lowest scores respectively on
      emotionality (emotionally labile, EL subjects and emotionally stable, ES
      subjects) were recruited for a study on the relationship between the degree of
      emotionality and the basal secretion of stress-sensitive hormones during night
      time. The nocturnal urinary excretion of cortisol, testosterone, adrenaline,
      noradrenaline and melatonin was measured over a period of 5 consecutive nights.
      The average amounts of each hormone excreted per night were not different between
      the two extreme groups. The variability of the excretion during the 5 nights of
      cortisol and testosterone, but not of adrenaline, noradrenaline and melatonin,
      was significantly higher in EL compared to ES subjects. The larger fluctuations
      in the nocturnal secretion of these two (and no other) hormones in EL subjects
      indicate that emotional lability is associated with a more labile regulation of
      cortisol and testosterone secretion. The observed intraindividual variability of
      basal stress hormone secretion may contribute to the vast interindividual
      variability noticed in psychoneuroendocrine stress research, especially in
      emotionally labile subjects.

PMID- 9246224
TI  - Comparison of the EEG effects of midazolam, thiopental, and propofol: the role of
      underlying oscillatory systems.
AB  - The EEG effects of 3 intravenous sedative drugs from different chemical families
      were studied during conscious sedation in 47 normal volunteers. The drugs studied
      were midazolam (a benzodiazepine), propofol (an alkylphenol) and thiopental (a
      barbiturate). Though these drugs cause different degrees of amnesia, they have
      the common EEG effects of suppressing alpha-rhythm and increasing total beta
      power. A large portion of the increase in beta-power can be accounted for by beta
      rhythms. We used the UNIFAC-EEG technique to differentiate oscillatory systems
      underlying the rhythms induced by these drugs in a quantitative fashion. While
      thiopental induced beta-rhythms which were similar to those appearing during
      drowsiness, midazolam and propofol induced beta-rhythms with substantially
      different characteristics. The differences between the beta-rhythms induced by
      drug infusion and previously described 'sleep spindles' are discussed. We
      conclude that a quantitative analysis of beta-rhythms can differentiate the
      effects of these drugs on the EEG.

PMID- 9246225
TI  - Comparison between conventional and neural network classifiers for rat sleep-wake
      stage discrimination.
AB  - This article describes an approach to selecting the most efficient classifier for
      rat sleep staging (waking, REM sleep and NREM sleep) discrimination. Three
      conventional (bayesian, linear, and euclidean) and two neural network (multilayer
      perceptrons integrating or not integrating contextual information) classifiers
      were compared. For each classifier, performances were presented in the form of a
      statistical concordance matrix comparing classifier results versus human expert
      results on 6 24-hour records (1 record per animal). Comparison between
      classifiers was based on the estimation and accuracy of global agreements.
      Interest was also focused on REM sleep state discrimination. The results show
      that neural network classifiers are appropriate tools to be integrated in an
      automatic rat sleep-wake stage system. The approach presented should help
      scientists in choosing a method of data classification.

PMID- 9246226
TI  - Useful web sites for researchers studying proteins.

PMID- 9246227
TI  - Animal models of anxiety: an ethological perspective.
AB  - In the field of anxiety research, animal models are used as screening tools in
      the search for compounds with therapeutic potential and as simulations for
      research on mechanism underlying emotional behaviour. However, a solely
      pharmacological approach to the validation of such tests has resulted in distinct
      problems with their applicability to systems other than those involving the
      benzodiazepine/GABAA receptor complex. In this context, recent developments in
      our understanding of mammalian defensive behaviour have not only prompted the
      development of new models but also attempts to refine existing ones. The present
      review focuses on the application of ethological techniques to one of the most
      widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh
      approach to an established test has revealed a hitherto unrecognized
      multidimensionality to plus-maze behaviour and, as it yields comprehensive
      behavioural profiles, has many advantages over conventional methodology. This
      assertion is supported by reference to recent work on the effects of diverse
      manipulations including psychosocial stress, benzodiazepines, GABA receptor
      ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic
      agents. On the basis of this review, it is suggested that other models of anxiety
      may well benefit from greater attention to behavioural detail.

PMID- 9246228
TI  - Evolution of circadian organization in vertebrates.
AB  - Circadian organization means the way in which the entire circadian system above
      the cellular level is put together physically and the principles and rules that
      determine the interactions among its component parts which produce overt rhythms
      of physiology and behavior. Understanding this organization and its evolution is
      of practical importance as well as of basic interest. The first major problem
      that we face is the difficulty of making sense of the apparently great diversity
      that we observe in circadian organization of diverse vertebrates. Some of this
      diversity falls neatly into place along phylogenetic lines leading to firm
      generalizations: i) in all vertebrates there is a "circadian axis" consisting of
      the retinas, the pineal gland and the suprachiasmatic nucleus (SCN), ii) in many
      non-mammalian vertebrates of all classes (but not in any mammals) the pineal
      gland is both a photoreceptor and a circadian oscillator, and iii) in all non
      mammalian vertebrates (but not in any mammals) there are extraretinal (and
      extrapineal) circadian photoreceptors. An interesting explanation of some of
      these facts, especially the differences between mammals and other vertebrates,
      can be constructed on the assumption that early in their evolution mammals passed
      through a "nocturnal bottleneck". On the other hand, a good deal of the diversity
      among the circadian systems of vertebrates does not fall neatly into place along
      phylogenetic lines. In the present review we will consider how we might better
      understand such "phylogenetically incoherent" diversity and what sorts of new
      information may help to further our understanding of the evolution of circadian
      organization in vertebrates.

PMID- 9246229
TI  - Calcium handling by vascular myocytes in hypertension.
AB  - Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of
      free intracellular Ca2+ within the myocyte is precisely regulated by
      sequestration and extrusion mechanisms. Extensive evidence indicates that a
      defect in the regulation of intracellular Ca2+ plays a role in the augmented
      vascular reactivity characteristic of clinical and experimental hypertension. For
      example, arteries from spontaneously hypertensive rats (SHR) have an increased
      contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are
      elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes
      are due to an increase in membrane Ca2+ channel density and possibly function in
      vascular myocytes from hypertensive animals. Several observations using various
      experimental approaches support this hypothesis: 1) the contractile activity in
      response to depolarizing stimuli is increased in arteries from hypertensive
      animals demonstrating increased voltage-dependent Ca2+ channel activity in
      hypertension; 2) Ca2+ channel agonists such as Bay K 8644 produce contractions in
      isolated arterial segments from hypertensive rats and minimal contraction in
      those from normotensive rats; 3) intracellular Ca2+ concentration is abnormally
      increased in vascular myocytes from hypertensive animals following treatment with
      Ca2+ channel agonists and depolarizing interventions, and 4) using the voltage
      clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive
      rats is nearly twice as large as that from myocytes of normotensive rats. We
      suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+
      channel density, resulting from increased channel synthesis or reduced turnover,
      underlies the increased vascular reactivity characteristic of hypertension.

PMID- 9246230
TI  - Control of the phosphorylation of the astrocyte marker glial fibrillary acidic
      protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions:
      possible key factor in astrocytic plasticity.
AB  - The present review describes recent research on the regulation by glutamate and
      Ca2+ of the phosphorylation state of the intermediate filament protein of the
      astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature
      hippocampal slices. The results of this research are discussed against a
      background of modern knowledge of the functional importance of astrocytes in the
      brain and of the structure and dynamic properties of intermediate filament
      proteins. Astrocytes are now recognized as partners with neurons in many aspects
      of brain function with important roles in neural plasticity. Site-specific
      phosphorylation of intermediate filament proteins, including GFAP, has been shown
      to regulate the dynamic equilibrium between the polymerized and depolymerized
      state of the filaments and to play a fundamental role in mitosis. Glutamate was
      found to increase the phosphorylation state of GFAP in hippocampal slices from
      rats in the post-natal age range of 12-16 days in a reaction that was dependent
      on external Ca2+. The lack of external Ca2+ in the absence of glutamate also
      increased GFAP phosphorylation to the same extent. These effects of glutamate and
      Ca2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP
      was completely Ca(2+)-dependent. Studies using specific agonists of glutamate
      receptors showed that the glutamate response was mediated by a G protein-linked
      group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not
      act by liberating Ca2+ from internal stores, it is proposed that activation of
      the receptor by glutamate inhibits Ca2+ entry into the astrocytes and
      consequently down-regulates a Ca(2+)-dependent dephosphorylation cascade
      regulating the phosphorylation state of GFAP. The functional significance of
      these results may be related to the narrow developmental window when the
      glutamate response is present. In the rat brain this window corresponds to the
      period of massive synaptogenesis during which astrocytes are known to
      proliferate. Possibly, glutamate liberated from developing synapses during this
      period may signal an increase in the phosphorylation state of GFAP and a
      consequent increase in the number of mitotic astrocytes.

PMID- 9246231
TI  - Genomic characterization of Brazilian hepatitis C virus genotypes 1a and 1b.
AB  - Parts of 5' non-coding (5' NC) and of E1 envelope regions of the hepatitis C
      virus (HCV) genome were amplified from sera of 26 Brazilian anti-HCV antibody
      positive patients using the reverse transcription-polymerase chain reaction (RT
      PCR). Fourteen samples were PCR positive with primers from the 5' NC region and 8
      of them were also positive with primers from the E1 region. A genomic segment of
      176 bp from the E1 region of 7 isolates was directly sequenced from PCR products.
      The sequences were compared with those of HCV strains isolated in other countries
      and the Brazilian isolates were classified by phylogenetic analysis into
      genotypes 1a and 1b. This could have a clinical importance since it has been
      shown that individuals infected with type 1 viruses are less likely to respond to
      treatment with interferon than individuals infected with types 2 and 3 viruses.
      Two quasispecies isolated from the same patient with an interval of 13 months
      differed by two base substitutions (1.1%). The sequence of another isolate
      presented a three-nucleotide deletion at codon 329.

PMID- 9246232
TI  - Assessment of the degree of contamination of rat germ cell preparations using
      specific cDNA probes.
AB  - Recent reports showing a decrease in sperm count in men have brought new concerns
      about male infertility. Animal models have been widely used to provide some
      relevant information about the human male gamete, and extrapolations are made to
      men and to the clinical context. The present-study assesses one of the methods
      used for separation of germ cells of the adult rat testis, namely centrifugal
      elutriation followed by density gradients (Percoll). This method was chosen since
      it presents the best results for cell purity in separating germ cells from the
      rat testis. A comparison between continuous and discontinuous Percoll gradients
      was performed in order to identify the best type of gradient to separate the
      cells. Maximal cell purity was obtained for spermatocytes (81 +/- 8.2%, mean +/-
      SEM) and spermatids (84 +/- 2.6%) using centrifugal elutriation followed by
      continuous Percoll gradients. A significant difference in purity was observed
      between elongating spermatids harvested from continuous Percoll gradients and
      from discontinuous gradients. Molecular analysis was used to assess cell
      contamination by employing specific probes, namely transition protein 2 (TP2),
      mitochondrial cytochrome C oxidase II (COX II), and sulfated glycoprotein 1
      (SGP1). Molecular analysis of the samples demonstrated that morphological
      criteria are efficient in characterizing the main composition of the cell
      suspension, but are not reliable for identifying minimal contamination from other
      cells. Reliable cell purity data should be established using molecular analysis.

PMID- 9246233
TI  - Synergistic effect of glucose and prolactin on GLUT2 expression in cultured
      neonatal rat islets.
AB  - We studied the synergistic effect of glucose and prolactin (PRL) on insulin
      secretion and GLUT2 expression in cultured neonatal rat islets. After 7 days in
      culture, basal insulin secretion (2.8 mM glucose) was similar in control and PRL
      treated islets (1.84 +/- 0.06% and 2.08 +/- 0.07% of the islet insulin content,
      respectively). At 5.6 and 22 mM glucose, insulin secretion was significantly
      higher in PRL-treated than in control islets, achieving 1.38 +/- 0.15% and 3.09
      +/- 0.21% of the islet insulin content in control and 2.43 +/- 0.16% and 4.31 +/-
      0.24% of the islet insulin content in PRL-treated islets, respectively. The
      expression of the glucose transporter GLUT2 in B-cell membranes was dose
      dependently increased by exposure of the islet to increasing glucose
      concentrations. This effect was potentiated in islets cultured for 7 days in the
      presence of 2 micrograms/ml PRL. At 5.6 and 10 mM glucose, the increase in GLUT2
      expression in PRL-treated islets was 75% and 150% higher than that registered in
      the respective control. The data presented here indicate that insulin secretion,
      induced by different concentrations of glucose, correlates well with the
      expression of the B-cell-specific glucose transporter GLUT2 in pancreatic islets.

PMID- 9246234
TI  - Mini-Mu insertions in the tetracycline resistance determinant from Proteus
      mirabilis.
AB  - The inducible tetracycline resistance determinant isolated from Proteus mirabilis
      cloned into the plasmid pACYC177 was mutagenized by insertion of a mini-Mu-lac
      phage in order to define the regions in the cloned sequences encoding the
      structural and regulatory proteins. Three different types of mutants were
      obtained: one lost the resistance phenotype and became Lac+; another expressed
      the resistance at lower levels and constitutively; the third was still dependent
      on induction but showed a lower minimal inhibitory concentration. The mutant
      phenotypes and the locations of the insertions indicate that the determinant is
      composed of a repressor gene and a structural gene which are not transcribed
      divergently as are other known tetracycline determinants isolated from Gram
      negative bacteria.

PMID- 9246235
TI  - Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted
      to cardiopulmonary bypass.
AB  - Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or
      endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients
      submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3
      females and 7 males aged 65 +/- 11 years, 74 +/- 16 kg body weight, 166 +/- 9 cm
      height and 1.80 +/- 0.21 m2 body surface area (BSA), and control, 14 surgical
      patients not submitted to CPB, 11 female and 3 males aged 41 +/- 14 years, 66 +/-
      14 kg body weight, 159 +/- 9 cm height and 1.65 +/- 0.16 m2 BSA (mean +/- SD).
      Sodium diclofenac (1 mg/kg, im Voltaren 75 twice a day) was administered to
      patients in the Recovery Unit 48 h after surgery. Venous blood samples were
      collected during a period of 0-12 h and analgesia was measured by the visual
      analogue scale (VAS) during the same period. Plasma diclofenac levels were
      measured by high performance liquid chromatography. A two-compartment open model
      was applied to obtain the plasma decay curve and to estimate kinetic parameters.
      Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels
      were increased five-fold in CPB patients. Data obtained for analgesia reported as
      the maximum effect (EMAX) were: 25% VAS (CPB) vs 10% VAS (control), P < 0.05,
      median measured by the visual analogue scale where 100% is equivalent to the
      highest level of pain. To correlate the effect versus plasma diclofenac levels,
      the EMAX sigmoid model was applied. A prolongation of the mean residence time for
      maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in
      spite of the reduced analgesia reported for these patients, during the time-dose
      interval. In conclusion, the extent of plasma diclofenac protein binding was
      influenced by CPB with clinically relevant kinetic-dynamic consequences.

PMID- 9246236
TI  - Modification of pyruvate kinase and lactate dehydrogenase in foot muscle of the
      sea mussel Mytilus galloprovincialis under anaerobiosis and recovery.
AB  - The modification of pyruvate kinase (PK) and lactate dehydrogenase (LDH) activity
      in foot muscle of the mussel Mytilus galloprovincialis during exposure to air and
      recovery in water was investigated. In the course of exposure to air, the
      activity of these enzymes measured at high and low substrate concentrations
      showed successive increases and decreases. Returning the mussels to water after
      exposure to air affected enzyme activity in a manner similar to anaerobiosis.
      When measuring at saturated concentrations of substrates and substrate and
      coenzyme for PK and LDH, respectively, the maximum activation of PK (37%) was
      observed at 4 h of animal exposure to air, and for LDH (67%) at 6 h exposure to
      air. During 24 h of exposure of animals to air, PK activity practically reached
      the stock level, while LDH was still activated (148%). The change in lactate
      dehydrogenase activity in mussel muscle during anoxia and recovery is described
      here for the first time. Variation in pyruvate kinase activity during exposure to
      air and recovery is linked to the alteration of half-maximal saturation constants
      and maximal velocity for both substrates. The possible role of reversible
      phosphorylation in the regulation of pyruvate kinase and lactate dehydrogenase
      properties is discussed.

PMID- 9246237
TI  - Proteolytic release and partial characterization of human sperm-surface
      glycopeptides.
AB  - Sperm-surface glycopeptides were obtained from intact sperm membranes after
      proteolytic release by different enzymatic treatments such as autoproteolysis,
      trypsin, papain and pronase. Glycopeptides were isolated, their properties and
      composition were examined, and their monosaccharide and amino acid constituents
      were characterized. The monosaccharides identified were fucose, mannose,
      galactose, N-acetylglucosamine, and N-acetylgalactosamine, which form part of
      more than one type of oligosaccharide units. Autoproteolytic treatment mainly
      provided O-glycosidic type oligosaccharides, while a mixture of O- and N
      glycosidic oligosaccharides was obtained in variable proportions when treated
      with trypsin, papain or pronase. The highest degree of peptide cleavage was
      obtained with pronase. Despite the higher yields reached with trypsin, these
      glycopeptides contain the lowest percentage of oligosaccharide chains.
      Proteolytic treatment provides a simple, rapid procedure for the isolation of
      glycopeptides from the sperm surface.

PMID- 9246238
TI  - Glycosphingolipid antigens from Leishmania (L.) amazonensis amastigotes. Binding
      of anti-glycosphingolipid monoclonal antibodies in vitro and in vivo.
AB  - Specific glycosphingolipid antigens of Leishmania (L.) amazonensis amastigotes
      reactive with the monoclonal antibodies (MoAbs) ST-3, ST-4 and ST-5 were
      isolated, and their structure was partially elucidated by negative ion fast atom
      bombardment mass spectrometry. The glycan moieties of five antigens presented
      linear sequences of hexoses and N-acetylhexosamines ranging from four to six
      sugar residues, and the ceramide moieties were found to be composed by a
      sphingosine d18:1 and fatty acids 24:1 or 16:0. Affinities of the three
      monoclonal antibodies to amastigote glycosphingolipid antigens were also analyzed
      by ELISA. MoAb ST-3 reacted equally well with all glycosphingolipid antigens
      tested, whereas ST-4 and ST-5 presented higher affinities to glycosphingolipids
      with longer carbohydrate chains, with five or more sugar units (slow migrating
      bands on HPTLC). Macrophages isolated from footpad lesions of BALB/c mice
      infected with Leishmania (L.) amazonensis were incubated with MoAb ST-3 and, by
      indirect immunofluorescence, labeling was only detected on the parasite, whereas
      no fluorescence was observed on the surface of the infected macrophages,
      indicating that these glycosphingolipid antigens are not acquired from the host
      cell but synthesized by the amastigote. Intravenous administration of 125I
      labeled ST-3 antibody to infected BALB/c mice showed that MoAb ST-3 accumulated
      significantly in the footpad lesions in comparison to blood and other tissues.

PMID- 9246239
TI  - Association between polyclonal B cell activation and the presence of
      autoantibodies in mice infected with Yersinia enterocolitica O:3.
AB  - Eight-week old conventional female Swiss mice were inoculated intravenously with
      Yersinia enterocolitica O:3. A second group of normal mice was used as control.
      Five mice from each group were bled by heart puncture and their spleens were
      removed for spleen cell collection on the 3rd, 5th, 7th, 10th, 14th and 21st day
      after infection. Immunoglobulin-secreting spleen cells were detected by the
      isotype-specific protein A plaque assay. Total immunoglobulin levels were
      determined in mouse serum by single radial immunodiffusion and the presence of
      autoantibodies was determined by ELISA. We observed a marked increase in the
      total number of cells secreting immunoglobulins of all isotypes as early as on
      the 3rd day post-infection and the peak of secretion occurred on the 7th day. At
      the peak of the immunoglobulin response, the total number of secreting cells was
      19 times higher than that of control mice and most immunoglobulin-secreting cells
      were of the IgG2a isotype. On the 10th day post-infection, total serum
      immunoglobulin values were 2 times higher in infected animals when compared to
      the control group, and continued at this level up to the 21st day post-infection.
      Serum absorption with viable Y. enterocolitica cells had little effect on
      antibody levels detected by single radial immunodiffusion. Analysis of serum
      autoantibody levels revealed that Y. enterocolitica infection induced an increase
      of anti-myosin and anti-myelin immunoglobulins. The sera did not react with
      collagen. The present study demonstrates that Y. enterocolitica O:3 infection
      induces polyclonal activation of murine B cells which is correlated with the
      activation of some autoreactive lymphocyte clones.

PMID- 9246240
TI  - Response threshold to aversive stimuli in stimulated early protein-malnourished
      rats.
AB  - Two animal models of pain were used to study the effects of short-term protein
      malnutrition and environmental stimulation on the response threshold to aversive
      stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to
      malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age
      while the mothers of the other half (controls) were well nourished, receiving 16%
      protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the
      animals in the malnourished and control groups were maintained under stimulating
      conditions, including a 3-min daily handling from 0 to 70 days and an enriched
      living cage after weaning. The other half was reared in a standard living cage.
      At 70 days, independent groups of rats were exposed to the shock threshold or to
      the tail-flick test. The results showed lower body and brain weights in
      malnourished rats when compared with controls at weaning and testing. In the
      shock threshold test the malnourished animals were more sensitive to electric
      shock and environmental stimulation increased the shock threshold. No differences
      due to diet or environmental stimulation were found in the tail-flick procedure.
      These results demonstrate that protein malnutrition imposed only during the
      lactation period is efficient in inducing hyperreactivity to electric shock and
      that environmental stimulation attenuates the differences in shock threshold
      produced by protein malnutrition.

PMID- 9246241
TI  - Atherosclerosis and acute arterial thrombosis in rabbits: a model using balloon
      desendothelization without dietary intervention.
AB  - Acute thrombosis can be induced in rabbits by a triggering protocol using
      Russell's viper venom and histamine given after 8 months of a 1% cholesterol diet
      and balloon desendothelization. In the present study, we tested the hypothesis
      that aortic desendothelization performed 4 months before the triggering protocol
      without a high cholesterol diet is a highly effective and less expensive way of
      producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand
      white rabbits on a normal diet were studied. The control group (N = 9) received
      no intervention during the 4-month observation period, while the other group (N =
      10) was submitted to aortic balloon desendothelization using a 4F Fogarty
      catheter. At the end of this period, all animals were killed 48 h after receiving
      the first dose of the triggering treatment. Eight of 10 rabbits (80%) in the
      balloon-trauma group presented platelet-rich arterial thrombosis while none of
      the animals in the control group had thrombus formation (P < 0.01). Thus, this
      model, using balloon desendothelization without dietary manipulation, induces
      arterial atherosclerosis and thrombosis and may provide possibilities to test new
      therapeutic approaches.

PMID- 9246242
TI  - Lead (Pb2+) and cadmium (Cd2+) inhibit the dipsogenic action of central beta
      adrenergic stimulation by isoproterenol.
AB  - We have previously demonstrated that acute third ventricle injections of both
      Pb2+ and Cd2+ impair the dipsogenic response elicited by three different
      situations: dehydration and central cholinergic or angiotensinergic stimulation.
      beta-Adrenergic activation is part of the multifactorial integrated systems
      operating in drinking behavior control in the central nervous system. In the
      present study acute third ventricle injections of Pb2+ (3, 30 and 300 pmol/rat)
      or Cd2+ (0.3, 3 and 30 pmol/ rat) blocked the dipsogenic response induced by
      third ventricle injections of isoproterenol (ISO; 160 nmol/rat) in a dose
      dependent manner. Normohydrated animals receiving ISO + NaAc (sodium acetate) or
      saline (controls) displayed a high water intake after 120 min (ISO+saline = 5.78
      +/- 0.54 ml/100 g; ISO+NaAc = 6.00 +/- 0.6 ml/100 g). After the same period,
      animals receiving ISO but pretreated with PbAc at the highest dose employed (300
      pmol/rat) drank 0.78 +/- 0.23 ml/100 g while those receiving ISO and pretreated
      with the highest dose of CdCl2 (30 pmol/rat) presented a water intake of 0.7 +/-
      0.30 ml/100 g. Third ventricle injections of CdCl2 (3 nmol/rat) or PbAc (3
      nmol/rat) did not modify food intake in rats deprived of food for 24 h. Thus,
      general central nervous system depression explaining the antidipsogenic action of
      the metals can be safely excluded. It is concluded that both Pb2+ and Cd2+
      inhibit water intake induced by central beta-adrenergic stimulation.

PMID- 9246243
TI  - Fighting schizophrenia and its stigma. A new World Psychiatric Association
      educational programme.

PMID- 9246244
TI  - BSE and human prion disease.

PMID- 9246245
TI  - The Hampstead Schizophrenia Survey 1991. I: Prevalence and service use
      comparisons in an inner London health authority, 1986-1991.
AB  - BACKGROUND: A point prevalence study of schizophrenia was carried out in 1986 in
      the former Hampstead Health District using a key informant method to identify
      cases. The point prevalence of broadly defined schizophrenia was 4.7 per 1000.
      METHOD: A repeat census of people with schizophrenia, using the same method, was
      carried out in 1991 and the point prevalence calculated. The accuracy of the
      census method was estimated. Contact with services, social and occupational
      activity, and medication usage in the 1986 and 1991 samples were compared.
      RESULTS: The point prevalence rate of broadly defined schizophrenia in 1991 was
      5.1 per 1000. The results of both censuses showed we underestimated the number of
      individuals with DSM-III-R positive schizophrenia by about 14%. The level of
      contact with specialist services was greater in 1991 than 1986. Patients in 1991
      were discharged on higher doses of medication, and their most recent admission
      was more likely to be due to non-compliance, than the 1986 group. CONCLUSION: The
      point prevalence confirmed the high rate reported in 1986. The accuracy of the
      census was within acceptable limits for service planning. Contact with specialist
      services increased between 1986 and 1991.

PMID- 9246246
TI  - The Hampstead Schizophrenia Survey 1991. II: Incidence and migration in inner
      London.
AB  - BACKGROUND: The previous paper reports a high prevalence of schizophrenia (broad
      definition) in an inner London area. In this paper we test hypotheses for this
      finding and examine the characteristics of people with schizophrenia who move
      frequently. METHOD: People with schizophrenia in the Hampstead area were
      identified by key informant methodology, at two censuses five years apart. This
      allowed identification of incident cases during these five years and
      identification of people who had moved into and out of the area. RESULTS: The
      incidence of DSM-III-R schizophrenia in Hampstead between 1986 and 1991 was at
      least 0.21 per 1000 of the population aged 15 to 54. There was a significant
      movement of people with schizophrenia to this inner London area from outer London
      between 1986 and 1991. People with schizophrenia who were relatively mobile were
      significantly more likely to be male, to suffer with prominent hallucinations,
      and to have no contact with a GP. CONCLUSIONS: The high prevalence of broad
      schizophrenia in this inner London area is, in part, due to geographical drift. A
      significant excess of the people with schizophrenia who move frequently are men
      with positive symptoms.

PMID- 9246247
TI  - Access to mental health care in an inner-city health district. I: Pathways into
      and within specialist psychiatric services.
AB  - BACKGROUND: Needs for mental health care are likely to be high in urban areas.
      Purchasers must assess the extent to which these are being met. The pathways to
      care model provides a framework for this purpose. METHOD: Epidemiological surveys
      of adults living in deprived multi-ethnic inner-city catchment area were
      undertaken in psychiatric services, primary care and community settings.
      Estimated prevalence rates were calculated and the association between clinical
      and demographic factors and the use of psychiatric services examined. RESULTS:
      Around a third of people with mental health problems did not consult a GP, and
      half failed to have their problems recognised by their doctor. Access to
      psychiatric services and especially to inpatient care was highly restricted.
      Diagnosis and ethnicity had a marked influence on the use of specialist services.
      CONCLUSIONS: Many people with psychiatric morbidity are not receiving treatment
      either from primary care or specialist services. High levels of severe morbidity
      and compulsory admissions highlight the pressures placed on inner-city
      psychiatric services.

PMID- 9246248
TI  - Access to mental health care in an inner-city health district. II: Association
      with demographic factors.
AB  - BACKGROUND: In addition to clinical and service factors, planners need to take
      account of the influence of demographic variables, especially ethnicity, on
      access to mental health care. METHOD: Estimated prevalence rates were calculated
      from epidemiological surveys undertaken in three settings: psychiatric services,
      primary care and the general population. Associations between demographic factors
      and service use were examined using the 'pathways to care' model. RESULTS:
      Considerable differences in access to mental health care were found, particularly
      according to ethnicity. The major impediment to Asians accessing care occurred at
      the interface between primary and secondary care, whereas the most striking
      feature for Blacks was the poor level of case recognition by GPs. CONCLUSIONS: In
      order to improve the uptake of mental health care, new initiatives should target
      those who are most likely to be unwell but least likely to access services.
      Purchasers and providers need to address differential patterns of use when
      developing and reviewing services.

PMID- 9246249
TI  - The predictive validity of a diagnosis of schizophrenia. A report from the
      International Study of Schizophrenia (ISoS) coordinated by the World Health
      Organization and the Department of Psychiatry, University of Nottingham.
AB  - BACKGROUND: Outcome is important in the validation of psychiatric diagnosis, as
      most disorders lack clinicopathological correlates. We describe the predictive
      validity of four definitions of schizophrenia (DSM-III-R, ICD-10, ICD-9 and
      CATEGO S+), in a representative cohort of patients selected during their first
      episode of psychosis. METHOD: Each definition of schizophrenia was applied to 99
      patients. Their respective ability to predict 13-year outcome (Global Assessment
      of Functioning scales) was assessed. RESULTS: DSM-III-R and ICD-10 diagnoses of
      schizophrenia have high predictive validity for long-term outcome, and both
      provide relatively stable diagnoses. ICD-9 is reasonably good at predicting
      disability, but not symptoms, and CATEGO S+ showed no predictive validity. Adding
      six-month duration criteria to ICD-10, ICD-9 and CATEGO S+ improved their
      predictive validity, and removing the six-month duration criterion from DSM-III-R
      commensurately reduced predictive validity. CONCLUSIONS: Modern diagnostic
      systems (DSM-III-R and ICD-10) have high predictive validity, and are superior to
      ICD-9. The six-month duration criterion of DSM-III-R schizophrenia accounts for
      its predictive validity and stability over 13 years, but restricts its use in
      first-episode studies. The one-month duration criterion of ICD-10 is less
      restrictive, without major compromises in predictive validity or stability.

PMID- 9246250
TI  - The Maudsley Family Study. 4. Normal planum temporale asymmetry in familial
      schizophrenia. A volumetric MRI study.
AB  - BACKGROUND: Loss or reversal of the normal asymmetry of the planum temporale (PT)
      has been reported in schicophrenia, and may be due to aberations in the gene(s)
      controlling the development of brain asymmetries. We tested this hypothesis in a
      sample of schizophrenics and their relatives from families multiply affected with
      the disorder. METHOD: We compared 32 schizophrenics and 55 of their non
      schizophrenic first-degree relatives with 39 matched community controls.
      Volumetric measurements of the cortical volume beneath the PT were obtained using
      the Cavalieri method from three-dimensionally reconstructed magnetic resonance
      imaging images. RESULTS: PT volume asymmetry coefficients from patients and their
      relatives did not differ significantly from those of the controls. Gender
      specific analysis did not revealany differences. CONCLUSIONS: Abnormalities in PT
      volume asymmetry are not present in familial schizophrenia, where genetic factors
      appear to predominate.

PMID- 9246251
TI  - The Nithsdale Schizophrenia Surveys. 16. Breast-feeding and schizophrenia:
      preliminary results and hypotheses.
AB  - BACKGROUND: Schizophrenia may in some cases be a neurodevelopmental disorder.
      Breast milk is important to the developing brain. Might a lack of breast milk be
      an environmental risk factor in schizophrenia? METHOD: Mothers of 45
      schizophrenic patients in Nithsdale, southwest Scotland, completed a
      questionnaire about whether or not their offspring had been breast-fed. RESULTS:
      The incidence of breast-feeding in patients was 29% and in sibs 38%. Most
      patients were born in the 1940s and 1950s. The incidence in patients born in
      these two decades, 33 and 26%, respectively, was significantly lower than in
      Scottish surveys in 1946 (81%) and 1958 (51%). Those patients who had not been
      breast-fed had more schizoid and schizotypal personality traits in childhood and
      a poorer social adjustment than their sibs; breast-fed patients did not differ
      from their sibs. CONCLUSIONS: Fewer schizophrenic patients than normal were
      breast-fed. Lack of breast milk may be a risk factor in the neurodevelopmental
      form of schizophrenia.

PMID- 9246252
TI  - The treatment of sexually dysfunctional men without partners: a controlled study
      of three behavioural group approaches.
AB  - BACKGROUND: Models of sex therapy for sexual dysfunction in single men are
      available, but their value is not well established. This controlled study
      compared three approaches to the treatment of sexually dysfunctional single men.
      METHOD: Sixty-nine single men diagnosed as sexually dysfunctional were randomly
      assigned to treatments focusing on either their sexual dysfunction, their
      interpersonal problems, a combination of both or a waiting list; 51 completed
      treatment and 50 the one-year follow-up. Treatment was administered in small
      groups in 15 weekly sessions and four six-weekly sessions during the first six
      months of a year-long follow-up. RESULTS: No clinically meaningful change was
      observed during the waiting period. In contrast, a significant and equivalent
      improvement was observed in all treatment groups by the end of treatment.
      However, differences between them were in evidence at 6 and 12 months' follow-up.
      CONCLUSIONS: Both treatments paying attention to the patients' interpersonal
      difficulties resulted in significantly better outcomes overall than the approach
      that concentrated on problems in sexual functioning alone.

PMID- 9246253
TI  - Controlled efficacy study of fluoxetine in dysthymia.
AB  - BACKGROUND: There have been very few controlled studies of antidepressants in
      dysthymia, particularly in samples diagnosed reliably and with an adequate length
      of follow-up. In this investigation, we measured the long-term outcome in a large
      group of patients meeting DSM-III-R criteria for dysthymia. This study was
      designed to investigate whether fluoxetine is effective in the treatment of
      dysthymia. METHOD: This randomised study including 140 patients, compared
      fluoxetine (91 patients) and placebo (49 patients) on a double-blind basis in two
      distinct phases: a short-term end-point (3 months with 20 mg/day fluoxetine) and
      a medium-term end-point (6 months) where the initial responders continued double
      blind treatment unchanged and non-responders received an additional treatment of
      20 mg/day fluoxetine. RESULTS: After three months of treatment, response was seen
      more frequently in the fluoxetine group (42/72) than in the placebo group (14/39,
      P < 0.0001). Improved patients at 3 months were still improved at 6 months.
      Furthermore, 50% of the nonresponders at 3 months improved and rated as
      responders at 6 months, after fluoxetine was increased to 40 mg daily.
      CONCLUSIONS: This study showed the significant and persistent action of
      fluoxetine on dysthymia. The finding that 50% of the non-responders at 3 months
      were improved at 6 months, after fluoxetine dosage was increased to 40 mg daily,
      argues in favour of treating dysthymic patients for at least 6 months, and with a
      higher dosage if the initial doses are ineffective.

PMID- 9246254
TI  - Anxiety, depression and PTSD in asylum-seekers: assocations with pre-migration
      trauma and post-migration stressors.
AB  - BACKGROUND: Research into the mental health of refugees has burgeoned in recent
      times, but there is a dearth of studies focusing specifically on the factors
      associated with psychiatric distress in asylum-seekers who have not been accorded
      residency status. METHOD: Forty consecutive asylum-seekers attending a community
      resource centre in Sydney, Australia, were interviewed using structured
      instruments and questionnaires. RESULTS: Anxiety scores were associated with
      female gender, poverty, and conflict with immigration officials, while loneliness
      and boredom were linked with both anxiety and depression. Thirty subjects (79%)
      had experienced a traumatic event such as witnessing killings, being assaulted,
      or suffering torture and captivity, and 14 subjects (37%) met full criteria for
      PTSD. A diagnosis of PTSD was associated with greater exposure to pre-migration
      trauma, delays in processing refugee applications, difficulties in dealing with
      immigration officials, obstacles to employment, racial discrimination, and
      loneliness and boredom. CONCLUSIONS: Although based on correlational data derived
      from'a convenient' sample, our findings raise the possibility that current
      procedures for dealing with asylum-seekers may contribute to high levels of
      stress and psychiatric symptoms in those who have been previously traumatised.

PMID- 9246255
TI  - Road traffic accidents: early psychological consequences in children and
      adolescents.
AB  - BACKGROUND: Although road traffic accidents are a major cause of injury and death
      in children and adolescents, research into their psychological consequences
      consists mainly of case reports. METHOD: A prospective study was made of young
      road traffic accident victims: 57 subjects, aged 5-18 years, who had been injured
      in road traffic accidents, and their parents, were interviewed 2-16 days post
      accident and re-examined after 12-15 weeks. RESULTS: Post-accident stress
      symptoms occurred at both times. There was a decrease of symptom severity between
      the two interviews, but at the later time, 14% still suffered from moderate or
      severe post-traumatic stress disorder, 17% from serious traffic-related fears,
      and parents reported increased mood disturbance in their children compared with
      the pre-accident period. High levels of distress during and immediately after the
      accident were associated with severe post-traumatic stress symptoms. CONCLUSIONS:
      There is an urgent need for healthcare staff working with children and
      adolescents involved in road traffic accidents to be aware of the potential
      psychological consequences and the importance of the immediate accident
      experience on subsequent coping.

PMID- 9246256
TI  - Empirically based subgrouping of eating disorders in adolescents: a longitudinal
      perspective.
AB  - BACKGROUND: Successive DSM versions struggle with the heterogeneity of the eating
      disorders. Criteria were mainly based on clinical impressions and on descriptive
      and inferential studies. METHOD: In a study of 55 eating-disordered adolescents,
      we investigated whether patients could be grouped on an empirical basis, using
      principal components analysis (PCA) with optimal scoring (scaling), i.e. PCA with
      no a priori assumptions. Clustering was based on Morgan-Russell subscales, each
      measured four times over the course of illness. RESULTS: Contrary to DSM-IV
      criteria, patients did not cluster primarily on the basis of anorectic symptoms;
      the occurrence of bulimic symptoms was more dominant. Core symptomatology
      (preoccupation with food, disturbed body perception and inadequate sexual
      behaviour) did not differ between patients, either at referral or over time.
      CONCLUSIONS: These results support the spectrum hypothesis of the eating
      disorders, which considers them as one syndrome with different manifestations.

PMID- 9246257
TI  - Symptom severity and cognitive impairment in chronically hospitalised geriatric
      patients with affective disorders.
AB  - BACKGROUND: Affective disorders typically have a better outcome than
      schizophrenia, although recent evidence suggests that some patients with
      affective disorder have a relatively poor outcome, with cognitive impairments and
      persistent symptomatology. METHOD: Fifty chronically hospitalised geriatric
      patients with mood disorders (major depression or bipolar disorder) were compared
      on the clinical symptoms and aspects of cognitive impairment with 308 geriatric
      schizophrenic patients who were hospitalised at the same institution. The two
      samples did not differ in current age or in premorbid education level, but the
      affective patients had a later age of onset and more females in the sample.
      RESULTS: There were no overall differences in cognitive functioning between the
      groups, although the clinical symptom profiles resembled those seen in better
      outcome patients. CONCLUSIONS: Cognitive impairment is present in poor-outcome
      patients with affective disorders as well as schizophrenia, suggesting that
      cognitive impairments predict poor outcome across psychiatric disorders and not
      just in schizophrenia.

PMID- 9246258
TI  - Epidemiology of psychiatric disorders in elderly compared with younger adults
      with learning disabilities.
AB  - BACKGROUND: The literature regarding psychiatric illness among elderly people
      with learning disabilities is limited and conflicting because of methodological
      differences. There have been no recent studies comparing psychiatric epidemiology
      between younger and older adults with learning disabilities, using the same
      methodology and definitions. METHOD: Comprehensive psychiatric examination using
      a semi-structured rating scale was undertaken on everyone with learning
      disabilities, aged 65 years or over (n = 134), living in a defined geographical
      area. Comparison was made with a randomly selected control group of adults with
      learning disabilities aged 20-65 years (n = 73) drawn from the same geographical
      area. RESULTS: Elderly people with learning disabilities have a greater
      prevalence of psychiatric morbidity than younger controls (68.7 v. 47.9%). Rates
      for depression and anxiety disorders are high, and dementia is common: there are
      equal rates for schizophrenia/delusional disorders, autism and behaviour
      disorders in the two groups. CONCLUSIONS: The higher psychiatric morbidity among
      elderly (compared with younger) people with learning disabilities has not
      previously received adequate recognition. This warrants further investigation by
      service planners and clinicians.

PMID- 9246259
TI  - Delusion, the overvalued idea and religious beliefs: a comparative analysis of
      their characteristics.
AB  - BACKGROUND: The study sought to investigate the form of the delusion in
      schizophrenia and the overvalued idea in anorexia, employing a range of belief
      characteristics to discover whether differences could be detected between them,
      and how they stood in general relationship to the religious beliefs of normals.
      METHOD: A belief rating scale was devised with 12 characteristics, and completed
      by 20 schizophrenics, 20 anorectics, and 20 normal controls. Comparisons were
      drawn between populations using the Mann-Whitney test, and different types of
      belief were contrasted within diagnostic groups using each subject as their own
      control by repeated-measures MANOVA. RESULTS: The schizophrenic delusion was
      differentiated from the overvalued idea in anorexia by a number of variables,
      which also served to distinguish both phenomena from religious beliefs held by
      normals. The schizophrenic delusion exhibited many of the qualities of an initial
      (or observational) belief, when its content suggested that it should manifest
      those of a derived belief. The anorectic overvalued idea, although occasionally
      an initial belief in terms of its content, was typically held in the form of a
      derived belief. CONCLUSIONS: A wider range of characteristics is required to
      define all the differences between delusion and the overvalued idea, and these
      have implications for belief modification programmes.

PMID- 9246260
TI  - Antipsychotic drug-induced dysphoria.

PMID- 9246261
TI  - Suicide in China.

PMID- 9246262
TI  - Mass hysteria.

PMID- 9246263
TI  - Recovered memories.

PMID- 9246264
TI  - Cognitive impairment associated with lamotrigine.

PMID- 9246265
TI  - Paroxetine discontinuation syndrome in association with sertindole therapy.

PMID- 9246266
TI  - Schizophrenia in Trinidad.

PMID- 9246267
TI  - Hospital-based primary care centres in ophthalmology.

PMID- 9246268
TI  - Medical cardiovascular treatment trials: relevant to medical ophthalmology in
      1997?

PMID- 9246269
TI  - The ocular presentation of neurofibromatosis 2.
AB  - Neurofibromatosis 2 (NF2) is an inherited disorder characterised primarily by
      bilateral vestibular schwannomas and other central nervous system tumours.
      Individuals with NF2 also have early onset cortical and posterior subcapsular or
      capsular cataract and other ocular abnormalities, such as retinal hamartomas.
      Although their diagnostic significance is rarely appreciated, the ocular
      manifestations are often the first sign of disease. We describe 5 cases that
      illustrate the diverse ocular manifestations of NF2.

PMID- 9246270
TI  - Oculopalatal myoclonus: eye movement studies, MRI findings and the difficulty of
      treatment.
AB  - Two cases of oculopalatal myoclonus with bilateral horizontal gaze palsies are
      presented. The abnormal vertical eye movements developed several months after
      brain stem haemorrhage. Eye movement measurements showed rhythmical vertical eye
      movements at similar rates (2.3 Hz and 2.4 Hz), unaffected by attempts to fixate,
      converge or gaze in any direction. T2-weighted MRI scans showed bilateral
      enlargement of the inferior olivary nuclei in both cases, which confirms the
      expected pathology previously demonstrated on autopsy. Both patients had severe
      oscillopsia and an attempt was made to improve this by bilateral disinsertion of
      the vertical rectus muscles. The pendular eye movements continued but were
      greatly reduced, in one case enough to relieve the oscillopsia. However, after 6
      months retrobulbar botulinum toxin was required to continue to provide relief
      from the oscillopsia. Other treatment options, including pharmacological agents,
      are discussed.

PMID- 9246272
TI  - Detached superior rectus following scleral buckling: anatomy and surgical
      management.
AB  - We describe two patients who developed vertical diplopia following
      circumferential scleral buckling for retinal detachments. Both were found to have
      hypodeviation and impaired elevation of the operated eye. In each case this was
      initially ascribed to the presence of the buckle itself, but there was no
      clinical improvement when this was subsequently removed, and the insertion of the
      superior rectus was therefore explored. In both patients this muscle was found to
      be detached from its normal insertion, and was identified in a retracted position
      overlying the insertion of the superior oblique. Following surgical re-attachment
      of the superior rectus, ocular elevation was restored, with resolution of
      symptoms.

PMID- 9246271
TI  - Left atrial myxoma causing ophthalmic artery occlusion.
AB  - A 45-year-old Caucasian woman presented with sudden onset right-sided
      hemiparesis, aphasia and a painful left eye. Examination revealed a bone-white
      fundus with no perfusion of either the retinal or choroidal circulations.
      Magnetic resonance imaging showed increased signal density of the left optic
      nerve sheath, orbital fat and extraocular muscles consistent with infarction of
      the ophthalmic artery distribution. An echocardiogram disclosed a mobile,
      multilobulated mass attached to the septal wall of the left atrium. Pathological
      examination of the resected tumour confirmed the diagnosis of endocardial myxoma.
      A colour Doppler study performed 1 month after surgery demonstrated absence of
      flow in the left ophthalmic artery. At 2 months, the left eye had no light
      perception and an intraocular pressure of 2 mmHg. This clinicopathological report
      describes the rare presentation of an acute ophthalmic artery obstruction
      secondary to atrial myxoma.

PMID- 9246273
TI  - Management of viral retinitis-associated retinal detachment in AIDS.
AB  - We retrospectively reviewed the results of surgery in 27 cases of retinal
      detachment related to viral necrotising retinitis in acquired immune deficiency
      syndrome (AIDS). Vitrectomy and silicone oil tamponade were performed in all
      cases. Scleral buckling was applied to 9 eyes. Silicone oil was left in the eye
      in all cases. Mean follow-up period was 13 weeks. Post-operative flattening of
      the retina at the posterior pole was achieved in 89% of the eyes. Anatomical
      results were not related to the intraoperative use of an encircling procedure.
      Visual acuity improved by 2 Snellen lines or more in 40% of cases and 67% of the
      eyes retained a post-operative ambulatory vision. Phacosclerosis and optic
      atrophy developed in 29% and 22% of cases, respectively. Vitrectomy and silicone
      oil tamponade without scleral buckling are effective in the management of
      retinitis-associated retinal detachments. This procedure is short and can be
      performed under local anaesthesia.

PMID- 9246274
TI  - Removal of lens fragments from the vitreous cavity.
AB  - Between March 1993 and September 1994 we treated 25 cases of lenses in the
      vitreous cavity. Nineteen of the 25 were the result of dislocation during
      phacoemulsification. During this time, we adopted a single surgical algorithm
      involving vitrectomy, heavy liquids and ultrasound fragmentation. The aims of
      this retrospective study were to test the validity of our surgical algorithm and
      to report on outcomes and complications. The indications for vitreous surgery
      were raised intraocular pressure, uveitis and poor vision. Vitreous surgery was
      carried out at a mean of 29 days following phacoemulsification. Six patients
      required heavy liquids and 5 needed ultrasound fragmentation. Vitreous surgery
      undertaken less than 17 days after phacoemulsification had an increased
      likelihood of requiring heavy liquids and/or fragmentation (p < 0.02). The
      greatest threat to a favourable visual outcome was retinal detachment, which was
      significantly associated with fragmentation and use of heavy liquids (p < 0.02).
      The presence of an intraocular lens (IOL) reduced the surgical options for
      removal of the lens fragments, and IOL should not be inserted where lens matter
      dislocates. The study suggests that we should avoid fragmentation and, provided
      the intraocular pressure and uveitis can be controlled, that vitreous surgery
      should be deferred for 2-3 weeks following phacoemulsification.

PMID- 9246275
TI  - Autogenous labial mucous membrane and banked scleral patch grafting for exposed
      retinal explants.
AB  - Following retinal detachment surgery, exposure of the scleral explant is uncommon
      and usually requires its removal. In patients with a history of multiple retinal
      detachment procedures or continuing vitreoretinal traction removal of an explant
      can lead to retinal redetachment. In such patients it is preferable to cover and
      retain an exposed explant rather than remove it. Various techniques have been
      described to cover exposed explants. If the exposed area is small a
      conjunctivoplasty or conjunctival graft is usually adequate. The use of banked
      scleral patch grafts has been described in the management of exposed orbital
      implants. We describe the use of this technique in combination with a labial
      mucous membrane graft in four patients with an exposed silicone retinal explant.
      With a minimum follow-up period of 11 months the explant remains covered in all
      patients.

PMID- 9246276
TI  - The effect of anaesthesia on the intraocular volume of the C3F8 gas bubble.
AB  - Long-acting intraocular gas bubbles are frequently used during vitrectomy to
      tamponade retinal breaks. The aim of this study was to determine the effect of
      nitrous oxide anaesthesia on the size and effectiveness of the post-vitrectomy
      gas bubble. Twenty vitrectomy procedures with injection of 12% perfluoropropane
      (C3F8) gas were performed. For 10 of the cases routine anaesthesia with nitrous
      oxide was used and for 10 cases non-nitrous anaesthesia with propofol was used.
      The volume of the intraocular gas bubble was estimated 24 hours post-operatively
      using A-scan biometry. At 24 hours the gas bubble occupied a mean of 65.1% of the
      eye in anaesthesia with nitrous oxide and a mean of 66.1% in anaesthesia with
      intravenous propofol. The wide range of values of gas-fill recorded at 24 hours
      makes comparison of the two groups inappropriate. Several factors may account for
      this spread of values, but in our opinion it is the uncontrolled leakage from the
      sclerostomies which is the most likely. This study suggests that anaesthesia
      using nitrous oxide does not adversely affect the size of the C3F8 gas bubble at
      24 hours post-vitrectomy when compared with anaesthesia without nitrous oxide.

PMID- 9246277
TI  - Sex hormone preparations and retinal vein occlusion.
AB  - Retinal vein occlusion (RVO) is most commonly seen in middle-aged or older
      patients and is associated with underlying cardiovascular risk factors. It is
      much less common in younger patients. Use of the oral contraceptive pill (OCP) is
      known to be a risk factor for cardiovascular and cerebrovascular disease. There
      have previously been a few isolated case reports of patients sustaining an RVO
      whilst taking the OCP. The aim of this study was to investigate patients
      sustaining an RVO whilst taking the OCP or hormone replacement therapy (HRT).
      From a large series of 588 patients, we found 11 with an RVO associated with sex
      hormone preparations. Of these, 6 had taken the OCP and 5 were HRT users. From
      this large group there were only 9 female patients aged under 35 years who
      sustained an RVO. Of these, 6 were associated with use of the OCP. All patients
      were investigated for recognised medical risk factors for RVO. None of these
      factors were identified in the patients who had used the OCP. Of the patients
      taking HRT, 4 of the 5 had other potential risk factors. From our large series,
      the prevalence of RVO in female patients under 35 years taking the OCP was 66%.
      There is a 30% uptake of the OCP in the general population. These data support
      the view that RVO is a contraindication to the use of the OCP. Additionally, it
      would appear (albeit from limited data) that patients who sustain RVO may
      continue with their HRT, as HRT is not a major single risk factor for RVO.

PMID- 9246279
TI  - Infiltrating inflammatory cell phenotypes and apoptosis in rejected human corneal
      allografts.
AB  - PURPOSE: The aim of this study was to survey the histopathological and
      immunohistochemical features of rejected human corneal allografts. METHODS:
      Following graft failure in each case due to rejection, paraffin-embedded
      specimens of 17 corneal transplants which had been replaced were examined by
      light microscopy and immunohistochemistry. Specimens were either first (n = 9),
      second (n = 4) or third (n = 4) grafts and were removed at varying intervals from
      4 weeks following documented rejection. RESULTS: Those grafts which were removed
      earliest following onset of rejection had the most intense graft inflammatory
      infiltrates. Immunohistochemical staining showed a high proportion of graft
      stroma-infiltrating cells expressing leucocyte common antigen, and many of these
      cells also bore T cell or macrophage markers. Leucocyte-keratocyte apposition and
      regional loss of keratocytes were observed in all rejection specimens, but not in
      non-rejected control grafts. In situ end-labelling of DNA double-strand breaks
      and morphological features identified keratocyte apoptosis in 5 of 12 specimens
      examined for this phenomenon. Corneal endothelial cells were absent in 7
      specimens and present in reduced numbers in the remaining 10 specimens.
      CONCLUSIONS: Endothelial cell monolayer attenuation and keratocyte loss are
      consistent findings in grafts removed subsequent to clinically observed
      endothelial rejection. Death of donor corneal cells is mediated, at least in
      part, by apoptosis. The stromal inflammatory infiltrate consists mainly of T
      lymphocytes and macrophages, which may be responsible for induction of keratocyte
      apoptosis.

PMID- 9246278
TI  - Macular corneal dystrophy type II: multiple studies on a cornea with low levels
      of sulphated keratan sulphate.
AB  - We investigated an individual macular corneal dystrophy (MCD) type II cornea from
      a 42-year-old woman with markedly reduced antigenic keratan sulphate levels. A
      characteristic 4.6 A X-ray reflection was evident, and the mid-stroma contained
      30% less sulphur than normal. Close packing of collagen was restricted to the
      superficial stroma. Abnormally large proteoglycan filaments were noted throughout
      the extracellular matrix and Descemet's membrane's posterior non-banded zone, but
      not its anterior banded zone. Small, collagen-associated stromal proteoglycans
      were susceptible to digestion with chondroitinase ABC, but not keratanase I or N
      glycanase. On occasion, collagen fibrils ranged in size from 20 nm to 58 nm, with
      preferential diameters of 34 nm and 42 nm. Corneal guttae were evident, as were
      numerous endothelial inclusions, most probably due to intracellular
      fibrillogranular vacuoles similar to those found in the stroma. The endothelium
      expressed reduced anti-keratan sulphate labelling.

PMID- 9246280
TI  - Topical cyclosporin A 2% in the treatment of vernal keratoconjunctivitis.
AB  - Topical cyclosporin A at a 2% concentration was used for 6 months in the
      management of 2 patients with vernal keratoconjunctivitis who had failed to
      respond to conventional therapy. We used one drop every 6 hours in both eyes
      during the first month and every 12 hours during the remaining 5 months. Clinical
      controls were carried out weekly during the first month, monthly during the 6
      month period and every 2 months thereafter. Cyclosporin A blood levels and serum
      creatinine were regularly monitored in both patients. Within the first month,
      both the symptoms and signs of the condition, in particular papillary
      proliferations, improved significantly and these results were maintained
      throughout the entire period of treatment and during 2 years of follow-up with
      conservative management (artificial tears).

PMID- 9246282
TI  - Astigmatism decay immediately following suture removal.
AB  - In a prospective study of 34 patients with high post-operative astigmatism (mean
      6.90 D, range 2.75-15.00 D) following extracapsular cataract surgery (13 limbal
      sections and 21 corneal sections), we used keratometry to assess the changes in
      corneal curvature seen within 30 minutes of suture removal and compared these
      with the astigmatism found 2 weeks later. The greatest change occurred within the
      first 5 minutes of suture removal (mean 3.63 D; 95% confidence interval (95% CI)
      2.85-4.41). The rate of decay then declined so that between 15 and 30 minutes the
      mean change was 0.56 D (95% CI 0.43-0.69). At 2 weeks a further mean decay of
      1.29 D (95% CI 0.99-1.61) occurred. Of the 6 patients exhibiting a residual
      astigmatism greater than 3.00 D at 30 minutes, 4 continued to do so 2 weeks
      later. Our study suggests that keratometry 30 minutes following suture removal is
      only moderately different from that seen 2 weeks later. Although not stable
      enough to suggest that patients could be routinely refracted within 30 minutes of
      suture removal, in cases where early visual recovery is essential, such as in
      monocular patients, it may be reasonable to offer a temporary spectacle
      correction immediately following suture removal. Furthermore keratometry at 30
      minutes after suture removal accurately predicts the necessity for further
      removal of sutures and indicates which patients can be discharged to the care of
      their own optometrist, making a further hospital visit unnecessary.

PMID- 9246281
TI  - The effectiveness of topical diclofenac in relieving discomfort following
      traumatic corneal abrasions.
AB  - Diclofenac is a non-steroidal anti-inflammatory drug available in an ophthalmic
      preparation. We present a prospective randomised double-masked placebo-controlled
      trial involving 40 patients that assessed the effectiveness of topical diclofenac
      in relieving pain from traumatic corneal abrasions. Statistical analysis of
      visual analogue and categorical pain scores revealed a significant reduction in
      pain experienced by subjects in the diclofenac group (p < 0.02).

PMID- 9246283
TI  - Post-operative iris prolapse following phacoemulsification and extracapsular
      cataract surgery.
AB  - PURPOSE: This study retrospectively compared and contrasted iris prolapse
      occurring following extracapsular cataract extraction and phacoemulsification.
      METHODS: The clinical notes of all patients who had undergone iris prolapse
      repair in the last 5 years at Southampton Eye Unit were recalled. Sixty-five
      patients (mean age 73 years; 41.6% male, 58.4% female) were identified out of a
      total of 7252 cataract operations performed (5983 extracapsular, 1269
      phacoemulsification). RESULTS: Fifty-nine (93.3%) iris prolapses occurred
      following extracapsular surgery (83% had corneal incisions, 17% limbal). We
      identified 3 cases of phaco-related prolapse each of which occurred where the
      scleral tunnel had been extended to enable insertion of a 7.0 mm optic
      intraocular lens but had not been sutured. Overall, the average best corrected
      visual acuity achieved was 6/9. CONCLUSION: The authors conclude that although
      iris prolapse is much less common following phacoemulsification, all scleral
      sections that are extended should be sutured.

PMID- 9246284
TI  - The outcome of 2.3 mm incision combined phacoemulsification, trabeculectomy and
      lens implantation of non-foldable intraocular lenses.
AB  - We report the results of 100 eyes in 88 patients that underwent combined
      phacoemulsification and implantation of non-foldable intraocular lenses (IOLs)
      following enlargement of the initial 2.3 mm opening and trabeculectomy.
      Intraocular pressure (IOP) control (< 21 mmHg) was attained in 96% of the eyes.
      Visual acuity of 6/12 or better was attained in 76% of the eyes. A filtering bleb
      was absent in only 11% of the eyes. All these outcomes were favourable compared
      with previously reported series in which foldable IOLs were inserted without
      enlargement of the initial trabeculectomy openings. We conclude that the
      combination of small-incision cataract surgery and trabeculectomy with
      implantation of non-foldable IOLs is a successful surgical approach for visual
      rehabilitation and glaucoma control in patients with concurrent cataract and
      glaucoma.

PMID- 9246285
TI  - The prevalence of cataract in two villages of northern Pakistan with different
      levels of ultraviolet radiation.
AB  - To study the effect of ultraviolet (UV) light on the development of age-related
      cataract, a community-based cross-sectional study was undertaken in two villages
      in the mountainous Northern Areas of Pakistan. The relative UV light exposure was
      calculated by the UK Universities Global Atmospheric Modelling Program using the
      variables direct sunlight hours per day, latitude and ground reflectivity. A
      total of 797 subjects (410 men, 387 women) over the age of 40 years from both
      villages were examined for the presence of cataract. The prevalence of cataract
      increased with age (p < 0.001) and was significantly higher in women at all ages
      (p < 0.01). There was no significant difference in the overall prevalence of
      cataract between the two villages. The male population in each village was
      subdivided into those who worked predominantly indoors and those who worked
      predominantly outdoors. All women worked outdoors. There was no significant
      difference in the prevalence of cataract between the male outdoor workers in the
      two villages. The indoor workers in the village with higher UV light exposure
      (Hunza) had a significantly higher cataract prevalence (p < 0.001) than the
      indoor workers in the village with lower UV light exposure (Nomol). In the
      village with lower UV light exposure (Nomol), the male outdoor workers had a
      significantly higher prevalence of cataract than the male indoor workers (p <
      0.001). There was no significant difference in the prevalence of cataract between
      the male indoor and outdoor workers in the village with higher UV light exposure
      (Hunza). Overall, these results are not strongly supportive of UV light being of
      major importance in cataractogenesis, but they are consistent with a saturation
      model of UV light as a risk factor for cataract formation.

PMID- 9246286
TI  - Electroretinographic findings in Fuchs' heterochromic cyclitis.
AB  - PURPOSE: Fuchs' heterochromic cyclitis (FHC) is an inflammatory disease of
      unknown aetiology. Although anterior segment signs and vitreous changes are well
      recognised, retinal features are unusual. To assess the extent of retinal
      involvement, we performed electrophysiological testing in a group of FHC
      patients. METHODS: Retinal function was assessed by means of flash
      electroretinogram (ERG) using a Ganzfeld stimulus, and pattern electroretinogram
      (PERG) using a checkerboard stimulus of spatial frequency 0.5 and 1.0 cycle per
      degree reversing at 6 Hz. A total of 21 patients with unilateral, normotensive
      FHC with visual acuities of 6/5 to 6/9 were studied. RESULTS: In the flash ERG,
      selective scotopic b-wave abnormalities occurred in 9 (43%) of 21 FHC eyes.
      Despite clear media and no history of ocular surgery, 7 patients showed
      abnormalities of the PERG. CONCLUSIONS: These electrophysiological findings
      suggest subclinical damage to the inner retinal layers, but not involving the
      photoreceptors, in eyes with FHC.

PMID- 9246287
TI  - The value of perioperative intraocular pressure measurement in trabeculectomy as
      a predictor of the early post-operative course.
AB  - PURPOSE: The purpose of the study was to assess the value of perioperative
      intraocular pressure (IOP) measurement in trabeculectomy as a predictor of
      drainage and related complications in the early post-operative period. METHODS: A
      prospective study was undertaken of 42 eyes (39 patients) followed up after
      trabeculectomy for the first post-operative month. RESULTS: Analysis of the
      change in IOP in the first post-operative month showed that at 1 month the
      pressure in all cases tended to similar values irrespective of the mean
      perioperative IOP. Early shallowing of the anterior chamber was, however,
      associated with a significantly lower perioperative IOP, although there was no
      significant difference in IOP at 1 month in these cases. CONCLUSIONS: The
      perioperative IOP appears to be effective in predicting anterior chamber
      shallowing in the first post-operative month with good sensitivity and
      specificity, but has little value as a predictor of the IOP at 1 month.

PMID- 9246288
TI  - Primary open angle glaucoma and hypothyroidism: chance or true association?
AB  - The prevalence of hypothyroidism in British patients with primary open angle
      glaucoma (POAG) was examined. A recently reported study from Montreal had shown a
      significant increase (p < 0.004) in biochemical hypothyroidism (23.4%) in a
      population of 64 POAG patients compared with controls (4.7%). Mechanisms for a
      possible causal association between the two diseases are discussed, including
      mucopolysaccharide deposition in the trabecular meshwork and vasculopathy
      altering ocular bloodflow. Reports of improved glaucoma control following
      treatment of hypothyroidism are discussed. This study examined 100 consecutive
      patients with POAG in a specialist glaucoma clinic. All patients were questioned
      regarding symptoms of thyroid dysfunction and previous thyroid disease. All
      patients not already taking thyroxine underwent an assay of thyroid stimulating
      hormone. The 4% (95% CI 1.1-9.4%) prevalence of overt hypothyroidism in our study
      shows no clinically significant increase either over controls in the Montreal
      study or over our local population. We conclude that in our local population
      there is no evidence for a clinically important association of hypothyroidism
      with glaucoma.

PMID- 9246289
TI  - Acute proptosis in relation to activated protein C resistance: a case report.
AB  - Activated Protein C resistance is a recently described clotting disorder,
      accounting for several previously undiagnosed thrombophilic states. Initially
      this defect had been associated with leg vein thromboses, but it is now
      recognised that other vascular beds are also prone to clotting in this disorder.
      We report a case of acute proptosis in a patient with Activated Protein C
      resistance, due to cavernous sinus thrombosis.

PMID- 9246290
TI  - Correction of blepharoconjunctivitis-related upper eyelid entropion using the
      anterior lamellar reposition technique.
AB  - Upper eyelid entropion is a complication of chronic blepharoconjunctivitis which
      may be easily missed unless careful examination of the lid margin of patients
      with trichiasis is carried out. Many patients undergo years of unsuccessful
      treatment for trichiasis because the underlying upper eyelid entropion has not
      been detected. We would like to recommend the already established procedure of
      anterior lamellar repositioning as a more permanent solution to this distressing
      condition and present the results of this procedure on 19 consecutive patients
      (28 lids). Our surgical technique is described and the results in this group of
      patients reported. The procedure was successful in 24 of 28 eyelids (85%), with
      success being defined as complete resolution of symptoms for a follow-up period
      of at least 10 months. Anterior lamellar repositioning is easy and relatively
      quick to perform and provides good functional and cosmetic results.

PMID- 9246291
TI  - A cautionary tale: Terson's syndrome presenting to eye casualty.

PMID- 9246292
TI  - Bilateral spontaneously regressed retinoblastoma with preservation of vision.

PMID- 9246293
TI  - Temperature-dependent resistance to gentamicin in graft keratitis by
      Stenotrophomonas (Xanthamonas) maltophilia.

PMID- 9246294
TI  - Long-term oral corticosteroids and osteoporosis prevention in an ophthalmology
      clinic.

PMID- 9246295
TI  - Transposition of homonymous hemianopia after craniopharyngioma surgery.

PMID- 9246296
TI  - Neisseria gonorrhoeae: a previously unreported cause of pre-septal cellulitis.

PMID- 9246297
TI  - Paediatric ophthalmology in West Mostar, Bosnia.

PMID- 9246298
TI  - Psychogenic erectile dysfunction complicating ophthalmic surgery.

PMID- 9246299
TI  - Valsalva retinopathy in pregnancy.

PMID- 9246300
TI  - Orbital tuberculosis.

PMID- 9246301
TI  - Traumatic retinal angiopathy and seat belts: pathogenesis of whiplash injury.

PMID- 9246302
TI  - Long-term follow-up of a single continuous adjustable suture in penetrating
      keratoplasty.

PMID- 9246303
TI  - Pre-operative assessment and investigation of ophthalmic patients.

PMID- 9246304
TI  - Pre-operative assessment and investigation of ophthalmic patients.

PMID- 9246305
TI  - [Pediatric hospitals in Bordeaux: three centuries of history].

PMID- 9246306
TI  - [Acute decompensations of bronchopulmonary dysplasia: management and prevention].

PMID- 9246307
TI  - [Anti-infective treatment of acute pneumopathies in children].

PMID- 9246308
TI  - [Conflicting therapeutic aspects during acute bronchiolitis in infants].

PMID- 9246309
TI  - [Usefulness of bronchodilator agents in infants under the age of 2 years].

PMID- 9246310
TI  - [Biological exploration of phosphorus calcium metabolism in children].

PMID- 9246311
TI  - [Pseudohypoparathyroidism: new diagnostic and therapeutic approaches].

PMID- 9246312
TI  - [Current treatment of renal osteodystrophy in children].

PMID- 9246313
TI  - [Contribution of osteo-densitometry in Turner syndrome and in somatotropin
      deficiencies].

PMID- 9246314
TI  - [Molecular mechanisms of familial rachitis].

PMID- 9246315
TI  - [Hox genes and genetic control of limb development].

PMID- 9246316
TI  - [Fibroblast growth factor receptors and hereditary abnormalities of bone growth].

PMID- 9246317
TI  - [Sex determination and differentiation in man: from pathology to genes].

PMID- 9246318
TI  - [Proteins in bone morphogenesis (BMP)].

PMID- 9246319
TI  - [Parental genomic imprinting and its implications in growth].

PMID- 9246320
TI  - [Nutritional requirements for pregnant women].

PMID- 9246321
TI  - [Fatty acids, fetal growth and pregnancy].

PMID- 9246322
TI  - [Prenatal stress during pregnancy and metabolic consequences in adult rats].

PMID- 9246323
TI  - [Diet and pregnancy: practical aspects].

PMID- 9246324
TI  - Dysphagia, dysarthria and falls in an elderly man.

PMID- 9246325
TI  - An unusual pulmonary mass.

PMID- 9246326
TI  - Abdominal mass in a 19-year-old with neurofibromatosis.

PMID- 9246327
TI  - Gingivitis, facial weakness and focal seizures.

PMID- 9246329
TI  - A retrocardiac shadow in an immunocompromised patient.

PMID- 9246328
TI  - Fever and a rash.

PMID- 9246330
TI  - Small bowel obstruction in an adult.

PMID- 9246331
TI  - Thyrotoxicosis and antithyroid drugs.

PMID- 9246332
TI  - Facial flushes and diarrhoea.

PMID- 9246333
TI  - Chest X-ray mass.

PMID- 9246334
TI  - Multiple bony swellings and joint stiffness.

PMID- 9246335
TI  - Rapid neurological deterioration in a 22-year-old man.

PMID- 9246336
TI  - Mental Dullness after thrombolytic therapy.

PMID- 9246337
TI  - Ectopic acromegaly.

PMID- 9246338
TI  - Acute abdomen after total hip replacement.

PMID- 9246339
TI  - An intra-abdominal tumour.

PMID- 9246340
TI  - Ring-enhancing lesions on computed tomography.

PMID- 9246341
TI  - Headache, vomiting and diplopia.

PMID- 9246342
TI  - An acutely painful leg.

PMID- 9246343
TI  - Proteinuria in a young man.

PMID- 9246344
TI  - An unusual late complication of gastric surgery.

PMID- 9246345
TI  - High fever and high lipids.

PMID- 9246346
TI  - Recurrent dehydration in a young girl.

PMID- 9246347
TI  - Excess adipose and heartburn.

PMID- 9246348
TI  - Pelvic mass in 46-year old man.

PMID- 9246349
TI  - Hypothyroidism presenting as acute abdomen.

PMID- 9246350
TI  - Skin lesions in a patient with hairy cell leukaemia.

PMID- 9246352
TI  - Dementia in a diabetic man.

PMID- 9246351
TI  - Bacteraemia and intestinal obstruction in a 74-year-old man.

PMID- 9246353
TI  - Quadriplegia with cervical cord compression.

PMID- 9246354
TI  - Fever and 'negative' blood cultures in an elderly woman.

PMID- 9246355
TI  - Phospholipase D: regulation by GTPases and protein kinase C and physiological
      relevance.

PMID- 9246356
TI  - Short-term regulation of acetyl CoA carboxylase in tissues of higher animals.

PMID- 9246357
TI  - Structure analysis of fatty acids by gas chromatography--low resolution electron
      impact mass spectrometry of their 4,4-dimethyloxazoline derivatives--a review.

PMID- 9246358
TI  - Dietary fatty acids--the N-6/N-3 balance and chronic elderly diseases. Excess
      linoleic acid and relative N-3 deficiency syndrome seen in Japan.

PMID- 9246359
TI  - [Pharmacological and chemical evaluation of stachytarpheta jamaicensis
      (Verbenaceae)].
AB  - After intraperitoneal administration of gradual aqueous doses obtained from
      Stachytarpheta jamaicensis leaves, the following effects were observed in rats: a
      reduction of motor activity and the alarm reaction, ataxia, sedation, analgesia,
      anesthesia, ptosis, piloerection, head tremors and a significant reduction of
      body temperature of about 8.4 degrees C. Robichaud's sign was present, probably
      due to some muscular relaxation. There were appreciable changes on respiration,
      with increment on amplitudes and reduction on the frequency, followed by apnea
      and the death of the animals, probably due to asphysia. Iridoid ipolamiide and
      the phenylpropanoid glycoside, verbascoside, were identified from the same
      extracts. Both metabolites have been indicated with potential pharmaceuticals
      properties in accord with ethnobotanical value attributed to this plant.

PMID- 9246360
TI  - [Chemical and biological evaluation of the effect of plant extracts against
      Plasmodium berghei].
AB  - Extracts from thirteen species of plants were evaluated by "in vivo" antimalarial
      test against plasmodium berghei effects. Significant activities were observed in
      the ethyl acetate and aqueous extracts, elaborated of Cedrela tonduzii leaves,
      Trichilia havanensis and Trichilia americana barks, Neurolaena lobata and
      Gliricidia sepium leaves and Duranta repens fruits. Compounds identified include
      flavanoids, coumarins, mellilotic acid and iridoids which some kind of biodynamic
      activity has previously been reported. The flavone quercetin 1 purified from C.
      tonduzii gave strong antimalarial activity, however, its respective glucosides
      (quercetin 3-glucoside 2 y robinine 7) showed little significant activity.

PMID- 9246361
TI  - [Seasonality of parasites and intestinal bacteria in vegetables that are consumed
      raw in Costa Rica].
AB  - In Costa Rica, a total of 640 samples from eight different vegetables used for
      raw consumption, were analyzed for the presence of intestinal parasites and fecal
      coliforms. Eighty samples of each vegetable were analyzed, forty during the dry
      season and forty in the rainy. A greater, but unsignificant (p > 0.05) level of
      fecal coliforms was found during the dry season. Levels of Escherichia coli, were
      higher (p < 0.05) during the dry season in lettuce (Latuca sativa) and cilantro
      (Coleandrum sativum) leaves. Cysts of Endolimax nana, Entamoeba coli, Entamoeba
      histolytica, Giardia intestinalis and Cryptosporidium sp. were found in all
      vegetables. The greater percentage of positive samples was found during the dry
      season, although these relation was only corroborated (p < 0.05) in radish
      (Raphanus sativus) and cilantro leaves. Only lettuce and cilantro levels showed a
      positive linear correlation (p < 0.05) between occurrences of intestinal
      parasites and fecal coliforms.

PMID- 9246362
TI  - Seroepidemiology of toxoplasmosis in humans: possible transmission routes in
      Costa Rica.
AB  - A serological survey with immunofluorescence techniques to detect toxoplasma
      antibodies was done on a sample of 1234 Costa Ricans. The overall prevalence was
      76%; it increased from 60% in donors aged 1-4 years to 90% in those over 25
      years. No significant difference was found in seropositivity between males
      (42.8%) and females (57.2%) and between donors from urban and rural (LPI) areas.
      Consumption of raw meat, especially prepared meat, was significantly correlated
      with antibody prevalence, but cat contact was not, indicating a possible change
      in the usual pattern of transmission described for the country. Nevertheless, our
      data suggest that infectious cat feces play an important role in the transmission
      of toxoplasmosis.

PMID- 9246363
TI  - [Transversal partitioning and interspecific associations in communities of
      ectoparasitic metazoans in marine sciaenid fishes from Peru].
AB  - During 1987 and 1988 marine sciaenid fishes from the central Peruvian coast were
      examined: 237 Menticirrhus ophicephalus, 124 Paralonchurus peruanus, 249 Sciaena
      deliciosa, 50 Sciaena fasciata and 311 Stellifer minor. Thirty metazoan
      ectoparasites were identified, 18 helminths and 12 crustaceans. Paralonchurus
      peruanus was the species with higher number of ectoparasite species (11). The
      communities of ectoparasites were dominated by diplectanid monogeneans. The
      following showed preference by some site of infestation in their transversal
      partitioning: Rhamnocercoides menticirrhi, Rhamnocercus spp., Diplectanum sp.,
      Pseudohaliotrema paralonchuri, Pedocotyle annakohni, P. bravoi, Caligus
      callaoensis and Lernanthropus huamani. With the exception of P. peruanus, these
      fishes showed an overall positive association in their ectoparasite communities.
      Menticirrhus ophicephalus and S. deliciosa had the most pairs of associated and
      covariated species. Paralonchurus peruanus and S. minor showed no interspecific
      associations. Negative interspecific association and covariation were not
      determined. The pair R. menticirrhi-L. huamani (in M. ophicephalus) had the
      highest association degree. These results suggest an absence of competitive
      interspecific processes.

PMID- 9246364
TI  - [Parasitological evidence on the phylogeny of hominids and cebids].
AB  - A systematic revision of the ectoparasites (lice) of the hominids and ceboids
      supports the Trogloditian hypothesis, according to which the genus Homo is the
      sister of Pan, and the genus Gorilla the sister group of both. The phylogenetic
      analysis of this matrix derived from the study of primate lice shows an C.I. of
      0.71 for the Trogloditian hypothesis including the ceboids in the analysis.

PMID- 9246365
TI  - The use of water chemistry and benthic diatom communities for qualification of a
      polluted tropical river in Costa Rica.
AB  - The water quality of several sections of a tropical river subjected to severe
      pollution was studied through physico-chemical water analysis and benthic diatom
      assemblages. The methodology follows the concept of differential species groups
      and that of its modification for the groups of nutrient-differentiating species
      for rivers rich in both oxygen and inorganic nutrients. The trophic indication of
      the latter authors correspond clearly with the results of chemical observations
      made in this study. The most abundant species found in this river were Navicula
      goeppertiana, Gomphonema parvulum, Gomphonema sp. aff. pumilum, Nitzschia palea,
      Nitzschia amphibia, Nitzschia clausii Nitzschia inconspicua, Navicula seminulum,
      Navicula sp. aff. cryptocephala, Navicula schroeterii var. escambia, Cymbella
      sinuata and Surirella sp. aff. roba. These species are known to be tolerant to
      organic pollution and eutrophication. Therefore we may conclude that diatoms are
      useful for biological monitoring of disturbed tropical rivers.

PMID- 9246366
TI  - [Nutrients in 39 Mexican coastal lagoons].
AB  - An analysis of 39 Mexican coastal lagoons most in tropical environments, shows no
      nutrient limitation for primary productivity: even minimum nutrient values are
      higher than those of similar systems (mostly of temperate zones). In some cases,
      nutrient variations are large and indicative of heterogeneity. The N:P ratio is
      more important than simple nutrient concentrations. Using this ratio, coastal
      lagoons are classified as limited in nitrogen (< 5) or phosphorus (> 10).

PMID- 9246367
TI  - [Regeneration of tree cover in a small urban forest reserve from the moist
      Premontane region].
AB  - The tropical premontane moist forest is one of the most destructed life zones in
      Costa Rica. For such regions, a small natural preserve system has been proposed.
      An inventory of trees greater than 3.5 cm in diameter at breast height was done
      in one hectare urban forest patch that was left under natural regeneration for 30
      years. The inventory included 940 individuals of at least 55 species and 32
      families. A Holdridge Complexity Index of 58 was obtained. There was a strong
      dominance by small-diameter trees of successional and exotic species.

PMID- 9246368
TI  - Vegetation-environment relationships based on a life-forms classification in a
      semiarid region of tropical Mexico.
AB  - Taking the view that morphological characteristics represent behavioral
      strategies of plants to cope with environmental pressures, we defined 18 life
      forms, using multivariate classification techniques in a tropical semiarid
      ecosystem in Central Mexico. A multiple discriminant analysis confirmed the
      existence of these groups. A null model of random membership of species to life
      forms was significantly different from our classification. Vegetation-environment
      relationships were examined with Detrended Canonical Correspondence Analysis
      (DCCA). Ordination axes were interpreted mainly be altitude and soil moisture.
      Response curves of life-forms along these gradients were explored fitting
      generalized linear models (GLIM's). We believe that the life-forms approach for
      the study of vegatation-environment relationships is a valid alternative to the
      traditional species approach usually used in physiological research because: i)
      life-forms number was found to be an excellent species diversity predictor, ii)
      this approach enables considerable reduction in the bulk of data without losing
      ecological information, and iii) life-forms represent ecological strategies per
      se and, they constitute an index of the number of different ways the desert's
      resources are utilized.

PMID- 9246369
TI  - Habitats and biodiversity of decapod crustaceans in the SE Gulf of California,
      Mexico.
AB  - Samples of benthic macro-fauna were obtained in different habitats along and off
      the coast of Southern Sinaloa, Gulf of California, Mexico, from 1978 to 1991.
      Occurrence of species of decapod crustaceans was registered for six habitats,
      from the interidal to depth of 1200 m. A total of 299 species were collected,
      belonging to 53 families and including 17 species of Penaeoidea, 45 of Caridea, 6
      of Thalassinidea, 5 of Palinura, 1 of Astacidea, 63 of Anomura, and 162 of
      Brachyura. Number of species varied considerably from one habitat to another.
      Highest biodiversity was observed in the Bay of Mazatlan, with 121 species,
      followed by the continental shelf and the rocky interidal (107 species each), the
      estuarine/coastal lagoons (48 species), the upper slope (18 species) and the
      sandy beaches (9 species). One species was found to be strictly insular
      terrestrial and two are primarily associated with the flotsam. The results of
      this survey were compared with distribution data available for decapod
      crustaceans fauna from the SE Gulf of California and the Eastern Tropical Pacific
      zoogeographic region (ETP). The fauna collected represents 82% of the species
      cited for the area for coastal and shallow subtidal habitats (to ca. 115 m depth)
      and 57.6% of deep water (> 200 m) species known to occur in the Gulf of
      California. Except in two cases, similarity indices (SI) based on the number of
      species common to any pair of habitats were all very low. Continental shelf and
      the Bay of Mazatlan have 57 species in common (SI = 0.50), while rocky shore
      habitat and the Bay of Mazatlan share 27 species (SI = 0.24). Comparative studies
      of decapod crustaceans communities for the ETP are almost lacking altogether.
      Available data, however, indicate that biodiversity observed on Southern Sinaloa
      is so far the highest on record for marine and brackish-water habitants for a
      given section of this tropical zoogeographic region.

PMID- 9246370
TI  - [Zooplankton of the Costa Rica Dome: taxonomy and biogeography].
AB  - A list of the species and taxa of some pelagic animals from a tropical upwelling
      region, based on collections made off the coast of Costa Rica is presented. The
      list includes a total of 224 species, 53 genera and 11 subspecific forms in
      Cnidaria, Annelida, Mollusca, Artropoda (Crustacea), Chaetognatha and Pisces.

PMID- 9246371
TI  - [Rearing crassostrea gigas (Bivalvia:Ostreidae) in a semi-rigid net].
AB  - A culture system, consisting of a semi-rigid net, with an ABS frame filled with
      styrofoam was used for the culture of the Pacific oyster Crassostrea gigas, from
      3.0 mm length seed. The culture system was tested in three locations, two inside
      San Quintin Bay and one in San Martin Island. The mean monthly growth was 8.69 mm
      and 8.96 mm in the Bay and 7.33 mm in San Martin Island. These growth rates show
      that this species can attain commercial sizes in 6 months, using the culture
      system tested.

PMID- 9246372
TI  - [The benthonic community as bioindicator of altered and recovering zones in
      Toledo creek (Uruguay)].
AB  - Macrozoobenthos composition and abundance of an organic polluted stream (A.
      Toledo, Uruguay) are compared among sites of control (C), degradation (D) and
      recuperation (R), which were seasonally sampled. Water ionic composition,
      conductivity, pH, temperature and COD were not different among sites, while
      oxygen, and BOD did show significant differences. Benthos was more abundant in R
      mainly due to Heleobia spp. Oligochaetes were dominant in C and D, with
      Branchiura sowerbyi only in C and Limnodrilus hoffmeisteri in D. Hirudinea,
      mainly Gloiobdella michaelseni, occurred almost only in R. the richness of taxa
      was higher in R, but its high abundance of Heleobia spp. and Sphaeridae leads to
      the lowest diversity, which was higher in C than D, and in warm than in cold
      seasons for these two sites. The logarithmic distribution model shows communities
      of low evenness in all sites.

PMID- 9246373
TI  - Depth related distribution of benthic macrofauna in a Costa Rican crater lake.
AB  - On two different opportunities the distribution and diversity of the benthic
      macrofauna was studied at different depths in the Laguna del Cerro Chato crater
      lake, Alajuela, Costa Rica. For both surveys, the deep samples had significantly
      lower species diversity and evenness than the shallow samples. There was a drop
      in species diversity and evenness at 6 m, followed by an increase at 9 m. This
      pattern is associated with fluctuations in the lake's thermocline. Chironomids
      were the most abundant organism in both surveys and the genus Chironomus
      dominated at all depths. Analysis of the elements Ca, Cu, S, N, Fe, P and
      percentage of organic matter in the bottom sediments did not show a clear
      bathymetrical distribution. However, at a depth of 9 m the increase in both N
      content and percentage or organic matter could be related to the increase in
      abundance of organisms.

PMID- 9246374
TI  - The neurochemistry of Alzheimer's disease.
AB  - This paper gives a review of the neurochemical alterations that characterize
      Alzheimer's disease. The quantitative distribution of each compound or group of
      compounds over the central nervous system and their concentrations in the
      cerebrospinal fluid as well as receptor interactions and densities are discussed.
      Where possible, these neurochemical alterations are correlated with cognitive and
      noncognitive symptoms. A degeneration of the cholinergic nucleus basalis of
      Meynert characterizes Alzheimer's disease and results in neocortical cholinergic
      deficits correlating with cognitive impairment. Catecholaminergic changes include
      prominent cell loss of the noradrenergic locus coeruleus leading to decreased
      norepinephrine concentrations in cerebrospinal fluid and several cortical and
      subcortical areas. Modest, but identical trends are reported for epinephrine and
      dopamine. The former alterations are correlated with depression and psychosis in
      Alzheimer's disease. The serotonergic nucleus raphe dorsalis shows evidence of
      degeneration, causing a decreased serotonin content of the neocortex and the
      cerebrospinal fluid, which is correlated with both cognitive and noncognitive
      symptomatology. Several-often less understood-changes of amino acids and
      neuropeptides will be reviewed. Finally, the neurochemical aspects of cytokine
      mediated inflammatory reactions and of oxidative stress in the physiopathology of
      Alzheimer's disease are reviewed.

PMID- 9246375
TI  - Adult neuronal ceroid-lipofuscinosis--personal observations.
AB  - A workshop on the diagnostic criteria of adult neuronal ceroid-lipofuscinosis
      (ANCL) or Kufs' disease represented an unique opportunity to make a critical
      review of the ANCL material from the files of the Born-Bunge Foundation. Our
      review included the clinical data when available, the light microscopic sections
      and the electron micrographs. When the postmortem material had not been
      immediately fixed in glutaraldehyde, we sampled formalin-fixed material, post
      fixed it and used classical electron microscopic techniques to better define the
      ultrastructure of the stored products. Only one family fulfilled the criteria for
      ANCL Neurons and vascular smooth muscle cells contained membrane-bound inclusions
      with curvilinear, rectilinear and fingerprint profiles.

PMID- 9246376
TI  - The relationship between sleep and cognitive functions during wakefulness: an
      introduction.

PMID- 9246377
TI  - Frontal lobe-related cognitive functions in patients with sleep apnea syndrome
      before and after treatment.
AB  - Impairments of cognitive executive functions has been previously suspected to
      occur in Sleep Apnea Syndrome (SAS), as suggested by some neuropsychological
      studies. However such functions have not been assessed directly. In the present
      study, ten patients with SAS were evaluated with various focused frontal lobe
      related tests in comparison with ten matched normal controls. Such tasks explored
      attention, short term memory spans, learning abilities, planning and programming
      capacities, categorizing activities and verbal fluency. Patients were found with
      a significant decreased ability to initiate new mental processes and to inhibit
      automatic ones in conjunction with a tendency for perseverative errors. They were
      also affected with deficits of verbal and visual learning abilities and they had
      reduced spans. Patients were submitted to continuous positive airway pressure
      (CPAP) and further reevaluated after 4-6 months of treatment. Patients were found
      to have normalized most of their cognitive executive and learning disabilities,
      except for all the short-term memory tests which remained unchanged. These
      findings are discussed in light of data from the literature concerning cognitive
      impairments described for patients with isolated daytime sleepiness versus
      hypoxemia, as illustrated in other pathological or physiological circumstances.
      The contribution of frontal lobe-related systems in short-term memory functions
      is also taken into account.

PMID- 9246378
TI  - Cognitive deficits in patients with daytime sleepiness.
AB  - A chief complaint of subjects with daytime sleepiness is the disturbance of
      cognitive functions like concentration, learning and memory. Since sleepiness
      interferes with the regulation of vigilance, one may assume that a disturbance of
      this basic dynamic variable causes deficiencies in information processing which
      in turn reduce the capacity for learning and memory. In two studies the time
      course of vigilance was measured by means of the critical flicker fusion (CFF)
      test in patients with narcolepsy or with an obstructive sleep apnea syndrome
      (OSAS). The CFF test was applied at 15 min intervals. The total test duration was
      ten hours in the study with narcoleptic patients and three hours in the study
      with OSAS patients. The mean level of performance was similar in healthy subjects
      and those with narcolepsy, while the latter displayed a three- to four-fold
      increase in temporal variability. Such an increase in variability of performance
      was not seen in subjects with OSAS. These data suggest that clinically
      distinguishable groups of patients with daytime sleepiness differ also in the
      pattern of performance impairment.

PMID- 9246379
TI  - Cognitive deficits in insomnia patients.
AB  - This study investigates performance in insomnia patients, comparing it with
      performance in normals matched not only on age and sex but also on education and
      occupation. There were 26 pairs of insomniacs and normals; and the computer
      driven performance battery, lasting about one hour, was administered three times
      over the course of a day. In addition, an auditory vigilance test was also
      administered twice. Insomniacs performed worse than normals on reaction time
      (they were both slower and more variable), they swayed more on the balance test,
      and they forgot more numbers on the Digit Span Test. There were no significant
      differences in Digit Symbol Substitution, Divided Attention, and Auditory Verbal
      Learning Tests, suggesting that the pattern of deficiencies in insomnia is
      different than that in sleep-deprived subjects. When insomniacs were administered
      the performance batteries after spontaneously occurring good or poor nights,
      little differences in performance were observed.

PMID- 9246380
TI  - Functional uncertainty, aging and memory processes during sleep.
AB  - Disorganized sleep patterns, can be found both during normal development and in
      pathological conditions. Aging could also be accompanied by a disorganization of
      the night sleep episode; sleep could be interrupted by spontaneous awakening,
      sleep cycle could be shortened or incomplete, sleep states modified. These
      patterns suggest an inability to sustain a stable condition, i.e. a condition of
      functional uncertainty. Biological and cognitive implications of functional
      uncertainty conditions are discussed. In particular, the hypothesis has been put
      forward that disturbances of sleep could have a detrimental role on memory.
      Recent results obtained in our lab support this hypothesis: recall is correlated
      with NREM-REM cycles proportion. Future research should ascertain the role of the
      functional uncertainty with respect to the kind of memory being involved during
      sleep, and establish how much and for which cognitive processes (including those
      involved in dream production) the inability to sustain a steady condition impairs
      the functioning during sleep. The duration of the functional uncertainty
      condition is also important. The long-term study of the link between functional
      uncertainty and cognitive resources, could be important for the understanding of
      the night life and for an adequate treatment of patients.

PMID- 9246381
TI  - Effects of benzodiazepines, sleep and sleep deprivation on vigilance and memory.
AB  - Anterograde amnesia is one of the troublesome adverse effects of the
      benzodiazepines, especially when they are used as tranquillizers. Interestingly,
      benzodiazepines also produce retrograde facilitation. In this review, a unifying
      hypothesis concerning both the cognitive enhancement and the cognitive decrement
      is discussed: the decrease in vigilance or sedative-hypnotic properties of the
      benzodiazepines induces a superficial type of encoding and consolidation. This is
      expressed in anterograde amnesia. The shallower encoding also causes less
      retrograde interference and retrograde facilitation is the result. In this way
      also the positive effect of sleep on memory is explained. In a series of
      experiments, this hypothesis was investigated. Anterograde amnesia and retrograde
      facilitation was demonstrated after benzodiazepine intake in healthy, volunteers.
      It was striking that amnestic effects and retrograde facilitation were most
      prominent when memory was tested one week after drug intake. A decrease in
      vigilance was also obtained by sleep deprivation and an increase by the gavage of
      the central stimulant methylphenidate. The latter vigilance increasing drug did
      not change memory aspects. Also memory effects were hardly present in sleep
      deprived subjects with low levels of vigilance and the performance on memory
      tests were not changed. This jeopardizes the vigilance hypothesis of the memory
      effects of the benzodiazepines. However, amnesia under the influence of
      benzodiazepines was less for semantic related words than for unrelated words.
      This suggests that information might be stored without appropriate contextual
      cues. Only under special circumstances this information can be retrieved. It is
      further speculated that this storage costs less efforts leading to less
      retrograde interference and consequently retrograde facilitation.

PMID- 9246382
TI  - Effect of bovine serum albumin on the calcium release channel of sarcoplasmic
      reticulum from rabbit skeletal muscle.
AB  - The effect of bovine serum albumin (BSA) on the activity of the calcium release
      channel of the sarcoplasmic reticulum from rabbit skeletal muscle was
      investigated using both tension recording from skinned fibres and
      electrophysiological recording of unitary channel currents from planar lipid
      membranes. BSA had no effect on the Ca2+ affinity of the contractile proteins,
      elicited no tension per se in Ca(2+)-loaded skinned fibres, but potentiated
      caffeine-induced tension. Maximum potentiation was observed with 0.05-0.5% BSA.
      BSA (0.1%) had no detectable effect on the basal activity of the Ca(2+)-release
      channel incorporated in lipid bilayer. However, channel stimulation elicited by
      either caffeine (2 mM) or ATP (60 microM) was further enhanced by BSA (0.1%), as
      indicated by significant increases in Po, the open probability of the channel.
      These results suggest that BSA can modulate the response of the skeletal muscle
      SR Ca(2+)-release channel to different activators such as caffeine and ATP.

PMID- 9246383
TI  - 5-Hydroxytryptamine, angiotensin and bradykinin transiently increase
      intracellular calcium concentrations and PKC-alpha activity, but do not induce
      mitogenesis in human vascular smooth muscle cells.
AB  - The potent vasoconstrictor substances, 5-hydroxytryptamine (5-HT), angiotensin II
      (A II), and bradykinin bind to G-protein coupled receptors and activate
      phospholipase C-beta. Using the Fura-2 technique and microfluorometry we found
      that all three agonists induce a transient increase in intracellular calcium
      ([Ca2+]i) by releasing stored calcium in human renal artery smooth muscle cells.
      Using binding of [3H]-phorbol dibutyrate (PDBu) to quantify membrane-associated
      protein kinase C (PKC) we also showed that 5-HT, A II and bradykinin induced a
      rapid but transient translocation of protein kinase C (PKC) to the plasma
      membrane. The time-course of the rise in [Ca2+]i was similar to that of the
      increase in [3H]-PDBu binding, suggesting transient activation of the calcium
      dependent alpha-isoform of PKC. Following prolonged pre-treatment with
      tetradecanoyl phorbol acetate (100 nmol L-1), which down-regulates PKC-alpha and
      delta, the angiotensin-induced PKC translocation was lost. 5-HT, A II or
      bradykinin were unable to increase cell proliferation or act as a co-mitogens
      with platelet-derived growth factor in human vascular smooth muscle cells. Thus,
      transient increases in [Ca2+]i or PKC activity by a vasoconstrictor agent are
      insufficient to cause vascular smooth muscle proliferation.

PMID- 9246384
TI  - Endothelium-dependent vascular smooth muscle relaxation activated by electrical
      field stimulation.
AB  - Electrical field stimulation (EFS) produced relaxation of contracted arteries in
      the presence of tetrodotoxin. In the present study the contributions of vascular
      smooth muscle repolarization and endothelial release of nitric oxide to the
      relaxation response were investigated using isolated rat tail arteries and bovine
      aortic endothelial cells (BAEC). Intact and endothelium-denuded rings or intact,
      pressurized artery segments were contracted with either phenylephrine or KCl
      prior to EFS. Electrical field stimulation induced a small relaxation in denuded,
      phenylephrine contracted rings that was inhibited by the K+ channel blockers
      glibenclamide and BaCl2. In intact, phenylephrine-contracted rings, EFS induced
      significantly larger relaxations that were inhibited by BaCl2 as well as by L
      NAME, an inhibitor of nitric oxide (NO) synthase, and methylene blue. EFS-induced
      relaxations were completely inhibited when BaCl2 and L-NAME or methylene blue
      were combined. Exposure to Ca(2+)-free buffer or diltiazem also inhibited the
      relaxation while ascorbic acid had no effect. Effluent from electrically
      stimulated BAEC caused denuded, phenylephrine contracted rings to relax. The
      ability of the effluent to cause relaxation was almost completely blocked by
      exposure of the BAEC to L-NAME or exposure of the recipient vascular smooth
      muscle to methylene blue; glibenclamide caused partial blockade. Simultaneous
      measurements of membrane potential and intraluminal pressure showed that EFS
      induced membrane repolarization preceded changes in steady-state pressure. It is
      concluded that (1) the smooth muscle cells possess an endothelium-independent
      repolarization mechanism, (2) EFS causes endothelial cells of intact arteries to
      release NO and possibly a hyperpolarizing factor, (3) EFS of BAEC causes release
      of NO, and (4) EFS-induced relaxation depends on vascular smooth muscle cell
      membrane repolarization and endothelial cell release of vasoactive substances.

PMID- 9246385
TI  - The energetics of the quiescent heart muscle: high potassium cardioplegic
      solution and the influence of calcium and hypoxia on the rat heart.
AB  - Heart basal metabolism has been classically studied as the energy expenditure of
      those processes unrelated to mechanical activity and often measured by rendering
      the heart inactive using cardioplegic solutions (usually by increasing
      extracellular K concentration ([Kle]). In arterially perfused rat heart (at 25
      degrees C), raising [K]e from 7 to 25 mM at a constant extracellular Ca
      concentration ([Ca]e) (0.5 mM), induced an increase in resting heat production
      (Hr) from 4.1 +/- 0.3 to 5.1 +/- 0.3 mol. wt g-1. Under 25 mM K additional
      increase in [Ca]e further increased Hr to 6.0 +/- 0.4, 7.0 +/- 0.4 and 8.3 +/-
      0.9 mol. wt g-1 for 1, 2 and 4 mM Ca, respectively. While under 7 mM K perfusion
      Hr was not affected by 4 microM verapamil, under 25 mM K and 2 mM Ca 0.4 microM
      verapamil induced a decrease in Hr (-1.6 +/- 0.2 mol. wt g-1, n = 5, P < 0.001).
      Caffeine increased Hr under 0.5 mM Ca and 7 mM K perfusion (+0.32 +/- 0.06 and
      +1.19 +/- 0.25 mol. wt g-1 for 1 and 5 mM caffeine respectively), but under 25 mM
      K conditions Hr was not affected by caffeine 2 mM. Severe hypoxia decreased Hr
      under both 7 and 25 mM K (3.7 +/- 0.5 to 2.7 +/- 0.4 mol. wt g-1 and 7.0 +/- 0.4
      to 2.2 +/- 0.5 mol. wt g-1, respectively) suggesting that the increased Hr
      associated with the verapamil sensitive fraction of heat released is associated
      to a mitochondrial mechanism. Therefore, the use of high [K]e overestimates basal
      values by increasing a verapamil sensitive fraction of the energy released. In
      addition, high [K]e modifies a caffeine sensitive energy component probably due
      to a depletion of caffeine-dependent Ca stores.

PMID- 9246386
TI  - Heart rate variability in healthy subjects is related to age and gender.
AB  - The effects of age and gender on heart rate variability as measured by spectral
      and time domain analysis of 24 h ECG recordings were evaluated in 101 healthy
      subjects, 49 men and 52 women (20-69 years of age). In the frequency domain,
      total power, very low-frequency power, low-frequency power and high-frequency
      power were negatively correlated to age (P < 0.001 for all variables). Total
      power decreased by 30% between 20-29 and 60-69 years of age. In the time domain,
      SDNN-index, the mean of the standard deviations of all normal R-R intervals for
      all 5 min segments of a 24 h ECG recording, was negatively correlated to age (P <
      0.001). Total power, very low-frequency power, low-frequency power and the low
      frequency/high-frequency ratio were lower in women (P < 0.05, P < 0.05, P < 0.01
      and P < 0.01), although the absolute differences were much smaller than for age.
      There was a pronounced circadian variation; at night total power increased in all
      age groups (P < 0.01). The results show that age, and to a lesser degree gender,
      are important determinants of heart rate variability in healthy subjects. Heart
      rate variability is a valuable tool for risk stratification in cardiovascular
      disease, but the physiological effects of ageing, with diminishing heart rate
      variability in older age groups, must also be taken into account.

PMID- 9246387
TI  - Capillary geometry in the soleus muscle of rats cold-acclimatized for 68
      generations.
AB  - The effects of chronic cold exposure on soleus muscle capillarity were examined,
      particularly in terms of the distribution of arteriolar and venular capillaries
      and their capillary domain area (CDA) in adult rats exposed to cold for 68
      generations (CG; n = 6). These parameters were compared with those obtained from
      control rats (CON; n = 5) and deacclimatized rats (DCG; n = 4), reared in
      thermoneutral temperature after being reared for 11 generations in cold.
      Morphometric data were obtained from muscle cross sections exposed to a double
      staining method that stained the arteriolar and venular portions of capillaries
      blue and red, respectively. In CG, the capillary densities of arteriolar and
      venular capillaries were significantly greater than that of both CON and DCG (P <
      0.05). The CDA of arteriolar, intermediate and venular portions in CG was
      significantly smaller by 15, 14 and 13%, respectively, than those of respective
      portions in CON (P < 0.05). Although CDA of arteriolar and venular capillary
      portions was also smaller in DCG than in CON, the degree of reduction was less in
      DCG than in CG. The succinate dehydrogenase activity of soleus muscle was
      significantly greater in CG than in both CON and DCG (P < 0.05). These results
      suggest that adaptive changes in the oxygen transport system, identified as an
      increase in the number of arteriolar capillaries and a reduction in the diffusion
      distance for oxygen, were observed in the soleus muscle after chronic cold
      exposure. These changes may improve the effective oxygen supply to muscle tissues
      and enable muscle tissues to promote thermogenesis in the cold atmosphere.

PMID- 9246388
TI  - Middle cerebral artery blood velocity during rowing.
AB  - Dynamic exercise increases the transcranial Doppler determined mean blood
      velocity in basal cerebral arteries corresponding to the cortical representation
      of the active limb(s) and independent of the concomitant rise in the mean
      arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood
      velocity response to ergometer rowing when regulation of the cerebral perfusion
      is challenged by stroke synchronous fluctuation in arterial pressure. Rowing
      increased mean cerebral blood velocity (57 +/- 3 to 67 +/- 5 cm s-1; mean +/- SE)
      and mean arterial (86 +/- 6 to 97 +/- 6 mmHg) and central venous pressures (0 +/-
      2 to 8 +/- 2 mmHg; P < 0.05). The force on the oar triggered an averaging
      procedure that demonstrated stroke synchronous sinusoidal oscillations in the
      cerebral velocity with a 12 +/- 2% amplitude upon the average exercise value.
      During the catch phase of the stroke, the mean velocity increased to a peak of 88
      +/- 7 cm s-1 and it was in phase with the highest mean arterial pressure (125 +/-
      14 mmHg), while the central venous pressure was highest after the stroke (20 +/-
      3 mmHg). The results suggest that during rowing cerebral perfusion is influenced
      significantly by the rapid fluctuations in the perfusion pressure.

PMID- 9246389
TI  - Brachial arterial blood flow during static handgrip exercise of short duration at
      varying intensities studied by a Doppler ultrasound method.
AB  - The purpose of this study was to determine forearm blood flow changes during
      static handgrip exercise at different intensities in relation to heart rate and
      blood pressure. Seven active women performed static handgrip exercise at
      intensities of 10, 30, 50 and 70% maximum voluntary contraction (MVC) in a supine
      position for 1 min. During exercise at different intensities, the brachial
      arterial blood flow (Doppler ultrasound method), calculated from vessel diameter,
      flow velocity and heart rate (measured by ECG), increased to a similar level
      (137.3 +/- 20.2-160.9 +/- 26.1 mL min-1) from pre-exercise control value (87.5 +/
      14.1 mL min-1). These increases at the lower intensities were attributable to
      increased in-flow during one cardiac cycle, whereas at the higher intensities,
      they were due to increased heart rate. Both systolic and diastolic blood pressure
      (Finapres) changes increased from 10% MVC (16.1 +/- 3.4, 9.0 +/- 1.7 mmHg) up to
      50% MVC (33.8 +/- 6.7, 25.0 +/- 4.9 mmHg), but were disproportionately more
      elevated at 70% MVC (46.1 +/- 7.9, 42.9 +/- 8.9 mmHg), suggesting neural
      vasoconstriction had occurred. Immediate post-exercise hyperaemia, used as an
      indicator of poor blood supply, became greater as the exercise intensity
      increased. These results suggest that the brachial arterial blood flow was
      maintained at a similar level during 60-s static handgrip exercise at different
      intensities by elevating the blood pressure and heart rate, which probably
      counteracted the increased intramuscular pressure and neural vasoconstriction
      occurring at the higher exercise intensity. The magnitude of the post-exercise
      hyperemic response increased as exercise level increased despite increased blood
      flow to the arm during-exercise. This suggests a worsening imbalance in oxygen
      delivery in forearm muscles at higher levels of exercise.

PMID- 9246391
TI  - Presence of angiotensin converting enzyme (ACE) activity in serum of amphibian:
      comparison with ACE activity of mammalian serum.
AB  - The occurrence of angiotensin converting enzyme (EC 3.4.15.1; ACE) was
      demonstrated for the first time in serum of newt (Triturus carnifex) and frog
      (Rana esculenta). The enzymatic activity was evidenced following hydrolysis of N
      [3-(2-furyl) acryloyl]L-phenylalanyl glycyl glycine (FAPGG), a synthetic
      substrate of ACE. The serum enzyme liberated N-[3-(2-furyl) acryloyl]L
      phenylalanine (FAP) from FAPGG. The properties of the amphibian serum enzymes
      were compared with those of swine. The amphibian serum FAPGG hydrolysing
      activities were inhibited by typical ACE inhibitors, captopril and lisinopril.
      The optimum of pH was 8.3 at 10 and 37 degrees C and the temperature optimum was
      45 degrees C. The values were similar to those of swine serum. The FAPGG
      Michaelis-Menten constants (K(m)) at 37 degrees C of amphibian serum enzymes
      (0.337 mM and 0.282 mM for frog and newt, respectively) were lower than that of
      swine (1.305 mM), but close to human serum enzyme. The K(m) values obtained at 10
      degrees C were lower than those at 37 degrees C (0.152, 0.086, and 1.029 mM for
      frog, newt, and swine serum, respectively). Amphibian sera hydrolysed bullfrog
      synthetic angiotensin I to produce angiotensin II. Captopril (50 microM)
      inhibited the production of angiotensin II.

PMID- 9246390
TI  - Transepithelial transport and cell volume control in proximal renal tubules from
      the teleost Carassius auratus.
AB  - The objective of this work was to study cell volume regulation and
      transepithelial transport in renal proximal tubules. A modified stop-flow
      technique in in vitro perfused renal proximal tubules of Carassius auratus was
      used. The rate of luminal fluid absorption and the epithelial thickness were
      measured. Isosmotic Na+ removal from the tubule lumen or addition of the
      Na+/glucose co-transport blocker phloridzin (0.5 mM) to the lumen inhibited fluid
      absorption. Only minor effects on luminal absorption were observed following: (1)
      addition of the K+ channel inhibitor BaCl2 (1 mM); (2) addition of the Cl-
      channel inhibitor MK-196 (1 mM); (3) lowering bath and perfusate HCO3- in the
      presence of 0.1 mM acetazolamide; or (4) addition of the leukotriene-D4 receptor
      antagonist L-660, 711 (20 microM). Isosmotic addition of 40 mM taurine to the
      bath inhibited the rate of fluid absorption. This effect could be partially
      overcome with the organic acid secretion inhibitors probenecid (1 mM) and
      bromcresol green (0.1 mM). Finally, administration of the 5-lipoxygenase
      antagonist ETH 615-139 (20 microM) caused a significant reduction in the rate of
      luminal absorption. In summary, tubular reabsorption is, in this preparation,
      closely linked to sodium reabsorption. In the absence of luminal amino acids most
      of this sodium uptake seems to occur in co-transport with glucose followed by
      osmotically obligated water. Eicosanoids from the 5-lipoxygenase pathway appear
      to regulate this process. Finally high concentrations of taurine in the bath
      opposed luminal fluid absorption, at least partially, by its secretion into the
      tubular lumen.

PMID- 9246392
TI  - Adenosine triphosphate treatment for meconium aspiration-induced pulmonary
      hypertension in pigs.
AB  - To investigate the pulmonary haemodynamic effects of meconium aspiration and
      subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and
      ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline
      into the right heart in doses of 0.02 to 0.80 mumol kg-1 min-1 after
      intratracheal administration of 2 mL kg-1 of human meconium. Meconium
      instillation induced significant increases in pulmonary vascular pressures and
      total and postarterial resistances calculated from pulmonary artery occlusion
      studies, but did not affect the systemic haemodynamics, except for a fall in
      heart rate and increase in central venous pressure. Infusion of ATP at the lowest
      doses (0.02 and 0.08 mumol kg-1 min-1) selectively decreased the pulmonary
      arterial pressure and vascular resistance and at 0.32 and 0.80 mumol kg-1 min-1
      reduced both the pulmonary and systemic resistances. In the lung circulation the
      increasing doses of ATP reduced preferably the arterial but also the postarterial
      resistance. Withdrawal of ATP infusion led to a significant rebound effect
      especially in the postarterial segment of the lung circulation. Meconium
      aspiration thus induces an acute, predominantly postarterial obstruction in the
      lung circulation and infusion of ATP at low doses selectively dilates the
      pulmonary vascular bed and may help to preclude elevation of capillary pressures
      in meconium aspiration-induced pulmonary hypertension.

PMID- 9246393
TI  - Salivary endothelin and its response to postural changes in humans.

PMID- 9246394
TI  - Electrophysiological evidence that the twitch contraction of guinea-pig vas
      deferens is triggered by phasic activation of P2x-purinoceptors.

PMID- 9246395
TI  - Human trunk extensor muscles physiology and ergonomics.
AB  - The paravertebral muscles (PM) act together with the hamstrings and calf muscles
      as important postural muscles. Both the histochemistry, biochemistry, strength
      and endurance of the PM were studied. Moreover attention was drawn to the
      exposure of PM, in particular the internal exposure level but to a certain degree
      repetitiveness and duration, in various job elements, and their various
      physiological acute responses. The thesis also deal with possible relations
      between the function of the PM and the magnitude of low-back trouble (LBP), and
      if PM muscle fatigue may play a role as a mediating factor for the occurrence of
      work related LBP. The lumbar PM is dominated by relatively small ST fibers with a
      well-developed network of capillaries, especially distinct in the central
      sections of PM (lumbar longissimus muscle) in females. It is remarkable that ST
      fibers are of the same size or larger compared to the FT fibers even in well
      trained subjects. Further on PM is characterized by high activity levels of
      enzymes, oxidative as well as non-oxidative, important for the resynthesis of ATP
      and CrP. Also the level of muscles glycogen concentration is high. Altogether the
      PM have seemingly a potential for different metabolic pathways which may be
      selectively activated for a given activity. The average trunk extensor MVC varies
      in the different studies from 194-342 Nm and 252-450 Nm in females and males
      respectively. This is in accordance with predictions based specific strength,
      muscle cross sections and lever arms from the literature. The large range in
      strength due to dimension, age and training have to be considered when such data
      are used for e.g. ergonomic standardization and biomechanical modelling. The sex
      difference is smaller (female:male trunk extensor strength ratio = 0.7-0.8) than
      reported earlier. The small age reduction (25-60 year) of the trunk extensor
      strength, 0.5% per year, is probably caused by the fact that the ST dominated
      musculature is less sensitive to atrophy. The results indicate that a secular
      reduction of the trunk extensor strength has occurred during the last 2-3 decades
      possibly caused by a more sedentary lifestyle, both in working life due to
      mechanization introduced gradually during that period, and in leisure time
      activity. An important finding is that the static endurance time is significantly
      larger in the trunk extensors compared to other muscles, and larger in females
      than males. Possible explanations for the findings include 1) the reported histo-
      and biochemical results, 2) favorable blood flow conditions and 3) specific
      activation strategies of the muscles constituting the PM. In the vocational
      studies manifest signs of fatigue in the lumbar paravertebral muscles, are seen,
      including changes in both the energy spectra of the surface EMG towards lower
      frequencies and increases in the RMS amplitude, reduction of the static endurance
      time, and increase in the rate of perceived exertion during a working day in
      bricklayers performing highly repetitive work with their trunk extensors
      (1000:1200 bricks per day). Similar events do also occur during standing letter
      sorting with a very low close to static exposure of PM. Ergonomic arrangements
      may have a marked reducing effect on the internal exposure of PM especially if
      the job include manual handling operations (e.g. forest work, aircraft loading),
      but it is not possible to compensate for repetitiveness, and long task duration
      by so-called "good" ergonomics (e.g. introducing mats or shoes in upright working
      operations). The chronic effects (i.e.LBP) are also studied. It is found that
      trunk extensor static endurance time in 77 postmen was related to the degree of
      LPB, but this was not the case for strength of the trunk-extensors and flexors.
      Thus, it is shown that a broad variety of work related exposures may cause muscle
      fatigue in PM. The possible aetiological role of muscle fatigue is however not
      explained. (ABSTRACT TRUNCATED)

PMID- 9246396
TI  - Cardiopulmonary complications of esophageal surgery.
AB  - This article reviews preoperative cardiopulmonary concerns that may need medical
      investigation prior to surgery. Common intraoperative hemodynamic disturbances
      and possible causes of respiratory failure are discussed. The cardiopulmonary
      complications occurring after esophagectomy reported in large series are
      presented.

PMID- 9246397
TI  - Pitfalls and complications of cricopharyngeal myotomy.
AB  - Despite a meticulous operative technique, complications still may occur following
      cricopharyngeal myotomy. In our series of 205 patients, infection was seen in 11
      patients (5.3%) with fistula formation for two patients (1.0%). These
      complications were seen more frequently in patients treated for a
      pharyngoesophageal diverticulum. Mortality directly related to the surgical
      procedure was seen in three patients (1.4%), all suffering from muscular
      dystrophy.

PMID- 9246398
TI  - Failure after esophagomyotomy for esophageal motor disorders. Causes, prevention,
      and management.
AB  - An accurate preoperative diagnosis of an esophageal motor disorder, including its
      location (the LES, the body of the esophagus, or both), is essential before
      proceeding with esophagomyotomy. The operative procedure should be performed with
      careful attention to certain technical details to ensure completeness of the
      myotomy, to prevent later healing of the myotomy, and to avoid radical
      cardiomyotomy that might facilitate the subsequent development of GER. Potential
      hazards are associated with performing a 360 degrees antireflux procedure in the
      presence of an aperistaltic esophagus. Early operation before the development of
      megaesophagus is recommended. The excellent results achieved by resection coupled
      with antrectomy and Roux-en-Y diversion suggest its wider application to patients
      with one or more previous failed myotomies, particularly patients with stricture
      and megaesophagus. Long-term surveillance of patients with achalasia is mandatory
      in view of the known risk of late development of squamous cell carcinoma.

PMID- 9246399
TI  - Pitfalls and complications of antireflux surgery. Nissen and Collis-Nissen
      techniques.
AB  - The outcome of total fundoplication surgery for GER disease is unsatisfactory in
      15% of patients. The likelihood of an unsuccessful outcome can be reduced by
      careful patient selection, which includes making an accurate diagnosis, and by
      choosing an operation that is tailored to the patient's physiology.
      Intraoperative and acute postoperative complications fortunately are rare and can
      be avoided through the use of meticulous surgical techniques. Late complications,
      including dysphagia, recurrent reflux symptoms, and delayed gastric emptying, are
      common and have a rate of reoperation of up to 10%; a systematic evaluation
      usually discloses their underlying causes. A slipped fundoplication wrap, an
      excessively tight wrap, a paraesophageal hiatal hernia, and severe recurrent
      symptoms are common indications for reoperation.

PMID- 9246400
TI  - Complications and pitfalls: Belsey and Collis-Belsey antireflux repairs.
AB  - This article reviews the histories and techniques of the Belsey and Collis-Belsey
      antireflux repair operations and discusses the complications and pitfalls
      associated with these two procedures.

PMID- 9246401
TI  - Pitfalls and complications of colon interposition.
AB  - Colon interposition is a complex operation that requires meticulous technique and
      attention to detail. In experienced hands, the colon is a valuable conduit for
      esophageal reconstruction, particularly in patients with benign disease.

PMID- 9246402
TI  - Toxicity of chemotherapy for esophageal carcinoma.
AB  - The prognosis of patients with clinically locoregional esophageal cancer is poor
      due to systemic recurrence of disease and a significant rate of local recurrence.
      Therefore, systemic chemotherapy in combination with radiation therapy and
      surgery has been evaluated extensively. Recent trials suggest a trend toward
      improved survival with the use of combined modality therapy compared with surgery
      alone. Toxicity in these trials, particularly when preoperative chemoradiotherapy
      is given, often is substantial and has tempered enthusiasm for the routine use of
      this treatment approach. The focus of recent studies is the identification of
      more active and better-tolerated systemic chemotherapy; the drug paclitaxel in
      particular is a promising new agent. In the nonsurgical, radiotherapy-based
      treatment of esophageal cancer, a combination of chemotherapy and radiation is
      superior to radiotherapy alone and now is standard treatment.

PMID- 9246403
TI  - The pitfalls and complications of radiation therapy for esophageal carcinoma.
AB  - Radiation therapy is an important part of the management of esophageal cancer.
      Effective radiation therapy, however, requires careful evaluation of the tumor
      and the patient, cognizance of the tolerance of normal tissues in the area to the
      type of chemotherapy or surgical procedure employed, detailed planning, and
      streamlined delivery. When combining radiation therapy with other modalities of
      cancer treatment, physicians of both disciplines must be aware of the ability of
      one modality to potentiate the toxicity of the other. Therapy prescribed with the
      intention to cure and achieve long-term survival must be planned with
      consideration for the quality of life of the patient.

PMID- 9246404
TI  - Complications of abdominal right-thoracic (Ivor Lewis) esophagectomy.
AB  - Esophageal resection and reconstruction are associated with significant operative
      and postoperative morbidity and mortality. Careful evaluation of the patient's
      cardiopulmonary status; proper preparation of the patient with smoking cessation,
      exercise, and cardiopulmonary rehabilitation; assessment of the stage of disease;
      selection of a suitable operative technique; and meticulous attention to
      technical details help reduce the incidence of complications and ensure a
      successful outcome in this technically challenging procedure.

PMID- 9246405
TI  - Complications of transhiatal esophagectomy.
AB  - THE is accompanied by significant operative morbidity. Most complications,
      however, are not life-threatening and, overall, this method of esophageal
      resection is safe, expeditious, effective, and physiologically well tolerated for
      patients with benign esophageal disease and for patients with cancer of the
      esophagus.

PMID- 9246406
TI  - Pitfalls and complications of left thoracoabdominal esophagectomy.
AB  - The left thoracoabdominal incision is an excellent option for approaching a
      variety of diseases in the lower esophagus and upper abdomen. If attention is
      paid to a few minor details, the incision can be placed properly and closed with
      minimal morbidity as a result of the incision itself. Routine placement of an
      epidural catheter is mandatory and allows early extubation, chest physiotherapy,
      and mobilization.

PMID- 9246407
TI  - Pitfalls and complications of esophageal prosthesis, laser therapy, and dilation.
AB  - Although often diagnosed and treated by gastroenterologists, thoracic surgeons
      should be skilled partners in the management of esophageal obstruction. Knowledge
      of pitfalls and complications of any procedure is a prerequisite to success. This
      article focuses on problems encountered in dilatation, laser ablation, and
      stenting of esophageal strictures. Dilatation of both benign and malignant
      strictures requires knowledge of the different types of dilators and the ability
      to adapt to different stricture characteristics. Although lower morbidity makes
      laser ablation of malignant obstruction attractive, this author finds its use to
      be restrictive. The advent of expandable metal stents offers the potential for
      fewer early complications when compared with plastic protheses but, as discussed,
      morbidity may be different rather than less.

PMID- 9246408
TI  - Regional differences in the compaction of chromatin in human G0/G1 interphase
      nuclei.
AB  - The large-scale structure of chromatin corresponding to G- and R-bands in human
      G0/G1 interphase nuclei was compared. Fluorescence in situ hybridization (FISH)
      was used to measure the interphase distance between 42 pairs of probes separated
      by 0.1-1.5 Mbp. The probe pairs were derived from 21q22.2 and Xp21.3, G-band
      positive regions, and from 4p16.3, 6p21.3, and Xq28, R-band positive regions.
      Distributions of measured interphase distances in all regions approximated a
      Rayleigh distribution, suggesting that the chromatin follows a random-walk path
      over this range. A linear correlation of mean-square interphase distance and
      genomic separation, also indicative of random-walk folding, was observed in all
      regions. The slope of the correlation observed using probes from G-band regions
      was systematically lower than that from R-band regions. The difference in the
      slope between Xp21.3 and Xq28 was particularly striking and was observed in
      normal fibroblast cells, fixed alternatively with methanol and acetic acid or
      paraformaldehyde, and HeLa cells. These results demonstrate regional differences
      in large-scale chromosome structure during interphase, with the more openly
      configured chromatin corresponding to R-bands.

PMID- 9246409
TI  - Comparative mapping of Xp22 genes in hominoids--evolutionary linear instability
      of their Y homologues.
AB  - Several genes located within or proximal to the human PAR in Xp22 have homologues
      on the Y chromosome and escape, or partly escape, inactivation. To study the
      evolution of Xp22 genes and their Y homologues, we applied multicolour
      fluorescence in situ hybridization (FISH) to comparatively map DNA probes for the
      genes ANT3, XG, ARSD, ARSE (CDPX), PRK, STS, KAL and AMEL to prometaphase
      chromosomes of the human species and hominoid apes. We demonstrate that the genes
      residing proximal to the PAR have a highly conserved order on the higher primate
      X chromosomes but show considerable rearrangements on the Y chromosomes of
      hominoids. These rearrangements cannot be traced back to a simple model involving
      only a single or a few evolutionary events. The linear instability of the Y
      chromosomes gives some insight into the evolutionary isolation of large parts of
      the Y chromosomes and thus might reflect the isolated evolutionary history of the
      primate species over millions of years.

PMID- 9246410
TI  - Interphase arrangement of rye B chromosomes in rye and wheat.
AB  - Probes for B chromosome-specific sequences in the distal region of the long arm
      of the rye B have been used to investigate the interphase arrangement of the Bs
      in rye and in hexaploid wheat. The Lindstrom strain of wheat carries the rye Bs
      as additions. The number of in situ signals in nuclei with two, three and four Bs
      is often less than the maximum B number, and it seems that the Bs may be grouped
      together in various ways rather than being randomly dispersed throughout the
      nucleus. The degree of physical association is greater in rye than in the allen
      wheat background. The results are discussed in relation to the pairing and
      recombination preferences of the Bs in rye and in Lindstrom wheat.

PMID- 9246411
TI  - Conserved Y-chromosomal location of TSPY in Bovidae.
AB  - We determined the chromosomal location of TSPY, the testis-specific protein, Y
      encoded, by fluorescence in situ hybridization (FISH) to chromosome spreads of
      cattle, goat and sheep. Using a cloned polymerase chain reaction (PCR) product of
      one bovine TSPY family member, we were able to show a conserved Y chromosomal
      localization for TSPY in all three species. In contrast to a limited regional
      distribution of TSPY FISH signals on the chromosome of man, other primates, great
      apes, goat and sheep, in cattle TSPY-related sequences appear to be spread over
      most of the Y chromosome. The painting effect observed in this species reflects
      the higher complexity of the bovine TSPY gene family, being composed not only of
      a tandemly repeated cluster, but harbouring a large number of different family
      members dispersed all over the Y chromosome.

PMID- 9246413
TI  - Geographical distribution of B chromosomes in the grasshopper Eyprepocnemis
      plorans, along a river basin, is mainly shaped by non-selective historical
      events.
AB  - The analysis of 19 populations of the grasshopper Eyprepocnemis plorans,
      collected along four rivers belonging to the Segura basin (Mundo, Benamor,
      Taibilla and Segura itself), has shown that the presence of B chromosomes ends
      abruptly in each river, coinciding with the existence of a narrow pass in which
      this grasshopper cannot live because of the absence of the appropriate habitats.
      The existence of a broad inland region lacking grasshoppers with B chromosomes
      suggests that B chromosomes arose after the first colonization of the Iberian
      Peninsula by E. plorans specimens from North African populations. The B
      chromosome seems to have spread upstream along each of these four rivers until
      reaching geographical barriers that have impeded its advance and thus have
      preserved the non-B chromosome region. The available evidence indicates that the
      observed geographical distribution of the B chromosome polymorphism in this zone
      was shaped mainly by historical non-selective events.

PMID- 9246412
TI  - Detection of alien chromatin conferring resistance to the beet cyst nematode
      (Heterodera schachtii Schm.) in cultivated beet (Beta vulgaris L.) using in situ
      hybridization.
AB  - Chromatin originating from wild beets of the genus Beta, section Procumbentes,
      has been investigated in nematode-resistant hybrid-derived lines of sugar beet
      (Beta vulgaris L.) by in situ hybridization using satellite, telomeric and
      ribosomal DNA repeats, a yeast artificial chromosome (YAC) and total genomic DNA
      as probes. The allen chromosome was detected in three monosomic addition lines
      (2n = 18 + 1) by genomic in situ hybridization. Fluorescence in situ
      hybridization with a genome-specific satellite repeat and YAC DNA enabled the
      visualization of Procumbentes chromosomes, and in double-target hybridization it
      was shown that they do not carry 18S-5.8S-25S rRNA and 5S rRNA genes. The wild
      beet-specific satellite repeat and the telomere sequence from Arabidopsis
      thaliana were used to perform a structural analysis of the wild beet chromosome
      fragments of two resistant fragment addition lines. It was shown that one
      physical end of the chromosome fragments consists of telomeric repeats.
      Comparison of fragment sizes indicated that the small chromosome fragments
      harbouring the resistance gene most likely resulted from the loss of one wild
      beet chromosome arm and an internal deletion of the remaining arm.

PMID- 9246414
TI  - Comparative FISH-mapping of villin (VIL) gene in river buffalo, sheep and goat
      chromosomes.
AB  - Two genomic clones of the villin (VIL) gene were independently hybridized on
      river buffalo (Bubalus bubalis, BBU), sheep (Ovis aries, OAR) and goat (Capra
      hircus, CHI) chromosomes by using sequential fluorescence in situ hybridization
      (FISH) and R-banding (RBP- and RBA-banding). Clear hybridization signals revealed
      that VIL is located in BBU 2q33, OAR 2q33 and CHI 2q33. These chromosomes and
      chromosome bands are believed to be homologous and the VIL locus is the same as
      that previously found on cattle chromosome 2q43. VIL localization in these three
      species allows us tentatively to assign all cattle U17 to BBU and CHI 2q and to
      extend the physical map to OAR 2q.

PMID- 9246415
TI  - Differences in the chromosomal distribution of telomeric (TTAGGG)n sequences in
      two species of the vespertilionid bats.

PMID- 9246416
TI  - Visualizing human 5S rDNA.

PMID- 9246417
TI  - Site-specific base deletions in human alpha-satellite monomer DNAs are associated
      with regularly distributed CENP-B boxes.

PMID- 9246418
TI  - 1H-NMR analysis of trimethylamine in urine for the diagnosis of fish-odour
      syndrome.
AB  - This paper reports the use of proton NMR spectroscopy for the analysis of
      trimethylamine in the urine of a patient with trimethylaminuria. Analysis of this
      compound was also performed for other members of his family. Qualitative and
      quantitative determination of trimethylamine and trimethylamine-N-oxide was
      simultaneously performed on untreated urine within a few minutes. The application
      of the method is discussed.

PMID- 9246419
TI  - Tocopherol in inborn errors of intermediary metabolism.
AB  - Red blood cell tocopherol was measured in a group of 92 children with inborn
      errors of intermediary metabolism to evaluate the peroxidative damage in
      different mitochondrial and cytosolic defects, and to consider the need for
      treatment or vitamin supplementation. Tocopherol was determined by HPLC with UV
      detection. Results were expressed in nanomoles red blood cell tocopherol per gram
      protein. Significant differences (Mann-Whitney; P < 0.001) were found between
      tocopherol levels in untreated patients: 19 with mitochondrial defects versus 23
      with cytosolic enzyme or transport defects, and versus 58 age-matched reference
      values. In conclusion, mitochondrial enzyme deficiencies, either amino and
      organic acidurias or defects of energy metabolism, seem to produce an excess of
      free radicals with the consequent utilization of tocopherol as antioxidant. This
      is not apparent in the cytosolic enzyme defects studied, whose tocopherol levels
      are in the normal range. Treatment with tocopherol completely corrects the
      deficient antioxidant status.

PMID- 9246420
TI  - In vitro effects of an azo compound on the haemolysis and unsaturated fatty acids
      of red blood cells.
AB  - Human red blood cells were treated with 4,4'-azo-bis-(4-cyanovaleric acid) (0-27
      x 10(-3) M) in order to determine the effect of the compound on red blood cell
      haemolysis and unsaturated fatty acids. Maximum haemolysis amounting to
      approximately 100%, occurred after 60 min incubation with 15 x 10(-3) M azo
      compound and did not change to any significant extent by increasing incubation
      time to 4 h. The azo compound caused a decrease in unsaturated fatty acids
      unrelated to the number of double bonds. The percentage loss of unsaturated fatty
      acids was 60-100. Therefore the present study reveals that incubation of red
      blood cells with 15 x 10(-3) M 4,4'-azo-bis-(4-cyanovaleric acid) for 1 h causes
      maximum haemolysis. Also the damaging effect of the compound on red blood cell
      unsaturated fatty acids is parallel to haemolysis. These results show that this
      compound might have relevance for pathophysiology of red blood cells.

PMID- 9246422
TI  - Comparison of urinary and plasma malondialdehyde in preterm infants.
AB  - The measurement of malondialdehyde (MDA) in biological fluids remains a popular
      method for the quantification of free radical damage to lipids in vivo. Several
      diseases of prematurity are thought to be related to oxidative injury and
      previous studies have found elevated MDA in plasma and urine in preterm infants.
      Our aim was to investigate the relationship between plasma and urinary MDA levels
      in preterm infants during the first week of life using a high-performance liquid
      chromatography (HPLC) based, thiobarbituric acid (TBA) assay with paired plasma
      and urine samples. We obtained 50 paired samples, and were unable to demonstrate
      a relationship between the two parameters after the first day of life. In 18
      cases a further urine sample was collected 24 h later. There was a positive
      correlation (r = 0.54, P = 0.02) between plasma MDA and urinary MDA 24 h later.
      The finding that plasma changes in MDA are reflected in urine 24 h later
      validates the use of urinary MDA as a marker of whole body lipid peroxidation in
      populations without renal disease.

PMID- 9246421
TI  - Assessment of the performance of a capture immunoassay for the bone isoform of
      alkaline phosphatase in serum.
AB  - We report the analytical validation of an immunocapture assay for the bone
      isoform of alkaline phosphatase in serum. A between batch imprecision of less
      than 10% was found, being about 8% at the upper limit of the reference range, and
      with a detection limit of 0.8 IU/l at 37 degrees C. The crossreactivity of the
      method with the liver isoform was found to be in the range of 3-13% depending on
      the method employed. Unexpectedly the correlation of results with a non
      immunological method for the quantitation of bone ALP showed significant
      differences between samples from children and patients with Paget's disease, with
      an apparent lower level of capture in the case of children. These data suggest
      that there may be differences in the epitope recognised by the antibody, which
      may be due to the presence of different forms of bone enzyme in these two
      populations. The significance of these observations is not clear at this stage.

PMID- 9246424
TI  - An analytical method for the quantitation of mannitol and disaccharides in serum:
      a potentially useful technique in measuring small intestinal permeability in
      vivo.
AB  - An electrochemical-HPLC method for the determination of mannitol and lactulose is
      presented which may facilitate routine testing of intestinal permeability by
      requiring only a single blood sample instead of a 6-hour urine collection.
      Chromatographic conditions are described which allow separation of the closely
      related sugars lactulose and the dietary disaccharides lactose and sucrose.
      Preliminary results in normal controls and patients with untreated coeliac
      disease are presented.

PMID- 9246423
TI  - Carbamazepine levels in the hair of patients under long-term treatment: a
      preliminary study.
AB  - Carbamazepine (CBZ) levels in the scalp hair of seventeen patients (ten male and
      seven female), aged from five to forty years old, receiving the drug
      systematically were determined after hair dissolution and solid-phase extraction
      procedures using both immunoassay (Abbott TDx) and gas chromatographic (GC)
      techniques. Carbamazepine levels in hair ranged from 13.9 to 66.3 micrograms/g
      (mean 26.6 micrograms/g, median 20.9 micrograms/g) according to GC measurements.
      The immunoassay technique gave slightly higher results (mean 28.0 micrograms/g,
      median 22.1 micrograms/g). The blood concentrations of carbamazepine, using
      immunoassay (Abbott TDx) technique, ranged from 2.9 to 10.7 micrograms/ml (mean
      6.2 micrograms/ml, median 5.7 micrograms/ml). Our data indicate the possible use
      of hair testing as a marker of the dosage history of patients under long-term
      treatment with CBZ.

PMID- 9246425
TI  - Soluble highly coloured phenylboronic acids and their use in glycohemoglobin
      quantification.
AB  - Water soluble dye-phenylboronic acid conjugates (dye-PBAs) possessing strong
      absorption of visible light are introduced as new reagents for the determination
      of glycohemoglobin. Their functionality and prospective use are demonstrated in a
      semi-homogenous glycohemoglobin assay. The assay is based on cis-diol
      esterification of dye-PBA to glycohemoglobin followed by selective precipitation
      of hemoglobin from solution, co-precipitating bound dye-PBA. Quantification of
      the molar "dye-PBA/Hb"-ratio in redissolved precipitates using either absorption
      or fluorescence spectroscopy, reflects the glycation level of the blood samples
      used. Future development of the assay principle is illustrated in a filter based
      assay, collecting the precipitated hemoglobin on a filter followed by
      reflectometric readings directly on the precipitate. The significance of this
      work lies first, in the demonstration of a new principle for the determination of
      glycohemoglobin, and second, as an illustration of the prospective use of water
      soluble, signal-forming non-immobilised boronic acids in the determination of cis
      diol containing analytes.

PMID- 9246426
TI  - Commutability between stabilized materials and fresh human serum to improve
      laboratory performance.
AB  - With the recent advances in laboratory technology, many quality-related problems
      have been improved. However, the issue of commutability, a factor that greatly
      affects daily decisions concerning patient status, still remains to be solved.
      This paper determines the commutability between 27 stabilized materials (controls
      and calibrators) and clinical specimens for five serum quantities, using carrier
      bound reagent chemistry and conventional wet methods. Our aim was to pinpoint the
      specific problems related to non-commutable calibrators and controls in our
      setting, and minimize their effect in daily practice. We found major difficulties
      in selecting appropriate accuracy controls in carrier-bound reagent techniques,
      and in finding materials commutable for several analytes simultaneously. Several
      suggestions for reducing problems related to non-commutability, such as
      procedures for assigning values to multicalibrators, are proposed. We explain the
      apparent incongruencies observed in daily quality surveillance, when data from
      different control materials (internal quality control and external quality
      assessment) are evaluated. The conclusions emphasize the need for a combined
      effort (manufacturers, organizers of external quality assessment schemes and
      individual laboratories) to find the cause of, and eliminate, the negative
      repercussions on laboratory performance produced by non-commutability.

PMID- 9246427
TI  - The effect of delta-gluconolactone, an oxidised analogue of glucose, on the
      nonenzymatic glycation of human and rat haemoglobin.
AB  - Nonenzymatic glycation of proteins and oxidative stress are considered
      independent factors important in the development of the complications of diabetes
      but may be interrelated by the process of autoxidative glycation. This pathway
      involves monosaccharide autoxidation to a reactive ketoaldehyde analogue and
      subsequent reaction with protein to form a ketoimine adduct. This study
      demonstrates that delta-gluconolactone (delta-GL), an oxidised analogue of
      glucose, is a potent glycating agent in vitro of haemoglobin present in blood
      samples from insulin-dependent diabetic and non-diabetic human subjects and from
      spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) rats. The
      percentage glycated haemoglobin after incubation (37 degrees C, 5 h) with delta
      GL (25 mmol/l) was significantly (P < 0.002) higher than that observed using an
      equimolar concentration of glucose. Intravenous administration of delta-GL (1
      g/kg) to non-diabetic BB/E rats also significantly increased glycation of
      haemoglobin (6.0 +/- 0.1% vs 4.9 +/- 0.1%, P < 0.01) whereas intravenous
      injection of an identical dose of glucose had no significant effect (5.1 +/- 0.1%
      vs 5.0 +/- 0.2%). These results support the hypothesis that nonenzymatic
      glycation of proteins involves attachment by both native and oxidised
      monosaccharides. Further investigation of the interactions between diabetes
      associated increases in oxidative stress and glycation on the development and
      progression of the vascular complications of diabetes is necessary.

PMID- 9246428
TI  - Evaluation of the genotyping and phenotyping approaches in the investigation of
      apolipoprotein (a) size polymorphism.
AB  - Apoprotein (a) size polymorphism was evaluated at the genotypic and phenotypic
      level in 110 individuals. Both methods were well correlated with respect to size
      (r = 0.971), providing that the protein size was expressed as a number of kringle
      4 repeats. Despite the fact that the immunoblotting method used was sensitive
      enough to detect less than 1 ng of lipoprotein (a), 62 samples had single-band
      phenotypes and one sample had no detectable band, whereas only seven samples had
      single-band genotypes. The mean size of the alleles coding for the undetected
      isoforms was significantly larger (141 kb) than for the detected isoforms (123
      kb), corroborating the earlier finding of an inverse relationship between the
      size and the plasma expression level of apoprotein (a). Furthermore, increasing
      detectability was achieved by loading the gel with different amounts of plasma
      for each sample. Our results indicate that genotyping is more resolving and more
      sensitive, but requires a more specialized technology. Phenotyping was carried
      out using commercially available reagents.

PMID- 9246429
TI  - Cortical plasticity underlying perceptual, motor, and cognitive skill
      development: implications for neurorehabilitation.

PMID- 9246430
TI  - What words are telling us about the brain.
AB  - Modern functional brain imaging with PET and fMRI provides a new perspective on
      the organization of language in the human brain. A better definition of the
      distributed nature of the brain circuits involved, an appreciation of the
      flexibility of these circuits in adapting to the different aspects of speech
      production, an identification of areas not previously associated with the
      cognitive aspects of language, and a new understanding of the implications of
      specific brain lesions on the lives and behavior of patients are all early
      suggestions of the benefits to be derived from this work. Much exciting work lies
      ahead.

PMID- 9246431
TI  - Neural mechanisms for heading and structure-from-motion perception.

PMID- 9246432
TI  - Visual responses in V1 of freely viewing monkeys.

PMID- 9246433
TI  - Amblyopia: a developmental disorder of the central visual pathways.

PMID- 9246434
TI  - The functional anatomy of visual awareness.

PMID- 9246435
TI  - A single locus, RGHT, specifies preference for hand utilization in humans.

PMID- 9246436
TI  - Functions and roles of glutamate receptors in synaptic transmission and
      plasticity.

PMID- 9246437
TI  - Combination of gene targeting and gene transfer by adenoviral vectors in the
      analysis of neurotrophin-mediated neuronal plasticity.

PMID- 9246438
TI  - Neurotrophins in cortical development.

PMID- 9246439
TI  - In vivo development of neuronal structure and function.

PMID- 9246440
TI  - Cortical dynamics and visual perception.

PMID- 9246441
TI  - What neurological syndromes can tell us about human nature: some lessons from
      phantom limbs, capgras syndrome, and anosognosia.

PMID- 9246442
TI  - The molecular biology of olfactory perception.

PMID- 9246443
TI  - Information coding in the mammalian olfactory system.

PMID- 9246444
TI  - Olfactory recognition and discrimination in Caenorhabditis elegans.

PMID- 9246445
TI  - Genetic approaches to mammalian olfaction.

PMID- 9246446
TI  - Biochemical and transgenic analysis of gustducin's role in bitter and sweet
      transduction.

PMID- 9246447
TI  - Memory, memory impairment, and the medial temporal lobe.
AB  - The cognitive and neuroanatomical work described here should be viewed as a first
      step in analyzing how the brain has organized its memory functions, which can
      open the door to more detailed neurobiological analysis. With respect to
      declarative memory, it should soon be possible to study representations directly
      in neocortex with the technique of single-cell recording, to observe directly the
      development of neuronal plasticity important for declarative memory, and to
      determine how the medial temporal lobe interacts with neocortex during learning,
      consolidation, and retrieval. In this regard, the paradigms developed by
      Miyashita and his colleagues appear to hold particular promise (Sakai and
      Miyashita 1991; Higuchi and Miyashita 1996). With respect to nondeclarative
      memory, it is now possible to identify particular brain systems that are
      essential for particular kinds of memory. An important next step will be to
      determine whether these systems are essential for the acquisition, storage, or
      expression of memory, and to identify exactly where the synaptic changes occur
      that support each kind of memory.

PMID- 9246448
TI  - Neural mechanisms of declarative memory.

PMID- 9246449
TI  - A return to genetic dissection of memory in Drosophila.

PMID- 9246450
TI  - CaMKII function in the nervous system explored from a genetic perspective.

PMID- 9246451
TI  - Hippocampal CA1-region-restricted knockout of NMDAR1 gene disrupts synaptic
      plasticity, place fields, and spatial learning.

PMID- 9246452
TI  - Genetic analysis of function and dysfunction in the central nervous system.

PMID- 9246453
TI  - Emotional memory: a search for sites of plasticity.

PMID- 9246454
TI  - Neurobiology of memory for emotional events: converging evidence from infra-human
      and human studies.

PMID- 9246455
TI  - A Drosophila circadian clock.

PMID- 9246456
TI  - Molecular anatomy of a light-sensitive circadian pacemaker in Drosophila.

PMID- 9246457
TI  - Rhythmic transcription and autoregulatory loops: nuclear pacemaker CREM.

PMID- 9246458
TI  - Forward genetic approaches to circadian clocks in mice.
AB  - The study of mammalian circadian rhythms has a rich history of physiological
      understanding, but the molecular elements of the mammalian clock remain to be
      discovered. Availability of effective mutagenesis procedures and mouse molecular
      genetics resources sufficient for the task of positional cloning give cause for
      hope that the Clock gene, as well as other components of the mammalian circadian
      system, will be identified soon. The isolation of Clock in a deliberate
      mutagenesis screen provides an important proof-of-principle that forward genetics
      can be successfully applied toward the discovery of novel genes underlying
      complex behaviors in mice.

PMID- 9246459
TI  - Confocal-microscopic visualization of membrane addition during synaptic
      exocytosis at presynaptic active zones of hair cells.

PMID- 9246460
TI  - Multiple myosin isozymes and hair-cell function.

PMID- 9246461
TI  - Molecular and cellular plasticity in developing epileptic brain.
AB  - Defined transgenic models of epilepsy in the mouse represent unique opportunities
      to examine interactions between synchronous synaptic activity and cellular
      programs of brain development. We are beginning to acquire a list of the kinds of
      genes favoring sudden, intermittent aberrant discharges in central neurons, and
      we have found that, rather than arising from a few gene superfamilies regulating
      membrane excitability, they are involved in many diverse functions of the cell.
      Whereas some primary gene defects impinge directly on membrane electrogenesis and
      neurotransmitter signaling at synapses, others are too far removed from these
      processes to clearly visualize the steps by which they promote epileptogenesis.
      We have tantalizing evidence that several, and probably all, epilepsy genes
      entrain some degree of secondary molecular and cellular plasticity, and we can
      guess that these downstream rearrangements may account for the delayed onset of
      epileptic phenotypes in some syndromes. It is too early to tell whether these, or
      other induced changes, provide the basis for the reversibility of some
      epilepsies. The diversity of epilepsy genes and their intervening cellular
      phenotypes promise to provide a rich source of novel molecular targets for
      therapeutic discovery and will have a lot to teach us in the future about the
      developmental potential of neural circuits in the mammalian brain.

PMID- 9246462
TI  - Glutamate receptor autoimmunity in Rasmussen's encephalitis.

PMID- 9246463
TI  - Molecular and genetic insights into ligand binding and signal transduction at the
      inhibitory glycine receptor.

PMID- 9246464
TI  - Nicotinic receptors and brain plasticity.

PMID- 9246465
TI  - The nicotinic acetylcholine receptor at the neuromuscular junction: assembly and
      tyrosine phosphorylation.

PMID- 9246466
TI  - The GluR2 hypothesis: Ca(++)-permeable AMPA receptors in delayed
      neurodegeneration.
AB  - Increased glutamate-receptor-mediated Ca++ influx is considered an important
      factor underlying delayed neurodegeneration following ischemia or seizures. Until
      recently, the NMDA receptor was the only glutamate receptor known to be Ca(++)
      permeable. It is now well established that glutamate receptors of the AMPA type,
      encoded by a gene family designated GluR1-GluR4, exist in both Ca(++)-permeable
      and Ca(++)-impermeable forms, depending on their subunit composition and degree
      of RNA editing. Recombinant channels assembled without GluR2 are permeable to
      Ca++; channels assembled with (edited) GluR2 are Ca(++)-impermeable. AMPA
      receptors in most adult neurons are hetero-oligomers containing GluR2 subunits,
      but some neurons have GluR2-less, Ca(++)-permeable receptors. The "GluR2
      hypothesis" predicts that a relative reduction in the expression of GluR2 results
      in enhanced Ca++ influx through newly synthesized AMPA receptors, thereby
      increasing neurotoxicity of endogenous glutamate. Recent observations indicate
      reduction in GluR2 expression and predict formation of Ca(++)-permeable AMPA
      receptors following global ischemia and kainate-induced status epilepticus; these
      changes are likely to be a major factor contributing to the delayed
      neurodegeneration that follows these pathological events. The delayed
      neurodegeneration appears to be primarily apoptotic. Thus, there are at least
      three strategies for neuroprotection: block of formation of GluR2-less receptors,
      which may be possible at several levels; block of the GluR2-less receptors
      themselves; and block of the subsequent apoptosis.

PMID- 9246467
TI  - Zinc neurotoxicity may contribute to selective neuronal death following transient
      global cerebral ischemia.

PMID- 9246468
TI  - A signaling endosome hypothesis to explain NGF actions: potential implications
      for neurodegeneration.

PMID- 9246469
TI  - Neurotrophins and their p75 receptor.

PMID- 9246470
TI  - Nitric oxide, cell multiplication, and cell survival.

PMID- 9246471
TI  - The role of neuregulin (ARIA) at the neuromuscular junction.

PMID- 9246472
TI  - The receptor tyrosine kinase MuSK is required for neuromuscular junction
      formation and is a functional receptor for agrin.

PMID- 9246473
TI  - GDNF is required for kidney development and enteric innervation.

PMID- 9246474
TI  - Neuregulins as potential drugs for neurological disorders.

PMID- 9246475
TI  - Molecular biology and genetics of prion diseases.

PMID- 9246476
TI  - Prion protein structure and scrapie replication: theoretical, spectroscopic, and
      genetic investigations.

PMID- 9246477
TI  - The role of PrP in pathogenesis of experimental scrapie.

PMID- 9246478
TI  - A new variant of Creutzfeldt-Jakob disease: neuropathological and clinical
      features.

PMID- 9246479
TI  - Abnormal plasma membrane properties and functions in prion-infected cell lines.
AB  - A long trail of evidence indicates that the formation of PrPSc or its
      accumulation causes the neuronal dysfunction and clinical features of prion
      diseases. The results of our current line of studies argue that the main
      neuropathological and clinical features of prion diseases are explained by
      altered ion channel function secondary to decreased plasma membrane fluidity.
      This kind of mechanism has the potential to functionally disconnect neuronal
      networks and cause neuronal vacuolation. Our laboratory is currently focusing its
      investigations on pathogenic mechanisms that have the potential to link the
      formation of PrPSc with plasma membrane abnormalities in prion diseases. In
      summary, the first hypothesis suggests that the conversion of PrPC to PrPSc
      affects plasma membrane fluidity directly, which secondarily alters the
      properties and functions of its components. In contrast, the second hypothesis
      argues that PrPSc accumulation alters the ability of chaperones to correctly fold
      plasma-membrane proteins during their synthesis, which directly affects the
      properties of nascent proteins and secondarily affects membrane fluidity. Our
      current investigations are attempting to determine which of these mechanisms are
      plausible and, then, which is primary.

PMID- 9246480
TI  - Prions of yeast, [PSI] and [URE3], as models for neurodegenerative diseases.

PMID- 9246481
TI  - The role of presenilin 1 in the genetics of Alzheimer's disease.
AB  - Approximately 75% of AD patients have an onset of the disease after the age of 60
      years, and 60% of AD patients have no family history of the disease. Some cases
      of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene
      on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome
      1 have all been characterized as genes in which mutations lead to familial EOAD.
      For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor
      for developing AD. However, 35-50% of all AD patients do not have an epsilon 4
      allele. Other loci contributing to LOAD remain to be mapped and characterized. As
      in other complex disorders, these additional loci may involve genetic
      interactions with the known AD loci. Identification of all susceptibility loci
      for AD is a major goal in resolving the pathogenesis of AD.

PMID- 9246483
TI  - Molecular dissection of the neurofibrillary lesions of Alzheimer's disease.

PMID- 9246482
TI  - Two homologous genes causing early-onset familial Alzheimer's disease.

PMID- 9246484
TI  - Neuronal sorting and processing of amyloid precursor protein: implications for
      Alzheimer's disease.

PMID- 9246485
TI  - Cell biology of the beta-amyloid precursor protein and the genetics of
      Alzheimer's disease.

PMID- 9246486
TI  - Protein: protein interactions in Alzheimer's disease and the CAG triplet repeat
      diseases.

PMID- 9246487
TI  - Myotonic dystrophy: discussion of molecular mechanism.

PMID- 9246488
TI  - Huntington's disease.

PMID- 9246489
TI  - Targeted inactivation of the mouse Huntington's disease gene homolog Hdh.

PMID- 9246490
TI  - Polyglutamine expansions and neurodegenerative diseases.

PMID- 9246491
TI  - Toward understanding polyglutamine-induced neurological disease in
      spinocerebellar ataxia type 1.

PMID- 9246492
TI  - Molecular mechanisms for Charcot-Marie-Tooth disease and related demyelinating
      peripheral neuropathies.

PMID- 9246494
TI  - The molecular basis of fragile X syndrome.

PMID- 9246493
TI  - Connexin32 and X-linked Charcot-Marie-Tooth disease.

PMID- 9246495
TI  - Molecular characterization of the protein products of the fragile X syndrome gene
      and the survival of motor neurons gene.

PMID- 9246496
TI  - ALS: molecular clues to the jigsaw puzzle of neuronal degeneration.

PMID- 9246497
TI  - Neurofilaments, radial growth of axons, and mechanisms of motor neuron disease.

PMID- 9246498
TI  - Neurodegenerative diseases and model systems.

PMID- 9246499
TI  - Extracellular proteases in neuronal function and degeneration.

PMID- 9246500
TI  - Molecular analysis of neurotransmitter transport into secretory vesicles.
AB  - Molecular cloning of the transport proteins involved in packaging monoamines and
      ACh into secretory vesicles has implicated their activity in neural degeneration
      as well as signaling. Future studies will explore further the mechanism of active
      transport, its regulation, and the membrane trafficking of the proteins with the
      long-term goal of understanding how the regulation of transmitter release and, in
      particular, quantal size influences information processing and behavior. In
      addition, the bioenergetics of vesicular GABA and glutamate transport suggests
      that the proteins responsible for these activities may belong to a distinct gene
      family.

PMID- 9246501
TI  - AIDS dementia complex: a complex, slow virus "model" of acquired genetic
      neurodegenerative disease.

PMID- 9246502
TI  - Quantitative trait loci mapping in mouse models of complex behavior.

PMID- 9246503
TI  - Recent developments in the genetics of bipolar disorder.

PMID- 9246504
TI  - The serotonin transporter gene and affective disorder.

PMID- 9246505
TI  - The Johns Hopkins University Collaborative Schizophrenia Study: an epidemiologic
      genetic approach to test the heterogeneity hypothesis and identify schizophrenia
      susceptibility genes.

PMID- 9246506
TI  - Molecular genetic studies of schizophrenia.

PMID- 9246507
TI  - Support for schizophrenia vulnerability loci on chromosomes 6p and 8p from Irish
      families.

PMID- 9246508
TI  - Genotype and phenotype analysis at the 22q11 schizophrenia susceptibility locus.

PMID- 9246509
TI  - Searching for susceptibility genes in schizophrenia by genetic linkage analysis.

PMID- 9246510
TI  - Secondary craniofacial management following initial correction of nonsyndromic
      craniosynostosis.
AB  - Marked technical improvements in the surgical management of craniosynostosis have
      come hand-in-hand with refinements in anesthesia, intensive care, and
      radiographic image analysis. At the beginning of the second century of the care
      of these patients, we now have a variety of sophisticated options that represent
      safer, more physiologically sound and aesthetically more pleasing options for the
      correction of secondary problems in craniosynostosis.

PMID- 9246512
TI  - Secondary craniofacial management following skeletal correction in facial
      asymmetry. Application of microsurgical techniques.
AB  - Based upon our experience with microvascular reconstruction of facial contour
      problems in 116 patients, we have developed an operative approach that emphasized
      both donor site and facial aesthetics and reliably restores symmetry. This allows
      correction of the obvious facial symmetry along the jawline as well as the more
      subtle problems in the midface, temporal, and periorbital areas. A state-of-the
      art approach for reconstruction of facial deformities should include standard
      craniofacial techniques with or without bone expansion followed by soft-tissue
      microvascular reconstruction when required. This marriage of both hard and soft
      tissue maximizes the aesthetic results by restoring facial harmony in these
      difficult craniofacial patients.

PMID- 9246511
TI  - The craniofacial dysostosis syndromes. Staging of reconstruction and management
      of secondary deformities.
AB  - During the past several decades, since the introduction of craniofacial surgery
      by Dr. Tessier in 1967, craniomaxillofacial surgery has advanced in many ways.
      Craniosynostosis is a common craniofacial malformation and requires a thoughtful
      team approach to select the preferred timing and technical aspects of
      reconstruction. The current approach to the correction of the deformities
      associated with the craniofacial dysostosis syndromes is to stage the
      reconstruction to coincide with facial growth patterns, visceral function, and
      psychosocial development. Recognition of the need for a staged reconstructive
      approach serves to clarify the objectives of each phase of treatment both for the
      clinicians and family. By continuing to define our rationale for the timing,
      method, and extent of surgical intervention and then objectively evaluating both
      functional and morphologic outcomes, we will improve the outlook for patients
      affected by these disorders.

PMID- 9246513
TI  - Craniofacial microsomia. A primary or secondary surgical treatment program.
AB  - Craniofacial microsomia is a complex deformity involving the craniofacial
      skeleton and the overlying soft tissues. This article discusses treatment
      programs with consideration of the variability in several anatomic areas and the
      severity of the deformity. A classification system for mandibular pathology is
      described.

PMID- 9246514
TI  - Secondary management of congenital and acquired craniomaxillofacial deformities.
      Individualized treatment planning.
AB  - Late treatment of craniofacial disorders with concomitant abnormalities of the
      jaw are the most challenging cases a craniofacial surgeon faces. This article
      details the principles of preoperative, individualized treatment planning using
      anthropometric guidelines in a simple but systematic scheme for facial analysis.
      Seventeen skeletally mature patients without cleft lip and palate or hemifacial
      microsomia, aged 15 to 65 years, underwent simultaneous orthognathic and
      craniofacial surgery for a variety of complex craniofacial disorders. The basic
      clinical approaches outlined in this article permit the surgeon to develop a
      flexible but accurate treatment plan and proceed with confidence in the
      management of patients with widespread craniomaxillofacial deformities.

PMID- 9246515
TI  - Adverse outcomes in orthognathic surgery and management of residual problems.
AB  - Adverse outcomes in orthognathic surgery include both functional and aesthetic
      components that frequently coexist. Reasons for this occurrence are
      multifactorial and can be classified in broad categories of diagnosis, treatment
      planning, technical execution, and unpreventable outcomes. Management of the
      residual deformities is both functional and aesthetic as based on correctly
      delineating the problem and its cause.

PMID- 9246516
TI  - Problems following genioplasty. Diagnosis and treatment.
AB  - Both alloplastic and osteoplastic genioplasty harbor the potential for outcomes
      that may mandate a revision. A successful reversal of this often enigmatic
      situation requires a thorough and trenchant analysis of the clinical condition,
      as well as the emotional motive leading the patient to seek a revision surgery.
      The selected corrective procedure has to offer the highest potential for success
      with the least invasion possible. The goals should be set with the scar tissue,
      distorted anatomy, and reduced circulation in mind. The limitations should be
      recognized, and the related concerns should be shared with the patient. Many of
      these, often imperfections and sometimes gross deformities, can be corrected, as
      long as the problem is identified and a suitable solution is culled out.

PMID- 9246517
TI  - The influence of Paul Tessier on our current treatment of facial trauma, both in
      primary care and in the management of late sequelae.
AB  - This article describes Paul Tessier's influence on craniofacial surgeons and
      their treatment of facial trauma. It also outlines his direct contributions to
      primary and late treatment of facial fractures.

PMID- 9246519
TI  - Enophthalmos revisited.
AB  - As an alternative to the conventional craniofacial approach with its coronal
      incision, a limited access technique has evolved. Its advantages and
      disadvantages are discussed. The method should not be used unless one is well
      versed in the correction of enophthalmos and has previous experience using the
      traditional craniofacial approach.

PMID- 9246518
TI  - Current treatment of post-traumatic deformities. Residual orbital, adnexal, and
      soft-tissue abnormalities.
AB  - Evaluation and treatment of residual post-traumatic deformities of the
      periorbital region are approached best by systematically dividing the area into
      zones and assessing the deformities and needs of that particular region before
      addressing restoration of both function and cosmesis. These zones can be extended
      three dimensionally, and all abnormalities can be addressed appropriately. Bone
      malpositioning must be addressed first, and once repositioned, many soft tissue
      abnormalities may not require treatment. All periocular zones contain specialized
      structures that are interrelated. A fundamental understanding of the anatomy and
      physiology combined with the basic plastic surgical concept of recreation of the
      defect can lead to a successful approach to late deformities in this region.

PMID- 9246521
TI  - Secondary deformities following mandibular reconstruction.
AB  - Restoration of secondary deformities following mandible reconstruction is a
      difficult challenge. Prevention is sometimes possible by careful planning, but
      frequently these problems are unavoidable. Thoughtful analysis of the deformity
      and individualized treatment planning are key ingredients of proper management.

PMID- 9246520
TI  - Strategies for the treatment of enophthalmos.
AB  - The surgical correction of post-traumatic enophthalmos is among the most
      challenging problems for the surgeon. A thorough understanding of orbital anatomy
      and the purposed mechanisms of enophthalmos is crucial to the ultimate success or
      failure of the procedures. The successful orbital reconstruction begins with a
      careful physical examination of the patient that is attentive to ocular function,
      soft-tissue position, and visible or palpable defects of the facial skeleton. The
      physical examination combined with thin section CT scanning in the axial and
      coronal planes provides the basis of the operative plan. The anatomy of the
      deformity should dictate the anatomy and shape in the surgical correction. In
      many cases, multiple surgical incisions will be required; therefore, care must be
      taken to maximize exposure and minimize the cosmetic problems associated with
      large incisions. We advocate a step-wise approach consisting of mobilization of
      the soft tissues in the area of the fracture, repositioning of the anterior and
      middle sections of the bony orbit, and reattachment of the soft tissue to the
      bone at the proper location. The approach to reconstruction of the bony orbit
      that we advocate is to first sequentially reposition each segment of the rim,
      carefully examining each articulation. Once rim reconstruction is complete,
      reconstruction of the internal wall is performed. Recall that the largest source
      of error is in inadequate reduction of the orbital rim, owing to the fact that
      this error is "squared" (according to the model) in the computation of the
      orbital volume. Through the application of these principles, the cosmetic and
      functional sequelae of post-traumatic enophthalmos can be improved greatly with
      minimal complications.

PMID- 9246522
TI  - Secondary craniofacial problems following skull base surgery.
AB  - Skull base wounds remain the most challenging that a skull base surgeon faces
      because of the unique and unforgiving requirements of the intracranial
      compartment. To successfully reconstruct these defects after complex exposure and
      radical resection around vital structures, a most conservative approach must be
      taken (i.e., one must choose the option that has the greatest chance to be
      successful, even if it means taking the extra time and effort of doing a free
      tissue transfer). Indeed, one can take no short cuts if the skull base would be
      left with a tenuous repair. Close postoperative surveillance of the patient for
      complications and maximal medical management is essential. Because of the
      difficulty of examining the hidden skull base wound postoperatively, surgeons
      must have a low threshold for re-exploration if a complication is suspected. As
      the first decade of the multidisciplinary skull base team approach passes, and
      long-term results are being assessed, the question of "is it worth it?" is fair.
      The reported series are showing increased survival rates and decreased
      complication rates. Therefore, the answer would appear to be "yes". The question
      is best answered, however, by the individual patient who previously had no hope
      for treatment of his or her deep-seated skull base tumor.

PMID- 9246523
TI  - The treatment of secondary and residual dentofacial deformities in the cleft
      patient. Surgical and orthodontic therapy.
AB  - The methods described to manage secondary jay deformities, resulting
      malocclusion, residual oronasal fistulas, and bony defects in adolescents born
      with a cleft are safe and reliable when carried out by an experienced cleft
      surgeon and team. They enhance the patient's quality of life and well-being. They
      also provide a stable foundation in which final soft-tissue lip and nose
      revisions may be carried out.

PMID- 9246524
TI  - Secondary cleft deformities.
AB  - Cleft palate fistulas are an unfortunate complication that may follow repair of a
      cleft palate. The presenting symptoms may be variable, and a full evaluation is
      necessary to identify which symptoms are directly attributable to the fistula. A
      multidisciplinary approach is recommended when formulating a treatment plan,
      which takes into consideration symptomatology, speech, growth, dentition,
      aesthetics, and individual medical and psychosocial needs.

PMID- 9246525
TI  - Avoiding pitfalls and managing complications of aesthetic contouring of the
      craniofacial skeleton.
AB  - Contouring of the facial skeleton has become applicable to a wide spectrum of
      patients. Although complications do occur, they now can be managed in a safe and
      predictable fashion. Moreover, it has been our experience that through increased
      use and attention to the tenets described in this article, the incidence of
      postoperative complications is significantly reduced.

PMID- 9246528
TI  - Acute respiratory distress syndrome.
AB  - Acute Respiratory Distress Syndrome (ARDS) occurs in a wide range of adult and
      pediatric critical care settings. This article provides an overview of ARDS
      including the controversies in definition, a summary of pathophysiology,
      diagnosis, clinical presentation, and management options. The article also
      attempts to emphasize new management options in the management of ARDS, and
      highlights differences between adults and children.

PMID- 9246527
TI  - Submersion injuries in children and adults.
AB  - Drowning and near drowning remain a common cause of childhood death and
      disability. Toddlers aged one through four drown in private swimming pools.
      Submersions greater than 10 minutes and lack of CPR at the scene or the need for
      greater than 20 minutes of resuscitation portends a poor prognosis. Management of
      respiratory failure without neurologic impairment has the most successful
      outcome. Prevention of drowning morbidity is dependent on constant parental
      supervision, and immediate and expert CPR.

PMID- 9246526
TI  - Status asthmaticus.
AB  - Despite improved understanding of the pathophysiology and treatment of asthma,
      significant morbidity and mortality exist for both the pediatric and adult
      patient. The critical care practitioner must understand the chronic as well as
      the acute nature of the condition in order to provide effective intervention.
      This article reviews the epidemiology and pathophysiology of asthma, clinical
      assessment, management principles, therapeutic modalities, and future approaches
      to the management of asthma.

PMID- 9246529
TI  - Acute respiratory failure in the HIV-seropositive patient.
AB  - Since approximately 40% to 65% of patients with AIDS will develop pulmonary
      disease, HIV-seropositive patients represent a large cohort of immunosuppressed
      individuals with the potential to progress to respiratory failure requiring
      mechanical ventilation and admission to the intensive care unit. This article
      reviews the cause, pathophysiology, diagnostic approach, and management of acute
      respiratory failure requiring mechanical ventilation in HIV-seropositive
      patients. Prognostic factors and survival rates for episodes of respiratory
      failure are also discussed. In addition, an overview of acute respiratory failure
      in pediatric AIDS patients is presented.

PMID- 9246530
TI  - Septic shock.
AB  - Although our understanding of molecular events in septic shock is growing
      exponentially, bedside management has changed only incrementally over the last 20
      years. In pediatric and adult patients alike, treatment continues to be largely
      supportive. Morbidity and mortality, though gradually improving, continue to be
      high. The major similarities, as well as the minor differences, between pediatric
      and adult septic shock are reviewed in this article, with an emphasis on current
      clinical practice and recent clinical investigations of novel therapies.

PMID- 9246531
TI  - Acute renal failure in infants, children and adults.
AB  - Acute renal failure (ARF) occurs in many critically ill patients regardless of
      age. A combination of events often seen in critical care settings, including
      shock, sepsis, hypoxia, and the use of potentially nephrotoxic medications,
      combine to make ARF an ongoing and important management issue in critical care
      medicine. Since the events leading to the development of ARF differ in infants,
      children, adults, and the elderly, the pathophysiology, clinical features, and
      treatment modalities do indeed have remarkable similarities among the different
      age groups.

PMID- 9246532
TI  - Etiology and treatment of acquired coagulopathies in the critically ill adult and
      child.
AB  - Excessive bleeding frequently complicates the care of critically ill patients.
      Except in the case of trauma or inpatients with known coagulopathies, the
      bleeding is generally not directly related to the illness that results in
      admission to the intensive care unit. In general, the causes of the bleeding can
      be divided into three categories: consumptive coagulopathies, bleeding related to
      "hepatic issues," and iatrogenic causes. In most circumstances, the pathogenesis
      and management of these acquired coagulopathies do not differ between the adult
      and child patient. However, some differences do exist in regards to the clinical
      manifestations and management of some consumptive coagulopathies. This article
      reviews the more common causes of bleeding in the critically ill patient and
      outlines diagnostic and treatment approaches for these patients. Particular
      emphasis will be placed on the differences in presentation and management where
      differences exist.

PMID- 9246533
TI  - Head injuries in children and adults.
AB  - Motor vehicle-related accidents account for the largest number of head injuries
      in all ages. This article reviews types of injury, neurologic assessment,
      secondary injury, brain swelling, seizures, resuscitation, and intensive care.

PMID- 9246534
TI  - Status epilepticus in children and adults.
AB  - Status epilepticus (SE) in children and adults is one of the most common
      neurology problems confronting the intensivist. Recognition of SE is usually
      straightforward, but may be complicated by the effects of other diseases or
      therapies. Emergent treatment is necessary to prevent further brain damage. This
      article reviews protocols for standard treatments of SE patients and includes
      recommendations for the management of refractory SE.

PMID- 9246535
TI  - Poisoning and drug overdose.
AB  - Poisoning is a common cause for intensive care unit admission for both children
      and adults, and most poisoning victims are effectively treated using standard
      decontamination measures and supportive care. For a small number of poisons,
      acceleration of toxin removal with hemodialysis or hemofiltration is indicated.
      Similarly, specific antidotes are indicated in a few selected circumstances.
      Rarely, patients may benefit from more aggressive supportive techniques such as
      cardiopulmonary bypass.

PMID- 9246536
TI  - Common nutritional issues in pediatric and adult critical care medicine.
AB  - This article discusses many of the nutritional topics important to the
      intensivist. Nutritional assessment, substrate immunonutrition, and disease
      specific issues are presented. Early introduction of enteral feeds and the use of
      nutritional modulation are emphasized.

PMID- 9246537
TI  - Ethics in the intensive care unit. Creating an ethical environment.
AB  - This article discusses ethical issues that exist each and every day in
      interactions with patients, families, and fellow workers in the ICU, even in the
      absence of overt conflict or controversy. The creation of an ethical working
      environment in the ICU is a necessary precondition for dealing with the ethical
      issues raised by specific issues such as cardiopulmonary resuscitation, the
      limitation or withdrawal of life-sustaining treatment, the special care of
      children with disabilities, brain death, and organ procurement, and triage. The
      creation of an ethical working environment requires developing a collaborative
      relationship with patients, families, staff, and other health care professionals.

PMID- 9246538
TI  - The biologic and clinical spectrum of Glanzmann's thrombasthenia: implications of
      integrin alpha IIb beta 3 for its pathogenesis.

PMID- 9246539
TI  - The role of Epstein-Barr virus in lymphoid malignancies.

PMID- 9246540
TI  - Stromelysin-3: a paradigm for stroma-derived factors implicated in carcinoma
      progression.

PMID- 9246541
TI  - Controversies regarding screening mammography.

PMID- 9246542
TI  - Rethinking the relationships between disability, rehabilitation, and society.
AB  - This paper provides a critical review of contrasting ways of thinking about the
      nature of disability in society. It highlights the dominance of the medical model
      of disability whereby medical and rehabilitative professionals and practitioners
      tend to conceive of disability as an individual physiological and/or medical
      condition requiring the afflicted individual to be given appropriate medical
      and/or rehabilitative support. As the paper suggests, such perspectives are
      problematical because they reduce the understanding of disability to the
      conditions of the individual 'patient' and ignore wider social and environmental
      influences in engendering a state of disability. Thus, the paper highlights other
      perspectives on disability and society which suggest that social, attitudinal,
      and environmental barriers in society are an important component in disabling
      people with physical and/or mental impairments. In this sense, breaking down
      disabling social practices against people with disabilities might be as
      important, if not more so, than seeking to cure physical and/or mental
      impairments.

PMID- 9246543
TI  - Mobility of persons after traumatic lower limb amputation.
AB  - The objective of this study was to determine the influence of time span since
      amputation on mobility of persons experiencing traumatic lower limb amputation. A
      special questionnaire was sent to such persons and responses were analysed
      statistically. The subjects comprised 223 persons after traumatic lower limb
      amputation, residents of Slovenia. We discovered that 186 (74.2%) are using their
      prosthesis for more than 7 hours per day, 109 (52.2%) are able to walk outdoors
      without crutches, and 129 (57.8%) climb more than 20 stairs per day. In addition,
      those who are walking without crutches, walking longer distances, still cycling
      and driving a care are, on average, 5-10 years younger than the others. However,
      around one-third of persons who were young at the time of amputation face
      limitations of mobility later in life. A total of 76 (35.3%) are able to walk
      only up to 500 m out of doors, 38 (18.2%) can walk only with a pair of crutches,
      62 (29.7%) need a cane or one crutch, and 37 (16.6%) cannot climb stairs. We
      conclude that successful fitting and usage of a prosthesis by persons after lower
      limb amputation promotes independent walking and mobility in everyday life. The
      level of independence achieved is related to time span since amputation.

PMID- 9246544
TI  - Outcome following stroke.
AB  - A community study based on an age-stratified sample of those aged 55 years and
      older in a northern health district in the United Kingdom has been used to
      consider the implications for purchasing health-care services for those who have
      survived a stroke. The study showed that while almost a quarter of those
      reporting a stroke had made a full recovery, a wide range of impairments and
      disabilities persisted. Almost half reported needing help at least daily. A
      logistic regression model to predict this level of dependency found that
      impairments, disabilities and other factors, such as locality, were also
      predictive of dependency. A second model predicting mobility handicap (dwelling
      restricted) was found to have a similar mix of predictors. These results show how
      purchasers must consider the broad outcome in terms of a continuum of impairment,
      disability and handicap. The results also show that handicap is a distinct
      concept that draws together many influences which act upon the individual.

PMID- 9246545
TI  - The true rates of injury among workers in New Zealand: comparing 1986 and 1991.
AB  - This study has established true injury rates in New Zealand in 1986 and 1991 for
      the general and working populations. The general population grew by 3% between
      the two censuses, while the injury rate increased by 23%. The workforce decreased
      by 7% while the workforce injury rate rose by 11%. The numbers of salary earners
      and wage earners fell by 10% and the number of self-employed workers rose by 4%,
      the injury rates in the former rising by 16% and falling by 7% in the latter
      group. This suggests either a lower injury rate or a lower claim rate among these
      latter workers. Young males have the highest injury rates in the general and
      workforce population. Women have half the injury rate of men, suggesting that
      women should pay lower insurance premiums. Detailed analysis revealed 'high
      injury rate/high cost' groups in whom targeted intervention strategies should be
      cost-effective. This study gives a baseline against which changes can be
      measured. We recommend that this study be repeated.

PMID- 9246546
TI  - Work environment of blind computer specialists in Japan.
AB  - This study aimed at investigating the circumstances in the workplace of computer
      specialists with visual impairment in Japan through telephone interviews. The
      results indicate that developments in assistive technology and personal support
      for blind computer specialists are insufficient, due to the complexity of the
      Japanese language. In particular the spread of graphical user interface is
      threatening to blind specialists. Although assistive technology and personal
      assistance are indispensable for the blind to read or create printed documents,
      this environment has not been appropriately prepared at this time. The
      opportunity of retraining and providing new information to the blind specialists,
      in addition to providing funds and personal services, are necessary for
      implementing their jobs.

PMID- 9246547
TI  - Rehabilitation following a stroke: a participant perspective.
AB  - Following a stroke in January 1996 the author, a college lecturer, kept notes of
      his feelings, perceived treatment, and other people's responses to him. This
      paper reports these especially as they relate to the experience of illness,
      disability and rehabilitation. Areas covered include the experience of the stroke
      itself, perceptions of the process, reactions to disability and therapies, and
      the experience of trying to return to a 'normal' life. No claim is made for the
      uniqueness or significance of this account. It is simply offered as a
      contribution towards a better understanding of the patient's perspective on
      disability and rehabilitation.

PMID- 9246548
TI  - Traumatic events and post-traumatic stress disorder in cocaine users entering
      private treatment.
AB  - We investigated traumatic events, post-traumatic stress disorder (PTSD), and
      psychiatric comorbidity in 450 men and women entering private, hospital-based
      treatments for cocaine dependence. Overall prevalence of event exposure was the
      same for women and men; however, women were approximately five times more likely
      than men to be diagnosed with lifetime and current PTSD. Women experienced more
      PTSD than men even when exposed to the same type of event. In most subjects with
      PTSD, onset of the disorder preceded onset of cocaine dependence. Subjects with
      PTSD were more likely than those without PTSD to have additional co-occurring
      mental disorders. Findings from this relatively affluent, privately treated
      sample suggest that PTSD and cocaine dependence are related, independent of
      patients' resources. They further indicate that the relationship between gender
      and PTSD is robust across patient populations. More complex examinations of PTSD,
      cocaine dependence, and gender are needed to better understand these
      relationships and to design effective interventions.

PMID- 9246549
TI  - Knowledge and experience of drug use amongst church affiliated young people.
AB  - A large and growing proportion of young people in the UK are using drugs.
      Research from the US suggests a protective effect of church affiliation or
      'religiosity', but this has not been investigated in British young people. In the
      present study, the prevalence of drug use was estimated amongst 7666 church
      affiliated young people in the UK in 1995, using a self report questionnaire
      survey. In the 12-16 year old age group, 23.4% had been offered at least one of a
      list of drugs, and 9.7% had tried such drugs. In those aged 17-30 years the
      figures were 46.1% and 23.3%, respectively. These figures are perhaps slightly
      less than, those obtained in secular surveys. Those who gave more positive
      responses to questions on Christian commitment were less likely to have been
      offered any of the listed drugs, or to have used them, as compared with those who
      gave no such responses. A lifetime history of ever having smoked demonstrated a
      far stronger association, with smokers being 15-20 times more likely to have used
      one of the listed drugs.

PMID- 9246550
TI  - Tolerance and cross tolerance to the accuracy- and rate-decreasing effects of mu
      opioids in rats responding under a fixed-consecutive-number schedule.
AB  - The purpose of the present investigation was to examine the development of
      tolerance to the effects of morphine and other mu opioids in rats responding
      under a fixed-consecutive-number (FCN) schedule of food presentation. To this
      end, five rats were trained under an FCN schedule and subsequently tested with a
      variety of mu opioids both before and during chronic exposure to a 0.4 mg/ml
      morphine drinking solution. Morphine, fentanyl, buprenorphine, butorphanol and
      nalbuphine produced dose-dependent decreases in both accuracy and response rate
      when tested prior to the chronic regimen. In most instances, doses of these drugs
      that decreased accuracy also decreased response rate. During chronic treatment,
      tolerance developed to the effects of morphine and cross-tolerance was conferred
      to the effects of fentanyl, buprenorphine and butorphanol. A greater degree of
      tolerance was conferred to the effects of butorphanol than to the other opioids
      examined, and the degree of tolerance conferred to butorphanol's rate-decreasing
      effects was greater than the degree of tolerance conferred to its accuracy
      decreasing effects. Doses of naloxone that had no effect prior to morphine
      treatment produced large decreases in accuracy and response rate when tested
      during the chronic regimen. In contrast to the other opioids examined, the
      potency of nalbuphine was not altered by chronic morphine administration. These
      data emphasize the importance of both pharmacological and procedural variables in
      the development of tolerance and cross tolerance to the behavioral effects of
      opioids.

PMID- 9246551
TI  - Intracranial self-stimulation in female and male rats: no sex differences using a
      rate-independent procedure.
AB  - Given gender differences in human drug use and dependence, this study examined
      sex differences in reinforcement processes that may underlie such behavior. A
      psychophysical determination of reinforcement threshold was made using an
      intracranial self-stimulation (ICSS) paradigm, electrically activating the medial
      forebrain bundle (MFB) as it passes through the lateral hypothalamus (LH). Using
      this response rate-independent procedure, basal reinforcement thresholds were not
      significantly different in male vs. female rats (119.4 +/- 3.3 microA vs. 110.8
      +/- 4.0 microA, respectively; N = 8/sex). Further, baseline reinforcement
      threshold did not fluctuate systematically across stages of the estrous cycle in
      female rats. The psychostimulants D-amphetamine (0.056-0.56 mg/kg s.c.) and
      cocaine (1.8-18.0 mg/kg i.p.) dose-dependently lowered reinforcement threshold,
      with no significant sex difference. The opioid morphine (0.56-5.6 mg/kg s.c.) did
      not significantly lower reinforcement threshold in either sex. These results
      contrast those of some previous studies that have used response rate-dependent
      measures of reinforcement threshold; procedures which are less rate-dependent may
      be more appropriate when examining subject variables such as sex and stage of
      estrous.

PMID- 9246552
TI  - Changes in network characteristics and HIV risk behavior among injection drug
      users.
AB  - Studies indicate that HIV risk behaviors vary greatly among injection drug users
      (IDUs). The source of such variation is often ascribed to individual differences,
      but much of it is due to how IDUs are grouped into social networks. Nevertheless,
      given the turbulent and uncertain lives led by many IDUs, it would not be
      surprising if their social networks changed substantially over time. We used data
      from a study of the social networks of IDUs in Chicago and Washington, DC, to
      examine changes in individual behavior and network characteristics over time. The
      results indicated few changes in standard network measures, such as density of
      ties or network size, over time. However, specific network change measures, that
      is, indicators of movement into and out of networks, showed significant movement
      of network members over time. Moreover, movement of members into a network
      significantly predicted a higher likelihood of risky injection drug use over
      time. We suggest that these movements are indicative of a lack of a stable
      resource base among IDU networks.

PMID- 9246553
TI  - Relationships between frequency and quantity of marijuana use and last year proxy
      dependence among adolescents and adults in the United States.
AB  - The association between levels of marijuana use and last year dependence is
      investigated in a nationally representative sample of adolescents and adults, who
      used marijuana within the last year (n = 9284). Data are aggregated from three
      surveys (1991-1993) of the National Household Survey on Drug Abuse. A proxy
      measure of DSM-IV dependence criteria was developed from self-reported symptoms
      of dependence and drug-related problems. Both frequency and quantity of marijuana
      use within the last year are linearly associated with the logit of the
      probability of being dependent on marijuana. The associations vary significantly
      by age but not gender. Adolescents are dependent at a lower frequency and
      quantity of use than adults: the differences diverge as level of use increases.
      Twice as many adolescents as adults who used marijuana near-daily or daily within
      the last year were identified as being dependent (35% versus 18%). Frequency and
      quantity of use each retained a unique effect on dependence, but frequency
      appeared to be more important than quantity in predicting last year dependence.
      These results provide insight into the processes underlying the age and sex
      differentials observed in the prevalence of marijuana dependence. The
      implications of the findings for the epidemiology of marijuana use and dependence
      are discussed.

PMID- 9246554
TI  - Comorbidity of drug dependence and other mental disorders: a two-phase study of
      prevalence at outpatient treatment centres in Italy.
AB  - A cross-sectional multicentre study aimed at evaluating the prevalence of DSM III
      R Axis I morbidity among drug addicts seeking treatment. Consecutive outpatients
      of the National Health Service's treatment units (aged 18-60 years, fulfilling
      criteria for drug dependence and without primary diagnosis of alcohol dependence)
      were enrolled at intake. In the first phase of the study, professional staff
      members evaluated current psychiatric morbidity of 317 clients clinically. In the
      second phase, trained interviewers administered the Composite International
      Diagnostic Interview and a European adaptation of the Addiction Severity Index to
      65 probands. Some current psychiatric morbidity was found in 26.2% of subjects
      recruited during the first phase and in 22.2% during the second; lifetime
      comorbidity was ascertained in 32.3% of probands recruited in the second phase.
      Unfortunately, remarkable rates of undetermined diagnostic assessment during the
      second phase are due to refusers. The distribution of categorical diagnoses is
      somewhat different between the two samples, but the most frequent are Anxiety and
      Mood disorders in both. Primary versus secondary psychiatric diagnoses were also
      distinguished when evaluated over a lifetime. The rates of psychiatric
      comorbidity are low in this study as compared with previous investigations, but
      suffer from a poor compliance with structured diagnostic procedures by unselected
      probands. Other methodological factors may also affect this kind of research.
      Prospective studies are needed to evaluate the validity of comorbid diagnostic
      constructs and their prognostic significance. Also a concurrent assessment of
      Axis II disorders may be helpful to explain symptomatic polymorphism in case of
      multiple Axis I comorbidity.

PMID- 9246555
TI  - A cocaine-positive baseline urine predicts outpatient treatment attrition and
      failure to attain initial abstinence.
AB  - The primary study objective was to ascertain whether a prior finding that the
      baseline cocaine urine toxicology predicted treatment dropout for cocaine
      dependent outpatients could be extended to three additional cocaine dependent
      outpatient treatment samples and whether the urine toxicology also predicted
      attainment of initial abstinence for the four samples. A secondary objective was
      to ascertain the extent to which other baseline variables accounted for
      additional outcome variance over and above that afforded by urine toxicology. To
      evaluate the first objective, the relationships between the baseline cocaine
      urine and each of two measures of within treatment response--the completion of
      treatment or the attainment of initial abstinence--were determined for each of
      the treatment samples. The second objective was evaluated by a stepwise,
      hierarchical logistic regression analysis, with the urine toxicology entered in
      the first step, baseline Addiction Severity Index (ASI) variables in the second
      step, and achievement of initial abstinence as the outcome. In all four samples,
      patients with a urine indicative of recent cocaine use were less than half as
      likely to complete treatment or achieve initial abstinence. Individual ASI
      baseline variables did not contribute statistically significant variance over and
      above that predicted by the cocaine urine toxicology. The findings confirm the
      utility of the initial cocaine urine as a predictor of unfavorable outpatient
      treatment response.

PMID- 9246556
TI  - Quantitative electroencephalographic differences associated with alcohol,
      cocaine, heroin and dual-substance dependence.
AB  - Resting electroencephalographic (EEG) activity was evaluated in 88 drug-dependent
      inpatients, abstinent 1-6 months, and 14 non-drug-dependent controls. The
      patients were assigned to one of four groups using DSM-III-R criteria: alcohol
      dependent (n = 12), cocaine-dependent (n = 21), heroin-dependent (n = 19), or
      dual alcohol- and cocaine-dependent (n = 36). The analysis revealed significant
      differences between the five subject groups in high- and low-frequency beta
      power, but not in other frequency bands. Beta power was significantly greater in
      the alcohol-dependent and cocaine-dependent groups relative to non-drug-dependent
      controls. These group differences did not correlate with quantity/frequency
      measures of alcohol or cocaine use, family history, personality, mood, or
      demographic characteristics. The similar increases in EEG beta found in alcohol-
      and cocaine-dependent patients do not suggest a direct drug effect. Rather, they
      suggest the existence of a common premorbid variable or a complex interaction
      between alcohol/drug use and other variables.

PMID- 9246557
TI  - Subjects with a history of drug dependence are more aggressive than subjects with
      no drug use history.
AB  - Aggressive responding was compared between 29 subjects with a history of
      substance dependence and 24 subjects with no drug use history, using the Point
      Subtraction Aggression Paradigm. The hypothesis was that subjects from the
      substance dependence history group would emit more aggressive responses than
      subjects with no drug use history. The substance dependence history group emitted
      more aggressive responses per session than the non drug using group (F(1,49) =
      14.867, P = 0.032). These results are consistent with previous studies that have
      reported an association between aggression and drug abuse or dependence.

PMID- 9246558
TI  - Amphetamine-related harms and treatment preferences of regular amphetamine users
      in Sydney, Australia.
AB  - Amphetamines remain a popular illicit drug among young adults in Australia and a
      number of other countries, particularly by injection. A significant increase in
      the number of people presenting to drug treatment services with a primary
      amphetamine problem in Australia and the US has occurred in recent years. A
      survey of 200 regular amphetamine users was conducted in Sydney to determine the
      treatment issues and preferences of this population. Substantial harm associated
      with the use of this drug was found, most notably psychological problems,
      physical health problems, dependence and financial problems. A perceived need for
      amphetamine-specific treatment was evident. Popular treatment options requested
      by users included pharmacotherapies, natural therapies and counselling. While
      regular amphetamine users can attend existing treatment services, the efficacy of
      these treatments for amphetamine problems has not been evaluated. There is also a
      need to develop and evaluate amphetamine-specific interventions in order to
      attract this population into treatment.

PMID- 9246559
TI  - How constant is an individual's route of heroin administration? Data from
      treatment and non-treatment samples.
AB  - Three routes of heroin use were identified--injecting, 'chasing the dragon' and
      snorting. Whilst injecting and 'chasing the dragon' accounted for virtually all
      current heroin use, snorting had been the first route of use for nearly a fifth
      of heroin users in both the treatment and community samples. Overlap of lifetime
      experience of the different routes was widespread, with the majority of heroin
      users in both the treatment and community samples having used heroin by more than
      one route. Although less than half of the treatment sample had used heroin by
      injection on the first occasion, more than 90% had injected at least once, and
      over 80% had at some time used by 'chasing the dragon'. Only a quarter of the
      community sample had first used heroin by injecting, and yet, by the time of
      interview, two-thirds of the sample had injected. The majority of durable changes
      in route of heroin use were towards injecting and 'chasing the dragon', with
      transitions to snorting being extremely rare. For both the samples, transitions
      to injecting were twice as frequent as transitions to 'chasing'. Snorting
      appeared to be an unstable route of use, with almost all who initially snorted
      their heroin now using by injecting or 'chasing the dragon'.

PMID- 9246560
TI  - Serum and intracellular magnesium concentrations in intoxicated chronic alcoholic
      and control subjects.
AB  - Serum magnesium levels may not accurately reflect overall magnesium homeostasis.
      To clarify the relationship between serum and intracellular magnesium
      concentrations in chronic alcoholism, we determined intralymphocytic magnesium
      levels and serum magnesium, sodium and potassium concentrations in ten chronic
      alcoholic subjects admitted to the emergency room during acute ethanol
      intoxication, and compared the results to those of 14 healthy nonalcoholic
      controls. Serum magnesium, sodium and potassium concentrations were within the
      normal range in both groups of subjects and determination of intralymphocytic
      magnesium levels revealed a nonsignificant decrease in alcoholic subjects
      compared to controls. In conclusion, serum and intralymphocytic magnesium
      concentrations did not differ between chronic alcoholics and controls in our
      population; the results of the present study do not support the practice of
      routine magnesium administration to chronic alcoholics in the emergency room
      setting.

PMID- 9246561
TI  - Separation method of IgG fragments using protein L.
AB  - Protein L (IgG kappa-chain-binding bacterial protein) showed a precipitate
      line(pseudo-immuno-reaction) with IgG and F(ab')2 fragment, but did not show any
      line with the Fab fragment, the Fc fragment and free kappa-chains in the micro
      Ouchterlony method. The IgG and Fab fraction obtained from pa-pain-digested IgG
      (from the sera of patients with chronic thyroiditis), followed by Protein A
      Sepharose, were separated by Protein L-Sepharose affinity chromatography. The
      unbound fraction (UF) consisted of IgG(lambda) or Fab(lambda) and the bound
      fraction (BF) consisted of IgG(kappa) or Fab(kappa) were obtained. Anti
      thyroglobulin and anti-thyroid peroxidase antibody activities were found equally
      in both the UF and the BF. When Fab(kappa) was reduced with dithiothreitol (DTT),
      the Fd fragment in the UF could be separated from the free kappa-chain and the
      unreduced Fab(kappa) in the BF with a Protein L-Sepharose column. A separation
      method of human IgG fragments such as free kappa-chain, combined forms of kappa
      chain [Fab or F(ab')2], and the Fd region, using Protein L, is described.

PMID- 9246562
TI  - C5b-7 and C5b-8 precursors of the membrane attack complex (C5b-9) are effective
      killers of E. coli J5 during serum incubation.
AB  - The finding that C9-deficient sera (C9D) can kill serum sensitive strains of Gram
      negative bacteria by us and other investigators, questions the role of C9 in the
      membrane attack complex as necessary for cell death. In these studies we have
      demonstrated that C5b-8 complexes generated on E. coli J5 during incubation in C9
      depleted and C9-neutralized sera are effective in killing Gram-negative bacteria.
      In the same study, we extended our investigations to show that the deposition of
      C5b-7 complexes (from C8-deficient [C8D], C8 depleted and C8-neutralized sera) is
      also effective in killing Gram-negative bacteria. In all cases, these studies
      demonstrated that when E. coli J5 was incubated with C8D, C9D and pooled normal
      human serum [PNHS], deposited C5b-9 complexes from PNHS produced more killing
      than C5b-7 or C5b-8 complexes alone. These experiments clearly demonstrated that
      C5b-7 and C5b-8 complexes are bactericidal and that multimeric C9 within C5b-9 is
      not an absolute requirement for inner membrane damage and cell death of Gram
      negative bacteria.

PMID- 9246563
TI  - Impact of a truncated invariant chain on in vitro assembly of class II MHC
      molecules depends on the affinity of invariant chain for a given alpha beta
      dimer.
AB  - The assembly of major histocompatibility complex (MHC) class II alpha and beta
      chains occurs in the endoplasmic reticulum (ER) with the involvement of MHC class
      II-associated invariant chain (Ii). The present study investigated the impact of
      Ii on the assembly of both I-A haplotype-matched and -mismatched alpha and beta
      chains using an in vitro translation system. The alpha and beta chains of I-Ab, I
      Ad and I-Ak were cotranslated in vitro in different combinations with or without
      cotranslation of a truncated murine Ii (mIi 1-131). The translated products were
      sequentially immunoprecipitated, first with conformation-dependent monoclonal
      antibodies, then with conformation-independent antibodies. The results show: (1),
      Ii did not associate with free A alpha and free A beta chains; (2), mIi 1-131
      significantly augmented the amount of properly assembled A alpha b A beta b, A
      alpha b A beta d, A alpha b A beta k and A alpha k A beta b dimers, but had
      little affect on the assembly of A alpha d A beta d, A alpha k A beta k, A alpha
      d A beta b, A alpha k A beta d and A alpha d A beta k; (3), All A alpha A beta
      dimers whose assembly could be significantly facilitated by mIi 1-131 could be
      coimmunoprecipitated along with substantial amounts of mIi 1-131. This finding is
      consistent with prior observations that the impact of Ii on class II molecule
      assembly is allele specific. Furthermore, these results suggest that the
      efficient assembly of alpha and beta chains is primarily determined by the
      affinity between alpha and beta chains and the the high affinity of mIi for A
      alpha A beta dimers is required for mIi 1-131 to assist proper A alpha A beta
      assembly, most probably through a mechanism in which Ii stabilizes properly
      assembled A alpha A beta dimers or promotes folding of associated alpha and beta
      chains to help achieve a stable dimer state.

PMID- 9246564
TI  - Increase of eosinophilic cell population in bone marrow of rats by immunization
      with Ascaris suum antigen.
AB  - Immunization of rats with the antigen, Ascaris suum extract, increased the number
      of peripheral eosinophils. Analysis by Western blot and reverse transcription
      polymerase chain reaction revealed that the levels of major basic protein and its
      mRNA in the bone marrow were also increased, suggesting that eosinophilic cell
      population in the bone marrow is increased by the immunization. These findings
      indicate that immunization with this antigen stimulates differentiation of
      progenitor cells to eosinophils in the bone marrow, and induces blood
      eosinophilia.

PMID- 9246565
TI  - Different stabilities of the N- and C- terminal domains of human interferon
      alpha.
AB  - The present results are consistent with the hypothesis predicting two
      structurally independent polypeptide domains in the regions 1-92 and 111-166 of
      the type I IFNs. However, we observed differences in molecular unfolding between
      the N- and C-terminal portions of human IFN-alpha during denaturation in SDS
      solutions. Monoclonal antibodies (mAbs) detected changes in the N-terminal region
      (residues 1-85) of denaturated IFN-alpha 1 or IFN-alpha 2. In contrast, SDS
      denaturation of antigens did not affect the reactivity of mAbs with epitopes
      located in the C-terminal portion (residues 105-166) of both IFNs. The N-terminal
      domain is known to be involved in the high affinity receptor binding of IFN
      alpha. Therefore a theory that the active sites may be conformationally more
      flexible than the rest of the polypeptide might explain the lower conformational
      stability of this domain.

PMID- 9246566
TI  - Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in
      naive T cells.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is a cytokine with complex
      immunomodulatory effects including the ability to inhibit the onset or severity
      of autoimmune disease. This study was designed to test the possibility that one
      mechanism by which TGF-beta 1 exerts its immunosuppressive effects is by inducing
      antigen (Ag)-specific unresponsiveness in CD4+ cells. TGF-beta 1 was shown here
      to inhibit the Ag-specific proliferation of naive CD4+ cells from T cell receptor
      (TCR) transgenic mice. More importantly, the naive CD4+ cells exposed to TGF-beta
      1 and Ag, but not to TGF-beta 1 alone, in primary cultures were unable to
      proliferate or secrete IL-2 in response to a subsequent Ag challenge following
      removal of TGF-beta 1 from the cultures. Anti-CD28 mAb partially blocked the Ag
      specific inactivation induced by TGF-beta 1 in naive CD4+ cells. The inhibitory
      effects of TGF-beta 1 on CD4+ cells are not mediated by alterations in APC
      costimulation since TGF-beta 1 did not inhibit the Ag-induced expression of MHC
      class II molecules, CD80 or CD86 on splenic APC. Taken together, the results
      suggest that the immunosuppressive activities of TGF-beta 1 encompass direct
      induction of Ag-specific unresponsiveness in naive CD4+ cells.

PMID- 9246567
TI  - Intersite helper function of T cells specific for a protein epitope that is not
      recognized by antibodies.
AB  - Humoral responses to a protein require T-B cell communication for B cell
      activation by T cells. Previous studies from this laboratory have mapped the T
      and B cell recognition sites (epitopes) on sperm-whale myoglobin (Mb) and several
      other proteins. It was found that, five of six regions on Mb recognized by T
      cells are also recognized by B cells (i.e. antibodies). There is, however, one
      region (E6) residing within Mb residues 61-77, that is recognized only by T cells
      and to which no antibody (Ab) responses are detectable. To investigate the
      function of this exclusive T cell epitope, we established, from E6-primed BALB/c
      mice, an E6-specific T cell line (T(e6)) which comprised Th2-type cells. These T
      cells provided help in vitro to B cells from Mb-primed BALB/c mice and activated
      them to produce anti-Mb Abs of the IgM (58.2%) and IgG (41.8%) isotypes. The
      helper activity of T(e6) cells was dependent on the concentration of the
      challenging Ag (intact Mb or peptide E6) in culture. Action of soluble factors
      released from E6-activated T(e6) cells on B(mb) cells led to low production of
      anti-Mb Abs, suggesting that activation of the B cells was more dependent on
      their contact with T cells. Mapping of the epitope recognition of the anti-Mb Abs
      produced in vitro by B(mb) cells on activation by T(e6) revealed that this
      activation was not general to all antigenic regions recognized by anti-Mb Abs in
      BALB/c mice. E6-specific T cells caused in vitro activation and differentiation
      of B(mb) cells into plasma cells that secreted anti-Mb Abs directed, in
      decreasing order, against the following Mb regions: E4 (107-120) > E3 (87 - 100)
      > E1 (10 - 22). Little or no Ab responses could be detected against peptides E2
      (50 - 62), E5 (141 - 153) and E6 (61 - 77). With B cells of peptide-primed BALB/c
      mice, T(e6) cells activated strongly E4-, E3- or E1, and only very slightly E2-
      or E6-, primed B cells to secrete Abs against the correlate peptide, but failed
      completely to activate E5-primed B cells. The results show that a protein T cell
      epitope, to which no Abs are detectable, plays an active role in B cell responses
      against other epitopes within the same protein.

PMID- 9246568
TI  - Localization of the regions on the C-terminal domain of the heavy chain of
      botulinum A recognized by T lymphocytes and by antibodies after immunization of
      mice with pentavalent toxoid.
AB  - We have mapped the regions recognized by T and/or B cells (Abs) on the C-terminal
      domain (Hc) of the heavy chain of botulinum neurotoxin serotype A (BoNT/A) after
      immunization of two inbred mouse strains with pentavalent toxoid (BoNTs A, B, C,
      D and E). Using a set of synthetic overlapping peptides, encompassing the entire
      Hc domain (residues 855-1296), we demonstrated that T cells of Balb/c (H-2d)
      mice, primed with one injection of toxoid, recognized two major regions within
      residues 897-915 and 939-957. After multiple inoculations with toxoid, T cells of
      Balb/c expanded their recognition ability and responded very well to challenge
      with peptide 1261-1279 and moderately to stimulation with peptide 1149-1167.
      Unlike Balb/c T cells, those of toxoid-primed SJL (H-2s) mice exhibited a more
      complex profile and responded to challenge with a large number of overlapping
      peptides. After one toxoid injection, however, three peptides, 897-915, 939
      957/953-971 overlap and 1051-1069, were the most potent T cells stimulators.
      After three toxoid injections, peptides 897-915 and 1051-1069 remained
      immunodominant while the third region was shifted upstream to 925-943/939-957
      overlap. The immunodominant epitope within peptide 897-915 was recognized
      exclusively by T cells, since no Abs were detected against this region. The Ab
      binding profiles of the two mouse strains were quite similar, showing only small
      quantitative differences. Both, Balb/c and SJL anti-toxoid Abs displayed strong
      binding mainly to peptide 1177-1195, followed by peptides 869-887/883-901 overlap
      and 1275-1296. In addition, a significant amount of Balb/c anti-toxoid Abs was
      bound to peptide 1135-1153. Unlike Balb/c Abs, that interacted weakly with
      peptides 995-1013 and 1051-1069, the anti-toxoid Abs of SJL mice exhibited strong
      binding toward both peptides. The results showed that, in a given strain, the
      regions recognized by anti-toxoid Abs and T cells may coincide or may be uniquely
      B or T cell determinants.

PMID- 9246569
TI  - Does silicone in any form have adjuvancy potential.

PMID- 9246570
TI  - Role of T-lymphocytes in the resolution of endotoxin-induced lung injury.
AB  - An acute neutrophilic lung injury was compared in Balb/c normal and nu/nu (nude)
      mice to assess the role of T lymphocytes in the resolution of acute pulmonary
      neutrophilic inflammation following the administration of endotoxin. Maximal
      neutrophilic infiltration occurred on day 1 post-endotoxin treatment and declined
      to near normal levels by day 5. In contrast, the percentage of lymphocytes in the
      bronchoalveolar lavage (BAL) fluid increased from 1.8% on day 1 post-endotoxin to
      greater than 11% on days three and five, during which time neutrophil resolution
      was occurring. On days 1-5 after endotoxin administration, approximately 40% of
      the CD4 lymphocytes expressed the cell surface activation marker, CD69. Despite
      being CD69+, CD4 cells did not express the high affinity IL-2 receptor chain,
      CD25, to any significant extent on any of the days studied. To assess the
      contribution of T cells to the rate of clearance of neutrophils from the BAL,
      normal and nude Balb/c mice were compared for the percentage of neutrophils
      following nasal administration of endotoxin. Endotoxin-treated nude mice did not
      demonstrate significant differences in either the total white blood cell counts
      or in the clearance of neutrophils from the BAL, as compared to normal Balb/c
      mice. These data indicate that the influx of activated T cells during the
      resolution of neutrophilic pneumonitis does not contribute to the rate of
      neutrophil clearance during acute lung injury.

PMID- 9246571
TI  - Bradykinin antagonizes the effects of alpha-thrombin.
AB  - alpha-Thrombin (AT) and bradykinin (BK) are endogenous mediators that are
      released during an inflammatory response, and could have a synergistic effect on
      endothelial permeability. Human umbilical vein endothelial cells (HUVEC) were
      grown on Transwell membranes and then tested for alterations in permeability to
      fluorescein isothiocyanate-labeled human serum albumin. Addition of 1 microM AT
      produced a significant increase in the permeability coefficient at 30 minutes
      from control levels of 1.59 x 10(-6) cm/sec to 4.92 x 10(-6) cm/sec. BK (1
      microM) produced a similar increase to 4.46 x 10(-6) cm/sec. For both compounds,
      permeability remained elevated for 90 minutes. Pre-treatment of the HUVEC with
      the bradykinin receptor antagonist, Na-adamantaneacetyl-bradykinin (NA-BK) (1
      microM), prior to addition of AT, reduced the AT permeability coefficient to 2.69
      x 10(-6) cm/sec. Addition of NA-BK (1 microM) for 5 minutes, then BK (1 microM)
      for 5 minutes, inhibited the effect of BK and of AT (1 microM on permeability,
      decreasing the permeability coefficient of the endothelial monolayer to control
      levels (1.62 x 10(-6) cm/sec). AT (1 microM) increased HUVEC intracellular
      calcium mobilization, as monitored by FURA-2, to 245 nM from control (70 nM),
      however, pre-treatment with either BK or the bradykinin receptor antagonist
      decreased the AT induced intracellular calcium mobilization compared to AT alone.
      Pre-treatment of the HUVEC with bradykinin (1 microM) for 2 minutes also
      inhibited the effects of alpha-thrombin (1 microM) on f-actin distribution
      examined by BODIPY-phallodin staining and increased the clotting times for an
      alpha-thrombin dependent fibrinogen to fibrin clotting assay. However, incubation
      of bradykinin (1 microM) with alpha-thrombin (1 microM) for either 10 minutes or
      100 minutes produced no detectable hydrolysis products. These data strongly
      suggest that the inflammatory mediators alpha-thrombin and bradykinin when
      released together, rather than being synergistic, are antagonistic.

PMID- 9246572
TI  - Suppression of adjuvant arthritis and synovial macrophage inducible nitric oxide
      by N-iminoethyl-L-ornithine, a nitric oxide synthase inhibitor.
AB  - Nitric oxide (NO.) is a pro-inflammatory effector molecule in certain
      inflammatory diseases, including arthritis. We investigated the production of NO.
      by adjuvant arthritis (AA) synovial macrophages, and studied the effects of a NO.
      synthase inhibitor. N-iminoethyl-L-ornithine (L-NIO). Compared to control rats,
      rats treated with L-NIO in vivo exhibited significantly lower articular index (p
      < 0.05), paw volume (p < 0.05), and synovial fluid cell count (p < 0.05). No
      effect on cutaneous delayed-type hypersensitivity to the disease-initiating
      antigen was observed. Inducible NO. synthase (iNOS) was detected in AA synovial
      macrophages, and cultured AA synovial macrophage iNOS levels were increased by a
      factor of 138 +/- 17% (p < 0.01) by 1 microgram/ml LPS in vitro. Constitutive NO.
      production by AA synovial macrophages (43 +/- 1 nmol/10(5) cells/24 h) was
      significantly inhibited by 10 nM L-NIO in vitro (32 +/- 0.5, p < 0.01). NO.
      production induced by 1 microgram/ml LPS (48 +/- 2) was also decreased by L-NIO
      (39 +/- 2, p < 0.05). In vivo L-NIO treatment also inhibited alveolar macrophage
      NO. production (p < 0.05). The ability of L-NIO to decrease iNOS-mediated
      synovial macrophage NO. production and inhibit the clinical parameters of AA
      implicate macrophage-derived NO. in the pathogenesis of this disease.

PMID- 9246573
TI  - Soluble selectins and ICAM-1 modulate neutrophil-endothelial adhesion and
      diapedesis in vitro.
AB  - We observed that normal plasma dramatically reduces neutrophil-endothelial
      adhesion. Therefore, we identified factors in plasma which might limit PMN
      adhesion in vitro. We found that the anti-adhesive effect was not mediated by
      vasoactive lipids present in plasma. Immunoprecipitation of soluble adhesion
      molecules, P and E-selectins and ICAM-1 restored PMN adhesion to control values.
      We further examined whether soluble adhesion molecules in plasma might also
      regulate PMN endothelial migration in response to fMLP (10(-6) M). Plasma
      significantly reduced PMN migration, and this effect was prevented only by the
      simultaneous removal of soluble P and E selectins and ICAM-1 together, but not
      individually. These data show that soluble selectins and ICAM-1 may regulate PMN
      adhesion and diapedesis, and that alterations in the levels of these molecules
      may regulate PMN-endothelial interactions in vivo.

PMID- 9246574
TI  - Neutrophil chemotactic activity and C5a following systemic activation of
      complement in rats.
AB  - Using ELISA analysis, rat C5a was stimulated in serum from rats undergoing
      systemic activation of complement after intravenous infusion of purified cobra
      venom factor (CVF). Biological (neutrophil chemotactic) activity was also
      assessed. Serum levels of C5a were directly proportional to the amount of CVF
      infused. C5a and neutrophil chemotactic activity, peaked by 5 min, then
      plateaued. In vitro addition of anti-C5a to serum samples of CVF-infused rats
      totally abolished chemotactic activity, indicating that all biological activity
      could be ascribed to C5a. Blood neutrophils obtained from CVF-infused animals
      showed a significant upregulation of CD11b, the increase being reduced (38%) in
      animals pretreated with anti-C5a. These findings indicate that infusion of CVF
      into rats produces generation of C5a, all chemotactic activity in serum being
      related to C5a. The in vivo generation of C5a is, at least inpart, responsible
      for upregulation of CD11b on blood neutrophils.

PMID- 9246575
TI  - Steady-state effects of vitronectin and fibronectin on the binding, uptake, and
      degradation of Pneumocystis carinii in rat alveolar macrophages.
AB  - Pneumocystis carinii pneumonia remains a serious complication of
      immunodeficiency. Vitronectin (VN) and fibronectin (FN) accumulate in the lung
      during P. carinii infection and bind to the organism, thereby enhancing
      macrophage release of TNF alpha. It is not known whether VN and FN also regulate
      uptake and degradation of P. carinii by macrophage when present in concentrations
      similar to those in the lung during pneumonia. To address this, macrophages were
      cultured with 35S-radiolabeled P. carinii and organism binding, phagocytosis, and
      degradation determined in media alone (control), or in the presence of VN or FN
      (100 micrograms/ml each). Soluble VN and FN, in concentrations similar to those
      in the host, did not significantly affect binding uptake or degradation of P.
      carinii by alveolar macrophages. Thus, although VN and FN enhance macrophage
      activation during P. carinii pneumonia, phagocytosis of the organism is not
      increased by these host glycoproteins under steady-state conditions.

PMID- 9246576
TI  - Flavonoids as phospholipase A2 inhibitors: importance of their structure for
      selective inhibition of group II phospholipase A2.
AB  - The inhibitory effect of the plant flavonoid, rutin, on group I phospholipase A2
      (PLA2-I) from porcine pancreas and Naja naja, and on group II phospholipase A2
      (PLA2-II) from Vipera russelli and Crotalus atrox was investigated. Rutin
      efficiently inhibited PLA2-II from both Vipera russelli and Crotalus atrox but
      was only a weak inhibitor of PLA2-I from porcine pancreas and Naja naja. The lack
      of strong inhibition of pancreatic PLA2-I was not due to contaminating proteins
      in the enzyme preparation, since the same weak inhibition was obtained against
      pancreatic PLA2 purified to homogeneity as judged by two-dimensional gel
      electrophoresis. Rutin also efficiently inhibited human PLA2-II from synovial
      fluid but was only a weak inhibitor of human PLA2-I from pancreatic juice,
      suggesting that rutin is a selective PLA2-I from porcine pancreas. The results
      obtained indicate that the hydroxyl group in 5-position as well as the double
      bond and the double-bonded oxygen in the oxane ring are all important for the
      overall ability of flavonoids to inhibit PLA2 activity, and that the hydroxyl
      groups in 3'- and 4'- position are required for selective inhibition of PLA2-II.

PMID- 9246578
TI  - Acute and chronic pain. Preface.

PMID- 9246579
TI  - Neurobiology of pain.

PMID- 9246577
TI  - Effect of topically applied cyclosporin A on arachidonic acid (AA)- and
      tetradecanoylphorbol acetate (TPA)-induced dermal inflammation in mouse ear.
AB  - Topical cyclosporin A (CsA) was compared with dexamethasone, indomethacin and
      phenidone in edema, increases in vascular permeability, eicosanoids and cell
      influx induced by arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) in
      mouse ears. CsA ED(50) on AA-edema (7.7 micrograms/ear) was similar to
      dexamethasone and lower than indomethacin and phenidone. CsA ED(50) in TPA edema
      (21 micrograms/ear) was higher than dexamethasone and lower than indomethacin or
      phenidone. All drugs equally reduce the AA-induced increase in vascular
      permeability, but CsA and dexamethasone had more activity on TPA. AA-increase in
      vascular 6-keto-PGF1 alpha was reduced by dexamethasone, indomethacin and
      phenidone but not by CsA; only phenidone reduced LTB4. TPA-increase in 6-keto
      PGF1 alpha was reduced by CsA and indomethacin while CsA, dexamethasone and
      phenidone decreased LTB4. CsA, indomethacin and phenidone, but not dexamethasone,
      suppressed AA-neutrophil influx. In TPA-ears all drugs produced similar reduction
      in neutrophil influx. CsA was shown to be a good topical anti-inflammatory drug.

PMID- 9246580
TI  - Advances in acute pain management.

PMID- 9246582
TI  - Neuropathic pain in the perioperative period.
AB  - The presence of neuropathic pain in the postoperative period may be associated
      with unnecessary suffering, particularly if the diagnosis is not made and
      treatment modalities chosen are ineffective. It is likely that inadequate
      management of acute pain may set the scene for progression to a chronic pain
      state. The underlying neurobiological mechanisms whereby short-term stimuli may
      lead to long-term plasticity and structural changes in the nociceptive pathways
      are now being unraveled. The possibility arises that acute, intensive
      intervention may avoid or significantly reduce the development of these changes
      and subsequent chronic pain. Early diagnosis and treatment becomes a priority.
      There is a need for further research in this area to determine whether or not
      such theoretical potential can be turned to therapeutic advantage.

PMID- 9246581
TI  - New opioid analgesics: an update.

PMID- 9246583
TI  - Acute pain and the obstetric patient: recent developments in analgesia for labor
      and delivery.

PMID- 9246584
TI  - Acute pain management in pediatric patients.

PMID- 9246585
TI  - Neural blockade in chronic and cancer pain.
AB  - Neural blockade can provide significant pain relief to patients with chronic and
      cancer pain but must be used in the correct manner and only on selected patients.
      The hazards of performing neurolytic treatments have become apparent with time
      and demonstrate the need to examine the long-term outcomes of these procedures.
      The present challenge is to identify with controlled trials those patients with
      chronic pain who would benefit from neural blockade.

PMID- 9246586
TI  - Cognitive-behavioral programs: theory and application.

PMID- 9246587
TI  - Neuraxial implants for pain control.

PMID- 9246588
TI  - Education in pain management.

PMID- 9246589
TI  - The changing risk assessments for crystalline silica.

PMID- 9246590
TI  - Laboratory studies on silica induced toxicity and relationship to
      carcinogenicity.
AB  - A review of published laboratory studies was undertaken to provide insight into
      the biologic basis for silica induced lung toxicity. Experimental animals exhibit
      markers of silica induced toxicity similar to those exhibited by humans and may
      also provide a model for resistant populations. Cell culture studies are useful
      to discern the roles of specific lung cell types and cell mediators in the
      development of silica induced fibrotic events. The biochemical relationships
      between silica induced fibrosis and carcinogenesis have not been fully
      established. Temporal and dose-response relationships for events linking the two
      endpoints are unknown. Research in this area will provide a more complete
      understanding of the relationship between the two disease states and hence of the
      role of silica exposure in human disease.

PMID- 9246591
TI  - Industrial hygiene sampling and applications to ambient silica monitoring.
AB  - Interest in ambient exposures to silica has prompted an evaluation of the
      applicability of the industrial hygiene sampling and analysis experience.
      Exposure to excessive levels of silica in the workplace has long been recognized
      as a risk factor for the development of a variety of disabling and sometimes
      fatal lung diseases. Initial efforts to control occupational exposure to dust
      were based on reducing exposures as measured by particle-counting techniques.
      Because silicosis, the disease resulting from exposure to silica, occurs in the
      lower airways, which can be reached only by small "respirable dust" particles,
      size selective sampling procedures were introduced for dust monitoring. The
      analysis of silica in collected dust samples also has undergone development.
      Initial methods used involved acid digestion of soluble silicates, with
      subsequent chemical analysis of the insoluble "free silica" fraction. Current
      methodology relies on the use of X-ray diffraction and infrared technologies to
      quantify these materials. However, these methods are sensitive to the particle
      size distribution of the samples. Standard reference materials (SRMs) have been
      developed for use with respirable size dust samples. Ambient particulate matter
      is now measured using the U.S. Environmental Protection Agency sampling methods
      for particulate matter < or = 10 microns, which approximate the collection
      efficiency for thoracic fraction samplers. Because the existing calibration SRMs
      were produced for the measurement of occupational crystalline silica, the need to
      develop appropriate standards and methods for ambient silica measurements should
      be evaluated.

PMID- 9246592
TI  - Evidence for silica's neoplastic risk among workers and derivation of cancer risk
      assessment.
AB  - Although there has been debate in the medical community about silica's
      carcinogenicity since the 1930s, only in the past decade have there emerged
      scientific data supporting a causal association between industrial silica
      exposure and lung cancer. This paper examines the evidence for the association,
      with a particular focus on those studies appropriate for cancer risk assessment.
      The cancer risk extrapolations from epidemiology studies suggest that the levels
      of risks are approximately two factors less than that derived from animal
      studies. Additional research is needed to provide a stronger basis for the
      extrapolations so that policy makers can have more confidence in their estimates.

PMID- 9246593
TI  - Soil derived dust as a source of silica: aerosol properties, emissions,
      deposition, and transport.
AB  - Quartz is an abundant mineral in wind generated dust throughout the United
      States. Of the 18.9 million tons of particles smaller than 10 microns (PM10) dust
      emitted into the atmosphere by the wind, a significant fraction is silica.
      Transport of some of this silica to populated areas is possible.

PMID- 9246594
TI  - Initiating the risk assessment process for inhaled particulate materials:
      development of short term inhalation bioassays.
AB  - This study describes a short term inhalation bioassay in rats to predict the
      potential for inhaled particles to produce chronic lung disease in humans (e.g.,
      pulmonary fibrosis). To validate the method, rats were exposed for 6 h or 3 days
      to various concentrations of two reference materials: (1) a known fibrogenic
      material (i.e., aerosolized alpha-quartz silica particles in the form of Berkeley
      Min-U-Sil (Pennsylvania Glass and Sand Company, Pittsburgh, PA), or (2) carbonyl
      iron (CI) particles, as a negative control. Cells and fluids from groups of sham
      and dust exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline
      phosphatase, lactate dehydrogenase and protein values were measured in BAL fluids
      at several times postexposure. Cells were identified, counted, and evaluated for
      viability. The lungs of additional exposed animals were processed for
      histopathology. Although particle deposition patterns for the two dusts were
      similar, brief exposures to silica particles produced a persistent pulmonary
      inflammatory response characterized by neutrophil recruitment at sites of
      particle deposition and consistently elevated biomarkers of cytotoxicity in BAL
      fluids. In addition, alveolar macrophage clearance functions were impaired.
      Progressive histopathologic lesions were observed within 1 mo after a 3-day
      exposure. Light and electron microscopy of silica exposed lung tissue revealed a
      chronically active pulmonary inflammatory response characterized by hyperplasia
      of Type II alveolar epithelial cells and the infiltration of macrophages and
      neutrophils into alveoli and interstitial compartments. The lesions were
      progressive, leading to the development of a multifocal, granulomatous-type
      pneumonitis within 2 mo postexposure. In contrast to the observed effects of
      silica, 3-day exposures to CI particles produced no significant adverse
      biochemical or histopathological effects on pulmonary tissues. These results
      demonstrate that short term, high dose inhalation exposures of silica produce
      effects similar to those previously observed using intratracheal instillation or
      chronic inhalation models and lend support to this method as a reliable short
      term bioassay for evaluating the pulmonary toxicity and mechanisms associated
      with exposure to new and untested respirable materials.

PMID- 9246595
TI  - Ambient PM10 emissions: contributions and impact on silica emissions.
AB  - This paper reviews the ambient air literature and discusses the link between
      particulate matter with an MMAD < or = 10 micrograms (PM10) emissions and
      estimates of silica particulate concentrations. Silica appears to represent a
      range of 0.4-21% of PM10 emissions, although this estimation needs more research
      (including direct measurements) to contribute to increased confidence in the
      methodology.

PMID- 9246596
TI  - Noncancer inhalation toxicology of crystalline silica: exposure-response
      assessment.
AB  - Silicosis from inhalation of silica has long been recognized as an occupational
      hazard. Concern has arisen regarding the potential risk of silicosis from ambient
      silica (primarily quartz dust). This presentation reviews available data
      regarding ambient silica levels and estimates of the risk of silicosis at low
      exposure levels as they relate to the current U.S. Environmental Protection
      Agency National Ambient Air Quality Standards (NAAQS) for particulate matter.
      Current data indicate that for individuals not compromised by other respiratory
      ailments and for ambient environments expected to sustain 10% or less silica
      fraction in particulate matter with a mean aerodynamic diameter of < or = 10
      microns (PM10), maintenance of the 50 micrograms/m3 annual NAAQS for PM10 is
      adequate to protect against fibrotic effects from ambient silica exposures.
      Issues such as the large divergence of risk estimates within the occupational
      setting (particularly at high cumulative exposures) and factors to consider for
      extrapolating risk in an occupational setting to risk from ambient exposure are
      discussed.

PMID- 9246597
TI  - Cancer risk assessment for crystalline silica.

PMID- 9246598
TI  - Criteria for conducting quantitative risk assessments for silica.
AB  - Should quantitative risk assessment using epidemiologic data be performed for a
      substance such as silica dust? The criteria for conducting this step have been
      described by Hertz-Picciotto (1995) for individual epidemiology studies, and this
      paper applies the criteria to a body of cancer epidemiology research, indicating
      what the evidence is lacking. Discussion focuses on the cancer risk assessment
      calculations currently in the literature, the need for more research, and the
      relevance to decision making.

PMID- 9246599
TI  - The regulation of crystalline silica: an industry perspective.
AB  - Silica is ubiquitous in the earth's crust. It occurs in trace to large quantities
      in rocks and soil. Because it is so common, the regulation of silica has affected
      a large number of industries, including the mining industry and any industry that
      uses quartz in the manufacture of a products. Mineral commodities that contain
      silica include diatomite, bentonite, kaolinite, talc, pyrophyllite, sand and
      gravel, perlite, pumice, dimension stone, and barite. Products that contain
      minerals, many of which are associated with silica, include paint, paper, rubber,
      plastic, pharmaceuticals, food, cement, plaster, cat litter, potting soil,
      plaster board, and miscellaneous construction materials. In collaboration with
      some agencies and academic centers, the silica industry is supporting research to
      lower health risks and to improve the methods of detecting this common material.

PMID- 9246600
TI  - The link between silica dust levels, risk assessments, and regulations.
AB  - Improvements in workplace health among silica exposed workers followed
      demonstrations of the severity of the risk of silicosis and means of controlling
      high dust levels on the job. Current ambient environmental analyses include
      either an adoption of air quality goals for reducing emissions of criteria
      pollutants or the conduct of risk assessments to determine if regulatory
      procedures are needed. Although silica has been regulated as a workplace hazard
      for most of the 20th century, only recently has it been considered for ambient
      control, and most of the thrust for this action has evolved from environmental
      regulatory work in California, where both state initiative (Proposition 65) and
      legislative law (Air Toxics Hot Spots Information and Assessment Act; Assembly
      Bill number 2588) have required risk assessments for silica dust emissions as
      carcinogens.

PMID- 9246601
TI  - Effects of lipidic mediators on the growth of human myeloid and erythroid marrow
      progenitors.
AB  - Freshly isolated human marrow mononuclear cells produce lipidic compounds such as
      PAF and leukotrienes. These lipidic molecules act on human marrow myelopoiesis
      and erythropoiesis by modulating the growth of committed progenitors (CFU-GM and
      BFU-E) in vitro. Nanomolar concentrations of leukotriene B4 and C4 stimulate the
      growth of human marrow CFU-GM. In contrast, micromolar concentrations of
      lipoxygenase inhibitors (NDGA and BW755C) decrease their growth suggesting a role
      for endogenous lipoxygenase metabolites in this process. Micromolar
      concentrations of prostaglandin E2 up-regulate and down-regulate the growth of
      marrow BFU-E and CFU-GM, respectively. In contrast, the other cyclooxygenase
      metabolites have no effect. Recent studies indicate that nanomolar concentrations
      of PAF decrease the growth of CFU-GM and BFU-E from purified marrow CD34+ cells.
      Together these results indicate that lipidic mediators act on human myelopoiesis
      and erythropoiesis. However at this time the mechanisms and molecular signals
      mediating the effects of lipidic molecules on human marrow cells are unexplored.

PMID- 9246602
TI  - Evaluation of a trans configuration for the apoptosis-inducing activity of
      ceramide.
AB  - The requirement of a trans double bond for the biological action of ceramide was
      assessed by comparing the apoptosis-inducing activity of various ceramide
      analogs. The cis isomer and an acetylene type derivative of sphingosine were
      chemically synthesized, and the 2-amino moiety was acylated with hexanoic acid.
      These cell-permeable ceramide derivatives were compared with N-hexanoyl
      sphingosine (C6-Cer) or N-hexanoyl dihydrosphingosine (C6-DH-Cer) in their
      activity to induce apoptosis of HL60. Either the cis isomer of C6-Cer (C6-cis
      Cer) or a triple bond derivative (C6-TRP-Cer) induced apoptosis when assessed by
      fluorescence microscopy of the morphological changes and electrophoretic analysis
      of DNA C6-TRP-Cer yielded the highest percentage of apoptotic cells corresponding
      to three times that was induced by C6-Cer. C6-cis-Cer also showed stronger
      activity than C6-Cer. The minimum amounts of C6-TRP-Cer and C6-cis derivative
      required to induce apoptosis were 0.1 and 0.5 microM, respectively, while 1
      microM C6-Cer was required to exhibit the activity. C6-DH-Cer showed very low but
      significant activity above 10 microM. N-acetyl-sphingosine (C2-Cer) induced more
      apoptotic cells than C6-Cer, and C2-TRP-Cer was much more potent than C2-Cer.
      These observations suggest that the trans configuration of ceramide is not
      necessarily essential for the activity to induce apoptosis. In addition,
      distinctive activity of C6- or C2-TRP-Cer suggests that this ceramide analog
      might be useful for developing a new type of antitumor drug.

PMID- 9246603
TI  - Identification of sn-2 acetyl glycerophosphocholines in human keratinocytes.
AB  - Evidence is accumulating suggesting that platelet-activating factor plays a role
      in inflammatory dermatoses. Mass spectrometric methods were used to examine the
      molecular species of sn-2 acetyl glycerophosphocholines (GPC) synthesized by
      primary cultures of human neonatal foreskin-derived keratinocytes. Ionophore
      stimulated keratinocytes synthesize both 1-alkyl and 1-acyl sn-2 acetyl-GPC, and
      the relative amounts were as follows: hexadecyl > palmitoyl > octadecyl >
      stearoyl at the sn-1 position. PAF synthesis in the keratinocyte-derived cell
      line HaCaT was inhibited by dexamethasone, suggesting that the anti-inflammatory
      effects of glucocorticosteroids in inflammatory dermatoses might be in part
      related to the inhibition of the synthesis of mediators such as PAF.

PMID- 9246604
TI  - Platelet-activating factor and antagonists modulate DNA synthesis in human bone
      marrow stromal cell cultures.
AB  - Platelet-activating factor (PAF) is present in the human bone marrow. We have
      investigated the effect of PAF and antagonists (BN 52,021 and CV 3988) on the
      growth of human marrow stromal cells. PAF (1 microM) stimulates and PAF
      antagonists (0.1-1 microM) inhibit [3H]thymidine incorporation in cells grown in
      5% serum. The catabolism of PAF by stromal cells was inhibited by CV 3988
      suggesting the presence of specific PAF receptor on cells. PAF and antagonists
      (0.1 nM-10 microM) had no effect on cells cultured in high serum concentration
      (20%) or in low serum concentration (1%) with 0.5 ng/ml of basic fibroblast
      growth factor (bFGF). This study indicates for the first time that PAF modulates
      the serum-induced but not the bFGF-induced growth of marrow stromal cells. The
      interactions between PAF and stromal cells during inflammatory marrow events such
      as myelofibrosis deserve to be assessed.

PMID- 9246605
TI  - Post-receptor signal transduction and regulation of 14(R),15(S)
      epoxyeicosatrienoic acid (14,15-EET) binding in U-937 cells.
AB  - 14(R),15(S)-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P-450
      monooxygenase (epoxygenase) metabolite of arachidonic acid has been reported to
      induce adhesion of a monocyte cell line (U-937) to cultured endothelial cells. In
      this study, we identified a population of specific, high affinity binding sites
      for 14(R),15(S)-EET in U-937 cell surface with Kd of 13.84 +/- 2.58 nM and Bmax
      of 3.54 +/- 0.28 pmol/10(6) cells. The specific binding of [3H]-14,15-EET on U
      937 cells is more effectively displaced by 14(R),15(S)-EET than the 14(S),15(R)
      isomer thus indicating stereospecificity. The binding was sensitive to various
      protease treatments suggesting the binding site is protein in nature. 14,15-EET
      binding in U937 cells is attenuated by cholera toxin (CT) and dibutyryl cAMP.
      Mean binding site density (Bmax) decreased 31.61% and 34.8% by the pretreatment
      with cholera toxin (200 micrograms/ml) and dibutyryl cAMP (300 nM), respectively,
      without affecting the dissociation constant. Under similar conditions, pertussis
      toxin (20-200 ng/ml) was less effective as compared to CT and dibutyryl cAMP. The
      down regulation of 14,15-EET binding caused by dibutyryl cAMP in U-937 cell was
      reversed by a specific protein kinase A (PKA) inhibitor, H-89, but not by the PKC
      inhibitor K252a. Thus, the results suggest that the specific binding site of
      14,15-EET in U-937 cells is associated with a receptor that could be down
      regulated through an increase in intracellular cAMP and activation of a PKA
      signal transduction mechanism. We propose that the signal transduction mechanism
      of 14,15-EET begins with the binding of the receptor, which leads to the increase
      of intracellular cAMP levels and the activation of PKA, and finally with the down
      regulation of 14,15-EET receptor binding.

PMID- 9246606
TI  - A new phospholipase A2 inhibitor, unrelated to substrate analogues: kinetic
      characterization of the inhibition of secretory phospholipases A2 by PMS 832.
AB  - Starting from a series of compounds which were known to be PAF antagonists, we
      have synthesized molecules that are good inhibitors of PLA2s of groups I or II,
      with IC50 in the micromolar range (Binisti et al., 1997). In this report we
      investigate the mechanism of inhibition of bovine and porcine pancreatic
      phospholipases A2 (group I), and platelet lysate phospholipase A2 (group II) by
      one of these compounds, 1-(4'-methoxybenzoyl)-2-n-tridecylpiperazine (PMS 832).
      We show that PMS 832 behaves as a reversible, competitive inhibitor, with Ki
      values of 4.1 +/- 1.2 and 1.5 +/- 0.4 microM for porcine pancreatic phospholipase
      A2 and platelet lysate phospholipase A2, respectively. PMS 832 failed to inhibit
      platelet activation induced by several agonists and was also found to be inactive
      towards phospholipase C from Bacillus cereus, indicating a high specificity for
      phospholipase A2 inactivation. Thus, PMS 832 and its derivatives could serve as
      interesting tools to investigate the role of extracellular phospholipases A2 in
      inflammatory processes, and may be useful in the development of new anti
      inflammatory agents.

PMID- 9246607
TI  - Supplementation of MCF-7 cells with essential fatty acids induces the activation
      of protein kinase C in response to IGF-1.
AB  - The effects of changing the composition of membrane lipids on protein kinase C
      (PKC) activation were studied in MCF-7 human breast cancer cells. The supply of
      linoleate or alpha-linolenate to MCF-7 cells altered cell membranes fatty acid
      composition but did not affect PKC activity. When the cells were additionally
      exposed to IGF-1, the same fatty acids caused a dramatic increase in membrane
      bound PKC activity. We also found that the mitogenic response induced by IGF-1
      was not enhanced in those conditions when PKC becomes activated by linoleate and
      alpha-linolenate. These data show that these fatty acids elicit a distinct route
      for the transmission of IGF-1 signal by inducing the PKC pathway. They suggest
      that linoleate and alpha-linolenate could control the biological response of MCF
      7 cells to IGF-1.

PMID- 9246608
TI  - Roles of phospholipases A2 in brain cell and tissue injury associated with
      ischemia and excitotoxicity.
AB  - Phospholipase A2 (PLA2) activity is an important contributor to destructive
      cellular processes in the central nervous system. Two cytosolic forms of calcium
      dependent PLA2 have been characterized in the gerbil brain and the neuronal
      cultures from rat brain. PLA2 enzymatic activity in cell free extracts from
      cortical neuronal cultures is upregulated after cells are exposed to glutamate.
      Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA)
      stably enhanced PLA2 activity. Stable activation of the two cytosolic forms of
      PLA2 occur prior to evidence of cell death and this activation is reversible. The
      larger molecular mass form was characterized as cPLA2. The smaller form
      (approximately 14 kDa) was distinct from Group I and II PLA2. Exposure to
      glutamate shifted the calcium activation curve of the smaller form to the left
      suggesting a novel mechanism of regulation of PLA2. Glutamate-induced stable
      enhancement of PLA2 activity, by processes involving calcium and protein kinase C
      activation, is a potential molecular switch likely mediating changes in synaptic
      function and contributing to excitotoxicity.

PMID- 9246609
TI  - The Edman Award 1996.

PMID- 9246610
TI  - High-sensitivity detection of 4-(3-pyridinylmethylaminocarboxypropyl)
      phenylthiohydantoins by capillary liquid chromatography-microelectrospray ion
      trap mass spectrometry.
AB  - We describe the separation and detection at the low-femtomole level of 4-(3
      pyridinylmethylaminocarboxypropyl) phenylthiohydantoins (311-PTHs) by capillary
      liquid chromatography-microelectrospray ion trap mass spectrometry. Highest
      sensitivity was obtained in the multiple-ion monitoring operating mode in which
      we detected 311-PTHs at the 5-fmol level with a signal-to-noise ratio of
      approximately 10. We investigated the fragmentation patterns of the isobaric 311
      PTH isoleucine and 311-PTH leucine by electrospray ionization ion trap tandem
      mass spectrometry. The compounds could be differentiated by a fragment ion of
      mass m/z = 366.1 which was specific for the breakdown of 311-PTH leucine, thus
      allowing for the unambiguous identification of the 311-PTH derivatives of all 20
      naturally occurring amino acids by their masses and fragmentation patterns.

PMID- 9246611
TI  - Determination of phosphorylation sites in peptides and proteins employing a
      volatile Edman reagent.
AB  - A manual Edman degradation protocol has been developed that allows the
      identification of phosphorylation sites in 32P-labeled peptides at the
      subpicomole level. By using both a volatile reagent, trifluoroethyl
      isothiocyanate, and volatile buffers, extraction steps are rendered unnecessary
      and cycle times can be reduced to 45 min. The protocol was employed to identify
      the site of phosphorylation in phosphoserine- and phosphotyrosine-containing
      peptides.

PMID- 9246612
TI  - Novel techniques for identification and characterization of proteins loaded on
      gels in femtomole amounts.
AB  - A combination of techniques is presented allowing gel-purified protein
      identification in the femtomole range using matrix-assisted-laser-desorption
      ionization mass spectrometry. The proteins are detected in the primary gel by a
      sensitive negative staining procedure, transferred, and concentrated in a
      secondary gel matrix. There, they are digested in the presence of H218O and their
      sequences are predicted (1) by peptide mass fingerprinting, (2) by comparing the
      post-source-decay (PSD) spectra with theoretical spectra of candidate isobaric
      peptides using a computer algorithm called MassFrag, and (3) by a manual readout
      of the 18O/16O-labeled fragmentation ions in the PSD spectra.

PMID- 9246613
TI  - Automated protein preparation techniques using a digest robot.
AB  - Since the introduction of fast analysis methods for peptide mixtures such as
      MALDI-MS, peptide micropreparation and digest methods have become an important
      bottleneck in the protein characterization process. We therefore developed and
      describe here a digest robot capable of processing 30 protein samples in parallel
      [Houthaeve et al. (1995), FEBS Lett. 376, 91-94]. Briefly, after gel pieces or
      blots are cut out, they are loaded in flowthrough reactors and these are loaded
      in a thermocontrolled reactor block. The proteins are then washed, reduced, and
      alkylated, proteolytically or chemically cleaved, and resulting peptides
      extracted. The system allows the parallel use of different reagents and enzymes
      during the same run, and is compatible with RP-HPLC peptide separation and Edman
      degradation, MALDI-MS, and NanoES-MS/MS. The digest robot is now also
      commercially available from ABIMED. In an ongoing project aimed at elucidating
      proteinaceous structures involved in the functional and structural maintenance of
      the Golgi apparatus, we illustrate the strength of the digest robot for the fast
      analysis of several proteins. We conclude that the performance of the digest
      robot is comparable to currently used manual digestion methods. The approach
      outlined makes sample preparation procedures faster, simpler, and less labor
      intensive.

PMID- 9246614
TI  - High-sensitivity peptide mapping by micro-LC with on-line membrane blotting and
      subsequent detection by scanning-IR-MALDI mass spectrometry.
AB  - A novel approach to the on-line mass determination of peptides from digested
      proteins by scanning infrared matrix-assisted laser desorption/ionization
      (scanning-IR-MALDI) is described. The peptides were continuously collected
      directly onto a PVDF (polyvinylidene fluoride) strip during a HPLC run.
      Individual peptides were detected by lining up the PVDF strip with the UV trace
      from the HPLC run, using visible dye markers as reference points. The local
      resolution of the peptides on the PVDF membrane is preserved during matrix
      incubation for MALDI-MS as shown by comparing the UV chromatogram and the total
      ion current (TIC) from an on-line coupled electrospray ionization (ESI) mass
      spectrometer with the scanning-IR-MALDI data from the corresponding areas on the
      PVDF strip. The intensities of the mass profiles obtained by scanning-IR-MALDI
      reflect the amount of peptides present on the PVDF strip. The higher sensitivity
      of IR-MALDI-MS yielded mass information not detectable by ESI-MS. After the
      scanning-IR-MALDI experiment, the same membrane strip can be used directly for
      automated Edman degradation. Comparable initial and repetitive yields were
      obtained for blotted peptides with and without matrix incubation.

PMID- 9246615
TI  - Accurate mass measurements using MALDI-TOF with delayed extraction.
AB  - Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry is now an essential tool in biopolymer analysis. Sensitivity and
      mass range are unsurpassed, but mass measurement accuracy and resolution have
      been limited. With delayed extraction and a reflecting analyzer, mass
      measurements using MALDI-TOF can be made with an accuracy of a few parts per
      million (ppm). It is possible to distinguish Lys from Gln in peptides, and to
      determine the elemental composition of smaller molecules (mass 100-500). In
      database searching strategies, a smaller mass window, resulting from an increase
      in mass accuracy, greatly decreases the number of possible candidates. Mass
      measurement accuracy with errors less than 5 ppm is demonstrated on a mixture of
      12 peptides ranging in mass from ca. 900 to 3700 Da. Mass measurements on 13
      peaks in an unseparated tryptic digest of myoglobin gave results with an overall
      average error less than 3.5 ppm, with a maximum error of 7 ppm.

PMID- 9246616
TI  - C-terminal sequence determination of modified peptides by MALDI MS.
AB  - Peptides, cleaved by a mixture of carboxypeptidases CPP and CPY, can be detected
      by MALDI MS and the amino acid sequence thereby determined by calculation of the
      differences between consecutive peaks. In the present study we have used
      derivatizations of Lys and Cys to facilitate identification of these residues.
      Since the mass values do not readily distinguish Lys from Gln, we have converted
      Lys to homoarginine by guanidination, allowing simple detection of Lys. To
      identify the Cys positions in peptides that contain cystine, cysteic acid, or
      carboxymethylcysteine is not possible using CPY and CPP because of the lack of
      proteolytic cleavage. Instead we find that identification of Cys residues within
      the sequence can be achieved after conversion to a basic derivative, 4
      thialaminine (Thi), by trimethylaminoethylation.

PMID- 9246617
TI  - Contact sites of peptide-oligoribonucleotide cross-links identified by a
      combination of peptide and nucleotide sequencing with MALDI MS.
AB  - We have investigated peptide-oligoribonucleotide complexes isolated from cross
      linked Escherichia coli 30S ribosomal subunits in order to identify the contact
      sites of these complexes at the molecular level. For this purpose, reversed-phase
      (RP) HPLC-purified peptide-oligoribonucleotide complexes were submitted to N
      terminal amino acid sequencing in order to determine the cross-linked peptide
      moiety and were analyzed using matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) for calculation of the nucleotide composition of the
      cross-linked complex. Subsequently, for nucleotide sequence information the
      complexes were partially hydrolyzed or treated with exonucleases and analyzed
      again by MALDI-MS. Applying this technique, we were able to identify the cross
      linked oligoribonucleotide parts in contact with distinct peptide regions derived
      from ribosomal proteins S4, S7, S8, and S17 from E. coli.

PMID- 9246618
TI  - Mammalian sperm tubulin: an exceptionally large number of variants based on
      several posttranslational modifications.
AB  - Extraction of demembranated bull sperm flagella by SDS was used to maximize
      tubulin solubilization. The alpha- and beta-tubulin separated by SDS-PAGE were
      treated with endoproteinases LysC and AspN, respectively. Carboxy-terminal
      fragments were isolated by Mono Q chromatography and reversed-phase HPLC.
      Automated sequencing and mass spectrometry revealed an astonishingly high number
      of tubulin variants. Many variants were due to polyglutamylation and in
      particular to polyglycylation. The number of side-chain glycyl residues ranged
      from 0 to 28 in alpha and 0 to 15 in beta. Corresponding values for side-chain
      glutamyl residues were 0-6 in alpha and 0-3 in beta. Additional alpha variability
      was based on carboxy-terminal detyrosination and partial loss of the penultimate
      glutamate. A major glycylation site in alpha- and beta-tubulin was mapped. Some
      variants seem to display both glycyl and glutamyl side chains.

PMID- 9246619
TI  - The essential role of mass spectrometry in characterizing protein structure:
      mapping posttranslational modifications.
AB  - Over the last few years we have developed mass spectrometry-based approaches for
      selective identification of a variety of posttranslational modifications, and for
      sequencing the modified peptides. These methods do not involve radiolabeling or
      derivatization. Instead, modification-specific fragment ions are produced by
      collision-induced dissociation (CID) during analysis of peptides by ESMS. The
      formation and detection of these marker ions on-the-fly during the LC-ESMS
      analysis of a protein digest is a powerful technique for identifying
      posttranslationally modified peptides. Using the marker ion strategy in an
      orthogonal fashion, a precursor ion scan can detect peptides which give rise to a
      diagnostic fragment ion, even in an unfractionated protein digest. Once the
      modified peptide has been located, the appropriate precursor ion can be sequenced
      by tandem MS. The utility and interplay of this approach to mapping PTM is
      illustrated with examples that involve protein glycosylation and phosphorylation.

PMID- 9246620
TI  - Posttranslational modifications of axonemal tubulin.
AB  - Axonemal tubulin exhibits a high degree of heterogeneity mostly due to several
      posttranslational modifications (PTM). The aim of this work was to chemically
      characterize the different PTM occurring in the C-terminal tail of axonemal
      tubulin purified from sea urchin, Paracentrotus lividus, spermatozoa. After its
      purification, tubulin was enzymatically cleaved. The C-terminal peptides were
      chromatographically isolated, first by anion exchange and then by reverse-phase
      HPLC. Peptides were characterized by their sequence, determined by Edman
      degradation, and by their mass, determined by MALDI-TOF/MS. The two major
      conclusions are that the majority of the isolated C-terminal peptides were
      unmodified and that polyglycylation and polyglutamylation can occur
      simultaneously on one molecule of alpha-tubulin.

PMID- 9246621
TI  - High-sensitivity mass spectrometry for analysis of posttranslational
      modifications.
AB  - Pulsed fast atom bombardment ionization (pulsed-FAB) mass spectrometry has been
      developed to improve the sensitivity of tandem mass spectrometry (MS/MS),
      allowing it to be used for the analysis of very small samples. MS/MS, when used
      with a magnetic four-sector instrument coupled with the pulsed-FAB system, allows
      significant enhancement in product ion intensity of over ten-fold in magnitude
      over conventional FAB. MS/MS was applied to the structural analysis of a unique
      nuclear protein, designated p28, which was isolated from a histone fraction
      obtained from starfish testes. The results clearly show that protein p28 is a
      heterodimer composed of testicular histones H2B and H4 which are cross-linked
      between Gln9 of H2B and Lys5 of H4.

PMID- 9246623
TI  - Combination of micropreparative capillary electrophoresis and matrix-assisted
      laser desorption/ionization mass spectrometry for peptide analysis.
AB  - Signal suppression is a problem in matrix-assisted laser desorption/ionization
      mass spectrometry of peptides prepared by capillary electrophoresis. Many common
      electrolytes that are efficient for separation, such as sodium phosphate, also
      are strongly suppressive during laser desorption/ionization. We have tested
      individual electrolytes for highest performance in each step of separation and
      collection, respectively. Suppression is not observed if citrate, trifluoroacetic
      acid, or hydrochloric acid is used for collection, while phosphate still can be
      employed in the capillary providing excellent resolution. Low concentrations of
      hydrochloric acid added to the sample/matrix mixture generate mass spectra with
      better ion intensities than if trifluoroacetic acid or citrate is used.

PMID- 9246622
TI  - High yield elution of proteins from sodium dodecyl sulfate-polyacrylamide gels at
      the low-picomole level. Application to N-terminal sequencing of a scarce protein
      and to in-solution biological activity analysis of on-gel renatured proteins.
AB  - A simple, reliable procedure for practically quantitative (90-98%) and fast (< 30
      min) elution of proteins from SDS-PA gels is described with reproducible
      recoveries in the range from 100 to 1 pmol per band, which does not require the
      inclusion of detergents in the elution buffer. It consists in the combination of
      (1) highly sensitive on-gel protein detection (50 mol per band) with imidazole
      SDS-zinc (reverse staining), (2) crushing of the protein band to produce 32
      micron gel particles, and (3) vortexing of the slurry in a solution of a zinc
      complexing agent, e.g. glycine 0.5 M or EDTA 100 mM (100 microliters for a 100
      pmol BSA band), at room temperature. Eluted proteins can be directly analyzed by
      RP-HPLC, quantitatively loaded onto a PVDF membrane, or, provided that they are
      previously renatured on-gel, analyzed by biological activity tests. The
      application of the procedure to in-solution enrichment of scarce proteins for N
      terminal analysis is shown.

PMID- 9246624
TI  - Fabrication of stable packed capillary reversed-phase columns for protein
      structural analysis.
AB  - Capillary column (< or = 320-micron ID) liquid chromatography is an essential
      tool for the separation and concentration of low-picomole amounts of proteins and
      peptides for mass-spectrometric based structural analysis. We describe a detailed
      procedure for the fabrication of stable and efficient 50- to 180-micron ID
      polyimide fused-silica columns. Columns were packed by conventional slurry
      packing with reversed-phase silica-based supports followed by column bed
      consolidation with acetonitrile and sonication. PVDF membrane or internal fused
      silica particles were employed for column end-frit construction. The ability of
      these columns to withstand high back pressures (300-400 bar) enabled their use
      for rapid chromatography (> 3400 cm/hr; i.e., approximately 40 microliters/min
      for 200-micron ID columns) and the loading of large sample volumes (up to 500
      microliters). The accurate low flow rates (0.4-4.0 microliters/min) and precise
      gradient formation necessary to operate these columns were achieved by a simple
      modification of conventional HPLC systems [Moritz et al. (1992), J. Chromatogr.
      599, 119-130]. Column performance was evaluated for ability to resolve low-fmol
      amounts of all components of a mixture of PTH-amino acids and to separate
      peptides for on-line LC/MS analysis of peptide mixtures derived from in situ
      digestion of 2-DE resolved protein spots.

PMID- 9246625
TI  - The "pre-molten globule," a new intermediate in protein folding.
AB  - In vitro folding studies of several proteins revealed the formation, within 2-4
      msec, of transient intermediates with a large far-UV ellipticity but no amide
      proton protection. To solve the contradiction between the secondary structure
      contents estimated by these two methods, we characterized the isolated C-terminal
      fragment F2 of the tryptophan synthase beta 2 subunit. In beta 2, F2 forms its
      tertiary interactions with the F1 N-terminal region. Hence, in the absence of F1,
      isolated F2 should remain at an early folding stage with no long-range
      interactions. We shall show that isolated F2 folds into, and remains in, a
      "state" called the pre-molten globule, that indeed corresponds to a 2- to 4-msec
      intermediate. This condensed, but not compact, "state" corresponds to an array of
      conformations in rapid equilibrium comprising native as well as nonnative
      secondary structures. It fits the "new view" on the folding process.

PMID- 9246626
TI  - Classification of the environment of protein residues.
AB  - We have studied the classification of the environment of residues within protein
      structures. Eisenberg's original idea created environmental categories to
      discriminate between similar residues [Bowie et al., Science (1991), 253, 164
      170]. These environments grouped residues based upon their buried surface area,
      polarity of the surrounding environment, and secondary structure element in which
      the residue is found. However, Eisenberg's original categories led to incomplete
      discrimination between residues that only partially substitute for each other. We
      have expanded on Eisenberg's original idea of environmental categories, by both
      considering additional contacts in the calculation of the solvent-accessible
      molecular surface area and by subdividing the environmental plot into regions
      based upon its theoretical features. Our alternative surface area calculations
      were used in conjunction with the polarity of the environment of the residue to
      define a new set of environmental categories. These new categories were able to
      discriminate between residues such as threonine, valine, and aspartic acid while
      reflecting the propensity of these residues to substitute for each other.

PMID- 9246627
TI  - Dead-end based modeling tools to explore the sequence space that is compatible
      with a given scaffold.
AB  - The dead-end elimination algorithm has proven to be a powerful tool in protein
      homology modeling since it allows one to determine rapidly the global minimum
      energy conformation (GMEC) of an arbitrarily large collection of side chains,
      given fixed backbone coordinates. After introducing briefly the necessary
      background, we focus on logic arguments that increase the efficacy of the dead
      end elimination process. Second, we present new theoretical considerations on the
      use of the dead-end elimination method as a tool to identify sequences that are
      compatible with a given scaffold structure. Third, we initiate a search for
      properties derived from the computed GMEC structure to predict whether a given
      sequence can be well packed in the core of a protein. Three properties will be
      considered: the nonbonded energy, the accessible surface area, and the extent by
      which the GMEC side-chain conformations deviate from a locally optimal
      conformation.

PMID- 9246628
TI  - Prediction of membrane protein topology utilizing multiple sequence alignments.
AB  - A technique for prediction of protein membrane topology (intra- and extracellular
      sidedness) has been developed. Membrane-spanning segments are first predicted
      using an algorithm based upon multiply aligned amino acid sequences. The
      compositional differences in the protein segments exposed at each side of the
      membrane are then investigated. The ratios are calculated for Asn, Asp, Gly, Phe,
      Pro, Trp, Tyr, and Val, mostly found on the extracellular side, and for Ala, Arg,
      Cys, and Lys, mostly occurring on the intracellular side. The consensus over
      these 12 residue distributions is used for sidedness prediction. The method was
      developed with a set of 42 protein families for which all but one were correctly
      predicted with the new algorithm. This represents an improvement over previous
      techniques. The new method, applied to a set of 12 membrane protein families
      different from the test set and with recently determined topologies, performed
      well, with 11 of 12 sidedness assignments agreeing with experimental results. The
      method has also been applied to several membrane protein families for which the
      topology has yet to be determined. An electronic prediction service is available
      at the E-mail address tmap@embl-heidelberg.de and on WWW via http://www.embl
      heidelberg.de.

PMID- 9246629
TI  - Analysis and organization of protein sequence data: a retrospective spanning four
      decades.
AB  - Protein sequence data are as useful and valuable today as was envisioned by
      pioneering sequencers and by the organizers of the first sequence database.
      Sequence analysis was first the province of specialists who developed search,
      comparison, and tree-building methods. Microcomputers, communication satellites,
      and the Internet have made these methods accessible to any scientist. The rapid
      increase in the data has driven a succession of changes in how databases are
      compiled, distributed, and accessed. Large public databases have become
      international collaborations. Although they need to develop still more efficient
      ways to accumulate, organize, annotate, and standardize huge amounts of data,
      inadequate support is available for such efforts. Thus there will be greater
      reliance on direct input from the scientific community. The World Wide Web is
      essential but not sufficient for integrated access to related databases.

PMID- 9246630
TI  - From gel filtration to adsorptive size exclusion.
AB  - Adsorption and size exclusion in starch and cross-linked dextran were phenomena
      discovered in Uppsala in the 1950s [Porath (1979), Biochem. Soc. Trans. 7, 1197;
      Porath (1981), Current Content 19, 21; Porath (1981), J. Chromatogr. 218, 241;
      Janson (1987), Chromatographia 23, 361; Laurent (1993), J. Chromatogr. 633, 1].
      These discoveries were the background to the development of a variety of affinity
      chromatographic methods. At present attempts are being made to combine size
      exclusion chromatography (SEC) with adsorption into a single operation that we
      call adsorptive SEC (AdSEC).

PMID- 9246631
TI  - A novel geometry mass spectrometer, the Q-TOF, for low-femtomole/attomole-range
      biopolymer sequencing.
AB  - Ultra-high-sensitivity, biopolymer sequencing is a goal in many fields of
      molecular biology, and collisionally activated decomposition electrospray mass
      spectrometry (CAD ES MS/MS) using a triple quadrupole mass spectrometer has
      become a method of choice for work in the high- to mid-femtomole range. However,
      when the detection of ions becomes statistical, as it may in that range, the mass
      assignment of fragment ions is inaccurate and either sequencing becomes
      impossible or ambiguities result due, for example, to the closeness in amino acid
      residue masses (I/L, N or K/Q, E). Some ambiguities may be resolved by
      synthesizing possible sequences, but this is unsatisfactory. In considering the
      limitations of triple quadrupole MS/MS with respect to scanning ion detection,
      resolution, transmission, and mass accuracy, we reasoned that a novel geometry
      quadrupole orthogonal acceleration time-of-flight (Q-TOF) instrument would have
      special merit for ultra-high-sensitivity MS/MS sequencing, and suggested its
      construction for this purpose some three years ago. A prototype Q-TOF has now
      been built by Micromass [Morris et al. (1996), Rapid Commun. Mass Spectrom. 10,
      889-896], and in the first research on the instrument, including MHC antigen and
      filarial nematode glycoprotein studies, we demonstrate low-femtomole- and
      attomole-range sequencing with mass accuracy of better than 0.1 Da throughout the
      daughter-ion spectrum, thus removing sequencing ambiguities in some of the most
      challenging work demanding the highest sensitivity.

PMID- 9246632
TI  - Peptide sequencing by mass spectrometry for homology searches and cloning of
      genes.
AB  - It is now possible to obtain sequence information from gel-separated proteins by
      mass spectrometry at levels too low for conventional approaches. Usually this
      tandem mass spectrometric data are used for database searches with the aim of
      identifying the corresponding gene. Recently it has been shown that long and
      accurate amino acid sequences can be obtained which are sufficient for PCR-based
      strategies to clone the corresponding gene [Wilm et al. (1996), Nature 379, 466
      469]. More than eight proteins have now been cloned based on that method. In many
      more cases the sequence information identified homologous proteins. Issues
      involved in cloning by mass spectrometric sequence information are discussed, as
      are two case studies. These results clearly establish mass spectrometry as a
      viable tool not only for the database identification of proteins, but also for
      the de novo sequencing of gel-separated proteins at the low-picomole to femtomole
      level.

PMID- 9246633
TI  - Double coupling Edman chemistry for high-sensitivity automated protein
      sequencing.
AB  - Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) is a
      promising new method for the analysis of protein sequencing products. It gives 10
      zmol (1 zmol = 10(-21) mol) limits of detection (3 sigma) for fluorescein
      thiohydantoin (FTH) amino acids. We have developed a separation for the (FTH)
      amino acid products generated from 18 of the 20 coded amino acids. The extremely
      low volume requirement associated with CE-LIF makes it incompatible with
      commercial sequencers. For this reason, we have also been developing a
      miniaturized sequencer that can be more easily coupled to our detection system.
      Both the CE-LIF system and the miniaturized sequencer are described.

PMID- 9246634
TI  - Direct analysis of protein mixtures by tandem mass spectrometry.
AB  - Methods to identify proteins contained in mixtures are described. The approach
      uses microcolumn liquid chromatography and automated tandem mass spectrometry in
      conjunction with protein and nucleotide database searching algorithms. This
      approach is applied to the identification of proteins obtained by
      immunoprecipitation reactions, interaction with a GST protein fusion products and
      interaction with a macromolecular complex.

PMID- 9246635
TI  - A phage display technique for a fast, sensitive, and systematic investigation of
      protein-protein interactions.
AB  - Phage display is a technique in which a foreign protein or peptide is presented
      at the surface of a (filamentous) bacteriophage. This system, developed by Smith
      [(1985), Science 228, 1315-1317], was originally used to create large libraries
      of antibodies for the purpose of selecting those that strongly bound a particular
      antigen. More recently it was also employed to present peptides, domains of
      proteins, or intact proteins at the surface of phages, again to identify high
      affinity interactions with ligands. Here we want to illustrate the use of phage
      display, in combination with PCR saturation mutagenesis, for the study of protein
      protein interactions. Rather than selecting for mutants having high affinity, we
      systematically investigate the binding of every variant with its natural ligand.
      Via a modified ELISA we can calculate a relative affinity. As a model system we
      chose to display thymosin beta 4 on the phage surface in order to study its
      interaction with actin.

PMID- 9246636
TI  - Affinity selection and mass spectrometry-based strategies to identify lead
      compounds in combinatorial libraries.
AB  - The screening of diverse libraries of small molecules created by combinatorial
      synthetic methods is a recent development which has the potential to accelerate
      the identification of lead compounds in drug discovery. We have developed a
      direct and rapid method to identify lead compounds in libraries involving
      affinity selection and mass spectrometry. In our strategy, the receptor or target
      molecule of interest is used to isolate the active components from the library
      physically, followed by direct structural identification of the active compounds
      bound to the target molecule by mass spectrometry. In a drug design strategy,
      structurally diverse libraries can be used for the initial identification of lead
      compounds. Once lead compounds have been identified, libraries containing
      compounds chemically similar to the lead compound can be generated and used to
      optimize the binding characteristics. These strategies have also been adopted for
      more detailed studies of protein-ligand interactions.

PMID- 9246637
TI  - Structure and sites of phosphorylation of 14-3-3 protein: role in coordinating
      signal transduction pathways.
AB  - The 14-3-3 family are homo- and heterodimeric proteins whose biological role has
      been unclear for some time, although they are now gaining acceptance as a novel
      type of 'adaptor' protein that modulates interactions between components of
      signal transduction pathways, rather than by direct activation or inhibition. It
      is becoming apparent that phosphorylation of the binding partner and possibly
      also the 14-3-3 proteins may regulate these interactions. 14-3-3 isoforms
      interact with a novel phosphoserine (Sp) motif on many proteins, RSX1,2SpXP. The
      two isoforms that interact with Raf-1 are phosphorylated in vivo on Ser185 in a
      consensus sequence motif for proline-directed kinases. The crystal structure of
      14-3-3 indicates that this phosphorylation could regulate interaction of 14-3-3
      with its target proteins. We have now identified a number of additional
      phosphorylation sites on distinct mammalian and yeast isoforms.

PMID- 9246638
TI  - A multidimensional approach to protein characterization.
AB  - When mass spectrometry (MS) is used to study protein primary structure, it is
      used in a "static" mode. That is, the information is derived from a single MS or
      MS-MS spectrum. Information about more complex protein structure or protein
      interactions can also be gained via MS. If a series of mass spectra is collected
      as something else in the experiment is changing, we increase the "dimensionality"
      of the MS data. For example, measuring mass spectra as a function of time after
      exposure of a protein to deuterated solvents can provide information about
      protein structure. Likewise, by measuring mass spectra of a protein as the
      concentration of a binding ligand is changed, one can infer the stoichiometry of
      the complex. Another important, but fundamentally different way of increasing the
      dimensionality of mass spectral data is by coupling the mass spectrometer to a
      one- or two-dimensional separation technique.

PMID- 9246640
TI  - Screening of rice genes from the cDNA catalog using the data obtained by protein
      sequencing.
AB  - The partial amino acid sequences of 121 rice proteins separated by two
      dimensional gel electrophoresis (2D-PAGE), were determined for a protein sequence
      data file. In the Rice Genome Research Program (RGP), more than 20,000 cDNA
      clones randomly selected from rice cDNA libraries have been sequenced to
      construct a cDNA catalog. Complimentary DNAs encoding about 30% of proteins in
      the protein sequence data file could be identified in the catalog by computer
      search. It was deduced that 20,000-40,000 genes are present in the rice genome.
      Only half of about 20,000 cDNAs sequenced in the RGP, corresponding to 1/4-1/2 of
      genes present in the entire rice genome, should have unique sequences after
      considering gene redundancy. This is consistent with the fact that the cDNAs
      encoding about 30% of the sequenced proteins could be identified in the catalog.
      If the size of the cDNA catalog is enlarged further, cDNAs encoding all proteins
      separated by 2D-PAGE could be easily identified from the catalog by using the
      protein sequence data.

PMID- 9246639
TI  - Probing the influence of mutations on the stability of a ferredoxin by mass
      spectrometry.
AB  - Hydrogen/deuterium exchange, which depends on solvent accessibility, can be
      probed by mass spectrometry (MS) to get information on protein conformation or
      protein-ligand interaction. In this work, the conformational properties of the
      cyanobacterium Anabaena wild-type ferredoxin as well as of two single-site
      mutants (Phe 65 Ala and Arg 42 Ala) were studied. After incubation of the wild
      type and mutant proteins in deuterated water and quenching of the exchange at low
      pH, the proteins were rapidly digested at high enzyme-to-substrate ratio using
      immobilized pepsin, and the resulting peptides were characterized using ESI-MS.
      We have identified specific regions for which the H-bonding or solvent
      accessibility properties were perturbed by the mutations. These results show that
      this approach can provide local information on the influence of mutations, even
      for a highly structured protein like ferredoxin, and sometimes in regions distant
      from the mutation point.

PMID- 9246641
TI  - Proteome analysis: genomics via the output rather than the input code.
AB  - A knowledge of the 'proteome,' total protein output encoded by a genome, provides
      information on (1) if and when predicted gene products are translated, (2) the
      relative concentrations of gene products, and (3) the extent of posttranslational
      modification, none of which can be accurately predicted from the nucleic acid
      sequence alone. The current status of proteome analysis is reviewed with respect
      to some of the techniques employed, automation, relevance to genomic studies,
      mass spectrometry and bioinformatics, limitations, and recent improvements in
      resolution and sensitivity for the detection of protein expression in whole
      cells, tissues, or organisms. The concept of 'proteomic contigs' is introduced
      for the first time. Traditional approaches to genomic analysis call upon a number
      of strategies to produce contiguous DNA sequence information, while 'proteomic
      contigs' are derived from multiple molecular mass and isoelectric point windows
      in order to construct a picture of the total protein expression within living
      cells. In higher eukaryotes, the latter may require several dozen image subsets
      of protein spots to be stitched together using advanced image analysis. The
      utility of both experimental and theoretical peptide-mass fingerprinting (PMF)
      and associated bioinformatics is outlined. A previously unknown motif within the
      peptide sequence of Elongation Factor Tu from Thermus aquaticus was discovered
      using PMF. This motif was shown to possess potential significance in maintaining
      structural integrity of the entire molecule.

PMID- 9246642
TI  - On the classification and evolution of protein modules.
AB  - Our efforts to classify the functional units of many proteins, the modules, are
      reviewed. The data from the sequencing projects for various model organisms are
      extremely helpful in deducing the evolution of proteins and modules. For example,
      a dramatic increase of modular proteins can be observed from yeast to C. elegans
      in accordance with new protein functions that had to be introduced in
      multicellular organisms. Our sequence characterization of modules relies on
      sensitive similarity search algorithms and the collection of multiple sequence
      alignments for each module. To trace the evolution of modules and to further
      automate the classification, we have developed a sequence and a module alerting
      system that checks newly arriving sequence data for the presence of already
      classified modules. Using these systems, we were able to identify an unexpected
      similarity between extracellular C1Q modules with bacterial proteins.

PMID- 9246643
TI  - Effect of phosphorylation on tetramerization of the tumor suppressor protein p53.
AB  - Human tumor suppressor protein p53 is a 393-amino acid phosphoprotein that
      enhances transcription in response to DNA damage from several genes that regulate
      cell cycle progression. The tetrameric state of p53 is critical to wild-type
      function; the p53 tetramerization element is located in the C-terminal region of
      the protein. This region is phosphorylated at several evolutionarily conserved
      serines, suggesting that phosphorylation may be an important regulator of p53
      function. In order to determine the effect of phosphorylation on tetramer
      formation, we synthesized phosphopeptides corresponding to p53(Ser303-Asp393)
      with phosphate incorporated at Ser315, Ser378, or Ser392, and at both Ser315 and
      Ser392. Equilibrium ultracentrifugation analysis showed that phosphorylation at
      Ser392 increased the association constant for tetramer formation nearly ten-fold.
      By itself, phosphorylation at Ser315 or Ser378 had little effect on tetramer
      formation, but Ser315 largely reversed the effect of phosphorylation at Ser392.
      Analysis by calorimetry suggests that phosphorylation may influence subunit
      affinity by an enthalpy driven process.

PMID- 9246645
TI  - Assessing the structure, content, and perceived social climate of residential
      posttraumatic stress disorder treatment programs.
AB  - This study utilized a comprehensive assessment of program structure, content, and
      social climate to determine whether specialized residential posttraumatic stress
      disorder (PTSD) programs (SIPUs, n = 19) can be differentiated from general
      psychiatric units (GPUs, n = 18) within the Department of Veterans Affairs.
      Significant differences between program types were found: SIPUs were more clearly
      differentiated from the larger hospital system, had more strict patient selection
      criteria and program regulations, longer length of stays and lower admission
      rates, and spent more program time on PTSD symptoms and war zone experiences than
      GPUs. Veterans in the SIPUs (n = 453) rated the programs significantly higher on
      most social climate measures than veterans with PTSD in the GPUs (n = 153),
      indicating that veterans perceived these programs as more active, supportive, and
      better structured.

PMID- 9246644
TI  - The modular organization of multifunctional peptide synthetases.
AB  - Gramicidin S synthetase 2 from B. brevis was affinity labeled at its valine
      thiolation center with the thiol reagent N-[3H]ethylmaleimide. From a tryptic
      digest of the enzyme-inhibitor complex a radioactive fragment was isolated in
      pure form by two reversed-phase HPLC steps. It was identified by liquid-phase N
      terminal sequencing in combination with electrospray mass spectrometry (ESI-MS)
      as a hexadecapeptide containing the thiolation motif LGG(H/D)S(L/I). By ESI-MS it
      was demonstrated that a 4'-phosphopantetheine cofactor was attached to this
      fragment at its reactive serine. These results are consistent with the "Multiple
      Carrier Model" of nonribosomal peptide biosynthesis. Site-specific mutagenesis
      has been performed in thiolation, elongation, and epimerization motifs of some of
      the modules of surfactin synthetase from B. subtilis to clarify the function of
      prominent conserved amino acid residues in the intermediate steps of peptide
      biosynthesis. The modular structure of multifunctional peptide synthetases is
      discussed.

PMID- 9246646
TI  - Single session effects of treatment components within a specialized inpatient
      posttraumatic stress disorder program.
AB  - This study examined the potential contributions of individual treatment
      components within one inpatient posttraumatic stress disorders (PTSD) program.
      Fifteen treatment components were assessed by a self-report instrument
      administered to a cohort of veterans just before and immediately after each
      session approximately halfway through the program. Components with an external
      focus, action modality, and, secondarily, little Vietnam content were associated
      with more improvement than components with an internal focus, verbal modality, or
      high Vietnam content. Improvement was greatest in veterans with fewer PTSD
      symptoms. Short-term improvement was not correlated with veterans' ratings at
      discharge of component effectiveness. These results were later confirmed on a
      second cohort. This study supports the potential roles of distraction and
      physical release, as opposed to exploratory verbal discussion, in the treatment
      of chronic combat-related PTSD.

PMID- 9246647
TI  - Treatment preferences of Vietnam veterans with posttraumatic stress disorder.
AB  - This study attempted to examine patterns over time in treatment preferences of 65
      veterans who completed a 4 month inpatient posttraumatic stress disorders (PTSD)
      program in order to reveal potentially more beneficial types of treatment.
      Veterans rated the severity of their symptoms and degree of benefit of 35
      different treatment components at discharge, and at 4 and 12 months follow-up.
      Veterans rated their symptoms as having not changed at discharge, and worsening
      by 4 months. Veterans initially perceived components that were high in Vietnam
      content, exploratory in purpose, verbal in modality, and personally focused as
      most effective, but by 12-month follow-up they perceived these as less effective
      than components that were low in Vietnam content, educative, action oriented, and
      externally focused. These effects were strongest among veterans with higher
      levels of PTSD symptomatology. Combat exposure, childhood abuse, and race were
      generally not significant predictors of response. These results underscore the
      importance of further inquiry into the relative value of rehabilitative-oriented
      and psychotherapeutic-oriented treatments for veterans with severe and chronic
      PTSD.

PMID- 9246648
TI  - Inpatient treatment of war-related posttraumatic stress disorder: a 20-year
      perspective.
AB  - These papers show that long-stay inpatient PTSD programs provide treatment that
      is quite different from other programs but that they are neither as effective,
      from a psychometric perspective, nor as helpful, from the veterans' subjective
      perspective, as has been expected. VA treatment of PTSD is changing its focus and
      is being influenced by three distinct societal forces, in addition to data from
      studies like these: (1) the continuing effort of American society to come to
      terms with its Vietnam War experience; (2) the crisis of U.S. health care costs;
      and (3) the emergence of a movement to "re-invent" government and to increase
      public accountability through performance data.

PMID- 9246649
TI  - Discussion: treatment of prolonged posttraumatic stress disorder--learning from
      experience.
AB  - Reports of limited treatment effect in Vietnam veterans with PTSD are discussed.
      Survivors of multiple traumata who suffer from complex PTSD and who live in
      poverty and distress may not properly represent the general case of PTSD. Yet the
      lessons learned suggest that attempts to treat prolonged PTSD by rederessing
      causation are ineffective. The appropriateness of targeting symptoms is also
      challenged. Previously heralded rethorics of healing trauma should be replaced by
      careful assessment of residual disability in a social context. Recognizing
      treatment-resistance in PTSD could lead to favorably investigating interventions
      of modest effect, to shifting from exploration to rehabilitation, and to
      redefining outcome measures such that changes in a variety of domains are
      appreciated.

PMID- 9246650
TI  - An affect-management group for women with posttraumatic stress disorder and
      histories of childhood sexual abuse.
AB  - Systematic research on effective treatment for survivors of childhood sexual
      abuse with posttraumatic stress disorder (PTSD) is virtually non-existent. The
      aim of the present study was to compare the effectiveness of an affect-management
      treatment (AM) group to a wait list control condition for female survivors of
      childhood sexual abuse with PTSD. Forty-eight female survivors of childhood
      sexual abuse with PTSD were randomly assigned to either a 15-week affect
      management treatment group or to a wait list control condition. All subjects
      received individual psychotherapy and pharmacotherapy for the duration of the
      study, and for at least 1-month prior to the study. Controlling for pretreatment
      scores, subjects who completed the affect-management treatment group (n = 17)
      reported significantly fewer posttreatment symptoms of PTSD and dissociation than
      subjects in the wait list control condition (n = 16). Our findings suggest that
      an affect-management group treatment is beneficial as an adjunct to individual
      psychotherapy and pharmacotherapy for survivors of childhood sexual abuse with
      PTSD.

PMID- 9246651
TI  - Posttraumatic stress disorder, self- and interpersonal dysfunction among sexually
      retraumatized women.
AB  - This study assessed self and interpersonal dysfunction as well as posttraumatic
      stress disorder (PTSD) among three groups of women: women sexually assaulted in
      both childhood and adulthood, women sexually assaulted only in adulthood and
      women who were never assaulted. Rates of PTSD were high and equivalent in the two
      assault groups. However, retraumatized women were more likely to be alexithymic,
      show dissociation scores indicating risk for dissociative disorders, and to have
      attempted suicide compared to the other two groups, who did not differ from each
      other. Additionally, only the retraumatized women experienced clinically
      significant levels of interpersonal problems. The findings suggest that
      formulations more inclusive than PTSD are required to capture the psychological
      difficulties experienced by this population. Treatment implications are
      discussed.

PMID- 9246652
TI  - Individual differences in posttraumatic stress disorder symptom profiles in
      Holocaust survivors in concentration camps or in hiding.
AB  - Symptom patterns were compared between Holocaust survivors in concentration camp
      (n = 70) and those who were in "hiding" (n = 30) during the war. The impact of
      age at the time of the trauma, gender, and cumulative lifetime stress, and the
      effect of each of these variables controlling for the others, on posttraumatic
      stress disorder (PTSD) symptoms were also evaluated. A significant negative
      relationship between age at the time of the trauma and symptoms of psychogenic
      amnesia, hypervigilence and emotional detachment, and a positive correlation
      between age and intrusive thoughts, were observed. Cumulative lifetime stress was
      positively associated with symptoms of avoidance. The study provides the first
      empirical data regarding the factors that potentially explain individual
      differences in PTSD symptom patterns in Holocaust survivors.

PMID- 9246653
TI  - Hope, coping, and social support in combat-related posttraumatic stress disorder.
AB  - Dispositional hope, coping, and perceived social support were assessed among
      Vietnam combat veterans upon admission to and discharge from inpatient treatment
      for posttraumatic stress disorder (PTSD). Veterans reported lower dispositional
      hope than any previously described sample, and hope did not increase at discharge
      from treatment. At admission, higher hope was correlated with greater perceived
      social support coming from family (this relationship persisted when controlling
      for depression and PTSD symptoms). At discharge, higher hope was associated with
      greater perceived social support coming from family and friends and the use of
      adaptive coping strategies. Results indicate that hope confers a beneficial
      effect once veterans undergo treatment for combat-related PTSD, a finding that
      suggests that hope may be "gone but not lost" for these individuals.

PMID- 9246654
TI  - The effects of stressor type on projected coping.
AB  - Previous analog research (Bjorck & Cohen, 1993), in which Caucasian college
      students' projected coping responses to major stressors differed as a function of
      stressor type (threat, loss, or challenge), was replicated with an
      ethnoculturally diverse sample. Because Bjorck and Cohen's findings might have
      been confounded by participants' prior life experiences and/or differing
      perceptions of event controllability, these two dimensions were also assessed.
      Even after statistically controlling for these two potential confounds, however,
      projected coping again differed as a function of stressor type. Effects of both
      controllability and prior experience were also found. Results are discussed in
      terms of their application to coping processes in general and to coping with
      trauma in particular.

PMID- 9246655
TI  - Psychometric properties of the Civilian version of the Mississippi PTSD Scale.
AB  - The psychometric properties of the Civilian Mississippi Posttraumatic Stress
      Disorder (PTSD) Scale were explored. The Mississippi is internally consistent
      (alpha approximately = .89, split-half r approximately = .80), and it can
      discriminate between traumatized and nontraumatized respondents. However, its
      relationship with measures of PTSD was weaker than its relationship with measures
      of depression and anxiety, suggesting that it may be more of a general measure of
      distress. The results of a series confirmatory factor analyses provided mixed
      results. These findings were discussed along with recommendations for use of this
      instrument.

PMID- 9246656
TI  - EMDR minus eye movements equals good psychotherapy.
AB  - Eye Movement Desensitization and Reprocessing (EMDR) is a therapy roughly equal
      in efficacy to others currently available. It is argued that this treatment
      method is efficacious independent of the value of its component parts (e.g., eye
      movements) and is successful because it applies common and generally accepted
      principles of psychotherapy. Ten curative principles of this procedure are
      discussed as reflective of sound psychotherapy practice. It is hoped that an
      understanding of this therapy from the perspective of the practice and theory of
      psychotherapy will assist in its study.

PMID- 9246657
TI  - Client compliance with exposure treatments for posttraumatic stress disorder.
AB  - Clients with posttraumatic stress disorder (PTSD) do not wish to "relive" their
      trauma, but exposure based treatments try to ensure that they do. While such
      treatments have proven efficacy in controlled outcome studies, how acceptable are
      they in routine clinical practice? The attempted clinical application of two such
      exposure treatments is briefly reported here. In the first, only 1 of 14 clients
      completed the image habituation procedure for homework in the manner described by
      its authors. In the second (N = 37), only 57% complied with an audiotape exposure
      treatment, and compliance was related to initial symptom severity and to severity
      of comorbid depression. Exposure based treatments are not 'treatment of choice'
      for some clients.

PMID- 9246658
TI  - Leptin in anorexia nervosa and amenorrhea.

PMID- 9246659
TI  - Association studies in psychiatric genetics.

PMID- 9246660
TI  - On the interpretation of association studies in behavioral disorders.

PMID- 9246661
TI  - In defense of genetic association studies.

PMID- 9246662
TI  - Case-control association studies in complex traits--the end of an era?

PMID- 9246663
TI  - Association studies in psychiatry: a season of discontent.

PMID- 9246664
TI  - Genes and the environment in complex diseases: a focus on alcoholism.

PMID- 9246665
TI  - Embryonic limb draws a crowd.

PMID- 9246666
TI  - To be or not to be: Bax provides some answers.

PMID- 9246667
TI  - Possible role of dopamine D1 receptors in schizophrenia.

PMID- 9246668
TI  - What makes the worm squirm?

PMID- 9246669
TI  - Nitric oxide: a spatial second messenger.
AB  - Fast synaptic transmission by excitatory neurotransmitters endows neural tissue
      with remarkable computational power but is limited in its ability to adapt with
      experience. Information in the nervous system can also be distributed beyond the
      synapse by biogenic amines or neuropeptides released at non-synaptic sites to
      elicit volume transmission and by the spatial second messenger nitric oxide which
      can diffuse from a synapse to a volume of surrounding neural tissue. Volume
      transmission and spatial signaling complement classic point-to-point transmission
      and may coordinate local activity among groups of neurons and glia. An
      interesting dialogue exists between these systems. Nitric oxide produced in
      response to excitation of a neuron by glutamate stimulates exocytosis and release
      of glutamate and dopamine from nearby neurons. Dopamine in turn can alter the
      strength of glutamatergic synapses and affect synaptic plasticity.

PMID- 9246670
TI  - Nitric oxide in health and disease of the nervous system.
AB  - Nitric oxide (NO) is a widespread and multifunctional biological messenger
      molecule. It mediates vasodilation of blood vessels, host defence against
      infectious agents and tumors, and neurotransmission of the central and peripheral
      nervous systems. In the nervous system, NO is generated by three nitric oxide
      synthase (NOS) isoforms (neuronal, endothelial and immunologic NOS). Endothelial
      NOS and neuronal NOS are constitutively expressed and activated by elevated
      intracellular calcium, whereas immunologic NOS is inducible with new RNA and
      protein synthesis upon immune stimulation. Neuronal NOS can be transcriptionally
      induced under conditions such as neuronal development and injury. NO may play a
      role not only in physiologic neuronal functions such as neurotransmitter release,
      neural development, regeneration, synaptic plasticity and regulation of gene
      expression but also in a variety of neurological disorders in which excessive
      production of NO leads to neural injury.

PMID- 9246671
TI  - Confirmation of association between attention deficit hyperactivity disorder and
      a dopamine transporter polymorphism.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common condition of
      childhood the symptoms of which include inattention, excessive motor activity,
      inpulsivity and distractibility. It is strongly familial and twin and adoption
      studies suggest that the familiality is due, at least in part, to shared genes.
      Gillis et al found concordance rates in ADHD for MZ and DZ twins of 81% and 29%
      respectively. Stimulant drugs (eg, methylphenidate) are effective in the
      treatment of ADHD and inhibit the dopamine transporter. This has led to the
      development of a hypodopaminergic hypothesis for the disease. Cook et al examined
      a 3' variable number of tandem repeat (VNTR) polymorphism at the dopamine
      transporter gene (DAT1) in a sample of 49 ADHD patients and their parents, using
      the haplotype relative risk (HRR) method. They found a significant association
      (chi 2 = 7.29, 1 d.f., P = 0.007) between ADHD and the 480-bp DAT1 VNTR allele.
      The authors stressed the importance of independent replication and we have
      achieved this in a study of 40 probands and their parents, using the same robust
      HRR method. As in the study of Cook et al we found that the 480-bp allele was
      preferentially transmitted to ADHD probands (chi 2 = 6.07, 1 d.f., P = 0.014).

PMID- 9246672
TI  - 5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D
      binding in globus pallidus but not cortex.
AB  - 5-HT1D and 5-HT1E/1F receptor binding sites were measured in brain samples
      obtained at postmortem from suicide victims with a firm retrospective diagnosis
      of depression, and matched controls. In antidepressant-free suicides a
      significantly higher number of 5-HT1D receptors was found in globus pallidus.
      This was largely restricted to those suicides who died by violent means. This
      effect was not observed in antidepressant-treated suicides. No differences or
      trends in 5-HT1D binding were found in putamen, parietal or frontal cortex, in
      antidepressant-free or antidepressant-treated suicides. There were no differences
      in the number of 5-HT1E/1F receptors in any of the regions studied.

PMID- 9246673
TI  - Chronic haloperidol treatment differentially affects the expression of synaptic
      and neuronal plasticity-associated genes.
AB  - Synaptophysin is a protein used as a marker of presynaptic terminals. We
      previously showed that, in dorsolateral striatum of the rat, 2 weeks' haloperidol
      treatment up-regulated synaptophysin mRNA. We have now investigated the effects
      of 16 weeks' treatment with haloperidol on synaptophysin expression in
      dorsolateral striatum, frontoparietal cortex and hippocampus, in order to see if
      the implied haloperidol-induced synaptic plasticity persists. For comparison, in
      both the 2- and 16-week treatment groups we determined the mRNA abundance of the
      neuronal plasticity-associated gene GAP-43, and the housekeeping gene
      cyclophilin. Sixteen weeks' haloperidol administration increased synaptophysin
      mRNA in striatum and frontoparietal cortex but not in hippocampus. The increase
      was demonstrable both regionally and per neuron. A similar trend was seen for
      synaptophysin protein using immunoautoradiography-GAP-43 mRNA was elevated in
      frontoparietal cortex by 2 weeks' haloperidol but was not significantly changed
      in any area in the 16-week treatment group. Cyclophilin mRNA, a marker of overall
      gene expression, was unaffected by haloperidol. The persistent increase in
      synaptophysin expression supports the evidence that chronic antipsychotic drug
      treatment induces synaptic reorganisation in some striatal and cortical neuron
      populations, whereas the GAP-43 mRNA data suggest that haloperidol does not
      produce a sustained alteration of neuronal plasticity. Further study of
      plasticity-associated gene expression may be valuable in clarifying the long-term
      neuronal and synaptic changes produced by antipsychotics, and how these are
      related to the neurochemical effects of the drugs.

PMID- 9246674
TI  - Leptin levels in patients with anorexia nervosa are reduced in the acute stage
      and elevated upon short-term weight restoration.
AB  - Circulating leptin concentrations are known to be low in acute anorexia nervosa
      (AN), which is characterized by low weight, amenorrhea and specific
      psychopathological features. In this study plasma leptin concentrations were
      determined during inpatient treatment of 23 adolescent females with AN using a
      sensitive radioimmunoassay (RIA) and set into relationship to leptin levels of
      females matched for age, body mass index (BMI; kg m-2) and/or percent body fat.
      At referral patients had leptin concentrations well below the female controls.
      Weight gains led to steep increases of leptin levels which peaked at values well
      in excess of those observed in controls matched for BMI. In patients who reached
      the final treatment stage and who were followed-up after discharge, levels
      subsequently fluctuated and finally dropped into or below the control range. The
      low leptin levels at referral are likely to be involved in the pathogenesis of
      amenorrhea and the reduced metabolic state of acutely ill patients. Peak leptin
      levels reached after weight gain are possibly the cause of increased energy
      expenditure during this stage of the disorder.

PMID- 9246675
TI  - Low leptin levels predict amenorrhea in underweight and eating disordered
      females.
AB  - Evidence that leptin plays an important role in reproductive function is
      accumulating rapidly. We hypothesized that low leptin synthesis is associated
      with amenorrhea. We therefore determined serum leptin levels in 43 underweight
      female students, who were screened for lifetime occurrence of amenorrhea. We
      assessed the predictive value of leptin, body mass index (BMI), fat mass and
      percent body fat, respectively, for lifetime occurrence of amenorrea. Factors
      predicting amenorrhea were tested for their capability to predict current
      amenorrhea in a second cohort of 63 inpatients with anorexia nervosa (AN) or
      bulimia nervosa (BN). Furthermore, the relationships between serum leptin levels
      and of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol
      and progesterone, respectively, were evaluated. Only leptin predicted lifetime
      occurrence of amenorrhea in the student cohort. The critical leptin level was in
      the range of 1.85 micrograms L-1. This level served to largely separate anorectic
      from bulimic patients. In patients with AN mean serum log10 leptin levels over
      the first 4 weeks of inpatient treatment were correlated with mean FSH, LH and
      estradiol levels, respectively. Evidently, a critical leptin level is needed to
      maintain menstruation. In affluent populations eating disorders are likely to be
      a major cause of a low leptin synthesis.

PMID- 9246676
TI  - Apolipoprotein E in progressive supranuclear palsy in Japan.
AB  - Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease which
      shows several psychiatric and neurologic symptoms: pseudobulbar palsy,
      supranuclear ocular palsy, extrapyramidal rigidity, gait ataxia, and dementia.
      Almost all cases seem to be sporadic; therefore, the elucidation of risk factors
      is important to clarify the pathological mechanism. Apolipoprotein E4 (ApoE4) is
      now well established as a risk factor of Alzheimer's disease (AD). Here we report
      the ApoE allele frequency in PSP, which shares pathological findings such as
      neurofibrillary tangle (NFT) with AD. NFT is an important sign for the
      derangement of normal cytoskeletons in degenerating neurons. Although there was
      no significant increase in epsilon 4 allele frequency in the present series of
      PSP cases compared with that in the Japanese controls, there was a significant
      increase in the epsilon 2 allele frequency in PSP compared to controls.

PMID- 9246677
TI  - Antisense strategies in neurobiology.
AB  - The use of antisense oligodeoxynucleotides, targeted to the transcripts encoding
      biologically active proteins in the nervous system, provides a novel and highly
      selective means to further our understanding of the function of these proteins.
      Recent studies of these agents also suggest the possibility of their being used
      therapeutically for a variety of diseases involving neuronal tissue. In this
      paper we review studies showing the in vitro and in vivo effects of antisense
      oligodeoxynucleotides as they relate to neurobiological functions. Particular
      attention is paid to the behavioral and biochemical effects of antisense
      oligodeoxynucleotides directed to the various subtypes of receptors for the
      neurotransmitter dopamine. An example is also provided showing the effects of a
      plasmid vector expressing an antisense RNA targeted to the calmodulin mRNAs in
      the PC12 pheochromocytoma cell line. The advantages of antisense
      oligodeoxynucleotides over traditional pharmacological treatments are assessed,
      and the advantages of using vectors encoding antisense RNA over the use of
      antisense oligodeoxynucleotides are also considered. We also describe the
      criteria that should be used in designing antisense oligodeoxynucleotides and
      several controls that should be employed to assure their specificity of action.

PMID- 9246678
TI  - Critical issues in the antisense inhibition of brain gene expression in vivo:
      experiences targetting the 5-HT1A receptor.
AB  - There have been many recent reports of receptor down-regulation in the brain by
      antisense oligodeoxynucleotides (ODNs) administered in vivo. However, the
      literature is inconsistent regarding the experimental criteria that are necessary
      or sufficient to demonstrate a true antisense effect. Here we review some of the
      critical conceptual and methodological issues. We highlight the problems of
      specificity and toxicity encountered in our attempts to down-regulate the 5-HT1A
      receptor using a phosphorothioate-modified ODN. We also present preliminary data
      suggestive of a decreased hippocampal 5-HT1AR expression induced by the antisense
      ODN, but it is a reduction which is of limited extent and which does not provide
      unequivocal evidence for an antisense-mediated effect. We conclude that antisense
      ODNs are not yet suitable as tools for routine in vivo neuropharmacological use,
      although they show considerable promise.

PMID- 9246679
TI  - Antisense oligonucleotides in neuroendocrinology: enthusiasm and frustration.
AB  - Antisense oligodeoxynucleotides (ODN) offer the potential advantage to manipulate
      neuropeptide or neuropeptide receptor expression within the brain transiently and
      site-specifically, thus providing a tool for neuroendocrinological research into
      the physiological function of a particular neuropeptide system. In this study,
      various approaches are introduced which reveal that antisense ODN may exert
      acute, short-term effects on neuronal responsiveness to afferent stimuli, as well
      as long-term effects on neuropeptide/receptor protein availability in a given
      system depending on the duration of treatment. Short-term effects were seen in
      that oxytocin (OXT) and vasopressin (AVP) antisense ODN affected
      electrophysiological and secretory parameters of oxytocinergic and
      vasopressinergic neurons, respectively, as well as their ability to express the
      Fos protein in response to afferent stimulation a few hours after a single
      infusion into the hypothalamic supraoptic nucleus. In this study, two
      methodological approaches to study long-term effects of the antisense ODN are
      exemplified, in which antisense ODN directed against the mRNA coding for the
      neuropeptide itself or its receptor were used. The repeated infusion of
      corticotropin releasing hormone (CRH) antisense ODN into the paraventricular
      nucleus resulted in reduced immunoreactive CRH, but not AVP, in the external zone
      of the median eminence. Furthermore, in order to evaluate the receptor-mediated
      effects of CRH and AVP released locally within the paraventricular nucleus on
      adrenocorticotropin (ACTH) release from the pituitary, CRH receptor (and also AVP
      receptor) antisense ODN were repeatedly infused into the hypothalamic nuclei;
      this treatment resulted in an elevation of stimulated, but not basal, ACTH
      release into the blood. However, in addition to these obvious antisense effects,
      results are discussed which demonstrate sequence-unspecific effects of
      phosphorothioated ODN, suggesting that some of their mechanisms of action are not
      yet understood.

PMID- 9246680
TI  - Regulation of gene expression by natural antisense RNA transcripts.
AB  - The use of synthetic antisense oligonucleotides as specific inhibitors of gene
      expression exploits the susceptibility of mRNA to functional blockade at several
      levels, including mRNA processing, transport, translation and degradation. It is
      becoming increasingly apparent that the actions of these synthetic oligomers are
      analogous to those of endogenous RNA molecules involved in the regulation of gene
      expression in both prokaryotes and eukaryotes. A growing number of eukaryotic
      genes are now thought to be regulated at least in part by natural antisense RNA
      transcribed from the presumptive non-coding DNA strand. This possibility is
      supported by the presence of a complex system of double-stranded (ds) RNA
      specific proteins and dsRNA-induced signal transduction pathways in eukaryotic
      cells. The presence of functional open reading frames in a number of recognized
      natural antisense RNA transcripts indicates that, in addition to regulating gene
      function at the RNA level, the antisense strand of many genes may code for as yet
      unidentified proteins. In the present study we review the current literature on
      the role(s) played by natural antisense RNA in eukaryotic cells, with an emphasis
      on genes for which clear evidence of regulation, or potential regulation by
      natural antisense RNA is available.

PMID- 9246681
TI  - Uptake and efflux of intact antisense phosphorothioate deoxyoligonucleotide
      directed against angiotensin receptors in bovine adrenal cells.
AB  - Antisense oligonucleotide (AS-ODN) inhibition of angiotensin receptors (AT1-R)
      offers a potentially novel therapeutic approach for hypertension, left
      ventricular hypertrophy and other aspects of cardiovascular disease. To clarify
      questions concerning cellular uptake and retention of these oligos, we quantified
      the trafficking and stability of phosphorothioated modified AS-ODN to AT1
      receptor mRNA in adrenal cells, using visual and chromatographic analysis. The AS
      ODN to AT1 receptor mRNA was effective in significantly inhibiting AT1 receptor
      binding in a dose dependent manner. FITC-labeled ODNs were used to determine the
      cellular uptake in bovine adrena cortex cells; using confocal microscopy, rapid
      cellular uptake of 15-mer ODNs was observed. Uptake is initially rapid (30 min to
      4 h) followed by a slower uptake process 24 h and after. The cellular
      accumulation of ODN involves a dynamic balance between influx and efflux
      processes. Efflux of FITC-ODN had a f1/2 = 4.6 days. Uptake was time and dose
      dependent. No obvious degradation of intracellular ODNs occurred as shown by
      intact peaks for 15-mer ODN on thin layer chromatography. The results suggest
      that the AS-ODN to AT1 receptor mRNA was resistant to cellular nucleases. The
      FITC-ODN accumulated mainly in the nucleus and remained there intact for up to 3
      days. No significant change in target mRNA was observed by quantitative RT-PCR.
      Therefore the antisense inhibition mechanism of this ODN does not appear to
      stimulate RNase H or block transcription. Since the ODN accesses the nucleus, the
      results imply that the ODN inhibits specific mRNA transport into the cytoplasm.
      The data show that AS-ODN, for inhibition of AT1 receptors, is rapidly taken up
      and stable in cells and produces specific inhibition of AT1 receptors.

PMID- 9246682
TI  - A novel fluorescent tag for labelling of some antisense oligonucleotides.
AB  - A new versatile fluorescent tag, 4-acetylamino-1,8-naphthalimido-N-caproic acid
      (NCA) has been synthesized and characterized, and the optimal conditions for the
      maximum fluorescence using this tag allow a sensitivity level of 10(-9) mol/l.
      Useful fluorescence is observed upon covalent linking of this tag via its
      activated carboxy end to an alkylamino moiety, activated by the use of
      carbonyldiimidazole and hexamethylenediamine at the 5'-termini of an octamer,
      d(TCTTGCTC), a 33-mer, and a 41-mer complementary to the tat initiator of the HIV
      1 genome. A new method for the generation of alkylamino function at the 5'
      termini of oligonucleotides by the use of N-(4-bromobutyl) phthalimide is also
      described. The variation in fluorescence with respect to alteration of chain
      length of the oligonucleotides has also been studied. The fluorescence exhibited
      by these oligodeoxynucleotide (ODN)-NCA conjugates suggests that they may have a
      potential application as experimental tools in medicine and molecular biology.

PMID- 9246683
TI  - Pharmacokinetics of antisense analogues in the central nervous system.
AB  - A thorough evaluation of the pharmacokinetical properties of
      oligodeoxyribonucleotides (ODN) is a first step towards their rational
      application as gene expression blockers in the central nervous system (CNS). In
      this paper we present our own data, as well as those of other authors, on tissue
      distribution, stability, retention and cellular uptake of phosphodiester,
      phosphorothioate, and end-capped analogues of ODN introduced into the CNS. ODN
      are easily distributed within nervous tissue, and their tissue penetration
      depends on anatomical conditions. Retention of radioactivity delivered with ODN
      within nervous tissue is higher for phosphodiesters than for phosphorothioates.
      On the other hand, the tissue stability of phosphorothioates is substantially
      greater than the tissue stability of phosphodiesters as well as that of end
      capped ODN. If the elimination process of ODN is also due to their degradation,
      it is apparently accomplished by endonucleases, because the recovery of end
      capped ODN (resistant to exonucleases) was similar to unprotected
      phosphodiesters. The uptake of ODN by nerve cells is rather poor, although we
      have shown that phosphorothioates at least can be internalized by nerve cells in
      vivo. ODN are metabolized by nerve cells, which results in the formation of
      unidentified molecules of higher molecular weight than ODN themselves.

PMID- 9246684
TI  - On the role of c-fos expression in striatal transmission. The antisense
      oligonucleotide approach.
AB  - The antisense oligonucleotide approach has been established as a tool to analyse
      the functional role of c-fos gene expression in the striatum. Studies on the
      distribution and cellular localization of microinjected oligonucleotides, as well
      as their effect on gene expression, demonstrate that the action of the c-fos
      oligonucleotides can be used to evaluate the role of c-fos gene expression
      selectively in neuronal function. Antisense oligonucleotides to c-fos inhibit
      both basal and stimulated c-fos expression in the striatum, which leads to
      characteristic changes in behavioural and biochemical parameters, as evaluated by
      analysis of rotational behaviour and dual probe in vivo microdialysis for the
      neurotransmitter GABA, respectively. These observations could be explained by a
      postulated D1/NMDA receptor interaction in the striatonigral GABA pathway
      controlled by the immediate early gene c-fos. We concluded that c-fos might be
      involved not only in the control of long-term changes in the cellular phenotype
      but also in control of firing rate.

PMID- 9246685
TI  - The use of in vivo antisense oligonucleotide technology for the investigation of
      brain GABA receptors.
AB  - Antisense oligodeoxynucleotides (ODN) can be used as selective inhibitors of in
      vivo gene expression in the central nervous system (CNS) of experimental animals.
      The gamma-aminobutyric acid type A (GABAA) receptor is a member of the ligand
      gated ion channel superfamily of neurotransmitter receptors. GABAA receptor
      function is allosterically modulated by several clinically important compounds,
      e.g. 1,4-benzodiazepines, barbiturates and certain neurosteroids, which recognize
      binding sites within the receptor complex. GABAA receptor chloride channel
      complexes are probably pentamers of different polypeptide subunits. The number of
      known subunit families and isoforms (six alpha s, four beta s, three gamma s, one
      delta and two rho s) indicates an extensive heterogeneity of GABAA receptors. The
      gamma 2 subunit is a functionally integral part of the GABAA receptor, necessary
      for the high affinity binding of benzodiazepines. The infusion of
      phosphorothioate ODN antisense to the gamma 2 subunit mRNA, but not control sense
      or mismatch ODN, into the lateral cerebral ventricle or into the hippocampus of
      rats leads to significant decreases in benzodiazepine receptor radioligand
      binding. In the hippocampus this is accompanied by a decrease in the number of
      GABAA receptors and by a loss of neurones, the latter possibly being due to
      reduced GABAergic inhibitory neurotransmission. Autoradiographic analysis
      following continuous intrahippocampal infusion of antisense ODN shows the
      regional extent of the effect on [3H]flunitrazepam binding. The continuous
      infusion of antisense ODN, but not of mismatch control ODN, into the right
      lateral cerebral ventricle induced a significant decrease in benzodiazepine
      binding and [3H]muscimol binding to membranes of the right cortex. Antisense ODN
      infused into the striatum decreased benzodiazepine binding and binding to the
      GABA binding site of the GABAA receptor to an extent similar to that found in the
      hippocampus. It is concluded that the preferred route of administration of
      antisense ODN for in vivo studies of the GABAA receptor may be by infusion into
      defined rat brain regions. The reported data support the idea that antisense ODN
      can be used as a valuable tool for the investigation of the contribution of
      individual GABAA receptor subunits to the properties of the receptor complex and
      of mechanisms of receptor subunit assembly.

PMID- 9246686
TI  - Effect of dystrophin antisense oligonucleotides on cultured human neurons.
AB  - Antisense oligonucleotides offer the potential to block the expression of
      specific molecules within the cell, thus providing a useful tool in cell function
      studies. In this paper, we tested the possibility to block dystrophin expression
      in in vitro cultured neurons with antisense oligonucleotides administration.
      Human fetal neuronal cultures were treated with different doses of antisense
      oligonucleotides against dystrophin, the protein coded by the Duchenne muscular
      dystrophy gene. Results showed that labelled oligonucleotides rapidly accumulated
      into cultured neurons, but were discarded 15-24 h after treatment. However, no
      effects could be observed until 3-4 days after treatment, when immunocytochemical
      staining for dystrophin was significantly decreased in treated neurons. This
      result was confirmed by polymerase chain reaction assay which showed a
      significantly lower expression of the dystrophin specific mRNA. Electron
      microscope observations confirmed that neurons were affected. Large inclusions or
      packed granules were detectable in their cytoplasm and in terminal endings.
      Neuronal nuclear membrane was sometimes shredded, so that nuclear shape was
      altered. These phenomena were dose-dependent, further substantiating the
      hypothesis of a specific effect of antisense treatment. This interpretation was
      supported by the absence of alterations when cultures were treated with mismatch
      or non specific antisenses. Since the function of dystrophin is still unknown,
      these data might help in understanding the role played by this protein in the
      developing brain.

PMID- 9246687
TI  - Putative roles for the inducible transcription factor c-fos in the central
      nervous system: studies with antisense oligonucleotides.
AB  - Although immediate-early genes such as c-fos are widely believed to play an
      important role in neuroplasticity, there is limited evidence to support
      involvement in the initiation of molecular events leading to medium- and long
      term changes in brain function following a stimulus. Results using techniques
      such as transgenic knockout of the gene are often difficult to interpret.
      Antisense oligonucleotide technology offers an alternative. Infusion of antisense
      oligonucleotide to modify the expression of c-fos in the brain results in
      dramatic changes in rotation behaviour in animals challenged with psychostimulant
      drugs such as amphetamine. Similarly, the knockdown of c-fos expression using
      antisense oligonucleotides can also alter the rate of amygdala kindling in
      response to electrical stimulation of the brain. While studies using antisense
      oligonucleotides to knockdown c-fos expression provide evidence that the
      expression of c-fos plays an important role in regulating neuronal function, the
      use of antisense nucleotides has limitations and experiments must be very
      carefully controlled. Many details of antisense oligonucleotide actions remain
      unknown.

PMID- 9246688
TI  - Fumes from the spleen.

PMID- 9246689
TI  - Utilisation of prenatal services and birth outcomes: a community-based study in
      Israel.
AB  - The purpose of this paper was to assess several measures of utilisation of
      prenatal care as predictors of birth outcome in a community where the
      availability and quality of services were equal for all pregnant women. A case
      control study was conducted in a small community in Israel, comparing 189 women
      whose pregnancy resulted in an unfavourable outcome (perinatal mortality, preterm
      birth and low birthweight at term) with 384 women, matched by birth order, who
      had a live, full-term infant weighing 2500 g or more. In a multivariable
      analysis, adjusting for pregnancy complications, maternal age, parity and socio
      economic disadvantage, gestational age at initiation of prenatal care was not an
      independent predictor of unfavourable outcome; neither was lower than the
      recommended number of visits for the period under care. However, a higher than
      expected number of visits was associated with unfavourable outcome [odds ratio
      (OR) = 6.10, 95% CI 2.09-17.78], as was non-compliance with medical
      recommendations [OR = 2.02, 95% CI 1.24-3.29. The context of prenatal care
      delivery, as well as the process of care and compliance with recommendations,
      should be assessed in order to determine the impact of prenatal care on birth
      outcomes.

PMID- 9246690
TI  - Factors associated with term low birthweight in Cardiff, Wales.
AB  - This project was undertaken to examine the associations of a number of risk
      factors with impaired fetal growth, exemplified by delivery of a low-birthweight
      infant at term (TLBW). Utilising a large database of largely homogeneous (white)
      births in Wales, the Cardiff Births Survey, multivariable analysis by logistic
      regression examined the relative importance of these risk variables. Significant
      independent associations with TLBW were found (in decreasing order of magnitude)
      for low maternal weight, pre-eclampsia, smoking, short maternal height, late
      pregnancy bleeding, early pregnancy bleeding, history of a previous stillbirth,
      primiparity and older maternal age. In this population, risk of TBLW was
      associated with a number of demographic, medical and social factors. Of these,
      only smoking is likely to be modified by intervention.

PMID- 9246691
TI  - Ecological and individual predictors of birthweight in a northern Finland birth
      cohort 1986.
AB  - This multilevel study of spatial variability in, and determinants of, birthweight
      was conducted using individual and ecological data in a geographically defined
      prospective birth cohort for 1986 in northern Finland. The study area comprises
      three large areas defined by latitude: Northern Lapland (NL), Southern Lapland
      (SL) and Oulu province (OP), comprising 74 localities with a total study
      population of 9216 singleton births. The mean birthweight was 3482 g for NL, 3537
      g for SL and 3587 g for OP (NL vs. OP and SL vs. OP: P < 0.05). The crude rate
      for stillbirths was highest in NL. The women in the northernmost area were
      socially less privileged and the localities less prosperous compared with those
      in the southernmost area. Significant spatial clustering of mean birthweights was
      found (P = 0.0016), with highest birthweight in the south-western part of the
      study area. A variable expressing the wealth of each locality, the financial
      capacity category (FCC), had its lowest mean value in NL, with a range of one to
      six for the localities studied here. A multilevel multiple regression model
      showed that, after allowing for sex, gestational age, mother's age, height and
      hypertensive disorders, parity, body mass index, previous low birthweight child
      and smoking as individual determinants of birthweight, part of the residual
      variation could be explained by the locality wealth parameter. Using the
      multilevel model, the differences in mean birthweight across the three latitude
      areas persisted but were reduced (difference OP vs. NL reduced from 105 g to 86.5
      g). The relationship between birthweight and FCC was inverse U-shaped with the
      highest mean birthweight estimated for localities occurring in the middle of the
      range (FCC = 3). The wealthiest urban localities (FCC = 6) and the most deprived
      localities (FCC = 1) both had a predicted birthweight about 60 g below the
      maximum at FCC = 3, if all other factors were held constant. This result, taken
      together with the spatial clustering of birthweights, suggests that there may be
      important social and environmental determinants of birthweight that have yet to
      be identified.

PMID- 9246692
TI  - Assessment of gestational age using birth certificate data compared with medical
      record data.
AB  - We assessed the extent to which use of medical record data might improve
      gestational age estimates compared with reliance on the birth certificate alone.
      Using population-based data from four northern Californian counties, we
      constructed an algorithm to select the best gestational age estimate from
      antenatal assessments recorded in medical records. A total of 172 singletons with
      moderate or severe congenital cerebral palsy from the California Cerebral Palsy
      Project were compared with 472 randomly selected controls with regard to
      discrepancies between the algorithm-derived estimated gestational age (bestgest)
      and an estimate based solely on the last menstrual period as recorded on birth
      certificates. Agreement between bestgest and birth certificate estimated
      gestational age was exact or within one week for at least 60% of both cases and
      controls in each of the three birthweight strata. In general, the greater the
      birthweight of the babies, the better the agreement. The mean number of weeks of
      overestimation by the birth certificate was 0.7 weeks for cases and 1.1 weeks for
      controls in the lowest birthweight group (< 1500 g). When compared with bestgest,
      clinical examination of the infant also tended to overestimate gestational age.
      In the < 1500 g birthweight group, cases were twice as likely as controls to have
      a bestgest of 'low certainty,' but antenatal estimates of 'high certainty' were
      obtained for at least a third of very low birthweight babies born during the mid
      1980s. More widespread use of early ultrasound in more recent birth cohorts may
      result in a greater proportion of accurate antenatal estimates. When a
      distinction between immaturity and intrauterine growth retardation is important
      to the understanding of the aetiology of the outcome under investigation, the use
      of antenatal estimates from medical records may substantially improve the
      certainty of the data.

PMID- 9246694
TI  - Sociodemographic and educational correlates of hearing loss in Hispanic children.
AB  - Sociodemographic and educational correlates of hearing loss were examined in
      Cuban-American, Mexican-American and Puerto Rican children 6-19 years of age.
      Logistic regression analyses indicated a greater risk of bilateral hearing loss
      among children living in crowded housing conditions or without health insurance,
      as well as among those who were below expected school grade level and whose
      parents reported low educational attainment levels. However, the strengths of
      these associations were small to moderate in magnitude and were not always
      consistent across the ethnic subgroups. These findings provide some evidence that
      hearing-impaired Hispanic children are more likely to reside in economically
      disadvantaged families and to be below their expected school grade level.

PMID- 9246693
TI  - Socio-economic deprivation associated with acute rheumatic fever. A hospital
      based case-control study in Bangladesh.
AB  - There are few studies on the relationship between socio-economic factors and
      rheumatic fever (RF) in the populations where the burden of both socio-economic
      deprivation and RF is still very high. The aim of this study is to assess the
      association between some socio-economic factors and RF by examining data
      available from a RF hospital in Bangladesh. We have reviewed the medical records
      of patients presenting with manifestations suggestive of RF during a 1-year
      period. From the patients who showed group A beta-haemolytic streptococcal upper
      respiratory infection (ABHS infection), 44 RF cases defined by the Jones criteria
      and 86 control subjects, who did not satisfy the criteria, were identified for
      analysis. The median age was 12 years and 60% were female. RF was significantly
      associated with low income (odds ratio [OR] 2.37; P = 0.04); poor living
      conditions: substandard (kacha) house (OR 2.93, P = 0.02); and poor nutritional
      status: low height for age (OR 2.68, P = 0.02). Multiple logistic regression
      analysis revealed an increased OR for kacha house (OR 3.18, P = 0.02) but the
      same estimate for low height for age (OR 2.68; P = 0.04). Our analysis shows
      that, among the patients presenting to the RF hospital with proven ABHS
      infection, acute RF is associated with socio-economic deprivation.

PMID- 9246695
TI  - Recruitment, retention and characteristics of women in a prospective study of
      preconceptional risks to reproductive outcomes: experience of the Diana Project.
AB  - Preterm delivery, low birthweight, and intrauterine growth retardation are common
      and recalcitrant problems in many countries. Although much remains to be learned,
      we know particularly little about the relationships between preconceptional and
      early pregnancy exposures and these and other reproductive outcomes. The study
      presented here was primarily designed to investigate the relationships between
      nutritional exposures measured before and during pregnancy and reproductive
      outcomes. This paper describes methods used to recruit the required 1000
      preconceptional women from the collaborating health maintenance organisation
      (HMO) and the retention of participants in this time-intensive study. The results
      presented demonstrate that an adequate completion rate (66.3%), and a remarkably
      representative sample of women that poses few threats to the study's validity,
      can be obtained by population-based recruitment of women from an HMO.

PMID- 9246697
TI  - Demands for all-out rescue.

PMID- 9246696
TI  - The organisation of a national survey for evaluating child psychomotor
      development in Argentina.
AB  - A total of 211 selected paediatricians were invited to participate in a national
      survey designed to evaluate the age of attainment of developmental milestones in
      children aged 0-5 years. Following a pilot study and a cascade training design,
      61.1% of the paediatricians successfully completed the data collection on 139
      developmental items. In the pilot study, there were more missing (not performed)
      items in children over one year of age, thus confirming the impression that
      paediatricians are more familiar with evaluating development in infants. However,
      in the age range 1-5 years, there were significantly fewer missing items in the
      gross motor area than in the other areas. Following a training programme and data
      editing and cleaning, a final sample of 3573 healthy, normal children was
      obtained. The impact of the training process was significant, in the sense that
      3.5% of the items in children older than one year were not performed by the
      paediatricians before training, but this percentage was reduced to 1.9% after
      training (P < 0.01). The sample formed 0.11% of the national population less than
      6 years of age and included a sex ratio of 1.01 compared with a national ratio of
      1.02. There were no significant differences in the geographical distribution of
      the sample in comparison with that of the national population. The social
      composition, assessed by maternal education level, was biased towards a better
      education level than the national population. Mean Z-scores for height and weight
      were not significantly different from zero, when calculated on the basis of the
      national growth standards. In addition to successfully obtaining a representative
      sample for the analysis of the age of attainment of developmental milestones in
      Argentinian children, the survey also accomplished an educational objective in
      the training of paediatricians in developmental paediatrics.

PMID- 9246698
TI  - Does acute alcoholic pancreatitis exist without preexisting chronic pancreatitis?

PMID- 9246699
TI  - Maintenance treatment for gastro-oesophageal reflux disease. A placebo-controlled
      evaluation of 10 milligrams omeprazole once daily in general practice.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a frequent cause for
      consultation in general practice and is a chronically relapsing disease. METHODS:
      This general practice study was a 6-month randomized, double-blind parallel-group
      placebo-controlled assessment of the efficacy and safety of continuous treatment
      with 10 mg omeprazole every morning after initial symptom control in 495 patients
      with GORD but without erosive oesophagitis. RESULTS: On the basis of life-table
      estimates for cumulative relapse rates, patients in the placebo group (52%) were
      almost twice as likely as those in the omeprazole group (27%) to discontinue
      therapy before 24 weeks because of inadequate relief of heartburn or for other
      reasons including adverse events (all-patients-treated analysis, log rank test, P
      = 0.0001). CONCLUSIONS: This study has shown that 10 mg omeprazole once daily is
      an effective and well-tolerated treatment strategy in general practice for the
      long-term management of symptoms of GORD in patients without erosive
      oesophagitis.

PMID- 9246700
TI  - Protoporphyrin-IX distribution and photodynamic effect in rat oesophagus after
      aminolaevulinic acid administration.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a method for local and selective tumour
      destruction achieved by the action of light on a photosensitizing drug. METHODS:
      We investigated the distribution of 5-amino-laevulinic acid (ALA)-induced
      protoporphyrin-IX fluorescence in rat oesophagus by fluorescence microscopic
      examination and then studied the effects of PDT. RESULTS: The highest level of
      fluorescence was achieved in the mucosa after 4 h of 300 mg/kg ALA
      administration. A clear difference in fluorescence between mucosa and muscularis
      was found in all samples except those taken 24 h after ALA administration. PDT
      with ALA caused destruction of the mucosal and, partly, submucosal layers of the
      oesophagus without damaging the muscularis layer. CONCLUSIONS: According to our
      results with microscopic fluorescence kinetics and the preliminary results of
      PDT, selective destruction of the superficial layer of the rat oesophagus is
      achieved with PDT after ALA administration.

PMID- 9246701
TI  - Induction of tumor necrosis factor-alpha and apoptosis in gastric mucosal injury
      by indomethacin: effect of omeprazole and ebrotidine.
AB  - BACKGROUND: The gastric injury associated with nonsteroidal anti-inflammatory
      drug (NSAID) therapy has been linked to the detrimental effects of the agents on
      the processes of prostaglandin generation, leukocyte adherence, superoxides
      production, and mucosal cell proliferation. In the present study we investigated
      the expression of tumor necrosis factor-alpha (TNF-alpha) and epithelial cell
      apoptosis during indomethacin-induced gastric mucosal injury and evaluated the
      effect of two antiulcer agents on this process. METHODS: The experiments were
      carried out with groups of rats subjected to intragastric pretreatment with 40
      mg/kg omeprazole, 100 mg/kg ebrotidine, or vehicle, followed 30 min later by an
      intragastric dose of indomethacin at 60 mg/kg. After 2 h the animals were killed,
      and the gastric mucosal tissue used for macroscopic damage assessment,
      quantitation of TNF-alpha expression, and the assay of epithelial cell apoptosis.
      RESULTS: In the absence of antiulcer drugs, indomethacin caused extensive
      multiple hemorrhagic lesions accompanied by a 47% increase in mucosal expression
      of TNF-alpha and a dramatic (> 300-fold) enhancement in gastric epithelial cell
      apoptosis. Pretreatment with a proton pump inhibitor, omeprazole, produced only
      marginal (6-8%) reduction in the extent of mucosal damage caused by indomethacin,
      whereas the mucosal expression of TNF-alpha decreased by 15% and the apoptotic
      DNA fragmentation by 10-13%. In contrast, the H2-receptor antagonist ebrotidine,
      also known for its gastroprotective effects, not only successfully prevented
      (98.3%) the enhancement in mucosal TNF-alpha expression caused by indomethacin
      but also caused a 54% reduction in the epithelial cell apoptosis. These effects
      of ebrotidine were, furthermore, reflected in a 90.2% prevention in the gastric
      mucosal damage. CONCLUSIONS: Our findings provide new insights into the mechanism
      of gastric injury caused by NSAIDs and show that ebrotidine protection against
      indomethacin-induced mucosal damage occurs through the inhibition of epithelial
      cell apoptosis triggered by the enhancement in the mucosal TNF-alpha expression.
      Our data also show that omeprazole does not possess antiapoptotic properties.

PMID- 9246702
TI  - Unhealed duodenal ulcers despite Helicobacter pylori eradication.
AB  - BACKGROUND: Our aims were 1) to study the influence of several factors (age, sex,
      smoking, previous ulcer disease, ulcer size, chronic gastritis, serum gastrin and
      pepsinogen I levels, therapy regimen and, especially, eradication of Helicobacter
      pylori) on duodenal ulcer healing; 2) to evaluate the frequency of duodenal ulcer
      healing failure despite eradication of H. pylori, to study why this failure
      occurs, and to verify its evolution without antisecretory therapy; and 3) to
      confirm whether a week's prescription of omeprazole is sufficient to obtain ulcer
      healing. METHODS: Three-hundred and eight patients (mean age, 45 +/- 13 years;
      71% males) with duodenal ulcer and H. pylori infection were studied
      prospectively. Biopsy specimens were obtained at initial endoscopy, and serum
      gastrin and pepsinogen I levels were measured. A repeat endoscopy (with biopsies)
      was performed 1 month after eradication therapy had been completed, and a 13C
      urea breath test was also carried out. Three eradication therapies were used:
      omeprazole plus amoxycillin for 2 weeks (OA group, n = 61); 'classic' triple
      therapy (with bismuth; CTT group, n = 65); and 'new' triple therapies for 1 week
      (NTT group, n = 182): omeprazole plus two of the following antibiotics:
      clarithromycin, metronidazole, and amoxycillin. When the ulcer did not heal
      despite successful H. pylori eradication, antacids were prescribed on an as
      needed basis, and endoscopy was repeated 1 month later (2nd control endoscopy).
      If the ulcer was still present, the acid output (basal and pentagastrin
      stimulated) was measured, a secretin test was performed, and a final endoscopy
      (3rd control endoscopy) was carried out after an additional month. The
      statistical method used was multiple logistic regression. RESULTS: Overall
      eradication was achieved in 69% (n = 212) of the patients, and ulcer healing in
      76% (n = 233): 57% in the OA group, 80% in the CTT group, and 81% in the NTT
      group (P < 0.01 when comparing the OA group with the others). Ulcer healing was
      achieved in 90% of H. pylori-eradicated patients and in only 45% of patients with
      eradication therapy failure (P < 0.001). Similar results were obtained when only
      patients treated with NTT were considered: ulcer healing in 90% of patients with
      the organisms eradicated. Eradication of H. pylori (odds ratio (OR), 11.8; 95%
      confidence interval (CI), 6.3-22) and sex (OR, 2.5; 95% CI, 1.2-5.1) were the
      only variables that correlated with ulcer healing in the multivariate analysis.
      The ulcer persisted despite successful eradication of H. pylori in 22 patients.
      The duodenal ulcer had healed spontaneously in 73% of these patients at the 2nd
      control endoscopy. Finally, by the 3rd control endoscopy, only three patients
      still had duodenal ulcer. Therefore, ulcer healing was finally achieved in 98.1%
      (95-99%) of patients in whom H. pylori was eradicated. Gastrin, pepsinogen I,
      acid output, and the secretin test had normal values in all patients.
      CONCLUSIONS: Eradication of H. pylori favours ulcer healing, which is achieved in
      most patients in whom the organism is eradicated. Just 1 week of omeprazole
      therapy (that is, the antibiotic administration period in the new triple
      therapies) is enough to obtain a high ulcer healing rate. Most duodenal ulcers
      that do not heal initially despite H. pylori eradication will ultimately do so
      after several weeks without additional therapy.

PMID- 9246703
TI  - Relationship of cigarette smoking, alcohol use, and dietary habits with
      Helicobacter pylori infection in Japanese men.
AB  - BACKGROUND: Little is known of factors determining infection with Helicobacter
      pylori. METHODS: In a cross-sectional study of 566 men aged 50-55 years, who
      received a preretirement health examination at the Self Defense Forces Fukuoka
      Hospital between January 1993 and December 1994, we examined the association of
      smoking, alcohol use, and dietary habits with H. pylori infection. RESULTS: The
      overall seropositivity as determined with IgG antibody was 79.3% (449 of 566).
      The rank was inversely associated with the infection (trend, P = 0.048). Neither
      smoking nor alcohol drinking was related to the infection. The prevalence
      adjusted for rank tended to be lower in men consuming raw vegetables (trend, P =
      0.12) daily than those with less consumption. Unexpectedly, the consumption of
      tofu (soybean curd) was significantly, negatively related to the infection
      (trend, P = 0.013). The seropositivity was unrelated to the consumption of
      pickled vegetables, soy paste soup, green tea, or garlic. CONCLUSION: The
      findings suggest that fresh vegetables may be protective against H. pylori
      infection. The study does not support either an increased risk of the infection
      associated with salty foods or a protective effect of green tea or garlic.

PMID- 9246704
TI  - Helicobacter pylori inhibits the secretory activity of gastric parietal cells in
      patients with chronic gastritis. An ultrastructural study.
AB  - BACKGROUND: Previous in vitro studies suggested that Helicobacter pylori may
      inhibit the acid secretion of gastric parietal cells. The aim of this study was
      to investigate ultrastructurally the influence of H. pylori infection on the
      gastric parietal cell function in vivo. METHODS: This study comprised 28 patients
      with chronic gastritis. Biopsy specimens were taken from the gastric body in all
      cases and examined by electron microscopy. Gastric parietal cells were counted in
      each ultrathin section and classified into secretory and non-secretory types. The
      pH of the gastric juice was also measured in all patients. RESULTS: The number of
      parietal cells in the secretory phase was significantly lower in H. pylori
      infected (n = 16) patients than in those (n = 12) without H. pylori infection.
      The intragastric pH was significantly higher in patients with H. pylori
      associated gastritis than in those without H. pylori infection. Parietal cells in
      secretory phase tended to decrease in proportion to the activity of the gastric
      mucosal inflammation. CONCLUSIONS: The results of this investigation suggests
      that H. pylori-associated gastritis is related to a decreased secretory activity
      of the gastric parietal cells.

PMID- 9246705
TI  - Cure of Helicobacter pylori infection improves gastric acid secretion in patients
      with corpus gastritis.
AB  - BACKGROUND: For more than 30 years it has been known that gastric acid secretion
      is inversely related to the extent and severity of corpal gastritis. We therefore
      evaluated the effect of cure of Helicobacter pylori infection on basal and
      pentagastrin-stimulated acid secretion. METHODS: Basal acid output (BAO) and
      maximal acid output (MAO) were assessed in 11 H. pylori-infected dyspeptic
      patients (8 women and 3 men; mean age, 28 years) before and after successful anti
      H. pylori therapy. RESULTS: The gastritis index was significantly lower after
      therapy and was associated with an increase in both BAO and MAO after cure of the
      H. pylori infection (BAO from 0.3 mmol/h and MAO from 4.8 mmol/h to 19 mmol/ h).
      Basal and stimulated acid concentrations also increased (29.1 +/- 36.6 to 54 +/-
      31 mmol/l and 72.5 +/- 46 to 120.1 +/- 30 mmol/l, respectively, for basal and
      stimulated acid concentrations; P < 0.05 for peak and MAO, P = 0.07 for BAO).
      CONCLUSION: Gastric acid secretion increased into the normal range after
      successful treatment of H. pylori infection, suggesting that gastric function can
      recover to normal or almost normal after cure of H. pylori infection.

PMID- 9246706
TI  - Twenty-four-hour basal and repetitive pentagastrin-stimulated gastric acid
      secretion in normal and sham-operated rats and in rats after gonadectomy or
      treatment with estradiol or testosterone.
AB  - BACKGROUND: Studies in different species have suggested, but not established,
      that sex hormones influence gastric acid secretion. We studied how acid output is
      affected by the sex hormones estradiol or testosterone in vivo and in vitro.
      METHODS: In gastric fistula rats that were normal, sham-operated, neonatally
      gonadectomized, or treated with estradiol or testosterone, 24-h basal and
      pentagastrin-stimulated acid secretion was measured. The in vitro effects of
      estradiol and testosterone on histamine-induced aminopyrine accumulation in
      isolated parietal cells were also determined. RESULTS: Basal acid output was
      similar in the two sexes, but stimulated secretion was significantly higher (34%;
      P < 0.01) in males. Ovariectomy did not influence acid output, whereas
      orchidectomy reduced basal (18%; NS) and stimulated 24-h secretion (P < 0.01).
      Estradiol decreased (23%; NS) the 24-h basal output in females but not in males.
      Estradiol suppressed stimulated secretion in females (29%, P < 0.01) and males
      (42%, P < 0.01) during the day. At night the stimulated secretion increased in
      both females (17%, NS) and males (32%, P < 0.05). A similar pattern was found
      when rats were treated with testosterone. In vitro, estradiol and testosterone
      reduced histamine-stimulated aminopyrine accumulation in both female and male
      isolated parietal cells. CONCLUSIONS: Estradiol and testosterone both appear to
      influence gastric secretion in rats, and their action differs between day and
      night, between the sexes, and between basal and stimulated secretion.

PMID- 9246707
TI  - Helicobacter pylori infection and gastric emptying of indigestible solids in
      patients with dysmotility-like dyspepsia.
AB  - BACKGROUND: The role of Helicobacter pylori and gastric motility in dysmotility
      like dyspepsia is unclear. The aim of this study was to determine whether delayed
      gastric emptying of indigestible solids and H. pylori infection are associated
      with dysmotility-like dyspepsia. METHODS: Thirty-two healthy volunteers and 72
      patients fulfilling the criteria of dysmotility-like dyspepsia received a gastric
      emptying test using radiopaque markers, and the H. pylori status was determined
      by histology. RESULTS: Twenty-seven percent of volunteers were H. pylori
      positive, compared with 32% in the dyspeptic groups (P = NS). Gastric emptying
      was significantly slower in dyspeptic patients than controls and in H. pylori
      positive patients than H. pylori-negative patients. Subjects with gastroparesis
      have a higher chance of developing dysmotility-like dyspepsia (odds ratio (OR),
      2.5) than subjects with normal gastric emptying. Subjects with H. pylori and
      gastroparesis have an increased likelihood of developing dysmotility-like
      dyspepsia (OR, 4.3) than if either factor were present alone. CONCLUSION: Our
      data suggest that gastroparesis alone and gastroparesis and H. pylori infection
      are associated with dysmotility-like dyspepsia.

PMID- 9246708
TI  - Antroduodenal manometry in children with no upper gastrointestinal symptoms.
AB  - BACKGROUND: The interpretation of antroduodenal manometry in children with
      gastrointestinal motility disorder has been limited by a paucity of data from
      normal children. The purpose of this study was to define antroduodenal manometry
      findings in children with no upper gastrointestinal symptoms. METHODS: We
      reviewed 260 consecutive antroduodenal manometries and selected 18 studies from
      subjects aged 2-12 years with no symptoms referable to a gastrointestinal
      motility disorder involving the stomach and/or the small bowel. RESULTS: During
      fasting, phase 3 of the migrating motor complex (MMC) was present in 14 of 18
      children, and it was induced by erythromycin in 4 who failed to have a
      spontaneous phase 3. Phase 3 propagation velocity increased significantly with
      age. The cycle length between MMCs showed no age-dependent variation. Phase 3
      occupied 3%; phase 1, 10%; and phase 2, 87% of the fasting recording time.
      CONCLUSIONS: Antroduodenal manometry findings in children with no upper
      gastrointestinal symptoms are similar to those in adults.

PMID- 9246709
TI  - Body composition changes measured by dual-energy X-ray absorptiometry in patients
      receiving home parenteral nutrition.
AB  - BACKGROUND: To monitor changes in body composition in patients receiving home
      parenteral nutrition (HPN) and to ascertain whether changes were related to the
      amount of energy supplied by HPN, we studied prospectively patients with gut
      failure maintained on HPN. METHODS: Patients were subjected to repeated
      measurement of body composition by dual-energy X-ray absorptiometry (DXA), the
      second investigation being performed after a mean period of 20 (range, 11-26)
      months. Thirty-two patients were included, one patient was excluded, and five
      patients died during the study period. At inclusion, the patients had received
      HPN for a mean period of 30 (range, 6-216) months. The indication for HPN was
      inflammatory bowel disease (n = 16), abdominal cancers (n = 5), and scleroderma
      and others (n = 11). The fat-free mass (FFM), fat mass (FM), and total body
      mineral content (TBMC) were measured by DXA. RESULTS: Mean body mass index
      decreased from 21.18 to 20.96 kg/m2 (P = 0.36). The mean FFM showed a small,
      insignificant increase to 37.68 kg (P = 0.71). Mean TBMC was unchanged at 2.28
      kg, and mean FM decreased from 19.25 to 18.17 kg (P = 0.055). During the study
      period the mean daily energy supply by HPN was reduced from kcal 1195 to kcal 959
      (P = 0.004). There was a direct positive correlation between the individual
      changes in HPN energy supply and body weight and FFM (r = 0.437, r = 0.410, P <
      0.05). CONCLUSION: The body composition of HPN patients was stable, with no
      change in mean FFM, FM, or TBMC. Individual changes in body weight and FFM
      correlated with change in HPN energy supply.

PMID- 9246710
TI  - Endogenous prostaglandins and microflora modulate DNA synthesis and
      neuroendocrine peptides in the rat gastrointestinal tract.
AB  - BACKGROUND: Previous studies suggest that E2 prostaglandins and the microflora
      may participate in the regulation of endocrine cells and of gastrointestinal cell
      kinetics. Our aim is to examine the actions of endogenous prostaglandins and of
      the microflora on gastrointestinal cell proliferation and tissue levels of
      neuroendocrine peptides. METHODS: Germfree and ex-germfree rats were treated with
      subcutaneous placebo or 1.5 mg/kg indomethacin for 3 days. All rats were labeled
      with 3H-methyl-thymidine, and biopsy specimens from different parts of the
      gastrointestinal tract were processed for autoradiography. DNA synthesis was
      estimated by the labeling index, except in the oxyntic mucosa, where the total
      number of labeled cells present in 7.5 mm mucosa was used. The concentration of
      neuroendocrine peptides was determined by radioimmunoassay. RESULTS: In the
      germfree rat, indomethacin reduced DNA synthesis in the fundus, duodenum, and
      proximal jejunum (P < 0.05) and the number of villous cells throughout the small
      intestine (P < 0.05). Exposure to microflora increased DNA synthesis in the
      proximal and distal jejunum, ileum, and colon (P < 0.05 versus germfree controls)
      and the number of crypt cells in the distal small intestine and colon (P < 0.05)
      and reduced the number of villous cells in the small intestine (P < 0.05) but did
      not affect tissue concentrations of neuroendocrine peptides. Indomethacin
      increased the concentration of somatostatin in the stomach, duodenum, and colon
      of germfree rats (P < 0.001), the concentration of calcitonin gene-related
      peptide (CGRP) and enteroglucagon in the proximal and distal jejunum and ileum (P
      < 0.001), and the concentration of glucagon in the colon (P < 0.05). The
      concentrations of somatostatin, CGRP, and glucagon were lower in indomethacin
      treated ex-germfree rats than in indomethacin-treated germfree rats (P < 0.01).
      CONCLUSIONS: Indomethacin selectively reduced DNA synthesis in the upper
      gastrointestinal tract of germfree rats, indicating a basal stimulatory role for
      endogenous prostaglandins on cell proliferation. Endogenous prostaglandins
      modulate synthesis or release of gastrointestinal neuroendocrine peptides.
      Somatostatin may mediate indomethacin-induced reduction of DNA synthesis. The
      microflora stimulates cell proliferation and influences tissue levels of
      neuroendocrine peptides in a manner opposite to that of indomethacin.

PMID- 9246711
TI  - Intestinal inflammation and barrier function in HLA-B27/beta 2-microglobulin
      transgenic rats.
AB  - BACKGROUND: Since intestinal inflammation is correlated with impaired barrier
      functions, transgenic HLA-B27/human beta 2-microglobulin rats that spontaneously
      develop intestinal inflammation were used to investigate whether onset of
      inflammation or impaired barrier function was the initial event. METHODS: During
      the age period of 9-14 weeks, transgenic and non-transgenic (control) rats were
      gavaged weekly with the marker molecules, 51Cr-ethylenediaminetetraacetic acid, 1
      deamino-8-D-arginine vasopressin, and albumin, which were quantified in blood or
      urine. RESULTS: At 12 weeks of age the first signs of inflammation appeared with
      decreased body weight gain, decreased urine production, and onset of diarrhea. By
      14-15 weeks of age all transgenic rats had developed intestinal inflammation, as
      confirmed by histology and increased myeloperoxidase content, whereas no
      inflammation was observed in controls. Intestinal passage of the markers did,
      however, not differ between transgenic and control rats over the studied period.
      CONCLUSIONS: The results suggest that intestinal inflammation precedes altered
      intestinal barrier function in this inflammation model.

PMID- 9246712
TI  - Colorectal dysplasia and carcinoma in patients with ulcerative colitis and
      primary sclerosing cholangitis.
AB  - BACKGROUND: The aim of this study was to evaluate the role of primary sclerosing
      cholangitis (PSC) as a cofactor in the dysplasia-carcinoma sequence in ulcerative
      colitis (UC). METHODS: Forty-five patients with UC and concomitant PSC and 45
      pair-matched control patients with UC only were examined for colorectal dysplasia
      and carcinoma. RESULTS: The median duration of UC was 11 years in the group with
      UC and PSC and 15 years in the control group. Thirteen of the 45 patients (29%)
      with UC and PSC had colorectal neoplasia: 4, carcinoma; 2, high-grade dysplasia;
      and 7, low-grade dysplasia. Four of the 45 control patients (9%) had neoplastic
      findings: 1, carcinoma; 1, high-grade dysplasia, and 2, low-grade dysplasia (P <
      0.05). CONCLUSION: The results suggest that the risk of colorectal dysplasia and
      carcinoma in patients with UC is increased by concomitant PSC.

PMID- 9246713
TI  - Low seroprevalence of Helicobacter pylori antibodies in historical sera of
      patients with Crohn's disease.
AB  - BACKGROUND: Our aim was to determine the seroprevalence of Helicobacter pylori
      antibodies in historical sera from a large group of patients with Crohn's disease
      and to compare the findings with those of a control group of healthy blood
      transfusion donors. METHODS: The historical sera from 386 patients with Crohn's
      disease were studied (serum age, 9.9 years; range, 0.4-21.6 years). Serum IgG and
      IgA H. pylori antibodies were measured with enzyme-linked immunosorbent assay.
      Western blots (detecting IgG only) were also used to study a subpopulation of the
      patients' sera and to assess the presence of cagA bands, indicating a cytotoxic
      variety of H. pylori. The serology of the Crohn's disease patients was compared
      with that of 277 age-matched controls. A longitudinal follow-up study of 14 IgG
      and IgA anti-H. pylori-positive and 14 IgG- and IgA-negative Crohn's disease
      patients was also performed (mean follow-up, 7.6 years; range, 1.7-20.5 years).
      RESULTS: Of the total Crohn's disease patients, 47 (12.2%) had IgG antibodies
      against H. pylori, 67 (17.4%) had IgA antibodies, and 31 (8.0%) had both IgG and
      IgA antibodies. The corresponding antibody positivities for the controls were 98
      (35.4%) for IgG, 77 (27.8%) for IgA, and 64 (23.1%) for both IgG and IgA. When
      compared, with the control group, the seroprevalence of H. pylori in the Crohn's
      disease patients was significantly lower (P < or = 0.002). In addition the
      relative IgG response of the patients was lower than the IgA response. The
      opposite was true for the controls. There was no difference in the absolute
      levels of H. pylori antibodies between patients and controls. In the follow-up
      study two patients initially IgG-positive for H. pylori became negative over
      time; these patients had been treated for their infection. the rest, who
      continued to be positive, were not treated. One patient who was initially IgA
      positive also became IgA-negative over time. The follow-up group, who were
      initially IgG- and IgA-negative, remained IgG-negative with time, and two
      patients became IgA-positive. Findings of anti-H. pylori IgG were confirmed with
      Western blots. Furthermore, these showed that of the H. pylori-positive patients
      (indicated by their IgG positivity), 66% were infected with a cytotoxic (cagA
      positive) variety, compared to 69.4% of the controls. CONCLUSIONS: Patients with
      Crohn's disease have a lower prevalence of H. pylori antibodies than an age
      matched control group. There is a reversal of the relative IgG and IgA responses
      in Crohn's disease patients compared with the controls. Of the Crohn's disease
      patients with H. pylori most are infected with cytotoxic varieties, similar to
      controls.

PMID- 9246714
TI  - Variability of gallbladder emptying after oral stimulation.
AB  - BACKGROUND: To date, the intraindividual reproducibility of fasting and
      postprandial gallbladder (GB) volumes has not been established satisfactorily.
      Hence we examined the variability of postprandial GB motility, using the biplane
      Simpson method as a new sonographic tool for GB volume determination. METHODS:
      The biplane Simpson method was validated in vitro and in vivo and compared with
      the sum-of-cylinders method. Thereafter, postprandial GB emptying after a defined
      test meal was examined in 10 healthy volunteers over 108 min on days 1, 31, and
      61. RESULTS: The results of the biplane Simpson method correlated with real
      volumes (r = 0.99) and provided a intra- and inter-observer variation of less
      than 5%. Intraindividually, differences in fasting GB volume ranged from 1.9 to
      24.0 ml within the observation period. The patterns of GB emptying also showed
      fluctuations characterized by a rather large interindividual and intraindividual
      variability. CONCLUSIONS: The biplane Simpson method is a reliable tool for
      measuring GB volumes. The fasting and the postprandial GB volumes vary
      considerably within individuals when measured over a period of 2 months.

PMID- 9246715
TI  - Hemodynamic studies and esophageal morphometric analyses in portal hypertensive
      rats with left adrenal vein ligation.
AB  - BACKGROUND: Despite many attempts to create esophageal varices in experimental
      animals, most of them have failed. This study investigated whether rats with
      partial portal vein ligation (PVL) and left adrenal vein ligation (LAL) develop
      hyperdynamic circulation and dilated esophageal submucosal veins as compared with
      sham-operated (Sham) plus LAL rats. METHODS: Two series of experiments were
      performed to measure (a) systemic and portal hemodynamics and (b) the cross
      sectional area of esophageal submucosal veins in Sham, PVL, Sham plus LAL, and
      PVL plus LAL rats. Hemodynamic studies with a thermodilution technique and
      esophageal morphometric analyses were performed 14 days after the operation.
      RESULTS: PVL rats with or without LAL had a significantly lower mean arterial
      pressure and systemic vascular resistance accompanied by a significantly cardiac
      index and portal pressure than Sham rats with or without LAL (P < 0.05). LAL did
      not induce changes in mean arterial pressure, cardiac index, systemic vascular
      resistance, hear rate, or portal pressure in either Sham or PVL rats (P > 0.05).
      The mean cross-sectional area of esophageal submucosal veins in PVL rats with LAL
      (7340 +/- 833 microns2) was significantly larger than that in Sham rats with LAL
      (4236 +/- 556 microns2; P < 0.05). There was no significant difference in the
      mean cross-sectional area of esophageal submucosal veins between PVL and Sham
      rats without LAL. CONCLUSIONS: PVL rats with LAL developed hyperdynamic
      circulation similar to PVL rats without LAL. In addition, PVL plus LAL rats had
      larger esophageal submucosal veins than Sham plus LAL rats. This study shows that
      the esophageal submucosal veins of the 14-day partially portal vein-ligated rats
      with LAL resemble the structural abnormalities observed in human esophageal
      varices, suggesting that this model could be useful to investigate this entity.

PMID- 9246716
TI  - Relationship between portal pressure, esophageal varices, and variceal bleeding
      on the basis of the stage and cause of cirrhosis.
AB  - BACKGROUND AND METHODS: Hepatic venous pressure gradient, esophageal varices, and
      variceal bleeding were investigated in 957 patients with cirrhosis. The causes
      (alcoholic/virus) and stage (Child-Pugh's classification) of cirrhosis were also
      taken into account. RESULTS: The prevalence of variceal bleeding was 35% in
      patients with large varices and 17% in those with small varices (P < 0.05). It
      was higher in patients with alcoholic cirrhosis (41% and 19%, respectively) than
      in those with viral cirrhosis (22% and 10%, respectively). In patients with
      alcoholic cirrhosis the hepatic venous pressure gradient was higher in Child A
      and B patients with small or large varices than in those with no varices; these
      differences were not found in Child C patients and in patients with viral
      cirrhosis. In all subgroups the pressure gradient was higher in Child C patients
      than in Child A patients. There was no significant difference in the hepatic
      venous pressure gradient between patients with varices and previous variceal
      bleeding and those with no bleeding whatever the stage of cirrhosis. CONCLUSIONS:
      This study shows that the hepatic venous pressure gradient is associated with the
      stage and causes of cirrhosis and the presence of varices. These factors should
      be taken into account in studies evaluating the hepatic venous pressure gradient
      in heterogeneous groups of patients.

PMID- 9246717
TI  - The exudate-transudate definition is dated.

PMID- 9246718
TI  - An old friend in a new home: cadherins at the synapse.

PMID- 9246719
TI  - Rediscovering an old friend, IGF-I: potential use in the treatment of
      neurodegenerative diseases.
AB  - Insulin-like growth factor-I (IGF-I) is a pleiotropic protein that acts on many
      tissues and organs. As it is one of the major trophic factors in the circulation,
      its actions in peripheral tissues are well established. It has been used for the
      treatment of several diseases, including growth deficiency, osteoporosis,
      catabolic disorders and diabetes. Recent evidence supports the significance of
      IGF-I in the maintenance of the integrity and homeostasis of the nervous system.
      The widespread distribution of its receptor allows IGF-I to affect the survival
      of numerous populations of neurones and glial cells in both the CNS and the PNS.
      Most recently, a clinical trial has revealed the beneficial effects of IGF-I in
      amyotrophic lateral-sclerosis (ALS), a degenerative disease of the motoneurones.
      We review briefly here experimental and clinical information that suggests the
      potential usefulness of IGF-I in the treatment of certain neurodegenerative
      diseases, including ALS, Alzheimer's disease, various neuropathies and brain
      trauma. The rather unique propensity of IGF-I to act on a variety of neuronal
      cells might provide a general means of reducing or slowing down neuronal losses
      that occur following various brain insults.

PMID- 9246720
TI  - Neural correlates of key stimulus and releasing mechanism: a case study and two
      concepts.
AB  - Major themes in neuroethology concern the specificity of key stimuli, neurones
      tuned to such stimuli, and the release of corresponding behaviour.
      Neurobiological data from the analysis of visuomotor functions of prey-catching
      and avoiding in amphibians support the view that retinal outflow in different
      combinations is pooled for further computation in interacting processing streams,
      rather than segregated into distinct retinal channels. The keys by which the
      visual system gets access to perceptual-motor categories are shown to derive from
      specific computational strategies that evaluate significant configurational
      features of objects. Rapid behavioural responses are assured by visuomotor
      pathways which, monitoring different aspects of visual objects, collectively
      select appropriate motor patterns. Responses can be adapted to varying
      environmental and internal conditions via modulating and modifying loops. This
      requires parallel distributed processing and integration at various levels in a
      macro-network.

PMID- 9246721
TI  - Schizophrenia as failure of hemispheric dominance for language.
AB  - Schizophrenic illnesses occur with approximately the same incidence in all human
      populations with a characteristic distribution (slightly earlier in males) of
      ages of onset. Given that the predisposition (which presumably is genetic) is
      associated with a procreative disadvantage why do such illnesses persist? Here it
      is suggested that these conditions are a manifestation of genetic diversity in
      the evolution of the specifically human characteristic of language, an innovation
      that has occurred by a process of progressive hemispheric specialization-the
      establishment of dominance for some critical component of language in one or the
      other hemisphere. Individuals who develop schizophrenic symptoms show lesser
      anatomical and functional asymmetries than the population as a whole; such
      symptoms may reflect 'dominance failure' for language.

PMID- 9246722
TI  - How should brain nuclei be delineated? They don't need to be!

PMID- 9246723
TI  - How should brain nuclei be delineated? They don't need to be!

PMID- 9246724
TI  - How should brain nuclei be delineated? They don't need to be!

PMID- 9246725
TI  - How should brain nuclei be delineated? They don't need to be!

PMID- 9246726
TI  - Locomotor recovery after spinal cord injury.

PMID- 9246727
TI  - Lesion-induced network plasticity in remote brain areas.

PMID- 9246728
TI  - Trinucleotide-repeat expansion diseases.

PMID- 9246729
TI  - The TINS Lecture. The parietal association cortex in depth perception and visual
      control of hand action.
AB  - Recent neurophysiological studies in alert monkeys have revealed that the
      parietal association cortex plays a crucial role in depth perception and visually
      guided hand movement. The following five classes of parietal neurons covering
      various aspects of these functions have been identified: (1) depth-selective
      visual-fixation (VF) neurons of the inferior parietal lobule (IPL), representing
      egocentric distance; (2) depth-movement sensitive (DMS) neurons of V5A and the
      ventral intraparietal (VIP) area representing direction of linear movement in 3-D
      space; (3) depth-rotation-sensitive (RS) neurons of V5A and the posterior
      parietal (PP) area representing direction of rotary movement in space; (4)
      visually responsive manipulation-related neurons (visual-dominant or visual-and
      motor type) of the anterior intraparietal (AIP) area, representing 3-D shape or
      orientation (or both) of objects for manipulation; and (5) axis-orientation
      selective (AOS) and surface-orientation-selective (SOS) neurons in the caudal
      intraparietal sulcus (cIPS) sensitive to binocular disparity and representing the
      3-D orientation of the longitudinal axes and flat surfaces, respectively. Some
      AOS and SOS neurons are selective in both orientation and shape. Thus the dorsal
      visual pathway is divided into at least two subsystems, V5A, PP and VIP areas for
      motion vision and V6, LIP and cIPS areas for coding position and 3-D features.
      The cIPS sends the signals of 3-D features of objects to the AIP area, which is
      reciprocally connected to the ventral premotor (F5) area and plays an essential
      role in matching hand orientation and shaping with 3-D objects for manipulation.

PMID- 9246731
TI  - Neuroscience and human intelligence differences.
AB  - Research into the biological bases of human intelligence differences is surveyed.
      Work on brain event-related potentials (ERPs) suggests that people with high IQ
      test scores: (1) show faster responses in some test conditions; (2) have ERP
      waveforms that can be distinguished from those of people with lower IQs; and (3)
      might have less variability in their ERPs. People with higher psychometric
      intelligence have, on average, larger brains, and possibly faster neural
      conduction speed. A few small functional brain-scanning studies suggest that, in
      healthy individuals, people who are of higher IQ have lower cerebral metabolic
      rates during mentally active conditions. This has led to the speculation that
      brighter people have more efficient brains. Despite some well-replicated findings
      in the search for the 'biology of human intelligence' there is a dearth of
      explanatory accounts to link cognitive performance differences with variance in
      brain mechanisms.

PMID- 9246730
TI  - Hematolymphopoietic and inflammatory cytokines in neural development.
AB  - It is now clear that cytokines traditionally viewed as immune modulators
      participate in inflammatory responses within the adult nervous system. However,
      in the developing nervous system hematolymphopoietic cytokines also play a role
      unrelated to neural-immune interactions. Instead, many of these factors subserve
      primary regulatory functions related both to the morphogenesis and to the
      cellular maturation of the central and peripheral nervous systems. This article
      focuses specifically on cytokine actions in neural development.

PMID- 9246732
TI  - Is there any possibility of detecting the use of genetic engineering in processed
      foods?
AB  - To elucidate if there is any possibility to identify highly processed foods as
      produced through genetic engineering, beer, soya bean oil, processed tomato
      (ketch-up, paste, pizza tomatoes, peeled tomatoes, soup) and potato (french
      fries, crisps, mashed potatoes, flour, starch, fried potatoes) products as well
      as an enzyme preparation (Natuphos) were investigated by PCR. In pizza tomatoes,
      peeled tomatoes, french fries, fried potatoes, potato flour and potato crisps DNA
      suitable for PCR was found. Therefore, it is possible to identify these products
      as produced through genetic engineering. Such an identification is impossible in
      certain beers (pilsener, export, Nutfield lyte), soya bean oil, tomato soup,
      potato starch, mashed potatoes and Natuphos since PCR-analysis gave no indication
      of the presence of DNA in these products. As it was shown by adding Escherichia
      coli DNA the used method is, in principle, capable of detecting specifically
      small amounts of DNA in such products.

PMID- 9246733
TI  - Dietary thiamin supply during lactation influences thiamin status in lactating
      rats and their offspring and the thiamin level in milk.
AB  - This study was conducted to examine the effect of dietary thiamin, ranging from
      deficient to excessive supplies, on thiamin status of lactating rats and their
      offspring, and the thiamin level in milk. Therefore, after parturition, rat dams
      were divided into eight groups of 10 each, and were fed diets with 0, 2, 4, 6, 7,
      40, 350 and 3500 mg/kg thiamin over a total of 13 days during lactation. Milk for
      determining the thiamin concentration was obtained from day 6 and 13 of
      lactation. At day 14 of lactation rat dams and their offspring were used to
      ascertain the thiamin status including transketolase activity of blood, liver and
      brain, and thiamin concentration in body. Thiamin supplies ranging from deficient
      to excessive dietary concentrations influenced both the thiamin levels of the
      lactating dams and their offspring within 13 days. Lactating rat dams fed a
      thiamin-free diet and their offspring were classified as thiamin-deficient on the
      basis of growth retardation and a lower activity of transketolase in blood, liver
      and brain. Within these variables transketolase in blood has been shown to be
      most sensitive, and reached a plateau feeding 6 mg/kg thiamin. The concentration
      of thiamin in milk ranged between 0.1 and 19 mg/kg. The findings also show that
      dietary thiamin had the strongest effect on thiamin in milk obtained from day 6
      and 13 of lactation, and a deficient or suboptimal supply with thiamin was
      therefore not compensated for an intensified transfer of reserved body thiamin
      into milk. Also thiamin levels in tissues and carcass, which did not show any
      clear-cut saturation characteristic, increased with increasing dietary thiamin,
      and this dose-dependence was more marked in blood and liver than in carcass.

PMID- 9246734
TI  - Mucin output in ileal digesta of pigs fed a protein-free diet.
AB  - Daily outputs of mucin in ileal digesta were estimated in three barrows fed a
      protein-free diet while administered either saline (SAI) or a complete amino acid
      mixture (AAI) intravenously. The water soluble-ethanol precipitable fraction of
      ileal digesta (crude mucin; CM) was used to estimate the composition of mucin in
      ileal digesta. This fraction exhibited a carbohydrate composition characteristic
      of mucin and had a high threonine, serine and proline content (40 mol/100 mol).
      The proportions of soluble gastric and intestinal mucins, approximately 27 and
      73%, respectively, were estimated from the N-acetylglucosamine (GlcNAc)/N
      acetylgalactosamine (GalNAc) ratio in CM. The daily outputs of soluble mucin,
      2.75 and 3.41 g/day from SAI and AAI pigs (p = 0.13), respectively, were
      determined from the GalNAc outputs in CM, assuming the above contributions of
      gastric and intestinal mucins. The estimated soluble mucin outputs accounted for
      more than 99% of the fucose, galactose, GalNAc and GlcNAc in CM. Total mucin
      outputs in ileal digesta, 5.32 and 5.65 g/day from SAI and AAI Pigs (p = 0.24),
      respectively, were determined from the total GalNAc output in digesta, assuming
      soluble and insoluble mucin had similar compositions. Based on these outputs,
      mucin represented approximately 30, 7 to 22, 15 and 11% of the endogenous
      threonine, proline, serine and protein, respectively, in ileal digesta.
      Approximately 74, 76, 100 and 53% of the fucose, galactose GalNAc and GlcNAc,
      respectively, in ileal digesta from pigs in this study was attributed to mucin.
      The results from this study demonstrate the importance of mucin as a source of
      some endogenous amino acids and carbohydrates.

PMID- 9246735
TI  - Intra-oral lactic acid production during clearance of different foods containing
      various carbohydrates.
AB  - Oral carbohydrate clearance and acid production were monitored over a two hour
      time period following the ingestion of six foods (chocolate bar, potato chip,
      oreo cookie, sugar cube, raisin and jelly bean). Each food was evaluated intra
      orally in eight volunteers. Oral fluid samples were obtained from each volunteer
      at 30 min intervals at five different tooth sites using absorbent paper points.
      The oral fluid samples were analyzed qualitatively and quantitatively for
      carbohydrates and organic acids using high performance liquid chromatography.
      Data obtained for each food were averaged and subjected to statistical analysis.
      The quantity of lactic acid produced 30 min after ingestion was found to be in
      the following order: (highest) raisin > chocolate bar > sugar cube > jelly bean >
      oreo cookie > potato chip (least). Two hours after food intake the order had
      changed significantly: potato chip > jelly bean > sugar cube > chocolate bar >
      oreo cookie > raisin. A direct linear relationship existed between lactic acid
      production and the presence of glucose. In foods containing cooked starch
      prolonged clearance occurs via the intermediate metabolites maltotriose, maltose
      and glucose. Results indicated that the term 'stickiness', when used to label
      certain foods such as jelly bean and chocolate bar, should be used cautiously.
      Foods containing only cooked starch or cooked starch and sugars can be considered
      as 'sticky', since glucose arising from their intra-oral degradation contributed
      to acid production over prolonged periods of time.

PMID- 9246736
TI  - Acute subdural hematoma associated with nontraumatic aneurysm rupture.
AB  - Five cases of subdural hematoma due to aneurysm rupture and their surgical
      treatment are reviewed. One patient recovered completely, one was severely
      disabled and 3 patients died. The literature regarding subdural hematomas
      associated with nontraumatic aneurysm rupture is reviewed and our therapeutical
      strategy is discussed. We conclude that severe neurological deficit and uncal
      herniation can be reversible if surgery is performed early.

PMID- 9246737
TI  - Guidelines for treatment of head injury in adults. Opinions of a group of
      neurosurgeons.
AB  - There are a number of parallel activities world wide to devise guidelines for the
      treatment of head injuries. A Group of neurosurgeons from various European
      countries worked on guidelines during three informal meetings, which may serve as
      a base for discussion of national or local protocols. Three levels of certainty
      were distinguished: Measures that must be taken which such a high degree of
      certainty, that they have not seriously been challenged-principles. Measures,
      that should be taken, as there is reasonable evidence in the literature about its
      efficacy-recommendations and measures that may be taken, but proof of its
      efficacy is lacking-optional measures. Protocols based on these guidelines are
      felt to help young neurosurgeons in training, define neurosurgical needs for
      other specialities and enhance the general efficacy of care for the head injured
      patient including multiple injuries.

PMID- 9246738
TI  - Microbiology and biodegradation of resin acids in pulp mill effluents: a
      minireview.
AB  - Resin acids, a group of diterpenoid carboxylic acids present mainly in softwood
      species, are present in many pulp mill effluents and toxic to fish in recipient
      waters. They are considered to be readily biodegradable. However, their removal
      across biological treatment systems has been shown to vary. Recent studies
      indicate that natural resin acids and transformation products may accumulate in
      sediments and pose acute and chronic toxicity to fish. Several resin acid
      biotransformation compounds have also been shown to bioaccumulate and to be more
      resistant to biodegradation than the original material. Until recently, the
      microbiology of resin-acid degradation has received only scant attention.
      Although wood-inhabiting fungi have been shown to decrease the level of resin
      present in wood, there is no conclusive evidence that fungi can completely
      degrade these compounds. In contrast, a number of bacterial isolates have
      recently been described which are able to utilize dehydroabietic or isopimaric
      acids as their sole carbon source. There appears to be an unusually high degree
      of substrate specificity with respect of the utilization of abietane congeners
      and the presence of substituents. Pimaranes do not appear to be attacked to the
      same extent as the abietanes. This paper reviews the occurrence, chemistry,
      toxicity, and biodegradation of resin acids in relation to the biological
      treatment of pulp and paper mill effluents.

PMID- 9246739
TI  - Molecular analysis of lytic genes of bacteriophage 80 alpha of Staphylococcus
      aureus.
AB  - Nucleotide sequencing of a 3779-bp fragment of the Staphylococcus aureus
      bacteriophage 80 alpha revealed two open reading frames: ORF1, designated as
      lytA, which encodes a polypeptide of 481 amino acids with an apparent M(r) of
      53.81 kDa; and ORF2, designated as holin, which encodes for a hydrophobic
      polypeptide of 145 amino acids with an apparent M(r) of 15.58 kDa and exhibits
      two putative transmembrane helices. Both genes showed 100% sequence homology to
      that of the peptidoglycan hydrolase and holin genes of the S. aureus phage phi 11
      reported earlier. In addition, the downstream sequences of the lytA gene were
      homologous to the phage attachment site (attP) of the phage phi 11. Based on our
      data we propose that the lytic system of the phage 80 alpha evolved from that of
      phage phi 11.

PMID- 9246740
TI  - Characteristics of a nitropropanol-metabolizing bacterium isolated from the
      rumen.
AB  - We report some characteristics of a ruminal bacterium (strain NPOH1) that
      metabolizes 3-nitropropanol, the toxic principle of various milk vetchs that are
      distributed worldwide. The gram-positive bacterium was nonmotile and did not
      produce spores. Growth of strain NPOH1 occurred under anaerobic conditions and
      was supported by the electron acceptors 3-nitropropanol, 3-nitropropionate,
      nitrate, 2-nitropropanol, nitroethane, nitroethanol, or 3-nitro-1-propyl-beta-D
      glucopyranoside (miserotoxin). Other potential electron acceptors, namely
      sulfate, sulfite, azide, chlorate, perchlorate, nitrite, fumarate, 2-nitrobutane,
      or nitrobenzene, did not support growth. Formate, lactate, and H2 stimulated
      growth of strain NPOH1 in the presence of the appropriate nitrocompound, whereas
      a variety of other potential H2 donors did not. When grown in medium containing
      both nitrate and either 3-nitropropanol or 3-nitropropionate, nitrate was the
      preferred acceptor. Strain NPOH1 reduced nitrate to nitrite and, when grown with
      excess reductant, nitrite was further reduced to ammonia. The products formed
      during the metabolism of 3-nitropropanol and 3-nitropropionate by mixed ruminal
      populations, 3-aminopropanol and beta-alanine, were not found in culture fluids
      of strain NPOH1. Analysis of total cellular fatty acid profiles and of the mole
      percent guanine plus cytosine suggests that strain NPOH1 is a novel bacterium.
      The capacity of strain NPOH1 to metabolize 3-nitropropanol suggests that this
      organism may play an important role in detoxification of 3-nitropropanol in the
      rumen.

PMID- 9246742
TI  - Murine macrophage elastolytic activity induced by Aspergillus fumigatusstrains in
      vitro: evidence of the expression of two macrophage-induced protease genes.
AB  - The interaction between Aspergillus fumigatus conidia and murine macrophages of
      various origins was investigated. Cocultures were carried out between A.
      fumigatus strains and freshly isolated murine pulmonary alveolar macrophages or
      two murine macrophage cell-lines: murine alveolar cell-line MALU and murine
      astrocytoma cell-line J774. By measuring the variation of elastolytic activity in
      the coculture supernatants with two elastin substrates, we demonstrated that
      either viable or fixed A. fumigatus or C. albicans yeasts or nonspecific
      particles induced significant macrophage elastolytic activity. The effect of A.
      fumigatus supernatant or the purified A. fumigatus galactomannan suggested also
      the possible involvement of this polysaccharide in macrophage-protease gene
      expression, release, and activity in invasive aspergillosis. The effect of
      inhibitory compounds demonstrated the potential implication of a macrophagic
      metalloprotease and a macrophagic cysteine protease. RNA analysis allowed us to
      demonstrate the induction of expression of two macrophagic protease genes in
      stimulated macrophages. Two distinctive mechanisms appeared to be implicated in
      macrophage protease induction: nonspecific phagocytosis in the earliest times of
      the coculture and (or) specific galactomannan recognition after its gradual
      release by the mycelium.

PMID- 9246743
TI  - A rapid viability assay for Cryptosporidium oocysts and Giardia cysts for use in
      conjunction with indirect fluorescent antibody detection.
AB  - There is an urgent need to develop rapid methods to determine the viability of
      Cryptosporidium oocysts and Giardia cysts in environmental samples, especially
      water. The inclusion of the vital dye propidium iodide (PI) by oocysts and cysts
      has been previously shown to correlate well with nonviability. The ability of
      nonviable oocysts and cysts to include PI has been employed to develop a rapid
      viability determination method that could be used in conjunction with the current
      indirect fluorescent antibody (IFA) method for detecting oocysts and cysts. The
      efficacy of this PI-IFA method to detect and determine the viability status of
      oocysts/cysts has been tested using oocyst samples inactivated by three different
      approaches. The ability to incorporate PI staining with IFA detection provides
      the advantage of both detection and viability determination at the same time,
      using the same sample.

PMID- 9246744
TI  - Molecular characterization of coat protein genes of serologically distinct
      isolates of potato virus Y necrotic strain.
AB  - The cost protein (CP) genes of two potato virus Y necrotic isolates (N27 and a
      mutant strain N27-92), which differed in their reactivity to a monoclonal
      antibody (mab), were characterized. Both isolates could be detected by mab 4E7,
      but mab VN295.5 selectively reacted to N27 and not to N27-92. The CP genes of
      both isolates coded for 267 amino acids with approximately 99.0% identity at both
      the nucleotide and the amino acid levels. nucleotide sequence comparison
      indicated five substitutions in N27-92 compared with N27. Three of these changes
      resulted in substitution of amino acids. Two transitions (A-->G) in N27-92
      changed threonine to alanine and lysine to arginine at positions 7 and 55,
      respectively, whereas a A-->T transversion changed asparagine to isoleucine at
      positions 27. The surface probability curves of both the isolates could almost be
      superimposed, except at amino acid positions 7 and 27. Since amino acid
      substitution at position 55 is conservative, changes from polar to hydrophobic
      amino acids (threonine-->alanine and asparagine-->isoleucine) at positions 7 and
      27 might have changed the epitope(s) of N27-92, abolishing its detection by mab
      VN295.5.

PMID- 9246745
TI  - Tributyltin oxide affects energy production in the yeast Rhodotorula ferulica, a
      utilizer of phenolic compounds.
AB  - Rhodotorula ferulica, a yeast able to utilize phenolic compounds, was chosen for
      evaluating the effects of tributyltin oxide (TBTO) on this utilization. TBTO
      reduced respiratory capacity when vanillic or benzoic acid was the energy source.
      The ATP level of the cells was severely affected by 2 microM TBTO. The
      mitochondrial ATPase was strongly inhibited by 0.5 microM TBTO, whereas the
      activity of the plasma membrane ATPase was not affected by concentrations of TBTO
      up to 30 microM. Our data support the hypothesis that the target for TBTO action
      is the mitochondrial ATPase, resulting in a severe disturbance of the yeast
      utilization of aromatic compounds.

PMID- 9246746
TI  - Sources of variation in isolation rate of Giardia lamblia cysts and their
      homogeneous distribution in river water entering a water treatment plant.
AB  - The objective of this work was to determine if differences in the number of
      Giardia cysts measured in river water were due to the method itself, the analyst,
      or real differences in the distribution of these cysts in water. To minimize the
      methodological differences, centrifugation only was used as the primary
      concentration method. Differences were observed between results from different
      analysts and they were identified as technical errors. Once the method had been
      well established, cysts were found to be distributed homogeneously in the river
      water tested. Small differences were observed among samples collected
      sequentially at the same time, as well as for samples collected on different days
      or at different times on the same day. The differences reported in the literature
      in the number of Giardia cysts detected in water samples from the same site could
      be an artifact of the methods more than true differences in the counts.

PMID- 9246747
TI  - Antirheumatic agents. III. Novel methotrexate derivatives bearing an indoline
      ring and a modified ornithine or glutamic acid.
AB  - The synthesis, biological profile and structure-activity relationship of various
      methotrexate (MTX) derivatives bearing an indoline ring are described. In
      particular, Nb-(3-carboxyphenyl)-N alpha-[1-[(2,4-diaminopteridin-6-yl)-methyl]
      indoline-5-ylcarbonyl]-L-glutamine (3d), compared to MTX, exhibited an enhanced
      anti-proliferative effect on human peripheral blood mononuclear cells obtained
      from healthy volunteers.

PMID- 9246748
TI  - Pyridazines. XIII. Synthesis of 6-aryl-5-oxygenated substituted-3(2H)
      pyridazinones and evaluation as platelet aggregation inhibitors.
AB  - Several 6-aryl-5-oxygenated substituted pyridazinones have been synthesized and
      evaluated in vitro for inhibition of platelet aggregation induced by adenosine 5'
      diphosphate (ADP), thrombin and collagen. All the tested compounds (except 8 and
      9) inhibited platelet aggregation in a dose-dependent manner. The IC50 of the
      most active substance, compound 2b, was around 60 microM against ADP and collagen
      as inducers. The inhibition of platelet aggregation caused by test compounds was
      dependent on the level of oxidation of the function at the 5-position, with the
      order of IC50 values being R-OH (2a, b, 5) < R-CHO (6, 7) < < R-COOH (8, 9). None
      of the tested compounds increased the intracellular levels of cAMP, indicating a
      lack of inhibitory activity on cAMP phosphodiesterase (PDE III) in intact cells.
      These results suggest that the group present at the 5 position of 6-aryl-5
      substituted pyridazinones determines the platelet aggregation-inhibitory
      activity, and that a mechanism other than PDE inhibition is responsible for this
      effect.

PMID- 9246749
TI  - Synthesis and antitumor activity of 9-acyloxyellipticines.
AB  - Various kinds of water-soluble 9-acyloxyellipticine derivatives were synthesized
      in a search for compounds with potent antitumor activity. Antitumor activities
      against several tumors in mice (P388 leukemia, colon 26, Lewis lung carcinoma and
      B16 melanoma) were evaluated by using intravenous administration. Many compounds
      exhibited good antitumor activities; in particular, the glutarate derivative (5o)
      showed potent antitumor activity. This compound (5o) may be converted to 9
      hydroxyellipticine (2) by enzyme-catalyzed hydrolysis in the body.

PMID- 9246750
TI  - New neplanocin analogues. VIII. Synthesis and biological activity of 6'-C-ethyl, 
      ethenyl, and -ethynyl derivatives of neplanocin A.
AB  - This report describes the synthesis and antiviral effects of (6'R)-6'-C-ethynyl, 
      ethenyl, and -ethyl derivatives of neplanocin A (7a, 8a, and 9a, respectively)
      and the corresponding 6'S-diastereomers (7b, 8b, and 9b, respectively), as
      examples of 6'-C-substituted analogues of neplanocin A. Grignard reaction of the
      6'-formyl derivative 4, which was readily prepared from neplanocin A, with
      ethynylmagnesium bromide gave a diastereomeric mixture of the corresponding 1,2
      addition products 5a and 5b. After removal of the protecting groups, (6'R)- and
      (6'S)-6'-C-ethynylneplanocin A's (7a, 7b) were separated. The corresponding
      ethenyl derivatives 8a and 8b and ethyl derivatives 9a and 9b were prepared by
      catalytic hydrogenation of 7a and 7b, respectively. As compared to neplanocin A,
      the new neplanocin A derivatives were much weaker inhibitors of S-adenosyl-L
      homocysteine hydrolase, the R-diastereomers being more inhibitory than the S
      diastereomers. The decreasing order of activity was 7a > 8a > 7b > 9a > 8b > 9b.
      The cytotoxicity (for CEM cells) followed exactly the same order. Of these
      compounds, (6'R)-6'-C-ethynylneplanocin A (7a, RENPA) showed an antiviral
      activity spectrum that was comparable to, and an antiviral specificity that was
      higher than, that of neplanocin A. RENPA was particularly active against those
      viruses (i.e. vaccinia virus, vesicular stomatitis virus) that are known to be
      highly sensitive to AdoHcy hydrolase inhibitors.

PMID- 9246751
TI  - Synthesis and antifungal activity of novel thiazole-containing triazole
      antifungals.
AB  - A new series of thiazole-containing triazole antifungals was synthesized and
      evaluated for antifungal activity against a variety of clinically isolated
      pathogenic fungi in vitro and against systemic candidosis in vivo. Among these
      compounds, (+/-)-1-(2,4-difluorophenyl)-1-[4-(2,4-difluorophenyl) thiazol-2-yl]-2
      (1H-1,2,4-triazol-1-yl)ethanol (ER24161) showed the most potent and well-balanced
      in vitro activities and excellent in vivo efficacy. We also achieved an
      enantioselective synthesis of the more potent enantiomer of ER-24161.

PMID- 9246752
TI  - Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors.
      III. Synthesis and gastric antisecretory activity of 2-[(2- and 4-aminobenzyl,
      and alpha-methylbenzyl)sulfinyl]-N-(4-pyridinyl) -3-pyridinecarboxamides.
AB  - A new series of 2-[(2-aminobenzyl, 4-aminobenzyl, and alpha-methylbenzyl)
      sulfinyl]-N-(4-pyridinyl)-3-pyridinecarboxamides. was synthesized and evaluated
      for gastric antisecretory activities. Several of the compounds synthesized
      exhibited potent inhibitory activities against [14C]aminopyrine accumulation
      stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and
      histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal
      administration. In particular, the more polar diastereoisomer of 2-[(4-methoxy
      alpha-methylbenzyl)sulfinyl] -N-(4-pyridinyl)-3-pyridinecarboxamide (13b) showed
      in vivo inhibitory activity equivalent or superior to that of omeprazole and was
      a more selective (H+/K+)-ATPase inhibitor than omeprazole.

PMID- 9246753
TI  - Bioactive saponins and glycosides. X. On the constituents of zizyphi spinosi
      semen, the seeds of Zizyphus jujuba Mill. var. spinosa Hu (1): structures and
      histamine release-inhibitory effect of jujubosides A1 and C and acetyljujuboside
      B.
AB  - New dammarane-type triterpene oligoglycosides, jujubosides A1 and C and
      acetyljujuboside B1 were isolated from Zizyphi Spinosi Semen, the seeds of
      Zizyphus jujuba MILL. var. spinosa Hu, together-with three known saponins. The
      structures of jujubosides A1 and C and acetyljujuboside B were determined on the
      basis of chemical and physicochemical evidence. Jujubosides A1 and C and
      acetyljujuboside B were found to inhibit the histamine release from rat
      peritoneal exudate cells induced by antigen-antibody-reaction.

PMID- 9246754
TI  - N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline, a potent muscarinic
      agonist.
AB  - The muscarine receptor agonist SK-946, an aniline derivative with a
      characteristic bicyclo amine, was found. We describe a new synthetic method for 1
      azabicyclo[3.3.0]octane and describe the biological activity of SK-946.

PMID- 9246755
TI  - The 1995 list. Proposed new bacterial taxa and proposed changes of bacterial
      names published during 1995 and considered to be of interest to medical or
      veterinary bacteriology (an informational note).

PMID- 9246756
TI  - The Escherichia coli cell cycle, cell division and ppGpp: regulation and
      mechanisms.
AB  - The literature demonstrating tight regulation of the Escherichia coli cell cycle
      is reviewed. Recent evidence is presented indicating that the normal rod cell
      shape can be abandoned, allowing growth as a coccus, either by increasing the
      amount of the division proteins FtsZ, FtsA and FtsQ, or by increasing the pool of
      the nucleotide ppGpp. It is argued that ppGpp may be a cell cycle signal in E.
      coli.

PMID- 9246757
TI  - Diversity and specificity of protein-phosphorylating systems in bacteria.
AB  - Bacteria harbor three different protein-phosphorylating systems which regulate
      distinct physiological processes: first, the nucleotide-dependent system which
      modifies hydroxyl groups of amino acids in protein substrates; second, the two
      component system which involves both sensor kinase and response regulator; third,
      the phosphoenolpyruvate-dependent phosphotransferase system. These systems share
      a number of structural and functional similarities with the protein
      phosphorylating systems of eukaryotes.

PMID- 9246758
TI  - Regulation of carbon metabolism in gram-positive bacteria by protein
      phosphorylation.
AB  - The main function of the bacterial phosphotransferase system is to transport and
      to phosphorylate mono- and disaccharides as well as sugar alcohols. However, the
      phosphotransferase system is also involved in regulation of carbon metabolism. In
      Gram-positive bacteria, it is implicated in carbon catabolite repression and
      regulation of expression of catabolic genes by controlling either catabolic
      enzyme activities, transcriptional activators or antiterminators. All these
      different regulations follow a protein phosphorylation mechanism.

PMID- 9246759
TI  - Protein secretion by gram-negative bacterial ABC exporters.
AB  - One of the strategies used by Gram-negative bacteria to secrete proteins across
      the two membranes which delimit the cells, is sec independent and dedicated to
      proteins lacking an N-terminal signal peptide. It depends on ABC protein-mediated
      exporters, which consist of three cell envelope proteins: two inner membrane
      proteins: an ATPase (the ABC protein), a membrane fusion protein (MFP) and an
      outer membrane polypeptide. Erwinia chrysanthemi metalloproteinases B and C, and
      Serratia marcescens hemoprotein HasA are secreted by such homologous pathways and
      interact with the ABC protein. Interaction between the ABC protein and its
      substrate has also been evidenced by studies on proteinase and HasA hybrid
      transporters obtained by combining components from each system. Association
      between hemoprotein HasA and the three exporter/secretion proteins was
      demonstrated by affinity chromatography on hemin agarose on which the substrate
      remained bound with the three secretion proteins. The three component association
      was ordered and substrate binding was required for the formation of this
      multiprotein complex.

PMID- 9246761
TI  - Biological activity of new aza analogues of quinolones.
AB  - A series of novel derivatives of 4H-pyrido[1,2-]pyrimidine, 1,4-dihydro-4-oxo-1,5
      naphthyridine and 1,4-dihydro-4-oxo-1,6-naphthyridine were prepared and their
      biological activity was compared with that of nalidixic acid. The in vitro
      antibacterial activity of the tested compounds was lower than that of nalidixic
      acid except for two agents, 1b and 2c, with a higher activity against
      Enterococcus faecalis. The compounds were tested for their ability to cure four
      plasmids from two species of Enterobacteriaceae. The derivatives eliminated three
      plasmids (pKM101, pBR322, F'lac) at one-half or one-quarter of the minimal
      inhibitory concentration. Plasmid RP4 was unaffected by the treatment. None of
      these compounds showed better antichloroplast activity than nalidixic acid.

PMID- 9246760
TI  - Pullulanase: model protein substrate for the general secretory pathway of gram
      negative bacteria.
AB  - Pullulanase of Klebsiella oxytoca is one of a wide variety of extracellular
      proteins that are secreted by Gram-negative bacteria by the complex main terminal
      branch (MTB) of the general secretory pathway. The roles of some of the 14
      components of the MTB are now becoming clear. In this review it is proposed that
      most of these proteins form a complex, the secretion, that spans the cell
      envelope to control the opening and closing of channel in the outer membrane.
      Progress toward the goal of testing this model is reviewed.

PMID- 9246762
TI  - Survey of the microbiological quality of nonalcoholic carbonated beverages.
AB  - The number and the main groups of microorganisms present in samples of different
      nonalcoholic carbonated beverages (lemon, orange and guarana soft drinks)
      obtained from small factory were analyzed. The samples were obtained at the end
      of the processing line. They were then divided into two lots: one was sent to
      immediate analysis, the other was stored at environmental temperature for 90 d
      thereafter it was submitted to the same analysis. Aliquots of 1 mL were drawn
      from the various samples and the corresponding decimal dilutions were prepared.
      They were then grown in culture media and counts of mesophilic aerobic bacteria,
      molds and yeasts, acid-producing bacteria, total and fecal coliforms were taken.
      It was observed that, of all the analyzed samples, at time 0 or storage sample C
      (orange) was the best, since it conformed to the microbiological standards
      established by legislation. The guarana type could also be consumed on day zero;
      the lemon type was inadequate for consumption of all the analyzed samples, the
      orange type was the only one that could be consumed within 3 months of storage.

PMID- 9246763
TI  - Fed-batch cultivation of bakers' yeast: effect of nutrient depletion and heat
      stress on cell composition.
AB  - The physiology of a commercial strain of bakers' yeast was studied in terms of
      the cell composition under different growth conditions and of its response to
      stress. The study comprised fed-batch experiments since this is the system used
      in bakers' yeast industry. The classical fed-batch fermentation procedure was
      modified in that the yeast cells were continuously grown to a steady-state at a
      dilution rate of 0.1/h in order to achieve more or less the same initial starting
      point in terms of cell composition. This steady-state culture was then switched
      to fed-batch concomitantly with exposure to stress. The highest amount of
      trehalose accumulation was achieved when nutrient depletion and heat stress were
      applied concomitantly. The highest amount of trehalose, 12%, was attained in
      cells stressed by both nitrogen depletion and heat stress. The protein content
      remained constant, although with some oscillations, at a value of 30% throughout
      this dual stress experiment.

PMID- 9246765
TI  - Morphology of rat kidney and thymus after native and antibody-coupled cyclosporin
      A application (reduced toxicity of targeted drug).
AB  - This study compares the toxic effects of native cyclosporia A (CyA) with those of
      targeted CyA that is conjugated with the anti-rat-thymocyte antibody of rabbit
      origin via the N-(2-hydroxypropyl)methacrylamide (HPMA) carrier bearing
      digestible, reactive oligopeptide side chains. Ten toxic doses of native CyA (50
      mg/kg i.p.) given to young adult rats in the course of 14 d produced a severe
      renal lesion-diffuse microvacuolization of the proximal tubules in the deep
      cortex, and hypergranulation of juxtaglomerular regions. Severe atrophy of the
      thymic medulla was documented by morphometry. In the cortex the epithelial
      reticular (but not deep interdigitating) cells showed ultrastructural signs of
      severe degeneration and lysis. The immature CD4+8+ double-positive cortical
      lymphocytes were preserved whereas the single-positive medullary thymocytes were
      greatly depleted; there was also a restriction of MHC class II antigen expression
      in the medulla. The number of medullary B cells was increased. The cytokeratin
      net was focally shrunken in the cortex and almost negative in the medulla, with
      loss of Hassall's corpuscles. After ten corresponding doses of antibody-targeted
      conjugated CyA no damage to the renal tubules and arterioles appeared and the
      antiGBM or immune-complex deposition was absent. The thymus had a normal medulla
      with numerous mature thymocytes and the cortical epithelial reticulum remained
      well preserved. Thus, the main toxic effects of CyA could be eliminated by
      targeting. The T-cell-targeted drug was tested for preserved immunosuppressive
      properties and non-toxic character of HPMA copolymer carrier.

PMID- 9246766
TI  - Cross-contamination and infection in the domestic environment and the role of
      chemical disinfectants.

PMID- 9246767
TI  - Analysis of conductance responses during depolymerization of pectate by soft rot
      Erwinia spp. and other pectolytic bacteria isolated from potato tubers.
AB  - Different bacteria isolated from potato tubers were screened for their pectolytic
      properties by examining pitting in polypectate agar, recording conductance
      responses in polypectate medium and performing potato tuber soft rot tests. For
      bacteria found positive in conductimetry, the role of polygalacturonase (PG) and
      pectate lyase (PL) in the generation of conductance changes in a polygalacturonic
      acid (PGA) medium was further analysed using enzyme activity staining after gel
      electrophoresis and high-performance anion exchange chromatography. The extent of
      the conductance changes during depolymerization of PGA was dependent on the
      amounts of galacturonate monomers and oligomers accumulated in the medium. In
      comparison with an unidentified saprophyte and a Klebsiella strain, both mainly
      having PL activity, soft rot Erwinia spp. rapidly produced larger conductance
      responses, due to a combined action of multiple forms of PG and PL. The responses
      of Erwinia spp. were initially associated with the accumulation of large amounts
      of monomers and saturated dimers to heptamers, due to PG activity. Subsequently,
      as well as monomers and saturated dimers, large amounts of unsaturated dimers
      were also detected, due to PL activity. The role of PG as an important
      conductimetric factor was also demonstrated for a pectinase preparation derived
      from Aspergillus niger. Besides detection, automated conductimetric assays in
      pectate media may also be useful for monitoring of pectolytic activity in
      pectinase preparations and for screening of pectolytic activity of microorganisms
      under different media and growth conditions.

PMID- 9246768
TI  - Physiological and biochemical studies on psychrotolerance in Listeria
      monocytogenes.
AB  - Studies were undertaken to explain the ability of Listeria monocytogenes to grow
      at low temperatures in a chemostat. It was found that when grown in continuous
      culture at a dilution rate of 0.02 h-1 L. monocytogenes had a lower proportion of
      anteiso-17:0, and a higher proportion of anteiso-15:0, and smaller chain fatty
      acids when grown at 10 degrees C compared to 30 degrees C. A previously
      unreported glycolipid was only seen after growth at low temperature. Growth
      temperature had no effect on the rate of glucose uptake.

PMID- 9246769
TI  - Effects of physico-chemical factors influencing tyramine production by
      Carnobacterium divergens.
AB  - Tyramine production by a strain of Carnobacterium divergens was tested in
      relation to different conditions of pH, temperature, glucose, oxygen
      availability, potassium nitrate and sodium chloride content, using a combination
      of a Doehlert and Plackett-Burman experimental design. A second degree polynomial
      model was chosen to describe tyramine production which was quantified by high
      performance liquid chromatography. Maximal tyramine production occurred during
      the stationary phase in acidic conditions obtained by low initial pH (< 5) or
      addition of glucose (0.6%) to the medium. Production was slower at 5 degrees C
      than at 23 degrees C and 10% sodium chloride inhibited this production. However,
      the formation of tyramine was not affected by the presence of potassium nitrate
      or oxygen availability.

PMID- 9246770
TI  - Microbiological composition of raw milk from selected farms in the Camembert
      region of Normandy.
AB  - Raw milk from 27 farms was sampled over 6 months for listerias, salmonellas,
      Yersinia enterocolitica and campylobacters. Total bacterial counts and somatic
      cell counts were measured. Lactococci, lactobacilli, dextran-producing
      leuconostocs, Brevibacterium linens, yeasts and moulds, Staphylococcus aureus and
      other Micrococcaceae, Pseudomonas, coliforms, Escherichia coli, enterococci,
      Clostridium perfringens and spores of anaerobic lactate-fermenting bacteria were
      also counted. Pseudomonas (2000 cfu ml-1), lactococci (760 cfu ml-1) and
      Micrococcaceae (720 cfu ml-1) were the most numerous groups. Lactic acid bacteria
      were detected in all samples. Coliforms were present in most samples, but 84% of
      samples had counts < 100 cfu ml-1. Staphylococcus aureus was detected in 62% of
      milks, the average count was 410 cfu ml-1. About 80% of supplies had < or = 10 E.
      coli cfu ml-1 and all samples had < or = 1 Cl. perfringens cfu ml-1. Two of the
      tested milks were positive for salmonellas (2.9%), four were positive for
      Listeria monocytogenes (5.8%), 25 for Yersinia enterocolitica (36%) and one for
      campylobacters (1.4%).

PMID- 9246771
TI  - CMC-liquefying enzyme, a low molecular mass initial cellulose-decomposing
      cellulase responsible for fragmentation from Streptomyces sp. LX.
AB  - LX, newly isolated from soil, was shown to secrete a carboxylmethylcellulose
      (CMC)-liquefying enzyme that cleaves the CMC chains, releasing negligible
      reducing terminals. The new enzyme, named component C2, was purified to
      homogeneity by dialysation. It has a molecular mass of 9.8 kDa. The pH optimum of
      the enzyme activity is 6.4 and its temperature optimum is 50 degrees C. It
      retains full activity at pH 4-6.4 upon incubation at 50 degrees C for 30 min. The
      enzyme has significant fragmentation activity on filter paper despite the absence
      of weight loss, release of reducing sugars and depolymerization during incubation
      with filter paper. The one-electron oxidative reaction is shown not to
      participate in the fragmentation of filter paper by enzyme C2.

PMID- 9246772
TI  - Influence of medium composition on the growth and antigen expression of
      Helicobacter pylori.
AB  - An evaluation of the ability of various solid and liquid media to support both
      growth and antigen expression, particularly lipopolysaccharide (LPS) expression,
      by Helicobacter pylori culture collection strains and clinical isolates was
      performed. Liquid-based basal media (brain heart infusion, Brucella broth,
      Mueller-Hinton broth and tryptone soya broth) supported the growth of strains,
      whereas solid basal media of the same formulation did not support growth. Optimal
      growth of all strains was obtained on solid and in liquid media containing blood.
      Supplemented solid media containing supplements other than blood supported growth
      but only to a small extent. In liquid media excluding blood, serum supplements
      enhanced growth and horse serum was found to be superior to fetal calf serum. In
      general, beta-cyclodextrin did not increase growth. Mueller-Hinton broth or
      tryptone soya broth containing horse serum and a nitrogen source such as yeast
      extract or proteose peptone no. 3 were found to give optimal growth of H. pylori
      in a blood-free environment. Strains after cultivation in liquid media,
      irrespective of composition, maintained production of high-molecular weight (mol.
      wt) LPS with an O side chain independent of medium composition, whereas
      subculturing on solid media resulted in production of low-mol. wt LPS. Expression
      of proteins differed in liquid and on solid media, particularly proteins of 57
      and 60 kDa, but qualitatively no differences were observed upon supplementation
      of basal media.

PMID- 9246773
TI  - The effects of agar concentration on the growth and morphology of submerged
      colonies of motile and non-motile bacteria.
AB  - The growth and morphology of submerged bacterial colonies was investigated. Five
      separate colonial forms were recognized depending both on species and on agar
      concentration. These were (i) branched, dendritic structures seen only with
      Bacillus cereus; (ii) lenticular colonies for all other species at high agar
      concentrations; (iii) small lobed to spherical colonies for non-motile organisms
      at low agar concentrations; (iv) and (v) large diffuse spherical colonies which
      can be further subdivided into 'snowball' or 'wispy' types for motile bacteria
      growing at agar concentrations below about 0.65% w/v. Viable count determinations
      suggested that agar concentration had little effect in the early stages of growth
      but that motile cells at low agar concentrations achieved higher cell numbers
      than did those in concentrations greater than 0.65% w/v. Transmission electron
      microscopy indicated that bacteria in lenticular colonies were tightly packed
      within lens-shaped splits in the agar whilst at low agar concentrations motile
      cells were well separated and appeared to move through the agar matrix.

PMID- 9246774
TI  - An improved plaque assay for poor plaque-producing temperate lactococcal
      bacteriophages.
AB  - This report summarizes the results from an effort to optimize the double-agar
      plate assay for visualization of the plaques made by six temperate bacteriophages
      induced from industrial strains of Lactococcus lactis. Among the several
      parameters found to influence the plaque assay, the effect of incorporating
      glycine into the growth medium was most striking, resulting in extensive increase
      in the plaque size of all of the 13 phage-host pairs tested. Notable effects on
      the plaque size of other factors such as the procedure for sterilization of the
      agar medium, the volume and softness of the top and bottom layers, and the number
      and growth stage of the bacterial cells added to the lawn, were also observed. By
      exploiting these findings in an optimized procedure for plaque assaying, several
      indicator strains were identified which were unable to support the development of
      plaques on standard double-agar plates. Since bacterial hosts usually are
      identified by their ability to support the development of plaques, this
      observation suggests that the severe difficulty experienced in identifying
      lactococcal starter strains that are sensitive towards a temperate phage, partly
      is a problem of methodology.

PMID- 9246775
TI  - Bacteriological stability and growth kinetics of Pseudomonas aeruginosa in
      bottled water.
AB  - Bacteriological stability of water bottled in plastic containers and the growth
      kinetics of Pseudomonas aeruginosa were determined. Samples of water from the
      source, water to be bottled, finished product and sterile water bottled in non
      returnable and returnable containers were analysed for aerobic colony count,
      coliforms, Escherichia coli and Ps. aeruginosa. The samples were examined for up
      to 30 d storage. Aerobic colony count increased 6 d after bottling to between
      10(3) and 10(5) cfu ml-1. Coliforms and E. coli were not found in any sample.
      Pseudomonas aeruginosa was isolated from commercial products bottled in
      returnable plastic containers due to the contamination from the containers and
      the subsequent multiplication utilizing trace nutrients. The predominant Ps.
      aeruginosa strains showed high doubling time (26 h) due to competition from the
      accompanying flora. In the absence of competing flora Ps. aeruginosa reached
      higher density than the maximum reached by aerobic flora, with a doubling time of
      only 3.6 h. After 30 d storage, this micro-organism was predominant.

PMID- 9246776
TI  - The effect of temperature, pH and medium in a surface adhesion immunofluorescent
      technique for detection of Listeria monocytogenes.
AB  - A rapid surface adhesion-based immunofluorescence technique was used to detect
      Listeria monocytogenes from inoculated culture systems. The effect of culture
      type (pure, mixed and meat), pH (7.00, 6.40, 4.76 and 3.13), acids (citric and
      HCl) and temperature (25 degrees, 30 degrees and 37 degrees C) on the adhesion of
      Listeria to the polycarbonate membrane used in this technique was determined. It
      was found that pH had a significant effect (P < 0.05) with higher numbers of
      Listeria adhering at low pH values (4.76). Culture type was also important with
      significantly higher numbers of Listeria (P < 0.05) adhering to membranes
      immersed in meat cultures than in pure or mixed cultures. This effect was seen at
      30 degrees C but not at 25 degrees or 37 degrees C. The total viable count (TVC)
      on the membrane was unaffected by pH but temperature had an influence with
      optimum adhesion occurring at 25 degrees C. The reasons for observed differences
      and their implications for the surface adhesion immunofluorescent rapid method
      are discussed.

PMID- 9246777
TI  - Antimicrobial activity of food-related Penicillium sp. against pathogenic
      bacteria in laboratory media and a cheese model system.
AB  - Food-related Penicillium species (n = 34) and Geotrichum candidum (n = 11) grown
      on Czapek Dox and brie agar were tested for their ability to suppress growth of
      pathogenic bacteria. Ten out of 13 P. camemberti showed antagonistic activity
      while the other species did not interact significantly with the bacterial growth.
      The order of inhibition was: Gram-negative bacteria and Bacillus cereus >
      Listeria monocytogenes, Lactococcus sp. > Micrococcus sp. whereas Lactobacillus
      sp., Staphylococcus aureus and some Micrococcus sp. were unaffected. When
      Salmonella typhimurium was inoculated together with P. camemberti P25 in brie
      agar, bacterial growth was inhibited during the first 6 d of incubation
      whereafter growth started. The inhibition of L. monocytogenes was similar but
      less pronounced. The antimicrobial activity produced by P. camemberti P25 and L84
      was enhanced with increasing amount of sucrose in the medium. The activity was
      increased at low pH and destroyed at pH above 8. It was detectable at 15 degrees
      C but not at 37 degrees C indicating that volatile metabolites might be involved.
      No significant accumulation of organic acids and no secondary metabolites such as
      mycotoxins were detected. HSGC-MS analysis indicated that acetaldehyde,
      benzaldehyde, 3-methylbutanal and 1-octen-3-ol were produced by P. camemberti
      during the period when inhibitory activity was observed. Pure acetaldehyde and
      benzaldehyde were shown to be inhibitory to L. monocytogenes and Salm.
      typhimurium when grown at 15 degrees C and pH 5.5 and 7.0.

PMID- 9246778
TI  - Enumeration of Enterococcus sp. using a modified mE method.
AB  - A modified mE medium (mEI) containing the chromogenic substrate indoxyl-beta-D
      glucoside to detect beta-D-glucosidase activity was evaluated with respect to
      specificity and recovery of enterococci from environmental waters. Extending
      incubation from 24 to 48 h improved enterococci recovery but 77% of the colonies
      classified as non-target were confirmed as enterococci. Randomly chosen
      enterococcal isolates from sewage, exposed in microcosms containing 0.22 micron
      membrane filtered fresh or estuarine water, exhibited differences in persistence
      as a function of exposure treatment. Decreasing the concentration of or
      eliminating indoxyl-beta-D-glucoside from mE did not significantly affect
      recovery of purified isolates.

PMID- 9246779
TI  - Pediocin PD-1, a bactericidal antimicrobial peptide from Pediococcus damnosus
      NCFB 1832.
AB  - Pediocin PD-1, produced by Pediococcus damnosus NCFB 1832, is inhibitory to
      several food spoilage bacteria and food-borne pathogens. However, pediocin PD-1
      is not active against other Pediococcus spp. and differs in this respect to other
      pediocins produced by Pediococcus acidilactici and Pediococcus pentosaceus.
      Production of pediocin PD-1 starts during early growth and reaches-a plateau at
      the end of exponential growth. Pediocin PD-1 was partially purified and its size
      was determined by tricine-SDS-PAGE as approximately 3.5 kDa. The isoelectric
      point (pI) of pediocin PD-1 is approximately 3.5, as determined with the Rotofor
      electrofocusing cell (BioRad). Pediocin PD-1 is heat-resistant (10 min at 121
      degrees C) and remains active after 30 min of incubation at pH 2-10. Pediocin PD
      1 is resistant to treatment with pepsin, papain, alpha-chemotrypsin and trypsin,
      but not Proteinase K. Pediocin PD-1 is bactericidal against sensitive cells of
      Oenococcus oeni (previously Leuconostoc oenos).

PMID- 9246780
TI  - Effects of anoxia, acidosis and temperature on the contractile properties of
      turtle cardiac muscle strips.
AB  - The responses to anoxia and acidosis of cardiac ventricular muscle strips from
      the anoxia-tolerant turtle Chrysemys picta bellii were investigated at 10 degrees
      C and 20 degrees C. Force-velocity curves were determined by quick isotonic
      releases at 85% of the time to peak isometric force under control, anoxia,
      lactate acidosis and anoxic lactate acidosis conditions. The isotonic forces
      during quick releases spanned 5-95% of the measured isometric force at each
      conditions. Superfusion solution pH was 7.8 and 7.95 for non-acidosis
      experiments, and 7.0 and 7.15 for acidosis experiments, at 20 degrees C and 10
      degrees C, respectively. After normalizing force data to control isometric force,
      the values of maximum isometric force (P0), maximum velocity of shortening (Vmax)
      and maximal power output (Powermax) were evaluated by fitting the curves using
      the hyperbolic Hill equation. The maximum rate of force development (dF/dtmax),
      time-to-peak force (TPF) and half-relaxation time (T1/2) were also determined. At
      20 degrees C, during acidosis, anoxia and anoxic acidosis, P0 decreased
      significantly to 81%, 40% and 24% of control values, dF/dtmax decreased
      significantly to 67%, 53% and 23% of control values, and Powermax decreased
      significantly to 75%, 40% and 14% of control values, respectively. Vmax, however,
      was not significantly affected by acidosis, anoxia or even anoxia acidosis. TPF
      was significantly shortened by anoxia, but prolonged by acidosis. The effects
      were similar at 10 degrees C, Temperature did not affect P0, but Vmax decreased
      by a factor of 1.6-1.8 at all corresponding conditions when temperature was
      reduced from 20 degrees C to 10 degrees C. We conclude that acidosis and anoxia
      inhibit isometric force production and Powermax of turtle cardiac muscle, but
      have no effect on Vmax, and the insensitivity of Vmax indicates that the rate of
      cross-bridge cycling is not affected by these conditions. Our observations
      indicate that the reduced power outputs of the hearts of submerged anoxic turtles
      at low temperature are due in part to inhibition of force production by anoxia
      and acidosis, and to a reduction of contraction velocity at low temperature.

PMID- 9246781
TI  - Heart rate and stroke volume contribution to cardiac output in swimming yellowfin
      tuna: response to exercise and temperature.
AB  - Cardiac performance in the yellowfin tuna (Thunnus albacares, 673-2470 g, 33-53
      cm fork length, FL) was examined in unanesthetized fish swimming in a large water
      tunnel. Yellowfin tuna were fitted with either electrocardiogram electrodes or a
      transcutaneous Doppler blood-flow probe over the ventral aorta and exposed to
      changes in swimming velocity (range 0.8-2.9 FLs-1) or to an acute change in
      temperature (18-28 degrees C). Heart rates (fH) at +/-1 degree C (30-130 beats
      min-1) were lower on average than previous measurements with non-swimming
      (restrained) tunas and comparable with those for other active teleosts at similar
      relative swimming velocities. Although highly variable among individuals, fH
      increased with velocity (U, in FLs-1) in all fish (fH = 17.93U + 49.93, r2 =
      0.14, P < 0.0001). Heart rate was rapidly and strongly affected by temperature
      (Q10 = 2.37). Blood flow measurements revealed a mean increase in relative
      cardiac output of 13.6 +/- 3.0% with exercise (mean velocities 1.23-2.10 FLs-1)
      caused by an 18.8 +/- 5.4% increase in fH and a 3.9 +/- 2.3% decrease in stroke
      volume. These results indicate that, unlike most other fishes, cardiac output in
      yellowfin tuna is regulated primarily through increases in fH. Acute reductions
      in ambient temperature at slow swimming velocities resulted in decreases in
      cardiac output (Q10 = 1.52) and fH (Q10 = 2.16), but increases in stroke volume
      (Q10 = 0.78). This observation suggests that the lack of an increase in stroke
      volume during exercise is not due to the tuna heart operating at maximal
      anatomical limits.

PMID- 9246782
TI  - Oxygen transport and cardiovascular responses to exercise in the yellowfin tuna
      Thunnus albacares.
AB  - Yellowfin tuna Thunnus albacares (1400-2175 g) instrumented with
      electrocardiogram electrodes and pre- and post-branchial catheters were subjected
      to incremental swimming velocity tests. Increasing velocity, from a minimal speed
      of 1.0 FLs-1, where FL is fork length, resulted in a 1.4-fold increase in heart
      rate (from 61.4 to 84.6 beats min-1), an elevated ventral-aortic blood pressure
      (from 10.8 to 12.2 kPa) and a decreased systemic vascular resistance. Relative
      branchial vascular resistance at minimal speed ranged from 24.4 to 40.0% of total
      vascular resistance and tended to increase with velocity. Yellowfin blood has a
      high oxygen-carrying capacity (16-18 ml O2 dl-1), and a low in vivo oxygen
      affinity (P50 = 5.3 kPa). Exercise caused a rise in arterial saturation (from 74
      to 88%) and a decline in venous saturation (from 48 to 44%), resulting in a 1.3
      fold increase in tissue oxygen extraction from the blood (arterial-venous oxygen
      content difference). Whereas arterial oxygen partial pressure (PO2) tended to
      increase with exercise, venous PO2 remained unchanged (approximately 5.3 kPa).
      The observed decrease in venous oxygen content was brought about by a lowered
      blood pH (from 7.80 to 7.76) and a large Bohr shift. Cardiac output and the
      increased blood oxygen extraction are estimated to have contributed nearly
      equally to the increased oxygen consumption during exercise. The large venous
      oxygen reserve still available to yellowfin tuna at maximal prolonged velocities
      suggests that the maximal oxygen delivery potential of the cardiovascular system
      in this species is not fully utilized during aerobic swimming. This reserve may
      serve other aerobic metabolic processes in addition to continuous swimming.

PMID- 9246783
TI  - Spatial acuity of ultrasound hearing in flying crickets.
AB  - The minimum audible angle is the smallest angular separation at which two sounds
      are perceived as coming from distinct sources. To determine the spatial acuity of
      hearing in crickets, we measured minimum audible angles at various locations in
      azimuth and elevation. Crickets (Teleogryllus oceanicus) were able to
      discriminate between sources separated by 11.25 degrees (1/32 of a circle) in
      azimuth directly ahead of them; acuity declined to 45 degrees in azimuth for
      sound sources 90 degrees to the side and then improved to 33.75 degrees at the
      rear. Crickets were also able to discriminate between sources separated in
      elevation, although acuity was much poorer, ranging from 45 degrees at the front
      and rear of the animal to 90 degrees below the animal. A habituation
      dishabituation test was used to test discrimination. This involved presenting a
      train of ultrasound pulses from one location, habituating the cricket's escape
      response. This train was followed by a test pulse of ultrasound from another
      location, after which a final pulse was presented from the original source. If
      the test pulse was discriminated from the habituating pulses, then the response
      to the final pulse was dishabituated. To determine the minimum audible angle, we
      repeated such tests while moving the two sound sources closer together until
      dishabituation no longer occurred.

PMID- 9246784
TI  - Tissue-specific variation in Hsp70 expression and thermal damage in Drosophila
      melanogaster larvae.
AB  - All tissues of larval Drosophila melanogaster express Hsp70, the major heat-shock
      protein of this species, after both mild (36 degrees C) and severe (38.5 degrees
      C) heat shock. We used Hsp70-specific immunofluorescence to compare the rate and
      intensity of Hsp70 expression in various tissues after these two heat-shock
      treatments, and to compare this with related differences in the intensity of
      Trypan Blue staining shown by the tissues. Trypan Blue is a marker of tissue
      damage. Hsp70 was rarely detectable before heat shock. Brain, salivary glands,
      imaginal disks and hindgut expressed Hsp70 within the first hour of heat shock,
      whereas gut tissues, fat body and Malpighian tubules did not express Hsp70 until
      4-21 h after heat shock. Differences in Hsp70 expression between tissues were
      more pronounced at the higher heat-shock temperature. Tissues that expressed
      Hsp70 slowly stained most intensely with Trypan Blue. Gut stained especially
      intensely, which suggests that its sensitivity to heat shock may limit larval
      thermotolerance. These patterns further suggest that some cells respond primarily
      to damage caused by heat shock rather than to elevated temperature per se and/or
      that Hsp70 expression is itself damaged by heat and requires time for recovery in
      some tissues.

PMID- 9246785
TI  - Excitation of identified serotonergic neurons by escape command neurons in
      lobsters.
AB  - Serotonin-containing neurosecretory neurons in the first abdominal ganglion (A1 5
      HT cells) of the lobster (Homarus americanus) ventral nerve cord have been shown
      previously to function as 'gain setters' in postural, slow muscle, command neuron
      circuitries. Here we show that these same amine neurons receive excitatory input
      from lateral (LG) and medial (MG) giant axons, which are major interneurons in
      phasic, fast muscle systems. Activation of either LG or MG axons elicits short
      latency, non-fatiguing, long-lasting excitatory postsynaptic potentials (EPSPs)
      in A1 5-HT cells which follow stimulus frequencies of up to 100 Hz in a 1:1
      fashion. Single spikes triggered in either giant axon can produce EPSPs in the A1
      5-HT cells of sufficient magnitude to cause the cells to spike and to fire
      additional action potentials after variable latencies; action potentials elicited
      in this way reset the endogenous spontaneous spiking rhythm of the A1 5-HT
      neurons. The giant-axon-evoked EPSP amplitudes show substantial variation from
      animal to animal. In individual preparations, the variation of EPSP size from
      stimulus to stimulus was small over the first 25 ms of the response, but
      increased considerably in the later, plateau phase of each response. When tested
      in the same preparation, EPSPs in A1 5-HT cells evoked by firing the LG axons
      were larger, longer-lasting and more variable than those triggered by firing the
      MGs. Firing A1 5-HT cells through an intracellular electrode, prior to activation
      of the giant fiber pathway, significantly reduced the size of LG-evoked EPSPs in
      A1 5-HT cells. Finally, morphological and physiological results suggest that
      similarities exist between giant fiber pathways in lobsters and crayfish. The
      possible functional significance of an involvement of these large amine
      containing neurosecretory neurons in both tonic and phasic muscle circuitries
      will be discussed.

PMID- 9246786
TI  - The olfactory memory of the honeybee Apis mellifera. III. Bilateral sensory input
      is necessary for induction and expression of olfactory blocking.
AB  - The associative learning phenomenon termed 'blocking' demonstrates that animals
      do not necessarily associate a conditioned stimulus (e.g. X) with reinforcement
      if X is coincident with a second conditioned stimulus (e.g. A) that had already
      been associated with the same reinforcement. Blocking therefore represents a
      tactic that animals can use to modulate associative learning in order to focus on
      the most predictive stimuli at the expense of novel ones. Using an olfactory
      blocking paradigm in the honeybee, we investigated the mechanistic basis for
      olfactory blocking. We show that removing input from one antenna eliminates the
      blocking of one odor by another. Since antennal sensory neurons only project to
      the ipsilateral antennal lobe in the honeybee, more central processing regions of
      the brain than the antennae must be crucial for establishing blocking. Further
      experiments show that this bilateral interaction between brain hemispheres is
      crucial during both the induction and the expression of blocking. This result
      implies that blocking involves an active inhibition of odor association and
      recall, and that this inhibition is mediated by a structure that spans both brain
      hemispheres. This interpretation is consistent with a role for identified
      bilateral modulatory neurons in the production of blocking.

PMID- 9246787
TI  - Trafficking of adoptively transferred B lymphocytes in B-lymphocyte-deficient
      mice.
AB  - Many studies have investigated the fate of adoptively transferred lymphocytes in
      recipient mice, although little is known of the sites where these transferred
      cells reside at particular time points. Using flow cytometry, we analyzed the
      trafficking pattern of adoptively transferred naive B cells into the lymphoid
      organs of syngeneic B-cell-deficient (microMT) mice. Within the first 24 h of
      transfer, the location of B cells was highly dependent on the mode of B-cell
      transfer. When B cells were injected subcutaneously into microMT mice, they
      showed a different trafficking pattern from cells administered into the
      peritoneal cavity or injected intravenously. After subcutaneous transfer into the
      thigh, the greatest number of B cells was detected in the popliteal lymph node
      nearest to the injection site, whereas the lowest number was detected in the
      axillary lymph node opposite to the injection side. Within the first 24 h of
      either intraperitoneal and intravenous injection, B cells were found in
      approximately equal numbers in the lymph nodes and the spleen. Two days later,
      the B-cell distribution in the lymphoid organs appeared to be independent of the
      mode of B-cell transfer. A transient decrease in the numbers of splenic and lymph
      node B cells occurred 9 days after B-cell transfer (a decrease from 70 to 87%)
      prior to the outgrowth of B cells that occurs 21 days after transfer. These
      studies are useful for understanding the numbers of B cells that may be required
      in adoptive transfer studies and their potential cellular interactions at
      particular physiological sites based on the route of cell transfer.

PMID- 9246788
TI  - Biological conversion of lignocellulosic biomass to ethanol.
AB  - The important key technologies required for the successful biological conversion
      of lignocellulosic biomass to ethanol have been extensively reviewed. The
      biological process of ethanol fuel production utilizing lignocellulose as
      substrate requires: (1) delignification to liberate cellulose and hemicellulose
      from their complex with lignin, (2) depolymerization of the carbohydrate polymers
      (cellulose and hemicellulose) to produce free sugars, and (3) fermentation of
      mixed hexose and pentose sugars to produce ethanol. The development of the
      feasible biological delignification process should be possible if lignin
      degrading microorganisms, their echophysiological requirements, and optimal
      bioreactor design are effectively coordinated. Some thermophilic anaerobes and
      recently-developed recombinant bacteria have advantageous features for direct
      microbial conversion of cellulose to ethanol, i.e. the simultaneous
      depolymerization of cellulosic carbohydrate polymers with ethanol production. The
      new fermentation technology converting xylose to ethanol needs also to be
      developed to make the overall conversion process more cost-effective. The
      bioconversion process of lignocellulosics to ethanol could be successfully
      developed and optimized by aggressively applying the related novel science and
      technologies to solve the known key problems of conversion process.

PMID- 9246789
TI  - Lactic acid production in a cell retention continuous culture using
      lignocellulosic hydrolysate as a substrate.
AB  - The effect of lignocellulosic hydrolysate of crushed corn cobs on the kinetics of
      growth and lactic acid production of Lactobacillus casei and L. lactis in the
      cell retention continuous culture was studied. The continuous cultivations were
      carried out in a continuous flow stirred bioreactor combined in a recycle loop
      with an ultrafiltration module retaining all biomass and allowing the continuous
      removal of metabolites, including lactic acid, as a cell-free permeate. Based on
      computer-aided analysis of experimental data, a simple physiological model of
      lactic acid cultivation was developed. The parameters of the model were estimated
      by non-linear regression.

PMID- 9246790
TI  - PolI-driven integrative expression vectors for yeast.
AB  - A novel expression vector for yeast has been constructed from the regulatory
      elements present in the polI promoter and the enhancer/termination region (E/T)
      of rDNA. Under some conditions, this promoter/vector combination produces small
      RNAs such as the hammerhead RNA sequence at levels comparable to polII- and
      polIII-dependent systems. No stable transcription product can be demonstrated
      with this vector when the enhancer/termination sequence is less than 100
      nucleotides downstream from the promoter. On the other hand, high expression of a
      stable, hammerhead RNA molecule can be obtained from this vector by inserting a
      400-bp fragment containing the ADH1 transcription termination region upstream of
      the E/T. RNAs produced by this vector are polyadenylated and multiple copies of
      this plasmid can be stably integrated into the yeast chromosome.

PMID- 9246792
TI  - Biotechnological potential of P450 monooxygenases high-level production of bovine
      cytochrome P450c17 monooxygenase during medium cell density culture of a
      recombinant yeast, Saccharomyces cerevisiae GRF 18 (YEp-Toku1).
AB  - Bovine cytochrome P450c17 monooxygenase was produced in a 30-L fermenter by
      Saccharomyces cerevisiae GRF18 (YEp-Toku1), harboring the GAL10 promoter, and
      using conditions of medium cell density culture. Upon addition of D-galactose as
      an inducer and FeCl3 as a cofactor, cells began to produce the P450 hemoprotein.
      The yield of this enzyme reached a maximum after 31 h but its formation continued
      for more than 60 h after induction. The amount of P450c17 produced was 4.7-fold
      as compared to shake flask experiments.

PMID- 9246791
TI  - The influence of various insect cell lines, p10 and polyhedrin promoters in the
      production of secreted insulin-like growth factor-interleukin-3 chimeras in the
      baculovirus expression system.
AB  - A technique for the optimal synthesis of secreted fusion proteins between insulin
      like growth factors (IGFs) and cytokines is described. The cDNA of BOMIGF, a
      fusion protein between the insect insulin-like peptide bombyxin and IGF II, has
      been linked to the gene of interleukin-3. The BOMIGF-interleukin 3 fusion gene
      was cloned downstream of the promoter regions of the p10 and polyhedrin proteins
      within baculovirus transfer vectors. A third, dual transfer vector was
      constructed with the gene inserted simultaneously behind p10 and polyhedrin
      promoters. Two different lepidopteran cell lines, Spodoptera frugiperda (Sf9) and
      Trichoplusia ni (BTI-TN-5B1-4) were infected with the recombinant baculoviruses
      obtained from the three transfer vectors. Trichoplusia ni cells produced the
      largest amount of recombinant protein. Although the efficiency of the three
      recombinant viruses was remarkably similar, the baculovirus with the gene present
      behind both promoters produced relatively more recombinant protein in host cells
      than those viruses driven with the polyhedrin or p10 promoters alone. The BOMIGF
      interleukin-3 chimera was stable and continuously increased in the culture medium
      up to 5-6 days postinfection. Therefore the addition of a protease inhibitor was
      useful only at the stage of massive host cell death. Medium supplemented with
      copper sulfate was detrimental for the long-term production of the fusion
      protein.

PMID- 9246793
TI  - Addiction specialists and the AHCPR Smoking Cessation Clinical Practice
      Guideline.

PMID- 9246794
TI  - Sir Austin Bradford Hill: medical statistics and the quantitative approach to
      prevention of disease.
AB  - Sir Austin Bradford Hill (1897-1991), son of a prominent medical physiologist,
      was destined for the study of medicine when World War I intervened. He chase to
      enlist as a pilot in the Royal Navy Air Service. Having contracted tuberculosis
      on his way to the Dardanelles, Hill was 'sent home to die'. In spite of the odds
      he recovered; but with no chance of working in physically taxing fields such as
      medicine or science. Advised and encouraged by Major Greenwood, he carved out for
      himself a career in medical statistics, first at the Medical Research Council and
      subsequently at the London School of Hygiene and Tropical Medicine, where his
      inspired teaching helped to shape the development of medical research in the
      second half of the twentieth century. He is particularly remembered for the way
      he made medical statistics an essential part of modern epidemiology, a new phase
      in an epidemiology concerned with chronic as well as with infectious diseases. At
      the same time, he introduced randomization where therapies-beginning with
      streptomycin in tuberculosis-could be evaluated in large-scale clinical trials.
      Perhaps his best known achievement is his design of the smoking and lung cancer
      trials, carried out with Richard Doll who later extended-and still extends-the
      trials which so convincingly have linked addiction to tobacco to patients' later
      problems with cancers and with coronary heart disease.

PMID- 9246796
TI  - Heroin smoking by 'chasing the dragon': origins and history.
AB  - The history of heroin smoking and the subsequent development and spread of
      'chasing the dragon' are examined. The first heroin smoking originated in
      Shanghai in the 1920s and involved use of porcelain bowls and bamboo tubes,
      thereafter spreading across much of Eastern Asia and to the United States over
      the next decade. 'Chasing the dragon' was a later refinement of this form of
      heroin smoking, originating in or near Hong Kong in the 1950s, and refers to the
      ingestion of heroin by inhaling the vapours which result when the drug is heated
      typically on tin-foil above a flame. Subsequent spread of 'chasing the dragon'
      included spread to other parts of South East Asia during the 1960s and 1970s, to
      some parts of Europe during the late 1970s and early 1980s, and to much of the
      Indian sub-continent during the 1980s. At the time of writing, 'chasing the
      dragon' has now been reliably reported from many parts of the world but not from
      others with an established heroin problem-such as the United States and
      Australia. The significance of this new form of heroin use is examined, including
      consideration of the role of the different effect with this new form of use, the
      different types of heroin, and changing public attitudes to injecting.

PMID- 9246795
TI  - Treating grouped data as continuous in alcohol consumption measures.
AB  - In quantity-frequency methods used for self-report measurement of alcohol intake
      (or other exposures), respondents mark the appropriate ranges, e.g. '5 to 8
      drinks', '5 or 6 times per week'. To calculate average consumption only single
      values, not ranges, can be multiplied, and midpoints are commonly used. This
      results in bias if the range lies in the tail of a distribution, as often happens
      with drinks per occasion. The same bias occurs when risk, for example, is plotted
      against consumption levels, which inevitable are grouped into ranges.
      Consequently, estimates of aggregate consumption can be exaggerated and curves of
      risk against exposure level can be misleading. A method is described to calculate
      a relatively unbiased representative value for a range, requiring only knowledge
      of the normal distribution table, the log-normal distribution, and basic
      arithmetic. Part of the procedure is also useful for estimating percentile points
      in data that have been grouped differently, such as income in dollar groups.

PMID- 9246797
TI  - Transitions between routes of benzodiazepine administration among heroin users in
      Sydney.
AB  - A sample of 312 heroin users were interviewed regarding their benzodiazepine use.
      The majority (94%) had used benzodiazepines, 72% in the 6 months prior to
      interview. Benzodiazepine injecting was common, with 28% of the sample having
      injected these drugs, 13% in the 6 months preceding interview. Current
      benzodiazepine injectors showed greater polydrug use, injection-related HIV risk
      taking behaviour, criminal involvement, psychological distress and injection
      related health problems, as well as poorer general health, and an increased risk
      of having overdosed, than other users of benzodiazepines. Of those subjects who
      had injected benzodiazepines, 55% were no longer current benzodiazepine
      injectors. Concern for general health emerged as the most common reason for
      having made a transition away from injecting, and for being likely to make such a
      transition.

PMID- 9246798
TI  - Use of the Nottingham Health Profile for measuring health status of patients in
      methadone maintenance treatment.
AB  - This study was conducted to assess changes in health-related quality of life over
      a 3-year follow-up period in a cohort of 135 opioid dependent patients using the
      Nottingham Health Profile (NHP) questionnaires. Data obtained at 12 months from
      80 patients retained in the programme are presented. In summary, opioid addicts
      in a methadone maintenance programme for a 12-month period experienced an early
      and substantial improvement in health-related quality of life. The use of the NHP
      questionnaire to monitor changes in the subjective health of opioid-dependent
      patients over time provides new insights in the assessment of treatment
      effectiveness of methadone maintenance programmes.

PMID- 9246799
TI  - Assessment of cocaine use with quantitative urinalysis and estimation of new
      uses.
AB  - Qualitative urinalysis methods of monitoring cocaine use may over-detect
      frequency of use, possibly decreasing the ability of clinical trials to detect
      effective treatments. Quantitative urinalysis and newly developed criteria for
      identifying new cocaine use were evaluated as alternative measures of cocaine
      use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking
      subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the
      cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods.
      Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to
      identify occasions of new cocaine use. Results were compared to known cocaine
      administrations in the laboratory study and to self-reported drug use and
      qualitative urinalysis for subjects in the clinical trial. New Use criteria
      correctly identified cocaine administrations in the cocaine dosing study in all
      but a small number of specimens. In the clinical trial, quantitative urinalysis
      and estimated New Uses provided more information about patterns and frequency of
      use than qualitative urinalysis in the different treatment conditions in the
      clinical trial. Interpretation of quantitative urinalysis with New Use rules
      appears to be a useful method for monitoring treatment outcome and may be more
      accurate than traditional qualitative urinalysis in estimating frequency of
      cocaine use.

PMID- 9246800
TI  - Drinking, the majority fallacy, cognitive dissonance and social pressure.
AB  - In drinking and drug surveys, peers are perceived as drinking more and using more
      drugs than the respondent. Particularly in youth studies, this majority fallacy
      is often interpreted as an indication of peer pressure toward drinking and drug
      use. However, exaggerating the alcohol and drug behaviours of significant others
      may be a way of reducing cognitive dissonance. The behaviour of most people
      deviates from their ideal norms. The ensuing dissonance can be alleviated by
      introducing the behaviour of others as a third element in the cognitive field.
      Data from three Scandinavian surveys support the following two predictions based
      on the theory of cognitive dissonance: (1) The tendency to report that other
      people drink more than oneself is more marked in restrictive than in permissive
      communities. (2) On each level of alcohol intake, the tendency to report that
      other people drink more than oneself is stronger among respondents having
      negative alcohol attitudes than among respondents with positive attitudes to
      alcohol. The need to alleviate the cognitive dissonance caused by a discrepancy
      between actual behaviour and normative standards is thus one of the mechanisms
      generating the majority fallacy: "I may not be perfect, but other people are
      still worse". Feeling better than others does not necessarily amount to a
      pressure to turn bad.

PMID- 9246801
TI  - Access to alcohol from licensed premises during adolescence: a longitudinal
      study.
AB  - Control of young people's access to alcohol via licensed premises has been shown
      to be an effective alcohol harm reduction strategy in the United States. In a
      longitudinal study of young New Zealanders their access to alcohol at the ages of
      15 and 18 years was shown to be significantly predictive of the quantities of
      alcohol they consumed during a drinking occasion both then and in subsequent
      years. In turn the quantities of alcohol consumed were predictive of the
      respondents' experience of intoxication related adverse consequences. The impact
      of access via licensed premises on drinking and related problems was greater in
      this cohort of young people than the impact of peer or parental influences.

PMID- 9246802
TI  - Cognitive impairment among the dually-diagnosed: substance use history and
      depressive symptom correlates.
AB  - The present study examined the effects of substance use history and depressive
      symptomatology on the cognitive functioning of 149 male and 72 female dually
      diagnosed inpatients. Logistic regression models examined the effects of life
      time alcohol and cocaine use, previous month's alcohol and cocaine use and
      depression on abstract reasoning as assessed by the Shipley Institute of Living
      Scale (SILS) and neuropsychological functioning as measured by the Screening Test
      for the Luria-Nebraska Neuropsychological Battery (ST-LNNB). Results indicated
      differential effects of substance use across the two cognitive outcome measures.
      Specifically, a significant relationship was demonstrated for previous month's
      alcohol use on Shipley classification. However, after adjusting for possible
      borderline cases, previous month's alcohol use dropped to non-significance and in
      its stead an association between Shipley classification and life-time use was
      demonstrated. No significant effects were demonstrated for cocaine use, recent
      alcohol use, depressive symptoms or any of the interaction terms. The Luria
      Nebraska performance classifications were significantly associated with both
      educational level and life-time cocaine use. No significant relationships were
      obtained for previous month's cocaine use, the alcohol use variables, depressive
      symptoms, or any of the interactions terms. The degree of classification
      agreement between the two outcome measures was slightly better than chance (kappa
      = 0.24 for ST-LNNB and traditional or full scale SILS; kappa = 0.35 for ST-LNNB
      and modified SILS). These kappa coefficients suggest that the SILS and ST-LNNB
      assess partially independent dimensions of cognitive functioning. The findings
      are discussed in light of previous research and implications for clinical
      assessment and treatment are outlined.

PMID- 9246803
TI  - Liquid chromatographic determination using lanthanides as time-resolved
      luminescence probes for drugs and xenobiotics: advantages and limitations.
AB  - Lanthanide sensitized luminescence is a very attractive alternative to UV
      detection and other luminescence techniques, i.e., fluorescence and
      phosphorescence, in separation science for the detection of drugs and xenobiotics
      because of the large Stokes shift, narrow emission bands and long lifetime. Some
      published applications of HPLC determination with lanthanide (Ln3+) sensitized
      luminescence detection are reviewed. Advantages and limitations of this technique
      are discussed. Normal-phase (NP) HPLC is not influenced by the quenching effect
      of water whereas reversed-phase (RP) HPLC is applicable to more compounds than NP
      HPLC. However, pH adjustment and the quenching effect of water on Ln3+
      luminescence are the main drawbacks of RP-HPLC. Elution properties and the need
      for pH adjustment are two arguments for selecting the mode of addition of Ln3+,
      i.e., pre- or post-column in the HPLC system. Sensitized Ln3+ luminescence
      detection is a much more specific method of detection than UV or fluorescence
      detection after HPLC separation but nevertheless, in some cases, does not always
      exhibit a significant increase in analytical performance when the donor itself is
      a strong fluorophore. The development of more powerful excitation sources could
      improve the limit of detection of the Ln3+ sensitized detection technique. This
      review suggests that it would be useful to obtain predicting factors about the
      drug to establish whether the latter is suitable to be measured using an HPLC
      Ln3+ approach.

PMID- 9246804
TI  - Analytical methods for the determination of platinum in biological and
      environmental materials. A review.

PMID- 9246805
TI  - Sampling intercomparisons for aldehydes in simulated workplace air.
AB  - Thirty one laboratories of various EU Member States have participated in two
      interlaboratory comparisons in order to assess errors of personal sampling
      methods associated with both the sampling and the analytical steps. In contrast
      to conventional quality control schemes, this project particularly focuses
      attention on the sampling and identification step; it is executed by means of
      sampling exercises and has included discussions on potential sources of error. In
      a sampling exercise, participants come to a central facility and perform
      measurements on synthetic workplace air in a laboratory installation.
      Concentration levels of formaldehyde, acrolein, glutaraldehyde and acetaldehyde
      between 0.1 and 2 times the limit value for workplace air were prepared at
      various humidity levels and with acetone, occasionally, as interferent. Sampling
      times varied from 1-4 h. The related analytical work is performed at the
      analyst's own laboratory. The intention is for each participant to determine the
      observed value of the delivered standard atmosphere using the sampling method of
      his own choice. Trueness (bias), precision and relative overall uncertainty of
      each method-laboratory combination is calculated and verified towards compliance
      with EN 482, which outlines minimum performance criteria. The first challenge
      involved the precise gas phase generation of the selected analytes in high air
      flows (up to 300 1 min-1) and calculating the true value only by direct reference
      to primary standards. This was accomplished by modifying the capillary dosage
      injection technique so that reactive compounds, like low molecular mass
      aldehydes, could be dosed with the same accuracy and precision as unreactive
      solvents. A permeation tube with high emission rate was developed for
      formaldehyde. Up to ten different sampling techniques were evaluated. The
      measurement methods used by the majority of the participants were based on pumped
      sampling on silica cartridges (or tubes) and glass fiber filters, coated with 2,4
      dinitrophenylhydrazine. It was observed that for formaldehyde, and in some cases
      for acetaldehyde and glutaraldehyde, the majority of the method-laboratory
      combinations complied with an overall uncertainty of 30%. The results for
      acrolein, however, indicated a systematic negative bias, often larger than minus
      50% of the true value, caused by the decomposition of the acrolein DNPH
      derivative in the presence of excess acid and excess DNPH.

PMID- 9246806
TI  - Sampling and analytical quality control of the determination of aluminium in
      soybean leaves.
AB  - A pot trial was set up with nine soil types, each replicated five times, in
      randomized blocks, to investigate the effect of soil properties on the uptake of
      Al by soybean plants. The variance of the measurements was estimated using five
      replicates of each soil type. This then enabled the statistical significance of
      the difference between results for each soil type to be established. The
      analytical variance was determined by two analyses per pot. Systematic errors
      during the analytical procedure were estimated by the analysis of reagent blanks
      and CRMs. Analysis of variance (ANOVA) was used to estimate the proportions of
      total variance contributed by analysis, sampling and geochemistry. Robust
      statistics were required because of the high sensitivity of classical ANOVA to a
      small number of outlying values, due to either technical or geochemical causes.
      In the case study described here, traditional analytical quality control
      apparently gave a satisfactory result. However, the results from robust ANOVA
      showed that the sampling error was the limiting factor for this application. It
      is suggested that the environmental analyst must consider errors from procedures
      of both sampling and analysis of environmental samples.

PMID- 9246807
TI  - Solid-phase extraction of phenols and pesticides in water with a modified
      polymeric resin.
AB  - A comparative study of a chemically modified polymeric resin which has a benzoyl
      group and several commercial sorbents, such as PLRP-S, Envi-chrom P and LIChrolut
      EN, for the solid-phase extraction of various phenolic compounds and pesticides
      was carried out. Selectivity and breakthrough volumes for these compounds with
      different sorbents were studied by coupling an on-line solid-phase extraction
      system with a modified liquid chromatograph equipped with a UV detector. After
      determining the chromatographic conditions, linearity range and detection limits,
      the method was applied to the determination of these compounds in drinking and
      surface water. For 25 ml of sample, the recovery was > 70% for all the compounds,
      except for 4-nitrophenol (62%), and detection limits were between 0.2 and 0.8
      microgram I-1.

PMID- 9246808
TI  - Evaluation of hydromatrix and magnesium sulfate drying agents for supercritical
      fluid extraction of multiple pesticides in produce.
AB  - The simultaneous extraction of relatively polar and nonpolar pesticides has been
      problematic in multiresidue analysis using supercritical fluid extraction (SFE)
      with carbon dioxide. In fruit and vegetable samples, which typically contain 80
      95% water, moisture acts to increase SFE recoveries of many polar pesticides, but
      a drying agent should be used to control water in SFE. Hydromatrix, a prevalent
      drying agent, has many desirable characteristics, but it reduces recovery of
      certain important pesticides, such as methamidophos, acephate, and omethoate.
      MgSO4 has been shown previously to be applicable for the extraction of
      methamidophos and six other pesticides, but MgSO4 has practical disadvantages in
      its use. In this study, properties and SFE results with the individual drying
      agents and their combination were evaluated. Simultaneous recoveries for polar
      and nonpolar pesticides were achieved for 71 pesticides fortified in apple using
      a mixture of 2 + 1 + 2 MgSO4-H2O-Hydromatrix-sample for extraction. The
      advantages of each drying agent were maintained by their combination. The
      analysis of real samples, however, showed that more study was needed to improve
      recoveries of nonpolar pesticides.

PMID- 9246809
TI  - Selective precipitation separation and inductively coupled plasma mass
      spectrometric determination of trace metal impurities in high purity silver.
AB  - A simple and rapid method for the determination of some trace element impurities
      in high purity silver, combining the isolation of analytes from the silver matrix
      with selective precipitation followed by ICP-MS determination was developed. On
      the basis of an extreme difference in the solubilities of the chlorides of silver
      and the other accompanying trace elements, silver can be separated completely
      through the addition of hydrochloric acid. The sample of silver was at first
      dissolved in 7 M nitric acid followed by addition of hydrochloric acid to remove
      the silver matrix by formation of a silver chloride precipitate, while leaving
      the trace element impurities in the solution, which was subsequently analysed by
      ICP-MS. Eleven elements (Al, Au, Cd, Co, Cu, Fe, Mg, Mn, Ni, Pb and Sn) were
      determined with good accuracy and precision. The limits of detection (based on
      the 3 sigma criterion) of these elements were 10(-1)-10(-3) ng g-1. The proposed
      method was successfully applied to the determination of metal impurities in high
      purity silver samples (EM9465 and EM 9343) and validated by the analysis of NIST
      SRM 8171 (Fine Silver FS 14).

PMID- 9246811
TI  - Modified fluorimetric assay for estimating ampicilloate concentrations and its
      use for detecting beta-lactamase and penicillin acylase activity in bacteria.
AB  - Sodium ampicilloate concentrations were estimated fluorimetrically by heating
      solutions with ascorbic acid, EDTA and a modified Lowry A reagent which was
      prepared by including copper sulfate and potassium sodium tartrate in 0.5 mol dm
      3 acetate buffer at pH 4. A concentration range of 0.5-50 mumol dm-3 was used for
      the estimations. The reaction was used to estimate beta-lactamase activity on
      ampicillin but the substrate also showed some fluorescence and a calculation was
      required to determine the amount of ampicilloate formed when both substances were
      present in the one reaction mixture. The beta-lactamase was inhibited by
      treatment with trichloroacetic acid so the procedure could be used to assay the
      enzyme activity after a fixed time. 6-Aminopenicillanic acid did not fluoresce on
      treatment with the modified reagent and organisms which contained penicillin
      acylase lowered the amount of ampicillin which could be converted to
      ampicilloate. When penicillin acylase and beta-lactamase co-existed in the one
      organism, the respective activities were determined by use of the copper
      ascorbate-EDTA fluorescence assay for ampicilloate coupled with a fluorescamine
      assay for 6-aminopenicillanic acid determinations. On prolonged incubation, some
      organisms containing penicillin acylases lowered the amount of ampicilloate which
      formed a fluorescent product. This effect was attributed to deacylation of
      ampicilloate by the penicillin acylases.

PMID- 9246810
TI  - Clean method for the simultaneous determination of propyphenazone and caffeine in
      pharmaceuticals by flow injection Fourier transform infrared spectrometry.
AB  - A procedure is proposed for the simultaneous FTIR determination of propyphenazone
      (PFZ) and caffeine (CAF) in pharmaceuticals. The method involves the dissolution
      of the active principles in CHCl3, followed by filtration of sample solutions to
      remove the excipients. PFZ is then determined by absorbance measurements at 1595
      cm-1, using a baseline established between 2000 and 890 cm-1, and CAF by using
      the first-derivative values at 1712 cm-1, using solutions of PFZ and CAF for
      external calibration. The method was applied in both the stopped-flow and flow
      injection modes, providing precise and accurate results for the analysis of real
      samples. The incorporation of a distillation unit for the on-line recycling of
      the CHCl3 used as carrier and solvent provides an environmentally friendly
      analytical methodology which makes possible an injection frequency of 120 samples
      h-1 and reduces the cost and side-effects of the production of laboratory waste.

PMID- 9246812
TI  - Study of a lanthanide fluorescence system with a coupled reaction based on hemin
      catalysis.
AB  - The oxidation reactions of three substrates, p-hydroxybenzoic acid (HBA), p
      hydroxyphenylacetic acid, and p-hydroxyphenylpropionic acid, with H2O2 catalysed
      by hemin were studied. It was significant that only the oxidation product of HBA,
      di-p,p'-hydroxybenzoic acid, forms a long-lived fluorescent complex with Tb3+.
      The three substrates themselves do not form fluorescent complexes with Tb3+
      although they have chemical structural similarities. Based on this, a novel
      lanthanide fluorescence system with a coupled reaction was developed. The
      possible reactive mechanism is discussed. HBA was concluded to be well suited to
      several types of application from hemin determination to bovine serum albumin
      labeling.

PMID- 9246813
TI  - Spectrophotometric determination of carbamate pesticides with diazotized
      trimethylaniline in a micellar medium of sodium dodecyl sulfate.
AB  - The spectrophotometric determination of the carbamate pesticides carbaryl,
      bendiocarb, carbofuran, methiocarb, promecarb and propoxur is proposed. The
      pesticides are hydrolyzed in alkaline medium to 1-naphthol or phenolates, which
      are coupled with diazotized trimethylaniline (TMA) in a sodium dodecyl sulfate
      micellar medium to form the azo dyes. The micellar medium increased the
      solubility of TMA and enhanced the sensitivity. The performance of TMA was
      compared with that of sulfanilic acid, which is the conventional reagent used in
      these determinations. Although the absorbance of the azo dyes of sulfanilic acid
      was also enhanced in the micellar solution, the sensitivity was still greater
      with TMA. Further, at the pH required for the coupling reaction (9.5), the
      absorbance of the blank was negligible with TMA but large with sulfanilic acid.
      Using TMA, the limits of detection were in the range 0.2-2 micrograms cm-3. The
      procedure was applied to the determination of carbaryl in spiked tap, river and
      pond water samples and to the evaluation of various carbamates in commercial
      pesticide formulations.

PMID- 9246815
TI  - Identification of endogenous 19-nortestosterone in pregnant ewes by gas
      chromatography-mass spectrometry.
AB  - Considered as a xenobiotic for many years, 19-nortestosterone has been
      extensively studied. Analyses developed to control the illegal use of this
      steroid in meat-producing animals led researchers to demonstrate the endogenous
      presence of 19-nortestosterone in several species. In this paper, the natural
      occurrence of 19-nortestosterone in its alpha form (epinandrolone) in the urine
      of pregnant sheep was demonstrated using gas chromatography-mass spectrometry.
      This reference method allowed 17 alpha-nandrolone to be detected and identified,
      and the absence of the beta epimer in the urine of pregnant sheep to be
      demonstrated. 17 alpha-Nandrolone was accurately determined at different stages
      of pregnancy. The analyses showed that epinandrolone, which was not detectable in
      the urine of non-pregnant sheep, was excreted in small amounts (leading to a <
      0.5 ppb concentration) during the first 4 months of pregnancy. 17 alpha
      Nandrolone concentrations then increased during the last month until parturition.
      The origin of this molecule was not determined.

PMID- 9246814
TI  - Vitamin K in milk and infant formulas: determination and distribution of
      phylloquinone and menaquinone-4.
AB  - A method is described for the determination of phylloquinone and menaquinones
      following enzymatic digestion, extraction and a single-stage HPLC technique
      utilizing post-column reduction with zinc and fluorescence detection. The
      technique is applicable to both routine compliance control of phylloquinone
      supplemented infant formula powders (30-150 micrograms per 100 g) and fundamental
      studies of the K vitamins at endogenous levels in fluid milks (0-5.0 micrograms
      per 100 g). Analytical figures of merit include a detection limit of 30
      micrograms on-column, recoveries greater than 98% for both K1 and MK4, an RSDR of
      2.35% (K1) and 2.32% (MK4) and a regression correlation of 0.9932 for a wide
      range of infant formulas when compared against an alternative HPLC-UV technique.
      MK4 and 2',3'-dihydrophylloquinone, both with undefined bioactivity, were
      detected at measurable levels in a range of infant formulas. Although the higher
      menaquinones were found to be essentially absent in the milk of several species,
      the significant presence of MK4 relative to K1 has been confirmed in all milks
      examined, with both dominant forms correlated during early lactation in the cow.
      These observations suggest an as yet unrecognized physiological function for MK4
      in infant nutrition.

PMID- 9246816
TI  - 4-(5',6'-Dimethoxybenzothiazolyl)benzoyl fluoride and 2-(5',6'
      dimethoxybenzothiazolyl)benzenesulfonyl chloride as sensitive fluorescence
      derivatization reagents for amines in high-performance liquid chromatography.
AB  - 4-(5',6'-Dimethoxybenzothiazolyl)benzoyl fluoride (BHBT-COF) and 2-(5',6'
      dimethoxybenzothiazolyl)-benzenesulfonyl chloride (BHBT-SOCI) have been developed
      as highly sensitive and selective fluorescence derivatization reagents for
      primary and secondary aliphatic amines in HPLC. These reactivities were
      investigated using n-propylamine, n-heptylamine and N-methylhexylamine as model
      compounds to optimize the derivatization conditions. Both reagents readily
      reacted with the amines in basic media to give the corresponding fluorescent
      derivatives, which were separated isocratically by reversed-phase (C18) liquid
      chromatography with aqueous methanol. The detection limits (signal-to-noise ratio
      = 3) of BHBT-COF for primary and secondary amines are approximately 3 and 30
      fmol, respectively, and those of BHBT-SOCI are approximately 3 and 300 fmol,
      respectively, for an injection volume of 20 microliters. Both reagents gave no
      fluorescent derivatives for aromatic amines.

PMID- 9246817
TI  - Enzyme immunoaffinity chromatography--a rapid semi-quantitative immunoassay
      technique for screening the presence of isoproturon in water samples.
AB  - Immunochromatography devices based on the principles of affinity chromatography
      and enzyme immunoassay have been developed to illustrate the possibility of
      providing extra-laboratory 'in the field' tests for pesticide monitoring.
      Isoproturon was chosen in this study as an example though other pesticides could
      have been used provided a suitable antiserum existed. The test system was
      prepared by immobilising isoproturon antibodies to porous silica which were then
      packed into disposable columns (immunoaffinity columns). The addition of
      chromagen-substrate 3,3',5,5'-tetramethylbenzidine into the immunoaffinity
      columns, after the application of a mixture containing an equal volume of
      isoproturon samples or isoproturon standard solutions with a fixed concentration
      of isoproturon labelled with horseradish peroxidase, allowed the development of a
      colorimetric portable assay capable of screening samples qualitatively for the
      presence of isoproturon in water. Samples with contamination levels of 0.12
      microgram l-1 isoproturon and above were visually identified as positive samples
      in comparison to the zero standard sample. However, samples with concentrations
      below this level would be considered as negative (no isoproturon present at this
      limit of detection). The duration of the sample screening procedure on the column
      was less than 25 min making the technique highly suitable for a rapid estimate of
      isoproturon concentrations. Furthermore, the system could estimate isoproturon
      concentrations in water from various sources with no requirement for sample
      preparation. Therefore, the technique is ideally suited for monitoring the
      presence of pesticides in water. Further refinement of the assay could result in
      a test suitable for use by non-skilled personnel in extra-laboratory locations
      (e.g., a mobile or field laboratory).

PMID- 9246818
TI  - Amperometric bienzymic sensor for aspartame.
AB  - An amperometric enzyme electrode for the determination of aspartame was developed
      by covalent immobilization of alcohol oxidase and alpha-chymotrypsin. A platinum
      based hydrogen peroxide electrode was used as the detector. Excellent sensitivity
      was obtained using batch, flow-through and flow injection methods with detection
      limits of 2 x 10(-7), 4 x 10(-7) and 10(-6) mol l-1, respectively. Different
      strategies for eliminating interfering compounds, including the introduction of
      an additional alcohol oxidase-catalase membrane and signal subtraction using an
      alcohol electrode, were employed. A recovery study on seven food samples was
      carried out and the results were satisfactory.

PMID- 9246819
TI  - Potentiometric and coulometric titration of 6-propyl-2-thiouracil.
AB  - A method for the determination of 6-propyl-2-thiouracil involving its reaction
      with iodine in an alkaline medium is presented. In volumetric titration with
      potentiometric end-point detection, the range of determination is 125-500 mumol
      (21-85 mg). In coulometric titration using biamperometric end-point detection,
      0.5-5.0 mumol (0.085-0.85 mg) of 6-propyl-2-thiouracil was successfully
      determined. The RSD in all applied techniques was < 1%. The methods developed
      were applied to the determination of 6-propyl-2-thiouracil in tablets.

PMID- 9246820
TI  - Handling false negatives, false positives and reporting limits in analytical
      proficiency tests.
AB  - The Harmonised Protocol on proficiency testing produced by ISO, IUPAC and AOAC
      International recommends that participants' results on interval or ratio scales
      are converted to z-scores for assessment. When proficiency tests are conducted
      with materials that contain little or no analyte (simulating real conditions in
      residue analysis) scheme organisers have reported difficulty with applying the z
      scoring system when false negatives and false positives occur. This paper
      concludes that the z-scoring system is adaptable without change to false
      negatives and positives, although a degree of statistical expertise is called
      for.

PMID- 9246822
TI  - [The 6 minutes test in heart failure].

PMID- 9246821
TI  - [Complex heart diseases. From concept to evolution].

PMID- 9246824
TI  - [Relationship between mitral valve prolapse and arrhythmogenic right ventricular
      disease].
AB  - PURPOSE: To evaluate some features of ventricular arrhythmias in patients with
      mitral valve prolapse. METHODS: We studied 25 patients (female: 19; mean age: 37
      +/- 13 years) with ventricular arrhythmias, mitral valve prolapse and normal
      ventricular function. All patients underwent a 24h Holter and high resolution ECG
      (HRECG). The Qtc intervals were measured in lead II (normal < 0.44 s). In order
      to define the possible origin of the ventricular focus, the morphology of the
      ectopic beats were analysed in leads I, II, aVF, V1 using the following criteria:
      1) LBBB morphology with left axis deviation in the frontal plane (FP): origin at
      the inflow tract of the right ventricle (RV); 2) LBBB morphology with right axis
      deviation in the FP: origin at the outflow tract of the RV; 3) RBBB morphology
      with left axis deviation in the FP: origin at the posterior region of the left
      ventricle (LV). RBBB morphology with right axis deviation in the FP: origin at
      the anterior region of the LV. RESULTS: Twenty three (92%) patients showed > 720
      isolated ventricular ectopic beats/24 h. Paired ventricular response was detected
      in 18 (72%) patients and non-sustained VT in 15 (60%). HRECG was positive in six
      (24%) patients and Qtc interval was prolonged in 13 (52%). RV was the site of
      origin of the ventricular ectopic beats in 85% of the patients (outflow: 85%;
      inflow: 15%). Only five (20%) patients had arrhythmias from the LV. CONCLUSION:
      There was a high incidence of ventricular arrhythmias with a low incidence of
      positive HRECG tests, suggesting that the mechanisms of the arrhythmias do not
      correlate with slow intramyocardial conduction. It was noted a strong association
      between mitral valve prolapse, arrhythmogenic right ventricular disease and Qtc
      prolongation. It is possible that in some of this patients the finding could
      represent a global myocardial disease.

PMID- 9246825
TI  - [Clinico-pathological correlation in the indeterminate form of experimental
      Chagas' disease in dogs].
AB  - PURPOSE: To study the functional cardiac component of the indeterminate form of
      experimental Chagas' disease in dogs. METHODS: Four dogs chronically infected
      with Trypanosoma cruzi and eight normal controls were used. They were submitted
      to several invasive procedures, either in the presence of complete autonomic
      block or not, to test for disturbances in the origin and conduction of electric
      stimuli and the function of cardiac muscle. Histological examination of the heart
      and its conduction systems was performed in all animals. RESULTS: Mild to
      moderate focal myocarditis was found in infected dogs, often involving the
      conduction system of the heart. Sections of the heart from control dogs were
      histologically normal. Functional data on excitability, intra and interatrial
      conduction time and sinus node recovering time were essentially similar for both
      infected and control animals. CONCLUSION: Focal myocarditis, the hallmark of the
      indeterminate form of Chagas' disease, did not alter the normal parameters of
      cardiac function, as seen after investigation with sensitive invasive techniques.
      It is probable that subjects considered as belonging to the indeterminate form of
      Chagas' disease, but presenting mild alterations at sensitive exploratory tests,
      may have more severe lesions than that usually described or may be already in the
      early progressive cardiac form of the disease.

PMID- 9246823
TI  - [Results of aortic stenosis surgery in patients with severe ventricular
      dysfunction].
AB  - PURPOSE: To study the short and long term clinical course of patients with severe
      aortic stenosis after surgical treatment of the valvular lesion. METHODS: Thirty
      survivors among 31 consecutive patients with severe left ventricular dysfunction
      (LVD) due to aortic stenosis (AS) were submitted to clinical and
      echocardiographic follow-up during a mean of 30 months after surgical treatment
      of the valvular lesion. Twenty five (83.3%) patients were male with a mean age of
      50 years (25 to 74). Before operation the following parameters were obtained:
      diastolic left ventricular diameter (DLVD), shortening fraction (SF), left
      ventricular ejection fraction (LVEF), aortic valve area (AVA), left ventricular
      aortic pressure gradient (PG) and NYHA functional class (FC). During the follow
      up, after the surgical procedure, FC, DLVD, LVEF and SF could be analysed and
      compared with previous data. RESULTS: A significant rise in SF (p = 0.001) and
      LVEF (p = 0.0001), as well as a decrease in DLVD (p = 0.001) were observed in the
      follow up. Symptoms lessened in severity in the majority of patients. Three of
      our patients died with progressive LVD and heart failure, after at least 36
      months of follow-up. These results indicate that when operation is carried out in
      patients with AS and left ventricular failure, a significant improvement in left
      ventricular function and in symptoms takes place. Although the risk of surgical
      treatment is increased in this group of patients, LVD should not be considered a
      contraindication to the procedure. CONCLUSION: The left ventricular dysfunction
      is not a contraindiction for the surgical treatment of the aortic stenosis.

PMID- 9246826
TI  - [Coronary transluminal angioplasty in octogenarians].
AB  - PURPOSE: To evaluate the immediate and long term results of percutaneous
      transluminal coronary balloon angioplasty (PTCA) in patients over 80 years old.
      METHODS: From 1/1/89 to 6/31/95, 97 patients with 80 years of age or older were
      submitted to PTCA and were divided into three groups: group A (GrA)-30 patients
      with stable angina, mean age of 82.5 years, 24 (80%) men; group B(GrB)-40
      patients with unstable angina, mean age 81.2 years, 31 (77.5%) men; group C (GrC)
      27 patients with myocardial infarction (MI), mean age of 82 years, 16 (59.2%)
      men. RESULTS: Early outcome-general success rate of 84.5% and mortality rate of
      5.1%. The success and mortality rate were in GrA 83.3% and 3.3%, in GrB 85% and
      5% and in GrC 85.2% and 7.4%, respectively. Late outcome-the number and
      percentage of patients with late follow-up and the clinic-angiographic and
      angiographic restenosis rates were for GrA 19(76%), 52.9%, 75%; GrB 30(88.2%),
      30.8%, 61.5% and GrC 12(52.2%), 66.6%, 85.7%, respectively. CONCLUSION: PTCA can
      be considered an important revascularization alternative in octogenarian patients
      because of high early success rate, low mortality and acceptable long-term
      outcome.

PMID- 9246828
TI  - Ventriculectomy. A direct application of Laplace's law.

PMID- 9246827
TI  - [Effects of partial ventriculectomy on left ventricular mechanical properties,
      shape, and geometry in patients with dilated cardiomyopathy].
AB  - PURPOSE: To investigate the short-term effects of the partial ventriculectomy
      (resection of lateral wall associated to mitral annuloplasty) on cardiac
      mechanics, contractility, shape and geometry of the left ventricle (LV). METHODS:
      Eleven male patients with severe congestive heart failure due to dilated
      cardiomyopathy were studied. The mean age was 51 +/- 7 years and the functional
      class was III (five patients) or IV (six patients) before the surgery. Patients
      were evaluated before and at 17 +/- 4 days after the surgery by simultaneous LV
      pressure and echocardiographic data. End-diastolic pressure (EDP-mmHg), wall
      stress (EDS-g/cm2) and diameter (EDD-cm); endsystolic wall stress (ESS) and
      diameter (ESD), fractional shortening (FS-%) and maximal elastance (Emax-mmHg/
      cm/s); the diastolic slope of the pressure-diameter (Kp-mmHg/cm) and stress
      strain (Km-g/cm2) loops; shape (L/ EDD, adimensional, where L is the LV long
      axis) and geometry (Th/EDD, adimensional, where TH is the LV diastolic thickness)
      were obtained. RESULTS: 1) The ressected muscle fragments (diamond shape) were
      10.8 +/- 1.3 cm in length and 5 +/- 0.6 cm in width; 2) all patients were
      discharged from hospital (15-29 days) in class I (eight cases), II (two), and III
      (one); 3) it was observed a decrease in EDP (24.3 +/- 7.7 x 17.5 +/- 3.2, p =
      0.016); in EDD (8.0 +/- 0.7 x 7.2 +/- 0.8, p = 0.002); in EDS (57.9 +/- 26.8 x
      37.4 +/- 19.2, p = 0.005); in ESS (199 +/- 46.9 x 102.8 +/- 33.1, p = 0.004); in
      ESD (7.1 +/- 0.7 x 5.7 +/- 0.8, p < 0.001); in Kp (22.3 +/- 15.9 x 11.5 +/- 6.9,
      p = 0.014); and in K(m) (467.4 +/- 212 x 214.6 +/- 87.4, p = 0.01); and, 4) it
      was noted an increase in FS (11.5 +/- 1.8 x 19.8 +/- 3.9, p < 0.001); in Emax
      (13.8 +/- 2.2 x 18.6 +/- 3.2, p < 0.001); and in L/EDD (1.32 +/- 0.1 x 1.47 +/-
      0.13, p < 0.007) and Th/Dd (0.11 +/- 0.04 x 0.17 +/- 0.08, p < 0.038).
      CONCLUSION: The partial ventriculectomy showed multiple significant beneficial
      effects in these dilated myopathic hearts.

PMID- 9246829
TI  - [Signs of myocardial ischemia associated with subarachnoid hemorrhage].
AB  - Electrocardiographic changes, left ventricular wall motion abnormalities,
      myocardial ischemia, myocytolysis and arrhythmias have been well documented in
      patients with cerebral bleed. These complications may be related to stimulation
      of autonomic nervous system and central nervous system. We report a case of a 38
      year-old back woman without previous heart disease, taken to emergency unit with
      headache and subarachnoid Haemorrhage. One day after, she complained of
      retroesternal pain. An electrocardiographic tracing showed significant and
      diffuse ST-T wave abnormalities. The patient remained stable with no neurologic
      or cardiac deficits. She was treated with bed rest, nimodipine, isossorbide
      propranolol and is symptomless six months of follow-up.

PMID- 9246830
TI  - [Double origin of anterior descending artery--from the left and right coronary
      arteries--associated with anomalous origin of the circumflex artery].
AB  - A 65 year-old white man, with typical angina pectoris, underwent coronary
      angiography that showed dual left anterior descending artery (LAD), originating
      from the right coronary artery (RCA), associated with anomalous origin of the
      left circumflex artery (LCX) also from the RCA. This an extremely rare coronary
      artery anomaly and, it is the first case reported, so far. This rareness and
      clinical significance are emphasized.

PMID- 9246831
TI  - [Molecular biology of hyperlipidemias. Genetic variation of apolipoproteins].

PMID- 9246833
TI  - Obesity--the inevitable penalty of civilisation?

PMID- 9246832
TI  - [Evaluation of efficacy and safety of etofibrate in primary hyperlipidemia. A
      multicenter study].
AB  - PURPOSE: To evaluate the clinical efficacy of etofibrate in primary
      hyperlipidemia in patients from clinical centers representative of all main
      Brazilian cities. METHODS: One thousand, nine hundred and fourty three
      hyperlipidemic patients were submitted to diet and drug treatment with etofibrate
      (500 mg/day) for eight weeks. The data b WAS analyzed as to changes in the
      lipoprotein profile, as well as the side effects. RESULTS: There was an important
      reduction in total cholesterol (19.88%), triglycerides (29.59%), LDL-c (14.89%)
      and VLDL-c (14.54%) concentration. There was a significant increase in HDL-c
      (18.14%). Adverse effects were observed in 8.5% of the patients, without major
      clinical relevance, however, in 1.44% the treatment had to be interrupted.
      CONCLUSION: Administration of etofibrate promoted positive changes in all
      parameters of the lipid and lipoprotein profile, thus reducing the risk of
      atherosclerotic disease, without significant side effects in the great majority
      of sample studied.

PMID- 9246834
TI  - Assessing obesity: classification and epidemiology.
AB  - Obesity is generally defined as a body mass index (BMI) of 30 kg/m2 and higher.
      Overweight is defined as a BMI between 25 and 30 kg/m2. The prevalence varies
      considerably between countries, and between regions within countries. It is
      estimated that more than half of adults aged 35-65 living in Europe are either
      overweight or obese. Overweight is more common among men than among women but
      obesity is more common among women. The prevalence of obesity in Europe is
      probably in the order of 10-20% in men and 15-25% in adult women. In most
      European countries who have reliable data on time-trends the prevalence of
      obesity seems to be increasing. In most European countries, obesity is usually
      inversely associated with socio-economic status, particularly among women. New
      classifications of overweight may be based on cut-off points for simple
      anthropometric measures which reflects both total adiposity as well as abdominal
      fatness.

PMID- 9246835
TI  - A review of the economic analysis of obesity.
AB  - There are indications that the treatment costs arising from obesity are
      significant. However, the cost-of-illness studies undertaken to data also
      highlight two other important points. First, the cost of treatment in sensitive
      to the body mass index (BMI) cut-off used. Given that there is no definitive
      definition of obesity as based on BMI, a range of costs reflecting differing BMI
      cut-offs may be more appropriate than the use of a single figure. Second, the
      costs are, not surprisingly, also sensitive to the defined associated diseases.
      Again there is little agreement on these and also little information on the
      relative risks of attributable diseases arising from obesity. The calculations of
      the cost-of-illness arising from the treatment of obesity, and its associated
      conditions must, therefore, remain indicative rather than authoritative.

PMID- 9246836
TI  - Aetiology of obesity.
AB  - Obesity is not a single disorder but a heterogeneous group of conditions with
      multiple causes each of which are ultimately expressed as an obese phenotype.
      Fatness does run in families, but the genetic component does not follow simple
      Mendelian principles and the influence of the genotype on the aetiology of
      obesity may be attenuated or exacerbated by non-genetic factors. Body weight is
      ultimately determined by the interaction of genetic, environmental and
      psychosocial factors acting through the physiological mediators of energy intake
      and expenditure.

PMID- 9246837
TI  - Neurobiology.
AB  - The role of neuropeptide Y (NPY), leptin and 5-HT and other neurotransmitters
      implicated in the regulation of energy balance are only now being fully
      investigated. Little is known about how they may interact with each other in this
      complex process. In evolutionary terms, the availability of excess food, and the
      risk of obesity, is only a recent occurrence in humans. Man, and perhaps other
      species, may not have developed a specialised neurochemical system for adjusting
      food intake during obesity. Hence perturbation of a single system, such as
      hypothalamic NPY or leptin, is unlikely to be directly responsible for the
      development of most obesity. In contrast, periods of food deprivation and partial
      starvation have been common in the animal kingdom and the multitude of
      neurotransmitters implicated in energy balance are more likely to be directed
      towards increasing food consumption and conserving energy than reducing appetite
      and increasing thermogenesis in the presence of excess. The last few years have
      witnessed rapid advances in the understanding of the fundamental mechanisms that
      regulate body weight and fat content. This progress will undoubtedly continue in
      the future, and it is hoped that this will be rewarded with the development of
      new drugs to treat obesity. At present, however, it is unclear whether NPY,
      leptin, or other apparently strong candidates will be the winner in the lucrative
      race for the ideal anti-obesity drug.

PMID- 9246838
TI  - Obesity as a disease.
AB  - Obesity is associated with the development of some of the most prevalent diseases
      of modern society. The greatest risk is for diabetes mellitus where a body mass
      index above 35 kg/m2 increases the risk by 93-fold in women and by 42-fold in
      men. The risk of coronary heart disease is increased 86% by a 20% rise in weight
      in males, whereas in obese women the risk is increased 3.6-fold. Elevation of
      blood pressure, hyperlipidaemia and altered haemostatic factors are implicated in
      this high risk from coronary heart disease. Gallbladder disease is increased 2.7
      fold with an enhanced cancer risk especially for colorectal cancer in males and
      cancer of the endometrium and biliary passages in females. Endocrine changes are
      associated with metabolic diseases and infertility, and respiratory problems
      result in sleep apnoea, hypoventilation, arrhythmias and eventual cardiac
      failure. Obesity is not a social stigma but an actual disease with a major
      genetic component to its aetiology and a financial cost estimated at $69 billion
      for the USA alone.

PMID- 9246839
TI  - Obesity, non-insulin-dependent diabetes mellitus and the metabolic syndrome.
AB  - Obesity is characterised by alterations in metabolic function which result from a
      combination of increasing total body fatness and the regional distribution of
      adipose tissue. Abdominal visceral obesity is particularly associated with
      hyperinsulinaemia, increased portal vein free fatty acid concentration, hepatic
      gluconeogenesis, altered adrenocortical activity and androgen secretion and
      reduced plasma sex hormone binding globulin levels. These alterations, which are
      accompanied by changes in visceral adipocyte sensitivity to plasma catecholamine
      stimulation, enhance further visceral fat deposition and the perpetuation of the
      metabolic derangements. The characteristic dyslipidaemia associated with upper
      body obesity and the frequent development of NIDDM are predictable consequences.
      In contrast to the considerable knowledge about the biochemical background to
      these alterations, relatively little is understood about the mechanisms through
      which an individual's ethnic background influences the changes. This chapter
      reviews these important issues.

PMID- 9246840
TI  - Obesity and female reproductive function.
AB  - Obesity has consistently been demonstrated to have a detrimental effect upon the
      female reproductive system. This review explores the common association of
      obesity with polycystic ovary syndrome (PCOS), the effect of obesity on the
      clinical and endocrinological parameters, and the role of insulin resistance in
      the expression of this disorder. An improvement in menstrual function, a decrease
      in the clinical androgenic profile, and significant increase in spontaneous
      pregnancy rates have been reported following weight loss. Obesity is associated
      with poor pregnancy outcome and miscarriage in both women with PCOS, and in those
      with normal ovarian morphology. The optimal weight gain during pregnancy remains
      controversial, but obesity is a risk factor for both maternal and fetal
      complications, and dietary advice should be offered on an individual basis
      according to the pre-pregnancy BMI. Weight gain at the time of menopause is
      common, and dietary advice is paramount as obesity is an independent risk factor
      for thrombosis, coronary heart disease (CHD), and breast and endometrial cancer.
      Effective nutritional counselling should be offered at all stages of the female
      reproductive lifecycle.

PMID- 9246842
TI  - Obesity management by life-style strategies.
AB  - This chapter discusses lifestyle management strategies for obesity in adults and
      is based on an assumption that treatment, resulting in appropriate and sustained
      weight loss, is of benefit to individuals. It examines dietary management
      strategies including the use of very low calorie diets, moderate energy
      restriction and individual and group approaches in commercial and non-commercial
      environments. It explores the role of physical activity in the treatment of
      obesity in particular focusing on the associated health benefits and the
      increasing evidence of the importance of physical activity in weight maintenance.
      It discusses the effect of behavioural interventions on achieving and maintaining
      weight loss and briefly offers suggestions for the organisation of lifestyle
      interventions.

PMID- 9246841
TI  - Key issues in the prevention of obesity.
AB  - Obesity is a serious, chronic medical condition which is associated with a wide
      range of debilitating and life-threatening conditions. It imposes huge financial
      burdens on health care systems and the community at large. Obesity develops over
      time and once it has done so, is difficult to treat. Therefore, the prevention of
      weight gain offers the only truly effective means of controlling obesity. Very
      little research has directly addressed the issue of obesity prevention and
      previous efforts to prevent obesity amongst individuals, groups or whole
      communities have had very limited success. However, we have learned sufficient
      from past preventive activities to realise that the management of obesity will
      require a comprehensive range of strategies with actions that target those with
      existing weight problems, those at high risk of developing obesity as well as the
      community as a whole. The prevention and management of obesity in children should
      be considered a priority as there is a high risk of persistence into adulthood.

PMID- 9246843
TI  - Present and future pharmacological approaches.
AB  - There is evidence that drugs altering food intake such as dexfenfluramine,
      sibutramine and orlistat have useful therapeutic effects, with an acceptable side
      effect profile. 'Thermogenic' drugs, such as ephedrine and caffeine, are also
      effective, but less well tolerated and may, in any case, work by producing
      anorexia. The state of drug treatment for obesity now is similar to the early
      days of antihypertensive treatment in the 1960s when reserpine, ganglion blockers
      and nonselective adrenergic blocker were all that was available. There is
      considerable reason for optimism that the next 10 years will bring better
      treatments for the obese.

PMID- 9246844
TI  - Surgical treatment for morbid obesity.
AB  - Since severe obesity is frequently associated with serious metabolic,
      cardiovascular and psychological co-morbid conditions, and given the usually
      unsuccessful results of conservative therapeutic approaches, surgical treatment
      based on gastric restriction procedures is increasingly recognized as a treatment
      of choice for morbidly obese persons. Among several surgical approaches designed
      to promote a substantial loss of weight, two gastric restriction procedures, i.e.
      the vertical banded gastroplasty and the gastric bypass, have been increasingly
      used during the past years. Both techniques induce an impressive loss of weight,
      and are surprisingly well tolerated, even by severely obese persons. The usual 50
      75% reduction of initial weight excess, is followed by a clear-cut reduction, or
      even disappearance of, obesity-related co-morbidity, such as hypertension,
      diabetes mellitus or sleep apnea syndrome. While serious peri- and postoperative
      risks are very limited, the intractable vomiting occurring after gastroplasty,
      and potential sequelae related to iron and calcium malabsorption after the
      gastric bypass, represent much more frequent complications of the surgical
      treatment of obesity. There is also a tendency towards a late regain of weight,
      but the benefit in terms of improvement in the obesity-associated co-morbidity is
      in general maintained despite this partial increase in weight. Gastric procedures
      are, therefore, an effective treatment of severe obesity and of its co-morbid
      conditions. However, careful medical and nutritional supervision is necessary
      during the follow-up after surgery, to prevent potential nutritional or digestive
      complications.

PMID- 9246845
TI  - Magnetic source imaging in the human heart: estimating cardiac electrical sources
      from simulated and measured magnetocardiogram data.
AB  - The estimation of pseudo primary current dipoles on a 2D-manifold in the atrial
      and ventricular myocardium and septum, and of the transmembrane potential on the
      endocardium and epicardium, from the magnetic heart field is investigated. The
      human thorax surrounding the heart is modelled by an inhomogeneous boundary
      element volume conductor model, including the outer thorax surface and the
      surfaces of the lungs. The influence of the blood mass is neglected. In the
      inverse problem Tikhonov's regularisation is applied. The regularisation
      parameter is determined by the L-curve method. An algorithm for iterative
      improvement is applied to estimate the pseudo primary current dipoles. Synthetic
      magnetic field and electric potential data are generated using a cellular
      automaton model of the entire human heart. Real world magnetic field data for a
      normal subject are analysed to demonstrate the practicability and effectiveness
      of the presented method.

PMID- 9246846
TI  - Continuous measurements by impedance of haematocrit and plasma volume variations
      during dialysis.
AB  - A technique for continuous measurements of haematocrit and plasma volume in the
      arterial line of dialysed patients has been tested in vitro and in vivo. This
      method uses impedance measurements at 5 kHz and requires a single haematocrit
      measurement. It relies on two assumptions: that plasma resistivity does not
      change during dialysis and that blood resistivity obeys Hanai's model. Both
      assumptions are verified during in vitro tests. Haematocrits measured in vivo by
      this method are found to be in good agreement with direct measurements from blood
      samples. The haematocrit variation is then used to monitor changes in plasma
      volume, assuming conservation of erythrocyte volume. In addition, it is possible
      to obtain the variation in interstitial volume by combining these data with body
      impedance measurements.

PMID- 9246847
TI  - Dielectric properties of some keratinised tissues. Part 1: Stratum corneum and
      nail in situ.
AB  - Blister-skin and warts have been studied as possible sources of 'pure' stratum
      corneum without sweat ducts. The purpose of the study was to assess whether the
      DC electrical conductance measured on human skin is totally dominated by the
      sweat ducts, or is also significantly contributed to by the stratum corneum
      itself. By means of galvanic skin response (GSR) measurements, these tissues were
      found to be unrealiable as sources of 'pure' stratum corneum. This is because
      they displayed significant GSR waves, and hence should have some form of active
      pores. However, measurements on blister-skin and nail in situ revealed a
      substantial frequency independent electrical conductance at frequencies typically
      below 10 Hz.

PMID- 9246848
TI  - Dielectric properties of some keratinised tissues. Part 2: Human hair.
AB  - Some electrical properties of human hair have been investigated to determine
      whether a significant DC electrical conductance is present in keratinised
      tissues. The DC conductance was found to be substantial and highly dependent on
      the moisture level in the hair fibres. At high moisture levels, the conductance
      was found to be almost frequency independent below 1 kHz. Absorption and
      desorption profiles were also monitored, revealing different stages of sorption
      mechanisms in the fibres. Although absorption was found to be a slow process with
      'time constants' in the range of hours, desorption was much faster, in the range
      of a few minutes.

PMID- 9246849
TI  - Quantitative correlations among fibrinogen concentration, sedimentation rate and
      electrical impedance of blood.
AB  - Blood cells from 8 normal subjects, anticoagulated with EDTA, were washed twice
      with saline solution (100 mmol/l) and resuspended into saline solutions of
      different concentrations of human plasma fibrinogen. The erythrocyte
      sedimentation rates (ESRs) of these suspensions were determined by the Westergren
      method, and their resistance Rp and capacitance Cm were determined by measuring
      the impedances at three frequencies 100 kHz, 800 kHz and 1.2 MHz. The results
      showed that the logarithm of the ESR was proportional to the concentration of
      fibrinogen, Fb (g/l), expressed as: ln(ESR) = 0.468Fb - 0.10, (r = 0.96); and the
      haematocrit-normalised resistance R'p and capacitance C'm were both directly
      proportional to the concentration of fibrinogen, R'p = 3.99Fb + 465.0, (r =
      0.87), and C'm = 49.7Fb + 628.2, (r = 0.96). The influence of fibrinogen on the
      impedance might partly be the result of interfacial polarisation and/or of red
      cell rouleaux formation. The results are useful for understanding the mechanism
      of the association between the impedance and the ESR of blood, and for finding
      means of improving the accuracy when estimating the ESR by the electrical
      impedance method.

PMID- 9246850
TI  - Influence of synchronous and sequential stimulation on muscle fatigue.
AB  - In acute experiments the sciatic nerve of the rat is electrically stimulated to
      induce fatigue in the medial Gastrocnemius muscle. Fatigue tests are carried out
      using intermittent stimulation of different compartments (sequential) or a single
      compartment (synchronous) of the sciatic nerve. The activation of different
      compartments is achieved by dividing nerve fibres into subbundles and placing
      them in separate grooves in a multigroove electrode. The aim of the investigation
      is to quantify the effect of sequential contra synchronised stimulation in
      reducing muscle fatigue, with no overlap between compartments. Overlap between
      two compartments is calculated using the combined and individual forces from both
      compartments. Sequential stimulation of two and three compartments is
      investigated. There is a significant decrease of fatigue in sequential
      stimulation compared to synchronous. After 2 min of intermittent stimulation the
      force time level is significantly increased in sequential stimulation, than in
      synchronous stimulation. The rate of force time decrease is significantly slower
      in sequential stimulation than in synchronous stimulation. With sequential
      stimulation it takes significantly longer before the maximal force time is
      reached than with synchronous stimulation.

PMID- 9246851
TI  - Pharyngeal wall vibration detection using an artificial neural network.
AB  - An artificial-neural-network-based detector of pharyngeal wall vibration (PWV) is
      presented. PWV signals the imminent occurrence of obstructive sleep apnoea (OSA)
      in adults who suffer from OSA syndrome. Automated detection of PWV is very
      important in enhancing continuous positive airway pressure (CPAP) therapy by
      allowing automatic adjustment of the applied airway pressure by a procedure
      called automatic positive airway pressure (APAP) therapy. A network with 15
      inputs, one output, and two hidden layers, each with two Adaline-nodes, is used
      as part of a PWV detection scheme. The network is initially trained using nasal
      mask pressure data from five positively diagnosed OSA patients. The performance
      of the ANN-based detector is evaluated using data from five different OSA
      patients. The results show that on the average it correctly detects the presence
      of PWV events at a rate of approximately 92% and correctly distinguishes normal
      breaths approximately 98% of the time. Further, the ANN-based detector accuracy
      is not affected by the pressure level required for therapy.

PMID- 9246852
TI  - Classification of normal and abnormal electrogastrograms using multilayer
      feedforward neural networks.
AB  - A neural network approach is proposed for the automated classification of the
      normal and abnormal EGG. Two learning algorithms, the quasi-Newton and the scaled
      conjugate gradient method for the multilayer feedforward neural networks (MFNN),
      are introduced and compared with the error backpropagation algorithm. The
      configurations of the MFNN are determined by experiment. The raw EGG data, its
      power spectral data, and its autoregressive moving average (ARMA) modelling
      parameters are used as the input to the MFNN and compared with each other. Three
      indexes (the percent correct, sum-squared error and complexity per iteration) are
      used to evaluate the performance of each learning algorithm. The results show
      that the scaled conjugate gradient algorithm performs best, in that it is robust
      and provides a super-linear convergence rate. The power spectral representation
      and the ARMA modelling parameters of the EGG are found to be better types of the
      input to the network for this specific application, both yielding a percent
      correctness of 95% on the test set. Although the results are focused on the
      classification of the EGG, this paper should provide useful information for the
      classification of other biomedical signals.

PMID- 9246853
TI  - New approach for elucidating the oxygen sensitivity and calibration of the
      antimony electrode.
AB  - The biomedical use of the polycrystalline antimony pH electrode is hampered by
      oxygen dependence and low pH resolution (0.1 pH). Although, the pH resolution is
      improved by using highly purified crystallographically oriented monocrystalline
      antimony (COMA), the oxygen effect on the electrode remains. In an in vitro
      examination of the COMA electrode it was found that the oxygen dependence is
      similar to that of polycrystalline antimony, i.e. nonlinear with an increase in
      sensitivity below 10 kPa. These findings imply that the oxygen tension in the
      vicinity of a COMA pH electrode, has to be known or controllable for the pH
      reading to be at all valid especially at low oxygen levels, such as is often seen
      in biomedical applications. A calibration procedure using a zero oxygen solution
      is used in order to obtain absolute pH readings in a measurement solution of pre
      set or known oxygen levels. Furthermore, the nonlinear oxygen sensitivity of the
      antimony electrode suggests that the underlying electrochemical reactions are
      other than those described by corrosion theory.

PMID- 9246854
TI  - Stimulus artefact in somatosensory evoked potential measurement.
AB  - When an electrical stimulus is used to evoke action potentials in peripheral
      nerves or the spinal cord, the stimulus causes an artefact which may interfere
      with measurement of the evoked potentials. This artefact, unlike all other
      sources of noise in the measurement, cannot be reduced by ensemble averaging.
      Confusion about the origin and transmission of stimulus artefact has led to
      considerable frustration in spinal somatosensory evoked potential (SSEP)
      measurements. The three mechanisms by which stimulus artefact is coupled into the
      measuring system are identified, and means for their reduction are discussed.

PMID- 9246855
TI  - Detection of fetal electrocardiogram signals using matched filters with adaptive
      normalisation.
AB  - The authors discuss the application of matched litters to the detection of R
      waves in fetal electrocardiogram (FECG) data, recorded during labour using a
      scalp electrode. When using the basic matched filter, one correlates a template
      representing the clean signal with the noisy signal. This method is optimal when
      the underlying noise is white in nature. However, it is known that false
      detection of R-waves can occur in the presence of extraneous peaks which have a
      similar shape to the fetal R-wave. It is proposed to switch between two different
      normalisations of the impulse response of the matched filter to alleviate this
      problem. When the signal-to-noise ratio is lower than a predetermined threshold,
      then normalisation to the geometric mean of the template and noisy data energies
      is carried out, otherwise only normalisation to the template energy is made. In
      the former case, the background noise and spikes that are larger than the
      underlying FECG are attenuated, hence increasing the probability of detection of
      the R-waves. In the latter case, noise, which has a lower amplitude than the
      underlying R-wave, is reduced. The effectiveness of this method is demonstrated
      by application to scalp electrode data.

PMID- 9246856
TI  - Understanding utero-placental blood flow in normal and hypertensive pregnancy
      through a mathematical model.
AB  - Normal development of utero-placental circulation is crucial not only for the
      survival and growth of the fetus in utero, but also for maternal well-being. Any
      disturbance or abnormality may reflect underlying pathology. Geometric conversion
      of a pre-pregnant spiral vessel into a divergent low-resistance vessel is
      believed to be responsible for the increased utero-placental blood flow in normal
      pregnancy. Known biomedical investigative techniques have failed to explain many
      such underlying haemodynamic changes taking place in the utero-placental system.
      Therefore, proper understanding of the system using a mathematical model has been
      found to be useful. The physiological fluid dynamic study is the first in this
      branch of physiology. Abnormal pressure gradient, axial velocity, volume flow and
      shear rate are obtained for various slowly changing geometries such as, tapering,
      divergence, local constrictions and sinusoidal tube for low Womersley parameters.
      The model can explain many enhanced patho-physiological changes, such as
      persistence or the appearance of local constriction in the utero-placental
      vessels. Such pathological changes are considered to be responsible for very high
      utero-placental resistance, leading to blood flow insufficiency in pre-eclampsia
      or intra-uterine growth retardations. It is believed that these changes may be
      caused by low shear rate on the pre-existing deranged or abnormal endothelium.
      Furthermore, this derangement is caused by an abnormal proliferation of either
      spiral vessels or the invading non-villous trophoblasts. Doppler flow study can
      explain and validate some of the theoretically derived flow velocity results. The
      study opens up a new area of research into utero-placental physiological fluid
      dynamics.

PMID- 9246857
TI  - Computer-based lung sound simulation.
AB  - An algorithm for the simulation of normal and pathological lung sounds is
      developed. The simulation algorithm is implemented on a personal computer as well
      as on a digital signal processor system in real time. Normal, bronchial and
      tracheal breathing sounds can be generated, and continuous and discontinuous
      adventitious lung sounds can be added. The attributes of the individual sound
      components, such as loudness, frequency, duration or number of occurrences within
      one breathing cycle, are controlled by the user. The quality of the simulations
      is evaluated by sending audio tapes to 15 experienced pulmonary physicians for a
      formal assessment. Each tape contains five simulated lung sounds and five real
      lung sounds from a commercially available teaching tape, presented in random
      order. Simulated lung sounds are slightly better rated in terms of realism and
      signal quality when compared to the recordings from the teaching tape. The
      differences are, however, not significant. 13 out of the 15 physicians feel that
      computer-based lung sound simulators would be a useful and desirable teaching
      tool for auscultation courses.

PMID- 9246858
TI  - Matching of digitised brain atlas to magnetic resonance images.
AB  - A method has been developed to match a standard digitised brain atlas onto MR
      images for identification of cerebral structures in anatomical images. This
      method uses, first, a three-dimensional crude registration based on the
      proportional system of Talairach. Then, a two-dimensional refined registration is
      performed using a deformation function based on a set of homologous landmarks on
      both images (MR and atlas). Displacements vectors are computed between each
      corresponding landmark. These vectors are interpolated by thin-plate splines,
      generating an unwarping function defined on the whole image. This function can
      then be applied on any structure of the atlas. An evaluation of the matching
      procedure has been performed. First, the influence of the choice of the landmarks
      has been evaluated for the fine registration method. The latter has been then
      compared to the crude registration method considered as a classical reference
      method. These results show the advantages of the fine registration approach.

PMID- 9246859
TI  - Characterisation of structural changes in the arterial elastic matrix by a new
      fractal feature: directional fractal curve.
AB  - A new fractal feature, the Directional Fractal Curve (DFC), defined over an arc
      of 180 and composed of 90 fractal dimensions determined at intervals of arc of 2,
      is developed to account for the anisotropic property of a fractal texture. The
      DFC algorithm is first applied to two images with different textural patterns,
      one without directional preference and one with a well-organised texture. The DFC
      of these images shows different patterns. The technique is then applied to
      quantify the structure of the elastic texture in the arterial wall where the
      elastic network was imaged by scanning electron microscopy following selective
      tissue digestion. The results suggest: (i) that images of the elastin matrix of
      the arterial wall exhibit fractal properties with directional preference, (ii)
      the DFC gives quantitative parameters which allow characterisation of structural
      changes in the elastin matrix of the arterial wall in terms of disorganisation
      and fragmentation of elastin fibres-conditions which are associated with medial
      degeneration due to normal ageing or presence of arterial disease.

PMID- 9246860
TI  - Laser reflectance imaging of human organs and comparison with perfusion images.
AB  - Based on the principle of backscattering of laser radiation from tissues, a non
      invasive PC-AT based reflectance imaging technique is developed. The laser beam
      from a semiconductor laser operating at 670 nm is guided to the tissue site by an
      optical fibre. The backscattered radiation is collected by another fibre placed
      in the same probe, and is detected by a photodiode-amplifier assembly. This probe
      is moved manually over the organs under observation, and the data after the ADC,
      interpolation and median filtering are displayed in the form of reflectance image
      of the organ along with grey scale. By this technique images of the human hands
      and forearms are obtained, which depend on the variations in their colour,
      composition and blood flow. A comparison is made with perfusion images, obtained
      by a Periflux laser Doppler flowmeter. These show that the reflectance images
      provide greater details of the tissue structure than the perfusion images.

PMID- 9246861
TI  - Information in magnetic resonance images: evaluation of signal, noise and
      contrast.
AB  - The assessment of diagnostic image quality for MRI is considered. The assessment
      of three key image quality determinants is addressed: signal, noise and contrast.
      There is a distinction between random noise evaluation, for the calculation of
      the SNR, and structured noise evaluation for the assessment of image artefacts.
      Specific methods used are correlation techniques and the Wiener spectrum.
      Contrast is assessed by comparison of experimental data and theoretical
      predictions. For each assessment, the theory and method of the evaluation
      strategy are discussed. The discussion is illustrated with analysis results from
      commercial MR systems. The choice of analysis method and the subsequent
      derivation of quality indices are shown to be critical in respect of robustness
      and accuracy.

PMID- 9246862
TI  - Extra- and intracellular volume monitoring by impedance during haemodialysis
      using Cole-Cole extrapolation.
AB  - A method is presented for monitoring the relative variation of extracellular and
      intracellular fluid volumes using a multifrequency impedance meter and the Cole
      Cole extrapolation technique. It is found that this extrapolation is necessary to
      obtain reliable data for the resistance of the intracellular fluid. The
      extracellular and intracellular resistances can be approached using frequencies
      of, respectively, 5 kHz and 1000 kHz, but the use of 100 kHz leads to
      unacceptable errors. In the conventional treatment the overall relative variation
      of intracellular resistance is found to be relatively small.

PMID- 9246863
TI  - Theoretical analysis of non-invasive oscillometric maximum amplitude algorithm
      for estimating mean blood pressure.
AB  - A theoretical analysis is performed to evaluate the effect of arterial mechanical
      and blood pressure pulse properties on the accuracy of non-invasive oscillometric
      maximum amplitude algorithm (MAA) estimates of the mean blood pressure obtained
      using air-filled occlusive cuffs. Invasively recorded blood pressure pulses,
      selected for their varied shapes, are scaled to simulate a wide range of blood
      pulse pressures (diastolic blood pressure minus systolic blood pressure). Each
      scaled blood pressure pulse is transformed through an exponential model of an
      artery to create a series of blood volume pulses from which a simulated
      oscillometric waveform is created and the corresponding MAA estimate of the mean
      blood pressure and error (mean blood pressure minus MAA estimate) are determined.
      The MAA estimates are found to depend on the arterial blood pressure. The errors
      are found to depend on the arterial mechanical properties, blood pressure pulse
      shape and blood pulse pressure. These results suggest that there is no direct
      relationship between the mean blood pressure and MAA estimate, and that multiple
      variables may affect the accuracy of MAA estimates of the mean blood pressure
      obtained using air-filled occlusive cuffs.

PMID- 9246864
TI  - High-pass filtering of the electrogastrogram.
AB  - The recording and processing of an electrogastrogram require adequate band-pass
      filtering, to suppress unwanted artefacts but preserve the original signal
      waveform. High-pass filtering of various types, of different time constants tau,
      filter order, analogue and digital implementation, have been used to obtain
      higher baseline stability and faster signal recovery after strong artefacts.
      Special attention should be given to possible signal amplitude and phase
      distortions due to high-pass filtering, which can strongly influence accurate
      amplitude measurements or studies of signal propagation from multichannel
      recordings. Synthesised and original signals are used to demonstrate the effect
      of high-pass filtering. The use of a first-order filter with tau = 5 s is
      recommended for EGG studies if not especially directed to investigation of
      bradygastria. In the opposite case, tau = 15 s should be used, and with backward
      filtering a full restoration of the original signal can be obtained. The same is
      valid for recording the electrical activity of the colon. Lower time constants
      (tau = 5 s or less) can be applied to acquire signals from the small intestines.
      A radical solution is the use of a DC amplifier with controllable subtraction of
      the DC component.

PMID- 9246866
TI  - On refraction in Monte-Carlo simulations of light transport through biological
      tissues.
AB  - To obtain reliable results from Monte-Carlo simulations of light scattering
      experiments, a statistically accurate procedure for positioning the photons after
      refraction between two different scattering media is necessary. Two statistically
      equivalent algorithms for calculating the position of the photons immediately
      after crossing an interface are described and justified.

PMID- 9246865
TI  - Aspects of silicone rubber as encapsulant for neurological prostheses. Part 4:
      Two-part rubbers.
AB  - The durability of the adhesion, in the presence of water, of three two-part
      silicone rubbers to five adherends of practical interest is examined. The results
      are contrasted with those obtained, in previous work, from single-part material.
      It is concluded that two-part rubbers promise outstanding performance in
      particular circumstances.

PMID- 9246867
TI  - Force measurement on fracture site with external fixation.
AB  - A force measurement device has been designed to monitor the mechanical properties
      of fracture site with external fixation. Forces are measured through electric
      resistance strain gauges mounted on fixation framework and the measurement
      results are displayed on an LCD screen. The device features a force range of 0-10
      kg with linearity and repeatability less than 1% and accuracy less than 0.1 kg.

PMID- 9246868
TI  - Computer-based anthropometrical system for total body irradiation.
AB  - For total body irradiation (TBI) dose calculation requirements, anatomical
      information about the whole body is needed. Despite the fact that video image
      grabbing techniques are used by some treatment planning systems for standard
      radiotherapy, there are no such systems designed to generate anatomical
      parameters for TBI planning. The paper describes an anthropometrical computerised
      system based on video image grabbing which was purpose-built to provide
      anatomical data for a PC-based TBI planning system. Using software, the system
      controls the acquisition and digitalisation of the images (external images of the
      patient in treatment position) and the measurement procedure itself (on the
      external images or the digital CT information). An ASCII file, readable by the
      TBI planning system, is generated to store the required parameters of the dose
      calculation points, i.e. depth, backscatter tissue thickness, thickness of
      inhomogeneity, off-axis distance (OAD) and source to skin distance (SSD).

PMID- 9246870
TI  - Adaptive autoregressive modeling used for single-trial EEG classification.
AB  - An adaptive autoregressive (AAR) model is used for analyzing event-related EEG
      changes. Such an AAR model is applied to single EEG trials of three subjects,
      recorded over both sensorimotor areas during imagination of left and right hand
      movements. It is found that discrimination between both types of motor-imagery is
      possible using linear discriminant analysis, but the time point for optimal
      classification is different in each subject. For the estimation of the AAR
      parameters, the Least-mean-squares and the Recursive-least-squares algorithms are
      compared. In both methods, the update coefficient plays a key role: it determines
      the adaptation ratio as well as the estimation accuracy. A new method, based on
      minimizing the prediction error, is introduced for determining the update
      coefficient.

PMID- 9246869
TI  - An experimental high energy therapeutic ultrasound equipment: design and
      characterisation.
AB  - High energy ultrasound equipment for well controlled experimental work on
      extracorporeal shockwave lithotripsy (ESWL) and hyperthermia has been built. The
      design of two sets of equipment with operating frequencies of 0.5 and 1.6 MHz,
      respectively, is described and characterised in terms of measured generated
      pressure fields. The treatment heads consist of six or seven focused ultrasound
      transducers. The transducers have a diameter of 50 mm each and are mounted in a
      hemispherical Plexiglass fixture with a geometrical focus 100 mm from the
      transducer surfaces. Measurements were performed in a water bath in several
      planes perpendicular to the central axis of the ultrasound beam, using a
      miniature hydrophone which was positioned with a computer controlled stepping
      motor system. Resulting diagram plots show well defined pressure foci, located at
      the geometrical foci of the transducer units.

PMID- 9246871
TI  - [Extensive rehabilitation needed in epilepsy. Different models for varying
      needs].
AB  - Many people with epilepsy experience the need for more information concerning
      their condition and some people require, at times, greater access to
      rehabilitation services than has previously been available. Information and
      support may also be required by the family, friends and work colleagues of the
      patient. Research indicates that rehabilitation needs, for the patient, can arise
      in relation to poor self-esteem, overprotection as a child, low expectations,
      reduced cognitive abilities and stigma perceived or experienced in the family, in
      society, and at work. Successful rehabilitation is individualistic and should
      therefore be based on an assessment of the individual's needs. Only on the basis
      of this can realistic goals be identified. In the cases where intensive
      multidisciplinary rehabilitation is required a thorough medical assessment will
      also be needed in order to formulate realistic goals. Achievement of these goals
      may involve input from psychological, neuropsychological, pedagogical, social,
      employment and family orientated perspectives. Specialists in these areas must be
      included within, or co-ordinated by, the epilepsy team or rehabilitation service.
      In Sweden hospital based epilepsy-teams have added psycho-social rehabilitation
      aspects in their responsibilities and other rehabilitation services have recently
      begun to focus on the needs of people with epilepsy. This has led to a range of
      different rehabilitation models being available. The need to develop improved
      epilepsy rehabilitation services was identified in the 1970s and has recently
      received short-term funding support to develop new services and build up
      expertise. It is hoped that in the future these services will continue to find
      support at both the county and national levels.

PMID- 9246872
TI  - [The Madrid declaration. New ethical guidelines in psychiatry].

PMID- 9246873
TI  - Poststroke anxiety and its relationship to coping and stage of recovery.
AB  - Anxiety disorders are reported to be common but poorly understood poststroke
      phenomena. The relationships between symptoms of anxiety, coping activity, and
      stage of recovery were investigated in 44 subjects who had suffered strokes (mean
      age 68.6 years). Consistent with general models of anxiety disorders, anxiety was
      associated with more frequent use of avoidant coping strategies. No significant
      relationship was found between time poststroke and self-reported distress.

PMID- 9246874
TI  - Social psychological indicators associated with the suicide rate: a comment.

PMID- 9246875
TI  - Relations of perceived causes and the experience of loneliness.
AB  - Previous research yielded five factors which comprise the experience of
      loneliness, namely, Emotional distress, Social inadequacy and alienation, Growth
      and discovery. Interpersonal isolation, and Self-alienation. The perceived causes
      of loneliness were grouped into factors of Personal inadequacies, Developmental
      deficits, Unfulfilling intimate relationships, Relocation and significant
      separations, and Social marginality. Using principal components factor analysis,
      the relations of perceived causes and the various aspects of loneliness were
      examined for 295 men and 338 women. All five of the perceived causes appeared to
      contribute to experienced loneliness. While scores on Emotional distress were
      strongly related to all five factors of perceived causes, the other four factors
      were differentially related.

PMID- 9246876
TI  - Adolescent inpatients' history of abuse and dissociative identity disorder.

PMID- 9246877
TI  - MMPI and MMPI-2 scores on the Cook-Medley Hostility Scale.
AB  - Raw-score means of the Cook-Medley Hostility scale are smaller in the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2) normative group than in the MMPI
      normative group, and T scores are larger. The results contrast with those for the
      clinical scales but are consistent with results for some other scales. Reasons
      for the different patterns of MMPI and MMPI-2 scores are discussed.

PMID- 9246879
TI  - Nonverbal intellectual assessment of Hispanic and speech-impaired adolescents.
AB  - A comprehensive new nonverbal cognitive battery (Leiter-R) was given to examine
      the nonverbal cognitive performance of adolescents, ages 11 to 21 from majority
      and nonmajority (Hispanic) ethnic backgrounds. A total of 258 Euro-American (non
      Hispanic) and 62 Hispanic adolescents composed the ethnic-contrast samples (81%
      Euro-American vs 19% Hispanic). Also, the study used the Leiter-R to contrast the
      cognitive performance of speech-impaired adolescents with typical children, ages
      11 to 15. There were 203 without and 21 with speech impairments. The speech
      impaired contrast sample was comprised of Euro-American (75%) and African
      American (25%). This sampling provided direct comparisons equated for ethnicity.
      Small effect size differences (.11) were found on 3 of the 10 nonverbal subtests
      of the Visualization and Reasoning battery of the Leiter-R between Euro-American
      and Hispanic adolescents and the speech-impaired contrasts (effect size
      difference of .17). The Leiter-R exhibited potential for ethnic fairness in
      assessment. Further, promise for unbiased assessment of speech-impaired
      adolescents was provided. Fairness of assessment was especially evident for
      speech-impaired adolescents on the "visual" subtests of Picture Context,
      Matching, and Form Completion.

PMID- 9246878
TI  - Assessing stress among public school principals in British Columbia.
AB  - 643 public school principals in British Columbia, Canada responded to a survey on
      administrative stress. The findings show that stress is a serious concern for
      these administrators. In contrast to other studies of administrative stress,
      "administering the negotiated contract" was a source of stress uniquely important
      to school principals in British Columbia. A multivariate analysis indicated that
      principals who had greater total scores on the measure of administrative stress
      perceived that administrative isolation was a problem for them, reported greater
      stress due to the job, had seriously considered leaving school administration,
      felt that principals were under greater stress than other members of their
      community and reported that they had to cope with scarce or limited resources at
      their schools.

PMID- 9246881
TI  - Effects of alcohol on responsive laughter and amusement.
AB  - After consuming either an alcoholic or nonalcoholic beverage, 48 subjects viewed
      a humorous film. Frequency of responsive laughter and subjective amusement was
      significantly greater in the alcohol group.

PMID- 9246880
TI  - Political identification and perceptions of homelessness: attributed causality
      and attitudes on public policy.
AB  - The study investigated relationships between political orientation, causal
      perceptions of poverty, and attitudes toward government programs for the poor.
      The test sample of 200 women and 200 men were recruited from introductory
      psychology classes. In support of hypotheses based on previous research and
      Weiner's attribution-emotion-action theory, when compared with self-identified
      Democrats, self-identified Republicans (a) were significantly more inclined to
      attribute homelessness to internal vs external factors and (b) expressed
      significantly less favorable attitudes toward publically funded programs for the
      homeless. Sex differences were nonsignificant. Conceptual-empirical and
      methodological implications are discussed. Limitations on inferences from these
      data and directions for inquiry into the development of individual difference in
      political cognitions and public policy attitudes are considered.

PMID- 9246882
TI  - Attribution of responsibility for alcohol-related offenses.
AB  - The present study examined how individuals attribute responsibility for alcohol
      related offenses. Subjects were classified into 4 groups based on the type of
      consequences they received for their alcohol use and were asked to complete 2
      measures of causal attributions following each of 2 scenarios which depicted
      different severities of outcome of alcohol-related offenses. Using a 2-way
      multiple analysis of variance the 2 x 4 repeated-measures design indicated no
      significant difference between groups based on consequences. A significant
      difference was found for severity of outcome suggesting individuals attribute
      differing responsibility based on the outcome of alcohol-related events.

PMID- 9246883
TI  - Managing students with behavior disorders: perceived efficacy of interventions.
AB  - This study examined the perceived efficacy of interventions commonly used by
      teachers of students with behavior disorders. Of 30 interventions used with
      approximately 1200 students labeled behaviorally disordered, 149 teachers ranked
      22 as effective, and 8 were more often ranked as seldom effective. These findings
      have implications for teachers' preparation and identifying better practices for
      teaching students with behavior disorders.

PMID- 9246884
TI  - Adjustment of children and interaction of parent and child among single mothers
      in a disadvantaged South African community.
AB  - This study investigated the relationships among family status (intact vs single
      parent), socioeconomic status, parent-child interaction, and children's
      adjustment in a disadvantaged "Coloured" community in South Africa. Data were
      collected from 48 mothers, including 12 married mothers of higher socioeconomic
      status, 12 single mothers of higher socioeconomic status, 12 married mothers of
      low socioeconomic status, and 12 single mothers of low socioeconomic status. Low
      socioeconomic status, single mothers rated their children as significantly less
      adjusted than mothers in the other three groups. These and other findings suggest
      the importance of taking both family status and socioeconomic status into
      account. While the findings of this study are not conclusive, they could have
      implications for the "Coloured" community of South Africa and similar groups.

PMID- 9246885
TI  - Acculturation and MMPI-2 scale scores of Mexican American substance abuse
      patients.

PMID- 9246886
TI  - Life satisfaction and the five-factor model of personality.
AB  - The hypothesis that happy and unhappy people have different personality profiles
      based on five personality factors (Neuroticism, Extraversion, Openness,
      Agreeableness, and Conscientiousness) was tested using 245 undergraduates (111
      men and 134 women) who completed the Satisfaction with Life Scale and the NEO
      Personality Inventory. Analysis indicated that High and Low Satisfaction groups
      had significantly different personality profiles, supporting the hypothesis.

PMID- 9246887
TI  - Major depression: a breakdown in sense of coherence?
AB  - The relationship between major depression and the salutogenic construct of sense
      of coherence was investigated. The Sense of Coherence scale and the Beck
      Depression Inventory were administered to 50 patients diagnosed with major
      depressive disorder and to 50 control subjects. Significant negative correlations
      were found between scores on Depression and total scores on the Sense of
      Coherence scale as well as all three of its subscales (Comprehensibility,
      Manageability, and Meaningfulness). A significant positive correlation was found
      between scores on the Sense of Coherence scale and age. Of the three subscales, a
      low score on Meaningfulness was the best predictor of scores on Depression.

PMID- 9246888
TI  - Self-reported locus of control is based on feelings of depression as well as on
      asymmetry in activation of cerebral hemispheres.
AB  - In a sample of 50 patients with primary breast cancer we obtained interviews,
      answers to questionnaires, blood samples, and reaction times on two stimulus
      discrimination tests on the day of admission to the hospital for a biopsy. Locus
      of control scores on Rotter's I-E Locus of Control Scale seemed to be directly
      associated with an indicator of depressed mood and one of relative activation of
      the right cerebral hemisphere. Other variables of which one might have expected a
      mediating role did not show significant partial relationships with the dependent
      variable.

PMID- 9246890
TI  - "Indirect" suggestion in hypnosis: theoretical and experimental issues.
AB  - "Indirect" suggestion is conceptualized in two distinct ways in the literature.
      From an Ericksonian perspective "indirect" suggestions are theoretically
      approached as suggestions which can circumvent the censorship of consciousness to
      reach the "unconscious" where they can activate dormant potentials. In contrast,
      from a research perspective "indirect" suggestion is operationally defined as a
      technique. Based on Ericksonian theory, it was claimed that "indirect" suggestion
      was more effective than traditional, "direct" suggestion. However, this claim
      could not be empirically substantiated. In this paper it is shown that the
      theoretical claim is based on questionable assumptions about the existence of the
      "unconscious" as a reified entity and about the direct and lineal influence of
      certain suggestions on this entity. Also, it is argued that traditional research
      strategies which emphasize strict controls are unable to verify or unambiguously
      refute the Ericksonian claim because these strategies are biased toward "direct"
      suggestion. Finally, the paper provides a different, contextual perspective on
      "indirect" suggestion, thereby placing the theoretical and experimental issues in
      a different context of meaning.

PMID- 9246891
TI  - Symptom patterns in schizophrenia for men and women.
AB  - Differences on symptoms and anamnestic variables were studied in a sample of 112
      Canadian patients (42 men and 70 women) who met DSM-III criteria for
      schizophrenia. Men were more often rated as providing unreliable information than
      were women. A smaller proportion of men than women showed spontaneous remissions
      (a return to premorbid level), and fewer men also displayed phasic changes in
      appetite, weight, or sexual activity. It is noteworthy that men and women did not
      differ on general indices of severity of illness such as the number of past
      hospitalizations or length of hospital stay. In contrast to numerous past
      studies, an earlier age of onset of the illness for men was nonsignificant.

PMID- 9246889
TI  - Young adults' drug use: a 17-year longitudinal inquiry of antecedents.
AB  - This longitudinal study examined the interrelation of personality and peer
      factors on young adults' drug use and also the influence of the interaction of
      personality and peer factors on drug use. The sample of 756 males and females
      were interviewed four times between the M ages of 6 and 22. Personality
      attributes in childhood were related to peer factors in early adolescence which,
      in turn, were related to personality traits in later adolescence. These traits
      were linked with selection of peers and, ultimately, drug use in young adulthood.
      Additionally, the adolescent and young adult domains had direct effects on young
      adults' drug use. Significant interactions indicated that a few protective
      childhood personality traits buffer the risk of deviant peers in adolescence on
      young adults' drug use. More earlier protective characteristics from one domain
      enhanced the effect of later protective traits from the other domain.

PMID- 9246892
TI  - Changes in women's emotions as a function of emotion valence, self-determined
      category of premenstrual distress, and day in the menstrual cycle.
AB  - A confirmatory study where 20 women completed Plutchik and Kellerman's Emotions
      Profile Index in a daily prospective rating of emotions supported previous
      findings of mood fluctuations across the menstrual cycle. Positive moods peaked
      at or about the time of ovulation and negative ones at or about the time of
      menstruation. However, significant interactions indicated that a pronounced shift
      in mood was only characteristic of women who rated themselves as "sufferers" of
      premenstrual discomfort and not of those who rated themselves as experiencing
      very mild discomfort.

PMID- 9246893
TI  - Locus of control, depression and suicidality in Korean workers.

PMID- 9246894
TI  - Sex differences in suicide notes.

PMID- 9246895
TI  - Research on homeless men and women: existential-humanistic and clinical thinking.
AB  - Researchers interested in homeless persons have concentrated on disease,
      overlooking assets. The content of this paper challenges researchers to a more
      comprehensive view of homeless samples to include mental wellness.
      Recommendations for research are suggested.

PMID- 9246896
TI  - The relation between states' adoption of English as their official language to
      demographic and social pathology variables.
AB  - Comparisons indicated that the 20 states which adopted English as their official
      language since 1984 had lower percentages of high school graduates and higher
      rates of motor vehicle fatalities among their residents than did those states
      that did not enact such laws. The two types of states did not differ in homicide,
      suicide, divorce, illegitimacy, or rape rates based on 1990 census data. Also,
      they did not differ in terms of percentages of residents who were foreign-born,
      college graduates, imprisoned, unemployed, or who spoke a language other than
      English in the home.

PMID- 9246897
TI  - Psychopathology in obese subjects with and without binge-eating disorder and in
      bulimic subjects.
AB  - The present study was conducted with three groups of 15 subjects each, obese
      subjects diagnosed with Binge Eating Disorder, obese subjects without diagnosis
      of Binge Eating Disorder, and bulimic subjects. The aim was to compare the three
      groups on a battery of self-administered tests for psychodiagnostic screening.
      Analysis showed a clear pattern: patients with bulimia nervosa had higher
      pathological scores in the specific area of eating disorders than did obese
      patients, whereas patients with Binge Eating Disorder tended to score lower than
      patients with bulimia nervosa and higher than did the obese patients. This
      general pattern is very similar to the findings recently reported in the
      literature and suggests the adoption of a clinical approach which takes into
      account the different characteristics of the three groups.

PMID- 9246898
TI  - Perceptual differences in racial descriptions of Euro-American and Hispanic
      persons.
AB  - This study examined negative stereotypes held about Hispanic persons by 116 Euro
      American graduating MBA students. Schein's 92-item Descriptive Questionnaire
      (1973) was rated by subjects as either positive (e.g., intelligent, persistent,
      ambitious, etc.) or negative (e.g., uncertain, passive, nervous, etc.). 53 items
      were characterized as positive while 18 were considered negative. When applied to
      Euro-American and Hispanic persons, zero and 8 negative items, respectively,
      could be used to describe these two groups in general. Conversely, while 26
      positive items were used exclusively to describe Euro-American persons, only one
      could be applied exclusively to Hispanic persons. The potential effects of such
      perceptions on Hispanic persons job opportunities are discussed.

PMID- 9246899
TI  - Hypochondria in women as a function of birth order.
AB  - The hypothesis that firstborn women would score higher than later-born women on a
      measure of hypochondria was supported. This result is explained in terms of
      parental treatment, specifically, the modeling of greater concern about the
      health of their girls by inexperienced parents.

PMID- 9246900
TI  - Self-reported sexual behaviors of high school juniors and seniors in North
      Dakota.
AB  - The period of adolescence is characterized as a time of experimentation during
      which adolescents may engage in adult behavior in the absence of understanding
      the consequences of these behaviors. The purpose of this study was to examine the
      self-reported sexual behaviors of late adolescent junior and senior high school
      students (N = 7,699). The study indicated a significantly high and disconcerting
      frequency of self-reported risk-taking sexual behavior.

PMID- 9246901
TI  - Development of the eating Attitude Inventory for Diabetes Mellitus.
AB  - The authors examined the validity and reliability of the Eating Attitude
      Inventory for Diabetes Mellitus in a sample of 178 patients with diabetes
      mellitus. Reliability was supported by factor analysis, adequate internal
      consistency, and relatively high test-retest correlations. Validity was indicated
      by correlation with the Eating Attitudes Test designed for eating disorders. This
      inventory may be useful for assessing eating attitudes of patients with diabetes
      mellitus.

PMID- 9246902
TI  - The Kogan Attitudes Toward Old People scale: is it time for a revision?
AB  - The Kogan Attitudes Toward Old People scale scale has been used in gerontological
      research for more than 35 years. Criticisms of the scale, including dated wording
      and response bias, have increased in the 1990s. Researchers must examine the
      scale and decide whether a revision is now necessary.

PMID- 9246903
TI  - Relationship of mothers' perceptions and behaviors to the duration of
      breastfeeding.
AB  - The relationship between duration of breastfeeding in the first 12 weeks after
      birth, characteristics of mothers' and infants' behaviors, and the mother's
      perception of her infant were studied in primiparous mothers and their low-risk
      newborn infants. 50 women completed questionnaires on infants' temperament,
      caregiving flexibility, and perception of breastfeeding in their third trimester
      of pregnancy and again when their infants were 12 weeks old. 30 of the 50 women
      and their infants were observed for two hours on each of three different
      occasions at their homes when infants were 2, 6, and 12 wk. of age. Higher rates
      of mothers' interactive behaviors with their infants, mothers' self-reported
      perceptions that their infants had "easy" temperaments, and mothers' self
      reported flexibility of caregiving were directly correlated with longer duration
      of breastfeeding and later weaning from the breast.

PMID- 9246904
TI  - Stress factors in the aftermath of Hurricanes Erin and Opal: data from small
      business owners.
AB  - Hurricanes Erin and Opal struck the same coastal region in the Northwest Florida
      Panhandle in late summer of 1995. The study examined the stressors that most
      affected small businesses in the region in the aftermath of the storms. Power
      outages, telephone disruptions, employees' availability, debris removal, and lack
      of customers were the major problem areas reported by business owners (N = 57 of
      500 potential respondents). The results indicate that most of the stress factors
      were transitory and the findings are discussed in light of Murphy's 1985
      conceptual model of disaster research.

PMID- 9246905
TI  - Toward a system theory of the mind.

PMID- 9246906
TI  - Preimplantation genetic diagnosis of inherited disease.
AB  - Research on diagnosis of inherited disease in human embryo before implantation
      was initiated to help those couples who would prefer to select embryos at this
      stage rather than during pregnancy. Following in vitro fertilization (IVF), one
      to two cells were removed from 3 day cleavage stage embryo and cells were
      analysed for genetic defects. Embryos diagnosed as unaffected were returned to
      the uterus and thus the resulting pregnancies were assured to be normal. First
      babies born after the preimplantation diagnosis were using DNA amplification of Y
      linked sequences by PCR to avoid X-linked disease. Several pregnancies were
      obtained by identifying sex of embryos using dual fluorescent in situ
      hybridization (FISH) with fluorochrome labelled DNA sequences specific for X- and
      Y-chromosomes to interphase nuclei. Development of single cell PCR for single
      gene defects led to diagnose several genetic disorders. Preimplantation diagnosis
      was successfully achieved for predominant delta 508 deletion causing cystic
      fibrosis, and pregnancies were also diagnosed for Lesch-Nyhan syndrome, Tay-Sachs
      and Duchenne muscular dystrophy.

PMID- 9246908
TI  - Effects of some anxiogenic agents on rat brain monoamine oxidase (MAO) A and B
      inhibitory (tribulin) activity.
AB  - Anxiogenic agents, yohimbine, pentylenetetrazole (PTZ), quinine, bufotenine,
      flumazenil and isatin were administered (ip) to rats at doses known to induce
      anxiety in this species. All the drugs exhibited anxiogenic response on the
      elevated plus-maze and induced a parallel increase in endogenous brain monoamine
      oxidase (MAO) inhibitory (tribulin) activity. The intensity of the drug-induced
      anxiety was fairly well correlated with the magnitude of increase in the MAO A
      inhibitory component of tribulin but not so with its MAO B inhibitory component.
      Thus, in the doses used, the degree of anxiogenic activity was PTZ > yohimbine >
      bufotenine > quinine > isatin > flumazenil, in terms of % entries on the open
      arms of the maze, whereas the magnitude of endogenous MAO A inhibition was PTZ >
      yohimbine > bufotenine > quinine > flumazenil > isatin. The results indicate that
      the MAO A inhibitory component of tribulin, rather than its MAO B inhibitory
      component, may be responsible for the postulated function of tribulin as an
      endogenous marker of anxiety.

PMID- 9246907
TI  - Hyperthermia in cancer research: current status.
AB  - There are critical maximum temperatures above which irreversible damage occurs in
      cells and tissues. Exposure to high temperature, referred to as hyperthermia
      (HT), can result in cell death, tissue damage or even death of the organism.
      Clinical application of HT as a primary treatment or as an adjuvant to radio
      /chemo- therapy of cancer is based on its ability to cause localized tumor tissue
      damage. Experimental data provide HT with a strong biological rationale. Early
      clinical experience suggested that HT will become an important modality as an
      adjuvant to radiotherapy in the treatment of human malignancies, but its
      application is currently limited to mainly superficial tumors. Its full
      realization as a treatment modality for cancer therapy awaits further laboratory
      investigations as well as controlled clinical trials. A better understanding of
      the biological mechanisms of its action, interaction with chemotherapeutic drugs
      and radiation damage, role of tumor microenvironment such as oxygen status and pH
      of tumors, and kinetics of thermotolerance can lead to refinement in its clinical
      implementation. The present review attempts to analyse the published literature
      during the last one and half decades.

PMID- 9246909
TI  - Radioprotective effects of diltiazem on cytogenetic damage and survival in gamma
      ray exposed mice.
AB  - Diltiazem, a calcium ion channel blocker, already in use in cardiovascular
      therapeutics, has been observed to protect against bone marrow damage
      (cytogenetic damage, cell death) and mortality in whole body irradiated mice. The
      micronuclei fraction in bone marrow cells of whole body irradiated (60Co gamma
      rays, 2.0 Gy) mice was reduced from 2.24 +/- 0.23% to about 0.74 +/- 0.33% by
      preirradiation administration (-20 min) of 110 mg/kg body wt. diltiazem (ip).
      Endogenous colony forming unit counts in spleen of mice administered 110 mg/kg
      body wt. (-20 min) of diltiazem before 10 Gy whole body irradiation were 6 times
      more than untreated irradiated controls. Pretreatment with diltiazem accelerated
      the recovery of radiation induced weight loss also. Diltiazem (110 mg/kg body wt,
      -20 min) enhanced 30 day survival to about 95% and 85% after lethal whole body
      absorbed dose of 9 and 10 Gy respectively and also mitigated radiation induced
      life- span shortening. Post-irradiation (10 Gy) administration of diltiazem (+20
      to 30 min) enhanced survival from about 2 to 15% only but was highly significant
      (P < 0.001). Possible modes of radioprotective action of diltiazem have been
      discussed.

PMID- 9246910
TI  - Effect of petroleum ether extract from Hygrophila spinosa on hematological
      parameters and hepatorenal functions in mice.
AB  - Multiple doses of H. spinosa were administered, ip once in a week for 4 weeks
      (20, 40 and 80 mg/kg body weight) and daily for one month (2, 4 and 8 mg/kg body
      weight). No alteration in biochemical parameters at low and moderate dose level
      of daily and low dose level of weekly treatment of petroleum ether extract was
      observed. However, the extract at moderate dose level in weekly treatment changed
      serum aminotransferase, alkaline phosphatase and plasma cholesterol
      significantly. High dose level of the extract changed all the above parameters of
      weekly treated mice including total bilirubin, nonprotein nitrogen, blood urea
      and plasma protein. High dose level of daily treatment and moderate and high dose
      level of weekly treatment of the root extract increased only the white blood cell
      count significantly. The results reveal that the weekly moderate and high dose
      (above 40 mg/kg body weight) and daily/therapeutic high dose (8 mg/kg) of the
      petroleum ether extract of H. spinosa affects liver and kidney functions and
      metabolism and hematological parameters whereas low weekly dose (20 mg/kg) and
      low and moderate daily/therapeutic dose (2 and 4 mg/kg) does not exhibit any
      appreciable toxic action.

PMID- 9246911
TI  - Pharmacological actions of Pongamia pinnata seeds--a preliminary study.
AB  - Direct ethanolic and sequential petroleum ether, chloroform, acetone and
      ethanolic extracts (50-100 mg/kg, i.p.) of P. pinnata seeds given 30-60 min
      before revealed anti-inflammatory, analgesic and anti-ulcerogenic activities in
      rats. The activities were present maximum in petroleum ether and chloroform
      extracts. However, the extracts also showed shortening of pentobarbitone induced
      'sleep time' in rats.

PMID- 9246914
TI  - Behavioural effects of prenatal and postnatal undernutrition in rats.
AB  - Effects of pre- and post-natal undernutrition on anxiety and depression paradigms
      were studied in albino rats. Prenatal undernutrition was induced in rat pups by
      restricting the dam's daily food during the gestation period whereas postnatal
      undernutrition in rat pups was induced by rotating them between lactating and non
      lactating maternalised females daily for 12 hr during suckling period from 2nd to
      18th day after birth. At 2.5 to 3 months of age all the rat pups were subjected
      to (i) elevated plus maze behaviour, (ii) open-field behaviour, and (iii)
      swimming induced behavioural despair tests. The results indicate that postnatal
      undernutrition caused significantly increased anxiety in the elevated plus maze
      as well as in open-field behaviour tests. Whereas prenatal undernourishment
      caused lesser degree of anxiogenic behaviours in the elevated plus maze test.
      Prenatally undernourished rats showed increased anxiety in the open-field
      behaviour test. Both, pre- and post-natal undernutrition also lead to increased
      depressive behaviour in the behavioural despair test and postnatal
      undernourishment caused greater degree of behavioural despair.

PMID- 9246913
TI  - Chemical and pharmacological studies on fixed oil of Ocimum sanctum.
AB  - Gas liquid chromatographic analysis of fixed oil of O. sanctum revealed the
      presence of five fatty acids (stearic, palmitic, oleic, linoleic and linolenic
      acids). The triglyceride fraction of the oil showed higher protection compared to
      fixed oil against carrageenam-induced paw edema and acetic acid-induced writhings
      in rats and mice, respectively. The pharmacological activity of the fixed oil
      could be attributed to its triglyceride fraction or the fatty acids.

PMID- 9246912
TI  - Effects of Centella asiatica extract on dermal wound healing in rats.
AB  - Effects of oral and topical administration of an alcoholic extract of C. asiatica
      on rat dermal wound healing was studied. The extract increased cellular
      proliferation and collagen synthesis at the wound site, as evidenced by increase
      in DNA, protein and collagen content of granulation tissues. Quicker and better
      maturation and crosslinking of collagen was observed in the extract-treated rats,
      as indicated by the high stability of acid-soluble collagen and increase in
      aldehyde content and tensile strength. The extract treated wounds were found to
      epithelialise faster and the rate of wound contraction was higher, as compared to
      control wounds. The results show that C. asiatica produced different actions on
      the various phases of wound repair.

PMID- 9246915
TI  - H2O2-induced lipid peroxidation in mitochondria of pulmonary vascular smooth
      muscle tissue and its modification by DFO, DMTU and DIDS.
AB  - Treatment of bovine pulmonary artery smooth muscle tissue mitochondria with H2O2
      stimulated iron release, hydroxyl radical (OH) production and lipid peroxidation.
      Pretreatment of mitochondria with deferoxamine (DFO) and dimethyl thiourea (DMTU)
      prevented OH production and markedly reduced lipid peroxidation without
      appreciably altering iron release caused by H2O2. Simultaneous treatment of
      either DFO or DMTU with H2O2 significantly reduced lipid peroxidation and also
      prevented OH production without causing marked decrease in iron release. In
      contrast, addition of DFO or DMTU even 2 min after treatment of the mitochondria
      with H2O2 did not significantly altered iron release, OH production and lipid
      peroxidation. Pretreatment of the mitochondria with 4,4'-dithiocyano-2,2'
      disulfonic acid stilbene (DIDS) markedly reduced lipid peroxidation without
      appreciably altering the increase in OH production and iron release caused by
      H2O2.

PMID- 9246916
TI  - Red cell enzymopathies in leukemias.
AB  - Red cell glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) levels
      were estimated in patients with leukemias, to see if there was a consistent
      enzyme defect and correlation of enzyme levels with stage of the disease with
      prognostic assessment. G6PD levels were found to be significantly increased or
      decreased in majority of the patients with acute leukemias. Increased activity
      was seen in majority of the patients with L1 and decreased activity in L2 subtype
      of acute lymphocytic leukemia (ALL). In chronic myeloid leukemia (CML) G6PD
      activity was consistently increased, with levels being highly elevated in chronic
      phase and moderately in blast phase. Variation in G6PD activity was found to be
      related to the stage of disease and was of prognostic significance. PK was found
      to be normal or decreased. Fetal haemoglobin levels were also estimated in 30
      patients with leukemias and were found to be elevated in most patients. Red cell
      G6PD may be useful for staging of the disease, as prognostic indicator and
      predictor of relapse.

PMID- 9246917
TI  - New blood free biphasic medium with haemoglobin for cultivation of Leishmania
      donovani promastigotes.
AB  - A simple biphasic growth medium for cultivation of L. donovani promastigotes is
      described. A successful attempt has been made to replace the blood/serum from
      regular medium by bovine hemoglobin powder. Medium is easy to prepare within 4
      hr. It is simple, reliable inexpensive and autoclavable. Ingredients used in the
      media preparation are readily available at low cost and components of the medium
      prepared in large quantities, could be stored at 4 degrees C for month without
      significantly altering their growth supporting potential. After an inoculation of
      1 x 10(5) promastigotes/ml, it was possible to cultivate 1-3 x 10(2)
      promastigotes/ml from the above described media.

PMID- 9246918
TI  - Bromo-deoxyuridine based assay for detection of parasite and drug sensitivity in
      Plasmodium falciparum in vitro.
AB  - A non-radioactive, thymidine analogue-bromodeoxyuridine (Brdu), derivative of
      uridine has been used for incorporation in DNA in culture of P. falciparum at
      various dosages and at different time period. Parasite growth rate and effect of
      chloroquine in culture were monitored by microscopic observation of stained
      smears and incorporation of Brdu molecules were visualized by immunofluorescence
      and measured by enzyme immuno assay using anti-Brdu. Uptaking of Brdu in parasite
      is slower unlike tumour cells. A positive correlation between parasite growth and
      Brdu uptake measurement by ELISA has been observed.

PMID- 9246919
TI  - Effect of insecticidal crystal proteins of Bacillus thuringiensis on human
      erythrocytes in vitro.
AB  - Effect of intact and alkali solubilized insecticidal crystal protein (ICP)
      preparations from a mutant strain of B. thuringiensis var. israelensis (VCRC
      MB24) and the wild type strain (VCRC B17) in vitro on human erythrocytes with
      respect to lipid peroxidation, osmofragility and membrane bound enzymes was
      determined. The alkali solubilized ICPs of both B. thuringiensis strains caused
      increased lipid peroxidation, decreased resistance to hypotonic lysis and
      reduction in the activity of membrane bound enzymes. On the contrary, the intact
      ICPs did not produce any such adverse effect on RBCs under the same experimental
      conditions. It is suggested that the ICPs are safe when they are intact when
      compared with solubilized ones.

PMID- 9246920
TI  - Antagonistic activity of Lactobacillus acidophilus fermented milk against
      different pathogenic bacteria.
AB  - Lactobacillus acidophilus strains tested showed inhibitory activity towards
      Salmonella typhi, Staphylococcus aureus, Escherichia coli, Proteus vulgaris and
      Yersinia enterocolitica. However, wide variations in the activity of the strains
      were observed. Antagonistic activity of the strains exhibited high heat stability
      (120 min at 92 degrees C, 15 min at 121 degrees C) but it was markedly influenced
      by changes in pH. Effect of kind of milk on antagonistic activity was variable,
      whereas skimming had no significant effect.

PMID- 9246921
TI  - Toxigenicity of Edwardsiella tarda isolates of fish and pig origin in
      experimental models.
AB  - Indian isolates of E. tarda from fish (7) and pigs (2) were examined for their
      enterotoxigenicity/cytotoxigenicity in rabbit ligated ileal loop (RLIL), suckling
      mouse, rabbit skin and Vero cell monolayers. Cell free culture filtrates (CFCF)
      of isolates from fish and pigs, induced blood tinged fluid accumulation in RLIL,
      increased vasopermeability in rabbit skin, and caused cytopathic effect in Vero
      cells but could not induce fluid accumulation in suckling mouse. CFCFs lost their
      activity on heating at 63 degrees C for 30 min or 72 degrees C for 15 sec, and
      also at pH < or = 4.5 or > or = 8.5. The toxic factor was released
      extracellularly and was nondializable.

PMID- 9246922
TI  - An extracellular phosphatase from Aspergillus fumigatus.
AB  - A potential producer of extracellular phosphatase has been isolated and
      identified as A. fumigatus. The fungal phosphatase is active in pH range 5 to 8
      and its temperature optimum is 65 degrees C. The mineralisation of organic
      phosphates present in Neem cake and press mud by this enzyme has been
      demonstrated.

PMID- 9246923
TI  - Inhibition of rat brain nitric oxide synthase activity by cyclosporin-A.
AB  - Cyclosporin-A, a potent immunosuppressive agent is known to induce cellular toxic
      side effects by way of altering calcium homeostasis, including calcium/calmodulin
      mediated events. We studied the in vitro and in vivo effects of cyclosporin-A on
      rat brain nitric oxide synthase activity (the enzyme that mediates the conversion
      of L-arginine to citrulline and NO). CsA in concentrations of 22-4400 nM
      inhibited rat brain NOS activity in vitro and in 10 or 25 mg/kg wt/4 weeks of CsA
      treated rat brains in vivo. We report here that CsA by way of interfering with
      rat brain Ca2+/CaM mediated events may inhibit its NOS activity which ultimately
      may result in neurotoxicity.

PMID- 9246924
TI  - Effect of verapamil on cadmium induced hypertension in rats.
AB  - The effect of cadmium acetate (0.1, 0.3, 1.0 mg/kg, i.v.) alone and following
      verapamil (2.5 mg/kg, i.v.), in male Sprague Dawley (S-D) rats on blood pressure
      (BP) and heart rate (HR) were examined. Cadmium acetate produced dose dependent
      effect on BP and HR. Cadmium injected intravenously in different doses produced
      initial transient fall followed by a persistent rise in blood pressure and heart
      rate. Verapamil pretreatment attenuated the BP and HR responses in rats. These
      findings indicate that two blockers of calcium channels produce different effects
      on BP and HR in rats.

PMID- 9246925
TI  - Indirect enzyme-linked immunosorbent assay (ELISA) for monitoring antibodies in
      rainbow trout Oncorhynchus mykiss.
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) has been described to
      detect and measure the antibodies in O. mykiss against a lambda bacteriophage
      antigen (strain c1187 Sam7). Antibodies were first detected six days after the
      first intraperitoneal injection and by day 21 all fish were positive. Maximum
      mean titres were detected on day 30 (3 days after the second injection). The mean
      titre declined by day 33 which was 6 days after second injection and remained
      constant from day 39 to day 45. The results suggest that immune response in a
      rainbow trout occurred faster and the fish were able to mount a very good
      response to viruses.

PMID- 9246926
TI  - Thermostable alpha-amylase production using Bacillus licheniformis NRRL B14368.
AB  - Maximum amount of extracellular alpha-amylase of B. licheniformis NRRL B14368 was
      obtained at the stationary phase. Highest yield of alpha-amylase was achieved
      with high level of crude protein and low carbohydrate level. There was a
      catabolite repression in the organism. Protease was produced concurrently with
      alpha-amylase. It was also observed that soyabean acts as an inhibitor of the
      protease. Optimum pH and temperature of alpha-amylase were 5-7 and 76 degrees C
      respectively. It was also observed that alpha-amylase production was a non-growth
      associated product. Maltose was an excellent inducer for alpha-amylase
      production. Ca2+ (0.01 M) increased the thermostability of the enzyme. Alpha
      amylase purification studies were carried out by using isopropanol, acetone,
      ammonium sulphate solution, ion exchange chromatography. Acetone was found most
      suitable for the separation of alpha-amylase. Protein recovery and relative
      enzyme activity (as compared to that of the maximum activity of the crude enzyme)
      were 30.77% and 3.03 respectively.

PMID- 9246927
TI  - The not-so-silent couple in the individual.
AB  - This paper aims to examine two often separate areas of analytical enquiry, the
      nature of the self, with its foundation in the concept of a primary self which
      may achieve a sense of coherence over time, and the nature of internal objects, a
      concept that forms the basis of theories concerning part selves and sub
      personalities. It is argued that these concepts might be integrated to provide a
      unified model of the self, thereby integrating theoretically disparate aspects of
      mental structure and functioning. Through an examination of clinical material,
      the archetype of the coniunctio is evoked to offer an understanding of how, in
      the absence of a stable conjunction of (maternal) reverie and (paternal) thinking
      functions, a series of linked but oppositional internal couples may be created
      which lends to the self the experience of a combined and sustaining inner couple.
      The internal couple creates a source of psychological survival for the self, with
      the function of providing a reliable structure in which the processes of the self
      may unfold, but equally requiring strict adherence to a pernicious system of
      internal defences that allows for very little interaction with others outside the
      self. At the same time, these defences inevitably become blocks to further
      development, and the work of transformation is thwarted. For transformation to
      occur, it is necessary for the self to find another, often the analyst, who may
      be allowed to partake in the internal conjunction, thereby promoting a better
      grounding for the self.

PMID- 9246928
TI  - The psychosomatic symptom and the self: a sirens' song.
AB  - This paper examines the symbolic nature of the psychosomatic symptom. It is
      suggested that the psychosomatic symptom is an informationally rich symbolic
      derivative of the Self that serves to focus attention on developmental
      disturbances in the archetypal processes of constructing body image and
      interpreting dysphoric somatic sensations. Clinical examples are offered to
      illustrate the changing nature of the psychomatic symptom in society. The
      therapeutic importance of monitoring affectual transactions in the transference
      countertransference field is stressed.

PMID- 9246929
TI  - Self as the feminine principle.
AB  - In analytical psychology, ego is associated with consciousness and the masculine
      principle. Although the feminine principle generally characterizes the
      unconscious, it was not assigned a psychic structure equivalent to the ego. This
      paper proposes a model of the psyche where self and ego are the major modes of
      psychic experience. The self as the 'being' mode represents the feminine
      principle and functions according to primary process; the ego represents 'doing',
      the masculine principle and secondary process. Feminine and masculine principles
      are considered to be of equal significance in both men and women and are not
      limited to gender. Jung's concept of the self is related to the Hindu
      metaphysical concepts of Atman and Brahman, whose source was the older Aryan
      nature-oriented, pagan religion. The prominence of self in analytical psychology
      and its predominantly 'feminine' symbolism can be understood as Jung's reaction
      to the psychoanalytic emphasis on ego and to Freud's 'patriarchal' orientation.
      In Kabbalah, a similar development took place when the feminine principle of the
      Shekinah emerged in a central, redemptive role, as a mythic compensation to the
      overtly patriarchal Judaic religion. In the proposed model of the psyche neither
      ego nor self represents the psychic totality. The interplay of both psychic
      modes/principles constitutes the psyche and the individuation process.

PMID- 9246930
TI  - The creative potential of play and regression in analytical training: a personal
      reflection.
AB  - The seminar group can serve as a framework in which to meet the fear generated
      during training. The group can become a maddening environment, but on occasions
      when it is experienced by the trainee as good enough, it can act like a playgroup
      which facilitates development. Experiences in the group can be viewed from the
      perspectives of group dynamics or of transference phenomena which embody
      regression. When this regression enables scope for play it can serve in the
      interests of ego development in the process of discovering the sort of analyst
      the trainee is becoming as the training unfolds. During play aspects of oneself
      can merge, then differentiate again. They can have different meanings at the same
      time. The rational and emotional, the adult and the childlike are all given a
      place in play.

PMID- 9246931
TI  - [Valproate i.v. Survey of its clinical application].

PMID- 9246932
TI  - Direct regulation of mammalian reproductive organs by serotonin and melatonin.

PMID- 9246933
TI  - The desensitization of oxytocin receptors in human myometrial cells is
      accompanied by down-regulation of oxytocin receptor messenger RNA.
AB  - We have recently provided evidence for the desensitization of oxytocin receptors
      in human myometrial cells. In the present study, we have investigated the
      possible mechanisms by which oxytocin (OT) might regulate OT receptor density.
      The steady state level of OT binding in cultured myometrial cells was 220 x 10(3)
      binding sites/ cell, but this was time-dependently reduced to 27 x 10(3)
      sites/cell by exposure to OT for up to 20 h. Similarly, OT exposure decreased the
      binding of OT to cell membranes. In contrast, Western blotting data showed that
      the total amount of OT receptor protein was not affected by OT treatment for up
      to 48 h. Flow cytometry experiments demonstrated that OT receptors are not
      internalized during prolonged exposure of the cells to OT. However, RNase
      protection assays and Northern analysis showed that OT receptor mRNA was reduced
      by OT treatment to reach a new low steady state level with a time course similar
      to that of the disappearance of cell surface OT binding sites. Possible
      mechanisms involved in mRNA down-regulation include transcriptional suppression
      and destabilization of mRNA by RNA binding proteins.

PMID- 9246934
TI  - Early diabetes-induced changes in rat jejunal glucose transport and the response
      to insulin.
AB  - The effects of 1 day of streptozotocin-induced diabetes in rats on glucose
      transport across the brush border membrane (BBM) and basolateral membrane (BLM)
      prepared from jejunal enterocytes has been studied. The effects on glucose
      transport of treatment of diabetic animals with insulin to reduce to normal the
      elevated blood glucose levels has also been assessed. The maximum capacity (Vmax)
      for SGLT1-mediated glucose uptake by BBM vesicles was unaffected by diabetes or
      insulin treatment of diabetic rats. In contrast, Vmax for BLM glucose uptake was
      increased by 206% in diabetes, a response that could not be reversed by treatment
      with insulin. Western blotting of BBM for SGLT1 protein revealed a single band
      with a molecular weight of 73 kDa and the intensity of this band was unaffected
      by diabetes. However, an increased level of GLUT2 was noted in diabetic BLM and
      this was not a consequence of changes in glycaemic or insulin status. Diabetes
      hyperpolarised the BBM, implying an increased driving force for Na(+)-sugar co
      transport but insulin treatment only partially reversed this enhanced potential
      difference. Benzamil (2 microns), an epithelial Na+ channel blocker,
      hyperpolarised the BBM of control but not diabetic enterocytes, implying that a
      reduced Na+ permeability was responsible for the diabetic hyperpolarisation. It
      was concluded that in early diabetes, before the onset of hyperphagia, a greater
      driving force for Na(+)-dependent BBM sugar transport together with increased
      GLUT2 activity at the BLM promotes sugar movement across the enterocyte. Possible
      triggers for the transport responses are discussed.

PMID- 9246935
TI  - Cerebellin and cerebellin mRNA in the human brain, adrenal glands and the tumour
      tissues of adrenal tumour, ganglioneuroblastoma and neuroblastoma.
AB  - The expression of cerebellin and cerebellin mRNA was studied by radioimmunoassay
      and Northern blot analysis in the human brain, adrenal gland and the tumour
      tissues of adrenal tumour, ganglioneuroblastoma and neuroblastoma. Immunoreactive
      cerebellin was detected in every region of brain studied, with the highest
      concentrations found in the hemisphere of the cerebellum (424.2 +/- 12.6 pmol/g
      wet weight, n = 6, mean +/- S.E.M.) and the vermis of the cerebellum (256.8 +/-
      30.5 pmol/g wet weight). Immunoreactive cerebellin was also detected in the
      pituitary (8.2 +/- 1.8 pmol/g wet weight), the spinal cord (3.3 +/- 0.3 pmol/g
      wet weight) and the normal parts of adrenal glands (2.98 +/- 0.37 pmol/g wet
      weight, n = 9) and some tumour tissues, such as phaeochromocytomas, cortisol
      producing adrenocortical adenomas, ganglioneuroblastomas and neuroblastomas.
      Northern blot analysis showed that cerebellin mRNA was highly expressed in the
      hemisphere and vermis of the cerebellum. Cerebellin mRNA was also expressed in
      other regions of the brain and the tumour tissues of phaeochromocytoma, cortisol
      producing adrenocortical adenoma, ganglioneuroblastoma and neuroblastoma.
      Immunocytochemistry of the normal adrenal gland showed that immunoreactive
      cerebellin was localized in the adrenal medulla. The present study has shown the
      expression of cerebellin and cerebellin mRNA, not only in the cerebellum but also
      in other regions of the brain and some tumours, such as cortisol-producing
      adrenocortical adenoma, phaeochromocytoma and neuroblastoma. These findings
      suggest possible pathophysiological roles of cerebellin peptides, not only in the
      cerebellum, but also in the extra-cerebellar tissues.

PMID- 9246936
TI  - Modulation of the insulin-like growth factor-binding proteins by follicle size in
      the human ovary.
AB  - The IGFs are believed to play an important role in the regulation of
      steroidogenesis and follicular maturation in the human ovary. The activities of
      the IGFs are regulated by a family of binding proteins (IGFBPs) which are subject
      to a number of potential post-translational modifications. The aim of this study
      was to investigate both the production and modification of the IGFBPs in
      follicular fluid and in medium conditioned by granulosa cells and theca from
      individual follicles at different stages of maturation. In follicular fluid from
      healthy, dominant follicles there was an increase in the amount of IGFBP-2, -3
      and -4 present as lower molecular weight forms (23 kDa, 29 kDa and 16.5 kDa
      respectively) in comparison to that seen in atretic follicles from the same
      ovary. Furthermore for IGFBP-4, this fragmentation was confirmed to be
      attributable to the presence of a specific protease which could be inhibited not
      only by the addition of metal ion chelators or serine protease inhibitors, but
      also by the addition of other recombinant unsaturated IGFBPs, particularly IGFBP
      3. IGF-I did not modulate the activity of the IGFBP-4 protease in solution but
      was able to prevent the inhibition seen with IGFBP-3. Analysis of granulosa cell
      conditioned medium from the same series of healthy and atretic follicles revealed
      that IGFBP-2 and -4 were the predominant IGFBPs with no fragments seen on
      immunoblotting. In contrast, IGFBP-3 in conditioned medium from theca of atretic
      follicles was always found as an intact doublet, but was found partially
      fragmented (30 and 32 kDa) in medium conditioned by theca from healthy, dominant
      follicles with the proportion of IGFBP-3 in this lower molecular weight or
      fragmented doublet increasing with follicular maturation. A similar situation was
      also found for IGFBP-4 with the progressive increase in the amount of the 15 and
      16.5 kDa fragments. IGFBP-2 was always found to be intact. Finally, IGFBP
      production from stroma explants was also examined. This revealed a wide variation
      in IGFBP pattern between different ovaries, although there was a remarkable
      degree of consistency between different stroma explant cultures from the same
      ovary. Immunoblotting for IGFBP-3 revealed that, where present, it existed as
      both an intact and a lower molecular weight doublet and that IGFBP-2 was again
      always found to be intact. In conclusion we have demonstrated alterations in the
      proteolytic modification of the IGFBPs which differ in the various follicular
      compartments and are closely linked to the stage of follicular development.

PMID- 9246937
TI  - Platelet-derived growth factor, insulin-like growth factors, fibroblast growth
      factors and transforming growth factor beta do not account for the cell growth
      activity present in bovine milk.
AB  - Cation-exchange chromatography effectively concentrates the cell growth activity
      present in whey and we have used this process as a basis to characterise further
      the growth factors present in bovine milk. Under neutral conditions, total
      bioactivity in the growth factor-enriched cation-exchange fraction
      chromatographed with an apparent molecular mass of 80-100 kDa. In contrast, acid
      gel-filtration chromatography resolved two peaks of cell growth activity. A peak
      at 15-25 kDa contained the bulk of growth activity for Balb/c 3T3 fibroblasts
      while bio-activity for L6 myoblasts and skin fibroblasts eluted with a molecular
      mass of 6 kDa. A peak of inhibitory activity for Mv1Lu and MDCK cells also eluted
      at 15-25 kDa. Both IGF-I and IGF-II were purified from fractions that eluted at 6
      kDa, although the IGF peptides alone did not account for the total bioactivity
      recovered. Platelet-derived growth factor (PDGF), identified by radioreceptor
      assay, eluted at a slightly higher molecular mass than the peak of growth
      activity for Balb/c 3T3 cells, and an anti-PDGF antibody was without effect on
      the growth of Balb/c 3T3 cells in response to the whey-derived factors. Further
      purification of the inhibitory activity for epithelial cells yielded a sequence
      for transforming growth factor beta (TGF-beta), and all inhibitory activity for
      Mv1Lu cells was immunoneutralised by an antibody against TGF-beta. In contrast,
      this antibody decreased the growth of Balb/c 3T3 fibroblasts in the whey-derived
      extract by only 10%. Finally, a cocktail of recombinant growth factors containing
      IGF-I, IGF-II, PDGF, TGF-beta and fibroblast growth factor 2 stimulated growth of
      Balb/c 3T3 cells to a level equivalent to only 51% of that observed in the milk
      derived growth factor preparation. We conclude that: (i) cell growth activity
      recovered from bovine whey is present in acid-labile high molecular weight
      complexes; (ii) all cell growth inhibitory activity for epithelial cells can be
      accounted for by TGF-beta; (iii) IGF-I and IGF-II co-elute with the major peak of
      activity for L6 myoblasts and skin fibroblasts, although the IGF peptides alone
      do not explain the growth of these cells in the whey-derived extract; and (iv)
      neither PDGF nor TGF-beta account for the 15-25 kDa peak of Balb/c 3T3 growth
      activity. These data suggest the presence of additional mitogenic factors in
      bovine milk.

PMID- 9246938
TI  - Age and sex related differences in serum levels of unconjugated
      dehydroepiandrosterone and its sulphate in normal subjects.
AB  - Dehydroepiandrosterone sulphate (DHEAS) and unconjugated dehydroepiandrosterone
      (DHEA) have been determined in the blood serum of normal subjects of both sexes
      from 1 month to 100 years of age. In total, 92 girls, 49 boys, 211 women and 110
      men were investigated. The effects of age and sex on the levels of the hormones
      were measured. DHEAS levels declined rapidly during the first year of life and
      were maintained at a minimum level for 5 years. They increased significantly from
      6 to 7 years of age and reached maximum levels in women at about 24 years and in
      men at about 30 years of age. They then declined rapidly in both sexes but the
      fall which occurred after 50 and 60 years of age respectively was only moderate.
      Age-related unconjugated DHEA levels were different. After the first month of
      life DHEA levels were relatively high and declined more slowly. The minimum level
      was observed in girls between 5 and 7 years and in boys between 5 and 9 years of
      age. A significant rise then began and levels reached a maximum in women as well
      as in men at about 20 years of age. In men levels then declined up to the age of
      80. In women the DHEA levels declined during the next 15 years and from
      approximately 36 years of age they again rose significantly up to a second peak.
      A mild but significant decline then resumed. There was a difference in the levels
      of DHEA and DHEAS depending on sex. Unlike DHEAS, unconjugated DHEA was higher in
      women than in men. However, this difference was significant only in some age
      groups: during puberty (between 11 and 15 years of age), in the premenopausal
      period (between 36 and 45 years of age) and in the older group (after 60 years of
      age). Age- and sex-related dependencies were different between DHEAS and DHEA.
      They indicate the possible variable secretion and dynamics of their
      (inter)conversion. We have concluded that DHEA measurements cannot be a
      substitute for DHEAS and vice versa.

PMID- 9246939
TI  - Thyroid hormone, vitamin D and retinoid receptor expression and signalling in
      primary cultures of rat osteoblastic and immortalised osteosarcoma cells.
AB  - 3,5,3'-Tri-iodothyronine (T3), 1 alpha,25(OH)2-vitamin D3 (D3) and retinoids
      activate related nuclear receptors which interact by heterodimerisation to
      regulate gene expression. Actions of each hormone are discrete and may be
      specified by changes in the relative concentrations of their receptors (T3R,
      vitamin D receptor (VDR), retinoic acid receptor (RAR), retinoid X receptor
      (RXR)). T3, D3 and retinoids are essential for skeletal development and
      maintenance and we have previously shown complex interactions amongst their
      signalling pathways in osteosarcoma cells. In these studies we demonstrate that
      similar T3R, VDR, RAR and RXR proteins are co-expressed in both osteoblast
      lineage cell primary cultures and osteosarcoma cells by Western blotting. We
      investigated whether hormone interactions in bone result from changes in receptor
      stoichiometry. Cells were treated with combinations of T3, D3, 9-cis retinoic
      acid (9-cis RA) and all-trans retinoic acid (RA) that are known from previous
      studies to produce complex cell specific responses. No alteration in expression
      of any receptor protein was seen in response to any hormone combination in three
      phenotypically distinct osteosarcoma cell lines. Thus, in contrast to studies of
      overexpressed receptors in vitro, changes in the physiological concentrations of
      endogenous T3R, VDR, RAR and RXR do not specify discrete hormone actions in
      osteoblastic cells. Other unidentified factors are likely to modulate hormone
      action in these bone cells.

PMID- 9246940
TI  - Oestrogen and progesterone control basic fibroblast growth factor mRNA in the rat
      uterus.
AB  - Cell proliferation and differentiation in the rodent uterus are probably
      controlled by the interaction of female sex steroids with polypeptide growth
      factors. Uterine basic fibroblast growth factor (bFGF) mRNA was measured by RNase
      protection during the time (days 2-4) of endometrial cell proliferation in the
      pregnant rat. bFGF transcripts were detected at each of the 3 days of pregnancy
      examined. To investigate the influence of oestrogen and progesterone on bFGF mRNA
      accumulation, ovariectomized rats were treated with oestradiol for 48 h followed
      by a single injection of oestradiol, progesterone, the two steroids co-injected
      or oil vehicle alone. Uterine RNA was collected 6 h after the last hormone
      injection. Steroid treatments increased steady-state uterine bFGF mRNA compared
      with vehicle control animals as measured by RNase protection. Northern blot
      analysis of c-fos and c-jun mRNAs from these same treatment groups revealed
      increased protooncogene expression in the uterus of hormone treated rats compared
      with the control animals. Temporal analysis of bFGF mRNA in ovariectomized rats
      at 1, 3 and 6 h after acute oestrogen and oestrogen-progesterone co
      administration showed a dual pattern of transcript accumulation. Both hormone
      treatments increased bFGF mRNA within 1 h compared with vehicle injected rats. Co
      administration of the two hormones, however, repressed bFGF mRNA accumulation
      relative to oestrogen at 3 and 6 h. Together, these studies provide evidence that
      bFGF control of uterine cell proliferation in pregnant rats can occur from newly
      synthesized bFGF. Moreover, the results suggest that progesterone is a potent
      stimulator of bFGF expression in the uterus.

PMID- 9246941
TI  - Effect of monensin on 2-deoxyglucose uptake, the insulin receptor and
      phosphatidylinositol 3-kinase activity in rat muscle.
AB  - Preincubation of rat soleus muscle with 1 and 10 microM monensin for 2 h
      increased the subsequent basal 2-deoxyglucose uptake by muscle 76 and 121%
      respectively. Under the same conditions, monensin decreased the insulin
      stimulated (1 mU/ml) 2-deoxyglucose uptake by 29 and 37% respectively. The
      monensin-induced augmentation of basal 2-deoxyglucose uptake was inhibited 92% by
      cytochalasin B suggesting that the uptake is mediated by glucose transporters.
      Monensin did not increase the cellular accumulation of L-glucose in muscle
      indicating that it does not affect the cell membrane integrity. Neither the
      stimulatory effect of monensin on basal 2-deoxyglucose uptake nor the opposite,
      inhibitory action of monensin on the insulin-stimulated 2-deoxyglucose uptake
      were influenced by the removal of Ca2+ from the medium or by dantrolene, an
      inhibitor of Ca2+ release from the sarcoplasmic reticulum, suggesting that the
      actions of monensin are not mediated by calcium. Monensin had no effect on muscle
      ATP concentration. The monensin-induced augmentation of basal 2-deoxyglucose
      uptake was neither associated with stimulation of muscle phosphatidylinositol 3
      kinase activity nor inhibited by wortmannin, demonstrating that the increase in
      basal 2-deoxyglucose uptake is not mediated by activation of phosphatidylinositol
      3-kinase. The inhibition of insulin-stimulated 2-deoxyglucose uptake by monensin
      was associated with a 31% decrease in the abundance of insulin receptors in
      muscles, a 64% decrease in the insulin-induced autophosphorylation of the insulin
      receptor beta-subunit, and a 44% reduction of the insulin-stimulated
      phosphatidylinositol 3-kinase activity. Addition of monensin into the
      phosphatidylinositol 3-kinase reaction had no effect on the activity of the
      enzyme, demonstrating that the inhibition in monensin-treated muscles is indirect
      and occurs upstream of phosphatidylinositol 3-kinase. It is concluded that
      monensin has a dual effect on 2-deoxyglucose uptake by skeletal muscle: it
      stimulates basal uptake but inhibits the insulin-stimulated uptake. The primary
      cause of the latter, inhibitory effect of monensin is at the level of the insulin
      receptor.

PMID- 9246942
TI  - High levels of fetal membrane activin beta A and activin receptor IIB mRNAs and
      augmented concentration of amniotic fluid activin A in women in term or preterm
      labor.
AB  - The aim of the present study was to evaluate whether spontaneous labor at term
      and pathological preterm labor are associated with changes in the expression of
      activin A and activin receptor mRNAs in fetal membranes. In addition, amniotic
      fluid activin A concentration in women delivering at term or undergoing preterm
      labor was also measured. The expression of activin beta A subunit and activin
      receptor type II and type IIB mRNAs was assessed by reverse transcriptase-PCR on
      specimens of amnion and chorion collected from patients delivering at term or
      undergoing preterm labor. Control specimens were collected from women delivered
      by elective cesarean section who had not experienced labor. A specific two-site
      ELISA was used to measure activin A concentrations in the amniotic fluid. A cross
      sectional study of amniotic fluid retrieved by amniocentesis from 109 pregnant
      women was carried out. Patients were classified into the following groups: (1)
      healthy controls at term but not in labor (n = 25); (2) healthy controls at term
      in spontaneous labor (n = 40); (3) healthy controls between 23 and 36 weeks of
      gestation (n = 12); (4) patients in preterm labor responding to tocolytic
      treatment (n = 19); (5) patients in preterm labor with subsequent delivery (n =
      13). Activin beta A subunit and activin receptor type IIB mRNA levels in both the
      chorion and amnion in women delivering at term or after preterm labor were
      significantly higher than in women delivering without undergoing labor (P <
      0.01). Expression of activin receptor type II mRNA in membranes did not differ
      among the three groups of women. Amniotic fluid activin A concentration in
      patients in labor was significantly higher than in those at term but not in labor
      (P < 0.01). Patients in preterm labor had significantly higher amniotic fluid
      activin A concentrations than women at the same stage of gestation (P < 0.01).
      The highest values were found in women undergoing preterm labor and subsequent
      delivery. In conclusion, spontaneous labor and preterm labor are characterized by
      increased synthesis and release of activin A from amniotic and chorionic cells
      and by an augmented expression of activin type IIB receptor.

PMID- 9246943
TI  - The expression of parathyroid hormone-related protein mRNA and immunoreactive
      protein in human amnion and choriodecidua is increased at term compared with
      preterm gestation.
AB  - Parathyroid hormone-related protein (PTHrP) gene expression and/or immunoreactive
      protein have previously been identified in the uterus and intrauterine
      gestational tissues. The putative roles of PTHrP during pregnancy include
      vasodilatation, regulation of placental calcium transfer, uterine smooth muscle
      relaxation and normal fetal development. The aims of this study were 1) to
      determine the tissue-specific and temporal expression of PTHrP mRNA and
      immunoreactive protein in human gestational tissues collected at preterm and
      term; and 2) to determine the effect of labour on PTHrP expression by collecting
      these tissues from women undergoing elective caesarean section (before labour),
      intra-partum caesarean section during spontaneous-onset labour (during labour),
      and women with spontaneous labour and normal vaginal delivery (after labour).
      Total RNA and protein were extracted from placenta, amnion (over placenta and
      reflected) and choriodecidua for analysis by Northern blot (using a specific
      human PTHrP cDNA probe), and by N-terminal PTHrP RIA respectively. In amnion over
      placenta, reflected amnion and choriodecidua both PTHrP mRNA relative abundance
      and immunoreactive protein were significantly elevated at term compared with
      preterm (P < 0.01). At term, both PTHrP and its mRNA were significantly greater
      in amnion than in placenta and choriodecidua (P < 0.05). Also, both PTHrP and its
      mRNA were significantly elevated in amnion over placenta compared with reflected
      amnion (P < 0.05). The expression of PTHrP and its mRNA did not change in
      association with term labour or rupture of the fetal membranes, therefore this
      study provides no evidence for a specific PTHrP role in the onset and/or
      maintenance of term labour. However, the significant up-regulation of PTHrP mRNA
      and protein in the fetal membranes at term compared with preterm suggests an
      important role in late human pregnancy.

PMID- 9246944
TI  - Evidence suggesting that cadmium induces a non-thyroidal illness syndrome in the
      rat.
AB  - The effect of in vivo administration of cadmium chloride on the pituitary
      thyroidal axis was assessed in 200 g body weight Wistar rats. A dose of 2.5 mg/kg
      body weight was injected i.v. 24 h before the experiments were initiated. Plasma
      thyroxine (T4) and tri-iodothyronine (T3) concentrations in cadmium-treated rats
      were significantly (P < 0.01) decreased, whereas plasma TSH failed to increase in
      response to low T4 and T3. However, the TSH response to TRH and the pituitary
      content of TSH in these rats were both normal. Cadmium induced a significant (P <
      0.01) decrease in 4-h thyroidal 131I uptake and in thyroid/plasma radioactivity
      ratio. The in vitro conversion of T4 to T3 in the pituitary was significantly (P
      < 0.01) blocked by cadmium whereas there was no in vivo effect. Parameters of
      peripheral T4 kinetics in cadmium-treated rats, such as metabolic clearance rate
      (P < 0.01), fractional turnover rate (P < 0.01), absolute disposal rate (P <
      0.05), urinary clearance (P < 0.05) and faecal clearance (P < 0.05), were all
      decreased by cadmium. The lack of response of TSH to low plasma T4 and T3 and the
      normal response to exogenous TRH in this and in other non-thyroidal illness
      syndromes produced by other pathologies suggest a decreased stimulation of
      pituitary thyrotrophs by endogenous TRH.

PMID- 9246945
TI  - Characterization of the binding of 3,3'-di-iodo-L-thyronine to rat liver
      mitochondria.
AB  - The binding of labelled 3,3'-di-iodo-L-thyronine (3,3'-T2) to isolated rat liver
      mitochondria has been characterized. Specific binding could be detected only in
      the inner mitochondrial membrane, not in other mitochondrial subfractions. The
      composition of the incubation medium influenced the binding capacity, the best
      combination of high specific binding and low non-specific binding being observed
      in phosphate buffer, pH 6.4. The specific binding of 3,3'-T2 to mitochondria
      requires low ionic strength: concentrations of K+ and Na+ higher than 10 mmol/l
      and 0.1 mmol/l respectively resulted in a decreased binding capacity. The optimal
      calcium ion concentration was in the range 0.01-1.0 mmol/l. Varying magnesium
      ion, over the range of concentrations used (0.1-100 mmol/l), had no effect. Both
      ADP and ATP, at over 1 mmol/l, resulted in an inhibition of the specific binding.
      Incubation with protease resulted in a decrease in specific binding and an
      increase in non-specific binding, thus indicating the proteic nature of the
      binding sites. In addition to the above factors in the local environment the
      thyroid state of the animal might influence the 3,3'-T2-binding capacity. In
      fact, the thyroid state of the animal seemed not to have an influence on the
      affinity constant, but it did affect binding capacity.

PMID- 9246946
TI  - Blockade of the neonatal increase in testosterone by a GnRH antagonist: the free
      androgen index, reproductive capacity and postmortem findings in the male
      marmoset monkey.
AB  - Male marmoset monkeys which had received gonadotrophin-releasing hormone (GnRH)
      antagonist treatment as neonates to block the postnatal increase in testosterone
      were studied, with the object of determining potential long-term effects of
      treatment on the reproductive system, including tests of fertilising capacity. To
      obtain information on the nature of the circulating testosterone during this
      neonatal period, sequential blood samples were collected from a further control
      group of ten neonates, aged between birth and 3 months, and from 11 adult,
      normally fertile males, to examine the relative proportions of free, sex-hormone
      binding globulin (SHBG)-bound, and non-SHBG-bound testosterone. In control
      neonates, 11% of the circulating testosterone was free, and a further 19% non
      SHBG-bound, and therefore presumed to be biologically available. The remaining
      70% was SHBG-bound and considered to be biologically inert. This indicates that
      the neonatal increase in marmoset testosterone has a biological function. After
      pairing with females, time to first positive vaginal lavage and first delivery
      was similar for females, whether they were with control or treated male partners.
      Pregnancy outcome, in terms of number of young delivered and sex ratio, did not
      differ. This indicates that there appear to be no long-term sequelae in terms of
      procreative ability in male marmosets treated neonatally with a GnRH antagonist.
      Autopsy revealed no gross changes, except in the thymus, which was significantly
      heavier in the treated group. These results indicate that, although the
      circulating testosterone is in a biologically active form during the neonatal
      period, inhibition of testicular function in the neonate is without major effect
      on the adult male reproductive system. Treatment with a GnRH antagonist may have
      long-term effects on the immune system.

PMID- 9246947
TI  - Characterization of the AT1 angiotensin II receptor expressed in guinea pig
      liver.
AB  - In guinea pig hepatocytes angiotensin II induced phosphorylase a activation. This
      effect was mimicked by other angiotensins with the potency order: angiotensin II
      (EC50 approximately 1 nM) > angiotensin III (EC50 approximately nM) > angiotensin
      I (EC50 approximately 300 nM). The effect of 10 nM angiotensin II was blocked by
      the angiotensin II receptor AT1-selective antagonists irbesartan and losartan (Ki
      values of approximately 1 nM and approximately 10 nM for irbesartan and losartan
      respectively) but not by the AT2-selective antagonist PD123177. Similar data were
      obtained when the production of [3H]IP3 from [3H]myo-inositol-labeled cells was
      studied Angiotensin II induced a dose-dependent increase in [3H]IP3 production;
      the maximal effect (approximately 3-fold) was observed at a concentration of 10
      microM. This effect of angiotensin II was completely blocked by the AT1-selective
      antagonists irbesartan and losartan, but only in a very limited fashion by
      PD123177. [125I][Sar1-Ile8]angiotensin II bound with high affinity (approximately
      3.8 nM) to a moderately abundant number of sites (approximately 660 fmol/mg
      protein) in guinea pig liver membranes. Binding competition experiments indicate
      the following orders of potency for agonists: angiotensin II (approximately 1.5
      nM) > angiotensin III (approximately 7 nM) > angiotensin I (approximately 176
      nM), and for antagonists: irbesartan (approximately 0.5 nM) > losartan
      (approximately 36 nM) > > PD123177 (> > 10000 nM). The functional and binding
      data strongly indicate that the effects of angiotensin II were mediated through
      AT1 receptors. Expression of the mRNA for these receptors was confirmed by RT-PCR
      and hybridization of the reaction product with a radiolabeled rat AT1 receptor
      cDNA probe.

PMID- 9246948
TI  - Effects of vasopressin and elimination of corticotropin-releasing hormone-target
      cells on pro-opiomelanocortin mRNA levels and adrenocorticotropin secretion in
      ovine anterior pituitary cells.
AB  - Although arginine-vasopressin (AVP) is reported to produce greater ACTH
      biosynthetic and secretary responses than does corticotropin-releasing hormone
      (CRH) in sheep anterior pituitary cells, neither factor appears to increase pro
      opiomelanocortin (POMC) mRNA levels, as does CRH in the cells of some other
      species. Since only a fraction of cells that express POMC mRNA may be able to
      respond to AVP, the aim of this study was to further delineate the regulation of
      POMC mRNA in ovine anterior pituitary corticotrophs, as a whole and in functional
      subpopulations of corticotrophs. We measured the effects of AVP, CRH or
      activation of protein kinase C by phorbol myristate acetate (PMA) in cultured
      cells. We compared responses in intact populations with those of cultures from
      which CRH-target cells were pharmacologically eliminated. Dissociated adult ovine
      anterior pituitary cells were cultured overnight, treated with either vehicle
      (intact) or a CRH-toxin conjugate that specifically eliminates CRH-target cells
      (CRH-target-depleted), washed, returned to culture and subsequently challenged
      with vehicle, AVP (100 nM), CRH (10 nM) or PMA (1 microM) for 5 h. The media were
      assayed for ACTH by RIA and the cells for POMC mRNA by Northern blot analysis. In
      intact populations, AVP and CRH increased ACTH secretion from 6.5 +/- 1.2 to 216
      +/- 22 and 81 +/- 14 ng/well respectively, but only AVP caused an increase in
      steady-state POMC mRNA levels (+48 +/- 10%). Direct activation of protein kinase
      C with PMA mimicked the effect of AVP on ACTH secretion (318 +/- 16 ng/well), but
      did not alter POMC mRNA levels. In CRH-target-depleted populations, control ACTH
      secretion (11 +/- 3 ng/well) and POMC mRNA (+69 +/- 7%) were elevated, compared
      with intact populations. AVP (55 +/- 8 ng/well) and PMA (120 +/- 17 ng/ well),
      but not CRH, increased ACTH secretion; POMC mRNA was not significantly elevated
      by any of the treatments. Taken together, these data provide further support for
      the notion of dissociation between secretion of ACTH and expression of POMC mRNA,
      and demonstrate that AVP increases steady-state POMC mRNA levels in ovine
      anterior pituitary cells. The data are also consistent with the concept that
      complex interactions, possibly including those between cells, influence ACTH
      secretion and steady-state POMC mRNA levels.

PMID- 9246949
TI  - Mitogenic effects of thyroxine and TRH on thyrotrophs and somatotrophs of the
      anterior pituitary gland in thyroidectomized rats.
AB  - The question of whether thyroxine (T4) and TRH have a mitogenic effect on
      pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated.
      Mitoses were counted in hematoxylin-eosin-stained or periodic acid-Schiff
      hematoxylin-stained pituitary slides or immunostained for TSH or GH using male
      rats thyroidectomized for 5 months. Ten days before they were killed groups of
      rats were injected with different doses of T4 (0.5, 3 or 10 micrograms i.m. every
      second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days),
      or T4 plus TRH (same doses as above). Mitoses (stopped with colchicine) were
      counted in 1 mm2 areas at a magnification of x1000. In thyroidectomized rats,
      mitoses were not significantly increased and treatment with TRH or 0.5 microgram
      T4 alone in thyroidectomized rats did not affect mitotic counts. In
      thyroidectomized rats treated with higher doses of T4, mitoses were increased in
      a dose-dependent fashion. Simultaneous administration of TRH and T4 had a
      significant synergistic effect on pituitary mitoses in a T4 dose-dependent
      manner. The treatments also had differential effects on the relative percentages
      of cellular types in mitosis. Thus, 60% somatotrophs and 12.5% thyrotrophs were
      found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH
      groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28.5% and
      33.3% respectively. In thyroidectomized rats treated with low doses of T4,
      somatotrophs and thyrotrophs in mitosis increased to 38.4% and 80% respectively
      and, with simultaneous administration of a low dose of T4 plus TRH, although less
      effective than T4 alone, mitosis increased in somatotrophs and thyrotrophs to
      11.1% and 54.5% respectively. A high dose of T4 alone did not increase the
      mitotic figures in somatotrophs (38.8%), while it diminished the percentage of
      thyrotrophs to 25%. The administration of high doses of T4 plus TRH had an
      opposite effect on the mitotic figures of somatotrophs and thyrotrophs and thus
      the percentage of somatotrophs increased to 50% while thyrotrophs decreased to
      5.5%. Ten days of treatment with T4 were insufficient to reverse the histology to
      euthyroidism. It can be concluded that in long-standing hypothyroidism: (1)
      thyroid hormone replacement elicits a dose-dependent and differential
      proliferative response on pituitary thyrotrophs and somatotrophs, (2) TRH is
      devoid of mitogenic effects when administered alone and (3) the proliferative
      response of somatotrophs to T4 is enhanced by its co-administration with TRH,
      suggesting a permissive and/or synergistic effect of the thyroid hormone and TRH.

PMID- 9246950
TI  - Tri-iodothyronine increases insulin-like growth factor binding protein-4
      expression in rat hepatocytes.
AB  - Previous in vivo studies demonstrated significant variations in insulin-like
      growth factor binding protein-1 (IGFBP-1), IGFBP-2 and IGFBP-4 hepatic mRNAs
      and/or serum levels depending on the rat thyroid status. In this study we
      employed cultured hepatocytes from adult rats to demonstrate a possible direct
      regulation of these genes by tri-iodothyronine (T3). Northern blot analysis
      revealed that IGFBP-1 and -4 messages were clearly expressed, whereas IGFBP-2
      signal was barely detectable. No significant effects on IGFBP-1 mRNA level or on
      peptide secretion were detected in T3-cultured hepatocytes. In contrast,
      significant increases in IGFBP-4 mRNA steady-state levels as well as in IGFBP-4
      secretion were observed in hepatocytes cultured for 12-24 h in the presence of
      T3. The T3 effect on IGFBP-4 transcript levels appears to consist of enhanced
      gene transcription and is independent of ongoing protein synthesis. The T3
      increased IGFBP-4 expression in cultured hepatocytes is consistent with our in
      vivo experiments demonstrating an increase in hepatic IGFBP-4 mRNA and serum
      IGFBP-4 levels in T3-treated rats. Furthermore, significant decreases in hepatic
      IGFBP-4 message and serum IGFBP-4 levels were observed in hypothyroid rats
      compared with euthyroid controls. Our data establish an important direct role for
      thyroid hormone in regulating IGFBP-4 expression and consequently IGF activity.

PMID- 9246951
TI  - Thyroid hormone induces protein secretion and morphological changes in astroglial
      cells with an increase in expression of glial fibrillary acidic protein.
AB  - Thyroid hormone (T3) induces in vitro differentiation of astrocytes from the
      developing rat brain. T3 treatment induced the appearance of long processes in
      cultured cerebral hemisphere and mesencephalon astrocytes from embryonic and
      newborn rats. T3 treatment also produced a change in the morphology of cultured
      cerebellar astrocytes from 10-day-old rats, but not in cerebellar astrocytes from
      newborn rats. An increased expression of glial fibrillary acidic protein (GFAP)
      was also seen in the T3-treated newborn cerebral hemisphere and mesencephalic
      astrocytes. The morphological changes were induced earlier when the astrocytes
      were treated with conditioned medium (CM) obtained from cultures previously
      exposed to T3. Our results show that astrocytes from the developing rat brain are
      not homogeneous in their responsiveness to T3. Furthermore, the fact that CM
      produces a response similar to that obtained with T3 treatment but in less time,
      suggests that T3 might induce the secretion of factors by cultured astrocytes.
      These factors might, by an autocrine/paracrine effect, induce the expression of
      GFAP and differentiation in developing brain astrocytes.

PMID- 9246952
TI  - The effect of maternal protein deficiency during pregnancy and lactation on
      glucose tolerance and pancreatic islet function in adult rat offspring.
AB  - To test the hypothesis that poor foetal-neonatal nutrition predisposes adult
      animals to impaired glucose tolerance or diabetes, pregnant and lactating rats
      were fed a low (5%) protein diet and glucose tolerance and pancreatic islet
      function then assessed in the adult offspring. To expose any underlying defects
      the offspring were allowed access to a sucrose supplement (35%) or fed a high fat
      diet. Offspring born to low protein-fed females had significantly lower body
      weights than controls. In islets from previously malnourished rats, insulin
      release in batch incubations or perifusion was not significantly different to
      controls. In islets from previously malnourished animals fed sucrose, glucose
      stimulated insulin release was reduced in perifusion by 66% (P < 0.01) and batch
      incubations by 26-52% (6-16 mmol/l glucose, P < 0.01). Similarly, impaired
      secretory responses were found in islets from previously malnourished animals fed
      a high fat diet. These did not result from a reduced pool of releasable insulin,
      as arginine-stimulated secretion was not impaired. Rats previously malnourished
      showed a normal glucose tolerance. Glucose tolerance was impaired, however, in
      previously malnourished rats fed sucrose (area under the glucose tolerance test
      curve was increased by 42%, P < 0.05) but despite the reduced islet secretory
      responses was not significantly different to sucrose-fed controls (area increased
      by 54%, P < 0.05). Glucose tolerance was impaired in previously malnourished
      animals fed high fat diet (area increased by 48%, P < 0.05) more so than in high
      fat fed-controls (28% increase, NS). These data support the hypothesis that poor
      foetal-neonatal nutrition leads to impaired pancreatic beta-cell function which
      persists into adult life. Alone this is not sufficient to produce diabetes, but
      an inability to respond to a highly palatable fat diet may tip the balance
      towards impaired glucose tolerance.

PMID- 9246953
TI  - Onset and forces of term labor.

PMID- 9246954
TI  - Effect of nitric oxide, prostacyclin, and thromboxane on the vasospastic action
      of hydrogen peroxide on human umbilical artery.
AB  - BACKGROUND: The effect of hydrogen peroxide (H2O2) on vascular tone in the human
      umbilical artery was investigated to determine the mechanism of vasospasm in
      preeclampsia. METHODS: Helical sections of the umbilical artery were obtained
      from healthy pregnant women who delivered between the 37th and 39th week of
      gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (PG
      F2 alpha) were measured (isometric mechanical activity). Segments were treated
      with H2O2 alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals
      (mannitol), an inhibitor of thromboxane synthesis (sodium ozagrel), and an
      inhibitor of nitric oxide synthesis (L-NG-monomethyl arginine, LNMA), or an
      inhibitor of prostacyclin synthesis (tranylcypromine, TCP). RESULTS: Vascular
      tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment
      with mannitol significantly suppressed the vasospastic effect of H2O2. Removal of
      the endothelium decreased the vascular tension induced by H2O2. Treatment with
      TCP and LNMA potentiated the vascular tension. Pretreatment with TCP and LNMA
      reduced the vasospastic action of H2O2, whereas pretreatment with sodium ozagrel
      did not. CONCLUSION: Vascular tension in human umbilical arteries was potentiated
      by H2O2, and may be mediated by a suppression of the activity of nitric oxide or
      of prostacyclin. A direct action of H2O2 on vascular smooth muscle may also be
      involved.

PMID- 9246955
TI  - Fetal fibronectin and microorganisms in vaginal fluid of women with complicated
      pregnancies.
AB  - OBJECTIVES: To determine vaginal fetal fibronectin in women with pregnancies
      complicated by preterm labor (PTL), preterm premature rupture of the membranes
      (PPROM) or bleeding; to investigate possible relationships to the vaginal
      microflora; and to assess the ability to predict preterm delivery from these
      measures. MATERIAL AND METHODS: Group comparative study between women of the same
      gestational age with a normal pregnancy (n = 28) and consecutive women admitted
      with PTL (n = 63), PPROM (n = 18) and bleeding (n = 21). Samples of vaginal fluid
      were collected at the time of admission in complicated pregnancies and from the
      women with normal pregnancies. Fetal fibronectin was determined by enzyme
      immunoassay and quantitative aerobic and anaerobic microbiological cultures were
      performed. RESULTS: The number of positive (> or = 0.05 mg/L) vaginal fetal
      fibronectin values was higher among women with PTL, PPROM and bleeding compared
      to controls (p < 0.001). A positive fibronectin value was predictive of delivery
      < or = 34 weeks (sensitivity 64%, specificity 87%). The absence of hydrogen
      peroxide-producing lactobacilli was predictive for preterm delivery < 34 weeks
      (sensitivity of 100%, specificity 35%). CONCLUSIONS: The presence of vaginal
      fibronectin and the absence of hydrogen peroxide-producing lactobacilli was
      indicative of an increased risk for preterm delivery < 34 weeks.

PMID- 9246957
TI  - The relationship between umbilical artery Doppler findings, fetal biophysical
      score and placental inflammation in cases of premature rupture of membranes.
AB  - BACKGROUND: To assess the relationship between placental inflammation, umbilical
      artery Doppler waveforms and fetal biophysical profile score, umbilical artery
      Doppler studies and fetal biophysical evaluations were performed in 24 preterm
      pregnants with premature rupture of membranes (PPROM). SUBJECTS: After delivery,
      the placentas were microscopically examined and two subgroups were formed
      including noninflamed or inflamed placentas. RESULTS: In the first group, which
      includes 14 cases with no histological signs of placental inflammation, we found
      increased systolic/diastolic ratio only in one patient, whereas in the second
      group including ten cases with microscopically proven inflammation, nine were
      found to have increased systolic/diastolic ratios (p < 0.05). Mean
      systolic/diastolic ratio in the first and the second groups were 2.74 +/- 0.18
      and 4.64 +/- 0.93 respectively (p < 0.001). Mean biophysical profile score was 9
      +/- 1.04 in the first group and 7 +/- 1.05 in the second group (p < 0.001).
      CONCLUSION: Abnormal biophysical profile scores along with increased arterial
      systolic/diastolic ratios have been shown to be the markers of impending clinical
      infection.

PMID- 9246956
TI  - Pyospermia and preterm, prelabor, rupture of membranes.
AB  - OBJECTIVES: To investigate the possible association between presence of
      clinically unrecognized, specific genito-urinary tract microorganisms in men and
      preterm, prelabor rupture of membranes (PPROM) in their spouses. STUDY DESIGN:
      Case control study. Eleven couples with PPROM were enrolled in the case group and
      18 couples with normal pregnancies in the control group. For each man, samples of
      urine and semen were collected and a urethra swab was obtained. Microbiological
      assessment included, for each woman, cultures from vagina/cervix, urine and
      placenta. A smear from the vagina was obtained. RESULTS: In the case group,
      pyospermia was found in three men. Two of these men, as well as their spouses,
      were Chlamydia trachomatis positive, and in the third man no microorganisms could
      be detected. None of the controls had pyospermia (p = 0.045). Among the eight
      cases without pyospermia one man and one women with Chlamydia trachomatis was
      found, but their spouses were negative. In the control group, no Chlamydia
      trachomatis was detected (p = 0.014). Among the women two cases and one control
      had positive culture of Group B streptococci (NS). CONCLUSION: We suggest that
      the genital microflora of the man is associated with PPROM.

PMID- 9246958
TI  - Comparative study of three vaginal markers of the premature rupture of membranes.
      Insulin like growth factor binding protein 1 diamine-oxidase pH.
AB  - OBJECTIVE: To assess the diagnostic value of three vaginal markers-insulin-like
      growth factor binding protein 1 (= IGFBP1), diamine-oxidase (= DAO) and pH-for
      diagnosis of the premature rupture of membranes. STUDY: One hundred pregnant
      women participated in the study. They were divided into three groups: group A (34
      cases with intact membranes), group B (35 cases with total rupture of the
      membranes), group C (31 cases of suspected rupture of the membranes). Each
      patient underwent three successive tests for each of the three markers. The test
      order was allocated at random. For pH the reaction is colorimetric, for DAO the
      reaction is radio-enzymatic and for IGFBP1 the reaction is immuno
      chromatographic. All three reactions are qualitative in nature. The parameters
      studied were conventional statistical parameters (sensitivity = SN, specificity =
      SP, positive predictive value = PPV and negative predictive value = NPV).
      RESULTS: The analysis of the statistics gave the following results in percentages
      for SN, SP, PPV and NPV respectively; pH: 90.7%, 77.2%, 75%, 91.7%. DAO: 83.7%,
      100%, 100%, 89%. IGFBP1: 95.3%, 98.2%, 97.6%, 96.5%. CONCLUSION: The
      determination of variations in pH is not satisfactory. IGFBP1 is at least better
      than DAO with, additionally, advantages of rapidity and simplicity.

PMID- 9246960
TI  - A study on prophylactic antibiotics in cesarean sections--is it worthwhile?
AB  - BACKGROUND: To study the effect of single-dose prophylactic Augmentin on patients
      undergoing cesarean section. METHODS AND MATERIAL: Three hundred and twenty women
      undergoing cesarean section were randomized into two groups in a prospective,
      double-blind, placebo-controlled study. One hundred and sixty women were
      allocated to receive a single-dose of 1.2 g Augmentin at induction of anesthesia
      and 160 were allocated to a control group who received placebo. The following
      post-cesarean outcome parameters were compared between the two groups: duration
      of hospital stay, febrile morbidity, urine microscopy, bacteriuria, endometritis,
      and wound infection. RESULTS: There was no significant difference between the two
      groups with respect to the duration of post-operative hospital stay or the
      incidence of febrile morbidity, endometritis, and wound infection. However, the
      study group had fewer post-operative abnormalities in urine microscopy (p < 0.05)
      and bacteriuria (p < 0.01). The bacterial flora were also different between the
      two groups. CONCLUSION: Single-dose prophylactic Augmentin did not produce any
      clinically significant improvement in the post-operative course of patients
      undergoing cesarean section. If proper surgical techniques are followed in
      association with closed rectus sheath drainage, it is unlikely that any trial of
      antibiotics will be able to demonstrate any clinically significant outcome.

PMID- 9246959
TI  - Markers of intravascular coagulation and fibrinolysis in preeclampsia:
      association with intrauterine growth retardation.
AB  - BACKGROUND: Alterations in blood coagulation and fibrinolysis are believed to
      play an important role in the pathogenesis of preeclampsia. Hypercoagulability
      may be associated with features seen in preeclampsia, such as fibrin deposition
      in various organs, consumptive thrombocytopenia, and placental hypoperfusion,
      insufficiency and infarction. METHODS: In this cohort study, we compared the
      plasma levels of markers of blood coagulation and fibrinolysis in preeclamptic
      women to normotensive, pregnant controls. We also studied the association between
      these markers and intrauterine growth retardation (IUGR). RESULTS: In both mild
      and severe preeclampsia, the mean plasma concentrations of thrombin-antithrombin
      III complex (TAT) and plasminogen activator inhibitor type 1 (PAI-1) activity
      were significantly increased, while fibrinogen, antithrombin III (ATIII) and
      plasminogen activator inhibitor type-2 (PAI-2) antigen levels were significantly
      reduced compared to controls. Plasma D-dimer concentration was significantly
      higher in severe, but not in mild preeclampsia compared to the controls. The
      plasma level of fibrin monomer was similar in patients and controls. Patients
      with preeclampsia delivering growth retarded infants had significantly lower PAI
      1 activity and PAI-2 antigen concentrations in plasma than the remaining
      preeclamptic women. CONCLUSION: We found evidence of increased intravascular
      coagulation and fibrin turnover in preeclampsia. Low PAI-2 antigen plasma levels
      were associated with severe preeclampsia and IUGR.

PMID- 9246961
TI  - Superovulation combined with insemination or timed intercourse in the treatment
      of couples with unexplained infertility and minimal endometriosis.
AB  - BACKGROUND: To compare intrauterine insemination (IUI), direct intraperitoneal
      insemination (DIPI), and timed-intercourse (TI), each combined with
      superovulation, in the treatment of couples with unexplained infertility,
      including couples with minimal endometriosis. METHODS: A retrospective analysis
      of 233 superovulation cycles in 70 couples with unexplained infertility or
      minimal endometriosis. Stimulation protocol, pregnancy rate, pregnancy outcome,
      and complications of treatment were analyzed. RESULTS: The pregnancy rare was
      8.6% per cycle and 28.5% per couple. A majority of all treatment pregnancies
      (85%) occurred during the first four cycles of treatment. The duration of
      infertility did not influence the pregnancy rate. The pregnancy rate in patients
      with unexplained infertility was higher, but not significantly, than in patients
      with minimal endometriosis (27.7% versus 18.4%). No predictive marker for
      successful stimulation was found, except for the higher luteal progesterone level
      in cycles resulting in pregnancy. The multiple pregnancy rate was high: 30% of
      all pregnancies and 40% of all deliveries were multiple. CONCLUSIONS:
      Superovulation in combination with insemination or intercourse is effective and
      is still recommended in the treatment of couples with unexplained infertility.

PMID- 9246962
TI  - In vitro fertilization following laparoscopic ovarian diathermy in patients with
      polycystic ovarian syndrome.
AB  - BACKGROUND: To evaluate the in vitro fertilization outcome in patients with
      polycystic ovarian syndrome previously treated by laparoscopic ovarian diathermy.
      METHODS: We designed a prospective study to compare in vitro fertilization
      stimulation parameters and pregnancy rate for two groups of women with polycystic
      ovarian syndrome. In the first group, we included 23 patients previously treated
      by laparoscopic ovarian electrodiathermy (group A), in the second group we
      included 36 women who did not undergo surgical treatment (group B). All patients
      underwent the same ovarian hyperstimulation protocol and a standard in vitro
      fertilization and embryo transfer technique. In a limited number of women (five
      in group A and eight in group B) we measured the levels of sex steroids in
      follicular fluid. Statistical analysis was performed by means of chi-square test
      or Fisher's exact test to compare frequencies and by means of the Student's t
      test or ANOVA test to compare means. Significance was set at p < 0.05. RESULTS:
      In group A we found a significantly higher ongoing pregnancy rate (28.6% in group
      A vs 7.3% in group B), a significantly lower estradiol peak level (1722.73 +/-
      522.24 in group A vs 2314.48 +/- 692.60 in group B), a trend for lower abortion
      rates and an improvement in the number of patients administered human chorionic
      gonadotropin than in group B. The levels of estradiol, testosterone and
      androstenedione in follicular fluid were significantly lower from small to
      intermediate and to large follicles in group A, while in group B only estradiol
      and androstenedione were different. Lower levels of androstenedione and
      testosterone were found in each follicular pool of group A, compared to the
      respective pool in group B. CONCLUSION: We report a significantly better ongoing
      pregnancy rate after in vitro fertilization and embryo transfer procedures in
      women pretreated by means of laparoscopic ovarian electrocautery. These results
      may be related to lower androgen levels in the follicular fluid.

PMID- 9246963
TI  - Epidemiology of endometriosis in a Norwegian county.
AB  - OBJECTIVE: To estimate the prevalence and incidence of endometriosis in Norwegian
      women aged 40 to 42, and to evaluate reproductive events and life-style as risk
      factors for endometriosis as well as to evaluate related health-problems.
      MATERIAL AND METHODS: The study was performed partly as a cross-sectional study
      to estimate occurrence of endometriosis, partly as a case-control study to look
      for factors associated with endometriosis. The study group consisted of all
      female inhabitants--born 1950 to 1952--living in the county of Sor-Trondelag. In
      connection with a cardiovascular screening program information about reproductive
      events and gynecological problems including endometriosis and infertility was
      obtained. RESULTS: Totally 5139 women were asked to participate, and a
      questionnaire was completed by 4034 (78.5%). Endometriosis was reported by 2.0%
      of the women. Life-time risk for endometriosis was estimated to 2.2%. The annual
      incidence of new cases of endometriosis in this age group is less than 0.3%.
      There was a significant association between endometriosis and menarche before age
      13, and frequent menstrual periods. Nulliparity was more common in women with
      endometriosis as were infertility problems and pelvic pain. No significant
      association was found between endometriosis and exercise, smoking, body mass
      index and education. There was a high risk for women with endometriosis having
      had cervical conization or gynecological laparotomies such as infertility
      surgery, operations on ovaries as well as hysterectomies. CONCLUSION: In Sor
      Trondelag county the prevalence of endometriosis is 2.0% and the annual incidence
      is less than 0.3% for women in their early forties. A woman's life-time risk for
      endometriosis might be 2.2%. Early menarche, frequent menstruations, pelvic pain,
      infertility and nulliparity are associated with endometriosis.

PMID- 9246964
TI  - Ovarian cysts and cyclic hormone replacement therapy: is there an association?
AB  - OBJECTIVES: To evaluate whether there may be an association between
      postmenopausal ovarian cysts and hormone replacement therapy. METHODS: The study
      comprised 564 consecutive, asymptomatic, postmenopausal women who were referred
      for routine, transvaginal ultrasound examinations between January 1 and December
      31, 1995. Various demographic and ultrasonographic parameters were recorded on a
      prospectively-created, computerized data base. RESULTS: There was no difference
      in the prevalence of ovarian cysts with or without hormone replacement therapy
      (10.5% vs. 12.5%, respectively). However, in the subgroup of early postmenopausal
      women (40-55 years), the use of hormone replacement therapy was associated with a
      significantly reduced prevalence of ovarian cysts (10.4% vs. 28.6%; p < 0.05).
      CONCLUSIONS: Hormone replacement therapy is associated with a reduced prevalence
      of ovarian cysts in early postmenopause.

PMID- 9246965
TI  - The female pelvic floor: a dome--not a basin.
AB  - BACKGROUND: Classically and based on necropsy observations, the muscles of the
      pelvic floor (the levator ani and coccygeus muscles) have been described as
      having the shape of a basin. In a previous study by Hugosson et al. (1991),
      magnetic resonance imaging revealed the dome shape of the pelvic floor in live
      subjects when muscular tonus is present. METHODS: The normal anatomy and the
      dynamic movements of the female pelvis were examined with magnetic resonance
      imaging including conventional and fast sequences. Six nulliparous and six parous
      healthy women without signs or symptoms of pelvic relaxation were studied in the
      supine position at rest, during voluntary pelvic contractions and during bearing
      down. RESULTS: The levator ani muscle was dome-shaped at rest. During voluntary
      pelvic contractions the muscle straightened, becoming more horizontal and during
      bearing down it descended, becoming basin-shaped. The width of the genital hiatus
      was the same in both groups at rest and it widened during bearing down in all but
      two 3-para women. The bladder base was lifted upward and forward during voluntary
      pelvic contractions but during bearing down it descended. The rectum at rest had
      a posterior angle which decreased during voluntary pelvic contractions and
      increased during bearing down. CONCLUSIONS: MRI of the female pelvis is valuable
      in anatomic and dynamic analysis in healthy women and offers new information
      about the female pelvic floor. The female pelvic floor is shaped like a dome-not
      like a basin.

PMID- 9246966
TI  - Agreement between two successive transvaginal salpingosonography assessments of
      tubal patency.
AB  - OBJECTIVE: To evaluate the agreement between repeat transvaginal sonographic
      assessments of tubal patency using a combination of air and saline. MATERIAL AND
      METHODS: Twenty-nine patients were examined twice by the same investigator
      (H.S.). There was a three-month interval between the observations, and the
      investigator was blinded to the results of the first examination. Each patient
      was evaluated using three categories classified as: 1) bilateral patency, 2)
      unilateral patency and 3) bilateral occlusion. In addition, the pooled data from
      individual tubes was examined with respect to the detection of patency or
      occlusion. Data from the right and left tubes were analyzed separately as well.
      Agreement between the two examinations was subsequently determined using Cohen's
      kappa coefficient (kappa). When there were more than two categories, a weighted
      kappa coefficient was used. RESULTS: There was good (kappa = 0.61) agreement
      between the two examinations when each patient was evaluated individually. For
      the pooled data of all tubes (n = 46), the kappa coefficient was 0.53, but
      increased to 0.66 after correction for prevalence. There was no systematic bias
      between the successive examinations of tubes. There was more consistency between
      repeated observations in the right (kappa = 0.70) than in the left (kappa = 0.37)
      tubes. The prevalence of occlusion was higher in the left tubes. CONCLUSION:
      Transvaginal salpingosonography was shown to be a reliable method for the
      assessment of tubal patency.

PMID- 9246967
TI  - Prospective comparison of laparoscopic and traditional colposuspensions in the
      treatment of genuine stress incontinence.
AB  - OBJECTIVE: To compare prospectively the results of laparoscopic and traditional
      colposuspensions in the treatment of genuine stress incontinence and to evaluate
      the efficacy, technique, and functional and anatomical changes after these two
      procedures. MATERIALS AND METHODS: Ninety-two patients with urodynamically proven
      genuine stress incontinence participated in this study, with 46 patients randomly
      allocated to laparoscopic colposuspension, and the other 46 patients to the
      traditional procedures. All patients had repeat studies at least 3 months after
      operation. RESULTS: The bladder neck position was significantly elevated after
      operation either at rest or during straining in both groups (all p < 0.001), but
      it was higher in the traditional group than the laparoscopy group during
      straining (p < 0.05). Comparison of urodynamics before and after operation in
      both groups showed significantly increased minimal urethral resistance and
      improved pressure transmission ratios at the proximal urethra (Q2). The blood
      loss was less in the laparoscopy group. The duration of bladder drainage after
      laparoscopic colposuspension was shorter, and was not affected by subsequent
      laparotomy. The operative time was almost the same. The success rate of the
      laparoscopy group was lower than that of the traditional group (80.4% vs. 95.6%,
      p = 0.044). The complication rates were 10.8% and 17.4% respectively. CONCLUSION:
      Laparoscopic colposuspension is an effective method for the treatment of GSI, as
      documented by anatomical and functional assessments. However, the success rate is
      still lower than for the traditional procedure.

PMID- 9246968
TI  - Carcinoma of the uterine cervix in pregnancy. A study of the incidence and
      treatment in the western region of Sweden 1973 to 1992.
AB  - OBJECTIVE: To review the incidence, treatment and outcome of cervical cancer
      during pregnancy in the Western region of Sweden. METHODS: Population based data
      on cervical cancer during pregnancy were collected from 1973 to 1992. RESULTS:
      Cervical carcinoma was diagnosed in 33 women in association with pregnancy,
      giving an incidence of 11.1 cases per 100,000 deliveries and 7.5 cases per
      100,000 pregnancies. Pregnancy complicated one of every 55 cases of invasive
      carcinoma. Twelve women were in the 3rd trimester and nine women were post
      partum. Abnormal bleeding was the symptom that led to examination and diagnosis
      in 54.5% of the women and 45.5% of the women were asymptomatic but had an
      abnormal cervico-vaginal cytological test (39.4%) or abnormal finding at vaginal
      examination (6.1%) in association with pregnancy. In the 1st-2nd trimester all
      but one woman and in the 3rd trimester all but two women, had a stage I
      carcinoma. Post partum five women were in stage I, three women were in stage II
      and one woman had a stage III carcinoma. Histology revealed squamous cell
      carcinoma in 29 women, adenocarcinoma in three women and adenosquamous carcinoma
      in one woman. During the follow up period 1/12 women in the 1st trimester, 4/12
      in the 3rd trimester and 2/9 women post partum have died of disease. CONCLUSION:
      During the years of this study different modalities of treatment were used, with
      a change from primary radiation to primary surgery.

PMID- 9246969
TI  - Cisplatin-induced nephrotoxicity and the protective effect of fosfomycin on it as
      demonstrated by using a crossover study of urinary metabolite levels.
AB  - BACKGROUND: Cisplatin induces nephrotoxicity and this study evaluated the
      protective effect of fosfomycin on it in 11 gynecological cancer patients.
      METHODS: The N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin (beta
      2MG), creatinine (uCr) and total protein (TP) levels in a 24-hour urine specimen
      as well as the blood urea nitrogen (BUN) and serum creatinine (sCr) were measured
      before and after CAPF chemotherapy alone (control) or with fosfomycin. RESULTS:
      The results were statistically analyzed by using the t-test. NAG, beta 2MG, uCr
      and TP levels increased significantly after chemotherapy in the control patients,
      but BUN and sCr levels did not change significantly. The NAG level in the control
      group was twice as high as in the fosfomycin group 8 days after chemotherapy (p <
      0.01). The uCr and TP in control patients increased significantly after
      chemotherapy when compared to those in patients coad-ministered fosfomycin. There
      were no significant changes in beta 2MG, BUN and sCr levels. CONCLUSIONS:
      Cisplatin affected the levels of NAG, beta 2MG, uCr and TP without influencing
      BUN and sCr levels. Fosfomycin, therefore, may be useful as a supplemental
      treatment for reducing cisplatin nephrotoxicity, especially proximal tubular
      damage.

PMID- 9246971
TI  - Can women with intrapartum rupture of anal sphincter still suffer after-effects
      two decades later?
AB  - BACKGROUND: Recent research has revealed that women who suffer anal sphincter
      rupture (ASR) during delivery can experience persisting complaints some time
      afterwards. Examinations have been made some years postpartum, but it would be of
      interest to know if women with anal sphincter rupture might still have complaints
      attributable to the tear, two decades later. METHODS AND MATERIAL: A
      questionnaire was mailed to women with recorded intrapartum anal sphincter
      rupture (n = 66) and to matched controls without anal sphincter rupture (n = 66),
      two decades after the event. RESULTS: Forty-one of the anal sphincter rupture
      women and 38 controls replied. Anal problems were more often experienced by the
      anal sphincter rupture subjects (n = 18) than by the controls (n = 7) (P < 0.01).
      Complaints such as anal fissures, gas incontinence and leakage into lingerie were
      significantly more common in the sphincter rupture group. Four claimed the physic
      trauma had deterred them from further pregnancy; two had nevertheless given birth
      later on. Five (12%) of the women were unaware that they had sustained a
      sphincter tear. CONCLUSIONS: Women with intrapartum anal sphincter rupture can
      still suffer problems 20 years afterwards. In the follow-up of these women,
      information and support are essential and active tracing of such women is to be
      recommended.

PMID- 9246970
TI  - An economic evaluation of laparoscopy and open surgery in the treatment of tubal
      pregnancy.
AB  - BACKGROUND: Laparoscopy has generally replaced open surgery in the treatment of
      ectopic pregnancy. This study assesses the impact of the introduction of
      laparoscopy in the surgical treatment of tubal pregnancy on costs. METHODS:
      Consecutive patients undergoing primary surgery for tubal pregnancy between
      January 1992 and December 1995 were included in the study. Surgery was performed
      laparoscopically or by open surgery. Cost for each treatment was calculated by
      multiplying resources used with calculated resource unit prices. The analysis was
      stratified for radical and conservative surgery. RESULTS: Data of 255 patients
      were analysed. Tubal pregnancy was successfully treated in all patients. Costs
      per patient were US$ 3,490 for radical open surgery, US$ 1,872 for radical
      laparoscopic surgery, US$ 3420 for conservative open surgery and US$ 2,125 for
      conservative laparoscopic surgery. Differences in costs were caused by a
      decreased duration of hospital stay after laparoscopy, and, in case of
      conservative surgery, by an increased persistent trophoblast rate after
      laparoscopy. CONCLUSIONS: Laparoscopy is equally effective as open surgery in the
      treatment of tubal pregnancy, and considerably reduces costs.

PMID- 9246972
TI  - Conservative management of Sertoli-Leydig cell tumor of the ovary.

PMID- 9246973
TI  - Reappearance of cancer of the cervix 19 years after radiotherapy.

PMID- 9246974
TI  - Successful outcome in a pregnancy complicated by large hepatic hemangioma.

PMID- 9246975
TI  - A placebo-controlled trial of oral ergometrine to reduce postpartum hemorrhage.

PMID- 9246976
TI  - Long-term prediction of fetal weight; the proportional extrapolation method.

PMID- 9246977
TI  - Ethics in orthopedic research.

PMID- 9246978
TI  - Patient-related risk factors for early revision of total hip replacements. A
      population register-based case-control study of 674 revised hips.
AB  - In this population register-based, matched case-control study, we assessed
      patient-related factors and early risk of revision after total hip replacement
      (THR). Information was obtained via a mall survey among patients reported to the
      Norwegian Arthroplasty Register during the period 1987-1993. The study included
      674 revised hips, as cases, and 1,343 hips with a primary operation only, as
      controls. Completed questionnaires were received from 81% of the 2,017 individual
      cases and controls. We identified a set of patient-related factors associated
      with poor THR prognosis. Increasing weight was a risk factor among male patients
      older than 67 years who were more than 1.77 m tall (p = 0.01). Smoking had no
      overall effect, but former heavy smokers had an increased risk of 2.8 compared to
      never-smokers. Alcohol intake was associated with an increased risk of
      dislocation. Revision due to infection was commoner among patients taking anti
      diabetic drugs (OR = 14) than among patients taking no medication. An increased
      overall revision risk was found among patients using systemic steroids (OR = 2.8)
      or local pulmonary steroids (OR = 6.0). The risk also increased in male patients
      performing regular exercise before the primary operation (OR = 2.6), and in
      female patients of working-age doing heavy work (OR = 1.9).

PMID- 9246979
TI  - Lifestyle factors and hip arthrosis. A case referent study of body mass index,
      smoking and hormone therapy in 503 Swedish women.
AB  - We investigated in a case-referent study the relationship between arthrosis of
      the hip in women and lifestyle factors such as body mass index (BMI), smoking and
      hormone therapy. The study comprised all women of ages 50-70 years, living in 5
      counties and 5 towns in Sweden 1991-1994. The cases (n 230) were women with total
      hip replacements (THR) because of primary arthrosis, and the referents (n 273)
      were randomly selected women from the study base, without hip problems. All women
      were interviewed about height, weight, smoking habits, hormone therapy, sports
      activities, occupational history, home work, etc, to the age of 50. The relative
      risk of developing hip arthrosis leading to a THR after the age of 50 was
      associated with an increased BMI. The highest value, 2.9 (Cl 1.3-6.5), was
      reported in those with BMI > or = 25 at the age of 40. The preventive value of
      weight loss seems substantial. There was a greater risk of 1.5 (Cl 1.0-2.2) for
      smokers than for non-smokers. Use of contraceptive pills meant an increase in the
      relative risk for THR, unlike estrogen substitution which was associated with a
      lower risk than in unexposed persons.

PMID- 9246980
TI  - Local wound and systemic coagulation/fibrinolysis responses in hip arthroplasty.
      Influence of allogeneic and autologous blood transfusion.
AB  - 22 patients undergoing elective hip arthroplasty were studied. In 12 patients, a
      closed-loop autotransfusion system, without anticoagulant, was used and 10 had an
      ordinary wound drainage allowing repeated blood sampling from the wound. Plasma
      concentrations of antithrombin (AT), fibrin, soluble (SF) and fibrin D-dimer were
      determined preoperatively, 3, 8, and 24 hours after starting surgery. Wound
      drainage blood had increased concentrations of SF and fibrin D-dimer and
      decreased concentrations of AT compared to reference values and systemic
      concentrations in patients. Plasma concentrations of SF, fibrin D-dimer and AT
      did not differ between patients receiving retrieved blood and those receiving
      stored red blood cell concentrates (RBCs). Patients receiving blood transfusions
      had lower AT concentrations at 8 hours after starting surgery than those not
      receiving such a transfusion.

PMID- 9246982
TI  - Intracapsular pressure and loosening of hip prostheses. Preoperative measurements
      in 18 hips.
AB  - We measured the intracapsular pressure preoperatively in 18 hips (17 patients)
      before revision of a total hip arthroplasty because of aseptic loosening.
      Distension of the joint capsule was measured with sonography in 13 cases. In
      extension, the mean intracapsular pressure was 26 (0-60) mmHg, in extension and
      inward rotation it was 159 (24-280) mmHg, in extension and outward rotation it
      was 30 (3-67) mmHg and in 45 degrees of flexion it was 12 (0-28) mmHg. A mean of
      6 (0.5-20) mL of joint fluid was aspirated after the pressure measurements.
      Sonography showed increased joint fluid/synovial edema and/or increased capsular
      thickness, as compared to 34 unrevised, radiographically not loose prosthetic
      hips, and that the capsular distension correlated to intracapsular pressure
      during extension and inward rotation. We conclude that the intracapsular pressure
      usually is elevated in a hip joint with loose prosthetic components, that the
      intracapsular pressure varies with the position of the hip and that capsular
      distension reflects increased intracapsular pressure. The increased and often
      very high pressure, varying during gait, may pump debris away from the joint
      along the interfaces and even by itself cause osteolysis and loosening.

PMID- 9246981
TI  - Autotransfusion--bacterial contamination during hip arthroplasty and efficacy of
      cefuroxime prophylaxis. A randomized controlled study of 40 patients.
AB  - 40 patients undergoing primary hip arthroplasty, given autologous processed blood
      transfusion, were randomized a receive no antibiotic prophylaxis (group A, n 20)
      or cefuroxime (1.5 g single injection; group B, n 20). Bacterial contamination at
      various steps in the autotransfusion procedure was assessed in liquid and solid
      culture media. The operation field and the wound drainage blood were never
      contaminated either of the groups but some of the suction tips were. Parts of the
      Vacufix blood collection bags of group A contained bacteria, but none in group B.
      Processed red blood cell concentrates in both groups showed bacterial growth.
      Greater blood loss did not increase the contamination rate in general. Isolated
      bacteria included the species Staphylococcus epidermidis, coagulase-negative
      staphylococci and Propionibacteria in both groups, but with different cell
      counts. In addition, Corynebacterium bovis et minutissimum and Moraxelle were
      identified in group A. In conclusion, autologous blood transfusion was a safe
      procedure. If contamination occurred, the bacterial count was low, and the
      bacteria of low pathogenicity. Antibiotic prophylaxis with cefuroxime reduced
      this contamination of suction tips and collection bags and limited the transfer
      of autologous blood products.

PMID- 9246983
TI  - Outcome after transphyseal hip fractures. 4 children followed 34-48 years.
AB  - We report long-term outcomes in 4 patients with transphyseal fractures of the
      hip, a rare injury. All the patients were treated without surgery. The results
      were good in all the patients at follow-up, 34-48 years after injury. The only
      complication we found was a leg-length discrepancy of 3 cm in 1 patient due to
      premature closure of the capital femoral physis.

PMID- 9246984
TI  - Poor reproducibility of classification of proximal humeral fractures. Additional
      CT of minor value.
AB  - Fractures of the proximal humerus can be described using the Neer and AO fracture
      classifications. To assess the reproducibility and reliability of these
      classifications, we investigated 26 proximal humeral fractures with both plain
      radiographs and CT. 5 specialists in orthopedic surgery and 5 specialists in
      radiology independently classified all radiographs on 2 occasions. There was a
      moderate agreement between the observers when using the Neer classification, but
      only a fair agreement with the AO classification. The Neer system had a kappa
      value of 0.42 and the AO had a value of 0.31 in the first assessment. In the
      second assessment the kappa values were 0.45 and 0.30, respectively.
      Intraobserver reproducibility was slight to almost perfect agreement with Neer
      (kappa range 0.20-0.85) and slight to moderate agreement with AO (kappa range
      0.16-0.60). The observers most familiar with shoulder fracture radiographs and
      shoulder fracture treatment were more consistent in their classifications. We
      conclude that even with CT, the fracture classifications of Neer and AO have a
      low consistency. Neither classification system is reproducible enough to allow
      comparisons of different studies.

PMID- 9246985
TI  - Shoulder hemiarthroplasty in rheumatoid arthritis. 19 cases reexamined after 1-17
      years.
AB  - We reexamined 19 shoulder hemiarthroplasties in patients with rheumatoid
      arthritis after a mean of 8 (1-17) years. For the evaluation, we used the
      Constant and Murley score and routine radiographs. At the follow-up examination,
      12 of the 19 shoulders showed little, if any, pain. In 7 shoulders the pain was
      moderate and no patient had severe pain. The range of motion was not improved. In
      7/18 shoulders proximal subluxation of the head of the humeral prosthesis and in
      9/15 shoulders, progression of the glenoid erosion were seen. The increase in
      glenoid erosion and the postoperative pain were not correlated. Hemiarthroplasty
      of the shoulder effectively relieves the pain in rheumatoid patients and this
      seems long-lasting.

PMID- 9246986
TI  - Bone-ligament transfer of coracoacromial ligament for acromioclavicular
      dislocation. A new fixation method used in 6 cases.
AB  - We treated 6 grade III acromioclavicular injuries with a new fixation method
      using a bone-ligament transfer of the coracoacromial ligament into a clavicular
      tunnel. After an average of 16 months, function and cosmesis were excellent in
      all patients.

PMID- 9246987
TI  - Sarcomere length in wrist extensor muscles. Changes may provide insights into the
      etiology of chronic lateral epicondylitis.
AB  - Since the etiology of tennis elbow (lateral epicondylitis) is poorly understood,
      we studied the anatomical changes in the extensor carpl radialis brevis (ECRB)
      muscle during elbow joint rotation. Specifically, we measured ECRB sarcomere
      length, using an intraoperative laser diffraction procedure that measures muscle
      sarcomere length with an accuracy of +/- 0.05 micron. We found an unexpected
      biphasic response in ECRB sarcomere length as the elbow was rotated from full
      extension to full flexion. The initial sarcomere length of 3.49 microns, with the
      elbow extended, was gradually changed to 3.68 microns, 3.34 microns, 3.81
      microns, and 3.45 microns with progressive elbow flexion. Based on the very
      nonlinear mechanical properties of skeletal muscle, this "double lengthening" of
      the ECRB during progressive flexion would impose intense eccentric contractions
      on the muscle itself. Given that eccentric contractions cause muscle injury and
      subsequent inflammation, these findings may provide insights into the etiology of
      lateral epicondylitis.

PMID- 9246988
TI  - External fixation versus percutaneous pinning for unstable Colles' fracture.
      Equal outcome in a randomized study of 60 patients.
AB  - 60 patients > 20 years of age, with comminuted distal radial fractures of type
      Older 3 or 4, were randomly allocated to two treatment groups: external fixation
      a.m. Hoffmann or percutaneous Kirschner wire pinning combined with immobilization
      in a plaster cast. The groups were similar in age, gender, fracture type and
      dislocation. All patients were immobilized for 6 weeks and the outcome was
      assessed after 6 months. The groups showed similar results with respect to
      radiographic parameters and function. All fractures healed and no difference in
      complication rate was observed. We conclude that most unstable distal radial
      fractures, classified as Older's type 3 and 4, can be treated with percutaneous
      pinning and a plaster cast, which is simpler and cheaper than external fixation.

PMID- 9246989
TI  - K-wire fixation for redislocated Colles' fractures. Malunion in 8/21 cases.
AB  - One therapeutic alternative for redislocation of Colles' fractures is closed
      reduction and transstyloid Kirschner-wire fixation. We describe our results
      concerning 21 redislocations treated in this way. According to Older's
      classification, B fractures were type 3 and 13 fractures type 4. After a median
      follow-up period of 2 years, most patients had regained normal volar tilt, but
      significant loss of radial tilt and radial length was found in 11 patients.
      Malunion occurred in 8 wrists due to either fracture comminution or insufficient
      K-wire fixation. According to Gartland and Werley's point system, the end-results
      were poor in 2, fair in 11, good in 4, and excellent in 4 wrists. There was no
      statistically significant difference in secondary displacement and functional end
      result between Older's type 3 and type 4 fractures. We conclude that K-wire
      fixation is frequently not firm enough and external fixation might be a better
      alternative for stabilizing redislocated distal radial fractures.

PMID- 9246990
TI  - Longitudinal growth rate following slow physeal distraction. The proximal tibial
      growth plate studied in rabbits.
AB  - Studies in animals by de Bastiani et al. (1986) on leg lengthening by physeal
      (growth plate) distraction have shown that the integrity of the growth plate can
      be preserved intact if slow rates of distraction are employed. Clinically,
      however, this technique has been restricted to the period shortly before skeletal
      maturity, due to uncertainty about the behavior of the growth plate following
      distraction. We conducted 2 studies. 11 immature rabbits used in a study on the
      normal growth at the proximal tibial physis established that the growth rate was
      unchanged with transfixing K-wires in the epiphysis. The normal growth rate of
      the proximal physis of the tibia decreased with age and was expressed as a
      quadratic function, Gn (mm/day) = 0.44-0.002 age (days). At 6 weeks of age, the
      growth rate was 0.33 mm/day, slowly decelerating to a rate of 0.15 mm/ day by the
      16th week. In the lengthening study, to determine whether the growth plate would
      maintain a normal rate of growth following slow distraction, a custom-made
      bilateral distraction device was applied to the proximal tibial epiphysis of 32
      immature rabbits aged 6 weeks and weighing approximately 500 gm. The growth
      behavior of the growth plate following 2, 3 and 4 weeks of distraction was
      studied. The rate of distraction was set at 0.5 mm/ day. The mean amount of
      distraction achieved was 8.5 mm, 11.3 mm and 14.6 mm resulting in a mean 'net'
      increase in length as compared to the experimental control after the distractor
      was removed amounting to 3.0 mm (55% of the control growth), 3.6 mm (47%) and 4.2
      mm (40%), respectively. Subsequent serial measurements, up to 13 weeks
      postdistraction, showed no significant change in the discrepancy between the
      length of the tibia and the growth rate at the proximal tibial epiphysis and
      between the distracted and the contralateral controls in all 3 groups. Our
      findings suggest that the proximal tibial growth plate in the rabbit would
      maintain a normal growth rate after slow physeal distraction for periods up to 4
      weeks.

PMID- 9246991
TI  - AP-translation in the proximal disc adjacent to lumbar spine fusion. A
      retrospective comparison of mono- and polysegmental fusion in 120 patients.
AB  - 120 consecutive patients with painful spondylolisthesis underwent combined
      anterior and posterior fusion. Patients were divided retrospectively into two
      groups. In group I, 46 patients were treated with monosegmental fusion. In group
      II, 74 had polysegmental fusion. The mean follow-up time was 3 (2-7) years.
      Anterior posterior (AP)-translation in the first disc superior to fusion was
      measured according to Wiltse and Winter (1983). In group I, 3 and in group II, 10
      patients developed an AP-translation of more then 3 mm in the disc adjacent to
      the fusion. AP-translation correlated with the number of fused segments and the
      follow-up time.

PMID- 9246992
TI  - Trunk rotation in scoliosis. The influence of curve type and direction in 150
      children.
AB  - We compared the angle of trunk rotation (ATR) from scoliometer readings with Cobb
      angle measurements of the lateral deviation of the spine in 150 children referred
      to hospital for evaluation of scoliosis. The mean Cobb angle in thoracic curves
      was 16 degrees. In thoracolumbar curves 17 degrees and in lumbar curves 20
      degrees. In thoracic curves and in right convex curves no patient with a Cobb
      angle of 25 degrees or more had an ATR below 9 degrees. In thoracolumbar and
      lumbar and in left convex curves, 7 degrees ATR was occasionally associated with
      scoliosis of 25 degrees or more. The correlation coefficient between the ATR and
      Cobb angle in right convex curves was 0.65 compared to 0.57 in left convex
      curves. We conclude that a criterion of > 7 degrees ATR for thoracic or right
      convex curves and one of > 6 degrees ATR for thoracolumbar and lumbar or left
      convex curves seem adequate for identification of patients with Cobb angles of 25
      degrees or more, which reduces the need for spinal radiography and follow-up
      outside the school screening programs.

PMID- 9246993
TI  - MRI preferable to diagnostic arthroscopy in knee joint injuries. A double-blind
      comparison of 47 patients.
AB  - We compared the findings of low-field MRI of the knee with those of subsequent
      arthroscopy. In a double-blind set-up, 47 patients with knee joint injuries were
      enrolled. Two radiologists independently interpreted the MRI examinations and
      consensus was obtained in case of discrepancy. Arthroscopy was performed without
      knowledge of the MRI findings. The accuracy rates of MRI for evaluating the
      medial meniscus, lateral meniscus and anterior cruciate ligament were 77%, 91%
      and 96%, respectively, when arthroscopy was considered the "golden standard".
      When MRI was considered the standard, the figures for arthroscopy were 74%, 91%
      and 96%. MRI found the indication for treatment in 18 of 21 patients who were
      treated at the arthroscopy. In 17 patients, neither MRI nor arthroscopy detected
      any lesion. In the remaining 9 patients, MRI demonstrated a lesion, but no lesion
      was found at the subsequent arthroscopy. Our conclusion is that low-field MRI can
      be used as a first-line diagnostic examination in patients with suspected
      meniscus or cruciate ligament injuries and thus a substantial number of negative
      diagnostic arthroscopies can be avoided.

PMID- 9246994
TI  - Dislocation of total knee arthroplasty. A report of 6 cases with 2 patterns of
      instability.
AB  - We report 6 cases of dislocation of total knee arthroplasty (TKA). We identified
      2 patterns of instability in the sagittal plane, one with posterior translation
      of the tibia, occurring mainly in the postoperative period and usually resulting
      from a trauma, and the other with anterior translation of the tibia, occurring 6
      months to 7 years postoperatively and with no preceding trauma. In the latter
      group, instability was manifested gradually as a lengthening of the posterior
      cruciate ligament and the posterior capsule, leading to a recurvatum deformity of
      the knee.

PMID- 9246995
TI  - Diagnosis of lateral ankle ligament injuries. Comparison between talar tilt, MRI
      and operative findings in 112 athletes.
AB  - We evaluated the reliability of the radiographic talar tilt test by MRI
      examinations in 112 athletes with injuries to the lateral ligaments of the ankle.
      25 athletes with a talar tilt > 15 degrees were treated operatively.
      Intraoperative findings and the talar tilt test were compared with MR imaging
      results. Our results suggest that MRI is a reliable method for diagnosing
      injuries of the lateral ankle ligaments. The talar tilt test cannot evaluate the
      specific pathology of lateral ankle ligaments, but it was reliable in indicating
      complete double-ligament ruptures (anterior talofibular and calcaneo-fibular
      ligaments), when talar tilt was 15 degrees or more than on the uninjured side.

PMID- 9246996
TI  - Minor amputations on the feet after revascularization for gangrene. A consecutive
      series of 95 limbs.
AB  - A consecutive series of 89 patients (95 limbs) with gangrene were operated on
      with amputation of toes or some distal part of the foot after arterial
      reconstruction. 43 patients had diabetes. Healing was achieved in 81/82 feet when
      the reconstruction was open. Amputation below or above the knee was required in
      4/5 limbs when the reconstruction failed. 8 patients died before healing. The
      median time to healing was 30 (17-452) days, after a single amputation, and 115
      (36-466) days, when more than one procedure had been necessary. We concluded that
      amputations on the feet for gangrene usually heal after arterial reconstruction,
      in patients with diabetes as well as in those with arteriosclerosis. No weight
      bearing and control of infection are important during the early postoperative
      period.

PMID- 9246997
TI  - The radiographic stage of giant cell tumor related to stromal cells'
      proliferation. Tissue cultures in 13 cases.
AB  - The clinical behavior of giant cell tumor is related to the radiological
      appearance. To test the hypothesis that in vitro proliferation of the neoplastic
      stromal cell population of giant cell tumors is related to the radiological
      appearance, this study was undertaken. A prospective analysis of the cells
      migrating from 13 consecutive tumors was conducted. Growth curves and population
      doubling-times (PDT) for first and fifth passages were calculated and alkaline
      phosphatase levels were measured and compared to preoperative radiographic
      staging. A strong negative correlation was found between PDT and the radiographic
      stage. Tumors in stages I and II (low aggressiveness) were found to have an
      average cell population doubling-time of 11 (SD 2.2) days, while those in stage
      III (high aggressiveness) showed a doubling-time of 6 (SD 2.2) days. Low alkaline
      phosphatase activity was noted in all cultures, a finding consistent with the
      putative preosteoblastic potential of these stromal cells. This putative origin
      is also indicated by the differentiation response to retinoic acid. The findings
      suggest that the in vitro proliferation of the mononuclear stromal cell
      population of giant cell tumors is related to the radiographic stage and may
      predict the clinical behavior of these tumors.

PMID- 9246998
TI  - Reconstruction of tibia by ipsilateral vascularized fibula and allograft. 12
      cases with malignant bone tumors.
AB  - We treated 12 patients with a primary sarcoma of the tibia by resection and
      centralization of the ipsilateral vascularized fibula with preserved
      vascularization. The reconstruction was combined with an allograft. The median
      bone defect after tumor resection was 14 (8-24) cm. The anastomosis between the
      allograft and the recipient bone was stabilized by a plate or screws or Kirschner
      wires. To reconstruct the soft tissues, 8 patients underwent a gastrocnemius
      plasty and 2 patients a free vascularized flap of the latissimus dorsi muscle.
      The mean follow-up period was 2.5 (2-3.5) years. 2 years after implantation,
      union > or = 75% of the anastomosis area was noted in 10 patients. A deformity or
      fracture of the distal junction occurred in 7 patients with a screw or Kirschner
      wire fixation. Neither deformity nor fracture developed in the 5 patients with
      plate-fixation.

PMID- 9246999
TI  - Ulnar nerve compression--a case of giant uremic tumoral calcinosis.

PMID- 9247000
TI  - Lipoma arborescens with osteochondral metaplasia--a case mimicking synovial
      osteochondromatosis in a lateral knee bursa.

PMID- 9247002
TI  - Congenital absence of fibulae, with equinovarus deformity--a case report.

PMID- 9247001
TI  - Candida arthritis after total knee arthroplasty--a case of successful treatment
      without prosthesis removal.

PMID- 9247003
TI  - Degenerative tear of the tibialis anterior tendon after corticosteroid injection-
      augmentation with the extensor hallucis longus tendon, case report.

PMID- 9247004
TI  - Invited commentary: on the role of ethics committees in epidemiology professional
      societies.

PMID- 9247005
TI  - Weight change and diabetes incidence: findings from a national cohort of US
      adults.
AB  - To examine how long-term patterns of weight change affect the risk for diabetes,
      especially non-insulin-dependent diabetes mellitus, the authors examined the
      relation of weight change over a period of about 10 years (from the baseline
      examination in 1971-1975 until the first follow-up examination in 1982-1984) to
      the 9-year incidence of diabetes mellitus (1984-1992) in a national cohort of
      8,545 US adults from the National Health and Nutrition Examination Survey
      Epidemiologic Followup Study. Diabetes incidence was identified from death
      certificates, hospitalization and nursing home records, and self-report. In this
      cohort, 487 participants developed diabetes. The hazard ratios were 2.11 (95%
      confidence interval (CI) 1.40-3.18) for participants who gained 5- < 8 kg, 1.19
      (95% CI 0.75-1.89) for participants who gained 8- < 11 kg, 2.57 (95% CI 1.84
      3.85) for participants who gained 11- < 20 kg, and 3.85 (95% CI 2.04-7.22) for
      participants who gained 20 kg or more compared with participants whose weights
      remained relatively stable. The authors found no evidence that the results
      differed by age, sex, or race. They estimated that the population attributable
      risk was 27% for weight increases of 5 kg or more. Results from this study and
      other recent studies suggest that the increase in body mass index in the United
      States that occurred during the 1980s may portend an increase in the incidence of
      non-insulin-dependent diabetes mellitus with important public health consequences
      in future years.

PMID- 9247006
TI  - Dietary flavonoids and the risk of lung cancer and other malignant neoplasms.
AB  - Flavonoids are effective antioxidants and, in theory, may provide protection
      against cancer, although direct human evidence of this is scarce. The relation
      between the intake of antioxidant flavonoids and subsequent risk of cancer was
      studied among 9,959 Finnish men and women aged 15-99 years and initially cancer
      free. Food consumption was estimated by the dietary history method, covering the
      total habitual diet during the previous year. During a follow-up in 1967-1991,
      997 cancer cases and 151 lung cancer cases were diagnosed. An inverse association
      was observed between the intake of flavonoids and incidence of all sites of
      cancer combined. The sex- and age-adjusted relative risk of all sites of cancer
      combined between the highest and lowest quartiles of flavonoid intake was 0.80
      (95% confidence interval 0.67-0.96). This association was mainly a result of lung
      cancer, which presented a corresponding relative risk of 0.54 (95% confidence
      interval 0.34-0.87). The association between flavonoid intake and lung cancer
      incidence was not due to the intake of antioxidant vitamins or other potential
      confounding factors, as adjustment for factors such as smoking and intakes of
      energy, vitamin E, vitamin C, and beta-carotene did not materially alter the
      results. The association was strongest in persons under 50 years of age and in
      nonsmokers with relative risks of 0.33 (95% confidence interval 0.15-0.77) and
      0.13 (95% confidence interval 0.03-0.58), respectively. Of the major dietary
      flavonoid sources, the consumption of apples showed an inverse association with
      lung cancer incidence, with a relative risk of 0.42 (95% confidence interval 0.23
      0.76) after adjustment for the intake of other fruits and vegetables. The results
      are in line with the hypothesis that flavonoid intake in some circumstances may
      be involved in the cancer process, resulting in lowered risks.

PMID- 9247007
TI  - Intake of vitamins E, C, and A and risk of lung cancer. The NHANES I
      epidemiologic followup study. First National Health and Nutrition Examination
      Survey.
AB  - The relation between the dietary intake of vitamins E, C, and A (estimated by a
      24-hour recall) and lung cancer incidence was examined in the First National
      Health and Nutrition Examination Survey Epidemiologic Followup Study cohort of
      3,968 men and 6,100 women, aged 25-74 years. During a median follow-up period of
      19 years (from 1971-1975 to 1992), 248 persons developed lung cancer. Adjusted
      for potential confounders using Cox proportional hazards regression methods with
      age as the underlying time variable, the relative risk of lung cancer for
      subjects in the highest quartile of vitamin C intake compared with those in the
      lowest quartile was 0.66 (95% confidence interval (CI) 0.45-0.96). For vitamin A
      intake, a protective effect was observed only for its fruit and vegetable
      component (carotenoids) among current smokers (relative risk = 0.49, 95% CI 0.29
      0.84), but this was modified by the intensity of smoking (a statistically
      significant effect (relative risk = 0.33, 95% CI 0.13-0.84) was observed only for
      those in the lowest tertile of pack-years of smoking). The vitamin E intake-lung
      cancer relation was modified by the intensity of smoking with a significant
      protective effect confined to current smokers in the lowest tertile of pack-years
      of smoking (relative risk = 0.36, 95% CI 0.16-0.83). Overall, there was no
      additional protective effect of supplements of vitamins E, C, and A beyond that
      provided through dietary intake. When vitamin E, vitamin C, and carotenoid
      intakes were examined in combination, a strong protective effect was observed for
      those in the highest compared with those in the lowest quartile of all three
      intakes (relative risk = 0.32, 95% CI 0.14-0.74). These data provide support for
      a protective role of dietary vitamins E and C and of carotenoids against lung
      cancer risk but with a modification in effects by the intensity of cigarette
      exposure. While smoking avoidance is the most important behavior to reduce lung
      cancer risk, the daily consumption of a variety of fruits and vegetables that
      provides a combination of these nutrients and other potential protective factors
      may offer the best dietary protection against lung cancer.

PMID- 9247008
TI  - Comparison of self-reported and database-linked family history of cancer data in
      a case-control study.
AB  - The authors linked interview data drawn from Utah participants in the Diet,
      Activity, and Reproduction in Colon Cancer (DARCC) Study (1992-1995) to
      genealogic and cancer information contained in the Utah Population Database
      (UPDB). They evaluated the sensitivity of subjects' reports of familial cancers
      and measured the overall agreement between reported and database records with the
      kappa (kappa) statistic. They calculated odds ratios from logistic regression to
      compare the relative risk estimates that would result from use of either data set
      (or both data sets). Overall, 37.6% (331 of 881) of the Utah DARCC subjects were
      linked to the UPDB genealogy. High sensitivities were observed for subjects'
      reports of breast (83%), colorectal (73%), and prostate (70%) cancers, while
      ovarian (60%) and uterine (30%) cancers were not reported as well. Results for
      kappa were similar, with values of 0.63 for breast cancer and 0.56 for colorectal
      cancer. Although the observed kappa s of 0.36 and 0.25 for ovarian and uterine
      cancers, respectively, exceeded chance expectations, the agreement between
      subjects' reports and database records was unimpressive. No consistent difference
      was observed between cases and controls in the accuracy of self-reports. In
      general, higher sensitivities were observed among younger subjects than older
      subjects; females reported family histories of cancer only slightly better than
      males. A college education was not consistently associated with more accurate
      reporting of family history of cancer. These results indicate that subjects in a
      case-control study are able to report accurately family histories of several
      common kinds of cancer and that they can do so without observable recall bias.
      The accuracy of self-reports may not be adequate for reproductive tract cancers
      and cancers such as rectal cancer that are frequently confused with cancers of
      similar organs.

PMID- 9247009
TI  - Sudden infant death syndrome and smoking in the United States and Sweden.
AB  - The association between sudden infant death syndrome (SIDS) and maternal smoking
      was compared between the United States and Sweden-two countries with different
      health care and social support programs and degrees of sociocultural
      heterogeneity. For 1990-1991 among the five US race/ethnic groups studied, SIDS
      rates ranged from a high of 3.0 infant deaths per 1,000 live births for American
      Indians to a low of 0.8 for Hispanics and Asian and Pacific Islanders. The SIDS
      rate for Sweden (using 1983-1992 data) was 0.9. The strong association between
      maternal smoking and SIDS persisted after controlling for maternal age and live
      birth order. Adjusted odds ratios ranged from 1.6 to 2.5 for mothers who smoked 1
      9 cigarettes per day during pregnancy (compared with nonsmokers) and from 2.3 to
      3.8 for mothers who smoked 10 or more cigarettes per day during pregnancy.
      Although birth weight had a strong independent effect on SIDS, the addition of
      birth weight to the models lowered the odds ratios for maternal smoking only
      slightly, suggesting that the effect of smoking on SIDS is not mediated through
      birth weight. SIDS rates increased with the amount smoked for all US race/ethnic
      groups and for Sweden. Smoking is one of the most important preventable risk
      factors for SIDS, and smoking prevention/intervention programs have the potential
      to substantially lower SIDS rates in the United States and Sweden and presumably
      elsewhere as well.

PMID- 9247010
TI  - Oral contraceptives and ovulatory causes of delayed fertility.
AB  - The return of fertility for women who discontinue oral contraceptives takes
      longer as compared with women who discontinue other methods of contraception. It
      remains unclear, however, whether subsequent fertility differs according to
      duration or age at first use. The authors performed a nested case-control study
      within a cohort of 116,686 female registered nurses residing in 14 US states.
      Baseline information was reported on mailed questionnaires in 1989. Cases
      comprised 1,917 married nurses without previous pregnancy who were unable to
      become pregnant for at least 1 year and were subsequently diagnosed with primary
      ovulatory infertility. Controls comprised 44,521 married parous nurses with no
      history of infertility and no pregnancies lasting less than 6 months. After
      allowing for 2 years of suppressed fertility following discontinuation of oral
      contraceptive use and excluding women with signs of menstrual or hormonal
      disorder, the authors found that the multivariate relative risk for ovulatory
      causes of delayed fertility was 1.2 (95% confidence interval 0.7-1.9) for ever
      users. There was no statistically significant trend of increasing risk with
      increasing duration of use and younger age at first use. The fact that 88 percent
      of cases reported an eventual pregnancy by 1993 suggests that absolute fertility
      was not impaired.

PMID- 9247011
TI  - Evaluating sources of traumatic spinal cord injury surveillance data in Colorado.
AB  - The purpose of this study is to evaluate the sources reporting hospitalized
      spinal cord injury cases to the statewide, population-based surveillance system
      in Colorado for the year 1994. Three reporting sources were evaluated: clinical
      contact persons, medical records departments, and a centralized statewide
      hospital discharge database. Two evaluation strategies were utilized; these
      include both measures of accuracy and estimates of missed cases. For the latter,
      capture-recapture techniques were used to estimate the number of hospitalized
      spinal cord injury cases missed by all three reporting sources. The clinical
      contact persons reported 84 confirmed cases, missed 80 confirmed cases, and
      reported 10 cases that were later determined not to have spinal cord injuries,
      resulting in a sensitivity of 0.51. Medical records departments and the discharge
      database reported 143 and 147 cases, respectively, missed 21 and 17 confirmed
      cases, and reported 118 and 69 cases that were later determined not to be cases
      of hospitalized injuries of the spinal cord, resulting in sensitivities of 0.87
      and 0.90. Capture-recapture results indicate all three sources combined missed an
      estimated 1-5 cases, yielding a total annual incidence rate for hospitalized
      spinal cord injury ranging from 45.1 to 46.3 per million population.

PMID- 9247012
TI  - Risk factors for diarrheal disease incidence in early childhood: a community
      cohort study from Guinea-Bissau.
AB  - To determine risk factors for diarrhea, the authors followed an open cohort of
      1,314 children from Guinea-Bissau by weekly diarrhea recall interviews between
      April 1987 and March 1990. Data on feeding practices and measles infection were
      available for all children and, for 531 children, comprehensive data on
      explanatory variables were recorded. Of 57 variables, seven were independently
      associated with an increased incidence of diarrhea. These were a recent (in the
      past 14 days) diarrheal episode, male sex, being weaned from breast milk, not
      being looked after by the mother, head of the household being < 30 years old,
      eating cold leftovers, and drinking water from an unprotected public water
      supply. In breastfed children, only three variables were associated with
      diarrhea, including prior diarrhea, male sex, and not being looked after by the
      mother. Among weaned children, six variables delineated increased rates of
      diarrhea, including unprotected public water supply, eating of cold leftovers,
      and lack of maternal education. Major determinants of persistent diarrhea
      included weaning, lack of maternal education, and having pigs in the home. It is
      concluded that, in addition to the promotion of breastfeeding, important
      interventions against diarrhea include improvements in water supply, hygiene, and
      food handling. However, because of effect modification by breastfeeding, the
      largest effects of these interventions will probably be among weaned children.

PMID- 9247013
TI  - Re: "Prior to use of estrogen replacement therapy, are users healthier than
      nonusers?".

PMID- 9247014
TI  - Re: "Risk factors for constant, severe trachoma among preschool children in
      Kongwa, Tanzania".

PMID- 9247015
TI  - Restoration of aging reduced immunity is possible with immunomodulators and is
      applicable to cancer treatment and prevention.

PMID- 9247016
TI  - New epidemiologic leads in the etiology of non-Hodgkin lymphoma in the elderly:
      the role of blood transfusion and diet.
AB  - The incidence of non-Hodgkin lymphoma (NHL) in persons over the age of 65 years
      has increased dramatically since the 1950s in western countries. The strongest
      known risk factors for NHL are primary or acquired immunosuppression, but these
      severe deficiencies are relatively rare and cannot explain the rapid increase
      observed in the elderly. Recent work suggests that common exposures which
      influence immunocompetence, albeit at a much weaker level, may also be risk
      factors for NHL. Two such risk factors recently associated with NHL are prior
      history of blood transfusion and certain aspects of diet. In four out of four
      studies, prior history of blood transfusion was associated with approximately a
      doubling in NHL risk, even for a transfusion first received a decade or more
      before diagnosis. Other studies suggest that diets high in animal proteins and
      fats may increase the risk of NHL while fruit and vegetable consumption may
      decrease risk. Allogeneic blood transfusion is known to suppress the immune
      system, and diets high in protein and fat may also lead to altered
      immunocompetence, although other mechanisms such as viral transmission or the
      effects of heterocyclic amines and N-nitroso compounds may also play a role.
      Follow-up of these observations my lead to a better understanding of the NHL
      epidemic and new approaches to the prevention of NHL.

PMID- 9247017
TI  - The treatment of hypertension in older people and its effect on cognitive
      function.
AB  - The benefits of antihypertensive drug therapy for older people have been clearly
      established. Meta-analysis suggests a 12% reduction in all-cause mortality, a 20%
      reduction in coronary heart disease and a 36% reduction in stroke. The absolute
      benefits of treatment are great due to the high incidence of vascular disease
      among older people. Clinicians may nevertheless have been deterred from
      initiating treatment because of concerns regarding adverse effects on cognition,
      mood, functional ability and quality of life. Recent evidence from randomised
      controlled trials suggests that these concerns are groundless. In the light of
      this evidence it is therefore disturbing that up to 50% of all older people with
      hypertension may remain untreated; and in over 50% of those who are treated,
      blood pressure may be inadequately controlled.

PMID- 9247018
TI  - Longitudinal stress leg fracture in the elderly.
AB  - Among longitudinal stress fractures, tibial fracture was described in 1960 by
      Devas in the UK, and is still an uncommon occurrence. To our knowledge,
      longitudinal stress fracture of the fibula has not been described previously, but
      only the transversal type. Patients complain of pain in the tibial or fibular
      side of the ankle, whereas the X-rays are normal. However, unusual physical
      activity is noted in all patients, and the diagnosis is that of a suspected
      stress fracture. Bone scan shows quite widespread increased radionuclear intake.
      CT scan shows the stress fracture. Restriction of activity for one month results
      in complete disappearance of pain in all cases.

PMID- 9247019
TI  - Pilot study for preoperative administration of l-OHP to patients with advanced
      scirrhous type gastric cancer.
AB  - A new DACH platinum complex, l-OHP, was developed by Kidani as an anticancer
      agent. A clinical trial took place in Europe which demonstrated its therapeutic
      efficacy for colorectal cancer. An effective treatment, especially chemotherapy
      for patients with a advanced scirrhous type gastric cancer, has not yet been
      established. An in vitro study showed that l-HOP inhibited cell growth in human
      gastric cancer cell lines. Our pilot study determined the efficacy of
      preoperative administration of l-OHP, 67 mg/m2 to 100 mg/m2, every 2-3 weeks, for
      two to three cycles, in five patients with this disease (Stage III and IV)
      roentogenoscopically and histologically. The platinum concentration in the
      tissues was also measured. By X-ray examination of the stomach at the time of pre
      and post-administration of l-OHP, extension of the lesional gastric wall was
      observed. Histologically three Grade 2 responses and two Grade 1a responses were
      obtained according to the criteria presented by Japanese Research Society for
      Gastric Cancer. The mean platinum concentrations in the lesional tissues were
      0.98 ppm and 0.5 ppm in the patients administered l-OHP for three and two cycles
      respectively. There was no toxicity that prevented surgery. These preliminary
      results showed the possibility that 1-OHP would be effective for patients with
      advanced scirrhous type gastric cancer as a neoadjuvant therapy.

PMID- 9247020
TI  - Homeostasis of chemokines, interferon production and lymphocyte subsets:
      implications for AIDS pathogenesis.
AB  - Certain individuals with elevated levels of macrophage inflammatory protein
      (MIP)1 alpha, MIP1 beta and RANTES expression appear to be resistant to human
      immunodeficiency virus (HIV) infection. In this work, we demonstrate that
      chemokines production by peripheral blood mononuclear cells (PBMCs) are
      homeostatic parameters varying from one individual to another, and we define
      optimized experimental conditions to reproducibly assess these parameters. We
      also studied alpha- and gamma-interferons (IFN alpha and IFN gamma, respectively)
      which have been implicated in the pathogenesis of acquired immunodeficiency
      syndrome (AIDS). The kinetics of production of all these cytokines by fresh PBMCs
      were determined upon stimulation with phytohemagglutinin (PHA), staphylococcus
      enterotoxin b (SEB) and purified protein derivative (PPD). RANTES and MIP1 alpha
      are produced early in response to activation, followed by MIP1 beta, (alpha
      interferon, gamma-interferon, alpha IFN, gamma-IFN alpha and IFN alpha and gamma.
      These results suggest that using our methodology, chemokines levels can be
      reliably determined, permitting the performance of accurate genetic studies using
      PBMCs from various cohorts (siblings or AIDS related cohorts).

PMID- 9247021
TI  - Human deoxycytidine kinase as a conditional mutator in Escherichia coli.
AB  - The chemical diversification of DNA precursors was undertaken in Escherichia coil
      by expressing the human gene for deoxycytidine kinase, and supplying such
      recombinant strains with nucleoside analogues bearing an altered base or sugar.
      Arabinocytidine and dideoxycytidine thus became highly toxic to E. coli in the
      sub-millimolar range. Deoxynucleosides bearing isoadenine (2-aminopurine) and
      isoguanine (2-hydroxy-6-aminopurine) showed a high mutagenic potency towards the
      recombinant strains, to an extent comparable to that of the most efficient
      mutator alleles (dnaQ). These findings open the way to the propagation of
      chemically remodelled nucleic acids and to the controlled hypermutagenesis of
      plasmids in vivo.

PMID- 9247022
TI  - Biological role of carbamoyl pyridoxal 5'-phosphate.
AB  - A new compound, carbamoyl-pyridoxal 5'-phosphate (C-PLP), was synthetized by
      condensation of pyridoxal 5'-phosphate (PLP) with KCNO. It may be obtained under
      certain physiological conditions of pH, temperature and concentration of
      reagents. Formation and degradation of C-PLP are readily reversible chemical
      reactions, not involving enzymes, at least in rat tissues. However, different
      considerations suggest that synthesis and breakdown of C-PLP play a biological
      role in the cell, providing 'protective synthesis' and a 'variable reservoir' of
      PLP and KCNO, which can be trapped by other proteins, apoenzymes and metabolites,
      to regulate many cell metabolic functions.

PMID- 9247023
TI  - Purification and characterization of a type 2A protein phosphatase from Yarrowia
      lipolytica grown on a phosphate-deficient medium.
AB  - Intracellular protein phosphatase activity has been identified in the yeast
      Yarrowia lipolytica. This activity was maximal early in its exponential growth
      phase, and it was enhanced by Pi-deficiency of the culture medium. On a Pi
      deficient medium, the major protein phosphatase was purified. This enzyme was
      dissociated with 80% ethanol treatment, its activity was slightly increased (30%)
      with heparine and largely enhanced (1.5 to 3-fold) with polycations. This enzyme
      could be classified as a type 2A protein phosphatase. It is composed of a
      catalytic subunit and other subunits. Its optimum pH value is 7.2, the apparent
      Km for casein is 37 microM and the apparent velocity 3.6 pmol hydrolyzed32 Pi min
      1 pmol-1 enzyme.

PMID- 9247024
TI  - [Comparison of daily alkaline phosphatase activity of a cyanobacterium
      (Microcystis aeruginosa) and a diatom (Synedra capitata)].
AB  - Alkaline phosphatase activity (ALP) (EC: 3.1.3.1) presents a nycthemeral
      variation in both Microcystis aeruginosa (cyanobacterium) and Synedra capitata
      (diatom) species. Nevertheless, a comparative study reveals differences between
      the enzymatic behaviour of these two species. ALP is 33 times higher in
      cyanobacteria than in diatoms under similar experimental conditions. Microcystis
      aeruginosa presents therefore a larger capacity for mineralizing organic
      phosphorus per unit of biomass. Under LD (16:8) conditions, diatoms show a higher
      enzymatic activity during the day time (around 0.12 mumol pNPP/mn/mg); on the
      contrary, cyanobacterial enzymatic activity is rather low during the day time and
      rises at the beginning of night time (around 3.5 mumol pNPP/mn/mg). Finally, the
      mean of ALP of Synedra capitata is maximal (around 0.12 mumol pNPP/mn/mg) under
      total darkness (DD) while the mean of enzymatic activity is maximal (around 3.58
      mumol pNPP/mn/mg) under permanent light (LL) for the cyanobacteria. These
      observed differences in the alkaline phosphatase activity between Microcystis
      aeruginosa and Synedra capitata might, to some extent, explain the observed
      alternances within the planktonic settlements between algae and cyanobacteria in
      hypereutrophic lakes such as the Grangent reservoir (Loire).

PMID- 9247025
TI  - Primary structure of a myohemerythrin-like cadmium-binding protein, isolated from
      a terrestrial annelid oligochaete.
AB  - Two isoforms of a cadmium-binding protein (Cd-BP 14a and Cd-BP 14b) were isolated
      from the terrestrial oligochaete annelid, Allolobophora caliginosa. The complete
      amino acid sequence of the major isoform Cd-BP 14a (molecular mass: 13441 Da; 119
      residues) and the amino-terminal sequence (57 residues) of Cd-BP 14b were
      determined. The sequence of Cd-BP 14a is highly similar to that of
      myohemerythrins present in marine invertebrates. Furthermore, as myohemerythrins,
      Cd-BP 14a and Cd-BP 14b bind two atoms of iron and their ultraviolet/visible
      spectra are typical of non-heme iron-binding proteins. Three substitutions were
      found in the amino-terminal half of the proteins at positions 19, 21 and 41. The
      substitutions at positions 19 and 21 are conservative, whereas that at position
      41 consists of the replacement of an aspartate residue in isoform a by a lysine
      residue in isoform b. To our knowledge, it is the first report of a protein
      belonging to the hemerythrin family in a terrestrial invertebrate.

PMID- 9247026
TI  - Phylogenetic relationships among Indriidae (Primates, Strepsirhini) inferred from
      highly repeated DNA band patterns.
AB  - Comparative studies of highly repeated DNA from different species of Indriidae
      (Primates, Strepsirhini) allowed confirmation of the specific status of Avahi
      occidentalis, A. laniger and Propithecus tattersalli. The comparison of their
      band patterns revealed the existence of specific and common bands from which a
      cladogram of the family is inferred. This cladogram shows that Avahi clade is the
      sister-group of Indri and Propithecus clade, and that P. verreauxi is related to
      P. diadema. These results were discussed in view of those obtained from
      cytogenetic, morphological and molecular data (mitochondrial DNA). This study
      shows the capacity of the repeated sequence pattern comparison to be used as a
      tool for confirming taxa status, (taxinomic classification is a primary
      determinant of management priorities for endangered species, neglect of distinct
      taxa may lead to their extinction), and for inferring phylogenetic relationships
      among related species.

PMID- 9247027
TI  - [A simple method for the study of cytosolic content of oligonucleotides in
      cells].
AB  - Antisense oligonucleotides are currently used for the specific control of the
      expression of a selected gene. Their putative targets are located in the
      cytoplasm (messenger RNA) or the nucleus (pre-messenger RNA or DNA). This
      approach is conditioned by the presence of the antisense molecule inside the cell
      at sufficient concentrations and in the appropriate compartments. We propose in
      this paper a simple method for the study of the cytosolic content of internalized
      oligonucleotides. This method is based on the selective permeabilization of the
      plasmic membrane by the detergent digitonin. By complexing to membrane
      cholesterol, the detergent creates pores through which soluble and diffusible
      species can escape outside the cells. The selectivity of membrane
      permeabilization was controlled by using compartment markers: lactate
      dehydrogenase (LDH) for cytosol, dextrane-rhodamine (DEX) and hexosaminidase
      (HAM) for endocytic vesicles and lysosomes, respectively. Optimal digitonin
      concentrations and incubation times have been defined to reach the following
      pattern of membrane permeabilization: LDH > 80%; DEX and HAM < 15%. The method
      was applied to monitor the quantity of extractible oligonucleotides from cells
      after endocytosis. The results showed that phosphodiester and phosphorothioate
      oligomers are readily available in the cytosol (60-50% of the internalized
      species), whereas those bearing a hydrophobic moiety (fluorescein, cholesterol)
      are less diffusible probably owing to membrane binding. Internalization and
      cytosol partition were found to depend on the chemical nature of the
      oligonucleotide, and also on the sequence and the cell type. This method could be
      useful for the selection of antisense molecules that exhibit the best
      internalization and distribution in cells, and for a more appropriate choice of
      control sequences in antisense studies.

PMID- 9247028
TI  - [Morphological study of Organum cavum pre-lamina terminalis (OCPLT), implicated
      in thirst in rats].
AB  - It has been shown that micro-injections of angiotensin II in the Organum cavum
      pre-lamina terminalis (OCPLT) of the rat brain trigger water intake. Our
      anatomical study shows that the anterior, vertical extension of this Organum
      corresponds to the anterior inter-hemispheric fissure, and its posterior,
      horizontal extension to the Cavum septi pellucidi (CSP). Contrary to classical
      descriptions, the CSP persists in the adult rat, though reduced to one third of
      its initial antero-posterior extension. It appears rostrally as an opening into
      the anterior inter-hemispheric fissure. The absence of ependymal cells and of
      communication with the lateral ventricles points to the fact that this
      diverticulum is not a median cerebral ventricle. Its pial sheathing and the
      presence of leptomenix in the cavity confirm its inter-hemispheric origin. The
      pinocytotic vesicles of the meningeal capillaries suggest an active transfer of
      substances. Circumstantial evidence suggests circulating angiotensin could be one
      of them.

PMID- 9247029
TI  - Expression of HIV-1 nef decreases basal phosphatidyl-inositol 3-kinase activity.
AB  - CEM lymphoid cells expressing high levels of HIV-1 nef protein displayed a
      significant decrease in basal phosphatidyl-inositol 3-kinase (P13-kinase)
      activity associated with immunoprecipitates with anti-p85 regulatory subunit. In
      contrast, chronically infected U937 monocytic cells displayed a significant
      increase in basal P13-kinase activity in cells infected with HIV-1 nef compared
      to those infected with isogenic HIV-1 nef+. These findings suggest that HIV-1-nef
      expression is accompanied by a decrease in basal intracellular phosphatidyl
      inositol 3-kinase activity and suggest that P13-kinase could be important for HIV
      1 replication. Moreover, wortmannin, a potent in-vitro phosphatidyl-inositol 3
      kinase inhibitor, can inhibit HIV-1 replication in U937 chronically infected
      cells. Together these results suggest a correlation between P13-kinase activity
      and HIV-1 replication.

PMID- 9247030
TI  - [Viruses and macrophages].

PMID- 9247031
TI  - The biology of macrophages.
AB  - The main properties of the mononuclear phagocytic system (MPS) are summarized,
      focusing on their relevance within the framework of the steady-state and the
      inducible functions of the mammalian immune system, more specifically the immune
      system of the laboratory mouse, a reference vertebrate which remains the best
      studied. A peculiar attention is given to the rationale underlying the generation
      of so-called specific tools and reagents whose use is promoted to characterize
      this lineage, whatever the level under study, i.e. tissular, cellular, or
      subcellular levels. As one lineage among other lineages of the hemopoietic
      system, the MPS is characterizable by constitutive and inducible phenotypic and
      functional markers whose combination is unique for a given tissular micro
      environment. Considering our present understanding of the innate and adaptive
      immune system functions, some of the properties of the MPS are discussed in
      relation with properties of another recently recognized hemopoietic lineage,
      namely the dendritic leukocyte system.

PMID- 9247032
TI  - [Nitric oxide and macrophages].
AB  - Nitric oxide (NO) is a gaseous radical enzymatically produced from L-arginine by
      virtually every cell. This versatile molecule is involved in a variety of
      biological functions including defense against pathogens. Micro-organisms whose
      development is inhibited by NO include fungi, bacteria, protozoa, helminths and
      viruses. In murine macrophages, a high output NO synthase (NOS II) is regulated
      transcriptionally by cytokines and microbial products. In the past few years,
      investigators have identified many other cell types expressing NOS II. However,
      in human monocytes/macrophages, the existence of the L-arginine-NO pathway has
      long been questioned. Recent findings and new developments in this respect are
      commented in this short review.

PMID- 9247033
TI  - Cytokines, viruses and macrophages: an interactive network. An immune
      dysregulation involving the members of the tumor necrosis factor (TNF) receptor
      superfamily could be critical in AIDS pathogenesis.
AB  - Both macrophages and cytokines are components of the immune defense against viral
      infections. Among cytokines, interferons have been the most studied and
      interferon-gamma which is secreted by T cells and NK cells activates macrophages
      which synthesize both interferon-alpha and -beta which have powerful antiviral
      activity. Aside from interferons other cytokines such as tumor necrosis factor
      alpha and transforming growth factor-beta display an antiviral activity.
      Nevertheless often cytokines could mediate distinct actions in regard to viral
      infection and this has been demonstrated extensively in AIDS pathogenesis. We
      reviewed among others the interactions between human immunodeficiency virus type
      1, macrophages and cytokines and would like to forward a new model for AIDS
      pathogenesis based on the involvement of the TNF receptor superfamily.

PMID- 9247034
TI  - [Antigen presentation and macrophages].
AB  - T-cells recognize antigenic peptides associated with HLA molecules belonging to
      Class I (HLA-A, -B, or -C) or Class II (HLA-DP, -DQ, -DR). Roughly, Class I HLA
      molecules represent antigens to cytotoxic CD8+ T-cells and Class II HLA molecules
      to helper CD4+ T-cells. Class II HLA molecules primarily present "exogenic"
      peptides that penetrate within cells by endocytosis, whereas Class I HLA
      molecules present "endogenic" peptides produced within cells. In both cases, the
      mechanisms of antigen presentation are closely liked to the biosynthesis of HLA
      molecules and to the expression of other molecules including proteasome (LMP) and
      the peptide transporters (TAP) needed to transport peptides through the
      endoplasmic reticulum in the case of Class I molecules, and invariant chain (Ii)
      and HLA-DM antigens in the case of Class II molecules. In addition, "exogenous"
      presentation by Class I molecules has recently been described, and may be
      relatively specific of phagocytic cells such as macrophages.

PMID- 9247035
TI  - [Lymphohistiocyte activation syndromes associated with Epstein-Barr virus].
AB  - Lymphohistiocyte activation syndromes associated with the Epstein-Barr virus and
      characterized by activation and proliferation of T-cells and macrophages
      reflecting an inappropriate response of the host to the viral infection. The
      clinical manifestations are often alarming symptoms suggestive of severe sepsis.
      Most patients have a known underlying disease (hemopathy, lupus, Still's disease,
      HIV infection, bone marrow or organ transplantation). In the few cases that occur
      in the apparent absence of any risk factors, investigations should be done to
      look for a predisposing inherited disease, such as familial lymphohistiocytosis
      of Purtilo syndrome in boys. The treatment rests on immunosuppressive agents
      followed by bone marrow transplantation, which can provide a definitive cure in
      genetic forms.

PMID- 9247036
TI  - [HIV and macrophage].
AB  - The macrophage is the chief target of the HIV, as well as its main vector.
      Macrophages are infected very early by monocytotropic HIV strains. They are not
      destroyed, and probably contribute both to host defense mechanisms and to
      perpetuation and dissemination of the infection. HIV-infected macrophages have
      been demonstrated not only in lymph nodes but also in peripheral organs such as
      the lung and brain, where they produce cytotoxic mediators that contribute to the
      development of pulmonary and neurologic lesions. Functional impairment of HIV
      infected macrophages may play a role in the immune deficiency characteristic of
      AIDS. Infected macrophages are a reservoir and a sanctuary for the HIV, by virtue
      of which the virus can escape detection by the immunologic surveillance system.
      This set of properties makes the HIV-infected macrophage an ideal agent of the
      propagation and perpetuation of HIV infection. Work aimed at unraveling the
      cellular and molecular mechanisms that underlie HIV-macrophage interactions can
      be expected to result in new therapeutic strategies.

PMID- 9247037
TI  - Interaction of human cytomegalovirus with monocytes/macrophages: a love-hate
      relationship.
AB  - This review addresses the complex interactions of human cytomegalovirus (CMV)
      with the phagocytic mononuclear cell system. Certain aspects may be supplemented
      with observations made in animal systems. An attempt will be made to summarize
      information acquired through in vivo studies about the distribution of CMV in the
      mononuclear phagocyte cells, the state of the virus in such cells and the
      reactivation of virus in this setting. Much information has been gained through
      in vitro experimentation attempting to elucidate the infectability of and
      replication in monocytes/macrophages, and the role played by the cellular
      differentiation in these events. The influence of CMV infection on the generation
      of macrophages and granulocytes from bone marrow progenitors will also be
      examined. The modifications of host cell function induced by CMV infection,
      notably the production of cytokines and antigen presentation will be examined.
      The possible significance of CMV infection of monocytes/macrophages relative to
      viral dissemination, immunosuppression, and hematological modifications
      associated with CMV infection will be discussed.

PMID- 9247038
TI  - [Herpes simplex virus and macrophages].
AB  - Macrophages, widely distributed in the body, play a central role in mediating
      host defense against herpes simplex virus (HSV) infections. Both intrinsic
      antiviral activities of macrophages (phagocytic and degradative function leading
      to presentation of viral antigens, inhibition of viral replication) and extrinsic
      antiviral resistance (inhibition of the spread of HSV, inhibition of HSV
      replication in permissive cells and selecting lysing of HSV-infected cells) are
      modulated by cytokines such as interferons (IFN) and tumor necrosis factor (TNF).
      Macrophages in the presence of an interactive network of cytokines are involved
      in the orchestration of non specific host defense and specific immune responses
      against HSV infections. Further investigations of physiopathology and complex
      interactions of macrophages-HSV should lead to the development of immunotherapy
      for HSV infections in immunocompromised individuals.

PMID- 9247039
TI  - [Role of macrophages in papillomavirus infections].
AB  - Papillomaviruses have naturally a strict tropism to epithelial cells in which
      they replicate during the cell differentiation. There is no histological evidence
      of any inflammatory reaction. No leucocyte recruitment is observed and thus, the
      role of macrophages during the early infectious process in the epithelium remains
      unknown. This silent, subacute or chronic infectious disease is characterized
      fundamentally by a dual pathogenic process, including an infectious process
      leading to the production of infective virus particles during the differentiation
      of infected epithelial cells, on the one hand, and an oncogenic process due to
      interactions of viral oncogenes with host cell regulatory proteins after
      integration of the virus to the cellular genome. The role of activated
      macrophages on the oncogenic process is clearly established. They contribute to
      regulate negatively the transcription of the non structural E6 E7 viral oncogenes
      and have cytotoxic effects to transformed cells by a direct intercellular contact
      without evidence of an effect due to a soluble factor such as tumor-necrotizing
      factor (TNF). Macrophages have, hence, a prominent role as cellular effectors of
      protective immunity against lesions due to papillomaviruses and particularly
      against the oncogenic process complicating these infections.

PMID- 9247040
TI  - [Hepatic macrophages and virus].
AB  - Kupffer cells are located at strategic positions in the liver sinusoids. They are
      involved in the clearance of about 90% of foreign particles namely viruses and
      play an important role in the pathogenesis since their interaction with viruses
      represents a major determinant of viremia. On the one hand, they may protect the
      host from the infection by taking up and degrading the viral particles as well as
      by presenting antigen to lymphocytes, on the other hand, they may enhance the
      infection by producing and disseminating viruses when they are permissive. When
      they are activated or when they produce interferon alpha, Kupffer cells exert an
      antiviral effect on adjacent cells. Moreover they participate to the inflammatory
      response by synthesizing numerous mediators. Their destruction as well as the
      alteration of their functional properties may have serious physiopathological
      consequences.

PMID- 9247041
TI  - Macrophages and respiratory viruses.
AB  - This review highlights some of the interactions between alveolar macrophages and
      human/swine influenza A viruses, porcine reproductive and respiratory syndrome
      virus (PRRSV), bovine parainfluenza type-3 (PI-3) virus, bovine respiratory
      syncytial virus (BRSV) and bovine viral diarrhoea virus (BVDV). In influenza A
      infection, macrophage-cytokines are believed to mediate the typical
      constitutional effects and inflammation in the respiratory tract. The same
      cytokines possibly play a role in influenza-bacterial respiratory disease. PRRSV
      has a very restricted tropism for alveolar macrophages. The virus causes some
      secondary infections to be more severe, but this could not be related to impaired
      macrophage functions. Bovine RSV and PI-3 virus, on the other hand, interfere
      with selected macrophage functions. In addition, PI-3 virus adversely affects
      lymphocyte proliferation because it interferes with the accessory role of
      macrophages. One of the characteristic effects of BVDV on monocytes-macrophages
      is stimulation of prostaglandin E2 production.

PMID- 9247042
TI  - [Preventing and treating venous thrombosis in 1997].

PMID- 9247043
TI  - [Infectious complications of implantable infusion ports in patients with HIV
      infection].
AB  - Thirty-four implantable ports were consecutively implanted in 27 AIDS patients
      (mean CD4 lymphocyte count: 39/mm3) from January 1993 to December 1995. We
      observed 33 complications in these patients. Perioperative complications
      included: one pneumothorax (3%), one haematothorax (3%) and one septic shock
      (3%). Later complications included one venous thrombosis (3%) and 26 infectious
      complications (79%). Fever of unknown origin was observed in three patients (9%).
      A total of 19 bacteremias occurred in 12 patients. The global rate of infection
      for 100 catheter-days was 0.51 for a total of 5,096 catheter-days. The following
      microorganisms were isolated: Staphylococcus (n = 21; 72%), Pseudomonas (n = 3;
      11%) and others (n = 5; 17%). Thirty-eight percent of the ports (n = 13) were
      removed, after a mean of 89 days. During the study, 21 patients died. Two
      patients died from a catheter infection with septic shock (8%). It seems to be
      important to clearly define the indications of implantable infusions ports in
      AIDS patients with respect to their life expectancy.

PMID- 9247045
TI  - [Sanitary impact of air conditioning: what is the relation to sick building
      syndrome?].
AB  - Modern architecture is creating air-conditioned offices in our society. Various
      diseases have been associated with conditioned air exposure, and building-related
      diseases are distinct from sick building syndrome (SBS). Building-related
      diseases have a well-characterized aetiology, essentially infectious, compared to
      SBS, where the aetiology is not clear. This paper reviews these syndromes, their
      aetiologies and their discussion in order to treat and prevent their expression.
      Progress has been made in the conception of air-conditioning systems. Prevention
      of these syndromes is based on conception and cleaning of these systems, which
      allows the use of air-conditioning without any major sanitary problem.

PMID- 9247044
TI  - [New antithrombotic agents in coronary disease].
AB  - Aspirin is effective in, treating patients with unstable angina or myocardial
      infarction. However, questions remain about the optimal dose of aspirin and
      aspirin-resistance in subgroups of patients. Heparin also has beneficial effects
      mostly during the acute phase of unstable angina, but thrombolytics are effective
      only in acute myocardial infarction and not in unstable angina. Recently, low
      molecular weight heparins have proved to be as effective (FRIC trial) or more
      effective (ESSENCE trial) than unfractionated heparin in unstable angina. Ongoing
      studies (TIMI 11B) are evaluating the efficacy of a prolonged administration of
      low molecular weight heparin to alter the chronic process of unstable angina. The
      new antiplatelet drugs directed against GP IIb/IIIa receptors are now available
      to improve the acute results of high risk percutaneous transluminal angioplasty
      (PTCA). This new drug (c7E3) binds rapidly to GP IIb/IIIa and prevents fibrinogen
      binding to the receptor. This very potent and irreversible effect prevents
      platelet aggregation and decreases the incidence of acute occlusions following
      PTCA. especially in patients with unstable angina. The counterpart is an
      increased risk of hemorrhage, knowing that patients receive simultaneously
      aspirin and heparin. The first results of the EPILOG study also demonstrate a
      better outcome in elective angioplasty without significant increase of serious
      bleeding, thanks to a low dose heparin regimen. In contrast to thrombolytics, the
      GP IIb/IIIa antagonist does not increase the risk of intracranial bleeding. The
      results of the CAPTURE trial also confirm the clinical benefit obtained with this
      drug in refractory unstable angina. The reduction of death and myocardial
      infarction is very consistent throughout the studies performed with c7E3. The
      Kaplan-Meier curves of freedom of death and myocardial infarction diverge
      immediately after start of study medication. The acute benefits are preserved at
      3 years in the EPIC trial. Similar trends were present during the acute phase
      with other compounds (tirofiban, integrelin), meaning that a class effect may
      exist but the long term results are disappointing. The results with new direct
      antithrombins such as hirudin, or hirulog in acute myocardial infarction or in
      PTCA for unstable angina are negative. The development of new potent oral
      antiplatelet drugs might change the treatment of acute coronary syndromes in the
      future. The current progress made with antithrombotic drugs should improve the
      prognosis of acute coronary syndromes.

PMID- 9247046
TI  - [Triclonal gammopathy and malignant immunoproliferative syndrome].
AB  - Three distinct monoclonal gammopathies were identified in the serum of a 79 year
      old man. In 1972 he presented with Waldenstrom's macroglobulinemia IgM Kappa.
      Twenty years later multiple myeloma was diagnoses. Serum protein electrophoresis
      performed at this time showed three monoclonal bands. Immunofixation identified
      these bands as monoclonal IgM kappa, IgG kappa and IgA kappa. Twenty-six cases of
      triclonal gammopathies were previously reported. Sixteen cases were associated
      with malignant immuno-proliferative diseases (non-hodgkin lymphoma, Waldenstrom's
      macroglobulinemia, multiple myeloma); five cases with non-hematologic diseases;
      three cases were of undetermined significance. The origin of three distinct
      monoclonal proteins may derive from three unrelated clones or alternatively from
      a single clone in which an isotype switch has occurred.

PMID- 9247047
TI  - [Gouty encephalopathy: myth or reality?].
AB  - Case report is a 75-year old woman who presented an unexplained febrile
      encephalopathy with diffuse myoclonic jerks and a gout's polyarthritis. None of
      these etiologies was found: infectious, toxic, vascular, metabolic, hormonal,
      immunologic. The spectacular effect on neurologic symptoms of a treatment by
      colchicine alone lead us to consider that gout encephalopathy probably exists.

PMID- 9247048
TI  - [Cutaneous metastatic Crohn disease. Apropos of a case].
AB  - The authors report the case of a 54-year old man suffering from facial
      papulonodular eruption. He has Crohn's disease which was diagnosed 36 years ago.
      There were no clinical symptoms of the disease when the cutaneous manifestations
      occurred. The biopsy of a cutaneous lesion showed cutaneous granuloma at skin's
      level. Having no other etiology, we shall diagnose it as a cutaneous metastatic
      Crohn's disease. Derived sulfasalazine (Pentasa) healed all lesions in 1 month.
      This observation reminded us to that it is essential to biopsy all atypical
      cutaneous lesions occurring in a Crohn's disease case.

PMID- 9247049
TI  - [Malignant endovascular large-cell lymphoma: disclosing central nervous system
      involvement confirmed by cerebral biopsy].
AB  - Intravascular malignant lymphomatosis (IML) is characterised by proliferation of
      tumoral cells within small vessels. Angiotropic large cell lymphoma commonly
      affects the central nervous system and the skin, although any organ may be
      involved. Few cases are diagnosed ante mortem. We report a new case of IML in a
      62-year-old woman who presented with the main clinical features of central
      nervous system involvement: cerebrovascular events, epileptic seizures, subacute
      dementia and spinal cord syndrome. Cranial magnetic resonance imaging
      demonstrated increased periventricular signal on T2-weighted images. Diagnosis
      was established by brain biopsy. Despite corticosteroid and radiation therapy no
      improvement occurred and the patient died 14 months after the onset of the first
      symptoms.

PMID- 9247050
TI  - [Lines of conduct for training of physicians in echography and vascular Doppler
      and realization of vascular ultrasonic tests].
AB  - Vascular tests with duplex scanning have an important lace in the diagnostic and
      therapeutic strategy in vascular medicine; they are integrated by the physician
      within the strategy of pathology support. The realization and interpretation of
      vascular duplex scanning are subject to recommendations. The training of
      physicians takes into account the clinical context due to the fact that all
      aspects of these examinations are inseparable. Besides the theoretical education,
      it is important to be thorough in practical training. The realization of a
      minimal number of 250 examinations is advised, distributed among different
      sectors of anatomy and pathology. The acquiring and preservation of technical
      skills and the ability to provise solutions, requires the realization of
      additional 250 examinations. This total amount of 500 examinations is integrated
      into a global 2 year educational program. The preservation of skills requires 500
      annual examinations. The training center is placed under the responsibility of a
      clinical physician, recognized in vascular medicine. This center must perform
      more than 2,000 examinations a year. Various centers can associate their
      abilities in order to ensure a complete training program.

PMID- 9247051
TI  - [Tripe palms].

PMID- 9247052
TI  - [Is hepatitis B vaccination a new cause of necrotizing vasculitis?].

PMID- 9247053
TI  - [Transient Sjogren syndrome with pancreatic involvement].

PMID- 9247054
TI  - [Staphylococcus aureus purulent pericarditis in a patient with AIDS].

PMID- 9247055
TI  - [Yellow nail syndrome associated with rheumatoid arthritis. Regression under
      chrysotherapy].

PMID- 9247056
TI  - [Chondritis of the ears in a patient with primary antiphospholipid syndrome].

PMID- 9247057
TI  - Distribution of sodium channels in chronically demyelinated spinal cord axons:
      immunoultrastructural localization and electrophysiological observations. Brain
      Research 544 (1991) 59-70.

PMID- 9247058
TI  - The voltage-dependent sodium channel in mammalian CNS and PNS antibody
      characterization and immunocytochemical localization. Brain Research 532 (1990)
      222-231.

PMID- 9247059
TI  - Sodium channels in the cytoplasm of Schwann cells. Proc. Natl. Acad. Sci. 87
      (1990) 9290-9294.

PMID- 9247060
TI  - Evidence for pore-like opening of the blood-brain barrier following forebrain
      ischemia in rats.
AB  - The nature of the delayed blood-brain barrier (BBB) opening that occurs in rats
      subjected to forebrain ischemia by the technique of two-vessel (carotid)
      occlusion plus hypovolemic hypotension (2VO ischemia) was probed by examining the
      simultaneous, trans-barrier movement of two hydrophilic, normally poorly
      permeative solutes of markedly different molecular size: sucrose (MW = 342) and
      inulin (MW approximately 5000). Pentobarbital-anesthetized, male, Sprague-Dawley
      rats (342-374 g) were subjected to 10 min of 2VO ischemia (tympanic temperature,
      37.5-38.0 degrees C); 6 h later they were reanesthetized and, along with non
      ischemic controls, injected i.v. with [14C]sucrose and [3H]inulin. Transfer
      constants (Kis) for blood-to-brain movement of the tracers and Vis (apparent
      initial volumes of tracer distribution) were determined for six brain regions by
      the multiple-time, graphical method (tracer circulation times from 3 to 30 min).
      Vis differed little or insignificantly between the two tracers, or between
      control and post-ischemic rats; the values did not suggest appreciable
      endothelial binding of either tracer that might lead to its uptake by adsorptive
      phase endocytosis. In the controls, regional Kis +/- S.E.M. (nl g(-1) s(-1)) for
      inulin ranged from 0.18 +/- 0.04 to 0.31 +/- 0.09 and were significantly lower (P
      < 0.01) than Kis for sucrose (1.53 +/- 0.16-1.91 +/- 0.29). The Ki ratio
      (sucrose/inulin) across brain regions (mean, 6.6; S.E.M., 0.6) was much lower
      than would be expected according to the concept that movement of most organic non
      electrolytes across the intact BBB occurs by dissolution in and diffusion through
      endothelial cell plasma membranes, at a rate proportional to the lipid solubility
      and diffusivity of the solute. This finding is interpreted as indicating that a
      portion of the transfer of sucrose and inulin occurred by a mechanism other than
      dissolution-diffusion (e.g., via pores or vesicles). In the post-ischemic rats,
      Kis for both tracers were elevated significantly (P < 0.01) in parietal cortex,
      striatum, hippocampus, and midbrain. The post-ischemic increases (delta Kis) in
      these regions were greater for sucrose (1.90-3.31 nl g(-1) s(-1)) than for inulin
      (0.80-1.33). Across brain regions the ratio between sucrose delta Ki and inulin
      delta Ki averaged 2.9 (S.E.M., 0.2), a value significantly greater than the ratio
      of 1 that would be expected were the BBB opening due to an enhancement of
      micropinocytosis and vesicular transport. The correspondence of the mean delta Ki
      ratio with the ratio of the free diffusion coefficients of the tracers (D(f,
      suc)/D(f, inu) = 2.9; water, 38 degrees C) suggests that the delayed opening of
      the BBB following 2VO ischemia involves the formation of trans- or paracellular,
      aqueous pores or channels.

PMID- 9247061
TI  - Thrombin receptor on rat primary hippocampal neurons: coupled calcium and cAMP
      responses.
AB  - We have tested the hypothesis that hippocampal neurons respond to thrombin via a
      neuronal thrombin receptor. A human neuroblastoma cell line, SK-N-SH, known to be
      thrombin responsive morphologically, responded both to thrombin and thrombin
      receptor agonist peptide (TRAP 42-55) with elevation of intracellular calcium. In
      Western blots of membranes from SK-N-SH cells and cultured rat hippocampal
      neurons using an antibody against the N-terminal peptide of the human thrombin
      receptor, putative receptor proteins of 66 and 47 kDa were detected in both
      cells. Neurons were treated with thrombin and TRAP 42-55 (TRAP-14) to determine
      their effects on intracellular levels of calcium and cAMP. Only 10% of the
      neurons showed a rapid response to thrombin, but most responded rapidly to
      agonist peptide with a prolonged elevation of intracellular free calcium.
      Neuronal cAMP levels were decreased by 40% after 24 h thrombin treatment. This
      decrease in cAMP level could be blocked by both the Gi-protein inhibitor,
      pertussis toxin, and the thrombin inhibitor, hirudin, suggesting a possible
      involvement of Gi-protein-coupled receptor activation. Furthermore, rapid calcium
      and cAMP responses were apparently induced by pre-treatment of neurons with
      thrombin for 24 h and subsequent washout. In summary, these data indicate that
      rat primary hippocampal neurons have thrombin receptors whose responses to
      thrombin apparently are up-regulated by 24 h thrombin pre-treatment. These
      results may have implications for synaptic remodeling, learning and memory.

PMID- 9247062
TI  - Effect of p-chlorophenylalanine (PCPA) on sleep and monoamines content in the
      brain of a lizard species.
AB  - Administration of PCPA, a specific inhibitor of serotonin synthesis, induced a
      significant decrease of total sleep time in the lizard Ctenosaura pectinata. This
      effect was exerted on both quiet sleep and active sleep, but it was more intense
      on active sleep. Reduction in the amount of active sleep was due to a decrease in
      the number of the episodes not in their mean duration, since this parameter
      increased significantly from 5.97 s, under control conditions, to 11.77 s, 10.66
      s and 8.85 s at 24, 48 and 72 h after PCPA injection, respectively. Neurochemical
      analysis showed a significant decrease in the amount of serotonin in the analyzed
      brain stem structures 12 h after PCPA administration. The possible participation
      of serotonergic mechanisms in the regulation of reptilian sleep is discussed.

PMID- 9247063
TI  - Histological markers of neuronal, axonal and astrocytic changes after lateral
      rigid impact traumatic brain injury.
AB  - The model of lateral, rigid impact traumatic brain injury is widely used but
      remains relatively poorly characterized by comparison with fluid percussion
      injury models. Thus, whilst the gross morphological changes that occur over the
      short- and long-term post-injury have been described, more subtle measures of
      neuronal injury and activation, and markers of axonal and glial reactions have
      not been investigated, complicating interpretation of data from this model. To
      address this issue, a variety of neurohistological markers were examined in adult
      male rats which had been subjected to open brain, lateral rigid impact injury. A
      piston device was unilaterally driven 3.0 mm into the somatosensory cortex at a
      speed of 3.2 m/s. Neuronal activation evidenced by Fos-like immunoreactivity
      showed a complex pattern at 3 h after injury which appeared to be related both to
      proximity to the impact site and cortical efferent connectivity. At 24 h after
      injury, acid fuchsin staining demonstrated dying neurons in the margin of the
      injury and in ipsilateral hippocampus and dorsal thalamus. Injured cells
      identified by heat-shock protein immunoreactivity showed a similar distribution.
      Axonal injury demonstrated with 68 kDa neurofilament immunoreactivity was more
      widely distributed. Less axonal damage was found with increasing distance from
      the injury site. At 7 days post-injury, glial fibrillary acidic protein
      immunoreactive astrocytes were prolific in the ipsilateral thalamus, hippocampus
      and striatum and throughout the injured cortex. In general, controlled, lateral
      rigid impact injury provides a more focused injury than is seen with lateral
      fluid percussion which may have implications for the behavioral deficits seen in
      this injury model.

PMID- 9247064
TI  - Stable expression and characterization of the human brain potassium channel
      Kv2.1: blockade by antipsychotic agents.
AB  - We have cloned the cDNA encoding the voltage-dependent K+ channel Kv2.1 from
      human brain (hKv2.1). RNase protection and RT-PCR (reverse transcriptase-PCR)
      experiments reveal abundant Kv2.1 transcripts in human brain with virtually no
      expression detectable in human heart. hKv2.1 has been stably transfected into a
      human glioblastoma cell line, and transformed cells display large, slowly
      activating outward currents. The kinetics, steady-state activation and
      inactivation parameters, and external tetraethylammonium sensitivity were all
      similar to those described previously for hKv2.1 channels transiently expressed
      in Xenopus oocytes or other mammalian cell lines. A number of dopamine receptor
      antagonist/antipsychotic agents were shown to block hKv2.1. Trifluoperizine,
      trifluperidol and pimozide produced time-dependent blockade of hKv2.1 with IC50
      values of approx. 1-2 microM. The diphenylbutylpiperidine fluspirilene was shown
      to be 4-5-fold more potent than the other agents tested inhibiting hKv2.1 current
      with an IC50 value of 297 nM. The block produced by fluspirilene was both time-
      and frequency-dependent. Furthermore, fluspirilene (1 microM) shifted the
      midpotential of the hKv2.1 steady-state inactivation curve by approx. 15 mV in
      the hyperpolarizing direction. These results demonstrate the usefulness of this
      transfection system for the pharmacological characterization of hKv2. 1.
      Fluspirilene proved to be a relatively potent blocker of hKv2.1 and may provide a
      useful starting point for the development of more potent and selective agents
      active against this brain K+ channel.

PMID- 9247065
TI  - Saccule contribution to immediate early gene induction in the gerbil brainstem
      with posterior canal galvanic or hypergravity stimulation.
AB  - Immunolabeling patterns of the immediate early gene-related protein Fos in the
      gerbil brainstem were studied following stimulation of the sacculus by both
      hypergravity and galvanic stimulation. Head-restrained, alert animals were
      exposed to a prolonged (1 h) inertial vector of 2 G (19.6 m/s2) head acceleration
      directed in a dorso-ventral head axis to maximally stimulate the sacculus. Fos
      defined immunoreactivity was quantified, and the results compared to a control
      group. The hypergravity stimulus produced Fos immunolabeling in the dorsomedial
      cell column (dmcc) of the inferior olive independently of other subnuclei.
      Similar dmcc labeling was induced by a 30 min galvanic stimulus of up to -100
      microA applied through a stimulating electrode placed unilaterally on the bony
      labyrinth overlying the posterior canal (PC). The pattern of vestibular afferent
      firing activity induced by this galvanic stimulus was quantified in anesthetized
      gerbils by simultaneously recording from Scarpa's ganglion. Only saccular and PC
      afferent neurons exhibited increases in average firing rates of 200-300%,
      suggesting a pattern of current spread involving only PC and saccular afferent
      neurons at this level of stimulation. These results suggest that alteration in
      saccular afferent firing rates are sufficient to induce Fos-defined genomic
      activation of the dmcc, and lend further evidence to the existence of a
      functional vestibulo-olivary-cerebellar pathway of adaptation to novel gravito
      inertial environments.

PMID- 9247066
TI  - Flexibility of anticipatory postural adjustments revealed by self-paced and
      reaction-time arm movements.
AB  - In standing humans, it is not certain whether anticipatory postural adjustments
      associated with rapid, voluntary elbow flexion movements (focal movements)
      originate as a selection from preset synergies or as the result of specific
      planning of motor commands. We studied these muscle recruitment patterns when the
      same focal movement was made under behavioral conditions of a self-paced task
      (SPT) and a reaction-time task (RTT). While standing still, eight normal subjects
      performed focal movements under the SPT and RTT behavioral conditions and under
      three different biomechanical conditions: (1) unloaded-upright, (2) loaded
      upright (holding a 3800-g metal bar), and (3) unloaded-forward leaning.
      Anticipatory postural adjustments were quantified using the latency and duration
      of electromyographic (EMG) data and the center of pressure (COP) displacement
      data. Postural-kinematic [joint and body center of gravity (COG) motion] data
      were used to quantify the anticipatory postural program's effectiveness at
      preventing postural movement. Focal movement kinematics and associated EMG
      activity differed due to biomechanical but not behavioral (SPT vs. RTT)
      conditions. The maximum and net displacement of the body COG measurements did not
      differ between the behavioral conditions. The amplitude, timing, and net
      movements of lower extremity joints were influenced by the behavioral conditions.
      However, the behavioral conditions significantly affected the phasing (including
      order of activation) and duration of anticipatory postural EMG activity and the
      phasing of COP displacements under certain biomechanical conditions. These
      findings support the theory that anticipatory postural adjustments are planned in
      detail.

PMID- 9247067
TI  - Enhancement of rat trigeminal ganglion neuron responses to piperine in a low-pH
      environment and block by capsazepine.
AB  - Both trigeminal and spinal ganglion neurons show a strong potentiation of
      responses to the irritant capsaicin in an acidic environment. The present study
      revealed that there is also a strong interaction between protons and piperine,
      another vanilloid irritant. We studied the mechanism of the interaction between
      protons and piperine. Whole-cell patch clamp recordings were performed on
      cultured adult rat trigeminal ganglion (TG) neurons voltage-clamped near their
      resting membrane potential (-60 mV). Piperine (10 microM) caused a sustained net
      inward current associated with either an increase or decrease in membrane
      conductance. When protons and piperine were co-applied, the membrane currents
      evoked in piperine-sensitive TG neurons far exceeded the algebraic sum of the
      responses to the two stimuli applied in isolation. Capsazepine blocked the
      response of TG neurons to piperine at both physiological and acidic pH. In the
      presence of capsazepine, responses to the mixture of piperine and protons
      resembled the response to the low pH stimulus applied alone. Capsazepine had no
      effect on the sustained proton-induced current. These findings suggest that
      protons enhance the piperine current by altering the vanilloid receptor/channel
      complex or increasing the length constant of the space clamp.

PMID- 9247068
TI  - Expression of the proprotein convertases PC1 and PC2 mRNAs in thyrotropin
      releasing hormone neurons of the rat paraventricular nucleus of hypothalamus.
AB  - PC1 and PC2 are subtilisin-like processing enzymes capable of cleaving
      thyrotropin releasing hormone (TRH) precursor (pro-TRH) at paired basic residues
      in vitro. In the paraventricular nucleus of the hypothalamus (PVN), pro-TRH is
      synthesized to control adenohypophysial thyrotropin and prolactin release.
      Biochemical and immunological approaches have shown that in the hypothalamus, pro
      TRH is extensively cleaved at pairs of basic amino acids. We quantified, by two
      different approaches, in situ hybridization (ISH) on consecutive cryostat
      sections or double label ISH, the proportion of PVN TRH neurons containing either
      PC1 or PC2 mRNAs. Both techniques gave similar results: PC2 mRNA was present in
      60-70% of TRH neurons, and PC1 mRNA in 37-46%. Values were similar in the
      anterior and medial parts of the parvocellular PVN. TRH neurons containing either
      PC1 or PC2 mRNA were found throughout the areas containing TRH cells without any
      evidence of anatomical segregation. These results suggest a biochemical
      heterogeneity in PVN TRH biosynthetic machinery.

PMID- 9247069
TI  - Identification and characterisation of 2-[125I]iodomelatonin binding and Mel1a
      melatonin receptor expression in the human fetal leptomeninges.
AB  - Melatonin binding sites were identified over the leptomeninges surrounding the
      human fetal brain using quantitative in vitro autoradiography and the melatonin
      agonist, 2-[125I]iodomelatonin. Binding was found to be saturable and of high
      affinity (dissociation constant (Kd) = 54 pM and maximal theoretical binding
      (Bmax) = 13 fmol/mg protein), and inhibited by guanosine-5'-o-(3
      thiotriphosphate) (GTPgammaS) suggesting that these binding sites represent G
      protein-coupled melatonin receptors. RT-PCR performed on mRNA isolated from the
      human fetal leptomeninges detected expression of the G protein-coupled melatonin
      receptor Mel1a, but not Mel1b. In situ hybridisation confirmed the localisation
      of Mel1a mRNA transcripts over the leptomeninges of the fetal brain. The
      identification of 2-[125I]iodomelatonin and Mel1a melatonin receptor expression
      in the fetal leptomeninges implies that melatonin may play a role in the early
      growth and development of the human brain.

PMID- 9247070
TI  - Postsynaptic blockade of inhibitory postsynaptic currents by plasmin in CA1
      pyramidal cells of rat hippocampus.
AB  - We have shown previously that plasmin facilitated the generation of long-term
      potentiation (LTP) in CA1 and dentate region of rat hippocampus. In the present
      study, we investigated the effects of plasmin on postsynaptic currents in CA1
      pyramidal neurons of rat hippocampal slices. Plasmin (100 nM) had no effect on
      NMDA nor on non-NMDA receptor-mediated excitatory postsynaptic currents. However,
      plasmin significantly decreased GABA(A) receptor-mediated inhibitory postsynaptic
      currents. This effect of plasmin disappeared when intracellular Ca2+ was strongly
      chelated with BAPTA. Furthermore, plasmin attenuated the GABA-induced currents in
      CA1 pyramidal cells. These results suggest that the STP-enhancing effect of
      plasmin is due to a blockade of postsynaptic GABA(A) responses and that an
      increase in intracellular Ca2+ by plasmin may be involved in its mechanism.

PMID- 9247071
TI  - DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the
      ventral pallidum.
AB  - Serotonin (5-HT)2A receptors are known to be involved in prepulse inhibition of
      the startle response (PPI), a measure of sensorimotor inhibition that is
      deficient in schizophrenia, Huntington's disease, and obsessive compulsive
      disorder. In the present studies, the localization of the 5-HT2A receptors
      responsible for modulating PPI was investigated using central injections of the
      hallucinogenic 5-HT2 agonist DOI and the novel 5-HT2A antagonist MDL 100,907. 5
      HT2A receptors are densely localized in the nucleus accumbens (NAC) and the
      ventral pallidum (VP), areas known to be important components of neural circuitry
      that mediates the ventral forebrain modulation of PPI. In the present studies, it
      was found that the infusion of DOI (0.0-5.0 microg/0.5 microl) into the VP
      disrupted PPI without having effects on startle reactivity. In contrast, similar
      infusions into the NAC had no effect on PPI or startle reactivity. The infusion
      of MDL 100,907 into the VP was found to increase PPI by itself and to attenuate
      the PPI-disruptive effects of systemically administered DOI. It is concluded that
      5-HT2A receptors within the VP are important for the modulation of PPI,
      presumably through interactions at intrinsic GABAergic or cholinergic
      interneurons.

PMID- 9247072
TI  - Regulation of GABA release via NMDA and 5-HT1A receptors in guinea pig dentate
      gyrus.
AB  - The regulation by N-methyl-D-aspartate (NMDA) and 5-HT1A receptors of the
      endogenous gamma-aminobutyric acid (GABA) release was investigated in slices of
      the guinea pig dentate gyrus. The release of GABA was increased in a
      concentration-dependent fashion by NMDA. The release of GABA evoked by NMDA was
      Ca2+-dependent, tetrodotoxin-resistant, Mg2+-sensitive and inhibited by MK-801, a
      selective non-competitive NMDA receptor antagonist. These results suggest that
      the NMDA receptor present on GABAergic neurons is involved in the stimulatory
      regulation of GABA release. The release of GABA was increased concentration
      dependently by NAN-190, a 5-HT1A receptor antagonist, but was not affected by 8
      OH-DPAT, a 5-HT1A receptor agonist. The release of GABA evoked by NAN-190 was
      Ca2+-dependent, tetrodotoxin-resistant and inhibited by 8-OH-DPAT. These results
      suggest that the 5-HT1A receptor present on GABAergic neurons is involved in the
      inhibitory regulation of GABA release. The release of GABA evoked by NMDA from
      the dentate gyrus was inhibited by pretreatment with 8-OH-DPAT. The release of
      GABA evoked by NAN-190 was inhibited by pretreatment with MK-801. The release of
      GABA evoked by NMDA from the dentate gyrus was augmented by the concurrent
      application of NAN-190. Taken together, the results indicate that the NMDA
      receptor and the 5-HT1A receptor, which are both located on GABAergic neurons in
      the guinea pig dentate gyrus, exert stimulatory and inhibitory regulation of
      neuronal GABA release, respectively.

PMID- 9247073
TI  - The involvement of nitric oxide in the secretion of beta-endorphin from the
      pituitary intermediate lobe of the rat.
AB  - Nitric oxide (NO) generated by the enzyme nitric oxide synthase (NOS) has been
      implicated in the regulation of a variety of endocrine functions. A number of
      biochemical and anatomical studies have demonstrated the presence of neuronal NOS
      (nNOS) in the neuroendocrine axis and have shown significant effects of NO on the
      release of hypothalamic and pituitary hormones. Using a C-terminal directed
      peptide antibody that is specific for nNOS we have found a predominance of nNOS
      in the neural lobe of the pituitary and in a single layer of epithelial cells,
      possibly a remnant of Rathke's pouch that form a border between the intermediate
      lobe and the anterior lobe. Furthermore, we have examined the effect of sodium
      nitroprusside (SNP), a donor of NO on the secretion of beta-endorphin (beta-EP)
      from the isolated neuro-intermediate lobe (NIL) of the rat and cultured rat
      melanotrophs. It was shown that in explant cultures of intact neuro-intermediate
      lobes, SNP (100 microM) was able to cause an inhibition of beta-EP secretion. In
      the presence of sulpiride (10 microM), a dopamine D2-receptor antagonist, there
      was a partial reversal of the SNP effect. On the other hand SNP did not affect
      beta-EP secretion in primary cultures of melanotrophs that no longer possessed
      any innervation. Taken together these data suggest that NO has an indirect
      inhibitory effect on the secretion of beta-EP by the intermediate lobe via the
      release of dopamine.

PMID- 9247074
TI  - Regulation of synaptic plasticity by mGluR1 studied in vivo in mGluR1 mutant
      mice.
AB  - The role of the metabotropic glutamate receptor 1 (mGluR1) in synaptic plasticity
      was investigated in vivo in the intact hippocampus of mutant mice lacking this
      receptor. In a previous study we showed reduced long-term potentiation (LTP) in
      the dentate gyrus of mGluR1 -/- mice in vivo, but not when LTP was studied in a
      slice preparation. A possible explanation of this difference is that dentate
      neurons receive more inhibitory synaptic drive in vivo than in slice preparation
      where many inhibitory axon collaterals are lost. We report here that another form
      of synaptic plasticity, paired-pulse depression of the population spike, is also
      abnormal in the dentate gyrus of mGluR1-deficient mice when tested in vivo. In
      wild-type mice, stimulation of the medial perforant path produced paired-pulse
      depression of inter-pulse intervals (IPIs) up to 30 ms. Mutant mGluR1, on the
      other hand, showed a significantly longer IPI depression, up to 50 ms. Paired
      pulse depression results from the activation of inhibitory interneurons. The
      GABA(B) agonist baclofen, acting presynaptically on the GABA interneurons,
      attenuated paired-pulse depression and allowed for a normal and stable LTP in
      mGluR1 mutant mice. These findings suggest an indirect role for mGluR1 in
      synaptic plasticity via a regulation of GABA inhibition.

PMID- 9247075
TI  - Long-term effects of cysteamine on cognitive and locomotor behavior in rats:
      relationship to hippocampal glial pathology and somatostatin levels.
AB  - Peroxidase-positive astrocytic inclusions, derived from effete, iron-laden
      mitochondria, accumulate in the rat hippocampus, striatum and other subcortical
      brain regions as a function of advancing age. The sulfhydryl agent, cysteamine
      (CSH), accelerates the appearance of this senescent glial phenotype both in
      primary astrocyte cultures and in the aging subcortical brain in situ. Earlier
      experiments have shown that short-term administration of CSH results in
      reversible depletion of brain somatostatin (SS) levels, cognitive deficits and
      decreases in locomotor activity. In the present study, we tested spatial
      learning/memory and motor functioning in rats at 4-5 weeks following cessation of
      chronic (6 week) CSH treatment to determine whether behavioral deficits may be
      associated with gliopathic changes within the dorsal hippocampus distinct from
      the behavioral abnormalities accruing to the immediate effects of the drug. CSH
      treated rats displayed significantly impaired performance in the Morris water
      maze 4-5 weeks following termination of prolonged CSH treatment. In contrast,
      locomotor activity was not affected in this experimental paradigm. CSH-treated
      animals exhibited significantly higher numbers of peroxidase-positive astrocyte
      granules as well as total numbers of GFAP-positive astrocytes in the CA1 sector
      of the dorsal hippocampus relative to saline-treated controls. In the hilus of
      the dentate gyrus, numbers of both peroxidase-positive glial inclusions and
      astrocytes were unaffected by CSH exposure. At 5 weeks following cessation of CSH
      treatment, SS levels in the hippocampus and hypothalamus (but not cerebral
      cortex) were elevated relative to those of saline-treated controls. Our results
      indicate that chronic CSH exposure induces senescence-like changes in CA1
      astrocytes which are associated with deficits in cognitive, but not locomotor,
      behavior and elevated levels of hippocampal and hypothalamic SS. Pathological
      glial-neuronal interactions within the hippocampus and other subcortical brain
      regions may play an important role in the cognitive decline observed during
      normal senescence and in aging-related neurodegenerative disorders.

PMID- 9247076
TI  - Parvalbumin- and calbindin-containing neurons express c-fos protein in primary
      and secondary (mirror) epileptic foci of the rat neocortex.
AB  - The present experiments aimed at the description and further immunocytochemical
      characterization of activated neocortical neurons expressing the c-fos gene.
      Focal seizures were induced by the topical application of isotonic, isohydric 4
      aminopyridine solution to the frontal neocortex of adult anesthetized Wistar
      rats. The EEG of both hemispheres was recorded from the surface of the skull. The
      animals were perfused with fixative, coronal plane vibratome sections were cut
      and stained with cocktails containing polyclonal c-fos and monoclonal calbindin
      or parvalbumin antibodies. The polyclonal c-fos antibody was tested with Western
      blotting and the diffusion of 4-aminopyridine investigated with autoradiography
      of [3H]4-aminopyridine. The c-fos protein was detected in every layer of the
      neocortex (primary focus) and in some allocortical areas of the treated
      hemisphere. Scattered immunostained nuclei were observed in layers II, III, IV
      and VI of the contralateral neocortex (mirror focus). Several parvalbumin- and
      calbindin-positive neurons contained the c-fos protein in both foci. The medium
      sized non-pyramidal parvalbumin neurons were found in layers II-IV and VI of the
      neocortex and in stratum multiforme of the prepiriform cortex. The c-fos protein
      was colocalized with calbindin mainly in layers II and III in small and medium
      sized non-pyramidal neurons. The results prove that focal epileptiform activity
      of the neocortex activates diverse inhibitory neuronal populations. As concluded,
      the inhibitory control is probably more effective in the contralateral hemisphere
      (mirror focus) than on the side of 4-APY treatment (primary focus).

PMID- 9247077
TI  - Starvation and dehydration attenuate CNS oxygen toxicity in rats.
AB  - We tested the effect of moderate food or water deprivation and a combination of
      the two on sensitivity to hyperoxia-induced seizures in rats. Seventy rats with
      chronic cortical electrodes were exposed to seven experimental protocols:
      starvation, dehydration or a combination of both for 24 or 36 h, prior to
      exposure to 0.5 Mp(a)O2. Blood glucose and hematocrit were measured before and
      after exposure to hyperbaric oxygen (HBO). Starvation and dehydration
      significantly prolonged the latent period to the onset of hyperoxia-induced
      seizures (P < 0.05 in the Tukey test), in a dose-related manner. Our results
      suggest that deprivation of food or water, prior to exposure to HBO, may postpone
      the development of hyperoxia-induced seizures.

PMID- 9247078
TI  - 2-Phenylaminoadenosine stimulates dopamine synthesis in rat forebrain in vitro
      and in vivo via adenosine A2 receptors.
AB  - The adenosine agonist 2-phenylaminoadenosine (PAD) stimulated tyrosine
      hydroxylase activity in rat striatum in vitro. This effect was selectively
      blocked by the A2 antagonist 8-chlorostyrylcaffeine (CSC), suggesting an A2
      receptor-mediated mechanism. PAD also produced a corresponding increase in
      striatal adenylyl cyclase activity. Using an in vivo model that measures
      presynaptic effects of drugs at dopamine nerve terminals, intracerebroventricular
      administration of PAD to rats stimulated tyrosine hydroxylase activity in
      striatum in a manner that was selectively blocked by CSC. These results suggest
      that PAD stimulates adenylyl cyclase and tyrosine hydroxylase activity, with a
      corresponding increase in dopamine synthesis, by activation of presynaptic A2
      type receptors in mammalian forebrain.

PMID- 9247079
TI  - Nitric oxide synthase in developing retinas and after optic tract section.
AB  - We compared the pattern of nitric oxide synthase (NOS) immunoreactivity in
      retinas of rats during normal development and after unilateral transection of the
      optic tract at postnatal day 7. NOS was first detected in the second postnatal
      week in the inner nuclear and inner plexiform layers. There was no detectable
      difference in the overall pattern of immunoreactivity between normal retinas and
      retinas with severe loss of ganglion cells due to the lesion. We suggest that NOS
      may have a role in synaptic and vascular development in the inner retina, but is
      unlikely to play a major role in normal physiological retinal ganglion cell death
      or axotomy-induced cell death.

PMID- 9247080
TI  - Regional changes in beta1 thyroid hormone receptor immunoreactivity in rat brain
      after thyroidectomy.
AB  - Quantitative [125I]protein G-based immunohistochemistry was used to map the
      distribution of beta1 thyroid hormone receptor (TRbeta1) in normal and
      thyroidectomized adult rat brain, using a previously characterized polyclonal
      antibody. The distribution of TRbeta1-like immunoreactivity in normal brain was
      largely but not perfectly concordant with previous accounts of TRbeta1 mRNA
      distribution in rat brain. Thyroidectomy resulted in increased immunolabeling in
      most brain regions (mean increase: 14%, range: -4% to +25%), with statistically
      significant effects being observed in 9 of the 36 brain regions examined. Brain
      regions showing the most pronounced effects included the habenular nucleus
      (+22%), the oriens layer of the hippocampal CA3 region (+24%), and the lateral
      geniculate nucleus of the thalamus (+23%). These results demonstrate that the
      TRbeta1 protein in brain is capable of plastic changes in response to adult-onset
      alterations in TH levels. The observed pattern of brain regional receptor changes
      following thyroidectomy may provide clues for functional effects of thyroid
      function alterations in adults.

PMID- 9247082
TI  - Dopamine regulation of extracellular glutamate in the nucleus accumbens.
AB  - The capacity of dopamine to alter extracellular glutamate in the nucleus
      accumbens was examined by passing 1, 10 and 100 microM of amphetamine, the D(2/3)
      agonist, quinpirole, or the D1 agonist, SKF-82958 through a microdialysis probe.
      It was found that amphetamine and quinpirole produced a dose-dependent reduction
      in the basal levels of extracellular glutamate, while SKF-82958 was without
      significant effect. The capacity of the D1 antagonist, SCH-23390 (1.0 mg/kg,
      i.p.) or the D2 antagonist, sulpiride (10 mg/kg, i.p.) to block the reduction in
      extracellular glutamate by amphetamine (100 microM) was examined. Both SCH-23390
      and sulpiride prevented the reduction in extracellular glutamate by amphetamine.
      The data indicate that, similar to the striatum, glutamate release in the nucleus
      accumbens is modulated by presynaptic dopamine receptors.

PMID- 9247081
TI  - Oxidized low density lipoprotein caused CNS neuron cell death.
AB  - Death induced by oxidized low density lipoproteins (oxLDL) to embryonic CNS
      neuronal and neuroblastoma cells was investigated. Cell damage and viability were
      evaluated by LDH leakage and the MTT method, respectively. Dose- and time
      dependent degeneration of neurons occurred after oxLDL (1-100 microg/ml)
      treatment but was absent after native low density lipoproteins (LDL). This
      degeneration was mediated, in part, by apoptosis because increased TUNEL and
      Hoechst dye-positive staining was observed. These effects occurred in the absence
      of microglia. However, DNA degradation was not detected. The cytotoxicity was
      attenuated by pre-treatment with antioxidants. These results suggest that
      oxidation by oxLDL may be important in neurocytotoxicity in the brain.

PMID- 9247083
TI  - Palmitoyl-protein thioesterase deficiency in fibroblasts of individuals with
      infantile neuronal ceroid lipofuscinosis and I-cell disease.
AB  - Mutations in the gene encoding a recently described lysosomal enzyme, palmitoyl
      protein thioesterase (PPT), have recently been shown to result in the
      neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL).
      Reduced palmitoyl-protein thioesterase enzyme has been demonstrated previously in
      INCL brain and immortalized lymphoblasts. In the current paper, we demonstrate
      that: (1) PPT can be detected by immunoblotting and enzyme activity assays in
      normal human skin fibroblasts; (2) INCL fibroblasts are deficient in PPT
      activity; (3) I-cell disease fibroblasts show markedly reduced intracellular
      levels of PPT but markedly increased levels of PPT in cell culture medium. These
      data establish that PPT is transported to lysosomes via the lysosomal
      enzyme:lysosomal enzyme receptor phosphomannosyl recognition system under normal
      physiological conditions and provide the basis for a useful clinical assay for
      INCL.

PMID- 9247084
TI  - Sequence and structure of the human OXA1L gene and its upstream elements.
AB  - The genes encoding proteins involved in respiratory chain assembly represent
      candidate genes for nuclearly-encoded multiple respiratory chain deficiency.
      Using the long PCR amplification procedure, we have characterized the
      organization and complete sequence of OXA1L, a gene involved in the assembly of
      several complexes of the mitochondrial respiratory chain. The OXA1L gene (5 kb)
      is composed of 10 exons and 9 introns and contains a 24 N-terminal amino-acid
      stretch is characteristic of a mitochondrial presequence. The screening of OXA1L
      mutation in patients with multiple respiratory chain deficiency is now feasible.

PMID- 9247085
TI  - Molecular cloning of seprase: a serine integral membrane protease from human
      melanoma.
AB  - Seprase is a homodimeric 170 kDa integral membrane gelatinase whose expression
      correlates with the invasiveness of the human melanoma cell line LOX. Here, we
      report the molecular cloning of a cDNA that encodes the 97 kDa subunit of
      seprase. Its deduced amino acid sequence predicts a type II integral membrane
      protein with a cytoplasmic tail of 6 amino acids, followed by a transmembrane
      domain of 20 amino acids and an extracellular domain of 734 amino acids. The
      carboxyl terminus contains a putative catalytic region (approximately 200 amino
      acids) which is homologous (68% identity) to that of the nonclassical serine
      protease dipeptidyl peptidase IV (DPPIV). The conserved serine protease motif G-X
      S-X-G is present as G-W-S-Y-G. However, sequence analysis of seprase cDNA from
      LOX and other cell lines strongly suggests that seprase and human fibroblast
      activation protein alpha (FAP alpha) are products of the same gene. We propose
      that seprase/FAP alpha and DPPIV represent a new subfamily of serine integral
      membrane proteases (SIMP).

PMID- 9247086
TI  - Cloning and characterization of the rat p130, a member of the retinoblastoma gene
      family.
AB  - A cDNA clone encoding rat p130, a member of the retinoblastoma (Rb) gene family,
      was isolated based on the sequence homology of the E1A-binding domain. The 4.87
      kb cDNA contained an 1135-amino acid open reading frame with high homologies to
      the human and mouse p130 and a partial homology to the pRb protein. p130 showed
      difference in distribution of potential phosphorylation sites from pRb in the N
      terminal and the B pocket regions. p130 mRNA was detected in most rat tissues.
      The p130 gene was mapped to rat chromosome 19p11-13 by fluorescence in situ
      hybridization.

PMID- 9247087
TI  - Structure and differential target sensitivity of the stimulable cytotoxic complex
      from hemolymph of the Mediterranean mussel Mytilus galloprovincialis.
AB  - A cytotoxic protein complex of 320 kDA was isolated from dialyzed plasma of the
      edible mussel, Mytilus galloprovincialis. Constituted by the assembly of several
      different proteins, the complex exhibits selective killing against eukaryotic
      cells, including erythrocytes, mouse tumor cells and protozoan parasites. High
      variability, which was not correlated with protein concentration, suggested that
      the immune response of naive mussels was in various stages of activation.
      Stimulation assays by different treatments in vivo resulted in significant
      increases in the activity of the plasma suggesting that cytotoxic complexes are
      involved in immune defense. Lytic activity appears to involve binding of
      cytotoxic complexes onto target cell membranes and the formation of transmembrane
      pores. This research provides more evidence that the innate immune system of
      invertebrates involves large cytotoxic proteins with a broad range of recognitive
      specificities in addition to small antibacterial, antifungal peptides.

PMID- 9247088
TI  - Severe hypoxemia in the absence of blood loss depresses hepatocellular function
      and up-regulates IL-6 and PGE2.
AB  - Although hepatocellular function is depressed early after trauma and hemorrhage
      (which are associated with low flow conditions and tissue hypoxemia), it remains
      unknown whether hypoxemia without blood loss, produces hepatocellular dysfunction
      and, if so, whether IL-6 and PGE2 are associated with this dysfunction. To study
      this, rats were placed in a plastic box which was flushed with a gas mixture
      containing 6.3% O2:93.7% N2 or room air for 60 min, followed by their return to
      room air. At 0 and 4 h after hypoxemia, hepatocellular function (i.e., maximum
      velocity of indocyanine green clearance (Vmax) and the efficiency of the
      transport (Km)) was measured using an in vivo hemoreflectometer. Cardiac output
      was assessed by dye dilution technique. Tissue microvascular blood flow was
      determined by laser Doppler flowmetry. Plasma IL-6 and PGE2 were measured by
      bioassay and radioimmunoassay, respectively. The results indicate that hypoxemia
      produced a depression in hepatocellular function (i.e., decreased Vmax by 44-50%
      and Km by 55-68%) despite stable cardiac output and hepatic microcirculation at 0
      and 4 h after hypoxemia. Moreover, hypoxemia resulted in a significant increase
      in plasma IL-6 (by 372%-389%) as well as PGE2 (by 38% at 0 h post-hypoxemia).
      Thus, hypoxemia observed after trauma and hemorrhagic shock appears to be
      responsible for producing hepatocellular dysfunction possibly through the up
      regulation of IL-6 and PGE2. In view of this, long-lasting hypoxemia in trauma
      victims should be avoided, perhaps by early intubation and ventilation so that
      the potential additional proinflammatory cytokine and PGE2 release can be
      prevented.

PMID- 9247089
TI  - EPR investigations of the iron domain in neuromelanin.
AB  - The interactions between iron and neuromelanin (NM) have been studied by means of
      EPR spectroscopy. The variable temperature EPR spectral features of a specimen of
      NM extracted from normal human midbrains clearly indicate that iron is present as
      polynuclear oxy-hydroxy ferric aggregates as well as isolated Fe(III) centres.
      Ferric oxy-hydroxy phases are typical of the iron storage proteins ferritin and
      hemosiderin, but the comparison of the variable temperature EPR spectra of
      ferritin and NM highlights significant differences between the two iron(III)oxy
      hydroxy domains. Moreover, further investigations on melanin models synthesised
      in the presence of either ferritin or a ferric salt as iron sources suggest that
      the same pathway of formation and inclusion of the polynuclear iron oxide is
      operating in NM and in the model systems, whatever is the source of iron.

PMID- 9247090
TI  - NADH stimulates endogenous dopamine biosynthesis by enhancing the recycling of
      tetrahydrobiopterin in rat phaeochromocytoma cells.
AB  - Treatment of Parkinson patients with L-DOPA (3,4-dihydroxy-L-phenylalanine) leads
      to endproduct inhibition of tyrosine hydroxylase, the key enzyme in dopamine
      biosynthesis and the enzyme needing tetrahydrobiopterin and iron as cofactors. To
      overcome this problem an alternative treatment was investigated which attempted
      to stimulate endogenous dopamine biosynthesis. Incubation of rat PC 12 cells with
      NADH (beta-nicotinamide adeninedinucleotide) leads to increased dopamine
      production. We investigated the possibility that this increase of dopamine
      biosynthesis was due to stimulation of quinonoid dihydropteridine reductase, the
      enzyme which recycles the inactive dihydrobiopterin to the active
      tetrahydrobiopterin. The experiments showed that whereas NADH is able to increase
      dopamine production in PC 12 cells (rat phaeochromocytoma cells, clone PC 12) up
      to three-fold, no influence is exerted by NADH on pteridine metabolism; neither
      are tetrahydrobiopterin concentrations nor the de novo-biosynthesis of pteridines
      from guanosine triphosphate altered by NADH. Further no influence of NADH on
      protein de novo synthesis of quinonoid dihydropteridine reductase was observed.
      However, NADH was able to directly increase the catalytic activity of this
      enzyme. Our results suggest that the stimulation of dopamine biosynthesis by NADH
      is due to more rapid regeneration of quinonoid dihydrobiopterin to
      tetrahydrobiopterin.

PMID- 9247091
TI  - Late-infantile ceroid-lipofuscinosis: lysine methylation of mitochondrial ATP
      synthase subunit c from lysosomal storage bodies.
AB  - Late-infantile ceroid-lipofuscinosis is a fatal autosomal recessively inherited
      disease characterized by massive accumulations of lysosomal storage bodies in
      many tissues. A major constituent of the storage bodies is the subunit c protein
      of mitochondrial ATP synthase. Juvenile ceroid-lipofuscinosis, a disease that is
      similar to but genetically distinct from the late-infantile disorder, also
      involves lysosomal accumulation of the subunit c protein. In the juvenile
      disease, the stored form of the protein contains an epsilon-N-trimethyllysine
      (TML) residue at position 43. Analyses were performed to determine whether
      subunit c protein stored in the late-infantile disease is also trimethylated at
      lysine residue 43. Amino acid composition analysis of the subunit c protein
      stored in brains from subjects with the late-infantile disease indicated that one
      of the two lysine residues in the protein is trimethylated. Data from molecular
      mass analysis of the protein was consistent with the presence of three methyl
      groups not present in the unmodified protein. The TML in the storage body subunit
      c protein was found by amino acid sequence analysis to occur exclusively at
      residue 43. The lysine at this position in the stored protein was completely
      methylated. Recent studies suggest that the subunit c protein from normal
      mitochondria may also have the same amino acid modification. Thus, it appears
      that specific methylation of lysine residue 43 of mitochondrial ATP synthase
      subunit c is probably a normal post-translational modification, and that the
      lysosomal storage of this protein in late-infantile, as well as in juvenile
      ceroid-lipofuscinosis, does not result from a defect in its methylation.

PMID- 9247092
TI  - Calcium and protein kinase C play a significant role in response to Shigella
      toxin in rabbit ileum both in vivo and in vitro.
AB  - The role of second messengers in Shigella toxin (STx) induced fluid secretion in
      rabbit ileum was evaluated. In vivo and in vitro studies were carried out in
      presence or absence of following modulators: Ca2+ ionophore A23187 (15 microM), l
      verapamil (200 microM), phorbol-12-myristate-13-acetate (PMA, 200 ng), 1-(5
      isoquinolinyl-sulphonyl)-2-methyl-piperazine (H-7, 15 microg) and indomethacin
      (20 microM). In in vivo studies, the fluid accumulation into rabbit ileal loops
      in response to STx was measured in presence or absence of these modulators. In in
      vitro studies, unidirectional fluxes of Na+ and Cl- were carried out in presence
      or absence of these modulators. The addition of Ca2+ ionophore A23187 along with
      STx further increases the amount of fluid already induced by STx. Whereas the
      presence of l-verapamil along with STx did not decrease the amount of fluid
      induced by STx. In vitro findings were in consonance with the in vivo studies. A
      significant increase in inositol triphosphate (IP3) levels was observed in
      enterocytes isolated from STx treated rabbit ileum. The addition of PMA into
      rabbit ileal loops in presence of STx mimicked the effect of STx while the
      presence of H-7 reversed the secretion caused by STx to absorption. Similar
      results were obtained while determining unidirectional fluxes of Na+ and Cl- in
      presence of PMA and also with H-7. A significant increase in PKC levels was
      observed in the membrane fraction of enterocytes isolated from STx treated rabbit
      ileum as compared to control. Further a marked decrease in PKC levels was
      observed in the presence of H-7 in membrane fraction of enterocytes isolated from
      STx treated rabbit ileum. The addition of indomethacin into rabbit ileal loops
      reversed the secretion (caused by STx) to absorption. In vitro findings were in
      consonance with in vivo studies. Besides, there was a significant increase in PG
      E levels in enterocytes isolated from STx treated rabbit ileum as compared to
      control. These findings suggested that STx induced enteritis involves the role of
      PKC, intracellular calcium stores and prostaglandins. The extracellular calcium
      pool probably does not play a significant role in this process.

PMID- 9247093
TI  - Cloning of the gp63 surface protease of Leishmania infantum. Differential post
      translational modifications correlated with different infective forms.
AB  - The Leishmania cell surface virulence factor gp63 is a protease family that plays
      an important role in the survival of the parasite protozoon into the host
      macrophages. We have cloned and characterised the gp63 gene from L. infantum. The
      sequence analysis of the gene indicates the existence of a high degree of
      conservation with the other old world species L. major and L. donovani. The
      similarity is lower with new world species with the exception of L. chagasi which
      shows a strikingly high percentage of identity (99-100%). In L. infantum the gp63
      gene expresses two polypeptides of 58 and 60 kDa, respectively, which show a
      similar proteolytic activity. The 60 kDa polypeptide is expressed during the
      whole life cycle of the promastigote form of the parasite with a moderate
      increase at the stationary phase of growth while the 58 kDa product, although
      slightly present in the logarithmic phase, notable increases its expression
      during the highly infectious stationary phase. RNA analysis showed that the
      presence in L. chagasi of these two polypeptides correlates with two RNA
      molecules and with the degree of parasite infectivity, whereas in the case of L.
      infantum a single 3 kb messenger RNA is detected through the whole promastigote
      life cycle. Our data indicate that in L. infantum, the differences in gene
      expression of the gp63 protease family according to parasite phase of growth seem
      to be due to a differential pattern of glycosilation of the polypeptides which
      correlates with the different infective forms of the promastigote form of the
      parasite.

PMID- 9247094
TI  - Sequestration of coenzyme A by the industrial surfactant, Toximul MP8. A possible
      role in the inhibition of fatty-acid beta-oxidation in a surfactant/influenza B
      virus mouse model for acute hepatic encephalopathy.
AB  - We have investigated the mechanistic basis of our recent observation that
      exposing young mice to an industrial surfactant potentiates the inhibition of
      fatty-acid beta-oxidation that occurs with subsequent virus infection (Murphy et
      al., Biochim. Biophys. Acta 1315, 208-216, 1996). In our mouse model for acute
      hepatic encephalopathy (AHE), neonatal mice were painted on their abdomens from
      birth to postnatal day 12 with nontoxic amounts of the industrial surfactant,
      Toximul MP8 (Tox), and then infected with a sublethal dose (LD30) of mouse
      adapted human Influenza B (Lee) virus (FluB). Mortality in mice treated with Tox
      + FluB was significantly higher than that in mice treated with FluB alone. In
      vitro assays of hepatic beta-oxidation of [1-(14)C]palmitic and [1-(14)C]octanoic
      acids in the presence or absence of exogenous coenzyme A (CoA) indicated that Tox
      mediated inhibition of oxidation was masked when CoA was added to the assays.
      FluB also inhibited beta-oxidation by 20-30%, however this effect was independent
      of exogenous CoA which suggested that it involved a different mechanism. Tox
      mediated potentiation of the inhibitory effect was most obvious (> 80%
      inhibition) when assays were done without added CoA. Analysis of hepatic CoA and
      its esters indicated that levels of both free CoA and acetyl-CoA were
      significantly lower in mice that were painted with Tox for 12 days. Tox-dependent
      reductions of acetyl-CoA were transient and returned to normal values after
      cessation of painting, whereas those of CoA persisted. FluB infection alone
      significantly reduced hepatic acetyl-CoA and the magnitude of this reduction (>
      30%) was not affected by pre-exposing the mice to Tox. Relative to control mice,
      levels of acid insoluble acyl-CoA esters were elevated significantly in FluB and
      Tox + FluB treated mice. Activation of both [1-(14)C]palmitic and [1
      (14)C]octanoic acids was reduced in Tox-exposed mice at experimental day 12, but
      only when exogenous CoA was not included in the assay media; this effect appeared
      to persist after cessation of painting. Collectively, these data support the
      concept that Tox and FluB have independent effects on hepatic CoA metabolism that
      are associated with abnormalities in fatty-acid beta-oxidation. However, these do
      not fully explain the synergistic effect of the virus and chemical on beta
      oxidation inhibition, which is a candidate co-mechanism for potentiation of
      mortality in this mouse model of AHE.

PMID- 9247095
TI  - Mosquito midgut glycoproteins and recognition sites for malaria parasites.
AB  - Midgut glycoproteins of the malaria vector Anopheles tessellatus were partially
      characterised by gel electrophoresis and lectin binding. Specific binding to
      wheat germ agglutinin (WGA) and Concanavalin A (Con A) indicated the presence of
      N-linked core oligosaccharides in many proteins. Rabbit antibodies were produced
      against wheat germ agglutinin binding proteins (WGABP). These antibodies also
      recognised distinct proteins in the peritrophic membrane which is secreted into
      the midgut to enclose a bloodmeal. Rabbit anti-WGABP antibodies ingested in a
      bloodmeal containing infective gametocytes of the human malaria parasites
      Plasmodium falciparum and P. vivax tended to reduce infectivity of the parasites
      to vector mosquitoes. Chitotriose added to a bloodmeal also inhibited parasite
      development in the mosquito. The results are consistent with a hypothesis that N
      acetyl glucosamine residues in mosquito midgut glycoproteins and/or midgut chitin
      and proteoglycan function as recognition sites for malaria parasites.

PMID- 9247097
TI  - On the importance of sensitivity to the dose-effect relationship in chemotherapy.
AB  - The dose effect relationship of cytostatics is discussed from a theoretical point
      of view. Assuming tumour cell sensitivity as a continuum and an exponential
      distribution of cell probability density as a function of sensitivity the 'log
      kill' concept has been extended to a model describing the relation between dose
      and effect in malignant tumours. The model is based on only 3 parameters: The
      ratio between maximum and minimum sensitivity, the ratio between maximum and
      minimum cell probability density according to sensitivity and finally the product
      of dose and (minimum) sensitivity. The model demonstrates that the fractional
      tumour reduction intended is of major importance for the resulting curves. Dose
      effect curves describing a small fractional cell kill (0.5) are much steeper than
      curves describing a high one (to 10(-3)). Possible clinical implications of the
      model are discussed.

PMID- 9247096
TI  - Ki-67, p53, Er-receptors, ploidy and S-phase as prognostic factors in T1 node
      negative breast cancer.
AB  - The prognostic value of Ki-67, p53 and ER immunohistochemical labelling and flow
      cytometric S-phase fraction and ploidy was evaluated in 212 pT1N0M0 breast
      carcinomas. The mean follow-up time was 8.3 years. Patients with breast
      carcinomas with high Ki-67 expression (> or = 10%) had a less favourable disease
      free survival than those with low Ki-67 expression (< 10%) (p = 0.008). A
      positive p53 staining and high SPF were associated with a less favourable disease
      free survival although it did not reach statistical significance. The subset of
      patients with ER negative, Ki-67 > or = 10% and p53 > or = 20% tumours, had a
      shorter disease-free survival compared with that of all the other patients (p =
      0.03). We conclude that the potential value of Ki-67 labelling for prognostic
      evaluation of T1N0M0 breast carcinoma is good.

PMID- 9247098
TI  - Angiogenic and angiostatic microenvironment in tumors--role of gangliosides.
AB  - Gangliosides are important components of the cell membrane that are usually shed
      in the surrounding microenvironment by neoplastic cells. Gangliosides can also
      modulate the angiogenic response of microvessels stimulated by angiogenic
      factors. The experiments reported here make a contribution to the assessment of
      the nature of this angiogenic modulation, by demonstrating that a) GM3
      gangliosides can block the proliferation of endothelium induced by neoplastic
      cells from human tumors of five different origins; b) this block also occurs when
      the endothelial cells are preincubated with GM3 and disappears when the cells are
      returned to a medium poor in GM3; c) in the presence of GM3 the capacity of the
      endothelial cells to bind to fibronectin and to collagen types I and IV was
      sharply reduced; d) concentrations of GM3 able to block endothelial cell growth
      are counteracted by addition to the medium of GT1b ganglioside. The data suggest
      that the prevalence of a microenvironment rich in GM3 prevents proliferation of
      vascular endothelium, but the appropriate presence of another ganglioside, such
      as GT1b, nullifies the effect. Modulation of the angiogenic response of vascular
      endothelium to angiogenic factors released by tumors is probably dependent on the
      distribution and activity of growth factor receptors on the endothelial cell
      surface. The nature and concentration of the gangliosides in the endothelial
      microenvironment have a decisive influence on this event and possibly on the
      progression of tumor-induced angiogenesis.

PMID- 9247099
TI  - Local control of piriform sinus cancer treated by radiation therapy alone.
AB  - Local control rate by radical radiation therapy was analyzed in 33 patients with
      a piriform sinus cancer. Twenty-five patients (76%) were in stage T3 + T4. Local
      recurrence-free survival at 3 years was 49% in T1 + T2 and 25% in T3 + T4 (p =
      0.01). In T1 + T2 lesions, a biologically effective dose for an acute reaction
      over 80 Gy and total treatment time less than 70 days appeared to improve local
      control. In T3 + T4 lesions, good radiation response assessed by the regaining of
      laryngeal mobility affected local control favorably. An esophageal involvement
      and destruction of the laryngeal cartilage as well as soft tissue extension
      precluded the possibility of local control by radiation therapy alone. In
      addition to the T-stage, other tumor factors should also be considered for
      predicting local control with radiation therapy.

PMID- 9247100
TI  - Epidermal growth factor and acute radiation damage in CDF1 mice in vivo.
AB  - The aim was to investigate if extent and time course of acute radiation damage to
      epidermis and intestine could be moderated by epidermal growth factor (EGF).
      Twelve-to-sixteen weeks old female CDF1 mice were treated either by single dose
      local irradiation to the right hind leg or total body irradiation (TBI). The
      endpoints were skin score and lethality, respectively. Human recombinant EGF was
      given s.c. or i.p. at a dose of 5-10 microg/day either before or after
      irradiation. Body weight was significantly higher for EGF treated animals
      compared with controls treated with saline. However, EGF did not reduce the
      median skin score following local irradiation and did not increase LD50 (days 1
      6) following TBI. Further studies using more specific assays are necessary to
      determine if radiation damage to less toxic levels can be ameliorated by EGF.

PMID- 9247101
TI  - Altered fractionation of hemithorax irradiation for pleural mesothelioma and
      failure patterns after treatment.
AB  - Malignant pleural mesothelioma is a rare malignancy with a bleak prognosis. The
      role of radiotherapy has not yet been clarified. Our aim was to study the effect
      of altered fractionation on mesothelioma. We have treated 57 patients, 41 males
      and 16 females, with hemithorax irradiation with six different fractionation
      schedules. All the patients have been included in a combined modality program
      consisting of surgery followed by chemotherapy and finally by hemithorax
      irradiation. The radiotherapy schedules used were: I. Conventional fractionation
      of 20 Gy in 10 fractions over 12 days. II. Split-course radiotherapy 55 Gy in 25
      fractions of 2.2 Gy over 7 weeks (a two weeks rest halfways) followed by a boost
      dose of 15 Gy over 8 days to the major tumour area. III. Hyperfractionation of 70
      Gy over 7 weeks, 1.25 Gy BID with a 6-h interval and a 10-day rest halfways. IV.
      Combined hyperfractionation and hypofractionation, 35 Gy hyperfractionation in 28
      fractions (1.25 Gy BID with a 6-h interval) over three weeks followed by 36 Gy
      hypofractionation 9 fractions of 4 Gy given every other day over 3 weeks to the
      major tumour areas only. V. Hypofractionation of 38.5 Gy over 15 days (9 x 3.5
      Gy). VI. Combined conventional radiotherapy and hypofractionation with 20 Gy
      given conventionally in 10 fractions followed by 10 fractions of 3 Gy over two
      weeks, overall time 4 weeks. The 2-year survival rate of all patients was 21% and
      the 5-year survival rate 9%. Two patients are still alive more than 6 and 9 years
      after radiotherapy. Progression occurred after surgery in four patients, during
      and after chemotherapy in 22 patients and after completed radiotherapy in 29
      patients. The pattern of progression was similar in each treatment group.

PMID- 9247102
TI  - Expression of c-Myc, TGF-alpha and EGF-receptor in sporadic medullary thyroid
      carcinoma.
AB  - In 20 patients with sporadic medullary thyroid carcinoma (MTC), immuno
      histochemistry was used to localize the expression of the c-Myc oncoprotein,
      transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor
      (EGFR) and these three markers were analysed regarding their relation to
      histopathological and histochemical variables of the tumours. The detection rates
      of c-Myc, TGF-alpha and EGFR were 90%, 90% and 95% respectively. Concomitant
      demonstration of the markers was reflected in significant associations
      (correlation factor between TGF-alpha and EGFR was 0.93, p < 0.001). The markers
      were almost invariably located within the cytoplasm, which might suggest their
      crucial role in growth regulation and cell differentiation; this seems especially
      true of TGF-alpha and EGFR. The different markers showed no relation to either
      histopathological or histochemical variables (tumour behaviour, tumour size,
      tumour cell type). The prominent co-expression of c-Myc, TGF-alpha and EGFR
      proteins indicates that in MTC these factors might be of importance for tumour
      cell proliferation via autocrine growth stimulation.

PMID- 9247104
TI  - A possible correlation between growth-factor sensitivity and response to
      mitoxantrone treatment in a murine myeloid leukaemia (SA7HD) cell line.
AB  - SA7 murine myeloid leukaemia cells usually respond to stimulation in vitro by
      WEHI-conditioned medium by displaying increased dose-dependent proliferation.
      However, at recurrence following in vivo treatment of the leukaemia with
      mitoxantrone, the leukaemia cells developed significant insensitivity (p = 0.04)
      to stimulation by WEHI-conditioned medium. This altered growth-factor sensitivity
      was detected when two different assays were used. The recurrent leukaemic cells
      were morphologically indistinguishable from untreated leukaemic cells, but in
      normal mice they regained sensitivity to growth factors after a single
      transplant. The recurrent leukaemic cells were significantly resistant to some
      concentrations of mitoxantrone in vitro (p = 0.012). The magnitude of this
      resistance was mainly a function of the dose of mitoxantrone used in the initial
      treatment of the leukaemia. These data suggest an association between growth
      factor sensitivity and response to mitoxantrone treatment including the
      development of resistance in the SA7HD murine myeloid leukaemia cell line.

PMID- 9247105
TI  - Pericardial tamponade as the first manifestation of adenocarcinoma.
AB  - We hereby report on 13 cases of pericardial tamponade as the first manifestation
      of an adenocarcinoma. The primary tumor was detected in 10 cases: 7 lung, 1
      stomach, 1 breast and 1 thyroid. A first cytologic examination of the pericardial
      fluid yielded the diagnosis of adenocarcinoma in 10 cases, whereas a second
      cytology was needed in another two cases. The pericardial biopsy was positive in
      7 out of 7 patients. The therapeutic procedures included pericardiocentesis in 9
      patients (6 of whom had recurrent tamponade), a pericardial window in 4 and
      pericardiotomy in 4 (without recurrences). The mean survival was 4 months.

PMID- 9247103
TI  - Prognostic factors and treatment outcome in non-Hodgkin's lymphoma of Waldeyer's
      ring.
AB  - Prognostic factors and treatment outcome of 71 patients with non-Hodgkin's
      lymphoma of Waldeyer's ring were analyzed retrospectively. In univariate
      analyses, unfavorable prognosis was associated with primary disease in the base
      of the tongue, stage III-IV diseases, B-symptoms, high-grade histology, T-cell
      phenotype, elevated serum LDH levels, decreased peripheral blood lymphocyte
      counts, and negative response on delayed type hypersensitivity skin reactions.
      Multivariate analysis showed that stage III-IV and T-cell phenotype were
      significant independent risk factors for death. In stage I-II lymphomas, patients
      with unilateral large or bilateral cervical lymph node involvement had a poorer
      prognosis. In stage I-II lymphomas with intermediate or high-grade histology,
      patients who had received radiotherapy with MTCOP-P chemotherapy (pirarubicin,
      cyclophosphamide, vincristine, methotrexate with leucovorin rescue, peplomycin,
      and predonisolone) showed significantly better 5-year disease-free survival rate
      compared with patients treated with radiotherapy alone.

PMID- 9247106
TI  - Tissue polypeptide-specific antigen (TPS) as tumour marker in epithelial ovarian
      cancer.

PMID- 9247107
TI  - Hyalinizing trabecular adenoma of thyroid masquerading as thyroid carcinoma.

PMID- 9247109
TI  - Third space sequestration increases toxicity of fludarabine--a case report.

PMID- 9247108
TI  - Fibrosarcoma in children--a rare tumour with long-term survival even with
      advanced disease--a report of 3 cases.
AB  - Fibrosarcoma is a rare tumour in children. The potential of malignancy has been
      questioned. We present three cases of fibrosarcoma in children . The follow-up
      periods range from 10 to 37 years. The first patient had pulmonary metastases at
      the time of diagnosis in 1958. The primary tumour in fossa ischio-rectalis was
      resected in 1960. Lung metastases were resected in 1960 and 1989. Radiotherapy
      was given in 1992. He is still alive with metastases 37 years after the first
      manifestation of disease. The second patient had a primary tumour and several
      local recurrences in the mandible. He is alive without evidence of disease 4
      years after resection of pulmonary metastases and 21 years after resection of the
      primary tumour. The third patient has no signs of recurrence or metastatic spread
      10 years after a wide excision of subcutaneous tumours of the left upper arm. The
      cases demonstrate a special tumour-entity of low-grade malignancy, which show a
      good prognosis and a wide spectrum of biological behaviour.

PMID- 9247110
TI  - One case of Stewart-Treves syndrome successfully treated at two years by
      chemotherapy and radiation therapy in a 73-year-old woman.

PMID- 9247111
TI  - Disseminated tuberculosis treated with amikacin in a patient with acute
      myelocytic leukemia.

PMID- 9247112
TI  - PDK1, one of the missing links in insulin signal transduction?
AB  - The initial steps in insulin signal transduction occur at the plasma membrane and
      lead to the activation of phosphatidylinositide (PtdIns) 3-kinase and the
      formation of PtdIns(3,4,5,)P3 in the inner leaflet of the plasma membrane which
      is then converted to PtdIns(3,4)P2 by a specific phosphatase. Inhibitors of
      PtdIns 3-kinase suppress nearly all the metabolic actions of insulin indicating
      that PtdIns(3,4,5)P3 and/or PtdIns(3,4)P2 are key 'second messengers' for this
      hormone. A major effect of insulin is its ability to stimulate the synthesis of
      glycogen in skeletal muscle. By 'working backwards' from glycogen synthesis, we
      have dissected an insulin-stimulated protein kinase cascade which is triggered by
      the activation of PtdIns 3-kinase. The first enzyme in this cascade is termed 3
      phosphoinositide-dependent protein kinase (PDK1), because it is only active in
      the presence of PtdIns(3,4,5)P3 or PtdIns(3,4)P2. PDK1 then activates protein
      kinase B (PKB) which, in turn, inactivates glycogen synthase kinase-3 (GSK3),
      leading to the dephosphorylation and activation of glycogen synthase and hence to
      an acceleration of glycogen synthesis. We review the evidence which indicates
      that the phosphorylation of other proteins by PKB and GSK3 is likely to mediate
      many of the intracellular actions of insulin.

PMID- 9247113
TI  - Communication between the extracellular environment, cytoplasmic signalling
      cascades and the nuclear cell-cycle machinery.
AB  - In the past decade, we have gained considerable insight into the identities of
      various cytoplasmic signal transduction cascades and the manner in which they
      operate in response to changes in the extracellular environment. Moreover, we
      have begun to understand what the key players are in cell-cycle regulation and
      how they, in turn, function to promote cell division. A long-standing question,
      however, has been how communication between signalling routes and the cell-cycle
      machinery occurs. This review highlights some recent observations that provide
      possible links between signal transduction and the cell-cycle machinery.

PMID- 9247114
TI  - Simultaneous induction of stimulatory and inhibitory signals by PDGF.
AB  - Platelet-derived growth factor (PDGF) exerts its effects on cells via binding to
      structurally similar alpha- and beta-tyrosine kinase receptors. Ligand binding
      induces receptor dimerization and autophosphorylation which allows docking of SH2
      domain containing signal transduction molecules. At least 10 different SH2 domain
      molecules bind in a specific manner to 11 identified autophosphorylated tyrosine
      residues in the PDGF beta-receptor, thereby initiating signaling pathways leading
      to cell growth and motility. Available information indicates that there is
      considerable cross-talk between different signaling pathways, and that
      stimulatory and inhibitory signals often are initiated in parallel.

PMID- 9247115
TI  - Cyclic AMP signalling and cellular proliferation: regulation of CREB and CREM.
AB  - In eukaryotes, transcriptional regulation upon stimulation of the adenylyl
      cyclase signalling pathway is mediated by a family of cAMP-responsive nuclear
      factors. This family consists of a large number of members which may act as
      activators or repressors. These factors contain the basic domain/leucine zipper
      motifs and bind as dimers to cAMP-response elements (CRE). The function of CRE
      binding proteins (CREB) is modulated by phosphorylation by the cAMP-dependent
      protein kinase. The ICER (inducible cAMP early repressor) protein is the only
      inducible member of this family and is a product of the CREM gene. The induction
      of this powerful repressor is likely to be important for the transient nature of
      cAMP-induced gene expression. CREB proteins have been found to play an important
      role in the physiology of neuroendocrine functions. In addition, recent results
      indicate that CREB and CREM could be involved in the proliferation of hepatocytes
      which follows partial hepatectomy.

PMID- 9247116
TI  - cGMP as second messenger during Dictyostelium chemotaxis.
AB  - The chemoattractant cAMP induces directed cell locomotion in Dictyostelium cells.
      Several second messenger pathways are activated upon binding of cAMP to G-protein
      coupled receptors, including adenylyl cyclase, guanylyl cyclase, phospholipase C,
      and the opening of plasma membrane Ca2+ channels. These second messenger
      responses are unaltered in many chemotactic mutants, except for the cGMP
      response. Activation of guanylyl cyclase depends on G-proteins and is regulated
      by a cGMP-binding protein in a complex manner. This cGMP-binding protein also
      mediates intracellular functions of cGMP to activate a PKC-related kinase that
      phosphorylates myosin II heavy chain, thereby allowing myosin filaments to
      rearrange during cell movement.

PMID- 9247117
TI  - New insights on the functions of the guanylyl cyclase receptors.
AB  - The discovery of at least 29 genes encoding putative guanylyl cyclases in
      Caenorhabditis elegans has raised the question as to whether there are numerous
      receptors yet to be discovered in the mammal. The nematode, however, not only
      seems ideal to study guanylyl cyclase receptor localization and function, given
      the large variety of isoforms, but also leads to possible identification of
      ligands for orphan guanylyl cyclases by the use of genetic and behavioral assays.
      A recent powerful approach to describe the function of different guanylyl cyclase
      isoforms in mammals has been the disruption of the corresponding genes in the
      mouse. A salt resistant elevation of blood pressure, which corresponds to the
      phenotype of 50% of all human patients with essential hypertension, is observed
      in mice lacking the GC-A-receptor. Mice missing the GC-C receptor have been shown
      to be resistant to STa, an E. coli heat-stable enterotoxin, which is largely
      responsible for travellers diarrhea in adults and mortality due to diarrhea in
      infants.

PMID- 9247118
TI  - Molecular diversity of sphingolipid signalling.
AB  - Sphingolipid breakdown products are now being recognized to play a dual role in
      cellular signalling, acting as intracellular as well as extracellular signalling
      molecules. Both types of action may even be found with one sphingolipid species.
      The recent demonstration of G protein-coupled receptors with high affinity for
      sphingosine 1-phosphate and sphingosylphosphorylcholine has been followed by the
      discovery of several novel sphingolipid actions, such as regulation of heart
      rate, oxidative burst, neurite retraction or platelet activation. Ligand profiles
      and concentration-response relationships suggest the existence of putative
      sphingolipid receptor subtypes. Against this background, several observations on
      supposed sphingolipid second messenger actions deserve a new evaluation.

PMID- 9247119
TI  - Biochemistry and genetics of inositol phosphate metabolism in Dictyostelium.
AB  - Biochemical and genetic data on the metabolism of inositol phosphates in the
      microorganism Dictyostelium are combined in a scheme composed of in five
      subroutes. The first subroute is the inositol cycle as found in other organisms:
      inositol is incorporated into phospholipids that are hydrolysed by PLC producing
      Ins(1,4,5)P3 which is dephosphorylated to inositol. The second subroute is the
      sequential phosphorylation of inositol to InsP6; the Ins(3,4,6)P3 intermediate
      does not release Ca2+. The third subroute is the sequential phosphorylation of
      Ins(1,4,5)P3 to InsP6 in a nucleus associated fraction, whereas the fourth
      subroute is the dephosphorylation of Ins(1,3,4,5,6)P5 to Ins(1,4,5)P3 at the
      plasma membrane. This last route mediates Ins(1,4,5)P3 formation in cells with a
      disruption of the single PLC gene. Finally, we recognize the formation of InsP7
      and InsP8 as the fifth subroute.

PMID- 9247120
TI  - Phosphatidylinositol transfer proteins: requirements in phospholipase C signaling
      and in regulated exocytosis.
AB  - Phosphatidylinositol transfer proteins (PITP) are abundant cytosolic proteins
      originally identified because of their ability to act in vitro as specific
      transporters of phosphatidylinositol or phosphatidylcholine between membranes.
      However, the cellular function of mammalian PITP has remained enigmatic till
      recently. Due to the development of reconstitution assays in cytosol-depleted
      cells, PITP was found to be an essential component for phospholipase C-mediated
      hydrolysis of PIP2 and for regulated exocytosis. The exact mechanism how PITP
      exerts its effects is not known but the PI binding/transfer activity of PITP can
      partly explain its cellular function. PITP would enable the local synthesis of
      PIP2 by delivering PI to specialized signaling sites.

PMID- 9247121
TI  - Structure, function and regulation of Ca2+-sensitive cytosolic phospholipase A2
      (cPLA2).
AB  - The 85-kDa cytosolic PLA2 (cPLA2) is present in many cells and tissues and its
      unusual functional properties and catalytic mechanism are being elucidated.
      Notably, cPLA2 becomes catalytically active in the presence of free Ca2+
      concentrations as present in stimulated cells and preferentially cleaves
      arachidonic acid-containing phospholipids. A variety of agonists, growth factors
      and cytokines, as well as stressful stimuli activate cPLA2 to hydrolyze cellular
      phospholipids thereby liberating fatty acids and lysophospholipids and providing
      the precursor substrates for the biosynthesis of eicosanoids and platelet
      activating factor. These products of cPLA2 contribute to inflammatory and
      degenerative disease states and cPLA2 is therefore an attractive target for the
      development of novel therapies.

PMID- 9247122
TI  - Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis.
AB  - From very recent studies, including molecular cloning of cDNA coding for membrane
      receptors, lysophosphatidic acid (LPA) reached the status of a novel phospholipid
      mediator with various biological activities. Another strong argument supporting
      this view was the discovery that LPA is secreted from activated platelets,
      resulting in its appearance in serum upon blood coagulation. The metabolic
      pathways as well as the enzymes responsible for LPA production are poorly
      characterized. However, a survey of literature data indicates some interesting
      issues which might be used as the basis for further molecular characterization of
      phospholipases A able to degrade phosphatidic acid.

PMID- 9247124
TI  - The interaction of Ras with GTPase-activating proteins.
AB  - Ras plays a major role as a molecular switch in many signal transduction pathways
      which lead to cell growth and differentiation. The GTPase reaction of Ras is of
      central importance in the function of the switch since it terminates Ras-effector
      interactions. GTPase-activating proteins (GAPs) accelerate the very slow
      intrinsic hydrolysis reaction of the GTP-bound Ras by several orders of magnitude
      and thereby act as presumably negative regulators of Ras action. The GTP
      hydrolysis of oncogenic mutants of Ras remains unaltered. In this review we
      discuss recent biochemical and structural findings relating to the mechanism of
      GAP action, which strengthen the hypothesis that GAP accelerates the actual
      cleavage step by stabilizing the transition state of the phosphoryl transfer
      reaction.

PMID- 9247123
TI  - In search of a function for the Ras-like GTPase Rap1.
AB  - Rap1 (Krev-1) is a small GTPase first identified as a transformation suppressor
      of K-ras. This GTPase is very similar to Ras, particularly in the effector
      region, but its function is still elusive. Recent progress in the search for Rap1
      function has come from the development of a novel assay to measure Rap1
      activation. Using this assay activation of Rap1 was observed in human platelets
      and neutrophils after stimulation with various agonists. We speculate that Rap1
      plays a role in one of the specialised functions of these cells.

PMID- 9247125
TI  - Rho effectors and reorganization of actin cytoskeleton.
AB  - The small GTPase Rho regulates several actomyosin-based cellular processes such
      as cell adhesion, cytokinesis and contraction. The biochemical mechanisms of
      these actions remain unknown. Recently, several GTP-Rho binding proteins were
      isolated. Among them, p140mDia and p160ROCK appear to work as Rho effectors
      mediating its action on the cytoskeleton. p140mDia induces actin polymerization
      by recruiting an actin binding protein, profilin, to the site of Rho action.
      p160ROCK induces focal adhesions and stress fibers by activating integrin and
      clustering them by the use of myosin-based contractility.

PMID- 9247126
TI  - Regulation of proliferation and apoptosis by Ras and Rho GTPases through specific
      phospholipid-dependent signaling.
AB  - Small GTPases are molecular switches that control signaling pathways critical for
      diverse cellular functions. Recent evidence indicates that multiple effector
      molecules can be activated by small GTPases. As a result, complex biological
      processes such as cell proliferation and apoptosis are turned on. Thus, rather
      than a single linear pathway from the membrane to the nucleus, the integration of
      complementary signals is required for these events to occur. In fact, the
      coordinated activation of small GTPases may constitute some of the critical
      modulators of those signals triggering either proliferation or cell death. In
      addition to the activation of specific kinases cascades, phospholipid-derived
      messengers are candidates to compose some of the most critical elements
      associated to regulation of signaling cascades capable of discerning among life
      and death. Both proliferation and apoptosis needs competence and progression
      signals. Phospholipase D and sphingomyelinase may be important players in this
      decision-maker step.

PMID- 9247127
TI  - The modular phosphorylation and activation of p70s6k.
AB  - The activation of p70s6k is accompanied by a complex series of phosphorylation
      events. In this review we propose a model of activation which divides p70s6k into
      four functional modules that cooperate in leading to full enzyme activity. In the
      light of the model, we suggest how candidate effectors of p70s6k activation might
      function by directing the phosphorylation of specific sites.

PMID- 9247128
TI  - The ErbB signaling network in embryogenesis and oncogenesis: signal
      diversification through combinatorial ligand-receptor interactions.
AB  - Ligand-induced activation of receptor tyrosine kinases (RTK) results in the
      initiation of diverse cellular pathways, including proliferation, differentiation
      and cell migration. The ErbB family of RTKs represents a model for signal
      diversification through the formation of homo- and heterodimeric receptor
      complexes. Each dimeric receptor complex will initiate a distinct signaling
      pathway by recruiting a different set of Src homology 2- (SH2-) containing
      effector proteins. Further complexity is added due to the existence of an
      oncogenic receptor that enhances and stabilizes dimerization but has no ligand
      (ErbB-2), and a receptor that can recruit novel SH-2-containing proteins, but is
      itself devoid of kinase activity (ErbB-3). The resulting signaling network has
      important implications for embryonic development and malignant transformation.

PMID- 9247129
TI  - The novel estrogen receptor-beta subtype: potential role in the cell- and
      promoter-specific actions of estrogens and anti-estrogens.
AB  - The recent discovery that an additional estrogen receptor (ER) subtype is present
      in various rat, mouse and human tissues has advanced our understanding of the
      mechanisms underlying estrogen signalling. The discovery of a second ER subtype
      (ERbeta) suggests the existence of two previously unrecognised pathways of
      estrogen signalling: via the ERbeta subtype in tissues exclusively expressing
      this subtype and via the formation of heterodimers in tissues expressing both ER
      subtypes. Various models have been suggested as explanations for the striking
      cell- and promoter-specific effects of estrogens and anti-estrogens, all on the
      basis of the assumption that only a single ER gene exists. This minireview
      describes several of these models and focuses on the potential role which the
      novel ERbeta subtype might have in this regard.

PMID- 9247130
TI  - Using structure to define the function of phosphoinositide 3-kinase family
      members.

PMID- 9247131
TI  - Cell death induction by receptors of the TNF family: towards a molecular
      understanding.

PMID- 9247132
TI  - Molecular cloning and characterization of the human p27Kip1 gene promoter.
AB  - p27Kip1 is an inhibitor of multiple cyclin-dependent kinases (cdk), and can
      arrest the cell-cycle progression by inhibiting the phosphorylation of the
      retinoblastoma gene family products. Tumor formation in p27Kip1 knockout mice
      clearly shows that p27Kip1 plays an important role in inhibiting tumor formation
      and progression. To investigate the mechanism of transcriptional p27Kip1 gene
      expression, we isolated the genomic DNA fragment of the 5' flanking region of the
      human p27Kip1 gene and characterized its promoter region. The human p27Kip1
      promoter is TATA-less, and the sequence is highly homologous to the murine
      p27Kip1 promoter sequence. In the promoter assay, deletion from -774 to -435
      relative to the initiating codon resulted in a 15-20-fold reduction of the
      p27Kip1 promoter activity, suggesting that the elements for basal promoter
      activity exist in this highly conserved 340 bp region, where putative CTF and ATF
      sites are conserved.

PMID- 9247133
TI  - The uptake of cholesterol at the small-intestinal brush border membrane is
      inhibited by apolipoproteins.
AB  - The uptake of free and esterified cholesterol at the brush border membrane is
      protein-mediated. Here we show that this sterol uptake is effectively inhibited
      by exchangeable serum apolipoproteins. Binding of the apolipoprotein to the brush
      border membrane mediates the inhibitory effect. Evidence is presented to show
      that the structural motif responsible for the inhibition is the amphipathic alpha
      helix.

PMID- 9247134
TI  - Arrestins expressed in killifish photoreceptor cells.
AB  - Two kinds of cDNA fragments (KfhArr-R and KfhArr-C) encoding the putative
      arrestins of killifish, Oryzias latipes, were isolated. The distributions of
      these transcripts were investigated by in situ hybridization, and it was
      demonstrated that KfhArr-R and KfhArr-C are expressed in, respectively, rod and
      all four types of cone cells. The deduced amino acid sequences of KfhArr-R and
      KfhArr-C are closely related to human S-antigen (rod arrestin) and X-arrestin
      (cone arrestin), respectively. Phylogenetic analysis of arrestin sequences
      suggests that vertebrate visual arrestins form a single cluster distinct from
      other arrestins and diverged to form rod and cone subtypes before the divergence
      between teleosts and tetrapods. It is speculated that the divergence pattern of
      vertebrate visual arrestins may prove to be reflected in the divergence of the
      proteins participating in the respective phototransduction cascades.

PMID- 9247135
TI  - The NMR solution structure of the NMDA receptor antagonist, conantokin-T, in the
      absence of divalent metal ions.
AB  - The solution conformation of conantokin-T, a Gla-containing 21-residue peptide,
      (G1 EgammagammaY5QKMLgamma10NLRgammaA15EVKKN20A-amide), in the absence of
      divalent metal ions, was studied by use of two-dimensional proton NMR
      spectroscopy. The peptide is helical from the N-terminus to the C-terminus, as
      defined by upfield-shifted alpha-proton resonances and by characteristic NOE
      connectivities. Extensive interactions among the amino acid side-chains were
      identified from the NOESY spectra of this peptide in a buffered aqueous solution.
      Four hydrophobic residues Tyr5, Met8, Leu9, and Leu12 contact one another in a
      stable cluster, even in the presence of 6 M urea. The solution structure of
      conantokin-T is a well-defined alpha-helix, having RMSD values for the backbone
      and all heavy atoms of 0.40 A and 0.77 A, respectively. Potential repulsion
      between the negatively-charged side chains of Gla10 and Gla14 is minimized by a
      Gln6-Gla10 hydrogen bond and by an Arg13-Gla14 ion-pair interaction. The C
      terminal amide and the Asn20 side-chain amide both interact with the backbone and
      minimize fraying at the C-terminal end of the alpha-helix. This study provides a
      basis to evaluate the changes in peptide conformation concomitant upon the
      binding of divalent metal ions. In addition, this investigation demonstrates that
      apo-conantokin-T has almost all of the favorable interactions that are known to
      contribute to helical stabilization in proteins and monomeric helices.

PMID- 9247136
TI  - Phage display of Bacillus thuringiensis CryIA(a) insecticidal toxin.
AB  - The display of proteins or peptides on the surface of filamentous phages or
      phagemids has been shown to be a very powerful technology for the rescue of
      specific binders from large combinatorial libraries, as well as to select
      derivatives of known proteins with altered binding properties. The Bacillus
      thuringiensis (Bt) crystal proteins are a large family of insecticidal toxins
      which bind to receptors found on the brush border of larval midgut cells,
      different crystal toxins having different larval specificities. Here we describe
      the display of different CryIA(a) toxin regions on the surface of phagemids using
      the display vector pHEN1, the purpose being the identification of toxin sequences
      suitable for mutagenesis and selection using phage display. We show that CryIA(a)
      domain II, in which the receptor binding activity is located, is efficiently
      displayed as well as being secreted as soluble protein into the periplasm of
      bacterial cell. This forms the basis of a simple means for the modification of
      toxin specificity and the selection of toxin proteins with novel or expanded host
      ranges.

PMID- 9247137
TI  - Activation of alpha7 nicotinic acetylcholine receptor promotes survival of spinal
      cord motoneurons.
AB  - Spinal cord motoneurons (MNs) undergo a process of cell death during embryonic
      development and are the target of lethal acquired or inherited disorders, such as
      the amyotrophic lateral sclerosis. Therefore, the identification of mechanisms
      leading to MN survival is of crucial importance. Elevations in intracellular Ca2+
      promote chicken MN survival during the embryonic period of naturally occurring
      cell death. We have recently demonstrated that the alpha7 nicotinic acetylcholine
      receptor (nAChR) mediates significant increases in free Ca2+ concentration at
      membrane potentials at which other pathways for Ca2+ influx are inactive.
      Although it is possible that Ca2+ influx through alpha7 nAChR promotes cell
      survival, the relation between alpha7 nAChR activation, cytosolic free Ca2+ and
      mammalian spinal cord MN survival has not been established. In the present study
      we have now demonstrated that Ca2+ influx through the alpha7-subunit is
      sufficient to rescue a significant number of cultured spinal cord MNs from
      programmed cell death induced by trophic factor deprivation. This is the first
      demonstration that neuronal nAChRs are involved in the regulation of MN survival.

PMID- 9247138
TI  - The nitric oxide synthase of mouse spermatozoa.
AB  - Nitric oxide synthase (NOS) was evidenced in mature mouse spermatozoa by means of
      biochemical techniques and Western blot. During 120 min of incubation, 10(7)
      spermatozoa synthesized 7 +/- 2 pmol of L-[14C]citrulline. Besides, L-citrulline
      formation depended on the incubation time and on the concentration of L-arginine
      present in the incubation medium. Different concentrations of N(G)-nitro-L
      arginine methyl ester (L-NAME) but not aminoguanidine, inhibited L
      [14C]citrulline formation. Western-blot analysis of solubilized sperm proteins
      revealed a unique band of M(r)=140 kDa with the neural, endothelial and inducible
      NOS antisera tested. These results provide evidence that mature mouse sperm
      contains a NOS isoform and that spermatozoa have the potential ability to
      synthesize NO, suggesting a role for endogenous NO on mammalian sperm function.

PMID- 9247139
TI  - GroEL provides a folding pathway with lower apparent activation energy compared
      to spontaneous refolding of human carbonic anhydrase II.
AB  - The kinetics of the refolding of the enzyme, human carbonic anhydrase II (HCA
      II), at different temperatures, together with the Escherichia coli chaperonin
      GroEL, has been studied. The Arrhenius plots for the spontaneous, GroEL-assisted,
      and GroEL/ES-assisted refolding of HCA II show that the apparent activation
      energy (E(a)) is lower in the presence of the chaperonin GroEL alone than for the
      spontaneous reaction, whereas the apparent activation energy for the GroEL/ES
      assisted reaction is almost the same as for the spontaneous reaction (85, 46, and
      72 kJ/mol, for the spontaneous, GroEL, and GroEL/ES-assisted reactions,
      respectively).

PMID- 9247140
TI  - High expression of the yeast syntaxin-related Vam3 protein suppresses the protein
      transport defects of a pep12 null mutant.
AB  - The Pep12 protein of Saccharomyces cerevisiae is a member of the syntaxin family
      thought to function as target membrane receptor (t-SNARE) for vesicular
      intermediates travelling between the Golgi apparatus and the vacuole. Exploiting
      the temperature-sensitive growth phenotype of pep12 deletion strains, we
      identified VAM3 as a multicopy suppressor. Vam3p is another syntaxin-related
      protein which on high expression restored vacuole acidification of pep12 null
      mutants and effectively suppressed their sorting and maturation defects of
      vacuolar hydrolases. We conclude that Vam3p acts either as a bypass suppressor or
      by functionally replacing Pep12p at an endosomal, prevacuolar compartment.

PMID- 9247141
TI  - A mutant form of the ribosomal protein L1 reveals conformational flexibility.
AB  - The crystal structure of the mutant S179C of the ribosomal protein L1 from
      Thermus thermophilus has been determined at 1.9 A resolution. The mutant molecule
      displays a small but significant opening of the cavity between the two domains.
      The domain movement seems to be facilitated by the flexibility of at least two
      conserved glycines. These glycines may be necessary for the larger conformational
      change needed for an induced fit mechanism upon binding RNA. The domain movement
      makes a disulfide bridge possible between the incorporated cysteines in two
      monomers of the mutant L1.

PMID- 9247142
TI  - Interaction of bacteriophage T4 AsiA protein with Escherichia coli sigma70 and
      its variant.
AB  - Bacteriophage T4 produces a small protein AsiA, which inhibits transcription from
      sigma70-dependent promoters in E. coli by tightly binding to sigma70 and is
      therefore termed as anti-sigma factor. We observed that there was no inhibition
      of single round transcription at lac UV5 promoter when AsiA was added to
      preformed open complex between RNA polymerase and template DNA. However,
      transcription was found to proceed normally at 'extended -10' promoters in the
      presence of AsiA. It appears therefore that AsiA binds sigma70 at its 4.2
      subdomain or in its close vicinity. Further experiments on immunoprecipitation of
      sigma70 and a mutant sigma70-V576G with AsiA seem to corroborate such conclusion.

PMID- 9247143
TI  - Bcl-2 protein inhibits oxysterol-induced apoptosis through suppressing CPP32
      mediated pathway.
AB  - Oxysterols are presumed to mediate cytotoxicity of oxidized LDL in
      atherosclerotic lesions. To elucidate its molecular mechanism, we established
      murine macrophage-like P388-D1 cells which over-express Bcl-2 protein by
      retrovirus-mediated gene transfer. Oxysterols (7-ketocholesterol, 25
      hydroxycholesterol) induced nuclear condensation and oligonucleosomal DNA
      fragmentation, which were partially inhibited by Bcl-2 over-expression. Though
      CPP32 inhibitor suppressed the cell death in control cells, it showed no additive
      protection in the cells over-expressing Bcl-2. These findings indicate that
      oxysterols induce apoptosis via Bcl-2-inhibitable and -uninhibitable pathways,
      and the former depends on CPP32 activation.

PMID- 9247144
TI  - Effect of anti-apoptotic genes and peptide inhibitors on cytoplasmic
      acidification during apoptosis.
AB  - Cytoplasmic acidification has been shown to occur during the apoptotic process of
      cell death although its relation with other events in the process are not yet
      clear. AK-5 tumor cells have been shown to undergo apoptosis upon treatment with
      stimuli like dexamethasone (1 microM) or with serum from animals that reject AK-5
      tumor. The current study was designed to measure the extent of cytoplasmic
      acidification during apoptosis in AK-5 cells and to study the effect of
      antiapopoptic genes and peptide inhibitors on cytoplasmic acidification. Our
      results show that AK-5 cells when triggered into apoptosis show intracellular
      acidification by about 0.2 pH units and this is prevented when cells are treated
      with peptide inhibitors. In addition cytoplasmic acidification does not occur
      when AK-5 cells are transfected with anti-apoptotic genes Nedd-2 A.S, Crm A or
      bcl-2 which inhibit apoptosis.

PMID- 9247145
TI  - The effect of some peptides from the hibernating brain on Ca2+ current in cardiac
      cells and on the activity of septal neurons.
AB  - The effects of the peptides TSKYR and DY isolated from the brain of hibernating
      ground squirrels on Ca2+ current were studied. TSKYR activated Ca2+ current in
      frog auricle fibers and in single cells from frog ventricle whereas DY blocked
      Ca2+ current in both preparations. In isolated rat and ground squirrel
      cardiocytes, TSKYR had no effect on Ca2+ current, and DY increased it. In brain
      slices of rat, DY blocked the activity of medial septal neurons. TSKYR increased
      activity of septal neurons at the initial phase, which was followed by decrease
      of neuronal activity.

PMID- 9247146
TI  - JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to
      assess delta psi changes in intact cells: implications for studies on
      mitochondrial functionality during apoptosis.
AB  - The sensitivity and specificity of three fluorescent probes used for
      cytofluorimetric analysis of mitochondrial membrane potential (delta psi) were
      studied in the U937 human cell line. First, the role of plasmamembrane in
      influencing the binding of the probes to mitochondria has been investigated. The
      depolarization of plasmamembrane with high doses of extracellular KCl had no
      immediate effects on the loading of JC-1, DiOC6(3) and rhodamine 123 (R123).
      However, after a few hours of culture in the presence of KCl, significant changes
      were observed only in cells stained with DiOC6(3). Second, a comparative study
      was performed concerning the effects of agents capable of collapsing deltapsi.
      While adding FCCP to cell cultures resulted in consistent changes in the
      fluorescence emission of both JC-1 and DiOC6(3) - but not of R123 - only cells
      stained with JC-1 responded to valinomycin. On the whole, our data indicate that
      JC-1 is a reliable probe for analyzing delta psi changes with flow cytometry,
      while the others show a lower sensitivity (R123), or a non-coherent behaviour,
      due to a high sensitivity to changes in plasmamembrane potential [DiOC6(3)].
      These data cast some doubts on those studies that, using fluorescent probes that
      have a low sensitivity to delta psi, hypothesized that the fall in delta psi is
      one of the early events, if not one of the main causes, of apoptosis.

PMID- 9247147
TI  - beta-Adrenergic stimulation of interleukin-1alpha and interleukin-6 expression in
      mouse brown adipocytes.
AB  - Mouse brown adipocytes in primary culture were shown to contain high levels of
      mRNA for interleukin-1alpha (IL-1alpha) which could be further stimulated up to 9
      fold by norepinephrine (NE). Even higher stimulation by NE, up to 40-fold, was
      found in case of interleukin-6 (IL-6). Time-course of activation of both genes
      was biphasic, but the response of IL-6 gene was slower than of IL-1alpha gene. IL
      1alpha mRNA level reached the maximum after 1 h and the second, lower increase,
      occurred after 8 h. IL-6 mRNA level showed first maximum after 2 h, but the
      highest level was found after 8 h. Similarly to NE, the expression of IL-1alpha
      and IL-6 genes was stimulated by selective beta-adrenergic agonist isoproterenol,
      beta3-selective agonist CGP-12117, forskoline and db-cAMP. The activation of both
      genes by CGP-12177 was dose-dependent with the optimum at 100 nM concentration.
      Stimulation of alpha-adrenergic receptors by cirazoline and oxymetazoline was
      without any effect. When the expression of IL-6 was studied at the protein level,
      the stimulation of IL-6 gene via beta3-receptors resulted in secretion of IL-6 up
      to the concentration 10 ng/ml culture media in 24 h. The results indicate a new
      type of regulation of expression of IL-1alpha and IL-6 genes in brown adipocytes
      by catecholamines acting via beta3-adrenergic receptors. The resulting increase
      in IL-6 production by brown adipocytes could significantly contribute to systemic
      levels of IL-6.

PMID- 9247148
TI  - Apoptosis induced by HIV-gp120 in a Th1 clone involves the generation of reactive
      oxygen intermediates downstream CD95 triggering.
AB  - HIV-gp120 sensitizes Th1 clones from seronegative donors to apoptosis, which
      occurs through two distinct events: expression of CD95L followed by its
      interaction with CD95 to trigger cell death. gp120-apoptosis of the Th1 clone 103
      was inhibited by Cyclosporin A, the PTK inhibitors Genistein and PNU152518, as
      well as the anti-oxidants Ascorbic Acid and Glutathione. Cyclosporin A interfered
      with CD95L expression, Ascorbic Acid and Glutathione inhibited cell death
      triggered by CD95/CD95L interaction; Genistein and PNU152518 acted on both steps.
      The occurrence of oxidative stress during CD95-dependent apoptosis was supported
      by the direct evidence of ROI production.

PMID- 9247149
TI  - Ceruloplasmin, transferrin and apotransferrin facilitate iron release from human
      liver cells.
AB  - The rate of iron release from HepG2 liver cells was increased not only by
      extracellular apotransferrin, but also by diferric transferrin, in a non
      additive, concentration-dependent manner and to a similar magnitude. This
      suggests that rapid equilibration between receptor-mediated uptake and the
      release process determines net iron retention by the liver. Release was also
      accelerated by ceruloplasmin; most importantly, the effect of this protein was
      greatest when iron release was occurring rapidly, stimulated by apotransferrin,
      or under conditions of limited oxygen. Thus iron release involves both
      apotransferrin and ferrotransferrin, with ceruloplasmin playing a role in tissues
      with limited oxygen supply, as in the liver in vivo.

PMID- 9247150
TI  - A novel fluorescent marker for assembled mitochondria ATP synthase of yeast. OSCP
      subunit fused to green fluorescent protein is assembled into the complex in vivo.
AB  - We have shown that OSCP, a subunit of yeast mitochondrial ATP synthase, can be
      incorporated into the intact enzyme as a fusion protein representing OSCP fused
      at its C-terminus to the green fluorescent protein (GFP) of Aequorea victoria.
      The relevant fusion OSCP-GFP-h6 additionally contains a hexahistidine tag at the
      C-terminus. Expression of OSCP-GFP-h6 in yeast cells lacking endogenous OSCP led
      to the efficient restoration of growth of cells on the non-fermentable substrate,
      ethanol. Confocal laser scanning microscopy revealed fluorescence due to GFP in
      mitochondria of cells expressing OSCP-GFP-h6. Use of immobilised metal ion
      affinity chromatography enabled the recovery of assembled ATP synthase complexes
      which contained OSCP-GFP-h6 identified by its mobility on SDS-PAGE and
      immunoreactivity to anti-OSCP and anti-GFP antibodies. The successful isolation
      of the assembled multisubunit ATP synthase containing GFP fused to one of the
      essential subunits of the complex widely expands the potential applications of
      GFP. In principle, these include the spatial and temporal monitoring of ATP
      synthase complexes in vivo, and the exploration of interactions involving ATP
      synthase subunits by fluorescence resonance energy transfer (FRET).

PMID- 9247151
TI  - 9,13-di-cis-Retinoic acid induces the production of tPA and activation of latent
      TGF-beta via RAR alpha in a human liver stellate cell line, LI90.
AB  - We studied the mechanism by which 9,13-di-cis-retinoic acid (9,13dcRA), a novel
      and endogenous stereoisomer of all-trans-RA, induces TGF-beta formation in a
      human liver stellate cell line, LI90. 9,13dcRA induced the expression of RAR
      alpha and RARbeta, enhanced the production of tissue-type plasminogen activator
      (tPA), thereby, surface plasmin levels, and induced the activation of latent TGF
      beta. Similar effects were obtained with RAR alpha-selective retinoid, but not
      with RARbeta- or RARgamma-selective retinoid, and the induction was inhibited by
      RAR alpha-selective antagonist. These results suggest that 9,13dcRA up-regulates
      tPA expression, resulting in the formation of TGF-beta by LI90 cells, at least in
      part, via induction and activation of RAR alpha.

PMID- 9247152
TI  - HIV-1 gp120 glycoprotein affects the astrocyte control of extracellular glutamate
      by both inhibiting the uptake and stimulating the release of the amino acid.
AB  - The mechanisms of HIV-1 neurotoxicity remain still undefined although the
      induction of signalling events and a modest inhibition of glutamate uptake
      induced by the envelope glycoprotein, gp120, have called attention to astrocytes.
      Here we demonstrate that the levels at which the viral glycoprotein affects
      glutamate homeostasis of astrocyte cultures are at least two: not only the
      inhibition of uptake, due to an effect at site(s) away from the transporters of
      the amino acid but also a slow stimulation of release. The combination of these
      two events accounts for a considerable steady increase of the extracellular
      concentration of the excitatory amino acid which could play an important role in
      the neurotoxicity often observed in AIDS patients.

PMID- 9247153
TI  - Immunological identification of the alternative oxidase of Acanthamoeba
      castellanii mitochondria.
AB  - Mitochondria of the protozoa Acanthamoeba castellanii possess a cyanide
      insensitive oxidase cross-reacting with monoclonal antibodies raised against the
      plant alternative oxidase. Immunoblotting revealed three monomeric forms (38, 35,
      and 32 kDa) and very low amounts of a single 65 kDa dimeric form. Cross-linking
      studies suggest that while in plants the alternative oxidase occurs as a dimer,
      in amoeba it functions as a monomer. Immunologically detectable protein levels
      change with the age of amoeba cell culture. Increased amounts of the 35 kDa
      protein are accompanied by an increase in the activity of cyanide-resistant
      respiration.

PMID- 9247154
TI  - Studies on ion channel antagonist-binding sites in sunflower protoplasts.
AB  - The cytological location of ion channel antagonist-binding sites was studied in
      sunflower protoplasts using the fluorescent probes DM-Bodipy-PAA and DM-Bodipy
      DHP. The binding specificity of the probes was established by competition
      experiments with Bepridil, phenylalkylamine (Verapamil) and dihydropyridine
      (Nifedipine) which are known as calcium and potassium channel antagonists.
      Quantitative image analysis of the fluorescence emitted by the protoplasts showed
      the existence of interactions between PAA- and DHP-binding sites. Moreover,
      studies on the cytolocalization of the PAA receptors by confocal imaging showed
      that in freshly isolated protoplasts, DM-Bodipy-PAA binds exclusively at sites
      located in the cortical region of the cell.

PMID- 9247155
TI  - A Mox homeobox gene in the gastropod mollusc Haliotis rufescens is differentially
      expressed during larval morphogenesis and metamorphosis.
AB  - We have isolated a homeobox-containing cDNA from the gastropod mollusc Haliotis
      rufescens that is most similar to members of the Mox homeobox gene class. The
      derived Haliotis homeodomain sequence is 85% identical to mouse and frog Mox-2
      homeodomains and 88.9% identical to the partial cnidarian cnox5-Hm homeodomain.
      Quantitative reverse transcription-polymerase chain reaction analysis of mRNA
      accumulation reveals that this gene, called HruMox, is expressed in the larva,
      but not in the early embryo. Transcripts are most prevalent during larval
      morphogenesis from trochophore to veliger. There are also transient increases in
      transcript prevalence 1 and 3 days after the intitiation of metamorphosis from
      veliger to juvenile. The identification of a molluscan Mox homeobox gene that is
      more closely related to vertebrate genes than other protostome (e.g. Drosophila)
      genes suggests the Mox class of homeobox genes may consist of several different
      families that have been conserved through evolution.

PMID- 9247157
TI  - The propeptide of subtilisin BPN' as a temporary inhibitor and effect of an amino
      acid replacement on its inhibitory activity.
AB  - The propeptide of subtilisin-family proteases is known to exhibit inhibitory
      activity toward a cognate protease in addition to its function as an
      intramolecular chaperone. For detailed investigation of its inhibitory
      properties, the propeptide of subtilisin BPN' was produced in Escherichia coli.
      Inhibitory activity measurements and electrophoresis showed that the propeptide
      was a temporary inhibitor, which was initially potent but was gradually degraded
      by subtilisin BPN' through specific intermediates. The main cleavage site was
      identified as Glu53-Lys54, with minor sites at Thr17-Met18 and Met21-Ser22, which
      were located in turn regions of the propeptide in the complex with subtilisin
      BPN'. Since the isolated propeptide has been shown not to form a tertiary
      structure, these results indicate that main digestions proceed through
      proteolytic attack of subtilisin toward the accessible sites of the propeptide in
      the complex with subtilisin. Therefore, replacement of Glu53 at the main cleavage
      site by Asp, which is a less favorable amino acid than Glu for subtilisin, makes
      the propeptide a more resistant temporary inhibitor.

PMID- 9247156
TI  - Transfer RNA(Phe) isoacceptors possess non-identical set of identity elements at
      high and low Mg2+ concentration.
AB  - Primary structures of phage T5- and Escherichia coli-encoded tRNA(Phe) are
      distinct at four out of 11 positions known as identity elements for E. coli
      phenylalanyl-tRNA synthetase (FRS). In order to reveal structural requirements
      for FRS recognition, aminoacylation of wild-type phage T5 tRNA(Phe) gene
      transcript and mutants containing substitutions of the identity elements at
      positions 20, 34, 35 and 36 was compared with E. coli tRNA(Phe) gene transcript.
      The wild-type phage T5 transcript can be aminoacylated with the same catalytic
      efficiency as the E. coli counterpart. However, the maximal aminoacylation rate
      for T5 and E. coli transcripts was reached at different Mg2+ concentrations: 4
      and 15 mM, respectively. Aminoacylation assays with tRNA(Phe) mutants revealed
      that (i) phage transcripts with the substituted anticodon bases at positions 35
      and 36 were efficient substrates for aminoacylation at 15 mM Mg2+ but not at
      optimal 4 mM Mg2+; (ii) any change of G34 in phage transcripts dramatically
      decreased the aminoacylation efficiency at both 4 and 15 mM Mg2+ whereas G34A
      mutation in the E. coli transcript exhibits virtually no influence on
      aminoacylation rate at 15 mM Mg2+; (iii) substitution of A20 with U in the phage
      transcript caused no significant change in the aminoacylation rate at both Mg2+
      concentrations; (iv) phage transcripts with double substitutions A20U+A35C and
      A20U+A36C were very poor substrates for FRS. Collectively, the results indicate
      the non-identical mode of tRNA(Phe) recognition by E. coli FRS at low and high
      Mg2+ concentrations. Probably, along with identity elements, the local tRNA
      conformation is essential for recognition by FRS.

PMID- 9247158
TI  - Brefeldin A interferes with peroxisomal protein sorting in the yeast Hansenula
      polymorpha.
AB  - We have studied the effect of brefeldin A (BFA), a fungal toxin that interferes
      with coated vesicle formation, on the biogenesis of peroxisomes in the yeast
      Hansenula polymorpha. Addition of BFA (20 microg/ml) to cultures of H. polymorpha
      partially inhibited the development of peroxisomes and resulted in the reversible
      accumulation of newly synthesized peroxisomal membrane and matrix proteins at the
      endoplasmic reticulum. In contrast, BFA did not interfere with the selective
      degradation of peroxisomes. Taken together, our data suggest that the ER plays a
      crucial role in peroxisome biogenesis in H. polymorpha, possibly in the
      biosynthesis of the peroxisomal membrane.

PMID- 9247159
TI  - Characterisation of neprilysin (EC 3.4.24.11) S2' subsite.
AB  - Neprilysin is a neutral peptidase that cleaves small peptide substrates on the
      amino-side of hydrophobic amino acid residues. In the present study, we have used
      inhibition of non-mutated and mutated enzymes with dipeptide inhibitors and
      hydrolysis of the substrate [Leu5, Arg6]enkephalin in order to evaluate the
      contribution of the S2' subsite to substrate and inhibitor binding. Our results
      suggest that (1) Arg-102 and Asn-542 provide major contributions to the
      interaction of the enzyme with the P2' residue of the substrate, (2) the S2'
      subsite is vast and can accommodate bulky side chains, and (3) Arg-102 restricts
      access to the S2' subsite to some side chains such as arginine.

PMID- 9247160
TI  - Estrogen receptor mRNA in mineralized tissues of rainbow trout: calcium
      mobilization by estrogen.
AB  - RT-PCR was undertaken on total RNA extracts from bone and scales of the rainbow
      trout, Oncorhynchus mykiss. The rainbow trout estrogen receptor (ER)-specific
      primers used amplified a single product of expected size from each tissue which,
      using Southern blotting, strongly hybridized with a 32P-labelled rtER probe under
      stringent conditions. These data provide the first in vivo evidence of ER mRNA in
      bone and scale tissues of rainbow trout and suggest that the effects of estrogen
      observed in this study (increased bone mineral and decreased scale mineral
      contents, respectively) may be mediated directly through ER.

PMID- 9247161
TI  - Photodynamic membrane damage at the level of single ion channels.
AB  - Illumination of cellular membranes by visible light in the presence of
      appropriate photosensitizers is known to inactivate specific ionic pathways and
      to increase the unspecific leak conductance of the membranes. While previous
      studies have concentrated on the macroscopic ionic currents, the present study
      separates the two phenomena at the microscopic level. Using opossum kidney (OK)
      cells as epithelial model system and photofrin II as sensitizer, the patch-clamp
      technique in inside-out configuration has been applied to show the inactivation
      of single ion channels immediately after start of illumination and the subsequent
      strong increase of the leak conductance. Inactivation is shown for two kinds of
      channels: the large-conductance Ca2+-dependent K+ channel (maxi-K(Ca)) and the
      stretch-activated nonselective cation channel (SA-cat).

PMID- 9247162
TI  - Conventional and saturation-transfer EPR of spin-labeled mutant bacteriophage M13
      coat protein in phospholipid bilayers.
AB  - A mutant of bacteriophage M13 was prepared in which a cysteine residue was
      introduced at position 25 of the major coat protein. The mutant coat protein was
      spin-labeled with a nitroxide derivative of maleimide and incorporated at
      different lipid-to-protein (L/P) ratios in DOPC or DOPG. The rotational dynamics
      of the reconstituted mutant coat protein was studied using EPR and saturation
      transfer (ST) EPR techniques. The spectra are indicative for an anisotropic
      motion of the maleimide spin label with a high order parameter (S = 0.94). This
      is interpreted as a wobbling motion of the spin label with a correlation time of
      about 10(-6) to 10(-5) s within a cone, and a rotation of the spin label about
      its long molecular axis with a correlation time of about l0(-7) s. The wobbling
      motion is found to correspond generally to the overall rotational motion of a
      coat protein monomer about the normal to the bilayer. This motion is found to be
      sensitive to the temperature and L/P ratio. The high value of the order parameter
      implies that the spin label experiences a strong squeezing effect by its local
      environment, that reduces the amplitude of the wobbling motion. This squeezing
      effect is suggested to arise from a turn structure in the coat protein from Gly23
      to Glu20.

PMID- 9247163
TI  - Dynamic properties of Newcastle Disease Virus envelope and their relations with
      viral hemagglutinin-neuraminidase membrane glycoprotein.
AB  - The lipid composition of Newcastle Disease Virus (NDV) Clone-30 strain shows a
      low lipid/protein ratio, a high cholesterol/phospholipid molar ratio, and major
      phospholipids being qualitatively different to other NDV strains. The major fatty
      acyl constituents are palmitic, stearic, oleic, and linoleic acids; cerebrosides,
      sulfatides and two kinds of gangliosides are also found in the NDV membrane. It
      is reported for the first time in NDV that phospholipid classes are
      asymmetrically distributed over the two leaflets of the membrane: 60 +/- 4.5% of
      the phosphatidylcholine and 70 +/- 5.0% of the sphingomyelin are in the outer
      monolayer. Intact viral membranes and reconstituted NDV envelopes showed similar
      dynamic properties. Hemagglutinin-neuraminidase (HN) and fusion (F) proteins of
      NDV membrane affect the lipid thermotropic behaviour in reconstituted
      proteoliposomes made up of a single class of phospholipids. It is shown that the
      lipid composition is more important than the bulk membrane fluidity/order for
      both sialidase (neuraminidase) and hemagglutinating HN activities. Sialidase and
      hemagglutinating activities requires the presence of definite phospholipids
      (phosphatidylethanolamine) in its environment.

PMID- 9247164
TI  - Characterization and phase behaviour of phospholipid bilayers adsorbed on
      spherical polysaccharidic nanoparticles.
AB  - In this paper a new drug carrier, the Light-biovector, is described. These
      biovectors are composed of a neutral, anionic or cationic polysaccharidic core
      surrounded by phospholipids. They can be prepared with high yield and in a nearly
      pure form as determined by density analysis on sucrose gradients. These particles
      showed great stability with no sedimentation being observed after more than one
      year of storage. Physicochemical studies carried out with
      dipalmitoylphosphatidylcholine and
      dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol mixtures showed
      that in Light-biovectors, the lipids are organized in bilayer surrounding the
      polysaccharidic core. In presence of a neutral polysaccharidic core, the gel to
      liquid phase transition temperature Tm of DPPC was only slightly affected as
      compared to liposomal dispersions of the lipid. In contrast, for cationic and
      anionic Light-biovectors, the Tm of the lipids was affected by the electric
      charge born by the polysaccharidic core, indicating that electrostatic
      interactions contribute to the organization of the lipid bilayer in these
      systems. It was also found that the association of anionic membrane to anionic
      polysaccharidic cores and the association of cationic membrane to cationic
      polysaccharidic cores was possible.

PMID- 9247165
TI  - Solute-induced shift of phase transition temperature in Di-saturated PC
      liposomes: adoption of ripple phase creates osmotic stress.
AB  - We have examined the calorimetric behavior of large liposomes consisting of
      symmetric saturated chain phosphatidylcholines. Most notably, for systems made in
      solutions containing solute (e.g., NaCl, glucose, etc.) there was an additional
      major endotherm just below the main phase transition temperature. The new
      endotherm was found to represent a population of lipid whose main phase
      transition was shifted to lower temperature due to an induced osmotic stress
      across the membrane. Absent for isoosmotic systems, the osmotic stress was
      created when the liposome internal volume decreased, a consequence of the Lbeta'
      (gel) to Pbeta' (rippled) phase transition. That is, rippling of the membrane
      caused vesicle volume to decrease (> or = 28%) and because the free flow of water
      outward was restricted by solute, an osmotic gradient was created where none had
      existed before. The distribution of enthalpy between the new shifted Tm and the
      expected Tm correlated with the percent of lipid in the outer bilayer and it was
      concluded that only the outer bilayer sensed the induced stress. Internalized
      liposome structures were shielded, thus explaining the persistence of the
      expected Tm in preparations made in solute. The shift in Tm (deltaTm) was
      discrete and linearly dependent upon lipid chain length for the PC series di-17:0
      (deltaTm approximately 1.4 degrees C) through di-20:0 (deltaTm approximately 0.6
      degrees C), suggesting a structural change (i.e., lipid packing/orientation) was
      involved. Although freeze-fracture electron microscopy of stressed and unstressed
      bilayers revealed no differences in ripple periodicity there were differences in
      surface features and in vesicle shape. The fact that this phenomenon has gone
      unnoticed for MLVs is probably due to the fact that these systems are known to
      exclude solute and thus exist under osmotic compression.

PMID- 9247166
TI  - A calcium-activated, large conductance and non-selective cation channel in
      Paramecium cell.
AB  - A non-selective cation channel was found in mutant Paramecium cells (K115). This
      cell had been selected as a resistant mutant in a high-K+ solution. In patch
      clamp studies of these cells in the inside-out configuration, this channel was
      activated by bath applications of elevated Ca2+ concentrations. The channels
      became very active when the Ca2+ concentration was above 3.2 microM. The channel
      was also activated by depolarization. The voltage dependency was steep upon
      depolarization, whereas upon hyperpolarization the channel activity barely
      changed. This channel had poor selectivity for monovalent alkali cations. Using
      the Goldman-Hodgkin-Katz equation for the reversal potential, the permeability
      ratios with respect to K+ for Na+, Rb+, Cs+ and Li+ were nearly 1. Although the
      permeability ratios were similar for each cation, the single channel conductances
      differed. The single channel conductances were 467 pS with K+ as the charge
      carrier, 406 pS with Na+, 397 pS with Rb+, 253 pS with Cs+ and 198 pS with Li+
      upon depolarization in 100 mM cation solutions. A similar calcium-activated large
      conductance channel was observed in the wild-type (G3) Paramecium cells but was
      very rare.

PMID- 9247168
TI  - Fluorescent recovery after photobleaching (FRAP) of a fluorescent transferrin
      internalized in the late transferrin endocytic compartment of living A431 cells:
      theory.
AB  - In previous works, other authors characterized a compartment (LCT) of A431
      carcinoma cells in which markers of transferrin endocytose had accumulated during
      a long chase period. This compartment, was essentially formed by large stationary
      vacuoles. A few small vesicles budded from these vacuoles, rapidly saltated along
      microtubules and eventually fused with other vacuoles, causing an intracellular
      transport of the marker bound to the limiting membrane (M. De Brabander, R.
      Nuygens, H. Geerts, C.R. Hopkins, Cell. Mot. Cytoskel. 9 (1988) 30). In the
      present paper, we derived the fluorescence recovery after photobleaching (FRAP)
      of a fluorescent marker of LCT. We assumed that the rate of the intracellular
      transport of the marker was controlled by the fission-fusion process between
      vesicles and vacuoles. We showed that the concentration of a bleached fluorescent
      marker was a decreasing exponential function of the time elapsed from the
      beginning of the recovery phase. The rate constant of this exponential was equal
      to the product of the vesicle surface by the number of vesicles which fused with
      a unit of vacuole surface during one second. If a fraction of the marker
      spontaneously reactivated itself with a much higher rate constant of reaction
      than the rate constant of the transport process, the fractional FRAP of the
      marker was the sum of the fractional FRAP of both processes occurring separately.
      In a companion paper (F. Azizi, P. Wahl, Biochim. Biophys. Acta 1327 (1997) 75
      88), our FRAP experiments will be described and analysed with the mathematical
      expressions derived in the present paper.

PMID- 9247167
TI  - Combination of antitumor ether lipid with lipids of complementary molecular shape
      reduces its hemolytic activity.
AB  - Because the therapeutic use of the antitumor ether lipid 1-O-octadecyl-2-O-methyl
      sn-glycero-3-phosphorylcholine (ET-18-OCH3) is restricted by its hemolytic
      activity we explored the use of lipid packing parameters to reduce this toxicity
      by creating structurally optimized ET-18-OCH3 liposomes. We postulated that
      combination of ET-18-OCH3, which is similar in structure to
      lysophosphatidylcholine, with lipid molecules of complementary molecular shape
      (opposite headgroup/chain volume) would likely yield a stable lamellar phase from
      which ET-18-OCH3 exchange to red blood cell membranes would be curtailed. To
      quantitate the degree of shape complementarity, we used a Langmuir trough and
      measured the mean molecular area per molecule (MMAM) for monolayers comprised of
      ET-18-OCH3, the host lipids, and binary mixtures of varying mole percentage ET-18
      OCH3. The degree of complementarity was taken as the reduction in MMAM from the
      value expected based on simple additivity of the individual components. The
      greatest degree of shape complementarity was observed with cholesterol: the order
      of complementarity for the ET-18-OCH3-lipid mixtures examined was cholesterol >>
      DOPE > POPC approximately DOPC. Phosphorus NMR and TLC analysis of aqueous
      suspensions of ET-18-OCH3 (40 mol%) with the host lipids revealed them to all be
      lamellar phase. For ET-18-OCH3 at 40 mol% in liposomes, the hemolytic activity
      followed the trend of the reduction in MMAM and was least for the ET-18
      OCH3/cholesterol system (H50 = 661 microM ET-18-OCH3) followed by ET-18-OCH3/DOPE
      (H50 = 91 microM) and mixtures with POPC and DOPC which were comparable at H50 =
      26 microM and 38 microM, respectively: the H50 concentration for free ET-18-OCH3
      was 16 microM. This experimental strategy for designing optimized liposomes with
      a reduction in exchange, and hence toxicity, may be useful for other
      amphipathic/lipophilic drugs that are dimensionally compatible with lipid
      bilayers.

PMID- 9247169
TI  - Fluorescence recovery after photobleaching (FRAP) of a fluorescent transferrin
      internalized in the late transferrin endocytic compartment of living A431 cells:
      experiments.
AB  - In this work, we verified that transferrin fluorescently labelled with lissamine
      rhodamine sulfochloride (Tf-LRSC) is internalized in epidermoid A431 carcinoma
      cells through the specific endocytic pathway of transferrin. The FRAP of this
      fluorescent marker internalized in the late compartment of transferrin
      endocytosis (LCT) was measured in living A431 cells. These experiments showed the
      presence of an active intracellular transport of Tf-LRSC which can be interpreted
      by a mechanism involving carrier vesicles budding from stationary vacuoles,
      saltating along microtubules and fusing with other stationary vacuoles, according
      to previous video-microscopy observations of a membranous traffic dynamics in
      these cells, revealed by a gold complex of an Anti-Transferrin Receptor (ATR) (M.
      De Brabander, R. Nuygens, H. Geerst, C.R. Hopkins, Cell. Motil. Cystoskel. 9
      (1988) 30). When the A431 cells were treated with nocodazole or metabolic
      inhibitors, there remained a residual FRAP which was ascribed to the spontaneous
      reactivation of the bleached molecules. According to a theoretical result
      obtained in the companion paper (P. Wahl, F. Azizi, Biochim. Biophys. Acta 1327
      (1997) 69-74), we derived the fractional FRAP characterizing the transport
      process of Tf-LRSC by subtracting the fractional FRAP of the nocodazole-treated
      cells from the fractional FRAP of the non-treated cells. This FRAP of transport
      was fitted to a formula derived in that companion paper and based on the
      mechanism outlined above. From the time constant value determined by this fit,
      the number of vesicles which fused with a unit of vacuole surface was calculated
      to be 0.15 microm(-2) s(-1). The rate value of the fusion of vesicles with
      vacuoles was divided by two in cells treated by AlF4-, and increased to 20% in
      cells treated with Brefeldin A. These results correspond to an homotypic fusion
      process regulated by an heterotrimeric G-protein. Our work suggests that FRAP can
      be used to bring information on the transport of membrane components in living
      eukaryotic cells.

PMID- 9247170
TI  - Voltage sensitivity of gap junction currents in rat osteoblast-like cells.
AB  - The dependence of macroscopic gap junctional conductance (g(j)) upon
      transjunctional voltage (Vj) was examined in 39 paired osteoblast-like (OB) cells
      from primary cultures using the double whole cell patch clamp technique. OB cells
      were derived from calvarial explants of new-born rats. Instantaneous current
      voltage (Ij-Vj) relationships of OB cell pairs (n = 6) were linear in the entire
      voltage range (-150 < Vj < 150 mV) examined. The steady-state Ij-Vj relationship
      was non-linear for V > or = +/-60 mV. The curve for the normalised steady-state
      junctional conductance-voltage relationship (Gss/G0-Vj) was bell-shaped, and was
      fitted with a two-state Boltzmann equation with a minimum conductance (Gmin) of
      0.2-0.3, and a half deactivation voltage (Vo) of +/-83 mV. In two recordings
      unitary gap junction channel activity was observable. The linear I-V
      relationships revealed a single channel conductance of approximately 100 pS.
      Application of parathyroid hormone (10(-8) M) had no effect on the voltage
      dependence nor the magnitude of macroscopic currents (n = 7).

PMID- 9247171
TI  - Association and release of prostaglandin E1 from liposomes.
AB  - PGE1-lipid interactions were studied in several liposome systems. Data from both
      circular dichroic (CD) measurements and differential scanning calorimetry (DSC)
      indicated that PGE1 in the protonated form seeks the less polar environment of
      the lipid bilayer. CD measurements made on PGE1 in solution showed that the
      wavelength of maximum absorbance red shifted approximately 8 nm with decreasing
      solvent polarity. The CD spectrum of liposomal PGE1 prepared in pH 4.5 but not pH
      7.2 buffer was also red shifted. There was no red shift in the CD spectrum of
      PGE1 detected at pH 4.5 in the absence of phospholipid. DSC measurements on DSPC
      bilayers prepared with 5 mol% PGE1 at pH 4.5 but not pH 7.2 revealed an almost
      complete loss of the pre-transition as well as broadening of the main phase
      transition. The amount of 3H-PGE1 initially associated with EPC, POPC or DSPC
      liposomes was determined using size exclusion filters and centrifugation. This
      amount was found to be dependent on the pH of the buffer (pH 4.5 >> pH 7.2) and
      fluidity of the bilayer (EPC = POPC > DSPC), but independent of the lamellarity
      of the liposome. In all cases, addition of cholesterol reduced the amount of PGE1
      associated with the liposome. The time-dependent release of PGE1 from the
      liposomes was determined by rapidly diluting the sample 100-fold into pH 7.2
      buffer. Lipid saturation was a key factor influencing this release. Gel-phase
      liposomes of DSPC showed a rapid initial release (t(1/2) < 2 min) of PGE1,
      corresponding to the amount in the outer monolayer, followed by a very slow,
      almost negligible release of the remaining PGE1. A rapid initial release also
      occurred in fluid-phase membranes, followed by a more gradual release of the
      remaining PGE1 over several hours. This release rate could be slowed by
      increasing the lamellarity of these liposomes, or adding cholesterol to decrease
      the fluidity of the membrane.

PMID- 9247172
TI  - Purification of functional human P-glycoprotein expressed in Saccharomyces
      cerevisiae.
AB  - A system for expression and facile purification of the human P-glycoprotein (Pgp)
      from the yeast Saccharomyces cerevisiae is described. The wild-type human mdr1
      cDNA was cloned into a high copy number yeast expression vector under the control
      of the constitutive promoter of the yeast plasma membrane H+-ATPase. Western
      blots of membranes from the stable transformants confirmed that the Pgp is
      expressed in yeast cells in amounts approximately 0.4% of the total yeast
      membrane protein. Density gradient sedimentation analysis of the yeast membranes
      indicated that the expressed Pgp is localized in the plasma membrane. Yeast cells
      transformed with the Pgp expression plasmid acquire increased resistance to
      valinomycin, suggesting that the expressed Pgp is properly folded and functional.
      The expressed Pgp can be solubilized from the yeast membranes with
      lysophosphatidylcholine, and when tagged with ten histidines at its C-terminus,
      can be readily purified to about 90% homogeneity by Ni2+ affinity chromatography.
      About 50 microg of the Pgp can be purified from 20 mg of crude yeast membranes.
      The purified human Pgp exhibits a verapamil-stimulated ATPase activity and the
      maximal activity is 2.5 +/- 0.5 micromol/min per mg of Pgp, suggesting that the
      purified Pgp from yeast is highly functional. The Pgp expressed in yeast has the
      same electrophoretic mobility (ca. 130 kDa) as the Pgp produced in Sf9 insect
      cells and is unaffected by N-glycosidase treatment, suggesting that it is not
      glycosylated. Because of the relative ease of growing yeast in massive quantities
      this expression system appears to be excellent for producing this membrane
      transporter at levels sufficient for further biochemical and biophysical studies,
      and for site-directed mutagenesis studies as well.

PMID- 9247173
TI  - Interactions of an antimicrobial peptide, magainin 2, with outer and inner
      membranes of Gram-negative bacteria.
AB  - Magainin peptides, isolated from Xenopus skin, have broad spectra of
      antimicrobial activity and low toxicities to normal eukaryotic cells, thus being
      good candidates for therapeutic agents. The mechanism of action is considered to
      be the permeabilization of bacterial membranes. A number of studies using lipid
      vesicles have elucidated its molecular detail. However, their interactions with
      bacteria are not yet well understood. In this paper, we synthesized several
      magainin analogs with different charges (0 to +6) and hydrophobicities, and
      systematically studied their interactions with the outer and inner membranes of
      three species of Gram-negative bacteria (Escherichia coli, Acinetobacter
      calcoaceticus, Proteus vulgaris). The treatment of the E. coli cells with native
      magainin 2 (+4) immediately induced the efflux of the intracellular K+ ions and
      the cell death. A number of blebs were formed on the bacterial surface and the
      outer membrane became leaky. An increase in the peptide's positive charge
      enhanced the outer membrane permeabilization and the bactericidal activity. The
      cationic peptides also effectively permeabilized the inner membranes rich in
      acidic phospholipids, indicating the importance of electrostatic interactions.
      Substitution of Trp for Phe simultaneously increased the bactericidal activity
      and the hemolytic activity. A strategy to develop potent antimicrobial peptides
      was discussed on the basis of these results.

PMID- 9247175
TI  - Long-term ex vivo implantation (longer than one year) of rotary blood pumps.

PMID- 9247174
TI  - Phosphatidylcholine-fatty acid membranes: effects of headgroup hydration on the
      phase behaviour and structural parameters of the gel and inverse hexagonal
      (H(II)) phases.
AB  - The phase behaviour and structural parameters of a homologous series of saturated
      diacyl phosphatidylcholine/fatty acid 1:2 (mol/mol) mixtures having chain lengths
      from C12 to C20 were studied by X-ray diffraction and calorimetry, as a function
      of water content. The chain-melting transition temperatures of the 1:2 PC/FA
      mixtures are found to be largely independent of the degree of hydration. For all
      chain lengths, the tilted L(beta') and rippled P(beta') gel phases of the pure PC
      component are replaced by an untilted L(beta) gel phase in the 1:2 PC/FA
      mixtures. This gel phase swells considerably upon hydration, with a limiting
      water layer thickness in the range 18-24 A, depending on the chain length.
      However, unlike pure phospholipid systems, the lateral chain packing within the
      gel phase bilayers is essentially identical in both the dry and the fully
      hydrated states. The fluid bilayer L(alpha) phase is suppressed in the 1:2
      mixtures, being replaced by inverse non-lamellar phases for all chain lengths
      greater than C12, and at all levels of hydration. For chain lengths of C16 and
      greater, the inverse hexagonal H(II) phase is formed directly upon chain melting,
      at all water contents. For the shorter chain length mixtures, the behaviour is
      more complex, with the H(II) phase forming at low hydration, but with
      bicontinuous cubic phases appearing at higher levels of hydration. The
      implications of these surprising results are explored, in terms of the effective
      hydrophilicity of the associated PC and FA headgroups and the packing within the
      interfacial region. We suggest that the presence of the fatty acids significantly
      alters the lateral stress profile across the lipid monolayer in the fluid state,
      compared to that of the corresponding pure PC system, such that inverse phases,
      where the interface bends towards the water, become strongly favoured.
      Furthermore, for short chain lengths, packing constraints favour the formation of
      phases with negative interfacial Gaussian curvature, such as the bicontinuous
      cubic phases, rather than the H(II) phase, which has more severe chain packing
      frustration.

PMID- 9247176
TI  - New method to calculate creatinine generation rate using pre- and postdialysis
      creatinine concentrations.
AB  - The creatinine (Cr) generation rate reflects the muscle mass, a possible
      indicator of protein nutritional status. Thus, in this study, we developed
      equations for calculating the Cr generation rate. Depner and Daugirdas recently
      developed a method for determining the protein catabolic rate (PCR) from the pre-
      and postdialysis blood urea nitrogen concentrations. We modified their method to
      develop equations for calculating the total Cr generation rate from the measured
      predialysis Cr concentration and estimated postrebound concentration. The total
      Cr generation rate is defined as the sum of the intrinsic Cr generation rate and
      the extrinsic Cr generation rate (i.e., the generation rate of Cr derived from
      food). In the present study, the postrebound Cr concentration was estimated on
      the basis of postdialysis Cr concentration and the K/V for Cr. The intrinsic Cr
      generation rate was obtained by subtracting the extrinsic Cr generation rate,
      which was estimated on the basis of the PCR, from the total Cr generation rate
      calculated. The intrinsic Cr generation rate determined with this method was
      virtually the same as that obtained using the postrebound Cr concentration, the
      concentration immediately before the next hemodialysis (HD) session, and the PCR.
      The intrinsic Cr generation rate determined with the present method did not vary
      with changes in the HD prescription (i.e., with an increase in blood flow rate, a
      prolongation of the HD duration time, or a change in dialyzer membrane area). The
      present study also indicated that the intrinsic Cr generation rate decreased with
      age in both males and females.

PMID- 9247177
TI  - Modeling arterial hypotension during hemodialysis.
AB  - A mathematical model of the hemodynamic response to hemodialysis is presented.
      This model includes the dynamics of sodium, urea, and potassium in the
      intracellular and extracellular pools; fluid balance equations for the
      intracellular, interstitial, and plasma volumes; systemic and pulmonary
      hemodynamics; and the action of several short-term arterial pressure control
      mechanisms. The control mechanisms are triggered by information coming from both
      arterial and cardiopulmonary pressoreceptors, and they work on systemic arterial
      resistance, heart rate, and systemic venous unstressed volume. Moreover, the
      model hypothesizes that decreasing left atrial pressure below a given threshold
      causes a paradoxical withdrawal of the sympathetic drive and a consequent
      vasodepressor syncope. The model is used to simulate the pattern of the main
      hemodynamic quantities (systemic arterial pressure, heart rate, total systemic
      resistance, and cardiac output) during hemodialysis in several groups of patients
      (both hypotension resistant and hypotension prone) whose data were drawn from the
      clinical literature. The simulation results point out that the model is able to
      reproduce a variety of different conditions, including no hypotension, moderate
      hypotension, and severe hypotension with ultimate vasodepressor syncope, by
      adjusting a few parameters with clear physiological meanings. Hypotension is
      principally imputed to a loss of the sympathetic mechanisms working on systemic
      resistance and to an impairment of vascular refilling at the capillary wall. The
      results suggest that hypotension during hemodialysis is a complex phenomenon that
      depends on the superimposition of several concomitant factors working together
      that can lead to a variety of distinct individual patterns.

PMID- 9247178
TI  - Mathematical investigation of some physiological factors involved in hemodialysis
      hypotension.
AB  - A previously developed mathematical model is used to investigate the role of some
      hemodynamic, regulatory, and osmotic factors in the development of symptomatic
      hypotension during hemodialysis. Sensitivity analysis of the model parameters
      suggests that a decrease in atrial pressure, with a consequent fall in cardiac
      output (Frank-Starling mechanism), is the primary hemodynamic perturbation
      induced by ultrafiltration. Also, during the first hours of a hemodialysis
      session, the sympathetic mechanism working on systemic resistance is the main
      factor responsible for arterial pressure maintenance, and the physiological
      response is probably characterized by a prevalence of the cardiopulmonary over
      the arterial baroreflex control. During this period, a decrease in plasma
      osmolarity, caused mainly by urea removal, may contribute to the reduction of
      vascular refilling. During the last hours of the session, the arterial pressure
      level is also significantly affected by other factors that influence vascular
      refilling and mean circulatory filling pressure (systemic compliance; action of
      feedback mechanisms working on venous unstressed volume; plasma oncotic pressure;
      and, especially, capillary wall permeability and interstitial space elastance).
      Simulation of hemodialysis with different modalities emphasizes the importance of
      avoiding high ultrafiltration rates and of maintaining the sodium concentration
      in the dialysate close to the sodium concentration of the extracellular fluid to
      limit the risk of symptomatic hypotension. Higher values of sodium in the
      dialysate are, however, associated with poor sodium removal from the
      extracellular pool with risks of interdialytic morbidity. In the future, the
      model may be used to optimize the ultrafiltration rate and sodium profile in the
      dialysate according to individual patient prescriptions.

PMID- 9247179
TI  - Influence of blood flow on adsorption of beta2-microglobulin onto AN69 dialyzer
      membrane.
AB  - Adsorption onto the dialyzer membrane is a contributing factor to the elimination
      of beta2-microglobulin (beta2M) from the sera of uremic patients. The purpose of
      this prospective study was to ascertain the influence of the blood flow rate on
      adsorption of beta2M onto the polyacrylonitrile (AN69) hollow-fiber dialyzer
      membrane in 8 patients during regular hemodialysis (HD). Blood first passed
      through a low-flux polysulfone dialyzer and then through an AN69 dialyzer, which
      was not in contact with the dialysis fluid. During the investigation period
      (first hour of the HD session), the blood flow rate was 100 ml/ min (first part
      of the study), 200 ml/min (second part of the study), and 300 ml/min (third part
      of the study). Ultrafiltration was not performed during the investigation period.
      At the start of the HD sessions, the serum concentration of beta2M in the
      afferent blood line did not differ significantly among the 3 parts of the study.
      Serum beta2M was measured in samples taken from the afferent and efferent blood
      lines of the AN69 dialyzer at 5, 10, 15, 30, 45, and 60 min. The serum beta2M
      concentration decreased significantly in blood that had passed through the AN69
      dialyzer. This decrease, indicating membrane adsorption, was maximal during the
      first part and minimal during the third part of study. The decrease in the
      contact time between the blood and the AN69 could be the underlying cause. The
      calculated quantities of beta2M adsorbed onto the AN69 membrane (44.2 +/- 10.2,
      43.2 +/- 12.1, and 42.6 +/- 17.3 mg) did not differ significantly among the 3
      parts of the study. These results suggest that an increase in blood flow rate
      from 100 to 300 ml/min did not significantly affect the quantity of beta2M
      adsorbed onto the AN69 membrane.

PMID- 9247181
TI  - Hemodynamic performance of the St. Jude Medical Hemodynamic Plus valve.
AB  - The hemodynamic performance of the St. Jude Medical Hemodynamic Plus valve (HP)
      for a small aortic annulus was compared to that of the standard St. Jude Medical
      valve (SJM). Doppler echocardiographic parameters were evaluated in patients
      undergoing aortic valve replacement with either a 19 mm HP (HP19, n = 7), a 21 mm
      HP (HP21, n = 8), a 19 mm SJM (SJM19, n = 16), or a 21 mm SJM (SJM21, n = 34).
      The peak and mean pressure gradients and peak flow velocity were significantly (p
      < 0.05) lower in both patients with the HP21 and those with the HP19 than
      patients with the SJM21 and those with the SJM19, respectively. The
      echocardiographic parameters of the patients with the HP19 corresponded closely
      to those of patients with the SJM21. The left ventricular mass index regressed
      markedly in patients with the HP19 during the late postoperative period. The
      results suggested that the hemodynamic performances of certain sizes of the HP
      were superior to those of the same size SJMs and were considered to be equivalent
      to those of the next size larger SJM.

PMID- 9247180
TI  - The impact of polyethylene glycol conjugation on bovine hemoglobin's circulatory
      half-life and renal effects in a rabbit top-loaded transfusion model.
AB  - This study compares the effects of polyethylene glycol (PEG) modified bovine
      hemoglobin on vascular half-life and renal function in rabbits to those of
      unmodified bovine hemoglobin. Renal function was assessed by the measurement of
      the glomerular filtration rate, urinalysis, blood chemistries, hemoglobin (Hb)
      excretion rates, and tissue histology. The influence of infusion rates on
      hemoglobin excretion rates and organ morphology was also examined. The mean half
      life of unmodified bovine hemoglobin was 3.0 +/- 0.1 (mean +/- SEM) h, which was
      extended 14-fold to 43.2 +/- 1.7 h following PEG conjugation. The glomerular
      filtration rate, urinalysis, and blood chemistries were not greatly affected by
      either the unmodified bovine hemoglobin or the PEG modified bovine hemoglobin.
      However, unmodified bovine hemoglobin did demonstrate significant hemoglobinuria
      (Hb excretion levels in excess of 1.0% of the infused dose [p < 0.05]) at all
      infusion rates given while PEG modified bovine hemoglobin did not. In addition,
      histological examination by light microscopy indicated that the most severe
      morphological changes occurred in animals that received unmodified bovine
      hemoglobin. This data suggests that PEG modification of bovine hemoglobin
      significantly reduced some of the adverse effects of bovine hemoglobin on renal
      physiology and morphology.

PMID- 9247182
TI  - The importance of pulsatile and nonpulsatile flow in the design of blood pumps.
AB  - The traditional approach of total artificial heart (TAH) and ventricular assist
      device (VAD) development has been the mimicking of the native heart. Nonpulsatile
      flow using cardiopulmonary bypass has provided evidence of short-term physiologic
      tolerances. The design of nonpulsatile TAHs and VADs has eliminated the need for
      valves, flexing diaphragms, and large ventricular volumes. However, these devices
      require high efficiency power sources and reliable bearing seals or
      electromagnetic bearings while simultaneously attempting to avoid thromboemboli.
      The physiologic response to nonpulsatile flow is complex and variable. When
      compared to a pulsatile device, a nonpulsatile TAH or VAD needs to produce
      increased flow and higher mean intravascular pressures to maintain normal organ
      function. Despite its maintaining normal organ function, nonpulsatile flow does
      cause alterations in biochemical functions and organ specific blood flow. The
      combination of bioengineering superiority and the maintenance of physiologic
      homeostasis has directed future TAH and VAD research towards nonpulsatile
      systems.

PMID- 9247183
TI  - Blood supply to the latissimus dorsi muscle and muscle performance during co- or
      counterpulsatile stimulation for circulatory assist.
AB  - For the application of the latissimus dorsi muscle (LDM) to circulatory assist,
      the muscle is stimulated with co- or counterpulsation during the cardiac cycle.
      The purpose of this study was to evaluate the blood supply to the LDM and its
      muscular performance during each respective stimulation. The origin of the LDM
      was connected to a tension gauge, a potentiometer, and 1 kg of weight in series.
      The LDM was stimulated at a ratio of 1:1 of heart to muscle contraction for 10
      min. Copulsatile stimulation made thoracodorsal arterial flow (TDF) predominant
      during cardiac diastole. In counterpulsatile stimulation, TDF occurred
      predominantly during cardiac systole. Between the 2 patterns of stimulation, no
      significant differences were observed in the mean TDF rate during 1 cardiac
      cycle. The maximal force, maximal contraction length, and power of the LDM also
      did not differ significantly. These results suggest that despite the difference
      of the TDF profile, LDM performance may be comparable between co- and
      counterpulsatile stimulation for the application of the LDM to circulatory
      assist.

PMID- 9247184
TI  - In vivo comparison of two enteric-pouch power transformers for circulatory
      support.
AB  - A defunctionalized ileal pouch is thin-walled (1-2 mm), well perfused (blood
      flow, 0.3-1.0 ml/g/min), and tactile-insensitive. If fixed within the abdominal
      wall and provided with a miniature stoma for primary wire entry, the heat
      dissipating capacity and achievable geometries could facilitate small efficient
      intra- to extracorporeal power transformers with virtually complete magnetic flux
      containment. Two transformers (A, weighing 102 gm with dual ferrite cores,
      intraluminal primary and extraluminal secondary each with 10 turns on its own
      crescentic ferrite core, 90 kHz, coupling coefficient k = 0.90-0.96; and B, 68
      gm, a single flexible torroidal magnetic metallic tape core with attached 11 turn
      primary and free 14 turn serosal secondary, 14.7 kHz, k = 0.99) met the
      electrical and anatomic requirements. Each was implanted (minilaparotomy, coil
      pouch fixation within abdominal musculature) in 4 dogs for 14-21 days to test the
      operative feasibility, electrical function, warming, and flux containment. For
      canine testing, wires were tunneled to a chewing-inaccessible site. Neither
      tissue necrosis, infection, provokable interference from contiguous metal, nor
      coil displacement were observed; secretions were retained in Group A pouches
      only. The mean power transmissions for the transformers were A: 24.90 +/- 1.50 W
      and B: 24.92 +/- 0.89 W, after operation for 7 days or more. The mean
      efficiencies were A: 75.6 +/- 0.1% total DC/DC, 96.2% coils and B: 80.4 +/- 0.1%
      total DC/DC, 96.2% coils. The peak skin surface magnetic fluxes for transformers
      A and B, both trivial at 1.7 and 1.2 G, respectively, were similar. Warming was
      0.62 +/- 0.30 degrees C in Group A and 0.73 +/- 0.19 degrees C in Group B. The
      probability values were p < 0.5 (NS) for DC/DC efficiency and p > 0.10 (NS), for
      A versus B in all other areas of comparison. Observations for both were
      encouraging. Transformer B, with less mass, lower frequency, higher efficiency,
      and intrinsic invulnerability to displacement, was selected for longer term
      evaluation.

PMID- 9247185
TI  - In vitro investigation of the St. Jude Medical Isoflow centrifugal pump: flow
      visualization and hemolysis studies.
AB  - Centrifugal blood pumps have become valuable therapeutic tools for
      cardiopulmonary bypass surgery. In addition, surgeons have used them as temporary
      ventricular assist devices, and this type of pump is also being developed for use
      as a permanent assist device and total artificial heart. However, centrifugal
      pumps create flow patterns that are significantly different from those the blood
      experiences physiologically. The St. Jude Medical Isoflow centrifugal pump has
      been used clinically during cardiopulmonary bypass surgery, yet no experimental
      results have been reported that describe the flow patterns within this pump or
      that quantify the hemolysis generated over a range of operating conditions. The
      purpose of this study was to investigate the flow patterns and hemolysis during 4
      operating conditions. The experimental operating conditions included the design
      condition (6 L/min, 2,500 rpm, 350 mm Hg), a high flow condition (10 L/min, 2,500
      rpm, 330 mm Hg), a low flow condition (2 L/min, 2,500 rpm, 370 mm Hg), and a near
      surge condition (2 L/min, 3,000 rpm, 550 mm Hg). The flow visualization results
      demonstrated that the flow within the impeller was well aligned with the impeller
      blades except near the inlet at the high flow condition. In contrast, the flow
      through the outlet was well aligned at the high flow condition while there was
      evidence of particle impact at the design condition, and the flow was disturbed
      at the low flow and near surge conditions. The indices of hemolysis (IH) for the
      3 operating conditions at 2,500 rpm were 0.0082 +/- 0.0026 (mean +/- SD) for the
      design condition, 0.0035 +/- 0.0014 for the high flow condition, and 0.0326 +/-
      0.0050 for the low flow condition. The indices for high and low flow were
      significantly different from that for the design condition (p < 0.05). The IH for
      the near surge condition (0.0748 +/- 0.0039) was significantly higher than that
      for all other conditions (p < 0.05). In addition to describing the flow patterns
      within the Isoflow, this study independently validated St. Jude Medical's
      reported IH at the design condition and showed how that IH significantly changed
      based on operating conditions.

PMID- 9247186
TI  - Mapping of pump efficiency on the pressure-flow curve of a centrifugal blood
      pump.
AB  - Because pump efficiency is closely related to heat generation and blood trauma in
      a centrifugal blood pump, it is quite important to study pump efficiencies in a
      variety of conditions. In the present study, pump efficiencies were mapped on the
      pressure head-flow rate curves of 4 different pumps; BioMedicus BioPump (BP-80),
      Nikkiso (NK), Gyro C1E3, and Gyro PI601 (diameter of the impeller, NK: 50 mm,
      C1Ee3: 65 mm, and PI601: 50 mm). The mapping of pump efficiency revealed the
      following findings. First, the cone type (BP-80) has less pump efficiency than
      the impeller type (NK and C1E3); second, the miniaturization of the C1E3 to the
      PI601 has resulted in an increase in pump efficiency; and third, the diameter of
      the impeller may contribute to the pump efficiency of an im peller type pump. The
      mapping of the pump efficiency, as demonstrated in this study, is useful for the
      analysis of hydraulic pump performance in a wide range of clinically applied
      conditions.

PMID- 9247187
TI  - Moving actuator type total artificial heart with reverse position of the aortic
      and pulmonary conduits.
AB  - Adequate intrathoracic anatomical compatibility is one of the most important
      considerations in designing a fully implantable total artificial heart (TAH). We
      have recently developed an innovative concept of reverse positioning of the
      aortic and pulmonary conduits to facilitate anatomical compatibility of the
      moving actuator type TAH. The pulmonary conduit of this TAH is designed to be
      located posterior to the aortic conduit, which results in a substantial reduction
      in the anteroposterior diameter of this heart, as well as the virtual elimination
      of the compression of the low pressure pulmonary conduit. In ovine orthotopic
      implantation experiments with this model of the TAH, we consecutively achieved 3
      day survival in 1 sheep and 2 day survival in another. To the best of our
      knowledge, these were the first significant short-term survival cases in the
      orthotopic implantation of electric TAHs in sheep.

PMID- 9247188
TI  - The mouse transcription factor Stat4 is expressed in haploid male germ cells and
      is present in the perinuclear theca of spermatozoa.
AB  - STAT (signal transducer and activator of transcription) proteins have been shown
      to be essential transcription factors which mediate biological effects of
      cytokines. Although most of the STATs have been shown to be widely expressed,
      Stat4 mRNA has been detected in only a few tissues, including the testis. In the
      present study, immunoblot analysis confirmed that the presence of Stat4 protein
      was similarly restricted, with the highest level observed in testis. In situ
      hybridization, immunoblot, and immunohistochemistry analyses revealed that in the
      testis, Stat4 was abundantly and exclusively expressed in male germ cells which
      have completed meiosis, at the round and elongating spermatid stages.
      Cytolocalization at various times of spermatid differentiation showed that the
      level of Stat4 protein increased in parallel in both cytoplasm and nuclei. No
      specific nuclear translocation that would have been an indicator of Stat4
      activation was observed at any stage of spermatogenic differentiation.
      Interestingly, the Stat4 transcription factor was localized to the condensing
      perinuclear theca of spermatids, a localization that was confirmed by selective
      biochemical extraction of thecal proteins. Since the theca is known to
      depolymerize in the cytoplasm of the oocyte during the hours following
      fertilization, we hypothesized that sperm Stat4 would represent an original
      paternal contribution to the fertilized egg which may be involved in the onset of
      zygotic transcription.

PMID- 9247189
TI  - In vitro exocytosis in sea urchin eggs requires a synaptobrevin-related protein.
AB  - Sea urchin eggs provide an efficient in vitro model of exocytosis. We have
      identified proteins in sea urchin eggs that cross-react with antibodies to
      mammalian synaptobrevin, synaptotagmin, SNAP-25, syntaxin and rab3a. We show that
      these proteins are localized to the sea urchin egg cortex, using western blotting
      and immunocytochemistry. Tetanus toxin light chain cleaves the synaptobrevin
      related protein in vitro and inhibits calcium-induced exocytosis. These data
      demonstrate a conservation between phyla of protein sequence and molecular
      mechanisms thought to facilitate exocytosis and show that the sea urchin egg
      provides a unique in vitro exocytotic model with which to study the conserved
      protein machinery of membrane fusion during secretion.

PMID- 9247190
TI  - Involvement of the rfp tripartite motif in protein-protein interactions and
      subcellular distribution.
AB  - The ret finger protein (rfp) is a member of the B box zinc finger gene family
      which possesses a tripartite motif consisting of a RING finger, B box finger, and
      a coiled-coil domain. Rfp is expressed at specific stages of spermatogenesis and
      in various adult mouse and human tissues. It becomes oncogenic when the
      tripartite domain is recombined with the tyrosine kinase domain of the ret
      protooncogene. Many of the B box family proteins function as homodimers, although
      the role of the individual components of the tripartite motif in this process
      remains unclear. We demonstrate that rfp homomultimerization occurs through the
      coiled-coil domains; however, while the B box is not an interacting interface
      itself, its structural integrity is necessary for this interaction to occur. This
      is the first evidence that the B box zinc finger domain is involved in regulating
      protein-protein interactions. Interestingly, we find that mutations of the RING
      finger and B box affect the subcellular compartmentalization of rfp in various
      cell lines. These results demonstrate that the interactions of rfp with itself
      and its association with specific subcellular compartments is dependent upon the
      function of all of the components of the tripartite motif. It is likely that
      these domains play a crucial role in the function of the rfp protein in normal
      cell differentiation and in its transformation potential in the recombined state.

PMID- 9247191
TI  - Two proteins that cycle asynchronously between centrosomes and nuclear
      structures: Drosophila CP60 and CP190.
AB  - Both the nucleus and the centrosome are complex, dynamic structures whose
      architectures undergo cell cycle-specific rearrangements. CP190 and CP60 are two
      Drosophila proteins of unknown function that shuttle between centrosomes and
      nuclei in a cell cycle-dependent manner. These two proteins are associated in
      vitro, and localize to centrosomes in a microtubule independent manner. We
      injected fluorescently labeled, bacterially expressed CP190 and CP60 into living
      Drosophila embryos and followed their behavior during the rapid syncytial
      blastoderm divisions (nuclear cycles 10-13). Using quantitative 3-D wide-field
      fluorescence microscopy, we show that CP190 and CP60 cycle between nuclei and
      centrosomes asynchronously with the accumulation of CP190 leading that of CP60
      both at centrosomes and in nuclei. During interphase, CP190 is found in nuclei.
      Immediately following nuclear envelope breakdown, CP190 localizes to centrosomes
      where it remains until telophase, thereafter accumulating in reforming nuclei.
      Unlike CP190, CP60 accumulates at centrosomes primarily during anaphase, where it
      remains into early interphase. During nuclear cycles 10 and 11, CP60 accumulates
      in nuclei simultaneous with nuclear envelope breakdown, suggesting that CP60
      binds to an unknown nuclear structure that persists into mitosis. During nuclear
      cycles 12 and 13, CP60 accumulates gradually in nuclei during interphase,
      reaching peak levels just before nuclear envelope breakdown. Once in the nucleus,
      both CP190 and CP60 appear to form fibrous intranuclear networks that remain
      coherent even after nuclear envelope breakdown. The CP190 and CP60 networks do
      not co-localize extensively with each other or with DNA. This work provides
      direct evidence, in living cells, of a coherent protein network that may
      represent a nuclear skeleton.

PMID- 9247192
TI  - Novel alphaGalNAc containing glycans on cytokeratins are recognized invitro by
      galectins with type II carbohydrate recognition domains.
AB  - We report on a novel posttranslational modification of cytoplasmic proteins.
      Presented evidences suggest that cytokeratins are bound in vitro by mammalian
      galectin-3 and the galectins from the sponge Geodia cydonium via their type II
      carbohydrate recognition domains, whose highest binding affinity is directed
      towards terminal alpha-N-acetylgalactosamine-bearing glycans with the general
      sequence GalNAcalpha1-3Gal(NAc)beta. Specificity analyses and the
      characterization of the critical sugar residue on cytokeratins for galectin
      binding were done with cytochemical and biochemical methods using various plant
      and animal lectins. Binding of GalNAc-specific lectins was saturable, sensitive
      to mild periodate oxidation, inhibitable by glycoconjugates carrying terminal
      GalNAc, and abolished after treatment of the cytokeratins with alpha-N
      acetylgalactosaminidase. Binding to bacterially expressed recombinant
      cytokeratins did not exceed background binding. The presence of GalNAc residues
      on highly purified cytokeratins from MCF-7 and HeLa SS6 cells was confirmed by
      sugar composition analyses using gas chromatography/mass spectrometry. This novel
      posttranslational modification was not restricted to cytokeratins of MCF-7 cells,
      but did also occur in all of 9 other examined human carcinoma cell lines and in a
      normal human mammary epithelial cell line. From these cytochemical and
      biochemical in vitro studies we hypothesize that this glycan with its terminal
      alpha1-3 linked GalNAc determinant might represent the first natural cytoplasmic
      ligand for endogenous galectins-3 detected so far.

PMID- 9247193
TI  - A programmed oxyradical burst causes hatching of mouse blastocysts.
AB  - The emergence of the mammalian blastocysts from their thick glycoprotein
      investment known as the zona pellucida is an important, but poorly understood,
      event in embryogenesis. In this paper, we demonstrate that peri-hatching
      blastocysts generate a considerably high quantum of an active oxyradical species
      for an extremely short period of time when compared to the pre-hatching
      (unhatched) and post-hatching (hatched) blastocysts. Hatching could be induced in
      pre-hatching blastocysts by exposing them to superoxide artificially generated to
      match the observed peri-implantation stage specific levels of superoxide, without
      impairing their viability. These observations suggest the operation of a
      superoxide-dependent hatching initiation in developing mammalian embryos.

PMID- 9247194
TI  - Occludin as a possible determinant of tight junction permeability in endothelial
      cells.
AB  - Endothelial cells provide a crucial interface between blood and tissue
      environments. Free diffusion of substances across endothelia is prevented by the
      endothelial tight junction, the permeability of which varies enormously depending
      on tissue. Endothelial cells of the blood-brain barrier possess tight junctions
      of severely limited permeability, whereas those of non-neural tissue are
      considerably leakier, but the molecular basis for this difference is not clear.
      Occludin is a major transmembrane protein localizing at the tight junction. In
      this study, we show, by immunocytochemistry, that occludin is present at high
      levels and is distributed continuously at cell-cell contacts in brain endothelial
      cells. In contrast, endothelial cells of non-neural tissue have a much lower
      expression of occludin, which is distributed in a discontinuous fashion at cell
      cell contacts. The apparent differences in occludin expression levels were
      directly confirmed by immunoblotting. The differences in occludin protein were
      reflected at the message level, suggesting transcriptional regulation of
      expression. We also show that occludin expression is developmentally regulated,
      being low in rat brain endothelial cells at postnatal day 8 but clearly
      detectable at post-natal day 70. Our data indicate that regulation of occludin
      expression may be a crucial determinant of the tight junction permeability
      properties of endothelial cells in different tissues.

PMID- 9247195
TI  - NNF1 is an essential yeast gene required for proper spindle orientation,
      nucleolar and nuclear envelope structure and mRNA export.
AB  - The nuclear envelope is central to nuclear structure and function. It plays a
      role in maintaining nuclear shape, allowing the exchange of macromolecules
      between the nucleus and the cytoplasm (via the nuclear pore complexes), and
      providing attachment sites for microtubules during chromosome segregation and
      nuclear migration (via the spindle pole body). We have isolated an essential
      yeast gene, NNF1 that is required for a number of nuclear functions. Cells
      depleted of Nnf1p or containing a temperature-sensitive nnf1 mutation have
      elongated microtubules and become bi- and multinucleate. They also have a
      fragmented nucleolous and accumulate poly(A)+ RNA inside the nucleus. A similar
      constellation of phenotypes has been reported in cells carrying mutations in a
      number of nuclear pore proteins, components of the Ran GTPase cycle, and the
      nuclear localization sequence receptor protein. Our results suggest that Nnf1p
      plays a role in a number of nuclear functions.

PMID- 9247196
TI  - Arachidonic acid stimulates protein kinase C-epsilon redistribution in heart
      cells.
AB  - Arachidonic acid is elevated in a variety of cell types in response to
      extracellular stimuli, and has been hypothesized to exert at least some of its
      intracellular actions via activation of protein kinase C. Here we show that
      arachidonic acid stimulates a unique pattern of translocation of the epsilon
      isoform of protein kinase C in isolated adult rat cardiac myocytes. Using western
      blot analysis, the majority of epsilon-protein kinase C was found in a cytosolic
      fraction in unstimulated cells. Treatment with 50 microM arachidonic acid caused
      a transient increase of epsilon-protein kinase C in a membrane fraction within 1
      minute, then after 5-20 minutes most was found in a filament/nuclear fraction.
      Immunofluorescence and confocal microscopy of the filament fraction revealed a
      striated staining pattern with epsilon-protein kinase C localized near the Z-line
      where actin filaments are anchored and where transverse tubules are closely
      apposed to the myofilaments. delta-Protein kinase C, another isoform highly
      expressed in these cells, did not redistribute significantly in response to
      arachidonic acid, but in response to phorbol ester displayed a predominantly
      nuclear localization. Arachidonic acid also stimulated phosphorylation of the
      thin filament protein, troponin I, consistent with a filament localization for
      activated PKC. The physiological relevance of these findings was supported by the
      observation that 50 microM arachidonic acid promoted a 2.3-fold enhancement of
      myocyte twitch amplitude, an effect that was significantly blocked by the protein
      kinase C antagonist chelerythrine. Moreover, the onset of this physiological
      response correlated in time with translocation of epsilon-protein kinase C to the
      filaments. The results suggest that arachidonic acid initiates a redistribution
      of epsilon-protein kinase C to myofilament structures at or near the Z-line where
      this isozyme would be strategically located to regulate myofilament function and
      excitation-contraction coupling.

PMID- 9247197
TI  - Clusterin/ApoJ expression is associated with neuronal apoptosis in the olfactory
      mucosa of the adult mouse.
AB  - The molecular events orchestrating neuronal degeneration and regeneration remain
      poorly understood. Attempts at identifying genes specifically expressed during
      these processes, have constantly led to the (re)isolation of the clusterin/ApoJ
      gene, whose expression is highly reactive to injury in a wide variety of tissues.
      To get insight into the function of clusterin in neuron loss, we have assessed in
      detail the clusterin gene expression in an experimental model of
      neurodegeneration, using the peripheral olfactory system of adult mouse. The
      sensory neurons of olfactory nasal mucosa can be massively induced to degenerate
      in vivo, by surgical removal of their only synaptic target: the olfactory bulb.
      We have previously shown that this neuron loss results from a near-synchronized
      induction of apoptosis genetic programs. We present here evidence that clusterin
      gene expression is tightly correlated to the onset of neuronal apoptoses in
      lesioned olfactory mucosae. The simultaneous preparation of DNA and RNA from the
      same tissue samples reveals that a strong clusterin mRNA accumulation coincides
      with the wave of nucleosome-sized DNA fragmentation. However, double detection of
      apoptotic nuclei by the TUNEL method and of clusterin messengers by in situ
      hybridization revealed that the clusterin gene expression is not induced in dying
      neurons, but in the glial sheath surrounding the axon bundles of degenerating
      olfactory neurons. Clusterin immunocytochemistry reveals that the clusterin
      protein accumulates not only in these producing cells, but also in the olfactory
      epithelium, suggesting the possibility of clusterin internalization by cells
      located at a distance from the synthesis loci. In view of this localization and
      of the activities of the clusterin protein reported so far, possible functions of
      clusterin in nervous plasticity are discussed.

PMID- 9247198
TI  - A genetic screen reveals a role for the late G1-specific transcription factor
      Swi4p in diverse cellular functions including cytokinesis.
AB  - The transcription factor Swi4p plays a crucial role in the control of the
      initiation of the cell cycle in budding yeast. To further understand Swi4p
      function, we set up a synthetic lethal screen for genes interacting with SWI4.
      Fourteen conditional mutations which resulted in lethality only in the absence of
      SWI4 have been isolated. Only two of them were suppressed by ectopic expression
      of CLN2, indicating that Swi4p is involved in diverse cellular processes in
      addition to its requirement for CLN1,2 regulation. In most of the mutants a cell
      cycle phenotype was observed, including defects in G1 progression, budding, the
      G2/M transition and cytokinesis. In addition, four of the mutations resulted in
      massive cell lysis at the restrictive temperature, indicating that Swi4p is
      involved in the maintenance of cell integrity. One of the mutants, rsf1
      swi4delta, was characterized in detail and it is defective in cytokinesis at the
      restrictive temperature. Staining with Calcofluor revealed that the rsf1
      swi4delta mutant is impaired in chitin biosynthesis. rsf1 is allelic to the AGM1
      gene, coding for N-acetylglucosamine-phosphate mutase, an enzyme involved in the
      biosynthesis of chitin. A single copy of SWI4 suppressed the cytokinesis defect.
      The above data suggest that Swi4p has a role in cytokinesis and becomes essential
      in this process when chitin biosynthesis is compromised. As overexpression or
      ectopic expression of CLN did not suppress the rsf1 swi4delta mutant phenotype,
      Swi4p must control some other gene(s) involved in cytokinesis.

PMID- 9247199
TI  - Cytosolic phospholipase A2 is activated by the hepatocyte growth factor receptor
      kinase in Madin Darby canine kidney cells.
AB  - The hepatocyte growth factor/scatter factor (HGF/SF) receptor which is a
      transmembrane protein encoded by the Met oncogene, possesses intrinsic tyrosine
      kinase activity which transduces the mitogenic, morphogenic and the scattering
      effect of HGF/SF. The pluripotent signal of HGF/SF is transduced through
      association of the Met receptor with various intracellular adaptors.
      Phosphorylation of cytosolic phospholipase A2 (cPLA2) is associated with
      activation of this molecule which in turn leads to arachidonic acid production
      followed by release of prostaglandins and related compounds exerting their roles
      onto cell proliferation, chemotaxis and vascular motility. Arachidonic acid and
      its metabolites were shown to be involved in processes like liver regeneration
      where growth factor receptors possessing tyrosine kinase activity are implicated.
      In this study we examined whether stimulation of the HGF/SF-receptor's tyrosine
      kinase activity would involve changes in the phosphorylation state and the
      activity of cPLA2 in MDCK cells, where HGF/SF is known to induce scattering
      responses rather than mitogenesis. The activated p145betaMET was shown to
      associate with and to phosphorylate cPLA2 on tyrosine residues, this leading to
      subsequent release of arachidonic acid. cPLA2 was also phosphorylated in serine
      residues and such a role has been so far assigned to the mitogen activated
      protein (MAP) kinase. Our data have also shown that MAP kinase is associated and
      phosphorylated on tyrosine by the activated p145betaMET. Immunodepletion of MAP
      kinase via electroporation of an anti-MAP kinase antibody, did not significantly
      decrease arachidonic acid release in HGF/SF-stimulated MDCK cells. It is
      therefore emerging that phosphorylation of cPLA2 on tyrosine by the HGF/SF
      receptor kinase is capable of triggering arachidonic acid release and that MAP
      kinase is contributing to full, but does not drive, the activity of cPLA2. The
      release of arachidonic acid by MDCK cells following HGF/SF stimulation is
      establishing this fatty acid and its metabolites as major components involved in
      the transduction of MET-driven signals and at the same time in the amplification
      of such signals.

PMID- 9247200
TI  - HSP70 and HSP90 homologs are associated with tubulin in hetero-oligomeric
      complexes, cilia and the cortex of Tetrahymena.
AB  - We show in the present study that homologs of hsp90 and hsp70 are induced by heat
      shocks in Tetrahymena and appear to form a high molecular mass complex
      (approximately 700 kDa) with tubulin. Three members of the hsp70 family (hsp72,
      73, and 78) and one member of the hsp90 family (hsp82) have been identified by
      immunological or by a combination of immunological and sequencing methods. The
      known components of the 700 kDa complex and the conditions under which it can be
      recovered suggest that it may be an induced protective assemblage rather than a
      normal processing intermediate. Immunoblotting and immunofluorescence studies
      suggest further that large amounts of hsp73 and lesser amounts of hsp82 are
      associated with mature microtubules in both cilia and the cortex in this cell
      type. Some site-specific localizations of the identified heat shock proteins were
      also noted in non-microtubular components of the cell cortex.

PMID- 9247201
TI  - The neural crest population responding to endothelin-3 in vitro includes
      multipotent cells.
AB  - The peptide endothelin 3 (EDN3) is essential for normal neural crest development
      in vivo, and is a potent mitogen for quail truncal crest cells in vitro. It is
      not known which subpopulations of crest cells are targets for this response,
      although it has been suggested that EDN3 is selective for melanoblasts. In the
      absence of cell markers for different precursor types in the quail crest, we have
      characterised EDN3-responsive cell types using in vitro colony assay and clonal
      analysis. Colonies were analysed for the presence of Schwann cells, melanocytes,
      adrenergic cells or sensory-like cells. We provide for the first time a
      description of the temporal pattern of lineage segregation in neural crest
      cultures. In the absence of exogenous EDN3, crest cells proliferate and then
      differentiate. Colony assay indicates that in these differentiated cultures few
      undifferentiated precursors remain and there is a low replating efficiency. By
      contrast, in the presence of 100 ng/ml EDN3 differentiation is inhibited and most
      of the cells maintain the ability to give rise to mixed colonies and clones
      containing neural crest derivatives. A high replating efficiency is maintained.
      In secondary culture there was a progressive decline in the number of cell types
      per colony in control medium. This loss of developmental potential was not seen
      when exogenous EDN3 was present. Cell type analysis suggests two novel cellular
      targets for EDN3 under these conditions. Contrary to expectations, one is a
      multipotent precursor whose descendants include melanocytes, adrenergic cells and
      sensory-like cells; the other can give rise to melanocytes and Schwann cells. Our
      data do not support previous claims that the action of EDN3 in neural crest
      culture is selective for cells in the melanocyte lineage.

PMID- 9247202
TI  - Absence of chronic effect of exposure to short-wave radio broadcast signal on
      salivary melatonin concentrations in dairy cattle.
AB  - A pilot study was conducted to investigate the influence of electromagnetic
      fields in the short-wave range (3-30 MHz) radio transmitter signals on salivary
      melatonin concentration in dairy cattle. The hypothesis to be tested was whether
      EMF exposure would lower salivary melatonin concentrations, and whether removal
      of the EMF source would be followed by higher concentration levels. For this
      pilot study, a controlled intervention trial was designed. Two commercial dairy
      herds at two farms were compared, one located at a distance of 500 m (exposed),
      the other at a distance of 4,000 m (unexposed) from the transmitter. At each
      farm, five cows were monitored with respect to their salivary melatonin
      concentrations over a period of ten consecutive days. Saliva samples were
      collected at two-hour intervals during the dark phase of the night. As an
      additional intervention, the short-wave transmitter was switched off during three
      of the ten days (off phase). The samples were analyzed using a radioimmunoassay.
      The average nightly field strength readings were 21-fold greater on the exposed
      farm (1.59 mA/m) than on the control farm (0.076 mA/m). The mean values of the
      two initial nights did not show a statistically significant difference between
      exposed and unexposed cows. Therefore, a chronic melatonin reduction effect
      seemed unlikely. However, on the first night of re-exposure after the transmitter
      had been off for three days, the difference in salivary melatonin concentration
      between the two farms (3.89 pg/ml, CI: 2.04, 7.41) was statistically significant,
      indicating a two- to seven-fold increase of melatonin concentration. Thus, a
      delayed acute effect of EMF on melatonin concentration cannot completely be
      excluded. However, results should be interpreted with caution and further trials
      are required in order to confirm the results.

PMID- 9247203
TI  - Effect of various acute 60 Hz magnetic field exposures on the nocturnal melatonin
      rise in the adult Djungarian hamster.
AB  - Acute exposure to a 1 Gauss 60 Hz magnetic field for 15 min beginning 2 hr before
      darkness delays and blunts the nighttime melatonin rhythm in some but not all
      studies. To determine whether other exposure parameters (dose, mode, or time)
      influence the nocturnal melatonin rise, adult Djungarian hamsters reared in long
      days (16L:8D, lights off at 1000-1800 hr) were acutely exposed to a 60 Hz
      continuous magnetic field (15 min of 1 or 0.1 Gauss) beginning 4 hr before or 4
      hr after lights off. Other hamsters were exposed to a 60 Hz intermittent magnetic
      field (15 or 60 min of a 1 Gauss field, 1 min on then 1 min off) between 1 and 2
      hr before lights off. In sham-exposed controls, i.e., hamsters simultaneously
      placed in an adjacent coil system but without current, pineal and serum melatonin
      concentrations increased from a low baseline (1 hr after lights off) to
      concentrations that were typical of the nighttime peak by 3 hr after darkness.
      Acute exposure to the 0.1 or 1 Gauss continuous magnetic field for 15 min at
      either 4 hr before or 4 hr after lights off did not disrupt the nocturnal rise in
      pineal or serum melatonin. Similarly, onset of the melatonin rhythm was not
      suppressed by intermittent magnetic field exposures compared to that in sham
      controls. Thus, several magnetic field exposure paradigms failed to alter the
      rising phase of the melatonin rhythm in pineal gland content or in circulation.
      These findings indicate that the biological clock mechanism that mediates
      photoperiodic time measurement in this seasonally breeding rodent is resistant to
      a variety of acute continuous or intermittent magnetic field exposures.

PMID- 9247204
TI  - The validity of melatonin as an oncostatic agent.
AB  - The validity of melatonin as a prominent, naturally occurring oncostatic agent is
      examined in terms of its putative oncostatic mechanism of action, the correlation
      between melatonin levels and neoplastic activity, and the outcome of
      therapeutically administered melatonin in clinical trials. Melatonin's mechanism
      of action is summarized in a brief analysis of its actions at the cellular level,
      its antioxidative functions, and its indirect immunostimulatory effects. The
      difficulties of interpreting melatonin levels as a diagnostic or prognostic aid
      in cancer is illustrated by referral to breast cancer, the most frequently
      studied neoplasm in trials regarding melatonin. Trials in which melatonin was
      used therapeutically are reviewed, i.e., early studies using melatonin alone,
      trials of melatonin in combination with interleukin-2, and controlled studies
      comparing routine therapy to therapy in combination with melatonin. A table
      compiling the studies in which melatonin was used in the treatment of cancer in
      humans is presented according to the type of neoplasm. Melatonin's suitability in
      combination chemotherapy, where it augments the anticancer effect of other
      chemotherapeutic drugs while decreasing some of the toxic side effects, is
      described. Based on the evidence derived from melatonin's antiproliferative,
      antioxidative, and immunostimulatory mechanisms of action, from its abnormal
      levels in cancer patients and from clinical trials in which melatonin was
      administered, it is concluded that melatonin could indeed be considered a
      physiological anticancer substance. Further well-controlled trials should,
      however, be performed in order to find the link between its observed effects and
      the underlying mechanisms of action and to define its significance as a
      therapeutic oncostatic agent.

PMID- 9247205
TI  - Melatonin inhibits oxidative modification of human low-density lipoprotein.
AB  - An important property of melatonin is that it is a free-radical scavenger or
      antioxidant. Since free radicals can induce oxidative modification of low-density
      lipoprotein (LDL), a process believed to be involved in atherogenesis, we were
      prompted to evaluate the capacity of melatonin to prevent oxidative modification
      of LDL. To induce oxidation, human LDL (0.4 mg protein/ml) was incubated at 37
      degrees C with either 10 microM cupric chloride or 10 mM 2,2'-azo-bis-(2
      amidinopropane) dihydrochloride (AAPH) for 3 hr or 24 hr, respectively. Several
      assays were then performed to unequivocally determine the extent of LDL
      oxidation. Compared to native LDL, oxidized LDL had increased agarose gel
      electrophoretic mobility and weaker immunoreactivity with a murine monoclonal
      antibody to human apolipoprotein B-100. Measurement of thiobarbituric acid
      reactive substances (TBARS) revealed that native LDL contained 1.8 +/- 0.6 nmoles
      TBARS/mg protein, whereas copper-oxidized LDL contained 53 +/- 4 nmoles TBARS/mg
      protein. However, when present during incubation, melatonin (0.125-4 mM)
      inhibited in a concentration-dependent manner the increase in electrophoretic
      mobility, decrease in immunoreactivity of LDL, and increase in formation of TBARS
      caused by either copper or AAPH. In a fourth assay, phospholipid analysis of LDL
      was performed. Native LDL contained 420 +/- 9 nmoles phosphatidylcholine (PC)/mg
      LDL protein and 30 +/- 20 nmoles lysophosphatidylcholine (LysPC)/mg LDL protein.
      LDL incubated with copper had a decreased PC content (276 +/- 48 nmoles PC/mg LDL
      protein) and increased LysPC content (76 +/- 22 nmoles LysPC/mg LDL protein). But
      when present during the incubation of LDL with copper, melatonin attenuated in a
      concentration-dependent manner the degradation of PC to LysPC. Therefore, we
      conclude that melatonin can inhibit oxidative modification of LDL in vitro.

PMID- 9247206
TI  - Effect of pinealectomy, superior cervical ganglionectomy, or melatonin treatment
      on 24-hour rhythms in ornithine decarboxylase and tyrosine hydroxylase activities
      of rat spleen.
AB  - Diurnal variations in splenic ornithine decarboxylase and tyrosine hydroxylase
      activities were examined in rats subjected to pinealectomy, bilateral superior
      cervical ganglionectomy, or their respective sham operations. Rats were treated
      with Freund's complete adjuvant or its vehicle 2 days before sacrifice. After
      immunization, splenic ornithine decarboxylase activity was augmented 5-6-fold. In
      both immunized and nonimmunized sham-operated rats, significant diurnal
      variations in ornithine decarboxylase activity were detectable, with a maximum at
      early morning, acrophases after Cosinor analysis varying from 0845 to 1048h. In
      pinealectomized or superior cervical ganglionectomized, immunized rats, ornithine
      decarboxylase activity attained values 22-27% lower than those of immunized sham
      operated controls, while amplitude decreased significantly by 27-30%.
      Administration of melatonin (30 microg/animal s.c. at late evening for 11 days in
      immunized rats) significantly augmented mesor levels of splenic ornithine
      decarboxylase activity and increased the amplitude of the diurnal rhythm both in
      pinealectomized and in superior cervical ganglionectomized rats. Melatonin
      treatment also augmented rhythm mesor in immunized, sham-ganglionectomized rats,
      as well as rhythm amplitude in immunized and nonimmunized, sham-ganglionectomized
      rats. Splenic tyrosine hydroxylase activity attained its maximum at late
      afternoon and early night, with acrophases varying from 1800 to 2023h.
      Immunization significantly increased mesor values of splenic tyrosine hydroxylase
      activity, whereas neither pinealectomy nor superior cervical ganglionectomy
      affected circadian rhythm parameters. Melatonin treatment augmented mesor values
      of tyrosine hydroxylase rhythm and increased its amplitude in pinealectomized,
      ganglionectomized, or sham-operated rats. The results are compatible with the
      view that the pineal gland plays a role in circadian changes of immune
      responsiveness in rat spleen via an immunopotentiating effect of melatonin on
      splenic cell proliferation.

PMID- 9247207
TI  - Melatonin-sensitive, serum-stimulated signalling in ovine pars tuberalis.
AB  - In primary cultures of ovine pars tuberalis (oPT), serum acts through melatonin
      sensitive mechanisms independent of cyclic AMP to increase the phosphorylation of
      the Ca2+/cyclic AMP response element binding protein (CREB). Immunocytochemical
      and biochemical assays were used to characterize the active components of serum
      and the signalling pathways through which they and melatonin function in oPT. The
      stimulatory effect of serum was heat-labile, sensitive to precipitation by
      methanol, and required components with a mass greater than 10 KDa implicating
      peptide or protein factors as the active agent. Serum increased the cytosolic
      free Ca2+ concentration ([Ca2+]i) of oPT cells. Serum also enhanced the release
      of [3H]-choline and [3H]-arachidonic acid from prelabeled cells, demonstrating
      that factors present in serum increase the breakdown of cellular phospholipids.
      This effect, however, was not blocked by melatonin (1 microM). Serum also caused
      a dose-dependent increase in levels of immediate early gene immunoreactivity,
      confirming that factors in serum have the ability to control transcription in the
      oPT. Down-regulation of protein kinase C (PKC) by treatment with 12-0
      tetradecanoylphorbol-13-acetate (TPA, 100 nM) or treatment with a specific PKC
      inhibitor (RO-31-8220, 1 microM), did not affect protein kinase A-mediated
      stimulation of CREB phosphorylation. However, down-regulation of PKC blocked the
      acute stimulatory effects of TPA (100 nM) and of serum (1%). Moreover, RO-31-8220
      abolished the stimulatory effect of TPA (100 nM) and strongly attenuated that of
      serum (1%). These results demonstrate that serum increases the phosphorylation of
      CREB by stimulating cyclic AMP-independent, PKC-dependent, signalling pathways
      within the oPT. PKC may be activated through increased phospholipid catabolism
      and/or raised [Ca2+]i.

PMID- 9247209
TI  - Stephen L. Gans Visiting Guest Lecture: central venous catheters for parenteral
      nutrition: a double-edged sword.

PMID- 9247208
TI  - Melatonin suppresses vasospastic effect of hydrogen peroxide in human umbilical
      artery: relation to calcium influx.
AB  - We evaluated the hydroxyl radical scavenging effect of melatonin on the
      vasospastic action induced by hydrogen peroxide in human umbilical artery.
      Helical sections were made of umbilical arteries obtained from healthy pregnant
      women who were delivered between 37 and 39 weeks of gestation. Changes in maximal
      potassium chloride (KCl, 10[-2] M)-induced tension were measured in umbilical
      artery segments with intact endothelium. Segments were treated with H(2)O(2) (10[
      9] M to 10[-7] M) only, or were pretreated with an H(2)O(2) scavenger (catalase,
      2,000 IU), a hydroxyl radical scavenger (mannitol, 10[-2] M), or melatonin (10[
      8] M to 10[-6] M). The effect of H(2)O(2) on the response of the segments of
      umbilical artery to external calcium was determined. Changes in KCl-induced
      contraction were also determined in segments pretreated with an inhibition of
      intracellular calcium release (ryanodine, 10[-4] M) prior to exposure to
      H(2)O(2). Pretreating the segments of umbilical arteries with H(2)O(2) (10[-8] M,
      10[-7] M) significantly potentiated the maximal contraction induced by KCl (P <
      0.0001, P < 0.03, respectively). Pretreatment with either catalase or mannitol
      significantly reduced the vasospastic effect of H(2)O(2) (10[-8] M) (P < 0.0001,
      P < 0.0001, respectively). Melatonin also significantly reduced the vasospastic
      effect of H(2)O(2) (10[-8] M), in a concentration-dependent manner (P < 0.0001).
      H(2)O(2) (10[-8] M) significantly increased the contractile response to external
      calcium. Melatonin pretreatment significantly suppressed the contractile response
      to external calcium. Treatment with ryanodine prior to exposure to H(2)O(2) did
      not affect KCl-induced contraction. Results suggest that H(2)O(2) potentiates the
      KCl-induced maximal contraction of the human umbilical artery, perhaps by
      increasing calcium influx via activation of the voltage-dependent calcium
      channel. Melatonin significantly suppresses the vasospastic effect of H(2)O(2),
      probably due to its scavenging of the hydroxyl radical.

PMID- 9247211
TI  - Cardiac arrest before repair or extracorporeal membrane oxygenation cannulation
      does not increase the mortality rate associated with congenital diaphragmatic
      hernia.
AB  - Despite recent advances in the management of high-risk congenital diaphragmatic
      hernia (CDH), mortality remains high. Deaths occur later because infants with
      inadequate pulmonary parenchyma are treated aggressively but eventually succumb
      to respiratory failure. In an attempt to identify absolute predictors of
      mortality the authors examined retrospectively their experience with CDH to
      determine if cardiac arrest before repair or initiation of extracorporeal
      membrane oxygenation (ECMO) invariably increased mortality. The authors reviewed
      the charts of 119 infants who had high-risk CDH treated between 1981 and 1994.
      They were divided into two groups: those that suffered cardiopulmonary arrest
      (CA, n = 21) before CDH repair or ECMO cannulation; and those that did not (NCA,
      N = 98). The authors compared mortality rate, ventilatory parameters, duration
      of, and complications on ECMO, as well as length of hospitalization between
      groups. Twenty-one infants suffered CA before initiation of ECMO support or CDH
      repair. Three infants (14%) suffered CA before arrival at our institution; seven
      (33%) after, and 11 (53%) both before and after arrival. There was no difference
      between the CA and NCA groups in terms of birth weight, gestational age, race and
      gender mix, or pregnancy and delivery complications. Five-minute Apgar scores
      were significantly lower in the CA group compared with the NCA group (4.6 v 5.7,
      P = .04). The CA group also had significantly worse "best postductal" blood gas
      and ventilatory parameters. There was no significant difference in length of
      hospitalization, time from admission to ECMO cannulation or CDH repair, or
      incidence of complications while on ECMO between the two groups. CA cases were
      more likely to require ECMO support (76% v 48%, P = .02) and to stay on ECMO for
      a more prolonged period than NCA cases (5.8 v 3.8 days, P = NS). However, there
      was no significant difference in overall survival between CA and NCA cases (43% v
      51%, P = NS). Cardiopulmonary arrest before repair of CDH or ECMO cannulation is
      not a univariate independent predictor of mortality and therefore should not
      preclude these high-risk infants from maximum intensive care therapy, including
      ECMO cannulation.

PMID- 9247210
TI  - Firearm injury among urban youth during the last decade: an escalation in
      violence.
AB  - PURPOSE: To better characterize firearm violence in urban youth, the authors
      investigated the circumstances and outcome of shootings among youths under 17
      years of age. METHODS: A retrospective case review was undertaken of all patients
      under 17 years of age treated for a gunshot wound at two adjoining level I Trauma
      Centers (adult and pediatric) administering to a predominantly lower
      socioeconomic population from January 1986 to December 1995. Demographics, injury
      severity, circumstances, and outcome of injury were analyzed. RESULTS: 323 youths
      were wounded by firearms. The mean age was 12.8 years, and 82.3% were boys. There
      was a 110% increase in frequency of wounding noted during the second half of
      study (219 v 104), predominantly in the adolescent subset (160% increase for age
      greater than 12 years v 30% increase for age 12 years and under). The mean injury
      severity score and trauma score were 9.3 and 14.4, respectively. Violent
      circumstances (assault, crossfire, drive-by shooting, suicide) accounted for
      60.4% of injuries and more than doubled over the study period (26.7% of total in
      the first 2 years [n = 4], 68.8% in the last 2 years [n = 55]). Unintentional
      injuries (self nonsuicide, family, friend) accounted for 26.3% of the injuries
      and declined in relative frequency over the study period (46.7% of total in the
      first 2 years [n = 7], 20.0% in the last 2 years [n = 16]). Black boys had the
      highest wounding incidence (9.2/1,000 population), were most commonly injured by
      assault (29.0%), and had a higher mean number of wounds (1.8). White boys had a
      lower wounding incidence (3.1/1,000 population), were more often injured
      unintentionally by a friend (41.2%), and had a lower mean number of wounds (1.3),
      none as a result of violence. Girls had a wounding incidence of less than 2/1,000
      and were most commonly injured in crossfire (40.7%). Ten percent of shootings
      were fatal. The assailant was known to the victim in 52.8% of children less than
      6 years of age, but only 24.7% of children over 12 years of age. CONCLUSIONS: The
      incidence of gunshot wounds in the youth of this urban population has increased
      substantially over the past decade. Adolescent black boys were the most frequent
      victims of these shootings. There has been a disproportionate growth in violent
      circumstances surrounding the shootings.

PMID- 9247212
TI  - Stable isotopic quantitation of protein metabolism and energy expenditure in
      neonates on- and post-extracorporeal life support.
AB  - It is generally assumed that extracorporeal life support (ECLS) provides a
      metabolic "rest state" by replacing approximately 80% of cardiopulmonary work.
      The aim of this study was to precisely quantify neonatal energy expenditure (EE)
      and whole-body protein metabolism on (during) and post (after) venoarterial ECLS
      using stable isotope tracer techniques. Nine parenterally fed neonates on-ECLS
      were studied at 7.8 +/- 1.0 days of life (mean +/- SE), five of which were
      studied post-ECLS on 27.0 +/- 5.4 days of life. EE and whole-body protein
      metabolism were quantified using a primed, continuous infusion of L-[1
      (13)C]leucine and NaH13CO3. The neonates studied on- and post-ECLS had similar
      rates of endogenous leucine flux (370 +/- 46 micromol/kg/h v 339 +/- 76
      micromol/kg/h), leucine oxidation (161 +/- 22 micromol/kg/h v 121 +/- 25
      micromol/kg/h), nonoxidative disposal rates of leucine (313 +/- 37 micromol/kg/h
      v 331 +/- 75 micromol/kg/h), net protein balance (-2.31 +/- 0.8 g/kg/d v -0.33 +/
      1.1 g/kg/d), and EE (88.6 +/- 7.7 kcal/kg/d v 84.3 +/- 9.2 kcal/kg/d). These
      results demonstrate that neonates on-ECLS are in hypermetabolic and protein
      catabolic states that continue in the post-ECLS phase. The authors conclude that
      ECLS does not provide a metabolic "rest state."

PMID- 9247213
TI  - Fetoscopic gene therapy for congenital lung disease.
AB  - Fetal gene therapy offers the promise of cure for certain genetic diseases, like
      cystic fibrosis and surfactant protein B deficiency. The authors hypothesized
      that a fetoscopic approach could attain a high level of organ-specific gene
      transfer to the fetal lung late in gestation. To test this hypothesis the authors
      examined the efficacy, specificity, and toxicity of recombinant adenovirus
      mediated transfer of the beta-galactosidase marker gene to the lung of late
      gestation fetal sheep using a fetoscopic technique. Twelve fetal sheep of 125 to
      135 days' gestation (term, 145 days) underwent fetoscopic bronchoscopy and
      intratracheal administration of a replication-deficient adenoviral vector that
      transduces the beta-galactosidase marker gene. Escape of administered virus was
      prevented by the fetoscopic deployment of a detachable silicone balloon in the
      fetal trachea. All fetuses survived until being killed at 2 days after vector
      delivery for the histopathologic assessment of vector efficacy and specificity.
      Optimal beta-galactosidase transgene expression was observed at a viral titer of
      2 x 10(12) particles per milliliter of administered volume. Expression was
      greatest in the distal pulmonary parenchyma, particularly in type II pneumocytes,
      and extended out to the pleura. There was no evidence of gene transfer in either
      the large conducting airways or in any other fetal organ. The authors have
      developed a minimally invasive technique for the specific pulmonary delivery of
      gene therapy vectors to the fetus with no associated acute toxicity. Gene
      transfer to the late gestation fetus for the treatment of congenital pulmonary
      disease may be feasible through fetoscopy.

PMID- 9247214
TI  - Fetendo-clip: a fetal endoscopic tracheal clip procedure in a human fetus.
AB  - Fetal tracheal occlusion accelerates lung growth and corrects the often fatal
      pulmonary hypoplasia seen in fetuses with congenital diaphragmatic hernia.
      Fetoscopy presents a unique opportunity to glimpse into the world of the fetus,
      but its use, until recently, has been limited to diagnostic and simple
      procedures. Using fetoscopic techniques ("Fetendo"), we now report successful
      tracheal occlusion in a 30-week-old fetus for the treatment of congenital
      diaphragmatic hernia.

PMID- 9247215
TI  - Steroid withdrawal in tacrolimus (FK506)-treated pediatric liver transplant
      recipients.
AB  - PURPOSE: The use of steroids in pediatric transplant recipients is associated
      with significant adverse side effects. The authors examined the feasibility of
      steroid withdrawal in patients who underwent immunosuppression with tacrolimus
      (FK506; FK). METHODS: All pediatric liver transplant recipients on FK greater
      than 6 months were evaluated for steroid withdrawal. FK was administered 0.3
      mg/kg/d in two divided doses. Steroids were tapered as tolerated with goals of
      0.2 to 0.3 mg/kg/d at 6 weeks, 0.2 to 0.3 mg/kg every other day at 3 months, and
      complete withdrawal after 6 months. Steroid bolus and taper were instituted for
      enzyme elevation or rejection during biopsy. RESULTS: Twenty-nine patients
      underwent evaluation for steroid withdrawal. Five patients could not be placed on
      FK506 monotherapy (chronic, recurrent rejection or LPD). The remaining 24 had
      steroids withdrawn. Tweleve (50%) had no sequelae and continue on FK monotherapy
      (mean, 22 months off steroids). The other 12 required intermittent steroid
      therapy for presumed or biopsy-proven rejection (n = 7), graft dysfunction (FK
      toxicity, n = 2), lymphoproliferative disease necessitating reduction in FK (n =
      2) or exacerbations of asthma (n = 1). Five of these 12 patients are now on FK
      monotherapy (mean, 6 months) for a total of 17 of the 24 (71%) currently off
      steroids. CONCLUSION: FK monotherapy can be successfully used to withdraw steroid
      therapy in the majority of pediatric liver transplant recipients with few
      sequelae.

PMID- 9247216
TI  - In utero hematopoietic stem cell transplants prolong survival of postnatal kidney
      transplantation in monkeys.
AB  - The authors hypothesized that in utero transplantation of T-cell-depleted
      paternal marrow into rhesus monkey fetuses would induce tolerance to postnatal
      kidney grafts from the marrow donor. T-cell-depleted paternal bone marrow was
      transplanted intraperitoneally into two female fetal rhesus monkeys at 61 +/- 1
      days' gestation. Chimeric monkeys (n = 2) received kidney transplants from
      paternal donors. Control monkeys (n = 2) underwent kidney transplants without
      prior in utero stem cell transplants. Both chimeric monkeys demonstrated low
      level (<0.1% donor cells) engraftment in the bone marrow and peripheral blood
      using the polymerase chain reaction assay for the Y chromosome. The mixed
      lymphocyte reaction demonstrated hyporeactivity to the donor. Control animals
      demonstrated severe acute rejection and graft failure 1 week posttransplant. The
      first chimeric monkey had no significant clinical or sonographic evidence of
      renal failure until 7 weeks after the transplant. Biopsy findings showed mild
      rejection 1 week postoperatively, but rejection did not significantly progress
      until 5 weeks later. The second chimeric monkey had no significant clinical or
      sonographic changes for 4 weeks, but evidence of moderate rejection was seen on
      biopsy results. This monkey was given a 10-week course of immunosuppression, and
      had no clinical or sonographic renal deterioration, although biopsy results
      showed chronic rejection that was confirmed when electively euthanized 8 months
      later. Our data suggest that in utero transplantation of hematopoietic stem cells
      can increase the survival of a kidney allograft in the rhesus monkey.

PMID- 9247217
TI  - Is nasogastric tube decompression necessary after major abdominal surgery in
      children?
AB  - Nasogastric (NG) decompression has traditionally been used after major abdominal
      surgery in pediatric patients. This study was designed to determine if NG tubes
      could be routinely omitted in pediatric patients undergoing major abdominal
      procedures. Between January 1993 and December 1995, 83 patients had follow-up
      prospectively without NG decompression after a variety of major abdominal
      surgeries. NG tubes were inserted for persistent vomiting or abdominal
      distension. Exclusion criteria included bowel obstruction, intestinal atresia,
      and perforation of the stomach or duodenum. Ages ranged from 13 days to 22 years.
      Seventy-four patients (89%) were treated successfully without postoperative NG
      decompression. There were no cases of pneumonia, wound dehiscence, anastomotic
      leak, or delay in return of gastrointestinal function. Nine patients required NG
      tubes for persistent vomiting or abdominal distension. An anastomotic leak
      developed in one patient after endorectal pull-through. NG decompression is
      unnecessary after most major abdominal operations in pediatric patients. The
      endorectal pull-through may represent a group of patients that benefit from
      routine decompression.

PMID- 9247218
TI  - Cystic lung lesions with systemic arterial blood supply: a hybrid of congenital
      cystic adenomatoid malformation and bronchopulmonary sequestration.
AB  - Congenital cystic adenomatoid malformation and bronchopulmonary sequestration are
      congenital lung tumors that are classically described as having distinct
      embryology, pathology, and natural history. The authors treated six patients who
      had prenatally diagnosed lung masses that displayed clinicopathologic features of
      both lesion types. At prenatal diagnosis (19 to 30 weeks' gestation), all six
      lesions were classified sonographically as congenital cystic adenomatoid
      malformation, and none of the masses appeared to have a systemic arterial blood
      supply as seen by color flow Doppler study. Two of the six masses showed size
      regression antenatally. At the time of surgery, all six lesions had a systemic
      vessel directly from the aorta--five cases were consistent grossly with an
      intralobular bronchopulmonary sequestration, and one case was consistent with an
      extralobular bronchopulmonary sequestration. However, all six lesions displayed
      congenital cystic adenomatoid malformation histology. Hydrops developed in one
      fetus with a huge mass, and that fetus underwent successful fetal surgical
      resection (left lower lobectomy) at 22 weeks' gestation with delivery at 35
      weeks' gestation. One neonate with a large extralobular bronchopulmonary
      sequestration was treated with resection and extracorporeal membrane oxygenation
      (ECMO) but died of pulmonary hypoplasia. Four other patients who had much smaller
      masses underwent elective lower lobectomy after birth. These findings emphasize
      the importance of seeking an anomalous blood supply in patients who have
      congenital lung lesions. These "hybrid" cases suggest a similar embryological
      origin for congenital cystic adenomatoid malformation and bronchopulmonary
      sequestration.

PMID- 9247219
TI  - Hepatocyte growth factor enhances intestinal mucosal cell function and mass in
      vivo.
AB  - Hepatocyte growth factor (HGF), originally known to stimulate hepatocyte DNA
      synthesis, recently has been shown to enhance growth of intestinal epithelial
      cells in vitro. However, there have been no studies on the effect of HGF on the
      function of intestinal epithelial cells in vivo. This study was designed to
      examine the effect of systemically administrated HGF on intestinal epithelial
      cell mass and function. Twenty young adult male Sprague-Dawley rats underwent
      placement of jugular venous catheters connected to subcutaneously placed osmotic
      minipumps. The rats were divided into four groups based on the contents in the
      osmotic pump: Group 1 (control, n = 5), normal saline; Group 2 (n = 5), HGF 75
      microg/kg/d; Group 3 (n = 5), HGF 150 microg/kg/d; and Group 4 (n = 5), HGF 300
      microg/kg/d. After a 14 day infusion, [C14] galactose and [C14] glycine
      absorption were measured in a 10-cm segment of mid small intestine using an in
      vivo closed-recirculation technique. Mucosal DNA content and protein content of
      the same small bowel segment were determined for each group. With all three
      doses, HGF significantly increased DNA content (P < .01) and protein content (P <
      .05). HGF also significantly increased galactose absorption (P < .01) with all
      three doses. Glycine absorption was increased with a dose of 75 (P < .05) and 150
      microg/kg/d (P < .01), but not at a dose of 300 microg/kg/d. These data
      demonstrate that HGF can increase intestinal epithelial cell mass and function in
      vivo. HGF may be clinically useful in patients with short bowel syndrome.

PMID- 9247220
TI  - Hepatic resection enhances growth of residual intrahepatic and subcutaneous
      hepatoma, which is inhibited by octreotide.
AB  - OBJECTIVE: The aim of this study was to evaluate whether partial hepatectomy (PH)
      enhances the growth of implanted intrahepatic and subcutaneous tumor and whether
      octreotide (OCT) can alter tumor growth. METHODS: Ninety-one ACI rats (125 g)
      underwent a laparotomy; 51 had a 66% PH and 40 were controls. Morris hepatoma
      3924A was implanted in the liver (IH) of 29 PH and 26 controls and subcutaneously
      (SC) in 22 PH and 14 control rats. OCT, 50 mg/kg, was administered
      intraperitoneally twice a day to 23 PH rats with IH (n = 15) or SC (n = 8) tumor
      implants. The remaining PH rats received a similar volume of saline (NS). PH and
      control animals were evaluated for tumor volume, metastases, and tumor and liver
      weight at 7 and 15 days. RESULTS: Group I (PH + IH + NS) showed a sixfold
      increase in IH tumor volume and 100% increase in metastases versus group II
      (controls + IH + NS) at 15 days postimplant (P < .01). Group III (PH + SC + NS)
      had a fourfold increase in SC tumor volume at 7 and 15 days versus group IV
      (control + SC + NS, P < .02). Group V (PH + IH + OCT) showed a tenfold reduction
      of IH tumor volume (P < .01) and 20% decrease in liver weight (P < .03) when
      compared with group I at 15 days. Group VI (PH + SC + OCT) similarly showed a
      threefold reduction of SC tumor volume (P < .01) and 20% decrease in tumor weight
      (P < .05) versus group III. CONCLUSION: Growth of IH and SC hepatoma is enhanced
      after PH and inhibited by OCT. This suggests that factors influencing hepatic
      replication also affect local and remote tumor growth. OCT action may be related
      to the presence of somatostatin receptors or caused by a direct antiproliferative
      effect.

PMID- 9247221
TI  - Improved long-term survival with preoperative chemotherapy for hepatoblastoma.
AB  - In 1986, The Hospital for Sick Children (Toronto, Canada) began to use a standard
      preoperative chemotherapeutic regimen for patients who had unresectable
      hepatoblastoma. In 1988, we extended this protocol to all children who had
      hepatoblastoma. Of 25 children who presented with hepatoblastoma, 22 were
      eligible for protocol therapy. After percutaneous biopsy, cycles of cisplatin (20
      mg/m2/d for 5 days) and Adriamycin (25 mg/m2/d for 3 days) were administered
      every 3 weeks by continuous intravenous infusion. A CAT scan was performed after
      the third cycle. Surgery was undertaken if response indicated that complete
      resection was possible. If not, a further one to three cycles were given until
      response was adequate. Postoperatively, therapy was continued for a total of six
      cycles. Twenty of twenty-two (91%) tumors responded to chemotherapy. Over half
      required only three cycles. Twenty hepatic resections (6 segmentectomies, 10
      lobectomies, 4 trisegmentectomies) were performed. Preoperative therapy
      significantly reduced the extent of resection calculated to be necessary for
      complete excision at an initial diagnosis of the primary tumor in all but one. In
      the two children with inadequate response, total hepatectomy and transplant was
      necessary for complete resection. No deaths or operative delays were attributed
      to chemotherapy toxicity. Nineteen of 22 children (87%) are alive with no
      evidence of disease, including both transplant patients. One death was caused by
      intraoperative bleeding and the other two were caused by metastatic lung disease
      at 22 and 26 months, respectively. Twelve children, eight with tumors that would
      have been unresectable before effective chemotherapy, have had follow-up for more
      than 5 years. This protocol of preoperative chemotherapy appears to be safe and
      effective for most children who have hepatoblastoma.

PMID- 9247222
TI  - Alimentary tract malignancies in children.
AB  - Alimentary tract malignancies in children are unusual. From 1952 to 1996, 54
      patients (55 cases) underwent surgery at The Children's Hospital, Columbus for
      intestinal malignancy. Their records were reviewed retrospectively. The mean age
      at diagnosis was 9.3 years (range, 1 to 17 years). There were 35 boys and 19
      girls (M:F ratio, 1:8). Mean follow-up was 108 months. Laparotomy was performed
      in all but one child. The primary tumor sites included the colon (31 cases),
      small bowel (12 cases), appendix (9 cases), and stomach (3 cases). Seventy-five
      percent of the tumors were non-Hodgkin's lymphomas (41 cases), followed by
      appendiceal carcinoid (9 cases), colon adenocarcinoma (3 cases), and gastric
      sarcoma (2 cases). Lymphoma occurred in 28 of 31 nonappendiceal large bowel
      tumors and was the only tumor type seen in the small intestine. There were 21
      Burkitt's, 11 lymphoblastic, 6 small cell, and 5 large cell lymphomas. There was
      a statistically significant increase in the frequency of small bowel lymphoma
      after 1982 (10 of 20) in comparison with that before 1982 (2 of 21), P < .05.
      This coincided with an increase in Burkitt's lymphoma from 5 of 21 (pre-1982) to
      16 of 20 (post-1982), and a decrease in lymphoblastic lymphomas from 7 of 21 (pre
      1982) to 2 of 20 (post-1982), P < .05. Localized disease and complete resection
      favored survival in lymphoma, whereas age, sex, and urgency of operation had no
      influence on survival. This study highlights the predominance of lymphoma as the
      most common small and large bowel tumor and highlights the emergence of
      nonendemic Burkitt's as a major entity in pediatric intestinal malignancy.

PMID- 9247223
TI  - Quantification of P-selectin expression after renal ischemia and reperfusion.
AB  - Neutrophils are important in ischemia and reperfusion injury. Multiple factors
      may be responsible for the adhesion of granulocytes to endothelial cells. P
      selectin is a carbohydrate-binding glycoprotein that is stored preformed in
      endothelial cells as Weibel-Palade bodies. This preformation implies a very early
      role of P-selectin in the leukocyte adhesion process. Previous studies of P
      selectin have not quantified its expression. The purpose of this study is to
      quantitate the expression and time course of P-selectin in response to renal
      ischemia and reperfusion injury. P-selectin was measured in 34 C57BL-6 mice after
      30 minutes of occlusive left renal ischemia followed by 20 minutes, 2, 5, 10, and
      24 hours of reperfusion. This was also performed in control and sham laparotomy
      groups. P-selectin was quantified using a new double radiolabeled 125I/131I
      monoclonal antibody technique and reported as percent injected dose per gram of
      tissue. P-selectin expression peaked at 20 minutes, plateaued up to 5 hours, and
      fell at 10 hours. Additionally, genetically altered mice that do not express P
      selectin showed no up regulation after 5 hours of reperfusion. Pathology results
      confirmed significant renal injury. Renal ischemia and reperfusion injury caused
      significant upregulation of P-selectin. Expression of P-selectin at the short
      reperfusion time of 20 minutes reinforces the premise that P-selectin is one of
      the earliest adhesion molecules expressed. This early peak is probably caused by
      the release of preformed P-selectin. The delineation of these mechanisms of
      injury may be important in understanding and preventing renal injury in
      transplantation, sepsis, and shock.

PMID- 9247224
TI  - The protective role of gastric acidity in neonatal bacterial translocation.
AB  - The acid environment of the stomach serves as an important defense against
      intestinal colonization by potentially pathogenic bacteria. The purpose of this
      study was to examine the effect of increased gastric pH on bacterial
      translocation in a neonatal rabbit model. Fifty-nine rabbit pups were delivered
      by cesarean section and randomly divided into normal acid (NA) and reduced acid
      (RA) groups. All were gavage fed and challenged with Enterobacter cloacae, 1 x
      10(6) CFU/mL. The RA group received ranitidine, 20 mg/kg/d with all feeds.
      Gastric pH was measured by pH probe before and 4 hours after bacterial challenge.
      Mesenteric lymph node (MLN), spleen, liver, midjejunum, and cecum were harvested
      for culture at 72 hours. Gastric pH in the RA group was significantly increased
      before and 4 hours after the bacterial challenge. The incidence of bacterial
      translocation to the MLN, spleen, and liver was significantly higher in the RA
      group. Log cecal and jejunal colony counts were significantly increased in the RA
      animals. The authors conclude that the gastric acidity is protective against
      intestinal colonization and translocation of potentially pathogenic bacteria in
      this neonatal rabbit model.

PMID- 9247225
TI  - Myofibroblast persistence in fetal sheep wounds is associated with scar
      formation.
AB  - The scarless repair capabilities of the fetus are influenced by the size of the
      wound and the gestational age of the fetus. Whereas small wounds heal scarlessly,
      large wounds in the same fetus heal with scar. Myofibroblasts are specialized
      fibroblasts that express alpha-smooth muscle actin (alpha-SMA), a contractile
      cytoskeletal protein. The authors hypothesized that small fetal wounds that heal
      scarlessly will have a relative absence of myofibroblasts, whereas large wounds
      that heal with scar will have abundant myofibroblasts. In this study, an
      incisional wound and four punch biopsy wounds of 2, 4, 6, and 10 mm diameter were
      placed on the backs of 60- to 90-day-gestation fetal sheep (term, 145 days).
      Fourteen days after wounding, the healed fetal wounds were harvested, the repair
      morphology was determined (scarless, transitional repair, or scar), and the
      expression of alpha-SMA was analyzed by immunohistochemistry. In the second part
      of this study the authors analyzed the temporal expression of alpha-SMA in fetal
      wounds at 1, 2, 3, and 7 days after wounding in 70-day-gestation fetal sheep. In
      the 14-day wounds, the authors found that alpha-SMA was not expressed in any
      incisional or 2-mm wound that healed scarlessly, but it was expressed in all
      wounds that healed with scar. Overall, alpha-SMA expression strongly correlated
      with increasing wound size (P < .005). Myofibroblasts were seen as early as 24
      hours after wounding, and at 3 and 7 days all wounds showed strong expression of
      alpha-SMA. These results demonstrate that although myofibroblasts are induced
      early in fetal wound repair, by 14 days there is a notable lack of myofibroblasts
      in wounds that heal scarlessly and an abundance of myofibroblasts in those wounds
      that scar. By determining the factors that regulate the disappearance of the
      myofibroblast in scarless fetal wounds, the authors hope to gain new insights
      into the mechanisms of scarless fetal repair.

PMID- 9247226
TI  - Transforming growth factor beta-1 decreases interstitial collagenase in healing
      human fetal skin.
AB  - Fetal dermal wounds heal without scarring. Because wound repair requires
      extracellular matrix turnover, the authors hypothesized that fetal skin would
      have increased levels of proteinases responsible for matrix degradation compared
      with adult skin. It was further hypothesized that transforming growth factor beta
      1 (TGF-beta1) induces scarring in fetal skin by altering proteinase synthesis. A
      model of human fetal skin transplanted subcutaneously onto immunodeficient mice
      was used to study the role of matrix metalloproteinases in healing human fetal
      skin. In this model, transplanted second trimester fetal skin heals without
      scarring; addition of TGF-beta1 induces scarring. Proteinases were detected by
      immunohistochemistry in untransplanted fetal skin, untransplanted adult skin, TGF
      beta1-treated fetal skin grafts, and sucrose-treated control grafts. In
      untransplanted fetal skin, interstitial collagenase, stromelysin-1, and
      gelatinase A were found in dermal cells and keratinocytes, and around vascular
      structures. Proteinases were detected in adult skin at similar locations but
      stained less intensely. Addition of TGF-beta1 decreased interstitial collagenase
      in fetal skin, but detection of gelatinase A and stromelysin-1 was unchanged. The
      authors conclude that matrix metalloproteinases are present in midgestation human
      fetal skin and that more proteinase-containing cells are found in fetal skin than
      in adult skin. Manipulation of fetal skin with TGF-beta1 is accompanied by a
      decrease in interstitial collagenase. These data suggest that the increased
      matrix metalloproteinases found in fetal skin contribute to scarless healing and
      that the fibrotic effects of TGF-beta1 on fetal skin may be mediated in part by
      decreasing the synthesis of interstitial collagenase.

PMID- 9247227
TI  - Single-stage repair of Hirschsprung's disease: a comparison of 109 patients over
      5 years.
AB  - Current management of Hirschsprung's disease (HD) typically involves staged
      therapy, which necessitates multiple hospital admissions and associated costs.
      The authors therefore investigated the course and outcome of treating such
      children using a single-staged (SS) approach, and compared them with those
      treated via multiple-staged (MS) therapy. The cases of one hundred nine
      consecutive patients who presented with HD from 1991 to 1996 were reviewed. Four
      patients were excluded (two unrelated deaths, two with small intestinal
      aganglionosis). Twenty-one of the remaining 105 patients underwent SS repair.
      Both groups were similar in gender, age at diagnosis, and frequency of
      comorbidities. Repair was possible in 100% of the SS patients. Complications,
      including enterocolitis, occurred in 63% of patients, and did not significantly
      differ between groups. The outcome in SS patients was unaffected by whether the
      repair was performed before or after 30 days of life. The outcome was unaffected
      by operative weight in either group. By contrast, the number of hospital
      admissions and total length of stay was significantly higher in the MS group,
      which resulted in a twofold increase in total costs associated with MS repair
      compared with SS repair. These data indicate that primary repair of HD is
      efficacious (even in the newborn), with morbidity equal to MS repair, and
      requires fewer hospital admissions. The significant savings to the patient and
      the health care system suggest that SS repair may be an improved strategy for
      treating HD.

PMID- 9247228
TI  - Differential collagen I gene expression in fetal fibroblasts.
AB  - PURPOSE: Fetal wound healing is characterized by the regeneration of normal
      dermis and the absence of scar. Transforming growth factor beta-1 (TGF-beta1) is
      a ubiquitous cytokine with potent fibrogenic effects in both postnatal and fetal
      wounds. Supplementing fetal wounds with TGF-beta1 results in increased fibrosis
      consisting primarily of collagen I. We hypothesized that the lack of scar
      formation in fetal wounds may be caused by differential collagen I gene (COL1A1)
      expression. The authors examined basal collagen Ia gene expression in human
      fetal, newborn, and adult dermal fibroblasts after stimulation with exogenous TGF
      beta1. METHODS: Subconfluent human dermal fibroblasts from fetal, newborn, and
      adult cell lines were incubated for 24 hours, then stimulated by incubation for 4
      hours with 1 ng/mL of human recombinant TGF-beta1, or with media alone for basal
      collagen gene expression, and then placed in guanidium isothyocyanate buffer. To
      quantitate COL1A1 gene expression, total cellular RNA was extracted and subjected
      to northern and slot blot hybridization analysis with Dig-labeled COL1A1 probes.
      The membrane was exposed to x-ray film for 15 minutes and developed. RESULTS:
      Scant COL1A1 gene transcript was detected in control fetal fibroblasts. Brief
      stimulation with of TGF-beta1 upregulated the COL1A1 gene transcription in fetal
      fibroblasts. Gene expression for COL1A1 in both postnatal cell lines appeared
      similar in treated and untreated cells. Housekeeping control (GAPDH) confirmed no
      difference in total amount of RNA at the start or end of the experiment.
      CONCLUSION: COL1A1 gene expression is notably absent in unstimulated fetal
      fibroblasts, but is upregulated by TGF-beta1. In contrast, postnatal fibroblasts
      demonstrate significant constitutive COL1A1 gene expression at baseline and
      unchanged after TGF-beta1 stimulation. This differential regulation may
      contribute to the ability of fetal wounds to regenerate without scar and explain
      the effect of exogenous TGF-beta1 to increase fibroplasia in fetal dermal
      incisional wounds.

PMID- 9247230
TI  - Idiopathic constipation in childhood is associated with thickening of the
      internal anal sphincter.
AB  - This study was undertaken to search for a rational basis for the use of anal
      dilatation and internal sphincterotomy as the treatment for chronic intractable
      constipation in children. Sixteen children, age 5 months to 13 years, who had
      constipation resistant to conservative treatment were compared with 39 age
      matched controls. History and current symptoms were assessed using a standard
      questionnaire. Internal and external and sphincter morphology was assessed on
      clinical examination and by anal endosonography, using a 10-MHz rotating
      endoprobe to provide accurate measurement of the various components of the anal
      canal. The control group showed a linear correlation between the thickness of the
      internal anal sphincter and both age and weight, increasing from 0.4 mm in
      infancy to 0.9 mm in adolescence. Children who had constipation displayed
      significant thickening of the internal sphincter (range, 0.5 to 1.9 mm, P = .005)
      which was independent of the length of the history (P = .103). There was no
      difference in the morphology of the external anal sphincters between the groups.
      The finding of a hypertrophied internal anal sphincter could provide a rational
      basis for anal dilatation and internal sphincterotomy as treatment for idiopathic
      constipation.

PMID- 9247229
TI  - Hyaluronic acid inhibits fetal platelet function: implications in scarless
      healing.
AB  - Platelets are important for the initiation of inflammation in adults, but the
      role of fetal platelets in fetal wound healing is unclear because fetal dermal
      wounds heal with a minimal inflammatory response and lack of excessive scarring.
      Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly
      hyaluronic acid (HA), this study was designed to test the hypothesis that HA
      inhibits the reactivity of platelets and thus contributes to the minimal scarring
      characteristic of fetal tissue repair. Platelets were isolated from 10 fetal pigs
      at day 80 of gestation (term, 115 days) and exposed to 0.5 mg/mL of arachidonic
      acid, an agent shown in prior studies to evoke maximal aggregation and
      degranulation of fetal platelets. The ability of HA at 0.1 and 0.5 mg/mL to
      inhibit this response was determined. The presence of HA resulted in a dose
      dependent reduction in platelet aggregation at 180 seconds (control, 99.7 +/-
      0.3%; HA [0.1 mg/mL] 91.7 +/- 3.8%; and HA [0.5 mg/mL] 48.5 +/- 9.0%; P < .005 v
      control). The onset of aggregation was also significantly delayed by 0.5 mg/mL of
      HA (13.5 +/- 2.5 seconds) compared to control (2.9 +/- 0.7 seconds), P < .05. No
      significant diminution of platelet aggregation could be achieved by the addition
      of other GAGs at similar concentrations. HA also significantly impaired the
      release of platelet-derived growth factor (PDGF)-AB from fetal platelets. The
      authors conclude that HA, the predominant GAG in fetal dermal matrix, inhibits
      platelet aggregation and cytokine release. This inhibition of platelet
      aggregation and resultant inflammatory response may explain, in part, the minimal
      inflammation and scarless healing characteristic of fetal dermal repair.

PMID- 9247231
TI  - Gluteus maximus augmentation for the treatment of fecal incontinence.
AB  - Fecal incontinence is a devastating problem for school-aged children and adults.
      Medical and biofeedback therapies are unsuccessful in most patients who have
      severely defective internal and external sphincters. Continued fecal incontinence
      frequently leads to social isolation and withdrawal. Gluteus maximus augmentation
      of the sphincter mechanism is one surgical method for treating fecal
      incontinence. The authors present their results with gluteus maximus augmentation
      of the anal sphincter and describe patient selection criteria. From 1992 through
      1996, seven patients underwent gluteus maximus augmentation of the anal sphincter
      for fecal incontinence. Six of these patients were children 5 to 6 years of age
      who had major deficiencies of their anorectal sphincter demonstrated by
      manometry. One patient was a 56-year-old adult woman who had acquired idiopathic
      fecal incontinence. Four of the six children (67%) had imperforate anus and two
      had cloacal anomalies (33%). The augmentation was performed in three stages. A
      sigmoid-end colostomy with a Hartman's pouch was followed 1 month later by
      rotation of a portion of the gluteus maximus for anorectal sphincter
      augmentation. A colostomy take down was performed 2 to 4 months later. All
      patients underwent dilatation after sphincter augmentation and were taught muscle
      exercises for using their neosphincter during the period before colostomy take
      down. Four of six children and the adult are continent postoperatively (71%).
      Both patients who remain incontinent are unable to sense rectal distention
      clinically or on anal manometric analysis but have excellent voluntary sphincter
      tone. Fecal incontinence can be successfully treated with gluteus maximus
      augmentation in carefully selected patients. Patients unable to sense rectal
      distension are unlikely to benefit from this procedure. The presence of a rectal
      reservoir and a skin-lined anal canal also appear to be important in attaining
      fecal continence.

PMID- 9247232
TI  - Long-term stooling patterns in infants undergoing primary endorectal pull-through
      for Hirschsprung's disease.
AB  - Primary endorectal pull-through (ERPT) has become an increasingly popular method
      of caring for neonates and young infants who have Hirschsprung's disease. This
      study evaluated the long-term stooling patterns and continence rates of patients
      who had a primary ERPT as a young infant. The records of 24 infants who underwent
      a primary ERPT for Hirschsprung's disease were reviewed. The patients' families
      (those patients over 3 years of age, n = 12) underwent a detailed interview that
      graded continence from 0 (poor) to 10 (normal). Mean age at ERPT was 15 +/- 17
      days (range, 2 to 67). Mean follow-up was 1,036 +/- 614 days. Nine patients
      suffered from 20 episodes of enterocolitis. Stooling frequency declined rapidly
      in the first 6 months after the ERPT (r2 = 1.00) and more slowly after this time
      (r2 = 0.79). Continence was graded as normal (10) in one, good (6 to 9 points) in
      nine, and fair (1 to 5) in two patients, both of whom had total colonic disease.
      The authors conclude that a primary ERPT in the young infant who has
      Hirschsprung's disease can yield excellent results including normalization of
      stooling frequency and good to excellent levels of continence.

PMID- 9247233
TI  - Altered mRNA expression of the neuronal nitric oxide synthase gene in
      Hirschsprung's disease.
AB  - Nitric oxide has been described as an inhibitory neurotransmitter to mediate
      smooth muscle relaxation in the mammalian gastrointestinal tract. The enzyme
      neuronal nitric oxide synthase (NOS) catalyzes the formation of NO. The authors
      examined the expression of neuronal NOS gene at the mRNA level in intestinal
      specimens from seven patients who had Hirschsprung's disease (HD) using reverse
      transcription polymerase chain reaction (RT-PCR) technique. With 35 cycles of PCR
      reaction, substantial signals of neuronal NOS mRNA were observed in the
      ganglionic bowel in all seven patients, whereas in the aganglionic bowel,
      neuronal NOS signals were weak in three patients, and undetectable in four
      patients. By increasing the PCR cycle to 40 cycles, barely detectable signals
      were observed in two of the latter four patients. Semiquantitative analysis in
      the three patients who showed weak signals with 35 cycles of PCR indicated that
      neuronal NOS mRNA expression in aganglionic bowel was decreased at least 1/50 to
      1/100 of the level expressed in ganglionic bowel. Because absence or low level of
      expression of neuronal NOS mRNA may lead to impaired production of NO, our
      observations suggest that motility dysfunction in HD may be as a result of
      markedly decreased or no expression of the neuronal NOS gene at the mRNA level.

PMID- 9247234
TI  - Preliminary experience with intrasphincteric botulinum toxin for persistent
      constipation after pull-through for Hirschsprung's disease.
AB  - Although most children who have Hirschsprung's disease have an excellent result
      after pull-through surgery, some experience persistent constipation caused by
      "internal sphincter achalasia." Anal myectomy has been advocated for this
      problem, but it results in permanent injury to the sphincter and is not
      universally effective. Botulinum toxin has been safely used to selectively and
      reversibly weaken a variety of voluntary muscles and sphincters in both adults
      and children. Injection of botulinum toxin into the internal anal sphincter (IAS)
      should theoretically produce the same functional result as anal myectomy without
      permanent sphincter injury. Four children aged 4 to 8 years presented with
      persistent constipation after a pull-through procedure for Hirschsprung's
      disease. Two had associated encopresis, both of whom had previous myectomies. The
      authors performed four-quadrant intrasphincteric botulinum toxin injection (total
      dose, 15 U). Resting IAS pressure decreased in all children 4 to 8 weeks after
      injection. Patients have been followed up for 7 to 9 months. One child (with
      Down's syndrome) remained symptomatically unchanged. The other three families
      reported significant improvement in bowel function in their children. In two of
      these, there was a return of symptoms 6 months after injection; one child
      underwent reinjection with good results. Postinjection incontinence occurred in
      three children, but resolved after several weeks in the one who did not have
      encopresis before botulinum toxin injection. These preliminary results suggest
      that botulinum toxin may represent a less invasive alternative to anal myectomy
      for children who have severe constipation after surgery for Hirschsprung's
      disease. If myectomy is contemplated, botulinum toxin may also be useful as a
      means of predicting which children may benefit.

PMID- 9247235
TI  - Surgery for Crohn's disease in infants and children.
AB  - The course of Crohn's disease is quite variable in children. To assess the
      frequency and indications for surgery with current medical therapy, the authors
      reviewed the cases of 204 children (ages, 0.2 to 18.8 years at diagnosis, median,
      12.8 years) who had Crohn's disease treated at a single institution from December
      1968 to January 1994, with a median of 3.8 years of follow-up (range, 0.0 to 22.2
      years). Ninety-four children (46%) required surgical resection for the following
      indications: (1) failure of medical therapy with persistent symptoms or growth
      retardation (n = 44, 47%), (2) intraabdominal abscess or perforation (n = 15,
      16%), (3) fistula formation (n = 13, 14%), (4) obstruction (n = 15, 16%), (5)
      hemorrhage (n = 4, 4%), and (6) appendectomy at exploration for diagnosis (n = 3,
      3%). The probability for surgery 3 years after diagnosis is 28.8% and by 5 years
      is 47.2%. Resections included ileocolectomy (71 children), colectomy (n = 16),
      small bowel resection (n = 4), and appendectomy (n = 3). Fourteen fistulas in 13
      children required surgical intervention (7 enteroenteral, 3 enterovesical, 2
      enterovaginal, and 2 enterocutaneous). The median duration from diagnosis to
      surgery for the fistulas was 2.6 years (range 0.1 to 9.8 years). Forty patients
      experienced recurring disease after resection during follow-up with a median of
      1.8 years (range 0.4 to 18.1 years). The authors found that the course of the
      disease was unpredictable, with some children requiring early surgical
      intervention and others continuing with medical therapy for years.

PMID- 9247236
TI  - Intestinal pacemaker C-KIT+ cells and synapses in allied Hirschsprung's
      disorders.
AB  - The cause of bowel dysmotility in allied Hirschsprung's disorders (AHDs) such as
      hypoganglionosis (HYPG), immature ganglia (IMG) and neuronal intestinal dysplasia
      (NID) remains unexplained. Recent experimental studies in mice have shown that c
      kit gene product positive (C-KIT+) cells are responsible for intestinal pacemaker
      activity and that c-kit is also closely involved in synapse formation. To further
      understand the pathophysiology of AHDs, the authors used immunohistochemistry to
      study the distribution of C-KIT+ cells and synapses in the muscle layers of
      normal bowel from controls (12 cases) and bowel from patients with AHDs (10
      patients; mean age, 3.0 years; 5 HYPG, 3 NID, 2 IMG). Anti-human C-KIT serum and
      monoclonal antibody 171B5 (a novel marker of synapses) were used for
      visualization of C-KIT+ cells and 171B5+ synapses, respectively. In normal bowel
      from controls and patients with AHDs, moderate to many C-KIT immunoreactive (C
      KIT-IR+) cells were observed in the muscle layers. Myenteric plexuses were
      clearly demarcated by C-KIT-IR+ cells. 171B5 immunoreactive (171B5-IR+) synapses
      were abundant in the muscle layers and within the myenteric plexuses. In
      contrast, the number of C-KIT-IR+ cells or 171 B5-IR+ synapses was reduced in the
      muscle layers of bowel affected by AHDs, except within the myenteric plexuses,
      where there was a moderate to large number of 171B5-IR+ synapses identified. A
      lack of intestinal pacemaker C-KIT+ cells may be of great significance with
      respect to the bowel dysmotility associated with AHDs and also to the abnormal
      synapse formation seen in the muscle layers of bowel affected by these disorders.

PMID- 9247237
TI  - Prognostic classification for esophageal atresia and tracheoesophageal fistula:
      Waterston versus Montreal.
AB  - Since 1962, the Waterston classification has been used to stratify neonates who
      have esophageal atresia (EA) and/or tracheoesophageal fistula (TEF) into
      prognostic categories based on birth weight, the presence of pneumonia, and the
      identification of other congenital anomalies. In response to advances in neonatal
      care, the surgeons from the Montreal Children's Hospital proposed a new
      categorization system in 1993 in an attempt to define the current risk factors
      for patients who have EA/TEF. In the Montreal experience only two characteristics
      independently affected survival: preoperative ventilator dependence and
      associated major anomalies. The goal of this study was to determine which system
      had the greatest validity for the evaluation of prognosis in our patients with
      EA/TEF. The charts of 94 patients who had EA/TEF treated between 1972 and 1991
      were reviewed. Patients were classified using both the Waterston and Montreal
      systems. Groups were compared with Fisher's Exact test using a 95% confidence
      level for statistical significance. Eleven infants were ventilator dependent
      preoperatively; 62 children had major associated anomalies, 8 of which were
      considered life threatening. Sixteen children died within 4 years, eight during
      their initial hospital stay. Five of the eight early postoperative deaths
      occurred in the highest-risk patients (Waterston C or Montreal II). Analysis was
      performed for multiple risk factors and mortality. As in the Montreal study, the
      presence of life-threatening and major congenital anomalies represented
      significant risk factors for death. Pulmonary disease as delineated by ventilator
      dependence appeared to be more accurate than pneumonia. This study confirms the
      accuracy of the Montreal classification in defining prognosis for EA/TEF. The
      Montreal system more accurately identifies children at highest risk than the
      Waterston classification.

PMID- 9247238
TI  - Slipping rib syndrome in childhood.
AB  - Slipping rib syndrome is an unusual cause of lower chest and upper abdominal pain
      in children not mentioned in major pediatric surgical texts. The syndrome occurs
      when the medial fibrous attachments of the eighth, ninth, or tenth ribs are
      inadequate or ruptured, allowing their cartilage tip to slip superiorly and
      impinge on the intervening intercostal nerve. This may cause a variety of somatic
      and visceral complaints. Although the diagnosis may be made based on history and
      physical examination, lack of recognition of this disorder frequently leads to
      extensive diagnostic evaluations before definitive therapy. The authors report on
      four children who have this disorder.

PMID- 9247239
TI  - Esophageal replacement in children who have caustic pharyngoesophageal
      strictures.
AB  - Caustic injury to the upper aerodigestive system with scarring of the pharynx,
      hypopharynx, and esophagus is a challenging reconstructive problem. The authors
      report on seven patients who required total esophageal replacement from the
      pharynx to the stomach. Injury occurred from alkali in six and acid in one. Age
      at injury ranged from 14 months to 14 years (mean, 4.5 years.) in five boys and
      two girls. Time from injury to esophageal replacement was 6 months to 10 years
      (mean, 3.5 years). Two required pharyngeal reconstruction before and one after
      esophageal replacement. Six patients had an isoperistaltic right or transverse
      colon interposition. One who had gastric necrosis had an ileo-right colonic
      substernal interposition with creation of a jejunal reservoir. Results of barium
      swallows showed intact anastomoses in all patients. There were no leaks. Most had
      some degree of mild to moderate aspiration, and one who had left vocal cord
      paralysis had initially massive aspiration. Three patients currently eat regular
      diets; four eat but still require supplemental tube feeds. The authors conclude
      that children who have hypopharyngeal scarring and obliterated esophageal inlet
      can undergo a successful colonic esophageal replacement with high proximal
      pharyngocolic anastomosis.

PMID- 9247240
TI  - Efficacy of partial wrap fundoplication for gastroesophageal reflux after repair
      of esophageal atresia.
AB  - Gastroesophageal reflux (GER) often develops in children who have undergone prior
      repair of esophageal atresia/tracheoesophageal fistula (EA/TEF). Fundoplication
      is necessary in many of these children. The complete wrap (Nissen) fundoplication
      is often used in this setting. However, poor results have been noted, with a mean
      failure rate of 30% reported in four recent studies. A partial wrap
      fundoplication for GER associated with EA/TEF is theoretically attractive,
      because the poor esophageal motility and diminished acid clearance (already
      physiologically present) is exacerbated by a complete wrap fundoplication. The
      authors reviewed their extensive experience with partial wrap (Thal)
      fundoplication in EA/TEF to determine if the failure rate was better than that
      reported for the Nissen fundoplication. In the past 18 years, the authors
      performed 1,467 fundoplication procedures. During the same period, 143 children
      underwent repair of EA/TEF. Fifty-nine children underwent fundoplication after a
      previous EA/TEF repair. Most of the fundoplications (58 of 59, 98%) were Thal
      procedures. Defining failure strictly as a need for reoperation, the failure rate
      in our series was 15% (9 of 59 children). Compared with the failure rate in the
      1,408 non-EA/TEF patients (61 of 1408, 4.3%), results were significantly worse
      for the EA/TEF group (P > .001). The failure rate of Thal fundoplication
      performed for GER in the EA/TEF population is substantially higher than the non
      EA/TEF patients. The same factors responsible for the development of reflux in
      these children (poor acid clearance, altered motility, esophageal shortening) may
      contribute to the higher failure rate. Although partial wrap fundoplication
      frequently failed (15%), the results were still substantially better than those
      reported for Nissen fundoplication in these children (30% failure rate).

PMID- 9247241
TI  - Computed tomography grade of splenic injury is predictive of the time required
      for radiographic healing.
AB  - It is largely unknown when a child who has suffered a splenic laceration can
      return to full unrestricted activity. The purpose of this prospective study is to
      establish whether the grade of splenic injury is predictive of the length of time
      required for radiographic healing, and to determine whether there are any adverse
      long-term sequelae after resumption of unlimited activity. Sixty-nine patients
      underwent successful nonoperative management (NOM) of computed tomography (CT)
      documented splenic injury over a 4-year period. Fifty-eight patients completed
      follow-up. Mean age was 9.8 years (range, 1 to 17) and mean injury severity score
      (ISS) was 14.4 (range, 4 to 38). Mechanisms of injury were motor vehicle accident
      (n = 11), motor vehicle pedestrian (n = 5), falls (n = 13), bike crashes (n =
      12), sports (n = 8), all-terrain vehicle (n = 4), and horse (n = 5). The CT
      documented injury was identified by discharge ultrasound scan (US) in all cases.
      There were no long-term complications. Mean time to US healing in grade I (n =
      9), II (n = 26), III (n = 19), IV (n = 4) injuries was 3.1, 8.2, 12.1, and 20.7
      weeks, respectively. P values were significant (P < .01) in all cases when
      compared with the next lower injury grade. The time to radiographic healing is
      directly proportional to the severity of the splenic injury. There was excellent
      correlation between the initial CT scan and identification of the injury on the
      discharge US. No long-term complications leg, delayed splenic rupture, splenic
      pseudocyst) were seen in this study. Pediatric patients who have suffered splenic
      injury can safely return to full unrestricted activity when the US documents
      healing.

PMID- 9247243
TI  - The improved outlook for biliary atresia with corticosteroid therapy.
AB  - Controversy exists regarding the efficacy of corticosteroids on bile flow after
      Kasai portoenterostomy in biliary atresia (BA). Fourteen patients who had BA and
      underwent Kasai portojejunostomy between November 1990 and March 1996 were
      subject of this study. Corticosteroid therapy ("blast" type) was used for
      inadequate bile drainage. Corticosteroid support was unnecessary in one patient
      with good bile drainage, and corticosteroids were aggressively used in the
      remaining 13 patients. Two patients who had no response to an initial blast
      subsequently responded and now are doing well. The remaining 11 patients
      responded to corticosteroids with varying degrees. Three had a limited response,
      and two ultimately underwent liver transplantation. There was one death caused by
      subdural hematoma. Three had an excellent initial response. However, one
      subsequently deteriorated because of intractable cholangitis, requiring liver
      transplantation. Ten survivors with native liver are anicteric with satisfactory
      growth and quality of life. Aggressive corticosteroid therapy is an important
      part of the management after Kasai portoenterostomy. The initial response to
      steroids does not necessarily reflect the final outcome.

PMID- 9247242
TI  - Complications after cyst excision with hepaticoenterostomy for choledochal cysts
      and their surgical management in children versus adults.
AB  - The aim of this study was to review the cases 200 children and 40 adults who had
      cyst excision combined with hepaticoenterostomy (CEHE) for choledochal cyst, with
      particular emphasis on post-CEHE complications and their surgical management.
      Patients who had CEHE at the age of 15 years or less were defined as children,
      and those aged 16 years or older were defined as adults. The mean age when
      patients became initially symptomatic was 3 years in children and 26 years in
      adults. Eleven adults became symptomatic as children (< or = 15 years of age).
      The mean age of CEHE in children and adults was 4.2 years and 35 years,
      respectively. The time interval between the onset of initial symptoms and CEHE
      was significantly less in children than in adults (P < .0001). Of the 200
      children, 176 had primary CEHE, and 24 had secondary CEHE converted from
      cystoenterostomy or other biliary surgery. Seventy children had intraoperative
      cyst endoscopy, which enabled us to examine the proximal intrahepatic bile ducts
      for stenosis and debris, and to wash out debris, protein plugs, and stones from
      the intrapancreatic ducts. Of the 40 adults, 22 had primary CEHE, 18 had
      secondary CEHE. The mean follow-up period was 10.9 years in children and 10.7
      years in adults. The number of patients with post-CEHE complications in children
      and adults was 18 (9.0%) and 17 (42.5%), respectively. The post-CEHE complication
      rate in children was significantly lower than in adults (P < .0001). The 18
      children had 25 post-CEHE complications such as cholangitis, intrahepatic bile
      duct stones, pancreatitis, stone formation in the intrapancreatic terminal
      choledochus or pancreatic duct, and bowel obstruction. Twenty-seven post-CEHE
      complications developed in the 17 adults including 2 cases of cholangiocarcinoma.
      There were no post-CEHE complications in the 70 children who had intraoperative
      cyst endoscopy. No stone formation was seen in the 145 children who had CEHE at
      the age of 5 years or less. Eight stone formations were seen in seven (12.7%) of
      the remaining 55 children aged over 5 years. Stones developed in seven (17.5%)
      adults. The incidence of post-CEHE stone formation in children aged 5 years or
      less was significantly lower than in other children and adults (P < .0001).
      Reoperation was required in 15 children: revision of hepaticoenterostomy in 4,
      percutaneous transhepatic cholangioscopic lithotomy (PTCSL) in 1, excision of
      intrapancreatic terminal choledochus in 2, endoscopic sphincterotomy of the
      papilla of Vater in 1, pancreaticojejunostomy in 1, and laparotomy for bowel
      obstruction in 6. Ten adults required reoperations: revision of
      hepaticoenterostomy in 2, PTCSL in 2, left hepatic lobectomy in 1, endoscopic
      sphincterotomy in 2, exploratory laparotomy in 2, and adhesiolysis in 1. The
      authors conclude that early diagnosis followed by CEHE is the treatment of choice
      for choledochal cyst, and intraoperative cyst endoscopy is recommended as a
      valuable adjunct to CEHE.

PMID- 9247244
TI  - Reoperation after pericardial patch tracheoplasty.
AB  - Between 1982 and 1995, 28 infants underwent pericardial tracheoplasty for long
      segment tracheal stenosis. Seven of these infants required reoperation or
      stenting for residual or recurrent tracheal or bronchial stenosis. Revisions were
      performed 2 to 6 months after the original procedure with cardiopulmonary bypass
      and bronchoscopic guidance. Two patients underwent repeat pericardial patch
      tracheoplasty, and four patients underwent insertion of a rib cartilage graft.
      Two of these patients required Palmaz wire expandable stents and one other
      patient also underwent stent placement. There was one late death 1 year after
      cartilage graft insertion. The authors identified three risk factors for
      reoperation after tracheoplasty; younger age at initial surgery and associated
      pulmonary artery sling or tracheal right upper lobe bronchus. Good intermediate
      results are possible in this difficult group of children using a selective and
      inclusive strategy for tracheal enlargement that includes repeat pericardial
      tracheoplasty, autologous cartilage grafts, and expandable wire stents.

PMID- 9247245
TI  - Prenatal therapy for pericardial teratomas.
AB  - Although the majority of reported pericardial teratomas have been excised
      successfully in the postnatal period, the outcome of prenatally diagnosed
      pericardial teratomas remains less favorable. Two recent cases of prenatally
      diagnosed pericardial teratomas and a review of previously reported cases suggest
      a new management algorithm for those pericardial teratomas discovered in utero.
      Fetuses in whom hydrops does not develop may be safely followed up and treated
      postnatally. However, if hydrops develops, the fetus requires treatment with
      either aspiration of the pericardial effusion, or fetal surgery and resection.

PMID- 9247246
TI  - The management of choledocholithiasis in children in the era of laparoscopic
      cholecystectomy.
AB  - Although laparoscopic cholecystectomy has become the procedure of choice for
      gallbladder removal in children, the treatment of children who have
      choledocholithiasis remains unclear. For adults who have suspected
      choledocholithiasis, preoperative endoscopic retrograde cholangiopancreatography
      (ERCP) is a well-described and effective approach, however, its use for common
      bile duct stones in children has not been defined. The authors reviewed the
      records of 131 consecutive children undergoing laparoscopic cholecystectomy on
      two surgical services to define the efficacy of ERCP followed by laparoscopic
      cholecystectomy in managing choledocholithiasis in children. Fourteen children
      were suspected of having common duct stones noted on preoperative ultrasound scan
      and laboratory data. At ERCP, six children had no stones visualized; eight had
      stones and underwent stone extraction and sphincter dilation or sphincterotomy.
      All 14 underwent laparoscopic cholecystectomy a mean of 3.8 days after ERCP. None
      of the 14 had evidence of retained stones. Only one of 117 children undergoing
      primary laparoscopic cholecystectomy had unsuspected common bile duct stones and
      was treated with laparoscopic common bile duct exploration and stone removal. A
      management plan incorporating ERCP followed by early laparoscopic cholecystectomy
      is a safe and effective strategy for children who have choledocholithiasis.

PMID- 9247247
TI  - Video-assisted thoracoscopic diskectomy and fusion.
AB  - Thoracoscopic diskectomy has been described in adults as an alternative to
      thoracotomy for access to the anterior spine for correction of scoliosis, but its
      use in children for correction of spinal deformities has not been reported. Eight
      patients have undergone video-assisted thoracoscopic diskectomy with fusion
      before posterior instrumentation. In five patients, the posterior fusion and
      instrumentation followed the thoracoscopic procedure under the same anesthesia;
      in three patients it was staged and performed 1 week later. The mean time
      required for the thoracoscopic procedure was 174 minutes. Intraoperative bleeding
      requiring transfusion developed in one patient. No other complications occurred.
      The authors conclude that the minimally invasive approach for access to the
      thoracic cavity for anterior diskectomy and fusion will be the preferred approach
      because of the potential for significant reduction in postoperative discomfort
      and complications such as atelectasis and pneumonia. Postoperative
      hospitalization may not be decreased, however, because the patient must still
      recover from the open posterior instrumentation and fusion operation.

PMID- 9247248
TI  - Endotoxin and transient hypoxia cause severe acidosis in the piglet.
AB  - PURPOSE: Both hypoxia and gram-negative sepsis are thought to play a role in the
      development of necrotizing enterocolitis (NEC). Endotoxin, a lipopolysaccharide
      (LPS), is a potent mediator of gram-negative sepsis. The author investigated the
      effect of LPS and hypoxia on arterial and mesenteric venous blood gas values in a
      piglet model. METHODS: 16 piglets (mean age, 9 days; mean weight, 3.2 kg) were
      anesthetized and mechanically ventilated. Catheters were placed in the aorta and
      the superior mesenteric vein (SMV). After a 30-minute stabilization period,
      piglets were randomly assigned to four experimental groups: normoxic ventilation
      (FIO2, 0.21), normoxic ventilation and LPS infusion (200 microg/kg,
      intravenously), hypoxic ventilation (FIO2, 0.10 for 20 minutes), or hypoxic
      ventilation and LPS infusion. All subjects were then monitored for an additional
      30 minutes (recovery period). Multiple, paired blood gas samples were obtained
      from the aorta and SMV during the stabilization, experimental, and recovery
      periods. RESULTS: Piglets subjected to both hypoxia and LPS experienced a much
      more severe acidosis in both the aorta (pH, 7.10 +/- 0.08) and SMV (pH, 7.03 +/-
      0.09) than piglets subjected to either hypoxia or LPS alone (P < .05). In
      addition, LPS lowered the arterial oxygen saturation in piglets exposed to acute,
      transient hypoxia (36 +/- 4% v 59 +/- 12%, P < .05). CONCLUSION: This study
      suggests that the combination of transient hypoxia and gram-negative sepsis may
      act synergistically to produce both a severe acidosis and decreased tissue
      oxygenation.

PMID- 9247249
TI  - Video-assisted thoracoscopic pneumonectomy for bronchial carcinoid tumor in a 14
      year-old girl.

PMID- 9247250
TI  - An examination of the effects of hypoxia, acidosis, and glucose starvation on the
      expression of metastasis-associated genes in murine tumor cells.
AB  - Tumor cells exposed to a growth stress such as low pH, glucose starvation and
      hypoxia have been shown to exhibit a transient increase in experimental
      metastatic potential, particularly when allowed to recover under normal growth
      conditions for a period of 24-48 h. In this study we examined whether this
      increase in metastatic ability could be explained by changes in the expression of
      a number of different metastasis-associated genes, when the cells were exposed to
      similar conditions (24-48 h exposure to the stress condition followed by 0-48 h
      recovery under normal growth conditions). Although the cell lines used (KHT
      fibrosarcoma, SCC VII squamous cell carcinoma, and B16F1 melanoma) demonstrated
      altered metastatic ability after the treatment, no overall temporal correlation
      between changes in the mRNA levels for cathepsin B, cathepsin L, nm23, TIMP-1,
      osteopontin, or VEGF and metastatic ability in the three cell lines was observed.
      The production of gelatinase A (72 kDa collagenase) and gelatinase B (92 kDa
      collagenase) was also measured by gelatin zymography. There was an increase in
      production of these enzymes with increasing recovery time, but it did not
      parallel changes in metastatic potential. Although these results suggest that the
      products of most of the genes studied may not be involved in the transient
      metastatic changes, further studies are required to establish whether changes in
      protein levels track with changes in mRNA levels for these genes.

PMID- 9247251
TI  - Blood vessels in liver metastases from both sarcoma and carcinoma lack
      perivascular innervation and smooth muscle cells.
AB  - Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal
      liver metastases is promising, but not entirely satisfactory. Improved drug
      delivery during HAI may be achieved by manipulating the different control
      mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic
      innervation of vessels in normal liver and in two animal models of liver
      metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat
      with human HT29 carcinoma) was investigated to assess the suitability of these
      models for future pharmacological studies. Normal liver and metastases were
      studied immunohistochemically for the presence of protein gene product 9.5 (PGP),
      neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide
      (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP).
      Perivascular innervation was also examined by transmission electron microscopy.
      In Lister rat normal livers, perivascular immunoreactive nerve fibres containing
      PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels
      near the hilum and in the portal tracts. The highest density was seen for PGP,
      followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves
      were absent. No immunoreactive nerves were observed in the hepatic lobule. In
      athymic rat livers, the pattern of innervation was similar, except that SP
      immunoreactivity was more sparse. No perivascular immunoreactive nerves were
      observed in either MC28 or HT29 tumours. Electron microscopy confirmed the
      absence of perivascular nerves. Smooth muscle cells were not observed in tumour
      blood vessel walls. These results are comparable with previous observations on
      human liver metastases and suggest that the animal models may be suitable for
      pharmacological studies on vascular manipulation of HAI chemotherapy.

PMID- 9247252
TI  - Rodent pharmacokinetic and anti-tumor efficacy studies with a series of synthetic
      inhibitors of matrix metalloproteinases.
AB  - Matrix metalloproteinases are a family of zinc-containing proteases that degrade
      extracellular matrix and basement membranes. These enzymes are thought to play a
      role in processes essential for tumor growth, invasion, and metastasis. Here we
      report pharmacokinetic and anti-tumor efficacy studies with a series of
      structurally related inhibitors of these enzymes that were synthesized at Agouron
      Pharmaceuticals using protein structure based drug design. The compounds studied
      were AG3287, AG3293, AG3294, AG3296, AG3319, and AG3340. Rat oral bioavailability
      ranged from 15 to 68%. Despite similar profiles of enzyme inhibition across the
      family of enzymes, and similar pharmacokinetics following i.p. administration to
      mice, efficacy against the Lewis lung carcinoma murine model varied from tumor
      growth enhancement, to significant reductions in the size of primary tumors and
      the number of lung metastases. AG3340 was the most efficacious compound against
      the Lewis lung carcinoma model, resulting in the complete cessation of primary
      tumor growth throughout the experiment in 4/6 mice treated with daily i.p.
      injections at a dose of 50 mg/kg. This treatment inhibited the formation of lung
      metastases greater than 5 mm in diameter by 90%.

PMID- 9247253
TI  - Expression of MAGE genes in ocular melanoma during progression from primary to
      metastatic disease.
AB  - Primary melanomas that form within the eye have a unique pattern of disease
      progression as compared with melanomas that form within the skin. A high
      percentage of patients (approximately 50%) develop metastatic tumors that occur
      predominately in the liver. An unusual characteristic of ocular melanomas is the
      prolonged disease-free interval that extends for many years between the
      development of primary and metastatic tumors. It is estimated that the shortest
      interval between dissemination of tumor cells from the eye and the appearance of
      clinically detectable metastases is 6 years. A recent report indicated that fresh
      uveal melanoma tissue and metastatic tumor biopsies failed to express melanoma
      antigen gene (MAGE)-1, MAGE-2, or MAGE-3. In the present study, we examined the
      expression of MAGE genes on fresh and cultured tumor cells obtained from an
      ocular melanoma patient during different stages of progressive disease. MAGE gene
      expression was determined by reverse transcription-polymerase chain reaction
      using MAGE-1, MAGE-2 and MAGE-3 specific primers. Our results demonstrate that
      primary ocular tumor tissue and cultured tumor cells both express significant
      levels of MAGE-1, 2, and 3 at the time of enucleation. A high percentage of tumor
      cells within the primary tumor appear to express MAGE as demonstrated by
      consistent MAGE expression in 16 tumor cell clones. Metastatic liver tumors that
      developed 3 years after enucleation and 18 years after the initial formation of
      the primary tumor also expressed high levels of MAGE-1, -2, and -3. MAGE was
      expressed on fresh tumor tissue from a single biopsy and cultured tumor cells
      obtained from three of four different metastatic tumor nodules. When the MAGE
      negative metastatic tumor cells were treated with the demethylating agent 5-Aza-2
      Deoxycytidine (5-Aza-dC), transcription of MAGE-1 was restored, indicating the
      MAGE genes were not deleted. Our results demonstrate that in some patients, MAGE
      genes are expressed on primary and metastatic ocular melanomas.

PMID- 9247254
TI  - Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype
      in breast carcinoma cell lines.
AB  - We have previously observed in vitro that some stromal proteinases (MMP-2, MT1
      MMP) were expressed or activated by invasive carcinoma cell lines exhibiting
      mesenchymal features, presumably acquired through an epithelial to mesenchymal
      transition (EMT). To examine the potential contribution of c-ets-1 to this
      phenotype, we have compared here the expression of c-ets-1 with invasiveness in
      vitro and expression of vimentin, E-cadherin, uPA, MMP-1 and MMP-3 in a panel of
      human breast cancer cell lines. Our results clearly demonstrate an association
      between c-ets-1 expression and the invasive, EMT-derived phenotype, which is
      typified by the expression of vimentin and the lack of E-cadherin. While absent
      from the two non-invasive, vimentin-negative cell lines, c-ets-1 was abundantly
      expressed in all the four vimentin-positive lines. However, we could not find a
      clear quantitative or qualitative relationship between the expression of c-ets-1
      and the three proteinases known to be regulated by c-ets-1, except that when they
      were expressed, it was only in the invasive c-ets-1-positive lines. UPA mRNAs
      were found in three of the four vimentin-positive lines, MMP-1 in two of the
      four, and MMP-3 could not be detected in any of the cell lines. Intriguingly, MDA
      MB-435 cells, which exhibit the highest metastatic potential of these cell lines
      in nude mice, expressed vimentin and c-ets-1, but lacked expression of these
      three proteinases, at least under the culture conditions employed. Taken
      together, our results show that c-ets-1 expression is associated with an
      invasive, EMT-derived phenotype in breast cancer cells, although it is apparently
      not sufficient to ensure the expression of uPA, MMP-1 or MMP-3, in the vimentin
      positive cells. Such proteases regulation is undoubtedly qualified by the
      cellular context. This study therefore advances our understanding of the
      molecular regulation of invasiveness in EMT-associated carcinoma progression, and
      suggests that c-ets-1 may contribute to the invasive phenotype in carcinoma
      cells.

PMID- 9247255
TI  - Metastatic variants derived following in vivo tumor progression of an in vitro
      transformed squamous cell carcinoma line acquire a differential growth advantage
      requiring tumor-host interaction.
AB  - The purpose of this study was to develop an experimental model of squamous cell
      carcinoma that can be used to identify molecular and immunologic changes
      associated with primary events in malignant transformation, and those associated
      with metastatic tumor progression in the presence of host homeostatic and
      immunologic factors. Metastatic variants were derived following in vivo tumor
      progression of the in vitro transformed squamous cell carcinoma line Pam 212. The
      parental and metastatic cell lines exhibited similar morphologic features and
      molecular markers of an epithelial lineage, including an epithelial morphology in
      culture, cell surface expression of integrin alpha6beta4, and expression of mRNA
      of cytokeratins K6 and K14. When the growth and metastatic phenotype of the
      parental and reisolate cell lines was compared, the reisolate cell lines were
      found to exhibit a greater rate of growth and incidence of metastasis than the
      parental cell line when reimplanted in vivo. The difference in the growth rate of
      the parental cell line and the variants observed in vivo was not detected when
      growth of these lines was compared in vitro, suggesting that the growth advantage
      and selection of these variants requires tumor-host interaction. The metastatic
      variants exhibited a similar growth advantage in normal immunocompetent and SCID
      Balb/c mice, indicating that the growth advantage in vivo is not due to T or B
      lymphocyte-dependent immune factor(s). We conclude that metastatic variants
      derived following in vivo tumor progression of an in vitro transformed squamous
      cell carcinoma line exhibit a differential growth advantage in vivo that requires
      the host environment. Comparison of these in vitro transformed and in vivo
      derived metastatic variant cell lines with phenotypic differences in growth and
      metastasis should prove useful for dissecting the role of tumor and host
      factor(s) in malignant transformation and metastatic tumor progression of
      squamous cell carcinoma.

PMID- 9247256
TI  - Fibronectin-mediated cell migration promotes glioma cell invasion through
      chemokinetic activity.
AB  - In order to investigate the biological role of fibronectin in glioma cell
      invasion, we studied the relation between migratory responses or adhesiveness of
      glioma cells to fibronectin and the in vitro invasion in three human malignant
      glioma cell lines, A172, T98G and U373MG. All these cell lines chemotactically
      migrated in a dose-dependent manner to fibronectin in concentrations ranging from
      0.5 to 10 microg/ml, with A172 cells showing the strongest migration and U373
      cells the weakest. Checkerboard analyses demonstrated that A172 and T98G cells
      showed much stronger chemokinetic responses to fibronectin than U373MG cells. In
      contrast to the migratory responses, A172 and U373MG cells showed an almost
      equally high adhesion to fibronectin and T98G cells a low adhesion. The degree of
      expression of the integrin alpha5 subunit correlated well with the strength of
      glioma cell adhesion to fibronectin rather than that of migration to the
      molecule. Furthermore, the cell adhesion to fibronectin was almost completely
      inhibited by arginine-glycine-aspartic acid (RGD)-containing peptides, but the
      fibronectin-stimulated cell migration was only partially inhibited. An in vitro
      invasion assay disclosed that U373MG cells invaded the artificial basement
      membrane barrier the most and A172 cells the least. However, addition of
      fibronectin to the glioma cells markedly enhanced the invasive activity of A172
      and T98G cells but had little effect on that of U373MG cells. These results
      indicate that fibronectin-stimulated migration can be one of the factors
      promoting invasiveness of glioma cells and that the chemokinetic activity of
      fibronectin may play a crucial role in glioma invasion through conferring motor
      driving force on the glioma cells.

PMID- 9247258
TI  - Dynamic synapses in the cortex.

PMID- 9247257
TI  - Metastatic patterns of lung cancer visualized live and in process by green
      fluorescence protein expression.
AB  - We demonstrate here the visualization of human lung cancer metastasis live and in
      process in nude mice by green fluorescent protein (GFP) expression. The human
      lung adenocarcinoma cell line Anip 973 stably transfected with the humanized GFP
      S65T cDNA was selected for very bright green fluorescence. GFP-transfected lung
      cancer cells were initially inoculated subcutaneously in nude mice. Five weeks
      after transplantation, the resulting tumor had reached over 1 cm in diameter and
      had very bright GFP fluorescence. Fragments of subcutaneous tumor were implanted
      onto the visceral pleura of the left lung of nude mice by surgical orthotopic
      implantation (SOI) of histologically-intact tissue via transverse thoracotomy.
      The ipsilateral resulting tumor was highly fluorescent due to GFP expression. GFP
      expression allowed the visualization of the advancing margin of the ipsilateral
      tumor into the fresh normal lung tissue. Lymphogenous and direct-seeding
      metastases in the pulmonary hilum, cervical lymph nodes, the mediastinum and
      contralateral pleural cavity and contralateral lung in the SOI-treated mice were
      brightly visualized by GFP expression in fresh tissue. GFP-transfected and
      untransfected tumor had similar metastatic characteristics suggesting that GFP
      expression had no effect on metastasis itself. The results with the GFP
      transfected tumor cells, combined with the use of SOI, demonstrate a fundamental
      advance in the visualization and study of lung cancer metastasis in process.

PMID- 9247259
TI  - Giga-ohm seals on intracellular membranes: a technique for studying intracellular
      ion channels in intact cells.
AB  - A method is outlined for obtaining giga-ohm seals on intracellular membranes in
      intact cells. The technique employs a variant of the patch-clamp technique: a
      concentric electrode arrangement protects an inner patch pipette during
      penetration of the plasma membrane, after which a seal can be formed on an
      internal organelle membrane. Using this technique, successful recordings can be
      obtained with the same frequency as with conventional patch clamping. To localize
      the position of the pipette within cells, lipophilic fluorescent dyes are
      included in the pipette solution. These dyes stain the membrane of internal
      organelles during seal formation and can then be visualized by video-enhanced or
      confocal imaging. The method can detect channels activated by inositol
      trisphosphate, as well as other types of intracellular membrane ion channel
      activity, and should facilitate studies of internal membranes in intact neurons
      and other cell types.

PMID- 9247260
TI  - Control of cell pattern in the neural tube by the zinc finger transcription
      factor and oncogene Gli-1.
AB  - Sonic hedgehog (Shh) is a putative morphogen secreted by the floor plate and
      notochord, which specifies the fate of multiple cell types in the ventral aspect
      of the vertebrate nervous system. Since in Drosophila the actions of Hh have been
      shown to be transduced by Cubitus interruptus (Ci), a zinc finger transcription
      factor, we examined whether a vertebrate homolog of this protein can mediate the
      functions of Shh in the vertebrate nervous system. Here, we demonstrate that
      expression of Gli-1, one of three vertebrate homologs of Ci, can be induced by
      Shh in the neural tube. Further, ectopic expression of Gli-1 in the dorsal
      midbrain and hindbrain of transgenic mice mimics the effects of ectopically
      expressed Shh-N, leading to the activation of ventral neural tube markers such as
      Ptc, HNF-3beta, and Shh; to the suppression of dorsal markers such as Pax-3 and
      AL-1; and to the formation of ectopic dorsal clusters of dopaminergic and
      serotonergic neurons. These findings demonstrate that GLI-1 can reproduce the
      cell patterning actions of Shh in the developing nervous system and provide
      support for the hypothesis that it is a mediator of the Shh signal in
      vertebrates.

PMID- 9247261
TI  - Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal
      subventricular zone and differentiation of late born striatal neurons.
AB  - The striatum has a central role in many neurobiological processes, yet little is
      known about the molecular control of its development. Inroads to this subject
      have been made, due to the discovery of transcription factors, such as the Dlx
      genes, whose expression patterns suggest that they have a role in striatal
      development. We report that mice lacking both Dlx-1 and Dlx-2 have a time
      dependent block in striatal differentiation. In these mutants, early born neurons
      migrate into a striatum-like region, which is enriched for markers of the
      striosome (patch) compartment. However, later born neurons accumulate within the
      proliferative zone. Several lines of evidence suggest that mutations in Dlx-1 and
      Dlx-2 produce abnormalities in the development of the striatal subventricular
      zone and in the differentiation of striatal matrix neurons.

PMID- 9247262
TI  - Neuregulin and erbB receptors play a critical role in neuronal migration.
AB  - The migration of neuronal precursors along radial glial fibers is a critical step
      in the formation of the nervous system. In this report, we show that neuregulin
      erbB receptor signaling plays a crucial role in the migration of cerebellar
      granule cells along radial glial fibers. Granule cells express neuregulin (NRG),
      and radial glia cells express erbB4 in the developing cerebellum and in vitro.
      When the glial erbB receptors are blocked, neurons fail to induce radial glia
      formation, and their migration along radial glial fibers is impaired. Moreover,
      soluble NRG is as effective as neuron-glia contact in the induction of radial
      glia formation. These results suggest that the activation of glial erbB4 by NRG
      is an early critical step in the neuronal migration program.

PMID- 9247263
TI  - Neuronal migrations and axon fasciculation are disrupted in ina-1 integrin
      mutants.
AB  - Integrins are heterodimeric cell surface receptors implicated in cell adhesion
      and signaling. Our analysis of C. elegans ina-1 alpha integrin mutants provides
      the first genetic evidence that migrating neurons require integrins. Mosaic
      analysis and expression studies show that ina-1 acts autonomously in cells to
      promote their migrations. Although axons generally extend to their normal targets
      in ina-1 mutants, bundling of axons into fascicles is defective, defining a
      previously unrecognized role for integrins. In addition to these neuronal
      phenotypes, ina-1 mutants also display many morphogenetic defects. Finally, we
      show that the C. elegans INA-1 alpha integrin subunit associates with the PAT
      3beta subunit in vivo, suggesting that these proteins function together in cell
      migration, axon fasciculation, and morphogenesis.

PMID- 9247264
TI  - Blockade of endogenous ligands of trkB inhibits formation of ocular dominance
      columns.
AB  - We have examined the hypothesis that the segregation of LGN axon terminals into
      ocular dominance (OD) patches in layer 4 of the visual cortex requires
      neurotrophins, acting as signals to modulate the pattern of synaptic
      connectivity. Neurotrophin receptor antagonists, composed of the extracellular
      domain of each member of the trk family of neurotrophin receptors fused to a
      human Fc domain, were infused directly into visual cortex during the peak phase
      of OD column formation. Infusion of trkB-IgG, which binds BDNF and NT-4/5,
      inhibited the formation of OD patches within layer 4, while trkA-IgG and trkC
      IgG, which preferentially bind NGF and NT-3, respectively, had no effect. The
      autoradiographic labeling of LGN terminals in cortical layer 4 was reduced by
      trkB-IgG, in contrast with the increased labeling observed following NT-4/5
      infusion. These data suggest that an endogenous ligand of trkB, normally present
      in limiting amounts within visual cortex, is necessary for the selective growth
      and remodeling of LGN axons into eye-specific patches.

PMID- 9247265
TI  - Axon patterning requires DN-cadherin, a novel neuronal adhesion receptor, in the
      Drosophila embryonic CNS.
AB  - We identified DN-cadherin, a novel Drosophila cadherin that is expressed in axons
      and in the mesoderm. Although DN-cadherin has diverged from vertebrate classic
      cadherins in terms of its extracellular structure, it still can form a complex
      with catenins and induce cell aggregation, as do the vertebrate molecules. Loss
      of-function mutations of the gene resulted in either embryonic lethality or
      uncoordinated locomotion of adults. In the central nervous system of null mutant
      embryos, subsets of ipsilateral axons displayed a variety of aberrant
      trajectories including failure of position shifts, defective bundling, and errors
      in directional migration of growth cones. These results suggest that processes of
      axon patterning critically depend on DN-cadherin-mediated axon-axon interactions.

PMID- 9247266
TI  - Molecular dissection of two distinct actions of melatonin on the suprachiasmatic
      circadian clock.
AB  - The pineal hormone melatonin elicits two effects on the suprachiasmatic nuclei
      (SCN): acute neuronal inhibition and phase-shifting. Melatonin evokes its
      biological effects through G protein-coupled receptors. Since the Mel1a melatonin
      receptor may transduce the major neurobiological actions of melatonin in mammals,
      we examined whether it mediates both melatonin effects on SCN function by using
      mice with targeted disruption of the Mel1a receptor. The Mel1a receptor accounts
      for all detectable, high affinity melatonin binding in mouse brain. Functionally,
      this receptor is necessary for the acute inhibitory action of melatonin on the
      SCN. Melatonin-induced phase shifts, however, are only modestly altered in the
      receptor-deficient mice; pertussis toxin still blocks melatonin-induced phase
      shifts in Mel1a receptor-deficient mice. The other melatonin receptor subtype,
      the Mel1b receptor, is expressed in mouse SCN, implicating it in the phase
      shifting response. The results provide a molecular basis for two distinct,
      mechanistically separable effects of melatonin on SCN physiology.

PMID- 9247267
TI  - Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2
      receptor-deficient mice.
AB  - Dopamine secreted from hypophysial hypothalamic neurons is a principal inhibitory
      regulator of pituitary hormone secretion. Mice with a disrupted D2 dopamine
      receptor gene had chronic hyperprolactinemia and developed anterior lobe
      lactotroph hyperplasia without evidence of adenomatous transformation.
      Unexpectedly, the mutant mice had no hyperplasia of the intermediate lobe
      melanotrophs. Aged female D2 receptor -/- mice developed uterine adenomyosis in
      response to prolonged prolactin exposure. These data reveal a critical role of
      hypothalamic dopamine in controlling pituitary growth and support a multistep
      mechanism for the induction and perpetuation of lactotroph hyperplasia, involving
      the lack of dopamine signaling, a low androgen/estrogen ratio, and a final
      autocrine or paracrine "feed-forward" stimulation of mitogenesis, probably by
      prolactin itself.

PMID- 9247268
TI  - Antiproliferative role of dopamine: loss of D2 receptors causes hormonal
      dysfunction and pituitary hyperplasia.
AB  - The function of dopamine (DA) in the nervous system is paralleled by its
      neuroendocrine control of pituitary gland functions. Here, we document the
      neuroendocrine function of dopamine by studying the pituitary gland of mice
      lacking DA D2 receptors (D2R). These mice present a striking, progressive
      increase in lactotroph number, which ultimately leads to tumors in aged animals.
      Females develop tumors much earlier than males. An estrogen-mediated lactotroph
      proliferation cannot account for this sexual dimorphism, since D2R-null females
      are hypoestrogenic and, thus, have estrogen levels similar to males. In contrast,
      prolactin levels are six times higher in females than in males. We show that
      active prolactin receptors are present in the pituitary and their expression
      increases in concomitance with tumor expansion. These results point to prolactin
      as an autocrine proliferative factor in the pituitary gland. Additionally, they
      demonstrate an antiproliferative function for DA regulated through D2 receptor
      activation.

PMID- 9247269
TI  - Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine
      transporter.
AB  - Deletion of the dopamine transporter (DAT) results in increased dopaminergic
      tone, anterior pituitary hypoplasia, dwarfism, and an inability to lactate. DAT
      elimination alters the spatial distribution and dramatically reduces the numbers
      of lactotrophs and somatotrophs in the pituitary. Despite having normal
      circulating levels of growth hormone and prolactin in blood, hypoplastic glands
      from DAT-/- mice fail to respond to secretagog stimulation. The effects of DAT
      deletion on pituitary function result from elevated DA levels that down-regulate
      the lactotroph D2 DA receptors and depress hypothalamic growth hormone-releasing
      hormone content. These results reveal an unexpected and important role or DA in
      the control of developmental events in the pituitary gland and assign a critical
      role for hypothalamic DA reuptake in regulating these events.

PMID- 9247270
TI  - Heterogeneity of functional synaptic parameters among single release sites.
AB  - Following alpha-latrotoxin application to cerebellar slices, bursts of miniature
      IPSCs (mIPSCs) were observed in interneurons of the molecular layer. Within
      bursts, mIPSCs had homogeneous amplitudes with a narrow Gaussian distribution.
      Analysis of successive event amplitudes revealed an interaction between
      consecutive IPSCs, indicating that bursts originate at single release sites. A
      mean receptor occupancy of 76% was calculated. IPSCs within a burst were analyzed
      using nonstationary noise analysis. The results indicate that individual release
      sites differ in the number, unitary conductance, and peak opening probability of
      their postsynaptic channels. In addition, the IPSC decay kinetics were very
      different among release sites. Finally, a significant correlation was found
      between several pairs of single site synaptic parameters.

PMID- 9247271
TI  - Behavioral defects in C. elegans egl-36 mutants result from potassium channels
      shifted in voltage-dependence of activation.
AB  - Mutations in the C. elegans egl-36 gene result in defective excitation of egg
      laying and enteric muscles. Dominant gain-of-function alleles inhibit enteric and
      egg-laying muscle contraction, whereas a putative null mutation has no observed
      phenotype. egl-36 encodes a Shaw-type (Kv3) voltage-dependent potassium channel
      subunit. In Xenopus oocytes, wild-type egl-36 expresses noninactivating channels
      with slow activation kinetics. One gain-of-function mutation causes a single
      amino acid substitution in S6, and the other causes a substitution in the
      cytoplasmic amino terminal domain. Both mutant alleles produce channels
      dramatically shifted in their midpoints of activation toward hyperpolarized
      voltages. An egl-36::gfp fusion is expressed in egg-laying muscles and in a pair
      of enteric muscle motor neurons. The mutant egl-36 phenotypes can thus be
      explained by expression in these cells of potassium channels that are
      inappropriately opened at hyperpolarized potentials, causing decreased
      excitability due to increased potassium conductance.

PMID- 9247272
TI  - EGL-36 Shaw channels regulate C. elegans egg-laying muscle activity.
AB  - The C. elegans egl-36 gene encodes a Shaw-type potassium channel that regulates
      egg-laying behavior. Gain of function [egl-36(gf)] and dominant negative [egl
      36(dn)] mutations in egl-36 cause reciprocal defects in egg laying. An egl
      36::gfp reporter is expressed in the egg-laying muscles and in a few other
      tissues. Expression of an egl-36(gf) cDNA in the egg-laying muscles causes
      behavioral defects similar to those observed in egl-36(gf) mutants. Gain of
      function EGL-36 subunits form channels that are active at more negative
      potentials than wild-type channels. The egl-36(gf) alleles correspond to missense
      mutations in an amino terminal subunit assembly domain (E138K) and in the S6
      transmembrane domain (P435S), neither of which were previously implicated in the
      voltage dependence of channel activation. Altogether, these results suggest that
      EGL-36 channels regulate the excitability of the egg-laying muscles.

PMID- 9247273
TI  - Gated access to the pore of a voltage-dependent K+ channel.
AB  - Voltage-activated K+ channels are integral membrane proteins that open or close a
      K(+)-selective pore in response to changes in transmembrane voltage. Although the
      S4 region of these channels has been implicated as the voltage sensor, little is
      known about how opening and closing of the pore is accomplished. We explored the
      gating process by introducing cysteines at various positions thought to lie in or
      near the pore of the Shaker K+ channel, and by testing their ability to be
      chemically modified. We found a series of positions in the S6 transmembrane
      region that react rapidly with water-soluble thiol reagents in the open state but
      not the closed state. An open-channel blocker can protect several of these
      cysteines, showing that they lie in the ion-conducting pore. At two of these
      sites, Cd2+ ions bind to the cysteines without affecting the energetics of
      gating; at a third site, Cd2+ binding holds the channel open. The results suggest
      that these channels open and close by the movement of an intracellular gate,
      distinct from the selectivity filter, that regulates access to the pore.

PMID- 9247274
TI  - cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane
      targeting of PKA and phosphorylation of channel subunits.
AB  - The cardiac L-type Ca2+ channel is a textbook example of an ion channel regulated
      by protein phosphorylation; however, the molecular events that underlie its
      regulation remain unknown. Here, we report that in transiently transfected HEK293
      cells expressing L-type channels, elevations in cAMP resulted in phosphorylation
      of the alpha1C and beta2a channel subunits and increases in channel activity.
      Channel phosphorylation and regulation were facilitated by submembrane targeting
      of protein kinase A (PKA), through association with an A-kinase anchoring protein
      called AKAP79. In transfected cells expressing a mutant AKAP79 that is unable to
      bind PKA, phosphorylation of the alpha1C subunit and regulation of channel
      activity were not observed. Furthermore, we have demonstrated that the
      association of an AKAP with PKA was required for beta-adrenergic receptor
      mediated regulation of L-type channels in native cardiac myocytes, illustrating
      that the events observed in the heterologous expression system reflect those
      occurring in the native system. Mutation of Ser1928 to alanine in the C-terminus
      of the alpha1C subunit resulted in a complete loss of cAMP-mediated
      phosphorylation and a loss of channel regulation. Thus, the PKA-mediated
      regulation of L-type Ca2+ channels is critically dependent on a functional AKAP
      and phosphorylation of the alpha1C subunit at Ser1928.

PMID- 9247275
TI  - Endogenous progenitors remyelinate demyelinated axons in the adult CNS.
AB  - Remyelination occurs in demyelinated CNS regions in diseases such as multiple
      sclerosis. Identification of the cell type(s) responsible for this remyelination,
      however, has been elusive. Here, we examine one potential source of remyelinating
      oligodendrocytes-immature, cycling cells endogenous to adult white matter-and
      demonstrate that this population responds to demyelination by differentiating
      into myelinating oligodendrocytes. Dividing cells in subcortical white matter of
      adult rats were labeled by stereotactic injection of a replication-deficient lacZ
      encoding retrovirus (BAG). Following a focal demyelination induced with
      lysolecithin, many of the BAG-labeled cells differentiated into myelinating
      oligodendrocytes engaging in repair of the lesion. Identification of endogenous
      cells capable of remyelination provides a target for the study of CNS repair
      processes in demyelinating diseases.

PMID- 9247276
TI  - Proteolipid protein is necessary in peripheral as well as central myelin.
AB  - Alternative products of the proteolipid protein gene (PLP), proteolipid protein
      (PLP) and DM20, are major components of compact myelin in the central nervous
      system, but quantitatively minor constituents of Schwann cells. A family with a
      null allele of PLP has a less severe CNS phenotype than those with other types of
      PLP mutations. Moreover, individuals with PLP null mutations have a demyelinating
      peripheral neuropathy, not seen with other PLP mutations of humans or animals.
      Direct analysis of normal peripheral nerve demonstrates that PLP is localized to
      compact myelin. This and the clinical and pathologic observations of the PLP null
      phenotype indicate that PLP/DM20 is necessary for proper myelin function both in
      the central and peripheral nervous systems.

PMID- 9247277
TI  - Quantitative analysis of tryptase and chymase containing mast cells in benign and
      malignant breast lesions.
AB  - The aim of our work was to study the number and distribution of tryptase- and
      chymase-containing mast cells in benign and malignant breast lesions. Tryptase
      positivity reflects the total number of mast cells, whereas chymase is not
      present in all mast cells. Active forms of tryptase and chymase were demonstrated
      enzymo-histochemically in 30 benign and 98 malignant fresh frozen breast lesions,
      which were graded and analysed morphometrically and statistically. The exclusive
      presence of tryptase and chymase in mast cells was confirmed in 5 cases by a
      sequential double-staining method. In benign lesions, the number of mast cells
      exhibiting tryptase activity was similar to that of chymase-active mast cells.
      Malignant tumours, however, had 2 to 3 times more tryptase-containing than
      chymase-containing mast cells, while the number of mast cells with tryptase
      activity was significantly higher (p < 0.02) than in benign lesions. In malignant
      lesions, tryptase-containing mast cells were concentrated at the tumour edge,
      i.e., the "invasion zone," whereas chymase-containing mast cells were not
      increased in this area.

PMID- 9247278
TI  - Reproductive factors and the risk of brain tumors: a population-based study in
      Sweden.
AB  - Possible associations between childbearing and the risk of brain cancer were
      explored in a case-control study "nested" within a large nationwide cohort
      defined by the Swedish Fertility Registry. Among women born between 1925-1975,
      1,088 patients with meningiomas and 1,657 patients with gliomas were identified
      in the Swedish Cancer Registry. For every woman diagnosed with brain tumor, 5 age
      matched controls were selected among those in the Fertility Registry. Relative
      risks were estimated by odds ratios from conditional logistic regression. Ever
      parous women were at a reduced risk of glioma compared to nulliparous women,
      while parity was unrelated to meningioma risk. Age at first birth was unrelated
      to both meningioma and glioma risk. The gradient in risk between ever-parous and
      nulliparous women for gliomas, but not meningiomas, is difficult to explain
      biologically. A possible explanation is that pregnancy-induced alterations in
      androgen levels reduce the risk of glioma in parous women. Alternatively,
      childlessness may represent a marker of an occult glioma, negatively affecting
      fecundity. Overall, our present results do not support the notion that hormonal
      changes, or other physiological changes induced by childbearing, play an
      important role in the development of brain tumors.

PMID- 9247279
TI  - Lack of correlation between EBV serology and presence of EBV in the Hodgkin and
      Reed-Sternberg cells of patients with Hodgkin's disease.
AB  - Epstein-Barr virus (EBV) is detected in Hodgkin and Reed-Sternberg (HRS) cells in
      up to 50% of patients with Hodgkin's disease (HD). HD patients have been reported
      to express high serum titers against EBV antigens, even prior to the diagnosis of
      HD. Patients with high serum titers have a poorer prognosis. The aim of this
      study was to examine the relationship between the presence of EBV in HRS cells
      and the antibody titers reactive with different EBV antigens. Frozen serum and
      histopathological tissues were available from 107 untreated HD patients diagnosed
      between 1979 and 1991. The presence of EBV in the HRS cells was evaluated with
      immunohistochemistry directed against the LMP-1 antigen and/or with in situ
      hybridization of EBER-1. Analyses were performed of serum titers against early
      antigen (EA), diffuse (IgA and IgG) and restricted (IgG), virus-capsid antigen
      (VCA) (IgA and IgG), and EBV-encoded nuclear antigens (EBNA, EBNA 1, EBNA 2A,
      EBNA 2B, EBNA 6). EBV was detected in 27/107 (25%) tumor specimens, with a higher
      proportion in the MC group 8/13 (62%) (p < 0.01). IgG VCA and EBNA were detected
      in 99/107 (93%), evidence of a previous EBV infection. There were no significant
      relationships between antibody titers reactive with different EBV antigens and
      detectable EBV in HRS cells. Furthermore, there did not appear to be any
      relationship between EBV serology or the presence of EBV in HRS cells and
      clinical outcome. The role of EBV in the development of HD, especially its
      relationship to the immunological response, remains unclear.

PMID- 9247280
TI  - Interleukin-10 expression and cytotoxic-T-cell response in Epstein-Barr-virus
      associated nasopharyngeal carcinoma.
AB  - Interleukin-10 (IL-10) is an inhibitory cytokine produced by various cell types.
      It exhibits strong sequence homology to BCRF-1 (viral IL-10, vIL-10), an open
      reading frame in the Epstein-Barr-virus (EBV) genome. Using in situ hybridization
      (ISH), polymerase chain reaction (PCR) and immunohistochemistry, we checked 41
      cases of nasopharyngeal carcinoma (NPC), to study the presence of EBV in the
      tumor cells, as well as to clarify the relationship between IL-10 expression of
      the tumor cells and the response of cytotoxic T cells. IL-10 expression was
      studied by immunohistochemistry; as a result, 29 of 41 cases expressed EBER-1 RNA
      of EBV by ISH. In addition, 19 of the 29 with EBV and 9 of 12 without EBV cases
      expressed IL-10 in the tumor cells. The number of cytotoxic T cells increased in
      the tumor tissue, and the increase in the intratumoral stroma was stronger than
      in the remaining normal epithelia. The number of cytotoxic T cells also
      significantly increased in the cases with EBV. On the other hand, in the IL-10
      positive series, the number of cytotoxic T cells decreased significantly more
      than in IL-10-negative series. In view of the established inhibitory effects of
      IL-10, expression of IL-10 may therefore be one of the mechanisms for NPC cells
      as well as EBV to counter local immune defense. However, we could not conclude
      whether or not IL-10 expression was directly induced by EBV.

PMID- 9247281
TI  - Dominant TCRB-V-J chain usage and clonal expansion of sarcoma-reactive CD4+ HLA
      DR-restricted T cells suggest a limited set of immunodominant sarcoma antigens.
AB  - Tumor-reactive CD4+ T cells have been isolated from tumor patients, and their
      specifity but not T-cell receptor (TCR) repertoire has been analyzed. Since we
      have described CD4+ sarcoma-reactive T-cell clones, we now sought to determine
      whether the TCR repertoire of these clones provides information on the spectrum
      of recognized sarcoma antigens. We analyzed the TCR beta (TCRB) chain repertoire
      of 19 CD4+ HLA-DR-restricted T-cell clones reactive with the autologous sarcoma
      cell line MZ-MES-1, with HLA-DR-matched tumor cell lines of different tissue
      origins and B-cell blasts. We identified 7 different clonotypes, which used a
      limited set of TCRBV and TCRBJ segments. Although the CDR3 of the different
      clonotypes was diverse, repeated restimulation with sarcoma cells led to a
      monoclonal expansion of T cells with particular TCR clonotypes in 5/6 mixed
      lymphocyte tumor cell cultures (MLTC). One clonotype was found in 2 independent
      MLTC experiments. Sarcoma-reactive T cells were demonstrated in patient tumor
      infiltrating lymphocytes (TIL) and peripheral blood mononuclear cells (PBMC) by
      clonotypic PCR. Our results indicate a limited number of immunodominant antigens
      expressed by the sarcoma cells. The junctional diversity of the TCR clonotypes
      shows that these antigens did not lead to extensive negative thymic selection as
      classical autoantigens would have. Therefore, the recognized antigens might
      represent cryptic autoantigens related to cellular transformation or
      proliferation.

PMID- 9247282
TI  - Detection of pancreatic and gastric cancer cells in peripheral and portal blood
      by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain
      reaction.
AB  - Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19
      mRNA was applied to detect circulating cancer cells in the peripheral and portal
      blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was
      studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in
      peripheral and/or portal blood samples from patients with pancreatic cancer
      (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric
      cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n
      = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50
      healthy volunteers served as controls. RT-PCR was conducted in duplicate in each
      sample, and only samples showing keratin 19 transcript in both determinations
      were considered as being positive. All the pancreatic and gastric cancers, but
      none of the control blood samples, were found to be positive. Dilution study
      using pancreatic cancer cells serially mixed against peripheral blood showed that
      detection sensitivity was more than one cancer cell in 10(6) peripheral blood
      mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal
      blood samples gave positive results in one stage III and one stage IV patient,
      and that of peripheral blood samples gave positive results in 2 stage IV
      patients. No positive results were obtained in any of the blood samples from
      gastric cancer patients. Our results indicate that incidence of circulating
      cancer cells is unexpectedly very low even in advanced pancreatic and gastric
      cancer patients.

PMID- 9247283
TI  - Distinct manifestations of human papillomaviruses in the vagina.
AB  - To clarify the pathogenic relationships between human papillomavirus (HPV) and
      vaginal intraepithelial neoplasia (VAIN), we examined 71 vaginal biopsy specimens
      by histopathology and immunohistochemistry and analyzed the presence of HPV DNA
      by blot hybridization at Tm - 40 degrees C using an HPV 58 probe (PBM-58 method).
      We found 27 cases of VAIN in patients with previous hysterectomy or antecedent or
      concomitant cervical intraepithelial neoplasia (CIN) and 44 cases of VAIN in
      patients without any abnormal findings on the cervix and the vulva.
      Histopathologically, 53 of 71 cases were graded as VAIN I and 15 and 3 cases were
      VAIN II and III, respectively, while 59 cases showed positivity for HPV capsid
      antigen by immunohistochemistry. Using the PBM-58 method, all 71 VAIN cases
      harbored a single HPV type at more than 1,000 viral copies per cell. We
      identified 15 different types (HPV 16, 18, 30, 31, 35, 40, 42, 43, 51, 52, 53,
      54, 56, 58 and 66). Furthermore, we molecularly cloned 7 novel prototypes (HPV
      59, 61, 62, 64, 67, 69 and 71) from VAIN I. Our results are strongly indicative
      that HPVs are etiologic agents of VAIN, like in the case of CIN. The distinct
      manifestations of HPV infection in the vagina are discussed in comparison with
      those in the cervix.

PMID- 9247284
TI  - ELISA for complexes between urokinase-type plasminogen activator and its receptor
      in lung cancer tissue extracts.
AB  - A sandwich-type ELISA has been developed for the assessment of complexes between
      urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of
      squamous cell lung carcinomas. The assay is based on a combination of rabbit
      polyclonal anti-uPA antibodies and a biotinylated mouse anti-uPAR monoclonal
      antibody (MAb). The detection limit of the assay is approximately 0.5 fmol/ml. A
      linear dose-response is obtained with up to 40 fmol/ml of uPA:uPAR complexes,
      while uPA and uPAR separately do not cause any response in the ELISA. A buffer
      which has been used previously for optimal extraction of uPAR yields the highest
      amounts of uPA:uPAR complexes. Absorption of tumor extracts with anti-uPA or anti
      uPAR MAbs results in a complete disappearance of the ELISA signal, demonstrating
      the specificity of the ELISA. The recovery of chemically cross-linked uPA:uPAR
      complexes added to tumor extracts varies between 80% and 105%. The intra- and
      inter-assay variation coefficients are 5.3% and 9.8%, respectively. Furthermore,
      a peptide antagonist for uPAR was employed to evaluate de novo uPA:uPAR complex
      formation during tumor tissue extraction and the immunoassay procedure. Our
      results strongly indicate that de novo complex formation is a major factor to
      consider and that complexes analyzed in the presence of this antagonist represent
      original uPA:uPAR complexes present prior to tumor tissue processing. The present
      ELISA appears suitable for studying the potential prognostic impact of uPA:uPAR
      complexes in lung tumor tissue as well as other types of cancer.

PMID- 9247285
TI  - Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with
      renal-cell carcinoma.
AB  - We investigated the possible causative role of interleukin 6 (IL-6) in the
      paraneoplastic inflammatory syndrome and in paraneoplastic cholestasis (Stauffer
      syndrome) associated with renal-cell carcinoma in a series of 119 patients with
      metastases. IL-6 levels were found significantly higher in patients with
      paraneoplastic fever and weight loss. Patients with detectable serum IL-6 (n =
      90, 76%) had significantly higher serum CRP, haptoglobin, and serum alkaline
      phosphatase and gammaglutamyl-transferase levels. Platelets, polymorphonuclear
      neutrophil (PMN) and monocyte counts were also significantly higher in patients
      with detectable serum IL-6; in contrast, hemoglobin levels were significantly
      lower in patients with serum IL-6 over 80 pg/ml. Three of these patients were
      included in a phase-II trial of an anti-IL-6 monoclonal antibody given daily
      during 21 days. Reductions of CRP, haptoglobin and serum alkalin phosphatases
      were observed in all 3 patients during anti-IL-6 administration, with a
      subsequent increase up to or above pre-treatment levels after the end of anti-IL
      6. Decrease of platelets, PMN and monocyte counts were also observed in the 3
      patients during anti-IL-6 administration, with a normalization of cell counts in
      a patient with increased platelets, PMN and monocyte counts. Hemoglobin
      concentration, serum albumin concentration and lymphocyte counts remained stable
      in the 3 patients during and after anti-IL-6 administration. Serum IL-6, as
      evaluated by IRMA, decreased in the 3 patients during anti-IL-6 administration,
      but increased above pre-treatment levels after the end of anti-IL-6
      administration. These results demonstrate that IL-6 is involved in the
      physiopathology of paraneoplastic syndromes observed in patients with metastatic
      renal-cell carcinoma, in particular CRP and haptoglobin increase, paraneoplastic
      cholestasis, also paraneoplastic thrombocytosis, neutrophilia and monocytosis.

PMID- 9247286
TI  - Analysis of T-cell immune response in renal cell carcinoma: polarization to type
      1-like differentiation pattern, clonal T-cell expansion and tumor-specific
      cytotoxicity.
AB  - We assessed the naturally occurring T-cell immune response in primary renal cell
      carcinoma (RCC) tumors from 12 unselected patients. A predominance of CD3+ T-cell
      receptor (TCR)alpha/beta+ T cells was observed in tumor-infiltrating lymphocytes
      (TILs), in contrast with peripheral blood lymphopenia found in some patients.
      Activation antigen expression on TILs revealed an imbalance in the activation
      status, with a significant percentage of CD69+ and HLA-DR+ and a low percentage
      of CD25+ and CD71+ TILs. The lymphocyte activation gene-3 (LAG-3) was detected in
      some TIL subpopulations and especially in one patient in whom TILs were
      predominantly TCR alpha/beta+CD8+DR+LAG-3+. In addition, we found that RCC TILs
      are polarized to a global type 1-like (Th1/Tc1) differentiation pattern (strong
      secretion of interferon-gamma and interleukin-2 (IL-2) following CD3/TCR
      crosslinking) but are under the influence of the down-modulatory cytokines IL-6
      (secreted by tumor cells) and IL-10, within the tumor microenvironment. In 3 of 5
      patients, clonal T-cell expansion at the tumor site was found for several Vbeta
      specificities, suggesting that in situ stimulation of specific clonotypes in
      response to potential tumor antigens is a frequent event in RCC. Furthermore, in
      one patient, selective intratumor amplification of a Vbeta1 subpopulation (5% of
      TCR alpha/beta+ cells) corresponding to 2 distinct Vbeta1-Jbeta1.6 and Vbeta1
      Jbeta2.3 tumor-specific MHC class I-restricted cytotoxic T lymphocytes supports
      the view that discrete T-cell subsets contribute readily to in situ
      immunosurveillance.

PMID- 9247287
TI  - Expression of matrilysin in vascular endothelial cells adjacent to matrilysin
      producing tumors.
AB  - Matrilysin is believed to play important roles in tumor progression and
      metastasis. In the present study, we analyzed matrilysin-producing cells in
      various human cancer tissues by immunohistochemistry and in situ hybridization.
      Tumor cells in colorectal carcinomas, pancreatic carcinomas, transitional-cell
      carcinomas of the kidney and small-cell lung carcinomas were frequently positive
      for matrilysin. In addition, we found that endothelial cells of arterioles and
      venules adjacent to matrilysin-positive tumors expressed matrilysin mRNA and
      protein. The endothelial cells adjacent to matrilysin-negative tumors and those
      in normal tissues were negative for matrilysin. Furthermore, analyses by casein
      zymography, Western blotting and RT-PCR showed that matrilysin was weakly
      expressed by cultured human umbilical vein endothelial cells. Our results suggest
      that the expression of matrilysin in vascular endothelial cells and in tumor
      cells may be regulated by common soluble factors, and that endothelial cell
      derived matrilysin may contribute to tumor angiogenesis and tumor metastasis.

PMID- 9247288
TI  - Human papillomavirus (HPV) in an Icelandic population: the role of HPV DNA
      testing based on hybrid capture and PCR assays among women with screen-detected
      abnormal Pap smears.
AB  - This study was based on 358 cases with abnormal smears referred for colposcopy
      and HPV DNA testing. We analysed: 1) the frequency of different grades of cyto-
      and histopathologic findings; 2) the frequency and relative amount of HPV DNA
      with the hybrid capture assay (HCA) in swabs, and the frequency of HPV with PCR
      in swabs (-S) and biopsies (-B); and 3) the frequency of HPV types according to
      the grade of the cyto- and histopathologic findings. Of all cases, 95% were
      positive with all HPV tests combined. The HCA (HPV: 16, 18, 31, 33, 35, 45, 51,
      52 and 56) and the PCR-S and PCR-B (HPV: 16, 18, 31, 33 and 35) tests for high
      risk HPV exhibited sensitivities of 57%, 56% and 48%, respectively. The high
      grade smears and the high-risk PCR-S HPV had about 80% sensitivity for histologic
      high-grade lesions compared with around 70% for HCA and the PCR-B. Combining the
      high-grade smears and the high-risk HPV increased the sensitivity to 93-96%.
      Among the cervical intraepithelial neoplasia I (CIN I) and the atypical squamous
      cells of undetermined significance (ASCUS) smears the sensitivity of high-risk
      HPV for high-grade histologic lesions was 63% for the HCA and 79% for the PCR-S.
      No correlation was found between the relative amount of HPV DNA detected by HCA
      and the grade of cyto- and histological lesions. We conclude that the results
      strongly indicate that HCA is less sensitive than PCR in the diagnosis of high
      risk HPV, that swabs are more sensitive than biopsies as a sampling method, that
      high-risk HPV and high-grade smears are complementary for the diagnosis of high
      grade histologic lesions and that the present role of HPV testing in screening
      could be limited to identifying women with low-grade smears and koilocytotic or
      low-grade colposcopic biopsies that are at risk of concealing or developing high
      grade histologic lesions.

PMID- 9247290
TI  - Expression of mucin-associated tumor antigens is altered by cell density.
AB  - Mucin-associated sialylated Lewis antigens are implicated in tumor cell
      metastasis and are used in several tests for pancreatic cancer. Despite their
      clinical importance, little is known about the structures of the oligosaccharides
      of pancreatic cancer mucins or about the regulation of their synthesis or of the
      synthesis of their protein cores. In this study, we examined the effects of
      culture at high cell density on the expression of these antigens in the SW1990
      human pancreatic cancer cell line. Mucins from cells that were 2.5 weeks post
      confluent had increased expression of sialyl-Lewis(a) and Lewis(x) antigens but
      reduced expression of the DU-PAN-2 antigen (NeuAc alpha2,3Galbeta1,3GlcNAc-Gal-R)
      when compared to mucins from 1 day post-confluent cells. Sialyl-Lewis antigens
      differ from the DU-PAN-2 antigen by the presence of an additional fucose. Mucins
      from 2.5-week cells also had increased binding to lectins specific for fucose,
      such as AAL and UEAI, with no apparent change in the binding of lectins specific
      for sialic acids. Metabolically radiolabeled O-linked oligosaccharides with
      sialyl-Lewis(a) antigenic reactivity eluted from Bio-Gel P-10 in the region of
      sialylated and sulfated oligosaccharides. Oligosaccharides eluted from QAE
      Sephadex (2 mM Tris base) in a pattern suggesting the presence of 1, 2 and 3 or
      more negative charges per oligosaccharide. Even after desialylation and
      desulfation, oligosaccharides eluted from Bio-Gel P-10 with apparent molecular
      sizes greater than glucose oligomers of 12 units. Culture of SW 1990 cells at
      high density also increased the steady-state levels of mRNA for mucins MUC1, 2,
      4, 5 and 6. In summary, after prolonged culture at high cell density, SW1990
      cells have qualitative changes in their oligosaccharides that may be due to up
      regulation of fucosyltransferases.

PMID- 9247289
TI  - Country-specific constancy by age in cagA+ proportion of Helicobacter pylori
      infections.
AB  - Helicobacter pylori strains may be either cagA+ or cagA-, and in logitudinal
      studies, infection with a cagA+ strain has been associated with increased risk
      for the development of atrophic gastritis and cancer of the distal stomach. We
      sought to determine the relative proportion of strains producing CagA in
      different geographic locales, and the extent to which CagA seroprevalence varied
      in countries with different gastric and esophageal cancer rates. Using an enzyme
      linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera
      from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China,
      Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA
      seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each
      substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch
      (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were
      relatively constant across gender and age groups. Reported gastric but not
      esophageal cancer rates for the 8 studied populations were significantly
      associated with H. pylori seroprevalence. Variation in CagA positivity rates was
      not significantly associated with variation in either gastric or esophageal
      cancer rates. Our data suggest that CagA seroprevalence is not the major factor
      influencing gastric cancer rates.

PMID- 9247291
TI  - Changes in the subunit distribution of prosomes (MCP-proteasomes) during the
      differentiation of human leukemic cells.
AB  - The subunit composition of cell-internal and surface prosomes during phorbol
      myristate acetate (PMA)-induced differentiation of human leukemic T lymphocytes
      (CCRF-CEM cell line) was studied in relation to clusters of differentiation (CD)
      markers. PMA inhibited cell growth and decreased the amounts of CD1a and CD4
      while CD3, CD8, CD25, CD45, CD57 and MHCI increased it; the p53 anti-oncogene
      increased while actin levels remained constant. Cells incubated with the inducer
      PMA for 3 days and placed in fresh inhibitor-free medium resumed growth at a low
      rate, while the CD values slowly reverted to those of the initial phenotype. The
      presence and relative amounts of prosome subunits were analyzed by flow
      cytometry, light and fluorescent microscopy and Western blotting using 3
      monoclonal antibodies (p25K, p27K and p30-33K MAbs). The decrease in cytoplasmic
      antigens on day 3 was remarkable (cells followed for 7 days) while increased
      surface antigens were observed. Changes in the subcellular distributions of
      prosome antigens, particularly the p25K and p30-33K subunit, were correlated with
      a partial arrest of the cell cycle. Interestingly, the composition of cell
      internal and surface prosomes showed different patterns of change.

PMID- 9247292
TI  - Selection of radioimmunoconjugates for the therapy of well-established or
      micrometastatic colon carcinoma.
AB  - In order to optimize radioimmunotherapy (RAIT) as a cancer-treatment modality, it
      is necessary to select the appropriate radionuclide and antibody carrier. We
      evaluated the therapeutic potential of a single cycle of Mu-9 anti-CSAp
      monoclonal antibody (MAb) labeled with 3 different radionuclides, 131I, 90Y and
      188Re. Intact antibodies and bivalent fragments with different blood clearance
      kinetics, normal organ distribution and varying tumor accretion and retention are
      also evaluated. Efficacy of treatment for large and small tumor burden was
      assessed in nude mice bearing s.c. GW-39 human colonic-carcinoma xenografts or
      intrapulmonary micrometastatic GW-39 colonies at the maximal tolerated dose of
      each agent. The magnitude and duration of myelosuppression associated with each
      radioantibody was considered by monitoring peripheral blood counts, marrow colony
      forming unit activity and hematopoietic tissue weight. Radiation-dose estimates
      were calculated based on the kinetics of antibody accretion and elimination from
      tumor and normal tissues, and the results were correlated with tumoricidal
      activity and dose-limiting toxicity results. These studies, therefore, represent
      a detailed analysis, in a well-defined experimental tumor system, of several
      parameters (antibody form, radioisotope, tumor size) influencing the overall
      outcome of RAIT using equitoxic doses. It was found that myelosuppression is the
      primary dose-limiting toxicity for all radioantibodies except 90Y-F(ab')2, even
      though the different agents showed varied organ distribution. In a single-cycle
      treatment schedule of Mu-9 MAb, the 131I-labeled IgG is the radioimmunoconjugate
      of choice for the treatment of s.c. and intrapulmonary growth of the GW-39 human
      colonic-carcinoma xenograft in nude mice.

PMID- 9247293
TI  - MIBG causes oxidative stress and up-regulation of anti-oxidant enzymes in the
      human neuroblastoma cell line SK-N-BE(2c).
AB  - We report the effects of meta-iodobenzylguanidine (MIBG), a neuroblastoma-seeking
      agent, on cell proliferation and several oxidative stress-related parameters in
      the human neuroblastoma cell line SK-N-BE(2c). MIBG inhibited the proliferation
      of this cell line in micromolar concentrations. Measurements of the
      malondialdehyde (MDA) concentrations (a measure of the extent of lipid
      peroxidation) of cells treated with MIBG showed that increasing concentrations of
      MIBG led to an increase in MDA levels of the cells. This effect was most
      pronounced after one day of cellular exposure to MIBG and disappeared after 3
      days. Disappearance of the elevated MDA levels caused by MIBG is probably the
      result of increased activity of the H2O2 detoxifying enzymes, catalase and
      glutathion peroxidase (GPx). The catalase- and GPx-enzyme activity of cells
      exposed to MIBG steadily increased with time, reaching a maximum after 4 days.
      Oxidative stress caused by MIBG thus at first leads to cellular damage (lipid
      peroxidation) but over a longer period does not lead to decreased proliferation
      rate of the cells, most likely because of cellular adaptation to increased
      oxidative stress by up-regulation of the H2O2 detoxifying enzymes catalase and
      GPx.

PMID- 9247294
TI  - 5-methylcytosine is present in the 5' flanking region of Ha-ras in mouse liver
      and increases with ageing.
AB  - Modifications to DNA-5-methylcytosine (5MeC) content (i.e., alterations in the
      level of 5MeC) constitute epigenetic events. In general, hypomethylation of a
      gene is necessary but not sufficient for expression, while methylated genes
      typically are quiescent. Ha-ras is an oncogene commonly implicated in murine
      liver tumorigenesis, often, though not always, involving mutation. A PCR-based
      approach using pre-PCR digestion with methylation-sensitive enzymes was employed
      to determine the 5MeC content of the 5' flanking region of this gene in (i)
      B6C3F1 and C57BL/6 mouse liver from young animals (4 months old) and (ii) B6C3F1
      mouse liver from aged animals (24 months old). Two segments of the 5' flanking
      region of Ha-ras were examined. We demonstrate the presence of 5MeC in a portion
      of the 5' flanking region of Ha-ras that does not share characteristics of a CpG
      island, while a region that shares CpG island characteristics is primarily
      unmethylated. Differences in methylation status in these areas of Ha-ras were not
      observed between B6C3F1 and C57BL/6 mouse livers. Increases in methylation status
      were observed with ageing in B6C3F1 mouse liver. These data provide a role for
      methylation in regulating Ha-ras expression in mouse liver. Ha-ras in human liver
      has been reported to be unmethylated. There are substantial sequence differences
      in a key region of the 5' flanking region of Ha-ras in mice as compared to
      humans. These differences in DNA methylation and sequence may, in part, provide a
      basis for the frequent involvement of Ha-ras in mouse liver tumors and its
      virtual lack of involvement in human tumors.

PMID- 9247295
TI  - Bombesin stimulates the motility of human prostate-carcinoma cells through
      tyrosine phosphorylation of focal adhesion kinase and of integrin-associated
      proteins.
AB  - Bombesin-like peptides, including the mammalian homologue gastrin-releasing
      peptides, are highly expressed and secreted by neuroendocrine cells in prostate
      carcinoma (PCa) tissues and are likely to be related to the progression of this
      disease. In the present study, we show that bombesin enhances the migration of
      androgen-independent PCa cells (PC-3) in vitro, while not affecting their
      adhesion to extracellular matrix proteins. The bombesin-increased motility of PC
      3 cells occurs through its receptor, and, as shown with inhibitors, it likely
      requires activation of both protein tyrosine kinases (PTKs) and protein kinases C
      (PKCs). Because the focal adhesion kinase pp125FAK plays a key role in
      adhesion/motility and is highly expressed in advanced PCa, we examined whether in
      PC-3 cells bombesin signal transduction triggers the tyrosine phosphorylation of
      this PTK and of associated integrins and signaling proteins likely to be present
      in focal adhesion plaques. pp125FAK tyrosine phosphorylation was stimulated by
      bombesin and mimicked by PKC activation with the tumor-promotor phorbol 12
      myristate-13-acetate (PMA). Moreover, this effect of bombesin on pp125FAK
      tyrosine phosphorylation requires the presence of both active PKC and
      cytoskeleton integrity since this signal was abolished by down-regulating PKCs
      induced by prolonged PMA treatment or by PKC inhibition with GF 109203X, as well
      as by disruption of the cytoskeleton with cytochalasin D. We also show that
      bombesin increases the tyrosine phosphorylation of a 95-kDa protein (pp95) which
      was co-immunoprecipitated with the alpha v and beta (3 and 5) subunits, forming
      integrin receptors with alpha v in PC-3 cells. The protein pp95 is distinct from
      the endogenously tyrosine-phosphorylated beta3 subunit. In addition, upon
      bombesin treatment, the beta1, beta3 and beta5 integrin subunits co
      immunoprecipitated with pp125FAK and major phosphotyrosine (pY)-containing
      proteins of 125 and 68-70 kDa, likely corresponding to pp125FAK and paxillin.
      Together our data suggest that, in addition to PKC activation, tyrosine
      phosphorylation of pp125FAK and integrin-associated proteins may play an
      important role in bombesin signaling, triggering the processes of PCa cell
      motility and invasion.

PMID- 9247296
TI  - Involvement of T-cell subsets and natural killer (NK) cells in the growth
      suppression of murine fibrosarcoma cells transfected with interleukin-12 (IL-12)
      genes.
AB  - A 3-methylcholanthrene-induced fibrosarcoma cell line of BALB/c origin, CMS5j,
      was co-transfected with cDNA for the p40 and p35 subunits of interleukin-12 (IL
      12). Injection of transfected cells producing 5 x 10(3) U IL-12/10(6)
      cells/ml/day in nude mice with an established fibrosarcoma at a contralateral
      site efficiently eliminated tumor growth in the early phase (injection on day 0
      or 4) but not later (day 8). This effect could be abrogated by simultaneous i.v.
      injection of antibodies against NK1.1 or ASGM1 (asialoGM1 = ganglio-N-tetraosyl
      ceramide), which indicates that natural killer (NK) cells play a major role in
      tumor eradication or suppression when stimulated by IL-12. In wild-type mice,
      application of IL-12-secreting CMS5j cells abrogated growth of tumors established
      8 days before but not earlier. Based on our experiments with antibody blocking in
      vivo, all CD4+, CD8+ and ASGM1+ cells are involved in tumor rejection. However,
      in our system, CD4+ cells or CD8+ cells alone, but not ASGM1+ cells alone, also
      could lead to tumor rejection. IL-12-engineered fibrosarcoma cells may constitute
      an efficient and safe system for immunotherapy of cancer.

PMID- 9247297
TI  - Amphiregulin antisense oligonucleotide inhibits the growth of T3M4 human
      pancreatic cancer cells and sensitizes the cells to EGF receptor-targeted
      therapy.
AB  - Human pancreatic cancers overexpress the epidermal growth factor (EGF) receptor
      (EGFR) and all 5 ligands that bind to this receptor, including amphiregulin. It
      is not known, however, whether amphiregulin contributes in an autocrine manner to
      enhance pancreatic cancer cell growth. Therefore, we used an amphiregulin
      antisense oligonucleotide (AR-AS) to suppress amphiregulin expression in T3M4
      human pancreatic cancer cells. These cells express high levels of EGFR and
      amphiregulin. AR-AS abolished amphiregulin immunoreactivity in T3M4 cells,
      decreased amphiregulin release into the medium and inhibited cell growth in a
      dose-dependent manner. Exogenous amphiregulin reversed AR-AS-mediated growth
      inhibition. A random oligonucleotide (AR-R) did not alter either cell growth or
      cellular amphiregulin immunoreactivity. AR-AS also increased cellular EGFR
      protein levels and enhanced the growth-inhibitory actions of TP40, a chimeric
      protein consisting of transforming growth factor-alpha coupled to Pseudomonas
      exotoxin that internalizes into cells via EGFR. These findings indicate that
      there is an important EGFR/ amphiregulin autocrine loop in T3M4 cells and raise
      the possibility that modalities aimed at abrogating amphiregulin action may prove
      useful in pancreatic cancer, especially when used in conjunction with EGFR
      targeted therapy.

PMID- 9247298
TI  - Polymerase chain reaction compared with dot blotting for the determination of N
      myc gene amplification in neuroblastoma.
AB  - The magnitude of N-myc amplification (NMA) influences the treatment strategy of
      localized neuroblastomas. Reliable assays are therefore needed for all types of
      tumor samples. The aim of this comparative study of 119 tumor samples was to
      determine whether a polymerase chain reaction (PCR)-based assay could replace the
      current dot blot assay as a routine and reliable means of determining NMA. The 2
      assays exhibited comparable sensitivity and were completely concordant for
      samples containing at least 20% neuroblastoma cells. In their present state, both
      assays remain semi-quantitative since an absolute quantification of the N-myc
      copy number in clinical samples is limited by uncertainty about the amplification
      level of reference cell lines and by the estimation of the proportion of
      malignant cells. However, PCR offers several advantages over dot blotting, such
      as feasibility on minute samples, simplicity, standardization, rapidity and cost
      effectiveness.

PMID- 9247299
TI  - Differential inhibitory effect of L-lysine on renal accumulation of 67Cu-labelled
      F(ab')2 fragments in mice.
AB  - The basic amino acid L-lysine was administered to mice in an attempt to
      circumvent unwanted renal accumulation of 67Cu-labelled F(ab')2 fragments derived
      from the anti-NCAM IgG1, SEN7 and anti-CEA IgG1 monoclonal antibody (MAb)35. In
      control experiments, significant renal uptake of both 67Cu-labelled F(ab')2
      fragments was observed, radiolabel being primarily localised to proximal tubules
      in the renal cortex. Following optimised L-lysine dosing protocols, renal uptake
      of 67Cu-MAb35 F(ab')2 was inhibited by up to 42%. Surprisingly, little inhibition
      (< 10%) of 67Cu-SEN7 F(ab')2 uptake was observed. Experiments to investigate this
      differential inhibition indicated that inhibition of MAb35 F(ab')2 uptake was
      relatively short-lived (approx. 6 hr), whilst no apparent differences were found
      in blood clearance rates between either 67Cu-F(ab')2 fragment. L-lysine
      administration caused a significant diuresis with high levels of intact 67Cu
      labelled SEN7 and MAb35 F(ab')2 appearing in the urine, possibly due to blockade
      of renal uptake and lysine-induced increases in glomerular membrane permeability.
      Iso-electric focusing studies failed to identify any charge differences between
      the 67Cu-labelled F(ab')2 fragments, although a cathodal migration of all 67Cu
      labelled samples, presumably due to the net positive charge conferred by addition
      of 67Cu2+ ions, was observed. Our results demonstrate that in addition to net
      charge, other unidentified characteristics may influence renal accumulation of
      radiometal-labelled F(ab')2 fragments and their inhibition by L-lysine.

PMID- 9247300
TI  - Malignant neoplasms in cyclosporin A-induced autoimmunity (CyA-AI).
AB  - Lethally X-irradiated LEW rats reconstituted with syngeneic bone marrow and given
      low-dose Cyclosporine A (CyA) for 5 weeks develop, after withdrawal of CyA,
      symptoms of disease resembling graft-vs.-host disease (GVHD) as seen after
      allogeneic bone-marrow transplantation. Symptoms of disease may include acute
      dermatitis and chronic disease resembling scleroderma. Since anti-class II MHC
      cytotoxic lymphocytes are generated in this model, it has been proposed as an
      anti-tumor regimen in humans. We now report that LEW rats treated according to
      this protocol may, after cessation of CyA administration, paradoxically develop
      malignant neoplasms. Of 48 experimental animals, 31 developed rapidly progressive
      subcutaneous and/or intracutaneous tumors commencing at 6 weeks, 13 weeks and 6
      months after cessation of CyA. Tumors were of mesenchymal origin, usually high
      grade sarcoma, adenocarcinoma or both mesenchymal and epithelial tumors. Such
      tumor incidence exceeded the incidence of tumor growth in X-irradiated controls,
      and in rats subjected to thymectomy prior to X-irradiation and CyA
      administration. CyA by itself induced no tumors. Our results show that total body
      X-irradiation is required for tumor development but that the presence of CyA
      induced autoimmune disease increases the incidence significantly.

PMID- 9247301
TI  - Modulation of resistance to anti-APO-1-induced apoptosis in osteosarcoma cells by
      cytokines.
AB  - The CD95/APO-1 Fas receptor/ligand system plays a crucial role in growth control
      by mediating apoptosis in lymphoid and non-lymphoid cells. To investigate the
      role of CD95-mediated apoptosis in osteosarcoma, we studied 3 human osteosarcoma
      cell lines (HOS/TE 85, MG 63 and Saos-2) and osteoblasts derived from bone
      biopsies. In contrast to osteoblast-like cells, all cell lines were resistant to
      anti-APO-1-induced apoptosis despite constitutive CD95 expression at intermediate
      levels. Blocking of macromolecular synthesis by cycloheximide or actinomycin D or
      modulation of CD95 expression by cytokines (TNF-alpha and/or gamma-interferon)
      restored sensitivity to anti-APO-1-induced cell death. PCR analysis of the CD95
      transcripts revealed the production of a truncated splice variant that codes for
      a soluble form of the CD95 receptor. Synthesis and secretion of soluble CD95
      protein into the culture supernatant was demonstrated by Western blot analysis.
      Treatment with sensitizing cytokines led to up-regulation of full-length CD95
      transcripts and the encoded membrane-bound CD95 protein but not the truncated
      mRNA splice variant and the corresponding soluble receptor, as shown by PCR and
      Western blot analysis. The biological activity of soluble CD95 secreted by
      osteosarcoma cells was demonstrated by the ability of osteosarcoma supernatants
      to protect the sensitive T-cell line Jurkat from anti-APO-1-mediated apoptosis.
      Our results suggest that the production of soluble CD95 by osteosarcoma cell
      lines that may block physiological death signals and the production of membrane
      bound CD95 are differently regulated by cytokines via modulation of RNA splicing.

PMID- 9247302
TI  - Constitutive expression of FGF2/bFGF in non-tumorigenic human prostatic
      epithelial cells results in the acquisition of a partial neoplastic phenotype.
AB  - Fibroblast growth factor 2 (FGF2), also known as basic fibroblast growth factor
      (bFGF), belongs to the FGF family, which consists of at least 9 closely related
      members. FGF2 is a potent mitogen for fibroblasts derived from normal prostate
      and, to a lesser extent, for prostatic epithelial cells. Its role in the
      physiology of the normal prostate seems to be limited to stromal cells, whereas
      in prostate cancer FGF2 may also have an autocrine/paracrine effect on epithelial
      cells. In order to better understand the effects of FGF2 on the prostatic
      epithelium, especially its role in the progression of prostate cancer by
      establishing an autocrine-stimulation loop, we transfected FGF2 cDNA into a human
      prostatic epithelial cell line, PNT1A, immortalized with SV40 large-T antigen.
      This cell line is non-tumorigenic and expresses a high-affinity FGF2 receptor,
      FGFR1/flg. We characterized 3 independent FGF2-transfected clones and found that
      the establishment of an FGF2 autocrine loop on these cells led to (i) serum
      independent growth, (ii) increased proliferation and (iii) anchorage-independent
      growth. Such results argue in favor of the possible action of FGF2 on progression
      of prostate cancer via an FGF2 autocrine loop on epithelial cells.

PMID- 9247303
TI  - Accumulation of p16INK4a in mouse fibroblasts as a function of replicative
      senescence and not of retinoblastoma gene status.
AB  - Viral transformation of mouse and human fibroblasts has very different effects on
      the composition of cyclin-dependent kinase (Cdk) complexes. In human cells
      transformed by the large T-antigen of simian virus 40 (SV40 T-Ag) and human
      tumour cell lines that lack a functional retinoblastoma gene product (pRb) no
      cyclin D1-Cdk4 complexes can be detected because all the available Cdk4 is
      associated with the Cdk-inhibitor p16INK4a. In contrast, SV40-transformed mouse
      cells and fibroblasts from Rh1-nullizygous mouse embryos contain normal levels of
      cyclin D1-Cdk4 complexes. To investigate this species difference, we have
      compared the biochemical properties and expression of mouse p16INK4a with that of
      its human counterpart. There is a marked increase in p16 RNA and protein levels
      as primary embryo fibroblasts approach their finite lifespan in culture, but
      mouse p16 expression does not appear to be influenced by the status of pRb.
      Transformed or spontaneously immortalized mouse cells therefore do not achieve
      the very high levels of p16 characteristic of pRb-negative human cell lines. We
      suggest that these differences may be related to the different frequencies with
      which mouse and human cells can be immortalized in culture.

PMID- 9247304
TI  - Induction of senescence in human malignant glioma cells by p16INK4A.
AB  - p16INK4A is a G1-specific cell cycle inhibitor which maps to human chromosome
      9p21, a region frequently mutated or deleted in cancer cell lines and primary
      tumors. In glioblastomas the frequency of homozygous deletions is 40-70% making
      it one of the most common mutations in this tumor type. We have analysed the
      significance of the loss of this gene in gliomas by introducing the cDNA for
      p16INK4A into the human glioma cell line U-1242 MG which has a deleted CDKN2
      locus. We used the tetracycline repressible vector system and obtained two stably
      transfected clones that expressed p16INK4A upon induction. p16INK4A expression
      caused a G1 arrest and enlargement of the cells similar to that of senescent
      cells. When staining for Senescence-Associated beta-galactosidase activity,
      described to be specific for senescent cells, we could show that the enlarged
      cells specifically gave a positive staining reaction. This senescence phenotype
      was dependent on the continuous expression of p16INK4A since it was reversed upon
      reintroduction of tetracycline suppression. Thus, the induced expression of
      p16INK4A in these glioma cells reverted their immortal phenotype and caused an
      immediate cellular senescence.

PMID- 9247305
TI  - Differential expression of p16INK4a and p16beta transcripts in B-lymphoblastoid
      cells from members of hereditary melanoma families without CDKN2A exon mutations.
AB  - Mutations in the CDKN2A (p16INK4a) tumour suppressor gene on chromosome 9p21 are
      associated with inherited predisposition to melanoma, yet some 9p-linking
      hereditary melanoma families show no mutations in this gene. Splicing of CDKN2A
      exons 2 and 3 to an alternative first exon produces a transcript (p16beta)
      encoding a protein with cell cycle regulatory properties. We have analysed allele
      specific expression levels of both the p16INK4a and p16beta transcripts in B
      lymphoblastoid cells from 18 members of hereditary melanoma kindreds including
      four unrelated control individuals. In 15 of the 18 individuals examined, steady
      state levels of each transcript either originated equally from each parental
      chromosome, or one parental chromosome was dominant for both transcripts.
      However, in three affected members of two 9p-linking hereditary melanoma
      kindreds, without exonic CDKN2A mutations, this pattern of coordinate expression
      was disrupted. In these individuals there was underexpression of the p16beta
      transcript, relative to the p16INK4a transcript, from the chromosome segregating
      with disease susceptibility. Loss of coordinate expression of the p16INK4a and
      p16beta transcripts may be an alternative genetic basis for melanoma
      susceptibility in certain 9p-linking kindreds.

PMID- 9247306
TI  - Effect of mutation of cytoplasmic receptor domain and of genistein on transport
      of acidic fibroblast growth factor into cells.
AB  - Acidic fibroblast growth factor (aFGF) binds to specific transmembrane receptors
      and is partly transported to a nuclear location. To study this transport we made
      a kinase-negative mutant of FGF receptor 4 as well as one where the major part of
      the cytoplasmic receptor domain was deleted, and expressed them in U2OSDr1 cells
      that lack functional FGF receptors. All receptors mediated endocytic uptake of
      aFGF. Translocation of the growth factor across cellular membranes was assayed
      using aFGF with a C-terminal CAAX-motif, which signals addition of a farnesyl
      group onto the protein once in the cytosol. CAAX-tagged aFGF was farnesylated
      when incubated with cells containing wild-type or kinase-negative receptors. It
      was not farnesylated in cells expressing the deleted receptor, or when the
      incubation was in the presence of genistein. aFGF incubated with cells
      transfected with wild-type or kinase-negative receptors, but not with the deleted
      receptor, was partly recovered from the nuclear fraction in the absence, but not
      in the presence of genistein. The data indicate that the cytoplasmic receptor
      domain, but not the active kinase, is required for transport of the growth factor
      into cells, and that genistein inhibits the process.

PMID- 9247307
TI  - The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in
      human breast and ovarian cancer cells.
AB  - Recent studies indicate that oncogenes may be involved in determining the
      sensitivity of human cancers to chemotherapeutic agents. To define the effect of
      HER-2/neu oncogene overexpression on sensitivity to chemotherapeutic drugs, a
      full-length, human HER-2/neu cDNA was introduced into human breast and ovarian
      cancer cells. In vitro dose-response curves following exposure to 7 different
      classes of chemotherapeutic agents were compared for HER-2- and control
      transfected cells. Chemosensitivity was also tested in vivo for HER-2- and
      control-transfected human breast and ovarian cancer xenografts in athymic mice.
      These studies indicate that HER-2/neu overexpression was not sufficient to induce
      intrinsic, pleomorphic drug resistance. Furthermore, changes in chemosensitivity
      profiles resulting from HER-2/neu transfection observed in vitro were cell line
      specific. In vivo, HER-2/neu-overexpressing breast and ovarian cancer xenografts
      were responsive to different classes of chemotherapeutic drugs compared to
      control-treated xenografts with no statistically significant differences between
      HER-2/neu-overexpressing and nonoverexpressing xenografts. We found no instance
      in which HER-2/neu-overexpressing xenografts were rendered more sensitive to
      chemotherapeutic drugs in vivo. HER-2/neu-overexpressing xenografts consistently
      exhibited more rapid regrowth than control xenografts following initial response
      to chemotherapy suggesting that a high rate of tumor cell proliferation rather
      than intrinsic drug resistance may be responsible for the adverse prognosis
      associated with HER-2/neu overexpression in human cancers.

PMID- 9247308
TI  - Structure and expression pattern of human ALR, a novel gene with strong homology
      to ALL-1 involved in acute leukemia and to Drosophila trithorax.
AB  - The ALL-1 gene is involved in human acute leukemia through chromosome
      translocations or internal rearrangements. ALL-1 is the human homologue of
      Drosophila trithorax. The latter is a member of the trithorax group (trx-G) genes
      which together with the Polycomb group (Pc-G) genes act as positive and negative
      regulators, respectively, to determine the body structure of Drosophila. We have
      cloned a novel human gene, ALR, which encodes a gigantic 5262 amino acid long
      protein containing a SET domain, five PHD fingers, potential zinc fingers, and a
      very long run of glutamines interrupted by hydrophobic residues, mostly leucine.
      The SET motif, PDH fingers, zinc fingers and two other regions are most similar
      to domains of ALL-1 and TRX. The first two motifs are also found in other trx-G
      and Pc-G proteins. The ALR gene was mapped to chromosome band 12q12-13, adjacent
      to the VDR gene. This region is involved in duplications and translocations
      associated with cancer. The analysis of ALR expression showed that its
      approximately 18 kb long mRNA is expressed, like ALL-1, in most adult tissues,
      including a variety of hematopoietic cells, with the exception of the liver.
      Whole mount in situ hybridization to early mouse embryos indicates expression in
      multiple tissues. Based on similarities in structure and expression pattern, ALR
      is likely to play a similar role to ALL-1 and trx, although its target genes have
      yet to be identified.

PMID- 9247309
TI  - Heat shock induces transient p53-dependent cell cycle arrest at G1/S.
AB  - Heat shock (43 degrees C, 45 min) induced transient nuclear accumulation of p53
      in primary human fibroblasts without any clonogenically toxic effects. The
      accumulation of p53 reached a maximal level 3 approximately 5 h after heat shock,
      and returned to the basal level within 12 h. Following the increase in p53 level,
      cell cycle arrest at G1/S was observed in normal fibroblasts, whereas neither
      nuclear accumulation of p53 nor cell cycle arrest were observed in HeLa cells. By
      comparing cell cycle patterns of heat-treated mouse cells with different
      genotypes at the p53 locus (+/+, +/-, -/-), the observed cell cycle arrest at
      G1/S was demonstrated to be p53-dependent. Cell cycle arrest in normal human
      fibroblasts continued for nearly 24 h, resulting in a one day delay of cell
      growth compared with non-treated cells. Following enhancement of the p53 level,
      the amount of p21/WAF1/ CIP1 increased, and the high level of p21 was sustained
      for almost one day in a cell cycle-independent manner, suggesting the involvement
      of p21 in the inhibition of cell cycle progression by heat shock.

PMID- 9247310
TI  - Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth
      inhibition and differentiation of B16-F10.9 tumor cells.
AB  - Interleukin-6 (IL-6) inhibits the growth of melanocytes and of early stage
      melanoma cells, but not that of advanced melanoma cells. The in vitro IL-6
      response can be restored in the highly metastatic melanoma B16-F10.9 by addition
      of recombinant soluble IL-6 receptor alpha-chain (sIL-6R). The F10.9 cells then
      undergo irreversible growth-arrest and show increased adherence with changes from
      epithelioid to spindleoid morphology. The sIL-6R is required for IL-6 to induce a
      sustained activation of the various Stat transcription factors which bind to
      specific IL-6 inducible enhancers. The sIL-6R and IL-6 combination causes an
      increase in the level of the anti-oncogenic transcription factor IRF-1 protein
      and DNA-binding, which remain elevated for 24 h. The promoter activity of the
      anti-oncogenic p21/Waf-1/Cip-1 gene is induced and accumulation of the p21
      protein is observed. These results illustrate the potent agonist activity of sIL
      6R on molecular pathways which could mediate the growth-arrest and
      differentiation of the metastatic melanoma cells. Previously observed
      antimetastatic effects of IL-6 therapy in mice bearing F10.9 tumors may be at
      least partly due to direct growth inhibition and differentiation elicited by sIL
      6R present in biological fluids.

PMID- 9247311
TI  - Detection of the proto-oncogene eIF4E in surgical margins may predict recurrence
      in head and neck cancer.
AB  - Head and neck squamous cell cancers (HNSCC) have a high local recurrence rate due
      to incomplete tumor resection. The use of molecular markers to establish surgical
      margins may decrease local recurrence. Surgical margins are determined by
      histopathologic analysis on frozen sections. We postulate that genetic and
      molecular changes precede gross histologic alterations. Tumor markers may improve
      the reliability of pathology examination, but those evaluated to date lack the
      sensitivity needed for routine clinical use. Western blot analysis showed
      elevated eIF4E in all 26 HNSCC in contrast to its low expression in benign
      lesions. Surgical margins were analysed for eIF4E in 23 patients. Twelve patients
      showed elevated eIF4E in histologically negative margins. Cancer has recurred in
      5 of the 12 patients as opposed to none of the 11 patients with eIF4E negative
      margins (P= 0.02, Log rank test). This is the first report of eIF4E in HNSCC, as
      a sensitive and specific marker for HNSCC, with potential for defining clear
      resection margins. The correlation between elevated levels of eIF4E at the
      margins and recurrence highlights its ability to detect malignant cells prior to
      clear-cut alterations in morphology. The accuracy and simplicity of these assays
      underscore the usefulness of eIF4E in managing HNSCC.

PMID- 9247312
TI  - PLC-gamma activation is required for PDGF-betaR-mediated mitogenesis and
      monocytic differentiation of myeloid progenitor cells.
AB  - To investigate the molecular mechanisms mediating hematopoietic cell
      differentiation and mitogenesis by activation of the platelet-derived growth
      factor beta receptor (PDGF-betaR), the wild type PDGF-betaR (PDGF-betaRWT) and
      tyrosine to phenylalanine mutants of the PDGF-betaR, including F751, F966, F970,
      F1009, F1021 and F1009/F1021 were overexpressed in FDC-P2 myeloid progenitor
      cells by retroviral-mediated gene transfer. Stimulation of PDGF-betaRWT and F966,
      F970 and F1009 infectants with PDGF-BB led to the increased expression of
      monocytic differentiation markers. In contrast, activation of PDGF-betaR in the
      parental line or the F1021 or F1009/F1021 mutant infectants failed to induce
      monocytic differentiation. PDGF-BB stimulation of PDGF-betaRWT, F751, F966, F970
      and F1009 infectants led to pronounced DNA synthesis, whereas F1021 and
      F1009/F1021 infectants did not reveal any increase in mitogenesis when compared
      to that of the FDC-P2 line. While PDGF stimulation of FDC-P2 cells overexpressing
      PDGF-betaRWT led to a pronounced increase in inositol phosphate formation due to
      phospholipase C-gamma (PLC-gamma) activation, PDGF-BB induced phosphoinositol
      hydrolysis was completely abolished in the F1021 and F1009/F1021 infectants. GF
      109203X, a specific inhibitor of protein kinase C (PKC) activation, fully blocked
      PDGF-betaR-mediated monocytic differentiation and mitogenesis. Taken together,
      these results suggest that stimulation of the PDGF-betaR signaling pathway can
      mediate monocytic differentiation when PDGF-betaR is expressed at sufficient
      levels and that activation of PLC-gamma and PKC plays a pivotal role in PDGF
      betaR-mediated differentiation and mitogenesis in FDC-P2 cell system.

PMID- 9247313
TI  - The G12 coupled thrombin receptor stimulates mitogenesis through the Shc SH2
      domain.
AB  - Our previous studies in 1321N1 astrocytoma cells demonstrate that thrombin
      stimulates Ras-dependent mitogenesis through the pertussis toxin insensitive G
      protein G12. While the direct effectors of G12 are unknown, G12 can transform
      fibroblasts, utilize Ras and Rac dependent signaling pathways and stimulate GTP
      loading of Ras. Here we have examined the role of the Shc adaptor protein in
      mitogenic signaling by the thrombin receptor in 1321N1 cells. As has been
      reported in other systems, thrombin stimulation results in tyrosine
      phosphorylation of Shc in 1321N1 cells. We also show that transient expression of
      G alpha12 results in tyrosine phosphorylation of Shc, thereby identifying Shc as
      the most proximal G12 effector to date. In addition, we demonstrate by
      microinjection that thrombin stimulated mitogenesis requires Shc and occurs
      specifically through the Shc SH2 domain. Expression of the SH2 domain of Shc also
      inhibits G alpha12 mediated induction of an AP-1 dependent reporter gene
      demonstrating that G12 utilizes Shc to propagate downstream signals. Our data
      indicate that Shc is essential for stimulation of Ras dependent mitogenesis and
      gene expression by the G12 coupled thrombin receptor.

PMID- 9247314
TI  - Enhanced apoptosis in the thymus of transgenic mice expressing constitutively
      activated forms of human Rac2GTPase.
AB  - Rac proteins constitute a subgroup of the Rho family of small GTPases and include
      Rac1, which is expressed ubiquitously, and Rac2, a highly homologous protein only
      expressed in myelo-monocytic and lymphoid cell lineages. In fibroblasts, Rac1
      plays a crucial role in control of actin cytoskeleton organisation, cell growth
      and Ras-induced transformation. In phagocytes, Rac1 and Rac2 regulate a specific
      enzymatic complex, NADPH oxidase. These multiple functions have been ascribed to
      Rac proteins only on the basis of cell culture and in vitro biochemical studies.
      To examine the role of Rac2 in vivo in a T cell lineage, we have expressed either
      wild-type or constitutively-activated forms of human Rac2 (Rac2V12 and Rac2L61)
      in transgenic mice under control of the thymus specific lck proximal promoter. We
      report here a striking atrophy of the thymus in mice expressing even low levels
      of either of the activated mutants of Rac2, while expression of Rac2wt has no
      effect. This phenotype is correlated with a marked decrease in the number of
      double positive (CD4+ CD8+) and single positive (CD4+ CD8- and CD8+ CD4-)
      thymocytes. Cellular and molecular analyses demonstrate that this defect is due
      to an increase in apoptosis among thymocytes. As Rac2 is normally expressed in
      thymocytes and activated T cells, we propose that Rac2 dependent pathways could
      play an important role in control of growth and death of T cells.

PMID- 9247315
TI  - Oncogenes belonging to the CSF-1 transduction pathway direct p53 tumor suppressor
      effects to monocytic differentiation in 32D cells.
AB  - Expression of exogenous wt-p53 in different tumor cell lines can induce growth
      arrest, apoptosis, or differentiation. Several experimental works have
      highlighted the relevance of cellular context in the determination of p53
      mediated final outcomes. We recently observed that these diverse wt-p53 effects
      can also be induced by overexpressing wt-p53 in a single cell type-the 32D
      myeloid progenitors-transformed with different activated oncogenes. Here we show
      that 32D cells transformed with two different oncogenes, v-src or c-fms
      [S301,F969], both belonging to the CSF-1 transduction pathway, respond to
      exogenous wt-p53 expression with the same final outcome-monocytic
      differentiation. This result is particularly significant since 32D cells do not
      spontaneously express the CSF-1 receptor, whereas they undergo granulocytic
      differentiation upon G-CSF stimulation. These data strongly support the idea that
      wt-p53 suppressing effects result from interactions between p53 activity and the
      signaling pathways activated in different transformed cells.

PMID- 9247316
TI  - Characterization of murine Flt4 ligand/VEGF-C.
AB  - Flt4 is a receptor protein tyrosine kinase that is expressed in the adult
      lymphatic endothelium and high endothelial venules. We have used a BIAcore assay
      to identify rodent and human cell conditioned media containing the ligand of Flt4
      (Flt4-L). Receptor-based affinity chromatography was used to purify this growth
      factor, followed by amino acid sequencing and molecular cloning of the murine
      cDNA, the orthologue of human vascular endothelial growth factor-C and vascular
      endothelial growth factor related protein. The murine flt4-L gene was localized
      to chromosome 8 and demonstrated to be widely expressed. Flt4-L was found to have
      a hydrophobic signal sequence and a pro-peptide-like sequence that is removed to
      generate the mature N-terminus. In addition, the C-terminal region of Flt4-L has
      four repeats of a cysteine-rich motif that is presumably also proteolytically
      processed to generate the 21000 Mr polypeptide subunit of the Flt4-L homodimer.
      Recombinant Flt4-L activated Flt4 as judged by induction of tyrosyl
      phosphorylation, and induced mitogenesis in vitro of lymphatic endothelial cells.

PMID- 9247317
TI  - Endocrine functions in young men exposed for one night to a 50-Hz magnetic field.
      A circadian study of pituitary, thyroid and adrenocortical hormones.
AB  - In recent years, some epidemiologic studies have suggested that extremely low
      frequency magnetic and electric fields might affect human health, and, in
      particular, that the incidence of certain types of cancer, depression, and
      miscarriage might increase among individuals living or working in environments
      exposed to such fields. Work in our laboratory studies whether and how changes in
      the electromagnetic environment might affect human health. The study presented
      here was designed to look for possible effects of acute exposure to 50-Hz
      linearly polarized magnetic fields (10 microT) on the hormones of the
      hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. Thirty
      two young men (20-30 years old) were divided into two groups (sham-exposed or
      control group, and exposed group) of 16 subjects each. All subjects participated
      in two 24-hour experiments to evaluate the effects of both continuous and
      intermittent (one hour "off" and one hour "on" with the field switched "on" and
      "off" every 15 seconds) exposure to linearly polarized magnetic fields. The
      subjects were exposed to the magnetic field (generated by three Helmholtz coils
      per bed) from 2300 to 0800 while recumbent. Blood samples were collected during
      each session at 3 hour intervals from 1100 to 2000 and hourly from 2200 to 0800.
      Total urine was collected every 3 hours from 0800 to 2300 and then again at 0800.
      No significant differences were observed between sham-exposed and exposed men for
      any of the parameters measured: thyroid-stimulating hormone, follicle-stimulating
      hormone, luteinizing hormone, triiodothyronine, thyroxine, free triiodothyronine,
      free thyroxine, thyroxine-binding globulin, cortisol, 17-hydroxycorticosteroids
      (17-OH-CS) and TBK. These results suggest that acute exposure to either
      continuous or intermittent 50-Hz linearly polarized magnetic fields of 10 microT
      does not affect, at least under our experimental conditions, these endocrine
      functions or their circadian rhythmicity in healthy young men.

PMID- 9247318
TI  - Purification and cellular localization of beta2-microglobulin in the testis.
AB  - Using multiple high performance liquid chromatography (HPLC) steps, a protein of
      12 kDa was purified to apparent homogeneity from rat Sertoli cell-enriched
      culture medium (SCCM). Partial N-terminal amino acid sequence analysis revealed a
      sequence of NH2-IQKTPQIQVYS which is identical to beta2-microglobulin (beta2MG)
      previously identified in the brain. Studies by sequential reverse transcription
      and polymerase chain reaction (RT-PCR) indicated that beta2MG mRNA was expressed
      in Sertoli but not in germ cells suggesting that Sertoli cells are the source of
      this protein in the seminiferous epithelium behind the blood-testis barrier. The
      steady-state beta2MG mRNA level in Sertoli cells cultured in vitro was not
      affected by either follicle stimulating hormone (FSH), testosterone, estradiol,
      dexamethasone or several cytokines such as interleukin-1beta (IL-1beta),
      interleukin 6 (IL-6), and transforming growth factor beta (TGF-beta), with the
      exception of interferon-gamma (INFgamma) which induced a dose-dependent
      stimulation of beta2MG mRNA. The possible physiological significance of this
      protein in the male reproductive tract is discussed.

PMID- 9247319
TI  - Depletion of nigrostriatal and forebrain tyrosine hydroxylase by S
      adenosylmethionine: a model that may explain the occurrence of depression in
      Parkinson's disease.
AB  - The loss of nigrostriatal tyrosine hydroxylase (TH), dopamine and dopaminergic
      neurons are the major pathology of Parkinson's disease (PD). These
      catecholaminergic changes are responsible for the symptoms of tremor, hypokinesia
      and rigidity. Depression is also a major symptom in PD, but the cause is unknown.
      The impairments of catecholaminergic fibers in the frontal lobe may be involved,
      because the frontal lobe of the cerebrum is involved in the regulation of mood,
      and decreased catecholaminergic activity in the frontal lobe is related to
      behavioral depression. The changes that damage the nigrostriatal dopamine system
      and induce motor impairments may also damage the forebrain catecholamine fibers
      and induce depression. It means that manipulations that damage the nigrostriatum
      (NS) and induce parkinsonism may also deplete TH in the frontal cortex. Such an
      effect would suggests a basis for the depression seen in PD. The injection of S
      adenosyl-L-methionine (SAM), the biological methyl donor, into the brain of rats
      damaged the NS, depleted TH and caused tremor and hypokinesia. SAM may interfere
      also with the forebrain TH, which may help to explain the occurrence of
      depression in PD. Experiments were designed to test such a hypothesis. The
      results showed that SAM caused a loss of immunoreactive nerve fibers and it
      decreased the intensity of TH-immunoreactivity (IR) in the frontal cortex. These
      changes were accompanied with the loss of cells and the depletion of TH-IR from
      nerve fibers in the SN and the caudate nucleus. Other studies showed that SAM
      depletes DA and since SAM induces PD-like changes the results may be relevant to
      the co-occurrence of PD symptoms and depression. A single biological manipulation
      may impair the nigrostriatal dopaminergic neurons as well as the frontal cortex
      catecholaminergic fibers.

PMID- 9247320
TI  - Effect of angiotensin II on a spinal nociceptive reflex in the rat: receptor and
      mechanism of action.
AB  - The effect on thermonociceptive threshold of intrathecally (i.t.) administered
      angiotensin II (Ang II) was assessed in the rat tail-flick test. Rats were
      pretreated, 15 min earlier, with i.t. naloxone (opiate antagonist), losartan (Ang
      II selective antagonist at AT1 receptor) or [Sar1, Leu8] Ang II (non selective
      Ang II receptor antagonist) to define the mechanism of action and the nature of
      the receptor subtype. Ang II (0.65-6.5 nmol) induced antinociceptive effects that
      peaked at 1 min post-injection and returned to baseline after 5-10 min. Naloxone
      (10 microg) completely inhibited the response to 6.5 nmol Ang II. Losartan (65
      pmol) and [Sar1, Leu8] Ang II (6.5 nmol) blocked the antinociception induced by
      Ang II but were inactive against [MePhe7]neurokinin B. Furthermore, losartan
      failed to affect the hyperalgesic responses induced by substance P (6.5 nmol) or
      [beta-Ala8]neurokinin A (6.5 nmol). This study provides the first functional
      evidence that Ang II inhibits the transmission of thermal nociceptive information
      through an endogenous opioid mechanism and the activation of an AT1 receptor in
      the rat spinal cord.

PMID- 9247321
TI  - Impairment of muscarinic stimulation of adenylyl cyclase by heparin in rat
      olfactory bulb.
AB  - In rat olfactory bulb membranes, the stimulation of adenylyl cyclase by the
      cholinergic agonist carbachol (CCh) was markedly inhibited by heparin at
      concentrations (0.3-10 microM) that had smaller or no effects on the enzyme
      stimulations elicited by vasoactive intestinal peptide, pituitary adenylate
      cyclase activating polypeptide (PACAP), 1-isoproterenol and corticotropin
      releasing hormone. Heparin did not significantly affect the binding of [3H]N
      methylscopolamine ([3H]NMS) to muscarinic receptors, but decreased the potency of
      CCh in displacing the bound radioligand in a manner similar to that of the GTP
      analogue guanosine-5'-O-(3'-thio)triphosphate (GTPgammaS). Heparin inhibited the
      binding of [35S]GTPgammaS to membrane G proteins stimulated by CCh more potently
      than that elicited by PACAP. Moreover, at the same concentrations, heparin
      inhibited the muscarinic inhibition of adenylyl cyclase in rat striatal
      membranes. These data indicate that heparin impairs the muscarinic stimulation of
      olfactory bulb adenylyl cyclase likely by interfering with the receptor-induced
      activation of G proteins. The higher sensitivity to heparin of this response as
      compared to those displayed by Gs-mediated enzyme stimulations provides further
      evidence that Gi/Go, rather than Gs, mediate the muscarinic stimulation of
      adenylyl cyclase in rat olfactory bulb.

PMID- 9247322
TI  - Effect of acidotic challenges on local depolarizations evoked by N-methyl-D
      aspartate in the rat striatum.
AB  - We have examined how various challenges to brain acid-base homeostasis, resulting
      in extracellular acidosis, alter N-methyl-D-aspartate (NMDA)-evoked
      depolarizations in vivo. Repeated stimuli were produced by perfusion of 200
      microM NMDA for 2 min through a microdialysis probe implanted into the striatum
      of halothane anesthetized rats. Hypercapnia reduced NMDA-evoked responses in a
      concentration-dependent manner, with 7.5 and 15 % CO2 in the breathing mixture
      reducing the depolarization amplitude to 74 % and 64 % of that of the initial
      stimuli, respectively. Application of 50 mM NH4+ progressively reduced dialysate
      pH, and a further acidification was observed when NH4+ was discontinued.
      Perfusion of NMDA after NH4+ application evoked smaller depolarizations (56 % of
      the corresponding control, 5 min after NH4+ removal), and this effect persisted
      for over 1 h. Perfusion of acidic ACSF did not alter the amplitude of NMDA-evoked
      depolarization, despite changes in dialysate pH confirming that
      exchange/buffering of acid equivalents took place between the perfusion medium
      and the surrounding tissue. This negative result probably reflected the
      remarkable capacity of the brain to buffer H+. Together, these results
      demonstrate that extracellular acidosis, such as that associated with excessive
      neuronal activation or ischemia, inhibits NMDA-evoked responses in vivo.

PMID- 9247323
TI  - New spin labeled analogues of podophyllotoxin as potential antitumor agents.
AB  - Four new nitroxyl labeled derivatives of podophyllotoxin, 4-(2, 2, 6, 6
      tetramethyl-1-oxyl-4-piperidyl)oxy-epipodophyllotoxin (4), 4-(2, 2, 6, 6
      tetramethyl-1-oxyl-4-piperidyl)oxy-4'-demethylepipodophyllotoxin (5), 4-(2, 2, 5,
      5-tetramethyl-1-oxyl-3-pyrrolinyl)formyloxy-epipodophyllotox in (6) and 4-(2, 2,
      5, 5-tetramethyl-1-oxyl-3-pyrrolinyl)formyloxy-4'-demethylep ipodophyllotoxin
      (7), have been synthesized and evaluated for their antitumor activity in vitro.
      Compounds 5 and 7 showed superior activity to clinically used etoposide (VP-16,2)
      in their inhibition of leukemia P388, lung cancer A549 and stomach carcinoma SGC
      7901 cells. 4'-Demethyl-epipodophyllotoxins 5 and 7 was found to be more active
      than eipodophyllotoxins 4 and 6 lacking a free phenolic hydroxyl group at C-4'.

PMID- 9247324
TI  - mRNAs encoding CCKB but not CCKA receptors are expressed in human T lymphocytes
      and Jurkat lymphoblastoid cells.
AB  - We previously reported the existence of pharmacologically related gastrin/CCKB
      type receptors (CCKB-R) in a variant of Jurkat T lymphoblastoid cells (JK(CD3-
      CD4+)). We studied here the expression of mRNAs encoding CCKA and CCKB receptors
      in various human white cells by means of Reverse Transcription-Polymerase Chain
      Reaction (RT-PCR). Using CCKB-R specific primers, we detected a significant
      expression of CCKB-R mRNA in JK(CD3- CD4+) cells. These transcripts were also
      expressed, at a lower level, in two other Jurkat clones (JK(CD3+ CD4-) and
      JK(CD3+ CD4+)), in peripheral blood lymphocytes (PBL) and in purified CD4+ and
      CD8+ lymphocytes. Activation of Jurkat cells and PBL by T cells mitogenic lectins
      (jacalin, phytohemaglutinin) did not modify CCKB-R mRNA expression. In all these
      cells, using CCKA-R specific primers, we could not amplify any specific cDNA
      fragment corresponding to this receptor. Neither CCKB-R nor CCKA-R mRNAs could be
      detected in monocytic cells. Our data show for the first time a constitutive
      expression of CCKB-R transcripts in lymphoid cells. Moreover, the modulation of
      immunocyte functions by cholecystokinin-related peptides could occur through CCKB
      R rather than CCKA-R and affect lymphocytes rather than monocytes.

PMID- 9247326
TI  - The cortisol response to psychological challenge is preceded by a transient rise
      in endogenous inhibitor of monoamine oxidase.
AB  - The salivary cortisol response to an acute psychological stress challenge was
      investigated in normal male undergraduate students. A modified version of the
      Trier Social Stress Test (TSST) was used and saliva collected on 6 occasions
      before during and after the stress challenge. Control subjects were allowed to
      read quietly. As expected the cortisol response in experimental subjects was
      robust and peaked 12 minutes after the end of the stress. Endogenous monoamine
      oxidase A inhibitory activity (MAO-AI) was measured in the same saliva samples.
      MAO-AI also changed in response to the stress challenge, peaking in the saliva
      sample collected immediately after the stress challenge, 12 minutes prior to the
      cortisol peak sample. Furthermore the degree of increase in salivary MAO-AI was
      found to predict the degree of cortisol increase in the test subjects (r=0.76;
      n=14; p<0.001). These results are consistent with the hypothesis that elevated
      central monoamines, driven by inhibition of their main metabolic enzyme, can
      activate the hypothalamic-pituitary-adrenal (HPA) axis in the stress response.
      This finding lends further support to the notion that endogenous generation of
      MAO-AI is a normal homeostatic regulatory mechanism.

PMID- 9247325
TI  - Stimulatory action of endothelin-1 on rat Leydig cells: involvement of endothelin
      A subtype receptor and phospholipase A2-arachidonate metabolism system.
AB  - In a previous report we have observed that endothelin-1 (ET-1) is able to
      stimulate testosterone (T) production by rat Leydig cells revealing an
      interaction with human chorionic gonadotropin (hCG). The present study was
      designed to further characterize the stimulatory action of ET on testicular
      steroidogenesis, to evaluate which subtype of ET receptors is involved in this
      activity and to examine the role of phospholipase A2 (PLA2)-arachidonate
      metabolism system in ET-1 transduction mechanism. To this purpose we
      investigated: i) the interaction of ET-1 with another secretagogue of T, like
      luteinizing hormone releasing hormone (LHRH); ii) the interference of ET(A) and
      ET(B) receptor antagonists (BQ-123 and BQ-788, respectively) and of inhibitors of
      PLA2 (quinacrine) and arachidonate lipoxygenase pathway (nordihydroguaiaretic
      acid:NDGA) on ET-1-induced T and PGE2 secretion from purified rat Leydig cells.
      Data obtained indicate that ET-1 amplified T and PGE2 response to LHRH and this
      secretagogue in turn potentiated testicular steroidogenesis stimulated by
      endothelin. The ET(A) antagonist, BQ-123, inhibited in a dose-related fashion ET
      1-induced T production whereas ET(B) antagonist, BQ-788, failed to affect T
      response to the peptide. Furthermore, ET(A) antagonist inhibited the stimulatory
      effect of ET-1 on hCG- or LHRH-induced T secretion and it was able to exert a
      dose-dependent inhibition of ET-1-stimulated PGE2 output. Moreover, a PLA2
      inhibitor quinacrine inhibited the stimulatory action of ET-1 on T production and
      suppressed basal and ET-1-induced PGE2 release whilst a lipoxygenase blocker NDGA
      did not modify T response to the peptide. Taken together these findings i)
      indicate additivity of effects between ET-1 and LHRH in stimulating T and PGE2
      production; ii) confirm that ET(A) subtype receptors mediate the stimulatory
      action of ET-1 on rat Leydig cells; iii) strongly suggest that PLA2-arachidonate
      metabolism system is involved in endothelin transduction mechanism.

PMID- 9247327
TI  - Acute interaction between ethanol and serotonin metabolism in the rat.
AB  - The effect of acute ethanol on peripheral serotonin (5HT) metabolism was studied
      in Sprague-Dawley rats. Four hours after a single dose of ethanol (1.0 g/kg)
      administered into the stomach, a significant increase in the 5HT level in stomach
      tissue and a decrease in ileum was observed. The level of 5-hydroxyindole-3
      acetic acid (5HIAA) was increased in urine, while increased concentrations of 5
      hydroxytryptophol (5HTOL) occurred in jejunum, ileum, spleen and urine. After 7-9
      h when the blood ethanol concentration had returned to zero, 5HTOL levels were
      still higher than control values in jejunum, ileum and urine. At 4 h, an elevated
      ratio of 5HTOL to 5HIAA was observed in urine and ileum (by approximately 2
      fold), liver (approximately 3-fold), and spleen (approximately 5-fold), whereas
      the ratio was reduced in stomach. In urine and spleen, this metabolic shift
      persisted after 7-9 h. The 5HTOL level in bile was increased by approximately 3.5
      fold after 8 h. 5HIAA was not detectable in bile. The present results indicate
      that the rat has a much higher proportion of 5HTOL formation than man under
      normal conditions. The rat does not appear to be an ideal model for studying the
      interaction between ethanol and 5HT metabolism in man.

PMID- 9247328
TI  - The structure of the promoter region for rat inducible nitric oxide synthase
      gene.
AB  - The nucleotide sequences of the promoter region for rat inducible nitric oxide
      synthase (iNOS) were elucidated. The sequences were highly homologous with the
      mouse iNOS gene. The regulation of the iNOS gene may be distinguished between
      rodent and mammalian.

PMID- 9247329
TI  - Genetic separation of the neural and cuticular patterning functions of
      gooseberry.
AB  - In addition to their role in the specification of the epidermal pattern in each
      segment, several segment polarity genes, including gooseberry (gsb), specify cell
      fate in the Drosophila central nervous system (CNS). Analyses of the gsb CNS
      phenotype have been complicated by the fact that the previously available gsb
      mutants, all caused by cytologically visible deficiencies, have severe
      segmentation defects and also lack a number of additional genes. We have
      characterized two novel gsb mutants which, due to their hypomorphic nature, have
      CNS defects, but have only weak or no segmentation defects. These gsb alleles, as
      well as gsb rescue experiments, have allowed us to determine which aspects of the
      deficiency mutant phenotypes can be attributed to loss of gsb. gsb mutants lack U
      and CQ neurons, have duplicated RP2 neurons, and display posterior commissure
      defects. gsb neural defects, as well as the gsb cuticle defect, are
      differentially sensitive to the level of functional Gsb. We have used one of the
      novel gsb alleles in order to understand the genetic interactions between gsb,
      wingless (wg), and patched (ptc) during the patterning of the ventral
      neuroectoderm. In contrast to epidermal patterning, where Gsb is required to
      maintain wg transcription, we find that Gsb antagonizes the Wg signal that
      confers neuroblast (NB) 4-2 fate.

PMID- 9247330
TI  - First evidence of a calcium transient in flowering plants at fertilization.
AB  - We report here the first evidence of a transient elevation of free cytosolic Ca2+
      following fusion of sperm and egg cell in a flowering plant by the use of an in
      vitro fertilization system recently developed in maize. Imaging changes in
      cytosolic Ca2+ at fertilization was undertaken by egg cell loading with the
      fluorescent Ca2+ indicator dye fluo-3 under controlled physiological conditions.
      The gamete adhesion step did not induce any cytosolic Ca2+ variation in the egg
      cell, whereas the fusion step triggered a transient cytosolic Ca2+ rise in the
      fertilized egg cell, lasting several minutes. This rise occurred after the
      establishment of gamete cytoplasm continuity. Through these observations, we open
      the way to the identification of the early signals induced by fertilization in
      flowering plants that give rise to the calcium transient and to investigations of
      the role of Ca2+ during egg activation and early zygote development in plants, as
      has been reported for other better characterized animal and algae systems.

PMID- 9247331
TI  - The role of lin-22, a hairy/enhancer of split homolog, in patterning the
      peripheral nervous system of C. elegans.
AB  - In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are
      located in a row along the anterior-posterior (A/P) body axis. Anterior seam
      cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and
      generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more
      complicated sequence of cell divisions that include additional rounds of stem
      cell proliferation and the production of neural as well as epidermal cells. In
      the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal
      epidermal lineages rather than V5-like lineages. lin-22 activity is also required
      to prevent additional neurons from being produced by one branch of the V5
      lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene
      hairy, and that lin-22 activity represses neural development within the V5
      lineage by blocking expression of the posterior-specific Hox gene mab-5 in
      specific cells. In addition, in order to prevent anterior V cells from generating
      V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or
      indirectly) at least five downstream regulatory gene activities. In anterior body
      regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits
      the activity of the achaete-scute homolog lin-32 and an unidentified gene that we
      postulate regulates stem cell division. Each of these three genes is required for
      the expression of a different piece of the ectopic V5-like lineages generated in
      lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39
      and egl-5, from acquiring new activities within their normal domains of function
      along the A/P body axis. Some, but not all, of the patterning activities of lin
      22 in C. elegans resemble those of hairy in Drosophila.

PMID- 9247332
TI  - An actin-mediated two-step mechanism is required for ventral enclosure of the C.
      elegans hypodermis.
AB  - The epiboly of the Caenorhabditis elegans hypodermis involves the bilateral
      spreading of a thin epithelial sheet from the dorsal side around the embryo to
      meet at the ventral midline in a process known as ventral enclosure. We present
      evidence that ventral enclosure occurs in two major steps. The initial migration
      of the hypodermis is led by a quartet of cells, which exhibit protrusive activity
      at their medial tips and are required to pull the hypodermis around the equator
      of the embryo. These cells display actin-rich filopodia and treatment with
      cytochalasin D immediately halts ventral enclosure, as does laser inactivation of
      all four cells. Once the quartet of cells has migrated around the equator of the
      embryo and approaches the ventral midline, the remainder of the leading edge
      becomes visible on the ventral surface and exhibits a localization of actin
      microfilaments along the free edges of the cells, forming an actin ring.
      Cytochalasin D and laser inactivation block ventral enclosure at this later stage
      as well and, based upon phalloidin staining, we propose that the second half of
      enclosure is dependent upon a purse string mechanism, in which the actin ring
      contracts and pulls together the edges of the hypodermal sheet at the ventral
      midline. The ventral cells then form junctions with their contralateral neighbors
      to complete ventral enclosure.

PMID- 9247333
TI  - Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a
      subpopulation of embryonic motoneurons.
AB  - Muscle-derived factors are known to be important for the survival of developing
      spinal motoneurons, but the molecules involved have not been characterized.
      Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in
      muscle development and motoneuron axon outgrowth. We show that HGF/SF has potent
      neurotrophic activity (EC50=2 pM) for a subpopulation (40%) of purified embryonic
      rat motoneurons. Moreover, HGF/SF is an essential component of muscle-derived
      support for motoneurons, since blocking antibodies to HGF/SF specifically
      inhibited 65% of the trophic activity of media conditioned by C2/C7 skeletal
      myotubes, but did not inhibit the trophic activity secreted by Schwann cell
      lines. High levels of expression of the HGF/SF receptor c-Met in the spinal cord
      are restricted to subsets of motoneurons, mainly in limb-innervating segments.
      Consistent with this distribution, cultured motoneurons from limb-innervating
      brachial and lumbar segments showed a more potent response to HGF/SF than did
      thoracic motoneurons. By the end of the period of motoneuron cell death, levels
      of c-Met mRNA in motoneurons were markedly reduced, suggesting that the effects
      of HGF/SF may be limited to the period of motoneuron cell death. HGF/SF may play
      an important role during motoneuron development as a muscle-derived survival
      factor for a subpopulation of limb-innervating motoneurons.

PMID- 9247334
TI  - Control of cell fates and segmentation in the Drosophila mesoderm.
AB  - The primordia for heart, fat body, and visceral and somatic muscles arise in
      specific areas of each segment in the Drosophila mesoderm. We show that the
      primordium of the somatic muscles, which expresses high levels of twist, a
      crucial factor of somatic muscle determination, is lost in sloppy-paired mutants.
      Simultaneously, the primordium of the visceral muscles is expanded. The visceral
      muscle and fat body primordia require even-skipped for their development and the
      mesoderm is thought to be unsegmented in even-skipped mutants. However, we find
      that even-skipped mutants retain the segmental modulation of the expression of
      twist. Both the domain of even-skipped function and the level of twist expression
      are regulated by sloppy-paired. sloppy-paired thus controls segmental allocation
      of mesodermal cells to different fates.

PMID- 9247335
TI  - Specification of the anterior hindbrain and establishment of a normal
      mid/hindbrain organizer is dependent on Gbx2 gene function.
AB  - Analysis of mouse embryos homozygous for a loss-of-function allele of Gbx2
      demonstrates that this homeobox gene is required for normal development of the
      mid/hindbrain region. Gbx2 function appears to be necessary at the neural plate
      stage for the correct specification and normal proliferation or survival of
      anterior hindbrain precursors. It is also required to maintain normal patterns of
      expression at the mid/hindbrain boundary of Fgf8 and Wnt1, genes that encode
      signaling molecules thought to be key components of the mid/hindbrain (isthmic)
      organizer. In the absence of Gbx2 function, isthmic nuclei, the cerebellum, motor
      nerve V, and other derivatives of rhombomeres 1-3 fail to form. Additionally, the
      posterior midbrain in the mutant embryos appears to be extended caudally and
      displays abnormalities in anterior/posterior patterning. The failure of anterior
      hindbrain development is presumably due to the loss of Gbx2 function in the
      precursors of the anterior hindbrain. However, since Gbx2 expression is not
      detected in the midbrain it seems likely that the defects in midbrain
      anterior/posterior patterning result from an abnormal isthmic signaling center.
      These data provide genetic evidence for a link between patterning of the anterior
      hindbrain and the establishment of the mid/hindbrain organizer, and identify Gbx2
      as a gene required for these processes to occur normally.

PMID- 9247337
TI  - Musculoskeletal patterning in the pharyngeal segments of the zebrafish embryo.
AB  - The head skeleton and muscles of the zebrafish develop in a stereotyped pattern
      in the embryo, including seven pharyngeal arches and a basicranium underlying the
      brain and sense organs. To investigate how individual cartilages and muscles are
      specified and organized within each head segment, we have examined their early
      differentiation using Alcian labeling of cartilage and expression of several
      molecular markers of muscle cells. Zebrafish larvae begin feeding by four days
      after fertilization, but cartilage and muscle precursors develop in the
      pharyngeal arches up to 2 days earlier. These chondroblasts and myoblasts lie
      close together within each segment and differentiate in synchrony, perhaps
      reflecting the interdependent nature of their patterning. Initially, cells within
      a segment condense and gradually become subdivided into individual dorsal and
      ventral structures of the differentiated arch. Cartilages or muscles in one
      segment show similar patterns of condensation and differentiation as their
      homologues in another, but vary in size and shape in the most anterior
      (mandibular and hyoid) and posterior (tooth-bearing) arches, possibly as a
      consequence of changes in the timing of their development. Our results reveal a
      segmental scaffold of early cartilage and muscle precursors and suggest that
      interactions between them coordinate their patterning in the embryo. These data
      provide a descriptive basis for genetic analyses of craniofacial patterning.

PMID- 9247336
TI  - Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive
      erythrocyte development.
AB  - We investigated the function of Lhx2, a LIM homeobox gene expressed in developing
      B-cells, forebrain and neural retina, by analyzing embryos deficient in
      functional Lhx2 protein. Lhx2 mutant embryos are anophthalmic, have malformations
      of the cerebral cortex, and die in utero due to severe anemia. In Lhx2-/- embryos
      specification of the optic vesicle occurs; however, development of the eye
      arrests prior to formation of an optic cup. Deficient cellular proliferation in
      the forebrain results in hypoplasia of the neocortex and aplasia of the
      hippocampal anlagen. In addition to the central nervous system malformations, a
      cell non-autonomous defect of definitive erythropoiesis causes severe anemia in
      Lhx2-/- embryos. Thus Lhx2 is necessary for normal development of the eye,
      cerebral cortex, and efficient definitive erythropoiesis.

PMID- 9247338
TI  - Pax-6 is involved in the specification of hindbrain motor neuron subtype.
AB  - Pax-6 is a member of the vertebrate Pax gene family, which is structurally
      related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed
      in several discrete domains of the developing CNS and has been implicated in
      neural development, although its precise role remains elusive. We found a novel
      Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye.
      Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding
      the region downstream of the paired box of the Pax-6 gene, resulting in
      generation of truncated protein due to the frame shift. To explore the roles of
      Pax-6 in neural development, we searched for abnormalities in the nervous system
      in rSey2 homozygous embryos. rSey2/rSey2 exhibited abnormal development of motor
      neurons in the hindbrain. The Islet-1-positive motor neurons were generated just
      ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos.
      However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were
      missing in homozygous embryos. By retrograde and anterograde labeling, we found
      no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain,
      though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing)
      were observed within the neural tube. To discover whether the identity of these
      motor neuron subtypes was changed in the mutant, we examined expression of LIM
      homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the
      hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type
      neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2
      expression was specifically missing, which resulted in the loss of the cells
      harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3).
      Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in
      the ventrolateral domain of the neural tube, was also specifically missing in the
      mutant hindbrain, while it remained intact in the dorsal non-overlapping domain.
      These results strongly suggest that Pax-6 is involved in the specification of
      subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2
      and Wnt-7b expression.

PMID- 9247339
TI  - Serrate-mediated activation of Notch is specifically blocked by the product of
      the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc.
AB  - In the developing imaginal wing disc of Drosophila, cells at the dorsoventral
      boundary require localized Notch activity for specification of the wing margin.
      The Notch ligands Serrate and Delta are required on opposite sides of the
      presumptive wing margin and, even though activated forms of Notch generate
      responses on both sides of the dorsoventral boundary, each ligand generates a
      compartment-specific response. In this report we demonstrate that Serrate, which
      is expressed in the dorsal compartment, does not signal in the dorsal regions due
      to the action of the fringe gene product. Using ectopic expression, we show that
      regulation of Serrate by fringe occurs at the level of protein and not Serrate
      transcription. Furthermore, replacement of the N-terminal region of Serrate with
      the corresponding region of Delta abolishes the ability of fringe to regulate
      Serrate without altering Serrate-specific signaling.

PMID- 9247340
TI  - The prechordal region lacks neural inducing ability, but can confer anterior
      character to more posterior neuroepithelium.
AB  - The avian equivalent of Spemann's organizer, Hensen's node, begins to lose its
      ability to induce a nervous system from area opaca epiblast cells at stage 4+,
      immediately after the full primitive streak stage. From this stage, the node is
      no longer able to induce regions of the nervous system anterior to the hindbrain.
      Stage 4+ is marked by the emergence from the node of a group of cells, the
      prechordal mesendoderm. Here we have investigated whether the prechordal region
      possesses the lost functions of the organizer, using quail-chick chimaeras to
      distinguish graft- and host-derived cells, together with several region-specific
      molecular markers. We find that the prechordal region does not have neural
      inducing ability, as it is unable to divert extraembryonic epiblast cells to a
      neural fate. However, it can confer more anterior character to prospective
      hindbrain cells of the host, making them acquire expression of the forebrain
      markers tailless and Otx-2. It can also rescue the expression of Krox-20 and Otx
      2 from nervous system induced by an older (stage 5) node in extraembryonic
      epiblast. We show that these properties reflect a true change of fate of cells
      rather than recruitment from other regions. The competence of neuroectoderm to
      respond to anteriorizing signals declines by stages 7-9, but both posteriorizing
      signals and the ability of neuroectoderm to respond to them persist after this
      stage.

PMID- 9247341
TI  - Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes
      a truncation of the anterior neuroectoderm.
AB  - Transgenic embryos expressing Cwnt8C under the control of the human beta-actin
      promoter exhibit duplicated axes or a severely dorsalised phenotype. Although the
      transgene was introduced into fertilised eggs all duplications occurred within a
      single amnion and, therefore, arose from the production of more than one
      primitive streak at the time of gastrulation. Morphological examination and the
      expression of diagnostic markers in transgenic embryos suggested that ectopic
      Cwnt8C expression produced only incomplete axis duplication: axes were always
      fused anteriorly, there was a reduction in tissue rostral to the anterior limit
      of the notochord, and no duplicated expression domain of the forebrain marker
      Hesx1 was observed. Anterior truncations were evident in dorsalised transgenic
      embryos containing a single axis. These results are discussed in the light of the
      effects of ectopic Xwnt8 in Xenopus embryos, where its early expression leads to
      complete axis duplication but expression after the mid-blastula transition causes
      anterior truncation. It is proposed that while ectopic Cwnt8C in the mouse embryo
      can duplicate the primitive streak and node this only produces incomplete axis
      duplication because specification of the anterior aspect of the axis, as opposed
      to maintenance of anterior character, is established by interaction with anterior
      primitive endoderm rather than primitive streak derivatives.

PMID- 9247342
TI  - HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes.
AB  - Cyclin B-dependent CDC2 kinase activity has a key role in triggering the G2/M
      phase transition during the mitotic and meiotic cell cycles. The Hsp70-2 gene is
      expressed only in spermatogenic cells at a significant level. In Hsp70-2 gene
      knock-out (Hsp70-2(-/-)) mice, primary spermatocytes fail to complete meiosis I,
      suggesting a link between HSP70-2 heat-shock protein and CDC2 kinase activity
      during this phase of spermatogenesis. Members of the HSP70 protein family are
      molecular chaperones that mediate protein de novo folding, translocation and
      multimer assembly. This study used immunoprecipitation-coupled western blot and
      in vitro reconstitution experiments to show that HSP70-2 interacts with CDC2 in
      the mouse testis, appears to be a molecular chaperone for CDC2, and is required
      for CDC2/cyclin B1 complex formation. Previous studies reported that most CDC2
      kinase activity in the mouse testis is present in pachytene spermatocytes.
      Although CDC2 kinase activity for histone H1 was present in the testis of wild
      type mice, it was nearly absent from the testis of Hsp70-2(-/-) mice, probably
      due to defective CDC2/cyclin B1 complex formation. Furthermore, addition of HSP70
      2 to freshly prepared extracts of testis from Hsp70-2(-/-) mice not only restored
      CDC2/cyclin B1 complex formation but also reconstituted CDC2 kinase activity in
      vitro. It appears that one cause of failure to complete meiosis I during
      spermatogenesis in Hsp70-2(-/-) mice is disruption of CDC2/cyclin B1 assembly in
      pachytene spermatocytes, thereby preventing development of the CDC2 kinase
      activity required to trigger G2/M-phase transition. These studies provide novel
      in vivo evidence for a link between an HSP70 molecular chaperone and CDC2 kinase
      activity essential for the meiotic cell cycle in spermatogenesis.

PMID- 9247343
TI  - Nanos and pumilio establish embryonic polarity in Drosophila by promoting
      posterior deadenylation of hunchback mRNA.
AB  - Nanos protein promotes abdominal structures in Drosophila embryos by repressing
      the translation of maternal hunchback mRNA in the posterior. To study the
      mechanism of nanos-mediated translational repression, we first examined the
      mechanism by which maternal hunchback mRNA is translationally activated. In the
      absence of nanos activity, the poly(A) tail of hunchback mRNA is elongated
      concomitant with its translation, suggesting that cytoplasmic polyadenylation
      directs activation. However, in the presence of nanos the length of the hunchback
      mRNA poly(A) tail is reduced. To determine if nanos activity represses
      translation by altering the polyadenylation state of hunchback mRNA, we injected
      various in vitro transcribed RNAs into Drosophila embryos and determined changes
      in polyadenylation. Nanos activity reduced the polyadenylation status of injected
      hunchback RNAs by accelerating their deadenylation. Pumilio activity, which is
      necessary to repress the translation of hunchback, is also needed to alter
      polyadenylation. An examination of translation indicates a strong correlation
      between poly(A) shortening and suppression of translation. These data indicate
      that nanos and pumilio determine posterior morphology by promoting the
      deadenylation of maternal hunchback mRNA, thereby repressing its translation.

PMID- 9247344
TI  - Biospecific interactions of vitamin K-dependent factors with phospholipid-like
      polystyrene derivatives. Part II: factor IX.
AB  - We previously demonstrated that phosphorylated polystyrene derivatives exhibit
      phospholipid-like behaviour and therefore are able to interact with factor II,
      one of the vitamin K-dependent coagulation factors. Under the same conditions as
      for factor II, we examined the interactions of factor IX with phosphorylated
      resins of various compositions in phosphate groups: these studies were carried
      out with or without albumin precoating of the polymers and either in the presence
      or absence of calcium ions. Adsorption experiments show that, in the absence of
      calcium ions, only one class of adsorption sites of factor IX can be evidenced
      with the interactions taking place through the formation of binary complexes,
      whereas in the presence of calcium ions, the affinity of factor IX for
      phosphorylated resins becomes very high and two types of adsorption sites have
      been evidenced with biospecific ternary complexes being formed. The domains of
      predominance of these complexes were determined. Moreover, the only functional
      groups borne by the phosphorylated polystyrene resins involved in factor IX
      polymer interactions are phosphodiester groups. Comparison between factor II and
      factor IX adsorption onto the same polymers leads to the conclusion that the
      observed differences probably reflect the differences in the Gla domains of the
      vitamin K-dependent factors. Finally, this study demonstrates that phosphorylated
      polystyrene derivatives can be used as stationary phases for purification of
      factor IX by highly specific liquid biochromatography.

PMID- 9247345
TI  - Upscaling the production of microencapsulated pancreatic islets.
AB  - Presently used single-needle air-driven droplet generators are incapable of
      producing sufficient numbers of islet-containing droplets in a sufficiently short
      time-period to allow for successfully grafting alginate-poly-L-lysine
      encapsulated islets in large animals or humans. We have designed an air-driven
      multineedle droplet generator, which increases the production rate by
      simultaneously producing multiple droplets. Although we have tested a four-needle
      device, the construction is such that the number of needles, and thereby the
      production rate, can be readily extended. The production rate can be further
      extended by increasing the number of islets per millilitre alginate in the
      reservoir. When tested with 500 and 800 microm capsules, an increase in the
      number of islets per millilitre alginate was found to be associated with an
      increase in the number of inadequately encapsulated islets in a diameter
      dependent fashion. When small instead of large capsules are produced from a given
      volume of alginate, larger numbers of capsules are obtained, but also a larger
      portion of inadequate capsules. With 10,000 islets per millimetre alginate, these
      combined effects can be calculated to result in a two-fold increase in the
      production rate of adequate capsules when 500 microm instead of 800 microm
      capsules are produced. Hence, substantial upscaling of the production can be
      achieved by combining an increase in the number of needles with a decrease in the
      capsule diameter.

PMID- 9247346
TI  - Quantification of cell adhesion using a spinning disc device and application to
      surface-reactive materials.
AB  - Quantitative analysis of cell adhesion is essential in understanding
      physiological phenomena and developing biotechnological applications.
      Electrochemical measurements demonstrated that the transport patterns associated
      with a spinning disc device approximate the fluid flow and mass transport fields
      for a disc spinning in an infinite fluid. Therefore, this device applies a linear
      range of forces to attached cells under uniform and constant chemical conditions
      at the interface. The application of this apparatus for examining cell adhesion
      to surface-active materials was illustrated by investigating the attachment of
      osteoblast-like cells to fibronectin adsorbed onto bioactive and non-reactive
      glasses for different chemical environments. Cells were seeded on fibronectin
      coated substrates for 15 min and then subjected to detachment forces for 10 min.
      The number of adherent cells decreased non-linearly with applied force and the
      detachment profile was accurately described by a sigmoidal curve fit, as expected
      for a cell population with normally distributed adhesion properties.

PMID- 9247347
TI  - In vitro blood compatibility of functional group-grafted and heparin-immobilized
      polyurethanes prepared by plasma glow discharge.
AB  - Blood compatibilities of functional group-grafted and heparin-immobilized
      polyurethanes (PUs) were investigated using in vitro thrombus formation, plasma
      recalcification time (PRT), activated partial thromboplastin time (APTT),
      platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC)
      activation. In the experiment with plasma proteins, PRT was shortened on amine
      group-grafted PU (PU-NH2) but prolonged on heparin-immobilized polyurethane (PU
      Hep) when compared to PU control. APTT was significantly prolonged on PU-Hep,
      suggesting the binding of immobilized heparin to antithrombin III. The percentage
      of platelet adhesion was slightly increased by the introduction of functional
      groups such as carboxylic acid and primary amine on PU surfaces, but
      significantly decreased by the immobilization of heparin on the same substrate.
      The percentage of serotonin released from platelets adhered on surface-modified
      PUs was increased with increase of platelet adhesion. In the PBMC experiment,
      cells adhered less on heparin-immobilized PUs than on functional group-grafted
      PUs, and the production levels of tumour necrosis factor mRNAs from the cells
      stimulated by heparin-immobilized PU (PU-N-Hep) were smaller than those by the
      other substrates.

PMID- 9247348
TI  - Heparin in calcification prevention of porcine pericardial bioprostheses.
AB  - Calcific degeneration is the main cause of failure of glutaraldehyde-treated
      xenograft heart valve substitutes implanted in humans. Coupling of heparin
      through an intermediate surface-bound substrate containing amino groups showed
      complete prevention of calcification of glutaraldehyde-treated porcine
      pericardium implanted subdermally in weanling rats for 5 months (heparin bonded
      pericardium: calcium, 0.625 +/- 0.24 mg g(-1); glutaraldehyde-only-treated
      pericardium: calcium, 228.32 +/- 37.39 mg g(-1); P < 0.0001). Conceivably,
      inactivation of unpaired aldehyde moieties present in bioprostheses after
      exposure to glutaraldehyde by amino compounds followed by blocking the potential
      binding sites of the graft with a surface modifying agent like heparin would be
      the key steps in the prevention of calcification and degeneration of
      glutaraldehyde-treated biological tissue grafts.

PMID- 9247349
TI  - Cytotoxic, allergic and genotoxic activity of a nickel-titanium alloy.
AB  - The nearly equiatomic nickel-titanium (NiTi) alloy is known for its shape memory
      properties. These properties can be put to excellent use in various biomedical
      applications, such as wires for orthodontic tooth alignment and osteosynthesis
      staples. The aim of this study was to evaluate the short-term biological safety
      of the NiTi alloy. We carried out an end-point dilution minimal essential medium
      (MEM) extract cytotoxicity test, a guinea-pig sensitization test and two
      genotoxicity tests: the Salmonella reverse mutation test and the chromosomal
      aberration test. The NiTi alloy showed no cytotoxic, allergic or genotoxic
      activity, similar to the clinical reference control material AISI 316 LVM
      stainless steel. This promising biological behaviour was most likely due to a
      minimal release of ions and in that way a reflection of the good corrosion
      resistance of the NiTi alloy. Given these very good results, together with the
      good tissue compatibility as shown in several implantation studies in the
      literature, the NiTi alloy can be regarded as a biologically safe implant
      material with many promising clinical applications.

PMID- 9247350
TI  - Adsorption of chondroitin-4-sulphate and heparin onto titanium: effect of bovine
      serum albumin.
AB  - The adsorption of chondroitin-4-sulphate (C4S) and heparin onto titanium has been
      studied in the absence and presence of bovine serum albumin (BSA). Isotherm data
      (0.02 M calcium acetate, pH 6.8) have shown that BSA in solution and BSA-coated
      titanium result in decreased adsorption for both C4S and heparin. For the BSA in
      solution data, C4S/heparin and BSA may compete for the same sites on the titanium
      surface via calcium ions, or alternatively in the case of heparin, complexes of
      heparin and BSA form in solution, leading to less binding due to steric effects.
      Evidence of an interaction between heparin and BSA in solution has been shown in
      this study, there being negligible interaction between C4S and BSA. BSA
      adsorption from solution investigated in the presence of C4S/heparin decreases
      with increasing C4S/heparin solution concentration. This may be due to a
      glycosaminoglycan (GAG) induced conformational change of BSA from a compact to an
      extended structure. The decreased adsorption onto BSA-coated titanium may be due
      to masking of the GAG binding sites, this effect being greater for C4S.
      Desorption of BSA from the pre-coated titanium in the presence of C4S and heparin
      is <10% and <30% respectively, indicating that BSA is strongly bound to the
      titanium surface.

PMID- 9247351
TI  - Comparison of the porosity of hand-mixed and capsulated glass-ionomer luting
      cements.
AB  - The strength of dental glass-ionomer cements will be influenced by defects
      present within its structure. This study measured the surface area porosity,
      percentage surface area porosity, and mean surface area of small bubbles (<0.01
      mm2) and the surface area porosity, percentage surface area porosity and diameter
      of large bubbles within 40-microm-thick layers of four cements, using image
      analysis software. Two hand-mixed cements (Fuji I and KetacCem) and two
      capsulated cements (Fuji Cap I and KetacCem Maxicap) were viewed under
      transmitted light at x117.6 magnification. For each selected area (64.75 mm2) of
      each cement sample, five independent measurements were made of each of these
      parameters. Analysis of variance (ANOVA) indicated that there were no significant
      differences between the four cements in the small bubble parameters measured,
      whilst there were significant differences in the surface area porosity,
      percentage surface area porosity and diameter of the large bubbles. It was
      concluded that the hand-mixed cements tested had a greater number of larger
      diameter bubbles compared with the capsulated cements.

PMID- 9247352
TI  - Acrylic bone cement induces the production of free radicals by cultured human
      fibroblasts.
AB  - Arthroplasty with poly(methyl methacrylate) (PMMA) bone cement induces late
      loosening phenomena that compromise the prosthetic stability. As free radicals
      are inflammatory mediators and cytotoxic, it seemed useful to investigate whether
      PMMA induces the liberation of free radicals and/or cytotoxicity. The effect of
      PMMA interaction on cultured human fibroblasts was accessed by the cell viability
      test (MTT), and by the measurement of lipoperoxides in the incubation medium. The
      incubation with the medium exposed to PMMA induced a significant reduction in the
      viability and a significant increase in lipoperoxide liberation (vs control).
      These data suggest that PMMA is cytotoxic. This effect seems to be mediated by
      lipoperoxide and possibly by other free radicals, and may explain the peri
      implant loosening phenomena that compromise the prosthetic stability.

PMID- 9247354
TI  - Heparan sulfate isomers in cerebral arteries of Japanese women with aging and
      with atherosclerosis--heparitinase and high-performance liquid chromatography
      determinations.
AB  - Composition of heparan sulfate (HS) isomers from unaffected and atherosclerotic
      cerebral arteries (isolated by autopsy) of Japanese women, of various ages, was
      studied. HS isomers were separated as disaccharide units by high-performance
      liquid chromatography after degeneration with HS and heparin lyases. Heparitinase
      facilitated differentiation of eight unsaturated disaccharides (deltaDi-S(HS)) of
      vascular HS isomers. The HS isomers in the cerebral arteries consisted of
      approximately half the total glycosaminoglycans (GAGs). Both HS (and GAGs) tended
      to increase with the processes of aging but decreased with the advancing
      development of atherosclerosis. The HS isomers consisted of a higher proportion
      of non-sulfated disaccharide, about 2/3 of the total HS, followed by mono
      sulfated and bis-sulfated saccharides; in addition, heparin existed, albeit in
      minute amounts. The proportion of deltaDi-S(HS) rich in sulfate compared with HS
      isomers tended to increase with aging but most decreased during formation of the
      atheroma. Putative functions of HS isomers in cerebral arteries are discussed,
      based on the characteristic distribution of HS components.

PMID- 9247353
TI  - Potential involvement of type II phospholipase A2 in atherosclerosis.

PMID- 9247355
TI  - High fat, high cholesterol diets alter low density lipoprotein size and binding
      affinity in monkeys.
AB  - The purpose of this study was to examine the effects of various dietary fats on
      low density lipoprotein (LDL) binding in an in vitro system where receptor number
      is not regulated. Cynomolgus monkeys were fed diets containing 37% of energy from
      fat, with various degrees of saturation, and 0.4 mg/kcal cholesterol or low-fat
      (13% of energy), low cholesterol (0.03 mg/kcal) chow. Plasma LDL was isolated
      after 16 weeks. The fatty acid composition of LDL showed enrichment corresponding
      to the dietary fats consumed, and the high fat, high cholesterol diets produced
      marked hypercholesterolemia compared to chow feeding. Of those fed the high fat
      diets, monkeys fed the fish oil diet had the highest LDL cholesterol
      concentrations, 13.25 +/- 0.77 mmol/l, while those fed the safflower oil diet had
      the lowest, 7.51 +/- 3.31. LDL from chow fed monkeys had the lowest binding
      affinity; the Kd was 26.2 +/- 8.7 microg/ml, nearly twice that of the high fat
      diets (P = 0.003). No significant differences in binding were found between the
      different high fat diets, although there was a trend toward lower affinity in the
      diets enriched in polyunsaturated fat. LDL size was affected by diet with chow
      fed monkeys having the smallest average LDL, 259.3 +/- 1.7 A compared to the
      other groups (P = 0.03). Monkeys fed the fish oil diet tended to have smaller
      LDL, but this was not significantly different from the other high fat diets.
      Binding affinity was correlated with LDL size, r = 0.54, P < 0.01. LDL
      composition, as measured by apo B/cholesterol ratio, was altered by feeding a
      high fat, high cholesterol diet. The ratio was reduced in the LDL samples from
      monkeys fed the high fat diets compared to those fed chow, but this ratio was not
      significantly correlated with binding. Thus, it appears that increasing dietary
      fat and cholesterol intake increases LDL size and binding affinity, such that LDL
      metabolism may be altered independently from effects on receptor number; the type
      of dietary fat does not seem to influence this process when fat and cholesterol
      content is very high.

PMID- 9247356
TI  - Native and gamma radiolysis-oxidized lipoprotein(a) increase the adhesiveness of
      rabbit aortic endothelium.
AB  - Accumulation of monocyte-derived foam cells in the arterial intima is a major
      event in the development of atherogenesis. We have examined whether native and
      oxidized lipoprotein(a) (Lp(a)) can induce adhesion of monocytic cells to aortic
      endothelium. The extensive oxidation of paired samples of Lp(a) and low-density
      lipoprotein (LDL) was achieved by O2.-/OH. free radicals produced by gamma
      radiolysis of water, leading to similar values for the formation of peroxidation
      markers (conjugated dienes, TBARS, 8-epi-PGF2alpha) for both Lp(a) and LDL.
      Rabbit aortic segments were incubated for 5 h in the presence of equimolar
      concentrations of native and oxidized preparations of Lp(a) and LDL (125 micromol
      cholesterol/l, corresponding to 40 and 30 mg protein/l for Lp(a) and LDL,
      respectively). The aortic segments were incubated with rhodamin-isothiocyanate
      labeled U937 monocytic cells for 30 min and cell adhesion was quantified by
      fluorescent microscopy. Native Lp(a), and to a larger extent oxidized Lp(a),
      significantly increased U937 cell adhesion by 2.3 and 2.7 fold compared to
      controls (P < 0.005 and P < 0.001, respectively). Monocytic cell adhesion was
      also increased by native LDL (1.6 fold, P < 0.005), and to a greater extent by
      oxidized LDL (2.3 fold, P < 0.001). Thus native Lp(a) enhances the adhesive
      properties of the arterial endothelium which may account for its proatherogenic
      action. Furthermore, our results show that oxidized Lp(a), as well as oxidized
      LDL, are potent stimuli of monocyte adhesion to endothelial cells.

PMID- 9247357
TI  - The effect of the aged garlic extract, 'Kyolic', on the development of
      experimental atherosclerosis.
AB  - The aged garlic extract 'Kyolic' lowers serum cholesterol levels in humans and
      experimental animals and thus is presumed to have a protective effect against
      atherosclerosis. However, to date no studies have examined the effect of this
      substance on the actual development of the disease. In the present study, the
      right carotid artery of 24 rabbits was de-endothelialized by balloon
      catheterisation in order to produce a myointimal thickening. After 2 weeks the
      rabbits were randomly assigned to four groups: Group I received a standard diet;
      Group II received the standard diet supplemented with 800 microl/kg body
      weight/day 'Kyolic'; Group III received a 1% cholesterol supplemented standard
      diet; and Group IV received a 1% cholesterol supplemented standard diet plus
      'Kyolic'. After 6 weeks, the cholesterol diet caused a 6-fold increase in serum
      cholesterol level (Group III; 6.4 +/- 0.6 mmol/l) compared to normal diet (Group
      I; 1.2 +/- 0.4 mmol/l) (P < 0.05) with only a minor, non-significant reduction
      seen by the addition of 'Kyolic' (Group IV; 6.2 +/- 0.7 mmol/l). Group III
      rabbits developed fatty streak lesions covering approximately 70 +/- 8% of the
      surface area of the thoracic aorta, which was significantly reduced to 25 +/- 3%
      in the 'Kyolic'-treated Group IV. No lesions were present in Groups I and II. The
      hypercholesterolaemic diet caused an increase in aortic arch cholesterol (2.1 +/-
      0.1 mg cholesterol/g tissue) which was significantly reduced by 'Kyolic'
      supplementation (1.7 +/- 0.2 mg cholesterol/g tissue) (P < 0.05). 'Kyolic'
      significantly inhibited the development of thickened, lipid-filled lesions in the
      pre-formed neointimas produced by balloon-catheter injury of the right carotid
      artery in cholesterol-fed rabbits (intima as percent of artery wall, Group III
      42.6 +/- 6.5% versus Group IV 23.8 +/- 2.3%, P < 0.01), but had little effect in
      rabbits on a standard diet (Group II 18.4 +/- 5.0% versus Group I 16.7 +/- 2.0%).
      In vitro studies showed that 'Kyolic' has a direct effect on inhibition of smooth
      muscle proliferation. In conclusion, 'Kyolic' treatment reduces fatty streak
      development, vessel wall cholesterol accumulation and the development of fibro
      fatty plaques in neointimas of cholesterol-fed rabbits, thus providing protection
      against the onset of atherosclerosis.

PMID- 9247358
TI  - Characteristics of coronary artery disease and lipoprotein abnormalities in
      patients with heterozygous familial hypercholesterolemia associated with diabetes
      mellitus or impaired glucose tolerance.
AB  - Familial hypercholesterolemia (FH) is a genetic disorder characterized by high
      levels of serum low density lipoprotein (LDL) cholesterol and premature coronary
      atherosclerosis. In order to elucidate the influence of abnormal glucose
      metabolism on the development of coronary artery disease (CAD) in FH patients, we
      examined the prevalence of CAD and characteristics of lipoprotein abnormalities
      in patients with heterozygous FH who were accompanied by diabetes mellitus (DM)
      or impaired glucose tolerance (IGT). The subjects of the present study were 150
      patients with heterozygous FH, all over 40 years of age. Oral glucose tolerance
      tests demonstrated that 15 patients had DM and 27 had IGT. The combination of DM
      or IGT with FH was associated with a further increase in the prevalence of CAD
      (DM:IGT:normal glucose tolerance (N), 87:59:43%). Furthermore, the prevalence of
      the stenoses in the distal coronary arteries was significantly higher in the DM
      group than in the N group, while there was no significant difference in the
      prevalence of proximal and middle lesions. Serum triglyceride levels were
      significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM
      versus N group; P < 0.01, IGT versus N group), while total cholesterol levels
      were not significantly different. When lipoproteins were analyzed by
      polyacrylamide gel electrophoresis, the frequency of midband appearance, which
      implies an increase in remnant lipoproteins, was significantly higher in the DM
      and IGT groups than in the N group (DM:IGT:N, 87:72:29%, P < 0.01, DM versus N
      group; P < 0.01, IGT versus N group). Ultracentrifugation analysis of
      lipoproteins revealed that intermediate density lipoprotein cholesterol was
      increased in DM and IGT groups compared with the N group. These data suggest that
      abnormal glucose metabolism may accelerate the development of CAD in FH patients
      due to an increase in atherogenic remnant lipoproteins in addition to high
      concentration of LDL. Special attention should be paid in the treatment of FH
      patients with impaired glucose metabolism, to avoid the advancement of coronary
      atherosclerosis.

PMID- 9247359
TI  - Inhibition of smooth muscle cell migration by the p21 cyclin-dependent kinase
      inhibitor (Cip1).
AB  - In vascular smooth muscle cells (SMCs), proliferation and migration contribute to
      lesion formation after arterial injury. In the cell cycle, several cyclin
      dependent kinases (cdks) inhibitors are implicated in the regulating of cyclin
      cdk activity such as p21Cip1, p16Ink4 and p27Kip1. Although Cip1 inhibits SMC
      proliferation, its effects on SMC migration are unknown. To test the hypothesis
      that Cip1 inhibits SMCs migration and proliferation, we transfected the Cip1 gene
      into a strain of rabbit aortic SMCs (SM3 cells). Both the spreading and the
      attachment of Cip1-transfected SM3 cells to extracellular matrices (ECMs) were
      inhibited compared to that of vector-transfected cells. In the modified Boyden's
      chamber assay the effect of fibronectin on the migratory activity of Cip1
      transfected SM3 cells was significantly less than that of vector transfected
      cells in response to PDGF-BB. These data suggested that Cip1 inhibited both the
      migration and proliferation of SMC.

PMID- 9247360
TI  - Modulation of arterial thrombosis tendency in rats by vitamin K and its side
      chains.
AB  - Vitamin K is involved in the biosynthesis of a number of blood coagulation
      factors and bone proteins. It has been suggested that the vitamin K requirement
      of bone tissue is higher than that of the liver. Here we report that in rats very
      high doses of vitamin K affected neither the blood coagulation characteristics
      nor the blood platelet aggregation rate. This was observed for both phylloquinone
      and menaquinone-4. Both vitamers were also tested for their effects on the
      arterial thrombosis tendency in the rat aorta loop model. The mean obstruction
      times were prolonged at a high intake of menaquinone-4 (250 mg/kg body
      weight/day), and shortened after a similarly high phylloquinone regimen. Since
      (a) both vitamers only differ in their aliphatic side chains; and (b) a similar
      trend was observed after administration of phytol and geranylgeraniol, we
      conclude that the modulation of the arterial thrombosis tendency is accomplished
      by the side chain of vitamin K.

PMID- 9247361
TI  - Dietary flax seed in prevention of hypercholesterolemic atherosclerosis.
AB  - Oxygen free radicals (OFRs) have been implicated in the development of
      hypercholesterolemic atherosclerosis. Flax seed is the richest source of omega-3
      fatty acid and lignans. omega-3 Fatty acid suppresses the production of
      interleukin-1 (IL-1), tumor necrosis factor (TNF) and leukotriene B4 (LTB4), and
      of OFRs by polymorphonuclear leukocytes (PMNLs) and monocytes. Lignans possess
      anti-platelet activating factor (PAF) activity and are antioxidant. PAF, IL-1,
      TNF and LTB4 are known to stimulate PMNLs to produce OFRs. Flaxseed would,
      therefore, reduce the levels of OFRs and hence would prevent the development of
      hypercholesterolemic atherosclerosis. The effects of dietary flax seed on a high
      cholesterol diet induced atherosclerosis, lipid profile and OFR-producing
      activity of PMNLs (PMNL-CL) were investigated in rabbits. The rabbits were
      divided into 4 groups: group I, control; group II, flax seed diet (7.5 g/kg
      daily, orally); group III, 1% cholesterol diet; and group IV, same as group III
      but received flax seed (7.5 g/kg daily, orally). Blood samples were collected
      before and after 4 and 8 weeks on their respective diets for biochemical
      measurements and aortae were removed at the end of 8 weeks for estimation of
      atherosclerotic changes. The high cholesterol diet increased the serum level of
      total cholesterol (TC) and PMNL-CL without altering the levels of serum
      triglycerides (TG). These changes were associated with a marked development of
      atherosclerosis in the aorta. Flax seed reduced the development of aortic
      atherosclerosis by 46% and reduced the PMNL-CL without significantly lowering the
      serum cholesterol. Flax seed in normocholesterolemic rabbits increased serum
      total cholesterol and decreased PMNL-CL without significantly affecting the serum
      TG. Modest dietary flax seed supplementation is effective in reducing
      hypercholesterolemic atherosclerosis markedly without lowering serum cholesterol.
      Its effectiveness against hypercholesterolemic atherosclerosis could be due to
      suppression of enhanced production of OFRs by PMNLs in hypercholesterolemia.
      Dietary flax seed supplementation could, therefore, prevent hypercholesterolemia
      related heart attack and strokes.

PMID- 9247362
TI  - Apolipoprotein(a) isoforms and coronary heart disease in men: a nested case
      control study.
AB  - The objective of the present study was to examine the possible associations
      between low molecular weight (LMW) apolipoprotein(a) (apo(a)) isoforms
      (F,B,S1,S2) and coronary heart disease (CHD). We conducted a nested case-control
      (prospective) study of five cohorts of white men: The 1936 cohort (baseline 1976,
      n = 548) and four cohorts from MONICA I born in 1923 (n = 463), 1933 (n = 491),
      1943 (n = 504) and 1953 (n = 448) studied at baseline in 1983. At follow up in
      1991, 52 subjects had developed a first myocardial infarction and 22 had been
      hospitalized with angina pectoris. Plasma samples obtained at baseline were
      stored frozen until 1993-94, when case samples (n = 74) were analyzed together
      with samples from matched (disease free) controls (n = 190). In a statistical
      model (conditional logistic regression) including all age groups, cholesterol (or
      apo B) level (P < 0.01), systolic blood pressure (P = 0.05) and smoking (P =
      0.02) predicted CHD. In the statistical model Lp(a) interacted significantly with
      age (OR = 5.7; 95% CI: 1.4-23.6; P = 0.016), and high Lp(a) (over 45 mg/dl) was
      associated with significantly increased risk in subjects under 60 years (OR =
      3.82; 95% CI: 1.47-9.96), but not in older men (OR = 0.67; 95% CI: 0.235-1.89).
      Therefore, we studied the impact of Lp(a)/apo(a) and other variables in subjects
      who had been under 60 years when they became cases. Among the younger subjects
      the presence of LMW apo(a) isoforms significantly predicted the development of
      CHD (OR = 3.83; 95% CI: 1.18-12.4). The increased risk pertained to high Lp(a)
      (above versus below 45 mg/dl: OR = 3.68; 95% CI: 1.03-13.10), and to Lp(a)
      concentrations when entered into the model as a continuous variable (P = 0.04).
      Cholesterol or apo B (P < 0.01), smoking (P = 0.02), systolic blood pressure (P =
      0.05) and low alcohol consumption (under nine drinks/week) (P = 0.04) were also
      significant predictors of CHD. We conclude that LMW apo(a) isoforms are
      significantly associated with increased risk of CHD in men under 60 years.

PMID- 9247363
TI  - Pseudo type III dyslipoproteinemia is associated with normal fibroblast
      lipoprotein receptor activity.
AB  - Pseudo type III (PT-III) dyslipoproteinemia is characterized by a plasma
      accumulation of triglyceride-rich lipoproteins (TRL) and their remnants. It
      mimics type III, but its etiology can not be ascribed to a genetic apo E defect.
      In order to determine whether PT-III is associated with a genetic lipoprotein
      receptor abnormality, we have measured (in cultured fibroblasts from affected and
      nonaffected individuals) the in vitro activity of three lipoprotein receptors
      which are implicated in the catabolism of TRL, namely the low-density lipoprotein
      receptor (LDL-R), the lipoprotein receptor-related protein (LRP) and the
      lipolysis-stimulated receptor (LSR). Specific cell association and degradation of
      125I-LDL by LDL-R-upregulated PT-III fibroblasts was not significantly different
      from that of control cells (103 +/- 10% and 98 +/- 17% of controls; 20 microg/ml
      125I-LDL). Specific cell association and degradation of rabbit 125I-beta-VLDL was
      also not significantly different. LRP activity was assessed by measuring the
      ability of PT-III and control cells to bind three different LRP ligands:
      activated alpha2-macroglobulin (alpha2M-MA), lactoferrin and apo E-enriched
      rabbit beta-VLDL. No significant differences were observed (24.0 +/- 2.1 vs. 23.4
      +/- 5.7 fmol/mg for 5 nM of 125I-alpha2M-MA; 4.8 +/- 0.3 vs. 5.2 +/- 1.3
      microg/mg for 20 microg/ml of 125I-lactoferrin; 319.4 +/- 51.2 vs. 309.5 +/- 23.2
      ng/mg for 5 microg/ml of 125I-beta-VLDL, PT-III vs. control, respectively). LSR
      activity, as assessed by the cell association or degradation of 125I-LDL by
      fibroblasts in the presence of 0.5 mM oleate and human leptin, was also not
      different. No evidence was obtained for deficient cellular recognition of PT-III
      TRL (d < 1.006 g/ml) by normal human fibroblasts or mouse macrophages. These
      results suggest that PT-III dyslipoproteinemia is not due to an accumulation in
      plasma of poorly recognized TRL, nor due to a genetic defect in LDL-R, LRP or
      LSR.

PMID- 9247364
TI  - Smokeless tobacco use and atherosclerosis: an ultrasonographic investigation of
      carotid intima media thickness in healthy middle-aged men.
AB  - There is well-documented evidence of accelerated atherosclerosis in smokers but
      the mechanisms still remain unclear. The relationship to the use of smokeless
      tobacco, involving high exposure to nicotine, have not been evaluated before. The
      possible role of nicotine was investigated in a clinical study of the intima
      media thickness in the carotid artery of 143 healthy, middle-aged men (35-60
      years old) with different tobacco consumption habits. B-mode ultrasonography was
      performed and biochemical risk factors for cardiovascular disease (serum lipids,
      serum lipoproteins and plasma fibrinogen) were determined. Long term smokeless
      tobacco users (n = 28) did not differ significantly from never-users (n = 40)
      regarding bulb intima media thickness (0.80 +/- 0.13 versus 0.78 +/- 0.12 mm) or
      common carotid intima media thickness (0.67 +/- 0.11 versus 0.68 +/- 0.11 mm),
      whereas smokers (n = 29) had significantly increased wall measurements (bulb 0.87
      +/- 0.19, P = 0.002 common carotid 0.74 +/- 0.13, P = 0.03) compared to never
      users. Only in smokers were biochemical risk factors significantly altered
      towards an elevated risk. Significant effects of interaction of smoking and
      increased s-cholesterol levels on carotid intima media thickness were also found.
      Smokeless tobacco users showed similar tendencies, but without definite
      statistical significance. On the basis of these data, it appears most likely that
      the increased occurrence of atherosclerosis in smokers is caused by other
      components of tobacco smoke than nicotine.

PMID- 9247365
TI  - The 677C-->T mutation in the methylenetetrahydrofolate reductase gene:
      associations with plasma total homocysteine levels and risk of coronary
      atherosclerotic disease.
AB  - Homozygosity for a 677C-->T mutation at the locus that codes for 5,10
      methylenetetrahydrofolate reductase (MTHFR), a folate-dependent crucial enzyme in
      homocysteine metabolism, may render the enzyme thermolabile and less active and
      has been associated with increased levels of plasma total homocysteine (tHcy). We
      assessed whether this mutation was associated with increased risk of coronary
      atherosclerosis and plasma levels of tHcy and furthermore studied whether folate
      status would modify the associations. Data were collected from subjects with
      substantial coronary atherosclerosis (> or = 90% occlusion in one and > or = 40%
      occlusion in a second coronary artery, referred to as cases, n = 131) or
      virtually no coronary narrowing (referred to as coronary controls, n = 87) and
      from a population-based control group (n = 100), all residing in the Rotterdam
      area, The Netherlands. Both males and females, aged 25-65 years were studied. The
      frequency of homozygosity for the mutation (+/+) in cases (10.0%) did not
      significantly differ statistically from that observed in coronary controls
      (11.5%, P = 0.71), population-based controls (7.0%, P = 0.43), or combined
      control groups (9.1%, P = 0.80). In the overall group (as well as in the three
      subgroups), plasma tHcy levels, fasting and to a lesser extent after a methionine
      loading test, were higher in +/+ subjects than in homozygous normal subjects (-/
      ), whereas heterozygous subjects (+/-) had intermediate levels (Ptrend = 0.001).
      The +/+ subjects with erythrocyte folate levels < 790 nmol/l (population median)
      had a 77%, (95% CI, 27-144%) higher geometric mean fasting tHcy (21.4,
      micromol/l) than those with higher erythrocyte folate (12.1 micromol/l). The odds
      ratio (OR) of coronary atherosclerosis for +/+ subjects, with +/- and -/-
      subjects as the reference group, in analyses with combined control groups, was
      1.1 (95% CI, 0.5-2.4). The ORs were 2.2 (95% CI, 0.7-6.8) and 0.6 (95% CI, 0.2
      1.7) among subjects with low and high folate levels, respectively. Our study
      indicates that homozygosity for the 677C-->T MTHFR mutation, especially in
      combination with low folate status, predisposes to high plasma levels of fasting
      tHcy. However, homozygosity for this mutation, whether or not in combination with
      low folate status, was not associated with increased risk of coronary artery
      disease.

PMID- 9247366
TI  - Is arterial remodeling truly a compensatory biological reaction? A mechanical
      deformation hypothesis.
AB  - It has been recognized that arterial enlargement occurs in relation to the
      formation of atherosclerotic plaque. Previous studies on arterial remodeling have
      disregarded the role of mechanical deformation and have suggested that
      compensatory mechanisms occur to maintain arterial flow. We postulated that
      primary atherosclerotic enlargement and mechanical deformation are the
      predominant causes of the arterial remodeling. This hypothesis better explains
      the morphological changes without suggesting additional biological reactions.

PMID- 9247368
TI  - Summary of notifiable diseases, United States, 1993.

PMID- 9247367
TI  - Intermediate density lipoprotein cholesterol as the best lipoprotein predictor of
      atherosclerosis severity in the Watanabe Heritable Hyperlipidemic rabbit.

PMID- 9247369
TI  - The Social Influence of Confidence in Group Decision Making
AB  - This study investigates the relation between an individual's self-reported
      confidence and his or her influence within a freely interacting group. Each
      participant chose responses and provided confidence assessments for choice items
      of a variety of task types, first as an individual and a second time as a member
      of a pentad, a member of a dyad, or an individual. The influence of a particular
      faction within a group was greater if its members were more confident. A
      participant's response accuracy was related to both greater confidence and
      greater influence to the extent that the task fell on the intellective end of the
      intellective-judgmental continuum of task types. As a result, the extent to which
      group members' confidence predicted their influence was also greatest on
      intellective rather than judgmental tasks. Results further illustrate that adding
      group members to work on a problem may increase overconfidence on judgmental
      tasks but decrease overconfidence on intellective tasks.

PMID- 9247370
TI  - Extending the Benefits of Recategorization: Evaluations, Self-Disclosure, and
      Helping
AB  - The Common Ingroup Identity Model proposes that if members of different groups
      conceive of themselves more as a single group rather than as two separate groups,
      intergroup bias will be reduced through processes involving pro-ingroup
      favoritism. The present research extended work on this model by investigating the
      effects of recategorization on intergroup behavior, specifically helping and self
      disclosure, as well as evaluations. Participants first worked as members of two
      three-person groups, and then the two groups interacted under conditions designed
      to enhance a two-group representation or recategorization with an inclusive one
      group representation. As expected, the manipulation of the intergroup contact
      situation that created stronger impressions of one group reduced intergroup bias
      in evaluations, self-disclosure, and helping. Furthermore, ratings of the extent
      to which the six participants felt like one group mediated the reduction in bias,
      particularly for evaluative bias. Conditions facilitating the generalization of
      the benefits of recategorization to group members not present and to other groups
      are considered.

PMID- 9247371
TI  - Temporal Adjustments in the Evaluation of Events: The "Rosy View"
AB  - In a series of three investigations we examined people's anticipation of, actual
      experiences in, and subsequent recollection of meaningful life events: a trip to
      Europe, a Thanksgiving vacation, and a 3-week bicycle trip in California. The
      results of all three studies supported the hypothesis that people's expectations
      of personal events are more positive than their actual experience during the
      event itself, and their subsequent recollection of that event is more positive
      than the actual experience. The "rosy view" phenomenon is associated with an
      increase in the number of negative thoughts during the event which seem to be
      caused by distractions, disappointment, and a less positive view of the self.
      However, these effects are short-lived; within days after the event, people have
      much more positive evaluations of the event. We discuss alternative
      interpretations for our findings and implications for group and organizational
      settings.

PMID- 9247372
TI  - The leader-follower connection.

PMID- 9247373
TI  - Avoiding alendronate-related esophageal irritation.

PMID- 9247377
TI  - Using the Faces scale to assess pain.

PMID- 9247378
TI  - Considerations in reporting elder abuse.

PMID- 9247379
TI  - Understanding the devastation of AIDS.
AB  - A patient admitted to your unit this morning presents a dauntingly complex
      clinical picture. Maria DeJesus, 34 years old, has HIV infection, which
      progressed to AIDS last year with an episode of Pneumocystis carinii pneumonia.
      She's also experienced recurrent vaginal and esophageal candidiasis and
      cryptococcal meningitis, and her more recent history includes peripheral
      neuropathy, causing pain and numbness, as well as cognitive and motor function
      problems. Her admission was prompted by diarrhea that has persisted despite
      outpatient treatment. To provide the best care for patients like Ms. DeJesus, you
      need to understand HIV infection and the diseases associated with it. Yet that's
      a challenging task, given that the possible manifestations of advanced infection
      are so many and varied. Though your approach to care is holistic, you may find it
      helpful to consider the numerous facets of the patient's illness individually. In
      the following pages, we'll examine how HIV enters the body, infects immune cells,
      and eventually cripples the immune system. We'll look at some of the more common
      opportunistic infections preying on people with HIV. And we'll explore the less
      well-charted territory of complications attributed to HIV infection of the
      central and peripheral nervous systems.

PMID- 9247380
TI  - Essential elements of ostomy care.

PMID- 9247381
TI  - Emergency! Severe preeclampsia.

PMID- 9247382
TI  - Team building in a health care setting.

PMID- 9247383
TI  - When alcoholism hits home.

PMID- 9247384
TI  - Why must nurses risk their careers for safe care?

PMID- 9247385
TI  - Child psychiatry comes of age: growing sophistication, evolving strategies.

PMID- 9247386
TI  - Clinical Genetics, II. Huntington's disease: from the gene to pathophysiology.

PMID- 9247387
TI  - Anterior cingulate gyrus volume and glucose metabolism in autistic disorder.
AB  - OBJECTIVE: This study reports the first paired measurements of glucose metabolism
      and volume of the anterior cingulate gyrus in autism. METHOD: Magnetic resonance
      imaging (MRI) and positron emission tomography (PET) scans of seven high
      functioning autistic patients and seven sex- and age-matched normal volunteers
      were coregistered. After the anterior cingulate gyri were outlined on the MRI
      images, the volumes of the structures were measured and corrected for brain
      volume. The volumes were then applied to the PET images and metabolic maps were
      obtained. RESULTS: Right anterior cingulate area 24' was significantly smaller in
      relative volume, and both area 24 and area 24' were metabolically less active, in
      the autistic patients than in the normal subjects. CONCLUSIONS: Autism may be
      characterized by structural and functional alterations in the anterior cingulate
      gyrus.

PMID- 9247388
TI  - An MRI study of the corpus callosum in autism.
AB  - OBJECTIVE: The purpose of this study was to examine the size of subregions of the
      corpus callosum in autistic individuals. METHOD: The areas of three subregions
      (anterior, body, and posterior) of the corpus callosum were examined on
      midsagittal magnetic resonance images of 35 autistic subjects whose mean age was
      18 years and 36 healthy comparison subjects matched on age and IQ. RESULTS: After
      controlling for total brain volume, gender, and performance IQ, the authors
      detected a significantly smaller size of the body and posterior subregions of the
      corpus callosum in the autistic individuals. CONCLUSIONS: In the context of
      recent reports of increased brain size in autism, several possible mechanisms are
      considered in exploring the significance of a smaller relative size of the corpus
      callosum in autism.

PMID- 9247389
TI  - Relative efficacy of haloperidol and pimozide in children and adolescents with
      Tourette's disorder.
AB  - OBJECTIVE: The authors evaluated the relative efficacy and safety of pimozide and
      haloperidol in the treatment of Gilles de la Tourette's syndrome in children and
      adolescents. METHOD: A double-blind, 24-week, placebo-controlled double crossover
      study of equivalent dose formulations of haloperidol and pimozide was conducted
      with 22 subjects, aged 7-16 years, with Tourette's disorder who were randomly
      assigned to first one active drug treatment and then the other. Biweekly
      assessment and flexible dose titration mimicked clinical practice. The primary
      outcome variable was total score on the Tourette Syndrome Global Scale. Final
      outcome was determined after 6 weeks of each treatment (placebo, pimozide,
      haloperidol), with a 2-week placebo baseline period and intervening 2-week
      placebo washout periods between treatments. RESULTS: Pimozide proved
      significantly different from placebo in affecting the primary outcome variable,
      whereas haloperidol failed to have a significant effect. Haloperidol exhibited a
      threefold higher frequency of serious side effects and significantly greater
      extrapyramidal symptoms relative to pimozide. Haloperidol-associated treatment
      limiting adverse events were experienced by 41% of the patients. The therapeutic
      doses of pimozide and haloperidol were equivalent (mean = 3.4 mg/day, SD = 1.6,
      and mean = 3.5 mg/day, SD = 2.2, respectively). CONCLUSIONS: At equivalent doses,
      pimozide is superior to haloperidol for controlling symptoms of Tourette's
      disorder in children and adolescents.

PMID- 9247390
TI  - Low glucose metabolism during brain stimulation in older Down's syndrome subjects
      at risk for Alzheimer's disease prior to dementia.
AB  - OBJECTIVE: Down's syndrome is characterized by the genetically programmed
      accumulation of substantial Alzheimer's disease neuropathology after age 40 and
      the development of early dementia years later, providing a unique human model to
      investigate the preclinical phases of Alzheimer's disease. Older nondemented
      adults with Down's syndrome show normal rates of regional cerebral glucose
      metabolism at rest before the onset of dementia, indicating that their neurons
      maintain function at rest. The authors hypothesized that an audiovisual
      stimulation paradigm, acting as a stress test, would reveal abnormalities in
      cerebral glucose metabolism before dementia in the neocortical parietal and
      temporal areas most vulnerable to Alzheimer's disease. METHOD: Regional cerebral
      glucose metabolism was assessed by means of positron emission tomography (PET)
      with [18F]fluorodeoxyglucose in eight younger (mean age = 35 years, SD = 2) and
      eight older (mean age = 50, SD = 7) healthy, nondemented adults with trisomy 21
      Down's syndrome. PET scans were performed at rest and during audiovisual
      stimulation in the same scanning session. Levels of general intellectual
      functioning and compliance were similar in the two groups. RESULTS: At rest the
      two groups showed no difference in glucose metabolism in any cerebral region. In
      contrast, during audiovisual stimulation the older subjects with Down's syndrome
      had significantly lower glucose metabolic rates in the parietal and temporal
      cortical areas. CONCLUSIONS: Abnormalities in cerebral metabolism during
      stimulation appeared in the first cortical regions typically affected in
      Alzheimer's disease. These results indicate that a stress test paradigm can
      detect metabolic abnormalities in the preclinical stages of Alzheimer's disease
      despite normal cerebral metabolism at rest.

PMID- 9247391
TI  - Durable power of attorney and informed consent with Alzheimer's disease patients:
      a clinical study.
AB  - OBJECTIVE: Experience with a new surrogate consent system for patients with
      Alzheimer's disease is reviewed. It was hypothesized that as patients' cognitive
      status deteriorated, surrogate consent through a durable power of attorney would
      become necessary to facilitate continued involvement in clinical research.
      METHOD: The authors retrospectively reviewed the charts of inpatients with
      Alzheimer's disease who participated in research between January 1989 and
      December 1994 at the Geriatric Psychiatry Unit of the National Institute of
      Mental Health. Seventy-nine patients were included. The main outcome measures
      were the Clinical Dementia Rating, Global Deterioration Scale for primary
      degenerative dementia, and Mini-Mental State. RESULTS: Most patients were in the
      mild-to-moderate stage of the illness when they chose to participate in research
      and assign a durable power of attorney (96% scored 2 or less on the Clinical
      Dementia Rating, and 92% scored 5 or less on the Global Deterioration Scale). On
      average, the subjects participated in 3.8 (SD = 2.6) studies. For 35 patients
      with multiple admissions over this period (average = 3.1 years), scores on the
      Clinical Dementia Rating and Global Deterioration Scale declined by 1.0 and 1.5
      points, respectively. CONCLUSIONS: The durable power of attorney allows research
      participation for subjects with Alzheimer's disease at all stages. The linchpin
      is assignment of a durable power of attorney in the early-to-moderate stage of
      Alzheimer's disease, before subjects lose the capacity to give informed consent.
      This approach could also be adapted to patients with cognitive decline due to
      other debilitating diseases.

PMID- 9247392
TI  - Startle reflex abnormalities in women with sexual assault-related posttraumatic
      stress disorder.
AB  - OBJECTIVE: This investigation was designed to assess the acoustic startle
      response in treatment-seeking women with sexual assault-related posttraumatic
      stress disorder (PTSD). METHOD: Thirteen patients with sexual assault-related
      PTSD and 16 healthy female comparison subjects were recruited for participation
      in the study. Each patient met the full criteria for PTSD according to the
      Structured Clinical Interview for DSM-III-R. All subjects in the study were right
      handed. The acoustic stimuli were bursts of white noise (92 dB and 102 dB) with a
      nearly instantaneous onset delivered binaurally through headphones. RESULTS: The
      magnitude of the startle response (eye blink) to the first stimulus was
      asymmetrically distributed in the PTSD patients but not in the comparison
      subjects: it was greater for the left eye than the right eye in the PTSD patients
      only. There was a differential asymmetry of startle response in the two subgroups
      of patients (recent PTSD and long-standing PTSD): the startle reflex was larger
      for the left eye than the right in the subgroup with recent PTSD but not in the
      group with long-standing PTSD. CONCLUSIONS: This study provides the first
      objective evidence of startle abnormalities in women with PTSD. The significantly
      greater startle responses for the left eye compared with the right in the PTSD
      subjects suggest a laterality effect. As suggested by the preclinical model of
      shock sensitization, it is possible that in a subgroup of individuals with PTSD,
      trauma may sensitize the startle reflex. This model may hold true in humans and
      is supported by the findings of greater startle response in the patients with
      recent-onset PTSD.

PMID- 9247393
TI  - Objective assessment of peritraumatic dissociation: psychophysiological
      indicators.
AB  - OBJECTIVE: The aims of this study were to investigate psychophysiological changes
      associated with peritraumatic dissociation in female victims of recent rape and
      to assess the relation between these changes and symptoms of posttraumatic stress
      disorder (PTSD). METHOD: Eighty-five rape victims were examined in a laboratory
      setting within 2 weeks after the rape, and measures of heart rate, skin
      conductance, and nonspecific movement were collected. Self-report indexes of
      reactions to the trauma and interviews to assess PTSD symptoms and peritraumatic
      dissociation were also completed. On the basis of their scores on the
      Peritraumatic Dissociation Index, the subjects were classified as having low or
      high levels of dissociation. RESULTS: Items from the index exhibited good
      internal consistency, and scores were approximately normally distributed.
      Individuals in the high peritraumatic dissociation group showed a significantly
      different pattern of physiological responses from those of the low dissociation
      group. In general, there was a suppression of autonomic physiological responses
      in the high dissociation group. This group also contained a larger proportion of
      subjects (94%) identified as meeting PTSD symptom criteria. Also, among the high
      dissociation subjects there was a discrepancy between self-reports of distress
      and objective physiological indicators of distress in the laboratory setting.
      CONCLUSIONS: The results provide preliminary support for the idea that there is a
      dissociative subtype of persons with PTSD symptoms who exhibit diminished
      physiological reactivity. The results also underscore the importance of assessing
      dissociative symptoms in trauma survivors.

PMID- 9247394
TI  - Response to hyperventilation and 5.5% CO2 inhalation of subjects with types of
      specific phobia, panic disorder, or no mental disorder.
AB  - OBJECTIVE: This study tested the hypothesis that compared to other DSM-IV
      specific phobia types, situational specific phobias have more in common with
      panic disorder and agoraphobia. METHOD: Responses to hyperventilation and CO2
      inhalation were compared across groups of patients with the four main DSM-IV
      specific phobia types, a group with panic disorder, and a group of comparison
      subjects with no anxiety disorder (N = 15 per group). RESULTS: Although these
      challenges have been shown previously to distinguish patients with panic disorder
      from other groups, no groups differed significantly in their responses to
      hyperventilation. In addition, whereas the patients with panic disorder responded
      more to the CO2 challenge than did the normal subjects, the specific phobia
      groups did not differ from one another or from the other groups on most measures.
      For the few CO2 measures on which specific phobia groups differed, patients with
      situational and natural environment phobias showed the greatest response.
      CONCLUSIONS: Overall, these findings provided only limited support for the
      hypothesis that situational specific phobias are related to panic disorder.

PMID- 9247395
TI  - Candidate gene study of eight GABAA receptor subunits in panic disorder.
AB  - OBJECTIVE: gamma-Aminobutyric acid type A (GABAA) receptor subunit genes are
      candidate genes for panic disorder. Benzodiazepine agonists acting at this
      receptor can suppress panic attacks, and both inverse agonists and antagonists
      can precipitate them. The human GABAA receptor subtypes are composed of various
      combinations of 13 subunits, each encoded by a unique gene. The authors tested
      eight of these subunits in a candidate gene linkage study of panic disorder.
      METHOD: In 21 U.S. and five Icelandic multiplex pedigrees of panic disorder, 104
      individuals had DSM-III-R panic disorder (the narrowly defined affected
      phenotype) and 134 had either this diagnosis or subsyndromal panic disorder
      characterized by panic attacks that failed to meet either the criterion of attack
      frequency or the number of criterion symptoms necessary for a definite diagnosis
      (the broadly defined affected phenotype). The authors conducted lod score linkage
      analyses with both phenotypes using both a dominant and a recessive model of
      inheritance for the following loci: GABRA1-GABRA5 (alpha 1-alpha 5), GABRB1 (beta
      1), GABRB3 (beta 3), and GABRG2 (gamma 2). RESULTS: The results failed to support
      the hypothesis that any of these genes cause panic disorder in a majority of the
      pedigrees. CONCLUSIONS: Within the limitations of the candidate gene linkage
      method, panic disorder does not appear to be caused by mutation in any of the
      eight GABAA receptor genes tested.

PMID- 9247396
TI  - Reported pathological childhood experiences associated with the development of
      borderline personality disorder.
AB  - OBJECTIVE: The purpose of this study was to assess a full range of pathological
      childhood experiences reported by patients with criteria-defined borderline
      personality disorder and comparison patients with other personality disorders.
      METHOD: The pathological childhood experiences reported by 467 inpatients with
      personality disorders were assessed by interviewers who used a semistructured
      research interview and were blind to clinical diagnosis. RESULTS: Of the 358
      patients with borderline personality disorder, 91% reported having been abused,
      and 92% reported having been neglected, before the age of 18. The borderline
      patients were significantly more likely than the 109 patients with other
      personality disorders to report having been emotionally and physically abused by
      a caretaker and sexually abused by a noncaretaker. They were also significantly
      more likely to report having a caretaker withdraw from them emotionally, treat
      them inconsistently, deny their thoughts and feelings, place them in the role of
      a parent, and fail to provide them with needed protection. The borderline
      patients with a childhood history of sexual abuse were significantly more likely
      than those without such a history to report having experienced all but one of the
      types of abuse and neglect studied. When all significant risk factors were
      considered together, four were found to be significant predictors of a borderline
      diagnosis: female gender, sexual abuse by a male noncaretaker, emotional denial
      by a male caretaker, and inconsistent treatment by a female caretaker.
      CONCLUSIONS: The results suggest that sexual abuse is neither necessary nor
      sufficient for the development of borderline personality disorder and that other
      childhood experiences, particularly neglect by caretakers of both genders,
      represent significant risk factors.

PMID- 9247397
TI  - Feeling unreal: 30 cases of DSM-III-R depersonalization disorder.
AB  - OBJECTIVE: In contrast to the recent surge of interest in other dissociative
      disorders, DSM-III-R depersonalization disorder has not been thoroughly
      investigated and characterized. The authors systematically elucidated its
      phenomenology, comorbidity, traumatic antecedents, and treatment history. METHOD:
      Thirty adult subjects (19 women and 11 men) were consecutively recruited and
      administered various structured and semistructured interviews as well as the self
      rated Dissociative Experiences Scale. An age- and sex-matched normal comparison
      group was also recruited. RESULTS: The mean age at onset of depersonalization
      disorder was 16.1 years (SD = 5.2). The illness had a chronic course that was
      usually continuous but sometimes episodic. Severe distress and high levels of
      interpersonal impairment were characteristic. Unipolar mood and anxiety disorders
      were common, but none emerged as specifically related to the depersonalization. A
      wide variety of personality disorders was manifested; avoidant, borderline, and
      obsessive-compulsive were most common. Although not highly traumatized, the
      subjects with depersonalization disorder reported significantly more childhood
      trauma than the normal comparison subjects. Depersonalization had been typically
      treatment refractory; only serotonin reuptake inhibitors and, to a lesser extent,
      benzodiazepines had been of any therapeutic benefit. CONCLUSIONS: This study
      supports the conceptualization of depersonalization disorder as a distinct
      disorder with a characteristic course that is independent of mood, anxiety, and
      personality symptoms. A subtle relationship may exist between childhood trauma
      and depersonalization disorder that merits further investigation. The disorder
      appears to be highly treatment refractory, and prospective treatment trials are
      warranted.

PMID- 9247398
TI  - Full and partial posttraumatic stress disorder: findings from a community survey.
AB  - OBJECTIVE: Full and partial posttraumatic stress disorder (PTSD) following trauma
      exposure were examined in a community sample in order to determine their
      prevalence and their relative importance and functional significance. METHOD: A
      standardized telephone interview with a series of trauma probes and a DSM-IV PTSD
      checklist was administered to a random sample of 1,002 persons in a midsized
      Midwestern Canadian city. The authors determined current (i.e., 1-months)
      prevalence rates of full PTSD, i.e., all DSM-IV criteria, and partial PTSD, i.e.,
      fewer than the required number of DSM-IV criterion C symptoms (avoidance/numbing)
      or criterion D symptoms (increased arousal). Additional questions about
      interference with functioning were also posed. RESULTS: The estimated prevalence
      of full PTSD was 2.7% for women and 1.2% for men. The prevalence of partial PTSD
      was 3.4% for women and 0.3% for men. Interference with work or school was
      significantly more pronounced in persons with full PTSD than in those with only
      partial symptoms, although the latter were significantly more occupationally
      impaired than traumatized persons without PTSD. CONCLUSIONS: These findings in an
      epidemiologic sample underscore observations from patient and military groups
      that many traumatized persons suffer from a subsyndromal form of PTSD. These
      persons with partial PTSD, although somewhat less impaired than persons with the
      full syndrome, nonetheless exhibit clinically meaningful levels of functional
      impairment in association with their symptoms. This subthreshold form of PTSD may
      be especially prevalent in women. Additional study of partial PTSD is warranted.

PMID- 9247399
TI  - Obsessive-compulsive disorder in the community: an epidemiologic survey with
      clinical reappraisal.
AB  - OBJECTIVE: To examine the prevalence of obsessive-compulsive symptoms and DSM-IV
      obsessive-compulsive disorder (OCD), the authors conducted a telephone survey of
      2,261 adults in four regions of Canada. METHOD: Trained lay interviewers
      administered a modified version of the OCD section of the Comprehensive
      International Diagnostic Interview. A subsample of respondents with probable
      cases and probable subclinical cases of OCD was then blindly reinterviewed by
      research personnel experienced in the assessment of OCD, using the Structured
      Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale, to
      confirm the diagnosis and gauge the severity of OCD. RESULTS: The weighted 1
      month prevalence of OCD in the entire sample according to the lay interviews was
      3.1%. Upon clinical reappraisal, the 1-month prevalence estimate of OCD dropped
      to 0.6%; an additional 0.6% had subclinical OCD. The mean Yale-Brown Obsessive
      Compulsive Scale score of the individuals with OCD was 19.0 (SD = 4.6, median =
      21); for those with subclinical OCD, the mean score was 15.4 (SD = 2.4, median =
      14). Common reasons for overdiagnosis of OCD by the lay interviewers were
      inappropriate labeling of worries or concerns as obsessions and overestimating
      the degree of interference or distress attributable to obsessive-compulsive
      symptoms. CONCLUSIONS: OCD, while hardly a rare condition, may be somewhat less
      prevalent than had been believed on the basis of previous surveys. Additional
      studies are needed to substantiate these findings and to delineate precisely the
      extent of disability and reduced quality of life attributable to OCD (and OCD
      variants) in the community.

PMID- 9247400
TI  - Eating disorders in males: a report on 135 patients.
AB  - OBJECTIVE: The goal of this study was to better understand the etiology, clinical
      characteristics, and prognosis of eating disorders in males. METHOD: All males
      with eating disorders who had been treated at Massachusetts General Hospital from
      Jan. 1, 1980, to Dec. 31, 1994, were identified. Hospital charts and psychiatric
      departmental records were reviewed to verify that the eating disorders met DSM-IV
      criteria and to abstract demographic and clinical data. RESULTS: One hundred
      thirty-five males with eating disorders were identified, of whom 62 (46%) were
      bulimic, 30 (22%) were anorexic, and 43 (32%) met criteria for an eating disorder
      not otherwise specified. There were marked differences in sexual orientation by
      diagnostic group; 42% of the male bulimic patients were identified as either
      homosexual or bisexual, and 58% of the anorexic patients were identified as
      asexual. Comorbid psychiatric disorders were common, particularly major
      depressive disorder (54% of all patients), substance abuse (37%), and personality
      disorder (26%). Many patients had a family history of affective disorder (29%) or
      alcoholism (37%). CONCLUSIONS: While most characteristics of males and females
      with eating disorders are similar, homosexuality/bisexuality appears to be a
      specific risk factor for males, especially for those who develop bulimia nervosa.
      Future research on the link between sexual orientation and eating disorders would
      help guide prevention and treatment strategies.

PMID- 9247401
TI  - Ten-year stability and predictive validity of five bulimia-related indicators.
AB  - OBJECTIVE: The authors examined the temporal stability and predictive utility of
      bulimic symptoms and related variables over the course of 10 years, from 1982 to
      1992. METHOD: The subjects were 459 women who were aged 18-22 years in 1982 and
      were surveyed in both 1982 and 1992. Each respondent completed five subscales of
      the Eating Disorders Inventory (bulimia, drive for thinness, maturity fears,
      perfectionism, and interpersonal distrust) and answered questions based on the
      DSM-III criteria for bulimia nervosa. RESULTS: The temporal stability of bulimic
      symptoms and related variables was relatively high. Bulimic status in 1982
      conferred an approximately 15-fold increase in risk 10 years later. Drive for
      thinness and, to lesser degrees, maturity fears and perfectionism received
      support as long-term predictors of bulimic symptoms. CONCLUSIONS: Bulimic
      symptoms display high temporal stability and thus may affect long-term
      functioning and well-being. Later symptoms are related to scores on specific
      subscales of the Eating Disorders Inventory administered 10 years earlier.
      Assessment and therapy should be conducted accordingly.

PMID- 9247402
TI  - Treatment for severe borderline personality disorder in 1987 and 1997.

PMID- 9247403
TI  - Images in psychiatry. Harry Stack Sullivan, 1892-1949.

PMID- 9247404
TI  - Exclusion of expansion of 50 CAG/CTG trinucleotide repeats in bipolar disorder.
AB  - OBJECTIVE: The purpose of this study was to identify the specific expanded
      CAG/CTG trinucleotide repeat associated with bipolar disorder. METHOD: The study
      employed an efficient multistage approach for using a genomic CAG/CTG screening
      set. RESULTS: The authors found no evidence of expanded repeats at 43 polymorphic
      autosomal loci and seven X chromosomal loci. Secondary screening was pursued at
      the only locus that contained a large allele (37 repeats) in the primary
      screening. No association was found between allele size and diagnostic status.
      CONCLUSIONS: It is highly unlikely that expansions in repeat size at any of the
      50 candidate trinucleotide repeat loci examined are responsible for the
      association between expanded CAG/ CTG repeats and bipolar disorder. However,
      although the authors prioritized the repeats that were a priori most likely to be
      involved, the study does not reject the more general hypothesis that expanded
      CAG/CTG repeats are implicated in the pathogenesis of bipolar disorder.

PMID- 9247405
TI  - Reduced frontal cortex inositol levels in postmortem brain of suicide victims and
      patients with bipolar disorder.
AB  - OBJECTIVE: This study aimed to evaluate aspects of second messenger function in
      the brain of suicide victims and patients with bipolar disorder. METHOD: Inositol
      and its synthetic enzyme, inositol monophosphatase, were measured in postmortem
      brain samples of 10 suicide victims, eight patients with bipolar affective
      disorder, and 10 normal comparison subjects. RESULTS: The frontal cortex inositol
      levels of the suicide victims and the patients with bipolar disorder were
      significantly less than those of the normal comparison group. No differences in
      cerebellum or occipital cortex inositol levels were found among the three groups.
      The groups also showed no differences in inositol monophosphatase activity in any
      brain area. CONCLUSIONS: These results could suggest a deficiency of second
      messenger precursor in patients with bipolar disorder and suicide victims.

PMID- 9247406
TI  - Lack of relapse with tryptophan depletion following successful treatment with
      ECT.
AB  - OBJECTIVE: Although the antidepressant mechanism of ECT is unknown, there are
      considerable data to support serotonergic involvement. The effects of tryptophan
      depletion were studied in patients with major depression treated successfully
      with ECT. METHOD: Five patients who had been successfully treated with ECT for
      major depression were studied in a randomized, double-blind, crossover design
      comparing tryptophan depletion to a placebo procedure. RESULTS: No effect of
      tryptophan depletion on mood symptoms was observed despite more than an 85%
      decrease in total serum tryptophan. CONCLUSIONS: These data suggest that
      presynaptic serotonin availability may not be necessary for the acute maintenance
      of an antidepressant response to ECT.

PMID- 9247407
TI  - Rapid tryptophan depletion in drug-free depressed patients with seasonal
      affective disorder.
AB  - OBJECTIVE: Brain serotonin systems might be involved in the pathophysiology of
      seasonal affective disorder. The authors tested whether tryptophan depletion
      alters the mood of depressed patients with seasonal affective disorder. METHOD:
      Eleven drug-free depressed patients with seasonal affective disorder underwent
      tryptophan depletion in a placebo-controlled, double-blind crossover study.
      Tryptophan depletion was induced by a 24-hour low-tryptophan diet and by
      ingestion of a tryptophan-free amino acid beverage. During control testing the
      diet and the beverage were supplemented with tryptophan. Behavioral ratings and
      plasma total and free tryptophan levels were obtained before the diet started and
      several times after administration of the beverages. RESULTS: The diet and the
      tryptophan-free amino acid drink reduced plasma total and free tryptophan levels
      by 79.0% and 87.5%, respectively. Both levels increased during control testing.
      No significant behavioral changes were induced by tryptophan depletion or control
      testing. CONCLUSIONS: The failure of tryptophan depletion to exacerbate the
      depressive syndrome suggests that dysfunctional serotonergic activity does not
      play a primary, direct role in the pathogenesis of winter depression.

PMID- 9247408
TI  - Case-control study of neuroleptic malignant syndrome.
AB  - OBJECTIVE: The authors performed a case-control study of neuroleptic malignant
      syndrome to identify potential risk factors. METHOD: Twenty-five patients with
      neuroleptic malignant syndrome were matched with 50 comparison subjects on age,
      sex, primary psychiatric diagnosis, and time of admission to the hospital. The
      records of all subjects were reviewed independently by two researchers for
      information on postulated risk factors. Exploratory direct comparisons of the two
      groups were followed by a conditional logistic regression analysis. RESULTS:
      Patients with neuroleptic malignant syndrome were more likely to be agitated or
      dehydrated before the development of neuroleptic malignant syndrome, often needed
      restraint or seclusion, and received larger doses of neuroleptics soon after
      hospitalization. Previous treatment with ECT increased vulnerability.
      CONCLUSIONS: The prevalence of neuroleptic malignant syndrome may be reduced by
      avoiding large doses of neuroleptics over short periods in the management of
      acute psychosis and by paying adequate attention to the patient's hydration and
      electrolyte status.

PMID- 9247409
TI  - Research without external funding in North American psychiatry.
AB  - OBJECTIVE: The authors investigated the extent and characteristics of published
      psychiatric research from U.S. and Canadian medical schools that was carried out
      without external funding. METHOD: They reviewed reports of unfunded research in
      14 psychiatric journals, tabulating methodological factors and topics of study.
      They surveyed first authors about their academic duties and resources used in the
      studies. RESULTS: Unfunded studies represented 26% of research reports, were
      usually prospective, most commonly dealt with phenomenology/epidemiology or
      psychopharmacology, used low levels of technology, and were accomplished on a
      modest budget of time and money. CONCLUSIONS: Unfunded studies make a substantial
      and economically efficient contribution to psychiatric research. Future
      investigations should detail the institutional conditions necessary to sustain
      this type of research productivity.

PMID- 9247410
TI  - Carnitine for valproic acid-induced hyperammonemia.

PMID- 9247411
TI  - Koro and homicidal behavior.

PMID- 9247412
TI  - Clomiphene-induced psychosis.

PMID- 9247413
TI  - Risperidone treatment of methamphetamine psychosis.

PMID- 9247414
TI  - Metronidazole-induced psychotic disorder.

PMID- 9247415
TI  - Augmentation of clozapine therapy with ondansetron.

PMID- 9247417
TI  - Light visor maintenance of light box response.

PMID- 9247416
TI  - Lamotrigine treatment of rapid cycling bipolar disorder.

PMID- 9247418
TI  - Ritual handwashing.

PMID- 9247419
TI  - Neuroleptics and bone mineral density.

PMID- 9247420
TI  - Physician-assisted suicide and abortion.

PMID- 9247421
TI  - Antidepressants and breast-feeding.

PMID- 9247422
TI  - Antidepressants and breast-feeding.

PMID- 9247423
TI  - Borderline personality and bipolar disorder.

PMID- 9247424
TI  - Borderline personality and bipolar disorder.

PMID- 9247425
TI  - ADHD and maternal smoking during pregnancy.

PMID- 9247426
TI  - On an engaging patient with paranoid schizophrenia.

PMID- 9247427
TI  - On an engaging patient with paranoid schizophrenia.

PMID- 9247428
TI  - Turkish dissociative identity disorder.

PMID- 9247429
TI  - Gloria revisited.

PMID- 9247430
TI  - Detection methods of Helicobacter pylori: accuracy and costs.
AB  - A variety of methods exist for determining gastric colonization with Helicobacter
      pylori, which has been implicated in the development of peptic ulcer disease. The
      goal of this study was to evaluate four of the current methods available in a
      clinical surgical practice setting through a prospective evaluation of 40
      consecutive patients undergoing upper diagnostic endoscopy. All patients
      underwent six antral gastric biopsies for use with the following detection
      methods: histologic demonstration of organisms (hematoxylin and eosin stain),
      direct detection of urease activity (Remel Selective Rapid Urea, Lenexa, KS), and
      culture of H. pylori. All patients also had measurement of serum immunoglobulin G
      for H. pylori by the enzyme-linked immunosorbent assay method (Corning Clinical
      Laboratories, St. Louis, MO). The infection status was established by a
      concordance of test results. The results show that H. pylori can be assessed
      equally well with histology, a rapid urease test, and serology, with all three
      tests having good sensitivity (92-100%) and specificity (85-96%). The culturing
      of the organism had poor sensitivity (42%). The benefits of the urease test are a
      much more rapid response time and a much lower cost as compared to histologic and
      serologic testing. In conclusion, the rapid urease test is the method of choice
      to detect H. pylori in those patients undergoing endoscopy in whom the
      identification of H. pylori will change their management.

PMID- 9247431
TI  - Sonographic examination of abdominal trauma by senior surgical residents.
AB  - The focused ultrasound examination is assuming an important role in the
      evaluation of abdominal trauma. We evaluated the ability of senior surgical
      residents to independently use this technique. We also evaluated the efficacy of
      a single sonographic examination instead of serial examinations. Senior surgical
      residents underwent sonography instruction by two attending surgeons certified in
      the technique. Once proficiency was attained, a single sonographic examination
      was performed on patients with abdominal trauma triaged to a Level I trauma
      center. Residents obtained additional diagnostic studies deemed appropriate.
      Ultrasound results were compared with other diagnostic studies and clinical
      course. Sonography was performed on 518 patients between January 10, 1995 and
      June 30, 1996. Mechanism of injury was blunt in 92 per cent of patients and
      penetrating in 8 per cent. There were 22 true positives, 12 false positives, 8
      false negatives, and 476 true negatives. Five of the eight false negatives were
      secondary to limited hollow viscus injuries with minimal associated
      intraperitoneal fluid. Sensitivity, specificity, accuracy, positive predictive
      value, and negative predictive value were 73.3, 97.5, 96.1, 64.7, and 98.3 per
      cent, respectively. The use of computed tomography and diagnostic peritoneal
      lavage decreased from 25 to 18 per cent and 3.2 to 0.2 per cent, respectively, as
      diagnostic tools. We conclude that surgical residents can competently perform
      trauma ultrasound. A single sonographic examination is effective and reliable.
      Sonography has essentially replaced diagnostic peritoneal lavage in our
      institution.

PMID- 9247432
TI  - Implications of fine-needle aspiration in patients with resectable pancreatic
      cancer.
AB  - A 9-year experience with fine-needle aspiration (FNA) in patients with resectable
      pancreatic adenocarcinoma was reviewed to determine whether this procedure is
      associated with positive peritoneal cytology, peritoneal recurrences, or
      decreased survival in patients who had pancreatic resection with curative intent.
      Forty-one patients underwent pancreatic resection for primary pancreatic
      adenocarcinoma from July 1987 to February 1996. Nine patients had open biopsies
      prior to definitive resection and were excluded from this study. Of the remaining
      32 patients, 21 (66%) had preoperative computed tomography-guided or
      fluoroscopically guided FNA biopsy of the pancreas for diagnosis. FNA confirmed
      the diagnosis of adenocarcinoma in 17 of 21 patients (80%). Fifteen of 21 FNA
      biopsies were performed in patients who went on to receive neoadjuvant
      chemoradiation. Twenty-eight of 32 patients (87%) had peritoneal washings at the
      time of laparotomy. Five patients had suspicious or positive washings (18%), and
      23 patients had negative washings (82%). Three of 18 patients (16.7%) who had
      both FNA and peritoneal washings and 2 of 10 patients (20%) who had no FNA but
      had peritoneal washings had positive or suspicious peritoneal cytology. Eight of
      32 patients ultimately failed in the peritoneum. Six of 21 patients (28%) who had
      prior FNA and 2 of 11 (18%) who had no prior FNA failed in the peritoneum.
      Although the number of patients is small, none of these differences proved to be
      statistically significant. No difference in median survival was observed between
      the FNA and no FNA groups. We conclude that FNA is a safe and useful tool to
      confirm the diagnosis of pancreatic cancer when patients are to be treated with
      neoadjuvant chemoradiation.

PMID- 9247433
TI  - Portal vein thrombosis in the adult: surgical implications in an era of dynamic
      imaging.
AB  - Extrahepatic portal vein thrombosis (EHPVT) is the leading cause of variceal
      hemorrhage in patients with healthy livers; however, in an era of dynamic
      imaging, the incidental discovery of EHPVT places a special burden on the surgeon
      to understand the surgical implications of the disease in this setting. During
      the period 1989 to 1995, 23 patients (12 males and 11 females) were found to have
      EHPVT. In 20 (87%), this was an unexpected finding on ultrasound (11 of 23),
      abdominal CT scan (9 of 23), or both (9 of 23). In two patients, the diagnosis
      was suspected and confirmed with angiography, whereas in the other, the lesion
      was discovered at surgery. Only seven (30%) had hemorrhage as a presenting
      complaint. More typically (61%), abdominal pain alone or pain with sepsis was the
      indication for evaluation. In 20 patients (87%), there was an identifiable
      etiology for the EHPVT. A total of 15 operations were performed on 12 patients
      (52%), in 7 (4, variceal hemorrhage, and 3, bowel ischemia) as a direct
      consequence of the EHPVT and in five, for conditions not directly related to the
      EHPVT. Three of the 23 patients (13%) died, two (17%) following surgery and one
      (9%) from advanced malignant disease. No patients with hemorrhage (seven), even
      those who required a shunt for decompression (three) or devascularization (one),
      died. We found that the diagnosis of EHPVT is usually not related to variceal
      hemorrhage, but rather, abdominal symptoms that serve as an indication for the
      imaging study. Three subsets of patients emerged: (1) those requiring no surgery
      (11 patients), (2) those requiring surgery related to hemorrhage (4 patients),
      and (3) those requiring surgery for conditions other than varices (8 patients).
      In any of these circumstances, mortality (13%) was related to the underlying
      disease process rather than EHPVT. Given the earlier recognition of EHPVT, the
      natural history of the disease has been altered, with outcome reflecting the
      underlying disease rather than the sequelae of portal hypertension.

PMID- 9247435
TI  - The "other side" of pediatric hernias: the role of laparoscopy.
AB  - The role of contralateral inguinal exploration in neonates, infants, and children
      presenting with unilateral hernias is controversial. Factors considered by
      surgeons include the patient's age, sex, and side of the clinically apparent
      hernia. The purpose of this study was to evaluate the role of diagnostic
      laparoscopy performed through the clinically apparent hernia sac to identify a
      contralateral patent processus vaginalis (CPPV) in children and limit
      contralateral exploration to CPPV-positive patients. One hundred neonates,
      infants, and children underwent laparoscopic evaluation for a CPPV through the
      ipsilateral hernia sac. There were 79 boys and 21 girls. Forty-eight of 100 (48%)
      had a CPPV identified, which was confirmed operatively. Thirty-one of 68 patients
      (46%) with a right-sided and 18 of 32 (56%) with a left-sided hernias had a CPPV
      (P = 0.39). Thirty-six of 56 (64%) patients younger than 6 months of age had a
      CPPV compared to 13 of 44 (30%) older than six months (P = 0.001). Fourteen of 21
      (67%) girls had a CPPV compared to 35 of 79 (44%) boys (P = 0.087). Laparoscopy
      through the hernia sac is a safe and effective means of identifying the presence
      of a CPPV and avoiding unnecessary contralateral inguinal exploration. Infants (<
      6 months) are much more likely to have a CPPV.

PMID- 9247434
TI  - Outcome after incision and drainage with fistulotomy for ischiorectal abscess.
AB  - Concomitant anal fistulotomy (F) and incision and drainage (I&D) of ischiorectal
      abscesses (IA) are often avoided, for fear of irreversibly impairing anal
      continence. However, failure to identify and treat the frequently associated
      trans-sphincteric anal fistula dooms the patient to recurrent anal suppurative
      disease. We have employed an aggressive approach of performing I&D and F for IA
      at the time of initial presentation. Adequate drainage is assured by placement of
      counterincisions and Penrose drains to minimize the time for healing of the
      perianal wound. Drainage is followed by a careful examination of the anal canal
      for fistula localization followed by fistulotomy, or less frequently by cutting
      seton placement. We present our experience with this approach to IA, with special
      attention paid to the evaluation of recurrence rates and anal continence. This
      paper represents a retrospective review of 80 patients with IA managed from 1983
      to 1996. Operative records and office records were reviewed, and follow-up data
      were obtained by telephone interview. Internal fistulous openings were identified
      in 55 (68.8%) patients. Surgeries included: 38 (47.5%) I&D and F, 8 (10%) I&D and
      seton, and 34 (42.5%) I&D alone. Follow-up data were available on 99 per cent of
      patients; mean, 44.3 months. Results showed a 44 per cent recurrence rate in
      those who underwent I&D as compared with 21.1 per cent following I&D and F. 11.8
      per cent of patients treated with I&D experienced a change in their level of
      continence postoperatively as compared to 15.8 per cent treated with I&D and F.
      The results indicate that an aggressive approach to IA allows identification of a
      trans-sphincteric fistula in 57.5 per cent of patients with IA. Therefore,
      optimal surgical management for IA appears to be I&D and F, resulting in a lower
      recurrence rate and comparable morbidity as compared to I&D alone.

PMID- 9247436
TI  - Nonoperative management of adult blunt splenic trauma: a 15-year experience.
AB  - From January 1989 to December 1993, 40 consecutive adult patients with ruptured
      spleen from blunt trauma were examined. Fourteen patients (35%) were taken to the
      operating room initially because of hemodynamic instability and generalized
      peritoneal signs. Twenty-six patients (65%) were hemodynamically stabilized at
      admission and treated by nonoperative management, which included strict bed rest,
      intensive care unit monitoring, frequent physical examinations, and serial
      hematocrits. Four patients failed nonsurgical management and required a
      splenectomy, three because of clinical deterioration within 1 to 3 days of
      admission; the fourth patient had recurrent bleeding 7 days after injury. The
      patients in the operative group had a greater severity of injury with a mean
      injury severity score of 26.6, four deaths, and mean transfusion requirements of
      3.7 to 4.0 units of blood, compared to a mean injury severity score of 14.6, one
      late death from cardiac causes, and average blood requirement of 0.4 to 0.7
      units. Splenic injury grading averaged 3.2 in the surgical group (grade 1, one
      patient; grade 2, four patients; grade 3, eight patients; grade 4, no patients;
      and grade 5, one patient) and differed significantly from that of the
      nonoperative group (mean = 2.4; grade 1, 12 patients; grade 2, seven patients;
      grade 3, six patients; grade 4, two patients; and grade 5, no patients). Recent
      ultrasound analysis of select grades I to IV has shown excellent resolution or
      repair of these injuries. This report extends our series from 1978 to 1993 and
      includes 144 adult patients sustaining blunt splenic ruptures. Seventy-nine (55%)
      of these patients were treated nonsurgically. Seven patients (of 80) failed
      nonoperative management and required interval laparotomy, representing a 91 per
      cent success rate. Follow-up on more than 90 per cent of the patients has shown
      no sequelae from their splenic injuries. We conclude that adult patients with
      splenic injuries from blunt trauma who are hemodynamically stable and are without
      abdominal findings requiring celiotomy can be safely managed by a nonoperative
      approach.

PMID- 9247437
TI  - Elective laparoscopic splenectomy for hematologic disorders.
AB  - Laparoscopic splenectomy has been reported to be the procedure of choice in
      selected patients with hematologic disorders. The purpose of this study is to
      review our experience with laparoscopic splenectomy in this patient population.
      The charts of all patients with hematologic disorders who presented for
      laparoscopic splenectomy over a 17-month period were reviewed. Fifteen patients,
      nine males and six females, aged 12 to 80 years (mean, 49 years) presented for
      laparoscopic splenectomy. Surgical indications included 13 cases of idiopathic
      thrombocytopenic purpura and one each of hemolytic anemia and Hodgkin's disease.
      Splenectomy was performed utilizing a four- or five-puncture laparoscopic
      technique. For completed laparoscopic splenectomies, the mean operative time was
      129 minutes, and the mean estimated blood loss was 232 cc. Mean splenic weight
      was 210 g. There were no operative deaths. There was a single intraoperative
      complication, a 1700-cc hemorrhage, and two postoperative complications:
      pneumonitis and deep venous thrombosis. Overall morbidity was 20 per cent. A
      single patient (7%) required conversion to laparotomy for completion due to
      hemorrhage. For patients completed laparoscopically, the mean hospitalization was
      1.5 days, and none required parenteral narcotics for pain control after the first
      36 hours. Laparoscopic splenectomy for patients with hematologic disorders is a
      safe and technically feasible procedure. Decreased hospitalization and discomfort
      are the primary benefits. This technique should be added to the repertoire of
      surgeons treating patients with hematologic disorders.

PMID- 9247438
TI  - Arteriovenous fistula combined with basal external penile compression: a new cure
      for male impotence.
AB  - We describe here a new procedure designed to enable reproducible sustained
      erection in a canine model. In 10 dogs, an end-to-side arteriovenous fistula was
      created between the inferior epigastric artery and deep dorsal vein. A chronic
      skin tunnel was created at the penile base. Blood flow, intracavernosal pressure
      and intraspongiosal pressure and blood gases were measured initially and 3 months
      later. Cuff application for 30 minutes was used daily. At 3 months, animals were
      sacrificed and biopsies obtained. Physiologic and histological parameters of
      erectile structures remained unchanged. Intracavernosal and intraspongiosal
      pressures increased to 33.7 +/- 6.7 mm Hg and 25.3 +/- 12.2 mm Hg (from 8.0 +/-
      2.9 and 6.0 +/- 3.6 mm Hg) after cuff application. We conclude that sustained
      erections are feasible. This procedure appears safe for human trials.

PMID- 9247440
TI  - Office-based breast ultrasonography in a small community surgical practice.
AB  - Ultrasonography is now a universally accepted ancillary modality in the diagnosis
      and management of breast diseases. The debate is whether general surgeons can
      become adept in the use of this technology in their daily practice. This is a
      report of 100 breast ultrasound procedures performed by the author in the
      confines of the surgical office. This report confirms the already known
      observation that ultrasonography complements good breast examination and
      mammography. This experience also proves that ultrasound-guided breast biopsy is
      safe, highly accurate, and cost-effective. Furthermore, this experience shows
      that ultrasound-guided interventional breast procedures can be performed safely
      by any well-trained general surgeon. This is extremely helpful in the smaller
      communities, where the general surgeon is still rightfully regarded as the expert
      in the management of breast diseases.

PMID- 9247439
TI  - Timing of coronary artery bypass grafting after acute myocardial infarction.
AB  - Appropriate timing for coronary artery bypass grafting (CABG) after acute
      myocardial infarction (AMI) remains controversial. We retrospectively examined
      423 patients who underwent CABG within 21 days of an AMI between 1992 and 1995,
      mainly for postinfarction angina and complex anatomy. The operative mortality
      rates associated with increasing time intervals between AMI and CABG were 17.4,
      9.1, 4.0, and 5.8 per cent, for less than 6 hours, 6 to 24 hours, 1 to 7 days,
      and 7 to 21 days, respectively. There were 25 (5.9%) deaths overall. Statistical
      analysis was performed to evaluate the following preoperative parameters: age,
      sex, reoperation, previous myocardial infarction (MI), MI type and location,
      anatomy, cardiogenic shock, unstable angina, ventricular arrhythmias, extending
      MI, ejection fraction, indications for surgery, cardiac index, and interval from
      infarction to CABG. Interval between operation and AMI did not have a significant
      impact on patient outcome. Factors associated with an increased hospital
      mortality were ejection fraction < 30 per cent, age > 70 years, presence of
      cardiogenic shock, and cardiac index < 1.5. Only cardiac index proved to be a
      significant predictor of mortality (P < 0.001). We conclude that the timing of
      CABG, in and of itself, has no significant effect on hospital mortality of
      symptomatic patients within 3 weeks of AMI.

PMID- 9247441
TI  - The appropriate use of the duplex scan in carotid arterial disease.
AB  - The duplex scan has become the definitive test in the diagnosis of carotid
      arterial disease. Its significance, however, has been diminished its extensive
      use for inappropriate indications. We performed a retrospective study over a four
      year period at two major hospitals to evaluate the different indications for
      carotid duplex scans. Symptoms which prompted the test, associated diseases, the
      type of physician ordering the test, and demographic data were recorded on all
      patients. Statistical analysis was used to indicate which symptoms and associated
      diseases were significant in predicting carotid disease. A total of 4,764 scans
      were reviewed. There were 4,289 studies (90%) which were negative for disease
      requiring surgery. There were a total of 12 indications for the carotid duplex
      scan in this study; the most common indications were dizziness, (20%) transient
      ischemic attack symptoms (19%) and a bruit (16%). Vascular surgeons (28%),
      Internal Medicine physicians (27%) and Family practice physicians (15%) ordered
      the duplex scan most frequently, but 39% of the positive scans were ordered by
      vascular surgeons. A history of seizures, confusion, stroke and as a preoperative
      evaluation all had a very low yield and should not be used as an indication for a
      duplex scan. However, a long smoking history, a history of known carotid disease,
      and peripheral vascular disease all had a statistical correlation with an
      abnormal duplex scan. The use of the duplex scan to rule out carotid arterial
      disease for patients with vague, uncommon symptoms is inappropriate and wasteful.

PMID- 9247442
TI  - Should ileoanal pouch surgery be denied to patients with low resting pressures?
AB  - Our aim was to evaluate any impact of preoperative resting pressure upon
      postoperative physiological results in patients undergoing ileal pouch anal
      anastomosis. Ninety patients who had undergone manometric study before and 1 year
      after surgery were divided into two groups determined by a preoperative mean
      resting pressure of > 50 mm Hg or < or = 50 mm Hg. There were significant
      differences between these two groups concerning preoperative maximum resting
      pressure (P < 0.001) and length of the high-pressure zone (P < 0.005). However,
      such a trend was not seen postoperatively. There were no differences between
      these two groups relative to postoperative mean or maximum resting pressure,
      maximum squeeze pressure, length of high-pressure zone, sensory threshold, or
      capacity. The mean resting pressure decreased after pouch surgery in 82 per cent
      of patients with a preoperative mean resting pressure of > 50 mm Hg. Conversely,
      83 per cent of patients with a preoperative mean resting pressure of < or = 50 mm
      Hg experienced an increase in mean resting pressure after pouch surgery. Only 4
      of 23 patients with a preoperative mean resting pressure of < or = 50 mm Hg had
      decreased postoperative mean resting pressure. This latter finding has not been
      previously described. However, the mean resting pressure of those four patients
      more than fully recovered within 2 to 3 years after surgery. Although
      preoperative manometry may be useful to analyze data and to counsel patients, it
      should not be used to deny patients surgery. Moreover, this study has revealed
      that patients with lower resting pressures do not suffer a deleterious decrease
      in resting pressure but actually have improved postoperative mean resting
      pressure.

PMID- 9247443
TI  - Second-look laparoscopy for visceral ischemia facilitated by preinstalled ports.
AB  - Much of the information of a second-look laparotomy can be obtained by a second
      look laparoscopy. We describe the strategy and technique of installing
      laparoscopy ports at the end of the primary laparotomy for visceral ischemia to
      facilitate a second-look laparoscopy in the ensuing 72 hours. The advantages and
      limitations are illustrated by three cases. The primary advantage appears to be
      that when second-look laparoscopy can be accomplished at a minimal cost, much of
      the inhibition to use it is removed. However, more experience is necessary before
      the procedure can be used to replace laparotomy.

PMID- 9247444
TI  - Late postoperative follow-up of patients submitted to subtotal splenectomy.
AB  - Subtotal splenectomy preserving the upper splenic pole vascularized only by the
      splenogastric vessels has been performed by us in 91 patients since 1984. This
      procedure was combined with central splenorenal shunt or portal variceal
      disconnection to treating schistosomatic portal hypertension (n = 67); it was
      combined with distal pancreatectomy to treat pancreatic cystadenoma (n = 1), and
      it was carried out for severe splenic trauma (n = 14), and to control severe
      Gaucher's disease (n = 4) and myeloid metaplasia due to myelofibrosis (n = 5).
      All patients are alive. In the present paper, we present the late postoperative
      follow up of 32 patients operated in a period that ranges from 1 to 12 years. All
      patients are satisfied with the operation. Increased counts of white blood cell
      (n = 10) and platelets (n = 7) were the only hematological alterations.
      Esophageal varices were present in 23 of 27 patients operated due to portal
      hypertension, but all of them were shorter than in the preoperative period. The
      ultrasound confirmed the presence of the splenic remnant (30 of 32) without
      significant size changes. Splenic scintigraphies were positive in 30 of 32
      patients. Subtotal splenectomy seems to be a safe procedure that can be useful in
      portal hypertension, some metabolic and hematological diseases, and benign growth
      of the distal pancreas.

PMID- 9247445
TI  - Eosinophilic colitis presenting as a left-sided colocolonic intussusception with
      secondary large bowel obstruction: an uncommon entity with a rare presentation.
AB  - Eosinophilic gastroenteritis is a quite uncommon clinical entity usually
      involving the stomach or small bowel. Occasionally, the colon is involved. We
      have encountered a case of eosinophilic colitis leading to a left-sided
      colocolonic intussusception and subsequent large bowel obstruction. This is a
      unique presentation that, to our knowledge, has not been previously reported. We
      present our case in detail as well as a review of the literature to better
      understand this rare clinical entity.

PMID- 9247446
TI  - Giant adrenal cyst: management and review of the literature.
AB  - The diagnosis of adrenal cysts is becoming increasingly more common with the
      widespread use of diagnostic imaging modalities. Most adrenal cysts are
      asymptomatic and less than 10 cm in diameter when discovered incidentally.
      Symptoms appear when adrenal cysts enlarge sufficiently to cause pain and
      gastrointestinal disturbances or become palpable. In this report, we present a
      case of a giant 45-cm right adrenal cyst manifesting as painless abdominal
      distention in a 23-year-old female. This case appears to be one of the largest
      adrenal cysts reported to date. The classification and management of adrenal
      cystic lesions is reviewed.

PMID- 9247447
TI  - Utility of a bedside Doppler in tracking left ventricular dysfunction related to
      hemorrhagic shock.
AB  - Treatment of hemorrhagic shock with fluid resuscitation alone results in
      diastolic dysfunction as measured by peak systolic pressure/end systolic volume
      ratio (PSP/ESV). The purpose of this study was to test the ability of a simple
      Doppler device to track diastolic dysfunction in hemorrhagic shock. In this
      prospective, controlled crossover study, five adult swine were resuscitated from
      hemorrhagic shock using fluids. Diastolic dysfunction was confirmed using PSP/ESV
      ratio. The effect of nitroprusside and dobutamine on this diastolic dysfunction
      was evaluated. Data (PSP/ESV, Doppler-derived acceleration, and oxygen transport
      parameters) were collected at each stage of the model. Arterial pressure and
      oxygen transport parameters corrected to baseline values; however, the PSP/ESV
      and Doppler-derived acceleration failed to correct with fluid resuscitation
      alone. Treatment with nitroprusside and dobutamine increased oxygen transport
      parameters, PSP/ESV ratio, and Doppler-derived acceleration significantly.
      Doppler-derived acceleration tracks left ventricular dysfunction seen in
      hemorrhagic shock.

PMID- 9247448
TI  - President Grover Cleveland's secret operation.

PMID- 9247449
TI  - Cognitive trauma care is undervalued: adult splenic injury as a paradigm.
AB  - Nonoperative management (NOM) of adult splenic injury is evolving. Economic
      aspects of NOM have not been examined. We hypothesize that NOM reduces hospital
      and professional charges. Surgeon, radiologist, and hospital charges and
      reimbursements, and clinical outcome were obtained for 77 consecutive adult
      splenic injury patients (> or = 15 years old) over a 3-year period. NOM succeeded
      in 30 of 31 patients. NOM was associated with lower surgeon fee ($1,148 vs
      $4,452; P < 0.0001), surgeon reimbursement ($587 vs $2,773; P = 0.0001), and
      hospital charge ($18,982 vs $48,790; P = 0.001) relative to operative management.
      Radiologist fee ($1,776 vs $2,285) and reimbursement ($1,069 vs $1,537) were not
      significantly affected. No significant difference existed between surgeon
      (primary care provider) and radiologist reimbursement for NOM. ISS poorly
      correlated with economic variables. We conclude that cost reductions are another
      potential advantage of NOM. Surgeon reimbursement for the cognitive skills
      involved in NOM is minimal. Future health finance policy should recognize the
      cognitive aspects of trauma care.

PMID- 9247450
TI  - Japan OKs organ transplants--but obstacles remain.

PMID- 9247451
TI  - Management of chronic hepatitis C: a consensus.

PMID- 9247452
TI  - Image of the month. Gastric duplication cyst.

PMID- 9247453
TI  - Appendectomy and the risk of developing ulcerative colitis or Crohn's disease:
      results of a large case-control study. South Limburg Inflammatory Bowel Disease
      Study Group.
AB  - BACKGROUND & AIMS: Appendectomy has been pointed out as a protective factor for
      ulcerative colitis (UC). The aim of this study was to elucidate the role of
      appendectomy in inflammatory bowel disease (IBD). METHODS: Prevalent as well as
      incident cases with IBD were studied separately using a pairwise age- and sex
      matched case-control study design. RESULTS: In 232 prevalent UC cases, the risk
      of developing UC was significantly lower after previous appendectomy (odds ratio
      [OR], 0.36; 95% confidence interval [CI], 0.15-0.80); subgroup analysis found a
      protective effect only in pancolitis (OR, 0.2; 95% CI, 0.02-0.7). In 208 patients
      with Crohn's disease (CD), the OR was not significantly increased but a positive
      association with appendectomy was observed in ileocecal disease. A significant
      larger proportion of appendectomies was performed close to the time of diagnosis.
      Smoking was not a confounding factor. No statistically significant associations
      were observed in incident IBD patients. Prevalent and incident patients taken
      together resulted in ORs of 0.44 (95% CI, 0.24-0.78) in UC and 1.65 (95% CI, 0.96
      2.91) in CD. CONCLUSIONS: An overall protective role of appendectomy for UC was
      observed. The observations in CD suggest that appendectomy in some cases was a
      result of still undiagnosed CD.

PMID- 9247454
TI  - Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's
      disease. Crohn's Disease Study Group.
AB  - BACKGROUND & AIMS: Interleukin 10 (IL-10) is a cytokine with immunosuppressive
      and anti-inflammatory activities. Gene-targeted IL-10-deficient mice develop a
      chronic intestinal inflammatory disease that is reminiscent of Crohn's disease.
      The present double-blind randomized multicenter trial was designed to evaluate
      the safety, tolerance, and pharmacokinetics of IL-10 in Crohn's disease. METHODS:
      Forty-six patients with active steroid-resistant Crohn's disease were treated
      with one of five doses of recombinant human IL-10 (0.5, 1, 5, 10, or 25
      micrograms/kg) or placebo administered once daily by intravenous bolus injection
      over 7 consecutive days. RESULTS: Treatment was safe and well tolerated, and no
      evidence for IL-10 accumulation was observed at the end of the treatment period.
      At the end of the study, Crohn's disease activity scores were 179 in IL-10
      treated patients and 226 in patients receiving placebo. The proportion of
      patients that experienced a complete remission at any time in the 3-week follow
      up period was 50% in the IL-10 group and 23% in placebo-treated patients.
      CONCLUSIONS: These results indicate that IL-10 administered as a daily bolus
      injection over 1 week is safe and well tolerated and may be clinically
      efficacious.

PMID- 9247455
TI  - A prospective randomized comparison between small bowel enteroclysis and small
      bowel follow-through in Crohn's disease.
AB  - BACKGROUND & AIMS: Small bowel enteroclysis (SBE) has been suggested to be
      superior to the small bowel follow-through (SBFT) for diagnosing the presence and
      extent of Crohn's disease. The aim was to perform a prospective randomized study
      at a single university medical center comparing SBE with SBFT in patients with
      Crohn's disease. METHODS: Consecutive patients with known Crohn's disease were
      randomized to receive either SBE or SBFT as the initial study and had the
      alternate study performed within 2 weeks. RESULTS: Twenty-six patients were
      enrolled. The mean time between studies was 8.7 +/- 0.8 days. Both studies were
      normal in 7 cases. The SBE was negative in 3 cases with positive findings of
      Crohn's disease by SBFT. One of these cases was a false-positive SBFT. The SBE
      and SBFT were both diagnostic of Crohn's disease in 15 cases; in 6 cases there
      was uniform agreement regarding disease pattern. The SBFT more accurately
      reported mucosal detail (n = 3) and a greater number of fistulas (n = 2). The SBE
      missed duodenal disease (n = 4). CONCLUSIONS: In known Crohn's disease, the SBFT
      is the procedure of choice. It is safer, preferred by patients, and will not miss
      gastroduodenal disease, and when the result is normal, there is no need to
      perform SBE.

PMID- 9247456
TI  - Mechanisms responsible for gastroesophageal reflux in children.
AB  - BACKGROUND & AIMS: There is limited information about the motor mechanisms
      responsible for gastroesophageal reflux (GER) in children. The aim of this study
      was to evaluate the relationship between esophageal body and lower esophageal
      sphincter (LES) motor events and the occurrence of GER. METHODS: Concurrent
      esophageal manometry and pH monitoring was conducted for 4 hours postprandially
      in 37 children referred for evaluation of suspected pathological GER. Presence of
      esophagitis and/or abnormal esophageal acid exposure was used to classify
      patients into two groups: those with pathological GER (group A; n = 24) and those
      in whom GER was not confirmed (group B; n = 13). RESULTS: GER occurred during LES
      relaxations unassociated with swallowing within 5 seconds before and 2 seconds
      after the onset of LES relaxation in 58% (group A) and 69% (group B) of the
      analyzable episodes. These swallow-independent sphincter relaxations satisfied
      criteria for classification as transient LES relaxations. An additional 23%
      (group A) and 19% (group B) of reflux episodes could have been a result of
      transient LES relaxation associated with swallowing by chance. Persistent absence
      of LES tone was an infrequent association of reflux and was confined to group A
      patients (8% of episodes). CONCLUSIONS: Transient LES relaxation is the most
      important cause of GER in children. Absent basal LES pressure is a relatively
      infrequent cause of reflux and only in children with pathological GER.

PMID- 9247457
TI  - Effect of morphine on gastroesophageal reflux and transient lower esophageal
      sphincter relaxation.
AB  - BACKGROUND & AIMS: Morphine increases residual lower esophageal sphincter (LES)
      pressure during swallow-induced LES relaxation to levels shown experimentally to
      prevent reflux. The hypothesis that morphine reduces reflux by increasing
      residual LES pressure during transient LES relaxation was tested in 8 healthy
      subjects and 8 patients with reflux disease. METHODS: Esophageal pH, LES, and
      esophageal pressures were recorded simultaneously during three sequential 30
      minute periods, basal, after morphine, and after naloxone, while the stomach was
      distended by constant infusion of 10% dextrose. RESULTS: Morphine decreased the
      number of reflux episodes and the time at pH < 4 in the patients (3.0 +/- 0.5 vs.
      6.2 +/- 1.0 [P < 0.02] and 44% +/- 7% vs. 64% +/- 7% [P < 0.05], respectively)
      but not in the healthy subjects (P = NS). Transient LES relaxation was the major
      mechanism of reflux, and although morphine did not affect residual LES pressure
      during transient LES relaxations, it decreased their number markedly in the
      patients (3.0 +/- 0.5 vs. 6.6 +/- 1.7 [P < 0.05]) and marginally in the healthy
      subjects (2.1 +/- 0.4 vs. 2.6 +/- 0.4; P = NS). Naloxone completely reversed the
      effects of morphine. CONCLUSIONS: Morphine reduces reflux in patients with reflux
      disease by decreasing the number of transient LES relaxations.

PMID- 9247458
TI  - Attention and distraction: effects on gut perception.
AB  - BACKGROUND & AIMS: Paying attention to the gut may magnify perception of
      abdominal symptoms, but the actual influence of attention by anticipatory
      knowledge and distraction on gut perception remains poorly defined. The aim of
      this study was to determine whether mental activity, attention vs. distraction,
      affects intestinal perception and whether mental effects are synergistic with
      other modulatory mechanisms. METHODS: Perception of 1-minute intestinal balloon
      distentions applied at 7-13-minute random intervals was measured in healthy
      subjects. First, distentions were tested during attention by anticipatory
      knowledge and during distraction (n = 8). Because somatic transcutaneous
      electrical nerve stimulation (TENS) reduces gut perception, distentions were then
      tested during attention alone, attention plus somatic TENS, and during
      distraction plus TENS (n = 8). RESULTS: Perception of intestinal distentions was
      higher during attention than during distraction (3.3 +/- 0.2 vs. 2.9 +/- 0.1
      [mean +/- SEM]; P < 0.05). The area of somatic projection was greater during
      attention (P < 0.05). Intestinal compliance and oral reflex relaxation remained
      unchanged. During application of somatic TENS, perception of intestinal
      distention was higher during attention than distraction (2.4 +/- 0.3 vs. 1.7 +/-
      0.2; P < 0.05). However, TENS did not alter the perception score during
      attention. CONCLUSIONS: Mental activity may modulate gut perception and overrides
      the effects of somatic TENS on gut perception.

PMID- 9247460
TI  - Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin
      in vitamin B12-deficient patients.
AB  - BACKGROUND & AIMS: Patients with previous stomach and terminal ileum resections
      are often treated with intramuscular vitamin B12 injections. Disadvantages are,
      on a worldwide scale, the frequent need for medical personnel to administer
      injections and the sometimes painful way of application. This study was designed
      to investigate the feasibility of intranasal hydroxocobalamin suppletion in
      cobalamin-deficient patients and to assess whether intranasal hydroxocobalamin
      application could be an alternative for intramuscular injection. METHODS: Six
      patients with plasma cobalamin concentrations of < 200 ng/L were recruited. A
      dose of 1500 micrograms hydroxocobalamin was applied intranasally at days 0, 14,
      and 21. Plasma cobalamin concentrations were determined 1 hour after
      hydroxocobalamin application and on days 0, 7, 21, 28, and 35. RESULTS: All
      patients showed substantial increase of cobalamin concentrations 1 hour after
      intranasal application. In these 6 patients, there was an eightfold increase of
      mean baseline cobalamin concentrations. All patients showed a sustained increase
      of baseline cobalamin concentrations 1 week after prior intranasal application of
      hydroxocobalamin. No side effects were noted. CONCLUSIONS: Intranasal application
      of hydroxocobalamin in cobalamin-deficient patients results in fast nasal
      absorption and leads to sustained increase of baseline cobalamin concentrations.

PMID- 9247459
TI  - A case-control study of dietary intake and other lifestyle risk factors for
      hyperplastic polyps.
AB  - BACKGROUND & AIMS: Despite the high prevalence of the hyperplastic polyp, little
      is known about its etiology. The aim of this study was to assess the relationship
      between diet and other lifestyle factors and the presence of colorectal
      hyperplastic polyps. METHODS: Information on diet and other known or suspected
      risk factors for colorectal cancer or adenoma was collected among 81 subjects
      with hyperplastic polyps and 480 controls. RESULTS: The multivariate-adjusted
      odds ratio (OR) for hyperplastic polyps for individuals in the upper vs. the
      lower quartile was 0.30 (95% confidence interval [CI], 0.10-0.88) for dietary
      fiber, 0.32 (95% CI, 0.11-0.96) for dietary calcium, 0.90 (95% CI, 0.27-2.95) for
      total fat, and 2.02 (95% CI, 1.05-3.91) for alcohol consumption. Compared with
      individuals in the lower category, those in the upper category of body mass index
      had a higher risk for hyperplastic polyps (OR, 4.50; 95% CI, 1.84-10.97).
      Cigarette smoking was associated with a higher risk (OR, 1.97; 95% CI, 1.02-3.81
      for > 20 pack-years vs. never), whereas an inverse association was seen for use
      of aspirin and other nonsteroidal anti-inflammatory drugs (OR, 0.29; 95% CI, 0.12
      0.67 for once per day or more vs. never). CONCLUSIONS: Hyperplastic polyps share
      common lifestyle risk factors with colorectal adenomas and carcinomas.

PMID- 9247461
TI  - Whipple's disease: staging and monitoring by cytology and polymerase chain
      reaction analysis of cerebrospinal fluid.
AB  - BACKGROUND & AIMS: Diagnostic procedures in Whipple's disease usually focus on
      the intestine, but symptomatic central nervous system involvement is a major
      threat for patients. The aim of this study was to determine the diagnostic value
      of cerebrospinal fluid (CSF) analysis. METHODS: A total of 39 CSF samples and 2
      brain biopsy specimens that were obtained from 24 patients with Whipple's disease
      at various intervals after diagnosis were examined. Five patients presented with
      neurological symptoms, 3 of them as relapses after therapy. Thirty-two CSF
      samples were examined by polymerase chain reaction for Tropheryma whippelli and
      20 CSF samples by cytology. Brain biopsy specimens were examined histologically.
      RESULTS: Positive results were obtained in 4 of 5 patients (80%) with
      neurological symptoms, in 7 of 10 patients (70%) without neurological symptoms
      examined before therapy, and in 3 of 11 patients (27%) without neurological
      symptoms studied during or after therapy. Conversion from positive to negative
      was observed in 4 patients after antibiotic treatment. CONCLUSIONS: Testing of
      CSF in Whipple's disease yields a high rate of positive results, even in patients
      without neurological symptoms. Examination of CSF is therefore potentially useful
      for initial staging and for monitoring of the efficiency of therapy.

PMID- 9247463
TI  - Gastric mucosal hydrophobicity in duodenal ulceration: role of Helicobacter
      pylori infection density and mucus lipids.
AB  - BACKGROUND & AIMS: Gastric mucosal hydrophobicity is reduced in Helicobacter
      pylori infection. Infection density is increased in duodenal ulcer (DU) compared
      with H. pylori gastritis alone, but it is unknown whether there is a
      corresponding difference in hydrophobicity or whether hydrophobicity is related
      to infection density or to mucus lipids. The aim of this study was to determine
      the relationship between H. pylori infection density and mucosal hydrophobicity,
      and between mucus lipids and hydrophobicity, and to compare results in patients
      with H. pylori-induced gastritis with and without DU. METHODS: Fifty-four
      patients, including 29 H. pylori-positive (15 with DU and 14 with gastritis
      alone) and 25 H. pylori-negative controls, were studied. Hydrophobicity was
      determined by goniometry and infection density by histology. Mucus lipids were
      determined by colorimetry and phospholipase A2 activity by radioenzymatic assay.
      RESULTS: Hydrophobicity was reduced in DU compared with gastritis alone (39
      degrees vs. 48 degrees; P < 0.05) and with healthy controls (39 degrees vs. 60
      degrees; P < 0.0001). Hydrophobicity correlated with infection density (Rs = 
      0.55; P < 0.01). Mucus triglyceride level was modestly increased with infection,
      but mucus phospholipids or lipolysis were unrelated to H. pylori and
      hydrophobicity. CONCLUSIONS: Mucosal hydrophobicity is reduced in H. pylori
      positive patients with DU compared with those having gastritic only.
      Hydrophobicity correlates with infection density but not with mucus lipid levels.

PMID- 9247462
TI  - Defects of monocyte interleukin 12 production and humoral immunity in Whipple's
      disease.
AB  - BACKGROUND & AIMS: Whipple's disease (WD) is a systemic infection in which the
      causative bacteria typically accumulate within macrophages. The aim of this study
      was to test whether this macrophage dysfunction is the cause or result of
      previously shown T-cell defects. METHODS: In vitro production of interleukin (IL)
      12, IL-10, tumor necrosis factor alpha, interferon gamma (IFN-gamma), and
      transforming growth factor beta (TGF-beta) from purified monocytes and peripheral
      blood mononuclear cells, cytokine expression on duodenal biopsy specimens, and
      serum cytokine and immunoglobulin (Ig) levels were tested in 9 patients with WD.
      RESULTS: Reduced monocyte IL-12 production and decreased IFN-gamma secretion by
      peripheral blood mononuclear cells in vitro were found, as well as reduced
      immunohistological staining for IL-12 and IFN-gamma, but no decrease in other
      cytokines in patients with WD. A similar but less severe defect in 2 relatives
      with WD argued for a genetic basis of this abnormality. Serum IgG2, an IFN-gamma
      dependent Ig subclass, and serum TGF-beta levels were reduced in patients with
      WD. CONCLUSIONS: The described monocyte defects in WD may result in a secondary
      reduction of IFN-gamma production and IgG2 serum levels. This provides a
      rationale for additive immunotherapy in patients with antibiotic-refractory WD.

PMID- 9247464
TI  - Aberrant expression of gland-type gastric mucin in the surface epithelium of
      Helicobacter pylori-infected patients.
AB  - BACKGROUND & AIMS: Helicobacter pylori is found within the gastric mucous gel
      layer and in association with the epithelial surface. The aim of this study was
      to determine the effect of H. pylori infection on mucin gene expression (MUC6,
      MUC5, and MUC1) in the gastric epithelium. METHODS: Gastric biopsy specimens were
      examined by immunohistochemistry and in situ hybridization for mucin gene
      expression. RESULTS: MUC6 was limited to mucous glands of H. pylori-negative
      patients, but 72% of H. pylori-positive patients also expressed MUC6 in surface
      mucous cells. In contrast, MUC5 mucin was found in significantly fewer surface
      mucous cells of H. pylori-positive specimens. Carbohydrates recognized by Lewis
      (Le) X and paradoxical concanavalin A (con A) staining were aberrantly expressed
      in the surface mucous cells of 16 of 27 and 17 of 23 H. pylori-positive tissues,
      respectively. Surface Le(b) was present in 26 of 27 H. pylori-positive and 19 of
      30 H. pylori-negative tissues. Eradication of H. pylori resulted in reversal of
      surface MUC5 and MUC6 expression toward normal patterns. Purified gastric mucins
      of H. pylori-positive patients bound more anti-MUC6 and anti-Le(b) than mucins
      from H. pylori-negative patients. CONCLUSIONS: The type of mucin that is normally
      limited to mucous glands is aberrantly expressed in surface mucous cells of H.
      pylori-positive patients, whereas less of the surface epithelium expresses normal
      surface-type gastric mucin.

PMID- 9247465
TI  - Effect of Helicobacter pylori products and recombinant cytokines on gastrin
      release from cultured canine G cells.
AB  - BACKGROUND & AIMS: The pathophysiology of hypergastrinemia in Helicobacter pylori
      infection is undefined, but the infected antrum shows a marked inflammatory
      response with local production of cytokines. Hypergastrinemia and inflammatory
      infiltrate clear with successful eradication. The aim of this study was to
      examine whether the cytokines tumor necrosis factor alpha or interleukin 8 (IL
      8), which are produced in the gastric mucosa of patients with H. pylori-induced
      peptic disease or H. pylori products, can stimulate gastrin release from isolated
      cultured canine G cells. METHODS: Canine G cells were isolated by collagenase
      digestion, enriched by centrifugal elutriation, incubated with cytokines,
      bacterial components, or both, and gastrin release was measured by
      radioimmunoassay. RESULTS: IL-8 (1 and 10 nmol/L) stimulated gastrin release by
      34% +/- 13% and 43% +/- 23% (P < 0.05) above basal, respectively. H. pylori
      sonicates, water extract preparations, and lipopolysaccharide had no stimulatory
      actions, but the sonicates from two of four strains potentiated the effects of IL
      8, leading to maximal gastrin release of 230% +/- 130% and 232% +/- 33% above
      basal, respectively (P < 0.05). CONCLUSIONS: IL-8 stimulated gastrin release from
      isolated G cells, and the effect was potentiated by H. pylori products. The
      interaction of cytokines and H. pylori may contribute to the hypergastrinemia
      seen in vivo.

PMID- 9247466
TI  - Differences in expression of homeobox transcription factors in proximal and
      distal human small intestine.
AB  - BACKGROUND & AIMS: Different digestive enzymes and transporters are present in
      the duodenum, jejunum, and ileum, but the factors determining region-specific
      gene expression are not yet understood. Homeobox transcription factors are
      important in defining gradients of cellular differentiation. The aim of this
      study was to investigate whether their expression differs between proximal
      (duodenal) and distal (ileal) regions of human small intestine. METHODS:
      Intestinal RNA was prepared from surgical patients, and reverse-transcription
      polymerase chain reactions (PCRs) performed with mixed sequence oligonucleotide
      primers based on conserved regions. PCR products were identified by cloning and
      sequencing. Transcript abundance was determined by Northern blotting. RESULTS:
      The human homologues were identified as Cdx-1, Cdx-2 (or Cdx-3), Pdx-1
      (previously named Islet/duodenal homeobox [Idx]-1, Ipf-1, or Stf-1), and 13 human
      homeodomain cluster genes, including HOXB3, HOXB4, and HOXA6. The relative
      abundance of some of these differed between duodenum and ileum. Pdx-1 transcripts
      were found only in duodenum, Cdx-2, Cdx-1, and HOXB3 were readily detectable in
      both regions, with Cdx-1 having a more marked distal expression. CONCLUSIONS:
      Many homeobox genes are expressed in human adult small intestinal mucosa, and
      some are found predominantly in one region.

PMID- 9247467
TI  - CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary
      tract epithelium.
AB  - BACKGROUND & AIMS: CDX1 is an intestine-specific transcription factor expressed
      early in intestinal development that may be involved in regulation of
      proliferation and differentiation of intestinal epithelial cells. We examined the
      pattern of CDX1 protein expression in metaplastic and neoplastic tissue to
      provide insight into its possible role in abnormal differentiation. METHODS:
      Tissue samples were stained by immunohistochemistry using an affinity-purified,
      polyclonal antibody against a peptide epitope of CDX1. RESULTS: Specific nuclear
      staining was found in epithelial cells of the small intestine and colon.
      Esophagus and stomach did not express CDX1 protein; however, adjacent areas of
      intestinal metaplastic tissue intensely stained for CDX1. Adenocarcinomas of the
      stomach and esophagus had both positive and negative nuclear staining for CDX1.
      Colonic epithelial cells in adenomatous polyps and adenocarcinomas had a
      decreased intensity of staining compared with normal colonic crypts in the same
      specimen. CONCLUSIONS: CDX1 may be important in the transition from normal
      gastric and esophageal epithelium to intestinal-type metaplasia. The variability
      in expression of CDX1 in gastric and esophageal adenocarcinomas suggests more
      than one pathway in the development of these carcinomas. The decrease of CDX1 in
      colonic adenocarcinomas may indicate a role for CDX1 in growth regulation and in
      the maintenance of the differentiated phenotype.

PMID- 9247469
TI  - The polarity of neurochemically defined myenteric neurons in the human colon.
AB  - BACKGROUND & AIMS: Functional classes of enteric neurons in small mammals can be
      determined by neurochemical coding and axonal projections. The aim of this study
      was to describe the projections of vasoactive intestinal peptide (VIP)-,
      tachykinin (TK)-, and calretinin-immunoreactive (IR) interneurons and circular
      muscle motor neurons in human colon. METHODS: Human colonic myenteric neurons
      were retrogradely filled with 1,1'-didodecyl 3,3,3',3'-indocarbocyanine
      perchlorate (DII) from either the myenteric plexus or the circular muscle layers
      in organotypic culture preparations. The preparations were then labeled with
      antisera, and the position and immunoreactivity of DII-filled neurons was
      recorded. RESULTS: Nine percent of circular muscle motor neurons were labeled
      with TK immunoreactivity and these projected orally; 22% were VIP-IR and
      projected anally. Fifty-one percent of myenteric neurons that projected anally to
      the myenteric ganglia were VIP-IR and none were TK-IR. In contrast, 23% of
      neurons projecting orally were TK-IR but only 2% were VIP-IR. Calretinin
      immunoreactivity was present in 23% of neurons projecting anally and 3%
      projecting orally within the myenteric plexus. Six percent of circular muscle
      motor neurons had Dogiel type II morphology, and 50% of these were TK-IR.
      CONCLUSIONS: Circular muscle motor neurons and myenteric interneurons with TK,
      VIP, and calretinin immunoreactivity in the human colon have distinct projections
      and polarity.

PMID- 9247468
TI  - Short-chain fatty acids promote the migration of colonic epithelial cells in
      vitro.
AB  - BACKGROUND & AIMS: Repair of colonic epithelial erosions requires cell migration.
      This study aimed to examine the effects of physiologically relevant short-chain
      fatty acids on migration in colonic epithelial cell lines. METHODS: Butyrate,
      propionate, and acetate were added to confluent monolayers of LIM1215 colon
      cancer cells after wounding. Migration in circular wounds was assessed after 24
      hours. RESULTS: The migration of LIM1215 cells was stimulated in a concentration
      dependent manner by all short-chain fatty acids. In four experiments, 2 mmol/L
      butyrate, 8 mmol/L propionate, and 16 mmol/L acetate induced 112.6% +/- 6.7%,
      98.5% +/- 5.4%, and 63.4% +/- 7.2% (mean +/- SEM) stimulation above control
      migration, respectively. Their effects were additive at submaximal concentrations
      and reversible. Butyrate also stimulated migration in two other colon cancer cell
      lines, Caco-2 and LIM2405. However, butyrate failed to stimulate the migration of
      nongastrointestinal and nonepithelial cell lines. The stimulatory effect of
      butyrate required protein and RNA synthesis but was independent of cell
      proliferation, presence of serum, beta-oxidation, transforming growth factor
      beta, intracellular acidification, and substratum composition. CONCLUSIONS: In
      wounded in vitro models of colonic epithelium, short-chain fatty acids promote
      cell migration. If such an effect occurs in vivo, it would have ramifications for
      the biology and pathobiology of the colonic mucosa.

PMID- 9247470
TI  - Signal transduction pathways associated with contraction during development of
      the feline gastric antrum.
AB  - BACKGROUND & AIMS: Unlike adult antral cells, feline newborn antral cells are
      unable to contract in response to agonists in the absence of extracellular
      calcium or in response to exogenous inositol 1,4,5-triphosphate (IP3) after
      permeabilization. Changes in intracellular pathways that are associated with
      these differences were examined. METHODS: In adult and kitten antrum isolated
      smooth muscle cell contraction, levels of 1,2-diacylglycerol (DAG) and IP3 were
      assessed in response to cholecystokinin (CCK). RESULTS: CCK-induced contraction
      was transient in the adult and sustained in the kitten. U73122 blocked
      contraction in adult antral cells but not kitten antral cells. In adult antral
      tissue, CCK (10(-7) mol/L) caused an early transient increase in the level of
      DAG, whereas in the newborn antrum, CCK (10(-7) mol/L) caused a sustained
      increase in the DAG level for up to 4 minutes. IP3 showed an early increase in
      both age groups. Newborn contraction is associated with an initial increase in
      IP3 and sustained elevation of DAG levels, whereas in adult antral cells, there
      is a transient increase in both IP3 and DAG. CONCLUSIONS: The relative
      inaccessibility of intracellular calcium stores in the newborn is associated with
      age-related differences in signal transduction pathways.

PMID- 9247471
TI  - Effects of calcitonin gene-related peptide on opossum esophageal smooth muscle.
AB  - BACKGROUND & AIMS: Peristaltic contraction of the esophagus and relaxation of the
      lower esophageal sphincter (LES) are mediated by nitric oxide (NO.)-producing
      myenteric nerves. NO synthase immunoreactivity and calcitonin gene-related
      peptide (CGRP) immunoreactivity colocalize in these nerves. CGRP relaxes the LES
      and decreases the amplitude of esophageal peristalsis. The aim of this study was
      to test the hypothesis that CGRP plays a role in nerve-induced responses of the
      esophagus. METHODS: Smooth muscle strips from the LES and the body of the
      esophagus were stimulated by an electrical field to evoke nerve-mediated
      responses. RESULTS: CGRP decreased the amplitude and lengthened the latency of
      the off-response, and it relaxed the LES. Tetrodotoxin did not block the CGRP
      induced LES relaxation. The CGRP antagonist CGRP 8-37 inhibited the effects of
      exogenous CGRP. It increased the amplitude and shortened the latency of the off
      response, and it increased the resting tone of the LES. CGRP 8-37 did not inhibit
      LES relaxation or esophageal contraction. N omega-nitro-L-arginine abolished
      nerve-induced relaxation of the LES muscle and the esophageal off-response but
      not the relaxation produced by CGRP. CONCLUSIONS: These data support the
      hypothesis that CGRP may decrease the LES basal tone and modulate the timing and
      amplitude of the esophageal off-responses.

PMID- 9247472
TI  - MUCLIN expression in the cystic fibrosis transmembrane conductance regulator
      knockout mouse.
AB  - BACKGROUND & AIMS: Cystic fibrosis is characterized by increased secretion of
      glycoconjugates with altered carbohydrate composition, but no specific gene
      products that show these changes have been identified. The aim of this study was
      to use a recently described sulfated mucin-like glycoprotein (MUCLIN: formerly
      called gp300) as a model glycoconjugate to study such changes in the
      gastrointestinal system in the cystic fibrosis transmembrane conductance
      regulator (CFTR) knockout mouse (cftrm1Unc). METHODS: Western and Northern blots
      were used to determine the tissue levels of MUCLIN and its messenger RNA (mRNA)
      in normal and CFTR knockout mice. Immunocytochemistry was used to determine the
      localization of MUCLIN. RESULTS: MUCLIN is expressed in the normal mouse
      intestinal tract, pancreas, and gallbladder. In CFTR knockout mice, MUCLIN shows
      increased expression at both mRNA and protein levels in pancreas and duodenum,
      but not in the gallbladder. In the duodenum, MUCLIN was localized intracellularly
      in crypt enterocytes and on the luminal surface, and luminal surface labeling was
      dramatically increased in the CFTR knockout mouse. In the CFTR knockout mouse
      duodenum and gallbladder, MUCLIN showed retarded electrophoretic migration
      indicating altered posttranslational processing. CONCLUSIONS: MUCLIN shows
      increased expression and possibly altered posttranslational processing in the
      CFTR knockout mouse and will serve as a good model for understanding changes in
      the composition of mucous secretions in patients with this disease.

PMID- 9247473
TI  - Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport
      pathway in mice.
AB  - BACKGROUND & AIMS: Duodenal bicarbonate secretion is an important factor in
      epithelial protection. The role of the cystic fibrosis transmembrane conductance
      regulator (CFTR) in acid-induced bicarbonate secretion is unknown. The aim of
      this study was to determine whether CFTR mediates acid-stimulated duodenal
      epithelial bicarbonate secretion. METHODS: Basal and stimulated bicarbonate
      secretion was examined in the cystic fibrosis murine model cftrm1UNC, which
      displays defective CFTR in various organs including chloride transport
      abnormalities in epithelia. After anesthesia, the proximal duodenum was
      cannulated and perfused with isotonic saline, and [HCO3-] was determined.
      RESULTS: Basal bicarbonate secretion was diminished in cystic fibrosis vs. normal
      mice, 2.8 +/- 0.7 vs. 4.7 +/- 1.7 mumol.cm-1.h-1, respectively (P < 0.001).
      Luminal acidification failed to elicit a bicarbonate secretory response in cystic
      fibrosis compared with normal littermates (peak response, 2.3 +/- 0.2 vs. 9.9 +/-
      1.5 mumol.cm-1.h-1, respectively; P < 0.01). Prostaglandin E2- and vasoactive
      intestinal peptide-stimulated bicarbonate secretion were also significantly
      impaired in cystic fibrosis. Defective bicarbonate secretion in cystic fibrosis
      genotypes was due to decreased net fluid secretion and [HCO3-]. CONCLUSIONS:
      Basal and stimulated proximal duodenal bicarbonate secretion may involve a CFTR
      mediated transport pathway. It is likely that CFTR, directly or indirectly, has a
      major functional role in mediating bicarbonate transport in the proximal
      duodenum.

PMID- 9247474
TI  - Role of T helper 2 cells in intestinal goblet cell hyperplasia in mice infected
      with Trichinella spiralis.
AB  - BACKGROUND & AIMS: The four principal types of intestinal epithelial cells are
      derived from multipotent stem cells. Currently, there is no information on
      factors that regulate commitment of stem cells to differentiate along one lineage
      vs. another. The aim of our study was to investigate the role of T cells in the
      regulation of small intestinal goblet cell hyperplasia in mice infected with the
      parasite Trichinella spiralis. METHODS: NIH mice were infected with T. spiralis,
      and intestinal goblet cells and cytokine response were studied. Interferon gamma
      and interleukin 5 were used as candidate T helper (Th)1 and Th2 cytokines,
      respectively. Adoptive transfer experiments were also performed. RESULTS: Small
      intestinal goblet cell hyperplasia occurred 8 days after infection with T.
      spiralis. Th1-type cells were predominant in the mesenteric lymph nodes early in
      the course of infection, with a switch to Th2-predominant cells around the time
      of goblet cell hyperplasia. Transfer of Th2-enriched mesenteric lymph node cells
      further enhanced goblet cell hyperplasia in recipient mice. Neutralization of
      interleukin 5 activity did not affect T. spiralis-induced goblet cell
      hyperplasia. CONCLUSIONS: Small intestinal goblet cell hyperplasia in T. spiralis
      infected mice is probably regulated by Th2 cells. We postulate that Th2-derived
      factors (other than interleukin 5) induce stem cells to differentiate
      preferentially along the goblet cell lineage.

PMID- 9247475
TI  - Dietary calcium inhibits the intestinal colonization and translocation of
      Salmonella in rats.
AB  - BACKGROUND & AIMS: Dietary calcium decreases the cytotoxicity of intestinal
      contents and intestinal epitheliolysis by precipitating cytotoxic surfactants
      such as bile acids. A decreased luminal cytotoxicity might not only strengthen
      the barrier function of the gut mucosa but also reinforce the protective,
      endogenous microflora. We hypothesized, therefore, that dietary calcium increases
      the resistance to intestinal infections. METHODS: Rats on a low-, medium-, or
      high-calcium purified diet were orally infected with a single dose of Salmonella
      enteritidis. The kinetics of fecal Salmonella excretion was studied to determine
      the colonization resistance. Intestinal bacterial translocation was quantitated
      by measuring urinary oxidation products of nitric oxide (NOx) excretion and
      culturing bacteria from tissues. RESULTS: Compared with the low-calcium group,
      the medium- and high-calcium diet-fed rats had a substantially improved
      colonization resistance. Calcium supplementation also reduced translocation of
      Salmonella, considering the diminished urinary NOx excretion and viable
      Salmonella counts in the Ileal Peyer's patches and spleen. Dietary calcium
      decreased the bile acid concentration and cytotoxicity of fecal water. Several
      indicators of fecal bacterial mass were significantly increased by supplemental
      calcium. CONCLUSIONS: Dietary calcium improves the colonization resistance and
      reduces the severity of gut-derived systemic infections, which is probably
      attributable to its luminal cytoprotective effects.

PMID- 9247477
TI  - Mutations in the nonstructural 5A region of hepatitis C virus and response of
      chronic hepatitis C to interferon alfa.
AB  - BACKGROUND & AIMS: Mutations in hepatitis C virus (HCV) nonstructural protein 5A
      (NS5A) may correlate with response to interferon in Japanese patients with
      chronic hepatitis C. The aim of this study was to examine whether these findings
      could be expanded to European patients infected with genotypes associated to low
      (1b) or high (3a) response rates. METHODS: Pretreatment serum samples of 66
      patients with chronic HCV infection, 48 infected with genotype 1b and 18 with 3a,
      were analyzed. RESULTS: Among patients infected with genotype 3a, 1 of 7 long
      term responders and none of 11 nonresponders showed NS5A amino acid mutations.
      Among patients infected with genotype 1b, all 7 long-term responders, but also 27
      of 41 nonresponders, showed NS5A mutations. There was no correlation between
      number of mutations and response to therapy. In 10 patients, sequences obtained
      before and after treatment were compared and failed to show any change. Serum HCV
      RNA levels did not differ between patients with and without mutations in NS5A
      sequence. CONCLUSIONS: No significant correlation was found in patients infected
      with genotypes 1b or 3a between NS5A sequence and response to interferon alfa.
      NS5A mutations do not correlate with viral load. Changes in this region were not
      found during interferon alfa treatment.

PMID- 9247476
TI  - Predictors of the efficacy of interferon therapy in chronic hepatitis C virus
      infection. Tokyo-Chiba Hepatitis Research Group.
AB  - BACKGROUND & AIMS: The relative role of virus load and hepatitis C virus (HCV)
      subtype as predictor of the efficacy of interferon (IFN) therapy is still in
      dispute. To resolve this issue, a multicenter, randomized, prospective study of
      272 patients with chronic hepatitis C but without cirrhosis was conducted.
      METHODS: The patients were randomly assigned to two different dose groups: 6
      million units (MU) or 9 MU IFN three times a week for 6 months. Serum HCV RNA
      levels and HCV subtypes were determined. RESULTS: HCV RNA negativity rate at the
      completion of treatment with 9 MU IFN was higher than that with 6 MU (75% vs.
      44%; P < 0.05). Virus eradication at 12 months after completion of treatment was
      higher in the 9 MU group than in the 6 MU group (36% vs. 25%; P < 0.05),
      especially in patients who had an intermediate virus load (10(4)-10(5) copies/mL
      by Amplicor monitor assay) (52% vs. 19%; P = 0.029). Virus eradication rate in
      patients with serotype 2 was higher than in those with serotype 1 for both
      regimens (6 MU, 53% vs. 15%; 9 MU, 76% vs. 29%; each P < 0.05). CONCLUSIONS: This
      prospective study showed that virus load, HCV serotype, and IFN dose are
      important predictors of the virological response to IFN therapy but virus load is
      the most important factor influencing the efficacy of IFN.

PMID- 9247478
TI  - GB virus C RNA in serum, liver, and peripheral blood mononuclear cells from
      patients with chronic hepatitis B, C, and D.
AB  - BACKGROUND & AIMS: No conclusive data about GB virus C (GBV-C) tropism are
      available. We have studied the presence of genomic and antigenomic GBV-C RNA in
      serum, liver, and peripheral blood cells of 56 patients with chronic hepatitis B,
      C, or D virus infection. METHODS: Genomic and antigenomic GBV-C RNA were detected
      by reverse-transcription nested polymerase chain reaction. Specificity was
      confirmed by sequencing, by chemical modification of the RNA, and by using tagged
      primers. RESULTS: Genomic GBV-C RNA was found in 10 of 56 (18%) of the sera. In
      contrast, antigenomic strand was not detected. The sequence of the amplified GBV
      C RNA from 3 patients showed a 96% homology among them and from 83% to 88% with
      previously described isolates. Genomic GBV-C RNA was found in 7 of 7 liver
      samples of the patients with serum GBV-C RNA. In 6 of these 7 patients (85%),
      antigenomic strand was found. Genomic RNA was found in 7 of 7 of the peripheral
      blood cell samples of the same 7 patients. Antigenomic GBV-C RNA was not found in
      these cells. CONCLUSIONS: These results suggest that GBV-C is a hepatotropic
      virus that replicates in the human liver. The data do not support a role for GBV
      C in chronic liver disease.

PMID- 9247479
TI  - Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic
      hemodynamics in cirrhosis.
AB  - BACKGROUND & AIMS: Therapeutic paracentesis may be associated with a circulatory
      dysfunction, manifested by a marked increase of the plasma renin activity and
      plasma norepinephrine. The aim of the study was to characterize the systemic and
      hepatic hemodynamic changes associated with paracentesis-induced circulatory
      dysfunction. METHODS: Changes in plasma renin, aldosterone, and norepinephrine,
      and in systemic and hepatic hemodynamics were assessed 1 hour and 6 days after
      complete mobilization of ascites in 37 patients treated by total paracentesis
      plus intravenous dextran-70 infusion. RESULTS: Paracentesis-induced circulatory
      dysfunction occurred in 10 patients (renin and norepinephrine increased from 9.0
      +/- 10.5 to 28.8 +/- 19.0 ng.mL-1.h-1 and from 752.0 +/- 364.0 to 1223.0 +/-
      294.0 pg/mL, respectively) and was associated with significant reduction in
      systemic vascular resistance (-13.0% +/- 2.6%; P < 0.05) and increase in hepatic
      venous pressure gradient (from 19.5 +/- 1.5 to 22.5 +/- 2.4 mm Hg; P < 0.01). In
      the remaining 27 patients, mobilization of ascites also induced a significant but
      smaller reduction in systemic vascular resistance (-5.0% +/- 1.6%; P < 0.05)
      without significant changes in renin, norepinephrine, and hepatic venous pressure
      gradient. CONCLUSIONS: Paracentesis-induced circulatory dysfunction is
      predominantly caused by an accentuation of the arteriolar vasodilation already
      present in untreated cirrhotic patients with ascites. The homeostatic activation
      of endogenous vasoactive systems may account for the increased intrahepatic
      vascular resistance associated with this condition.

PMID- 9247480
TI  - The risk of pancreatic cancer following pancreatitis: an association due to
      confounding?
AB  - BACKGROUND & AIMS: Chronic pancreatitis has been suggested as a causal risk
      factor for pancreatic cancer in a recent study. The aim of this study was to
      clarify the relationship between chronic pancreatitis and pancreatic cancer.
      METHODS: All patients in the Swedish inpatient Register with a discharge
      diagnosis of pancreatitis from 1965 to 1983 were identified. They were stratified
      into subcohorts as follows: (1) one episode of unspecified pancreatitis (n =
      823); (2) one episode of acute pancreatitis (n = 24,753); (3) recurrent
      pancreatitis (n = 7328); and (4) chronic pancreatitis (n = 4546). We also
      identified those with associated diagnoses indicating gallbladder disease or
      alcoholism. The patients were followed up through record linkage to the
      nationwide Swedish Cancer Register, Death Register, and Migration Register.
      RESULTS: After exclusion of cancers occurring in the first year, there were
      excess risks for pancreatic cancer in all subcohorts. However, the risks declined
      with time in all subcohorts. A persistent excess risk after 10 years was
      restricted to patients with associated alcohol abuse (standardized incidence
      ratio, 3.8; 95% confidence interval, 1.5-7.9). CONCLUSIONS: The findings are not
      consistent with reports that pancreatitis is causally associated with a long-term
      risk of pancreatic cancer. Selection bias, alcohol consumption, and smoking may
      contribute to some of the patterns of risk that have been observed.

PMID- 9247481
TI  - Long-term follow-up of patients with chronic pancreatitis and K-ras gene mutation
      detected in pancreatic juice.
AB  - BACKGROUND & AIMS: Conflicting reports have raised the question whether K-ras
      gene mutations in chronic pancreatitis are related to the development of
      pancreatic neoplasm. The aim of the present study was to clarify this issue by
      surveying patients with chronic pancreatitis and K-ras gene mutation over 4
      years. METHODS: K-ras point mutations at codon 12 in duodenal juices obtained
      during exocrine function tests were examined by enriched polymerase chain
      reaction-restriction fragment length polymorphism and direct DNA sequence
      analysis, and long-term follow-up of these patients was performed. RESULTS: K-ras
      gene mutation was found in 20 of 54 patients (37%) with chronic pancreatitis. The
      types of mutation were GAT in 7, GTT in 11, and TGT in 2 patients. Pancreatic
      neoplasm occurred in none of the mutation-positive patients over a mean follow-up
      period of 78 months. CONCLUSIONS: K-ras gene mutation in patients with chronic
      pencreatitis did not seem to be related to the development of pancreatic neoplasm
      during the follow-up period, and analysis of K-ras gene mutation seems of little
      use for diagnosing pancreatic neoplasm in patients with chronic pancreatitis.

PMID- 9247482
TI  - Premature oxidative aging of hepatic mitochondrial DNA in Wilson's disease.
AB  - BACKGROUND & AIMS: Aging is associated with and may be caused by acquired somatic
      mutations of the mitochondrial genome. In Wilson's disease, inherited mutations
      of a nuclear gene encoding a copper transporter cause accumulation of copper in
      the liver, particularly within mitochondria. Because copper has prooxidant
      properties and the mitochondrial genome is particularly susceptible to oxidative
      damage, we hypothesized that Wilson's disease may cause premature oxidative aging
      of mitochondrial DNA. METHODS: Hepatic DNA was screened for large mitochondrial
      DNA deletion(s) in 16 patients with Wilson's disease and 67 control subjects.
      Deleted mitochondrial DNA copies were amplified by polymerase chain reaction and
      were sequenced. RESULTS: Although 15 of the 16 patients with Wilson's disease
      were 30 years old or younger, 8 of them (50%), including the 6 patients with
      cirrhosis (100%), had diverse mitochondrial DNA deletions, whereas only 2
      controls (3%), aged 39 and 45 years, showed a mitochondrial DNA deletion.
      CONCLUSIONS: Wilson's disease is associated with frequent, diverse, and early
      deletions of mitochondrial DNA. Accumulation of prooxidant copper within hepatic
      mitochondria may cause this premature oxidative aging of mitochondrial DNA. Thus,
      inherited mutations of a nuclear gene may cause somatic mutations of the
      mitochondrial genome in this condition.

PMID- 9247483
TI  - The role of endothelial nitric oxide synthase in the pathogenesis of a rat model
      of hepatopulmonary syndrome.
AB  - BACKGROUND & AIMS: The hepatopulmonary syndrome occurs when intrapulmonary
      vasodilatation causes impaired arterial gas exchange in liver disease. The
      pathogenesis is poorly understood, although nitric oxide may be involved. Common
      bile duct ligation in the rat is a model of the hepatopulmonary syndrome, but no
      studies have evaluated NO in pulmonary vasodilatation in this model. The aim of
      this study was to determine whether NO contributes to intrapulmonary
      vasodilatation after bile duct ligation. METHODS: Endothelial and inducible NO
      synthase (NOS) levels and localization and NO activity in pulmonary artery rings
      were assessed after bile duct ligation. RESULTS: Pulmonary endothelial NOS levels
      increased and alveolar vascular staining was enhanced after bile duct ligation.
      No change in pulmonary inducible NOS levels or localization was detected.
      Increased endothelial NOS levels correlated with alterations in gas exchange and
      were accompanied by enhanced NO activity and a blunted response to phenylephrine,
      reversible by NOS inhibition, in pulmonary artery rings. Portal-vein-ligated
      animals, which do not develop intrapulmonary vasodilatation, had no changes in
      pulmonary NOS production or in NO activity in pulmonary artery rings.
      CONCLUSIONS: NO, derived from pulmonary vascular endothelial NOS, contributes to
      intrapulmonary vasodilation in animal hepatopulmonary syndrome.

PMID- 9247484
TI  - Arginine vasopressin induces contraction and stimulates growth of cultured human
      hepatic stellate cells.
AB  - BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are perisinusoidal cells
      believed to participate in the regulation of hepatic blood flow because of their
      contractile properties and presence of receptors for several vasoactive factors.
      It is unknown whether HSCs have receptors for vasopressin, one of the most potent
      endogenous vasoconstrictors. This study investigated the existence of receptors
      for and the effects of arginine vasopressin (AVP) on cultured human HSCs.
      METHODS: intracellular calcium concentration ([Ca2+]i) and cell contraction were
      measured in individual cells loaded with fura-2 using a morphometric method with
      an epifluorescence microscope coupled to a CCD imaging system (Photometrics,
      Tucson, AZ). AVP-specific binding was measured with [3H]AVP. Mitogen-activated
      protein kinase (MAPk) activity and DNA synthesis were measured by in vitro
      phosphorylation of myelin basic protein and [3H]thymidine incorporation,
      respectively. Parallel experiments were performed in vascular smooth muscle
      cells. RESULTS: AVP elicited a dose-dependent increase in [Ca2+]i and contraction
      of HSCs. Moreover, AVP increased MAPk activity, DNA synthesis, and cell number.
      These effects were similar to those observed in vascular smooth muscle cells and
      were blocked by a V1 receptor antagonist. The existence of V1 receptors was
      further confirmed by binding studies. CONCLUSIONS: Human HSCs have V1-vasopressin
      receptors that induce effects similar to those observed in vascular smooth muscle
      cells. AVP may play a role in the regulation of HSC function.

PMID- 9247485
TI  - Tumor necrosis factor alpha inhibits collagen alpha 1(I) gene expression in rat
      hepatic stellate cells through a G protein.
AB  - BACKGROUND & AIMS: Tumor necrosis factor alpha (TNF-alpha) inhibits collagen gene
      expression in cultured fibroblasts. By binding to cell surface receptors, TNF
      alpha promotes signals within the cells. The purpose of this study was to
      investigate the role played by G proteins in TNF-alpha-induced inhibition of
      collagen gene expression. METHODS: Effect of TNF-alpha on collagen alpha 1(I)
      messenger RNA (mRNA) level was measured in cultured hepatic stellate cells in
      basal condition and after inhibiting or activating G proteins or the major
      intracellular signal transduction pathways. RESULTS: TNF-alpha significantly
      decreased the level of alpha 1(I) collagen mRNA. Treatment of cells with
      pertussis toxin inhibited this effect, whereas blocking adenylate cyclase or
      protein kinase A had no effect. Likewise, blocking phospholipase A2,
      phospholipase C1 calcium channels, calmodulin, or protein kinase C did not
      eliminate the inhibitory effect of TNF-alpha on collagen mRNA. On the other hand,
      C2-ceramide and sphingomyelinase reproduced the effect of TNF-alpha on collagen
      gene expression, and TNF-alpha did not increase the effect of sphingomyelinase.
      CONCLUSIONS: TNF-alpha-induced inhibition of alpha 1(I) collagen gene expression
      in a hepatic stellate cell line may be mediated by a pertussis toxin-sensitive G
      protein. TNF-alpha may inhibit this gene by using sphingomyelin/ceramide as an
      intracellular signal transduction pathway.

PMID- 9247486
TI  - Ethanol perturbs receptor-operated cytosolic free calcium concentration signals
      in cultured rat hepatocytes.
AB  - BACKGROUND & AIMS: Studies of the acute effects of ethanol on hepatocellular free
      calcium concentration, [Ca2+]i, and on receptor-operated [Ca2+]i signals have
      produced conflicting results. The effects of ethanol on basal and receptor
      operated [Ca2+]i signals in rat hepatocytes cultured on two different
      extracellular matrices were examined. METHODS: [Ca2+]i was determined by
      digitized fluorescence microscopy and inositol 1,4,5-trisphosphate (Ins[1,4,5]P3)
      by high-performance liquid chromatography (HPLC). RESULTS: Ethanol induced an
      increase in [Ca2+]i in hepatocytes cultured on collagen I but not on the more
      physiological substratum, matrigel. Compared with hepatocytes cultured on
      matrigel, cells on collagen I exerted less responsiveness and lower amplitude of
      [Ca2+]i signals to vasopressin or phenylephrine. The effects of ethanol on
      receptor-operated [Ca2+]i signals were examined in hepatocytes cultured on
      matrigel. Incubation of hepatocytes with physiologically attainable
      concentrations of ethanol (20-30 mmol/L) for 30 minutes to 48 hours perturbed
      epidermal growth factor, phenylephrine, and lower concentration (< or = 1 nmol/L)
      of vasopressin-induced [Ca2+]i signaling by reducing the amplitude and changing
      the pattern of [Ca2+]i signals. Alcohol induced-impairment of [Ca2+]i signaling
      was associated with decreased production of Ins(1,4,5)P3. CONCLUSIONS: Alcohol
      does not itself evoke an increase in [Ca2+]i in hepatocytes cultured on matrigel
      but perturbs receptor-operated [Ca2+]i signaling. This is associated with and
      could be caused by impaired generation of Ins(1,4,5)P3.

PMID- 9247487
TI  - Myosin I is associated with zymogen granule membranes in the rat pancreatic
      acinar cell.
AB  - BACKGROUND & AIMS: The mechanisms whereby intracellular messengers mediate
      zymogen granule transport and exocytosis in the pancreatic acinar cell are not
      well defined. Electron microscopy has shown a periluminal network of actin in the
      acinar cell, suggesting a role for actin and myosin in the transport process. The
      possible involvement of two types of myosin in the secretory process was
      investigated, and their distribution in acinar cells was determined. METHODS:
      Antibodies specific to myosin I or to myosin II were used for immunocytochemistry
      and Western blot analysis. Ultrastructural studies were also performed. RESULTS:
      Western blot analysis showed that myosin I and myosin II were present in total
      pancreatic homogenate but that only myosin I was present on isolated zymogen
      granules and their membranes. By immunocytochemistry, myosin I was shown in the
      apical aspect of acinar cells colocalized with glycoprotein 2, a marker for
      zymogen granules, and actin. By immunocytochemistry, myosin I was also localized
      on isolated zymogen granules. CONCLUSIONS: The immunolocalization of myosin I to
      zymogen granule membranes and its close association with periluminal actin
      suggest that myosin I plays a direct role in the process of transport and
      exocytosis of zymogen granules in the pancreatic acinar cell.

PMID- 9247488
TI  - Gastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with
      attenuated adenomatous polyposis coli.
AB  - Gastric adenocarcinoma has been previously recognized as a potential complication
      of familial adenomatous polyposis coli (APC) and attenuated forms of APC (AAPC).
      This tumor has only been reported to originate from adenomatous polyps of the
      gastric mucosa in these clinical conditions. There have been no previous case
      reports of gastric adenocarcinoma arising from the more commonly found fundic
      gland polyps associated with AAPC or APC. We report the first definitive case of
      gastric adenocarcinoma arising from a hyperplastic polyp of the fundis of a
      patient with AAPC.

PMID- 9247489
TI  - A novel histological lesion in glucocorticoid-responsive chronic hepatitis.
AB  - In patients with chronic hepatitis, the diagnosis of autoimmune hepatitis is made
      on the basis of increased gamma-globulin levels and the presence of circulating
      autoantibodies. Because these test results are not abnormal universally in
      patients with autoimmune hepatitis, liver biopsy remains an important part of the
      evaluation. The classical histological finding in autoimmune hepatitis is
      lymphocytic infiltration of the portal triads and periportal zone (zone 1) with
      periportal hepatocyte necrosis. This case report describes 4 patients with
      glucocorticoid-responsive hepatitis, presumably autoimmune in nature, who had
      pericentral necrosis (zone 3) with relative sparing of the portal areas in their
      liver biopsy specimens, a previously undescribed histological finding in
      autoimmune hepatitis.

PMID- 9247490
TI  - The professional lives of women in gastroenterology: a Canadian comparison study
      with men.
AB  - Women are underrepresented in gastroenterology. A questionnaire examined the
      training and career experiences of female members of the Canadian Association for
      Gastroenterology (CAG) and their male counterparts. A pretested questionnaire was
      mailed to the 50 female CAG and 100 age-matched male members. Descriptive
      analyses were performed with the SAS statistical program. Questionnaires were
      returned by 38 of the women (76%) and 70 of the men (70%). All held full-time
      positions. Whereas 21.6% of the women respondents were pediatricians, all but
      2.9% of the men had adult practices. The women were more likely to never marry
      (21.1% vs. 8.6% of men), and their personal income was significantly less than
      that of men. The men reported more problems juggling their work and private life,
      whereas problems with childcare and free time were reported more often by the
      women with children. The women perceived they had greater problems than men in
      pursuing an academic career, but grant support, academic rank, and administrative
      responsibilities were actually similar for both. Gender equality of opportunity
      was found in Canadian gastroenterology through a willingness on the part of women
      to compromise. Fewer women married and had families, and they earned less money
      than the men.

PMID- 9247492
TI  - Homeodomain proteins and cell phenotype.

PMID- 9247491
TI  - The centennial year: the development of important ideas during the last 100
      years. Nutrition and the gastroenterologist: the last 100 years.

PMID- 9247493
TI  - Hepatopulmonary syndrome: is NO the right answer?

PMID- 9247494
TI  - Gender equality in gastroenterology: an achievable goal?

PMID- 9247495
TI  - Tuberculous peritonitis: can ADA keep the laparoscope away?

PMID- 9247496
TI  - Putting a brake on secretion.

PMID- 9247497
TI  - 6-MP metabolite levels: a potential guide to Crohn's disease therapy.

PMID- 9247498
TI  - Lack of efficacy of TIPS for hepatopulmonary syndrome.

PMID- 9247499
TI  - Are all these HCCs incidental? Think again!

PMID- 9247500
TI  - Systemic amyloidosis complicating inflammatory bowel disease.

PMID- 9247501
TI  - Endothelial dysfunction: does it matter? Is it reversible?
AB  - Until recently, the endothelium was regarded as a relatively inert cell layer.
      However, over the past 20 years, research has revealed an extraordinary array of
      endothelial functions, including control over coagulation, fibrinolysis, arterial
      tone and vascular growth. Importantly, endothelial dysfunction has been
      implicated as a key event in the pathogenesis of atherosclerosis, coronary
      vasoconstriction and, probably, myocardial ischemia. The recent demonstration
      that endothelial dysfunction may be reversible raises the possibility of slowing
      the progression of atherosclerosis or modifying arterial function, or both, to
      decrease the risk of acute cardiovascular events.

PMID- 9247502
TI  - Revisiting reperfusion therapy in inferior myocardial infarction.
AB  - Although thrombolytic therapy for acute myocardial infarction (MI) is recommended
      without regard for infarct location, treatment results are less impressive for
      inferior than for anterior MI because the amount of myocardium at risk is smaller
      and less strategically located, and the mortality risk is lower. Whereas the
      risks associated with anterior MI are relatively constant, high risk subsets of
      patients with an inferior MI can be identified by simple electrocardiographic
      criteria, including left precordial ST segment depression, complete
      atrioventricular heart block and right precordial ST segment elevation.
      Unfortunately, none of the placebo-controlled, randomized trials have analyzed
      the benefit of thrombolytic therapy for inferior MI in high risk versus low risk
      subsets. Thrombolytic therapy should be more successful in reducing infarct size
      and decreasing mortality in high risk patients with an inferior MI. Thrombolytic
      therapy may not decrease hospital mortality in low risk patients (baseline risk
      2% to 4%) or those with symptom duration > 6 h. Whereas it is arguable whether
      coronary angioplasty is superior to thrombolytic therapy in anterior MI, there
      are no mortality data to support using angioplasty as a primary or rescue
      reperfusion strategy instead of thrombolytic therapy in inferior MI, unless
      thrombolytic contraindications are present or the patient is in cardiogenic
      shock.

PMID- 9247503
TI  - Primary pulmonary hypertension: improved long-term effects and survival with
      continuous intravenous epoprostenol infusion.
AB  - OBJECTIVES: This study sought to determine the long-term effects of continuous
      infusion of epoprostenol (epo) therapy on survival and pulmonary artery pressure
      in patients with primary pulmonary hypertension (PPH). BACKGROUND: PPH is a
      progressive disease for which there are few effective therapies. METHODS:
      Patients with PPH and New York Heart Association functional class III or IV
      symptoms of congestive heart failure underwent right heart catheterization and
      Doppler-echocardiography to measure the maximal systolic pressure gradient
      between the right ventricle and right atrium (delta P) and cardiac output (CO).
      Doppler-echocardiography and catheterization data were compared. Patients were
      followed up long term with Doppler-echocardiography. RESULTS: Of 69 patients who
      went on to receive epo, 18 were followed up for > 330 days (range 330 to 700).
      During long-term follow-up, there was a significant reduction in delta P, which
      decreased from 84.1 +/- 24.1 to 62.7 +/- 18.2 (mean +/- SD, p < 0.01). A Kaplan
      Meier plot of survival of our study patients demonstrated improved survival
      compared with that of historical control subjects. The 1-, 2- and 3-year survival
      rates for our patients were 80% (n = 36), 76% (n = 22) and 49% (n = 6) compared
      with 10- (88%, n = 31), 20- (56%, n = 27) and 30-month (47%, n = 17) survival
      rates in historical control subjects. CONCLUSIONS: Patients receiving continuous
      infusion of epo for treatment of PPH experience a decrease in pulmonary artery
      pressure. Long-term follow-up of this single-center patient group demonstrated
      improved long-term survival during epo therapy compared with that in historical
      control subjects and confirms predicted improved outcomes based on shorter follow
      up periods.

PMID- 9247504
TI  - Hormonal therapy increases arterial compliance in postmenopausal women.
AB  - OBJECTIVES: This study investigated the effects of hormonal therapy on large
      arterial properties. BACKGROUND: Arterial stiffness is an emerging risk marker
      for coronary heart disease and is potentially modifiable. Postmenopausal use of
      hormonal therapy is associated with a lower risk of coronary heart disease.
      METHODS: Total systemic arterial compliance (SAC) and pulse wave velocity (PWV)
      were determined in 26 premenopausal and 52 postmenopausal women, 26 of whom were
      taking hormonal therapy. RESULTS: Arterial compliance was greater in the
      premenopausal group (mean +/- SEM 0.57 +/- 0.04 arbitrary compliance units [ACU])
      than in the postmenopausal group not taking hormonal therapy (0.26 +/- 0.02 ACU,
      p = 0.001). Postmenopausal women taking hormonal therapy had a significantly
      increased total SAC compared with women not taking hormonal therapy (0.43 +/-
      0.02 vs. 0.26 +/- 0.02 ACU, p = 0.001). PWV in the aortofemoral region in the
      premenopausal women was 6.0 +/- 0.2 vs. 8.9 +/- 0.3 m/s (p < 0.001) in untreated
      postmenopausal women. However, postmenopausal women taking hormonal therapy had a
      significantly lower PWV than those not taking hormonal therapy (7.9 +/- 0.2 vs.
      8.9 +/- 0.3 m/s, p = 0.01). Eleven postmenopausal women had their hormone
      replacement therapy withdrawn for 4 weeks, resulting in a significant decrease in
      SAC and a significant increase in aortofemoral PWV. CONCLUSIONS: The increased
      SAC and decreased PWV in women receiving hormonal therapy suggest that such
      therapy may decrease stiffness of the aorta and large arteries in postmenopausal
      women, with potential benefit for age-related cardiovascular disorders. The
      reduction of arterial compliance with age appears to be altered with hormonal
      therapy.

PMID- 9247505
TI  - Pathologic correlates of aortic plaques, thrombi and mobile "aortic debris"
      imaged in vivo with transesophageal echocardiography.
AB  - OBJECTIVES: This study sought to evaluate the pathologic correlates of aortic
      atheromas, thrombi and mobile "aortic debris" imaged in vivo by transesophageal
      echocardiography (TEE). BACKGROUND: Atherosclerotic plaques with various
      complexity, thrombi and debris are frequently identified by TEE during imaging of
      the aorta. However, pathologic data to characterize these lesions imaged in vivo
      are lacking. METHODS: Intraoperative TEE was performed prospectively in 31
      patients undergoing repair of aortic aneurysm or dissection. TEE was used to
      guide the surgeon to mark aortic areas of interest that were sent for pathologic
      examination. A four-point scoring system was used for both TEE and pathologic
      evaluation to grade the degree of involvement of the aortic wall with atheroma.
      Ultrasound video intensity of the aortic wall lesions was measured and compared
      with quantitative measures of wall composition at pathologic examination. The
      presence of thrombi and mobile aortic debris by TEE was noted and compared with
      pathologic findings. RESULTS: Histologic-TEE correlations were possible in 62
      aortic segments. There was 73% exact agreement between TEE and pathologic
      grading. Discrepancies were mostly in the inability of TEE to detect superficial
      ulcerations. However, separation of normal aorta and minimal intimal thickening
      (grades I and II) from more complex atheromas (grades III and IV) was observed in
      93%. For identification of thrombus, TEE had a sensitivity of 91% (29 of 32
      segments) and a specificity of 90% (27 of 30 segments). Mobile aortic debris were
      identified in six aortic segments and were confirmed at pathologic examination to
      be thrombi. Ultrasound video intensity increased with worsening complexity of
      atheroma and related significantly to aortic plaque composition at pathologic
      evaluation (r = 0.80, p < 0.0001). Ultrasound intensity of thrombi and mobile
      debris was similar and was lower than that of complex atheromas. CONCLUSIONS:
      Thus, in the evaluation of aortic pathologic segments, TEE can assess aortic
      plaque complexity and identify thrombus formation, findings that may have
      important therapeutic implications.

PMID- 9247506
TI  - Progression of the culprit lesion in unstable coronary artery disease with
      warfarin and aspirin versus aspirin alone: preliminary study.
AB  - OBJECTIVES: This study assessed whether combination therapy with aspirin and
      warfarin for 10 weeks reduces the risk of progression or reocclusion of the
      unstable coronary artery lesion. BACKGROUND: Reocclusion of the culprit coronary
      artery occurs in up to one third of patients during the 3 months after myocardial
      infarction (MI) or unstable angina and is associated with increased morbidity and
      mortality. METHODS: Fifty-seven patients presenting with unstable angina or MI
      who had an identifiable culprit lesion at coronary angiography were randomized in
      double-blind manner to receive warfarin (target international normalized ratio
      [INR] 2.0 to 2.5) or placebo in addition to aspirin (150 mg daily). Changes in
      the culprit lesion were assessed by quantitative angiography in 50 patients after
      10 weeks of therapy or after a clinical event. Progression of the culprit lesion
      was defined as a decrease in minimal lumen diameter > 0.4 mm or a new total
      occlusion. Regression was defined as an increase in minimal lumen diameter > 0.4
      mm. RESULTS: In subjects randomized to receive warfarin, the culprit lesion was
      less likely to progress (1 [4%] vs. 8 [33%]) and more likely to regress (5[19%]
      vs. 2[9%]) than in subjects receiving placebo (p = 0.02). Recurrent MI or a new
      occlusion at angiography occurred in 2 (7%) of 29 patients receiving warfarin
      versus 11 (39%) of 28 patients receiving placebo (p = 0.005). CONCLUSIONS: In
      patients with an acute coronary syndrome, combined therapy with aspirin and
      warfarin with a target INR of 2.0 to 2.5 for 10 weeks reduces the risk of
      progression or reocclusion of the culprit coronary lesion.

PMID- 9247507
TI  - Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize
      vasospastic angina without significant coronary artery narrowing.
AB  - OBJECTIVES: We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG)
      imaging to identify and localize coronary spasm and determined the most useful
      method of MIBG analysis in vasospastic angina without significant coronary
      narrowing. BACKGROUND: Various noninvasive methods have been used to detect
      vasospastic angina, but they are not very sensitive in patients with sporadic
      attacks. MIBG imaging has recently been proposed as a useful tool for detecting
      vasospastic angina. METHODS: Normal limits of both visual and quantitative
      analysis of two-dimensional polar maps (bull's-eyes) for MIBG imaging were at
      first established in 59 normal subjects. For optimal criteria of visual analysis,
      we established regional differences in abnormal MIBG defect scores. An abnormal
      region of the bull's-eye was defined as an area > 2 SD below normal. An abnormal
      regional washout rate was defined as < 0%. Using these criteria, we prospectively
      evaluated 104 patients with suspected vasospastic angina. Visual, bull's-eye and
      regional washout rate analyses were compared for overall detection of the disease
      and for individual vessel involvement. RESULTS: Overall sensitivity by these
      methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a
      significantly higher sensitivity than the other two methods. Specificity was 78%,
      72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary
      artery with washout rate analysis was 82% for the left anterior descending (LAD),
      76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The
      sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for
      bull's-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis
      showed a significantly higher sensitivity for LAD spasm than for the other two
      methods and a higher sensitivity for RCA and Cx spasms than for visual analysis.
      CONCLUSIONS: Regional washout rate analysis of MIBG imaging is a highly accurate
      technique for determining the presence and location of coronary artery spasm.

PMID- 9247508
TI  - Prediction of improvement of contractile function in patients with ischemic
      ventricular dysfunction after revascularization by fluorine-18 fluorodeoxyglucose
      single-photon emission computed tomography.
AB  - OBJECTIVES: We evaluated the use of fluorine-18 fluorodeoxyglucose (FDG) and
      single-photon emission computed tomography (SPECT) to predict improvement of left
      ventricular ejection fraction (LVEF) after revascularization. BACKGROUND: FDG
      SPECT has recently been proposed for assessment of myocardial viability. However,
      FDG SPECT still awaits validation in terms of predicting improvement of
      contractile function after revascularization in patients with poor left
      ventricular (LV) function. METHODS: Fifty-five patients with contractile
      dysfunction (including 22 with LVEF < 30%) underwent FDG SPECT during
      hyperinsulinemic glucose clamping and early thallium-201 SPECT (to assess
      perfusion). Improvement of LV function was evaluated 3 months after
      revascularization with echocardiography and radionuclide ventriculography.
      RESULTS: The 55 patients were arbitrarily classified into two groups: 19 with
      three or more viable, dysfunctional segments on FDG SPECT and 36 with less than
      three viable, dysfunctional segments. LVEF increased significantly in the first
      group, from 28 +/- 8% (mean +/- SD) before to 35 +/- 9% (p < 0.01) after
      revascularization. In the second group, LVEF remained unchanged after
      revascularization (45 +/- 14% vs. 44 +/- 14%, p = NS). The 22 patients with
      severely depressed LV function were similarly classified into two groups: 14 with
      three or more viable segments on FDG SPECT in whom LVEF improved significantly
      (25 +/- 6% vs. 32 +/- 6%) and 8 with less than three viable segments in whom LVEF
      remained unchanged (24 +/- 6% vs. 25 +/- 6%). CONCLUSIONS: This study shows that
      FDG SPECT can identify patients in whom LV function improves after
      revascularization. Because SPECT is widely available, this technique may
      contribute to more routine use of FDG for determination of viability.

PMID- 9247509
TI  - Comparison of baseline-nitrate technetium-99m sestamibi with rest-redistribution
      thallium-201 tomography in detecting viable hibernating myocardium and predicting
      postrevascularization recovery.
AB  - OBJECTIVES: This study aimed to define the optimal criteria for detecting viable
      myocardium with rest-redistribution thallium-201 (Tl-201) or baseline-nitrate
      technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography
      (SPECT) using discriminant analysis and to compare the accuracy of the two
      tracers in predicting postrevascularization recovery. BACKGROUND: Rest
      redistribution Tl-201 imaging is currently used for detection of myocardial
      viability, but the optimal variables for territory classification have not yet
      been defined. Although Tc-99m sestamibi is reportedly less effective than Tl-201,
      its reliability can be increased by injecting it during nitrate infusion.
      METHODS: In 35 patients with left ventricular (LV) dysfunction, tracer activity
      within asynergic coronary territories was quantified on rest and redistribution
      Tl-201 and baseline and nitrate Tc-99m sestamibi SPECT. Asynergic territory
      viability was evaluated on the basis of the postrevascularization functional
      outcome. RESULTS: Percent activity within asynergic territories was significantly
      influenced by their viability (p < 0.005) and the type of acquisition (p <
      0.0001) but not by the tracer used. Discriminant analysis identified
      redistribution Tl-201 activity and nitrate-induced Tc-99m sestamibi activity
      change as the two most significant predictors of postrevascularization recovery.
      The discriminant function defined for Tl-201, including redistribution activity
      and reversibility, correctly classified 38 of 56 asynergic territories, whereas
      that for Tc-99m sestamibi, including nitrate-induced activity change and activity
      in nitrate images, correctly classified 43 territories. CONCLUSIONS:
      Redistribution activity is more important than reversibility when differentiating
      viable from nonviable territories using rest-redistribution Tl-201. In Tc-99m
      sestamibi SPECT, nitrate-induced activity changes are particularly useful in
      identifying myocardial viability. Baseline-nitrate Tc-99m sestamibi SPECT appears
      no less effective than rest-redistribution Tl-201 in predicting
      postrevascularization recovery.

PMID- 9247510
TI  - Antioxidant nutrient supplementation reduces the susceptibility of low density
      lipoprotein to oxidation in patients with coronary artery disease.
AB  - OBJECTIVE: This study sought to determine the effect of antioxidant
      supplementation on the susceptibility of low density lipoprotein (LDL) to
      oxidation in patients with established cardiovascular disease (CVD). BACKGROUND:
      Data are inconsistent regarding the role of antioxidant nutrients in the
      prevention of CVD. METHODS: The study design was a 12-week, double-blind, placebo
      controlled clinical trial. Patients with CVD (n = 45) were randomized to 1)
      placebo control; 2) 400 IU of vitamin E, 500 mg of vitamin C, 12 mg of beta
      carotene (mid-dose); or 3) 800 IU of vitamin E, 1,000 mg of vitamin C, 24 mg of
      beta-carotene (high dose) daily. Reduced susceptibility of LDL to oxidation was
      estimated by an increase in lag phase (minutes). Baseline and 6- and 12-week
      measurements of lipoproteins and lag phase were obtained. Plasma levels of
      antioxidants were measured at baseline and 12 weeks. RESULTS: Concentrations of
      alpha-tocopherol, vitamin C and beta-carotene significantly increased in the mid-
      and high dose groups during the trial. Lag phase significantly increased from
      baseline (190.1 +/- 63.8 min [mean +/- SD]) to 12 weeks (391.1 +/- 153.0 min) in
      the high dose group (p < 0.01). A nonsignificant increase in lag phase in the mid
      dose group was observed during the same time interval. A dose response was found
      for mean percent change from baseline to 12 weeks for lag phase for the placebo,
      mid- and high dose groups (p = 0.004 for trend). CONCLUSIONS: A high dose
      combination of antioxidant nutrients reduces the susceptibility of LDL to
      oxidation in patients with CVD and may be useful in secondary prevention.

PMID- 9247511
TI  - Long-term anti-ischemic effects of angiotensin-converting enzyme inhibition in
      patients after myocardial infarction. The Captopril and Thrombolysis Study (CATS)
      Investigators.
AB  - OBJECTIVES: This study was conducted to test the hypothesis that angiotensin
      converting enzyme (ACE) inhibition reduces myocardial ischemia and related events
      after myocardial infarction (MI). BACKGROUND: The oxygen demand/supply ratio of
      the myocardium is influenced by angiotensin II as a result of its arterial
      vasoconstrictive and inotropic effects and through its interaction with the
      sympathetic nervous system. METHODS: We studied 244 patients who had been
      included in a double-blind, randomized, placebo-controlled, post-MI, ACE
      inhibition intervention study (Captopril and Thrombolysis Study [CATS]). All
      patients underwent exercise testing before and 3 and 12 months after hospital
      discharge. After 1-year double-blind treatment, all patients continued receiving
      single-blind placebo for 1 month. RESULTS: Total exercise time increased in both
      groups after 3 months (placebo: +86 +/- 13 s; captopril: +69 +/- 12 s, p = 0.8
      between groups) and increased further after 1 year (placebo: +13 +/- 11 s;
      captopril: +33 +/- 13 s, p = 0.7 between groups). There were also no differences
      in mean ST segment depression. During the 12 months, significantly fewer ischemia
      related events occurred in the captopril group (82 vs. 52, p = 0.015). This
      difference was found between 3 and 12 months but not during the first 3 months.
      After withdrawal from double-blind medication, nine ischemic events were reported
      in teh captopril group compared with one in the placebo group (p = 0.006 between
      groups). CONCLUSIONS: The present data show that captopril may reduce the
      incidence of ischemia-related events after MI, which becomes apparent after 3
      months. However, no anti-ischemic effect was observed during exercise testing.
      After withdrawal from ACE inhibition, a high incidence of clinical events
      occurred, suggesting a rebound phenomenon.

PMID- 9247513
TI  - Prognostic implications of exercise echocardiography in women with known or
      suspected coronary artery disease.
AB  - OBJECTIVES: The purpose of this study was to define the value of exercise
      echocardiography as an independent predictor of cardiac events in women with
      known or suspected coronary artery disease (CAD), incremental to the data
      provided by clinical evaluation and exercise testing. BACKGROUND: Exercise
      echocardiography is more accurate than exercise electrocardiography for the
      identification of CAD in women. However, the prognostic implications of exercise
      echocardiography, especially relative to exercise electrocardiography, are
      undefined. METHODS: Symptom-limited exercise echocardiography was performed in
      549 consecutive women between 1989 and 1993. Echocardiography and
      electrocardiography were performed before and after treadmill exercise; an
      abnormal result on exercise electrocardiography was defined by ST segment
      depression > 0.1 mV, ischemia by exercise echocardiography as a new or worse wall
      motion abnormality after exercise and scar by akinesia or dyskinesia at rest.
      After exclusion of six patients with uninterpretable studies (1%) and 35 (6%)
      lost to follow-up, 508 women (mean [+/-SD] age 55 +/- 11 years) were followed up
      for 41 +/- 10 months for cardiac-related death, infarction or late
      revascularization. RESULTS: The group attained 92 +/- 10% of age-predicted
      maximal heart rate, with an exercise capacity of 7 +/- 2 metabolic equivalents.
      Of 420 women with an interpretable electrocardiogram, significant ST segment
      changes were present in 68 (16%). Results of exercise echocardiography were
      normal in 413 (81%) women, positive for ischemia in 66 (13%) and scar only in 29
      (6%). No events occurred in 444 patients (89%), and 19 underwent primary
      revascularization (within 3 months of exercise test). Cardiac events occurred in
      36 women (7%), including 17 who died of cardia causes and 19 who had a myocardial
      infarction or required late revascularization for progressive symptoms. On
      univariate analysis, the variables associated with cardiac mortality and total
      cardiac events were a history of CAD, diabetes, left ventricular hypertrophy,
      exercise capacity and echocardiographic evidence of myocardial ischemia and
      infarction. A Cox proportional hazards model showed the independent predictors of
      outcome to be known CAD (odds ratio [OR] 6.6, 95% confidence interval [CI] 3.2 to
      13.7, p < 0.00001) and echocardiographic ischemia (OR 4.3, 95% CI 2.1 to 8.7, p <
      0.0001). The prognostic value of exercise echocardiography incremental to
      clinical and exercise variables was demonstrated using sequential Cox models.
      CONCLUSIONS: In this large cohort of women, exercise echocardiography provided
      key prognostic information incremental to clinical and exercise testing data.

PMID- 9247512
TI  - Atrial fibrillation in the setting of acute myocardial infarction: the GUSTO-I
      experience. Global Utilization of Streptokinase and TPA for Occluded Coronary
      Arteries.
AB  - OBJECTIVES: We examined the clinical predictors and angiographic and clinical
      outcomes associated with atrial fibrillation in the setting of acute myocardial
      infarction (MI). BACKGROUND: This condition has been studied primarily in
      prethrombolytic era small trials. METHODS: We compared baseline clinical
      characteristics, short-term clinical and angiographic outcomes and 1-year
      mortality of patients enrolled in the Global Utilization of Streptokinase and TPA
      for Occluded Coronary Arteries (GUSTO-I) trial with atrial fibrillation on
      admission electrocardiography (n = 1,026 [2.5%]) or after enrollment (n = 3,254
      [7.9%]) and those without atrial fibrillation (n = 36,611 [89.6%]). Univariable
      and multivariable analyses were used to assess relations between baseline factors
      and the development of atrial fibrillation. RESULTS: Patients with any atrial
      fibrillation more often had three-vessel coronary artery disease and initial
      Thrombolysis in Myocardial Infarction (TIMI) grade < 3 flow than those without
      the arrhythmia. In-hospital stroke was increased in patients with atrial
      fibrillation (3.1% vs. 1.3%, p = 0.0001), mainly ischemic stroke (1.8% vs. 0.5%,
      p = 0.0001). Significant multivariable predictors of later atrial fibrillation
      included advanced age, higher peak creatine kinase levels, worse Killip class and
      increased heart rate. The unadjusted mortality rate was significantly higher at
      30 days (14.3% vs. 6.2%, p = 0.0001) and at 1 year (21.5% vs. 8.6%, p < 0.0001)
      in patients with atrial fibrillation. The adjusted 30-day mortality rate remained
      significantly higher with any (odds ratio [OR] 1.3, 95% confidence interval [CI]
      1.2 to 1.4) or later (OR 1.4, 95% CI 1.3 to 1.5) atrial fibrillation but not with
      baseline atrial fibrillation (OR 1.1, 95% CI 0.88 to 1.3). CONCLUSIONS: Atrial
      fibrillation in the setting of acute MI independently predicts stroke and 30-day
      mortality. More aggressive treatment strategies in this subgroup may be warranted
      and deserve further study.

PMID- 9247514
TI  - Relevance of increased lung thallium uptake on stress imaging in patients with
      unstable angina and non-Q wave myocardial infarction: results of the Thrombolysis
      in Myocardial Infarction (TIMI)-IIIB Study.
AB  - OBJECTIVES: This study sought to determine the significance of abnormal thallium
      201 (Tl-201) lung uptake on stress imaging in the absence of perfusion
      abnormalities. BACKGROUND: Abnormal Tl-201 lung uptake, represented by an
      increased lung/heart ratio (LHR), on stress imaging is a marker of stress-induced
      left ventricular dysfunction and poor prognosis in patients with coronary artery
      disease. METHODS: We evaluate 1,271 patients from the Thrombolysis in Myocardial
      Infarction (TIMI)-IIIB trial (86% of TIMI-IIIB cohort) with unstable angina or
      non-Q wave myocardial infarction, who underwent predischarge exercise (92%) or
      dipyridamole stress (8%) Tl-201 imaging. An increased LHR (> or = 0.50) was
      related to perfusion abnormalities and adverse cardiac events at 1 year. RESULTS:
      Of 1,271 patients, there were 762 (60%) with and 509 (40%) without perfusion
      abnormalities. An increased LHR was seen in 227 patients (18%) (173 [23%] with,
      54 [11%] without perfusion abnormalities). Patients with an increased LHR had a
      lower left ventricular ejection fraction, higher body weight, lower exercise
      capacity and a higher prevalence of angina on exercise than patients with a
      normal LHR. In the two groups with increased LHR, there was no difference in age,
      hypertension, previous myocardial infarction, total exercise time, frequency of
      angina and ST segment depression on exercise. However, the group with an
      increased LHR and normal myocardial perfusion had a preponderance of women (65%
      vs. 30%, p < 0.001). At 1-year follow-up, patients with an increased LHR had a
      higher cardiac event rate than those with a normal LHR (18% vs. 10%,
      respectively, p = 0.001) despite a higher revascularization rate (28% vs. 15%, p
      < 0.001). An increased LHR was associated with increased adverse cardiac events,
      irrespective of the presence or absence of perfusion abnormalities. CONCLUSIONS:
      An increased LHR continues to be associated with higher adverse cardiac events in
      the current era of aggressive interventional management of coronary artery
      disease. An increased LHR in the absence of myocardial perfusion abnormality is
      seen mostly in women and overweight patients. However, despite the apparent
      absence of perfusion abnormalities, an increased LHR in this group is also
      associated with a higher rate of adverse cardiac events.

PMID- 9247515
TI  - Right ventricular asynergy during dobutamine-atropine echocardiography.
AB  - OBJECTIVES: We sought to analyze right ventricular contractility during
      dobutamine infusion in patients with right coronary artery disease and to
      elucidate whether the development of right ventricular asynergy aids in
      characterizing a right coronary artery stenosis. BACKGROUND: Clinical
      investigations are emphasizing the importance of right ventricular function in
      patients with coronary artery disease. Thus, prognosis of patients with inferior
      myocardial infarction is influenced by right ventricular function. This study
      describes the echocardiographic and electrocardiographic findings during
      dobutamine-atropine echocardiography in patients with right coronary artery
      disease. METHODS: We studied 31 patients with isolated right coronary artery
      disease and no previous myocardial infarction. Six patients with poor acoustic
      window were excluded (feasibility 80%). The remaining 25 patients underwent
      dobutamine-atropine echocardiography. A right coronary artery stenosis located
      before the origin of the right ventricular branches was considered proximal;
      otherwise, it was considered distal. RESULTS: Right ventricular asynergy during
      dobutamine-atropine testing developed in 17 patients (sensitivity 68%); 14 had
      proximal and 3 had distal right coronary artery disease. The following segments
      were involved: inferior (n = 17), lateral (n = 5) and outflow tract (n = 1). No
      patient showed anterior asynergy. All 17 patients had left ventricular asynergy
      as well. Ischemia-free time was 10.7 +/- 6.2 (mean +/- SD) min for the right
      ventricle and 8.9 +/- 5.2 min for the left ventricle (p < 0.05). Ischemic ST
      changes were recorded in 15 patients (in standard leads in 14 and in right
      precordial leads in 8). All patients with right precordial changes showed ST
      elevation and had right ventricular asynergy (sensitivity and specificity for
      right ventricular asynergy 47% and 100%, respectively). A control group of 25
      patients with no right coronary artery disease (5 with no disease, 15 with left
      anterior descending and 5 with left circumflex coronary artery disease) underwent
      dobutamine echocardiography. Right ventricular asynergy developed in two patients
      with left anterior descending artery stenosis (specificity 92%); in both, the
      anterior wall was affected. CONCLUSIONS: Echocardiography during dobutamine
      infusion is a reliable technique for assessing right ventricular dysfunction in
      patients with right coronary artery disease. Right ventricular contractility can
      be assessed during dobutamine echocardiography in selected patients.

PMID- 9247516
TI  - Electrocardiogram-gated intravascular ultrasound image acquisition after coronary
      stent deployment facilitates on-line three-dimensional reconstruction and
      automated lumen quantification.
AB  - OBJECTIVE: This study evaluates the feasibility, reliability and reproducibility
      of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) image
      acquisition during automated transducer withdrawal and automated three
      dimensional (3D) boundary detection for assessing on-line the result of coronary
      stenting. BACKGROUND: Systolic-diastolic image artifacts frequently limit the
      clinical applicability of such automated analysis systems. METHODS: In 30
      patients, after successful angiography-guided implantation of 34 stents in 30
      target lesions, we carried out IVUS examinations on-line with the use of ECG
      gated automated 3D analyses and conventional manual analyses of two-dimensional
      images from continuous pullbacks. These on-line measurements were compared with
      off-line 3D reanalyses. The adequacy of stent deployment was determined by using
      ultrasound criteria for stent apposition, symmetry and expansion. RESULTS: Gated
      image acquisition was successfully performed in all patients to allow on-line 3D
      analysis within 8.7 +/- 0.6 min (mean +/- SD). Measurements by on-line and off
      line 3D analyses correlated closely (r > or = 0.95), and the minimal stent lumen
      differed only minimally (8.6 +/- 2.8 mm2 vs. 8.5 +/- 2.8 mm2, p = NS). The
      conventional analysis significantly overestimated the minimal stent lumen (9.0 +/
      2.7 mm2, p < 0.005) in comparison with results of both 3D analyses. Fourteen
      stents (41%) failed to meet the criteria by both 3D analyses, all of these not
      reaching optimal expansion, but only 7 (21%) were detected by conventional
      analysis (p < 0.02). Intraobserver and interobserver comparison of stent lumen
      measurements by the automated approach revealed minimal differences (0.0 +/- 0.2
      mm2 and 0.0 +/- 0.3 mm2) and excellent correlations (r = 0.99 and 0.98,
      respectively). CONCLUSIONS: ECG-gated image acquisition after coronary stent
      deployment is feasible, permits on-line automated 3D reconstruction and analysis
      and provides reliable and reproducible measurements; these factors facilitate
      detection of the minimal lumen site.

PMID- 9247517
TI  - Maintenance of hemostasis after invasive cardiac procedures: implications for
      outpatient catheterization.
AB  - OBJECTIVES: This study investigated the efficacy of four different methods of
      arterial puncture site management during recovery from invasive cardiac
      procedures. The primary goals were less patient discomfort and improved clinical
      outcome. BACKGROUND: The increasing use of outpatient catheterization, large
      interventional devices and potent periprocedural anticoagulation regimens has
      made the reduction of groin complications a high priority. Despite these trends,
      there are no randomized trials comparing commonly used techniques in treating the
      catheter entry site for the first few hours after the procedure. METHODS: Four
      hundred consecutive patients undergoing catheterization laboratory procedures
      were randomly assigned to one of four dressing techniques applied after achieving
      hemostasis: a sandbag placed over the site; a pressure dressing constructed from
      surgical gauze and elastic tape; a commercially available compression device; and
      no use of compressive dressing. Of these 400 patients, 171 would have been
      eligible for outpatient procedures in the absence of geographic constraints. The
      dressings were removed, and ambulation was encouraged 5 h after sheath removal.
      Uniform initial compression times, patient instructions, nursing follow-up and a
      structured interview and physical examination at 24 h were used. RESULTS: The
      level of patient discomfort before and after dressing removal, as well as site
      tenderness at 24-h follow-up, was statistically similar in all four groups.
      Hematomas (typically small) and areas of ecchymosis were observed in 58 and 122
      patients, respectively, but both their frequency and size were equally
      represented in each group. Important adverse events were confined to bleeding,
      rated as mild in 5.8%, moderate in 0.8% and severe in 0.6% of patients. Again,
      all four groups were statistically similar. Comparable findings were observed in
      the subgroup of patients eligible for outpatient procedures. CONCLUSIONS: Despite
      an increase in inconvenience and expense, none of the three compression
      techniques that were investigated improved patient satisfaction or outcome.
      Therefore, the routine use of compression dressings after invasive cardiac
      procedures cannot be recommended.

PMID- 9247518
TI  - QRS changes during percutaneous transluminal coronary angioplasty and their
      possible mechanisms.
AB  - OBJECTIVES: The purpose of the study was to describe the configuration, and
      investigate the mechanisms, of QRS changes occurring during percutaneous
      transluminal coronary angioplasty (PTCA). BACKGROUND: QRS changes during PTCA
      have been attributed to both a passive ST segment shift and conduction
      disturbances (peri-ischemic block). The direct relation between ST segment shift
      and QRS changes, however, has not been established, and the definition of
      conduction disturbances remains to be clarified. METHODS: Twelve-lead
      electrocardiograms (ECGs) were recorded before PTCA, at the end of 2 min of PTCA
      and after return to baseline values in 29 patients (left anterior descending
      coronary artery [LAD] in 13 patients, right coronary artery [RCA] in 14 and left
      circumflex coronary artery in 2). Electrocardiographic complexes before and
      during PTCA were superimposed to determine the amplitudes of initial, terminal
      and total QRS deflection; the relations of QRS changes to baseline (TP segment)
      and ST segment shift; and the duration of QRS and corrected QT intervals.
      RESULTS. 1) The direction of the initial QRS deflection was unchanged, but
      changes of its amplitude occurred. 2) Terminal QRS deflection changed in all
      patients with a ST segment shift > 17% of the R amplitude, and the correlation
      between the decrease in the S amplitude and ST segment shift was significant (r =
      0.9, p < 0.01) in patients with LAD PTCA. Correlation between changes in total
      QRS amplitude and ST segment shift in patients with RCA PTCA was weaker (r =
      0.54, p = 0.056). 3) Transient conduction disturbance manifested by QRS widening
      in selected leads occurred in 2 of 29 patients. CONCLUSIONS. 1) Changes in
      terminal QRS deflection during PTCA are proportional to the magnitude of the ST
      segment shift. 2) Conduction disturbances manifested by increased QRS duration
      occurred infrequently. We suggest that the term peri-ischemic block be applied
      only to changes in QRS configuration associated with QRS widening.

PMID- 9247519
TI  - Utility of preload alteration in assessment of left ventricular filling pressure
      by Doppler echocardiography: a simultaneous catheterization and Doppler
      echocardiographic study.
AB  - OBJECTIVES: The aim of this study was to demonstrate the usefulness of preload
      alterations in assessing left ventricular filling pressures with transmitral
      Doppler velocity curves. BACKGROUND: Doppler mitral inflow velocities, used to
      estimate left ventricular filling pressures noninvasively, are limited in
      predicting left ventricular filling pressures, especially in patients with normal
      systolic function and a "pseudonormal" mitral filling pattern. METHODS: Forty
      nine patients were studied in the cardiac catheterization laboratory with
      simultaneous Doppler echocardiography using high fidelity catheters to compare
      left ventricular diastolic filling pressures (pre-A wave left ventricular
      pressure) and Doppler mitral inflow at baseline and during reduction of preload
      during the strain phase of the Valsalva maneuver (n = 27) or sublingual
      nitroglycerin (n = 36), or both (n = 14). Doppler measurements consisted of E
      (initial peak velocity), A (velocity at atrial contraction), deceleration time
      (time from E velocity to deceleration of flow extrapolated to baseline) and
      absolute A wave velocity (A' [peak A wave velocity minus velocity at onset of
      atrial contraction]). RESULTS: In patients with high pre-A wave pressure (> or 15
      mm Hg), there was a greater change in the E/A' ratio during the Valsalva maneuver
      than in patients with a normal pre-A wave pressure (-1.22 +/- 1.1 vs. -0.35 +/-
      0.17; p = 0.02). A similar change was seen when comparing the change in the E/A'
      ratio after administration of nitroglycerin in patients with a high versus a
      normal pre-A wave pressure (0.81 +/- 0.49 vs. 0.18 +/- 0.17; p < 0.001). These
      differences were present in patients with a normal E/A ratio at baseline.
      CONCLUSIONS: Alterations in preload during assessment of Doppler
      echocardiographic indexes may be useful in noninvasively assessing left
      ventricular filling pressures.

PMID- 9247520
TI  - Transient right but not left ventricular dysfunction after strenuous exercise at
      high altitude.
AB  - OBJECTIVES: We sought to evaluate whether prolonged exercise in ultramarathon
      runners results in left ventricular (LV) damage. BACKGROUND: Strenuous exercise
      has been reported to cause LV damage. METHODS: Fourteen runners who completed an
      ultramarathon at high altitude underwent echocardiography, finger-tip oximetry
      and blood measurements of cardiac troponin I (cTnI) and creatine kinase, MB
      fraction (CK-MB) levels before, immediately after and 1 day after the race.
      RESULTS: At baseline, the echocardiograms showed normal LV and right ventricular
      (RV) size and function in all subjects, as well as mild tricuspid regurgitation
      in nine subjects, with normal estimated pulmonary artery systolic pressure (mean
      28 mm Hg). At baseline, all oxymetric readings and CK-MB measurements were
      normal, and cTnI was undetectable. Immediately after the race, the
      echocardiograms showed the expected augmentation of global and segmental LV
      function in all subjects. Although the RV was normal in nine subjects, five
      developed marked RV dilation and hypokinesia, paradoxic septal motion, pulmonary
      hypertension and wheezing. CK-MB values were elevated in all subjects. In all but
      one subject cTnI was undetectable. In that subject there was a small elevation in
      cTnI accompanied by severe RV dysfunction and pulmonary hypertension. At the 1
      day follow-up study, the echocardiographic measurements had normalized in all
      subjects. CONCLUSIONS: In trained athletes, strenuous exercise at high altitude
      did not result in LV damage. However, wheezing, reversible pulmonary hypertension
      and RV dysfunction occurred in a third of those completing the race. The
      incidence and pathogenesis of these findings remain to be determined.

PMID- 9247521
TI  - Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation
      of left ventricular diastolic function.
AB  - OBJECTIVES: This study assessed the clinical utility of mitral annulus velocity
      in the evaluation of left ventricular diastolic function. BACKGROUND: Mitral
      inflow velocity recorded by Doppler echocardiography has been widely used to
      evaluate left ventricular diastolic function but is affected by other factors.
      The mitral annulus velocity profile during diastole may provide additional
      information about left ventricular diastolic function. METHODS: Mitral annulus
      velocity during diastole was measured by Doppler tissue imaging (DTI) 1) in 59
      normal volunteers (group 1); 2) in 20 patients with a relaxation abnormality as
      assessed by Doppler mitral inflow variables (group 2) at baseline and after
      saline loading; 3) in 11 patients (group 3) with normal diastolic function before
      and after intravenous nitroglycerin infusion; and 4) in 38 consecutive patients
      (group 4) undergoing cardiac catheterization in whom mitral inflow velocity and
      tau as well as mitral annulus velocity were measured simultaneously. RESULTS: In
      group 1, mean +/- SD peak early and late diastolic mitral annulus velocity was
      10.0 +/- 1.3 and 9.5 +/- 1.5 cm/s, respectively. In group 2, mitral inflow
      velocity profile changed toward the pseudonormalization pattern with saline
      loading (deceleration time 311 +/- 84 ms before to 216 +/- 40 ms after
      intervention, p < 0.001), whereas peak early diastolic mitral annulus velocity
      did not change significantly (5.3 +/- 1.2 cm/s to 5.7 +/- 1.4 cm/s, p = NS). In
      group 3, despite a significant change in mitral inflow velocity profile after
      nitroglycerin, peak early diastolic mitral annulus velocity did not change
      significantly (9.5 +/- 2.2 cm/s to 9.2 +/- 1.7 cm/s, p = NS). In group 4, peak
      early diastolic mitral annulus velocity (r = -0.56, p < 0.01) and the early/late
      ratio (r = -0.46, p < 0.01) correlated with tau. When the combination of normal
      mitral inflow variables with prolonged tau (> or = 50 ms) was classified as
      pseudonormalization, peak early diastolic mitral annulus velocity < 8.5 cm/s and
      the early/late ratio < 1 could identify the pseudonormalization with a
      sensitivity of 88% and specificity of 67%. CONCLUSIONS: Mitral annulus velocity
      determined by DTI is a relatively preload-independent variable in evaluating
      diastolic function.

PMID- 9247522
TI  - Clinical variables affecting recovery of left atrial mechanical function after
      cardioversion from atrial fibrillation.
AB  - OBJECTIVES: We sought to evaluate the effect of clinical factors on recovery of
      atrial function after cardioversion for atrial fibrillation. BACKGROUND: Lack of
      effective mechanical atrial function (EMAF) after cardioversion of atrial
      fibrillation predisposes to thromboembolic complications and delays improvement
      in functional capacity. METHODS: Fifty-two patients underwent cardioversion
      (group I, electrical cardioversion, n = 40; group II, pharmacologic or
      spontaneous cardioversion, n = 12) for atrial fibrillation. Serial transmitral
      inflow Doppler variables were recorded after cardioversion until EMAF (atrial
      filling velocity > 0.50 m/s) was seen. Clinical variables (age, duration of
      atrial fibrillation, left ventricular ejection fraction, left atrial diameter,
      underlying cardiovascular disease, antiarrhythmic drug therapy and mode of
      cardioversion) were tested for an association with the outcomes of recovery of
      atrial function by day 3 and day 7. RESULTS: Effective mechanical atrial function
      recovered in 68% of patients by day 3 and in 76% by day 7 after cardioversion.
      The mode of cardioversion was significantly associated with recovery of atrial
      function by day 3 in bivariate and multivariate analyses (odds ratio 0.12, 95%
      confidence interval 0.01 to 1.0, for electrical cardioversion). None of the
      variables had an association with recovery of atrial function by day 7. Group I
      patients took a longer time to recover atrial function than group II patients (p
      = 0.012). In addition, group I patients had a significantly lower peak atrial
      filling velocity (mean [+/-SD] 0.39 +/- 0.19 m/s vs. 0.56 +/- 0.16 m/s) and a
      higher early filling to atrial filling velocity ratio (2.5 +/- 1.2 vs. 1.5 +/-
      0.5) after cardioversion. CONCLUSIONS: A high proportion of patients recover EMAF
      within 1 week after cardioversion. Patients who undergo electrical cardioversion
      display a greater degree and a longer duration of mechanical atrial dysfunction
      than those who convert pharmacologically or spontaneously.

PMID- 9247523
TI  - Efficacy and safety of d,l-sotalol in patients with ventricular tachycardia and
      in survivors of cardiac arrest.
AB  - OBJECTIVE: The aim of this study was to assess the antiarrhythmic efficacy and
      safety of d,l-sotalol in patients with ventricular tachycardia (VT) or
      ventricular fibrillation (VF) and in survivors of cardiac arrest and to identify
      the factors that are associated with arrhythmia suppression and therefore might
      be helpful in predicting drug efficacy. BACKGROUND: Despite increasing use of the
      class III antiarrhythmic agent d,l-sotalol, data on its short- and long-term
      efficacy in a large patient cohort are lacking. Information on its long-term
      tolerability and safety is limited. METHODS: A total of 396 patients with
      inducible sustained VT or VF (VT/VF) underwent programmed stimulation before and
      after receiving oral d,l-sotalol (240 to 640 mg/day). Patients in whom VT/VF was
      rendered either noninducible or more difficult to induce (more extrastimuli or
      faster drive cycle length needed for VT/VF induction) were discharged on a
      regimen of oral d,l-sotalol. RESULTS: d,l-Sotalol suppressed VT/VF in 151
      patients (38.1%) and rendered the arrhythmia more difficult to induce in 76
      patients (19.2%). The extent of drug-induced prolongation of right ventricular
      refractoriness and a shorter VT cycle length at baseline were independent
      predictors of immediate drug efficacy. Torsade de pointes developed in seven
      patients (1.8%). Two hundred ten patients (53%) continued to receive d,l-sotalol
      and were followed up for 34 +/- 18 months (mean +/- SD). The actuarial rates for
      the absence of arrhythmic recurrence (either VT/VF or sudden death) at 1 and 3
      years were 89% and 77%, respectively. Actuarial rates for overall survival at 1
      and 3 years were 94% and 86%, respectively. VT/VF suppression by d,l-sotalol was
      an independent discriminant variable that separated patients with and without
      arrhythmia recurrence. However, noninducibility of VT/VF did not predict freedom
      from sudden death. CONCLUSION: Oral d,l-sotalol is effective and safe in patients
      with VT/VF. However, sudden cardiac death develops in a significant proportion of
      patients, and programmed stimulation seems to be of limited value for its
      prediction.

PMID- 9247524
TI  - Is mode switching beneficial? A randomized study in patients with paroxysmal
      atrial tachyarrhythmias.
AB  - OBJECTIVES: We sought 1) to compare three pacing modalities-DDDR with mode
      switching (DM), DDDR with conventional upper rate behavior (DR) and VVIR (VR)-in
      patients with a history of atrial tachyarrhythmias, and 2) to assess the efficacy
      of six mode-switching algorithms. BACKGROUND: A history of atrial
      tachyarrhythmias has been a relative contraindication to dual-chamber pacing.
      Several mode-switching algorithms have recently been developed to prevent rapid
      tracking of atrial tachyarrhythmias. METHODS: Forty-eight patients (mean age 64
      years, 58% male) with a history of atrial tachyarrhythmias and heart block had a
      DM pacemaker implanted. Pacemakers were programmed to DM, DR and VR modes for 4
      weeks each in a randomized crossover design. All subjects used a patient
      activated electrocardiographic (ECG) recorder throughout the study and
      additionally underwent ambulatory ECG monitoring and a treadmill exercise test in
      each mode. They completed three symptom questionnaires at the end of each pacing
      period. At the end of the study, patients chose their preferred pacing period.
      RESULTS: DM was significantly better than VR mode objectively (exercise time DM
      8.1 min, VR 7.0 min, p < 0.01) and subjectively (perceived well-being DM 69, VR
      51, p < 0.001; functional class DM 2.2, VR 2.5, p < 0.05; subjective symptom
      score DM 21.2, VR 26.8, p = 0.01). Patient-perceived well-being was significantly
      better with DM than with DR mode (DM 69, DR 60, p = 0.02). DM mode was the
      preferred pacing period (DM 51%, DR 14%, VR 14%). Early termination of pacing
      because of adverse symptoms was requested by 33% of patients during VR, 19%
      during DR but only 3% during DM mode. A higher proportion of patients with a fast
      mode-switching device preferred DM mode (fast 55%, slow 49%), whereas no patients
      with a fast mode-switching device chose VR as the preferred mode (fast 0%, slow
      19%). In the subgroup of patients who had had atrioventricular node ablation, DM
      was also preferred to VR mode (DM 53%, VR 27%). Overall, there were only two
      cases of inappropriate mode switching and one case of inappropriate tracking of
      an atrial tachyarrhythmia. CONCLUSIONS: DM is the pacing mode of choice of
      patients with paroxysmal atrial tachyarrhythmias. With optimal programming,
      inappropriate mode switching and tracking of atrial tachyarrhythmias was very
      uncommon.

PMID- 9247525
TI  - Response to pacing at sites of isolated diastolic potentials during ventricular
      tachycardia in patients with previous myocardial infarction.
AB  - OBJECTIVES: The goal of this study was to determine whether isolated diastolic
      potentials (IDPs) recorded during ventricular tachycardia (VT) are generated in
      zones of slow conduction and whether the arcs of block that bound these zones of
      slow conduction are functional or anatomic in nature. BACKGROUND: No previous
      studies have systematically investigated the response to pacing during VT and
      sinus rhythm at sites where IDPs are recorded. METHODS: The study included 11
      patients with a previous infarction who underwent radiofrequency catheter
      ablation of 15 hemodynamically stable, sustained VTs and in whom an IDP that
      could not be dissociated from the VT was detected during mapping. RESULTS: Pacing
      during VT at the site where the IDP was recorded resulted in concealed
      entrainment in each of the 15 VTs. In 10 of the 15 VTs, an IDP was present during
      sinus rhythm at the same site at which a diastolic potential was recorded during
      VT. In nine VTs, the isolated potential occurred early in diastole; in these
      cases, the QRS configuration during pacing in the setting of sinus rhythm was
      different from that during VT. In six VTs, the isolated potential occurred later
      in diastole, and in these cases, the QRS configuration during pacing in the
      setting of sinus rhythm was the same as that during VT. CONCLUSIONS: Isolated
      diastolic potentials may often be generated in an area of slow conduction bounded
      by arcs of block that are anatomically determined and present during sinus
      rhythm.

PMID- 9247526
TI  - Pulmonary effect of amiodarone in patients with heart failure. The Congestive
      Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) Investigators
      (Veterans Affairs Cooperative Study No. 320).
AB  - OBJECTIVES: The purpose of this study was to evaluate the pulmonary effects of
      amiodarone in patients with heart failure, in those with chronic obstructive
      pulmonary disease (COPD) and in those undergoing a surgical procedure.
      BACKGROUND: Amiodarone has been known to cause pulmonary complications;
      especially in those with COPD and in those undergoing a surgical procedure.
      METHODS: Patients receiving vasodilator therapy for congestive heart failure were
      prospectively randomized to placebo or amiodarone at 800 mg/day for 14 days, 400
      mg/day for 50 weeks and then 300 mg/day thereafter. Chest X-ray film and
      pulmonary function tests with diffuse capacity of carbon monoxide (DLCO) were
      obtained at baseline and annually. The power to detect a 20% difference in DLCO
      at 1 year exceeded 90% in all patients and in those with COPD (two-sided alpha =
      0.05). The sample allowed a 75% power to detect pulmonary complications (1% vs.
      5%) between the two treatment groups. RESULTS: There was no difference in
      baseline characteristics between patients randomized to amiodarone (n = 269) or
      placebo (n = 250). The DLCO measurements at randomization were 18.3 +/- 6.9 and
      17.7 +/- 7.6 ml/min per mm Hg for the amiodarone and placebo groups, respectively
      (p = 0.3). At 1 and 2 years, DLCO measurements were 17.7 +/- 7.0 and 18.3 +/- 7.7
      ml/min per mm Hg for the amiodarone group and 17.9 +/- 7.2 and 18.2 +/- 7.2 for
      the placebo group, respectively. There were no significant differences between
      the groups, with corresponding p values of 0.73 ad 0.96 at years 1 and 2,
      respectively. Among patients with COPD, DLCO measurements at randomization were
      17.9 +/- 6.7 and 15.8 +/- 6.8 ml/min per mm Hg for the amiodarone and placebo
      groups, respectively. At years 1 and 2, DLCO measurements were 16.6 +/- 7.8 and
      17.8 +/- 9.5 ml/min per mm Hg for the amiodarone group and 16.5 +/- 6.6 and 16.3
      +/- 7.0 ml/min per mm Hg for the placebo group, with corresponding p values of
      0.95 and 0.48, respectively. There was no difference in survival free of
      noncardiac or perioperative deaths between patients assigned to amiodarone or
      placebo. Pulmonary fibrosis was diagnosed in four patients (1.1%) treated with
      amiodarone and in three patients (0.8%) receiving placebo. CONCLUSIONS: Our study
      shows that amiodarone can be safely used, with an acceptable pulmonary toxicity,
      in patients with heart failure.

PMID- 9247527
TI  - Differences between primary care physicians and cardiologists in management of
      congestive heart failure: relation to practice guidelines.
AB  - OBJECTIVES: This study was designed to characterize physician practices in the
      management of congestive heart failure (CHF) and to determine whether these
      practices vary by specialty and how they relate to guideline recommendations.
      BACKGROUND: Congestive heart failure is responsible for considerable mortality,
      morbidity and health care resource utilization. Although there have been
      important advances in the diagnostic evaluation and treatment of CHF, little
      information is available on physician practices in this area. METHODS: We
      surveyed physicians concerning their management of patients with CHF. The results
      were analyzed in multivariate models to determine the relation of diagnostic and
      treatment approaches to physician specialty, time since training, board
      certification and volume of patients with CHF. Surveys were sent to a sample of
      2,250 family and general practitioners (FP/GPs), internists and cardiologists.
      Responses were examined in relation to guidelines issued by the Agency for Health
      Care Policy and Research that had been released 9 months previously. RESULTS:
      Significant differences were found between physician groups with regard to each
      of the major guideline recommendations. For example, routine evaluation of left
      ventricular function, a point of emphasis in the guideline, is performed by 87%
      of cardiologists, but by only 77% of internists and 63% of FP/GPs (p < 0.001
      between groups). Angiotensin-converting enzyme inhibitors were used by
      cardiologists, internists and FP/GPs in 80%, 71% and 60% of patients with mild to
      moderate CHF, respectively (p < 0.001 between groups). Larger differences were
      reported in the prescribed dosages of these drugs and their use in patients with
      renal dysfunction. CONCLUSIONS: Cardiologists report practices more in conformity
      with published guidelines for CHF than do internists and FP/GPs. Because of the
      large numbers of patients with CHF and their substantial mortality, morbidity and
      cost of care, these differences may have a major impact on outcomes and health
      care costs.

PMID- 9247528
TI  - Insulin resistance in chronic heart failure: relation to severity and etiology of
      heart failure.
AB  - OBJECTIVES: We attempted to assess insulin sensitivity in patients with chronic
      heart failure (CHF) and its relation to disease severity. BACKGROUND: Peripheral
      muscular changes influence the progression of heart failure. This effect may be
      due to chronic disturbances of insulin and glucose metabolism that affect the
      energy status of skeletal and myocardial muscle. METHODS: We investigated insulin
      sensitivity in 79 men-38 patients with CHF, 21 patients with angiographic
      evidence of coronary artery disease without CHF and 20 healthy control subjects
      and assessed its relation to disease severity, etiology and hormonal status (all
      subjects had a similar age and body mass index). Insulin sensitivity was
      estimated by minimal modeling analysis of the glucose and insulin and profiles
      during a 0.5 g/kg body weight intravenous glucose tolerance test. RESULTS:
      Compared with control subjects, patients with CHF had similar mean fasting
      glucose but increased insulin levels (67 vs. 29 pmol/liter, p < 0.002) and a 58%
      reduced mean insulin sensitivity (2.01 vs. 4.84 min-1/pmol/ml x 10(5), p <
      0.0001). Peak oxygen consumption (VO2) (r = 0.63), fasting triglycerides (r = 
      0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity
      independently. Rest norepinephrine and epinephrine levels, left ventricular
      ejection fraction and heart failure etiology were not related to insulin
      sensitivity. Patients with coronary artery disease but no CHF had an intermediate
      mean insulin sensitivity (3.30 min-1/pmol/ml x 10(5) [-32%, p = 0.042 vs. control
      subjects; +113%, p = 0.0023 vs. patients with CHF due to ischemic heart
      disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006),
      triglycerides (p = 0.0023), fasting insulin (p = 0.0037) and the presence of CHF
      (p = 0.018) were independent predictors of impaired insulin sensitivity (adjusted
      joint R2 = 0.53, p < 0.0001). CONCLUSIONS: CHF is associated with marked insulin
      resistance, characterized by both fasting and stimulated hyperinsulinemia.
      Advanced heart failure (in terms of reduced peak VO2) is related to increased
      insulin resistance, but this is not directly mediated through ventricular
      dysfunction or increased catecholamine levels.

PMID- 9247529
TI  - Enhanced myocardial 18F-2-fluoro-2-deoxyglucose uptake after orthotopic heart
      transplantation assessed by positron emission tomography.
AB  - OBJECTIVES: We sought to assess the relation between glucose metabolism,
      myocardial perfusion and cardiac work after orthotopic heart transplantation.
      BACKGROUND: The metabolic profile of the transplanted cardiac muscle is affected
      by the lack of sympathetic innervation, impaired inotropic function, chronic
      vasculopathy, allograft rejection and immunosuppressive therapy. In relation to
      myocardial perfusion and cardiac work, glucose metabolism has not previously been
      studied in heart transplant recipients. METHODS: Regional myocardial blood flow
      (ml.min-1.g-1) and 18F-2-fluoro-2-deoxyglucose (18FDG) uptake rate (ml.s-1.g-1)
      were measured after an overnight fast in 9 healthy male volunteers (mean age +/-
      SD 32 +/- 7 years) and in 10 male patients (mean age 50 +/- 10 years) who had a
      nonrejecting heart transplant, normal left ventricular function and no
      angiographic evidence of epicardial coronary sclerosis. Measurements were made by
      using dynamic positron emission tomography (PET) with 15O-labeled water and
      18FDG, respectively. Heart rate and blood pressure were also measured for
      calculation of rate-pressure product. RESULTS: 18FDG uptake was similar in all
      heart regions in the patients and volunteers (intrasubject regional variably 12
      +/- 8% and 16 +/- 12%, respectively, p = 0.51). Regional myocardial blood flow
      was similarly evenly distributed (intrasubject regional variability 14 +/- 10%
      and 12 +/- 8%, respectively, p = 0.67). Mean 18FDG uptake and myocardial blood
      flow values for the whole heart are given because no regional differences were
      identified. 18FDG uptake was on average 196% higher in the patients than in the
      volunteers (2.90 +/- 1.79 x 10(-4) vs. 0.98 +/- 0.38 x 10(-4) ml.s-1.g-1, p =
      0.006). Regional myocardial blood flow and rate-pressure product were similarly
      increased in the patient group, but by only 41% (1.14 +/- 0.3 vs. 0.81 +/- 0.13
      ml.min-1.g-1, p = 0.008) and 53% (11,740 +/- 2,830 vs. 7,689 +/- 1,488, p =
      0.001), respectively. CONCLUSIONS: 18FDG uptake is homogeneously increased in
      normally functioning nonrejecting heart transplants. This finding suggests that
      glucose may be a preferred substrate in the transplanted heart. The magnitude of
      this observed increase is significantly greater than that observed for myocardial
      blood flow or cardiac work. In the patient group, the latter two variables were
      increased to a similar degree over values in control hearts, indicating a
      coupling between cardiac work load and myocardial blood flow. The
      disproportionate rise in 18FDG uptake may be accounted for by inefficient
      metabolic utilization of glucose by the transplanted myocardium or by the
      influence of circulating catecholamines, which may stimulate glucose uptake
      independently of changes in cardiac work load.

PMID- 9247530
TI  - Mechanism and location of atrial flutter in transplanted hearts: observations
      during transient entrainment from distant sites.
AB  - OBJECTIVES: This study was designed to elucidate the location and mechanism of
      typical atrial flutter in the transplanted heart. BACKGROUND: Although the F wave
      morphology in atrial flutter is similar in nontransplanted and transplanted
      hearts, the surgical incision needed for the atrial anastomosis may create a
      distinct electrophysiologic substrate of atrial flutter. METHODS: Entrainment
      from the lateral wall of the right atrium and interatrial septum was used to
      determine the location of atrial flutter in five patients with a transplanted
      heart and six patients with a nontransplanted heart. The difference between the
      first postpacing interval (FPPI) and the flutter cycle length (FCL) was used as
      an index of proximity to the circuit. RESULTS: In the transplant group, the FPPI
      was equal to the FCL at sites located close to the tricuspid annulus (TA); the
      mean differences (+/-SD) were 1 +/- 5 and -1 +/- 2 ms at the lateral wall and
      interatrial septum, respectively. However, from sites close to the surgical
      incision at the lateral wall and at the interatrial septum, these differences
      were significantly longer (29 +/- 12 and 27 +/- 9 ms, respectively, p < 0.05). In
      the nontransplant group, the FPPI was similar to the FCL at points in the lateral
      wall and interatrial septum close to the TA (mean difference 7 +/- 6 and 6 +/- 11
      ms, respectively) and at sites close to the crista terminalis (CT) in the lateral
      wall (mean difference 4 +/- 4 ms). However, in sites separated from the TA at the
      interatrial septum the difference was markedly longer (35 +/- 11 ms, p < 0.05).
      CONCLUSIONS: Atrial flutter in transplanted hearts may best be explained by
      macroreentry around the tricuspid ring. In non-transplanted hearts a different
      structure (perhaps the CT?) may be the basis for atrial flutter at the lateral
      wall.

PMID- 9247531
TI  - Anomalous origin of left coronary artery from pulmonary artery: recovery of left
      ventricular function after dual coronary repair.
AB  - OBJECTIVES: We reviewed our institutional experience with anomalous origin of the
      left coronary artery from the pulmonary artery (ALCAPA) after dual coronary
      repair to assess preoperative variables predictive of outcome, the time course
      for postoperative recovery of cardiac function, the short- and long-term
      complications and our experience with left ventricular assist devices (LVAD) in
      these patients. BACKGROUND: Outcome after surgical repair of ALCAPA remains
      incompletely defined. METHODS: The surgical records and echocardiograms of 42
      patients were reviewed. Left ventricular function was assessed by fractional
      shortening z-score (FSz) and stress-velocity index. RESULTS: The overall survival
      rate was 86%. All six patients who died were < 1 year old and died within 3 days
      of the operation. More severe preoperative mitral regurgitation (MR) was
      associated with increased mortality, but age, body surface area, preoperative FSz
      and end-diastolic dimension were not. We used an LVAD for 7 of 28 patients who
      underwent repair for ALCAPA since its introduction at our institution, with a
      survival of 5 of 7 patients. The degree of MR improved in 62% of patients and
      remained unchanged in 38%. Complications included supravalvar pulmonary stenosis
      (16 of 21 patients) and baffle leaks (11 of 21 patients) with the intrapulmonary
      baffling technique. Supravalvar pulmonary stenosis developed in 1 of 11 patients
      after direct coronary reimplantation. Left ventricular function became normalized
      in all 28 patients with follow-up past 1 year, regardless of preoperative FSz. Of
      13 patients who underwent serial postoperative echocardiography, the average time
      to normalization of function was 2 to 7 months. CONCLUSIONS: The degree of
      preoperative MR was predictive of outcome, whereas the severity of preoperative
      cardiac dysfunction and ventricular dilation were not. Mild and moderate MR
      tended to improve without mitral valvuloplasty. Complete recovery from myocardial
      dysfunction is expected after dual coronary repair of ALCAPA.

PMID- 9247532
TI  - Hemodynamic data and survival in children with pulmonary hypertension.
AB  - OBJECTIVES: Using data from a multi-institutional data base, we sought to
      determine whether hemodynamic data predict duration of survival in children with
      primary or secondary pulmonary hypertension. BACKGROUND: Lung transplantation is
      a therapeutic option for children with pulmonary hypertension. Appropriate timing
      of lung transplantation requires reliable methods of predicting duration of
      survival in potential candidates. METHODS: A regional data base was used to
      obtain cardiac catheterization data on 50 children with mean pulmonary artery
      pressure (mPAP) > 25 mm Hg and indexed pulmonary resistance (Rp) > 4.5 Wood
      units. Data on survival were obtained from the participating centers. RESULTS:
      There were 15 patients without congenital heart disease (group 1) and 35 patients
      with congenital heart disease (group 2) for analysis. Actuarial survival at 1, 2
      and 5 years was 86%, 69% and 69% in group 1 and 88% and 77% in group 2,
      respectively (p = NS). Hemodynamic variables that predicted survival on
      univariate analysis were mean right atrial pressure (mRAP) (p < 0.0001), mPAP (p
      = 0.034), Rp (p < 0.0001) and pulmonary flow (p = 0.003), as well as a variable
      that we generated-mRAP x Rp (p < 0.0001). On multivariate stepwise logistic
      regression analysis, mRAP x Rp was independently related to survival. A model
      using mRAP x Rp allows for the estimation of probability of death at 1 and 2
      years after catheterization. CONCLUSIONS: Hemodynamic variables can predict
      survival in children with pulmonary hypertension in the presence or absence of
      congenital heart defects. This information can be used to determine the optimal
      timing of listing for lung transplantation.

PMID- 9247533
TI  - Dissolution of thrombotic arterial occlusion by high intensity, low frequency
      ultrasound and dodecafluoropentane emulsion: an in vitro and in vivo study.
AB  - OBJECTIVES: We examined the effectiveness of the microbubbles of an echo contrast
      agent, dodecafluoropentane (DDFP) emulsion, to enhance low frequency ultrasound
      clot disruption in vitro and in vivo. BACKGROUND: Ultrasound is reported to
      facilitate clot dissolution, and microbubbles could theoretically enhance
      ultrasound clot dissolution by augmenting cavitational effects. METHODS:  IN
      VITRO STUDIES: The disruption rate of fresh human clots by ultrasound (24 kHz,
      2.9 W/cm2) was examined in saline and DDFP emulsion. In vivo studies: Using a
      rabbit iliofemoral thrombotic occlusion model, recanalization rate and
      histopathologic findings were compared among groups treated with DDFP emulsion
      alone, transcutaneous ultrasound (20 kHz, 1.5 W/cm2) alone and with DDFP emulsion
      and ultrasound combined. RESULTS: The ultrasound clot disruption rate was
      significantly (p < 0.01) increased, from 72 +/- 18% (mean +/- SD) in saline to 98
      +/- 4% in DDFP emulsion in 3 min in vitro. No vessel was recanalized by DDFP
      emulsion alone (0%), and only a single artery was patent after ultrasound
      treatment alone (9%). In contrast, 82% of iliofemoral arteries were
      angiographically recanalized after ultrasound treatment with DDFP emulsion.
      Histologically, the patent arteries had only minimal focal mural thrombus, with
      no evidence of vessel wall damage. However, substantial damage was observed in
      rabbit dermis and subcutaneous tissue. CONCLUSIONS: 1) DDFP emulsion, an echo
      contrast agent, significantly enhances the clot-disrupting effect of low
      frequency ultrasound in vitro and in an in vivo rabbit iliofemoral occlusion
      model. 2) This simple combination therapy has potential for clinical application
      in patients with thrombotic arterial occlusions.

PMID- 9247534
TI  - Preservation of endogenous antioxidant activity and inhibition of lipid
      peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E,
      lovastatin and amlodipine.
AB  - OBJECTIVES: We sought to document the common mechanisms of the antiatherogenic
      effects of the cholesterol-lowering hydroxy-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitor lovastatin, the dihydropyridine Ca2+ blocker amlodipine and
      the antioxidant vitamin E. BACKGROUND: Vitamin E, HMG-CoA reductase inhibitors
      and Ca2+ blockers each inhibit atherosclerosis in hypercholesterolemic animals.
      METHODS: New Zealand White rabbits were fed regular chow (Group A), chow with 1%
      cholesterol (Group B), 1% cholesterol diet plus lovastatin (Group C), 1%
      cholesterol diet plus vitamin E (Group D) or 1% cholesterol diet plus amlodipine
      (Group E) for 12 weeks. The extent of aortic atherosclerosis was measured by
      planimetry of the sudanophilic area. Malondialdehyde (MDA) and superoxide
      dismutase (SOD) in blood were measured as indexes of lipid peroxidation and
      antioxidant activity, respectively. RESULTS: Group A rabbits showed no
      atherosclerosis, whereas Group B rabbits had 17.4 +/- 9.3% (mean +/- SD) of the
      aorta covered with atherosclerosis, and Groups C, D and E rabbits had
      significantly less atherosclerosis. Plasma SOD activity was lower in Group B than
      in Group A (6.9 +/- 1.1 vs. 12.8 +/- 1.5 U/ml, p < 0.01) and was preserved in the
      groups given lovastatin, vitamin E or amlodipine with a high cholesterol diet.
      The serum MDA level was higher in Group B rabbits than Group A rabbits (12.1 +/-
      2.6 vs. 1.2 +/- 0.1 nmol/ml, p < 0.01) and increased minimally in rabbits given
      lovastatin, vitamin E or amlodipine with a high cholesterol diet. In in vitro
      experiments, both lovastatin and amlodipine preserved SOD activity and reduced
      the oxidizability of low density lipoproteins by rabbit leukocytes. CONCLUSIONS:
      This study suggests that a reduction in lipid peroxidation and preservation of
      SOD may be common mechanisms of antiatherosclerotic effects of lovastatin,
      vitamin E and amlodipine.

PMID- 9247535
TI  - Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia
      induced cardiomyopathy.
AB  - OBJECTIVES: This study sought to determine whether the canine model of
      tachycardia-induced heart failure (HF) is an effective model for sudden cardiac
      death (SCD) in HF. BACKGROUND: Such a well established HF model that also
      exhibits arrhythmias and SCD, along with repolarization abnormalities that could
      trigger them, may facilitate the study of SCD in HF, which still eludes effective
      treatment. METHODS: Twenty-five dogs were VVI-paced at 250 beats/min for 3 to 5
      weeks. Electrocardiograms were obtained, and left ventricular endocardial
      monophasic action potentials (MAPs) were recorded at six sites at baseline and
      after HF. Weekly Holter recordings were made with pacing suspended for 24 h.
      RESULTS: Six animals (24%) died suddenly, one with Holter-documented polymorphic
      ventricular tachycardia (VT). Holter recordings revealed an increased incidence
      of VT as HF progressed. Repolarization was significantly (p < 0.05) prolonged, as
      indexed by a corrected QT interval (mean [+/-SD] 311 +/- 25 to 338 +/- 25 ms) and
      MAP duration measured at 90% repolarization (MAPD90) (181 +/- 19 to 209 +/- 28
      ms), and spatial MAPD90 dispersion rose by 40%. We further tested whether CsCl
      inhibition of repolarizing K+ currents, which are reportedly downregulated in HF,
      might preferentially prolong the MAPD90 in HF. With 1 mEq/kg body weight of CsCl,
      MAPD90 rose by 86 +/- 100 ms in dogs with HF versus only 28 +/- 16 ms in control
      animals (p = 0.002). Similar disparities in CsCl sensitivity were observed in
      myocytes isolated from normal and failing hearts. CONCLUSIONS: Tachycardia
      induced HF exhibits malignant arrhythmia and SCD, along with prolonged,
      heterogeneous repolarization and heightened sensitivity to CsCl at chamber and
      cellular levels. Thus, it appears to be a useful model for studying mechanisms
      and therapy of SCD in HF.

PMID- 9247536
TI  - Extension of hemorrhage after reperfusion of occluded coronary artery: contrast
      echocardiographic assessment in dogs.
AB  - OBJECTIVES: The aim of this study was to elucidate the progression of intramural
      hemorrhage complicated by reperfusion with the use of myocardial contrast
      echocardiography. BACKGROUND: Although hemorrhagic infarction is known to occur
      in ischemia followed by reperfusion, its onset and sequence have not been well
      characterized. METHODS: In 20 anesthetized dogs, 3-h occlusion of the left
      circumflex-coronary artery was followed by reperfusion. The area at risk during
      coronary occlusion was approximately 25%. Myocardial contrast echocardiogram was
      examined, and the time-intensity curves for both ischemic and nonischemic areas
      were obtained at baseline, at 3 min after reperfusion and then at 15-min
      intervals until 90 min after reperfusion. The wall thickness of both areas was
      also measured. RESULTS: Gross hemorrhage in the reperfused areas was observed in
      five dogs (Group H) but not in seven dogs (Group NH). All wall segments were
      opacified at 3 min after reperfusion in both groups. However, the contrast defect
      spread significantly with time after reperfusion in Group H but not in Group NH
      (18.7 +/- 3.4% and 3.3 +/- 1.8%, respectively, at 90 min after reperfusion p <
      0.005). The wall of the risk area at 90 min after reperfusion had thickened to
      1.3 times baseline thickness in Group H but was unchanged in Group NH. The other
      eight dogs were excluded from study because of fatal arrhythmias or the existence
      of collateral circulation during coronary occlusion. CONCLUSIONS: Both
      progression of the contrast defect area on myocardial contrast echocardiography
      and a gradual thickening of the wall with reperfusion are characteristic of
      hemorrhagic infarction.

PMID- 9247537
TI  - Academic medicine--rearranging deck chairs on the Titanic.

PMID- 9247538
TI  - Characterization of the putative alpha subunit of a heterotrimeric G protein in
      rice.
AB  - A recombinant protein with a cDNA that encodes the putative alpha subunit of a
      rice heterotrimeric G protein was synthesized in Escherichia coli and purified.
      The recombinant protein (rGrice alpha) with an apparent molecular mass of 45 kDa
      was bound with guanosine 5'-(3-O-thio)triphosphate with an apparent association
      constant (kapp) of 0.36. The protein also hydrolyzed GTP and its kcat was 0.44.
      rGrice alpha was ADP-ribosylated by activated cholera toxin. Monoclonal
      antibodies raised against rGrice alpha reacted with a 45 kDa polypeptide
      localized in the plasma membrane of rice seedlings. The peptide map of this
      polypeptide after digestion with V8 protease was identical to that of rGrice
      alpha. A 45 kDa polypeptide in the plasma membrane, as well as rGrice alpha, was
      ADP-ribosylated by activated cholera toxin. The GTPase activity of the plasma
      membrane was stimulated 2.5-fold by mastoparan 7 but not mastoparan 17. These
      properties were similar to those of the alpha subunits of heterotrimeric G
      proteins in animals, suggesting that the putative alpha subunit is truly the
      alpha subunit itself.

PMID- 9247539
TI  - Characterization of SaMADS D from Sinapis alba suggests a dual function of the
      gene: in inflorescence development and floral organogenesis.
AB  - SaMADS D gene of Sinapis alba was isolated by screening a cDNA library from young
      inflorescences with a mixture of MADS-box genes of Antirrhinum majus (DEF, GLO,
      SQUA) as probe. Amino acid sequence comparison showed a high degree of similarity
      between the SaMADS D and AGL9, DEFH200, TM5, FBP2 and DEFH 72 gene products.
      Analysis of the SaMADS D gene expression by in situ hybridization reveals a novel
      expression pattern for a MADS-box gene and suggests a dual function for this
      gene: first, as a determinant in inflorescence meristem identity since it starts
      to be expressed directly beneath the inflorescence meristem at the time of
      initiation of the first floral meristem, is no longer expressed in the
      inflorescence meristem forced to revert to production of leafy appendages, and is
      expressed again when the reverted meristem resumes floral meristem initiation,
      and, second, as an interactor with genes specifying floral organ identity since
      it is expressed in the floral meristem from the stage of sepal protrusion.

PMID- 9247540
TI  - Molecular cloning and biochemical characterization of carbonic anhydrase from
      Populus tremula x tremuloides.
AB  - A leaf cDNA library from hybrid aspen, Populus tremula x tremuloides, was
      constructed. From this two different cDNA clones, denoted CA1a and CA1b, encoding
      a chloroplastic carbonic anhydrase (CA) were isolated and DNA sequenced. Analysis
      of the deduced amino acid sequences showed that the isolated CAs belong to the
      beta-CA family, and have identities around 70% to other dicotyledonous plant CAs.
      The two hybrid aspen cDNA clones display a high nucleotide sequence identity,
      only 12 nucleotides differ. Since only one gene copy of this soluble
      chloroplastic CA is present in the nuclear genome, we postulate that the two
      isolated cDNA clones are alleles. Northern blot hybridization revealed a CA
      transcript of ca. 1300 bases, 140 bases shorter than in pea. Western and northern
      blot hybridizations on crude protein extracts and on total RNA, respectively,
      isolated from stem and leaves, showed that hybrid aspen CA is expressed
      specifically in the leaf under the growth conditions used. Based on the deduced
      amino acid sequence, the mature hybrid aspen CA enzyme subunit has a molecular
      mass of 24.8 kDa. The enzyme was over-expressed in Escherichia coli, and purified
      by affinity chromatography. Biochemical characterization showed that the protein
      structure and the CO2-hydration activity are similar to the pea enzyme. Molecular
      characterization of a CA from a perennial plant has not previously been
      performed, and it demonstrates that both the structure and activity of hybrid
      aspen CA resembles CAs from annual plants.

PMID- 9247541
TI  - Expression of a novel-type small proline-rich protein gene of alfalfa is induced
      by 2,4-dichlorophenoxiacetic acid in dedifferentiated callus cells.
AB  - Differential screening of a cDNA library of 2,4-dichlorophenoxiacetic acid (2,4
      D)-treated alfalfa (Medicago sativa) callus tissues resulted in the isolation of
      a 571 bp cDNA clone (MsPRP5) encoding for a proline-rich protein (84 amino acids)
      with a specific repeat unit of TPVLPPRK/RGRPPPVPP. In addition, a characteristic
      amino acid block (PPVYK) previously found in other proline-rich proteins also
      occurs in the C-terminal region of MsPRP5. At the N-terminal, a signal peptide
      similar to leader sequences of extracellular proteins can be predicted. According
      to the northern analysis, the corresponding gene is not expressed or is weakly
      expressed in differentiated vegetative organs and somatic embryos. However the
      accumulation of MsPRP5 mRNA is auxin concentration-dependent in dedifferentiated
      callus tissue. An increase in the amount of steady-state mRNA was detected
      already 20 min after auxin shock (100 microM 2,4-D). Maximum expression was
      observed at 24-48 h in the presence of 2,4-D. Elevated expression was also found
      in cells recovering after heat shock and wounding stress. In synchronized alfalfa
      cells, the transcript level of MsPRP5 gene fluctuated during cell cycle
      progression with peaks in G1/S phase cells. Considering the structural features
      and expression properties of MsPRP5, this clone may represents a new type of
      proline-rich protein gene which responds to hormonal shock and some other
      stresses as well.

PMID- 9247542
TI  - Bnm1, a Brassica pollen-specific gene.
AB  - cDNA and genomic clones of a new pollen-specific gene, Bnm1, have been isolated
      from Brassica napus cv. Topas. The gene contains an open reading frame of 546 bp
      and a single intron of 362 bp. A comparison of the deduced amino acid sequence
      with sequences in data banks did not show similarity with known proteins.
      Northern blot analysis of developing pollen showed that Bnm1 mRNA was first
      detected in bicellular pollen and accumulated to higher levels in tricellular
      pollen. Bnm1 mRNA was not detected in leaves, stems, roots, pistils, seeds or
      pollen-derived embryos. RNA in situ hybridization of whole flower buds confirmed
      that Bnm1 was pollen-specific and expressed late in development. A promoter
      fragment of the Bnm1 gene fused to the gusA reporter gene yielded similar
      patterns of tissue specificity and developmental regulation in transgenic B.
      napus cv. Westar plants; however, the promoter was also active during the early
      stages of pollen development. The Bnm1 gene, cloned in this study, was derived
      from the A genome of the allotetraploid species B. napus (AACC). Southern blot
      analysis indicated that sequences similar to the Bnm1 gene were found in both A
      and C Brassica genomes. Related sequences were found in all 10 members of the
      Brassiceae tribe examined, but were not present in all tribes of the Brassicaceae
      family.

PMID- 9247543
TI  - Transcription of genes for conglutin gamma and a leginsulin-like protein in
      narrow-leafed lupin.
AB  - The expression of genes encoding conglutin gamma and a leginsulin-like protein
      has been examined in narrow-leafed lupin, Lupinus angustifolius L. Conglutin
      gamma is a homologue of basic 7S globulin (Bg), the insulin and leginsulin
      binding protein from soybean. Accumulation of conglutin gamma mRNA, as assessed
      by northern assays and reverse-transcription PCR, was tightly regulated both
      spatially and temporally in lupin plants and was detected almost exclusively in
      developing seeds. Similar tissue and temporal specificity was demonstrated when
      1.8 kb of the promoter region from the conglutin gamma gene was used to drive the
      expression of a beta-glucuronidase reporter gene in transgenic plants. In stably
      transformed tobacco the conglutin gamma promoter produced strong, temporally
      regulated and seed-specific expression of the reporter gene which was localised
      to the embryo tissues and to a layer of cells adjacent to the seed coat. A
      truncated 0.29 kb promoter fragment produced much reduced levels of expression
      and a loss of embryo specificity. Leginsulin-like mRNA was similarly detected in
      lupins only in developing seeds. The leginsulin-like gene detected in L.
      angustifolius showed 96% sequence identity to leginsulin from soybean within the
      280 bp region amplified from lupin by PCR. The results demonstrate that both
      components of a Bg-leginsulin putative signal transduction pathway are present in
      the seeds of lupin.

PMID- 9247545
TI  - cDNA structure and expression patterns of a low-temperature-specific wheat gene
      tacr7.
AB  - The low-temperature (2 degrees C)-specific wheat cDNA, pTACR7, represents a gene
      designated tacr7 from hard red winter wheat (HRWW; Triticum aestivum L. cv.
      Winoka). The term low-temperature-specific (LTS) is used because tacr7 is not
      induced by ABA or stresses such as salt, dehydration, and heat. pTACR7 was
      isolated by RT-PCR with mRNA from wheat crown tissue, the oligonucleotide primers
      derived from the barley cognate pHVCR8 (GenBank accession number L28091). Based
      on the deduced amino acid sequence, TACR7 is highly hydrophobic, with a single
      transmembrane domain and an amino acid bias for leucine (19%). Thus, the encoded
      protein TACR7 is unique among low-temperature-regulated wheat proteins described
      in the literature. Analysis of steady-state levels of tacr7 transcripts (630 nt)
      showed accumulation in wheat seedlings, crown tissue, and callus cultures after
      transfer from control (25 degrees C) to low temperature (2 degrees C). No
      detectable transcripts were observed by northern blot hybridization with pTACR7
      probe from seedling or callus treated with ABA, salt, dehydration, or heat
      stress. tacr7 transcripts accumulated during 2 degrees C exposure to a greater
      amount in a freeze-resistant HRWW (FR; SDmut 16029) than in a freeze-susceptible
      HRWW (FS; SDmut 16169) crown tissue, with the largest difference between
      genotypes being 30% +/- 3% at 3 weeks.

PMID- 9247544
TI  - A drought-stress-inducible histone gene in Arabidopsis thaliana is a member of a
      distinct class of plant linker histone variants.
AB  - We have isolated and characterized a gene, His1-3, encoding a structurally
      divergent linker histone in Arabidopsis thaliana. Southern and northern
      hybridization data indicate that A. thaliana expresses three single-copy linker
      histone genes, each encoding a structurally distinct variant. H1-3 is a
      considerably smaller protein (167 amino acids with a mass of 19.0 kDa) than any
      other described linker histone from higher eukaryotes. We examined the expression
      of His1-3 at the RNA and protein levels and found that it is induced specifically
      by water stress. In contrast, expression of His1-1, His1-2 and His4 appear
      unaffected by water stress. Furthermore, the primary structure of the protein
      possesses distinct characteristics that are shared with another drought-inducible
      linker histone, H1-D, isolated from Lycopersicon pennellii. Based on structural
      characteristics of the deduced protein and its inducible expression, we
      hypothesize that H1-3 and H1-D are linker histone variants that have specialized
      roles in the structure and function of plant chromatin and therefore they can be
      considered to be members of a unique subclass of plant histones. Immunoblotting
      with an antibody produced against a short polypeptide in the conserved domain of
      this subtype indicates that similar proteins may exist in other plants.

PMID- 9247547
TI  - GUS expression in Arabidopsis directed by 5' regions of the pea metallothionein
      like gene PsMTA.
AB  - Upstream sequences (including the first seven codons) of a metallothionein (MT)
      like gene from pea, PsMTA, were fused to GUS and introduced into Arabidopsis.
      High-level GUS expression was detected in the roots of plants grown on MS medium,
      except in regions proximal to the root apex. There was precise delineation of the
      root-shoot boundary. In soil-grown plants there was low GUS expression and this
      was absent from the more mature regions of the roots. In the aerial tissues of
      soil-grown plants, GUS expression was restricted to hydathodes, stipules,
      expanding cotyledons and the following senescent tissues: leaves, cotyledons,
      petals, sepals, filaments, stigmas, nectaries and siliques. A 298 bp region was
      shown to be required for GUS expression in roots but not for expression in
      vegetative aerial tissues of plants grown on MS medium. This region contains
      predicted ethylene-responsive elements (EREs) but similar patterns of GUS
      expression were detected in etr1 seedlings. GUS expression was significantly
      higher in roots exposed to 500 nM copper, but this increase was small in
      proportion to expression in roots exposed to 50 nM copper.

PMID- 9247548
TI  - Cuphea wrightii thioesterases have unexpected broad specificities on saturated
      fatty acids.
AB  - Cuphea wrightii A. Gray is an herbaceous annual that accumulates 30% caprate
      (10:0) and 54% laurate (12:0) in seed storage lipids. We investigated the role of
      acyl-acyl carrier protein (ACP) thioesterases (TE) in acyl chain-length
      regulation in C. wrightii. Two embryo-derived cDNAs, encoding the TEs Cw FatB1
      and Cw FatB2, were isolated. Both proteins were detected in developing embryos
      and mature seeds but not in other tissues, suggesting involvement in seed oil
      synthesis. Although expected to be 10:0/12:0-ACP-specific, these genes produced a
      broad range of fatty acids (12:0, 14:0, and 16:0) in transgenic Arabidopsis with
      the greatest accumulation at 14:0. Cw FatB2 transformants also accumulated small
      amounts of 10:0. Because C. wrightii accumulates only ca. 5% 14:0 and ca. 2%
      16:0, we tested the possibility that gene dosage effects might significantly
      alter the overall kinetics of the pathway. Phenotypic comparisons of progeny
      segregating for the transgenes individually and in a hybrid population
      demonstrated that increased enzyme pools in vivo had a minor effect on diverting
      fatty acid production to shorter chains. We propose that Cw FatB1 and Cw FatB2
      may be necessary but not sufficient determinants of the C. wrightii phenotype.

PMID- 9247549
TI  - Characterization of a lily tapetal transcript that shares sequence similarity
      with a class of intracellular pathogenesis-related (IPR) proteins.
AB  - This study addresses isolating and characterizing a cDNA clone corresponding to a
      tapetum-specific transcript, designated as PR-10a from Lilium longiflorum. Anther
      ontogeny is histologically divided into three consecutive phases. The first
      encompasses early proliferative stages and differentiation of the locules. The
      second concerns microspore development from the onset of meiosis through
      microspore maturation. The final phase involves pollen maturation, originating
      with microspore mitosis through pollen formation. The lily PR-10a transcript is
      anther-specific and temporally expressed only at the phase of microspore
      development during which the tapetal cells become polarized, highly secretory,
      and exhibit loss of cell walls. The maximal level of PR-10a transcript coincides
      strictly with the peak of tapetal secretory function. Comparing mRNA and cDNA
      insert sizes reveals that PR-10a is close to full-length. Sequence analysis
      demonstrates similarity between the predicted lily PR-10a and asparagus AoPR1
      protein, potato pSTH2 and pSTH21 proteins, parsley PcPR1 and PcPR3 proteins, bean
      PvPR1 and PvPR2 proteins, lupin L1R18B protein, pea 149 protein and a family of
      major allergens including Cor a 1 of hazel, Car b 1 of hornbeam, Aln g 1 of
      alder, Bet v 1 of birch and Api g 1 of celery. To the authors' knowledge, this is
      the first reported organ/tissue-specific IPR protein.

PMID- 9247550
TI  - Tetracycline-dependent activation of an upstream promoter reveals transcriptional
      interference between tandem genes within T-DNA in tomato.
AB  - Tomato plants stably expressing the tetR gene were transformed with the beta
      glucuronidase (GUS) gene and an le20 antisense construct both under the control
      of the Triple-Op promoter. Induction of GUS mRNA and le20 antisense RNA in leaves
      was demonstrated in response to tetracycline. le20 antisense induction was also
      demonstrated in fruit. Activation of the Triple-Op promoter reduced expression of
      the downstream hygromycin phosphotransferase II (hptII) gene. Transcriptional
      interference was therefore observed between tandem genes within T-DNA. Such
      interference may occur in other T-DNAs, but would not be readily observed without
      an upstream promoter with controllable activity.

PMID- 9247551
TI  - Molecular genetic and biochemical analysis of Brassica napus proliferating cell
      nuclear antigen function.
AB  - A cDNA encoding the proliferating cell nuclear antigen (PCNA) from Brassica napus
      (oilseed rape) was shown to complement the lethal deletion mutation in the PCNA
      gene (delta POL30) of Saccharomyces cerevisiae. We provide unequivocal evidence
      that the B. napus PCNA can perform all the essential functions of the yeast PCNA
      in DNA replication, although some species-specific differences may exist. In
      addition, the B. napus PCNA expressed as a fusion polypeptide with glutathione S
      transferase (GST) was shown to stimulate the activity and processivity of two
      delta-like DNA polymerases from wheat in vitro. These experiments provide direct
      biochemical evidence that the B. napus PCNA may function as an auxiliary factor
      in plant cell DNA replication.

PMID- 9247552
TI  - Percutaneous balloon mitral valvuloplasty.
AB  - Percutaneous balloon mitral valvuloplasty, first performed by Inoue in 1982, was
      a rational progression from 4 decades of experience with the blunt surgical
      dilatation technique of closed mitral commissurotomy. As with surgical
      commissurotomy, balloon valvuloplasty relieves mitral stenosis by the splitting
      of fused commissures. A series of studies have shown that balloon valvuloplasty
      achieves excellent acute hemodynamic results in close to 90% of patients, with a
      typical 100% increase in mitral valve area. Over the past 15 years since Inoue's
      first patient, a number of other techniques have been introduced and largely
      discarded in favor of the original approach. Advances have occurred along the
      lines of improved noninvasive assessment of mitral valve disease, which have
      allowed better case selection and prediction of outcome. Follow-up series have
      shown sustained improvement, with modest rates of complications and restenosis.
      Comparative studies have shown that balloon valvuloplasty is as effective and
      safe as surgical commissurotomy, and is a cost-effective procedure of first
      choice in ideal patients.

PMID- 9247553
TI  - Balloon aortic valvuloplasty.
AB  - Balloon aortic valvuloplasty is a percutaneous, therapeutic option for patients
      with severe aortic stenosis, yet the effectiveness of this procedure is dependent
      on the morphology of the stenotic aortic valve and the respective mechanism of
      dilation. In younger patients with congenital aortic stenosis, acute and
      intermediate-term results are good. However, in adult patients, in whom
      degenerative aortic stenosis is the most common cause, the acute clinical and
      hemodynamic benefits of balloon aortic valvuloplasty are not lasting, as
      restenosis occurs in most patients within 6 months. Sympatomatic relief for
      adults undergoing balloon aortic valvuloplasty is only apparent in patients with
      normal left ventricular function, who generally are also candidates for aortic
      valve replacement. Furthermore, the long-term survival for adults after balloon
      aortic valvuloplasty is similar to the natural history of untreated severe aortic
      stenosis. In this article, the mechanism of balloon aortic valvuloplasty, as well
      as its clinical and hemodynamic effects, are reviewed in the context of the
      different morphological types of aortic stenosis. In addition, two large
      registries of adult patients treated with balloon aortic valvuloplasty provide
      important information regarding the acute and long-term results of this procedure
      and are reviewed.

PMID- 9247554
TI  - Percutaneous therapy of structural heart disease: pediatric disease.
AB  - Interventional therapy of congenital heart lesions at cardiac catheterization has
      greatly increased during the past decade. At the authors' institution, the
      frequency of such procedures among catheterizations has increased from 5% to more
      than 60%. The variety of lesions so treated continues to expand and equipment
      continues to improve. These procedures may be divided into 2 groups, namely (1)
      those involving balloon dilation of stenotic valves and vessel obstructions with
      stent placement being increasingly used in the latter and (2) those involving
      occlusion of lesions with (a) coils, such as aortopulmonary collaterals, patent
      ductus arteriosi and coronary artery fistulae and (b) umbrella devices, such as
      atrial and ventricular septal defects. These have replaced surgery as the initial
      procedure of choice in many lesions including valvar pulmonary and aortic
      stenoses, and postoperative aortic coarctation in young patients. In addition,
      use of the double-umbrella device even in noncongenital lesions appears
      promising.

PMID- 9247555
TI  - Changing concepts in the determination of valvular stenosis.
AB  - The cardiovascular system can be characterized as a series of chambers connected
      by tubes and orifices. The circulatory physiology of this system is governed by
      hydrodynamic laws. The first application of hydrodynamics to stenotic valve
      orifices was by Gorlin and Gorlin in 1951, with direct measurement of
      transvalvular pressure gradients in the catheterization laboratory. The relative
      imprecision of fluid-filled catheters was corrected by the introduction of high
      fidelity micromanometric catheters in 1978. Echocardiography, which directly
      measures blood velocity, currently provides an accurate and widely applied tool
      for hemodynamic evaluation. Measured changes in blood velocity can derive
      pressure gradients previously measured by cardiac catheterization. In the
      clinically important range of determinations, there is excellent correlation
      between echocardiographic methods and the Gorlin formula for calculating valvular
      stenosis. Although noninvasive evaluation of heart valve stenosis has become
      standard, the same physical laws apply as in the 1950s, and practitioners need to
      be aware of the limitations of the various methods of hemodynamic calculation.

PMID- 9247557
TI  - Coronary artery aneurysm: a review.
AB  - Coronary artery aneurysm is defined as coronary dilatation which exceeds the
      diameter of normal adjacent segments or the diameter of the patient's largest
      coronary vessel by 1.5 times. This is an uncommon disease which has been
      diagnosed with increasing frequency since the advent of coronary angiography. The
      incidence varies from 1.5% to 5% with male dominance and a predilection for the
      right coronary artery. Atherosclerosis accounts for 50% of coronary aneurysms in
      adults. Reported complications include thrombosis and distal embolization,
      rupture and vasospasm. The natural history and prognosis remains obscure.
      Controversies persist regarding the use of surgical or medical management. The
      authors recommend surgery based on the severity of associated coronary stenosis
      rather than the mere presence of aneurysm. Medical therapy is indicated for the
      majority of patients and consists of antiplatelet and anticoagulant medication.

PMID- 9247556
TI  - Cocaine-induced myocardial ischemia and infarction: pathophysiology, recognition,
      and management.
AB  - As cocaine abuse has become widespread, it has been associated with various
      cardiovascular complications, including angina pectoris, myocardial infarction,
      and sudden cardiac death. Cocaine's principal effects on the cardiovascular
      system are mediated via alpha-adrenergic stimulation and include (1) an increase
      in the determinants of myocardial oxygen demand (heart rate and systemic arterial
      pressure), and (2) a concomitant decrease in myocardial oxygen supply (caused by
      vasoconstriction of the epicardial coronary arteries). beta-adrenergic blocking
      agents may exacerbate cocaine-induced coronary arterial vasoconstriction, thereby
      increasing the magnitude of myocardial ischemia. In contrast, nitroglycerin and
      verapamil reverse cocaine-induced hypertension and coronary arterial
      vasoconstriction; therefore, they are the agents of choice in treating patients
      with cocaine-associated chest pain.

PMID- 9247559
TI  - Variant mouse lymphoma cells with modified response to interferon demonstrate
      enhanced immunogenicity.
AB  - We have previously developed an experimental model for the xenogenization of
      malignant lymphoma. From highly tumorigenic S49 mouse lymphoma cells that
      proliferate in suspension culture (designated T-25), we selected variant clones
      that grew as an adherent monolayer (designated T-25-Adh) and were non-tumorigenic
      in syngeneic mice. Furthermore, priming of syngeneic hosts with T-25-Adh cells
      protected them against subsequent challenges with the tumorigenic T-25 cells.
      Several lines of evidence have indicated that antigens of an endogenous mouse
      mammary tumor virus (MMTV) are involved in the immunogenicity of T-25-Adh cells.
      Since interferon (IFN) is known to affect retroviral assembly and maturation on
      the cell membrane, we have studied the effects of IFN on endogenous MMTV-related
      structures, as well as on the immunogenicity of T-25-Adh cells. We observed that
      mouse alpha and beta interferons affect the morphogenesis of intracellular MMTV
      related precursors in the immunogenic T-25-Adh cells, but not in tumorigenic T-25
      cells. From T-25-Adh cells we selected variants that were either high responders
      or low responders to the above-mentioned interferon effect. The high-response
      variants were significantly more protective against tumorigenic T-25 cells than
      the low-response variants. Involvement of MMTV-related antigens in the immune
      response of the host to T-25-Adh cells was further suggested by immunoelectron
      microscopical analysis, demonstrating that antisera from mice, immunized with T
      25-Adh cells, interacted specifically with cell-surface MMTV budding particles.
      These findings indicate a novel method for xenogenization of lymphoma cells by
      IFN. Since endogenous retroviruses are present in all tissues of the mouse, this
      approach might be applicable to a wide variety of tumors.

PMID- 9247558
TI  - Amiodarone therapy in chronic heart failure and myocardial infarction: a review
      of the mortality trials with special attention to STAT-CHF and the GESICA trials.
      Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina.
AB  - Amiodarone appears to reduce sudden death in patients with left ventricular
      dysfunction resulting from an acute MI or a primary dilated cardiomyopathy,
      particularly if complex ventricular arrhythmias are present. Amiodarone's
      beneficial effect on mortality in these patients could be unrelated to its
      antiarrhythmic effects. Multiple factors could account for the improvement in
      mortality such as the drug's antiischemic effects, neuromodulating effects, its
      effect on left ventricular function and on heart rate. Moreover, patients with LV
      dysfunction who have survived an episode of sudden death would potentially
      benefit from amiodarone therapy. Future trials are needed to determine the
      precise subsets(s) of patients who would benefit from the drug and the most
      efficacious dosing regimen for the drug. Based on available data, amiodarone is
      the only antiarrhythmic agent which has not been shown to increase mortality in
      patients with chronic heart failure.

PMID- 9247560
TI  - Efficiency of T cell triggering by anti-CD3 monoclonal antibodies (mAb) with
      potential usefulness in bispecific mAb generation.
AB  - T cell triggering can be achieved by monoclonal antibodies (mAbs) specific for
      the CD3/TcR complex. In the presence of appropriate costimulation and/or
      progression factors, such triggering permits the generation of effector cells for
      immunotherapy protocols involving the redirection of T cell lysis against tumor
      cells by mAbs bispecific for anti-CD3/anti-tumor cells (bs-mAbs). Focusing our
      analysis on the clinically relevant bs-mAb OC/TR, we found that bs-mAbs generated
      with the same anti tumor specificity, but two other anti-CD3 mAbs, TR66 and OKT3,
      have the same and a significantly lower lytic potential, respectively, compared
      with that of OC/TR. To evaluate the relevance of the anti-CD3 component, we
      examined several anti-CD3 mAbs with respect to binding parameters and the ability
      to trigger T lymphocytes. Competitive binding assays suggested that all anti-CD3
      mAbs recognized the same or overlapping epitopes, although mAbs BMA030 and OC/TR
      bound with lower avidity than did alpha CD3 (the bivalent anti-CD3 mAb produced
      by the hybrid hybridoma OC/TR). TR66 and OKT3, as determined by measurement of
      the affinity constants. In all lymphocyte populations examined, which included
      resting peripheral blood mononuclear cells (PBMC), activated PBMC and T cell
      clones, OKT3, BMA033 and OC/TR failed to mobilize Ca2+ without cross-linking,
      whereas alpha CD3, in both murine and murine-human chimeric versions, TR66 and
      BMA030, did not require cross-linking. The ability to induce CD3 modulation was
      associated in part with the induction of Ca2+ fluxes. Despite the differences in
      the behavior of these mAbs in triggering the events that precede proliferation,
      all of them ultimately led to expression of the IL-2 receptor and to
      proliferation in T cells in the presence of accessory cells. Our data suggest
      that anti-CD3 mAbs that bind more rapidly (strong Ca2+ mobilizers) and more
      tightly under physiological conditions are good candidates for retargeting T
      cells in the bs-mAb clinical application.

PMID- 9247561
TI  - Induction of multiple anti-c-erbB-2 specificities accompanies a classical
      idiotypic cascade following 2B1 bispecific monoclonal antibody treatment.
AB  - The bispecific monoclonal antibody (bsmAb) 2B1, targeting the extracellular
      domain of c-erbB-2, the protein product of the HER-2/neu proto-ocogene, and Fc
      gamma RIII (CD16), expressed by human natural killer cells, neutrophils and
      differentiated monocytes, mediates the specific cytotoxic activity of these
      effector cells to tumor cells. A group of 24 patients with c-erbB-2
      overexpressing tumors were treated with intravenously administered 2B1 in a phase
      I clinical trial and followed after treatment to evaluate the diversity and
      extent of the 2B1-induced humoral immune responses. As expected, 17 of 24
      patients developed human anti-(murine Ig) antibodies (HAMA) to whole 2B1 IgG in a
      range from 100 ng/ml to more than 50000 ng/ml; 10 of these patients (42%) had
      strong (at least 1000 ng/ml) HAMA responses, some of which were still detectable
      at day 191. These responses were usually associated with similar reactivity to
      the F(ab')2 fragments of the parental antibodies 520C9 (anti-c-erbB-2) and 3G8
      (anti-CD16). We sought evidence of an idiotypic cascade induction, indicating a
      prolonged specific treatment-induced effect on at least one selected target of
      2B1. Using competition-based enzyme-linked immunosorbent assays, specific anti
      idiotypic antibodies (Ab2) were detectable against 520C9 in 11 patients and
      against 3G8 in 13 patients. Peak anti-idiotypic antibodies generally occurred 3-5
      weeks from treatment initiation, with a downward trend thereafter. There was a
      statistically significant correlation among the induction of significant HAMA
      responses, anti-idiotypic antibody production and the development of antibodies
      to c-erbB-2. The anti-c-erbB-2 responses, which were distinct from anti-anti
      idiotypic (Ab3) antibodies, were detected in the post-treatment sera of 6/16
      patients examined. No obvious correlation could be made between the development
      of humoral immune responses, the dose received, and the clinical response. Future
      investigation involving 2B1 therapy will concentrate on investigating an
      association of these humoral responses to any c-erbB-2-specific cellular
      responses. Manipulations of 2B1 therapy effects that augment immunity to c-erbB-2
      could provide additional avenues for immunotherapy with this and other bispecific
      antibodies.

PMID- 9247562
TI  - Gene transfer of a hybrid interleukin-1 beta gene to B16 mouse melanoma recruits
      leucocyte subsets and reduces tumour growth in vivo.
AB  - Interleukin(IL)-1 differs from most other cytokines in its lack of a signal
      sequence. This results in intracellular retention of the immature proform. The
      release of IL-1 has been shown to be restricted predominantly to activated
      monocytes and macrophages and to be associated with apoptosis of the producer
      cell. These features have limited the investigation of IL-1 in early immune
      responses. In order to study the biological effects of local IL-1 beta release
      during an antitumour immune response, we used B16 mouse melanoma cells transduced
      with mature human IL-1 beta cDNA constructs. To obtain a released form of human
      IL-1 beta (ssIL-1 beta), the signal sequence from the related IL-1 receptor
      antagonist was ligated to the cDNA that encoded the mature form of IL-1 beta.
      When cells of the poorly immunogenic B16 melanoma cell line were transduced with
      IL-1 beta by retroviral infection, high levels of the protein were detected
      intracellularly, whereas cells transduced with IL-1 beta containing the signal
      sequence secreted most of their protein. The in vitro growth of the melanoma
      cells was unaffected by the IL-1 beta or ssIL-1 beta gene transfer. In contrast,
      the in vivo subcutaneous tumour growth of the ssIL-1 beta-transduced B16 cells in
      syngeneic C57BL/6 mice was significantly reduced compared with the IL-1 beta- and
      the mock-transduced controls. Immunohistochemical analysis revealed the
      infiltration of macrophages to be strong in B16/ssIL-1 beta, moderate in B16/IL-1
      beta and minimal in control tumours. Furthermore, a moderate infiltration of CD4+
      cells and of scattered dendritic cells was detected in B16/ssIL-1 beta tumours
      whereas very few or no CD4+ cells and dendritic cells were seen in the B16/IL-1
      beta or control tumours. Following in vivo growth, all the tumours upregulated
      ICAM-1 on their cell surfaces. However, the percentage of ICAM-1-expressing cells
      was two- to four-fold higher in B16/ssIL-1 beta tumours compared to the control.
      The data suggest that IL-1 beta acts in vivo, either directly or indirectly, as a
      chemotactic factor for monocytes, T helper cells and dendritic cells. This
      supports IL-1 beta having a regulatory effect on tumour growth when locally
      released in the tumour area.

PMID- 9247563
TI  - The participation of the Fas-mediated cytotoxic pathway by natural killer cells
      is tumor-cell-dependent.
AB  - Cytotoxic T lymphocytes and natural killer (NK) cells kill target cells by two
      main mechanisms, namely, the perforin/granzymes and the Fas ligand (Fas-L)
      pathways. The preferential activation of either of these two mechanisms by target
      cells is not known. This study examined whether various NK stimuli regulate
      preferentially the perforin/granzyme or the Fas pathways during the NK-cell
      mediated cytotoxic reaction (NK-CMC). Purified peripheral-blood-derived NK cells
      were stimulated with interleukin-2 (IL-2), IL-12, or interferon alpha (IFN alpha)
      and their response was analyzed by the reverse transcriptase/polymerase chain
      reaction (RT-PCR) for NK-associated gene expression and by the 51Cr-release assay
      for cytotoxic function. RT-PCR data revealed that the perforin, granzyme A and
      granzyme B mRNAs were constitutively expressed in unstimulated NK cells and the
      level of perforin mRNA was augmented following activation. IL-2 enhanced the
      level of Fas-L mRNA in NK cells; however, the Fas-L level was much lower than
      that obtained in activated T cells. NK-CMC against Fas-sensitive cells was
      examined in the presence of neutralizing anti-(Fas antigen receptor) (Fas-R)
      antibody (ZB-4) or EGTA/Mg2+, which inhibits the perforin/granzyme pathway but
      not the Fas Fas-L interaction. The human colon adenocarcinoma HT-29 cells were
      sensitized to anti-Fas-R antibody (CH-11) cytotoxicity following treatment with
      IFN gamma. NK-CMC against untreated HT-29 cells was completely inhibited by
      EGTA/Mg2+ and was unaffected by ZB-4, while both EGTA/Mg2+ and ZB-4 partially
      inhibited NK-CMC against IFN gamma-treated HT-29 cells. Similar findings to those
      obtained with untreated NK cells were observed with NK cells stimulated with IL
      2, IL-2 plus IL-12 or IFN alpha. In contrast to IFN gamma-treated HT-29 cells,
      the neutralizing anti-Fas antibody ZB-4 did not inhibit NK-CMC against Fas
      sensitive U937, CEM or Jurkat tumor cells. These findings demonstrate that the
      Fas pathway is involved in NK-CMC against certain target cells but not all.
      Further, the data demonstrate that activation of NK cells by IL-2, IL-2 plus IL
      12 or IFN alpha does not preferentially modulate the Fas-L-mediated killing by NK
      cells.

PMID- 9247564
TI  - Interleukin-4 is effective in restoring cytotoxic T cell activity that declines
      during in vivo progression of a murine B lymphoma.
AB  - We previously reported [Chakrabarti et al. (1992) Cell Immunol 142:54; 144:455]
      that, in a murine B lymphoma model 2C3, idiotype (Id)-specific CD8+ cytotoxic T
      lymphocytes (CTL) are generated in mice following hyperimmunization with
      irradiated tumor cells, and that they are effective in tumor rejection. The
      present study reveals that 2C3-specific CTL are also induced in spleens during
      tumor progression, but are not sustained. At the early stage of tumor growth, the
      splenic T cells following a 5-day incubation in vitro with killed 2C3 tumor
      targets, produce high levels of cytokines, namely interleukin-4 (IL-4), IL-10 and
      interferon gamma (IFN gamma). Their cytotoxic T lymphocyte (CTL) activity and
      cytokine levels, except IL-2, sharply decline at the late stage when the mice are
      increasingly moribund. Although the decline in cytokine level is also evident
      with CD4+ T cells, a precipitous and concurrent decrease occurs primarily in the
      IL-4 level with both CD4+ and CD8+ T cells of late-tumor-bearing animals (TBA).
      Study with the unseparated splenocytes also reveals that sevenfold less IL-4 is
      produced at the late stage. Furthermore, the cytotoxicity of CTL from late TBA
      can be effectively restored by addition of supernatants from the splenocyte
      culture of early TBA, or by IL-4, but not by IFN gamma and IL-10. In addition,
      only IL-4-activated CD8+ T cells from the late TBA are found, by Winn assay, to
      be protective in vivo. Thus it appears that IL-4, required to sustain antitumor
      CTL activity, is consumed by T and possibly other cells at the late stage of
      tumor growth, thereby compromising host immunity against the tumor. We contend
      that induction or maintenance of protective immunity depends not only on the
      tumor antigen but also on the specific cytokine milieu in a tumor-bearing host.

PMID- 9247565
TI  - Tunnelled central venous catheters yield a low incidence of septicaemia in
      interleukin-2-treated patients.
AB  - A retrospective study on the incidence of catheter-related complications and
      catheter indwelling time (tCI) during treatment with continuous interleukin-2 (IL
      2) infusion in patients with metastatic renal cell cancer, who were equipped with
      tunnelled central venous catheters (CVC). A group of 72 patients were treated
      with IL-2-based immunotherapy. Two induction treatment cycles of 35 days each
      were used. Treatment consisted of IL-2 as a continuous intravenous infusion
      (c.i.v.) with lymphokine-activated killer cells and interferon alpha
      intramuscularly. A tunnelled CVC was inserted at the start of treatment and was
      kept in place for the duration of the therapy or until the occurrence of
      complications. Out of 72 CVC, 30 (42%) functioned uneventfully for a median tCI
      of 64 days. In another 12 clinically uncomplicated cases (16%), catheter tips
      were positive in routine culture after a median tCI of 33 days. In 18 patients
      (25%), CVC-related infections were noted, including 8 (11%) local tunnel
      infections and 10 (14%) septic episodes. These complications occurred at a median
      tCI of 28 and 20 days respectively. In 15 (83%) of these 18 catheter infections,
      Staphylococcus aureus was isolated, whereas in the remaining 3 (17%)
      Staphylococcus epidermidis was found. Subclavian vein thrombosis was noted in 12
      (17%) CVC at a median tCI of 31 days: 5 (36%) of these were diagnosed in the
      first 14 patients. This prompted us to administer prophylactic heparin 15,000
      i.u. c.i.v. daily during IL-2 treatment. Thereafter the incidence of thrombosis
      dropped to 7 (12%) in the subsequent 58 CVC inserted (P = 0.03). In conclusion,
      in contrast to previous reports on the high incidence of CVC-related septicaemia
      and thrombosis, we observed a relatively low incidence of these complications,
      which we ascribe to the use of tunnelled catheters and prophylactic heparin.

PMID- 9247566
TI  - Deletion of alloantigen-reactive thymocytes as a mechanism of adult tolerance
      induction following intrathymic antigen administration.
AB  - Direct injection of foreign antigen into the adult thymus is a potent route of
      antigen delivery for the induction of tolerance in vivo. In this report, we
      demonstrate that tolerance to C57BL/10 (H2b/BL10) alloantigens can be induced in
      CBA/Ca (H2k/CBA) mice by intrathymic (IT) administration of BL10 spleen
      leukocytes coincident with transient peripheral immunomodulation of CD4+ T cells
      using a depleting anti-CD4 monoclonal antibody. T cell receptor (TCR) transgenic
      mice (BM3.6; H2k) expressing a CD8-independent TCR specific for H2Kb were used as
      recipients to facilitate investigation of the mechanisms responsible for
      tolerance induction by allowing visualization of events in the thymus following
      IT injection. IT administration of 5 x 10(7) BL10 spleen leukocytes and
      concomitant transient peripheral T cell depletion in BM3.6 mice resulted in a
      substantial H2Kb-specific deletion of transgenic-TCR+ (tg-TCR) thymocytes which
      was dependent on the level of tg-TCR expression. IT deletion and the failure to
      export CD8+ T cells to the peripheral lymphoid organs correlated with the
      induction of tolerance to H2Kb; TCR transgenic mice that had received IT
      injection of BL10 splenocytes and peripheral T cell depletion accepted a H2Kb+
      cardiac allograft indefinitely. Analysis of tolerant BM3.6 mice revealed that
      there were low numbers of CD8+ T cells in the periphery giving rise to a
      substantially reduced reactivity in vitro despite the fact that no donor cells or
      IT deletion were observed in the thymi of the majority of tolerant mice. These
      results demonstrate for the first time that IT injection of foreign alloantigen
      into an adult thymus results in the deletion of thymocytes expressing a TCR
      specific for the injected alloantigen and suggest that this is an important
      mechanism of tolerance induction following IT injection of alloantigen in vivo.
      Furthermore, analysis of tolerant TCR-transgenic mice suggests that IT deletion
      is not required for the maintenance of tolerance, and that peripheral mechanisms
      enforce continued hyporesponsiveness to H2Kb following transplantation.

PMID- 9247568
TI  - Ras activation leads to cell proliferation or apoptotic cell death upon
      interleukin-2 stimulation or lymphokine deprivation, respectively.
AB  - Lymphokine-dependent cells undergo apoptosis upon lymphokine withdrawal. We
      describe that lymphokine deprivation of the interleukin (IL)-2- or IL-4-dependent
      mouse T cell line TS1 alpha beta induces Ras activation which plays a role in
      programmed cell death, since blocking Ras activity reduces the induction of
      apoptosis. Induction of apoptosis by lymphokine deprivation can be prevented by
      expression of the Bcl-2 protein. Rescue from cell death by IL-2 also promotes Ras
      activation, but, in contrast to lymphokine withdrawal, stimulates Bcl-2
      expression. IL-4-induced cell survival is Ras- and Bcl-2 independent. These
      results are compatible with a model in which cell proliferation requires the
      simultaneous induction of at least two pathways which act in combination to
      prevent cell death.

PMID- 9247567
TI  - Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors,
      but not with the processing of p105/NF-kappa B1 in T cells.
AB  - The transcription factor NF-kappa B controls the induction of numerous cytokine
      promoters during the activation of T lymphocytes. Inhibition of T cell activation
      by the immunosuppressants cyclosporin A (CsA) and FK506 exerts a suppressive
      effect on the induction of these NF-kappa B-controlled cytokine promoters. We
      show for human Jurkat T leukemia cells, as well as human and mouse primary T
      lymphocytes, that this inhibitory effect is accompanied by an impaired nuclear
      translocation of the Rel proteins c-Rel, RelA/p65 and NF-kappa B1/p50, whereas
      the nuclear appearance of RelB remains unaffected. CsA does not interfere with
      the synthesis of Rel proteins, but prevents the inducible degradation of
      cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell
      activation. CsA neither inhibits the processing of the NF-kappa B1 precursor p105
      to p50, nor does it "stabilize" the C-terminal portion of p105, I kappa B gamma,
      which is degraded during p105 processing to mature p50. These results indicate
      that CsA interferes with a specific event in the signal-induced degradation of I
      kappa B alpha and I kappa B beta, but does not affect the processing of NF-kappa
      B1/p105 to p50.

PMID- 9247569
TI  - Germ-line transcription and methylation status of the TCR-J alpha locus in its
      accessible configuration.
AB  - We have generated two in vivo mouse models to study the regulation of DNA
      accessibility to the V(D)J recombinase machinery in the T cell receptor (TCR)-J
      alpha locus. In recombination activating gene (RAG)-deficient mice, both
      injection of a TCR-beta chain transgene (RTB mice) or anti-CD3-epsilon treatment
      in vivo (RT3 mice) lead to the same phenotype with homogeneous thymocyte
      populations blocked at the CD4+ CD8+ double positive (DP) stage. At this
      developmental stage, the TCR-alpha rearrangements are about to start, and the TCR
      J alpha locus is frozen in an accessible but yet unrearranged configuration in
      these mice. We show high level of TCR-alpha germ-line transcription in thymocytes
      from RTB and RT3 mice. Transcripts are skewed towards the 5' end of the TCR-J
      alpha locus, and the T early alpha (TEA) sterile transcript is predominant and
      therefore provides a useful marker for the TCR-J alpha locus opening. Analysis of
      the DNA methylation status reveals a global surmethylation of the TCR-J alpha
      locus in the thymus in comparison with non-lymphoid cells in these mice. We
      propose that hypermethylation of the locus could precede a progressive
      demethylation, providing a specific protective and regulatory role in the
      rearrangement events.

PMID- 9247570
TI  - B lineage-restricted rearrangement of a human Ig kappa transgene.
AB  - To study the control of immunoglobulin kappa light chain gene rearrangement, we
      generated transgenic mice carrying a germ-line human kappa minilocus (HK)
      containing the J kappa-proximal V gene, V kappa IV, the V-J intergenic region,
      the five J kappa segments and the C kappa gene. This construct includes the
      intronic, but not the 3' kappa enhancer. Rearrangement of the HK transgene was
      found to be lymphoid specific and restricted to the B cell lineage.
      Quantification of kappa gene rearrangement in pre-B cell lines established from
      HK transgenic mice showed that, like endogenous kappa genes, rearrangement of the
      transgene is repressed in mu-negative early B cell precursors. These results
      indicate that rearrangement of the HK transgene is subjected to the same B/T cell
      and developmental regulation as V kappa-J kappa rearrangement at the endogenous
      locus. Comparison with an unrearranged kappa transgenic construct lacking the V-J
      intergenic region, suggests that this region, or elements associated with the
      proximal V gene, may act to restrict kappa gene rearrangement to the B cell
      lineage.

PMID- 9247571
TI  - Normal B cells fail to secrete interleukin-12.
AB  - Interleukin-12 is a key regulatory cytokine produced by antigen-presenting cells
      (APC) which drives the development of interferon-gamma (IFN-gamma)-producing
      cells and promotes cell-mediated immunity. Following subcutaneous immunization
      with protein antigen in adjuvant, dendritic cells (DC) but not small nor large B
      cells in immune lymph nodes express antigenic complexes and secrete substantial
      amounts of bioactive IL-12 p75 upon antigen-specific interaction with T cells. We
      have analyzed secretion of IL-12 p40 and p75 by cell populations enriched in DC,
      macrophages or B cells in response to nonspecific stimulation or to interaction
      with antigen-specific CD4+ cells. These APC populations do not produce IL-12
      constitutively but, upon stimulation with heat-fixed Staphylococcus aureus and
      IFN-gamma, IL-12 p40 and p75 are secreted by DC and macrophages, whereas B cells
      fail to produce IL-12. B cells also fail to secrete IL-12 in response to
      stimulation with LPS and IFN-gamma. Co-culture with CD4+ T hybridoma cells and
      antigen induces IL-12 secretion by DC. Up-regulation of IL-12 secretion by
      interaction with antigen-specific CD4+ T cells is abrogated by anti-class II
      monoclonal antibodies (mAb), by soluble CD40 molecules and by anti-CD40 ligand
      mAb, demonstrating a positive feedback between T cells and DC mediated by TCR
      peptide/class II and by CD40-CD40 ligand interactions. Expression of class II and
      CD40 molecules is comparable in B cells and DC, and both APC types activate CD4+
      T cells. Yet, even upon interaction with antigen-specific T cells, B cells fail
      to secrete IL-12. The capacity of B cells to present antigen but not to secrete
      IL-12 may explain their propensity to selectively drive T helper type 2 cell
      development.

PMID- 9247572
TI  - An amphibian CD3 homologue of the mammalian CD3 gamma and delta genes.
AB  - T cell receptor (TCR) genes have been identified in representatives of both
      cartilaginous and bony vertebrates. The CD3 chains that serve as signal
      transducing elements of the TCR complex in mammals have been defined to a limited
      extent in birds. In these studies a CD3 homologue was identified in an amphibian
      representative, Xenopus laevis, using degenerate oligomer primers designed from
      conserved regions of avian and mammalian CD3 gamma/delta subunits. The reverse
      transcriptase polymerase chain reaction amplified product of Xenopus splenocyte
      RNA was then used to isolate full-length cDNA clones from a splenic library. When
      employed as probes, the cDNA clones hybridized with a 1-kb mRNA transcript in
      Xenopus T cells, but not in other cell types. Comparison of the deduced amino
      acid sequence indicated a similar degree of homology with mammalian and avian CD3
      gamma and delta chains. Genomic analysis indicated that the Xenopus CD3 molecule
      is encoded by five exons, a structure resembling the mammalian CD3 delta gene
      rather than the seven exon CD3 gamma gene. Southern blot analysis and sequencing
      of the 5' flanking region failed to yield evidence of a related Xenopus gene.
      This amphibian CD3 gene thus appears to represent an ancestral form of the
      mammalian CD3 gamma and delta genes.

PMID- 9247573
TI  - On the mechanisms by which transforming growth factor-beta 2 alters antigen
      presenting abilities of macrophages on T cell activation.
AB  - Peritoneal exudate cells (PEC) incubated with antigen in the presence of
      transforming growth factor-(TGF)-beta 2 selectively suppress delayed
      hypersensitivity and IgG2a antibody production when injected intravenously into
      naive syngeneic recipients. In this study, we have examined in vitro the effects
      of TGF-beta 2 on the antigen presenting abilities of PEC to activate DO11.10 T
      cells that express a transgenic T cell receptor that recognizes ovalbumin peptide
      fragment 323-339 in the context of I-Ad. PEC were pretreated overnight with TGF
      beta 2, washed extensively, then co-cultured with DO11.10 T cells in the presence
      of native OVA or P323-339. We found that TGF-beta 2-treated PEC induced the
      production of the T helper type 2 (Th2) cytokine, interleukin-4 (IL-4), but
      unlike untreated PEC, were unable to stimulate the Th1 cytokines, IL-2 and
      interferon-gamma (IFN-gamma). Furthermore, TGF-beta 2 was produced in an
      autocrine fashion by TGF-beta 2-treated PEC and was responsible for this shift to
      a Th2 response. This conclusion was supported by the following results. First,
      TGF-beta 2-treated PEC were found to express much more TGF-beta 1 and TGF-beta 2
      mRNA than untreated PEC. Second, TGF-beta 2-treated PEC secreted large amounts of
      TGF-beta including its mature form. Third, addition of neutralizing anti-TGF-beta
      2 antibodies, but not neutralizing anti-TGF-beta 1 antibodies, restored the
      ability of antigen-pulsed, TGF-beta 2-pretreated PEC to stimulate DO11.10 T cells
      to secrete IL-2 and IFN-gamma. These results indicate that antigen-presenting
      cells that encounter antigen in a TGF-beta-enriched environment (e.g., in the
      eye) shift responding native T cells toward Th2 responses by producing TGF-beta
      during antigen presentation.

PMID- 9247574
TI  - Lack of correlation between rejection of tumor cells co-expressing interleukin-2
      and B7.1 and vaccine efficiency.
AB  - Genetically modifying tumor cells to express a variety of cytokines such as
      interleukin-2 (IL-2) or the co-stimulatory molecule B7.1 leads to increased
      immunogenicity and reduced tumorigenicity of tumors in several models with T
      cells involved in the process. We have previously reported decreased
      tumorigenicity of the murine plasmacytoma J558L [major histocompatibility complex
      (MHC) class I+ and class II-] expressing IL-2 or B7.1. When systemic immunity was
      analyzed, immunization with either J558-IL2 or J558-B7.1 cells generated moderate
      protection against unmodified J558L tumor cells, comparable to immunization with
      a tumor cells/adjuvant Corynebacterium parvum mixture. In this study, we asked
      whether the co-expression of IL-2 and B7.1 in tumor cells would augment vaccine
      potency, cytotoxic T lymphocyte (CTL) activity and protective immunity. Rejection
      of single IL-2 or B7.1 or co-transfected IL-2/B7.1 cells occurred in most
      syngeneic animals but not in T cell-deficient nude mice, thus confirming that T
      cells were required for tumor rejection. We knew from previous experiments that
      CD8+ T cells were responsible for rejection. Surprisingly, immunization with J558
      IL2/B7.1 cells followed by challenge with parental J558L caused a reduction in
      systemic protection as compared to J558-B7.1 or J558-IL2 alone. We examined the
      mechanism underlying this unexpected result: 6 days after injection of J558
      IL2/B7.1 cells, tumor were nearly completely destroyed and were almost devoid of
      CD8+ cells, while CD8+ cells were increased in both IL-2- and B7.1-transfected
      tumors. In addition, immunization with J558-IL2/B7.1 tumors had an adverse effect
      on the generation of CTL. Mice immunized with J558-B7.1 and to a lesser extent
      J558-IL2 cells mounted a CTL response against J558L cells while, in contrast, no
      CTL activity could be detected in mice immunized with J558-IL2/B7.1, thus showing
      a correlation between the absence of CTL activity and the lack of in vivo
      protection. We demonstrate that "hyperstimulation" of the immune response by
      genetically modified cancer vaccines can have adverse effects on tumor immunity,
      even though the mechanism is not yet completely understood.

PMID- 9247575
TI  - A role for Th2 cytokines in the suppression of CD8+ T cell-mediated graft
      rejection.
AB  - A major histocompatibility complex (MHC) class I-specific T cell receptor (TCR)
      transgenic mouse was used to study classical-type transplantation tolerance in
      the adult. Engraftment of MHC class I-incompatible bone marrow and tolerance to
      donor-type skin grafts were obtained using dimethylmyeleran (DMM) as a
      myeloablative agent and a non-depleting anti-CD8 monoclonal antibody (mAb) as the
      sole immunosuppressant. Surprisingly, bone marrow engraftment was facilitated by
      host CD4+ T cells, a subset normally considered unable to reject class I MHC
      incompatible grafts. A combination of mAb to interleukins (IL)-4 and -10
      antagonized the "permissive" effects of host CD4+ T cells, indicating a possible
      role for Th2-type immunoregulation that can act on CD8+ T cells in this form of
      transplantation tolerance. The fate of graft-reactive T cells was monitored using
      anti-clonotypic antibodies. It was observed that bone marrow engraftment then led
      to peripheral deletion of mAb-blockaded, clonotype+ CD8+ T cells.

PMID- 9247576
TI  - Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor
      alpha-mediated shock.
AB  - Cell surface components of pathogens, such as lipopolysaccharide (LPS), are an
      important signal for receptor-mediated activation of immune cells. Here we
      demonstrate that DNA of gram-positive and gram-negative bacteria or certain
      synthetic oligonucleotides displaying unmethylated CpG-motifs can trigger
      macrophages in vitro to induce nuclear translocation of nuclear factor-kappa B,
      accumulate tumor necrosis factor (TNF)-alpha mRNA and release large amounts of
      TNF-alpha. In vivo these events culminate in acute cytokine-release syndrome
      which includes systemic but transient accumulation of TNF-alpha. D-Galactosamine
      (DGalN)-sensitized mice succumb to lethal toxic shock due to macrophage-derived
      TNF-alpha resulting in fulminant apoptosis of liver cells. LPS and a specific
      oligonucleotide synergized in vivo as measured by TNF-alpha-release, suggesting
      that macrophages integrate the respective signals. The ability of macrophages to
      discriminate and to respond to bacterial DNA with acute release of pro
      inflammatory cytokines may point out an important and as yet unappreciated
      sensing mechanism for foreign DNA.

PMID- 9247577
TI  - Complex CD44 splicing combinations in synovial fibroblasts from arthritic joints.
AB  - CD44 is a broadly expressed cell surface glycoprotein which is the major cell
      surface receptor for the glycosaminoglycan, hyaluronan. In humans, alternative
      splicing of up to 9 variant exons (v2-v10) into CD44 mRNA, together with post
      translational modification via glycosylation and chondroitin sulfate attachment
      has the potential of generating a large number of CD44 isoforms. Insertion of
      these various exons has the potential to change the functional capacities of the
      molecule and has implications in disease. We have analyzed CD44 splice variant
      expression in cultured VCAM-1-positive synovial fibroblasts isolated from
      patients with osteo- or rheumatoid arthritis and from normal synovium. Rheumatoid
      and osteoarthritic tissue express CD44 splice variants at the cell surface level.
      At the mRNA level exons v3, v6, v7, v8, v9 and v10 were detected in different
      splicing combinations. Rheumatoid tissue showed high expression, osteoarthritic
      tissues showed great variation. In contrast, non-inflamed tissue showed no
      splicing events. Our results indicate that the nature of CD44 splice variant
      expression may be linked to the inflammatory state of the synovial joint.

PMID- 9247578
TI  - Protein disulfide isomerase is the dominant acceptor for peptides translocated
      into the endoplasmic reticulum.
AB  - Peptides derived from cytosolic protein degradation are translocated into the
      lumen of the endoplasmic reticulum (ER) by the transporter associated with
      antigen processing (TAP). In the ER, class I molecules bind the peptides fitting
      to their respective motifs and present them on the cell surface to CD8+ T
      lymphocytes. However, most TAP-translocated peptides are not expected to bind to
      the class I molecules present in a particular cell. Recently, we have
      demonstrated that TAP-translocated peptides containing a photoreactive
      phenylalanine analogue can be cross-linked to two luminal ER-resident proteins:
      with low efficiency to the stress protein gp96 and with high efficiency to a 60
      kDa protein (Lammert, E. et al., Eur. J. Immunol. 1997. 27: 923). Both proteins
      have also been labeled specifically by TAP-translocated peptides conjugated to a
      different photoreactive group (Marusina, K. et al., Biochemistry 1997. 36: 856).
      Here, we show that the 60-kDa peptide-binding protein is identical to the
      multifunctional protein disulfide isomerase (PDI). Since PDI is the only luminal
      ER-resident protein that is labeled by the photoreactive peptides with high
      efficiency, it might represent the dominant acceptor for TAP-translocated
      peptides.

PMID- 9247579
TI  - Analysis of HLA class Ib gene expression in male gametogenic cells.
AB  - We have investigated mRNA expression for nonclassical MHC class I genes (HLA-E,
      F,-G) in human gametogenic cells. Testicular tissue was treated by collagenase
      and the resulting cell suspension was further purified by fractionation on
      Percoll gradients in a two-step procedure. Three gametogenic cell fractions were
      analyzed: purified heterogenous suspension of gametogenic cells, fraction of
      round spermatids and fraction of elongated spermatids. Total RNA isolated from
      each cell population was subjected to both reverse transcriptase/polymerase chain
      reaction and Northern blot analysis using oligonucleotides specific for HLA-E, -F
      and -G. Both method gave similar results. We have found a considerable level of
      HLA-E mRNA, very low amounts of reamplified cDNA for HLA-F and both a complete
      lack of mRNA and reamplified cDNA for the HLA-G gene in the analyzed gametogenic
      cell fractions. Additionally, we have localized HLA-E molecules on the cells of
      the adluminal compartment within seminiferous tubules using immunostaining with
      monoclonal antibodies specific for HLA-E heavy chain followed by confocal
      microscopy analysis. The unique expression pattern of HLA class I antigens in the
      male gonad could play an important role in an efficient protection against an
      autoimmunological attack toward germ cells.

PMID- 9247580
TI  - Antigen-specific T cell receptor antagonism by antigen-presenting cells treated
      with the hemolysin of Listeria monocytogenes: a novel type of immune escape.
AB  - We have examined the influence of listeriolysin O (LLO), the hemolysin secreted
      by the pathogenic bacterium Listeria monocytogenes, on major histocompatibility
      complex class II-dependent T cell activation. Stimulation of T cells by native
      antigens but not by peptides is inhibited upon pretreatment of antigen-presenting
      cells (APC) with LLO. Experiments presented here reveal that this inhibition is
      not due to a lack in processing of antigen by APC but is the result of an
      irreversible inactivation of T cells that recognize antigen on LLO-treated APC.
      Incubation of mixtures of two different T cells where only one antigen was
      presented on LLO-treated APC suggested that T cell inactivation is antigen
      specific. The inactivation was dominant and could be observed even in the
      presence of amounts of synthetic peptides that normally lead to T cell responses.
      This condition is reminiscent of the T cell inhibition observed when antagonistic
      and stimulatory peptides are added to APC at the same time. Our results thus
      reveal a novel type of interference by pathogens with antigen presentation and T
      cell stimulation that could give the pathogen a decisive advantage in
      dissemination and disease.

PMID- 9247581
TI  - Patterns of lymphokine secretion amongst mouse gamma delta T cell clones.
AB  - Although the patterns of lymphokine (LK) secretion by CD4 and CD8 alpha beta T
      cells have been extensively studied, the question of whether gamma delta T cells
      display patterns of restricted LK production and whether these patterns are the
      same as seen in conventional alpha beta T cells has not been previously
      addressed. In this study we generated panels of gamma delta T cell clones from
      normal C57BL/6 and BALB/c mice using a lectin-driven system and compared their
      patterns of secretion of nine LK with those of CD4 and CD8 alpha beta T cell
      clones generated in the same system. The results showed that gamma delta T cell
      clones displayed nonrandom patterns of highly restricted LK production with a
      strong bias towards the production of type 1 LK. The dominant pattern was one of
      high level secretion of interferon-gamma and tumor necrosis factor (TNF), with
      variable production of interleukin (IL)-2, and little or none of the type 2 LK IL
      4, IL-5, IL-6, and IL-10. This pattern differed significantly from that of CD4
      Th1 clones in that gamma delta clones showed a striking deficiency in the
      production of IL-3 and granulocyte/macrophage colony-stimulating factor. A small
      subset of gamma delta clones displayed a novel pattern, in which the only LK
      produced in substantial quantity were TNF and variable amounts of IL-2. The bias
      of gamma delta T cells towards type 1 LK production was not an artefact
      associated with cloning because bulk populations of splenic gamma delta T cells
      behaved in the same way, even when activated in the presence of high
      concentrations of IL-4.

PMID- 9247582
TI  - Tumor necrosis factor (TNF) receptor type 1 (p55) is a main mediator for TNF
      alpha-induced skin inflammation.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine
      that elicits a large number of biological effects, including inflammatory and
      immunoregulatory responses. Biological activities of TNF-alpha are mediated by
      two distinct TNF receptors, p55 type 1 receptor (TNFR1) and p75 type 2 receptor
      (TNFR2). To determine the role of TNF-alpha in the induction of inflammatory
      responses in the skin, gene-targeted mutant mice lacking either TNFR1 or TNFR2
      were painted with irritant chemicals. Both phenol and croton oil painting onto
      the ears induced less inflammation in TNFR1(-) mice than normal and TNFR2(-)
      mice. Intradermal injection of TNF-alpha (0.2-200 ng for 3 days) into the ear
      induced less inflammation in TNFR1(-) mice than in normal mice. TNFR2(-) mice
      developed a normal inflammatory reaction to high doses of TNF-alpha (20-200 ng
      for 3 days), while they showed minimal reactivity to low doses of TNF-alpha (0.2
      2 ng for 3 days). TNF-alpha is known to trigger the release of a series of other
      cytokines and to induce the expression of cell adhesion molecules, thus
      contributing to the development of inflammation. The levels of protein and mRNA
      for interleukin (IL)-6 were elevated in keratinocytes from normal as well as
      TNFR2(-) mice after treatment with TNF-alpha, while keratinocytes from TNFR1(-)
      mice did not show any up-regulation of IL-6. TNF-alpha induced intercellular
      adhesion molecule (ICAM)-1 expression in the keratinocytes from normal and TNFR2(
      ) mice, but not in those from TNFR1(-) mice. These results indicate that TNFR1 is
      critical for induction of skin inflammation by TNF-alpha.

PMID- 9247583
TI  - Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in
      experimental cerebral malaria.
AB  - Tumor necrosis factor (TNF) has been implicated in the pathogenesis of
      experimental cerebral malaria (CM), but the respective role of its two types of
      receptors has not been established. A significant increase in the expression of
      TNF-receptor 2 (TNFR2, p75), but not of TNFR1 (p55), was found on brain
      microvessels at the time of CM in susceptible animals. Moreover, mice genetically
      deficient for TNFR2 (Tnfr2null) were significantly protected from experimental
      CM, in contrast to TNFR1-deficient (Tnfr1null) mice, which were as susceptible as
      wild-type mice. To identify the factors involved in the protection from CM
      conferred by the lack of TNFR2, we assessed in both knockout and control mice the
      serum concentrations of mediators that are critical for the development of CM, as
      well as the up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the
      brain microvessels. No significant difference in serum levels of TNF and
      interferon-gamma was found between infected wild-type and Tnfr1null or Tnfr2null
      mice. Interestingly, the pronounced ICAM-1 up-regulation and leukocyte
      sequestration, typically occurring in brain microvessels of CM-susceptible
      animals, was detected in infected control and Tnfr1null mice-both of which
      developed CM-whereas no such ICAM-1 up-regulation or leukocyte sequestration was
      observed in Tnfr2null mice, which were protected from CM. Making use of
      microvascular endothelium cells (MVEC) isolated from wild-type, Tnfr1null or
      Tnfr2null mice, we show that soluble TNF requires the presence of both TNF
      receptors, whereas membrane-bound TNF only needs TNFR2 for TNF-mediated ICAM-1 up
      regulation in brain MVEC. Thus, only in MVEC lacking TNFR2, neither membrane
      bound nor soluble TNF cause the up-regulation of ICAM-1 in vitro. In conclusion,
      these results indicate that the interaction between membrane TNF and TNFR2 is
      crucial in the development of this neurological syndrome.

PMID- 9247584
TI  - Cross-reactive memory T cells for Epstein-Barr virus augment the alloresponse to
      common human leukocyte antigens: degenerate recognition of major
      histocompatibility complex-bound peptide by T cells and its role in
      alloreactivity.
AB  - In the present report, cytotoxic T lymphocyte (CTL) clones are described that
      display dual specificity for one of two common human leukocyte antigens (HLA B14
      or B35) as alloantigens, and an immunodominant epitope (FLRGRAYGL) from Epstein
      Barr virus (EBV) that binds to HLA B8. These T cell clonotypes were isolated from
      several unrelated HLA B8+, EBV-exposed individuals, and each distinct cross
      reactivity pattern was associated with a common, public T cell receptor (TCR). In
      some individuals, CTL cross-reactive with these alloantigens completely dominated
      the memory response to this EBV epitope. Moreover, these memory T cells to EBV
      could be reactivated as a significant component of the repertoire of CTL
      responding to allogeneic stimulator cells expressing either HLA B14 or B35. These
      data illustrate how a history of infection with an immunogenic virus such as EBV
      can augment responsiveness to particular alloantigens; such influences may
      underlie the observed clinical association between herpesvirus infection and both
      allograft rejection and graft-versus-host disease. We have also explored the
      molecular basis for T cell cross-reactivity with alloantigens using the HLA B35
      allo-reactive CTL clonotype. To elucidate the structural features of peptides
      that may be cross-recognized by these T cells, mono-substituted analogs of the
      viral epitope were screened for recognition, revealing broad specificity for
      major histocompatibility complex (MHC)-bound peptide. Based on the particular
      amino acid changes tolerated by the CTL at each peptide position, the human
      protein sequence database was searched for possible sequences that were
      recognized in association with HLA B35. Four peptides were identified (MPEATVYGL,
      IPIAPVYGM, KPSPPYFGL, and KPIVVLHGY) that were powerful activating ligands for
      the CTL when presented on HLA B35 but not B8. Thus, equivalent epitopes, capable
      of fully activating a single TCR, were formed by peptides with minimal obvious
      sequence homology bound to either HLA B8 or B35. These data indicate that
      degenerate peptide recognition by TCR may play an important role in the vigorous
      response of self-MHC-restricted T cells to alloantigens.

PMID- 9247585
TI  - Maternal immunoglobulins have no effect on the rate of maturation of the B cell
      compartment of the offspring.
AB  - To elucidate a general role of maternal immunoglobulins (Ig) on the kinetics of B
      cell development of the offspring, we studied non-genetic influences of maternal
      Ig on the developing immune system of B cell-competent mice. These animals were
      the offsprings of either B cell-deprived microMT or of normal C57BL/6 females. In
      these mice, we have compared the kinetics of Ig production, the numbers of B cell
      progenitors, the expression of surface markers specific of the B lineage and the
      progression of Ig variable gene expression. We show that the absence of maternal
      Ig has no detectable effect on the kinetics of IgM and IgG production by the
      offspring's immune system. The number of B cell precursors, the kinetics of
      generation of B cells and their pattern of surface markers expression is
      identical in both types of mice. The acquisition of diversity in the B cell
      repertoire and the changes in the ratios of variable gene family expression are
      also indistinguishable. We conclude that maternally derived Ig has no influence
      on the rate of development and maturation of the B cell compartment of the
      offspring.

PMID- 9247586
TI  - Predominant pathogenic role of tumor necrosis factor in experimental colitis in
      mice.
AB  - Antibodies to tumor necrosis factor (TNF)-alpha have been recently proposed as
      effective treatment for patients with Crohn's disease. Here, we analyze the
      functional role of TNF-alpha in a mouse model of chronic intestinal inflammation
      induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that
      mimics some characteristics of Crohn's disease in humans. Macrophage-enriched
      lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis
      produced 10-30-fold higher levels of TNF-alpha mRNA and protein than cells from
      control mice. When mice with chronic colitis were treated by intraperitoneal
      injection of antibodies to TNF-alpha, an improvement of both the clinical and
      histopathologic signs of disease was found. Isolated macrophage-enriched LP cells
      from anti-TNF-alpha-treated mice produced strikingly less pro-inflammatory
      cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant
      role of TNF-alpha in the mouse TNBS-induced colitis model was further underlined
      by the finding that striking colonic inflammation and lethal pancolitis was
      induced in TNF-alpha-transgenic mice upon TNBS treatment. Conversely, no
      significant TNBS-induced colitis could be induced in mice in which the TNF-alpha
      gene had been inactivated by homologous recombination. Complementation of TNF
      alpha function in TNF-/- mice by the expression of a mouse TNF-alpha transgene
      was sufficient to reverse this effect. Taken together, the data provide direct
      evidence for a predominant role of TNF-alpha in a mouse model of chronic
      intestinal inflammation and encourage further clinical trials with antibodies to
      TNF-alpha for the treatment of patients with Crohn's disease.

PMID- 9247587
TI  - Different cytokine profile and antigen-specificity repertoire in Helicobacter
      pylori-specific T cell clones from the antrum of chronic gastritis patients with
      or without peptic ulcer.
AB  - Helicobacter pylori (Hp) infection almost invariably results in chronic antral
      gastritis, but only a proportion of patients develop peptic ulcer. Some Hp
      strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may
      also depend on the type of the host immune response. In this study, the antigen
      specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived
      from the antral mucosa of five patients with Hp-induced uncomplicated chronic
      gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T
      cell clones derived from six Hp-infected patients with chronic gastritis and
      peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell
      clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34
      clones were specific for cytotoxin-associated protein (CagA). In contrast, 34
      (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were
      able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a
      polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients
      recognized Hp antigens other than CagA, since 13/53 (25%) were specific for
      urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp
      antigens. Results provide evidence that the type of T helper cell response
      against Hp may vary according to the antigen involved and suggest that a
      polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a
      local Th0 response, including interleukin-4 production, may represent an
      individual host factor which contributes to lower the degree of gastric
      inflammation and prevent ulcer complication.

PMID- 9247588
TI  - CD5- CD8 alpha beta intestinal intraepithelial lymphocytes (IEL) are induced to
      express CD5 upon antigen-specific activation: CD5- and CD5+ CD8 alpha beta IEL do
      not represent separate T cell lineages.
AB  - We followed alpha beta T cell receptor (TCR) usage in subsets of gut
      intraepithelial lymphocytes (IEL) in major histocompatibility complex class I
      restricted alpha beta TCR-transgenic (tg) mice. The proportion of tg alpha beta
      TCR+ CD8 alpha beta IEL is reduced compared with CD8+ splenocytes of the same
      animal, particularly under conventional conditions of maintenance. Further
      fractionation of CD8 alpha beta IEL according to the expression level of surface
      CD5 revealed that in conventionally housed animals tg TCR+ CD5- CD8 alpha beta
      IEL are as frequent as in specific pathogen-free (SPF) mice, whereas tg TCR+
      CD5int or, even more pronounced, tg TCR+ CD5hi CD8 alpha beta IEL are greatly
      diminished when compared with mice kept under SPF conditions. Upon antigen
      specific stimulation of CD5- CD8 alpha beta IEL in vitro, CD5 surface expression
      is up-regulated on a large fraction of cells within 48 h. Up-regulation of CD5
      surface expression is further enhanced by the presence of the anti-alpha IEL
      monoclonal antibody 2E7. This clearly demonstrates that CD5-, and CD5+ CD8 alpha
      beta IEL cannot be considered as separate T cell lineages.

PMID- 9247589
TI  - Mouse macrophage development in the absence of the common gamma chain: defining
      receptor complexes responsible for IL-4 and IL-13 signaling.
AB  - The common gamma chain (gamma c) forms a critical component of the receptors for
      interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed gamma c-deficient
      mice to define a role for gamma c signaling in the development and function of
      the macrophage lineage. No major differences in absolute cell numbers, cell
      surface phenotype, or in vitro function of gamma c- compared to gamma c+
      macrophages were observed. We therefore conclude that signaling through the gamma
      c chain is not essential for the differentiation of mouse macrophages. Although B
      and T cells require gamma c for IL-4 responses, IL-4 up-regulated major
      histocompatibility class II molecules and inhibited nitric oxide production from
      gamma c- macrophages following stimulation with lipopolysaccharide and interferon
      gamma. gamma c- macrophages could also respond to IL-13, consistent with the
      model of a type II IL-4 receptor alpha/IL-13R which can function in the absence
      of gamma c. Both IL-4 and IL-13 responses could be completely inhibited with the
      mouse IL-4 antagonist OY, suggesting that all of the observed IL-13 responses
      pass through the type II receptor, making it the primary signaling receptor
      complex for IL-13 in mouse macrophages.

PMID- 9247590
TI  - Agonist-induced T cell receptor down-regulation: molecular requirements and
      dissociation from T cell activation.
AB  - T cell receptor (TCR) down-regulation is a consequence of specific receptor
      engagement and plays an important role in modulating the T cell response. We have
      investigated the role of protein kinase C (PKC) and protein tyrosine kinases
      (PTK) in the induction of TCR down-regulation. We report that the mutation of
      S126 in the CD3-gamma chain that is known to inhibit phorbol-12-myristate 13
      acetate-induced TCR down-regulation does not affect down-regulation induced by a
      specific agonist. In addition, agonist-induced TCR down-regulation is not
      affected by blockade or depletion of PKC, neither by blockade or lack of PTK,
      while the same treatments efficiently interfere with T cell activation. These
      results demonstrate that TCR down-regulation is induced by early events which
      follow specific engagement by an agonist and can be dissociated from those
      required for full T cell activation.

PMID- 9247591
TI  - Single-cell analyses of CD4+ T cells from alpha beta T cell receptor-transgenic
      mice: a distinct mucosal cytokine phenotype in the absence of transgene-specific
      antigen.
AB  - Development of distinct CD4+ T cell cytokine phenotypes may be conditioned by the
      anatomic site in which activation occurs. A double-label in situ hybridization
      technique was used to characterize co-expression of cytokine mRNA in antigen
      specific responses of Peyer's patch (PP), lamina propria (LP), and splenic (SP)
      CD4+ T cells isolated from alpha beta T cell receptor-transgenic mice.
      Interleukin (IL)-2 was the dominant cytokine expressed by antigen-stimulated PP
      and SP populations, though it was expressed by a minority of the activated T
      cells. Cells that expressed interferon (IFN)-gamma were less frequent, and IL-4,
      IL-5, and IL-10 were infrequent. In contrast, cells that expressed IFN-gamma or
      IL-10 were most frequent in the LP population, with lower frequencies of IL-2,
      and few IL-4- and IL-5-positive cells. Co-expression of two cytokines by the same
      cell was the exception, regardless of the anatomic site from which the T cells
      were isolated. The surface phenotype of transgene-positive T cells isolated from
      each anatomic site was distinct, despite the absence of in vivo exposure to
      antigen for which the transgenic T cell receptor is specific. These data suggest
      that the cytokine responses of CD4+ T cells may be conditioned by the
      microenvironment, independently of specific antigen, and that the LP CD4+ T
      population has a distinct cytokine expression pattern with counter-regulatory
      properties that may be important for homeostasis in mucosal immune tissues.

PMID- 9247592
TI  - Impaired induction of cytotoxic T lymphocytes by antagonism of a weak agonist
      borne by a variant hepatitis C virus epitope.
AB  - An epitope that acted as a weak agonist in the cytotoxicity assay was identified
      as part of the capsid protein of a hepatitis C virus (HCV) variant. In a low
      concentration, the variant epitope also had a weak antagonistic effect. When a
      minute amount of this variant epitope was added to the culture for induction, it
      selectively attenuated the expansion of major cytotoxic T cell populations and
      drastically reduced the cytotoxic responses against the wild-type epitope. Thus,
      antagonism to induction suppressed immune responses against both the wild type
      and the variant, thereby helping the persistence of not only variant itself but
      also the wild-type HCV. Because this variant was a weak agonist, most cytotoxic T
      cells induced with the wild-type epitope were cross-reactive with the variant and
      susceptible to the antagonism to induction. Only the T cells which were not cross
      reactive with the variant and not susceptible to the antagonism survived the
      antagonism in induction. This implied that the specificity of the remaining
      immune response, if any, was directed exclusively to the wild-type epitope after
      the emergence of the variant. For viruses like HCV, being heterogeneous itself
      may contribute significantly toward persistent infection through antagonism to
      induction.

PMID- 9247593
TI  - The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell
      precursors via the chemokine receptor CXCR4.
AB  - In the bone marrow, progenitor (pro-) and precursor (pre-) B cells depend on
      close contact with stromal cells for growth and maturation. Stromal cell-derived
      factor 1 (SDF-1), also known as pre-B cell growth-stimulating factor, is produced
      by bone marrow stromal cells and was reported to act together with interleukin-7
      as co-mitogen for pre-B cells. SDF-1 was recently shown to be a chemokine which
      is chemotactic for different types of leukocytes and acts via the chemokine
      receptor CXCR4. Using sorted B220+ bone marrow cells and several B cell lines
      characteristic for different stages of B lymphopoiesis, we now show that SDF-1 is
      a potent attractant for pro- and pre-B cells, but is inactive on B cells at later
      stages of development. In early B cell precursors, SDF-1 induced intracellular
      Ca2+ mobilization and in vitro migration with a potency and efficacy similar to
      that observed for chemokines acting on blood leukocytes. These responses were
      mediated via CXCR4 as they could be inhibited by an antireceptor antibody. SDF-1
      is the first chemokine shown to act on early-stage B cell precursors. Mice
      lacking SDF-1 die perinatally and show a severe deficiency in B lymphopoiesis. We
      propose that SDF-1 released from the stromal cells exerts its critical
      hematopoietic function by selectively attracting and confining early B cell
      precursors within the bone marrow microenvironment that provides the necessary
      factors for growth and differentiation.

PMID- 9247594
TI  - Organ-selective regulation of vascular adhesion protein-1 expression in man.
AB  - Vascular adhesion protein-1 (VAP-1) is an endothelial molecule which mediates
      lymphocyte binding to endothelium in peripheral lymph nodes and at certain sites
      of inflammation. The expression of VAP-1 in vivo is strongly up-regulated in
      inflamed tissues, such as gut and skin. The purpose of this work was to examine
      the factors responsible for this induction of VAP-1. Since the expression of VAP
      1 could not be induced in cultured endothelial cells with a large panel of
      mediators, we used an organ culture technique for the investigation of the
      regulation of VAP-1 expression in a more physiological micromilieu. Indeed, we
      found that the expression of endothelial VAP-1 could be up-regulated in human
      tonsillar tissue with interleukin (IL)-1, IL-4, tumor necrosis factor (TNF
      alpha), interferon (IFN)-gamma and lipopolysaccharide, whereas histamine,
      thrombin, dibutyryl cAMP, N-formyl-Met-Leu-Phe (fMLP) and phorbol 12-myristate 13
      acetate (PMA) had no effect. The induced VAP-1 protein was similar in molecular
      weight to the non-induced VAP-1, suggesting that VAP-1 synthesized de novo
      carries appropriate carbohydrate moieties. In contrast to tonsil organ culture,
      similar inductions performed with human appendix showed no up-regulation of VAP-1
      expression, indicating that the regulation of VAP-1 expression exhibits organ
      selective characteristics. Furthermore, in these tissues the smooth muscle cells,
      which constitutively express VAP-1, could not be stimulated to alter their level
      of expression of this molecule. In conclusion, the expression of VAP-1 can be
      markedly up-regulated with several mediators in tonsil but not in appendix organ
      culture, whereas cultured endothelial cells cannot be induced to express VAP-1.
      These results indicate that the expression of VAP-1 is regulated in a tissue- and
      cell type-selective manner, and a correct micromilieu is required for the up
      regulation to occur.

PMID- 9247596
TI  - An example of idiotypic mimicry.
AB  - We have evaluated the impact of transgenic immunoglobulin (TGIg) expression on
      endogenous antibody repertoires. The transgenic system was chosen as to allow for
      normal recombination of endogenous Ig genes, secretion of TGIg from early
      development on, and distinguishing the TGIg from endogenous Ig by several
      serological markers on the C and V regions of the molecules. The transgenic
      construct encodes a complete anti-(4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NP)
      antibody molecule carrying a well-defined idiotype, bearing a lambda 1 light
      chain and a chimeric heavy chain encoded by a human alpha 2 C region devoid of
      its membrane exon, and the murine B1.8 VDJ-region. Endogenous antibody
      repertoires were analyzed in mitogen-driven limiting dilution cultures, in single
      cell assays for naturally activated Ig-secreting cells, and in hybridomas derived
      by direct fusion of spleen cells from unmanipulated animals. The results show
      that a very high frequency of splenic resting B cells and plasma cells in
      transgenic animals produce IgM with B1.8-cross-reactive idiotypes. This was
      confirmed by hybridoma analysis which also established that the levels of
      transgene expression and of idiotype-positive IgM production by the same cell are
      not correlated. The affinities of idiotype-positive endogenous Ig varied, but
      were generally several orders of magnitude lower than the transgene-encoded
      idiotype. V regions from idiotype-cross-reactive IgM heavy chains showed marked
      diversity in sequences that were all different from the transgenic B1.8. These
      results are compatible with idiotypic mimicry resulting from intercellular
      selection based on degenerate, whole V region reactivities.

PMID- 9247595
TI  - Independent homeostatic regulation of B cell compartments.
AB  - In the present study we used mice with a developmental arrest of B cell
      production to study the ability of a limited number of normal B cell precursors
      to populate peripheral B cell pools. In chimeras reconstituted with mixtures of
      bone marrow (BM) cells from normal and B cell-deficient donors, we show that the
      rate of BM B cell production is a constant function of the number of BM pre-B
      cells and is not modified by the peripheral B cell pool size, i.e. there is no
      feedback regulation of the central pre-B cell compartment by the number of mature
      B cells. We also show that the physiological number of peripheral B cells
      requires a minimum continuous input of newly formed cells, but is not determined
      by the number of B cell precursors. Chimeras with a threefold reduced rate of BM
      B cell production have normal numbers of peripheral B cells. Parabiosis between
      normal and B cell-deficient mice showed that the BM B cell production of one
      mouse suffices to replenish the B cell pool of three mice. Finally, we show that
      the compartment of activated IgM-secreting B cells is homeostatically autonomous
      since the number of cells it comprises is regulated independently of the size of
      the mature B cell pool. The results presented here support a model of the immune
      system in which the size of the different B cell compartments, i.e. pre-B,
      resting B and IgM-secreting, is autonomously regulated.

PMID- 9247597
TI  - Induction of interleukin-2 unresponsiveness and down-regulation of the JAK-STAT
      system upon activation through the T cell receptor.
AB  - Full activation of T cells with antigen (Ag) and antigen-presenting cells
      initiates effector functions and proliferation. When T cells are re-stimulated
      through the T cell receptor (TCR) after a primary stimulation with Ag, growth
      arrest and cell death are induced. Activation of a T cell clone by cross-linking
      of TCR induces interleukin (IL)-2 unresponsiveness and ultimately cell death.
      While the proliferative signal delivered by IL-2 induces c-myc, bcl-2 and cyclin
      D3 expression, the expression of bcl-2 and cyclin D3 is completely suppressed
      upon TCR stimulation. Furthermore, TCR stimulation induces a decrease in the
      protein levels of JAK3 and STAT5, suggesting that IL-2 unresponsiveness and
      growth arrest of T cells result from down-regulation of JAK3 and STAT5.

PMID- 9247598
TI  - Molecular cloning of human RP105.
AB  - RP105 is a 105-kDa type I membrane protein of the leucine-rich repeat (LRR)
      family. Anti-RP105 sensitizes B cells to antigen-receptor-mediated apoptosis, but
      protects B cells from radiation-induced apoptosis and stimulates B cell
      proliferation. The sequence of the mouse RP105 has been reported. Here, we report
      the characterization of the human RP105. The 2.6-kb cDNA encodes a protein of 661
      amino acids which displays 78% homology with mouse RP105. The 22 LRR and the 9
      potential N-linked glycosylation sites within the extracellular region are
      conserved. While previous studies have shown that RP105 is expressed on surface
      IgM+IgD+2 B cells in mice, human RP105 was shown to be expressed on all subsets
      of mature B cells and dendritic cells. Human RP105 gene was mapped to the long
      arm of chromosome 5, where numerous cytokines and receptors have been localized.

PMID- 9247599
TI  - S-methylcysteine and cysteine are inhibitors of induction of glutathione S
      transferase placental form-positive foci during initiation and promotion phases
      of rat hepatocarcinogenesis.
AB  - S-Methylcysteine (SMC) occurs in a variety of plants, including Allium sativum,
      Phaseolus vulgaris, and Cruciferae. In this study, we synthesized five
      organosulfur compounds (OSCs), SMC and four analogs, and examined their modifying
      effects on diethylnitrosamine-induced neoplasia of the liver in male F344 rats,
      using the medium-term bioassay system of Ito (Ito test) based on the two-step
      model of hepatocarcinogenesis. In addition, we investigated the modifying effects
      of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis.
      Carcinogenic potential was scored by comparing the numbers and areas of induced
      glutathione S-transferase placental form (GST-P)-positive hepatocellular focl.
      All OSCs examined had a tendency to decrease the number of GST-P-positive foci
      when given in the promotion stage of the Ito test, and in particular SMC and
      cysteine exerted significant inhibitory effects. When given during the initiation
      stage, these two OSCs also significantly inhibited focus formation. Regarding the
      mechanism underlying the inhibitory effects of SMC and cysteine, measurement of
      ornithine decarboxylase in SMC- and cysteine-treated liver tissues after partial
      hepatectomy (PH) revealed a significantly reduced activity, and the proportion of
      hepatocytes positive for proliferating cell nuclear antigen was significantly
      decreased by SMC or cysteine administration. Moreover, examination of the
      expression of the early response proto-oncogenes, c-fos, c-jun, and c-myc, after
      PH demonstrated down-regulated induction of c-jun mRNA transcripts by SMC,
      sustained for an eight-hour period. Our results support the view that SMC and
      cysteine are chemopreventive agents for rat hepatocarcinogenesis and that their
      intake may be importance for cancer prevention.

PMID- 9247600
TI  - Auraptene, a citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate
      induced tumor promotion in ICR mouse skin, possibly through suppression of
      superoxide generation in leukocytes.
AB  - Coumarin-related compounds, auraptene and umbelliferone, have been isolated from
      the cold-pressed oil of natsumikan (Citrus natsudaidai HAYATA), and tested as
      inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      Epstein-Barr virus activation in Raji cells. The 50% inhibitory concentration
      (IC50) of auraptene (18 microM) was almost equal to that of genistein.
      Umbelliferone, which lacks a geranyloxyl group present in auraptene, was less
      active (IC50 = 450 microM). In a two-stage carcinogenesis experiment with 7,12
      dimethylbenz[a] anthracene (topical application at 0.19 mumol) and TPA (topical
      application at 1.6 nmol) in ICR mouse skin, topical application of auraptene (at
      160 nmol) significantly reduced tumor incidence and the numbers of tumors per
      mouse by 27% (P < 0.01) and 23% (P < 0.05), respectively. Auraptene at a
      concentration of 50 microM markedly suppressed superoxide (O2-) generation
      induced by 100 microM TPA in differentiated human promyelocytic HL-60 cells.
      Having no O2(-)-scavenging potential, auraptene may inhibit the multicomponent
      NADPH oxidase system. Inhibition of intracellular hydroperoxide formation in
      differentiated HL-60 cells by auraptene was also confirmed by flow-cytometric
      analysis using 2',7'-dichlorofluorescein diacetate as a fluorescence probe.
      Quantitative analyses using high-performance liquid chromatography showed the
      occurrence of auraptene not only in both the peels and sarcocarps of natsumikan,
      but also in those of hassaku orange (C. hassaku) and grapefruit (C. paradisi),
      and even in their bottled fresh juice form. These results indicate that auraptene
      is a chemopreventer of skin tumorigenesis, and implies that suppression of
      leukocyte activation might be the mechanism through which it inhibits tumor
      promotion.

PMID- 9247602
TI  - Comparative study on germ cell mutation induced by urethane (ethyl carbamate) gas
      and X-rays in Drosophila melanogaster.
AB  - Although its mutagenicity has not been confirmed in mouse germ cells, urethane
      (ethyl carbamate) gas induces a significant increase of X-linked recessive lethal
      mutations in the germ cells of Drosophila melanogaster. The mutation frequency
      increased as the exposure time was changed from 3.5 to 5.5 h. Mutations were also
      induced by X-rays (20 to 40 Gy) and N-methyl-N-nitrosourea (MNU) (0.06 to 0.10%).
      However, no significant increase of chromosomal changes (partial loss of the Y
      chromosome, total loss of X or Y, and translocations) was produced by urethane,
      although these were readily induced by X-rays. There were large and significant
      increase in chromosomal changes caused by X-rays (20 Gy) compared to urethane
      (5.5 h) or MNU (0.06%). In contrast, there were no substantial differences among
      these three treatments as regards recessive lethal mutations. Urethane-induced
      DNA lesions detected as recessive lethals appear to be intragenic mutations.
      Complementation analysis with 15 reference single-site loci (cistrons) in the
      zeste-white region of the X chromosome revealed that 29 of 723 urethane-induced
      recessive lethals were located in the zeste-white region and all were restricted
      to a single locus. However, among 28 of 890 X-ray-induced lethals, 2 were non
      complementary to 2 or 3 adjacent loci, indicating deletions encompassing 2 or 3
      loci. In addition, 3 of these lethal chromosomes included mutations outside the
      zeste-white region. Another difference between urethane and X-rays was in the
      distribution of mutation sites. Urethane-induced mutations were strikingly non
      random with two hot spots at zw-1 and zw-2, whereas the distribution of X-ray
      induced mutations was more nearly random.

PMID- 9247601
TI  - Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal
      damage in mice treated with ferric nitrilotriacetate.
AB  - The protective effect of alpha G-Rutin against ferric nitrilotriacetate (Fe-NTA)
      induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid
      peroxidation, leading to a high incidence of renal cell carcinoma in rodents.
      Administration of alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation 30
      min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal
      lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg Fe/kg/day for the
      first 3 days and 3 mg Fe /kg/day for 12 days, 5 days a week) causes subacute
      nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal
      tubules. A protective effect was observed in mice given alpha G-Rutin 30 min
      after each Fe-NTA treatment. To elucidate the mechanism of protection by alpha G
      Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of alpha G
      Rutin were investigated by HPLC analysis and by electron spin resonance (ESR)
      spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively. When
      mice were given alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation, rapid
      absorption into the circulation was observed. The plasma concentration of alpha G
      Rutin reached the highest level 30 min after oral administration and then
      decreased to the control level within 60 min, alpha G-Rutin inhibited the
      formation of DMPO-OH in a concentration-dependent manner. Further, chelating
      activity of alpha G-Rutin to ferric ions was shown by spectrophotometric
      analysis. These results suggest that absorbed alpha G-Rutin works as an
      antioxidant in vivo either by scavenging reactive oxygen species or by chelating
      ferric ions and this serves to prevent oxidative renal damage in mice treated
      with Fe-NTA.

PMID- 9247603
TI  - Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in
      human gastric intestinal-type carcinomas in vivo.
AB  - To examine in vivo the validity of the results of experiments in vitro, we
      analyzed the relationship between p53 gene status and apoptotic cell death of
      human gastric intestinal-type adenocarcinomas. Surgical specimens were classified
      into two categories: 18 gastric cancers with nuclear p53 protein (A), and 17
      gastric cancers without nuclear p53 protein (B). Polymerase chain reaction-single
      strand conformation polymorphism disclosed a shifted band that corresponded to a
      mutation in the p53 gene in 13 cases (72%) in category A and 3 cases (18%) in
      category B, the frequency being significantly higher in the former (P < 0.05).
      Apoptotic cells were identified from routinely stained sections and by terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The
      TUNEL index [TI; (the number of TUNEL-positive apoptotic cells/the total number
      of tumor cells) x 100] was 3.8 +/- 1.4% in category A and 4.9 +/- 1.2% in
      category B, the value being significantly lower in the former (P < 0.05). The
      proliferating cell nuclear antigen index, defined similarly to the TI, was 56.4
      +/- 16.3% in category A, and it was significantly higher than that in category B
      (P < 0.05). The immunohistochemically detected expression of p21CIP1/WAP1 did not
      differ between the two categories, while Bax-positive tumor cells were more
      frequently detected in category A. These results indicate that (1) expression of
      a mutated p53 gene attenuates apoptotic cell death of gastric cancer, in
      accordance with the previous in vitro finding that p53 gene mutation provides a
      possible selective advantage for tumor cell proliferation, and (2) apoptosis is
      related not only to expression of p53 and the stage of the cell cycle, but also
      to p53-independent and cell cycle-independent events.

PMID- 9247604
TI  - Comparison of DNA copy numbers in original oral squamous cell carcinomas and
      corresponding cell lines by comparative genomic hybridization.
AB  - We analyzed regional DNA copy numbers in 4 oral squamous cell carcinomas (SCCs)
      by using comparative genomic hybridization, and compared them with those in cell
      lines derived from the SCCs. In the original tumors, DNA copy number increases
      were observed on chromosomes 5p (4/4 cases), 8q (4/4), 20p (3/4), 3q (2/4), 5q
      (2/4), 7p (2/4), 7q (2/4), 11p (2/4), 11q (2/4) and 13q (2/ 4). Although most of
      these changes have been described previously for SCC tumors in the head and neck,
      the incidence of increases in 8q and 20p was much higher in the present study;
      this may be important in relation to cell line establishment, since 8q contains e
      myc, which is involved in immortalization. No common chromosomal region with DNA
      copy number decreases was observed, except for 18q (2/4). When the original
      tumors and the cell lines were compared, their profiles were essentially similar
      with one exception. Further, there was no region that commonly changed in the
      cell lines, but not in the original tumors, suggesting that the DNA copy number
      changes observed in the cell lines mostly represent those of the original tumors.

PMID- 9247605
TI  - Regulation of vimentin expression and protease-mediated vimentin degradation
      during differentiation of human monocytic leukemia cells.
AB  - Terminal differentiation of human monocytic leukemia THP-1 cells is induced in
      vitro by 12-O-tetradecanoylphorbol-13-acetate (TPA). We investigated the effects
      of TPA on the expression of vimentin during the differentiation of THP-1 cells at
      both the mRNA and the protein level. On northern blotting analysis, a 2.1 kb
      vimentin mRNA was up-regulated by TPA. On western blotting, small vimentin
      molecules with a molecular mass of approximately 40 kDa were observed in the
      soluble fraction and increased with TPA-induction of cellular differentiation.
      Since larger, including intact, vimentin molecules were detectable at a high TPA
      dose, we assessed the possible existence of protease activity directed against
      vimentin in THP-1 cells. With incubation of the cellular lysates of THP-1 cells,
      the endogenous vimentin became increasingly smaller over time, suggesting the
      presence of a vimentin-degrading protease. Phenylmethylsulfonyl fluoride
      inhibited this apparent protease activity against vimentin, suggesting the enzyme
      involved to be a serine protease. Interestingly, the protease activity was down
      regulated by TPA treatment. TPA-treated THP-1 cells were found to express a
      vimentin-filament network based on immunocytochemical analysis using an anti
      vimentin monoclonal antibody, V9. Taken together, these observations suggest that
      post-translational mechanisms work in cooperation with transcriptional regulation
      to maintain the vimentin-intermediate filament structure in differentiated THP-1
      cells.

PMID- 9247606
TI  - In vivo retrovirus-mediated herpes simplex virus thymidine kinase gene therapy
      approach for adult T cell leukemia in a rat model.
AB  - We have previously demonstrated that human T-lymphotropic virus type I (HTLV-I)
      tax-expressing human T cell lines are selectively eliminated in the presence of
      aciclovir, using a retroviral vector carrying the herpes simplex virus thymidine
      kinase (HSV TK) gene under the control of the long terminal repeat (LTR) of HTLV
      I. Based on these findings in vitro, we investigated whether this system could
      also be effective in vivo, using a rat model. Following infection of the HTLV-I
      transformed and tax-expressing rat T cell line TARS-1 with this retrovirus (LNLTK
      virus), high levels of HSV TK expression were observed and resulted in increased
      susceptibility to ganciclovir (GCV). Tumors were generated by subcutaneous
      injection of TARS-1 in newborn syngeneic WKA/H rats. While the tumors derived
      from infected TARS-1 cells with control virus, as well as uninfected cells,
      continued to grow in all the rats with or without administration of GCV, those
      derived from LNLTK-infected cells exhibited dramatic regression upon GCV
      treatment. These results indicate that the HTLV-I LTR-HSV TK system also causes
      selective elimination of HTLV-I-transformed, tax-expressing T cells in vivo.
      Therefore, our present study may provide a rationale for clinical gene therapy
      against adult T cell leukemia.

PMID- 9247607
TI  - Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma
      cells reduces tumorigenicity in vivo.
AB  - To investigate the immunoregulatory effect of murine interferon-gamma-inducing
      factor (mIGIF), we transfected Lewis lung carcinoma (LLC) cells with a mammalian
      expression vector containing the mIGIF complementary DNA. The culture medium of
      the transfectant cells stimulated interferon-gamma (IFN-gamma) production by
      spleen cells in vitro in the presence of anti-CD3 antibody and markedly
      potentiated the effect of interleukin-12 (IL-12) on IFN-gamma production by
      spleen cells. mIGIF transfectant cells showed reduction of tumorigenicity and
      induction of an in vivo immuno-protective effect against the parental LLC cells.
      To examine the combined effect of systemic administration of recombinant IL-12
      (rIL-12) and local mIGIF on the tumorigenicity, mice were challenged with LLC or
      transfectant cells on day 0, and the tumor-bearing mice were injected with 50 ng
      of rIL-12 intraperitoneally from day 7 to 11. Systemic rIL-12 showed an anti
      tumor effect. However, mIGIF gene expression did not potentiate this effect of
      systemic rIL-12 in vivo.

PMID- 9247608
TI  - Cell-killing efficiency and number of platinum atoms binding to DNA, RNA and
      protein molecules of HeLa cells treated with combinations of trans
      diaminedichloroplatinum(II) and hyperthermia.
AB  - The effect of hyperthermia on the cell-killing efficiency of Pt atoms binding to
      DNA, RNA and protein molecules was examined. HeLa S-3 cells were treated with
      195mPt-radiolabeled trans-diaminedichloro-platinum(II) (TDDP) for 60 min at
      various temperatures, and the relationship between the lethal effect and the
      number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal
      concentration (D0) of TDDP for a 60-min treatment at 0, 25, 37, 40, 42 and 44
      degrees C was 1714, 1016, 302, 179, 125 and 42.5 microM, respectively. (D0 is
      defined as the dose that would give an average of one lethal event per member of
      the population; for further details, see Fig. 1). By using identically treated
      cells, the numbers of Pt-atoms combined with DNA, RNA and protein molecules were
      determined in the subcellular fractions. Thus, the D0's given as the drag
      concentrations were replaced with the number of Pt-atoms combined in each
      fraction. Then, the cell-killing efficiency of the Pt atom was expressed as the
      reciprocal of the number of Pt-atoms combined and was calculated for each
      molecule. The efficiency for DNA was 0.206, 0.273, 0.779, 1.28, 1.77 and 5.14 x
      10(3) nucleotides, respectively, for the conditions described above. It seemed
      that hyperthermia potentially interacted not only with bifunctional, but also
      with monofunctional bonds. Thus, it was concluded that TDDP was markedly less
      cytotoxic than cis-diaminedichloroplatinum (CDDP) at 37 degrees C, but was more
      cytotoxic than CDDP at 44 degrees C.

PMID- 9247609
TI  - Effect of CPT-11 on lipid peroxide level in mouse tissues.
AB  - We examined the effects of CPT-11 on lipid peroxide level and glutathione
      peroxidase (GSHpx) activity as indices of the toxicity of this antitumor agent in
      mouse and rat tissues. After CPT-11 (100 mg/kg, i.p.) administration, the lipid
      peroxide level in the heart increased 1.5 fold (mice) and 1.3 fold (rats) over
      the control levels. GSHpx activity decreased to 64% of the control. In the lung,
      the lipid peroxide level and GSHpx activity increased 2.5 fold and decreased to
      74% after CPT-11 administration, respectively, compared with the control values.
      These results suggested that CPT-11 may cause cardiotoxicity and pulmotoxicity.
      In rat bone marrow, the lipid peroxide level increased on the 2nd day after CPT
      11 injection. We suggest that in both single and combination treatment with CPT
      11, the possibility of side effects should be taken into consideration.

PMID- 9247610
TI  - Pharmacokinetic study of carboplatin given on a 5-day intravenous schedule.
AB  - We investigated whether carboplatin pharmacokinetics is altered when the drug is
      delivered daily over 5 days, compared to a single-day infusion. Carboplatin was
      infused in 11 patients with lung cancer, who were randomly assigned to 2 groups.
      In the first group, the agent was administered on a conventional single-day
      schedule in the first course and then on a 5-day schedule in the second course.
      In the second group, the order was reversed (crossover design). The dose was
      calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min)
      as a substitute for glomerular filtration rate (GFR): carboplatin (mg) =
      AUCx(Ccr+25), where AUC denotes the area under the concentration versus time
      curve (mg ml-1 min). No difference of carboplatin clearance between the single
      day and 5-day schedule was observed (94.8 +/- 19.9 versus 96.1 +/- 29.9 ml/min, P
      = 0.818, paired t test). The formula systematically overestimated the carboplatin
      clearance: the ratio of estimated clearance/ observed clearance ranged from 1.01
      to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that
      the individual dosing strategy based on renal function can be applied with a 5
      day schedule as well as a single-day schedule. Carboplatin is overdosed when Ccr
      is substituted for GFR in Calvert's formula.

PMID- 9247611
TI  - The rate of mitochondrial mutagenesis is faster in mice than humans.
AB  - We have investigated mitochondrial DNA (mtDNA) mutagenesis in the laboratory
      mouse. Using a nested PCR method for quantification, the absolute frequency,
      tissue distribution and rate of increase of mitochondrial deletion mutations was
      determined. Multiple deletions arise in brain, cardiac muscle and kidney tissues:
      deletions occur most frequently at regions of directly repeated mtDNA homology.
      Deletion frequencies rose by 2.5 x 10(5), 6300- and 4000-fold in heart, brain and
      kidney, respectively, between young and old mice. The rates of mtDNA mutation
      accumulation in mouse and human hearts are modeled well by exponential equations,
      with r-values of 0.96 and 0.97, and mutations rose much faster in mouse than
      human mtDNA per unit time. Thus, maintenance of the human mitochondrial genome is
      much better than that of mice, consistent with the higher rate and final extent
      of total DNA repair in humans than mice, that has been observed by others and
      consistent with the predictions of the disposable soma model of aging. A
      comparison of mtDNA mutagenesis from cardiocytes vs. whole heart tissue was
      undertaken. Deletion mutations were observed to be 100-fold lower in DNA prepared
      from isolated cardiocytes than from whole heart homogenates, consistent with a
      model of uneven mtDNA mutation accumulation.

PMID- 9247612
TI  - Chemopreventive effects of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine
      against benzo[a]pyrene.
AB  - The putative antimutagenic/anticarcinogenic organosulfur compound, S-(N,N
      diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC), has been demonstrated to
      inhibit the metabolic activation and the genotoxicity of N-nitrosodiethylamine.
      We have investigated the chemopreventive activity of AC-DDTC against
      benzo[a]pyrene (B[a]P) in the Salmonella typhimurium bacterial mutation assay, in
      the chromosome aberration assay using Chinese hamster lung fibroblast (CHL), and
      in the mouse micronucleus assay in bone marrow cells. In the bacterial mutation
      assay, AC-DDTC produced a concentration dependent decrease in the number of
      mutant colonies induced by B[a]P. The chromosome damaging responses of B[a]P in
      CHL cells were abolished by the treatment of AC-DDTC, approximately to the level
      of the control. In the in vivo mouse bone marrow micronucleus test, pretreatment
      of AC-DDTC 1 h prior to B[a]P reduced the frequency of micronucleated
      polychromatic erythrocytes. The inhibitory effects were statistically significant
      and dose-dependent. Our results demonstrate that AC-DDTC, one of the mixed
      disulfide model compounds of disulfiram, prevents the mutagenic effects of B[a]P.

PMID- 9247613
TI  - Repair of gamma-irradiation-induced DNA single-strand breaks in human bone marrow
      cells: analysis of unfractionated and CD34+ cells using single-cell gel
      electrophoresis.
AB  - Human bone marrow mononuclear cells (BMMNCs) were separated by density gradient
      centrifugation, and a subpopulation of progenitor cells was further isolated
      using anti-CD34-coated magnetic beads. The cells were irradiated with gamma-rays
      (0.93-5.43 Gy) from a 137Cs source. The extent of DNA damage, i.e., single-strand
      breaks (SSBs) and alkali-labile lesions of individual cells, was investigated
      using the alkaline single-cell gel electrophoresis technique. The irradiation
      resulted in a dose-dependent increase in DNA migration, reflecting the number of
      detectable DNA lesions. An approximately similar extent of SSB formation was
      observed in BMMNCs and CD34 + cells. Damage was repaired when the cells were
      incubated at 37 degrees C: a fast initial repair phase was followed by a slower
      rejoining of SSBs in both BMMNC and CD34 + cell populations. A significantly
      longer time was required to repair the lesions caused by 5.43 Gy than those
      caused by 0.93 Gy. In the present work we report, for the first time, the
      induction and repair of DNA SSBs at the level of single human bone marrow cells
      when exposed to ionizing radiation at clinically relevant doses. These data,
      together with our previous results with human blood granulocytes and lymphocytes,
      indicate an approximately similar extent of formation and repair of gamma
      irradiation-induced DNA SSBs in immature and mature human hematopoietic cells.

PMID- 9247614
TI  - Accumulation of genetic alterations in a human hepatoma cell line transfected
      with hepatitis B virus.
AB  - Chromosome and molecular analyses of the hepatitis B virus (HBV)-transfected
      HepG2T14.1 variant of the HepG2 cell line was conducted. In HepG2T14.1 cells
      several genetic alterations such as de novo aberrations of chromosomes 9, 14, 15,
      and 20 were identified that are not present in the parental HepG2 cell line.
      Furthermore, HepG2T14.1 cells showed loss of heterozygosity (LOH) in the q region
      of chromosome 14. The single HBV integration site in HepG2T14.1 cells mapped to
      the 2q35-36 region of one copy of chromosome 2 by fluorescence in situ
      hybridization (FISH). No genetic changes were identified at or near the HBV
      integration site at the level of these analyses. In addition, growth rates in
      vivo and in vitro were dramatically accelerated in HepG2T14.1 cells. These
      results document that a HBV-transfected hepatoma cell line has de novo genetic
      mutations at several sites of the host genome, one HBV integration site in an non
      rearranged chromosome and an altered phenotype. These findings support our
      hypothesis that HBV might play a role in cellular transformation by interfering
      with cellular processes responsible for the stability of the genome.

PMID- 9247615
TI  - Cytochrome P450 hydroxylation of carbon atoms of the alkyl chain of symmetrical N
      nitrosodialkylamines by human liver microsomes.
AB  - A panel of 14 human liver microsomal preparations metabolized at variable rates
      three symmetrical nitrosodialkylamines (N-nitroso-dipropyl, dibutyl and diamyl
      amines, NDPA, NDBA, NDAA) into aldehydes and hydroxynitrosamines. Formation of
      linear aldehydes, convenient probes for alpha-hydroxylation of alkyl chain, and
      production of hydroxy metabolites of NDPA, NDBA and NDAA were simultaneously
      monitored by two specific HPLC detection methods. The longer the alkyl chain, the
      smaller the metabolic rate of the alpha-hydroxylation of the alkyl chain and the
      greater was the metabolic rate of the corresponding (omega-1)-hydroxy metabolite
      formation. Thus, the (omega-1)-hydroxylation of the alkyl chain was the major
      metabolic pathway of NDBA and NDAA in so far as it represented 3.3- and 86-fold
      of the alpha-hydroxylation. The balance between beta- to omega-hydroxylations and
      alpha-hydroxylation of carbon atoms of the alkyl chain depends upon its length
      and also upon the specific P450 isoform(s) involved. The hydroxylation site of
      the alkyl chain by P450 2E1 depends upon its length. For short alkyl chains, the
      main pathway was alpha-hydroxylation while for long alkyl chains, such as pentyl,
      (omega-1)-hydroxylation became the major pathway. The rate of alpha-hydroxylation
      was shown to be correlated with mutagenesis of 5 dialkylnitrosamines, as inferred
      from literature data, while the (omega-1)-hydroxylation was inversely correlated.
      Furthermore, other P450s than P450 2E1, such as P450 3A4 and 2C were shown to be
      involved in the metabolism of nitrosodialkylamines bearing long alkyl chains.

PMID- 9247616
TI  - Mutagenic effects at HPRT locus induced in Chinese hamster ovary cells by thermal
      neutrons with or without boron compound.
AB  - CHO cells were exposed to thermal neutrons and their mutation frequency was
      determined. The Kyoto University Research Reactor (KUR), which has a very low
      level of contamination by gamma-rays and fast neutrons was used as a thermal
      neutron source. Cells were irradiated in the presence or absence of boric acid to
      determine mutation frequency and cell survival. Thermal neutron irradiation was
      2.5 times as mutagenic as gamma-irradiation without boron. In the presence of
      boron, however, thermal neutron irradiation was from 4.2 to 4.5 times as
      mutagenic as gamma-irradiation. When the mutation frequency was plotted against
      the survival fraction, a higher degree of mutagenicity was observed in the
      presence than in the absence of boron. These results suggest that the enhancement
      of thermal neutron-induced mutation with boron is strongly associated with alpha
      particles released by 10B(n, alpha)7 Li reaction.

PMID- 9247617
TI  - Polyamines and their potential to be antimutagens.
AB  - In order to determine the antimutagenic potential of polyamines, modified Ames
      tests were performed. Polyamines spermine, spermidine and putrescine all showed
      antimutagenic potential against EMS-induced reversions. In addition, the
      polyamines spermidine and putrescine showed potential to reduce the number of
      spontaneous revertants in modified Ames tests. Since spermidine and putrescine
      have the potential to reduce spontaneous mutations, we decided to perform DNA
      fidelity assays. DNA fidelity assays confirmed that putrescine has the potential
      to reduce the mutation frequency. However, spermidine had no effect. This
      suggests that putrescine may play a vital role in DNA synthesis and possibly be
      the active compound that plays a role in affecting EMS-induced mutations in the
      modified Ames tests. This is possible since all cells have the potential to
      convert spermine and spermidine to putrescine. However, since the DNA fidelity
      assay is an in vitro assay, the enzymes required for the conversion of spermine
      and spermidine to putrescine are absent. The possibility of conversion and the
      rate of conversion need further study.

PMID- 9247618
TI  - Food-derived heterocyclic amines potentiate the mutagenicity of a drinking water
      mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX).
AB  - We investigated the enhancing effect of heterocyclic amines on base-substitution
      mutations with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-amino
      3,4-dimethyl-imidazo[4,5-f]quinoline (MeIQ). We compared the mutagenicity of 3
      chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the presence and
      absence of the heterocyclic amines in E. coli WP2 (trpE) and in excision repair
      deficient strains WP2s (uvrA, trpE) and ZA500 (uvrA, rfa, trpE). Since the assay
      was performed without microsomal metabolic activation, Trp-P-1 and MeIQ alone
      were not mutagenic. In WP2, trp+ reversions induced by MX were greatly
      potentiated by Trp-P-1 and slightly potentiated by MeIQ. Mutation enhancement was
      not observed in strains WP2s and ZA500, suggesting that a functional DNA excision
      repair system is necessary for the combined action of MX and heterocyclic amines.
      Our finding implies that the combined effect of mutagens as well as the effect of
      individual mutagens, should be considered in risk evaluation.

PMID- 9247619
TI  - Effects of vitamins A and E on methylazoxymethanol-induced mutagenesis in
      Salmonella typhimurium strain TA100.
AB  - The aim of this study is to report the antimutagenic effect of vitamin A and
      vitamin E towards methylazoxymethanol (MAM)-induced mutagenesis in Salmonella
      typhimurium strain TA100 sensitive to alkylating agents. In order to characterize
      different levels of action of these two fat-soluble vitamins towards the
      mutagenicity of MAM, several assays have been considered to show the
      antimutagenic effect and the possible interactions of vitamins with MAM or with
      the bacteria. Thus, for each vitamin, three different assays with three different
      incubations have been conducted: (i) MAM, bacteria and vitamins together, (ii)
      MAM and vitamins, (iii) bacteria and vitamins. The results showed that both
      vitamins A and E present an antimutagenic effect towards MAM induced mutagenesis.
      alpha-Tocopherol seems to have an action directly on to the mutagenic agent,
      whereas the action of retinol is likely due to a protection of the bacterial
      genoma against MAM. These in vitro results could help to interpret results of
      colon carcinogenesis studies using animals induced by 1,2-dimethylhydrazine and
      fed vitamins supplemented diet.

PMID- 9247620
TI  - Oxidative stress-related clastogenic factors in plasma from Chernobyl
      liquidators: protective effects of antioxidant plant phenols, vitamins and
      oligoelements.

PMID- 9247621
TI  - Chromosomal study in lymphocytes from subjects living or working in buildings
      constructed with radioactively contaminated rebar.
AB  - It has recently been found that many buildings in Taiwan were constructed with
      radioactively contaminated rebar, which raised great concern among the residents
      as well as governmental officials. In order to investigate the possible
      cytogenetic damage to the residents of contaminated buildings, a G-banding method
      was carried out on the lymphocytes of 30 radiation-exposed individuals from four
      families and one office building, as well as 15 control individuals from
      laboratory personnel. The estimated cumulative radiation doses for the exposed
      people range from 19.63 to 280.50 mSv. Altogether, 13 females and 17 males
      belonging to the radiation-exposed group, and 7 females and 8 males in the
      control group, were included in this study. With the exception of one sample, at
      least 500 metaphase spreads were scored and analyzed for each individual. All the
      recognizable structural aberrations of chromosomes or chromatids were recorded
      and statistically analyzed. Comparison of either percentage of cells with
      chromosome aberrations or number of aberrated chromosomes per 100 cells between
      the radiation-exposed and the control groups manifested insignificant differences
      (p = 0.1145 and 0.0766, respectively). In addition, the chromosomal regions close
      to the centromere were found to break more frequently than elsewhere in the
      genome.

PMID- 9247622
TI  - Mutational specificity of glyoxal, a product of DNA oxidation, in the lacI gene
      of wild-type Escherichia coli W3110.
AB  - To determine the mutation spectrum of glyoxal, which is produced from DNA by
      oxygen free-radicals, we analyzed the chromosomal lacI gene of mutants induced by
      treatment of a wild-type Escherichia coli strain with glyoxal. The cell death and
      the mutation frequency increased according to the concentration of glyoxal added
      to the culture medium. The majority of the spontaneous mutations (82%) and that
      of the glyoxal-induced mutations (50%) were the addition or deletion of a 5'-TGGC
      3' sequence at positions 623-634, which was reported to be a mutational hot spot
      in the lacI gene. In the glyoxal-induced mutants, however, the ratio of base-pair
      substitutions was increased (35%). Although all types of base-pair substitutions
      were detected, 78% of the base-pair substitutions occurred at G:C sites. Among
      them, G:C-->A:T transitions were predominant, followed by G:C-->T:A
      transversions. These mutations appeared to be distributed randomly within the
      lacI gene. These results suggest that glyoxal-induced mutations may correlate to
      mutations induced by oxygen free-radicals.

PMID- 9247623
TI  - Nebularine (9-2'-deoxy-beta-D-ribofuranosylpurine) has the template
      characteristics of adenine in vivo and in vitro.
AB  - Nebularine (9-beta-D-ribofuranosylpurine; Nb) is a naturally occurring nucleoside
      with structural features suggestive of a universal base. However, previous
      observations based on thermal melting characteristics of oligonucleotides
      suggested that Nb formed stable pairs only with thymine. To determine the
      template characteristics of Nb, we constructed M13 viral single-stranded DNA
      (ssDNA) molecules bearing a single site-specific deoxynebularine (9-2'-deoxy-beta
      D-ribofuranosylpurine) residue. The ssDNA constructs were transfected into
      Escherichia coli cells to determine the specificity of base insertion opposite
      Nb, as well as to determine the effect of Nb on the replicability of the
      transfected DNA. Base insertion opposite Nb, analyzed by a multiplex sequencing
      technology, suggests that Nb has the template characteristics of adenine.
      Analysis of DNA replicability, measured as transfection efficiency, indicates
      that Nb does not block DNA replication. UV irradiation of host cells before
      transfection did not significantly affect survival or base insertion specificity
      within the limits of multiplex sequencing technology employed, suggesting that
      inducible mutagenic phenomena appear to have only minor effects on translesion
      synthesis across Nb. In addition, in vitro DNA elongation experiments on
      oligonucleotide templates using E. coli DNA polymerase I (Klenow fragment) as the
      model polymerase showed that Nb templates for T, but not for other bases under
      the tested conditions. The data reported in this communication underscore the
      importance of base-pair geometry as a specificity-determinant during base
      insertion by replicative polymerases.

PMID- 9247624
TI  - The role of poly(ADP-ribose)polymerase in the induction of sister chromatid
      exchanges and micronuclei by mitomycin C in Down's syndrome cells as compared to
      euploid cells.
AB  - Inhibitors of poly(ADP-ribose)polymerase (PARP; EC 2.4.2.30), such as 3
      aminobenzamide (3-AB), can be used to assess the role of the enzyme in the
      induction of DNA lesions in euploid cells as compared to cells of genetic
      conditions known to exhibit increased susceptibility to chemical or physical
      mutagens, such as Down's syndrome (DS) lymphocytes. We report in this work on the
      effect of PARP inhibition by 3-AB in the induction of sister chromatid exchanges
      (SCE) and micronuclei (MN) in DS lymphocytes as compared to lymphocytes from
      normal controls exposed in vitro to a gradient of mitomycin C (MMC). For both
      types of cells, DS and normal lymphocytes, MMC induces a significant increase in
      frequencies of SCE and MN in the absence and in the presence of 3-AB. In the
      presence of 3-AB the yield of SCE and MN induced by MMC was significantly higher
      in normal lymphocytes as compared to lymphocytes from DS patients. The molecular
      mechanisms by which 3-AB affects the yield of SCE and MN remains to be fully
      elucidated; however, it seems clear that DS patients display a different behavior
      in what concerns poly(ADP-ribosyl)ation as compared to normal individuals.

PMID- 9247625
TI  - DNA effects in repair-deficient V79 Chinese hamster cells studied with the comet
      assay.
AB  - Using the alkaline comet assay (single cell gel electrophoresis), we studied the
      induction and persistence of DNA damage induced by methyl methanesulfonate (MMS)
      and neocarzinostatin (NCS) in the repair-deficient Chinese hamster cell lines V
      E5 and XR-V15B. Effects in the comet assay were analyzed directly after treatment
      as well as after a postincubation period in mutagen-free medium to gain insight
      into the DNA repair capacities of the mutant cell lines in relation to different
      primary DNA lesions. Both mutagens caused a concentration-related increase in DNA
      strand breakage in both mutant cell lines and in the normal parental cell lines.
      Repair of MMS-induced DNA damage during postincubation was similar in normal and
      mutant cell lines, while diminished repair was seen after NCS treatment in XR
      V15B cells. Our data show that XR-V15B cells only repaired about 30% of NCS
      induced DNA damage within 1 h, while the parental V79 cell line repaired about
      70%. Since this cell line is defective in the repair of DNA double-strand breaks
      (DSB), the results indicate that NCS-induced DSB significantly contribute to the
      genotoxic effects seen in the comet assay. However, compared to previously
      studied induction of gene mutations and chromosome aberrations, detection of NCS
      induced DNA effects with the comet assay was less sensitive and increased DNA
      migration only occurred under strong cytotoxic conditions.

PMID- 9247626
TI  - The metalloporphyrin/oxidant model for cytochrome P450.

PMID- 9247627
TI  - The RET proto-oncogene in medullary and papillary thyroid carcinoma. Molecular
      features, pathophysiology and clinical implications.
AB  - The evolution of cancer is a multistep phenomenon, and multiple cellular genetic
      lesions are involved in the emergence of the malignant neoplasm. Several early
      events have been implicated in the neoplastic transformation of thyrocytes, and
      recent reports have described the involvement of specific genetic alterations in
      different types of thyroid neoplasms: ras point mutations are frequently observed
      in tumours with follicular histology, gsp-the mutated form of the alpha subunit
      of the Gs-protein-is encountered in up to 73% of papillary or follicular thyroid
      carcinomas, and a high prevalence of p53 point mutations has been found in
      anaplastic thyroid carcinomas but not in differentiated follicular tumours. More
      recent studies revealed that the RET proto-oncogene is involved in the
      oncogenesis of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma
      (PTC) by activation of its tyrosine kinase either by point mutation or
      rearrangement. In this review the most important recently published data on
      alterations of the RET proto-oncogene in heritable and sporadic MTCs and in PTCs
      will be summarized. Emphasis will be directed to the pathophysiological
      mechanisms of tumour initiation, the indications and limitations of DNA testing,
      and the clinical implications of identified RET defects in thyroid lesions.

PMID- 9247628
TI  - Differing degree and distribution of gastritis in Helicobacter pylori-associated
      diseases.
AB  - Infection with Helicobacter pylori (H. pylori) causes gastritis, and may be
      associated with gastric and duodenal ulcers and also with such malignant diseases
      as MALT lymphoma and gastric carcinoma. In order to determine whether there are
      differences in the degree and distribution of gastritis, each patient with H.
      pylori gastritis only (n = 50) was matched for sex and age with four patients,
      one each with H. pylori-associated duodenal ulcer, gastric ulcer, gastric
      carcinoma or MALT lymphoma. From each patient, two biopsies were taken from the
      antrum and two from the corpus for histopathological examination of H. pylori
      gastritis. The median summed gastritis score decreases in the following order:
      antrum: gastric ulcer > duodenal ulcer > gastritis alone > carcinoma > MALT
      lymphoma, and corpus: gastric ulcer > carcinoma > MALT lymphoma > gastritis alone
      and duodenal ulcer. We conclude that the degree and distribution of H. pylori
      gastritis differs significantly among H. pylori-associated diseases. These
      differences may explain some of the underlying pathomechanisms associated with H.
      pylori infection.

PMID- 9247629
TI  - p53 alterations in thymic epithelial tumours.
AB  - The prognosis of thymic epithelial tumours depends on malignant behaviour that
      cannot always be predicted on histological grounds. This study aimed at
      identifying a molecular marker that would be useful in overcoming the drawbacks
      of histopathology. Forty-four thymic epithelial tumours were analysed for
      alterations of the tumour suppressor gene p53 using immunohistochemistry
      (antibodies D0-1 and CM-1) and PCR-based single-strand conformation polymorphism
      and DNA sequencing. Histological and clinical evaluation and also p53 analysis
      revealed three major tumour groups: non-organotypic thymic carcinomas with
      frequent p53 alterations (7/9) and occurrence of p53 gene mutations (2/9);
      malignant thymomas with frequent p53 alterations but without p53 gene mutations
      (11/18); and benign thymomas with rare p53 alterations and without p53 gene
      mutations (2/17). In non-organotypic thymic carcinomas p53 was detected with both
      antibodies. In contrast, thymomas lacked immunoreaction with D0-1 suggesting
      alteration of the antibody-binding site. Overall immunohistochemical results
      correlated with clinical stages (P < 0.01), pathohistology (P < 0.01), and
      survival times (P < 0.05). We consider immunohistochemical p53 detection to be a
      useful new prognostic factor for the evaluation of thymic epithelial tumours.

PMID- 9247630
TI  - Endocrine cells in intraductal papillary-mucinous neoplasms of the pancreas. A
      histochemical and immunohistochemical study.
AB  - The endocrine cells in intraductal papillary-mucinous neoplasms (IPN) of the
      pancreas have rarely been investigated. In the normal pancreatic ducts of normal
      pancreases (n = 5) there were a few endocrine cells: argyrophil in 5 (100%),
      chromogranin A in (100%), pancreatic polypeptide (PP) in 3 (60%), and insulin in
      7 (20%). These endocrine cells were scattered, and located in the basal portions
      of pancreatic ducts. In IPN of the pancreas (n = 9), there were many endocrine
      cells: argyrophil in 7 (78%), argentaffin in 8 (89%), chromogranin A in 8 (89%),
      PP in 7 (78%), serotonin in 7 (78%), insulin in 4 (44%), and gastrin in 5 (56%).
      In invasive ductal adenocarcinoma of the pancreas (n = 6), many endocrine cells
      were also detected: argyrophil cells in (67%), chromogranin A in 3 (50%), insulin
      in 3 (50%), glucagon in 4 (67%), and somatostatin in 3 (50%). In positive cases,
      endocrine cells were situated under or among the neoplastic cells and the
      proportion of endocrine cells in IPN was less than 5% of the total neoplastic
      cell population. These data show that normal pancreatic ducts contain endocrine
      cells and that IPN frequently contain argyrophil, argentaffin, chromogranin A,
      and hormone-containing endocrine cells. These data also suggest that endocrine
      differentiation occurs during neoplastic transformation and progression of IPN of
      the pancreas.

PMID- 9247631
TI  - Glutathione S-transferase pi-class as a tumour marker in lingual preneoplastic
      and neoplastic lesions of rats and humans.
AB  - Immunocytochemical expression of the pi class glutathione S-transferase (GST) was
      investigated in preneoplastic and neoplastic lingual lesions in a 4-nitro
      quinoline 1-oxide (4NQO)-induced rat genetic model [Wistar/Furth rats (WF) and
      Dark-Agouti rats (DA)] and in human surgical material [fibrous polyp, mild to
      moderate dysplasia, severe dysplasia, carcinoma in situ (CIS), squamous cell
      carcinoma (SCC)]. Two polyclonal antibodies raised against rat (GST-P) and human
      (GST-pi) antigens were used. In the rat model, DA and WF rats showed contrasting
      susceptibility to 4NQO, DA rats having a much higher tumour incidence and a
      significantly shorter survival time than WF rats. While the established lingual
      SCC in DA and WF rats all expressed GST-P, the number of GST-P+ foci in the
      preneoplastic lingual epithelium was significantly higher in DA (14.5 +/- 6.5)
      than in WF rats (5.5 +/- 2.6; P < 0.0001). In contrast, GST-pi epithelial
      staining in human specimens was more variable and the results overlapped in
      different groups. More frequent nuclear and/or basal cell staining was detected
      in severe dysplasia, CIS and SCC than in benign and mild to moderate dysplastic
      lesions. Although the pi class GST may be a useful marker for rat lingual
      carcinogenesis, its value in clinical applications is unclear. GST-pi staining
      patterns and their distribution may be helpful in identifying high-risk lingual
      lesions in humans.

PMID- 9247632
TI  - Establishment of a new continuous clear cell sarcoma cell line. Morphological and
      cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts.
AB  - Clear cell sarcoma (CCS), a rare tumour of deep soft tissues, often has a t(12;
      22) (q13; q12) translocation that induces the formation of a hybrid EWS/ATF-1
      gene. To investigate these alterations further, we established a new continuous
      cell line directly from a CCS taken from a 9-year-old girl. The cultures were
      characterized with respect to morphological, ultrastructural, immunohistochemical
      and karyotypical features and were tested by reverse transcription PCR (RT-PCR)
      for chimaeric EWS/ATF-1 transcripts. The continuous cell line, designated KAO, is
      tumorigenic in nude mice, and the resultant tumours resemble the primary CCS. The
      tumour cells and the cultured cells have melanosomes in their cytoplasm and are
      immunoreactive with the melanoma-specific antibody HMB45, but do not express S
      100 protein. The cultured CCS cells have the t(12; 22)(q13; q12) translocation
      and express the hybrid EWS/ATF-1 gene. No transcripts of the hybrid gene were
      detected in a malignant cutaneous melanoma tested simultaneously. Although CCS
      and malignant melanoma are morphologically related, the present results suggest
      that their geneses differ at the chromosome and molecular levels. They also
      indicate that chromosome analysis and detection of fusion EWS/ATF-1 transcripts
      may be useful adjuvant tools for the diagnosis of CCS.

PMID- 9247633
TI  - Glomerular handling of immune complex in the acute phase of active in situ immune
      complex glomerulonephritis employing cationized ferritin in rats. Ultrastructural
      localization of immune complex, complements and inflammatory cells.
AB  - The ultrastructural localization of immune complex (IC) and inflammatory mediator
      systems in the glomerulus was investigated in active in situ IC
      glomerulonephritis employing cationized ferritin in rats. Glomerulonephritis was
      induced by unilateral renal perfusion of cationized ferritin as antigen (Ag) in
      preimmunized rats, and anti-ferritin antibody (Ab), C3 and the rat C5b-9 complex
      were localized by means of immunogold electron microscopy. Ag-Ab complexes were
      initially formed subendothelially, associated with C3, and attracted platelets,
      polymorphonuclear leucocytes (PMN) and monocytes. Then Ag-Ab complexes, without
      C3, passed across the glomerular basement membrane to re-aggregate
      subepithelially accompanied by C3 deposition after 1 day. Ag-Ab complexes without
      C3 accumulated in the inter-podocyte space within 1 day and were seen in the
      epithelial cells at 6 h. C5b-9 complexes were found in subepithelial immune
      deposits and in membrane vesicles of the epithelial cells, but only in very small
      amounts in subendothelial immune deposits. Accumulated platelets, PMN, and
      monocyte were in direct contact with endothelial cells or subendothelial IC. PMN
      and monocytes contained Ag, Ab and C3 in intracytoplasmic vacuoles. Ag-Ab
      complexes were also found in the mesangial matrix adjacent to the subendothelial
      region after 2 h and increased slightly in number, with expansion of the
      mesangial area thereafter. Most ICs formed in the subendothelial space rapidly
      formed lattices of a size that activated C3 and were then translocated to the
      subepithelial space. The potential ability of C3 to solubilize ICs in the
      subendothelial region may be important in this process. Endocytosis of
      subendothelial ICs by PMN and/or monocytes and the movement of ICs to the
      mesangial matrix may also contribute to the removal of IC from the subendothelial
      space.

PMID- 9247634
TI  - Light and electron microscopic investigation of the process of healing of the
      naevus of Ota by Q-switched alexandrite laser irradiation.
AB  - Melanocytes in the naevus of Ota were destroyed by irradiation using the Q
      switched alexandrite laser. This laser is highly selective and highly absorbed by
      melanosomes. Other cells and tissue components of the dermis remained almost
      intact. Melanosomes were vaporized or fragmented to subelectron microscopical
      size, or degenerated. If the irradiated energy was sufficient, melanocytes
      vanished and large vacuoles several times the size of dermal melanocytes formed
      at the sites. If it was too weak, dermal melanocytes were also vaporized, but
      vacuoles formed within them. Nuclei were no longer discernible. Following
      irradiation macrophages infiltrated the irradiated areas and scavenged
      degenerated melanosomes and cellular debris. Thus, discoloration of the skin was
      markedly reduced. Although a few melanocytes and melanophages remained,
      pigmentation cleared to a satisfactory level. Melanocytes and keratinocytes were
      also injured in the epidermis; however, the epidermis recovered completely. No
      scarring was observed.

PMID- 9247635
TI  - Retroperitoneal bronchogenic cyst masquerading clinically and radiologically as a
      phaeochromocytoma.
AB  - Bronchogenic cysts are relatively rare congenital anomalies that represent
      malformations of the embryonic foregut and are morphologically expressed as
      maldevelopments of the respiratory system. Anatomically, they can be positioned
      at any location along the central axis of the respiratory system, but are more
      commonly discovered in the thorax. Infradiaphragmatic bronchogenic cysts are rare
      and retroperitoneal ones distinctly unusual. We report a retroperitoneal
      bronchogenic cyst clinically masquerading as a phaeochromocytoma.

PMID- 9247636
TI  - E.B. Wilson Award Lecture, 1996. Differential gene action.

PMID- 9247637
TI  - Integrin alpha 6 beta 4 forms a complex with the cytoskeletal protein HD1 and
      induces its redistribution in transfected COS-7 cells.
AB  - The integrin alpha 6 beta 4 is a major component of hemidesmosomes, in which it
      is linked to intermediate filaments. Its presence in these structures is
      dependent on the beta 4 cytoplasmic domain but it is not known whether beta 4
      interacts directly with keratin filaments or by interaction with other proteins.
      In this study, we have investigated the interaction of GST-cyto beta 4A fusion
      proteins with cellular proteins and demonstrate that a fragment of beta 4A,
      consisting of the two pairs of fibronectin type III repeats, separated by the
      connecting segment, forms a specific complex containing a 500-kDa protein that
      comigrates with HD1, a hemidesmosomal plaque protein. A similar protein was also
      bound by a glutathione S-transferase fusion protein containing the cytoplasmic
      domain of a variant beta 4 subunit (beta 4B), in which a stretch of 53 amino
      acids is inserted in the connecting segment. Subsequent immunoblot analysis
      revealed that the 500-kDa protein is in fact HD1. In COS-7 cells, which do not
      express alpha 6 beta 4 or the hemidesmosomal components BP230 and BP180, HD1 is
      associated with the cytoskeleton, but after transfecting the cells with cDNAs for
      human alpha 6 and beta 4, it was, instead, colocalized with alpha 6 beta 4 at the
      basal side of the cells. The organization of the vimentin, keratin, actin, and
      tubulin cytoskeletal networks was not affected by the expression of alpha 6 beta
      4 in COS-7 cells. The localization of HD1 at the basal side of the cells depends
      on the same region of beta 4 that forms a complex containing HD1 in vitro, since
      the expression of alpha 6 with a mutant beta 4 subunit that lacks the four
      fibronectin type III repeats and the connecting segment did not alter the
      distribution of HD1. The results indicate that for association of alpha 6 beta 4
      with HD1, the cytoplasmic domain of beta 4 is essential. We suggest that this
      association may be crucial for hemidesmosome assembly.

PMID- 9247638
TI  - Serine phosphorylation site of the 46-kDa mannose 6-phosphate receptor is
      required for transport to the plasma membrane in Madin-Darby canine kidney and
      mouse fibroblast cells.
AB  - Up to 4% of the human 46-kDa mannose 6-phosphate receptor (MPR46) expressed in
      Madin-Darby canine kidney (MDCK) cells are localized at the cell surface. At
      steady state, the expression of MPR46 on the apical surface of filter-grown MDCK
      cells is about sixfold lower than on the basolateral surface. The cytoplasmic
      domain of the MPR46 is phosphorylated on serine 56 at low stoichiometry. By
      expressing mutant MPR46 we have shown that the MPR46 phosphorylation site is
      required for delivery to the plasma membrane. In addition, mutant MPR46 expressed
      in MPR-deficient mouse embryonic fibroblasts were not detected at the cell
      surface and their ability to sort newly synthesized cathepsin D was not altered.
      Since the loss of MPR46 phosphorylation correlates with the lack of cell surface
      expression, phosphorylation of serine 56 may either function as a direct plasma
      membrane targeting signal or inhibit MPR46 recycling from endosomes to Golgi,
      resulting in trafficking to the cell surface.

PMID- 9247639
TI  - Phosphatidylinositol 3-kinase is not required for recycling of mannose 6
      phosphate receptors from late endosomes to the trans-Golgi network.
AB  - Mannose 6-phosphate receptors carry newly synthesized lysosomal hydrolases from
      the trans-Golgi network to endosomes, then return to the trans-Golgi network for
      another round of enzyme delivery. Wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase, interferes with the delivery of newly synthesized
      lysosomal enzymes to lysosomes. We used two independent assays of mannose 6
      phosphate receptor trafficking to determine the precise step that is blocked by
      wortmannin. Using an assay that monitors resialylation of desialylated cell
      surface 300-kDa mannose 6-phosphate receptors, we found that receptor endocytosis
      and transport to the trans-Golgi network were not inhibited by 2 microM
      wortmannin. In addition, this concentration of drug had no effect on the
      transport of the mannose 6-phosphate receptor from late endosomes to the trans
      Golgi network using a system that reconstitutes this transport process in cell
      extracts. Under the same conditions, wortmannin significantly inhibited the
      generation of mature cathepsin D. In addition, the structurally unrelated
      phosphatidylinositol 3-kinase inhibitor, LY294002, was also without effect when
      added to in vitro endosome-trans-Golgi network transport reactions. These
      experiments demonstrate that the interruption in lysosomal enzyme targeting is
      most likely due to a wortmannin-sensitive process required for the export of
      these receptors from the trans-Golgi network, consistent with the established
      role of phosphatidylinositol 3-kinase in the equivalent transport process in
      Saccharomyces cerevisiae.

PMID- 9247640
TI  - Drosophila PLUTONIUM protein is a specialized cell cycle regulator required at
      the onset of embryogenesis.
AB  - Unfertilized eggs and fertilized embryos from Drosophila mothers mutant for the
      plutonium (plu) gene contain giant polyploid nuclei resulting from unregulated S
      phase. The PLU protein, a 19-kDa ankyrin repeat protein, is present in oocytes
      and early embryos but is not detectable after the completion of the initial rapid
      S-M cycles of the embryo. The persistence of the protein during the early
      embryonic divisions is consistent with a direct role in linking S-phase and M
      phase. When ectopically expressed in the eye disc, PLU did not perturb the cell
      cycle, suggesting that PLU regulates S-phase only in early embryonic development.
      The pan gu (png) and giant nuclei (gnu) genes also affect the S-phase in the
      unfertilized egg and early embryo. We show that functional png is needed for the
      presence of PLU protein. By analyzing png mutations of differing severity, we
      find that the extent of the png mutant phenotype inversely reflects the level of
      PLU protein. Our data suggest that PLU protein is required at the time of egg
      activation and the completion of meiosis.

PMID- 9247641
TI  - Immunoisolation and partial characterization of endothelial plasmalemmal vesicles
      (caveolae).
AB  - Plasmalemmal vesicles (PVs) or caveolae are plasma membrane invaginations and
      associated vesicles of regular size and shape found in most mammalian cell types.
      They are particularly numerous in the continuous endothelium of certain
      microvascular beds (e.g., heart, lung, and muscles) in which they have been
      identified as transcytotic vesicular carriers. Their chemistry and function have
      been extensively studied in the last years by various means, including several
      attempts to isolate them by cell fractionation from different cell types. The
      methods so far used rely on nonspecific physical parameters of the caveolae and
      their membrane (e.g., size-specific gravity and solubility in detergents) which
      do not rule out contamination from other membrane sources, especially the
      plasmalemma proper. We report here a different method for the isolation of PVs
      from plasmalemmal fragments obtained by a silica-coating procedure from the rat
      lung vasculature. The method includes sonication and flotation of a mixed vesicle
      fraction, as the first step, followed by specific immunoisolation of PVs on
      anticaveolin-coated magnetic microspheres, as the second step. The mixed vesicle
      fraction, is thereby resolved into a bound subfraction (B), which consists
      primarily of PVs or caveolae, and a nonbound subfraction (NB) enriched in
      vesicles derived from the plasmalemma proper. The results so far obtained
      indicate that some specific endothelial membrane proteins (e.g., thrombomodulin,
      functional thrombin receptor) are distributed about evenly between the B and NB
      subfractions, whereas others are restricted to the NB subfraction (e.g.,
      angiotensin converting enzyme, podocalyxin). Glycoproteins distribute unevenly
      between the two subfractions and antigens involved in signal transduction [e.g.,
      annexin II, protein kinase C alpha, the G alpha subunits of heterotrimeric G
      proteins (alpha s, alpha q, alpha i2, alpha i3), small GTP-binding proteins,
      endothelial nitric oxide synthase, and nonreceptor protein kinase c-src] are
      concentrated in the NB (plasmalemma proper-enriched) subfraction rather than in
      the caveolae of the B subfraction. Additional work should show whether
      discrepancies between our findings and those already recorded in the literature
      represent inadequate fractionation techniques or are accounted for by chemical
      differentiation of caveolae from one cell type to another.

PMID- 9247642
TI  - The Chlamydomonas Dhc1 gene encodes a dynein heavy chain subunit required for
      assembly of the I1 inner arm complex.
AB  - Multiple members of the dynein heavy chain (Dhc) gene family have been recovered
      in several organisms, but the relationships between these sequences and the Dhc
      isoforms that they encode are largely unknown. To identify Dhc loci and determine
      the specific functions of the individual Dhc isoforms, we have screened a
      collection of motility mutants generated by insertional mutagenesis in
      Chlamydomonas. In this report, we characterize one strain, pf9-3, in which the
      insertion event was accompanied by a deletion of approximately 13 kb of genomic
      DNA within the transcription unit of the Dhc1 gene. Northern blot analysis
      confirms that pf9-3 is a null mutation. Biochemical and structural studies of
      isolated axonemes demonstrate that the pf9-3 mutant fails to assemble the I1
      inner arm complex, a two-headed dynein isoform composed of two Dhcs (1 alpha and
      1 beta) and three intermediate chains. To determine if the Dhc1 gene product
      corresponds to one of the Dhcs of the I1 complex, antibodies were generated
      against a Dhc1-specific peptide sequence. Immunoblot analysis reveals that the
      Dhc1 gene encodes the 1 alpha Dhc subunit. These studies thus, identify the first
      inner arm Dhc locus to be described in any organism and further demonstrate that
      the 1 alpha Dhc subunit plays an essential role in the assembly of the I1 inner
      arm complex.

PMID- 9247644
TI  - Posttranslational modification of tubulin by palmitoylation: II. Identification
      of sites of palmitoylation.
AB  - As shown in the companion article, tubulin is posttranslationally modified in
      vivo by palmitoylation. Our goal in this study was to identify the palmitoylation
      sites by protein structure analysis. To obtain quantities of palmitoylated
      tubulin required for this analysis, a cell-free system for enzymatic
      [3H]palmitoylation was developed and characterized in our companion article. We
      then developed a methodology to examine directly the palmitoylation of all 451
      amino acids of alpha-tubulin. 3H-labeled palmitoylated alpha-tubulin was cleaved
      with cyanogen bromide (CNBr). The CNBr digest was resolved according to peptide
      size by gel filtration on Sephadex LH60 in formic acid:ethanol. The position of
      3H-labeled palmitoylated amino acids in peptides could not be identified by
      analysis of the Edman degradation sequencer product because the palmitoylated
      sequencer products were lost during the final derivatization step to
      phenylthiohydantoin derivatives. Modification of the gas/liquid-phase sequencer
      to deliver the intermediate anilinothiozolinone derivative, rather than the
      phenylthiohydantoin derivative, identified the cycle containing the 3H-labeled
      palmitoylated residue. Therefore, structure analysis of peptides obtained from
      gel filtration necessitated dual sequencer runs of radioactive peptides, one for
      sequence analysis and one to identify 3H-labeled palmitoylated amino acids.
      Further cleavage of the CNBr peptides by trypsin and Lys-C protease, followed by
      gel filtration on Sephadex LH60 and dual sequencer runs, positioned the 3H
      labeled palmitoylated amino acid residues in peptides. Integration of all the
      available structural information led to the assignment of the palmitoyl moiety to
      specific residues in alpha-tubulin. The palmitoylated residues in alpha-tubulin
      were confined to cysteine residues only. The major site for palmitoylation was
      cysteine residue 376.

PMID- 9247643
TI  - Posttranslational modification of tubulin by palmitoylation: I. In vivo and cell
      free studies.
AB  - It is well established that microtubules interact with intracellular membranes of
      eukaryotic cells. There is also evidence that tubulin, the major subunit of
      microtubules, associates directly with membranes. In many cases, this association
      between tubulin and membranes involves hydrophobic interactions. However, neither
      primary sequence nor known posttranslational modifications of tubulin can account
      for such an interaction. The goal of this study was to determine the molecular
      nature of hydrophobic interactions between tubulin and membranes. Specifically, I
      sought to identify a posttranslational modification of tubulin that is found in
      membrane proteins but not in cytoplasmic proteins. One such modification is the
      covalent attachment of the long chain fatty acid palmitate. The possibility that
      tubulin is a substrate for palmitoylation was investigated. First, I found that
      tubulin was palmitoylated in resting platelets and that the level of
      palmitoylation of tubulin decreased upon activation of platelets with thrombin.
      Second, to obtain quantities of palmitoylated tubulin required for protein
      structure analysis, a cell-free system for palmitoylation of tubulin was
      developed and characterized. The substrates for palmitoylation were
      nonpolymerized tubulin and tubulin in microtubules assembled with the slowly
      hydrolyzable GTP analogue guanylyl-(alpha, beta)-methylene-diphosphonate.
      However, tubulin in Taxol-assembled microtubules was not a substrate for
      palmitoylation. Likewise, palmitoylation of tubulin in the cell-free system was
      specifically inhibited by the antimicrotubule drugs Colcemid, podophyllotoxin,
      nocodazole, and vinblastine. These experiments identify a previously unknown
      posttranslational modification of tubulin that can account for at least one type
      of hydrophobic interaction with intracellular membranes.

PMID- 9247645
TI  - Sec3p is involved in secretion and morphogenesis in Saccharomyces cerevisiae.
AB  - Two new temperature-sensitive alleles of SEC3, 1 of 10 late-acting SEC genes
      required for targeting or fusion of post-Golgi secretory vesicles to the plasma
      membrane in Saccharomyces cerevisiae, were isolated in a screen for temperature
      sensitive secretory mutants that are synthetically lethal with sec4-8. The new
      sec3 alleles affect early as well as late stages of secretion. Cloning and
      sequencing of the SEC3 gene revealed that it is identical to profilin synthetic
      lethal 1 (PSL1). The SEC3 gene is not essential because cells depleted of Sec3p
      are viable although slow growing and temperature sensitive. All of the sec3
      alleles genetically interact with a profilin mutation, pfy1-111. The SEC3 gene in
      high copy suppresses pfy1-111 and sec5-24 and causes synthetic growth defects
      with ypt1, sec8-9, sec10-2, and sec15-1. Actin structure is only perturbed in
      conditions of chronic loss of Sec3p function, implying that Sec3p does not
      directly regulate actin. All alleles of sec3 cause bud site selection defects in
      homozygous diploids, as do sec4-8 and sec9-4. This suggests that SEC gene
      products are involved in determining the bud site and is consistent with a role
      for Sec3p in determining the correct site of exocytosis.

PMID- 9247646
TI  - Differential localization of myosin and myosin phosphatase subunits in smooth
      muscle cells and migrating fibroblasts.
AB  - Myosin II light chains (MLC20) are phosphorylated by a Ca2+/calmodulin-activated
      kinase and dephosphorylated by a phosphatase that has been purified as a trimer
      containing the delta isoform of type 1 catalytic subunit (PP1C delta), a myosin
      binding 130-kDa subunit (M130) and a 20-kDa subunit. The distribution of M130 and
      PP1C as well as myosin II was examined in smooth muscle cells and fibroblasts by
      immunofluorescence microscopy and immunoblotting after differential extraction.
      Myosin and M130 colocalized with actin stress fibers in permeabilized cells.
      However, in nonpermeabilized cells the staining for myosin and M130 was
      different, with myosin mostly at the periphery of the cell and the M130 appearing
      diffusely throughout the cytoplasm. Accordingly, most M130 was recovered in a
      soluble fraction during permeabilization of cells, but the conditions used
      affected the solubility of both M130 and myosin. The PP1C alpha isoform
      colocalized with M130 and also was in the nucleus, whereas the PP1C delta isoform
      was localized prominently in the nucleus and in focal adhesions. In migrating
      cells, M130 concentrated in the tailing edge and was depleted from the leading
      half of the cell, where double staining showed myosin II was present. Because the
      tailing edge of migrating cells is known to contain phosphorylated myosin,
      inhibition of myosin LC20 phosphatase, probably by phosphorylation of the M130
      subunit, may be required for cell migration.

PMID- 9247647
TI  - Immunochemical analysis of kinesin light chain function.
AB  - The kinesin heterotetramer consists of two heavy and two light chains. Kinesin
      light chains have been proposed to act in binding motor protein to cargo, but
      evidence for this has been indirect. A library of monoclonal antibodies directed
      against conserved epitopes throughout the kinesin light chain sequence were used
      to map light chain functional architecture and to assess physiological functions
      of these domains. Immunocytochemistry with all antibodies showed a punctate
      pattern that was detergent soluble. A monoclonal antibody (KLC-All) made against
      a highly conserved epitope in the tandem repeat domain of light chains inhibited
      fast axonal transport in isolated axoplasm by decreasing both the number and
      velocity of vesicles moving, whereas an antibody against a conserved amino
      terminus epitope had no effect. KLC-All was equally effective at inhibiting both
      anterograde and retrograde transport. Neither antibody inhibited microtubule
      binding or ATPase activity in vitro. KLC-All was unique among antibodies tested
      in releasing kinesin from purified membrane vesicles, suggesting a mechanism of
      action for inhibition of axonal transport. These results provide further evidence
      that conventional kinesin is a motor for fast axonal transport and demonstrate
      that kinesin light chains play an important role in kinesin interaction with
      membranes.

PMID- 9247648
TI  - Subcellular distribution and targeting of the intracellular chloride channel p64.
AB  - p64 is an intracellular chloride channel originally identified in bovine kidney
      microsomes. Using a combination of immunofluorescent and electron microscopic
      technique, we demonstrate that p64 resides in the limiting membranes of
      perinuclear dense core vesicles which appear to be regulated secretory vesicles.
      Heterologous expression of p64 in PancI cells, a cell type which does not
      normally express p64, results in targeting to a similar compartment. Mutagenesis
      experiments demonstrate that both the N- and C-terminal domains of the protein
      independently contribute to subcellular distribution of the protein. The C
      terminal domain functions to prevent expression of p64 on the plasma membrane and
      the N-terminal domain is necessary to deliver p64 to the appropriate membrane
      compartment.

PMID- 9247649
TI  - An N-terminal fragment of titin coupled to green fluorescent protein localizes to
      the Z-bands in living muscle cells: overexpression leads to myofibril
      disassembly.
AB  - Cultures of nonmuscle cells, skeletal myotubes, and cardiomyocytes were
      transfected with a fusion construct (Z1.1GFP) consisting of a 1.1-kb cDNA (Z1.1)
      fragment from the Z-band region of titin linked to the cDNA for green fluorescent
      protein (GFP). The Z1.1 cDNA encodes only 362 amino acids of the approximately
      2000 amino acids that make up the Z-band region of titin; nevertheless, the
      Z1.1GFP fusion protein targets the alpha-actinin-rich Z-bands of contracting
      myofibrils in vivo. This fluorescent fusion protein also localizes in the nascent
      and premyofibrils at the edges of spreading cardiomyocytes. Similarly, in
      transfected nonmuscle cells, the Z1.1GFP fusion protein localizes to the alpha
      actinin-containing dense bodies of the stress fibers in vivo. A dominant negative
      phenotype was also observed in living cells expressing high levels of this
      Z1.1GFP fusion protein, with myofibril disassembly occurring as titin-GFP
      fragments accumulated. These data indicate that the Z-band region of titin plays
      an important role in maintaining and organizing the structure of the myofibril.
      The Z1.1 cDNA was derived from a chicken cardiac lambda gt11 expression library,
      screened with a zeugmatin antibody. Recent work has suggested that zeugmatin is
      actually part of the N-terminal region of the 81-kb titin cDNA. A reverse
      transcriptase polymerase chain reaction using a primer from the distal end (5'
      end) of the Z1.1 zeugmatin cDNA and a primer from the nearest known proximal (3'
      end) chicken titin (also called connectin) cDNA resulted in a predicted 0.3-kb
      polymerase chain reaction product linking the two known chicken titin cDNAs to
      each other. The linking region had a 79% identity at the amino acid level to
      human cardiac titin. This result and a Southern blot analysis of chicken genomic
      DNA hybridized with Z1.1 add further support to our original suggestion that
      zeugmatin is a proteolytic fragment from the N-terminal region of titin.

PMID- 9247650
TI  - Cytoplasmic tails of beta 1, beta 2, and beta 7 integrins differentially regulate
      LFA-1 function in K562 cells.
AB  - The beta 2 integrin lymphocyte function-associated antigen 1 (LFA-1) mediates
      activation-dependent adhesion of lymphocytes. To investigate whether lymphocyte
      specific elements are essential for LFA-1 function, we expressed LFA-1 in the
      erythroleukemic cell line K562, which expresses only the integrin very late
      antigen 5. We observed that LFA-1-expressing K562 cannot bind to intercellular
      adhesion molecule 1-coated surfaces when stimulated by phorbol 12-myristate 13
      acetate (PMA), whereas the LFA-1-activating antibody KIM185 markedly enhanced
      adhesion. Because the endogenously expressed beta 1 integrin very late antigen 5
      is readily activated by PMA, we investigated the role of the cytoplasmic domain
      of distinct beta subunits in regulating LFA-1 function. Transfection of chimeric
      LFA-1 receptors in K562 cells reveals that replacement of the beta 2 cytoplasmic
      tail with the beta 1 but not the beta 7 cytoplasmic tail completely restores PMA
      responsiveness of LFA-1, whereas a beta 2 cytoplasmic deletion mutant of LFA-1 is
      constitutively active. Both deletion of the beta 2 cytoplasmic tail or
      replacement by the beta 1 cytoplasmic tail alters the localization of LFA-1 into
      clusters, thereby regulating LFA-1 activation and LFA-1-mediated adhesion to
      intercellular adhesion molecule 1. These data demonstrate that distinct signaling
      routes activate beta 1 and beta 2 integrins through the beta-chain and hint at
      the involvement of lymphocyte-specific signal transduction elements in beta 2 and
      beta 7 integrin activation that are absent in the nonlymphocytic cell line K562.

PMID- 9247651
TI  - Aip3p/Bud6p, a yeast actin-interacting protein that is involved in morphogenesis
      and the selection of bipolar budding sites.
AB  - A search for Saccharomyces cerevisiae proteins that interact with actin in the
      two-hybrid system and a screen for mutants that affect the bipolar budding
      pattern identified the same gene, AIP3/BUD6. This gene is not essential for
      mitotic growth but is necessary for normal morphogenesis. MATa/alpha daughter
      cells lacking Aip3p place their first buds normally at their distal poles but
      choose random sites for budding in subsequent cell cycles. This suggests that
      actin and associated proteins are involved in placing the bipolar positional
      marker at the division site but not at the distal tip of the daughter cell. In
      addition, although aip3 mutant cells are not obviously defective in the initial
      polarization of the cytoskeleton at the time of bud emergence, they appear to
      lose cytoskeletal polarity as the bud enlarges, resulting in the formation of
      cells that are larger and rounder than normal. aip3 mutant cells also show
      inefficient nuclear migration and nuclear division, defects in the organization
      of the secretory system, and abnormal septation, all defects that presumably
      reflect the involvement of Aip3p in the organization and/or function of the actin
      cytoskeleton. The sequence of Aip3p is novel but contains a predicted coiled-coil
      domain near its C terminus that may mediate the observed homo-oligomerization of
      the protein. Aip3p shows a distinctive localization pattern that correlates well
      with its likely sites of action: it appears at the presumptive bud site prior to
      bud emergence, remains near the tips of small bund, and forms a ring (or pair of
      rings) in the mother-bud neck that is detectable early in the cell cycle but
      becomes more prominent prior to cytokinesis. Surprisingly, the localization of
      Aip3p does not appear to require either polarized actin or the septin proteins of
      the neck filaments.

PMID- 9247653
TI  - Dakin's solution revisited.

PMID- 9247654
TI  - The Fortin finger test: an indicator of sacroiliac pain.
AB  - Simple and reliable diagnostic aids need to be available for clinicians to
      consider sacroiliac joint dysfunction in the differential diagnosis of low back
      pain. The Fortin finger test was used as a means to identify patients with low
      back pain and sacroiliac joint dysfunction. Provocation-positive sacroiliac joint
      injections were used to ratify or refute the applicability of this new clinical
      sign for identification of patients with sacroiliac joint dysfunction. Sixteen
      subjects were chosen from 54 consecutive patients by using the Fortin finger
      test. All 16 patients subsequently had provocation-positive joint injections
      validating sacroiliac joint abnormalities. A subset of 10 individuals underwent
      additional evaluation to exclude the possibility of confounding discogenic or
      posterior joint pain sources. All 10 patients had no indication of either
      discogenic or zygapophyseal joint pain generators. These results indicate that
      positive findings of the Fortin finger test, a simple diagnostic measure,
      successfully identifies patients with sacroiliac joint dysfunction.

PMID- 9247652
TI  - sn-1,2-diacylglycerol and choline increase after fertilization in Xenopus laevis.
AB  - sn-1,2-Diacylglycerol (DAG) mass and translocation of protein kinase C alpha and
      beta to a membrane fraction increased approximately 7 min after insemination of
      Xenopus laevis eggs. The DAG mass increase of 48 pmol (from 62 to 110 pmol/cell)
      was greater than that for inositol 1,4,5-trisphosphate (IP3; an increase of
      approximately 170 fmol or approximately 280-fold smaller than the DAG increase),
      and DAG peaks approximately 5 min after IP3. Choline mass (a measure of
      phosphatidyl choline-specific phospholipase D) also peaked before DAG and the
      choline increase (134 pmol/cell) was greater than that of DAG. There was no
      detectable change in phosphocholine mass (a measure of phosphatidylcholine
      specific phospholipase C). During first cleavage, DAG decreased, PKC
      translocation was low, and choline increased and peaked (whereas published work
      shows an increase in IP3 mass). Artificial elevation of intracellular calcium
      ([Ca2+]i) increased DAG levels but prevention of the [Ca2+]i increase after
      fertilization did not block DAG production. Thus, sperm stimulate production of
      DAG and choline through [Ca2+]i-independent and [Ca2+]i-dependent paths.

PMID- 9247655
TI  - Neuromas and gaps of sensory nerves of the hand: management using vein conduits.
AB  - This study analyzed the efficacy of an interposed vein conduit graft in
      eliminating symptoms of painful neuroma of sensory nerves of the hand and
      preventing recurrence after excising the pathologic tissue and bridging the
      concomitant gap with the distal nerve segment. Twenty-three patients underwent
      reconstruction of 25 palmar sensory nerve gaps ranging from 12 mm to 28 mm, as
      well as 2 dorsal gaps of 32 mm and 35 mm, respectively. Eighteen patients had
      symptomatic painful neuromas. Subjective and objective evaluation criteria were
      employed for assessment and were compared with data obtained from primary direct
      suturing in 25 digital nerves of 21 patients. Electrophysiologic measurements,
      including sensory nerve action potential and conduction velocity, were similar,
      with both groups having values significantly lower than normal control values.
      Two-point discrimination measurements were slightly inferior for the vein conduit
      reconstructed nerves compared with results attained after direct suturing.
      However, neuroma symptoms were eliminated, and in combination with the return of
      adequate sensibility, all but 1 patient resumed full hand function.

PMID- 9247656
TI  - Irreducible superior dislocation of the patella requiring open reduction.
AB  - The authors describe a case of superior dislocation of patella that was
      irreducible by closed methods. Extensive review of the literature revealed that
      this is the first case reported in which an open reduction was needed to reduce a
      superior dislocation of the patella to unlock the osteophytes, which were
      blocking the closed reduction.

PMID- 9247657
TI  - Demonstration of avulsion of the triceps tendon in an adolescent by magnetic
      resonance imaging.
AB  - Avulsion of the triceps tendon is an uncommon injury typically occurring in
      skeletally mature individuals. Although the diagnosis can be suggested by the
      physical findings and initial radiographs, it may be missed, especially when
      severe swelling of the soft tissues prevents an accurate physical examination and
      the radiographs do not show a small fragment of bone accompanying the avulsed
      tendon. This report describes an avulsion of the triceps tendon in an adolescent
      boy. Magnetic resonance imaging was useful in confirming the diagnosis.

PMID- 9247658
TI  - Reconstruction of the heel pad in ankle disarticulation with a free muscle
      transfer.
AB  - An otherwise healthy 17-year-old young man developed bilateral heel pad necrosis
      due to meningococcemia, adult respiratory distress syndrome, and disseminated
      intravascular coagulation. Bilateral ankle disarticulation amputations were
      salvaged by use of a dorsally based local flap on one residual limb and a free
      muscle transfer to reconstruct the weight-bearing surface of the contralateral
      residual limb. The case report illustrates two methods of unusual salvage of the
      end-bearing, weight-bearing surface of the residual limbs in a bilateral end
      bearing amputation.

PMID- 9247659
TI  - An unusual midfoot dislocation: a case report.
AB  - An unusual case of dislocation of the midfoot through the calcaneocuboid and
      naviculocuneiform joints is presented. The prognosis is excellent for most
      midfoot dislocations, as long as they are recognized and treated early.

PMID- 9247660
TI  - Voluntary scapulothoracic subluxation: a case report.
AB  - Dislocation of the scapula is a rare event, usually associated with massive
      trauma and injury. We report a case of a patient for whom dislocation was the
      sole presentation. The possibility of voluntary dislocation for secondary gain
      was suspected, but because of perceived progressive brachial plexus involvement,
      urgent closed reduction was undertaken and led to resolution of the neurologic
      symptoms. The patient returned 1 year later with similar complaints and findings,
      but declined another closed reduction attempt when offered only an interscalene
      regional block as pain relief. The diagnosis of voluntary dislocation should be
      considered in a patient presenting with superior and lateral migration of the
      scapula, without a history of trauma.

PMID- 9247661
TI  - Vertical displacement of the symphysis pubis in unilateral open book pelvic
      injury.
AB  - Nineteen cases of external rotation (open book) injury of the pelvis were studies
      retrospectively. An apparent vertical displacement of the hemipelvis was detected
      on anteroposterior radiographic views in association with the separation of the
      symphysis pubis and opening of the sacroiliac joint. This could be confused with
      a vertically unstable situation; however, careful examination of the radiographs
      revealed that the public bone on the side of injury was displaced inferiorly. The
      articular portion of the corresponding sacroiliac joint on computed tomography
      was opened anteriorly, and the hemipelvis on the same side was externally rotated
      in all cases (indicating that the posterior sacroiliac ligaments were intact). An
      anatomic study was then performed on 10 cadaveric pelves. The symphysis pubis and
      the anterior sacroiliac ligament on one side were sharply disrupted, and the
      pelvis was gradually externally rotated. The pubic bone on the side of the
      sacroiliac disruption displaced inferiorly as the external rotation progressed.
      It is important to differentiate between the inferiorly displaced pubic bone on
      the side of injury in cases of external rotation injury and the superiorly
      displaced pubic bone on the side of injury in cases of vertically unstable pelvic
      injuries. This may eliminate unnecessary procedures such as skeletal traction or
      pinning of the sacroiliac joint.

PMID- 9247662
TI  - C-arm manipulation using a sterile disposable lamp handle.
AB  - Portable C-arm fluoroscopy is often used in the operating room. We describe a
      sterile technique that enables the physician to position the C-arm without
      requiring the use of a sterile drape.

PMID- 9247663
TI  - Screening for prostatic carcinoma: case finding is not the problem.

PMID- 9247664
TI  - Recommendations for the reliable detection of illicit drugs in urine in the
      European Union, with special attention to the workplace. EU Toxicology Experts
      working Group.

PMID- 9247665
TI  - The role of the laboratory in the diagnosis of Cushing's syndrome.

PMID- 9247666
TI  - Relationship between lipoprotein (a) and both stroke and carotid atheroma.
AB  - In vitro studies provide mechanisms by which elevated lipoprotein (a) [Lp(a)]
      concentrations may promote both thrombosis and atherogenesis. Case-control
      studies have reported raised Lp(a) concentrations in patients with stroke, but
      prospective studies have failed to confirm the association. A potential
      confounding factor is that Lp(a) may rise acutely after stroke. We determined
      Lp(a) concentrations in 164 patients studied at least 21 days after stroke or
      transient ischaemic attack, and in 91 controls. In the patient group we
      correlated Lp(a) concentrations with both the degree of carotid stenosis
      estimated on duplex ultrasonography, and with stroke subtype (large vessel
      disease, lacunar infarction, and cardioembolic and unknown pathogenesis). There
      was no difference between Lp(a) concentration in cases and controls [median
      (quartiles) 0.10 (0.04, 0.39) versus 0.12 (0.04, 0.30) g/L, P = 0.34]. There was
      no difference in the proportion of cases compared with controls with a markedly
      elevated Lp(a) of > 0.4 g/L (21.3 versus 16.5%, P = 0.34). There was non
      significant trend towards higher median Lp(a) concentrations in women [median
      (quartiles) 0.16 (0.04, 0.32) g/L versus 0.12 (0.04, 0.28) g/L, P = 0.3]. In view
      of this trend we analysed the differences between cases and controls for each sex
      separately. Lp(a) concentrations in men were median (quartiles) 0.08 (0.04, 0.26)
      g/L in the 101 cases and 0.12 (0.04, 0.28) g/L in the 43 controls (P = 0.6).
      Lp(a) concentrations in women were median (quartiles) 0.25 (0.04, 0.44) g/L in
      the 63 cases, and 0.16 (0.04, 0.32) g/L in the 48 controls (P = 0.16). Within the
      patient group there was no difference between Lp(a) concentrations in the
      different stroke subgroups. There was no relationship between Lp(a)
      concentrations and mean percentage carotid stenosis (rs = 0.14, P = 0.07). Our
      results suggest that in an unselected population of men studied more than 3 weeks
      post event there is no relationship between lipoprotein(a) concentrations and
      either stroke/transient ischaemic attack, or carotid atheroma. The relationship
      in women requires further study.

PMID- 9247667
TI  - Serum S-100 protein, relationship to clinical outcome in acute stroke.
AB  - The clinical significance of serum S-100 protein, a protein released by damaged
      brain tissue, was assessed in patients with acute ischaemic or haemorrhagic
      stroke and matched controls. Serum S-100 protein concentration was significantly
      elevated in patients with ischaemic stroke [median (SQR): 0.27 (0.90)
      microgram/L, n = 68] and haemorrhagic stroke [0.43 (0.23 microgram/L, n = 13]
      compared to controls [0.11 (0.03) microgram/L, n = 51, P < 0.0001]. Although
      patients with haemorrhagic stroke had higher serum S-100 concentrations compared
      to patients with ischaemic stroke, this was not quite statistically significant.
      Serum S-100 concentrations were related to infarct size, large (total anterior
      circulation) infarcts concentrations having the highest [0.40 (0.22)
      microgram/L], and small vessel ('lacunar') infarcts concentrations having the
      lowest [0.20 (0.60) microgram/L, P < 0.0005] concentrations. S-100 protein
      concentration was also significantly related to clinical outcome at three months
      measured using three disability and handicap scales (n = 81): modified Barthel
      index (rs = -0.285, P = 0.01), modified Rankin score (rs = 0.313, P = 0.004) and
      Lindley score (rs = 0.262, P = 0.018) with high values associated with poor
      clinical outcome. Similarly high values of serum S-100 protein were observed in
      patients who died or were discharged to an institution [median (SQR): 0.63 (0.29)
      microgram/L and 0.37 (0.13) microgram/L, respectively compared to those who were
      discharged home [0.26 (0.11) microgram/L, P = 0.13]. The present study suggests
      measurement of serum S-100 protein could be a useful prognostic marker of
      clinical outcome in acute stroke. Whether S-100 concentrations can be altered by
      therapeutic intervention in acute stroke remains to be elucidated.

PMID- 9247668
TI  - A comparison of three procedures for the detection of Bence-Jones proteinuria.
AB  - A traditional electrophoretic procedure for detection of Bence-Jones proteinuria,
      employing Amido black stain on 200-fold concentrated urine, has been compared to
      two procedures employing highly sensitive protein stains not requiring prior
      urine concentration. All three procedures were carried out on 80 random urine
      samples screened for Bence-Jones proteinuria and 10 samples were provided by
      patients attending a myeloma clinic. A new procedure employing modified Coomassie
      brilliant blue stain on unconcentrated urine showed comparable sensitivity to the
      established procedure (82% versus 88%, respectively) and specificity (77% versus
      74%, respectively), when assessed against immunofixation as a reference method.
      However, the new method is considerably quicker and cheaper. A second method,
      employing Gold stain, showed enhanced sensitivity (94% versus 88% for Amido
      black) but lower specificity (62% versus 74% for Amido black). However, this
      method is labour intensive and relatively expensive. Our data suggest that the
      procedure employing modified Coomassie brilliant blue may be a suitable
      alternative to the traditional procedure commonly used in many clinical
      laboratories.

PMID- 9247669
TI  - The measurement of morphine in the hair of heroin abusers.
AB  - Several techniques have been described for the determination of morphine in hair
      as a method of monitoring past heroin use. However, although some of the
      techniques [notably radioimmunoassay (RIA)] may appear relatively simple to
      perform, any results obtained must be interpreted with caution. In this study,
      hair specimens from four known heroin abusers were sectionally analysed by a
      specific RIA for morphine. Prior to analysis, all hair sections were cleaned to
      remove any possible surface contamination. Five different hair digestion
      procedures were evaluated to determine the most effective method that could be
      used to liberate morphine from hair. The greatest analytical recovery was
      obtained by incubation with 1.0 M sodium hydroxide for 18 h at 55 degrees C,
      neutralization with 1.0 M hydrochloric acid, and pH adjustment with 0.1 M
      phosphate buffer (pH 7.0). The morphine concentrations detected in the hair
      specimens ranged from 0.5 to 13.2 ng/mg of hair. It was also found that the use
      of shorter length segments (e.g. 1 cm length) gave a clearer, more detailed
      picture of the historic pattern of heroin use in the four subjects studied.

PMID- 9247670
TI  - New enzymatic assay with urea amidolyase for determining potassium in serum.
AB  - We developed a new simple assay for potassium ion in serum using urea amidolyase
      (UAL) from yeast sp. The method is based on activation of the enzyme by potassium
      ion. We eliminated endogenous ammonium ion by use of glutamate dehydrogenase
      (GLDH), and then monitored the production of ammonium ion by UAL, urea, ATP,
      bicarbonate and magnesium ions. Ammonium ion was produced proportional to the
      potassium ion concentration and was determined by adding GLDH to produce NADP+ in
      the presence of 2-oxoglutarate and NADPH. We monitored the change of absorbance
      at 340 nm. The inhibitory effect of calcium ion to this assay was eliminated by
      adding glycoletherdiamine-N, N, N', N'-tetraacetic acid to the reaction. The
      within-assay coefficients of variation (CV) of this method were 0.9-1.55% (n =
      10) at 3.32-6.18 mmol/L. Day-to-day CVs ranged from 1.49% to 2.46%. The
      analytical recovery was 96-108%. The correlation coefficient between the values
      obtained by our method (y) and those by the ion-selective electrode (ISE) method
      (x) was 0.994 (y = 1.032x-0.166 mmol/L, Syx = 0.110, n = 100). The presence of
      bilirubin, haemoglobin or other ions did not affect this assay, confirming the
      usefulness of this assay for clinical purposes.

PMID- 9247671
TI  - Real time validation of paediatric biochemical reports using the Valab-Biochem
      system.
AB  - Validation of biochemical reports must be fast and clinically accurate to be of
      assistance to clinicians. Considerable skill is required to analyse the
      consistency of different data in the report and to consider influences on the
      data. When performed throughout the day, such analysis is time-consuming and
      uncertain. We therefore decided to use a computer-assisted validation system,
      Valab-Biochem. Its decisions result from a decision tree based primarily on the
      intrinsic consistency of the data, validation ranges and patients' sex, age and
      hospital ward. Three hundred randomly chosen reports were simultaneously
      submitted to Valab-Biochem and to five biologists in order to analyse the
      computer's findings. The sensitivity of Valab-Biochem was 80% compared to
      biologists' consensus decision, which was taken as the gold standard. The
      specificity was 78%. This system provided autonomous assessment of the reports
      and could be used as an initial screen to assist biologists and focus attention
      on potentially inconsistent reports.

PMID- 9247672
TI  - Two years' experience with an enhanced chemiluminescent assay for neonatal blood
      spot TSH.
AB  - We have developed a blood spot assay for thyroid stimulating hormone (TSH) based
      on the Amerlite TSH-30 serum assay for use in the Welsh neonatal hypothyroid
      screening programme. A total of 67,656 infants were screened in 1994 and 1995,
      and 28 cases of primary hypothyroidism were detected, giving a prevalence of one
      in 2416. The method is sensitive and rapid, results being available within 3 h of
      receipt of samples. The assay enables much faster detection of primary
      hypothyroidism than was previously possible, and therefore contributes to earlier
      treatment of affected infants.

PMID- 9247674
TI  - Clinical significance of urinary human tissue non-specific alkaline phosphatase
      (hTNAP) in pre-eclampsia and eclampsia.
AB  - The aim of this work was to determine the levels of urinary human tissue non
      specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia in order to
      assess renal tubular damage. Urine samples were collected from 26 mild pre
      eclamptic, 26 were pre-eclamptic, 20 eclamptic patients and 20 healthy pregnant
      women (controls) in their late third trimester. Urinary hTNAP/creatinine
      (hTNAP/cr) in severe pre-eclampsia and eclampsia were significantly higher than
      in controls. Urinary hTNAP/cr was increased in 23%, 77% and 90% of cases of mild
      pre-eclampsia, severe pre-eclampsia and eclampsia, respectively, indicating that
      the increase correlates with the severity of the disease. Marked elevation or
      urinary hTNAP/cr was also associated with bad fetal outcome. These results
      provide additional evidence for renal tubular damage in pre-eclampsia and
      eclampsia.

PMID- 9247673
TI  - A semiautomated alanine:glyoxylate aminotransferase assay for the tissue
      diagnosis of primary hyperoxaluria type 1.
AB  - We have developed a sensitive assay for the measurement of alanine:glyoxylate
      aminotransferase (EC 2.6.1.44) activity in human liver. The assay is partly
      automated, and takes into consideration the sensitivity of the reaction to pH and
      to glyoxylate concentration. It is less subject to interference from other
      enzymes utilizing glyoxylate and to chemical interference from glyoxylate itself
      and can therefore be used without correction for cross-over by
      glutamate:glyoxylate aminotranferase (EC 2.6.1.4). The assay allows clear
      discrimination between normal and affected livers and is sufficiently sensitive
      to measure enzyme activity in fetal liver samples. Enzyme activity ranged from
      17.9 to 38.5 mumol/h/mg protein in control livers (n = 9) and 0.8 to 9.5
      mumol/h/mg protein in 30 of 39 hyperoxaluric patients studied. Normal
      alanine:glyoxylate aminotransferase activity (from 22.8 to 45.5 mumol/h/mg
      protein) allowed exclusion of primary hyperoxaluria type 1 in the other nine
      hyperoxaluric patients.

PMID- 9247675
TI  - Enhanced chemiluminescent assay for measuring the total antioxidant capacity of
      serum, saliva and crevicular fluid.
AB  - This paper reports the development of an enhanced chemiluminescent (ECL) assay
      for measuring the total antioxidant (AO) capacity of serum, saliva and a fluid
      collectable from the gum margin called gingival crevicular fluid (GCF). The
      theory behind the assay is explained, and the optimum conditions for the assay,
      and for storage of reagents and clinical samples is described. Calibration lines
      were linear (R > or = 0.99; P < 0.0001) and the within batch coefficient of
      variations for a water soluble vitamin E analogue (Trolox), serum and saliva
      samples were < 5%. In saliva and GCF, a characteristic AO response not seen in
      serum of the same patients, was identified. Total peripheral (serum) and local
      (saliva) AO capacities (mumol/L Trolox) were investigated in patients with (n =
      18) and without (n = 16) adult periodontitis. Serum AO status did not differ
      between groups. Salivary total AO concentrations were lower in the peridontitis
      (P) group [175 (53) mumol/L] than in the non-periodontitis (NP) group [254 (110)
      mumol/L1: P < 0.01], as were saliva:serum AO ratio's [0.37 (0.11) versus 0.5
      (0.18): P < 0.01]. Periodontitis patients may have a reduced salivary AO
      concentration, which could result from, or predispose to, the damaging effects of
      reactive oxygen species (ROS). The potential for ROS production in the oral and
      periodontal environment may explain the presence of a specific antioxidant in
      oral fluids that is not detectable in serum. The ECL assay described provides a
      rapid, simple and reproducible method of measuring total antioxidant defence in
      small volumes of biological fluids.

PMID- 9247676
TI  - An assessment of the Boehringer Advantage blood glucose meter.

PMID- 9247677
TI  - Urinary 5-hydroxyindole-acetic acid by high-performance liquid chromatography
      with electrochemical detection.

PMID- 9247678
TI  - A common genetic variant affecting folate metabolism is not over-represented in
      chronic fatigue syndrome.

PMID- 9247679
TI  - More on the inhibition of the urease reaction by boric acid.

PMID- 9247680
TI  - Asymptomatic cholesteryl ester storage disease in an adult controlled with
      simvastatin.

PMID- 9247681
TI  - Selenium: an acute-phase reactant?

PMID- 9247682
TI  - A case of coeliac disease detected via raised 5-hydroxytryptamine and 5
      hydroxyindoleacetic acid.

PMID- 9247683
TI  - Biochemical implications of ecstasy toxicity.

PMID- 9247684
TI  - General principles for the radiation protection of workers.

PMID- 9247685
TI  - Taking care of business.

PMID- 9247686
TI  - Over representation of Burmese cats with diabetes mellitus.
AB  - OBJECTIVE: To determine if Burmese cats in Queensland have an increased risk of
      diabetes mellitus. DESIGN: A retrospective study of diabetic and nondiabetic cats
      that had blood submitted to a veterinary clinical laboratory over a 22 month
      study period. SAMPLE POPULATION: 4402 cats PROCEDURE: Cats were considered
      diabetic if blood glucose concentration was > 11 mmol/L and fructosamine was >
      406 mumol/L or hydroxybutyrate was > 1 mmol/L. Cats were grouped into Burmese and
      non-Burmese. Adjusted odds ratios of diabetes were calculated for breed, gender
      and age group amongst cats with blood glucose > 11 mmol/L. RESULTS: Burmese cats
      comprised 20% of 45 diabetic cats of known breed, which was higher (P < 0.001)
      than among the normoglycemic reference population of 2203 cats (7% Burmese).
      There were more females among the diabetic Burmese (62%), but this did not differ
      (P > 0.05) from the Burmese reference population (45% females). In contrast,
      males seemed to predominate among diabetic non-Burmese (63%), although this also
      did not differ (P > 0.05) from the reference population (55%) of from diabetic
      Burmese (38% males). The majority (90%) of diabetic cats were older than 6 years,
      irrespective of breed (median age 12 years, interquartile range 10 to 13 years).
      This was higher (chi(2) = 8.13, P < 0.005) than among the normoglycaemic
      reference population, where 69% were older than 6 years. CONCLUSIONS: Burmese
      cats were significantly over represented among cats with diabetes mellitus.
      Irrespective of breed, the risk of diabetes in the study population increased
      with age.

PMID- 9247687
TI  - Efficacy of praziquantel in the treatment of green sea turtles with spontaneous
      infection of cardiovascular flukes.
AB  - OBJECTIVE: To assess the efficacy of praziquantel as a treatment for
      cardiovascular flukes in turtles. PROCEDURE: Six green sea turtles (Chelonia
      mydas) spontaneously infected with cardiovascular flukes (Digenea: Spirorchiidae)
      were treated orally with praziquantel, and necropsied 3 or 7 days later to look
      for flukes in the heart and major blood vessels. Six similar animals were
      maintained as untreated controls. RESULTS: Absence of flukes in treated, but not
      control turtles, indicated that a one day course of treatment at a dose rate of 3
      x 50 mg/kg body weight is effective. CONCLUSION: This result should be of value
      for preventing disease in wild caught green turtles introduced into farms or
      aquaria.

PMID- 9247689
TI  - Bilateral ureteral tears in a foal.

PMID- 9247688
TI  - An overview of the topical management of wounds.
AB  - Wounds in animals are a common and frequent reason for seeking veterinary
      attention. The way in which wounds are managed affect the rate of healing, the
      time to return to normal function, the final cosmetic appearance, and hence the
      satisfaction of customers. The management of wounds depends on the stage of wound
      healing and can include irrigation, mechanical and chemical debridement, the use
      of antiseptics and antimicrobials, adherent and nonadherent dressings, and
      miscellaneous topical applications such as aloe vera, honey and live yeast cell
      derivative. The advantages, disadvantages and indications for initial wound
      management, topical applicants and dressings are discussed.

PMID- 9247690
TI  - Veterinarians and the promotion of food safety on the farm.

PMID- 9247691
TI  - Review of oral rehydration solutions for horses with diarrhoea.

PMID- 9247692
TI  - Peripheral blood lymphocyte subsets in fleece rot-resistant and -susceptible
      sheep.
AB  - OBJECTIVE: To compare haematological values and lymphocyte phenotypes in the
      peripheral blood of fleece rot-resistant and -susceptible sheep. PROCEDURE:
      Experiments were conducted on 2- and 3-year-old Merino rams, flock 1 (17 rams)
      and flock 2 (32 rams), respectively. Within each flock, individual rams were
      classified as fleece rot-resistant or -susceptible, based on established
      criteria. Total and differential white cell counts, and indirect fluorescent
      antibody tests specific for B cells and T cells were performed on all sheep. The
      concentration of various subsets of circulating lymphocytes was then determined
      in each sheep. RESULTS: There were no significant differences between fleece rot
      resistant and -susceptible sheep from either flock in the mean total or
      differential white cell counts. However, fleece rot-resistant rams in flock 1 did
      have a significantly higher concentration of circulating SBU-T1+ cells than
      fleece rot-susceptible rams from the same flock. No such difference was noted in
      the rams from flock 2. While all rams in flock 1 were free of clinical fleece
      rot, 24 rams in flock 2 (comprising all 17 fleece rot-susceptible and 7 of 15
      fleece rot-resistant animals) had clinical signs of the disease. Fleece rot-free
      rams in this flock (irrespective of their classification as fleece rot-resistant
      or -susceptible) had significantly higher concentrations of circulating SBU-T1+
      cells compared with fleece rot-affected animals. They also had significantly
      higher concentrations of circulating B cells, and total lymphocytes. CONCLUSIONS:
      An examination of peripheral blood lymphocyte subsets in fleece rot-resistant and
      -susceptible sheep revealed a possible association between resistance to fleece
      rot and the concentration of circulating SBU-T1+ cells.

PMID- 9247693
TI  - Retrospective study of 60 cases of feline lymphosarcoma.
AB  - OBJECTIVE: To characterise epidemiological and clinical findings, and diagnostic
      procedures undertaken, in cats with lymphosarcoma at a veterinary teaching
      hospital. DESIGN: Retrospective case study. PROCEDURE: Hospital records were
      reviewed for 7159 cats, sick or healthy, examined during a 10-year period (1984
      to 1994). Sixty cats with lymphosarcoma were identified and classified by
      anatomical location of the tumor. Data on breed, age, sex, clinical signs and
      diagnostic procedures were collated. RESULTS: The prevalence of feline
      lymphosarcoma in the hospital population was 0.84%. Siamese cats appeared
      predisposed to lymphosarcoma but other purebreds were not. Males were somewhat
      overrepresented amongst affected cats. Similar numbers of cases (12 to 18) were
      seen in each of the four anatomic categories (multicentric, mediastinal,
      alimentary and extranodal). Cats with mediastinal lymphosarcoma were mostly young
      and Siamese. Clinical signs in affected cats were varied, usually multiple and
      often nonspecific. Two of 22 cases tested positive for feline leukaemia virus
      antigen in blood and 6 of 13 were positive for feline immunodeficiency virus
      antibody. CONCLUSIONS: Extranodal lymphosarcoma seemed more prevalent in this
      study than reported elsewhere. Siamese cats in the study population may have had
      a genetic predisposition to lymphosarcoma. Limited evidence suggested feline
      leukaemia virus may be less important, and feline immunodeficiency virus more
      important, in the local population than indicated in overseas reports. Additional
      studies are needed to investigate breed predisposition and feline leukaemia virus
      and feline immunodeficiency virus status in Australian cats with lymphosarcoma.

PMID- 9247694
TI  - Immune response to avian reovirus in chickens and protection against experimental
      infection.
AB  - OBJECTIVES: To assess the efficacy of the vaccination procedure and the effect of
      the transfer of maternal antibodies to progeny chickens on reovirus
      pathogenicity. DESIGN: To vaccinate chickens and challenge progeny chickens with
      high doses of homologous and heterologous viruses. PROCEDURE: High doses of
      reovirus strains RAM-1, 1091 and 724 were used to induce tenosynovitis lesions.
      High doses were produced by concentration of viruses grown in cell culture. Then
      similar doses of viruses were used to challenge immunised chickens progeny.
      RESULT: Vaccination of breeding hens with the RAM-1 strain of avian reovirus,
      which resulted in the passive transfer of neutralising antibody to progeny
      chickens, completely prevented the development of tenosynovitis in 80% of progeny
      chickens infected with the homologous virus. Even though multiple injections of
      hens resulted in broadening of the normal type-specificity of the neutralising
      antibody response against heterologous serotypes of avian reovirus, only marginal
      protection against strains of two heterologous serotypes of avian reovirus was
      obtained. CONCLUSIONS: A model for assessing the efficacy of vaccination against
      avian reovirus strains on clinical sign such as tenosynovitis was developed that
      overcome the normal low virulence of Australian strains of avian reovirus.
      Breeding hens can be immunised with Australian strain of avian reovirus with
      passive transfer of antibody via the yolk to the progeny chickens. Although the
      neutralising antibody response to three injections of inactivated virus decreased
      the specificity of the neutralising antibody response against antigenically
      heterologous strains of avian reovirus, the protective immunity appeared to
      retain type-specificity.

PMID- 9247695
TI  - Effect of transportation on lower respiratory tract contamination and peripheral
      blood neutrophil function.
AB  - OBJECTIVE: To evaluate the effect of transportation on lower respiratory tract
      contamination and peripheral blood neutrophil function in horses and to compare
      results from transported horses with those obtained in earlier experiments from
      horses confined with heads elevated. DESIGN: A prospective study. PROCEDURE: Six
      horses were transported by road for 12 h. Clinical and haematological
      examination, transtracheal aspiration and cell function studies were conducted
      before and after transportation. Results obtained after transportation were
      compared to pre-transportation values. RESULTS: After transportation, peripheral
      blood leucocyte and neutrophil numbers were increased and rectal temperatures
      were evaluated. Transtracheal aspirates showed an accumulation of purulent
      respiratory tract secretions with increased numbers of bacteria, particularly
      beta-haemolytic Streptococcus spp and members of the Pasteurellaceae family.
      Three horses also had increased numbers of bacteria from the Enterobacteriaceae
      family relative to corresponding samples from earlier studies. Phagocytosis by
      peripheral blood neutrophils was significantly reduced, while the oxidative burst
      activity of peripheral blood leucocytes was either unchanged or enhanced.
      CLINICAL IMPLICATIONS: Bacterial contamination of the lower respiratory tract
      occurs as a routine consequence of transportation of horses and is likely to be
      an important determinant in the development of transport-associated respiratory
      disease. Inflammatory airway secretions and increased numbers of bacteria were
      rapidly cleared, without clinical evidence of significant pulmonary disease and
      without additional treatment, in normal horses that were allowed to lower their
      heads after transportation. Peripheral blood neutrophilia and a reduction in
      neutrophil phagocytic function were evident for at least 36 h after
      transportation, suggesting that horses may require a number of days to recover
      from the stress of transportation. As the potential role of bacteria from the
      Enterobacteriaceae family in the development of transport-associated respiratory
      disease has not been elucidated, horses which develop clinical disease following
      transportation should undergo thorough bacteriological investigation to ensure
      appropriate treatment.

PMID- 9247696
TI  - Pharmacokinetics of cephalexin in cats after oral administration of the
      antibiotic in tablet and paste preparations.
AB  - OBJECTIVE: To determine the bioequivalence of a paste formulation of cephalexin
      with that of the tablet form. DESIGN: A two-way cross-over study. ANIMALS: Ten
      adult cats of mixed breed. PROCEDURE: The cats, randomly allocated to two groups,
      received either the paste preparation or the tablet orally at 12-hour intervals
      for 48 h before a 12-hour blood collection period. Two weeks later the treatments
      were reversed and the blood sampling repeated. The serum concentrations of the
      antibiotic were determined. The pharmacokinetic factors were analysed using a
      computer. RESULTS: There were no significant differences between the peak
      concentration of cephalexin, or the other pharmacokinetic factors obtained from
      the tablet and paste formulations. The serum profiles of cephalexin following
      four 12-hourly doses of each formulation were similar with the peak serum values
      occurring at approximately 2 h after administration. CONCLUSION: The paste
      formulation and the tablet form are bioequivalent.

PMID- 9247698
TI  - Idiopathic intranuclear inclusion bodies in the renal epithelium of macropods.

PMID- 9247697
TI  - Absorption by sheep of dieldrin from contaminated soil.
AB  - OBJECTIVE: To study the accumulation of dieldrin residues in sheep from ingestion
      of contaminated soils was studied in two experiments. DESIGN: A controlled
      feeding study of sheep fed contaminated soils of different type at varying
      intervals. ANIMALS AND PROCEDURE: Thirty-four 2-year-old wethers were divided
      into four groups (one control sheep only) and fed water-soluble dieldrin or soil
      contaminated with aldrin and dieldrin at varying intervals in the first study. In
      a second study 34 similar sheep were divided into four treatments with one being
      a control. Sheep were fed sandy, high clay or high organic matter soils with
      similar dieldrin and aldrin concentrations. RESULTS: In the first study the
      concentration of dieldrin in the body fat of sheep dosed with dieldrin
      contaminated soil was about half that in the body fat of sheep dosed with an
      equivalent amount of water-soluble dieldrin. The concentration of dieldrin was
      almost the same in sheep fed 500 micrograms of total dieldrin per day as it was
      in sheep fed 5000 micrograms every tenth day, over a 50-day period. In the second
      experiment sheep accumulated nearly three times as much pesticide from a soil
      with a high organic matter content, and about four times as much from a soil with
      a high clay content, as from a sandy soil with the same dieldrin content, over a
      100-day period. The half-life of dieldrin in the fat of all sheep varied between
      96 and 116 days after sheep caused ingesting contaminated soil. CONCLUSIONS:
      Dieldrin concentrations in the fat of sheep that consume dieldrin contaminated
      soil fall within 10 days of removal from the source of contamination. However,
      dieldrin accumulates in the wool of sheep that consume dieldrin contaminated
      soil.

PMID- 9247699
TI  - Adverse reactions in wild, free-ranging European rabbits vaccinated against
      rabbit haemorrhagic virus.

PMID- 9247700
TI  - Tail docking in dogs.

PMID- 9247701
TI  - Preincubation of thymocytes with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      dihydrochloride (H-7) induces apoptosis in non-stimulated thymocytes.
AB  - 1-(5-Isoquinolinesulfonyl1)-2-methylpiperazine hydrochloride (H-7), an inhibitor
      of protein kinases, has been shown to inhibit the thymocyte apoptosis induced by
      various apoptogenic agents. In the present study, when mouse thymocytes were
      pretreated with H-7, washed, and cultured for an additional time, apoptosis was
      induced depending on the preincubation time and the dose of H-7. The protein
      kinase C activity in the H-7-pretreated and -washed cells was not altered,
      suggesting that an alteration of a certain PKC isoform is related to both the
      triggering and the progression of apoptosis.

PMID- 9247702
TI  - Purification, characterization, and expression of rat epididymal beta-D
      galactosidase.
AB  - The purpose of the present study is to purify, kinetically characterize and
      measure the amount of soluble acid beta-D-galactosidase (EC 3.2.1.23) in
      different anatomical regions (caput, corpus, and cauda) of the adult rat
      epididymis. Based upon SDS-PAGE analysis, the subunit molecular mass of the caput
      and cauda enzyme is approximately 85,000 daltons while the corpus enzyme is
      approximately 50,000 daltons. The apparent Km and Vmax values are 67, 24, and 59
      microM and 5.0, 1.88 and 6.3 microM/min./-mg protein for the enzyme purified from
      the caput, corpus, and cauda regions of the epididymis, respectively. However, no
      regional differences in the amount of soluble enzyme protein are observed. These
      data demonstrates regional differences in the activity of epididymal acid beta-D
      galactosidase and suggest that the observed regional differences in enzyme
      activity may be due to posttranslational modifications.

PMID- 9247703
TI  - Cloning, sequence, and expression of a blood group B active recombinant alpha-D
      galactosidase from pinto bean (Phaseolus vulgaris).
AB  - A cDNA encoding pinto bean alpha-D-galactosidase [E.C. 3.2.1.22] was obtained by
      amplification of cDNA using highly conserved sequences found in eucaryotic alpha
      D-galactosidases. Subsequently a full length Phaseolus cDNA clone was obtained
      that is 1537 nt long and contains untranslated 5' and 3' sequences. The
      nucleotide sequence of the cDNA has a high degree of homology with other
      eucaryotic alpha-D-galactosidase genes. The recombinant alpha-D-galactosidase
      (rGal) was expressed in Escherichia coli and purified by ion exchange and
      affinity chromatography. Purified rGal was homogeneous by SDS-PAGE and had
      relative masses of 40.1 and 45.4 kDa under nonreducing and reducing conditions,
      respectively. The N-terminal sequence of the expressed protein contained the
      sequence GNGLGQTPPMG corresponding to that deduced from the cDNA sequence. The
      native molecular weight for rGal was determined to be 32.18 kDa by Sephacryl S
      200 chromatography. The specific activity of the rGal was 349 mu moles of PNP
      alpha-D-galactopyranoside hydrolyzed per mg of pure rGal per min. rGal was highly
      specific for alpha-D-galactosyl residues and degraded B oligosaccharide. No
      detectable hemagglutinin or protease activity was present in the preparations.
      Furthermore, rGal was active against the blood group B antigen on native human
      erythrocytes in cell suspension assays. The only detectable RBC phenotypic change
      was loss of the B and P1 epitopes. Recombinant Phaseolus vulgaris alpha-D
      galactosidase may have useful biotechnical applications in the potential mass
      production of enzymatically converted, universally transfusable type O RBCs.
      alpha-D-galactosidase [E.C. 3.2.1.22] has been purified from a variety of
      procaryotic and eucaryotic species. Most alpha-D-galactosidases have similar low
      molecular weight substrate specificities, but activity against high molecular
      weight substrates is variable. Terminal alpha-D-galactoside residues are present
      in glycoproteins and glycolipids. Some alpha-D-galactosidases have activity
      against alpha-D-galactosyl residues on cell membrane glycoconjugates.
      Glycosidases with this property are useful for carbohydrate structural studies
      and biotechnical applications. Enzymes free of other glycosidase activities with
      activity near neutral pH are particularly useful for membrane modification
      studies on native cells. Complex sugar chains in glycolipids and glycoproteins
      have often been implicated in the growth and development of eucaryotes. In
      particular, complex sugar chains play an important role in the recognition of
      self in the immune system. Some alpha-D-galactosidases can modify certain
      carbohydrate membrane epitopes, thereby modulating the immune response. For
      example, the blood group B epitope expressed on erythrocytes contains a terminal
      alpha-D-galactosyl residue. Individuals lacking this antigen produce naturally
      occurring complement fixing antibodies to the B epitope. Hydrolysis of this
      terminal saccharide destroys the antigenic activity of the B determinant
      producing H antigen (blood type O) on erythrocytes. Only rare individuals produce
      clinically significant antibodies to the H antigen, and therefore, type O red
      blood cells are "universally" compatible and in great demand. Dhar purified alpha
      D-galactosidase isozymes from Phaseolus vulgaris and characterized their
      activity. To our knowledge, our laboratory, in a brief report, is the first to
      describe the cloning of the gene and the use of recombinant enzyme for
      seroconverting blood type B to O cells. This paper describes the cloning,
      sequence, expression, purification, and characterization of recombinant alpha-D
      galactosidase. Activity of the recombinant enzyme on the native human erythrocyte
      blood group B epitope is shown.

PMID- 9247704
TI  - Human placenta cytidine deaminase: a zinc metalloprotein.
AB  - Cytidine deaminase, a tetrameric enzyme purified from human placenta, was shown
      to contain a single atom of tightly bound zinc per subunit by Inductively Coupled
      Plasma Optical Emission Spectrometry analysis. The metal appears to be involved
      in catalysis, as suggested by the inhibition exerted by 1,10-phenanthroline and
      dipicolinic acid. This hypothesis is further supported by the finding that the
      presence of substrate protects the enzymatic activity from dipicolinic acid
      inhibition. Furthermore the total cysteine residues per subunit were investigated
      by sulphydryl groups titrating agents.

PMID- 9247705
TI  - Human placenta cytidine deaminase: proton-linked enzyme activity and substrate
      binding.
AB  - In this work we focused our attention on some catalytic site requirements for
      human placenta cytidine deaminase (CDA). The effect of pH on substrate binding
      and catalysis was studied between pH 3.0 and pH 11.0. The results could be
      discussed postulating the presence of two classes of ionizable groups in the
      active site of CDA. The kinetic parameters pH-dependence has been discussed
      considering the presence of four zinc atoms per each enzyme tetramer. Furthermore
      fluorescence studies on the enzyme and on enzyme-inhibitor complexes, examined by
      using polar and non polar quenchers, allowed to define the substrate(inhibitor)
      dependent accessibility of the tryptophan-containing pocket on each CDA monomer.

PMID- 9247706
TI  - Synergistic stimulation of fibrinogen gelation by casein kinase II and
      polycationic compounds.
AB  - The processes of thrombin-induced gelation of the fibrinogen may be influenced by
      a variety of factors including phosphorylational state of the fibrinogen. Casein
      kinase II (CKII) has been shown to phosphorylate fibrinogen in vitro and
      accelerate gelation of the fibrinogen. In this work, we have demonstrated that
      CKII and polycationic compounds such as polylysine, spermine, and spermidine
      synergistically stimulate thrombin-induced gelation of the fibrinogen. These
      polycationic compounds were also found to increase the stimulatory effects of
      CKII on the platelet aggregation. Current findings suggest potential role of CKII
      and polycationic compounds in the process of hemostasis.

PMID- 9247707
TI  - Expression of bone morphogenetic proteins of human neoplastic epithelial cells.
AB  - Bone morphogenetic proteins (BMPs) are crucial factors of osteogenesis. We
      investigated the expressions of BMP subtypes in human salivary adenocarcinoma
      cell line (HSG-S8), tongue squamous cell (HSC-4) and gingival squamous cell (Ca9
      22) carcinoma cell lines, gastric poorly differentiated adenocarcinoma cell
      (MNK45) and signet ring cell (KATOIII) carcinoma cell lines, rectal
      adenocarcinoma (RCM-1, RCM-2, and RCM-3), and thyroid (8505C) and bladder (T24)
      carcinoma cell lines by reverse transcription-polymerase chain reaction (RT-PCR).
      RT-PCR disclosed that BMP-1 was expressed in all cell lines examined, and BMP-2
      was amplified in almost all cells except MKN45. Two squamous cell carcinomas, HSC
      4 and Ca9-22, and KATOIII expressed only BMP-1 and BMP-2. MKN45 did not express
      BMP-2, but expressed BMP-7 and weakly BMP-4 and BMP-5. In addition to the
      expression BMP-7, and HSG-S8 expressed BMP-6. These findings indicated that the
      neoplastic epithelial cells possessed a rather great potency to express BMP
      mRNAs. On the other hand, among these carcinoma cells, HSG-S8 solely induced bone
      in nude mouse tumors, and HSC-4 and KATOIII contained many calcified masses in
      tumors while the rest did not induce either.

PMID- 9247708
TI  - Interactions of aldolase and glyceraldehyde-3-phosphate dehydrogenase: molecular
      mass studies.
AB  - A gel penetration technique, that measures the dilution undergone by protein
      equilibrium on a short tightly packed gel column, has been employed to determine
      the molecular masses of aldolase (160 kDa), glyceraldehyde-3-phosphate
      dehydrogenase (GPDH; 145 kDa) in the absence and presence of each other and of
      other proteins. The dilution factor (concentration of protein
      applied/concentration of protein after equilibration) was found to be inversely
      related to the molecular mass of the protein. In equimolar mixtures of aldolase
      and GPDH, 0.5-2.5 microM each, the two enzymes exhibited a common molecular mass
      value of 309-316 kDa. These enzymes did not undergo any self association or
      disassociation in this concentration range. Moreover, their molecular masses were
      unaffected by the presence of other proteins tested. When the concentration of
      one of these enzymes (aldolase or GPDH) was held constant and that of the other
      varied, the dilution factor of the former was decreased as the concentration of
      the latter was increased until it corresponded to a molecular mass of ca. 310 kDa
      at equimolar concentrations of the two enzymes. Further increase in the
      concentration of the variable enzyme had no effect. It has been suggested that
      aldolase and GPDH form a 1:1 complex of dissociation constant equal to or less
      than 5 x 10(-8) M. The complex was found to dissociate in the presence of KCl,
      (NH4)2SO4, ATP and NADH whereas its formation was favoured by fructose-1,6
      bisphosphate, glyceraldehyde-3-phosphate, NAD+, ADP, AMP and phosphate ions.

PMID- 9247709
TI  - Unfolding and inactivation of Penaeus penicillatus acid phosphatase during
      denaturation by guanidine hydrochloride.
AB  - The conformational changes of penaeus penicillatus acid phosphatase during
      denaturation in guanidine hydrochloride solutions were studied by following
      changes in the intrinsic fluorescence, ultraviolet difference absorption, and
      circular dichroism spectra. Inactivation of the enzyme in guanidine hydrochloride
      solutions were compared with unfolding of the enzyme molecule. The results show
      that the extent of unfolding in guanidine solutions measured by several different
      methods closely coincide with each other and that slightly lower concentrations
      of guanidine are required to bring about inactivation than are required to
      produce significant conformational changes of the enzyme molecule. At the same
      concentrations, the inactivation rate constants are markedly faster than the rate
      constants for unfolding of the enzyme. The above results suggest that the active
      sites of this enzyme display more conformational flexibility than the enzyme
      molecule as a whole.

PMID- 9247710
TI  - Formation of homo- and heterooligomeric supramolecular structures by D
      glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase in reversed
      micelles of aerosol OT in octane.
AB  - The supramolecular structure of oligomeric enzymes can be specifically regulated
      by changing the size of an inner cavity of Aerosol OT reversed micelles in
      octane. Both D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate
      dehydrogenase (LDH) reveal an ability to exist and function in monomeric, dimeric
      and tetrameric forms (homooligomers). Various heterooligomeric complexes, in
      particular, GAPDH monomer--LDH monomer, GAPDH dimer--LDH tetramer were detected
      in reversed micelles.

PMID- 9247711
TI  - Regulation of androgen receptor (AR) and prostate specific antigen (PSA)
      expression in the androgen-responsive human prostate LNCaP cells by ethanolic
      extracts of the Chinese herbal preparation, PC-SPES.
AB  - As part of the study on the potential use of natural product-based combination
      therapy for treating prostate cancer, we have investigated the effects of a "HPLC
      standardized" herbal preparation, PC-SPES, on the prostate LNCaP cell line.
      Proliferation of the LNCaP cells was inhibited by a 4-6 day incubation with
      ethanolic extracts of PC-SPES. Decrease of cell growth was accompanied by a 60
      70% down-regulation of the proliferating cell nuclear antigen (PCNA) and level of
      secreted PSA. A smaller and more variable decrease (20-40%) in the level of
      intracellular PSA was also observed. The PC-SPES-modulated PSA changes occurred
      concurrently with the decrease of AR expression, based on Western blot analysis
      and binding to the radioactive ligand [3H]R1881. A 60% decrease in R1881 binding
      occurred after a 24 h incubation with PC-SPES. These results suggest that PC-SPES
      negatively affects cell growth in part through its ability to modulate changes in
      PCNA, and may decrease PSA levels indirectly by suppressing AR expression.

PMID- 9247712
TI  - Helicobacter pylori lipopolysaccharide inhibition of gastric somatostatin
      receptor: effect of sucralfate.
AB  - In this study, we investigated the inhibitory effect of Helicobacter pylori
      lipopolysaccharide on the binding of somatostatin to gastric epithelial cell
      membrane receptor, and assessed the effect of antiulcer agent, sucralfate, on
      this process. The assays conducted with the somatostatin receptor, purified from
      the solubilized epithelial cell membranes by affinity chromatography on Affi-Gel
      [D-Tryp8]SRIF-14, revealed a dose-dependent inhibition in receptor-somatostatin
      binding by the lipopolysaccharide which reached a maximum of 94.1%. This effect
      of H. pylori lipopolysaccharide was countered by sucralfate that produced a 92.5%
      restoration in receptor-somatostatin binding at 70 micrograms/ml of the drug. The
      findings demonstrate that sucralfate is capable of reversing the interference by
      H. pylori lipopolysaccharide with somatostatin-receptor binding on gastric
      mucosal G-cells.

PMID- 9247713
TI  - The control of oxygen affinity in the three human embryonic haemoglobins by
      respiration linked metabolites.
AB  - The effect of CO2, ATP and lactate ions on the oxygen affinity of the three human
      embryonic haemoglobins have been studied. CO2 lowers the affinity of both the
      adult and embryonic haemoglobins for oxygen, as does ATP. The ATP effect follows
      a simple binding process with an equilibrium constant in the mM range. Lactate
      ions have no effect on the oxygen equilibrium process, over the concentration
      range studied. These findings are discussed in terms of the likely physiological
      conditions experienced by human embryonic red blood cells.

PMID- 9247714
TI  - The effect on mitochondrial function of the tRNA Ser(UCN)/COI A7445G mtDNA point
      mutation associated with maternally-inherited sensorineural deafness.
AB  - An A to G point mutation at nucleotide position 7445 in the mitochondrial DNA
      genome is associated with maternally-inherited sensorineural deafness in two
      separate human pedigrees. To determine whether this point mutation
      [tRNA(SER)UCN)/COI A7445G] led to sensorineural deafness by affecting cellular
      energy metabolism we investigated the bioenergetic function of mitochondria in
      lymphoblastoid cultures established from these patients. Even though essentially
      all of the mitochondrial DNA in these cells contained the mutation at nucleotide
      position 7445, there was no effect on a number of mitochondrial bioenergetic
      functions (mitochondrial content, membrane potential in both intact and digitonin
      permeabilised cells, cellular ATP/ADP ratios and respiratory enzyme activity)
      when compared with control cells. The implications of these findings for both the
      aetiology of the sensorineural deafness associated with the A7445G mtDNA
      mutation, and the role of bioenergetic defects in mitochondrial DNA diseases in
      general are discussed.

PMID- 9247715
TI  - The alpha 2 beta 1 integrin binds to the CB4 peptide of the alpha 2(I) collagen
      chain.
AB  - The adhesion of platelets and other cells to type I collagen is mediated by the
      alpha 2 beta 1 integrin. A binding site for the alpha 2 beta 1 integrin within
      the alpha 1(I) collagen chain has previously been localized to the cyanogen
      bromide fragment alpha 1(I)-CB3. We noe show by use of inhibitory monoclonal
      antibodies against the alpha 2 beta 1 integrin, that platelets also adhere to
      purified alpha 2(I) collagen chains by a mechanism mediated by the alpha 2 beta 1
      integrin. Moreover, following isolation of cyanogen bromide fragments of the
      alpha 2(I) collagen chain by HPLC, we demonstrate that alpha 2 beta 1 integrin
      mediated adhesion is restricted to the CB4 fragment of the alpha 2(I) collagen
      polypeptide. These findings indicate the presence of at least two spatially
      distinct binding sites for the alpha 2 beta 1 integrin on the native type I
      collagen triple helix.

PMID- 9247716
TI  - Patterns of expression of Hoxa-11 in micromass cultures of chick limb mesenchyme
      from various stages suggest a role for Hoxa-11 in the specification of the
      zeugopod.
AB  - During chick limb development the expression of Hoxa-11 specifically associated
      with the prospective zeugopod (radius + ulna) region. A series of micromass
      cultures were performed using mesenchyme from whole stage 18/19 or 20/21 limbs or
      mesenchyme from the tips of stage 22/23, 23/24 or 25 limbs. In such cultures,
      limb mesenchyme undergoes chondrogenesis paralleling its fate in vivo. Hoxa-11
      and collagen type II mRNA were examined by dot blot and in situ analysis at
      different time points. The highest level of Hoxa-11 mRNA was found in micromass
      cultures of the tips of stage 22/23 and 23/24 limbs at 48 hours. Between stages
      22 and 24, the determining events occur which subsequently lead to the formation
      of the zeugopod by the mesenchyme present in the tips at these stages. This
      correlation further supports a possible role of Hoxa-11 in the specification of
      the zeugopod.

PMID- 9247717
TI  - Autolytic activation mechanism of Bombyx acid cysteine protease (BCP).
AB  - Acid cysteine proteinase in the eggs of the silkmoth, Bombyx mori, exists as an
      inactive proenzyme. This 47-kDa pro-BCP1 zymogen molecule can be processed in
      vitro into an enzymatically active 39-kDa BCP molecule. In this current study,
      the maximum rate of processing in vitro was achieved at approximately pH 4.0, at
      a temperature of 37 degrees C under reducing conditions. The rate of conversion
      was not affected by increasing concentrations of pro-BCP. We prepared immobilized
      BCP bound to AH-Sepharose and examined the activation. Immobilized pro-BCP was
      autolysed, although the rate of processing was slow, indicating that the reaction
      might be an intramolecular one. Kinetic experiments suggest that the mechanism is
      likely to involve a stepwise reaction, in which pro-BCP is converted to an active
      enzyme through intermediate forms releasing small peptides stepwise. The results
      suggest that autocatalytic cleavage (intramolecular) is a major processing step
      in the early stage of pro-BCP activation.

PMID- 9247718
TI  - No influence of a single bout of exercise on urinary excretion of 8-hydroxy
      deoxyguanosine in humans.
AB  - We investigated the effect of a single bout of intensive exercise on the
      excretion of 8-hydroxy-deoxyguanosine in the 24 h urine from healthy non-smokers.
      We studied three exercise tests in Experiment 1; which consisted of incremental
      exercise to exhaustion on a treadmill in eleven male long distance runners.
      Experiment 2; which comprised incremental exercise until reaching exhaustion on a
      bicycle ergometer in six male untrained subjects. Experiment 3; which consisted
      of a 20 km run by eleven male long distance runners. No differences in the
      urinary 8-hydroxy-deoxyguanosine excretion were observed from days 1 to 3 after
      each respective exercise regimen. However, significant increases in the plasma
      creatine kinase activity were observed at 24 h or 48 h after exercise, except for
      Experiment 2. Our results thus suggest that the oxidative stress during a single
      bout of intensive exercise does not result in an accumulation of oxidative DNA
      damage.

PMID- 9247719
TI  - Heat-treated myosin does not bind ATPase--inhibiting antibodies.
AB  - Polyclonal antibodies to native chicken pectoral fast-twitch myosin are directed
      to all subfragments of the molecule (S1, S2 and LMM), as seen in the ELISA and
      Western blotting techniques. The antibodies inhibit the Ca(2+)-activated myosin
      ATPase. Absorption of the antibodies with native myosin abolishes these
      reactions. Heat treatment of myosin for 2h at 40 degrees C will inactivate myosin
      ATPase and alter its antibody binding pattern: the binding of antibodies to the
      rod fractions is reduced, that to the globular head (S1) completely abolished.
      Thus, these antibodies are useful as sensitive probes for the structural
      integrity of the myosin head.

PMID- 9247720
TI  - High level expression of recombinant plasminogen activator inhibitor-1 in
      Escherichia coli and generation of its mutants involving Asp125, Glu128 and
      Glu130.
AB  - Plasminogen activator inhibitor-1 (PAI-1) cDNA was expressed in Escherichia coli
      (E. coli) with high efficiency using a heat-inducible vector. About 100 mg of
      recombinant PAI-1 (rPAI-1) could be obtained from 1 liter of bacteria culture.
      rPAI-1 in inclusion bodies was purified by pI precipitation and Sephadex G-75
      chromatography. After treatment with 4 mol/L guanidinium chloride and dialysis,
      the largely inactive PAI-1 gained considerably in activity as judged by its
      reaction with low molecular weight u-PA (LMW-u-PA). Degenerated oligonucleotides
      containing ApaI site and mutations at Asp125, Glu128, Glu130 in PAI-1 cDNA were
      synthesized. To facilitate the introduction of mutations, an ApaI site was first
      generated in PAI-1 cDNA using one of the oligonucleotides. Taking advantage of
      the APaI site, thirteen PAI-1 mutants involving Asp125, Glu128 and Glu130 were
      produced with these oligonucleotides using PCR. Most of the PAI-1 mutants had a
      similar activity as compared to wild type PAI-1, while some of the triple-site
      mutants had completely lost their activity.

PMID- 9247721
TI  - Thermal denaturation of glutathione reductase from cyanobacterium Spirulina
      maxima.
AB  - The thermal unfolding of glutathione reductase (NAD[P]H:GSSG oxidoreductase EC
      1.6.4.2.) from cyanobacterium Spirulina maxima was monitored by differential
      scanning calorimetry and circular dichroism at neutral pH. Covalent cross-linking
      of enzyme at different temperatures revealed dimer as the species undergoing the
      thermal transition. A single endotherm was observed, but its thermodynamic
      parameters showed dependence on the scan rate. In the transition zone,
      aggregation of the dimeric species was observed. Analysis of the enzyme heated at
      80 degrees C revealed that the resultant species retained a high content of
      secondary structure. The addition of low concentrations of guanidinium
      hydrochloride resulted in a full cooperative thermal transition. A model in which
      the dimeric protein undergoes a partial unfolding in a kinetically controlled
      fashion is proposed, such that the experimental value of delta H(cal) results
      from the simultaneous occurrence of endothermic and exothermic events.

PMID- 9247722
TI  - Synthesis and imaging of blood-brain-barrier permeable nitroxyl-probes for free
      radical reactions in brain of living mice.
AB  - Three different lipophilic nitroxyl-probes having capability to pass the blood
      brain barrier were, for the first time, synthesized to estimate free radical
      reactions in brain of living animals. Two of the three were designed to be
      hydrolyzed by esterase and remain in cell. All 3 probes had high n-octanol/buffer
      partition coefficients and gave 2 signal components in in vivo ESR spectra at
      head of living mice after intravenous injection. The ESR parameters of 2
      components agreed with those of probes dissolved in water and lipidic phases. ESR
      CT imaging on the nitroxyl-proves after intravenous injection revealed that all
      probes presented in both encephalon and extracranial region of head. Tissue
      distribution of the nitroxyl-probes demonstrated that the newly synthesized
      lipophilic nitroxyl-probes had capability to pass the blood-brain barrier and
      accumulated in brain than that of hydrophilic probe.

PMID- 9247723
TI  - Urine glycosaminoglycan concentrations in mucopolysaccharidosis VI-affected cats
      following bone marrow transplantation or leukocyte infusion.
AB  - Urinary glycosaminoglycan (GAG) concentrations were determined in nineteen normal
      cats (eleven kittens and eight adult cats), eighteen mucopolysaccharidosis VI
      (MPS VI)-affected untreated cats (ten kittens and eight adult cats), thirteen
      cats MPS VI-affected cats following bone marrow transplants (BMT), and two MPS VI
      affected cats following intravenous infusion of leukocytes from normal cats.
      Mucopolysaccharidosis VI-affected cats treated with BMT had a precipitous
      decrease in urinary GAG by day 7 post-BMT, then a transient increase just prior
      to engraftment, followed by a sustained decrease to within, or near, the range of
      urinary GAG concentration established for normal cats. The pre-engraftment
      changes in urinary GAG excretion were reproduced by leukocyte infusion. After
      infusion of comparable members of normal peripheral blood leukocytes, a
      significant decrease in urinary GAG concentrations, specifically dermatan sulfate
      (DS), was seen with a nadir at day 5 post-infusion, followed by a return by day 9
      to pre-infusion values. Post-engraftment, a continued low urinary GAG
      concentration with a specific decrease in DS can be utilized to document
      successful autologous engraftment in MPS VI-affected cats.

PMID- 9247725
TI  - Diagnosis of a deletion of steroid sulfatase by polymerase chain reaction and
      high-performance liquid chromatography.
AB  - X-linked ichthyosis is an inherited skin disorder caused by deficiency of steroid
      sulfatase activity. We studied the possibility of diagnosing the defect in
      patients and carriers by using polymerase chain reaction (PCR) and high
      performance liquid chromatography (HPLC). We chose the usual PCR procedure of 25
      temperature cycles. PCR products were resolved by HPLC and quantified by
      measurement of absorbance at 260 nm. The optimal amount of DNA template was 50 ng
      using either steroid sulfatase (STS) or beta-globin (internal control) primer.
      The results show that the amount of STS in ichthyosis patients was null. The
      amount of STS DNA in mothers of patients was half of that in normal females. By
      this HPLC-PCR method we will able to diagnose not only ichthyosis patients but
      also carriers before birth.

PMID- 9247724
TI  - Recombinant human TSH receptor expressed in E. coli.
AB  - We expressed the extracellular domain (20-408 aa, (T) of human TSH receptor
      (TSHR) in E. coli to detect TSHR autoantibodies (TRAb) and, moreover, we
      expressed the two portions (20-218 aa (5') and 217-408 aa (3')) of the
      extracellular domain thought to distinguish thyroid stimulating antibodies (TSAb)
      from blocking antibodies (TSBAb), using pGEX.3X as the expression vector. Using
      Western blotting analysis of the sera from patients with autoimmune thyroid
      disease, sera from Graves' patients and patients with idiopathic myxedema who had
      TSBAb reacted with the fusion protein (T), but none of the control sera reacted
      with it. We further evaluated whether or not the positive sear for T recognized
      fusion proteins (5') or (3'). The sera from Graves' patients reacted with both
      fusion proteins (5') and (3'). The sera from patients with idiopathic myxedema
      did not react with either of fusion proteins (5') or (3'). These findings suggest
      that these recombinant TSHR proteins could be used as antigens to detect TRAb,
      and differentiate TSABb from patients with idiopathic myxedema.

PMID- 9247726
TI  - Newborn genetic identification: a protocol using microsatellite DNA as an
      alternative to footprinting.
AB  - Newborn identification by foot- or finger-printing presents serious drawbacks.
      This study proposes an alternative method based on DNA analysis of blood-spots
      taken from the newborn child. CSF1PO, TPOX and TH01 microsatellite loci were
      chosen to develop a fast and reliable protocol to be applied in cases where it is
      suspected that newborn children have been exchanged. The advantage of these loci
      is that one can simultaneously amplify them by PCR multiplex reaction and
      determine their alleles, thereby reducing the time needed for identification
      tests. Moreover, the amplification products of these loci are very small (< 350
      bp) and so can be analyzed in samples with degraded DNA. We have been able to
      prove that it is possible to obtain results in blood-spots taken from newborns up
      to 13 years before and kept at room temperature. Thus the protocol proposed here
      can be applied in long-term post-natal identification cases.

PMID- 9247727
TI  - Simple test to evaluate the risk of urinary calcium stone formation.
AB  - A simple test to evaluate the capacity of a urine to crystallize calcium salts is
      presented. The test is based on the fact that if a non-protected non-renewed
      surface remains in contact with a urine, sooner or later the contained
      supersaturated substances crystallize on it. Thus, by using an adequate surface,
      it is possible to derive a period within which a normal urine does not
      crystallize whereas a lithogenic urine induces the growth of calcium salts. The
      test was applied to urines of oxalocalcic stone-formers and healthy people and
      showed an excellent discrimination between clearly abnormal and healthy urines.
      Semiologic analysis of the data is also included.

PMID- 9247728
TI  - Study of apoB gene signal peptide insertion/deletion polymorphism in a healthy
      Serbian population: no association with serum lipid levels.
AB  - The apolipoprotein B (apoB) signal peptide polymorphism was studied in unrelated
      healthy individuals. A total of 232 women and 222 men were analyzed separately.
      The relative frequencies of Del allele in women and men were 0.42 and 0.37,
      respectively. More heterozygous individuals were detected in comparison with
      other populations, using a modified silver staining method on polyacrylamide gel
      for visualization of Ins and Del alleles. There was no statistically significant
      difference in mean lipid levels adjusted for age, BMI, smoking habit and blood
      pressure between the three Ins/Del genotypes in both samples (ANOVA). Therefore,
      no differences were shown in the genotype frequency distribution throughout the
      lipid quartiles.

PMID- 9247730
TI  - Mitochondrial aspartate aminotransferase isoenzyme: a biochemical marker for the
      clinical management of alcoholics?
AB  - Serum mitochondrial and total aspartate aminotransferase activity was quantified
      by a characterized immunochemical method in 126 subjects, 44 healthy controls and
      82 chronic alcoholics (51 outpatients and 31 monitored through 15 days). The
      monitored alcoholics were divided into actual abstinents (n = 21) and drinkers (n
      = 10) by blood ethanol concentration performed daily. The aims of the present
      study were: (a) to compare the diagnostic diagnostic usefulness of the
      mitochondrial isoenzyme and the mitochondrial/total aspartate aminotransferase
      ratio to detect problematic drinkers; (b) to evaluate the suitability of these
      indices to monitor abstinence, a difficulty not yet solved in the clinical
      management of alcoholics. The results demonstrated the mitochondrial isoenzyme to
      be more suitable to discriminate between controls and alcoholics (Kruskal and
      Wallis ANOVA, Bonferroni test, P < 10(-5) and mostly between actual drinkers and
      other alcoholics (P < 0.041). So acute alcohol consumption may be a significant,
      suggestive and until now inadequately examined factor in evaluating the
      suitability of mAST as a marker. The results, showing that mAST peaks quickly
      appear in the presence of a new alcohol intake, should indicate mAST as a
      possible marker of acute alcohol intake useful in checking self-claimed
      abstinence.

PMID- 9247731
TI  - Long-term follow up of ionic plasma fluoride level in patients receiving
      hemodialysis treatment.
AB  - The elimination half-life of fluoride is significantly increased in patients with
      chronic renal failure. This led us to conduct a study of variations of its plasma
      levels in 35 patients receiving dialysis treatment. In this population, there is
      a gaussian distribution of the values before and after the hemodialysis session,
      with a significant decrease in the averages. Furthermore, there is a highly
      significant correlation between fluoride levels before and after the dialysis
      session (P < 0.00001), and also between the amount of time in hemodialysis (in
      months) and the average fluoride level before dialysis (r = 0.624; P = 0.008).
      The presence of a group of patients consuming fluoride waters such as Vichy St
      Yorre Water was easily identified by their excessive fluoride levels (above 100
      micrograms/l), which could have a tendency to increase the risks of this group.

PMID- 9247729
TI  - The effect of Simvastatin on the plasma antioxidant concentrations in patients
      with hypercholesterolaemia.
AB  - The aim of this study was to monitor the antioxidant status of patients with
      hypercholesterolaemia during treatment with Simvastatin. Forty-seven patients, of
      whom 25 had confirmed familial hypercholesterolaemia (FH), were treated with 10
      or 20 mg of Simvastatin per day for 14 weeks. As expected, total cholesterol and
      LDL cholesterol concentrations decreased considerably, while HDL cholesterol
      concentrations increased during drug treatment. In neither FH nor non-FH patients
      were any significant changes observed for retinol status, while plasma vitamin C
      concentrations were also not adversely affected by the drug therapy. In both
      patient groups Simvastatin therapy led to a significant decrease in plasma alpha
      tocopherol (P < 0.05) concentrations, however, the alpha-tocopherol/total
      cholesterol ratio increased by 9.1 (P < 0.01) and 12.1% (P < 0.01) in FH and non
      FH patients, respectively, during the 14-week treatment period. The coenzyme
      Q10/total cholesterol ratio did not change significantly in non-FH patients, but
      was significantly lower (P < 0.05) than the baseline ratio after 4 and 14 weeks
      of Simvastatin treatment in FH patients. The alpha-tocopherol/total cholesterol
      ratio of FH patients remained consistently and significantly lower (P < 0.01)
      compared with non-FH patients, indicating that LDL from the former group may be
      more vulnerable to free radical-mediated damage and lipid peroxidation. Our
      results suggest that the significant decline in circulating alpha-tocopherol and
      coenzyme Q10 concentrations was mainly a function of the decrease in serum total
      cholesterol concentrations.

PMID- 9247732
TI  - Minimal illegitimate levels of cytokeratin K19 expression in mononucleated blood
      cells detected by a reverse transcription PCR method (RT-PCR).
AB  - Cytokeratin K19 (CK19) expression was evaluated by a reverse transcription PCR
      method (RT-PCR) in the RNA obtained from peripheral blood stem cell collections
      (PBSC) from four patients with breast cancers (BC) and 34 mononucleated blood
      cell (MBC) negative controls (17 PBMC from normal subjects 12 PBSC from different
      types of leukaemias--M3, M4Eo, M2, etc.--and two from patients with Hodgkin's
      lymphoma; and three bone marrow (BM) collections). Two BC tissues were taken as
      positive controls. The method studied (Datta YH, Paul T, Adams PT, Drobyski WR.
      Sensitive detection of occult breast cancer by reverse transcription polymerase
      chain reaction. J Oncol 1994;12:475-8) is sensitive enough to allow the detection
      of CK19 transcripts in a 10(-6) dilution of cDNA reverse transcribed from 1
      microgram of BC RNA, but CK19 transcripts were also detected in 64% of the RNA
      obtained from the MBC controls. However, the amplified product detected in the
      control samples represents the transcript of the CK19 gene as confirmed by the
      results of Mae III digestion. It should be pointed out that although the CK19
      expression was detected, the levels of expression in PBMC were almost negligible
      for they disappeared at 1:5 cDNA dilution. Moreover, a direct relationship
      between the number of BC cells added to PBMC and the increasing dilution levels
      of the cDNA necessary to prevent CK19 expression was observed. This allows us to
      conclude that the cDNA dilutions make it possible to distinguish the false from
      the true positive samples and that, in addition, the cDNA dilutions inform about
      the degree of BC cell contamination.

PMID- 9247733
TI  - Activity of class I and II isoenzymes of alcohol dehydrogenase measured by a
      fluorometric method in the sera of patients with obstructive jaundice.
AB  - Using new fluorogenic substrates, we measured the activity of class I and II
      alcohol dehydrogenase (ADH) isoenzymes in the sera of patients with obstructive
      jaundice. The activity of class I isoenzymes was elevated two-fold, whereas that
      of class II isoenzymes was unchanged. This increase of class I isoenzymes
      explains low increase of total serum ADH activity. ADH isoenzymes and total
      enzyme activities correlated better with aminotransferases, than with alkaline
      phosphatase and gamma-glutamyltransferase, but we can conclude that class I ADH
      isoenzymes measured with fluorogenic substrates are indicative of obstructive
      jaundice.

PMID- 9247734
TI  - A novel test for fecal occult blood by the hybridization method with specific
      human deoxyribonucleic acid in leucocytes: preliminary experiment.

PMID- 9247735
TI  - Mutations in the 11 beta-hydroxysteroid dehydrogenase type II enzyme associated
      with hypertension and possibly stillbirth.
AB  - The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts
      cortisol into cortisone, thus preventing occupation of the non-selective
      mineralocorticoid receptor by glucocorticoids in the kidney. Placental 11 beta
      HSD2 is also thought to protect the fetus from the high maternal circulating
      levels of glucocorticoids. Mutations generating inactive enzymes have been
      described in the HSD11B2 gene in the congenital syndrome of apparent
      mineralocorticoid excess (AME)--a low renin form of hypertension. Recently, a
      mutation has been identified in a family with AME and in which there is a high
      incidence of stillbirths. In this study we have expressed the R374X mutation and
      show that the mutant is devoid of enzyme activity in intact mammalian cells
      expressing a significant level of the truncated protein. While this observation
      elucidates the cause of AME in this family the degree to which R374X also
      contributes to the higher incidence of failed pregnancies remains to be
      determined.

PMID- 9247736
TI  - Cardiovascular hypertrophy does not predispose to genetic hypertension.
AB  - It has been proposed that cardiovascular hypertrophy precedes and contributes to
      the development of genetic hypertension. In a genetically segregating population
      we determined whether susceptibility to high blood pressure was associated with
      cardiovascular structural abnormalities in youth. In 9-week old male F2 rats
      derived from a cross of spontaneously hypertensive rats (SHR) and inbred
      normotensive Donryu (DRY) rats we determined left ventricular mass (LVM) by
      echocardiography and the media-lumen ratio (MLR) of mesenteric resistance vessels
      by biopsy. Direct mean arterial pressure was measured in the same rats at 20
      weeks of age. The ranges of LVM and MLR in young F2 rats encompassed values seen
      SHR and DRY at this age. However, no correlation was observed between LVM or MLR
      and subsequent blood pressures at 20 weeks of age. The blood pressure of F2 rats
      with cardiovascular structural phenotypes within the SHR range was no higher than
      the remainder of the F2 population. These studies do not support the hypothesis
      that hypertrophy of the heart or mesenteric resistance vessels confer
      susceptibility to the development of genetic hypertension.

PMID- 9247737
TI  - Regulation of human renin gene transcription by cAMP.
AB  - To delineate the cis-acting elements of the proximal promoter responsible for
      cAMP-induced human renin gene transcription, 5'-flanking regions of the human
      renin gene were fused to a luciferase reporter gene and transfected in chorionic
      cells. Forskolin treatment induced the expression of luciferase by 2.4 fold when
      the reporter plasmid contained the promoter region (-582 to +16). Mutation or
      deletion of the CRE diminished (1.7 fold) but did not abolish cAMP-induced
      transcription, demonstrating that region containing the CRE and region containing
      a Pit-1 site were both necessary for cAMP maximal induction. Taken together,
      these results show that the cAMP response of the human renin gene may involve
      CREB binding the CRE and tissue-specific factors (from chorionic and kidney cell
      origin), different from Pit-1, that interact with the Pit-1 response DNA
      elements.

PMID- 9247738
TI  - Insulin receptor gene in hypertension.
AB  - The first molecular genetic association with human essential hypertension (HT)
      involved the insulin receptor gene (INSR). This highly significant result in
      Caucasians was for an insertion/deletion polymorphism in intron 9. A polymorphism
      in exon 8 showed a weak association, but a microsatellite in intron 2 proved
      negative for HT, although has shown an association with plasma insulin in
      Japanese. A similar spectrum of genetic associations for variants spanning INSR
      has been noted for insulin-dependent diabetic patients with rapidly-progressing
      renal disease, a subgroup having a strong family history of essential HT.
      Association with HT has also been found for an INSR variant in CHinese. Insulin
      resistance secondary to an INSR 'defect', or other causes, would increase
      insulin, which has cardiovascular effects, and insulin can raise angiotensinogen.
      Also, insulin is co-secreted with amylin, which can increase renin secretion. In
      the spontaneously HT rat there is evidence for reduced down-regulation of INSR
      expression in response to NaCl-loading, consistent with a promoter effect. When
      combined with observations of insulin resistance in essential HT patients and
      their pre-HT offspring, the possibility of dys-regulation of INSR merits
      attention in disease etiology in a proportion of essential HT patients.

PMID- 9247739
TI  - Genetics of blood pressure and associated phenotypes in the Lyon rat.
AB  - The Lyon model of genetic hypertension is made of 3 simultaneously selected
      strains, one hypertensive (LH) one normotensive (LN) and one with low blood
      pressure (LL). Since LN and LL rats exhibit the same blood pressure (BP) LH rats
      can be compared to 2 genetically pure and different strains of control animals.
      This proved to be useful for the interpretation of the data of molecular genetic
      studies, eg: since the renin gene was polymorphic between LH and LN but not
      between LH and LL rats it could be suggested that the reported linkage of renin
      gene polymorphism and high BP in F2 hybrids may involve another closely located
      gene. LH rats associate to high BP spontaneous increases in body weight, plasma
      cholesterol, fibrinogen and hematocrit. During the phenotyping of F1 and F2
      hybrids from a LH x LN cross and of back-crosses to LH rats it was observed that
      all these phenotypes were recessive, except the large body weight of LH rats
      which was dominant and, thus, unrelated to BP. On the contrary, BP was
      significantly related to plasma cholesterol in both F2 and back-cross rats and,
      in this latter cohort, plasma cholesterol correlated also with fibrinogen and
      hematocrit levels. Therefore, the study of the Lyon rat may be useful not only to
      determine the genes involved in hypertension but also those which contribute to
      other cardiovascular risk factors such as elevated fibrinogen and hematocrit.

PMID- 9247740
TI  - Central nervous system monoamine neurotransmitter turnover in primary and obesity
      related human hypertension.
AB  - Recent experiments in laboratory animals have challenged the conventional view
      that the dominant effect of CNS noradrenergic neurons in cardiovascular control
      is sympathetic nervous inhibition and blood pressure reduction, describing
      instead sympathetic activation. We have tested whether such a stimulant effect on
      sympathetic outflow is also evident in human hypertension. CNS norepinephrine
      turnover was estimated from the combined overflow of norepinephrine, MHPG and
      DHPG into the internal jugular veins. Cerebral blood flow scans allowed
      differentiation between cortical and subcortical jugular venous drainage. In
      patients with pure autonomic failure, jugular overflow of norepinephrine and
      metabolites was not reduced, indicating brain neurons and not cerebrovascular
      sympathetics was the source. In healthy men, CNS norepinephrine turnover and
      muscle sympathetic nerve activity were directly related (p < 0.02).
      Administration of the ganglion blocker, trimethaphan, caused a compensatory five
      fold increase in jugular overflow of MHPG. Conversely, intravenous clonidine
      reduced CNS norepinephrine turnover by approximately 50%, this possibly
      representing a mechanism of drug action. In cardiac failure patients, sympathetic
      nervous activation was associated with a trebling of CNS norepinephrine turnover
      (p < 0.01). In untreated patients with essential hypertension, the sympathetic
      activation present was associated with 250% higher CNS norepinephrine turnover (p
      < 0.01), but in subcortical brain regions only. A close and direct relation
      exists between brain norepinephrine turnover and human sympathetic nervous
      activity. CNS release of norepinephrine, presumably in the forebrain where
      noradrenergic neurons are sympathoexcitatory and pressor, mediates increased
      sympathetic nerve firing in patients with essential hypertension.

PMID- 9247741
TI  - Central imidazoline receptors and centrally acting anti-hypertensive agents.
AB  - We have examined the location and contribution of imidazoline receptors (IR) in
      mediating the hypotensive and sympatholytic actions of first and second
      generation anti-hypertensive agents in rabbits. We found that the hypotension
      produced by rilmenidine and moxonidine given intravenously (i.v.) or into the
      fourth ventricle (4V) was preferentially reversed by the IR antagonists idazoxan
      and efaroxan (compared to a selective alpha(2)-adrenoceptor antagonist 2-methoxy
      idazoxan), suggesting that IR are important in the sympatho-inhibition produced
      by these agents. Clonidine was not preferentially reversed by the IR antagonists
      suggesting an action via alpha(2)-adrenoceptors. In anaesthetised rabbits, the
      rostral ventrolateral medulla (RVLM) was the most potent site for rilmenidine to
      produce the sympatho-inhibition and modulation of sympathetic baroreflexes. alpha
      Methylnoradrenaline was also sympatholytic suggesting alpha(2)-adrenoceptors are
      also present in this site. Microinjection of the IR and alpha(2)-adrenoceptor
      antagonists showed that rilmenidine activates IR in the RVLM but that alpha(2)
      adrenoceptors are also activated as a consequence. These studies suggest that
      rilmenidine acts primarily via IR in the RVLM to reduce sympathetic tone but also
      imply an important association of alpha(2)-adrenoceptors and IR in the region.

PMID- 9247742
TI  - The supply of vasomotor drive to individual classes of sympathetic neuron.
AB  - The vasoconstrictor supplies to different tissues show distinct patterns of
      ongoing and reflex activity, indicating that they are driven by distinct central
      pathways. Vasomotor tone depends heavily on connections from the brainstem, so
      class-specific vasomotor drives have been sought amongst the sympathetic premotor
      neurons which provide those connections. Premotor neurons of the rostral
      ventrolateral medulla (subretrofacial nucleus) provide most descending vasomotor
      drive. Together, they drive the sympathetic supplies to heart, blood vessels and
      adrenal, but not 'non-cardiovascular' sympathetic responses (sweating, pupil
      dilatation, piloerection, etc.). Individually, they provide preferential or
      selective drives to particular classes of 'cardiovascular' sympathetic outflow.
      Subretrofacial neurons are arranged topographically, forming a neural map of the
      functional class (target tissue), not the body region, of the driven outflows. It
      is still unknown whether other premotor cell groups are organised this way. Nor
      are the premotor pathways to 'non-cardiovascular' sympathetic nerves yet well
      defined.

PMID- 9247743
TI  - Central interactions between noradrenaline and neuropeptide Y in the rat:
      implications for blood pressure control.
AB  - Neuropeptide Y (NPY) and noradrenaline are co-localised in central neurones and
      both transmitters exert cardiovascular effects. Using microdialysis and push-pull
      techniques to measure transmitter release in vivo, and microinjection studies, we
      examined the role(s) of central noradrenaline and NPY in blood pressure
      regulation in the hypothalamus and nucleus tractus solitarius (NTS) of the rat.
      Hypothalamic noradrenaline release was increased following haemorrhage and
      reduced after phenylephrine infusion. Ageing is associated with markedly reduced
      NPY concentrations in the hypothalamus. 18-month old animals showed a reduced
      ability to release both NPY and noradrenaline to a potassium depolarisation
      stimulus. NTS administration of NPY induced dose-dependent decreases in blood
      pressure and heart rate. The depressor but not the bradycardic response was
      attenuated by prior administration of yohimbine. NTS microinjection of 23 pmol
      NPY induced similar cardiovascular effects in spontaneously hypertensive and
      Wistar Kyoto rats. NPY and noradrenaline appear to interact at several sites in
      the brain known to be important for blood pressure control.

PMID- 9247745
TI  - Effect of angiotensin II on striatal dopamine release in the spontaneous
      hypertensive rat.
AB  - We have previously demonstrated that angiotensin II stimulates the release of
      dopamine from the normotensive rat striatum via the AT1 receptor. In this study,
      the effect of angiotensin II-stimulated striatal dopamine release in the
      spontaneous hypertensive rat was compared to normotensive controls. In the
      spontaneous hypertensive rat, angiotensin II stimulated dopamine release to 169
      +/- 13% (P < 0.05) in the experimental period, with levels remaining high in the
      recovery phase, 158 +/- 16% (P < 0.05). This effect was not significantly
      different from the response in normotensive controls, in which angiotensin II
      stimulated dopamine release to 149 +/- 18% (P < 0.05) in the experimental period,
      with the effect also persisting through the recovery period, 244 +/- 62% (P <
      0.05). Thus, despite reports of increased activity of the brain angiotensin II
      and dopamine systems in the spontaneous hypertensive rat, there is no evidence of
      abnormal regulation of the striatonigral dopamine system.

PMID- 9247744
TI  - C-fos expression in central neurons mediating the arterial baroreceptor reflex.
AB  - The immediate early gene c-fos is a transcription regulating factor that is
      widely employed as a marker of neuronal activation. In this study we have used c
      fos expression to identify vasomotor neurons in the brainstem and spinal cord
      that are activated after interventions that alter blood pressure. These neurons
      are likely to be those that subserve the arterial baroreceptor reflex and
      maintain blood pressure within a defined range. With the combination of Fos
      expression and neuronal tracing, we describe the location and central connections
      of these neurons. The differential expression of Fos in neurons in separate
      regions of the brainstem and spinal cord, after either hypotensive or
      hypertensive stimuli in conscious rats, supports current opinion about baroreflex
      circuitry. The central processes of baroafferent neurons synapse with second
      order baroreflex neurons in the nucleus tractus solitarius. From this region
      baroreceptor information is transmitted to neurons in the caudal ventrolateral
      medulla and then to neurons in the rostral ventrolateral medulla. The sympathetic
      preganglionic neurons in the intermediolateral column of the thoracolumbar spinal
      cord are the final crucial site involved in the arterial baroreflex.

PMID- 9247746
TI  - Genetics of angiotensin I-converting enzyme.
AB  - The ACE gene is constitutively expressed in several types of somatic cells,
      including vascular cells. A soluble form of the enzyme is secreted in plasma by
      proteolytic cleavage of the membrane anchor. The interindividual variability in
      plasma ACE levels is very large, and a family study has indicated that it was
      under the influence of a major gene polymorphism. An insertion (I) deletion (D)
      polymorphism in intron 16 of the ACE gene was then found to be associated with
      plasma and cellular ACE levels. The D allele, which is associated with higher
      plasma ACE levels, and the level of ACE in plasma, were found in case control
      studies to be associated with an increased risk of myocardial infarction, an
      increased risk of diabetic nephropathy in type I diabetic patients, and a faster
      rate of renal function degradation in glomerular diseases. Although these
      findings should be confirmed in prospective studies, they can support the concept
      that ACE level is a critical factor in the determinism of angiotensins and kinins
      (and perhaps also other peptide substrates) levels in peripheral circulations and
      in tissue interstitium, especially in the heart and kidney.

PMID- 9247747
TI  - Renal tissue angiotensins during converting enzyme inhibition in the
      spontaneously hypertensive rat.
AB  - To compare the effects of an angiotensin-converting enzyme inhibitor on
      circulating and tissue renin-angiotensin system (RAS), we measured different RAS
      parameters during the first day of treatment (Day1) as well as after two weeks of
      treatment (Day14). Ramipril was given orally once daily to adult male
      spontaneously hypertensive rats (SHR). Renin activity (RA), angiotensin
      converting enzyme (ACE) activity and levels of angiotensin I (ang I) and
      angiotensin II (ang II) in the plasma, renal cortex and renal medulla were
      assessed at Day1 and Day14 of the treatment. In the plasma, both RA and ang I
      increased 10 to 15 fold one to four hours after acute as well as at Day14 of
      ramipril treatment and then returned to basal values within 24 hours. Plasma ang
      II levels were not significantly decreased at Day1 or Day14. The decrease in the
      ang II/ang I ratio suggested a sustained inhibition of plasma ACE at Day14. In
      the renal cortex and medulla, a clearly different pattern was observed: in
      ramipril treated rats, RA in the renal cortex and medulla did not change at Day1
      but at Day14 we observed a slight and sustained increase in RA. Despite very high
      basal levels of RA, ang I levels in the renal cortex were comparable to those in
      the plasma. The ang I level increased only one-fold one hour after ramipril
      intake at Day1 and Day14. This suggests that angiotensinogen may have a limiting
      role in the synthesis of ang I in the kidney. Ang II levels were slightly higher
      in the renal cortex and medulla than in the plasma suggesting local synthesis of
      the peptide. In the kidney, ang II levels decreased one and four hours after the
      acute or prolonged ramipril treatment and the ang II/ang I ratio was reduced at
      the same time. Our results show that the responses of the plasma and kidney
      components of the RAS to ACE inhibition are different in the plasma and the
      kidney suggesting that the circulating and tissue RAS are at least in part
      independent.

PMID- 9247748
TI  - Differential regulation of angiotensin peptides in plasma and kidney: effects of
      adrenalectomy and estrogen treatment.
AB  - Eight angiotensin peptides [angiotensin-(1-7), angiotensin II, angiotensin-(1-9),
      angiotensin I, angiotensin-(2-7), angiotensin-(2-8), angiotensin-(2-9), and
      angiotensin-(2-10)] were measured in plasma and kidney of adrenalectomized rats
      and estrogen-treated rats. In comparison with sham-operated rats, adrenalectomy
      increased plasma renin levels by 50-fold and reduced plasma angiotensinogen
      levels by 67%. Adrenalectomy increased plasma angiotensin peptide levels by 9- to
      30-fold, but the increases in renal angiotensin peptide levels were much less
      than those seen for plasma. In comparison with vehicle-treated rats, estrogen
      treatment increased plasma angiotensinogen levels by 3-fold and reduced plasma
      renin levels by 41%. Estrogen treatment decreased plasma angiotensin peptide
      levels, whereas renal angiotensin peptide levels increased by as much as 2- to 3
      fold. These results confirm the differential regulation of angiotensin peptide
      levels in plasma and kidney, and provide further support for the essential role
      of angiotensinogen in modulating plasma and tissue angiotensin peptide levels.

PMID- 9247749
TI  - Renin secretion in Lyon hypertensive rats.
AB  - In genetically hypertensive rats of Lyon strain (LH), both development and
      maintenance of hypertension are extremely sensitive to the chronic blockade of
      the renin-angiotensin system. However, LH rats exhibit a low renin secretory
      profile as indicated by (1) low basal plasma renin concentration; (2) blunted
      renin responses to reductions of renal perfusion pressure and beta-adrenoceptor
      stimulation both in vitro (isolated perfused kidney) and in vivo (conscious rat).
      None of the latter abnormalities are corrected by chronic sodium deprivation or
      when hypertension is prevented by hydralazine or perindopril treatment. Future
      studies will therefore have to elucidate the 'renin paradox' in LH rats.

PMID- 9247750
TI  - The renin-angiotensin-aldosterone system in pre-eclampsia.
AB  - Pre-eclampsia is characterised physiologically by plasma volume contraction,
      intravascular coagulation and intense vasoconstriction. It was originally thought
      that the renin-angiotensin-aldosterone (RAA) system would be overactive but
      studies have shown a more complex picture. Plasma renin activity (PRA) and
      concentration (PRC) and plasma angiotensin II (AII) and aldosterone
      concentrations (PAC) are reduced compared to normal pregnancy. Total renin
      concentration is normal and plasma concentrations of high molecular weight
      angiotensinogen are increased in pre-eclampsia though total angiotensinogen is
      normal. PRA and PRC respond appropriately to physiologic stimuli in pre-eclampsia
      except for impaired renin release following frusemide, possibly due to
      prostacyclin deficiency. Although plasma AII concentrations are reduced there is
      heightened pressor sensitivity to infused AII--the mechanism(s) for this are
      unknown. PAC is reduced but the ratio PAC-PRC is twofold greater in pre-eclampsia
      than normal pregnancy. This does not appear to be due to changes in potassium,
      atrial natriuretic peptide, dopamine or ACTH, and may be another manifestation of
      increased (adrenal) sensitivity to AII in pre-eclampsia. There is an inverse
      relationship between the plasma active renin to prorenin ratio and the clinical
      severity of the pre-eclampsia. Understanding the mechanisms producing these
      changes in the RAA system in pre-eclampsia will give strong clues to the overall
      pathogenesis of this disorder.

PMID- 9247751
TI  - Modulation of vascular function by diet and exercise.
AB  - Clinical research is conducted in free living individuals who are always subject
      to the influences on vascular function and the major cardiovascular regulators of
      their lifestyle. The purpose of this paper is to review some lifestyle influences
      on cardiovascular function, particularly the sympathetic nervous system and
      endothelially mediated vasodilatation. There are highly differentiated
      sympathetic responses to feeding, and to acute exercise. Over a longer period
      obesity has a typical pattern of sympathetic activity. Reduced dietary salt
      intake elicits profound localised increases in sympathetic activity to the
      kidney. Marine oil supplementation attenuates the sympathetic responses to
      psychological stress and improves endothelially mediated vasodilatation in
      hypercholesterolaemics. Exercise training reduced total noradrenaline spillover,
      the major beds affected being the renal and skeletal muscle. These examples
      illustrate the dynamic nature of vascular dilatation and that, like the
      sympathetic nervous system, it is modulated by short, medium and long term
      influences. In both cases there is regulation both at a local and systemic level.
      Habitual, and recent, lifestyle can exert important cardiovascular effects which
      must be taken into account in clinical and epidemiological research.

PMID- 9247752
TI  - Stress, coping, lifestyle and hypertension: a paradigm for research, prevention
      and non-pharmacological management of hypertension.
AB  - Lifestyle related factors such as obesity, drinking habits, sodium and potassium
      intake and physical inactivity are well established determinants of high blood
      pressure. The role of psycho-social stressors, and in particular environmental
      work or home stress is far less clear. Some but not all studies using the Karasek
      'job-strain' model have found a relationship with ambulatory blood pressure
      levels. Other studies using more 'subjective' measures of occupational stress
      have found no relationship or even inverse associations with blood pressure. The
      possibility that relationships between external stressors, personality factors
      and blood pressure levels might be mediated or confounded by coping mechanisms
      influencing lifestyle factors known to directly affect blood pressure has not
      been adequately studied. This paper briefly explores the paradigm relating
      environmental psychosocial stress, individual coping mechanisms, lifestyle
      behaviours and blood pressure levels. The issues are critical for research
      methodology in this area and for the development of better behavioural strategies
      for the prevention and nonpharmacological management of hypertension.

PMID- 9247753
TI  - Microalbuminuria in essential hypertension.
AB  - The prevalence of microalbuminuria in patients with essential hypertension ranges
      between 10 and 25%. The level of albuminuria is highly correlated with arterial
      pressure and more closely ambulatory arterial pressure. The interaction between
      albuminuria and arterial pressure is enhanced by overweight and smoking. The
      renal mechanisms of microalbuminuria are not well elucidated; however, an
      increase in filtration fraction suggestive of intraglomerular hypertension was
      observed in patients with hyperfiltration. The significance of microalbuminuria
      as a marker of cardiovascular risk or hypertensive renal damage needs to be
      confirmed through long-term follow-up studies. Antihypertensive treatment has
      variable influence on albuminuria; and angiotensin-converting enzyme inhibitors
      and to a lesser extent other agents, tend to partially correct this abnormality.

PMID- 9247754
TI  - Antihypertensive therapy and diabetic microvascular disease.
AB  - Hypertension is commonly associated with diabetes and may represent either a
      manifestation or a cause of diabetic vascular injury. The following series of
      studies have explored the role of hypertension in accelerating diabetic
      microvascular injury. In addition, the role of various classes of
      antihypertensive agents in preventing or reversing diabetic vascular
      abnormalities in the presence and absence of systemic hypertension was assessed
      in both the experimental and clinical context. The induction of streptozotocin
      diabetes in SHR leads to accelerated development of nephropathy as assessed by
      both functional and structural parameters. ACE inhibitors but not dihydropyridine
      calcium channel blockers favourably influence the progression of experimental
      diabetic nephropathy even in the setting of a normal blood pressure. More recent
      studies have shown that the trophic changes in the mesenteric arteries from
      diabetic rats are also attenuated by ACE inhibition. Preliminary results from the
      Melbourne Diabetic Nephropathy Study Group suggest that the ACE inhibitor,
      perindopril, is more effective than the dihydropyridine calcium channel blocker,
      nifedipine, in retarding the rise in urinary albumin excretion in normotensive
      insulin and noninsulin dependent diabetic patients with microalbuminuria. In
      conclusion, ACE inhibitors appear to be the drugs of choice in prevention and
      treatment of diabetic renal disease and may also act as protective agents at
      other sites of vascular injury.

PMID- 9247755
TI  - Second Australian National Blood Pressure Study (ANBP2). Australian Comparative
      Outcome Trial of ACE inhibitor- and diuretic-based treatment of hypertension in
      the elderly. Management Committee on behalf of the High Blood Pressure Research
      Council of Australia.
AB  - The Second Australian National Blood Pressure Study (ANBP2) is a comparative
      outcome trial being conducted in general practices throughout Australia of ACE
      inhibitor- and diuretic-based treatment in 6000 hypertensive patients aged 65-84
      years. The study is using a prospective randomised open-label design with
      blinding of endpoint assessments. The primary objective is to determine whether
      there is any difference in total cardiovascular events (fatal and non-fatal) over
      a five year treatment period between the two treatment regimens. Eligible
      hypertensive patients (average sitting blood pressure at the 2nd and 3rd
      screening visits > 160 mm Hg systolic and/or > 90 mm Hg diastolic) may be either
      untreated or previously treated and should have no history of recent
      cardiovascular morbidity or serious intercurrent illness. Patients are randomised
      to one of the treatment arms with randomisation stratified for practice and for
      age. Following randomisation each patient's blood pressure is managed by his/her
      general practitioner according to guidelines relevant to each treatment arm. Over
      700 patients have now been randomised with recruitment intended to be complete by
      the end of 1997.

PMID- 9247756
TI  - Influence of gender on the level of pulse pressure: the role of large conduit
      arteries.
AB  - The blood pressure curve may be divided into two components: a steady component
      represented by the mean arterial pressure, and a pulsatile component represented
      by the purse pressure. Whether the contribution of either these two components
      may be different in men and women was not yet investigated. The present study
      used 24 hours ambulatory brachial blood pressure monitoring and determination of
      casual carotid and radial pulse pressure by applanation tonometry to investigate
      320 subjects (199 men and 121 women) with normal or elevated blood pressure. With
      ambulatory blood pressure monitoring, there was no gender influence on the mean
      values of mean and diastolic blood pressure, but men were characterized by a
      significantly higher systolic and pulse pressure (P < 0.001). In women, pulse
      pressure was strongly and positively correlated with systolic (and not diastolic)
      blood pressure. In men, pulse pressure was positively correlated with systolic
      blood pressure and negatively with diastolic blood pressure (P < 0.001). In the
      overall population (men plus women), brachial ambulatory pulse pressure was
      positively correlated with body height and mean arterial pressure (P < 0.001) but
      the latter correlation was stronger in women. Applanation tonometry indicated
      that, whereas carotid pulse pressure was identical in men and women, men had a
      significantly higher radial systolic blood pressure, indicating a gender
      difference in pressure wave transmission. The study provides evidence that men
      and women did not differ in terms of mean arterial pressure, but rather in terms
      of pulse pressure and pressure wave transmission, indicating that large (and not
      only small) arteries modulate the gender difference in the level of blood
      pressure. This finding may have important implications for the diagnosis and the
      clinical management of subjects with hypertension.

PMID- 9247757
TI  - Evaluation of the determinants of flow-mediated radial artery vasodilatation in
      humans.
AB  - The relative importance of the early peak response during hyperaemia and of the
      duration of the hyperaemic phase (t1/2: blood flow velocity half time and
      AUCt1/2: area under the curve of flow velocity at t1/2) in the magnitude of the
      flow-dependent vasodilatation of the radial artery was determined in humans.
      Radial artery diameter was measured continuously in 18 healthy volunteers using
      an echo-tracking system coupled to a Doppler device for the measurement of the
      radial blood flow. In 9 subjects, arterial parameters were measured at baseline
      and during 3 hyperaemic tests performed after 2, 5 or 10 minutes of ischaemia.
      Reproducibility of the measured parameters was studied in 9 other subjects.
      Radial artery diameter, AUCt1/2 and t1/2 increased proportionally with the
      duration of ischaemia. In contrast, the peak flow response was already maximal
      after 5 minutes of ischaemia. The regression analysis showed that the best fit
      model after stepwise analysis only included t1/2 (r = 0.85, p < 0.001). There was
      no correlation between the peak flow values and the duration of hyperaemia (r =
      0.29, p = 0.14). These results demonstrate that conduit arteries postischaemic
      flow-dependent vasodilatation in humans is both determined by the peak value and
      by the duration of the hyperaemic phase and suggest that these two components
      must be considered when comparing this index of NO release between different
      groups of subjects.

PMID- 9247758
TI  - The relationship of blood pressure to cardiac hypertrophy: experimental studies
      in rats.
AB  - Cardiac hypertrophy is an independent predictor of morbidity and mortality. The
      exact relationship between blood pressure, hormones and cardiac hypertrophy is
      unclear. This study was undertaken to determine if intermittent elevation of
      blood pressure could cause left ventricular hypertrophy. Blood pressure was
      elevated intermittently by intraperitoneal injections of angiotensin II,
      noradrenalin and methoxamine. Blood pressure was acutely elevated by 60 mmHg or
      more for periods lasting up to 1 hour on up to 4 occasions each day. Cardiac
      index was measured 2 and 4 weeks after the experiment started. The cardiac index
      was increased by all procedures. The results were complicated by a retardation of
      growth in some experimental groups, meaning that the cardiac weight did not
      increase though the index did. In a study looking at the interaction of sodium
      and angiotensin II high sodium intake caused left ventricular hypertrophy and
      injections of angiotensin II caused further left ventricular hypertrophy. This
      study indicated that acute intermittent elevation of blood pressure could cause
      left ventricular hypertrophy and suggests that wall stress rather than 24 hour
      workload is the important triggering mechanism.

PMID- 9247759
TI  - Blood pressure lowering for the prevention of cognitive decline in patients with
      cerebrovascular disease. PROGRESS Management Committee. Perindopril Protection
      Against Recurrent Stroke Study.
AB  - Cerebrovascular disease and high blood pressure both appear to increase the risk
      of vascular dementia. PROGRESS aims to investigate whether blood pressure
      lowering with an angiotensin coverting enzyme inhibitor-based regimen will reduce
      the risk of cognitive impairment in patients with a history of stroke or
      transient ischaemic attack. A total of at least 6000 patients will be randomised
      to receive perindopril (+/- indapamide) or matching placebo(s), with treatment
      and follow-up scheduled to continue for at least 4 years. Substudies will
      investigate the effects of treatment on cognitive decline in subgroups defined by
      apo-E genotype and on white matter lesions assessed by magnetic resonance
      imaging. Final results from the study should be available in 2001.

PMID- 9247760
TI  - Primary aldosteronism: a new understanding.
AB  - Primary aldosteronism (PAL) may always have a genetic basis. This leads to either
      abnormally regulated, increased biosynthesis (Familial Hyperaldosteronism Type I,
      FHI) or to unrestrained hyperplasia and neoplasia, usually benign. The
      distinction between diffuse hyperplasia, nodular hyperplasia and adenoma may be
      relatively unimportant in functional and etiological terms. The genetic basis
      must be understood before diagnosis of disease (FHI) or of predisposition (all
      other PAL) can be made at birth and appropriate surveillance commenced. The
      natural history of PAL other than FHI is for progressive increase in severity,
      with both adrenals eventually involved. Long-term follow-up of PAL is therefore
      mandatory, and postoperative assessment of residual non-suppressible aldosterone
      production by fludrocortisone suppression testing useful in defining biochemical
      cure or improvement, and the need for specific medical treatment.

PMID- 9247761
TI  - Glucocorticoids and hypertension in man.
AB  - Abnormalities of cortisol production or metabolism are involved in the genesis of
      hypertension in Cushing's syndrome, apparent mineralocorticoid excess and
      liquorice abuse and possibly in chronic renal failure and essential hypertension.
      We have studied the physiological mechanisms by which cortisol raises blood
      pressure in short term studies of cortisol administration in normal men. Cortisol
      induced hypertension cannot be explained by increases in vasopressor or decreases
      in vasodepressor hormone concentrations, or by any increase in sympathetic
      nervous activity. The hypertension is accompanied by substantial sodium retention
      but a significant component of the blood pressure rise is sodium independent. The
      hypertension is characterized by an increase in cardiac output but a rise in
      output is not essential for the rise in blood pressure. Our working hypothesis is
      that cortisol induced hypertension is a consequence of increases in renal
      vascular resistance.

PMID- 9247762
TI  - Aldosterone, salt and cardiac fibrosis.
AB  - The classical effects of aldosterone are mediated via epithelial
      mineralocorticoid receptors (MR), protected against cortisol/corticosterone
      occupancy and activation by the enzyme 11 beta hydroxysteroid dehydrogenase. The
      pathophysiological effects of aldosterone on non-epithelial tissues, in contrast,
      are mediated via unprotected MR in which occupancy by cortisol/corticosterone
      antagonises the effect of aldosterone. Aldosterone raises blood pressure by
      occupying MR in the circumventricular region of the brain, an effect antagonised
      by concomitant intracerebroventricular (ICV) infusion of similar doses of
      corticosterone. Peripheral infusion of aldosterone to salt loaded rats causes
      hypertension, cardiac hypertrophy and cardiac fibrosis; concomitant ICV infusion
      of the MR antagonist RU28318 abolishes the aldosterone-induced hypertension, but
      does not affect cardiac hypertrophy or fibrosis. These peripheral effects of
      aldosterone are presumably via cardiac MR; high glucose/PKC modulated,
      aldosterone-specific effects on protein synthesis have recently been demonstrated
      as direct MR-mediated actions on cultured neonatal rat cardiomyocytes. The
      pathophysiologic effects of aldosterone via nonepithelial MR have a time course
      of days/weeks rather than hours, reflect occupancy of only a small percentage of
      such receptors, and require salt loading. How the effects of salt loading are
      transduced in such circumstances remains to be explored.

PMID- 9247763
TI  - Anger expression and cardiovascular reactivity to mental stress: a spectral
      analysis approach.
AB  - The cardiovascular reactivation to a recently described videogame task i.e. a
      maze test was evaluated in the time and frequency-domain using finger blood
      pressure (BP) measurement in 25 subjects on no medication, including 6 subjects
      with mild hypertension. Prior to BP measures subjects completed the items of the
      State-Trait Anger Expression Inventory questionnaire corresponding to the trait
      anger and anger expression scales. The BP recording session was divided into
      resting, test and recovery periods. A detrending procedure was applied to each
      recording prior to the fast Fourier transform. Systolic BP (SBP) and heart rate
      (HR) were increased during the test. The mid-frequency (MF, 0.1 Hz) components of
      SBP and HR variability were also elevated during the stressful period. In resting
      conditions SBP levels of subjects with low trait anger was lower than in subjects
      with high trait anger (128 +/- 4 mmHg, n = 14 versus 148 +/- 4 mmHg, n = 11, P <
      0.01, Student t test). Nevertheless the average SBP increase due to the stress
      was of similar magnitude in these two subgroups (14 mmHg). A significant negative
      relationship was observed between anger-out expression score and the MF SBP
      variation (r = 0.46, P < 0.05). A significant negative relation was found between
      anger-in mode of expression and the HR peak during the test (r = 0.43, P < 0.05).
      In conclusion, our data suggest that individuals who are often in anger-provoking
      situations (high trait anger) should have heightened BP. Two different patterns
      of cardiovascular responses (SBP variability and HR levels) were observed for the
      outward and inward mode of expression of anger. This may reflect a different
      psychological control of HR levels and BP variability.

PMID- 9247764
TI  - Effect of central endogenous angiotensin II on sympathetic activation induced by
      hypoxia.
AB  - This study examined the possible contribution of the brain renin-angiotensin
      system on the sympathetic activation induced by hypoxia in conscious rabbits.
      Blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA)
      were recorded under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before
      and after fourth ventricular administration of either losartan (10 micrograms in
      25 microliters), enalaprilat (500 ng in 25 microliters) or Ringer's (25
      microliters). Hypoxia increased the RSNA by 113% and slightly decreased HR
      without changing BP. It also increased the variability of BP or HR in the 0.2-0.4
      Hz frequency domain. Losartan and enalaprilat did not change the resting BP or HR
      but elevated the RSNA increase seen during hypoxia. Our results suggest that
      central angiotensin is involved in mediating response to chemoreceptor
      activation.

PMID- 9247765
TI  - Antihypertensive drugs in the stroke-prone spontaneously hypertensive rat.
AB  - The stroke-prone spontaneously hypertensive rat (SHR-SP) is an experimental model
      that has been widely used to investigate the potential preventive effects vs
      stroke and mortality of numerous antihypertensive agents. Among the latter,
      angiotensin I-converting enzyme inhibitors, angiotensin II AT1-receptor blockers
      and calcium antagonists have proven to be very effective. The mechanisms involved
      in their beneficial effects include limitation of the age-related alterations of
      large cerebral arteries' functional parameters, prevention of fibrinoid necrosis
      formation in cerebral arterioles and, to a lesser extent, limitation of the blood
      pressure rise.

PMID- 9247766
TI  - Pharmacological demonstration of the additive effects of angiotensin-converting
      enzyme inhibition and angiotensin II antagonism in sodium depleted healthy
      subjects.
AB  - A blockade of the hemodynamic and tissue effects of angiotensin II (Ang II) more
      complete than that presently achieved with usual daily doses of angiotensin
      coverting enzyme (ACE) inhibitors or type 1 Ang II receptor antagonists has
      potential advantages and risks. Therefore, it is worthwhile to investigate the
      biological and the hemodynamic effects of the simultaneous blockade of the renin
      angiotensin system (RAS) at the two sites where it can be currently achieved, ACE
      and type 1 Ang II receptors. To investigate this issue, 2 double-blind randomized
      crossover studies were performed in a model of mild sodium depletion in
      normotensive volunteers. They ingested single oral doses of captopril 50 mg,
      losartan 50 mg, their combination or matched placebos, and in a second study,
      single oral doses of enalapril 10 mg, enalapril 20 mg and the combination of
      losartan 50 mg with enalapril 10 mg. The combination of captopril 50 mg and
      losartan 50 mg had additive effects on blood pressure fall and renin release in
      sodium-depleted normotensive subjects. When compared to enalapril 10 mg and the
      doubling of its dose, the combination of losartan 50 mg and enalapril 10 mg
      significantly increased both the area under the time curve of mean blood pressure
      fall and plasma active renin levels. It did not further decrease plasma
      aldosterone levels. The conclusion is that a more complete blockade of the RAS
      can be achieved by concomitant administration of a type 1 Ang II receptor
      antagonist and an ACE inhibitor.

PMID- 9247767
TI  - Cardioprotective effect of enalapril in renovascular and angiotensin II
      hypertension.
AB  - The influence of chronic treatment with enalapril or losartan (10 or 30
      mg/kg/24h, respectively) on cardiac mass was evaluated in one-kidney, one clip
      (1K-1C) hypertensive rats submitted to sodium restriction 3 weeks after clipping
      and in rats infused for 10 days with angiotensin II (ANGII: 200 ng/kg/min). In 1K
      1C hypertension, cardiac mass and arterial pressure were reduced to a similar
      extent by enalapril and losartan. In ANGII hypertension, enalapril and losartan
      blunted the increase in cardiac mass whereas losartan but not enalapril prevented
      the development of hypertension. The cardioprotective effect of enalapril was
      attenuated by concomitant blockade of bradykinin receptors (Hoe140: 300
      micrograms/kg/24h) in both models. The beneficial influence of enalapril on
      cardiac mass appears to be independent of its effect on blood pressure and ANGII
      generation and seems partly mediated by endogenous bradykinin in these high ANGII
      models of hypertension.

PMID- 9247768
TI  - Angiotensin II antagonism and pre-glomerular arterial wall dimensions in the
      kidney of the spontaneously hypertensive rat.
AB  - The effects of the angiotensin II type 1 receptor antagonist TCV-116 on the wall
      dimensions of the interlobular and arcuate arteries have been studied. SHR rats
      were treated with TCV-116 between 4 and 10 weeks, at which time their kidneys
      were perfusion-fixed and examined using stereological techniques. TCV-116 reduced
      arterial pressure and left ventricle/body weight ratio, but did not reduce renal
      arterial wall dimensions. For both arcuate and interlobular arteries, wall
      density/kidney ratio was significantly greater in the TCV-116 treated SHR than in
      untreated SHR and wall:lumen ratio was also significantly greater for the
      interlobular arteries in the TCV-116 treated rats. These findings are similar to
      those obtained previously using enalapril, and indicate that hypertrophy of the
      walls of these intra-renal arteries is not secondary to the elevated arterial
      pressure, unlike in other vascular beds.

PMID- 9247769
TI  - Chronic vasopressin antagonism in two-kidney, one-clip renovascular hypertension.
AB  - The role of vasopressin (AVP) in the maintenance of hypertension in the rat model
      of two-kidney, one-clip (2K1C) Goldblatt hypertension was assessed using the
      nonpeptide orally effective V1a receptor antagonist, OPC-21268. Rats were studied
      eight weeks after surgery when mean arterial pressure (MAP) was significantly
      increased in 2K1C rats compared to SHAM operated controls (2K1C 139 +/- 6, SHAM
      106 +/- 3, P < 0.01). Neither acute (OPC-21268, 30 mg/kg) nor chronic (OPC-21268,
      30 mg/kg twice daily) V1a receptor blockade reduced blood pressure in either 2K1C
      or SHAM rats. The results of binding kinetic studies confirmed that OPC-21268 was
      effective at its putative site of action, the V1a receptor in both 2K1C and SHAM
      rats. These results indicate AVP is not involved in the maintenance of blood
      pressure in the 2K1C model of renovascular hypertension.

PMID- 9247770
TI  - Angiotensinogen antisense oligonucleotides and fluid intake.
AB  - The effectiveness of antisense oligonucleotides (ODNs) to angiotensinogen on
      intracerebrovenricularly injected renin induced thirst was investigated. As a
      corollary, information would be gained about the role of centrally synthesised
      angiotensinogen in the neural mechanisms subserving water drinking in rats.
      Stable, easily synthesised phosphorothioate antisense oligonucleotides (18 mer),
      one of which included the sequence encompassing the translation start site, were
      injected into the lateral ventricle of rats. The drinking response to a number of
      dipsogenic stimuli was tested. Antisense significantly reduced (by about 50%) the
      volume of water drunk in response to intracerebroventricular (icv) renin or
      isoproterenol but did not reduce drinking in response to the physiological
      challenge of icv angiotensin II, icv carbachol, intravenous hypertonic saline,
      water deprivation or subcutaneous injection of polyethylene glycol. Only one out
      of four antisense probes gave positive results, while mismatch or scrambled
      oligonucleotides did not inhibit water intake. This finding reduces the
      probability that the results observed are non-specific. In these experiments, an
      ODN specific for angiotensinogen was discovered and was produced easily in large
      enough amounts and stabilised against intracellular nucleases without floss of
      cellular access or biological effect.

PMID- 9247771
TI  - Management of iron deficiency in renal anemia: guidelines for the optimal
      therapeutic approach in erythropoietin-treated patients.
AB  - Much progress has been made in recent years in the management of anemia
      associated with chronic and renal failure with recombinant human erythropoietin
      (r-Hu EPO). However, there remains much debate surrounding the diagnosis and
      treatment of iron deficiency. To ensure that full benefit from erythropoietin
      therapy is received, most patients require iron supplement during treatment.
      There are, however, few guidelines for the use of iron therapy. Iron deficiency
      results in an inadequate response to r-Hu EPO and is the main cause of resistance
      to this treatment. Oral iron therapy is of limited value in patients receiving r
      Hu EPO. Thus, intravenous iron supplementation should be administered only in
      patients who do not tolerate available intravenous iron preparations or who are
      on continuous ambulatory peritoneal dialysis with no evidence of functional iron
      deficiency. This article provides guidelines for the diagnosis of absolute or
      functional iron deficiency in patients with renal anemia and suggests treatment
      schedules for intravenous iron supplementation. We hope that all dialysis
      patients will be able on this basis to achieve a satisfactory iron status and
      benefit fully from r-Hu EPO therapy.

PMID- 9247772
TI  - Serum hyaluronan levels follow disease activity in vasculitis.
AB  - Hyaluronan (HA) is a high molecular weight polysaccharide present in the
      extracellular matrix of most tissues. It is a major component of loose connective
      tissues such as skin, synovial fluid and the vitreous body, and during embryonic
      development, tissue repair, tumor growth and at inflammatory sites. Increased
      serum concentrations have been reported in association with tissue damage,
      certain inflammatory diseases, notably rheumatoid arthritis and scleroderma,
      liver malfunction and in some malignancies. Currently there are no serological
      markers available that monitor the extent of tissue damage in vasculitis. We
      therefore, conducted this study to investigate the significance of serum HA in
      patient with systemic vasculitis (SV). Ten patients with SV and acute renal
      failure had elevated HA levels compared to normal age and gender matched controls
      (n = 31) (mean +/- SD: 673.8 +/- 495.14 micrograms/l and 90.26 +/- 37.18
      micrograms/l, respectively; p < 0.001]. Eight of these patients were studied
      longitudinally for ten days, after pulse steroids, during which serum HA levels
      fell paralleling clinical improvement, despite the persistence of positive
      perinuclear-anti-neutrophil cytoplasmic antibody (p-ANCA) serology in three
      patients. In two patients, the clinical course was complicated by sepsis which
      was accompanied by an acute rise in serum HA. One patient suffered a relapse of
      vasculitis, with lung hemorrhage and a sudden rise in HA (> 2,000 micrograms/l),
      but c-ANCA serology remained normal. Serum HA was also measured in a further ten
      patients in clinical remission from SV and found to be within the normal range
      (82.44 +/- 39.06 micrograms/l). One patient, with equivocal clinical relapse
      after transplantation, exhibited high p-ANCA (404 IU) but serum HA remained
      normal (ten readings over six months 0-163 micrograms/l). Little change was seen
      in symptoms, or HA and ANCA serology, following plasma exchange. These
      preliminary data indicate that serum HA is raised in active vasculitis and may be
      a useful adjunctive marker of disease activity and extent of tissue damage.

PMID- 9247773
TI  - Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay
      Standardization.
AB  - Renal granulomas are a relatively infrequent finding in the kidney biopsy. They
      have been described in a number of syndromes such as Wegener's granulomatosis,
      anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be
      indicative of a fulminant clinical course. In leading textbooks, diverse
      definitions of renal granulomas are presented, which has led to controversies in
      identifying them. This, in combination with their rare occurrence, makes it
      difficult for the general pathologist to identify them. We present the clinical
      data of 16 patients with renal granulomas, from a total group of 157 patients
      with systemic vasculitis. Their renal functioning was not significantly different
      from the other 141 patients in whose renal biopsies renal granulomas were
      present. Furthermore, we present two practical definitions for the recognition of
      renal granulomas in the kidney biopsy, and we show a number of examples of their
      various histopathological shapes.

PMID- 9247774
TI  - High-dose torasemide, given once daily intravenously for one week, in patients
      with advanced chronic renal failure.
AB  - Effects, both acute and after repeated dosing of 200 mg of intravenous torasemide
      in comparison to baseline values on placebo, were investigated with respect to 24
      h fractional volume excretion and electrolyte excretion, signs of peripheral
      edema and changes in body weight in the present open uncontrolled multicenter
      study. Fourty-four patients with advanced chronic renal failure (mean creatinine
      clearance 8.9 +/- 9.6 ml/min, range 1.1-63.7 ml/min) were enrolled after they had
      given their informed consent. The increase vs placebo in the primary efficacy
      variable 24 h fractional volume excretion was statistically significant both
      acutely (p = 0.0001) and after repeated daily injections (p = 0.0012). The acute
      changes of the means of fractional volume excretion (from 14.32% to 21.07%) and
      of absolute 24 h urinary volume (from 1303 ml to 2124 ml) were as expected from
      earlier data. In addition to the acute results our study showed that after seven
      days of daily injections there was still a considerable diuretic effect (mean
      fractional volume excretion: 18.10%, absolute 24 h urinary volume: 1664 ml). Our
      data support earlier results in that the change in fractional potassium excretion
      was considerably smaller than that of sodium of chloride excretion. However, this
      effect which was more pronounced after acute administration of torasemide seems
      to vanish after repeated dosing. After repeated dosing there was only a minor
      change in calcium excretion and there was no alteration in phosphate excretion,
      neither acutely nor with repeated dosing. Along with the enhanced diuresis there
      was a relevant reduction in body weight and a clinical significant improvement
      preexisting signs of peripheral edema. Torasemide was found to be also
      efficacious in patients on hemodialysis (with residual diuresis of > or = 300
      ml): after the first i.v. dose of 200 mg torasemide the mean fractional volume
      excretion was increased from 16.22% at baseline by 3.42% to 18.99% (in absolute
      24 h urinary volume from 1044 ml at baseline by 563 ml to 1607 ml). In parallel,
      the mean fractional sodium excretion was increased from 8.67% at baseline by
      2.99% to 11.14% (in absolute 24 h urinary sodium excretion from 83.3 mmol at
      baseline by 51.2 mmol to 128.0 mmol). There was no serious adverse events related
      to the administration of torasemide. Torasemide appears to be a good choice for
      the treatment of patients with renal failure.

PMID- 9247775
TI  - Importance of volume factors in dialysis related hypertension.
AB  - OBJECTIVE: To evaluate the relation between total body water and dialysis related
      hypertension. PATIENTS AND METHODS: Thirty stable chronic hemodialysis patients
      were studied. Twenty-four-hour ambulatory blood pressure on the day before
      dialysis, blood pressure before and after dialysis, weight gain, ultrafiltration
      and total body water were determined. Total body water was measured by body
      impedance analysis and expressed as percentage of dry weight (TBW %). Ambulatory
      blood pressure recordings were defined as hypertensive when the blood pressure
      load (% of readings above 140/90 mmHg) was more than 40%. RESULTS AND CONCLUSION:
      Patients, classified as normotensive (n = 11) or hypertensive (n = 19), based on
      24-hour blood pressure measurements, had significantly different TBW % (54.7 +/-
      5.3 vs. 58.9 +/- 4.6%, p = 0.046). Ambulatory blood pressure and postdialysis
      blood pressure, but not predialysis blood pressure, were significantly correlated
      with TBW %. Acute volume changes, as reflected by interdialytic weight gain and
      ultrafiltration did not correlate with TBW %. These changes correlated weakly
      with predialysis blood pressure. Multivariate analysis showed that only TBW % and
      antihypertensive medication had an independent influence on 24-hour blood
      pressure measurements. We conclude that 24-hour blood pressure and blood pressure
      after dialysis are better related to total body water than blood pressure before
      dialysis, which was however weakly related to the acute volume overload, induced
      by interdialytic weight gain. We hypothesize that this could be the result of a
      more important chronic volume overload leading to an increase in systemic
      vascular resistance. On the contrary the acute but less important changes in
      extracellular volume between dialyses cause no hypertension after dialysis and no
      sustained hypertension over 24 hours, but only in some cases a temporary increase
      in the blood pressure just before dialysis. This volume overload can be easily
      determined by measurement of total body water by bioelectrical impedance
      analysis.

PMID- 9247777
TI  - Propylthiouracil-induced rapidly progressive glomerulonephritis associated with
      antineutrophil cytoplasmic autoantibodies.
AB  - We present a case study of a 52-year-old female patient with hyperthyroidism
      which had been diagnosed at the age of 35. However, the malfunction of thyroid
      had been poorly controlled. Thyroid function was returning to normal after the
      administration of propylthiouracil (PTU) 300 mg/day, however purpura appeared in
      both lower extremities. Renal function deteriorated rapidly, and the patient was
      admitted to our hospital. According to the biopsies, leukocytoclastic vasculitis
      in the skin was apparent, and crescent formation was observed in the glomerulus.
      Serological examination revealed positive antineutrophil cytoplasmic
      autoantibodies (ANCA) against proteinase 3 (Pr3) and myeloperoxidase (MPO).
      Antinuclear autoantibody was positive. After cessation of PTU and administration
      of prednisolone, the purpura disappeared and ANCA were becoming negative. Renal
      function recovered gradually. Thyroid function was kept within normal range using
      iodine solution. Thus, it is strongly suggested that PTU-induced rapidly
      progressive glomerulonephritis associated with ANCA.

PMID- 9247776
TI  - An evaluation of the effectiveness of oral iron therapy in hemodialysis patients
      receiving recombinant human erythropoietin.
AB  - Iron balance is critical for adequate erythropoiesis in hemodialysis patients
      treated with recombinant human erythropoietin (EPO). The role of oral iron
      therapy in maintaining or replenishing iron stores has not yet been well defined
      in such patients. We undertook a double-blind, placebo-controlled study to
      evaluate the efficacy of oral iron in 49 hemodialysis patients, divided into two
      groups, based on adequate or deficient iron stores. These groups were treated for
      3 months with 150 mg elemental iron (Polysaccharide complex, Central
      Pharmaceuticals) or placebo, twice daily. Laboratory parameters were followed for
      five months. These parameters included: hematocrit (Hct), ferritin, transferrin
      saturation (Tsat), and zinc protoporphyrin (ZPP). A side-effects questionnaire
      was recorded monthly. Our results indicate that iron replete patients show
      evidence of falling iron stores during the study period; this observation was
      identical in both oral iron and placebo subgroups. Iron deficient patients had a
      significantly greater drop-out rate due to side effects when compared to iron
      replete patients (33% vs. 8%), despite equivalent responses to the side-effect
      questionnaire. We conclude: 1) Oral iron fails to maintain iron stores in iron
      replete patients; 2) Iron deficiency observed in this study may be due to poor
      medication compliance rather than side-effects.

PMID- 9247778
TI  - Differential localization of s and e antigens in hepatitis B virus-associated
      glomerulonephritis.
AB  - We report here a case of membranous glomerulonephritis associated with chronic
      hepatitis B (HB) virus infection and describe differential localization of HB
      antigens in glomeruli. The patient showed mild proteinuria and was positive for
      hepatitis B surface (HBs) antigen, hepatitis B envelope (HBe) antigen, and
      antibody to hepatitis B core (HBc) antigen in the serum. The antibody against
      hepatitis C was negative. A renal biopsy revealed membranous glomerulonephritis
      with mesangial proliferation. The immunohistochemical studies using monoclonal
      antibodies localized the HBe antigen along the capillary wall and the HBs antigen
      in the mesangial area. The immunoelectron microscopic study confirmed the
      localization of HB antigens: HBe antigen was located in the subepithelial and
      intramembranous electron dense deposits and HBs antigen in the mesangial
      deposits. Our present results provide the first report of the differential
      localization of HB antigens in glomeruli at both the light and electron
      microscopic levels. The differential localization of HB antigens will provide
      insight into the pathogenesis of membranous glomerulonephritis.

PMID- 9247779
TI  - Tetracycline derivatives, alternative treatment for nocardiosis in transplanted
      patients.
AB  - Nocardiosis is a rare infection in patients with immunosuppression following
      transplantation. Thus far, treatment with sulfa derivatives, when combined with
      immunosuppressive agents, has been shown to carry an unacceptably high rate of
      toxic effects. Therefore, the possibility of using an alternative antimicrobial
      treatment was investigated. The treatment of disseminated Nocardia infection with
      doxycycline or minocycline in patients after either kidney, bone marrow or liver
      transplantation was investigated retrospectively. Three patients were treated at
      The Hadassah University Hospital in Jerusalem. Antibiotic treatment with
      tetracyclines was administered for one to 14 months at a dose of 100 to 600 mg/d.
      Additional seven patients were reviewed from previous published reports. Nine out
      of the ten treated patients had an uneventful recovery. One non-compliant patient
      died of disseminated nocardiosis. In conclusion, the favorable outcome of the
      patients treated with minocycline for Nocardia infection which developed after
      transplantation, suggests that this antibacterial agentis is both effective and
      safe. These data support the recommendation that tetracycline derivatives may be
      considered as an alternative treatment for Nocardia infections in transplanted
      patients.

PMID- 9247780
TI  - Osmolal gap in alcoholic ketoacidosis.
AB  - Severe metabolic acidosis in the setting of alcoholism raises diagnostic and
      therapeutic problems [Levinsky 1994]. Alcoholic ketoacidosis and toxic alcohol
      ingestion can be difficult to distinguish on initial presentation [Litovitz
      1986]. A high osmolal gap associated with increased anion gap acidosis is said to
      be indicative of toxic alcohol poisoning though this is not at all specific
      [Salem and Mujais 1992]. Invasive therapeutic manoeuvers as for toxic alcohol
      poisoning have been recommended empirically before toxicological confirmation
      when very high osmolarity gaps are reached. Herein, we report two cases of high
      anion gap metabolic acidosis with very high osmolal gap due to alcoholic
      ketoacidosis without any evidence of toxic alcohol ingestion.

PMID- 9247781
TI  - Chronic congestive heart failure associated with bilateral renal artery stenosis.
AB  - The sudden onset of pulmonary edema in patients with renal artery stenosis is an
      increasingly recognized entity. Some data also support an association between
      renal artery stenosis and chronic cardiac failure. We report a 60-year-old man
      with chronic renal failure who had most normal arterial blood pressure despite
      highly severe chronic congestive heart failure. Renovascular disease was
      suspected and an arteriography revealed very tight bilateral artery stenosis.
      Removal of stenosis led to both renal and cardiac functions improvement.

PMID- 9247782
TI  - Long-term diuretic therapy in patients with chronic renal failure.
AB  - Ten patients with chronic renal failure from different genesis (serum creatinine
      levels 150-200 mumol/l), were evaluated from the aspect of the effect of the
      diuretic therapy. The effects of furosemide (FUR) and polythiazide (POL) were
      assessed after 3-month application. The mean values of the estimated parameters
      before treatment, after 3-month administration of FUR as a monotherapy and after
      the next 3 months simultaneously used (FUR + POL), presented a stable increase of
      the diuresis, without statistically significant changes of the global renal
      function, and triglyceride disorders. On the contrary, the improvement of
      calciuria through combined using of furosemide and polythiazide is statistically
      and clinically significant.

PMID- 9247783
TI  - Nephrotic syndrome associated with alpha interferon therapy in chronic myeloid
      leukemia.

PMID- 9247784
TI  - Postrenal transplant erythrocytosis, ACE inhibitors and a hypothetical local
      renin-angiotensin system in the bone marrow.

PMID- 9247785
TI  - Hemodialysis and hemoperfusion in the successful treatment of a poisoning with a
      herbicide containing glufosinate ammonium and a surfactant.

PMID- 9247786
TI  - Single or dual lumen long-term hemodialysis catheters--does it matter which?

PMID- 9247787
TI  - Maintenance therapy with intravenous iron in hemodialysis patients receiving
      erythropoietin.

PMID- 9247788
TI  - Severe metabolic alkalosis corrected by hemodialysis.

PMID- 9247789
TI  - Successful pregnancy and long-term follow-up (12 years) in a patient with
      Takayasu arteritis and renovascular hypertension as a first clinical sign.

PMID- 9247790
TI  - Iatrogenic hypercalcemia in hemodialysis patients in spite of the use of low
      dialysate calcium.

PMID- 9247791
TI  - Bibliography of John A. Jane, M.D., Ph.D.

PMID- 9247792
TI  - Managed care and managed golf: lessons for neurosurgery in 1995.

PMID- 9247793
TI  - Anterior midline approaches to the central skull base.
AB  - Anterior midline approaches are safe and appropriate for extradural lesions of
      the central brain base. They are occasionally warranted for intradural lesions as
      well. Transnasal routes expose the clivus well. They are readily expanded
      superiorly, inferiorly, and laterally. Recent innovations are reductive; they
      expand exposure with less facial disassembly. Lateral and most intradural
      extensions of lesions warrant more lateral approaches.

PMID- 9247794
TI  - Innovations in cranial approaches and exposures: anterolateral approaches.

PMID- 9247795
TI  - Transcranial orbital surgery.

PMID- 9247796
TI  - Innovations in surgical approach: lateral cranial base approaches.
AB  - The extradural anterior transpetrosal approach possesses several advantages.
      First, the majority of the dissection is extradural, providing protection to the
      overlying neural structures. Second, only limited retraction of the temporal lobe
      is necessary, protecting venous outflow via the vein of Labbe'. Third,
      transposition of cranial nerves or vascular structures in unnecessary. Fourth, it
      enjoys natural compatibility with other surgical approaches to enhance exposure
      of the posterior cavernous sinus and petroclival region. The disadvantages are
      mostly related to the unfamiliar anatomy. Most surgeons are not accustomed to
      visualizing petrous apical anatomy from the middle fossa orientation. Therefore,
      practice of this technique in the cadaver laboratory is a mandatory prerequisite
      to its performance in the operating room. The cochlea, carotid artery, labyrinth,
      and cranial nerves five through eight are all at risk during drilling and
      dissection. When performed properly, this technique provides a solid adjunct to
      treating complex lesions of the central cranial base.

PMID- 9247797
TI  - Transpetrosal and combination approaches to skull base lesions.

PMID- 9247798
TI  - The transcondylar approach to the lower clivus, foramen magnum and C1-C2.

PMID- 9247799
TI  - Surgical approaches to aneurysms of the upper basilar artery.

PMID- 9247800
TI  - Treatment of craniosynostosis.

PMID- 9247801
TI  - Electrophysiologic monitoring during tethered spinal cord release.

PMID- 9247802
TI  - Clinical evaluation of cutaneous lesions of the back: spinal signatures that do
      not go away.

PMID- 9247803
TI  - The borderlands of the primary tethered cord syndrome.
AB  - The PTCS is easily dealt with surgically with little risk of additional injury.
      The likelihood of some improvement in neurologic function and the elimination of
      pain is high, with the exception of the neurogenic bladder. In the patient with
      the position of the conus over the L3 vertebral body of below, the rationale of
      therapeutic or prophylactic surgery is clear. As for the patient with progressive
      symptoms attributable to the PTCS, and in the young asymptomatic child or infant
      if the conus is above the L2-L3 disc space, the patient should be assessed in the
      context of the other associated anomalies present.

PMID- 9247804
TI  - The adult with a tethered cord.

PMID- 9247805
TI  - Decade of the brain lecture.. Congress of Neurological Surgeons.

PMID- 9247806
TI  - Neurotrophin infusion improves cognitive deficits and decreases cholinergic
      neuronal cell loss after experimental brain injury.

PMID- 9247807
TI  - Lumbar discectomy microdiscectomy: "the gold standard".

PMID- 9247808
TI  - Is there a future for percutaneous intradiscal therapy?

PMID- 9247809
TI  - The case for posterior lumbar interbody fusion.

PMID- 9247810
TI  - Spinal instrumentation for degenerative disease.

PMID- 9247811
TI  - Acquired lumbar spinal stenosis.
AB  - Based on the individual clinical presentation and radiographic findings, an
      operation that completely decompresses the neural elements in the spinal canal
      and neural foramina followed by posterior, posterolateral, or interbody fusion,
      with or without instrumentation should be the procedure of choice in the future.
      The introduction of pharmacological agents to decrease scarring around the
      decompressed nerve roots will also increase the number of successful procedures.
      It must be stressed, however, that any new operative technique must be tested in
      a rigorous fashion, ideally with a prospective randomized clinical trial.

PMID- 9247812
TI  - Innovation through minimalism: assessing emerging technology in neurosurgery.

PMID- 9247813
TI  - Minimalism through stereotactic technique.

PMID- 9247814
TI  - Minimalism through intraoperative functional mapping.
AB  - Intraoperative stimulation mapping may be used to avoid unnecessary risk to
      functional regions subserving language and sensori-motor pathways. Based on the
      data presented here, language localization is variable in the entire population,
      with only certainty existing for the inferior frontal region responsible for
      motor speech. Anatomical landmarks such as the anterior temporal tip for temporal
      lobe language sites and the posterior aspect of the lateral sphenoid wing for the
      frontal lobe language zones are unreliable in avoiding postoperative aphasias.
      Thus, individual mapping to identify essential language sites has the greatest
      likelihood of avoiding permanent deficits in naming, reading, and motor speech.
      In a similar approach, motor and sensory pathways from the cortex and underlying
      white matter may be reliably stimulated and mapped in both awake and asleep
      patients. Although these techniques require an additional operative time and
      equipment nominally priced, the result is often gratifying, as postoperative
      morbidity has been greatly reduced in the process of incorporating these surgical
      strategies. The patients quality of life is improved in terms of seizure control,
      with or without antiepileptic drugs. This avoids having to perform a second
      costly operative procedure, which is routinely done when extraoperative
      stimulation and recording is done via subdural grids. In addition, an aggressive
      tumor resection at the initial operation lengthens the time to tumor recurrence
      and often obviates the need for a subsequent reoperation. Thus, intraoperative
      functional mapping may be best alluded to as a surgical technique that results in
      "minimalism in the long term".

PMID- 9247815
TI  - Innovations in minimalism: intraoperative MRI.

PMID- 9247816
TI  - Intraoperative cranial navigation.

PMID- 9247818
TI  - Thoracoscopic spinal surgery.

PMID- 9247817
TI  - Magnetic neurosurgery: image-guided, remote-controlled movements of neurosurgical
      implants.

PMID- 9247819
TI  - Percutaneous lumbosacral fixation and fusion: anatomical study and two-year
      experience with a new method.

PMID- 9247820
TI  - Clinical neurosurgery interactive audience participation 1995.

PMID- 9247821
TI  - Lay health advisor intervention strategies: a continuum from natural helping to
      paraprofessional helping.

PMID- 9247822
TI  - Recruitment and training issues from selected lay health advisor programs among
      African Americans: a 20-year perspective.
AB  - The use of lay health advisors (LHAs) to address the health disparity among
      African Americans is well documented and considered a culturally appropriate
      model of community health promotion. The recruitment and training of LHAs are
      important components of the model but have not been fully explored in the LHA
      literature. Recruitment and training of LHAs should reflect both the existing
      roles they have in their respective communities and those proposed by the
      programs to which they are recruited. This article reviews and describes the
      components of recruitment and training as implemented in selected LHA programs
      among African Americans. The article will address the role and purpose of LHAs in
      health promotion among African Americans, a historical perspective of recruitment
      and training, recruitment and training methods in selected LHAs programs for
      African Americans, and recommendations for the recruitment and training of LHAs
      for health promotion among African Americans.

PMID- 9247823
TI  - Lay health advisors: a strategy for getting the word out about breast cancer.
AB  - Transforming natural helpers into lay health advisors (LHAs) is a complex
      undertaking. Using the North Carolina Breast Cancer Screening Program (NC-BCSP)
      as a case study, this article describes the steps involved in developing,
      implementing, and evaluating an LHA intervention, considering factors that make
      the LHA approach appropriate for the NC-BCSP's population, setting, and health
      focus. The authors review five phases of implementation (start-up, training, LHA
      activities, follow-up, resource mobilization) and discuss the NC-BCSP's
      evaluation strategies and tools in light of difficulties involved in assessing
      natural helping processes and impact. Program challenges related to resource
      needs, identification of natural helpers, and LHA monitoring and support also are
      considered. The authors describe ways in which one large group of older, rural,
      African American LHAs are helping establish countywide partnerships between
      health care providers, agencies, and local communities that support and sustain
      individual changes in health behavior.

PMID- 9247824
TI  - Changes in empowerment: effects of participation in a lay health promotion
      program.
AB  - The Camp Health Aide Program is a lay health promotion program for migrant and
      seasonal farmworkers. The program increases access to health care while
      facilitating leadership development and empowerment of individual farmworkers
      through training and experience as lay health promoters (camp health aides
      [CHAs]). This article describes a study which documents impacts on the CHAs of
      working as lay health promoters in terms of changes in personal empowerment. The
      authors developed a working definition of personal empowerment and interviewed 27
      CHAs at three program sites (Arizona, New Jersey, and Florida) at three different
      times. CHAs are grouped in five descriptive categories reflecting varying degrees
      of change in empowerment over this period. Of the total group of 27 CHAs, 24
      exhibited some increase in personal empowerment during the study period. These
      changes are described in detail, and implications are discussed.

PMID- 9247825
TI  - "It's a 24-hour thing ... a living-for-each-other concept": identity, networks,
      and community in an urban village health worker project.
AB  - Social networks are webs of relationships between individuals, and they play an
      important role in the complex social processes through which individuals seek
      information, obtain social support, and mobilize for collective action to modify
      social, economic, and environmental conditions associated with health and
      illness. Studies have described and evaluated lay health advisor (LHA) programs
      that use social networks to improve individual and community health. The
      experience and perceptions of community members involved with LHA programs have
      been explored less often and offer essential information to health educators
      about the design, implementation, evaluation, and support of such programs. This
      article examines the perspective of LHAs in Detroit, Michigan. Their
      understanding and experience of their work, the relationships between their
      activities and a sense of self and community, and personal and programmatic
      rewards and challenges are examined. The authors discuss implications for health
      educators related to LHAs' roles, relationship to supporting organizations,
      recruitment, training, and ongoing support.

PMID- 9247826
TI  - Developing capacities of youth as lay health advisors: a case study with high
      school students.
AB  - Youth lay health advising, a form of support or helping, is an important
      potential resource for preventive intervention. This article describes a case
      study of a youth lay health advising program designed to provide high school
      students with support and guidance to handle challenges and concerns related to
      their health and quality of life. First, the planning, program development, and
      implementation of the approach are described. Second, a rapid formative
      evaluation presents quantitative and qualitative information on adolescent issues
      faced, the types and content of interactions, and peer helper satisfaction with
      the program. Third, the strengths and challenges of the peer helping program and
      the role of youth as lay health advisors are discussed. The article concludes
      with a discussion of the implications for practitioners on this approach to
      building the capacity of adolescents as lay advisors for community health.

PMID- 9247827
TI  - The Latino Health Advocacy Program: a collaborative lay health advisor approach.
AB  - There have been numerous calls in the literature for health educators to develop
      programs to improve access to and utilization of health and human services by
      traditionally underserved communities, including Latinos. While the literature
      suggests several principles that can guide the development of these programs, it
      is important to address the needs, and build on the strengths, of the specific
      community of interest. It is, therefore, important to use collaborative
      approaches in which community members take an active role in the initiation,
      design, implementation, and evaluation of program activities. Lay health advisor
      programs are particularly well suited to this approach as they are designed to
      build on the strength of already existing community relationships to improve
      community health. This article describes a collaborative, culturally appropriate,
      holistic, and ecological lay health advisor program--the Latino Health Advocacy
      Program. Lessons learned and implications for future program development are
      discussed.

PMID- 9247828
TI  - Community health workers: who they are and what they do.
AB  - Community health workers (CHWs) are community members who serve as frontline
      health care professionals. They generally work with the underserved and are
      indigenous to the community in which they work-ethnically, linguistically,
      socioeconomically, and experientially. This article presents the results of a
      survey of 197 systematically selected health care providers in eight Bay Area
      counties. The authors found that 25% of the health care providers in these eight
      counties hire CHWs. The hiring projections indicate that opportunities are
      expanding for these frontline professionals; the majority of growth is in public
      health departments and community-based organizations. The majority of CHWs are
      women (66%) of color (77%) with a high school degree or less (58%). A total of
      44% earn an annual salary of $20,00 to $25,000; 30% make more than $25,001. AIDS
      and maternal and child health are the two major content foci of CHW work.

PMID- 9247829
TI  - Surveillance of nosocomial infections: a fundamental ingredient for quality.

PMID- 9247830
TI  - Nosocomial infections in HIV-infected patients: preliminary results from a
      multicenter surveillance system (1989-1995).
AB  - OBJECTIVE: To describe the characteristics of and trends in nosocomial infection
      among human immunodeficiency virus (HIV)-infected patients. DESIGN: Multicenter
      prospective cohort study. SETTING/PATIENTS: HIV-infected patients were enrolled
      at time of first inpatient admission at five Veterans' Administration Medical
      Centers (VAMCs). RESULTS: As of March 1995, 2,541 patients with 6,625 inpatient
      admissions had been monitored in the five VAMCs. A total of 530 nosocomial
      infections were detected using standard Centers for Disease Control and
      Prevention definitions. Overall distribution by infection site was 31% for
      primary bloodstream infections (BSIs), 28% for urinary tract infections, 15% for
      pneumonia, and 26% for all other sites. Of BSIs, 63% were central line-associated
      bloodstream infections (CLABs). The rate of CLABs per 1,000 central line days was
      6.5 (range, 2.3-8.3) for all patients from participating hospitals, similar to
      the median CLAB rate of 6.0 for patients in medical intensive-care units (ICUs)
      of National Nosocomial Infections Surveillance (NNIS) System hospitals from
      January 1990 through September 1994. For ICU-specific CLABs, the rate from
      hospitals reporting at least one ICU CLAB was 12.7 (range, 12.1-13.1), comparable
      to the 90th percentile of NNIS hospital medical ICUs (13.1). Staphylococcus
      aureus, associated with 35% of BSIs, was the most common nosocomial BSI pathogen.
      Our data demonstrated the following: 13 (10%) of 134 patients with CD4 counts >
      or = 200 cells/mm3 had a CLAB, compared with 61 (6%) of 1,011 patients with CD4
      counts < 200 cells/mm3, P = .08; the per-day risk of CLABs did not change with
      increased duration of catheterization (P = .4); and the per-day risk of a
      temporary (ie, short-term) CLAB was greater than that of a permanent CLAB (P <
      .001). CONCLUSIONS: The data suggest that HIV-infected patients were at higher
      risk of acquiring a BSI than were patients in the NNIS population; patients with
      CD4 counts > or = 200 cell/mm3 and temporary central lines were at increased risk
      for BSI, perhaps reflecting widespread prophylaxis with trimethoprim
      sulfamethoxazole among patients with CD4 counts < 200 cells/mm3, and, in contrast
      to most studies, S aureus, not coagulase-negative Staphylococcus, was the most
      common BSI pathogen.

PMID- 9247831
TI  - Automated entry of hospital infection surveillance data.
AB  - OBJECTIVE: To assess the accuracy of an automated data entry system employing
      optical scanning technology and to provide an analysis of its costs as compared
      to manual data entry. DESIGN: The accuracy and cost of automated data entry of
      100 surgical-wound infection surveillance questionnaires was compared to manual
      entry. SETTING: The Surgical Directorate, The Royal Hospitals, Belfast, Northern
      Ireland. RESULTS: The use of optical scanning technology greatly improved the
      speed and accuracy of data entry. The time spent by the keyboard operator on data
      entry was reduced substantially. For each surgical-wound infection questionnaire
      automatically processed, there was a saving in clerical time equivalent to $0.63.
      The automated data entry process resulted in a 22-fold productivity increase
      compared to manual data entry with validation. After validation, an error rate of
      < 0.2 errors per 1,000 responses was detected in automatically entered data
      compared to a rate of 12.4 errors per 1,000 responses for manually entered data.
      The automated system, including validation, provided a seven-fold productivity
      increase compared to "quick-and-dirty" manual data entry without validation.
      CONCLUSION: Hospital information technology systems may achieve total integration
      of data management, but realistically this would appear to be very much in the
      future. Until then, in view of the accuracy and substantial savings in time and
      money, we recommend the use of automated data entry technology. This system would
      be especially useful where data are transported from outlying hospitals to a
      central receiving center for collation and analysis.

PMID- 9247832
TI  - Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant
      Klebsiella pneumoniae in the United States, 1986 to 1993. The National Nosocomial
      Infections Surveillance System.
AB  - BACKGROUND: In addition to single-hospital outbreaks, interhospital transmission
      of extended-spectrum beta-lactam-resistant (ESBLR) Klebsiella pneumoniae has been
      suspected in some reports. However, these studies lacked sufficient
      epidemiological information to confirm such an occurrence. METHODS: We reviewed
      the surveillance data reported to the National Nosocomial Infections Surveillance
      (NNIS) System during 1986 to 1993 for K pneumoniae isolates and their
      susceptibility to either ceftazidime, cefotaxime, ceftriaxone, or aztreonam.
      Pulsed-field gel electrophoresis (PFGE) was used to study available ESBLR K
      pneumoniae isolates. RESULTS: Among 8,319 K pneumoniae isolates associated with
      nosocomial infections, 727 (8.7%) were resistant or had intermediate-level
      resistance to at least one of these antibiotics. One hospital (hospital A)
      accounted for 321 isolates (44.2%) of ESBLR K pneumoniae. During 1986 to 1993,
      the percentage of K pneumoniae isolates that were ESBLR increased from 0 to 57.7%
      in hospital A, from 0 to 35.6% in NNIS hospitals 0 to 20 miles from hospital A
      (area B), and from 1.6 to 7.3% in NNIS hospitals more than 20 miles from hospital
      A, including hospitals located throughout the United States. Analysis of PFGE
      restriction profiles showed a genetic relationship between a cluster of isolates
      from hospital A and some isolates from one hospital in area B, and consecutive
      admission in these two hospitals was confirmed for two patients from whom
      isolates were available. CONCLUSIONS: These data provide evidence of
      interhospital transmission of ESBLR K pneumoniae in one region of the United
      States and stress the interrelationship between hospitals when trying to control
      antimicrobial resistance.

PMID- 9247833
TI  - Association of private isolation rooms with ventilator-associated Acinetobacter
      baumanii pneumonia in a surgical intensive-care unit.
AB  - OBJECTIVE: To determine the rates and routes of Acinetobacter baumanii
      colonization and pneumonia among ventilated patients in a surgical intensive-care
      unit (SICU) before and after architectural modifications. DESIGN: A nonsequential
      study comparing two groups of patients. All isolates from systematic and clinical
      samples were genotyped by pulsed-field gel electrophoresis (PFGE). Records of
      patients hospitalized during the first and second periods were reviewed and
      findings were compared. Between the two periods, the SICU was remodeled from
      enclosed isolation rooms and open rooms to only enclosed isolation rooms with
      handwashing facilities in each room. SETTING AND PATIENTS: All patients
      hospitalized and mechanically ventilated for more than 48 hours in the 15-bed
      SICU of the University Hospital of Besancon (France). RESULTS: For the first and
      second periods, the rates of colonization were, respectively, 28.1% and 5.0% of
      patients (P < 10(-7); relative risk [RR], 2.23; 95% confidence interval [CI95],
      1.8-2.75) and the specific rates of bronchopulmonary (BP) colonization were,
      respectively, 9.1 and 0.5 per 1,000 days of mechanical ventilation (P < 10(-5).
      Seven major PFGE isolate types were identified, 4 of which were isolated from 44
      of the 47 colonized or infected patients. Logistic regression analysis showed
      that colonization was not associated with patient characteristics. CONCLUSION:
      Conversion from open rooms to isolation rooms may help control nosocomial BP
      tract acquisition of A baumanii in mechanically ventilated patients hospitalized
      in an SICU.

PMID- 9247834
TI  - Controlling varicella in the healthcare setting: the cost effectiveness of using
      varicella vaccine in healthcare workers.
AB  - OBJECTIVE: To determine if varicella vaccination of healthcare workers would
      result in a net cost savings. DESIGN: A Markov-based decision analysis. SETTING:
      The analysis was based on a hypothetical population of healthcare workers. Data
      were obtained from exposure records of a tertiary-care hospital and from the
      literature. Workers were considered potentially susceptible if they had no past
      history of varicella. RESULTS: Vaccination of potentially susceptible workers
      would result in a net cost savings of $59 per person. Serological testing prior
      to vaccination resulted in smaller net savings. The results were robust across a
      wide range of assumptions. Importantly, however, the result was very dependent on
      infection control policy regarding work restrictions for vaccine recipients. If
      more than 3% of vaccinees were removed from work due to vaccine-associated rash,
      vaccination no longer would result in a net cost savings. CONCLUSION: Varicella
      vaccination of potentially susceptible healthcare workers can reduce costs and
      decrease morbidity. Infection control policy regarding work restrictions for
      vaccine recipients will play a key role in the feasibility of vaccination.

PMID- 9247835
TI  - An outbreak of Pseudomonas aeruginosa related to contaminated urodynamic
      equipment.
AB  - Investigation of an outbreak of multiresistant Pseudomonas aeruginosa urinary
      tract infections within our hospital identified the urodynamic laboratory as the
      point source. Disinfection procedures were inadequate, and transducers designated
      for single-patient use were used repeatedly and subsequently became contaminated.
      These improper procedures were part of a cost-containment effort.

PMID- 9247836
TI  - A pseudo-outbreak of respiratory infection with Acinetobacter species.
AB  - We describe an apparent outbreak of respiratory infection with Acinetobacter
      species involving 14 patients over 8 days. Epidemiological investigation revealed
      two consecutive pseudo-outbreaks of infection caused by two consecutive,
      unrelated laboratory errors in the processing of sputum, nasopharyngeal, and
      endotracheal aspirates.

PMID- 9247837
TI  - Basics of surveillance--an overview.
AB  - Surveillance of nosocomial infections is the foundation of an infection control
      program. This article describes components of a surveillance system, methods for
      surveillance, methods for case-finding, and data sources. We encourage the
      epidemiology team to use this background information as they design surveillance
      systems that meet the goals of their individual institution's infection control
      program.

PMID- 9247839
TI  - State of the art--treatment of peripheral occlusive arterial disease (POAD) with
      drugs vs. vascular reconstruction or amputation.
AB  - Peripheral occlusive arterial disease (POAD) is a disease with a progressive
      course in about half of the patients affected. The Fontaine stage II and III have
      been treated not always successfully in the last decades with physical exercise,
      vasoactive substances (pentoxifyllin, naftidrofuryl, buflomedil) and with
      alprostadil. Recently methods of vascular surgery such as PTA, stent implantation
      and bypass operations are introduced in the treatment of Fontaine POAD stages III
      and IV, but these procedures are not recommended in patients younger than 50
      years in order to delay amputation of a limb. The vasoactive substances are seen
      in a new light, because they improve processes of the microcirculation such as
      decreasing plasma viscosity, the raised plasma fibrinogen level and increasing
      the deformability of red blood cells and inhibiting platelet aggregation.
      According to a number of studies pentoxifylline and naftidrofuryl may delay the
      progression of arteriosclerosis. Therefore, a new concept of the treatment of
      POAD must be evaluated (1) resulting in a combination of vascular surgery and
      intermittent drug therapy with vasoactive agents, (2) leading to a decrease in
      the risk of amputation frequency and (3) reducing the treatment costs in spite of
      a higher frequency of the disease and a longer average life expectancy.

PMID- 9247840
TI  - Effect of cimetidine on the pharmacokinetics of the metabolites of metamizol.
AB  - Metamizol (dipyrone) is hydrolyzed in the gastrointestinal tract to the
      pharmacologically active metabolite 4-methyl-amino-antipyrine (4-MAA), which is
      transformed by both, oxidation to 4-formyl-amino-antipyrine (4-FAA) and
      demethylation to 4-amino-antipyrine (4-AA). 4-AA is acetylated to 4-acetyl-amino
      antipyrine (4-AcAA). The aim of the present study was to investigate whether
      cimetidine will alter the pharmacokinetics of the metabolites of metamizol due to
      cimetidine-induced inhibition of the metabolic transformation of 4-MAA. The study
      was carried out in 12 patients with duodenal ulcer treated with cimetidine 1,000
      mg daily over 20 days. A single oral dose of metamizol 1,500 mg was administered
      2 days prior to commencement of cimetidine therapy to all patients. Two further
      doses of 750 and 1,500 mg of metamizol were given in a randomized order on days 8
      and 13 during cimetidine treatment. Blood samples for determination of metamizol
      metabolites were drown over 48 hours post dose. Drug assays for metamizol
      metabolites and cimetidine were performed using HPLC methods. The patients were
      phenotyped for CYP2D6 and acetylation polymorphism. The results revealed that
      cimetidine interacted with 4-MAA by increasing the systemic availability,
      prolonging the elimination half-life and decreasing the systemic clearance of 4
      MAA, whereas the renal clearances of 4-MAA remained unchanged. Consistent with
      cimetidine-induced changes in the oxidation of 4-MAA to 4-FAA, as well as in the
      demethylation of 4-MAA to 4-AA, were the decreased rates of production and the
      lower maximum concentrations of 4-FAA and 4-AA when metamizol was administered
      during cimetidine treatment (p < 0.05). No correlation was found between the
      decrease in the production rates of 4-FAA induced by cimetidine and the
      hydroxylation abilities of the patients, this suggesting that CYP2D6 is not
      involved in the metabolism of 4-MAA to 4-FAA. The acetylation of 4-AA to 4-AcAA
      was not affected by cimetidine. Cimetidine produced an increase not proportional
      to the dose in the systemic availability only of 4-MAA, whereas the kinetics of
      the other metabolites changed proportionally to the increasing dose of metamizol.

PMID- 9247841
TI  - Propylthiouracil-induced cutaneous vasculitis.
AB  - Cutaneous reactions to propylthiouracil and methimazole occur in 3%-5% of adults.
      Generalized maculopapular and papular purpuric eruptions are perhaps the most
      common thionamide-induced reactions. We report 3 patients who developed cutaneous
      vasculitis which is a rare and serious side-effect during antithyroid drug
      therapy. The observation of cutaneous vasculitis during administration of
      propylthiouracil suggested that clinical awareness of this complication should be
      of considerable importance.

PMID- 9247842
TI  - Pharmacokinetics and pharmacodynamics of tolterodine in man: a new drug for the
      treatment of urinary bladder overactivity.
AB  - The aim of this study was to determine the pharmacokinetics, pharmacodynamics,
      and safety of tolterodine following single oral and intravenous doses in healthy
      volunteers. A secondary aim was to identify major urinary metabolites and
      determine mass balance. Single oral doses of 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, and
      12.8 mg of tolterodine (as the tartrate salt) were given to 17 healthy male
      volunteers. Two intravenous doses (0.64 and 1.28 mg) were administered to 8 of
      the volunteers and mass balance was studied after a single oral dose of 5 mg
      (14C)-tolterodine in 6 subjects. Tolterodine was rapidly absorbed following oral
      administration (time to peak serum concentration 0.9 +/- 0.4 h). The absolute
      bioavailability was highly variable, ranging from 10 to 70%. The volume of
      distribution at steady-state ranged from 0.9 to 1.6 l/kg and systemic clearance
      ranged from 0.23 to 0.52 l/h/kg, which resulted in a terminal half-life of 2-3 h.
      Tolterodine exhibited high first-pass metabolism and 2 hepatic metabolic pathways
      were identified: oxidation and dealkylation. Independent of route of
      administration, < 1% of the parent compound was excreted unchanged in urine. Five
      metabolites were structurally identified in urine. Following oral administration
      of (14C)-tolterodine, the excretion of radioactivity into urine and feces was 77
      +/- 4.0% and 17 +/- 3.5%, respectively. Tolterodine decreased stimulated
      salivation after 3.2 mg, increased heart rate after 6.4 mg, and nearpoint of
      vision after 12.8 mg. Six of 8 subjects reported micturition difficulties after a
      dose of 12.8 mg. The lack of a direct relationship between tolterodine serum
      concentrations and effects on stimulated salivation suggested the presence of
      pharmacologically active metabolite(s).

PMID- 9247843
TI  - The homoeopathic treatment of otitis media in children--comparisons with
      conventional therapy.
AB  - In a prospective observational study carried out by 1 homoeopathic and 4
      conventional ENT practitioners, the 2 methods of treating acute pediatric otitis
      media were compared. Group A received treatment with homoeopathic single remedies
      (Aconitum napellus, Apis mellifica, Belladonna, Capsicum, Chamomilla, Kalium
      bichromicum, Lachesis, Lycopodium, Mercurius solubilis, Okoubaka, Pulsatilla,
      Silicea), whereas group B received nasal drops, antibiotics, secretolytics and/or
      antipyretics. The main outcome measures were duration of pain, duration of fever,
      and the number of recurrences after 1 year, whereby alpha < 0.05 was taken as
      significance level. The secondary measures were improvement after 3 hours,
      results of audiometry and tympanometry, and necessity for additional therapy.
      These parameters were only considered descriptively. The study involved 103
      children in group A and 28 children in group B, aged between 6 months and 11
      years in both groups. For duration of pain, the median was 2 days in group A and
      3 days in group B. For duration of therapy, the median was 4 days in group A and
      10 days in group B: this is due to the fact that antibiotics are usually
      administered over a period of 8-10 days, whereas homoeopathics can be
      discontinued at an earlier stage once healing has started. Of the children
      treated, 70.7% were free of recurrence within a year in group A and 29.3% were
      found to have a maximum of 3 recurrences. In group B, 56.5% were free of
      recurrence, and 43.5% had a maximum of 6 recurrences. Out of the 103 children in
      group A, 5 subsequently received antibiotics, though homoeopathic treatment was
      carried through to the healing stage in the remaining 98. No permanent sequels
      were observed in either group.

PMID- 9247844
TI  - Is the biopharmaceutical quality of extracts adequate for clinical pharmacology?
AB  - According to definition, an extract is a multi-substance mixture from a medicinal
      plant obtained by extraction of specific parts of the plant. Corresponding to the
      active ingredients in each case, each extract exhibits, qualitatively and
      quantitatively, a specific content spectrum, so that an extract is not just any
      extract. With an increasing demand for demonstrating the clinical efficacy of
      plant-based substances, extracts or extract fractions, we necessarily confront
      the problem of phytogenerics, i.e. extract-identical preparations for exchange
      versus the innovator. Up to now, pharmacognosic experts, phytochemists, and
      pharmacists have dealt with the problem as to the bioequivalence of
      phytopharmaceuticals within the context of pharmaceutical and
      biopharmaceutical/technological equivalence. In the meantime, however, from a
      number of plant extracts, the active ingredients determining their efficacy are
      known and analytical methods have been established, so that
      bioavailability/bioequivalence studies similar to those for chemical/synthetic
      substances are now possible.

PMID- 9247845
TI  - The hemoglobin polymorphism of the Sardinian wild dwarf horse and the oxygen
      binding properties of the four different horse hemoglobins.
AB  - A study was made of the Hb phenotype of the Sardinian dwarfhorse (Equus caballus
      jara), one of the last surviving wild horse species in Europe. Hb haplotypes and
      their frequencies were found to be similar to those described in the Arabian
      horse (BI = 0.551, BII = 0.389, A = 0.036, V = 0.015), which suggests possible
      introduction onto the island from North Africa. The oxygen binding properties of
      the whole hemolysates and of the four different horse Hbs, separated by ion
      exchange chromatography, were considered with regard to the effect of chloride,
      2,3-bisphosphoglycerate and lactate. Results indicate that no differences exist
      in the four components that characterize horse Hb. The molecular basis of the
      intrinsically low oxygen affinity and of the weak interaction of horse Hb with
      2,3-bisphosphoglycerate is discussed in the light of the primary structure of the
      molecule.

PMID- 9247846
TI  - Social and medical factors affecting hospital discharge of persons with HIV/AIDS.
AB  - Although outpatient care and pharmaceuticals have rendered community-based care
      possible, hospitals remain the locus of the most costly and intensive HIV/AIDS
      care. Little is know, however, about the impact of patients' social circumstances
      upon hospital length of stay. This paper examines the impact of housing status,
      living arrangements, and a range of barriers to discharge on hospital length of
      stay. Findings are based on retrospective medical chart reviews by nurses and
      social workers of 749 HIV/AIDS hospitalizations, occurring between June-August
      1991 in four New York City medical centers. One third of the sample experienced
      at least one barrier to discharge. Medical need barriers were the most common
      (18%), and were associated with the longest length of stay (35.3 days), followed
      by home care and housing barriers (32.7 and 30.2 days, respectively). Fourteen
      percent of the sample were either homeless or in unstable housing situations
      (e.g., transient or "doubled up") prior to admission. Homelessness and unstable
      housing were associated with a 5 day increment in hospital length of stay, and
      remained a significant factor even controlling for morbidity. These results
      indicate that inadequate housing remains a significant barrier to discharge among
      hospitalized persons with HIV/ AIDS.

PMID- 9247847
TI  - Regular exercise in 30- to 60-year-old men: combining the stages-of-change model
      and the theory of planned behavior to identify determinants for targeting heart
      health interventions.
AB  - The theory of planned behavior and the stages-of-change model were used to gain a
      clearer understanding of the factors associated with regular exercise in order to
      plan more effective programs in heart disease prevention. The study was conducted
      using a self-administered postal questionnaire sent to a sample of 2,269 men 30
      to 60 years of age. Nearly a quarter (23.3%) of respondents were physically
      inactive, of whom 10.5% were in the precontemplation and 12.8% in the
      contemplation stages; 42.1% exercised less than twice a week, of whom 22.4% were
      in the preparation I and 19.7% in the preparation II stages. Only 34.6% were in
      the action stage, exercising regularly for at least 20 minutes twice a week or
      more with the intention of continuing to do so. Logistic regression indicated
      that the variables derived from the theory of planned behavior, namely attitude,
      subjective norm and perceived behavioral control, were differently associated
      with the stages of behavior. Perceived behavioral control was strongly
      significant in all stages. Attitude was related with stages in which individuals
      have intention of exercising (contemplation and preparation II). In contrast,
      subjective norm seemed to be associated with stages in which individuals have no
      intention of doing so (precontemplation and preparation I). By identifying the
      specific needs of sub-groups, the results can help define programs most likely to
      accelerate men to the stage of regular exercise, part of an effective strategy
      for heart health promotion in this high-risk population.

PMID- 9247848
TI  - Patient-physician pairing: does racial and ethnic congruity influence selection
      of a regular physician?
AB  - Many public and private sector efforts are devoted toward increasing the training
      of physicians from under-represented minority groups, yet little has been
      documented regarding the association between physicians' racial backgrounds and
      the patient populations they serve. To address this question, we use 1987
      National Medical Expenditure Survey to examine the impact of race/ethnicity on
      the matching between physician and patients. Our results show that minority
      patients are significantly more likely to report having a minority physician as
      their regular doctor. We estimate that minority patients are five times as likely
      as non-minorities to report that their regular physician is a member of a
      racial/ethnic minority. This effect is especially pronounced among Hispanics who
      identify a Hispanic physician as their regular provider 19 times more often than
      non-minorities. After controlling for other socioeconomic factors, both these
      figures remain significant, but drop by approximately one-half. These results
      support the notion that minority patients tend to see minority physicians at a
      disproportional rate independent of other socio-economic factors.

PMID- 9247849
TI  - Cancer coverage and tobacco advertising in African-American women's popular
      magazines.
AB  - Mass circulating magazines offer an opportunity to inform large segments of the
      population about preventive health behaviors relevant for cancer control. We
      collected information about the number and type of cancer articles from January
      1987 through December 1994 in Jet, Ebony and Essence magazines. These magazines
      each have a principal readership of African-American women and a paid circulation
      of 1,000,000 or more annually. Cancer articles were counted if the content was
      gender neutral or specifically targeted for women. There were 84 articles on
      cancer including 6 on lung cancer and 3 on other tobacco-related cancers. Nine
      additional references to lung cancer were mentioned under the general cancer
      category, but lung cancer was not the primary focus of the articles. There were
      24 articles on breast cancer and 9 on cervical cancer over the 8 year period.
      Most of the articles (> 70%) were short fillers of less than one page in length.
      A prevention focus was included in 42.2%, 75.0%, and 71.0% of the cancer articles
      in Jet, Ebony, and Essence respectively. Of the 649 health articles, 116 were on
      cardiovascular disease. In contrast, there were 1,477 tobacco advertisements over
      the 8 years. The number of cancer articles was not significantly associated with
      the number of tobacco advertisements. Because tobacco-related cancers are
      entirely preventable and contribute to the significant cancer burden, the lack of
      coverage of tobacco-related cancers is a missed opportunity for health promotion
      among African-American females.

PMID- 9247851
TI  - America's first medical malpractice crisis, 1835-1865.
AB  - Prior to the early 1800's, medical malpractice was almost unknown in the United
      States. However, a large number of malpractice law suits inundated the courts
      between 1835 and 1865. About 70 to 90 percent of the litigation involved
      fractures and dislocations with imperfect results or deformities such as
      shortened or crooked limbs. Lawyers alleged that the physicians did not provide
      due proper care, skill and diligence despite the fact that the better surgeons
      tried to save limbs rather than follow the common practice of amputation,
      especially for compound fractures. While a number of texts dealt with medical
      jurisprudence, it was not until 1860 that a text on the subject intensively
      delved into the issue of medical malpractice. Coincidentally, the attitudes and
      behaviors of patients, lawyers, physicians and judges during the first medical
      malpractice crisis were surprisingly similar to those currently held.

PMID- 9247850
TI  - Association between time homeless and perceived health status among the homeless
      in San Francisco.
AB  - The purpose of this study was to describe the perceived health of the homeless,
      and to measure the effect of time homeless on perceived health status, after
      controlling for sociodemographic characteristics and health conditions. The
      design was cross-sectional; the population was a representative sample of
      homeless in San Francisco, interviewed on health issues. Analysis of predictors
      of poor or fair health status was by logistic regression. In this sample of 2780
      persons, 37.4% reported that their health status was poor or fair as compared to
      good or excellent. Reporting poor or fair health status was significantly
      associated with time homeless, after controlling for sociodemographic variables
      and health problems including results from screening for HIV and TB (OR = 1.49,
      95% CI 1.24-1.79). Comparisons with data from the National Health Interview
      Survey (NHIS) showed poorer health status among the homeless persons in this
      study. Standardized morbidity ratios were highest for asthma; there was twice the
      number of homeless persons reporting asthma, in younger as well as older adults,
      as would be expected using NHIS rates. There was also an excess of arthritis,
      high blood pressure and diabetes in those age 18-44 as compared to adults in the
      Health Interview Survey. The time spent homeless remains associated with self
      reported health status, after known contributors to poor health are controlled.
      Persons who have been homeless for longer periods of time may be the persons to
      whom health care interventions should be aimed.

PMID- 9247852
TI  - Kinetic study of irreversible inhibition of an enzyme consumed in the reaction it
      catalyses. Application to the inhibition of the puromycin reaction by spiramycin
      and hydroxylamine.
AB  - A systematic procedure for the kinetic study of irreversible inhibition when the
      enzyme is consumed in the reaction which it catalyses, has been developed and
      analysed. Whereas in most reactions the enzymes are regenerated after each
      catalytic event and serve as reusable transacting effectors, in the consumed
      enzymes each catalytic center participates only once and there is no enzyme
      turnover. A systematic kinetic analysis of irreversible inhibition of these
      enzyme reactions is presented. Based on the algebraic criteria proposed in this
      work, it should be possible to evaluate either the mechanism of inhibition
      (complexing or non-complexing), or the type of inhibition (competitive, non
      competitive, uncompetitive, mixed non-competitive). In addition, all kinetic
      constants involved in each case could be calculated. An experimental application
      of this analysis is also presented, concerning peptide bond formation in vitro.
      Using the puromycin reaction, which is a model reaction for the study of peptide
      bond formation in vitro and which follows the same kinetic law as the enzymes
      under study, we have found that: (i) the antibiotic spiramycin inhibits the
      puromycin reaction as a competitive irreversible inhibitor in a one step
      mechanism with an association rate constant equal to 1.3 x 10(4) M-1 s-1 and,
      (ii) hydroxylamine inhibits the same reaction as an irreversible non-competitive
      inhibitor also in a one step mechanism with a rate constant equal to 1.6 x 10(-3)
      M-1 s-1.

PMID- 9247854
TI  - Kinetics of the thermal inactivation of alkaline phosphatase from green crab
      (Scylla serrata).
AB  - The kinetics of thermal inactivation of alkaline phosphatase from green crab
      (Scylla Serrata) has been studied using the kinetic method relating to the
      substrate reaction during irreversible inhibition of enzyme activity previously
      described by Tsou. The results show that the thermal inactivation of the enzyme
      is an irreversible reaction. Comparison of the microscopic rate constants for
      thermal inactivation of free enzyme and the enzyme-substrate complex shows that
      the presence of substrate has a certain protective effect against thermal
      inactivation.

PMID- 9247855
TI  - The effect of ultrasound on heme enzymes in aqueous solution.
AB  - The effect of cavitating 22 kHz ultrasound on aqueous solutions of hydrogen
      peroxide-consuming enzymes, catalase and peroxidases, both plant (horseradish
      peroxidase) and animal (lactoperoxidase) was studied. Catalase did not undergo
      inactivation during sonication, whereas activity of peroxidases decreased with
      increased duration of sonication. It is suggested, basing on the absorption
      spectra, that some conformational changes occur in peroxidases upon sonolysis. It
      is concluded from the experiments with free radical scavengers that partial
      enzyme inactivation and modification has not a chemical but a mechanical basis.

PMID- 9247853
TI  - Yeast hexokinase inhibitors designed from the 3-D enzyme structure rebuilding.
AB  - This work describes a search for hexokinase inhibitors based on the interactions
      analysis at the active site of the X-ray resolved o-tolulyl-glucosamine
      hexokinase (OTG-HK) complex structure. As the actual enzyme sequence was unknown
      when the X-ray structure was made (only 30% homology), the structure of the
      complex was rebuilt by modelling on the X-ray structure frame which allowed
      residues in close vicinity to the inhibitor to be defined, particularly Glu249
      and Gln278. Compounds with inhibitor-bearing groups able to interact with these
      residues were synthesized and assayed. Some of them revealed strong affinities,
      in the Km range for glucose. Kinetic analysis of their behaviour towards glucose
      and ATP together with spectroscopic studies using NMR, allowed the determination
      of the corresponding inhibition patterns and provided complementary information
      on HK.

PMID- 9247856
TI  - Modification of an essential amino group of glutathione reductase from yeast by
      pyridoxal 5'-phosphate.
AB  - Yeast glutathione reductase is inactivated by pyridoxal 5'-phosphate (PLP). The
      reactivation of the enzyme by dilution as well as a characteristic absorption
      peak at 325 nm exhibited by NaBH4-reduced-PLP modified enzyme show that the
      inactivation is due to the specific modification of the epsilon-amino group of
      lysine residue. The maximum of 70% inactivation was observed at 7mM PLP and the
      equilibrium was reached within 3 min. Kinetic and equilibrium analysis of
      inactivation data derived at different PLP concentrations showed that a
      noncovalent intermediate is formed prior to inactivation. From the studies on the
      effect of pH on the inactivation rate, the pKa of epsilon-amino group of the
      reactive lysine residue was calculated to be 7.3. Among various protecting agents
      tried, only NADP was found to be effective. The apparent stoichiometry of the
      reaction was one to one as the incorporation of 0.65 mole PLP/mole of enzyme led
      to 70% inactivation at saturating PLP concentration.

PMID- 9247857
TI  - Novel selective thiol inhibitors of neutral endopeptidase containing heterocycles
      at P'2 position.

PMID- 9247858
TI  - Rwanda 1994: a study of medical support in military humanitarian operations.
AB  - The deployment of British Contingent (BRITCON) to United Nations Force in Rwanda
      (UNAMIR) on Operation GABRIEL in 1994, proved to be a successful deployment on
      humanitarian operations. Many of the lessons have been successfully incorporated
      into training, equipment and organisational structures since the deployment.
      Others require further work to develop and assimilate. The essential issue
      concerning principles of humanitarian relief doctrine, mission definition,
      understanding the Disaster-Development continuum, capability mix, spectrum of
      military utility and the importance of force maintenance were all highlighted by
      the Rwanda deployment. Implications for future humanitarian operations include a
      co-operative approach to pre-deployment training with the Non-Governmental
      Organisation (NGO) community. This will help to promote understanding between the
      2 arms of the humanitarian effort and will exploit the strengths of both sides.
      Equally, the military medical services have to be fully aware of mission
      definition and its centrality to planning, execution and audit of performance.

PMID- 9247859
TI  - Medical planning--casualty treatment times at first and second line.
AB  - OBJECTIVE: To establish the average time taken to treat a seriously wounded
      battle casualty at First and Second Line (Role 1 and Role 2) according to the
      British Army Casualty Treatment Regimes under simulated conditions, and, in doing
      so, to assess whether British medical facilities are capable of meeting the
      medical planning directives of the Allied Command Europe Rapid Reaction Corps
      (ARRC). DESIGN: A casualty evacuation exercise, using standard ARRC medical
      planning data, deploying the war establishment of personnel and equipment of an
      armoured Battle Group Regimental Aid Post (RAP) and an armoured Field Ambulance.
      SUBJECTS: 200 simulated casualties, using 120 healthy soldiers dressed in
      expendable clothing and carrying a description of their injuries and clinical
      status. MAIN OUTCOME MEASURED: The time taken to treat simulated seriously
      wounded casualties at Role 1, the RAP and at Role 2, the Field Ambulance Dressing
      Station (DS). RESULTS: The mean treatment time at Role 1 was 28 minutes and at
      Role 2 was 17 minutes. CONCLUSION: Within the (large) caveat of simulation, as
      presently configured, the Field Ambulance (DS) is well able to cope with the
      casualty load expected of it by ARRC medical planners but the RAP of the armoured
      Battle Group is not.

PMID- 9247861
TI  - Army helicopter casualty evacuations in Belize in 1995 and 1996.
AB  - Since the withdrawal of Royal Air Force Puma helicopters from Belize in 1994, the
      role of casualty evacuation (CASEVAC) of British military personnel, Belizean
      citizens and foreign nationals throughout the country, has passed to 25 Flight
      Army Air Corps, currently equipped with Gazelle helicopters. Details of casualty
      evacuations during 1995 and 1996 have been collated and analysed in order to
      provide information on casualty types, and the locations from which casualties
      have been evacuated, during this 2 year period. The data so obtained might be
      used to ensure the future provision of an appropriately equipped CASEVAC
      helicopter, or to highlight common causes of significant morbidity in British
      troops deployed to Belize.

PMID- 9247860
TI  - Orthopaedic casualty evacuation to the Royal Hospital Haslar November 1995 to
      April 1996.
AB  - A survey of the orthopaedic casualties evacuated (casevacs) to the Royal Hospital
      Haslar between November 1995 and April 1996 was performed. A total of 464 service
      persons and civilians were casevaced. Orthopaedic cases amounted to 55% of all
      evacuations. Of these, 54% were British Army personnel. Conditions necessitating
      casevac were classified as either acute, (occurring during the deployment), or
      chronic (where the condition was present prior to deployment). Of the acute
      cases, there was an even mix between bony and soft tissue injuries (STIs).
      Sporting activities were the commonest cause of injury. The condition had been
      present prior to deployment in 16% of cases. Half of these were considered to
      have been unfit for deployment. Strategies for prevention of unnecessary casevacs
      are discussed.

PMID- 9247862
TI  - Hodgkin's disease in Army personnel 1977-1987.
AB  - A retrospective review of all British Army patients presenting to the Queen
      Elizabeth Military Hospital with a diagnosis of Hodgkin's disease between 1977
      and 1987 was performed, with a minimum follow-up of 7 years. The results were
      similar to those reported in other (similar) series, and the changes in
      investigations and treatment observed during this period matched those occurring
      in wider clinical practice through close co-operation with a recognised Cancer
      Centre. Despite their comparative rarity, Army patients with Hodgkin's disease
      receive modern, effective treatment.

PMID- 9247863
TI  - Prevalence of inguinal hernia in otherwise healthy males of 20 to 22 years of
      age.
AB  - Twenty-seven thousand four hundred and eight adult males between 20 and 22 years
      of age who were otherwise healthy were examined to detect inguinal hernias. Eight
      hundred and eighty-five (3.2%) inguinal hernia cases were detected. These were
      479 (54.1%) right inguinal hernias, 351 (39.7%) left inguinal hernias and 55
      (6.2%) bilateral inguinal hernias. One hundred and eighty-five (20.9%) subjects
      reported first degree relatives and 147 (16.6%) subjects reported second degree
      relatives with inguinal hernias. It is concluded that these results may be a
      useful guide for future studies about the prevalence of inguinal hernias in the
      populations as a whole and suggest a familial predisposition.

PMID- 9247864
TI  - Mental health problems on Operation Resolute (Bosnia).
AB  - Mental health problems have been studied in a total of 2201 consultations with
      British troops in a primary health care practice on Operation Resolute (Bosnia)
      from 1 January to 31 March 1996. About one in 40 (2.5%) of the consultations were
      for mental health problems; Post Traumatic Stress Disorder (PTSD), depressive
      disorder, and grief reaction were the most common disorders, followed by acute
      adjustment reaction and panic disorder. Most cases pre-dated deployment. The
      number of cases repatriated to the UK was 17, about 10% of the total number of
      patients repatriated from theatre in this period.

PMID- 9247865
TI  - Societal factors that negatively affect the mental health support for the British
      Army's Service personnel involved in major trauma.

PMID- 9247866
TI  - Penetrating cranio-cerebral injuries.
AB  - The modern soldier, as with his predecessors, remains at risk from penetrating
      cranio-cerebral injury. The subject is briefly reviewed and the modern approach
      outlined in a military context.

PMID- 9247868
TI  - Training related left ventricular hypertrophy in a soldier.

PMID- 9247867
TI  - Sterile abscess formation following plague vaccination.
AB  - As part of the immunisation programme of servicemen on OP Granby, deployed in the
      Gulf, plague vaccine was recommended as a prophylaxis. Out of a total of 524
      vaccinations at our location, one sterile abscess formation was noted. The case
      report is described.

PMID- 9247869
TI  - Helicopter main rotor blade injury to the head with survival.

PMID- 9247870
TI  - The "very long hiccup" and the emergence of the Army Medical Services in Malta.
AB  - The link between the Maltese islands and the Army Medical Services was forged
      during the Wars of Revolutionary France, 1792 to 1802. This article looks at the
      two-year long blockade of the French garrison in Malta, Nelson's so called "very
      long hiccup" (1), and at the origins of the Army Medical Services in the Maltese
      islands.

PMID- 9247871
TI  - Battlefield analgesia.

PMID- 9247872
TI  - Shattered illusions--the Thiepval barracks bombing.

PMID- 9247873
TI  - Biological implications of magnesium salts at the molecular level.
AB  - The interaction of Mg2+ cations in biological systems is studied by using nucleic
      acid bases as the biological system. Magnesium salts, such as, MgCl2 6H2O, MgSO4.
      7H2O and Mg(ClO4). XH2O have been employed in order to compare their complexation
      with cytosine and 1-methyl cytosine crystallize in water solutions. The reaction
      of the above magnesium salts with the two bases has been followed by attempting
      to crystallization the complexes formed at constant temperature and variable
      times of crystallization. The water solutions with the above reagents have also
      been followed by Fourier Transform infrared.

PMID- 9247875
TI  - Cholesterol metabolism in human umbilical arterial endothelial cells cultured in
      low magnesium media.
AB  - To study the time- and dose-dependent effects of low magnesium on free
      [H3]cholesterol uptake, [H3]mevalonolactone incorporation into cholesterol, and
      both of which labelled precursors and [H3]oleic acid incorporations into
      cholesteryl esters, cultured human umbilical arterial endothelial cells were
      exposed to experimental media containing decreasing magnesium concentrations at
      94, 188, 376 and 564 microM until 48 h. A level of magnesium at 949 microM was
      used as a control. The results showed that reduced magnesium in the cultured
      medium led to a decrease in [H3]cholesterol, uptake, an inhibition of the
      incorporation of [H3]mevalonolactone into cholesterol and a stimulation of the
      incorporation of [H3]cholesterol, [H3]mevalonolactone and [H3]oleic acid into
      cholesteryl esters, but the time- and dose-dependent effects of magnesium
      deficiency were not significant. We suggest that reduced cholesterol uptake and
      synthesis might contribute to hypercholesterolaemia under a condition of
      magnesium deficiency, and that enhanced cholesterol esterification might be
      explained by a stimulated activity of acyl-Coenzyme A: cholesterol O
      acyltransferase (ACAT).

PMID- 9247876
TI  - Reversible model of magnesium depletion induced by systemic kainic acid injection
      in magnesium-deficient rats: I--Comparative study of various magnesium salts.
AB  - We developed three models of reversible magnesium depletion in rats resulting
      from the combined effects of kainic (KA) acid with magnesium deficiency, in order
      to compare the effects of various common magnesium salts (pidolate, aspartate,
      lactate, gluconate and chloride) and of magnesium acetyl taurinate (MgATa),
      administered daily (14 mg Mg2+, PO) for ten days. First, the immediate effects
      (wet dog shakes, clonic convulsions and death 1 h after injection) and late
      effects (fall from hole board between the second and tenth days post injection)
      of kainic acid at three different doses (3.6 and 11 mg/kg) were studied in
      magnesium deficient rats (50 ppm for 40 days) and in non-deficient rats (1700
      ppm). The results showed that the effects of kainic acid were enhanced in
      magnesium deficient rats. Secondly, after ten days of physiological then
      pharmacological doses of magnesium, used as chronical supplementation, we showed
      that kainic acid administration combined with magnesium deficiency led to
      magnesium depletion of increasing severity depending on the dose of kainic acid.
      The observed magnesium depletions were weak at a dose of 3 mg/kg KA, moderate at
      a dose of 6 mg/kg and severe at a dose of 11 mg/kg. These depletions were more or
      less reversible, and this enabled the classification of the therapeutic effects
      of these salts on Mg depletion. Among common salts, magnesium pidolate presented
      the greatest efficacy but none of them fully prevented depletion. In contrast,
      MgATa was efficient on all the aspects of depletion, when administered
      preventively both chronically or acutely or as a single curative injection.
      Consequently the results we obtained in the present study, on a new model of
      magnesium depletion, showed the greatest efficacy of magnesium acetyl taurinate
      we demonstrated yet on other models of reversible magnesium depletion.

PMID- 9247874
TI  - Effects of the application of aluminium, strontium and magnesium solutions to the
      leaf surface of maize, and determinations of these elements by ICP-AES.
AB  - The uptakes of aluminium, magnesium and strontium through maize leaves were
      investigated. The plants were grown in the light and in the dark (etiolation).
      Samples of leaves were digested with a mixture of nitric acid and hydrogen
      peroxide, and measurements were made by ICP-AES. The aluminium, magnesium and
      strontium contents of control samples grown in the light or in the dark were
      found to be similar. There were significant increases in the contents of these
      elements after maize leaves were sprayed with aluminium, magnesium or strontium
      solutions: increases of 100 per cent for aluminium, 20 per cent for magnesium and
      10 per cent for strontium. The uptakes of these elements were generally higher in
      the light than in the dark. Aluminium, magnesium and strontium ions act as
      antagonists of each other. The effects of spraying with the different solutions
      were also observed in the colour of the maize leaves. However, the ultrastructure
      of the leaves did not change. The formation of chlorophyll was accelerated by
      magnesium, and inhibited by aluminium or strontium.

PMID- 9247877
TI  - Intravenous magnesium load test in elderly patients with protein-energy
      malnutrition.
AB  - Forty-two elderly patients were subjected to a nutritional assessment and an
      intravenous magnesium load (0.5 mmol/kg). After 48 h, patients with protein
      calorie malnutrition (PCM) showed magnesium retentions (MgR) above 20 per cent,
      thus indicating magnesium deficit, and greater (P < 0.001) than those from well
      nourished patients. The discriminating cross-point for undernourished patients
      was at 28 per cent with 95 per cent sensibility and specificity. There were
      significant correlations between MgR and most nutritional parameters. An increase
      of the RMg constitutes a PCM indicator which may be useful to quantify it.

PMID- 9247878
TI  - Magnesium and antioxidant vitamin status and risk of complications of ageing in
      an elderly urban population.
AB  - This cross-sectional survey was conducted in 20 randomly selected streets in
      Moradbad city in North India to determine the association of magnesium and
      antioxidant vitamins with risk of ageing. There were 595 subjects (314 males, 281
      females) between 50-84 years of age inclusive. The overall prevalence of hypo
      magnesemia was 11.8 per cent (n = 60) with a prevalence of 13.2 per cent (n = 33)
      in males and 10.6 per cent (n = 27) in females. The prevalence of hypomagnesemia
      showed significant declining trend in the concentration of serum magnesium,
      vitamin C, vitamin E and beta-carotene and a rising trend in lipid peroxides and
      diene conjugates with increase in age from 50-59 years to 70-84 years in both men
      and women. Multivariate logistic regression analysis showed that serum magnesium,
      vitamin C, vitamin E and beta-carotene were significant risk factors of ageing in
      both men and women. The findings suggest that some urban populations of India can
      benefit by consuming higher dietary magnesium, potassium and antioxidant vitamins
      for prevention of ageing.

PMID- 9247879
TI  - Altered platelet magnesium and plasma and urinary soluble form of intercellular
      adhesion molecule I (sICAM-1) concentrations in insulin dependent diabetes
      mellitus (IDDM) patients with microalbuminuria.
AB  - Magnesium concentrations in plasma, erythrocyte and platelet, and plasma and
      urine levels of the soluble form of Intercellular Adhesion Molecule-1 (sICAM-1)
      were evaluated in subjects with insulin dependent diabetes mellitus (IDDM) with
      or without microalbuminuria, and in a control group of healthy subjects. Using a
      recently introduced technique, we found that magnesium concentrations in
      platelets in diabetic subjects with microalbuminuria were lower than in diabetics
      with normal albuminuria (1.859 +/- 0.47 vs 2.065 +/- 0.62 mumol/10(8) cells; P <
      0.05). Moreover, IDDM subjects had higher plasma sICAM-1 levels than control
      subjects; no difference, however, was found between sICAM-1 concentrations in the
      two groups of diabetics. An inverse correlation was found between intraplatelet
      magnesium and plasma sICAM-1 levels (r = - 0.64; P < 0.05) in the diabetics with
      microalbuminuria. It is concluded that the reduced intraplatelet magnesium
      content may contribute to the progression of the vascular complications in IDDM
      subjects with microalbuminuria.

PMID- 9247880
TI  - Protein peroxidation, magnesium deficiency and fibromyalgia.
AB  - Lipid and protein peroxidations were investigated in female patients with
      magnesium deficit (MD), fibromyalgia (FM) and age matched controls:
      malondialdehyde and protein carbonyls (PC), as well as serum, leucocyte and
      erythrocyte magnesium (EMg) were assessed in 20 controls, 25 FM and 16 MD
      patients. MDA are unchanged in MD and FM. PC are significantly increased (P <
      0.01) in FM. EMg is significantly decreased in MD. There is a slight, but not
      significant, negative correlation between PC and EMg, in controls and MD. Protein
      peroxidations are demonstrated in FM. Further studies are needed in MD.

PMID- 9247881
TI  - Neuromodulation by Mg2+ and polyamines of excitatory amino acid currents in
      rodent neurones in culture.
AB  - Excitatory amino-acid currents in rodent central neurones are mediated by the
      activation of glutamate receptors. Ionotropic types of the receptors are divided
      into alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N
      methyl-D-aspartate (NMDA) receptors, and the former two are collectively called
      non-NMDA receptors. The NMDA receptor is modulated by a number of endogenous
      neuromodulators including Mg2+, polyamines, glycine and protons in extracellular
      solutions. Although it has been generally thought that each of the
      neuromodulators acts on a distinct site in the NMDA receptor, recent studies have
      revealed that these actions may be not necessarily independent of each other. The
      NMDA receptor response is not only inhibited but also potentiated by Mg2+, and
      the latter action is due to an interaction of a Mg2+ site with either glycine- or
      proton-binding site. In the presence of polyamines, a tonic inhibition by protons
      of the NMDA receptor response is relieved, resulting in a potentiation of the
      response. Alternatively, it has been recently revealed that there are some
      subtypes of non-NMDA receptors which are negatively modulated by polyamines in
      either extra- or intra cellular solutions. The difference in polyamine
      sensitivity among non-NMDA receptors is attributed to a distinction in their
      constituted subunits. The inhibition of non-NMDA receptor by intracellular
      polyamines results in inward rectification of the current-voltage relation which
      is not seen for polyamine-insensitive ones. This polyamine action is not mimicked
      by intracellular Mg2+.

PMID- 9247882
TI  - Commentary on magnesium deficiency and nitric oxide.

PMID- 9247883
TI  - Commentary on magnesium deficiency, substance P receptor up-regulation and NO
      overproduction.

PMID- 9247884
TI  - Dairy products and breast cancer: the IGF-I, estrogen, and bGH hypothesis.
AB  - Research on the role of dietary factors in breast cancer causation has focused
      predominantly on fat intake. While some studies have examined associations
      between breast cancer rates and consumption of whole milk, there has been less
      attention given to dairy products in general. Dairy products contain both
      hormones and growth factors, in addition to fat and various chemical
      contaminants, that have been implicated in the proliferation of human breast
      cancer cells. This literature review evaluates the epidemiological and
      mechanistic evidence linking dairy consumption with breast cancer risk.

PMID- 9247885
TI  - Identification of cytotoxic peptide as possible mechanism for neurotoxicity of
      HIV viral envelope and AIDS pathogenesis.
AB  - A major segment of acquired immunodeficiency syndrome (AIDS) patients suffer from
      neurological complications, including impairments in concentration and motor
      functions. This neuronal injury, although related to the human immunodeficiency
      virus (HIV), occurs even though the neurons themselves are not infected by the
      virus. A complex web of interactions of the immune system with noxious substances
      released from gp120-stimulated macrophages is hypothesized as the mechanism of
      the injury. This study has identified an antimicrobial peptide resident in the
      human small intestine as a candidate for these noxious substances. This peptide
      is neither cell nor tumor specific and mediates cytolysis by membrane
      permeabilization based on membrane potential. The identified peptide is, however,
      type specific against viruses, only attacking enveloped viruses. This study
      hypothesizes that the peptide is sequestered in the HIV viral envelope and is
      released in very toxic concentrations when localized membrane potential is high.
      The peptide is localized in the Paneth cells of the human small intestine, and a
      transmission pathway is identified through the abrogation of intestinal tissue
      occurring during receptive anal intercourse. A study of amino acid sequences
      between this peptide and three variants of HIV confirmed homologies. The
      identification of this peptide as a possible mechanism could substantially alter
      AIDS treatment protocols.

PMID- 9247886
TI  - Red cell age by flow cytometry.
AB  - A method is presented for the use of red cell markers to assess the age of red
      cells in clinical samples. The reticulocyte count and its variants are already in
      clinical use to measure the number of young circulating red cells, but tools have
      not been put into place for studying the overall distribution of red cell age.
      These data could be of significant value, not merely for hematologic
      investigations, but as a part of infectious disease, renal, and toxicologic
      studies.

PMID- 9247887
TI  - Does excessive adenosine 5'-triphosphate formation in cells lead to malignancy? A
      hypothesis on cancer.
AB  - In biological systems, adenosine triphosphate (ATP) is the principal contributor
      of free energy necessary for anabolic reactions and is also a precursor of
      nucleic acids. Moreover, active transport of metabolites into cells is also
      driven by hydrolysis of ATP. So, a cell may grow, multiply and ultimately turn
      malignant when it has been transformed in such a manner that it produces excess
      ATP as compared with its usual metabolic demand. Recent studies have indicated
      that mitochondrial complex I and the glycolytic enzyme glyceraldehyde 3-phosphate
      dehydrogenase (GA3PD) may be critically altered specifically in malignant cells.
      So, we further propose that this excessive ATP formation may be due to altered
      mitochondrial complex I and GA3PD of malignant cells.

PMID- 9247888
TI  - Total abrogation of facial seborrhoeic dermatitis with extremely low-frequency (1
      1.1 Hz) 'imprinted' water is not allergen or hapten dependent: a new visible
      model for homoeopathy.
AB  - Extremely low frequencies, from 1 to 1.1 Hz, imprinted in water (imprinting was
      done by succussing a glass containing the water) led to a total abrogation of a
      facial seborrhoeic dermatitis, previously proposed as a visible model for the
      theory of 'memory of water'. This technique provides a new perspective on the
      enigma of homoeopathy and the treatment of allergic diseases and possibly all
      other inflammatory reactions.

PMID- 9247889
TI  - Fish lipids: more than n-3 fatty acids?
AB  - Recent studies have shown that marine oils rich in long-chain (C20 and C22) fatty
      acids (i.e. certain natural marine oils and partially hydrogenated fish oil) may
      affect the haemostatic balance in a favourable way with regard to coronary heart
      disease. Such fats have also been found to increase the content of EPA
      (eicosapentaenoic acid = C20:5 n-3) and to decrease the content of arachidonic
      acid (C20:4 n-6) in blood lipids, thus affecting the ratio of C20:4 n-6 to C20:5
      n-3 in a favourable way with regard to eicosanoid production. It is therefore
      likely that the positive effects of long-chain monoenoic fatty acids on
      haemostasis are due to increased synthesis of long-chain essential n-3 fatty
      acids. According to recent theories the final steps in the synthesis of long
      chain essential fatty acids occur in the peroxisomes, which also have a
      controlling function in essential fatty acid synthesis. Long-chain monoenoic
      fatty acids are known to enhance peroxisomal beta-oxidation. An hypothesis is
      therefore advanced that marine oils rich in long-chain monoenoic fatty acids
      improve haemostasis in a favourable way with regard to coronary heart disease
      through increased peroxisomal beta-oxidation and increased synthesis of long
      chain n-3 fatty acids.

PMID- 9247890
TI  - Reporting levels of spinal blockade.
AB  - With spinal anesthesia the level of surgical analgesia is mostly reported without
      reference to the neuroanatomic map of spinal nerves. The classical maps are
      variably and inconsistently reported in many textbooks. Because of the
      differences between the classical maps of Keegan and Garrett and of Foerster, and
      also because of the variability in their interpretation, we applied them to the
      same clinical data. This resulted in a theoretically clinically significant
      difference of two segments. It is concluded that clear reference should be made
      to the implemented segmental map in expressing the level of spinal blockade.

PMID- 9247891
TI  - Cure or control of HIV/AIDS?

PMID- 9247892
TI  - Is breast cancer caused by late exposure to a common virus?
AB  - Although there are recognized risk factors for breast cancer, its cause is still
      unknown. It is hypothesized here that breast cancer results from late exposure to
      a common virus. This hypothesis is investigated by relating the epidemiology of
      breast cancer to the seroepidemiology of cytomegalovirus, as a surrogate for a
      breast cancer virus. The hypothesis is consistent with the geographical
      distribution of breast cancer; a correlation between breast cancer incidence and
      the percentage of adults who are cytomegalovirus seropositive in various
      countries was found (Pearson correlation coefficient -0.79). The hypothesis is
      also consistent with other risk factors for breast cancer, such as age at onset,
      family history, hormonal factors and migration.

PMID- 9247893
TI  - Evolution's 'missing link': a hypothesis upon neural plasticity, prefrontal
      working memory and the origins of modern cognition.
AB  - Many activities such as reading, mathematics and chess depend upon cognitive
      processes which arose after our evolution. Why could they arise if not evolved? I
      argue four things fortuitously came together to make our nonevolved cognitive
      skills possible: (i) neural plasticity; (ii) large functionally uncommitted
      prefrontal, temporal and parietal cerebral cortices; (iii) the ability of their
      neural circuits (due to neural plasticity), if trained, to take on novel symbolic
      and nonsymbolic skills; and (iv) a large prefrontal cortex which could use its
      working memory as a tuition management sketch pad in which to train them. Pre
      evolved for other reasons, these four (together with invented symbolic systems
      and technology) together enable modern humans to 'upgrade' our already evolved
      cognitive skills to do new and nonevolved things.

PMID- 9247894
TI  - The elusive local factor in atherosclerosis.
AB  - Recent evidence confirms that local haemodynamic stresses account for the
      initiation, topographical localization and complications of atherosclerosis.
      These causative stresses are vibratory and associated with pulse pressure and the
      lesser vibrations of greater frequency generated by blood flow at predilection
      sites. This bioengineering fatigue hypothesis is further substantiated by
      analogous effects of repetitive stresses on erythrocytes and in the
      musculoskeletal system. The mechanism underlying fatigue is cumulative molecular
      scissions of the mural constituents which ultimately result in failure of the
      wall as a whole. Free radicals and oxidation products are by-products of this
      molecular scission in atherogenesis. This theory which explains the progressive
      inexorable loss of mural cohesion, its pathogenesis and complications is
      completely substantiated by the iatrogenic and experimental reproduction of the
      disease by haemodynamic means.

PMID- 9247895
TI  - Bartonellosis and human immunodeficiency disease (AIDS): L-forms as persisters,
      activating factors, and mechanism of disease.
AB  - Bartonella, genus Proteus, can cause immunodepressive disease. The organisms, in
      parasitized red blood cells, may invade the brain and every other system and
      space in the human body. Bartonella henselae is proposed to have a role in the
      pathogenesis of acquired immunodeficiency syndrome (AIDS) encephalopathy.
      Bartonella bacilliformis produces two known toxins that can induce spasm and
      angiomatosis, respectively, and manifest as diseases associated with symptomatic
      AIDS. The skin lesions of bartonellosis may be mistaken clinically and
      histologically for Kaposi's sarcoma. Bacteria of the genus Proteus produce L
      forms: their elementary bodies may be mistaken for what are called the 'human
      immunodeficiency viruses' (HIV). Antibiotics, especially penicillin, induce
      bacteria to produce L-forms. Air pollution and high sugar, salt and fat diets are
      factors that may increase the lipid content of microbes that produce toxins and L
      forms that may persist or revert to bacterial form.

PMID- 9247896
TI  - The viral envelope in the evolution of HIV: a hypothetical approach to inducing
      an effective immune response to the virus.
AB  - The human immunodeficiency virus (HIV) is 'perceived' by the host immune system
      as partly-self because of the presence of host cell wall membrane on the viral
      envelope. This perception leads to an ineffective immune response to the virus.
      It is proposed that only viral core antigens without the envelope will be
      perceived as non-self by the host immune system and can provoke an effective
      immune response. In normal uninfected persons, core antigens could therefore
      serve as a vaccine. In HIV infected persons, uncommitted immunocytes from the
      peripheral leucocytes freed from antibodies will in vitro process autologous
      viral core antigens as non-self antigens and lead to an effective immune response
      against the HIV when reinjected into the patient. The use of autologous viral
      core antigens provides, at the same time, a means for testing viral core antigens
      as possible vaccines without any risk to a third person. This immunotherapy of
      the HIV, when confirmed, will support core antigens as possible vaccines and
      could also be applied to the large group of retroviral and other enveloped
      viruses that cause chronic infections and malignant tumours in man and animals,
      with considerable benefits to human and animal health.

PMID- 9247897
TI  - Melatonin in osteosarcoma: an effective drug?
AB  - The pineal indole amine melatonin has been shown to have oncostatic properties in
      a wide variety of neoplasms. Melatonin levels start to diminish before the onset
      of puberty and continue to decline during puberty. There appears to be a
      relationship between the rate of bone growth and the incidence of osteosarcoma
      (which was found to be highest in the long bones of the leg in the 10-14-year age
      group). It is hypothesized that the simultaneous decrease in melatonin levels
      (with diminishing oncostatic protection), concurrent with the exponential
      increase in bone growth during puberty (i.e. increased rate of cell
      proliferation), could be a factor in the typical age distribution of
      osteosarcoma. Melatonin is of value in combined chemotherapy, because it is non
      toxic and can augment the anti-cancer action and decrease the side-effects of
      many other chemotherapeutic drugs. It is hoped that melatonin, as an adjunct to
      the routine chemotherapy of osteosarcoma, will help to improve the prognosis of
      this too often fatal disease.

PMID- 9247898
TI  - The Maginot Line and AIDS vaccines.
AB  - Despite extensive and costly efforts, attempts to develop a vaccine against human
      immunodeficiency virus (HIV), the causative agent of the acquired
      immunodeficiency syndrome (AIDS), have been unsuccessful. Using the Maginot Line
      as a metaphor, we discuss the reasons why an antibody-based vaccine strategy
      against HIV has failed. The concept of a vaccine that exclusively promotes cell
      mediated immunity against the virus is outlined, and important factors in the
      formulation of this novel vaccine are delineated. In particular, vaccine
      adjuvants and HIV peptides that elicit a cell-mediated immune response are
      crucial components of this immunization strategy. Examination of primate immune
      systems that resist retroviral pathogenicity will also play an important role in
      the development of a successful AIDS vaccine.

PMID- 9247899
TI  - A hypothesis that aging results from defects in genetically produced proteins.
AB  - The hypothesis is presented that our life span is genetically programmed and that
      it is possible that a defect in produced proteins encoded by the 'longevity' gene
      is a cause of aging. A study of correlations between defective enzyme activity in
      two diseases characterized by premature aging (progeria and Werner's syndrome)
      could assist in elucidating the common mechanism for all aging processes.

PMID- 9247900
TI  - Zinc-controlled Th1/Th2 switch significantly determines development of diseases.
AB  - Functional, excessive-possibly temporary-deficiencies of the trace element zinc
      can change immune functions prematurely from predominantly cellular Th1 responses
      to humoral Th2 responses. T helper (Th1) cells produce cytokines such as
      interleukin-2 (IL-2) and interferon gamma, thereby controlling viral infections
      and other intracellular pathogens more effectively than Th2 responses through
      cytokines such as IL-4, IL-5, IL-6 and IL-10. The accelerated shift from the
      production of extra Th1 cells during these cellular immune activities to more Th2
      cells with their predominantly humoral immune functions, caused by such a zinc
      deficiency, adversely influences the course of diseases such as leprosy,
      schistosomiasis, leishmaniasis and AIDS, and can result in allergies. It is
      noteworthy that AIDS viruses (HIVs) do not replicate in Th1 cells, which probably
      contain more zinc, but preferentially in the Th0 and Th2 cells; all the more so,
      because zinc and copper ions are known to inhibit intracellular HIV replication.
      Considering the above Th1/Th2 switch, real prospects seem to be offered of
      vaccination against such parasites as Leishmania and against HIVs.

PMID- 9247901
TI  - The omnipotent platelet. Part II: Further observations.
AB  - Observation of platelet responses during acute injury or pathology can provide
      important information. The initial response is thrombocytopenia followed by
      thrombocytosis. In the case of injury with negative X-ray and appropriate
      thrombocytosis, a bone scan is indicated. The platelet responds like a
      sedimentation rate, which indicates the course of the injury or pathology.

PMID- 9247902
TI  - Sporadic apnea: paradoxical transformation to eupnea by perturbations that
      inhibit inspiration.
AB  - We speculate that sporadic apneas may be initiated and terminated by stochastic
      neural perturbations arising within or impinging upon the respiratory oscillator.
      A curious situation can then arise in which tiny perturbations that inhibit
      inspiration, paradoxically stimulate breathing. The plausibility of the
      hypothesis is supported by numerical analysis of a noisy attractor-cycle
      oscillator, and in studies of a preterm sleeping infant with sporadic apnea; low
      level vibratory stimulation transformed the irregular apneic rhythm to eupnea.

PMID- 9247904
TI  - Effects of natural and man-made electric/electromagnetic fields on human health:
      a possible mechanism.
AB  - Studies and observations have shown that natural and artificial
      electric/electromagnetic fields affect human health. The author suggests that
      these fields can alter the state of acupuncture points, and produce an
      acupuncture-like effect. The author further suggests that the influence of
      natural and man-made electric/electromagnetic fields on human health is mediated
      by electrical processes in acupuncture points.

PMID- 9247903
TI  - Observations on sleeping position and essential hypertension.
AB  - A hypertensive black male, at risk for episodic attacks of pseudo-malignant
      hypertension and self-induced atrial fibrillation, seeks to discover possible
      clues to the pathogeneses of these strange disorders through self-study and
      concludes they might be associated with impaired oxygen intake, secondary to
      sleeping position in bed.

PMID- 9247905
TI  - Human immunodeficiency virus-1 proviral gene disruption by targeted gene therapy:
      a hypothetical technique for the elimination of provirus from the infected cells.
AB  - A hypothetical technique is proposed for the elimination of all the integrated
      human immunodeficiency virus-1 provirus from infected cells, based on the
      developing technology of selective gene excision through homologous
      recombination. In this technique, a recombinant retroviral packaging cell-line
      which would produce integrase-Rep78 chimeric protein would be constructed.
      Replication defective viral stocks would be made from this system which would
      have recombinant integrase-Rep78 protein packaged along with human
      immunodeficiency virus-1 long terminal repeat DNA. Since the Rep78 protein, which
      is a major regulatory protein of adeno-associated virus, has high affinity for
      human immunodeficiency virus-1 long terminal repeat, it would tether the newly
      synthesized human immunodeficiency virus-1 long terminal repeat (therapeutic DNA)
      to the human immunodeficiency virus-1 proviral site in the infected cell. This
      newly reverse transcribed human immunodeficiency virus-1 long terminal repeat
      would undergo homologous recombination with the provirus in the infected cells,
      facilitated by the nicking of the integrase part of the integrase-Rep78
      recombinant protein. This selective gene knockout would be accomplished by the
      combined action of the chimeric integrase-Rep78 protein, where the Rep78 part
      would help docking of the therapeutic DNA to the proviral integration site and
      the integrase would provide nicking activity after homologous recombination,
      resulting in the replacement of human immunodeficiency virus-1 proviral genome
      with therapeutic DNA.

PMID- 9247906
TI  - Major histocompatibility complex as an antigen pump: self-declaration in somatic
      cell society.
AB  - Self-recognition by the immune system is a basic mechanism of vertebrates.
      Mechanisms of antigen presentation by somatic cells are based on the coupling of
      small peptides produced in cytoplasm and major histocompatibility complex major
      histocompatibility complex. The antigen pumps, including major histocompatibility
      complex, can present various internal molecules which are possible targets of
      autoimmunity, using a peptide binding mechanism. The antigen pump can transfer
      external signals by autoantibody and cellular immunity without a specific
      receptor system. This self-declaration mechanism continuously presents 'self'
      rather than 'non-self'. It is qualitatively impossible to differentiate self
      antigens from non-self antigens in this process at all. Somatic cell society is
      non-self for germ line DNA, since germ line DNA is symbiotic with somatic cell
      society. Consequently, non-self can be recognized through self-declaration.

PMID- 9247907
TI  - Trivalent chromium and the diabetes prevention program.
AB  - The Diabetes Prevention Program is a new, 150 million dollar, NIH-sponsored study
      designed to determine whether non-insulin-dependent diabetes mellitus can be
      prevented or delayed in persons with impaired glucose tolerance. Four thousand
      subjects will be randomly assigned to one of four study groups and followed for
      4.5 years. Study groups include intensive lifestyle intervention with diet and
      exercise; metformin (Glucophage) or troglitazone (an investigational drug) with
      standard diet and exercise; and a control group. Insulin resistance is an
      important pathogenic factor in impaired glucose tolerance. Trivalent chromium, a
      dietary supplement that potentiates the action of insulin, was not included in
      the program. Like metformin and troglitazone, trivalent chromium decreases
      insulin resistance and has an acceptable side-effect profile; furthermore, it is
      available at a fraction of their cost. Trivalent chromium should have been
      included in the Diabetes Prevention Program; it is unfortunate that it was
      omitted.

PMID- 9247908
TI  - Natural steroids counteracting some actions of putative depressogenic steroids on
      the central nervous system: potential therapeutic benefits.
AB  - Psychological similarities in the symptomatology of Cushing's and depressive
      diseases led to repeated attempts of treatment of the affective disease by
      suppression of adrenocortical secretion. While successful in many patients, all
      drugs employed-metyrapone, ketoconazole and aminoglutethimide-carry the danger of
      inducing adrenal insufficiency. In addition, their undesirable side effects were
      also a main reason for treatment suspension. In our 1990 proposal for the
      treatment of depression through control of adrenal steroid levels, we set as one
      of the goals the identification of steroids which can antagonize each other on
      their effects on the central nervous system. Specifically, we looked first at
      steroids that could counter each other's effects on long-term potentiation, a
      putative memory mechanism in the central nervous system. One reason for this was
      the consensus that memory mechanisms are affected in both Cushing's and
      depressive patients. Another was the fact that cortisol-type hormones which
      underlie, at least in part, the depressogenic actions of adrenal steroids also
      have inhibitory effects on LTP. We conjectured, then, that a steroid with
      opposite effects, one that could enhance long-term potentiation and, further,
      that could counter the depressant effects of corticosterone on long-term
      potentiation, could be of use in the treatment of depression.
      Dehydroepiandrosterone sulfate increases long-term potentiation in a dose-related
      manner, and preliminary data suggest that it also counteracts the depressant
      effects of corticosterone on long-term potentiation when injected simultaneously
      on experimental animals. Potentially at least, rather than resort to total
      suppression of adrenocortical activity, it may be possible to treat depression
      just by counteracting some of the effects of cortisol-like hormone actions in the
      central nervous system. Further, both in clinical trials as well as in
      experimental animals, dehydroepiandro-sterone sulfate has been shown to enhance
      performance in memory-requiring tasks.

PMID- 9247909
TI  - Does urokinase play a role in renal stone formation?
AB  - Renal stone formation is a complex multifactorial disease, and it is believed
      that the initial step in the pathogenesis of urolithiasis must be the
      precipitation of an organic matrix of mucoproteins followed by precipitation of
      minerals onto this matrix. An important factor in this process may be the
      activity and/or concentration of the urinary enzyme, urokinase, which would
      affect the level of urinary mucoproteins such as uromucoid. In support of this
      hypothesis, ELISA studies were conducted to investigate the urokinase
      concentrations in urine obtained from males (22-60 years) with and without renal
      stones. These results showed a significant decrease in urinary urokinase
      concentration of renal stone patients which, once again, underlines the possible
      involvement of urokinase in renal stone formation. Therefore, it seems logical to
      conclude that urokinase may play an integral role in this multifactorial disease.

PMID- 9247910
TI  - Sudden infant death syndrome: a hypothesis.
AB  - A study of the strikingly low incidence of sudden infant death syndrome in
      Eastern countries revealed significant differences in infant handling thought to
      have an etiological bearing; therefore this writer suggested that adoption of
      certain Eastern methods of nursing may reduce the incidence of sudden infant
      death syndrome. A dramatic fall in incidence has resulted from implementing one
      of the suggestions made by the writer in 1983, namely the abandonment of the
      prone position, after initial opposition. The present hypothesis sets out to give
      a scientific explanation for this fall, and is a unified hypothesis explaining
      certain puzzling and disparate features of sudden infant death syndrome such as
      the remarkable winter incidence, age incidence, and the occurrence of sudden
      infant death syndrome during sleep, and is based on a postulated disturbance in
      thermoregulatory function (a unique hypothermia). Recommendations are made for
      evolving a test for sudden infant death syndrome-proneness and a possible method
      of treatment of a fatality within a short time frame.

PMID- 9247912
TI  - A hypothesis to explain the role of the suppressor and helper T cells in the
      immunologic selection of highly related human immunodeficiency virus isolates
      found in infected patients.
AB  - It is proposed that specific human immunodeficiency virus determinants in
      seropositive individuals are capable of evoking very strong suppressor T cell
      responses which inactivate certain helper T cells. This helper T cell suppression
      may be sufficient to inhibit the cytotoxic T cell recognition of these specific
      retroviral antigens and significantly reduce neutralizing antibody titers. As a
      consequence of the poor T helper cell responses to these different antigens, a
      number of related human immunodeficiency virus isolates are able to escape immune
      surveillance over the entire course of the infection. The selection and
      persistence of these distinct but related viral isolates may allow the human
      immunodeficiency virus infection to progress to other tissues and contribute to
      the gradual destruction of the remaining helper T cell population. Thus, the
      development of an effective antiviral therapy and possibly even a cure for the
      acquired immune deficiency syndrome may depend on the management of the
      suppressor and helper T cell activity in the infected individual.

PMID- 9247911
TI  - Estrogen receptor status of breast cancer: a marker of different stages of tumor
      or different entities of the disease?
AB  - Breast cancer can be divided into two types according to the estrogen receptor
      (ER) level of the tumor: ER-positive and ER-negative. Two hypotheses have been
      raised about the relationship between ER-positive and ER-negative breast tumors.
      One hypothesis considers ER status as an indicator of a different stage of the
      disease. The other regards ER-positive and ER-negative tumors as different
      entities. For both etiological and biological studies of breast cancer it is
      important to know which hypothesis is correct. In this paper, we review evidence
      for and against each hypothesis and suggest issues to be addressed in future
      studies.

PMID- 9247914
TI  - Relationship of dehydroepiandrosterone and cortisol in disease.
AB  - Does dehydroepiandrosterone act as an adrenal hormone in humans to maintain
      cortisol homeostasis by serving as a cortisol antagonist? If so,
      dehydroepiandrosterone might block the development of the diverse pathological
      processes potentiated by prolonged cortisol hyperactivity. And the plasma
      concentrations of total dehydroepiandrosterone and total cortisol, expressed as a
      C/D ratio, would have an important influence on the development of age-related
      pathology in diseases exacerbated by cortisol hyperactivity. Several major age
      related diseases, designated as cortisol-potentiated diseases, belong in this
      category. The C/D concept predicts, other factors being equal, that the risk of
      initiation and progression of these diseases at all ages is directly related to
      the C/D ratio, individuals with elevated C/D ratios being at high risk.

PMID- 9247913
TI  - Novel proprioceptive action in stepping down.
AB  - A hypothesis is offered which extends the concept of proprioception to use
      information necessarily obtained during the first part of a complex motion
      (stepping down) to facilitate the second part. It is suggested that, when the
      leading foot of a normal person stepping down arrives at its destination,
      relevant proprioceptive information is used by the following foot in its descent,
      to render its movement more efficient. Analogy to another effort-minimizing
      proprioceptive mechanism and a possible mechanical manifestation of the
      hypothesis are given.

PMID- 9247915
TI  - General anesthesia, respiratory and cardiac standstill triggered by the extra
      integumentary mechanical stimulation of foreign bodies in the airways.

PMID- 9247916
TI  - Blushing and social phobia: a neuroethological speculation.
AB  - Blushing is a well-known but relatively poorly understood phenomenon. This paper
      reviews the phenomenology, neurobiology, and psychology of blushing. We argue
      that a neuroethological understanding of blushing provides a useful explanation
      of many aspects of normal blushing, and leads to a useful account of social
      phobia. More specifically, we argue that social phobia can be conceptualized in
      terms of an inappropriate appeasement display.

PMID- 9247917
TI  - Were you knocked out? A team physician's approach to initial concussion
      management.
AB  - To present an evidence-based approach reviewing the acute management of
      concussive brain injury in sport. All published articles on the acute management
      of sport-related brain injury were extracted using searches of computerised
      databases (Medline, Embase, Sport Discus) as well as detailed literature reviews
      based upon the published bibliographies in this area. The review details the
      aspects where prospective scientific data is available upon which to base
      clinical management strategies. The first few minutes after an athlete receives a
      concussive injury provides a window of opportunity during which time the initial
      medical management forms a crucial and potentially lifesaving treatment. All
      clinicians involved in care of the concussed athlete need to have an
      understanding of the early management of the concussed athlete and a strategy by
      which they may manage such problems. An efficient and appropriate response to the
      immediate concussion management will help minimise the potential sequelae which
      may impact upon the athletes ability to return to sport.

PMID- 9247919
TI  - The disc at risk in athletes: perspectives on operative and nonoperative care.
AB  - Low back pain is the most common cause of disability in individuals below the age
      of 45 and the third most common cause of disability overall. Although acute back
      pain is generally felt to have a high probability of spontaneous resolution, the
      high recurrence rate of low back pain challenges the notion that resolution of
      symptoms is accompanied by restitution of function. Athletes who have lumbar
      spine dysfunction represent a particular challenge to the treating physician due
      to their high levels of activity and expectation of return to sport. Injuries to
      the intervertebral disc in the lumbar spine are a particular subset of spine
      injury. Management of intervertebral disc injuries, which is the focus of this
      section, is fraught with controversy. Although the majority of intervertebral
      disc injuries can be treated conservatively, the decision to follow an aggressive
      conservative versus surgical course in any given athlete must be made on an
      individual case basis.

PMID- 9247918
TI  - Alternative approaches to the assessment of mild head injury in athletes.
AB  - OBJECTIVES: Athletic trainers and team physicians are often faced with decisions
      concerning the severity and timing of an athletes return to play following mild
      head injury (MHI). These decisions can be the most difficult ones facing
      clinicians because of the limited amount of quantitative information indicating
      injury severity. Several authors have published guidelines for return to play
      following MHI, however these guidelines are based on limited scientific data. The
      purpose of this paper was to examine the effects of MHI on two objective
      measures, postural stability and cognitive function, to determine their
      usefulness in MHI assessment. The data gathered from these two measures has the
      potential to establish recovery curves based on objective data. METHODS: Eleven
      Division I collegiate athletes who sustained a MHI and eleven matched control
      subjects were assessed for postural stability and cognitive function at four
      intervals following injury. Postural stability was assessed using the Sensory
      Organization Test on the NeuroCom Smart Balance Master. Cognitive functioning was
      measured through the use of four neuropsychological tests: Stroop Test, Trail
      Making Test, Digits Span and Hopkins Verbal Learning Test. Separate mixed model
      repeated measures ANOVAs were calculated for the composite score and three ratio
      (vestibular, visual and somato-sensory) scores from the Sensory Organization Test
      and the scores from the neuropsychological test to reveal significant differences
      between groups and across days postinjury. RESULTS: A significant group by day
      interaction for overall postural stability (composite score) revealed that MHI
      athletes displayed increased postural instability for the first few days
      following MHI (p < .05). Analysis of the ratio scores revealed a significant
      interaction for the visual ratio. No significant group differences were revealed
      for any of the neuropsychological tests (p > .05), however significant day
      differences were revealed (p < .05). CONCLUSIONS: The results from this study
      indicate that athletes demonstrate decreased stability until 3 days postinjury.
      It appears this deficit is related to a sensory interaction problem, whereby the
      injured athlete fails to use their visual system effectively. These findings
      suggest that measures of postural stability may provide clinicians with a useful
      clinical tool for determining when an athlete may safely return to competition,
      although these findings need to be confirmed in larger groups of athletes.

PMID- 9247920
TI  - Stingers, transient quadriplegia, and cervical spinal stenosis: return to play
      criteria.
AB  - This article focuses on sports related spinal cord and nerve injuries, ranging
      from mild "stinger" syndrome to complete quadriplegia. Particular emphasis is
      placed on recommendations for return to competition after such injuries. Cervical
      spinal cord symptoms after a spine injury from contact sports require a more
      precise work up to detect cervical spinal stenosis than radiographic bone
      measurements alone can provide. Imaging technology such as MRI, contrast positive
      CT, and myelography more accurately identify true spinal stenosis and allow for
      safer return to play decisions.

PMID- 9247921
TI  - The diagnosis and treatment of cervical radiculopathy.
AB  - To provide a comprehensive review of the presentation, evaluation, differential
      diagnosis, treatment and return-to-play criteria which can be useful to the
      clinician caring for athletes with cervical radiculopathy. A review of the
      literature on cervical radiculopathy and sports injuries of the cervical spine
      was performed. This information was used in conjunction with the author's
      clinical experience to present a literature based approach to the diagnosis and
      treatment of cervical radiculopathy in athletic individuals. There was limited
      scientific literature on the evaluation and treatment of cervical radiculopathy
      in athletes. Many studies reported on the evaluation and treatment of the
      "burner" or "stinger" in the younger athlete which may represent a cervical
      radiculopathy in many of these cases. A nonoperative treatment plan using a
      logical step-wise approach is successful in the vast majority of these patients.
      Using the history and a detailed physical examination, along with imaging and
      other diagnostic studies when necessary, a proper diagnosis of cervical
      radiculopathy can be made. Once a discrete diagnosis is made, then a systematic
      approach to the treatment and rehabilitation can be implemented to optimize a
      safe return to competition.

PMID- 9247922
TI  - The biomechanics of cervical spine injury and implications for injury prevention.
AB  - Most catastrophic cervical spinal injuries occur as a result of head impacts in
      which the head stops and the neck is forced to stop the moving torso. In these
      situations the neck is sufficiently fragile that injuries have been reported at
      velocities as low as 3.1 m/s with only a fraction of the mass of the torso
      loading the cervical spine. Cervical spinal injury occurs in less than 20 ms
      following head impact, explaining the absence of a relationship between
      clinically reported head motions and the cervical spinal injury mechanism. In
      contrast, the forces acting on the spine at the time of injury are able to
      explain the injury mechanism and form a rational basis for classification of
      vertebral fractures and dislocations. Fortunately, most head impacts do not
      result in cervical spine injuries. Analysis of the biomechanical and clinical
      literature shows that the flexibility of the cervical spine frequently allows the
      head and neck to flex or extend out of the path of the torso and escape injury.
      Accordingly, constraints which restrict the motion of the neck can increase the
      risk for cervical spine injury. These observations serve as a foundation on which
      injury prevention strategies, including coaching, helmets, and padding, may be
      evaluated.

PMID- 9247923
TI  - Suggested management guidelines for participation in collision activities with
      congenital, developmental, or postinjury lesions involving the cervical spine.
AB  - Many conditions involving the cervical spine in the athlete require a management
      decision. The purpose of this paper is to present appropriate guidelines for
      return to collision activities in those with congenital, developmental, or post
      injury lesions. Information compiled from over 1200 cervical spine lesions
      documented by the National Football Head & Neck Injury Registry, an extensive
      literature review, as well as an understanding of injury mechanisms have resulted
      in reasonable management guidelines. Each of the congenital, developmental, and
      post-traumatic conditions presented are determined to present either no
      contraindication, relative contraindication, or an absolute contraindication on
      the basis of a variety of parameters. Conditions included in the discussion are:
      odontoid anomalies; spina bifida occulta; atlanto-occipital fusion; Klipple-Feil
      anomalies; cervical canal stenosis; spear tackler's spine; and traumatic
      conditions of the upper, middle, and lower cervical spine, including ligamentous
      injuries and fractures, intervertebral disc injuries, and post-cervical spine
      fusion. Emphasized is the fact that the proposed guidelines should be used in the
      decision-making process in conjuction with other factors such as the age,
      experience, ability of the individual, level of participation, position played,
      as well as the attitude and desires of the athlete and his parents after an
      informed discussion of the problem with particular regard to potential risk.

PMID- 9247924
TI  - Generation of hemoglobin peptides in the acidic digestive vacuole of Plasmodium
      falciparum implicates peptide transport in amino acid production.
AB  - Intraerythrocytic malaria parasites avidly consume hemoglobin as a source of
      amino acids for incorporation into parasite proteins. An acidic organelle, the
      digestive vacuole, is the site of hemoglobin proteolysis. Early events in
      hemoglobin catabolism have been well studied. Two aspartic proteases, plasmepsins
      I and II, and a cysteine protease, falcipain, cleave hemoglobin into peptides.
      While it has been presumed that hemoglobin peptide fragments are degraded to
      individual amino acids by exopeptidase activity in the digestive vacuole, this
      hypothesis lacks experimental support. Incubation of human hemoglobin with P.
      falciparum digestive vacuole lysate generated a series of discrete peptide
      fragments with cleavage sites an average of 8.4 amino acids apart. No free amino
      acids could be detected and there was no evidence of peptide heterogeneity due to
      exopeptidase trimming. These sites correspond to points of cleavage previously
      established for plasmepsin I, plasmepsin II, and falcipain as well as some novel
      sites that suggest the existence of an additional endoproteinase. By colorimetric
      assay, P. falciparum has abundant aminopeptidase activity but this activity is
      not found in the digestive vacuoles and the parasite lacks detectable
      carboxypeptidase activity altogether. These data support a model for hemoglobin
      catabolism wherein small peptides are formed from cleavage of hemoglobin by the
      enzymes of the digestive vacuole and then are transported through the membrane of
      the digestive vacuole to the cytoplasm. There, exopeptidase activity converts the
      peptides to individual amino acids for parasite growth and maturation.

PMID- 9247925
TI  - Expression, purification, and characterization of uracil
      phosphoribosyltransferase from Toxoplasma gondii.
AB  - The coding region derived from a full-length CDNA spanning the uracil
      phosphoribosyltransferase (UPRT) gene of Toxoplasma gondii has been ligated into
      a bacterial expression vector and overexpressed in E. coli. Recombinant UPRT
      protein migrated with a molecular mass of 27 kDa on SDS polyacrylamide gels and
      was purified to homogeneity by conventional protein purification techniques. In
      solution, UPRT behaved as a monomer and exhibited K(m)app values of 3.5 microM
      for uracil and 243 microM for phosphoribosylpyrophosphate, respectively. Other
      naturally occurring pyrimidine or purine bases were not recognized as substrates.
      [14C]Uracil phosphoribosylation was inhibited by 5-fluorouracil with a Ki value
      of 25 microM and was not activated by GTP. Ample quantities of recombinant enzyme
      are now available for biochemical and structural studies, facilitating evaluation
      of UPRT as a possible therapeutic target.

PMID- 9247927
TI  - Evidence for loss of mitochondria in Microsporidia from a mitochondrial-type
      HSP70 in Nosema locustae.
AB  - In molecular phylogenies based on ribosomal RNA, three amitochondriate protist
      lineages, Microsporidia, Metamonada (including diplomonads) and Parabasala
      (including trichomonads), are the earliest offshoots of the eukaryotic tree. As
      an explantation for the lack of mitochondria in these organisms, the hypothesis
      that they have diverged before the mitochondrial endosymbiosis is preferred to
      the less parsimonious hypothesis of several independent losses of the organelle.
      Nevertheless, if they had descended from mitochondrion-containing ancestors, it
      may be possible to find in their nuclear DNA genes that derive from the
      endosymbiont which gave rise to mitochondria. Based on similar evidence,
      secondary losses of mitochondria have recently been suggested for Entamoeba
      histolytica and for Trichomonas vaginalis. In this study, we have isolated a gene
      encoding a chaperone protein (HSP70, 70 kDa heat shock protein) from the
      microspordian Nosema locustae. In phylogenetic trees, this HSP70 was located
      within a group of sequences that in other lineages is targetted to the
      mitochondrial compartment, itself included in the proteobacterial clade. In
      addition, the N. locustae protein contained the GDAW(V) motif shared by
      mitochondrial and proteobacterial sequences, with only one conservative
      substitution. Moreover, microsporidia, a phylum which was assumed to emerge close
      to the base of the eukaryotic tree, appears as the sister-group of fungi in the
      HSP70 phylogeny, in agreement with some ultrastructural characters and
      phylogenies based on alpha- and beta-tubulins. Loss of mitochondria, now
      demonstrated for several amitochondriate groups, indicates that the common
      ancestor of all the extant eukaryotic species could have been a mitochondriate
      eukaryote.

PMID- 9247926
TI  - Purification, cloning, and expression of two closely related Trypanosoma brucei
      nucleic acid binding proteins.
AB  - Nucleic acid binding proteins in the trypanosomatid family are of particular
      interest because of several unusual molecular phenomena discovered in these
      organisms. We have purified two closely related proteins, p34 and p37, from the
      procyclic from of T. brucei using high salt extraction and single-stranded-DNA
      (ssDNA) agarose chromatography. Antibodies raised against the p34 protein showed
      crossreactivity with p37, suggesting relatedness. High performance liquid
      chromatography analysis and microsequencing of tryptic peptides derived from p34
      and p37 showed that the primary structures of the two proteins are nearly
      identical. We have cloned and sequenced the two genes encoding these two
      proteins. Protein sequences predicted from the cDNAs confirm the relatedness of
      the two proteins but also indicate the presence of an 18 amino acid insertion
      unique to one of the two proteins as well as several minor differences resulting
      from single amino acid changes. Three sequence motifs have been identified in
      both proteins: an N-terminal alanine, proline, and lysine rich domain, one and a
      half internal RNA-binding domains, and a C-terminal KKDX repeat region. Both
      proteins preferentially bind to heterogenous RNA and ssDNA versus double-stranded
      DNA and homopolymers. Both recombinant proteins have been expressed in E. coli
      and show properties indistinguishable from those observed with native p34/p37.

PMID- 9247928
TI  - Plasmodium falciparum asparagine and aspartate rich protein 2 is an evolutionary
      conserved protein whose repeats identify a new family of parasite antigens.
AB  - We describe here a new Plasmodium falciparum antigen, asparagine and aspartate
      rich protein 2 (PfAARP2) of 150 kDa, which is encoded by a unique gene on
      chromosome 1. PfAARP2 is first expressed 12 h post-invasion and accumulates in
      trophozoites and schizonts. Immunofluorescence studies indicate that PfAARP2 is
      translocated into the red blood cell cytoplasm. The central region of Pfaarp2
      contains blocks of repetitions encoding asparagine and aspartate residues, which
      define a new family of related genes dispersed on different chromosomes, and two
      members of this family have also been identified. Interestingly, the non-repeated
      N- and C-termini of PfAARP2 display significant similarity to two yeast and human
      predicted proteins, and its possible function is discussed.

PMID- 9247929
TI  - Cloning and expression of a cDNA encoding a nonintegrin laminin-binding protein
      from Echinococcus granulosus with localization of the laminin-binding domain.
AB  - We have isolated a cDNA from the hydatid tapeworm, Echinococcus granulosus,
      encoding a protein that binds laminin. This is the first report of a helminth
      parasite laminin-binding protein and the first description of a cDNA encoding a
      laminin-binding protein from a parasite. The cDNA clone (egmo3) was isolated from
      an E. granulosus protoscolex cDNA expression library, and identified on the basis
      of sequence homology to the nonintegrin mammalian metastasis-associated 67-kDa
      laminin receptor (67-LR). The amino acid sequence predicted from the cDNA
      sequence is 268 residues long with a calculated molecular mass of 29.9 kDa.
      Southern blot analysis suggested that many copies of the gene may occur in the E.
      granulosus genome. A Northern blot revealed that the gene is expressed as a
      single transcript of approximately 1 kb consistent with the size of the cDNA
      insert. Antibodies raised to the purified protein interacted with a 30 kDa
      protein in whole E. granulosus protoscoleces. A Western blot of the purified and
      refolded recombinant protein specifically bound 125I-labelled laminin, as did a
      synthetic peptide derived from the inferred amino acid sequence of egmo3 which is
      similar in homology to peptide G, the active ligand-binding site of 67-LR. We
      also isolated the 3' end of the cDNA encoding the homologous protein from the
      closely related species, E. multilocularis. The polypeptide encoded by egmo3 also
      shares substantial identity with the acidic class of ribosomal proteins which are
      involved in protein synthesis. As such, the egmo3 protein may be multifunctional
      in E. granulosus, acting as a laminin-binding molecule but also playing a role in
      cell division and growth.

PMID- 9247930
TI  - Cloning and characterization of a gene encoding a novel immunodominant antigen of
      Trypanosoma cruzi.
AB  - A Trypanosoma cruzi genomic expression library was screened with a pool of sera
      obtained from chronic chagasic patients. The recombinant antigen (Tc40) isolated
      from this library reacted with a large number of serum samples of chronic
      chagasic patients, suggesting that the presence of anti-Tc40 antibodies may be
      specifically associated to Chagas' disease. The full-length sequence of the Tc40
      gene was determined after isolation of genomic and cDNA clones. The Tc40 cDNA
      includes a large open reading frame (2745 bp-long) that encodes a polypeptide of
      100 kDa without any homology with previously described T. cruzi sequences. In
      contrast with other T. cruzi antigens whose immunodominant B-cell epitopes are
      composed by amino acid repetitive motifs, Tc40 does not show any amino acid
      repetition. Antibodies against the Tc40 recombinant protein reacted with three
      native polypeptides of 100, 41 and 38 kDa which are tightly associated with
      membranes or cytoskeleton and expressed in all developmental stages of the
      parasite life cycle. A transcript of 3.9-kb was detected in Northern blot
      analysis which is large enough to encode a 100 kDa polypeptide. Tc40 genes were
      mapped on a chromosomal band of 1.1 Mbp and in a few copies per haploid genome in
      the G strain.

PMID- 9247931
TI  - Protein phosphorylation during sexual differentiation in the malaria parasite
      Plasmodium falciparum.

PMID- 9247932
TI  - Molecular cloning and characterization of a second calcium-dependent protein
      kinase of Plasmodium falciparum.

PMID- 9247933
TI  - Identification and characterization of an ADP-ribosylation factor in Plasmodium
      falciparum.

PMID- 9247934
TI  - Expression of green fluorescent protein in Plasmodium falciparum.

PMID- 9247935
TI  - Limited sequence polymorphism in the Plasmodium falciparum merozoite surface
      protein 3.

PMID- 9247937
TI  - A dense granule protein (NCDG1) gene from Neospora caninum.

PMID- 9247936
TI  - Genomic representation of var gene sequences in Plasmodium falciparum field
      isolates from different geographic regions.

PMID- 9247938
TI  - We must prove our operations work.

PMID- 9247939
TI  - Physical therapy for TMD.

PMID- 9247940
TI  - Ketoconazole resistant oral candidiasis in HIV-infected patients.

PMID- 9247941
TI  - Multidrug intravenous sedation: determinants of the sedative dose of midazolam.
AB  - OBJECTIVES: The efficacy of multidrug intravenous sedation regimens in oral
      surgery is based on the ability to titrate opioids, benzodiazepines, and
      barbiturates to a desired level of relaxation. Dosage requirements to reach the
      initial sedation end points of slurred speech and ptosis of eyelids vary widely
      from one patient to another. STUDY DESIGN: An assessment of physical,
      cardiovascular, behavioral, and pharmacologic factors that might predict
      midazolam dosage requirements for the initial sedation titration was carried out
      with data collected from a large controlled clinical trial of fentanyl,
      midazolam, and methohexital sedation for third molar surgery. RESULTS: Dosage
      requirements for the initial titration of midazolam were found to be
      significantly higher when fentanyl was not included in the sedation regimen and
      when presedation heart rate and presedation systolic blood pressure were
      elevated.

PMID- 9247942
TI  - Effects of midazolam on pain sensations in the face.
AB  - OBJECTIVES: This study investigated the effects of midazolam, a sedative, on
      tactile and pain sensations on the skin of the chin. STUDY DESIGN: Thirty-seven
      volunteers were segregated into four groups; the first group was the control
      group; the second to fourth groups were administered 0.025 mg/kg, 0.05 mg/kg, and
      0.075 mg/kg of midazolam, respectively, as a bolus injection. All volunteers
      reclined in a dental chair for the experiment. Tactile and pain sensations were
      determined over time after injection of midazolam, the former using von Fray
      thread, the latter using an esthesiometer. RESULTS: Thresholds of tactile
      sensitivity and of pain were statistically significantly different from control
      values at 10 minutes after injection of midazolam in the 0.05 mg/kg group and in
      the 0.075 mg/kg group. CONCLUSION: Although 0.025 mg/kg of midazolam produced
      sedation, at least 0.05 mg/kg of this agent was required to alter the thresholds
      for perception of tactile and painful stimulation.

PMID- 9247943
TI  - Conservative management of osteoradionecrosis.
AB  - A retrospective records analysis of 32 patients with mandibular
      osteoradionecrosis seen between August 1960 and September 1995 was undertaken to
      determine the effectiveness of nonsurgical/nonhyperbaric oxygen conservative
      management. Two patients died before final analysis. Of those alive, 65.5% of
      patients were spared resection, having lesions resolve (48.3%), improve (3.4%),
      or asymptomatically stabilize (13.8%). Sequestrum production allowing "gentle"
      removal predicted a more favorable clinical course when managed conservatively
      compared with nonsequestrating lesions (p < 0.05). Criteria to define clinical
      osteoradionecrosis are proposed.

PMID- 9247944
TI  - The influence of laser parameter configurations at 9.3 microns on incisional and
      collateral effects in soft tissue.
AB  - These investigations were performed to determine histologic and incisional
      consequences of varying pulse duration, duty cycle, and average powers during
      laser incision at 9.3 microns in soft tissue. In 19 fresh pigs' jaws six
      standardized incisions 3 cm long were made per parameter with a template and
      motorized jig. Laser parameters investigated were average power: 1 to 9 W, duty
      cycle: 10% to 80%, and pulse duration: 1 to 200 msec. The gated Cw mode was used.
      Incision width and depth and collateral tissue effects were assessed
      statistically with general linear procedures. Multiple factors were found to
      influence the outcome of laser irradiation. Depth of incision correlated
      positively with average power. Tissue damage correlated strongly and negatively
      with all three variables. These results demonstrate that a wide range of surgical
      and collateral effects can be achieved with one specific laser device depending
      on the parameter configuration selected.

PMID- 9247945
TI  - Sarcoid-like foreign body reaction in body piercing: a report of two cases.
AB  - We report two cases of body piercing as a religious practice that subsequently
      led to the development of granulomatous nodules at previously punctured sites of
      the skin and oral mucosa. These lesions were diagnosed as sarcoid-like foreign
      body reaction after other possible causes including sarcoidosis, tuberculosis,
      tuberculoid leprosy, fungal infections, viral infections, and Crohn's disease
      were excluded.

PMID- 9247946
TI  - Trichinosis associated with carcinoma of the tongue: case report.
AB  - A rare presentation of Trichinella spiralis with squamous cell carcinoma of the
      tongue is reported. The possible carcinogenic potential of trichinosis and its
      management are discussed.

PMID- 9247947
TI  - Craniofacial and oral manifestations of trichorhinophalangeal syndrome type I
      (Giedion's syndrome): a case report.
AB  - A case of trichorhinophalangeal syndrome type I (Giedion's syndrome) is presented
      and discussed. Pathologic alterations, including oral and facial manifestations,
      and the clinical history of this unusual condition are described. The case is
      compared with others reported in the literature.

PMID- 9247949
TI  - Leiomyoma of the mandible: a rapid growing case with immunohistochemical and
      electron microscopic observations.
AB  - A rare case of leiomyoma of the mandible is reported together with the
      conventional histologic, immunohistochemical, and electron microscopic findings.
      On immunohistochemical evaluation the tumor cells were positive for vimentin,
      desmin, and alpha-smooth muscle actin but negative for neurogenic antigens and
      markers for vascular endothelial cells. Ultrastructural examination revealed
      smooth muscle cell differentiation. The Ki-67 labeling index was 4.7%. The tumor
      showed rapid increase in size and clinical features suggestive of malignancy.
      However, on histopathologic evaluation it was diagnosed as a benign neoplasm, and
      this diagnosis was supported by the results for mitotic rate, Ki-67 labeling
      index, and p53 immunostaining.

PMID- 9247948
TI  - Pigmented peripheral nerve sheath tumor of the oral cavity with expression of AP
      2 beta and c-RET: a case report.
AB  - Pigmented peripheral nerve sheath tumor of the oral cavity is a rare lesion and
      may be difficult to distinguish clinically from true melanocytic tumors. We
      report a case of pigmented peripheral nerve sheath tumor with a high degree of
      melanocytic differentiation and describe its histologic and ultrastructural
      features. Immunohistochemistry and polymerase chain reaction findings support the
      neural crest origin of the tumor. The clinical course of our case indicates that
      local recurrence may be a significant problem in pigmented peripheral nerve
      sheath tumor.

PMID- 9247950
TI  - Solitary angiokeratoma of the oral cavity.
AB  - Angiokeratoma is a rare, cutaneous disorder that typically occurs at multiple
      sites and is often associated with a number of metabolic disorders. Although
      solitary cutaneous forms have been reported, to date localized lesions within the
      oral cavity have not been described. We report on an 82-year-old man with a
      history of squamous cell carcinoma of the ear and scalp who also had a solitary
      pigmented lesion of the oral cavity. Excisional biopsy of the buccal mucosal
      lesion showed features consistent with angiokeratoma. We report the first intra
      oral solitary angiokeratoma and review the clinical and pathologic features of
      this unusual condition.

PMID- 9247951
TI  - Glandular odontogenic cyst: report of a case and review of the literature.
AB  - The glandular odontogenic cyst is a rare jawbone cyst of odontogenic origin,
      first described in 1988 by Gardner et al. We describe a previously unreported
      case of a combined cyst composed of glandular odontogenic cyst and ghost cell
      keratinization that was present for 33 years. We also reviewed the published 38
      cases of glandular odontogenic cyst found in the world literature and add this
      additional case.

PMID- 9247952
TI  - Trichilemmal cyst of the upper lip.
AB  - We report the apparent first case of a trichilemmal cyst presenting intraorally.
      Trichilemmal cysts are cysts of epithelial origin with a distinctive
      keratinization pattern that simulates that of the human anagen hair follicle
      between bulge and sebaceous gland and in the sac surrounding catagen hairs. This
      type of keratinization of outer root sheath epithelium occurs when it is freed
      from its internal cover of inner root sheath. This particular case showed
      evidence of mild epithelial proliferation and slight foci of "metaplastic"
      epidermoid keratinization, possibly related to mild trauma. The rarity of
      intraoral hairs undoubtedly accounts for the lack of reported cases of
      trichilemmal cysts in oral or perioral locations.

PMID- 9247953
TI  - Oral mucositis with features of psoriasis: report of a case and review of the
      literature.
AB  - An unusual case of oral mucositis with features of psoriasis is reported along
      with a review of the cases of oral psoriasis in the literature. The case reported
      involved a crusted lesion on the upper lip and erythematous lesions on the labial
      mucosa, buccal mucosa, and denture-bearing palatal mucosa. In addition, lesions
      resembling geographic tongue and ectopic geographic tongue were present. All
      lesions exhibited multiple small pustules. The review of the literature compares
      the distribution and clinical appearance of previously reported cases of oral
      psoriasis.

PMID- 9247954
TI  - Growth patterns of Candida albicans in relation to radicular dentin.
AB  - Candida albicans is the most common fungal pathogen isolated from the oral
      cavity. The role of this organism as an endodontic pathogen is poorly understood.
      OBJECTIVES: The aim of this study was to observe the interaction of C. albicans
      with root canal walls and the growth patterns of this microorganism in relation
      to radicular dentin. STUDY DESIGN: Fifteen root sections were infected with C.
      albicans grown in calf serum and incubated for various periods. The sections were
      fixed in glutaraldehyde, split into two halves, and evaluated by scanning
      electron microscopy. RESULTS: Blastospores and hyphal structures were observed on
      the root canal walls of all specimens. Filamentous hyphal form was dominant in 5
      day specimens. Most of the hyphae and blastospores showed penetration into
      dentinal tubules. The body of germinating mother cells and hyphae demonstrated
      collapsed cell walls as a result of vacuole formation. CONCLUSIONS: With this
      invasive affinity to dentinal structures, C. albicans may be considered a
      dentinophilic microorganism.

PMID- 9247955
TI  - Demineralization of resected root-ends with methylene blue dye.
AB  - OBJECTIVES: This study evaluated the ability of methylene blue solutions of
      different concentration, pH, and time exposure to remove the smear layer from
      resected root-ends. STUDY DESIGN: Resected root-ends were treated with either 2%
      methylene blue dye for intervals of 5 to 11 minutes or 1% methylene blue for 7 to
      9 minutes and examined with a scanning electron microscope for smear layer
      removal. Two minute applications of saline solution and 50% citric acid served as
      controls. RESULTS: All methylene blue solutions were found to be ineffective in
      removing the smear layer at all time intervals tested. An experimental solution
      of 1% methylene blue in 50% citric acid was found to predictably remove the smear
      layer during a 2 minute application and retained all the favorable staining
      characteristics of the dye. Fifty percent citric acid solutions applied for 3
      minutes appeared to overdemineralize the root-end and gave poorer results than 2
      minute applications. CONCLUSIONS: Smear layer removal was pH dependent. Methylene
      blue solutions are clinically unsuitable for smear layer removal.

PMID- 9247956
TI  - Diagnosis of an advanced endodontic/periodontic lesion: report of a case.
AB  - Diagnosis of endodontic/periodontic lesions is often a challenge for clinicians.
      Treatment will not be successful without correct diagnosis. This article presents
      an advanced case of an endodontic/periodontic lesion in a patient who was
      referred to a periodontist. After careful examination of the patient, as well as
      consultation with an endodontist, an endodontic diagnosis was made and the
      patient treated accordingly. Success was attained without periodontal
      intervention.

PMID- 9247957
TI  - The influence of observer calibration in temporomandibular joint magnetic
      resonance imaging diagnosis.
AB  - OBJECTIVE: This study was undertaken to investigate the potential of reducing
      observer variation through a calibration program. STUDY DESIGN: The study was
      based on three sets of randomly selected temporomandibular joint magnetic
      resonance images. Each set consisted of bilateral images from 20 consecutive
      patients with temporomandibular disorders. As a baseline, three well-experienced
      noncalibrated investigators interpreted the images individually for disk position
      and disk configuration. After the initial interpretation, interobserver agreement
      was calculated as a kappa index and presented to the examiners. On the same
      occasion, the investigators analyzed agreement between them on the criteria to be
      used. RESULTS: Overall data in this study showed an increase in the frequency of
      interobserver agreement with regard to disk position after the calibration trials
      were instituted. With regard to disk configuration, substantial interindividual
      variations were observed even after the observers reached consensus as to the
      criteria to be used. CONCLUSIONS: These data suggest that after calibration
      trials, it is possible for three examiners to obtain reliable and reproducible
      results in reporting temporomandibular joint disk position on magnetic resonance
      images.

PMID- 9247958
TI  - Imaging findings of lipomas in the orofacial region with CT, US, and MRI.
AB  - OBJECTIVE: The aim of this study was to document retrospectively the imaging
      findings of lipomas with the use of computed tomography, ultrasonography, and
      magnetic resonance imaging. STUDY DESIGN: Thirteen patients with 11 lipomas and 2
      lipomatoses were evaluated. Eleven cases were examined by computed tomography, 9
      by ultrasonography, and 3 by magnetic resonance imaging. RESULTS: Lipomas had a
      density ranging from -134 to -83 Hounsfield units, (mean-108) on the computed
      tomography images. The margins were ill defined in 9 of 10 cases. The superficial
      muscles were displaced externally in 8 cases and internally in 2 cases. With
      ultrasonography, 8 lesions were hypoechoic, and one was hyperechoic. All three
      lesions had a high signal intensity on both T1- and T2-weighted images.
      CONCLUSIONS: Lipomas had a specific range of computed tomography Hounsfield unit
      values and also displaced the surrounding soft tissue. Although some variation in
      the ultrasonographic appearance was observed, the lesions tended to be
      hypoechoic. These findings may be useful for diagnosing lipomas in the orofacial
      region.

PMID- 9247959
TI  - The effect of image variations on fractal dimension calculations.
AB  - OBJECTIVES: We used digitized dental radiographs of alveolar bone to test the
      hypothesis that the fractal dimension, as calculated with the program
      "ImageFractal" was independent of variations in X-ray exposure, beam alignment,
      and region of interest placement. STUDY DESIGN: The radiographic data set
      consisted of 72 radiographs digitized with 200 microns pixels. Radiographs were
      obtained with the use of three time settings and two alignments. Rectangular
      regions of interest were placed on each digital image over the interdental bone
      between the mandibular first and second molars on six hemimandibles. Each of six
      hemimandibles had identical copies of a unique region of interest placed on every
      image in its series. New regions were made 3 months later. A fractal dimension
      was computed from each region of interest with the caliper method included in
      ImageFractal, a public domain program available through National Institutes of
      Health. The resulting fractal dimensions were evaluated with two repeated
      measures analysis of variance. RESULTS: No significant differences were found
      between the fractal dimensions calculated for baseline images and those from
      overexposed and underexposed images, from images with 4 to 6 degrees of alignment
      variations, or from repeat regions of interest. CONCLUSION: The results support
      the hypothesis that fractal dimensions derived from digitized dental radiographs
      are not affected by variations in exposure or small variations in alignment and
      imply an absolute region of interest placement may not be necessary. However,
      caution should be used with the use of the fractal dimension to discriminate
      among alveolar bone variations until further research is performed.

PMID- 9247960
TI  - Effect of the geometry of the intraoral position-indicating device on effective
      dose.
AB  - OBJECTIVE: The objective of this study was to calculate and compare the effective
      dose and to estimate risk from the use of intraoral position-indicating devices
      of differing geometries. STUDY DESIGN: Thermoluminescent dosimeters were placed
      at selected sites in the upper portion of a tissue-equivalent human phantom to
      record the equivalent dose to weighted tissues and organs. The phantom was
      exposed to simulated complete mouth surveys with either a long (29.8 cm) or short
      (19.6 cm) round open-end position-indicating device, a long (35.3 cm) or short
      (23.3 cm) rectangular open-end position-indicating device, or a pointed (29.6 cm)
      closed-end position-indicating device. RESULTS: The effective dose was calculated
      as the sum of the equivalent doses to each organ or tissue multiplied by that
      organ or tissue's weighting factor. The salivary glands were included as part of
      the remainder. The effective dose ranged from 362 micro Sv for the pointed
      position-indicating device, to 63 micro Sv for both the long and the short
      rectangular position-indicating devices. CONCLUSIONS: These effective doses were
      calculated to represent a probability for stochastic effects that range in
      magnitude from 26 x 10(-6) to 4.6 x 10(-6).

PMID- 9247961
TI  - Ganglionic axons in motor roots and pia mater.
AB  - In addition to motor axons and preganglionic axons, ventral roots contain
      unmyelinated or thin myelinated sensory axons and postganglionic sympathetic
      axons. It has been said that ventral roots channel sensory axons to the CNS.
      However, it now seems that these axons end blindly, shift to the pia or loop and
      return towards the periphery and that these units reach the CNS via dorsal roots.
      Sensory ventral root axons project from a variety of somatic or visceral
      receptors; some of them are third branches of dorsal root afferents and some seem
      to lack a CNS projection. Many ventral root afferents contain substance P (SP)
      and/or calcitonin gene-related peptide (CGRP). These fibres are not affected by
      neonatal capsaicin treatment and they cannot induce radicular or pial
      extravasation. Some thin ventral root axons are sympathetic and relate to blood
      vessels. Afferents containing SP and/or CGRP and sympathetic axons also occur in
      the spinal pia mater. The sensory axons mediate pain. They might also have
      vasomotor, tissue-regulatory and/or mechanoreceptive functions. The motor roots
      of cranial nerves IV, VI and XI contain unmyelinated axons arranged like in
      ventral roots outside the autonomic outflow. However, the motor root of cranial
      nerve V channels some unmyelinated axons into the CNS. The occurrence of thin
      axons in ventral roots and pia mater changes during development and ageing. After
      peripheral nerve injury, ipsilateral ventral roots and pia are invaded by new
      sensory and postganglionic sympathetic axons.

PMID- 9247962
TI  - Highest level automatisms in the nervous system: a theory of functional
      principles underlying the highest forms of brain function.
AB  - A concept that all hierarchical levels of the nervous system are built according
      to the same functional principles is proposed. Each level is responsible for a
      discrete type or set of automatisms, is a learning system, and contains two
      distinct functional subdivisions: (1) a controller, a subsystem providing a
      governing set of rules or commands-a control law-that directs the action of the
      recipient of these rules-the controlled object; and (2) a model, a subsystem that
      generates a model of object behavior, i.e. afferent information flow expected
      from the controlled object. A control system such as this receives two types of
      afferent signals-initiating and informational. The difference between these
      signals is that a control system minimizes initiating signals during the
      realization of an automatism, i.e. a control neural network utilizes
      informational signals to compute the proper output that minimizes the initiating
      input signal. A mismatch or error signal, a type of initiating signal, is
      responsible for learning. Both the control law and the model can be adjusted
      during learning. The learning process starts when the error signal increases and
      stops when it is minimized. A network hierarchy is structurally and functionally
      organized in such a way that a lower control system in the nervous system becomes
      the controlled object for a higher one. This hierarchy leads to a generalization
      of encoded functional parameters and, consequently, the working space for each
      higher level control system becomes more abstracted. This is the reason why each
      hierarchical level within the control nervous system uses detectors specific for
      feature of the controlled object and the environment that match the control needs
      in order to obtain information about the current state of the object in the
      environment. Movement of information toward higher hierarchical levels also is
      accompanied by an increase in the duration of initiating signals within each
      control system. The ability to store a long prehistory of preceding events is
      considered as the mechanism that necessitated the invention of more complex and
      more rapid forms of learning such as operant learning, and made possible more
      complex multistep computational algorithms that require memorization of the
      results of previous intermediate computations. The functions of the cerebellum,
      the limbic system and the cortico-basal ganglia-thalamocortical loops are
      analyzed to illustrate the utility and applicability of this theoretical concept.
      Basal ganglia-thalamocortical loops are described as modeling, predictive loops,
      and their dopaminergic innervation as an error distribution system.

PMID- 9247963
TI  - Invariant face and object recognition in the visual system.
AB  - Neurophysiological evidence is described, showing that some neurons in the
      macaque temporal cortical visual areas have responses that are invariant with
      respect to the position, size and view of faces and objects, and that these
      neurons show rapid processing and rapid learning. A theory is then described of
      how such invariant representations may be produced in a hierarchically organized
      set of visual cortical areas with convergent connectivity. The theory proposes
      that neurons in these visual areas use a modified Hebb synaptic modification rule
      with a short-term memory trace to capture whatever can be captured at each stage
      that is invariant about objects as the object changes in retinal position, size,
      rotation and view. Simulations are then described which explore the operation of
      the architecture. The simulations show that such a processing system can build
      invariant representations of objects.

PMID- 9247964
TI  - Neuroimmunomodulation via limbic structures--the neuroanatomy of
      psychoimmunology.
AB  - During the last 20 years, mutual communications between the immune, the endocrine
      and the nervous systems have been defined on the basis of physiological,
      cellular, and molecular data. Nevertheless, a major problem in the new discipline
      "Psychoneuroimmunology" is that controversial data and differences in the
      interpretation of the results make it difficult to obtain a comprehensive
      overview of the implications of immunoneuroendocrine interactions in the
      maintenance of physiological homeostasis, as well as in the initiation and the
      course of pathological conditions within these systems. In this article, we will
      first discuss the afferent pathways by which immune cells may affect CNS
      functions and, conversely, how neural tissues can influence the peripheral immune
      response. We will then review recent data, which emphasize the
      (patho)physiological roles of hippocampal-amygdala structures and the nucleus
      accumbens in neuroimmunomodulation. Neuronal activity within the hippocampal
      formation, the amygdaloid body, and the ventral parts of the basal ganglia has
      been examined most thoroughly in studies on neuroendocrine, autonomic and
      cognitive functions, or at the level of emotional and psychomotor behaviors. The
      interplay of these limbic structures with components of the immune system and
      vice versa, however, is still less defined. We will attempt to review and discuss
      this area of research taking into account recent evidences for neuroendocrine
      immunoregulation via limbic neuronal systems, as well as the influence of
      cytokines on synaptic transmission, neuronal growth and survival in these brain
      regions. Finally, the role of limbic structures in stress responses and
      conditioning of immune reactivity will be commented. Based on these data, we
      propose new directions of future research.

PMID- 9247965
TI  - Interrelationships between astrocyte function, oxidative stress and antioxidant
      status within the central nervous system.
AB  - Astrocytes have, until recently, been thought of as the passive supporting
      elements of the central nervous system. However, recent developments suggest that
      these cells actually play a crucial and vital role in the overall physiology of
      the brain. Astrocytes selectively express a host of cell membrane and nuclear
      receptors that are responsive to various neuroactive compounds. In addition, the
      cell membrane has a number of important transporters for these compounds. Direct
      evidence for the selective co-expression of neurotransmitters, transporters on
      both neurons and astrocytes, provides additional evidence for metabolic
      compartmentation within the central nervous system. Oxidative stress as defined
      by the excessive production of free radicals can alter dramatically the function
      of the cell. The free radical nitric oxide has attracted a considerable amount of
      attention recently, due to its role as a physiological second messenger but also
      because of its neurotoxic potential when produced in excess. We provide,
      therefore, an in-depth discussion on how this free radical and its metabolites
      affect the intra and intercellular physiology of the astrocyte(s) and surrounding
      neurons. Finally, we look at the ways in which astrocytes can counteract the
      production of free radicals in general by using their antioxidant pathways. The
      glutathione antioxidant system will be the focus of attention, since astrocytes
      have an enormous capacity for, and efficiency built into this particular system.

PMID- 9247966
TI  - Cell surface adenosine deaminase: much more than an ectoenzyme.
AB  - During the last 10 years, adenosine deaminase (ADA), an enzyme considered to be
      cytosolic, has been found on the cell surface of many cells, therefore it can be
      considered an ectoenzyme. EctoADA, which seems to be identical to intracellular
      ADA and has a globular structure, does not interact with membranes but with
      membrane proteins. Two of these cell surface receptors for ectoADA have been
      identified: CD26 and A1 adenosine receptors (A1R). Apart from degradation of
      extracellular adenosine another functional role of ectoADA has been assigned.
      EctoADA is able to transmit signals when interacting with either CD26 or A1R. In
      this way, it acts as a co-stimulatory molecule which facilitates a variety of
      specific signalling events in different cell types. The heterogeneous
      distribution of the enzyme in the nervous system indicates that ectoADA may be a
      neuroregulatory molecule. On the other hand, ectoADA might act as a bridge
      between two different cells thus raising the possibility that it may be important
      for the development of the nervous system.

PMID- 9247967
TI  - Tetrahydrobiopterin, nitric oxide and regulation of cerebral arterial tone.
AB  - Tetrahydrobiopterin is an essential cofactor required for activity of nitric
      oxide synthases. Existing evidence suggests that, during activation of
      constitutive and inducible isoforms of nitric oxide synthase, tetrahydrobiopterin
      is needed for allosteric and redox activation of enzymatic activity. However,
      precise mechanisms underlying the role of tetrahydrobiopterin in regulation of
      nitric oxide formation is not fully understood. In cerebral and peripheral
      arteries, increased availability of tetrahydrobiopterin can augment production of
      nitric oxide. In contrast, in arteries depleted of tetrahydrobiopterin,
      production of nitric oxide is impaired. Proinflammatory cytokines enhance mRNA
      expression of the rate-limiting enzyme of tetrahydrobiopterin biosynthesis, GTP
      cyclohydrolase I and stimulate production of tetrahydrobiopterin. The ability of
      vascular tissues to synthesize tetrahydrobiopterin plays an important role in
      regulation of nitric oxide synthase under physiological conditions as well as
      during inflammation and sepsis. More recent studies concerning expression and
      function of recombinant nitric oxide synthases suggest that availability of
      tetrahydrobiopterin is important for production of nitric oxide in genetically
      engineered blood vessels. In this review, mechanisms regulating availability of
      intracellular tetrahydrobiopterin and its role in control of vascular tone under
      physiological and pathological conditions will be discussed.

PMID- 9247968
TI  - Metaplasticity: a new vista across the field of synaptic plasticity.
AB  - Over the past 20 years there has been an increasing understanding of the
      properties and mechanisms underlying long-term potentiation (LTP) and long-term
      depression (LTD) of synaptic efficacy, putative learning and memory mechanisms in
      the mammalian brain. More recently, however, it has become apparent that synaptic
      activity can also elicit persistent neuronal responses not manifest as changes in
      synaptic strength. Some of these changes may nonetheless modify the ability of
      synapses to undergo strength changes in response to subsequent episodes of
      synaptic activity. This kind of activity-dependent modulatory plasticity we have
      termed "metaplasticity". Metaplasticity has been observed physiologically as an
      inhibition of LTP and concomitant facilitation of LTD by prior N-methyl-D
      aspartate receptor activation or, conversely, a facilitation of LTP induction by
      prior metabotropic glutamate receptor activation. The examples of metaplasticity
      described to date are input specific, and last as long as several hours. The
      mechanisms underlying such phenomena remain to be fully characterized, although
      some likely possibilities are an altered N-methyl-D-aspartate receptor function,
      altered calcium buffering, altered states of kinases or phosphatases, and a
      priming of protein synthesis machinery. While some details vary, experimentally
      observed metaplasticity bears some similarity to the "sliding threshold" feature
      of the Bienenstock, Cooper and Munro model of experience-dependent synaptic
      plasticity. Metaplasticity may serve several functions including (1) providing a
      way for synapses to integrate a response across temporally spaced episodes of
      synaptic activity and (2) keeping synapses within a dynamic functional range, and
      thus preventing them from entering states of saturated LTP or LTD.

PMID- 9247969
TI  - Free D-aspartate and D-serine in the mammalian brain and periphery.
AB  - It has long been assumed that L-forms of amino acids exclusively constitute free
      amino acid pools in mammals. However, a variety of studies in the last decade has
      demonstrated that free D-aspartate and D-serine occur in mammals and may have
      important physiological function in mammals. Free D-serine is confined
      predominantly to the forebrain structure, and the distribution and development of
      D-serine correspond well with those of the N-methyl-D-aspartate (NMDA)-type
      excitatory amino acid receptor. As D-serine acts as a potent and selective
      agonist for the strychnine-insensitive glycine site of the NMDA receptor, it is
      proposed that D-serine is a potential candidate for an NMDA receptor-related
      glycine site agonist in mammalian brain. In contrast, widespread and transient
      emergence of a high concentration of free D-aspartate is observed in the brain
      and periphery. Since the periods of maximal emergence of D-aspartate in the brain
      and periphery occur during critical periods of morphological and functional
      maturation of the organs, D-aspartate could participate in the regulation of
      these regulation of these developmental processes of the organs. This review
      deals with the recent advances in the studies of presence of free D-aspartate and
      D-serine and their metabolic systems in mammals. Since D-aspartate and D-serine
      have been shown to potentiate NMDA receptor-mediated transmission through the
      glutamate binding site and the strychnine-insensitive glycine binding site,
      respectively, and have been utilized extensively as potent and selective tools to
      study the excitatory amino acid system in the brain, we shall discuss also the
      NMDA receptor and uptake system of D-amino acids.

PMID- 9247970
TI  - Lack of any additional benefit in combining aspirin with iloprost in a canine
      model of myocardial reperfusion injury.
AB  - The effects of iloprost infusion (100 ng/kg/min for 75 min) alone and in
      combination with aspirin (3 mg/kg IV bolus) were compared in a canine model of
      myocardial reperfusion injury. Regional ischemia of 40 min was produced by
      temporary occlusion of the left anterior descending coronary artery, after which
      the myocardium was reperfused for a period of 3 hours. Mean arterial pressure
      (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive
      (+) LVdP/dtmax and negative (-) LVdP/dtmax were monitored. Rate pressure product
      and (-) dP/dt/Pmax were also derived from the above. Myocardial tissue levels of
      adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate were
      estimated. Following reperfusion in the saline treated group, there was a
      significant fall in (i) MAP, (ii) (+) LVdP/dtmax and (iii) (-) LVdP/dtmax. LVEDP
      was corrected about 2 hours after reperfusion. Despite correction of lactate
      accumulation, ATP and glycogen were not restored although the CP store was
      replenished. The hemodynamic profiles in both iloprost and in combination treated
      groups were similar; (i) depressed MAP (particularly during iloprost infusion)
      without any significant change in HR (ii) no significant depression in (+)
      LVdP/dtmax (iii) depression in (-) LVdP/dtmax but not when corrected for lower
      Pmax and (iv) a significant reduction in the incidence of reperfusion
      arrhythmias. Similarly, in both the drug/s treated groups, ATP, CP and lactate
      were normalised although glycogen store was not restored. The results of this
      study indicate (i) cardioprotective effect of iloprost even when administered
      prior to reperfusion and (ii) no additional protective effect of combining
      iloprost and aspirin.

PMID- 9247971
TI  - Antithrombotic effects of endocardial endothelial cells-comparison with coronary
      artery endothelial cells.
AB  - The purpose of this study was to assess the anti-platelet properties of
      endocardial endothelial cells (EECs) by measuring platelet aggregation after a
      brief incubation with cultured EECs. EECs were isolated from the right ventricles
      of porcine hearts and coronary artery endothelial cells (C-ECs) were also
      isolated from the same animals. After brief incubations (2-min) of platelet
      suspensions with cultured EEC and CEC monolayers, platelet aggregation in
      response to thrombin and 6-keto-PGF1 alpha (a stable metabolite of PGI2) content
      of platelet suspensions were measured. Platelet aggregation was significantly
      inhibited by a brief incubation of platelet suspensions with EEC and C-ECs
      monolayers. Pretreatment of EECs and C-ECs with indomethacin (5 x 10(-5) M)
      restored platelet activity, but pretreatment with N omega-nitro-L-arginine methyl
      ester (L-NAME, 5 x 10(-5) M) or hemoglobin (1 x 10(-6) M) did not. Platelet/EEC
      interactions multiplicatively increased the 6-keto-PGF1 alpha content of platelet
      suspensions and the 6-keto-PGF1 alpha content of platelet suspensions after
      incubations with EECs correlated significantly with the inhibition of platelet
      aggregation. Both the anti-aggregation properties and 6-keto-PGF1 alpha
      production were significantly greater in EECs than in C-ECs. A brief incubation
      (2-min) with PDGF (10 ng/ml) or TGF-beta (1 and 10 ng/ml) stimulated 6-keto-PGF1
      alpha production in EECs but not in C-ECs, although these growth factors
      stimulated 6-keto-PGF1 alpha production in C-ECs after a longer incubation time
      (30 or 60 min). In this study, after a brief incubation (2-min) with platelet
      suspensions, EECs inhibited platelet aggregation mainly through the release of
      PGI2 but not EDRF. As this anti-aggregation property was significantly greater in
      EECs than in C-ECs, it is suggested that endocardial endothelial PGI2 may inhibit
      both intracardiac and intracoronary artery thrombus formation, contributing to
      the prevention of myocardial ischemia.

PMID- 9247972
TI  - Influence of nitric oxide synthase and kinin antagonists on metabolic parameters
      in chronic streptozotocin-induced diabetes mellitus.
AB  - In vivo administration of HOE 140 (a new bradykinin receptor antagonist) and L
      NAME (nitric oxide synthase inhibitor) was performed in chronic streptozotocin
      diabetic rats. Basal increases (in umol.g dw-1) in liver (45.0 +/- 3.4.1) and
      uterine (40.0 +/- 2.95) triglyceride levels in diabetic animals vs control
      (liver: 34.0 +/- 3.87; uterus: 30.2 +/- 4.01) were partially prevented by L-NAME
      (p < 0.01), HOE 140 (p < 0.01) and L-NAME + HOE 140 (p < 0.01). High glycogen
      levels (in mg.g dw-1) observed in diabetic uterine tissue (3.07 +/- 0.90), and
      decreased glycogen content detected in diabetic liver (11.64 +/- 1.50) vs.
      control (uterus: 1.59 +/- 0.15, liver: 17.25 +/- 0.87) were unaffected. Uterine
      14CO2 production from 14C-U-Glucose (in uCi.mg dw), which is lower in diabetic
      (35.0 +/- 5.12) than in control (50.12 +/- 4.54) tissues, was improved by HOE 140
      (p < 0.05) and L-NAME+HOE 140 (p < 0.05), while hepatic glucose oxidation was not
      increased by the drugs. Glycemia levels were decreased in diabetic rats injected
      with L-NAME and L-NAME plus HOE 140. Pancreatic 6-Keto-prostaglandin F1 alpha to
      Thromboxane B2 ratio was lower in diabetic animals than in controls, and L-NAME
      and/or HOE 140 treatment prevented the decrement. These findings suggest that
      vasoactive compounds might prevent streptozotocin-induced damage in pancreatic
      tissue from chronic diabetic rats.

PMID- 9247973
TI  - PGE1 or PGE2 not LH regulates secretion of progesterone in vitro by the 88-90 day
      ovine corpus luteum of pregnancy.
AB  - Secretion of progesterone in vitro by mature day 8 ovine corpora lutea (CL) of
      the estrous cycle was increased linearly by ovine LH (1, 10 and 100 ng/ml) or
      prostaglandin E2 (PGE2) 1, 10 and 100 ng/ml) in a dose dependent manner (P < or =
      0.05). Progesterone secretion in vitro by 88-90 day ovine CL of pregnancy was not
      affected P > or = 0.05 by LH (1, 10 and 100 ng/ml) while prostaglandin E1 (PGE1)
      1, 10 and 100 ng/ml) increased (P < or = 0.05) secretion of progesterone in a
      dose dependent manner and PGE2 (1, 10 and 100 ng/ml) increased (P < or = 0.05)
      secretion of progesterone only at the 100 ng/ml dose. Day 8 ovine CL of the
      estrous cycle did not secrete (P > or = 0.05) detectable quantities of
      prostaglandin F2 alpha (PGF2 alpha) or prostaglandin E (PGE) while 88-90 day
      ovine CL of pregnancy secrete PGE (P < or = 0.05) but not PGF2 alpha (P > or =
      0.05). Regulation of PGE secretion by 88-90 day ovine CL of pregnancy may be via
      pregnancy specific protein B (PSPB), which increased (P < or = 0.05) PGE and
      progesterone but not PGF2 alpha (P > or = 0.05) secretion. Secretion of
      progesterone by CL of 88-90 days of pregnancy was not affected by IGF1, IGF2, PAF
      16, PAF-18, oxytocin, PGI2, PGD2 or leukotriene C4 (P > or = 0.05). It is
      concluded that PGE1 or PGE2 but not LH regulates secretion of progesterone in
      vitro by 88-90 day ovine CL of pregnancy. In addition, it is concluded that 88-90
      day ovine CL of pregnancy secretes it's own luteotropin, which is PGE. Secretion
      of PGE by ovine CL of pregnancy may be regulated by PSPB.

PMID- 9247974
TI  - Enhancement of prostaglandin E2 production by epidermal growth factor requires
      the coordinate activation of cytosolic phospholipase A2 and cyclooxygenase 2 in
      human squamous carcinoma A431 cells.
AB  - We demonstrated the effect of epidermal growth factor (EGF) on the production of
      PGE2 in human squamous carcinoma A431 cells. The production of PGE2 was increased
      by stimulating the cells with EGF for 2 h and reached a maximum for 10 h. EGF was
      also found to augment the release of arachidonic acid (AA) following the increase
      in phospholipase A2 (PLA2) activity (1.7-fold). The induced PLA2 activity was
      diminished by 4-bromophenacyl bromide, but not by dithiothreitol, indicating that
      the EGF-induced release of AA was due to the increase in the activity of
      cytosolic PLA2 (cPLA2). On the other hand, cyclooxygenase (COX) activity was
      increased (1.6-fold) within 2 h after the EGF-treatment and the induced activity
      was inhibited by cycloheximide. In addition, Northern blot analysis showed that
      the level of COX-2 mRNA was increased by the EGF-treatment, whereas no COX-2 mRNA
      was detected in the untreated cells, indicating that the EGF-induced COX activity
      was resulted from the increase in the production of COX-2. These results suggest
      that EGF augments the production of PGE2 by increasing not only the activity of
      cPLA2 but also the production of COX-2 in A431 cells.

PMID- 9247976
TI  - Schizophrenia and the ciliary neurotrophic factor (CNTF) gene: no evidence for
      association.
AB  - The ciliary neurotrophic factor (CNTF) gene is considered a candidate gene for
      schizophrenia, in view of the neurodevelopmental hypothesis of the disorder.
      Recently, controversial results regarding an association between psychiatric
      disorders; mainly schizophrenia, and a null mutation of the CNTF gene were
      reported. We investigated this mutation in 138 Japanese patients with
      schizophrenia and 140 healthy control subjects. No significant difference was
      observed in allele frequencies or genotype distribution between the patients and
      control subjects. Our results did not provide evidence for the involvement of the
      null mutation of the CNTF gene in the development of schizophrenia.

PMID- 9247975
TI  - Variants in neurotrophic factor genes and schizophrenic psychoses: no
      associations in a Spanish population.
AB  - Possible associations between schizophrenic psychoses, a ciliary neurotrophic
      factor (CNTF) null mutation and a neurotrophin in 3 (NT3) bi-allele polymorphism
      were investigated in a Spanish population. The sample consisted of 107 patients
      suffering from schizophrenic psychoses and 100 healthy volunteers. There was no
      statistical difference in the frequencies of the mutant CNTF allele in the index
      and control groups (0.125 vs. 0.121). The frequency of the rare NT3 allele (Glu)
      was very low and similar in both groups (0.005). Previous findings supporting the
      involvement of these genetic markers in the pathogenesis of schizophrenic
      psychoses were thus not confirmed. In light of neurodevelopmental hypotheses of
      schizophrenia, however, genes coding for neurotrophic factors remain interesting
      susceptibility loci in schizophrenia research. Subsequent studies should not
      focus exclusively on genetic alterations but also take into account secondary
      changes of the neurotrophic factor system at the mRNA and protein levels.
      Further, the current unsatisfying operationalized classification of the
      heterogeneous syndrome 'schizophrenia' remains a crucial problem that could be
      partially resolved by introducing more differentiated diagnoses defined on the
      basis of neurobiological criteria.

PMID- 9247977
TI  - Plasma levels of interleukin-6 and tumor necrosis factor alpha in chronic
      schizophrenia: effects of clozapine treatment.
AB  - Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha)
      were assessed in 17 chronic schizophrenic patients who had been drug-free for 3
      weeks and in 17 age- and sex-matched healthy subjects. Plasma concentrations of
      both cytokines were measured again in 12 patients after a 10-week treatment with
      clozapine. Compared with healthy controls, drug-free schizophrenic patients
      exhibited similar plasma IL-6 concentrations, but significantly higher levels of
      TNF alpha. After clozapine treatment, blood concentrations of TNF alpha fell to
      normal levels. These preliminary data support an immune activation in drug-free
      schizophrenic patients and an effect of clozapine on immune parameters.

PMID- 9247978
TI  - Effect of neuroleptic treatment on depressive symptoms in acute schizophrenic
      episodes.
AB  - This study examined depressive symptoms in acute schizophrenic episodes and their
      relationship to neuroleptic treatment. Sixty-three depressed and 62 non-depressed
      acutely exacerbated schizophrenic patients were evaluated with the Brief
      Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, the
      Simpson-Angus Extrapyramidal Scale, and the Hamilton Rating Scale for Depression.
      Subjects were then randomly assigned to different haloperidol plasma levels and
      followed for 3 weeks. Overall, depression improved with treatment of the acute
      psychosis, but a positive association between extrapyramidal side effects and
      depressive symptoms emerged over time. Depressive symptoms tended to be
      positively related to haloperidol plasma levels. The results suggest that
      depressive symptoms in schizophrenia are heterogeneous in origin; while
      neuroleptics can ameliorate depressive symptoms inherent in the acute
      schizophrenic episode, they can also contribute to depression.

PMID- 9247979
TI  - Behavioral, sympathetic and adrenocortical responses to yohimbine in panic
      disorder patients and normal controls.
AB  - Yohimbine, an alpha 2 adrenoreceptor antagonist, enhances norepinephrine (NE)
      release and increases sympathetic activity. We examined the behavioral,
      peripheral sympathetic and adrenocortical responses to oral yohimbine in seven
      healthy controls and 11 patients diagnosed with agoraphobia with panic attacks
      (PD). Patients did not differ in baseline cardiovascular or neuroendocrine
      measures from controls despite significantly higher baseline anxiety ratings.
      Placebo caused no changes in baseline-corrected behavioral, cardiovascular or
      neurochemical responses in either group. Yohimbine induced a panic episode in six
      PD patients, but no controls. PD patients had significantly higher severity
      scores of autonomic anxiety symptoms. Yohimbine significantly raised systolic
      blood pressure (F = 3.07, P < 0.03), plasma NE levels (F = 12.11, P < 0.00) and
      cortisol levels (F = 4.82, P < 0.02), but had no effect on epinephrine levels. NE
      responses were similar in both groups, but patients had higher cortisol responses
      to yohimbine than controls (F = 7.14, P < 0.01). The correlational pattern
      between behavioral ratings and neuroendocrine responses in patients was opposite
      to that observed in controls. Despite similar increases in plasma NE levels
      between PD patients and healthy controls, PD patients had greater anxiogenic,
      cardiovascular and cortisol responses to yohimbine. Enhanced post-synaptic
      adrenoreceptor sensitivity may explain the noradrenergic dysregulation found in
      panic disorder.

PMID- 9247980
TI  - The 35% CO2 challenge test in patients with social phobia.
AB  - Panic disorder (PD) and social phobia (SP) share many clinical, demographic and
      biological characteristics. To investigate the relationships between the two
      disorders, the responses to inhalation of a 35% carbon-dioxide (CO2) and 65%
      oxygen (O2) gas mixture were assessed. Sixteen patients with PD, 16 patients with
      SP, 13 patients with both SP and PD, seven patients with SP who experienced
      sporadic unexpected panic attacks and 16 healthy control subjects inhaled one
      vital capacity of 35% CO2 or compressed air. A double-blind, randomized,
      crossover design was used. PD patients and SP patients showed similar anxiogenic
      reactions to 35% CO2, both stronger than seen in control subjects. Patients with
      both disorders and SP patients with sporadic unexpected panic attacks reacted
      similarly to subjects with PD or SP alone. These results suggest that PD and SP
      share a common hypersensitivity to CO2 and thus might belong to the same spectrum
      of vulnerability.

PMID- 9247981
TI  - Does muscle tension reflect arousal? Relationship between electromyographic and
      electroencephalographic recordings.
AB  - Increased muscle tension and heightened arousal are the most consistent finding
      in patients with anxiety disorders. This study examined the relationship between
      frontalis and gastrocnemius electromyographic (EMG) and electroencephalographic
      activity on 14 female generalized anxiety disorder patients and 14 female control
      subjects. In GAD patients, gastrocnemius but not frontalis EMG was correlated
      with right but not left hemisphere activity. For the non-anxious subjects, there
      was a pattern for both beta 1 and beta 2 waves to be positively associated with
      both frontalis and gastrocnemius muscle tension levels. The results, while
      preliminary, suggest that EMG activity may reflect central nervous system
      arousal.

PMID- 9247982
TI  - Discriminant validity of the Inventory to Diagnose Depression between patients
      with major depression and pure anxiety disorders.
AB  - We examined the discriminant validity of the Inventory to Diagnose Depression
      (IDD), a self-report instrument designed to diagnose major depressive disorder as
      defined in DSM-III-R. Forty patients with major depression (MD), 20 patients with
      anxiety disorders, who had not had a lifetime history of depression (ADs), and 40
      control subjects completed the IDD. The IDD results were compared in the three
      contrasting groups (MD vs. AD+control subjects, MD vs. AD, and MD vs. control
      subjects). The concordance between the IDD and clinical diagnoses, using a
      structured interview, was significantly high in the three groups (k = 0.81, 0.66,
      0.90, respectively). The IDD total score in the MD group was the highest among
      the three groups and was distinguished from the AD group or control group (P <
      0.001, F = 139.9, d.f. = 2,97). However, the IDD occasionally diagnosed subjects
      with AD as having MD.

PMID- 9247983
TI  - Corticosteroid-binding globulin is not decreased in depressed patients.
AB  - We studied corticosteroid-binding globulin (CBG) in 25 drug-free depressed
      patients and 33 healthy controls over a wide age-range. CBG was measured at 0800,
      1400, 2000 and 2400 h in all subjects. Analysis of variance (ANOVA) with repeated
      measurement design revealed a significant effect of gender and time, but not of
      diagnosis (depressed patients vs healthy controls) or age group (< 50/> 50
      years). In females, regardless of diagnosis, CBG plasma concentrations were
      significantly increased, when compared with their male counterparts. Although as
      a group depressed patients had significantly higher plasma cortisol
      concentrations (108.0 +/- 23.1 vs 70.7 +/- 10.9 micrograms/l), CBG levels did not
      differ between the two groups. Thus we did not find hypercortisolemia in
      depression to be paralleled by a decrease in CBG. However, the exaggerated
      activity of the hypothalamus-pituitary-adrenocortical system in healthy and
      depressed females is associated with an increase in plasma CBG.

PMID- 9247984
TI  - Gender identity and role in a pedigree of Arabs with intersex due to 5 alpha
      reductase-2 deficiency.
AB  - Between 1986 and 1995, a pedigree of six Arabs with male pseudohermaphroditism
      due to 5 alpha reductase-2 deficiency have been identified. All, were raised as
      girls since birth. At the time of diagnosis, three were post-pubertal, one
      pubertal and two pre-pubertal. The external genitalia of 'pseudo-vaginal
      perineoscrotal hypospadias' was identical in these subjects. Although these
      individuals were a homogeneous group in terms of their sex of upbringing,
      phenotypic appearance, endocrinological profile and socio-cultural background,
      the development of the gender identity and role was not uniform in these six
      cases. Their psycho-sexual make-up was closely related to the transaction of
      their life experiences. These cases provide further insight into the interaction
      between various factors involved in the development of gender identity and role
      in male pseudohermaphrodites in an Eastern culture.

PMID- 9247985
TI  - Variations of lymphocyte subsets associated with stress in depressive
      populations.
AB  - Major depression and dysthymia have been associated with increased perception of
      day-to-day stressors, greater reliance on emotion-focused coping efforts, and
      reduced perception of uplifting events. Moreover, it has been observed that
      levels of circulating natural killer (NK) cells were elevated in depressed
      patients. Given that mild stressors may increase circulating NK cells, it is
      conceivable that the elevated NK cells in depression may be secondary to the
      increased stress perception associated with the illness. In the present
      investigation a laboratory stressor, comprising a mathematical challenge,
      increased circulating NK cells; however, the extent of the increase was
      comparable in depressive, dysthymic and control subjects. Moreover, the increased
      NK cells induced by the stressor procedure appeared to be independent of
      variations of plasma cortisol, ACTH or norepinephrine. Interestingly, although
      the NK changes were not differentially influenced by stressors in the subject
      populations, in the major depressive patients correspondence existed between NK
      cell levels and emotion-focused coping styles. Likewise, the response to a
      laboratory stressor was directly related to the severity of depression and to the
      use of coping styles involving cognitive restructuring or problem solving.

PMID- 9247986
TI  - Does melatonin have an effect on cognitive performance?
AB  - Exogeneous melatonin causes phase shifts of circadian rhythms, reduces core body
      temperature, and induces drowsiness, but dispute still surrounds the hormone's
      effect on cognitive performance. Using a N = 1 double-blind alternating
      treatments design, daytime performance on four cognitive tests (logical
      reasoning, serial add/subtract, visual-spatial, and four-choice reaction time
      tasks) was measured after PO doses of placebo and 1.6 mg melatonin. Serum
      melatonin and core body temperature were also recorded. Performance was measured
      during time windows corresponding to the serum melatonin peak and the temperature
      trough respectively, following melatonin administration. The data showed that
      performance speed and accuracy measures were not affected during the serum
      melatonin peak, but that reaction times on all cognitive tasks increased
      substantially during the temperature trough. These results suggest that
      circulating melatonin has no direct and immediate effect on cortical information
      processing, and that the reduction in cognitive processing speed during body
      temperature trough occurs as a consequence of the hormone's hypothermic
      properties, causing a slowing down of cerebral processing speed.

PMID- 9247987
TI  - Dose-dependent suppression of adrenocortical activity with metyrapone: effects on
      emotion and memory.
AB  - Different levels of circulating corticosterone are considered to produce
      different emotional states and effects on learning and memory. The purpose of the
      present study was to use different doses of the 11-beta-hydroxylase inhibitor
      metyrapone to produce dose-dependent inhibition of the synthesis of
      corticosterone and examine the consequences of that on several cognitive and
      emotional parameters. Systemic (SC) injections of metyrapone (25 or 50 mg/kg)
      dose-dependently suppressed increases in plasma concentrations of corticosterone
      induced by spatial training in a water maze, but did not affect plasma
      corticosterone levels in non-stressed rats. Treatment with the higher and lower
      dose of metyrapone also differentially affected behavioral measures of emotion
      and memory. Administration of 50 mg/kg, but not 25 mg/kg, of metyrapone impaired
      acquisition performance in the spatial water maze task. Both doses of metyrapone
      impaired retention. The impairment in retention was attenuated by dexamethasone
      (0.3 mg/kg) given systemically immediately after training, but not by
      corticosterone (0.3 mg/kg). During the exposure to a conditioned stressor of
      inescapable footshock, the higher, but not the lower dose of metyrapone
      attenuated fear-induced immobility. In contrast, the lower, but not the higher
      dose attenuated the anxiety state in an elevated plus-maze in a novel environment
      immediately after exposure to the conditioned stressor. It is suggested that
      emotion, learning, and memory are differentially affected by the different doses
      of metyrapone due to interference with different types of adrenal steroid
      receptors and consequent induction of various corticosterone receptor states.

PMID- 9247988
TI  - Blunted dexamethasone-induced growth hormone responses in acute mania.
AB  - Dynamic endocrine testing using a variety of probes has revealed abnormalities of
      the somatotropic axis in bipolar mania. In health, acute administration of
      dexamethasone (DEX) results in the secretion of growth hormone (GH) by possibly
      inhibiting somatostatin tone. We elected to determine DEX/GH responses in acute
      mania. Eight male bipolar manics were compared with eight age-matched healthy
      volunteers. Four milligrams of oral DEX was administered at 0900 h (time 0 min)
      and plasma samples for GH were taken at +60, +180, +240 and +300 min. Baseline
      samples for GH and cortisol were taken at -15 min and 0 min. Patients had higher
      basal cortisol levels (391.6 +/- 89.4 nmol/l) as opposed to controls (138.0 +/-
      13.2 nmol/l) (paired t-test, t = 4.68, df = 6, p < .0004). The mean (+/- SD)
      delta GH (calculated as the maximum GH level relative to baseline) in the manic
      patients was 0.7 +/- 0.8 ng/ml and in the healthy controls was 9.2 +/- 4.3 ng/ml
      (paired t-test, t = -0.589, df = 6, p < .0001). In conclusion, patients with
      bipolar mania had lower DEX-induced GH responses in comparison to controls.

PMID- 9247989
TI  - Aging and work--coping with strengths and weaknesses.

PMID- 9247990
TI  - Finnish research project on aging workers in 1981-1992.
AB  - The objective of this follow-up study of aging workers was to determine changes
      in the work, life-style, health, functional capacity, and stress symptoms of
      Finnish municipal employees from 1981 to 1992. In addition, factors that predict
      improvement or decline in the ability to work were studied. With the use of this
      information, attempts were made to produce practical measures to decrease the
      work-related health risks of elderly workers and increase factors promoting work
      ability. Along with the stress-strain model applied in the study, the reference
      frame of the World Health Organization (WHO) was used. The WHO model emphasizes
      the interaction between work, life-style, aging, and health. Work, life-style,
      health, work ability, and stress symptoms were studied through the use of
      comprehensive questionnaire surveys in 1981, 1985 and 1992. Initially, all the
      subjects (N = 6257) were employed in municipal occupations. During the follow-up,
      the data were supplemented by information on disability to work and mortality.
      The changes in work, life-style, health, work ability, and stress symptoms were
      examined among employees who worked in the same job (N = 924) during the entire
      follow-up period.

PMID- 9247991
TI  - Perceived work changes between 1981 and 1992 among aging workers in Finland.
AB  - OBJECTIVE: Perceived changes in mental and physical work demands and work content
      were evaluated longitudinally. METHODS: Municipal workers (N = 924) in the same
      job from 1981 (mean age 47 years) to 1992 (mean age 58 years) in the work content
      groups of mental, mixed mental and physical, or physical work responded to a
      questionnaire in both 1981 and 1992. RESULTS: The workers reported that the
      physical and mental demands of their jobs had mainly increased from 1981 to 1992,
      especially muscular work and use of knowledge. In 1992 the women still perceived
      higher physical demands than the men but felt they had greater possibilities to
      develop. The use of knowledge had increased, especially among the women, and was
      on the same level for both genders. The perception of changes differed in the 3
      work content groups. CONCLUSIONS: Perceived work demands increase with age.
      Although the 3 work content categories differ somewhat as to perceived changes
      over time, in general, the changes may be more connected to personal factors than
      work factors. Older persons seem to work at a relatively higher capacity than
      younger workers, and this higher work load may be a risk factor for early work
      disability. Work demands and stress factors should therefore be surveyed and
      balanced according to the capacity of the aging worker. On the other hand,
      workers' perception of possibilities to develop seem to increase with age. The
      differences between men and women may especially diminish at a later age.

PMID- 9247992
TI  - Life-style, aging and work ability among active Finnish workers in 1981-1992.
AB  - OBJECTIVES: Life-style is an important factor in explaining the changes in health
      and well-being in old age. In this study life-style was defined according to
      Abel's definition as combining life chances and life conduct. The main question
      concerned the change in life-style components and work ability over a 11-year
      period. METHODS: The study population comprised workers who responded to a
      questionnaire in both 1981 and 1992 and were still working in 1992 (N = 924). The
      changes in the dimensions of life-style (hobbies, living habits, life
      satisfaction) were tested with Pearson's chi-square test. The associations
      between life-style, work ability, and health were analyzed by correspondence
      analysis. RESULTS: Physical activity was the life-style factor that showed a
      major change; it increased among both genders. All other leisure-time activities
      decreased during the follow-up. The women's satisfaction with their life
      situation increased, but the men were less satisfied at the end of the study.
      Work ability, as measured with the work ability index, was a crucial factor in
      these changes. If the work ability remained good, the respondents were also more
      active and more satisfied with their life. This effect of work ability was
      strong, especially with respect to the men's satisfaction with their life
      situation. CONCLUSIONS: Life-style, work ability, and perceived health are highly
      associated, and studying them separately may give a simplistic view of the
      interaction between aging and work. In the future, more comprehensive approaches
      should be applied.

PMID- 9247993
TI  - Aging and changes in health.
AB  - OBJECTIVES: The study explored changes in the health of aging workers from 1981
      to 1992. METHODS: Municipal workers [age 55 to 69 (mean 61.6) years in 1992] who
      filled out questionnaires in both 1981 and 1992 (N = 4534) were studied. The
      changes in disease prevalence and perceived health were tested with Pearson's chi
      square independence test. Improvement and decline in perceived health were
      analyzed by logistic regression models. RESULTS: In 1992, significantly more
      diseases were reported than in 1981; the musculoskeletal disease rate rose from
      38% in 1981 to 53% in 1992 for the women and from 35% to 49% for the men and the
      cardiovascular disease rate rose from 15% in 1981 to 28% in 1992 for the women
      and from 19% to 37% for the men. The age differences diminished during the follow
      up. Self-assessed health improved in all the age groups among both those still
      working in 1992 and those retired. The association between illnesses and
      perceived health changed during the follow-up, 11% of those with no diseases
      experiencing their health as good in 1981 and over 40% in 1992. The most
      important factors explaining the improvement appeared to be a low number of
      physical illnesses and the absence of cardiovascular and musculoskeletal disease.
      Nonphysical work, frequent physical exercise, and satisfaction with life
      situation were also significant contributors to good perceived health.
      CONCLUSIONS: The improvement in perceived health during the follow-up may mean
      that older people have lower criteria for good perceived health than younger
      people do. The associations between self-assessed health and the presence of
      disease need further study.

PMID- 9247994
TI  - Changes in stress symptoms and their relationship to changes at work in 1981-1992
      among elderly workers in municipal occupations.
AB  - OBJECTIVES: This study evaluated perceived changes in stress symptoms and the
      relationship of these changes to work during an 11-year period. METHODS: The
      sample consisted of municipal workers in different occupational groups who had
      remained in the same occupation during 1981-1992 (N = 924, 350 men and 574 women,
      14.8% of the original sample in 1981). The age range was 44-51 years in 1981.
      Changes in the physical and mental stress symptoms and changes at work were
      analyzed with the aid of a structured questionnaire in 1981 and 1992. RESULTS:
      The questionnaire surveys revealed that stress symptoms were markedly increased,
      especially aches and pain in the upper and lower limbs, but also respiratory and
      cardiovascular symptoms. Avoidance reactions, including sense of apathy in
      general and desire to stay at home in the morning, were the most increased
      psychological symptoms. The women experienced a greater increase in symptoms than
      the men. Changes in symptoms were associated with changes at work in that, in
      general, the more symptoms had increased, the more the work had also been
      changed. CONCLUSIONS: The results suggest that the impact of work on the
      functional capacity and symptoms of workers might start even earlier than the age
      of 45 years. This finding is of crucial importance when preventive measures and
      policies are being planned in regard to stress and physical and mental load at
      work. Results on the relationship of changes in cardiorespiratory symptoms and
      work tentatively suggest that, by developing job content and social support, even
      a positive impact on physical symptoms is possible.

PMID- 9247995
TI  - Changes in the work ability of active employees over an 11-year period.
AB  - OBJECTIVES: Changes in the work ability of active employees were followed over a
      period of 11 years. METHODS: Men and women in the same occupation (N = 818) in
      1981-1992 assessed their work ability according to an index on current work
      ability, physical and mental work demands, diagnosed diseases, work impairment
      from disease, sickness absence, work ability prognosis, and psychological
      resources. Their mean initial age was 46.9 (range 44-51) years. The means and
      standard deviations of the work ability index and the prevalence rates of 4 work
      ability categories were followed with respect to age, gender, and job content.
      RESULTS: The mean work ability index declined significantly in 11 years for both
      genders. Its association with age and work was strong. Age of > or = 51 years and
      physical work load were critical factors affecting the work ability of both
      genders. At the mean age of 58 years, at least 25% of the installation,
      auxiliary, or transport workers had a poor work ability rating, as did the women
      doing kitchen supervision, auxiliary, and home care work. The annual rate of
      decline in work ability was highest for women aged 51 years at the onset of the
      study. Female teachers showed a less dramatic decline in work ability than male
      teachers. CONCLUSIONS: Work does not seem to prevent a decline in the work
      ability of men and women as they age. Therefore, measures to promote work ability
      should be started before the age of 51 years, especially for workers in
      physically demanding jobs.

PMID- 9247996
TI  - Aging, work, life-style and work ability among Finnish municipal workers in 1981
      1992.
AB  - OBJECTIVES: This study was designed to explain changes in work ability through
      occupational and life-style factors. METHODS: Work ability was measured by an
      index describing workers' health resources in regard to their work demands. The
      work factors mainly included physical and mental demands, social organization and
      the physical work environment. The life-style factors covered smoking, alcohol
      consumption, and leisure-time physical exercise. The first questionnaire study
      was done in 1981 and it was repeated in 1992. The subjects (N = 818) were workers
      in the 44- to 51-year-old age group in the beginning of the study who were active
      during the entire follow-up. The improvement and, correspondingly, the decline in
      work ability were analyzed by logistic regression models. RESULTS: Both the
      improvement and the decline in work ability were associated more strongly with
      changes in work and life-style during the follow-up than with their initial
      variation. The model for improved work ability included improvement of the
      supervisor's attitude, decreased repetitive movements at work, and increased
      amount of vigorous leisure-time physical exercise. Deterioration in work ability
      was explained by a model which included a decrease in recognition and esteem at
      work, decrease in workroom conditions, increase in standing at work, and decrease
      in vigorous leisure-time physical exercise. CONCLUSIONS: Social relations at work
      can promote or impair the work ability of elderly workers. Although the work
      ability of elderly workers generally declined with aging, both older and younger
      workers were also able to improve their work ability.

PMID- 9247997
TI  - Summary of the Finnish research project (1981-1992) to promote the health and
      work ability of aging workers.

PMID- 9247998
TI  - Both cardiogenic and non-cardiogenic factors are involved in the pathogenesis of
      pulmonary oedema after scorpion envenoming.

PMID- 9247999
TI  - Sir Charles James Martin MB FRS: Australian serpents and Indian plague, one
      hundred years ago.
AB  - In 1891 as Demonstrator in Physiology at the University of Sydney, Charles Martin
      began the first systematic study of the chemical and physiological properties of
      the venoms of the Australian elapid species, Pseudechis porphyriacus and Notechis
      scutatus. Two major constituents were detected: a large coagulable protein which
      was associated with intravascular clotting, and a small proteinaceous molecule,
      an albumose, associated with neurotoxicity. Martin designed and constructed a
      high-pressure gelatin membrane ultrafilter for fractionation of venom. His
      studies indicated that certain physiological actions and clinical symptoms were
      related to the faster rate of diffusion within the tissue space of a neurotoxic
      constituent relative to a clotting constituent. Extending this work to toxin
      antitoxin relationships, Martin provided evidence that antitoxin was a large
      molecule with slow diffusibility in tissue and advised the administration of
      curative serum (including diphtheria antitoxin) by intravenous injection. In
      1903, Martin returned to London as Director of the Lister Institute of Preventive
      Medicine. He was soon involved in the planning of scientific work to be
      undertaken by the Commission for Investigation of Plague in India as the disease
      continued to ravage the subcontinent. Detailed epidemiological studies of
      possible factors involved in the spread of Pasteurella pestis showed,
      unequivocally, that infected rat fleas were the vector of transmission from rats
      to humans.

PMID- 9248000
TI  - Botulinolysin, a thiol-activated hemolysin produced by Clostridium botulinum,
      inhibits endothelium-dependent relaxation of rat aortic ring.
AB  - The effects of botulinolysin (Blyn), a thiol-activated hemolysin produced by
      Clostridium botulinum, on contractility of rat aortic ring were studied in order
      to clarify an underlying mechanism of vasoconstriction by the toxin observed
      previously as an increase in perfusion pressure in isolated rat organs. Blyn (30
      hemolytic units/ml; HU/ml) itself did not elicit any apparent change in resting
      tension of the ring. Contractile tension elicited by a high concentration of
      phenylephrine in endothelium-intact rings increased significantly after treatment
      with Blyn (30 HU/ml), while phenylephrine-induced contraction of endothelium
      denuded rings was not influenced by toxin treatment. In rings with intact
      endothelium, acetylcholine (ACh)-induced relaxation was significantly inhibited
      after treatment with Blyn (30, 10, 1 HU/ml). In contrast, relaxation of denuded
      rings by sodium nitroprusside was not affected by toxin treatment (30 HU/ml).
      Arginine (10(-4) M) partly reversed the inhibition of ACh-induced relaxation by
      the toxin (1 HU/ml). Endothelium-dependent relaxation by histamine or adenosine
      triphosphate was also inhibited by Blyn (1 HU/ml), but the relaxation elicited by
      calcium ionophore A23187 was not influenced by the toxin. The results indicate
      that Blyn acts on endothelium and inhibits agonist-induced endothelium-dependent
      relaxation of blood vessels.

PMID- 9248001
TI  - The CDNA and genomic DNA sequences of a mammalian neurotoxin from the scorpion
      Buthus martensii Karsch.
AB  - The cDNA library of venomous glands of the scorpion Buthus martensii Karsch (BmK)
      was constructed. A cDNA encoding a mammalian neurotoxin corresponding to the
      known alpha-type toxin, BmK M1, was amplified by polymerase chain reaction (PCR)
      and cloned, and its full-length sequence was determined. The open reading frame
      encoded the precursor of BmK M1 with 84 amino acid residues, including a signal
      peptide of 19 residues, a mature toxin of 64 residues and an additional C
      terminal residue Arg which might be cleaved off by proteinase postprocessing
      immediately after protein synthesis. Based on the determined cDNA sequence and
      using the total DNA of the scorpion as a template, the gene of BmK M1 was also
      amplified by PCR and sequenced. The genomic DNA sequence revealed an intron of
      408 base pairs present within the signal peptide region. Both the intron and exon
      of BmK M1 share about 75% similarity with those of AaH I' another alpha-type
      mammalian neurotoxin in the scorpion Androctonus australis Hector.

PMID- 9248002
TI  - Stability of microcystins from cyanobacteria--IV. Effect of chlorination on
      decomposition.
AB  - Microcystins, the cyclic heptapeptide toxins produced by cyanobacteria such as
      Microcystis, show tumor-promoting activity through inhibition of protein
      phosphatases 1 and 2A. They potentially threaten human health, and are increasing
      the world-wide interest in the health risk associated with cyanobacterial toxins.
      In this study, the effect of chlorination on the decomposition of microcystins-LR
      and -RR was examined. The toxins were easily decomposed by chlorination with
      sodium hypochlorite, and the decomposition depended on the free chlorine dose. In
      this operation, many reaction products were formed, one of which was determined
      to be dihydroxymicrocystin formed through the chloronium ion at the conjugated
      diene of Adda [3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E), 6(E)
      dienoic acid], followed by hydrolysis. Other products may be its stereoisomers
      and/or regioismers. No noxious products were detected from the chlorination
      process of microcystin-LR. Although these results suggested that chlorination at
      an adequate chlorine dose is very effective for the removal of microcystin in raw
      water, preoxidation of the cell itself with chlorine must be avoided, because it
      frequently causes toxin release from algae and produce trihalomethanes during
      water treatment.

PMID- 9248003
TI  - Isolation and characterization of a new clotting factor from Bothrops jararacussu
      (jararacucu) venom.
AB  - A detailed procedure for the isolation of a new clotting enzyme from the venom of
      Bothrops jararacussu (common name jararacucu) is described. The estimated mol. wt
      of the native protein was 30,100 but 37,500 after reduction by dithiothreitol.
      Two major close bands corresponding to pI 5.18 and 5.20 were detected by
      electrofocusing but, after methanolysis, a single band focused at pI 8.20. The
      mol. wt of the protein moiety of this glycoprotein was 28,500, showing V-V-G-A-D
      N-C-N-F-N... as N-terminal sequence. The content of neutral sugar was 4.8% and
      that of total sugars 5.3%. This clotting factor degraded only the A alpha-chain
      of the fibrinogen molecule. The stability of the clot, when produced in the
      presence of aprotinin opens new uses for snake clotting enzymes in the production
      of fibrin glue.

PMID- 9248004
TI  - Biochemical and histopathological alterations induced in rats by Tityus
      serrulatus scorpion venom and its major neurotoxin tityustoxin-I.
AB  - Intravenous injection into the rat of sublethal doses of Tityus serrulatus
      scorpion venom (100 micrograms protein/kg) or its major neurotoxin tityustoxin-I
      (TsTX-I, 20 micrograms/kg) caused, 30-180 min after injection, statistically
      significant increases in the serum levels of aspartate aminotransferase, amylase,
      creatine kinase and lactate dehydrogenase, as well as hyperglycemia, a high level
      of plasma free fatty acids and a low level of liver glycogen. The in vitro serum
      levels of the above enzymes did not change. For alanine aminotransferase, gamma
      glutamyl transferase and alkaline phosphatase, neither in vitro nor in vivo
      alterations were observed. The whole venom and TsTX-I caused hepatic congestion
      with hemolysis and hydropic degeneration. Other histological lesions included
      edema and congestion with subpleural hemorrhage in the lungs, hypertrophy of
      fibers with degeneration areas in the heart, and congestion and hemorrhage in the
      kidneys. In the salivary glands, alterations to the acini and ductules were
      visible. In the adrenal glands no morphological alterations could be detected at
      the studied doses. The results suggest that the in vivo enzymatic and
      histopathological alterations are due to tissue lesions evoked by the whole venom
      and TsTX-I. An indirect effect, however, induced by stimulation of acetylcholine
      and catecholamine release in the postganglionic nerve terminals, cannot be
      excluded.

PMID- 9248005
TI  - Action of babycurus-toxin 1 from the east African scorpion Babycurus
      centrurimorphus on the isolated cockroach giant axon.
AB  - A toxin named babycurus-toxin 1 (mol. wt 8191), from telson extracts of the
      scorpion Babycurus centrurimorphus, was found to depolarize the cockroach giant
      axon. It progressively blocked the evoked action potentials after a short period
      of limited repetitive activity and after 30 min of toxin action it became
      impossible to evoke responses to current stimulations. Voltage-clamp experiments
      on the sodium current indicated that the toxin in micromolar concentrations
      progressively decreased the transient inward peak sodium current, but also slowed
      the activation phase of this sodium current and maintained an inward current
      during the voltage pulses, which deactivated slowly. The toxin also induced in
      the insect axon a slowly activating-deactivating component of the sodium current.
      This suggests that the toxin modifies both activation and inactivation mechanisms
      of sodium channels. Thus there is some similarity in the electrophysiological
      effects between BcTx1 and the beta-toxins active on mammals.

PMID- 9248006
TI  - Occurrence of paralytic shellfish poison in the starfish, Asterias amurensis in
      Kure Bay, Hiroshima Prefecture, Japan.
AB  - In May 1996, during surveillance on the toxicity of invertebrates such as
      bivalves inhabiting the coasts of Hiroshima Bay, the starfish Asterias amurensis
      collected in the estuary of the Nikoh River was found to contain toxins which
      showed strong paralytic action in mice; the maximum toxicity (as paralytic
      shellfish poison, PSP) was 8.0 MU/g for whole body and 28.7 MU/g for viscera
      throughout the monitoring period, March to July 1996. Attempts were made to
      identify the paralytic toxins in the starfish. They were extracted with 80%
      ethanol acidified with acetic acid, followed by defatting with dichloromethane.
      The aqueous layer obtained was treated with activated charcoal and then applied
      to a Sep-Pak C18 cartridge. The unbound toxic fraction was analyzed by high
      performance liquid chromatography techniques. The starfish toxin was rather
      unexpectedly identified as PSP. It was comprised of high toxic components
      (gonyautoxin-1; GTX1, GTX2, GTX3, GTX4, decarbamoyl-GTX3; dcGTX3 and dcSTX) as
      the major components, which accounted for approximately 77 mole% of all
      components, along with protogonyautoxin-1, 2, 3 and 4 (PX1-4), which are N
      sulfocarbamoyl derivatives. Of the high toxic components, GTX1 was present in the
      largest amounts. It was concluded that the toxin of starfish collected in the
      estuary of Nikoh River in May 1996 consisted of PSP, which supposedly came via
      the food chain from toxic bivalves living in the same area. To our knowledge,
      this is the first report of the occurrence of PSP in starfish.

PMID- 9248007
TI  - Protection by the heavy metal chelator N,N,N',N'-tetrakis (2
      pyridylmethyl)ethylenediamine (TPEN) against the lethal action of botulinum
      neurotoxin A and B.
AB  - The ability of N,N,N',N'-tetrakis (2-pyridylmethyl)-ethyenediamine (TPEN) to
      protect against botulinum neurotoxin (BoNT) A and B was examined in vivo in mice.
      To determine the protective efficacy of TPEN, mice were injected i.p. with TPEN
      as a single bolus or as multiple injections 30 min before and 0, 2, 4 and 6 hr
      following i.v. challenges with BoNT-A or -B. TPEN treatment did not alter the 24
      hr lethality of BoNT but did produce a significant delay in the time to death.
      For a moderate dose of serotype A (20 LD50), five divided doses of TPEN prolonged
      the time to death from 7.8 +/- 0.4 hr to 9.9 +/- 0.5 hr. For serotype B, examined
      under comparable conditions, the prolongation of the time to death was from 6.1
      +/- 0.2 hr to 9.4 +/- 0.6 hr. The range of TPEN doses that could be examined in
      vivo was limited by its acute toxicity. Although low doses of TPEN (< or = 10
      mg/kg) were well tolerated, higher doses (> or = 30 mg/kg) led to ataxia, loss of
      coordination, convulsions and death in 20.3 min or less. In clonal NG108-15
      cells, TPEN was found to produce cytotoxicity as revealed by increases in the
      secretion of the marker enzyme lactate dehydrogenase (LDH), and enhanced
      reactivity with the vital dye trypan blue. From LDH concentration-response data
      determined 24 hr after addition of TPEN, the threshold concentration for
      observing cytotoxicity was 10 microM and the IC50 was 19.8 microM. At the highest
      TPEN concentration tested (100 microM), cytotoxicity was detected 8 hr after TPEN
      addition and increased in severity over a 3 day period. The cytotoxicity in NG108
      15 cells appears to be distinct from the rapid-onset toxicity observed in whole
      animals. These results suggest that TPEN may be of potential benefit in delaying
      the lethal actions of BoNT-A and -B, but its use is limited by its initial and
      delayed toxicity. Since the therapeutic and toxic actions of TPEN are both
      related to zinc chelation, the use of TPEN would need to be restricted to low
      doses as part of a combination therapy.

PMID- 9248008
TI  - An in vitro pharmacological examination of venom from the soldierfish Gymnapistes
      marmoratus.
AB  - The aim of the present study was to commence a characterisation of some of the
      basic pharmacological properties of venom from the soldierfish (Gymnapistes
      marmoratus). Soldierfish venom was prepared by extraction into 10% glycerol and
      centrifugation to remove insoluble material. Protein content was determined and
      venom concentrations were expressed as microgram venom protein. Soldierfish venom
      (0.5-15 micrograms/ml) produced concentration-dependent contractile responses in
      guinea-pig isolated ileum (GPI) and longitudinal smooth muscle (LSM)
      preparations. The muscarinic receptor antagonist atropine (10 nM) significantly
      inhibited responses of LSM to soldierfish venom (2.5 micrograms/ml). Responses to
      soldierfish venom (4-5 micrograms/ml) in GPI were not significantly affected by
      the ganglion-blocking drug mecamylamine (10 microM) or by incubation with blood
      cholinesterase. The cyclooxygenase inhibitor indomethacin (2 microM)
      significantly inhibited responses to soldierfish venom (2.5 micrograms/ml) in
      LSM. Neither the thromboxane A2/prostaglandin H2 receptor antagonist GR32191B (1
      microM) nor the leukotriene receptor antagonist SB205312 (10 nM) significantly
      affected responses to soldierfish venom (5 micrograms/ml) in GPI. Responses to
      soldierfish venom (2.5-5 micrograms/ml) were not significantly inhibited by the
      histamine receptor antagonist mepyramine (0.5 microM), the angiotensin-converting
      enzyme inhibitor captopril (2 microM) or the neurokinin-1 receptor antagonist CP
      99,994 (0.1 microM) in LSM. The angiotensin AT1 receptor antagonist EXP3174 (0.1
      microM) also failed to inhibit significantly the responses to soldierfish venom
      (5 micrograms/ml) in GPI. A fluorometric assay for the detection of 5
      hydroxytryptamine (5-HT) and related compounds indicated a level in soldierfish
      venom of 1.60 +/- 0.01 ng of 5-HT-like substance per microgram venom protein.
      Soldierfish venom (0.5-10 micrograms/ml) produced concentration-dependent
      contractile responses in rat isolated stomach fundus strips, and these responses
      (2.5 micrograms/ml) were significantly inhibited by the 5-HT1/5-HT2 receptor
      antagonist methysergide (0.1 microM). These results suggest that soldierfish
      venom may stimulate the release of acetylcholine to act at muscarinic receptors
      on guinea-pig gastrointestinal smooth muscle. The venom also appears to be
      causing the release of cyclooxygenase products, such as prostaglandins, and
      contains 5-HT, or a 5-HT-like substance, that acts directly at 5-HT receptors.

PMID- 9248009
TI  - The action of Taiwan cobra venom on methionine enkephalin: a useful assay for
      oligopeptidase content.
AB  - The pentapeptide methionine enkephalin is readily hydrolysed by the
      oligopeptidase activity contained in Taiwan cobra (Naja naja atra) venom. It is a
      significantly better substrate than the peptides previously used to identify the
      presence of this enzyme, but it retains many of the sequence characteristics
      shared by these other peptides. Analysis of the manner of hydrolysis by means of
      high-performance liquid chromatography and electrospray mass spectrometry
      revealed the simultaneous actions of at least two types of oligopeptidase on the
      neuropeptide, producing two routes of initial breakdown. By one route, an
      endopeptidase cleaved the Gly-Phe bond of enkephalin first to release Tyr-Gly-Gly
      and Phe-Met. By the other route, an aminopeptidase was able to release Tyr and
      Gly-Gly-Phe-Met by cleaving the Tyr-Gly bond first. From amongst the various
      peptide fragments produced, Tyr-Gly-Gly was subject to immediate aminopeptidase
      action to release Tyr and Gly-Gly. The free Tyr produced in these reactions was
      in turn quickly transformed by the L-amino acid oxidase in the venom. The kinetic
      qualities of the enkephalin hydrolysis, and the conversions of the fragments Tyr
      Gly-Gly and Tyr, were measured. Methionine enkephalin has potential as a routine
      assay for venom oligopeptidases, either in testing the venoms from other species
      or in attempts to purify these enzymes. Moreover, the ease of hydrolysis of this
      bioactive peptide, coupled with the revelation of the other enzymic steps
      involving the fragments generated, may provide important clues as to the possible
      role of the oligopeptidases (and L-amino acid oxidase) in the venom.

PMID- 9248010
TI  - BRS1, a C30 bis-amino, bis-hydroxy polyunsaturated lipid from an Australian
      calcareous sponge that inhibits protein kinase C.
AB  - In the course of screening for activity at the phorbol ester binding site of
      protein kinase C, activity was identified within an unidentified calcareous
      sponge (class Calcarea) collected in the central region of the Great Barrier Reef
      off the north-east coast of Australia. Using high-performance liquid
      chromatographic fractionation guided by activity at the enzyme, the C30
      polyunsaturated lipid was isolated and its structure assigned on the basis of
      spectroscopic analysis. The compound was given the trivial name BRS1. It
      exhibited a 50% effective concentration for inhibiting phorbol ester binding of 9
      microM and for inhibiting enzymic activity of 98 microM. This compound represents
      a novel protein kinase C inhibitor.

PMID- 9248011
TI  - Absence of skin alkaloids in captive-raised Madagascan mantelline frogs
      (Mantella) and sequestration of dietary alkaloids.
AB  - Mantelline frogs of the genus Mantella contain a variety of pumiliotoxin,
      allopumiliotoxin and homopumiliotoxin alkaloids in their skin. Pyrrolizidines,
      indolizidines and quinolizidines are also present. In contrast, captive-raised
      frogs (Mantella aurantiaca) have no alkaloids detectable in skin extracts. Frogs
      fed alkaloid-dusted fruit flies accumulate alkaloids into their skin. Thus, these
      mantelline frogs, like the neotropical dendrobatid frogs, appear dependent on
      dietary sources for their skin alkaloids and have the requisite alkaloid
      sequestering system(s).

PMID- 9248012
TI  - Specificity of the test based on modification of cell morphology for detection of
      lipophilic inhibitors of protein phosphatases.
AB  - The test based on morphological changes in KB cells was assayed with different
      toxins. Only lipophilic inhibitors of protein phosphatases, such as okadaic acid
      or calyculin A, induced visible changes in cell morphology. The activity of
      contaminated mussel extracts on KB cells was evaluated comparatively by direct
      interpretation of morphological changes and by a colorimetric method estimating
      the number of viable cells after staining. The latter technique revealed
      interferences (not detected by the former) with mussel cytotoxins. These results
      show that the technique, based on determination of the minimal active
      concentration of toxic extracts inducing morphological changes, is more specific,
      faster and preferable to the determination of IC50 for the detection of protein
      phosphatase inhibitors in shellfish.

PMID- 9248013
TI  - Enzymatic properties of the Duvernoy's secretion of Blanding's tree snake (Boiga
      blandingi) and of the mangrove snake (Boiga dendrophila).
AB  - Duvernoy's secretion from representatives of the colubrid genus Boiga has been
      shown by other workers: (1) to contain an alpha-bungarotoxin-like component
      (Blanding's tree snake, Boiga blandingi); (2) to exhibit acetylcholine receptor
      binding activity (the brown tree snake, Boiga irregularis); and (3) to react
      strongly (B. blandingi and the mangrove snake, Boiga dendrophila) with antisera
      raised against elapid venoms. The present study provides the first evidence for
      the presence of acetylcholinesterase, a common elapid enzyme, in the Duvernoy's
      secretion of B. dendrophila and B. blandingi at levels of 122 +/- 7 and 0.36 +/-
      0.02 International Enzyme Units, respectively. Constants for inhibition by
      eserine were 1.25 x 10(-7) M and 2.79 x 10(-7) M, respectively. The Duvernoy's
      secretion of B. dendrophila exhibited significant phospholipase and haemolytic
      activities, whereas phosphodiesterase was only weakly present and no thrombin
      like activity was observed.

PMID- 9248014
TI  - Venom of a six-eyed crab spider, Sicarius testaceus (Purcell, 1908), causes
      necrotic and haemorrhagic lesions in the rabbit.
AB  - By employing haematological, histological and isotope studies on rabbit, it was
      shown that envenomation by the South African crab spider, Sicarius testaceus,
      results in tissue necrosis and a marked increase in the permeability of the blood
      vessels in the vicinity of envenomation. The venom also acts systemically, which
      results in petechial bleeding of some viscera, thrombocytopaenia and elevated
      fibrinogen levels. Rabbit envenomation by this species results in a dramatic drop
      of the platelet count, without haemolytic anaemia. Should these parameters be the
      same in humans, they may serve as a yardstick to distinguish presumptive S.
      testaceus envenomation from that of Loxosceles.

PMID- 9248015
TI  - Bibliography of toxinology.

PMID- 9248016
TI  - Serodiagnosis of sarcoptic mange in pigs.
AB  - A serodiagnostic test (ELISA) for detecting antibodies to Sarcoptes scabiei in
      the sera of pigs was evaluated. The ELISA results from 221 specific pathogen-free
      pigs of three different age categories were used to establish a cut-off value for
      the assay. Background optical density values differed significantly between the
      three groups, the sows having the highest values. The mean + 3 sd of their values
      was chosen as the cut-off. Four farrow-to-finish herds of pigs with sarcoptic
      mange were investigated. Skin scrapings were taken from each animal for the
      demonstration of S scabiei and their sera were assayed for the presence of
      antibodies to the mite. All the herds had active infections with S scabiei and
      antibodies to S scabiei were found in a significant number of the animals
      sampled. The sensitivity and specificity of the ELISA were 87.8 and 99.5 per
      cent, respectively, employing clinical diagnosis as the gold standard. A higher
      sensitivity (100 per cent), but a lower specificity (32.8 per cent) was obtained
      when the results of skin scrapings were used as the gold standard.

PMID- 9248017
TI  - Ultrasonographic findings in cattle with pleuropneumonia.
AB  - The clinical, ultrasonographic and radiographic findings in three cows and one
      bull with pleuropneumonia are described. All the animals had fever, indigestion,
      tachypnoea and abnormal lung sounds. Percussion of the thoracic wall elicited
      signs of pain and tests for foreign bodies were positive. Ultrasonographic
      examination revealed an accumulation of anechogenic to hypoechogenic fluid in the
      pleural space in the ventral thorax of all the animals. In one animal, echogenic
      bands of fibrin were observed between the thoracic wall and pulmonary surface. In
      another, parts of the right lung were not inflated because of severe
      bronchopneumonia. Radiographic examination revealed a pleural effusion, apparent
      as a horizontal fluid line, in three animals. In addition, the increased
      radiopacity in parts of the dorsal lung fields and increased bronchial and
      peribronchial markings suggested bronchopneumonia. In three animals, the
      radiographs revealed linear foreign bodies in the reticulum, suggesting that the
      pleuropneumonia was caused by the penetration of the foreign body into the
      thoracic cavity. A diagnosis of pleuropneumonia was made in all the animals on
      the basis of the clinical, ultrasonographic and radiographic findings and the
      analysis of the pleural fluid. The diagnosis was confirmed at slaughter in three
      of them; the fourth animal was treated and was clinically healthy when it was
      discharged.

PMID- 9248018
TI  - Ageing draft and trotter horses by their dentition.
AB  - The accuracy of ageing horses by their dentition was assessed by comparing the
      dental features with the known dates of birth of 212 trotter horses and 189
      Belgian draft horses. The horses ranged in age from two to 25 years. In both
      breeds it was observed that the shedding of the incisors and the appearance of
      the dental stars were the most reliable features for age determination. In young
      animals, the dental configuration was similar in both breeds. With increasing age
      the incisor teeth of draft horses were more liable to abrasion than those of
      trotter horses. The sequential changes in appearance of the permanent incisors
      occurred earlier in draft horses than in trotters.

PMID- 9248019
TI  - Uterus unicornis in two mares.

PMID- 9248020
TI  - Control of sheep scab.

PMID- 9248021
TI  - Control of sheep scab.

PMID- 9248022
TI  - Antibiotic resistance.

PMID- 9248023
TI  - Virulent foot rot in sheep.

PMID- 9248024
TI  - Virulent foot rot in sheep.

PMID- 9248025
TI  - Neurological condition in polled Dorset lambs.

PMID- 9248026
TI  - Abdominal distension in a cat.

PMID- 9248027
TI  - Calcipotriol poisoning in dogs.

PMID- 9248029
TI  - Art and science of veterinary medicine.

PMID- 9248028
TI  - Chocolate poisoning in dogs.

PMID- 9248030
TI  - A field deployable gas chromatograph/mass spectrometer for industrial hygiene
      applications.
AB  - To study the feasibility and efficacy of field gas chromatograph/mass
      spectrometers (GC/MS), the National Institute for Occupational Safety and Health
      (NIOSH) conducted laboratory and field testing of a commercial transportable
      GC/MS. That unit was reengineered and reconstructed by NIOSH as a more portable
      GC/MS (can be moved, set up, and operated by one person), incorporating novel
      weight and size-reducing vacuum technology. Further laboratory and field tests
      were then accomplished. This NIOSH-developed vacuum technology has proven
      important in reducing the size and weight of the GC/MS by up to 50%, making it
      much more suitable for field use. Experience has shown that for a large class of
      survey situations involving monitoring of components of complex mixtures of
      vapors and gases field use of GC/MS can be very useful.

PMID- 9248031
TI  - Effect of altered vision on constant load exercise performance while wearing a
      respirator.
AB  - Previous testing has shown that visual acuity greatly influences task performance
      at light work rate levels. At moderate to heavy work rates, however, the
      Performance Rating Table (PRT) predicts almost no visual acuity effect. This
      experiment was performed to determine if the PRT value is realistic. Ten subjects
      walked on a treadmill at 75-80% of their maximum heart rates until their
      voluntary end points. Subjects wore various masks of the same kind, each with a
      different set of clouded lenses. Visual acuities, as measured on the Snellen eye
      chart, were measured before, during, and after exercise. It was found that visual
      acuity did not influence performance time, and that an average value for a
      performance rating of 91 must have been influenced by other mask factors besides
      visual acuity. These other factors are most likely respiratory stress, thermal
      stress, and other vision elements. The full-facepiece masks used in this study
      adversely affected visual acuity by about three-quarters of a Snellen line during
      exercise. Postexercise visual acuities were found to first decrease below pre
      exercise values, then become better than pre-exercise values, then decline
      asymptotically to pre-exercise values.

PMID- 9248032
TI  - Airborne aflatoxin in the grain processing industries in India.
AB  - Airborne aflatoxin generated in rice and maize processing plants was assayed by
      an indirect competitive enzyme-linked immunosorbent assay. In the rice mill,
      levels of airborne aflatoxin were always higher in the respirable dust samples (<
      7 microns) compared with the total dust samples (< 7 microns). The concentrations
      of total airborne aflatoxin in the respirable dusts were 26 picogram/m3 and 19
      pg/m3, respectively, for the workplace and the storage area of the rice mill,
      while the concentrations of total dust were 12 pg/m3 for the workplace and 11
      pg/m3 for the storage area. Airborne aflatoxin was not detected in control sites
      of either of the grain processing plants or from the total dust samples obtained
      from the maize plant. Three sites in the maize processing plant-the elevator (18
      pg/m3), the loading/unloading area (800 pg/m3), and the oil mill (816 pg/m3)
      showed the presence of airborne aflatoxin only in the respirable dust samples.

PMID- 9248033
TI  - Workers exposed to thermal degradation products of TDI- and MDI-based
      polyurethane: biomonitoring of 2,4-TDA, 2,6-TDA, and 4,4'-MDA in hydrolyzed urine
      and plasma.
AB  - The aim of the study was to investigate biomarkers of exposure to thermal
      degradation products of 2,4- and 2,6-toluene diisocyanate (TDI)- and 4,4'
      methylenediphenyl diisocyanate (MDI)-based polyurethane and the toxicokinetics of
      these products. Blood and urine were collected from 15 factory workers exposed to
      thermal degradation products of MDI-based polyurethane glue and TDI-based
      flexible foam. Four of these workers were also studied during an exposure-free
      period. Urine and plasma were analyzed after acidic hydrolysis and the
      concentrations of the isocyanates' corresponding amines, 2,4-, 2,6-toluenediamine
      (TDA), and 4,4'-methylenedianiline (MDA), were determined as derivatives of
      pentafluoropropionic anhydride by gas chromatography using chemical ionization
      mass spectrometry monitoring negative ions. Urinary elimination rates were in the
      range of < 0.01-5.7 micrograms of 2,4-TDA per hour, < 0.01-3.5 micrograms of 2,6
      TDA per hour, and < 0.01-1.6 micrograms of 4,4'-MDA per hour. Plasma levels were
      in the range of < 0.1-5.5 ng of 2,4-TDA per mL, < 0.1-2.3 ng of 2,6-TDA per mL,
      and < 0.1-45 ng of 4,4'-MDA per mL. The urinary half-lives of 4,4'-MDA for four
      of the workers were found to be 59, 61, 73, and 82 hours. The half-lives of 4,4'
      MDA in plasma were 10, 14, 16, and 22 days. Elimination rate peaks of 2,4-TDA,
      2,6-TDA, and 4,4'-MDA in urine varied during and between workdays. The individual
      variation in plasma concentrations of 2,4-TDA, 2,6-TDA, and 4,4'-MDA with time
      was small, but between individuals the variation was great.

PMID- 9248034
TI  - PCR and sero-diagnosis of chronic Chagas' disease. Biotechnological advances.
AB  - In the acute phase of Chagas' disease, when the parasitemia is high, diagnosis
      can be easily made using conventional parasitological methods. During the chronic
      phase, due to the low parasitemia, diagnosis is performed mainly by immunological
      methods. Conventional serological techniques are limited by cross-reactivity with
      other parasitic diseases, non-standardization of reagents, and the diversity of
      technical procedures. Methods are being developed to improve the sensitivity and
      specificity of diagnosis using molecular approaches. PCR-based detection systems
      and the use of recombinant antigens in ELISA are the most promising.

PMID- 9248035
TI  - Construction and characterization of a biotin-regulated gene expression system in
      Escherichia coli.
AB  - An autoregulated gene expression system in Escherichia coli was designed such
      that the cloned genes on the vector were not expressed until biotin was depleted
      during cell growth. The expression vectors were constructed by assembling the DNA
      fragments containing the regulatory region of the E. coli biotin operon (bio
      operon), the universal ribosome-binding site (RBS) and the strong transcription
      terminator rrnBT1T2. The promoter region was further modified by site-directed
      mutagenesis to create promoters of varied strength. The feasibility of this
      system was examined in E. coli strain R901 (with bio operon deleted) using
      various marker genes, including the E. coli birA gene, T7 RNA polymerase gene and
      yellowfin-porgy growth-hormone gene. The results demonstrated that the induction
      of marker-gene expression can be triggered as the biotin concentration drops to a
      threshold value of approximately 2 ng/mL by metabolic utilization.

PMID- 9248036
TI  - Enzymic activity of whole cells entrapped in reversed micelles. Studies on alpha
      amylase and invertase in the entrapped yeast cells.
AB  - Studies have been conducted on the enzymic activity of Baker's yeast and also of
      Brewer's yeast entrapped into the reversed micelles formed by cetyl pyridinium
      chloride (CPC1) in n-hexane. The activities of alpha-amylase and invertase
      enzymes in the entrapped cells have been estimated and compared with those in the
      control experiments where there was no entrapment. The following significant
      observations have been made: 1. except for invertase, enzymes in Brewer's yeast,
      the entrapped yeast cells showed enhanced enzymic activities; 2. when the yeast
      cells were entrapped inside the reversed micelles along with substrates of the
      two enzymes, alpha-amylase, and invertase, the activity of each of these enzymes
      showed a further enhancement in comparison to that showed in the experiments in
      which substrates of the individual enzymes alone were entrapped-the phenomenon of
      synergism; 3. when the yeast cells and the respective substrates were entrapped
      inside separate reversed micelles and the solutions containing entrapped cells
      and entrapped substrates were mixed, the activities of the individual enzymes,
      alpha-amylase and invertase, showed further enhancement in comparison to the case
      in which the cells and the substrates were entrapped inside the same reversed
      micelle (in this case also the phenomenon of synergism was observed); and (4) In
      the case of experiments in which there was no entrapment, it was observed that
      the presence of substrates induced more release of enzymes from the yeast cells.
      These observations on yeast cells, which to the best of our knowledge have not
      been reported before, should be biotechnologically relevant.

PMID- 9248037
TI  - DNA recommendations--further report of the DNA Commission of the ISFH regarding
      the use of short tandem repeat systems.

PMID- 9248038
TI  - Considerations from the European DNA profiling group (EDNAP) concerning STR
      nomenclature.

PMID- 9248039
TI  - Evaluation of post-mortem oxymetry with reference to the causes of death.
AB  - We examined blood samples of 214 forensic autopsy cases, excluding fire victims,
      on a CO-oximeter system in order to evaluate post-mortem oxymetric profiles with
      reference to the causes of death. Oxyhemoglobin (O2-Hb) levels in the left and
      right heart blood, respectively, ranged from 0 to 97.7% and from 0 to 92.1%,
      showing no apparent correlation with the post-mortem intervals or rectal
      temperatures. In nearly 60% of the cases, O2-Hb was lower than 10%. A high O2-Hb
      level (over 50%) in the left heart blood was most frequently observed in death
      from cold exposure and occasionally in fatalities from blunt injuries and
      stab/incised wounds with or without medical care. O2-Hb in the heart blood was
      usually very low (under 10%) in fatalities from asphyxiation, drowning, poisoning
      and natural diseases. A greatest oxymetric variation was observed in death from
      injuries, probably due to varied causal mechanisms of death. In most cases, the
      differences between blood O2-Hb levels in the heart and iliac vessels were within
      15%; whereas O2-Hb in the cerebral venous blood was usually evidently higher than
      that in the right heart blood. An inverse relation of O2-Hb levels to total
      hemoglobin contents was observed slightly for the blood in the heart and iliac
      vessels, and more obviously for the cerebral venous blood. The above post-mortem
      oxymetric profiles were considered to at least partially reflect the final
      balance of oxygen uptake and consumption in dying process, possibly also affected
      by the circulatory status, giving an objective index to the color of cadaveric
      blood (hypostasis), although it should be assessed in consideration of post
      mortem interference and total hemoglobin contents. In any case, however, post
      mortem oxymetry seemed to have a limited value owing to severe systemic hypoxia
      which would be a common final state before death from various fatal traumas and
      diseases, maybe except for those with extremely short agony.

PMID- 9248040
TI  - A genetic study of the short tandem repeat systems VWA and TH01 in an Austrian
      population.
AB  - Allele- and genotype frequencies of the two short tandem repeat (STR) systems VWA
      and TH01 were determined in an Austrian population sample by polymerase chain
      reaction (PCR) analysis. A total of 9 alleles for VWA and 6 alleles for TH01
      could be observed in a population of 278 (VWA) and 276 (TH01) individuals. Both
      systems are in accordance with Hardy-Weinberg equilibrium. They are highly
      informative for individualization from stain analysis and, in addition, they are
      very useful for paternity testing. The data presented here allow the statistical
      interpretation of PCR results for an Austrian population.

PMID- 9248041
TI  - A possible chemical explanation for the events associated with the death of
      Gloria Ramirez at Riverside General Hospital.
AB  - The events associated with the death of Gloria Ramirez at Riverside General
      Hospital on 19 February 1994 have been portrayed as a major medical mystery. A
      potential chemical explanation for this incident has been developed. The
      hypothetical scenario depends upon the oxidation of a common solvent, dimethyl
      sulfoxide, through dimethyl sulfone to dimethyl sulfate. The latter compound is a
      volatile and highly toxic agent that can be quite hazardous to humans in small
      amounts. It is also environmentally nonpersistent. Much of the mystery
      surrounding the circumstances at the hospital may be explainable if this
      postulated metabolic pathway took place at the time of the emergency room
      incident. Although dimethyl sulfate was not detected in any analyses pertinent to
      this event, there are plausible scientific explanations to account for that fact.
      The sulfate anion, a hydrolysis product of dimethyl sulfate, was measured at an
      appreciably elevated concentration in Ramirez' blood. The descriptions of the
      symptoms of the hospital-staff victims appear quite consistent with dimethyl
      sulfate exposures. This paper attempts to make some sense of the reported data
      and eyewitness accounts, and perhaps provide new insight for any future research
      that could further explain this reported occurrence of toxic exposure.

PMID- 9248042
TI  - Moclobemide fatalities: report of two cases and analytical determinations by GC
      MS and HPLC-PDA after solid-phase extraction.
AB  - We have described a rapid and simple solid-phase extraction on C18 cartridges of
      moclobemide suitable for the analysis of post-mortem whole blood and urine. The
      methods used for identification were GC-MS and HPLC-PDA. Quantification was
      performed by the HPLC-PDA technique with detection at 238 nm. The limit of
      detection was 0.012 microgram/ml in blood. A between-day precision study gave
      relative standard deviations which were always less than 4.7% over the entire
      range of calibration (0.2 to 20.0 micrograms/ml). The method was applied in a
      case of moclobemide overdose due to a deliberate ingestion of 4.5 g of the drug.
      A second case concerned a polyintoxication including moclobemide as one of the
      main toxins. The post-mortem whole blood concentrations were 15.5 and 13.8
      micrograms/ml respectively. Determination of the drug in other biological
      specimens is also reported.

PMID- 9248043
TI  - Molecular cloning and characterization of Drosophila ornithine aminotransferase
      gene.
AB  - The cDNA encoding the Drosophila ananassae ornithine aminotransferase (OAT, EC
      2.6.1.13) precursor has been cloned and characterized. The predicted OAT protein
      sequence is 433 amino acids long with a molecular mass of 47,352 Da and is highly
      homologous to a mammalian OAT, which is a mitochondrial matrix enzyme and is
      matured by processing of its amino terminal presequence peptide. The Drosophila
      OAT has characteristics of leader peptides present in mitochondrial proteins.
      Immunoblotting experiments using polyclonal antibodies against the partial
      sequence of the OAT protein revealed that the OAT monomer has a molecular mass of
      44 kDa. These results suggest that the Drosophila OAT is also processed and
      localized in the mitochondria. Quantitation of the OAT mRNA and measurement of
      the OAT activity during fly development show that OAT is expressed at high levels
      in the fat body of the third instar larvae in both D. ananassae and D.
      melanogaster.

PMID- 9248044
TI  - Genetic variation in the expression of the six hsp genes in the presence of heat
      shock in Drosophila melanogaster.
AB  - Genetic variation in total mRNA level of the six hsp genes (hsp22, hsp23, hsp26,
      hsp27, hsp70 and hsp82) in the presence of heat shock was investigated by using
      seventy-four second- and seventy third-chromosome lines of Drosophila
      melanogaster which have the same genetic background derived from a highly inbred
      stock. There was significant variation in all the six hsp genes for both the
      second- and third-chromosome lines except for the hsp22 gene of the third
      chromosome lines. Although all the structural genes of the heat shock proteins
      are localized on the third chromosome, the estimates of genetic variance for the
      second-chromosome lines were larger than those for the third-chromosome lines.
      Highly significant correlations between total mRNA level of the different hsp
      genes in all the combinations of the six hsp genes using the second-chromosome
      lines were found, but some of correlations for the third-chromosome lines were
      not significant. These results suggest that some second chromosome variants have
      similar effects on the expression of the different genes.

PMID- 9248045
TI  - Phylogenetic relationship of the genus Oncorhynchus species inferred from nuclear
      and mitochondrial markers.
AB  - The phylogenetic relationship among the salmonid fishes of the genus Oncorhynchus
      has been analyzed using various kinds of markers for a long time. However, there
      are three major disagreements among those studies; (1) the authenticity of the
      Pacific salmon group as a monophyletic cluster, (2) the phylogenetic relationship
      among three Pacific salmons (pink salmon, sockeye salmon, and chum salmon), and
      (3) the phylogenetic position of masu salmon. We used allozyme electrophoresis to
      clarify the phylogenetic relationship between the Pacific salmon group and the
      Pacific trout group. Furthermore, we reanalysed published mitochondrial DNA D
      loop sequences (Shedlock et al., 1992). Allozymic data and mtDNA data indicated
      the following consistent results; (1) all Pacific salmons formed a monophyletic
      cluster, (2) chum salmon and pink salmon were clustered within those Pacific
      salmons, (3) masu salmon formed a cluster with other Pacific salmons and diverged
      first in this group.

PMID- 9248046
TI  - Identification of the sex of Oriental white stork, Ciconia boyciana, by the
      polymerase chain reaction based on its sex chromosome-specific DNA sequences.
AB  - Southern blotting of HindIII-digested genomic DNAs from the female and male
      Oriental white stork (Ciconia boyciana) with the EE0.6 probe cloned from the W
      chromosome of chicken (Gallus domesticus) produced a 3.0-kb W chromosome-derived
      band specific to the female and a 3.5-kb Z chromosome-derived band common to both
      sexes. These two genomic fragments were cloned and the counterpart sequences to
      that of EE0.6 in these fragments, XH0.6 and XH0.6RSM (XH0.6-related sequence in
      the male), respectively, were subcloned. Nucleotide sequences of XH0.6 and
      XH0.6RSM showed 92% identity. PCR using a set of primer sequences from XH0.6,
      which differed several nucleotides from those in XH0.6RSM, amplified an about 300
      bp genomic sequence only from the female C. boyciana. This method was applied
      successfully to identify the sex of individual young birds of C. boyciana, an
      endangered special natural monument in Japan and whose sexes are unidentifiable
      from their external morphology.

PMID- 9248047
TI  - Looking for truth in all the wrong places? Asymmetric search of individuating
      information about stereotyped group members.
AB  - Two experiments examined how category-based expectancies (CBEs) influence
      individuating information sought when trying to make accurate judgments about the
      attitudes of targets who were members of social categories that strongly or
      weakly implied the judged attitude. CBEs produced marked asymmetries in the
      number and content of participants' questions. Specifically, participants
      addressed fewer questions to stereotyped targets (STs) than to nonstereotyped
      targets (NSTs), thus acquiring relatively little individuating information about
      STs prior to judgement. Questions asked STs were diagnostically asymmetric-a
      response could better confirm than disconfirm the expected attitude, but
      questions to NSTs were diagnostically symmetric-a response could equally confirm
      or disconfirm the attitude. The authors discuss asymmetric search as a mechanism
      that may protect CBEs against disconfirmation independent of biased processing of
      acquired information.

PMID- 9248048
TI  - Simultaneous assimilation and contrast effects in judgments of self and others.
AB  - Judgments of self and referent others tend to be positively related, as evident
      in the false consensus effect, but others may also be contrasted from the self,
      as noted in the false uniqueness literature. In 3 studies that examined the
      domains of attitudes and traits, evidence of both assimilative and contrastive
      associations between self- and other-judgements were noted, depending on the form
      of judgment (objective vs. subjective) and the relevant judgment scale anchor
      (self vs. others). When self-judgments were made first, objective appraisals of
      reference groups were contrasted from subjective self-appraisals (after
      controlling for individual differences in participants' behavioral reports). When
      judgments of others were made first, objective self-ratings were contrasted from
      subjective other-judgments. Implications for the false consensus literature and
      the shifting standards model (M. Biernat, M. Manis, & T. E. Nelson, 1991) are
      discussed.

PMID- 9248049
TI  - Effects of communication, information overlap, and behavioral consistency on
      consensus in social perception.
AB  - Three experiments (N = 69, 162, and 201, respectively) were conducted to test the
      mathematically derived predictions of the Weighted Average Model (D. A. Kenny,
      1991) of consensus in interpersonal perception. Study 1 estimated the effect of
      perceiver communication. Study 2 estimated the effects of communication and
      stimulus overlap, and Study 3 estimated the effects of communication, overlap,
      and target consistency on consensus. The strongest consensus was found when
      perceivers communicated about highly overlapping information about targets who
      were cross-situationally consistent. Conversely, the lowest level of consensus
      was observed when perceivers did not communicate and had nonoverlapping
      information about targets who were cross-situationally inconsistent. Both
      stimulus variables (overlap and consistency) and an interpersonal variable
      (communication) affected consensus as predicted by the Weighted Average Model.

PMID- 9248050
TI  - Failure to recognize the effect of implicit social influence on the presentation
      of self.
AB  - Two studies demonstrated that individuals can fail to detect changes in their
      actions that are induced by implicit social influence. In both studies,
      observers' impressions indicated that actors matched the positivity of their
      remarks about themselves to the positivity of another person's self-description.
      However, actors' own judgments of the types of impressions they conveyed revealed
      that they did not perceive the effect of the other's self-description on their
      self-presentation. Study 1 suggested that actors' relatively poor access to their
      own nonverbal behavior could not fully account for their failure to perceive how
      they were influenced. Study 2 indicated that actors' metaperceptions were
      connected to actors' general beliefs about themselves, whereas observers'
      impressions were not. The "blindness" effect was driven primarily by actors low
      in self-esteem. Implications for self-presentation and other social phenomena are
      discussed.

PMID- 9248051
TI  - When self-categorization makes sense: the role of meaningful social
      categorization in minority and majority members' self-perception.
AB  - The authors examined the joint influence of meaningful social categorization and
      relative in-group size on the depersonalization of self-perception.
      Meaningfulness of social categorization was varied following the fit principle,
      introduced by self-categorization theory. In Experiment 1, the authors predicted
      and found that minority members show more depersonalized self-perception than
      majority members if, and only if, the meaningfulness of the underlying in-group
      out-group categorization is high as opposed to low. Experiment 2 further
      substantiated that a meaningful social categorization affects only minority
      members' self-perception. Finally, the conceptual relationship between fit,
      meaning, and identity is discussed.

PMID- 9248052
TI  - Interpersonal forgiving in close relationships.
AB  - Forgiving is a motivational transformation that inclines people to inhibit
      relationship-destructive responses and to behave constructively toward someone
      who has behaved destructively toward them. The authors describe a model of
      forgiveness based on the hypothesis that people forgive others to the extent that
      they experience empathy for them. Two studies investigated the empathy model of
      forgiveness. In Study 1, the authors developed measures of empathy and
      forgiveness. The authors found evidence consistent with the hypotheses that (a)
      the relationship between receiving an apology from and forgiving one's offender
      is a function of increased empathy for the offender and (b) that forgiving is
      uniquely related to conciliatory behavior and avoidance behavior toward the
      offending partner. In Study 2, the authors conducted an intervention in which
      empathy was manipulated to examine the empathy-forgiving relationship more
      closely. Results generally supported the conceptualization of forgiving as a
      motivational phenomenon and the empathy-forgiving link.

PMID- 9248053
TI  - Sensory-processing sensitivity and its relation to introversion and emotionality.
AB  - Over a series of 7 studies that used diverse samples and measures, this research
      identified a unidimensional core variable of high sensory-processing sensitivity
      and demonstrated its partial independence from social introversion and
      emotionality, variables with which it had been confused or subsumed in most
      previous theorizing by personality researchers. Additional findings were that
      there appear to be 2 distinct clusters of highly sensitive individuals (a smaller
      group with an unhappy childhood and related variables, and a larger group similar
      to nonhighly sensitive individuals except for their sensitivity) and that
      sensitivity moderates, at least for men; the relation of parental environment to
      reporting having had an unhappy childhood. This research also demonstrated
      adequate reliability and content, convergent, and discriminant validity for a 27
      item Highly Sensitive Person Scale.

PMID- 9248054
TI  - Fear of death and the judgment of social transgressions: a multidimensional test
      of terror management theory.
AB  - The purpose of the research was to integrate a multidimensional approach to fear
      of personal death with terror management theory. In Study 1, 190 students were
      divided according to the manipulation of death salience and the intrapersonal and
      interpersonal aspects of fear of death and were asked to judge transgressions
      that have either intrapersonal or interpersonal consequences. Study 2 was a
      conceptual replication of Study 1, with the exception that the manipulation of
      mortality salience included conditions that made salient either intrapersonal or
      interpersonal aspects of death. Findings indicate that the effects of mortality
      salience depend on the aspect of death that is made salient, the aspect of death
      that individuals most fear, and the type of the judged transgression. More severe
      judgments of transgressions after death salience manipulation were found mainly
      when there was a fit between these 3 factors. Findings are discussed in light of
      terror management theory.

PMID- 9248055
TI  - Parental divorce: effects on individual behavior and longevity.
AB  - Using an archival prospective design, the authors studied associations among
      parental divorce occurring during participants' childhood, adult psychosocial
      mediators, and mortality over the life span of a subgroup of participants (N =
      1,261) in the Terman Life Cycle Study (1921-1991). Children from divorced
      families grew up to show a higher risk of premature mortality across the life
      span. The higher mortality risk for men was explained, in part, when 3 mediating
      factors were controlled: Men who had experienced parental divorce were more
      likely to have their own marriages end in divorce, obtained less education, and
      engaged in fewer service activities. Women who had experienced parental divorce
      smoked more and were more likely themselves to divorce, both of which predicted
      higher mortality risk. The findings extend previous work on the negative sequelae
      of parental divorce to long-term effects on personality and longevity.

PMID- 9248056
TI  - The self as a mediator between personality and adjustment.
AB  - The self can be conceptualized as a mediating agent that translates personality
      into situated goal-directed activities and adaptation. This research used a level
      of-analysis approach to link personality dimensions (Level I) to self-systems
      (Level II) and to teacher ratings of adjustment in African American, Mexican
      American, and European American students (N = 317). The authors hypothesized that
      links among aspects of self-esteem and teacher ratings of adjustment would be
      domain specific, and those links to dimensions of the 5-factor model would
      reflects the domain specificity. Structural equation modeling corroborated
      hypotheses about domain specificity in links between adjustment and 5-factor
      dimensions. Results were discussed in terms of levels of analysis for personality
      structure, personality development, and age-related adaptations to social
      contexts.

PMID- 9248057
TI  - Ability analysis of gender relevance and sex differences in cardiovascular
      response to behavioral challenge.
AB  - Cardiovascular effects of gender-specific ability perceptions (ability
      perceptions linked to one's identity as being female or male) were examined under
      different task conditions. In Study I, participants were led to believe that
      either men (masculine task) or women (feminine task) tend to do well on a memory
      task and then were provided the chance to avoid noise by attaining a low or high
      performance standard. As expected, sex differences in systolic blood pressure
      response during performance depended not only on task type but also on the degree
      of challenge. In Study 2, high standard effects were strengthened and extended
      through the use of an appetitive procedure and the inclusion of conditions in
      which the performance standard was extreme. Findings are discussed in terms of an
      interactional analysis of ability percepts, task demand, and cardiovascular
      responsivity.

PMID- 9248058
TI  - Partners' stress underestimations lead to women's distress: a study of pregnant
      inner-city women.
AB  - The authors examined how men's underestimation of the stress that their pregnant
      female partners reported influenced women's psychological distress and their
      sense that they were not supported. Participants included 68 pregnant inner-city
      women and their partners, among whom African Americans and European Americans
      were represented. Women who reported a greater number of stressful life events
      had increased depression if their partners did not report them as encountering
      these events. However, if their partners reported them as encountering a high
      number of stressful events, the otherwise negative impact of stress was buffered.
      Partners' stress report had no appreciable effect when women reported a low
      number of stressful events. This partner underestimation effect was independent
      of the influence of women's report of social support.

PMID- 9248059
TI  - Fine-scale processing in human binocular stereopsis.
AB  - Many studies have demonstrated that the human visual system is sensitive to very
      small differences in relative binocular disparity. It is not known over what
      monocular regions information is spatially integrated to mediate performance in
      such tasks. In this study we present psychophysical observations that define the
      smallest spatial scale involved in disparity processing, and we indicate the
      nature of the computations performed by the units mediating that disparity
      discrimination. We show that human observers can identify the sign of disparity
      of a single target dot when it is embedded in a row of identical dots, with these
      noise dots presented either in the fixation plane or with a proportion
      binocularly uncorrelated. In conjunction with the psychophysical data, we explore
      how a class of simple correlator models of stereopsis must be constrained in
      order to account for human performance for the same fine-scale tasks. Such models
      can perform the task only when the correlation is carried out over a very small
      region of the image, for a very small range of disparities. Our results
      demonstrate that there is a fine-scale input to the stereo system, mediated by
      foveal mechanisms that spatially integrate visual signals over a region as small
      as 4-6 arcmin in diameter.

PMID- 9248060
TI  - Anatomically accurate, finite model eye for optical modeling.
AB  - There is a need for a schematic eye that models vision accurately under various
      conditions such as refractive surgical procedures, contact lens and spectacle
      wear, and near vision. Here we propose a new model eye close to anatomical,
      biometric, and optical realities. This is a finite model with four aspheric
      refracting surfaces and a gradient-index lens. It has an equivalent power of
      60.35 D and an axial length of 23.95 mm. The new model eye provides spherical
      aberration values within the limits of empirical results and predicts chromatic
      aberration for wavelengths between 380 and 750 nm. It provides a model for
      calculating optical transfer functions and predicting optical performance of the
      eye.

PMID- 9248061
TI  - The NEURON simulation environment.
AB  - The moment-to-moment processing of information by the nervous system involves the
      propagation and interaction of electrical and chemical signals that are
      distributed in space and time. Biologically realistic modeling is needed to test
      hypotheses about the mechanisms that govern these signals and how nervous system
      function emerges from the operation of these mechanisms. The NEURON simulation
      program provides a powerful and flexible environment for implementing such models
      of individual neurons and small networks of neurons. It is particularly useful
      when membrane potential is nonuniform and membrane currents are complex. We
      present the basic ideas that would help informed users make the most efficient
      use of NEURON.

PMID- 9248062
TI  - Multiunit normalized cross correlation differs from the average single-unit
      normalized correlation.
AB  - As the technology for simultaneously recording from many brain locations becomes
      more available, more and more laboratories are measuring the cross-correlation
      between single-neuron spike trains, and between composite spike trains derived
      from several undiscriminated cells recorded on a single electrode (multiunit
      clusters). The relationship between single-unit correlations and multiunit
      cluster correlations has not yet been fully explored. We calculated the
      normalized cross-correlation (NCC) between single-unit spike trains and between
      small clusters of units recorded in the rat somatosensory cortex. The NCC between
      small clusters of units was larger than the NCC between single units. To
      understand this result, we investigated the scaling of the NCC with the number of
      units in a cluster. Multiunit cross-correlation can be a more sensitive detector
      of neuronal relationship than single-unit cross-correlation. However, changes in
      multiunit cross-correlation are difficult to interpret uniquely because they
      depend on the number of cells recorded on each electrode and because they can
      arise from changes in the correlation between cells recorded on a single
      electrode or from changes in the correlation between cells recorded on two
      electrodes.

PMID- 9248063
TI  - A simple common contexts explanation for the development of abstract letter
      identities.
AB  - Abstract letter identities (ALIs) are an early representation in visual word
      recognition that are specific to written language. They do not reflect visual or
      phonological features, but rather encode the identities of letters independent of
      case, font, sound, and so forth. How could the visual system come to develop such
      a representation? We propose that because many letters look similar regardless of
      case, font, and other characteristics, these provide common contexts for visually
      dissimilar uppercase and lowercase forms of other letters (e.g., e between k and
      y in key and E in the visually similar context K-Y). Assuming that the
      distribution of words' relative frequencies is comparable in upper- and lowercase
      (that just as key is more frequent than pew, KEY is more frequent than PEW),
      these common contexts will also be similarly distributed in the two cases. We
      show how this statistical regularity could lead Hebbian learning to produce ALIs
      in a competitive architecture. We present a self-organizing artificial neural
      network that illustrates this idea and produces ALIs when presented with the most
      frequent words from a beginning reading corpus, as well as with artificial input.

PMID- 9248065
TI  - Indicators of the sustainability of heavy-metal management in agro-ecosystems.
AB  - The aim of sustainable heavy-metal management in agro-ecosystems is to ensure
      that the soil continues to fulfil its function in agricultural production, in
      environmental processes such as the cycling of elements, and as a habitat of
      numerous organisms. Assessment of sustainability has to be carried out in time,
      since metal accumulation in soil is largely irreversible and may cause problems
      if certain concentration levels are exceeded. In this study, we provide a concept
      to assess the sustainability of current metal cycles in agro-ecosystems based on
      dynamic heavy-metal balances for the plough layer. After presenting some general
      aspects of dynamic metal balances, we introduce 'sustainability indices'. These
      characteristic numbers can be used as indicators for potentially adverse effects
      of current agricultural practices, since they account for (ecotoxicologically
      founded) soil quality standards and for quality standards for produce,
      groundwater and surface water. They can also be used to assess the effects of
      different management options that aim to prevent quality standards from being
      exceeded as they provide insight in the dynamics governing input-output
      relationships. This is illustrated with a case study on heavy-metal flows in
      different arable farming systems.

PMID- 9248064
TI  - Effect of voice quality on perceived height of English vowels.
AB  - Across a variety of languages, phonation type and vocal-tract shape
      systematically covary in vowel production. Breathy phonation tends to accompany
      vowels produced with a raised tongue body and/or advanced tongue root. A
      potential explanation for this regularity, based on a hypothesized interaction
      between the acoustic effects of vocal-tract shape and phonation type, is
      evaluated. It is suggested that increased spectral tilt and first-harmonic
      amplitude resulting from breathy phonation interact with the lower-frequency
      first formant resulting from a raised tongue body to produce a perceptually
      'higher' vowel. To test this hypothesis, breathy and modal versions of vowel
      series modelled after male and female productions of English vowel pairs /i/ and
      /i/, /u/ and /[symbol: see text]/, and /lamda/ and /a/ were synthesized. Results
      indicate that for most cases, breathy voice quality led to more tokens being
      identified as the higher vowel (i.e. /i/, /u/, /lamda/). In addition, the effect
      of voice quality is greater for vowels modelled after female productions. These
      results are consistent with a hypothesized perceptual explanation for the
      covariation of phonation type and tongue-root advancement in West African
      languages. The findings may also be relevant to gender differences in phonation
      type.

PMID- 9248066
TI  - Evaluation of sugar cane hemicellulose hydrolyzate for cultivation of yeasts and
      filamentous fungi.
AB  - Sugar cane bagasse hemicellulosic fraction submitted to hydrolytic treatment with
      100 mg of sulfuric acid per gram of dry mass, at 140 degrees C for 20 min, was
      employed as a substrate for microbial protein production. Among the 22 species of
      microorganisms evaluated, Candida tropicalis IZ 1824 showed TRS consumption rate
      of 89.8%, net cell mass of 11.8 g L-1 and yield coefficient (Yx/s) of 0.50 g g-1.
      The hydrolyzate supplemented with rice bran (20.0 g L-1), P2O5 (2.0 g L-1) and
      urea (2.0 g L-1) provided a TRS consumption rate of 86.3% and a cell mass of 8.4
      g L-1. At pH 4.0 cellular metabolism was inhibited, whereas at pH 6.0 the highest
      yield was obtained. The presence of furfural (2.0 g L-1) hydroxymethylfurfural
      (0.08 g L-1) and acetic acid (3.7 g L-1) in the hydrolyzate did not interfere
      with cultivation at pH 6.0.

PMID- 9248067
TI  - Fiber-reinforced polymeric composites are susceptible to microbial degradation.
AB  - A mixed culture of fungi, enriched from degraded polymeric materials, formed
      biofilms on coupons of fiber-reinforced polymeric composites (FRPCs). They grew
      actively in aqueous extracts of the composites under ambient conditions. The data
      indicate that the fungi utilized the resins or fiber chemical sizing as carbon
      and energy sources. A progressive decline in impedance from above 10(7) Ohms to
      below 10(8) Ohms was detected in the inoculated FRPC panels by electrochemical
      impedance spectroscopy (EIS) after 179 days of incubation, but not on the sterile
      controls. The degradation proceeds through an initial ingress of water into the
      resins, followed by degradation of bonding between fiber surfaces and resins and
      finally separation of fibers from the resins. At the end of EIS study, the extent
      of disbonding in the inoculated composite was greater than the control observed
      by scanning electron microscopy. These results suggest that the composite
      materials are susceptible to microbial attack by providing nutrients for growth.

PMID- 9248068
TI  - Derepressed utilization of L-malic acid and succinic acid by mutants of
      Pachysolen tannophilus.
AB  - Utilization of the tricarboxylic acid (TCA) cycle intermediates, L-malic acid and
      succinic acid, by the yeast Pachysolen tannophilus is repressed in the presence
      of glucose. Strains of P. tannophilus containing mutations in two hexokinases and
      a glucokinase were characterized for growth on glucose plus L-malic acid or
      succinic acid. Increased specific utilization rates of malic acid and succinic
      acid in the presence of glucose were observed in mutants containing a lesion in
      hexokinase A, an enzyme associated with catabolite repression. Such derepressed
      mutants may have application in winemaking in which utilization of a major grape
      acid, L-malic acid, is often desirable for acidity reduction.

PMID- 9248069
TI  - Importance of biofilm formation for corrosion inhibition of SAE 1018 steel by
      axenic aerobic biofilms.
AB  - To investigate if corrosion inhibition by aerobic biofilms is a general
      phenomenon, carbon steel (SAE 1018) coupons were exposed to a complex liquid
      medium (Luria-Bertani) and seawater-mimicking medium (VNSS) containing fifteen
      different pure-culture bacterial suspensions representing seven genera. Compared
      to sterile controls, the mass loss in the presence of these bacteria (which are
      capable of developing a biofilm to various degrees) decreased by 2- to 15-fold.
      The extent of corrosion inhibition in LB medium depended on the nature of the
      biofilm: an increased proportion of live cells, observed with confocal scanning
      laser microscopy (CSLM) and image analysis, decreased corrosion. Corrosion
      inhibition in LB medium was greatest with Pseudomonas putida (good biofilm
      formation), while metal coupons exposed to Streptomyces lividans in LB medium
      (poor biofilm formation) corroded in a manner similar to the sterile controls.
      Pseudomonas mendocina KR1 reduced corrosion the most in VNSS. It appears that
      only a small layer of active, respiring cells is required to inhibit corrosion,
      and the corrosion inhibition observed is due to the attached biofilm.

PMID- 9248070
TI  - Physiological stress in batch cultures of Pseudomonas putida 54G during toluene
      degradation.
AB  - Physiological stress associated with toluene exposure in batch cultures of
      Pseudomonas putida 54G was investigated. P. putida 54G cells were grown using a
      continuous vapor phase feed stream containing 150 ppmv or 750 ppmv toluene as the
      sole carbon and energy source. Cells were enumerated on non-selective (R2A agar
      plates) and a selective minimal medium incubated in the presence of vapor phase
      toluene (HCMM2). Differential recovery on the two media was used to evaluate
      bacterial stress, culturability and loss of toluene-degrading capability. A
      majority of the bacteria were reversibly stressed and could resume active colony
      formation on selective medium after passage on non-selective medium. A small
      fraction of the bacterial cells suffered an irreversible loss of toluene
      degradation capability and were designated as Tol- variants. Numbers of stressed
      organisms increased with duration of toluene exposure and toluene concentration
      and coincided with accumulation of metabolic intermediates from incomplete
      toluene degradation. Respiring cell numbers in the batch cultures decreased as
      injury increased, indicating a possible relationship between respiring and
      injured cells. Rate expressions for injury, for formation of Tol- variants and
      for growth of Tol- variants were determined by calibrating a theoretical model to
      the results obtained. These rate expressions can be used to calibrate bioreactor
      models, and provide a basis for better design and control of bioremediation
      systems.

PMID- 9248071
TI  - Factors regulating production of alpha-galactosidase from Bacillus sp. JF2.
AB  - Certain factors affecting the production of cell-associated alpha-galactosidase
      by Bacillus sp. JF2 were investigated. The intention was to maximize alpha
      galactosidase activity of potential commercial application, by consecutive
      optimization of growth media and conditions. The highest alpha-galactosidase
      activity was obtained when grown on melibiose, whereas sucrose inhibited the
      production of alpha-galactosidase, alpha-Galactosidase production was optimally
      active at pH 7.5 and 55 degrees C. It was identified that a soy effluent stream
      could be used as the best carbon source for alpha-galactosidase by Bacillus sp.
      JF2.

PMID- 9248072
TI  - Isolation and characterization of two plasmids from Bifidobacterium longum.
AB  - In order to develop a cloning vector system which can be used in Bifidobacterium
      sp., we screened about 100 bifidobacteria from the faeces of adults and children.
      Among them, only one strain, identified as B. longum KJ, was shown to contain
      extrachromosomal DNAs. Bifidobacterium longum KJ showed multiple plasmid DNA
      bands which were resolved to be multimers of two plasmids designated pKJ36 and
      pKJ50. These plasmids were cloned into the Escherichia coli vector pUC19 as pMS36
      and pMS50, respectively, and restriction-mapped.

PMID- 9248073
TI  - Use of RAPD and 16S rDNA sequencing for the study of Lactobacillus population
      dynamics in natural whey culture.
AB  - The development of communities of the thermophilic microflora of natural whey
      culture for Parmigiano Reggiano cheese production was studied by means of
      molecular techniques. RAPD analysis facilitates the identification of the
      Lactobacillus strains involved in this microbial association and permitted the
      study of population dynamics during two cycles of whey fermentation. Analysis of
      RAPD fingerprints revealed the presence of four biotypes that dominate the whey
      fermentation process. Sequence analysis of 16S rDNA demonstrated that the strains
      isolated from whey belong to Lact. helveticus and Lact. delbrueckii ssp. lactis
      species.

PMID- 9248074
TI  - Repetitive element PCR fingerprinting (rep-PCR) using enterobacterial repetitive
      intergenic consensus (ERIC) primers is not necessarily directed at ERIC elements.
AB  - We examined the use of enterobacterial repetitive intergenic consensus (ERIC)
      sequences in PCR on the DNAs of various bacteria, bacteriophage, invertebrates,
      fungi, plants and vertebrates and have shown that complex ERIC-PCR patterns can
      be readily produced from all of these target organisms. A range of annealing
      temperatures was tested, from 52 degrees C (the commonly used annealing
      temperature) to 66 degrees C (the approximate Tm of ERIC primers). At the higher
      temperatures, most bands failed to amplify, the exception being a subset of bands
      from enterobacterial targets. It was concluded that ERIC-PCR does not necessarily
      direct amplification from genuine ERIC sequences.

PMID- 9248075
TI  - Preliminary studies on tannin degradation by Aspergillus niger van Tieghem MTCC
      2425.
AB  - A tannin-degrading strain of Aspergillus niger van Tieghem was grown at pH 5.0
      and 30 degrees C in a defined medium where tannins were the sole source of carbon
      and energy. The fungus had variable growth in tannic acid- and quebracho tannin
      medium and could tolerate these tannins even up to 150 g-1 without showing any
      growth inhibition.

PMID- 9248076
TI  - Production and detection of muramidase and acetylglucosaminidase from Agaricus
      bisporus.
AB  - The production and regulation of extracellular bacteriolytic enzymes of Agaricus
      bisporus are being studied to understand better the nutrition of this fungus and
      to identify factors that regulate the selectivity of mushroom compost as a growth
      medium. Both muramidase (EC.3.2.1.17) and N-acetyl-beta-D-glucosaminidase (beta
      GlcNAcase, EC.3.2.1.30) have been detected in liquid cultures of A. bisporus, and
      in cultures fruiting in sterile and non-sterile compost. A turbidometric assay,
      based on the decrease in optical density of suspended Bacillus subtilis bacterial
      cell walls, was used to measure muramidase production by A. bisporus. A
      colorimetric assay was used to measure beta-GlcNAcase. Both bacteriolytic enzyme
      activities were produced on a range of sole carbon sources, including killed
      freeze-dried B. subtilis cells. Muramidase activity was highest in axenic compost
      cultures. Bacteriolytic enzyme activity peaked as the first group of fruit bodies
      was harvested in both sterile and non-sterile compost.

PMID- 9248077
TI  - Direct extraction of microbial community DNA from humified upland soils.
AB  - This paper describes a protocol effective at extracting high yields of high
      purity microbial community DNA from humified soils. DNA was extracted from soil
      by lysozyme, SDS and freeze-thaw lysis, precipitated and then subjected to a
      double caesium chloride density gradient centrifugation stage before
      concentrating and washing. Evaluation using three soils yielded up to 30
      micrograms DNA g-1 dry soil, with absorbance ratios at 260:230 nm and 260:280 nm
      of 1.6-2.0. The DNA extracted from the three soils was digested by four
      restriction enzymes and a 16S rDNA eubacterial product was amplified by PCR.
      These tests indicated that the DNA obtained by the protocol was sufficiently pure
      for molecular biological analysis.

PMID- 9248078
TI  - Passive immunization of the tiger prawn, Penaeus monodon, using rabbit antisera
      to Vibrio harveyi.
AB  - Passive immunization, toxicity neutralization and the persistence of passive
      protection in the tiger prawn (Penaeus monodon) were investigated using rabbit
      antisera to the formalinized extracellular products (ECP) (R alpha ECP) and/or
      formalinized bacterial cells (R alpha BC) of luminescent Vibrio harveyi strain
      820514 originally isolated from diseased tiger prawns. Rabbit antiserum to bovine
      serum albumin (R alpha BSA) or phosphate-buffered saline (PBS, pH 7.2) both
      served as controls. The toxicity of ECP to prawns was neutralized by pre
      incubation with R alpha ECP. Passive immunization by pre-injection of R alpha BC
      or R alpha ECP into prawns 3 d in advance protected against a lethal dose
      challenge of bacteria. To determine the persistence of passive protection by
      rabbit antiserum in tiger prawns, the R alpha BC, R alpha ECP, R alpha BSA or PBS
      were injected into prawns. At 10, 17 or 24 d post-immunization, groups of prawns
      were given a lethal dose challenge of bacteria. The prawns in the two control
      groups were all killed within the first 2 d following challenge at all three
      challenge dates. Pre-injection with R alpha BC and R alpha ECP provided total
      protection for 10 and 17 d, respectively, with all treated prawns surviving for
      at least 2 weeks post-challenge. This is the first study using mammalian antisera
      to investigate toxicity neutralization, passive immunization and persistence of
      passive protection by rabbit antisera in prawns. The results could be useful in
      future studies on virulence mechanisms and disease control of vibriosis in
      cultured prawns.

PMID- 9248079
TI  - In vitro cariogenicity of trans-galactosyl-oligosaccharides.
AB  - Trans-galactosyl-oligosaccharides (TOS) are a class of oligosaccharides produced
      by transgalactosylation of lactose. TOS are used as bifidogenic factors in human
      and animal nutrition. TOS can be present in the oral cavity and form a risk of
      caries. All oral bacteria tested were able to degrade and ferment both TOS and
      galactosyllactose (GLL), one of its components. Growth was improved compared with
      carbohydrate-free media and acid was produced after 24 h incubation of the
      bacteria with TOS and GLL. Degradation patterns, using HPAEC, showed degradation
      of most components. GLL was degraded only partially. Rapid acidification was only
      observed for Streptococcus mutans, resulting in a pH of 5.4 within 30 min. All
      other strains fermented TOS and GLL only slowly. Plaque formation could not be
      detected on both substrates. It can be concluded that TOS and GLL present only a
      small risk of caries formation, unless proven otherwise in animal studies.

PMID- 9248080
TI  - Barotolerance is dependent on both trehalose and heat shock protein 104 but is
      essentially different from thermotolerance in Saccharomyces cerevisiae.
AB  - The contribution of trehalose and hsp104 to barotolerance in Saccharomyces
      cerevisiae has been investigated. Mutant strains, which lacked the ability to
      accumulate trehalose and/or hsp104, were examined for barotolerance and
      thermotolerance. All the mutants showed lower barotolerance and thermotolerance
      than their control strains. Trehalose had a greater protective effect towards
      high pressure than high temperature. Thus, trehalose and hsp104 are important
      factors for barotolerance and thermotolerance, but trehalose is more important
      for barotolerance than for thermotolerance.

PMID- 9248081
TI  - The effect of high hydrostatic pressure on the activity of intracellular enzymes
      of Listeria monocytogenes.
AB  - The effect of high hydrostatic pressure (100-550 MPa, 15 min, ambient
      temperature) on the activity of 13 metabolic enzymes produced by all three
      strains of Listeria monocytogenes (NCTC 11994, a poultry isolate and Scott A) was
      examined using gel electrophoresis. The enzymes assayed exhibited a wide
      variation in barotolerance. The pressure resistance of each particular enzyme was
      not dependent on the strain from which it was derived. This would seem to
      indicate that these enzymes were not a determining factor in relation to
      previously observed differences in the overall pressure resistance of the three
      strains.

PMID- 9248082
TI  - Subspecies differentiation of Salmonella by PCR-RFLP of the ribosomal operon
      using universal primers.
AB  - A polymerase chain reaction (PCR)-based method was developed to aid
      identification of bacteria to subspecies level. The method used primers that
      annealed to highly conserved regions of the bacterial rRNA operon, which are
      proposed to be universal for all bacteria. The resulting PCR products gave unique
      electrophoretic patterns due to restriction fragment length polymorphisms (RFLP)
      within the rRNA operon, allowing differentiation to the subspecies level. Six
      serotypes of Salmonella choleraesuis are presented to demonstrate the specificity
      of PCR-RFLP patterns for building an identification database. As the database
      continues to accumulate, the method proves to be specific and rapid for
      identifying bacteria based on stable genetic characteristics.

PMID- 9248084
TI  - Isolation of a Pseudomonas species from fish intestine that produces a protease
      active at low temperature.
AB  - A psychrotrophic bacterium producing a protease active at low temperatures was
      isolated from fish intestine and identified as a Pseudomonas species. Optimum
      growth and protease-producing temperatures of this strain were 15 degrees C and
      10 degrees C, respectively. The maximum temperature for proteolytic activity was
      25 degrees C, an unusually low temperature.

PMID- 9248083
TI  - The characterization and description of representatives of 'G' bacteria from
      activated sludge plants.
AB  - The name Tetracoccus cechii is proposed for two strains of the tetrad arranged
      cocci, previously known as 'G' bacteria, which were isolated from laboratory
      scale activated sludge plants in the Czech Republic and in Italy. They were
      morphologically, phenotypically and phylogenetically characterized and found to
      comprise a novel lineage in the alpha-3 group of the proteobacterial phylum in
      the domain Bacteria. The strains are Gram-negative and produce intracellular
      inclusions of poly-beta-hydroxybutyrate. Although commonly seen in activated
      sludge mixed liquor as cocci 1-2 microns in diameter, arranged in tetrads, in
      pure culture they can also grow in amorphous aggregations and the cells are
      generally more variable in their size and shape with coccobacilli as well as
      cocci being present. They are not able to grow phototrophically, nor can they
      reduce nitrate beyond nitrite nor grow anaerobically. The closest phylogenetic
      neighbours of T. cechii are Rhodobacter sphaeroides and R. capsulatus which are
      93% similar by 16S rDNA comparison. Tetracoccus cechii is oxidase- and catalase
      positive, non-motile and has an optimal growth temperature between 25 degrees and
      35 degrees C. The 16S rRNA of T. cechii has a 21 nucleotide deletion in the V9
      region (Escherichia coli positions 1258-1278) and this feature is a unique
      molecular synapomorphy in the alpha-3 group.

PMID- 9248085
TI  - Research note: unsuitability of the MRS medium for the screening of hydrogen
      peroxide-producing lactic acid bacteria.
AB  - The effect of MRS broth on the stability of hydrogen peroxide (H2O2) has been
      studied. Known concentrations (1-100 micrograms ml-1) of H2O2 were prepared in
      distilled water, phosphate buffer (pH 7.0) and MRS broth (pH 6.2 and 3.9). H2O2
      was very stable in aqueous and buffer solutions but it was rapidly degraded in
      MRS broth (pH 3.9). The presence of H2O2 in MRS broth (pH 6.2) could not be
      detected.

PMID- 9248086
TI  - New method for RNA isolation from actinomycetes: application to the
      transcriptional analysis of the alcohol oxidoreductase gene thcE in Rhodococcus
      and Mycobacterium.
AB  - A new protocol for the isolation of RNA from Rhodococcus and other actinomycetes
      such as Mycobacterium and Amycolatopsis was developed. The method is based on
      rapid lysis of cells in a high-speed reciprocal shaker using small abrasive
      particles followed by spin column purification of the lysate. This quick
      procedure yields RNA preparations suitable for functional studies. This was shown
      for the thcE gene of R. erythropolis NI86/21, which encodes a N,N'-dimethyl-4
      nitrosoaniline-dependent alcohol oxidoreductase. The thcE transcript was detected
      by Northern hybridization in R. erythropolis, R. fascians, Mycobacterium
      chlorophenolicum and Mycobacterium smegmatis. The transcriptional start point of
      the gene was determined by primer extension of the R. erythropolis mRNA.

PMID- 9248087
TI  - [Diagnosis of local recurrences and metastases from colorectal cancers].
AB  - The risk of relapse of colorectal cancer depends on tumor characteristics such as
      location and Dukes' stage. Recurrences may be metastatic only (70%), locoregional
      only (20%) or both (10%). The main objective of postoperative follow-up is to
      detect recurrent disease as early as possible, in order to allow curative
      resection. Most relapses are now diagnosed when still asymptomatic. Different
      imaging methods help to diagnose these recurrences. The CT scan allows to examine
      the liver, lymph nodes, anastomosis and the pelvic cavity. MRI can bring
      complementary information in some selected cases. Lastly, percutaneous needle
      biopsies will be useful to prove the diagnosis. For the detection of distant
      metastases, chest X-ray, hepatic echography and CT scan examination can be used.

PMID- 9248088
TI  - [Prognostic factors of advanced colorectal cancers].
AB  - Prognostic factors have been so far much more extensively studied for resectable
      colorectal cancers than for advanced colorectal cancers. However, the recent
      increase in treatment possibilities forces physicians to take into account the
      prognostic factors of patients with advanced colorectal cancer. The prognostic
      evaluation of these patients is still mostly based on clinical parameters, such
      as performance status and allocated treatment. More recently, the prognostic role
      of biological parameters such as p53 gene or enzymes implicated in 5-fluorouracil
      metabolisms has been identified.

PMID- 9248089
TI  - [Surgery of advanced colorectal cancers].
AB  - Tumor recurrence after "curative" resection for colorectal carcinoma is observed
      in approximately half of the patients. Careful follow up after surgery of the
      primary tumour should allow early diagnosis of the recurrence, local or
      metastatic, mostly within the liver. Reoperation for resection of the recurrence
      should be discussed, because, if possible, it can prolong survival, or even cure
      some of the patients.

PMID- 9248090
TI  - [First line chemotherapy of advanced colorectal cancers].
AB  - Nearly six patients out of ten have or will have colorectal metastasis. A first
      line chemotherapy is justified as patients' survival duration, quality of life
      and life without symptoms will be longer and as antitumor efficacy is real. Among
      classical 5-FU based intravenous chemotherapies, the 5-FU plus folinic acid
      combination should be preferred to the 5-FU plus methotrexate combination, the
      latter being difficult to survey. If continuous 5-FU infusions induce more
      responses than 5-FU bolus alone, they are similar to 5-FU bolus plus folinic
      acid, but more expensive to realise. Practically, the french chemotherapy
      protocol that we recommend in first line is a combination of bi-weekly 5-FU bolus
      plus continuous 5-FU infusion plus folinic acid, which has more efficacy and
      which is really less toxic than other 5-FU modulations. Among the new drugs
      available, raltitrexed is the only one authorized by the French government in
      first line therapy. Other therapeutic ways are possible as hepatic intra-arterial
      chemotherapy (for some special cases). The future consists of pursing trials to
      evaluate chronomodulated chemotherapy, individual adjustment of 5-FU dose, and
      new drugs.

PMID- 9248092
TI  - [Judgement criteria in treatments of advanced colorectal cancers and methods of
      evaluation].
AB  - Because of their bad prognosis, the effectiveness assessment of advanced cancer
      therapy is particularly important. A strict measurement of the treatment's
      benefit is necessary in order to consider its true interest objectively. The
      assessment of the tumor response allow an appreciation of the immediate
      effectiveness of the treatment on the lesions. An objective response doesn't mean
      that there is a survival improvement, which remains the primary aim of all
      treatments. Statistical methods are used so as to estimate overall survival or
      relapse-free arrival. Evaluating the quality of life is now essential in advanced
      cancer management. This is a complex, subjective and multi-dimensional concept
      and its evaluation requires some specific and validated instruments.

PMID- 9248091
TI  - [Chemotherapy of advanced colorectal cancers after failure of a treatment with
      fluoropyrimidine].
AB  - Second line chemotherapy is more and more frequently indicated in advanced
      colorectal cancer. Many patients are still in good general condition at the time
      of tumor progression. Several options can be discussed today, and particularly
      new drugs which have recently proved to be active in this situation. Irinotecan,
      a camptothecin derivative and specific inhibitor of the enzyme topoisomerase I
      has been approved in this indication and is able, with acceptable toxicity under
      careful monitoring, to provide a significant proportion of patients with 6 to 8
      additional months of progression-free survival. Oxaliplatin, the first clinically
      available compound of the DACH-platine family, which has specific and original
      pharmacologic and clinical properties, can also be used alone or preferably in
      combination with further fluorinated pyrimidines potentiated by folinic acid.
      Alternative schedules of fluorinated pyrimidines such as low doses continuous
      infusions of fluorouracile can finally be an option in poor prognosis patients
      since the drug has a different mechanism of action as compared to the high dose
      intermittent or modulated schedules.

PMID- 9248093
TI  - [Radiotherapy and symptomatic treatments of advanced colorectal cancers].
AB  - Treatments of colorectal cancers can still be curative up to fairly advanced
      stage. Clinical situations vary greatly depending on the primary: local
      recurrence is a major event in rectal cancer whereas metastases are the main
      problem in colon cancer. Therefore, rectal cancer benefit from locoregional
      combined treatments, chemotherapy, radiotherapy and surgery, to control the
      pelvic disease. In the metastatic setting, it is important to offer potentially
      curative treatment as often as possible. Radiotherapy for bone or brain
      metastasis is well known and frequently used; irradiation of painful liver
      metastasis is less regularly discussed despite its efficacy. Symptomatic
      treatments like analgesics narcotic or not, non steroidal anti-inflammatory,
      anxiolytics, etc. are useful. All these treatments must be evaluated, not only in
      term of anti-tumoural but also from the quality of life point of view.

PMID- 9248094
TI  - [Physiopathology of pleural diseases].
AB  - The pleura is characterized by its great capacity to drain liquids and particles
      from the pleural space and a strong inflammatory potential. Mesothelial cells
      react to various endogenous or exogenous agents, which are absent from the
      pleural space in normal conditions: air, blood, organic and inorganic particles.
      The pleura is a target organ, for specific lesions (pleural plaques,
      mesothelioma) induced by mineral fibers and for non-specific inflammatory lesions
      from multiple causes (drugs, systemic diseases, infections). The risk for
      diseases of the pleura appears disproportionate compared with its physiological
      role.

PMID- 9248095
TI  - [Diagnosis of pleurisy].
AB  - Diagnosis of pleural effusion, suggested by chest pain or dyspnea, is assessed by
      physical examination, chest X-ray sometimes completed by other imaging
      techniques, and mainly by thoracentesis. Thoracentesis is mandatory for the
      diagnostic of pleural effusion as three diagnosis are associated with an
      emergency treatment: pulmonary embolism; hemothorax; empyema. If the fluid is a
      transudate, no further invasive studies are necessary. If the cause of pleural
      exsudat cannot be established by a careful history, physical examination and
      fluid analysis, generally closed pleural biopsy should be done, followed, in
      absence of an established diagnosis, by thoracoscopy. At this time, less than 10%
      of the cases remain without explanation, leading to a careful follow-up of
      patients since a carcinomatous lesion may develop in 1/3 of them.

PMID- 9248096
TI  - [Imaging of the pleura].
AB  - We review the respective informations yielded to the physician bu the different
      techniques of medical imaging (conventional radiography, ultrasounds, and
      computed tomography) according to the presentation of pleural diseases.
      Conventional radiography is always useful for diagnosis. Ultrasound is useful to
      confirm and localize pleural effusion. Computed tomography contributes to precise
      the location of pneumothorax and pleural effusion, and the possible underlying
      pulmonary disorders. Computed tomography also allows to precisely characterize
      the different types of pleural thickening, including malignant mesothelioma.

PMID- 9248097
TI  - [Diagnostic and therapeutic thoracoscopy].
AB  - Thoracoscopy, an endoscopic examination for pleurisy, can be performed using
      general anesthesia, usually without intubation, or using a neuroleptic, after
      induction of artificial pneumothorax if required. At the end of surgery, a
      thoracic drain is inserted to expand the lung. Complications are rare and
      mortality is below 0.017%. The main indication for thoracoscopy is diagnosis of
      pleural effusion, where its sensitivity and specificity are clearly superior to
      that of needle pleural biopsy and (or) to pleural fluid cytology. In diffuse
      pulmonary diseases, thoracoscopy also allows lung biopsy. Some therapeutic
      measures are mainly feasible by this route. Pleurodesis is performed in case of
      recurrent pleural effusion of for pneumothorax.

PMID- 9248098
TI  - [Purulent pleurisy].
AB  - Management of thoracic empyema remains controversial considering local treatment
      and place of surgical intervention. If French practitioners use primarily
      iterative thoracentesis and pleural lavage, reserving thoracic drainage for cases
      of failure of thoracentesis, American authors recommend a more aggressive initial
      approach, with thoracic drainage and surgical intervention. However, conservative
      attitude, combining immediate thoracocentesis and pleural lavage with
      intrapleural fibrinolytic therapy of loculation occurs, may also be proposed.
      Prospective studies are warranted to evaluate the different methods used to
      evacuate empyema and validate new procedures as pleural catheters inserted under
      radiologic guidance and thoracoscopy versus conventional approach.

PMID- 9248099
TI  - [Spontaneous pneumothorax].
AB  - Pneumothorax corresponds to the extravasation of air in the pleural cavity. This
      produces a partial or complete collapse of the adjacent lung. This is a common
      thorax disease resulting from a leak between the broncho-pulmonary gas
      compartment and the usually virtual pleural space. Pneumothorax is called
      spontaneous when no traumatic or iatrogenic factors are present. Spontaneous
      pneumothorax can be primary (when no radiographic or clinical injuries can be
      detected) or secondary to an underlying pulmonary disorder. Evolution of
      spontaneous pneumothorax is usually benign. However, recurrence is frequent.
      Preventing recurrences is the basis of all the therapeutic controversies which,
      after drainage, are based on pleurodesia indications. Vital prognosis may be
      compromised when pneumothorax is compressive, bilateral, or when it results in
      respiratory failure in patients with chronic respiratory insufficiency.

PMID- 9248100
TI  - [Epidemiological approach to mesothelioma].
AB  - Mesothelioma, the primitive cancer of pleura, peritoneum or pericardium, is a
      tumor for which many etiologic studies have been conducted, because of close
      relations with environment. If asbestos remains the essential risk factor, many
      uncertainties persist on extent of phenomena in next decades. Furthermore,
      emergence of new etiologies, confirmed on human (erionite, ionizing radiations)
      or only suspected in experimentation (some biopersistent synthetic fibers, some
      virus as the SV40), ask new questions which are susceptible to modify our view of
      mesothelioma epidemiology.

PMID- 9248101
TI  - [Malignant mesothelioma. Diagnosis and treatment].
AB  - In over 90% of cases, mesothelioma initially presents as a banal pleural
      effusion, contributing no orientation to the diagnosis. The pleural fluid can
      even disappear after initial puncture. For early diagnosis, simple puncture, with
      or without biopsy, does not suffice. Thoracoscopy is 98% diagnostic. The course
      depends on the stage, the histological type and the general status. A new
      international TNM classification has been proposed to allow comparison of series
      and to choose a treatment appropriate to the stade: at stage I, intrapleural,
      local immuno-chemotherapy treatment gives good results; at stages II and III,
      surgery followed by radiation therapy are indicated; at stage IV, symptomatic
      treatment alone is justified.

PMID- 9248102
TI  - [HIV infection. Epidemiology, screening, prevention, main immunological
      abnormalities, prognostic biological markers, classification (evolutive
      staging)].

PMID- 9248103
TI  - [Fever on return from a tropical country. Diagnostic orientation].

PMID- 9248104
TI  - [Deep venous thrombosis of the lower limbs. Etiology, physiopathology, diagnosis,
      course, prognosis, treatment].

PMID- 9248105
TI  - [Neurological complications due to alcohol consumption. Diagnosis, treatment].

PMID- 9248106
TI  - [Turner and Klinefelter syndrome. Diagnosis].

PMID- 9248107
TI  - [Sciatica (L5 or S1). Etiology, physiopathology, diagnosis, treatment].

PMID- 9248108
TI  - Prions and prion diseases.
AB  - Currently known transmissive spongiform encephalopathies in humans and animals
      are presented. Caused by prions, they are known as "prion disease". The results
      of extensive investigations of prions are described, as well as the theories
      about their nature. Relating to the occurrence of the epizootic of bovine
      spongiform encephalopathy in England, its causes and consequences as well as the
      research on possible relationship between this encephalopathy and the Creutzfeldt
      Jakob's disease are discussed.

PMID- 9248109
TI  - Differences between male and female breast cancer. II. Clinicopathologic
      features.
AB  - The aim of this study was direct comparison of clinicopathologic features in male
      and female breast cancer patients. The study included 100 male and 500 female
      patients with pathohistologically confirmed breast cancer, who were treated at
      the University Hospital for Tumors in Zagreb, Croatia, between 1970 and 1990. The
      results revealed significant sex-related differences in the following
      characteristics: patients age at diagnosis (36% vs. 66% below the age of 60,
      respectively, p < 0.001), delay in treatment (29% vs. 58% within the first 3
      months, p < 0.001), tumor size (45% vs. 58% up to 5 cm, p < 0.001), number of
      affected regional lymph nodes (74% vs. 87% up to 5 nodes, p < 0.01), TNM-stage
      distribution (49% vs. 56% in stages I-II, p < 0.001), estrogen receptor values
      (69% vs. 32% > 10 fmol/mg protein, p < 0.001) and progesterone receptor values
      (67% vs. 48% > 10 fmol/mg protein, p < 0.05). No significant sex-related
      differences in breast cancer patients were found regarding histologic grade of
      malignancy (males: grade I-36%; II-34%; III-30%; females: grade I-33%; II-36%;
      III-31%), affected breast (left in 58% males vs. 50% females), and type of
      surgical treatment (modified radical mastectomy in 64% male vs. 61% female
      patients). This study confirmed the well-known facts that male breast cancer
      develops at an older age and with a much higher proportion of positive tumor
      hormone receptors. Furthermore, the authors found the male patients in Croatia to
      be insufficiently informed about the possibility of breast cancer development in
      male sex, which resulted in a significantly prolonged treatment delay and,
      consequently, higher TNM stage of the disease, bigger tumors and more affected
      lymph nodes at the time of diagnosis in comparison to female patients.

PMID- 9248110
TI  - Differences between male and female breast cancer. III. Prognostic features.
AB  - The aim of this study was direct comparison of prognostic features in male and
      female breast cancer patients. The study included 100 male and 500 female
      patients with pathohistologically confirmed breast cancer, who were treated at
      the University Hospital for Tumors in Zagreb, Croatia, between 1970 and 1990.
      Stage-adjusted univariate analysis of differences in five-year overall survival
      revealed similar prognosis in both sexes when the disease was in TNM-stages I and
      II (males: 95% and 80%; females: 90% and 79%, respectively). However, the study
      showed that in TNM stages III and IV, male patients had a significantly worse
      five-year overall survival (males: 39% and 5%; females: 61% and 27%,
      respectively; p < 0.05). The impact of ten clinicopathologic characteristics on
      survival in males and females was also analyzed through the multivariate
      statistical analysis, in this case by multiple regression. Analyzed
      characteristics included patient age at diagnosis, delay in treatment, tumor
      size, number of affected lymph nodes, TNM-stage, histologic grade, affected
      breast, estrogen and progesterone receptor values, and type of surgery. An
      extremely intriguing finding was that the percent of survival variance explained
      by ten selected predictors (R2) amounted to as much as 78.7% in males, in
      comparison to only 23.1% in females. Three predictors that explained most of the
      survival variance in males were TNM-stage (21.0%), number of affected lymph nodes
      (19.5%) and delay in treatment (16.2%). The most important corresponding
      prognostic factors in females were number of affected lymph nodes (12.7%),
      histologic grade (6.6%) and tumor size (5.9%). The authors concluded that, from
      the prognostic point of view, male and female breast cancer represent two quite
      different diseases: in males, the outcome can be very precisely predicted from
      the basic clinicopathologic characteristics of the disease, while in females
      there is probably a wide spectrum of other factors with a significant influence
      on the prognosis, which require additional studies.

PMID- 9248111
TI  - Psychopathological differences among three groups of school children affected by
      the war in Croatia.
AB  - The consequences of extreme violence such as war torture affect children in
      different ways and may immediately manifest at the physical and/or psychologic
      level, or may remain hidden and unrecognized for years. The victims are usually
      very reluctant to speak about their traumatic experiences, and try to deny the
      existence of psychological disturbances. They often seek help for somatic
      problems. Taking these physical complaints seriously helps to progressively reach
      the psychological effects of violence. Therefore, identification of such children
      should be directed to more complete evaluation of their symptomatology and
      functioning. This can be done by: a) individual evaluation to get enough
      information on the historical events, functioning and symptoms of these children;
      and b) standardized instruments which may allow the children to disclose more
      about their psychological experiences during the war. In this study rating scales
      and assessment instruments for children aged < 15, such as CPRS with General
      Scoring Sheet (Fish, 1985), were used to assess the broad spectrum of
      psychopathology in this age group. These questionnaires were used in a large
      group of school children (N = 1888), 989 girls and 899 boys aged 7-16 years. The
      sample was divided into 3 groups: 843 non-displaced, 377 displaced and 669
      refugee children. Results of statistical analysis (arithmetical mean and standard
      deviation of discriminative variables transformed in Z-values with F-ratio)
      showed the three groups of children (non-displaced, displaced and refugees) to
      significantly differ in 13 out of 15 psychopathologic clusters. Discriminative
      cannonic analysis of the 3 groups of children (non displaced, displaced and
      refugees) also showed significant differences. The first discriminative function
      (80.24% of total variance) indicated depression, violence and antisocial behavior
      to be rare in non-displaced children, more pronounced in displaced, and most
      pronounced in refugee children. The second discriminative function (19.76% of
      total variance) showed hyperactivity, anxiety and psychosomatic disturbances to
      be rare in non-displaced children; more frequent in refugee, and most expressed
      in displaced children. According to the results, the authors concluded that war
      is very painful for a large group of children, among whom the displaced and
      refugee children are most affected by psychopathologic disturbances.

PMID- 9248112
TI  - Histopathologic findings of placenta and arcuate artery Doppler velociometry in
      preeclampsia and intrauterine growth retardation.
AB  - The aim was to analyze the histopathologic changes of placentas and to compare
      them to the results of arcuate artery color Doppler velocimetry. Fifty four
      placentas were from pregnancies complicated with pre-eclampsia that ranged from
      mild forms to convulsions (group 1), 42 from pregnancies complicated with
      intrauterine growth retardation (IUGR) (group 2) and 40 from uncomplicated
      pregnancies (group 3). The arcuate artery resistance index (AARI) was increased
      in 66.66% in group 1 and 59.52% in group 2 (NS). In all uncomplicated pregnancies
      (group 3) AARI was normal. In group 2, increased AARI was significantly more
      frequently associated with minimal hypoxic damage (MHD) of placental tissue than
      in group 1 (p < 0.005), whereas multiple infarcts were more common in group 1
      than in group 2 (p < 0.005). At normal AARI multiple infarcts were significantly
      more frequently found in group 1 than in groups 2 and 3 (p < 0.005), whereas
      normal placental findings were significantly more common in group 3 than in
      groups 1 and 2 (p < 0.001). Hypoxic lesions were significantly more often
      associated with increased AARI (p < 0.01). The positive predictive value of
      arcuate artery color Doppler velocimetry for hypoxic placental lesions was 93%,
      and negative predictive value was 10%. Sensitivity and specificity of the method
      in the prediction of hypoxic placental lesions was 62% and 91%, respectively.

PMID- 9248113
TI  - Hydraulic optimalization of surgical flow drainage in physical model.
AB  - In the present study, the flow in deep, closed wound with various types and
      position of drain was studied. A physical model of regular geometrical wound was
      designed to investigate the events occurring in the wound from the standpoint of
      hydraulics. Results of the study showed that the commonly used method of drain
      application could be improved. The results may also prove helpful for improvement
      of the existing drains and their more favorable positioning.

PMID- 9248114
TI  - Peroxyacetic acid effect on the bacteriologic status of war wound.
AB  - In this study, the efficiency of peroxyacetic acid as a local antiseptic in war
      wound healing was investigated. Peroxyacetic acid was specially prepared for
      local application. The acidity was reduced from pH 2 to pH 5 using acetate
      buffer, the concentration was reduced to 0.2% and the use of sulfuric acid was
      avoided in the peroxyacetic acid preparation. Thirty-five patients with at least
      two similar wounds requiring daily dressing were included on a voluntary basis.
      Cranial wounds and wounds on the right side of the body were treated by
      peroxyacetic acid compresses, while other wounds were treated by the application
      of hypertonic NaCl solution. On day 12, the wounds treated by peroxyacetic acid
      (chi 2 = 52; df = 4, P < 0.001) were observed to be statistically significantly
      cleansed than the wounds treated conventionally. The use of peroxyacetic acid as
      a local antiseptic has not yet been described in the available literature. The
      possibilities and efficiency of peroxyacetic acid for this purpose, previously
      prepared for use in living tissue, are emphasized.

PMID- 9248115
TI  - Venous reflex testing in glaucoma.
AB  - The aim of this study was the assessment of physiological venous reflexes in open
      angle glaucoma. The study was carried out by a controlled clinical experiment.
      The experimental group consisted of 17 glaucoma patients with controlled
      intraocular pressure. The control group consisted of 15 healthy volunteers. The
      assessment of venous tone changes was performed by means of the test of "venous
      reflexes". Venoconstriction responses to physiological stimuli were significantly
      decreased in glaucoma patients (p < 0.05). The results suggested venous
      dysregulation as part of sympathetic dysfunction in glaucoma.

PMID- 9248116
TI  - A contribution to the etiopathogenesis of nasal polyps.
AB  - The first author studied nasal polyposis from the epidemiological, clinical,
      immunologic and histologic points of view. Based on the year-long studies, the
      authors have isolated three issue of common interest to rhinologists since
      ancient times, i.e. relationship between allergy and nasal polyposis,
      predilection sites of the origin of polyposis, and the development process
      underlying the genesis of polyps.

PMID- 9248117
TI  - Lansoprazole versus omeprazole in the treatment of reflux esophagitis.
AB  - To evaluate the therapeutic potential of the newly developed proton pump
      inhibitor lansoprazole in patients with reflux esophagitis (grade I and II
      according to Savary Muller criteria), the authors performed a single blind,
      randomized clinical trial comparing 20 mg omeprazole and 30 mg lansoprazole,
      involving 60 patients at two clinical hospitals. The treatment period was or 8
      weeks, and main efficacy variables were healing of endoscopic changes and relief
      of reflux symptoms. No significant difference in terms of healing and relief of
      reflux symptoms was found either after 4 or after 8 weeks of treatment. In
      conclusion, 30 mg lansoprazole daily was found to be safe and effective therapy
      comparable to omeprazole in the short-term treatment for reflux esophagitis
      (grade I and II).

PMID- 9248118
TI  - Autoimmune thrombocytopenia in adults: clinical experience.
AB  - Diagnostic and treatment algorithms in autoimmune thrombocytopenia (AITP) are
      still somewhat controversial. We present our experience in the diagnosis and
      treatment of 39 AITP patients, hospitalized at our department between 1990 and
      1995, and discuss alternative approaches. There were 10 male and 29 female
      patients, median age 47 (range 18-75) years. All patients had isolated
      thrombocytopenia and normal or increased number of megakaryocytes in bone marrow.
      Platelet count lower than 15 x 10(9)/L was found in 25 (64.1%) patients. Eighteen
      (54.5%) patients responded well to standard and two (6.1%) to high doses of
      steroids, whereas 18.2% of the patients responded well to other immunosuppressive
      therapy. Antiplatelet antibodies were found only in 4 (10.2%) patients. Our
      conclusion was that a half of adult AITP patients achieve satisfactory recovery
      on standard doses of steroids.

PMID- 9248120
TI  - Enterovesical fistula: 10 years experience.
AB  - BACKGROUND: Enterovesical fistula is a relatively uncommon complication of pelvic
      malignancies, diverticulitis of the colon, postoperative irradiation or trauma.
      Early diagnosis of enterovesical fistula is difficult and its management,
      complicated. The main purpose of this study is to investigate the most
      appropriate diagnostic method and to discuss the choice among different surgical
      managements. METHODS: From 1986 to 1995, 30 patients with enterovesical fistula
      were diagnosed and treated at Veterans General Hospital-Taipei. The records were
      reviewed retrospectively with regard to symptoms, primary disease process,
      diagnostic studies, management, complications, mortality and follow-up. RESULTS:
      Recurrent urinary tract infection (UTI) accounted for 73% and was the most common
      presenting symptom. Fecaluria (43%) and urine per rectum (40%) were another two
      common presenting symptoms. The major cause of these cases was malignancy (36%),
      followed by postoperative radiotherapy (17%) and iatrogenic injury (17%). Most of
      these cases were diagnosed by cystography (90%), barium enema (75%) or cystoscopy
      (69%). The rectum (52%) was the most common site involved, followed by the
      sigmoid colon (39%). The surgical management was individualized for each patient
      according to the general condition and the disease process. CONCLUSIONS: By
      combining the results of cystography, barium enema and cystoscopy, diagnosis of
      enterovesical fistula can be established in almost all cases. Single-stage
      operation for enterovesical fistula should be limited to those patients in good
      nutritional state and without severe inflammation, radiation injury, intestinal
      obstruction, other major medical problem, advanced malignancy or old age.

PMID- 9248119
TI  - Squamous cell carcinoma of esophagus with diffuse mucin-secreting component: a
      clinicopathologic study.
AB  - BACKGROUND: Primary esophageal squamous cell carcinomas with a diffuse mucin
      secreting component are not common, and the cases reported are few. The
      nomenclature for this group of tumors is complex and the histogenesis of these
      tumors is confused. Therefore, further investigation is needed. METHODS: Twelve
      cases have been collected from pathology files of Veterans General Hospital
      Taipei from 1965 to 1995. Clinicopathologic relationship, histopathological and
      immunohistochemical features of these cases were analyzed and compared with the
      reported literature concerning this entity. RESULTS: The age, sex and prognosis
      for patients of this group, and the size and site of the tumors were not
      different from that of pure squamous cell carcinoma. The tumors continuously
      connected with esophageal squamous epithelium, and intraepithelial dysplasia were
      present in 83% cases. Positive anticarcinoembryonic antigen staining was also
      demonstrated in squamous epithelium, dysplastic epithelium and tumor cells with
      either squamous or adenomatous differentiation. CONCLUSIONS: It is believed that
      esophageal squamous cell carcinoma with diffuse mucin-secreting component is
      close to the squamous cell carcinoma.

PMID- 9248121
TI  - Color Doppler ultrasound of spiral arteries in normal second-trimester
      pregnancies.
AB  - BACKGROUND: Blood flow resistance of the subplacental spiral arteries in second
      trimester pregnancies has not been previously reported. A reference range of
      blood flow resistance of the subplacental spiral arteries at 13-25 gestational
      weeks was designed in the hope the reference data could provide a basis for
      Doppler studies of pathologic disorders in second-trimester pregnancies. METHODS:
      A cross-sectional study was performed in 175 uncomplicated pregnancies at 13-25
      gestational weeks. Doppler flow examinations of the subplacental spiral arteries
      were done. RESULTS: In the 175 normal pregnancies, both the predicted
      systolic/diastolic ratios(S/ D) (Y = 1.96258-0.02061x gestational age (GA),
      adjusted R2 = 0.03773, p = 0.003) and resistance indices (RI) (Y = 0.52131
      0.00871 x GA, adjusted R2 = 0.03797, p = 0.003) of the subplacental spiral
      arteries decreased progressively with advancing gestational age. The predicted
      S/D value of the subplacental spiral artery decreased from 1.695 at the 13th
      week's gestation (5th% = 1.221, 95th% = 2.169) to 1.468 at the 24th week's
      gestation (5th% = 1.057, 95th% = 1.878). The predicted RI value of the
      subplacental spiral artery also decreased from 0.408 at the 13th week's gestation
      (5th% = 0.193, 95th% = 0.623) to 0.312 at the 24th week's gestation (5th% =
      0.148, 95th% = 0.477). CONCLUSIONS: Normal blood flow resistance of the
      subplacental spiral arteries at 13-25 gestational weeks decreases progressively
      with advancing gestational age. The fact suggests that trophoblastic invasion of
      the spiral arteries occurred continuously throughout normal second-trimester
      pregnancies.

PMID- 9248123
TI  - Lamotrigine as add-on therapy in adult patients with refractory epilepsy.
AB  - BACKGROUND: Lamotrigine (LTG), one of the newly developed antiepileptic drugs, is
      efficacious in treating both partial and generalized seizure disorders including
      Lennox-Gastaut syndrome. Its effect as an add-on therapy was evaluated in 41
      adult Chinese patients with refractory epilepsy. Five of the patients were Lennox
      Gastaut syndrome and 36 patients had partial epilepsy. METHODS: We started LTG at
      25 mg or 50 mg per day, respectively, depending on whether the patients were
      simultaneously taking valproate (VPA) or not. Then, LTG was increased in steps to
      maximal dosage (200 mg or 400 mg per day) within seven weeks and maintained for
      three months while pre-existing antiepileptic drugs remained unchanged. The
      efficacy of LTG therapy was assessed by the reduction in the overall seizure
      frequency. Hematological and biochemical parameters were checked before and after
      the trial in all patients. RESULTS: In all, 38 patients completed the trial.
      Twenty-two patients (57.9%) had > or = 50% reduction in seizure frequency,
      including four patients with Lennox-Gastaut syndrome and 18 patients with partial
      seizures. Among the patients with partial epilepsy, there was no significant
      difference in the efficacy of LTG whether the seizures were of temporal or extra
      temporal origin (p = 0.577). In addition, the efficacy was not determined by the
      concomitant use of VPA (p = 0.189). Thirteen patients (31.7%) complained of
      adverse experiences, usually mild and dose-dependent. LTG had to be discontinued
      in only two patients (4.9%) due to severe side effects. The change in blood cell
      counts and biochemistry profiles was not significant in any of the patients.
      CONCLUSIONS: We conclude that LTG is an efficacious and safe antiepileptic drug
      for add-on therapy in adult patients with refractory epilepsy.

PMID- 9248122
TI  - Measurement of the radiation doses absorbed by jaw bones during irradiation of
      nasopharyngeal cancers.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) occurs more frequently for Chinese
      than for other ethnic groups. The most common treatment for NPC is radiotherapy,
      but there is no report of the doses of radiation absorbed by the mandibular and
      maxillary bones, although exposure to radiation is one of the most important
      references for those patients who need to have oral surgical treatments. METHODS:
      Thermoluminescent dosimeter (TLD) was used to measure radiation absorbed by a
      rando phantom and cancer patients. RESULTS: The results showed that the doses
      absorbed by the mandible and maxilla depend on the dose applied, field size, and
      field shape. In the rando phantom, the range of absorption in the mandible was,
      for the central incisor 1.89-3.36 Gy, canine 1.96-3.78 Gy, bicuspid 2.24-14.14
      Gy, second molar 4.34-31.92 Gy, internal pterygoid muscle region 70 Gy. In the
      maxilla the range was, for the central incisor 2.17-2.94 Gy, canine 2.24-3.36 Gy,
      bicuspid 3.15-4.41 Gy, second molar 7.00-7.42 Gy. In nasopharyngeal carcinoma
      patients, the mean radiation absorbed by the bicuspid vestibular region of the
      mandible was 3.09 Gy, by the bicuspid vestibule of the maxilla 3.35 Gy and by the
      midline vestibule 2.31 Gy. The radiation doses absorbed by maxilla and mandible
      from the incisor to the second premolars were less than 20% of the dose to the
      primary tumor. CONCLUSIONS: The doses absorbed by the mandible and maxilla are
      relatively low in NPC patients receiving radiation therapy.

PMID- 9248124
TI  - Association of secundum atrial septal defect and mitral lesion in childhood: a
      case report.
AB  - The association of secundum atrial septal defect (ASD) and congenital or acquired
      mitral lesions is rare. Only one case of secundum ASD and mitral lesion, in a
      three-year-old girl, has been encountered over a three-year period in this
      hospital. Diagnosis was not difficult with echocardiography, and was confirmed by
      operation. Surgical procedures including repair of ASD and annuloplasty of the
      mitral valve were performed under cardiopulmonary bypass. The mitral valve lesion
      was found during the operation to be of a congenital origin. Mitral lesions
      should not be neglected, and repair should be attempted even in a pediatric
      patient. Otherwise, anatomical and functional disorders of the mitral valve may
      develop at the early postoperative stage.

PMID- 9248125
TI  - Retroperitoneal bronchogenic cyst: a case report.
AB  - Only a few subdiaphragmatic bronchogenic cysts are described, and their
      occurrence in the retroperitoneum is extremely rare. So far, only a few cases
      have been reported in the English-language literature. The pathogenesis is caused
      by the pinching off of irregular lung budding of the primitive ventral foregut,
      with aberrant migration into the abdomen before fusion of the diaphragm during
      embryonal development. A unique case with clinical, radiographic, surgical
      finding is presented. Final pathological findings confirmed the diagnosis of
      retroperitoneal bronchogenic cyst without other associated congenital anomalies.
      Retroperitoneal bronchogenic cyst, although rare, should be considered in the
      differential diagnosis in the retroperitoneal mass. This rare case is described
      and the relevant literature, reviewed.

PMID- 9248126
TI  - Fulminant hepatic failure as the first manifestation of Wilson disease: a report
      of two cases.
AB  - Two cases of fulminant hepatic failure as a first manifestation of Wilson disease
      are reported. They were diagnosed as acute hemolytic anemia initially, and took a
      fatal course despite intensive medical therapy. The main object of this report is
      to emphasize that Wilson disease must be included in the differential diagnosis
      of fulminant hepatic failure in children. Liver transplantation is the only
      effective means of treatment in patients presenting with fulminant hepatic
      failure, but this procedure is difficult to perform because of insufficient organ
      donation in Taiwan. The best treatment for Wilson disease is prevention through
      diagnosis at a presymptomatic stage, and institution of life-long therapy with D.
      penicillamine.

PMID- 9248127
TI  - The VIP regimen effective treatment to refractory choriocarcinoma: a case report.
AB  - This is a case report of a female patient who tried another regimen after EMA-CO
      regimen failed. A 30-year-old female, gravida 4, para 2, abortus 2, blood
      grouping O (grouping B of her husband), was a victim of choriocarcinoma of the
      uterus and was resistant to multiple combination regimens of chemotherapy (EMA
      CO, EMA-PE, BEP). She was finally cured by the VIP regimen of chemotherapy. The
      VIP regimen may be considered as an effective protocol to cure refractory
      choriocarcinoma.

PMID- 9248128
TI  - Annual report of the Australian Gonococcal Surveillance Programme 1996.
AB  - In 1996 the Australian Gonococcal Surveillance Programme (AGSP) examined 2,753
      isolates of Neisseria gonorrhoeae. The source of isolates, site of infection and
      antibiotic susceptibility patterns showed considerable regional variation.
      Strains examined in Adelaide, Sydney and Melbourne were predominantly from male
      patients where rectal and pharyngeal isolates were common. Cases in other centres
      had a much lower male:female ratio and most were genital tract isolates.
      Resistance to the penicillin and quinolone groups of antibiotics was highest in
      Sydney and Melbourne. Gonococcal resistance to the penicillins was similar to
      previous years. Quinolone-resistant Neisseria gonorrhoeae (QRNG) were isolated
      mostly from overseas travellers. However, some local transmission of QRNG was
      documented in Sydney. All isolates were sensitive to spectinomycin and
      ceftriaxone.

PMID- 9248129
TI  - Ross River virus in a joint military exercise.

PMID- 9248130
TI  - Communicable diseases surveillance.

PMID- 9248132
TI  - Pars tensa perforation with cholesteatoma.

PMID- 9248131
TI  - Medical Injury Compensation Reform Act: good or bad?

PMID- 9248133
TI  - Vocal fold cysts and reactive nodules: differentiation from bilateral nodules.

PMID- 9248134
TI  - Endoscopic view of mucociliary transport following middle meatal antrostomy.

PMID- 9248135
TI  - Use of magnetic resonance imaging and magnetic resonance angiography in diagnosis
      of sigmoid sinus thrombosis.
AB  - Magnetic resonance angiography is an established radiologic technique which is
      rapidly becoming useful in imaging the head and neck. Currently, this imaging
      modality is important in the diagnosis of sigmoid sinus thrombosis caused by
      otologic disease. Since the introduction of antibiotic therapy, the percentage of
      deaths attributed to intracranial complications from otitic disease has decreased
      from 2.5 to approximately 0.25% of documented deaths. Also, the incidence of
      sinus thrombosis within this group has decreased, but it is still a serious and
      potentially lethal condition. Sinus thrombosis is suspected clinically when
      mastoid disease progresses, with picket fence fever pattern, chills, headaches
      and signs of papilledema. Definitive diagnosis is necessary before surgical
      treatment. The Queckenstedt test is unreliable, computed tomography is better
      suited for demonstrating thrombosis of the sagittal sinus rather than the sigmoid
      sinus, and conventional angiography (although it provides excellent
      visualization) has the hazard of ionizing radiation and requires vessel puncture
      and the use of intraarterial contrast agents. We present two cases of thrombosis
      of the sigmoid sinus as an intracranial otologic complication which were
      diagnosed definitively with magnetic resonance imaging and magnetic resonance
      angiography. The combination of magnetic resonance imaging, which showed the
      thrombosis displaying abnormal signal intensity, and magnetic resonance
      angiography, which demonstrated the absence of flow in the sinus, was an ideal
      diagnostic tool. For both patients, treatment consisted of mastoidectomy, sigmoid
      sinus decompression and antibiotics.

PMID- 9248136
TI  - Delayed pharyngoesophageal perforation following anterior spine surgery.

PMID- 9248137
TI  - Giant cell reparative granuloma of the maxilla.
AB  - Giant cell reparative granuloma (GCRG) is a rare nonneoplastic proliferative
      lesion of unknown etiology. It most commonly occurs in the mandible, but also
      occurs in other bones of the facial skeleton and cranial vault. Two cases of GCRG
      arising from the maxilla are presented. Histological and radiological features,
      and the pertinent literature on the subject are reviewed.

PMID- 9248139
TI  - Preoperative assessment of the implantable middle ear pump system using CT scans
      and conventional X-rays of the temporal bone.
AB  - A completely implantable micropump system for drug delivery has recently been
      developed. After implantation in the temporal bone, this microdosage system
      enables application of drugs into the middle ear and round window area.
      Successful application of this new technology depends upon a suitable fit of the
      micropump within the patient's temporal bone. To obtain information about the fit
      before surgery, we analyzed 50 cadaver temporal bone specimens before total
      mastoidectomy, using conventional X-ray and spiral CT scans for water volume
      determination. Spiral CT is a feasible method for preoperative planning of the
      surgical implantation of the implantable middle ear micropump system (TI-DDS).
      The best parameter for a preoperative judgment is the volume of the mastoid
      cavity, as determined by CT. Implantation may be recommended when the mastoid
      volume, as measured by CT, is greater than 6.6 ml. To be certain that the
      implantable drug delivery system will be implantable, a cut-off value of 9.3 ml
      seems to be advisable. Spiral CT imaging is of great value as a tool for testing
      implantation preoperatively. The imaging is accomplished in approximately 30
      seconds. Our preliminary results with cadaveric temporal bones are encouraging.
      Further studies are needed in order to transfer the results to a clinical
      implantation situation.

PMID- 9248138
TI  - Swallowing and pharyngeal function in postoperative pharyngeal cancer patients.
AB  - This study examines the pharyngeal phase of swallowing after the resection of
      pharyngeal cancer, and focuses on the pharynx as a functional organ. The purpose
      of the study was to obtain information on both reconstruction and rehabilitation
      in cases of surgically treated pharyngeal cancer. The records of 21 consecutive
      patients who underwent surgical treatment of oropharyngeal and hypopharyngeal
      squamous cell carcinoma between 1990 and 1993 were reviewed. Functional results
      following surgery were graded on a numerical scale in three categories:
      pharyngeal swallow, laryngeal and lower airway protection, and oral alimentation.
      Three treatment groups were observed: group 1 = transoral excision with primary
      closure (six patients); group 2 = composite resection with primary closure (nine
      patients); and group 3 = composite resection with deltopectoral or pectoralis
      major flap closure (six patients). Comparison of pharyngeal swallow and laryngeal
      protection functions showed no significant difference between the three groups.
      However, oral alimentation performance in group 1 was significantly better than
      in group 3, and groups 1 and 2 achieved a similar level. In patients with T3 and
      T4 tumors postoperative function was poor and no difference in postoperative
      function was demonstrated between patients undergoing reconstruction with primary
      closure and patients undergoing reconstruction with deltopectoral or pectoralis
      major flaps. Patients with T3 and T4 tumors experienced impaired postoperative
      function regardless of the method of reconstruction used. This is not a
      condemnation of the surgical treatment of advanced pharyngeal tumors, but rather
      a suggestion that other reconstruction techniques be considered.

PMID- 9248140
TI  - Intranasal meningoencephalocele and the use of fibrin glue.
AB  - Meningoencephaloceles are rarely seen in adults. This case report illustrates the
      management of a large intranasal meningoencephalocele in an adult man. Excision
      of this lesion resulted in a defect in the cribriform plate which was closed
      using tissue and fibrin glue.

PMID- 9248141
TI  - Unilateral conductive hearing loss secondary to a high jugular bulb in a
      pediatric patient.
AB  - A high jugular bulb is not an uncommon otologic anomaly. It may be noted as an
      incidental finding on physical exam, middle ear surgery, or computed tomography
      of the temporal bones. Frequently the patient is asymptomatic, but a high jugular
      bulb can occasionally cause tinnitus or conductive hearing loss. The case of a
      seven-year-old black male with unilateral conductive hearing loss secondary to a
      high jugular bulb is presented. The diagnosis, differential diagnosis, and
      management of a conductive hearing loss associated with a high jugular bulb are
      discussed.

PMID- 9248142
TI  - [Protection of cultured mammalian cells by rebamipide].
AB  - Rebamipide which is used as a drug for gastritis and stomach ulcer has large
      capability for OH radical scavenging. It is expected that rebamipide has
      protective effect against ionizing radiations. The present paper deals with
      protective effect of rebamipide for cultured mammalian cells exposed to ionizing
      radiations. As rebamipide is insoluble in water, three solvents were used to
      dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide
      (DMFA) and 0.02 N NaOH was added to the cells in Eagle's minimum essential medium
      (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X
      rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal
      calf serum and incubated for 7 days in a CO2 incubator to form colonies.
      Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its
      OH radical scavenging capability. However, the protective effect of rebamipide
      dissolved in DMSO was about half of that expected by its radical scavenging
      capability and that of rebamipide dissolved in DMFA was not observed. Uptake of
      rebamipide labeled with 14C increased with increasing contact time with
      rebamipide. These rebamipide mainly distributed in nucleous rather than
      cytoplasm.

PMID- 9248143
TI  - Clinical efficacy of interferon therapy for chronic hepatitis C in the Kita
      Kyushu District of Japan.
AB  - The Kita-Kyushu district in Japan is one of the areas known to have a quite high
      prevalence of HCV infection. We analyzed the results of interferon therapy
      administered to 50 chronic hepatitis C patients living in this area (33 males and
      17 females; ages between 28 and 65 years old). Interferon-alpha (human
      lymphoblast interferon, HLBI), 6 million units/day, was administered for 24
      consecutive weeks. Before the therapy, the HCV levels, HCV-RNA genotype, and
      sequence of hypervariable region (HVR) of HCV were examined. Patients who were
      HCV-RNA negative and ALT < or = 30 IU/L at the completion of therapy and in the
      6th month after the completion of therapy, were determined as complete responders
      (CR). In this study, 10 of 50 patients (20%) were CR. Among male patients, there
      were no CR in each age group, whereas among female patients aged over 40 years
      old, there were no CR. The number of patients with low virus levels was larger in
      the genotype 2a/2b cases than in the genotype 1b cases. HVR sequences varied
      extensively, and had no correlation to interferon efficacy. Multivariate analysis
      showed that the pre-treatment HCV level is the most important predictor.

PMID- 9248144
TI  - Is patellar height really lower after high tibial osteotomy?
AB  - It has been reported that patellar position becomes lower after the high tibial
      osteotomy. However, the most commonly used methods for determining patellar
      height, namely, the Insall-Salvati and Blackburne-Peel methods, use a reference
      point on the tibia. Therefore, when a surgery is performed on the proximal tibia,
      the point of reference itself shifts, which may generate spurious values
      indicating a change when nothing has occurred. We developed a new method for
      measuring the change in patellar height in relation to the femur under the
      condition that the patella articulates with the femur, and not with the tibia.
      Contrary to published reports, we found that the patella height is unchanged or
      moves slightly proximal in relation to the femur following high tibial osteotomy.

PMID- 9248145
TI  - The status of local health care safety nets.
AB  - This paper examines variations in the composition, concentration, financing, and
      community context of local health care "safety nets" and the market pressures
      that they face. It also reviews financing mechanisms that support these systems
      and strategies being undertaken to retain publicly insured patients. As safety
      net providers compete more aggressively, the availability of the public health,
      behavioral health, and social services they provide may be affected. Communities
      may have to consider more explicit investments in these "public goods" if
      competitive markets remove existing cross-subsidies.

PMID- 9248146
TI  - Denver Health: initiatives for survival.

PMID- 9248147
TI  - Beyond the safety net in Dallas.

PMID- 9248148
TI  - The evolution of support for safety-net hospitals.
AB  - The federal government, mostly through the Medicare and Medicaid programs, has
      created and maintained a set of structural mechanisms to support uncompensated
      care and clinical education: disproportionate-share hospital payments and direct
      and indirect graduate medical education payments. This paper provides a history
      of how these traditional supports have evolved. We note that the need to reduce
      federal and state spending threatens the level of these payments, while changes
      in the health care delivery system highlight a range of design and technical
      inadequacies in the current support mechanisms.

PMID- 9248149
TI  - Financing graduate medical education: the search for new sources of support.
AB  - Rapid and profound changes in the public and private markets for health care
      services are posing multiple challenges to the complex and inter-dependent system
      for financing medical education. In this paper, we examine a wide range of
      potential sources of financial support for medical education, provide data on the
      revenue yield under different assumptions, and assess each option against the
      criteria of equity, adequacy, collectibility, and effects/ consequences. We also
      describe and analyze recent legislative proposals designed to reform the
      financing system for medical education and provide an overall assessment of the
      policy environment confronting such proposals.

PMID- 9248151
TI  - Insuring children: the next steps.

PMID- 9248150
TI  - Incremental approaches to covering uninsured children: design and policy issues.
AB  - More than 10.5 million children were uninsured throughout 1995. The number of
      uninsured children remains high, even in the face of continued expansions of
      Medicaid designed to cover low-income children. As a result, interest persists in
      developing additional approaches for covering uninsured children. Efforts to
      attract more uninsured children will entail important trade-offs between the
      federal costs of the program (and its political viability) and the number of
      uninsured children who enroll.

PMID- 9248152
TI  - Politics and compromise: Senator Jim Jeffords. Interview by John K. Iglehart.

PMID- 9248153
TI  - Medicaid managed care and community providers: new partnerships.
AB  - Growing enrollment in managed care plans among Medicaid recipients represents a
      new market for these plans but presents challenges to those providers that
      traditionally have served this population. To continue serving Medicaid patients,
      community-based providers must develop contracts or other types of partnerships
      with Medicaid-contracting health plans. This paper reviews the challenges to such
      collaboration and discusses the practical issues that plans and community-based
      providers must resolve to develop productive working relationships. Keys to
      successful collaboration are identified. Ways in which federal and state
      governments can help the collaborative process are suggested.

PMID- 9248154
TI  - The politics and economics of mental health 'parity' laws.
AB  - The enactment of the Domenici-Wellstone amendment in September 1996, which calls
      for the elimination of certain limits on coverage for mental health care under
      private insurance, is being hailed as a major step forward in the quest for
      "parity" in mental health coverage. Parity legislation is being introduced in a
      number of state legislatures and is finding new enthusiasm in Congress. In this
      paper we consider the efficiency rationale for these laws and examine their
      likely impact in the era of managed care. We conclude that although such
      successes represent important political events, they may offer only small gains
      in the efficiency and fairness of insurance markets.

PMID- 9248155
TI  - Covering mental health and substance abuse services.

PMID- 9248156
TI  - Characteristics and growth of managed behavioral health care firms.

PMID- 9248157
TI  - The public sector in health care: evolution or dissolution?

PMID- 9248158
TI  - The safety-net role of international medical graduates.

PMID- 9248159
TI  - Tracking health care costs: an update.

PMID- 9248160
TI  - The consumer health plan value survey: round two.

PMID- 9248161
TI  - A changing picture of uncompensated care.

PMID- 9248162
TI  - Use and abuse of the medical loss ratio to measure health plan performance.
AB  - This paper examines the use and abuse of the medical loss ratio in the
      contemporary health care system and health policy debate. It begins with a survey
      of the ways in which the medical loss ratio has been interpreted to be something
      it is not, such as a measure of quality or efficiency. It then analyzes key
      organizational features of the emerging health care system that complicate
      measures of financial performance, including integration between payers and
      providers, diversification of payers across multiple products and distribution
      channels, and geographic expansion across metropolitan and state lines. These
      issues are illustrated using medical loss ratios from a range of nonprofit and
      for-profit health plans. The paper then sketches a strategy for improving the
      public's understanding of health plan performance as an alternative to continued
      reliance on the flawed medical loss ratio. This strategy incorporates data on
      structure and process, service quality, and financial performance.

PMID- 9248163
TI  - State health care reform in Massachusetts.

PMID- 9248164
TI  - Lessons from Arizona's Medicaid managed care program.

PMID- 9248166
TI  - Will minority physician supply meet U.S. needs?
AB  - We project the future racial and ethnic composition of the U.S. physician
      workforce under different assumptions. Our projections show that reaching racial
      and ethnic population parity with a managed care-based requirement of 218
      physicians per 100,000 population would require the number of first-year
      residents to roughly double for Hispanic and black physicians, triple for Native
      American physicians, and be reduced by about two-fifths for white physicians and
      two-thirds for physicians of Asian or Pacific Island origin.

PMID- 9248165
TI  - The VA health care system: an unrecognized national safety net.
AB  - The dominance of local health care markets in conjunction with variable public
      funding results in a national patchwork of "safety nets" and beneficiaries in the
      United States rather than a uniform system. This DataWatch describes how the
      recently reorganized Department of Veterans Affairs serves as a coordinated,
      national safety-net provider and characterizes the veterans who are not supported
      by the market-based system.

PMID- 9248167
TI  - What types of hospitals form the safety net?
AB  - This analysis describes hospitals that provide large amounts of uncompensated
      care and hospitals with sizable teaching programs, using data from the American
      Hospital Association. Despite current public financial support mechanisms, safety
      net hospitals have a lower average total margin and a greater percentage with
      negative total margins than other groups of hospitals. For graduate medical
      education, however, the current public financial supports have assisted teaching
      hospitals with the largest training programs in maintaining their financial
      viability, although teaching hospitals' average total margins remain below those
      of nonteaching hospitals.

PMID- 9248168
TI  - A profile of uncompensated hospital care, 1983-1995.
AB  - This DataWatch examines national trends in the provision of uncompensated
      hospital care. It shows that rapid growth from 1983-1986 was followed by modest
      growth through 1990, a time during which managed care was becoming established in
      some regions. There was then another spurt in uncompensated care from 1991-1993,
      a period that corresponds to sizable increases in disproportionate-share
      payments. Uncompensated care growth again slowed through 1995. The increase in
      uncompensated care levels after 1988 appears not to have kept pace with growth in
      hospital expenses or the number of uninsured. However, the trend data do not
      suggest a large-scale reduction of effort.

PMID- 9248169
TI  - State trends in hospital uncompensated care.
AB  - In recent years hospital uncompensated care has been declining in the seven
      states studied here: California, Florida, Washington, Connecticut, Maryland, New
      Jersey, and New York. We document these declines and compare trends in
      uncompensated care in safety-net and other hospitals between the early 1980s and
      the early to mid-1990s. We discuss state responses to deal with the declines in
      hospital uncompensated care and their likely impact on the observed trends.

PMID- 9248170
TI  - Academic health centers in competitive markets.
AB  - Academic health center (AHC) hospitals and other major teaching hospitals have
      funded a portion of their academic missions through patient care revenues. Using
      all-payer state discharge data, this DataWatch presents information on how these
      institutions are being affected by market changes. Although AHCs are not as
      successful as other hospitals are in attracting managed care patients,
      competitive pressures had not eroded AHCs' financial status as of 1994. However,
      increasing enrollment in managed care and potential changes in both Medicare and
      Medicaid suggest that pressure on the financing of these institutions' social
      missions will continue to grow over time.

PMID- 9248171
TI  - Improving workers' compensation health care.

PMID- 9248172
TI  - A look inside Medicaid managed care.

PMID- 9248173
TI  - An open letter to Alain Enthoven.

PMID- 9248174
TI  - Nonprofit hospitals: bargain prices?

PMID- 9248175
TI  - Medical economics in therapeutic endoscopy: a critical appraisal.

PMID- 9248176
TI  - Primary pulmonary hypertension in non-cirrhotic portal fibrosis.
AB  - BACKGROUND: Primary pulmonary hypertension (PPH) has been reported in association
      with cirrhosis and extrahepatic portal venous obstruction; reports of PPH in
      noncirrhotic portal fibrosis (NCPF) are few. AIM: To evaluate pulmonary arterial
      pressure in patients with NCPF. METHODS: Twenty two patients with NCPF underwent
      hemodynamic studies for pulmonary arterial pressure after excluding secondary
      causes of pulmonary hypertension. Hemodynamic studies were carried out through
      the femoral route using 7F Swan-Ganz catheter. Splenoportal venography was done
      by percutaneous splenic puncture. RESULTS: The mean pulmonary arterial pressure
      was 12.9 +/- 3.1 mmHg with pulmonary capillary wedge pressure of 8.3 +/- 2.1 mmHg
      in 20 of 22 cases; in the remaining two cases, the corresponding pressures were
      30 mmHg and 28 mmHg and 13 mmHg and 12 mmHg, respectively. CONCLUSION: Two of 22
      patients with NCPF had PPH. PPH can thus develop without hepatocellular failure
      or recurrent embolization from portal axis thrombosis as has been described in
      cirrhosis.

PMID- 9248177
TI  - Primary gastrointestinal lymphoma--disease spectrum and management: a 15-year
      review from north India.
AB  - OBJECTIVE: To analyze retrospectively the disease spectrum and outcome of primary
      gastrointestinal lymphoma (PGIL) in a tertiary referral center in north India.
      MATERIAL: Seventy five patients presenting with PGIL between January 1971 and
      December 1985 were evaluated. RESULTS: The 49 males and 26 females were aged 3.5
      69 years (mean 34) at presentation. Abdominal pain, weight loss and vomiting were
      cardinal symptoms at presentation; the stomach was the most common site of
      involvement. Histologically, a majority of patients were classified as having
      diffuse poorly-differentiated lymphocytic lymphoma (46.7%) and diffuse
      histiocytic type (30.7%). Twenty seven (36%) patients had stage I disease, 31
      (40%) stage II, 11 (14.7%) stage III, and 6 (8%) stage IV. At laparotomy, primary
      resection and anastomosis was carried out in 66 patients, while only biopsies
      were taken in nine. Forty eight patients received adjuvant radiation with or
      without chemotherapy. The mean follow-up was 3.9 years (range 1-14). The 5-year
      actuarial survival was 34%, 25% and 16% for stages I, II, and higher-stage
      disease, respectively. The survival was significantly better (p < 0.01) for
      gastric location (44%) compared to other sites (24%). CONCLUSION: PGIL was more
      common in the 3rd and 4th decades of life, with the stomach being the predominant
      site of involvement. Survival was better among patients with stages I and II
      disease, and gastric location of lesion.

PMID- 9248178
TI  - Endoscopic palliation of malignant obstructive jaundice using resterilized
      accessories: an audit of success, complications, mortality and cost.
AB  - OBJECTIVE: To assess the success, complications and cost of endoscopic
      endoprosthesis placement for palliation of obstructive jaundice caused by
      malignancy. METHODS: Four hundred and two consecutive patients with obstructive
      jaundice due to nonresectable malignancy undergoing endoscopic stenting were
      studied. Commercial or home-made 7F or 10F endoprostheses were placed using minor
      modifications of the standard technique. The accessories were sterilized and
      reused. RESULTS: Endoprosthesis placement was successful in 291 patients (72.4%,
      95% CI 67.7-76.7)-241 in one attempt, 49 in two attempts, and one in three
      attempts. Fifty nine patients (14.6%, 95% CI 11.4-18.6) had procedure-related
      complications, including cholangitis (30), pancreatitis (15), perforation (3) and
      bleeding (11). The incidence of cholangitis was significantly higher in
      bifurcation blocks than in other lesions (17.6% vs 4.7%, p = 0.0005). The success
      rate did not differ between distal and proximal lesions (68.1% vs 72.9%). The
      procedural cost per patient could be reduced from Rs 14,850 to Rs 6565 by reusing
      accessories after sterilization, and using home-made stents. CONCLUSIONS:
      Endoscopic endoprosthesis placement is a safe and effective method for palliation
      of malignant obstructive jaundice. Preparation of indigenous stents and reuse of
      accessories can reduce the cost of the procedure by over 50%.

PMID- 9248179
TI  - Spectrum of liver diseases in HIV infection.
AB  - BACKGROUND: Most earlier reports on the spectrum of liver diseases in HIV
      infected individuals originated from the West. OBJECTIVE: To study the spectrum
      of liver diseases in HIV-infected individuals. METHODS: Seventy four consecutive
      HIV-positive patients (57 men; age range 23-75 years, mean 34) were studied
      prospectively with clinical evaluation, liver function tests, ultrasonography,
      radioisotope liver scan, markers of hepatitis B (HBV) and C (HCV) viruses, and
      liver histology whenever necessary. RESULTS: Thirty four patients (45%) were
      chronic alcoholics. Mean (SD) absolute lymphocyte count was 2521 (1271)/mm3;
      count < 2000/ mm3 was present in 20 patients. Serum bilirubin, transaminases and
      alkaline phosphatase levels were elevated in 13%, 13% and 24% of patients,
      respectively. Ultrasonography detected an abscess in two patients (tuberculous-1,
      amebic-1). Evidence of exposure to HBV was present in 81% (HBsAg-12, hepatitis B
      core and/or surface antibody-48); anti-HCV antibody was positive in 29.7%. Five
      patients with liver tuberculosis (granuloma-4, abscess-1) had AFB either in liver
      tissue or lymph nodes. CONCLUSION: Chronic alcoholism, HBV and HCV infection,
      hepatic tuberculosis, and evidence of other liver disease were common in patients
      with HIV infection.

PMID- 9248180
TI  - Ksharsootra (medicated seton) treatment for fistula-in-ano.
AB  - BACKGROUND: Recurrence and incontinence are common after conventional surgery for
      fistula-in-ano. Medicated seton (ksharsootra) is a time-tested therapy. METHODS:
      Seton treatment was given to 114 patients with anal fistulae. The initial loose
      seton was changed weekly to achieve fistulotomy. RESULTS: Application of non
      medicated seton did not show any cutting action; hence all patients were treated
      with ksharsootra after 3 weeks. Anal discharge (n = 114) and burning pain (35)
      were noted in the first 48-72 hours. The cut-out rate was around 1 cm/week, with
      mean cut-out time 8.3 weeks (range 3-18). All wounds healed well and patients
      remained ambulatory. Local induration developed in 18 patients; four had an
      abscess. There was no incontinence or recurrence over a follow-up of 6 months to
      2 1/2 years. CONCLUSIONS: Ksharsootra treatment for anal fistulae is safe and
      effective, with low complication rates.

PMID- 9248181
TI  - Epidemiology of digestive cancers in India. I. General principles and esophageal
      cancer.

PMID- 9248182
TI  - Magnetic resonance cholangiography as sole pre-operative determinant of
      resectability in hilar cholangiocarcinoma.

PMID- 9248183
TI  - Intestinal strongyloidiasis--a rare opportunistic infection.
AB  - We describe the features of intestinal strongyloidiasis in six patients; five of
      them were immunosuppressed (four on corticosteroids, one with chronic renal
      failure). Vomiting and diarrhea were the predominant symptoms. Duodenal mucosa on
      endoscopy varied from normal to severe ulceration. Albendazole 400 mg/day for two
      weeks was effective. This condition should be considered in immunosuppressed
      individuals with gastrointestinal symptoms, especially since these symptoms may
      be mistakenly attributed to the underlying disease.

PMID- 9248185
TI  - Subacute hepatic failure in hepatitis A.
AB  - Hepatitis A is usually thought to be innocuous. We report a woman who developed
      subacute hepatic failure due to hepatitis A and died of the disease.

PMID- 9248184
TI  - Stricturoplasty for benign biliary stricture.

PMID- 9248186
TI  - Transection of common bile duct following blunt injury to abdomen.
AB  - Isolated complete transection of the common bile duct due to blunt abdominal
      trauma is rare. We report such a case following an assault.

PMID- 9248187
TI  - Gastric tuberculosis presenting with hematemesis.
AB  - The stomach is rarely involved by tuberculosis. We report a patient with gastric
      tuberculosis who presented with exsanguinating hematemesis.

PMID- 9248188
TI  - Morgagni hernia in a neonate with ventricular septal defect.
AB  - A neonate with Morgagni hernia and ventricular septal defect is reported.
      Presentation of Morgagni hernia in neonates is rare, but when it does, it is
      associated with other congenital anomalies.

PMID- 9248189
TI  - Primary gastric lymphoma in a boy.
AB  - Primary gastric lymphoma is an extremely uncommon entity in children, and diffuse
      large-cell-type lymphoma in this age group is still rarer. An 11-year-old boy
      with primary gastric lymphoma who responded to CHOP regime is reported.

PMID- 9248190
TI  - Infectious mononucleosis hepatitis: report of two patients.
AB  - Icteric hepatitis and fulminant hepatic failure (FHF) are rare in infectious
      mononucleosis (IM). We report two patients with icteric IM hepatitis; one died
      after developing FHF, the other recovered uneventfully. Epstein-Barr virus
      infection causing hepatitis and FHF should be suspected when tests for other
      hepatotrophic viral infections are negative.

PMID- 9248191
TI  - Colonic chemobezoar--intestinal obstruction due to barium inspissation.
AB  - A 72-year-old man presented with constipation of 45 days' duration, with history
      suggestive of recurrent episodes of subacute intestinal obstruction relieved by
      passage of fluid and flatus; he had noticed an abdominal lump 30 days prior.
      Examination revealed a lump corresponding to the contours of the entire large
      intestine. X-ray showed barium outlining the colon. Enquiry revealed that he had
      undergone a barium enema study 10 days prior to appearance of the lump. The
      diagnosis of barium inspissation was confirmed at laparotomy; total colectomy
      with ileo-rectal anastomosis was done.

PMID- 9248192
TI  - Hepatitis E virus and Salmonella paratyphi A coinfection.
AB  - We report a patient with simultaneous Salmonella paratyphi A and hepatitis E
      virus infection. The possibility of coinfection with water borne diseases in
      India is emphasized.

PMID- 9248193
TI  - Collision tumor with three components at esophagogastric junction.
AB  - We report a 70-year-old man with a collision tumor consisting of three neoplasms
      at the gastroesophageal junction. The component tumors were squamous carcinoma at
      the esophageal and, adenocarcinoma at the gastric end, and leiomyoma within.

PMID- 9248194
TI  - Ceruloplasmin as an antioxidant in duodenal ulcers.

PMID- 9248195
TI  - Dermatoglyphic patterns in gallstone disease.

PMID- 9248196
TI  - Number of breath samples required for detection of lactose intolerance by lactose
      hydrogen breath test.

PMID- 9248197
TI  - Comparative evaluation of serology and polymerase chain reaction for hepatitis C
      viral infection in liver diseases.

PMID- 9248198
TI  - Improvisation of indigenous pneumatic dilator.

PMID- 9248199
TI  - Partington's pancreaticojejunostomy does not need modification.

PMID- 9248200
TI  - Screwing a carrot out of the rectum.

PMID- 9248201
TI  - Endoscopic retrieval of impacted spigot from gastrostomy tube.

PMID- 9248202
TI  - Hepatoma cast obstructing common bile duct: not always a terminal event.

PMID- 9248203
TI  - Inadvertent banding of laryngeal mucosa during endoscopic variceal band ligation.

PMID- 9248204
TI  - Primary biliary cirrhosis with pruritus in India.

PMID- 9248205
TI  - Ethical problems in gastroenterology.

PMID- 9248206
TI  - Dengue haemorrhagic fever outbreak in October-November 1996 in Ludhiana, Punjab,
      India.
AB  - An epidemic of haemorrhagic fever broke out in Ludhiana in October and November
      1996. Persons of all age groups were affected with preponderance of young adults.
      Haemorrhagic manifestations like rashes, epistaxis, bleeding from the gums and
      haematemesis were observed. The cause of fever was investigated. Serum samples
      collected at random from 71 patients were tested by ELISA for dengue types 1-4
      IgM antibodies. These were positive in 96.7 per cent of cases. Immunoblot testing
      for IgM and IgG for all serotypes of dengue virus were positive in 90.2 and 73.2
      per cent of the serum samples respectively. The haemorrhagic fever was
      serologically proven to be due to dengue virus.

PMID- 9248207
TI  - Virus isolation from wild-caught mosquitoes during a Japanese encephalitis
      outbreak in Kerala in 1996.
AB  - Out of 5357 wild-caught mosquitoes in 163 pools tested for virus using antigen
      capture ELISA and an insect-bioassay (inoculation into Toxorhynchites splendens
      larvae and identification by IFA using JE virus-specific monoclonal antibody), 16
      flavivirus isolations were made of which 12 (75%) were identified as JE virus. Of
      the 12 JE virus isolations, 7 were from Culex tritaeniorhynchus, 3 from Mansonia
      uniformis and 1 each from Ma. indiana and Anopheles subpictus. Four isolations
      from Mansonia species for the first time reported here are noteworthy.

PMID- 9248208
TI  - An epidemic of diarrhoea in south India caused by enteroaggregative Escherichia
      coli.
AB  - A diarrhoeal epidemic in a village close to Vellore was investigated in January
      1996. Faecal samples were obtained from 20 subjects with diarrhoea and from 11
      individuals without diarrhoea (controls) and were examined for bacterial, viral
      and parasitic enteropathogens. Water samples from all sources in the village were
      analysed. The epidemic affected all age groups (overall attack rate 15%). The
      mean duration of diarrhoea was 11 days. Individuals who consumed water
      exclusively from a borewell had a lower relative risk (RR) of disease (0.14, 95%
      Cl 0.02-1.01) compared to users of two open wells (RR 6.93, Cl 0.99-48.66 and RR
      7.81, Cl 1.02-59.79, respectively). No conventional bacterial enteropathogens
      were isolated from the stool samples. Enteroaggregative Escherichia coli (EAggEC)
      were identified in the stool of 11 of 20 subjects with diarrhoea, and in 1 of 11
      control samples (P = 0.02). All the EAggEC isolates from the patients had
      identical antibiotic sensitivity patterns and produced a toxin in Ussing chamber
      studies. Serotyping indicated that all the EAggEC from individuals with diarrhoea
      belonged to one or other of two serotypes. All water samples had high coliform
      counts and E. coli were cultured from the two open wells but not from the
      borewell. The evidence suggests that EAggEC was responsible for this outbreak of
      diarrhoea. EAggEC should be considered as a possible pathogen in unexplained
      diarrhoeal outbreaks in developing countries.

PMID- 9248209
TI  - Immunoreactivity of mycobacterial 70 kDa protein in different physico-chemical
      forms.
AB  - The immunoreactivity of 70 kDa culture filtrate protein of Mycobacterium
      tuberculosis H37 Ra has been examined as such and by increasing its
      hydrophobicity through its conjugation to stearic acid ester (70 kDa-FAester).
      The cell mediated immune responses produced by 70 kDa-FAester encapsulated in
      phosphatidylcholine (PC) liposomes were significantly higher particularly at the
      3rd week post immunization (wk p. im.) than that produced by the 70 kDa protein
      in PC liposomes, whereas humoral immune responses were non-significant. Further,
      these immune responses were comparable to that elicited by 70 kDa protein
      complexed with Freund's incomplete adjuvant (70 kDa-FIA). Results of this study
      suggest that changes in physicochemical nature of 70 kDa protein influences both
      the humoral and cellular immunoreactivity.

PMID- 9248210
TI  - Erythrocyte depletion of human umbilical cord blood using dextran sedimentation.
AB  - We report on the results of a study using high molecular weight dextran for
      depletion of red blood cells (RBCs) from cord blood. Our technique achieved
      efficient RBC depletion by sedimentation without a significant loss in
      haemopoietic stem cells. Cord blood units were fractionated for erythrocyte
      depletion by unit gravity sedimentation in 3 per cent high molecular weight
      dextran. Dextran sedimentation enabled recovery of more than 80 per cent of the
      total nucleated cells present and 100 per cent mononuclear cell (MNC) recovery as
      compared to unfractionated cord blood. A four-fold increase in the colony forming
      unit-granulocyte macrophage (CFU-GM) number per 2 x 10(5) cells was observed
      after dextran treatment suggesting that this step also resulted in the enrichment
      of stem cells.

PMID- 9248211
TI  - Morphological & morphometric studies on liver in rats subjected to repetitive
      heat stress.
AB  - Morphological and morphometric studies were conducted under light microscope on
      paraffin sections (H&E) of liver from controls and experimental rats subjected to
      repeated heat stress for 4 h/day, at 38 degrees +/- 0.5 degree C (relative
      humidity 65-82%) for 2-8 consecutive days. The morphometric variables were
      derived by intersection-point counting method, using simple square lattice test
      system A100. Twinning of liver cell plates and anisocytosis characterised
      morphological changes in rats exposed to heat twice. Following five heat
      exposures, rat liver showed ballooning degeneration of hepatocytes, associated
      with sinusoidal compression and loss of normal liver cell plate pattern. The
      degenerative changes in liver parenchyma were more pronounced in rats that
      underwent eight heat exposures. Despite hepatocytic degeneration, the numerical
      density of hepatocytes (Nvh) and the volume density of hepatocytes (Vvh)
      increased with the increase in number of heat exposures, indicating associated
      heat induced acceleration in hepatocytic proliferation. A successive fall, with
      increase in the number of heat exposures, in the sinusoidal length density (Jvs)
      and in the numerical density of Kupffer cells on area (Nak) revealed progressive
      damage to hepatic-vascular endothelium, which suggest an adverse effect on the
      immune status of the animals.

PMID- 9248212
TI  - Protective effect of zinc gluconate on chemically induced gastric ulcer.
AB  - This study was undertaken in rats to ascertain the role of zinc as an
      antiulcerogenic agent employing its more bioavailable gluconate derivative.
      Pretreatment with zinc gluconate 10 mg/kg body wt orally for three consecutive
      days, protected against alcohol induced gastric epithelial damage and also
      significantly prevented non-steroidal anti-inflammatory drugs (NSAID) induced
      gastric ulcer in rats. The enhanced levels of mucus, and hexosamine and decreased
      acid output in the gastric secretion of zinc treated rats, increased the gastric
      mucosal barrier. Studies on the mechanism of action suggested the involvement of 
      SH groups in producing gastric antisecretory effect. Thus, zinc gluconate at > >
      100 microM concentrations inhibited H(+)-ion transport which could be reversed by
      incorporating beta-mercaptoethanol in the secretory solution (luminal side). On
      the other hand, beta-mercaptoethanol added from the nutrient side showed no
      effect on the inhibition of H(+)-transport indicting that the implication of -SH
      groups may not be the sole factor. Zinc appeared to play a vital and multifaceted
      protective role in chemically induced gastric ulcer disorders.

PMID- 9248213
TI  - Assessment of the health effects of trichloroethylene.
AB  - The epidemiological studies performed thus far have presented only limited
      evidence for the carcinogenicity of trichloroethylene (TRI) to humans. However,
      these studies had drawbacks such as insufficient size of cohort, short
      observation period, and inadequate TRI exposure assessment; therefore, no
      concrete conclusion has been reached concerning TRI carcinogenicity to humans.
      Despite the limited epidemiological evidence as to the carcinogenicity of TRI,
      the International Agency for Research on Cancer (IARC) has changed the
      carcinogenicity classification of TRI from Group 3 (not classifiable as to
      carcinogenicity to humans) to Group 2A (probably carcinogenic to humans). In
      regard to the new classification by the IARC, the committee for occupational
      exposure limits of the Japan Society for Occupational Health has made a proposal
      that it is too early to classify the carcinogenicity of TRI as Group 2A and that
      it is proper to promote exposure control with the carcinogenicity being
      classified as 2B for the moment. There are species differences in TRI
      carcinogenicity, particularly between rats and mice. Although experimental
      studies have found no evidence that TRI induces liver cancer in rats, there is
      ample evidence that TRI promotes the development of liver cancer in mice,
      particularly in B6C3F1 mice. The carcinogenicity of TRI in this strain of mice
      may be based on an epigenetic mechanism rather on a genotoxic mechanism and the
      liver cancer may be induced only after TRI has been inhaled for a long period of
      time at concentrations high enough to cause cytotoxicity. Conversely, with no
      reports showing TRI-induced renal tumors in mice, the possibility has been
      suggested that this chemical induces such tumors in male rats. The species
      differences are mainly accounted for by differences in the metabolism of TRI
      between rats and mice. From a general survey of the literature, it can be
      concluded that TRI itself is not mutagenic. However, the conjugation of TRI with
      glutathione (GSH), a minor pathway of TRI metabolism, results in mutagenic
      metabolites in the kidney of rats. The acute toxicity of TRI is neurotoxicity
      based on its anesthetic action. An exposure to extremely high levels of TRI may
      cause the liver and kidney disorders. Repeated exposures to high levels of TRI
      may result in neuro-, hepato-, and/or nephrotoxicity. The main symptoms appearing
      after chronic exposure at low levels are neurological changes represented by
      subjective symptoms relating to central and autonomic nervous systems, or by a
      lowered conduction velocity of the nerves or a prolonged latency of the nerve
      responses. For the present, it is reasonable to use the neurological findings for
      establishing the reference values of TRI for both work and general environments.
      A value of 25 ppm (135 mg/m3) is proposed as a reference value for work
      environments, and 25-50 ppb (135-270 micrograms/m3) for the general environment
      (1/1,000 of the value for work environment).

PMID- 9248214
TI  - Pingueculae and pterygia in motorcycle policemen.
AB  - PURPOSE: Pinguecula and pterygium are speculated to be associated with corneal
      and conjunctival microtrauma from exposure to sunlight and/or dust. Occupational
      motorcycle driving is suspected to be associated with such exposure, so we
      investigated the prevalence of pingueculae and pterygia in motorcycle policemen.
      METHOD: Silt lamp finding obtained by periodic eye checkup for policemen (783
      motorcycle policemen and 207 control indoor workers) together with questionnaire
      were used for analyses. All pingueculae and pterygia were diagnosed under the
      definite criteria. RESULTS: The overall prevalence of pingueculae was 590/1,566
      eyes (37.7%) among motorcycle policemen against 127/414 eyes (30.6%) among the
      indoor workers (p < 0.01). Besides, with increasing age, the prevalence of
      pingueculae in the motorcycle policemen clearly exceeded those among the indoor
      controls. The prevalence of pterygia were very small to be analysed. CONCLUSION:
      Our results exhibited a significant relationship between occupational motorcycle
      driving and the prevalence of pingueculae. Thus it is strongly suggested that
      they should wear eye protection equipment (goggles, face shield and so on) to
      prevent from developing these lesions.

PMID- 9248215
TI  - Sitting posture and neck and shoulder muscle activities at different screen
      height settings of the visual display terminal.
AB  - The effects of the VDT screen height on working posture and electromyographic
      (EMG) activities of the neck and shoulder muscles were determined in 10 healthy
      subjects. The subjects performed a mouse-driven interactive task at the screen
      height settings of 80, 100 and 120 cm. Changes in body positions were measured by
      video image and frame analysis. Surface EMG recordings were done on the neck
      extensor muscle and the descending part of the trapezius muscle, both on the
      right side. The results of the postural analysis showed that at higher screen
      height settings, the neck became significantly more erect. The subjects also
      assumed a more backward-leaning trunk position at higher screen heights. The EMG
      activities of the neck and shoulder muscles were related to the neck angle and
      trunk inclination, respectively. A more flexed neck produced significantly higher
      neck extensor muscle activities. A backward-leaning trunk was also noted to
      decrease trapezius muscle activity in some subjects.

PMID- 9248216
TI  - Influence of local vibration on finger functions of forest workers.
AB  - We physically examined of forest workers in the northern part of Fukushima
      District, Japan. The main purpose of this study was to survey the state of finger
      functions, especially the differences between the functions of right and left
      fingers of forest workers. This physical examination was conducted in winter. The
      items of the physical examination were hand grip strength, finger skin
      temperature, vibration sensation threshold, nail pressure test of the finger.
      Subjects were classified into A and B groups on the base of the results of the
      physical examination. A group is normal or slight disorder, and B group is
      disorder or illness. Hand grip strength was measured five times at five-second
      intervals. The decrease ratio of the left hand grip strength was greater than
      that of the right hand grip strength. Although there were significant differences
      among each finger of A and B groups, there were no big differences in the skin
      temperatures of the fingers in each group. Vibration sensation threshold was
      measured for II, III and IV fingers. The vibration sensation threshold of the
      index finger was the most sensitive and that of IV finger was the least
      sensitive. The vibration sensation threshold of the right fingers was more
      sensitive than that of the left fingers. The reaction times of the nail pressure
      test of the right fingers were generally faster than those of the left fingers.
      Forestry workers in Japan become elderly. There are big differences among the
      physical reactions or strengths of elderly people. Standard values for the
      measuring items for ageing are needed.

PMID- 9248218
TI  - Quantitative time-course profiles of bronchoalveolar lavage cells following
      intratracheal instillation of lipopolysaccharide in mice.
AB  - This report shows the quantitative time-course profiles of transpulmonary
      migration of polymorphonuclear leukocytes (PMN) and the adhesive interaction of
      alveolar macrophages to the alveolar surface in response to intratracheally
      (i.t.) instilled endotoxin. Groups of mice received i.t. instillation of
      lipopolysaccharide (LPS), and free cells in the bronchoalveolar lavage (BAL)
      fluid were counted. PMN remaining in the lung tissue after the BAL procedure were
      also enumerated following enzymatic tissue digestion. Recovery of macrophages
      from the alveolar space by BAL was significantly decreased at 0.5 and 2 h post
      i.t. instillation and returned to the control value after 5 h, suggesting that
      alveolar macrophages became adhesive to the alveolar wall in response to LPS.
      Neither BAL nor lung tissue-associated PMN were increased until 0.5 h post i.t.
      instillation of LPS. The lung tissue-associated PMN peaked at 2 h, while the
      number of BAL PMN peaked at 5 h post instillation. Furthermore, although the
      number of BAL PMN remained at the maximum value even at 24 h post i.t.
      instillation of LPS, the lung tissue-associated PMN returned to the control level
      at this point. These results suggest that (1) the adhesive interaction of
      alveolar macrophages to the alveolar surface increased rapidly (< 0.5 h), (2)
      accumulation of PMN in the lung occurred later than the adhesion of alveolar
      macrophages (0.5 to 2 h) and (3) transpulmonary infiltration of PMN was completed
      within 24 h following i.t. instillation of LPS.

PMID- 9248217
TI  - A comparison of vibrotactile thresholds on the finger obtained with ISO type
      equipment and Japanese equipment.
AB  - A vibrotactile threshold measurement system that enables the thresholds at the
      fingertips to be determined more rapidly and precisely has been developed. This
      system was studied to assess the impact of various factors on the obtained
      values. An experiment using two different types of equipment was also conducted
      to assess the repeatability of measurement. One system was similar to that
      required by International Standard (System A), and the other system was of the
      currently used in Japan (System B). The subjects were nine males and one female,
      measurements were taken on three different days. This paper compares the
      structure of the equipment used internationally (ISO/CD13091) and the equipment
      typically used in Japan and the measurements of vibrotactile thresholds taken at
      a 125 Hz frequency using Systems A and B. The measurement method and conditions
      adopted were almost the same as those outlined in the ISO draft. The results of
      this experiment showed that there were some differences between the two systems.
      The vibrotactile thresholds measured using System B showed higher values than did
      those measured using System A. The results also indicated that equipment that
      satisfies ISO standards provides sufficient repeatability for use as a diagnostic
      aid. Also, this paper is shown the vibrotactile measurement equipment conditions
      must be considered when using vibrotactile threshold measurement equipment in
      Japan.

PMID- 9248219
TI  - Increases of thrombomodulin activity and antigen level on human umbilical vein
      endothelial cells treated with asbestos and man-made mineral fibers.
AB  - The potential influences of crocidolite asbestos fibers and man made mineral
      fibers (potassium titanate whisker and magnesium sulfate whisker) on a
      procoagulant system of human umbilical vein-endothelial cells (HUVECs) were
      investigated by measuring the activity and antigen level of thrombomodulin (TM)
      on the cell surface. Statistically significant increases in both the TM activity
      and TM antigen level were observed on HUVECs treated with crocidolite asbestos
      fibers for 48 h and 72 h compared to untreated cells at low concentrations of the
      fibers which showed no sign of a cytotoxic effect on the cells. An extensive
      increase in both the TM activity and TM antigen level was also observed on HUVECs
      treated with potassium titanate whisker or magnesium sulfate whisker for 48 h and
      72 h. A statistical analysis revealed that these fibers had almost the same
      effects on the increases in both TM activity and the TM antigen level of HUVECs
      treated with the fibers for 48 h and 72 h, but a treatment of magnesium sulfate
      whisker at more than 1.25 micrograms/ml for 24 h was slightly more effective in
      increasing TM activity on HUVECs compared to other fibers (p < 0.05). The
      [3H]leucine incorporation in HUVECs increased when the cells were treated with
      crocidolite asbestos or man-made mineral fibers (MMMFs), indicating that the
      increases in TM activity and the TM antigen level on HUVECs directly exposed to
      those fibers may not reflect the sole induction of anticoagulant activities, but
      the general cell damage induced by the fibers.

PMID- 9248220
TI  - Genotoxic effects in workers exposed to benzene: with special reference to
      exposure biomarkers and confounding factors.
AB  - The aim of the study was to establish a correlation between biomarkers of
      exposure and cytogenetic test results in workers occupationally exposed to
      benzene and toluene, with special reference to confounding factors influencing
      the outcome of the cytogenetic test. The incidence of structural chromosome
      aberrations and sister chromatid exchanges was studied in the peripheral blood
      lymphocytes cell genome of 49 female shoe-makers, mean age 38 years, mean length
      of occupational exposure 17 years and in a group of 27 well-matched controls.
      Workers were exposed to concentrations of benzene up to 15 ppm and of toluene up
      to 50 ppm. The presence of benzene and toluene in the workers' blood samples, and
      the presence of phenol in pre- and post-shift urine were considered proof of
      occupational exposure. Chromosomal aberration analysis revealed a significant
      increase in dicentric incidence in the exposed group compared to the controls (P
      = 0.004). However, significant correlation between cytogenetic test results and
      the exposure biomarkers was not established. On the contrary, correlation between
      the cytogenetic test results and data on confounding factors (e.g. age and
      alcohol consumption), was marked. The major point raised by this study is the
      influence of confounding factors on the cytogenetic test outcome. This imposes
      the need for caution in the interpretation of cytogenetic test results, and
      ultimately in the estimation of individual genotoxicity risk related to low level
      benzene exposure.

PMID- 9248221
TI  - A study on the beryllium lymphocyte transformation test and the beryllium levels
      in working environment.
AB  - The relationship between airborne concentration of beryllium in the working
      environment and workers' beryllium lymphocyte transformation test (Be-LTT) values
      was examined based on data obtained from a four-year survey (1992-1995) conducted
      at beryllium-copper alloy manufacturing factories. This study showed that the T
      cells of workers continuously exposed to beryllium of more than 0.01 microgram/m3
      could be activated and that the cell-mediated immune response of workers could be
      promoted. On the other hand, the Be-LTT of workers exposed to beryllium levels of
      less than 0.01 microgram/m3 was shown to be unaffected by beryllium. These
      findings suggest that beryllium sensitization is not manifested when level of
      beryllium in working environment are less than 0.01 microgram/m3. Therefore, in
      such cases workers do not develop Chronic beryllium disease (CBD). We concluded
      that the Be-LTT can be applied as a medical indicator to detect the development
      of CBD.

PMID- 9248222
TI  - Silica-induced oxygen radical generation in alveolar macrophage.
AB  - Silica is a well-known occupational fibrogenic agent and its primary target cell
      is alveolar macrophage. Particle-stimulated macrophages are believed to release
      various mediator which can regulate the inflammation as well as pulmonary
      fibrosis. Even though oxygen radicals play the major role among these mediators,
      the mechanisms concerning the stimulation of alveolar macrophages are not clear
      yet. The present study was carried out to investigate the signal transduction
      pathway on oxygen radical generation in silica-stimulated alveolar macrophages.
      Silica induced oxygen radical generation in a dose-response pattern.
      Extracellular calcium depletion, calcium channel blockers, and calcium release
      blocker decreased the effect of silica on oxygen radical generation. Silica
      increased intracellular calcium through the influx of calcium through the calcium
      channel and the calcium release from the intracellular calcium store. To know the
      role of protein kinase C (PKC), phospholipase C (PLC), and protein tyrosine
      kinase (PTK) in silica-induced oxygen radical generation, we pretreated alveolar
      macrophages with inhibitors of these enzymes. Inhibitors of PKC (sphingosine and
      staurosporine), PLC (neomycin and U-73122), and PTK (genistein and erbstatin)
      suppressed the silica-induced oxygen radical generation. Silica increased the PLC
      activity at the concentration of 5 mg/ml. The inhibitors of PTK and PLC
      suppressed the action of silica on the PLC activity. From these results, we
      suggest that silica induces oxygen radical generation through PTK, PLC, and PKC
      in alveolar macrophages.

PMID- 9248223
TI  - Citrate uptake by isolated rat renal brush border membrane vesicles in cadmium
      intoxicated rats.
AB  - Epidemiological Studies have reported that the formation of renal stones is often
      observed in workers exposed to cadmium (Cd). Citrate is known to be a protective
      factor against renal stone formation. We previously reported that direct exposure
      to high-level cadmium impaired the citrate uptake by the brush border membrane
      vesicles (BBMV), which may mean that the formation of renal stones from exposure
      to Cd could be prevented. In the present study, to clarify the mechanism of Cd
      induced renal stone formation, the characteristics of BBMV-induced citrate uptake
      were determined in Cd-intoxicated rats. Cd intoxication was induced by daily
      subcutaneous injections of CdCl2 at a dose of 2 mg Cd/kg body wt per day for 17
      to 20 days. The BBMV were prepared by the divalent cation precipitation method.
      Citrate uptake was measured by the Millipore rapid membrane filtration technique.
      The citrate uptake per mg protein was not significantly different between the two
      groups. The volume of BBMV was significantly reduced (50%) in Cd-intoxicated rats
      compared with that of control rats. Percentages of the equilibrium value were
      also significantly inhibited in Cd-intoxicated rats.

PMID- 9248224
TI  - Size-selective sampling of oil mist in air and subjective symptoms among machine
      workers.
AB  - Oil mists at an automobile factory were measured size-selectively. Furthermore,
      subjective symptoms were surveyed through the distribution of a questionnaire.
      The measured levels of respirable-size, 2-10 micrometer oil mists at 3 selected
      workshops ranged 0.04-0.09 mg/m3 for the lower exposed group (17 men), 0.10-0.18
      mg/m3 for the higher exposed group (16 men) to water-insoluble oil, and 0.08-0.29
      mg/m3 for the higher exposed group (19 men) to water-soluble oil. The higher the
      level of exposure to respirable-size particulates, the more workers complained of
      dissatisfaction with air quality. As to the subjective symptoms, the "yes" rate
      for "irritated nose" and "sneezing" showed significant differences among the
      unexposed, lower exposed, and higher exposed groups. Workers using water-soluble
      oil complained of "uncomfortable smell" more than those who used water-insoluble
      oil. The results of this study suggested that it is necessary to measure the
      levels of oil mists size-selectively.

PMID- 9248225
TI  - Quantitative determination of urinary metabolites of o-dichlorobenzene using a
      gas chromatograph.
AB  - o-Dichlorobenzene (o-DCB) is used as an organic solvent, as a chemical
      intermediate, and as a heat transfer medium. In humans, o-DCB is metabolized to
      2,3- and 3,4-dichlorophenols, and 3,4- and 4,5-dichlorocatechols, and these
      metabolites are eliminated via the kidneys. In this study, we tried to determine
      the concentrations of urinary 2,3- and 3,4-dichlorophenols using a gas
      chromatograph (GC). When control urine specimens were spiked at concentrations of
      10, 20 and 40 mg/l, the mean recovery rates of 2,3- and 3,4-dichlorophenols were
      98.3 to 101.9% (CV = 4.0 to 4.8%) and 100.6 to 105.4% (CV = 2.5 to 7.0%),
      respectively. Next, urine samples collected from ten male workers exposed to o
      DCB were analyzed. The concentrations of urinary 2,3- and 3,4-dichlorophenols
      determined by the GC method closely agreed with those by the HPLC method, which
      we had developed in a previous study, and these metabolite concentrations were
      linearly correlated to the 8-h TWA values of o-DCB in the range of 0.1 to 2.3
      ppm. Consequently, the GC method can be used for biological monitoring of o-DCB,
      though it is necessary that the linear relation is confirmed in a higher range of
      exposure.

PMID- 9248227
TI  - Preparation and characteristics of standard reference samples of fibrous minerals
      for biological experiments.
AB  - Standard reference samples of fibrous minerals to be used for in vitro and in
      vivo (injection) biological experiments were prepared. Ten samples were selected
      from among the fibrous minerals currently used in industry: man-made mineral
      fibers (MMMF); glass wool (GW1), rock wool (RW1), micro glass fiber (MG1),
      refractory ceramic fibers (RF1, RF2), and mullite fibers (RF3), whiskers;
      potassium titanate (PT1), silicon carbide (SC1) and rutile (TlO2)(TO1), and a
      natural fibrous mineral; wollastonite (WO1). The MMMF samples were prepared by
      using the size-selective press method. The whisker samples and WO1 were all
      commercial products. The prepared samples were examined by X-ray diffraction and
      X-ray fluorescence analyses, and no impurities were identified in any of the
      samples at a level of 1%, although WO1 was found to have about 5% calcite and a
      trace amount of quartz (< 1%). The fiber sizes were measured by TEM. The
      geometric-mean length (micron), width (micron) and SD (in parenthesis) are: GW1
      20.0 (2.58), 0.88 (3.10); RW1 16.5 (2.51), 1.80 (2.32); MG1 3.0 (2.22), 0.24
      (2.35); RF1 12.0 (2.36), 0.77 (2.53); RF2 11.0 (1.96), 1.10 (2.00); RF3 11.0
      (1.75), 2.40 (1.37); PT1 6.0 (2.04), 0.35 (1.51); SC1 6.40 (2.45), 0.30 (1.58);
      TO1 2.1 (2.00), 0.14 (1.53); WO1 10.5 (2.03), 1.00 (1.72). We concluded that
      these prepared fiber samples can be safely used for biological experiments.
      Sample sets containing about one gram of each sample known as JFM standard
      reference samples are provided by the Japan Fibrous Material Research Association
      (JFMRA).

PMID- 9248229
TI  - Employee stress status during the past decade (1982-1992) based on a nation-wide
      survey conducted by the Ministry of Labour in Japan.
AB  - In this paper we will report the results of nation-wide surveys on employee
      health conducted and published by the Ministry of Labour in 1982, 1987, and 1992.
      The subjects were approximately 20,000 employees in 1982, approximately 15,000 in
      1987, and approximately 16,000 in 1992, from throughout Japan. Using the results
      of the surveys, we will show trends in the status of employee work-related
      stress, as well as trends in means of relaxation over the past decade. The
      percentage of employees with work-related stress among all subjects gradually
      increased as follows: 50.6% in 1982, 55.0% in 1987, and 57.3% in 1992. The
      percentage of employees with work-related stress increased remarkably from 1982
      through 1992 among the following groups: the 50-59 age group in males; employees
      in the electricity, gas, heat and water-supply industries; those in the real
      estate industry; administrative and managerial workers; employees of large
      establishments with more than 5,000 employees; and employees performing shift
      work involving no night duty. The problem of "human relationships in the
      workplace" was associated with the increasing stress levels among 50-59-year-old
      males, 40-49-year-old females, employees of large establishments with more than
      5,000 employees, those in the real estate industry, and service workers. In terms
      of means of relaxing to relieve fatigue and stress, employees tended to engage in
      active pursuits such as "eating out and shopping" and "driving and traveling"
      over the past decade. In 1992, on the other hand, 22.0% of males and 5.9% of
      females selected "smoking" as a means of relaxation. This shows the need for
      stress management in the workplace in order to prevent health problems related to
      smoking.

PMID- 9248228
TI  - Development of a new aerosol generating cell with an ultrasonic nebulizer.
AB  - A new efficient cell was developed to generate a large quantity of aerosol using
      an ultrasonic nebulizer. The currently used conventional pail-type cell cannot
      generate such a large quantity of aerosol because a large portion of the mist is
      lost by agglomeration and subsequent liquefaction onto the cell wall and liquid
      surface. The newly developed cell is a chimney-type cell characterized by the
      attachment of a vertical cylinder at its center and a partition to separate the
      cell into upper and lower compartments, each of which is supplied with a carrier
      air flow. The mist emanating from the fluid surface is carried upward through the
      vertical cylinder by a laminar primary airflow. The secondary airflow served to
      sheath the primary airflow containing the mist and to prevent the impact and
      adhesion of the mist on the surrounding wall. The nebulizing rate of TiO2
      suspension was found to be three times higher with the chimney-type than with the
      pail-type. No differences were found between the two types in terms of particle
      diameters, particle size distribution, and the electron microscopic images of the
      aerosol. It was concluded that a commercially available ultrasonic nebulizer
      equipped with the chimney-type cell allowed generation of a large quantity of
      aerosol for use in inhalation animal experiments.

PMID- 9248226
TI  - Evaluation of an activated carbon felt passive sampler in monitoring organic
      vapors.
AB  - Using an activated carbon felt (ACF, KF-1600), the applicability of an ACF
      passive sampler in monitoring organic vapors was evaluated. The evaluated results
      of the ACF passive sampler were compared with those of a 3 M (Model 3500) passive
      sampler. At low-humidity condition (8 +/- 3% RH), the sampling rates of the ACF
      passive sampler for volatile organic vapors were within the range of +/-25% from
      the results of a charcoal tube, which was the reference method recommended by
      NIOSH. However, at high humidity condition (90 +/- 5% RH), even though the
      sampling rates for toluene, MIBK, and PCE were within the range of +/-25%, the
      sampling rates of ACF sampler for n-hexane and MEK decreased steeply with time
      after being high at the beginning of the exposure time. Under this condition, the
      sampling rate of the 3 M passive sampler for MEK was also high at the beginning
      of the exposure time. In case of the ACF passive sampler, the sampling rates of
      the relatively strong adsorbates such as toluene, MIBK, and PCE were much less
      affected by humidity than those of n-hexane and MEK which were weak adsorbates.

PMID- 9248230
TI  - Kidney disease: jade, dialysis or transplantation?

PMID- 9248231
TI  - An epidemic of hyperthyroidism following salt iodination in Lebanon.
AB  - Salt iodination, in Lebanon, started partially in late 1992, and was implemented
      in a uniform manner by January 1995. Following salt iodination, an epidemic of
      iodine-induced thyrotoxicosis occurred, as noted by the author, in his private
      clinic. The number of thyrotoxic patients increased sharply by 2 to 6 folds, and
      the yearly incidence rose from a baseline of 0.02% up to 0.07%. The younger
      patients have predominantly Graves' disease (32% of the cases), while 17% have
      solitary thyroid nodules, and 44% of the cases were elderly subjects with
      multinodular goiter. The pathogenesis and possible causes of this epidemic are
      discussed.

PMID- 9248232
TI  - The accuracy of carotid duplex scanning in the diagnosis of 70% internal carotid
      artery stenosis: evaluation of new duplex criteria.

PMID- 9248233
TI  - Spontaneous resolution of cholelithiasis in an infant.
AB  - Cholelithiasis is an extremely unusual finding in infancy. Hemolytic disease,
      bile duct abnormalities, intestinal malabsorption have been implicated. Recently,
      an association of prematurity, bronchopulmonary dysplasia, total parenteral
      nutrition and furosemide has been reported. Rarely, sonographic discovery of
      idiopathic gallstones and their subsequent spontaneous disappearance has been
      reported. We report a case of an 11-week-old infant whose initial sonogram
      displayed evidence of true gallstone, that later showed resolution on follow-up
      examinations. In the absence of clinical or imaging evidence of biliary tract
      disease, we suggest an initial conservative management and follow-up sonograms.

PMID- 9248234
TI  - A century of blood pressure recording.

PMID- 9248235
TI  - In memoriam Rosa Lee Nemir (1905-1992).

PMID- 9248236
TI  - Weapon carrying and substance abuse among college students.
AB  - Results from administering the Core Alcohol and Drug Survey on 61 US campuses
      during the 1994/95 academic year were analyzed to assess weapon carrying among
      college students. Seven percent of the 26,225 students (11.1% of the men and 4.3%
      of the women) responded that they had carried weapons (gun, knife, etc) during
      the last 30 days. A comparison with a matched sample of nonweapon carriers
      revealed that a greater percentage of the armed than the unarmed students had
      experienced harassment, violence, and threats of violence, and that they felt
      less safe on their campuses. The weapon-carrying men consumed significantly more
      alcohol than their unarmed counterparts, and a higher percentage reported binge
      drinking, use of other drugs, and adverse consequences from substance abuse.
      Differences between armed and unarmed female students were not as clearly
      consistent in terms of substance abuse and consequences.

PMID- 9248237
TI  - College student reasoning about illness and psychological concepts.
AB  - Cognitive-developmental reasoning level in dealing with illness and psychological
      concepts, experiences with physical illness and psychological difficulties, locus
      of control orientation, and demographic variables were assessed in 101 college
      students. On average, the students' reasoning about both illness and
      psychological concepts was in transition from concrete to formal operational
      levels. However, the students' cognitive-developmental reasoning levels varied
      across illness and psychological domains and across some concepts within each
      domain. The reasoning levels for illness concepts were found to be significantly
      more advanced than the reasoning levels for psychological concepts. Female
      students' reasoning scores for psychological concepts were significantly higher
      than those of male students. Descriptive information for locus of control
      orientation, experience with illness, and psychological problems, as well as
      associations between variables and comparisons of means, are provided. The
      study's implications for college health providers in terms of treatment,
      prevention, and educational strategies are discussed.

PMID- 9248238
TI  - Traumatic injuries among university students in Finland.
AB  - A questionnaire dealing with the incidence of traumatic injuries was sent to
      1,000 randomly selected 3rd-year university students in Finland; 617 students
      responded adequately. Of those, 177 (28.7%) reported a combined total of 281
      accidents and 323 separate injuries requiring medical or dental treatment during
      the preceding 3 years. The accidents resulted in 1,061 days of official sick
      leave, and one third of the accidents caused permanent sequelae to the affected
      students. Almost half of all accidents had been sustained during sports
      activities and 14% in traffic. Only 0.5% of the accidents were classified as
      having occurred in the university environment or during activities directly
      related to studies. Alcohol was involved in 10.1% of the accidents; 45% of the
      injuries affected the lower extremities, and 22% the upper extremities. Most of
      the injuries were related to the students' active lifestyles and keen interest in
      sports.

PMID- 9248240
TI  - The cold clinic: a collaborative nursing effort to benefit students.
AB  - Collaboration between a nurse educator and nurse administrator paired beginning
      baccalaureate nursing students and the university health center's self-care cold
      clinic to benefit all involved in the project. Nursing students assisted clients
      through the cold clinic's five stations, establishing relationships and
      practicing communication and assessment skills. The health center benefited from
      exposure to the new techniques brought to the experience by nursing students,
      clients benefited from having a personal care provider during their cold-clinic
      experience, and nursing students benefited from being able to practice nursing
      skills that emphasized critical thinking over high-tech skills as they worked
      with clients of their own age. In sum, students were educated, wellness was
      promoted, and self-care behavior was enhanced.

PMID- 9248241
TI  - Factors predisposing to postoperative complications related to wisdom tooth
      surgery among university students.
AB  - In a retrospective study among 550 Helsinki University students 20 to 30 years
      old, factors predisposing to postoperative complications from removal of lower
      jaw wisdom teeth were evaluated. Patient records and panoramic tomograms covering
      the period from 1990 to 1993 were examined; 50 patients (9.1%) had postoperative
      complications after removal of a wisdom tooth. The most common complications were
      alveolar osteitis (2.9%), postoperative infection (2.6%), postoperative bleeding
      (1.5%), and dysesthesia of the lower lip or tongue (1.1%). Factors associated
      with increased postoperative complications were mesiohorizontal position of the
      tooth, deep impaction of the tooth, and use of oral contraceptives. Before
      patients undergo surgery for removal of wisdom teeth, those who use oral
      contraceptives or have difficult tooth impactions should be informed about the
      increased possibility of postoperative complications.

PMID- 9248239
TI  - Identifying the social contexts of effective sex refusal.
AB  - A factorial survey was conducted to identify social situations that inhibit or
      promote college students' sex-refusal skills. Respondents evaluated five
      different situations in which sexual intercourse might occur and ranked each
      according to how certain the respondent would be to refuse to have sexual
      intercourse in that context. Regression analysis of the survey data showed that
      knowing the other person well, being with one's boyfriend or girlfriend, having
      condoms available, wanting to have sex, and both persons' wanting to have sex
      reduced the probability of refusal. On the other hand, having no condoms and the
      presence of drugs in the situation increased the probability the individual would
      refuse to have sex. In addition, men, individuals with previous sexual
      experience, and drinkers displayed diminished ability to refuse sex. However, the
      lack of condoms, when combined with these three respondent characteristics, acted
      to increase the ability to refuse sex.

PMID- 9248242
TI  - Student mental health and funding constraints: a delicate balance.
AB  - A wide range of serious psychiatric disorders that would be progressive if
      untreated was observed during the first 9 months of a 1-year psychotherapy
      fellowship at the student health center of a major New England university. This
      finding underscores the cost benefits, in both human and financial terms, of
      having a multidisciplinary mental health center staff on campus to provide
      timely, intensive, and comprehensive interventions.

PMID- 9248243
TI  - Checking the small things.

PMID- 9248244
TI  - AOA/NHBPEP partnership turns 20.

PMID- 9248245
TI  - Managed care.

PMID- 9248246
TI  - Bifocals and myopia.

PMID- 9248247
TI  - Corneal astigmatism in native American children.

PMID- 9248248
TI  - Current perspectives on nonarteritic anterior ischemic optic neuropathy.
AB  - BACKGROUND: The traditional view of nonarteritic anterior ischemic optic
      neuropathy (NAION) has been challenged. Progressive forms of the disease and
      spontaneous improvements in vision have been reported with increasing frequency.
      The pathogenesis of the disease has been refined. Treatment in the form of optic
      nerve sheath decompression has been advocated and dismissed by a major study.
      METHODS: The pathogenesis, presentation, risk factors, and associated conditions,
      differential diagnosis, and management of NAION are reviewed. RESULTS: NAION is
      currently considered an untreatable, ischemic disorder of the optic nerve head.
      In most cases, it results from a drop in optic nerve head perfusion pressure,
      below a critical level. No treatment is available to restore perfusion before
      loss of vision and visual field takes place. CONCLUSIONS: Despite changes in the
      reported natural history and pathogenesis of NAION, there is still no available
      treatment. Management involves reduction of risk factors to prevent development
      of the disease and differentiating it from the arteritic type.

PMID- 9248249
TI  - Distribution of astigmatism among Sioux Indians in South Dakota.
AB  - BACKGROUND: Previous studies have reported a greater prevalence of high
      astigmatism and vision disorders among Native Americans than occurs in the
      general U.S. population. The majority of these studies, however, have focused on
      Native American schoolchildren. This study assessed the distribution of
      astigmatism in a general clinic population at the Rosebud Indian Reservation in
      South Dakota. METHODS: From examination of 174 patients, demographic information,
      visual acuities, refractive error, binocular vision status, and eye health were
      recorded. RESULTS: The data showed more high astigmatism than would be expected
      in a general U.S. population. Three or more diopters of astigmatism were found in
      9.2% of the right eyes and 10.8% of the left eyes in the study population. High
      astigmatism was noted less frequently among those ages 40 years and older (3.3%
      right eyes, 6.3% left eyes). Most of the astigmatism was with-the-rule, but a
      shift toward against-the-rule and oblique astigmatism was found in older
      individuals. No significant gender differences were noted. CONCLUSIONS: The
      results suggest an ethnic difference in astigmatism and emphasize thee need for
      continued and expanded vision services for Native American populations.

PMID- 9248250
TI  - Tangential penlight angle estimation.
AB  - BACKGROUND: A variation of the penlight shadow procedure, using tangential
      corneal illumination, was compared with the van Herick biomicroscopy technique
      for estimating the anterior chamber. The purpose was to determine if tangential
      penlight illumination affords the practitioner an additional, clinically valid
      means of estimating patency of the anterior chamber angle. METHODS: Sixty-two
      subjects (24 males, 38 females) were evaluated with both procedures. For each
      subject, the temporal anterior chamber angles were estimated on the basis of the
      degree of nasal brightness via sclerotic scatter after temporal tangential
      corneal illumination. Comparisons were made with temporal angle estimation using
      the van Herick biomicroscopy technique. RESULTS: Compared with the van Herick
      procedure, the tangential corneal illumination technique had a sensitivity of
      93.8% in the measurement of open angles, with a specificity of 83.3%. The results
      were statistically significant at p < 0.001. CONCLUSIONS: The results suggest
      that the tangential corneal illumination technique provides a viable alternative
      to angle estimation using the biomicroscope. The procedure compared favorably
      with previous assessments of the standard penlight shadow test. Although limited
      in certain aspects, the speed and ease of the procedure make it a useful
      diagnostic tool in situations in which conventional testing is difficult or
      impossible to accomplish.

PMID- 9248251
TI  - Men and women in optometry. II. Attitudes toward career and family.
AB  - BACKGROUND: Optometry has experienced a dramatic upward shift in the percentage
      of women entering the profession during the past 20 years. Our survey assessed
      the mechanisms for sustaining balance in professional and personal roles used by
      women optometrists and how these mechanisms may differ from those of their male
      colleagues. METHODS: A survey questionnaire was mailed to a large nationwide
      random sample of optometrists, composed of equal numbers of men and women.
      RESULTS: Data were analyzed from 353 men and 358 women; margin of error was +4%.
      Most of the respondents indicated they derived personal satisfaction from their
      career. A majority of both groups did not indicate that lack of time for their
      career was a source of frustration. However, significantly more women than men
      indicated some frustration in pursuing those activities that lead to career
      advancement. There were significant differences in response patterns of men and
      women about the effect of family, child care, and household work on their
      careers. CONCLUSIONS: Both men and women optometrists are satisfied with their
      careers and neither group feels compelled to choose between career and family.
      Optometrists do not fit into one pattern, but instead make individualized career
      choices on the basis of needs.

PMID- 9248252
TI  - Corneal topography after excimer laser photorefractive keratectomy for myopia.
AB  - BACKGROUND: This study was performed to assess and correlate the changes in
      central corneal power with the changes in manifest refraction after myopic
      photorefractive keratectomy (PRK) and to measure ablation zone centration.
      METHODS: Fourteen patients had computerized videokeratography and manifest
      refraction performed preoperatively, and than 1, 2, 3, 4, 6, and 12 months after
      photorefractive keratectomy. RESULTS: There was a significant association (r = 
      0.9; p < 0.0001) between changes in manifest refraction and changes in central
      corneal power at the 12-month postoperative examination; however, a mean
      difference of 1.1 D was seen between the two readings. The mean decentration of
      the ablation zone was 0.47 +/- 0.26 mm (range, 0.08 to 1.05 mm: 0 to 0.49 mm, six
      patients; 0.50 to 0.99 mm, seven patients; and 1.00 to 1.50 mm, one patient).
      CONCLUSIONS: Corneal power-as measured by videokeratography-is not an accurate
      predictor of manifest refraction, although the two parameters did demonstrate
      good correlation. Centration of ablations was comparable to previous studies.

PMID- 9248253
TI  - Spectacle/loupe telescope designed for reading music.
AB  - BACKGROUND: The optical needs of most low-vision patients can be satisfied with
      one or more of a large array of prefabricated, off-the-shelf, handheld or
      spectacle-mounted devices. When these devices do not provide the expected or
      desired results, a practitioner has the opportunity to design a custom-made
      device to satisfy the vision demands of the patient. CASE REPORT: A patient with
      a history of having tried several devices to see his music while playing the
      violin was examined and a simple, inexpensive. Galilean telescopic device was
      formulated, designed, and constructed. The objective was to create a telescope
      that would provide adequate magnification with a wider field of view than was
      available with prefabricated devices. The components needed to generate the
      required magnification were determined using basic telescope design concepts and
      equations. CONCLUSIONS: For patients with intermediate and/or distance symptoms
      testing with a telescope is an important part of the low-vision evaluation. Field
      of view, expense, and the time required to obtain the device are important
      considerations in deciding what to prescribe. The pathology involved, task
      demands, time since onset of decreased acuity, and personality of the patient
      will dictate, to a large degree, the acceptance of the device.

PMID- 9248255
TI  - Does obesity increase the risk for cataracts?

PMID- 9248254
TI  - Zinc: the missing link?

PMID- 9248256
TI  - Ubiquinone--the everywhere nutrient.

PMID- 9248257
TI  - [Development of a high resolution beta camera].
AB  - We have developed and tested a high resolution beta camera. The beta camera
      consists of thin CaF2(Eu) scintillator, tapered fiber optics plate, position
      sensitive photomultiplier tube (PSPMT). The output of the PSPMT is fed to
      position calculation circuit and accumulated in the memory. The data in the
      memory is fed to personal computer for display and analysis. We have developed
      two types of beta cameras. One is 20 mm diameter field of view (FOV) camera, and
      the other is 10 mm diameter camera. Intrinsic spatial resolutions were 0.8 mm
      FWHM and 0.5 mm FWHM for 20 mm and 10 mm FOV camera, respectively. We confirmed
      that developed beta cameras may overcome the limitation of the resolution of the
      PET camera.

PMID- 9248258
TI  - [Prediction of the myocardial contractility improvement on early stage after the
      revascularization using low-dose dobutamine stress 99mTc-MIBI gated SPECT].
AB  - For prediction of recovery of LV contractility, 99mTc-MIBI gated SPECT at rest
      and that with dobutamine (DOB) loading were performed in 15 patients with
      myocardial infarction (MI). Regional % uptake (regionalx100/maximal count), %
      wall thickening [%WT; (ES-ED)x100/ED maximal count], and delta %WT (%WT at DOB
      stress-%WT at rest) were calculated for each of 8 segments (seg.), including 34
      MI out of total 120 seg., which derived from short axis LV count profile. These
      34 seg. were divided into two groups, recontractile (18 seg.) and non
      recontractile (16 seg.), whether improvement of the wall motion following the
      intervention (3-5 months) was observed by echocardiography. In the result, there
      were 7 recontractile seg. in 8 seg. with mildly reduced perfusion (> or = normal
      mean % uptake-2 S.D.), and there were 11 recontractile seg. in 26 seg. with
      severe reduced perfusion (< normal mean % uptake-2 S.D.). Moreover, in segments
      with severely reduced perfusion, there was no significant % uptake difference
      between recontractile and non-recontractile seg. However, delta %WT of
      recontractile group (11.1 +/- 4.8%) was significantly higher than that of non
      recontractile group (5.7 +/- 2.9%) (p < 0.01). In conclusion, although the
      improvement of contractility on early stage after the revascularization was
      sometimes underestimated with only perfusion (% uptake), myocardial DOB response
      of %WT which were obtained by gated SPECT with MIBI would avoid the
      underestimation.

PMID- 9248259
TI  - [A limitation of the split-dose method for evaluating rCBF changes using 99mTc
      ECD and SPECT].
AB  - The purpose of the study is to validate the split-dose method corrected with dose
      ratio of 99mTc-ECD for brain perfusion scan. A dose of 600 MBq of 99mTc-ECD was
      divided into two with various dose ratios from 1:1 to 1:4, and injected to eleven
      patients with various cerebral diseases. A lesser dose of 99mTc-ECD was injected
      under a control state for the first SPECT scan, and 15 min SPECT scan was
      performed 10 min after injection with a triple-head high resolution gamma camera.
      After the scan, the other dose of 99mTc-ECD was injected under the same control
      state and the second SPECT scan was performed as same as above. A ratio of the
      activity of the first scan to the net activity of the second scan corrected by
      dose ratio, defined as K, was measured in brain regions of each subject. Expected
      value of K was 1, but the value was distributed with large variations in each
      subject. The mean % error of the K value was 10.4 +/- 4.9%. Hence it is
      considered that activity changes by more than 20% from the control values should
      be required to detect a significant rCBF change in an activation SPECT study.
      Then, we proposed a new method in which the activity of both two SPECT scans was
      normalized by cerebellar or occipital activity and compared. The ratio obtained
      by the proposed method came closer to 1 with less variations and with less mean %
      error in comparison with those of K value obtained by the dose-correction method.
      Although the proposed method has a limitation in the use of an activation study
      loaded with Diamox, it may be useful to evaluate an alteration of rCBF in the
      study such as postural testing or finger-moving test.

PMID- 9248260
TI  - [Cost effectiveness analysis of FDG-PET in the differential diagnosis and staging
      of lung cancer in Japan].
AB  - Several studies have shown that FDG-PET is more accurate than CT for the
      differential diagnosis and for the staging of lung cancer. We have analyzed
      potential effect of FDG-PET on the medical cost for the management of patients
      suspected of lung cancer. In the differential diagnosis, chest CT plus FDG-PET
      protocol reduced the number of bronchofiberscope (BFS) and biopsy by one fourth
      of that in the conventional protocol using CT alone. PET protocol reduced
      unnecessary examinations for the patients of benign disease, however, it
      increased the total cost of examinations by 25% due to the higher cost of PET
      than that of BFS and biopsy in Japan. In the staging of lung cancer, PET protocol
      improved accuracy of staging, reduced unnecessary surgery by 67%, and showed a
      saving of the cost of examination by 5%, and the total medical cost by 2.5%
      compared to that in the conventional protocol using CT, brain MRI, and bone scan.
      CONCLUSION: Use of FDG-PET for the staging may contribute to the improvement of
      patient management of lung cancer patients also to the saving of the medical
      cost.

PMID- 9248261
TI  - [The possibility of evaluation on inflammatory change at respiratory tract in
      chronic bronchial asthma using 67Ga scintigraphy].
AB  - 67Ga scintigraphy was performed in 17 patients with chronic bronchial asthma to
      grasp the inflammatory change of respiratory tract. On 67Ga scintigraphy,
      abnormal accumulations were detected on lung fields in 6 cases (35.3%) of 17
      cases. In 5 cases of these 6 cases, the defect areas which were pointed out on
      81mKr ventilation scintigraphy were matched to the abnormal accumulation areas
      which were pointed out on 67Ga scintigraphy. In dynamics, the abnormal
      accumulation areas which were pointed out on 67Ga scintigraphy were matched to
      the defect areas which had been at all times pointed out on 81mKr ventilation
      scintigraphy. 67Ga scintigraphy was expected to be one of index to grasp the
      inflammatory change of respiratory tract in patients with chronic bronchial
      asthma.

PMID- 9248262
TI  - [Reproducibility of regional cerebral blood flow measurement at rest with
      autoradiography method using 123I-IMP and SPECT].
AB  - Reproducibility of regional cerebral blood flow (rCBF) values obtained by the
      autoradiography (ARG) method with one SPECT scan and one point arterial blood
      sampling at 10 min after 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion was
      evaluated. The variation in the cross calibration factor between SPECT counts and
      well-type scintillation counts remained 2.2% for 13 months. The error in rCBF by
      sampling time difference was less than 3% when sampling time was within 10 min +/
      30 sec after infusion. There was a favorable correlation between the rCBF values
      in two separate resting scans measured by the ARG method in 10 patients (r =
      0.907). And the mean ratio of rCBF values by the second study to those by the
      first study in the cerebellum and cerebral lobes in 10 patients was 0.989 +/-
      0.056 (mean +/- SD). There was no significant difference in rCBF values between
      two separate studies. Reproducibility of rCBF with the ARG method was proved to
      be good. The ARG method was thought to be useful for the assessment of treatment
      effects and clinical courses.

PMID- 9248263
TI  - [Prophylactic effect of black tea extract as gargle against influenza].
AB  - We examined whether gargling with black tea prevents influenza infection. Tests
      were carried out during a five month period (October 1992 to March 1993). The
      control group that followed their normal daily routine, whereas the test group
      that gargled with 0.5 w/v% black tea extract twice daily (at 8 a.m. and 5 p.m.).
      Influenza viruses were isolated from influenza patients and an antigen analysis
      was carried out. As a result, two strains of influenza A viruses (H3N2) and ten
      strains of B virus were detected. An HI test was done using paired sera of the
      control group and the test group. The HI titers raised a four fold or greater in
      48.8% (61/125) in the control group and 35.1% (35/134) in the test group. There
      was a significant difference (p < 0.05) between the control and test groups.
      These results indicate that black tea extract is effective as a prophylactic
      agent against influenza infection.

PMID- 9248264
TI  - [Study of diarrhea-inducing strains of Escherichia coli mainly isolated in Kanto
      area between June and September 1996].
AB  - A total of 21,609 faecal specimens obtained from patients with diarrhea mainly in
      Kanto area between June and September 1996 were investigated to identify the
      causative pathogens for diarrhea. One-hundred fifty-seven strains of Escherichia
      coli of 29 different O-serotypes were isolated as the causative pathogens, which
      were previously recognized to induce severe abdominal cramps and diarrhea. Of
      these, 114 strains, in which the possibility of enterohemorrhagic E. coli due to
      their O-serotypes was predicted, were examined for the producibility of Vero
      toxins. Twenty-six (76.5%) of the 34 strains of E. coli O157 produced the Vero
      toxins, and other 8 strains were the non-producers. Twenty of the 26 producers
      produced both VT1 and VT2, whereas the other 6 strains produced VT2 only.
      Furthermore, 4 strains of E. coli O26, and 1 strain each of E. coli O125 and O126
      produced Vero toxins. Thirty-two of the 114 strains, isolated from the patients
      with diarrhea and selected as the enterohemorrhagic E. coli according to the
      specific O-serotypes, were actually confirmed produce Vero toxins. Thirty-four
      strains of E. coli O157 tested were susceptible to all antibiotics such as
      ampicillin, doxycylin, levofloxacin, fosfomycin, chloramphenicol and polymyxin B,
      and no strains resistant to levofloxacin, polymyxin B and fosfomycin were found.

PMID- 9248265
TI  - [Prognostic analysis of sepsis in patients with lung cancer].
AB  - Sepsis is one of the most serious infections occurring in patients with lung
      cancer. Thus, we determined what is most predisposing factor in prognosis of
      sepsis in lung cancer patients; the type of causative bacteria, neutropenia or
      host nutritional status. A total of 27 lung cancer patients with sepsis, which
      consisted of 23 males and 4 females (mean age 70.7 +/- 6.6), were included in
      this study. The study was conducted from 1991 to 1995. All subjects were
      classified into the survival group and the dead group. Staphylococcus aureus or
      Esherichia coli most frequently isolated from the blood of the patients in the
      survival group, while either E. coli alone or multiple organisms were predominant
      in the dead group. Neutropenia did not affect the outcome of sepsis in lung
      cancer patients. In contrast nutritional status, as determined by serum albumin
      levels, was closely related to the mortality in septic lung cancer patients.
      These results predict that the prognosis of sepsis is dependent on nutritional
      status of lung cancer patients.

PMID- 9248266
TI  - [Significance of Aspergillus fumigatus rDNA detected by polymerase chain reaction
      in diagnosis of pulmonary aspergillosis].
AB  - We have studied the clinical significance of Aspergillus fumigatus rDNA detected
      by polymerase chain reaction (PCR) for diagnosing aspergillosis. For this
      purpose, a specific and sensitive PCR assay was developed to amplify the 26S
      rDNA/intergenic spacer region of A. fumigatus. Control experiments showed that
      the set of primers used was capable of amplifying A. fumigatus DNA specifically
      and that the DNA amount of detection limit was 1 pg. Eighteen samples from 13
      patients with aspergillosis and 36 samples from 24 patients without aspergillosis
      were tested by means of PCR, culture, latex agglutination test for galactomannan
      antigen and double gel diffusion assay for precipitation of antibodies to A.
      fumigatus. PCR showed positive test in 8 among 13 patients with pulmonary
      aspergillosis. On the other hand, culture of samples detected A. fumigatus in 6
      patients. Galactomannan antigen and antibodies specific to A. fumigatus were
      positive in 2 and 6 patients respectively. These results indicated that PCR is
      the most sensitive among these 4 methods. Five patients showed negative PCR test
      despite of having pulmonary aspergillosis. Two of these patients were proved to
      have aspergillosis caused by A. flavus and A. niger. On the other hand,
      galactomannan antigen and A. fumigatus antibody were positive in one and 2
      patients, respectively. PCR was positive in 2 out of 24 patients diagnosed as not
      having aspergillosis: one patient had diagnosis of acute bronchitis, but she
      showed positive culture of A. fumigatus. The other patient had diagnosis of lobar
      pneumonia, because any pathogens were not detected before PCR assay. The PCR
      assay we developed is a useful method for diagnosing aspergillosis caused by A.
      fumigatus as compared with other conventional methods.

PMID- 9248267
TI  - [Analysis of children with tuberculosis in the past 20 years].
AB  - To characterize the clinical features of childhood tuberculosis, we analyzed the
      symptoms, signs, and laboratory findings of the 89 children with tuberculosis
      admitted to the Yokohama City University Hospital from 1975 to 1994. Compared
      with the numbers of patients admitted from 1975 to 1979, those of patients of the
      past 5 years (from 1990 to 1994) were reduced by half. Of the 89 subjects, 56.2%
      were below 3 years of age and 24.7% were under 1 year of age. 51.7% had primary
      complex and 20.2% had serious tuberculosis (tuberculous meningitis 14.6%, miliary
      tuberculosis 3.4%, and bone and joint tuberculosis 2.2%). Tuberculous children
      below 3 years of age consisted of primary complex (60.0%) and serious
      tuberculosis (32.0%). The majority (86.0%) of tuberculous children below 3 years
      of age had not received BCG vaccination. In 55 (61.8%) of 89 subjects, the
      sources of tuberculosis were clarified. Of these subjects, 83.6% were infected in
      the family. The rate of BCG inocluation tended to decrease with decreasing age,
      especially that of children below 3 years of age was 14.0%. Of the 89 subjects,
      only 16.9% proved to be smear-positive. Taken together, in order to eliminate
      tuberculous children below 3 years of age, the following is necessary; (1) BCG
      inoculation in early infancy, (2) early diagnosis of index cases with adult
      tuberculosis, and (3) prompt and appropriate family contact examination.

PMID- 9248268
TI  - [Rapid detection of influenza virus A (AH1, AH3) and B by nested-polymerase chain
      reaction].
AB  - We applied the Nested-polymerase chain reaction (PCR) for laboratory diagnosis of
      influenza virus infection. We used three primer sets for detection of influenza
      virus A (AH1, AH3) and B. The primer sets for each type (AH1, AH3, B) was able to
      detect specifically each type of influenza. We measured the sensitivity for
      detection of vaccine strains. The PCR method was able to detect 0.9 PFU/assey of
      AH1 type, 1.0 PFU/assey of AH3 type and 1.8 PFU/assey of B type. Out of 46
      isolation negative but antibody positive cases, 38 cases were positive for PCR
      (82.6%). This method is sensitive and useful for rapid diagnosis of influenza
      virus infection.

PMID- 9248269
TI  - [Clinical significance of peak body temperature, white blood cell count, and C
      reactive protein level in febrile episodes among geriatric inpatients].
AB  - To investigate the clinical implication of peak body temperature, peripheral
      blood white blood cell (WBC) count, and serum C-reactive protein (CRP) level in
      febrile symptoms among geriatric hospitalized patients, they were analyzed in 968
      febrile episodes obtained from 433 hospitalized patients in the referred
      hospital. Episodes of one day duration were most frequent (41.6%). WBC count was
      elevated over 8000/microliters in 475 episodes (49.1%) and CRP exceeded 1.0 mg/dl
      in 770 episodes (79.5%). Frequency of WBC elevation decreased and frequency of
      CRP elevation increased according to the time course. The mean value of CRP
      increased significantly according to the time course. The frequency of WBC count
      increase and CRP elevation and their averages correlated to the peak body
      temperature. The peak body temperature displayed the most striking correlation to
      the length of febrile episodes among three clinical indicators, peak body
      temperature, WBC count, and CRP level. These results indicate that the elevation
      of WBC count and/or CRP level is frequent in geriatric patients with febrile
      symptoms. Peak body temperature may serve as a clinical indicator of the severy
      of the febrile disease occurring in geriatric patients.

PMID- 9248270
TI  - [The binding activity of diglucosyl diacylglyceride derived from membranes of
      Acholeplasma laidlawii PG8 to lymphoid cells].
AB  - A chemical component has been purified from Acholeplasma laidlawii which binds to
      tissue culture cells, MOLT-4, Hut-78, but not MT-4 and Jurkat. The glycolipid in
      the membranes of A. laidlawii was extracted by Bligh-Dyer method. Further
      purification of chloroform phase of Bligh-Dyer method was performed by silicagel
      column chromatography and thin layer chromatography. Finally, the active
      component was assigned to be diglucosyl diacylglyceride by using nuclear magnetic
      resonance (1H, 13C). Furthermore, diglucosyl diacylglyceride(s) with C14 and C18
      were synthesized, by the method of Boom. Both native and synthesized
      diacylglycerides bind to MOLT-4 and Hut-78 cells. The binding activity of these
      substances to cells was inhibited by preincubation of diglucosyl diacylglycerides
      on the cover glass with clathrin. These results suggest that the binding site of
      diglucosyl diacylglycerides on cells was clathrin. It is necessary to clarify the
      biological activities of diglucosyl diacylglycerides in viral infections and
      transmission of lipoprotein and the how mechanism of envelopment of the virus
      into the cell.

PMID- 9248272
TI  - [Study on coccoid formation of Helicobacter pylori].

PMID- 9248271
TI  - [A case of the tuberculous abscess in the abdominal wall].
AB  - A case of the tuberculous abscess in the abdominal wall is reported. A 84-year
      old female was admitted to our hospital with evaluation of soft tumor at the left
      lower abdomen. She has a mass in the abdominal wall measuring 4 cm in diameter,
      and abscess in the abdominal wall was detected by ultrasonogram and CT. The
      confirmed diagnosis of abdominal wall tuberculosis was made by means of bacterial
      culture and polymerase chain reaction (PCR method) of the aspirated fluid from a
      mass. Multiple calcified lesions on the abdominal X-ray were seen, which were
      thought to past history of tuberculous peritonitis. Antituberculosis therapy of
      three-drug regimens was not effective. Four month later, resection of the abscess
      was then performed. Adhesion was demonstrated between greater omentum and
      peritoneum, therefore the abscess in the abdominal wall was considered to arise
      and advance directly from the abdominal cavity.

PMID- 9248273
TI  - [Actual status of the management of tuberculosis patients in a university
      hospital without isolation wards for infectious diseases].
AB  - We retrospectively evaluated clinical findings and the actual status of
      management of 69 tuberculosis patients admitted to the Fujita Health University
      Hospital, a hospital without isolation wards for infectious diseases, between
      1991 and 1994. The largest age group was 60s (27.5%) followed by 70s (24.6%), 80s
      (15.9%) and 50s (13.0%). Eight patients (11.6%) were in the 20s. Forty-nine
      patients were smear-positive and 22 patients were smear-negative and culture
      positive. Fourteen patients (20.3%) had a past history of pulmonary tuberculosis.
      Twelve patients (17.4%) also had diabetes mellitus, ten patients (14.5%) had
      cancer, ten patients (14.5%) gastric ulcer and five patients (7.2%) renal
      failure. Positive skin reaction to PPD was not found in eleven patients (15.9%)
      and seven of these patients were quite elderly (over 70 years old). Twenty-five
      cases (36.2%) were classified as type II (cavitary) and 29 cases (42.0%) as type
      III (non-cavitary) according to the GAKKAI classification of findings on chest X
      ray films for pulmonary tuberculosis. Twenty-four patients (34.8%) were not
      diagnosed as tuberculosis on admission by physicians in charge. Physicians in
      charge tended not to suspect smear-negative patients of tuberculosis. Most of the
      patients with cavities on their chest X-ray films were strongly suspected of
      tuberculosis on admission, but in some of them, tuberculosis was not considered
      at all. Smear-positive patients with strongly suspected tuberculosis were
      diagnosed with the disease within three hospital days, while it took about three
      weeks in patients who were not considered as tuberculosis on admission to be
      diagnosed as tuberculosis. In the case of smear-negative patients, it took about
      one month and two months respectively to diagnose the case as tuberculosis. About
      half (51.1%) of the smear-positive patients were admitted and treated in single
      bed rooms while 44.7% were attended in multiple-bed rooms for 11 days before they
      were transfered to single-bed rooms. When acid-fast bacilli were detected, 57.4%
      of the smear-positive patients were transfered to hospitals with isolation wards
      for infectious diseases, while the remaining smear-positive patients were treated
      in single-bed rooms at the university hospital. About one-third (31.7%) of the
      smear-negative patients had already left the hospital when specimens were found
      to be culture positive for tubercle bacilli. In conclusion, it is utmost
      important for physicians to suspect tuberculosis for the early diagnosis of the
      disease.

PMID- 9248274
TI  - [Cytokine producing ability of peripheral blood mononuclear cells in the clinical
      course of pulmonary tuberculosis].
AB  - Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10)-producing ability of
      peripheral blood plastic-dish adherent cells and non-adherent cells obtained from
      patients with active pulmonary tuberculosis (N = 17) and healthy controls (N =
      14) upon stimulation with purified protein derivatives (PPD) were assessed.
      Adherent cells and non-adherent cells were obtained two times from each patient
      with active pulmonary tuberculosis without any underlying diseases, on admission
      before the initiation of administering anti-tuberculous drugs and 2 months later
      from the negative conversion of Mycobacterium tuberculosis in sputum culture.
      ELISA was performed to measure IFN-gamma and IL-10 levels in culture media of
      adherent cells and non-adherent cells stimulated with PPD. IFN-gamma levels
      produced by non-adherent cells on admission were significantly higher than that
      of healthy controls (p < 0.001). Elevated IFN-gamma levels on admission was
      reduced after treatment for tuberculosis (p < 0.03), but still remained higher
      than that in healthy controls. IL-10 levels of non-adherent cells of patients
      were lower than those of healthy controls, although the difference was not
      significant. IL-10 levels produced by non-adherent cells on admission correlated
      with the time needed for negative conversion of bacilli in sputum culture (p <
      0.05). IL-10 level produced by adherent cells from nutritionally normal patients
      were significantly higher than that of healthy controls (p < 0.05), and elevated
      IL-10 level was significantly reduced after therapy (p < 0.05). In the
      normonourished patients, the time needed for negative conversion of the bacilli
      in sputum culture of patients kept higher level of IL-10 of non-adherent cells (N
      = 5) was significantly longer than that of patients reduced IL-10 level after
      therapy. These results suggest that IL-10 produced by monocytes may diminish the
      TH1 responses of patients with pulmonary tuberculosis.

PMID- 9248275
TI  - [A case of pulmonary tuberculosis complicated with gingival lesions].
AB  - A case of secondary gingival tuberculosis is presented. The case is 51 year-old
      male who had been suffering from undetected pulmonary tuberculosis visited a
      dentist because of chronic periodontal inflammation around the gingiva of the
      right upper and left lower molar teeth lasting for one year. The lesions remained
      unchanged and painful granulomatous swelling sustained in spite of the
      conservative treatment. The case was treated with the extraction of six teeth due
      to continued toothache. By pathohistological examination of gingiva and chest X
      ray examination, the case was diagnosed as tuberculosis. Chest roentgenogram
      showed active pulmonary tuberculosis, and bacteriological examination of sputum
      showed tubercle bacilli. The administration of INH, RFP and EB was started, and
      the response to the treatment was good and the pain in the gingiva disappeared
      within three weeks. Secondary gingival tuberculosis is manifested as local
      granulomatous lesions with severe pain. The incidence of gingival tuberculosis is
      very rare, but we have to keep in mind that the oral tuberculosis secondary to
      pulmonary tuberculosis could occur.

PMID- 9248276
TI  - [Primary infection type atypical mycobacteriosis (lung infection) in the Fuji
      City Central Hospital during 1989-94].
AB  - A Clinical observation was carried out on primary infection type atypical
      mycobacteriosis (lung infection) in the Fuji City Central Hospital (Fuji-shi,
      Shizuokaken, Japan) during 1989-94. 1) Twenty-five out of 118 cases (21.8%)
      admitted to the tuberculosis ward of the hospital were atypical mycobacteriosis.
      Ten out of 25 cases with atypical mycobacteriosis were primary infection (8.5%).
      2) The results of identification of atypical mycobacteria isolated from cases
      were as follows: M. avium-intracellulare complex: 4 cases M. kansasii: 3 cases M.
      scrofulaceum: 2 cases Unknown: 1 case 3) Background factor of atypical
      mycobacteriosis was observed in 6 out of 10 cases. No background factor was seen
      in 4 cases. 4) In spite of resistance to drugs of isolated mycobacteria in vitro,
      treatment by drugs such as INH, RFP, and SM was effective in clinical course.
      That is, mycobacteria in sputum converted to negative, and chest X-ray shadow
      improvement.

PMID- 9248277
TI  - [Histopathological studies of temporal bones of patients with malignant
      melanoma].
AB  - Although malignant melanoma is known to metastasize to various sites including
      the temporal bones, there have been few studies on temporal bone histopathology
      in malignant melanoma. Here we describe the temporal bone histopathology of 5
      patients (10 temporal bones) who died of malignant melanoma with multiple
      metastasis to many internal organs and bones. We investigated the temporal bone
      based on the following three points: 1) the presence of metastatic lesions in the
      temporal bone, 2) inner ear pathology, and 3) the distribution of melanin in the
      inner ear. Normal melanin distribution was also studied in 35 temporal bones of
      patients without malignant melanoma. Metastatic malignant melanoma was observed
      in 5 temporal bones from 3 patients, in two of whom the internal auditory canal
      was involved bilaterally by melanoma cell infiltration. In the remaining patient
      (one ear), metastatic melanoma was found along the dura mater of the posterior
      cranial fossa to the mastoid air cells. In the former two patients, the inner and
      outer hair cells as well as the stria vascularis showed degenerative changes to
      various extents. In particular, the inner ear changes were severe in the ear with
      the decongestion of the inner ear vessels. Melanin was found in the modiolus,
      stria vascularis, osseous spiral lamina, membranous labyrinth, and endolymphatic
      sac, as previously reported. The amount of melanin in the inner ear increased
      with age in the control patients, but was greater than in the controls, in all of
      the cases of malignant melanoma except one, in which metastatic lesions were
      present in the internal auditory canal with marked congestion of the inner ear
      vessels.

PMID- 9248278
TI  - [Relationship of Onodi cell to optic neuritis--radiological anatomy on coronal CT
      scanning].
AB  - The relationship of paranasal sinusitis to optic neuritis remains controversial.
      One of the major sources of this controversy is that there are some reports of
      rhinogenic optic neuritis (RON) in patients with mild paranasal sinusitis or with
      almost normal paranasal sinuses. The Onodi cell is a posterior ethmoid cell which
      pneumatized far laterally and to some degree superiorly to the sphenoid sinus and
      is intimately associated with the optic nerve. Coronal CT scanning is requisite
      to detect the Onodi cell; when it is present, an image of the sphenoid sinus just
      as if it were divided into top and bottom is characteristic. In our material from
      200 patients (direct coronal CT scans 10 mm in width), the Onodi cell was
      observed in 7%. A case of RON whose pathogenesis was considered to be a direct
      spread of inflammation from the localized infection of the Onodi cell is
      reported. Ethmoiditis localized to the Onodi cell seems to play an important role
      in the pathogenesis of RON. Continued careful documentation of the localized
      posterior paranasal sinus lesion around the optic canal by detailed diagnostic
      imaging and endoscopic sinus surgery is necessary to resolve the disease entity
      of RON.

PMID- 9248279
TI  - [Cell surface antigens on inflammatory cells in the paranasal mucosa of patients
      after macrolide therapy].
AB  - Low-dose and long-term administration of 14-lactone-ring macrolides (macrolide
      therapy) has been reported to be very effective in the treatment of chronic
      sinusitis, including the sinobronchial syndrome. However, the mechanism whereby
      the chronic inflammation is down-regulated is unknown. The present study was
      carried out to immunohistochemically identify the antigens expressed on the
      surfaces of inflammatory cells in the paranasal mucosa and nasal polyps of
      patients who responded well to macrolide therapy and in control patients. HLA-DR
      (a class-II antigen) was detected on relatively large, irregularly shaped cells
      and on small, round cells in the submucosa. The former cells were considered to
      be macrophages because they were CD68-positive. Thus, in the paranasal mucosa
      macrophages act antigen-presenting cells. The numbers of HLA-DR-positive cell and
      CD68-positive cells varied among the patients and did not differ significantly
      between the patients who had under gone macrolide therapy and those who had not.
      There were significantly fewer CD4-positive T lymphocytes in the submucosa of
      patients who had under gone macrolide therapy than in the control patients, but
      the number of CD8-positive T lymphocytes did not differ significantly between the
      two groups of patients. The mean ratio of the number of CD4-positive to the
      number of CD8-positive T lymphocytes (CD4/CD8) in the submucosa of the patients
      who had under gone macrolide therapy, 0.77, was significantly lower than in the
      control patients, 1.92 (< 0.01). HLA-DR expression induces differentiation of and
      cytokine production by CD4-positive T lymphocytes in the presence of co
      stimulators. The present results suggest that macrolides may affect the manner of
      interaction between antigen-presenting cells such as macrophages and CD4-positive
      T lymphocytes.

PMID- 9248280
TI  - [Influence of sleep apnea on nocturnal blood pressure].
AB  - In the present study, we subjected 65 patients to overnight monitoring and
      continuous nocturnal blood pressure measurement in order to assess the influence
      of sleep apnea on the circulatory system. Thirty-one patients were compared
      before and after surgery. The severity of sleep apnea was classified by Apnea
      Hypopnea Index (AHI), the duration of exposure to low-level oxygen (calculated as
      the desaturation time: DT), and increment of blood pressure. Before surgery, a
      significant correlation was noted between the DT and blood pressure changes.
      Therefore, this index was considered useful for assessing the influence of sleep
      apnea on nocturnal blood pressure. After surgery, improvement of AHI was greater
      than 50% in 19/31 patients (61.3%), and this result was almost the same as
      described in the literature. The improvements in DT and BP change were greater
      than 50% in 21/31 (67.7%) and 14/31 (45.2%), respectively. With regard to
      severity before surgery, AHI was > or = 50 and DT was > or = 40% in 10 and 18
      patients, respectively. Nineteen patients had BP changes > or = 40 mmHg. After
      surgery, 1,5, and 2, patients, respectively, still showed these values. Thus, a
      beneficial effect of surgery was demonstrated.

PMID- 9248281
TI  - [Functional changes in the cochlea of guinea pigs in chronic renal failure-
      electrocochleography. Effect of noise exposure].
AB  - An animal model of chronic renal failure (CRF) was created by the 5/6 nephrectomy
      procedure in guinea pigs. Levels of serum Cr and BUN were abnormally elevated at
      1,2 and 3 months after the procedure. ECoG (CAP, CM) was recorded through a
      silver ball electrode placed on the round window 1,2 and 3 months after surgery.
      EP was measured with a glass microelectrode from the scala media via the round
      window membrane. Only slight ECoG changes were seen 1 month after surgery. On the
      other hand, moderate or profound changes were observed 2 and 3 months after
      surgery. No significant decrease in EP was found in the post-surgery animals
      which distinctly showed abnormal CAP, CM, although a limited number of animals
      were studied. The above results indicate that CRF is one of the etiological
      factors of cochlear dysfunction and the sensory hair cells appeared to be the
      site of the lesion. To study the interaction between noise exposure and CRF, 1
      month post-surgery animals with only a little change in ECoG were exposed to a
      broad band noise. Changes in the ECoGs were followed up for 6 hours after the
      noise exposure. In contrast to the controls, animals with CRF did not recover
      from the reduced ECoG which occurred immediately after the noise exposure. This
      suggests synergistic interaction between noise and CRF.

PMID- 9248282
TI  - [Experimental study on injury of the rat nasal mucosa by distilled water
      irrigation, and its regeneration].
AB  - Injuries caused by distilled water and the regeneration process in the nasal
      mucosa in the respiratory region of the rat were examined electron
      microscopically and immunohistochemically by light microscopy. The mucosal injury
      was observed as exfoliation and desquamation of ciliated cells and goblet cells
      almost everywhere. The basal cells and basal membrane were intact. The
      regeneration process was completed by the migration, proliferation and
      differentiation of basal cells. The numbers of nuclear mitotic figures started to
      increase in a group of rats observed 6 hours after treatment (6-hour group),
      peaked at 48 hours, and returned to the baseline state after day 4. The BrdU
      labeling index, on the other hand, started to increase after 6 hours, peaked at
      36 hours, and returned to the baseline state after day 4. The goblet cells were
      predominant even in the 21-day group, compared to the control group. Nuclear
      mitotic figures and secretory granules were observed together in one cell in the
      36-hour group.

PMID- 9248283
TI  - [Correlation between the age-dependent changes in caloric response and in pure
      tone hearing].
AB  - Previous reports have examined the age-dependent changes of the auditory system
      or the caloric response, but results have been inconsistent. No study to date has
      correlated the age-dependent changes in caloric response with those in pure tone
      hearing in the same subjects. In this study a caloric test and a pure tone
      audiometry test were performed in 86 subjects (172 ears), age range 24 to 84
      years of age, including 12 otoneurologically healthy volunteers (24 ears), and 74
      tinnitus patients without subjective hearing loss (148 ears). The maximal slow
      phase eye velocity (SPEV) of caloric nystagmus response and the mean hearing
      level at high frequencies were measured and the age-dependent changes in these
      scores were compared. The following results were obtained. 1) The SPEV of caloric
      nystagmus, which remained unchanged until markedly advanced age, decreased
      significantly from 65 years of age in men and from 75 years in women; the change
      occurring earlier in men than in women. 2) The hearing level at high frequencies
      decreased abruptly from 50 years of age with a more gradual change from 75 years
      was significantly lower in men than in women over 65 years of age. 3) There was a
      weak but significant correlation between the age-dependent changes in SPEV and
      those in hearing level at high frequencies.

PMID- 9248284
TI  - ["Unkei" in Heisei period].

PMID- 9248285
TI  - [Prevalence of serum anti-Helicobacter pylori IgG antibody in persons with severe
      motor and intellectual disabilities--comparison between institutionalized persons
      and persons living at home].
AB  - The seroprevalence of an anti-Helicobacter pylori antibody (ELISA) was
      investigated in institutionalized persons with severe motor and intellectual
      disabilities (SMID). The rate of seropositivity was significantly higher in
      persons with SMID under 29 years of age than in age-matched controls and in
      institutionalized patients with muscular dystrophy. No difference in
      seropositivity among SMID patients was found between those in our and other
      institutions. Therefore, it is speculated that Helicobacter pylori infection
      occurs soon after the institutionalization of SMID patients. Persons with SMID
      living at home, in their teens and twenties, had lower seropositivity than that
      of institutionalized patients but higher than controls. These data implicate the
      life style of persons with SMID and long-term institutionalization as one of
      important risk factors of Helicobacter pylori infection.

PMID- 9248286
TI  - [Efficacy of rectal diazepam suppository in the prophylaxis of febrile seizures:
      comparison with rectal chloral hydrate suppository].
AB  - We evaluated the efficacy of diazepam and chloral hydrate given rectally for the
      prophylaxis of recurrence of febrile seizure. The dose were 0.4 mg/kg for
      diazepam and 250 mg (for children younger than 3 years old) or 500 mg (for over 3
      years old) for chloral hydrate. Another dose was given after an interval of 8
      hours if body temperature continued to exceed 38.0 degrees C. Among the 452
      patients with febrile seizures who visited our hospital from Jan. 1993 to Jun.
      1995, 113 were studied who had at least one febrile episode in the follow-up
      period that extended over 6 months. These patients were divided into two groups:
      Group D (72 patients given diazepam) and Group C (41 patients given chloral
      hydrate). In group D and C, the numbers of febrile episodes were 238 and 167, and
      those of recurrent seizures 8 (3.8%) and 29 (20.4%), respectively. The
      recurrences rate was significantly higher in the latter group (p < 0.005). There
      was no statistical difference as to the mean dosage of diazepam or chloral
      hydrate between the patients with and without recurrence. The numbers of patients
      with seizure recurrence were 8 (11.1%) in group D and 12 (29.3%) in group C,
      being significantly larger in the latter (p < 0.005). Diazepam produced more
      adverse effects than chloral hydrate did. Thus diazepam suppositories for the
      prevention of recurrence of febrile seizures were more effective than chloral
      hydrate suppositories.

PMID- 9248287
TI  - [The relationship between MR images and clinical findings in neuronal migration
      disorders].
AB  - Among the variable manifesting conditions of neuronal migration disorders, mental
      retardation, motor disturbance and epilepsy are the main features of
      developmental disabilities. We analyzed the relationship between clinical
      symptoms and magnetic resonance (MR) images, including surface anatomy scan
      (SAS). Thirty nine patients (23 males, 16 females; mean age 6.1 years) with
      neuronal migration disorders were studied. The diagnoses were cerebral palsy in
      23 cases, mental retardation in 4. West syndrome in 4, Fukuyama type congenital
      muscular dystrophy (FCMD) in 6. Walker-Warburg syndrome in 1 and Dubowitz
      syndrome in 1. Cortical dysplasias were classified into the following 7 groups,
      mainly based on the SAS findings: complete agyria (AG 1), mixture of agyria and
      pachygyria (AG 2), bilateral complete pachygyria (BP 1), diffuse pachygyria with
      marked widening of the bilateral superior frontal gyrus (BP 2), unilateral
      pachygyria with hemispheric atrophy or hemimegalencephaly UP), focal cortical
      dysplasia (FP) and other findings such as solitary schizencephaly (Others). Most
      cases of AG 1 and AG 2 showed spastic quadriplegia (6/7) and symptomatic
      generalized epilepsy (5/7), whereas cases of BP1 showed spasticity only in 1/8
      and epilepsy in 7/8. Hemiplegia was observed in 6/7 of UP, 2/8 of FP and 2/4 of
      Others. Partial epilepsy was observed in 2/7 of UP and 1/8 of FP. Intellectual
      level was variable in BP 1, UP, FP and Others, but all cases showed severe mental
      retardation in AG 1, AG 2 and BP 2. BP 2 was observed in all cases of typical
      FCMD (5/5). The birth weight was less than 2,500 g in 6/7 of UP. The structural
      findings well correlated with clinical symptoms and epileptic seizure types. The
      surface anatomy scan was a very useful technique for detecting cortical
      dysplasias.

PMID- 9248288
TI  - [Factors associated with the prognosis of bacterial meningitis in children].
AB  - Treatment of bacterial meningitis depends on its severity. The signs, symptoms,
      and laboratory values of 51 patients with bacterial meningitis admitting to the
      Department of Pediatrics at Sendai City Hospital from January 1985 to December
      1994 were analyzed in order to evaluate their prognostic value. The overall
      mortality rate was 3.9%. The incidence of neurological deficit on discharge was
      31.4%. According to their prognoses, patients were divided into two groups: those
      who recovered with no detectable disabilities (good prognosis) and those who died
      or were left with neurological deficits (poor prognosis). An analysis of these
      groups using Fisher's exact probability test revealed that the following risk
      factors were associated with poor prognosis: 1) duration of fever (including the
      periods of relapse) for more than 10 days ; 2) abnormal findings on brain
      imaging, such as cerebral infarction, cerebral hemorrhage, cerebral abscess and
      subdural effusion: 3 initial serum CRP value above 16 mg/dl; 4) initial CSF
      glucose value below 12 mg/dl; and 5) initial CSF LDH value above 220 IU/l.
      Streptococcus pneumoniae infection carried the worst prognosis: the causal
      organism of both the two fetal cases was S. pneumoniae. The incidence of poor
      prognosis was also high in S. pneumoniae meningitis (60.0%), compared to those by
      Hemophilus influenzae (46.7%) and group B streptococcus (25.0%). In the cases in
      which causal agents were not detected, this incidence was as low as 10 percent,
      showing significant difference from cases in which causal agents were identified.
      In order to improve the prognosis of bacterial meningitis, factors associated
      with poor prognosis should be recognized at early stages of the illness.

PMID- 9248289
TI  - [A family of dentatorubral-pallidoluysian atrophy: clinical and neuroradiologic
      studies].
AB  - We described a family of dentatorubral-pallidoluysian atrophy (DRPLA). The mother
      presented with cerebellar ataxia at 35 years of age and thereafter her
      neurological symptoms became exacerbated. Her daughter had mental retardation
      during the preschool period and epilepsy at 10 years. Her son presented with
      epilepsy at 14 years. Their clinical phenotypes demonstrated maternal
      anticipation in this family. Genetical analysis of their DNA revealed CAG repeat
      expansion of the DRPLA gene, the number of which was 51 (mother), 65 (her
      daughter), and 53 (her son). MR imaging showed disappearance of T, shortening of
      the red nucleus in the mother and her daughter in contrast to the normal
      appearance in her son. MR imaging was effective in evaluating neuropathological
      changes in the DRPLA patients.

PMID- 9248290
TI  - [A case of juvenile Huntington's disease presenting dystonia and confirmed by DNA
      analysis].
AB  - We reported a 13-year-old boy with juvenile Huntington disease diagnosed by DNA
      analysis. Symptoms started with dysarthria at 6 years of age, which was followed
      by progressive dysgraphia and gait disturbance due to dystonia from 7 years, and
      by epileptic seizures from 12 years. Magnetic resonance imaging revealed atrophy
      of the bilateral caudate nuclei and T2- and proton-weighted high intensity area
      in both putamina. The CAG (cytosine-adenine-guanine) trinucleotide repeat on
      chromosome 4 p16 was markedly expanded to 81. For a child with dystonia with
      mental deterioration, juvenile Huntington disease should be considered in the
      differential diagnosis.

PMID- 9248291
TI  - [Cousins with X-linked recessive myotubular myopathy].
AB  - We describe two cousins with severe infantile form of myotubular myopathy. In
      Japan this disease has previously been reported in only three families. Case 1.
      The propositus, a 2-year-5-month-old boy, had been on a respirator since birth.
      He had a history of severe neonatal asphyxia and sequential hypotonia with
      dyspnea. Findings diagnostic of congenital myotubular myopathy, such as central
      nuclei and peripheral halo of muscle fibers, were demonstrated in his biopsied
      muscle. Case 2. A male the cousin of case 1 had congenital myopathy and died at 3
      months of age due to respiratory failure. His muscle biopsy disclosed the
      identical findings as had been seen in case 1. These two cases were born to twin
      mothers, suggesting X-linked recessive inheritance. Early diagnosis and proper
      treatment of myotubular myopathy are important, because this condition may be
      erroneously-interpreted as the sequelae of neonatal asphyxia.

PMID- 9248292
TI  - [A semantic-pragmatic learning disabled child who showed a discrepancy between
      the abilities of verbal and non-verbal comprehension].
AB  - A learning disabled (LD) child with disorder of verbal semantic comprehension was
      reported. This case showed normal ability of non-verbal semantic comprehension.
      He was not able to understand the meaning of what he read aloud and/or repeated,
      which he did well. The focus of his brain dysfunction in the left temporal lobe
      was revealed by SPECT in spite of MRI findings of no particular lesions.
      Neuropsychological and cognitive-psychological findings were similar to those
      reported of adult sensory aphasias with localized lesions.

PMID- 9248293
TI  - [A child showing memory disorders].
AB  - We report a girl with memory disorders. Her memory remained disturbed regardless
      of input or output modalities. She could recognize items and recall them
      randomly, but she could not recall them in the correct order. She showed memory
      impairment with regard to temporal context. We could clearly demonstrate this by
      cognitive psychological and neuropsychological tests and by analyzing the results
      of ordinary intelligence tests by input and output modalities. These results
      suggest that subjects who show memory disorders should undergo further resting to
      clarify the qualitative aspects of these disorders and the possibility that
      learning disabilities caused by memory disorders should be considered a specific
      type of learning disability.

PMID- 9248294
TI  - [Partial seizures following aseptic meningoencephalitis: an unusual case].
AB  - We reported a case of partial seizures following aseptic meningoencephalitis. A 2
      year-10-month-old boy was admitted to our hospital because of generalized
      seizures with fever. He had no history of previous seizures and had been well
      until 8 days before admission. He had been given a 4th DPT (diphtheria, tetanus
      toxoid and pertussis) vaccine 9 days before admission, and had developed fever
      and exanthema on the trunk the following day. Both fever and exanthema recurred
      repeatedly thereafter. After admission, he suffered from generalized seizures
      without fever and many kinds of partial seizures with psychiatric symptom.
      Despite administration of several antiepileptic drugs, these seizures persisted
      for one and half months, occurring 5 to 18 times a day. Thirty-six days after
      admission, MRI showed multiple dark areas on T1-weighted images and bright areas
      on T2-weighted images in the bilateral frontal area. We considered these to be
      due to cerebral vasculitis associated with aseptic meningitis. The patient's
      seizures were finally controlled by zonisamide administration. At the same time,
      fever went down. He has since shown normal development without seizures for 18
      months.

PMID- 9248295
TI  - The organization of participation in general practice.

PMID- 9248296
TI  - Community participation in primary care. An historical and international
      perspective.

PMID- 9248297
TI  - Developing an inner city health resource centre.

PMID- 9248298
TI  - The Heeley Health Project.

PMID- 9248299
TI  - A fundholder's support for community participation.

PMID- 9248300
TI  - A celebration of health through art.

PMID- 9248301
TI  - The Wells Park Health Project.

PMID- 9248302
TI  - Yaxley Group Practice and Patients' Association.

PMID- 9248303
TI  - Community involvement in a changing world.

PMID- 9248304
TI  - Reorientating health promotion in primary care to participative approaches.

PMID- 9248306
TI  - What do we get out of being involved with the local community?

PMID- 9248305
TI  - Ideas for the evaluation of community participation initiatives.

PMID- 9248307
TI  - What is good general practice? A philosophical study of the concept of high
      quality medical care.

PMID- 9248308
TI  - Shared care for diabetes. A systematic review.

PMID- 9248309
TI  - Influences on computer use in general practice. Report of a one-year study on
      behalf of the Royal College of General Practitioners.

PMID- 9248310
TI  - Significant event auditing. A study of the feasibility and potential of case
      based auditing in primary medical care.

PMID- 9248311
TI  - Does the health status of chronically ill patients predict their judgements of
      the quality of general practice care?
AB  - Patients' health status as well as patients' judgements of care are used for
      assessing patients' perspectives, but the relation between those two concepts is
      unclear. In this study we explored whether health status predicts patients'
      judgements of the quality of general practice care. Hand-distributed and mailed
      surveys were performed by 28 general practitioners in The Netherlands.
      Chronically ill patients were approached when visiting the general practice or
      drawn from the practice registers. Health status was measured by WONCA/COOP
      charts, and patients' judgements by the CEP, a previously validated
      questionnaire. The response rate was 63% (n = 762). When controlled for other
      patient characteristics, a poor overall health predicted less positive judgements
      of medical care, information, counselling, relation and communication, continuity
      of care and the organization of appointments (p < 0.01). Poor mental well-being
      predicted less positive judgements of the cooperation between care providers and
      a stronger need for more care (p < 0.001). The four other aspects of health
      status did not predict the patients' judgements. Judgements about the premises
      and the availability for emergencies were not predicted by health status. It can
      be concluded that a multidimensional approach should be used for interpreting the
      relations between patients' health status and their judgements of general
      practice care.

PMID- 9248312
TI  - Development of a direct weighting procedure for quality of life domains.
AB  - The Schedule for the Evaluation of Individual Quality of Life allows individuals
      to nominate the domains they consider most important to their quality of life and
      to use their own value system when describing the functional status and relative
      importance of those domains. The weights for domain importance are derived
      through a procedure called judgement analysis. As judgement analysis is
      impractical for individuals with cognitive impairment and in many clinical
      situations, a shorter, direct weighting procedure has been developed. To test the
      new procedure, 40 healthy individuals completed both direct and judgement
      analysis weightings, at t1 and 7-10 days later (t2). After a further 7-10 days
      (t3), they were asked to identify the weight profiles they had previously
      produced using each method. The weights produced by the two methods differed on
      average by 7.8 points at t1 and 7.2 points at t2. The direct weights changed on
      average by 4.5 points from t1 to t2, while the judgement analysis weights changed
      by 8.4 points. At t2, 55% of individuals were able to identify the direct weights
      they had previously produced. The new procedure demonstrates stability and
      validity but is not interchangeable with judgement analysis. The most appropriate
      ways of using and interpreting both procedures are discussed.

PMID- 9248313
TI  - Assessing health-related quality-of-life and health state preference in persons
      with obesity: a validation study.
AB  - The objective of this study was to assess the reliability, validity and
      responsiveness of a new health-related quality-of-life (HRQOL) measure containing
      global and obesity-specific domains and an obesity-specific health state
      preference (HSP) assessment. A total of 417 obese and 'normal' weight individuals
      completed these assessments. Internal consistency and test-retest reliability
      were demonstrated, with Cronbach's alpha, intraclass correlation coefficient and
      kappa values well above the acceptable level for most scales. Construct validity
      hypotheses were confirmed by examining scale correlations. The normal weight
      individuals reported statistically significantly better functioning and well
      being on the majority of the HRQOL scales and HSP than obese individuals.
      Guyatt's statistic of responsiveness was moderate to high for all the scales and
      items in the weight-loss and weight-gain groups; however, many of the scales and
      items in the weight-stable group also displayed responsiveness. The results of
      this study support the reliability and validity of these assessments. However,
      further testing is needed to evaluate the responsiveness of both assessments in a
      weight-stable group.

PMID- 9248314
TI  - Measuring health status with the Dartmouth COOP charts in low-functioning
      elderly. Do the illustrations affect the outcomes?
AB  - The Dartmouth COOP method consists of seven questions measuring seven domains of
      health status: physical fitness, feelings, daily activities, social activities,
      change in health status, current overall health perceptions and bodily pain. Each
      question has five response options and each option is accompanied by an
      illustration. In this paper, we present the results of a randomized study of the
      effects of the illustrations of the seven Dartmouth COOP charts in a low
      functioning elderly sample. In addition, the subjective evaluation of the
      illustrations was examined. The results showed no significant differences between
      the outcomes obtained with the illustrated COOP charts and the unillustrated COOP
      charts: the mean scores, patterns of intercorrelations and associations with
      other measures for the research participants who filled in the illustrated COOP
      charts hardly differed from those obtained from the participants who filled in
      the unillustrated charts. Furthermore, the results showed that approximately
      three-quarters of the research participants considered the illustrations
      informative, while approximately 17% of the participants considered the pictures
      exaggerated. We conclude that, as long as there is no empirical support for the
      advantages of the COOP charts with respect to cross-cultural standardization or
      use in subjects who have, for example, difficulty in reading, there seems to be
      no need for the illustrated COOP charts. The results of our study showed that
      both types of COOP charts appear to be interchangeable.

PMID- 9248315
TI  - Patient-based health status measurement in clinical practice: a study of its
      impact on epilepsy patients' care.
AB  - The objective was to assess the potential benefits of the routine use of the MOS
      SF-36 Health Survey (SF-36) in the care of ambulatory patients. The design was a
      longitudinal, prospective, randomized, controlled study set in the outpatient
      neurology clinic at the New England Medical Center. There were 163 consecutive
      patients with epilepsy who had 210 follow-up visits with one of two
      epileptologists. The patients completed the SF-36 before the patient-physician
      encounter and the forms were optically scanned. The SF-36 results of the
      intervention group patients were given to the physicians before the encounter and
      withheld for control group patients. For intervention group patients, the
      physicians completed a questionnaire assessing the impact of the SF-36 on the
      process of care. After the visit, all patients completed a satisfaction
      questionnaire. The main outcome measures were the physicians' responses to
      standardized questions about the usefulness of the SF-36 for communication with
      and management of epilepsy patients and the patients' responses to standardized
      questions about their satisfaction with care. The physicians indicated that the
      SF-36 provided new information in 63% of the intervention group encounters. A
      change in therapy was prompted in 13%. The physicians rated the SF-36 as at least
      moderately useful for communication in 14% of the encounters and to management in
      8%. The lower (indicating worse health status) the patients' SF-36 scale scores,
      the more useful the SF-36 results were rated by the physicians for communication
      and management. It was concluded that the routine use of health status measures
      may enhance patients' care.

PMID- 9248316
TI  - Health outcomes by self-report: validity of the SF-36 among Australian hospital
      patients.
AB  - This paper examines the performance of the SF-36 as a self-reported outcome
      measure in a diverse sample of Australian hospital in-patients. The data derive
      from the Care Continuum and Health Outcomes Project with a total of 2088 randomly
      selected patients, yielding a response rate of 80%. Distributions, completion
      rates and, in particular, correlates of measures were used to investigate the
      validity of the SF-36 according to clinical and psychometric criteria. Physical
      functioning, bodily pain, role limitations-physical, general health and vitality
      scales better represented physical than mental health, with the relative strength
      decreasing in that order; while mental health, role limitations-emotional and
      social functioning scales better represented mental health, with the relative
      strength decreasing in order. A cultural dimension was a strong independent
      correlate of all scales. While the SF-36 performed satisfactorily, there were
      weaknesses: the social functioning scale was too narrow to cover social health,
      both role limitations scales had crude response categories and particular
      subgroups, the frail elderly and those with complex health conditions, required
      measures with finer gradings for scales such as physical functioning and bodily
      pain. Further testing is needed to develop self-reports for use in hospital
      outcomes measurement which is already proposed in Australia.

PMID- 9248317
TI  - Discriminative aspects of two generic and two asthma-specific instruments:
      relation with symptoms, bronchodilator use and lung function in patients with
      mild asthma.
AB  - The objective of this study was to compare the two most frequently used asthma
      specific quality of life (QOL) questionnaires and two generic QOL questionnaries
      with clinical data in order to establish their ability to discriminate in asthma
      severity, also referred to as cross-sectional construct validity. We conducted a
      multicentre, randomized, placebo-controlled study investigating the long-term
      effects of the long-acting beta 2-agonist formoterol in asthma patients using
      inhaled corticosteroids and short-acting beta 2-agonists. Before randomization,
      the peak expiratory flow (PEF) and use of beta 2-agonists for relief of symptoms
      were recorded twice daily for 1 month. At the end of the run-in period, the
      forced expiratory volume in 1 s (FEV1), airway hyper-responsiveness (PC20
      methacholine) and QOL were measured, using two asthma-specific questionnaires,
      the Asthma Quality of Life Questionnaire (AQLQ) and the Living with Asthma
      Quality of Life Questionnaire (LWAQ), as well as two generic questionnaires, the
      Short Form 36 (SF-36) and the Psychological General Well Being (PGWB) index. The
      quality of life of the patients (n = 110) was only mildly impaired. The mean
      symptom score was 3.6 on a scale of 0-21 and the mean FEV1 was 65% of that
      predicted. The correlations between the QOL parameters and objective measures of
      asthma severity, such as the FEV1, PEF and PC20, were low (0.01-0.37). The
      correlations between the QOL parameters and subjective measures of asthma
      severity, such as symptom scores (range 0.26-0.65) and beta 2-agonist use for the
      relief of symptoms (0.09-0.39), were higher. The correlations of the activity and
      symptoms domains of the AQLQ with diary-obtained symptom scores were r = 0.50 (p
      < 0.0001) and r = 0.65 (p < 0.0001), respectively. The correlation between the
      physical construct of the LWAQ and symptom scores was r = 0.42 (p < 0.001) and
      that between the physical sumscore of the SF-36 and symptom scores was r = 0.50
      (p < 0.001). The correlation between the PGWB and symptom scores was r = 0.41 (p
      < 0.001). The relation between the FEV1, PEF and PC20 and QOL was very low. The
      QOL measurements related well to the symptom scores. The AQLQ had a better cross
      sectional construct validity than the LWAQ. The cross-sectional construct
      validity of the SF-36 was surprisingly high for this group of patients and the SF
      36 performed better than the PGWB and LWAQ.

PMID- 9248318
TI  - Health-related quality of life: an indicator of quality of care?
AB  - There is an increasing interest in the use of outcome indicators to monitor the
      quality of care. Traditionally, outcome indicators have been based mainly on
      biological indicators reflecting death or disease. Now that various instruments
      for health status measurement have become available, questions have been raised
      as to the potential application of health status scores in monitoring the quality
      of care. This paper identifies conditions which should be fulfilled before such
      applications can be recommended. Firstly, the relationship between care delivery
      processes and health status outcomes must be established. In order to achieve
      this, health status measures which are clearly able to detect health status
      variations between groups of patients (i.e. discriminative ability) and
      variations over time (i.e. sensitivity to change) are needed. Secondly, health
      status data should be available, preferably from established data collection
      registries (e.g. computerized hospital records or national registries) where data
      relating to the description of variations in health status (between physicians,
      hospitals, regions, etc.) are routinely collected. Thirdly, methods should be
      found to collect additional data, including 'case-mix' information and health
      status reference data, in order to enable the interpretation of variations in
      health status. Because most of these conditions are currently not being
      fulfilled, we conclude that the state-of-the-art of health status measurement has
      not yet matured sufficiently to allow for the use of health status as an
      indicator of quality of care. The present paper provides a framework for both
      future research and data collection that is needed to improve the applicability
      of health status measures as quality-of-care indicators.

PMID- 9248319
TI  - [Cytokine expression and hematopoietic recovery after transplantation].

PMID- 9248320
TI  - [The roles of the cytokines in GVHD--the analyses and the prevention of murine
      GVHD].

PMID- 9248321
TI  - [Present status of donor leukocyte transfusion for leukemia. Relapse after
      allogeneic bone marrow transplantation in Japan].

PMID- 9248322
TI  - [Current status and problems of G-CSF-induced mobilization of peripheral blood
      stem cell].

PMID- 9248323
TI  - [G-CSF-combined preparatory regimen for autologous peripheral blood stem cell
      transplantation in acute myelogenous leukemia].

PMID- 9248324
TI  - [Recombinant human G-CSF combined regimen for allogeneic BMT in myeloid
      leukemias].

PMID- 9248325
TI  - [Prognostic factors of follicular lymphoma treated with combination
      chemotherapy].
AB  - This study investigated 72 patients (12.4%) with follicular lymphoma among 582
      patients with non-Hodgkin's lymphoma admitted to our department. Treatment
      achieved complete remission (CR) in 83.3% of the follicular lymphoma patients,
      with an overall 5-year survival rate of 63.7%. The 5-year survival rate was 76.9%
      for the 60 patients who achieved CR, and this rate was significantly higher than
      that for patients who achieved only partial remission (PR) (p < 0.01). The 5-year
      survival rate was 40% with the CHOP regimen and 74.3% with the COP-BLAM regimen.
      The 3-year survival rate for biweekly COP-BLAM was 88.4%. The 5-year disease free
      survival rate for patients who achieved CR was 80.5%. The rate reached a plateau
      after 42 months, and the same survival was maintained for more than 10 years.
      These results suggest that intensive chemotherapy is effective even against
      follicular lymphoma. The 5-year survival rate for patients who achieved PR,
      suggesting the importance of the response to initial chemotherapy.

PMID- 9248326
TI  - [Treatment results in childhood acute myeloblastic leukemia--a report of clinical
      trials of a past decade from the Japanese children's Cancer and Leukemia Study
      Group (CCLSG)].
AB  - Treatment results were evaluated in 167 children with acute myeloblastic leukemia
      (AML) treated on four protocols (ANLL 861, 8912, 9205, APL-ATRA) of the
      Children's Cancer Leukemia Study Group. In the ANLL 9205 protocol, anthracycline
      was used with a continuous infusion of cytosine arabinoside, followed by an
      intensive sequential post remission chemotherapy of short duration, 42/46
      patients (91.3%) achieved complete remission, and 58.8% of these patients
      projected a 3-year disease free survival. These results were apparently superior
      to those obtained with the ANLL 861 & 8912 protocols, which used conventional
      doses of multi drugs followed by a moderate post remission chemotherapy of long
      duration. This favorable response with the ANLL 9205 protocol was attributed
      mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as
      compared to those in the previous two protocols (91.3% in ANLL 9205 vs 57.9% in
      ANLL 861 + 8912; p < 0.05). No significant difference in the patients outcome was
      found between the chemotherapy group and allogenic bone marrow transplantation
      group in the ANLL 9205 study. The patients with the M3 FAB subtype treated with
      the APL-ATRA protocol which consisted of an alternative use of all-trans retinoic
      acid and chemotherapy significantly prolonged event free survival as compared
      with the patients treated with ANLL 861/8912 protocols without all-trans retinoic
      acid.

PMID- 9248327
TI  - [Successful high-dose chemotherapy combined with autologous bone marrow
      transplantation in a case of refractory follicular lymphoma].
AB  - A 34-year-old patient with follicular lymphoma who was treated with CHOP followed
      by COPP for 3 years, became resistant to treatment in December 1993. Histological
      findings and surface markers of cervical lymph node cells revealed no change from
      previous findings. Tumor cell involvement of bone marrow was also observed by
      molecular analysis of DNA fragments with bcl-2 oncogene and J-H gene probes.
      Following 2 courses of salvage chemotherapy with NOAC-M regimen (novantrone,
      cytarabine and methylprednisolone), There was an 88% reduction of tumor mass on
      computed tomographic findings. Through the use of polymerase chain reaction
      analysis of residual cells with the bcl-2 translocation, we confirmed the in vivo
      purging of tumor cells from bone marrow and we harvested marrow cells for
      autologous transplantation. After high-dose chemotherapy (HDC) with ranimustine,
      cisplatin, etoposide and cyclophosphamide followed by bone marrow transplantation
      (BMT), complete remission was achieved. The patient has survived for 16 months
      and remains disease free. The standard chemotherapy regimen for advanced low
      grade non-Hodgkin's lymphoma has not yet been defined. Although we must follow
      this patient carefully to determine the effect of HDC with BMT for a long time,
      this seems to be an effective complementary treatment for patients responding to
      conventional salvage regimens.

PMID- 9248328
TI  - [Mantle cell lymphoma with multiple extranodal involvement].
AB  - A 79-year-old male was admitted to our hospital because of general fatigue and
      night sweat. Physical examination showed generalized superficial lymphadenopathy,
      marked splenomegaly, and tumors in the conjunctiva and the abdomen. Chest X-ray
      and computed tomography (CT) revealed pleural effusion and intrathoracic
      lymphadenopathy. Abdominal ultrasonography and CT showed hepatosplenomegaly and
      intraperitoneal tumors. Upper gastrointestinal fiberscopy revealed multiple
      polypoid lesions and ulcers in the duodenum and the stomach. Involvement of
      relatively small-sized lymphocytes with cleaved nuclei was identified in each
      biopsied specimen from a cervical lymph node, a tumor in the conjunctiva,
      gastrointestinal polypoid lesions, and the bone marrow. Surface marker analysis
      of abnormal lymphocytes in the bone marrow revealed that CD5, CD19, and CD20 were
      strongly positive, but CD23 was weakly positive. Although (11:14)(q13:q32)
      translocation was not identified by chromosome analysis of bone marrow cells,
      Northern blot analysis of bone marrow cells revealed overexpression of the PRAD1
      oncogene. Diagnosis of mantle cell lymphoma (MCL) was made. Combination
      chemotherapy by cyclophosphamide and vincristine was not effective, but etoposide
      perorally given at a dose of 50 mg per day was effective. In MCL, extranodal
      involvement of a digestive tract and bone marrow is well known. This case
      suggests that involvement of multiple organs including lacrimal glands and pleura
      could be characteristic of MCL cells.

PMID- 9248329
TI  - [Sudden cardiac tamponade due to hemorrhagic myocarditis after preconditioning
      marrow transplantation with cyclophosphamide in a patient with aplastic anemia].
AB  - A 28-year-old male was diagnosed as aplastic anemia in 1983. He maintained on
      corticosterone with a large transfusion requirement for being resistant to other
      therapies, and combined with hemochromatosis at 20-year-old. In February 1994, he
      was admitted to the hospital for consideration of BMT. Echocardiogram was normal
      on admission. He was transplanted with bone marrow from his HLA-matched MLC
      negative sister following contained of TLI (7.5 Gy) and CY 50 mg/kg for four days
      on March 10 1994. Disturbance of consciousness appeared, an echocardiogram showed
      severe pericardial effusion on day 1 after BMT. He was diagnosed cardiac
      tamponade, pericardiocentesis was done immediately and 100 ml pericardial
      effusion was removed. Transiently he became alert, however, irreversible cardiac
      arrest occurred on day 2. Postmortem examination revealed thickened left
      ventricles with intramyocardial hemorrhage. It seems necessary to reduce CY, or
      substitute it with anti-thymocyte globulin (ATG) or TBI etc. for BMT in aplastic
      anemia accompanied by hemochromatosis.

PMID- 9248330
TI  - [Improvement of bleeding tendency and normalized platelet count increment
      following splenectomy in a patient with refractory anemia].
AB  - A 72-year-old woman with refractory anemia had severe bleeding tendency. Since
      1994, platelet transfusions (10 units three times per week) were unable to
      maintaining her platelet count over 10 x 10(3)/ microliter. Her hemoglobin was
      decreased to 3.9 g/dl as a result of bleeding from early gastric cancer. At one
      hour after posttransfusion corrected platelet count increment (1-hour CCI) was
      slightly low, as 14 x 10(3)/microliter/m2. A 24-hour posttransfusion CCI (24-hour
      CCI) and the (24-hour CCI)/(1-hour CCI) ratio were markedly low, as
      0.5/microliter/m2 and 0.36, respectively. Anti-HLA antibody was not detected. The
      ineffectiveness of platelet transfusion was suspected to be highly associated
      with splenomegaly. Her spleen had been gradually increased in size since the
      first clinical examination. She underwent both subtotal gastrectomy and
      splenectomy, while receiving 40 units of platelet transfusion. After splenectomy,
      the 1-hour CCI and the (1-hour CCI)/(24-hour CCI) ratio markedly improved (76 x
      10(3)/microliter/m2 and 0.79, respectively). Cutaneous bleeding halted and there
      have been no further episodes, despite less frequent platelet transfusions. This
      is the first report in which bleeding tendency and CCI were improved by
      splenectomy in a case of myelodysplastic syndrome.

PMID- 9248331
TI  - [Successful treatment of subdural hematoma with operation in a patient with acute
      promyelocytic leukemia].
AB  - A 51 year-old male admitted with petechiae and headache. Acute promyelocytic
      leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed.
      He received all-trans retinoic acid (ATRA) with enocitabine and daunomycin for
      induction chemotherapy, and supportive therapy for DIC. On 2nd day after
      admission, subacute subdural hematoma was confirmed with CT scan. He had
      anisocoria and disturbance of consciousness, and was treated with neurosurgical
      operation for his life saving on the 3rd day. Although DIC was continued at this
      time, the operation was done without problem. The recurrence of hematoma has not
      occurred after the operation. Furthermore, the findings of DIC disappeared by the
      day 6 following induction therapy. He achieved a complete remission including
      cytogenetic findings on 35th day after administration of ATRA and received 3
      times of combination chemotherapy as consolidation therapy. It may be difficult
      to do neurosurgical treatment in the setting of DIC. However, we should consider
      whether the indications for surgery operation according to the condition of each
      patient.

PMID- 9248332
TI  - [Splenic lymphoma with villous lymphocytes and complex chromosomal abnormality].
AB  - We report a 70-year-old Japanese man who had splenic lymphoma with villous
      lymphocytes and a complex chromosomal abnormality. No monoclonal gammopathy was
      present. The peripheral blood film showed lymphocytes with thin and short villi
      arising from one or two poles of the cells. These cells were negative for
      tartrate-resistant acid phosphatase stain. Immunophenotyping of peripheral blood
      lymphocytes showed moderate to strong expression of surface membrane IgM, IgD,
      IgA, and lambda as well as CD19, CD20, CD21, CD24, and HLA-DR. In addition, there
      was weak CD5, CD22, and CD25 expression, but no CD10, CD11c, CD23, CD38, or B-ly
      7 expression. All 20 metaphases obtained from peripheral blood cells cultured for
      5 days with lipopolysaccharide showed an abnormal karyotype: 47, XY, +der(3) t(3;
      13) (q26; q12) inv(3) (?), t(7; 14), (q21; q11), der(13) t(3; 13) (q26; q12). Our
      patient followed a relatively benign clinical course and splenectomy was not
      performed.

PMID- 9248333
TI  - [Improvement of respiratory burst by individual neutrophils from a patient with
      chronic granulomatous disease, type X91- under treatment by granulocyte colony
      stimulating factor for multiple liver abscess].
AB  - A 20-year-old male with chronic granulomatous disease (CGD) was admitted with
      multiple liver abscesses. He had already been diagnosed as CGD, type X91-, when
      he was 10 years old. He was successfully treated with antibiotics and granulocyte
      colony-stimulating factor (G-CSF) combined with continuous drainage of abscess.
      Employing flow cytometry, respiratory burst by individual neutrophils was
      measured using 2', 7'-dichlorofluorescein. The fluorescence intensity in all
      individual neutrophils from the patient under G-CSF treatment was higher than the
      one without G-CSF. G-CSF can be one of effective therapies for infection in some
      patients with CGD such as X91-.

PMID- 9248334
TI  - ["Forced mouth opening reaction" associated with corticobasal degeneration].
AB  - Corticobasal degeneration (CBD) is a slowly progressive disorder characterized by
      an asymmetrical akinetic-rigid syndrome, supranuclear ophthalmoplegia, dystonia,
      often accompanied by involuntary movements, particularly myoclonus, and
      associated with lateralized cortical signs such as alien limb behavior and
      apraxia. Computerized tomography demonstrates asymmetrical frontoparietal
      cortical atrophy in the later stages of the illness. Neuropathological
      examination reveals neuronal loss, gliosis and swollen achromatic neurons within
      the frontal and temporal cortices, and the substantia nigra. We discuss here a
      unique phenomenon not described so far in three patients with clinical features
      of CBD, one with subsequent autopsy observations. When awake, they all showed a
      common behavior, their mouth opened constantly and immediately, when a tongue
      depresser was approached in front of it by the examiner. In two of them, their
      mouth also opened when its corner was stroked by a tongue-depressor. They could
      not control these phenomena at all, even they were asked not to open their mouth.
      We would like to call these phenomena "forced mouth opening reactions" because
      they were uncontrollable voluntarily. They may be divided into two groups, i.e.
      visual and tactile "forced mouth opening reactions". In all the patients the
      neurological, neuro-imaging and neuropathological data showed that the frontal
      lobes were damaged. Additionally, they had some frontal lobe release signs such
      as forced grasping, forced groping, or alien limb sign. We would like to apply
      the mechanism for these release signs to the "forced mouth opening reactions".
      Thus, we speculate that the frontal lobe contains a higher motor control
      mechanism for normal mouth opening movement, and the "forced mouth opening
      reactions" result from impairment of this control.

PMID- 9248335
TI  - [Clinical and immunological findings of hepatitis B virus associated spastic
      paraparesis--a comparison with HAM].
AB  - We investigated clinical features and immunological parameters in 40 patients
      with slowly progressive spastic paraparesis including 13 cases (4 men and 9
      women, aged 43 to 71, mean 61 years) with positive antibody to hepatitis B virus
      (HBV), 13 (6 men and 7 women, aged 39 to 75, mean 63 years) with positive
      antibody to HBV and HTLV-I, and 14 (3 men and 11 women, aged 33 to 71, mean 55
      years) with positive antibody to HTLV-I (HAM). None showed obviously organic
      changes of the spine on magnetic resonance image. Patients with positive antibody
      to HBV (hepatitis B virus associated myelopathy, HBM) were significantly lower in
      disability grade and had a fewer incidence of micturition than in the HAM.
      Furthermore, natural killer (NK) activities were in normal range and peripheral
      blood lymphocytes did not show autologous proliferation response (APR). Patients
      with positive antibody to both HBV and HTLV-I showed APR similar to HAM, but in
      most patients NK activities were within normal range. These results suggest that
      the mechanism of myelopathy in HBM may be different from that in HAM, and HBV
      infection may play a role as a cofactor in HAM.

PMID- 9248336
TI  - [Endothelial cell activation and/or injury in multiple sclerosis: analysis with
      von Willebrand factor and thrombomodulin].
AB  - Breakdown of the blood-brain barrier, which consists of endothelial cells, is
      implicated essential in the pathogenesis of multiple sclerosis (MS). To examine
      the endothelial cell damage, we determined the von Willebrand factor and
      thrombomodulin, markers for endothelial cell activation and/or injury, in the
      peripheral blood of patients with MS. The subjects were 26 patients with
      relapsing-remitting MS and 35 control subjects (mean age +/- standard deviation,
      44.8 +/- 9.6 years). Patients with systemic vasculitis were excluded. The plasma
      activity of von Willebrand factor was significantly higher in patients with MS in
      the active phase (n = 23; 44.6 +/- 9.6 years) than in the age-matched controls.
      This suggests that von Willebrand factor could be a useful marker for evaluating
      the breakdown of blood-brain barrier resulting from endothelial damage in MS. In
      contrast, the serum level of thrombomodulin was not significantly different
      between patients with active MS and the controls. In MS patients (n = 15; 44.2 +/
      2.2 years), the plasma activity of von Willebrand factor was significantly
      lowered after immunosuppressive treatment. This suggests that von Willebrand
      factor could be used as a parameter for assessing the effect of treatment in MS.

PMID- 9248337
TI  - [An autopsied case of atypical presenile dementia which shows lobar atrophy,
      severe neurofibrillary tangles and calcification].
AB  - We report an autopsy case of atypical presenile dementia. Shibayama, Kosaka and
      others had reported similar autopsy cases. These cases had the following common
      pathologic characteristics: circumscribed cerebral atrophy, diffuse
      neurofibrillary tangles (NFTs) noted in the cerebral cortex with few senile
      plaques (SPs), and pathological calcification. We propose the term "dementia with
      cerebral calcification and tangles" (DCCT) for this atypical presenile dementia.
      Our patient, who was female and died at the age of 65 years, also exhibited these
      characteristics. Her clinical diagnosis was Alzheimer's disease. She had
      developed apparent dementia at the age of 55. Psychological and neurological
      symptoms such as memory impairment, speech disturbance and abnormal behavior
      slowly progressed. Gradually, she had become bedridden in her own home. When she
      was 65 years old, she was admitted because of pneumonia, and died soon after. In
      the pathologic examination of our patient, the brain weight was 850 g, and severe
      cerebral atrophy predominant in the temporal lobe was noted. Microscopically,
      diffuse and numerous NFTs were also found in the cerebral cortex and brain stem.
      Some NFTs were observed in the dentate nucleus of the cerebellum. However, SPs
      were seldom noted. Calcifications were also found in the putamen, globus pallidus
      and cerebellar cortex. NFTs in our case had developed without the formation of
      SPs. The degree of the NFT formation was correlated to the extent of cerebral
      cortical atrophy and neuron loss. Therefore, we suspect that NFTs with neuron
      loss strongly contribute to clinical symptoms such as dementia. The distribution
      of NFTs resembles that in patients with Alzheimer's disease, they are more
      prominent in the temporal lobe in our case. Although there has not been any
      discussion about the findings of glial cells and neuropils in DCCT, our detailed
      examination showed argyrophilic structures in glial cells and in neuropils. Most
      of the glial cells appeared to be oligodendrocytes. Calcification is also a
      prominent characteristic of DCCT. Using analytical electron microscopy, we
      examined the area of calcification in the globus pallidus and cerebellum, and
      found an accumulation of both Fe and Ca. The role of calcification in the
      pathogenesis, however, remains unclear. It is very important to examine cases of
      atypical presenile dementia clinicopathologically, in order to study the
      correlation between NFTs and SPs in neurological disease, and to understand their
      pathogenetic significance.

PMID- 9248338
TI  - [Idiopathic hypertrophic cranial pachymeningitis associated with Horner's
      syndrome. A case report].
AB  - A 64-year-old man was admitted to our hospital for recurrence of visual
      disturbance and double vision experienced 1 year previously. He was alert and
      oriented. Bilateral light perception in a vision test, the third to the sixth
      cranial nerve palsies on the left side, and neck stiffness were observed. The
      patient exhibited left blepharoptosis, anisocoria and a left miotic pupil. After
      a pupillary drug test, a diagnosis of Horner's syndrome was made. Laboratory
      tests revealed hypoalbuminemia, elevated erythrocyte sedimentation rate, positive
      rheumatoid factor, and elevated p-ANCA. Examination of the cerebrospinal fluid
      showed increased initial pressure and pleocytosis, but its bacterial and fungal
      cultures were negative. Cranial magnetic resonance imaging after intravenous
      administration of gadolinium revealed mild brain edema and marked hypertrophy of
      the left tentorium cerebelli, bilateral frontal dura and falx. Marked hypertrophy
      of the dura accompanied by cellular infiltration was observed in biopsied dura
      specimens. The patient was given a diagnosis as idiopathic hypertrophic cranial
      pachymeningitis (IHCP). His ocular symptoms gradually improved with
      methylprednisolone pulse therapy and oral prednisolone. This is the first
      reported case of IHCP associated with Horner's syndrome. Previous anatomical
      findings of the cavernous sinus suggest that Horner syndrome in this patient
      might be due to a mechanism other than constrictive compression of the cranial
      nerves by the hypertrophic dura mater.

PMID- 9248339
TI  - [A case report of mixed transcortical aphasia due to three attacks of cerebral
      infarction].
AB  - This is a case report of a 69-year-old right handed male patient with mixed
      transcortical aphasia caused by the three consecutive strokes in the left
      hemisphere. The initial attack affected the left occipital region and the second
      one influenced the angular region of the left parietal lobe. After the second
      attack the patient showed a symptom similar to transcortical sensory aphasia,
      although the prognosis was good. The third stroke attacked the subcortical region
      of the left middle frontal gyrus, consequently the patient became severe mixed
      transcortical aphasic who could only repeat. Even two years after the last stroke
      the aphasia was hardly improved. These symptoms are considered to be caused by
      "functional isolation" of the affected anterior-posterior language areas and the
      fasciculus arcuatus.

PMID- 9248340
TI  - [Successful direct thrombolysis in a patient with extensive dural sinus
      thrombosis induced by danazol].
AB  - A 43-year-old woman was suffered from an increasing headache with nausea and
      vomiting for nine days. She had received danazol 400 mg daily for endometriosis
      last two months. CT scan and neurological examinations revealed no evidence of
      abnormality. MRI showed isosignal intensity on T1-weighted images and high signal
      intensity on T2-weighted images in the superior sagittal, right transverse,
      sigmoid and straight sinuses suggesting thrombosis. With angiography, we
      confirmed extensive dural sinus thrombosis in the superior sagittal, straight,
      right transverse and sigmoid sinuses. She, then, developed progressing
      neurological deterioration with dysarthria and drowsy. Microcatheter was placed
      directly into the thrombus at dural sinus via transfemoral route. Thrombolytic
      therapy with urokinase was performed in right transverse, confluens sinuum,
      superior sagittal and straight sinuses. Successful recanalization with remarkable
      improvement of symptoms was achieved except right transverse sinus. We believe
      danazol played a role in the occurrence of dural sinus thrombosis. MRI and MRV
      were noninvasive and useful for diagnosis and follow-up of dural sinus
      thrombosis. Direct thrombolysis should be considered for dural sinus thrombosis,
      especially when clinical symptoms are rapidly deterioration with conventional
      anticoagulant therapy.

PMID- 9248341
TI  - [A case of Ki-1 lymphoma-associated eosinophilic polymyositis].
AB  - We report on a patient of Ki-1 lymphoma-associated hypereosinophilic syndrome and
      eosinophilic polymyositis. A 22-year-old male was admitted to a hospital because
      of anterior chest pain, when he had a white cell count of 12,000 with 33% of
      eosinophils. He first noticed muscle weakness in the right shoulder at age 23
      years. At the age of 25, he experienced marked muscle weakness in his arms and
      neck, which brought him to our hospital. Neurological examination on admission
      revealed moderate muscle atrophy and weakness in the neck flexors and both upper
      extremities, and marked muscle hypertrophy in the sternocleidomastoideus and
      trapezius muscles. Laboratory studies showed a white blood cell count of 17,700
      with 56% of eosinophils. His serum creatine kinase (CK) level was elevated to 347
      units. A muscle biopsy specimen showing active myositis infiltrated by
      eosinophils confirmed the diagnosis of eosinophilic myositis. Although
      eosinophilia and serum CK activity decreased markedly with corticosteroid
      treatment, his muscle weakness was unchanged. At the age of 27 years,
      lymphadenopathy developed. Immunocytochemical examination on a biopsied neck
      lymph node indicated Ki-1 lymphoma with positive Ki-1, CD45 and epithelial
      membrane antibodies. In spite of chemotherapy and local irradiation treatment, he
      died four months after the emergence of Ki-1 lymphoma. We discussed the
      relationship between hypereosinophilic syndrome, eosinophilic polymyositis and Ki
      1 lymphoma on pathogenetic mechanism.

PMID- 9248342
TI  - [Left hand clumsiness due to disturbance of kinesthesia after damage to the
      dorsal column of the high cervical cord].
AB  - We described a 48-year-old, right-handed woman who manifested left hand
      clumsiness after damage to the dorsal column of the high cervical cord due to
      probable multiple sclerosis. On February 29, 1996, she developed a weakness in
      the right limbs. Subsequently, she suffered numbness and clumsiness in the left
      limbs, even though muscle strength of the left limbs was preserved. Seventeen
      days later, she was referred to our hospital. A T2-weighted MRI after admission
      demonstrated high signal intensities in the left dorsal column and the right
      antero-lateral part of the cervical cord at the C1 to C3 vertebral level. Under
      the diagnosis of probable multiple sclerosis, steroid pulse therapy was applied
      twice and she gradually regained muscle strength in the right limbs and sensation
      in the left limbs. One month later, elemental sensations such as pain, touch,
      temperature, vibration, and position, as well as discriminative sensations such
      as localization sensation, two-point discrimination, barognosis, pinch-press
      discrimination, and graphesthesia in the left limbs returned to normal. However,
      her left hand remained clumsy, especially when she tried to manipulate objects.
      She also showed a great difficulty in sustaining a constant level of pinching
      force by the left thumb and index finger, and in localizing her right thumb
      placed in space with the left hand with her eyes closed. She stated herself that
      she could not sense at all how her left hand and fingers were moving.
      Somatosensory evoked potentials recorded from the right scalp showed that the NI
      was poorly organized and the patency of subsequent peaks was delayed.
      Transcranial magnetic stimulation revealed that the pyramidal tract from the
      right motor cortex to the left cervical cord was functionally intact. These
      observations lead us to conclude as follows: (1) the patient's left hand
      clumsiness is probably due to the disturbance of kinesthesia, which is crucial to
      activate temporo-spatial patterns of complex hand and finger movements as well as
      to maintain long sequences of simple motor execution without vision; and (2)
      kinesthesia is a specific sensation that is presumably conveyed by the dorsal
      columns and could be selectively affected by a cervical cord lesion.

PMID- 9248343
TI  - [A case of mitochondrial encephalomyopathy showing ophthalmoplegia, diabetes
      mellitus and hearing loss associated with the A3243G mutation of mitochondrial
      DNA].
AB  - We report a 47-year-old female patient showing clinical features of chronic
      progressive external ophthalmoplegia (CPEO) without stroke-like episodes. Large
      scale deletion of mitochondrial DNA (mtDNA) was not found in her biopsied muscle,
      whereas the A-->G transition at position 3243 (A3243G) was detected. The
      patient's mother had diabetes mellitus, suggesting maternal inheritance. This
      mutation is usually associated with MELAS, but wide clinical variety of the
      mutation has been recognized. Although several patients of CPEO with A3243G
      mutation (CPEO3243) have been found in the Western countries, only one case has
      been reported in detail in Japan. The CPEO3243 patients, including ours, show
      retinopathy less frequently, but diabetes mellitus and hearing loss more
      frequently than CPEO patients with deletions of mtDNA (CPEO delta). CPEO3243 is
      usually inherited maternally, but almost all CPEO delta is sporadic. With regard
      to COX activity of biopsied muscles, CPEO3243 resembles CPEO delta more than
      MELAS3243. This suggests that how the mutant mtDNA is distributed among cells or
      tissues may have more significant effect on clinical phenotype than what type of
      mtDNA mutation exists. The presence of such a CPEO3243 patient like ours could be
      an important suggestion toward further understanding of mitochondrial diseases.

PMID- 9248344
TI  - [A case of Guillain-Barre syndrome with bulbar palsy and a high titer of anti
      GT1a antibody].
AB  - We report a rare case of Guillain-Barre syndrome (GBS) in a patient with anti
      GT1a antibody. A 42-year-old man was admitted with dysphagia, dysarthria and
      weakness in his neck and both upper limbs. Serial electrophysiological studies
      suggested that the predominant process was demyelination of the motor nerves.
      Thin-layer chromatography with immunostaining revealed that his serum IgG reacted
      strongly with GT1a and weakly with GQ1b. He recovered rapidly with
      plasmapheresis. These findings suggest that anti-GT1a IgG antibody might play an
      important role in the pathogenesis of bulbar palsy in GBS.

PMID- 9248345
TI  - [A case report of alternating abducens hemiplegia with special reference to the
      supranuclear pathway to the facial nucleus].
AB  - A case of alternating abducens hemiplegia was reported. A 16-year-old girl
      developed alternating hemiplegia characterized by the left abducens nerve palsy
      and right hemiparesis. In addition, she had right supranuclear facial nerve
      palsy. A brain MRI showed left mid to lower pontine lesion and vertebral
      angiography revealed medullary venous malformation in the left pons. SEP with
      right posterior tibial nerve stimulation showed a delayed central conduction
      time, suggesting that the lesion involved left medial lemniscus. We previously
      reported a 39-year-old man who developed pure alternating abducens hemiplegia. He
      did not show supranuclear facial nerve palsy or SEP abnormality. These findings
      support the idea that the supranuclear facial nerve fiber leaves the pyramidal
      tract at the upper to middle pons and descends in the area of the pontine
      tegmentum around the medial lemniscus.

PMID- 9248346
TI  - [Creutzfeldt-Jakob like syndrome due to lithium intoxication--a case report].
AB  - A woman with mania who had been treated with lithium carbonate since 69 years of
      age presented mild tremulousness of both hands at the age of 76 years. She
      subsequently developed dysphagia, dysarthria, unsteady gait and progressive
      deterioration of the higher cortical function over 1.5 months. Her tremulousness
      deteriorated until it resembled myoclonus. EEG showed periodic sharp wave
      complexes appearing predominantly over the bilateral parieto-occipital areas.
      Although the EEG abnormality was not identical with that usually observed in the
      fully developed stage of Creutzfeldt-Jakob disease (CJD), it was reminiscent of
      that seen in the early stage of CJD. Thus, her clinical symptoms and signs were
      considered to resemble those of CJD. The plasma concentration of lithium,
      however, was found to be over the therapeutic range. Reduction of the dose of
      lithium carbonate almost completely resolved her symptoms within 3 weeks.
      Consequently, her clinical condition was considered lithium intoxication.
      Antidepressant and bismuth as well as lithium have been reported to induce a
      Creutzfeldt-Jakob like syndrome. Awareness of drug-induced Creutzfeldt-Jakob like
      syndrome is clinically important because of its excellent prognosis as opposed to
      the ominous prognosis of CJD.

PMID- 9248347
TI  - [A case of tabes dorsalis observed in an HTLV-1 carrier].
AB  - We report a case of a 53-year-old female HTLV-1 carrier with tabes dorsalis. In
      addition to typical symptoms of tabes dorsalis, she presented HTLV-1 associated
      myelopathy (HAM) like clinical features such as sensory disturbance with thoracic
      sensory levels and bladder disturbance (pollakiuria). Although penicillin
      treatment did not improve in her neurological symptoms, steroid therapy was
      effective especially in HAM like symptoms. The CSF neopterin level was markedly
      decreased after steroid therapy, indicating that inflammation in the spinal cord
      was settled down after treatment. Our case suggests that CNS infection like tabes
      dorsalis may be modified by HTLV-1 infection and then present some atypical
      clinical features based upon altered immunological aspects of HTLV-1 carriers.

PMID- 9248348
TI  - [Pupillary abnormalities in a patient with clinically diagnosed corticobasal
      degeneration].
AB  - We report a 65-year-old woman, who suffered from clumsiness of the left hand for
      6 years. Gait disturbance, body balance impairment and rigidity of the left arm
      appeared progressively. Anti-parkinsonian drugs such as 1-dopa, doroxidopa,
      amantadine and bromocriptine were ineffective. Magnetic resonance imaging showed
      brain atrophy, especially in the right fronto-parietal lobes. Positron emission
      tomography (18F-fluoro-2-deoxy-D-glucose) showed decreased glucose metabolism in
      the right cerebral cortex, putamen and thalamus. A diagnosis of corticobasal
      degeneration was made, based on the clinical manifestations, MRI and PET
      findings. She also showed anisocoria, vertical gaze palsy and abnormal pupillary
      reactions. Her left pupil showed an oval figure shifted from the center position.
      The pupils exhibited denervation supersensitivity in the 0.125% pilocarpine test.
      We consider that her pupillary abnormalities may be related to her midbrain
      lesion (midbrain corectopia) associated with corticobasal degeneration.

PMID- 9248349
TI  - [A case of isolated ACTH deficiency accompanied by generalized painful muscle
      cramp].
AB  - We report a patient who had generalized painful muscle cramps associated with
      isolated ACTH deficiency. A 68-year-old woman was hospitalized because of painful
      muscle cramps present for one year. Neurological examination revealed no
      abnormalities except for generalized painful muscle cramps. Serum electrolyte and
      CPK levels were normal. Serum ACTH and cortisol levels as well as urine 17-OHCS
      were low. An ACTH loading test employing insulin, TRH and LH-RH indicated
      isolated ACTH deficiency. Just after the muscle cramp, EMG revealed a low
      amplitude in the biceps muscle. Colon biopsy showed mild fibrosis and
      inflammatory cell infiltration in the lamina propria. Her muscle cramps improved
      markedly after two weeks of hydrocortisone replacement therapy and resolved after
      three weeks, suggesting that this symptom was closely related to isolated ACTH
      deficiency. Our case suggests that isolated ACTH deficiency may present with very
      similar clinical symptoms to Satoyoshi disease.

PMID- 9248351
TI  - [Synthetic 2-amino alcohol derivatives as chiral auxiliaries].
AB  - Both enantiomers of cis-4,5-disubstituted 2-oxazolidinones, DHAOx (4,5-(9,10
      dihydroanthraceno)oxazolidin-2-one), DMAOx (4,5-(9,10-dihydro-9,10
      dimethylanthraceno)oxazolidin-2-one) , CPAOx (4,5-(1,4-cyclopentano)oxazolidin-2
      one), HMCOx (4,5-[3,5-(1,2,3,4,4,5-hexamethyl-1,4-cyclopenteno)]-oxaz olidin-2
      one) and BPSOx (4,5-[1,4-(2-tert-butyldiphenylsilyloxy)cyclopenteno]oxazoli dine
      2-one), which are sterically congested and conformationally fixed by
      bicyclo[2.2.1] and [2.2.2] ring systems are newly prepared by the Diels-Alder
      reactions of 2-oxazolone with the cyclic dienes such as anthracenes and
      cyclopentadienes followed by optical resolution with MAC acid (2-methoxy-1
      apocamphanecarboxylic acid). These compounds, particularly DMAOx, HMCOx and
      BPSOx, serve well as the most powerful 2-oxazolidinone chiral auxiliaries
      reported so far for the asymmetric reactions such as alkylations, the Diels-Alder
      reactions, the Michael-type additions and aldol reactions. Sterically congested 2
      aminoalcohol derivatives derived from the ring-opening of these 2-oxazolidinones
      are shown to be highly useful auxiliaries for enantioselective additions of
      diethylzinc to aldehydes and enantiodivergent conversion of meso-dicarboxylic
      anhydrides to chiral half-esters.

PMID- 9248350
TI  - [Present status of Lyme borreliosis and characterization of Lyme disease Borrelia
      isolated in Japan].
AB  - Lyme disease is a multisystemic disorder caused by infection with Borrelia
      burgdorferi sensu lato which is carried by ticks of the Ixodes ricinus complex.
      The agent was discovered in 1982 in North America and the disease is recognized
      as an emerging infectious diseases in North America and Europe. Japanese Borrelia
      isolates were characterized by genetic and immunologic analysis. Isolates from
      Ixodes ovatus were found to be unique by DNA/DNA hybridization analysis,
      restriction fragment length polymorphism analyses of the flagellin gene and the
      16S rRNA genes, and were described as new species, Borrelia japonica. Isolates
      from Ixodes persulcatus were determined as Borrelia garinii and Borrelia afzelii.
      However, B. garinii found in Japan was different from those from Europe in
      immunologic and genetic characteristics of outer surface protein A, but B.
      afzelii isolates from Japan and Europe were identical. An experimental model of
      arthritis related to Lyme disease using outbred ddY mice was established. Whole
      cell vaccine prepared from North American and European isolates could not elicit
      protective immunity against infection of Japanese isolates. This implies that
      vaccine development using Japanese isolates is necessary. Borrelia bound
      specifically to galactosylceramide (GalCer), glucosylceramide and
      lactosylceramide which are present in various types of cells as binding receptor,
      but not to other glycosphingolipids. Furthermore, the infectivity of Borrelia may
      be associated with the binding to glycosphingolipids on the cell surface and a 67
      kilodalton protein of Lyme disease Borrelia may be involved in binding of
      Borrelia to GalCer.

PMID- 9248352
TI  - [Weitz' aminium salt initiated electron transfer reactions and application to the
      synthesis of natural products].
AB  - A stable cation radical Weitz' aminium salt, tris(4-bromophenyl)aminium
      hexachloroantimonate (BAHA) initiated electron transfer has been found to
      efficiently promote a great variety of reactions on electron-rich substrates:
      e.g. the cation radical pericyclic reactions, the chain-induced cation radical
      oxygenation of strained olefines and dienes, and several other intriguing
      reactions on a great variety of electron-rich substrate. The discovery of the
      Weitz' aminium salt catalysed Diels-Alder reaction has stimulated interest in
      cation radical chemistry and facilitated the development of a wide range of
      cation radical pericyclic chemistry. Applications of the method to the synthesis
      of natural products utilizing BAHA are also presented. Reaction of a lignan
      precursor, cinnamyl alcohols with BAHA in tetrahydrofuran (THF) gave a furofuran
      lignan, (+/-)-sesamin in one step. Podophyllum lignans, (+/-)-isopodophyllotoxin
      and (+/-)-isopicropodophyllin were synthesized by a biomimetic procedure from the
      doubly unsaturated esters by means of the BAHA induced cation-radical
      cycloaddition reaction. A new general synthesis for (+/-)-dibenzocyclooctadiene
      lignans was established utilizing novel synthetic method for quinone derivatives
      by oxidation with BAHA. Reactions of phenol derivatives using BAHA gave the
      corresponding quinone derivatives, which may be useful synthon for obtaining
      quassinoids such as quassin.

PMID- 9248353
TI  - [Development of a silicon-mediated [3 + 2] annulation and its application to the
      synthesis of natural products].

PMID- 9248354
TI  - Anger coping styles and perceived social support.
AB  - This study was based on the hypothesis that perceived availability of social
      support, independent of the influence of social desirability, would be inversely
      related to both anger-in and anger-out coping styles. Participants were 101
      college-aged Caucasians in the Northeast. In a regression analysis, the anger
      coping scales together accounted for 9% of the unique variance in total social
      support. Anger-in, but not anger-out, was a significant predictor of social
      support independent of the effects of social desirability. In addition, anger-in,
      independent of response bias, was inversely related to deficiencies in appraisal
      support, self-esteem support, tangible support, and belongingness support. These
      findings were interpreted in the context of the psychosocial vulnerability model
      of disease risk, which suggests that deficits in perceived social support may
      represent a diathesis for ill health among individuals exhibiting an anger
      suppression coping style.

PMID- 9248355
TI  - A comparison of updating and explanation as causes of the incongruity effect on
      person memory.
AB  - Information that is incongruent with a prior expectancy is remembered better than
      congruent information. Two explanations were investigated: (a) people attempt to
      explain incongruent information to understand it, and (b) people use incongruent
      information to update their expectancies. The common assumption in these two
      accounts is that the additional cognitive processing stimulated by incongruent
      information is responsible for the incongruity effect. In this study, U.S.
      students were explicitly requested to engage in one or the other of these
      processes. Although both processes resulted in an incongruity effect, there was a
      positive correlation between recall of expectancy-congruent and expectancy
      incongruent items in the impression-updating condition but not in the other
      condition; those in the impression-updating condition showed greater expectancy
      change.

PMID- 9248356
TI  - Suspiciousness, mental simulation, and norm theory.
AB  - Seven studies were conducted to replicate the work of Miller, Turnbull, and
      McFarland (1989), who tested predictions from norm theory (Kahneman & Miller,
      1986). The first three studies with stimulus materials identical to those used by
      Miller et al. failed to confirm that the ease with which the event might be
      mentally simulated affected the degree of suspiciousness. In Studies 4, 5, and 6,
      the improbable events were made objectively more probable, but this did not
      produce significant results. In the 7th study, the objective probability and
      attitude toward the target were varied. Although there was a main effect for ease
      of mental simulation, this effect was produced by only 1 of the 3 vignettes.

PMID- 9248357
TI  - Awareness of interpersonal style and self-evaluation.
AB  - Interpersonal theorists assume that the greater the discrepancy between a
      person's own assessment of his or her interpersonal style and the perceptions of
      others, the greater will be that individual's reported psychological distress. In
      the present study, 32 U.S. undergraduate students, all female, completed the
      Interpersonal Checklist (ICL) of LaForge and Suczek (1955) to measure their
      interpersonal styles and the Symptom Distress Checklist-Revised (SCL-90-R) of
      Derogatis (1983) to measure their psychological distress. On the basis of their
      ICL scores, they were placed with complementary partners of the same sex to
      interact for 7 min. Verbal transcripts and soundless videotapes were prepared
      from the videotapes of their interactions. After either reading the verbal
      transcript or watching the soundless videotape, raters completed an ICL
      describing the impression each participant was communicating. When, on the basis
      of either the videotape or the transcript, raters judged a participant as more
      dominant than the participant judged herself, the discrepancy was significantly
      related to SCL-90-R scale scores on Positive Symptom Total, Global Severity
      Index, Interpersonal Sensitivity, Anxiety, and Depression. The results supported
      the assumption that self-other discrepancy was associated with psychological
      difficulties, especially when the discrepancy involved participants believing
      themselves less dominant than others perceived them.

PMID- 9248358
TI  - Explanatory style, family expressiveness, and self-esteem among Asian American
      and European American college students.
AB  - Fifty-nine Asian American and 40 European American college students completed
      questionnaires measuring explanatory style, family expressiveness, and self
      esteem. In both groups, a global explanatory style correlated with low self
      esteem, but only among European Americans was an internal style associated with
      low self-esteem. The two groups differed in reported styles of family
      expressiveness, with Asian Americans indicating more emotional restraint. The
      participants who reported more negative submissiveness had a more global
      explanatory style, whereas those who reported more positive dominance had a less
      global explanatory style. An additional measure developed to assess attribution
      to collectivities did not distinguish the two groups. Results were discussed in
      terms of the cross-cultural generality of the learned helplessness reformulation.

PMID- 9248359
TI  - Using cooperative learning to enhance the academic and social experiences of
      freshman student athletes.
AB  - One hundred seven freshman student athletes in 17 different women's and men's
      intercollegiate sports were required to attend evening study sessions. The
      student athletes completed academic assignments and studied for tests primarily
      in cooperative learning groups. As gauges of the program's impact on the
      participants, 3 questionnaires were administered to a sample of 50 (25 women and
      25 men). The respondents reported that (a) they worked cooperatively on academic
      assignments, (b) the program staff provided both academic and personal support
      while structuring and facilitating cooperative learning groups, and (c) they
      themselves were highly task oriented, confident of their academic ability, and
      involved in positive and supportive relationships with their fellow participants.

PMID- 9248360
TI  - Culture and spontaneous self-concept among Filipino college students.
AB  - Responses of 157 Filipino college students to the Twenty Statements Test (TST)
      were analyzed for content and compared with earlier responses to the TST by U.S.
      and Hong Kong Chinese college students. Despite the supposedly collectivist
      nature of the Filipino culture, far fewer Filipino students than U.S. and Hong
      Kong Chinese students described themselves in terms of social roles. Contrary to
      theoretical claims, the Filipinos made greater use of the global identity
      category than did either the U.S. or Hong Kong Chinese students. Evidence also
      supported the cross-cultural validity of 4 of the Big Five (McCrae & Costa, 1988)
      personality traits. However, there are questions about the relevance of Openness
      to Experience to any of these three cultures. Moreover, the finding that the
      Filipino respondents reported a higher percentage of positive self-descriptions
      than did either the U.S. or Chinese respondents indicated that such differences
      cannot be explained in terms of the individualism-collectivism dimension.

PMID- 9248362
TI  - Helping behaviors and the perception of helping intentions among Chinese
      students.
AB  - A questionnaire survey explored the kinds of helping behaviors given and received
      by Chinese college students and the kinds of explanations offered for these
      behaviors. Helping behaviors reported by the Chinese students paralleled those of
      U.S. college students in McGuire (1994); the behaviors were sorted, according to
      her typology, into casual, substantial personal, emotional, and emergency
      helping. Four categories of perceived intentions behind helping behaviors were
      identified: altruistic, normative, relationship, and exchange.

PMID- 9248361
TI  - Parenting of young children by fathers in Mexico and the United States.
AB  - In the present study, the parenting practices and developmental expectations were
      examined in a sample of 96 fathers from Mexico and the United States, all with
      children from 1 to 5 years of age. The selection of fathers from both countries
      was controlled for the family's socioeconomic status (SES) and for the age and
      gender of their children. The Parent Behavior Checklist, a 100-item rating scale
      was used to measure parents' developmental expectations and their discipline and
      nurturing practices. According to the results, Mexican and U.S. fathers did not
      differ significantly in their developmental expectations or parenting practices.
      In both countries, fathers from lower SES families were less nurturing and used
      more frequent discipline than fathers from higher SES families.

PMID- 9248363
TI  - Religiosity and sphere-specific just world beliefs in 16- to 18-year-olds.
AB  - One hundred forty-three (31 female and 112 male) English school pupils, 16 to 18
      years old, completed the Francis Scale of Attitudes towards Christianity (FSAC;
      Francis & Stubbs, 1987), the Global Belief in a Just World Scale (GBJWS; Lipkus,
      1991), and the Multidimensional Belief in a Just World Scale (MBJWS; Furnham &
      Procter, 1992). The MBJWS yields three subscale scores: Sociopolitical Just World
      Beliefs (SJW), Interpersonal Just World Beliefs (IJW), and Personal Just World
      Beliefs (PJW). Scores on the FSAC were not associated with scores on the GBJWS,
      the SJW, or the IJW, but they were positively associated, albeit weakly, with
      scores on the PJW.

PMID- 9248365
TI  - Practice teachers' responses to a suicidal student.

PMID- 9248364
TI  - Self- and peer-ratings of female and male roles and attributes.

PMID- 9248366
TI  - Body burden measurements and models to assess inhalation exposure to methyl
      tertiary butyl ether (MTBE).
AB  - Biomarkers of methyl tertiary butyl either (MTBE) exposure and the partitioning
      of inhaled MTBE into the body were investigated in a human chamber study. Two
      subjects were exposed to an environmentally relevant nominal 5,011 micrograms/m3
      (1.39 ppm) MTBE for 1 hour, followed by clean-air exposure for 7 hours. Breath
      and blood were simultaneously sampled, while total urine was collected at
      prescribed times before, during, and after the exposure. Mass-balance and
      toxicokinetic analyses were conducted based upon the time series measurement of
      multiple body-burden endpoints, including MTBE in alveolar breath, and MTBE and
      tertiary butyl alcohol (TBA) in venous blood and urine. The decay of MTBE in the
      blood was assessed by fitting the post-exposure data to a 2- or 3-exponential
      model that yielded residence times(tau) of 2-3 min, 15-50 min, and 3-13 h as
      measured by alveolar breath, and 5 min, 60 min, and 32 h as evaluated from venous
      blood measurements. Based on observations of lower than expected blood and breath
      MTBE during uptake and a decreasing blood-to-breath ratio during the post
      exposure decay period, we hypothesize that the respiratory mucous membranes were
      serving as a reservoir for the retention of MTBE. The decay data suggest that 6
      9% of the MTBE intake may be retained by this non-blood reservoir. The
      compartmental modeling was further used to estimate important parameters that
      define the uptake of inhaled MTBE. The first of these parameters is f, the
      fraction of C(air) exhaled at equilibrium, estimated as 0.60 and 0.46 for the
      female and male subject, respectively. The second parameter is the blood-to
      breath partition coefficient (P) estimated as approximately 18. The product of
      these parameters provides an estimate of the blood concentration at equilibrium
      as 8-11 times the air concentration. Blood TBA lagged MTBE levels and decayed
      more slowly (tau = 1.5-3 h), providing a more stable indication of longer term
      integrated exposure. The concentration ranges of MTBE and TBA in urine were
      similar to that of the blood, ranging from 0.37 to 15 micrograms/L and 2 to 15
      micrograms/L, respectively. In urine, MTBE and TBA by themselves bore little
      relationship to the exposure. However, the MTBE:TBA ratio followed the pattern of
      exposure, with peak values occurring at the end of the exposure (20- and 60-fold
      greater than pre-exposure values) before decaying back to pre-exposure levels by
      the end of the 7-h decay period. Urinary elimination accounted for a very small
      fraction of total MTBE elimination (< 1%).

PMID- 9248367
TI  - Identification of an accurate soil suspension/dispersion modeling method for use
      in estimating health-based soil cleanup levels of hexavalent chromium in chromite
      ore processing residues.
AB  - The primary health concern associated with chromite ore processing residues
      (COPR) at sites in Hudson County, NJ, is the inhalation of Cr(VI) suspended from
      surface soils. Since health-based soil standards for Cr(VI) will be derived using
      the inhalation pathway, soil suspension modeling will be necessary to estimate
      site-specific, health-based soil cleanup levels (HBSCLs). The purpose of this
      study was to identify the most appropriate particulate emission and air
      dispersion models for estimating soil suspension at these sites based on their
      theoretical underpinnings, scientific acceptability, and past performance. The
      identified modeling approach, the AP-42 particulate emission model and the
      fugitive dust model (FDM), was used to calculate concentrations of airborne
      Cr(VI) and TSP at two COPR sites. These estimated concentrations were then
      compared to concentrations measured at each site. The TSP concentrations
      calculated using the AP-42/FDM soil suspension modeling approach were all within
      a factor of 3 of the measured concentrations. The majority of the estimated air
      concentrations were greater than the measured, indicating that the AP-42/FDM
      approach tends to overestimate on-site concentrations. The site-specific Cr(VI)
      HBSCLs for these two sites calculated using this conservative soil suspension
      modeling approach ranged from 190 to 420 mg/kg.

PMID- 9248368
TI  - Promote collaboration. Break down the barriers.

PMID- 9248369
TI  - Urinary continence changes after hip-fracture repair.
AB  - Hip fractures can adversely affect an older adult's functional well-being. Little
      is known about the changes in continence status after hip-fracture repair. To
      investigate postoperative complications, the authors reviewed a convenience
      sample of 100 medical records of adults ages 55 years and over who were admitted
      to two metropolitan Baltimore hospitals for surgical repair of a fractured hip.
      There were data regarding postoperative incontinence for 95 individuals.
      Prevalence of urinary incontinence significantly increased from the preoperative
      rate of 20% to 43% postoperatively. That is, 19 individuals were incontinent
      preoperatively, and 41 individuals were incontinent postoperatively. Two
      individuals who had been incontinent preoperatively became continent
      postoperatively. Men were more likely to become incontinent than women, as were
      cognitively impaired individuals compared to cognitively intact individuals.

PMID- 9248370
TI  - Outcomes of individualized interventions in patients with severe eating
      difficulties.
AB  - The aim of this case study is to describe the outcomes of individualized
      interventions for patients with severe eating difficulties. The participants were
      15 patients who had severe eating difficulties following a stroke or brain tumor
      and were receiving oral feeding or tube feeding. Interventions focused on
      training functions needed for eating, activities in eating, and discussions with
      the patient. Improvements were especially noted in eating activities, and some
      improvements were noted in oral movements and nutritional status. Before the
      interventions, none of the patients ate regular food; afterward, six did, and in
      four patients, the feeding tube was removed. The patients said eating was easier,
      and they could eat in a safe way. Furthermore, they appreciated the attention to
      their experience during meals. Although the impairments were not always
      alleviated, the patients found means to cope with their eating difficulties.

PMID- 9248371
TI  - Predicting patients' deterioration and recovery.
AB  - The purpose of this study was to identify patient cues that expert nurses
      identify as a patient moves to/from deterioration and/or recovery. The sample of
      33 nurses was drawn from a medical intensive care unit (MICU). Data were
      collected through interviews regarding nurses' knowledge about caring for
      patients with acute gastrointestinal bleeding, heart failure/post-myocardial
      infarction, and pulmonary edema. Using the constant comparative technique, cues
      were identified and grouped into early, imminent, and late patterns for
      deterioration and into categories of early, midway, and complete for recovery.
      Rationales for the nurses' decisions included memories of patients with similar
      cues, using multiple not single cues, and clustering both physiological and
      psychological cues together. This study is a beginning effort toward validating
      nurses' intuitiveness and provides knowledge about expert practice that can be
      taught to novice practitioners and incorporated into protocols for care.

PMID- 9248372
TI  - Nurses' reactions to participation in cardiopulmonary resuscitation on the
      nursing unit.
AB  - A wide range of emotions are associated with cardiopulmonary resuscitation (CPR)
      attempts. Articles documenting nurses' reactions to CPR situations are scarce in
      the nursing literature. This study contains nurses' own descriptions of feelings
      experienced during and after CPR attempts and the nurses' suggestions for what
      could make the experience easier, what makes it more difficult, and what
      interventions the nurses use to reconcile their emotions. The participants were
      29 registered nurses employed at an urban Midwestern hospital who completed an
      open-ended questionnaire that elicited descriptions of CPR events. The data were
      analyzed using a process of thematic analysis.

PMID- 9248373
TI  - Becoming a father to a stillborn child.
AB  - The purpose of this study was to identify and describe the reaction of fathers to
      a stillborn child. Because little research has been done on this topic, an
      exploratory descriptive study was conducted. Eight fathers who had experienced a
      stillborn child were interviewed in-depth within the first 5 years following the
      death. Although the fathers exhibited grief reactions and behaviors such as
      shock, denial, anger, and acceptance, it was evident that taking on a fathering
      role was of central importance. The basic social process that the fathers in this
      study experienced was becoming a father to the stillborn child. The fathers were
      trying to assume a fathering role while they were grieving the death of their
      child. Understanding the process of becoming a father to a stillborn child is of
      value to health care professionals when considering ways to help fathers who have
      experienced such a loss.

PMID- 9248374
TI  - A comparison of three oral care products commonly used in practice.
AB  - This project compared the efficacy, patient satisfaction, and cost of three
      commonly used oral care products: lemon glycerin swabs, Moi-Stir swabs, and
      toothettes (pink sponge applicators) and water. Hospitalized adults who were
      either required to receive nothing by mouth or who required oxygen were asked to
      participate in the project. Once enrolled, the patients were randomly assigned to
      one of the three oral care groups. Oral assessments were performed daily, and
      perceptions of oral comfort were solicited from alert patients. Although the
      sample size was not large enough to reach statistical significance, a few trends
      were noted. First, the patients' oral condition generally worsened during the
      first 3 days but then improved between Days 4 and 5. Moi-Stir performed better
      than either lemon glycerin or toothettes and water, as evidenced by lower Day 4-5
      scores. Patients generally liked the swab to which they were assigned.

PMID- 9248375
TI  - Identifying denial in stroke patients.
AB  - The purpose of this study was to test the reliability of an experimental
      assessment tool for identifying and differentiating between psychodynamic and
      neurogenic denial in stroke patients. A one-page criterion referenced denial
      assessment tool was used by interdisciplinary rater teams to evaluate patients
      with either right or left hemisphere insults. High interrater reliability was
      obtained. Assessment data indicated that right-CVA patients had higher
      psychodynamic and neurogenic denial scores than left-CVA patients. Higher
      psychodynamic denial scores were also observed in the second month post-stroke.
      The experimental denial assessment tool proved to be a practical way for
      identifying and differentiating psychodynamic and neurogenic forms of denial.
      This tool can provide a means for ongoing assessment to support precise nursing
      diagnoses and promote effective patient-focused care planning throughout the
      rehabilitation process.

PMID- 9248376
TI  - Control of vascular complications after cardiac catheterization: a research-based
      protocol.
AB  - Cardiac catheterization has become a common diagnostic procedure. However, many
      institutions arbitrarily decide the postprocedure method used to achieve
      hemostasis, the approach to femoral site care, the patient's position while on
      bedrest, and the length of bedrest. The authors review past research studies and
      present a research-based protocol for postcatheterization nursing care.

PMID- 9248377
TI  - Prone positioning for the ARDS patient.
AB  - Various strategies have been tested in attempts to improve gas exchange in
      patients with Acute Respiratory Distress Syndrome (ARDS). However, it appears
      that the simple non-invasive act of prone positioning of the critically ill ARDS
      patient may improve gas exchange while preventing potential complications of high
      positive end expiratory pressure (PEEP), volutrauma, and oxygen toxicity.

PMID- 9248378
TI  - Near death experiences: critical care nurses' attitudes and interventions.
AB  - A patient is successfully resuscitated after a trauma or serious illness. It is
      increasingly common for such a patient to report having experienced a feeling of
      calm and peace, a feeling of being separated from the body, and/or a sense of
      moving through a dark tunnel ending at a bright light. Such experiences are known
      as near death experiences. What are critical care nurses to make of such accounts
      reported to them by their patients? This article explores critical care nurses'
      interests in, knowledge of, and attitudes towards the near death experience, and
      it identifies nursing interventions that critical care nurses can use during and
      after the patient experiences near death.

PMID- 9248379
TI  - Pathophysiology of fever. Part 1: The role of cytokines.
AB  - Because of advanced molecular physiology techniques, there is new information
      about how fever affects the body. Now, fever is identified as a cascade of
      physiologic events, not just a single symptom. This article, the first in a set
      of two on the physiology of fever, focuses on the role of cytokines as the
      trigger for the physiologic cascade of fever. (Watch for Part 2 in the next issue
      of DCCN, which challenges the assumption that cooling interventions are
      appropriate for all febrile patients.

PMID- 9248380
TI  - Integrating the acute care nurse practitioner into clinical practice: strategies
      for success.
AB  - As the role of the Acute Care Nurse Practitioner (ACNP) gains more recognition,
      ACNPs as well as prospective employers are eager to incorporate the position into
      a practice setting. Because the role is in its infancy, there has been limited
      experience from which to draw on to provide guidance in ACNP role implementation
      within a practice, either private or institutional. This article will provide
      foundational information and strategies on how to integrate the ACNP role into a
      practice setting. These strategies will be useful to not only the ACNP, but also
      nurse administrators, case managers, clinical nurse specialists, and nurse
      educators in acute and critical care who are responsible for seeking innovative
      ways to maintain seamless quality and cost-effective patient care.

PMID- 9248381
TI  - Merging a PICU and MICU: a debate.
AB  - One of the possible combinations when merging specialty units is combining a
      pediatric intensive care unit with an adult intensive care unit. The response
      related to the merging of these specialty units solicits very intense, diverse
      opinions. The authors address this controversial issue in a debate forum to
      present both sides of the issue.

PMID- 9248382
TI  - [Work absenteeism because of musculosceletal injuries].
AB  - The rate of occupational accidents with sick-leave has increased in the Valencian
      Community in the last few years. More specifically, a great part of the Temporary
      Occupational Leave (TOV) produced in the hospitalary field are a consequence of
      lesions related to the skeleton and muscle system. We consider that this
      absentism is theoretically avoidable and it is due to working conditions which
      can and must be modified. From this point of view, Health Education has a very
      important role in the prevention of these pathologies when it is focused to the
      health staff, and taught together with knowledge of pedagogy and a basic
      knowledge of ergonomy.

PMID- 9248383
TI  - [Repercussions of nursing activities on the intracranial pressure in patients
      with intracranial hypertension of traumatic or non-traumatic origin].
AB  - We study, in a prospective and randomized way, the influence existing between
      nursing maneuvers (suctioning, bathing and turning) and Intracranial Pressure
      (ICP) in patients diagnosed of Intracranial Hypertension Syndrome (ICHT). The
      study includes 22 patients admitted in Intensive Care at Hospital Universitario
      San Carlos (HUSC), during one year. All the patients had ICHT of traumatic or non
      traumatic origin. ICP was monitorized in every one through an intraventricular
      catheter and was over 20 Hg mm at admission or during 24 first hours of
      evolution. Doubt to the repercussion that the ICP values have on clinical
      evolutions we conclude that the nurse has to respond in an efficient, early and
      autonomous way in order to avoid uncontrolled elevation of ICP values during
      habitual management of patient.

PMID- 9248385
TI  - [Surviving in the intensive care unit].

PMID- 9248384
TI  - [Veno-venous hemofiltration with controlled ultrafiltration].
AB  - We haven't been using continuous veno-venous hemodiafiltration in our unit as an
      extrarenal depuration technique since 1991. With this work we want to provide our
      experience in what we call controlled ultrafiltration, technique which we have
      been using more frequently in the last two years and which consists on using the
      venous bomb of double head for ultrafiltration (UF) extraction, managing to
      obtain a more accurate control of it. The development of this technique has
      allowed us to obtain a higher control of the patient, reduce the risk of
      hypothermia and reduce the nursing burden. We show the procedure of priming,
      connection, disconnection and the necessary material, as well as the advantages
      and specific care we perform in our unit.

PMID- 9248386
TI  - [Techniques of extrarenal blood purification].

PMID- 9248387
TI  - [The Internet and nursing].

PMID- 9248388
TI  - [Food-drug interactions].

PMID- 9248389
TI  - The Frontier Nursing Service.

PMID- 9248390
TI  - The adventures of a Dean ... 1954.

PMID- 9248391
TI  - Individual rights and the human good in hospice.
AB  - Hospice care today faces economic, cultural, and social challenges that will
      force it to rethink its basic ethical mission and its basic values if it is to
      grow and prosper. Three different values can be said to inspire the hospice
      movement: palliation and the relief of suffering, enhancing individual control
      and autonomy at the end of life, and the value of healing or maintaining meaning
      and personal integrity in the dying process. An emphasis on palliation alone will
      not be sufficient to sustain a comprehensive hospice benefit in the future. An
      emphasis on patient autonomy alone is not in keeping with the history or spirit
      of the hospice movement, which in fact has had a vision of "good" dying. The
      notion of healing or making whole provides the richest and most adequate concept
      upon which to ground the social and ethical case for hospice care in the future.

PMID- 9248392
TI  - Issues of access in a diverse society.
AB  - Hospices are successful in addressing the needs of middle class, white, elderly
      persons with cancer who have family members able to care for them at home.
      However, there is a need to provide better access to care within diverse settings
      and for diverse populations. Ethnic minorities, marginalized persons and those
      without stable home environments or living in nontraditional ways are not well
      served by hospice at the present time. To improve access to hospice care,
      hospices need to address the distinctive profiles of their staffs and make them
      more inclusive and representative of the total community for their service area,
      create a broad range of programs of outreach, build bridges with other programs,
      develop expanded resources to manage the needs of patients and families, and
      train volunteers and staff to work in non-traditional home settings.

PMID- 9248393
TI  - Will assisted suicide kill hospice?
AB  - Hospice is often held out as an alternative to the need for assisted suicide. To
      date, those in the hospice movement have made any discussion of assistance in
      dying off-limits on the grounds that proper palliative care can address the
      concerns about pain that the terminally ill face. But, the movement toward
      assisted suicide raises questions about the future viability of the hospice
      movement in its current form. Many who see assistance in dying are concerned, not
      about pain, but about suffering and loss of dignity. Many are not terminally ill
      but terrified at the prospect of disability and loss of cognitive capacities.
      Unless hospice addresses these concerns it is not likely to survive in the face
      of pressures to legalize assisted suicide.

PMID- 9248394
TI  - Ethical issues in pain management.
AB  - The modern hospice movement has played a significant role in the development of
      palliative care. Effective palliation is of crucial importance in achieving
      quality of life and a dignified death for the terminally ill. While the inherent
      risk in palliative care, respiratory depression, remains an open medical
      question, an understanding of the ethical and moral principle of double effect
      demonstrates the prudential nature of palliative care and how it is an
      application of the ethical and moral norm, respect for patient autonomy.

PMID- 9248396
TI  - Legal requirements for confidentiality in hospice care.
AB  - In the absence of federal legislation or a federal constitutional right to
      medical privacy, state law governs hospice workers' legal obligations. States
      differ in the breadth and clarity of their law, how strongly they encourage
      preservation of confidentiality, what aspects of a medical encounter are
      confidential, and when a patient is deemed to have waived the right. All states,
      however, recognize a legal duty of confidentiality in certain circumstances, but
      also recognize exceptions to the duty. Understanding the law is necessary but not
      sufficient; hospice staff should be prepared to adjust procedures and physical
      surroundings to protect confidentiality.

PMID- 9248395
TI  - Focus on the nurse: ethical dilemmas with highly symptomatic patients dying at
      home.
AB  - Some serious issues face the inexperienced nurse who has the responsibility for
      either providing the care or directing the care of symptomatic patients dying at
      home. Inexperience in such care, and lack of competent medical support, can
      result in the nurse perceiving "ethical dilemmas" in practices which are, in
      reality, part of good and ethical palliative care.

PMID- 9248397
TI  - The role of the physician in hospice.
AB  - As the concept of hospice has evolved in the United States, it has become
      apparent that there is a significant need for increased physician participation
      in all aspects of the care of terminally ill patients provided by hospice
      programs. Four distinct physician roles have emerged: the attending physician,
      the consulting physician, the hospice medical director, and the hospice team
      physician. As the roles of the hospice medical director and team physician have
      become better defined, many physicians are finding that palliative medicine and
      full time hospice employment is a rewarding career option. The increased
      involvement of physicians in all aspects of hospice and palliative care will
      result in measurable improvement in the quality of patient care that hospice
      programs provide to terminally ill patients and families.

PMID- 9248398
TI  - The role of ethics committees in hospice programs.
AB  - Ethics committees are still relatively new to hospices, aside from those that are
      directly related to hospitals. This article takes a brief look at how one company
      formed and trained its ethics committees for several hospices providing care in
      the home setting. It delineates the composition of the committee, how the
      committee is trained, the functions of an operating committee, the various types
      of committees, and takes a look at the pitfalls and problems of such committees.

PMID- 9248399
TI  - Growth in caring and professional ethics in hospice.
AB  - There is a continual growing concern and impetus being placed on comprehensive
      care and treatment of the individual from birth to death. There is also strong
      evidence to lead one to believe that humanization of health care delivery must
      include attention to the development of health workers who are academically,
      emotionally, and psychologically prepared to deal with the dying patient and the
      family. Health professionals must learn to cope with anxieties arising from such
      experiences. This requires an adjustment period for the professional, a time for
      adaption and a working through of one's own feelings about death, dying and
      life's end. In other words, health professionals must come to grips with their
      own feelings about their own mortality, life's end and the in-between life
      processes. This paper identifies six stages that the health professionals must go
      through in learning to be comfortable in working with terminal illnesses and
      catastrophic diseases. This involves the Harper Schematic Comfortability Growth
      and Development Scale as a conceptual framework in learning to care for the
      terminally ill and dying.

PMID- 9248400
TI  - Hospice organizations' role in health care improvement.
AB  - Hospice organizations must understand and plan for their position in the proposed
      and ongoing changes in health care delivery in the United States. This paper
      proposes that hospice organizations shift their thinking about their role in the
      health care system. Hospices may view their work as processes which are impacted
      by many entities within the system of care; measure the outcomes of this work
      against the needs of patients, families and health care providers; and work to
      continually improve care. Aspects of this approach, and its implications for
      hospice organizations, are described. Using this new understanding, hospice
      organizations can both broaden their impact on care for larger numbers of dying
      patients, and position themselves to move forward within that system as the
      financial base and structure of health care change.

PMID- 9248401
TI  - Hospice and managed care.
AB  - Managed care is having a significant effect on the delivery of hospice care. A
      primary concern facing hospices is that reimbursement rates will likely either
      remain stable or fall. This suggests that competition between health care
      networks will lead to mergers and the closing of some hospices. A second
      challenge is the immense pressure to make decisions based exclusively on the
      cost/benefit ratio of hospice in a context where managed care organizations seek
      to increase market share and improve profits. To foster good hospice care within
      a managed care environment, service providers need to be defined, criteria for
      referral to hospice programs must be crafted, payments should be based on a per
      diem method, benefit packages should identify a comprehensive package of
      services, and agreements between hospices and managed care organizations should
      allow for routine review and amendments to their contracts.

PMID- 9248402
TI  - The future of hospice in a reformed American health care system: what are the
      real questions?
AB  - Many supporters of the hospice movement are concerned about changes being imposed
      on the movement by market-based reforms in the larger health care industry. But
      if they are to truly encourage the preservation of hospice's core goals and
      values in caring for vulnerable patients with terminal illnesses, they need to
      understand the realities of day-to-day hospice care under today's managed care
      system. The future of hospice in America will not be determined by its tax status
      or administrative structure, but by its functional integration into new systems
      of care, flexibility in response to emerging terminal care needs, commitment to
      standards and measurable quality outcomes and clearer articulation of the value
      an appropriately financed hospice movement can offer to patients at the end of
      their lives.

PMID- 9248404
TI  - The spiritual and psychological explanations for loss experience.
AB  - This paper examines the differences in the ability of patients to utilize
      supportive resources offered through hospice depending upon the individual's ego
      strength and spiritual resources. The author surveys psychological and spiritual
      theories for differences in how patients respond to terminal illness. The
      responses of three dying patients are analyzed relative to their ability to
      utilize emotional and spiritual support in the face of loss. Strategic approaches
      for hospice staff providing care are suggested.

PMID- 9248403
TI  - When the hospice patient is manipulative.
AB  - Oncology and hospice literature have addressed the problem of psychiatric
      complications, secondary to the stressors of diagnosis and treatment. This
      literature focuses particularly on depression and anxiety, which not only
      compound patients' suffering but also may interfere with optimal care. Little
      attention has been given, however, to the unique challenges of providing hospice
      care to patients with preexisting psychiatric conditions. As hospice care becomes
      increasingly mainstream in the health care system, we can expect to meet more
      patients with such conditions. In order to contribute to collegial dialogue that
      addresses this minority population in hospice services, a case study is presented
      in this article of the process of care for a hospice patient with a preexisting
      psychiatric condition. Interventions are suggested, using a theoretical matrix of
      hospice philosophy and principles of care for manipulative patients.

PMID- 9248405
TI  - Psychosocial and spiritual care in hospice: differences between nursing, social
      work, and clergy.
AB  - A chart review of the most recent home visits from nursing, social work, and
      clergy to 37 home hospice patients indicated that all but two psychosocial and
      spiritual issues examined were addressed by hospice staff on home visits.
      Spirituality and, secondly, death anxiety were the most frequently discussed
      variables. Clergy addressed more spiritual issues than the other two professions,
      and social work addressed more psychosocial issues than the other two
      professions. These findings underscore the important roles that clergy and social
      work play on the hospice team, and imply that hospice should make a renewed
      commitment to psychosocial and spiritual care.

PMID- 9248406
TI  - Palliative care: new challenges for advanced practice nursing.
AB  - The terminally ill are emerging as a specialized patient population that needs
      the expanded skills and knowledge of advanced practice nurses. These nurses can
      follow patients across a variety of settings in an integrated system of health
      care and over the continuum of living and dying. This paper addresses the concept
      of palliative care and the advantages of advanced practice nurse leadership in
      this area. Four major criteria for the establishment of a new advanced practice
      nursing area (American Nurses Association, 1995) serve as a framework. These
      criteria are: the area lies within the scope of nursing practice; a documented
      need exists; there is a body of knowledge upon which to base the practice; and
      the field of nursing would be diminished if the need were ignored. The author
      maintains that there is sufficient evidence for the creation of a new role:
      advanced practice nurse in palliative care.

PMID- 9248407
TI  - Elders' end-of-life decisions: implications for hospice care.
AB  - Elders' views on various end-of-life decision options were studied to determine
      each option's acceptability if they were faced with the need for such decisions.
      388 black and white elders aged 60 to 100 responded to 17 decision scenarios
      depicting situations with a low quality of life, rating acceptability of each of
      7 options for each scenario. Based on factor analysis of responses over
      scenarios, three scores were computed: maintaining life, ending life, and letting
      others decide. Profile types were identified and related to demographic
      background and personality variables. Implications for hospice care are drawn.

PMID- 9248408
TI  - Evidence-based medicine: what about evidence-based management?

PMID- 9248409
TI  - Management of change: an essential skill for nursing in the 1990s.
AB  - Change is nothing new and indeed has been our only constant, but change today is
      faster and more complex than it has ever been before (Manion 1994). Bushy (1992)
      agrees that the past decade has been a time for rapid global changes, with Muller
      (1992) citing the rapid increase in technology as the root cause. Muller (1992)
      believes that nurses need to develop a new mindset which is more in tune with the
      realities of the 1990s, acknowledging that we are and will be living in a
      constantly changing world, and Zukowski (1995) suggests that regardless of
      whether or not we accept change, we must learn to manage it. Although change
      creates uncertainty and discomfort, Poggenpoel (1992) emphasizes that it often
      leads to real innovation, providing abundant opportunities for creating a better
      way forward. This paper explores the subject of change management, looking first
      at the reasons behind the current climate of change in the healthcare system,
      then outlining change theory in relation to nursing, before discussing the role
      of the nurse as a change agent.

PMID- 9248410
TI  - The value of simulations in the management education of nurses: students'
      perceptions.
AB  - This paper examines the use of simulations in the education of student nurses as
      part of their preparation for management responsibility. A review of the
      literature indicates that there is little published work on this topic and that
      those evaluations that have been reported invariably occur at the end of the
      exercise, thus giving an incomplete picture of the simulation. The nature and
      format of the simulation, used with 128 students undertaking a pre
      registration/diploma in higher education course, is described. Results from
      student evaluations immediately following the exercise and after 13 weeks of
      clinical experience are presented. The findings indicate that this is a realistic
      and enjoyable way of learning which adequately prepares students for management
      experience in subsequent clinical allocations. Issues concerned with internal and
      external validity of simulations and areas for further research are explored.

PMID- 9248411
TI  - Out to tender--the nurses' role in awarding the contract for therapeutic
      bed/mattress hire.
AB  - AIM: A project group was established to award the contract for hire of
      therapeutic beds and mattresses for a large hospital Trust within the United
      Kingdom National Health Service (NHS). BACKGROUND: No structure existed for
      awarding or evaluating such a contract. Involving nurses in the process was
      intended to bring the decision-making nearer the patient. METHOD: The project
      group consisted of volunteers from a range of clinical nursing grades. They were
      highly motivated with an interest in pressure sore management. Expertise from NHS
      Supplies was also involved. RESULTS: The project group successfully awarded the
      contract, producing a robust operational tool through an objective process.
      Awareness was raised regarding control of expenditure and a commitment to
      education. Ongoing evaluation of the contract has also been the responsibility of
      this group. CONCLUSION: The project group achieved its aim of awarding a contract
      that best met the needs of the Trust and continues to monitor that contract. The
      systematic approach, comprehensive documentation and collaboration with NHS
      Supplies are felt to contribute to its success. Explicit criteria within the
      contract provides a clear framework for its monitoring and evaluation.

PMID- 9248412
TI  - Analysis of job-share as a process of change.
AB  - This paper describes the introduction of a district nursing job-share in a
      primary health care team. Exploring change theory and different strategies for
      organizational change, the implications for members of the team are considered.
      In addition, changes in the balance of power which resulted in conflict within
      the district nursing team are discussed.

PMID- 9248413
TI  - Evaluation of a health care assistant pilot programme.
AB  - Health Care Assistants (HCAs) were piloted in four wards of a large teaching
      hospital in Hong Kong. Evaluation of this pilot programme was based on patients'
      and nurses' satisfaction with HCAs, the HCAs' job satisfaction, and the retention
      rate of HCAs. Data were collected at 3 and 6-months following the introduction of
      HCAs to ascertain the level of satisfaction and the rate of HCA retention.
      Overall, the HCAs' work was seen as satisfactory and contributing to the work
      being carried out on each ward. Both nurses and patients were highly satisfied
      with HCA's, the mean total levels of satisfaction by nurses being 97 out of a
      possible range of 26-104 and for patients 53 out of a possible range of 14-56.
      While there was a high level of nurses' approval of introducing HCAs into the
      health care team there were significant differences (P < 0.05) with Nursing
      Officer, followed by Ward Managers being more in agreement than Registered
      Nurses. There were eight HCA activities seen by more than 70% of nurses to have
      been carried out frequently. The mean total job satisfaction of HCAs was 67 out
      of a possible 17-95. Although the 50% retention rate of HCAs was poor, there was
      overall satisfaction with the work of the HCAs.

PMID- 9248414
TI  - Case mix type as a predictor of nursing workload.
AB  - In the current health care service, the need to measure nursing workload has
      become the subject of major debate. Attempts have been made to relate workload
      and nurse staffing, however, despite there being systems for this there appears
      to be no single recognized formula. Case mix groups have been advocated as a
      useful tool for measuring nursing workload, particularly in Canada where work
      continues. Case mix groups work on the basis that patients who are clinically
      similar and use equivalent resources are grouped using procedure and diagnostic
      codes. The retrospective study examines the relationship between case mix,
      resource utilization and nursing effort to determine whether future workload
      could be predicted using these parameters. The sample included 798 patients and
      30 nurses over the period 1993-1994 with analysis of data from the Patient
      Administration System (PAS) and TEAMWORK, which purports to measure nurse
      workload. Results showed that there was little relationship between nursing
      workload and case mix grouping and recommendations are made for future research.

PMID- 9248415
TI  - Introducing change in nursing: the case of research.
AB  - This paper examines the issue of encouraging change in nursing and focuses on how
      to move from task-orientated to science-based practice. Therefore, it considers
      the current theory on the process of change and using two clinical vignettes (one
      from psychiatric and one from general nursing practice) illustrates how science
      based practice was introduced. From these vignettes it draws four conclusion: (1)
      small-scale cultural change is possible even within large bureaucracies; (2) the
      nature and identity of change agents is not always immediately obvious; (3) there
      is arguably no one singular best way of bringing about change and; (4) change
      activists need to have an understanding of several models of change. It then
      makes managerial, educational and structural recommendations based on these
      conclusions.

PMID- 9248417
TI  - Educators' responses to changes in the health care system.
AB  - A survey was conducted to identity programmatic/curricular changes made by New
      York state nursing schools in response to the changing health care environment
      and to identity the success of job placement for new graduates. Data were
      reported for 84 programs. Respondents indicated that innovative curriculum
      initiatives were employed, such as increasing community experiences and primary
      health care content. Opportunities for job placement were enhanced by a number of
      strategies, including resume writing and job interviewing workshops.

PMID- 9248418
TI  - Euthanasia and assisted suicide.
AB  - The topic of euthanasia/assisted suicide in the United States is emotionally
      charged. due to grassroots efforts, patient-initiated lawsuits, and attempts to
      punish those participating in physician-assisted suicide, the issue has been
      brought into the public eye and will not disappear. Nurses are challenged to
      consider this debate objectively in order to support public policy that leads to
      sensitive and appropriate patient care. This policy analysis examines how the
      issues of assisted suicide and euthanasia are being dealt with both nationally
      and internationally, and considers various policy options.

PMID- 9248419
TI  - Pressure ulcer prevention: review of literature.
AB  - Much has been written about the causes, prevention, and nursing management of
      pressure ulcers. A review of current literature on the subject reveals that, in
      spite of the enormity of information available, the problem continues to consume
      a large percentage of nursing time and energy. Studies of aggressive prevention
      and ongoing continuing education programs have demonstrated significant reduction
      of incidence and time of treatment, as well as dramatic cost savings. The Agency
      for Health Care Policy and Research (AHCPR) has recommended that all patients at
      risk for pressure ulcer development be placed on some form of pressure-reducing
      support surface. There is a wide variety of these products available, but a
      surprisingly limited quantity of published articles specifically compare the
      efficacy of one product to another.

PMID- 9248420
TI  - What can you do to assist float nurses who are assigned to your unit?

PMID- 9248421
TI  - Relational experiences of elderly women living alone in rural communities: a
      phenomenologic inquiry.
AB  - The purpose of this phenomenological study was to develop a beginning description
      of the relational experiences of elderly women living alone in rural communities.
      Relational theories provided the conceptual framework. Data were gathered through
      in-depth interviews of 8 elderly Caucasian women. Using Colaizzi's (1978)
      descriptive phenomenologic methodology, two central themes emerged from the
      written transcripts: connectedness and the need for control. Connections were to
      family, friends, the community, and God. The women in this study controlled their
      relational boundaries, balancing their need for connection with the desire for
      solitude and privacy. The women also exhibited strong independence and the desire
      to continue to live alone at home.

PMID- 9248422
TI  - Bibliography: nursing's professional image.

PMID- 9248423
TI  - [Malignant diseases in children--diagnosis and evaluation of the prognosis with
      tumor markers and special laboratory tests].

PMID- 9248424
TI  - [Gynecomasty in puberty].

PMID- 9248425
TI  - [Care planning for a 5 year old boy with quadriplegia].

PMID- 9248426
TI  - [Integrated education of future nurses and pediatric nurses in Switzerland].

PMID- 9248427
TI  - [Pediatric nursing in France. Educational structuring and the activities of a
      pediatric nurse in the departmental service for mother-infant protection].

PMID- 9248428
TI  - [Harmless changes in the anal and genital mucosa in the newborn].

PMID- 9248429
TI  - [Hospitals are liable for their nursing care].

PMID- 9248430
TI  - [Integration of parents of hospitalized children--a 3 year project of the action
      committee "hospitalized children"--federal association, promoted by the Federal
      Department for Family, Seniors, Women and Youth].

PMID- 9248432
TI  - Facing up to domestic violence.

PMID- 9248431
TI  - Reporting pressure sores.

PMID- 9248433
TI  - Antibiotic-resistant bacteria.

PMID- 9248434
TI  - Managing atopic eczema: the needs of children.
AB  - Atopic eczema is a common inflammatory condition of the skin. The disability and
      psychosocial impact of atopic eczema can be considerable. Existing dermatology
      clinics usually do not provide the time and the educational facilities essential
      for children with atopic eczema and their families.

PMID- 9248435
TI  - Reliability in reporting pressure sore incidence.
AB  - Encouraging the accurate reporting of pressure sores can be a difficult task. A
      telephone line for recording details on pressure damage may help to encourage
      reporting. An organisation-wide protocol for tackling pressure sores is needed.

PMID- 9248436
TI  - Domestic violence: the nursing response.
AB  - Nursing's response to victims of domestic violence may reflect that of society,
      with victim-blaming and reluctance to become involved being major problems.
      Nurses should improve their awareness in this area and call for training in
      dealing with such patients. Nurses should become involved in drawing up
      guidelines for practice in this area.

PMID- 9248437
TI  - Improving the nursing handover report.
AB  - The nursing handover report is a vital method of passing on essential information
      to nurses on the next shift. Nursing handover reports traditionally take place in
      private; they can become lengthy, irrelevant or unprofessional. Alternative
      methods of handover, such as bedside reporting, or tape-recording or writing
      reports, can help refine the process and make it more relevant to practice.

PMID- 9248439
TI  - Lymphoedema.

PMID- 9248438
TI  - Vancomycin-resistant enterococci: implications for infection control.
AB  - The incidence of vancomycin-resistant enterococci (VRE) infection is increasing.
      Immunosuppressed individuals are particularly vulnerable to infection with VRE.
      Strict attention to infection control measures is important in preventing the
      spread of multiresistant organisms.

PMID- 9248440
TI  - Mesothelioma.

PMID- 9248441
TI  - Immunocompromised patients and nutrition.
AB  - Most immunocompromised patients will have undergone bone marrow transplantation.
      These patients will require both nutritional support and some form of dietary
      restriction. Food restrictions used with patients undergoing BMT include a
      sterile diet, low-microbial diet or modified hospital diet. No empirical research
      exists on the relative benefits of each.

PMID- 9248443
TI  - Organising the nation's health.

PMID- 9248442
TI  - Patient moving and handling equipment.
AB  - Current regulations recommend that manual lifting should be avoided whenever
      possible. An ergonomic approach, based on full risk assessment and the use of
      moving and handling aids, will significantly reduce the risk of back strain and
      musculoskeletal injury. Ongoing training is required on manual handling
      techniques and equipment.

PMID- 9248444
TI  - Mercury versus disposable thermometers.

PMID- 9248446
TI  - What is advanced nursing?

PMID- 9248445
TI  - Confusion over pressure sore risk assessment scale.

PMID- 9248447
TI  - Cautious optimism.

PMID- 9248448
TI  - Accountability in urinary catheter management.
AB  - Catheterisation is traditionally considered an area of nursing expertise. Patient
      involvement in decision-making is important. Although considered autonomous,
      community nurses appear to encourage a large degree of medical involvement in
      decision-making related to catheterisation.

PMID- 9248449
TI  - Using models in learning disability nursing.
AB  - Nursing models and theory can be of particular benefit during periods of
      significant social and professional change. The use of nursing models in learning
      disability nursing needs to be shown to have positive outcomes in practice. A
      literature search found little proof of the efficacy of nursing models in
      learning disability nursing. More nursing research is essential in this area of
      practice.

PMID- 9248450
TI  - Managing atopic eczema: running a specialist clinic.
AB  - Specialist management of children with atopic eczema is directed towards
      education, treatment and reassurance of the child and family. A specialist clinic
      can tailor care to the individual needs of those attending. Specialist clinics
      should be constantly evaluated and developed to cope with the changing demands
      and needs of patients with atopic eczema.

PMID- 9248451
TI  - The place of humour in chronic or terminal illness.
AB  - The literature supports the use of humour as a therapeutic intervention. The
      ability to apply and comprehend humour is associated with coping skills and is
      particularly relevant to people with chronic or terminal illness. Whether or not
      the application of humour is therapeutic will depend on the nature of the
      communication and the relationship established between nurse and patient.

PMID- 9248452
TI  - Hormone replacement therapy.

PMID- 9248453
TI  - Prostate cancer.

PMID- 9248454
TI  - Advanced nursing roles: their worth in nursing.
AB  - Various factors have influenced the development of advanced nursing roles,
      including the quest for professional status and advances in medical science.
      Advanced nursing roles must be firmly based in a nursing philosophy and seek to
      improve patient care. Advanced nursing roles can benefit the individual nurse,
      the nursing profession, the consumer and the health-care organisation.

PMID- 9248455
TI  - Benefits and drawbacks of hospital-at-home schemes.
AB  - Hospital-at-home schemes provide intensive levels of care to actually ill people
      in their own homes. Such schemes may give care as an alternative to hospital
      admission or as an aid to early discharge. Benefits for the patient may include
      the reduced stress of being in familiar surroundings and the removal of
      travelling costs. Benefits to the health system may include shorter waiting-lists
      and a reduction in the length of patient hospitalisation.

PMID- 9248456
TI  - Stress.

PMID- 9248457
TI  - Pulse oximeters.
AB  - Pulse oximetry is a reliable and non-invasive method of measuring oxygen
      saturation. An understanding of the principles of operation is required to ensure
      its effective use. It is important to check the patient's history to ensure there
      are no factors which may cause monitoring problems.

PMID- 9248458
TI  - ["A new nurse will come to your house". Helping the patient at home means
      developing new approaches].
AB  - Health and Social theorists are lately promoting Home Health Care. As a not yet
      structured field, Home care could be a chance for nursing profession to check the
      costituent points in the light of the new demands. In spite of the difference
      between home and hospital setting, the new Italian university basic training
      doesn't cover community subjects. Analyzing also how the nursing metapardigm
      realizes itself in home and hospital, the author will demonstrate that home care
      could be the way to implement nurses theories and principles (self-care; person
      centered care; empowerment) more directly, freely, completely.

PMID- 9248459
TI  - [Introductory remarks to an empirical science of care].
AB  - The academic birth of the nursing science has created a disciplinary problem of
      the statute, epistemological bases of the relation between the sciences of nature
      and the sciences of man. The real subject of the nursing science is the care and
      its reason for being is in the ability of motivating with scientific and rational
      bases the choices of nursing care. Because of its characteristics the nursing
      science is tended towards the practice more than to a speculative knowledge, so
      the nursing science can be called "empiric science of care". It treats man in
      regard to quality, to relation, to the metaphoric interpretation of life and
      health more than to measurement. For its ability of investigate with
      methodological rigor, the nursing science is able to build a proper body of
      knowledges, crossing all the other disciplines involved in the study of man
      (cross-disciplinarity). Obviously, first of all, it's a question of
      pragmatic/assertive knowledge and only subordinately a nomothetic/predictive one.
      Evidently, nursing science and profession are not at once identifiable or
      overlying, we are going towards a new professional construction, which is
      changing the basic characteristics of the previous education, goes beyond it to
      reach another identity. Medicine is defined the "science of disease", differently
      from nursing which we can describe as a paradigmatic science of health.

PMID- 9248460
TI  - [What are the sexual discomforts of the institutionalized elderly and what do
      nurses know about the problem?].
AB  - The aims of this study were to identify the sexual problems of elderly people
      institutionalised in 2 nursing-homes and to find out how much the caregivers
      employed at these homes know about the sexuality-related problems affecting the
      elderly people they care for. Two questionnaires were issued: one to the
      residents of the home, the other to the caregivers. Results showed that the
      caregivers had very little awareness of sexuality in elderly people and of the
      particular problems and discomfort of those living in institutions. Discomfort
      was mainly due to loneliness, difficulty in communicating with caregivers about
      sentimental and sexual needs, finding new partners and lack of communication
      between the elderly person and his relatives regarding sexuality-related
      problems.

PMID- 9248461
TI  - [The teacher: who is he? What does he do?].

PMID- 9248462
TI  - [Analysis of the smoking habit in hospital health personnel].

PMID- 9248463
TI  - [Nursing interventions with patients who smoke, who are hospitalized with lung
      diseases].
AB  - The need of prevention and diagnosis is particularly perceived in relation to all
      problems concerning cancer. The cigarette smoke, one of the major preventable
      causes of disease and mortality, is often underestimated. The Author points out
      that nurses must assume a major role in the prevention field, as many people
      apply to them for information and advice. The results of an inquiry carried out
      in order to know whether and in which way nurses intervene to turn away their
      patients from smoke, are rather deceiving. A Guide for Action is then proposed
      with the aim of helping the nurse to care for this kind of patient with more
      knowledge and awareness.

PMID- 9248464
TI  - [Importance of the use of health protective measures for the prevention of
      hepatitis B, hepatitis C and HIV infections].

PMID- 9248465
TI  - [Fragmentation needs integration: the patient and his nursing care].
AB  - The Author analyses the psyco-physical conditions prevailing during illness and
      hospitalization: from the alterations taking place in the anti-stimulus barriers,
      to the damages in the oneself perception as a whole. Being at the same time a
      psychologist and a patient, the A focalizes the value she believes the most
      specific one of the nursing profession: to care for the body means to care for
      the person, while the awareness of the suffering conditions means to care for the
      fundamental needs of reassurance, psycho-physical integration and interpersonal
      communication.

PMID- 9248467
TI  - [Proposals on nursing legislation].

PMID- 9248466
TI  - [Project-Colombia 1996. Interview by Carmine Morelli].

PMID- 9248468
TI  - [Reforms in European health care. The Lubiana Charter on health care reform].

PMID- 9248469
TI  - [From Europe: nursing research. The association is representing the Italian
      nurses within the European Group of Research Nurses].

PMID- 9248470
TI  - Establishing philanthropic funds for advanced practice scholarships.
AB  - Because of decreased tuition assistance at some hospitals, experienced nurses
      interested in advanced roles may quit rather than stay and expand their roles.
      This author describes how a hospital based philanthropic community group has
      helped provide scholarships for nurses interested in advanced practice and how to
      set up a similar scholarship program that will retain these experienced and
      motivated nurses.

PMID- 9248471
TI  - Deciding to make the switch to ambulatory services.
AB  - With the health care environment changing so rapidly, this may be a time for
      nurse executives to consider moving from a traditional nurse executive position
      with inpatient focus to an ambulatory care or outpatient one. The nurse executive
      can evaluate her or his skills to determine if ambulatory administration is a
      good career move. In this article, the author, who has made the switch to
      ambulatory care, gives insightful advice to nurse executives who may be
      considering a similar move.

PMID- 9248472
TI  - [Children in pain: the need for better treatment].
AB  - Children in pain is an aspect of nursing and medicine that is almost ignored,
      evidenced by the almost complete lack of investigations in this field. Many
      factors impede the effective treatment of pediatric pain such as its difficulty
      of evaluation, incorrect suppositions and attitudes that discount their pain. It
      is imperative that medical professionals become cognizant of this shortcoming and
      begin to remedy it; our children are defenseless and are depending upon our care.
      The first thing we must do is believe the child all pain is real (if the patient
      says that it hurts, it hurts.) It is necessary that we apply the same care and
      precautions to the young as we do for teenagers and adults who are in situations
      that generate pain and stress. Postoperative care should include a special
      charting of pain that would become as routine as temperature and blood pressure.
      So that we might alleviate it, pediatric professionals need to learn evaluation
      techniques that would allow them to identify types of pain that manifest
      themselves in particular illnesses. A wide variety of pain-killing therapies are
      available to us to achieve this goal. Included in this arsenal are the opiates,
      which we can learn to approximately use when other analgesics are not effective.

PMID- 9248474
TI  - [Diet and insulin. Best results with an adjusted schedule].
AB  - Hospitalized diabetic patients with vascular disease, showing signs of infection
      and, perhaps, having had surgery, exhibit profound oscillations in their glucose
      levels. Better controls need to be followed to account for this variation between
      meals. To achieve this, the authors modified the meal schedules in a comparative
      study between two groups of patients that had been admitted to a cardiovascular
      surgical unit. The variable group consisted of 26 patients (group I) who were
      given a modified feeding schedule; the sample group that maintained the
      traditional schedule numbered 20 patients (Group II). All of these individuals
      have at least a 10 year history of diabetes and averaged 62 years of age. Glucose
      levels were measured every 6 hours for 20 consecutive days (normal glucose levels
      were considered 80-250 mg/dl). Results of the experiment were the following.
      Group I Breakfast 91%, Lunch 72%, Supper 77%, Snack 86%; Group II Breakfast 79%,
      Lunch 66%, Supper 69%, Bedtime 72%. As these findings indicate, a correct eating
      schedule for diabetics is a very important aspect in controlling proper blood
      glucose levels. Part of this work was presented at the VIII National Congress of
      Vascular Nursing, receiving first prize.

PMID- 9248476
TI  - [Report from the Spanish Society of Nurses, specialized in spinal cord lesions].

PMID- 9248473
TI  - [Internal craniocervical ligaments].

PMID- 9248475
TI  - [Application of diagnoses to a disabled population].
AB  - The application of a charting system designed in the C.S. "El Palo" has permitted
      the medical staff to detect nursing problems among its disabled population of
      health care patients. By using this system to categorize various diagnoses, it
      has been possible to study their incidence and help to prioritize their needs
      during continuing education sessions. The diagnostic profile of their disabled
      population include. Affected by physical immobility; Alteration of well being:
      pain; Difficulties with urinary elimination; Difficulties with intestinal
      elimination.

PMID- 9248477
TI  - [Adolescence and contraception].
AB  - The birthrate has decreased for all age groups except for adolescents. 4.51% of
      all pregnancies in Spain fall within the 15-19 year old age group. The prevention
      of adolescent pregnancy indicates the need for making family planning services
      more accessible to young people. The object of this study was a review of medical
      consultations performed in 1993 with adolescents at a family planning service.
      Among the most significant results are the following: the average age of menarche
      and coitus primaris was 11.8 years (+ or -2.2 years) and 16 years (+ or -1.7)
      respectively. The period between coitus primaris and the act of going to a family
      planning center was 9.1 months (+ or -2.3). 81.7% of those adolescents were
      advised to take oral contraceptives, 12.4% condoms, 1.96% the I.U.D. and 3.9%
      none. Among the most common side effects noted after taking oral contraceptives
      for 6 to 12 months were: psychic alterations (changes of mood, etc.), spotting,
      digestive upset, migraines and weight increase. The number of sexual partners
      before and after contraceptive use did not change significantly.

PMID- 9248478
TI  - [Satisfaction of ostomy patients].
AB  - INTRODUCTION: This study looks at the degree of satisfaction colostomy patients
      feel in regards to their perception of the health care that they receive, whether
      they think that their physicians care could improve and the level of the medical
      staffs professional experience. METHOD AND MATERIAL: The study was performed in
      the Area Hospitalaria de Valme (Sevilla). With a population of 350,000 possible
      patients of which 215 have an ostomy, 55 of these took part in the study. 215
      questionnaires were mailed to the ostomy patients with paid return mail enclosed.
      The survey was based on Lickerts attitude scale and had six items to respond to,
      using an evaluation of zero to five. This method is sufficiently valid and has
      been used in other studies such as project CORCH. RESULTS: First, averages were
      obtained for all items and variables. Second, a patient profile was obtained
      regarding sex and age. Third, a correlation of the three study variables was
      compared against variables of a global index of satisfaction. DISCUSSION: In
      contrast with the global index, the satisfaction of the patients in the study is
      very high (3.93 out of a possible 5). 45% of these patients perceive that the
      medical treatment that they receive could improve but that the professional
      experience of the medical staff is acceptable (62%).

PMID- 9248480
TI  - [What is known about pain in the newborn?].

PMID- 9248479
TI  - [Monitoring of blood glucose. Biosensors, a new monitoring system].
AB  - The education on the diabetic field, carried by nurses most of the time, is the
      most important therapeutic measure for the reduction of acute and chronic
      complications of the diabetic patient. One of the most important parts of the
      educational contribution consist on self-control; in order to reach said self
      control, it is necessary to practise the self analysis, being the best one the
      control of the capillary blood glucose. In this article, we are presenting a
      meter for glucose control of the latest generation; the meter has a biosensor
      technology and it extend its benefits when connected to a personal computer.

PMID- 9248481
TI  - [Understanding the role of place and gender in Brazilian women's health-illness
      processes].
AB  - The author deals with the social determination of the woman's health-illness
      process (through her social class and gender) linking it to the concept of social
      space, historically constructed, based on critical geography. The considerations
      made are illustrated with data collected in a study about the reproductive
      profile of woman who are assisted in public health units of the municipality of
      Sao Paulo.

PMID- 9248482
TI  - [Illness in adolescence: the health-illness profile of clients of basic health
      units in the city of Sao Paolo].
AB  - The aim of the present study is to verify the health-illness profile of
      adolescent users of a Basic Health Unit in the city of So Paulo (SP-Brazil).
      Empirical data were gathered through the retrospective analysis of individual
      reports, during the period of time in which a specific program for adolescents
      was developed, January 1988 to December 1991. The identified profile leads to a
      reflection concerning adolescents' life conditions and the correlated health
      illness process expressions, enabling the conclusion that the biological paradigm
      must be surpassed so that other dimensions of the adolescents' existence that
      interfere in their health-illness process can be expressed.

PMID- 9248483
TI  - [Organization of neonatal nursing in the region of Ribeirao Preto-SP. Brazil
      1992].
AB  - The present study analyses the organization of newborn care in different
      nurseries in the region of Ribeirao Preto as well as how nursing participates in
      this work. Through observation and interviews in 4 nurseries, we found that the
      work organization varies according to the hospital size and complexity. Action is
      centred on the child and in more complex cases, priority is given to the
      pathology and clinical care. We also observe enlarged actions, involving the
      binomial mother-child and the family. The quality of care is a result of a
      complex combination of human resources, material and installation. Bigger and
      more complex institutions present a diversity of personnel, more bureaucracy and
      hierarchy, information and technology system, routine procedures by written norms
      and more sophisticated equipment. The object of action is centred on the child,
      but there are practices in which the object is enlarged to the binomial mother
      child and the family.

PMID- 9248484
TI  - [Nursing care in neonatal units: measures for the prevention of cross
      infections].
AB  - The prevention of infection in nurseries requires measures related to nursing
      care in terms of the environment, equipment, personnel and the newborn. In view
      of the problems related to hospital infection, the objective of the present
      investigation was to determine the relationship between prescriptive measures for
      the Prevention of Infection and activities effectively carried out In a Neonatal
      Admission Unit. Participant observation and semistructured interviews were the
      strategies used for the investigation which allowed data collection. With this
      research we could see that prophylactic measures need to be taken together in a
      collection of activities based on adequate structure and facilities, performed by
      a cohesive professional team where everybody work towards the same goal. Measures
      taken isolated do not contribute to the effective accomplishment of
      prescriptions.

PMID- 9248485
TI  - [Organization of bone marrow transplantation and the nurses' performance].
AB  - This is a bibliographic study on bone marrow transplantation emphasizing nurses
      actions, reviewed from publishings of the last ten years. The organization of
      informations allowed authors to identify that for performing a transplant it
      would be necessary to have an adequate infrastructure, specialized human
      resources and operational resources for the assistance to be feasible. It was
      determined that nurses actions in this procedure are required in all stages of
      care, differently in each phase, and preferentially individualized and integral
      in a maximum ratio of one nurse for two patients.

PMID- 9248486
TI  - [The dynamics of dependency-autonomy in elderly patients after amputation of a
      lower limb].

PMID- 9248487
TI  - [Nursing and AIDS: knowledge and paradigm].
AB  - This study is a part of a research that comments the relation between Nursing
      Knowledge and AIDS. The actual period of time is treated like a period of
      transition between the modern science and one new paradigm. This is called post
      modern science. It brings the dynamics of AIDS in Brazil after the registration
      of 79,908 cases from 1980 to 1996. The main objective is to describe nursing
      knowledge that has based nursing care to seropositive and aidetic patients in an
      University-Hospital located in Rio de Janeiro, Brazil.

PMID- 9248488
TI  - [Reflexions on the functional method of nursing].
AB  - The main target of the present essay is to carry out a reflexion on the adoption
      of the functional method in nursing work, as well as on the criticism to this
      method. A secondary aim will be to show how the nursing team has been "using"
      this method in their daily work routine in the search for a more humanized
      nursing care.

PMID- 9248489
TI  - [Phenomenology: an alternative to nursing-research].
AB  - One of the methodological ways that can be used in research is phenomenology,
      that originated as a movement inside philosophy, being also applied in human
      sciences. In nursing, the application of phenomenology also represented a search
      for a methodological alternative in research. The proposal of this work is to
      contribute with some theoretical subsidies to the comprehension of
      phenomenological referentials. Initially this work presents some basic ideas of
      the phenomenology, as a philosophical branch, treating it as a methodological
      alternative in research, and approaching its utilization by nurses, as a
      methodology of investigation.

PMID- 9248490
TI  - [Profile of future nurses' aides in Campinas, SP, in 1995: reasons, expectations
      and problems related to their education].
AB  - The present study aims to characterize the profile of people studying in
      auxiliary nurse courses at the city of Campinas. The predominantly
      characteristics were: ages between 18 and 30 years old, majority female, single
      and catholic. The major part of the studied population does not work in nursing
      area, being the mainly motivation to begin the course the possibility of helping
      other people. Their difficulties were returning to school, conciliating the study
      schedule with other activities and paying the course.

PMID- 9248491
TI  - [Project of guidelines for the integration of nurses and managers in a district
      hospital].

PMID- 9248492
TI  - [Origin, development and acting out of violence].

PMID- 9248494
TI  - [On abortion and its legalization. A pastoral note at the Portuguese Episcopal
      Conference].

PMID- 9248493
TI  - [Fishbein's and Ajzen's model and work on the project].

PMID- 9248495
TI  - [The family and the smoking habits of adolescents].

PMID- 9248496
TI  - [A patient with erysipela, how to treat him?].

PMID- 9248497
TI  - [Bovine spongiform encephalopathy: Dormont's report].

PMID- 9248498
TI  - [Impotence: at last there is hope].

PMID- 9248500
TI  - Black times: temporal determinants of transport safety.
AB  - This paper is concerned with whether transport accident risk tends to peak at
      particular times, in relation to both time of day and time on task, and with the
      underlying causes of such peaks. Macro-analyses confirmed the presence of a clear
      circadian (ca 24 hour) rhythm in road accident risk with a major peak at ca 03:00
      but suggested that this rhythm could not be entirely accounted for in terms of
      drivers falling asleep at the wheel. Sleep propensity clearly shows a pronounced
      circadian rhythm and performance efficiency in wakeful subjects shows a similar
      trend implying that the 03:00 road accident peak may simply reflect lowered
      performance capabilities. However, there are 'residual' peaks in accidents at
      certain times of day that are difficult to account for in terms of circadian
      rhythmicity. It is suggested that these may reflect a time on task effect which
      shows a pronounced, but transient, 2-4 hour peak in risk. Only when individuals
      had been on duty for 12 hours or more did the risk exceed that found during the 2
      4 hour peak. While an explanation for this transient peak is offered, the
      underlying reason for it is, as yet, uncertain and clearly warrants investigation
      in view of its practical implications. It is concluded that there are 'black
      times' when accidents are far more likely and that there is a strong need to
      investigate possible countermeasures.

PMID- 9248501
TI  - Time of day variations in driving performance.
AB  - Numerous factors may contribute to the 24-hour pattern of automobile accidents.
      One factor may be a time of day variation in driving ability. In the present
      study, 11 male subjects operated a driving simulator for 30 minutes at six times
      of day. Subjects were instructed to maintain a stable position in the left-hand
      lane and to drive at a constant speed of 80 km/hour. In addition subjects
      performed a secondary reaction time task. Subjective mood was measured at the
      beginning and end of each session. Driving performance was measured in terms of
      the mean and standard deviation of lateral position and speed. The mean and
      standard deviation of speed varied significantly across the day for both curved
      and straight segments. Reaction time was also affected by time of day.
      Performance was more impaired at 0600 and 0200 hours, with improvements in
      driving performance between 1000 and 2200 hours and an early afternoon dip. These
      results suggest that driving performance is subject to diurnal variations. Of
      particular importance is the result that impairments in driving performance in
      the early afternoon are of a similar magnitude to those occurring in the late
      evening and early morning.

PMID- 9248499
TI  - Fatigue, mindset and ecology in the hazard dominant environment.
AB  - Ratings made by 47 experienced drivers to 18 items of a Fatigue Advisory are
      highly consistent. Every item is rated 'very' or 'extremely important' to the
      safety of inexperienced drivers. In contrast, 'adequacy of knowledge' about
      fatigue is rated consistently lower. This inconsistency may reflect a culturally
      based confusion about fatigue. Education and public awareness campaigns need to
      emphasize that 'immoderate indulgence of driving' is as dangerous to safety as
      'immoderate indulgence of alcohol'. A basic challenge is to improve understanding
      of the manner in which the experience of fatigue emerges during driving. Study of
      perceptual/cognitive manifestations aided by operational definition of fatigue as
      a 'declarative state' renders driving fatigue a definite observable subjective
      condition arising from continuous operation of a vehicle. Specific cognitive
      symptoms of fatigue such as boredom, tiredness, inattention, etc. emerging with
      driving fatigue, are circumscribed within the activity of driving itself and also
      reflect the particular conditions in which driving fatigue occurs. This approach
      reveals ecological dimensions to the problem. The specific experiences of driving
      fatigue are seen to emerge as a function of the driver environment relationship
      in a particular driving environment. It is suggested that the concept of the
      'hazard dominant environment' and the compensating landscape perceptions of
      'prospect' and 'refuge' proposed by Appleton [(1995) The Experience of Landscape.
      Wiley, London] in concert with the concept of environmental 'affordances'
      provided by Gibson [(1979) An Ecological Approach to Visual Perception. Houghton
      Mifflin, Boston] open promising possibilities for improving environmental
      education about driving fatigue.

PMID- 9248502
TI  - Aircrew fatigue in long-haul operations.
AB  - The studies were conducted on the transmeridian routes Dusseldorf (DUS)-Atlanta
      (ATL) and Hamburg (HAM)-Los Angeles (LAX), and on the north-south route Frankfurt
      (FRA)-Mahe (SEZ). Scheduled flight duration was between 8:50 hours (ATL-DUS) and
      11:50 hours (HAM-LAX). In total, 25 rotations (50 flights) have been investigated
      by pre-, in- and post-flight data collection of sleep, taskload, fatigue and
      stress by electroencephalogram and electrocardiogram measurements and subjective
      ratings. Inflight ratings of taskload showed low perceived exertion during the
      Atlantic flights, and were moderate during the north-south transitions. Fatigue
      ratings increased with progressing flight duration. Towards the end of long U.S.
      westcoast flights performed at day-time, and in all night flights, fatigue was
      elevated compared to the 'baseline' ratings collected during the day-time DUS-ATL
      flights. Fatigue was rated as being 'critical' by several pilots, particularly
      during the return flight SEZ-FRA when fatigue was severely pronounced. From the
      findings it is concluded that duty schedules, as performed on the route HAM-LAX
      (because of long duty hours), and particularly on the route FRA-SEZ (because of
      consecutive night work), may place excessive demands on mental and physiological
      capacity. With respect to legal aspects, the results are significant and should
      promote further deliberations for advanced schemes of flight duty time
      limitations and rest requirements.

PMID- 9248503
TI  - Sleepiness and driving: the experience of U.K. car drivers.
AB  - This paper presents the results of a postal questionnaire survey of just over
      4600 male drivers aimed at exploring the relationship between accidents and
      daytime sleepiness. Drivers in this survey provided details of the accidents they
      had experienced in the last 3 years, and identified those factors they thought
      had contributed to their accidents. In addition to the normal demographic and
      exposure variables, drivers completed the Epworth scale measuring daytime
      sleepiness. Drivers also reported whether they had felt close to falling asleep
      whilst driving during the past 12 months and whether the car they drove most was
      privately or company owned. The analysis of this data has identified the
      characteristics of tiredness-related accidents. The probability of feeling close
      to falling asleep at the wheel has been related to demographic variables and the
      Epworth score using a logistic model. Drivers reported that ca 7% of accident
      involvements were associated with tiredness (ca 9-10% of accidents). The accident
      liability of the drivers has been evaluated using a multivariate statistical
      model; for some drivers, accident liability is shown to be sensitive to daytime
      sleepiness.

PMID- 9248504
TI  - Driver fatigue in the city.
AB  - The current survey investigates the features of driver fatigue incidents
      (accidents, near accidents and unintentional drifting-out-of-lane events) which
      occurred in cities. The results show similar patterns to previous surveys, with
      incident trips tending to be short, and prior sleep loss and late night driving
      featuring as factors. Work trips feature very strongly among city fatigue
      incident trips and work is also a common reason for sleep loss before a fatigue
      incident. Consistent with the high representation of work trips, there are peaks
      in incident occurrence at commuter travel times. Shiftworkers are prominent
      amongst fatigue incident-involved drivers. Social trips also feature amongst
      fatigue incident trips but are likely to be more difficult to address with
      countermeasures.

PMID- 9248505
TI  - Hours of work, and perceptions of fatigue among truck drivers.
AB  - Drivers and companies operating in the heavy road transport industry were
      surveyed about drivers' hours of work and perceptions of the causes and magnitude
      of fatigue as an industry problem. These drivers were operating in a state which,
      at the time of the survey, did not restrict driving hours for heavy haulage
      drivers. On the day of the interview, estimates based on retrospective and
      prospective reports, suggest that in a 24 hour period about 38% of drivers exceed
      14 hours of driving, and 51% exceed 14 hours of driving plus other non-driving
      work. About 12% of drivers reported less than 4 hours of sleep on one or more
      working days in the week preceding the interview. These drivers are likely to be
      operating their vehicles while having a significant sleep debt. About 20% of
      drivers reported less than 6 hours sleep before starting their current journey,
      but nearly 40% of dangerous events that occurred on the journey were reported by
      these drivers (p < 0.05). Many drivers and company representatives reported
      fatigue to be a problem for other drivers, but considered themselves or their
      companies' drivers to be relatively unaffected by fatigue. There were differences
      between drivers' and companies' perceptions about causes of fatigue, and
      strategies that should be used to manage it. The results obtained from these
      drivers in an unregulated state were compared with earlier findings from drivers
      in states where driving hours restrictions are in place.

PMID- 9248506
TI  - Development of fatigue symptoms during simulated driving.
AB  - Why do people sometimes allow themselves to be overcome by fatigue? Ancient human
      survival may have depended on ignoring fatigue. Its modern occurrence in the
      absence of strain may further render us insensitive to its warning value. To test
      whether deliberate monitoring of certain symptoms may help drivers and other
      workers realize when they need to rest to avoid hazard, the development of
      fatigue while driving a simulator was objectively measured in terms of how many
      persons quit driving as a function of time. Some subjects asked to stop after 90
      minutes; others lasted 240 minutes. Grouping data from an adapted Pearson [(1957)
      Journal of Applied Psychology, 44, 186-191] fatigue checklist revealed a curious
      phenomenon. No matter how long subjects drove before wanting to quit, they still
      developed much the same subjective level of fatigue at the end. This suggests
      that people do not differ greatly in how much fatigue they can tolerate but
      rather how quickly they reach a certain critical level of fatigue. Averaging
      fatigue scores backwards from the time subjects quit produced a function similar
      to the quitting function. Similar treatment of the other data revealed certain
      clusters of symptoms whose development also paralleled the development of
      fatigue.

PMID- 9248507
TI  - Motor vehicle accidents, fatigue and optimism bias in taxi drivers.
AB  - Fatigue-related variables and their relationship with accident involvement were
      examined in a group of 42 Sydney metropolitan taxi drivers across a 2-year
      period. Advantages associated with the study of this group of road users include
      their important role in public transport, long hours spent on the road, job
      related controls of exposure through shift patterns and the ability to verify
      accidents with company insurance records. Number and length of breaks, employment
      type, falling asleep at the wheel and a variety of other job-related and
      attitudinal variables were surveyed. Results provide basic data on fatigue
      related aspects of the job of taxi driving. Driver time-on-the-road is often
      considerable: 67% of those surveyed drove at least 50 hours per week, yet time
      off in long shifts (up to 12 hours) was often short (as low as 3 minutes, with an
      average of 37 minutes). Self report of accidents proved reliable against
      insurance company records. A significant negative correlation between total
      average break time and accident rate was observed. Optimism bias was present for
      a variety of driving-related questions, including the ability to drive safely
      while fatigued.

PMID- 9248509
TI  - Adaptation to the driver as part of a driver monitoring and warning system.
AB  - A driver monitoring and warning system called DAISY (Driver AssIsting SYstem) is
      presented, which adapts its warning messages to warning thresholds acceptable to
      the driver. This is achieved by the use of a model of the individual driving
      behaviour of the driver actually driving. Artificial neural networks based on the
      ART architectures were used for on-line learning to realize this model. Besides a
      brief survey of the main features of DAISY this paper emphasizes the modelling of
      the driving behaviour with ART networks. The way the ART networks are adapted to
      the problem is described. This includes the realization of a hierarchical ART
      structure and of a situation specific weighting of the components of the feature
      vector. The network parameters were adjusted through genetic algorithm
      optimization.

PMID- 9248508
TI  - Fatigue, workload and adaptive driver systems.
AB  - This paper is directed to the further understanding of the problems of fatigue
      and workload and their role in diminishing driving capability. We present a
      specific strategy designed to defend against the adverse effects of fatigue and
      workload extremes through the use of adaptive driver systems. To begin, the work
      presents a brief critique of Muscio's constraints on developing a test of
      fatigue. In criticizing these constraints, we point to the commonalities between
      all energetic reflections of human performance and use advances in stress theory
      to explain the problems of and resolution to the question of fatigue. We link
      fatigue and chronic workload and use this coadunation as a basis for the
      operation of adaptive driver systems which are specifically designed to combat
      driving impairment. A specific program is then explained in detail and
      illustrations are given as to how an extension of previous efforts can address
      the problem of the drowsy and chronically fatigued driver. Future recommendations
      are articulated.

PMID- 9248510
TI  - Implications of task-induced fatigue effects for in-vehicle countermeasures to
      driver fatigue.
AB  - Two driving simulator studies are reported which investigate the variation of
      fatigue effects with task demands and provide recommendations for system design
      to counteract driver fatigue. Two opposing explanations of the interactive
      effects of task demands and fatigue were examined. One explanation is that
      fatigue drains attentional resources, so that detrimental effects of fatigue on
      performance are accentuated when task demands increase. The alternative
      explanation is that fatigue disrupts matching of effort to task demands, such
      that the fatigued driver fails to regulate effort effectively when the task
      appears easy. In both studies, drivers performed both a fatiguing drive, in the
      first part of which they were required to perform a secondary detection task, and
      a control drive with no additional secondary task. In the last part of both
      drives, drivers were required to detect movement in pedestrian stimuli presented
      on both sides of the road. Vehicle control and steering movements were logged
      throughout both drives. The results are consistent with dynamic models of stress
      and sustained performance which suggest that fatigue may impair adaptation to
      conditions of underload, but are inconsistent with the attentional resource
      explanation. These task-specific fatigue effects have important implications for
      in-vehicle countermeasures to driver fatigue. Current approaches to the
      implementation of such devices fail to reflect the task-specific nature of
      fatigue effects. Fatigue-monitoring devices may only be valid in certain driving
      environments or contexts. Hence, it may be necessary to integrate performance
      based feedback monitoring information with route and traffic density information
      from navigation systems.

PMID- 9248511
TI  - Prospects for technological countermeasures against driver fatigue.
AB  - There are three reasons for giving serious consideration to technological
      countermeasures against driver fatigue: 1, fatigue is a persistent occupational
      hazard for professional drivers; 2, some professional drivers are under
      considerable pressure to reach their scheduled destination, in spite of feeling
      drowsy; 3, fatigue adversely affects an individual's ability to assess their own
      fitness to continue driving. However, there are two reasons for exercising
      caution in implementing technological countermeasures: 1, their reliability under
      real traffic conditions is largely unproven; 2, they could be used by
      unscrupulous drivers to support the continuation of journeys that should have
      been terminated because of human impairment. This paper draws on the findings of
      research into the origins, symptoms and development of human fatigue, and on
      recent research into driver-support systems, to assess the prospects for
      implementations of technological countermeasures against driver fatigue in the
      foreseeable future.

PMID- 9248512
TI  - The influence of sustained attention on railway accidents.
AB  - Train accidents and near accidents occurring over a 3-year period were examined
      within an Australian public rail authority. Retrospective analysis of 112
      incidents according to Reason's (1992) Generic Error Modelling System (Reason,
      1992, Human Error. Cambridge University Press, Cambridge), revealed a propensity
      of skill based errors across the more common types of rail mishaps. In agreement
      with previous rail research, sustained attention was the most salient
      contributing human factor across all incident types, particularly inattentiveness
      to railway signals. The unfavourable nature of the working environment and the
      repetitive nature of the train driving task are discussed in light of reducing
      attentional deficits. In addition, a Railway Safety Checklist was developed to
      identify train drivers perception of safety. One hundred and ninety train drivers
      indicated that staff attitude in the form of low morale was a serious problem in
      the safe conduct of their job. The results of this study imply that useful
      strategies for improving driver vigilance should be directed at improving the
      safety culture of the operating environment.

PMID- 9248513
TI  - Balancing work and rest to combat driver fatigue: an investigation of two-up
      driving in Australia.
AB  - This study is the fourth in a series examining driver fatigue in the Australian
      long distance road transport industry. Thirty-seven long haul truck drivers were
      measured on a routine 4500 km round trip. Two types of driving operations were
      compared, single driving, involving a solo driver, and two-up driving, where a
      pair of drivers operate a truck continuously and alternate between work and rest.
      Two-up drivers reported higher levels of fatigue than single drivers overall and
      tended to show poorer levels of performance. However, this result appeared to
      reflect differential fatigue at the start of the trip. Both two-up and single
      drivers showed marked increases in fatigue across the first half of the trip,
      followed by a substantial recovery of alertness and performance provided that
      drivers had stationary overnight rest at mid trip or had shorter trips. Fatigue
      continued to increase on the second half of the trip for drivers who did longer
      trips without the benefit of a substantial night rest or who did not have access
      to on-board rest, that is single drivers. The use of overnight rest, in
      combination with two-up driving, appeared to be the most successful strategy for
      managing fatigue across the trip.

PMID- 9248514
TI  - Human sleep/wake regulation.
AB  - The present paper gives a short overview on what is known about human sleep/wake
      regulation and focuses on two main component, the homeostatic component and the
      circadian. The homeostatic components increases sleep need exponentially as a
      function of prior wakefulness whereas the circadian component is a consequence of
      the 24-hour physiological rhythm facilitating sleep during the night and
      counteracting sleep during the day. Normally, these components interact, in an
      additive way. This interaction has been described in mathematical models that can
      be used to predict sleep duration, depth of sleep and the level of alertness
      given the knowledge of circadian phase and prior time awake.

PMID- 9248515
TI  - The perturbations of various CNS functions by anaesthetic drugs.

PMID- 9248516
TI  - Cerebral dysfunction after anaesthesia.

PMID- 9248517
TI  - Strategies for labor pain relief--past, present and future.

PMID- 9248518
TI  - Obstetric emergencies.

PMID- 9248519
TI  - Prevention of aspiration pneumonitis in the obstetric patient.

PMID- 9248521
TI  - Anaesthetic management of the pre-eclamptic woman.

PMID- 9248520
TI  - Anaesthetic lessons to be learnt from confidential inquiries into maternal death.

PMID- 9248522
TI  - Pulmonary artery catheterisation.

PMID- 9248524
TI  - Pulmonary artery catheterisation. Con.

PMID- 9248523
TI  - The use of pulmonary artery catheter improves quality of care.

PMID- 9248526
TI  - Pathophysiology of aortic cross-clamping.

PMID- 9248525
TI  - Aspects on the cerebral perfusion pressure during therapy of a traumatic head
      injury.
AB  - An actively raised cerebral perfusion pressure by vasopressors is nowadays often
      advocated during therapy of a post traumatic brain oedema to improve oxygenation
      of the brain. In this paper we argue that the arterial pressure not uncritically
      can be raised as the subsequent increase in hydrostatic capillary pressure may
      favour transcapillary filtration if the blood-brain barrier is opened for
      solutes. Further, the use of vasoconstrictor drugs to increase the perfusion
      pressure may in fact impair oxygenation to the penumbra zones around brain
      contusions but also to other tissues of the body, like the intestinal mucosa and
      the kidney. An alternative therapeutical concept which both ensures an adequate
      oxygenation of the brain and controls the intracranial pressure (ICP) is given.
      In short, it implies active antistress and sedative treatment, adequate fluid
      therapy with blood and colloids to normal haemoglobine and albumin values,
      artificial ventilation to normal PaCO2 and PaO2, and this in combination with
      antihypertensive and catecholamine reducing treatment with alpha 2-agonist and
      beta 1-antagonist.

PMID- 9248527
TI  - Renal protection during surgical stress.

PMID- 9248528
TI  - Fiberoptic assisted airway management.

PMID- 9248529
TI  - Therapeutic approach in early and late ARDS.

PMID- 9248530
TI  - General or regional anaesthesia.

PMID- 9248531
TI  - General or regional anaesthesia--pro general.

PMID- 9248532
TI  - General or regional anaesthesia--pro regional.

PMID- 9248533
TI  - Transoesophageal echocardiography.

PMID- 9248534
TI  - Transesophageal echocardiography.

PMID- 9248535
TI  - Transesophageal echocardiography.

PMID- 9248536
TI  - Difficult intubation.

PMID- 9248537
TI  - Percutaneous tracheostomy.

PMID- 9248538
TI  - Bronchoscopy in airway management.

PMID- 9248539
TI  - Prehospital care in France, current status and international controversies.

PMID- 9248540
TI  - Prehospital care, importance of early intervention on outcome.
AB  - The improvement of rescue systems and on-scene therapy has lead to a significant
      reduction of early posttraumatic death. It was the goal of this study to
      critically analyse the value of prehospital care in respect to early but also to
      delayed complications (single = SOF or multiple organ failure = MOF) In a
      retrospective analysis 1223 polytraumatized patients treated during 1984 and
      1994, with an injury severity of more than 20 points according to the Injury
      Severity Score = ISS, on-scene therapy ("field stabilization") was evaluated. We
      could show that a sufficient preclinical airway management has major influence on
      late prognosis (MOF). We therefore definitely recommend early intubation at the
      scene in these patients. The intravenous access at the emergency place is always
      necessary independent whether the patient is in hemorrhagic shock or not. Loss of
      time can increase shock mechanisms making intravenous access even more difficult.
      If there is already a peripheral vasoconstriction and the localisation of an
      peripheral vein renders more difficult, one possibility is a venae section to get
      safe access. Concerning the amount of preclinical infusion controverse opinions
      exist. Our evaluation could not give an satisfactory statement because of a
      differing high incidence of mass bleeding in the groups with low (< 1000 ml) and
      high (> 2000 ml) preclinical infusion. The improvement of rescue systems and on
      scene therapy has lead to a significant reduction of early posttraumatic death.
      Especially in those injuries, that are directly associated with the development
      of early death, i.e. intracranial bleeding, massive hemorrhage from thoracic and
      intraabdominal lesions these regimens on scene improved survival significantly
      (Fig 1) (Trunkey 1983). Nevertheless it is still discussed whether a longer
      rescue time is then justified to intensify on scene therapy. Recent publications
      demonstrate for instance that infusion therapy beginning on scene is not always
      necessary and sometimes especially in severe hemorrhagic shock can even aggrevate
      bleeding (Bickell 1989, Bickell 1991, Bickell 1993, Crawford 1991, Gross 1988,
      Stern 1993). On the other hand the value of on scene intubation and ventilation
      and chest tubing in these patients is critically discussed (Mattox 1989). Most of
      these studies however have their origin in the USA and are related exclusively to
      penetrating trauma (knife and gunshot wounds), which is completely different from
      underlying pathomechanisms (pure hemorrhagic shock). Only one reports of the same
      experience with blunt trauma (Barone 1986). Thus for severe blunt trauma the
      question is still open: "field stabilization" or "load and go" (Krausz 1992). A
      decision that always has to be related to the definite rescue time (Smith 1985).
      It was the goal of this study to critically analyse the value of prehospital care
      in respect to early but also to delayed complications (single = SOF or multiple
      organ failure = MOF).

PMID- 9248541
TI  - Efficacy of hypertonic saline dextran (HSD) in patients with traumatic
      hypotension: meta-analysis of individual patient data.

PMID- 9248542
TI  - Prehospital management of patients with acute coronary syndromes.

PMID- 9248543
TI  - Telemedicine--future implications.

PMID- 9248544
TI  - The living and dying cell.

PMID- 9248545
TI  - Tissue oxygenation--circulatory aspects.

PMID- 9248546
TI  - Cytopathic hypoxia in sepsis.
AB  - Diminished availability of oxygen at the cellular level might account for organ
      dysfunction in sepsis. Although the classical forms of tissue hypoxia due to
      hypoxemia, anemia, or inadequate perfusion all might be important under some
      conditions, it seems increasingly likely that a fourth mechanism, namely
      cytopathic hypoxia, might play a role as well. The term cytopathic hypoxia is
      used to denote diminished production of adenosine triphosphate (ATP) despite
      normal (or even supranormal) PO2 values in the vicinity of mitochondria within
      cells. At least in theory, cytopathic hypoxia could be a consequence of several
      different (but mutually compatible) pathogenic mechanisms, including diminished
      delivery of a key substrate (e.g., pyruvate) into the mitochondrial tricarboxylic
      acid (TCA) cycle, inhibition of key mitochondrial enzymes involved in either the
      TCA cycle or the electron transport chain, activation of the enzyme, poly-(ADP)
      ribosylpolymerase (PARP), or collapse of the protonic gradient across the inner
      mitochondrial membrane leading to uncoupling of oxidation (of NADH and FADH) from
      phosphorylation of ADP to form ATP. Tantalizing, but limited, data support the
      view that cytopathic hypoxia occurs in both animals and patients with sepsis or
      endotoxemia.

PMID- 9248547
TI  - Therapeutic aspects of oxygen delivery.

PMID- 9248548
TI  - Therapeutic aspects of oxygen utilisation.

PMID- 9248549
TI  - Should a neuromuscular block be reversed?

PMID- 9248550
TI  - Reversal of neuromuscular block: the case FOR reversal.

PMID- 9248551
TI  - Reversal of nondepolarizing block: only when necessary.

PMID- 9248552
TI  - Patients with congenital heart malformations for noncardiac surgery.
AB  - Most patients with CHD can be safely anesthetized with regular techniques.
      Preoperative consultation with appropriate specialists and a well planned
      anesthetic management is important.

PMID- 9248553
TI  - How to maintain uteroplacental perfusion during obstetric anaesthesia.

PMID- 9248554
TI  - Neuromuscular function in the I.C.U.

PMID- 9248555
TI  - Mapping brain function with magnetic resonance imaging.

PMID- 9248557
TI  - Power spectral analysis of arterial pressure signals: physiologic principles and
      clinical applications.

PMID- 9248558
TI  - On a novel MRI technique (OMRI) for the determination of tissue parameters.
AB  - In clinical diagnostic medicine the assessment of key physiological tissue
      parameters is important. OMRI is a novel ultra-low field MR-technology taking
      advantage of the Overhauser effect in order to enhance the signal. However, the
      technology further enables the visualization of tissue oxygen due to its
      interaction with an administrated CM. Experimental results from rats show
      morphological images of high resolution and further the alternation of tissue
      oxygen as a function of various external physiological conditions. It is believed
      that the novel technique enables and expands bed-side diagnosis.

PMID- 9248556
TI  - Transgenic analysis of central nervous system development and regeneration.
AB  - The transgenic technique allows specific genetic alterations to be made in all
      cells of an animal and this has greatly improved our understanding of how the
      embryonic and adult central nervous system (CNS) develop. The CNS originates from
      the neuroectoderm in the neural plate on the dorsal side of the embryo and after
      closure of the neural tube the cells of the neuroepithelium, i.e. the CNS stem
      cells, transiently proliferate to generate neurons and glial cells. Here we
      review our attempts to gain insights into the control of CNS development. We have
      identified a gene, nestin, which is predominantly expressed in embryonic and
      adult CNS stem cells. In addition to its normal expression in the CNS stem cells,
      nestin is reexpressed in CNS tumors and in the adult spinal cord and brain after
      CNS injury. By using the lacZ reporter gene assay in transgenic mice, we have
      identified regulatory regions (enhancer) in the nestin gene required for
      expression in embryonic CNS stem cells and in the adult spinal cord after injury.
      In a second project, we have cloned and characterized the Notch gene family (the
      Notch 1, 2 and 3 genes) in mouse and man. These genes encode trans-membrane
      receptors, which appear to be key regulatory molecules for proliferation and
      differentiation both in the developing CNS and in other tissues. Expression of an
      activated form of the Notch 3 receptor from the nestin promoter in transgenic
      mice leads to a lethal, exencephaly-like phenotype in the embryo, probably as a
      result of excess proliferation of the CNS stem cells. The recent finding that the
      Notch 3 gene is the genetic cause for familial stroke is discussed in the context
      of current models for Notch function.

PMID- 9248559
TI  - Microdialysis--a new technique for monitoring local tissue events in the clinic.

PMID- 9248560
TI  - Update on spinal cord pharmacology in pain.

PMID- 9248561
TI  - Mechanisms of central pain.

PMID- 9248562
TI  - Memory for pain.

PMID- 9248563
TI  - Chronic pain and the sympathetic nervous system.

PMID- 9248565
TI  - Thermodilution in medicine.

PMID- 9248564
TI  - Adenosine for pain control.
AB  - The antinociceptive actions of adenosine and adenosine analogs in animal models
      has been known for more than 10 years. The recent development with regard to the
      pain modulatory effects of adenosine, primarily in clinical studies, has
      generated a renewed interest in this principle for pain control. This review
      summarizes the current knowledge in adenosine mediated pain modulation in acute
      and chronic conditions, with focus on studies in man. The endogenous compound
      adenosine has various modulatory effects in the peripheral and central nervous
      system, mediated through specific cell-surface associated receptors. The current
      view is that adenosine receptors of the A1-subtype are associated with a
      modulatory effect on pain transmission at spinal cord level. Animal studies have
      repeatedly demonstrated adenosine- and adenosine analog mediated inhibitory
      influences on presumed nociceptive reflex responses (1,2). These examinations in
      rodents have tested acute pain models involving tactile, pressure and heat
      stimulations. More recently, animal lesion models presumably reflecting chronic
      pain, has shown that adenosine analogs can suppress nociceptive behaviour both by
      systemic and intrathecal (i.t.) administration (3,4). Consequently, there is
      substantial evidence that adenosine can modulate nociceptive input. Further, it
      has been proposed that endogenous adenosine formation is involved in
      physiological pain control at the spinal cord level and that its release is
      involved in the action of opioid antinociception (1). Clinical studies have
      revealed that adenosine administration by bolus injection or by infusion at doses
      above 70 micrograms x kg-1 x min-1 is associated with pain symptoms from
      different parts of the body. This algogenic effect of higher doses of adenosine
      is probably related to sensitization/activation of peripheral nociceptive
      afferents (5).

PMID- 9248566
TI  - "Thermodilution"--a flawed method for the measurement of cardiac output.

PMID- 9248567
TI  - Enteral or parenteral nutrition?

PMID- 9248568
TI  - Enteral or parenteral nutrition? Pro-enteral.
AB  - There is a convincing evidence for the superiority of enteral nutrition as
      compared with parenteral In critically ill and injured patients. The general
      objectives of providing nutritional support in the critically ill is to persevere
      body functions that are functioning normally and to facilitate recovery of those
      that are failing. The specific objective for enteral nutrition is, however,
      preservation and restoration of the gastrointestinal structure and function.
      Today, early enteral nutrition is an integral part of the acute management of
      critically ill patients. It is no longer a therapy which can be started "if"
      necessary just to prevent malnutrition. Early enteral nutrition can be
      successfully carried out in virtually all critically ill patients also after
      major abdominal surgery and in acute pancreatitis. There are very few
      contraindications for using enteral nutrition and severe complications are rare.
      Parenteral nutrition, on the other hand, is associated with increased incidence
      of infectious complications and is rarely indicated in critically ill patients.

PMID- 9248569
TI  - Enteral or parenteral nutrition? Pro-parenteral.

PMID- 9248570
TI  - Anesthesia and surgery influences regional net release and uptake rates of tissue
      type plasminogen activator. An experimental study in the intact pig.

PMID- 9248571
TI  - A new method to evaluate central sensitization to pain following surgery. Effect
      of ketamine.

PMID- 9248572
TI  - Is residual neuromuscular block following pancuronium a risk factor for
      postoperative pulmonary complications?

PMID- 9248573
TI  - Effective systemic blockade of endogenous nitric oxide production results in
      moderate hypertension, reduced sympathetic activity and shortened bleeding time
      in healthy volunteers.

PMID- 9248574
TI  - Endogenous nitric oxide in the upper airways of different animal species.

PMID- 9248575
TI  - Peroxidase activity in shoot apical meristem from Spinacia.
AB  - Peroxidase activity was localized in the shoot apical meristem (SAM) of Spinacia
      at the light and electron microscope level with the histochemical method
      employing H2O2 and 3,3'-diaminobenzidine. At the light microscopic level,
      peroxidase activity was examined in unfixed cryostat sections at different pHs.
      The enzyme was found to be more intense at low than at neutral and high pH. The
      activity was evenly distributed over the different regions of the meristem at low
      pH, whereas it was more intense in the rib meristem at pH 6.8 and 7.2. At the
      ultrastructural level, peroxidase activity was found at 3 cellular sites: the
      cell wall, the tonoplast and the plasmalemma. These results were discussed in
      relationship with the in situ distribution of peroxidases in plant cells and
      other enzymes in vegetative SAM.

PMID- 9248576
TI  - Immunohistochemical expression of atrial natriuretic peptide (ANP) in the
      conducting system and internodal atrial myocardium of human hearts.
AB  - Expression and distribution of atrial natriuretic peptide (ANP) were studied
      immunohistochemically in the conducting system and internodal atrial myocardium
      of 5 adult human hearts. Myocytes from the sinus node and compact
      atrioventricular node were usually ANP-negative; only a very few cells exhibited
      ANP immunoreactivity. These ANP-positive myocytes were small and did not appear
      to be trapped working atrial myocytes which are larger than nodal cells. The
      transitional cell zones of the sinus node and the atrioventricular node were
      composed of bundles of ANP-positive myocytes, intermingled with non-reactive
      myocytes. The internodal atrial myocardium exhibited a comparable intensity of
      myocyte staining in each case examined. Thus, morphologically distinct connecting
      pathways between the sinus node and the atrioventricular node with regard to
      myocyte ANP immunoreactivity could not be demonstrated, reinforcing the notion
      that they actually do not exist. The penetrating bundle, branching bundle and
      bundle branches were usually composed of ANP-negative myocytes although some ANP
      positive myocytes were observed in the branching bundle and bundle branches in 4
      cases. Myocytes from the ventricular conducting tissue presenting ANP
      immunoreactivity have been designated Purkinje fibers and have been found in
      several mammalian species.

PMID- 9248577
TI  - New cationic fluorochromes from diaryloxazole scintillators: fluorescence of
      chromatin DNA induced by N-quaternary POPOP derivatives.
AB  - N-quaternary derivatives of the diaryloxazole scintillators POPOP and dimethyl
      POPOP (dmPOPOP) in chloroform solution were obtained by methylation with
      dimethylsulfate. After drying, aqueous solutions of the corresponding oxazolium
      compounds (Q-POPOP and Q-dmPOPOP) revealed strong fluorescence (peaks at 485 and
      493 nm, respectively). Under 365 nm excitation, both N-quaternary derivatives
      induced a bright greenish blue fluorescence in nuclei of chicken erythrocytes and
      human buccal cells, as well as in the kinetoplast DNA of Trypanosoma cruzi
      epimastigotes; mouse mast cell granules showed a green-yellow metachromatic
      emission. Chromatin fluorescence was dependent on the presence of DNA; it was
      abolished by washing with a 10 mM solution of the bisguanidine compound
      Phenformin, whereas 1 M NaCl or MgCl2 had no effect. The oxazolium derivatives
      were hydrophilic (log P: -6.409 and -5.373 for Q-POPOP and Q-dmPOPOP,
      respectively). Molecular modelling studies revealed that these cationic and non
      rigid (cis) scintillator derivatives are well suited to locate along the convex
      floor of the narrow DNA minor groove from adenine-thymine regions.

PMID- 9248578
TI  - The effect of microtubule and microfilament-disrupting drugs on prolactin
      stimulated progesterone synthesis and secretion by cultured porcine theca cells.
AB  - The effect of microtubule- and microfilament-disrupting drugs (colchicine,
      cytochalasin B and D) on basal and prolactin (Prl)-stimulated progesterone
      synthesis and secretion was studied. Microtubules were visualized
      immunocytochemically using a monoclonal antibody against the alpha-subunits of
      tubulin, while microfilaments were detected using a polyclonal antibody against
      actin. The second antibody was conjugated with FITC. Progesterone, androgen and
      estradiol concentration were detected in tissue and culture medium by appropriate
      radioimmunoassays. In Prl-treated cultures microtubules formed a network with
      more radial organisation than in the controls. After colchicine-treatment the
      cells were round, regular in shape and microfilaments were disintegrated and
      replaced by punctate aggregates. Actin filaments formed typical stress fibers in
      theca cells (Tc). In Prl-treated cells some microfilaments were broken resulting
      in a diffuse immunofluorescent pattern. After treatment with cytochalasin B and D
      many of the stress fibers disappeared, the cells became rounded and diffuse
      microfilaments were seen. Prl added to the culture medium increased synthesis of
      all investigated steroids and additionally stimulated progesterone secretion.
      Exposure of theca cells to colchicine caused an increase of basal progesterone
      secretion into the incubation medium which simultaneously decreased the steroid
      content in the cells. Colchicine suppressed Prl-stimulated synthesis of all three
      steroids studied and did not have any effect on their secretion. Exposure of
      theca tissue to cytochalasin B increased basal progesterone and androgen
      synthesis but drastically decreased basal estradiol synthesis by these cells. The
      opposite effect was observed after the addition of cytochalasin D, when estradiol
      synthesis increased and progesterone and androgen synthesis by theca cells was
      not affected. Microtubule and microfilaments-disrupting drugs had no effect on
      the secretion of the investigated steroids in Prl-treated cells. Our results
      suggest that microtubules and microfilaments are involved in Prl-stimulated
      steroid synthesis but not in steroid secretion.

PMID- 9248579
TI  - Colocalization of calretinin and glucagon in rat pancreatic A cells.
AB  - Calretinin is a calcium-binding protein whose major functions are assumed to be
      buffering, transport of Ca2+, regulation of various enzyme systems and cellular
      protection. Moreover, calretinin does not seem to be a specific marker for any
      particular cell since it has been discovered in various mammalian and avian
      organs. In order to give clue to its function(s), we investigate its distribution
      in the rat pancreas using immunocytochemistry and transmission electron
      microscopy. We have found calretinin immunoreactive cells in rat pancreas only in
      the islets of Langerhans. These cells correspond to A cells producing glucagon.
      The colocalization of calretinin and glucagon was confirmed with double-labelling
      immunofluorescence. Nevertheless, the role of calretinin and its relationship
      with the production and/or the exocytosis of glucagon granules remains to be
      elucidated.

PMID- 9248580
TI  - Immunocytochemical study of parafollicular cells of the thyroid and
      ultimobranchial remnants of the European bison.
AB  - The aim of the present study was to compare parafollicular cells in the bison
      thyroid and its ultimobranchial remnants. The thyroid of 26 European bisons was
      fixed in Bouin's fluid, 5 microns thick paraffin sections were stained with
      hematoxylin and eosin. Azan or silver Grimelius methods. For immunocytochemical
      analysis specific rabbit antisera were used against human calcitonin (CT), human
      calcitonin gene-related peptide (CGRP), bovine (b) or rat (r) neuron-specific
      enolase (NSE), human synthetic somatostatin (ST), and porcine chromogranin.
      Strongly positive reactions in the majority of parafollicular cells were observed
      after application of antisera against CT, CGRP, bNSE and rNSE only. ST
      immunopositive cells were found in small numbers. Immunopositive parafollicular
      cells were also present outside typical structures of the thyroid within
      persistent ultimobranchial remnants. In persistent ultimobranchial bodies,
      parafollicular cells were frequently observed in groups between ultimobranchial
      follicles in form of solid cell nests. Many of these cells did not react with any
      of the antisera used and showed features of immature cells. It is concluded that
      histomorphologic analysis and immunocytochemical examination reveals a
      heterogeneous population of parafollicular cells in the bison thyroid, and this
      heterogeneity was particularly clear in persistent ultimobranchial bodies.

PMID- 9248581
TI  - Intracellular localization of inducible nitric oxide synthase in neonatal rat
      cardiomyocytes in culture.
AB  - Recognition of the role of nitric oxide (NO) in cardiovascular regulations raised
      an acute interest in NO-generating enzymes-nitric oxide synthases (NOS).
      Nevertheless, the subcellular localization of inducible isoform of NOS (NOS II)
      and regulation of its expression in the cardiomyocyte still remains to be
      elucidated. Therefore, we focused this study on the subcellular localization of
      NOS II in cultured neonatal rat cardiomyocytes using immunocytochemical
      techniques at the light and electron microscopic level as well as the
      demonstration of NADPH-diaphorase activity and the Griess assay for NO
      measurement. Cultivation of neonatal cardiomyocytes during 2 and more days
      induced a moderate increase in the NOS II immunolabeling in defined cytoplasmic
      structures and a nuclear NOS II staining in some cells. Exposure of the cell
      cultures to exogenous cAMP markedly stimulated NO production with a concomitant
      enhancement of NOS II immunolabeling of cardiomyocytes. cAMP-induced changes were
      significantly attenuated by dexamethasone. This report provides evidence for the
      localization of NOS II in the perinuclear space, Golgi complex, mitochondria,
      plasma membrane and along contractile fibers of cardiomyocytes, as well as for
      the appearance of NOS II staining of the cell nuclei in the course of
      cultivation. In non-cardiomyocytes contaminating the cell culture, positive
      immunoreaction was detected in the Golgi complex and endoplasmic reticulum. Our
      data point to a notable constitutive expression of NOS II in rat cardiomyocytes
      apparently dependent on the developmental stage.

PMID- 9248582
TI  - Arteriovenous malformations of the basal ganglia region: rationale for surgical
      management.
AB  - Surgical indications for arteriovenous malformations (AVMs) arising at the region
      of the basal ganglia are questionable and the majority of cases are considered
      inoperable. Albeit not free from risks of morbidity and mortality, the treatment
      of choice is usually radiosurgery for small lesions, and embolization plus
      radiosurgery for larger lesions. Nevertheless, some lesions may be amenable for
      surgical resection due to their favorable location. Eighteen cases of such AVMs
      were selected for a direct approach in our series. Seventeen cases were
      classified as Spetzler and Martin [22] grade III, and one case was a grade V. Ten
      patients were males and eight females. The mean age was 28.3 years (ranged from 2
      to 43 years). Sixteen patients had had previous hemorrhagic events prior to
      hospital admission. Eleven patients had pre-operative well established
      neurological deficits, and seven patients although symptomatic had a normal
      neurological exam at admission. Fifteen patients had their AVMs completely
      resected. Among the eleven patients with previous neurological deficits nine had
      no change in their pre-operative condition and two experienced postoperative
      neurological worsening. In the long-term follow-up six patients had a complete
      recovery and five recovered only partially. Among the seven patients whose
      neurological examination was normal pre-operatively five remained unchanged, one
      had a transient motor deficit, and one died due to a thalamic venous infarction
      and massive bleeding into the thalamus. The anatomical knowledge and the precise
      localization of the arteriovenous malformation through the aid of neuroimage
      studies has provided the means to classify these AVMs and plan operative
      strategies for some small selected cases with relatively low morbidity.

PMID- 9248583
TI  - Is there a group of early surgery aneurysmal SAH patients who can expect to
      achieve a complete long-term neuropsychological recovery?
AB  - There is a significant controversy regarding the effect of early surgical
      intervention for microsurgical aneurysm clipping on long-term cognitive recovery.
      Although new strategies in surgical and medical management have progressively
      reduced the morbidity and mortality rates related to subarachnoid haemorrhage
      (SAH), the overall quality of life of aneurysm patients has been reported to
      remain unsatisfactory. In fact, even in the presence of a good neurological
      recovery following an aneurysmal SAH, patients may show persistent emotional and
      psychological disturbances. The aim of this study was to analyse the long-term
      cognitive, neuropsychological and emotional status of a group of patients,
      subjected to early surgery aneurysm treatment, and having SAH characteristics
      generally considered predictive of a favourable outcome. Patients were submitted
      to a complete battery of neuropsychological tests designed to assess a full range
      of cognitive and attentional functions. The results of the neuropsychological
      evaluation did not detect evidence of any significant cognitive deterioration as
      compared to control volunteers and to the published age-adjusted test norms.
      These results indicate that early aneurysm surgery, coupled with modern
      microneurosurgical techniques and aggressive medical management is associated
      with a good neurological outcome and a full recovery of cognitive,
      neuropsychological and emotional performances in a subset of patients with
      favourable clinical characteristics.

PMID- 9248584
TI  - Local spread of malignant neuroepithelial tumors.
AB  - A short review of invasiveness of primary malignant neoplasms in the nervous
      system is given. Invasiveness implies progressive spread and destruction locally,
      which eventually leads to a fatal outcome in the patient. In particular, the
      malignant cells are able to rapidly migrate over large parts of the brain. This
      process includes the capacity to adhere to a substratum, usually constituted by
      the various components of the extracellular matrix, followed by detachment and
      migration. Anatomical structures and local regulatory factors in the brain
      influence the direction and extent of this migration. Several model systems are
      now available for monitoring the aggressiveness of such tumours both in vivo and
      in vitro, and different phenotypic properties characteristic of invasive cells
      have been elucidated. Although still in its infancy, and currently as an
      experimental approach, anti-invasive therapy may in the future be an interesting
      alternative to conventional chemotherapy of brain tumours.

PMID- 9248585
TI  - Sellar tuberculoma: report of two cases.
AB  - Hypophyseal tuberculomas are exceptionally rare. We report two patients with
      sellar tuberculoma but with no evidence of concurrent extrasellar disease.
      Although the lesion is often mistaken for adenoma, there are characteristic
      radiological features: intense enhancement on contrast CT and thickening of the
      pituitary stalk on MRI in 86% of cases. Accurate diagnosis is important because
      pituitary tuberculoma is curable.

PMID- 9248586
TI  - Primary spinal epidural non-Hodgkin's lymphomas in childhood: a review of 6
      cases.
AB  - We report a retrospective study regarding 6 children with primary epidural non
      Hodgkin's lymphomas and analyse the factors influencing prognosis with emphasis
      on treatment. Four patients were females and 2 males. The neurological condition
      of patients was assessed pre- and postoperatively according to Shaw's
      classification for neurological disability. All patients were submitted to
      surgery, radiotherapy and chemotherapy. Histologically, the tumour proved to be a
      high-grade non-Hodgkin's lymphoma in all cases. At follow-up, all patients are
      alive after a median interval of 52 months (range 24-72 months). This study
      showed that the outcome of patients depends on the gravity of pre-operative
      deficits whereas the survival is influenced by the type of treatment.

PMID- 9248587
TI  - Surgical technique for cranio-cervical decompression in syringomyelia associated
      with Chiari type I malformation.
AB  - Our purpose is to present our results with the surgical treatment of
      syringomyelia associated with Chiari type I malformation. Between October 1989
      and October 1995, twenty-eight patients underwent a sub-occipital craniotomy and
      a C1 laminectomy. After dura mater opening the cerebellar tonsils were mobilised.
      Neither catheter, nor plugging of the obex, nor tonsillar tissue removal was
      performed. The dura mater was enlarged by means of a wide graft to create a new
      cisterna magna of adequate size. Postoperative MRI scans showed an ascent of the
      cerebellum of 4.3 +/- 4.8 mm (measured by the fastigium to basal line), as well
      as of the brainstem (mean migration of the mesencephalon-pons junction of 4.3 +/-
      3.3 mm). The tonsils emigrated cranially 6.5 +/- 4.8 mm. While preoperative mean
      syringo-cord ratio was 66.3% +/- 13.3, post-operatively was 12.1% +/- 12.7 (p <
      0.0001). A complete collapse of the syrinx was observed in 39% of the patients.
      Long-term improvements were obtained in 73% of the cases and 27% were unchanged.
      No patient got worse. We conclude that in the treatment of syringomyelia
      associated with Chiari I malformation an artificial cisterna magna of sufficient
      size must be created. This is achieved by means of an extensive sub-occipital
      craniotomy and C1 laminectomy, followed by dural opening. Small bone removal with
      limited enlargement of the posterior fossa often results in failures of treatment
      and recurrences. Tonsillar removal is not necessary to obtain a good
      reconstruction of the cisterna magna.

PMID- 9248588
TI  - Intradiscal glycerol or bupivacaine in the treatment of low back pain.
AB  - A total of 15 patients suffering from chronic low back pain were treated with an
      intradiscal injection of either 1 ml of 50% glycerol or 2 ml of 0.5% bupivacaine.
      Most (60%) of the patients had previously undergone spinal surgery for lumbar
      disc herniation or spinal stenosis and 73% showed clinical signs and symptoms of
      segmental instability of the lumbar spine. According to self-evaluation
      questionnaires, immediate response to both treatments was mainly good. Of the 9
      patients who received glycerol, 56% showed subjective improvement on the first
      day after the injection and after two weeks, 45% of the patients still felt
      improvement. After one month, however, the pain had reappeared in all except one
      (11%) patient. The corresponding numbers for the 6 with bupivacaine treated
      patients were 83%, 67%, and 17%. Based on the very short duration of response to
      the treatment, we did not find intradiscal injections with these agents to be
      cost-effective. In our department, this therapeutic approach is no longer
      employed in patients with chronic discogenic pain.

PMID- 9248589
TI  - The effect of condylectomy on extreme lateral transcondylar approach to the
      anterior foramen magnum.
AB  - The dorsolateral, suboccipital, transcondylar technique was used in this
      cadaveric study. The angle and distance measurements in the corridors were taken
      intradurally both superior and inferior of the foramen magnum level. In the first
      stage of this study, the findings which were gained from the standard lateral
      suboccipital approach were compared with the findings after condyle and lateral
      atlantal mass removal. After condylectomy, the approach to anterior foramen
      magnum via both corridors was found to be shorter and the lateral angle of the
      exposure of the anterior foramen magnum was found to be wider. The considerable
      shortening of the distances to the anterior foramen magnum, especially in the
      superior corridor, emphasises the necessity of combining standard approaches with
      condylectomy. In addition, it was found that after condylectomy, considerable
      widening of both transverse and longitudinal planes in the inferior corridor
      allows the surgeon greater access to work on lesions. Furthermore, the freed
      space between the superior corridor and the interior corridor, which was gained
      by condylectomy, shows that condylectomy provides a combined approach to the
      inferior and superior parts of the foramen magnum anteriorly.

PMID- 9248590
TI  - Frameless stereotactic guided neurosurgery: clinical experience with an infrared
      based pointer device navigation system.
AB  - An infrared based frameless stereotactic navigation device (Easy Guide Neuro) was
      investigated for its clinical applicability, registration/application accuracy
      and limitations in a standard operating room set-up. In a five-month period 40
      frameless stereotactic procedures (23 female, 17 male, mean age 46.4, yrs range
      10-83) including 36 craniotomies and 4 spinal surgery procedures were performed.
      Image registration, data transfer and operation planning using skin fixed
      fiducials (between 5-10, mean 6.6) and CCT in 12 patients/MRI in 28 patients,
      generally was done the day before surgery. Clinical applicability was proven in
      all procedures with an additional time for pre-operative imaging and system
      application in the OR of 50 min mean (35-120 range). A useful registration was
      achieved in 39/40 patients (97.5%) with a registration accuracy of 3.4 mm (range
      1.8-6.7) for brain surgery cases and 14.4 mm (6.8-25) for spine cases. This
      resulted in intra-operative application accuracy values for brain surgery of 4.2
      mm mean (range 1-12). Enhanced registration/application accuracy values over the
      test period from 4.2/3.8 mm mean (Cases 1-20) up to 3.2/2 mm mean (Cases 21-40)
      was observed. In spinal surgery an application accuracy of 11.3 mm mean (range 5
      20) was found. An intra-operative re-calibration because of system-head drift was
      necessary in none of the patients, nevertheless, application accuracy degradation
      due to brain shift was detected in every case. In conclusion, the system allowed
      a time sufficient accurate frameless intra-operative localisation guidance in
      cavernoma, meningioma, glioma, and brain metastasis surgery. In spinal surgery,
      the application accuracy exceeded clinical usefulness due to high registration
      inaccuracy using skin markers.

PMID- 9248591
TI  - Connective tissue reactions in subdural haematomas: imaging with contrast
      enhancement MRI.
AB  - The sensitivity of contrast enhanced magnetic resonance imaging (MRI) in the
      detection of connective tissue reactions accompanying the maturation of subdural
      haematomas (SDH) was studied. An outer enhancing layer between the SDH and the
      tabula interna of the vault was shown in 16 out of 17 cases. In early SDH this
      outer enhancing layer presumably is due to vascular congestion and/or increased
      vascular permeability. A thickening of the outer enhancing layer and/or an inner
      enhancing layer between the haematoma and the subarachnoid space was visible in 9
      patients and represented a haematoma capsule formed by proliferating granulation
      tissue. In 5 SDH septations were found, 3 SDH consisted almost completely of
      enhancing granulation tissue. Thus, contrast enhanced MRI delivers additional
      information about the structure of SDH, which are useful for determining the
      extent of surgical treatment especially in chronic SDH.

PMID- 9248592
TI  - Fluid-attenuated inversion recovery (FLAIR) in a patient with parasagittal white
      matter shearing injury.
AB  - We present a 32-year-old woman with a parasagittal white matter shearing injury
      of the left frontal lobe following a motor vehicle collision. There was
      monoplegia of the right lower extremity. Computed tomography failed to
      demonstrate the lesion which was visible on magnetic resonance images. In
      particular, fluid-attenuated inversion recovery images were useful to depict the
      shearing injury, since sulci were of low intensity on those images.

PMID- 9248593
TI  - ICP monitoring with a re-usable transducer: experimental and clinical evaluation
      of the Gaeltec ICT/b pressure probe.
AB  - Intracranial pressure monitoring requires reliable transducers at a justifiable
      price. At present, transducers for single or repeated use are available. We
      examined the Gaeltec model ITC/b solid state miniature transducer experimentally
      and clinically. Measurement accuracy was assessed in vitro at increasing steps of
      5 mmHg from 0 to 80 mmHg. While new and recently serviced probes revealed minimal
      deviations from the preset values, frequently used transducers differed up to 7
      mmHg. This occurred especially in the high pressure range above 50 mmHg.
      Additionally the drift was investigated at different pressure levels. After 24
      hours we already found drifts of 2 mmHg with new and serviced probes and up to 4
      mmHg with used ones. In clinical practice we implanted 150 transducers in 121
      patients from 1983 until 1995. The probes were re-used up to twelve times, the
      average time being 7 times. 32.7% of all measurements were regarded as not
      reliable. Dislocation (16.7%), inability to calibrate (3.3%) and defect pressure
      probes (3.3%) were the most common complications. Repeated use of the Gaeltec
      ICT/b probe also seemed to result in an additional decay of measurement quality.
      The strain of frequent cleaning and sterilizing may have caused changes of the
      physical properties of the probes with time. Whether these results also apply to
      other types of ICP probes for repeated use needs further evaluation.

PMID- 9248594
TI  - Interactions between vasoconstrictors in isolated human cerebral arteries.
AB  - This study investigates whether different endogeneous vasoconstrictors exert
      synergistic effects in isolated human cerebral arteries, because potentiation of
      contractile effects may play a role in the pathogenesis of cerebral vasospasm.
      Isolated human pial arteries obtained from macroscopically intact tissue during
      brain tumour operations were mounted onto a wire myograph. Concentration-response
      curves of 5-hydroxytryptamine (5-HT) were constructed in the absence and presence
      of threshold concentrations of the thromboxane A2 (TXA)-analog U46619, and
      endothelin-1 (ET-1). Threshold concentrations of U46619 markedly enhanced the
      maximum contractile effect of 5-HT. The response to 5-HT remained markedly
      increased even after washout of U46619. Threshold concentrations of ET-1
      increased the maximum response to 5-HT, and markedly shifted the dose-response
      curve to the left. Even after washout of ET-1, the dose-response curve of 5-HT
      remained shifted to the left. The increase of the contractile effect of 5-HT in
      the presence of U46619 did not correlate with the relaxant action of the
      endothelium-dependent vasodilator carbachol. Thus, synergism between contractile
      substances such as 5-HT, U46619, or ET-1 is seen in human cerebral arteries, and
      responses to 5-HT are potentiated even after washout of ET-1 and U46619. The
      potentiation does not depend on the endothelial function. We conclude that
      synergistic responses between endogeneous vasoconstrictors such as 5-HT, TXA and
      ET-1 may be involved in the pathogenesis of cerebral vasospasm after subarachnoid
      haemorrhage.

PMID- 9248595
TI  - Remote hemorrhage of a pontine cavernous angioma fifty-two years after cerebral
      irradiation.

PMID- 9248596
TI  - Atretic cephalocele in the adult.
AB  - Atretic cephaloceles are usually detected at birth. Recently we treated a 38-year
      old man with one of these lesions, apparently the first report of this occurrence
      in an adult.

PMID- 9248597
TI  - Ardeparin cleared for marketing.

PMID- 9248598
TI  - Protease inhibitors may raise blood glucose levels, FDA warns.

PMID- 9248600
TI  - Planning for an ambulatory care service.

PMID- 9248599
TI  - FDA proposes constraints on ephedrine dietary supplements.

PMID- 9248601
TI  - Pharmacist influence on economic and morbidity outcomes in a tertiary care
      teaching hospital.
AB  - The influence of pharmacist participation on economic and morbidity outcomes at a
      tertiary care teaching hospital was studied. Patients admitted to internal
      medicine wards during a nine-month period were assigned to either a treatment
      team or a control team. Each team consisted of an attending physician, senior and
      junior medical residents, and medical students; the treatment team included a
      pharmacist who reviewed all patient charts, made rounds with the team, and
      recommended modifications of drug therapy. Pharmacy interaction with the control
      team was limited to contacting physicians about potentially dangerous orders,
      answering questions from the medical team, and handling orders for items not on
      the formulary or otherwise unavailable. After discharge, data from patient
      records were analyzed for pharmacy costs and total hospital costs and length of
      stay (as markers of the pharmacist's effect on economics and morbidity,
      respectively). Analysis of baseline characteristics showed that the two groups of
      patients were statistically comparable. Treatment team patients who were included
      in the data analysis (414) had significantly shorter stays (by a mean of 1.3
      days) and lower pharmacy and total hospital costs (by a mean of $301 and $1654,
      respectively) than those included in the control team analysis (453). The direct
      participation of a pharmacist on a patient care team significantly decreased
      pharmacy and hospital costs, as well as length of stay, compared with minimal
      participation of a pharmacist.

PMID- 9248602
TI  - Reliability and validity of hospital pharmacists' clinical intervention data.
AB  - The reliability and validity of pharmacist intervention data documented at a
      hospital in England were studied. The study involved intervention data recorded
      from September 1 to December 31 in 1990 (a pilot study), 1991, and 1992 by a
      total of 23 pharmacists. The interventions in 1990 were coded by a single
      pharmacist manager and compared with coding by pharmacists of their own
      interventions during 1991 and 1992. To test for internal reliability of the
      intervention data, 25% (584) of the 2342 interventions recorded in 1991 and 1992
      were randomly sampled after interventions by the 11 pharmacists no longer at the
      site were eliminated. In September 1993 the 12 remaining pharmacists were asked
      to recode the interventions they had previously entered. In March 1994 a panel of
      12 pharmacists recoded 62 interventions randomly selected from the 684 recoded
      interventions. Each panel member also assigned financial values to interventions.
      Medical records corresponding to the 62 recoded interventions were inspected for
      evidence of the interventions. The distribution of interventions among the drug
      use-process (DUP) indicators used in the coding differed significantly between
      1990 (when a manager assigned all codes) and 1991 plus 1992 (when pharmacists
      coded their own interventions). There were similar differences between 1991 and
      1992. Results from code-recode and panel testing showed the DUP indicators to be
      reliable. Clinical outcome indicators were unreliable, as were financial
      indicators. Medical records verified the occurrence of 50 (81%) of the 62
      interventions selected, but in only one case was there evidence that the change
      in drug therapy was initiated by a pharmacist. The capacity of pharmacists at a
      British hospital to reliably code interventions was poor.

PMID- 9248603
TI  - Handling of gene-transfer products by the National Institutes of Health Clinical
      Center pharmacy department.
AB  - Policies and procedures for handling gene-transfer products at the National
      Institutes of Health (NIH) Clinical Center pharmacy department are described. The
      pharmacy at the Clinical Center is responsible for handling in vivo gene-transfer
      delivery systems, which are gene-transfer products that are prepared for direct
      administration to patients. The gene-transfer products currently handled by the
      pharmacy are investigational and are composed of viruses containing the gene
      encoding either of the melanoma antigens MART-1 and gp100. The pharmacy has
      prepared guidelines, based on the principles of aseptic technique and FDA
      guidelines for manufacturing facilities, intended to help pharmacy personnel
      safely dilute a concentrated gene-transfer product into a dose suitable for
      administration. Before a product is handled, the biological safety level is
      determined and a biohazard sign is posted. Worksheets detailing all supplies,
      calculations for dilutions, and procedures that will be required are prepared in
      advance; the worksheets are part of a drug fact sheet prepared for all
      investigational drugs dispensed. Personnel must be properly trained and dressed
      in protective clothing. Aseptic technique and decontamination procedures are used
      as specified in the guidelines, and all materials used are disposed of as
      biohazardous waste. All work is documented. If a worker is accidentally exposed,
      standard procedures are followed. The handling of gene-transfer products at the
      NIH Clinical Center pharmacy is based on the principles of aseptic technique, FDA
      guidelines, and experience.

PMID- 9248604
TI  - Accuracy of technicians versus pharmacists in checking syringes prepared for a
      dialysis program.
AB  - The accuracy of pharmacy technicians versus pharmacists in checking drug doses
      prepared in syringes for a dialysis program was studied. Three pharmacy
      technicians from the pharmacy of a regional kidney disease program in Minnesota
      participated in the study after completing a training program and after common
      preparation errors had been identified by pharmacists. From November 1995 to
      April 1996, the technicians used labels printed from a database of pharmacist
      verified orders to prepare and label i.v. syringes. Four medications were used
      epoetin alfa, calcitriol, heparin prepared from beef lung, and heparin prepared
      from porcine intestinal mucosa. Each syringe was checked by one of nine
      pharmacists for accuracy of dose and medication, and all errors were recorded.
      The technicians checked syringes prepared by other technicians and also recorded
      errors. Accuracy rates (percentages of syringes correctly evaluated) for
      pharmacists and technicians were compared. A total of 10,608 syringes were
      checked. Accuracy rates for pharmacists and pharmacy technicians were 99.86% and
      99.83%, respectively. Accuracy rates in checking syringes did not differ
      significantly between pharmacists and technicians in this study setting.

PMID- 9248605
TI  - Cost comparison of single daily i.v. doses of ceftriaxone versus continuous
      infusion of cefotaxime.
AB  - The costs of administering ceftriaxone 1 g in a once-daily 30-minute infusion
      were compared with the costs of administering cefotaxime 2 g/day (with an
      additional 1 g given on day 1) by continuous intravenous infusion. Time and
      motion studies were conducted to determine the pharmacy and nursing labor
      required to prepare and administer the intermittent and continuously infused
      antimicrobials. Mean times were multiplied by the mean New England hourly wage
      for pharmacy technicians, pharmacists, and nurses to determine the total labor
      costs of each regimen. Hospital acquisition costs of items used in preparing
      antimicrobial doses for administration by each method were also compared.
      Wholesale acquisition costs of the two drugs were used in the analysis. Labor
      costs were higher for the continuously infused antimicrobial because of the
      additional nursing time required for monitoring. Supply costs were greater for
      continuous infusion. Drug acquisition cost was the major component of the overall
      cost of therapy and was lower for continuous infusion. A cost analysis showed
      that continuous i.v. infusion of cefotaxime 2 g/day was less expensive from day 2
      onward than intermittent daily i.v. doses of ceftriaxone 1 g.

PMID- 9248606
TI  - Stability of sumatriptan succinate in extemporaneously prepared oral liquids.
AB  - The stability of sumatriptan succinate in extemporaneously prepared oral liquids
      was studied. Suspensions of sumatriptan (as the succinate salt) in Ora-Sweet, Ora
      Sweet SF, and Syrpalta syrups (Paddock Laboratories and Humco Laboratory) were
      extemporaneously compounded to produce a sumatriptan concentration of 5 mg/mL.
      Each suspension was prepared in triplicate. The suspensions were stored at 4
      degrees C in amber glass bottles for 60 days. Two 1-mL samples were removed from
      each bottle initially and on days 2, 7, 14, 21, 28, 35, and 60. Sumatriptan
      concentrations were determined by high-performance liquid chromatography. The
      samples also underwent visual inspection and microbial testing. The mean
      concentration of sumatriptan in all suspensions remained above 90% of the initial
      concentration for up to 21 days. By day 28, the sumatriptan concentration of all
      suspensions had decreased to less than 90% of the initial concentration. None of
      the suspensions had microbial growth up to day 28, and there were no visible
      changes in the suspensions throughout the study period. Sumatriptan 5 mg/mL (as
      the succinate salt) in three oral suspensions was stable for up to 21 days when
      stored without light at 4 degrees C.

PMID- 9248607
TI  - Comparison of manual and bar-code systems for documenting pharmacists'
      interventions.

PMID- 9248608
TI  - Accuracy of drug allergy documentation.

PMID- 9248609
TI  - FDA position on product selection for 'narrow therapeutic index' drugs.

PMID- 9248610
TI  - USP standards and activities affecting pharmacy practice.

PMID- 9248611
TI  - Measuring human immunodeficiency virus type 1 RNA viral load.

PMID- 9248612
TI  - Fact versus opinion in the judgment on fosphenytoin articles.

PMID- 9248613
TI  - Fact versus opinion in the judgment on fosphenytoin articles.

PMID- 9248614
TI  - The frequency of QAP2.1 is increased in psoriasis vulgaris patients but no
      unusual linkage between QAP/DQA1 or QBP/DQB1.
AB  - Psoriasis vulgaris is a chronic skin disease with a genetic and immunological
      background. We have previously defined the two most frequent risk haplotypes in
      Finns: A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201. The aim of this
      study was to further examine whether the flanking regions, URRs of DQ (QAP and
      QBP) and TAP1 and TAP2 genes are involved in susceptibility to psoriasis. The
      frequency of QAP2.1 was increased in psoriatics as compared with controls (Pc =
      3.6 x 10(-2), RR = 5.0), and the frequency of QAP4.1 was decreased in psoriasis
      patients (Pc = 4.2 x 10(-2)). The frequency of the phenotype combination Val/Ile
      at position 379 of TAP2 was decreased in patients (Pc = 1 x 10(-2)). The allele
      and phenotype frequencies of TAP1 and TAP2 genes were not different between these
      groups. Haplotypes A2, B13,Cw6,DR7,DQA1*0201,QAP2.1 and A1,B17,Cw6,
      DR7,DQA1*0201,QAP2.1 are the two most frequent HLA marker haplotypes for
      psoriasis vulgaris in Finns, Cw6, DR7, DQA1*0201 and QAP2.1 being the most
      important single alleles for the risk of this disease.

PMID- 9248615
TI  - Changes in the distribution of actin-associated proteins in psoriatic
      keratinocytes. Immunohistochemical study using confocal laser scanning
      microscopy.
AB  - Recent studies support the presence of adherens junctions at the dermal-epidermal
      interface in addition to hemidesmosomes. In this area the integrin/actin
      containing cytoskeleton connection occurs by means of a complex of proteins
      called actin-associated proteins (talin, vinculin, alpha-actinin). As previous
      studies have demonstrated the presence in psoriatic lesions of marked alterations
      in both the basement membrane molecular composition and the polarized expression
      of integrins, we decided to determine whether alterations in the behaviour of the
      actin-associated proteins could be demonstrated. We thus undertook an
      immunolocalization study with monoclonal antibodies directed against talin,
      vinculin, and alpha-actinin in cutaneous biopsies taken from involved and
      uninvolved skin of 12 patients with extensive chronic plaque psoriasis. The
      findings showed an almost total lack of reaction against talin and vinculin in
      the basal layer and an increased positivity against the proteins in the
      suprabasal layers. Similar, though less marked, alterations were present in
      uninvolved psoriatic skin. These results, in agreement with those of previous
      studies, confirm serious alterations in the matrix protein/cytoskeleton
      connection system, and support the hypothesis that this condition may play a key
      role in the pathogenesis of the disease.

PMID- 9248616
TI  - Lesional alopecia areata T lymphocytes downregulate epithelial cell
      proliferation.
AB  - Alopecia areata is characterized by peribulbar infiltration by activated T cells.
      The function of these T cells in the pathogenesis is unknown. To elucidate the
      potential role of lesional T cells in the regulation of hair growth, T-cell
      clones from the margin of involved alopecia areata lesions from three patients
      were obtained by cloning, using the limiting dilution method. Of these T-cell
      clones, 31 were CD4+CD8-, 15 were CD8+CD4- and 2 were CD4-CD8-. The T-cell clones
      were activated and the supernatant harvested 24 h later and tested for its
      capacity to regulate proliferation of neonatal keratinocytes. The majority of the
      T-cell clone supernatants inhibited epithelial cell proliferation in a dose
      dependent fashion. When the cytokine profiles of conditioned T-cell medium were
      compared with the growth-regulatory capacity, it was found that T-cell clones
      that released high amounts of interferon gamma and/or tumour necrosis factor
      alpha inhibited keratinocyte growth. In conclusion, T cells derived from the
      margin of active alopecia areata lesions are able to downregulate epithelial cell
      proliferation. This points to an important role of the immune system, especially
      the T cells, in this disease.

PMID- 9248617
TI  - Experimental induction and ultrastructural characterization of apoptosis in
      murine acute cutaneous graft-versus-host disease.
AB  - The skin is a primary target organ in acute graft-versus-host disease (GVHD).
      Recent results suggest that keratinocytes may undergo apoptosis in acute GVHD,
      although sequential structural evidence supporting this concept is lacking. The
      present study was undertaken to document and characterize apoptosis, confirmed by
      endonuclease-mediated DNA fragmentation, in experimental acute GVHD via
      sequential analysis of ultrastructure. Furthermore, we sought to define whether
      apoptosis is effector cell-dependent or- independent, and to document cell types
      responsible for the scavenging of apoptotic cells. Acute GVHD was produced across
      minor histocompatibility loci using appropriately matched murine strains and
      highly purified preparations of donor CD4+ and CD8+ T-cell subsets. Transmission
      electron microscopy was correlated with in situ labeling of double-stranded DNA
      breaks by the TUNEL (terminal uridine deoxynucleotidyl transferase end ligation)
      technique. Apoptotic cells were observed in all groups receiving T cells.
      Although most apoptotic cells were found in apposition with effector lymphocytes,
      a minority of apoptotic cells were detected at early time-points prior to
      lymphocytic infiltration. Heterogeneous cells, including macrophages,
      lymphocytes, Langerhans cells and keratinocytes were involved in scavenging
      putative target cells undergoing apoptosis. This study confirms the final pathway
      of target cell injury in acute GVHD to be apoptosis. In acute GVHD, apoptosis can
      be induced in the presence or absence of local effector cell influx, suggesting
      at least two mechanisms for the induction of epidermal target cell injury.

PMID- 9248618
TI  - Interleukin-11 production is increased in organ cultures of lesional skin of
      patients with active plaque-type psoriasis as compared with nonlesional and
      normal skin. Similarity to interleukin-1 beta, interleukin-6 and interleukin-8.
AB  - Increased levels of several cytokines, mainly proinflammatory mediators, have
      been reported in psoriatic lesions. Little information, if any, is available
      concerning other cytokines, especially those initially studied as marrow
      differentiation agents. Using the experimental approach of measuring cytokines
      released by skin organ cultures. IL-11 and three other proinflammatory cytokines
      (IL-1 beta, IL-6 and IL-8) were determined using commercially available ELISA
      kits in supernatants of ten biopsies from lesional and nonlesional psoriatic skin
      areas and in supernatants of biopsies from ten normal volunteers. The results
      obtained showed that the amounts of IL-11 and the other three modulators were
      significantly increased in the material from the lesional areas (P < 0.01). The
      amounts of IL-11, which is known to have functional activity similar to the
      proinflammatory cytokines and to share a receptor component with IL-6, were also
      correlated with the disease severity index (R = 0.69, P = 0.04). In addition, a
      nearly significant correlation was noted between the amounts of IL-11 released by
      the lesional and the nonlesional skin biopsies (R = 0.66, P = 0.05). More
      detailed studies are needed to clarify whether IL-11 plays a specific functional
      role in psoriasis, but this study emphasizes the complexity of the pathogenesis
      of psoriasis and the cytokine network, including activation of proinflammatory
      and haemopoietic biological response modifiers, in this disease.

PMID- 9248619
TI  - Mode of action of glycolic acid on human stratum corneum: ultrastructural and
      functional evaluation of the epidermal barrier.
AB  - Alpha-hydroxy acids (AHA) such as glycolic acid have recently been used
      extensively in cosmetic and dermatological formulas. In low concentration (2-5%)
      glycolic acid is believed to facilitate progressive weakening of cohesion of the
      intercellular material of the stratum corneum (SC), resulting in uniform
      exfoliation of its outermost layers (the stratum disjunctum). Since thinning of
      the SC as well as changes of intercellular lipids could theoretically compromise
      the barrier functions of the skin, we investigated the mode of AHA action on the
      SC to determine whether enhanced desquamation compromises the barrier structures
      of the SC and changes transepidermal water loss (TEWL) values. Electron
      microscopy of the epidermis biopsied from the volar forearm of human volunteers
      after 3 weeks of treatment with a 4% glycolic acid formulation twice daily was
      employed to evaluate 1) epidermal morphology and thickness of the SC, (2) the
      lamellar body and SC lipid bilayer organization, and (3) desquamative events
      based on degradation of desmosomes. TEWL values and SC hydration were recorded
      prior to and at the end of the study. Electron microscopy revealed no
      ultrastructural changes in the nucleated layers of the epidermis. The lamellar
      body (LB) secretory system in the stratum granulosum (SG), and intercellular
      lipid lamellae in the SC in both vehicle- and glycolic acid-treated samples were
      comparable to normal human SC. Within the SC, enhanced desmosomal breakdown,
      promoting loss of cohesion and desquamation, was restricted to the stratum
      disjunctum while desmosomes of the stratum compactum were unaffected. Treated
      areas displayed histologically, a more compact appearing SC. TEWL values remained
      unchanged in glycolic acid- and vehicle-treated skin. Our findings indicate that
      the barrier structures of the SC are not disrupted by glycolic acid formulations
      at the concentration used. One of the mechanism of action of AHA on the SC seemed
      to be a "targeted" desmosomal (corneosomal) action without compromising the
      barrier structures of the skin.

PMID- 9248620
TI  - Dehydroepiandrosterone may be one of the regulators of cytokine production in
      atopic dermatitis.
AB  - Previous studies in mice have shown that dehydroepiandrosterone (DHEA) increases
      the production of Th1-associated lymphokines, and of interleukin-2 (IL-2) and
      interferon-gamma (IFN-gamma), by lymphocytes. However, there are no reports
      concerning the effect of DHEA on the production of Th2-associated lymphokines, IL
      4 and IL-5, by lymphocytes in humans. We examined serum DHEA levels in patients
      with atopic dermatitis (AD), which is thought to be associated with a higher
      activity of Th2 cells than of Th1 cells. We also studied the effects of DHEA on
      the production of IL-4 and IL-5 by human lymphocytes. Serum DHEA concentrations
      in 47 adult male patients with AD aged 19-30 years were significantly lower than
      those of 53 age-matched healthy male controls. Preincubation of peripheral blood
      mononuclear cells (PBMCs) with DHEA reduced the IL-4 production by concanavalin A
      stimulated PBMCs. Their IL-5 production also showed a tendency to decrease. These
      results suggest that DHEA may be one of the regulators of IgE synthesis and
      eosinophil proliferation in patients with AD and it may act by controlling IL-4,
      IL-5 and IL-2 production by lymphocytes.

PMID- 9248621
TI  - IRF-1 expression in normal human epidermal keratinocytes.
AB  - Interferon gamma (IFN-gamma) is a potent inducer of cell growth arrest in human
      epidermal keratinocytes. Interferon regulatory factor-1 (IRF-1), an interferon
      inducible gene, is a mediator of interferon action. It has also been suggested
      that IRF-1 may have a functional role as a tumor suppressor gene and may be
      associated with the antiproliferative effect of IFN-gamma. We examined the
      expression of IRF-1 mRNA in normal human epidermal keratinocytes (NHEK). Northern
      blot analysis demonstrated an increased expression of IRF-1 mRNA by IFN-gamma in
      NHEKs. This increased expression of IRF-1 mRNA by IFN-gamma was not blocked by
      treatment with cycloheximide, but was abolished by treatment with actinomycin D.
      In addition, neither pretreatment with TPA, a protein kinase C (PKC) activator,
      nor treatment with H7, a PKC inhibitor, affected the induction of IRF-1 mRNA by
      IFN-gamma. These results indicate that IFN-gamma-induced IRF-1 mRNA in NHEKs is
      transcriptional and PKC-independent.

PMID- 9248622
TI  - Characterization of in vitro culture of HIV-negative Kaposi's sarcoma-derived
      cells. In vitro responses to alfa interferon.
AB  - We established long-term cultures from skin tumors of nine patients suffering
      from classical Kaposi's sarcoma (KS). Spindle cells obtained after enzymatic
      digestion were cultured on gelatin- or fibronectin-coated flasks in DMEM with 15%
      fetal calf serum, aFGF and heparin. Immunohistochemical staining was positive for
      MHC class I, laminin, type IV collagen, vimentin, alpha smooth muscle actin (20
      40% of cells), caldesmon (20%), calponin (20-40%) and smooth muscle myosin (20
      40%), and was negative for common leukocyte antigen, CD4, LFA1, CD34 and
      cytokeratin. Around 20% of cells up to the third passage in culture expressed the
      endothelial markers CD36, BMA 120 but were negative for UEA and Fc von
      Willebrand. Smooth muscle proteins were detected with immunoblotting. Using the
      polymerase chain reaction, human herpes virus 8 (HHV8) sequences were detected in
      primary cultures of three out of seven cell lines but were rapidly lost during in
      vitro passaging. KS-derived cells did not proliferate in serum-free medium, had a
      normal karyotype and did not grow in soft agar medium. Tumors formed in nude mice
      injected with KS-derived cells. The tumors were composed of mouse cells and were
      highly vascularized. Our results suggest that KS-derived cells are heterogeneous:
      the majority of cells have either a smooth muscle cell or a fibroblastic
      phenotype. Another minor cell compartment was composed of endothelium-derived
      cells. KS cells do not possess the characteristics of transformed cells in vitro
      and may be composed of polyclonal activated cells. Recombinant alpha interferon
      (rIFN) slightly inhibited the growth of KS-derived cells and increased the
      expression of MHC class I antigens. While cells were resistant to natural killer
      (NK) cell-mediated cytotoxicity, they became sensitive to rIFN-primed NK cells.
      Thus, the antitumor potential of rIFN against KS in vivo could result from
      immunomodulatory rather than from direct antiproliferative effects.

PMID- 9248623
TI  - Stimulation of collagen expression and glycosaminoglycan synthesis by midkine in
      human skin fibroblasts.
AB  - Midkine is a retinoid-inducible regulator of cell differentiation and cell growth
      in developing embryonic tissues. The effects of midkine on the expression of the
      extracellular matrix components, collagens and glycosaminoglycans, in dermal
      fibroblasts were studied. Midkine did not alter fibroblast proliferation.
      Collagen synthesis was stimulated in a dose- and exposure time-dependent manner
      and the maximum two-fold stimulation was achieved at a concentration of 100 ng/ml
      for 72 h treatment. Midkine increased the synthesis of type I and III collagens
      to the same extent. Glycosaminoglycan synthesis was also stimulated two-fold,
      mainly accounted for by an increase in hyaluronan synthesis. Midkine enhanced
      mRNA levels of alpha 1 (I), alpha 1 (III), alpha 1 (VI) collagens, transforming
      growth factor beta 1 and matrix metalloprotease-2 but did not alter the mRNA
      levels of elastin, MMP-1 and tissue inhibitor of metalloproteases-1. These
      results suggest that midkine is a potent stimulator of collagen and
      glycosaminoglycan synthesis and may prove useful in the therapy of delayed wound
      healing.

PMID- 9248624
TI  - Sulphation of the heterocyclic amine 1,2,3,4-tetrahydroisoquinoline in the human
      liver and intestinal mucosa: interindividual variability.
AB  - The sulphation rate of 1,2,3,4-tetrahydroisoquinoline (TIQ) was measured in the
      human liver and in the intestinal mucosa isolated from the transverse colon,
      ileum and duodenum. The rate (mean +/- SD) of hepatic TIQ sulphation was 500 +/-
      174 pmol/min per mg in women (n = 61) and 591 +/- 201 in men (n = 39; P =
      0.0087), varying over one order of magnitude in men and women. The sulphation
      rate of testosterone showed the same sex-dependent pattern and was correlated (r
      = 0.6055; P < 0.001) with that of TIQ. The frequency distribution of TIQ
      sulphation rate in human liver was bimodal: 70% of the population fell into the
      low-activity subgroup and the remaining 30% feel into the high-activity subgroup.
      In the colon (n = 56), the rate of TIQ sulphation was 30.4 +/- 15.6 pmol/min per
      mg and the values were similar in men and women (29.8 and 30.9 pmol/min per mg,
      respectively) but, varied over one order of magnitude and correlated (r = 0.7231;
      P < 0.001) with that of 4-nitrophenol. The rate of TIQ sulphation changed along
      the human bowel and mean (+/-SD) estimates for duodenum, ileum and transverse
      colon were 444 +/- 25, 182 +/- 87 and 30.4 +/- 15.6 pmol/ min per mg,
      respectively. The present results are consistent with the view that the
      heterocyclic amine TIQ is sulphated in the human liver and intestinal mucosa. TIQ
      sulphotransferase activity varies among subjects and is mostly associated with
      the liver and duodenum.

PMID- 9248626
TI  - Induction of cytochromes P450 1A, 2B and 2E in hamster tissues by acetone.
AB  - The inductive effects of acetone on cytochromes P450 1A, 2B and 2E in liver,
      kidney and lung were studied using hamsters administered acetone in drinking
      water. Acetone administration caused five-, two- and sixfold increases of the
      activities of aniline hydroxylase, ethoxyresorufin O-dealkylase and
      pentoxyresorufin O-dealkylase in liver microsomes; eight- and twofold increases
      of aniline hydroxylation and ethoxyresorufin O-dealkylation in kidney; and a
      twofold increase of aniline hydroxylation in lung, respectively. Immunoblot
      analyses of microsomal proteins using mouse monoclonal antibody 1-12-3 to rat
      P450 1A1 and rabbit antibody to human P450 2E1 revealed that acetone resulted in
      about three-, four- and twofold increases of proteins immunorelated to P450s 1A
      and 2E in hamster liver, kidney, and lung, respectively. Protein blot analysis
      using mouse monoclonal antibody 2-66-3 to rat P450 2B1 showed that acetone caused
      five- and twofold increases, respectively, of an immunoreactive protein in
      hamster liver and kidney but decreased the P450 2B protein by 48% in lung. RNA
      blot analyses using cDNA probes derived from mouse P450 1A1 and rat P450 2B1 cDNA
      clones demonstrated that acetone elicited two- and twelvefold increases of the
      mRNA levels of P450s 1A and 2B in hamster liver, respectively. Northern blot
      analyses using oligonucleotide probes derived from hamster P450 2E1 cDNA sequence
      detected two species of hybridizable mRNA in control liver. Acetone
      preferentially caused a threefold increase in the level of the larger-sized mRNA.
      Acetone produced little increase or no effect on mRNAs of cytochromes P450 1A, 2B
      and 2E in kidney and lung. The present study demonstrates that acetone induces
      the catalytic activity, protein and mRNA levels of P450s 1A, 2B and 2E in hamster
      liver, and causes various changes of the P450 levels in kidney and lung. Acetone
      induction of hamster P450s 1A, 2B and 2E might involve transcriptional and post
      transcriptional mechanisms.

PMID- 9248625
TI  - The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride
      induced abnormal liver function.
AB  - Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans.
      There are reports that exposure to VCM seems to induce abnormal liver function,
      liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In
      vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the
      electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde
      (CAA), which may either cause cell damage or be further metabolized and
      detoxified by glutathione S-transferases (GSTs). This study investigated whether
      or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST
      M1) correlated with abnormal liver function found in vinyl chloride exposed
      workers. For this study, 251 workers from five polyvinyl chloride plants were
      enrolled. The workers were classified into two exposure groups (high and low) and
      the degree of exposure was determined based on their job titles and airborne VCM
      concentration. The activity of serum alanine aminotransferase (ALT) was used as
      the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were
      determined by polymerase chain reaction and restriction fragment length
      polymorphism on peripheral white blood cell DNA. Other potential risk factors
      were also ascertained and the confounding effect was adjusted accordingly.
      Stratified analyses were used to explore the correlation between the alteration
      of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers
      exposed to different levels of VCM. The following results were obtained (1) at
      low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8
      (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT.
      (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR
      on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly
      associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3)
      Multiple linear and logistic regression also showed strong interactions of the
      VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations
      suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in
      the biotransformation of VCM, the effect of which leads to liver damage.

PMID- 9248627
TI  - Detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in white
      blood cells of workers occupationally exposed to styrene.
AB  - Styrene-7,8-oxide (SO), the major in vivo metabolite of styrene, is a genotoxic
      compound and a potential carcinogenic hazard to occupationally exposed workers.
      The aim of the present work was to investigate the ability of styrene exposure to
      induce formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in white blood cells
      (WBC) of boatbuilders occupationally exposed to styrene. The study of these
      adducts was conducted to see if styrene exposure can cause oxidative damage of
      DNA. The 8-OHdG/10(5) dG ratio from 17 styrene-exposed workers showed significant
      increases (mean +/- SD, 2.23 +/- 0.54, median 2.35, P < 0.001) in comparison to
      the controls (1.52 +/- 0.45, median 1.50). However, 11 out of 17 workers who were
      between the ages of 32 and 60 years and had been occupationally exposed to
      styrene for > 10 years showed higher 8-OHdG/10(5) dG ratios (2.31 +/- 0.62,
      median 2.37) in comparison to 6 workers with < 6 years of occupational styrene
      exposure (2.11 +/- 0.36, median 2.05; P > 0.05, no significant difference between
      the two groups of workers). The studies presented here provide an indication that
      styrene exposure can result in oxidative DNA damage.

PMID- 9248628
TI  - Using a four-compartment closed model to describe inhalation of vaporised ethanol
      on 1-14C-pyruvate kinetics in mice.
AB  - A four-compartment closed model was set up by means of a system of differential
      equations. A completely analytical solution of the four-compartment closed model
      was found by means of Laplace transform and Cramer's rule. 1-14C-pyruvate
      kinetics were studied in mice without and with inhalation of vaporised ethanol.
      The 1-14C-pyruvate kinetics were modelled by the four-compartment closed model,
      i.e. injected site, blood, 14CO2 expired in air, and 14C eliminated in urine. The
      kinetic parameters were estimated using the analytical solution of the four
      compartment closed model to fit expired 14CO2 and 14C eliminated in urine
      simultaneously. Although the results showed that the inhalation of vaporised
      ethanol increased the expired 14CO2, the compartmental analysis revealed that the
      increase of expired 14CO2 is mainly attributed to increased 1-14C-pyruvate
      transmembrane process. The developed model is useful for toxicokinetic analysis
      when blood is not easy to obtain. Moreover, the developed model can also be used
      to model two compartments as urine and faeces when the toxin is not eliminated
      through air.

PMID- 9248629
TI  - Thyroid peroxidase as toxicity target for dithiocarbamates.
AB  - In vivo ethylenebisdithiocarbamates and ETU are toxic to the thyroid gland. Since
      the molecular target of these compounds is thought to be thyroid peroxidase (TPO)
      which catalyzes the transfer of iodine to thyroglobulin, we examined the effect
      of these compounds on peroxidative activity in Chinese hamster ovary (CHO) cells
      transfected with the human TPO gene. The activity was inhibited by 50 microM ETU,
      5 microM ziram and 5 microM zineb, the last-mentioned effect being irreversible
      in the absence of iodide. Thiram had no effect. By contrast, the iodinating
      activity of TPO was blocked only by 5 microM ETU and 50 microM zineb but not by
      the other compounds. The effect on TPO-catalysed iodination could explain the
      differences in thyrotoxicity of these compounds in vivo.

PMID- 9248630
TI  - Effect of SKF-525A on liver metabolism and hepatotoxicity of tri- and dibutyltin
      compounds in mice.
AB  - The effect of pretreatment with SKF-525A, which inhibits hepatic cytochrome P450
      enzymes, on metabolism and hepatotoxicity was examined in mice orally
      administered tributyltin chloride (TBTC) or dibutyltin dichloride (DBTC) at a
      dose of 180 mumol/kg. Analysis of butyltin compounds showed that the main
      metabolites in liver of mice treated with TBTC alone were DBTC (40%) and
      dibutyl(3-carboxylpropyl)tin chloride (TCOOH; 12-26%), with the levels of other
      butyltin compounds including TBTC comprising < 12% of total butyltin compounds at
      3-24 h following treatment. The pretreatment with SKF-525A resulted in four- to
      tenfold increased TBTC levels and a significant decrease of debutylated
      metabolites, particularly DBTC (60 and 37% decrease) at both 3 and 6 h in liver
      of mice treated with TBTC, leading to complete inhibition of hepatotoxicity at 24
      h. At 24 h after TBTC treatment, hepatic levels of TBTC and most of the
      debutylated metabolites in mice pretreated with SKF-525A did not differ
      significantly when compared to those in unpretreated mice, resulting in the
      induction of hepatotoxicity at 48 h, although levels of TCOOH decreased even at
      24 h. In the case of DBTC treatment, > 95% of the butyltin compounds were
      detected as DBTC in liver, and the levels of DBTC inside cells as well as the
      induction of DBTC hepatotoxicity were unaffected by pretreatment with SKF-525A.
      These results suggest that debutylated metabolites, in particular DBTC, are the
      main metabolites of butyltin compounds responsible for the induction of
      hepatotoxicity following in vivo administration of TBTC. The results also
      indicate that cytochrome P450 enzymes may play a greater role in the metabolism
      of TBTC to form DBTC or butyltin trichloride (MBTC) than that of DBTC to form
      MBTC in liver of mice.

PMID- 9248631
TI  - The effects of lithium on neurulation stage mouse embryos.
AB  - The aim of this study was to evaluate the maternal toxicity and teratogenicity of
      lithium following intraperitoneal injection (i.p.) with lithium carbonate
      (Li2CO3) in pregnant CD-1 mice at the developmental stage of neurulation (E8; day
      of vaginal plug, E0). Light (LM) and electron (TEM) microscopic studies were also
      done to document the tissue and cellular changes occurring in embryonic tissues
      during the 48 h following treatment with 300 mg/kg body wt. Li2CO3. Controls were
      untreated or given equimolar amounts of NaCl or Na2CO3. A pharmacokinetic study
      showed that lithium was rapidly absorbed from the peritoneal cavity after the
      above-stated dose, achieved peak serum levels of 9.8 mmol/l within 1 h, had a
      half-life in the blood of 5 h and was completely cleared by 16 to 24 h after
      injection. Doses of Li2CO3 > 300 mg/kg body wt. were toxic to adult CD-1 mice.
      The latter dose had no detectable maternal toxicity but caused a 19% resorption
      rate and 2% incidence of open cranial neural tube defect in gestations terminated
      on E18. The malformation and resorption rates in gestations terminated on E11,
      E12 and E14 were not significantly different from those of E18. A strong litter
      effect was seen both for the resorption and malformation rates at all stages
      examined. At 3 h after treatment cell death became evident in the
      neuroepithelium. Cells continued to die for approximately 17 h and all necrotic
      debris had been cleared by 48 h. Also at 3 h after treatment small densely
      stained inclusions began to appear in mesodermal cells. TEM showed these to be
      non-membrane bound with an irregular shape and variable size; the lack of
      staining for acid phosphatase indicated a non-lysosomal structure; the
      ultrastructural features suggested a lipoid basis. At 24 h after treatment
      vascular ruptures and surface ectodermal ruptures were seen in the cranial
      mesoderm. These ruptures with extravascated blood were also seen at 48 h after
      treatment. A litter effect was also noted with respect to the tissue and cellular
      changes. These experiments suggest that the developing vascular system may be a
      target for lithium. In addition, the possibility is discussed that lithium
      induced cell death in the neuroepithelium may lead to neural tube defects.

PMID- 9248632
TI  - Modulation of energy status and cytotoxicity induced by FK506 and cyclosporin A
      in a renal epithelial cell line.
AB  - FK506 and cyclosporin A (CsA) are two potent immunosupressants with similar
      toxicity profile. Nephrotoxicity is the main adverse effect of both compounds.
      The aim of this study is to compare the in vitro nephrotoxic effects on renal
      epithelial cell line LLC-PK1 by measuring cell viability and energy status as
      evaluated by concentrations of ATP and ATP metabolites. Cell viability (expressed
      as IC50 was assessed via thiazolyl blue (MTT) assay after incubation for 4-24 h
      with FK506 or CsA. ATP and its metabolites were determined by HPLC after 4 and 6
      h incubation with FK506 or CsA alone at the respective IC50. Both FK506 and CsA
      decreased cell viability to similar extents, in a dose- and time-dependent
      manner. After 4 h incubation, both drugs decreased ATP levels (-25%) and
      increased uric acid levels. However, the latter percentage increase was twofold
      higher with CsA (18%) than with FK506 (9%). The energy charge, calculated
      according to levels of adenine nucleotides, was decreased by 10% in FK506-treated
      cells and by 27% in CsA-treated cells. At the end of 6-h incubation, FK506
      treated cells maintained ATP levels coupled with energy charge at near control
      levels whereas the levels were 32% lower in CsA treated cells. Compared to the 4
      h-incubation, the increase in uric acid was similar for FK506 but was doubled
      with CsA. The decrease in cell integrity and ATP depletion induced by CsA in LLC
      PK1 cells was only transiently observed with FK506. By preserving energy status,
      FK506 leads to fewer metabolic disturbances than CsA in the renal epithelial cell
      line LLC-PK1, demonstrating a minor potential nephrotoxicity.

PMID- 9248633
TI  - Biological durability and oxidative potential of a stonewool mineral fibre
      compared to crocidolite asbestos fibres.
AB  - Experiments are described concerning the differences in redox properties and
      biodurability of natural asbestos fibres and an experimental stonewool fibre
      incubated in Gamble solution and reconstructed surfactant fluid. Crocidolite
      exhibits a significantly higher oxidative potential compared to the tested
      stonewool fibres. The oxidative activity of both types of fibres is not constant
      during incubation over several weeks, but rather shows a sinoidal curve including
      reactivities much higher than those at the beginning of the incubation. A
      continuous loss of mass is concluded not to be definitively connected with a
      continuous loss of toxicity.

PMID- 9248634
TI  - A relationship between the generation of burn-associated type 2 T cells and their
      antagonistic cells in thermally injured mice.
AB  - Anti-type 2 T cells, generated in the spleens of thermally injured mice following
      the appearance of burn-associated CD8+, CD11b+, TCR gamma/delta + type 2 T cells
      (BA2T cells), have previously been shown to improve the resistance of thermally
      injured mice to Herpes virus infections. Anti-type 2 T cells, CD4+, CD28+, TCR
      alpha/beta +, IFN-gamma-producing T cell, are able to counteract the activity of
      BA2T cells which have been shown to be key cells in the increased susceptibility
      of thermally injured mice to these infections. In the present study, part of the
      generation mechanisms of anti-type 2T cells was examined in mice. Anti-type 2 T
      cells were detected in the spleens of unburned mice 3-7 days after i.v.
      inoculation (2 x 10(6) cells/mouse) of BA2T cells or a BA2T cell clone, defined
      as T6S cells. The suppressor cell activity of T6S cells was completely inhibited
      when they were co-cultured with anti-type 2 T cells from mice inoculated with T6S
      cells. Similar phenotypic and biological profiles of anti-type 2 T cells acquired
      from burned mice were expressed by T6S cell-induced anti-type 2 T cells. These
      results indicated that anti-type 2 cells may be generated in response to the
      appearance of BA2T cells in thermally injured mice. Immunoregulatory circuits may
      be involved in the generation of anti-type 2 T cells.

PMID- 9248635
TI  - Burn injuries, pain and distress: exploring the role of stress symptomatology.
AB  - Forty-three consecutive patients were assessed for post-traumatic stress 7 days
      after admission to hospital. Patients were asked to complete the Impact-of-Event
      Scale. Findings indicated that among the 43 patients 52.1 per cent experienced
      serious levels of stress symptomatology. A Visual Analog Thermometer was employed
      to measure the pain experienced at rest and during therapeutic procedures. High
      levels of post-traumatic stress were associated with higher pain scores during
      therapeutic procedures and more pain when at rest.

PMID- 9248636
TI  - The bigger the burn, the greater the stress.
AB  - Data characterizing the endocrine stress response to burn injury in children are
      sparse. We have measured the levels of the stress hormones arginine vasopressin,
      catecholamines-adrenaline, noradrenaline and dopamine-atrial natriuretic peptide
      and hormones of the renin-angiotensin-aldosterone system in admission blood
      samples taken from 35 children admitted to the burns unit of the regional
      children's hospital. Hormone levels were compared with the size of burn injury.
      With the exception of adrenaline, there were significant positive correlations
      between vasopressin (r = 0.707, p < 0.0001), plasma renin activity (r = 0.721, P
      < 0.0001), angiotensin II (r = 0.512, P = 0.002), aldosterone (r = 0.620, P <
      0.0001), noradrenaline (r = 0.430, P = 0.0189), dopamine (r = 0.627, P = 0.0024)
      and percentage burn surface area, and a negative correlation between atrial
      natriuretic peptide (r = 0.548, P = 0.0008) and burn surface area. It is
      concluded that the hormones which react to stress are very sensitive to burn
      injury in children, and that the magnitude of their response is closely related
      to the size of the burn surface area.

PMID- 9248637
TI  - Reduction of burn-induced gastric mucosal injury by an endothelin receptor
      antagonist in rats.
AB  - Burn-induced stress ulcers may be a major complication in critically burned
      patients. The pathophysiology of gastric mucosal ulceration is relatively
      unknown, however reduced gastric mucosal blood flow is one contributing factor.
      Endothelin (ET) is a well known vasoconstrictor peptide produced by vascular
      endothelial cells. Endothelin has been reported to have a fundamental role in the
      regulation of the systemic circulation. The plasma ET level is increased by burn
      injury, which also causes thrombosis and vessel occlusion. Endothelin has potent
      ulcerogenic and vasoconstrictor actions in the stomach where it induces gastric
      mucosal damage and increases gastric vascular tone. In the present study, we
      examined the effects of a new non-selective ET receptor antagonist, TAK-044, on
      burn-induced gastric mucosal injury in rats. Twenty male Sprague-Dawley rats
      weighting an average of 400 g were burned with hot water (90 degrees C) and then
      divided into two equal groups. The treatment group received 1 mg/kg of TAK-044
      via the dorsal vein of the penis immediately after burn trauma, while the control
      group received the same volume of saline. Gastric mucosal blood flow was measured
      with a laser Doppler flowmeter and the area of mucosal necrosis was also
      determined macroscopically and histologically. Inhibition of ET activity by TAK
      044 after burn injury significantly improved microvascular perfusion in the
      gastric mucosa and prevented the progression of mucosal damage in the stomach (P
      < 0.05). The present study supports the role of ET in burn-induced gastric
      ulceration (Curling's ulcer).

PMID- 9248638
TI  - Is there a need for antithrombin III substitution early after burn injury?
AB  - The changes in antithrombin III (AT-III) levels in the blood and restitution in
      coagulation parameters between patients receiving and not receiving AT-III
      substitution were examined early after burn injury. The study was divided into
      two parts with a total of 14 consecutive patients (per cent total body surface
      area (TBSA) > or = 20 per cent). The first six patients were given AT-III
      substitution when AT-III levels fell below 50 per cent. The second part examined
      the restitution of the coagulation parameters when the patients (n = 8) obtained
      AT-III substitution only at extremely low values of AT-III. The decline in AT-III
      observed occurred in parallel to the permeability changes and the haemodilution
      normally seen secondarily to the initial fluid rescucitation. The observed
      changes in the coagulation parameters were modest and no hepatic dysfunction was
      noted. In addition, no differences of the restitution in these coagulation
      parameters were noted between the substituted and non-substituted groups. These
      results suggest that changes in AT-III early after burn injury depend mainly on
      factors other than an ongoing disseminated coagulation process. Probable causes
      are increased capillary leak and haemodilution. Our results suggest that
      substitution of AT-III in the early postburn period, on the assumption that low
      levels alone indicate ongoing coagulation, is not warranted.

PMID- 9248639
TI  - The effect of burn blister fluid on fibroblast contraction.
AB  - Burns of the hand seem to be followed by more stiffness and contractures than
      other injuries. This study was aimed at examining whether burn exudate
      contributes to this difference. Five cell strains of human dermal fibroblasts
      were each treated with three samples of burn blister fluid and the effect
      compared with the rate of contraction of free floating fibroblast populated
      collagen lattices (FPCL). In addition, the response of fibroblasts from the
      dermis, fascia and peritendinous sheath of the hand to burn fluid were compared
      both in FPCLs and by the tensile forces they generated in the culture force
      monitor. Results of this study consistently show that the addition of burn fluid
      to culture medium stimulates fibroblasts to contract to a greater degree in the
      first 24-48 h. It is proposed that the presence of burn blister fluid provides
      materials which promote contraction. This in turn may contribute to the postburn
      stiffness seen clinically.

PMID- 9248640
TI  - The value of early enteral nutrition in the prophylaxis of stress ulceration in
      the severely burned patient.
AB  - A retrospective analysis of prospectively collected data was performed to compare
      the frequency of upper gastrointestinal bleeding (GIB) in seriously burned
      patients treated with either cimetidine and antacids or enteral nutrition for
      ulcer prophylaxis. Five hundred and twenty-six seriously burned patients admitted
      to the burn intensive care unit of the BG Trauma Centre Ludwigshafen during a 4
      year period were included into the study. All patients admitted to the burn unit
      from 1989 to 1991 received i.v. cimetidine (400 mg q4) for ulcer prophylaxis. If
      the intragastric pH dropped below 3.5, gastric pH was titrated with antacids up
      to > or = 4 via nasogastric tube. During the second 2-year period (1992-1993)
      early enteral nutrition alone was regarded to be ulcer protective and no further
      interventions for ulcer prophylaxis were routinely performed. Signs of overt
      upper GIB were monitored and documented through the entire study period. The
      overall occurrence rate of upper GIB in the cimetidine/antacids (C/A) group (n =
      253) was 8.3 per cent with six cases of serious bleeding in five patients (1.98
      per cent). In the enteral nutrition (EN) group (n = 273) the overall incidence of
      GIB was 3.3 per cent with two cases of serious bleeding (0.73 per cent). There
      were no deaths directly related to ulcer haemorrhage. The difference in the
      overall frequency of overt GIB between the groups studied was statistically
      significant (< 0.05). In our experience, early enteral nutrition is effective in
      the prevention of stress haemorrhage in the upper gastrointestinal tract.
      Additional medicinal prophylaxis is not required in burn patients.

PMID- 9248641
TI  - Burn injuries in the 1995 Hanshin-Awaji earthquake.
AB  - In the 1995 Hanshin-Awaji earthquake, 504 deaths were listed as fire related,
      although many of the victims may have been crushed or suffocated before they were
      burned. Census data related to surviving burn victims, however, were unknown.
      This study was designed to examine the medical requirements of those burn
      patients following the earthquake. Medical records of 2718 patients with injuries
      admitted to 95 hospitals during the 15 days after the earthquake were
      retrospectively reviewed. Only 44 patients (1.9 per cent) were hospitalized with
      burns. Scalds with less than 20 per cent total burn surface area (TBSA) were
      mainly observed; flame burns from earthquake-associated fires were rare.
      Morbidity rates increased in patients over 40 years old. Associated injuries were
      observed in 11 cases. These included three soft tissue injuries, one rib, three
      spine, three pelvis and two extremity fractures, and two cases of crush syndrome.
      Intensive care was required for only 10 patients, five of whom were transferred
      to hospitals that were undamaged or outside the earthquake zone. No relationship
      was noted between the number of burned houses and that of hospitalized burn
      patients. These results suggest that the number of burn patients requiring
      medical care was less than might have been expected in view of the total number
      of fire-related deaths in this urban earthquake.

PMID- 9248642
TI  - Epidemiology of burns in Malaga, Spain.
AB  - The incidence of burns in the province of Malaga, Spain, was determined by means
      of a descriptive, cross-sectional, population-based study, and the individual,
      social and environmental conditions of the patients were analysed. Five hundred
      families (1846 persons), selected by a three-stage, stratified sampling, were
      interviewed in their homes. Five hundred and six burns were found in 406 persons
      (1.25 burns/person); 89.5 per cent of these were in an urban environment and 10.5
      per cent in a rural environment. Eighteen and a half per cent of the sample had
      burnt themselves only once and 4.7 per cent more than once. The burns affected
      23.3 per cent of the population, although the majority were of little clinical
      importance. The risk of burns is greater in the urban environment than in the
      rural environment, with burns occurring most often in the home (65.8 per cent),
      and especially in the kitchen. The most frequent burns involve hot liquids with
      special risk from cooking oil. The other burns (in the strict sense of the word,
      proper burns or true burns), were primarily caused by contact. The incidence was
      higher in women (33.0 vs. 21.1 per cent), with burns occurring mostly on the
      hands. Only 21.9 per cent of the burns received the correct first aid after the
      accident.

PMID- 9248643
TI  - A retrospective study of etiopathological and preventive factors in a burns unit
      in Saudi Arabia.
AB  - A 10-bed state-of-the-art burns unit was commissioned at King Fahd Specialist
      Hospital, Buraidah, Al-Qassim and the first 90 cases admitted to the unit over an
      18-month period were analysed. The mean age (+/-SD) was 14.9 (+/-1.5) years with
      a range of 6 months-55 years. Fifty-one per cent were males, 52.2 per cent were
      children under 12 years of age and of these 85.1 per cent were under 5 years of
      age. Scalds and flames accounted for 90 per cent of the burns. Domestic burns
      formed the majority of cases, 64 (71 per cent), and most patients were admitted
      within the first 24 h (76 per cent). The mean (+/-SE) of the total body surface
      area (TBSA) was 23 per cent (+/-2.4) with a range of 3-98 per cent. The mean
      hospital stay for the whole group was 16.4 days. Overall mortality was five
      patients (5.6 per cent) while the mortality in critical burns was 14.3 per cent.
      TBSA was found to be the main factor influencing mortality. This study highlights
      the important factors that affect the outcome in this unit. Factors that can
      improve the morbidity and mortality rates in patients are highlighted. The study
      also reveals certain patterns and etiological factors in the Qassim region.
      Prevention by education through a national campaign remains the keystone in
      reducing the incidence of burns particularly in children and the maximization of
      resources.

PMID- 9248644
TI  - Hypernatremic suppression of neutrophils.
AB  - Phagocytic and bactericidal activities are important functions of the human
      polymorphonuclear leucocytes (PMNL) as the host defence against burn wound
      infection. The zone of stasis, just below the zone of coagulation, is a site of
      interaction between invading bacteria and PMNL. For many reasons the osmotic
      pressure at this site is elevated. In this study we evaluated the in vitro
      phagocytic and bactericidal activities of PMNL under hypernatremic conditions. At
      a sodium concentration of 180 mEq/l, phagocytic activity was suppressed. Although
      on average superoxide production was maintained within the normal range, it was
      suppressed in three of the ten cases studied. We conclude that the hypernatremic
      condition may weaken local defence against burn wound infection at the zone of
      stasis and may be a risk factor for burn wound sepsis.

PMID- 9248645
TI  - Return to employment after burn.
AB  - The increase in the survival rate of burned patients has stressed the need to
      study their rehabilitation. The purpose of our study was to characterize the
      factors influencing such patients' return to work. We conducted a mail survey
      among 316 patients aged 15-65 years, treated at Toolo Hospital Burns Unit between
      11 November 1988 and 31 December 1994. Of 175 participants, 130 (74 per cent)
      were men and 45 (26 per cent) women. The mean TBSA was 14.0 per cent, mean FT 6.4
      per cent and the mean time of hospital treatment (TOT) 17.5 days. Statistical
      significance was calculated by Mann-Whitney U test, Kruskall-Wallis one-way
      analysis of variance and Chi-square test as appropriate, with a probability level
      of 0.05. In the study, 54 per cent of patients whose burn area was 1-10 per cent,
      returned to work within 2 months. No difference was found between patients who
      had hand burns and those who had burn injuries in other parts of the body.
      Patients who did not return to work were significantly older (mean age 45 years)
      than those who did (mean ages varying from 33 to 36 years; P < 0.05). Total body
      surface area burned (TBSA), FT, TOT, age and employment status at the time of
      injury were the factors predicting the resumption of working ability after burn
      injury.

PMID- 9248646
TI  - Seven-year experience with a 'quarantine and isolation unit' for patients with
      burns. A retrospective analysis.
AB  - In the burns unit of the Red Cross Hospital, Beverwijk. The Netherlands we
      performed a retrospective analysis to evaluate whether the spread of multi
      resistant micro-organisms (MRMO) in burn victims with a high risk of
      contamination can be prevented by isolation in a quarantine and isolation unit
      (QIU). We analysed 1006 patients who where consecutively admitted to the burns
      unit between 26-03-1985 and 31-12-1992. The age TBSA, and the bacteriological
      status of all patients were recorded. With regard to the stay in the QIU we
      recorded the actual number of days between the accident and the time of
      admission, the duration of the stay, and the therapy given. Of 1006 patients, 72
      met the criteria of the Dutch Health Inspectorate for classification as high risk
      of MRMO contamination. Sixty-one of these 72 patients were treated in the QIU.
      The mean duration of stay in the QIU was 8.2 days, admission was at 10.2 days
      postburn, and 20 patients did harbour MRMO. There was no report of any cross
      contamination. Since the QIU became operational there have been no outbreaks of
      MRMO in our burns unit. In our opinion this shows the effectiveness of the QIU.

PMID- 9248647
TI  - Does tea tree oil have a place in the topical treatment of burns?
AB  - Burnaid is a sorbalene-based cream containing 40 mg/g of tea tree oil and 1 mg/g
      of triclosan. This investigation was carried out to determine the effect of
      Burnaid, a commercial tea tree oil preparation, against Enterococcus faecalis
      (ATCC29212), Staphylococcus aureus (ATCC29213), Escherichia coli (ATCC25922), and
      Pseudomonas aeruginosa (ATCC27853), with the activity of the base product in the
      commercial preparation. The organisms were suspended in sterile saline (0.5
      McFarland Standard) and inoculated onto horse blood agar (E. faecalis and S.
      aureus) or Mueller-Hinton agar (E. coli and P. aeruginosa). One hundred
      microliters of Burnaid unsterilized, Burnaid sterilized and the base product
      (Tinasolve) were placed in duplicate in wells cut into the agar plates. Sterility
      and inactivation cultures were also performed on the samples. None of the samples
      were found to be contaminated with bacteria prior to testing. Only S. aureus and
      E. coli showed zones of growth inhibition around the Burnaid and Tinasolve. Zones
      of growth inhibition (22 mm) were similar for the active product (Burnaid) and
      the base (Tinasolve). There was no activity against E. faecalis or P. aeruginosa.
      In view of our findings and literature indicating the cytotoxicity of tea tree
      oil against human fibroblasts and epithelial cells, it is recommended that this
      product should not be used on burn wounds.

PMID- 9248648
TI  - Inhalation injury treated with extracorporeal CO2 elimination.
AB  - A 38-year-old male was admitted to the intensive care unit with a full-thickness
      burn involving 30 per cent of his total body surface area (TBSA) and severe
      inhalation injury. Respiratory failure developed within 54 h and CO2 could not be
      eliminated, even by very invasive mechanical ventilation. Because of the
      patient's age and the minor extent of the burned TBSA, we started extracorporeal
      CO2 elimination (ECCO2-R) and continued ECCO2-R for 30 days, when the patient was
      weaned from ECC. The clinical course during ECCO2-R was complicated by major
      bleeding from a thoracotomy tube, from the site of tangential excision and by
      four septic episodes. Lung biopsy was performed twice on day 29 (during ECCO2-R)
      and day 58 (after ECCO2-R) after admission and revealed bronchiolitis obliterans
      without tendency to recovery. The patient died of sepsis with multiorgan failure
      on day 81 after trauma.

PMID- 9248649
TI  - Reconstruction of the eyelids and nose after a burn injury using a radial forearm
      flap.

PMID- 9248650
TI  - Breast cancer in previously burned skin: a postburn skin adnexal malignancy?
AB  - An unstable postburn scar at the submammarian fold 6.5 months after a burn injury
      turned out to be breast cancer. The unexpected histological findings and a
      possible correlation between the burn and the malignancy are discussed. This care
      report emphasizes the importance of histopathologic examination and the chance of
      unusual findings in a postburn ulcer.

PMID- 9248652
TI  - Recent references.

PMID- 9248651
TI  - Sparklers as a major hazard for burn injury.
AB  - Injuries caused by sparklers are a particular hazard for young children. Case
      reports highlight the potential severity of such injuries and recommendations are
      made with regard to prevention.

PMID- 9248653
TI  - Evaluation of the MUREX*ICE HIV-1.O.2 capture enzyme immunoassay for early
      identification of HIV-1 seroreverting infants in a developing country.
AB  - BACKGROUND: A simple, inexpensive serological assay is required for the early
      determination of HIV infection status among infants born to HIV-1-seropositive
      women in developing countries. OBJECTIVES: To evaluate the use of a commercially
      available capture enzyme immunoassay (EIA), the MUREX*ICE HIV-1.O.2, for the
      early identification of seroreverting, uninfected infants. STUDY DESIGN: Infants
      with a clearly defined HIV-1 infection status, as determined by polymerase chain
      reaction results and/or seroreactivity at 18 months, were tested for antibodies
      to HIV. The time to seroreversion using the capture EIA was compared with the
      results obtained using an indirect assay, the GENELAVIA MIXT EIA. RESULTS:
      Seroreverting infants were identified earlier with the capture than the indirect
      EIA; all of the uninfected infants were seronegative at 12 months with the
      capture EIA while 100% seroreversion was only seen at 18 months with the indirect
      EIA. CONCLUSIONS: In general, the capture EIA identified seroreverting infants 3
      6 months earlier than the indirect EIA. However, caution must be exercised in
      interpreting seroreactivity in a breast-fed population where HIV infection may
      occur in a child who has previously seroreverted.

PMID- 9248654
TI  - Differential serological diagnosis of HTLV-I and HTLV-II infection by external
      membrane protein peptide-based enzyme immunoassays.
AB  - BACKGROUND: HTLV antibody screening assays detect both antibodies to the
      etiological agent of adult T-cell leukemia and tropical spastic paraparesis HTLV
      I and to the less pathogenic HTLV-II. It is critical to make a differential
      diagnosis of the two viruses. OBJECTIVES: To design and evaluate synthetic core
      and envelope-derived peptide enzyme immunoassays (EIA) for serological
      differential diagnosis. STUDY DESIGN: Peptide EIAs were evaluated with a panel of
      202 plasma samples comprised of HTLV antibody positive, serologically classified
      as confirmed, indeterminate, or non confirmed, characterized as HTLV-I, HTLV-II
      or neither by genomic amplification. The peptide EIA with the best performance
      was further used to differentiate between HTLV-I and HTLV-II antibodies in 807
      samples from 18 countries in four continents and to provide ratios between the
      two infections. RESULTS: The gp46 peptide EIA correctly identified 96.5% of HTLV
      I and 98.6% of HTLV-II antibody-confirmed samples. HTLV-I was found exclusively
      in Japan and Caribbean countries; almost exclusively in Africa. HTLV-II
      represented 10-25% of samples from Canada, Chile and Venezuela and was
      predominant in the US. CONCLUSIONS: Differential diagnosis between HTLV-I and
      HTLV-II can be reliably performed using specific peptides from the gp46 envelope
      protein of each virus.

PMID- 9248655
TI  - Intrathecal IgM, IgA and IgG antibody response in tick-borne encephalitis. Long
      term follow-up related to clinical course and outcome.
AB  - BACKGROUND: Tick-borne encephalitis (TBE) of western subtype causes long-term
      morbidity and is considered a health problem in Scandinavia, eastern and central
      parts of Europe and Russia. The pathophysiology is not fully elucidated. As TBE
      RNA is rarely demonstrable in cerebrospinal fluid (CSF) the kinetics of the CSF
      antibody response to the disease has attracted attention. OBJECTIVES: To
      investigate the intrathecal TBE-specific antibody response and to correlate its
      intensity and persistence to the clinical course. To compare indirect,
      commercially-based ELISA methods indexed against albumin ratio or IgG ratio with
      the capture ELISA method for the establishment of CSF response. STUDY DESIGN: The
      specific IgM, IgG and IgA antibody responses in serum and CSF were analysed in 69
      Swedish patients included in a prospective study of TBE from the acute phase up
      to 11-13 months after onset. RESULTS: Antibody response by all three classes was
      demonstrable in serum and CSF. All methods were useful, but capture technique was
      the most sensitive and results were easiest to interpret. Peak IgM activity was
      seen early during the disease and persisted after 6 weeks. Maximum IgG levels
      were encountered in late convalescent samples (median 6 weeks). Intrathecal
      antibody production was demonstrable in nearly all patients: in 41% days 0-6, in
      97% days 7-19, in 98% days 21-61 and-at lower levels-in 84% of the patients after
      1 year (50/52 of CSF-serum sampled in the interval 11-61 days). Day 9 after
      onset, patients with dominating encephalitic symptoms showed significantly lower
      intrathecal IgM activity. The persistence of serum and CSF antibodies did not
      correlate to severity of disease. CONCLUSIONS: Capture IgM and IgG assays were
      superior to indirect ELISA. Low early CSF IgM response correlated to encephalitic
      symptoms, otherwise the intensity and duration of intrathecal antibody response
      were of limited value for the prediction of clinical course and long-term
      outcome.

PMID- 9248656
TI  - Detection of respiratory syncytial virus, parainfluenzavirus 3, adenovirus and
      rhinovirus sequences in respiratory tract of infants by polymerase chain reaction
      and hybridization.
AB  - BACKGROUND: Immunofluorescence assay (IFA) of viral antigens in nasal aspirates
      is largely used for the diagnosis of respiratory syncytial virus (RSV),
      parainfluenzavirus (PIV) type 3 and adenovirus (AdV) infections, whilst
      rhinovirus (RV) are detected by virus isolation technique (VIT) only. Using the
      two techniques, IFA and VIT, a significant number of specimens remain negative in
      spite of clinical and epidemiological presumptions of viral infection. OBJECTIVES
      AND STUDY DESIGN: The polymerase chain reaction (PCR) should improve the
      sensitivity of viral detection in clinical specimens. From October 1995 to March
      1996, 277 nasal aspirates from hospitalized infants were tested simultaneously by
      IFA, VIT, polymerase chain reaction and hybridization with a DNA enzyme
      immunoassay (PCR-EIA) for RSV, PIV-3, AdV and RV. RESULTS: RSV were detected in
      177 (64%) samples, PIV-3 in 23 (8%), RV in 40 (14%), and AdV in 30 (10%). PCR-EIA
      detected RSV in more samples 173 (62%) than IFA/VIT: 109 (39%) (P < 10(-7)). In
      most cases (79%), RSV-infected infants had lower respiratory tract disease, and
      routine and PCR techniques were positive. Out of the 23 PIV-3 infections, 12 were
      IFA/VIT- and PCR-EIA-positive, and 11 IFA/VIT-negative and PCR-EIA-positive. For
      RV, 35 (87%) specimens were PCR EIA-positive and 11 (27%) culture-positive; for
      AdV 30 samples were PCR-EIA-positive and four were culture-positive. Simultaneous
      viral infections were revealed in a significantly higher proportion than in
      conventional techniques: 18% (50/277) versus 2.5% (7/277); P < 10(-7). One RSV
      infection in four was associated with the presence of another virus, mainly PIV-3
      (16 cases) and AdV (13 cases). CONCLUSIONS: PCR-EIA detects more positive
      specimens than IFA/VIT, 1.5 times more for RSV, 1.9 for PIV-3, 4 for RV and 10
      for AdV, respectively. This increased sensitivity of viral detection by PCR-EIA
      compared to the IFA/VIT could suggest that samples containing low levels of virus
      are missed by routine methods IFA/VIT, and consequently, RSV or PIV-3, and above
      all RV or AdV are overlooked as agents of respiratory diseases. However, apart
      from the fact that the economic and convenient aspects of virus diagnostic cannot
      be missed, it is difficult to answer the following questions: what is the meaning
      of the detection of a viral sequences in nasal aspirates of infants, or may PCR
      have detected virus in patients who would not developed disease?

PMID- 9248657
TI  - Amantadine susceptibility in influenza A virus isolates: determination methods
      and lack of resistance in a Canadian sample, 1991-94.
AB  - BACKGROUND: Influenza A infections are an important cause of morbidity and
      mortality in the elderly and patients affected by chronic diseases or
      immunodeficiencies. Treatment and prevention of infection in hospitals and
      nursing homes often involve the use of amantadine, but resistant viruses may
      arise. OBJECTIVES: To assess the effectiveness of specific and sensitive methods
      for rapid screening and sequence confirmation of amantadine resistance, and the
      occurrence of amantadine resistance in recent influenza A virus isolates in
      Canada. STUDY DESIGN: A chicken antiserum-based enzyme linked immunoassay (ELISA)
      was developed and used to screen fifty influenza A isolates for amantadine
      resistance. Drug sensitivity was expressed as a percentage of virus growth
      inhibition. The efficiency of the assay was compared to that of a monoclonal
      antibody (mab)-based ELISA using influenza A strains from 1968 to 1994. Specific
      PCR primers, generated to amplify the M2 gene region where amantadine resistance
      mutations occur, were tested over a wide range of strains. Direct sequencing of
      the PCR fragments was performed to confirm the presence of resistance mutations.
      RESULTS: The polyclonal antiserum-based ELISA detected antigens from all recent
      H1N1 strains and H3N2 strains tested at an inoculum dilution ten-fold lower than
      the mab-based ELISA. Primers for the detection of amantadine resistance mutations
      consistently amplified a wide range of strains. The direct sequencing of the RT
      PCR amplicons generated, detected resistance mutations in reassortant and control
      viruses, the only strains found resistant by ELISA. All influenza A isolates
      (H3N2, H1N1) tested, except resistant controls and two reassortant viruses, were
      amantadine-sensitive as indicated by greater than 50% virus growth inhibition.
      CONCLUSIONS: Influenza A virus susceptibility to amantadine could be detected by
      using an antiserum-based ELISA, offering a simple and more sensitive alternative
      to the mab-based assay. Coupled with direct sequencing of the M2 gene, it
      provides a reliable way to detect and confirm resistance in influenza isolates.
      However, no resistant clinical isolates were detected in the sample.

PMID- 9248658
TI  - Evaluation of a non-isotopic polymerase chain reaction assay for detection in
      clinical specimens of herpes simplex virus type 2 DNA. Canadian Women's HIV Study
      Group.
AB  - BACKGROUND: PCR assays for detection of herpes simplex virus DNA sequences in
      clinical specimens are more sensitive than cell culture. OBJECTIVE: A non
      isotopic PCR assay (glycoprotein B HSV-2 assay, Roche Molecular Systems) for
      detection of HSV-2 DNA sequences was evaluated on 234 clinical specimens. STUDY
      DESIGN: A total of 125 patients (73 women, 40 men, 12 unknown) provided 162
      samples contained in viral transport medium. Samples were first inoculated in
      cell culture, centrifuged at 12,000 x g, lyzed and kept frozen. A total of 77
      women provided 42 cervicovaginal lavages and 30 vaginal tampons that were lyzed,
      tested with two isotopic HSV-2 PCR assays and kept frozen. All these samples were
      subsequently thawed and amplified with the glycoprotein B HSV-2 assay using
      generic primers for HSV glycoprotein B gene. Amplicons were captured on
      microplates with a HSV-2-specific probe and were detected with avidin-peroxidase
      and substrate. RESULTS: Of the 162 samples submitted to viral culture, HSV-2 was
      isolated from 73 while 89 did not contain HSV-2. All the 73 specimens with
      culture-proven HSV-2 infections tested positive with glycoprotein B HSV-2 assay
      (sensitivity of 100%). Herpesviruses other than HSV-2 were isolated from 34
      samples that were negative with glycoprotein B HSV-2 assay. Two culture-negative
      samples tested positive in the glycoprotein B HSV-2 assay (specificity of 98.7%).
      The latter samples could not be retested in confirmatory isotopic HSV-2 PCR
      tests. HSV-2 DNA sequences could also be detected directly in cervical lavages or
      vaginal tampons from 13 women with the glycoprotein B HSV-2 assay. CONCLUSION:
      Detection and typing of HSV-2 in clinical samples, including those collected in
      viral transport medium, can be accomplished with PCR assays using the AMPLICOR
      format.

PMID- 9248659
TI  - Quantitative detection of hepatitis C virus RNA in the serum of patients with
      chronic hepatitis C treated with interferon: a pilot study.
AB  - BACKGROUND: It is not known whether the measurement of serum hepatitis C virus
      (HCV) RNA by reverse transcription polymerase chain reaction (RT-PCR) could
      improve the management of patients with chronic hepatitis C being treated with
      interferon. OBJECTIVES: We analysed, in a pilot study, the relations between the
      variations of HCV-RNA and alanine aminotransferase (ALT) serum levels in 18 anti
      HCV positive patients treated with interferon. STUDY DESIGN: Serum HCV-RNA was
      measured, using a non competitive coamplification assay (Amplicor HCV Monitor),
      before (at 3, 2 and 1 months and baseline), during (first, third and sixth month)
      and after treatment for at least 8 months (range 8-17 months). HCV-RNA levels
      fluctuations were correlated with those of ALT and treatment outcome. According
      to the ALT pattern, four patients were non responders, seven partial responders,
      four relapsers and two long term responders. RESULTS: The median and mean
      baseline HCV-RNA levels were significantly different in patients infected by HCV
      type 1, 2 and 3, being 248,449, 235,506; 4170, 17,866 and 22,315, 79,273
      molecules per ml, respectively (P < 0.0001). We did not find any significant
      difference between median and mean baseline viremia of responders and non
      responders. After 1 month of treatment viremia was below the sensitivity levels
      of the assay in 77.7% (14/18) of the patients who normalized ALT, at least
      temporarily. On the contrary, HCV-RNA remained detectable in non responders.
      CONCLUSIONS: Our data suggest that HCV-RNA detection using Amplicor Monitor at
      the first month of treatment can be useful to identify non responders, avoiding
      three additional months of treatment as would be required by ALT monitoring
      alone. During the post-treatment follow-up, persistence of undetectable HCV-RNA
      and normal ALT levels helps to identify long term responders from patients with
      the risk of relapse in spite of biochemical remission.

PMID- 9248660
TI  - Comparative evaluation of three ELISA techniques and an indirect
      immunofluorescence assay for the serological diagnosis of Epstein-Barr virus
      infection.
AB  - BACKGROUND: The reference method for detecting specific Epstein-Barr virus (EBV)
      antibodies is indirect immunofluorescence (IF) with EBV-infected cells. The
      availability of protein purified from infected cells and more recently of
      recombinant polypeptides designed to contain immunodominant epitopes, has enabled
      the development of commercial enzyme-linked immunosorbent assays (ELISA) for the
      specific serodiagnosis of EBV infection. OBJECTIVE: Evaluation of ELISA-based EBV
      serodiagnosis in comparison with indirect immunofluorescence. STUDY DESIGN: We
      have first compared three commercial ELISA test systems with our in house
      indirect immunofluorescence assay for classifying correctly a set of serum
      samples into clinical categories (acute infection, past infection, interfering
      non-EBV infection, persistent infection). Additionally a prospective analysis
      with the best performing ELISA test (Enzygnost) was then carried out by running
      the ELISA test in parallel with the indirect immunofluorescence assay on 324
      consecutive clinical samples sent to our laboratory for EBV serodiagnosis.
      RESULTS: For the serodiagnosis of past EBV infection and acute EBV infection all
      three commercial ELISAs performed well in comparison with indirect
      immunofluorescence. When testing samples positive for cytomegalovirus (CMV),
      Toxoplasma or herpes simplex IgM, interference in the IgM tests was observed with
      the three ELISAs. In some instances we could demonstrate that the positive IgM
      results were due to EBV reactivation. The observed discrepancies between ELISA
      and IF for the serodiagnosis of chronic EBV infection or EBV reactivation, point
      to the difficulty for the serodiagnosis of persistent EBV infection on single
      serum samples. According to our prospective study the EBV IgG determination was
      accurate. A positive IgM result was not always indicative of an acute infection.
      Positive IgM results due to EBV reactivation were observed. A positive EBV
      nuclear antigen (EBNA) IgG result in those samples precluded acute infection.
      CONCLUSIONS: 90-95% of samples could be classified correctly into clinical
      categories by a two parameter ELISA system detecting IgG and IgM against a
      standardized mixture of EBV antigens, allowing standardization and automation of
      EBV-specific serology. The absence of EBNA IgG was useful as a second line
      confirmatory assay for acute EBV infection.

PMID- 9248661
TI  - Drug-mediated inactivation of cytochrome P450.
AB  - 1. Multiple forms of cytochrome P450 (CYP) catalyse the oxidation of chemicals of
      endogenous and exogenous origin, including drugs, carcinogens, steroids and
      eicosanoids. However, this unusual low substrate specificity also makes CYP
      susceptible to inhibition by a wide range of drugs, leading to pharmacokinetic
      interactions of potential clinical significance. 2. Some drugs are converted by
      CYP to reactive metabolites that bind covalently to sites within the active
      centre of the same CYP. Such mechanism-based inhibition leads to CYP inactivation
      or complexation. These processes give rise to long-term effects on drug
      pharmacokinetics, as the inactivated or complexed CYP must be replaced by newly
      synthesized CYP protein. 3. Drugs that inactivate CYP generally possess
      recognizable functional groups that are oxidized to reactive products. Thus,
      drugs with side chains containing unsaturated carbon-carbon bonds and furan ring
      systems are associated with CYP inactivation. Nitrogen-containing systems may
      also inactivate CYP. 4. Metabolites formed from drugs containing alkylamino and
      methylenedioxy functionalities can trap CYP as inert complexes without eliciting
      inactivation. However, the functional effects of inactivation and complexation on
      drug pharmacokinetics are indistinguishable. Drugs that elicit CYP complexation
      include the first generation macrolide antibiotics, but newer analogues appear
      much safer. Some antidepressants, antiepileptics and tuberculostatic agents have
      been associated with CYP complexation.

PMID- 9248662
TI  - Influence of muscle blood flow on fatigue during intermittent human hand-grip
      exercise and recovery.
AB  - 1. The influence of muscle blood flow on fatigue and recovery was studied in the
      forearm muscles of eight male subject performing a powerful isometric hand-grip
      exercise. The exercise was performed with the exercising forearm normally
      perfused and, on a separate occasion, with its blood flow occluded with a
      sphygmomanometer cuff. 2. In the no cuff condition, peak force declined to an
      initial plateau at 40-50% of the maximal voluntary grip force (MVC). When
      perfusion was occluded, the force decline was similar during the first minute of
      exercise, then force fell rapidly to exhaustion. 3. In a separate experiment to
      investigate the mechanisms underlying the plateau in force loss, occlusion of
      blood flow during the force plateau phase resulted in a rapid decline in force to
      exhaustion. 4. Recovery of peak force after the cuff exercise was significantly
      greater during the initial 3.5 min of recovery than after no-cuff exercise. After
      this time, recovery was similar for both conditions. 5. Muscle blood flow
      occlusion during intermittent exercise profoundly reduces endurance without
      prolonging recovery. Recovery time may depend on the duration and energy cost of
      the exercise rather than on the degree of force loss. 6. The present study
      suggests that the fall in muscle force induced by a continuous MVC is a
      combination of profound short-term fatigue in anaerobic muscle fibres due to the
      consumption of their short-term energy supplies, plus a decline in force
      production by aerobic muscle fibres that is the consequence of hypoxia. Thus, MVC
      may not be a good model of fatigue occurring under submaximal conditions, as
      hypoxia of type I fibres is unlikely to occur under physiological conditions in
      which muscle contractions are usually intermittent.

PMID- 9248663
TI  - Effects of adrenaline infusion on plasma lipids and noradrenaline levels in
      rabbits with adriamycin-induced cardiomyopathy.
AB  - 1. We investigated the acute effects of adrenaline infusion on plasma lipid
      levels in vehicle- and adriamycin-treated rabbits. Lipids were measured before
      and 30 and 60 min after the commencement of continuous intravenous administration
      of adrenaline (0.06 microgram/kg per min) or saline in pentobarbital
      anaesthetized rabbits. 2. Adrenaline infusion significantly increased plasma free
      fatty acid (P < 0.05) and noradrenaline (NA) levels (P < 0.05) in vehicle-treated
      control rabbits, but not in adriamycin-treated rabbits. However, adrenaline had
      no effect on plasma total cholesterol, free cholesterol, high-density lipoprotein
      cholesterol, triglyceride or phospholipid levels. 3. Pretreatment with
      propranolol almost completely inhibited increased plasma free fatty acid and NA
      levels associated with adrenaline infusion, suggesting that adrenaline increases
      plasma free fatty acid and NA levels via the stimulation of beta-adrenoceptors in
      vehicle-treated rabbits. 4. It is suggested that both the production of plasma
      free fatty acids and the release of NA via the activation of beta-adrenoceptors
      is reduced in rabbits with adriamycin-induced cardiomyopathy. This may be related
      to the down-regulation of beta-adrenoceptors caused by elevated plasma NA levels
      induced by cardiac failure.

PMID- 9248665
TI  - Effects of sarafotoxin S6c on renal haemodynamics and urine formation in
      anaesthetized dogs.
AB  - 1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor
      agonist, on renal haemodynamics and urine formation were examined in
      anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5
      ng/kg per min produced a transient increase in renal blood flow (RBF), with no
      change in systemic blood pressure and heart rate; RBF then decreased gradually to
      below the basal value. There were significant and dose-dependent increases in
      urine flow and free water clearance and decreases in urine osmolality during S6c
      infusion, whereas urinary excretion of sodium and glomerular filtration rate
      (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked
      increase in urinary excretion of nitric oxide (NO) metabolites, NO2- and NO3-
      (UNOxV). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and NG
      nitro-L-arginine (NOARG; 40 micrograms/kg per min), a NO synthase inhibitor, the
      renal vasodilator effect of S6c was abolished and marked reductions in RBF and
      GFR were observed. The S6c-induced diuretic action was not affected by NOARG. In
      the presence of NOARG, there was a small amount of UNOxV at the basal level and
      the administration of S6c did not increase UNOxV. 4. These results suggest that
      an intrarenal arterial infusion of S6c enhances the production of NO in the
      kidney and that this enhancement contributes to the peptide-induced renal
      vasodilation. In contrast, it is unlikely that S6c-induced water diuresis is
      related to NO production stimulated by this peptide.

PMID- 9248664
TI  - Alterations of cardiac alpha 1-adrenoceptor subtypes in hypothyroid rats.
AB  - 1. Alterations in the cardiac alpha 1-adrenoceptor and its subtypes in
      hypothyroid rats were studied by radioligand binding assays and reverse
      transcription-polymerase chain reaction (RT-PCR). Hypothyroidism was created by
      feeding rats with 0.2% 2-thiouracil solution instead of daily drinking water for
      20 days. 2. The density of cardiac alpha 1-adrenoceptors (Bmax) was increased
      from 67.5 +/- 4.3 fmol/mg in control rats to 81.1 +/- 7.2 fmol/mg (P < 0.05) in
      hypothyroid rats. 3. Compared with control rats, in hypothyroid rats the
      percentages of high-affinity sites for (+)-niguldipine and 5-methylurapidil were
      increased from 13.8 +/- 5.6 and 31.9 +/- 6.3%, respectively, to 24.9 +/- 7.3 and
      45.5 +/- 2.4%, respectively (both P < 0.05), while those for BMY7378 were
      decreased from 37.2 +/- 8.9 to 23.8 +/- 8.4% (P < 0.05), respectively. The
      percentage of high-affinity sites for WB4101 was not significantly different in
      control and hypothyroid rats (43.3 +/- 9.1 and 39.4 +/- 3.6%, respectively). 4.
      Reverse transcription-PCR experiments revealed that the steady state levels of
      mRNA for alpha 1A- and alpha 1B-adrenoceptors were increased, while those for
      alpha 1D-adrenoceptor were decreased in the hearts of hypothyroid rats. 5. The
      concentration-contraction response curves for noradrenaline in the presence of a
      beta-adrenoceptor antagonist in control and hypothyroid rats showed that the
      maximal response was reduced from 344 +/- 58 to 200 +/- 23 mg, respectively (P <
      0.05). 6. The data suggest that in hypothyroid rats the total number of cardiac
      alpha 1-adrenoceptors is increased. The change is subtype-selective, with levels
      of alpha 1A- and alpha 1B-adrenoceptors being increased and levels of alpha 1D
      adrenoceptors being reduced. Furthermore, the positive inotropic response
      mediated by alpha 1-adrenoceptors is reduced in hypothyroid rats.

PMID- 9248666
TI  - Competition of adenine nucleotides for a 1,3-[3H]-dipropyl-8-cyclopentylxanthine
      binding site in rat vas deferens.
AB  - 1. The binding of 1,3-[3H]-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a
      specific adenosine A1 receptor antagonist, was examined in rat vas deferens
      membrane preparations using radioligand binding techniques. 2. 1,3-[3H]-Dipropyl
      8-cyclopentylxanthine bound to these preparations with a KD of 1.07 +/- 0.14
      nmol/L (n = 6). The density of [3H]-DPCPX binding sites was 133.38 +/- 5.57
      fmol/mg protein. 3. Computer analysis indicated that nucleosides competed for
      [3H]-DPCPX binding at two distinct sites. The rank order of potency at the higher
      affinity site corresponded to R-phenylisopropyladenosine (R-PIA) > or = 2
      chloroadenosine (2-CIADO) > or = cyclopentyladenosine (CPA) > or = N
      ethylcarboxamidoadenosine (NECA) > s-phenylisopropyladenosine (s-PIA). Ki values
      were in the low nmol/L range. The rank order of nucleoside potency at the lower
      affinity site corresponded to R-PIA > or = CPA > or = NECA > or = 2-CIADO > S
      PIA. Ki values were in the low mumol/L range. 4. Nucleotides competed for [3H]
      DPCPX binding at a single site only. The rank order of potency at this site
      corresponded to alpha, beta-methylene ATP > or = beta, gamma-methylene ATP > or =
      ATP. Ki values were in the high mumol/L range. The site seemed to correspond with
      one of the two binding sites predicted by nucleoside competition binding. 5. The
      ATP-regenerating compound myokinase did not significantly change the competition
      curve for ATP, indicating that the competition for [3H]-DPCPX binding observed in
      the presence of ATP was due to an effect of ATP per se and not to an action of a
      degradation product. 6. The results demonstrate that in rat vasa deferentia there
      exist two distinct binding sites for [3H]-DPCPX. One of these sites binds only
      nucleosides and may represent an adenosine A1 receptor, as usually defined. The
      other site binds both nucleosides and nucleotides and may represent an atypical
      adenosine A1 receptor, an atypical P2 or a P3 purinoceptor.

PMID- 9248667
TI  - Components of the blood acid-base disturbance that accompanies urethane
      anaesthesia in rats during normothermia and hypothermia.
AB  - 1. We have studied the components of the metabolic acidosis that accompanies
      urethane anaesthesia in rats, both with and without the hypothermia that results
      from this anaesthesia. 2. Acid-base disturbances were analysed with an approach
      based on Stewart's analysis of acid-base chemistry. 3. The pH fall in the blood
      of normothermic anaesthetized rats (body temperature Tb) = 37 degrees C) was
      related to increases in plasma anions (lactate and [Cl-]), which decreased the
      strong ion difference ([SID]), as well as to increase the weak acid buffers due
      to increases in albumin. 4. A stronger metabolic acidosis was found in the blood
      of rats with hypothermia induced by urethane (Tb = 32 degrees C). Although plasma
      lactate was unchanged in hypothermic rats, [SID] decreased due to alterations in
      the plasma ionic balance. The metabolic acidosis found in hypothermia was also
      associated with increased weak acid buffers due to increases in albumin and
      inorganic phosphate. Further to hyperphosphataemia, signs of acute renal
      disfunction, such as increases in plasma [Mg2+] and blood urea nitrogen were
      found. Plasma retention of endogenous acids together with the retention of acid
      end-products of the metabolism of urethane because of acute renal failure may
      have contributed to strengthening the fall in pH and [HCO3-] found in urethane
      induced hypothermic rats.

PMID- 9248668
TI  - A low dose of streptozotocin prevents kainic acid-induced seizures and lethal
      effects in the rat.
AB  - 1. The effect of streptozotocin (STZ), a nitric oxide (NO) donor, on kainic acid
      (KA)-induced neurotoxicity was examined in Sprague-Dawley rats. 2. The
      administration of KA (8 mg/kg, i.p.) produced significant neurotoxicity
      accompanied with increased immunoreactivity for Fos-related antigen in the rat
      hippocampus. 3. Pretreatment with STZ (15 mg/kg, i.m.) significantly blocked the
      neurotoxicity induced by KA. 4. Thus, the neuroprotective effect of STZ may, at
      least in part, reflect the role of NO in inhibiting seizures.

PMID- 9248669
TI  - Long-term effect of manidipine on renal function and structure in
      uninephrectomized spontaneously hypertensive rats.
AB  - 1. Long-term effects of manidipine hydrochloride (MAN), a calcium channel
      blocker, were examined in three groups of spontaneously hypertensive rats (SHR).
      Group 1 was given uninephrectomy (UNX) and MAN treatment, group 2 was given UNX
      and was not treated with MAN and group 3 was given neither UNX nor MAN treatment.
      2. At week 15 after UNX, inulin clearance in group 1 rats decreased compared with
      rats in groups 2 and 3, but remained at the same level at week 40, when the level
      in group 2 rats declined below that in rats in groups 1 and 3. 3. Glomerular and
      tubulointerstitial lesions did not differ at week 15 after UNX among the three
      groups, whereas at week 40 both were advanced in the order of groups 2, 1 and 3.
      4. Proteinuria did not differ between rats in groups 1 and 2 over the
      experimental period. 5. At week 15, the kidney weights of group 1 rats were
      greater than those of group 2 rats, indicating more prominent tubular hypertrophy
      in the former group. This was confirmed by morphometry of the proximal tubuli. In
      contrast, the glomerular volumes of rats in groups 1 and 2 were enlarged compared
      with that of rats in group 3, with no difference between the former two groups.
      6. The findings suggest that MAN exerts renoprotective effects in SHR, both with
      regard to function and morphology. An effect on glomerular haemodynamics was
      considered to more likely be the mechanism underlying the renoprotective effect
      of MAN rather than that of a lowering of systemic blood pressure. 7. Augmented
      tubular hypertrophy after MAN treatment was an unexpected finding of the present
      study and the biological significance of this finding remains to be explored.

PMID- 9248670
TI  - The euglycaemic hyperinsulinaemic clamp: an evaluation of current methodology.
AB  - 1. The recognition of the role of insulin resistance in disease states and the
      recent development of new drugs that modify insulin-dependent metabolism has led
      to increased use of the euglycaemic hyperinsulinaemic clamp to measure in vivo
      insulin sensitivity, but several key aspects of the technique are poorly
      documented in the literature. 2. We have evaluated the reproducibility and
      intersubject variation of measurements of insulin sensitivity in groups of
      insulin-sensitive and insulin-resistant subjects and assessed the effects of hand
      warning on haemodynamic and metabolic responses. 3. Subjects participated in one
      of two protocols: (i) 18 healthy male volunteers and 18 patients with
      hypertension and glucose intolerance were clamped on two occasions, 1 week apart
      with measurements of insulin sensitivity (M) derived after 120 and 180 min of
      hyperinsulinaemia; and (ii) six healthy volunteers were clamped on one occasion
      with simultaneous sampling of antecubital and 'arterialized' (dorsal hand) venous
      blood for comparison of plasma glucose concentrations and oxygen saturation and a
      further six volunteers were clamped on two occasions with and without the use of
      hand warming. 4. Measurements of M derived after 120 min (M120) and 180 min
      (M180) of hyperinsulinaemia were reproducible: the coefficients of repeatability
      (mg/kg per min) of M120 and M180 were 1.0 and 0.9 for volunteers and 1.0 and 1.0
      for the patient group, respectively. The intersubject variation in insulin
      stimulus was high: coefficients of variation for M180 were 22% for volunteers
      compared with 38% for the patient group. In volunteers compared with the patient
      group, hand warming significantly increased venous oxygen saturations (95 +/- 2
      vs 79 +/- 18%, respectively) and glucose concentrations (5.2 +/- 0.2 vs 4.5 +/-
      0.4 mmol/L, respectively) and measurements of M were significantly higher using
      arterialized compared with antecubital venous blood. However, local hand warming
      was associated with systemic vasodilatation: blood pressure decreased (e.g. 6
      mmHg diastolic; P < 0.05) with a compensatory increase in heart rate (8 b.p.m.).
      5. In conclusion, clamps of 120 and 180 min duration yielded measurements of M
      that were reproducible. The technique is much more robust when used in the
      context of a crossover design because of the significant (20-40%) intersubject
      variation in M, even among apparently homogeneous male volunteers. Hand warming
      effectively arterializes venous blood and gives significantly higher M values,
      but induces systemic vasodilation, which may confound measurements of M.

PMID- 9248671
TI  - Cell-specific protein and gene expression in the juxtaglomerular apparatus.
AB  - 1. The juxtaglomerular apparatus (JGA) consists of a tubular component, the
      macula densa (MD), attached to a vascular component consisting of the afferent
      and efferent arterioles and the extraglomerular mesangium. The JGA is richly
      innervated by sympathetic fibres. 2. The MD is morphologically, histochemically
      and functionally different from the ascending thick portion of the loop of Henle
      where it is located. 3. The vascular component includes the vascular smooth
      muscle cells of the arteriole, the renin-producing cells or juxtaglomerular
      cells, extraglomerular mesangial cells (Goormaghtigh cells) and endothelial
      cells. They are coupled by gap junctions. 4. Physiological evidence indicates
      that the composition of tubular fluid at the MD regulates renin secretion and
      glomerular haemodynamics and that the JGA is important in the maintenance of body
      salt-water homeostasis. Evidence suggests that the MD exerts its action on the
      vascular component through a paracrine mechanism.

PMID- 9248672
TI  - Role of mesangial cells in macula densa to afferent arteriole information
      transfer.
AB  - 1. Extraglomerular mesangial cells are strategically positioned between the
      macula densa and the afferent arteriole. These cells form a syncytium and are
      connected with glomerular mesangial cells via gap junctions. The model of
      immunoablation of mesangial cells in anti-Thy-1 glomerulonephritis carries the
      promise for understanding the function of mesangial cells as potential
      transmitters of information between the macula densa and the afferent arteriole.
      2. The above anatomical relations between structures in the juxtaglomerular
      apparatus predict several possible routes of information flow. This review charts
      some hypothetical routes. 3. Research into the messenger systems involved in the
      transfer of signals from the macula densa to mesangial cells and from mesangial
      cells to the afferent arteriole suggests several candidate molecules to function
      in this capacity. Mechanisms of action for each candidate are discussed. 4. The
      oscillating nature of the afferent signal and efferent function in the
      tubuloglomerular feedback system, as well as other discoveries, offer a fertile
      field for future studies.

PMID- 9248673
TI  - Contractile properties of afferent and efferent arterioles.
AB  - 1. The balance of vascular tone of the afferent and efferent arteriole is a
      crucial determinant of glomerular haemodynamics. Despite their intimate
      anatomical relationship in the juxtaglomerular apparatus, the mechanisms that
      regulate afferent and efferent arteriolar tone are different. 2. In the afferent
      arteriole, two intrinsic mechanisms, the myogenic response and macula densa
      mediated tubuloglomerular feedback (TGF) play a dominant role, maintaining the
      glomerular filtration rate (GFR) at a constant level over a wide range of renal
      perfusion pressure. Studies have shown that these two mechanisms are modulated by
      nitric oxide (NO). In addition, an interaction between TGF and angiotensin II
      (AngII) seems to be essential to maintaining GFR despite large variations in
      daily intake of salt and water. 3. In the efferent arteriole, neither myogenic
      response nor TGF seems to be important, while AngII is one major factor involved
      in the control of vascular resistance. In addition, recent studies have provided
      evidence that NO and prostaglandins produced by the glomerulus may control
      resistance of the downstream efferent arteriole. 4. As the early segment of the
      efferent arteriole resides within the glomerulus, various autacoid hormones
      produced by the glomerulus may reach and directly act on this segment, thereby
      controlling the glomerular capillary pressure. Thus, it would be important to
      understand the differences in the mechanisms operating at the afferent and
      efferent arteriole, as well as their alterations in various physiological and
      pathological conditions.

PMID- 9248674
TI  - Membrane and secretory properties of renal juxtaglomerular granular cells.
AB  - 1. The control of renin secretion from renal juxtaglomerular granular cells on
      the cellular level is not yet completely understood. 2. There is evidence that
      calcium- and cyclic nucleotide-related pathways exert an opposite control of
      renin secretion. 3. There is accumulating evidence that the electrical properties
      of juxtaglomerular cells are important for the regulation of renin secretion.

PMID- 9248675
TI  - Characteristics of membrane transport processes of macula densa cells.
AB  - 1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and
      have their apical surface in contact with tubular fluid and their basilar region
      in contact with the glomerulus. These cells sense changes in luminal fluid sodium
      chloride concentration ([NaCl]) and transmit signals resulting in changes in
      vascular resistance (tubuloglomerular feedback) and renin release. 2. Current
      efforts have focused on understanding the cellular transport mechanisms of MD
      cells. Progress in this area has benefited from the use of the isolated perfused
      TAL-glomerular preparation, which permits direct access to MD cells. 3. Using
      microelectrodes to measure basolateral membrane potential (VBL) of MD cells, it
      was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As
      [NaCl] was elevated from 20 to 150 mmol/L, VBL was found to depolarize by over 30
      mV. 4. Basolateral membrane potential measurements were also used to identify an
      apical Na+:2Cl-:K+ cotransport pathway in MD cells that is the major pathway for
      NaCl entry into these cells. 5. Other work identified a basolateral chloride
      channel that is presumed to be responsible for changes in VBL during alterations
      in luminal [NaCl]. This channel, which is the predominant conductance across the
      basolateral membrane, may be regulated by intracellular Ca2+ and cAMP. 6. An
      apical Na+:H+ exchanger in MD cells was detected by measuring changes in
      intracellular pH using the fluorescent probe 2',7'-bis-(2-carboxyethyl)-5(and-6)
      carboxyfluorescein. 7. Using patch-clamp techniques, a high density of pH- and
      Ca(2+)-sensitive K+ channels was observed at the apical membrane of MD cells. 8.
      Other studies found that, at the normal physiological conditions prevailing at
      the end of the TAL (luminal [NaCl] of 20-60 mmol/L), reabsorption mediated by MD
      cells is very sensitive to changes in luminal [NaCl].

PMID- 9248676
TI  - Writing Amish culture into genes: biological reductionism in a study of manic
      depression.
AB  - Critical realism is used to explore the problem of reductionism in a classic (the
      Amish Study) and widely-cited study of manic depression. Along with related ideas
      drawn from the works of R.C. Lewontin, Arthur Kleinman, and Byron Good, it is
      shown that natural and social scientists deploy atomistic and holistic
      reductionism; this, in turn, leads to the construction of artificially 'closed
      systems' through the control of variables or exogenous forces. The psychiatric
      genetic studies of the Amish were predicated on the assumption that Amish society
      is homogeneous and unchanging and, therefore, closed. We conclude by arguing that
      interactions between behaviors and genes, where they exist, take place only
      within open systems, characterized by multiple mechanisms-social and biological
      that together co-determine any event. To move forward, it is argued, behavior and
      gene research requires recognition and resolution of the philosophical conundrums
      that accompany reductionism.

PMID- 9248677
TI  - The World War II plutonium experiments: contested stories and their lessons for
      medical research and informed consent.
AB  - During the Second World War medical researchers around the USA injected 18
      hospital patients with radioactive plutonium in order to learn its effects on the
      body. Two documents, a newspaper account and a university committee report, tell
      divergent stories of the scientists and patients involved in that experiment.
      This article uses those documents-plutonium narratives-as a catalyst for
      exploring the problematic representation of past human experimentation,
      assumptions of moral progress in medical research, and the nature of informed
      consent today. Informed consent is shown to be an evolving process and discursive
      practice that cannot be understood apart from its historical and cultural
      embeddedness.

PMID- 9248678
TI  - Problems related to alcohol use: a cross-cultural perspective.
AB  - The assessment, diagnosis, and classification of mental disorders are embedded in
      social and cultural norms. In view of their Anglo-Saxon origins, the prevailing
      diagnostic criteria and instruments for their assessment have a strong Western
      influence. Yet they are used internationally with the implied assumption of their
      cross-cultural applicability. The WHO Cross-Cultural Applicability Research (CAR)
      study was designed to test this assumption as it applies to disorders relating to
      the use of alcohol and drugs. This multi-disciplinary research project was
      conducted in nine countries having different patterns of alcohol and drug use.
      The results suggest that, even though some similarities exist with respect to the
      definition of problematic use of alcohol in these ethnically diverse societies,
      very substantial differences also exist. A number of core concepts underpinning
      diagnosis of disorders relating to the use of alcohol have no equivalence in the
      local languages of the various cultures, while some others lacked cultural
      applicability because of their relative 'distance' from cultural and ethnic norms
      of drinking. This distance often relates to the difficulties of adapting
      descriptors of drinking norms in a 'wet' culture to one that is decidedly 'dry'.

PMID- 9248681
TI  - Pericardial heart disease.

PMID- 9248679
TI  - Alternative psychotherapeutic practice among middle class Americans: II: Some
      conceptual and practical comparisons.
AB  - This article will contextualize ethnographic and clinical features that
      distinguish one particular alternative healing method (Self-Acceptance Training)
      from 'main-stream' psychotherapeutic procedures. Factors common to many
      psychotherapies are listed and a series of contrasts and comparisons made by
      examining definitions of: (1) presenting problems, (2) inciting events, (3)
      phasic development, (4) taxonomic classifications, (5) therapeutic interventions,
      and (6) prognostic formulations. The alternative method of treatment described in
      a companion publication ('SAT') is used to make some specific comparisons
      (Zatzick and Johnson 1997). Basch's (1980) concise recording of a dynamic therapy
      is borrowed for purposes of a comparative hypothetical treatment of his patient
      through a Self-Acceptance Training session. Some directions for future work are
      suggested.

PMID- 9248680
TI  - Neurasthenia, depression and somatoform disorder in a Chinese-Vietnamese woman
      migrant.

PMID- 9248682
TI  - The anatomy of the surgical operating microscope and operating positions.
AB  - This article explores the current status of magnification and illumination in
      endodontic surgery. The basic operations of the operating microscope are
      described in detail and common misconceptions regarding its operation are
      explained. Finally, the various operating positions used in endodontic
      microsurgery are described and illustrated.

PMID- 9248683
TI  - Conventional endodontics and the operating microscope.
AB  - Patients are increasingly wishing to undergo conventional endodontic treatment
      rather than to risk the loss of a tooth. Endodontic treatment in teeth that have
      been previously restored with extensive intracoronal or extracoronal restorations
      are often difficult to treat. The orientation of the root canals to the crown of
      the tooth may be lost, and this may often be compounded by the deposition of
      reparative dentin in the pulp chamber. The operating microscope allows better
      visualization of the working field, ensuring that the anatomy of the tooth is
      more readily inspected. This greatly enhances the clinician's ability to locate
      extra root canals and therefore increase the likelihood of a successful outcome.
      It should not be forgotten that the operating microscope also has a place in
      other fields of dentistry, especially restorative dentistry, and is an asset to
      both the specialist and the generalist.

PMID- 9248684
TI  - Micro-endodontic nonsurgical retreatment.
AB  - Clinicians frequently encounter endodontically treated teeth that are failing.
      The vast majority of these cases can be predictably retreated nonsurgically.
      Integration of specific technology, coupled with breakthrough techniques, are
      described and powerfully demonstrated. This article is designed for the dental
      team whose vision is to preserve strategic teeth and create endodontic excellence
      for its patients.

PMID- 9248686
TI  - Principles of endodontic microsurgery.
AB  - With bright illumination and magnification under the operating microscope, and
      addition of many microinstruments, endodontic surgery has become microsurgery.
      The microsurgical approaches allow the clinicians to perform endodontic surgery
      with smaller osteotomies, shallow bevels, preparation of isthmuses, examination
      of resected root surfaces, retropreparation in line with root canal, and precise
      placement of new filling materials. This article illustrates the advantages of
      microsurgery in endodontics.

PMID- 9248685
TI  - Microscopic management of procedural errors.
AB  - This article provides the clinician with several methods of dealing with
      furcation and post perforation as well as separated instruments. The endodontist
      must first understand how to eliminate procedural accidents that can occur, then,
      accurately and predictably treat those teeth to which accidents have occurred.
      Techniques to repair furcation and post perforations and retrieval of fractured
      root canal instruments are presented. An in-depth description of each technique
      has been included. Lastly, clinicians must be cognizant of limitations in
      treating these difficult problems that will arise in dental practice. Active
      patient participation and communication must be maintained during the scope of
      treatment to provide patients with the highest quality of endodontic service
      possible. A challenging variety of problems present to even the most skilled
      dental practitioner over time. The ability to diagnose and treat these difficult
      conditions relies heavily on the ability to envision adequately the source of the
      problem. In the past, operating loupes and headlamps were the most effective
      option afforded to practitioners as a solution to magnification and illumination.
      Not only were these devices cumbersome to use, but also the dentist was limited
      to performing the entire procedure under one level of magnification. The
      advantages of using the microscope in the correction of procedural errors
      enhances the operator's ability to perform each step in a procedure with a
      heightened sense of knowledge. The practitioner is cognizant of the exact details
      of an iatrogenic development because he or she has visualized the area in great
      detail. The reconstruction of the tooth or removal of instruments can be carried
      out with confidence because the dentist has more control of the working
      environment than ever before. New restorative materials and instruments are
      available so deliberate precision can be implemented with the microscope's
      ability to illuminate and magnify the working field. In time, these improvements
      in technology and techniques will result in greater confidence and success in the
      prevention and treatment of procedural errors.

PMID- 9248688
TI  - Soft tissue management in endodontic surgery.
AB  - This article provides an overview of the factors influencing the wound healing of
      oral soft tissues before, during, and after surgical endodontics. In more detail,
      the effects of flap design, handling of tissues, and wound closure are discussed.

PMID- 9248687
TI  - Hemostasis in endodontic microsurgery.
AB  - There are numerous ways to achieve hemostasis. With the abundance of hemostatic
      agents available and with the introduction of new products, one has to make an
      objective decision. A good agent achieves hemostasis within a short period of
      time, is easy to manipulate, is biocompatible, does not impair or retard healing,
      must be relatively inexpensive, is reliable, and works best for the particular
      surgical procedure. With these purposes in mind, the following sequence is
      recommended to achieve hemostasis during endodontic microsurgery. I. Presurgical:
      Give 2 to 3 Carpules of 1:50,000 epinephrine local anesthetic with multiple
      infiltration sites throughout the entire surgical field. II. Surgical: A. Remove
      all granulation tissue. B. Place an epinephrine pellet into the bony crypt
      followed by dry sterile cotton pellets. Apply pressure for 2 minutes. Remove all
      the cotton pellets except the first epinephrine pellet. Continue with the
      surgical procedure and remove the epinephrine pellet before final irrigation and
      closure. C. Alternatively, calcium sulfate can be mixed into a thick putty and
      packed against the bone cavity. Because it is a biodegradable material, calcium
      sulfate can be left in situ. In fact, in large bone defects and through-and
      through lesions, additional calcium sulfate can be placed to fill the entire bone
      cavity as a barrier material. Healing is more predictable with little chance of
      scar tissue formation. Calcium sulfate resorbs in 2 to 4 weeks. D. Small bleeding
      sites in the bone can be brushed with ferric sulfate solution. III. Postsurgical:
      Tissue compression before and after suturing cuts down on postsurgical bleeding
      and swelling. Hemostasis is imperative in endodontic microsurgery for better
      visualization, a good environment for placement of retrograde filling material,
      and a more efficient surgical procedure with less blood loss.

PMID- 9248689
TI  - The resected root surface. The issue of canal isthmuses.
AB  - Incomplete debridement of the canal isthmus is responsible for some surgical and
      nonsurgical endodontic failures. This article reviews the formation of canals
      isthmus and the new classification system. Recent research findings regarding the
      incidence of isthmus at different root end levels are included.

PMID- 9248690
TI  - Ultrasonic root end preparation.
AB  - Root end preparation techniques have historically been approached from the
      perspective of the restorative dentist. This article discusses how Black's
      principles for cavity design and preparation have been modified to reflect the
      advances in bonding chemistry.

PMID- 9248691
TI  - Is there a best retrograde filling material?
AB  - Operating microscopes and ultrasonic instruments have been used in root end
      filling procedures. The concepts, techniques, and materials for root end filling
      have been evolving. After eradicating or minimizing the irritants in the root
      canal system, the root end cavity has to be filled in a practical and convenient
      way. Super EBA seems to have more advantages. Some other potential root end
      filling materials and techniques are also discussed.

PMID- 9248692
TI  - Complications of sinus perforations and their management in endodontics.
AB  - The intimate position of the maxillary sinus to the apices of teeth creates
      problems if periapical inflammation occurs. This can lead to a perforation into
      the sinus and cause sinusitis. Persistent and complicated situations that do not
      respond after nonsurgical root canal treatment demand a suitable surgical
      therapy. Knowledge of the specific anatomic conditions, an adequate diagnosis,
      and an appropriate surgical procedure facilitate success rates that are
      comparable with those obtained in other regions, even in unfavorable initial
      conditions.

PMID- 9248693
TI  - Barrier membrane techniques in endodontic microsurgery.
AB  - The ultimate goal in endodontic microsurgery is the predictable regeneration of
      periapical tissues. One of the main concerns in treating an endodontically
      treated tooth which has a through-and-through osseous defect is that incomplete
      bone healing may be inevitable. This article reviews the use of different barrier
      membranes for bone regeneration. In addition, the indications, techniques, and
      prognosis of calcium sulfate in guided bone regeneration are presented.

PMID- 9248694
TI  - Intentional replantation.
AB  - A list of what was once advocated when performing a replantation versus what is
      done now follows: 1. It used to be advocated always to curettage the socket after
      removing the tooth. Now clinicians know not to touch the walls of the socket and
      only to aspirate gently the apical region if needed. 2. After removal, the tooth
      used to be held in gauze, desiccating viable PDL cells. Now the tooth is kept
      bathed in an emesis basin filled with HBSS, which maintains the viability of the
      PDL for 30 minutes. 3. All clinicians were able to do was visual inspection; now
      the microscope is used to illuminate and magnify the working area. 4. Splinting
      was done on every case; now clinicians rarely splint after replantation. 5.
      Narcotic pain medication was prescribed routinely; now clinicians premedicate
      with chlorhexidine rinse, anti-inflammatory medication, and sometimes
      antibiotics, rarely using narcotics. With increased understanding of the
      periodontium and improved techniques, replantation should no longer be viewed as
      a treatment of last resort, but rather a successful treatment alternative.

PMID- 9248695
TI  - The microscope. Its effect on your practice.
AB  - A number of different areas in which the microscope can help you and your
      practice have been covered. The bottom-line success depends on you and your
      commitment. If you make an honest, sincere effort, you will find yourself
      rejuvenated, and your practice will become more successful and endodontics more
      enjoyable.

PMID- 9248696
TI  - The insulin signalling system and the IRS proteins.
AB  - During the past few years, the insulin signalling system has emerged as a
      flexible network of interacting proteins. By utilizing the insulin receptor
      substrate (IRS)-proteins (IRS-1 and IRS-2), the insulin signal can be amplified
      or attenuated independently of insulin binding and tyrosine kinase activity,
      providing an extensible mechanism for signal transmission in multiple cellular
      backgrounds. By employing IRS-proteins to engage various signalling proteins, the
      insulin receptor avoids the stoichiometric constraints encountered by receptors
      which directly recruit SH2-proteins to their autophosphorylation sites. Finally,
      the shared use of IRS-proteins by multiple receptors is likely to reveal
      important connections between insulin and other hormones and cytokines which were
      previously unrecognized, or observed but unexplained.

PMID- 9248697
TI  - Control of PHAS-I phosphorylation in 3T3-L1 adipocytes: effects of inhibiting
      protein phosphatases and the p70S6K signalling pathway.
AB  - PHAS-I is a recently discovered regulator of translation initiation. Non
      phosphorylated PHAS-I binds and inhibits eukaryotic initiation factor-4E, the
      mRNA cap-binding protein that mediates a rate-limiting step in translation
      initiation. When PHAS-I is phosphorylated in response to insulin, the PHAS
      I/eukaryotic initiation factor-4E complex dissociates. The present study was
      conducted to investigate mechanisms involved in the control of PHAS-I.
      Phosphorylation of PHAS-I was monitored by immunoblotting after subjecting
      extracts to polyacrylamide gel electrophoresis in the presence of sodium dodecyl
      sulphate. This was possible because phosphorylation markedly decreases the
      electrophoretic mobility of PHAS-I. Incubating 3T3-L1 adipocytes with rapamycin
      and wortmannin inhibited insulin-stimulated phosphorylation of PHAS-I at
      concentrations similar to those that inhibited activation of p70S6K. Both agents
      increased the amount of PHAS-I that co-purified with eukaryotic initiation factor
      4E when extracts were fractionated using a cap affinity resin, indicating that
      PHAS-I binding to the initiation factor was increased. Incubating adipocytes with
      the protein phosphatase inhibitors, calyculin A and okadaic acid, increased PHAS
      I phosphorylation and opposed the effects of rapamycin on decreasing PHAS-I
      phosphorylation. However, neither okadaic acid nor calyculin A abolished the
      effects of rapamycin on PHAS-I. These results suggest that the phosphorylation of
      PHAS-I in response to insulin occurs via the p70S6K signalling pathway. By
      regulating eukaryotic initiation factor-4E, PHAS-I may have important roles in
      the control of both protein synthesis and mitogenesis.

PMID- 9248698
TI  - Mitogenic properties of insulin and insulin analogues mediated by the insulin
      receptor.
AB  - Insulin has traditionally been considered as a hormone essential for metabolic
      regulation, while the insulin-like growth factors (IGF-I and IGF-II) are
      postulated to be more specifically involved in growth regulation. The
      conventional wisdom is that they share each other's effects only at high
      concentrations, due to their weak affinity for the heterologous receptor. We
      discuss here the evidence that in the proper cellular context, insulin can be
      mitogenic at physiologic concentrations through its own receptor. We studied the
      insulin and IGF-I binding characteristics of a new model suitable for analysing
      insulin receptor mediated mitogenesis; that is, a T-cell lymphoma line that
      depends on insulin for growth, but is unresponsive to IGFs. The cells showed no
      specific binding of 125I-IGF-I and furthermore, no IGF-I receptor mRNA was
      detected by RNAse protection assay in the LB cells, in contrast with mouse brain
      and thymus. The cells bound at saturation about 3000 insulin molecules to
      receptors that had normal characteristics in terms of affinity, kinetics, pH
      dependence and negative co-operativity. A series of insulin analogues competed
      for 125I-insulin binding with relative potencies comparable to those observed in
      other insulin target cells. The full sequence of the insulin receptor cDNA was
      determined and found to be identical to the published sequence of the murine
      insulin receptor cDNA. The LB cell line is therefore an ideal model with which to
      investigate insulin mitogenic signalling without interference from the IGF-I
      receptor. Using this model, we have started approaching the molecular basis of
      insulin-induced mitogenesis, in particular the role of signalling kinetics in
      choosing between mitogenic and metabolic pathways.

PMID- 9248699
TI  - Signal transduction mechanisms in nutrient-induced insulin secretion.
AB  - The knowledge of the mechanism whereby glucose and other fuel stimuli promote the
      release of insulin by the pancreatic beta cell remains fragmentary. The closure
      of metabolically sensitive K+ channels and a rise in cytosolic free Ca2+ are key
      features of beta-cell metabolic signal transduction. However, these two
      signalling events do not account for the dose dependence of glucose-induced
      insulin secretion. In fact, recent evidence indicates that there are KATP channel
      and Ca2+ independent pathway(s) of beta-cell activation which remain to be
      defined. In this review, we have limited our attention to the recent developments
      in our understanding of the mode of action of nutrient secretagogues. A
      particular emphasis is placed in summarising the evidence in support of two new
      concepts: 1) oscillations in the glycolytic pathway and beta-cell metabolism
      contribute to the oscillatory nature of beta-cell ionic events and insulin
      secretion; 2) malonyl-CoA and long chain acyl-CoA esters may act as metabolic
      coupling factors in beta-cell signalling. Finally, we propose that the altered
      expression of genes encoding enzymes in the pathway of malonyl-CoA formation and
      fatty acid oxidation contributes to the beta-cell insensitivity to glucose in
      some patients with non-insulin-dependent diabetes mellitus.

PMID- 9248700
TI  - Engineered cell lines for insulin replacement in diabetes: current status and
      future prospects.
AB  - The recently completed diabetes complications and control trial has highlighted
      the need for improvement of insulin delivery systems for treatment of insulin
      dependent diabetes mellitus. Despite steady improvement in methods for islet and
      whole pancreas transplantation over the past three decades, the broad-scale
      applicability of these approaches remains uncertain due in part to the difficulty
      and expense associated with procurement of functional tissue. To address this
      concern, we and others have been using the tools of molecular biology to develop
      cell lines with regulated insulin secretion that might serve as a surrogate for
      primary islets or pancreas tissue in transplantation therapy. This article seeks
      to provide a brief summary of the current status of this growing field, with a
      particular emphasis on progress in producing cell lines with appropriate glucose
      stimulated insulin secretion.

PMID- 9248701
TI  - The new era of biotech insulin analogues.
AB  - Many of the structural properties of insulin have evolved in response to the
      requirements of biosynthesis, processing, transport and storage in the pancreatic
      beta cells, properties that are not necessary for the biological action of the
      hormone. It is therefore not surprising that wild-type insulin has far from
      optimal characteristics for replacement therapy. For example, native human
      insulin self-associates to hexameric units, which limits the possibilities for
      the absorption of the molecule by various routes. During the last decade new
      techniques of molecular design have emerged and recombinant DNA technology offers
      new and exciting opportunities for rational protein drug design. This review
      describes examples of recent advances in insulin engineering aimed at optimizing
      the hormone for therapy. Such approaches focus on improvements in the
      pharmacokinetic properties, storage stability, and feasibility for less intrusive
      routes of administration.

PMID- 9248702
TI  - Modifications in the B10 and B26-30 regions of the B chain of human insulin alter
      affinity for the human IGF-I receptor more than for the insulin receptor.
AB  - Inversion of the natural sequence of the B chain of human insulin (HI) from
      ProB28LysB29 to LysB28ProB29 generates an insulin analogue with reduced tendency
      to self-associate. Since this substitution increases the homology of insulin to
      insulin-like growth factor-I (IGF-I), we have examined the affinity of a series
      of insulin analogues with the general modified structure XaaB28ProB29 HI for
      binding to both human placental insulin and IGF-I receptors. The XaaB28ProB29 HI
      series is approximately equipotent to HI in binding to the insulin receptor with
      the exception of when Xaa = Phe, Trp, Leu, Ile, and Gly (40-60% relative to HI).
      Substitution with basic residues in the B28 position increased the relative
      affinity to the IGF-I receptor approximately 1.5-2-fold (ArgB28ProB29 >
      OrnB28ProB29 = LysB28ProB29). Substitution with acidic residues reduced relative
      affinity for the IGF-I receptor approximately 2-fold (CyaB28ProB29 = GluB28ProB29
      > AspB28ProB29). Combination of AspB10 substitution in conjunction with a
      modification in the B28-29 position (e.g. AspB10LysB28ProB29 HI) showed an
      additional 2-fold selective increase in affinity for the IGF-I receptor,
      suggesting that these two effects are additive. Addition of Arg residues at B31
      32, on the backbone of either HI or AspB10 HI, increased affinity for the IGF-I
      receptor 10 and 28 fold, respectively, compared to HI, confirming the
      significance of enhanced positive charge at the C-terminal end of the insulin B
      chain in increasing selectivity for the IGF-I receptor. This relative increase in
      IGF-I receptor affinity correlated largely, but not completely, with enhanced
      growth promoting activity in human mammary epithelial cells. In the case of
      LysB28ProB29 HI, growth activity correlated with dissociation kinetics from the
      insulin receptor which were shown to be identical with those of human insulin.

PMID- 9248703
TI  - Hypoglycaemia in diabetes mellitus--protecting the brain.
AB  - The human brain generally uses glucose as its principal metabolic fuel but
      cerebral metabolism and function during hypoglycaemia can be supported by a
      variety of substrates. Different brain regions may vary in this. The brain's
      ability to sense a falling blood glucose concentration and initiate a protective
      response varies according to prior glycaemic experience. The brain's ability to
      use non-glucose fuels may ultimately be of therapeutic use. Meanwhile, avoidance
      of even moderate hypoglycaemia during normal clinical treatment of diabetes
      mellitus leads to restoration of protective symptomatic responses to early
      hypoglycaemia, without necessarily causing a deterioration in overall glycaemic
      control.

PMID- 9248704
TI  - Alteration in brain glucose metabolism induced by hypoglycaemia in man.
AB  - Glucose is the usual fuel of brain tissue. As hypoglycaemia develops, a level of
      glycaemia is reached where glucose transport from the circulation is no longer
      sufficient to meet metabolic demands, and the brain signals for peripheral
      counter-regulatory responses and symptoms of hypoglycaemia ensue. The glycaemic
      threshold for these events can be shifted to lower glucose concentrations
      following a single episode of hypoglycaemia, and compensating central nervous
      system adaptations have been postulated in man. In nondiabetic subjects, rates of
      brain glucose uptake are initially impaired at a systemic glucose concentration
      of 3.6 mmol/l; whereas after 56 h of intermittent hypoglycaemia (3.0 mmol/l)
      brain uptake is preserved at normal rates even at 2.5 mmol/l. Increments in
      counter-regulatory hormones and symptoms are also triggered at lower glucose
      concentrations following recurrent hypoglycaemia. In 24 patients with insulin
      dependent diabetes stratified into three equal groups by HbA1c value, those in
      the lowest third of HbA1c range had rates of brain glucose uptake at 3.0 mmol/l
      that were equivalent to rates measured at 5.3 mmol/l. Patients in the other HbA1c
      groups had rates of brain glucose uptake during hypoglycaemia that were reduced
      by 30% relative to normoglycaemia-comparable to reductions seen in non-diabetic
      subjects. Thus, alterations in glucose uptake occur in the brain in order to
      maintain normal brain metabolism following experimental and clinical
      hypoglycaemia. Because of this enhanced glucose uptake, the brain has no need to
      signal for counter-regulatory responses and hypoglycaemia unawareness occurs.

PMID- 9248705
TI  - Microdialysis techniques in the study of brain and skeletal muscle.
AB  - Traditionally, plasma measurements have been used to monitor metabolic events and
      the actions of hormones that are actually taking place within tissue beds that
      are anatomically separated from the vascular compartment. It is generally assumed
      that the extracellular fluid (ECF) within metabolically active tissues is
      composed of substrates and hormones in concentrations that closely approximate
      those in plasma. Indeed, this view is implicit in non-steady-state tracer
      calculations. However, through the use of microdialysis techniques in the study
      of tissue metabolism this view is being challenged. Our data suggest that there
      may be substantial concentration gradients for a variety of fuels between plasma
      and ECF, i.e. fuels (e.g. glucose) removed from the circulation being lower and
      fuels (e.g. glycerol, lactate, some amino acids) produced by tissues being higher
      than plasma levels. In short, the metabolic milieu seen by individual tissues
      (and hormone receptors?) may, at least in some instances, be strikingly different
      from that in plasma, and as a result, plasma measurements by themselves may not
      appropriately define the contributions of specific tissues to metabolic events,
      and overlook the importance of metabolic processes which are largely restricted
      to individual tissue beds. Through the use of microdialysis as a means of
      directly sampling ECF from metabolically important body tissues and with the
      evolution of its use in animal and human research, this technique will continue
      to offer exciting new insights into tissue metabolism and to investigate
      fundamental issues that cannot be addressed by other methods.

PMID- 9248706
TI  - Intensive insulin therapy in clinical practice.
AB  - Achieving optimal blood glucose control, without an unacceptable rate of
      hypoglycaemia or unacceptable restrictions on lifestyle, is not simple with
      presently available insulin preparations and monitoring tools. There is
      considerable evidence that achieved control is relatively independent of the
      means or frequency of insulin delivery provided at least two injections per day
      are used, probably due to a combination of the unphysiological nature of insulin
      absorption profiles, the poor reproducibility of insulin absorption in any
      individual, and the erratic nature of normal human behavior. Accordingly the
      appropriate use of insulin to obtain good metabolic control requires the
      continued and informed expertise of both patient and advising professional, but
      also attention from both to self-motivation in order to make the desired
      lifestyle changes possible. Newer approaches to insulin delivery will continue to
      demand a high level of understanding and expertise to make them effective, until
      such time as automatic minute-to-minute control of insulin delivery can be
      restored.

PMID- 9248707
TI  - Translating the Diabetes Control and Complications Trial (DCCT) into clinical
      practice: overcoming the barriers.

PMID- 9248708
TI  - Are presently available insulin analogues clinically beneficial?
AB  - A number of insulin analogues have been developed by genetic engineering in order
      to improve the possibilities of substituting prandial and basal insulin
      requirements in diabetic patients by subcutaneous injection. For some short
      acting insulin analogues, in particular for [Lys(B28),Pro(B29)]-human insulin,
      preclinical and clinical trials have been performed. Despite the favourable
      pharmacokinetic and pharmacodynamic characteristics of these shortacting insulin
      analogues resulting in an attenuation of prandial hyperglycaemia following
      subcutaneous injection in diabetic patents, up to now, actual clinical benefits
      have not become apparent when they were used in clinical trials.

PMID- 9248709
TI  - Alternative insulin delivery systems: how demanding should the patient be?

PMID- 9248710
TI  - Advances and prospects in glucose assay technology.
AB  - The evolution of glucose assay methods has been central to the development of
      present therapies for diabetes mellitus. However, new blood glucose assay
      capabilities, such as convenient and truly continuous monitoring, are now needed
      to foster a new era of close blood glucose control. The principles and present
      status of glucose sensors being developed that may fill these requirements are
      reviewed here.

PMID- 9248711
TI  - The pathogenesis of atherosclerosis.

PMID- 9248712
TI  - Inflammation in the vascular wall as an early event in atherosclerosis.

PMID- 9248713
TI  - Endothelial control of vascular tone in diabetes mellitus.

PMID- 9248714
TI  - Cytosolic NADH/NAD+, free radicals, and vascular dysfunction in early diabetes
      mellitus.

PMID- 9248715
TI  - Factors regulating the expression of vascular permeability/vascular endothelial
      growth factor by human vascular tissues.

PMID- 9248716
TI  - Coronary heart disease and risk factors in NIDDM--experience from the United
      Kingdom Prospective Diabetes Study.

PMID- 9248717
TI  - Predictors of coronary heart disease and death in NIDDM: the Diabetes
      Intervention Study experience.

PMID- 9248718
TI  - Influence of diabetes mellitus on the heart and macrovascular mortality.

PMID- 9248719
TI  - Heart abnormalities in IDDM.

PMID- 9248720
TI  - Microvascular heart disease in diabetes mellitus.

PMID- 9248721
TI  - Antihypertensive treatment and mortality in diabetic patients. What is the
      evidence?

PMID- 9248723
TI  - Insulin resistance due to hyperglycaemia: an adaptation protecting insulin
      sensitive tissues.

PMID- 9248722
TI  - Impaired glucose tolerance--is it relevant for cardiovascular disease?
AB  - Although IGT is clearly associated with increased cardiovascular risk factors,
      there is currently conflicting data regarding the association of IGT with
      cardiovascular disease. This is true particularly for stronger study designs,
      namely prospective studies. This is partly because of the relatively few studies
      instituted since the WHO IGT criteria were developed [1] but also because there
      may be uncertainty about whether other risk factors such as blood pressure or
      dyslipidaemia should be controlled for. If one believes that IGT (that is mildly
      elevated glucose levels) is responsible for increased cardiovascular risk
      factors, then multivariate adjustment should not be done. Furthermore, the high
      variability of the oral glucose tolerance test needs to be taken into account.
      Lastly, if IGT is a risk factor for CHD, it is not clear that the increased risk
      of CHD is restricted solely to those IGT subjects who convert to NIDDM.

PMID- 9248724
TI  - Is insulin vasculotoxic?

PMID- 9248725
TI  - Diabetes mellitus, dyslipoproteinaemias and atherosclerosis.

PMID- 9248726
TI  - LDL heterogeneity: implications for atherogenicity in insulin resistance and
      NIDDM.

PMID- 9248727
TI  - The pathogenetic role of impaired fatty acid trapping by adipocytes in generating
      the pleiotropic features of hyperapoB.

PMID- 9248728
TI  - Molecular basis and promise of genetic therapy for diabetic dyslipidaemia:
      studies in an animal model of diabetes.

PMID- 9248729
TI  - Pharmacological reversal of advanced glycation end-product-mediated protein
      crosslinking.

PMID- 9248730
TI  - Cardiovascular effects of sulphonylurea derivatives.

PMID- 9248731
TI  - A new method for in vivo evaluation of biofilms on surface-modified silicone
      rubber voice prostheses.
AB  - A new method is presented that permits a rapid and accurate in vivo evaluation of
      biofilm formation on surface-modified silicone rubber voice prostheses. The
      method is based on partial modification of a Groningen button voice prosthesis by
      exposing half of the prosthesis to an argon plasma. This results in one side of
      the prosthesis becoming hydrophilic while leaving the unmodified side hydrophobic
      as a control. Modified prostheses were placed in patients for an evaluation
      period of approximately 4 weeks. Despite making the silicone rubber surface
      hydrophilic, biofilm formation was stimulated when compared to unmodified,
      hydrophobic silicone rubber. Findings show that biofilm formation on voice
      prostheses is influenced by hydrophobicity of a silicone rubber surface. The
      method of partial surface modification used was seen to be suitable for
      demonstrating such influences regardless of nutrition and other variations in the
      patient's lifestyle. Microbiological analysis of the biofilms on both sides of
      the prosthesis valve did not show any changes in microbial composition, with
      Candida albicans, streptococci and staphylococci being the most commonly isolated
      strains.

PMID- 9248732
TI  - The anatomy of the human promontory for laser Doppler flowmetry.
AB  - Studies of the dynamic characteristics of cochlear blood flow (CBF) utilizing
      laser Doppler flowmetry (LDF) in laboratory animals have provided a new approach
      to the understanding of control mechanisms of CBF and the role of the CBF in
      cochlear disorders. However, few studies exist indicating that LDF of human CBF
      may be possible. Since bone thickness, density, structure characteristics, and
      blood flow all greatly affect LDF recording, we examined the anatomy of the human
      promontory for inter-individual variations in thickness, quality and vascularity
      of the bone and mucosa and recorded middle ear topographic relationships to the
      underlying cochlear lateral wall vasculature. Temporal bones from 21 cadavers
      without known premortem histories of ear disease were obtained. India ink was
      infused selectively via the vertebral or carotid system to study the origin of
      bone/ mucosa circulation to the otic capsule. Light microscopy revealed that the
      human promontory was characterized as cortical bone having few blood vessels. The
      thickness of the bone measured at four horizontal levels and mucosa at the top of
      promontory and anteriorly around the tympanic plexus varied from 1.67 +/- 0.64 to
      1.13 +/- 0.26 mm for bone and 0.06-0.13 mm for mucosa. The thinnest bone was
      found around the tympanic plexus, where the bone thickness varied from 0.6 to 1.2
      mm. Previous data indicate that current LDF instruments can provide a linear
      measure of blood flow through bone thicknesses of 1-3 mm or more (depending on
      the type of bone). Data from the current study indicate that direct valid dynamic
      measures of CBF are possible in humans. Since the optimal area available is
      small, the topography of the middle ear should be well known and the recording
      site well defined to obtain valid results.

PMID- 9248733
TI  - Pure-tone audiometric and impedance measurements in school-aged children in
      Finland.
AB  - Pure-tone audiometric and impedance examinations were performed in 687 Finnish
      school children in the first, fourth and eighth grades (ages, 7, 10 and 14 years
      old) to study the sensitivity and usability of hearing and tympanometric
      screening examinations in schools. There were 138 children (20.1%) with a hearing
      loss > 15 dB in at least one frequency. Among these children, 103 were found to
      have pure sensorineural losses while 35 children had conductive losses. Of all
      the sensorineural losses, 118 of the cases involved slight high-frequency
      changes. Six children had hearing losses at speech range and all had been
      previously diagnosed. Six other children had 20-30 dB losses at 3-6 kHz, with 5
      of these children diagnosed for the first time. Twenty-four of the children with
      conductive losses had middle ear effusions that were found at a 15 dB screening
      level for hearing. When the limit of normal tympanometric peak pressure was-150
      daPa, 36 of 38 ears with middle ear effusions were found tympanometrically.
      Judging by the findings of the present study, we recommend that routine pure-tone
      audiometric screening for 7- and 10-year-old children in schools could be
      discontinued but should be continued for 14-year-old children. In contrast,
      tympanometry with a tympanometric peak pressure limit at-150 daPa should be used
      as a screening procedure for 7-year-old children on school entry.

PMID- 9248734
TI  - Correction of saddle nose deformities by coral implantation.
AB  - The coral or Madrepororia is a sea invertebrate with a skeleton morphologically
      and chemically very similar to mineral bone. In 1990 we implanted coral blocks,
      sterilized by gamma irradiation, into the nasal dorsa of ten dogs. Resorption and
      substitution with bone or fibrous tissue were observed within 6 months. Between
      1991 and 1994 biocoral was used in 20 patients with saddle nose deformities in
      order to augment the nasal pyramid and dome. Two extrusions were observed in the
      early postoperative period during follow-up. One of these extrusions was related
      to trauma and necessitated removal of the implant. Our findings show that coral
      is a suitable alloplastic material that can be used in the correction of saddle
      nose deformities.

PMID- 9248735
TI  - The concentration of u-PA and PAI-1 antigen in tissue extracts of nasopharyngeal
      carcinoma.
AB  - We measured the antigen levels of urokinase-type plasminogen activator (u-PA) and
      plasminogen activator inhibitor-1 (PAI-1) in tissue extracts from nasopharyngeal
      carcinomas. An increase in u-PA antigen was observed with the advanced stages of
      disease. However, the levels of PAI-1 antigen decreased with each advanced stage.
      These results suggest that local administration of antiplasminic agents may be
      effective in suppressing tumor invasion.

PMID- 9248736
TI  - The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after
      cisplatin treatment in guinea pigs.
AB  - The effect of sodium thiosulfate (STS) on the pharmacokinetics and ototoxicity of
      cisplatin (CDDP) was investigated in guinea pigs. Animals received three
      intramuscular injections of 7.5 mg/kg CDDP separated by intervals of 5 days with
      or without STS (1,000 mg/kg) administered intraperitoneally immediately and 1 h
      after each injection of CDDP or 3 and 6 h later. When administered alone, CDDP
      caused total outer hair cell (OHC) loss in the basal and second turns of the
      cochlea. In the group administered CDDP and STS, damage to the OHCs was mild when
      STS was given concurrently, but was severe when STS was given 3 and 6 h later.
      Pharmacokinetics measured as free and total platinum (Pt) concentrations in
      plasma and total Pt concentration in perilymph was not affected after
      administration of STS with CDDP. These results suggest that an inactive Pt
      thiosulfate complex is formed in plasma and is measured as a free Pt component
      which enters the perilymph via the blood-cochlear barrier. Two possible
      mechanisms are proposed by which STS reduces ototoxicity: entry of CDDP into
      target cells such as OHCs and strial marginal cells or binding to intracellular
      macromolecules of these cells is prevented.

PMID- 9248737
TI  - Existence of voltage-dependent Ca2+ channels in vestibular dark cells:
      cytochemical and whole-cell patch-clamp studies.
AB  - To determine whether functional Ca2+ channels are present in vestibular dark
      cells, changes in intracellular Ca2+ concentration ([Ca2+]i) due to K+
      applications were measured using the Ca(2+)-sensitive dye (fura-2) and patchclamp
      whole-cell recordings were made in dark cells isolated from the ampullae of the
      semicircular canal of the guinea pig. Exchange of the external solution with a
      buffer medium containing a high K+ concentration (80 mM K+ or 150 mM K+) caused a
      concentration-dependent increase in [Ca2+]i in vestibular dark cells. Application
      of 1 microM nifedipine as a Ca2+ channel antagonist completely blocked the
      increase in [Ca2+]i. Further treatment with 10 microM BAY K 8644 as a Ca2+
      channel agonist caused an increase in [Ca2+]i. In the patch-clamp whole-cell
      recordings a 1-s depolarizing pulse given into the dark cell in the presence of a
      high barium concentration (50 mM Ba2+) induced an inward current. In determining
      the current-voltage relationship, a current was detected at a potential that
      depolarized at-50 mV and was maximal at +10 mV. This inward current was
      completely blocked by 1 mM La3+ as a Ca2+ channel antagonist. These findings
      suggest the presence of voltage-dependent Ca2+ channels in dark cells, which have
      a presumed function in the regulation of [Ca2+]i in the vestibular endolymph.

PMID- 9248738
TI  - Activity of the subglottic voice ("chest resonator"): an echo-tomographic and
      acoustic study.
AB  - In contrast to numerous studies of the activity of the supraglottic voice
      resonator and its acoustic effect, little is known about the subglottic resonator
      and its function. In the present investigation the phonatory behavior of the
      lower airway (the "chest resonator") was studied and the quality of its acoustic
      output analyzed. Echo-tomographic analysis was used to study the tracheal
      diameter during various phonatory tasks. Acoustic analysis was also used, based
      on acoustic separation between the supra- and subglottic airways (including
      perceptual testing, sound pressure levels, and long-time spectral analysis).
      Evidence is presented of chest resonator activity having both perceptual and
      spectral effects.

PMID- 9248739
TI  - Giant cell tumor of the temporal bone (osteoclastoma).
AB  - A 49-year-old white female patient was referred to the ENT Department,
      Zentralkrankenhaus, Bremen, because of conductive hearing loss. Widespread tumor
      formation was found in the left temporal bone and was identified by biopsy to be
      an osteoclastoma. The tumor was extirpated surgically and reconstruction was
      performed. Periodic clinical follow-ups during a 36-month period after surgery
      have included control computed tomographic scans and have shown no evidence for
      recurrent disease. The specific pathology of the osteoclastoma is presented and
      different ways for treatment are discussed.

PMID- 9248740
TI  - Multiple neurinomas of the parapharyngeal space.
AB  - The authors describe a rare case of three neurinomas arising in the
      parapharyngeal space. In spite of the large extension of the neoplasms, the only
      symptom reported by the patient was some dysphagia. Magnetic resonance imaging
      allowed us to identify the three masses and suppose their diagnosis. The
      therapeutic approach used is also reported.

PMID- 9248741
TI  - Pharyngolaryngectomy with total esophagectomy following concomitant
      chemoradiotherapy for advanced and/or salvage cases of hypopharyngeal carcinomas.

PMID- 9248742
TI  - Adverse effects of highdose vitamin A during radiotherapy.

PMID- 9248743
TI  - Septic shock as a predictor of mortality in bacteremia caused by coagulase
      negative staphylococci.
AB  - Fifty episodes of bacteremia caused by coagulase-negative staphylococci at
      Hacettepe University Hospital over a five-year period were reviewed to evaluate
      the factors influencing the prognosis. Overall mortality and mortality due to
      bacteremia were 36% and 24%, respectively. Septic shock was determined to be the
      only factor adversely influencing mortality in both univariate and multivariate
      analyses. Age, sex, duration of hospitalization, origin of infection, underlying
      disease, presence of central intravascular or urinary catheters, and prior
      antibiotic therapy were not statistically significant parameters in predicting
      septic shock.

PMID- 9248744
TI  - Chorioamnionitis caused by gram-negative bacteria as an etiologic factor in
      preterm birth.
AB  - The role and microbiological causes of infection and inflammation of the
      chorioamnion were studied in 85 patients with spontaneous preterm deliveries (<
      37 weeks) and in 85 control patients with full term deliveries. Microorganisms
      were isolated from the freshly separated chorioamnion in 55% of preterm and 26%
      of term deliveries (p < 0.001). Isolation rates of gram-negative enteric bacteria
      were significantly higher in preterm deliveries than in term deliveries (p <
      0.001), whereas differences in the isolation of other bacterial species were not
      significant. Histological chorioamnionitis was noted in 49% of preterm and 14% of
      term deliveries (p < 0.001), and was strongly associated with a positive
      chorioamniotic culture in both groups (p < 0.001). Histological chorioamnionitis
      was noted in 94%, 54%, and 4% of membranes with gram-negative rods, other
      microbial species and negative cultures, respectively (p < 0.001). Preterm
      deliveries were also associated with significantly higher rates of bacterial
      vaginosis (38% vs. 14%) and isolation of vaginal pathogens (85% vs. 65%). In the
      case of the majority (88%) of chorioamniotic isolates the same species was
      isolated in the vagina. The findings suggest that gram-negative enteric rods are
      important placental pathogens responsible for sub-clinical chorioamnionitis and
      possibly preterm birth. The findings support the concept that microorganisms
      ascending from the lower genital tract produce local inflammation, which may
      result in preterm labour and delivery.

PMID- 9248745
TI  - Guidelines for the investigation of invasive fungal infections in haematological
      malignancy and solid organ transplantation. British Society for Medical Mycology.
AB  - Invasive fungal infections are increasing in incidence and now affect as many as
      50% of neutropenic/bone marrow transplant patients and 5 to 20% of solid organ
      transplant recipients. Unfortunately, many of the diagnostic tests available have
      a low sensitivity. The guidelines presented here have been produced by a working
      party of the British Society for Medical Mycology in an attempt to optimise the
      use of these tests. The yield of fungi from blood cultures can be increased by
      ensuring that at least 20 ml of blood are taken for aerobic culture, by using
      more than one method of blood culture, and by employing terminal subculture if
      continuous monitoring systems are used with a five-day incubation protocol. Skin
      lesions in febrile neutropenic patients should be biopsied and cultured for
      fungi. The detection of galactomannan in blood or urine is of value in diagnosing
      invasive aspergillosis only if tests are performed at least twice weekly in high
      risk patients. Antigen detection tests for invasive candidiasis are less
      valuable. Computed tomography scanning is particularly valuable in diagnosing
      invasive pulmonary fungal infection when the chest radiograph is negative or
      shows only minimal changes. Bronchoalveolar lavage is most useful in patients
      with diffuse changes on computed tomography scan. The major advances in the
      diagnosis of invasive fungal infection in patients with haematological malignancy
      or solid organ transplantation have been in the use of imaging techniques, rather
      than in the development of new mycological methods in the routine laboratory.

PMID- 9248748
TI  - Staphylococcal scalded skin syndrome in a neonate.
AB  - A case of staphylococcal scalded skin syndrome in a neonate caused by mother-to
      child transmission through breast-feeding is reported. Staphylococcus aureus
      isolates from mother and child were identified using random-amplified polymorphic
      DNA analysis, which is a simple and rapid method for comparing strains. This
      study confirms the need to avoid breast-feeding in cases of breast abscess.

PMID- 9248747
TI  - Viral replication in patients with concomitant hepatitis B and C virus
      infections.
AB  - The aim of this study was to assess the implications of dual infection with
      hepatitis B virus (HBV) and hepatitis C virus (HCV). The HBV and HCV status in
      100 patients with chronic hepatitis was analysed. HBV DNA was studied using
      liquid hybridization and the polymerase chain reaction (PCR). HCV viremia was
      measured using qualitative and quantitative PCR. The HCV genotype was determined
      by PCR. Patients were divided into three groups according to their HCV-RNA and
      HBsAg status: group I consisted of 40 patients with chronic hepatitis caused by
      HBV; group II, 40 patients with chronic hepatitis caused by HCV; and group III,
      20 patients infected with both viruses. The HBV-DNA level was higher in group I
      than in group III (66.4 vs. 11.5 pg/ml; p < 0.05). Quantification of HCV viremia
      revealed mean values of 36.9 copies x 10(5)/ml in group II and 5.5 copies/ml x
      10(5) in group III (p < 0.05). The mean aminotransferase level and histological
      activity were higher in group III. HCV genotype lb was the predominant type. The
      data suggest that there is reciprocal inhibition of viral replication in patients
      with dual HBV and HCV infection. Liver disease appears to be more severe in
      patients with chronic hepatitis B and C.

PMID- 9248746
TI  - Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus
      encephalitis in patients with AIDS.
AB  - A retrospective evaluation was conducted in patients with AIDS and an autopsy
      diagnosis of cytomegalovirus (CMV) encephalitis to determine the relevance of
      clinical and laboratory findings in establishing a diagnosis. On autopsy of 100
      patients, CMV encephalitis was diagnosed in 13 patients; eight had
      periventricular CMV encephalitis, four micronodular CMV encephalitis, and one
      both conditions. Seven patients had had a CMV infection previously (6 cases of
      retinitis, 1 case of colitis), and at the onset of encephalitis all of them were
      receiving a maintenance dose of ganciclovir. Examination of the CSF showed
      specific changes in patients with periventricular encephalitis. CT revealed no
      characteristic findings, while MRI showed an increased signal intensity on T2
      weighted images. CMV DNA amplification by nested PCR was performed in nine
      patients with CMV encephalitis; PCR was positive in eight patients whose CSF was
      collected during CMV encephalitis, and negative in one patient whose CSF was
      collected six months before death. In conclusion, some clinical findings suggest
      a presumptive diagnosis, especially of periventricular encephalitis, and nested
      PCR appears to be a reliable and rapid technique for making an antemortem
      diagnosis.

PMID- 9248749
TI  - One bolus dose of gentamicin and early oral therapy versus cefotaxime and
      subsequent oral therapy in the treatment of febrile urinary tract infection.
AB  - The efficacy and safety of two different regimens for parenteral treatment of
      presumed severe febrile urinary tract infection were compared in a randomized
      study. One hundred fifty-eight patients were treated with either cefotaxime 2 g
      i.v. twice daily for at least two days followed by norfloxacin 400 mg twice daily
      orally or one bolus dose of gentamicin 3 mg/kg i.v. and norfloxacin from the
      start. Three patients randomized to cefotaxime died. Of the 101 patients with
      verified urinary tract infection, clinical response to assigned therapy was seen
      in 79% and 74%, respectively. There was no difference in fever duration between
      the two regimens. The results indicate that one bolus dose of gentamicin with
      early oral therapy is a safe and effective alternative to common parenteral
      regimens for empirical treatment of febrile urinary tract infection.

PMID- 9248750
TI  - In vitro activity of trimethoprim against Borrelia burgdorferi.
AB  - A new culture medium has been developed to evaluate the activity of trimethoprim
      and sulfamethoxazole against Borrelia burgdorferi in vitro. In this specially
      modified Barbour-Stoenner-Kelly medium, in which antagonizing substances were
      reduced to a minimum, trimethoprim was more active against Borrelia burgdorferi
      than against a sensitive strain of Escherichia coli, but sulfamethoxazole was not
      active against Borrelia burgdorferi.

PMID- 9248751
TI  - Fatal Scedosporium prolificans infection in a leukemic patient.
AB  - The case is described of a 42-year-old patient with acute myeloid leukemia who
      received two courses of chemotherapy complicated by prolonged bone marrow
      depression. He was admitted to hospital with fever, hepatosplenomegaly and
      bilateral nodular pulmonary infiltrates. After admission diffuse cutaneous skin
      nodules, and hypodense lesions in the hemispheres and cerebellum developed.
      Cultures of cerebrospinal fluid, bronchoalveolar lavage fluid, skin biopsy
      specimens and blood revealed Scedosporium prolificans, indicative of disseminated
      mycosis. Treatment with amphotericin B and fluconazole was unsuccessful and the
      patient died within five days after admission. Features that may enhance early
      recognition of Scedosporium prolificans infection by both clinicians and
      microbiologists, as well as options in the treatment of infection with this
      fungal agent are discussed.

PMID- 9248753
TI  - Tumor necrosis factor alpha and interleukin 6 release induced by antibiotic
      killing of Pseudomonas aeruginosa and Staphylococcus aureus.
AB  - Using a recently described ex vivo model, tumor necrosis factor-alpha and
      interleukin-6 released by peripheral blood monocytes after killing of Pseudomonas
      aeruginosa and Staphylococcus aureus by ceftazidime, imipenem, and meropenem was
      measured. Cytokine release was highest with ceftazidime and lowest with imipenem
      for both bacteria (p < 0.05), although cytokine concentrations were much lower
      after killing of Staphylococcus aureus. Differences in cytokine release rates
      induced by various cell-wall active antibiotics have not yet been described for
      gram-positive organisms and should be studied further.

PMID- 9248752
TI  - Comparison of three commercial media for direct identification and discrimination
      of Candida species in clinical specimens.
AB  - One hundred and ninety-two clinical specimens were used to compare the three
      chromogenic media Albicans ID, Candiselect, and CHROMagar Candida to a standard
      method using a Sabouraud-chloramphenicol agar medium and standard methods for
      identification of yeasts. The detection rates were 83.79, 83.24, 86.59 and 84.91%
      respectively. For the chromogenic media, the rates of direct identification
      (growth plus specific pigmentation) for Candida albicans were 56.50, 37.68 and
      11.59% after 24 hours' incubation and 92.75, 91.30 and 88.57% after 72 hours'
      incubation respectively, with 100% specificity. Furthermore, CHROMagar Candida
      identified the five Candida tropicalis and the two Candida krusei strains
      detected after 48 hours' incubation.

PMID- 9248755
TI  - Usefulness of Leeds Acinetobacter Medium for recovery of Acinetobacter species
      from respiratory specimens collected in an intensive care unit.

PMID- 9248754
TI  - Vancomycin-resistant Bacillus circulans carrying the vanA gene responsible for
      vancomycin resistance in enterococci.

PMID- 9248756
TI  - Acute epididymo-orchitis due to Pseudomonas aeruginosa.

PMID- 9248757
TI  - Addition of lamivudine to the drug regimen in patients with advanced HIV disease
      on nucleoside therapy.

PMID- 9248758
TI  - Survey on rotavirus infections in a German pediatric hospital.

PMID- 9248759
TI  - Detection of methicillin-resistant Staphylococcus aureus using the BBL crystal
      MRSA kit.

PMID- 9248760
TI  - Drug prescription in diabetic patients in Stockholm in 1992 and 1995--change over
      time.
AB  - OBJECTIVE: To describe and compare the distribution of prescribed drugs in
      diabetic patients between 1992 and 1995. METHODS: Two cross-sectional surveys of
      a random selection of medical records of diabetic patients, from three community
      health centres (CHCs) in the Stockholm metropolitan area, were carried out. The
      age of the subjects ranged from 20 to 84 years. The number of prescriptions of
      pharmaceutical preparations given to the diabetic patients was noted, as well as
      classification of the diabetes, the metabolic outcome, and concomitant
      hypertension. RESULTS: Between 1992 and 1995, the use of oral antidiabetics
      increased significantly from 43 to 57% of the patients and the rate of treatment
      with diet only decreased from 30 to 20%. Combination treatment with oral drugs
      and insulin rose significantly from 1 to 8% of the patients. However, the
      greatest increase observed between 1992 and 1995 concerns cardiovascular drugs.
      The prescription rate of ACE inhibitors increased from 5 to 21%, of loop
      diuretics from 19 to 28%, of ASA from 9 to 21%, and of lipid-lowering agents from
      1 to 7%. There was also a considerable variation between the three CHCs. Despite
      the more aggressive diabetic treatment strategies, the metabolic state was
      unchanged and unsatisfactory for 40-50% of the patients. CONCLUSIONS: There have
      been major changes towards more active pharmacological treatment regarding
      antidiabetic, cardiovascular, and lipid-lowering agents.

PMID- 9248761
TI  - Improving utilization of intravenous immune globulin through concurrent use of an
      indication form.
AB  - OBJECTIVE: Based on the guidelines of the United States Joint Commission for
      Accreditation of Health Care Organizations for conducting a drug utilization
      evaluation, we evaluated the usage of intravenous immune globulin at our tertiary
      care hospital. METHODS: An initial concurrent evaluation of IVIG use showed
      deficiencies in both dosing and compliance with hospital policy, with regards to
      its use for unlabeled indications. Two follow-up evaluations were performed after
      the institution of an IVIG indication form, which was designed to accompany each
      order. RESULTS: We demonstrated consistent improvements in both dosing criteria,
      labeled IVIG use, and compliance with hospital policy its use in unlabeled
      indications. An ongoing prospective program targeting IVIG use, combined with the
      introduction of a simple indication form improved its utilization at our
      hospital.

PMID- 9248762
TI  - A dose-response study comparing suppression of plasma cortisol induced by
      fluticasone propionate from Diskhaler and budesonide from Turbuhaler.
AB  - OBJECTIVE: To compare the systemic potency of inhaled fluticasone propionate
      delivered via Diskhaler (FP-DH), and inhaled budesonide delivered via Turbuhaler
      (BUD-TBH) over the clinically recommended dose range using plasma cortisol
      suppression as a marker for systemic activity. METHODS: The systemic potency was
      examined in a dose-response study in 81 healthy male volunteers. The study was of
      an open, randomized, parallel-group (four groups) design, where two treatments
      were given in crossover fashion within each group. FP-DH and BUD-TBH were given
      b.i.d. for 7 days (14 doses): 100 and 100 micrograms (group 1); 200 and 200
      micrograms (group 2); 500 and 400 micrograms (group 3); 1000 and 800 micrograms
      (group 4). There was a washout period of 7 days within each treatment group. All
      doses were administered at 08:00 and 20:00 hours. Multiple plasma cortisol
      samples were taken every 2 h over 24-h periods prior to randomization (baseline)
      and during steady state (i.e., the last two dosing intervals). Cortisol
      suppression was determined by comparing average plasma concentrations of cortisol
      before and during treatment. Dose-response curves for cortisol suppression were
      analyzed using multivariate non-linear regression (Hill modeling). RESULTS:
      Multiple dosing for 7 days with FP-DH and BUD-TBH resulted in dose-dependent
      cortisol suppression by both drugs, most pronounced at the two highest dose
      levels. FP-DH-induced suppression was 41% at 500 micrograms and 86% at 1000
      micrograms b.i.d., while that induced by BUD-TBH was 19% at 400 micrograms and
      47% at 800 micrograms b.i.d. Statistically significant differences were found
      when comparing the two steroids at these two dose levels. Doses producing 50% of
      maximum suppression (ED50) were estimated at 833 micrograms b.i.d. for BUD-TBH
      and 479 micrograms b.i.d. for FP-DH. This gave an estimated relative cortisol
      suppression over the dose range of 1.74:1 (FP-DH:BUD-TBH). ED50 values, estimated
      from cortisol concentrations at 08:00 hours (12 h after the last dose), were 1212
      micrograms b.i.d. for BUD-TBH and 527 micrograms b.i.d. for FP-DH giving a
      relative cortisol suppression of 2.30:1 (FP-DH:BUD-TBH). Fourteen subjects on the
      highest FP-DH dose and 3 at the next highest dose had morning plasma cortisol
      levels below the lower reference limit. No subject taking budesonide, however,
      had morning plasma cortisol levels below the reference limit. Analysis of the
      time for return to pretreatment baseline levels showed that cortisol suppression,
      12-24 h after the last dose, was statistically significant compared with the
      baseline for the highest dose of FP-DH but not for any of the BUD-TBH doses.
      CONCLUSIONS: The results of the present study show that FP-DH suppresses plasma
      cortisol more than BUD-TBH on a equivalent basis with regard to both magnitude
      and duration.

PMID- 9248763
TI  - Adverse effects and compliance with mefloquine or proguanil antimalarial
      chemoprophylaxis.
AB  - OBJECTIVE: We had the impression that adverse reactions to standard antimalarial
      prophylaxis were reported much more often than stated by the package insert and
      medical drug references; and that side effects adversely affected compliance.
      Therefore, we evaluated adverse effects and compliance of the two standard
      malaria prophylactic regimens (mefloquine 250 mg per week and proguanil 100 mg
      twice per day) among short-term travellers. We expected that travellers who had
      experienced possible adverse effects on previous journeys might avoid
      antimalarial drugs on subsequent journeys (self-selection) and we therefore
      looked at adverse effects dependent on prior use. METHODS: The presence of
      neuropsychological and gastrointestinal symptoms were assessed by telephone
      interviewing of 300 travellers who had visited the travel vaccination service of
      our regional public health institute. Symptoms, prior use and non-compliance of
      104 mefloquine users and 103 proguanil users were compared with 93 non-users in
      order to control for travel-related symptoms. RESULTS: Mefloquine showed the
      following adverse effects: depression [excess risk (ER) 7.2 per 100 users],
      dizziness (ER 9.3) and itching (ER 12.3). Adverse effects of proguanil were
      dizziness (ER 7.5) and nausea (ER 12.7). Adverse effects were mostly mild to
      moderate and occurred mainly during the time abroad. These results did not change
      when adjusting for age, sex, or destination. For almost every symptom, we found a
      remarkable difference between the relationship of symptoms and antimalarial drugs
      in first-time users and that in prior users: in the first-time users the
      relationship was positive, while in prior users it was absent or negative. This
      could be due to self-selection or adaptation to adverse effects. 22% of
      mefloquine users were non-compliant, whereas 35% of proguanil users were non
      compliant. Adverse effects (experienced or expected) were the most often reported
      reason for mefloquine users to stop or even not to start taking the drug (42%).
      For proguanil, most of the non-compliant participants saw no point in starting or
      continuing its use (perceived uselessness 54%). CONCLUSION: We can confirm the
      reports by users that adverse effects of mefloquine and proguanil are common and,
      although mostly mild, adversely affect compliance. We suggest that a longer run
      in period for mefloquine as well as counselling travellers about possible adverse
      effects might improve compliance.

PMID- 9248764
TI  - Effects of calcitriol on eosinophil activity and antibody responses in patients
      with schistosomiasis.
AB  - OBJECTIVE: Parasitic infestations are known to elicit T-helper lymphocyte type 2
      (Th-2) reactions, characterized by a pronounced eosinophila and high IgE levels.
      In humans both elevated specific IgE levels and eosinophil counts are associated
      with resistance to reinfection with schistosomiasis. This study aimed to
      establish whether the Th-2 reaction could be enhanced with calcitriol (vitamin
      D3). Calcitriol has been shown to cause a shift from Th-1 to Th-2 type reactions
      when applied locally to the skin. METHODS: Fifty-nine patients with Schistostoma
      haematobium infection were randomized to one of four treatment modalities, i.e.
      (a) praziquantel (PZQ) 60 mg.kg-1 orally on day 1, (b) PZQ 60 mg.kg-1 on day 1
      plus calcitriol 1 microgram per day orally for 5 consecutive days, (c) calcitriol
      1 microgram per day for 5 consecutive days or (d) placebo. Blood for differential
      counts, eosinophil cationic protein (ECP), specific IgE and IgG to whole-worm
      antigen, as well as urine samples for egg counts, were collected on days 0 and
      21. RESULTS: Baseline values did not differ significantly between the groups.
      Calcitriol alone resulted in significant increases in circulating lymphocytes
      (median increase of 5.5%) and the percentage of eosinophil vacuolization (mean
      increase 28%). It, however, significantly decreased ECP levels (mean decrease
      46%). PZQ in combination with calcitriol significantly enhanced production of
      specific IgE (mean increase 213%) and IgG (mean increase of 170%) and tended to
      increase eosinophil vacuolization (mean increase 22%). All these changes also
      differed significantly from those in the placebo group. The specific IgE and IgG
      levels were also significantly higher than the already increased levels seen with
      PZQ treatment only. ECP levels were, however, not significantly affected by
      combination therapy, whereas PZQ alone significantly enhanced ECP production
      (mean increase 93%). CONCLUSIONS: The increases in specific IgE responses and
      percentage of eosinophil vacuolization favour a Th-2 type of reaction. The ECP
      values viewed in isolation may, paradoxically, indicate a Th-1 response; this
      could, however, have been an artefact due to the method of ECP detection ex vivo.
      Finally, it would seem that calcitriol does cause some immune augmentation when
      combined with PZQ therapy in patients with schistosomiasis. However, long-term
      follow-up is needed to prove that these findings would translate into resistance
      against re-infection.

PMID- 9248766
TI  - Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non
      insulin-dependent diabetic patients with renal impairment.
AB  - OBJECTIVE: A single oral dose of paracetamol (20 mg.kg-1) was given to 38 Chinese
      patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either
      normal renal function or varying degrees of renal impairment, with creatinine
      clearances ranging from 4 to 123 ml.min-1.1.73 m-2. The plasma and urinary
      concentrations of paracetamol and its major metabolites were measured by high
      performance liquid chromatography (HPLC). RESULTS: The absorption and elimination
      of paracetamol were unaffected by renal impairment. However, the area under the
      plasma concentration time curve and the elimination half-life of paracetamol
      metabolites increased significantly with worsening renal insufficiency. Mean
      renal clearances of paracetamol and its conjugates were significantly reduced in
      these subjects. There was no evidence of altered metabolic activation with renal
      impairment. CONCLUSION: The results demonstrate that paracetamol disposition is
      minimally affected by diabetic nephropathy; however, extensive accumulation of
      conjugates may occur.

PMID- 9248765
TI  - Effect of exogenous female sex-steroid hormones on beta 2-adrenoceptors in
      healthy males.
AB  - OBJECTIVE: We have previously demonstrated that exogenous progesterone, but not
      oestrogen, upregulated lymphocyte beta 2-adrenoceptors (beta 2-AR) when given
      during the follicular phase in healthy females. In the present study, we were
      interested to see whether this facilitatory effect of female sex-steroid hormones
      could be demonstrated in healthy males. METHODS: Nine healthy male volunteers
      with a mean age of 24 years completed this randomised, double-blind, placebo
      controlled, cross-over study. They were randomised to receive either oral
      placebo, oestradiol valerate (4 mg) or medroxyprogesterone (40 mg). The study
      medication was given in two divided doses 12 h apart. Subjects attended the
      laboratory at baseline (T0 is baseline), 1 h after ingestion of the second dose
      of study medication (T1) and 24 h later (T24). At each visit, 60 ml of peripheral
      blood was withdrawn for measurement of serum oestradiol, progesterone and
      testosterone levels, and for lymphocyte beta 2-AR parameters; density (Bmax),
      binding affinity (Kd) and maximal cyclic AMP response to isoprenaline (Emax).
      RESULTS: Baseline levels of sex-steroid hormones were comparable for each of the
      treatment periods. Serum oestradiol levels increased significantly, twofold, 1 h
      after ingestion of oestradiol but there was no significant change in levels of
      serum progesterone and testosterone. Lymphocyte beta 2-AR parameters following
      treatment with oestradiol and progesterone did not change significantly from
      baseline and were not different from placebo. CONCLUSION: In contrast to
      previously reported effects in women, female sex-steroid hormones did not appear
      to have any significant facilitatory effects on lymphocyte beta 2-AR parameters
      when given exogenously to healthy males. This lack of effect may be due either to
      the absence of receptors for female sex hormones in beta 2-AR or to reduced
      efficacy of female hormone-receptor coupling in male lymphocytes.

PMID- 9248767
TI  - Pharmacokinetics of nicardipine enantiomers in healthy young volunteers.
AB  - OBJECTIVES: The present study was conducted to compare pharmacokinetic behaviors
      of nicardipine enantiomers given in different doses with different formulations
      of racemic nicardipine in healthy volunteers. METHODS: One or two 20-mg racemic
      nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were
      administered to eight healthy volunteers in a crossover fashion and
      pharmacokinetic parameters were evaluated. Enantiomer concentrations were
      determined by GC-MS combined with chiral stationary phase HPLC. RESULTS AND
      CONCLUSIONS: Serum concentration of (+)-nicardipine was approximately 2-3 times
      higher than that of (-)-nicardipine in 20- and 40-mg doses of conventional
      formulations and a non-linear increase in bioavailability with dose was
      demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3-2.8
      times greater than that of the (-)-nicardipine (P < 0.05) when 20 and 40 mg
      racemic nicardipine were administered in a conventional preparation. Relative
      bioavailability of the sustained-release preparation vs the conventional
      preparation was 28% and 44% for (+)- and (-)-nicardipine, respectively, for the
      40-mg dose.

PMID- 9248768
TI  - Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation.
AB  - OBJECTIVE: A series of studies was undertaken to determine the cytochrome P450
      isoform(s) involved in naproxen demethylation and whether this included the same
      isoforms reported to be involved in the metabolism of other NSAIDs. METHODS: (S)
      Naproxen was incubated with human liver microsomes in the presence of a NADPH
      generating system and the formation of desmethylnaproxen was measured by high
      performance liquid chromatography (HPLC). To further clarify the specific
      isoforms involved, experiments were conducted with preparations expressing only a
      single P450 isoform (vaccinia virus-expressed cells and microsomes derived from a
      lymphoblastoid cell line, each transfected with specific P450 cDNAs) as well as
      inhibition studies using human liver microsomes and putative specific P450
      inhibitors. RESULTS: In human liver microsomes (n = 7), desmethylnaproxen
      formation was observed with a mean kM of 92 (21) mumol.l-1, Vmax of 538 pmol.min
      1.mg-1 protein and Cint2 (reflective of a second binding site) of 0.36
      microliter.min-1.mg-1 protein. This Cint2 term was added since Eadie-Scatchard
      analysis suggested the involvement of more than one enzyme. Studies using
      putative specific P450 inhibitors demonstrated inhibition of this reaction by
      sulfaphenazole, (apparent Ki = 1.6 mumol.l-1), warfarin (apparent Ki = 27 mumol.l
      1), piroxicam (apparent Ki = 23 mumol.l-1) and tolbutamide (apparent Ki = 128
      mumol.l-1). No effect was observed when alpha-naphthoflavone and troleandomycin
      were employed as inhibitors, but reaction with furafylline produced, on average,
      a maximum inhibition of 23%. At a naproxen concentration of 150 mumol.l-1,
      formation of desmethylnaproxen was observed in cells expressing P450 1A2, 2C8,
      2C9 and its allelic variant 2C9R144C. To further characterize these reactions,
      saturation kinetics experiments were conducted for the P450s 1A2, 2C8 and 2C9.
      The kM and Vmax for P450 1A2 were 189.5 mumol.l-1 and 7.3 pmol.min-1.pmol-1 P450,
      respectively. Likewise, estimates of kM and Vmax for P450 2C9 were 340.5 mumol.l
      1 and 41.4 pmol. min-1.pmol-1 P450, respectively. Reliable estimates of kM and
      Vmax could not be made for P450 2C8 due to the nonsaturable nature of the process
      over the concentration range studied. CONCLUSION: Multiple cytochrome P450
      isoforms (P450 1A2, 2C8 and 2C9) appear to be involved in naproxen demethylation,
      although 2C9 appears to be the predominant form.

PMID- 9248769
TI  - Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women
      during the second and third trimesters of pregnancy.
AB  - OBJECTIVE: Routine malaria prophylaxis with chloroquine (CQ) is recommended to
      pregnant semi-immune women in several countries in Africa. The dosage is
      empirically based. We investigated whether blood CQ concentrations and apparent
      oral blood clearance (CL/F) change during the course of pregnancy. We also
      studied whether malaria parasites could be detected together with low CQ blood
      levels. METHODS: Forty nine semi-immune Tanzanian women were recruited in the
      16th week of pregnancy. They were given 310 mg oral CQ base once per week as
      prophylaxis during the whole pregnancy. Capillary blood samples were taken for
      analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried
      on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence
      of malaria parasites. RESULTS: A total of 25 women fulfilled the sampling
      schedule. CL/F increased significantly from 160 ml.min-1 at week 26 to 180 ml.min
      1 at week 36. In 7 of 25 women, CL/F increased > 20%. Trough blood CQ
      concentrations, determined on four occasions at week 26 and at week 36 varied
      between 200 and 900 nmol.l-1. No statistically significant differences between
      occasions were seen. Malaria parasites were seen in two individuals early in
      pregnancy. CONCLUSION: Blood CQ CL/F showed a small increase during the course of
      pregnancy. The estimated mean blood CL/F values of 160 and 180 ml.min-1 (week 26
      and 36, respectively) were higher than the mean CL/F of 125 ml.min-1 in non
      pregnant individuals, published previously. Efficacy of higher dosages of CQ in
      malaria prophylaxis in pregnant women could, therefore, be evaluated in
      controlled trials in high-risk malaria areas.

PMID- 9248770
TI  - Pharmacokinetics and bioavailability of oral and intramuscular artemether.
AB  - OBJECTIVE: The pharmacokinetics and bioavailability of artemether and
      dihydroartemisinin were investigated in eight Thai males following the
      administration of single oral and intramuscular doses of artemether (300 mg) in a
      randomized two-way cross-over study. RESULTS: Both oral and intramuscular
      artemether were well-tolerated. In most cases, artemether and dihydroartemisinin
      were detected in plasma after 30 min and declined to levels below the limit of
      detection within 18-24 h. Compared with intramuscular administration, oral
      administration of artemether resulted in a relatively rapid but incomplete
      absorption [Cmax: 474 vs 540 ng.ml-1; tmax: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20
      micrograms.h.ml-1]. Geographic means of lag-time and absorption half-life (t1/2a)
      of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h,
      respectively, t1/2z was significantly shortened after the oral dose [2.8 vs 6.9
      h]. Mean oral bioavailability relative to intramuscular administration was 43.2%.
      The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower
      after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60).
      artemisinin, which is commercially available in China, Vietnam, Thailand and some
      African countries. The drug is administered as solution in oil for intramuscular
      injection or as oral tablets. The clinical efficacy of artemether is dependent on
      the formulation, dosing scheme, duration of treatment, and the severity of the
      disease [1, 2]. Oral artemether is effective but with short-term treatment, the
      relapse rate is high. While the efficacy of intramuscular artemether against
      multidrug-resistant P. falciparum in either uncomplicated or severe cases has
      been confirmed, its pharmacokinetic documentation is limited. Formulations with
      high bioavailability and low costs are essential. With high-performance liquid
      chromatography and electrochemical detection, more sensitive and reliable assay
      of artemisinin and derivatives in biological fluids has been achieved [3-4]. In
      the present study, we have assessed the pharmacokinetics and bioavailability of
      oral and intramuscular artemether, in healthy Thai males.

PMID- 9248771
TI  - The cardiac effects of terfenadine after inhibition of its metabolism by
      grapefruit juice.
AB  - OBJECTIVE: To determine whether the pharmacokinetics and electrocardiographic
      pharmacodynamics of terfenadine are affected by the concomitant administration of
      grapefruit juice. METHODS: Six healthy volunteers were recruited for a balanced
      cross-over study. Each volunteer received 120 mg terfenadine 30 min after
      drinking 300 ml of either water or freshly squeezed grapefruit juice. The
      alternative treatment was administered on the second study day 2 weeks later.
      Measurements of the area under the terfenadine plasma concentration-time curve
      (AUC), maximum terfenadine concentration (Cmax) and the time to maximum
      concentration (tmax) were made, and the corrected QT (QTc) interval was measured
      from the surface electrocardiogram. RESULTS: Terfenadine was quantifiable in
      plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC
      of terfenadine was significantly increased by concomitant grapefruit
      administration (median values 40.6 vs 16.3 ng.ml-1.h), as was the Cmax (median
      values 7.2 vs 2.1 ng.ml-1). The tmax was not significantly increased and there
      was no significant change in the median QTc interval despite the increased
      terfenadine levels. The 95% confidence interval for the difference in the change
      in QTc interval at Cmax was -13 to +38 ms. CONCLUSION: Administration of
      grapefruit juice concomitantly with terfenadine may lead to an increase in
      terfenadine bioavailability, but the increase observed in this study did not lead
      to significant cardiotoxicity in normal subjects. However, this does not exclude
      the risk of cardiotoxicity in high-risk subjects given greater doses of
      grapefruit juice over longer periods of time.

PMID- 9248772
TI  - An evaluation of linearity of kinetics for the neuroleptics perphenazine and
      zuclopenthixol.

PMID- 9248773
TI  - Comparative bioavailability of two vitamin B1 preparations: benfotiamine and
      thiamine mononitrate.

PMID- 9248774
TI  - Benzodiazepine consumption in Spain.

PMID- 9248775
TI  - On sample sizes for bioequivalence studies with inhaled corticosteroids.

PMID- 9248776
TI  - Involvement of the rat gut epithelial and muscular layer, and microflora in
      chiral inversion and acyl-glucuronidation of R-fenoprofen.
AB  - In the presence of excised human and rat gut, the pharmacologically inactive R
      enantiomers of both ibuprofen and fenoprofen (FN) are bioinverted to their anti
      inflammatory antipodes. In an attempt to further localize the site of inversion,
      we incubated R-FN, in oxygenated (O2:CO2, 95:5, v/v) Krebs-Henseleit solution (37
      degrees C, pH 7.4) for 3 h in the presence of the intestinal contents, epithelium
      and muscular layer of upper jejunum and everted jejunum sack of antibiotic
      treated (500 mg/kg neomycin and erythromycin b.i.d. for 3 days) and control adult
      female Sprague-Dawley rats. The formation of S-FN and acylglucuronidated FN was
      examined in the incubation medium using a stereospecific HPLC assay. The
      metabolic activities are reported per g of wet tissue. The extent of inversion by
      the everted rat gut was substantial (30.7 +/- 5.1%) but no significant
      differences between the control and germ-eradicated rats was observed. The
      epithelial cells were found to be the major site of inversion in the intestinal
      wall (37.5 +/- 4.7%) with the muscular layer (7.8 +/- 2.1%) and intestinal
      contents (5.7 +/- 2.2%) contributing only to a small extent to the process. Both
      enantiomers were substantially acyl-glucuconjugated in the epithelial and
      muscular layers, and the intestinal content.

PMID- 9248777
TI  - Pharmacokinetics of mirtazapine from orally administered tablets: influence of a
      high-fat meal.
AB  - The effect of a high-fat meal on the pharmacokinetics of mirtazapine was studied
      in 19 healthy normal young male volunteers. In a randomized two-period crossover
      study, each volunteer received an oral dose of 15 mg of mirtazapine in the form
      of tablets, in the fasting state and after a high-fat meal, with a washout period
      of 14 days between the two doses. Serial blood samples were taken and
      pharmacokinetic parameters calculated and statistically analyzed from mirtazapine
      plasma levels. The extent of absorption of mirtazapine, as measured by the area
      under the plasma level versus time curve, was found to be equivalent for the
      fasting and the fed state. Food intake was shown to have no influence on the
      elimination of mirtazapine, as measured by its elimination half-life. The rate of
      mirtazapine absorption, as measured by the peak level (Cmax), was not altered by
      food. The peak time (tmax), however, in subjects in the fed state showed an
      increase: the 90%-confidence interval for the median difference ranged from 0.25
      to 1.25 h. This was the only effect of food found in this study. It is considered
      to be of no clinical consequence.

PMID- 9248778
TI  - Metabolism studies on transdermal prostaglandin E1 in human foreskin in vitro.
AB  - The metabolism of prostaglandin E1 (PGE1) in solution and in transdermal
      liposomal formulations was investigated in vitro by incubation with homogenates
      from human foreskin (HSH), with rabbit lung (RLH) and human placenta (HPH) and
      heat denatured homogenates as controls, PGE1 and its metabolites and degradation
      products were analyzed by reversed phase HPLC. Metabolism of PGE1 in HSH was
      negligible up to 5 h whereas at 24 h, 83 +/- 1%, 92 +/- 2%, and 84 +/- 3% of the
      initial drug content remained from two different liposomal PGE1 and the free drug
      incubations, respectively. In HPH, 65 +/- 4% and 5 +/- 3% of initial PGE1 content
      remained, whereas in RLH, 73 +/- 2% and 60 +/- 3% PGE1 remained after 1 h and 24
      h, respectively. The major metabolite was 15-ketoPGE1 in all homogenates. The
      specific 15-hydroxyprostaglandin dehydrogenase (15-OHPGDH) enzyme activities in
      HSH, RLH and HPH were found to be 0.22, 1.65, 5.29 nmol 15-ketoPGE1/h/mg
      homogenate protein, respectively. In conclusion, 15-OHPGDH activity was
      demonstrated in human foreskin. Encapsulation of PGE1 into liposomes can provide
      protection from skin metabolism. Based on our in vitro data, we predict that in
      vivo transdermal delivery of PGE1 is not limited by cutaneous metabolism.

PMID- 9248780
TI  - Deuterium isotope effects on caffeine metabolism.
AB  - The aim of this work was to study the influence of labelling on caffeine
      metabolism according to the incubation mode. It has been observed that labelling
      induces an isotopic effect on metabolisation speed: apparent half-lives are
      systematically increased. Moreover, isotopic effects are in agreement with those
      previously observed for retention times. Qualitatively, caffeine labelling
      systematically induces metabolic variations to the detriment of the metabolic
      pathway that induces the loss of the trideuteromethyl group. Caffeine
      accumulation and the release of the main metabolites have been studied with
      respect to isotopic effects on crossing the cell membrane. It has been
      demonstrated that, in most of the cases, accumulation decreased and that either
      metabolite release was increased or no isotopic effect was observed.

PMID- 9248779
TI  - The effect of velnacrine on the mixed function oxidase system.
AB  - Velnacrine is a centrally acting anticholinesterase which has been considered for
      use in the treatment of Alzheimer's disease. If proven to be of value, it will be
      used concurrently with other medications. Its potential to cause interaction is,
      therefore, important to study. The aim of this work was to investigate velnacrine
      as an inhibitor of hepatic oxidative enzymes. The effects of velnacrine on
      antipyrine metabolism in isolated rat hepatic microsomes were compared to those
      of cimetidine. Aliquots of 200, 250 and 300 micrograms/ml antipyrine were
      incubated alone, with 20 micrograms/ml cimetidine and with each of 20, 50 and 100
      micrograms/ml velnacrine. The concentrations of antipyrine and of its
      metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine
      were assayed by reverse phase high performance liquid chromatography. Cimetidine
      inhibited production of all three metabolites. Velnacrine did not affect 3
      hydroxymethylantipyrine production. Mean inhibition of 4-hydroxyantipyrine
      production of 15%, 30% and 25% (P < 0.01), and of 14%, 25% and 12% of
      norantipyrine production (P < 0.01) occurred. These results indicate that
      velnacrine may inhibit the enzymes responsible for the metabolism of antipyrine
      to norantipyrine and 4-hydroxyantipyrine. The clearance rate of drugs that are
      metabolised through the hepatic oxidase system may, therefore, be reduced in the
      presence of concurrent treatment with velnacrine.

PMID- 9248781
TI  - Maximal biliary transport of sulfobromophthalein in patients with a T-tube placed
      in the common bile duct.
AB  - In 19 adult patients with choledocholithiasis who were operated on, excretion of
      free and conjugated sulfobromophthalein (BSP) in the bile collected through a T
      tube inserted in the common bile duct was determined. The transport maximum (Tm)
      for BSP was calculated by the constant-infusion technique after an intravenous
      infusion of the dye at a rate of 0.3 and 0.09 mg/kg/min for the first and second
      hour, respectively. Free and conjugated BSP were measured in blood samples
      obtained at 30, 40, and 50 min of each hourly-infusion period, and in bile
      collected during the first 30 min (sample A) and between 30-50 min (sample B)
      after starting the first BSP infusion, and during the first 30 min (sample C) and
      between 30-50 min (sample D) after starting the second infusion. No correlations
      between Tm of BSP and glutathione transferase activity and between Tm and
      bilirubin and alkaline phosphatase in serum were found. Although there was an
      overall correlation between Tm of BSP and biliary excretion of BSP after 30 min
      of starting the BSP infusion (samples B, C and D) (r = 0.4716; P = 0.41), Tm
      values were always lower than recoveries of free BSP in bile. It seems that Tm of
      BSP (measured with the Wheeler's method) overestimates the actual values of
      biliary excretion of free BSP, and that the percentage of conjugated BSP in serum
      is related to the degree of impairment of biliary transport of BSP.

PMID- 9248782
TI  - Tonsillar diffusion kinetics of amoxycillin after oral administration of 1 g to
      adults.
AB  - Although amoxycillin is widely used to treat pharyngo-tonsillitis, the kinetics
      of tonsillar diffusion have rarely been studied. The aim of this work was to
      study the kinetics of amoxycillin diffusion in the tonsils of adults, by
      measuring tonsillar concentrations 1.5, 3, 6 and 12 h after oral administration
      of 1 g of amoxycillin (Clamoxyl dispersible tablet, 1 g) relative to concomitant
      serum levels by using an HPLC method and a microbiological technique. At
      enrollment, the 20 patients were randomly divided into four groups of five,
      corresponding to the time intervals (1.5, 3, 6 or 12 h) between the third
      amoxycillin intake and the start of surgery. The results given by the two assay
      methods correlated well (r = 0.92-0.99). Amoxycillin showed excellent penetration
      into the tonsils, with both tonsillar and serum concentrations exceeding the MIC
      for most pathogens encountered in this setting (including Streptococcus
      pyogenes), even 12 h after repeated dosing with 1 g of amoxycillin.

PMID- 9248783
TI  - Influence of route of administration and dosage form in the pharmacokinetics and
      bioavailability of salbutamol.
AB  - The present study was carried out to define the pharmacokinetics of salbutamol
      sulfate administered to mongrel dogs in five pharmaceutical forms via two routes
      of administration. One pharmaceutical form was administered intravenously
      (Ventolin i.v.) while the other four were administered orally (Ventolin:
      immediate-release formulation, Volmax: commercial osmotic pump, SG7 and SG14:
      sustained-release hydrophilic matrices developed in our laboratory). We obtained
      a first-order release kinetic of the salbutamol from Ventolin and SG7, whereas a
      zero-order release kinetic was observed for SG14 and Volmax formulations. Oral
      bioavailability was 80% and there were neither significant differences (P > 0.05)
      in terms of the calculation method used (relation of the areas under the plasma
      level curve Loo-Riegelman, deconvolution) nor in terms of the dosage form
      (Ventolin Volmax, SG7 and SG14). The elimination half-life value of salbutamol
      was 1.2 h when administered intravenously; this parameter had a value of 3.0 h
      for the immediate-release formulation and ranged between 5.4 and 7.2 h in the
      sustained-release formulations when administered orally. These changes in the
      half-life value of the sustained-release formulations will allow us to modify the
      frequency of administration in relation to immediate-release formulations.

PMID- 9248784
TI  - Variability of diphenhydramine N-glucuronidation in healthy subjects.
AB  - The H1-antagonist diphenhydramine can undergo direct glucuronidation at its
      tertiary amino group with formation of a quaternary ammonium glucuronide. The
      intraindividual variability in the amount of N-glucuronide excretion in urine was
      investigated in two female volunteers who repeatedly took single doses of 25 mg
      diphenhydramine hydrochloride without and with concomitant administration of
      ascorbic acid or ammonium chloride for urine acidification. Another two female
      and four male subjects underwent single tests without and with additional
      ascorbic acid. Diphenhydramine N-glucuronide quantities in urine differed
      significantly among subjects and ranged between 2.7% and 14.8% of the dose within
      8 h. Neither ascorbic acid nor ammonium chloride significantly influenced the
      quantity of N-glucuronide in urine, but ammonium chloride, that in contrast to
      ascorbic acid proved effective in lowering urinary pH, increased the excretion of
      the parent drug.

PMID- 9248785
TI  - In vitro studies on the metabolic fate of mifentidine, a novel histamine H2
      receptor antagonist.
AB  - The in vitro metabolism of mifentidine and several of its metabolites was studied
      using hepatic microsomes from seven animal species. The effects of potential
      enzyme inducers, inhibitors and activators were also studied. Mifentidine
      metabolites identified and characterised were: 4-imidazolylphenylamine (amine), 4
      imidazolylphenyl-formamide (formamide), the urea derivative of mifentidine (urea)
      and the imidazole-hydroxylated derivative of the amine (i-OH-amine), along with
      three unidentified metabolites, M1, M2 and M3. Evidence for the presence of the
      amine, formamide, urea and i-OH-amine was obtained by comparison with authentic
      reference compounds: (i) HPLC retention times; (ii) UV spectra; and (iii) MS
      spectra of metabolites. The postulated intermediates are: carbinolimine (for
      formamide, amine, i-OH-amine and urea formation); formamide (for amine and i-OH
      amine formation); amine (for i-OH-amine formation), and nitrone (for urea
      formation). One 'metabonate' of mifentidine was also identified, namely the nitro
      analogue of the amine. A possible prerequisite for the formation of this nitro is
      the corresponding hydroxylamine or nitroso compound. Cytochromes P450I and P450II
      were shown to be involved in the in vitro microsomal biotransformation of
      mifentidine, but the involvement of the flavin monooxygenase system was not
      proven.

PMID- 9248786
TI  - Interaction of chlormezanone with rat liver microsomes and its degradation.
AB  - Chlormezanone binds to oxidized cytochrome P450 in rat liver microsomes with a
      binding curve according to type I like hexobarbital but less pronounced and with
      a general shift to the left. Ethylmorphine N-demethylation, ethoxycoumarin and
      ethoxyresorufin O-deethylation are inhibited by chlormezanone in mM
      concentrations only whereas pentoxyresorufin O-depentylation is inhibited by
      about 50% in microM concentrations. Luminol and lucigenin amplified
      chemiluminescence indicating the formation of reactive oxygen species was not
      influenced in concentration ranges between mM and microM, whereas NADPH/Fe
      stimulated lipid peroxidation showed a tendency of inhibition. But scavenger
      activity could not be demonstrated: the zymosan stimulated chemiluminescence of
      whole blood was not influenced significantly. The degradation process of
      chlormezanone was elucidated. The first step involves ring opening by chemical
      hydrolysis with subsequent formation of an unstable acylhalfaminal which is the
      source of 4-chlorobenzaldehyde. This aldehyde undergoes enzymatically controlled
      oxidation to 4-chlorobenzoic acid which is the parent compound of following phase
      II reactions. The second degradation product is 2-carboxyethane-sulfinic-acid-N
      methylamide, which is hydrolyzed very quickly. Neither oxidation of the sulfinic
      acid or its N-methylamide derivative could be observed nor N-demethylation of
      chlormezanone.

PMID- 9248788
TI  - Multiple-dose pharmacokinetics of a long half-life drug: contributions of
      mathematical modeling.
AB  - A mathematical model was found that consistently described diverse
      pharmacokinetic data for a development compound from three pharmacokinetic
      studies in healthy volunteers and two efficacy and safety studies in patients.
      The model provided: quantification of demographic and random sources of
      pharmacokinetic variability; estimation of important pharmacokinetic parameters
      from sparse data; and explanation of observed patterns of pharmacokinetic
      response.

PMID- 9248787
TI  - In vitro toxicity and formation of early conjugates in Caco-2 cell line treated
      with clenbuterol, salbutamol and isoxsuprine.
AB  - Caco-2, human intestinal cell line able to differentiate in long-term culture,
      has been used to assess the cytotoxicity of the beta-agonists clenbuterol,
      salbutamol and isoxsuprine, also used at high doses to obtain lean meat in food
      producing animals, and to investigate the eventual in vitro formation of early
      conjugates of these compounds. For this purpose, the cells have been
      characterized for the activity of UDP-glucuronyltransferase, which is present and
      increases in the differentiated cells, and for the beta-receptors' binding
      characteristics, which are those of beta 1 and beta 2 subtypes. Isoxsuprine was
      shown to be the most toxic, followed by clenbuterol and salbutamol. Conjugates
      have been observed after incubation of the cells both with the lowest isoxsuprine
      and the highest salbutamol concentrations. No conjugates were detected in the
      case of clenbuterol.

PMID- 9248790
TI  - Infarction of the corpus callosum: computed tomography and magnetic resonance
      imaging.
AB  - OBJECTIVE: To describe the computed tomography (CT) and magnetic resonance (MR)
      features of corpus callosum (CC) infarctions. METHODS: We reviewed
      retrospectively 352 consecutive cranial CT and MR scans showing cerebral
      infarcts. Involvement of the CC was identified in 28 patients. RESULTS:
      Infarctions of the CC were diffuse (n = 3) or focal (n = 25). The former were
      seen in the setting of diffuse cerebral ischemia secondary to cardiopulmonary
      arrest or status epilepticus. The latter were divided into those affecting
      predominantly the genu, body or splenium. The most common location of the insult
      was the splenium (n = 13), followed by the body (n = 6) and genu (n = 3). In the
      remaining three patients combined genu/body infarctions were seen. CONCLUSION:
      Infarction of the CC may be more common than previously thought and is most often
      the result of cerebral embolism. MR is better suited than CT for the detection of
      vascular lesions of the CC.

PMID- 9248789
TI  - Cefixime absorption kinetics after oral administration to humans.
AB  - Cefixime (CFX) absorption kinetics after oral administration to humans was
      studied. Four distinct models, incorporating a delay of absorption and first
      order elimination kinetics, i.e. first-order absorption (M1), zero-order
      absorption (M0), Michaelis-Menten type absorption (MM) and Michaelis-Menten type
      absorption with 'an absorption window' (MM-delta t) were used to fit
      concentration data of CFX in 10 Chinese men following an oral dose of 400 mg. r2
      and AIC were selected as measures of goodness-of-fit. The results show that the
      MM-delta t model provided a better fit than the other three models. The kinetic
      parameters were estimated as follows: Vmax' = 10.80 +/- 3.80 mg.l-1.h-1; K(m)' =
      88.31 +/- 2.75 micrograms.ml-1; delta t = 4.75 +/- 0.85 h; T1/2 = 4.20 +/- 0.92
      h; Tmax = 5.20 +/- 0.92 h; and Cmax = 6.04 +/- 1.70 mg.l-1.

PMID- 9248791
TI  - Degree of carotid artery stenosis. Comparison of selective and non-selective
      angiographic findings with surgical specimens.
AB  - OBJECTIVE: To compare the degree of vessel narrowing seen on selective and non
      selective carotid artery catheter angiograms using criteria set by NASCET and
      ECST with the results obtained from corresponding surgical specimens. SUBJECTS:
      In 40 preoperative angiograms (20 non-selective, 20 selective) the 'distal'
      degree of internal carotid artery (ICA) stenosis according to NASCET criteria and
      the 'local' degree of stenosis according to ECST criteria was assessed. These
      data were compared with the 'distal' and 'local' degree of ICA stenosis obtained
      by measuring the specimens and the diameter of the distal ICA intraoperatively.
      RESULTS: The median 'local' degree of stenosis was 86.5% in the specimen and
      83.5% in the selective angiograms (difference not significant). In non-selective
      angiography the median 'local' degree of stenosis was 77.5% compared to 84% in
      the corresponding specimens (P < 0.01). The median 'distal' degree of stenosis in
      selective angiography was 76.5 versus 75.5% in the specimens (n.s.). The median
      'distal' degree of non-selective angiography was 67% compared to 77.5% in the
      corresponding specimens (P = 0.02). The trend to underestimate high grade
      stenosis (above 90%) was more pronounced in non-selective than in selective
      angiography. Medium grade stenosis (60-80%) was slightly overestimated in
      selective angiography. CONCLUSION: Selective angiography is more accurate in
      determining the 'true' degree of stenosis in internal carotid artery disease,
      taking into account a slight overestimation of medium grade stenosis. High grade
      stenosis is underestimated in both selective and non-selective angiography. These
      observations extend to both the ECST and NASCET criteria of measuring the degree
      of stenosis, which differ by about 10%.

PMID- 9248792
TI  - CT angiography of intracranial aneurysms: advantages and pitfalls.
AB  - OBJECTIVE: To determine the clinical usefulness of computed tomography (CT)
      angiography in the evaluation of cerebral aneurysms. MATERIALS AND METHODS: From
      October 1994 through April 1996, 26 patients with 30 surgical proven intracranial
      aneurysms underwent both CT angiography and catheter cerebral angiography. The
      findings of the two methods were reviewed independently and then compared with
      each other. RESULTS: Comparing with catheter angiography, CT angiography was
      superior in demonstrating the aneurysmal neck in seven aneurysms but was inferior
      in one. The thrombosed part and calcification of aneurysms were clearly
      demonstrated on CT angiograms. CT angiography also aided in differentiating tight
      vascular loops from aneurysms. On CT angiograms, one posterior communicating
      arterial aneurysm was overlooked and another anterior choroidal artery aneurysm
      was misinterpreted as a posterior communicating artery aneurysm. Of note were two
      patients in whom the infundibulum of the orbitofrontal artery was misinterpreted
      as the anterior communicating artery aneurysm. CONCLUSION: CT angiography can
      compliment conventional catheter angiography for its better demonstration of the
      3-dimensional anatomy. It can provide surgical information about the neck,
      calcification and thrombosed part of an aneurysm and its relation to adjacent
      structures. However, caution is advocated because CT angiography may fail to
      demonstrate small but important vessels such as posterior communicating, anterior
      choroidal and orbitofrontal arteries. Recognition of the limitations of CT
      angiography is important in minimizing interpretation errors.

PMID- 9248793
TI  - Cortical hypoperfusion in symptomatic West syndrome. A SPECT study.
AB  - Diffuse and focal changes in glucose utilization and abnormal cerebral cortical
      perfusion were found in West syndrome by PET and SPECT investigations. In this
      study 99mTc-HMPAO SPECT was performed on seven patients with symptomatic West
      syndrome several months after the onset of the spasms. Regions of interest of the
      cerebral cortex and cerebellum were delineated by an automated computer program
      and cortical/cerebellar ratios of the HMPAO uptake in the patients were compared
      to those of controls. The basal ganglia/cerebellar ratios were compared after
      manual placement of regions of interest. Significantly reduced perfusion was
      found in the bilateral anterior, mid frontal and perisylvian cortex, and in the
      left posterior frontal and temporal areas. Well localized, focal changes in the
      cortical perfusion were not found and the perfusion in the basal ganglia proved
      to be normal. These abnormalities in the cortical perfusion may reflect a pre
      existing brain pathology together with an encephalopathy due to the
      hypsarrhythmia and infantile spasms.

PMID- 9248794
TI  - Cystic meningiomas, a diagnostic and pathogenic challenge.
AB  - A 55-year-old woman presented with focal seizures, then rapidly evolving
      hemiplegia. Brain CT and MRI showed a large cystic lesion of the right frontal
      lobe with a small enhancing nodule adjacent to the dura. The nodule corresponded
      to a meningioma on pathological examination, and the operative findings suggested
      that the cyst was due to local entrapment of CSF by the tumor and its arachnoid
      adhesions. The rapid clinical deterioration was probably due to the rapid
      expansion of the cyst volume. Pathogenesis and unusual radiological appearances
      of cystic meningiomas are discussed.

PMID- 9248795
TI  - Tumor extent of slowly progressive oligodendroglioma determined by 18F
      fluorophenylalanine positron emission tomography.
AB  - We report the use of positron emission tomography (PET) and 18F
      fluorophenylalanine (18F-Phe) to determine the extent of a slowly progressive
      oligodendroglioma, which gradually grew over 10 years after the onset of
      convulsions. The tumor exhibited intense accumulation of 18F-Phe and was easily
      distinguished from the surrounding brain tissue. The tumor lesion indicated by
      18F-phe PET was more extensive than the lesion detected by computerized
      tomography (CT) and was comparable to the hypointense lesion detected by T2
      weighted magnetic resonance imaging (MRI). The tumor, a histologically verified
      oligodendroglioma, was extensively resected, and its extent corresponded to the
      high uptake region of 18F-Phe. The accuracy of the 18F-Phe PET technique for
      determining the extent of a tumor is valuable and will aid in the selection of an
      appropriate therapy modality for the management of oligodendrogliomas.

PMID- 9248796
TI  - Calcified, cystic brain metastases.
AB  - Calcifications are uncommon in metastases. Adenocarcinoma, osteopenic,
      osteosarcoma, lung and breast carcinoma can be the origin. A rare case of
      calcified cystic brain metastasis deriving from papillary cystadenocarcinoma is
      reported.

PMID- 9248797
TI  - Unusual appearance of an intracranial metastatic adenoid cystic carcinoma: comedo
      necrosis showed very hyperdense nodules on CT scans.
AB  - A case of intracranial metastatic adenoid cystic carcinoma with unusual
      hyperdense nodules in CT scans is described. A 32-year-old man had a brain tumor
      containing scattered and very hyperdense numerous nodules on CT scans. Initially,
      the hyperdense nodules were considered as intratumoral calcifications. The tumor
      subsequently proved to be metastatic adenoid cystic carcinoma through surgery.
      However, there were no calcium deposits in the surgical specimen. We observed
      only multiple central comedo-necrosis that could be the cause of the hyperdense
      lesions on CT scans.

PMID- 9248798
TI  - Reversible intracranial changes in eclampsia demonstrated by MRI and MRA.
AB  - CT and MRI allow visualization of eclampsia changes in the brain. Once case with
      reversible changes is reported.

PMID- 9248799
TI  - Peripheral nerve schwannoma preoperatively diagnosed by sonography: report of
      three cases and discussion.
AB  - The preoperative diagnosis of peripheral nerve schwannoma was correctly made by
      US in 3 patients referred to US because of upper extremity palpable mass. The
      patients complained of no pain and neurological symptoms, except in two cases
      where there was painful sensation radiating distally during lesion compression.
      In all cases, sonography demonstrated a sharply delineated hypoechoic homogenous
      mass with distal acoustic enhancement. The lesions were noted to be in a direct
      continuity with the cord-like echogenic structure consistent with a nerve. These
      features enabled a reliable diagnosis of peripheral nerve tumor, most likely
      schwannoma, to be made. Following a surgical excision, the diagnosis of
      schwannoma was confirmed by histopathology in all cases.

PMID- 9248800
TI  - Multiple organ involvement in tuberous sclerosis.
AB  - Tuberous sclerosis is an uncommon heredito-familial disease. A rare case of
      multiple organ involvement is reported.

PMID- 9248801
TI  - Organ doses, detriment and genetic risk from simple X-ray examinations in Malaga
      (Spain).
AB  - This work has been carried out with the aim of evaluating, as a reference, some
      radiological magnitudes which affect patients receiving radiation from X-ray
      sources. The sample was the population tended by the Radiological Service of the
      'Na, Sra, de la Victoria' University Hospital and who have been treated with some
      of the five simple explorations: chest, abdomen, lumbar spine, hip and pelvis.
      The primary beam of radiation delivered by the different generators have been
      measured by means of non-invasive methods, which allows us to estimate the
      effective dose. Likewise, we have evaluated the dose in gonads and the
      contribution that each technique provides to the genetically significant dose
      (GSD = 158.59 microGy) and to the somatic significant dose (SSD = 3.19 mSv-year).
      Moreover, we have calculated the annual dose per capita (0.15 mSv) and the
      contribution that performs to the detriment (G) of these tests of conventional
      radiology. The results obtained are analogous to the reference values proposed in
      the area of E.C.M. Furthermore, we also include the values of child expectancy
      and the number of exploration performed in the Health Sanitary Area Malaga-West
      classified according to type, age and sex of the patient.

PMID- 9248802
TI  - MR angiography of the renal artery: comparison of breath-hold two-dimensional
      phase-contrast cine technique with the phased-array coil and breath-hold two
      dimensional time-of-flight technique with the body coil.
AB  - Breath-hold 2D phase-contrast (PC) cine MR angiography with a phased-array coil
      and 2D time-of-flight (TOF) MR angiography were performed in the renal arteries
      and their findings were compared. Breath-hold 2D thin slice PC and TOF MR
      angiography were performed in 10 normal volunteers for renal arteries. A PC
      technique with k-space segmentation was utilized with the phased-array coil. A PC
      technique provided visualization of the renal artery more distally than a TOF
      technique (4.8 +/- 0.5 cm vs. 3.7 +/- 0.8 cm). With cardiac triggering, distal
      renal arteries were well demonstrated in PC MR angiography. On PC images, up- or
      downward movements of the mid to distal renal arteries with aortic pulsatility
      were recognized. The quality of the images was better with the PC than with the
      TOF technique (3.4 vs. 2.7). The mid to distal portions of the renal arteries
      translationally move with aortic pulsatility. To consistently visualize and
      evaluate them on MR angiography, cardiac triggering might be required to reduce
      the effects of pulsatile motions of the renal artery in the use of a phased-array
      coil.

PMID- 9248803
TI  - Echo-Doppler-flowmetric assessment of penile dorsal arteries and their role in
      the erectile mechanism.
AB  - Echo-doppler-flowmetric investigation is the best non-invasive technique for
      evaluating vascular dynamics of the erection mechanism. Previous studies were
      carried out with the aim of obtaining some reference parameters for healthy
      subjects and for subjects affected by impotence with different etiology. All of
      these studies focused on the penile cavernous artery, neglecting the role played
      by the penile dorsal artery in the erection process. In this study we examined
      the flowmetric pattern of the penile dorsal artery before and after
      intracavernous injection of PGE1 10 micrograms. A significant increase in the
      velocity of systolic and diastolic velocity was observed in dorsal arteries after
      intracavernous injection (P < 0.0001) in control subjects and in non-arteriogenic
      impotent patients. Moreover, the systolic velocity of dorsal arteries presents,
      after pharmacological stimulation, a statistically significant difference in
      comparison to the homolateral cavernous artery in non-arteriogenic impotent
      patients and in healthy subjects. In patients with arterial insufficiency, the
      absence of the dorsal artery was observed in 5 cases. Furthermore, the systolic
      velocity of dorsal arteries turns out to be significantly lower than the systolic
      velocity of dorsal arteries in normal subjects; it is, however, higher than the
      reference standard for arteriogenic impotent patients. It is likely that the
      penile dorsal artery, because of its extensive vascular connections with the
      cavernous artery, provides a hemodynamic support, which can counterbalance slight
      disorders of cavernous arteries. When the dorsal artery is absent (agenesis,
      aplasia), or diseased, even slight alterations can result in an early onset of
      erectile insufficiency.

PMID- 9248804
TI  - Dynamic fast-gradient echo MR imaging of pancreatic tumours.
AB  - The purpose of this study was to determine the diagnostic utility of dynamic
      magnetic resonance imaging (MRI) of the pancreas. Twenty-eight adult patients
      with known or suspected pancreatic tumours were examined. Pre- and post
      gadolinium (GdDTPA-BMA) scans were obtained in combination with an oral negative
      contrast medium (ferristene) to mark the gastrointestinal tract. In 6 cases a
      more precise diagnosis could be made by dynamic MRI compared to unenhanced MRI.
      Surgery could confirm the MR diagnosis based on contrast enhancement in 83%
      compared to 78% for CT. The results of signal intensity (SI) measurements show
      that a combination of differences in baseline values before enhancement and the
      slope of enhancement within the first 20 s is a reliable criterion to distinguish
      between normal pancreas and hypovascular tumours. These tumours already show
      lower SI values before as well as lower slopes after early enhancement. Mainly
      two effects facilitate the final MRI diagnosis: (1) the delineation of the
      pancreas from the duodenum by the negative contrast medium, and (2) the
      enhancement pattern of pancreatic tumours by gadolinium-enhanced dynamic MRI
      compared to normal tissue within the early enhancement after contrast injection.

PMID- 9248805
TI  - Identifying and evaluating urinary incontinence in a female population.

PMID- 9248806
TI  - Prevalence and natural history of female incontinence.
AB  - OBJECTIVE: Urinary incontinence is a common and highly embarrassing condition
      among females of all age groups and has been the subject of several
      epidemiological studies in the past. METHODS: From an extensive literature search
      covering the time period from 1954 to 1995, 48 epidemiological studies and
      several other publications dealing with prevalence and natural history of female
      incontinence were reviewed. Meta-analysis of reported data was performed in
      respect of incontinence definitions, investigation methods, home country of
      survey and age groups. RESULTS: Available data are nonhomogenous and difficult to
      compare because of differences in definitions of incontinence, target populations
      and study design in different investigations. By grouping the studies by
      similarities in the above criteria and analysing the results for each group of
      studies, an attempt was made to understand the great variation of reported
      results. Differences in prevalence of incontinence were identified for all
      examined aspects and for distinct ethnic populations. The little information that
      exists on the incidence, spontaneous remission rates and risk factors were used
      to elucidate the natural history of female incontinence. CONCLUSION: A generally
      accepted definition of incontinence is highly desirable and should comprise
      aspects of severity and demonstrability of the condition, bother factor and
      impact on quality of life. Furthermore, basic requirements for epidemiological
      surveys of incontinence such as validation of questionnaire results need to be
      defined and standardised to establish a sensible basis for useful epidemiological
      studies in the future.

PMID- 9248807
TI  - The 'costs' of urinary incontinence.
AB  - Urinary incontinence is a prevalent and costly health condition. This paper
      discusses the 'costs' of untreated urinary incontinence. Costs are broadly
      conceptualised within a framework which includes physical, psychosocial, and
      economical components. Limited data is available documenting the different costs
      of incontinence. Further research is needed to better quantify these costs to aid
      clinicians, payers, and public policy-makers in decision-making related to
      incontinence management.

PMID- 9248808
TI  - Female urinary incontinence--symptom evaluation and diagnosis.
AB  - The assessment of female urinary incontinence aims to evaluate the severity of
      the patient's condition and its impact on her quality of life. The initial
      evaluation should include investigation of the patient's symptoms, the
      compilation of a frequency/volume chart, physical examination and urinalysis.
      Concurrent confounding conditions should be addressed. For effective treatment,
      it is necessary to differentiate between urge incontinence secondary to detrusor
      instability and stress incontinence due to sphincter weakness. Symptom assessment
      alone, performed clinically or by questionnaire, is diagnostically inaccurate and
      urodynamic diagnosis is necessary before invasive treatment. Self-reporting of
      symptom severity does correlate reasonably with objective measures of fluid loss,
      although standardised methods for the quantification of incontinence should be
      developed to allow comparisons between patients and the monitoring of disease
      progression and outcome. Symptom severity does not correspond to patients'
      perception of the effect of the condition on quality of life and this is an
      important factor in identifying what treatment is appropriate.

PMID- 9248809
TI  - Assessing the impact of urinary incontinence in a female population.
AB  - Urinary incontinence (UI) is a symptom. Patients seeking medical attention do so
      because of this symptom. As individuals' views of bothersomeness vary
      significantly, the objective degree of symptom severity is less important than
      the patient's overall outlook. Assessing well-being can be done by symptom
      evaluation, and general or condition-specific health-related quality of life
      questionnaire (HRQOL). Several studies using HRQOL questionnaires documented the
      negative effects of UI on the patient's well-being, especially on daily
      activities and psychological distress. Generalised HRQOL instruments can be used
      but they may lack sensitivity to the characteristics of incontinence and its
      impact. Recently condition-specific UI questionnaires have been developed for a
      better assessment of specific issues and a greater sensitivity to changes after
      treatments. They reveal a substantial impact on everyday life, but a poor
      correlation was observed between the objective and subjective measurements. More
      useful short-form versions have recently been developed that meet many of the
      needs of therapists.

PMID- 9248810
TI  - Promoting continence as a health issue.
AB  - Urinary incontinence is a common condition affecting hundreds of millions of
      people worldwide but for which up to 70% of sufferers seek no help. Continence
      promotion activities must target not only the incontinence sufferers and their
      families but also the general community, health professionals, the industry that
      manufactures continence products and drugs, and the Government which is
      responsible for funding directly or indirectly various programmes. Continence
      promotion programmes must therefore be sufficiently flexible to target these
      groups about what incontinence is, what can be done about it, and where to get
      help, and most importantly to de-stigmatise this condition. Continence promotion
      is taking place internationally through the efforts of the International
      Continence Society and locally through various national non-profit-making
      organisations. Activities include public awareness and professional education
      programmes; continence prevention strategies; and establishing mechanisms for
      improved communication. 'CONTInet', a dedicated Internet facility, is evolving as
      a major tool to achieve many of these goals.

PMID- 9248811
TI  - Benign prostatic hyperplasia: natural evolution versus medical treatment.
AB  - The epidemiology and natural evolution of benign prostatic hyperplasia (BPH) are
      important when considering the topic of natural evolution versus medical
      treatment. The incidence of BPH increases with age; it is thought that about 75%
      of men over 50 years of age suffer from some symptoms commonly associated with
      BPH. There are also differences in the incidence of BPH between various racial
      and ethnic groups. For example, it is considerably less common amongst Japanese
      men compared with Caucasians. Evidence from prospective studies, retrospective
      studies and the placebo arms of randomised, controlled studies regarding the
      natural evolution of BPH suggests that a strategy of 'watchful waiting' may be
      considered as a treatment option as the majority of patients do not show a
      worsening of symptoms over time. However, the chance for improvement of symptoms
      and the degree of symptom improvement has been shown to be higher with alpha 1
      blocker therapy than with 'watchful waiting'. As both symptoms and treatment have
      an impact on the patient's quality of life, there is now a strong case for
      involving the patient in making quality-of-life decisions based on his own
      preferences and attitudes.

PMID- 9248812
TI  - Evaluation of benign prostatic hyperplasia treatments: how can we improve the
      outcome measures and success criteria?
AB  - Treatment evaluation in benign prostatic hyperplasia (BPH) is complicated by a
      number of interdependent factors. The evaluation of the individual patient is
      influenced by the risk:benefit ratio and health related quality of life and this,
      in turn, is interrelated with the evaluation of therapeutic options. Current
      outcome measures include subjective measurements (e.g. symptom scores and patient
      reports) and objective measurements (e.g. uroflow and prostate volume). In order
      to improve outcome measures it is important to use health-related quality-of-life
      scales and symptom- and bother-associated scores. In addition, the patient should
      complete frequency and volume charts, and possibly use home flowmetry;
      transitional zone measurements may also play a role in finding a better treatment
      strategy. It is also important to consider the adverse effects and complication
      rates of invasive and pharmacological treatments (including their influence on
      quality of life) and economic factors such as the cost of treatment, the cost of
      following guidelines and the durability and failure rate associated with
      treatment. In order to manage the increasing number of BPH patients who seek care
      effectively it is important to share care with the GPs, but this will require
      improved guidelines, better data and better outcome measurements.

PMID- 9248813
TI  - Updated patient information for treatment of benign prostatic hyperplasia: a
      permanent challenge.
AB  - Ideally, a decision analysis should be performed in order to provide patient
      information and enhance decision-making procedures in benign prostatic
      hyperplasia (BPH). The steps associated with a decision analysis include creating
      a decision tree, identifying decision alternatives, quantifying the potential
      outcomes and weighing the potential outcomes according to the patients'
      requirements. However, doctors have their own individual experience and
      information on treatment from a wide variety of sources e.g. journals,
      conferences, the industry etc. Patients, in contrast, are informed by the popular
      media, friends and relatives etc. Updated patient information for the treatment
      of BPH therefore remains a permanent challenge. Each patient also has an
      individual acceptance of his symptoms, an individual tolerance to therapy
      according to his performance status, and an individual approach to medication or
      to surgery, whilst the doctor has novel experience with new drugs and
      instrumental procedures, his own individual availability of treatment options,
      and must always take the cost-effectiveness of a treatment into consideration.

PMID- 9248814
TI  - Using a large clinical database to assess the effectiveness of alfuzosin.
AB  - Treatment utility can be defined as a combination of objective clinical efficacy
      and quality-of-life results (i.e. subjective criteria). It is a particularly
      useful concept in diseases such as benign prostatic hyperplasia where important
      differences may exist between the results of objective measurements and the
      assessment of subjective complaints and quality-of-life impairment. The
      collection of data regarding treatment utility involves the generation of large
      patient care databases which provide long-term data in representative, general
      practice, patient populations. Such data provide overall information for
      physicians, health care providers, patients, insurance companies and health care
      decision-makers and enable them to define the long-term effectiveness of each
      treatment. In addition, predictive or risk factors which may assist in
      appropriate clinical decision-making may be identified. Such data also provide
      cost/ utility information. Finally, the data could be used in daily practice to
      allow the physician to make rapid therapeutic decisions.

PMID- 9248815
TI  - The importance of standardisation and validation of symptom scores and quality of
      life: the urologist's point of view.
AB  - Measurement of lower urinary tract symptoms in patients with benign prostatic
      hyperplasia (BPH) is extremely important as it is these symptoms which account
      for much of the morbidity associated with this disease. The symptoms of BPH
      interfere with factors affecting the patient's health status and quality of life
      and it is therefore important that uniform and consistent measures are available
      in order to compare patients and to facilitate monitoring of disease progression.
      A variety of tools are available to measure lower urinary tract symptoms, perhaps
      the best known being the International Prostate Symptom Score. It is also
      important to determine the degree of bothersomeness of symptoms and there are a
      number of disease-specific and generic instruments currently available for
      measuring the patient's quality of life. In conclusion, when treating BPH, the
      goal is to decrease symptoms and, in the process, quality of life will almost
      certainly be improved.

PMID- 9248816
TI  - Cultural and linguistic validation of questionnaires for use in international
      studies: the nine-item BPH-specific quality-of-life scale.
AB  - Questionnaires to evaluate symptoms and quality of life are being increasingly
      used in urology. It is, however, important that these questionnaires show
      equivalence when they are used in international, collaborative studies. Precise
      linguistic and cultural validation should greatly increase their compatibility in
      different population and cultural groups. Indeed, recent progress in the
      validation of symptom scores, such as the International Prostate Symptom Score (I
      PSS), has helped international comparability in epidemiology and clinical trials.
      The management of benign prostatic hyperplasia (BPH) increasingly focuses on
      quality of life and the development of a successful BPH-specific quality-of-life
      questionnaire is an important advance in the study of BPH. The nine-item BPH
      specific quality-of-life scale is currently undergoing linguistic and cultural
      validation and appears to be satisfactory for extensive use in different
      cultures.

PMID- 9248817
TI  - Role of age, education, and gender on cognitive performance in the Framingham
      Heart Study: community-based norms.
AB  - Normative data are presented for a neuropsychological test battery (Kaplan
      Albert) consisting of subtests from the original Wechsler Adult Intelligence and
      Memory Scales and the Benton and Hamsher Aphasia Examination. Analyses were based
      on archival data resulting from administration (1976-1978) of the battery to
      community residents participating in the Framingham Heart Study, a prospective,
      longitudinal study of cardiovascular risk factors. Using 3 age groups (55-64, 65
      74, and 75-88 years) and 4 education levels (5-8, 9-11, 12, > 12 years),
      individuals were stratified by age, gender, and education. Multiple linear
      regression analysis was used to relate main effects (age, education, and gender)
      and interactions of these effects to 9 test scores and to 2 composite scores
      identified by factor analysis. The oldest participants who had the fewest years
      of formal education had the lowest performance levels, with lower levels of
      performance for men than women in this least educated elderly cohort.

PMID- 9248818
TI  - Taking charge of remembering: locus of control and older adults' memory for
      speech.
AB  - The relation between control beliefs and recall of spoken word lists and prose
      passages was assessed for 32 older adults, ages 62 to 85, in a task where they
      were given control over presentation of stimuli. They differed in the degree to
      which they believed that factors within their control (internals) or outside
      their control (externals) affected their intellectual functioning; they were
      similar in age, education, vocabulary, and digit span. They were required to stop
      the speech input at points of their own choosing to recall the stimuli on a
      segment-by-segment basis. Externals were more likely than internals to make
      inaccurate predictions of the number of words they could remember and to choose
      longer segments than they could recall. Results suggest that externals are poorer
      than internals in monitoring on-line memory processing.

PMID- 9248819
TI  - Age differences in performance awareness on a complex financial decision-making
      task.
AB  - Individuals tend to be overconfident when making retrospective judgments about
      the quality of their decisions. However, few studies have focused on age
      differences in estimates of decision quality. In the present experiment
      performance estimates were provided by task-trained and untrained young and old
      individuals following completion of a series of complex financial decisions.
      Confidence levels were assessed by examining discrepancies between perceived and
      actual solution quality. Performance estimates of all 4 groups contained
      appreciable estimation error; however, no group showed a substantial directional
      bias toward underconfidence or overconfidence. Young trainees were significantly
      less confident in the quality of their decisions than young novices, but a
      comparable training effect was not found among older individuals. One's knowledge
      of the task, prior decision-making experience, and level of self-esteem may
      combine to determine the accuracy of one's retrospective performance estimates.

PMID- 9248820
TI  - Effectiveness of the number-consonant mnemonic for retention of numeric material
      in community-dwelling older adults.
AB  - The effectiveness of the number-consonant mnemonic for immediate recall and long
      term retention of 4 6-digit lock combinations was examined in 36 volunteers who
      were 60 years old or more. Participants were randomized into either an
      experimental condition (n = 17) that received training in the number-consonant
      mnemonic or a group that received placebo training only (n = 19). There were no
      differences between groups for number recall at posttest. At 3 days a modest
      difference appeared, favoring the experimental condition, which became highly
      significant at the 7-day telephone follow-up. This finding suggests that a
      distinguishing characteristic of the number-consonant mnemonic may be the extent
      to which it facilitates the maintenance of learned numeric material in memory
      over time.

PMID- 9248821
TI  - Memory scores in middle-aged rats predict later deficits in memory, paradoxical
      sleep, and blood glucose regulation in old age.
AB  - Age-related deficits in memory are correlated with deficits in paradoxical sleep
      and poor glucose tolerance in rats. The present experiment used a longitudinal
      design to determine whether memory or glucose tolerance in middle-aged rats could
      predict deficits in memory, sleep, and glucose tolerance in old age. Correlations
      were obtained between spontaneous alternation scores and glucose tolerance levels
      in middle age (14 months) and inhibitory avoidance, daytime sleep, and glucose
      tolerance levels in old age (24 months). Spontaneous alternation scores, but not
      glucose tolerance levels, predicted performance on all 3 behavioral and
      biological measures in old age. Measures of functional integrity, such as memory,
      may be sensitive predictors of subsequent age-related change in specific
      cognitive and neurobiological systems.

PMID- 9248822
TI  - Decentering therapy: textual analysis of a narrative therapy session.
AB  - Postmodern models of therapy stress the participation of the clinician in a
      nonhierarchical, non-objectifying role, and highlight the therapist's
      embeddedness in the same processes of social construction as are the individual
      and the family. While much theory has been published in recent years, the actual
      conduct of a therapy session derived from the premises of postmodernism remains
      unclear. We investigated how a postmodern therapist manages talk in an actual
      session. We used textual analysis to examine a couples therapy session conducted
      by a prominent narrative therapist. Analysis of the talk led to descriptions of
      the couple's and therapist's agenda, and their interaction. The therapist's
      agenda is described in terms of "decentering" both the local unfolding narrative
      and its embeddedness in larger cultural stories. Five conversational practices:
      matching/self-disclosure, reciprocal editing, turn management to deobjectify,
      expansion questions, and reversals are examined. These practices inform the
      deployment of a decentering agenda in this specific text.

PMID- 9248823
TI  - Mapping and/or discovering meaning in family therapy: an e-mail conversation.

PMID- 9248824
TI  - Treating inner-city families of homicide victims: a contextually oriented
      approach.
AB  - Violence, including youth homicide, has assumed near epidemic proportions in US
      inner cities, with few signs that such violence is abating. Professionals working
      with families after the murder of a family member, are faced with the task of
      helping such families achieve a meaningful restoration of functioning. At the
      same time, there is a need to prevent retaliatory violence by surviving siblings
      and other family members. A treatment model will be discussed that uses the
      basic, theoretical principles of Boszormenyi-Nagy's Contextual Therapy (CT) while
      incorporating White and Epston's technique of "therapeutic certificates" in work
      with young people coping with loss via homicide. Case examples, drawn from the
      author's work at a unique, predominantly African American agency in an urban
      inner city will be used to illustrate applications of CT principles, and to show
      how therapeutic certificates can provide tools to clinicians working with this
      deeply troubling problem.

PMID- 9248825
TI  - Believing in make-believe: looking at theater as a metaphor for psychotherapy.
AB  - In this essay, I explore the theatrical dimensions of psychotherapy. I argue that
      many of the historical, practice-related, and conceptual connections between
      theater and therapy often are only alluded to in the literature, but rarely made
      explicit. In doing so, however, it seems apparent that, as a metaphor for
      psychotherapy, theater perhaps offers a more appropriate fit than those narrative
      and conversational metaphors that have been employed so far. Proposing that
      theater is, in fact, the metaphor on which psychotherapy bases itself, I briefly
      examine some of its implications for how therapy might be conceptualized and
      performed. I conclude by inviting other therapists to consider--by openly
      acknowledging theater as a metaphor for psychotherapy--if they might then become
      more engaging, creative, and imaginative in their work.

PMID- 9248826
TI  - The significance of romantic love for marriage.
AB  - In this study, 605 subjects were asked about romantic love and marriage. Married
      people differentiated themselves from single people with stable partners and
      divorced people with new partners by more frequently living together with their
      great love, more reciprocity in that love, and less disappointments in love
      relationships prior to the current relationship; but they also described
      themselves as less happy and satisfied than the single and divorced respondents,
      particularly with regard to tenderness, sex, and conversation with their
      partners. Independent of marital status, those who were greatly in love with
      their partners describe themselves as happier. Love at first sight, relative to a
      gradually developing love, nevertheless, did not have a worse prognosis for
      happiness in marriage. Being in love seems to be of greater importance for the
      prognosis of the marriage than marital happiness and satisfaction.

PMID- 9248827
TI  - Overt and covert coparenting processes in the family.
AB  - This article introduces a new self-report instrument designed to measure the
      frequency of parental behaviors thought to promote or undermine children's sense
      of family. Members of 103 married couples rated their behavior in both public
      (all family members present) and private (alone with child) contexts. Factor
      analyses of these data revealed four distinct factors indexing: behaviors in the
      service of promoting a sense of Family Integrity, largely covert parent-to-child
      communications undermining, or conveying Disparagement of, the coparental
      partner; overt interparental Conflict in the presence of the child; and
      coparental disciplinary activities (Reprimand). Significant husband-wife
      correlations were found on each of the four individual subscales. Construct
      specific intercorrelations also obtained between like scales on the new measure
      and on the Family Environment Scale and Quality of Coparenting Scale. Cluster
      analyses of husbands' and wives' scores on the four Coparenting Scale factors
      suggested five "types" of coparenting families: Disconnected, Supportive,
      Average, Distressed-Conflicted, and Passionate. These clusters, along with the
      value of self-report instruments in assessing coparenting behaviors that may be
      largely clandestine in nature, are discussed.

PMID- 9248828
TI  - Family climate and expressed emotion in the course of alcoholism.
AB  - Family-based predictors of relapse were examined in 100 alcoholics who
      participated in a 12-week treatment program with 6-month and 18-month followups.
      "Expressed Emotion" (EE), or attitudes of relatives toward the alcoholic as
      measured by the Camberwell Family Interview, scales measuring rejection of the
      alcoholic by relatives, and self-reports of partner interaction were evaluated as
      possible predictors of abstinence. During therapy, partnership interactions
      showed a transient deterioration with increased temporary friction. Based on
      conservative criteria, the abstinence rate was 40% at 6-month followup and 30% at
      18-month followup. An association with the relapse at followup could be obtained
      for the Patient Rejection Scale (PRS) and, using empirically derived
      classification rules, for the main three variables of the Camberwell Family
      Interview (CFI) conducted on admission: "Critical Comments," "Emotional
      Overinvolvement," and "Warmth." A low number of Critical Comments and a high
      score in Warmth were associated with a lower risk of relapse; however, contrary
      to expectations, Emotional Overinvolvement of the significant other was
      associated with more abstinence. In addition, the number of Critical Comments
      made by relatives about the alcoholic, a major component of high EE as measured
      by the CFI, had a statistically significant impact on the "survival function" of
      abstinence, and thus contributed to the prediction of the course of alcoholism in
      the expected direction.

PMID- 9248829
TI  - Biochemical and structural approach to collagen synthesis under electric fields.
AB  - The effects of electric fields of different intensities and directions on the
      collagen synthesis of guinea pigs was studied. The effects of vertical and
      horizontal electric fields of 1.9 kV/m and 0.9 kV/m, generated with voltages of
      300 V and 150 V DC, respectively, on collagen synthesis, was evaluated by
      assessing the amount of hydroxyproline in the liver tissue, and by histological
      examination of tissue samples. The Stegemann-Stalder method was used to determine
      hydroxyproline content of the tissues. While the 0.9 kV/m vertical and horizontal
      electric fields substantially decreased the amount of hydroxyproline in the
      liver, the 1.9 kV/m electric fields in both directions increased the
      hydroxyproline content. The vertical electric field was more effective than the
      horizontal one both in the increases and the decreases. These findings were
      verified histologically.

PMID- 9248830
TI  - Electrostatic forces as a possible mechanism underlying skeletal muscle
      contraction.
AB  - A possible mechanism is put forward to explain the sliding of thin filaments
      during muscle contraction. In our model, repulsion due to electrostatic forces is
      the mechanism which triggers crossbridges to cause the thin filaments to slide.
      The mechanism proposed could operate regardless of whether the myosin heads
      rotate or bend, although recent experimental evidence seems to confirm the latter
      action. In spite of its simplicity, the model prediction of the velocity of
      sliding of the thin filaments agrees well with experimental values from in vitro
      motility assays.

PMID- 9248831
TI  - Fluorescence quenching studies of the rat ovarian LH/hCG receptor.
AB  - Fluorescence quenching method providing information about the structure and
      dynamics of proteins, ligand-protein and protein-lipid interactions was used in a
      study of the rat ovarian LH/hCG receptor. The efficiency of two different
      quenchers, acrylamide and iodide, was tested. Acrylamide was significantly more
      effective in quenching of intrinsic fluorescence of ovarian membranes than iodide
      and therefore it was used in all of the following experiments. Both acrylamide
      and iodide were not effective in quenching of membranes labelled with
      fluorescence probe 1,6-diphenyl-1,3,5-hexatriene (DPH). In the process of
      desensitization of ovarian LH/hCG receptors the administration to rats of hCG
      modified the quenching rate of protein fluorescence and intrinsic fluorescence
      spectral properties of membranes. Alteration in the quenching of intrinsic
      fluorescence of ovarian membranes was observed after chemical modification of
      LH/hCG receptors by 2-hydroxy-5-nitrobenzyl bromide (HNB-Br). The accessibility
      of tryptophan fluorophores was increased in HNB-Br-treated membranes.
      Delipidation of the LH/hCG receptor modified the quenching of protein
      fluorescence characteristic for control proteoliposomes. These results
      demonstrate that fluorescence quenching technique can be successfully applied in
      the study of the LH/hCG receptor.

PMID- 9248832
TI  - Oxidation of low density lipoproteins leads to disturbance of their binding with
      alpha-tocopherol.
AB  - The dynamics of binding of exogenous alpha-tocopherol (alpha-T) added to native
      or oxidatively modified LDLs (LDLs or oxLDLs) were investigated. Venous blood
      from 31 clinically healthy blood donors (15 males and 16 females) was used. LDLs
      were isolated by density gradient ultracentrifugation. LDLs were oxidized in
      vitro by CuSO4. LDLs or oxLDLs were enriched with exogenous alpha-T (initial
      concentrations: 0; 10; 20; 50; or 100 nmol per mg protein). The contents of alpha
      T in LDLs or in oxLDLs were measured by HPLC. Lag-phase of LDL oxidation before
      or after saturation with alpha-T was recorded. Correlation analysis of the lag
      phase of LDL oxidation and alpha-T content in LDLs was carried out by the method
      of Esterbauer et al. The experimental results demonstrated that: (i) alpha-T was
      incorporated into native LDLs to a higher extent as compared to oxLDLs. (ii) A
      saturation of LDLs and oxLDLs with alpha-T was observed. (iii) A positive
      correlation was observed between the duration of the lag-phase of LDL oxidation
      in vitro and the content of alpha-T in LDLs. (iv) Based on LDL saturation with
      alpha-T, the persons could be classified in two groups: LDLs from group I of 26
      persons were found to incorporate exogenous alpha-T to the extent of 1.8 to 3
      times its initial concentration; LDLs from group II of 5 persons incorporated
      little or no exogenous alpha-T. In the first group, oxidation of LDLs lead to a
      considerable decrease in alpha-T dependent variable k and to a moderate reduction
      of alpha-T-independent variable alpha in the equation of Esterbauer et al.: lag
      phase = k.[alpha-tocopherol]+alpha. In the second group, oxidation of LDLs lead
      to insignificant changes in k, as well as in a. (v) According to the levels of k
      and a the native LDLs from the second group of 5 persons were very close to
      oxLDLs from the first group of 26 persons. Presumably, native LDLs from the
      second group of persons were initially oxidatively modified, and probably this
      will be a risk group in relation to atherogenic disorders.

PMID- 9248833
TI  - Involvement of plasma membrane redox system in the generation of trans-root
      electrical potential difference in excised maize root.
AB  - Possible involvement of the plasma membrane bound redox system in the generation
      of the trans-root electrical potential difference (TRP) arising across 8 day old
      maize (Zea mays L. hybrid ZPSC704) roots was studied. Excised roots were exposed
      to artificial impermeable electron acceptors (potassium hexacyanoferrate III and
      potassium hexachloroiridate IV) in external solution, and TRP response, oxygen
      consumption rate, proton efflux and reduction of the electron acceptors were
      analyzed. The effect of hexacyanoferrate III (HCF III) was tested at three
      concentrations (0.1; 0.5 and 1.0 mmol/l), and hexachloroiridate IV (HCI IV) in
      the concentration range 10(-7)-5.10(-4) mol/l. Both electron acceptors
      depolarized the trans-root potential, an order of magnitude lower concentrations
      of hexachloroiridate producing a much more rapid depolarization of greater
      magnitude. The roots had a higher capacity to reduce 0.1 mmol/l hexachloroiridate
      than 1 mmol/l hexacyanoferrate. Also, an increased level of acidification induced
      by HCI IV than HCF III could be observed. The rate of oxygen consumption showed
      an increase of about 20% in both cases. These results prove that electron
      transplasma membrane transport process(es) contribute to the total trans-root
      electrical potential difference across an excised maize root.

PMID- 9248834
TI  - Human polymorphonuclear leukocytes: effect of chloroquine on aggregation,
      arachidonic acid liberation and thromboxane B2 generation.
AB  - The effects of the antimalarial drug chloroquine (CQ) on arachidonic acid (AA)
      liberation from, thromboxane B2 (TXB2) formation in, and aggregation of isolated
      human polymorphonuclear (PMN) leukocytes stimulated with N-formyl-methionyl
      leucyl-phenyl-alanine (FMLP) were investigated. CQ decreased aggregation of
      stimulated PMN leukocytes, however in contrast to AA liberation and TXB2
      formation, lower concentrations were more effective than the highest one used.
      This effect may be associated with an increase in intracellular pH, reported to
      be induced by higher CQ concentrations, possibly counteracting the inhibition of
      aggregation, and/or eliminating negative feed back control of aggregation by lack
      of prostaglandins.

PMID- 9248835
TI  - Histopathologic and electron-microscopic features of corneal and scleral collagen
      fibers in osteogenesis imperfecta type III.
AB  - BACKGROUND: This report describes the histopathologic and electron-microscopic
      features of an eye from a patient with osteogenesis imperfecta type III. In
      particular, the diameters of corneal stromal and scleral collagen fibers were
      determined. METHODS: The eyes of an 18-year-old white male with osteogenesis
      imperfecta type III were examined by light and electron microscopy and the
      pathological features were compared with an age-matched control eye. RESULTS: The
      cornea was clear. The sclera had a blue color and was moderately thinned,
      especially at the equator. Light microscopy revealed absence of Bowman's layer.
      Transmission electron microscopy confirmed complete absence of Bowman's layer
      without evidence of scarring or inflammation. The collagen fibers of the corneal
      stromal lamellae were about 25% narrower than in the control, but the cornea was
      otherwise unremarkable ultrastructurally. The collagen fibers of the sclera were
      approximately 50% narrower than in the control and were much more uniform in
      size. Prominent portions of elastic fibers, which are usually only present in a
      small number in the inner portion of the sclera, were present throughout the
      sclera. CONCLUSION: We propose that it is the uniformity of the scleral collagen
      fibers which gives the sclera translucence, producing the blue color often
      observed clinically in osteogenesis imperfecta. Absence of Bowman's layer of the
      cornea did not interfere with the stability of the cornea in this case. This
      appears to be the first published pathological examination of the eye in
      osteogenesis imperfecta type III.

PMID- 9248836
TI  - An immunocytochemical study of isolated human retinal Muller cells in culture.
AB  - BACKGROUND: We report a modified method for the isolation and propagation of
      adult human Muller cells in culture. METHODS: The retina of postmortem human eyes
      was mechanically dissociated and cultured. Using immunocytochemical techniques,
      these cells were stained with monoclonal antibodies specific for Muller cells,
      glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase (GS) and
      keratin. Transmission electron microscopy (TEM) was also performed. RESULTS: The
      dissociated and cultured cells expressed vimentin and GS, but not GFAP. At least
      85% of these cells stained with a Muller cell-specific monoclonal antibody. Using
      TEM, flat cells containing 13-nm intermediate filaments and glycogen were
      identified. CONCLUSION: Human retinal Muller cells can be isolated and propagated
      in culture. Purified cell cultures are required for controlled studies of the
      normal physiology and pathologic responses of Muller cells.

PMID- 9248837
TI  - Large-field S-cone flicker test.
AB  - BACKGROUND: Disturbances of blue color vision and of temporal contrast
      sensitivity can indicate early damage in glaucoma. For the present study a quick
      and easy test was devised which examines both functions at one time by testing
      the temporal contrast sensitivity of a blue flickering light on an intense yellow
      background. METHODS: Large coextensive background and test fields (85 degrees)
      are used, making fixation uncritical. Detailed experiments were made in two
      normal subjects to derive spectral sensitivity curves from flicker-fusion
      frequency (FFF) versus intensity functions and to obtain complete temporal
      contrast-sensitivity (De Lange) curves under different levels of adaptation and
      test lights. After selection of appropriate luminances and one stimulation
      frequency from these experiments, test-retest variability was studied in four
      subjects in five repetitions. In addition, normal values were collected from 22
      subjects. RESULTS: Spectral sensitivities for two levels of FFF (15 Hz and 44 Hz)
      agree with Stiles' pi 1 at the low and with pi 4 at the high FFF. Temporal
      contrast-sensitivity curves show a low-frequency section with peak sensitivity at
      1 Hz and a high-frequency section with a peak at around 4 Hz. From the basic
      experiments the following conditions for the clinical examination were selected:
      Background luminance 2600 cd/m2, test luminance at 451 nm 0.8 cd/m2, stimulation
      frequency 4 Hz. The test-retest variability showed an acceptable intraclass
      correlation co-efficient (0.6). CONCLUSIONS: The present experiments carried out
      with a very large stimulus led to meaningful results which are in rather good
      agreement with results reported in the literature on small-field stimuli. The
      blue-on-yellow flicker test carried out under the conditions mentioned above is a
      quick and easy test which could be helpful in improving early glaucoma diagnosis.

PMID- 9248838
TI  - Ultrasound biomicroscopic analysis of the effect of pilocarpine on the anterior
      chamber angle.
AB  - BACKGROUND: This study was carried out to determine the effects of pilocarpine on
      the anterior chamber angle in healthy volunteers. METHODS: We measured changes in
      anterior chamber depth (ACD), trabecular-iris angle (TIA), angle opening distance
      at 250 and 500 microns from the scleral spur (AOD250 and AOD500), and iris
      thickness using ultrasound biomicroscopy in 48 eyes of 48 normal volunteers (ages
      18-57 years, mean 34.8 years) before and 1 h after instillation of 2%
      pilocarpine. RESULTS: Pilocarpine altered the TIA by -18.6 degrees to +10.5
      degrees (mean -4.16 degrees), and change in the TIA increased significantly and
      linearly in relation with decrease in the pretreatment TIA (r = 0.929).
      Pilocarpine altered AOD250 change by -136 to +94 microns (mean -38 microns) and
      AOD500 by -151 to +157 microns (mean -42 microns); changes in the AOD250 and
      AOD500 were significantly correlated to the pretreatment AOD250 and AOD500
      values, respectively (r = 0.923 and r = 0.896, respectively). The pilocarpine
      induced change in the ACD showed a linear relationship to the pretreatment ACD (r
      = 0.887). The changes in the TIA, AOD250 and AOD500 showed greater increases in
      association with lower pretreatment ACD (r = 0.848, r = 0.891, r = 0.842) and
      smaller change in the ACD (r = 0.834, r = 0.839, r = 0.812). CONCLUSIONS: The
      response of the anterior chamber angle to pilocarpine, narrowing or widening,
      depended on its pretreatment state. The ability to predict the pilocarpine
      induced change in the angle before the instillation of pilocarpine would be
      helpful in treating patients with glaucoma.

PMID- 9248839
TI  - Diagnosis of intraocular lymphoma by polymerase chain reaction.
AB  - BACKGROUND: Cytopathological examinations have been used in the diagnosis of
      intraocular lymphoma. However, sometimes it is not easy to detect malignant cells
      in the biopsy specimens. We applied a method that identified monoclonal
      proliferation of B lymphocytes by using polymerase chain reaction (PCR) in the
      diagnosis of patients suspected to have intraocular B-cell lymphoma. METHODS:
      Three specimens of the diagnostic vitrectomy were studied by cytological
      examination and by PCR to amplify the complementary determining region (CDR3) of
      immunoglobulin heavy chain (IgH) gene. As a positive control, a biopsy specimen
      of an orbital lymphoma was examined; four vitrectomy specimens from patients with
      diabetic retinopathy, proliferative vitreo-retinopathy, acute retinal necrosis
      (ARN) and macular hole were negative controls. RESULTS: On cytologic examination,
      no malignant cells were found in three specimens: suspected intraocular lymphoma
      and one ARN. In contrast, a discrete band that reflected monoclonal proliferation
      of B lymphocytes was detected by PCR in specimens from two patients and the
      positive control. Vitrectomy specimens from the negative controls, including ARN,
      did not show a discrete band on PCR. CONCLUSIONS: Two cases of ocular malignant
      lymphoma were diagnosed by PCR identification of monoclonal proliferation of B
      lymphocytes. This method may be an additional diagnostic tool in the diagnosis of
      intraocular B-cell lymphoma.

PMID- 9248840
TI  - The effect of pregnancy on mild diabetic retinopathy.
AB  - PURPOSE: To study microaneurysm (MA) formation and disappearance rates during
      pregnancy and postpartum in diabetic women with mild diabetic retinopathy.
      METHODS: Red-free photographs were taken at the 12th, 24th and 32nd-36th weeks of
      pregnancy and 3 and 6 months postpartum from 21 type 1 diabetics with mild
      diabetic retinopathy. In a subset of 13 patients follow-up was continued until 1
      year after pregnancy. Fundus photographs were analysed using a computer-assisted
      fundus lesion localization system. RESULTS: In the whole material the total MA
      count was 3.1 +/- 3.6 (mean +/- SD) at the 12th week, 3.4 +/- 3.1 at the 24th
      week, 4.1 +/- 4.9 at the 32nd-36th week, 5.4 +/- 6.2 at 3 months postpartum and
      5.2 +/- 5.8 at 6 months postpartum. We found that MA count increased during
      pregnancy, but it was highest 3 months postpartum. Both the rate of MA formation
      and the rate of MA disappearance increased during pregnancy, with the
      disappearance rate exceeding the formation rate 6 months postpartum. In patients
      having mean HbA1c levels below the median value of 6.38 mmol/l there was a flare
      up of MAs during pregnancy, levelling by 3 months postpartum. Patients with a
      higher than the median (0.76 mmol/l) decrease in HbA1c level compared to pre
      pregnancy HbA1c also developed more MAs during the course of pregnancy.
      CONCLUSIONS: These data suggest that there is continuous turnover of MAs during
      pregnancy. MA count increases during pregnancy but the MA count was highest 3
      months postpartum, after which the formation rate started to decline. Temporary
      aggravation of mild retinopathy occurs in diabetic patients after normalization
      of blood glucose levels.

PMID- 9248841
TI  - Comparison of Snellen acuity and objective assessment using the spatial frequency
      sweep PVER.
AB  - BACKGROUND: We compared the vision objectively assessed by spatial frequency
      sweep pattern-reversal visual-evoked response (SPVER) with the Snellen acuity in
      patients. METHODS: SPVER acuity and Snellen acuity were measured in 100 patients
      with various ocular pathologies, including macular diseases, diffuse retinal
      degeneration, optic nerve diseases, glaucoma, and high myopia. For SPVER, 10
      sinusoidally modulated vertical gratings were presented as stimuli. The responses
      were averaged and displayed through the discrete Fourier transform on the monitor
      display. The PVER acuity was determined by extrapolating the SPVER amplitude
      spatial frequency function to baseline. RESULTS: Vision ranged from 20/15 to
      20/400 with Snellen acuity, and from 20/25 to 20/190 with SPVER. The overall
      correlation between the two acuities was r = 0.666. The correlation varied from r
      = 0.895 in eyes with glaucoma to r = 0.436 in eyes with optic nerve disease.
      Seventy-seven eyes (77%) had a visual acuity agreement of within 1.0 octave
      between the two measurements. CONCLUSION: The SPVER acuity and the Snellen acuity
      correlated to a certain degree. Discrepancies were found in certain diseases,
      with the highest disparity in patients with optic nerve disease. We conclude that
      the SPVER is effective in estimating vision objectively, particularly in patients
      in whom the standard Snellen test is impossible to perform or yields unreliable
      results.

PMID- 9248842
TI  - Actinomyces infection in porous polyethylene orbital implant.
AB  - BACKGROUND: A 60-year-old patient developed actinomycotic inflammation within a
      porous polyethylene orbital implant which she received following enucleation.
      METHODS: She had repeated conjunctival exposures with inflammation; the primary
      implant was removed and replaced with another one. RESULTS: The anterior two
      thirds of the porous implant was infiltrated with numerous actinomycotic granules
      surrounded by polymorphonuclear cells and necrotic debris. The organisms were
      demonstrated with Gram stains on the histopathologic preparations and with
      scanning electron microscopy. Within the zones of inflammation, the polyethylene
      skeleton of the implant was extensively damaged. CONCLUSION: Actinomycetes have
      been described as causative organisms in conjunctivitis, blepharitis,
      canaliculitis, dacryocystitis and keratitis, but to the best of our knowledge
      actinomycotic involvement has never been reported in an infected porous orbital
      implant.

PMID- 9248843
TI  - Early conjunctival changes following treatment with metipranolol and
      preservatives are not reversible with dexamethasone.
AB  - BACKGROUND: Topical medication for the treatment of glaucoma alters the cellular
      and extracellular composition of the superficial and deep conjunctival layers. We
      sought to determine whether, after short-term use of metipranolol with
      preservatives, subsequent application of steroids or metipranolol without
      preservatives affects these conjunctival changes. METHODS: Rabbits received
      topical metipranolol over a period of 6 months. For the following 2 months, one
      group received metipranolol without preservatives, and another group steroids.
      For controls, animals were treated with preservatives only or metipranolol with
      preservatives for 6 months. Superior bulbar conjunctiva was examined by light
      microscopy, immunohistochemistry, and transmission electron microscopy. RESULTS:
      On light microscopic and immunohistochemical examination of conjunctival
      specimens from all groups, there was an increase of subepithelial collagen
      deposition in all treated groups. Treatment with steroids or preservative-free
      metipranolol did not alter the initial effects. By electron microscopy,
      additional extracellular matrix changes were seen as well as degenerative changes
      of tissue fibroblasts. CONCLUSION: The animal model used was able reliably to
      produce conjunctival changes following antiglaucomatous therapy. The changes seen
      were early changes, because there was no increase of inflammatory cells. Steroids
      did not significantly affect the changes. The beneficial effect of steroids used
      prior to glaucoma surgery remains controversial.

PMID- 9248845
TI  - Magnetic resonance imaging of cyclodialysis clefts.
AB  - BACKGROUND: Our purpose was to determine whether cyclodialysis clefts can be
      imaged with magnetic resonance imaging (MRI). METHODS: Surgical cyclodialysis
      clefts extending approximately 3 clock hours were created in four New Zealand
      white rabbits. Eyes were scanned with an ocular MRI coil. Images obtained after
      intravenous gadolinium, topical godalinium, and gadolinium injected into the
      cleft were compared to images obtained without contrast. Two human eyes were also
      scanned for cyclodialysis clefts with MRI. RESULTS: Direct injection of
      gadolinium into the suprachoroid space yielded definitive localization and
      delineation of the cyclodialysis cleft. Cyclodialysis clefts could also be imaged
      following enhancement with topical or intravenous gadolinium. Without contrast
      medium, the clefts could not be clearly identified in rabbits. In a patient with
      hypotony and choroidal effusion following cataract surgery, a cyclodialysis cleft
      and enhancement of the suprachoroidal space were found with intravenous
      administration of gadolinium. MRI from a patient with a trabeculo-suprachoroidal
      shunt also demonstrated gadolinium enhancement of the suprachoroidal space.
      CONCLUSION: Cyclodialysis clefts can be imaged using gadolinium-enhanced MRI in
      rabbits and humans.

PMID- 9248844
TI  - Role of protein tyrosine phosphorylation in rat corneal neovascularization.
AB  - BACKGROUND: Recent studies have suggested that tyrosine kinase pathways that are
      activated by angiogenic growth factors may play a role in corneal
      neovascularization. METHODS: Corneal neovascularization was induced in rat
      corneas by chemical cauterization. At 6, 24, 48, 96, and 168 h after chemical
      cauterization the rat corneas without the corneal epithelium were prepared for
      gel electrophoresis. Total protein profiles of the corneal samples were examined
      by staining gels with Coomassie brilliant blue. Tyrosine-phosphorylated proteins,
      three angiogenic growth factors (basic fibroblast growth factor, vascular
      endothelial growth factor, and platelet-derived growth factor-B chain), and three
      intracellular signal proteins in the tyrosine kinase pathways (phospholipase C
      gamma, SHC, and mitogen-activated protein kinase) in the corneal samples were
      examined by western blot analysis. A topical treatment of genistein eye drop (5
      mg/ml) was used for inhibition of corneal neovascularization after chemical
      cauterization in rats. RESULTS: In total protein profiles, three bands in the
      corneal samples were increased after cauterization. Overall tyrosine
      phosphorylated proteins and all three angiogenic growth factors increased with
      progression of corneal neovascularization. The tyrosine-phosphorylated forms of
      three intracellular signal proteins were also increased after cauterization.
      Treatment with topical genistein was effective in inhibiting corneal
      neovascularization in rats. CONCLUSION: Protein tyrosine phosphorylation was
      involved in inflammation-induced corneal neovascularization. Tyrosine kinase
      inhibitors may have utility as inhibitors of corneal neovascularization.

PMID- 9248846
TI  - HLA-DR6 (possibly DRB1*1301) is associated with susceptibility to Takayasu
      arteritis in Mexicans.
AB  - Takayasu arteritis is characterized by a "pulseless" condition and occurs
      frequently in young females from Asian and South American countries. This disease
      has been found to be linked with major histocompatibility complex (MHC) antigens
      in Japanese individuals. In the present study we compared gene frequencies of
      class I, class II, and class III MHC genotypes in patients with Takayasu
      arteritis and ethnically matched healthy controls. Serological typing was
      confirmed by molecular typing at the DNA level. We found significant increases in
      the frequencies of human leucocyte antigen (HLA)-DR6 and HLA-B62 in patients
      compared to the healthy controls (P corrected [C] = 0.0007, relative risk [RR] =
      5.08; PC = 0.05, RR = 3.13 respectively). However, since the number of patients
      was considerably lower than the number of controls this can be considered as a
      tendency and not a true association. On the other hand, we found a significantly
      decreased frequency of HLA-DR4 in patients compared to healthy controls (PC =
      0.04, RR = 0.34). At the DNA level, all DR6-positive individuals were HLA
      DRB1*1301 whereas controls were HLA-DRB1*1301 (4.2%). Takayasu arteritis in
      Mexicans is probably associated with the HLA-DR6 (DRB1*1301) gene.

PMID- 9248847
TI  - The protective effect of D-sotalol against hypoxia-induced myocardial uncoupling.
AB  - The effects of D-sotalol on intercellular electrical coupling and ultrastructure
      under hypoxic conditions were investigated in myocardial samples from eight young
      (1-2 months) and four older (10-12 months) guinea pigs. A right ventricular
      muscle strip was kept simultaneously in two divided chambers and superfused with
      normoxic and/or hypoxic (97% N2+ 3% Co2) Krebs solution. Hypoxia caused
      shortening of action potential duration (APD) and electrical cell-to-cell
      uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30
      min), administration of 3.10(-7)M of D-sotalol to the hypoxic perfusate led to a
      recovery of electrical coupling. Transmission electron microscopy revealed
      moderate reversible ultrastructural alterations of the cardiomyocytes. No
      apparent changes in intercellular junctions were observed. The recoupling effect
      of sotalol decreased with the time of hypoxia as the ultrastructural damage
      progressed. After prolonged hypoxia (more than 30 min), cardiomyocytes were
      markedly injured, intercellular junctions were severely affected, and gap
      junctions occurred less frequently. In these cases, administration of D-sotalol
      caused only transient recoupling. After 1 h of hypoxia, no recoupling was
      observed. Pretreatment with D-sotalol prevented hypoxia-induced electrical
      uncoupling and markedly attenuated ultrastructural damage, although shortening of
      APD still persisted. Our results indicate that the cardioprotective effect of D
      sotalol on electrical intercellular coupling is closely associated with sotalol
      induced prevention of the ultrastructural damage. Considering previous results,
      we suggest that this protective effect of D-sotalol may be related to its ability
      to increase intracellular cyclic adenosine monophosphate and, thereby, to
      decrease cytosolic free Ca. These effects can explain the antiarrhythmic and
      defibrillating properties of D-sotalol.

PMID- 9248849
TI  - Improvement of left ventricular diastolic dysfunction in hypertensive patients 1
      month after ACE inhibition therapy: evaluation by ultrasonic automated boundary
      detection.
AB  - The purpose of this study was to detect any improvement in left ventricular
      diastolic dysfunction in hypertensive patients 1 month after cilazapril therapy.
      Twenty-three patients, 5 men and 18 women (mean age, 53.52 +/- 9.10 years), with
      mild or moderate hypertension (160 +/- 13/98 +/- 10 mm Hg), and free of other
      cardiac or systemic diseases, were studied using ultrasonic automated boundary
      detection (ABD) and pulsed Doppler echocardiography, before and 1 month after a
      daily dose of 2.5 mg of cilazapril. The following new ABD diastolic indices were
      determined: the time rate of area change in early diastole (dA/dt)E, that in late
      diastole (dA/dt)A, and their ratio (dA/dt)E/(dA/dt)A, while Doppler transmitral
      flow measurements of left ventricular diastolic filling were also simultaneously
      recorded. The ABD results showed left ventricular diastolic dysfunction (LVDD) in
      9 of 23 patients (39%) compared with the ABD values of 12 normal volunteers.
      Neither method revealed any significant difference before and after treatment in
      the patient group as a whole. However, in the group of 9 patients with diastolic
      dysfunction, the ABD ratio (dA/dt)E/(dA/dt)A was significantly improved after
      cilazapril therapy (1.20 +/- 0.21 versus 1.41 +/- 0.17; P < 0.05). We concluded
      that a large percentage (39%) of patients with mild or moderate hypertension had
      reduced diastolic performance of the left ventricle at a stage of the disease
      when systolic dysfunction and/or hypertrophy were not evident. Significant
      improvement of diastolic dysfunction in hypertensive patients could be detected
      by the proposed ABD new diastolic indices 1 month after cilazapril therapy. In
      conclusion, automatic boundary detection should be a useful non-invasive modality
      for the early diagnosis of left ventricular diastolic dysfunction, as well as
      early recognition of its improvement.

PMID- 9248848
TI  - Effects of pinacidil, verapamil, and heart rate on afterdepolarizations in the
      guinea-pig heart in vivo.
AB  - Recently, ionic current simulation in the Luo-Rudy model has elucidated putative
      mechanisms of afterdepolarizations under various experimental conditions. The
      present study was aimed at gaining insight into the differential mechanism of
      different types of afterdepolarizations in the guinea-pig heart in vivo. The
      effects of pharmacological and heart rate perturbations on early (EADs) and
      delayed (DADs) afterdepolarizations, induced by either digoxin, CsCl, or BayK
      8644 were studied, using mid-myocardial left ventricular monophasic action
      potential (MAP) recordings. Digoxin insignificantly shortened sinus cycle length
      (SCL) and CsCl and BayK 8644 differentially prolonged SCL and MAP duration.
      Digoxin induced phase 3-EADs and DADs and CsCl or BayK 8644 induced phase 2- and
      phase 3-EADs. Pinacidil shortened MAP duration, suppressed almost all the phase 2
      EADs and some of the phase 3-EADs, but not the DADs. In a few cases, DADs were
      manifested following the abolishment of phase 2-EADs by pinacidil, but this
      phenomenon did not occur in the presence of hexamethonium. Verapamil prolonged
      SCL, did not significantly affect phase 2-EADs, but suppressed almost all of the
      DADs, including those which appeared after pinacidil, and all but one of the
      phase 3-EADs. The effects of pinacidil and verapamil were independent of the mode
      of afterdepolarization induction. A pacing-induced heart rate increase, which
      shortened MAP duration, and vagal stimulation, which prolonged MAP duration,
      attenuated and enhanced phase 2-EADs, respectively. The amplitude of phase 3-EADs
      was inversely related to the heart rate. These data, taken together, are
      consistent with those obtained previously by others in a computer model and
      recent observations on CsCl-induced EADs in the guinea-pig Purkinje fibers in
      vitro which have indicated that the mechanism of phase 2-EADs is different from
      that of DADs and that late phase 3-EADs generated under conditions of Ca2+
      overload and DADs share similar properties.

PMID- 9248850
TI  - Changes in coagulation and fibrinolytic parameters caused by extracorporeal
      circulation.
AB  - During cardiopulmonary bypass (CPB) mechanical stress and the contact of blood
      with artificial surfaces lead to the activation of pro- and anticoagulant systems
      and the complement cascade, and to changes in cellular components. This
      phenomenon causes the "postperfusion-syndrome", with leukocytosis, increased
      capillary permeability, accumulation of interstitial fluid, and organ
      dysfunction. In this study, we focused on the influence of the extracorporeal
      circulation, sternotomy, and heparin administration on the activation of
      coagulation and fibrinolysis. In 15 patients we investigated coagulation
      parameters before, during and post CPB, i.e., fibrinogen, antithrombin (AT) III,
      thrombin-antithrombin complex (TAT), prothrombin fragments F1 + 2 (F1 + 2),
      factor (F) XIIa, tissue factor (TF), and parameters of the fibrinolytic system,
      i.e., plasmin-antiplasmin-complex (PAP), D-dimer, tissue-plasminogen-activator
      (tPA), urokinase-type plasminogen activator (uPA), and plasminogen-activator
      inhibitor type 1 (PAI 1). The results demonstrate distinct alterations in the
      above mentioned parameters. Despite administration of a high dose of heparin
      (activated clotting time [ACT] > 450s) combined with a low dose of aprotinin,
      activation of the coagulation and fibrinolytic pathways was observed. We found
      this activation was mainly caused by CPB and not by sternotomy. The activation of
      coagulation was due to foreign surface contact (F XII => F XIIa) as well as to an
      effect of tissue factor release in the late phase of CPB. The enhanced
      fibrinolytic activity during CPB was, at least in part, caused by tPA and was
      followed by PAI 1 release.

PMID- 9248851
TI  - Increase in the lumen of the femoral artery in dogs with an arteriotomy encircled
      by glutaraldehyde-tanned calf pericardium.
AB  - A fast and simple experimental method of arterioplasty that produces enduring
      enlargement of the lumen of large arteries is described. We studied the long-term
      intraluminal patency of femoral arteries of four dogs subjected to a procedure in
      which a longitudinal 3-cm loophole was made in the artery and left open inside a
      girdling cylinder of glutaraldehyde-tanned calf pericardium. One year later,
      Doppler ultrasound and histological studies were performed in the operated and
      contralateral arteries. Lasting enlargement of the lumen was obtained along the 3
      cm arteriotomy. The mean cross-sectional internal diameter in the middle of the
      surgical area was 2.2 +/- 0.1 mm, in contrast to 1.2 +/- 0.2 mm in the non
      operated contralateral artery (P < 0.01). The ultrasound study showed an increase
      in blood flow and histological analysis demonstrated a threefold increase in the
      internal area of the arterial lumen, and new endothelium, which fully covered the
      operated segment. Our results showed an enduring increase in the lumen in
      segments of large arteries subjected to our new arterioplasty procedure.

PMID- 9248852
TI  - p53 and CD44 as clinical markers of tumour progression in colorectal
      carcinogenesis.
AB  - Recent advances in molecular genetics have importantly improved our understanding
      of the development of colorectal cancer. The present review gives an overview of
      the clinical value of the tumour-suppressor gene, p53, and the CD44 cell adhesion
      molecule in colorectal cancer and the pitfalls encountered in the
      immunohistochemical detection of these proteins. Immunohistochemistry potentially
      forms a procedure applicable for routine diagnosis and prognostication.
      Therefore, p53 expression and the independent prognostic importance of CD44v6
      expression is given particular emphasis, and other molecular events underlying
      colorectal carcinogenesis are only mentioned briefly.

PMID- 9248853
TI  - Localization of eukaryotic initiation factor 2 in neuron primary cultures and
      established cell lines.
AB  - Eukaryotic initiation factor 2 (eIF-2) is a heterotrimeric protein with subunits
      alpha, beta and gamma that forms a ternary complex with Met-tRNA and GTP. It
      promotes the binding of Met-tRNA to ribosomes and controls translational rates
      via phosphorylation/dephosphorylation mechanisms. By means of immunofluorescence
      and post-embedding immunocytochemistry of intact cells and quantitative
      immunoblotting of cell extracts, the cellular distribution of the initiation
      factor has been examined in primary neuronal cultures as well as in two
      established cell lines: PC12 phaeochromocytoma cells and rat pituitary GH4C1
      cells. Our results indicated that the initiation factor is located not only in
      the cytoplasm but also in the nuclei of the cultured neurons and cell lines. In
      the cytoplasm, immunocytochemical studies reveal that the factor is present
      mainly in those areas that are rich in ribosomes. In the nucleus, the
      immunolabelling of eukaryotic initiation factor 2 verified the presence of gold
      particles in both nucleolar and extranucleolar areas. The specific distribution
      of this factor on both sides of the nuclear envelope suggests that it might have
      some nuclear-related function(s) besides its already known role in the control of
      translation.

PMID- 9248854
TI  - South Asians with ulcerative colitis exhibit altered lectin binding compared with
      matched European cases.
AB  - Ulcerative colitis is associated with abnormalities of mucin synthesis and
      secretion, features that may also be associated with malignant change. It has
      been shown that South Asians in Britain have a high incidence of ulcerative
      colitis but a low incidence of colorectal carcinoma compared with their European
      counterparts. Previous studies have demonstrated changes in colonic mucin
      sialylation and sulphation in both South Asian and European cases with ulcerative
      colitis. This was related to disease severity, but changes were also found in
      quiescent disease. The aim of the present study was to determine glycoconjugate
      expression in the colon from South Asian cases and to compare results with those
      from a group of affected Europeans. Glycans were identified in formalin-fixed,
      paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and
      from 11 European patients with a similar degree of colitis, by the application of
      10 biotinylated lectins. These were directed against a range of sialyl, fucosyl
      and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin-peroxidase
      revealing system and semiquantitative assessment. The South Asian group showed a
      reduction in the binding of agglutinins from Sambucus nigra in the apical
      membranous region of enterocytes, and a decrease in apical Maackia amurensis
      agglutinin binding. These results suggest that South Asians with ulcerative
      colitis show a different distribution of terminal N-acetyl neuraminyl residues,
      either in their alpha-2,6 or alpha-2,3 linkage, compared with their European
      counterparts. The changes in sialylation observed in European cases compared with
      normal disease-free control subjects were present in quiescent disease, but were
      also related to disease activity. Their absence in Asians with ulcerative colitis
      may imply an inherent, genetically determined variation in this group, which may
      also play a part in their reduced risk of subsequent malignancy.

PMID- 9248855
TI  - Alterations in gastrin cells induced by short-term omeprazole treatment in the
      rat antrum: an immunocytochemical and in situ hybridization study.
AB  - Gastrin is a hormonal regulator of gastric acid secretion and a trophic stimulant
      of acid-producing gastric mucosa. The blockage of acid secretion has been
      reported to cause hypergastrinaemia and gastrin cell hyperplasia. These findings
      suggest that achlorhydria may stimulate gastrin gene expression in gastrin cells.
      In this study, we aimed to determine the alterations of gastrin mRNA by non
      radioactive in situ hybridization, and also to compare the localization of
      transcripts and protein products of the same gene by immunocytochemistry in an
      acid inhibition environment provided by omeprazole. Female Sprague-Dawley rats,
      weighing 200-250 g, were divided into three groups. The first group was the
      control group (eight rats). The second group (eight rats) was given 20 mg kg-1
      day-1 omeprazole as intragastric instillations for 4 days. The third group (eight
      rats) was given 100 mg kg-1 day-1 omeprazole as in the second group. Serum
      gastrin levels in the two groups treated with omeprazole showed a statistically
      significant increase (P < 0.001) compared with the control group. The omeprazole
      treated groups also showed an increase in the number of immunoreactive gastrin
      cells in the pyloric mucosa and an enhancement in the intensity of
      immunoreaction. Cells containing gastrin mRNA signals were observed in the upper
      regions of the pyloric glands in the pyloric sections of the control group and in
      both experimental groups.

PMID- 9248856
TI  - Identification of leucocyte surface antigens in paraffin-embedded bovine tissues
      using a modified formalin dichromate fixation.
AB  - A modified fixative of formalin dichromate was combined with a cold embedding
      procedure for the preservation of bovine leucocyte surface antigens. Fourteen
      monoclonal antibodies recognizing seven bovine leucocyte surface antigens
      (BoCD1w2, BoCD4, BoCD8, BoWC1, BoWC3, BoWC4 and BoIgM) were applied as primary
      antisera in a sensitive avidin-biotin-peroxidase complex detection method. The
      staining results were compared with those obtained in cryostat and routinely
      formalin-fixed sections of corresponding tissue samples. Using the modified
      formalin dichromate fixative and the cold embedding procedure, all the leucocyte
      surface antigens tested were detectable immunohistologically in paraffin sections
      with a generally more distinct staining than in traditionally processed tissues.
      Morphological structures were better preserved than in cryostat sections but, to
      some extent, were poorer when compared with routinely formalinfixed tissues.
      However, this method suggests that there are only mild masking effects and
      provides an alternative to the use of unfixed material, particularly for
      morphological-immunohistochemical investigations.

PMID- 9248857
TI  - Immunocytochemical localization of transforming growth factor alpha, epidermal
      growth factor and epidermal growth factor receptor in the cat endometrium and
      placenta.
AB  - This study was undertaken to determine the immunocytochemical localization of
      transforming growth factor alpha, epidermal growth factor and epidermal growth
      factor receptor in the endometrium of ovariectomized cats treated with oestradiol
      17 beta and/or progesterone and in the endometrium and placenta of pregnant cats.
      Specific immunostaining was observed for all three antibodies. Moderate
      immunostaining for transforming growth factor alpha was observed in the
      epithelium of ovariectomized and oestrogen-treated cats. Dark epithelial staining
      was observed throughout pregnancy. The epithelial cells in progesterone-treated
      and peri-implantation animals contained dense deposits of reaction product, which
      were not reduced in intensity when immunoabsorbed antiserum was used. For
      epidermal growth factor, light-moderate epithelial staining was observed in
      ovariectomized and steroid-treated animals, and this increased in pregnant cats.
      Stromal staining for both the transforming and the epidermal growth factors was
      limited in steroid-treated animals and increased as pregnancy continued. Dark
      staining for epidermal growth factor receptor was observed in the epithelium and
      stroma in all the animals studied. The tips of surface epithelial convolutions in
      the non-implantation sites were always more darkly stained than in other regions
      of the surface epithelium. Staining in the placental trophoblast was limited to
      the syncytiotrophoblast for the two growth factors and the cytotrophoblast for
      the receptor during most of pregnancy and was absent late in pregnancy. The
      placental maternal giant cells contained specific immunoreactivity for all the
      immunogens from the middle of pregnancy to term. This study demonstrates that the
      two growth factors and the epidermal growth factor receptor are present in the
      endometrium and placenta of cats and suggests that these growth factors may play
      an autocrine/paracrine role during reproduction.

PMID- 9248858
TI  - Immunohistochemical localization of fibroblast growth factor-2 in normal and
      brachymorphic mouse tibial growth plate and articular cartilage.
AB  - Epiphyses of the proximal tibiae of 7-week-old normal and homozygous recessive
      brachymorphic mice (bm/bm) were immunostained using a monoclonal antibody to
      basic fibroblast growth factor to determine its expression in growth plate
      cartilage, osteoblasts on the surfaces of the primary spongiosa and articular
      cartilage. In the normal growth plate the immunoreactive factor was present in
      chondrocytes of the proliferating and upper hypertrophic zones but absent from
      lower hypertrophic chondrocytes. Immunostaining was present only in the
      territorial extracellular matrix immediately adjacent to the chondrocytes of the
      proliferating and upper hypertrophic zones. Osteoblasts of the primary spongiosa
      stained heavily in normal mice. Strong staining was observed in intermediate zone
      articular chondrocytes. Cells in the superficial layer of articular cartilage
      were unstained. The extracellular matrix of the articular cartilage was
      completely free of immunostaining. In contrast, the reduced size of bm/bm growth
      plates was accompanied by significantly reduced staining intensity in
      proliferating and upper hypertrophic chondrocytes, and staining was absent from
      the territorial extracellular matrix of all zones of the bm/bm growth plate.
      Osteoblasts of the primary spongiosa of bm/bm mice stained less than those of
      normal mice. Articular cartilage chondrocytes in the intermediate zone stained
      with less intensity in bm/bm mice, and the cells of the superficial layer were
      unstained. The extracellular matrix of bm/bm articular cartilage was completely
      free of staining. Brachymorphic epiphyseal growth plate and articular
      chondrocytes, and osteoblasts in the primary spongiosa, express reduced amounts
      of immunoreactive fibroblast growth factor-2. This phenotypical characteristic
      may be associated with abnormal endochondral ossification and development of bone
      in brachymorphic mice.

PMID- 9248860
TI  - Effect of thalidomide on apoptosis of lymphocytes and neutrophils.
AB  - Thalidomide causes congenital anomalies and it is immunomodulatory. These
      properties could be explained by an ability to alter the orderly process of
      programmed cell death during embryogenesis and modulation of apoptosis of
      lymphoid and/or myeloid cells in the immune response. Apoptosis of lymphoid and
      myeloid cells was studied by measuring the percentage of cells capable of
      excluding propidium iodide and expressing phosphatidylserine on their outer
      membrane. In addition, expression of Fc gamma RIII (CD16) was used to assess
      neutrophil apoptosis. Thalidomide did not affect the rate of apoptosis of CTLL-2
      cells deprived of, or supplemented with, IL-2; of T-cells (mitogen-stimulated or
      resting) or of neutrophils. However, neutrophils obtained from HIV-infected
      patients treated with thalidomide showed reduced expression of CD16, a surrogate
      marker for apoptosis of neutrophils. Thalidomide's effect on neutrophil apoptosis
      in vivo warrants further investigation.

PMID- 9248859
TI  - Enhancement of natural killer cell activity and T and B cell function by buffered
      vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C.
AB  - After exposure to many toxic chemicals, NK function can be decreased
      significantly. Weeks or months later, natural killer (NK) function can rebound to
      normal levels in some and can be suppressed for prolonged periods of time in
      other patients. In view of this, we decided to study the effect of buffered
      vitamin C on NK, T and B cell function in patients who had been exposed to toxic
      chemicals. After the first blood draw, 55 patients immediately ingested
      granulated buffered vitamin C in water at a dosage of 60 mg/Kg body weight.
      Exactly 24 hours later, blood was again drawn for a follow-up study of NK, T and
      B cell function. Vitamin C in high oral dose was capable of enhancing NK activity
      up to ten-fold in 78% of patients. Lymphocyte blastogenic responses to T and B
      cell mitogens were restored to the normal level after vitamin C usage. Signal
      transduction enzyme protein kinase C (PKC) appeared to be involved in the
      mechanism of induction of NK activity by vitamin C. We conclude that immune
      functional abnormalities can be restored after toxic chemical exposure by oral
      usage of vitamin C.

PMID- 9248862
TI  - Simultaneous effects of lead and cadmium on NK cell activity and some phenotypic
      parameters.
AB  - Lead and cadmium are common environmental contaminants that alter the immune
      response. Natural killer cell (NK) cytotoxicity and phenotypic parameters are
      crucial immune responses, but little is known about the effects of these metals
      on these responses. In the present paper, we investigated the simultaneous
      effects of lead and cadmium on NK cell activity and CD4+, CD20+ cell percentages
      in the workers and compared the data with control and lead-exposed groups. We
      conclude that simultaneous exposure to lead and cadmium is not associated with an
      impairment of either NK cell function of CD4+ cell percentage. On the other hand,
      CD20+ cell percentage was found higher in lead+cadmium exposed group than
      controls.

PMID- 9248861
TI  - In vitro effects of melatonin on mitogen-induced lymphocyte proliferation and
      cytokine expression in young and old rats.
AB  - Melatonin (MLT) treatment in vivo has been shown to have immunomodulatory and
      anti-immunosenescent effects in the mouse model. In the present report, the in
      vitro effect of MLT on mitogen-induced lymphocyte proliferation and cytokine
      expression was evaluated in a rat model. Splenic lymphocytes were isolated from
      young (6 months) and old (24 months) F344 rats and were incubated with MLT in the
      presence or absence of mitogens. The proliferative response to concanavalin A
      (ConA) or PMA plus ionomycin was measured in splenocytes or T cells isolated from
      young and old rats. In addition, the induction of interleukin-2 (IL-2) and
      interferon-gamma (IFN-gamma) production was measured in MLT-treated and untreated
      lymphocytes isolated from young and old rats. The ConA-induced lymphocyte
      proliferation and IL-2 expression were significantly lower and induction of IFN
      gamma production was significantly higher in splenocytes and purified T cells
      isolated from old rats compared to splenocytes and T cells isolated from young
      rats. Treatment of lymphocytes with MLT did not significantly alter ConA-induced
      lymphocyte proliferation or IL-2 or IFN-gamma expression in lymphocytes isolated
      from either young or old rats. On the basis of these data, we conclude that in
      vitro MLT treatment had no immunomodulatory effect on lymphocytes from rats.

PMID- 9248863
TI  - Influence of Photofrin on the hematopoietic accessory function of murine
      peritoneal cells.
AB  - The porphyrin photochemotherapeutic agent Photofrin stimulates hematopoietic
      activity within the bone marrow (BM) and spleens of normal mice. We found that
      the intraperitoneal (i.p.) administration of Photofrin also caused a 3-4 fold
      increase in peritoneal cell (PC) numbers, particularly cells bearing granulocyte
      surface antigens. Little granulocyte-macrophage progenitor activity was
      detectable within the PC population of control and Photofrin-injected mice
      suggesting that Photofrin had elicited an influx of inflammatory cells into the
      region. In contrast to cells from control animals, PC obtained 6 h to 168 h after
      the i.p. injection of Photofrin exhibited a consistently inferior capacity to
      support the growth of BM colony forming units granulocyte-macrophage (CFU-GM).
      When PC from control or Photofrin-treated mice were added to the BM culture
      system in the presence of defined growth factors there was no effect on the
      number of colonies formed. This finding indicated that negative regulatory
      elements were not responsible for the reduced hematopoietic accessory activity
      exhibited by PC from Photofrin-treated mice. Supernatants conditioned by PC from
      Photofrin-injected mice poorly supported BM CFU-GM growth in vitro and in
      contrast to PC supernatants prepared from control mice did not contain detectable
      amounts of granulocyte-macrophage colony stimulating factor (GM-CSF). The
      cellular changes which occur within the peritoneal cavity represent bystander
      events not directly related to the hematostimulatory action of Photofrin.

PMID- 9248865
TI  - Immunoglobulin E and autoantibodies in mercury-exposed workers.
AB  - In this work we have studied the serum immunoglobulin E (IgE) levels and the
      concentration of anti-DNA and anti-nucleus antibodies in mercury-exposed workers.
      The study group consisted of 36 workers from a mercury producing plant, with a
      mean age of 27 years and a mean exposure period to mercury of 19 months. At the
      time of testing, and for the three previous months, the exposed population had
      urinary mercury levels below the currently accept limit of 50 ug/g creatinine.
      Significantly increased IgE levels was found in the mercury-exposed individuals.
      Moreover, a moderate negative correlation (r = -0.43 P < 0.05) between the length
      of exposure to mercury and IgE levels was observed. Anti-DNA and anti-nucleus
      antibodies were not detected in these workers. These results suggest that the
      humoral immune response is an indicator of cellular changes in workers
      chronically exposed to mercury, even in those with urinary mercury concentrations
      within levels considered safe in the occupational area.

PMID- 9248866
TI  - Sulfide influence on polymorphonuclear functions: a possible role for Ca2+
      involvement.
AB  - Polymorphonuclear cells (PMN) of gingival sulcus play an important role in host
      defense against periodontal tissue-invading bacteria, but their phagocytic
      activity is conditioned by several virulence factors released by oral pathogens.
      In this report we have studied the influence of sulfide, a toxic bacterial
      metabolite, on the main PMN functions: chemotaxis, degranulation and oxidative
      burst. PMN exposed to sodium sulfide (up to 2 mM) used as a source of H2S showed
      a depression of the calcium-dependent cytoskeleton activities such as chemotaxis
      and azurophilic granule release induced by FMLP. No effect was observed on the
      calcium-independent specific granule release obtained by PMA. These data were in
      agreement with the sulfide inhibition of cytosolic free Ca2+ concentration
      [Ca2+]i increase normally induced by ionomycin. On the other hand, hydrogen
      sulfide was able to prime PMN for a stronger oxidative response both to calcium
      dependent or calcium-independent stimulation. This finding may account for a more
      efficient oxidative killing under reoxygenation of the anaerobic infectious
      areas.

PMID- 9248864
TI  - Carbamazepine affects neutrophil function through an action on peripheral
      benzodiazepine receptors.
AB  - The aims of this study were to assess the possible role of peripheral
      benzodiazepine receptors (pBZrs)1 in mediating the in vitro effects of
      carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to
      investigate neutrophil function and pBZr expression in patients with epilepsia on
      CBZ monotherapy for at least 1 year. In vitro CBZ (42-168 microM) concentration
      dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl
      phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did
      not affect random migration, phagocytosis index, phagocytosis frequency, NBT
      reduction frequency, C. albicans lethality index and resting superoxide
      production. The pBZr antagonist PK 11195 (1 microM, per se ineffective) reversed
      the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum
      or FMLP. The pBZr agonist Ro 5-4864 (10-100 microM) mimicked the effect of CBZ on
      chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the
      other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy
      had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs
      on neutrophils. These data strongly suggest an involvement of pBZrs in mediating
      the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same
      neutrophil function parameters and overexpression of pBZrs in patients are
      consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.

PMID- 9248867
TI  - A double-blind comparative study of clozapine versus chlorpromazine on Chinese
      patients with treatment-refractory schizophrenia.
AB  - Clozapine has been shown to have superior effectiveness compared with classic
      neuroleptics in treating refractory schizophrenia in Caucasians, but its efficacy
      and safety in Chinese have not been adequately studied. Forty Chinese
      schizophrenic patients were recruited in a 12-week, double-blind, comparative
      trial. Twenty-one patients were randomly assigned to clozapine treatment and 19
      to chlorpromazine treatment. The average dose was 543 +/- 157 and 1163 +/- 228
      mg/day for clozapine and chlorpromazine, respectively. The results showed that
      six clozapine-treated patients (28.6%) had more than 20% improvement in Brief
      Psychiatric Rating Scale score and were classified as responders, whereas none of
      the chlorpromazine-treated patients was classified as a responder. The degree of
      improvement in positive symptoms, negative symptoms and Brief Psychiatric Rating
      Scale scores in the clozapine group was inversely correlated with the severity of
      negative symptoms at entry into the trial. Two clozapine-treated patients were
      withdrawn from the study, one because of leukopenia and nausea, and the other
      because of vomiting and hypotension. Chlorpromazine treatment was prematurely
      discontinued in two patients, because of jaundice and over sedation in one, and
      because of severe weight loss in the other (9 kg). The rate of moderate-to-severe
      sialorrhea was high in clozapine-treated patients (28.6%). Two clozapine-treated
      patients and two chlorpromazine-treated patients showed significant improvement
      in previously existing tardive dyskinesia and one chlorpromazine-treated patient
      exhibited aggravation of tardive dyskinesia. The results of this study indicate
      that clozapine treatment might have advantages over chlorpromazine for Chinese
      schizophrenic patients who are refractory to typical neuroleptic treatment.

PMID- 9248868
TI  - A double-blind study of fluvoxamine and clomipramine in the treatment of
      obsessive-compulsive disorder.
AB  - A double-blind trial was carried out to assess the efficacy and safety of
      fluvoxamine, a selective serotonin reuptake inhibitor, in comparison with
      clomipramine, a classical tricyclic antidepressant, in the treatment of obsessive
      compulsive disorder. A total of 26 individuals with obsessive-compulsive disorder
      and with no comorbid disorders at baseline were included in the study. The
      obsessive-compulsive disorder symptom severity was rated using the Yale-Brown
      Obsessive-Compulsive Scale and the Clinical Global Impression Scale. The primary
      efficacy measures indicated an equal improvement in the two groups (38% in the
      patients taking fluvoxamine and 40% in those taking clomipramine, as compared
      with baseline values), but onset was faster in the clomipramine group. Side
      effects, in particular anticholinergic side effects, were more prominent in the
      clomipramine group. The present double-blind trial confirms an equal efficacy of
      clomipramine and fluvoxamine in obsessive-compulsive patients. Although
      clomipramine had a faster onset, fluvoxamine was better tolerated, so that it
      seems more suitable for long-term treatment of obsessive-compulsive patients.

PMID- 9248869
TI  - An open-label study of duloxetine hydrochloride, a mixed serotonin and
      noradrenaline reuptake inhibitor, in patients with DSM-III-R major depressive
      disorder. Lilly Duloxetine Depression Study Group.
AB  - Duloxetine hydrochloride, a mixed reuptake inhibitor of serotonin and
      noradrenaline, was studied in a 6 week open-label uncontrolled multicentre design
      at a dose of 20 mg daily both in in- and outpatients meeting DSM-III-R criteria
      for unipolar major depressive disorder. Seventy-nine patients took part in the
      study. The mean score on the 17-item Hamilton Depression Rating Scale at baseline
      was 24.9 (SD 4.4), decreasing to 8.5 (SD 7.8) after 6 weeks using a last
      observation carried forward analysis. Clinical response, defined as a 50%
      reduction in 17-item Hamilton Depression Rating Scale scores, occurred in 78.2%
      of patients, whereas remission, defined as a 17-item Hamilton Depression Rating
      Scale score of < or = 6, occurred in 60.3% of patients. Duloxetine hydrochloride
      was safe and well tolerated in this patient population.

PMID- 9248870
TI  - Lack of effect of amitriptyline on risperidone pharmacokinetics in schizophrenic
      patients.
AB  - The interaction between plasma concentrations of the tricyclic antidepressant
      amitriptyline and the metabolism of the new antipsychotic risperidone was studied
      in 12 patients with chronic schizophrenia. Each patient received 3 mg risperidone
      twice a day for 28 days. Amitriptyline was coadministered at doses of 50 mg/day
      on day 15 and 100 mg/day on days 16 to 21. Amitriptyline did not significantly
      affect the mean plasma concentrations or pharmacokinetics of risperidone in
      schizophrenic patients or influence the antipsychotic fraction (the total
      concentration of risperidone and 9-hydroxyrisperidone, its primary and
      biologically active metabolite). These results suggest that risperidone dose need
      not be adjusted when coadministered with amitriptyline at doses up to 100 mg/day
      in schizophrenic patients.

PMID- 9248871
TI  - Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the
      delirious state? A comparison of the effects of mianserin and haloperidol on
      delirium.
AB  - Sixty-six patients (47 men, 19 women, mean age 65 years) with delirium were
      treated with mianserin (10-60 mg/day) or haloperidol (2-6 mg/day) at Kurume
      University Hospital. The clinical effects of these drugs were compared before and
      after treatment using the Delirium Rating Scale. At the same time, blood was
      sampled to analyse plasma mianserin, free-3-methoxy-4
      hydroxyphenyl(ethylene)glycol (MHPG) and homovanillic acid concentrations. Marked
      improvement after 1 week was observed in 69.4% of patients undergoing mianserin
      treatment, and in 70.6% of those receiving haloperidol. A statistically
      significant difference in the clinical effects of these drugs was not observed.
      Although improvement in the delirious state and a decrease in the plasma free
      MHPG concentration were observed after drug administration, the plasma free
      homovanillic acid concentration showed no significant change. The higher plasma
      free-MHPG concentration in the delirious state suggests the existence of a
      preparatory state whereby noradrenaline metabolism is involved in the appearance
      of the abnormal behaviour associated with delirium. These data suggest that free
      MHPG concentrations could potentially be used as a predictor of delirium.

PMID- 9248872
TI  - Relationship between single oral dose pharmacokinetics of alprazolam and
      triazolam.
AB  - The relationship between the single oral dose pharmacokinetics of alprazolam and
      triazolam was studied in 10 healthy male volunteers. Each subject took single
      oral doses of alprazolam 0.8 mg and triazolam 0.5 mg with at least a 2 week
      interval between each dose. Blood samplings were performed up to 48 h after
      alprazolam dosing and up to 12 h after triazolam dosing. Plasma concentrations of
      both drugs were measured by high-performance liquid chromatography. The means +/-
      standard deviation of the peak plasma concentration, the total area under the
      plasma concentration-time curve and the elimination half-life of alprazolam were
      11.3 +/- 3.1 ng/ml, 232.4 +/- 59.2 ng/h/ml and 16.5 +/- 4.6 h, respectively, and
      those of triazolam were 3.2 +/- 1.0 ng/ml, 11.8 +/- 5.2 ng/h/ml and 2.5 +/- 1.1
      h, respectively. There was no significant correlation between the two drugs in
      any pharmacokinetic parameters (r = 0.35, 0.25 and 0.50). The present study thus
      suggests that the single oral dose pharmacokinetics of alprazolam and triazolam
      do not correlate well in individuals.

PMID- 9248874
TI  - Lack of effect of vitamin E on serum creatine phosphokinase in patients with long
      term tardive dyskinesia.
AB  - Changes in serum creatine phosphokinase have been associated with exacerbation of
      tardive dyskinesia. Vitamin E, a drug suggested to be effective in the treatment
      of tardive dyskinesia, has been implicated as a possible cause of increased
      creatine phosphokinase levels. Ten patients with long-term tardive dyskinesia
      were treated with vitamin E in a double-blind, placebo-controlled crossover
      study. Vitamin E blood levels and creatine phosphokinase serum levels were
      monitored at various phases during the study. There were no significant
      differences between vitamin E and placebo treated patients in their abilities to
      affect tardive dyskinesia or to influence creatine phosphokinase levels. These
      data do not support the hypothesis that administration of vitamin E may alter
      creatine phosphokinase levels in patients with long-term tardive dyskinesia.

PMID- 9248873
TI  - Considering the P450 cytochrome system as determining combined effects of
      antidepressants and benzodiazepines on actual driving performance of depressed
      outpatients.
AB  - Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n =
      22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses
      were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for
      greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking
      them as comedication. Therapeutic and side effects were assessed using
      conventional rating scales. Actual driving performance was assessed during the
      week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test
      that measures standard deviation of lateral position (SDLP). Similar remissions
      in depressive symptoms and side effects occurred in both groups. Patients drove
      with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do
      so but a few drove with progressively rising SDLPs and the overall trends were
      significant in both groups (p < 0.03). A post-hoc multiple regression analysis
      was applied for identifying factors that correlated with SDLP in separate tests
      after the beginning of therapy. At 3 and 6 weeks there were significant (p <
      0.03) relationships involving the same factor; patients who drove with
      progressively higher SDLPs appeared to be those using benzodiazepines that are
      metabolized by a P450 isozyme subject to inhibition by their particular
      antidepressant.

PMID- 9248875
TI  - Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric
      emergency room setting.
AB  - The efficacy of a benzodiazepine was compared with that of a neuroleptic for the
      rapid tranquilization of patients presenting at a psychiatric emergency room
      service. Thirty-seven highly agitated patients exhibiting psychotic symptoms were
      randomly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed
      every 30 min for 4 h. Administration route was either intramuscular injection or
      oral concentrate. Symptom ratings were conducted each hour using double-blind
      procedures. Both medications reduced symptom ratings on the Brief Psychiatric
      Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale.
      Global Clinical Impression scores for the two medication groups did not differ
      significantly either at baseline or at 4 h after entry into the study. However,
      Global Clinical Impression scores of patients in the lorazepam group were less
      severe at intermittent ratings. The groups did not differ on the Brief
      Psychiatric Rating Scale at any rating time. No differences were found either in
      the number of doses administered or in the administration route selected. Given
      the potential for severe extrapyramidal symptoms developing hours or days after a
      single dose of haloperidol, lorazepam may provide an excellent alternative for
      the rapid tranquilization of the acutely agitated psychotic patient in the
      emergency room setting.

PMID- 9248876
TI  - Serotonin syndrome attributed to tramadol addition to paroxetine therapy.

PMID- 9248877
TI  - Factors affecting quality of life of the Korean aged stroke patients.
AB  - Among the most prevalent disabling diseases of old age, stroke is the leading
      chronic condition in Korea. The physical and psychosocial complications of a
      stroke can result in serious limitations on all aspects of one's life that affect
      overall quality of life. This study examines the relative importance of and
      interactions among factors which affect the quality of life of 119 stroke
      patients aged sixty-five and older in Korea. The model uses family support,
      personality (specifically hardiness), economic status, and physical functioning
      as independent variables, and quality of life as a dependent variable. The
      results of this study suggest that physical functioning and physical care by the
      family are important factors influencing quality of life of the aged stroke
      patients. Hardy personality is negatively associated with financial support and
      physical care by the family. These findings have several implications for policy
      development, clinical practice, and future research in this area.

PMID- 9248878
TI  - Aging and the aged in Aesopic fables.
AB  - Little attempt has been made to re-assess the attitudes to aging and old age of
      the ancient-medieval Greek-speaking world on the basis of the literary remains
      (which are common to both) since Richardson (1933). There are however some
      collections (proverbs, sayings, "purple passages" from literature and so forth)
      which include material revealing attitudes which are in fact quite different from
      those of today and which can even be surprising. One such collection, the large
      number of fables which more or less conform to the genre associated with Aesop,
      is here analyzed to isolate the texts which have to do with aging and the
      attitudes they reveal. Of the surprisingly few fables which touch upon the
      matter, most are distinctly complimentary. In most instances the elderly are seen
      to increase, rather diminish, in certain powers other than physical strength.
      Fables are found which characterize them as being astute, intelligent, crafty,
      loyal and, above all, capable of giving sound advice and good leadership when the
      situation requires it of them. The celebrated Fable of the Tortoise and the Hare,
      although it was not specifically interpreted in this way in ancient times, best
      sums up the general attitude: that dogged persistence (the characteristic of the
      elderly) will ultimately prove superior to all the erratic bursts of youthful
      speed anytime. Hence Cicero: "Old age is more spirited than youth, and stronger!"

PMID- 9248879
TI  - Respect redefined: focus group insights from Singapore.
AB  - This article re-examines the meaning of the concept of respect within the context
      of a fast modernizing Asian multicultural society-Singapore. Two key findings
      emerge. First, the meaning of respect both from the perspective of the aged and
      the middle-aged generation has shifted from obedience to courteous behavior.
      Second, in the majority of focus groups members concurred that the degree of
      respect accorded to elders has in general decreased. The focus group methodology
      was used in this research. Bearing in mind the limited sample size (88
      participants) these findings alert us to the need for social scientists to
      monitor perceptual shifts in meaning of concepts critical in the sphere of
      interpersonal relationships. The findings throw light on the subjective views of
      intergenerational relations within the family as well as the community. As such,
      they would be valuable to counselors, social workers, and family therapists.

PMID- 9248880
TI  - Cross-cultural differences in adolescents' perceptions of their grandparents.
AB  - Partial results from a larger Finnish-Polish study on the relations between
      grandchildren, parents, and grandparents are presented here. The results are
      based on a content analysis of essays written by 731 Finnish and Polish
      adolescents between eleven and twenty-one. Older children used more abstract
      descriptions, girls mentioned more personality features and feelings than boys,
      and grandmothers, especially maternal grandmothers were described in the most
      positive terms. The central new finding was that there are highly significant
      cross-cultural differences in the descriptions of grandparents; the Poles
      describe them in more abstract terms even after controlling for age and gender.
      Polish adolescents make more mention of their feelings, their personality, and
      their skills as well as of emotional/intellectual input from them; they use more
      positive terms than do the Finns, but make less mention of activities and
      appearance. These differences between the two cultures are mediated by contact
      frequency, which through its working on the proximal level enables co
      construction of the relationship and the transmission of interactional styles.

PMID- 9248881
TI  - Capsaicin--an effective topical treatment in pain.

PMID- 9248882
TI  - Bacillary angiomatosis, cat-scratch disease, and bartonellosis: what's the
      connection?

PMID- 9248883
TI  - Dermatoepidemiology. II: Causal inference established by a rule called
      "ASSOCIATED".

PMID- 9248884
TI  - A comparison of current acne grading systems and proposal of a novel system.

PMID- 9248886
TI  - Primary localized cutaneous amyloidosis: a clinicopathologic study from Saudi
      Arabia.
AB  - BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) refers to deposition
      of amyloid in apparently previously normal skin with no evidence of deposits in
      internal organs. Certain ethnic groups are particularly predisposed. The
      objective of this study was to investigate the occurrence of PLCA in a hospital
      based set-up and to review the clinico-pathologic findings of histologically
      confirmed cases. METHODS: Methods included a retrospective evaluation of the
      records and paraffin sections of skin biopsies of all patients, diagnosed
      clinically as cutaneous amyloidosis in a tertiary care teaching hospital during
      the period 1987-95. RESULTS: Twenty-one out of 42 suspected cases were
      histologically confirmed as PLCA; the total number of biopsied patients during
      the whole period was 920. Eleven were cases of lichen amyloidosis (LA) and 10
      were of macular amyloidosis (MA). All were adults, and women dominated in MA. The
      mean duration of symptoms was shorter for the latter subtype. Histologically
      epidermal changes were the main differentiating feature between LA and MA.
      CONCLUSIONS: PLCA is a rare chronic progressive skin disorder affecting adults,
      with a prevalence of 0.15 among patients attending the dermatology clinic in a
      tertiary care teaching hospital in Saudi Arabia. There were few differences in
      demographic profile or histochemical characteristics between LA and MA.
      Meticulous histologic examination of sections and even sequential biopsies may be
      needed to confirm the diagnosis in clinically suspected cases.

PMID- 9248885
TI  - Angiocentric T-cell lymphoma presenting as lethal midline granuloma.
AB  - BACKGROUND: Lethal midline granuloma (LMG) is a rare condition characterized by
      rapidly progressive midfacial destruction. Most LMG cases are angiocentric T-cell
      lymphomas and an association with Epstein-Barr virus (EBV) has been reported.
      Cutaneous involvement is poorly described and the prognosis not well documented.
      METHODS: We report a case of angiocentric T-cell lymphoma of the palate that
      presented as LMG with concurrent discrete skin lesions composed of two distinct
      morphologic appearances: indurated nodules and annular plaques. The English
      language literature for LMG-type angiocentric T-cell lymphoma is reviewed and a
      survival analysis of 58 cases with follow-up data (including our own case) is
      performed. RESULTS: The 1- and 5-year survival rates were 45% +/- 7% and 22% +/-
      9%, respectively. Poor survival was associated with advanced age and stage. EBV
      DNA was detected in 16 out of 21 reported cases in which it was sought (including
      our case). CONCLUSIONS: We present photographic documentation of a broader
      spectrum of cutaneous lesions in the LMG-type angiocentric T-cell lymphoma than
      has previously been described, and have confirmed the association with EBV. The
      prognosis is poor. Aggressive therapy such as bone marrow transplantation should
      be considered early in the course.

PMID- 9248887
TI  - Nevus lipomatosus superficialis on the face.

PMID- 9248889
TI  - Solitary plexiform neurofibroma is not pathognomonic of von Recklinghausen's
      neurofibromatosis: a report of a case.

PMID- 9248888
TI  - Kimura's disease.

PMID- 9248890
TI  - Divergent clinical course of epidermodysplasia verruciformis in siblings.

PMID- 9248891
TI  - Granuloma annulare associated with Hodgkin's disease.

PMID- 9248893
TI  - Subcutaneous fat necrosis of the newborn.

PMID- 9248892
TI  - Polymorphic eruption of pregnancy.

PMID- 9248894
TI  - The changing referral pattern in Danish dermatology--Rigshospitalet, Copenhagen,
      1986-1995.

PMID- 9248895
TI  - Cost-benefit of oral acyclovir in the treatment of herpes zoster.
AB  - BACKGROUND: Oral acyclovir is a costly antiviral agent shown to be effective in
      the treatment of herpes zoster. Herpes zoster runs a relatively benign course in
      young, healthy individuals, as compared with elderly and immunologically
      compromised patients, in whom complications are common. This study attempts to
      assess the cost-benefit of treatment with oral acyclovir in young healthy adults
      with herpes zoster. PATIENTS AND METHODS: The records of 42 healthy young adults
      suffering from herpes zoster and treated with oral acyclovir (800 mg five times
      daily for 7 days) were compared with those of 40 healthy young adults with herpes
      zoster seen during the same period but treated without oral acyclovir. The
      duration of zoster-associated pain and the presence of complications were noted.
      RESULTS: There was no statistically significant difference in the duration of
      zoster-associated pain between the two groups of patients (P = 0.11). Other
      complications of herpes zoster were few and similar in the two groups.
      CONCLUSIONS: At a cost of $250 to $300 for a 7-day course of oral acyclovir, the
      use of this antiviral agent in healthy young individuals with herpes zoster is
      not justified, especially in developing countries with limited resources.

PMID- 9248898
TI  - Toxic shock syndrome in AIDS.

PMID- 9248896
TI  - A 2-year study of liquid nitrogen therapy in cutaneous leishmaniasis.
AB  - BACKGROUND: Among the different modalities for treatment of cutaneous
      leishmaniasis, liquid nitrogen is considered an effective therapy with very mild
      side-effects. METHODS: A study was conducted using liquid nitrogen topically for
      the treatment of cutaneous leishmaniasis in the King Hussain Medical Centre,
      Amman-Jordan. Among 468 patients of cutaneous leishmaniasis, 293 were treated
      with liquid nitrogen and the rest were treated with other known treatment
      modalities. RESULTS: Of the patients treated with cryo surgery liquid nitrogen,
      215 of 293 permitted appropriate follow-up; the clinical response was significant
      and effective. No systemic adverse effects were noted. Mild cutaneous
      complications were infrequent, and included hypopigmentation, hyperpigmentation,
      and scar formation. CONCLUSIONS: From the results of this study, liquid nitrogen
      therapy may be considered an effective treatment for cutaneous leishmaniasis.

PMID- 9248897
TI  - Intralesional therapy of American cutaneous leishmaniasis with pentavalent
      antimony in Rio de Janeiro, Brazil--an area of Leishmania (V.) braziliensis
      transmission.
AB  - BACKGROUND: The drug of choice for leishmaniasis is pentavalent antimony and
      different regimens are under continuous evaluation. The ideal therapy should be
      simple, effective, and with no or minor side-effects. In this paper we have
      studied the efficacy of intralesionally applied antimony in New World cutaneous
      leishmaniasis. METHODS: Seventy-four patients from Rio de Janeiro state, Brazil,
      and presenting with single ulcerative cutaneous lesions mainly located on the
      trunk or extremities were enrolled in the study. The drug employed was N-methyl
      glucamine (425 mg of Sbv in each 5 ml ampoule). Each lesion was infiltrated with
      the drug at the four cardinal points in order to achieve complete blanching.
      RESULTS: Of the 74 patients, 59 (80%) were healed after a 12-week interval.
      Extensive follow-up (up to 10 years) disclosed no relapses or the development of
      mucosal lesions. CONCLUSIONS: The aim of therapy in New World cutaneous
      leishmaniasis is the healing of the cutaneous lesion and the prevention of late
      mucosal damage. Both conditions were achieved with the treatment employed with no
      side-effects and a considerable decrease in costs. In addition, the method is
      easy to apply in the field.

PMID- 9248899
TI  - Basement membrane folds on plantar skin.

PMID- 9248900
TI  - Silicone cream occlusive dressing in postoperative care of chemical peels.

PMID- 9248901
TI  - Transient acantholytic dermatosis (Grover's disease) in a patient with
      progressive systemic sclerosis treated with D-penicillamine.

PMID- 9248902
TI  - Sertraline: lack of therapeutic efficacy in patients with delusions of
      parasitosis and dermatitis artefacta.

PMID- 9248903
TI  - Violence: the relation between seriousness of injury and outcome in the criminal
      justice system.
AB  - OBJECTIVE: To investigate the relation between injury severity in assault,
      offence seriousness, and outcome in the criminal justice system. METHODS:
      Prospective random sample of 93 assault victims who attended hospital were
      interviewed and examined and followed through the criminal justice system.
      Patient and police interviews were carried out at Bristol Royal Infirmary
      accident and emergency and outpatient departments, wards, and in Avon police
      stations and criminal courts. Severity of injury (injury severity score [ISS]
      assessed by the major trauma outcome study group), offence seriousness (Delphi
      panel of criminologists), and outcome in the criminal justice system were
      recorded. RESULTS: Median ISS was 4 (range 1-17). There was no significant
      correlation between ISS and outcome in the CJS (rs = 0.07). There was a weak
      correlation between offence seriousness and outcome (rs = -0.24, P = 0.019).
      CONCLUSIONS: Outcome in the criminal justice system was not predictable from
      injury severity scores and was only weakly linked to offence seriousness.
      Contacts with medical services are opportunities for protecting those at risk of
      violence.

PMID- 9248904
TI  - Intravenous chlorpromazine versus intramuscular sumatriptan for acute migraine.
AB  - OBJECTIVE: To establish whether there is any difference in the efficacy of a
      chlorpromazine regimen and a sumatriptan regimen for the management of the pain
      of acute severe migraine. SETTING: Two urban teaching hospital emergency
      departments. METHODS: Prospective, randomised, unblinded, crossover trial. All
      patients received intravenous metoclopramide 10 mg and 1000 ml of normal saline
      over 1 h; 20 were then randomised to receive intramuscular sumatriptan 6 mg and
      23 to receive intravenous chlorpromazine, 12.5 mg increments to a maximum of 37.5
      mg. Response to treatment was measured using visual analogue pain scales.
      RESULTS: No difference in efficacy between the sumatriptan regimen and the
      chlorpromazine regimen was found. Adverse effects were mild and equally
      distributed between the groups. CONCLUSIONS: The chlorpromazine and sumatriptan
      regimens studied are both very effective for the relief of the headache of severe
      migraine.

PMID- 9248905
TI  - Characteristics of self referred patients attending minor injury units.
AB  - OBJECTIVE: To examine the characteristics, expectations, and use of health
      services of patients who self refer to minor injury units (MIUs). DESIGN:
      Preconsultation questionnaire administered to self referred patients attending
      with new problems. SETTING: Two MIUs in south Kent. MAIN RESULTS: Of 312 self
      referred patients, 265 (84.9%) presented with minor injuries and 47 (15.1%) with
      illnesses. In most cases the illness/injury was of recent origin: 119 (38.1%)
      said it was of less than six hours' duration and 115 (27.6%) between 6 and 24
      hours' duration. Most (214; 68.6%) came from home, and for 268 (85.9%) it took 10
      min or less to get to the MIU. 79 patients (25.3%) had used the MIU on on e to
      two occasions in the previous year, and 21 (6.7%) had used it on three or more
      occasions. In the same period, 44 (14.1%) had attended on accident and emergency
      (A&E) department on one to two occasions, and 17 (5.4%) has used A&E on three or
      more occasions, while 108 (34.6%) had been to a general practitioner on one to
      two occasions, and 144 (46.1%) on three or more occasions. If there had been no
      MIU available, 151 patients (48.4%) said they would have attended an A&E
      department, and 91 (29.4%) said they would have attended their general
      practitioner. The remainder would have self treated or were unsure. CONCLUSIONS:
      While the availability of an intermediate tier of care appears to result in
      greater overall workload for the health service, this must be balanced against
      the clinical and social costs involved in different patterns of service
      provision. The cost-effectiveness of these services need further study.

PMID- 9248906
TI  - Medical involvement in prehospital care--a transatlantic comparison.
AB  - The role of doctors in prehospital care in the United Kingdom and the USA was
      compared using information obtained from a visit to the city of Houston emergency
      medical service (Houston, Texas) and from a review of published reports. The
      involvement of full time specialist emergency medical services physicians has
      been crucial to the development of improved standards of practice within American
      prehospital care. The specialty of accident and emergency medicine should support
      provision of medical advice to the ambulance services by closer liaison with
      ambulance service trusts and the formalisation of training in prehospital care to
      specialist registrars.

PMID- 9248907
TI  - Prehospital emergency rapid sequence induction of anaesthesia.
AB  - OBJECTIVE: To determine the number of and reasons for rapid sequence inductions
      done by accident and emergency (A&E) doctors out of hospital as part of the
      activities of the MEDIC 1 Flying Squad. "Rapid sequence induction" was defined as
      any attempted endotracheal intubation accompanied by use of drugs to assist
      intubation and ventilation, including opiates, benzodiazepines, intravenous and
      topical anaesthetics, and neuromuscular blocking drugs. METHODS: Retrospective
      study of all MEDIC 1 and A&E records over the period 1 February 1993 to 28
      February 1996 (37 months). The anaesthetic technique used, drugs used,
      complications, difficulties, reasons for induction out of hospital, and grade of
      doctor performing the technique were determined. RESULTS: Various anaesthetic
      techniques were used to secure the airway definitively by endotracheal
      intubation. Several difficulties were encountered in the prehospital setting, all
      of which were dealt with successfully. CONCLUSIONS: The lack of complications
      related to rapid sequence induction in prehospital care suggests that this
      technique is safe when done by A&E doctors on appropriate patients.

PMID- 9248908
TI  - Capnography for monitoring non-intubated spontaneously breathing patients in an
      emergency room setting.
AB  - OBJECTIVE: To examine the feasibility of using expiratory capnography as an
      indicator of airway obstruction in non-intubated resuscitation room patients.
      METHODS: Patients with potential respiratory compromise admitted to the
      resuscitation room were assessed for widespread expiratory wheeze. This was taken
      as clinical evidence of airways obstruction. Expiratory capnograms of these
      patients and patients who had no wheeze were obtained. The traces were analysed
      for basic morphology and where appropriate the slope ratio (SR) between phase 1
      (S1) and phase 2 (S2) of the trace was obtained. RESULTS: Thirty eight patients
      with a variety of clinical conditions causing potential or actual respiratory
      impairment were studied. All patients tolerated the nasal capnogram cannulae.
      Twelve had no clinical evidence of airway obstruction and all had capnograms with
      normal morphology. Eleven of these were analysed further. The mean value for SR
      was 7.57 (SEM 0.18), 95% confidence interval 6.37 to 8.77. Twenty six patients
      had clinical evidence of airway obstruction "sharks fin" morphology. Fourteen of
      these were analysed to determine SR. The mean value was 31.9 (4.46), 95% CI 22.9
      to 40.8. There was a significant difference in the mean value for SR between the
      two groups (P << 0.001). CONCLUSIONS: Capnography may be used as a means of
      continuous respiratory monitoring in non-intubated acutely ill patients.
      Capnogram analysis may be used to indicate airway obstruction in these patients.
      Further work is required to correlate curve indices to degree of airway
      obstruction.

PMID- 9248909
TI  - Bilateral humeral head fractures following an electric shock.

PMID- 9248910
TI  - Axillary brachial plexus block--an underused technique in the accident and
      emergency department.
AB  - OBJECTIVE: To compare axillary brachial plexus block and Bier's block as methods
      of providing upper limb anaesthesia. METHODS: Axillary brachial plexus or Bier's
      blocks were performed on all patients requiring upper limb anaesthesia in a three
      month period. For Bier's block, a single cuff tourniquet and 3 mg/kg 0.5%
      prilocaine were used. For axillary plexus block, 40 ml 1% lignocaine with
      adrenaline (1:200,000) were used, given by perivascular or transarterial
      technique. Prospective analysis was made of time to complete limb anaesthesia,
      type of procedure performed, and duration of limb anaesthesia. Patient perception
      of analgesia and satisfaction with the method of anaesthesia was assessed using a
      10 point visual analogue scale. RESULTS: 75 patients underwent procedures
      requiring upper limb anaesthesia; 39 received axillary plexus block and 36 Bier's
      block. 72% of Bier's blocks and 77% of axillary plexus provided complete
      anaesthesia without the need for supplemental analgesia. The median time to onset
      of anaesthesia was 10 min for Bier's block and 32.5 min for axillary block (P <
      0.001). The median duration of anaesthesia was 15 min for Bier's block and 240
      min for axillary block (P < 0.001). Mean scores for analgesia were 9.7 for
      axillary blocks and 8.8 for Bier's block (P < 0.001). 87% of the axillary block
      group were completely satisfied with the method of anaesthesia, compared with 56%
      of the Bier's block group. CONCLUSIONS: Brachial plexus blocks are an alternative
      form of providing upper limb anaesthesia in the accident and emergency
      department. They are relatively simple to perform, well tolerated by patients,
      and have the advantage of providing prolonged analgesia without the need for
      additional medication.

PMID- 9248911
TI  - A pilot study to assess the sensitivity and specificity of an intrasound device
      in the diagnosis of ankle fractures.
AB  - OBJECTIVE: To investigate the use of a simple intrasound device in the detection
      of malleolar fractures in the accident and emergency (A&E) department. METHODS:
      Patients aged 16 to 70 years with ankle injuries presenting within 24 hours were
      considered for inclusion in the study. Those patients with bony tenderness,
      inability to weight bear, and swelling were examined with a simple intrasound
      device before x-ray examination. A positive result of discomfort, pain,
      withdrawal response, or combinations or these was noted. RESULTS: The device had
      a sensitivity of 85% and a specificity of 52% in detecting malleolar fractures.
      CONCLUSIONS: The use of intrasound in the detection of malleolar fractures cannot
      be relied upon alone, but it may help to limit the number of x rays taken
      unnecessarily. A further study is proposed to confirm these findings.

PMID- 9248912
TI  - Administration of medicines by emergency nurse practitioners according to
      protocols in an accident and emergency department.
AB  - OBJECTIVE: To present the legal and professional issues related to nurse
      administration of drugs according to protocols, and describe the implementation
      and initial audit findings of such a scheme. SETTING: Accident and emergency
      (A&E) department of a district general hospital. METHODS: Analysis of legal and
      professional opinion. Protocols acceptable to the medical, nursing, and pharmacy
      professions were developed across a wide range of drugs appropriate for
      administration by accident and emergency nurse practitioners (ENPs). The first
      six months of the scheme were audited. Audit initially addressed general
      compliance with protocols and later the specific areas of tetanus immunisation
      and emergency contraception. RESULTS: ENPs assessed 2925 patients in six months
      (10.9% of all new patients); 455 patients (15.5% of the ENP patients) were given
      drugs according to protocols. There were no breaches of the protocols. Subsequent
      audit of tetanus immunisation showed 94-100% compliance with protocol standards
      and 71-100% compliance for emergency contraception. CONCLUSIONS: There are no
      legal or professional obstacles to the development of protocols for the
      administration of drugs to patients by nurses without reference to a doctor,
      providing the protocols meet all the requirements of the UKCC and have the
      support of consultant medical staff. Such a system must be subject to regular
      audit to promote a dynamic approach to protocols and training. The system safely
      enhanced the quality of care of patients treated by ENPs in A&E.

PMID- 9248913
TI  - Head injury instructions: a time to unify.
AB  - OBJECTIVE: To compare and contrast the head injury advice give by various
      hospitals in England after minor head injury, and to draw attention to the need
      for a national set of head injury instructions. METHODS: 50 accident and
      emergency departments were contacted by post and asked to supply a copy of their
      head injury information card or leaflet; 41 hospitals replied (82%). RESULTS:
      Comparison of the cards showed inconsistencies and conflicting advice given by
      the departments contacted. CONCLUSIONS: There is a need for a national head
      injury card and a proposal for such a card is presented.

PMID- 9248914
TI  - School accidents to children: time to act.
AB  - OBJECTIVE: To describe the profile of injuries sustained by children in school
      accidents and suggest preventive measures. DESIGN: A five month prospective study
      of children attending an urban accident and emergency (A&E) department. SUBJECTS:
      500 children who sustained injuries in school due to a variety of activities.
      RESULTS: 10 and 12 year old pupils suffered most injuries in school
      grounds/playgrounds, on concrete, or on grass/soil surfaces due to random
      activities resulting in striking or being struck by objects/persons, tripping or
      slipping, and sports (mainly football); 65.5% of these activities were not
      supervised and 67.4% occurred "out of lessons"; 22% sustained fractures or
      dislocations, 28.2% needed follow up treatment, and 1.4% were admitted.
      CONCLUSIONS: Injuries to children in school are a cause for concern. Effective
      preventive measures should concentrate on (a) specific target areas using schemes
      based on individual school, and (b) establishing a credible system of monitoring
      of their effectiveness.

PMID- 9248915
TI  - A review of 105 negligence claims against accident and emergency departments.
AB  - OBJECTIVE: To examine 105 successive negligence claims against NHS accident and
      emergency (A&E) departments in the United Kingdom and to highlight risk
      management points. METHODS: A systematic review of sociodemographic, clinical,
      and legal issues was conducted on each claim. RESULTS: 54 claims involved the
      missed diagnosis of a fracture because of failure to x ray or to interpret the
      films correctly; 27 claims alleged a missed or delayed diagnosis other than
      fracture and were mainly due to incomplete clinical examination or failure to x
      ray or to interpret the films correctly; 24 claims alleged clinical mismanagement
      in the A&E department; in 82 claims (78%) an SHO was allegedly responsible for
      the mistake. By the end of August 1996, 92 claims (87.6%) had been closed, of
      which 38 had been settled out of Court and 54 had not been pursued by the patient
      after disclosure of the records and--where appropriate--a repudiation of
      liability. Of the 13 claims remaining open, seven are considered to be defensible
      and six will have to be settled. CONCLUSIONS: SHOs employed in A&E departments
      need careful training and supervision, with ready access to senior medical
      advice, both clinical and radiological. Most errors leading to claims appear in
      retrospect to have been simple failures of history taking, physical examination,
      interpretation of radiographs, and communication. Poor quality notes imply
      substandard care. About half the claims were found to be indefensible.

PMID- 9248916
TI  - Ichthyosarcotoxism: poisoning by edible fish.

PMID- 9248917
TI  - Traumatic pericardial tamponade: relearning old lessons.
AB  - Traumatic pericardial tamponade is a serious and rapidly fatal injury. As
      penetrating chest wounds are becoming more common, early diagnosis of tamponade
      is important so that life saving treatment can be started. The classical features
      of tamponade may be modified by hypovolaemia and the presence of associated
      injuries; acute tamponade may also be precipitated by rapid administration of
      large volumes of fluid. Pericardiocentesis, while sometimes life saving, is
      dangerous and of limited value. Echocardiography is limited by availability and
      operator dependence. A high degree of clinical suspicion in patients with chest
      injuries, together with close monitoring and reevaluation, particularly during
      volume replacement, is essential. Four cases are described which presented to the
      accident and emergency department of Glasgow Royal Infirmary, in three of which
      there was a significant delay in the diagnosis.

PMID- 9248918
TI  - Back from the dead: extracorporeal rewarming of severe accidental hypothermia
      victims in accident and emergency.
AB  - Severe accidental hypothermia in an urban environment is usually associated with
      drug or alcohol abuse or serious illness in elderly or debilitated patients. In
      the presence of cardiovascular instability, extracorporeal rewarming by
      cardiopulmonary bypass is the gold standard of treatment of such patients. Three
      cases of profound hypothermia with circulatory collapse are presented. Each was
      successfully resuscitated to a full neurological recovery using this method in an
      accident and emergency (A&E) department, although one died later of respiratory
      complications. All three cases had a serum potassium in the normal range at the
      start of treatment. Where facilities exist, extracorporeal rewarming can be
      performed in A&E for patients with profound hypothermia and circulatory collapse.
      Cardiopulmonary resuscitation must be continued throughout the rewarming process.

PMID- 9248919
TI  - Unusual pattern of injury caused by a pyrotechnic hand held signal flare.
AB  - The case is reported of a man shot with a distress flare from a range of about 3
      m. The flare caused a large cavity deep in the pectoral muscles. There should be
      a high index of suspicion about the extent of the injury in all types of
      penetrating trauma.

PMID- 9248920
TI  - Gamma hydroxybutyrate--a coma inducing recreational drug.
AB  - The effects of gamma hydroxybutyrate, a coma inducing recreational drug, are
      described and illustrated by case reports of five patients presenting to accident
      and emergency (A&E). All had depressed levels of consciousness. There was strong
      circumstantial evidence of gamma hydroxybutyrate ingestion in all cases, and
      laboratory evidence in two. All recovered and supportive treatment. gamma
      Hydroxybutyrate has become a fashionable recreational drug. The majority of
      people who have ingested it will recover spontaneously without long term sequelae
      but its toxic effects may be dramatic while they last, particularly when it is
      taken with other drugs or alcohol.

PMID- 9248921
TI  - Pneumococcal pericarditis presenting as an out of hospital cardiopulmonary
      arrest.
AB  - Serious complications of pneumococcal pneumonia have become uncommon with
      effective antibiotic treatment. Purulent pericarditis is a rare though well
      described complication of untreated pneumococcal sepsis. A case of untreated
      pneumococcal pneumonia complicated by purulent pericarditis is described. This
      presented as an out of hospital asystolic cardiopulmonary arrest.

PMID- 9248922
TI  - Conversion disorder presenting as a head injury.
AB  - A case of a conversion disorder which presented as a head injury is described.
      This is a rare problem and by definition a diagnosis of exclusion.

PMID- 9248923
TI  - Obstacles to research in A&E.

PMID- 9248924
TI  - The groin cannula: effective pain relief for fractured neck of femur.

PMID- 9248925
TI  - Emergency medicine training in Australia.

PMID- 9248926
TI  - Unusual complication of interhospital transfer.

PMID- 9248927
TI  - Telephone survey of Diftavax use at school leaving age.

PMID- 9248928
TI  - Out of wedlock births: what do the statistics really mean?

PMID- 9248929
TI  - Alcohol availability and motor vehicle fatalities.

PMID- 9248930
TI  - One method for assessing HIV/AIDS peer-education programs.
AB  - This study offers a new evaluation methodology for peer-education programs. Peer
      educators' knowledge, self-esteem, peer pressure, and the number of friends,
      neighbors, and relatives given HIV/AIDS information were compared before and
      after training using self-administered questionnaires. Significant changes were
      observed in knowledge, peer pressure, self-efficacy, numbers of people given
      condoms, number of formal and informal HIV/AIDS presentations, and numbers of
      HIV/AIDS discussions with friends and neighbors.

PMID- 9248931
TI  - High prevalence of Chlamydia trachomatis infections in adolescent females not
      having pelvic examinations: utility of PCR-based urine screening in urban
      adolescent clinic setting.
AB  - PURPOSE: To determine utility of polymerase chain reaction (PCR)-based urine
      screening for Chlamydia trachomatis in the care of adolescent females in an urban
      clinic. METHODS: Females > or = 15 years of age attending an adolescent clinic
      were approached consecutively. Each enrollee was interviewed to determine the
      primary reason(s) for the clinic visit and was queried about genitourinary
      symptoms. Nonsterile voided urine specimens were tested for C. trachomatis using
      PCR-based analysis. Endocervical C. trachomatis cultures were obtained from the
      subjects who had a pelvic examination. Main outcome measures were chlamydia
      infection rates in clinic attendees whether a pelvic examination was performed or
      not. RESULTS: A total of 315 (99.4%) of 317 patients approached agreed to
      participate. Overall, 47 (14.9%) patients had positive urine PCR tests. The
      chlamydia infection rate detected by urine PCR was 22.1% (19 of 86) among those
      who had pelvic examinations performed and 12.2% (28 of 229) among those who did
      not (p = .03; odds ratio 2.04; 95% confidence interval 1.02, 4.06). Sixty percent
      (28 of 47) of chlamydia infections identified during the study period were
      identified by the urine screening test. CONCLUSION: Urine screening was accepted
      by vast majority of female adolescents attending the clinic irrespective of
      reason for the clinic visit, and was highly effective in identifying unsuspected
      C. trachomatis infections, particularly among girls attending the clinic for
      reasons unrelated to reproductive health care and as an interim screening tool
      for adolescent family-planning clients.

PMID- 9248932
TI  - On the need to screen for Chlamydia and gonorrhea infections prior to colposcopy
      in adolescents.
AB  - PURPOSE: The purposes of this study were to explore the association of pelvic
      inflammatory disease (PID) with cervical biopsy and to examine whether screening
      for Chlamydia and gonorrhea infections within 2 weeks prior to colposcopy is a
      standard clinical practice among adolescents' care providers in the United
      States. METHODS: An anonymous questionnaire was distributed to U.S. physicians
      and nurses who are members of the Society for Adolescent Medicine, and/or the
      North American Society for Pediatric and Adolescent Gynecology. RESULTS: A total
      of 368, from all the states in America, responded. Only 5% of the respondents
      have encountered biopsy-associated PID owing to Chlamydia and/or gonorrhea. The
      incidence rate of biopsy-associated PID reported by the respondents to this
      survey was approximately 1:1000 colposcopic biopsies. Fifteen percent of the
      respondents screen their adolescent patients, and 23% favor screening for
      Chlamydia and gonorrhea infections within 2 weeks prior to colposcopy. Previous
      experience with colposcopy and previous encounters with biopsy-associated PID in
      adolescents did not significantly affect the practice or the opinion of the
      respondents. CONCLUSIONS: Screening for Chlamydia and gonorrhea infections within
      2 weeks prior to colposcopy in adolescents is presently not a common clinical
      practice among U.S. adolescents' care providers. Because of the potential risk of
      biopsy-associated PID, it is advisable to minimize the interval between Chlamydia
      and gonorrhea screening and colposcopy in adolescents.

PMID- 9248933
TI  - Are adolescents accurate in self-report of frequencies of sexually transmitted
      diseases and pregnancies?
AB  - PURPOSE: Many surveys of adolescent behavior are dependent on self-reported data.
      We sought to assess the accuracy of adolescent self-report of sexually
      transmitted diseases (STDs) and pregnancies. METHODS: We randomly selected 149
      (118 females, 31 males) adolescents to participate in this accuracy study. Follow
      up questionnaires were administered to the 126 patients (99 females, 27 males)
      who returned after enrollment. Patients were asked about STDs and pregnancies
      during the follow-up period which ranged from 6 months to 1 year. All patient
      charts were reviewed to validate post-testing history. RESULTS: Return visits
      were made by 126 patients (84%). Fifty-one (40%) denied having had an STD at all
      during the follow-up period but were found to have had at least one STD. Another
      11 (9%) admitted having had an STD but had multiple STDs in excess of what they
      reported. Only 46% of the patients provided accurate information on the follow-up
      questionnaire. Of the 99 girls who returned for follow-up, the inaccurate
      patients (10%) consisted of 9 who reported no visits for a pregnancy but had a
      pregnancy documented in their charts and 1 who underreported her number of
      pregnancies. Reliability analysis of the accuracy of STD and pregnancy self
      report for our patients showed kappas ranging from 0.185 to 0.413 (slight and
      fair to moderate, respectively). Pearson correlation coefficients were 0.3107 and
      0.4364 for STD and pregnancy, respectively. CONCLUSIONS: Our patients' histories
      of visits for STDs and pregnancies are often not substantiated by review of their
      medical records. The reason for the inaccuracies in self-report of sexual
      behaviors is unclear. Further research in this area should be done. Physicians
      must confirm patient history concerning sexual practices through appropriate
      record review and medical evaluation.

PMID- 9248934
TI  - Tobacco use among male high school athletes.
AB  - PURPOSE: The purpose of this study was to compare tobacco use among high school
      male athletes with their nonathlete counterparts. We hypothesized that there was
      an inverse correlation between the intensity level of the sport and frequency of
      tobacco use. METHODS: Students were surveyed at seven high schools in northwest
      Louisiana using a 109-item questionnaire. Of the 1,200 males tested, 83%
      participated in one or more sports. The mean age was 15.8, and mean grade level
      was 10th. Sixty-seven percent were white, 27% African-American (AA), and 6%
      other. RESULTS: Forty-one percent of the adolescent males tested were one or more
      tobacco products, 31% reported cigarette smoking, 21% chewed tobacco, and 18%
      used snuff. Eleven percent reported using all three tobacco products. Race was a
      significant determinant of tobacco use, with whites being more likely to use each
      of the three tobacco products (P < .001). Medium- and high-intensity athletes
      were significantly (P < .01) less likely to be heavy smokers than athletes
      participating in low-intensity sports and nonathletes. However, athletes of each
      intensity sport used chewing tobacco and snuff at significantly higher rates (P <
      .001) than nonathletes. When race and grade point average were controlled, sports
      intensity was a significant predictor of smokeless tobacco use but not overall
      smoking behavior. Both AA and white high school male athletes at all sport
      intensity levels were using chewing tobacco and snuff at a rate higher at least
      1.5 times that of their nonathlete counterparts. CONCLUSIONS: In our study, high
      school males' sports participation was a predictor of smokeless tobacco use but
      not overall smoking behavior. Although the probability of AA high school athletes
      using smokeless tobacco was low compared to whites, the pattern of use was
      similar across intensity levels of sports.

PMID- 9248935
TI  - Adolescents with factitious HIV disease.
AB  - PURPOSE: To describe two cases of factitious HIV disease and their implications
      for clinical practice and research. METHODS: Review of medical records and
      literature search. RESULTS: A 19-year-old female and 17-year-old male were
      referred to an adolescent HIV clinic for evaluation and treatment of HIV disease.
      The former reported having been tested at a primary care clinic because of her
      history of transfusions, although the likely route of infection was intravenous
      drug use. The 17-year-old claimed to have contracted HIV through unprotected
      vaginal intercourse. Both patients reported HIV-related symptoms and prior
      seropositive HIV antibody test results which could not be corroborated. Other
      important features were histories of mental health problems, lack of apparent
      distress regarding HIV infection, and extensive knowledge of HIV disease.
      CONCLUSIONS: In both cases, the most likely diagnosis was Factitious Disorder
      with combined psychological and physical signs and symptoms, based on the
      feigning of seropositive HIV test results, report of physical symptoms
      undocumented by physical examination, the need to assume the sick role, and the
      absence of obvious secondary gain. This report serves to underscore the need to
      confirm the presence of HIV infection in young people who seek treatment for HIV
      disease, especially when clinical presentations resemble these cases.

PMID- 9248936
TI  - Predicting the stages of smoking acquisition according to the theory of planned
      behavior.
AB  - PURPOSE: The goal of the present study was to determine the variables from the
      theory of planned behavior that are responsible for differentiating the stages of
      smoking acquisition. METHODS: A self-administered questionnaire was distributed
      to 360 secondary I level students from a possible population of 500 students.
      This questionnaire was designed by the researchers according to Ajzen and
      Fishbein's and Ajzen's recommendations regarding the predictive model variables.
      It also contained sociodemographic and personal variables. Data from this cross
      sectional study were analyzed using multivariate analysis. RESULTS: The
      multivariate analysis of variance indicated an overall significant difference in
      terms of the three psychosocial variables (Pillais approximation F12,867 = 25.22;
      p < or = 0.000). The analyses of variance showed that the variables attitude
      (F4,289 = 112.25; p = 0.0001), subjective norm (F4,289 = 23.48; p = 0.0001), and
      perceived behavioral control (F4,289 = 87.92; p = 0.0001) contributed to
      differentiating the stages of smoking acquisition. The discriminant function
      analysis indicated that attitude (0.826) and perceived behavioral control (0.725)
      dominate the construct; the contribution of the subjective norm (0.375) is less
      important. Finally, these variables from the theory of planned behavior permitted
      the correct classification of 68.4% of adolescents into the stages of smoking
      acquisition. CONCLUSION: The application of the theory of planned behavior seems
      to increase understanding of the stages of smoking acquisition. The distribution
      of students in the five stages shows that in the advanced stages, refraining from
      smoking is more difficult, and that smoking advantages surpass disadvantages.
      These findings represent only a step toward the development of interventions
      aimed at warning adolescents against smoking.

PMID- 9248937
TI  - Problems in conceptualizing adolescent risk behaviors: international comparisons.

PMID- 9248938
TI  - Double suicide attempt among adolescents.

PMID- 9248939
TI  - Verification of exposure to sulfur mustard in two casualties of the Iran-Iraq
      conflict.
AB  - The exposure of two Iranian victims of the Iran-Iraq conflict (1980-1988) to
      sulfur mustard was established by immunochemical and mass spectrometric analysis
      of blood samples taken 22 and 26 days after alleged exposure. One victim suffered
      from skin injuries compatible with sulfur mustard intoxication but did not have
      lung injuries; the symptoms of the other victim were only vaguely compatible with
      sulfur mustard intoxication. Both patients recovered. Immunochemical analysis was
      based on detection of the N7-guanine adduct of the agent in DNA from lymphocytes
      and granulocytes, whereas the N-terminal valine adduct in globin was determined
      by gas chromatography-mass spectrometry after a modified Edman degradation. The
      valine adduct levels correspond with those found in human blood after in vitro
      treatment with 0.9 microM sulfur mustard.

PMID- 9248941
TI  - Distribution of codeine, morphine, and 6-acetylmorphine in vitreous humor.
AB  - Two hundred and twenty-three vitreous humor specimens, which were obtained from a
      medical examiner's office, were found to be opiate positive (cutoff, 50 ng/mL) by
      fluorescence polarization immunoassay. All samples were analyzed for their free
      codeine, morphine, and 6-acetylmorphine contents by a gas chromatography-mass
      spectrometry protocol. 6-Acetylmorphine was found (cutoff, 10 ng/mL) in 41
      specimens in the concentration range of 10-125 ng/mL. Twenty specimens had a free
      codeine-free morphine concentration ratio > or = 1. Eighty-five samples that were
      found to contain 50 ng/mL free morphine were further analyzed for their total
      codeine and total morphine contents. Total codeine-total morphine concentration
      ratios in 8 (of the 85 samples) were > or = 1, whereas this ratio in the others
      (only those with a codeine concentration high than 15 ng/mL were included) was
      significantly lower than 1. The codeine-morphine concentration ratio in vitreous
      humor appears to resemble that reported for blood and urine and can be used as
      the basis for differentiating between codeine- and morphine- (heroin-) induced
      fatalities.

PMID- 9248940
TI  - Determination of naltrexone and 6-beta-naltrexol in plasma by solid-phase
      extraction and gas chromatography-negative ion chemical ionization-mass
      spectrometry.
AB  - Solid-phase extraction (SPE) and a one-step derivatization are combined with gas
      chromatography-negative ion chemical ionization-mass spectrometry to simplify a
      previously reported method for the determination of naltrexone and its
      metabolite, 6-beta-naltrexol, in human plasma. Deuterated isotopomers of
      naltrexone and 6-beta-naltrexol are used as internal standards. After SPE, the
      extracts are derivatized with pentafluoropropionic anhydride at room temperature
      to form predominantly the bispentafluoropropionyl derivative of naltrexone and
      the trispentafluoropropionyl derivative of 6-beta-naltrexol. The derivatized
      extracts are analyzed by monitoring ion currents at m/z 633 (naltrexone), m/z 636
      (naltrexone-2H3), m/z 633 6-beta-naltrexol), and m/z 640 (6-beta-naltrexol-2H7).
      Control plasma samples containing 0.3, 3, or 30 ng/nl of each analyte were
      analyzed for precision and accuracy with the following results: intra-assay, the
      percentage of target concentrations were 107-113% for naltrexone and 107-120% for
      6-beta-naltrexol, and the coefficients of variation (CVs) were 3.1-6.3% for
      naltrexone and 3.1-5.7% for 6-beta-naltrexol; interassay, the percentage of
      target concentrations were 103-110% for naltrexone and 110-113% for 6-beta
      naltrexol, and the CVs were 6.1-9.1% for naltrexone and 5.9-9.1% for 6-beta
      naltrexol. At the limit of quantitation (LOQ) of 0.1 ng/ml, both analytes
      quantified within 20% of the target concentration with CVs less than 17%. The
      extraction recoveries determined at 0.3 and 30 ng/ml were 79 and 80% for
      naltrexone and 76 and 75% for 6-beta-naltrexol. Bench-top stability tested with
      concentrations of 0.3 and 3.0 ng/ml did not decrease more than 10% from the zero
      hour controls at 3, 6 and 24 h. Selectively was determined using plasma from six
      donors and none showed interfering peaks greater than 22% of the LOQ for
      naltrexone and 53% of the LOQ for 6-beta-naltrexol. Using this method, naltrexone
      and 6-beta-naltrexol were readily detected in plasma specimens collected 5.5 h
      after oral doses of 25 or 100 mg naltrexone. Following discontinuation of
      treatment, naltrexone was detected 30 h after the 100-mg dose, whereas 6-beta
      naltrexol was detected 125 h after both the 25- and 100-mg doses.

PMID- 9248942
TI  - Analytical methods for the determination of urinary 2,4-dichlorophenoxyacetic
      acid and 2-methyl-4-chlorophenoxyacetic acid in occupationally exposed subjects
      and in the general population.
AB  - Two methods for the quantitative analysis of 2,4-dichlorophenoxyacetic acid (2,4
      D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) in urine were compared. The
      first was an high-performance liquid chromatography method using a C8 column with
      ion suppression and diode array detection. The urine extracts were first purified
      by solid-phase extraction (SPE) on silica capillary columns. The detection limit
      of the method was 15 micrograms/L for both compounds. The percentage coefficient
      of variation of the whole analysis evaluated at a concentration of 125.0
      micrograms/L was 6.2% for 2,4-D and 6.8% for MCPA. The mean recovery of analysis
      was 81% for 2,4-D and 85% for MCPA. The second was a gas chromatographic (GC)
      method in which the compounds were first derivatized with
      pentafluorobenzylbromide to pentafluorobenzyl esters, which were determined with
      a slightly polar capillary column and electron capture detection. Before GC
      analysis, the urine extracts were purified by SPE on silica capillary columns.
      This method had a detection limit of 1 microgram/L for both compounds and a
      percentage coefficient of variation of the whole analysis, evaluated at a
      concentration of 30.0 micrograms/L, of 8% for 2,4-D, and of 5.5% for MCPA. the
      mean recovery was 87% for 2,4-D and 94% for MCPA. The low detection limit made
      the second method suitable for assaying the two herbicides in the general
      population. Duplicate analysis of ten urine samples from occupationally exposed
      subjects by the two methods gave identical results for a wide range of
      concentrations.

PMID- 9248943
TI  - Simultaneous determination of heroin 6-monoacetylmorphine, morphine, and its
      glucuronides by liquid chromatography--atmospheric pressure ionspray-mass
      spectrometry.
AB  - A new analytical technique has been developed for the simultaneous determination
      of heroin, 6-monoacetylmorphine, morphine, morphine-6- and 3-glucuronides, and
      codeine in serum using liquid chromatography coupled with ionspray mass
      spectrometry. The analytes and the internal standard, nalorphine, were subjected
      to solid-phase extraction (SPE) using ethyl SPE columns before chromatography.
      The chromatographic separation of the analytes was achieved using a normal phase
      column and a water-methanol-acetonitrile-formic acid mobile phase at a flow rate
      of 230 microL/min. The mass spectrometer was operated in selected-ion monitoring
      mode. Under these conditions, the limit of quantitation was 0.5 ng/ml for heroin,
      4 ng/ml for 6-monoacetylmorphine, 4 ng/ml for morphine, 1 ng/ml for morphine-3
      glucuronide, 4 ng/ml for morphine-6-glucuronide, and 4 ng/mL for codeine. Serum
      levels of heroin metabolites were determined in C57BL/6 inbred mice after a dose
      of 20 mg/kg heroin administered subcutaneously. 6-monoacetylmorphine showed a
      peak concentration of 0.93 micrograms/mL serum at 3 min, whereas morphine and
      morphine-3-glucuronide achieved their peak concentrations of 9.6 and 2.9
      micrograms/mL serum at 10 and 20 min, respectively. Finally, the absence of
      morphine-6-glucuronide and codeine excluded the possibility of their formation
      from morphine in this animal model.

PMID- 9248944
TI  - Solid-phase extraction in amphetamine and methamphetamine analysis of urine.
AB  - A systematic evaluation that compares the recoveries of methamphetamine and
      amphetamine from spiked urine using C8, C18, strong cation exchanger (SCX), and
      C8-SCX mixed procedures (solid-phase extraction) is reported. Optimized
      experimental conditions including pH of the sample, solvent composition, and
      urine concentration for different solid-phase extraction sorbents were studied.
      The largest recoveries--greater than 86% for methamphetamine and greater than 88%
      for amphetamine--were achieved with a mixed adsorbent (C8-SCX) and mixed elution
      solvent CH2Cl2-i-propanol-NH4OH (78:20:2) at pH 6. The concentration of the urine
      matrix did not affect the extraction efficiency. The detection limits of
      methamphetamine and amphetamine in urine were obtained at 0.03 and 0.07
      micrograms/mL, respectively, using gas chromatographic-mass spectrometric
      analysis operated in the electron impact mode.

PMID- 9248945
TI  - A positive cannabinoids workplace drug test following the ingestion of
      commercially available hemp seed oil.
AB  - A commercially available health food product of cold-pressed hemp seed oil
      ingested by one volunteer twice a day for 4 1/2 days (135 mL total). Urine
      specimens collected from the volunteer were subjected to standard workplace urine
      drug testing procedures, and the following concentrations of 11-nor-delta9-
      tetrahydrocannabinol carboxylic acid (9-THCA) were detected: 41 ng/mL 9-THCA at
      45 h, 49 ng/mL at 69 h, and 55 ng/mL at 93 h. Ingestion was discontinued after 93
      h, and the following concentrations were detected: 68 ng/mL at 108 h, 57 ng/mL at
      117 h, 31 ng/mL at 126 h, and 20 ng/mL at 142 h. The first specimen that tested
      negative (50 ng/mL initial immunoassay test, 15 ng/mL confirmatory gas
      chromatographic-mass spectrometric test) was at 146 h, which was 53 h after the
      last hemp seed oil ingestion. Four subsequent specimens taken to 177 h were also
      negative. This study indicates that a workplace urine drug test positive for
      cannabinoids may arise from the consumption of commercially available cold
      pressed hemp seed oil.

PMID- 9248946
TI  - The confirmation of volatiles by solid-phase microextraction and GC-MS in the
      investigation of two traffic fatalities.
AB  - A simple, sensitive, and reliable method was developed for the confirmation of
      nonroutine volatiles in the investigation of two traffic fatalities. Solid-phase
      microextraction (SPME) fibers were used to extract volatile compounds from the
      headspace of sample vials; components were subsequently analyzed by gas
      chromatography-mass spectrometry (GC-MS). In the first case, ethanol and
      methylene chloride were detected in a urine sample by headspace SPME and GC-MS.
      The second case involved the analysis of volatile petroleum products from
      submitted specimens by headspace SPME and GC-MS. In both cases, SPME and GC-MS
      analyses provided crucial evidence in the investigation of the traffic
      fatalities.

PMID- 9248947
TI  - Hair analysis for drugs of abuse. XVI. Disposition of fenethylline and its
      metabolite into hair and discrimination between fenethylline use and amphetamine
      use by hair analysis.
AB  - The incorporation tendency of fenethylline (FNT) and its metabolite into rat hair
      and the discrimination between FNT use and amphetamine (AP) use by hair analysis
      using gas chromatography-mass spectrometry with selected ion monitoring are
      described. After the intraperitoneal administrations of FNT to pigmented hairy
      rats (5 mg/kg/day, 10 days, n = 3), concentrations of FNT and its metabolite, AP,
      in the rat hair newly grown over 4 weeks were compared with area under the
      concentration versus time curves (AUCs) of the drugs in the rat plasma. The hair
      concentrations of FNT and AP were 52 +/- 1.4 and 4.9 +/- 0.6 ng/mg, whereas those
      of plasma AUCs were 55.9 +/- 23.1 and 22.3 +/- 4.9 micrograms.min/mL,
      respectively. The ratios of the hair concentrations to the AUCs of FNT tends to
      be highly incorporated into hair from suggests that FNT tends to be highly
      incorporated into hair from blood. The analytical method was applied to the
      determination of the metabolites in scalp hair of humans who were given FNT
      orally in multiple doses (50 mg/day, 3 days, n = 5) or in a single dose (50
      mg/day, 1 day, n = 1). FNT and AP were detected at 0.51 +/- 0.23 and 0.35 +/-
      0.12 ng/mg, respectively, in the proximal 1-cm hair segments from subjects given
      FNT orally for 3 days and 0.25 and 0.11 ng/mg, respectively, in the single-dose
      sample. In addition, it was found that the concentrations of FNT were 1.2 to 2.7
      times greater than those of AP in the human hair samples, except for one sample,
      although FNT rapidly disappeared from the urine compared with AP. It was
      concluded that hair would be a good specimen for disclosure of drug history of
      FNT and for discrimination between FNT use and AP abuse.

PMID- 9248948
TI  - Development of a supercritical fluid extraction method for the determination of
      temazepam in whole blood.
AB  - A supercritical fluid extraction (SFE) procedure for the analysis of temazepam
      from whole blood was developed. Quantitative recoveries were obtained by high
      performance liquid chromatography using prazepam as an internal standard and
      carefully monitoring the extraction temperature and pressure. The results were
      found to compare well with those obtained by solid-phase extraction techniques,
      but they also had the advantages of reduced solvent consumption and minimal
      sample handling. The application of this method to authentic forensic blood
      specimens showed the SFE method to be useful as an alternative procedure for the
      extraction of temazepam in the toxicology laboratory.

PMID- 9248949
TI  - Determination of methocarbamol in equine serum and urine by high-performance
      liquid chromatography with ultraviolet detection and atmospheric pressure
      ionization-mass spectrometric confirmation.
AB  - Urine and serum samples collected from four standard-bred mares after and oral
      regimen administration of methocarbamol were extracted and analyzed. The method
      consisted of enzyme hydrolysis followed by a one-step liquid-liquid extraction,
      separation on a reversed-phase (RP-18) column, and detection using an ultraviolet
      (UV) detector. The confirmation was carried out using a liquid chromatography
      atmospheric pressure ionization-mass spectrometry (LC-API-MS) system. Maximum
      methocarbamol concentrations of 1498, 1734, 1547, 2322 micrograms/mL in urine and
      4.9, 1.7, and 3.6 micrograms/mL in serum were observed. The peak concentrations
      of the drug were detected 1-4 h (urine) and 10-60 min (serum) after
      administration to four horses. The method validation results and drug elimination
      profiles for both urine and serum are presented and discussed.

PMID- 9248950
TI  - A simple, rapid gas-liquid chromatographic procedure for the determination of
      valproic acid in serum.
AB  - A simple, rapid method for the gas-liquid chromatographic (GLC) determination of
      valproic acid in serum without prior derivatization on a Nukol wide-bore
      capillary column is presented. The method was determined to have a lower limit of
      detection (LOD) of 5 mg/L and a lower limit of quantitation (LOQ) of 10 mg/L; the
      method was linear up to 6000 mg/L. Within-run precision (expressed as percent
      coefficient of variation [CV]) for control specimens containing 60 mg/L and 120
      mg/L was 4.3% CV (n = 10) and 3.0% CV (n = 10), respectively. The between-run
      precision of control sera analyzed over four week yielded 8% at 25 mg/L, 5% at 60
      mg/L, and 3% at 120 mg/L. The absolute, uncorrected, analytical recoveries of
      valproic acid at 10, 32, and 120 mg/L were 97% (n = 5), 101% (n = 5), and 84% (n
      = 5), respectively. The absolute recovery of the internal standard was 97% (n =
      9). Drugs commonly indicated for therapeutic monitoring and other serum
      constituents were found not to interfere with the procedure. The results of an
      intermethod comparison study of serum specimens analyzed by TDx immunoassay
      versus the presented GLC method demonstrated good correlation. At 95% confidence
      limits, no statistically significant differences were observed between results (p
      < 0.05). The method is particularly advantageous to toxicology laboratories
      because chromatography is performed on a polar GLC column that can be modified
      readily for the routine clinical analysis of other polar compounds such as
      ethylene glycol and other glycols.

PMID- 9248951
TI  - Postmortem distribution of nicotine and cotinine from a case involving the
      simultaneous administration of multiple nicotine transdermal systems.
AB  - A 31-year-old female was found dead with 18 nicotine transdermal system patches
      taped to her upper body and a plastic bag taped over her nose and mouth (the
      cause of death was ruled asphyxiation). Nicotine concentrations in biological
      fluids and tissues were analyzed using a liquid-liquid extraction followed by
      injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen
      phosphorus detector. Cotinine was separated from the biological matrices using
      solid-phase extraction followed by analysis on an HP-5890 GC with flame
      ionization detection. A variety of specimens were analyzed, including blood,
      urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood
      concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times,
      respectively, the mean C(max) value reported following the proper administration
      of a single 7-mg/day patch.

PMID- 9248952
TI  - HPLC-DAD and HPLC-MS findings in fatality involving (Z)-cis-clopenthixol
      (zuclopenthixol).
AB  - A fatality that was due to massive ingestion of the thioxanthene neuroleptic (Z)
      cis-clopenthixol (zuclopenthixol, Z-CPT) is described. The total toxicological
      screening and the quantitation of both the ingested drugs and its inactive isomer
      (E)-trans-clopenthixol (E-CPT, produced by in vivo isomerization) in postmortem
      fluids and viscerae were produced by high-performance liquid chromatography
      (HPLC)-diode array detection. Drug confirmation was carried out by HPLC-mass
      spectrometry with an ionspray interface. Although death occurred 40 h after the
      drug intake, postmortem blood concentrations were 391 and 275 mg/mL for Z-CPT and
      E-CPT, respectively (50 to 100 times the usual therapeutic values). The cause of
      death was suicide, and the manner was acute neuroleptic overdosage.

PMID- 9248953
TI  - A positive THC urinalysis from hemp (Cannabis) seed oil.

PMID- 9248954
TI  - Relevance of toxicological screening for chloroquine in nonmalarious areas.

PMID- 9248955
TI  - Accidental death due to inhalation of butane.

PMID- 9248956
TI  - In-vitro antimicrobial susceptibility testing: does it really matter?

PMID- 9248957
TI  - What's the use of susceptibility testing?
AB  - The need for routine antibiotic susceptibility testing is not self-evident. Much
      infection, particularly that seen in domiciliary practice can be (and is)
      adequately treated on an empirical basis. Although the collection of
      susceptibility data for the purposes of monitoring antibiotic resistance trends
      is a useful by-product of routine testing, this could be effectively carried out
      by periodic surveys designed for the purpose. Nonetheless, there remain many
      circumstances in which laboratory testing of antibiotic susceptibility
      contributes directly to patient care, and some in which it is indispensable. An
      important additional consideration is that the activities and expertise of the
      microbiology laboratory can have a powerful influence on antibiotic usage, and
      hence on the pressures that facilitate the emergence of antimicrobial drug
      resistance.

PMID- 9248958
TI  - Standardization of susceptibility testing methods.
AB  - Standardization of antibiotic susceptibility tests is desirable but faces several
      problems. Despite considerable effort, it has been impossible to devise an ideal
      medium, and discussion continues as to the best inoculum, disk content,
      atmosphere of incubation, method of reading results, and interpretation of those
      results in both microbiological and clinical contexts. A range of methods, from
      manual to almost completely automated, is in current use. Some microbiologists,
      especially those who use NCCLS methods, advocate the universal adoption of one
      method for each type of manual test--agar dilution, broth dilution or agar
      diffusion. Others accept diversity, believing that strict adherence to protocols
      will make it possible for the results obtained by one method--though not
      necessarily their interpretation--to be super-imposed on those obtained by other
      methods.

PMID- 9248959
TI  - Susceptibility testing of fungi and correlation with clinical outcome.
AB  - With recent developments in the field of mycology such as increased incidence of
      fungal infections, the introduction of newer, safer antifungals, and the
      emergence of resistance, the need for clinically relevant antifungal
      susceptibility testing methods is obvious. Studies performed over the past decade
      have allowed the NCCLS Subcommittee on Antifungal Testing to achieve consensus on
      a new standardized broth dilution method for in vitro susceptibility testing of
      yeast (NCCLS M27). This review summarizes the studies correlating in vitro
      susceptibility testing and clinical outcome, presents tentative breakpoints for
      fluconazole and itraconazole, and emphasizes the utility of in vitro testing in
      the management of patients with candidiasis.

PMID- 9248960
TI  - Problems arising in antimicrobial therapy due to false susceptibility testing.
AB  - In vitro antibiotic susceptibility testing provides clinicians with guidelines to
      assess microbial sensitivities to various antibiotics. However, susceptibility
      testing is a laboratory procedure which does not always reflect the in vivo
      situation. False susceptibility testing is often due to methodological/disk
      concentration problems. In vitro versus in vivo discrepancies may also occur
      because of problems with varying pH/antibiotic concentration at the infection
      site. Clinicians should use susceptibility testing as a guide, but must rely upon
      the patient's clinical response as the ultimate in vivo susceptibility test.

PMID- 9248961
TI  - In vitro antibiotic sensitivity testing breakpoints and therapeutic activity in
      induced infections in animal models.
AB  - Antimicrobial susceptibility breakpoints are artificially designated to classify
      organisms as susceptible, intermediate or resistant but such values may differ
      according to the relative weight given to the microbiological, pharmacological
      and clinical information. Animal models of bacterial infections are considered
      necessary to establish tentative breakpoints before initiating clinical trials in
      humans. Studies in animals provide a preliminary indication of the most effective
      and least toxic concentration of the antibiotic and give a rational basis for the
      selection of dosages and schedules. Animal models of therapeutic efficacy have
      demonstrated the importance of the inoculum effect, showing that the minimum
      inhibitory concentration (MIC) determined with high inoculum (10(7)-10(8) CFU/ml)
      is, under some experimental conditions, a better predictor of therapeutic
      efficacy than the value obtained with standard (10(4)-10(5) CFU/Ml) inoculum.
      Studies in animals have demonstrated the failure of some fluoroquinolones in
      respiratory tract infections where Streptococcus pneumoniae was present or the
      efficacy of penicillins and third-generation cephalosporins for treating
      respiratory tract infections and meningitis by pneumococci with diminished
      susceptibility to such agents. Although most therapeutic models in animals should
      be carried out during preclinical studies, many are done during later phases of
      antibiotic development, as explicate models of what is seen in clinical practice.

PMID- 9248962
TI  - Breakpoints in antibiotic sensitivity testing and their clinical relevance.
AB  - Antibiotic sensitivity testing has been developed into a highly sophisticated
      process technically. Interpretation of results obtained requires the definition
      of breakpoints in order to separate sensitive (likely to respond to treatment)
      from resistant (likely to persist despite treatment) strains. Various methods
      used for the setting of breakpoints are described and their merits and drawbacks
      discussed. Although there may be wide disparities in the definitions adopted in
      different countries, there is no clinical evidence that favours one set of
      figures over another. Problems over determination of breakpoints for fungi and of
      antibiotic combinations remain to be resolved.

PMID- 9248963
TI  - In vitro models for prediction of antimicrobial activity: a pharmacokinetic and
      pharmacodynamic perspective.
AB  - The endpoints associated with conventional susceptibility testing, e.g., the
      minimum inhibitory concentration or minimum bactericidal concentration (MIC or
      MBC), are discrete in nature. These endpoint measurements do not provide any
      information, regarding the pharmacodynamic changes exhibited by the bacteria in
      reaction to the antibiotic activity during the incubation period. Another
      limitation of these susceptibility tests is the maintenance of constant
      antibiotic concentrations; this condition contrasts sharply to the continuously
      changing concentrations observed in vivo. To tackle these problems, various in
      vitro pharmacokinetic/pharmacodynamic models have been developed. Taking into
      consideration various pharmacokinetic determinants, such models allow more
      comprehensive study of the pharmacodynamic effects demonstrated by antibiotics.
      In this paper, the implications and usefulness of these in vitro models to the
      characterization of antimicrobial activity are discussed. Limitations associated
      with their use are also addressed.

PMID- 9248964
TI  - Pharmacodynamics of antimicrobial agents and rationale for their dosing.
AB  - Antimicrobial pharmacodynamics are an area of considerable importance in terms of
      dose regimen optimisation and clinical outcome. The pharmacodynamic properties of
      penicillins, cephalosporins, carbapenems, quinolones, glycopeptides and
      aminoglycosides are reviewed; the impact such knowledge may have in the future on
      how we dose these agents is discussed.

PMID- 9248965
TI  - Pharmacodynamics and the relationship between in vitro and in vivo activity of
      antimicrobial agents.
AB  - This article discusses the various in vitro and in vivo models used to
      investigate the pharmacodynamics of antibiotic action and relates this to
      clinical use of antibiotics. The dosing of beta-lactams is discussed in detail,
      particularly in relation to the method dependence of the various models of post
      antibiotic effect (PAE) and the different morphological forms that are produced
      by different beta-lactams.

PMID- 9248966
TI  - Therapeutic monitoring, the concentration-effect relationship and impact on the
      clinical efficacy of antibiotic agents.
AB  - Therapeutic monitoring is now technically feasible for a wide variety of
      antibiotic agents and data are accumulating on the relationship of blood levels
      and clinical efficacy. For each antibiotic a therapeutic range and dosage regimen
      can be based theoretically on its known pharmacokinetics, pharmacodynamics in
      vitro, and also use in animal and human treatment studies. Antibiotics can be
      characterised into types by their mechanism of kill, as either concentration
      dependent (for which achieving a large post-dose concentration to MIC ratio
      appears important) or concentration-independent/time-dependent (where efficacy is
      related to maintain the overall concentration above the MIC). Hopefully,
      concentration-controlled trials will be performed when new antibiotics are
      introduced, to determine a therapeutic range which correlates with clinical
      efficacy, and so enable monitoring to lead to a more rational approach to
      antibiotic administration.

PMID- 9248967
TI  - In vitro antibiotics testing and its relationship to clinical activity.
AB  - The need for predicting bacteriological and clinical antibiotic activity appeared
      early after development of the first antibiotics. Antimicrobial efficacy is
      significant among many therapeutic management factors, including surgery, drug
      interactions and non-antibiotic therapies. Clinical efficacy is not only related
      to antimicrobial efficacy, but also to host characteristics and causative
      organism attributes. Because all these factors interact to achieve success or
      failure in the management of a given infected patient, to model an n-factor in
      vivo system from n'-factors in vitro may be difficult.

PMID- 9248968
TI  - The prohost effect of antimicrobial agents as a predictor of clinical outcome.
AB  - Apart from their direct antimicrobial activity, some antimicrobial agents may
      interfere in the complex host-microorganism interplay by modulating the natural
      response to invading pathogens. The three main aspects of this non-antibiotic
      effect (alteration of bacterial virulence, synergism with/impairment of the
      natural host response, impact on effector cell progenitors) will be briefly
      reviewed here, along with their potential incidence in the clinical outcome of
      infectious diseases.

PMID- 9248969
TI  - Interactions among antibiotics, bacteria and the human immune system: the
      clinical relevance of in vitro testing.
AB  - The role of interactions of the host immune system with antibacterial activities
      of antibiotics is extremely complex and its analysis is still at an early stage.
      Standard in vitro trests of antibiotic susceptibilities of pathogens provide only
      limited information since they do not take into account either the potential
      interaction of immunomodulating activities of antibiotics in vivo or the
      participation of the host immune response in the infection outcome. The
      understanding of these complex relationships is of major importance in treating
      immunocompromised patients, but this approach is still under investigation and
      much work remains to be done in order to confer more significance on in vitro
      testing.

PMID- 9248970
TI  - The importance of in-vitro susceptibility testing in the management of
      compromised hosts.
AB  - Bacterial infection may be a life-threatening complication in the
      immunocompromised host, especially in the face of profound and persistent
      granulocytopenia induced by cytotoxicity. Under these circumstances, antibiotic
      therapy is started on an empirical basis; however, knowledge of the antibiotic
      susceptibilities of the offending pathogen may represent a useful guide for
      therapy adjustments in individuals who do not respond satisfactorily to initial
      antibiotics. Careful antimicrobial susceptibility testing may also represent the
      first step of epidemiology investigations of nosocomial outbreaks; moreover,
      knowledge of antibiotic susceptibility patterns of the prevalent pathogens in
      certain institutions may help clinicians to formulate empiric antimicrobial
      treatments for febrile granulocytopenic patients. Careful quantitative studies
      involving determinations of the minimal inhibitory concentrations may help to
      evidence early, potentially clinically significant decreases in susceptibility to
      first choice antibiotics for important nosocomial pathogens. Relationship between
      appropriate or inappropriate treatment, based on in-vitro susceptibility testing
      results, and clinical outcome may help to define the clinical significance of
      some emerging bacterial pathogens in immunocompromised patients.

PMID- 9248971
TI  - The chemotherapeutic formula revisited.

PMID- 9248972
TI  - The use of cefotaxime for the treatment of common infections: in vitro,
      pharmacokinetic and clinical considerations.
AB  - The use of the broad-spectrum cephalosporin, cefotaxime, in internal medicine is
      well-established, particularly in the treatment of moderately severe to severe
      community- and hospital-acquired infections. It is particularly useful for
      infections of the lower respiratory tract, urinary and biliary systems, skin and
      soft tissue, and in serious conditions, such as meningitis, particularly in
      pediatric patients. Knowledge of the pharmacokinetic and pharmacodynamic
      properties of cefotaxime supports the view that low dose (1-2 g), low frequency
      (12-hourly) dosage regimens are applicable to many mild-to-moderately severe
      infections, including community-acquired pneumonia, caused by susceptible
      organisms.

PMID- 9248973
TI  - Cefotaxime in the treatment of prophylaxis of surgical infections.
AB  - Cefotaxime has retained its broad-spectrum activity against the key pathogens in
      surgical infection, despite 15 years of widespread use. It has good activity
      against a wide range of Gram-positive and Gram-negative aerobes and most
      anaerobes, except Bacteroides fragilis but, combined with metronidazole, it
      offers clinically complete coverage of B. fragilis and Escherichia coli, the two
      most important species involved in intra-abdominal infections. For mixed
      infections involving B. fragilis, 500 mg metronidazole 12-hourly should be added
      to the cefotaxime regimen. Cefotaxime therapy is simple, generally inexpensive
      and has a relatively broad spectrum of activity compared to many other
      antimicrobials used for postoperative nosocomial pneumonia. Treatment with
      cefotaxime at 1 g or 2 g can be 12-hourly. Surgical prophylaxis with single-dose
      cefotaxime (1 g or 2 g) is as effective as with many other agents, with no
      documented selection of resistance. Clinical experience gained worldwide strongly
      supports the use of cefotaxime for the treatment of prophylaxis and surgical
      infections.

PMID- 9248974
TI  - Pharmacoeconomic aspects of antibacterial treatment with cefotaxime.
AB  - Pharmacoeconomics is a relatively new discipline, which is becoming increasingly
      useful in the current climate of medical advances that continue despite limited
      access to healthcare resources. Pharmacoeconomics may be used as a tool,
      assisting healthcare decision makers to select clinically beneficial therapies
      and weigh clinical gain against expenditure. Cefotaxime has been shown in many
      studies to be a cost-effective antibiotic agent, its monetary value being
      augmented by its use in low dose, low frequency regimens. This cost
      effectiveness, combined with a maintained broad spectrum of antibiotic activity,
      low propensity for selecting resistant bacterial strains and high therapeutic
      index, makes cefotaxime a suitable antibiotic agent in many indications involving
      mild-to-moderate infections by susceptible organisms.

PMID- 9248975
TI  - Empiric therapy in lower respiratory tract infection--an ongoing challenge.
AB  - Lower respiratory tract infections are a common cause of morbidity and mortality.
      The pattern of pneumonia is altering, owing to changes in a number of influencing
      factors. These include patient characteristics, such as an aging population,
      increased immunosuppression and chronic disease, and changes in medical practice.
      There is also an increasing level of resistance to antimicrobial agents by
      organisms such as Streptococcus pneumoniae and Haemophilus influenzae, the
      pathogens most commonly associated with community-acquired pneumonia. In the
      management of pneumonia, it is important to be able to differentiate between
      atypical and typical pneumonia in the clinical setting and to grade the severity
      of the infection. Currently, there are no internationally agreed treatment
      recommendations for pneumonia. The role of antimicrobial agents in acute
      exacerbations of chronic bronchitis is still a controversial issue.

PMID- 9248976
TI  - Respiratory tract infection: epidemiology and surveillance.
AB  - Streptococcus pneumoniae and Haemophilus influenzae are the key pathogens
      implicated in bacterial infections of the upper and lower respiratory tract.
      Choice of empiric oral antimicrobial chemotherapy is guided by the clinical
      presentation, severity of the infection and epidemiological knowledge. beta
      Lactams and the macrolides are the two major groups of antibiotics used to treat
      respiratory tract infections. The prevalence of penicillin-resistant strains of
      S. pneumoniae is increasing world-wide (up to 30% in the USA), as is the
      prevalence of beta-lactamase-producing strains of H. influenzae. Macrolide
      resistance in S. pneumoniae is increasing and is absolute, and some of the
      macrolides have only limited activity against H. influenzae. Knowledge of local
      and global antibiotic resistance patterns should be used as the key to directing
      empiric choice of antibiotic treatment.

PMID- 9248977
TI  - Trends in the activity of macrolide and beta-lactam antibiotics and resistance
      development. Alexander Project Group.
AB  - The Alexander Project is an ongoing international multicenter study monitoring
      trends in the antimicrobial susceptibilities of community-acquired lower
      respiratory tract (LRT) pathogens. In 1995, 4011 isolates were collected. The
      incidence of beta-lactamase-positive Haemophilus influenzae was 28.4% in the
      United States and 15.4% in Europe, and the incidence of beta-lactamase-positive
      Moraxella catarrhalis has risen to > 90% in Europe and the United States. The
      incidence of penicillin-resistant Streptococcus pneumoniae is higher in Europe
      (24.9%) than the Unites States (12.3%). For the majority of centers, there is a
      marked association between penicillin and macrolide resistance in S. pneumoniae
      with erythromycin, azithromycin and clarithromycin exhibiting MIC90s of > or = 32
      mg/l against penicillin-resistant strains. For Toulouse and Genoa, at least, the
      high levels of macrolide resistance may be attributable to high macrolide usage.
      Ceftriaxone and amoxycillin/clavulanate are the most potent agents for empirical
      therapy, with MIC90s of < or = 2 mg/l against all three principal pathogens. The
      majority of oral agents studied are active against > 90% H. influenzae and M.
      catarrhalis and > 80% S. pneumoniae on breakpoint criteria. However, on the basis
      of the time above MIC criteria for the beta-lactam and macrolide agents tested,
      only amoxycillin/clavulanate and the parenteral agent ceftriaxone can be
      recommended for empirical therapy of LRT infections caused by these pathogens.

PMID- 9248978
TI  - Strategies to minimize the development of antibiotic resistance.
AB  - The choice of appropriate antimicrobial agents should take into consideration not
      only the interests of the individual patient, but also the ecological impact of
      different drugs and their delivery schedules. Selection of antibiotic-resistant
      organisms is a key aspect to remember. Bacterial populations harboring
      determinants of antibiotic resistance will be selected for by a range of
      antibiotic concentrations which are able to suppress or slow the growth of
      susceptible populations. These concentrations (selective concentrations) will be
      achieved within the human body in a series of compartments (selective
      compartments), where the potential selective power will be roughly proportional
      to the time of exposure of the bacteria to the drug (selective period). The
      duration of the expected exposure of bacterial populations to these
      concentrations of the drugs and the number of challenges they experience are
      probably the most important factors in predicting the potential selective
      activity of an antibiotic regimen. Such a risk analysis procedure may be used to
      propose guidelines for minimizing the development of antibiotic resistance.

PMID- 9248979
TI  - Relevance of pharmacokinetics and pharmacodynamics in the selection of
      antibiotics for respiratory tract infections.
AB  - The pharmacodynamic principles that link the concentrations of antibiotics within
      body systems and their effects have been elucidated only recently. Animal work,
      now confirmed by clinical studies, has shown that for beta-lactam antibiotics,
      the time that the serum concentration exceeds the minimum inhibitory
      concentration (MIC) value of the pathogen is a key parameter in predicting a
      successful clinical and bacteriological outcome. The situation with the
      macrolides is less clear; time above MIC is the dynamic variable likely to be
      most closely linked to efficacy for erythromycin and clarithromycin but for
      azithromycin it appears to be the area under the plasma concentration-time curve:
      MIC ratio. Different antibiotics are appropriate for the key pathogens in
      community-acquired respiratory tract infections. For Streptococcus pneumoniae,
      amoxycillin/clavulanate is effective with varying dosage regimens providing
      around 40% time above the MIC90, in contrast to the oral cephalosporins and the
      macrolides for which serum concentrations do not exceed the MIC90. For
      Haemophilus influenzae, amoxycillin/clavulanate and cefixime are suitable
      antibiotics whereas macrolides have limited activity. With the exception of
      amoxycillin, all the beta-lactam and macrolide antibiotics reviewed here perform
      better against Moraxella catarrhalis than against the other two principal
      community-acquired respiratory tract pathogens and there is a wide choice of
      appropriate agents. Knowledge of the pharmacodynamically-linked variables for
      different antibiotics allows optimization of dosage regimens and direct
      comparisons across agents for the same variables.

PMID- 9248980
TI  - Overcoming language barriers when teaching the Advanced Trauma Life Support
      course.

PMID- 9248981
TI  - Detection of cytokine mRNA in unfractionated peripheral blood by reverse
      transcriptase polymerase chain reaction.
AB  - OBJECTIVE: To detect cytokine gene expression in unfractionated peripheral blood
      by reverse transcriptase-polymerase chain reaction (RT-PCR). DESIGN: Prospective
      study. SETTING: University hospital, Japan. SUBJECTS: 3 healthy volunteers and 3
      severely infected patients. INTERVENTIONS: Peripheral blood was obtained and
      total RNA was extracted from 0.5 ml unfractionated whole blood with a 4 M
      guanidinium isothiocyanate mixture, 0.2 M sodium acetate, phenol, and chloroform.
      The mRNA was reverse transcripted, and interleukin-1 beta (IL-1beta) and tumour
      necrosis factor (TNF) cDNA were selectively amplified by synthetic primers with
      PCR. MAIN OUTCOME MEASURES: Establishment of cytokine gene expression in
      unfractionated peripheral blood. RESULTS: About 10 microg of total RNA was
      obtained from a 0.5 ml sample of blood. IL-1beta and TNF mRNA were not detected
      in blood from healthy volunteers, though they were detected in patients with
      severe infection. CONCLUSION: This method avoids artefactual gene activation and
      may be applicable to monitoring cytokine gene expression in various
      pathophysiological states.

PMID- 9248982
TI  - Postoperative changes in serum interleukin-2 concentrations.
AB  - OBJECTIVE: To evaluate the postoperative changes in circulating interleukin-2 (IL
      2) concentration according to the severity of the surgical injury and other
      postoperative variables that could influence IL-2 production. DESIGN: Prospective
      observational study. SETTING: University hospital, Italy. SUBJECTS: 43 patients
      about to undergo major operations (gastric and colo-rectal resection for cancer),
      intermediate operations (open cholecystectomy or mastectomy for cancer), and
      minor operations (hernia repair or breast lump); 24 healthy age and sex matched
      controls. MAIN OUTCOME MEASURES: Postoperative changes in serum concentrations of
      IL-2 after different degrees of surgery on the 1st, 3rd and 8th postoperative
      days correlated with changes in in vivo cellular mediated immunity (skin tests),
      duration of operation, blood transfusion or postoperative H2-blockers and
      antiprostaglandins. RESULTS: There were no significant variations in IL-2 serum
      concentrations postoperatively on ANOVA, and when the data were normalised, there
      were no significant changes in the median postoperative values after minor and
      intermediate operations. There was a slight but not significant increase in IL-2
      concentrations after major operations. Neither blood transfusion nor duration of
      operation correlated with postoperative changes in IL-2, while postoperative
      antiprostaglandins and H2-blockers seemed to provide slight but not significant
      protection against a reduction in IL-2 concentrations. CONCLUSIONS: Circulating
      IL-2 does not necessarily correlate with reported in vitro postoperative
      production of IL-2 and therefore seems to be of little use in monitoring
      immunosuppression in surgical patients.

PMID- 9248983
TI  - Duration of postoperative pneumoperitoneum.
AB  - OBJECTIVE: To find out the duration of postoperative pneumoperitoneum and the
      factors that are responsible for its persistence. DESIGN: Prospective open (non
      random) study. SETTING: County hospital, Denmark. SUBJECTS: 32 patients over 18
      years of age undergoing abdominal operations during a 6 month period.
      INTERVENTIONS: Abdominal radiographs with the patient in the left lateral
      position were taken at fixed time intervals until no free air could be seen. MAIN
      OUTCOME MEASURES: The amount of free air and the time postoperatively by which it
      had disappeared. RESULTS: In 20 [corrected] patients the air had disappeared
      within 48 hours and only one patient (3%) had free air for more than five days
      postoperatively. High body mass index and a small initial amount of free air were
      associated with the shortest period of postoperative pneumoperitoneum.
      CONCLUSION: Postoperative pneumoperitoneum disappeared within two days in most
      patients. Heavier patients and patients with small volumes of free air initially
      had the shortest duration of pneumoperitoneum. There were large variations among
      patients in the volumes of free air.

PMID- 9248984
TI  - Surgical outcome and cost-minimisation-analyses of laparoscopic and open hernia
      repair: a randomised prospective trial with one year follow up.
AB  - OBJECTIVE: To compare outcome and costs between laparoscopic and open hernia
      repair. DESIGN: Prospective randomised study. SETTING: One university and two
      district hospitals in Sweden. SUBJECTS: 200 men aged 25-75 years. MAIN OUTCOME
      MEASURES: Operating time, hospital stay, complications, and time to recovery. A
      cost-minimisation-analysis was used in which the total costs were calculated for
      a defined period of time for each option. RESULT: The one year follow-up rate was
      98%. Mean (SD) operation times in the laparoscopic and open groups were 72 (30)
      and 62 (25) minutes, respectively (p = 0.009). Hospital stay and complication
      rates did not differ between the groups. Among employees the mean (SD) periods
      off work in the laparoscopic and open groups were 10 (8) and 23 (21) days,
      respectively (p = 0.0001). The mean direct costs of the laparoscopic operation
      were increased by SEK 4037 (US$ 483) but the savings in indirect costs resulting
      from earlier return to work were SEK 11392 (US$ 1364). CONCLUSIONS: Laparoscopic
      hernia repair gave the employed patients faster recovery and return to work, and
      was the most cost-effective strategy provided that both direct and indirect costs
      were included.

PMID- 9248985
TI  - The effect of preoperative high dose methylprednisolone in attenuating the
      metabolic response after oesophageal resection.
AB  - OBJECTIVE: To evaluate the effect of giving glucocorticoids preoperatively for
      the prophylaxis of surgical stress. DESIGN: Prospective randomised study.
      SETTING: University hospital, Japan. SUBJECTS: 30 patients undergoing resection
      of oesophageal carcinoma. INTERVENTIONS: 15 patients (group 1) were randomised to
      be given methylprednisolone (30 mg/kg) and 15 patients (group 2) to be given
      saline intravenously before operation. MAIN OUTCOME MEASURES: Outcome, length of
      stay in the intensive care unit (ICU), metabolic response, and oxygenation.
      RESULTS: Patients given methylprednisolone had a mean stay in the ICU of 5.1 +/-
      1.0 days compared with 8.2 +/- 4.5 days in the saline group (p < 0.01). 5
      patients in the saline group compared with 0 in the methylprednisolone group
      developed postoperative complications (p = 0.02). Plasma norepinephrine and
      arginine vasopressin levels in methylprednisolone group were significantly lower
      than those in the saline group (p < 0.05). The PaO2:FiO2 ratio in the saline
      group was significantly lower than that in the experimental group (p < 0.01).
      CONCLUSIONS: Preoperative methylprednisolone may facilitate the postoperative
      management of surgical patients.

PMID- 9248986
TI  - Acalculous cholecystitis in patients undergoing bone marrow transplantation.
AB  - OBJECTIVE: To evaluate factors associated with acalculous cholecystitis in
      patients undergoing bone marrow transplantation and the role of repeat ultrasound
      examinations. DESIGN: Retrospective study. SETTING: University hospital, United
      States. SUBJECTS: 381 Patients who underwent bone marrow transplantation between
      1987 and 1992. INTERVENTIONS: Abdominal ultrasound examination (n = 134), repeat
      ultrasound in those considered to have acalculous cholecystitis (n = 8), and
      acute cholecystectomy (n = 5). RESULTS: 14 Patients (4%) with acalculous
      cholecystitis were identified. The 8 who had had liver tissue examined also had
      veno-occlusive disease of the liver. It was possible to follow progressing or
      resolving acalculous cholecystitis by repeat ultrasound examinations. 4 Of the 5
      patients treated surgically survived, compared with 3 of the 9 not operated on.
      CONCLUSIONS: Acalculous cholecystitis was associated with veno-occlusive disease
      of the liver. Repeat ultrasound examinations were valuable in showing progressing
      or resolving acalculous cholecystitis and may guide treatment. Cholecystectomy
      seems to be a safe procedure for acalculous cholecystitis in patients undergoing
      bone marrow transplantation.

PMID- 9248987
TI  - Vertical banded gastroplasty or gastric banding for morbid obesity: effects on
      gastro-oesophageal reflux.
AB  - OBJECTIVE: To assess the effect of vertical banded gastroplasty and gastric
      banding on the development of gastro-oesophageal reflux using both subjective and
      objective methods. DESIGN: Prospective, randomised study. SETTING: Teaching
      hospital, Sweden. SUBJECTS: 50 consecutive, morbidly obese patients (mean (SD)
      body mass index (BMI) 42.5 (5), 27 women and 23 men; mean age 48 years, range 38
      57 years). INTERVENTIONS: Vertical banded gastroplasty (n = 24) or gastric
      banding (n = 26). MAIN OUTCOME MEASURES: Results of evaluation by standardised
      questionnaire, 24-hour ambulatory pH-metry, and endoscopy. RESULTS: After six
      months the mean (SD) BMI had decreased to 34.4 (5.7), with no differences between
      the groups. Mild dysphagia was somewhat more common (13 compared with 1) but the
      incidence of heartburn (8 compared with 17), and acid regurgitation (12 compared
      with 14) were less after the operation; 3 patients developed erosive
      oesophagitis, two in the vertical banded group and one in the banding group.
      Ambulatory pH-metry readings did not change significantly from preoperatively and
      there were no differences between the two operations. One patient developed
      pathological reflux, and in three the values returned to the normal range.
      CONCLUSION: Gastric restriction operations including those with a narrow stoma
      that causes outflow obstruction do not seem to increase the incidence of reflux
      in patients with functioning antireflux barriers.

PMID- 9248989
TI  - Likely gains in life expectancy of patients with coronary artery disease treated
      with HMG-CoA reductase inhibitors, as predicted by a decision analysis model.
AB  - OBJECTIVE: To estimate the likely gains in life expectancy of patients with
      coronary artery disease treated with HMG-CoA reductase inhibitors based on
      published reports and the results of the 4S and the West of Scotland Study.
      DESIGN: Decision analysis. MAIN OUTCOME: Four likely scenarios of the effect of
      treatment with HMG-CoA reductase inhibitors on the life expectancy of medically
      and surgically managed coronary artery disease were modelled. RESULTS: Regardless
      of the scenario, treatment with HMG-CoA reductase inhibitors was estimated to
      provide a gain in life expectancy for medically managed patients of all ages with
      coronary artery disease, ranging from 4.6 to 10.1 quality adjusted life years
      (QALYs) for a 40 year old with three vessel disease (depending on the scenario
      assumed), to 0.2 QALYs for a 80 year old with two vessel disease. These gains
      were always greater than those predicted after bypass alone. If the use of HMG
      CoA reductase inhibitors produces the same reduction in cardiac mortality after
      bypass as it does in medically managed patients it will increase the benefits of
      operation except for patients with two vessel disease over 70 years of age.
      Conversely, if HMG-CoA reductase inhibitors do not influence the course of
      coronary artery disease after bypass, the benefits of operation over medical
      treatment with HMG-CoA reductase inhibitors are either reduced or lost
      completely, ranging from a loss of -5.6 QALYs for a 40 year old with two vessel
      disease to a gain of 1.5 QALYs for 55 to 60 year old patients with left main stem
      disease. CONCLUSION: Although their effect on the progression of coronary artery
      disease after bypass must be defined, it is probable that HMG-CoA reductase
      inhibitors will produce considerable gains in life expectancy for patients with
      coronary artery disease.

PMID- 9248990
TI  - Fixed rectal cancer at laparatomy: a simple operation to protect the small bowel
      from radiation enteritis.

PMID- 9248988
TI  - Additional value of biochemical tests in suspected acute appendicitis.
AB  - OBJECTIVE: To evaluate the efficacy of biochemical tests in diagnosing acute
      appendicitis. DESIGN: Open prospective study. SETTING: District hospital, Norway.
      SUBJECTS: 257 patients with suspected acute appendicitis. INTERVENTIONS: Initial
      diagnostic accuracy of a logistic regression model using available clinical data
      was compared with results of corresponding models that included an increasing
      number of inflammatory parameters. MAIN OUTCOME MEASURES: The estimated
      probabilities of appendicitis in different testing groups were analysed using
      receiver operating characteristic (ROC) curves. RESULTS: A model including only
      clinical variables had a mean area under the ROC curve of 0.854. When the total
      white blood cell count, C-reactive protein concentration, and neutrophil count
      were added, the model improved significantly to 0.920. CONCLUSION: Biochemical
      tests are of additional value in a computer model, and the tests should, if used
      rationally, also provide physicians with important information in the
      investigation of acute appendicitis.

PMID- 9248991
TI  - Intra-abdominal ectopic thyroid presenting as a pancreatic tumour.

PMID- 9248992
TI  - Pyomyositis--a differential diagnosis in the acute abdomen.

PMID- 9248993
TI  - Mitochondrial fusion promoting plasmid.

PMID- 9248994
TI  - Chondrocyte migration to fibronectin, type I collagen, and type II collagen.
AB  - It is well known that cellular interactions, such as cell adhesion, migration,
      invasion, between cells and the extracellular matrix are mediated by the integrin
      family of cell surface receptors. Chondrocytes are surrounded by an abundant
      extracellular matrix, but there is less information on the cellular receptors
      which interact with this matrix. In our studies, fibronectin, type I collagen,
      and type II collagen promoted haptotactic and chemotactic migration of
      chondrocytes, as determined using a modified Boyden chamber system. Treatment of
      chondrocytes with tyrosine kinase inhibitor, herbimycin or genistein, resulted in
      a dose dependent inhibition of migration toward these matrix proteins, whereas
      adhesion of chondrocytes was not influenced. This indicated the existence of
      functional relationships between protein tyrosine phosphorylation and chondrocyte
      migration following the adhesion of chondrocytes to matrix proteins. Further
      study showed that the peptide GRGDSP inhibited chondrocyte migration to
      fibronectin but not to collagens. On the other hand, chondrocytes migrated toward
      the tetra-RGD containing peptide, but not the peptide GRGDSP, in a dose dependent
      fashion. These observations suggest that cross-linking or clustering of integrins
      is essential to induce transmembrane signaling related to tyrosine
      phosphorylation for chondrocyte migration toward fibronectin.

PMID- 9248995
TI  - Relationship between the host cell endoplasmic reticulum and the parasitophorous
      vacuole containing Toxoplasma gondii.
AB  - Tachyzoites of Toxoplasma gondii multiplies within the parasitophorous vacuole
      (PV) of the host cell. Simultaneously with parasite division growth of the
      vacuole takes place. Using immunofluorescence microscopy and antibodies
      recognizing calreticulin, a nonmuscle functional analogue of calsequestrin, and a
      76 kDa glycoprotein localized in the endoplasmic reticulum (ER), we showed the
      incorporation of ER elements of the host cell into parasitophorous vacuole
      containing-T. gondii. In addition enzyme cytochemistry showed that glucose-6
      phosphatase, an enzyme marker of ER, is also localized within the PV. These
      observations suggest that growth of T. gondii -- containing PV is at least in
      part due to incorporation of elements of the host cell ER into the vacuole.

PMID- 9248996
TI  - Process of dispersion and fragmentation of Golgi complex by microtubule bundles
      formed in taxol treated HeLa cells.
AB  - By means of a monoclonal antibody (mAbG3A5) against Golgi membrane glycoprotein,
      we have visualized the relative position of cytoplasmic polymerized microtubule
      bundles to Golgi stack cisternae in taxol treated HeLa cells, and found extensive
      fragmentation of the Golgi stack cisternae brought about by microtubule bundles.
      Within a 1 h period of taxol treatment, polymerization of cytoplasmic
      microtubules increased rapidly to form microtubule bundles, while the Golgi
      complex dispersed slightly along with the polymerized microtubule bundles. After
      2 to 3 h taxol treatment the dispersal of the Golgi complex from the microtubule
      organizing center (MTOC) to cytoplasmic periphery rapidly progressed in the
      direction which the microtubules ran. At early dispersal, the microtubule bundles
      were oriented apart from the stretched end of the Golgi stack cisternae and
      exhibited little direct contact with the Golgi stack cisternae membrane. The
      Golgi stack cisternae then began to wind around the microtubule bundles, followed
      by the beginning of fragmentation of the Golgi stack cisternae. At this step,
      some of the microtubules seemed to attach to a part of the Golgi stack cisternae.
      After prolonged exposure of cells to taxol (25 h) the microtubule bundles were
      highly developed throughout the cells and most of the Golgi fragments were
      trapped at their termini. In these cells, extensive fragmentation of Golgi stack
      cisternae occurred, resulting in small Golgi vesicles bound to the microtubule
      bundle.

PMID- 9248997
TI  - A green fluorescent protein-actin fusion protein dominantly inhibits cytokinesis,
      cell spreading, and locomotion in Dictyostelium.
AB  - We transformed Dictyostelium discoideum cells by a vector for expression of a
      chimerical fusion protein consisting of Aequorea Victoria green fluorescent
      protein (GFP) and D. discoideum actin at its amino- and carboxy-terminal,
      respectively. The amount of expressed GFP-actin was about 3% of total actin
      molecules in the transformed cells. The expression of GFP-actin in D. discoideum
      completely inhibited cytokinesis in suspension culture. The expression decreased
      the rate of random cell locomotion to about a half of that of control cells. The
      expression also caused the cells to round up. These phenotypic observations
      suggested that GFP-actin acts as a dominant negative form of actin in the cells.
      The rounding up by expression of GFP-actin was suppressed by genetical
      elimination of myosin II heavy chain. This result suggested that myosin II is
      necessary for the rounding up of GFP-actin expressing cells. GFP-actin
      constructed cortical actin filament architectures together with intrinsic actin
      in the cells. Purified GFP-actin polymerized and de-polymerized repetitively
      according to the solution conditions in vitro. The critical concentration of GFP
      actin for polymerization is the same as that of actin. The GFP-actin filaments
      was able to bind to coverglass surfaces coated with myosin head fragments.
      However, the GFP-actin filaments did not slide at all on the coverglass by
      addition of ATP. This indicates that the GFP-actin filaments form rigor complex
      with myosin II in vitro even in the presence of ATP. The formation of rigor
      complex may cause the cells to round up.

PMID- 9248998
TI  - Effects of melatonin on proliferation, oxidative stress and Cx32 gap junction
      protein expression in primary cultures of adult rat hepatocytes.
AB  - Melatonin has antiproliferative and antioxidant effects on cells in vivo and in
      vitro. Gap junctions mediate the communication between adjacent cells and are
      closely related to cellular growth and oxidative stress. We previously reported
      that 2% dimethylsulfoxide (DMSO) which has antiproliferative and antioxidative
      effects on hepatocytes, induces connexin 32 (Cx32) gap junction protein in
      primary cultures of adult rat hepatocytes. In the present study, we have examined
      the effects of melatonin on proliferation, oxidant stress and Cx32 gap junction
      protein expression in the cultured rat hepatocytes as compared to 2% DMSO
      treatment. 10(-2) M melatonin significantly inhibited the proliferation and the
      oxidative stress of the cells, and markedly induced Cx32 gap junction protein
      expression and gap junctional intercellular communication (GJIC). These effects
      of 10(-2) M melatonin treatment were not due to cytotoxicity to the cultured rat
      hepatocytes and they were as strong as those of 2% DMSO treatment. These results
      suggested that melatonin might be a useful substance to maintain the functions of
      the hepatocytes in vitro by modulating the levels of proliferation, oxidative
      stress and gap junction expression.

PMID- 9248999
TI  - Selective stimulation of granulopoiesis in vitro by established bone marrow
      stromal cells.
AB  - Bone marrow is a major granulopoietic organ whose hematopoietic microenvironment
      is comprised of stromal cells. In the present work, we examined the regulation of
      in vitro granulopoiesis with an established line of bone marrow stromal cells. In
      coculture of the progenitor cells on the particular stromal cell lines from bone
      marrow, large granulocyte (G) colonies consisting of over 200 cells were formed
      without G-CSF for 5 days. Stromal cells supported development of Gr-1
      (granulocyte specific surface marker)-negative progenitors into Gr-1 and
      myeloperoxidase positive granulocytes. Seventy percent of the large G-colonies
      were formed on the stromal layers even in the presence of anti-G-CSF antibody,
      which indicates the G-CSF independent pathway of granulopoiesis. Inhibition of
      the large G-colony formation by the addition of anti-adhesion molecules, such as
      very late activation antigen-4 (VLA-4) and CD31 (PECAM-1), suggested the role of
      cell-to-cell adhesion in stroma-supported granulopoiesis.

PMID- 9249000
TI  - Immunocytochemical analysis of peptide hormone processing: importance of the
      positively charged N-terminal domain of signal peptide in correct ER targeting in
      yeast cells.
AB  - We used a morphological approach to determine the topogenic role of the signal
      peptide in mediating the ER translocation of yeast prepro-alpha-factor. In prepro
      alpha-factor-somatostatin hybrids, changes in the N-terminal amino acid sequence
      from wild-type NH2-Met-Arg-Phe (MRF) to NH2-Met-Phe-Lys (MFK) caused a subtle
      difference in protein trafficking in yeast cells. Immunofluorescence microscopy
      on semithin cryosections and immunoelectron microscopy on ultrathin sections
      showed that the transposition of the charged amino acid at N-terminus caused the
      precursors to be associated with either nucleus or mitochondria. This suggests
      that the secretory proteins are mistargeted to the irrelevant organelles as the
      result of inefficient ER translocation. Structural aspects of nuclear or
      mitochondrial targeting proteins and common principles in membrane translocation
      systems account for the mistargeting of overexpressed mutant hybrid precursors
      that are not rapidly translocated into the ER. Based on our immunocytochemical
      study on individual cells, we propose here that the positively charged N-terminal
      domain of signal peptide is important not merely in the efficiency of ER
      translocation, but also in appropriate targeting of peptide hormone precursors in
      yeast cells where post-translational ER translocation is known to occur
      frequently.

PMID- 9249001
TI  - Evidence for muscarinic 3 receptor mediated ion transport in HT29 cells studied
      by X-ray microanalysis.
AB  - Changes in elemental content in response to muscarinic drugs in HT29 cells were
      investigated by X-ray microanalysis. Acetylcholine (ACh) and carbachol (Cch),
      both agonists binding to muscarinic receptors, induced a decrease of the
      intracellular Cl and K content. This agrees with the notion that these agonists
      induce electrolyte and water secretion. Atropine, a non-selective antagonist of
      muscarinic receptors, inhibited the decrease in K and Cl caused by ACh and Cch,
      and instead caused an increase of the Cl and K concentrations. A similar
      inhibition was found in the case of the selective muscarinic 3 receptor
      antagonist P-F-HHSiD. In contrast, the selective muscarinic 2 receptor antagonist
      AF-DX 116 did not inhibit Cch-activated secretion of K and Cl. A slight
      inhibition of ACh induced ion secretion was seen, but this inhibition was weak
      compared to that caused by P-F-HHSiD. Treatment with U-73122, an inhibitor of
      phospholipase C, blocked ACh or Cch induced ion secretion. These results suggest
      that ACh and Cch stimulated secretion of Cl and K is mediated by muscarinic 3
      receptors via the inositol-1,4,5-trisphosphate (IP3) dependent pathway.

PMID- 9249002
TI  - A decade of protein engineering on ribonuclease T1--atomic dissection of the
      enzyme-substrate interactions.
AB  - During the last decade, protein engineering has been used to identify the
      residues that contribute to the ribonuclease-T1-catalyzed transesterification.
      His40, Glu58 and His92 accelerate the associative nucleophilic displacement at
      the phosphate atom by the entering 2'-oxygen downstream guanosines in a highly
      cooperative manner. Glu58, assisted by the protonated His40 imidazole, abstracts
      a proton from the 2'-oxygen, while His92 protonates the leaving group. Tyr38,
      Arg77 and Phe100 further stabilize the transition state of the reaction. A
      functionally independent subsite, including Asn36 and Asn98, contributes to
      chemical turnover by aligning the substrate relative to the catalytic side chains
      upon binding of the leaving group. An invariant structural motive, involving
      residues 42-46, renders ribonuclease T1 guanine specific through a series of
      intermolar hydrogen bonds. Tyr42 contributes significantly to guanine binding
      through a parallel face-to-face stacking interaction. Tyr45, often referred to as
      the lid of the guanine-binding site, does not contribute to the binding of the
      base.

PMID- 9249004
TI  - Neutral glycosphingolipids induce cell-cell aggregation of a variety of
      hematopoietic cell lines.
AB  - Exogenous neutral glycosphingolipids induced homotypic cell-cell aggregation of a
      variety of hematopoietic cell lines. A mouse cytotoxic T cell line, CTLL-2, was
      chosen to study the neutral glycosphingolipid-induced aggregation. Among neutral
      glycosphingolipids tested, galactosylceramide (GalCer) and glucosylceramide
      (GlcCer) were potent inducers, followed by lactosylceramide (LacCer);
      globotriaosylceramide (Gb3Cer) and neolactotetraosylceramide (nLc4Cer) were less
      effective. GalCer that contained a non-hydroxy fatty acid was more efficient than
      GalCer containing an alpha-hydroxy fatty acid. The minimum concentration of
      GalCer containing a non-hydroxy fatty acid that induced aggregation was 1 microM,
      and maximum aggregation occurred at 10-20 microM within 24 h. Cytochalasin B and
      a mixture of sodium azide and 2-deoxyglucose inhibited the aggregation, whereas
      cycloheximide, actinomycin D, and colchicine did not. Aggregated and dispersed
      cells, which were designated as competent cells, re-aggregated in the absence of
      neutral glycosphingolipids. Anti-GalCer polyclonal antibody inhibited GalCer
      induced reaggregation. Furthermore, competent cells bound and aggregated non
      competent cells in the absence of neutral glycosphingolipids. Cell-cell
      aggregatign was similar for CTLL-2 cells and the other hematopoietic cells that
      were tested. These findings suggest that the neutral glycosphingolipid-induced
      cell-cell aggregation of CTLL-2 cells was mediated by heterophilic interaction(s)
      between glycosphingolipids and other cell surface components. These properties
      are shared by a variety of hematopoietic cell lines.

PMID- 9249003
TI  - Cleavage requirements for activation of factor V by factor Xa.
AB  - Coagulation factor V circulates in plasma as a single chain protein which
      expresses little procoagulant activity. After its activation by limited
      proteolysis by thrombin or factor Xa, factor Va functions as cofactor to factor
      Xa in the activation of prothrombin. Thrombin cleaves human factor V at Arg709,
      Arg1018 and Arg1545 and factor Va is formed by the heavy and light chains, which
      correspond to the N-terminal and C-terminal fragments, respectively. Factor Xa
      has been shown to cleave factor V at Arg1018 and at a second undefined position
      close to Arg709. The factor-Xa-mediated cleavage at Arg1018 has been proposed to
      be sufficient for expression of full factor Va activity. To study the activation
      of factor V by factor Xa, site-directed mutagenesis was used to convert Arg709 to
      Gln, Arg1018 to Ile, and Arg1545 to Gln. Constructs containing all possible
      combinations of native and mutated residues in these positions were expressed
      transiently in COS 1 cells. The various factor-V mutants were incubated with
      factor Xa or thrombin. The proteolytic cleavage pattern was analyzed by Western
      blotting, and the specific factor-Va activities determined in a prothrombinase
      assay. Control experiments using thrombin gave results which were in agreement
      with those on record, i.e. cleavages at both Arg709 and Arg1545 were required for
      expression of full factor-Va activity, whereas the cleavage at Arg1018 enhanced
      the rate of cleavage at Arg1545. Factor Xa was found to cleave factor V at all
      three thrombin cleavage sites, i.e. at Arg709, Arg1018 and Arg1545. An additional
      factor-Xa-cleavage site was found in the light chain region at Arg1765. Cleavage
      at Arg1018 by factor Xa was not sufficient for expression of full factor-Va
      activity. Full factor-Va activity was only obtained after cleavage at both Arg709
      and Arg1545. The factor-Xa-mediated cleavage at Arg709 was kinetically favourable
      over that at Arg1545. Factor V which was mutated at all three sites (at positions
      709, 1018 and 1545) was resistant to activation by thrombin. However, treatment
      with factor Xa yielded an increased factor-Va activity which was associated with
      the cleavage at Arg1765. Our study extends previously results on thrombin
      activation of factor V and elucidates the relative importance of the different
      cleavage sites for activation of factor V by factor Xa.

PMID- 9249005
TI  - Quantitative analyses of myosin heavy-chain mRNA and protein isoforms in single
      fibers reveal a pronounced fiber heterogeneity in normal rabbit muscles.
AB  - A highly sensitive method of reverse-transcriptase polymerase chain reaction (RT
      PCR) was established to study myosin heavy-chain (MHC) mRNA isoform expression in
      single fibers of rabbit limb muscles. In combination with myofibrillar adenosine
      triphosphatase histochemistry and electrophoretic separation of MHC protein
      isoforms in fragments of the same fibers, the direct RT-PCR method identified the
      pMHC20-40 and pMHC24-79 cDNA sequences as being specific to MHCIIb and MHCIId/x
      isoforms, respectively. In addition, a direct RT-PCR was established for
      determining relative amounts of MHC mRNA isoforms by using a sequence specific to
      alpha-skeletal actin as an endogenous reference. Analyses of large amounts of
      single fibers revealed an unexpected heterogeneity of the fast fiber population
      with regard to numerous fibers coexpressing MHCIIb and MHCIId/x. Based on
      quantitative RT-PCR, the percentages of MHCIIb/MHCIId hybrid fibers amounted to
      approximately 55% in the deep portion of gastrocnemius, to 43% in the adductor
      magnus, and to 12% in psoas muscle. Moreover, the two MHC mRNA isoforms were
      nonuniformly distributed along the fiber length. Qualitative RT-PCR detected even
      higher amounts of hybrid fibers in the three muscles. The percentages of hybrid
      fibers identified at the protein level were smaller in adductor magnus muscle
      (25%) and psoas muscle (5%), but equaled that of the mRNA analysis in
      gastrocnemius muscle (61%). The detection of high amounts of IIBD and IIDB fibers
      suggested that hybrid fibers represent functional elements within the fiber
      spectrum of normal muscles. Our observations on hybrid fibers reveal a
      heterogeneity within the fiber population of normal muscles that has not been
      realized to date.

PMID- 9249006
TI  - Selective fast degradation of cytochrome P-450 2E1 in serum-deprived hepatoma
      cells by a mechanism sensitive to inhibitors of vesicular transport.
AB  - Cytochrome P-450 2E1 (CYP2E1) is characterized by a rapid turnover in the liver
      and some cell lines and the ability of substrates and heme iron ligands to
      inhibit significantly enzyme degradation. In the Fao hepatoma cell line, CYP2E1
      was found to be fairly stable (half-life of 26 h), but serum withdrawal resulted
      in its rapid disappearance from the microsomal fraction (half-life of about 7 h)
      as evaluated using cycloheximide chase. The effect of serum withdrawal could be
      partially reversed by the addition of albumin to the culture medium, whereas
      insulin and the insulin-like growth factor IGF-I had no additional effect. The
      effect of serum withdrawal was specific for CYP2E1 since (a) no concomitant fast
      degradation of CYP2B1 and NADPH-cytochrome P-450 reductase was observed and (b)
      the CYP2E1 ligands ethanol and imidazole prevented the fast degradation of the
      enzyme. The lysosomotropic agent ammonium chloride and the inhibitor of
      autophagocytosis 3-methyladenine slowed down CYP2E1 degradation by about 30%,
      while leupeptin had no effect. Under the same conditions, the degradation of
      total long-lived cell protein showed the same sensitivity to ammonium chloride,
      but was significantly less sensitive to 3-methyladenine and serum and not
      sensitive to ethanol and imidazole. CYP2E1 degradation was inhibited by combined
      treatment with brefeldin A and nocodazole, which blocks both anterograde and
      retrograde vesicular transport between endoplasmic reticulum and the Golgi
      apparatus. The data point to the existence of a selective mechanism for the
      degradation of membrane proteins in serum-deprived cells in addition to
      nonselective autophagocytosis. The selective degradation of CYP2E1 may be
      attained by means of its selective vesicular transport to an acidic post
      endoplasmic reticulum compartment.

PMID- 9249007
TI  - The role of CCAAT/enhancer-binding protein alpha and a protein that binds to the
      activator-protein-1 site in the regulation of liver-specific expression of the
      winter flounder antifreeze protein gene.
AB  - Winter flounder, Pleuronectes americanus, produces antifreeze proteins (AFPs) to
      avoid freezing during winter. The AFP in the blood is synthesized by the liver
      and its annual level is regulated by environmental factors and somatotropin. The
      only intron (+106 to +602) of the AFP gene contains putative binding sites for
      liver-enriched transcription activators. Due to the lack of an appropriate fish
      liver cell line, a mammalian model system was used to demonstrate the liver
      specific enhancer activity of the intron. Deletion analysis of the intron
      indicated nucleotide sequences between +192 bp and +334 bp were important for the
      enhancer activity. Further refinement showed that the element B (+303 to +322 bp)
      resided in this region interacted with proteins from rat nuclear extracts by
      DNase I footprinting and mobility shift analysis. Gel retardation with
      competition and supershift experiments defined element B to include binding sites
      for CCAAT/enhancer binding protein a (C/EBP alpha), a liver-enriched
      transcription factor, and a novel activator protein-1 (AP-1) site binding
      protein, designated as antifreeze enhancer binding protein (AEP). Residues
      important to DNA-protein interaction in element B were mapped by methylation
      interference. Mutations in element B by site-directed mutagenesis destroyed the
      enhancer activity of the intron. Ultraviolet crosslinking experiments using
      element B revealed the specific binding of two proteins of approximately 43 and
      80 kDa. The present findings provide a mechanism(s) by which the tissue
      specificity of AFP gene expression can be achieved. Integration of the present
      information with the somatotropin-mediated signal transduction pathways has
      generated a working model for the hormonal regulation and seasonal expression of
      the AFP gene.

PMID- 9249008
TI  - Purification and characterization of a mitochondrial, single-stranded-DNA-binding
      protein from Paracentrotus lividus eggs.
AB  - A binding protein for single-stranded DNA was purified from Paracentrotus lividus
      egg mitochondria to near homogeneity by chromatography on DEAE-Sephacel and
      single-stranded-DNA-cellulose. The protein consists of a single polypeptide of
      about 15 kDa. Glycerol gradient sedimentation analysis suggested that P. lividus
      mitochondrial single-stranded-DNA-binding protein exists as a homo-oligomer,
      possibly a tetramer, in solution. The protein shows a stronger preference for
      poly(dT) with respect to single-stranded M13, poly(dI) and poly(dC). Binding to
      poly(dA) takes place with much lower affinity. The binding-site size, determined
      by gel mobility-shift experiments with oligonucleotides of different length, is
      approximately 45 nucleotides. The binding to single-stranded DNA occurs with low
      or no cooperativity and is not influenced by ionic strength. The protein has a
      very high affinity for the DNA: its apparent macroscopic association constant is
      2x10(9) M(-1), a value which is the highest among the mitochondrial single
      stranded-DNA-binding proteins characterized to date. The lack of cooperativity
      and the high association constant represent distinctive features of this protein
      and might be related to the peculiar mechanism of sea urchin mitochondrial DNA
      replication.

PMID- 9249009
TI  - Interaction of N-tosyl-L-phenylalanylchloromethane with Thermus thermophilus
      elongation factor Tu.
AB  - The interaction of N-tosyl-L-phenylalanylchloromethane (TosPheCH2Cl) with Thermus
      thermophilus elongation factor Tu (EF-Tu) was studied by affinity labelling and
      NMR spectroscopy. TosPheCH2Cl binds to GDP and GTP conformers of EF-Tu. The
      interaction of TosPheCH2Cl with EF-Tu x GDP leads to alkylation of Cys82, while
      interaction of TosPheCH2Cl with EF-Tu x GTP does not lead to covalent labelling.
      [A82]EF-Tu, in which the Cys82 is replaced by Ala, has similar properties to wild
      type EF-Tu with respect to GTPase activity, binding of guanine nucleotides,
      interaction with elongation factor Ts (EF-Ts) and interaction with ribosomes.
      This structural change did not lead to changes, compared with wild-type EF-Tu in
      the functionality of [A82]EF-Tu, either in the GTP or in the GDP conformation.
      TosPheCH2Cl binds to EF-Tu x GTP with a dissociation constant of 10 microM. The
      interaction of TosPheCH2Cl with EF-Tu promotes the hydration of the carbonyl
      group of TosPheCH2Cl. TosPheCH2Cl competes with aminoacyl-tRNA for its binding
      site on EF-Tu x GTP. Covalent modification of Cys82 by TosPheCH2Cl does not
      prevent nucleotide binding and GTPase activity, but interferes with the
      interaction with aminoacyl-tRNA. TosPheCH2Cl probably mimics the aminoacyl
      residue of the aminoacyl-tRNA and binds to its binding site on EF-Tu x GTP. This
      rather specific interaction with EF-Tu x GTP does not allow the modification of
      Cys82, whereas the loose interaction of TosPheCH2Cl with EF-Tu x GDP leads to
      alkylation of this residue.

PMID- 9249010
TI  - Design and solution structure of a partially rigid opioid antagonist lacking the
      basic center--models of antagonism.
AB  - To discriminate between two general models of antagonism (participation and
      allosteric), an opioid antagonist lacking the basic nitrogen of tyramine was
      designed and characterized. Cyclo-[Tyr(Me)2-Tic-], the diketopiperazine of 2,6
      dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, is a partially
      rigid opioid antagonist; its pA2 (5.8) is one smaller than that of N,N-bisallyl
      enkephalin but it has a very high binding affinity (10 nM) and has a delta
      selectivity (66 with respect to the binding to mu receptors) higher than that of
      naltrindole. The conformational state of this diketopiperazine, studied under a
      variety of solvent and temperature conditions by NMR and molecular dynamics, can
      be described in terms of only three conformers whose relative populations vary
      widely with solvent. Only one of the three conformers, characterized by a 90
      degree arrangement of the aromatic rings of Tyr(Me)2 and Tic similar to those of
      rigid agonists and of the bioactive conformation of the corresponding linear
      antagonist, is consistent with the antagonist activity. This finding favors the
      participation model among the general mechanisms proposed to explain antagonism.
      Due to the simple composition of the conformational mixture and to the rigidity
      of the molecule, it is possible to propose a quantitative explanation for the
      discrepancy between the very high binding affinity (10 nM) and the fairly small
      in mouse vas deferens value (1.5 microM).

PMID- 9249011
TI  - The replacement of Lys620 by serine desensitizes Escherichia coli
      phosphoenolpyruvate carboxylase to the effects of the feedback inhibitors L
      aspartate and L-malate.
AB  - Chemical modification of Escherichia coli phosphoenolpyruvate carboxylase (P
      pyruvate carboxylase) by 2,4,6-trinitrobenzene sulfonate, a specific reagent for
      amino groups, causes desensitization to allosteric inhibitors, L-aspartate and L
      malate, as well as inactivation. When L-malate is included in the modification
      mixture, P-pyruvate carboxylase was markedly protected from both desensitization
      and inactivation [Naide, A., Izui, K., Yoshinaga, T. & Katsuki, H. (1979) J.
      Biochem. (Tokyo) 85, 423-432]. To determine the lysine residue(s) involved in
      allosteric inhibition, the lysine residues that were protected from modification
      by L-malate were investigated by analyzing trinitrophenylated peptides liberated
      by digestion with glutamyl endopeptidase (V8-protease). The identified residues
      were Lys491, Lys620, Lys650, and Lys773. Each of these residues was individually
      replaced with an alanine or serine residue by site-directed mutagenesis to
      produce mutant enzymes. The mutant enzyme whose lysine residue was replaced with
      serine ([Ser620]P-pyruvate carboxylase) showed a marked desensitization to L
      aspartate and L-malate, while retaining almost the same maximal catalytic
      activity as the wild-type P-pyruvate carboxylase. Essentially no changes in
      enzymatic properties were observed for the [Ala491]- and [Ala650]P-pyruvate
      carboxylases, while for the [Ala620]- and [Ala773]P-pyruvate carboxylases the
      polypeptides of the expected size were not significantly accumulated in the
      transformed E. coli cells, presumably due to intracellular degradation.

PMID- 9249012
TI  - Structural investigation of the lipopolysaccharide from Acinetobacter
      haemolyticus strain NCTC 10305 (ATCC 17906, DNA group 4).
AB  - The structure of the lipopolysaccharide (LPS) from Acinetobacter haemolyticus
      strain NCTC 10305 (DNA group 4) was elucidated by means of analytical chemistry,
      NMR spectroscopy and fast-atom-bombardment mass spectrometry. Several
      oligosaccharides were obtained after deacylation or successive de-O-acylation,
      dephosphorylation, reduction, and de-N-acylation of LPS. In the major fraction of
      the LPS, the core is attached to the lipid A through D-glycero-D-talo-2
      octulopyranosonic acid (Ko), whereas in a minor fraction (<20%) Ko is replaced by
      3-deoxy-D-manno-octulopyranosonic acid (Kdo). The structures of the
      phosphorylated carbohydrate backbones of these LPS fractions are [structure: see
      text] with Dha = 3-deoxy-D-lyxo-2-heptulosaric acid, Sug = sugar and is Ko in a
      major fraction and Kdo in a minor fraction. All sugar residues have the D
      configuration and are present in the pyranose form. Mass spectrometry of de-O
      acylated LPS revealed the presence of an additional hexose residue in minor
      amounts, the position and nature of which could not be identified.

PMID- 9249013
TI  - Up-regulation of the ubiquitin-conjugating and proteolytic systems in murine
      acquired immunodeficiency syndrome.
AB  - Lymphoproliferation, chronic B-cell activation resulting in
      hypergammaglobulinemia, and profound immunodeficiency are prominent features of
      retrovirus-induced murine acquired immunodeficiency syndrome (murine AIDS). Here
      we demonstrate that in murine AIDS the ATP-dependent and ubiquitin-dependent
      proteolytic system is strongly affected, at least in the lymph nodes of infected
      mice. Solid-phase immunochemical assays show that the ubiquitin-conjugate pools
      increase by about threefold 10 weeks after infection, then decline slightly 15
      weeks after infection to a twofold increase. Accumulation of ubiquitin conjugates
      is accompanied by induction of the ubiquitin-conjugating pathway, involving
      several carrier-protein isozymes (E2), mainly 14-kDa E2 and 17-kDa E2.
      Furthermore, accumulation of ubiquitin conjugates and induction of the
      conjugating system are coincident with an increase in the proteolytic activity
      supported by the 26S proteolytic complex. However, 15 weeks after infection, when
      the conjugation rate and levels of ubiquitin conjugates decrease, proteasome
      activity returns to values similar to those of the control, suggesting that a
      higher proteosomal activity is no longer needed. The concerted induction of the
      ubiquitin-conjugating and proteolytic systems in murine AIDS apparently does not
      involve the breakdown of viral products nor is it supported by virus-coded
      events, but probably arises as a cellular response to viral infection.

PMID- 9249014
TI  - Quantification of MyoD, myogenin, MRF4 and Id-1 by reverse-transcriptase
      polymerase chain reaction in rat muscles--effects of hypothyroidism and chronic
      low-frequency stimulation.
AB  - A highly sensitive method of reverse-transcriptase polymerase chain reaction (RT
      PCR) was established to quantify transcript levels of the myogenic regulatory
      factors MyoD, myogenin and MRF4 (muscle regulatory factor 4) and for Id-1
      (inhibitor of differentiation), a putative negative regulator of myogenesis. The
      method was sensitive enough to detect mRNA amounts as low as 20 molecules.
      Measurements in 10 different skeletal muscles of the rat revealed that the
      amounts of the four factors differ by almost three orders of magnitude. Id-1 is
      expressed at lowest levels (approximately 4x10(5) molecules/microg RNA) and MRF4
      at highest levels (approximately 9x10(7) molecules/microg RNA). In general,
      myogenin and MyoD mRNAs were inversely distributed in slow and fast muscles. A
      correlation seemed to exist between the levels of MyoD and myosin heavy chain
      (MHC) IIb, the fastest MHC isoform. However, as revealed by changes in the
      expression levels of these two regulatory factors under conditions of
      hypothyroidism and chronic low-frequency stimulation (CLFS), MyoD and myogenin
      did not seem to be strictly correlated with fast and slow myosins, respectively.
      Hypothyroidism led to pronounced depressions of MyoD, but only to small increases
      in myogenin mRNA in fast muscles. These changes were only slightly increased by
      CLFS. However, as previously shown, CLFS in combination with hypothyroidism
      induces in rat muscle pronounced fast to slow transitions in myosin expression
      [Kirschbaum, B. J., Kucher. H.-B., Termin, A., Kelly, A. M. & Pette, D. (1990) J.
      Biol. Chem. 265, 13974-13980]. These findings suggest that MyoD and myogenin may
      not be causally related to the development and maintenance of fiber-type
      diversities.

PMID- 9249015
TI  - cDNA cloning and expression of secreted Xenopus laevis dipeptidyl aminopeptidase
      IV.
AB  - From a Xenopus laevis skin library a cDNA coding for dipeptidyl aminopeptidase IV
      (DPP IV) was isolated. The ORF codes for a protein with sequence similarity to
      DPP-IV-like proteins, including mammalian DPP IV and X. laevis fibroblast
      activation factor. In contrast to the membrane-bound mammalian enzymes, mature X.
      laevis DPP IV is a soluble secreted polypeptide. The frog enzyme possesses a
      cleavable signal sequence; the mature protein starts at Thr30 of the polypeptide
      predicted from the cDNA sequence. Expression of the cloned cDNA by recombinant
      vaccinia virus resulted in the formation of a protein with the expected molecular
      mass and substrate specificity. Recombinant DPP IV was present in high
      concentration in the supernatant of infected cells and exhibited enzymatic
      activity towards the synthetic substrate alanyl-prolyl-p-nitroanilide.

PMID- 9249016
TI  - Influence of charge differences in the C-terminal part of nisin on antimicrobial
      activity and signaling capacity.
AB  - Three mutants of the antibiotic nisin Z, in which the Val32 residue was replaced
      by a Glu, Lys or Trp residue, were produced and characterized for the purpose of
      establishing the role of charge differences in the C-terminal part of nisin on
      antimicrobial activity and signaling properties. 1H-NMR analyses showed that all
      three mutants harbor an unmodified serine residue at position 33, instead of the
      usual dehydroalanine. Apparently, the nature of the residue preceding the serine
      to be dehydrated, strongly affects the efficiency of modification. Cleavage of
      [Glu32,Ser33]nisin Z by endoproteinase Glu-C yielded [Glu32]nisin Z(1-32)
      peptide, which has a net charge difference of -2 relative to wild-type nisin Z.
      The activity of [Lys32,Ser33]nisin Z against Micrococcus flavus was similar to
      that of wild-type nisin, while [Trp32,Ser33]nisin Z, [Glu32,Ser33]nisin Z and
      [Glu32]nisin Z(1-32)-peptide exhibited 3-5-fold reduced activity, indicating that
      negative charges in the C-terminal part of nisin Z are detrimental for activity.
      All variants showed significant loss of activity against Streptococcus
      thermophilus. The potency of the nisin variants to act as signaling molecules for
      auto-induction of biosynthesis was significantly reduced. To obtain mutant
      production, extracellular addition of (mutant) nisin Z to the lactococcal
      expression strains was essential.

PMID- 9249017
TI  - Cerastotin, a serine protease from Cerastes cerastes venom, with platelet
      aggregating and agglutinating properties.
AB  - Cerastotin, a thrombin-like enzyme from the venom of the desert viper Cerastes
      cerastes, has been purified by gel filtration on Sephadex G-75 and two ion
      exchange chromatographies on Mono S columns. It is a neutral glycoprotein (pI =
      6.6), present as a single polypeptide chain of 40 kDa. Its N-terminal sequence
      shows strong similarity with those of other thrombin-like enzymes from snake
      venoms. Cerastotin possesses esterase and amidolytic activities measured with
      N(alpha)-tosyl-L-arginine methyl ester and the thrombin chromogenic substrate D
      phenylalanyl-L-pipecolyl-L-arginine p-nitroanilide, respectively. The amidolytic
      activity is inhibited by phenylmethylsulfonyl fluoride, N(alpha)-tosyl-L-lysine
      chloromethane, N(alpha)-tosyl-L-phenylalanyl chloromethane, D-phenylalanyl-L
      prolyl-L-arginyl chloromethane and benzamidine, suggesting that cerastotin is a
      serine protease. Cerastotin efficiently clots human plasma and cleaves
      preferentially the alpha chain of fibrinogen. Cerastotin did not induce
      aggregation of washed normal platelets, but did aggregate platelets in the
      presence of exogenous fibrinogen. A monoclonal antibody directed against
      glycoprotein (GPIb), which specifically inhibits induced agglutination by
      ristocetin also completely blocks platelet aggregation induced by cerastotin.
      However, another anti-GPIb monoclonal antibody, which specifically inhibits alpha
      thrombin binding to GPIb, did not prevent this aggregation. Furthermore,
      platelets which were desensitised by alpha-thrombin still aggregate in the
      presence of cerastotin, but not alpha-thrombin. Similarly a monoclonal antibody,
      anti-GPIIb-IIIa, which blocks fibrinogen binding, did not inhibit cerastotin
      induced platelet aggregation. This activity is abolished in the presence of 1 mM
      phenylmethylsulfonyl fluoride and/or 10 mM EDTA. Cerastotin also agglutinates
      formalin-fixed and washed platelets, only in the simultaneous presence of
      fibrinogen and of Von Willebrand factor.

PMID- 9249018
TI  - 7alpha-Hydroxylation and 3-dehydrogenation abolish the ability of 25
      hydroxycholesterol and 27-hydroxycholesterol to induce apoptosis in thymocytes.
AB  - Oxygenated derivatives of sterols (oxysterols), including 25-hydroxycholesterol
      and 27-hydroxycholesterol, have immunosuppressive effects. Oxysterols can
      directly induce apoptosis in immature thymocytes, cells which are inherently
      sensitive to induction of programmed cell death. For that reason, the metabolism
      of 25-hydroxycholesterol and 27-hydroxycholesterol in mouse thymus has been
      studied. When incubated with thymic tissue, both oxysterols were found to be
      7alpha-hydroxylated with subsequent oxidation to 7alpha-hydroxy-3-oxo-delta4
      steroids. A minor fraction of 27-hydroxycholesterol was also metabolised to 3beta
      hydroxy-5-cholestenoic, 3beta,7alpha-dihydroxy-5-cholestenoic and 7alpha-hydroxy
      3-oxo-4-cholestenoic acids. The 7alpha-hydroxylase was found to be localised to
      the thymic epithelial cells and the reaction was stimulated by interleukin-1beta
      and inhibited by metyrapone and RU486. In contrast to 25-hydroxycholesterol and
      27-hydroxycholesterol, the 7alpha-hydroxylated metabolites, 7alpha,25
      dihydroxycholesterol, 7alpha,25-dihydroxy-4-cholesten-3-one and 7alpha,27
      dihydroxy-4-cholesten-3-one did not induce thymocyte apoptosis. The results
      suggest that 7alpha-hydroxylation may be of regulatory importance, possibly by
      protecting the developing thymocytes against toxic effects by oxysterols.

PMID- 9249019
TI  - High-molecular-mass complexes of human minichromosome-maintenance proteins in
      mitotic cells.
AB  - Minichromosome-maintenance (Mcm) proteins perform essential functions regulating
      the replication of eukaryotic genomes. In interphase cells they are either bound
      to a nuclear structure, most probably chromatin, or occur as free multiprotein
      complexes in the nucleoplasm. Mcm proteins are displaced from their chromatin
      sites during S phase, and several become highly phosphorylated during mitosis. We
      investigated whether phosphorylation affects the ability of mitotic Mcm proteins
      to form multiprotein complexes. Our results clearly show that phosphorylated
      mitotic Mcm proteins form a 14-15-S complex, probably consisting of one molecule
      each of the six known human Mcm proteins.

PMID- 9249020
TI  - Periplasmic Bar1 protease of Saccharomyces cerevisiae is active before reaching
      its extracellular destination.
AB  - Saccharomyces cerevisiae MATa and MAT alpha cells secrete a-factor and alpha
      factor pheromones. These peptides act on cells of the opposite mating type. They
      induce physiological changes which allow the formation of diploid cells. MATa
      strains produce an extracellular protease which cleaves, and thus inactivates the
      MAT alpha cell-specific alpha-factor pheromone. This pepsin-like enzyme is
      encoded by the BAR1(SST1) gene and is secreted into the periplasmic space of MATa
      cells. We found that the Bar1p protease is already active in early compartments
      of the secretory pathway. Our results indicate that Bar1 protease tolerates large
      N-terminal extensions of its substrate and does not require Golgi-specific
      modifications such as outer-chain glycosylation for activity.

PMID- 9249021
TI  - Structural and functional analysis of the promoter of the hepatic lipase gene.
AB  - Hepatic lipase (HL) gene transcription is almost exclusively limited to
      hepatocytes. Here we have studied sequences and transcription factors regulating
      basal and hepatocyte-restricted HL promoter activity. Sequencing of a cloned 3.4
      kb HL promoter fragment revealed three Alu repeat sequences and a consensus
      hepatocyte-enriched nuclear transcription factor 1 (HNF1) binding site located
      upstream of one major and one minor transcription initiation site. By
      transfection of cell lines of hepatic and non-hepatic origin and of primary
      hepatocyte cultures, sequences controlling basic HL promoter activity and
      negative elements located downstream and upstream thereof which extinguish or
      enhance this activity were defined. Some HL-promoter fragments with internal
      deletions were active only in primary hepatocyte cultures. Human HNF1 protein was
      shown to bind to the HL-specific HNF1 response element and the activity of a
      heterologous promoter was enhanced by HL-HNF1 in rat primary hepatocyte cultures
      but not in the context of the authentic 3.4-kb HL promoter sequences. In cell
      lines the presence of HNF4 but not of HNF1 and vHNF1 mRNA was found to correlate
      with HL gene expression although no perfect consensus HNF4 binding motif was
      detected in the promoter region tested. Taken together, these data indicate that
      hepatocyte-specific HL gene transcription is controlled by positive and negative
      transcription regulatory proteins which bind to sequence motifs within and
      outside of the proximal 3.4-kb promoter fragment studied. For the elucidation of
      the control of HL promoter activity in vivo the use of primary hepatocyte
      cultures is essential.

PMID- 9249022
TI  - Mapping of nuclease-sensitive sites in native reticulocyte ribosomes--an analysis
      of the accessibility of ribosomal RNA to enzymatic cleavage.
AB  - Treatment of ribosomes in reticulocyte lysates with low concentrations of the
      calcium-dependent nuclease from Staphylococcus aureus resulted in cleavage of
      rRNA. The positions of the cleaved phosphodiester bonds were localised by primer
      extension and polyacrylamide gel electrophoresis. S. aureus nuclease-induced
      strand scissions were found in the 5'-domain of 18S rRNA and in domains II, IV
      and VI of 28S rRNA. The majority of the cleavage sites were located in eukaryote
      specific expansion segments and only one cleavage site was found in a region
      suggested to be directly involved in ribosomal function. Treatment of the
      reticulocyte lysate with increasing amounts of S. aureus nuclease resulted in the
      introduction of new cleavage sites. However, even at the highest nuclease
      concentration used, large parts of the rRNAs were protected from nuclease
      digestion. Removal of translational components, by salt wash of isolated
      reticulocyte polysomes, exposed additional rRNA sequences to S. aureus nuclease
      cleavage. These sequences were found in the 3'-major domain of 18S rRNA and in
      domains II, IV, and V of 28S rRNA. These sites are located at the putative
      translational surface of the ribosome. The translational activity of the S.
      aureus nuclease-treated ribosomes, determined after addition of exogenous mRNA,
      was directly correlated to the extent of nuclease digestion of the ribosomes.
      However, the decrease in translational activity observed in lysates treated with
      low amounts of S. aureus nuclease was not due to a preferential exclusion of
      damaged ribosomes from polysome formation. This suggests that the induced
      cleavages were not detrimental to ribosomal function but could influence the rate
      of ribosomal movement along the mRNA.

PMID- 9249023
TI  - Enhanced stability of urokinase-type plasminogen activator mRNA in metastatic
      breast cancer MDA-MB-231 cells and LLC-PK1 cells down-regulated for protein
      kinase C--correlation with cytoplasmic heterogeneous nuclear ribonucleoprotein C.
AB  - In LLC-PK1 cells, urokinase-type plasminogen activator (uPA) mRNA has a short
      half-life of 70 min. We have previously demonstrated that most of the regulatory
      regions responsible for the rapid turnover of uPA mRNA in LLC-PK1 cells reside in
      its 3' untranslated region (3' UTR), where there are at least three regulatory
      sites, one of which is A+U-rich. This A+U-rich sequence mediates uPA mRNA
      stabilization induced by protein kinase C (PKC) down-regulation. In this work, we
      found that uPA mRNA is rather stable in MDA-MB-231 cells with a half-life of 17
      h. We compared the stability of hybrid globin mRNA containing different parts of
      uPA mRNA in its 3' UTR and found that the A+U-rich sequence of uPA mRNA renders
      otherwise stable globin mRNA unstable in LLC-PK1 cells but not in MDA-MB-231
      cells. We identified a cytoplasmic protein of 40 kDa (p40) which specifically
      interacts with the A+U-rich sequence. Levels of p40 activity as detected by
      ultraviolet cross-linking were higher in MDA-MB-231 and PKC-down-regulated LLC
      PK1 cells than in untreated LLC-PK1 cells. Prior treatment of the cytoplasm with
      a specific antibody against heterogeneous nuclear ribonucleoprotein C (hnRNP C)
      significantly reduced p40 activity. These results suggest a correlation between
      the A+U-rich sequence-dependent uPA mRNA stabilization in vivo and the binding of
      hnRNP C to the A+U-rich sequence in vitro.

PMID- 9249024
TI  - Evidence for the existence of multiple heparan sulfate proteoglycans in the human
      glomerular basement membrane and mesangial matrix.
AB  - Heparan sulfate proteoglycans (HSPGs) are essential components of the glomerular
      basement membrane (GBM) carrying a strong anionic charge. A well-characterized
      extracellular HSPG is perlecan, ubiquitously expressed in basement membranes. A
      cDNA construct encoding domains I and II of human perlecan was expressed as a
      fusion protein with glutathione S-transferase. This fusion protein was used to
      generate monoclonal antibody 95J10. We compared the staining pattern of 95J10
      with that of M215, a previously prepared mAb that recognizes HSPG isolated from
      human GBM. In kidney cortex, the anti-perlecan mAb 95J10 showed a strong staining
      of the mesangium, Bowman's capsule, the tubular basement membrane, and stained
      the GBM only slightly. In contrast, M215 predominantly stained the GBM in a
      linear fashion. Immunoelectron microscopy supported these results, showing
      concentrations of perlecan in some regions of the GBM, whereas the unidentified
      M215 antigen was homogenously distributed throughout the GBM. In other human
      tissues, both antibodies also produced a different staining pattern. Furthermore,
      a polyclonal antiserum recognizing HSPG isolated from the GBM did not recognize
      perlecan from EHS tumors. These results provide evidence for the presence of
      another HSPG in the GBM that is immunologically distinct from perlecan. The
      absence of perlecan splice variants in the kidney suggests that this component is
      encoded by a different gene than perlecan. Given its marked expression in the
      GBM, this component could be a determining factor in the maintenance of selective
      glomerular permeability.

PMID- 9249025
TI  - A 54-kDa protein specifically associates the 3' untranslated region of three
      maternal mRNAs with the cytoskeleton of the animal part of the Paracertrotus
      lividus egg.
AB  - Bep mRNAs, i.e., maternal messengers coding for cell surface proteins, are
      localized in the animal part of Paracertrotus lividus egg and embryos. Here we
      have examined the involvement of the cytoskeleton in asymmetric distribution of
      bep3 mRNA. Moreover, in order to understand whether and how cis- and trans-acting
      factors are necessary for bep3 mRNA localization, we have looked for in vitro
      specific interactions between egg proteins and bep3 mRNA. By northwestern assay
      we have identified a 54-kDa protein that binds to the 3'UTR of bep3 mRNA. This 54
      kDa protein also permits association of 3'UTR of bep3 with cytoskeleton elements,
      indicating its involvement in the localization process. Binding of 54-kDa protein
      to 3'UTR of bep1 and bep4 has also been demonstrated, suggesting that a binding
      motif is shared with these other two mRNAs of the same gene family. Northwestern
      analyses carried out utilizing proteins extracted from different developmental
      stages indicate that the 54-kDa protein is the only protein able to bind to the
      3'UTR of bep3.

PMID- 9249026
TI  - Genetic and biochemical characterization of the broad spectrum chlorobenzene
      dioxygenase from Burkholderia sp. strain PS12--dechlorination of 1,2,4,5
      tetrachlorobenzene.
AB  - The bacterium, Burkholderia (previously Pseudomonas) sp. strain PS12, reported
      earlier to degrade 1,2,4-trichlorobenzene is shown here to utilize also 1,2,4,5
      tetrachlorobenzene (Cl4-benzene) as a growth substrate. To investigate the
      possibility that this organism attacks Cl4-benzene with a chlorobenzene
      dioxygenase which concomitantly causes dehalogenation, and to analyze the
      substrate range of the initial enzyme, a 5503-bp DNA fragment from PS12,
      exhibiting high similarity to genes coding for class IIB dioxygenases, was cloned
      and expressed in Escherichia coli. The sequence includes the tec genes coding for
      the alpha-subunit and beta-subunit of a terminal dioxygenase, a ferredoxin and a
      reductase. E. coli cells producing these proteins were able to dioxygenolytically
      attack a range of aromatic compounds including chlorinated benzenes and toluene,
      and also dinuclear aromatics such as biphenyl and dibenzo-p-dioxin. The enzyme
      was shown by (18)O2 incorporation experiments to dioxygenolytically attack a
      chlorosubstituted carbon atom of Cl4-benzene, thereby forming an unstable diol
      intermediate which spontaneously rearomatizes with concomitant chloride
      elimination to the corresponding 3,4,6-trichlorocatechol (Cl3-catechol).

PMID- 9249027
TI  - Tissue-specific expression of promoter regions of the alpha1(VI) collagen gene in
      cell cultures and transgenic mice.
AB  - Cis-acting regions regulating transcription of the alpha1(VI) collagen chain have
      been investigated in vitro by transfection of promoter-CAT (where CAT is
      chloramphenicol acetyltransferase) constructs in different types of cultured
      cells and in vivo in transgenic mice carrying the same CAT constructs or
      minigenes derived from the fusion of genomic and cDNA sequences in which small
      deletions of the collagenous domain had been engineered. 215 bp of 5'-flanking
      sequence showed promoter activity in vitro, yet were not expressed in any tissue
      of six transgenic lines, indicating that this fragment contains the basal
      promoter, but not activator sequences. Constructs with 0.6 and 1.4 kb of the 5'
      flanking region produced significantly higher CAT activity in transfected cells
      and were expressed in tissues of about 30% of transgenic lines. Although CAT
      activity was totally unrelated to the pattern of expression of the alpha1(VI)
      mRNA, these results suggest the presence of an activator(s) between -0.2 and -0.6
      kb from the transcription start site. When the promoter size was increased to 5.4
      or 6.5 kb, CAT activity was stimulated severalfold relative to the construct
      p1.4CAT and p4.0CAT in NIH3T3 fibroblasts and chick embryo chondroblasts. This
      stimulation was, however, not observed in C2C12 myoblasts. Transgenic mice
      generated with 6.5CAT construct or minigenes, containing 6.2 kb of promoter,
      exhibited very high levels of expression, which was similar to the relative
      amount alpha1(VI) mRNA in the majority of tissues, with the exception of lung,
      adrenal gland and uterus. CAT activity in tissues was 100-1000-fold higher than
      that measured in transgenic mice with shorter promoter (0.6 or 1.4 kb). Since
      expression of minigenes was determined by RNase protection assay, the levels of
      mRNA per transgene copy were compared to those of the chromosomal gene and found
      to be always less than one quarter. These data suggest that the region -4.0/-5.4
      contains an important activator(s) sequence which induces transcription in
      several, but not all, type VI collagen-producing tissues. Finally, analysis with
      the longest promoter fragment (7.5 kb) revealed a complex effect of the region 
      6.5/-7.5 on alpha1(VI) chain transcription. The sequence was inhibitory in NIH3T3
      cells, indifferent in myoblasts and activating in chondroblasts in vitro, whereas
      transgenic animals generated with 7.5CAT construct produced a pattern of
      expression comparable to that of 6.5CAT and minigenes. During postnatal
      development transcription from both the endogenous gene and the transgenes
      decreased. However, the ratio of transgene/chromosomal gene expression was not
      constant, but varied in a way dependent on the tissue. This observation suggests
      that the fragment studied contains key sequences for the age-dependent regulation
      of the alpha1(VI) gene. No phenotypic alterations were induced by the presence of
      mutations in the minigenes.

PMID- 9249028
TI  - Mode of primary binding to target membranes and pore formation induced by Vibrio
      cholerae cytolysin (hemolysin).
AB  - Vibrio cholerae cytolysin (VCC) is produced by many non-choleratoxigenic strains
      of V. cholerae, and possibly represents a relevant pathogenicity determinant of
      these bacteria. The protein is secreted as a pro-toxin that is proteolytically
      cleaved to yield the active toxin with a molecular mass of approximately 63 kDa.
      We here describe a simple procedure for preparative isolation of mature VCC from
      bacterial culture supernatants, and present information on its mode of binding
      and pore formation in biological membranes. At low concentrations, toxin monomers
      interact with a high-affinity binding site on highly susceptible rabbit
      erythrocytes. This as yet unidentified binding site is absent on human
      erythrocytes, which are less susceptible to the toxin action. At higher
      concentrations, binding of the toxin occurs to both rabbit and human erythrocytes
      in a non-saturable manner. Cell-bound toxin monomers oligomerize to form
      supramolecular structures that are seen in the electron microscope as apparently
      hollow funnels, and oligomerization correlates functionally with the appearance
      of small transmembrane pores. Osmotic protection experiments indicate that the
      toxin channels are of finite size with a diameter of 1-2 nm. The mode of action
      of VCC closely resembles that of classical pore-forming toxins such as
      staphylococcal alpha-toxin and the aerolysin of Aeromonas hydrophila.

PMID- 9249029
TI  - Investigation of different recombinant isoforms of grass group-V allergens
      (timothy grass pollen) isolated by low-stringency cDNA hybridization--antibody
      binding capacity and allergenic activity.
AB  - A cDNA library of timothy grass pollen was screened for homologous isoforms of
      major group-V allergens by low stringency hybridization with a Phl p 5 (Phleum
      pratense) probe. After restriction analysis of the 40 clones obtained, 17 were
      selected for cDNA sequencing. Of these clones, two were unrelated to group-V
      allergens, six showed high similarity but an incomplete open reading frame and
      nine had high similarity with a complete open reading frame. Comparison of
      deduced amino acids of ten complete cDNA clones confirmed the presence of two
      major isoforms, a and b. Within these two subgroups, only minor sequence
      variations were observed. Eight isoforms were expressed in Escherichia coli K12
      and purified to homogeneity. Although the subgroups a and b could be
      distinguished by their molecular masses and by binding constants towards
      monoclonal antibodies, all isoforms turned out to be biochemically similar.
      Ribonuclease activity as a marker for the biological function of group-V
      allergens was shown to be in the same range for both subgroups. Analysis of
      allergenic B-cell responses towards the isoforms in 26 grass pollen allergic
      patients revealed that the IgE reactivities to the different isoforms were
      identical for each individual. IgE reactivities and allergenic activities of
      three isovariants and an allergen of a different group were compared in a
      selected group of four grass pollen allergic patients by immunoblot, histamine
      release and skin-prick tests. The IgE reactivity does not necessarily mirror the
      allergenic activity of the single molecule, and the variability of allergenic
      activity between the isovariants does not, in every case, depend on the
      structural differences of these allergens. We conclude that group-V isoallergens
      in grass pollen, although they can be structurally different, induce a similar B
      cell response but can show variable allergenic activity. Thus, the most
      allergenic isoform of each important group of allergens should be sufficient for
      the diagnosis of type-I allergy. Whether the isoallergenic variation has any
      significant influence on the outcome of immunotherapy in allergic disease still
      has to be elucidated.

PMID- 9249030
TI  - Acid-induced disassembly of glutamate dehydrogenase from the hyperthermophilic
      archaeon Pyrococcus furiosus occurs below pH 2.0.
AB  - The stability of the hexameric glutamate dehydrogenase from the hyperthermophilic
      archaeon Pyrococcus furiosus at low pH values has been studied by activity assay,
      spectroscopic methods, size-exclusion chromatography and ultracentrifugation
      analysis. The enzyme is exceptionally stable and at pH 2.0 its hexameric assembly
      is preserved despite the changes observed in its tertiary structure. Below pH 1.7
      dissociation into monomers starts and is accompanied by a progressive loss of
      tertiary interactions. Dissociation intermediate(s) were not detectable. At pH
      2.0 the addition of NaCl causes the same structural changes observed upon further
      addition of protons. The monomeric state of the enzyme at pH 1.0 shows a
      significant content of native secondary structure and can be unfolded by
      guanidinium chloride. The role of electrostatic interactions in the high
      stability of the enzyme structure at low pH values is discussed.

PMID- 9249031
TI  - Enzymatic semisynthesis of dicarba analogs of calcitonin.
AB  - The semisynthesis of eel[L-alpha-aminosuberic acid]calcitonin (elcatonin) was
      accomplished by alpha-chymotrypsin-catalyzed coupling of two peptide segments in
      a single reaction without the protection of any functional group. The eel
      calcitonin-(10-32)-peptide was prepared by a gene manipulation. The esters of
      cyclic desamino nonapeptide (segment 1-9) were synthesized by the conventional
      solution method including a thermolysin-mediated resolution of DL-alpha
      aminosuberic acid via one-step tripeptide synthesis leading to the 7-9 sequence.
      The main aim of this work was to determine the conditions for protease-catalyzed
      segment condensation while avoiding a concurrent cleavage of other
      proteolytically labile peptide bonds in the hormone. The alpha-chymotrypsin
      condensation strategy under usual conditions led to a complicated mixture of
      split products with an insignificant amount of the required peptide. When the
      coupling reaction was carried out at 0 degrees C, the reaction resulted in a
      satisfactory yield of elcatonin with the complete conversion of the acyl donor (1
      9 segment) accompanied by negligible concurrent peptide bond digestion. The same
      strategy was employed for the preparation of analogous dicarba salmon calcitonin
      using a synthetic elcatonin-(10-32)-peptide. Both calcitonin analogs exhibited
      hypocalcemic activity corresponding to the international standard of elcatonin.
      We demonstrate in this work a peptide synthesis based on the combination of
      genetic engineering, chemical synthesis and proteinase-catalyzed segment
      condensation. This approach enables effective incorporation of an unnatural amino
      acid into calcitonins without the side-chain protection.

PMID- 9249032
TI  - The fidelity of 3' misinsertion and mispair extension during DNA synthesis
      exhibited by two drug-resistant mutants of the reverse transcriptase of human
      immunodeficiency virus type 1 with Leu74-->Val and Glu89-->Gly.
AB  - The relatively low fidelity of DNA synthesis characteristic to the reverse
      transcriptases (RTs) of the AIDS-causing viruses, human immunodeficiency viruses
      types 1 and 2 (HIV-1 and HIV-2, respectively) was implicated as a dominant factor
      that contributes to the genetic hypervariability of these viruses. The formation
      of 3'-mispaired DNA and the subsequent extension of this DNA were shown to be key
      determinants that lead to the error proneness of these RTs. As part of our goal
      to study the structure/function relationship in HIV-1 RT, we have conducted
      mutational studies aimed at identifying amino-acid residues involved in affecting
      the fidelity of DNA synthesis by the enzyme. We have recently found that two
      mutants of HIV-1 RT, which show resistance to nucleoside analog inhibitors
      ([Leu184]RT and [Phe183]RT), exhibit in vitro error proneness of DNA synthesis
      lower than that of wild-type enzyme [Bakhanshvili, M., Avidan, O. & Hizi, A.
      (1996) Mutational studies of human immunodeficiency virus type 1 reverse
      transcriptase: the involvement of residues 183 and 184 in the fidelity of DNA
      synthesis, FEBS Lett. 391, 257-262]. Using both criteria, the current comparative
      study suggests that these two mutant RTs display a substantially enhanced
      fidelity of DNA synthesis relative to the wild-type RT counterpart. In the
      current study we have analyzed two additional drug-resistant mutants of HIV-1 RT,
      [Val74]RT and [Gly89]RT, for their in vitro fidelity of DNA synthesis using two
      parameters of DNA synthesis: 3' mispair formation and elongation of 3'-mismatched
      DNA. The current comparative study suggests that these two mutant RTs display a
      substantially enhanced fidelity of DNA synthesis relative to the wild-type RT
      counterpart, using both criteria. Analysis of the relative frequencies of
      misinsertion and mispair extension indicates that the overall error proneness of
      DNA synthesis in HIV-1 RT is wild-type > [Val74]RT > [Gly89]RT mutant. The
      results further support the possible linkage between the capacity of an enzyme to
      incorporate a nucleoside analog instead of the correct dNTP (leading to drug
      sensitivity) and the ability to incorporate and extend a wrong nucleotide
      (resulting in mutagenesis). Our results may bear on the potential use of
      selecting and maintaining HIV virions with high fidelity and drug-resistant RTs
      to suppress the subsequent appearance of virions resistant to other drugs.

PMID- 9249033
TI  - A new kinetic model for the mode of action of soluble and membrane-immobilized
      glutathione peroxidase from bovine erythrocytes--effects of selenium.
AB  - Kinetic studies on the oxidative reaction of glutathione by hydrogen peroxide
      were performed using soluble and membrane-bound ox erythrocyte glutathione
      peroxidase of various types. The effects of organic and inorganic selenium on the
      glutathione peroxidase activity were also examined. The kinetic behaviour of the
      enzyme was investigated using a coupled reaction within a relatively large range
      of hydrogen peroxide and glutathione concentrations. Non-parallel double
      reciprocal plots were obtained which suggested that a sequential ordered rather
      than a ping-pong mechanism was involved. Similar results were obtained with
      soluble and membrane-bound enzyme, whatever the type of crosslinking used.
      Crosslinking was performed on a nylon support using various alkylating agents and
      bifunctional molecules. With all three types of immobilized enzyme thus obtained,
      a slight but significant increase in the Km was observed. The effects of selenium
      were then studied. Using soluble enzyme, a slight increase in the activity was
      observed in the presence of inorganic selenium (sodium selenite) but not with
      organic selenium (seleno-L-methionine). Inorganic selenium alone was also found
      to have a slight effect on the membrane-bound enzyme. An increase in the
      catalytic efficiency was observed when glutathione peroxidase was bound using
      lysine as the bifunctional agent and either glutaraldehyde or triethyloxonium
      tetrafluoroborate as the reticulation agent, after a three-month period of
      incubation.

PMID- 9249034
TI  - Plasminogen activation by pro-urokinase in complex with its receptor--dependence
      on a tripeptide (Spectrozyme plasmin).
AB  - The intrinsic activity of single-chain pro-urinary-type plasminogen activator
      (pro-uPA) and whether its receptor (uPAR) potentiates this activity remains
      controversial. In this report, the pro-uPA/uPAR-(1-281)-peptide complex in
      solution is shown to have equivalent plasminogen-activator activity to that of
      active two-chain uPA (tc-uPA). However, the activity of the complex was dependent
      on a synthetic tripeptide, Spectrozyme plasmin (Spl, H-D-2-aminohexanoic
      acid(Ahx)-hexatyrosyl-lysine-p-nitroanilide), which can also be used as a
      chromogenic substrate for plasmin. Furthermore, this activity could be completely
      suppressed by commonly used carrier proteins and detergents. The pro-uPA/uPAR-(1
      281)-peptide complex at 1 nM displayed similar activity to that of tc-uPA for
      either [Glu1]plasminogen or [Lys77]plasminogen in chromogenic assays with Spl
      present as the plasmin substrate. When assayed with another plasmin substrate,
      S2251, the pro-uPA/uPAR-(1-281)-peptide complex was unable to activate
      plasminogen. The pro-uPA/uPAR-(1-281)-peptide complex and tc-uPA also showed a
      similar extent of plasminogen activation as measured by SDS/PAGE, when incubated
      with plasminogen and Spl in the presence of 100 micro M aprotinin, and
      plasminogen activation by pro-uPA alone was also stimulated in the presence of
      Spl in this assay. Activation of plasminogen by the pro-uPA/uPAR-(1-281)-peptide
      strictly required the presence of Spl, and pro-uPA remained in single-chain form
      during these assays. This activity of the pro-uPA/uPAR-(1-281)-peptide complex
      but not that of tc-uPA was completely inhibited by human serum albumin, bovine
      serum albumin, Tween-80, Triton X-100, and Pluronic-F68. Taken together, the data
      indicates that uPAR-(1-281)-peptide itself is not sufficient to augment pro-uPA
      activity and the presence of an effector molecule (e.g. Spl) is required to
      elicit the full plasminogen-activator activity of the pro-uPA/uPAR-(1-281)
      peptide complex. It remains to be seen whether there is a physiological
      counterpart to this phenomenon.

PMID- 9249035
TI  - Purification and properties of a cellobiose phosphorylase (CepA) and a
      cellodextrin phosphorylase (CepB) from the cellulolytic thermophile Clostridium
      stercorarium.
AB  - Two phosphorolytic enzymes displaying activity towards the soluble cellulose
      degradation products cellobiose and cellodextrins were purified from the crude
      extract of the cellulolytic thermophile Clostridium stercorarium. Both
      phosphorylases have monomeric structures with molecular masses of 93 and 91 kDa,
      respectively. Although the N-terminal amino acid sequences are highly similar, a
      clear distinction of the two enzymes could be made on the basis of their
      substrate specificities: the enzyme designated cellobiose phosphorylase cleaved
      exclusively the disaccharide substrate, whereas the enzyme designated
      cellodextrin phosphorylase accepted only oligosaccharides as substrates. Kinetic
      constants were determined for the cleavage of cellobiose and cellodextrins.
      Maximal activity was observed at 65 degrees C in the pH range 6.0-7.0 for both
      enzymes. The sequences of the genes cepA and cepB encoding the cellobiose
      phosphorylase and the cellodextrin phosphorylase, respectively, have been
      submitted to the GenBank database.

PMID- 9249036
TI  - Heterologous expression and biochemical characterization of two functionally
      different type I fatty acid synthases from Brevibacterium ammoniagenes.
AB  - The coryneform bacterium, Brevibacterium ammoniagenes, contains two structurally
      related but functionally differentiated type I fatty acid synthases, FAS-A and
      FAS-B. Isolation of homogeneous preparations of both enzymes was achieved by
      constructing specific fasA and fasB expression systems. In B. ammoniagenes,
      insertional mutagenesis of fasB allowed the specific production of enzymatically
      active FAS-A. The corresponding fasA mutant was not suited for FAS-B purification
      as the level of this enzyme was extremely low, in the fasA-disruptants. Instead,
      FAS-B could be efficiently expressed in the heterologous host, Escherichia coli.
      Using specific antisera against each of the two FAS variants, FAS-A was shown to
      be the predominant FAS protein in B. ammoniagenes. In contrast the two enzymes
      are expressed at comparable rates in E. coli even though the same upstream
      sequences were associated with fasA and fasB, as in B. ammoniagenes. Due to their
      differential capacities of being activated to the phosphopantetheine-containing
      holo-enzyme in the heterologous host, only FAS-B but not FAS-A exhibited overall
      FAS activity when isolated from E. coli. Irrespective of their origin, the
      purified FAS-A and FAS-B proteins were indistinguishable with respect to their
      flavin fluorescence, their subunit size and their sucrose density gradient
      sedimentation characteristics. Nevertheless, the in vitro products of both
      enzymes differ characteristically: while FAS-A synthesizes mainly the 18-carbon
      fatty acids oleate and stearate with only traces of palmitate, the major product
      of FAS-B is palmitic acid. No unsaturated fatty acids are produced by FAS-B.
      Thus, the two B ammoniogenes type I fatty acid synthases differ, in spite of
      their very similar overall protein structure, in both their ability to synthesize
      oleic acid and in their chain-length specificities.

PMID- 9249037
TI  - Modulation of the catalytic activity of brain succinic semialdehyde reductase by
      reaction with pyridoxal 5'-phosphate.
AB  - An NADPH-dependent succinic semialdehyde reductase from bovine brain was
      inactivated by pyridoxal 5'-phosphate. Spectral evidence is presented to indicate
      that the inactivation proceeds through formation of a Schiff's base with amino
      groups of the enzyme. After sodium borohydride reduction of the inactivated
      enzyme, it was observed that 1 mol phosphopyridoxyl residue was incorporated/mol
      enzyme monomer. The coenzyme, NADPH, protected the enzyme against inactivation by
      pyridoxal 5'-phosphate. After tryptic digestion of the enzyme modified with
      pyridoxal 5'-phosphate in the presence and absence of NADPH followed by [1H]NaBH4
      reduction, a radioactive peptide absorbing at 310 nm was isolated by reverse
      phase HPLC. The amino acid sequence of the peptide identified a portion of the
      pyridoxal-5'-phosphate-binding site as the region containing the sequence I-L-E-N
      I-Q-V-F-X-K, where X indicates that the phenylthiohydantoin amino acid could not
      be assigned. The missing residue, however, can be designated as a
      phosphopyridoxyl lysine as interpreted from the result of amino acid composition
      of the peptide. It is suggested that the catalytic function of succinic
      semialdehyde reductase is modulated by binding of pyridoxal 5'-phosphate to a
      specific lysyl residue at or near the coenzyme-binding site of the protein.

PMID- 9249038
TI  - Tetrazolium-dye-linked alcohol dehydrogenase of the methylotrophic actinomycete
      Amycolatopsis methanolica is a three-component complex.
AB  - Tetrazolium-dye-linked alcohol dehydrogenase (TD-ADH) of Amycolatopsis
      methanolica could be resolved into three protein components, which have been
      purified. Each of the components has the ability to reconstitute TD-ADH activity
      when combined with the other two. Component 1 is identical to the previously
      characterized methanol:N,N'-dimethyl-4-nitrosoaniline oxidoreductase (MNO), a
      decameric protein with 50-kDa subunits, each carrying a tightly bound NADPH.
      Component 2 is a high molecular mass (> 640 kDa) protein with subunits of 44 kDa
      and 72 kDa, and which possesses a low tetrazolium-dye-linked NADH dehydrogenase
      activity. The protein contains a yellow chromophore of unknown identity.
      Component 3 is a low molecular mass (15 kDa) protein containing a 5'-deazaflavin
      and at least one other low-molecular-mass compound with properties similar, but
      not identical, to those of nicotinamide coenzymes. The results suggest that
      alcohol oxidation by the TD-ADH complex is carried out by component 1 (MNO),
      after which transfer of the reducing equivalents (mediated by component 3) occurs
      to component 2, which (in vitro) is linked to the tetrazolium dye. Fractionation
      of A. methanolica extracts showed that most of the 5'-deazaflavin was present in
      component 3. Other gram-positive bacteria having a TD-ADH complex also produced
      5'-deazaflavin. It is concluded that oxidation of primary aliphatic alcohols by
      A. methanolica, and probably also by other gram-positive bacteria containing MNO
      or TD-ADH, proceeds via TD-ADH. The likeliness of 5'-deazaflavin participation in
      this process is discussed.

PMID- 9249039
TI  - The promoter of the human type I 5'-deiodinase gene--mapping of the transcription
      start site and identification of a DR+4 thyroid-hormone-responsive element.
AB  - The selenoenzyme thyroxine 5'-deiodinase type I deiodinates the prohormone
      thyroxine to the active thyroid hormone 3,3',5-triiodothyronine. It is thus one
      of the key enzymes involved in the triiodothyronine-mediated control of growth,
      differentiation and basal metabolism in vertebrates. We report here the
      identification of the transcription start site and the cloning of 1500 bases of
      the upstream regulatory region of the human 5'-deiodinase gene. They contain a
      complex triiodothyronine-responsive element at nucleotides -696 to -673,
      consisting of an ideal direct repeat (DR) of two AGGTCA half-sites with a spacing
      of four nucleotides (DR+4) and a third putative AGTTCA half-site with a spacing
      of another two nucleotides (DR+2). The whole DR+4+2 specifically bound to thyroid
      hormone receptor and retinoid X receptor in electrophoretic mobility shift
      assays. The DR+4+2 mediates triiodothyronine-responsiveness in cotransfection
      experiments of constructs containing the 5'-deiodinase upstream promoter and
      enhancer region fused to luciferase or chloramphenicol acetyltransferase reporter
      genes with expression plasmids of thyroid hormone receptor subtypes. Also, an
      about 2.5-fold induction of the 5'-deiodinase-promoter-luciferase-reporter
      construct by all-trans retinoic acid was observed in a cotransfection assay with
      retinoic acid receptors. Point mutation analysis of the DR+4+2 type hormone
      responsive element, however, revealed that it does not alone mediate the retinoic
      acid effect. The transcription start point of the 5'-deiodinase gene was mapped
      to nucleotides -23 and -24. No CAAT or TATA box is located within the usual
      distance to the transcription initiation site. Two GC boxes were found at
      nucleotides -68 to -63 and -39 to -34. Transfection analysis revealed that the
      proximal 105 nucleotides in the 5'-flanking region of the 5'-deiodinase gene act
      as a functional core promoter. This data indicates that triiodothyronine, the end
      product of thyroid hormone synthesis, positively regulates one of the key enzymes
      in its production.

PMID- 9249040
TI  - Kinase-deficient forms of Jak1 and Tyk2 inhibit interferon alpha signaling in a
      dominant manner.
AB  - Signaling by interferon alpha (IFN alpha), an extracellular factor that mediates
      a number of anti-viral and growth-suppressive effects, requires two members of
      the Janus family of tyrosine kinases (JAK family): Jak1 and Tyk2. IFN alpha
      treatment of cells induces the rapid tyrosine phosphorylation of these two
      kinases, two subunits of the IFN alpha receptor, and two members of the signal
      transducer and activator of transcription (STAT) family of latent transcription
      factors. These proteins are believed to be direct substrates of one or both JAKs.
      Though the requirement for both Jak1 and Tyk2 in the IFN alpha-signaling cascade
      is well established, the order of activation and the relative contribution of the
      two kinases has not been elucidated completely. To address these questions, we
      have employed kinase-deficient mutants of both enzymes. Both mutant kinases
      suppress transcriptional activation as measured by an IFN alpha-dependent
      reporter-gene assay. Furthermore, in transient-transfection assays, the kinase
      deficient versions of Tyk2 and Jak1 can act independently to inhibit STAT
      phosphorylation. Thus, kinase-deficient versions of JAK can act in a dominant
      negative fashion to suppress IFN alpha signaling. The effects of the
      overexpressed mutant kinases on the phosphorylation of the kinases themselves,
      however, are unequal, suggesting that Jak1 functions upstream of Tyk2.

PMID- 9249041
TI  - Inositol phospholipid 3-kinase is activated by cellular stress but is not
      required for the stress-induced activation of glucose transport in L6 rat
      skeletal muscle cells.
AB  - A characteristic response of cells subjected to a stress stimulus is a rapid
      activation of cellular glucose transport. The mechanisms governing this increase
      in glucose transport are poorly understood, but it has been suggested that the
      response may involve the intracellular-signaling components that also participate
      in the hormonal activation of glucose transport. In skeletal muscle and fat
      tissue, inositol phospholipid 3-kinase plays an integral role in the regulation
      of both basal and insulin-stimulated glucose transport. In this study, we have
      investigated whether inositol phospholipid 3-kinase is activated by chemical
      stress and, if so, whether it has a role to play in the stress-induced increase
      in glucose transport in L6 muscle cells. Furthermore, we have attempted to assess
      the basis by which inositol phospholipid 3-kinase may participate in the
      regulation of basal glucose transport. Acute exposure (30 min) of L6 muscle cells
      to 0.5 mM arsenite induced an 80% stimulation in glucose transport. This
      activation was due to a rise in the number of cell-surface glucose transporters,
      based on an increase in the Vmax of glucose transport and the observation that
      arsenite increases the plasma membrane content of GLUT1 and GLUT4 glucose
      transporters by 95% and 60%, respectively, from an intracellular compartment.
      Arsenite induced rapid activation (< 2 min) of inositol phospholipid 3-kinase
      with an approximately fourfold increase in phosphatidylinositol 3,4,5
      trisphosphate (PtdIns3,4,5P3). In contrast, phosphatidylinositol 3-phosphate
      (PtdIns3P) levels were unaffected. Prior treatment of L6 cells with 100 nM
      wortmannin suppressed the arsenite-induced increase in PtdIns3,4,5P3 and reduced
      the cellular content of PtdIns3P by 50%. Under these conditions however,
      wortmannin failed to prevent the stress-induced activation of glucose transport,
      but suppressed basal glucose transport by 60% with an IC50 of about 10 nM. In the
      absence of arsenite, wortmannin caused a dose-dependent inhibition in the
      cellular levels of PtdIns3P and PtdIns3,4,5P3 with IC50 values of about 10 nM and
      100 nM, respectively. In summary, the present results demonstrate that chemical
      stress activates inositol phospholipid 3-kinase and glucose transport in L6
      muscle cells, but unlike the hormonal responses of these cells the activation of
      inositol phospholipid 3-kinase is not responsible for the stress-induced increase
      in glucose transport. This implies that stress-induced and hormonal stimulated
      increases in PtdIns3,4,5P3 levels are functionally distinct. By contrast, the
      maintenance of PtdIns3P levels, presumably involving a PtdIns-specific,
      wortmannin-sensitive inositol phospholipid 3-kinase may be required to support
      basal glucose transport.

PMID- 9249042
TI  - The ribosomal-RNA-processing pathway in Schizosaccharomyces pombe.
AB  - In all cells, a long precursor RNA is processed into mature rRNAs for ribosome
      biogenesis. In eukaryotes, the complexity and speed of the overall process often
      has made it difficult to establish finer details of the maturation pathway. Since
      phylogenetic comparisons can provide evidence for critical events, the major rRNA
      processing pathway for the yeast Schizosaccharomyces pombe was determined using
      primer extension, nuclease protection and Northern-hybridisational analyses.
      Transcript mapping of the 5' external transcribed spacer revealed six cleavage
      sites which occur upstream of the mature 18S termini. Two of these sites as well
      as a site adjacent to the 18S termini are complementary to conserved Box
      sequences in the S. pombe U3 small nucleolar RNA. Transcript mapping of the
      internal transcribed spacers (1 and 2) suggest similar maturation schemes for the
      two spacers, in which an initial endonuclease cleavage is followed by processing
      to the mature termini. The mature 5' termini of 25S rRNA appear to be
      heterogeneous in S. pombe, as has been demonstrated for 5.8S rRNA, suggesting an
      essential limiting structure in the ribosome-integrated mature RNA. Together with
      our previous analysis of the 3' external spacer region, the results reveal the
      major processing pathway for S. pombe and further support a maturation process
      which acts as a quality assurance mechanism.

PMID- 9249043
TI  - Electron-transfer properties of Pseudomonas aeruginosa [Lys44, Glu64]azurin.
AB  - In the hydrophobic patch of azurin from Pseudomonas aeruginosa, an electric
      dipole was created by changing Met44 into Lys and Met64 into Glu. The effect of
      this dipole on the electron-transfer properties of azurin was investigated. From
      a spectroscopic characterization (NMR, EPR and ultraviolet-visible) it was found
      that both the copper site and the overall structure of the [Lys44, Glu64]azurin
      were not disturbed by the two mutations. A small perturbation of the active site
      at high pH, similar to that observed for [Lys44]azurin, occurs in the double
      mutant. At neutral pH the electron-self-exchange rate constant of the double
      mutant shows a decrease of three orders of magnitude compared with the wild-type
      value. The possible reasons for this decrease are discussed. Electron transfer
      with the proposed physiological redox partners cytochrome c551 and nitrite
      reductase have been investigated and the data analyzed in the Marcus framework.
      From this analysis it is confirmed that the hydrophobic patch of azurin is the
      interaction site with both partners, and that cytochrome c551 uses its
      hydrophobic patch and nitrite reductase a negatively charged surface area for the
      electron transfer.

PMID- 9249044
TI  - Protection of mice against a lethal influenza challenge by immunization with
      yeast-derived recombinant influenza neuraminidase.
AB  - The head domain of recombinant neuraminidase of A/Victoria/3/75 influenza virus
      was produced in a secreted form in the methylotrophic yeast Pichia pastoris using
      the P. pastoris alcohol oxidase 1 promoter and the Saccharomyces cerevisiae alpha
      mating-factor signal sequence. Cultures in shake flasks provided expression
      levels of approximately 2.5-3 mg/l. Recombinant neuraminidase was purified from
      the culture medium to over 99% homogeneity. Although P. pastoris-secreted
      products are believed to carry shorter N-linked carbohydrate side chains than
      glycoproteins of S. cerevisiae, secreted neuraminidase was hyperglycosylated,
      with N-glycans of the high-mannose type containing up to 30-40 mannose residues.
      N-glycans were phosphorylated and only partially sensitive to alpha-mannosidase
      treatment. Balb/c mice immunized three times with 2 microg purified recombinant
      neuraminidase were 50% protected against a lethal challenge of mouse-adapted
      homologous virus; removal of glycosylation at the top of neuraminidase resulted
      in improved protection. The results provide a system for the production of an
      effective recombinant influenza vaccine that can easily be scaled up.

PMID- 9249045
TI  - Secondary structure and shape of plasma sex steroid-binding protein--comparison
      with domain G of laminin results in a structural model of plasma sex steroid
      binding protein.
AB  - We have analyzed the secondary structure, shape and dimensions of plasma sex
      steroid-binding protein (SBP) by CD, size-exclusion chromatography and electron
      microscopy. CD spectra show extrema at 186 nm and 216 nm characteristic for beta
      sheet structures. Analysis with different algorithms indicates 15% alpha-helix,
      43% beta-sheet and 10-16% beta-turn structures. An irreversible structural change
      is observed upon heating above 60 degrees C, which correlates with the loss of
      steroid-binding activity. As the SBP sequence shows similarity with domains of
      several multidomain proteins, including laminins, we evaluated the structure of
      domain G of laminin-1. The CD spectrum shows extrema at 200 nm and 216 nm.
      Deconvolution results in 13% alpha-helix, 32% beta-sheet and 15% beta-turn
      structures. Steroid-binding assays indicate that laminin and fragments thereof
      have no activity. Size-exclusion chromatography reveals that SBP has an extended
      shape and can be modeled as a cylinder with a length and diameter of 23 nm and 3
      nm, respectively. This shape and the dimensions are in agreement with the
      appearance on electron micrographs. We propose a model for the structure of SBP
      in which two monomers assemble head to head with the steroid-binding site located
      in the center of the rod-like particle.

PMID- 9249046
TI  - Sequencing, expression and properties of triosephosphate isomerase from Entamoeba
      histolytica.
AB  - We have isolated a cDNA clone of the glycolytic enzyme, triosephosphate isomerase
      (TPI) from Entamoeba histolytica. Degenerate oligonucleotides obtained by reverse
      translation of conserved polypeptide sequences, derived from TPIs of other
      organisms, were used to amplify a 450-bp fragment using E. histolytica cDNA as a
      template. The fragment was used to screen a cDNA library. The isolated cDNA,
      encoding a protein of 261 amino acids, shares 43-52.6% positional identity with
      other known protozoan TPIs. The catalytic residues were conserved; nevertheless,
      several indels occurred at other regions in the protein sequence. The complete
      coding sequence of the E. histolytica TPI gene was cloned into the expression
      vector pRSET and expressed as a wild-type TPI enzyme (E. histolytica TPI) and as
      a fusion protein with an N-terminal tail of six histidine residues E. histolytica
      TPI-His6); both recombinant proteins were purified. Molecular modeling of E.
      histolytica TPI showed an identical topology to the known structures of other TPI
      molecules, but with a remarkable feature; more than 10 inserted residues are
      located in the same region of the molecular surface. Studies were performed to
      detect possible changes that might be caused by the inserted amino acids. The
      catalytic activity and oligomeric state of the purified protein were similar to
      that reported for TPI from other sources. In contrast, stability towards
      dilution, as well as thermal inactivation and unfolding assays, showed that E.
      histolytica TPI is significantly more stable towards denaturation than
      Trypanosoma brucei TPI.

PMID- 9249047
TI  - 1.8-A crystal structure of the catalytic domain of human neutrophil collagenase
      (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed
      side inhibitor with a distinct selectivity profile.
AB  - Matrix metalloproteinases (MMP) are zinc endopeptidases involved in tissue
      remodelling. They have been implicated in a series of pathologies, including
      cancer, arthritis, joint destruction and Alzheimer's disease. Human neutrophil
      collagenase represents one of the three interstitial collagenases that cleave
      triple-helical collagen of type I, II and III. Its catalytic domain (residues
      Phe79-Gly242) has been heterologously expressed in Escherichia coli and
      crystallized as a non-covalent complex with the hydroxamate inhibitor BB-1909,
      which has distinct selectivity against different MMP, in a crystal form. The
      crystal structure, refined to 0.18-nm resolution, shows that BB-1909 is a right
      hand-side inhibitor that binds to the S1'-S3' subsites and coordinates to the
      catalytic Zn2+ in a bidentate manner via the hydroxyl and carbonyl oxygen atoms
      of the hydroxamate group in a similar manner to batimastat. The collagenase/BB
      1909 complex is described in detail and compared with the collagenase/batimastat
      complex. These studies provide information on MMP specificity and thus may assist
      the development of more-selective MMP inhibitors.

PMID- 9249048
TI  - The enzymology of lysine catabolism in rice seeds--isolation, characterization,
      and regulatory properties of a lysine 2-oxoglutarate reductase/saccharopine
      dehydrogenase bifunctional polypeptide.
AB  - In plant, the catabolism of lysine has only been studied in some detail in maize.
      The enzymes lysine 2-oxoglutarate reductase (also known as lysine alpha
      ketoglutarate reductase; LOR) and saccharopine dehydrogenase (SDH), which convert
      lysine into saccharopine, and saccharopine into glutamic acid and 2-aminoadipate
      6-semialdehyde, respectively, were isolated from immature rice seeds and
      partially purified through a three-step purification procedure involving ammonium
      sulphate precipitation, and anion-exchange and gel-filtration chromatographies,
      leading to a final yield of 30% for LOR and 24% for SDH. The molecular masses
      estimated by gel-filtration chromatography on a Sephacryl S200 column and by
      native non-denaturing PAGE using Ferguson plots were 203 kDa for both enzymes by
      gel-filtration and 202 kDa for both enzymes by native non-denaturing PAGE. A
      second band of LOR and SDH activities on native gels was observed for both
      enzymes with an estimated molecular mass of 396 kDa, which indicated a multimeric
      structure. Kinetic studies were consistent with an ordered sequence mechanism for
      LOR, where 2-oxoglutarate is the first substrate and saccharopine is the last
      product. The results observed for the LOR/SDH activity ratios during
      purification, the copurification in all three steps, the molecular masses, the
      relative mobilities on native non-denaturing gels and the pI estimated for LOR
      and SDH suggest the existence of a bifunctional polypeptide containing LOR and
      SDH activities.

PMID- 9249049
TI  - Importance of the amino terminus in maintenance of oligomeric structure of sheep
      liver cytosolic serine hydroxymethyltransferase.
AB  - The role of the amino and carboxyl-terminal regions of cytosolic serine
      hydroxymethyltransferase (SHMT) in subunit assembly and catalysis was studied
      using six amino-terminal (lacking the first 6, 14, 30, 49, 58, and 75 residues)
      and two carboxyl-terminal (lacking the last 49 and 185 residues) deletion
      mutants. These mutants were constructed from a full length cDNA clone using
      restriction enzyme/PCR-based methods and overexpressed in Escherichia coli. The
      overexpressed proteins, des-(A1-K6)-SHMT and des-(A1-W14)-SHMT were present in
      the soluble fraction and they were purified to homogeneity. The deletion clones,
      for des-(A1-V30)-SHMT and des-(A1-L49)-SHMT were expressed at very low levels,
      whereas des-(A1-R58)-SHMT, des-(A1-G75)-SHMT, des-(Q435-F483)-SHMT and des-(L299
      F483)-SHMT mutant proteins were not soluble and formed inclusion bodies. Des-(A1
      K6)-SHMT and des-(A1-W14)-SHMT catalyzed both the tetrahydrofolate-dependent and
      tetrahydrofolate-independent reactions, generating characteristic spectral
      intermediates with glycine and tetrahydrofolate. The two mutants had similar
      kinetic parameters to that of the recombinant SHMT (rSHMT). However, at 55
      degrees C, the des-(A1-W14)-SHMT lost almost all the activity within 5 min, while
      at the same temperature rSHMT and des-(A1-K6)-SHMT retained 85% and 70% activity,
      respectively. Thermal denaturation studies showed that des-(A1-W14)-SHMT had a
      lower apparent melting temperature (52 degrees C) compared to rSHMT (56 degrees
      C) and des-(A1-K6)-SHMT (55 degrees C), suggesting that N-terminal deletion had
      resulted in a decrease in the thermal stability of the enzyme. Further, urea
      induced inactivation of the enzymes revealed that 50% inactivation occurred at a
      lower urea concentration (1.2+/-0.1 M) in the case of des-(A1-W14)-SHMT compared
      to rSHMT (1.8+/-0.1 M) and des-(A1-K6)-SHMT (1.7+/-0.1 M). The apoenzyme of des
      (A1-W14)-SHMT was present predominantly in the dimer form, whereas the apoenzymes
      of rSHMT and des-(A1-K6)-SHMT were a mixture of tetramers (approximately 75% and
      approximately 65%, respectively) and dimers. While, rSHMT and des-(A1-K6)-SHMT
      apoenzymes could be reconstituted upon the addition of pyridoxal-5'-phosphate to
      96% and 94% enzyme activity, respectively, des-(A1-W14)-SHMT apoenzyme could be
      reconstituted only up to 22%. The percentage activity regained correlated with
      the appearance of visible CD at 425 nm and with the amount of enzyme present in
      the tetrameric form upon reconstitution as monitored by gel filtration. These
      results demonstrate that, in addition to the cofactor, the N-terminal arm plays
      an important role in stabilizing the tetrameric structure of SHMT.

PMID- 9249050
TI  - Molecular chaperones protect catalase against thermal stress.
AB  - Lenticular alpha-crystallin is generally thought of as having limited chaperone
      functions. It can efficiently suppress the aggregation of proteins but is unable
      to promote the functional refolding of proteins after denaturation in many
      systems unlike other molecular chaperones. However, it has been reported that
      alpha-crystallin, along with the small heat-shock proteins, is able to promote
      the functional refolding of some enzymes after thermal and chemical denaturation.
      These chaperones are also able to confer protection against the thermal
      inactivation of these enzymes. In results presented here, we demonstrate that
      alpha-crystallin, along with chaperonin 60 (GroEL), was able to provide
      statistically significant and specific protection against catalase thermal
      inactivation at stoichiometrical concentrations. The small heat-shock protein,
      heat-shock protein 25 (Hsp25), was unable to confer any such protection. alpha
      Crystallin however was unable to promote the functional refolding of thermally
      inactivated catalase. alpha-Crystallin and Hsp25 both efficiently suppressed the
      thermal aggregation of catalase. A high-molecular-mass (HMM) complex was only
      observed to develop in solutions containing catalase and alpha-crystallin after
      solutions were 80-fold more concentrated relative to thermal inactivation assay
      conditions prior to incubation. SDS/PAGE analysis confirmed that alpha-crystallin
      had formed a soluble complex with catalase after a period of thermal stress.

PMID- 9249051
TI  - NMR investigations of the role of the sugar moiety in glycosylated recombinant
      human granulocyte-colony-stimulating factor.
AB  - Human granulocyte-colony-stimulating factor (G-CSF) is a hematopoietic growth
      factor that plays a major role in the stimulation of the proliferation and
      maturation of granulocyte neutrophil cells. With the recent increased
      understanding of its biological properties in vivo together with available
      preparations of recombinant human G-CSF, this growth factor has become an
      essential agent for clinical applications. The presence of an O-linked
      carbohydrate chain at position 133 greatly improves the physical stability of the
      protein. To clarify the molecular basis for the stabilisation effect of
      saccharide moieties on human G-CSF the whole glycoprotein expressed in CHO cells
      has been investigated by means of two 1H-NMR-spectroscopy and two 1H-detected
      heteronuclear 1H-13C experiments at natural abundance, and compared with the non
      glycosylated form. The present NMR study reports assignments of 1H and 13C
      resonances of the bound saccharidic chain NeuNAc(alpha2-3)Gal(beta1
      3)[NeuNAc(alpha2-6)]GalNAc, where NeuNAc represents N-acetylneuraminic acid, and
      demonstrates the alpha-anomeric configuration of the N-acetylgalactosamine
      threonine linkage. It also provides results suggesting that the carbohydrate
      moiety reduces the local mobility around the glycosylation site, which could be
      responsible for the stabilising effect observed on the glycoprotein.

PMID- 9249052
TI  - Intermolecular cleavage by the newt ribozyme.
AB  - To analyse the trans-cleavage activity of the hammerhead ribozyme occurring in
      the ovary of the newt (Notophthalmus, Triturus) in more detail, six synthetic
      ribozymes representing natural and modified hammerhead sequences were tested with
      both short oligoribonucleotides and long transcripts as substrates. The same
      analysis was also performed with the monomer (330 nucleotides) newt ribozyme and
      variants thereof. None of the ribozymes comprising the newt natural sequence
      showed activity under multiple turnover conditions, regardless of sequence
      changes in stem and loop II. With excess of ribozyme, the same ribozymes cleaved
      only to a limited extent a short substrate and extremely poorly a target site
      embedded within a long transcript. The addition of whole ovary cell extract had
      little influence on cleavage activity of short substrates. However, sequence
      changes in stems I and III to target different sequences considerably improved
      cleavage ability of the ribozymes under all conditions used. An RNA secondary
      structure folding program showed that ribozymes with the natural newt sequence
      did not fold in a hammerhead structure whereas those with the changes in stem I
      and III did. These results suggest that the sequence of the stems I and III
      impairs the assembly of the newt ribozyme into a bimolecular hammerhead complex
      in vitro and that proteins present in the ovaries do not facilitate activity.

PMID- 9249053
TI  - Structural studies on the short-chain lipopolysaccharide of Vibrio cholerae O139
      Bengal.
AB  - A Vibrio cholerae O139 strain, MO10-T4, lacking capsular polysaccharide, produces
      a short-chain lipopolysaccharide (LPS), similar to enterobacterial SR strains. It
      was studied by acidic and alkaline degradation, dephosphorylation, sugar and
      methylation analysis, high-performance anion-exchange chromatography, one- and
      two-dimensional 1H-, 13C-, and 31P-NMR spectroscopy, and electrospray ionization
      mass spectrometry. The following structure was proposed for the core region of
      the LPS: [structure: see text] where PEtn stands for 2-aminoethyl phosphate, Fru
      for fructose, Hep for L-glycero-D-manno-heptose, and Kdo for 3-deoxy-D-manno
      octulosonic acid; unless otherwise stated, the monosaccharide residues are D and
      present in the pyranose form. An O-acetyl group is present on a secondary
      position, tentatively O4 of the alpha-linked glucosyl group. Some LPS species
      contain an additional putative fructose residue whose location remains unknown.
      An O139-negative mutant strain, Bengal-2R, derived from V. cholerae O139, has
      also been investigated and shown to produce an O-antigen-lacking LPS similar to
      those from enterobacterial R strains, some of the LPS species containing the same
      core region as the strain MO10-T4 LPS and the other lacking the lateral heptose
      residue. The carbohydrate backbone core structure is the same for the V. cholerae
      O139 and V. cholerae O1 LPS, thus confirming the close relation between these
      bacteria; however, the 2-aminoethyl phosphate, the O-acetyl group, and the second
      fructose residue have not been reported for the O1 LPS. In the V. cholerae O139
      strain MO10-T4 LPS, a short O-side chain is attached at position 3 of the 7
      substituted heptose residue and has the same structure as one repeating unit of
      the V. cholerae O139 capsular polysaccharide. Some details of the structure
      proposed are at variance with those recently published for another V. cholerae
      O139 strain [Cox, A. D., Brisson, J.-R., Varma, V. & Perry, M. B. (1996)
      Carbohydr. Res. 290, 43-58; Cox, A. D. & Perry, M. B. (1996) Carbohydr. Res. 290,
      59-65.]

PMID- 9249054
TI  - Inhibition of translation by mRNA encoding NIPP-1, a nuclear inhibitor of protein
      phosphatase-1.
AB  - Transient transfection of COS-1 cells with an expression vector for NIPP-1, a
      nuclear subunit of protein phosphatase-1, did not result in an overexpression of
      NIPP-1 protein, although the levels of mRNA encoding NIPP-1 increased
      dramatically. Moreover, high concentrations of NIPP-1 mRNA inhibited the
      translation in reticulocyte lysates of various unrelated mRNAs. This inhibition
      of translation was caused by the NIPP-1 messenger and not by the translation
      product, since mutation of the start codon abolished NIPP-1 protein production,
      but had no influence on the translational inhibition. Analysis of deletion
      mutants showed that the inhibition was mediated by a 0.5-kb fragment in the 5'
      end of the NIPP-1 mRNA. This region, when inserted in the 5'-untranslated region
      of the beta-galactosidase messenger, inhibited the translation of beta
      galactosidase mRNA in COS-1 cells. A predicted highly stable secondary structure
      deltaG = -239.5 kJ/mol) is present between residues 300 and 500 of NIPP-1 mRNA.
      The possible importance of this structure in the translational inhibition is
      discussed.

PMID- 9249055
TI  - Characterization of the interaction between the Staphylococcus aureus clumping
      factor (ClfA) and fibrinogen.
AB  - The ability of Staphylococcus aureus to adhere to adsorbed fibrinogen and fibrin
      is believed to be an important step in the initiation of biomaterial and wound
      associated infections. In this study, we show that the binding site in fibrinogen
      for the recently identified S. aureus fibrinogen-binding protein clumping factor
      (ClfA) is within the C-terminus of the fibrinogen gamma chain. S. aureus Newman
      cells expressing ClfA adhered to microtitre wells coated with recombinant
      fibrinogen purified from BHK cells, but did not adhere to wells coated with a
      purified recombinant fibrinogen variant where the 4 C-terminal residues of the
      gamma chain were replaced by 20 unrelated residues. In addition, a synthetic
      peptide corresponding to the 17 C-terminal amino acids of the fibrinogen gamma
      chain effectively inhibited adherence of ClfA-expressing cells to fibrinogen. In
      western ligand blots, a recombinant truncated ClfA protein called Clf33 (residues
      221-550) recognized intact recombinant fibrinogen gamma chains, but failed to
      recognize recombinant fibrinogen gamma chains where the 4 C-terminal amino acids
      were altered by deletion or substitution. Previous studies have shown that the C
      terminal domain of fibrinogen gamma chains contains a binding site for the
      integrin alphaIIb beta3 (glycoprotein gpIIb/IIIa) receptor on platelets
      [Kloczewiak, M., Timmons, S., Bednarek, M. A., Sakon, M. & Hawiger, J. (1989)
      Biochemistry 28, 2915-1919; Farrell, D. H., Thiagarajan, P., Chung, D. W. &
      Davie, E. W. (1992) Proc. Natl. Acad. Sci. USA 89, 10729-10732; Hettasch, J. M.,
      Bolyard, M. G. & Lord, S. T. (1992) Thromb. Haemostasis 68, 701-706]. We now show
      that Clf33 inhibits ADP-induced, fibrinogen-dependent platelet aggregation in a
      concentration-dependent manner and inhibits adhesion of platelets to immobilized
      fibrinogen under fluid shear stress, indicating that the binding sites for the
      platelet integrin and the staphylococcal adhesin overlap. The interaction between
      Clf33 and fibrinogen was further characterized using the BIAcore biosensor. When
      soluble Clf33 was allowed to bind to immobilized fibrinogen, a Kd of 0.51 +/-
      0.19 microM was experimentally determined using equilibrium binding data. It was
      also shown that the synthetic C-terminal gamma-chain peptide effectively
      inhibited this interaction.

PMID- 9249056
TI  - The signal transducer gp130--bacterial expression, refolding and properties of
      the carboxy-terminal domain of the cytokine-binding module.
AB  - Gp130 is the signal transducing receptor subunit of the so-called interleukin-6
      type cytokines. This transmembrane protein is a member of the cytokine-receptor
      superfamily predicted to consist of six fibronectin-type-III-like domains in its
      extracellular part. The second and the third domain constitute the so-called
      cytokine-binding module. Domain 2 is characterized by a set of four conserved Cys
      residues, domain 3 by a conserved WSXWS motif. As a first approach to a more
      detailed characterization of the cytokine-binding domains of human gp130, we have
      expressed in Escherichia coli two forms of domain 3 differing in length. Both
      proteins were purified and refolded in a single step applying size-exclusion
      chromatography. According to the rotational correlation times deduced from
      fluorescence anisotropy decay, they do not form aggregates. CD and fluorescence
      spectroscopy were used to study thermal unfolding and denaturation by guanidinium
      hydrochloride. It was shown that N- and C-terminal extension by residues of the
      adjacent hinge regions substantially increase the thermal stability of the
      domain, which is conceivable from a molecular model. These results are the basis
      for further structural investigation by NMR spectroscopy.

PMID- 9249057
TI  - Electrostatic effects of smooth muscle calponin on actin assembly.
AB  - The contribution of electrostatic interactions to the effects of chicken gizzard
      calponin on the kinetics of actin polymerization and the bundling of F-actin were
      characterized by a combination of fluorescence, light-scattering, co
      sedimentation, and electron-microscopic methods. Stoichiometric amounts of
      calponin accelerate actin polymerization in low-ionic-strength solutions, but
      this effect is diminished at [KCI] = 150 mM. At low ionic strengths, micromolar
      concentrations of calponin induce the formation of large bundles of actin
      filaments, and lower concentrations of calponin quench the fluorescence of pyrene
      labeled F-actin. The latter effect is related to binding of calponin to F-actin
      rather than to bundling of the filaments. The concentration of calponin required
      to bundle a fixed concentration of actin filaments increases with increasing
      ionic strength, as the average diameter of the bundles decreases. Millimolar
      concentrations of ATP, GTP or ITP are equally efficient at dispersing actin
      bundles to single filaments or smaller aggregates, even though a significant
      fraction of calponin remains bound to F-actin. Our findings show that the binding
      of calponin to actin is determined at least in part by electrostatic
      interactions, and that the polycationic nature of calponin is primarily
      responsible for the formation of F-actin bundles via its ability to reduce the
      electrostatic repulsion between the negatively charged actin filaments.

PMID- 9249058
TI  - Transcriptional and translational adjustments of psbA gene expression in mature
      chloroplasts during photoinhibition and subsequent repair of photosystem II.
AB  - The D1 reaction centre protein of photosystem II (PSII), encoded by the plastid
      psbA gene, has the highest turnover rate of all thylakoid proteins, due to light
      induced damage to D1. The expression of the psbA gene was studied in chloroplasts
      of fully developed pea (Pisum sativum L.) leaves during high-light
      photoinhibitory treatment and subsequent restoration of PSII function at low
      light. psbA transcript levels were determined and the translational activity was
      followed by in vivo pulse-labelling, by in vitro translations with intact
      chloroplasts, and by run-off translations on isolated thylakoid membranes. PSII
      photochemical efficiency was determined in vivo by monitoring the ratio of
      variable fluorescence to maximal fluorescence (F(V)/F(M)). Enhanced D1 synthesis
      in pea leaves, upon a shift first from darkness to growth light and subsequently
      to high light, was accompanied by a substantial increase in the total number of
      pshA transcripts and by the accumulation of psbA mRNA x initiation complexes on
      thylakoid membrane. This suggested that high-light illumination increased the
      transcriptional activity of the psbA gene in mature leaves, and that enhanced
      translational initiation of psbA mRNA was followed by docking of the initiation
      complexes to the thylakoid membrane. The high-light-induced increase in the
      number of thylakoid-associated psbA mRNA x initiation complexes, occurred in
      parallel with enhanced in vivo D1 synthesis. This, however, did not result in an
      enhanced accumulation of D1 translation products in in vitro run-off translations
      when pea leaves were shifted from growth light to high light. This may suggest
      that at high light only a portion of thylakoid-associated psbA mRNA can be under
      translational elongation at a given moment. When the leaves were shifted from
      high light to low light to allow repair of PSII, thylakoid-associated psbA mRNA
      was rapidly released from the membrane and the high-light-induced pool of psbA
      transcripts was degraded. The synthesis of the D1 protein decreased on the same
      time scale. However, the restoration of PSII photochemical function, measured as
      F(V)/F(M), took a substantially longer time. It is concluded that during changing
      light conditions, mature leaves are able to adjust psbA gene expression both at
      the transcriptional and at the translational level.

PMID- 9249059
TI  - Distinct repression of translation by wortmannin and rapamycin.
AB  - The role of phosphatidylinositol 3-kinase and FK506-binding protein rapamycin
      associated protein (FRAP) in translational control has been examined by treating
      RD-rhabdomyosarcoma cells with wortmannin and rapamycin and studying the effects
      on cell-growth, translation initiation, and protein synthesis. Whereas wortmannin
      and rapamycin exhibit subtle effects on global translation, examination of
      individual mRNAs in sucrose gradients and of individual proteins in two
      dimensional polyacrylamide gels reveals that wortmannin and rapamycin exhibit
      distinct effects on the translation of individual mRNAs. Wortmannin represses the
      synthesis of a third of cellular proteins, whereas rapamycin affects a subset of
      these proteins. Since ribosomal protein S6 was rapidly dephosphorylated following
      wortmannin and rapamycin treatment, and the phosphorylation status of the
      eukaryotic initiation factor 4E was unchanged, our data imply that the p70
      signalling pathway has at least one branch-point upstream of FRAP leading to an
      additional route of translational control.

PMID- 9249060
TI  - Cloning and analysis of the cDNA encoding the rod G-protein transduction alpha,
      beta1 and gamma1 subunits from the canine retina.
AB  - The canine (Canis familiaris) retinal rod transducin (G(T)) alpha, beta1 and
      gamma1 subunits were sequenced. Cloning of the cDNAs was accomplished by
      polymerase chain reaction (PCR) using degenerate and wild type retinal cDNA
      libraries as templates. The deduced amino acid sequences were highly similar to
      rod transducins from other species: G(T alpha) differed by 5 amino acids from the
      corresponding human sequence, whereas beta1 and gamma1 were identical to human
      sequences. The coding sequence of rod transducin was evaluated as a possible
      cause for the recessively inherited retinal rod-cone degeneration: there were no
      nucleotide differences between the wild type and retinal degenerate strains.

PMID- 9249061
TI  - Analysis of the promoter and transcription start sites of the human
      thrombospondin 2 gene (THBS2).
AB  - To identify features of the human thrombospondin 2 gene (THBS2) important for
      regulation of expression, the sequences of 5 kb of the promoter/5' flank and 3 kb
      of transcribed and intronic DNA were determined. Two repetitive sequences were
      found: an MLT1c element located 2.2 kb 5' of exon 1 and, further 5', 1.8 kb of a
      Tigger1 element. Putative transcription factor binding sites that might be
      significant for THBS2 regulation included p53, NF-kappaB, Spl, Myc-CF1, NF-Y,
      CF1, AP1, and GATA sites. Alignment of the promoter/5' flank sequence with the
      mouse Thbs2 promoter revealed 78% identity for a 450 bp region immediately
      upstream from the mouse transcription start site. No significant homology was
      detected between the human thrombospondin 2 and thrombospondin 1 promoters.
      Comparison of the THBS2 genomic and cDNA sequences revealed that, in contrast to
      Thbs2, exon 1 is divided into exons 1A and 1B by a small (93 bp) intron. The
      transcription start site was investigated by a PCR procedure and by 5' RACE, and
      yielded a size for exon 1A of at least 186 bp. Tissue-specific differences in
      transcription start sites were found, with transcript lengths in the order: fetal
      lung > adult lung > fetal brain. These results suggest that tissue-specific
      differences in expression of the THBS2 gene may be determined, in part, by
      selection of the transcription start site and resulting differences in the 5'
      untranslated region.

PMID- 9249062
TI  - Sequence and genetic analysis of the hemin storage (hms) system of Yersinia
      pestis.
AB  - We have sequenced a region from the pigmentation (pgm) locus of Yersinia pestis
      KIM6+ that is identified with the exogenous hemin storage (Hms+) phenotype in
      cells grown at 26 but not at 37 degrees C. The hmsHFRS locus encodes a putative
      polycistronic operon, with hmsH encoding an outer membrane protein with a deduced
      molecular mass of 93.4/89.5 (unprocessed/processed) kDa. The mature HmsH 788 aa
      polypeptide has a pI of 4.99. The hmsF gene has an open reading frame of 654 aa,
      encoding a 74.6/72.2 kDa OM protein with a pI of 5.16 when processed. A deduced
      423 aa, 52 kDa protein with a pI of 10.83 is encoded by hmsR. HmsR has a basic,
      hydrophilic, and alpha-helical carboxyl terminus; 13 aa at the amino-terminal end
      and a 'KRKRAR' sequence at the carboxy-terminal end are essential for an Hms+
      phenotype. The hmsS gene encodes a hypothetical 155 aa, 17.5 kDa protein with a
      pI of 6.68. Hms- Y. pestis strain M23-2 transformed with the cloned hmsHFRS locus
      developed an Hms(c) phenotype (Hms+ at 26-37 degrees C) due to mutations in genes
      outside the pgm locus.

PMID- 9249063
TI  - Sequencing and analysis of the Thermus thermophilus ribosomal protein gene
      cluster equivalent to the spectinomycin operon.
AB  - To assess the organization of the Thermus thermophilus ribosomal protein genes, a
      fragment of DNA containing the complete S10 region and ten ribosomal protein
      genes of the spc region was cloned, using an oligonucleotide coding for the N
      terminal amino acid (aa) sequence of T. thermophilus S8 protein as hybridization
      probe. The nucleotide sequence of a 4290 bp region between the rps17 and rpl15
      genes was determined. Comparative analysis of this gene cluster showed that the
      gene arrangement (S17, L14, L24, L5, S14, S8, L6, L18, S5, L30 and L15) is
      identical to that of eubacteria. However, T. thermophilus ribosomal protein genes
      corresponding to the Escherichia coli S10 and spc operons are not resolved into
      two clusters: the stop codon of the rps17 gene (the last gene of the S10 operon
      in E. coli) and the start codon of the rpl14 gene (the first gene of the spc
      operon in E. coli) overlap. Most genes, except the rps14-rps8 intergenic spacer
      (69 bp), are separated by very short (only 3-7 bp) spacer regions or partially
      overlapped. The deduced aa sequences of T. thermophilus proteins share about 51
      100% identities with the sequences of homologous proteins from thermophile
      Thermus aquaticus and Thermotoga maritima and 27-70% identities with the
      sequences of their mesophile counterparts.

PMID- 9249064
TI  - Cloning and characterization of the mouse homolog of the human A6 gene.
AB  - The mouse homolog of a novel human protein tyrosine kinase encoding gene, A6, was
      cloned and characterized. The human A6 cDNA is unique in that its gene product
      exhibited in vitro kinase activity but its predicted amino acid (aa) sequence
      revealed no consensus motifs commonly found within the kinase domain of protein
      kinase family members. Here, we isolated a mouse A6 cDNA clone from a murine
      myeloid progenitor 32D cell library using a 1.1 kb cDNA probe containing the
      entire human A6 open reading frame (ORF). Determination of the mouse A6 cDNA
      nucleotide (nt) sequence revealed an ORF of 1050 nt encoding a protein of 350 aa
      and a molecular mass of 40,201 Da. The mouse and human A6 gene products shared
      93% identity. In vitro translation, as well as immunoprecipitation of 32D cell
      lysates confirmed expression of mouse A6 as a 40 kDa protein. Northern blot
      analysis of total RNA from mouse cell lines derived from diverse tissues
      including NIH 3T3 fibroblasts, L cell fibroblasts, C2C12 myoblasts, M1
      myeloblasts, BALB/MK cells, 70Z/3 preB lymphocytes, and p388D1 monocytes
      demonstrated widespread A6 mRNA expression. A6 mRNA was also ubiquitously
      expressed at varying levels in all tissues examined. The identification of a
      potential actin/phosphoinositide binding domain and consensus phosphorylation
      sites, coupled with A6's expression in a variety of cell types suggest that the
      A6 gene product may play a role in basic cellular processes.

PMID- 9249065
TI  - Asymmetrical progression of replication forks just after initiation on Mycoplasma
      capricolum chromosome revealed by two-dimensional gel electrophoresis.
AB  - Previously, we mapped the replication initiation site of the Mycoplasma
      capricolum chromosome into a region containing the dnaA gene [M. Miyata et al.,
      1993a. Nucleic Acids Res. 21, 4816-4823]. In this study, various regions
      including this functional domain were analyzed by two complementary two
      dimensional (2D) gel electrophoretic methods. Sizes of nascent strands in a 10.7
      kb and a 5.6-kb region were examined by a neutral/alkaline (N/A) method. The
      shortest nascent strand was detected in an 875-bp region composed of the 3' end
      of the dnaA gene and its downstream non-coding sequence. The shortest nascent
      strand detected became longer in an asymmetrical manner as position of the probe
      became further from the putative initiation site in both directions. The
      intermediate forms of eight regions restricted at different sites were examined
      by a neutral/neutral (N/N) method. Bubble arcs were observed in four regions
      including the 875-bp region. The region containing the 875-bp region at about its
      center showed an asymmetrical arc, although that containing the 875-bp region at
      its end showed a symmetrical arc. These results show that the replication forks
      develop in the 875-bp region and proceed bidirectionally in an asymmetrical
      manner around the initiation site. The results of N/A analysis of the 5.6-kb
      region showed a shift of intensity in the nascent strand signal, which suggests
      an upshift of fork progression velocity.

PMID- 9249066
TI  - Leukemia breakpoint region in 3q21 is gene rich.
AB  - Rearrangements of the long arm of human chromosome 3, including reciprocal
      translocations, inversions and deletion/duplication of bands 3q21-3q26, as well
      as deletions of 3q21 and reciprocal translocations between 3q21 and other
      chromosomes, are well documented in leukemia. Previous studies showed that the
      breakpoints within 3q21 cluster within a 10-40 kb region but no candidate genes
      were described. In this work, we have identified partial cDNAs corresponding to
      five to nine new transcripts from an 80 kb P1 clone that spans ten breakpoints.
      These transcripts, with one exception, appear to be expressed only at low levels
      in the set of cancer cell lines examined. Four transcripts are located between
      the previously mapped Ribophorin I gene and the most centromeric breakpoint;
      three map directly within the 20 kb spanning nine independent breakpoints. These
      data (i) show that among characterized leukemia breakpoint regions 3q21 is
      unusually gene rich, (ii) provide new candidates for relevance to leukemia in
      3q21, and (iii) suggest possibilities for chromatin configuration effects.

PMID- 9249067
TI  - Use of polymerase chain reaction to identify a leucyl tRNA in Streptomyces
      coelicolor.
AB  - Polymerase chain reaction (PCR) was used to amplify a fragment of DNA encoding a
      tRNA that recognizes the abundant CUC leucine codon from the chromosome of
      Streptomyces coelicolor. Sequence analysis of the gene, designated leuU,
      indicated that it codes for a tRNA 88 nucleotides in length that shares 75%
      identity with the Escherichia coli tRNA(Leu)CUC, while it shares only 65%
      identity with the only other sequenced leucyl tRNA from S. coelicolor, the bldA
      encoded tRNA(Leu)UUA. Accumulation of the leuU tRNA was examined by Northern blot
      analysis and shown to be present at constant levels throughout growth in contrast
      to the bldA-encoded tRNA which shows a temporal pattern of accumulation [Leskiw
      et al., 1993. J. Bacteriol., 175, 1995-2005].

PMID- 9249068
TI  - Nucleotide sequence of the ermE distal flank of the erythromycin biosynthesis
      cluster in Saccharopolyspora erythraea.
AB  - A 7023 nucleotide BamHI fragment immediately upstream of the eryK gene of the
      erythromycin (Er) biosynthesis cluster in Saccharopolyspora erythraea was
      sequenced. Computer-assisted analysis of this sequence reveals the existence of
      seven ORFs that display the codon preferences typical of actinomycete genes. Six
      of these show homology to known genes: an esterase, a transposase, a peptidyl
      prolyl cis-trans isomerase, a subtilisin inhibitor-like protein, and two genes
      involved in bacterial cell wall biosynthesis. All the ORFs are transcribed toward
      the Er biosynthetic gene cluster (in the same direction as eryK). From the
      predicted functions of the putative ORF products none of these genes appear to be
      involved in the biosynthesis of Er. The eryK gene thus most likely defines one
      end of the Er biosynthetic gene cluster.

PMID- 9249069
TI  - A negative regulatory region of the murine Hox11 gene.
AB  - The HOX11 gene was isolated from the chromosomal breakpoint of human T cell acute
      lymphoblastic leukemias with a chromosomal translocation t(10;14). Expression of
      this proto-oncogene is strictly controlled in normal tissues. However, regulatory
      elements of the gene have never been studied. Since the HOX11 gene is well
      conserved between human and murine, we sequenced 5' flanking region of the murine
      Hox11 gene and analyzed the elements. We identified the transcription start site
      (+1) of the gene using mRNA from fetal spleens by primer extension analysis. The
      start site was determined at 795 bp upstream from the ATG site. A typical TATA
      box sequence was found at 35 bp upstream from the start site. Furthermore,
      promoter activity of the 5' flanking region of the start site was monitored by
      luciferase assay. The activity mainly located within a 540-bp fragment
      immediately upstream from the start site (-540 to +1). The (-1240 to -540) region
      contained a negative regulatory element of the transcription. The TATA box
      sequence and the nucleotide sequence around the transcription start site were
      conserved in the human HOX11 gene. The transcription start site of the human
      HOX11 gene in normal tissues is discussed.

PMID- 9249070
TI  - cut-1-like genes of Ascaris lumbricoides.
AB  - Three genomic fragments homologous to cut-1 of Caenorhabditis elegans (C.
      elegans) have been identified in the intestinal parasitic nematode Ascaris
      lumbricoides (A. lumbricoides). Two of these fragments identify one region of the
      A. lumbricoides genome; they are separated by 8-9 kb and have opposite
      orientation, with the direction of transcription converging toward the center of
      the region. The third gene, which has been studied more completely, is in a
      different region of the genome separated from the first one by not less than 12
      15 kb. The complete genomic sequence of this third gene has been determined. cDNA
      overlapping clones were obtained from adult A. lumbricoides RNA via the rapid
      amplification of cDNA ends (RACE) procedure [Frohman et al., 1988. Rapid
      production of full-length cDNAs from rare transcripts: amplification using a
      single gene-specific oligonucleotide primer. Proc. Natl. Acad. Sci. USA 85, 8998
      9002] and sequenced. The mature mRNA of this gene, which we have named ascut-1,
      is trans-spliced to the spliced leader sequence of nematodes (SL1) [Krause, M.,
      Hirsh, D., 1987. A trans-spliced leader sequence on actin mRNA in C. elegans.
      Cell 49, 753-761]. The mRNA is 1684 nt long plus the poly(A) tail and contains
      four exons with a 138 nt untranslated 5' leader and a 388 nt untranslated 3'
      tail. Conceptual translation of the coding sequence shows a protein of 385 aa
      with a signal peptide of 16 aa. The protein shows very high homology with CECUT
      1, the product of the C. elegans gene cut-1 and with other cuticlin proteins of
      nematodes. A 262 amino acids region which is strongly conserved between these
      proteins seems to identify a group of proteins, so far restricted to nematodes,
      for which the name CUT-1-like is proposed.

PMID- 9249071
TI  - HCF-1, a hydrophobin from the tomato pathogen Cladosporium fulvum.
AB  - A hydrophobin, named HCF-1, was isolated from the culture medium of Cladosporium
      fulvum, the causal agent of tomato leaf mould. The protein forms insoluble
      aggregates when the medium is vigorously aerated. These aggregates can be
      dissociated by trifluoroacetic acid into monomers which migrate as 10-kDa
      molecules on SDS-PAGE. HCf-1 is encoded by a single gene, HCf-1. The gene
      contains two small introns and is translated into a 105-amino acid protein which
      is then processed to give a mature 83-amino acid protein. The position of the
      eight cysteine residues and the predicted hydrophobicity profile are typical of
      fungal hydrophobins. HCf-1 RNA is expressed in growing mycelium and conidia but
      its quantity diminishes transiently after germination; its abundance does not
      change when the fungus is grown on nitrogen- or carbon-deficient medium. This is
      the first step in evaluating the role of hydrophobins in establishment of basic
      compatibility between C. fulvum and tomato.

PMID- 9249072
TI  - Replication of the R6K gamma origin in vitro: dependence on wt pi and hyperactive
      piS87N protein variant.
AB  - The pi protein of plasmid R6K is involved in control of replication. The aim of
      this study was to use an in vitro replication system dependent on an R6K-derived
      gamma origin of replication (gamma ori) to compare replication characteristics of
      wt pi and a hyperactive variant of pi protein (piS87N; Filutowicz et al., 1994b.
      Cooperative binding of initiator protein to replication origin conferred by
      single amino acid substitution. Nucleic Acids Res. 22, 4211-4215). The
      characteristics of in vitro replication from gamma ori reported in this
      investigation are as follows: (i) piS87N is considerably more active in
      comparison to wt pi. (ii) Replication proceeds through Cairns-type intermediates
      and the initiation site and directionality of the fork movement are similar in
      the presence of both proteins. (iii) Replication forks emanate unidirectionally
      in the vicinity of the cluster of seven 22-bp direct repeats within gamma ori.
      (iv) Replication dependent on wt pi, but not piS87N, is stimulated up to 1.5-fold
      by rifampicin.

PMID- 9249073
TI  - Primary structure and developmental acidic to basic transition of 13
      alternatively spliced mouse fast skeletal muscle troponin T isoforms.
AB  - Large samples of original cDNAs encoding neonatal and adult mouse fast skeletal
      muscle troponin T (fTnT) have been isolated and characterized. The results
      demonstrate expression relationships of 8 alternatively spliced exons of the fTnT
      gene and reveal the primary structure of as many as 13 fTnT isoforms that diverge
      into acidic and basic classes due to differential mRNA splicing in the N-terminal
      variable region. In the C-terminal variable region encoded by the mutually
      exclusive exons 16 and 17, the splicing pathway and structure of exon 16 appears
      to be adult fTnT-specific, suggesting an adaptation to the functional demands of
      mature fast skeletal muscle. The cloned cDNAs were expressed in E. coli as
      standards to identify a high M(r) to low M(r), acidic to basic fTnT isoform
      transition in postnatal developing skeletal muscles. Different from the
      developmental cardiac TnT switch generated by alternative splicing of a single
      exon, the fTnT isoform transition is an additive effect of alternative splicing
      of multiple N-terminal-coding exons, especially exons 4, 8 and fetal that are
      expressed at higher frequencies in the neonatal than in the adult muscle. The
      developmental fTnT isoform primary structure transition in both N- and C-terminal
      variable regions suggest a physiological importance of the apparently complex TnT
      isoform expression.

PMID- 9249074
TI  - Nucleotide sequence of the gene coding for SEC14p in Candida (torulopsis)
      glabrata.
AB  - A gene coding for SEC14p from Candida glabrata has been cloned and characterized.
      Nucleotide (nt) sequence analysis reveals an open reading frame of 909 bp and
      predicts the synthesis of a polypeptide of 302 amino acid (aa) residues.
      Comparison of nt and aa sequences shows that the gene exhibits a much higher
      homology to the Saccharomyces cerevisiae (72% and 87%, respectively) than to the
      Candida albicans (55% and 65%, respectively) SEC14 gene.

PMID- 9249075
TI  - Cloning and expression of human NF-YC.
AB  - The CCAAT box is an important element in eukaryotic promoters and NF-Y (CBF) is a
      conserved heterotrimeric protein binding to it. Two subunits, NF-YB and NF-YC,
      contain a histone-like motif. We cloned the complete cDNA coding for the human NF
      YC gene. The ORF codes for a 335 aa protein that shows virtual identity to the
      rat sequence, confirming the stunning invariance of NF-Y genes across species. We
      expressed and purified the yeast homology domain of NF-YC in bacteria and
      performed EMSA together with the corresponding conserved domains of NF-YA and NF
      YB, obtaining a CCAAT-binding mini-NF-Y. We evaluated the expression of NF-YC and
      found that mRNA levels are similar in different human tissues except in testis.

PMID- 9249077
TI  - Functional outcome after coloanal versus low colorectal anastomosis for rectal
      carcinoma.
AB  - BACKGROUND: The aim of this study was to compare retrospectively the longterm
      functional results of straight or J-pouch coloanal anastomosis and low colorectal
      anastomosis in patients operated for rectal carcinoma. STUDY DESIGN: Of the 260
      patients who underwent rectal resection for carcinoma in our department during a
      12-year period, 105 were included in this study. Of these, 37 had straight
      coloanal, 15 J-pouch coloanal, and 53 low colorectal anastomoses. RESULTS: At 1
      year of followup, continence was significantly better after low colorectal than
      straight coloanal anastomosis (perfect continence: 81% versus 51%; p < 0.01). No
      significant difference was observed for continence after J-pouch coloanal and low
      colorectal anastomosis. Stool frequency during a 24-hour period was significantly
      higher after straight coloanal anastomosis than after either J-pouch coloanal (p
      < 0.05) or low colorectal anastomosis (p < 0.01). Night stools were significantly
      more frequent after straight than J-pouch coloanal anastomosis (p < 0.05). Three
      years after surgery, continence had improved in the three groups, as 70% of the
      straight coloanal group, 91% of the J-pouch coloanal group, and 94% of the
      colorectal anastomosis group had perfect continence (p < 0.02 versus straight
      coloanal anastomosis). No significant difference for continence was observed
      between the J-pouch coloanal and low colorectal anastomosis groups. Neither were
      significant differences observed among the three groups for urgency, gas/stool
      discrimination, stool frequency (including night stools), or the need for
      medication. CONCLUSIONS: The functional results of both J-pouch coloanal and low
      stapled colorectal anastomosis seem better than those of straight coloanal
      anastomosis. Both J-pouch and low-stapled procedures can safely be proposed for
      patients with rectal carcinoma requiring total mesorectal rectal excision;
      however, because low stapled colorectal anastomosis seems to us easier and faster
      to perform, we consider it the best option for rectal reconstruction after
      proctectomy for carcinoma, provided it is possible based on the level of the
      tumor.

PMID- 9249076
TI  - Factors associated with the occurrence of leaks in stapled rectal anastomoses: a
      review of 1,014 patients.
AB  - BACKGROUND: Despite improvement in surgical techniques and stapling devices
      during the last 10 years, colorectal anastomoses are still prone to leakage. The
      purpose of this study was to assess the performance and safety of stapled
      anastomoses in rectal surgery and to identify factors that influence the
      occurrence of anastomotic leaks. STUDY DESIGN: A review was undertaken of 1,014
      patients who underwent stapled anastomoses to the rectum or anal canal for
      colorectal cancer or benign disease between 1989 and 1995 in a tertiary care
      institution. Indications for operations, comorbidities at admission, preoperative
      bowel preparation, stapler size, intraoperative events, associated surgical
      procedures, and clinical outcomes were tested for any association with
      anastomotic leak. RESULTS: A double stapled technique was used in 154 patients
      and a conventional single stapler technique was used in 860. Postoperative
      mortality was 1.6%, and the overall morbidity was 18.4%. Clinically apparent
      anastomotic leak developed in 29 patients (2.9%). Anastomotic dehiscence occurred
      in 22 of 284 patients (7.7%) after low stapling (within 7 cm from the anal verge)
      and in 7 of 730 patients (1%) after high stapling (p < 0.001). Diabetes mellitus,
      use of pelvic drainage, and duration of surgery were significantly related to the
      occurrence of anastomotic leak by the univariate analysis. Multivariate
      regression analysis identified an anastomotic distance from the anal verge within
      7 cm as the only variable related to the occurrence of postoperative leak (p <
      0.001). CONCLUSION: Low anastomoses were associated with a leak rate greater than
      with high colorectal anastomoses. We conclude that anastomoses to the rectum
      using the circular stapler can be done with low mortality and morbidity.

PMID- 9249078
TI  - Failure in resection of multiple pulmonary metastases from colorectal cancer.
AB  - BACKGROUND: To clarify whether or not multiple pulmonary metastases from
      colorectal cancer are contraindicated for a surgical resection, we
      retrospectively evaluated the influence of the number of pulmonary metastases on
      both the postthoracotomy survival and the pattern of the first failure. METHODS:
      From 1981 to 1993, 36 patients underwent a complete resection for pulmonary
      metastases from colorectal cancer. RESULTS: Of the various factors investigated
      including gender, primary site, disease-free interval, tumor size, the number of
      metastases, type of resection, and the history of hepatic metastases, only the
      number of pulmonary metastases was found to be significantly related to
      postthoracotomy survival. The rate of disease-free survival at 5 years was 62%
      for solitary metastasis (n = 17), 35% for two metastases (n = 8), and 0% for four
      or more metastases (n = 11). The pattern of failure also differed according to
      the number of pulmonary metastases. In particular, the incidence of local
      recurrence at the primary site increased with the number of pulmonary metastases
      (ie, 1 of 17 patients with a solitary metastasis, 3 of 8 with two metastases, and
      6 of 11 with four or more metastases). CONCLUSIONS: These results suggest that
      multiple metastases might indicate the presence of local recurrence at the
      primary site; therefore, in cases of multiple pulmonary metastases, the primary
      site should be thoroughly explored.

PMID- 9249079
TI  - Liver transplantation after jejunoileal bypass for morbid obesity.
AB  - BACKGROUND: Jejunoileal (JI) bypass was developed as a therapy for morbid obesity
      in the late 1960s but has since been abandoned because of a high rate of
      complications, including cirrhosis. The need for liver transplantation after JI
      bypass has been infrequent, with only four previous patients reported in the
      literature; however, because the time to develop symptomatic end-stage liver
      disease after JI bypass may be quite long (25 years or more), the incidence of
      patients who will require liver transplantation may only now be increasing. STUDY
      DESIGN: We reviewed our experience with JI bypass and liver transplantation in
      380 consecutive adult patients since 1985. RESULTS: Four patients underwent liver
      transplantation for cirrhosis after JI bypass, all within the last 48 months. The
      mean duration of time from JI bypass to transplantation was 22.3 years. All
      patients had complications, in addition to their liver disease, which were
      related to the JI bypass, which included nephrolithiasis, cholelithiasis, vitamin
      deficiencies, renal insufficiency, and d-lactic acidosis. One patient had the JI
      bypass taken down before transplantation, which precipitated acute liver and
      renal failure, necessitating urgent transplantation. One patient, who had the JI
      bypass taken down at the time of transplant, has developed recurrent morbid
      obesity, while the other three patients have not. The one patient who has not had
      the JI bypass taken down has not developed evidence of recurrent liver disease
      and is followed with monthly liver function tests and yearly biopsies.
      CONCLUSIONS: The incidence of patients who require liver transplantation after JI
      bypass may be on the increase. Take down of the JI bypass may precipitate acute
      liver failure in the cirrhotic patient. JI bypass should be accomplished either
      at the time of transplantation or if signs of liver dysfunction occur after
      transplantation. Liver transplant recipients can be at risk for recurrent obesity
      after takedown of the JI bypass. Transplantation for those patients with
      decompensated cirrhosis after JI bypass has demonstrated excellent early results.

PMID- 9249080
TI  - The surgical risk of pancreas transplantation in the cyclosporine era: an
      overview.
AB  - BACKGROUND: Pancreas transplants are still associated with the highest surgical
      complication rate of all routinely performed solid organ transplants. To date,
      the impact of serious surgical complications in the cyclosporine era on
      perioperative patient morbidity, graft and patient survival, and hospital costs
      has not been analyzed in detail. STUDY DESIGN: We retrospectively studied
      surgical complications after 445 consecutive pancreas transplants (45%
      simultaneous pancreas-kidney [SPK], 24% pancreas after kidney [PAK], and 31%
      pancreas transplant alone [PTA]). Of these, 80% were primary transplants, 20%
      were retransplants. Cadaver donors were used in 92%, living related donors in 8%.
      To develop guidelines for their prevention and management, we studied the impact
      of significant surgical complications (intra-abdominal infections, vascular graft
      thrombosis, and anastomotic leak) requiring relaparotomy on graft and patient
      survival. RESULTS: Relaparotomy was required after 32% of all pancreas
      transplants (SPK: 36%, PAK: 25%, PTA: 16% [p = 0.04]). Perioperative mortality
      was 9%. Graft and patient survival rates were significantly lower for recipients
      with (versus without) relaparotomy. The most common procedures were drainage of
      intra-abdominal abscess with graft necrosectomy (50% of all relaparotomies) and
      transplant pancreatectomy (34%). The most common causes of relaparotomy were
      intra-abdominal infection, vascular graft thrombosis, and anastomotic leak. Intra
      abdominal infection occurred in 20% (SPK: 18%, PAK: 24%, PTA: 20% [p = NS]). The
      rate was significantly higher for living related donor (42%) versus cadaver donor
      (18%) recipients and for those with enteric-drained (39%) versus bladder-drained
      (18%) transplants. Graft and patient survival rates were significantly lower for
      recipients with (versus without) intra-abdominal infection. Outcome was better
      after bacterial (versus fungal) infections. For SPK recipients, those not on
      dialysis before the transplant had significantly higher graft survival than those
      on dialysis. Vascular graft thrombosis occurred in 12% of all recipients. The
      rate was significantly higher for PAK (21%) than for PTA (10%) and SPK (9%)
      recipients. It was significantly lower for recipients of grafts with donor iliac
      Y-graft reconstruction (versus all other types of arterial reconstruction) and
      with right-sided (versus left-sided) graft placement. Of note, patient survival
      was not different for recipients with versus without vascular graft thrombosis.
      The incidence of anastomotic or duodenal stump leaks was 10%; of these
      recipients, 70% required relaparotomy. Patient and graft survival rates were no
      different for recipients with versus without leaks. CONCLUSIONS: Serious surgical
      complications occurred in 35% of pancreas recipients and had a significant impact
      on patient and graft survival. Based on multivariate risk factor analyses, we
      recommend the following: donors over 45 years and those dying of
      cerebrocardiovascular disease should not be used; recipients over 45 years and
      those with a history of cardiac disease should be considered for a kidney
      transplant alone (KTA); surgical technique for graft procurement, preparation,
      and implantation should be meticulous; right-sided implantation and arterial Y
      graft reconstruction should be performed when possible, since they had the
      highest success rates; when complications require relaparotomy, the focus must
      switch from graft salvage to life preservation; and the threshold for
      pancreatectomy should be low. Diagnosis should be timely, and treatment and
      relaparotomy expeditious. These cornerstones of success should help decrease the
      risk of surgical complications and mortality after pancreas transplants.

PMID- 9249081
TI  - Advanced breast cancer biopsy instrumentation: a critique.
AB  - BACKGROUND: Large-core biopsies or open biopsies with needle localization have
      been the mainstay of treatment for evaluating nonpalpable mammographic
      abnormalities. The newly introduced Advanced Breast Biopsy Instrumentation (ABBI)
      system combines digital stereotactic imaging with a highly developed single-use
      biopsy device to locate and remove a radiographically discovered breast lesion to
      an accuracy of 1 mm. STUDY DESIGN: We conducted a review of the first 58 cases
      involving the use of the ABBI system. This article evaluates the accuracy of
      specimen targeting, the success rate of lesion removal, the operative
      complications, the mechanical difficulties, and patient satisfaction with the
      ABBI system. RESULTS: The lesion was removed successfully in 47 of the 58 cases.
      Nine patients were eliminated in initial screening and the procedure could not be
      completed in two. Although the success rate was high, 14 of the procedures
      required conversion to "open" ABBI procedures for completion of the biopsy.
      CONCLUSIONS: The ABBI system is an alternative to open biopsy with needle
      localization or large-core biopsy for nonpalpable mammographic abnormalities.
      This technique allows complete removal of the lesion in a one-step procedure. The
      ABBI system has certain limitations and mechanical problems, at least currently,
      and offers an advantage over current diagnostic modalities in a very limited
      number of cases only.

PMID- 9249082
TI  - Laparoscopic cholecystectomy as an outpatient procedure.
AB  - BACKGROUND: Laparoscopic cholecystectomy is still done mainly on an inpatient
      basis at hospitals or on an outpatient basis at ambulatory care departments
      inside hospitals. STUDY DESIGN: We reviewed 213 cases in which outpatient
      laparoscopic cholecystectomy was done at an ambulatory surgical center not
      associated with a hospital physically or administratively. Patients were selected
      solely on the basis of medical history and physical examination results. Patients
      received general anesthesia as is typical for outpatient procedures. Narcotic use
      was minimized to prevent postoperative nausea. The procedure did not include
      intraoperative cholangiography. RESULTS: Laparoscopic cholecystectomy took 1 to 2
      hours in three quarters of patients. Rate of conversion to open cholecystectomy
      was 2.8% (6 of 213 patients). The mean recovery period was 6.6 hours, and 97% of
      patients were discharged on the same day (ie, were treated as outpatients). We
      identified no cases of retained common duct stone. Wound complications included
      mainly seroma, wound seepage, and wound infection; 18% of these complications
      were seen at trocar sites. No major complications were seen. CONCLUSIONS:
      Elective outpatient laparoscopic cholecystectomy can be done safely with low
      morbidity, high patient acceptance, and same-day discharge in > 95% of cases.

PMID- 9249083
TI  - Effect of glutamine or glucagon-insulin enriched total parenteral nutrition on
      liver and gut in 70% hepatectomized rats with colon stenosis.
AB  - BACKGROUND: Malnutrition of enterocytes is believed to facilitate the breakdown
      of the intestinal mucosal barrier, furthering a translocation of enteric bacteria
      with subsequent severe infection, which has been described after extensive
      hepatectomy. Glutamine and glucagon insulin are said to attenuate the
      malnutrition of enterocytes. To determine whether this was true, the effects on
      the remnant liver and the gut of total parenteral nutrition supplemented by
      admixtures of glutamine and/or glucagon insulin were investigated in rats
      subjected to massive hepatectomy and transient intestinal stasis. STUDY DESIGN:
      Rats underwent a permanent cannulation of the superior caval vein without
      restraining their mobility, a 70% hepatectomy, and a 24 hour string-ligation
      stenosis of the colon. A standard total parenteral nutrition solution was infused
      without or with 2% glutamine and without or with glucagon-insulin
      supplementation, respectively. RESULTS: Glutamine and glucagon-insulin
      supplemented total parenteral nutrition increased ileal mucosal DNA
      concentrations during and after intestinal stasis. Glutamine or glucagon-insulin
      alone had less pronounced effects. In the liver, the combined supplementation
      resulted in reduced adenosine triphosphate concentrations and increased
      mitochondrial adenosine triphosphate synthesis as well as in an early increase in
      DNA concentrations. CONCLUSION: Glutamine and glucagon-insulin enriched total
      parenteral nutrition attenuates malnutrition of enterocytes after massive
      abdominal stress and promotes liver regeneration after extensive hepatectomy.

PMID- 9249085
TI  - Intestinal rotation abnormalities without volvulus: the role of laparoscopy.
AB  - BACKGROUND: Intestinal rotation disorders may be discovered during investigation
      for abdominal symptoms. Two questions are raised in this setting: are the
      patient's symptoms from the rotation abnormality, and is the base of the small
      bowel mesentery so narrow that it places the patient at risk for midgut volvulus?
      Previously, laparotomy was necessary to answer these questions, and then it was
      necessary to do a Ladd procedure and appendectomy if necessary. STUDY DESIGN: We
      used laparoscopic surgery to evaluate seven patients, ages 4 days to 23 years of
      age (median age 7 years), when upper gastrointestinal series revealed intestinal
      rotation abnormalities without volvulus. RESULTS: Two patients had nonrotation.
      One had Ladd's bands across the duodenum that were divided, and the appendix was
      removed. The other had diffuse peritoneal soilage from a ruptured appendix;
      irrigation and appendectomy were performed. Three patients had duodenal
      malrotation and underwent laparoscopic Ladd procedure and appendectomy. Two
      patients had combined duodenal and cecal malrotation. One of these patients had a
      previous appendectomy for what in retrospect was primary peritonitis; malrotation
      was confirmed radiologically after the operation. She underwent a laparoscopic
      Ladd procedure 3 months later. The other patient was believed to have combined
      duodenal and cecal malrotation based on radiographic studies performed during
      workup for gastroesophageal reflux. At laparoscopy the small bowel mesentery was
      believed to have a broad enough base to prevent midgut volvulus, and an
      appendectomy was done. No patient required conversion to an open procedure. The
      sole complication was intra-abdominal abscess in the child with ruptured
      appendicitis that required prolonged hospitalization and operative abscess
      drainage. Operative times ranged from 1.25-3.25 hours (median 2 hours). Time to a
      regular diet was 1-20 days (median 2 days). Resolution of symptoms was seen in 5
      of the 7 patients, with a median followup of 15 months. CONCLUSIONS: Laparoscopy
      is an excellent technique for the evaluation and definitive management of
      patients without midgut volvulus with intestinal rotation abnormalities.

PMID- 9249084
TI  - Efficacy of amino acid infusion for improving protein metabolism after surgery: a
      prospective randomized study in patients undergoing subtotal gastrectomy.
AB  - BACKGROUND: Appropriate regimens of peripheral parenteral nutrition (PPN) have
      been proposed for the improvement of protein metabolism after surgery. When
      evaluating the efficacy of administered nutrients, it is vital to consider the
      severity of surgical stresses to avoid confounding effects of the trauma on the
      postoperative metabolism. This study was designed to evaluate protein-sparing
      regimens through PPN in patients who had undergone subtotal gastrectomy. STUDY
      DESIGN: Patients hospitalized at our institutes for gastric cancer were randomly
      divided into the following five groups and received PPN for 7 days after surgery:
      1. G group (n = 9), 200 g glucose (per day); 2. AG group (n = 10), 54 g amino
      acids + 150 g glucose; 3. AGG group (n = 9), AG + 110 g glucose; 4. AGF group (n
      = 10), AG + 40 g fat; and 5. AGL group (n = 7), 58 g amino acids + 60 g glycerol.
      Biochemical studies were done before and after surgery. RESULTS: In comparison to
      G group patients, AG group patients showed less negative cumulative nitrogen
      balances. No significant differences in cumulative nitrogen balances were
      observed between AGG, AGF, and AGL groups. Restoration of the reduced serum rapid
      turnover protein occurred earlier in the AGL group than in either the AGG or the
      AGF groups. Hyperglycemia, glucosuria, and hyperinsulinemia were prominent in the
      AGG group, and less prominent in the AGL group. Marked ketosis together with an
      increase in serum-free fatty acid levels was found in the AGL group. CONCLUSIONS:
      These results suggest that in patients who have undergone major elective surgery,
      infusion of amino acid solutions is advantageous for improving protein metabolism
      after surgery, and nonprotein energy source and intake are not essential when
      combined with amino acid solutions for improving nitrogen balance after surgery.

PMID- 9249086
TI  - Role of splenectomy in gastric cancer surgery: adverse effect of elective
      splenectomy on longterm survival.
AB  - BACKGROUND: Splenectomy, and in some cases pancreatico splenectomy, has been
      advocated by surgeons in an effort to improve clearance of metastatic nodes to
      splenic hilum (node 10) and splenic artery (node 11). Although splenectomy has
      known effects on increasing morbidity and even mortality after a variety of
      surgical maneuvers including gastrectomy, the longterm effect on survival is
      controversial. The purpose of this study is to review and analyze the effect of
      splenectomy on survival in patients having curative gastrectomy for stomach
      cancer. METHODS: We reviewed the role of splenectomy in patients having curative
      gastrectomy in a data base of stomach cancer patients that had been collected in
      1987 as part of an American College of Surgeons Patterns of Care Study. This
      analysis had involved 18,344 patients, of whom 11,252 were first diagnosed in
      1982 as part of a longterm study, and 7,092 were first diagnosed in 1987 as part
      of a shortterm study. From the two data collection periods information was
      available on 12,439 patients who received cancer directed abdominal surgery;
      21.2% of these patients received a splenectomy. Among the 3,477 patients reported
      as having a curative gastrectomy (pathologically clear margins), 26.2% received a
      splenectomy. RESULTS: The operative mortality was 9.8% with splenectomy and 8.6%
      without splenectomy. In patients having a curative gastrectomy, the 5-year
      observed survival rate was 20.9% in patients having splenectomy versus 31% in
      patients who did not receive splenectomy (p < 0.0001). Examination of differences
      in survival by stage of diagnosis showed significantly reduced survival outcomes
      among patients with stage II and III, but not for those diagnosed with stage I or
      IV disease. The pattern of recurrence was moderately different with a larger
      proportion of patients having distant metastases among the group of patients who
      had undergone splenectomy compared with the patients who had not, 29% and 15.5%,
      respectively. Whether these differences are inherent in the splenectomy or in the
      associated cofactors was not determined in this study. CONCLUSIONS: The data
      suggest elective splenectomy should generally be avoided in patients with stage
      II and III gastric cancer. In patients with resectable proximal advanced (stage
      IV) cancer or who have extension to spleen and pancreas or macroscopic nodal
      metastases to splenic hilum, splenectomy might be necessary to facilitate
      complete removal of the tumor in an effort to achieve longterm tumor control. The
      importance of surgical judgment is emphasized as the major deciding factor in
      determining the need for splenectomy in the individual cancer patient.

PMID- 9249088
TI  - Laparoscopic Janeway gastrostomy: an alternative to celiotomy for the management
      of a dislodged percutaneous gastrostomy.

PMID- 9249087
TI  - Stapled anastomotic leaks.

PMID- 9249089
TI  - Pancreaticojejunostomy-securing technique: duct-to-mucosa anastomosis by
      continuous running suture and parachuting using monofilament absorbable thread.

PMID- 9249090
TI  - Grafting of the renal artery of a transplanted kidney by transfer of the iliac
      arteries.

PMID- 9249091
TI  - Video-assisted thoracic surgery in trauma patients.

PMID- 9249092
TI  - Recurrent hepatolithiasis after primary excision of choledochal cysts.

PMID- 9249093
TI  - Surgical treatment of Borrmann type IV gastric carcinoma.

PMID- 9249094
TI  - Anesthesia & Analgesia: seventy-five years of publication.

PMID- 9249095
TI  - epsilon-Aminocaproic acid plasma levels during cardiopulmonary bypass.
AB  - epsilon-Aminocaproic acid (EACA) concentrations achieved during cardiopulmonary
      bypass (CPB) have not been previously reported. It is unknown whether plasma
      concentrations reported to inhibit fibrinolysis in vitro (130 microg/mL) are
      achieved or whether differences in these levels relate to variability in
      postoperative bleeding. EACA (total intraoperative dose 270 mg/kg) was
      administered to 27 patients undergoing cardiac reoperation. The plasma EACA
      concentration was measured by using high-pressure liquid chromatography: 1) 30
      min after initiation of drug administration (baseline); 2) 30 min (CPB + 30)
      after initiation of CPB; 3) 90 min after initiation of CPB. (CPB + 90); and 4) at
      cardiopulmonary bypass termination (end CPB). Plasma EACA concentrations
      (microg/mL, min - max, mean +/- SD) were 276-998, 593 +/- 154 at baseline; 147
      527, 302 +/- 95 at CPB + 30; 112-500, 314 +/- 100 at CPB + 90; and 84-537, 317 +/
      100 at end CPB. Twenty-four-hour postoperative thoracic drainage and allogeneic
      red blood cell transfusions were not associated with plasma levels at any time.
      Although plasma EACA concentrations greater than 130 microg/mL were consistently
      achieved, we observed a marked variability (more than sixfold) in plasma
      concentrations and bleeding outcomes despite the use of a weight-based dosing
      regimen. This variability in drug levels appears to have little relevance to
      bleeding outcomes, possibly since mean plasma levels exceeded 130 microg/mL
      during CPB, and nearly all patients (26 of 27) achieved that target level.

PMID- 9249096
TI  - Radial artery diameter decreases with increased femoral to radial arterial
      pressure gradient during cardiopulmonary bypass.
AB  - A clinically significant femoral to radial artery pressure gradient sometimes
      develops during cardiopulmonary bypass (CPB), but the mechanism responsible is
      not clear. We investigated when the pressure gradient developed and what
      mechanism could be responsible by comparing mean femoral to mean radial artery
      pressure and radial artery diameter in 75 male patients undergoing coronary
      artery bypass grafting. A pressure gradient > or =5 mm Hg (High-P) occurred in 38
      patients, and the remaining 37 patients had pressure gradients <5 mm Hg (Low-P)
      at sternal closure. In High-P group, the pressure gradient was significantly
      greater (4.8 +/- 3.1 vs 1.0 +/- 3.1 mm Hg; P < 0.001) than in Low-P group, and
      the ratio of radial artery diameter to the diameter after induction of anesthesia
      was significantly decreased (0.79 +/- 0.12 vs 0.87 +/- 0.14; P = 0.006) at 5 min
      after aortic clamping. The pressure gradient and the arterial diameter changes
      persisted until sternal closure. There was a negative linear correlation between
      the pressure gradient (deltaP) and the radial artery diameter ratio (D) at
      sternal closure (D = -15.0deltaP + 16.6, r = 0.39, P < 0.001). In a subgroup of
      11 High-P patients, palm temperature was significantly lower (P < 0.05) than that
      of 11 Low-P patients during and after CPB. We conclude that the femoral to radial
      artery pressure gradient develops by 5 min after aortic clamping during CPB and
      persists until sternal closure, and that radial artery constriction could be
      responsible for the pressure gradient. IMPLICATIONS: A femoral to radial pressure
      gradient has been observed after cardiopulmonary bypass. Arterial vasodilation
      and vasoconstriction have been considered as causes for this gradient. We
      measured radial artery diameter using pulsed Doppler ultrasound and examined
      radial artery vasodilation versus vasoconstriction as possible mechanisms for the
      pressure gradient.

PMID- 9249097
TI  - Does the platelet-activated clotting test (HemoSTATUS) predict blood loss and
      platelet dysfunction associated with cardiopulmonary bypass?
AB  - Platelet dysfunction is a major cause of bleeding after cardiopulmonary bypass
      (CPB). No timely, simple, point-of-care determinant of platelet function is
      available for clinical use. Adding platelet-activating factor to conventional
      activated clotting time methods (platelet-activated clotting test [PACT])
      (HemoSTATUS; Medtronic, Inc., Parker, CO) produces rapid results (<3 min) and may
      yield a measure of platelet responsiveness and whole blood procoagulant activity.
      Blood samples were drawn for PACT, platelet count, prothrombin time, activated
      partial thromboplastin time, and thromboelastogram (TEG) from 200 patients
      undergoing cardiac surgery. The PACT significantly decreased from the baseline to
      postprotamine time interval (P < 0.001). The PACT correlated with 4-h mediastinal
      blood loss (r = -0.30, P = 0.014). The TEG maximum amplitude also correlated with
      4-h mediastinal blood loss (r = -0.32, P = 0.003). The PACT had a sensitivity and
      specificity comparable to routine laboratory coagulation tests in predicting
      blood loss. The TEG maximum amplitude, however, was more predictive than both the
      PACT and routine coagulation tests in this respect. The PACT may be a useful
      indicator of platelet responsiveness or whole blood procoagulant activity, but we
      did not find it superior to other tests of coagulation function for predicting
      excessive blood loss after CPB.

PMID- 9249098
TI  - The effects of cross-linked hemoglobin on regional vascular conductance in dogs.
AB  - Hemoglobin (Hgb) solutions cause systemic vasoconstriction, which might limit
      their use as intraoperative blood substitutes. This constriction is thought to be
      caused by interaction between Hgb and nitric oxide (NO). To determine whether
      alpha-alpha cross-linked hemoglobin (XL-Hgb) interferes with NO-mediated
      vasodilation caused by acetylcholine (ACh) and sodium nitroprusside (NTP), we
      infused these compounds into the femoral, superior mesenteric, and circumflex
      coronary arteries of anesthetized dogs (n = 6) before and after partial exchange
      transfusion with XL-Hgb. Additional animals (n = 6) were studied after treatment
      with 5% albumin. XL-Hgb administration increased mean arterial pressure (MAP)
      from 81 +/- 5 to 112 +/- 8 (P < 0.05). Albumin reduced MAP from 84 +/- 4 mm Hg to
      76 +/- 4 mm Hg (P < 0.05). Vascular conductance after XL-Hgb decreased in the
      femoral artery, was not changed in the mesenteric bed, and increased modestly in
      the coronary artery (from 0.19 +/- 0.03 to 0.26 +/- 0.02 mL x mm Hg(-1) x min(
      1), P < 0.05). After albumin, conductance was unchanged in the femoral artery and
      increased in the mesenteric artery. Conductance also increased in the coronary
      bed (from 0.25 +/- 0.02 to 0.49 +/- 0.03 mL x mm Hg(-1) x min(-1), P < 0.05). The
      vasodilator response to ACh in the femoral or mesenteric beds was either
      unaffected or augmented by either XL-Hgb or albumin. In the coronary bed, XL-Hgb
      blunted the dilator responses to ACh and NTP, while albumin augmented the
      coronary dilator responses to ACh. In five additional dogs, the NO synthase
      inhibitor N(G)-monomethyl L-arginine caused MAP to increase from 85 +/- 4 to 90
      +/- 8 mm Hg and blunted the coronary dilator responses to ACh by approximately
      25%. Subsequent XL-Hgb administration caused a further increase in MAP to 112 +/-
      19 mm Hg (P < 0.05) and also further blunted ACh-mediated vasodilator responses
      in the coronary circulation. XL-Hgb has complex effects on the circulatory
      system, including a reduction in the vasodilator responses to ACh and NTP in
      canine coronary arteries in vivo. The potential impact of these events on
      patients with significant coexisting disease is unclear.

PMID- 9249099
TI  - The impact of prostanoids on pulmonary gas exchange during abdominal surgery with
      mesenteric traction.
AB  - We investigated the effect of intravenous (iv) ibuprofen on prostanoid release
      and on pulmonary gas exchange after abdominal mesenteric traction (MT) during
      either abdominal aortic surgery or pancreas resection. In a prospective,
      randomized, double-blind study, 400 mg ibuprofen (pancreas n = 13, aorta n = 13)
      or a placebo (pancreas n = 13, aorta n = 13) was administered iv before skin
      incision. MT was applied uniformly. The prostanoid plasma concentrations, venous
      admixture (Q(va)/Q(t)), and PaO2/FIO2 ratio were determined at baseline (before
      MT) and 5, 15, 45, and 90 min after MT. Patients who underwent aortic surgery
      were older and exhibited a lower preoperative PaO2 than those who underwent
      pancreas resection. Placebo-treated patients revealed a 30-fold peak increase in
      6-keto-prostaglandin F1alpha (stable metabolite of prostacyclin) levels after
      intentional MT during aortic as well as pancreatic operations. This response was
      accompanied by an increase in Q(va)/Q(t) (ibuprofen: pancreas 7% +/- 1%, aorta
      14% +/- 2%; placebo: pancreas 16% +/- 3%, aorta 26% +/- 3%/15 min after MT [mean
      +/- SEM, P < 0.05, placebo vs ibuprofen]), which resulted in decreased PaO2/ FIO2
      ratio only in the aortic surgery patients (ibuprofen: 310 +/- 19; placebo: 237 +/
      24 15 min after MT, [mean +/- SEM, P < 0.05]). The authors conclude that
      ibuprofen-pretreated patients demonstrated almost constant prostanoid levels
      without changes in pulmonary gas exchange after MT.

PMID- 9249100
TI  - Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion
      requirements during orthotopic liver transplantation.
AB  - Tranexamic acid (TA) is a synthetic drug that inhibits fibrinolysis. It has been
      administered to decrease the use of blood products during cardiac surgery and
      orthotopic liver transplantation when infused in larger doses. A small-dose
      infusion of aprotinin causes a reduction in fibrinolysis and blood product
      requirement during orthotopic liver transplantation without apparent risk of
      intravascular thrombosis. This prospective study was designed to investigate
      whether a small-dose infusion of TA would be equally effective in reducing
      fibrinolysis and blood product transfusions during orthotopic liver
      transplantation. A double-blind, controlled study was undertaken to compare the
      efficacy of a small-dose TA infusion with that of a placebo. Thirty-two
      consecutive patients were randomized either to the TA group (n = 16), which
      received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control
      group (n = 16), which received an identical volume of normal saline. Coagulation
      values were measured, a field rating was made by the surgeon, and a
      thromboelastogram was produced at four predetermined intervals throughout the
      case-before TA infusion was started, after portal vein ligation, 10 min after
      reperfusion, and at the end of surgery. Intraoperative transfusion requirements
      were recorded during the procedure and for the first 24 h postoperatively. A
      record was kept of any intraoperative epsilon-aminocaproic acid administered for
      uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant
      for lysis in the control group during both the anhepatic and the neohepatic
      phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group.
      Fibrin degradation products were significantly increased (>20 microg/mL) in the
      control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D
      dimers were also significantly increased (>1 mg/L) in the control group at the
      end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA
      patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were
      no other significant differences between groups. Transfusion requirements during
      surgery and for the first 24 h postoperatively did not differ significantly
      between the two groups. We conclude that the use of small-dose TA reduces
      fibrinolysis but not transfusion requirements during orthotopic liver
      transplantation.

PMID- 9249101
TI  - The effect of dopamine on hepatic blood flow in patients undergoing epidural
      anesthesia.
AB  - We studied the effect of dopamine on hepatic blood flow during epidural
      anesthesia with the infusion of hydroxyethyl starch (HES). Hepatic blood flow was
      measured noninvasively via indocyanine green (ICG) clearance (indices: K [ICG
      disappearance rate] and R15 [15-min ICG retention rate]). Group C (n = 7)
      received no epidural anesthesia, Group E (n = 14) received epidural anesthesia,
      and Group E + D (n = 7) received a dopamine infusion (5 microg x kg(-1) x min(
      1)) during epidural anesthesia. Epidural blockade extended from a median of T5
      (T4-7) to L4 (L3-5) in Group E and from T5 (T4-7) to L4 (L3-S1) in Group E + D.
      Mean arterial pressure was maintained at preanesthetic levels in Groups E and E +
      D. K decreased and R15 increased in Group E (P < 0.05). In Groups C and E + D, K
      decreased and R15 increased slightly, but not significantly. K was smaller and
      R15 greater in Group E than in Group C (P < 0.05). We conclude that hepatic blood
      flow is decreased by epidural anesthesia, despite normotension maintained by
      continuous infusion of HES, but that this decrease in flow is reversed by the
      addition of a dopamine infusion.

PMID- 9249102
TI  - Laser Doppler skin blood flow and sympathetic nervous responses to surgical
      incision during halothane and isoflurane anesthesia.
AB  - The aim of the present study was to evaluate whether a sudden decrease in skin
      blood flow measured using a laser Doppler velocimeter reflects sympathetic
      nervous response to surgical skin incision during halothane (n = 17) and
      isoflurane (n = 16) anesthesia in 33 ASA physical status I or II patients
      scheduled for laparotomy. Plasma norepinephrine concentrations in the responding
      patients who showed a sudden decrease in the skin blood flow after surgical
      incision increased significantly and continued to increase 1-10 min after skin
      incision under halothane and isoflurane anesthesia. Although plasma
      norepinephrine concentrations in the nonresponders did not increase after
      surgical incision with halothane, the concentrations increased significantly at 1
      min, but not at 3 and 10 min, after skin incision with isoflurane. The results
      indicate that the sudden decrease in laser Doppler flow reflects the sympathetic
      response to surgical incision. However, these also suggest that the factors that
      control the skin blood flow may not be simply sympathetic but may reflect other
      modulators as well. Plasma epinephrine concentration increased during skin
      incision, but the concentrations did not differ between the patients with and
      without a sudden decrease in skin blood flow. Increases in systolic blood
      pressure and rate-pressure product on skin incision were also significantly more
      in patients with skin blood flow response compared with those without the
      response. The magnitude of changes in plasma norepinephrine concentration and
      hemodynamic variables with skin incision was greater with isoflurane than with
      halothane at the same minimum alveolar anesthetic concentration level.

PMID- 9249103
TI  - Lidocaine-related increase in defibrillation threshold.

PMID- 9249104
TI  - Midazolam premedication increases sedation but does not prolong discharge times
      after brief outpatient general anesthesia for laparoscopic tubal sterilization.
AB  - Preoperatively administered midazolam may contribute to postoperative sedation
      and delayed recovery from brief outpatient general anesthesia, particularly in
      patients who receive significant postoperative opioid analgesics. We evaluated
      the effects of midazolam premedication (0.04 mg/kg) on postoperative sedation and
      recovery times after laparoscopic tubal sterilization (Falope rings) in 30
      healthy women in a randomized, double-blind, placebo-controlled study. Patients
      received midazolam or saline-placebo intravenously 10 min before anesthesia.
      General anesthesia was induced with fentanyl, propofol, and mivacurium and was
      maintained with N2O and isoflurane. Sedation was quantified before and after
      premedication and 15, 30, and 60 min after emergence from anesthesia, using the
      digit-symbol substitution (DSST) and Trieger dot (TDT) tests. Management of
      postoperative pain and nausea and discharge criteria were standardized. Groups
      were similar with respect to age, weight, and duration of surgery and anesthesia.
      Midazolam was associated with impairment of performance on the TDT and DSST after
      premedication administration and 15 (TDT and DSST) and 30 (DSST) min after
      postanesthesia care unit (PACU) arrival. There were no differences in PACU time
      and time to discharge-readiness. In conclusion, midazolam premedication augments
      postoperative sedation in this population but does not prolong recovery times.

PMID- 9249105
TI  - Lidocaine pharmacokinetics and toxicity in newborn pigs.
AB  - In newborn infants suffering from perinatal asphyxia seizures, lidocaine (LD) has
      proved to be an effective anticonvulsant. At high concentrations, however, LD can
      itself cause convulsions. The convulsive concentration of LD (LD(conv)) varies
      among species. The aim of this study was to describe LD pharmacokinetics and to
      define the LD(conv) in awake newborn pigs. Eighteen Land race newborn pigs aged
      12-60 h, weight 1.0-2.5 kg, were enrolled. LD, 2 mg/kg intravenous (IV) bolus, (n
      = 11) was given to estimate pharmacokinetic variables. Continuous LD infusion 2
      mg x kg(-1) x min(-1) IV (n = 5) and repeated bolus doses of 15 mg/kg (n = 4)
      were given until electroencephalogram-confirmed seizures appeared. After the
      bolus injection, the elimination half-life for LD was 0.87-5.44 h. Increasing
      plasma concentration (LD(pl)) during infusion resulted in sedation after 5-10 min
      and in shivering, nystagmus, neck extension, tonic-clonic seizures at LD(conv) of
      40.6 +/- 12.7 mg/L (mean +/- SD). The unbound LD(pl) at seizures was 4.4 +/- 2.4
      mg/L. Younger animals convulsed at higher LD(conv) (r2 = 0.85). LD
      pharmacokinetics in newborn pigs were found to be dose-dependent at high plasma
      concentrations. At lower plasma concentrations, LD pharmacokinetics appeared to
      be linear. The central nervous system is the primary target for the toxic effect
      of LD in awake newborn pigs. LD neurotoxicity is age-dependent, and younger pigs
      convulse at a higher LD(conv).

PMID- 9249106
TI  - Immediate 8% sevoflurane induction in children: a comparison with incremental
      sevoflurane and incremental halothane.
AB  - We compared the efficacy and tolerance of pediatric inductions with immediate 8%
      sevoflurane in 70% nitrous oxide with either incremental sevoflurane or
      incremental halothane in 70% nitrous oxide. Forty-six unpremedicated children had
      anesthesia induced by immediate 8% sevoflurane (high sevoflurane [HS]; circuit
      primed with 70% N2O and 8% sevoflurane before application of the face mask),
      gradual sevoflurane (GS; primed with 70% N2O with increments of sevoflurane), and
      gradual halothane (HAL; 70% N2O with incremental halothane). Blind video
      recordings were made, and each child's distress was rated prior to mask
      application, during mask application, and every 10 s thereafter using a
      behavioral rating scale. There were no complications. Of those subjects not quiet
      and cooperative throughout, times to complete quiet were significantly different
      (P = 0.001): HS 19.8 +/- 8 s (range 9-34); GS 52 +/- 17 s (range 8-73); HAL 43 +/
      22 s (range 13-73). Times to eye closure were also significantly different (P <
      0.001): HS 37 +/- 10 s (range 15-56); GS 70 +/- 18 s (range 35-114); HAL 81 +/-
      34 s (range 55-140). Distress scale scores showed more rapid decrement with HS
      than with GS or HAL. We conclude that 1) immediate 8% sevoflurane/N2O results in
      a significantly faster induction than GS or HAL;2) in children, HS in N2O will
      not result in a single-breath induction under the conditions of this study; 3) in
      this small group, HS was extremely well tolerated in ASA class I and II patients.

PMID- 9249107
TI  - Studies on the safety of glucose and paraben-containing neostigmine for
      intrathecal administration.
AB  - Initial toxicity testing of neostigmine for intrathecal (IT) injection was
      performed with preservative-free isobaric solution, yet currently available
      formulations contain the preservatives methyl- and propylparaben and are usually
      mixed with glucose to yield hyperbaric solutions. Since it has been proposed that
      preservatives and hyperbaricity increase the risk of neurotoxicity after IT
      injection, we examined the safety of chronically administered IT neostigmine
      containing these additives in sheep and rats. Rats receiving daily IT injections
      of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10
      microg, exhibited dose-related antinociception, tremor, and rigidity. In
      comparison to our previously published study of neostigmine injection in solution
      without glucose, rats receiving IT neostigmine with glucose displayed less
      rigidity, tremor, and salivation. Sheep receiving daily injection of glucose
      alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no
      histologic evidence of neurotoxicity, nor did they exhibit abnormalities in
      cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal
      cord histologic examination in both species revealed fibrosis and inflammation
      secondary to the catheter without evidence of neuronal damage. These studies
      support the safety of paraben- and glucose-containing IT neostigmine.

PMID- 9249108
TI  - Epinephrine increases spinal cord concentrations of [3H]-clonidine hydrochloride
      in rabbits after epidural infusion.
AB  - Epinephrine is often given with epidurally administered drugs to prolong and
      enhance analgesia, which is partly attributed to alpha-adrenergic processes. This
      investigation evaluates the effect of epinephrine on the distribution of
      epidurally administered [3H]-clonidine hydrochloride (clonidine HCl) in serum and
      in the central nervous system. After placing a lumbar epidural catheter via a
      laminectomy, rabbits were randomly assigned to receive 20 microCi of clonidine
      HCl with epinephrine (1:200,000) (n = 5) or without (control; n = 5) for 90 min.
      During the administration, which included bolus and slow infusion, blood samples
      were collected at 15-min intervals. At the end of the administration, rabbits
      were perfused with normal saline, leading to exsanguination. Brain and spinal
      cord tissues were excised for radiometric analysis. In both groups, the
      concentration of clonidine HCl was greatest in the lumbar cord. Epinephrine
      further enhanced accumulation of clonidine HCl into the lumbar cord but did not
      alter the concentration of clonidine HCl in serum, brain, cervical cord, and
      thoracic cord. We conclude that lumbar administration of epidural clonidine HCl
      leads to increased concentrations in the lumbar cord, which is further enhanced
      by epinephrine. The increased spinal cord accumulation of clonidine may be
      another mechanism by which epinephrine improves epidural analgesia.

PMID- 9249109
TI  - The effects of epidural fentanyl on hemodynamic responses during emergence from
      isoflurane anesthesia and tracheal extubation: a comparison with intravenous
      fentanyl.
AB  - To investigate the effects of epidural fentanyl infusion on hemodynamic responses
      to recovery of consciousness and tracheal extubation, we studied 50
      unpremedicated patients scheduled for abdominal hysterectomy. All patients
      underwent epidural catheterization and blind infusion of placebo and study drug.
      Patients were assigned randomly to three groups: Group I received epidural and
      intravenous (i.v.) bolus injections and infusion of saline at the rate of 0.2 mL
      x kg(-1) x h(-1); Group II received an i.v. injection of fentanyl 2 microg/kg for
      30 s followed by 25 ng x kg(-1) x min(-1), and Group III received epidural
      injection and infusion using the same administration regimen as Group II.
      Anesthesia was induced with and maintained by isoflurane alone in an air-oxygen
      mixture. The study drug was administered at the start of retroperitoneal
      suturing. Hemodynamic variables, including systolic and diastolic arterial
      pressures (SAP and DAP, respectively) and heart rate (HR), were recorded every
      minute between the start of administration of the study and 5 min after tracheal
      extubation. During emergence from anesthesia and tracheal extubation, the
      increases in SAP, DAP, and HR in Groups II and III were significantly diminished
      (P < 0.05) compared with those in Group I. Arterial pressures, but not HR, were
      attenuated more significantly in Group III than in Group II during and after
      tracheal extubation, although the plasma fentanyl concentration was significantly
      lower (P < 0.01) in Group III (0.64 +/- 0.03 ng/ mL, [mean +/- SD]) than in Group
      II (1.15 +/- 0.09 ng/mL). The incidence of coughing during and after extubation
      was also lower with Group III. Suppression of respiratory rate prior to tracheal
      extubation was similar in the two groups receiving fentanyl. These findings
      suggest that the significant reduction in arterial pressures responses to
      tracheal extubation due to epidural fentanyl infusion may arise from more
      suppression of cough reflex than i.v. fentanyl infusion, which could be provided
      by the spinal action of epidural fentanyl as well as the supraspinal action.

PMID- 9249110
TI  - Structure-affinity relationships and stereospecificity of several homologous
      series of local anesthetics for the beta2-adrenergic receptor.
AB  - Local anesthetics inhibit binding of ligands to beta2-adrenergic receptors
      (beta2ARs), and, as a consequence, inhibit intracellular cAMP production. We
      hypothesized that among homologous local anesthetics, their avidity at inhibiting
      binding of tritiated dihydroalprenolol (3H-DHA) to beta2ARs would increase with
      increasing length of alkyl substituents and would demonstrate stereospecificity.
      Specific binding of 3H-DHA to human beta2ARs was assayed in the presence of six
      different members of the 1-alkyl-2,6-pipecoloxylidide class of local anesthetics
      (including mepivacaine, ropivacaine, and bupivacaine), the R(+) and S(-)
      bupivacaine enantiomers, lidocaine, prilocaine, etidocaine, procaine, and
      tetracaine. Avidity of binding to beta2ARs increased with increasing length of
      the alkyl chain (pKi values = 2.4, 3.6, 4.3, 4.1, 4.1, 5.9 for the methyl
      [mepivacaine], ethyl, S(-)propyl [ropivacaine], butyl [bupivacaine], pentyl, and
      octyl derivatives, respectively). We found no evidence for bupivacaine
      stereospecificity (pKi values = 4.3 and 4.9 for the S(-) and R(+) isomers,
      respectively). Other amide and ester local anesthetics also showed increasing
      potency with increasing length of alkyl substituents (pKi values = 3.6, 3.8, and
      4.3 for lidocaine, prilocaine, and etidocaine; 4.2 and 5.6 for procaine and
      tetracaine, respectively). The correlation between increased inhibition of
      beta2AR binding and alkyl chain length resembles the correlation between local
      anesthetic potency at nerve block and increased alkyl chain length. The lack of
      clear stereospecificity is consistent with the relatively low potency these
      agents demonstrate at inhibition of beta2AR binding. Finally, the relatively
      potent inhibition of beta2ARs by etidocaine, tetracaine, and bupivacaine suggests
      that their propensity for cardiovascular depression after accidental intravenous
      overdose could result from beta2AR or beta1AR blockade and inhibition of cAMP
      production. IMPLICATIONS: Local anesthetics demonstrate a rank order of avidity
      for displacing ligands from beta2-adrenergic receptors such that larger molecules
      displace ligands at lower concentrations than smaller local anesthetic molecules.
      This relationship between molecular size and receptor avidity could explain the
      greater propensity for cardiovascular toxicity of relatively large local
      anesthetics such as bupivacaine.

PMID- 9249111
TI  - Ocular surface disorders in the critically ill.
AB  - Abnormalities of the cornea and conjunctiva occur in association with
      neurological diseases, nocturnal lagophthalmos, coma, infection, and mechanical
      ventilation. We investigated the incidence and causes of ocular surface disorders
      in critically ill patients. In a retrospective study, the presence of
      conjunctivitis and corneal erosion was determined by reviewing the medical charts
      of 143 mechanically ventilated patients (intensive care unit [ICU] stay > or =7
      days). In the subsequent prospective study, 15 patients who had sedatives or
      muscle relaxants administered continuously for more than 48 h in the ICU were
      investigated. Corneal erosion was examined using a slit lamp once a day. Ocular
      surface disorder was found in 28 of the 143 patients (20%) whose ICU stay
      exceeded 7 days. The incidence increased with continuous sedation (35% vs 15%).
      The incidence also increased with continuous neuromuscular blockade (39% vs 11%).
      In the prospective study, nine patients (60%) developed corneal erosion. A
      patient's inability to fully close his or her eyes increased the incidence (P <
      0.01) of corneal erosion. Protective eyelid taping was effective in preventing
      and treating the corneal erosion. In conclusion, the critically ill often develop
      ocular surface disorders, especially when sedated and immobilized. A close
      relationship was observed between these conditions and the inability to close
      one's eyes.

PMID- 9249112
TI  - The effects of halothane and isoflurane on the phosphoenergetic state of the
      liver during hemorrhagic shock in rats: an in vivo 31P nuclear magnetic resonance
      spectroscopic study.
AB  - We studied the effects of halothane versus isoflurane on the phosphoenergetic
      state and intracellular pH (pHi) of the rat liver using in vivo 31P nuclear
      magnetic resonance (NMR) spectroscopy during and after hemorrhagic shock.
      Seventeen rats were anesthetized with 1 minimum alveolar anesthetic concentration
      of halothane or isoflurane. The mean arterial blood pressure was reduced to 40 mm
      Hg and maintained at this level for 45 min by withdrawing blood from the common
      carotid artery. The shed blood was then returned slowly. In vivo 31P NMR spectra
      were consecutively collected throughout the study. The phosphoenergetic state of
      the liver was evaluated from the changes in adenosine triphosphate (ATP) and
      inorganic phosphate (P(i)) levels. pHi was calculated from the chemical shifts of
      P(i) and alpha-ATP peaks. During hemorrhagic shock, beta-ATP decreased to 35% and
      45%, and P(i) increased to 300% and 230% of their initial values in the halothane
      and isoflurane groups, respectively. Intracellular acidosis was more severe in
      the halothane group. The recoveries of beta-ATP and P(i) were better in the
      isoflurane group. Halothane showed a more detrimental effect than isoflurane on
      the hepatic phosphoenergetic level during and after hemorrhagic shock.

PMID- 9249113
TI  - Postischemic brain injury is affected stereospecifically by pentazocine in rats.
AB  - We tested whether rats treated with the sigma1-receptor ligand, (+)-pentazocine,
      during transient focal ischemia would have a smaller volume of postischemic brain
      infarction than rats treated with the nonspecific opioid-receptor ligand (-)
      pentazocine. Rats underwent focal cerebral ischemia using the filament occlusion
      technique for 2 h, followed by 22 h of reperfusion. Rats received (+) or (-)
      pentazocine (n = 9 each group) at a dose of 2 mg x kg(-1) x h(-1) by continuous
      intravenous infusion from 1 h of ischemia to 22 h of reperfusion.
      Triphenyltetrazolium-determined infarction volume of ipsilateral striatum ([+]
      pentazocine, 19 +/- 4 mm3, mean +/- SEM; [-]-pentazocine, 44 +/- 5 mm3) and
      cerebral cortex ([+]-pentazocine, 26 +/- 12 mm3; [-]-pentazocine, 134 +/- 29 mm3)
      was smaller in rats treated with (+) compared with (-)-pentazocine. Infarction
      volume in rats treated with (-)-pentazocine was also very similar to the
      infarction volume in saline-treated control rats from our previous study
      (striatum 44 +/- 4 mm3; hemisphere 136 +/- 27 mm3). These data indicate that
      sigma1-receptors may play an important role in the mechanism of injury both in
      cortex and striatum after 2 h of transient focal ischemia in rat.

PMID- 9249114
TI  - Effect of dexmedetomidine on lumbar cerebrospinal fluid pressure in humans.
AB  - Dexmedetomidine's potential for analgesia without respiratory depression and its
      opioid- and anesthetic-sparing properties make it an attractive choice as an
      anesthetic adjunct for patients undergoing neurosurgery. However, the effects of
      dexmedetomidine on intracranial pressure are not known. We therefore studied the
      effect of dexmedetomidine on lumbar cerebrospinal fluid (CSF) pressure in
      patients after transphenoidal pituitary tumor surgery. Sixteen transphenoidal
      pituitary tumor surgery patients were randomized to receive placebo (n = 9) or
      dexmedetomidine (n = 7) for 60 min in the postanesthesia care unit. The study
      drug was administered by a continuous computer-controlled infusion to achieve an
      estimated plasma dexmedetomidine concentration of 600 pg/mL, the highest plasma
      concentration that has been used for clinical purposes. Patient-controlled
      analgesia was used to administer morphine for postoperative discomfort. Lumbar
      CSF pressure (via lumbar intrathecal catheter), intraarterial blood pressure, and
      heart rate were monitored continuously. There was no change in lumbar CSF
      pressure in either group. The highest values obtained were 19 mm Hg in the
      dexmedetomidine group and 20 mm Hg in the placebo group. During infusion, mean
      arterial pressure decreased from 103 +/- 10 mm Hg to 86 +/- 6 mm Hg (P < 0.05),
      heart rate decreased from 77 +/- 12 bpm to 64 +/- 7 bpm (P < 0.05), and cerebral
      perfusion pressure decreased from 95 +/- 8 mm Hg to 78 +/- 6 mm Hg (P < 0.05) in
      the dexmedetomidine group, but not in the placebo group. We conclude that
      dexmedetomidine does not have an effect on lumbar CSF pressure in patients with
      normal intracranial pressure who have undergone transphenoidal pituitary
      hypophysectomy. IMPLICATIONS: The effects of dexmedetomidine (an alpha2-agonist)
      or placebo on lumbar cerebrospinal fluid pressure, measured via an intrathecal
      catheter, were studied postoperatively in 16 patients. Dexmedetomidine had no
      effect on lumbar cerebrospinal fluid pressure. We will continue to investigate
      the potential utility of dexmedetomidine for neurosurgical anesthesia.

PMID- 9249115
TI  - A randomized, double-blind, dose-response comparison of epidural fentanyl versus
      sufentanil analgesia after cesarean section.
AB  - This study was designed to determine and compare the dose-response
      characteristics, speed of onset, and relative potency of single-dose epidural
      fentanyl (F) and sufentanil (S) for postoperative pain relief. Eighty women
      undergoing cesarean section (C/S) with epidural 2% lidocaine with epinephrine
      (1:200,000) were randomly assigned to receive double-blind epidural
      administration of F (25, 50, 100, or 200 microg) or S (5, 10, 20, or 30 microg)
      (n = 10 per group) upon complaint of pain postoperatively. Visual analog scales
      (VAS, 0-100 mm) were used to assess pain and sedation at baseline; at 3, 6, 9,
      12, 15, 20, 25, 30, 45, and 60 min; and every 30 min until further analgesia was
      requested. The study was terminated at 30 min if satisfactory analgesia was not
      achieved. Side effects were recorded. A dose-response was demonstrated for both
      opioids. F 25 microg and S 5 microg were ineffective, with significantly fewer
      women achieving VAS scores <10 mm (P < 0.05 compared with F 100 or 200 microg and
      S 20 or 30 microg). F 100 and 200 microg and S 20 and 30 microg all achieved VAS
      scores <10 mm in all women with no differences in time to 50% reduction in VAS
      (mean 11-16 min) and no differences in duration of analgesia (mean 117-138 min).
      The 50% and 95% effective dose values for each opioid to achieve a VAS score <10
      mm were F 33 microg and 92 microg and S 6.7 microg and 17.5 microg. There were no
      differences among groups in sedation scores or side effects. Our data suggest
      that the relative analgesic potency of epidural S:F is approximately 5 and that
      there are no differences between the opioids in the onset, duration, and
      effectiveness of analgesia when equianalgesic doses are administered
      postoperatively after lidocaine anesthesia for C/S.

PMID- 9249116
TI  - The dose-response pharmacology of intrathecal sufentanil in female volunteers.
AB  - The pharmacologic effects of intrathecal sufentanil (ITS) beyond what is
      clinically administered (10 microg) are not known. We observed 18 healthy, young,
      adult female volunteers who received 12.5, 25, or 50 microg of ITS in a
      randomized, double-blind fashion for 11 h. Analgesia was assessed by pressure
      algometry at the tibia. Respiratory function was assessed by pulse oximetry,
      respiratory rate, arterial blood gas, the ventilatory response to CO2, and a
      respiratory intervention score (RIS). The incidence and severity of side effects
      also were documented. Serum sufentanil levels were measured for 4 h after ITS
      administration. We found that ITS produced statistically significant changes in
      algometry, doubling the pressure required to produce moderate pain. However,
      doses of ITS greater than 12.5 microg failed to produce proportionate increases
      in the duration or intensity of analgesia. All doses of ITS produced significant
      respiratory depression, but only the RIS was significantly related to ITS dose.
      Neither respiratory rate nor sedation reliably predicted hypoxemia. Supplemental
      oxygen by nasal cannula consistently prevented pulse oximeter readings below 90%.
      Serum sufentanil concentrations were related to ITS dose in a statistically
      significant manner, reached clinically significant concentrations, and followed a
      time course similar to analgesia and measures of respiratory depression. However,
      there was no significant increase in measured analgesia associated with the
      increases in serum sufentanil concentrations. We conclude that in our volunteer
      model of lower extremity pain, administering ITS in doses larger than 12.5 microg
      does not improve the speed of onset, magnitude, or duration of analgesia and only
      causes dose-related increases in serum sufentanil concentrations, which may
      augment respiratory depression.

PMID- 9249117
TI  - Epidural meperidine after cesarean section: the effect of diluent volume.
AB  - We investigated the effect of diluent volume on analgesia and systemic absorption
      from epidural meperidine after cesarean section in a randomized, double-blind
      study. At the first request for postoperative analgesia, 36 parturients were
      given epidural meperidine 25 mg diluted with saline to either 2 mL (12.5 mg/mL),
      5 mL (5 mg/mL), or 10 mL (2.5 mg/mL). Visual analog pain scores measured in the
      first 30 min were greater in the 2-mL group compared with both the 5-mL group (P
      = 0.028) and the 10-mL group (P = 0.031). Onset of analgesia (time for visual
      analog pain scores to decrease by 50%) was also slower in the 2-mL group (17.5
      min) compared with the 5-mL group (9 min; P = 0.015) and the 10-mL group (12 min;
      P = 0.003); there were no differences between the 5-mL group and the 10-mL group.
      Duration of analgesia and plasma concentrations of meperidine were similar among
      groups. No adverse side effects were recorded. Previous work has suggested that
      injection of epidural opioids in large volumes increases the potential risk of
      respiratory depression from cephalad spread of the drug. Therefore, we conclude
      that analgesia is optimum when epidural meperidine is administered diluted to 5
      mL.

PMID- 9249118
TI  - Safe epidural analgesia in thirty parturients with platelet counts between 69,000
      and 98,000 mm(-3).
AB  - Regional anesthesia is a popular form of pain relief for the management of labor
      and delivery. Thrombocytopenia is considered a relative contraindication to the
      administration of regional anesthesia. Some authorities have recommended that an
      epidural anesthetic be withheld if the platelet count is <100,000 mm(-3). For the
      period of March 1993 through February 1996, we reviewed the charts of all
      parturients who had a platelet count <100,000 mm(-3) during the peripartum
      period. Eighty women met this criterion. Of these 80, 30 had an epidural
      anesthetic placed when the platelet count was <100,000 mm(-3) (range 69,000
      98,000 mm(-3)), 22 had an epidural anesthetic placed with a platelet count
      >100,000 mm(-3) that subsequently decreased below 100,000 mm(-3), and 28 did not
      receive a regional anesthetic. We found no documentation of any neurologic
      complications in the medical records. We conclude that regional anesthesia should
      not necessarily be withheld when the platelet count is <100,000 mm(-3).

PMID- 9249119
TI  - Maternal and fetal effects of isoproterenol in the gravid ewe.
AB  - Detection of the intravascular placement of epidural catheters is an important
      but difficult task. In this study, we evaluated maternal and fetal hemodynamic
      responses to intravenous (i.v.) and epidural injection of isoproterenol (ISO), a
      proposed chronotropic test dose, in gravid ewes. Near-term, chronically
      instrumented, gravid ewes with single fetuses were studied at least 48 h after
      surgery. We continuously recorded maternal heart rate (MHR), systemic and
      pulmonary blood pressures, uterine blood flow (UBF), and fetal blood pressure and
      heart rate. Maternal cardiac output was measured by thermodilution. In random
      sequence, each ewe (n = 11) received i.v. injections of saline, epinephrine (EPI)
      15 microg; ISO 4, 16, and 80 microg; or epidural (n = 9 ewes) injections of
      saline, ISO 4 microg and ISO 40 microg. All variables returned to baseline
      between experiments. Sections of lumber spinal cord were harvested from five
      animals for later histopathological study. I.v. ISO caused a dose-related
      increase in MHR. Cardiac output also increased transiently after all doses of ISO
      but not after EPI. Maternal diastolic blood pressure decreased after ISO 16 and
      80 microg. UBF decreased significantly for 120 s after EPI 15 microg. Epidural
      ISO did not significantly change maternal systemic or pulmonary blood pressure,
      cardiac output, or UBF. The 40-microg dose increased MHR significantly. No
      histopathological changes were seen in three ISO-exposed and two control spinal
      cords. I.v. ISO reliably induces maternal tachycardia in nonstressed gravid ewes.
      Unlike EPI, I.v. ISO lacks a statistically significant effect on UBF. However,
      ISO seems to be rapidly absorbed from the epidural space. Identifying the source
      of maternal tachycardia after epidural injection of a large dose of ISO could be
      difficult. If the absence of histopathological change is confirmed, ISO
      represents an alternative to EPI as a chronotropic test dose.

PMID- 9249120
TI  - Ondansetron versus metoclopramide in the treatment of postoperative nausea and
      vomiting.
AB  - In this prospective, randomized, double-blind study, we compared the efficacy and
      safety of ondansetron and metoclopramide in the treatment of postoperative nausea
      and vomiting (PONV). One hundred seventy-five patients with PONV during recovery
      from anesthesia for gynecological laparoscopy were treated intravenously with
      either ondansetron 4 mg (58 patients), metoclopramide 10 mg (57 patients), or
      placebo (60 patients). Early antiemetic efficacy (abolition of vomiting within 10
      min and of nausea within 30 min from the administration of the study drugs with
      no further vomiting or nausea episodes during the first hour) was obtained in 54
      of 58 patients (93.1%) in the ondansetron group, in 38 of 57 patients (66.7%) in
      the metoclopramide group, and in 21 of 60 patients (35%) in the placebo group (P
      < 0.001). This difference was still significant when controlling for age, body
      weight, history of motion sickness, previous PONV episodes, duration of
      anesthesia, and intraoperative fentanyl consumption using a logistic model. Early
      antiemetic efficacy was inversely related to the amount of fentanyl administered
      during anesthesia, regardless of treatment. According to the Kaplan-Meier method,
      the probability of remaining PONV-free for 48 h after a successful treatment was
      0.59 (95% confidence interval 0.45-0.71) in the ondansetron group, 0.45 (0.29
      0.60) in the metoclopramide group, and 0.33 (0.15-0.53) in the placebo group (P =
      0.003). In conclusion, ondansetron 4 mg is more effective than metoclopramide 10
      mg and placebo in the treatment of established PONV.

PMID- 9249121
TI  - The effects of a nonsteroidal antiinflammatory drug (ketoprofen) on morphine
      respiratory depression: a double-blind, randomized study in volunteers.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the postoperative
      requirements for opioid analgesic medication. To determine whether NSAIDs
      potentiate the respiratory effects of opioids, we studied the effects of
      ketoprofen (K), an NSAID, on respiratory depression induced by morphine (M) in
      volunteers. After ethics committee approval, 12 healthy male volunteers received
      infusions of K (1.5 mg/kg), M (0.1 mg/ kg), and KM (1.5 mg/kg + 0.1 mg/kg) in a
      double-blind, randomized, three-treatment, three-period cross-over trial. During
      the three sessions, CO2 rebreathing challenges for ventilatory and occlusion
      pressure responses to CO2 were performed immediately before and 10, 70, 130, 190,
      and 250 min after drug infusion over 10 min. Venous blood samples for plasma drug
      concentrations were withdrawn at the same times. Comparisons were made on slopes
      of ventilatory and occlusion pressure responses to CO2. Venous blood samples
      confirmed that morphine plasma concentrations were similar when subjects had
      received morphine alone and when they had received the combination of drugs.
      Morphine alone induced a respiratory depression with a decrease in both
      ventilatory and occlusion pressure responses to CO2. Ketoprofen alone did not
      produce any respiratory effects. The combination of drugs induced a decrease in
      ventilatory responses to CO2, but intergroup comparisons showed that this was
      significantly less marked than the decrease induced by morphine alone. In
      conclusion, for similar morphine plasma concentrations, respiratory depression
      was less marked with the combination of drugs than with morphine alone.
      Therefore, ketoprofen may reduce the respiratory depression induced by morphine.

PMID- 9249122
TI  - Effect of the intensity of transcutaneous acupoint electrical stimulation on the
      postoperative analgesic requirement.
AB  - Given the inherent side effects associated with both opioid and nonopioid
      analgesic drugs, a nonpharmacologic therapy that could decrease the need for
      analgesic medication would be valuable. We designed a sham-controlled study to
      assess the effect of the intensity of transcutaneous acupoint electrical
      stimulation (TAES) on postoperative patient-controlled analgesia (PCA)
      requirement for hydromorphone (HM), the incidence of opioid-related side effects,
      and the recovery profile after lower abdominal surgery. One hundred one healthy
      consenting women undergoing lower abdominal procedures with a standardized
      general anesthetic technique were randomly assigned to one of four postoperative
      analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA +
      sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA
      of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of
      electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg
      intravenously boluses "on demand," with a minimum lockout interval of 10 min. The
      TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and
      on both sides of the surgical incision. The TAES frequency was set in the dense
      and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of
      the hand and incision alternated every 6 s. The patients in Groups II-IV were
      instructed to use TAES every 2 h for 30 min while awake. After discontinuation of
      PCA, oral pain medications were administered on demand. The postoperative PCA-HM
      requirement, pain scores, opioid-related side effects, and requirements for
      antiemetic and antipruritic medication were recorded. High-TAES decreased the HM
      requirement by 65% and reduced the duration of PCA therapy, as well as the
      incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in
      the HM requirement compared with only 23% in the "sham" TAES group. We conclude
      that high-TAES produced a significant decrease in the PCA opioid requirement and
      opioid-related side effects after low intraabdominal surgery.

PMID- 9249123
TI  - The arterial blood propofol concentration preventing movement in 50% of healthy
      women after skin incision.
AB  - To target appropriate drug concentrations and to facilitate comparisons between
      drugs, the potency of propofol must be firmly established. We therefore
      determined the arterial blood propofol concentration preventing movement in 50%
      of patients after skin incision and the ability of arterial blood pressure and
      heart rate to predict movement after incision. Fifteen healthy women scheduled
      for breast surgery were randomly assigned to computer-targeted propofol blood
      concentrations. No other drugs were administered. Fifteen minutes after starting
      the propofol infusion, a 5-cm skin incision was made. Patients were observed for
      gross purposeful movement for 1 min. Arterial blood was sampled for propofol to
      confirm steady-state blood concentrations. Arterial blood pressure and heart rate
      were measured noninvasively. Logistic regression was used to calculate the
      propofol blood concentrations and arterial blood pressures at which 50% and 95%
      of patients did not move after skin incision (CP50 and CP95, MABP50 and MABP95,
      respectively). The CP50 and CP95 values for propofol were 14.3 +/- 1.6 microg/mL
      (mean +/- SE) and 20.6 microg/mL, respectively. The MABP50 and MABP95 values were
      63 +/- 4 mm Hg and 43 mm Hg, respectively. Heart rate did not differ
      significantly in patients who moved and who did not move. Propofol blood
      concentrations required to prevent movement in most patients resulted in
      significant arterial hypotension.

PMID- 9249124
TI  - Staphylococcus aureus bloodstream infections among patients undergoing
      electroconvulsive therapy traced to breaks in infection control and possible
      extrinsic contamination by propofol.
AB  - Infectious complications associated with electroconvulsive therapy (ECT) are
      extremely unusual. When five of nine patients undergoing ECT at one facility on
      June 20, 1996 developed Staphylococcus aureus bloodstream infection (BSI), an
      investigation was initiated. A retrospective cohort study, a procedure review,
      and observational and microbiologic studies were performed. A case was defined as
      any patient who had ECT at Facility A from June 1, 1995 through June 20, 1996 and
      developed S. aureus BSI <30 days after ECT. The post-ECT S. aureus BSI rate was
      significantly greater on the epidemic day than the pre-epidemic period, (i.e.,
      June 1, 1995 through June 19, 1996) (5 of 9 vs 0 of 54 patients, P < 0.001). All
      patients during the study period received propofol before ECT. Case patients were
      more likely than noncase patients to have higher maximum temperature after ECT
      (median 103.9 degrees F vs 100.0 degrees F, P < 0.03) and a greater time from
      preparation of intravenous medications to infusion (median 2.1 vs 1.1 h, P =
      0.01). All case-patient S. aureus isolates were indistinguishable by pulsed field
      gel electrophoresis. Our investigation suggests that the ECT-associated S. aureus
      BSIs were associated with infection control breaks, which possibly led to the
      extrinsic contamination of propofol. Prevention of propofol-associated infectious
      complications requires aseptic preparation and use immediately before infusion.

PMID- 9249125
TI  - The effects of sevoflurane on population spikes in CA1 and dentate gyrus of the
      rat hippocampus in vitro.
AB  - We studied the effects of sevoflurane on population spikes (PSs) in two synaptic
      pathways in rat hippocampal slices. Stimulating electrodes were placed on
      Schaffer collateral fibers or perforant path to activate inputs to CA1 pyramidal
      neurons or dentate gyrus (DG) neurons, respectively. Extracellular glass
      microelectrodes were used to record PSs. The paired-pulse stimulus was used to
      induce the paired-pulse facilitation (PPF). Sevoflurane (0.4-5.0 vol%)
      significantly decreased the amplitudes of PSs of CA1 and DG in a dose-dependent
      and reversible manner (25% effective dose values were 4.1 and 0.9 vol%,
      respectively). The stimulus-response relationships for PS amplitudes revealed
      that sevoflurane increased the threshold for PS generation in CA1 and DG.
      Sevoflurane (2.0 vol%) significantly enhanced PPF from 127% and 263% to 153% and
      494% in CA1 and DG, respectively. The results imply that the effects of
      sevoflurane on PSs are greater in DG than in CA1 neurons, that sevoflurane
      enhances the PPF in both CA1 and DG, and that the actions of sevoflurane are not
      similar to those of other volatile or intravenous anesthetics previously reported
      in hippocampal preparations. IMPLICATIONS: The volatile anesthetic sevoflurane
      alters neural excitability of individual pathways in the hippocampus in a manner
      different from other general anesthetics. The results are consistent with a site
      specific mechanism of action for general anesthesia.

PMID- 9249126
TI  - The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus
      and tibialis muscles of the rat.
AB  - Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia,
      but it is not clear how its chronic use might affect response to nondepolarizing
      muscle relaxants. We determined the magnitude and time course of the effects of
      chronic oral THA and of intravenous (IV) THA on d-tubocurarine (dTC) blockade at
      the soleus and tibialis muscles. Six groups of adult rats were given 10 mg/kg THA
      twice daily by gavage for 1, 2, 4, or 8 wk (chronic THA groups), or 1 mL of
      saline twice daily by gavage for 1-8 wk (control), or IV THA approximately 20 min
      before (acute), and the cumulative dose-response curves of dTC at the tibialis
      and soleus muscles were determined during indirect train-of-four stimulation in
      the anesthetized, mechanically ventilated rat. The 50% effective dose (ED50) and
      95% effective dose (ED95) of dTC in control rats were (mean +/- SD) 30 +/- 10 and
      61 +/- 18 microg/kg in the tibialis and 32 +/- 8 and 75 +/- 19 microg/kg in the
      soleus; respectively. IV THA increased the ED95 of dTC 2.5- to 3-fold (P < 0.05)
      but did not alter the ED50. Chronic THA increased both the ED50 and ED95 of dTC
      1.5- to 2-fold (P > or = 0.05), and this effect tended to decrease with duration
      of THA therapy. We conclude that chronic THA therapy in rats causes resistance to
      dTC, with a tendency for the resistance to decrease with time, probably because
      of down-regulation of postsynaptic acetylcholine receptors. The same may apply to
      Alzheimer's patients taking THA chronically.

PMID- 9249127
TI  - The effect of ephedrine on the onset time of rocuronium.

PMID- 9249128
TI  - Fat embolism in orthopedic surgery: role of bone marrow fatty acid.

PMID- 9249129
TI  - Occupational transmission of tuberculosis: implications for anesthesiologists.

PMID- 9249130
TI  - Three sudden postoperative respiratory arrests associated with epidural opioids
      in patients with sleep apnea.

PMID- 9249131
TI  - A case of suspected malignant hyperthermia during desflurane administration.

PMID- 9249132
TI  - Arytenoid dislocation and the laryngeal mask airway.

PMID- 9249133
TI  - Postoperative epidural fentanyl analgesia.

PMID- 9249134
TI  - An aid to learning to use the fiberoptic bronchoscope for intubation.

PMID- 9249135
TI  - Patient-controlled intranasal analgesia.

PMID- 9249136
TI  - Analysis of a straight-line capnographic waveform.

PMID- 9249137
TI  - Thoracic epidural anesthesia reduces the severity of myocardial ischemia in
      conscious dogs.

PMID- 9249138
TI  - MUC7 gene expression and genetic polymorphism.
AB  - This study examined differential expression of several mucin genes in the human
      submandibular gland and trachea, MUC7 tissue and species specificity, and MUC7
      genetic polymorphism. Mucin gene expression examined by RT-PCR indicated that
      MUC1, MUC4 and MUC7 are expressed in the human submandibular gland, while MUC1,
      MUC2, MUC4, MUC5 and MUC7 are expressed in the human trachea. Northern blot
      analysis confirmed the expression of MUC7 in the human trachea and MUC4 in the
      human submandibular gland. Northern blot analysis also demonstrated that MUC7 is
      not expressed in the submandibular/sublingual gland complexes of hamster, mouse
      and rat. Southern blot analysis suggested the presence of a MUC7 homologue in
      monkey genomic DNA. Genetic polymorphism studies of MUC7 by PCR and Southern blot
      analysis revealed the presence of a limited variable number of tandem repeats
      (VNTR) polymorphism.

PMID- 9249140
TI  - Synthesis of the dodecasaccharide fragment representing the O-polysaccharide of
      Vibrio cholerae O:1, serotype Ogawa, bearing an aglycon offering flexibility for
      chemical linking to proteins.
AB  - Two azidohexasaccharide building blocks, of which the glycosyl acceptor was the 5
      (methoxycarbonyl)pentyl glycoside, were coupled using the trichloroacetimidate
      technology. The 12 azido functions present in the dodecasaccharide thus formed
      were then converted to amino groups using hydrogen sulfide as a reducing reagent.
      Subsequent N-acylation with 4-O-benzyl-L-glycero-tetronic acid, followed by
      catalytic debenzylation yielded the desired spacer-equipped, title
      dodecasaccharide.

PMID- 9249139
TI  - Lack of acidic fibroblast growth factor activation by heparan sulfate species
      from diabetic rat skin.
AB  - The glucosaminoglycans isolated from the skin of control and streptozotocin
      diabetic rats were fractionated on ion-exchange chromatography into a heparan
      sulfate (HS)-like and a heparin-like species. In addition, a low sulfated
      fraction was isolated from the diabetics. The HS and heparin-like fractions
      isolated from the diabetics (in contrast to the low sulfated fractions) retained
      high affinity for the acidic (FGF-1) and basic (FGF-2) fibroblast growth factors.
      In culture, the fractions purified from the control rats and the heparin-like
      material isolated from the diabetics mediated the biological activity of both
      FGFs in a dose-dependent manner. By contrast, the diabetic HS-like fractions
      promoted the biological activity of FGF-2 but not of FGF-1. The results support
      the idea that the structural motives in HS required for FGF-1 and FGF-2 mediated
      receptor signalling are different. They may be relevant to the impaired wound
      healing observed in the disease.

PMID- 9249141
TI  - Changes in the secretion and glycosylation of fibronectin by human skin
      fibroblasts associated with tuberous sclerosis.
AB  - Fibroblasts from skin and skin lesions of patients with tuberous sclerosis (TS)
      and from skin of normal individuals were grown in culture. ELISA showed that the
      spent medium of those derived from TS skin lesions contained significantly more
      fibronectin (FN) than spent medium from the other cells. Amino acid compositional
      analysis of the FN from TS and normal sources revealed no substantial
      differences. However the FN of fibroblasts from TS-skin lesions was shown by
      HPAEC to contain a two- to three-fold increased content of carbohydrate. The
      changed monosaccharide composition was consistent with an increased content of N-
      and O-linked glycans and with the former containing polylactosamine chains.
      Fibroblasts from a normal individual were shown to proliferate more slowly and to
      produce larger cells when grown on FN from a TS skin lesion compared to growth on
      FN from normal skin.

PMID- 9249142
TI  - Isolation, characterization and molecular cloning of the bark lectins from
      Maackia amurensis.
AB  - A detailed study was made of the bark lectins of the legume tree Maackia
      amurensis using a combination of protein purification and cDNA cloning. The
      lectins, which are the most abundant bark proteins, are a complex mixture of
      isoforms composed of two types of subunits of 32 and 37 kDa, respectively.
      Isolation and characterization of the homotetrameric isoforms indicated that the
      32 kDa subunit exhibits a 100-fold stronger haemagglutinating activity than the
      37 kDa subunit. Molecular cloning confirmed that the two lectin subunits are
      encoded by different genes. The 32 kDa subunit is apparently encoded by a single
      gene, whereas two highly homologous genes encode the 37 kDa subunit. A comparison
      of the deduced amino acid sequences of the bark lectin cDNAs and the previously
      described cDNA encoding the seed haemagglutinin demonstrated that they are
      encoded by different genes.

PMID- 9249143
TI  - Do synovial fluid acute phase proteins from patients with rheumatoid arthritis
      originate from serum?
AB  - This study was performed in order to gain insight into the occurrence,
      glycosylation and the possible origin of the acute-phase proteins alpha1-acid
      glycoprotein (AGP) and alpha1-protease inhibitor (PI) in sera and synovial fluid
      from patients with rheumatoid arthritis (RA). Therefore paired sera and synovial
      fluid samples from patients with RA, and paired synovial fluid samples from right
      and left knees of patients with varying degrees of arthritis were studied.
      Crossed affinity immunoelectrophoresis (CAIE) was used with concanavalin A and
      Aleuria aurantia lectin for the detection of the degree of branching and
      fucosylation, respectively, and the monoclonal CSLEX-1 for the detection of
      Sialyl Lewis(X) (SLe(X)) groups on AGP. For PI, not only CAIE, but also high
      pressure-anion-exchange chromatography with pulsed amperometric detection was
      used to study the glycosylation. It was established that the concentrations of
      AGP and PI were increased in the serum of RA patients compared to normal healthy
      controls, but that the concentration of both proteins, as well as albumin, was
      significantly lower in synovial fluid than in serum. Furthermore, the type of
      glycosylation of both AGP and PI found in RA was significantly different from
      that found in normals, with increased fucosylation, but there were no major
      differences in the degree of branching of AGP- or PI-glycans in RA, compared to
      normals. No differences in glycosylation could be established between serum and
      synovial fluid in RA. For PI an increased fucosylation was found, both in serum
      and synovial fluid, using both methods of detection, and it could be established
      that only the alpha1-->3- and not the alpha1-->6-fucosylation of PI was affected
      by RA. The increased fucosylation of AGP resulted in an increased expression of
      SLe(X) on AGP-glycans. Since the alpha1-->3-fucosylation of AGP was significantly
      increased in both serum and synovial fluid from RA patients, and this correlated
      with systemic but not with local disease parameters, it can be suggested that
      acute phase proteins in synovial fluid are most probably of hepatic origin.

PMID- 9249144
TI  - Recognition of glycoconjugates by Helicobacter pylori. Comparison of two sialic
      acid-dependent specificities based on haemagglutination and binding to human
      erythrocyte glycoconjugates.
AB  - Helicobacter pylori expresses separate binding characteristics depending on
      growth conditions, as documented by binding to human erythrocyte glycoconjugates.
      Cells grown in Ham's F12 liquid medium exhibited a selective sialic acid
      dependent binding to polyglycosylceramides, PGCs (Miller-Podraza et al.(1996)
      Glycoconjugate J13:453-60). There was no binding to traditional sialylated
      glycoconjugates like shorter-chain gangliosides, glycophorin or fetuin. However,
      cells grown on Brucella agar bound both to PGCs and other sialylated
      glycoconjugates. Fetuin was an effective inhibitor of haemagglutination caused by
      agar-grown cells, but had no or a very weak inhibitory effect on
      haemagglutination by F12-grown bacteria. PGCs were strong inhibitors in both
      cases, while asialofetuin was completely ineffective. The results indicate that
      H. pylori is able to express two separate sialic acid-dependent specificities,
      one represented by binding to fetuin, as described before, and another
      represented by a selective binding to PGCs.

PMID- 9249145
TI  - Saccharide anions as inhibitors of the malaria parasite.
AB  - The asexual erythrocytic stage of Plasmodium falciparum was grown in culture in
      the presence or absence of glycoconjugate polyanions of varying structure, size
      and substitutions. Heparin, dextran sulfate, fucoidan and pentosan polysulfate
      had antimalarial IC50 values between one and 11 microg ml(-1). Constituent
      heparin disaccharides were ineffective against the malaria parasite and
      desulfation from either the O- or N-substitution sites of heparin or reduction of
      the uronic acid carboxyl group neutralized the antimalarial response to varying
      degrees. Immobilization of heparin onto agarose beads still permitted
      antimalarial activity suggesting that parasite uptake of the glycoconjugate is
      not required for inhibition. Accordingly, it is concluded that invasion of free
      parasites into the erythrocytes was inhibited rather than parasite maturation
      within the red cell. Merozoite surface antigen-1 was apparently prevented from
      binding to human erythrocytes in the presence of highly sulfated polyanions and,
      in a dose-dependent fashion, heparin.

PMID- 9249147
TI  - Glycosylation of polyclonal and paraprotein IgG in multiple myeloma.
AB  - It has previously been shown that in multiple myeloma (MM) each IgG paraprotein
      exhibits a unique oligosaccharide profile. It has been assumed that this results
      from a clone specific glycosylation machinery. However, the abnormal
      physiological environment of the bone marrow in this disease may also affect
      normal plasma cells producing polyclonal IgG. We present data to show that this
      is so and that, in two cases, the oligosaccharide profile of the polyclonal IgG
      reflected that of the paraprotein from the same patient rather than that of
      normal polyclonal IgG.

PMID- 9249146
TI  - Glycosylation of alpha1-acid glycoprotein in inflammatory disease: analysis by
      high-pH anion-exchange chromatography and concanavalin A crossed affinity
      immunoelectrophoresis.
AB  - High-pH anion-exchange chromatography with pulsed amperometric detection is a
      highly sensitive technique that can be used for detecting changes in sialylation
      and fucosylation, as well as different branching patterns of N-linked
      oligosaccharides in glycoproteins. We examined the N-glycans of alpha1-acid
      glycoprotein obtained from twelve patients with various inflammatory conditions
      with this technique, as well as traditional concanavalin A crossed affinity
      immunoelectrophoresis. We found the chromatographic profiles of N-glycans in all
      patients with rheumatoid arthritis to be very similar, but significantly
      different from normal controls. N-glycans from patients with ulcerative colitis
      also showed specific alterations in their chromatographic profiles. However, some
      heterogeneity was found between these patients, perhaps reflecting changes in
      glycosylation secondary to certain states of the disease, or to medical
      treatment. We conclude that this technique is useful for detailed mapping of
      glycosylation changes in alpha1-acid glycoprotein in clinical samples, and that
      it may be used to further increase our knowledge about glycosylation changes in
      response to inflammatory disease.

PMID- 9249148
TI  - A lectin method for investigating the glycosylation of nanogram amounts of
      purified glycoprotein.
AB  - To unravel the complexities of the glycosylation of a protein is a substantial
      task, which requires considerable effort and resources. However, in many
      situations this is unnecessary, because only a limited amount of information is
      required. A new lectin-binding assay is described which is rapid, cheap and
      versatile. A purified glycoprotein is absorbed on to the plastic surface of a
      microtitre plate. After removing unbound protein by washing, uncoated sites on
      the plate are blocked and digoxigenin or biotin-labelled lectin is added. The
      degree of lectin binding is measured using either an anti-DIG antibody or
      streptavidin conjugated enzyme, which is subsequently used to develop a colour
      reaction. Using this method it is possible to screen multiple specimens with high
      sensitivity and excellent precision. In addition, very small amounts of lectin
      are used, background absorbances are low, and the procedure does not require a
      high degree of technical skill. Because very small amounts of glycoprotein are
      needed, a glycoprotein can often be rapidly purified by batch affinity
      chromatography. The method has been successfully applied to several purified
      proteins using the lectins, Con A, LCA, LTA, MAA, and SNA, and the information
      obtained agrees with that produced by more sophisticated approaches, eg Dionex
      Carbohydrate Analyser. Using a panel of lectins, a carbohydrate structural
      profile is quickly built-up, and subtle differences in glycosylation identified.
      This method should be particularly useful for screening glycosylation in multiple
      clinical specimens; in specimens where very small amounts of material are
      available, such as membrane molecules; and in the screening of recombinant
      proteins produced commercially.

PMID- 9249149
TI  - A new entry to glycosylamines.
AB  - A new procedure for the introduction of a nitrogen atom into the anomeric centre
      leading to glycosylamines is described. The new reaction consisting of the
      condensation of a furanose with a hydroxylamine in the presence of a Lewis acid
      occurs with a complete degree of diastereoselectivity.

PMID- 9249150
TI  - Beyond CHELP: improved potential derived charges for sugars.
AB  - The partitioning of the overall molecular charge distribution into atom centered
      monopole charges, while quantum mechanically ill-defined, is nevertheless a
      technique which finds applications in several broad classes of chemical problems.
      Charges derived from fits to electrostatic potentials have an intuitive appeal
      since, in principle, these could be derived from either theoretical or
      experimental data. It has been noted, however, that such potential derived
      charges can be conformationally dependent in ways that do not appear to reflect
      the changes in the molecular wavefunction. Both the algorithm used for selecting
      points at which the molecular electrostatic potential will be fit and the density
      of points used in the fit have been suggested to influence the resultant charges.
      Recently [Stouch TR, Williams DE (1992) J Comp Chem 13: 622-32; Stouch TR,
      Williams DE (1993) J Comp Chem 14: 858-66] it has been noted that numerical
      difficulties may make it impossible to fit all the atomic charges in a molecule.
      Singular value decomposition (SVD) of the linear least squares matrices used in
      fitting atom based monopoles to molecular electrostatic potentials provides a
      tool for evaluating the integrity of the calculated charges. Based on the SVD
      analysis for a selected group of molecules we have noted particularly that
      increasing the molecular size reduces the fraction of charges which can be
      validly assigned. Users of PD derived charges, especially those who are using
      those charges for tasks other than reproduction of the MEP, should be aware that
      there is a high probability that a significant portion of those charges are
      statistically unreliable. Therefore, charges in many biological molecules, such
      as sugars, prove to be difficult to obtain by potential derived (PD) methods such
      as CHELP or CHELPG. Results from the SVD can be used to both assess PD charges
      and to generate an improved, albeit incomplete, set. Improved PD fits are
      presented for a series of simple saccharides.

PMID- 9249151
TI  - Polysaccharide components from the scape of Musa paradisiaca: main structural
      features of water-soluble polysaccharide component.
AB  - Polysaccharide components present in the pseudo-stem (scape) of M. paradisiaca
      were purified from acetone powder of the scape by delignification followed by
      extraction with aqueous solvents into water soluble polysaccharide (WSP), EDTA
      soluble polysaccharide (EDTA-SP), alkali-soluble polysaccharide (ASP) and alkali
      insoluble polysaccharide (AISP) fractions. Sugar compositional analysis showed
      that WSP and EDTA-SP contained only D-Glc whereas ASP contained D-Glc, L-Ara and
      D-Xyl in approximately 1:1:10 ratio, respectively, and AISP contained D-Glc, L
      Ara and D-Xyl in approximately 10:1:2 ratio, respectively. WSP was further
      purified by complexation with iso-amylalcohol and characterized by specific
      rotation, IR spectroscopy, Iodine affinity, ferricyanide number, blue value,
      hydrolysis with alpha-amylase and glucoamylase, and methylation linkage analysis,
      and shown to be a amylopectin type alpha-D-glucan.

PMID- 9249152
TI  - Effect of monomer composition on proton dissociation of weak polyacids.
AB  - The study of the proton dissociation process of weak polyacids (eg a carboxylic
      poly(monoprotic)acid) is based on the knowledge of the change in electrostatic
      free energy, G(el), as a function of the variation of the number of charges on
      the polymer chain. The original treatment proposed by Manning can be used to
      describe the proton dissociation process of weak poly(monoprotic)acids, in the
      absence of pH-induced conformational transitions. In order to describe the alpha
      dependence of pKa of weak co-poly(monoprotic)acids containing two different
      acidic groups in different amounts along the polymer chain, a simple modification
      of the model is proposed.

PMID- 9249153
TI  - Synthesis of glycosides in which the aglycon is an N-(hydroxymethyl)amino-1,3,5
      triazine derivative.
AB  - The synthesis of analogues of the anti-tumour drug 2-[N
      (hydroxymethyl)methylamino]-4,6-bis(dimethylamino)-1,3,5-triazine (HMPMM) in
      which the OH or a dimethylamino group is replaced by a carbohydrate has been
      explored. Triazinyl beta-glycosides were readily prepared by reaction of sugars
      with trimethyl-triazinylammonium salts. These were made with one or two
      methylamino groups on the triazine for reaction with formaldehyde to give the
      cytotoxic NMeCH2OH group. However, reaction of the triazinyl glycosides with
      formaldehyde gave complex intractable mixtures. When the carbohydrate portion was
      changed to the fully protected 2,3,4,6-tetra-O-acetyl glucose a good yield of the
      2-[N-(hydroxymethyl)methylamino]-4-(dimethylamino)-1,3,5-triazin-2 -yl tetra-O
      acetyl beta-glucoside was obtained. However, de-acetylation using sodium
      methoxide also removed the N-CH2OH group. We are investigating protection of the
      base-sensitive N-CH2OH group as trialkylsilyl and benzyl ethers and are looking
      at de-acetylation methods that are more selective. We have prepared glycosides in
      which the sugar is joined through the oxygen of the NMeCH2OH group. Coupling of
      acetobromoglucose with HMPMM catalysed by silver salts was not successful.
      Although methyl and cyclohexyl derivatives of HMPMM may be produced in high
      yields by reaction of HMPMM with methyl and cyclohexyl alcohols under acidic
      catalysis, production of glycosides in this way gave poor yields. MNDO
      calculations on reactions of HMPMM helped us devise improved reaction conditions
      for the condensation of 2,3,4,6-tetra-O-acetyl glucose with HMPMM and its
      derivatives. The best procedure to generate one of the target glycosides is to
      react 2,3,4,6-tetra-O-acetyl glucose and formaldehyde with 2-methylamino-4,6
      bis(dimethylamino)-1,3,5-triazine. The beta-glycoside product was de-acetylated
      using potassium carbonate in dry methanol.

PMID- 9249154
TI  - Computational studies of sialyllactones: methods and uses.
AB  - N-Acetylneuraminic acid (1) is a common sugar in many biological recognition
      processes. Neuraminidase enzymes recognize and cleave terminal sialic acids from
      cell surfaces. Viral entry into host cells requires neuraminidase activity, thus
      inhibition of neuraminidase is a useful strategy for development of drugs for
      viral infections. A recent crystal structure for influenza viral neuraminidase
      with sialic acid bound shows that the sialic acid is in a boat conformation [Prot
      Struct Funct Genet 14: 327 (1992)]. Our studies seek to determine if structural
      pre-organization can be achieved through the use of sialyllactones. Determination
      of whether siallylactones are pre-organized in a binding conformation requires
      conformational analysis. Our inability to find a systematic study comparing the
      results obtained by various computational methods for carbohydrate modeling led
      us to compare two different conformational analysis techniques, four different
      force fields, and three different solvent models. The computational models were
      compared based on their ability to reproduce experimental coupling constants for
      sialic acid, sialyl-1,4-lactone, and sialyl-1,7-lactone derivatives. This study
      has shown that the MM3 forcefield using the implicit solvent model for water
      implemented in Macromodel best reproduces the experimental coupling constants.
      The low-energy conformations generated by this combination of computational
      methods are pre-organized toward conformations which fit well into the active
      site of neuraminidase.

PMID- 9249155
TI  - Carbohydrate-protein interaction studies by laser photo CIDNP NMR methods.
AB  - The side chains of tyrosine, tryptophan and histidine are able to produce CIDNP
      (Chemically Induced Dynamic Nuclear Polarization) signals after laser irradiation
      in the presence of a suitable radical pair-generating dye. Elicitation of such a
      response in proteins implies surface accessibility of the respective groups to
      the light-absorbing dye. In principle, this technique allows the monitoring of
      the effect of ligand binding to a receptor and of site-directed mutagenesis on
      conformational aspects of any protein if CIDNP-reactive amino acids are involved.
      The application of this method in glycosciences can provide insights into the
      protein-carbohydrate interaction process, as illustrated in this initial model
      study for several N-acetyl-glucosamine-binding lectins of increasing structural
      complexity as well as for a wild type bacterial sialidase and its mutants.
      Experimentally, the shape and intensity of CIDNP signals are determined in the
      absence and in the presence of specific glycoligands. When the carbohydrate is
      bound, CIDNP signals of side chain protons of tyrosine, tryptophan or histidine
      residues can be broadened and of reduced intensity. This is the case for hevein,
      pseudo-hevein, the four hevein domains-containing lectin wheat germ agglutinin
      (WGA) and the cloned B-domain of WGA 1 (domB) representing one hevein domain.
      This response indicates either a spatial protection by the ligand or a ligand
      induced positioning of formerly surface-exposed side chains into the protein's
      interior part, thereby precluding interaction with the photo-activated dye. Some
      signals of protons from the reactive side chains can even disappear when the
      lectin-ligand complexes are monitored. The ligand binding, however, can
      apparently also induce a conformational change in a related lectin that causes
      the appearance of a new signal, as seen for Urtica dioica agglutinin (UDA) which
      consists of two hevein domains. Additionally, the three CIDNP-reactive amino
      acids are used as sensors for the detection of conformational changes caused by
      pH variations or by deliberate amino acid exchanges, as determined for the
      isolectins hevein and pseudo-hevein as well as for the cloned small sialidase of
      Clostridium perfringens and two of its mutants. Therefore, CIDNP has proven to be
      an excellent tool for protein-carbohydrate binding studies and can be established
      in glycosciences as a third biophysical method beside X-ray-crystallography and
      high-resolution multidimensional NMR studies which provides reliable information
      of certain structural aspects of carbohydrate-binding proteins in solution.

PMID- 9249156
TI  - Chitosan functional properties.
AB  - Chitosan is a partially deacetylated polymer of N-acetyl glucosamine. It is
      essentially a natural, water-soluble, derivative of cellulose with unique
      properties. Chitosan is usually prepared from chitin (2 acetamido-2-deoxy beta
      1,4-D-glucan) and chitin has been found in a wide range of natural sources
      (crustaceans, fungi, insects, annelids, molluscs, coelenterata etc.) However
      chitosan is only manufactured from crustaceans (crab and crayfish) primarily
      because a large amount of the crustacean exoskeleton is available as a by product
      of food processing. Squid pens (a waste byproduct of New Zealand squid
      processing) are a novel, renewable source of chitin and chitosan. Squid pens are
      currently regarded as waste and so the raw material is relatively cheap. This
      study was intended to assess the functional properties of squid pen chitosan.
      Chitosan was extracted from squid pens and assessed for composition, rheology,
      flocculation, film formation and antimicrobial properties. Crustacean chitosans
      were also assessed for comparison. Squid chitosan was colourless, had a low ash
      content and had significantly improved thickening and suspending properties. The
      flocculation capacity of squid chitosan was low in comparison with the crustacean
      sourced chitosans. However it should be possible to increase the flocculation
      capacity of squid pen chitosan by decreasing the degree of acetylation. Films
      made with squid chitosan were more elastic than crustacean chitosan with improved
      functional properties. This high quality chitosan could prove particularly
      suitable for medical/analytical applications.

PMID- 9249157
TI  - First Australasian Conference on the Chemistry and Biochemistry of Sialic Acid
      recognizing Proteins, Victorian College of Pharmacy, Monash University,
      Melbourne, Australia, 30 September-4 October, 1996.

PMID- 9249158
TI  - 6th International Congress on Cell Biology and 36th American Society for Cell
      Biology annual meeting, San Francisco, CA.

PMID- 9249159
TI  - Detection and differentiation of primate alpha-herpesviruses by PCR.
AB  - A rapid method for detection and differentiation of 5 primate alpha-herpesviruses
      (human herpes simplex virus types 1 and 2 [HSV1, HSV2], green monkey simian agent
      8, baboon herpesvirus 2 [HVP2], and macaque B virus [BV]) was developed utilizing
      the polymerase chain reaction (PCR). PCR primers were located in conserved
      regions of the gene encoding the glycoprotein B, which flanks an intervening
      region that is highly divergent among the 5 viruses. Amplified PCR products from
      the 5 viruses were readily differentiated by their unique restriction enzyme
      digestion patterns. No variation in digestion patterns was noted among strains of
      HSV1, HSV2, or HVP2. One clinical isolate of BV exhibited variation in a single
      restriction site, but its overall restriction pattern remained typical of BV.
      This method (PCR/RFLP) allowed the presence of herpesvirus DNA in clinical swabs
      from primates to be readily detected and the virus unambiguously identified.

PMID- 9249160
TI  - Polymerase chain reaction for detection of guinea pig adenovirus.
AB  - Lack of in vitro cultivation methods has inhibited the development of rapid,
      reliable diagnostic procedures for adenovirus-associated necrotizing
      bronchopneumonia in guinea pigs. Because polymerase chain reaction (PCR)
      techniques are well established for human adenoviruses, primers for the
      amplification of guinea pig adenovirus DNA were evaluated. The DNA for PCR was
      purified from the lung tissue of spontaneously infected and healthy guinea pigs.
      Adenovirus DNA could only be detected in the lungs of the infected animals.
      Subsequent sequence analysis of PCR products revealed that the guinea pig
      adenovirus is a distinct adenovirus.

PMID- 9249161
TI  - Immunohistochemical detection of Haemophilus parasuis serovar 5 in formalin
      fixed, paraffin-embedded tissues of experimentally infected swine.
AB  - An avidin-biotin complex immunohistochemistry technique was developed to detect
      Haemophilus parasuis serovar 5 in experimentally infected 18-21-day-old
      conventional pigs, using a rabbit polyclonal antiserum. Seven of 10
      intratracheally inoculated animals developed a low to medium degree of fibrinous
      polyserositis; meninges and pleura were the most severely affected areas.
      Haemophilus parasuis was recovered from 9 of 10 pigs; in 2 of them H. parasuis
      was isolated from tracheal swabs only. Positive immunohistochemistry results,
      mainly observed as free bacteria or bacteria within inflammatory cell cytoplasm
      in the fibrinopurulent exudate, were observed in 8 of 10 animals. Cross
      reactivity with Actinobacillus pleuropneumoniae was detected but not with other
      gram-positive and gram-negative bacteria tested. This immunohistochemistry
      technique seemed to be at least as sensitive as microbiologic cultures and could
      be useful in studies of pathogenesis and retrospective diagnosis. However, cross
      reactivity with A. pleuropneumoniae means that positive immunohistochemistry
      results in lung tissue from field cases would be dubious.

PMID- 9249162
TI  - Detection of Mycobacterium bovis in formalin-fixed, paraffin-embedded tissues of
      cattle and elk by PCR amplification of an IS6110 sequence specific for
      Mycobacterium tuberculosis complex organisms.
AB  - A presumptive diagnosis of tuberculosis can be made if a tissue has
      characteristic histopathologic changes and acid-fast organisms. However,
      definitive diagnosis requires culture and species identification of the causative
      mycobacterium, a process that takes several weeks to complete. The purpose of
      work reported here was to determine if formalin-fixed, paraffin-embedded tissues
      could be tested by polymerase chain reaction (PCR) to provide a more rapid
      diagnosis of tuberculosis. Nondecalcified tissues from cases of tuberculosis in
      cattle and elk (Cervus elaphus) were examined. The primers used for PCR amplified
      a 123-bp fragment of IS6110, an insertion sequence that is specific for organisms
      in the Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, M. microti,
      M. africanum). The PCR test detected this sequence in tissues from 92 of 99 (93%)
      tuberculosis cases, including 3 of 4 elk. In 80 tissues, the positive results
      were obtained using material prepared by immersion of paraffin sections in water
      containing a detergent, followed by alternating boil/freeze cycles. The remaining
      positive results were obtained with DNA isolated from the crude tissue extracts
      by proteinase K digestion and phenol/chloroform purification. Accuracy of the
      IS6110 PCR test was demonstrated by negative test results on 31 tissues that had
      either nonmycobacterial granulomas or granulomatous lesions caused by other
      mycobacteria (M. paratuberculosis or M. avium). The findings of this study show
      that a PCR test usually can provide a rapid diagnosis of tuberculosis when it is
      applied to paraffin sections that have characteristic lesions and acid-fast
      organisms.

PMID- 9249163
TI  - Otitis media in preweaned Holstein dairy calves in Michigan due to Mycoplasma
      bovis.
AB  - Mycoplasma bovis was isolated from the tympanic bullae of dairy calves with an
      exudative otitis media. The history, clinical signs, gross and histologic
      lesions, and bacteriologic findings are described for 5 preweaned Holstein calves
      with otitis media from a 600-cow dairy in Michigan. Clinical findings consisted
      of unilateral or bilateral ear droop, epiphora, head tilt, and recumbency in
      severely affected calves. Postmortem examination revealed unilateral or bilateral
      fibrinosuppurative to caseous exudate in the tympanic bullae. Histologically, a
      marked fibrinosuppurative to caseous exudate filled the tympanic air spaces. The
      partially ulcerated tympanic mucosa was markedly thickened with mononuclear cell
      infiltration and proliferation of fibrous connective tissue. Bone remodeling and
      periosteal hyperostosis were present in some osseous septa. Mycoplasma bovis was
      isolated from the tympanic bullae of all 5 calves and from the lungs of 2 calves
      and the frontal sinus of 1 calf. Mycoplasma bovis was isolated at > 100,000
      colony forming units/ml from the bulk milk tank of the farm of origin. The
      isolation of M. bovis from the bulk milk tank, indicating subclinical mycoplasmal
      mastitis coupled with the feeding of waste milk from mastitic cows to calves is
      suggestive of a possible source of the infection resulting in otitis media in
      preweaned dairy calves.

PMID- 9249165
TI  - Validation of nonradioactive chemiluminescent immunoassay methods for the
      analysis of thyroxine and cortisol in blood samples obtained from dogs, cats, and
      horses.
AB  - The performances of a radioimmunoassay method, a chemiluminescent immunoassay
      method, and a chemiluminescent-enzyme immunoassay method were evaluated for the
      analysis of cortisol and total thyroxine in blood samples obtained from dogs,
      cats, horses, and humans (reference samples). The analysis of cortisol in human
      and animal samples exhibited good precision, linearity, and recovery. The 3
      methods gave comparable values for the ACTH-induced increase and the
      dexamethasone-induced decrease in cortisol concentrations in animal samples. The
      recoveries of total thyroxine from human samples, analyzed by the 3 methods, were
      comparable. However, the basal total thyroxine concentrations determined by the
      chemiluminescent immunoassay method were 30-40% lower than those determined by
      the radioimmunoassay and the chemiluminescent-enzyme immunoassay methods in
      animal samples. In both human and animal samples, the plot of thyroxine values
      obtained by the radioimmunoassay method against those obtained by the
      chemiluminescent immunoassay method or the chemiluminescent-enzyme immunoassay
      method was linear. However, although the slope of the radioimmunoassay versus
      chemiluminescent-enzyme immunoassay curve was close to unity, the slope of the
      radioimmunoassay versus chemiluminescent immunoassay curve was 0.6. This result
      suggests that, compared with the radioimmunoassay method, the chemiluminescent
      immunoassay method underestimated thyroxine values in animal samples but not in
      human samples. Although all 3 methods yielded comparable changes in thyroxine
      concentrations in response to thyroid stimulating hormone, they did not yield
      comparable thyroxine concentrations in response to T3 suppression in dogs and
      cats.

PMID- 9249164
TI  - Detection of canine parvovirus in naturally infected dogs with enteritis and
      myocarditis by in situ hybridization.
AB  - An improved method for the diagnosis of canine parvovirus using in situ
      hybridization in standard formalin-fixed, paraffin-embedded tissue sections was
      developed. A digoxigenin-labeled probe complementary to DNA sequences that code
      for the entire sequence of the capsid protein VP-1 and the middle part of the
      sequence of the capsid protein VP-2 was designed. Specific histologic
      localization of canine parvovirus-infected cells was demonstrated in small
      intestine, tonsil, lymph node, thymus, spleen, heart, liver, and kidney from dogs
      diagnosed at necropsy with canine parvovirus infection. The in situ hybridization
      accurately pinpointed the specific sites of viral infection. The detection of
      canine parvovirus in liver, kidney, and heart tissues together in the same pups
      could represent an enhanced virulence of this strain of canine parvovirus and
      suggests a broadened tissue tropism not seen before in Korean strains of canine
      parvovirus.

PMID- 9249166
TI  - Sodium toxicity and pathology associated with exposure of waterfowl to
      hypersaline playa lakes of southeast New Mexico.
AB  - Cause of mortality was studied in waterfowl in hypersaline playa lakes of
      southeast New Mexico during spring and fall migration. Mortality was not common
      in wild ducks resting on the playas during good weather. However, when birds
      remained on the lakes for prolonged periods of time, such as during experimental
      trials and stormy weather, a heavy layer of salt precipitated on their feathers.
      Sodium toxicity was the cause of death for all experimental mallards housed on
      playa water and for 50% of the wild waterfowl found moribund or dead during the
      spring of 1995. Gross lesions included heavy salt precipitation on the feathers,
      ocular lens opacities, deeply congested brains, and dilated, thin-walled, fluid
      filled cloacae. Microscopic lesions in the more severely affected birds included
      liquefaction of ocular lens cortex with lens fiber swelling and multifocal to
      diffuse ulcerative conjunctivitis with severe granulocytic inflammation, edema,
      and granulocytic vasculitis resulting in thrombosis. Inflammation similar to that
      seen in the conjunctiva occasionally involved the mucosa of the mouth, pharynx,
      nasal turbinates, cloaca, and bursa. Transcorneal movement of water in response
      to the hypersaline conditions on the playa lakes or direct contact with salt
      crystals could induce anterior segment dehydration of the aqueous humor and
      increased osmotic pressure on the lens, leading to cataract formation.

PMID- 9249167
TI  - Multiplex polymerase chain reaction for simultaneous detection of Lawsonia
      intracellularis, Serpulina hyodysenteriae, and salmonellae in porcine intestinal
      specimens.
AB  - Proliferative enteritis, swine dysentery, and porcine salmonellosis are the most
      common enteric bacterial diseases affecting pigs in the growing and finishing
      stages of production. Currently, diagnoses of these diseases by standard cultural
      techniques of intestinal specimens can be laborious, time consuming, and
      expensive (swine dysentery, porcine salmonellosis) or impossible (proliferative
      enteritis). Amplification by polymerase chain reaction (PCR) of DNA sequences
      specific for each bacterial agent is a highly sensitive and specific method that
      overcomes the limitations associated with standard detection methods. A multiplex
      PCR (M-PCR) assay was developed for simultaneous detection and identification of
      the etiologic agents associated with proliferative enteritis, swine dysentery,
      and porcine salmonellosis in a single reaction using total DNA obtained directly
      from intestinal specimens. Purified DNA obtained from pure cultures of each
      bacterial agent alone or mixed in different combinations and concentrations and
      total DNA from intestinal specimens were amplified using the Lawsonia
      intracellularis-, Serpulina hyodysenteriae-, and salmonellae-specific M-PCR
      assay. Intestinal specimens consisted of feces and mucosal scrapings obtained
      from field cases of each disease alone or in combinations and feces obtained from
      pigs challenged with S. hyodysenteriae. The banding pattern of the amplified PCR
      products, after agarose gel electrophoresis and staining, indicated the presence
      of individual or combinations of etiologic agents in each specimen. Results from
      this study indicated that simultaneous amplification of L. intracellularis-, S.
      hyodysenteriae-, and salmonellae-specific DNA sequences by M-PCR can be used for
      specific detection and identification of three major enteric bacterial pathogens
      associated with proliferative enteritis, swine dysentery, and porcine
      salmonellosis occurring alone or in combinations. Also, the M-PCR assay can be
      done using DNA obtained directly from intestinal specimens submitted for
      diagnostic investigation.

PMID- 9249168
TI  - Distribution of cytopathic and noncytopathic bovine viral diarrhea virus antigens
      in tissues of calves following acute experimental infection.
AB  - The distribution of cytopathic and noncytopathic biotypes of bovine viral
      diarrhea virus (BVDV) in the tissues of colostrum-fed and colostrum-deprived
      calves was investigated. Colostrum-fed (group A) and colostrum-deprived (group B)
      calves were experimentally infected with the BVDV isolate 80/1, which contains
      both BVDV biotypes. Colostrum-deprived calves were also experimentally infected
      with a noncytopathic BVDV (group C) or with a cytopathic BVDV (group D) cloned
      from the 80/1 isolate. All calves were sequentially euthanized, and a wide range
      of tissue samples were processed for immunofluorescent and virus isolation
      studies. In group A, consistent immunofluorescent staining for BVDV was detected
      in vascular smooth muscle of numerous blood vessels in the tissues examined,
      mainly at 11 and 13 days postinoculation. A predominance of samples containing
      cytopathic BVDV was observed in the calves of this group, following virus
      isolation studies. Both cytopathic and noncytopathic BVDV were detected/recovered
      from a larger range of specimens in the calves in group B than from the calves in
      group A. In the calves in all the experimental groups, large amounts of BVDV
      antigen were detected mainly in tissue samples from the lymphoid and
      gastrointestinal systems, whereas only minimal amounts of BVDV were detected in
      the respiratory tract. Abundant noncytopathic BVDV antigen was also detected in
      pituitary gland and in Langerhans islets in pancreases of colostrum-deprived
      calves infected with the cloned noncytopathic BVDV. Noncytopathic BVDV was
      isolated from a wider range of tissues from calves in group C than in the
      colostrum-deprived calves infected with both BVDV biotypes. A cytopathic BVDV was
      isolated/detected in retropharyngeal, mesenteric, and abomasal lymph nodes and in
      thymus of 2 calves in group C. Cytopathic BVDV was detected/isolated mainly from
      mesenteric lymph nodes and Peyer's patches of the calves in group D.

PMID- 9249169
TI  - Evidence of Brucella infection in Parafilaroides lungworms in a Pacific harbor
      seal (Phoca vitulina richardsi).

PMID- 9249170
TI  - A 12-year retrospective study of equine abortion in Michigan.

PMID- 9249171
TI  - Internal hydrocephalus of channel catfish fry (Ictalurus punctatus).

PMID- 9249172
TI  - Evaluation of a competitive ELISA for detection of antibodies to epizootic
      hemorrhagic disease virus of deer.

PMID- 9249173
TI  - Equine gastric impaction, ulceration, and perforation due to persimmon (Diospyros
      virginiana) ingestion.

PMID- 9249174
TI  - Multimeric analysis of von Willebrand factor in animal plasmas using sodium
      dodecyl sulfate agarose gel electrophoresis, semidry electrotransfer, and
      immunoperoxidase detection.

PMID- 9249175
TI  - Acute granulocytic leukemia in a slaughter goat.

PMID- 9249176
TI  - An outbreak of listeriosis in a breeding colony of chinchillas.

PMID- 9249177
TI  - Apparent Clostridium haemolyticum/Clostridium novyi infection and exotoxemia in
      two horses.

PMID- 9249178
TI  - Immunohistologic diagnosis of pseudorabies (Aujeszky's disease) using monoclonal
      antibodies.

PMID- 9249179
TI  - Comparative performance of four serodiagnostic procedures for detecting bovine
      and equine vesicular stomatitis virus antibodies.

PMID- 9249180
TI  - Pyogranulomatous encephalitis associated with an unidentified Sarcocystis neurona
      like organism in a horse.

PMID- 9249181
TI  - Immunohistochemical detection of porcine reproductive and respiratory syndrome
      virus antigen in neurovascular lesions.

PMID- 9249182
TI  - Serotyping Actinobacillus pleuropneumoniae by the use of monoclonal antibodies.

PMID- 9249183
TI  - Spontaneous herpes simplex virus infection in common marmosets (Callithrix
      jacchus).

PMID- 9249184
TI  - Trends in dental health among Icelandic urban children.
AB  - Caries experience, oral hygiene and caries-related salivary parameters were
      recorded in a 20% representative sample of 12-year-old schoolchildren in
      Reykjavik, Iceland in 1991. The majority of the children was re-examined 3 years
      later in 1994. Trends in prevalence of caries and salivary bacteria were assessed
      by comparison with an analogous earlier longitudinal study (1984-87). Mean DFS
      values for 12-year-olds were 12.1 and 4.1, for 15-year-olds 23.3 and 11.3 in the
      earlier and later study, respectively. Reduction in DFS was 66% and 52% for the
      respective age groups. The decline was most pronounced in the group with low
      caries prevalence. Trends in caries experience were paralleled by salivary
      bacteria. The mean caries scores and frequency distributions of 15-year-olds in
      1994 closely resembled those of 12-year-olds a decade earlier, suggesting a delay
      rather than a true fall in caries prevalence.

PMID- 9249186
TI  - Representation of verbal pain descriptors on a visual analogue scale by dental
      patients and dental students.
AB  - Verbal rating scales (VRS), composed of ranked pain descriptors, are often
      employed in pain research. Factors that may influence the subjective pain
      intensity values, however, are not well established. In this study, 5 common pain
      descriptor adjectives were represented on a visual analogue scale (VAS) by a
      group of 80 dental students, by a group of 48 patients undergoing periodontal
      therapy, and by a group of 31 dental phobic patients. It was thought that each
      group of individuals on conducting the test represented a different degree of
      apprehension, ranging from a relaxed to a very tense status. There were
      differences in the interpretation of the pain descriptors between groups.
      Furthermore, age seemed to influence the interpretation of the pain descriptors.
      No correlation was found with gender. The descriptors did not divide the analogue
      scale into equal segments. 71% of all subjects gave the adjective "mild" a lower
      pain intensity representation than the adjective "weak", while the order was
      reversed among remaining subjects. Findings cast doubt on the reliability of VRS
      and the data handling methods commonly adopted in clinical pain research.

PMID- 9249185
TI  - Pulp calcifications in traumatized primary incisors. A morphological and
      inductive analysis study.
AB  - The purpose of this study was to investigate histopathological changes in primary
      teeth following trauma, and to look for possible correlations between the
      morphology of pulpal calcification and clinical findings. The material consisted
      of 123 primary teeth from 98 Danish children aged 9-108 months (mean age 33.5 +/-
      19.7 months) at the time of injury. The specimens were analyzed by means of light
      and scanning and transmission electron microscopy. Data from the clinical
      investigation and from predetermined ranked parameters from the histological
      analysis were processed in a computerized inductive analysis program. The
      results, describing patterns of co-variation, are presented as a decision tree.
      The most common diagnosis was intrusion luxation (54%). In 41% of all teeth, the
      degree of obliteration was less than 1/4 of the pulpal lumen. In most cases
      (79%), no denticles were visible. When present, 80% of the denticles had a bone
      like appearance. Tissues occluding the pulpal lumen were either dentin-like
      (49%), bone-like (19%), or fibrotic (9%). It could be concluded that these
      varying responses could not be correlated with explicit clinical diagnoses.
      However, in certain combinations, histological parameters could be correlated to
      clinical findings.

PMID- 9249187
TI  - Assessment of patients with direct conditioned and indirect cognitive reported
      origin of dental fear.
AB  - This study investigated the reported conditioned or cognitive origin of dental
      phobia in 100 adult patients at a specialized dental phobia clinic. It was shown
      that a majority of patients reported a conditioned background to their dental
      fear. Patients' avoidance time and level of dental anxiety corresponded to
      previously reported data for fearful groups. Individuals with an arousal
      conditioning etiology of dental fear reported significantly longer avoidance time
      as compared to individuals with a cognitively learned reaction. With the
      exception of an elevated level of general fears, most psychometrically assessed
      emotional reactions were well within normal ranges. However, patients with a non
      conditioned, cognitive etiology reported significantly higher levels of trait
      anxiety and fear of embarrassment. In addition, a separate analysis among women
      revealed a greater fear of physical injuries among patients with cognitive
      etiology.

PMID- 9249188
TI  - Comparison between cephalometric classification methods for sagittal jaw
      relationships.
AB  - The present study evaluated how 2 widely used cephalometric sagittal analyses,
      ANB angle and WITS appraisal, classify skeletal classes I, II, and III in a
      random selection of 497 Finnish boys aged 4-20 years. This distribution was also
      compared with the visual inspection of cephalometric structures judged by 2
      university instructors in orthodontics. The results showed remarkable differences
      and even sparked controversy concerning classification of the sagittal jaw
      relationships. The ANB angle and the WITS appraisal emphasized the role of class
      II based on a failure to distinguish the proportion of class I. The low-angle
      influence skewed the distribution of the ANB pattern in the class III direction,
      and the WITS pattern, conversely, towards class II. High- or low-angle influence
      had only minor effects on the visual inspection of cephalometric structures. This
      cross-sectional study showed an age-related decreasing mean value for the ANB
      angle and increasing mean value for the WITS appraisal, thus explaining the
      remarkable difference in the distribution of sagittal classes. However, the
      findings of age-related changes makes the use of the fixed norms questionable.
      For extreme or controversial cephalometric interpretations, visual inspection
      provides an essential aid in diagnosis and skeletal classification.

PMID- 9249189
TI  - Indicators of salivary gland inflammation in primary Sjogren's syndrome.
AB  - The aim of this study was to establish additional indicators in saliva and plasma
      which are associated with salivary gland inflammation in patients with primary
      Sjogren's syndrome (SS). ELISA assays were used to determine the concentrations
      of sICAM-1, sVCAM-1, sIL-2R alpha, IgA, IgG, calprotectin and albumin in parotid
      saliva, whole saliva and plasma samples. Soluble ICAM-1 was present in whole and
      parotid saliva samples from primary SS patients. Soluble VCAM-1 and sIL-2R alpha
      could not be detected in salivary samples from either primary SS or control
      subjects. IgA, IgG, calprotectin and albumin concentrations were higher in both
      whole and parotid saliva in the patient group compared with the control group.
      The results showed increased levels of calprotectin in all saliva samples
      compared to plasma, suggesting that calprotectin may be locally produced.
      Increased plasma values of sICAM-1, sVCAM-1, sIL-2R alpha, IgA, IgG and
      calprotectin were detected in primary SS patients when compared to controls. The
      output/min of IgA, IgG, calprotectin and albumin was decreased in SS patients.
      Plasma levels of various proteins could offer information concerning glandular
      and extraglandular inflammatory processes. However, salivary levels of these
      proteins (particularly sICAM-1) tend to reflect more the local inflammatory
      activity, providing a convenient and non-invasive tool for diagnosis.

PMID- 9249190
TI  - Potential side effects of dental amalgam restorations. (I). An oral and medical
      investigation.
AB  - The aim of this study was to explore a possible association between health status
      and self-reported adverse effects related to dental amalgam restorations. A group
      of 50 consecutive patients (index group), referred for complaints self-related to
      dental amalgam restorations, was compared with a control group of individuals
      matched by age, sex and postal zip code. The patients underwent an oral,
      stomatognathic, medical and clinical chemistry examination. Mercury levels were
      examined in blood, urine and hair. The results revealed that somatic diseases
      were more common in the index group (38% versus 6%). Symptoms related to cranio
      mandibular dysfunction were reported by 74% of the patients in the index group
      versus 24% in the control group, and were diagnosed in 62% and 36%, respectively.
      The oral health status and the number of amalgam surfaces were similar in the 2
      groups. No positive skin patch test to mercury was found in any of the groups.
      The estimated mercury intake from fish consumption, occupational exposure, and
      mercury levels in blood and urine were also similar and far below levels, where
      negative health effects would be expected. The correlation between the number of
      amalgam surfaces and mercury levels in plasma and urine (r=0.43) indicated a
      release of mercury from dental amalgam restorations in both groups. Since the
      mercury levels were similar among index patients and controls, mercury was not a
      likely cause of the impaired health reported by the patients.

PMID- 9249191
TI  - Potential side effects of dental amalgam restorations. (II). No relation between
      mercury levels in the body and mental disorders.
AB  - A group of 50 consecutive patients, referred for self-reported complaints which
      they related to dental amalgam restorations, was compared with control patients
      matched by age, sex and postal zip code. All patients were subjected to a
      psychiatric examination and a set of rating scales and questionnaires, and the
      symptoms were related to the mercury levels in blood, urine and hair. A
      psychiatric diagnosis was established in 70% of the patients in the index group
      versus 14% in the control group. The prevailing symptoms were anxiety, asthenia
      and depression. Mercury levels in blood, urine and hair were similar among index
      cases and controls, and were far below critical levels of mercury intoxication.
      There was no correlation between mercury levels and the severity of the reported
      symptoms. Therefore, mercury was not a likely cause of the complaints. Instead,
      the reported symptoms were part of a broad spectrum of mental disorders.

PMID- 9249192
TI  - Impact of nocturnal bruxism on mercury uptake from dental amalgams.
AB  - The mercury (Hg) release from dental amalgam fillings increases by mechanical
      stimulation. The aim of this study was to investigate the possible impact of
      nocturnal bruxism on Hg exposure from dental amalgams and to evaluate the effect
      of an occlusal appliance. 88 female patients from an orofacial pain clinic with a
      complete maxillary and mandibular dentition, a normal frontal vertical overbite
      with cuspid guidance, and at least 4 occlusal amalgam fillings in contact with
      antagonists in intercuspidal position, were examined with the Bruxcore bruxism
      monitoring device to measure the level of on-going nocturnal bruxism. Based on
      the degree of abrasion recorded, the subjects were divided into a group defined
      as bruxists, (n = 29), another group defined as non-bruxists, (n = 32), serving
      as controls, the intermediate group being discarded. The Hg exposure was assessed
      from the Hg concentration in plasma and urine, corrected for the creatinine
      content. In a regression model with bruxism as the only explanatory variable, no
      significant effect of bruxism was found, but when the number of amalgam fillings,
      chewing gum use, and other background variables were taken into account, there
      was a limited impact of bruxism on Hg in plasma. The nocturnal use of an occlusal
      appliance did not, however, significantly change the Hg levels. This study
      indicates that mechanical wear on amalgams from nocturnal bruxism may increase
      the Hg uptake, but the magnitude of this effect seems to be less than from the
      use of chewing gum.

PMID- 9249193
TI  - Caries and plaque inhibition in rats by five topically applied dentifrices.
AB  - The effectiveness of 5 different brands of dentifrices on caries and plaque were
      tested in rats in 2 experiments. 10 litters of rats each were infected with
      Streptococcus sobrinus OMZ-176 and Actinomyces viscosus Ny1. The rats were
      offered the diet 2000a containing either 40% of sucrose (study I) or 10% of
      sucrose (study II). The following products were tested topically: (1) H2O,
      (negative control); (2) chlorhexidine diacetate, (positive control); (3)
      Parodontax NF; (4) Meridol; (5) Colgate Total; (6) Mentadent C; (7) Dent Xpress.
      Comparisons with the water control in study I showed that plaque extent was
      decreased by chlorhexidine diacetate, Dent Xpress and by Mentadent C only. All
      fluoride-containing dentifrices tested reduced caries. In study II, comparisons
      with the water control showed that plaque extent was reduced by chlorhexidine
      diacetate, Parodontax, Meridol, Dent Xpress and by Mentadent C. All dentifrices
      reduced caries, however, the incidence was low. These 2 studies confirm that
      fluorides incorporated in dentifrices decrease dental caries in the rat.
      Differences in the effectiveness of caries inhibition between the 5 dentifrices
      could not be explained either by the form of fluoride utilized or by the
      antimicrobials added. Rather, the performance of a given dentifrice depended upon
      the concerted action of the particular ingredients. It appears that the effect of
      antiplaque agents should be evaluated in the rat model using a diet containing
      sucrose at a low level.

PMID- 9249194
TI  - Expression and splicing of the fibronectin gene in healthy and diseased
      periodontal tissue.
AB  - Fibronectin is a major component of the extracellular matrix and is considered to
      have an important role in chronic inflammatory periodontal disease. The
      fibronectin gene product has been shown to be subject to alternative splicing in
      3 regions, each generating different mRNA transcripts associated specifically
      with normal adult tissue, embryogenesis, tissue regeneration, and wound healing.
      In the present study, using the reverse-transcribed polymerase chain reaction to
      examine splicing profiles of the primary transcript, we found that healthy
      periodontal tissue expressed all alternatively spliced embryonic isoforms,
      indicative of the extensive and ongoing rebuilding processes which occur in these
      tissues. In marked contrast, only the exon-skipped transcripts were generated in
      tissue from chronic inflammatory periodontal disease patients. The loss of the
      high molecular weight isoforms in lesional tissues may be due to the excess
      production of inflammatory mediators in this disease, since we observed that high
      concentrations of the cytokine IL-1beta caused down-regulation of these
      transcripts in normal periodontal cells in tissue culture. Moreover, we also
      demonstrated that growth factors likely to be involved in periodontal
      regeneration and repair, such as PDGF, IGF-1 and TGF-beta, elicited pronounced
      upregulation of the embryonic isoforms of fibronectin in these cells. Although
      the functional activities of the antigens corresponding to the alternatively
      spliced variants of fibronectin are not yet known, our finding that they are
      selectively expressed suggests that they have highly specific roles in both
      periodontal breakdown and repair.

PMID- 9249195
TI  - Expression of hsc 70, but not hsp 70, in human third molar dental pulp.
AB  - The constitutive (hsc 70) and inducible (hsp 70) isoforms of heat shock protein
      70 are important members of the superfamily of stress related proteins that
      protect and promote the recovery of cells from physiological and pathologic
      stress. The goal of this study was to define the baseline expression of hsc 70
      and hsp 70 in disease-free, minimally stressed human dental pulp of the adult 3rd
      molar. Immunolocalization demonstrated moderate to heavy staining intensity for
      hsc 70 in both the cytoplasm and nucleus of odontoblasts and fibroblasts
      comprising the human pulp. Endothelial and smooth muscle cells displayed weak to
      moderate immunoreactivity for hsc 70 in both the cytoplasm and nucleus. Schwann
      cells demonstrated only weak nuclear staining for hsc 70. No immunoreactivity for
      hsp 70 was observed in any cell type in human pulp. Western, northern, and RT-PCR
      analysis of pulp preparations confirmed the expression of hsc 70 mRNA and protein
      within components of the pulp. These results demonstrate that cells of the human
      pulp express, under conditions of minimal stimulation, a key component of the
      stress response protein superfamily. The expression of hsc 70 under conditions of
      minimal stress may provide pulp components an advantage in resisting cell injury
      when stress occurs.

PMID- 9249196
TI  - The Maillard reaction in demineralized dentin in vitro.
AB  - The Maillard reaction between carbohydrate and protein has been proposed as a
      cause of the browning of carious lesions. The aim of the present investigation
      was to determine the occurrence of this reaction in bovine dentin collagen in
      vitro and to establish the effect of the reaction on the proteolytic degradation
      of bovine dentin collagen in vitro. Slices of demineralized bovine dentin were
      incubated with 0.2 M glucose or buffer for 10 weeks at 37 degrees C. The
      formation of initial (furosine) and advanced (pentosidine) products of the
      Maillard reaction in dentin exposed to glucose was confirmed by HPLC. After
      reduction with NaBH4 to prevent intermediate Maillard products from further
      reaction, slices were either degraded with collagenase for fluorescence
      measurement or incubated with trypsin or pepsin to assess enzymatic degradation.
      Fluorescence characteristic for the Maillard reaction increased in glucose
      exposed slices. Degradation of collagen by pepsin, but not by trypsin, was
      greatly depressed following glucose pretreatment. This may indicate an altered
      sensitivity to proteolytic degradation; the Maillard reaction thus has a
      potential role in caries arrestment.

PMID- 9249197
TI  - Inhibitor-resistant beta-lactamases.

PMID- 9249198
TI  - Non-inducible, mainly cell-associated beta-lactamase from Nocardia asteroides
      strain 108.
AB  - The beta-lactamase of the soil-borne strain 108 (parental strain) of Nocardia
      asteroides is a non-inducible enzyme mainly associated with the cells; it can be
      efficiently extracted by ultrasonication and SDS treatment. Crude enzyme
      preparations showed penicillinase and cephalosporinase activity. The kinetics of
      beta-lactamase production and in-vitro susceptibility to combinations of beta
      lactam antibiotics plus beta-lactamase inhibitors have been studied in two stable
      overproducer mutants (A14 and B1) obtained by mutagenization of the parental
      strain with nitrosoguanidine. The cell-associated enzyme increased with bacterial
      growth in parental and mutant strains and was particularly abundant in stationary
      phase cells. The beta-lactamase inhibitors sulbactam and clavulanic acid
      decreased MIC values of penicillins more efficiently in the parental strain than
      in mutants, thus indicating some involvement of the enzyme in the resistance of
      N. asteroides strain 108 to beta-lactam antibiotics.

PMID- 9249199
TI  - Susceptibility testing of Stenotrophomonas maltophilia to carbapenems.
AB  - The susceptibility of 20 clinical isolates of Stenotrophomonas maltophilia to the
      carbapenems imipenem and meropenem was investigated by various methods. S.
      maltophilia appeared sensitive to meropenem but resistant to imipenem by disc
      testing in Iso-sensitest agar. Agar dilution MICs were performed using Iso
      sensitest agar and with incubation under three sets of atmospheric conditions.
      MICs of meropenem were considerably lower than those of imipenem; this effect was
      maximal after incubation in 5% CO2 when the MIC of meropenem was approximately 64
      times less than that of imipenem. Induction experiments showed that both
      carbapenems could induce production of the L1 carbapenemase. However, disc
      approximation tests showed that imipenem could induced resistance to meropenem.
      Partially stably derepressed mutants were readily selected in vitro. We conclude
      that, although S. maltophilia may give large zones of inhibition to meropenem on
      disc testing, resistant mutants are readily selected and therefore standard
      sensitivity tests may be poorly predictive of clinical outcome of treatment of S.
      maltophilia infections with meropenem.

PMID- 9249201
TI  - In-vitro activities of aminoglycoside-aminocyclitols against mycobacteria.
AB  - Aminoglycoside-aminocyclitols including streptomycin, kanamycin, capreomycin and
      amikacin showed considerable activity against Mycobacterium tuberculosis, with
      MICs well below their Cmax and relatively low MBC/MIC ratios. Kanamycin,
      capreomycin and amikacin remained highly active against 'resistant' and
      'multidrug-resistant' M. tuberculosis isolates except for some 'multidrug
      resistant' isolates which showed complete cross-resistance between streptomycin
      and the selected 2-deoxystreptamines. Gentamicin displayed anti-tuberculous
      activity but was bacteriostatic only. Non-tuberculosis mycobacteria, in
      particular Mycobacterium chelonae and Mycobacterium avium-intracellulare, were
      more resistant than M. tuberculosis. Amikacin was inhibitory against
      Mycobacterium kanasii, Mycobacterium scrofulaceum and Mycobacterium fortuitum,
      but was bactericidal against M. scrofulaceum only. Kanamycin was also
      bactericidal against M. scrofulaceum. Growth of M. fortuitum was inhibited by
      amikacin and neomycin which was also inhibitory against M. tuberculosis and M.
      scrofulaceum. Although the application of neomycin has been limited by its high
      toxicity, this study suggested that this drug might be useful as a topical agent
      for cutaneous infections by M. fortuitum.

PMID- 9249200
TI  - In-vitro studies of two 5-nitroimidazole derivatives.
AB  - This paper reports the findings obtained using two new compounds belonging to the
      5-nitroimidazole family: sulphuridazole (V1) and sulphonidazole (V2). We first
      assessed their antimicrobial activity on Clostridia spp. and then extended the
      study to Gram-positive and Gram-negative aerobic microorganisms and to Candida
      albicans. Their MICs were compared with those of metronidazole. The findings show
      that the antibacterial and antimycotic activity of sulphonidazole is greater than
      that of sulphuridazole, while metronidazole is not active against any aerobic
      organism. It also emerges that the NO2 group is indispensable for all the
      microorganisms assayed and that sulphuridazole and sulphonidazole are the first
      two 5-nitroimidazoles active against C. albicans. The redox potentials of the 5
      nitroimidozoles studied suggest that their action mechanism is mainly based on
      redox processes.

PMID- 9249202
TI  - Evaluation of the post-antibiotic effect of six anti-mycobacterial agents against
      Mycobacterium avium by the Bactec radiometric method.
AB  - We compared and evaluated the duration of the post-antibiotic effect (PAE) of six
      anti-mycobacterial agents (ethambutol, isoniazid, rifampicin, amikacin,
      ciprofloxacin and clarithromycin), alone and in combination, against ten strains
      of Mycobacterium avium. PAE was determined by conventional viable counting and
      the Bactec growth system, analysed by the T100 value (the time to produce a
      cumulative growth index of 100). A 2 h exposure to the drug did not induce
      significant killing. Thus, comparison of regrowth could be evaluated without the
      potential need to adjust viable counts. The correlation of duration of PAE
      between the viable count method and the T100 Bactec method was excellent (r =
      0.94). No significant PAE (< 8 h) was induced using sub-inhibitory drug
      concentrations or with ethambutol or isoniazid alone. Rifampicin (20-41 h) and
      amikacin (8-36 h) demonstrated consistent and extended PAEs, while ciprofloxacin
      (1-15 h) and clarithromycin (2-10 h) displayed variable PAE activities. Different
      three-drug combinations (all including ethambutol) displayed variable results
      with a combination of ethambutol, isoniazid and rifampicin being the most
      effective combination for extending the PAE (> or = 8 h) which was observed in
      half the strains tested. It was concluded that the T100 Bactec method is highly
      suitable for evaluating PAE against M. avium, producing a definitive result in 5
      days.

PMID- 9249203
TI  - Correlation between bactericidal activity and postantibiotic effect for five
      antibiotics with different mechanisms of action.
AB  - Theoretically, if the postantibiotic effect (PAE) reflects the duration of
      cellular recovery, then the extent of cellular damage inflicted on bacteria by an
      antibiotic, as suggested by the degree of bactericidal activity, should reflect
      the length of PAE; this is especially true if binding of the antibiotic to
      bacterial receptors is irreversible. To test this hypothesis, correlation between
      PAEs and bactericidal rate constants measured simultaneously at various
      antibiotic concentrations was examined for five antibiotic-bacterium
      combinations. Each of the five antibiotics used, i.e. tobramycin, ciprofloxacin,
      dicloxacillin, trimethoprim and tetracycline, has a different mechanism of
      action: the first three bind irreversibly to bacterial receptors, while
      trimethoprim and tetracycline bind reversibly. Both PAE and bactericidal activity
      increased nonlinearly with concentrations in a saturable manner for all the
      combinations studied. Linear least-square regression analyses showed strong
      correlations (P < 0.01) between the two responses for individual combinations.
      Such a linear relationship also extended, with good correlation (P < 0.05),
      across the five combinations when individual maximal bactericidal rate constants
      and PAEs were considered separately. These observations suggest that cellular
      recovery from nonlethal damage following antibiotic exposure may be a major
      determinant of PAE.

PMID- 9249204
TI  - Action of new organometallic complexes against Leishmania donovani.
AB  - The action of 16 newly synthesized metal complexes having the general structure
      cis-Pt-(II)-Xn-Ln have been tested in vitro against the promastigote forms of
      Leishmania donovani. The metal complexes at 24 h and maximum dosages inhibited
      growth from 0%, e.g. in cis-Pt-nifurtimox, to 100%, e.g. in cis-Pt-(2,3,4,5,6
      pentafluoroaniline)2Br2 or cis-Pt-pentamidine-I2. A study of the cytotoxicty of
      these latter complexes on the phagocytic cell line J-774 showed neither high
      cytotoxicity nor cytolysis. At the maximum dosage after 24 h of permanent contact
      with the cells (extreme, non-physiological conditions), cytolysis did not exceed
      30%. For most of the compounds, cytolysis ranged from 0%, for cis-Pt-oxamniquine
      Cl2 to 27.7%, for cis-Pt-pentamidine-I2. The compound cis-Pt-(2,3,4,5,6
      pentafluoroaniline)2-Br2 caused up to 1.4% cytolysis under the above conditions.
      Parasites exposed to cis-Pt-pentamidine-I2 showed notably reduced DNA, RNA and
      protein synthesis, unlike those exposed to other compounds. Parasites examined by
      electron microscopy showed effects mainly on the nucleus, though in some cases
      the mitochondria were affected, altering the internal membranes of the
      cytoplasmic organelles. The in-vivo activity of the complex cis-Pt-guanethidine
      Cl2 was evaluated in parasitized Wistar rats, in which the number of amastigotes
      per gram of spleen was reduced by 75% compared with controls.

PMID- 9249205
TI  - Comparison of the in-vitro and in-vivo efficacy of FK037, vancomycin, imipenem
      and nafcillin against staphylococcal species.
AB  - The activity of methicillin, oxacillin, vancomycin, imipenem and FK037 against
      106 isolates of staphylococci was assessed using a microbroth dilution method
      with low (10(5) cfu/mL) and high (10(7) cfu/mL) inoculum sizes. Overall, FK037,
      an oxime-type cephem antibiotic, was as active as imipenem, but less active than
      vancomycin (MIC90s 25, 25 and 6.25 mg/L, respectively) at the lower inoculum.
      Efficiency of plating experiments were also performed to characterize phenotypic
      expression of resistance to FK037, imipenem and methicillin. Five of 24 isolates
      and 18 of 24 isolates contained subpopulations resistant to FK037 and imipenem,
      respectively. In a rabbit model of endocarditis, FK037 was equally effective as
      other antibiotics tested in the treatment of methicillin-sensitive Staphylococcus
      aureus infection. In the treatment of endocarditis due to a homotypic methicillin
      resistant S. aureus, FK037 and vancomycin were the most active antibiotics. The
      presence of subpopulations resistant to imipenem and FK037, as demonstrated by
      efficiency of plating and high inoculum MIC testing, did not correlate with
      antibiotic effectiveness in the rabbit model of endocarditis. Cultures of
      vegetation material following treatment with imipenem and FK037 demonstrated a
      lower frequency of organisms resistant to FK037 when compared with imipenem. Thus
      FK037 shows in-vitro and in-vivo activity against some methicillin-resistant
      staphylococcal species.

PMID- 9249206
TI  - Antimicrobial resistance in Salmonella enterica subsp. enterica serovar
      typhimurium from humans and production animals.
AB  - We have studied the frequency of antimicrobial resistance and epidemiological
      relatedness among 473 isolates of Salmonella enterica subsp. enterica serovar
      typhimurium (S. typhimurium) from human and veterinary sources. The human strains
      were clinical isolates from patients with diarrhoea sent to the State Serum
      Institute during August 1993 (228 isolates). The animal strains were isolated
      from clinical or subclinical infections in cattle (48 isolates), pigs (99
      isolates) or poultry (98 isolates), all from 1993. All strains were tested
      against 22 different antimicrobial agents used in both human and veterinary
      medicine with the tablet diffusion method. Strains were also phage-typed and the
      plasmid content determined in all resistant strains. Ribotyping was performed on
      selected strains. Of 228 human isolates tested, 19.3% of the strains were
      resistant to one or more antimicrobial agent compared with 10.4% of strains from
      cattle, 11.1% of strains from pigs and 9.2% of strains from poultry. Multiple
      resistance, i.e. resistance against at least four antimicrobial agents, was found
      in 9.2% of the human strains, but in only two of the cattle isolates. The
      majority of the multi-resistant strains in humans were from infections contracted
      outside Denmark, most often in southern Europe or south-east Asia. Resistance in
      human strains was most common against tetracycline (13%), ampicillin (12%),
      sulphonamide (12%), streptomycin (10%) and chloramphenicol (8%). The resistance
      pattern differed somewhat in animal isolates: Poultry strains were usually
      resistant only to ampicillin, while pig and cattle isolates were most often
      resistant to sulphonamide, tetracycline and streptomycin. Typing of the strains
      showed that some animal strains and human strains were indistinguishable. In
      conclusion, while antimicrobial resistance was present in S. typhimurium isolated
      from humans and animals in Denmark, multiple resistance was most often acquired
      outside Denmark.

PMID- 9249207
TI  - A flow cytometric study of antibiotic-induced damage and evaluation as a rapid
      antibiotic susceptibility test for methicillin-resistant Staphylococcus aureus.
AB  - Flow cytometry using the anionic membrane potential-sensitive fluorescent probe,
      bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4(3)), enabled
      assessment of antibiotic-induced membrane perturbation in five clinical isolates
      of methicillin-resistant Staphylococcus aureus (MRSA) and two antibiotic
      sensitive reference strains, NCTC 6571 and 8325-4, after establishment of steady
      state growth in liquid cultures inoculated from single colonies. Flow cytometric
      indications of the enhanced DiBAC4(3) uptake after treatment with vancomycin at
      0.1, 1, 4 and 10 x MIC showed excellent comparison with viability losses
      quantified as cfu on solid agar in MRSA isolate QC. The antibiotic susceptibility
      patterns to benzylpenicillin, methicillin and vancomycin for all isolates used in
      this study could be determined in 2-4 h from an overnight plate culture. This
      technique thus provides a rapid and reproducible antibiotic sensitivity test
      which may be applicable in routine clinical practice.

PMID- 9249208
TI  - Ketolides lack inducibility properties of MLS(B) resistance phenotype.
AB  - Ketolides belong to a new class of semi-synthetic 14-membered-ring macrolides,
      which differ from erythromycin A by having a 3-keto group instead of the neutral
      sugar L-cladinose. The ability of these molecules and their L-cladinose
      counterparts to induce MLS(B) resistance in staphylococci (one strain) and
      streptococci (two strains) was investigated using a disc agar susceptibility
      method as well as measuring induction kinetics. All 14- and 15-membered ring
      macrolides tested showed inducing activity. In contrast, ketolides were clearly
      unable to induce MLS(B) resistance, a result consistent with the high in-vitro
      activity of this new class of antibiotics against erythromycin A-inducible
      resistant bacteria.

PMID- 9249209
TI  - Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric
      fever.
AB  - Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults diagnosed
      with uncomplicated enteric fever and randomized to receive succinate ester 30
      mg/kg i.v. or i.m. Serial plasma concentrations of chloramphenicol, and
      iothalamate (to estimate glomerular filtration rate), antipyrine (hepatocellular
      function) and Indocyanine Green (liver blood flow) were measured by HPLC and
      kinetic parameters estimated by non-compartmental analysis. In culture-positive
      patients (n = 16), mean residence times (MRTs) and steady-state volumes of
      distribution (V(d)ss) for i.v. chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and
      1.9 +/- 0.8 L/kg; n = 7) were less than after i.m. chloramphenicol (12.3 +/- 7.3
      h and 3.7 +/- 2.5 L/kg; n = 9; P < 0.05), with a higher peak plasma concentration
      after i.v. (16.2 +/- 9.1 versus 7.8 +/- 3.6 mg/L; P < 0.05); plasma clearance
      (Cl(p)) was similar in the two groups (368 +/- 172 and 310 +/- 224 mL/kg/min
      after i.v. and i.m. respectively). In 17 patients examined during convalescence,
      MRT and Vdss were less than in acute illness regardless of route chloramphenicol
      administration. There were similar changes in chloramphenicol kinetic parameters
      in culture-negative patients. Antipyrine Cl(p) and liver blood flow correlated
      weakly with chloramphenicol Cl(p) in culture-positive patients (P < 0.1) and were
      higher in convalescence; no such associations were seen for iothalamate Cl(p).
      These data indicate that i.v. chloramphenicol produces peak plasma concentrations
      which are on average twice those after i.m. injection of the same dose, due
      principally to a smaller V(d)ss. Cl(p) is uninfluenced by route of administration
      and is determined more by hepatic metabolism than renal excretion. Intramuscular
      treatment may result in sub-therapeutic chloramphenicol concentrations initially,
      but continued regular i.v. dosing is more likely to produce levels at which bone
      marrow toxicity occurs.

PMID- 9249210
TI  - A comparison of the penetration of cefuroxime and cephamandole into bone, fat and
      haematoma fluid in patients undergoing total hip replacement.
AB  - Twelve patients undergoing total hip anthroplasty received, at the induction of
      anaesthesia, cephamandole (1 g) and cefuroxime (1.5 g); further doses of
      cephamandole (1 g) and cefuroxime (750 mg) were given at 8 and 16 h after the
      operation. Routine total hip arthroplasty was performed and at timed intervals
      during operation samples of bone, fat and blood were collected for assay for HPLC
      analysis. Samples of the haematoma fluid that formed around the operation site
      and further blood samples were also collected at 7 and 15 h after the operation.
      Although considerable variation was observed in the bone and fat concentrations
      of both agents, the cefuroxime levels were substantially higher than those of
      cephamandole, with mean values for bone of cefuroxime 36.0 mg/L (95% CI 29.0-43.0
      mg/L) and cephamandole 18.3 mg/L (95% CI 14.2-22.4 mg/L) and for fat of
      cefuroxime 15.0 mg/L (95% CI 11.1-18.9 mg/L) and cephamandole 11.2 mg/L (95% CI
      7.2-15.2 mg/L). When corrected for blood concentrations the penetration of both
      agents was similar (bone, 43.6% cefuroxime and 37.8% cephamandole; fat, 16.0%
      cefuroxime and 19.2% cephamandole). Cefuroxime concentrations in haematoma drain
      fluid were higher than those of cephamandole 6-8 h after the operation (17.8
      versus 8.3 mg/L) but lower at 14-16 h (7.7 versus 9.6 mg/L). We conclude that
      there are no significant differences between the bone, fat or haematoma
      penetration of cefuroxime and cephamandole and that any differences in the
      absolute levels of the two agents are due to differences in the total drug
      administered rather than their ability to penetrate into these sites. Time-kill
      curves for cefuroxime and cephamandole against five clinical isolates of
      Staphylococcus aureus failed to identify any significant differences between the
      rates of kill for the two agents at the concentrations seen in bone, fat or
      haematoma fluid. For both prophylaxis regimens antibiotic concentrations exceeded
      the MICs for potential pathogens for the duration of the operation and also in
      the haematoma which surrounds the operation site for up to 24 h after the
      operation.

PMID- 9249211
TI  - Decreased susceptibility to imipenem among penicillin-resistant Streptococcus
      pneumoniae.
AB  - We assessed the antimicrobial susceptibilities of 59 penicillin-intermediate or
      penicillin-resistant pneumococci. All strains were susceptible to vancomycin and
      rifampicin. The frequency of strains with decreased susceptibility to cefotaxime,
      chloramphenicol, imipenem and meropenem was 15, 31, 47 and 49% respectively. The
      high percentage of penicillin-intermediate or penicillin-resistant Streptococcus
      pneumoniae with decreased susceptibility to third-generation cephalosporins,
      chloramphenicol and carbapenems limits the therapeutic options for the treatment
      of invasive pneumococcal infections and particularly of meningitis.

PMID- 9249212
TI  - Amphotericin B resistance testing of Candida spp.: a comparison of methods.
AB  - Several methods of susceptibility testing were compared for their ability to
      detect amphotericin B resistance among yeast isolates, including isolates known
      to be amphotericin-B-resistant in an animal model. A microtitre MIC method using
      antibiotic medium no. 3 and Etest strips were able to discriminate susceptible
      and resistant isolates. A disc susceptibility test was also able to identify
      resistant isolates and this method may be suitable for routine use as a screening
      test. A survey of resistance in 644 clinical isolates showed that the incidence
      of elevated MICs (> or = 0.25 mg/L) was only 1.2%.

PMID- 9249213
TI  - Penetration of dapsone into cerebrospinal fluid of patients with AIDS.
AB  - It has been proposed that dapsone in combination with pyrimethamine could be used
      for prophylaxis of both Pneumocystis carinii pneumonia and encephalitis due to
      Toxoplasma gondii. Ten patients with AIDS undergoing lumbar puncture for
      diagnostic purposes were studied in order to assess the penetration of dapsone
      into CSF. Blood and CSF samples were obtained between 3 and 72 h following
      administration. Six patients had received oral dapsone for at least 1 month at
      the dosage regimen of 100 mg twice of three times weekly and four patients had
      received a single oral 100 mg dose. Dapsone concentration in CSF ranged from
      0.013 to 0.296 mg/L while concentrations in plasma ranged from 0.018 to 1.231
      mg/L. The CSF:plasma concentration ratio ranged from 0.21 to 2.01. The MIC of
      dapsone in combination with pyrimethamine against T. gondii is unknown, and
      further data are required to confirm whether the CSF concentrations of dapsone
      found in our study are sufficient to inhibit T. gondii growth in patients
      infected with human immunodeficiency virus (HIV). The high interpatient
      variability of dapsone CSF concentrations warrants further studies in selected
      categories of patients with HIV infection.

PMID- 9249214
TI  - Clinical response to ketoconazole of HIV-related oral candidosis is predicted by
      Odds' relative growth method of susceptibility testing.
AB  - In-vitro ketoconazole susceptibility was assessed by measuring an isolate's
      relative growth in medium containing a fixed concentration of ketoconazole as a
      percentage of growth in drug-free medium. One hundred specimens from HIV-positive
      patients with candidosis were tested. Each patient's response was assessed
      following one week's treatment with ketoconazole 400 mg/day. A relative growth in
      ketoconazole of >75% predicted clinical failure of ketoconazole with a
      specificity of 97% and sensitivity of 79%.

PMID- 9249215
TI  - The pharmacokinetics of intravenous ciprofloxacin 400 mg 12 hourly in patients
      with severe sepsis: the effect of renal function and intra-abdominal disease.
AB  - Serum concentrations of ciprofloxacin were reviewed in 22 patients given
      ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage
      modifications were made in patients with renal impairment. Patients who had
      either bowel or liver pathology in addition to renal failure had significantly
      higher serum concentrations than all other patients. Dosage reduction of
      ciprofloxacin in patients with severe sepsis and impaired renal function is not
      required unless they have co-existent intra-abdominal disease.

PMID- 9249216
TI  - Continuous infusion of ceftazidime in cystic fibrosis patients during home
      treatment: clinical outcome, microbiology and pharmacokinetics.
AB  - Acute exacerbations of Pseudomonas aeruginosa lung infections were treated with
      ceftazidime by continuous infusion in 17 adult patients with cystic fibrosis at
      home. Ceftazidime was delivered via an infusion pump and the effects of this 3
      week home intravenous antibiotic treatment (HIVAT) were prospectively studied
      over a 2 year period. Patients with cystic fibrosis (eight male and nine female
      patients; mean age 26.9 +/- 7.6 years, range 15-52 years), received a total of 33
      courses of continuous ceftazidime (100 mg/kg/24 h). Clinical data were collected
      at the start, the end and 4-6 weeks after the end of treatment in 12 patients.
      Ceftazidime pharmacokinetic data during continuous infusion were obtained from
      ten patients. The treatment was supervised by the clinician without home visits.
      All 25 clinically evaluable courses in 12 patients proved efficacious. The mean
      duration of the courses was 21 days. The entire antibiotic course was
      administered at home in 88% of the courses. The other 12% was started for 2-3
      days as an inpatient. Objective clinical parameters significantly improved.
      Clinical improvement was noted in 91% of the patients, and lasted at least until
      4-6 weeks after the end of the treatment in 70%. The number of cultures positive
      for P. aeruginosa decreased significantly during antibiotic treatment. Bacterial
      count returned to pretreatment values 4-6 weeks after treatment. Multiple courses
      of ceftazidime monotherapy did not result in a lasting increase of ceftazidime
      resistant pseudomonas strains. Total body clearance was 9.1 +/- 1.3 L/h. The
      steady-state ceftazidime serum concentration during continuous infusion was 28.4
      +/- 5.0 mg/L. Sputum concentrations were in the range of 0.5-13 mg/L (3.9 +/- 4.0
      mg/L). In conclusion, HIVAT with ceftazidime administered by continuous infusion
      proved clinically effective and did not result in an increase in lasting
      resistance.

PMID- 9249218
TI  - Lysogenic conversion as a factor influencing the vancomycin tolerance phenomenon
      in Staphylococcus aureus.

PMID- 9249217
TI  - Methicillin-resistant Staphylococcus aureus clinical strain with reduced
      vancomycin susceptibility.

PMID- 9249219
TI  - Safety and efficacy of Intralipid emulsions of amphotericin B.

PMID- 9249220
TI  - Macrolide resistance among Streptococcus pneumoniae and Streptococcus pyogenes
      isolates from out-patients in the USA.

PMID- 9249221
TI  - In-vitro susceptibilities of multiresistant strains of Acinetobacter baumannii to
      eight quinolones.

PMID- 9249222
TI  - Intracellular and extracellular killing of a penicillin-resistant, serotype-9
      strain of Streptococcus pneumoniae by polymorphonuclear leucocytes in the
      presence of sub-inhibitory concentrations of clavulanic acid.

PMID- 9249223
TI  - Successful use of tetracycline as therapy of an immunocompromised patient with
      septicaemia caused by a vancomycin-resistant enterococcus.

PMID- 9249224
TI  - Prophylaxis of mycobacterial infection and acquired drug resistance.

PMID- 9249225
TI  - Angiotensin II receptor antagonists, elite drugs (or not) for patients with heart
      failure or hypertension?

PMID- 9249226
TI  - Effects of calcium antagonists on the risks of coronary heart disease, cancer and
      bleeding. Ad Hoc Subcommittee of the Liaison Committee of the World Health
      Organisation and the International Society of Hypertension.

PMID- 9249227
TI  - Vitamin C and blood pressure--an overview.
AB  - BACKGROUND: Laboratory and some epidemiological studies suggest that
      antioxidants, such as vitamin C, are protective for cardiovascular disease. This
      protective effect may be mediated through blood pressure (BP). This is the first
      systematic review of epidemiological studies of vitamin C and BP. METHOD:
      Published cross-sectional studies, prospective studies and trials in humans were
      identified that examined the association between vitamin C intake or plasma
      vitamin C levels and BP. Relevant references were located by MEDLINE search 1966
      1996, EMBASE search 1980-1996, by searching personal bibliographies, books and
      reviews and from citations in located articles. RESULTS: Cross-sectional data
      were available from 18 populations. Ten of 14 reported an inverse association
      between plasma vitamin C and BP and three of four reported an inverse association
      with vitamin C intake. The two non-randomised and four randomised controlled
      trials were all small. Of the randomised trials one reported a significant
      decrease in BP, one a non-significant decrease and two were uninterpretable.
      CONCLUSIONS: We found a consistent cross-sectional association between higher
      vitamin C intake or status and lower BP, though no study controlled adequately
      for confounding by other dietary factors. Further cross-sectional studies are
      required to establish whether an independent association exists. If this is shown
      to be the case larger and longer term trials will be needed to confirm the
      association is causal. Potentially the impact on cardiovascular disease of a
      modest change in mean population vitamin C intake is large.

PMID- 9249228
TI  - Criteria of normal blood pressure and hypertension in Japanese preschool
      children.
AB  - The blood pressure (BP) of 5332 Japanese preschool children from 2 to 6 years of
      age was measured using an automated BP recorder (Dinamap Model 8104). The third
      reading of the consecutive measurement of BP was used for analysis. This study
      adopted a definition of hypertension developed by The Task Force conducted in the
      United States in 1987, which showed the 95th percentiles of systolic and
      diastolic BP for age and sex. Stepwise regression analysis revealed that body
      height, weight and heart rate had significant effects on both systolic and
      diastolic BP, whereas age had an effect on diastolic BP only, while sex and area
      where the subjects lived did not affect either BP. The 95th percentiles of
      systolic/diastolic BP at 2, 3, 4, 5, and 6 years of age were 115/69, 113/68,
      114/65, 118/67 and 116/69 mm Hg in boys, and 121/70, 114/69, 115/67, 118/68 and
      120/69 mm Hg in girls, respectively. The BP of Japanese preschool children can be
      evaluated using the data shown in this study.

PMID- 9249229
TI  - Blood pressure, insulin, and haematocrit values in Japanese subjects over 60
      years of age.
AB  - Many studies have suggested an association between blood pressure (BP) and both
      insulinaemia and haematocrit values in Western populations. However, relatively
      few data regarding such associations for the Japanese population are available.
      We investigated the relationship between BP and various parameters, including
      insulin and haematocrit, in 269 healthy Japanese individuals (113 men and 156
      women) over 60 years of age. The data were analysed by stepwise multiple
      regression analysis. In men, the most important determinant of systolic BP (SBP)
      and diastolic BP (DBP) was the plasma insulin concentration (beta = 0.32, F =
      12.4, P < 0.001 and beta = 0.32, F = 13, P < 0.001, respectively), and
      haematocrit was found to be associated with DBP (beta = 0.21, F = 5.3, P < 0.05).
      In women, fasting insulins were unrelated to BP, but fasting plasma glucose and
      triglyceride concentrations and age were associated with SBP (beta = 0.29, F =
      15.5, P < 0.001, beta = 0.27, F = 14.3, P < 0.001, and beta = 0.2, F = 7.8, P <
      0.01, respectively), and haematocrit, fasting plasma glucose concentration and
      age were associated with DBP (beta = 0.29, F = 14, P < 0.001, beta = 0.2, F =
      6.9, P < 0.01 and beta = 0.2, F = 6.3, P < 0.05, respectively). These results
      suggest that the insulin-BP associations in healthy Japanese subjects over 60
      years of age differ according to sex, and that haematocrit is an important
      determinant of DBP in both sexes in our population.

PMID- 9249230
TI  - Metabolic and orthostatic blood pressure responses to a low-sodium diet in
      elderly hypertensives.
AB  - In view of the concern regarding the potential risks and benefits of sodium
      restriction, the effect on biochemical and orthostatic responses from a moderate
      reduction in sodium intake in elderly persons that is sufficient to lower
      systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged
      65-79 years entered a double-blind randomized placebo controlled cross-over trial
      of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium
      tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium
      periods, two 24-h urine collections and venous blood samples were undertaken and
      supine and standing BPs were recorded. On the low compared to the high sodium
      phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h,
      respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05)
      and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in
      total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate,
      parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion
      rate. Serum urate was significantly higher during the low compared to high sodium
      intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during
      the high and low sodium intakes were unchanged. In summary, after 5 weeks of
      moderate sodium restriction no adverse effects other than an increase in serum
      urate was seen in elderly hypertensive persons.

PMID- 9249231
TI  - Decreased cellular Mg2+ concentrations in a subgroup of hypertensives--cell
      models for the pathogenesis of primary hypertension.
AB  - A new method to determine total Mg2+ content in lymphocytes was developed,
      offering advantages for routine measurements as compared to fluorescence methods.
      Intracellular Mg2+ measurements were performed in lymphocytes of 18 untreated
      normotensive and 19 untreated essential hypertensive patients. Mg2+ content was
      referred to lymphocytic protein, which was determined according to Bradford's
      method. Mg2+ measurements were performed by atomic absorption spectroscopy using
      a Video 12 apparatus from Thermo Electron Instrumentation Laboratory, Andover,
      MA, USA. The results show that in patients with essential hypertension, total
      intralymphocytic Mg2+ content is significantly lower (0.07 +/- 0.05 mmol/g
      lymphocytic protein, mean +/- s.d.) as compared to controls (0.11 +/- 0.04 mmol/g
      lymphocytic protein, mean +/- s.d., P < 0.05). Free intracellular Mg2+ content
      was measured in lymphocytes by the fluorescent indicator mag-fura-II, showing no
      significant difference in normotensives and hypertensives (0.30 +/- 0.16 vs 0.38
      +/- 0.17 mmol/l). In platelets free intracellular Mg2+ concentrations were not
      found of significant difference in normotensive and hypertensive patients (0.52
      +/- 0.23 vs 0.47 +/- 0.27 mmol/l) using mag-fura-II. In plasma Mg2+
      concentrations there was no significant difference in the normotensive and
      hypertensive group (0.92 +/- 0.07 vs 0.88 to 0.07 mmol/l). There was no
      correlation between plasma, free or total cellular magnesium concentrations in
      each group. Furthermore this method also seems suitable for routine measurements
      of total intracellular Mg2+ concentrations in even larger groups of patients in
      comparison with fluorescent indicator measurements like mag-fura-II. Lowered
      total intracellular Mg2+ concentrations in a subgroup of primary hypertension may
      contribute to the development of this disorder, perhaps due to different
      buffering systems.

PMID- 9249232
TI  - Evaluation of plasma aldosterone to plasma renin activity ratio in patients with
      primary aldosteronism.
AB  - The plasma aldosterone to renin activity ratio (A/PRA) was assessed
      retrospectively in 103 patients with primary aldosteronism including 74 patients
      with surgically proven adrenal cortical adenoma (APA) and 29 patients with
      idiopathic adrenal cortical hyperplasia (IHA). The results were compared with
      those obtained in 31 patients with essential hypertension (EH) and 45 healthy
      normotensive controls. The upper limit of normal A/PRA ratio, as obtained in the
      controls was 17.8. This value was exceeded in 89% of patients with APA;
      postoperatively it decreased in 97% of the APA group, and returned to normal in
      81%. In the IHA group the A/PRA was elevated in 70% of patients. The normal
      ratios in patients with primary aldosteronism were associated with unsuppressed
      plasma renin activity (PRA). Although the mean values of the A/PRA ratio differed
      significantly between the groups, complete separation was not obtained. The serum
      potassium level at time of testing did not influence the diagnostic value of the
      A/PRA ratio, although an inverse correlation between serum potassium and the
      A/PRA ratio was found in the patients with APA. This study supports the high
      sensitivity of the A/PRA ratio in diagnosis of primary aldosteronism, however, a
      single determination with a normal result may not be sufficient for exclusion of
      the disease.

PMID- 9249233
TI  - Diltiazem slow-release and left-ventricular hypertrophy: a volumetric approach of
      left ventricular mass using magnetic resonance imaging.
AB  - AIMS: This study was designed to assess the changes in left ventricular mass
      (LVM) in hypertensive patients with left ventricular hypertrophy under drug
      therapy with once-daily slow-release diltiazem. Magnetic resonance imaging (MRI)
      was used for this purpose because of its higher reproducibility than M-mode or
      two-dimensional echocardiography. METHODS: Patients suffering from essential
      hypertension were included if their baseline LVM index (LVMI) was > or = 105 g/m2
      in male or > or = 85 g/m2 in female patients, ie, equal or higher to the median
      values observed in hypertensive patients in our institution. MRI consisted in a
      true short-axis, electrocardiogram (ECG) gated spin-echo slice acquisition at
      baseline, after 3 and 6 months of therapy (M0, M3, and M6). Data were stored on
      magnetic tapes and read subsequently under blind conditions and the control of an
      external auditor. RESULTS: Thirty-five patients were included. Of these, 14
      patients (40%) were not previously treated. Inter- and intra-observer variability
      for LVMI measurement were 5.6 +/- 4.3% and 2.1 +/- 3.0%, respectively. Mean
      baseline LVMI was 110 +/- 16 g/m2 in male and 96 +/- 16 g/m2 in female patients.
      It decreased by 3.6% at M3 (P = 0.05) and by 6.0% at M6 (P = 0.02). A trend
      towards a greater LVMI reduction was observed in previously untreated patients.
      CONCLUSION: This study confirms that MRI is a reproducible technique for the
      measurement of LVM. It demonstrates a significant reduction in LVMI as early as
      the 3rd month of therapy in hypertensive patients treated with once-daily
      sustained release (SR) diltiazem, although baseline LVMI in the majority of
      participating patients was only moderately increased.

PMID- 9249234
TI  - A randomised, double-blind trial comparing mibefradil and amlodipine: two long
      acting calcium antagonists with similar efficacy but different tolerability
      profiles. Mibefradil International Study Group.
AB  - OBJECTIVE: To compare the efficacy and tolerability of mibefradil and amlodipine
      in patients with uncomplicated mild-to-moderate essential hypertension. DESIGN: A
      double-blind, randomised, parallel group multicentre trial. METHODS: 239 patients
      received 50 mg mibefradil or 5 mg amlodipine for 4 weeks, followed by a forced
      titration to 100 mg mibefradil or 10 mg amlodipine for an additional 8 weeks.
      Patients then entered a 4-week withdrawal period either on therapy or switched to
      placebo. RESULTS: Statistically equivalent reductions in trough sitting diastolic
      blood pressure (SDBP) were observed after 12 weeks of once-daily treatment with
      50/100 mg mibefradil (-11.5 +/- 8.2 mm Hg) and 5/10 mg amlodipine (-13.2 +/- 7.9
      mm Hg). The number of patients with normalised SDBP (< or = 90 mm Hg) increased
      23.3% in the mibefradil group and 19.5% in the amlodipine group (approximately
      74% in both groups). Patients on mibefradil or amlodipine during the withdrawal
      period had significantly larger decreases in SDBP than those on placebo. Patients
      on mibefradil had a decrease in heart rate of 5.5 bpm. Patients on amlodipine had
      no change in heart rate; however, cessation of amlodipine was associated with a
      decrease in heart rate. CONCLUSIONS: Mibefradil was as effective as amlodipine in
      reducing BP; both compounds were effective treatments of hypertension.

PMID- 9249235
TI  - Fundal changes in malignant hypertension.

PMID- 9249236
TI  - In vivo evidence for B1-receptor synthesis induction by heat stress in the rat.
AB  - A hypotensive effect of intravenously injected [des-Arg9]-bradykinin was found in
      Wistar rats following acute heat stress. This effect was similar to that of
      intravenously injected bradykinin and was observed 6, 18 and 24 h following an
      increase in rectal temperature at 42 degrees C for 20 min (H6, H18 and H24
      groups, respectively). In contrast, [des-Arg9-bradykinin had no effect on blood
      pressure in control or sham conditions, early on (3 h) or later on (72 h) after
      heat stress (Ctl, H3 and H72 groups, respectively), while the response to
      bradykinin was maintained. The hypotension induced by [des-Arg9]-bradykinin in
      groups H6, H18 and H24 was comparable to that induced in rats pretreated with a
      small amount of endotoxin 24 h earlier (LPS group). The hypotensive response in
      group H24 was totally blunted by [des-Arg10]-Hoe 140 (a potent B1 receptor
      antagonist) infused at a rate of 10 microg min(-1). These results suggest that
      heat stress induces the synthesis of vascular B1 receptors in the rat.

PMID- 9249237
TI  - Neocuproine, a selective Cu(I) chelator, and the relaxation of rat vascular
      smooth muscle by S-nitrosothiols.
AB  - 1. A study has been made of the effect of neocuproine, a specific Cu(I) chelator,
      on vasodilator responses of rat isolated perfused tail artery to two
      nitrosothiols: S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and S-nitroso
      glutathione (GSNO). 2. Bolus injections (10 microl) of SNAP or GSNO (10(-7)-10(
      3) M) were delivered into the lumen of perfused vessels pre-contracted with
      sufficient phenylephrine (1-7 microM) to develop pressures of 100-120 mmHg. Two
      kinds of experiment were made: SNAP and GSNO were either (a) pre-mixed with
      neocuproine (10(-4) M) and then injected into arteries; or (b) vessels were
      continuously perfused with neocuproine (10(-5) M) and then injected with either
      pure SNAP or GSNO. 3. In each case, neocuproine significantly attenuated
      vasodilator responses to both nitrosothiols, although the nature of the
      inhibitory effect differed in the two types of experiment. We conclude that the
      ability of exogenous nitrosothiols to relax vascular smooth muscle in our ex vivo
      model is dependent upon a Cu(I) catalyzed process. Evidence is presented which
      suggests that a similar Cu(I)-dependent mechanism is responsible for the release
      of NO from endogenous nitrosothiols and that this process may assist in
      maintaining vasodilator tone in vivo.

PMID- 9249238
TI  - Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the
      basilar artery from Wistar Kyoto and stroke-prone rats.
AB  - 1. Isolated basilar arteries from spontaneously hypertensive stroke-prone rats
      (SHRSP) are more sensitive to the contractile effect of 5-hydroxytryptamine (5
      HT) than those from normotensive Wistar Kyoto rats (WKY). This has been
      attributed to a different proportion of 5-HT receptor subtypes mediating these
      responses. In the present study we have examined if differences in nitric oxide
      release could also contribute to this difference in sensitivity to 5-HT. 2. At
      rest, the normalized internal diameter was significantly smaller in SHRSP (297.4
      +/- 3.5 microm, n = 88) than in WKY (375.1 +/- 4.0 microm, n = 62, P<0.01)
      arteries. The contractile response to 100 mM KCl was higher in WKY (3.57 +/- 0.15
      mN mm(-1), n = 22) than in SHRSP arteries (2.32 +/- 0.20 mN mm(-1), n = 28,
      P<0.01). 3. When added on the plateau of contraction to 5-HT (1 microM),
      acetylcholine (ACh, 3 microM) evoked significant relaxation in all preparations
      from WKY (n = 20), but only in 15 out of 26 preparations from SHRSP. The mean
      relaxations were 55.4 +/- 5.2% in WKY and 20.6 +/- 4.6% in SHRSP (as % of the
      contractile tone evoked by 5-HT: P<0.01). 4. The NO synthase inhibitor N(omega)
      nitro-L-arginine (L-NOARG, 0.1 mM) produced a similar increase in tone in both
      WKY and SHRSP. This tone was equal (in % of the contractile response to 100 mM
      KCl) to 70.8 +/- 4.4% in WKY (n = 20) and 67.6 +/- 5.9% in SHRSP (n=26) and was
      reversed by L-arginine (1 mM) and by 1,4-dihydropyridine calcium channel blockers
      (10 nM nisoldipine, 10 nM lacidipine, 100 nM nifedipine). The L-NOARG-induced
      tone was absent when the arteries were bathed in phosphate-free Krebs (pH 7.4).
      5. EC50 values of 5-HT were about four fold smaller in SHRSP than in WKY arteries
      (P<0.01). The maximal response to 5-HT (Emax) was higher than 100 mM KCl
      contraction in SHRSP but not in WKY arteries. Removal of endothelium produced a
      shift to the left of the 5-HT curve in WKY, but not in SHRSP arteries. 6. When
      evoked in phosphate-free Krebs, the contractile responses to 5-HT showed
      tachyphylaxis, but the responses were reproducible by adding the agonist at 30
      min intervals. In such conditions, EC50 values of 5-HT were about two fold
      smaller in SHRSP than in WKY arteries (P<0.01). In phosphate-free Krebs, the
      blockade of NO synthase did not change the contractile response to 100 mM KCl; it
      reduced EC50 and increased Emax of 5-HT in WKY, but not in SHRSP. 7. These
      results confirm that the sensitivity to 5-HT is higher in basilar artery isolated
      from SHRSP than in those from WKY. They show that endothelium-dependent
      vasorelaxation to ACh is impaired in SHRSP. The finding that removal of
      endothelium or blockade of NO synthase augmented the contractile response to 5-HT
      in WKY, but not in SHRSP basilar arteries indicates that the difference in
      responsiveness to 5-HT observed between WKY and SHRSP basilar arteries might be,
      at least in part, related to dissimilarities in NO release. Furthermore, the L
      NOARG-induced contraction sensitive to calcium channel blockers indicates that,
      in basilar arteries, NO production might lower L-type calcium channel opening and
      thereby control the tone of the vessels.

PMID- 9249239
TI  - Differential contribution of two serine residues of wild type and constitutively
      active beta2-adrenoceptors to the interaction with beta2-selective agonists.
AB  - 1. We have studied the difference in receptor binding activity between partial
      and full beta2-adrenoceptor agonists and the abilities of the agonists to
      interact with Ser204 and Ser207 in the fifth transmembrane region of the beta2
      adrenoceptor, amino acid residues that are important for activation of the beta2
      adrenoceptor. 2. In the binding study with [125I]-iodocyanopindolol, the Ki
      values of (+/-)-salbutamol, (+/-)-salmeterol, TA-2005 and (-)-isoprenaline for
      the beta2-adrenoceptor expressed in COS-7 cell membranes were 3340, 21.0, 12.0
      and 904 nM, respectively. The beta1/beta2 selectivity of these agonists was in
      the order of (+/-)-salmeterol (332 fold) > TA-2005 (52.8) > (+/-)-salbutamol
      (6.8) > (-)-isoprenaline (1.1), and the beta3-/beta2-adrenoceptor selectivity of
      these agonists was in the order of TA-2005 (150 fold) > (+/-)-salmeterol (88.6) >
      (+/-)-salbutamol (10.4) > (-)-isoprenaline (3.2). 3. The maximal activation of
      adenylyl cyclase by stimulation of the beta1-, beta2- and beta3-adrenoceptors by
      TA-2005 was 32, 100 and 100% of that by (-)-isoprenaline, respectively,
      indicating that TA-2005 is a full agonist at the beta2- and beta3-adrenoceptors
      and a partial agonist at the beta1-adrenoceptor. (+/-)-Salbutamol and (+/-)
      salmeterol were partial agonists at both beta1- (8% and 9% of (-)-isoprenaline)
      and beta2- (83% and 74% of (-)-isoprenaline) adrenoceptors. 4. The affinities of
      full agonists, TA-2005 and (-)-isoprenaline, were markedly decreased by
      substitution of Ala for Ser204 (S204A) of the beta2-adrenoceptor, whereas this
      substitution slightly reduced the affinities of partial agonists, (+/-)
      salbutamol and (+/-)-salmeterol. Although the affinities of full agonists for the
      S207A-beta2-adrenoceptor were decreased, those of partial agonists for the S207A
      beta2-adrenoceptor were essentially the same as for the wild type receptor. 5.
      The constitutively active mutant (L266S, L272A) of the beta2-adrenoceptor had an
      increased affinity for all four agonists. The affinities of full agonists were
      decreased by substitution of Ser204 of the constitutively active mutant, whereas
      the degree of decrease was smaller than that caused by the substitution of the
      wild type receptor. Although the affinities of (+/-)-salbutamol and (+/-)
      salmeterol for the S207A-beta2-adrenoceptor were essentially the same as those
      for the wild type beta2-adrenoceptor, the affinities of (+/-)-salbutamol and (+/
      )-salmeterol for the constitutively active beta2-adrenoceptor were decreased by
      substitution of Ser207. 6. These results suggest that Ser204 and Ser207 of the
      wild type and constitutively active beta2-adrenoceptors differentially interacted
      with beta2-selective agonists.

PMID- 9249240
TI  - Beneficial effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose)
      synthetase in a rat model of splanchnic artery occlusion and reperfusion.
AB  - 1. Peroxynitrite, a potent cytotoxic oxidant formed by the reaction of nitric
      oxide with superoxide anion, and hydroxyl radical, formed in the iron-catalysed
      Fenton reaction, are important mediators of reperfusion injury. In in vitro
      studies, DNA single strand breakage, triggered by peroxynitrite or by hydroxyl
      radical, activates the nuclear enzyme poly (ADP-ribose) synthetase (PARS), with
      consequent cytotoxic effects. Using 3-aminobenzamide, an inhibitor of PARS, we
      investigated the role of PARS in the pathogenesis of splanchnic artery occlusion
      shock. 2. Splanchnic artery occlusion and reperfusion shock (SAO/R) was induced
      in rats by clamping both the superior mesenteric artery and the coeliac trunk for
      45 min, followed by release of the clamp (reperfusion). At 60 min after
      reperfusion, animals were killed for histological examination and biochemical
      studies. 3. SAO/R rats developed a significant fall in mean arterial blood
      pressure, significant increase of tissue myeloperoxidase activity and marked
      histological injury to the distal ileum. SAO/R was also associated with a
      significant mortality (0% survival at 2 h after reperfusion). 4. There was a
      marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker
      of peroxynitrite-induced oxidative processes) in the plasma of the SAO/R rats,
      starting early after reperfusion, but not during ischaemia alone.
      Immunohistochemical examination demonstrated a marked increase in the
      immunoreactivity to nitrotyrosine, a specific 'footprint' of peroxynitrite, in
      the necrotic ileum in shocked rats, as measured at 60 min after the start of
      reperfusion. 5. In addition, in ex vivo studies in aortic rings from shocked
      rats, we found reduced contractions to noradrenaline and reduced responsiveness
      to a relaxant effect to acetylcholine (vascular hyporeactivity and endothelial
      dysfunction, respectively). 6. In a separate set of studies, using a 4000 Dalton
      fluorescent dextran tracer, we investigated the changes in epithelial
      permeability associated with SAO/R. Ten minutes of reperfusion, after 30 min of
      splanchnic artery ischaemia, resulted in a marked increase in epithelial
      permeability. 7. There was a significant increase in PARS activity in the
      intestinal epithelial cells, as measured 10 min after reperfusion ex vivo. 3
      Aminobenzamide, a pharmacological inhibitor of PARS (applied at 10 mg kg(-1),
      i.v., 5 min before reperfusion, followed by an infusion of 10 mg kg(-1) h(-1)),
      significantly reduced ischaemia/reperfusion injury in the bowel, as evaluated by
      histological examination. Also it significantly improved mean arterial blood
      pressure, improved contractile responsiveness to noradrenaline, enhanced the
      endothelium-dependent relaxations and reduced the reperfusion-induced increase in
      epithelial permeability. 8. 3-Aminobenzamide also prevented the infiltration of
      neutrophils into the reperfused intestine, as evidenced by reduced
      myeloperoxidase activity. It improved the histological status of the reperfused
      tissues, reduced the production of peroxynitrite in the late phase of reperfusion
      and improved survival. 9. In conclusion, our study demonstrates that the PARS
      inhibitor 3-aminobenzamide exerts multiple protective effects in splanchnic
      artery occlusion/reperfusion shock. We suggest that peroxynitrite and/or hydroxyl
      radical, produced during the reperfusion phase, trigger DNA strand breakage, PARS
      activation and subsequent cellular dysfunction. The vascular endothelium is
      likely to represent an important cellular site of protection by 3-aminobenzamide
      in SAO shock.

PMID- 9249241
TI  - Modulation of synovial blood flow by the calcitonin gene-related peptide (CGRP)
      receptor antagonist, CGRP(8-37).
AB  - 1. The effect of the calcitonin gene-related peptide (CGRP) receptor antagonist,
      CGRP(8-37) on blood flow in the knee joint of the anaesthetized rat was
      investigated. 2. Synovial blood flow in both exposed and intact, skin-covered
      knees was measured by laser Doppler perfusion imaging. 3. Topical application of
      CGRP(8-37) caused a dose-dependent fall in synovial blood flow in the exposed
      knee joint of the rat. At low (1.5 nmol) doses of CGRP(8-37) there was no
      significant effect on synovial blood flow. In rats treated with 7.5 nmol CGRP(8
      37) there was a fall in synovial blood flow (maximum effect at 10 min: -28.8 +/-
      4.6%; n=7), which returned to resting levels within 30 min. The highest dose (15
      nmol) of antagonist used in this study caused a marked (maximum at 10 min: -35.6
      +/- 9.3%; n=8), and prolonged (up to 30 min) fall in blood flow. 4. Ten days
      after surgical denervation, CGRP(9-37) (15 nmol, topical) had no significant
      effect on blood flow in the rat exposed knee joint (change in flux at 10 min: 
      5.1+/-3.6%; n=4). This suggests that CGRP(8-37) acts selectively to antagonize
      the actions of a neurally derived product, probably CGRP, on the rat synovial
      vasculature. 5. In skin-covered knee joints, intra-articular injection of CGRP(8
      37) (15 nmol; bolus) elicited a significant fall in synovial blood flow (maximum
      effect at 10 min: -15.5 +/- 5.8%; n=6). 6. CGRP (0.01, 0.1 or 1.0 nmol; topical)
      caused a dose-dependent increase in exposed knee joint blood flow, which was
      attenuated by co-administration of 1.5 nmol CGRP(8-37). For example, 1 nmol CGRP
      elicited a peak increase in flux at 10 min of 94.7 +/- 31.8% (n=8) and 28.8 +/-
      8.9% (n=7) in the absence and presence of CGRP(8-37), respectively. The
      vasodilator responses induced by acetylcholine (ACh) (10 nmol, topical; n=4-5) or
      sodium nitroprusside (SNP) (10 nmol, topical; n=4-5) were unaltered in the
      presence of CGRP(8-37) (1.5 nmol, topical). 7. Thus, the CGRP receptor antagonist
      CGRP(8-37) elicits vasoconstriction in the rat synovium. This suggests that the
      endogenous, basal release of CGRP may play a physiological role in the regulation
      of blood flow in the rat knee joint.

PMID- 9249242
TI  - Characterization of angiotensin II formation in human isolated bladder by
      selective inhibitors of ACE and human chymase: a functional and biochemical
      study.
AB  - 1. Functional recordings of smooth muscle tension and biochemical experiments on
      membrane fractions were performed to characterize angiotensin II (AII) formation
      in human isolated bladder smooth muscle. 2. A novel human chymase inhibitor CH
      5450 (Z-Ile-Glu-Pro-Phe-CO2Me) and a recently developed human chymase substrate
      Pro11-,D-Ala12)-angiotensin I, claimed to be resistant to angiotensin converting
      enzyme (ACE) and carboxypeptidase, were used. 3. Angiotensin I (AI) (0.3 microM)
      induced a contractile response amounting to 58 +/- 5% (n=12) of the initial K+
      (124 mM)-induced contractions. This response was reduced to 36 +/- 3% (n=8) by
      the ACE-inhibitor enalaprilat (10 microM), while pretreatment with soybean
      trypsin inhibitor (STI 200 microg ml(-1)) or CH 5450 (10 microM) had no effect.
      However, the combination of enalaprilat and STI reduced the AI-induced
      contractions to 19 +/- 5% (n=6), and the combination of enalaprilat and CH 5450
      caused an almost complete inhibition of the AI-induced contractions to 1+/-1%
      (n=6). 4. The substrate (Pro11-,D-Ala12)-AI (3 microM) produced contractions
      which amounted to 57 +/- 4% (n=13) of the initial K+ (124 mM) contractions. These
      contractions were not affected by enalaprilat (10 microM). On the other hand, STI
      (200 microg ml(-1)) and CH 5450 (10 microM) added separately, depressed the
      (Pro11-,D-Ala12)-AI-induced contractions to 34 +/- 5% (n=6) and 24 +/- 4% (n=6),
      respectively. The combination of enalaprilat and STI or enalaprilat and CH 5450
      did not produce any further inhibition. 5. Experiments with detrusor membrane
      fractions incubated with AI (50 microM) were performed. In the presence of
      enalaprilat (100 microM), carboxypeptidase inhibitor CPI (10 microg ml(-1)) and
      aprotinin (15 microM), CH 5450 (10 nM-1 microM) caused a concentration-dependent
      inhibition of AII formation. 6. The results confirm that AII is a potent
      contractile agent in the human isolated detrusor muscle. They also indicate that
      the serine protease responsible for AII formation in the human bladder in vitro
      is human chymase or an enzyme similar to human chymase.

PMID- 9249243
TI  - Coexistence of purino- and pyrimidinoceptors on activated rat microglial cells.
AB  - 1. Nucleotide-induced currents in untreated (proliferating) and
      lipopolysaccharide (LPS; 100 ng ml(-1)) treated (non-proliferating) rat
      microglial cells were recorded by the whole-cell patch-clamp technique. Most
      experiments were carried out on non-proliferating microglial cells. ATP (100 nM-1
      mM), ADP (10 nM-10 mM) and UTP (1 microM-100 mM), but not uridine (100 microM-10
      mM) produced a slow outward current at a holding potential of 0 mV. The effect of
      UTP (1 mM) did not depend on the presence of extracellular Mg2+ (1 mM). The
      outward current response to UTP (1 mM) was similar in non-proliferating and
      proliferating microglia. 2. In non-proliferating microglial cells, the ATP (10
      microM)-induced outward current was antagonized by suramin (300 microM) or
      reactive blue 2 (50 microM), whereas 8-(p-sulphophenyl)-theophylline (8-SPT; 100
      microM) was inactive. By contrast, the current induced by UTP (1 mM) was
      increased by suramin (300 microM) and was not altered by reactive blue 2 (50
      microM) or 8-SPT (100 microM). 3. The current response to UTP (1 mM) disappeared
      when K+ was replaced in the pipette solution by an equimolar concentration of Cs+
      (150 mM). However, the effect of UTP (1 mM) did not change when most Cl- was
      replaced with an equimolar concentration of gluconate (145 mM). The application
      of 4-aminopyridine (1 mM) or Cs+ (1 mM) to the bath solution failed to alter the
      UTP (1 mM)-induced current. UTP (1 mM) had almost no effect in a nominally Ca2+
      free bath medium, or in the presence of charybdotoxin (0.1 microM); the inclusion
      of U-73122 (5 microM) or heparin (5 mg ml(-1)) into the pipette solution also
      blocked the responses to UTP (1 mM). By contrast, the effect of ATP (10 microM)
      persisted under these conditions. 4. I-V relations were determined by delivering
      fast voltage ramps before and during the application of UTP (1 mM). In the
      presence of extracellular Cs+ (1 mM) and 4-aminopyridine (1 mM) the UTP-evoked
      current crossed the zero current level near -75 mV. Omission of Ca2+ from the Cs+
      (1 mM)- and 4-aminopyridine (1 mM)-containing bath medium or replacement of K+ by
      Cs+ (150 mM) in the pipette solution abolished the UTP current. 5. Replacement of
      GTP (200 microM) by GDP-beta-S (200 microM) in the pipette solution abolished the
      current evoked by UTP (1 mM). 6. When the pipette solution contained Cs+ (150 mM)
      instead of K+ and in addition inositol 1,4,5,-trisphosphate (InsP3; 10 microM),
      an inward current absolutely dependent on extracellular Ca2+ was activated after
      the establishment of whole-cell recording conditions. This current had a typical
      delay, a rather slow time course and did not reverse its amplitude up to 100 mV,
      as measured by fast voltage ramps. 7. A rise of the internal free Ca2+
      concentration from 0.01 to 0.5 microM on excised inside-out membrane patches
      produced single channel activity with a reversal potential of 0 mV in a
      symmetrical K+ solution. The reversal potential was shifted to negative values,
      when the extracellular K+ concentration was decreased from 144 to 32 mM. By
      contrast, a decrease of the extracellular Cl- concentration from 164 to 38 mM did
      not change the reversal potential. 8. Purine and pyrimidine nucleotides act at
      separate receptors in rat microglial cells. Pyrimidinoceptors activate via a G
      protein the enzyme phospholipase C with the subsequent release of InsP3. The
      depletion of the intracellular Ca2+ pool appears to initiate a capacitative entry
      of Ca+ from the extracellular space. This Ca2+ then activates a Ca2+-dependent K+
      current.

PMID- 9249244
TI  - Inherent tone of human bronchus: role of eicosanoids and the epithelium.
AB  - 1. Airway preparations of different species possess varying degrees of inherent
      tone which is the result of different metabolites of arachidonic acid in
      different species. In human bronchial smooth muscle in vitro we have investigated
      the effects of 5-lipoxygenase inhibition (zileuton, 10 microM), cyclo-oxygenase
      inhibition (indomethacin, 1 microM) and mechanical epithelium removal on inherent
      tone. The shunting of arachidonic acid by inhibition of one or other of these
      enzymes, as a possible explanation for the effects observed, has also been
      investigated. 2. Zileuton caused a significant fall in tone either alone (-107 +/
      33 mg) or after cyclo-oxygenase inhibition (-203 +/- 48 mg) and this effect was
      not significantly altered by epithelial removal (-191 +/- 43 mg alone; -333 +/-
      88 mg after indomethacin). Indomethacin increased tone when applied alone (160 +/
      94 mg), but this effect only reached statistical significance after 5
      lipoxygenase inhibition, (210+/-81 mg; P<0.05). Epithelial removal did not alter
      the effect of indomethacin when applied alone (213+/-97 mg), but significantly
      reduced the effect of indomethacin after 5-lipoxygenase inhibition (34 +/- 23 mg;
      P<0.05). 3. These data suggest that inherent tone in human bronchus is largely
      the result of contractile 5-lipoxygenase products. However, the involvement of
      cyclo-oxygenase products cannot entirely be discounted, since in the presence of
      5-lipoxygenase inhibition contractile and relaxant eicosanoids originating from
      the bronchial epithelium appear to influence significantly inherent tone.

PMID- 9249246
TI  - Signalling pathways in bradykinin- and nitric oxide-induced hypotension in the
      normotensive rat; role of K+-channels.
AB  - 1. Bradykinin and nitric oxide (NO) are potent hypotensive agents. In the present
      study, the role of K+-channels in the signalling pathways responsible for their
      hypotensive action was investigated in normotensive, anaesthetized rats. The rats
      were treated with ion-channel inhibitors before administration of bradykinin
      (2.8, 5.6, 28 and 56 nmol kg(-1), i.v.) followed in some of the protocols by
      nitroprusside (1.1, 3.5, 7, 14, and 28 nmol kg(-1), i.v.). 2. No attenuation of
      the hypotensive response to bradykinin was detected for inhibitors of the Na-K-Cl
      cotransporter (30 micromol kg(-1) furosemide), the ATP-sensitive K+-channel (40
      micromol kg(-1) glibenclamide), high conductance Ca2+-activated K+-channel (180
      micromol kg(-1) tetraethylammonium, 54 micromol kg(-1) tetrabutylammonium, 35
      nmol kg(-1) iberiotoxin, 35 nmol kg(-1) charybdotoxin) or the low conductance
      Ca2+-activated K+-channel (74 nmol kg(-1) apamin). 3. However, the voltage
      sensitive K+-channel (I(A)) inhibitor 4-aminopyridine (4.05-40.5 micromol kg(-1))
      induced a concentration-dependent (P<0.0001) attenuation of the hypotensive
      response (P<0.0001). Bradykinin had no effect on heart rate in anaesthetized rats
      and this observation was not altered by pretreatment with 4-aminopyridine. 4. 4
      Aminopyridine (53 micromol kg(-1)) also significantly attenuated the hypotensive
      response to nitroprusside (P<0.0003) without altering the heart rate
      concentration-response curve. Of the two Ca2+-activated K+-channel inhibitors
      tested on nitroprusside-induced hypotension, tetrabutylammonium induced a slight
      attenuation (P<0.0101), whereas iberiotoxin had no effect. 5. We therefore
      concluded that, although the acute hypotensive response to bradykinin in the
      normotensive rat is not mediated through nitric oxide synthesis, the hypotensive
      response to both agents was mediated through opening of voltage-sensitive K+
      channels (I(A)), resulting in a decrease in peripheral vascular resistance.

PMID- 9249245
TI  - Involvement of vasoactive intestinal polypeptide in nicotine-induced relaxation
      of the rat gastric fundus.
AB  - 1. Nicotine-induced relaxation and release of vasoactive intestinal polypeptide
      (VIP)- and peptide histidine isoleucine (PHI)-like immunoreactivity (LI) were
      measured in longitudinal muscle strips from the rat gastric fundus. 2. Under non
      cholinergic conditions (0.3 microM atropine), nicotine (3-300 microM) produced
      concentration-dependent relaxations of the 5-hydroxytryptamine (3 microM)
      precontracted strips. Under non-adrenergic non-cholinergic (NANC) conditions (0.3
      microM atropine + 1 microM phentolamine + 1 microM nadolol), relaxations induced
      by sub-maximal nicotine concentrations (10 and 30 microM) were significantly
      smaller, while that produced by the highest concentration used (300 microM) was
      similar to that seen under non-cholinergic conditions. 3. Re-exposure to the same
      nicotine concentration 1 h later induced smaller relaxations, indicating
      desensitization. The reductions seen in the second responses were proportional to
      the concentration used. 4. Under non-cholinergic conditions, the relaxant
      response to 30 microM nicotine was abolished by hexamethonium (100 microM) and
      significantly reduced by tetrodotoxin (TTX, 3 microM). The TTX-resistant
      component was not observed under NANC conditions. 5. NANC relaxation induced by
      30 microM nicotine was significantly reduced by a specific anti-VIP serum
      (approximately 35% less than that seen with normal rabbit serum). 6. Nicotine (30
      300 microM) caused significant, concentration-dependent increases in the outflow
      of VIP- and PHI-LI from the strips; these effects were also diminished with re
      exposure. The increases in both types of immunoreactivity evoked by nicotine (300
      microM) were abolished by hexamethonium (300 microM), TTX (3 microM) and a
      calcium-free medium. 7. These findings indicate that VIP and possibly PHI are
      involved in NANC relaxation of the rat gastric fundus induced by nicotine.

PMID- 9249247
TI  - Characterization of P2 receptors for purine and pyrimidine nucleotides in human
      placental cotyledons.
AB  - 1. The aim of this study was to characterize P2 receptors in the arterial
      vascular bed of human perfused placental cotyledons. Vasoconstrictor responses to
      bolus injections of purine and pyrimidine nucleotides were tested at basal tone,
      and vasodilator responses in preparations with tone raised by perfusion with
      prostaglandin F2alpha (PGF2alpha; 10-50 nM). 2. At basal tone, bolus injections
      of the P2X-selective agonist alpha,beta-methylene ATP (alpha,beta-meATP; 0.5-500
      nmol) elicited dose-dependent vasoconstriction. ATP (0.005-5 micromol) also
      elicited dose-dependent vasoconstriction, but was less potent than alpha,beta
      meATP. Vasoconstriction was also elicited by other nucleotides, but only at the
      highest dose tested (5 micromol): UTP > CTP = ITP (n = 6). GTP and TTP did not
      cause vasoconstriction. 3. Constrictor responses to bolus injections of
      alpha,beta-meATP were resistant to desensitization and were not significantly
      affected when carried out in the presence of 1 microM alpha,beta-meATP added to
      the perfusate. However, responses to bolus injections of alpha,beta-meATP were
      partially blocked by perfusion with 10 microM alpha,beta-meATP. In contrast,
      responses to ATP and UTP were unaffected by 10 microM alpha,beta-meATP. The P2X
      receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS;
      10 and 100 microM) had no significant effect on vasoconstriction mediated by
      alpha,beta-meATP and ATP. 4. Removal of the endothelium had no significant effect
      on constrictor responses to alpha,beta-meATP, ATP and UTP. Inhibition of nitric
      oxide (NO) synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM)
      had no significant effect on vasoconstriction to ATP and alpha,beta-meATP. 5. In
      preparations with tone raised with PGF2alpha (10-50 nM) vasodilatation was
      elicited by nucleotides with the following order of potency: 2MeSATP = ADP >> ATP
      > UTP > CTP = GTP = ITP = TTP. pD2 values were: 2MeSATP, 10.03+/-0.26 (n=7); ADP,
      9.97+/-0.40 (n=5); ATP, 8.89+/-0.18 (n=7); UTP, 7.79+/-0.35 (n=7). Maximal
      responses to 2MeSATP and ADP were similar and were approximately 40% greater than
      maximal responses to ATP and UTP. 6. Vasodilator responses to nucleotides were
      abolished by L-NAME (100 microM) and by removal of the endothelium. 7. In
      conclusion, contractile responses mediated by alpha,beta-meATP and ATP in human
      placental smooth muscle are resistant to desensitization and insensitive to PPADS
      and, thus, show a dissimilar pharmacological profile to the classic smooth muscle
      P2X1 receptor. There may be two subtypes of smooth muscle P2 receptor based on
      differential antagonism of alpha,beta-meATP and ATP with alpha,beta-meATP. A
      smooth muscle P2 receptor mediates vasoconstriction to UTP, and may indicate a
      further subtype. Endothelium-dependent, NO-dependent, vasodilatation to 2MeSATP
      and ADP may be mediated by P2Y1 receptors, while endothelial P2Y2 receptors are
      likely to mediate NO-dependent relaxation to ATP and UTP.

PMID- 9249248
TI  - Pharmacological pleiotropism of the human recombinant alpha1A-adrenoceptor:
      implications for alpha1-adrenoceptor classification.
AB  - 1. Three fully-defined alpha1-adrenoceptors (alpha1A, alpha1B and alpha1D) have
      been established in pharmacological and molecular studies. A fourth alpha1
      adrenoceptor, the putative alpha1L-adrenoceptor, has been defined in functional
      but not molecular studies, and has been proposed to mediate contraction of human
      lower urinary tract tissues; its relationship to the three fully characterized
      alpha1-adrenoceptors is not known. 2. In the present study, binding affinities
      were estimated by displacement of [3H]-prazosin in membrane homogenates of
      Chinese hamster ovary (CHO-K1) cells stably expressing the human alpha1A-,
      alpha1B- and alpha1D-adrenoceptors and were compared with affinity estimates
      obtained functionally in identical cells by measuring inhibition of noradrenaline
      (NA)-stimulated accumulation of [3H]-inositol phosphates. 3. For the alpha1A
      adrenoceptor, binding studies revealed a pharmacological profile typical for the
      classically defined alpha1A-adrenoceptor, such that prazosin, RS-17053, WB 4101,
      5-methylurapidil, Rec 15/2739 and S-niguldipine all displayed subnanomolar
      affinity. A different profile of affinity estimates was obtained in inositol
      phosphates accumulation studies: prazosin, WB 4101, 5-methylurapidil, RS-17053
      and S-niguldipine showed 10 to 40 fold lower affinity than in membrane binding.
      However, affinity estimates were not 'frameshifted', as tamsulosin, indoramin and
      Rec 15/2739 yielded similar, high affinity estimates in binding and functional
      assays. 4. In contrast, results from human alpha1B- and alpha1D-adrenoceptors
      expressed in CHO-K1 cells gave antagonist affinity profiles in binding and
      functional assays that were essentially identical. 5. A concordance of affinity
      estimates from the functional (inositol phosphates accumulation) studies of the
      alpha1A-adrenoceptor in CHO-K1 cells was found with estimates published recently
      from contractile studies in human lower urinary tract tissues (putative alpha1L
      adrenoceptor). These data show that upon functional pharmacological analysis, the
      cloned alpha1A-adrenoceptor displays pharmacological recognition properties
      consistent with those of the putative alpha1L-adrenoceptor. Why this profile
      differs from that obtained in membrane binding, and whether it explains the
      alpha1L-adrenoceptor pharmacology observed in many native tissues, requires
      further investigation.

PMID- 9249249
TI  - Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine.
AB  - 1. Two types of Ca2+ channel alpha1-subunits were co-expressed in Xenopus oocytes
      with the Ca2+ channel alpha2- and beta1-subunits. The Ba2+ current through the
      alpha1C alpha2beta and the alpha1B alpha2beta channels had electrophysiological
      and pharmacological properties of L- and N-type Ca2+ channels, respectively. 2.
      Amlodipine had a strong blocking action on both the L-type and N-type Ca2+
      channels expressed in the oocyte. The potency of the amlodipine block on the N
      type Ca2+ channel was comparable to that on the L-type Ca2+ channel. At -100 mV
      holding potential, the IC50 values for amlodipine block on the L-type and N-type
      Ca2+ channel were 2.4 and 5.8 microM, respectively. 3. The blocking action of
      amlodipine on the N-type Ca2+ channel was dependent on holding potential and
      extracellular pH, as has been observed with amlodipine block on the L-type Ca2+
      channel. A depolarized holding potential and high pH enhanced the blocking action
      of amlodipine. 4. The time course of block development by amlodipine was similar
      for L-type and N-type Ca2+ channels. However, it was slower than the time course
      of block development by nifedipine for the L-type Ca2+ channel.

PMID- 9249250
TI  - Renal effects of intrathecally injected tachykinins in the conscious saline
      loaded rat: receptor and mechanism of action.
AB  - 1. The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A
      (NKA), [beta-Ala8]NKA (4-10) and [MePhe7]neurokinin B (NKB) at T13 thoracic
      spinal cord level were investigated on renal excretion of water, sodium and
      potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP
      67580), NK2 (SR 48968) and NK3 (R 820; 3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl)
      receptors were used to characterize the spinal effect of SP on renal function. 2.
      Saline gavage (4.5% of the body weight) enhanced renal excretion of water, sodium
      and potassium over the subsequent hour of measurement. Whereas these renal
      responses were not affected by 0.65 nmol SP, the dose of 6.5 nmol SP blocked the
      natriuretic response (aCSF value 3.9 +/- 0.8; SP value 0.7 +/- 0.3 micromol min(
      1), P<0.01) as well as the renal excretion of water (aCSF value 48.9 +/- 5.8; SP
      value 14.5 +/- 4.0 microl min(-1), P<0.01) and potassium (aCSF value 4.8 +/- 0.6;
      SP value 1.5 +/- 0.6 micromol min(-1), P<0.01) at 30 min post-injection. SP had
      no significant effect on urinary osmolality. The SP-induced renal inhibitory
      effects during the first 30 min were abolished in rats subjected to bilateral
      renal denervation 1 week earlier or in rats injected i.t. 5 min earlier with 6.5
      nmol RP 67580. In contrast, the co-injection of SR 48968 and R 820 (6.5 nmol
      each) did not affect the inhibitory responses to SP. On their own, these
      antagonists had no direct effect on renal excretion function. Since SP induced
      only transient changes in mean arterial blood pressure (-18.8 +/- 3.8 mmHg at 1
      min and +6.3 +/- 2.4 mmHg at 5 min post-injection), it is unlikely that the renal
      effects of SP are due to systemic haemodynamic changes. 3. NKA (6.5 nmol but not
      0.65 nmol) produced a transient drop in renal excretion of water (aCSF value 31.2
      +/- 5.1; NKA value 11.3 +/- 4.2 microl min(-1), P<0.05), sodium (aCSF value 1.7
      +/- 0.8; NKA value 0.4 +/- 0.2 micromol min(-1), P<0.05) and potassium (aCSF
      value 4.1 +/- 0.7; NKA value 1.5 +/- 0.4 micromol min(-1), P<0.05) at 15 min post
      injection. However, the same doses (6.5 nmol) of selective agonists for
      tachykinin NK2 ([beta-Ala8]NKA(4-10)) and NK3 ([MePhe7]NKB) receptors were devoid
      of renal effects. 4. This study provided functional evidence that tachykinins may
      be involved in the renal control of water and electrolyte excretion at the level
      of the rat spinal cord through the activation of NK1 receptors and the
      sympathetic renal nerve.

PMID- 9249251
TI  - Inhibition of eotaxin-mediated human eosinophil activation and migration by the
      selective cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram.
AB  - 1. The effect of the selective type 4 phosphodiesterase (PDE 4) inhibitor
      rolipram on human eosinophil activation and migration mediated by eotaxin was
      investigated. 2. Studies were performed with human freshly isolated eosinophils
      from peripheral blood of healthy donors by a magnetic cell separation (MACS)
      technique to a purity > 99%. To test the effect of rolipram, eosinophils were
      stimulated with recombinant human eotaxin and the cell surface activation markers
      CD11b and L-selectin were analysed by flow cytometry. Furthermore, eotaxin
      mediated eosinophil migration was measured in a transendothelial chemotaxis
      assay. 3. Our results indicate that rolipram inhibited eotaxin-induced CD11b up
      regulation up to 60.6 +/- 7.6% at the highest tested dose (10 microM), whereas
      transendothelial chemotaxis was partially inhibited reaching a plateau of approx.
      30% at a rolipram concentration of 0.1 microM. 4. We conclude that the selective
      PDE 4 inhibitor rolipram decreases eotaxin mediated eosinophil activation, an
      observation that may contribute to elucidate the mechanism by which PDE 4
      inhibitors reduce antigen-induced eosinophil infiltration in different animal
      models of allergic inflammation.

PMID- 9249252
TI  - Possible mechanisms underlying the midazolam-induced relaxation of the
      noradrenaline-contraction in rabbit mesenteric resistance artery.
AB  - 1. The mechanisms underlying the midazolam-induced relaxation of the
      noradrenaline (NA)-contraction were studied by measuring membrane potential,
      isometric force and intracellular concentration of Ca2+ ([Ca2+]i) in endothelium
      denuded muscle strips from the rabbit mesenteric resistance artery. The actions
      of midazolam were compared with those of nicardipine, an L-type Ca2+-channel
      blocker. 2. Midazolam (30 and 100 microM) did not modify either the resting
      membrane potential or the membrane depolarization induced by 10 microM NA. 3. NA
      (10 microM) produced a phasic, followed by a tonic increase in both [Ca2+]i and
      force. Midazolam (10-100 microM) did not modify the resting [Ca2+]i, but
      attenuated the NA-induced phasic and tonic increases in [Ca2+]i and force, in a
      concentration-dependent manner. In contrast, nicardipine (0.3 microM) attenuated
      the NA-induced tonic, but not phasic, increases in [Ca2+]i and force. 4. In Ca2+
      free solution containing 2 mM EGTA, NA (10 microM) transiently increased [Ca2+]i
      and force. Midazolam (10-100 microM), but not nicardipine (0.3 microM),
      attenuated this NA-induced increase in [Ca2+]i and force, in a concentration
      dependent manner. However, midazolam (10 and 30 microM), had no effect on the
      increases in [Ca2+]i and force induced by 10 mM caffeine. 5. In ryanodine-treated
      strips, which have functionally lost the NA-sensitive Ca2+ storage sites, NA
      slowly increased [Ca2+]i and force. Nicardipine (0.3 microM) did not modify the
      resting [Ca2+]i but partly attenuated the NA-induced increases in [Ca2+]i and
      force. In the presence of nicardipine, midazolam (100 microM) lowered the resting
      [Ca2+]i and further attenuated the remaining NA-induced increases in [Ca2+]i and
      force. 6. The [Ca2+]i-force relationship was obtained in ryanodine-treated strips
      by the application of ascending concentrations of Ca2+ (0.16-2.6 mM) in Ca2+-free
      solution containing 100 mM K+. NA (10 microM) shifted the [Ca2+]i-force
      relationship to the left and enhanced the maximum Ca2+-induced force. Under these
      conditions, whether in the presence or absence of 10 microM NA, midazolam (10 and
      30 microM) attenuated the increases in [Ca2+]i and force induced by Ca2+ without
      changing the [Ca2+]i-force relationship. 7. It was concluded that, in smooth
      muscle of the rabbit mesenteric resistance artery, midazolam inhibits the NA
      induced contraction through its inhibitory action on NA-induced Ca2+
      mobilization. Midazolam attenuates NA-induced Ca2+ influx via its inhibition of
      both nicardipine-sensitive and -insensitive pathways. Furthermore, midazolam
      attenuates the NA-induced release of Ca2+ from the storage sites. This effect
      contributes to the midazolam-induced inhibition of the NA-induced phasic
      contraction.

PMID- 9249253
TI  - Down-regulation of the hepatic cytochrome P450 by an acute inflammatory reaction:
      implication of mediators in human and animal serum and in the liver.
AB  - 1. Infection and inflammation trigger a cascade of mediators that eventually will
      down-regulate the hepatic cytochrome P450 (P450). The present study aimed to
      characterize the mediators contained in the serum of rabbits with an acute
      inflammatory reaction (AIR) induced by the s.c. injection of turpentine (5 ml),
      and in the serum of humans with an acute upper respiratory tract viral infection.
      2. Hepatocytes from control (H(CONT)) rabbits and rabbits with an AIR (H(INFLA))
      were isolated and cultured. Compared with H(CONT) in H(INFLA) the production of
      theophylline metabolites, 3-methylxanthine (3MX), 1-methyluric acid (1MU), and
      1,3-dimethyluric acid (1,3DMU) was reduced as was the amount of total P450, while
      lipid peroxidation was increased. Incubation of H(INFLA) with serum of rabbits
      with an AIR (RS(INFLA)) for 4 h further reduced the formation of the metabolites
      of theophylline as well as the amount of P450, and enhanced the lipid
      peroxidation. RS(INFLA) obtained 6, 12 and 24 h after the injection of turpentine
      showed the same ability to down-regulate hepatic P450 as the serum obtained at 48
      h. 3. The efficacy (Emax) of RS(INFLA) to inhibit the formation of theophylline
      metabolites differed, i.e. 1,3DMU > 1MU > 3MX, and the potency of serum mediators
      (IC50) was similar for 3MX and 1MU, but lower for 1,3DMU. 4. Incubation of serum
      of human volunteers (HS(INFLA)) with a viral infection with H(CONT) or H(INFLA)
      reduced the production of theophylline metabolites, as well as the amount of
      P450, and increased the lipid peroxidation. HS(INFLA) depressed 1,3DMU more
      efficiently than 3MX and 1MU. HS(INFLA) reduced 3MX with greater efficacy than
      did RS(INFLA). Potency was very variable but not different from rabbits. 5. It is
      concluded that the serum of rabbits with an AIR or of humans with a viral
      infection contain several mediators that inhibit noncompetitively various
      isoenzymes of the hepatic P450. The decrease in P450 induced by HS(INFLA) or
      RS(INFLA) is closely associated with the increase in lipid peroxidation (r2=
      0.8870) suggesting that lipid peroxidation could directly or indirectly be
      involved in the P450 down-regulation.

PMID- 9249254
TI  - NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely
      moving rats by microdialysis.
AB  - 1. Pilocarpine administration has been used as an animal model for temporal lobe
      epilepsy since it produces several morphological and synaptic features in common
      with human complex partial seizures. Little is known about changes in
      extracellular neurotransmitter concentrations during the seizures provoked by
      pilocarpine, a non-selective muscarinic agonist. 2. Focally evoked pilocarpine
      induced seizures in freely moving rats were provoked by intrahippocampal
      pilocarpine (10 mM for 40 min at a flow rate of 2 microl min(-1)) administration
      via a microdialysis probe. Concomitant changes in extracellular hippocampal
      glutamate, gamma-aminobutyric acid (GABA) and dopamine levels were monitored and
      simultaneous electrocorticography was performed. The animal model was
      characterized by intrahippocampal perfusion with the muscarinic receptor
      antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 microM)
      and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine
      maleate, 100 microM). The effectiveness of locally (600 microM) or systemically
      (10 mg kg(-1) day(-1)) applied lamotrigine against the pilocarpine-induced
      convulsions was evaluated. 3. Pilocarpine initially decreased extracellular
      hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced
      limbic convulsions extracellular glutamate, GABA and dopamine concentrations in
      hippocampus were significantly increased. Atropine blocked all changes in
      extracellular transmitter levels during and after co-administration of
      pilocarpine. All pilocarpine-induced increases were completely prevented by
      simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801
      and lamotrigine resulted in an elevation of hippocampal dopamine levels and
      protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced
      convulsions developed in the rats which received lamotrigine perorally. 4.
      Pilocarpine-induced seizures are initiated via muscarinic receptors and further
      mediated via NMDA receptors. Sustained increases in extracellular glutamate
      levels after pilocarpine perfusion are related to the limbic seizures. These are
      arguments in favour of earlier described NMDA receptor-mediated excitotoxicity.
      Hippocampal dopamine release may be functionally important in epileptogenesis and
      may participate in the anticonvulsant effects of MK-801 and lamotrigine. The
      pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect
      neuronal vesicular release.

PMID- 9249255
TI  - Differential effects of the neuropeptide galanin on striatal acetylcholine
      release in anaesthetized and awake rats.
AB  - 1. In the present study the mechanisms were examined by which the neuropeptide
      galanin modulates the extracellular concentrations of striatal acetylcholine
      (ACh) in enflurane anaesthetized and in freely moving male rats by use of in vivo
      microdialysis and high performance liquid chromatography. 2. The perfusion of
      galanin through the microdialysis probe (0.3 nmol microl(-1), flow rate: 2 microl
      min(-1)) caused a statistically significant increase in the basal striatal ACh
      levels in anaesthetized but a decrease in awake animals. No significant effect
      was revealed after a low dose (0.1 nmol microl(-1), flow rate: 2 microl min(-1))
      of galanin perfusion. Both the stimulating and inhibitory effects of galanin on
      basal ACh release were reversible. 3. The muscarinic antagonist scopolamine (0.1
      mg kg(-1), subcutaneously (s.c.)) caused a significant increase in ACh release in
      both anaesthetized and awake animals. 4. The combination of galanin plus
      scopolamine attenuated the stimulant effect on ACh release caused by scopolamine
      alone in awake animals. 5. The putative galanin receptor antagonist M35 at 0.3
      nmol microl(-1) but not at 0.1 nmol microl(-1) caused a significant reduction
      (20%) in ACh release, supporting the view that M35 at higher concentrations
      behaves as a partial agonist at the galanin receptor. When M35 (0.1 nmol microl(
      1)) was co-infused with galanin (0.3 nmol microl(-1)) the galanin-evoked decrease
      in ACh release was completely blocked. 6. Taken together, these results indicate
      that galanin affects basal ACh release via stimulation of galanin receptors
      within the striatum. The mechanism involved is dependent on the anaesthesia
      procedure which may act via enhancement of gamma-aminobutyric acidA (GABA(A))
      mediated transmission within striatal and/or output neurones. In addition,
      anaesthesia may also decrease the activity of glutamatergic striatal afferents.
      The results with M35 indicate that the role of galanin perfused in striatum is
      permissive in the normal rat. Furthermore, galanin is a potent inhibitory
      modulator of basal ACh release also in the striatum, as recently was shown in the
      ventral hippocampus in awake animals.

PMID- 9249256
TI  - Characterization of putative 5-HT7 receptors mediating tachycardia in the cat.
AB  - 1. It has been suggested that the tachycardic response to 5-hydroxytryptamine (5
      HT) in the spinal-transected cat is mediated by '5-HT1-like' receptors since this
      effect, being mimicked by 5-carboxamidotryptamine (5-CT), is not modified by
      ketanserin or MDL 72222, but it is blocked by methiothepin, methysergide or
      mesulergine. The present study was set out to reanalyse this suggestion in terms
      of the IUPHAR 5-HT receptor classification schemes proposed in 1994 and 1996. 2.
      Intravenous (i.v.) bolus injections of the tryptamine derivatives, 5-CT (0.01,
      0.03, 0.1, 0.3, 1, 3, 10 and 30 microg kg(-1)), 5-HT (3, 10 and 30 microg kg(-1))
      and 5-methoxytryptamine (3, 10 and 30 microg kg(-1)) as well as the atypical
      antipsychotic drug, clozapine (1000 and 3000 microg kg(-1)) resulted in dose
      dependent increases in heart rate, with a rank order of agonist potency of 5-CT
      >> 5-HT > 5-methoxytryptamine >> clozapine. 3. The tachycardic effects of 5-HT
      and 5-methoxytryptamine were dose-dependently antagonized by i.v. administration
      of lisuride (30 and 100 microg kg(-1)), ergotamine (100 and 300 microg kg(-1)) or
      mesulergine (100, 300 and 1000 microg kg(-1)); the highest doses of these
      antagonists used also blocked the tachycardic effects of 5-CT. Clozapine (1000
      and 3000 microg kg(-1)) did not affect the 5-HT-induced tachycardia, but
      attenuated, with its highest dose, the responses to 5-methoxytryptamine and 5-CT.
      However, these doses of clozapine as well as the high doses of ergotamine (300
      microg kg(-1)) and mesulergine (300 and 1000 microg kg(-1)) also attenuated the
      tachycardic effects of isoprenaline. In contrast, 5-HT-, 5-methoxytryptamine- and
      5-CT-induced tachycardia were not significantly modified after i.v.
      administration of physiological saline (0.1 and 0.3 ml kg(-1)), the 5-HT(1B/1D)
      receptor antagonist, GR127935 (500 microg kg(-1)) or the 5-HT(3/4) receptor
      antagonist, tropisetron (3000 microg kg(-1)). 4. Intravenous injections of the 5
      HT1 receptor agonists, sumatriptan (30, 100 and 300 microg kg(-1)) and indorenate
      (300 and 1000 microg kg(-1)) or the 5-HT4 receptor (partial) agonist cisapride
      (300 and 1000 microg kg(-1)) were devoid of effects on feline heart rate per se
      and failed to modify significantly 5-HT-induced tachycardic responses. 5. Based
      upon the above rank order of agonist potency, the failure of sumatriptan,
      indorenate or cisapride to produce cardioacceleration and the blockade by a
      series of drugs showing high affinity for the cloned 5-ht7 receptor, the present
      results indicate that the 5-HT receptor mediating tachycardia in the cat is
      operationally similar to other putative 5-HT7 receptors mediating vascular and
      non-vascular responses (e.g. relaxation of the rabbit femoral vein, canine
      external carotid and coronary arteries, rat systemic vasculature and guinea-pig
      ileum). Since these responses represent functional correlates of the 5-ht7 gene
      product, the 5-HT7 receptor appellation is reinforced. Therefore, the present
      experimental model, which is not complicated by the presence of other 5-HT
      receptors, can be utilized to characterize and develop new drugs with potential
      agonist and antagonist properties at functional 5-HT7 receptors.

PMID- 9249257
TI  - Noradrenaline release and the effect of endogenous activation of the
      phospholipase C/protein kinase C signalling pathway in rat atria.
AB  - 1. It has been proposed that protein kinase C (PKC) in sympathetic nerves is
      activated during action-potential evoked release of noradrenaline and helps
      maintain transmitter output. We studied this phenomenon further in rat atria
      radiolabelled with [3H]-noradrenaline. 2. Noradrenaline release was elevated by
      continuous electrical stimulation of the atria for 10 min at either 5 or 10 Hz.
      Two inhibitors of PKC, polymyxin B (21 microM) and Ro 318220 (3 microM), markedly
      inhibited the release of noradrenaline but only at the higher stimulation
      frequency. 3. Further experiments were conducted with 10 Hz stimulation but for
      shorter train durations. In this case polymyxin B inhibited noradrenaline release
      during a 10 or 15 s train of impulses but not during a 5 s train. This suggests
      that PKC effects are induced during the stimulation train by some process. 4. The
      diacylglycerol kinase inhibitor R59949 (10 microM), which prevents the breakdown
      of diacylglycerol, enhanced noradrenaline release elicited by stimulation at 10
      Hz for 10 or 15 s. This effect was not seen if polymyxin B was present and
      suggests that diacylglycerol is the endogenous activator of PKC. 5. The source of
      the diacylglycerol may be through phospholipase C pathways, since the
      phospholipase C inhibitor U73122 (3 microM) inhibited noradrenaline release at 10
      Hz for 10 s and the effect was not seen if polymyxin B was also present. 6. It is
      unlikely that phospholipase D is the source of diacylglycerol. Although the
      phospholipase D inhibitor wortmannin (1 microM) inhibited noradrenaline release,
      this effect was still observed in the presence of polymyxin B. Furthermore
      ethanol, which inhibits diacylglycerol formation by phospholipase D, had no
      effect on noradrenaline release. 7. We therefore suggest that during a train of
      high frequency pulses phospholipase C is activated and this results in the
      production of diacylglycerol which in turn activates PKC. This enables the
      neurones to maintain transmitter release at a high level.

PMID- 9249258
TI  - Pharmacological characterization of type 1alpha metabotropic glutamate receptor
      stimulated [35S]-GTPgammaS binding.
AB  - 1. The activation of G proteins by type 1alpha metabotropic glutamate receptors
      (mGluRs) in membranes from recombinant baby hamster kidney cells expressing the
      cloned rat mGluR1alpha receptor has been studied by use of a [35S]-guanosine 5'
      [gamma-thio]triphosphate ([35S]-GTPgammaS) binding assay. 2. L-Glutamate
      increased the rate of [35S]-GTPgammaS binding in a concentration-dependent manner
      (-logEC50 (M) 5.25 +/- 0.07), with an optimal (62.4 +/- 1.6%) increase over basal
      binding being observed following 60 min incubation at 30 degrees C with 70 pM
      [35S]-GTPgammaS, 1 microM GDP, 10 mM MgCl2, 100 mM NaCl and 100 microg membrane
      protein ml(-1). The L-glutamate (100 microM)-stimulated increase in [35S]
      GTPgammaS binding was totally prevented in the presence of the group I mGluR
      antagonist (S)-4-carboxy-3-hydroxyphenylglycine (300 microM). 3. Quantitative
      analysis of the affinity and number of G proteins activated by a maximally
      effective concentration of L-glutamate revealed an equilibrium dissociation
      constant (K(D)) for [35S]-GTPgammaS binding of 0.76 +/- 0.20 nM and a maximal
      number of GTPgammaS-liganded G proteins (Bmax) of 361 +/- 30 fmol mg(-1) protein.
      4. Metabotropic glutamate receptor agonists, quisqualate (-logEC50 (M) 6.74 +/-
      0.06), 1S,3R-ACPD (4.64 +/- 0.08) and (S)-3,5-dihydroxyphenylglycine (5.16 +/-
      0.23) also increased [35S]-GTPgammaS binding in a concentration-dependent manner,
      with the latter two agents behaving as partial agonists. 5. (+)-alpha
      Methylcarboxyphenylglycine (300 microM) caused a parallel rightward shift of the
      L-glutamate concentration-effect curve for [35S]-GTPgammaS binding, allowing an
      antagonist equilibrium dissociation constant (K(D)) of 34.0 +/- 7.8 microM to be
      calculated for this mGluR antagonist. 6. Pretreatment of BHK-mGluR1alpha cells
      with a concentration of pertussis toxin (PTX) shown to be maximally effective
      (100 ng ml(-1), 24 h) before membrane preparation resulted in a marked decrease
      in agonist-stimulated [35S]-GTPgammaS binding (by 66.0 +/- 0.9%), and an altered
      concentration-effect relationship for agonist-stimulated [35S]-GTPgammaS binding
      by the residual PTX-insensitive G-protein population. 7. The modulation of [35S]
      GTPgammaS binding by agonists and antagonists in membranes from recombinant cells
      provides an excellent system in which to study mGluR interactions with PTX
      sensitive and -insensitive G proteins.

PMID- 9249259
TI  - Differential antinociceptive effects of spinal opioids on foot withdrawal
      responses evoked by C fibre or A delta nociceptor activation.
AB  - 1. Intrathecal application of mu, delta, and kappa opioids attenuate responses on
      several tests of animal nociception. However, the potency of these opioids differ
      depending on which tests were used. One factor contributing to these
      discrepancies is that different types of noxious stimuli activate different sets
      of nociceptor types, which may be differentially sensitive to opiate inhibition.
      To examine this hypothesis, we used a recently developed behavioural test which
      allows for differential assessment of nociception evoked by the activation of
      myelinated (A delta) and unmyelinated C thermonociceptors. 2. Administration of a
      kappa-selective agonist was ineffective on either type of response. Delta1 drugs
      were slightly more potent on C fibre-mediated responses than on A delta-mediated
      responses. 3. Intrathecal mu and delta2 drugs were antinociceptive on both A
      delta and C nociceptor-mediated responses. However, unlike the delta1 effects,
      the dose-response curves for mu and delta2 drugs were significantly more steep
      for A delta than for C fibre-mediated responses, potentially indicating
      differences in the mechanisms by which the drugs act on these 2 response types.

PMID- 9249260
TI  - Inhibition of muscarinic K+ current in guinea-pig atrial myocytes by PD 81,723,
      an allosteric enhancer of adenosine binding to A1 receptors.
AB  - 1. PD 81,723 has been shown to enhance binding of adenosine to A1 receptors by
      stabilizing G protein-receptor coupling ('allosteric enhancement'). Evidence has
      been provided that in the perfused hearts and isolated atria PD 81,723 causes a
      sensitization to adenosine via this mechanism. 2. We have studied the effect of
      PD 81,723 in guinea-pig isolated atrial myocytes by use of whole-cell measurement
      of the muscarinic K+ current (I[K(ACh)]) activated by different Gi-coupled
      receptors (A1, M2, sphingolipid). PD 81,273 caused inhibition of I[K(ACh)] (IC50
      approximately 5 microM) activated by either of the three receptors. Receptor
      independent I[K(ACh)] in cells loaded with GTP-gamma-S and background I[K(ACh)],
      which contributes to the resting conductance of atrial myocytes, were equally
      sensitive to PD 81,723. At no combination of concentrations of adenosine and PD
      81,723 could an enhancing effect be detected. 3. The compound was active from the
      outside only. Loading of the cells with PD 81,723 (50 microM) via the patch
      pipette did not affect either I[K(ACh)] or its sensitivity to adenosine. We
      suggest that PD 81,723 acts as an inhibitor of inward rectifying K+ channels;
      this is supported by the finding that ventricular I(K1), which shares a large
      degree of homology with the proteins (GIRK1/GIRK4) forming I[K(ACh)] but is not G
      protein-gated, was also blocked by this compound. 4. It is concluded that the
      functional effects of PD 81,723 described in the literature are not mediated by
      the A1 adenosine receptor-Gi-I[K(ACh)] pathway.

PMID- 9249261
TI  - Selective depolarization of the muscle membrane in frog nerve-muscle preparations
      by a chromatographically purified extract of the dinoflagellate Ostreopsis
      lenticularis.
AB  - 1. The actions of a chromatographically identified extract of the marine
      dinoflagellate Ostreopsis lenticularis, named ostreotoxin-3 (OTX-3), were studied
      on frog isolated neuromuscular preparations. 2. OTX-3 (1-10 microg ml(-1))
      applied to cutaneous pectoris nerve-muscle preparations depolarized skeletal
      muscle fibres and caused spontaneous contractions. The depolarization was neither
      reversed by prolonged washing nor by (+)-tubocurarine. 3. OTX-3 decreased the
      amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their
      frequency. 4. Extracellular recording of compound action potentials revealed that
      OTX-3 affected neither excitability nor conduction along intramuscular nerve
      branches. 5. End-plate potentials (e.p.ps) elicited by nerve stimulation were
      reduced in amplitude by OTX-3 and even showed reversed polarity in junctions
      deeply depolarized by the toxin. 6. Membrane depolarization induced by OTX-3 was
      decreased about 70% in muscles pretreated for 30 min with 10 microM tetrodotoxin.
      In contrast, muscles pretreated with 5 microM mu-conotoxin GIIIA were completely
      insensitive to OTX-3-induced depolarization. 7. OTX-3 did not affect e.p.p.
      amplitude and the quantal content of e.p.ps in junctions in which muscle
      depolarization was abolished by mu-conotoxin GIIIA. 8. OTX-3 is a novel type of
      sodium-channel activating toxin that discriminates between nerve and skeletal
      muscle membranes.

PMID- 9249262
TI  - Characterization of lamotrigine inhibition of Na+ channels in rat hippocampal
      neurones.
AB  - 1. Lamotrigine (LTG), a new antiepileptic drug, requires long depolarizations to
      inhibit Na+ currents. This suggests either slow binding of LTG to the fast
      inactivated state or selective binding of LTG to the slow inactivated state of
      Na+ channels. To differentiate between these possibilities and to characterize
      further the action of LTG, we studied the affinity and kinetics of LTG binding to
      the Na+ channels in acutely dissociated hippocampal neurones of the rat. 2. LTG
      inhibited more Na+ currents at more depolarized holding potentials. The
      inhibitory effect at various holding potentials could be described by one-to-one
      binding curves, which yielded an apparent dissociation constant of approximately
      7 microM for LTG binding to the inactivated channels (K(I)), and a dissociation
      constant more than 200 times larger for LTG binding to the resting channels. A
      similar value of K(I) (approximately 9 microM) was also derived from the LTG
      concentration-dependent shift of the inactivation curve. 3. The recovery of LTG
      bound inactivated Na+ channels was faster than the recovery of normal (drug-free)
      slow inactivated channels. Moreover, the binding kinetics of LTG onto the
      inactivated channels were faster than the development of the slow inactivated
      state, and were linearly correlated with LTG concentrations, with a binding rate
      constant of approximately 10,000 M(-1) s(-1). These findings suggest that LTG
      chiefly binds to the fast inactivated state rather than the slow inactivated
      state. 4. We conclude that LTG, in therapeutic concentrations and at relatively
      depolarized membrane potentials, may potently inhibit Na+ currents by slow
      binding to the fast inactivated state of Na+ channels. Like phenytoin, the slow
      binding rates may explain why LTG effectively inhibits seizure discharges, yet
      spares most normal neuronal activities.

PMID- 9249263
TI  - Epithelial ICAM-1 regulation and its role in allergy.

PMID- 9249264
TI  - Thunderstorm-related asthma--the epidemic of 24/25 June 1994.
AB  - BACKGROUND: A large epidemic of asthma occurred following a thunderstorm in
      southern and central England on 24/25 June 1994. A collaborative study group was
      formed. OBJECTIVES: To describe the epidemic and the meteorological,
      aerobiological and other environmental characteristics associated with it.
      METHODS: Collation of data from the Meteorological Office, the Pollen Research
      Unit, the Department of the Environment's Automatic Urban Network, from health
      surveillance by the Department of Health and the National Poisons Unit, from
      clinical experience in general practice and hospitals, and from an immunological
      study of some of the affected cases from north east London. RESULTS: The
      thunderstorm was a Mesoscale Convective System, an unusual and large form of
      storm with several centres and severe wind gusts. It occurred shortly after the
      peak grass pollen concentration in the London area. A sudden and extensive
      epidemic occurred within about an hour affecting possibly several thousand
      patients. Emergency services were stretched but the epidemic did not last long.
      Cases had high serum levels of IgE antibody to mixed grass pollen. CONCLUSION:
      This study supports the view that patients with specific IgE to grass pollen are
      at risk of thunderstorm-related asthma. The details of the causal pathway from
      storm to asthma attack are not clear. Case-control and time series studies are
      being carried out.

PMID- 9249265
TI  - In situ hybridization analysis of ICAM-1 (CD54) mRNA on conjunctival epithelium
      during allergic inflammation.
AB  - BACKGROUND: The intercellular adhesion molecule ICAM-1 has been detected by
      immunohistochemical methods on epithelial cells of the conjunctiva and nose
      during allergic inflammation. OBJECTIVE: The aim of the present study was to
      evaluate whether ICAM-1 expression on conjunctival epithelium derives from
      endogenous synthesis or is merely due to passive uptake of soluble ICAM-1
      released from inflammatory cells. METHODS: In situ hybridization was performed
      using a 3' end dygoxygenin-labelled specific DNA oligonucleotide probe on fixed
      conjunctival smears from allergic subjects challenged with, or naturally exposed
      to the allergen, and from healthy subjects. Immunocytochemistry for ICAM-1 was
      performed by alkaline phosphatase antialkaline phosphatase. RESULTS: In allergic
      patients, both naturally exposed to the allergen and after specific challenge, a
      clear hybridization pattern on epithelial cells was apparent. Out of allergen
      exposure, some symptomfree pollinosic subjects, as well as a few healthy
      volunteers showed mild ICAM-1 mRNA cytoplasmic staining in the absence of
      immunohistochemically detectable ICAM-1. This finding may explain the very early
      appearance of ICAM-1 on conjunctival epithelium following specific challenge in
      allergic individuals. CONCLUSIONS: These results indicate that the presence of
      ICAM-1 on conjunctival epithelium during allergic inflammation derives from
      endogenous synthesis and not from uptake of soluble ICAM-1.

PMID- 9249266
TI  - Reduction of exposure to laboratory animal allergens in the workplace.
AB  - OBJECTIVES: Evidence is now accumulating that the prevalence of allergy to
      laboratory animals is related to the intensity of exposure to animal allergens.
      Whilst airborne animal allergen concentrations may be influenced by the litter
      type, cage design and stock density, the effectiveness of methods to reduce
      personal exposure has not been objectively assessed. METHODS: Air samples were
      collected at 2 L/min and 180 L/min onto polytetrafluoroethylene (PTFE) filters
      and the rat urinary aeroallergen (RUA) and mouse urinary aeroallergen (MUA)
      concentrations were measured by radioallergosorbent test (RAST) inhibition.
      RESULTS: When 545 mice (11.l mice/m3) were housed in ventilated cages (Thoren
      Maximiser cage system) operated at positive pressure to the environment, the
      static MUA concentration (n = 24, median = 0.10 microg/m3) was reduced sevenfold
      when compared with conventional cage systems (n = 12, median =0.67 microg/m3, P<
      0.001). MUA could be further reduced if the ventilated cage system was operated
      at lower pressure; static samples (n = 1) collected at 180 L/min at negative,
      ambient and positive pressure registered < 0.003, 0.02 and 0.28 microg/m3,
      respectively. During cleaning out, the intensity of personal exposure to RUA was
      apparently reduced twofold when soiled litter was removed by vacuum (n = 17,
      median = 22.87 microg/m3) when compared with tipping (n = 18, median = 38.15
      microg/m3), P = 0.002) although the task took twice as long to perform. The RUA
      exposure associated with handling rats was'reduced 25-fold when performed in a
      ventilated cabinet (n = 21, median = 2.67 microg/m3) compared with handling of
      rats on an open bench (n = 17, median = 54.39 microg/m3, P = 0.0001).
      CONCLUSIONS: Effective reduction of exposure to animal allergens can now be
      achieved by the use of ventilated systems both for housing and handling rats and
      mice providing safety equipment is used correctly. The vacuum removal of soiled
      litter during the task of cleaning out was less efficient and additional
      respiratory protection is therefore recommended for this procedure.

PMID- 9249267
TI  - Predictability of early atopy by cord blood-IgE and parental history.
AB  - BACKGROUND: Atopic family history and cord blood IgE have been used as predictors
      of atopic disease in newborns for about 20 years, but at least for cord blood IgE
      the sensitivity has been shown to be very low. The objective of this paper was to
      evaluate whether parental history and cord blood-IgE were more accurate
      predictors for the appropriate atopic phenotypes in the infants rather than for
      any atopy. METHODS: A total of 1314 newborn infants was recruited in six German
      obstetric departments in 1990 and followed-up for 2 years. Four hundred and
      ninety-nine (38%) were at high risk for atopy with at least two first degree
      atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The
      cumulative incidence of atopic dermatitis over the first 2 years of life (AD24)
      amounted to 20.1%, and there was a significant association with AD history of the
      mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54).
      The cumulative incidence of recurrent wheezing in the first 2 years of life
      (RW24) amounted to 16.1%, and was positively associated with asthma history (OR
      2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of
      the mother, but with neither for the father. RW24 was less prevalent in girls
      than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were
      sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or
      inhalative allergens (S24) and this was significantly associated with cord blood
      IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR
      1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the
      prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of
      sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive
      capacity of parental history and cord blood IgE is not high enough to recommend
      them as screening instruments for primary prevention. The majority of atopic
      manifestations and of sensitization occur in infants with no demonstrable risk at
      birth.

PMID- 9249268
TI  - Prevalence of childhood asthma based on questionnaires and methacholine bronchial
      provocation test in Korea.
AB  - BACKGROUND: In most epidemiological survey studies, only subjective symptoms and
      past medical history of asthma have been used as diagnostic criteria. Even though
      a questionnaire survey can be performed in a large population study at low cost,
      limitations such as lack of objectivity and poor predictability in non-specific
      bronchial hyperresponsiveness cannot be avoided. OBJECTIVES: The purpose of this
      study was to elucidate the prevalence of current asthma based on questionnaires
      and methacholine bronchial provocation test, and the prevalence of atopy in
      Korea. METHODS: We performed modified ATS respiratory questionnaires and allergen
      skin-prick test with 10 common inhalant allergens among 3219 subjects aged 7-19
      years in Seoul and a rural part of a small city, Chungju in Korea. Methacholine
      bronchial provocation tests were also performed among those who had asthma
      symptoms according to the questionnaire. The criteria of asthma was presence of
      both asthma symptoms and non-specific bronchial hyperresponsiveness. Atopy was
      defined as when an allergen induced weal size is same or larger than that caused
      by histamine. RESULTS: The prevalence of asthma based on questionnaires and
      methacholine bronchial provocation tests was 4.6%, while the prevalence of wheeze
      was 8.2% and 19.3% of total population complained of one or more respiratory
      symptoms related to asthma on the questionnaires. There was no significant
      difference according to age, sex and living area. The mean prevalence of atopy
      was 35.0% and the most common allergens were Dermatophagoides farinae (30.9%),
      Dermatophagoides pteronyssinus (27.5%), cat fur (20.4%) and cockroach (11.8%).
      The atopy prevalence in Chungju area was higher than that in Seoul and males
      showed a higher prevalence than females. The asthma prevalence was higher among
      atopics (6.8%) than among non-atopics (2.7%). None of questionnaire items were
      enough to predict the presence of bronchial hyperresponsiveness in terms of
      sensitivity, specificity and positive predictive value. CONCLUSION: The
      prevalence rate of current asthma in Korea was 4.6% and the prevalence rate of
      atopy in Korea was 35.0%. Questionnaire-based surveys are not enough to predict
      the actual prevalence of asthma.

PMID- 9249269
TI  - Comparison of inflammatory cell counts in asthma: induced sputum vs
      bronchoalveolar lavage and bronchial biopsies.
AB  - BACKGROUND: Induced sputum potentially allows monitoring of airway inflammation
      in patients with asthma in a non-invasive way. However, the relationship between
      the cellular content in sputum and airway tissue has not been fully clarified.
      OBJECTIVE: We compared the cellular compositions of hypertonic saline-induced
      sputum, bronchoalveolar lavage fluid (BAL) and bronchial biopsies in 18
      clinically stable patients with mild to moderate atopic asthma (baseline FEV1:
      range 61-114%pred, PC20 methacholine: 0.04-4.7 mg/mL). They were treated with
      inhaled short-acting bronchodilators on demand, with (n = 8) or without (n = 10)
      regular inhaled steroids. METHODS: Each patient underwent sputum induction and
      fiberoptic bronchoscopy on separate days in random order. Differential cell
      counts of induced sputum, bronchoalveolar lavage and bronchial wash were
      determined on May-Grunwald-Giemsa stained cytospins. Flow cytometry was performed
      on sputum and BAL samples. Immunohistochemical techniques were used to stain
      inflammatory cells in 6 microm cryostat sections of bronchial biopsies. RESULTS:
      Sputum cell differentials were not different between the patients with and
      without inhaled steroids, and showed a median value of 19.4% squamous cells, with
      1.0% eosinophils, 3.3% lymphocytes, 28.7% neutrophils, 49.4% macrophages and 6.9%
      cylindric epithelial cells (in percentage non-squamous cells). The percentage
      eosinophils in sputum was significantly correlated with their percentage in
      bronchial wash (Rs = 0.52, P = 0.03) and in BAL (Rs = 0.55, P= 0.02), whilst
      there was a trend towards such a correlation between the number of eosinophils/mL
      sputum and the number of EG2+ eosinophils/mm2 lamina propria in bronchial
      biopsies (Rs = 0.44, P = 0.07). In addition, the percentage of CD4+ lymphocytes
      correlated between sputum and BAL (Rs = 0.55, P = 0.03). CONCLUSION: We conclude
      that the eosinophil counts in hypertonic saline-induced sputum from patients with
      asthma are related to those in bronchial wash and BAL and, to a lesser extent,
      with the counts in bronchial biopsies. This suggests that induced sputum can be
      used to monitor the presence and severity of airway inflammation in asthma.

PMID- 9249270
TI  - Allergen-induced CD30 expression on T cells of atopic asthmatics.
AB  - BACKGROUND: The importance of TH2-type T cell cytokines in atopic disease is
      widely accepted. CD30, a member of the TNF/NGF receptor superfamily, is expressed
      on a proportion of activated CD45RO+ T cells and has been proposed as a marker
      for TH2 phenotype. CD30 ligand-CD30 interaction has been shown to positively
      influence development of the TH2 phenotype, and serum levels of soluble CD30
      (sCD30) have been used as prognostic markers in HIV, SLE, Epstein-Barr Virus
      infection and Hodgkin's Lymphoma but not as yet in allergic disease. OBJECTIVES:
      To establish if serum levels of sCD30 are elevated in atopic asthma and determine
      whether allergen-induced proliferation/activation of PBMCs from atopic asthmatics
      promotes CD30 expression on CD4+ T lymphocytes. Further, to determine if
      expression of CD30 and sCD30 correlate with disease severity. METHODS: Eighteen
      atopic asthmatics were each assigned a symptomatic disease score based on
      symptoms and bronchodilator rescue usage. Serum sCD30 was measured in peripheral
      blood by ELISA. PBMCs from atopic asthmatics were analysed with flow cytometry to
      obtain the proportions of CD4+ T cells expressing CD45RO and CD30. The cells were
      then cultured for 10 days with IL-2 with or without house dust mite antigen. A
      proliferation index was recorded and expression of CD30 and CD45RO retested. As a
      control, stimulation with PHA was used. Results with patients' PBMCs were
      compared with results of a parallel analysis of PBMCs from non-atopic healthy
      controls. RESULTS: Serum sCD30 was elevated in the 18 atopic asthmatics compared
      with a group of normal subjects but levels did not correlate with symptomatic
      disease activity. CD4CD45RO expression was low (14%) in atopic asthmatic
      peripheral blood but increased to 41% after 10 days culture with allergen. The
      CD4:CD8 ratio increased after Der p stimulation. A significant rise in the
      percentage of CD4+ T cells expressing surface CD30 (29%) was seen along with
      increased mean fluorescence intensity. Both these results correlated with
      symptomatic disease severity score. Non-specific PHA stimulation failed to
      significantly affect CD30 expression. CONCLUSIONS: There is a specific response
      to allergen in atopic asthma which causes significant increases in CD30
      expression. This may correlate with disease severity.

PMID- 9249271
TI  - Some alterations of the leucocyte beta2-adrenoceptor/cAMP-system in patients with
      seasonal allergic rhinoconjunctivitis are related to disease activity.
AB  - BACKGROUND: Disturbances of beta2-adrenoceptors are discussed as a pathogenic
      factor in atopic diseases. METHODS: In this study the expression and function of
      beta2-adrenoceptors on peripheral blood leucocytes (PBL) of seven atopic patients
      with seasonal rhinoconjunctivitis and their seven healthy controls was evaluated
      in relation to disease activity. Earlier reported data during pollen season were
      now compared with data obtained from the same subjects after their allergic
      symptoms had subsided. RESULTS: The variables that had indicated a beta2
      adrenoceptor subsensitivity in the patients during pollen season returned to
      control values, i.e. the reduced beta2-adrenoceptor affinity, the reduced beta2
      adrenoceptor sensitivity, the reduced increase of intracellular cyclic adenosine
      monophosphate (cAMP) content upon stimulation with isoproterenol, and the reduced
      cAMP plasma concentration (values no longer significantly different from those of
      controls). However, the variable that had suggested an increase in activity of
      the cAMP degrading enzyme phosphodiesterase (PDE), i.e. the reduced basal
      intracellular cAMP content of the patients, remained reduced after the pollen
      season (4.9 +/- 1.1 pmol/10(6) cells in patients vs 8.2 +/- 0.9 pmol/10(6) cells
      in controls: P<0.05). There were no significant differences in beta2-adrenoceptor
      density between patients and controls at both investigations. CONCLUSIONS: Atopic
      seasonal rhinoconjunctivitis is associated with various alterations in the PBL
      beta2-adrenoceptor/cAMP system that depend on disease activity. The reversible
      beta2-adrenoceptor subsensitivity is likely to be a consequence of the disease,
      whereas the irreversibly decreased basal intracellular cAMP content, suggested an
      elevated PDE activity, might be a basic trait of atopy.

PMID- 9249272
TI  - Intranasal capsaicin is efficacious in non-allergic, non-infectious perennial
      rhinitis. A placebo-controlled study.
AB  - BACKGROUND: Several authors described capsaicin, the pungent substance in red
      pepper, as an efficacious therapy for non-allergic non-infectious perennial
      rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and
      specific degeneration of the unmyelinated sensory C-fibres in the nasal mucosa.
      METHODS: We performed a placebo-controlled (NaCl 0.9%) study with 25 NANIPER
      patients. Daily record charts and visual analogue scales (VAS) were used for
      clinical evaluation. Nasal lavages were obtained before, during, and after
      treatment. RESULTS: There was a significant and long-term reduction in the VAS
      scores in the capsaicin group. No significant difference was found between the
      placebo and capsaicin treated groups for the mean group concentrations of
      leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2), and tryptase. The levels of
      mast cell mediators, tryptase and PGD2, and leukotrienes, mediators derived from
      a variety of inflammatory cells, were low at baseline and comparable with levels
      observed in nasal lavages obtained from normals. CONCLUSION: As involvement of
      inflammation could not be demonstrated, it is not surprising that capsaicin has
      no effect on inflammatory mediators. This suggests that inflammatory cells do not
      play a major part in the pathogenesis of NANIPER.

PMID- 9249273
TI  - Dysfunction of guinea-pig pulmonary surfactant and type II pneumocytes after
      repetitive challenge with aerosolized ovalbumin.
AB  - BACKGROUND: Asthma symptoms may partially be caused by a surfactant dysfunction.
      The inflammatory reaction, so characteristic of asthma, involves a protein
      invasion of airways which harmfully affects the surfactant function. However,
      mild asthma attacks might also impede the surfactant synthesis in alveolar type
      II cells. OBJECTIVE: The present study evaluates the hypothesis that type II
      pneumocyte metabolic function might be disturbed in a model of mild asthma.
      METHODS: Immunized, as well as not immunized control guinea-pigs, were challenged
      three times at two-day intervals with 0.04% ovalbumin aerosol. Bronchoalveolar
      lavage (BAL) was performed one day after the last challenge and the fluid was
      evaluated for surface activity, and content of phospholipids and proteins.
      Alveolar type II cells were isolated and their ability to incorporate a 3H
      labeled surfactant precursor was evaluated. RESULTS: BAL fluid from immunized and
      challenged animals showed less surface activity (P < 0.01) when compared with BAL
      fluid from controls, not immunized but challenged. Most likely the reduced
      surface activity was caused by a 74% increase in the protein concentration (P <
      0.05). Isolated type II cells from immunized and challenged animals had 33% less
      phospholipids than cells from controls (P < 0.05), and phosphatidylcholine
      synthesis was reduced 35% (P < 0.05). CONCLUSION: These results suggest that the
      synthesis, intra-cellular storage, and biophysical activity of surfactant are
      decreased in an intermittent and mild form of asthma.

PMID- 9249274
TI  - Specific induction of interleukin-4-producing cells in response to in vitro
      allergen stimulation in atopic individuals.
AB  - BACKGROUND AND OBJECTIVE: CD4+ T cells can be divided into two major subsets, T
      helper (TH)1 and TH2 cells. Interleukin-4 (IL-4) is produced by TH2 cells and
      induces switching of immunoglobulin (Ig) M/IgG to IgE. Interferon-gamma
      (IFNgamma) produced by TH1 cells counteracts the IgE-promoting effects of IL-4.
      In this study we wanted to investigate whether the number of IL-4-producing cells
      could be a direct measurement of allergen exposure in vitro, and whether this was
      correlated to the elevated serum IgE-levels seen in atopic persons. METHODS: We
      compared the number of IL-4- and IFNgamma-producing cells using an enzyme-linked
      immunospot assay (ELISPOT) in response to allergens from birch and cat in
      peripheral mononuclear cells from atopic and healthy individuals. RESULTS: In the
      two sensitized groups there was an increase in the number of IL-4-producing cells
      in response to the specific allergen which was not seen in the healthy group
      (1/20000 cells and 1/200000 cells, respectively, P < 0.001 for birch). In criss
      cross experiments where birch-sensitized individuals were stimulated with cat
      allergen, no IL-4-producing cells were seen, indicating a high degree of
      specificity. In individual subjects, the elevated numbers of IL-4-producing cells
      were significantly correlated with their allergen-specific serum IgE levels. When
      allergen was combined with a suboptimal dose of PHA, there was a synergistic
      increase in the number of allergen-induced IL-4-producing cells (1/4000 cells) in
      the atopic donors, which was not seen with the number of IFNgamma-producing
      cells. CONCLUSIONS: Allergen-specific IL-4 producing cells in a peripheral blood
      mononuclear cell (PBMC) culture can be detected by ELISPOT and the response can
      synergistically be enhanced by suboptimal concentrations of PHA.

PMID- 9249275
TI  - Selective type IV phosphodiesterase inhibitors prevent IL-4-induced IgE
      production by human peripheral blood mononuclear cells.
AB  - BACKGROUND: Selective type IV phosphodiesterase (PDE) inhibitors elicit anti
      inflammatory and bronchodilatory activities in vitro and in vivo which suggest
      that these drugs could provide a new therapeutic approach for asthma treatment.
      OBJECTIVE: Regarding the role of IgE production in allergic and inflammatory
      reactions of the airways, we investigated the effect of selective PDE inhibitors
      on IL-4-driven IgE production by peripheral blood mononuclear cells (PBMC) or by
      purified B lymphocytes. METHODS: PBMC or purified B lymphocytes from non-allergic
      donors were stimulated for 13 days with IL-4 (100 U/mL) in the presence or in the
      absence of selective PDE inhibitors. IgE production is evaluated by an ELISA
      technique. RESULTS: The selective PDE IV inhibitors, rolipram and Ro 20-1724 (10
      microM), inhibit IL-4-induced IgE production by PBMC, but not by purified B
      lymphocytes. No modification of the IgE production was noted with the selective
      PDE III inhibitors, milrinone and SK&F 94-836, or the selective PDE V inhibitor,
      SK&F 96-231 (10 microM). Flow cytometry experiments showed that the effect of
      Rolipram could not be explained by the inhibition of the cell surface expression
      of the IL-4 receptor. Similarly, no significant effect of PDE IV inhibitors was
      observed on PHA-induced cell proliferation. The incubation of monocytes only with
      rolipram was sufficient to achieve a significant reduction of IgE production
      induced by IL-4. CONCLUSION: Taken together, these results indicate that PDE IV
      inhibitors reduce IL-4-induced IgE production by PBMC and suggest that the
      inhibition of IgE production could be explained by a failure of monocytes to
      provide the necessary costimulatory signals.

PMID- 9249276
TI  - Characterization of the allergen Der f 7 from house dust mite extracts by species
      specific and crossreactive monoclonal antibodies.
AB  - BACKGROUND: The group 7 mite allergens react with IgE in 50% of sera from
      allergic patients. OBJECTIVE: To determine the molecular and antigenic
      characteristics and heterogeneity of Der f 7 in mite extracts. METHODS:
      Monoclonal antibodies (MoAbs) produced from mice immunized with recombinant Der f
      7 were examined for crossreactivity to Der p 7 and then used for immunoblotting
      of 1 and 2-D gel electrophoresis. Deglycosylation was studied with N-glycosidase
      F and N-terminal sequencing by Edman degradation. The epitopes of the monoclonal
      antibodies were compared by cross-inhibitory immunoassays. RESULTS:
      Immunoblotting of D. farinae extracts with all the anti Der f 7 MoAbs showed
      major reactivities at 31, 30 and 25 kDa. The strongest immunostaining was at 25
      kDa which contrasted with Der p 7 where the 31 and 30 kDa bands were strongest.
      The relative strength of staining however varied between extracts. The 31 and 30
      kDa components were glycosylation products of the 25 kDa form which had the N
      terminal sequence predicted from cDNA analysis. Two MoAbs stained an 18 kDa band
      consistent with a degradation product. The 2-D gels showed that different
      components with pIs from 5.6-6.4. Both species-specific and Der p 7 crossreactive
      MoAbs were produced and a two-site ELISA assay for detecting group 7 allergen was
      developed with MoAbs recognizing different epitopes. CONCLUSIONS: Der f 7 has
      been defined by its natural N-terminal sequence and MoAbs. It apparently exists
      as different glycosylation and degradation products in mite extracts, the
      relative abundance of which differs with different preparations. A two-site ELISA
      to measure the allergen was developed.

PMID- 9249277
TI  - Detection, isolation and complete amino acid sequence of an aeroallergenic
      protein from rapeseed flour.
AB  - BACKGROUND: Seed proteins have been found to cause hypersensitivity by ingestion
      or inhalation. Rapeseed flour was responsible for allergic symptoms in a patient,
      who develops into allergy to mustard spice. OBJECTIVE: To determine the presence
      of allergenic proteins in rapeseed flour, and analyse the structure of the main
      component and its crossreactivity with the mustard allergen. METHODS: SDS-PAGE
      (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and subsequent
      immunoblotting with a serum from a rapeseed allergic patient were performed to
      detect IgE-binding proteins. Proteolytic digestions and high performance liquid
      chromatography were used to obtain the peptides from the allergenic BnIII napin
      from rapeseed flour. Automatic Edman degradations were carried out to determine
      their amino acid sequences, which were compared with other sequences in
      nucleotide and amino acid sequence databases. Crossreactivity assays were carried
      out by ELISA inhibition using sera from a rapeseed allergic patient and from
      patients allergic to mustard. RESULTS: The 2S albumins of rapeseed were
      recognized by the serum from a patient allergic to this seed. The most abundant
      isoform of the allergenic napins, BnIII, was used for structural and
      immunological analysis. The protein consists of two different chains of 9.5 and
      4.5 kDa. Their complete amino acid sequences were determined. The protein
      exhibited structural relationships with other napin-like storage proteins from
      seeds. IgE and IgG crossreactivity between rapeseed and mustard allergens was
      also demonstrated. Considering the structural and immunological data, certain
      polypeptide regions are suggested to be involved in the allergenicity of these
      proteins. CONCLUSIONS: Rapeseed contains 2S storage proteins which may cause
      allergy in hypersensitive individuals. These proteins exhibit great sequence
      similarity with 2S albumins from different seeds. Crossreactivity between mustard
      and rapeseed flours can be explained by sequence homology.

PMID- 9249278
TI  - Loss of nitric oxide release in passively sensitized guinea-pig aorta with
      purified immunoglobulin G1.
AB  - BACKGROUND: Vascular hyperresponsiveness can be reproduced by in vitro passive
      sensitization of isolated aorta with immunoglobulin G1 (IgG1) taken from
      ovalbumen-sensitized BFA guinea-pig. OBJECTIVE: The aim of the present work was
      to investigate the role of nitric oxide in the sensitization-induced alteration
      of the contractile and relaxant responses of guinea-pig aorta to noradrenaline
      (NA) and acetylcholine (ACh), respectively. METHODS: Cumulative concentration
      response curves to NA or ACh were established before and after IgG1 sensitization
      and then after successive treatments. RESULTS: IgG1 in vitro passive
      sensitization of aorta caused a significant hyperreactivity to NA and completely
      inhibited the relaxation to ACh. After sensitization, the addition of an intact
      aortic ring (with endothelium) in the organ chamber restored the maximal response
      to NA and ACh close to control but was ineffective in the presence of hemoglobin.
      The restoration of the control reactivity to NA was also inhibited in the
      presence of L-NAME or when the added aortic ring was endothelium-denuded.
      Moreover, L-arginine, a nitric oxide (NO) precursor, was able to restore the
      control reactivity to NA. CONCLUSION: The present results show that IgG1 in vitro
      sensitization induced a loss of NO release from the vascular endothelium. This
      loss of NO probably plays a great role in vascular hyperreactivity by increasing
      the contractile response and decreasing the relaxant response to mediators and
      would be a component of allergic diseases pathogenesis.

PMID- 9249279
TI  - The need for epidemiological studies.

PMID- 9249280
TI  - Contact sensitivity in pruritus vulvae: patch test results and clinical outcome.
AB  - BACKGROUND: Persistent vulval pruritus is common and may not be associated with
      signs of a primary vulval dermatosis. Patients with established vulval disease
      may develop contact sensitivity as a secondary problem after the application of
      topical therapy. OBJECTIVE: A retrospective study was performed to establish the
      prevalence of allergic contact dermatitis in patients with pruritus vulvae. In
      addition, the results of patch testing in women with vulval lichen sclerosus were
      compared with those in patients with primary pruritus vulvae and essential
      vulvodynia. METHODS: Over a 5-year period, 121 women with vulval problems were
      patch tested to the European Standard Series, selected preservatives, perfumes,
      local anesthetics, medicaments, and a vulval battery. RESULTS: Fifty-seven
      patients (49%) had one or more relevant allergic positive reactions. Medicaments
      or their constituents were the most common allergens to give reactions. Seven of
      the 16 patients (44%) with lichen sclerosus had positive reactions. Symptoms
      resolved or improved significantly in 67 patients (55.4%) overall. Six of the
      seven women with lichen sclerosus who had positive reactions noted an improvement
      in their symptoms. Patients who had a relevant allergy were much more likely to
      improve than those whose tests were negative (p < 0.001). CONCLUSION: Patients
      with pruritus vulvae and lichen sclerosus are at high risk of contact
      sensitivity. Patch testing is useful in the management of these patients and many
      can be helped by allergen avoidance.

PMID- 9249281
TI  - Path test reactions to the Chinese Standard Screening Allergens in 1,135 patients
      investigated for allergic contact dermatitis.
AB  - BACKGROUND: The patch test has become the standard method of investigating
      patients with allergic contact dermatitis. Many countries have developed standard
      screening allergens to make patch testing more efficient. A series of the Chinese
      Standard Screening Allergens were studied and modified. OBJECTIVE: This study
      investigated the frequency of contact allergies in suspected allergic contact
      dermatitis and tested the practicality of the Chinese Standard Screening Patch
      Test Allergens. METHODS: A total of 1,135 patients suspected of having allergic
      contact dermatitis were patch tested. Three hundred twelve (27.5%) were men, and
      their age ranged from 2 to 75 years old (mean age, 34.3 years), 823 (72.5%) were
      women, and their age ranged from 2 to 76 years old (mean age, 33.0 years).
      Nanjing Medical University supplied the Chinese Standard Screening Allergens and
      Finn-Chamber. All patients were patch tested according to the Chinese Standard
      Screening Patch Test Allergens with Finn-Chamber the protocol as established by
      the International Contact Dermatitis Research Group (ICDRG). RESULTS: From the
      1,135 patients suspected to have allergic contact dermatitis, 650 (57.3%) had at
      least one positive reaction. Nineteen (95%) of the Chinese Standard Screening
      Patch Test Allergens had positive reactions higher than 1%. Of 485 patients with
      negative reaction to the Standard Allergens, 106 patients were tested with other
      suspected contactants according to history. Thirty-nine (36.8%) had positive
      reactions to the contactants they provided. The total positive rate therefore
      increased by 3.4%. CONCLUSIONS: Our study results indicate that the Chinese
      Standard Screening Patch Test Allergens are suitable for use in routine clinic in
      China.

PMID- 9249282
TI  - Allergic contact dermatitis caused by Lithraea molleoides and Lithraea
      brasiliensis: identification and characterization of the responsible allergens.
AB  - BACKGROUND: Allergic contact dermatitis caused by species of Lithraea genus
      (Anacardiaceae) is frequent in South America. Nevertheless, it has been scarcely
      reported in the literature, hitherto the responsible allergens have not been
      studied in some species. OBJECTIVE: The purpose of this study was to identify and
      characterize the allergenic compounds of Lithraea molleoides and brasiliensis,
      and to investigate the existence of cross-reactions with Toxicodendron allergens.
      METHODS: Twenty-seven South American subjects (17 with previous Lithraea
      dermatitis and 10 controls without any plant dermatitis) and four North American
      subjects who are highly sensitive to poison oak were tested with both purified
      Lithraea molleoides and brasiliensis extracts and poison oak urushiol. Lithraea
      extracts were analyzed by gas liquid chromatography (GLC) and gas chromatography
      mass spectrometry (GC-MS). RESULTS: All 17 Lithraea-sensitive subjects reacted to
      poison oak urushiol and 13 of them also reacted to Lithraea molleoides and/or
      brasiliensis extracts. All 4 poison oak sensitive subjects reacted to poison oak
      urushiol and to Lithraea extracts. In both groups of sensitive subjects, the
      responses to poison oak urushiol were stronger and occurred at lower
      concentration than those to Lithraea extracts. The allergenic fraction in both
      Lithraea species consisted of: 3-pentadecylcatechol, 3-pentadecenylcatechol, 3
      heptadecenylcatechol and 3-hepta-dec-dienilcatechol. CONCLUSION: We concluded
      that Lithraea molleoides and brasiliensis allergens are closely related to
      urushiol, although their eliciting potential seems to be lower in comparison with
      poison oak urushiol, even for Lithraea-sensitive subjects.

PMID- 9249283
TI  - Treatment of poison ivy/oak allergic contact dermatitis with an extract of
      jewelweed.
AB  - BACKGROUND: Jewelweed (Impatiens biflora) is a plant which has been used for
      centuries for the treatment of poison ivy/oak allergic contact dermatitis.
      Numerous claims for its effectiveness exist in the lay press, and over-the
      counter medicaments containing jewelweed are reputed to be an effective remedy
      for poison ivy/oak dermatitis. Despite these claims, few scientific studies
      testing the effectiveness of jewelweed have been performed. OBJECTIVE: Our
      objective in this pilot study was to test the efficacy of an extract of jewelweed
      in the treatment of experimentally induced allergic contact dermatitis to poison
      ivy/oak. METHODS: A randomized, double-blinded, paired comparison investigation
      was performed. Ten adult volunteers were patch tested to urushiol, the allergenic
      resin in poison ivy/oak. For each volunteer, one patch test site was treated with
      an extract prepared from the fresh stems of jewelweed; the remaining site was
      treated with distilled water to serve as a control. Sites were examined on days
      2, 3, 7, and 9 with reactions graded on a numerical scale. RESULTS: All subjects
      developed dermatitis at each patch test site. There was no statistically
      significant difference in the objective scores at the sites treated with
      jewelweed extract versus the distilled water control sites. CONCLUSION: This
      study demonstrated that an extract of jewelweed was not effective in the
      treatment of poison ivy/oak allergic contact dermatitis.

PMID- 9249284
TI  - Value of patch testing in atopic dermatitis.
AB  - BACKGROUND: Because patients with atopic dermatitis are less prone to type IV
      allergies, there has been controversy regarding the role of patch testing in
      these patients. OBJECTIVE: The present study was conducted to evaluate the role
      of patch testing in atopic individuals. METHODS: One-hundred patients with hand
      eczema were patch tested using the standard patch test battery (HERMAL, Kurt
      Herrmann, Reinbek, West Germany) and the Finn chamber units. The total
      immunoglobulin class E (IgE) level was determined and correlated to the results
      of patch testing. RESULTS: Eighty-seven patients had positive patch test
      reactions. Among the 87 patients, 39 (44.8%) had atopic dermatitis. The most
      common allergens yielding positive results were nickel sulfate, 2.5%, (58.6%);
      potassium dichromate, 0.25% (56.3%); carba mix, 3%, (44.82%); formaldehyde, 1% in
      H2O, (40.22%); neomycin sulfate, 20%, (33.3%); and balsam of Peru 25%, (17.24%)
      respectively. Patients with atopic dermatitis were more frequently sensitive to
      neomycin sulfate than nonatopics. CONCLUSION: Patients with atopic dermatitis
      should be patch tested when indicated because they also develop contact allergic
      sensitization to a significant degree. Our observations indicate that patch
      testing with standard allergens often adds valuable information about contact
      sensitivity in these patients.

PMID- 9249285
TI  - Differential induction of cutaneous TNF-alpha and IL-6 by topically applied
      chemicals.
AB  - BACKGROUND: Increasing evidence shows that contact allergens and skin irritants
      can induce or upregulate the cutaneous expression of cytokines, including those
      that are required for the initiation of immune responses and which participate in
      inflammatory reactions. OBJECTIVE: The present investigation compared the ability
      of the skin allergens oxazolone and 2,4-dinitrochlorobenzene (DNCB) and the skin
      irritant benzalkonium chloride (BZC) to stimulate the cutaneous expression of
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in mice.
      RESULTS: Each chemical tested induced the dose-dependent production of IL-6 with
      similar kinetic profiles. BZC was less effective at provoking increases in this
      cytokine; concentrations (1%) that caused marked edema failed to stimulate
      significant changes in IL-6 expression. Under conditions of topical exposure in
      which each of these chemicals caused a vigorous inflammatory response in the
      skin, as measured by induced edema and the increased production of IL-6, only
      oxazolone and DNCB stimulated expression of TNF-alpha. The failure of BZC to
      initiate TNF-alpha production in the skin was not attributable to inhibition of
      the bioassay used to measure this cytokine and was apparently independent of the
      stimulation by this chemical of TNF-alpha inhibitory factors. CONCLUSION: These
      data indicate that not all chemicals that have the ability to cause skin
      irritation and cutaneous inflammation will elicit detectable TNF-alpha responses
      and that characterization of cutaneous irritants and allergens on the basis of
      induced cytokine expression patterns in the skin must be approached with caution.

PMID- 9249286
TI  - Contact sensitization to sunscreens.
AB  - BACKGROUND: Para aminobenzoic acid (PABA) derivatives and cinnamate are chemical
      sunscreens that protect against UVB (290 to 320 nm). They may occasionally
      produce contact and photocontact sensitization. OBJECTIVE: To report a
      sensitization to octyl-dimethyl-PABA and photosensitization to 2-ethylhexyl-p
      metossicinnamate in a 31-year-old man. METHODS: A patient with a 3-year history
      of a relapsing dermatitis involving the face, neck, legs, and knees is reported.
      The eruption had recurred every summer after sunlight exposure. Patch tests with
      International Contact Dermatitis Research Group (IC-DRG) standard series and the
      photopatch series (Hermal-Trolab, Reinbek, Germany) using Finn chambers on
      Scanpor (Norgesplaster A/S, Oslo, Norway) were carried out. RESULTS: We found a
      positive reaction to Balsam of Peru, fragrance mix, Escalol 507, and Parsol MCX
      (Hermal-Trolab, Reinbek, Germany). Photopatch test revealed a positive reaction
      only for Parsol MCX. CONCLUSION: The incidence of allergic contact dermatitis to
      sunscreens is considered low. Recently sunscreens patch test concentrations have
      been increased from 2% to 10%. These higher percentages will probably permit the
      identification of more cases of sunscreens allergy in the near future.

PMID- 9249287
TI  - Immediate and delayed skin allergy from cow dander.
AB  - BACKGROUND: Cow dander is the most common cause of occupational contact urticaria
      in Finland. Occasionally cow dander also causes allergic contact dermatitis,
      which can be revealed by patch testing with cow dander. OBJECTIVE: A patient with
      a combined type I and type IV allergy to cow dander is the subject of this
      report. RESULTS: She had intense pruritus, whealing, and severe dermatitis, but
      no respiratory symptoms. Skin tests and radioallergosorbent test indicated that
      she had both type I and type IV allergy to cow dander. CONCLUSION: Increasing
      numbers of cases with both type I and type IV allergy are reported, but the
      mechanism is not clear. In our clinic, we classify immediate reactions as contact
      urticaria if the clinical picture involves whealing, and as protein contact
      dermatitis if dermatitis dominates the clinical picture. If delayed allergic
      patch test results are obtained, we consider it allergic contact dermatitis.

PMID- 9249288
TI  - Allergic contact dermatitis caused by zinc pyrithione associated with pustular
      psoriasis.
AB  - A case of allergic contact dermatitis to a shampoo containing zinc pyrithione
      associated with an eruption of pustular psoriasis is reported. The patient had
      had stable psoriasis for 5 years, and never any other skin disease. Within 1 week
      she developed severe generalized pustular psoriasis with many lesions where the
      shampoo was applied. Treatment with cyclosporin, 200 to 300 mg daily, cleared the
      eruption within 4 weeks, except for psoriasis of the scalp. Extensive patch
      testing revealed a relevant sensitization to zinc pyrithione. This case
      illustrates that a generalized pustular psoriasis can be provoked by a substance
      present in a hair shampoo. Short-term treatment with cyclosporin is valuable in
      exacerbations of psoriasis caused by allergic contact dermatitis.

PMID- 9249289
TI  - Wrist dermatitis: contact allergy to neoprene in a keyboard wrist rest.
AB  - A case of allergic contact dermatitis to a keyboard wrist rest containing
      neoprene is reported. The patient, who had a history of sensitivity to rubber
      products, developed an acute vesicular reaction of the palmar aspects of her
      distal wrists, followed by eczematous patches of her extremities and face.
      Treatment with prednisone, a 3-week tapering dose (60, 40, 20 mg), cleared the
      dermatitis. The widespread uses of neoprene are discussed and suggest that
      neoprene will become a common source of contact dermatitis as the potential
      sources of exposure increase.

PMID- 9249290
TI  - Lymphomatoid contact dermatitis caused by nickel.
AB  - Lymphomatoid contact dermatitis is a rarely reported entity consisting of
      allergic contact dermatitis that resembles mycosis fungoides pathologically.
      Although the histopathology has been previously described, there have been no
      attempts to reproduce the dermatitis for pathologic evaluation. A 68-year-old
      woman presented with a papular rash on her neck after exposure to a nickel
      containing necklace. A biopsy specimen was suspicious for mycosis fungoides.
      However, the dermatitis responded quickly to topical steroids and avoidance of
      the necklace. A patch test to nickel was positive, and a biopsy specimen from the
      patch test site had no findings of mycosis fungoides. Although we were able to
      reproduce the contact dermatitis at a distant site, the disease was dissimilar.
      Lymphomatoid contact dermatitis has an excellent prognosis and resolves
      completely simply by avoiding the offending agent.

PMID- 9249291
TI  - Hairdresser's koilonychia.
AB  - Koilonychia is a nail disorder well known to accompany certain systemic diseases,
      but it can also be caused by external factors. We report two cases of
      occupational koilonychia in hairdressers caused by the toxic effect of chemicals
      used in permanent wave. Hairdresser's koilonychia has been seldom reported, but
      may be common.

PMID- 9249292
TI  - Occupational dermatitis transferred with job duties.
AB  - Astroemeria is an increasingly common cause of allergic contact dermatitis. We
      report a case of occupational contact dermatitis that was transferred with job
      duties. When advising patients about their risk, it is advisable to discuss the
      risk to others in the setting as well.

PMID- 9249293
TI  - Estimating dilutions for patch testing skin care products: a practical method.
AB  - When patch testing, it is helpful to patch test with the patient's own topical
      products. However, the thickness (viscosity) of the product often prevents easy
      measurement for dilution. A method of estimating volume: volume dilutions that
      requires minimal investment in supplies is presented. This method is only
      applicable to personal products and is not suitable for industrial or household
      chemicals.

PMID- 9249294
TI  - Betaxolol-associated hyperpigmentation of the fingers in a patient with unrelated
      contact dermatitis.
AB  - Betaxolol ophthalmic solution has been associated with periocular skin
      hyperpigmentation. We report a case of a woman with hyperpigmentation of the
      fingers associated with oral betaxolol. Based on case reports associated with the
      topical ophthalmic product, we believe the hyperpigmentation was likely caused by
      oral betaxolol.

PMID- 9249295
TI  - Allergic contact dermatitis from a wooden necklace.
AB  - A 36-year-old female kitchenworker twice developed eczematous lesions
      corresponding exactly to the area around her neck where she had worn a wooden
      necklace. Contact dermatitis lasted longer than 1 week. The necklace consisted of
      42 brown wooden beads and 63 other wooden parts, 0.5 to 3 cm diameter. Most parts
      could be identified as Cocobolo wood, Brazilian and East Indian rosewood, and
      teak. Patch tests with the pure constituents gave +3-reactions to three
      dalbergions and obtusaquinone, which are known to be the sensitizers of Cocobolo
      and the above-mentioned rosewoods. Because of these test results, the
      identification of the species by eye examination could be corroborated. Further
      detailed questioning revealed that the patient had played a recorder, probably
      made from Cocobolo (Dalbergia retusa), when a child, to which she unknowingly
      became allergic.

PMID- 9249468
TI  - Transient outward current contributes to Wenckebach-like rhythms in isolated
      rabbit ventricular cells.
AB  - Wenckebach-like rhythms in isolated rabbit ventricular cells are characterized by
      beat-to-beat increments in action potential duration (APD) and latency, giving
      rise to a beat-to-beat decrease in the recovery interval and culminating in a
      skipped beat. These systematic APD changes are associated with a beat-to-beat
      decrease in the slope of the early repolarizing phase (phase 1) of the action
      potential, which is partially controlled by the transient outward potassium
      current (Ito). When Ito is blocked with 4-aminopyridine, periodic Wenckebach
      rhythms are replaced by aperiodic Wenckebach rhythms, in which the beat-to-beat
      changes in the slope of phase 1 and in APD disappear but the beat-to-beat
      increase in latency remains. A beat-to-beat decrease in Ito, paralleling the beat
      to-beat changes in the slope of phase 1 and in APD, is seen in action-potential
      clamp experiments with Wenckebach rhythms previously recorded in the same cell.
      Simulations with an ionic model of Ito show cyclical changes in Ito consistent
      with the experimental data. These results demonstrate a key role for Ito in the
      generation of maintained periodic Wenckebach rhythms in isolated rabbit
      ventricular cells.

PMID- 9249470
TI  - Characterization of embryonic aortic impedance with lumped parameter models.
AB  - We systematically constructed and analyzed 18 analog circuit models to
      characterize embryonic arterial impedance. We measured simultaneous dorsal aortic
      pressure and flow, and we calculated experimental impedance in stage 24 chick
      embryos (n = 15). Cycle length was altered with thermal probes to improve
      frequency resolution of the impedance spectrum. Models were categorized according
      to the framework and the location of inductance and resistance terms. Models were
      excluded if they failed to reproduce the fundamental characteristics of the
      experimental impedance spectrum. We used weighted least-square parameter
      optimization to fit the model impedance curves to the experimental impedance
      data. Models that failed to converge parameters or revealed overparameterization
      were also excluded. We assessed goodness of fit in the frequency domain with the
      F-test, Akaike information criterion, and Schwarz criterion to determine the best
      fit model. The addition of a serial inductance term to the traditional three
      element windkessel model improved fit by reproducing modulus fluctuation and
      phase zero crossing (P < 0.001). Thus, despite dramatic differences in scale and
      geometry, the embryonic and mature vascular systems can be described using lumped
      parameter circuit models.

PMID- 9249469
TI  - SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with
      heart failure.
AB  - The purpose of this study was to examine the activity and expression of
      sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of
      dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue
      specimens were obtained from six normal (NL) control dogs and six dogs with
      chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential
      intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity
      was measured in isolated SR membrane fractions prepared from LV and RV
      myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal
      antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV
      and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs
      increased with increasing Ca2+ concentration and reached a plateau at 3 microM
      Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase
      activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01
      vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was
      unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms
      noncollagen protein) were also significantly lower in LV myocardium of HF dogs
      compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant
      differences in Ca(2+)-ATPase activity or expression were observed in RV
      myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase
      activity and protein levels are reduced in LV myocardium of dogs with chronic HF.
      This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+
      uptake and ultimately to Ca2+ overload and global LV dysfunction.

PMID- 9249472
TI  - Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to
      sympathetic nerve activity.
AB  - We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the
      dynamic sympathetic regulation of the cardiovascular system through the
      baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on
      the isolated carotid sinuses to evoke random changes in sympathetic nerve
      activity (SNA). We estimated the transfer functions from SNA to both aortic
      pressure (AoP) and heart rate (HR). The inhibition of NO synthesis by NG
      monomethyl-L-arginine (L-NMMA, 40 mg/ kg) altered neither the transfer function
      from SNA to AoP nor that from SNA to HR. In contrast, sodium nitroprusside (3-6
      micrograms.kg-1.min-1) significantly decreased the steady-state gain (40.3 +/-
      11.7% of the control, P < 0.05) of the transfer function from SNA to AoP without
      affecting the HR responses. We conclude that the basal release of NO may have a
      role in the tonic blood pressure regulation, whereas it may not be involved in
      the dynamic sympathetic regulation of AoP or HR through the baroreflex.

PMID- 9249471
TI  - Inflammatory cell-derived NO modulates cardiac allograft contractile and
      electrophysiological function.
AB  - We previously demonstrated that inhibition of inducible nitric oxide (NO)
      synthase (iNOS) ameliorated acute cardiac allograft rejection. This study used a
      rat cardiac transplant model to characterize contractile and electrophysiological
      dysfunction during early acute rejection, further examine the role of NO and iNOS
      in this process, and determine which cells expressed iNOS during early rejection.
      During early acute rejection, before significant myocyte necrosis, allograft
      papillary muscles had reduced tension development and rates of tension
      development and decline during beta-adrenergic, adenylate cyclase, and calcium
      stimulation compared with isograft and normals [e.g., tension of 36 (allograft)
      vs. 73 (isograft) mN/mm2 during calcium stimulation, P < 0.001]. Allografts had
      resting membrane potential depolarization and reduced action potential amplitude
      and upstroke velocity. iNOS mRNA was expressed in infiltrating inflammatory cells
      but not in allograft myocytes, endothelial cells, or isografts. Corticosteroids
      attenuated allograft contractile and electrophysiological dysfunction and
      inhibited iNOS enzyme activity. Direct iNOS inhibition with aminoguanidine
      inhibited NO production and prevented allograft contractile and
      electrophysiological dysfunction (e.g., tension of 64 mN/mm2 during calcium
      stimulation, P < 0.001). We conclude that 1) early allograft rejection caused
      contractile and electrophysiological dysfunction that was largely mediated by
      iNOS expression in infiltrating inflammatory cells, 2) corticosteroid-mediated
      amelioration of allograft contractile and electrophysiological dysfunction may
      reflect inhibition of iNOS, and 3) iNOS inhibition may offer an alternative in
      management of immune-mediated myocardial dysfunction.

PMID- 9249473
TI  - Role of ATP-sensitive K+ channels in ischemic preconditioning of skeletal muscle
      against infarction.
AB  - We studied the role and mechanism of ATP-sensitive K+ (KATP) channels in ischemic
      preconditioning (IPC) of skeletal muscle against infarction in vivo. Surgically
      denervated, noncontractile latissimus dorsi muscle flaps in pentobarbitone
      anesthetized pigs were assigned to nine groups: control; IPC (3 cycles of 10-min
      ischemia/reperfusion); preischemic lemakalim (LMK, 0.18 mg/muscle); postischemic
      LMK; sodium 5-hydroxydecanoate (5-HD, 27 mg/muscle) before IPC; glibenclamide
      (Glib 0.3 mg/kg iv) before IPC; 5-HD before preischemic LMK; 5-HD before
      ischemia; and Glib before ischemia. Except for Glib, all drugs were delivered to
      each muscle by 10-min local intraarterial infusion to avoid systemic effects. All
      muscle flaps underwent 4 h of global ischemia. Infarction was assessed at 48 h of
      reperfusion. In a separate study, muscle biopsies were taken before, during, and
      after ischemia for assay of high-energy phosphate and lactate contents and
      myeloperoxidase (MPO) activity. It was observed that muscle infarction in the IPC
      (24 +/- 2%) and preischemic LMK (21 +/- 2%) groups were smaller (P < 0.05) than
      that in the control (42 +/- 2%). The anti-infarction effect of IPC and LMK was
      blocked by 5-HD or Glib. IPC and preischemic LMK caused a higher (P < 0.05)
      muscle content of ATP and energy charge potential, a lower (P < 0.05) muscle
      content of lactate during ischemia, and a lower (P < 0.05) muscle MPO activity
      throughout 16 h of reperfusion compared with the control. These observations
      indicated for the first time that KATP channels are also involved in the anti
      infarction effect of IPC in noncontractile skeletal muscle in vivo. Presently,
      the cause and importance of energy-sparing and neutrophil-inhibitory effects of
      IPC and LMK are not known.

PMID- 9249474
TI  - Relationship between cardiac function and substrate oxidation in hearts of
      diabetic rats.
AB  - The effects of streptozotocin-induced diabetes on myocardial substrate oxidation
      and contractile function were investigated using 13C nuclear magnetic resonance
      (NMR) spectroscopy. To determine the consequences of diabetes on glucose
      oxidation, hearts were perfused with [1-13C]glucose (11 mM) alone as well as in
      the presence of insulin (to stimulate glucose transport) and dichloroacetate (to
      stimulate pyruvate dehydrogenase). The contribution of glucose to the
      tricarboxylic acid (TCA) cycle was significantly decreased in hearts from
      diabetic animals compared with controls, with glucose alone and with insulin;
      however, the addition of dichloroacetate significantly increased the contribution
      of glucose to the TCA cycle. Contractile function in hearts from diabetic animals
      was significantly depressed with glucose as the sole substrate, regardless of the
      presence of insulin or dichloroacetate (P < 0.0005). To determine whether
      diabetes had any direct effects on beta-oxidation and the TCA cycle, hearts were
      perfused with glucose (11 mM) plus [6-13C]hexanoate (0.5 mM) as substrates. In
      control hearts, with glucose plus hexanoate as substrates, hexanoate contributed
      98.9 +/- 2% of the substrate entering the TCA cycle; this was significantly
      decreased to 90.7 +/- 0.6% in the diabetic group (P < 0.02). The addition of
      hexanoate to the perfusate resulted in a significant increase in peak systolic
      pressure in the diabetic group (P < 0.001) such that contractile function was
      indistinguishable from controls.

PMID- 9249475
TI  - Adenosine stimulates nitric oxide synthesis in rat cardiac myocytes.
AB  - We investigated the effects of adenosine on nitric oxide (NO) synthesis by
      measuring the production of nitrite, a stable metabolite of NO, in cultured
      neonatal rat cardiac myocytes. Incubation of cultures with interleukin-1 beta (10
      ng/ml) for 24 h caused a significant increase in nitrite production. The
      interleukin-1 beta-induced nitrite production by cardiac myocytes was
      significantly increased by adenosine or its stable analog 2-chloroadenosine in a
      dose-dependent manner (10(-7)-10(-4) M). The adenosine A2-receptor antagonist KF
      17837 (10(-6) M), but not the A1-receptor antagonist 8-cyclopentyl-1, 3
      dipropylxanthine (10(-6) M), significantly inhibited 2-chloroadenosine-mediated
      nitrite production. The 2-chloroadenosine-induced nitrite production by
      interleukin-1 beta-stimulated cells was accompanied by inducible NO synthase mRNA
      and protein accumulation. In the presence of N6, 2'-O-dibutyryladenosine 3',5'
      cyclic monophosphate (cAMP) (10(-3) M) or isoproterenol (10(-5) M), interleukin-1
      beta-induced nitrite accumulation was further increased, but the effect of 2
      chloroadenosine was not additive or synergistic. The protein kinase C inhibitor
      calphostin C did not inhibit the effect of 2-chloroadenosine. These results
      indicate that adenosine acts on A2 receptors and augments NO synthesis in
      interleukin-1 beta-stimulated cardiac myocytes, at least partially through a cAMP
      dependent pathway.

PMID- 9249476
TI  - Circadian and ultradian control of cardiac output in spontaneous hypertension in
      rats.
AB  - The aim of the study was to test whether circadian and ultradian variations of
      cardiac output (CO) in spontaneously hypertensive rats (SHR) differ from those in
      normotensive Wistar-Kyoto rats (WKY). Twenty-four-hour beat-to-beat recordings of
      CO (by electromagnetic flow probe) and mean arterial pressure (MAP) were
      performed in the absence and presence of cardiac autonomic blockade with
      metoprolol and atropine methylnitrate. Ultradian variability was analyzed by
      spectral analysis on beat-to-beat data series (high-frequency range) and on
      averaged minute-to-minute data series (low-frequency range). In general,
      circadian and ultradian rhythms of CO were similar in SHR (n = 10) and WKY (n =
      9). Values of CO were high during the dark and low during the light period,
      whereas total peripheral resistance was highest during the light period. During
      cardiac autonomic blockade, relative differences between averaged values of CO
      over the dark and light periods were reduced. High-frequency spectral power of CO
      was mainly confined to fluctuations related to respiration and was not influenced
      by cardiac autonomic blockade. At low-frequency ranges, power spectra of CO
      lacked a dominant oscillator but showed 1/f characteristics. During cardiac
      autonomic blockade, low-frequency spectral power of CO fell without changing the
      1/f characteristics. These findings suggest that dynamic control of CO is not
      altered in SHR and that autonomic effects on CO are frequency dependent. In most
      frequency ranges, the relative variation of CO was higher than that of MAP. Thus,
      over 24 h in both adult SHR and WKY, MAP is controlled within a more narrow range
      than CO.

PMID- 9249478
TI  - CRE-like response element regulates expression of rat alpha 2D-adrenergic
      receptor gene in vascular smooth muscle.
AB  - Contractile and binding studies indicate that alpha 2-adrenergic receptors (ARs)
      are differentially expressed by vascular smooth muscle cells (SMCs) according to
      vascular segment (artery, arteriole, vein). In the present study, alpha 2D-AR
      mRNA was two- to threefold higher in vena cava than in aorta. To understand
      vascular regulation of alpha 2D-AR expression in these cells, we sequenced 2.8 kb
      of the 5' flanking region of the alpha 2D-AR gene. Notable features include two
      potential TATA boxes, an adenosine 3',5'-cyclic monophosphate response element
      (CRE)-like binding element, and an Sp1 element. Comparison of the rat and human
      genes revealed an overall homology of 74% over the 1.87-kb sequence 5' to the
      translation initiator methionine, including complete homology at the distal TATA,
      CRE-like, and Sp1 sites, alpha 2D-AR transcription starts from the guanine
      nucleotide 18 base pair downstream from the distal TATA box. Reporter gene
      constructs demonstrated strong alpha 2D-AR promoter activity, but with several
      differences in construct activity, in both rat aorta and vena cava SMCs. Analysis
      of an essential promoter fragment revealed two regions protected by aorta and
      vena cava SMC nuclear proteins. The core sequences of these protected regions are
      TGACGCTA and TATAA. The former CRE-like element conferred specific binding of
      both aorta and vena cava nuclear proteins. In addition, promoter activity was
      increased 300% by forskolin or 8-bromoadenosine 3',5'-cyclic monophosphate,
      indicating that the CRE-like element may regulate alpha 2D-AR expression in
      vascular tissue.

PMID- 9249477
TI  - Nitrovasodilators relax mesenteric microvessels by cGMP-induced stimulation of Ca
      activated K channels.
AB  - Nitric oxide (NO) released from endothelial cells or exogenous nitrates is a
      potent dilator of arterial smooth muscle; however, the molecular mechanisms
      mediating relaxation to NO in the microcirculation have not been characterized.
      The present study investigated the relaxant effect of nitrovasodilators on
      microvessels obtained from the rat mesentery and also employed whole cell and
      single-channel patch-clamp techniques to identify the molecular target of NO
      action in myocytes from these vessels. Both sodium nitroprusside (SNP) and S
      nitroso-N-acetylpenicillamine (SNAP) relaxed phenylephrine-induced contractions
      by approximately 80% but were significantly less effective in relaxing
      contractions induced by 40 mM KCl. Relaxation to SNP was also inhibited by the
      K(+)-channel blocker tetraethylammonium or by inhibition of the activity of the
      guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG). These
      results suggest that SNP stimulated K+ efflux by opening K+ channels via PKG
      mediated phosphorylation. Perforated-patch experiments revealed that both SNP and
      SNAP increased outward currents in microvascular myocytes, and single-channel
      studies identified the high-conductance Ca(2+)- and voltage-activated K+ (BKCa)
      channel as the target of nitrovasodilator action. The effects of
      nitrovasodilators on BKCa channels were mimicked by cGMP and inhibited by
      blocking the activity of PKG. We conclude that stimulation of BKCa-channel
      activity via cGMP-dependent phosphorylation contributes to the vasodilatory
      effect of NO on microvessels and that a direct effect of NO on BKCa channels does
      not play a major role in this process. We propose that this mechanism is
      important for the therapeutic effect of nitrovasodilators on peripheral
      resistance and arterial blood pressure.

PMID- 9249479
TI  - In vivo adaptive responses of the aorta to hypertension and aging.
AB  - To investigate the dynamic behavior of the aorta of freely moving rats during the
      maintenance of hypertension, a longitudinal study was performed in renal
      hypertensive (Goldblatt 1 kidney, 1 clip) rats aged 3, 6, and 9 mo in which
      hypertension was maintained for 1, 3, and 6 mo, respectively. The pulsatile
      caliber of the thoracic aorta was measured (electrolytic strain gauge chronically
      implanted) simultaneously with aortic pressure under basal conditions and during
      transient changes of blood pressure. Aortic thickness was determined postmortem
      by morphometry. Establishment of hypertension (179 +/- 5 mmHg) by increasing the
      stress developed by the aorta caused increases in the resting values of caliber
      (20%), thickness (21%), and strain (95%); the maintenance of hypertension for a 6
      mo period caused a further increase in thickness (58% vs. age-matched
      normotensive aortas) but not in aortic caliber and strain, the subsequent
      alterations of which were due only to growth/aging. Although different calibers,
      thicknesses, and dynamic strains were presented, the stress-strain relationship
      during transient blood pressure changes was similar for all hypertensive and
      normotensive groups with the exception of renal hypertensive rats aged 6 mo,
      which presented a steeper relationship (a large transitory increase in aortic
      distensibility was observed at that age). Dynamic adaptive responses of the aorta
      to hypertension compensate for geometric changes in such a way as to maintain a
      near-constant distensibility. It was concluded that, in contrast to the
      extrathoracic vessels, the adaptive responses of the aorta to hypertension were
      directed to maintain its compliance without changing the distensibility and
      stress-strain relationship, contributing to partially counterbalance the
      increased pressure and the decreased compliance of the more peripheral components
      of the arterial tree.

PMID- 9249480
TI  - Endothelial ATP-sensitive potassium channels mediate coronary microvascular
      dilation to hyperosmolarity.
AB  - Coronary arterial occlusion has been shown to increase osmolarity in the
      myocardial interstitium. Intracoronary injection of hyperosmolar solutions
      reduces coronary vascular resistance. However, the response of coronary
      microvessels to an abluminal increase in osmolarity is unclear, and the
      underlying mechanism for its vasomotor regulation has not been elucidated. In
      this regard, porcine coronary arterioles (81 +/- 2 microns) were isolated,
      cannulated, and pressurized for in vitro study. Hyperosmolarity (300-345 mosM)
      was produced by adding D-glucose or D-sucrose to the extravascular solution.
      After the arterioles developed a stable vascular tone, a graded vasodilation was
      observed when glucose or sucrose was incrementally administered. This
      hyperosmotic vasodilation was abolished after endothelial removal. Intraluminal
      administration of KCl (80 mM) or the ATP-sensitive potassium (KATP)-channel
      inhibitor glibenclamide (1 microM) to the intact vessels significantly attenuated
      the hyperosmotic vasodilation. Inhibition of inward rectifier potassium channels
      by a low concentration of BaCl2 (10 microM) did not affect vasodilation. However,
      a high concentration of BaCl2 (100 microM), which has been reported to inhibit
      KATP channels, attenuated the hyperosmotic vasodilation. Iberiotoxin (100 nM), a
      calcium-activated potassium (KCa)-channel inhibitor had no effect on
      hyperosmolarity-induced vasodilation. Inhibition of the synthesis of endothelial
      nitric oxide, prostaglandins, and arachidonic acid metabolites from cytochrome P
      450 had no effect on hyperosmotic vasodilation. Furthermore, inhibition of
      vascular smooth muscle KATP channels and the large- and small-conductance KCa
      channels by extraluminal administration of glibenclamide, iberiotoxin, and
      apamin, respectively, did not alter vasodilation in response to hyperosmolarity.
      These results indicate that dilation of coronary arterioles in response to
      hyperosmotic stimulation requires an intact endothelium. However, the response is
      independent of the release of nitric oxide, prostaglandins, or cytochrome P-450
      related endothelium-derived hyperpolarizing factor and is not a result of
      activation of KATP and KCa channels in vascular smooth muscle. It is suggested
      that the opening of KATP channels in vascular endothelium and subsequent
      hyperpolarization of that cell type mediate coronary microvascular dilation in
      response to hyperosmolarity.

PMID- 9249481
TI  - Humoral factor(s) produced by pressure overload enhance cardiac hypertrophy and
      natriuretic peptide expression.
AB  - Chronic pressure overload is known to increase cardiac mass and expression levels
      of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      mRNAs. Although mechanical stretching of cardiac myocytes could cause these
      changes, humoral factor(s) secondary to pressure overload may also be involved.
      To dissociate humoral effects from the effects of mechanical loading on cardiac
      hypertrophic responses, we examined expression of ANP and BNP at both mRNA and
      protein levels and proportions of myosin isoforms in transplanted cervical hearts
      that were mechanically unloaded under conditions with or without hypertension by
      aortic coarctation. Seven days after transplantation, cardiac atrophy that
      usually occurs in transplanted hearts without hypertension by coarctation was
      prevented in the transplanted hearts with hypertension by coarctation. The levels
      of expression of ANP and BNP mRNAs were increased in the transplanted hearts with
      relative to those without hypertension by coarctation. The plasma level of
      angiotensin II was higher in rats with than without hypertension by coarctation.
      Plasma endothelin-1 levels were not significantly different between the two
      groups. In addition, levels of expression of ANP and BNP mRNAs were increased in
      the transplanted hearts without hypertension relative to those in the in situ
      hearts. The proportion of the V3 myosin isoform was also increased in the
      transplanted hearts without hypertension relative to the in situ hearts. These
      results indicate that humoral factor(s) secondary to the pressure overload
      produced by aortic coarctation enhanced the cardiac hypertrophic response and
      elevated the levels of mRNAs encoding these embryonic markers. Moreover, our
      findings regarding ANP and BNP expression in the transplanted hearts provide
      additional evidence that the fetal genes are reexpressed during the process of
      cardiac atrophy as well as in cardiac hypertrophy.

PMID- 9249482
TI  - Negative chronotropic and inotropic effects of endothelin isopeptides in
      mammalian cardiac muscle.
AB  - In isolated rabbit right atria, endothelin (ET) isopeptides ET-1 and ET-3
      elicited a concentration-dependent negative chronotropic effect (NCE) in the
      presence of isoproterenol (Iso): ET-1 was approximately 10 times more potent than
      ET-3. The NCE of ET-1 was abolished by the ETA- and ETB-receptor antagonist TAK
      044 (1 microM) or the ETA-receptor antagonist BQ-123 (10 microM), but it was not
      affected by the ETB-receptor antagonist RES-701-1 or BQ-788. ET-1 decreased the
      adenosine 3',5'-cyclic monophosphate (cAMP) level in the presence of Iso in
      rabbit atria. Pretreatment with pertussis toxin (PTX) markedly attenuated the NCE
      of ET-1 and abolished the decrease in the cAMP level induced by ET-1. In isolated
      dog ventricular trabeculae, ET-1 elicited a pronounced negative inotropic effect
      (NIE), whereas ET-3 induced a small but significant positive inotropic effect in
      the presence of Iso. The NIE was abolished by the ETA-receptor antagonist BQ-123
      (1 microM) and partially attenuated by the ETB-receptor antagonist RES-701-1. The
      positive inotropic effect of ET-3 was abolished by RES-701-1. Although
      pretreatment with PTX markedly attenuated the NIE of ET-1, cAMP levels in dog
      ventricular muscle were not decreased by ET-1. These results indicate that
      activation of an ETA receptor that is coupled to the PTX-sensitive G protein
      plays a dominant role in the NCE and NIE of ET-1. The NCE of ET-1 may, in part,
      be due to a decrease in cAMP level. By contrast, the NIE of ET-1 does not involve
      an alteration of cAMP accumulation. The present findings imply that ET
      isopeptides might antagonize the cardiostimulatory action of catecholamines
      mediated by beta-adrenoceptors when the blood level of both endogenous regulators
      are increased under cardiovascular pathophysiological situations.

PMID- 9249483
TI  - Ca2+ permeation through Na+ channels in guinea pig ventricular myocytes.
AB  - This study was undertaken to test the hypothesis that, in the absence of
      extracellular Na+, Ca2+ can permeate tetrodotoxin (TTX)-sensitive Na+ channels in
      Cs(+)-loaded whole cell voltage-clamped guinea pig ventricular myocytes (22-24
      degrees C). With 10 mM extracellular Ca2+, 50-ms step depolarizations (-50 to +25
      mV) from holding potentials of -100 or -80 mV elicited fast and slow types of
      inward current: 1) a small (< 400 pA) dihydropyridine-insensitive inward current
      that exhibited similar voltage dependence to that of Na+ channels, with an
      activation threshold and peak near -45 mV and -30 mV, respectively; and 2) a
      larger and slower L-type Ca2+ current that activated and peaked at more positive
      potentials. Extracellular replacement of Ca2+ by Mg2+ abolished both currents.
      The lack of sensitivity of the low-threshold Ca(2+)-current amplitude to 50 or
      200 microM Ni2+ suggests that this current is not produced by T-type Ca2+
      current. In contrast, TTX dose dependently inhibited the low-threshold Ca2+
      current, with a half-maximal inhibition concentration of 2.4 microM. Veratridine
      (10-50 microM), a plant alkaloid that alters the gating and permeability
      properties of Na+ current, induced an outward shift of time-dependent current
      during steps to -25 mV and typical slowly decaying inward tail currents after
      repolarization to -80 mV. Cell exposure to 10 and 50 microM extracellular Na+
      inhibited the inward current by 21.2 +/- 3.9% (n = 23) and 14.0 +/- 3.0% (n =
      14), respectively, whereas 1 microM Na+ (n = 14) was without effect. The
      application of 200 microM Na+ produced a small enhancement of the current (+6.2
      +/- 4.1%; n = 14) which was just at the limit of significance. Our data support
      the notion that Ca2+ can permeate cardiac Na+ channels in the absence of an
      agonist and external Na+.

PMID- 9249484
TI  - Constitutive expression of ICAM-1 in rat microvascular systems analyzed by laser
      confocal microscopy.
AB  - The present study aimed to demonstrate constitutive expression of the
      intercellular adhesion molecule (ICAM)-1 among arterioles, capillaries, and
      venules in the mesentery and liver and to examine the interaction between
      cultured endothelial cells and leukocytes in rats. ICAM-1 expression in the
      microvessels in vivo was visually demonstrated by laser confocal fluorescence
      microscopy. A monoclonal antibody against rat ICAM-1 (1A29) was labeled with
      fluorescein isothiocyanate, and the binding ratio between the fluorescence and
      immunoglobulin was determined for data calibration. Intravascularly administered
      fluorescein isothiocyanate-labeled 1A29 was distributed heterogeneously among the
      hierarchy of microvessels in the mesentery: postcapillary venules were the major
      portion expressing ICAM-1 constitutively, and the density of 1A29 bound to their
      endothelium was at least 10 times higher than that in true capillaries and
      arterioles in the same mesentery. On the other hand, the liver expressed ICAM-1
      abundantly in sinusoids to the extent similar to that in central venules. These
      results suggest that postcapillary venules serve as an active gateway with the
      readiness to help adhere circulating leukocytes exposed to proinflammatory
      stimuli in acute inflammation.

PMID- 9249485
TI  - Effects of hibernation on neural and endothelial control of mesenteric arteries
      of the golden hamster.
AB  - The effects of hibernation on mesenteric arterial innervation and function were
      examined using pharmacological and immunohistochemical techniques in age-matched
      controls, cold-exposed controls, and 4-wk-hibernated golden hamsters. Electrical
      field stimulation of the isolated mesenteric arterial bed elicited frequency
      dependent vasoconstriction. The sensitivity of responses was significantly
      increased in tissues from hibernating animals compared with cold-exposed
      controls. Vasoconstrictor responses to exogenous norepinephrine were also
      increased in hibernation. However, there was a significant decrease in
      sensitivity of vasoconstriction to ATP in hibernated and cold-exposed tissue
      compared with age-matched controls. In preparations preconstricted with
      methoxamine, endothelium-dependent vasodilator responses to acetylcholine and ATP
      were similar among the groups. Immunohistochemical investigation of mesenteric
      arteries revealed no differences among the groups in density of innervation by
      nerves immunoreactive for tyrosine hydroxylase, neuropeptide Y, and calcitonin
      gene-related peptide. Postjunctional changes appear to occur in hibernation,
      leading to augmentation of sympathetic vasoconstriction, which is consistent with
      the increase in peripheral vascular resistance in hibernation. Endothelium
      dependent vasodilatation is not significantly changed in hibernation in the
      hamster mesenteric arterial bed.

PMID- 9249486
TI  - Coactivation of resistance vessels and muscle fibers with acetylcholine release
      from motor nerves.
AB  - Acetylcholine (ACh) released at the neuromuscular junction (NMJ) triggers muscle
      fiber contraction. We tested whether this source of ACh also triggers
      vasodilation. Arterioles [diameter: 4th order (4A), 18 +/- 3 microns; 2nd order
      (2A), 35 +/- 2 microns] and feed arteries (60 +/- 4 microns) were observed in
      retractor muscle of anesthetized hamsters. During stimulation [25% duty cycle
      (500-ms train, 1 per 2 s) at approximately 40% of maximum isometric tension], a
      nicotinic receptor antagonist (tubocurarine, 10 microM) prevented contraction,
      yet 2A and 4A arterioles and feed arteries rapidly (< or = 5 s) dilated (by 9 +/-
      2, 11 +/- 3, and 8 +/- 1 microns, respectively; P < 0.05); neither cholinergic
      innervation of the vasculature nor ACh release from endothelium was apparent.
      Vasodilator responses doubled (P < 0.05) with cholinesterase inhibition (eserine,
      1 microM) and were abolished with muscarinic receptor antagonism (atropine, 10
      microM). Microiontophoresis of ACh onto arterioles triggered vasodilation that
      conducted into feed arteries, confirming functional continuity between
      intramuscular and extraparenchymal resistance vessels. To determine whether ACh
      served as a vasodilator during exercise, vascular responses to muscle contraction
      were measured in the presence or absence of atropine. With 2.5% duty cycle (50
      ms, 1 per 2 s), atropine attenuated vasodilation by 35% in 2A and 51% in 4A
      arterioles and by 65% in feed arteries. With 25% duty cycle, arteriolar dilation
      was unaffected by atropine, yet feed artery dilation was attenuated by 60%; this
      was accompanied by a 50% reduction in functional hyperemia. Our findings indicate
      that ACh "spillover" from NMJs can coactivate muscarinic receptors, giving rise
      to a dilation that is conducted into feed arteries. This ascending vasodilation
      is integral to the full expression of functional hyperemia.

PMID- 9249488
TI  - Calcium and mechanotransduction of the myogenic response.
AB  - The purpose of this study was to measure vascular smooth muscle (VSM) cytosolic
      calcium ([Ca2+]i) during the myogenic response. We examined the temporal and
      steady-state relationships between lumen diameter and VSM [Ca2+]i in isolated
      arterioles exposed to step changes in intravascular pressure. We also studied the
      relationship between step sizes in intravascular pressure and changes in [Ca2+]i.
      First-order arterioles from the hamster cheek pouch were isolated, cannulated,
      and pressurized. [Ca2+]i was quantified using the ratio of emitted fluorescence
      intensity (R340/380) during alternate excitation of fura 2-loaded vessels at 340
      and 380 nm. Stepwise increases in transmural pressure elicited corresponding
      increases in steady-state [Ca2+]i and myogenic constriction. From a common
      baseline pressure, the initial rise in [Ca2+]i after a step change in pressure
      was directly related to the magnitude of the step size and of the distension
      caused by that pressure step. This supports the theory that there is a
      relationship between the initial distension of the vessel and the initial [Ca2+]i
      change. Also, increasing the size of the step change in pressure resulted in a
      greater myogenic response, yet no difference in the steady-state [Ca2+]i was
      detected, which suggests that Ca2+ is not the principal or only determinant of
      steady-state constriction. Finally, larger increases in [Ca2+]i do not
      necessarily augment the myogenic response, which suggests that some minimal rise
      in [Ca2+]i is required to elicit myogenic vasoconstriction. Collectively, these
      data suggest the presence of a separate, Ca(2+)-independent regulatory system.

PMID- 9249487
TI  - Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase
      hypotension.
AB  - We tested the concept that tumor necrosis factor-alpha (TNF-alpha) or platelet
      activating factor (PAF) mediated Escherichia coli endotoxin lipopolysaccharide
      (LPS)-induced upregulation of nitric oxide (NO) and acute-phase hypotension (APH)
      in the rat. LPS (0.5 mg/kg i.v.) given to rats treated with saline or nonimmune
      goat-derived gamma-globulin (immunoglobulin G, 22 mg/kg i.m.) produced APH and
      increased plasma concentrations of TNF-alpha and nitrate and nitrite anions
      (reactive nitrogen intermediates; RNI) and NO in ex vivo incubates of
      polymorphonuclear neutrophils (PMN) and inducible NO synthase (iNOS) mRNA in PMN.
      Pretreatment of rats with a polyclonal TNF-alpha antibody (TNF-Ab, 22 mg/kg i.m.)
      abolished LPS-mediated increases in plasma TNF-alpha but failed to inhibit APH or
      the NO system. TNF-alpha (8.2 micrograms/kg i.v.) produced transient hypertension
      and sustained tachycardia and increased plasma TNF-alpha and PMN iNOS mRNA but
      not RNI. LPS and TNF-alpha decreased spontaneous and calcimycin (Ca2+ ionophore,
      1 microM)- and PAF (1 microM)-mediated increases in head-space NO production by
      rings of mesenteric artery incubated ex vivo. TNF-Ab abolished all effects of TNF
      alpha. PAF (25, 50, and 100 ng/kg) produced APH without increasing plasma TNF
      alpha, RNI, or PMN iNOS mRNA. The PAF receptor antagonist BN-50730 (80
      micrograms/kg i.v.) abolished PAF-induced APH and attenuated LPS-induced
      increases in RNI. We conclude that 1) LPS produces parallel but unrelated changes
      in TNF-alpha and RNI in plasma and PMN during the APH of endotoxemia; and 2)
      endogenous TNF-alpha is not required for LPS-mediated induction of iNOS mRNA, and
      PAF mediates LPS-induced APH.

PMID- 9249489
TI  - Relationship between external load and isolated myocyte contractile function with
      CHF in pigs.
AB  - Past studies have demonstrated that the negative relationship between afterload
      and contractile performance of papillary muscles is shifted downward and to the
      left with the development of hypertrophy. However, it remained unclear whether a
      similar load-contractility relationship could be constructed for isolated
      myocytes, particularly with the development of congestive heart failure (CHF).
      Accordingly, the effect of incrementally increased external loads on the
      contractile performance of left ventricular (LV) myocytes isolated from pigs in
      the normal state (n = 5) and after the development of chronic supraventricular
      tachycardia (SVT)-induced CHF (SVT-CHF; 240 beats/min, 3 wk; n = 5) was examined.
      This study used precalibrated microspheres to impose a quantifiable load on
      isolated myocytes, and myocyte contractility was assessed by videomicroscopy.
      Steady-state unloaded extent of shortening was 5.4 +/- 0.2 microns in control
      myocytes (n = 80) and was significantly reduced in the myocytes with the
      development of SVT-CHF (4.4 +/- 0.2 microns, n = 93; P < 0.05). Inverse
      relationships between relative resistive load and myocyte contractile function
      were observed at both normal and CHF states (r2 > 0.85). For myocyte velocity of
      shortening, the slope of this relationship was significantly reduced in the SVT
      CHF state compared with controls (-46.3 x 10(-6) and -34.6 x 10(-6)
      microns3.microN-1.s-1, respectively; P < 0.05). At higher relative resistive
      loads (> 0.18 x 10(-6) microN/microns2), the reduction in myocyte shortening
      extent under an equivalent relative resistive load was significantly greater in
      the SVT-CHF myocytes compared with controls (62.8 +/- 3.9 vs. 45.6 +/- 4.7%,
      respectively, P < 0.05). The present study demonstrated for the first time that a
      load-dependent relationship can be derived for intact isolated LV myocytes in
      both normal and CHF states. The defect in the capacity of SVT-CHF myocytes to
      respond to an increased relative resistive load is a likely contributory
      mechanism for the LV pump dysfunction that occurs in this model of CHF.

PMID- 9249490
TI  - Calcium handling by sarcoplasmic reticulum of neonatal swine cardiac myocytes.
AB  - In recent years, because of similarities to human infants, neonatal piglets have
      increasingly become the model of choice for studying neonatal heart function.
      However, the cardiac sarcoplasmic reticulum (SR) has not been thoroughly
      characterized in this species. Accordingly, Ca2+ pump kinetics, efflux channel
      characteristics, Ca2+ transients, and contractile movements were examined in
      isolated newborn piglet cardiac ventricular myocytes. Maximum uptake rate (Vmax)
      and concentration required to produce a half-maximal effect (K0.5) for oxalate
      supported, ATP-dependent 45Ca2+ uptake by the SR of digitonin-lysed myocytes were
      285 +/- 17 nmol 45Ca2+.min-1.mg-1 and 0.69 +/- 0.07 microM, respectively. In the
      absence of phospholamban phosphorylation, Vmax was reduced to 195 +/- 26 nmol
      45Ca2+.min-1.mg-1 (P < 0.05 vs. control) and K0.5 increased to 1.28 +/- 0.13
      microM (P < 0.05 vs. control). [3H]ryanodine binding studies yielded a maximum
      binding capacity of 181 +/- 12 fmol/mg and a dissociation constant of 1.7 +/- 0.2
      nM. Raising extracellular Ca2+ (0.5-5 mM) increased peak amplitude and decreased
      the duration of electrically stimulated fura 2 Ca2+ transients and recordings of
      cell length changes. Both ryanodine and 2,5-di-tert-butylhydroquinone, an
      inhibitor of SR calcium adenosinetriphosphatase, completely abolished Ca2+
      transients in piglet myocytes. These studies indicate that the SR has a
      significant role in excitation-contraction coupling in neonatal piglet myocytes.

PMID- 9249491
TI  - Low-dose prostacyclin has potent capillary permeability-reducing effect in cat
      skeletal muscle in vivo.
AB  - The dose-response effects of intravenous infusion of prostacyclin on capillary
      permeability (the capillary filtration coefficient technique), hydrostatic
      capillary pressure, transcapillary filtration, and vascular tone were analyzed in
      vivo on cat skeletal muscle from a normal and an increased permeability level.
      Increased permeability was accomplished by intra-arterial infusion of tumor
      necrosis factor-alpha or histamine. Permeability effects of bradykinin were also
      analyzed. Prostacyclin decreased capillary permeability by 8% at a dose of 0.1
      ng.kg-1.min-1 and at most by 30% below control attained at 2 ng.kg-1.min-1, also
      with no effect on vascular tone and hydrostatic capillary pressure. The
      permeability increase by tumor necrosis factor-alpha and histamine (by 54 and
      73%) was more than counteracted by the simultaneous infusion of prostacyclin at 2
      ng.kg-1.min-1. The vasodilator effect of tumor necrosis factor-alpha was also
      restituted. Indomethacin (prostacyclin inhibitor)-induced increase in capillary
      permeability (25%) was more than restituted by prostacyclin at 2 ng.kg-1.min-1.
      Surprisingly, bradykinin decreased capillary permeability. We conclude that
      endogenous prostacyclin may be a physiological regulator of capillary
      permeability and that low-dose prostacyclin infusion may have clinical relevance
      in states of increased permeability.

PMID- 9249493
TI  - Myocardial temperature in acute myocardial infarction: protection with mild
      regional hypothermia.
AB  - This study tests the hypothesis that a 2-4 degrees C reduction in myocardial
      temperature, obtained by using topical regional hypothermia (TRH), reduces
      infarct size. Anesthetized rabbits received coronary artery occlusion and
      reperfusion. We cooled hearts in the TRH group by applying an ice bag directly
      over the risk zone; the control group received no intervention. Risk zone
      myocardial temperature (MT) in the TRH group was reduced at occlusion by 2
      degrees C from baseline and after 5 min of occlusion by 3.6 degrees C. In the
      control group, MT in the risk region remained within 0.3 degree C of baseline.
      The ischemic area was similar in both groups, yet infarct size in the TRH group
      was reduced by an average of 65% compared with the control group. Infarct size
      closely correlated with MT in the risk region at the time of occlusion. In a
      second protocol in which all hearts were paced, infarct size was 21% of the risk
      region in TRH hearts compared with 44% in controls. These results strongly
      support the important role of MT in the progression of necrosis and demonstrate
      that the application of local cooling to the risk region profoundly reduces
      myocardial infarct size.

PMID- 9249494
TI  - Plasma renin activity in heart failure-prone SHHF/Mcc-facp rats.
AB  - Plasma renin activity (PRA) increases during heart failure; however, PRA is
      altered by drug therapy, and it is difficult to study the natural progression of
      elevated PRA in humans and the possible factors that contribute to its rise. This
      study evaluated PRA in a drug-naive hypertensive rat model (SHHF/Mcc-facp) that
      has a genetic program resulting in heart failure (HF). Mean arterial blood
      pressure and PRA were determined and correlated to heart weight index in
      conscious normotensive, spontaneously hypertensive rats and HF rats of various
      ages. PRA, atrial natriuretic peptide, and aldosterone levels progressively
      increase with age in male HF rats. PRA and blood pressure are independently
      correlated to cardiac hypertrophy in male HF rats. Atrial natriuretic peptide was
      elevated in spontaneously hypertensive compared with normotensive rats. Female HF
      rats have elevated PRA, but the increase is temporally delayed compared with that
      in male HF rats. Hypertension, PRA, and male gender are independent factors
      contributing to cardiac hypertrophy and heart failure in the HF model. The HF rat
      model may prove useful in determining the contribution of these factors in the
      progression from cardiac hypertrophy to heart failure.

PMID- 9249492
TI  - Mechanism of enhancement of slow delayed rectifier current by extracellular
      sulfhydryl modification.
AB  - To explore the role of sulfhydryl (SH) groups in the function of cardiac slow
      delayed rectifier channels, we tested the effects of extracellular thimerosal
      (TMS, a hydrophilic SH modifier) on slow delayed rectifier current (IKs) induced
      by human IsK (hIsK) in oocytes and on the native IKs in canine ventricular
      myocytes. TMS (25 or 50 microM) had similar effects on the two currents: current
      amplitude increased, and there was an acceleration of activation and a slowing of
      deactivation. These effects showed little or no reversal after washout of TMS.
      The effects did not depend on intracellular Ca release or protein kinase
      activities but could be suppressed by dithiothreitol pretreatment. According to
      the current model of transmembrane topology, there is no cystein in the
      extracellular domain of hIsK. A likely candidate for TMS modification is the SH
      group on another subunit in oocyte cell membrane that interacts with IsK to form
      a functional channel. To explore the domain of hIsK involved in the interaction,
      extracellular serines of hIsK were mutated to cysteines at three locations: S37C
      (close to the transmembrane domain), S4C (close to the NH2-terminus), and S28C
      (in between). S37C and S28C mutations did not affect channel properties or hIsK
      response to TMS. On the other hand, S4C mutation reduced current expression even
      when S4C cRNA was injected at a quantity 50-fold higher than that of the other
      three proteins. Importantly, the response to TMS was markedly reduced in S4C
      compared with the other three proteins. Therefore, the NH2-terminus of hIsK may
      be involved in hIsK interaction with the SH-bearing subunit, and this interaction
      modulates slow delayed rectifier channel function.

PMID- 9249495
TI  - NO-containing factors mediate hindlimb vasodilation produced by superior
      laryngeal nerve stimulation.
AB  - The electrical stimulation (ES) of the superior laryngeal nerve (SLN) produces
      reflex vasodilation in the rat hindlimb. This study determined whether this
      vasodilation is mediated by the release of nitric oxide (NO)-containing factors
      (NOF) from NO synthase (NOS)-positive postganglionic lumbar sympathetic fibers
      that innervate the rat hindlimb vasculature. ES of the SLN (1-10 Hz for 15 s)
      produced frequency-dependent reductions in mean arterial blood pressure (MAP) and
      hindlimb and mesenteric (MR) vascular resistances. The hindlimb vasodilation was
      not observed in rats in which the lumbar sympathetic trunk was transected 7-10
      days previously. The falls in hindquarter vascular resistance (HQR) produced by
      lower intensity ES of the SLN were virtually abolished by the specific inhibitor
      of neuronal NOS 7-nitroindazole (7-NI, 45 mg/kg i.v.). The fall in HQR produced
      by 10 Hz ES of the SLN was not affected by 7-NI. The falls in MR produced by 1-10
      Hz ES of the SLN were unaffected by 7-NI. Four consecutive episodes of ES at 10
      Hz produced pronounced and equivalent reductions in MAP, HQR, and MR. After
      administration of 7-NI, the first ES produced similar hemodynamic responses to
      those observed before injection. However, each subsequent ES produced
      progressively and markedly smaller falls in HQR, whereas each episode of ES
      produced similar falls in MR. These results suggest that the reflex vasodilation
      in the rat hindlimb produced by ES of the SLN involves the release of newly
      synthesized and performed stores of NOF from NOS-positive postganglionic lumbar
      sympathetic nerves.

PMID- 9249496
TI  - ANP protects against reoxygenation-induced hypercontracture in adult
      cardiomyocytes.
AB  - It was investigated whether atrial natriuretic peptide (ANP) or the related
      peptide urodilatin can be used for protecting cardiomyocytes against
      reoxygenation-induced hypercontracture. Isolated ventricular cardiomyocytes (from
      adult rats) were used as the experimental model. When the cells were submitted to
      substrate-free anoxia (135 min) and subsequent reoxygenation (30 min), the onset
      of reoxygenation provoked their hypercontracture. It was studied whether the
      temporary presence of ANP or urodilatin (1 nM to 1 microM) or 8-bromo-guanosine
      3',5'-cyclic monophosphate (8-BrcGMP; 1 microM to 1 mM) during the last 15 min of
      anoxia and the first 15 min of reoxygenation prevented hypercontracture. It was
      found that ANP (1 microM) prevented hypercontracture in 82 +/- 8% (SD),
      urodilatin (1 microM) in 80 +/- 9%, and 8-BrcGMP (1 mM) in 72 +/- 10% of the
      cells (n = 40 cells). When ANP (1 microM) was added during the last 15 min of
      anoxia and the first 15 min of reoxygenation, the cellular concentration of cGMP
      increased from 0.41 +/- 0.04 to 2.80 +/- 0.81 pmol/mg protein (n = 6 cultures).
      The results show that the reoxygenation-induced hypercontracture in
      cardiomyocytes can be attenuated by the temporary presence of the stimulators of
      particulate guanylate cyclase, ANP or urodilatin.

PMID- 9249497
TI  - Inhibition of the voltage-dependent calcium current by extracellular ATP in
      hamster ventricular cardiomyocytes.
AB  - The modulation of the high-voltage-activated calcium current (ICa) by external
      ATP was examined in single ventricular cardiomyocytes of the hamster using the
      whole-cell configuration of the patch-clamp technique. Extracellular application
      of ATP (0.1-100 microM) was found to inhibit ICa reversibly. The inhibition
      followed a slow time course (half time approximately 25 s) and was accompanied by
      very small changes of the holding current and no shift in the current-voltage
      relationship. With 100 microM ATP, peak ICa was reduced by approximately 30%.
      This response was not blocked by the P1 inhibitor 8-cyclopentyl-1,3
      dipropylxanthine. The nonhydrolyzable ATP analogs adenosine 5'-O-(3
      thiotriphosphate) and AMP-adenosine 5'-[beta,gamma-imido]triphosphate also
      reduced ICa. The ATP analog alpha,beta-methylene-ATP was about equipotent with
      ATP at 50 microM. Internal guanosine 5'-O-(3-thiotriphosphate) (200 microM)
      rendered the ATP-mediated inhibition of ICa poorly reversible, whereas internal
      guanosine 5'-O-(2-thiodiphosphate) (200-500 microM) had no effect. Holding the
      intracellular adenosine 3',5'-cyclic monophosphate concentration at a constant
      high level did not alter the ATP response. We conclude that external ATP inhibits
      ICa via a P2 purinergic receptor in hamster ventricular myocytes. Our results
      suggest the involvement of a G protein not coupled to adenylate cyclase. The
      inhibition of ICa by extracellular ATP might have pathophysiological relevance
      under conditions of myocardial injury.

PMID- 9249499
TI  - Altered vascular function after adenovirus-mediated overexpression of endothelial
      nitric oxide synthase.
AB  - Gene transfer with replication-deficient adenovirus is a potentially useful tool
      to study vascular biology. We have constructed a replication-deficient adenovirus
      (AdRSVeNOS) that carries cDNA for endothelial nitric oxide synthase (eNOS).
      Transfection of COS-1 cells with AdRSVeNOS increased nitric oxide synthase
      activity (measured as production of L-citrulline from L-arginine) that was
      calcium dependent and inhibited by N omega-nitro-L-arginine methyl ester. To
      investigate effects of overexpression of eNOS on vascular function, we incubated
      common carotid arteries from rabbits in organ culture with AdRSVeNOS or AdRSV
      beta gal encoding beta-galactosidase. Transgene expression and responses to
      vasoactive agents were examined 1 day after transduction. Histochemical staining
      of beta-galactosidase and immunohistochemistry for eNOS indicated transgene
      expression in endothelium and adventitial cells. After precontraction with
      phenylephrine, vessels treated with AdRSVeNOS demonstrated greater relaxation to
      acetylcholine than vessels treated with vehicle or AdRSV beta gal. Relaxation to
      calcium ionophore A-23187 was much greater in vessels treated with AdRSVeNOS than
      in vessels treated with vehicle or AdRSV beta gal. Augmented relaxation in
      response to A-23187 was also observed after denudation of endothelium in vessels
      treated with AdRSVeNOS and was inhibited by N omega-nitro-L-arginine. Thus
      vasorelaxation in response to stimuli that release nitric oxide is augmented
      after adenovirus-mediated overexpression of eNOS. Transgene expression in
      adventitial cells appears to be sufficient to alter vasomotor function.

PMID- 9249498
TI  - Myogenic constriction of human coronary arterioles.
AB  - Myogenic constriction is an important mechanism of blood flow regulation;
      however, it has never been demonstrated in the human coronary circulation. We
      examined responses of human coronary resistance vessels in vitro to changes in
      intraluminal pressure and evaluated the role of protein kinase C (PKC).
      Microvessels (passive diameter 44-227 microns) were dissected from atrial
      appendages obtained during cardiac surgery and studied under conditions of zero
      flow. In response to stepped increases in pressure, there was a graded response
      such that at 100 mmHg, vessels constricted to 55 +/- 4% of their passive
      diameter. There was an inverse relationship between vessel diameter and myogenic
      responsiveness. Basal tone was attenuated by inhibition of voltage-dependent
      calcium channels (VDCC) with diltiazem and by inhibition of PKC with calphostin
      C. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) enhanced basal
      tone. Active myogenic constriction was also impaired by calphostin C and
      augmented by PMA. Arterioles from patients with hypertension demonstrated
      enhanced myogenic constriction compared with vessels from normotensive patients
      (0.55 +/- 0.04 vs. 0.74 +/- 0.03; P < 0.01). These results demonstrate myogenic
      constriction in the human coronary microcirculation. Regulation of extracellular
      calcium by VDCC and intracellular calcium by PKC are important in mediating the
      magnitude of basal tone and myogenic responsiveness of these vessels.

PMID- 9249500
TI  - Mechanical workload-myocardial water content relationship in isolated rat hearts.
AB  - We tested the hypothesis that the mechanical workload of the heart inversely
      determines the rate of myocardial edema formation in an isolated, perfused rat
      heart preparation. Heart rate (HR) was varied in three groups by pacing at 125
      (HR125), 250 (HR250), or 350 beats/min (HR350). Left ventricular pressure (LVP)
      was varied in two additional groups by pacing at 250 beats/min and with the
      addition of either epinephrine (Epi) or propranolol (Pro) to the perfusate. In
      five otherwise identical groups, variation of coronary vascular resistance was
      minimized by adenosine. Myocardial water content (MWC) varied significantly and
      inversely with HR in the HR125, HR250, and HR350 groups. MWC of the HR250 group
      was significantly less than that of the Pro group but did not differ from the Epi
      group. However, when adenosine was used, MWC had significant inverse
      relationships with HR and LVP. We concluded that the mechanical workload of the
      heart inversely determines the rate and degree of myocardial edema formation in
      this isolated heart preparation, and both HR and LVP are determinants of this
      relationship.

PMID- 9249501
TI  - Desensitization of norepinephrine receptor function is associated with G protein
      uncoupling in the rat aorta.
AB  - Infusion of norepinephrine (NE) in rats results in desensitization of NE-mediated
      aortic contraction and a reduction (55% at 1 and 10 microM) in NE-stimulated
      vascular inositol phosphate accumulations. The functional responses to
      angiotensin II (ANG II) were also reduced in the tissues of NE-infused animals.
      alpha 1-Adrenoceptor number determined by 2-[beta-(4-hydroxy-3-[125I]iodophenyl)
      ethylaminomethyl]-tetralone ([125I]HEAT) binding and levels of G alpha or G beta
      proteins measured by immunoblot analyses were not changed in the aortic membranes
      of NE-infused animals. To determine whether desensitization is associated with
      receptor-G protein uncoupling, agonist-stimulated palmitoylation of G alpha
      proteins was measured. NE infusion decreased phenylephrine (1 microM)-stimulated
      [3H]palmitate incorporation into Gq alpha, Gs alpha, and Gi alpha proteins and
      ANG II (10 microM)-stimulated palmitoylation of Gq alpha and Gi alpha in aortic
      membranes. Phenylephrine- and ANG II-stimulated guanosine 5'-O-(3
      [35S]thiotriphosphate) binding to Gq alpha was also decreased in the aortas of NE
      infused animals. These results show that an infusion of NE causes heterologous
      desensitization of the contractile and inositol phosphate accumulation responses
      in the rat aorta and that these changes are mediated by an uncoupling of
      receptors from their G proteins.

PMID- 9249502
TI  - Cytoskeletal rearrangement mediates human microvascular endothelial tight
      junction modulation by cytokines.
AB  - The tight junction (TJ) is a specialized intercellular structure responsible for
      the regulation of ionic and macromolecular flux across cell monolayers. Because
      plasma leakage is believed to occur mainly across the microvasculature, we
      hypothesized that microvascular endothelial cells (MVEC) may form more intact,
      regulatable TJ than other endothelial cell (EC) types, allowing further insight
      into the control of EC permeability. Primary cultures of MVEC monolayers produced
      transmonolayer electrical resistances (TER) of 120-155 omega.cm2, approximately
      10 times that of large-vessel EC. Treatment with tumor necrosis factor and
      interferon-gamma caused a 50% decrease in the TER and a striking fragmentation of
      the basal, continuous interendothelial cell zonula occludens-1 protein (ZO-1)
      distribution determined by immunofluorescence. Fragmentation was inhibited by
      cytochalasin D, and confocal microscopy demonstrated a colocalization between F
      actin and ZO-1. These findings suggest that the F actin cytoskeleton plays a
      central role in endothelial TJ barrier regulation and that dynamic cytoskeletal
      alterations may primarily control vascular permeability.

PMID- 9249503
TI  - Left ventricular parallel conductance during cardiac cycle in children with
      congenital heart disease.
AB  - This study examines the accuracy of the conductance catheter technique and, in
      particular, parallel conductance [expressed as offset volume (Vc)] changes during
      the cardiac cycle in the human left ventricle. Two groups of patients were
      assessed: group 1, with an open atrial septal defect, and group 2, with an
      interventricular communication. In a subgroup, pre- and postoperative data were
      compared to assess the possible impact of shunting or anatomic considerations on
      our measurements. Vc is normally obtained by a saline-dilution technique
      previously described by Baan et al. [Vc(Baan); J. Baan, E. T. Van der velde, H.
      G. Debruin, G. J. Smeenk, J. Koops, A. D. Van Dijk, D. Temmerman, P. J. Senden,
      and B. Buis. Circulation 70: 812-823, 1984]. This does not take into account
      potential changes during the cardiac cycle. Four cardiac cycles were taken from
      the hypertonic saline washin and were divided into six equal isochrones between
      the maximum and minimum first derivatives of left ventricular pressure (dP/dtmax
      and dP/dtmin, respectively). The apparent ventricular volume was regressed
      against stroke volume for the corresponding cardiac cycle. The volume at the
      gamma-intercept corresponds to the Vc at each time interval [Vc(t)]. In group 1,
      there was a variation in Vc(t) during systole, but the temporal changes were
      quite small, on the order of 4.28% (SD = 5.18%) of total corrected end-diastolic
      volume (mean maximal variation of 2.60 ml). Furthermore, the value of Vc obtained
      at dP/dtmax was not significantly different from that obtained at dP/dtmin. For
      group 2 as a whole, mean Vc(Baan) did not change significantly with ventricular
      septal defect closure (preoperative, 8.85 +/- 11.1 ml; postoperative, 9.82 +/-
      11.84 ml). Group 2 children also exhibited a systolic cyclical variation in Vc(t)
      similar to group 1. Finally, Vc(t) as a percentage of end-diastolic volume was no
      different when group 1 and group 2 were compared. We conclude that in the left
      ventricle, even in the presence of a left-to-right shunt, there is a small but
      insignificant difference in parallel conductance during ventricular ejection. The
      magnitude of this cyclical change does not preclude ventricular volume
      measurement in congenital heart disease by the conductance catheter technique.

PMID- 9249504
TI  - Skeletal muscle ischemia-reperfusion causes transitory increase in microvascular
      protein permeability.
AB  - The aim of this study was to determine whether the length of ischemia in skeletal
      muscle influences the return of normal microvascular permeability during
      reperfusion in addition to influencing the size of the initial changes. In
      anesthetized rabbits, the transvascular clearance of labeled albumin was measured
      in the gastrocnemius and soleus muscles during the first, second, third, or
      fourth hour of reperfusion after 1, 2, 3, or 4 h of ischemia. The size of the
      increases in albumin clearance, tissue water, and myeloperoxidase activity during
      the first hour of reperfusion was dependent on the length of ischemia. The return
      of the albumin clearance to control values during the fourth hour of reperfusion
      was independent of the length of ischemia. Tissue water, extravascular mass of
      native albumin, and myeloperoxidase activity remained elevated during the 4 h of
      reperfusion. After 4 h of ischemia, the solvent-drag reflection coefficient for
      albumin was significantly less than control during the first hour of reperfusion.
      The value during the fourth hour of reperfusion was not significantly different
      from control. These results suggest that the inflammatory mediators producing a
      change in permeability are washed out of the microvasculature during the first
      few hours of reperfusion.

PMID- 9249505
TI  - Cumulative conducted vasodilation within a single arteriole and the maximum
      conducted response.
AB  - The vascular network functions to distribute blood flow to the tissues that
      require it, and conducted vasodilation may facilitate this function. Experiments
      on arterioles in anesthetized hamster cheek pouch modeled the conducted responses
      that may come from a series of neighboring capillary modules and determined
      whether cumulative conducted responses could thereby maximally dilate upstream
      arterioles. Methacholine (10(-5) M) was simultaneously microapplied on an
      arteriole (resting diameter, approximately 22 microns; maximum diameter,
      approximately 47 microns) from one to four micropipettes spaced 100 microns
      apart, and with each added pipette the conducted dilation increased (up to a
      maximum dilation of approximately 5 microns). Increasing the methacholine 10-fold
      (10(-4) M) did not further increase the conducted response. The conducted
      response could also not be increased by lengthening the duration of
      microapplication. Yet, dilations that were not cumulative along a single
      arteriole became cumulative when initiated instead on adjacent arterioles.
      Therefore, these data demonstrate that conducted dilation along a single
      arteriole is limited and, if this model is correct, suggest that neighboring
      capillary modules may communicate only a limited conducted response to the
      network.

PMID- 9249506
TI  - cAMP induces heme oxygenase-1 gene expression and carbon monoxide production in
      vascular smooth muscle.
AB  - Recent studies indicate that vascular smooth muscle cells generate carbon
      monoxide (CO) via the action of heme oxygenase (HO). Because adenosine 3',5'
      cyclic monophosphate (cAMP) is an important intracellular signaling molecule in
      the regulation of vascular cell function, we examined whether this second
      messenger modulates the expression of HO and the production of CO by rat aortic
      smooth muscle cells. Treatment of smooth muscle cells with the membrane-permeable
      cAMP derivative dibutyryl cAMP or with compounds that increase intracellular cAMP
      levels (isoproterenol and forskolin) resulted in a concentration- and time
      dependent increase in the levels of HO-1 mRNA and protein, whereas the expression
      of HO-2 remained unchanged. Both actinomycin D and cycloheximide blocked the
      basal expression of HO-1 mRNA and protein and prevented the cAMP-mediated
      induction of HO-1. Incubation of platelets with cAMP-treated smooth muscle cells
      resulted in a significant increase in platelet cGMP concentration that was
      partially reversed by treatment of smooth muscle cells with the nitric oxide
      synthase inhibitor NG-monomethyl-L-arginine or the HO blocker zinc protoporphyrin
      IX. However, the combined addition of these two inhibitors to cAMP-treated smooth
      muscle cells or the addition of the CO and NO scavenger hemoglobin to platelets
      completely blocked the stimulatory effect on platelet cGMP levels. These results
      demonstrate that cAMP induces the expression of the HO-1 gene and stimulates the
      formation of CO and NO in vascular smooth muscle cells. The capacity of cAMP to
      induce the synthesis of guanylate cyclase-stimulatory CO from smooth muscle cells
      may represent a novel mechanism by which this nucleotide regulates vascular tone.

PMID- 9249507
TI  - Effects of sevoflurane on inward rectifier K+ current in guinea pig ventricular
      cardiomyocytes.
AB  - The effects of sevoflurane on the inward rectifier potassium current (IKIR) were
      examined in guinea pig ventricular cardiomyocytes using the whole cell patch
      clamp methodology. Sevoflurane had a unique dual effect on the steady-state
      current amplitude, producing a reversible, concentration- and voltage-dependent
      block of the inward current at potentials negative to the potassium equilibrium
      potential (EK) but enhancing the outward current positive to EK. Accordingly, the
      steady-state conductance negative to EK was reduced by sevoflurane, but
      conductance positive to EK was increased. The chord conductance-voltage
      relationship showed depolarizing shifts at 0.7, 1.3, and 1.6 mM sevoflurane. When
      the myocytes were dialyzed with 10 mM Mg2+, but not with 1.0 mM Mg2+, sevoflurane
      further slowed current activation kinetics. With 10 mM intracellular Mg2+, the
      outward current enhancement by sevoflurane and the associated shifts in half
      activation potential were abolished. Polyamines abolished all effects of
      sevoflurane on IKIR. With the use of the Woodhull model for voltage-dependent
      block, we determined the sevoflurane interaction site with the inward rectifier
      potassium channel to be at an electrical distance of 0.2 from the extracellular
      side.

PMID- 9249508
TI  - Newborn piglet cerebral microvascular responses to epoxyeicosatrienoic acids.
AB  - The present study on the newborn pig cerebral microcirculation determined the
      vasoactive properties of epoxyeicosatrienoic acids (EETs) and the contributions
      of prostaglandin cyclooxygenase to these properties. Pial arterioles of
      anesthetized piglets were observed through closed cranial windows, EETs were
      applied topically, and artificial cerebrospinal fluid from beneath the cranial
      windows was collected for the determination of adenosine 3',5'-cyclic
      monophosphate and 6-ketoprostaglandin F1 alpha. EETs caused dilation of pial
      arterioles and increased adenosine 3',5'-cyclic monophosphate. 5,6-EET produced a
      dose-dependent dilation at 10(-8) M and above, whereas 10(-6) M was required for
      8,9-EET, 11,12-EET, and 14,15-EET. Indomethacin abolished pial arteriolar
      dilation to the EETs. However, EETs did not increase cortical 6-ketoprostaglandin
      F1 alpha concentration. Treatment of indomethacin-treated piglets with iloprost
      (10(-12) M topically) restored dilation to 5,6-EET. Neither isoproterenol nor
      sodium nitroprusside allowed vasodilation to 5,6-EET in indomethacin-treated
      piglets. Therefore, in the newborn pig cerebral microvasculature. EETs are potent
      vasodilators and prostacyclin-receptor agonists are necessary to allow this
      dilation to occur.

PMID- 9249509
TI  - Systemic and renal hemodynamic effects of hemorrhage in conscious lambs.
AB  - The purpose of the present study was to investigate the systemic and renal
      hemodynamic effects of hemorrhage in the newborn to determine whether the newborn
      is capable of restoring blood pressure in the face of blood loss at hemorrhage of
      up to 20% of vascular volume. Experiments were carried out in conscious,
      chronically instrumented lambs and consisted of measurements before, during, and
      after hemorrhage at 0 (n = 9), 10 (n = 8), 15 (n = 8), and 20% (n = 8) of blood
      volume. Right atrial pressure decreased but only after 20% hemorrhage. There was
      a transient decrease in blood pressure at 10-15% hemorrhage and a sustained
      decrease in blood pressure after 20% hemorrhage (from 82 +/- 7 to 66 +/- 9 mmHg).
      Heart rate increased transiently after 15% hemorrhage (from 173 +/- 32 to 204 +/-
      66 beats/min); heart rate remained increased for 60 min after 20% hemorrhage from
      171 +/- 17 to 214 +/- 31 beats/min. There were no changes in renal vascular
      resistance in response to hemorrhage of up to 20% of vascular volume. These
      observations provide evidence that the newborn is capable of buffering blood
      pressure in response to blood loss of up to 20% of vascular volume and that the
      renal bed does not appear to contribute to the restoration of blood pressure
      after blood loss early in life.

PMID- 9249511
TI  - Meandering and unstable reentrant wave fronts induced by acetylcholine in
      isolated canine right atrium.
AB  - The mechanism(s) by which acetylcholine (ACh) increases atrial vulnerability to
      reentry and maintains its activity for longer durations remains poorly defined.
      In the present study we used high-resolution activation maps to test the
      hypothesis that ACh promotes meandering of atrial reentrant wave fronts,
      resulting in breakup and the generation of new wave fronts that sustain the
      activity. Reentry was induced in 11 isolated canine right atrial tissues (3.8 x
      3.2 cm) by a premature point stimulus (S2) before and after superfusion with ACh
      (15 x 10(-6) M). Endocardial isochronal activation maps were constructed with the
      use of 509 bipolar electrodes (1.6-mm spatial resolution), and the dynamics of
      the activation wave fronts were visualized with animation. A vulnerable period
      was found during which an S2 current strength > 4.4 +/- 2.5 mA [lower limit of
      vulnerability (LLV)] and < 26 +/- 13 mA [upper limit of vulnerability (ULV)]
      induced a single stationary reentrant wave front that lasted 3 +/- 2.5 s with a
      period of 159 +/- 17 ms (16 episodes). AC shortened the refractory period from
      100 +/- 12 to 59 +/- 9 ms (P < 0.001) and increased vulnerability to reentry
      induction by simultaneous decrease in the LLV (0.7 +/- 0.2 mA, P < 0.001) and an
      increase in the ULV (82 +/- 24 mA, P < 0.01). ACh accelerated the rate (period of
      110 +/- 16 ms, P < 0.001) and converted the stationary reentrant wave front to a
      nonstationary (meandering) reentrant wave front showing polymorphic electrograms,
      i.e., "fibrillation-like" activity (22 episodes). Rapid meandering of the reentry
      tip led to wave front breakup (18 episodes) and the generation of new wave fronts
      (19 episodes). These wave front dynamics also led to sustained (76 +/- 224 s, P <
      0.001) fibrillation-like electrograms. We conclude that ACh increases the ULV and
      promotes meandering of a single reentrant wave front, leading to breakup and the
      generation of new wave fronts. Single meandering and complex wave front dynamics
      cause fibrillation-like activity and sustain the activity for longer duration.

PMID- 9249512
TI  - Diabetic human platelets release a substance that inhibits platelet-mediated
      vasodilation.
AB  - This study was performed to investigate the mechanism for impaired vasodilation
      in response to activated diabetic human platelets. As observed previously,
      diabetic platelets failed to cause vasorelaxation, whereas normal platelets
      produced normal vasodilation. However, when activated and perfused through
      quiescent, NG-nitro-L-arginine-pretreated arteries, diabetic and normal platelets
      caused similar degrees of vasoconstriction. Inhibition of serotonergic and
      thromboxane A2 receptors in preconstricted normal arteries also failed to improve
      vasodilatory responses to diabetic platelets. The amount of ADP released into the
      supernatant from activated diabetic and normal platelets was similar. Concomitant
      perfusion of activated diabetic platelets impaired vasodilation produced by
      abluminally applied acetylcholine but perfusion of normal platelets did not.
      Whereas activated diabetic platelets failed to produce vasodilation, supernatant
      from the same platelets caused normal vasorelaxation. Dimethylthiourea and Tiron,
      intracellular free radical scavengers, normalized the vasodilatory response to
      diabetic platelets, whereas superoxide dismutase, catalase, and mannitol did not.
      We conclude that the impaired vasorelaxation in response to activated diabetic
      platelets is caused by an unidentified, short-acting, platelet-derived
      substance(s) that interferes with the normal dilatory response.

PMID- 9249513
TI  - Role of leukocytes in cerebral autoregulation and hyperemia in bacterial
      meningitis in rabbits.
AB  - The effect of leukocytes on regional cerebral blood flow (rCBF) and
      cerebrovascular autoregulation in experimental meningitis was determined in
      rabbits. Four groups of animals were studied. Cerebrospinal fluid (CSF) leukocyte
      migration was prevented in two groups by pretreatment with 1.5 mg/kg of IB4, a
      monoclonal antibody directed against CD11/18 leukocyte adhesion receptors.
      Intracisternal inoculation was performed with saline (control and control-IB4
      groups) or Haemophilus influenzae type b (Hib and Hib-IB4 groups). Eighteen hours
      later, rCBF was determined with radiolabeled microspheres. Autoregulation was
      assessed by graded hemorrhagic hypotension. Compared with untreated meningitis
      (Hib group), IB4-pretreated meningitis (Hib-IB4 group) was associated with a
      reduced CSF leukocyte count (1,980 +/- 880 vs. 200 +/- 110 cells/microliter; P <
      0.05) and an elevated CSF colony count (2.87 +/- 0.08 vs. 5.63 +/- 0.72
      log10colony-forming units/ml; P < 0.05). Compared with control, baseline CBF was
      elevated in both untreated and IB4-pretreated meningitis (51 +/- 2, 54 +/- 2, 66
      +/- 5, and 102 +/- 17 ml.100 g-1.min-1 in control, control-IB4, Hib, and Hib-IB4
      groups, respectively). The degree of hyperemia in meningitis was related to the
      CSF colony count, with a high CBF occurring in animals with high colony counts.
      During hypotension, CBF remained at or above baseline in the Hib group and both
      control groups, indicating preservation of cerebrovascular autoregulation in
      untreated Hib meningitis. In the Hib-IB4 group, the elevated baseline CBF was not
      maintained during hypotension, falling to 51% of baseline at a cerebral perfusion
      pressure of 30 mmHg and indicating impairment of cerebrovascular autoregulation.
      These results suggest that CSF leukocytes are not primarily responsible for the
      hyperemic response in Hib meningitis. Cerebral hyperemia may be induced either
      directly by bacterial components or indirectly by components of the inflammatory
      cascade that precede CSF leukocyte migration.

PMID- 9249514
TI  - Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in
      mice.
AB  - This study identified the organ and cellular distribution of cationic liposome
      DNA complexes injected intravenously into CD-1 mice for gene delivery. DOTIM
      cholesterol liposomes were labeled with the fluorescent dye CM-Dil and complexed
      with plasmid DNA encoding the chloramphenicol acetyltransferase reporter gene.
      The distribution of the complexes was examined in 29 organs and tissues by
      fluorescence, confocal, and electron microscopy from 5 min to 24 h after
      injection. The complexes formed clusters in blood, which were cleared within 20
      min. Complexes visible by fluorescence microscopy were taken up by endothelial
      cells, leukocytes, and macrophages and did not leave the vasculature except in
      the spleen. At 5 min, the complexes formed a patchy coating on the endothelial
      surface, but by 4 h, they were internalized into endosomes and lysosomes in organ
      and vessel-specific patterns. Uptake by capillary endothelial cells was greatest
      in the lung, ovary, and anterior pituitary, less in muscle and the heart, and
      nearly absent in the brain and pancreatic islets. In lymph nodes and intestinal
      Peyer's patches, the uptake was sparse in capillaries but abundant in high
      endothelial venules. In the liver and spleen, most of the uptake was in Kupffer
      cells and macrophages. Measurements of chloramphenicol acetyltransferase reporter
      gene expression were generally consistent with the pattern of uptake by
      endothelial cells. The uptake and gene expression were accompanied by a decrease
      in circulating leukocytes and platelets. Overall, our results showed that the
      complexes were internalized by endothelial cells in organ- and vessel-specific
      patterns that did not match any previously identified properties of the
      microvasculature. The unusual distribution of endothelial cell uptake may be
      explained by a heterogeneously distributed membrane receptor for which the
      complexes are ligands.

PMID- 9249510
TI  - Role of cytoskeleton in shear stress-induced endothelial nitric oxide production.
AB  - To study the role of the cytoskeleton in mechanochemical transduction, human
      umbilical vein endothelial cells were exposed to cytoskeleton-disrupting or 
      stabilizing agents, and the flow-induced production of nitric oxide (NO) as
      monitored by intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP)
      was examined. A shear stress of 20 dyn/cm2 elevated cGMP levels approximately
      twofold relative to basal (stationary) levels (1.9 +/- 0.1 pmol cGMP in
      stationary controls; P < 0.01). Treatment with 1 microM phalloidin and 0.5 microM
      cytochalasin D did not significantly affect the flow-induced response (1.77 +/-
      0.23 and 2.89 +/- 0.18 pmol cGMP in stationary controls, respectively), whereas
      disruption of microtubules with 0.5 microM colchicine significantly elevated the
      response (3.64 +/- 0.18 pmol cGMP in stationary controls; P < 0.01). The NO
      synthase inhibitor NG-amino-L-arginine abrogated all flow-induced elevations of
      cGMP, indicating that increased cGMP levels were mediated by NO. Cytoskeletal
      disruption with 0.2 microM cytochalasin D or 0.5 microM colchicine did not alter
      cGMP levels in response to 10 nM bradykinin. The role of the plasma membrane in
      mechanochemical transduction was examined by treatment with cholesteryl
      hemisuccinate, which attenuated the flow-induced response in a dose-dependent
      manner. In conclusion, the pathways of flow- and bradykinin-mediated NO
      production in endothelial cells did not require actin filament turnover or intact
      actin or microtubule cytoskeletons, and cholesterol, possibly by stiffening the
      plasma membrane, attenuated the flow response.

PMID- 9249515
TI  - Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic
      exercise in humans.
AB  - The role of nitric oxide at rest and in the active hyperemic response within
      skeletal muscle was investigated in eight physically active men. Three
      microdialysis probes were inserted into the vastus lateralis of the quadriceps
      femoris muscle group in each subject. Microdialysis probes were perfused with a
      Ringer solution containing 5.0 mM ethanol, 2.5 mM glucose, and either 10 mg/ml of
      the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) monoacetate
      salt, 30 mg/ml of the nitric oxide precursor L-arginine, or no additional
      substance (control probe). Subjects performed one-legged cycling exercise at work
      rates ranging from 25 to 100 W. Dialysate and perfusate ethanol concentrations
      were presented as the ratio of [ethanol]dialysate to [ethanol]perfusate (ethanol
      outflow-to-inflow ratio), an indicator that is inversely related to blood flow.
      The ethanol outflow-to-inflow ratios at rest were 0.614 +/- 0.032, 0.523 +/-
      0.023, and 0.578 +/- 0.039 in the L-NMMA, L-arginine, and control probes,
      respectively. Calculated resting blood flows were therefore 8.7 +/- 4.1, 20.5 +/-
      4.6, and 14.0 +/- 4.7 ml.min-1.100 g-1 around the L-NMMA, L-arginine, and control
      probes, respectively. The ethanol outflow-to-inflow ratios were significantly
      higher at all exercise intensities in the L-NMMA probe than in the control and L
      arginine probes, resulting in calculated blood flows of 195 +/- 55, 407 +/- 47,
      and 352 +/- 60 ml.min-1.100 g-1 at 25 W and 268 +/- 65, 602 +/- 129, and 519 +/-
      113 ml.min-1.100 g-1 at 100 W around the L-NMMA, L-arginine, and control probes,
      respectively. Skeletal muscle blood flow was therefore reduced both at rest and
      during continuous, dynamic exercise by the action of L-NMMA, whereas blood flow
      was increased only at rest by L-arginine.

PMID- 9249516
TI  - Atrial natriuretic peptide expression in rats with different pulmonary
      hypertensive responses to hypoxia.
AB  - Mechanisms that regulate atrial natriuretic peptide (ANP) expression during
      hypoxia are not well defined. We hypothesized that plasma immunoreactive ANP
      (irANP) and right heart irANP and ANP mRNA levels would be greater in a strain of
      Sprague-Dawley rats that develops more severe hypoxic pulmonary hypertension (H
      rats) than another strain (M rats). After 3 wk of hypoxia (0.5 atm), right
      ventricular systolic pressure (RVSP) and the right ventricle (RV) weight-to-left
      ventricle plus septum (LV (+) S) weight ratio [RV/(LV+S)] were greater in H rats
      than in M rats (70 +/- 4 vs. 40 +/- 2 mmHg and 0.59 +/- 0.02 vs. 0.50 +/- 0.02,
      respectively; P < 0.05 for both), but plasma ANP increased twofold and RV irANP
      and ANP mRNA increased fivefold in both rat strains. After 3 days of normoxic
      recovery from chronic hypoxia, RVSP, RV/(LV+S), and RV irANP and ANP mRNA levels
      decreased in M rats but not in H rats. Plasma irANP decreased to baseline levels
      in both rat strains. We conclude that, in addition to changes in RV pressure and
      hypertrophy, hypoxia acts through other mechanisms to modulate RV ANP synthesis
      and circulating ANP levels in hypoxia-adapted rats.

PMID- 9249517
TI  - Amelioration of ischemic calcium overload correlates with high-energy phosphates
      in senescent myocardium.
AB  - Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each)
      cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was
      associated with enhanced functional recovery after surgically induced global
      ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic
      cytochrome oxidase I activity and mRNA levels, suggesting that enhanced
      functional recovery may involve the preservation of high-energy phosphates. To
      investigate this hypothesis, 31P nuclear magnetic resonance was used to measure
      serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside
      triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH
      (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia,
      global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded
      PCr depletion (P < 0.05) and significantly enhanced NTP preservation (P < 0.05)
      during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase
      in Mgf during ischemia (P < 0.05). These results were correlated with
      amelioration of [Ca2+]i accumulation during ischemia and preservation of left
      ventricular function after reperfusion and suggest that optimal functional
      recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the
      aged myocardium.

PMID- 9249518
TI  - Endothelium-derived nitric oxide limits sympathetic neurogenic constriction in
      intestinal microcirculation.
AB  - We have recently shown that endogenous nitric oxide (NO) activity can attenuate
      the sympathetic neurogenic constriction of intestinal arterioles. The purpose of
      this study was to determine whether the microvascular endothelium is an important
      site of NO production under these conditions. In the superfused small intestine
      of the rat, intravital microscopy was used to study the responses of first-order
      arterioles (1A) to perivascular sympathetic nerve stimulation and directly
      applied norepinephrine before and then after passage of a CO2 embolus through the
      1A lumen to inhibit endothelial function. CO2 embolization did not significantly
      alter resting arteriolar diameter (50 +/- 4 microns before vs. 51 +/- 4 microns
      after embolization) but abolished the dilator response to acetylcholine without
      altering the dilator response to sodium nitroprusside. Stimulation at 3, 8, and
      16 Hz caused respective constrictions of 4 +/- 1, 11 +/- 1, and 18 +/- 2 microns,
      and after CO2 these responses were significantly increased to 9 +/- 1, 18 +/- 1,
      and 29 +/- 3 microns, respectively. Exposure to the nitric oxide synthase
      inhibitor NG-monomethyl-L-arginine(10(-4) M in superfusate) after CO2
      embolization had no further effect on the magnitude of neurogenic constriction.
      Similar results were seen when embolization was achieved with N2, and CO2
      embolization had the same effect on norepinephrine-induced constriction as it did
      on neurogenic constriction. These results suggest that nitric oxide of
      endothelial origin can attenuate sympathetic neurogenic constriction in the
      intestinal microvasculature.

PMID- 9249519
TI  - Motor responses of cultured rat cerebral vascular smooth muscle cells to intra-
      and extracellular pH changes.
AB  - Alkalizing perivascular fluid constricts, whereas acidification dilates, cerebral
      arterioles. It is not known whether vascular smooth muscle cells (VSMCs),
      endothelium, or neuronal elements sense pH changes. We hypothesized that VSMCs
      themselves transduce extracellular pH (pHo) changes. We examined the motor
      responses of cultured adult rat middle cerebral arterial VSMCs during pHo and
      intracellular pH (pHi) changes. Motor responses were inferred from the
      deformation pattern of a silicone substratum, dimethylpolysiloxane, which
      wrinkles as cells contract. pHi was measured with 2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein. Cultured VSMCs retained motor responses to vasoconstrictors
      (5-hydroxytryptamine and K+), and to sodium nitroprusside, which were typical of
      intact arterioles. VSMCs contracted with increasing and relaxed with decreasing
      pHo. Hypocapnia contracted VSMCs when the pHo increased, and hypercapnia relaxed
      VSMCs when the pHo decreased. However, at a constant pHo, changes in PCO2 caused
      opposite responses despite equivalent changes in pHi. Thus VSMCs contract with
      increased pHo and relax with decreased pHo just as intact arterioles do. These
      responses do not reflect changes in pHi or PCO2. pHi changes paradoxically alter
      VSMC tone in the direction opposite that caused by pHo changes.

PMID- 9249520
TI  - Contributions of the specialized conduction system to the activation sequence in
      the canine pulmonary conus.
AB  - This study was designed to characterize the relative contributions of the
      specialized conduction system and the myocardial architecture to the ventricular
      activation sequence. In animal experiments, the activation sequence within a 14 x
      14-mm region on each surface of the pulmonary conus from isolated canine hearts
      was determined from electrograms recorded during ventricular drives applied at
      the periphery of the measurement region. Recordings were obtained simultaneously
      from electrode arrays mounted on the endocardium and epicardium. Activation
      sequences were determined before and after the right ventricular cavity was
      bathed with a dilute Lugol-normal Tyrode (LNT) solution that selectively
      inhibited excitation of Purkinje cells. Simulations of action potential
      propagation in three-dimensional models (14.4 mm long x 7.2 mm wide x 3.6 mm
      thick) that included the major features of the midwall architecture were
      performed to aid in the interpretation of the experimental findings. During
      endocardial pacing (7 animals, 43 total drives), LNT application markedly
      prolonged the endocardial (13.7 +/- 1.3 ms) and epicardial (5.7 +/- 1.0 ms)
      activation sequences. However, epicardial isochrone maps constructed with
      electrograms recorded before LNT application showed no signs of multiple
      breakthrough sites and, with the exception of overall timing, closely resembled
      isochrone maps constructed with electrograms recorded after LNT application.
      During epicardial pacing (9 animals, 55 total drives), LNT application prolonged
      the endocardial (3.7 +/- 0.6 ms) and epicardial (1.9 +/- 0.6 ms) activation
      sequences much less dramatically than during endocardial pacing, suggesting a
      primary contribution of myocardial architecture. However, in those instances
      where nonuniform anisotropy slowed epicardial expansion of the depolarization
      wavefront, the specialized conduction system contributed to the activation
      sequence to a greater extent.

PMID- 9249521
TI  - Numerical simulation of mass transfer in porous media of blood vessel walls.
AB  - The tunica media of a blood vessel wall is modeled as a heterogeneous medium
      composed of a periodic array of cylindrical smooth muscle cells and a continuous
      interstitial fluid phase of proteoglycan and collagen fibers. By applying
      Brinkman's model to describe the behavior of the interstitial flow, we obtain an
      analytical solution for the transmural flow field through the periodic array of
      smooth muscle cells in the form of a power series, making it possible to compute
      the convection of solutes in the interstitial phase. With reaction of solutes at
      the surface of smooth muscle cell membranes being treated as boundary conditions
      and the diffusion of species being limited to the interstitial fluid phase only,
      mass transfer in the media of blood vessel walls is simulated numerically using
      Cray supercomputers. It is found that the Sherwood number (the dimensionless mass
      transfer coefficient) is not only constant for all interior smooth muscle cells
      but also minimally sensitive to changes of parameters controlling the relative
      rates of diffusion and convection in the interstitial fluid phase and the
      reaction on the smooth muscle cell surface. In addition, the Sherwood number is
      not very sensitive to changes in the volume fraction of smooth muscle cells. A
      homogeneous, one-dimensional model (effective-medium model) is also developed to
      predict the bulk concentration profile in the media, based on the equivalent
      properties of the effective medium derived from the heterogeneous medium. A
      comparison of results from the one-dimensional model and two-dimensional
      simulation is quite satisfactory for all practical ranges of parameters. It is
      also determined that, for a small molecule such as ATP, the mass transfer to the
      surface of smooth muscle cells is "reaction limited" as assumed previously in the
      literature, whereas, for a large molecule such as low-density lipoprotein, the
      mass transfer might not be reaction limited.

PMID- 9249522
TI  - Low power, type II errors, and other statistical problems in recent
      cardiovascular research.
AB  - Frequently in biomedical literature, measurements are considered "not
      statistically different" if a statistical test fails to achieve a P value that is
      < or = 0.05. This conclusion may be misleading because the size of each group is
      too small or the variability is large, and a type II error (false negative) is
      committed. In this study, we examined the probabilities of detecting a real
      difference (power) and type II errors in unpaired t-tests in Volumes 246 and 266
      of the American Journal of Physiology: Heart and Circulatory Physiology. In
      addition, we examined all articles for other statistical errors. The median power
      of the t-tests was similar in these volumes (approximately 0.55 and approximately
      0.92 to detect a 20% and a 50% change, respectively). In both volumes,
      approximately 80% of the studies with nonsignificant unpaired t-tests contained
      at least one t-test with a type II error probability > 0.30. Our findings suggest
      that low power and a high incidence of type II errors are common problems in this
      journal. In addition, the presentation of statistics was often vague, t-tests
      were misused frequently, and assumptions for inferential statistics usually were
      not mentioned or examined.

PMID- 9249523
TI  - Noninvasive determination of pulse-wave velocity in mice.
AB  - Some transgenic mice have abnormal vascular function, but arterial geometry and
      dynamics are difficult to evaluate. To examine whether ultrasonic velocimetry
      could be used to determine arterial pulse-wave velocity (PWV) in mice, a custom
      made 20-MHz pulsed Doppler instrument was used to obtain blood flow velocity
      signals from the aortic arch and the abdominal aorta 4 cm downstream. The
      upstroke (foot) of the velocity wave was timed at each site with respect to the R
      wave of the electrocardiogram, and PWV was calculated by dividing the separation
      distance by the difference in R-foot times. Doppler determinations were compared
      with invasive tonometry, and PWV was altered pharmacologically. It was found that
      the upstrokes of pressure (by tonometry) and velocity were coincident (+/-1 ms)
      and that PWV could be calculated by either method on exposed vessels. With the
      use of Doppler methods, pulse transit time was determined noninvasively with +/-1
      ms resolution in 140 of 142 attempts in 82 mice. The calculated PWV in mice
      ranged from 220 to 850 cm/s with vasodilating anesthetics producing the low
      values and vasoconstricting agents producing the higher values. Thus PWV can be
      determined noninvasively in mice, is similar to that in other mammals, and
      responds as expected to vasoactive agents.

PMID- 9249525
TI  - 17 beta-Estradiol attenuates endotoxin-induced excessive nitric oxide production
      in ovariectomized rats in vivo.
AB  - Experiments were designed to examine the effect of 17 beta-estradiol on
      lipopolysaccharide (LPS)-induced excessive nitric oxide production in vivo.
      Ovariectomized and sham-operated female rats were injected with LPS (5 mg/kg ip),
      and different groups of ovariectomized, LPS-injected animals were treated with
      either 17 beta-estradiol, dexamethasone, or aminoguanidine. Nitric oxide
      generation was estimated by measuring plasma nitrite levels 12 h after LPS
      injection. LPS treatment of the rats resulted in a four- to fivefold increase in
      circulating plasma nitrite level, significantly higher in the ovariectomized
      animals compared with the sham-operated animals. The LPS-induced plasma nitrite
      increase could be prevented by dexamethasone (3 mg/kg ip) injected 1 h before LPS
      treatment. 17 beta-Estradiol (3 micrograms/rat sc), administered 48 h before LPS
      treatment, significantly attenuated the LPS-induced elevation in plasma nitrite
      levels. This effect was comparable to that achieved by aminoguanidine (200
      microM/kg), an inhibitor of inducible nitric oxide synthase, injected 1 h after
      LPS treatment. The present findings suggest that estrogens may be beneficial in
      pathological conditions associated with excessive nitric oxide generation.

PMID- 9249524
TI  - A novel cardioprotective function of adenosine A1 and A3 receptors during
      prolonged simulated ischemia.
AB  - The possible cardioprotective roles of adenosine A1 and A3 receptors were
      investigated in a cardiac myocyte model of injury. The adenosine A3 receptor is a
      novel cardiac receptor capable of mediating potentially important
      cardioprotective functions. Prolonged hypoxia with glucose deprivation was used
      to simulate ischemia and to induce injury in cardiac ventricular myocytes
      cultured from chick embryos 14 days in ovo. When present during the prolonged
      hypoxia, the adenosine A3 agonists N6-(3-iodobenzyl)adenosine-5'-N
      methyluronamide (IB-MECA) and 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N
      methyluronamide (CI-IB-MECA) caused a dose-dependent reduction in the extent of
      hypoxia-induced injury as manifested by a decrease in the amount of creatine
      kinase released and the percentage of myocytes killed. The adenosine A1 agonists
      2-chloro-N6-cyclopentyladenosine (CCPA), N6-cyclohexyladenosine, and adenosine
      amine congener were also able to cause a decrease in the extent of myocyte
      injury. The A1 receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine
      blocked the cardioprotective effect of the A1 but not of the A3 agonists.
      Conversely, the selective A3 antagonists MRS-1191 and MRS-1097 blocked the
      protection induced by CI-IB-MECA but had minimal effect on that caused by CCPA.
      Thus the cardioprotective effects of A1 and A3 agonists were mediated by their
      respective receptors. This study defines a novel cardioprotective function of the
      cardiac A3 receptor and provides conclusive evidence that activation of both A1
      and A3 receptors during hypoxia can attenuate myocyte injury.

PMID- 9249526
TI  - Role of the renal medulla in volume and arterial pressure regulation.
AB  - The original fascination with the medullary circulation of the kidney was driven
      by the unique structure of vasa recta capillary circulation, which Berliner and
      colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J.
      Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent
      exchange to concentrate large volumes of blood filtrate and produce small volumes
      of concentrated urine. We now believe we have found another equally important
      function of the renal medullary circulation. The data show that it is indeed the
      forces defined by Starling 100 years ago that are responsible for the pressure
      natriuresis mechanisms through the transmission of changes of renal perfusion
      pressure to the vasa recta circulation. Despite receiving only 5-10% of the total
      renal blood flow, increases of blood flow to this region of the kidney cause a
      washout of the medullary urea gradient and a rise of the renal interstitial fluid
      pressure. These forces reduce tubular reabsorption of sodium and water, leading
      to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he
      named "hormones," importantly modulate this pressure-natriuresis response by
      altering both the sensitivity and range of arterial pressure around which these
      responses occur. The vasculature of the renal medulla is uniquely sensitive to
      many of these vasoactive agents. Finally, we have found that the renal medullary
      circulation can play an important role in determining the level of arterial
      pressure required to achieve long-term fluid and electrolyte homeostasis by
      establishing the slope and set point of the pressure-natriuresis relationship.
      Measurable decreases of blood flow to the renal medulla with imperceptible
      changes of total renal blood flow can lead to the development of hypertension.
      Many questions remain, and it is now evident that this is a very complex
      regulatory system. It appears, however, that the medullary blood flow is a potent
      determinant of both sodium and water excretion and signals changes in blood
      volume and arterial pressure to the tubules via the physical forces that
      Professor Starling so clearly defined 100 years ago.

PMID- 9249527
TI  - Differentiated norepinephrine spillover in human skeletal muscle.
AB  - Most neurophysiological studies have shown similar sympathetic outflow to arm and
      leg. However, some direct microneurographic recordings indicate differentiated
      sympathetic outflow to limbs both at rest and during mental stress. Hence,
      differentiated levels of norepinephrine (NE) spillover could prevail. By steady
      state infusion of [3H]NE and body composition determination by dual-energy X-ray
      absorptiometry-scan, we simultaneously assessed arm and leg NE spillover related
      to 100 g tissue and total limb weight. NE spillover was lower in leg than arm
      (0.26 vs. 1.51 pmol.min-1.100 g-1, P < 0.05), and the difference remained when
      expressed as a function of total limb weight (66 vs. 137 pmol/min, P < 0.05).
      Fractional extraction of [3H]NE was similar in arm and leg. Neuronal uptake
      blockade by desipramine was more effective in leg than arm; fractional extraction
      in leg decreased by 32% (P < 0.05) but was unaltered in arm. Thus a lower NE
      spillover was observed from leg than arm, possibly reflecting a lower sympathetic
      outflow and a more neuronally dependent reuptake.

PMID- 9249528
TI  - Intrinsic tone and passive mechanics of isolated renal arteries from virgin and
      late-pregnant rats.
AB  - The purpose of this study was to investigate whether there are alterations in the
      intrinsic properties of renal interlobar arteries during pregnancy. Renal
      interlobar arteries (internal diameter approximately 250 microns) from virgin and
      late-pregnant rats were mounted in a pressurized arteriograph system. Intrinsic
      tone was quantified as the percent difference in luminal diameter of each artery
      in the presence of physiological saline solution and while pharmacologically
      relaxed with papaverine. At pressures between 75 and 125 mmHg, tone was 35-50%
      less in arteries from pregnant rats (P < 0.05). Endothelial removal reduced tone
      in arteries from virgin rats but had no effect on arteries from pregnant rats.
      Analysis of stress-strain curves (rate constants: pregnant, 6.31 +/- 0.38;
      virgin, 7.81 +/- 0.78; P < 0.05) indicate that there is a decrease in arterial
      stiffness in gestation. Thus pregnancy is associated with a reduced intrinsic
      tone, possibly because of a reduction in an endothelial constrictor influence on
      the vascular smooth muscle in isolated rat renal interlobar arteries. This
      effect, coupled with the decreased arterial stiffness, demonstrates the
      significant arterial adaptation occurring during pregnancy.

PMID- 9249529
TI  - Acute depressor actions of angiotensin II in the nucleus of the solitary tract
      are mediated by substance P.
AB  - Angiotensin II stimulates release of substance P from medulla oblongata slices,
      and low doses of substance P or angiotensin II injected into the nucleus of the
      solitary tract (NTS) decrease heart rate and mean arterial pressure. In this
      study, angiotensin II (250 fmol in 30 nl) was injected into the NTS of halothane
      anesthetized male Sprague-Dawley rats before and after NTS injections of the
      substance P antagonist [Leu11, psi CH2NH-(10-11)]substance P (600 fmol in 60 nl).
      The substance P antagonist blocked the angiotensin II-induced hypotension and
      bradycardia (-16 +/- 3 mmHg and -24 +/- 7 beats/min before versus -0.3 +/- 1 mmHg
      and -2 +/- 3 beats/min after; P < 0.05). The depressor and bradycardic effects of
      glutamate were not altered by the substance P antagonist. In vitro receptor
      autoradiography showed that the substance P antagonist (10 or 100 microM) did not
      compete for 125I-labeled angiotensin II binding in the dorsal medulla, suggesting
      that the substance P antagonist does not interact directly with angiotensin II
      receptors. We conclude that the cardiovascular effects of angiotensin II in the
      NTS are mediated at least in part by substance P.

PMID- 9249530
TI  - Effect of aging on vasopressin and aquaporin responses to dehydration in Fischer
      344-brown-Norway F1 rats.
AB  - The plasma vasopressin (VP) response to 72 h of water deprivation is attenuated
      in 30-mo-old Fischer 344 (F344) rats relative to 4-mo-old rats. This appears to
      reflect an inability to increase VP synthesis. In contrast, elevated plasma VP
      has been reported in the Brown-Norway (BN) strain of rats secondary to reduced
      renal VP responsivity. The response to dehydration in the F1 cross of these
      strains (F344BNF1) was evaluated. Male rats, 4 and 30 mo old, were deprived of
      water for 72 h or allowed water ad libitum. In response to dehydration, plasma
      sodium and hematocrit were significantly increased in both young and aged rats (P
      < 0.05), but plasma VP, urine osmolality, and aquaporin 2 expression were only
      increased in the young rats (P < 0.05). Posterior pituitary content of
      immunoreactive VP was depleted in the young but not the old rats. Thus the aged
      F344BNF1 rats demonstrated a deficit in VP release in response to an apparently
      similar dehydration stimulus. This deficit was different from those previously
      reported for either the F344 or BN strains. Thus further studies are required to
      determine the abnormalities underlying this response.

PMID- 9249531
TI  - Endothelin-1 limits increases in blood flow to native and collateral-dependent
      myocardium.
AB  - We hypothesized that blood flow to collateralized and noncollateralized
      myocardium is improved by antagonism of endothelin (ET) A receptors. Coronary
      collateral development was stimulated by placing an ameroid constrictor around
      the left circumflex coronary artery (LCx; collateralized region) in 11 swine.
      After 35 +/- 2 days, the left anterior descending coronary artery (LAD;
      noncollateralized region) was autoperfused at constant pressure using blood from
      a femoral artery. In group 1 (n = 6) transmural blood flow was measured using
      radioactive microspheres in the LAD, LCx, and border regions (i.e., area between
      LAD and LCx) during pacing stress while vehicle (phosphate-buffered saline) was
      infused into the LAD coronary artery (pace 1). Approximately 55 min later, a
      second period of pacing (pace 2) was performed in the presence of ETA receptor
      antagonism (BQ-123; 5 mg.ml-1.min-1 ic). In the time control group (group 2, n =
      5) vehicle was infused during both pacing periods. Indexes of myocardial oxygen
      demand were similar between paces 1 and 2 in each group. Compared with the first
      pacing period, transmural blood flow (ml.100 g-1.min-1) was higher (P < 0.05)
      during ETA receptor antagonism (i.e., pace 2) in the LAD (105 +/- 8 vs. 139 +/-
      9), border (51 +/- 5 vs. 83 +/- 7), and LCx regions (22 +/- 3 vs. 41 +/- 4,
      respectively) in group 1. In group 2, while perfusion in the border (98 +/- 17
      vs. 103 +/- 16) and LCx regions (19 +/- 4 vs. 27 +/- 6) was similar in paces 1
      and 2, LAD transmural flow was greater (134 +/- 9 vs. 160 +/- 13; P < 0.05)
      during the second pacing period. However, the percent increase in LAD flow
      comparing pace 1 with 2 was greater (P < 0.05) in group 1 (39 +/- 6%) compared
      with group 2 (20 +/- 7%). These data suggest that during the stress of pacing
      blood flow to collateralized and noncollateralized myocardium is improved in the
      presence of ETA receptor blockade.

PMID- 9249532
TI  - Angiotensins stimulate catecholamine release from the chromaffin tissue of the
      rainbow trout.
AB  - Immunohistochemical and pharmacological techniques were utilized to investigate
      the relationships between angiotensins and catecholamine release from the
      chromaffin tissue of rainbow trout (Oncorhynchus mykiss). Double labeling with
      [Asp1, Ile5]angiotensin II-fluorescein isothiocyanate (ANG II-FITC) and anti
      dopamine beta-hydroxylase revealed specific ANG II binding sites on chromaffin
      cells. Injection (1 nmol/kg body wt) of either ANG II-FITC, [Asn1, Val5, Asn9]ANG
      I, [Asp1, Ile5, His9]ANG I, [Asn1, Val5]ANG II, [Asp1, Val5]ANG II, or [Asp1,
      Ile5]ANG II elicited catecholamine release from in situ perfusion preparations of
      the head kidney. Catecholamine release elicited by [Asn1, Val5]ANG II (10(-13) to
      10(-7) mol/kg body wt) was dose dependent, and the secretion of epinephrine (Epi)
      was greater than that of norepinephrine (NE). Relative to the results obtained
      with the [Asn1, Val5]ANG II treatment (1 nmol/kg body wt), Epi release was 72 and
      82% lower in response to injections (1 nmol/kg body wt) of [Asn1, Val5]ANG I
      [amino acid (AA) positions 1-7] and [Asn1, Val5]ANG I (AA 1-6), respectively.
      Pretreatment with either losartan (10(-5) M), PD-123319 (10(-5) M), or
      hexamethonium (10(-3) M) had no effect on [Asn1, Val5]ANG II-elicited
      catecholamine release. Pretreatment with captopril (10(-4) M) significantly
      reduced [Asn1, Val5, Asn9]ANG I-elicited Epi and NE release and decreased basal
      catecholamine release. These results provide direct evidence that angiotensins
      can elicit catecholamine release from the chromaffin tissue via specific ANG II
      binding sites and indicate that the synthesis of ANG II may be either local or
      systemic.

PMID- 9249533
TI  - Contribution of humoral systems to the short-term variability of blood pressure
      after severe hemorrhage.
AB  - The aim of this study was to generate hemorrhage-triggered fluctuations in blood
      pressure (BP) at low frequency (LF, < 0.2 Hz) in conscious rats and investigate
      with spectral analysis the relative roles of hemorrhage-activated catecholamines,
      the renin-angiotensin system (RAS), and arginine vasopressin (AVP) on the
      generation of these fluctuations. The individual contribution of these factors
      was assessed using a combination of the selective antagonists, prazosin,
      losartan, and Manning compound (AVPX). At rest, systolic BP (SBP) LF fluctuations
      were slightly increased by losartan. The mid-frequency (MF; 0.2-0.6 Hz)
      oscillations of SBP and diastolic BP (DBP) were decreased by prazosin alone or
      associated with AVPX or losartan. The high-frequency (HF; respiratory)
      oscillations of SBP were increased by prazosin, prazosin plus losartan, and
      prazosin plus AVPX. After severe hemorrhage (20 ml/kg), the spontaneous BP
      recovery was characterized by the occurrence of slow fluctuations of SBP and DBP,
      centered approximately 0.065 Hz, and by increases of MF (89%) oscillations of
      SBP. The HF component of SBP variability tended to be increased by blood loss.
      The occurrence of the SBP LF fluctuations was prevented when alpha 1-adrenergic
      activity was blocked by prazosin. These oscillations were always present, despite
      inhibition of angiotensin II, and were increased after inhibition of the AVP
      activity. Pretreatment with the specific inhibitors used in these studies favored
      the amplifying effect of hemorrhage on HF fluctuations while they prevented the
      postbleeding increase in MF oscillations. In conclusion, the present results show
      an association between the dependence of the postbleeding blood pressure level on
      catecholamines and the occurrence of slow fluctuations of BP. The buffering role
      of AVP suggests the establishment of a hierarchy between humoral systems in the
      genesis of the LF oscillations of BP, with the slow oscillations being generated
      by the main pressor system and being dampened by the other systems. The
      postbleeding rise in the MF component of SBP variability could be considered a
      reflection of the activations of both the sympathetic vasomotor drive and the
      RAS. The postbleeding increase in the HF component of BP variability was dampened
      by the activation of the humoral systems. These effects may reflect the low
      preload state due to hypovolemia.

PMID- 9249534
TI  - Long-term captopril treatment restores natriuresis after carotid baroreceptor
      activation in the SHR.
AB  - In anesthetized Sprague-Dawley rats, intermittent bilateral carotid artery
      traction (BilCAT) caused a transient decrease in mean arterial pressure (MAP) of
      28 +/- 3 mmHg and led to a progressive increase in sodium excretion (UNaV) that
      nearly doubled 45-90 min after initiation of the repetitive application of BilCAT
      (P < 0.001). This natriuresis was accompanied by an increase in glomerular
      filtration rate (GFR) from 2.70 +/- 0.3 to 3.2 +/- 0.3 ml/min (P < 0.001), no
      change in renal plasma flow [clearance of p-aminohippurate (PAH)], and an
      increase in the fractional excretion of lithium. Rats with bilateral renal
      denervation exhibited neither natriuresis nor an increase in GFR in response to
      BilCAT despite similar vasodepression caused by the maneuver. Normotensive Wistar
      Kyoto (WKY) rats responded to BilCAT like Sprague-Dawley rats, whereas
      spontaneously hypertensive rats (SHR) exhibited an exaggerated vasodepressor
      response to BilCAT (-51 +/- 3 mmHg) without increasing either UNaV or GFR.
      Separate groups of WKY and SHR were treated from 4 wk of age with captopril added
      to the drinking water at a concentration of 1 g/l. At 12-14 wk, both groups had
      lower MAP compared with untreated animals. Captopril treatment did not alter
      either the natriuretic response or the increase in GFR seen in untreated WKY
      after BilCAT, and the maneuver produced equivalent degrees of vasodepression as
      in controls. However, treated SHR now responded to BilCAT with increases in both
      UNaV and GFR that closely resembled the responses seen in Sprague-Dawley and WKY
      rats. These results suggest that BilCAT produces natriuresis through a pathway
      dependent on the renal nerves. This pathway does not function in untreated SHR
      despite similar vasodepression. Long-term treatment with captopril restores this
      reflex pathway in SHR, lending support to the concept that angiotensin II is
      critically linked to heightened sympathetic nerve activity and abnormal sodium
      metabolism in this strain.

PMID- 9249535
TI  - Protein-induced increase in urinary dopamine in normal and diabetic rats: role of
      catecholamine precursors.
AB  - Feeding and protein intake increase renal dopamine excretion (UDAV). Here the
      contribution of amino acids (AA), L-tyrosine (Tyr), and L-phenylalanine (Phe) to
      UDAV in conscious normal rats and in animals with streptozotocin (STZ)-induced
      (60 mg/kg) diabetes mellitus was investigated. Feeding a standard chow (17.3%
      protein) increased UDAV in normal rats over twofold compared with the fasted
      state, but the effect was completely abolished by feeding a low-protein (LP,
      0.03%) diet. In STZ rats, UDAV was equal to that of normal rats during the fasted
      periods but was higher in fed animals, resulting most likely from the higher
      protein intake of STZ rats. In another series, rats on LP diet were given AA
      solutions (7, 14, and 21 g.kg-1.24 h-1) by gastric tube, which dose dependently
      increased UDAV to 67.3 +/- 4.3, 91.1 +/- 5.0, and 129 +/- 17 nmol.kg-1.day-1,
      respectively, compared with tap water as vehicle control (H2O, 55.6 +/- 7.0
      nmol.kg-1.day-1). In rats kept without access to chow, administration of AA
      including Phe and Tyr (AAPT) increased UDAV twofold compared with H2O, whereas AA
      solution without Tyr and Phe did not change UDAV. Tyr or Phe alone increased UDAV
      to the same extent as observed in AAPT. Higher doses of Tyr further increased
      UDAV dose dependently but with saturation characteristics. UDAV of the animals
      that were in a slightly negative sodium balance was not correlated to renal
      sodium excretion. It is concluded that, in conscious rats, the increase in UDAV
      in response to feeding 1) depends on the supply of catecholamine precursors
      solely, 2) is dose dependent and saturable, and 3) is not affected by
      experimental diabetes mellitus.

PMID- 9249536
TI  - Effects of an eight-day space flight on microvibration and physiological tremor.
AB  - Microgravity was used to study accelerometrically recorded microvibration (MV)
      and postural tremor (PT) at reduced muscle tone on one cosmonaut before, during,
      and after an 8-day space flight on the Russian Mir station. MV of the relaxed
      forearm in the 1 g environment showed the typical 7- to 13-Hz resonance
      oscillations triggered by the heart beat. In 0 g, these pulsations shifted to
      below 5 Hz and the waveform became similar to an ultralow frequency acceleration
      ballistocardiogram. PT of the arm stretched forward showed an irregular waveform
      in 1 g. In 0 g, the higher-frequency components were reduced and again an
      ultralow frequency ballistocardiogram emerged. As a control, hand force tremor
      was recorded as well; it was not affected by the gravity condition. A second
      order analog with muscle stiffness (C) as parameter was used to evaluate the
      measurements. For MV it could be shown that cardiac impacts produce damped
      resonance oscillations when C is high enough (1 g). At low C (0 g), this
      resonance phenomenon is essentially filtered out. For PT both neuromuscular and
      cardiovascular forces produce an irregular output; when C is lowered (0 g) the
      higher-frequency content is strongly reduced. It is concluded that both MV and PT
      waveforms are sensitive to musculoskeletal stiffness, such that at the lowest
      stiffness achieved the cardiac impact dominates. In 1 g, the cosmonaut's data
      were not significantly different from the results in a control group (n = 6).

PMID- 9249538
TI  - Myoglobin enhances cardiac performance in antarctic icefish species that express
      the protein.
AB  - Channichthyid icefishes of Antarctica are unique among adult vertebrates. All
      icefish species lack hemoglobin and red blood cells in their circulating blood.
      All icefishes examined to date also lack the intracellular oxygen-binding protein
      myoglobin (Mb) in their oxidative skeletal muscles. However, some icefish species
      do express Mb in their heart ventricles. It is unknown whether Mb in those
      species in which it is present represents an evolutionary relic or has functional
      significance. To address this problem, we compared mechanical performance of
      isolated, perfused hearts from two species of icefish in which Mb is either
      present (Chionodraco rastrospinosus) or is absent (Chaenocephalus aceratus).
      Hearts were challenged with increasing afterload (2.5-4.0 kPa) under conditions
      of defined basal flow (approximately 100 ml.min-1.kg-1), in both the presence and
      absence of 5 mM sodium nitrite, a Mb poison. Unlike hearts from C. aceratus,
      which were unable to maintain a constant cardiac output under pressure loading,
      those from C. rastrospinosus retained a constant flow up to 3.5 kPa afterload. At
      the upper range of power outputs, hearts of Mb-lacking C. aceratus display
      greater oxygen utilization than those of Mb-containing C. rastrospinosus.
      Poisoning of Mb significantly impaired the ability of C. rastrospinosus hearts to
      face pressure loading without reduction in flow, whereas those of C. aceratus
      were refractory to the treatment. The results strongly support a functional role
      for Mb in the former species.

PMID- 9249537
TI  - Evidence for increased beta-adrenoreceptor responsiveness induced by 14 days of
      simulated microgravity in humans.
AB  - We studied hemodynamic responses to alpha- and beta-receptor agonists in eight
      healthy men before and after 14 days of 6 degrees head-down tilt (HDT) to test
      the hypothesis that increased adrenoreceptor responsiveness is induced by
      prolonged exposure to simulated microgravity. Steady-state infusions of
      isoproterenol (Iso) at rates of 0.005, 0.01, and 0.02 microgram.kg-1.min-1 were
      used to assess beta 1- and beta 2-adrenoreceptor responsiveness. Infusions of
      phenylephrine (PE) at rates of 0.25, 0.50, and 1.00 microgram.kg-1.min-1 were
      used to assess responsiveness of alpha 1-vascular adrenoreceptors. Slopes
      calculated from linear regressions between Iso and PE doses and changes in beat
      to-beat heart rate, blood pressure, and leg vascular resistance (occlusion
      plethysmography) for each subject were used as an index of alpha- and beta
      adrenoreceptor responsiveness. HDT increased the slopes of heart rate (1,056 +/-
      107 to 1,553 +/- 83 beats micrograms-1.kg-1.min-1; P = 0.014) and vasodilation (
      469 +/- 111 to -1,446 +/- 309 peripheral resistance units.microgram-1.kg-1.min-1;
      P = 0.0224) to Iso infusion. There was no alteration in blood pressure or
      vascular resistance responses to PE infusion after HDT. Our results provide
      evidence that simulated microgravity causes selective increases in beta 1- and
      beta 2-adrenoreceptor responsiveness without affecting alpha 1-vascular
      adrenoreceptor responses.

PMID- 9249540
TI  - Regulation of plasma leptin in mice: influence of age, high-fat diet, and
      fasting.
AB  - Mechanisms regulating circulating leptin are incompletely understood. We
      developed a radioimmunoassay for mouse leptin to examine the influence of age,
      dietary fat content, and fasting on plasma concentrations of leptin in the
      background strain for the ob/ob mouse, the C57BL/6J mouse. Plasma leptin
      increased with age [5.3 +/- 0.6 ng/ml at 2 mo (n = 23) vs. 14.2 +/- 1.6 ng/ml at
      11 mo (n = 15), P < 0.001]. Across all age groups (2-11 mo, n = 160), log plasma
      leptin correlated with body weight (r = 0.68, P < 0.0001), plasma insulin (r =
      0.38, P < 0.001), and amount of intra-abdominal fat (r = 0.90, P < 0.001), as
      revealed by magnetic resonance imaging. Plasma leptin was increased by a high-fat
      diet (58% fat for 10 mo) and reduced by fasting for 48 h. The reduction of plasma
      leptin was correlated with the reduction of plasma insulin (r = 0.43, P = 0.012)
      but not with the initial body weight or the change in body weight. Moreover, the
      reduction in plasma leptin by fasting was impaired by high-fat diet. Thus plasma
      leptin in C57BL/6J mice 1) increases with age or a high-fat diet; 2) correlates
      with body weight, fat content, and plasma insulin; and 3) is reduced during
      fasting by an action inhibited by high-fat diet and related to changes of plasma
      insulin.

PMID- 9249539
TI  - Stimulation of eating by the second messenger cAMP in the perifornical and
      lateral hypothalamus.
AB  - Despite intense study of neurotransmitters mediating hypothalamic controls of
      food intake, little is known about which second messengers are critical for these
      mechanisms. To determine whether adenosine 3',5'-cyclic monophosphate (cAMP)
      might participate in these mechanisms, we injected the membrane-permeant cAMP
      analog 8-bromo-cAMP (8-BrcAMP) hypothalamically in satiated rats. Injection of 8
      BrcAMP (10-100 nmol) into the perifornical (PFH) and lateral hypothalamus (LH)
      dose dependently stimulated food intake of up to 15.7 g in 2 h. Significantly
      smaller responses were obtained with thalamic injections. In contrast to the
      strong stimulatory effects of PFH and LH 8-BrcAMP, cAMP and 8-bromo-guanosine
      3',5'-cyclic monophosphate (100 nmol) were ineffective, suggesting a chemically
      specific, intracellular action. Consistent with this, combined PFH injection of 7
      deacetyl-7-O-(N-methylpiperazino)-tau-butyryl-forskolin dihydrochloride and 3
      isobutyl-1-methylxanthine, agents that increase endogeneous cAMP, stimulated
      eating of up to 9.9 g in 2 h. These results demonstrate that increases in PFH/LH
      cAMP can elicit complex, goal-oriented behavior, suggesting an important role for
      cAMP in hypothalamic mechanisms stimulating food intake.

PMID- 9249541
TI  - Neuroanatomic organization of the parasympathetic bronchomotor system in
      developing sheep.
AB  - We applied two complementary retrograde labeling techniques to characterize the
      organization of the brain stem neuronal network responsible for the vagal
      innervation of the trachealis muscle in developing sheep. Single neuronal
      labeling produced by injections of the beta-subunit of cholera toxin into the
      muscle in newborn lambs showed that airway vagal preganglionic neurons are
      located exclusively in the nucleus ambiguous and nucleus of the solitary tract.
      Transneuronal labeling produced by similar injections of the Bartha strain of the
      pseudorabies virus in sheep fetuses demonstrated that these airway vagal
      preganglionic neurons receive inputs from a small number of neurons in brain stem
      areas known to participate in premotor control of the respiratory muscles
      (ventral respiratory group), chemoreception (nucleus of the solitary tract and
      ventral medullary surface), and cardiovascular and respiratory regulation (raphe
      nuclei, ventrolateral medulla, and noradrenergic groups of the medulla and pons).
      We conclude that the vagal preganglionic neurons that project to airway smooth
      muscle are already integrated in the control of breathing before birth in sheep.

PMID- 9249542
TI  - Characteristics of renal Na(+)-D-glucose cotransport in the skate (Raja erinacea)
      and shark (Squalus acanthias).
AB  - We have investigated the properties of the skate (Raja erinacea) and shark
      (Squalus acanthias) kidney Na(+)-D-glucose cotransporters (SGLT) in uptake
      studies of radiolabeled substrates into isolated renal brush-border membrane
      vesicles (BBMV). Scatchard plot analysis of the substrate dependence revealed
      that the Na(+)-D-glucose cotransporter population is homogenous within each
      species. Skate BBMV showed a relatively high affinity for D-glucose [Michaelis
      constant (K(m)) = 0.12 mM] with an apparent coupling ratio of approximately 2 Na+
      to 1 D-glucose, whereas the shark transporter was much lower in affinity (K(m) =
      1.90 mM) and had a lower coupling ratio, more like 1 Na+ to 1 D-glucose. These
      characteristics resemble the properties of SGLT1 and SGLT2, which are known to
      coexist in the mammalian kidney. Inhibitor studies using sugar analogs and
      glucosides suggested structural differences of the D-glucose binding site among
      these transporters, whereas the hydrophobic transporter domains in the vicinity
      of the D-glucose binding site appeared to be similar. In the high-affinity skate
      system, D-glucose was recognized by hydrogen bonds to the hydroxy groups at C-2,
      C-3, and C-4 and by hydrophobic interaction with the C-6 methylene group. In
      contrast, the low-affinity shark system seemed to lack the hydrophobic
      recognition motif for the C-6 methylene group of D-glucose.

PMID- 9249543
TI  - Vasopressin and V1-receptor antagonists modulate the activity of NTS neurons
      receiving baroreceptor input.
AB  - Arginine vasopressin (AVP) may act as a neurotransmitter or neuromodulator in the
      solitary tract nucleus (NTS). To determine whether AVP influences the activity of
      NTS neurons receiving cardiovascular afferent input, we used single-unit
      extracellular recording combined with local microinjection to test the effects of
      AVP and V1-receptor antagonists (antAVP) on spontaneously active NTS neurons in
      anesthetized rats. Phenylephrine-induced increases in arterial pressure were used
      to identify neurons receiving baroreceptor input. Phenylbiguanide was used to
      stimulate chemosensitive cardiopulmonary receptors. AVP excited 31 of 81 NTS
      neurons tested and inhibited 15 of 81 neurons. AntAVP had independent effects on
      NTS neurons: in addition to blocking the effects of AVP, antAVP inhibited 26 of
      72 neurons but excited only 13. Eighty-two percent of NTS neurons receiving
      excitatory or inhibitory baroreceptor inputs responded to AVP; 61% of these were
      excited by AVP. Fifty-eight percent of neurons receiving cardiopulmonary receptor
      input responded to AVP. These results suggest that AVP in rat NTS has a tonic,
      predominantly excitatory influence on a significant proportion of baroreceptor
      related neurons.

PMID- 9249544
TI  - Change from beta- to alpha-adrenergic glycogenolysis induced by corticosteroids
      in female rat liver.
AB  - The conversion of beta- to alpha-adrenergic glycogenolysis by corticosteroids was
      studied in perfused livers of mature female rats. Isoproterenol stimulated
      glucose production more effectively in female rats than in male rats, but the
      difference in its stimulatory effect disappeared in adrenalectomized (ADX) rats,
      whereas it remained in adrenodemedulated rats. When ADX female rats were treated
      with dexamethasone sulfate, alpha-responses increased and beta-responses
      decreased, depending on the concentration of dexamethasone sulfate. The treatment
      of female rats with 1.5 mg/kg dexamethasone sulfate changed the levels of the
      alpha- and beta-responses to those observed in male rats, and the changes were
      associated with changes in the number of receptors. Although periodicity of
      changes in plasma corticosterone levels was observed in both male and female
      rats, the extent of circadian variations was significantly lower in female rats
      during the estrous cycle than in male rats. The variations in plasma
      corticosterone levels and in both alpha- and beta-responses after ovariectomy
      approached those in male rats. The results suggest that the level of plasma
      corticosterone might play an important role in the regulation of the relative
      levels of alpha- and beta-adrenergic responses in female rats.

PMID- 9249545
TI  - Identification of brown fat and mechanisms for energy balance in the marsupial,
      Sminthopsis crassicaudata.
AB  - The presence of brown adipose tissue (BAT) in marsupials is controversial because
      attempts to identify mitochondrial uncoupling protein (UCP) have been
      unsuccessful. Sminthopsis crassicaudata is a small nocturnal marsupial with an
      interscapular pad of adipose tissue. Electron microscopy revealed this tissue to
      have characteristics typical of BAT. GDP binding and UCP detection by immunoblot
      confirmed BAT. Expression of UCP was increased by cold exposure. When animals
      were placed from 28 to 15 degrees C, body temperature (Tb) decreased by 1.7
      degrees C within 30 min and a further 1.0 degree C by 90 min (P < 0.001) before
      stabilizing at these lower levels. When animals were returned to 28 degrees C, Tb
      increased within 30 min (P < 0.001) and returned to basal by 120 min. When
      animals were maintained at 15 degrees C with ad libitum food for 12 days, Tb (P <
      0.05), tail width (P < 0.04), and O2 consumption (P < 0.01) all decreased. The
      respiratory quotient increased (P < 0.001), indicating a change from fat to
      carbohydrate utilization. Food intake was unchanged, and body weight increased on
      day 1 (P < 0.01) before returning to baseline on day 3, remaining stable
      thereafter. These data suggest that although BAT is present in the marsupial S.
      crassicaudata, it may not be necessary for thermogenesis, at least in the short
      term. S. crassicaudata utilizes a plasticity in Tb and a change in substrate
      utilization to maintain energy balance and body composition without the need for
      an increase in metabolic rate or food consumption and without the need for
      torpor.

PMID- 9249547
TI  - Kidneys from normotensive donors lower blood pressure in young transplanted
      spontaneously hypertensive rats.
AB  - Single transplanted kidneys from spontaneously hypertensive rats (SHR) have been
      shown to elicit hypertension in genetically normotensive recipients. This study
      was designed to investigate the effects of single transplanted kidneys from
      genetically normotensive donors [Biobreeding (BB)/Ottawa Karlsburg (OK) rats] on
      blood pressure in SHR recipients. The following groups were formed: group 1 (n =
      11), SHR donors and SHR recipients; group 2 (n = 15), BB/OK donors and SHR
      recipients; and group 3 (n = 8), BB/OK donors and BB/OK recipients. Recipients
      received antihypertensive treatment (hydralazine) from weaning until renal
      transplantation at the age of 9 wk and immunosuppressive treatment (anti-CD4
      antibody and cyclosporine A) for 3 wk starting on the day of transplantation. Six
      weeks after transplantation, intra-arterially measured blood pressure and heart
      weight-to-body weight ratio were highest in group 1, intermediate in group 2, and
      lowest in group 3. There were no significant differences with respect to plasma
      urea and creatinine concentrations among the three groups. These results support
      the hypothesis that hypertension in renal-transplanted SHR depends in part on the
      genetic background of the transplanted kidney.

PMID- 9249546
TI  - Effects of inhalation anesthetics on parasympathetic reflex vasodilation in the
      lower lip and palate of the cat.
AB  - The present experiments were designed to examine the effects of inhalation
      anesthetics (isoflurane, halothane, and sevoflurane) on the parasympathetic
      reflex vasodilation in the lower lip and palate elicited by electrical
      stimulation of the central cut end of the lingual nerve in vagosympathectomized
      cats. Isoflurane (1.5%), halothane (1.0%), and sevoflurane (2.5%), each at a
      concentration of 1.0 minimum alveolar concentration, markedly suppressed the
      evoked blood flow increases in the lower lip, whereas nitrous oxide (70% in 30%
      oxygen) and morphine (2 mg/kg iv) did not. Prior administration of picrotoxin, a
      gamma-aminobutyric acid (GABA) antagonist (2 mg/kg iv), reversed the inhibitory
      effect of isoflurane on the parasympathetic reflex response. Decerebration had no
      significant effect on the isoflurane-induced inhibition. These findings suggest
      that there is a GABA-mediated suppressive mechanism acting on this
      parasympathetic reflex response; the sites at which inhalation anesthetics exert
      such an inhibitory action could be in the midbrain, pons, or medulla, but not in
      the hypothalamus or higher structure.

PMID- 9249548
TI  - LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient
      (db/db) mice.
AB  - Administration of endotoxin (lipopolysaccharide, LPS) induces profound anorexia.
      Injection of leptin decreases food intake in mice. Recently, we reported that LPS
      and cytokines increase leptin levels in hamsters. To further investigate the role
      of leptin in the LPS-induced anorexia, we administered LPS to leptin receptor
      deficient (db/db) and leptin-deficient (ob/ob) mice. We found that LPS caused
      anorexia in both db/db and ob/ob mice. As might be predicted if leptin had a role
      in anorexia, the db/db mice were somewhat resistant to LPS-induced anorexia.
      However the ob/ob mice were more sensitive to LPS-induced anorexia. No
      differences between db/db and ob/ob mice and their respective littermate were
      observed in circulating tumor necrosis factor levels after LPS. These data
      suggest that leptin per se is not essential for LPS-induced anorexia.

PMID- 9249550
TI  - Osmoregulatory inhibition of thermally induced cutaneous vasodilation in
      passively heated humans.
AB  - We examined the effect of increased plasma osmolality (P(osm)) on cutaneous
      vasodilatory response to increased esophageal temperature (T(es)) in passively
      heated human subjects (n = 6). To modify P(osm), subjects were infused with 0.9,
      2, or 3% NaCl infusions (Inf) for 90 min on separate days. Infusion rates were
      0.2, 0.15, and 0.125 ml.min-1.kg body wt-1 for 0.9, 2, and 3% Inf, respectively,
      which produced relatively similar plasma volume expansion. Thirty minutes after
      the end of infusion, subjects immersed their lower legs in a water bath at 42
      degrees C (room temperature 28 degrees C) for 60 min after 10 min of preheating
      control measurements. Passive heating without infusion (NI) served as time
      control to account for the effect of volume expansion. P(osm) (mosmol/kgH2O)
      values at the onset of passive heating were 289.9 +/- 1.4, 292.1 +/- 0.6, 298.7
      +/- 0.7, and 305.6 +/- 0.6 after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively.
      The increases in T(es) (delta T(es)) at equilibrium during passive heating (mean
      delta T(es) during 55-60 min) were 0.47 +/- 0.08, 0.59 +/- 0.08, 0.85 +/- 0.13,
      and 1.09 +/- 0.12 degrees C after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively,
      which indicates that T(es) at equilibrium increased linearly as P(osm) increased.
      delta T(es) required to elicit cutaneous vasodilation (delta T(es) threshold for
      cutaneous vasodilation) also increased linearly as P(osm) increased as well as
      the delta T(es) threshold for sweating. The calculated increases in these
      thresholds per unit rise in P(osm) from regression analysis were 0.044 degree C
      for the cutaneous vasodilation and 0.034 degree C for sweating. Thus the delta
      T(es) thresholds for cutaneous vasodilation and sweating are shifted to higher
      delta T(es) along with the increase in P(osm), and these shifts resulted in the
      higher increase in T(es) during passive heating.

PMID- 9249549
TI  - Role of brain angiotensin II in thirst and sodium appetite of sheep.
AB  - The contribution of brain angiotensin II (ANG II) to thirst and Na+ appetite of
      sheep was evaluated. Thirst was stimulated by water deprivation, intracarotid or
      intracerebroventricular infusion of ANG II, or intracarotid or
      intracerebroventricular infusion of hypertonic solution. Intracerebroventricular
      infusion, over 1-3 h, of the ANG II type 1 (AT1) receptor antagonist, losartan,
      decreased or abolished water intake caused by all of the stimuli tested.
      Intracerebroventricular infusion of ZD-7155, another AT1-receptor antagonist,
      blocked ANG II-induced water intake. Neither losartan nor ZD-7155 infused
      intracerebroventricularly altered the Na+ appetite of Na(+)-depleted sheep.
      Intracerebroventricular infusion of losartan over 3 h, however, did block the
      increase in water intake and the decrease in Na+ intake caused by
      intracerebroventricular infusion of hypertonic NaCl in Na(+)-depleted sheep.
      Intracerebroventricular infusion of the ANG II type 2 (AT2) receptor antagonist,
      PD-123319, over 1-3 h, did not alter ANG II-induced water intake or Na+ depletion
      induced Na+ intake. These results are consistent with the proposition that brain
      ANG II, working via AT1 receptors, is involved in the neural system controlling
      some aspects of physiological thirst and Na+ appetite. A role for AT2 receptors
      in physiological thirst or Na+ appetite is not supported by the present results.

PMID- 9249551
TI  - Frequency domain characteristics of muscle sympathetic nerve activity in heart
      failure and healthy humans.
AB  - The purpose of this study was to characterize oscillations in muscle sympathetic
      nerve activity (MSNA) in the frequency domain in healthy subjects and patients
      with congestive heart failure (CHF) and to relate these to blood pressure (BP),
      heart rate (HR), and breathing frequency. MSNA burst frequency was significantly
      greater in CHF [52 +/- 21 (n = 12) vs. 35 +/- 11 (n = 19) bursts/min, P < 0.05],
      whereas breathing frequency and HR were similar. There was no significant
      difference between CHF and healthy subjects in total power, harmonic power, and
      nonharmonic power in the MSNA spectrum from 0 to 0.5 Hz, but low frequency power
      (LF, 0.05-0.15 Hz, P < 0.05) was reduced in heart failure patients. There was
      less coherence between BP and MSNA in the LF range, but similar spectral power in
      both groups in the very LF (VLF, 0-0.05 Hz) and high frequency (0.15-0.5 Hz)
      ranges. The transfer of MSNA oscillations into BP in the VLF (P < 0.05) and LF (P
      < 0.02) ranges was significantly lower in CHF, but gains in the transfer function
      and in the coherence between BP and MSNA and in the coherence between respiration
      and MSNA were similar in the two groups. These observations indicate that
      modulation of MSNA by the arterial baroreflex and respiration is preserved in
      CHF. The loss of LF power in the MSNA signal may be due to impaired neuroeffector
      transduction. The higher sympathetic nerve firing rate in CHF would therefore
      appear to be caused by factors other than the loss of regulation by these two
      inhibitory influences.

PMID- 9249552
TI  - Peptide YY and the Y2 agonist PYY-(13-36) inhibit neurons of the dorsal motor
      nucleus of the vagus.
AB  - Peptide YY (PYY) is released by endocrine cells in the ileum in response to the
      presence of fatty acids in the intestinal lumen. Circulating PYY suppresses
      vagally mediated digestive functions as a consequence of direct action on neurons
      in the dorsal medulla. Recent evidence from our laboratory suggests that this PYY
      mediated inhibition of digestion occurs because of peptide action at the Y2-type
      receptor in the dorsal medullary region encompassing vago-vagal reflex circuitry.
      The present study describes the effects of PYY and the specific Y2 agonist
      peptide PYY-(13-36) on neurons of the dorsal motor nucleus of the vagus (DMN) in
      both the 1) intact in vivo and 2) in vitro brain stem slice preparation. Our
      results show that 50% of DMN neurons recorded under in vivo or in vitro
      conditions, including synaptic blockade, are inhibited by the application of PYY
      or PYY-(13-36). Approximately 45% are not affected, and only approximately 5% are
      activated. These results suggest that one of the principal means by which PYY
      suppresses digestive functions is by the direct inhibition of cholinergic vagal
      efferent neurons of the DMN via action at a Y2 receptor.

PMID- 9249553
TI  - Glutathione systems and anoxia tolerance in turtles.
AB  - Effects of anoxic submergence (20 h at 5 degrees C) and subsequent 24 h aerobic
      recovery on glutathione levels and the activities of glutathione-related enzymes
      were examined in six tissues of Trachemys scripta elegans. Anoxia exposure
      resulted in tissue-specific changes in enzyme maximal activities, the most
      dramatic being suppression of gamma-glutamyl transpeptidase (gamma-GTPase)
      activity in anoxic kidney to only 2% of control. Anoxia exposure also caused
      significant decreases in activities of liver and heart glutathione-S-transferase
      (GST) (by 25 and 42%), heart glutathione reductase (GR) (by 67%), liver gamma
      GTPase (by 71%), and red muscle glutaredoxin (GRN) (by 56%). By contrast, anoxia
      exposure increased the activities of GR in liver and red muscle (by 52 and 80%),
      glutathione synthetase (GS) in white muscle (by 300%), and GRN in white muscle
      (by 400%). During aerobic recovery after anoxia, GST activity decreased in red
      muscle, kidney, and brain (by 72, 56, and 39%); GR decreased in liver and red
      muscle (by 52 and 80%); and GRN fell in red muscle (by 56%). Other activities
      rose during recovery: GR in heart (by 64%), GS in heart and brain (by 200%), and
      gamma-GTPase in brain (by 63%). Tissue pools of total glutathione were high in
      comparison with other ectotherms. Levels decreased during anoxia in four organs
      to 49-67% of control values. During aerobic recovery the reduced glutathione-to
      oxidized glutathione ratio (GSH/GSSG) increased in heart, kidney, and brain,
      indicating that oxidative stress did not occur in these organs. Rather than
      maintaining high levels of glutathione in tissues to prevent oxidative stress
      during aerobic recovery, turtles sustain high GSH/GSSG by regulating the
      activities of glutathione-using enzymes.

PMID- 9249554
TI  - Discrete thalamic lesions attenuate winter adaptations and increase body weight.
AB  - The midline thalamus (e.g., the paraventricular thalamic nuclei and the reuniens
      nucleus) of Siberian hamsters and other mammals has been reported to contain
      specific binding sites for melatonin, a hormone that is essential for
      photoperiodically induced winter adaptations such as reproductive quiescence,
      loss of body weight, daily torpor, and the winter molt. The first experiment
      investigated whether the midline thalamus is necessary for these winter
      adaptations. Adult Siberian hamsters received discrete neurotoxic lesions of the
      paraventricular thalamic nuclei or the reuniens nucleus while under pentobarbital
      sodium-induced anesthesia. After recovery, the hamsters were monitored for winter
      adaptations while they were exposed to short photoperiods (10 h light/day) for 12
      wk at 22 degrees C then for 60 days at 7 degrees C. Lesions of the reuniens
      nucleus, but not of the paraventricular thalamic nuclei, significantly inhibited
      short photoperiod-induced loss of body weight and tended to increase food
      consumption and decrease daily torpor. The second experiment showed that lesions
      of the reuniens nucleus increased body weight gain compared with that in controls
      during exposure to long photoperiods at 22 degrees C for 16 wk. In summary, these
      findings show that the reuniens nucleus is an important site for regulation of
      body weight and suggest that lesions of the reuniens nucleus may attenuate winter
      metabolic adaptations by causing an increase in body weight.

PMID- 9249556
TI  - Localization of the vasopressin V1a and V2 receptors within the renal cortical
      and medullary circulation.
AB  - Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially
      reduces renal medullary blood flow through the stimulation of the vasopressin V1a
      receptor (V1aR). Studies have also shown that the vasopressin V2 receptor (V2R)
      may modulate AVP-mediated vasoconstriction. At present, the distribution of the
      V1aR and V2R within the renal cortical and medullary microcirculation has not
      been determined. This study was designed to localize the transcriptional and
      translational sites of the V1aR and V2R in microdissected intrarenal vascular
      segments from both the cortex and medulla, specifically the interlobar, arcuate,
      and interlobular arteries; afferent and efferent arterioles; glomeruli; and
      single outer medullary vasa recta capillaries using reverse transcription
      polymerase chain reaction and Western blot analyses. The results indicated that
      V1aR mRNA and proteins were present in the isolated cortical or medullary
      vasculature, but the V2R mRNA and proteins were not found. This study suggests
      that the vasoconstrictor action of AVP within the renal medulla is mediated
      through the V1aR and that the modulatory V2R-mediated vasodilation is probably
      through the release of paracrine hormones found within the renal interstitial or
      tubular cells.

PMID- 9249555
TI  - Angiotensinogen gene expression in adipose tissue: analysis of obese models and
      hormonal and nutritional control.
AB  - Synthesis of angiotensin II (ANG II) has recently been described in adipose cells
      and has been linked to regulation of adiposity. Angiotensinogen (AGT), the
      substrate from which ANG II is formed, was previously shown to be elevated in
      adipose tissue of obese (ob/ob and db/db) mice and regulated by nutritional
      manipulation. It is unknown, however, whether overexpression of adipose AGT can
      be extended to other models of obesity and whether hormonal and/or nutritional
      factors directly regulate AGT expression in adipocytes. We investigated these
      possibilities by analyzing AGT mRNA levels in adipose tissue of obese Zucker
      rats, viable yellow (Avy) mice, and humans and by treating 3T3-L1 adipocytes with
      insulin, glucose, and a beta-adrenergic agonist. We demonstrate that AGT mRNA is
      decreased by approximately 50 and 80%, respectively, in adipose tissue of obese
      vs. lean Zucker rats and Avy mice. We also report that AGT is expressed at
      variable levels in human adipose tissue. Finally, we show that AGT mRNA is
      upregulated by insulin and downregulated by beta-adrenergic stimulation in
      adipocytes.

PMID- 9249557
TI  - Structural and biochemical analyses of cardiac ventricular enlargement in cold
      acclimated striped bass.
AB  - We examined effects of temperature acclimation on ultrastructural characteristics
      of cardiac myocytes and maximal activities of metabolic enzymes in cardiac tissue
      of striped bass (Morone saxatilis). Ventricular mass and ventricular mass divided
      by body weight were significantly increased (29% and 40%, respectively) in
      animals acclimated to cold (5 degrees C) vs. warm temperatures (25 degrees C).
      Mean myocyte diameter was increased at cold temperature (3.47 +/- 0.14 vs. 2.98
      +/- 0.08 microns), which is sufficient to explain the increase in ventricular
      mass. Ventricular enlargement did not alter volume densities of mitochondria,
      myofibrils, protein concentration, or citrate synthase activity. Thus total
      volume of mitochondria and myofibrils increased proportionately with cardiac mass
      in cold animals. Activities of hexokinase (34%) and carnitine
      palmitoyltransferase (42%) increased in cold animals, suggesting positive
      compensation and increased aerobic capacity for utilization of glucose and fatty
      acids for energy production. Enlargement of the ventricle and an increased
      capacity for ATP production in striped bass may help compensate for kinetic
      constraints at cold temperatures and maintain circulatory support to oxidative
      axial musculature for swimming activity.

PMID- 9249558
TI  - Mechanism for changes in vasopressin during acute exposure at 3 atm abs air.
AB  - Plasma arginine vasopressin (AVP) concentration is reduced in human subjects
      during prolonged saturation dive exposures of 4 atmospheres absolute (atm abs)
      and greater. The objectives of the present study were to determine if AVP would
      be reduced in eight male subjects during a 1-h exposure of 3 atm abs air and, if
      so, to determine the mechanisms responsible for the AVP response. Assessments of
      transmural central venous pressure (central venous pressure-esophageal pressure)
      and cardiac volume measurements were made to evaluate the possible role of
      cardiopulmonary receptors on the AVP response. Also, plasma osmolality
      (P(osmol)), venous blood gases, and mean corpuscular volume (MCV) were determined
      to evaluate potential effects of osmoreceptor and other fluid shifts on AVP
      release. AVP decreased (P < 0.05) by 0.5 microU/ml at 3 atm abs, whereas the
      transmural central venous pressure and cardiac volume remained unchanged
      throughout the experimental periods. A significant reduction (P < 0.05) in
      P(osmol) (by approximately 3 mosmol/kgH2O) was detected at 3 atm abs. Therefore,
      we conclude that the reduction in P(osmol) may cause the reduction in AVP during
      exposure to 3 atm abs pressure. The reduction in P(osmol) without water intake
      requires the postulation of an internal source of water. We propose that the
      threefold increase (P < 0.01) in venous PO2 and concomitant decrease (P < 0.05)
      in venous MCV suggest that the red blood cell may contribute to hypotonicity at 3
      atm abs.

PMID- 9249559
TI  - Serotonergic afferents mediate activity-dependent entrainment of the mouse
      circadian clock.
AB  - The circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the
      hypothalamus receives serotonergic afferents from the midbrain raphe nuclei, but
      the functional role of this projection is unclear. In rodents, locomotor activity
      increases serotonin content in the SCN, and serotonergic agonists phase shift the
      circadian clock in a manner closely similar to voluntary bouts of vigorous
      exercise, suggesting that serotonergic afferents could be part of the activity
      dependent entrainment mechanism. We investigated this possibility by selectively
      lesioning serotonin terminals within and adjacent to the SCN by local
      microinjection of 5,7-dihydroxytryptamine in mice pretreated with desipramine.
      This treatment decreased serotonin content 96 +/- 1% and 5-hydroxyindole-3-acetic
      acid content below levels of detection (nearly 100%) but did not decrease
      norepinephrine content or neuropeptide Y immunoreactivity in the SCN. These
      lesions did not alter subsequent running activity levels, yet rendered mice
      unable to synchronize to a regularly scheduled 2-h wheel running paradigm that
      entrained sham-lesioned controls. Serotonin afferents are thus necessary for
      activity-dependent entrainment in the mouse.

PMID- 9249560
TI  - Na-K-2Cl cotransporters are present and regulated in simian eccrine clear cells.
AB  - In freshly dissociated rhesus palm eccrine clear cells, regulatory volume
      increase (RVI) was studied using image analysis as a measure of Na-K-2Cl
      cotransport activity. Pseudo-RVIs, as well as RVI during methacholine (MCh)
      induced cell shrinkage, were observed in clear cells and were inhibited by 100
      microM bumetanide or in Na-free medium, but were not inhibited by amiloride or
      ouabain. RVI in hypertonic medium and RVI after MCh-induced cell shrinkage were
      accelerated by adenosine 3',5'-cyclic monophosphate (cAMP)-elevating agents
      (forskolin+isoproterenol) and inhibited by phorbol ester. RVI in hypertonic
      medium was enhanced by a phosphatase inhibitor, okadaic acid. mRNA for Na-K-2Cl
      cotransporter (NaKCC) was demonstrated in freshly isolated rhesus sweat secretory
      coils by polymerase chain reaction (PCR) after reverse transcription using a set
      of primers derived from the published human NaKCC (hNaKCC) 1 sequence, i.e.,
      nucleotides 2,043-2,810. The deduced amino acid sequence of the PCR-amplified 767
      base pair segment was identical to that of hNaKCC 1 from a human colon cell line
      (T84). The data are interpreted to indicate that NaKCC, showing strong homology
      to secretory type hNaKCC 1, is present in rhesus eccrine secretory coils and may
      participate in the cotransport component of eccrine sweat secretion and cell
      volume regulation, especially during cholinergic stimulation. The data also raise
      the possibility that sweat gland NaKCC may be upregulated by cAMP-mediated
      protein phosphorylation and downregulated by protein kinase C.

PMID- 9249561
TI  - Free-running rhythms and light- and dark-pulse phase response curves for diurnal
      Octodon degus (Rodentia).
AB  - Only rarely have precise, short-duration light pulses been used to generate phase
      response curves (PRCs) in diurnal mammals as done for nocturnal mammals, and a
      dark-pulse PRC has never been generated for a diurnal mammal. In addition, the
      relationship between free-running rhythms in different light intensities and PRCs
      has not been explored in diurnal mammals. We examined these relationships in
      Octodon degus, a diurnal hystricomorph rodent. Male degus lengthened the
      circadian period (tau) and duration of daily activity (alpha) after an increase
      in light intensity from 0 (DD) to 250 lx, and tau was furthered lengthened when
      light intensity increased from 580 to 5,800 lx. To generate a light-pulse PRC,
      degus were housed in DD and exposed to 20-min light pulses (250 lx) and phase
      shifts recorded across the circadian day. Two different PRCs were generated in
      response to 20-min light pulses. The majority of animals produced significant
      phase delays between circadian time (CT) 0 and CT 6, phase advances between CT 13
      and CT 22, and a nonsignificant response period between CT 8 and CT 13. Two
      animals produced a PRC devoid of significant phase delays, producing only
      significant phase advances between CT 17 and CT 24. To generate a dark-pulse PRC,
      animals were moved to LL (580 lx) and exposed to 1-h dark pulses. After dark
      pulses degus produced significant phase delays between CT 20 and CT 8, advances
      from CT 10 to CT 17, and nonsignificant responses between CT 18 and CT 20. This
      is the first report of a PRC to dark-pulse stimuli for a diurnal mammal. Thus
      light- and dark-pulse PRCs can be generated in a comparable way to those of
      nocturnal rodents, and we conclude that nocturnal and diurnal rodents use similar
      photic signals to produce somewhat different PRCs.

PMID- 9249562
TI  - Mechanisms of vasodilation elicited by VIP in sterically stabilized liposomes in
      vivo.
AB  - The purpose of this study was to begin to determine the mechanisms underlying
      vasodilation elicited by vasoactive intestinal peptide (VIP) in sterically
      stabilized liposomes (SSL) in the in situ peripheral microcirculation. Using
      intravital microscopy, we found that suffusion of VIP in SSL (0.42 and 0.85 nmol)
      onto the hamster cheek pouch for 1 h elicited significant and prolonged
      concentration-dependent vasodilation (P < 0.05). Suffusion of VIP in SSL (0.1
      nmol) for 7 min elicited a qualitatively similar response, although its magnitude
      was significantly smaller than that elicited by 1 h of suffusion of VIP in SSL (P
      < 0.05). The VIP-receptor antagonist VIP-(10-28), but not the amino-terminal
      fragment VIP-(1-12), significantly attenuated and delayed the onset of VIP in SSL
      induced vasodilation (P < 0.05). The nitric oxide (NO) synthase inhibitor NG
      nitro-L-arginine methyl ester (L-NAME), but not NG-nitro-D-arginine methyl ester
      (D-NAME), abrogated VIP in SSL-induced responses. We conclude that VIP in SSL
      elicits significant and prolonged vasodilation in the in situ peripheral
      microcirculation, which is specific, partly receptor dependent, and partly
      transduced by the L-arginine/NO biosynthetic pathway.

PMID- 9249563
TI  - Renal oxygenases: differential contribution to vasoconstriction induced by ET-1
      and ANG II.
AB  - In the rat isolated perfused kidney, 5,8,11,14-eicosatetraynoic acid, an
      inhibitor of all pathways of arachidonic acid (AA) metabolism, diminished
      endothelin-1 (ET-1)- and angiotensin II (ANG II)-induced renal vasoconstriction
      by approximately 60-70%. We then examined the individual contribution of each
      oxygenase, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 (CYP)
      to the vasoconstrictor effects of ET-1 and ANG II. Inhibition of COX with
      indomethacin reduced by 30-40% the vasoconstrictor responses to ET-1 and ANG II.
      Inhibition of 12-LOX with baicalein and 5- and 12-LOX with 5,8,11-eicosatriynoic
      acid attenuated ANG II-induced renal vasoconstriction by approximately 40-60% but
      did not affect responses to ET-1. In contrast, 12,12-dibromododec-11-enoic acid
      (DBDD), an inhibitor of the CYP omega/omega 1-hydroxylase pathway, diminished ET
      1-induced renal vasoconstriction by 30-40%, an effect reproduced by depletion of
      CYP enzymes with CoCl2. Neither DBDD nor CoCl2 affected renal vasoconstriction
      elicited by ANG II. ET-1 increased efflux of 19- and 20-hydroxyeicosatetraenoic
      acid, an effect reduced by DBDD. Thus products of the COX and CYP pathways
      contribute to the renal vasoconstrictor response to ET-1, whereas COX- and LOX
      derived eicosanoids contribute to the response to ANG II, accounting for > or =
      80% of the vasoactivity of the peptides.

PMID- 9249564
TI  - Endothelin and nitric oxide interact to regulate stretch-induced ANP secretion.
AB  - The purpose of this study was to determine the nature of the permissive effect of
      atrial stretch on atrial natriuretic peptide (ANP) secretion and the mechanism
      for the rapid termination of endothelin (ET) signaling following the removal of
      ET-dependent stimuli. Basal ANP release was not affected by either an elevation
      or inhibition of nitric oxide (NO) activity, but stretch-stimulated ANP release
      was significantly reduced from 144 +/- 20% to -3 +/- 7% of the baseline by
      increased NO activity. Furthermore, while the response to ET alone at low
      pressure was 37 +/- 13% of the baseline ANP secretion rate (P > 0.05), this
      response increased to 137 +/- 27% (P < 0.05) when NO activity was blocked, a
      response equal to the control high-pressure response (144 +/- 20%). Thus the
      reduction in NO activity is a permissive effect of stretch, and NO can rapidly
      terminate an ET-stimulated ANP response. Therefore, stretch-induced ANP secretion
      is regulated by a reciprocal interaction between locally produced ET, which
      appears to increase, and NO, which appears to decrease.

PMID- 9249565
TI  - Effects of energy limitation on Ca2+ and K+ homeostasis in anoxia-tolerant and
      anoxia-intolerant hepatocytes.
AB  - To gain more insight into the mechanistic basis of anoxia tolerance and
      intolerance, a comparative study was conducted on calcium homeostasis in goldfish
      and trout hepatocytes subjected to different forms of energy limitation. Using
      the fluorescent Ca2+ indicator fura 2, we observed that both chemical anoxia and
      true anoxia led to an increase of the concentration of cytosolic free calcium
      (Ca2+i) in the anoxia-sensitive hepatocytes of rainbow trout, whereas Ca2+i was
      maintained at control levels in the anoxia-tolerant hepatocytes of goldfish.
      Various lines of evidence suggest an intracellular origin of the Ca2+ increase
      observed in trout cells. Cyclosporin A, a specific inhibitor of the mitochondrial
      permeability transition pore in mammalian cells, was ineffective in preventing
      the Ca2+ increase, whereas a high dose of fructose depressed the Ca2+ surge by
      approximately 50%. The latter effect was not accompanied by improvement of the
      energetic state of the cells. A comparison of chemical anoxia with true
      (physiological) anoxia revealed that both treatments affected energy metabolism
      to a similar degree in trout hepatocytes, whereas the decrease of ATP seen in
      goldfish hepatocytes during chemical anoxia was absent during true anoxia.
      Elevation of Ca2+i with the calcium ionophore A-23187 led to a decoupling of
      unidirectional K+ fluxes in both normoxic and anoxic trout cells, whereas in
      goldfish hepatocytes the coupling of K+ fluxes was not affected by the rise of
      Ca2+i.

PMID- 9249566
TI  - Dopamine and diltiazem-induced natriuresis in the spontaneously hypertensive rat.
AB  - An attenuated natriuretic response to dopamine and D1 agonists in genetic
      hypertension has been attributed to an uncoupling of the renal D1 dopamine
      receptor from its G protein-effector protein complex. We have reported that in
      normotensive Wistar-Kyoto (WKY) rats the natriuresis induced by calcium channel
      blockers is caused in part by activation of renal D1 dopamine receptors. We
      tested the interaction between the renal D1 receptor and a calcium channel
      blocker, diltiazem, infused into a renal artery of anesthetized spontaneously
      hypertensive rats (SHR) acutely loaded with 5% saline. Diltiazem produced a 50%
      increase in renal blood flow and nearly tripled absolute and fractional sodium
      excretion; urine flow rate more than doubled, but glomerular filtration rate did
      not change. However, the D1 receptor antagonist SKF-83742, which had no effect by
      itself, did not diminish the response to diltiazem. In a separate group of
      concurrent experiments, we found that the diltiazem-induced natriuresis was
      associated with a decrease in Na(+)-K(+)-adenosinetriphosphatase activity in the
      renal medulla of SHR. In contrast, in WKY rats, no changes were noted in the
      renal medulla but a decrease in Na(+)-K(+)-adenosinetriphosphatase activity was
      noted in the renal cortex. Diltiazem had no effect on urinary dopamine excretion
      in either rat strain. We conclude that diltiazem induces natriuresis differently
      in SHR and WKY rats; it is independent of D1 receptors in SHR and is in great
      part mediated by renal hemodynamic, rather than by cortical tubular, effects.
      These studies support previous findings of a defective renal cortical tubular D1
      mechanism in SHR.

PMID- 9249567
TI  - Mechanisms in the pressor effects of hepatic portal venous fatty acid infusion.
AB  - Portal venous infusion of oleate solution has pressor effects. We have examined
      efferent mechanisms, measured the response to sustained infusion, and determined
      the effect of linoleate. Eight conscious animals received concurrent infusions of
      prazosin or vehicle with portal venous infusion of oleate. Oleate alone increased
      mean arterial pressure from 109.0 +/- 4.1 to 123.0 +/- 5.8 mmHg (P = 0.02),
      whereas no increase in blood pressure occurred when oleate was infused with
      prazosin. In 10 rats, concurrent infusion of losartan had no effect on the
      pressor activity of portal oleate infusion. Twenty-two animals received portal
      oleate or vehicle as a continuous infusion for 7 days. Mean arterial pressure
      (126.1 +/- 2.0 vs. 107.8 +/- 2.6 mmHg, P < 0.001) and heart rate (383 +/- 5 vs.
      366 +/- 5, P = 0.0257) were increased in oleate-infused animals. No differences
      in plasma fatty acids, glucose, insulin, pressor hormones, liver enzymes, or in
      vitro arterial pressor responsiveness were observed. Portal venous infusion of
      linoleate increased arterial pressure by 12.2 +/- 3.2 mmHg (P = 0.033). These
      results indicate that alpha-adrenergic activity is necessary for the acute
      pressor effects of portal oleate, that sustained portal oleate infusion results
      in persistent blood pressure elevation, and that other long-chain fatty acids
      besides oleate have pressor effects.

PMID- 9249568
TI  - Effects of alpha-adrenergic stimuli on mesenteric collecting lymphatics in the
      rat.
AB  - The present study examined the effects of alpha 1- and alpha 2-adrenergic stimuli
      on rat mesenteric collecting lymphatics in vivo. Sprague-Dawley rats were
      anesthetized, and the mesentery was prepared for intravital microscopic study.
      Mesenteric collecting lymphatic diameter was continuously monitored by using a
      computerized video tracking system, and indexes of lymphatic pumping (e.g.,
      contraction frequency, stroke volume, ejection fraction, and muscle shortening
      velocity) were determined from the diameter record. Contractile activity was
      monitored before and during the administration of various adrenergic agonists and
      antagonists. The receptor antagonists prazosin (alpha 1) and yohimbine (alpha 2)
      did not significantly alter baseline diameter or contractile activity, which
      suggests that lymphatics possess no basal adrenergic tone. Norepinephrine and
      phenylephrine (01-1.0 microM) produced dose-dependent increases in frequency and
      decreases in diameter. Lymphatic pump flow increased in direct proportion to
      frequency, because stroke volume did not change. The changes in lymphatic pumping
      produced by 1 microM norepinephrine were completely blocked by prazosin or
      phentolamine and only partially blocked by yohimbine. The alpha 2-adrenoceptor
      agonist (alpha-methyl-norepinephrine) produced no changes in lymphatic activity.
      This latter observation suggests that a role for postjunctional alpha 2
      adrenoceptors in modulating mesenteric lymphatic smooth muscle is unlikely. The
      results of these studies support the existence of alpha-adrenoceptors on
      lymphatic smooth muscle. It is concluded that conditions characterized by
      increased sympathetic outflow may augment lymphatic function through alpha 1- but
      not alpha 2-adrenoceptors.

PMID- 9249569
TI  - Metabolic correlates of selection for swim stress-induced analgesia in laboratory
      mice.
AB  - The upper limits of metabolic rates and the links between maximal and resting
      metabolic rates in vertebrates have recently received a lot of attention, mainly
      due to their possible relationship to the evolution of endothermy. We measured
      peak metabolic rates during 3 min swimming in 20 degrees C water (Vo2swim),
      maximal metabolic rate (Vo2max) in -2.5 degrees C Helox, and basal metabolic rate
      (BMR) in two lines of mice selected for high (HA) and low (LA) swim stress
      induced analgesia (SSIA). We found that exercise combined with heat loss used for
      producing SSIA also acted as a selection agent, resulting in a 15% HA/LA line
      difference in Vo2swim. Core body temperature of HA mice (characterized by lower
      Vo2swim) was also on average 3.2 degrees C lower than that of LA mice.
      Furthermore, Vo2max of HA mice was lower than that of LA mice by 8% and
      accompanied by larger hypothermia. Thus mice with exceptionally high (or low)
      Vo2max tended to have exceptionally high (or low) Vo2swim, resulting in a
      positive correlation between Vo2swim and Vo2max. All these suggest that selection
      for SSIA produced genetically correlated responses in both Vo2swim and Vo2max.
      However, we did not observe HA/LA differences in BMR. Hence, changes in resting
      and maximum metabolic rates are not necessarily correlated. We hypothesize that
      the lack of such a correlation was partially due to the modulation of metabolic
      responses by SSIA.

PMID- 9249570
TI  - Induction of cardiac natriuretic peptide gene expression in rats trained in
      hypobaric hypoxic conditions.
AB  - Adaptation of cardiac muscle to prolonged hypobaric hypoxia (770-740 mbar, 2,250
      2,550 m), endurance training, and their combination was studied in rats by
      investigating the gene expression of atrial natriuretic peptide (ANP) and B-type
      natriuretic peptide (BNP) in atria and ventricles. Rats were assigned into the
      following groups according to the barometric conditions and physical activity;
      normobaric sedentary (NS), normobaric training, hypobaric sedentary (HS), and
      hypobaric training (HT). Experimental periods were 10, 21, and 56 days; the
      groups at 91 days served as recovery groups from exposure to and training in
      normobaric and hypobaric conditions for 56 days. The right ventricular
      hypertrophy in HT rats at 10 days and 56 days was associated with elevated BNP
      mRNA levels (2.1- and 1.7-fold, P < 0.05, respectively), whereas hypobaric
      exposure without training was not sufficient to significantly increase
      ventricular BNP gene expression, although it lead to hypertrophy of the right
      ventricle. Right and left atrial BNP mRNA levels were also increased (up to 3.9
      fold, P < 0.01) in 10-day HS and 10-day HT groups. ANP mRNA levels in right
      ventricle and left ventricular epicardium were over twofold higher (P < 0.05
      0.01) in 10-day HS and 10-day HT groups in comparison to 10-day NS group. Plasma
      immunoreactive ANP concentration was increased (P < 0.05) in both hypobaric
      groups up to 21 days. The results show that exposure to hypobaric hypoxia itself
      and endurance training in hypobaric, hypoxic conditions lead to a marked early
      increase in ventricular and atrial ANP and BNP mRNA levels. The adaptational
      response to hypoxia was more pronounced when the oxygen availability was lowered
      additionally by endurance training carried out in hypobaric hypoxic conditions.

PMID- 9249571
TI  - Association of insulin-like growth factor mRNA expressions with muscle
      regeneration in young, adult, and old rats.
AB  - The purpose of this study was to determine whether impaired regeneration of
      skeletal muscle in old rats can be attributed to diminished expression of insulin
      like growth factor (IGF) mRNAs. Fischer 344 male rats aged 2 (young), 12 (adult),
      and 24 mo (old) were given an injection of the myotoxic anesthetic, bupivacaine,
      into the left tibialis anterior muscle. Muscle mass and protein concentration
      recovered to contralateral control values by 28 days in young, but not adult or
      old rats. The temporal and maximal expressions of IGF-I mRNA were similar during
      recovery from bupivacaine on days 5 and 10 in young, adult, and old rat muscles.
      IGF-I mRNA levels were reduced toward control levels in young rats by 15 days,
      but remained elevated in adult and old rats. IGF-I receptor mRNA in bupivacaine
      injected muscle of old rats was elevated significantly higher than injected
      muscle of young and adult rats at recovery day 5. Five days after bupivacaine
      injection, IGF-II mRNA was increased 46-fold in young rats but was only increased
      fourfold in adult rats. Thereafter, IGF-II mRNA expression was similar for young,
      adult, and old rats at 10 and 15 days of recovery. In summary, we demonstrate
      that impaired regeneration of the tibialis anterior muscle in adult or old rats
      after bupivacaine-induced damage is associated with a prolonged elevation of IGF
      I mRNA expression and/or diminished initial IGF-II mRNA expression.

PMID- 9249572
TI  - Vitamin B12 enhances GABA content but reduces glutamate content in the rat
      suprachiasmatic nucleus.
AB  - The present study attempted to elucidate effects of vitamin B12 (VB12) on the rat
      suprachiasmatic nucleus (SCN), which is the locus of the circadian clock in
      mammals, by evaluating the contents of its major neurotransmitters, gamma
      aminobutyric acid (GABA) and glutamate (Glu). First, contents of these amino
      acids were analyzed from tissue samples prepared at three different circadian
      times (CTs) in free-running rats under constant dim illumination. The content of
      GABA was highest in the middle of the resting phase (CT 6), intermediate early in
      the active phase (CT 14), and lowest late in the active phase (CT 20), whereas
      Glu content indicated inverse circadian variations. Subsequently, effects of
      intracerebroventricularly infused VB12 were assayed at CT 20. Compared with the
      saline-infused control, the infusion of VB12 (30 nmol/30 microliters) at CT 12-15
      significantly increased GABA content but decreased Glu content. The quantitative
      balance of these amino acids after VB12 infusion was similar to that at CT 6 in
      noninfused rats. These results suggest that infusion of VB12 to active rats
      shifts the ratio of SCN neurotransmitters toward that observed in resting rats.

PMID- 9249573
TI  - Nocturnal melatonin onset is phase locked to the primary sleep gate.
AB  - In this study, we used the "ultrashort sleep-wake paradigm" (7/13), which
      measures sleep propensity three times an hour for 29 h, from 0700 to 1200 the
      next day, on 6 healthy male subjects concomitantly with melatonin plasma level.
      Melatonin was measured once an hour during the morning and early afternoon of the
      first day and three times an hour from 1600 to 1000 the following morning. Rectal
      temperature was measured continuously for four subjects. Subjects underwent the
      7/13 paradigm three times, and in all three sessions consistent phase
      relationships were found between the nocturnal onset of melatonin secretion and
      opening of the nocturnal sleep gate; also, there was an inverse relationship
      between melatonin and core body temperature and an almost perfect out-of-phase
      relationship between sleep propensity and temperature, with the temperature peak
      falling precisely in the middle of the "forbidden zone" for sleep, i.e., the
      early evening nadir in sleepiness. On the basis of these phase relationships and
      previous findings from our laboratory on the effects of exogenous melatonin on
      the sleep propensity function, we conclude that melatonin participates in sleep
      wake regulation in humans.

PMID- 9249575
TI  - Time course of milk accumulation-induced opening of mammary tight junctions, and
      blood clearance of milk components.
AB  - Eight cows in early lactation were used to study the effect of milk accumulation
      on the state of mammary tight junctions and to examine alpha-lactalbumin as an
      indicator of tight junction permeability in vivo. During three successive
      periods, the cows were milked twice (4 days), once (6 days), and twice daily (4
      days). Plasma lactose, alpha-lactalbumin, and milk sodium concentrations were
      used as indicators of tight junction permeability. Furthermore, four cows were
      used to study the clearance of lactose and alpha-lactalbumin from the blood. Milk
      yield during once-daily milking decreased by 15.4% (P < 0.001). All indicators of
      mammary tight junction patency increased (P < 0.05) transiently during once-daily
      milking and indicated that tight junctions opened after approximately 18 h.
      Plasma alpha-lactalbumin and lactose were highly correlated (r = 0.82, P <
      0.001), indicating the suitability of plasma alpha-lactalbumin as an indicator of
      tight junction status in vivo. Clearance of alpha-lactalbumin and lactose from
      the blood was best described by a biexponential model. Elimination half-lives for
      lactose and alpha-lactalbumin were 44 and 40 min, respectively. This study showed
      that milk stasis during early established lactation induces tight junctions to
      switch to a leaky state after approximately 18 h and to revert to the closed
      state shortly after milking.

PMID- 9249574
TI  - Acute alterations in growth hormone-insulin-like growth factor axis in humans
      injected with endotoxin.
AB  - The purpose of the present study was to characterize the acute changes in the
      insulin-like growth factor (IGF) system in humans after administration of
      endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected
      intravenously into healthy adults, and serial blood samples were collected for
      the next 5 h; subjects injected with saline served as time-matched controls. LPS
      administration resulted in a gradual decrease in the total extractable IGF-I
      concentration, which was reduced by approximately 20% over the final 2 h of the
      experiment; levels of free IGF-I were not significantly altered. LPS also
      produced a marked but transient elevation in growth hormone (GH) concentration.
      IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS
      injection, and thereafter levels gradually returned toward baseline. IGFBP-2
      concentration also increased after LPS injection, but the maximal increase
      (approximately 50% above basal) was observed during the final 2 h of the
      protocol. In contrast, IGFBP-3 levels did not vary over the period examined in
      response to LPS, and there was no apparent increase in number of BP-3 proteolytic
      fragments. Cortisol levels were increased early and remained two- to threefold
      above baseline throughout the protocol. No significant alterations in serum
      concentration of glucose or insulin were noted. LPS also produced an early
      elevation in tumor necrosis factor and a later increase in interleukin-6. These
      data indicate that the acute changes in the GH-IGF axis in humans in response to
      LPS are comparable with those observed in humans in other traumatic conditions
      and in animal models of endotoxemia and infection.

PMID- 9249576
TI  - Acid stress induces a D1-like dopamine receptor in pituitary MSH cells of
      Oreochromis mossambicus.
AB  - A 7-day exposure of tilapia (Oreochromis mossambicus) to water with a pH of 4.5
      activates their pituitary melanophore-stimulating hormone (MSH) cells to
      preferentially release diacetyl alpha-MSH as an important corticotrope (13). We
      here focus on the control of alpha-MSH release by dopamine in tilapia exposed to
      water with low pH ("low-pH tilapia"). The MSH cells of low-pH tilapia showed a
      decreased sensitivity to inhibitory concentrations (10(-7)-10(-5) M) of dopamine
      compared with controls. Low concentrations (10(-14)-10(-8) M) of dopamine
      stimulated the release of alpha-MSH in low-pH tilapia but not in controls. Strong
      pharmacological evidence for a stimulatory dopamine receptor (D1-like) was
      obtained: the D1-agonists SKF-38393 and 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzazep ine hydrobromide (6-chloro APB) had a
      stimulatory effect on the release of alpha-MSH in low-pH tilapia MSH cells but
      not in controls. The selective D2-agonists quinpirole and 2-hydroxy apomorphin
      inhibited the release of alpha-MSH in controls as well as in low-pH tilapia, and
      there was no difference in the sensitivity of the cells to these agonists. We
      conclude that only MSH cells of low-pH exposed tilapia exhibit a D1-like receptor
      activity. A comparable D2-like receptor activity, as demonstrated by specific D2
      receptor agonists, is present in both controls and low-pH-adapted fish. The
      apparent loss of sensitivity of the MSH cells to inhibitory concentrations of
      dopamine, therefore, must be caused by the activation of the D1-like receptors
      and not by changes in the activity of the D2-like receptor proper. Stimulatory
      concentrations of dopamine not only quantitatively but also qualitatively
      enhanced the corticotropic activity of the released alpha-MSH, as indicated by
      the elevated ratio of diacetyl and monoacetyl alpha-MSH. This effect was mimicked
      by the D1-like agonists SKF-38393 and 6-chloro APB, indicating that the D1-like
      receptor activity is responsible for the enhancement of the di/mono ratio.

PMID- 9249577
TI  - Central injection of physostigmine attenuates exercise-induced pressor response
      in conscious cats.
AB  - The effects of intracerebroventricular administration of physostigmine, a
      cholinesterase inhibitor, on the cardiovascular responses evoked by static
      voluntary exercise were investigated using conscious cats. Four cats were trained
      to press a bar (200-650 g) with one forelimb for at least 20 s. The changes in
      mean arterial pressure (MAP), heart rate (HR), and developed force during the
      first five trials in 30 min by each individual cat were averaged, and a mean of
      the four values was then calculated. After the cats exercised for 30 min, either
      artificial cerebrospinal fluid (CSF) or physostigmine (5 micrograms) was
      administered intracerebroventricularly. Before physostigmine, exercise trials by
      the cats increased MAP and HR by 17 +/- 3 mmHg and 42 +/- 4 beats/min,
      respectively. Administration of physostigmine did not alter the resting MAP and
      HR but attenuated the MAP and HR responses to exercise (5-30 min
      postphysostigmine: MAP = 8 +/- 3 mmHg, HR = 25 +/- 7 beats/min; 30-60 min
      postphysostigmine: MAP = 4 +/- 3 mmHg, HR = 19 +/- 8 beats/min).
      Intracerebroventricular administration of CSF had no effect on the cardiovascular
      responses to static exercise. Pretreatment with the muscarinic antagonist,
      atropine (25 micrograms icv), blocked the attenuating effects of subsequent
      intracerebroventricular administration of physostigmine. These results
      demonstrate that stimulation of central muscarinic receptors attenuates the
      cardiovascular responses to static exercise by conscious cats. In addition, the
      present study suggests that there is no tonic effect of central muscarinic
      receptors on the cardiovascular responses to voluntary exercise.

PMID- 9249578
TI  - Physiological and cytokine responses in IL-1 beta-deficient mice after zymosan
      induced inflammation.
AB  - Interleukin (IL)-1 beta-deficient (IL-1 beta -/-) mice exhibited decreased
      zymosan-induced lethality and reduced production of IL-6 compared with wild-type
      controls (IL-1 beta +/+). In addition, IL-1 beta -/- mice had a diminished
      cellular infiltrate (33%) in the peritoneal cavity after zymosan. However,
      anorexia and hypoglycemia were not affected by the lack of IL-1 beta. The
      induction of corticosterone was only slightly reduced (14%) in IL-1 beta -/-
      mice. Peritoneal lavage fluid levels for IL-1 alpha, but not for tumor necrosis
      factor (TNF)-alpha, were also decreased. To evaluate the role of residual IL-1
      alpha production in IL-1 beta -/- mice, we used IL-1-receptor antagonist (IL
      1ra). In IL-1 beta +/+ mice, IL-1ra inhibited production of IL-6 after zymosan,
      without affecting TNF-alpha synthesis. There was no further inhibitory effect of
      IL-1ra on IL-6 production in IL-1 beta -/- mice, suggesting no role for IL-1
      alpha in zymosan-induced IL-6. Our results demonstrate that IL-1 beta plays a
      significant, although not exclusive, role in the physiological and cytokine
      responses to zymosan-mediated inflammation.

PMID- 9249579
TI  - The vagus nerve in the thermoregulatory response to systemic inflammation.
AB  - Experimentally, systemic inflammation induced by a bolus intravenous injection of
      lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory
      responses: monophasic fever (the typical response to low doses of LPS), biphasic
      fever (medium doses), and hypothermia (high doses). In our recent study
      [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely.
      Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic
      fever did not occur in subdiaphragmatically vagotomized rats. In the present
      work, we asked whether vagotomy affects the two other types of thermoregulatory
      response. Adult Wistar rats were vagotomized (or sham operated) and had an
      intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to
      the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000
      micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool
      (25 degrees C) environment. Three major results were obtained. 1) In the sham
      operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic
      fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C;
      this response was abated (no Tc changes) in the vagotomized rats. 2) At 30
      degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were
      represented by biphasic fevers (the higher the dose, the less pronounced the
      first and the more pronounced the second phase was); none of these biphasic
      fevers was altered in the vagotomized animals. 3) In response to the 1,000
      micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/-
      0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C)
      in the vagotomized rats. It is concluded that vagal afferentation may be
      important in the mediation of the response to minor amounts of circulating LPS,
      whereas the response to larger amounts is brought about mostly (if not
      exclusively) by nonvagal mechanisms. This difference may be explained by the dose
      dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals
      also appear to be more sensitive to the hypothermizing action of LPS in a cool
      environment; the mechanisms of this phenomenon remain speculative.

PMID- 9249581
TI  - NaCl ingestion ameliorates plasma indexes of calcium deficiency.
AB  - Rats deprived of dietary calcium ingest large volumes of concentrated NaCl
      solutions. To examine why, some physiological consequences of ingesting NaCl
      solution were measured. Male Sprague-Dawley rats fed diet containing 150 or 25
      mmol Ca2+/kg were killed at 20, 40, 80, or 160 min after they started to drink
      solutions of 0.125% saccharin+3% glucose (S+G), 50 mM CaCl2, or 300 mM NaCl.
      Relative to rats fed the 25 mmol Ca2+/kg diet given nothing to drink, those fed
      the same diet that drank NaCl or CaCl2 but not S+G had elevated plasma ionized
      calcium concentrations and reduced plasma parathyroid hormone (PTH)
      concentrations. Rats fed the 150 mmol Ca2+/kg diet did not show these changes. In
      a follow-up experiment, rats fed the 25 mmol Ca2+/kg diet that drank NaCl had
      elevated plasma ionized calcium and reduced PTH and 1,25-dihydroxyvitamin D
      concentrations over the following 4-6 h. An in vitro study found that plasma
      ionized calcium concentrations were modulated by NaCl concentration directly.
      These findings indicate that NaCl ingestion can temporarily enhance the calcium
      status of calcium-deprived rats.

PMID- 9249580
TI  - Vasodilator responses to acetylcholine, bradykinin, and substance P are mediated
      by a TEA-sensitive mechanism.
AB  - The effects of tetraethylammonium (TEA), a K+ channel antagonist, on vasodilator
      responses were investigated in the hindquarters vascular bed of the cat under
      constant-flow conditions. After administration of TEA in a total dose of 60 mg/kg
      into the hindquarters perfusion circuit, vasodilator responses to acetylcholine,
      bradykinin, and substance P were reduced, whereas vasodilator responses to the NO
      donors, diethylamine-NO complex, S-nitroso-N-acetylpenicillamine, and sodium
      nitroprusside, and to prostaglandin E1, albuterol, vasoactive intestinal
      polypeptide, isradipine, and levcromakalim were not altered. The inhibitory
      effect of TEA on responses to the endothelium-dependent vasodilators was
      reversible with time, and vasoconstrictor responses to norepinephrine, U-46619,
      angiotensin II, and BAY K 8644 were enhanced by the K+ channel antagonist.
      Although TEA had no sustained effect on baseline systemic arterial and
      hindquarters perfusion pressures, the NO synthase inhibitor, N omega-nitro-L
      arginine methyl ester, increased these pressures in the presence of TEA. The
      results of the present investigation suggest that TEA attenuates vasodilator
      responses to acetylcholine, bradykinin, and substance P by inhibiting the release
      of endothelium-derived relaxing factor. These data suggest that the acetylcholine
      , bradykinin-, and substance P-stimulated release of endothelium-derived relaxing
      factor may involve the opening of a TEA-sensitive K+ channel in the endothelium
      in the hindlimb vascular bed of the cat, but that a TEA-sensitive mechanism is
      not involved in the maintenance of baseline tone in this vascular bed.

PMID- 9249583
TI  - Intraportal mercaptoacetate infusion increases afferent activity in the common
      hepatic vagus branch of the rat.
AB  - Because dissection of the common hepatic vagus branch attenuated the feeding
      response to intraperitoneal injection of mercaptoacetate (MA), an inhibitor of
      fatty acid oxidation, in rats fed a fat-enriched diet (18% fat), the effect of MA
      on the discharge rate in afferents of the common hepatic vagus branch was
      investigated. Intraportal infusion of the Na salt of MA (200, 400, and 800
      mumol/kg) in rats adapted to the 18% fat diet dose dependently increased the
      discharge rate in afferents of the common hepatic vagus branch, whereas NaCl and
      the Na salt of the structurally related compound 2-mercaptopropionate had no
      effect. The lowest dose of MA yielding a significant increase in the discharge
      rate was 400 mumol/kg. This agrees with the dose dependence of the feeding
      response to MA. These findings are consistent with the notion that hepatic fatty
      acid oxidation controls food intake by modulating the discharge rate of vagal
      afferents.

PMID- 9249584
TI  - Postnatal development of the ob gene system: elevated leptin levels in suckling
      fa/fa rats.
AB  - The postnatal development of the ob gene system has been examined in Zucker fa/fa
      and +/fa plus +/+ (referred to as +/?) rats. White adipose tissue was taken from
      animals aged 1 to 28 days. Before weaning, white fat was predominantly
      subcutaneous, the amount increasing rapidly after birth. ob mRNA was detected by
      Northern blotting in samples of inguinal fat at 1 day of age and thereafter.
      Circulating leptin, measured by enzyme-linked immunosorbent assay, was also
      detectable from 1 day of age, the level rising to a peak by 10 days of age and
      then declining. The fa/fa genotype was determined from the size of the product
      after Msp I digestion of the Ob-receptor gene obtained by polymerase chain
      reaction amplification of genomic DNA. No statistically significant difference in
      ob mRNA level between fa/fa and +/? animals was obtained before 25 days of age.
      However, leptin levels were significantly higher in the fa/fa mutant by 10 days
      of age, despite the absence of any significant elevation in the weight of the
      major fat depots or in ob mRNA level. It is concluded that the ob gene is
      expressed and leptin produced early in postnatal life in rats; the elevation of
      circulating leptin in suckling fa/fa animals indicates that dysregulation of the
      leptin system occurs before the overt development of the obese phenotype.

PMID- 9249582
TI  - Intracellular pH response to hypercapnia in neurons from chemosensitive areas of
      the medulla.
AB  - We investigated whether neurons in two chemosensitive areas of the medulla
      oblongata [nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM)]
      respond to hypercapnia differently than neurons in two nonchemosensitive areas of
      the medulla oblongata [inferior olive (IO) and hypoglossal nucleus (Hyp)].
      Medullary brain slices from preweanling Sprague-Dawley rats were loaded with
      2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, and intracellular pH (pHi) was
      followed in individual neurons at 37 degrees C with the use of a fluorescence
      imaging system. Most neurons from the NTS and VLM did not exhibit pHi recovery
      when CO2 was increased from 5 to 10% at constant extracellular HCO3-
      concentration [extracellular pH (pHo) decreased approximately 0.3 pH unit]
      (hypercapnic acidosis). However, when CO2 was increased from 5 to 10% at constant
      pHo (isohydric hypercapnia), pHi recovery was seen. In contrast, all neurons from
      the IO and Hyp exhibited pHi recovery during hypercapnic acidosis. All pHi
      recovery in the four areas studied was inhibited by 1 mM amiloride and unaffected
      by 0.5 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. These data indicate
      that 1) pHi regulation differs between neurons in chemosensitive (NTS and VLM)
      and nonchemosensitive (IO and Hyp) areas of the medulla, 2) pHi recovery is due
      solely to Na+/H+ exchange in all four areas, and 3) Na+/H+ exchange is more
      sensitive to inhibition by extracellular acidosis in NTS and VLM neurons than in
      IO and Hyp neurons.

PMID- 9249585
TI  - GABA release in the dorsal raphe nucleus: role in the control of REM sleep.
AB  - The cessation of firing of serotonergic dorsal raphe neurons is a key controlling
      event of rapid eye movement (REM) sleep. We tested the hypothesis that this
      cessation of activity is due to gamma-aminobutyric acid (GABA) release using the
      in vivo microdialysis technique. We found that REM sleep is accompanied by a
      selective increase in GABA release, but not by a change in glutamate or glycine
      release in the dorsal raphe nucleus. Microinjection of the GABA agonist muscimol
      into the dorsal raphe increased REM sleep, although microperfusion of the GABA
      antagonist picrotoxin blocked REM sleep. These results implicate GABA release as
      a critical element in the production of the REM sleep state and in the control of
      discharge in serotonergic neurons across the sleep/wake cycle.

PMID- 9249586
TI  - Cellular and molecular mechanisms of renal peptide transport.
AB  - Renal epithelial cells express membrane transport proteins capable of cellular
      uptake of a large variety of di- and tripeptides. These transporters contribute
      to renal amino acid homeostasis and the efficiency of conservation of amino acid
      nitrogen. In addition, these transporters appear to play a role in the renal
      handling of xenobiotics that possess a peptide backbone. Peptide carriers
      specialized in transport of di- and tripeptides have been identified in bacteria,
      fungi, plants, and epithelial cells of mammalian intestine and kidney. They
      appear to represent an archaic transporter family conserved throughout evolution.
      As a unique feature, these peptide carriers utilize a transmembrane
      electrochemical proton gradient as the driving force that enables them to
      transport peptides against a concentration gradient. Renal peptide transporters
      have been characterized in terms of mechanism of transport function and substrate
      specificity in a number of model systems. Within the last two years, kidney
      peptide transporters of a variety of species have been identified by cloning
      techniques. In this review we discuss the physiological importance of renal
      peptide carriers and the transport mechanisms at the cellular level. We also
      present the recent advancements in functional expression of the cloned proteins
      that provide first insights into their molecular architecture and mode of
      operation.

PMID- 9249587
TI  - Induction of molecular chaperones by hyperosmotic stress in mouse inner medullary
      collecting duct cells.
AB  - The extreme hyperosmotic conditions that exist in the renal inner medulla enable
      the urinary concentrating mechanism to function. In this study, we evaluated
      whether stress-related molecular chaperones are induced in response to
      hyperosmotic stress in mouse inner medullary collecting duct (mIMCD3) cells.
      Exposure of cells to medium supplemented with 100 mM NaCl for 4 or 24 h resulted
      in an increase in heat shock protein-72 (HSP-72) (inducible form) by Western
      blot. Immunocytochemistry confirmed the increase of HSP-72 and showed that
      hyperosmotic stress resulted in a localization of HSP-72 predominantly to the
      nucleoplasm that surrounds the nucleoli and to the cytoplasm, a subcellular
      distribution pattern different from that seen with heat shock. Using a denatured
      protein (casein)-affinity column with ATP elution, we identified a number of
      putative molecular chaperones (46, 60, 78, and 200 kDa) that are upregulated in
      response to 4 h of hyperosmotic NaCl treatment. Microsequencing identified one of
      these proteins to be the mitochondrial chaperone mtHSP-70, a member of HSP-70
      family, and another to be similar to beta-actin. We also found high levels of HSP
      72 in cells chronically adapted to hypertonicity, indicating that chaperones are
      still required to maintain certain cellular functions even after nonperturbing
      organic osmolytes are known to accumulate. These results suggest an important
      role for molecular chaperones in the adaptation of renal medullary epithelial
      cells to the hyperosmotic conditions that exist in the inner medulla in vivo.

PMID- 9249588
TI  - Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary
      interstitial cells.
AB  - Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which
      mediate the conversion of arachidonate to prostaglandin H2. COX1 is the
      predominant constitutive isoform, whereas COX2 expression is typically low. In
      the present studies we cloned rabbit COX2 and determined its distribution in
      unstimulated tissues. Screening rabbit eye and uterine libraries yielded two
      cDNAs containing identical inserts with a 1,812-nucleotide open-reading frame.
      This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse
      COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid
      synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary
      bladder. COX2 expression was primarily in renal outer medullary interstitial
      cells with cortical expression in macula densa. In cultured medullary
      interstitial cells, COX2 mRNA predominated, with little COX1 expression.
      Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and
      epidermal growth factor but suppressed by dexamethasone. Phorbol ester also
      upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important
      implications for side effects of COX2-selective inhibitors.

PMID- 9249589
TI  - Recombinant insulin-like growth factor I normalizes expression of renal glucose
      transporters in diabetic rats.
AB  - By immunocytochemistry we have studied the effect of recombinant human insulin
      like growth factor I (rhIGF-I) on expression of renal GLUT-1, -2, and -5 in rats
      with streptozotocin (STZ)-induced diabetes. In the renal tubules of these rats,
      expression of GLUT-1 was reduced and that of GLUT-2 was increased. GLUT-1
      expression was restored, and GLUT-2 expression was normalized by 2-wk
      administration of rhIGF-I. We have shown that GLUT-5 was expressed at the brush
      border membrane of the proximal convoluted tubules (PCT) of the cortex and at the
      glomerular mesangial cells (GMC) in normal rat kidney. In the diabetic rats, GLUT
      5 expression was increased at both sites, along with an increase of GLUT-2
      expression at the basolateral membrane of PCT, and was decreased to normal level
      at both sites by treatment with rhIGF-I. Thus, like GLUT-2, GLUT-5 is suggested
      to regulate glucose reabsorption in PCT. The relationship between overexpression
      of GLUT-5 in GMC and accumulation of sorbitol and advanced glycosylation end
      products are discussed. Regulation of GLUT expression may play an important role
      on renal glucose homeostasis.

PMID- 9249590
TI  - Interactions of ultrapure bovine hemoglobin with renal epithelial cells in vivo
      and in vitro.
AB  - Using an ultrapurified hemoglobin (Hb) solution, we investigated the
      physiological effects and cellular processing of Hb in rat kidneys and in
      cultured opossum kidney (OK) cells. Rats infused with < 5.0 g/kg Hb showed no
      change in baseline serum creatinine (SCr) values (0.58 +/- 0.05 mg/dl) over 48 h,
      whereas transient acute renal failure followed infusion of 7.5 g/kg Hb (SCr 3.4
      +/- 1.02 mg/dl, P = 0.02). Histology of Hb-infused kidneys demonstrated tubular
      epithelial cell injury. Renal injury was not caused by volume or oncotic load,
      cardiovascular effect, or ATP depletion. After Hb infusion, heme oxygenase, the
      rate-limiting enzyme in Hb catabolism, was induced in an organ-specific fashion.
      Inhibiting heme oxygenase activity with cimetidine did not alter Hb renal injury.
      Using OK cells, we determined that renal epithelia process Hb by fluid-phase
      endocytosis. Proton permeability of fluorescein Hb endosomes was unaltered
      compared with fluorescein dextran controls, demonstrating that Hb does not alter
      endosomal membrane integrity. These data suggest that Hb renal injury in rats
      occurs following large doses of ultrapure Hb, does not alter early steps in Hb
      endosomal processing by renal epithelia, and involves a mechanism that is not
      heme oxygenase dependent.

PMID- 9249591
TI  - Alterations in dopamine DA1 receptor and G proteins in renal proximal tubules of
      old rats.
AB  - The present study examines the effect of dopamine DA1-receptor agonists on the
      renal proximal tubular Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase)
      activity and quantitates DA1 receptors and the coupled G proteins in Fischer 344
      model of adult (6 mo old) and old (23 mo old) rats. Dopamine and the preferential
      DA1-receptor agonist, SKF-38393, produced a concentration-dependent inhibition of
      Na(+)-K(+)-ATPase activity in proximal tubules from adult rats, whereas the
      enzyme activity was unaffected by these agonists in the old rats. The binding of
      DA1-receptor antagonist [3H]Sch-23390 in the proximal tubular basolateral
      membranes showed a marked decrease (approximately 47%) in the receptor numbers in
      old compared with adult rats, whereas dissociation constant (Kd) values in old
      compared with adult rats were not significantly different. Dopamine and SKF-38393
      stimulated 35S-labeled guanosine 5'-O-(3-thiotriphosphate) binding in adult rats,
      but there was no significant effect on the binding in the old rats.
      Quantification of G2 alpha and Gq/11 alpha using Western analysis revealed a
      significant increase in quantities of both the G proteins in old rats. The data
      suggest that a reduction in DA1 receptor number and subsequently reduced G
      protein activation may be the causative factors for the impairment in DA1
      receptor-mediated inhibition of Na(+)-K(+)-ATPase activity in the proximal
      tubules of old rats.

PMID- 9249593
TI  - Low permeabilities of MDCK cell monolayers: a model barrier epithelium.
AB  - Barrier epithelia such as the renal collecting duct (in the absence of
      antidiuretic hormone) and thick ascending limb, as well as the stomach and
      mammalian bladder, exhibit extremely low permeabilities to water and small
      nonelectrolytes. A cell culture model of such epithelia is needed to determine
      how the structure of barrier apical membranes reduce permeability and how such
      membranes may be generated and maintained. In the present studies, the
      transepithelial electrical resistance and isotopic water and urea fluxes were
      measured for Madin-Darby canine kidney (MDCK) type I and type II cells, as well
      as type I cells expressing the mucin protein, MUC1, in their apical membranes.
      Although earlier studies had found the unstirred layer effects too great to
      permit measurement of transepithelial permeabilities, use of ultrathin
      semipermeable supports in this study overcame this difficulty. Apical membrane
      diffusive water permeabilities were 1.8 +/- 0.4 x 10(-4) cm/s and 3.5 +/- 0.5 x
      10(-4) cm/s in MDCK type I and type II cells, respectively, at 20 degrees C. Urea
      permeability in type I cells at the same temperature was 6.0 +/- 0.9 x 10(-6)
      cm/s. These values resemble those of other barrier epithelial apical membranes,
      either isolated or in intact epithelia, and the water permeability values are far
      below those of other epithelial cells in culture. Transfection of MDCK type I
      cells with the major human urinary epithelial mucin, MUC1, led to abundant
      expression of the fully glycosylated form of the protein on immunoblots, and flow
      cytometry revealed that virtually all the cells expressed the protein. However,
      MUC1 had no effect on water or urea permeabilities. In conclusion, MDCK cells
      grown on semipermeable supports form a model barrier epithelium. Abundant
      expression of mucins does not alter the permeability properties of these cells.

PMID- 9249592
TI  - Involvement of phospholipase A2 in gentamicin-induced rat mesangial cell
      activation.
AB  - The role of the phospholipase A2 (PLA2) activation in the gentamicin (Gent)
      induced rat mesangial cell activation has been studied. Gent (10(-5) M) induced a
      time-dependent mesangial planar cell surface area reduction that was
      significantly inhibited by the PLA2 inhibitors aristolochic acid (AA) and
      quinacrine, by the platelet-activating factor (PAF) blocker BN-52021 (BN), and by
      verapamil. These substances also inhibited Gent-induced [3H]thymidine
      incorporation into DNA (AA, 504 +/- 20; quinacrine, 555 +/- 66; BN, 1,126 +/-
      120; and verapamil, 896 +/- 109; vs. 1,818 +/- 35 cpm/well in cells treated with
      Gent alone) and the Gent-induced increase in cell number (AA, 20,116 +/- 2,696;
      quinacrine, 24,687 +/- 1,481; BN, 26,122 +/- 1,016; and verapamil, 27,566 +/-
      1,214; vs. 47,486 +/- 1,124 cells/well in cells treated with Gent alone). Gent
      induced a twofold increase in [3H]acetate incorporation into PAF (27 +/- 3 vs. 12
      +/- 2 cpm/microgram protein in control conditions) that was completely blocked by
      AA, BN, or verapamil. Gent increased thromboxane B2 and prostaglandin E2 (PGE2)
      production, with both increases inhibited by either AA or verapamil. BN only
      inhibited the Gent-induced mesangial PGE2 production. In addition, Gent increased
      PLA2 activity (measured as [3H]arachiodonic acid release, 29,849 +/- 2,151 vs.
      20,104 +/- 2,308 cpm/well in basal conditions), an effect that was blocked by AA
      (11,804 +/- 684 cpm/well). These data suggest a major role for PLA2 activation in
      Gent-induced mesangial cell contraction, proliferation and prostanoid secretion.

PMID- 9249594
TI  - Plasma membrane calcium ATPase isoform expression in cultured rat mesangial
      cells.
AB  - The maintenance of intracellular ionized calcium (iCa2+) in the submicromolar
      range is important for mesangial cell (MC) function, and, as in most mammalian
      cells, plasma membrane Ca(2+)-ATPases (PMCA) play an important role in the
      homeostatic process. Molecular studies have demonstrated four PMCA isoforms, each
      with multiple splice variants. The present study examines the expression of PMCA
      isoforms and calmodulin-binding region splice variants in cultured MC from
      Sprague-Dawley rats and from spontaneously hypertensive rats (SHR) and Wistar
      Kyoto (WKY) rats before and after the onset of hypertension in SHR. Using reverse
      transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses, we
      have demonstrated PMCA1, -3, and -4, but not PMCA2, to be present in MC from
      these rat strains. Splice variant analysis revealed PMCA1a and -1b, PMCA3a, -3b,
      and -3c, and PMCA4a and -4b to be expressed in MC from all three strains. The
      relative quantities of PMCA1 and PMCA4 mRNA were not different in age-matched SHR
      vs. WKY rats, correlating with similar iCa2+ measurements. The expression of all
      three isoforms declined with age in SHR and WKY.

PMID- 9249595
TI  - Morphological heterogeneity of renal glomerular arterioles and distinct [Ca2+]i
      responses to ANG II.
AB  - The present study compares cytosolic calcium concentration ([Ca2+]i) responses to
      angiotensin II (ANG II) of afferent (AA) and efferent arterioles (EA) by taking
      account of the localization and morphological differences of EA. In outer cortex,
      1 nM ANG II induced smaller [Ca2+]i increases in thin EA than in AA[48 +/- 10 (n
      = 12) vs. 94 +/- 7 nM (n = 11); P < 0.001]. In inner cortex, two types of EA were
      considered, i.e., thin and muscular ones. The response to 1 nM ANG II was 35%
      lower in thin than in muscular EA (P < 0.05) but did not differ from that
      obtained with corresponding AA. In EA of the outer cortex, 1 microM nifedipine, a
      dihydropyridine blocker of voltage-operated channels (VOCC), did not affect
      calcium influx, which was suppressed by 1 mM NiCl2, a nonselective calcium entry
      blocker. In other arterioles, nifedipine inhibited by approximately 40% calcium
      entry, and remaining influx was blocked by NiCl2. These results indicate a
      relationship between the magnitude of [Ca2+]i responses, activation of
      dihydropyridine-sensitive VOCC by ANG II, and the muscular morphology in renal
      glomerular arterioles. They suggest that ANG II regulates differently local renal
      microcirculation. They do not, however, support the hypothesis of a greater
      sensitivity to ANG II of EA compared with the AA of a given nephron.

PMID- 9249597
TI  - The persistent effect of long-term enalapril on pressure natriuresis in
      spontaneously hypertensive rats.
AB  - Long-term angiotensin-converting enzyme inhibitor treatment has been shown to
      have a persistent antihypertensive effect in spontaneously hypertensive rats
      (SHR) long after discontinuation of treatment. To test the hypothesis that this
      persistent effect involves a shift in the pressure-natriuresis relation, we
      performed experiments in male, anesthetized SHR at 18 wk of age with fixed neural
      and hormonal influences on the kidney. Renal function was assessed at various
      levels of arterial pressure using standard clearance techniques. Enalapril (25
      mg.kg-1.day-1 in drinking water) was administered from 4 to 14 wk of age and
      again 3 days before renal function studies. The following four groups of SHR were
      studied: 1) 10-wk treatment, 2) 10-wk + 3-day treatment, 3) 3-day treatment, and
      4) untreated. Groups 1 and 4 had an intact renin-angiotensin system; groups 2 and
      3 had the renin-angiotensin system blocked. Mean arterial pressure (MAP, mmHg;
      means +/- SE) under Inactin anesthesia was 139 +/- 4 (n = 9), 109 +/- 3 (n = 8),
      149 +/- 1 (n = 9), and 181 +/- 7 mmHg (n = 9) for each of the four groups,
      respectively. Glomerular filtration rate was similar in all groups at resting
      levels of MAP, whereas renal blood flow was elevated in all treatment groups when
      compared with that in untreated SHR. Pressure-natriuresis, pressure-diuresis, and
      pressure-fractional sodium excretion curves for the 10-wk treatment group and 3
      day only treatment group were shifted leftward to significantly lower pressures
      by approximately 25 mmHg, compared with the untreated group. The curves for the
      treated +3-day group were shifted an additional 30 mmHg to the left. The
      relationship between renal artery pressure (RAP) and renal interstitial
      hydrostatic pressure was also shifted 25-30 mmHg but only in rats that received
      the long-term treatment with enalapril. Three-day enalapril had no significant
      effect on this relationship. These data indicate that the persistent effect of
      long-term enalapril treatment on arterial pressure in SHR is the result of a
      shift in the pressure-natriuresis relationship. The mechanism for this effect
      involves hemodynamic changes that act to improve transmission of RAP to the
      interstitium, resulting in enhanced sodium excretion for a given level of RAP.

PMID- 9249596
TI  - Calcitonin activates an Na(+)-independent HCO3(-)-dependent pathway in the rabbit
      distal convoluted tubule.
AB  - Calcitonin is known to stimulate Ca2+ reabsorption and natriuresis and to
      increase adenosine 3',5'-cyclic monophosphate levels in early distal tubule, but
      its effects on acid-base transport mechanisms are not well characterized in this
      segment. We found that recovery of cell pH (pH1) from an induced acid load (using
      NH4+) in single isolated segments of the initial portion ("bright") of the rabbit
      distal convoluted tubule (DCTb) was due to an ethylisopropylamiloride-sensitive
      Na+/H+ exchanger both in the absence and presence of HCO3-, but we found no
      evidence for participation of other mechanisms such as an H+ pump or an HCO3(-)
      dependent mechanism. Introduction of calcitonin stimulated an Na(+)-independent,
      HCO3(-)-dependent mechanism (0.17 +/- 0.04 pH units/min, n = 14) that
      reestablishes normal pHi after an induced acid load. This mechanism was observed
      only in the presence of CO2/HCO3- and was not inhibited by N-ethylmaleimide (1
      mM), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (200 microM), or Sch-28080
      nor stimulated by glutamine (2 mM) or ketoglutarate (0.5 mM), but it was
      dependent on chloride. We conclude that, in the DCTb, salmon calcitonin activates
      a latent Na(+)-independent, HCO3(-)-dependent mechanism.

PMID- 9249598
TI  - Phosphate transport in renal cell cultures of gy mice: evidence of a single
      defect in X-linked hypophosphatemia.
AB  - Although current theory holds that the murine homologs of X-linked
      hypophosphatemia represent mutations of two closely linked genes with distinct
      pathophysiological consequences, insufficient data are available to support this
      hypothesis. We investigated whether an intrinsic defect in renal sodium (Na+)
      dependent Pi cotransport truly distinguishes gy from hyp mice. We compared Pi
      transport in immortalized cells from S1 and S2 segments of the renal proximal
      convoluted tubule (PCT) of normal and gy mice. Cells from both murine models
      exhibit characteristics of differentiated PCT cells including gluconeogenesis,
      alkaline phosphatase activity, and parathyroid hormone (PTH)- and thyrocalcitonin
      (TCT)-dependent adenosine 3',5'-cyclic monophosphate production. More
      importantly, kinetic studies reveal that cells from the PCT of gy mice have
      intrinsically normal Pi transport and support the hypothesis that, as in hyp
      mice, a humoral abnormality is likely responsible for the renal Pi wasting in
      this mouse model. These observations are consistent with the conclusion that gy
      and hyp mice do not represent mutations of two closely linked genes but rather
      two separate mutations of the same gene.

PMID- 9249599
TI  - Osmo-mechanically sensitive phosphatidylinositol signaling regulates a Ca2+
      influx channel in renal epithelial cells.
AB  - Regulation of dihydropyridine (nifedipine)-sensitive calcium influx was studied
      in rabbit culture proximal tubule cells using the fura 2 fluorescence ratio
      technique. "Osmo-mechanically induced" swelling of cells by exposure to hypotonic
      medium (220 mosmol/kgH2O) caused a rapid rise in intracellular calcium that was
      predominantly due to influx of calcium via both dihydropyridine-sensitive
      (nifedipine-sensitive) and -insensitive calcium influx pathways. The
      dihydropyridine-sensitive pathway was regulated, in part, by the
      phosphatidylinositol signaling pathway. Inhibition of phospholipase C by
      treatment with 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), inhibition
      of protein kinase C (PKC) by staurosporine, or long-term (24 h) treatment with
      phorbol 12-myristate 13-acetate (PMA) to downregulate PKC abolished most of the
      osmo-induced, dihydropyridine-sensitive calcium influx signal. Short-term
      (seconds) PMA treatment to activate PKC produced a marked stimulation of both
      dihydropyridine-sensitive and -insensitive calcium influx in isotonic (2- to 3
      fold stimulation) and hypotonic (5-fold stimulation) conditions. In contrast,
      elevation of adenosine 3',5'-cyclic monophosphate (cAMP) by treatment with
      forskolin or inhibition of protein kinase A (PKA) by treatment with the cAMP
      analog, Rp-8-CPT-cAMPS (the Rp diastereoisomer of adenosine 3',5'-cyclic
      monophosphothionate), had little or no influence on calcium influx, including
      dihydropyridine-sensitive calcium influx. It is concluded that osmo-mechanical
      stress activates a dihyropyridine-sensitive calcium influx pathway that is
      predominantly regulated via the phosphatidylinositol signaling pathway and PKC
      and not through the cAMP/PKA signaling pathway.

PMID- 9249600
TI  - Specific coupling of a cation-sensing receptor to G protein alpha-subunits in
      MDCK cells.
AB  - Extracellular cations such as Ca2+ stimulate a G protein-coupled, cation-sensing
      receptor (CaR). We used microphysiometry to determine whether an extracellular
      cation-sensing mechanism exists in Madin-Darby canine kidney (MDCK) cells. The
      CaR agonists Ca2+ and Gd3+ caused cellular activation in a concentration
      dependent manner. mRNA for the CaR was identified by reverse transcription and
      polymerase chain reaction (PCR) using nested CaR-specific primers, identification
      of an appropriately located restriction site, and sequencing of the subcloned
      fragment obtained by PCR. G protein activation was evaluated using the GTP
      photoaffinity label [alpha-32P]GTP azidoanalide (AA-GTP). After stimulation with
      Gd3+ and cross-linking, plasma membranes were solubilized and immunoprecipitated
      with antisera specific for Gq/11 alpha and Gi alpha family members. Gd3+
      increased incorporation of AA-GTP into Gq/11 alpha precipitates by 146 +/- 48%
      and into G alpha i-2 and G alpha i-3 to a lesser extent but not into G alpha i-1.
      Direct effects of Gd3+ on the G proteins were ruled out using partially purified
      mammalian G proteins expressed in Escherichia coli or Sf9 cells. We conclude that
      MDCK cells possess a cell-surface CaR that activates Gq/11 alpha, G alpha i-2,
      and G alpha i-3 but not G alpha i-1.

PMID- 9249601
TI  - Cysteine S-conjugates activate transcription factor NF-kappa B in cultured renal
      epithelial cells.
AB  - Activation of NF-kappa B by the nephrotoxic and cytotoxic cysteine S-conjugate S
      (1,2-dichlorovinyl)-L-cysteine (DCVC) was investigated in porcine kidney-derived
      LLC-PK1 cells. DCVC induced binding of nuclear proteins to an NF-kappa B
      consensus oligonucleotide from the immunoglobulin kappa-light chain enhancer
      region, as determined by electrophoretic mobility shift assays, and the activated
      proteins were identified as the p50/RelA heterodimeric complex of NF-kappa B.
      Transient transfection experiments with a kappa B-controlled luciferase reporter
      construct showed that the NF-kappa B complex activated by DCVC was
      transcriptionally active. NF-kappa B transactivation was blocked by inhibition of
      DCVC bioactivation with the cysteine conjugate beta-lyase inhibitor
      (aminooxy)acetic acid, by the antioxidants N,N'-diphenyl-p-phenylenediamine and N
      acetyl-L-cysteine, and by the protein kinase inhibitor staurosporine. The
      cysteine S-conjugates S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine and S-(2
      chloro-1,1,2-trifluoroethyl)-L-cysteine also activated NF-kappa B in LLC-PK1
      cells. These results demonstrate that the NF-kappa B pathway is present in LLC
      PK1 cells and is induced by cysteine S-conjugates. Inhibition of DCVC-induced
      transactivation of NF-kappa B by staurosporine and by antioxidants indicate roles
      for protein kinases and oxidative stress in the NF-kappa B pathway.

PMID- 9249602
TI  - Role of renal nerves and endogenous dopamine in amino acid-induced glomerular
      hyperfiltration.
AB  - The present study was performed to clarify whether urinary dopamine excretion
      (UDAV) and renal nerves are involved in the increase in glomerular filtration
      rate (GFR) induced by amino acid (AA) infusion. In thiopental-anesthetized rats,
      L-phenylalanine-free solutions of 10 AA (10%) either with (AATyr, n = 10) or
      without (AA0, n = 10) L-tyrosine (0.5%) were infused. Compared with baseline
      values, AATyr increased GFR from 0.83 +/- 0.05 to 1.00 +/- 0.04 ml.min-1.100 g-1
      (P < 0.01) and UDAV almost fivefold from 5.81 +/- 0.46 to 28.1 +/- 7.4 pmol.min
      1.100 g-1 (P < 0.01). In contrast, infusion of AAo increased GFR as did AATyr but
      did not significantly change UDAV. The DA2-receptor antagonist S(-)-sulpiride
      dose-dependently (0.5 to 15 micrograms.min-1.100 g-1) inhibited the GFR response
      to AA infusion but did not affect UDAV. In rats that had undergone chronic
      bilateral renal denervation (DNX), the AA-induced hyperfiltration was abolished
      completely, regardless of whether L-tyrosine was present. DNX did not affect
      basal UDAV, but the increase in UDAV in response to AATyr was attenuated compared
      with rats with innervated kidneys. Renal sodium excretion was increased almost
      twofold due to AA infusion and did not correlate with UDAV significantly. The
      data suggest 1) that urinary dopamine does not play a significant role in the
      regulation of kidney function, 2) that renal innervation is essential in the GFR
      response to systemic AA infusion, and 3) that a dopaminergic mechanism apart from
      tubular dopamine excretion is involved as well.

PMID- 9249603
TI  - Podocyte alpha-actinin induction precedes foot process effacement in experimental
      nephrotic syndrome.
AB  - Attachment of podocytes to the glomerular basement membrane is thought to be
      mediated primarily by alpha 3/beta 1-integrins and by cytoskeletal proteins
      including actin, talin, vinculin, and alpha-actinin. We analyzed the expression
      of those molecules in rat glomeruli at several time points during induction of
      podocyte foot process effacement and nephrotic syndrome with puromycin
      aminonucleoside (PAN). PAN injection resulted in marked induction of glomerular
      alpha-actinin (40% increase vs. paired controls, P < 0.01), which clearly
      preceded development of podocyte foot process effacement and proteinuria and
      localized almost exclusively to podocytes. Delayed induction of glomerular alpha
      3-integrin (44% increase vs. paired controls, P < 0.01) following foot process
      effacement was also observed but was not restricted to podocytes. No significant
      changes in glomerular vinculin, talin, beta 1-integrin, or total actin expression
      occurred at any time point during disease development. We conclude that foot
      process effacement is preceded by induction of alpha-actinin in podocytes in
      experimental nephrotic syndrome. Altered expression of this actin cross-linking
      protein in podocytes may have a pathogenic role in foot process effacement in
      nephrotic syndrome.

PMID- 9249604
TI  - Modeling of progressive glomerular injury in humans with lupus nephritis.
AB  - We studied glomerular function longitudinally for 36-120 mo in 21 patients
      undergoing treatment for diffuse, proliferative lupus nephritis. We determined
      glomerular filtration rate (GFR) and glomerular oncotic pressure (IIGC) and
      computed the two-kidney ultrafiltration coefficient (Kf) at 6- to 12-mo
      intervals. The relationships and cross talk among the three variables over time
      were then analyzed by eigenfunction regression and canonical correlations. We
      also performed a morphometric analysis of serial biopsies and computed single
      nephron Kf in patent glomeruli at baseline and after 36-94 mo of follow-up.
      Patients were divisible into progressors (n = 12) or nonprogressors (n = 9)
      according to the presence or absence, respectively, of an irrevocable decline in
      GFR over time. Examination of longitudinal variables revealed GFR to be strongly
      related to Kf in all patients and inversely related to IIGC in progressors. By
      serial morphometric analysis we observed a threefold increase in the prevalence
      of global sclerosis in progressors but unchanged prevalence in nonprogressors.
      Whereas single-nephron Kf of remnant glomeruli increased to supernormal levels in
      nonprogressors, the absence of this compensatory phenomenon in progressors
      permitted GFR and Kf to decline in parallel with the declining number of
      functional glomeruli.

PMID- 9249605
TI  - Immunohistochemical localization of ANG II AT1 receptor in adult rat kidney using
      a monoclonal antibody.
AB  - Molecular and functional studies have suggested that AT1 receptors are present in
      most nephron segments, yet direct demonstration of AT1 at these sites is lacking.
      The present study was performed to determine the intrarenal localization of the
      AT1 receptor utilizing a monoclonal anti-peptide (amino acid residues 8-17)
      antibody (6313/G2) in adult male Sprague-Dawley rats. Western blot analysis of
      kidney protein extracts showed a predominant 41-kDa immunoreactive band
      corresponding to the molecular weight of the deduced cDNA sequence. To determine
      optimal fixation conditions, kidney tissues were immersion fixed in Bouin's
      solution, 10% buffered Formalin, or 4% paraformaldehyde. Specificity of
      immunostaining was documented by preadsorption of the antibody with the
      immunogenic peptide sequence. Prominent AT1 immunostaining was visualized in the
      proximal tubule brush-border and basolateral membranes. In addition, distal
      tubules, cortical and medullary collecting ducts, and the renal arterial
      vasculature exhibited specific immunoreactivity. Glomerular staining for AT1 was
      observed in mesangial cells and podocytes. Macula densa cells stained positively.
      Similar localization of the AT1 receptor was obtained using the three tissue
      fixation methods, although the intensity of vascular and glomerular staining was
      highest in Bouin-fixed tissues. The present study demonstrates that the AT1
      receptor is more widely distributed along the nephron than previously described
      and includes renal vascular smooth muscle and proximal and distal epithelial
      sites.

PMID- 9249606
TI  - A case presentation and review of neutropenic enterocolitis.
AB  - Neutropenic enterocolitis (NE) is an unusual complication of neutropenia. Its
      presentation is dramatic, treatment is controversial, and the outcome may be
      devastating. The available literature about this entity is mainly case reports
      and autopsy studies. We have recently performed a celiotomy on a patient who
      developed sepsis and an acute surgical abdomen three days following chemotherapy
      and radiotherapy for a metastatic adenocarcinoma with no known primary tumor. At
      surgery he was found to have a boggy right and recto-sigmoid colon with a grossly
      normal transverse colon. Intraoperative colonoscopy revealed mucosal ulceration
      and necrosis extending from the dentate line to the cecum. A total abdominal
      colectomy, closure of the rectal stump, and an ileostomy was performed.
      Postoperatively, the patient recovered from the abdominal septic process only to
      succumb to multiple system organ failure secondary to pulmonary sepsis. Upon
      review of the literature, we found 65 cases of NE that were suspected or
      diagnosed in the antemortem state and confirmed at surgery or autopsy. In this
      review, we intend to analyze these case reports, summarize the salient features
      of the disease and outline the optimal therapeutic approach.

PMID- 9249607
TI  - Management of ascites. A review.
AB  - Serum-ascites fluid albumin concentration gradient, ascites fluid
      polymorphonuclear cell count and ascites fluid cytology afford immediate
      diagnosis of the etiology of ascites. When cirrhotic patients with marked ascites
      do not respond to diuretics, abdominal paracentesis is the next step, if the
      ascites is severe enough to justify the risk. When all else fails over a period
      of several months, a peritoneovenous shunt may be appropriate. We have many
      options in the management of ascites now, but, in the future, the optimal therapy
      will include potent and nontoxic diuretic drugs and high-volume paracentesis.

PMID- 9249608
TI  - Etiology and prognosis of cryptogenic liver cirrhosis: possible contribution of
      hepatitis B virus.
AB  - Three female patients without type B or type C viral hepatitis, alcoholic,
      metabolic or autoimmune liver disease, were selected from 250 cases with
      histologically proven liver cirrhosis (M:F = 183:67). All three cases showed at
      least one positive aspect among three parameters of serum anti-HBc (RPHA, x1),
      HBV-DNA (gene S, nested PCR) and liver HBs and/or pre-S2 antigen
      (immunoperoxidase methods). Two cases may suggest a spontaneous disappearance of
      HBV from sera. Another case may suggest a contribution of mutant HBV which can
      not be detected by the routine tests. These HBV-related cirrhotic patients have
      done well clinically and have not been associated with hepatocellular carcinoma
      during the period from 6 to 12 years of follow-up when compared with 59.6% and
      65.4% prevalence of hepatocarcinogenesis in type B and type C hepatitis
      associated cirrhosis during the observation period of six and seven years on
      average, respectively.

PMID- 9249609
TI  - Two models of acute hepatic failure with extensive hepatic necrosis and blood
      ammonia elevation in small animals.
AB  - Acute hepatic failure models with extensive hepatic necrosis and hyperammonemia
      were developed in small animals. One model is bases on the retrograde infusion of
      ethanolamine oleate into the common bile duct of guinea pigs and another is based
      on the infusion of TNF-lipiodol emulsion into the portal tract of rats.

PMID- 9249610
TI  - Detection of SRY in a 46,XY female (Swyer's syndrome).
AB  - We describe sex reversal in a phenotypic female with 46,XY and SRY gene. Evidence
      accumulated here in the Swyer's syndrome may provide a better opportunity to
      study aberrations of gonadal development in man.

PMID- 9249611
TI  - Effects of repeated hyperthermal stress on blood cells in vivo.
AB  - The effects of repeated hyperthermal stress on blood cells were examined in seven
      healthy subjects who took three 3-minute 47 degrees C hotspring baths daily for
      three consecutive weeks. After a 3-minute 47 degrees C bath, the sublingual
      temperature was transiently increased about 1.8 degrees C, returning to the
      baseline level within 60 min. Two weeks after completing the 3-week bathing
      period, monocytes were increased and eosinophils were decreased significantly.
      Total lymphocytes and CD3+ cells tended to be decreased. Interestingly, CD4+
      cells were decreased significantly at the time of completing the 3-week bathing
      period and returned to the baseline level two weeks later. These findings suggest
      that repeated hyperthermal stress may induce alteration of the blood cells.

PMID- 9249612
TI  - Signal averaged electrocardiogram after exercise in patients with mitral valve
      prolapse.
AB  - While late potentials are correlated with an increased incidence of ventricular
      tachycardia, they are not necessarily a good predictor of ventricular electrical
      instability in patients with mitral valve prolapse (MVP). Our objective was to
      determine whether the signal averaged electrocardiogram (SAECG) after exercise
      can discriminate groups with a higher frequency of ventricular arrhythmia from
      those without. The SAECG was recorded before and after treadmill exercise in 20
      normal subjects (N group), 20 patients with MVP (MVP group) and 10 patients with
      old myocardial infarction (MI group). Five patients (25%) in the MVP group and
      two patients (33%) in the MI group had late potentials before exercise. Late
      potentials in the MI group did not disappear with exercise, whereas they
      disappeared with exercise in two patients in the MVP group. The results suggest
      that the late potentials observed in patients with MVP differ in nature from
      those with old myocardial infarction and are not always related to lethal
      arrhythmia.

PMID- 9249613
TI  - Participation of the pituitary-thyroid axis in the cardiovascular system in
      elderly patients with congestive heart failure.
AB  - The relationship between the pituitary-thyroid axis and the cardiovascular system
      in patients with congestive heart failure (CHF) remains unknown. Therefore, we
      attempted to determine serum levels of thyroid hormones in relation to plasma
      atrial natriuretic peptide (ANP) levels and left ventricular (LV) function in
      patients with CHF. The echocardiographic ejection fraction significantly
      correlated with the thyroid stimulating hormone (TSH) (p < 0.005) and free
      triiodothyronine (FT3)/free thyroxine (FT4) ratio (p < 0.005), respectively, in
      patients with CHF but not in control subjects. TSH was positively correlated with
      the FT3/FT4 ratio (p < 0.01) in CHF. In patients with CHF, TSH and thyroid
      hormones may participate in regulatory mechanisms of the cardiovascular system
      and altered thyroid hormone metabolism, which was characterized by a euthyroid
      sick syndrome.

PMID- 9249614
TI  - Transient sick sinus syndrome associated with immunoblastic lymphadenopathy.
AB  - We describe a very rare case of immunoblastic lymphadenopathy (IBL) accompanied
      with a sick sinus syndrome (SSS) in a 64-year-old male. SSS presented with
      progression of the IBL and subsided with improvement of the IBL following high
      dose prednisolone (PSL) therapy. The clinical course of this patient strongly
      suggested cardiac involvement in IBL and being the cause of the transient SSS. To
      our knowledge, this is the first case of IBL demonstrating SSS as a possible
      complication of the disease. This case may provide further information for the
      treatment of similar patients with IBL.

PMID- 9249615
TI  - Slime formation as a marker of serious infection with methicillin-resistant
      Staphylococcus aureus.
AB  - Strains of methicillin-resistant Staphylococcus aureus (MRSA) are potential
      pathogens in patients undergoing major surgery and in patients who are
      immunocompromised. Some MRSA produce a viscous extracellular slime that may
      interfere with immune function. In this study, slime formation by MRSA was
      examined in cases of nosocomial infection by this pathogen at a single hospital.
      The antibacterial resistance, phage and enterotoxin characteristics of strains
      isolated from patients with fatal infections were determined. MRSA strains were
      classified as those associated with fatal infection; causing progressive
      infection; causing superficial infection; and those isolated from the nasal
      cavity of the health-care professionals as a control group. The incidence of
      slime formation was highest in the MRSA associated with fatal infection. The
      incidence of slime formation in the control group was significantly lower than
      that in the other groups. Results suggest that slime formation by MRSA may be
      associated with a more severe infection. Rapid identification of slime-forming
      MRSA may facilitate the initiation of appropriate treatment and improve the
      patient's prognosis.

PMID- 9249616
TI  - Cytokine concentration in serum of lupus erythematosus patients: the effect on
      acute phase response.
AB  - In order to get a better insight into cytokine network regulation in systemic
      lupus erythematosus (SLE), we analyzed levels of interleukin-10 (IL-10),
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon
      gamma (IFN-gamma) in the sera from 36 SLE patients. Moreover, C-reactive protein
      (CRP), alpha-1-acid-glycoprotein (AGP), and alpha-1-antichymotripsin (ACT) serum
      levels were evaluated. Serum levels of IL-10 and IL-6 were significantly
      increased when compared with healthy controls. TNF-alpha and IFN-gamma did not
      differ from normal values. We established the relationship between IL-10 and IL-6
      as well as between IL-10 and TNF-alpha. None of the analyzed cytokines correlated
      with the acute phase protein levels. Based on the obtained data, we conclude that
      IL-10 may play the superior regulating role in SLE. A lack of correlation between
      the cytokines and acute phase proteins suggests their independence from cytokine
      regulation.

PMID- 9249618
TI  - Advances in the genetics of movement disorders: implications for molecular
      diagnosis.
AB  - Recent developments in molecular genetics have had a profound influence on the
      diagnosis and classification of inherited movement disorders. Huntington's
      disease is caused by the expansion of an unstable trinucleotide repeat sequence.
      Molecular diagnosis can now be performed by a simple PCR-based assay, and the
      study of the effects of the repeat expansion on the function of the encoded
      protein will allow to elucidate the molecular pathogenesis of the disease.
      Wilson's disease is caused by a large number of different mutations, which
      complicates molecular diagnosis. Genes for a number of inherited dystonic
      syndromes have been mapped, one of them, the gene for dopa-responsive dystonia,
      has already been identified. The genetic basis of several other prevalent
      movement disorders, such as essential tremor and the restless-legs syndrome
      however, is still obscure. Current research is also directed at the
      identification of inherited risk-factors in genetically complex movement
      disorders, such as Parkinson's disease.

PMID- 9249617
TI  - Curdlan sulfate (CRDS) in a 21-day intravenous tolerance study in human
      immunodeficiency virus (HIV) and cytomegalovirus (CMV) infected patients:
      indication of anti-CMV activity with low toxicity.
AB  - This study evaluated tolerance (and possible efficacy) for 21 days of i.v.
      administration at three dose levels of curdlan sulfate (CRDS) (a semisynthetic
      sulfated polysaccharide), administered over 30 minutes, in HIV and CMV (in some
      cases) infected individuals with CD4 levels < 500 cells/mm3. Half of the subjects
      were previously treated with reverse transcriptase inhibitors (RTI) (which were
      continued during the CRDS administration) and half the patients had no prior RTI
      treatment. Evaluation of other sulfated polysaccharides in HIV had been
      discontinued due to side effects and lack of activity. Three groups of HIV
      patients (also including subsets with CMV infection) were treated separately with
      50 mg/70 Kg, 100 mg/70 Kg and 200 mg/70 Kg of CRDS infused i.v. over thirty
      minutes daily for 21 days. In each dose group, half of the patients selected were
      being treated with a RTI and half were on no RTI. Patients were monitored for CD4
      cell levels, viral load in some cases, and safety parameters in blood. Samples of
      urine and semen were additionally taken for CMV by culture and for PCR assay in
      subsets of participants. CRDS in this 21 day study was well-tolerated and
      produced few reportable side effects. Systematic decreases in platelets and
      increases in p24 antigen previously seen with dextran sulfate were not observed
      in this study with CRDS. In the 21 patients testing positive for CMV at the start
      of the study, 12 were CMV negative at the end of 21 days. In an untreated
      historical control group, 0/36 went from CMV positive to negative over a period
      of 13-15 years. The anti-CMV activity of CRDS in this study, therefore, had a p
      value < 0.001, based on these historical controls. The marked temporary increases
      in CD4 levels seen in the single dose and the seven-day CRDS studies on HIV
      patients were also seen for 21 days in the current study (p = 0.0001). Treatment
      with CRDS seems promising against CMV in HIV infected patients, even with once
      daily dosing of this two-hour half-life drug. CRDS was well tolerated and its
      lack of toxicity makes it an attractive candidate for CMV-infected HIV patients.
      Multiple daily dosing, or the continuous infusion of CRDS, could lead to
      increased effectiveness against both HIV and CMV, especially in combination with
      other agents. Given the toxicity of existing anti-CMV agents, and considering the
      emerging importance of CMV in atherosclerotic disease, further studies on CRDS
      are warranted.

PMID- 9249619
TI  - A 99mTc-HMPAO single-photon emission computed tomography study of Lewy body
      disease.
AB  - The purpose of this study was to investigate patterns of 99mTc-HMPAO single
      photon emission computed tomography (SPECT) abnormality in Lewy body disease
      (LBD) and to compare findings with those encountered in Alzheimer's disease (AD).
      The study group comprised 20 consecutive patient referrals fulfilling clinical
      criteria for LBD. All patients had fluctuating cognitive impairment and
      'subcortical' dysfunction with or without perceptuospatial and/or linguistic
      impairment. Six patients had asymmetrical signs of parkinsonism (three left-sided
      and three right-sided), and 14 patients had symmetrical features of
      extrapyramidal involvement. 99mTc-HMPAO SPECT imaging was performed on LBD
      patients and findings compared with those of 57 patients with 'probable' AD and
      11 normal age-matched controls. Within the LBD and AD groups, patterns of
      cortical and subcortical blood-flow abnormality were compared with patterns of
      cognitive and neurological breakdown. LBD was associated with bilateral posterior
      cortical blood flow abnormality, a pattern strikingly similar to that found in
      AD. Within the LBD group, cortical blood-flow abnormality was found to reflect
      patterns of neurological dysfunction (parkinsonism) indicative of subcortical
      involvement. In contrast, cortical blood-flow changes did not reflect patterns of
      neuropsychological impairment suggestive of cortical dysfunction. Within the AD
      group, cortical blood-flow changes were mirrored by the pattern of
      neuropsychological impairment. Findings support the notion that cortical blood
      flow abnormality in LBD might reflect a combination of direct cortical pathology
      and cortical deafferentation secondary to subcortical Lewy body pathology. It
      would appear that 99mTc-HMPAO SPECT imaging is of limited value in the clinical
      differentiation of LBD and AD.

PMID- 9249620
TI  - Fatty acid dietary intake and the risk of ischaemic stroke: a multicentre case
      control study. UFA Study Group.
AB  - A low dietary intake of unsaturated fatty acids has been found in male patients
      with stroke as compared with controls in Italy, and a high consumption of meat
      has been associated with an increased risk of stroke in Australia. We present a
      case-control study, comparing the unsaturated and saturated fatty acids content
      of red cell membranes (which reflects the dietary intake of saturated and
      unsaturated fats) in 89 patients with ischaemic stroke and 89 controls matched
      for age and sex. In univariate analysis, besides hypertension, atrial
      fibrillation, ischaemic changes in ECG and hypercholesterolaemia, stroke patients
      showed a lower level of oleic acid (P = 0.000), but a higher level of
      eicosatrienoic acid (P = 0.009). Conditional logistic regression (dependent
      variable; being a case) showed that the best model included atrial fibrillation,
      hypertension, oleic acid and eicosatrienoic acids. These results confirm a
      possible protective role of unsaturated fatty acids against vascular diseases;
      however, we did not find any difference in the content of omega3 acids, which
      have been considered in the past to protect against coronary heart disease. We
      conclude that the preceding diet of patients with ischaemic stroke may be poor in
      unsaturated fatty acids (namely, oleic acid), and this defect is independent of
      other vascular risk factors. Only further studies will show whether changes in
      diet and/or supplement of unsaturated fatty acids might reduce the incidence of
      ischaemic stroke.

PMID- 9249621
TI  - Epilepsy patients: health status and medical consumption.
AB  - OBJECTIVE: To study the health status and medical consumption of outpatients with
      active epilepsy in comparison with the general population. DESIGN: Descriptive
      population study (multi-stage random sample). SETTING: Structured questionnaire.
      PATIENTS: Thirty-nine epilepsy patients compared with a general population of
      12,975. RESULTS: Epilepsy patients revealed poorer health, a higher mean
      complaint score (5.3 versus 3.7, P < 0.05), a higher score on the General Health
      Questionnaire (P < 0.05), a somewhat higher score on the bio-logical problem list
      (BIOPRO) (1.8 versus 1.4, P > 0.05), less active sports engagement (16% versus
      39%, P < 0.01), more fatigue (46 vs 29%, P < 0.05), dizziness (33 vs 10%, P <
      0.01), nervousness (28 vs 18%, P > 0.05), sleep disturbance (23 vs 15%, P > 0.05)
      and excitability (33 vs 15%, P < 0.01) when compared with the general population.
      The BIOPRO showed problems in epilepsy patients on specific items related to self
      confidence (P < 0.001) Epileptic patients do not show more absence due to
      illness, from work, school or at home (15 vs 18%, P > 0.05) and/or more problems
      at work or in the family when compared with the general population. Almost half
      of epilepsy patients had consulted a specialist in the past 2 months (46 vs 23%
      of the general population, P < 0.001). Epilepsy patients consulted the family
      physician slightly more often than other responders (3.0 versus 2.3, P > 0.05)
      and contacted the family physician's assistant considerably more often (2.3
      versus 0.7, P < 0.001). One-third of epilepsy patients consulted an alternative
      healer in the past 5 years versus 14% in the general population (P < 0.001).
      CONCLUSIONS: The study shows an excess of psychosocial problems and medical
      consumption in epilepsy patients, but not more absence from work or problems at
      work or in the family. Further development of a quality of life instrument
      specific to epilepsy is advised.

PMID- 9249622
TI  - A study of visual hallucinations in patients with Parkinson's disease.
AB  - In a hospital-based case-control study 29 patients with idiopathic Parkinson's
      disease (PD) and visual hallucinations (VH) were compared with 58 PD patients
      matched for age and disease duration, but without VH. VH patients had more
      frequently sleep disturbances and dementia, higher PD-related disability (Schwab
      England scale), and took selegiline more frequently as an anti-Parkinsonian drug.
      The patient groups did not differ in age at PD onset, Webster score, treatment
      duration, dosage of any anti-Parkinsonian drug, frequency of levodopa-associated
      movement disorders, or measures on brain CT. After a median follow-up period of
      27 months more VH patients had developed wearing-off and freezing phenomena,
      while their scores in the Mini Mental State Examination were lower. Nursing home
      placement during the follow-up period was associated with higher PD-related
      disability in VH patients.

PMID- 9249623
TI  - Gilles de la Tourette's syndrome in special education schools: a United Kingdom
      study.
AB  - In order to determine the prevalence of tic disorders in children with severe
      school problems requiring a residential facility and comparison groups of
      children in regular day schools, we performed direct clinical examinations for
      the presence of tics and Gilles de la Tourette's syndrome (GTS) in 20 children
      from a residential school for emotional and behavioral difficulties (EBD); 25
      children from a residential school for learning disabilities; 17 "problem"
      children (PC) (identified by teachers as having academic or behaviour problems)
      and 19 normal children (NC) selected at random (using random numbers) from a
      regular school. Of the EBD students, 65% were judged to have definite tics as
      compared with 24% of students with learning difficulties (P < 0.05), 6% of PC (P
      < 0.003) and none of the NC (P < 0.0006) group. Most of the affected students met
      diagnostic criteria for GTS. Our findings suggest that GTS is commonly associated
      with the need for special education and that this association is particularly
      robust for children with severe school problems. In these children, the presence
      of tics may be an indicator of an underlying dysfunction of neurological
      development.

PMID- 9249624
TI  - Early asymmetric neuropathy in primary Sjogren's syndrome.
AB  - We report three female patients, 43, 47, and 50 years old, with a rare asymmetric
      form of clinically pure sensory neuropathy associated with primary Sjogren's
      syndrome. In all three patients glandular involvement was accompanied by
      peripheral nerve disease. Sensory conduction studies showed completely normal
      results in two of three patients. Yet assessment of thermal-specific thresholds
      and thermal pain thresholds, combined with autonomic function tests (sympathetic
      skin response and R-R interval variation) supported the clinical suspicion of
      peripheral nerve disorder. Sjogren's syndrome must be considered in asymmetric
      sensory neuropathies of unknown cause.

PMID- 9249625
TI  - Frequency and clinical correlates of vitiligo in myasthenia gravis.

PMID- 9249626
TI  - Paroxysmal hemiballism and idiopathic hypoparathyroidism.

PMID- 9249628
TI  - An atypical case of partial merosin deficiency congenital muscular dystrophy.

PMID- 9249627
TI  - Intronic GAA triplet repeat expansion in Friedreich's ataxia presenting with pure
      sensory ataxia.

PMID- 9249629
TI  - Paroxysmal choreoathetosis--a disorder related to Huntington's disease?

PMID- 9249630
TI  - Pyomyositis and osteomyelitis in a patient with radiating pain in the leg.

PMID- 9249631
TI  - Effects of combined topical metronidazole and mechanical treatment on the
      subgingival flora in deep periodontal pockets in cuspids and bicuspids.
AB  - The Effect on the subgingival microflora of a single topical administration of a
      95% collagen and 5% metronidazole device in combination with debridement was
      investigated in 30 adult periodontitis patients in comparison with mechanical
      treatment alone. For each patient, plaque samples from test and control sites in
      cuspids and bicuspids were collected for culture and enumeration of total
      anaerobically cultivable bacteria (TA), black-pigmented anaerobes (BPA), and
      Actinobacillus actinomycetemcomitans (Aa). Spirochetes and fusiforms were
      quantified by direct microscopic examination after Giemsa staining. A decrease
      was observed for all parameters, and a significant difference in comparison with
      the control group was found for fusiforms. After treatment, a lower number of Aa
      positive sites were observed in the test group (13/25). These results show that a
      single application of topical metronidazole seems to be effective as adjunctive
      antimicrobial treatment in adult periodontitis.

PMID- 9249632
TI  - Relationship between serum antibody levels and subgingival colonization of
      Porphyromonas gingivalis in patients with various types of periodontitis.
AB  - Porphyromonas gingivalis is considered to be an important pathogen in
      periodontitis. The present study investigates the relationship between serum anti
      P. gingivalis IgG antibody levels and the subgingival distribution of P.
      gingivalis in patients with periodontitis. We examined subgingival plaque samples
      from 15 patients with adult periodontitis (AP), 8 patients with early-onset
      periodontitis (EOP), and 6 clinically healthy individuals. The samples were
      collected from periodontal pockets or gingival crevices of all remaining teeth in
      each subject. The total number of samples was 3,024, ranging from 76 to 120 per
      subject. Probing depth and bleeding at each sample site were recorded. P.
      gingivalis was detected using a non-radioactive whole genomic DNA probe. Serum
      samples were taken from the subjects, and the serum anti-P. gingivalis IgG
      antibody titer was determined by enzyme-linked immunosorbent assay (ELISA). P.
      gingivalis was recovered from all AP and EOP patients, and from 3 of the 6
      healthy subjects. Two significant positive correlations were observed among the
      subjects. The serum anti-P. gingivalis IgG antibody titer correlated with
      detection frequency of P. gingivalis, and the antibody titer correlated with the
      amount of P. gingivalis detected. Higher levels of P. gingivalis were detected in
      the EOP group than in the AP group. However, no significant difference was found
      in the serum IgG titer levels between EOP and AP patients. These findings suggest
      a direct relationship between the serum anti-P. gingivalis IgG levels and
      subgingival P. gingivalis colonization; however, the functional capabilities of
      IgG antibodies may vary among the various types of periodontitis patients.

PMID- 9249633
TI  - The relationship between gingivitis and the serum antibodies to the microbiota
      associated with periodontal disease in children with Down's syndrome.
AB  - Gingival inflammation in Down's syndrome children (DS) develops earlier and is
      more rapid and extensive than in non-DS children. Abnormalities in host response
      to the oral flora have been proposed as etiological factors of this gingival
      inflammation. However, the relationship between gingivitis and the host response
      to oral microorganisms in DS by age has not been determined. The objective of
      this study was to clarify this relationship. Sera were obtained from 75 DS
      subjects (aged 2 to 18 years) and their gingival health assessed using a modified
      PMA Index (M-PMA). Antibody titers to Porphyromonas gingivalis (Pg), Prevotella
      intermedia (Pi), Treponema denticola (Td), Fusobacterium nucleatum (Fn),
      Selenomonas sputigena (Sel), Actinobacillus actinomycetemcomitans (Aa), and
      Streptococcus mitis (Mi) were determined using the micro-ELISA. DS subjects under
      4 years old were found to have significantly more gingival inflammation than did
      normal children the same age. A significant positive correlation (r = 0.548, P <
      0.0001) existed in the relationship between M-PMA score and plaque score for
      subjects in the G1 age group (deciduous dentition). At G1, the average antibody
      titers to Aa, Mi, and Fn exceeded those of the normal adult reference serum pool.
      In addition, IgG antibody titers to Pg, Aa, Fn, Sel, and Mi correlated
      significantly with the M-PMA scores in the G1 age group. There was a correlation
      between age (2 to 18 years) and these antibody titers. IgG antibody titers to Pg,
      Aa, Sel, and Mi increased significantly with increasing M-PMA score. Furthermore,
      the IgG antibody titers to Pg were higher (P < 0.05) in the most extensive
      disease group compared to the DS no-disease group. The IgG antibody titers to Pg
      at G3 (early puberty) were significantly higher when compared to G1 (preschool
      children). The IgM antibody titers to Aa at G3 were higher (P < 0.05) when
      compared to G1. This study suggests that colonization by Aa and Fn are closely
      associated with the onset of gingival inflammation in DS patients under 5 years
      old. Colonization by Pg, Aa, Sel, and Mi in DS appears to be associated with
      gingivitis at puberty.

PMID- 9249634
TI  - Root planing following short-term pocket distention.
AB  - This study evaluated the effectiveness of root planing following short-term
      pocket distention. Seventy-five single-rooted teeth with probing depths > or = 5
      mm and < or = 10 mm were selected. The teeth were randomly divided into three
      treatment groups. In groups 1 and 2 a gingival retraction cord (aluminum sulfate
      impregnated in group 1 and non-impregnated cord in group 2) was packed
      subgingivally for 30 minutes. Following removal of the cord, the teeth were
      scaled and root planed. In group 3 the teeth were root planed only. Following
      instrumentation, the teeth were extracted and examined under a stereomicroscope.
      The residual calculus on the root surface of each tooth was measured using a
      computerized image analysis system. The quantities were compared using a two-way
      ANOVA and Chi-square test. The results showed that 46.3% of all root surfaces had
      detectable residual calculus and that the mean percentage of residual calculus
      per root surface was 4.41% following root planing. Forty percent of the root
      surfaces in group 1 had residual calculus, 38.0% in group 2, and 61.0% in group
      3. There was a statistically significant difference (P < 0.01) between groups 1
      and 2 compared to group 3. The mean calculus per root surface for groups 1, 2,
      and 3 was 3.03%, 3.04%, and 7.15%, respectively. Significant differences (P <
      0.005) were found between groups 1 and 2 compared to group 3. These results
      indicate that subgingival calculus removal in deep pockets is enhanced with short
      term pocket distention, and that there is no added benefit to having aluminum
      sulfate present in the retraction cord.

PMID- 9249635
TI  - Evidence for healing of class II and III furcations after GTR therapy: digital
      subtraction and clinical measurements.
AB  - In 21 patients with advanced periodontitis, 39 teeth exhibiting class II (n = 21)
      and class III (n = 18) furcations were treated by the guided tissue regeneration
      technique using expanded polytetrafluoroethylene (ePTFE) membranes (n = 20) or
      bioabsorbable barriers (n = 19), respectively. Clinical parameters were assessed
      before and 6 months after surgery. Presurgically and 6 months postsurgically, 35
      pairs of standardized bitewing radiographs were taken. Using subtraction
      radiography, gain of bone density within furcation areas was assessed. Eighteen
      radiographs showed sufficiently accurate geometry to be analyzed by subtraction.
      Within the defects suitable for subtraction, the average gain of vertical
      attachment assessed was 1.35 +/- 1.27 mm in the class II furcation group and 1.58
      +/- 1.37 mm in the class III furcation group. The average horizontal attachment
      gain in the class II furcation group was 1.96 +/- 0.59 mm. No statistically
      significant differences were observed between results after GTR therapy using non
      resorbable and bioabsorbable barriers. Radiographic bone gain as assessed by
      subtraction analysis correlated with vertical (r = 0.458, P < 0.025) and
      horizontal (r = 0.734, P < 0.005) attachment gain. A statistically significant
      number of more radiographs for maxillary molars were not suitable for subtraction
      analysis than mandibular molars (P < 0.05). Further, statistically more
      radiographs that were taken with potentially unstable support of the filmholder
      were not suitable for subtraction analysis than those with stable support (P <
      0.05). There is a statistically significant correlation between clinical
      improvements and bony fill within furcation defects. Only 18 of 35 pairs of
      radiographs were suitable for subtraction analysis. Subtraction analysis of
      maxillary molars seems to be more difficult than assessment of radiographic bone
      changes in mandibular molars. Potentially stable support of the filmholder seems
      to be a condition to provide radiographs suitable for subtraction analysis.

PMID- 9249636
TI  - Regression of nifedipine-induced gingival hyperplasia following switch to a same
      class calcium channel blocker, isradipine.
AB  - Patients with nifedipine-induced gingival hyperplasia (GH) often require
      continued calcium channel blocker therapy. Switches to diltiazem and verapamil
      have been described; however, these drugs are of a different chemical class and
      present therapeutic limitations in some patients. The purpose of this study was
      to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine
      derivative with a low incidence of GH. Fourteen patients with nifedipine-induced
      GH were given a medical exam and a periodontal exam. The following parameters
      were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT),
      plaque index (PI), and gingival index (GI). Intraoral photographs, study models,
      and a gingival biopsy for histological examination were taken. Following baseline
      measures, patients were randomized to continued treatment with nifedipine or an
      equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal
      parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected
      to receive 4 weeks of open label isradipine therapy, with biweekly examination
      continuing through the open label phase. The isradipine treatment arm showed a
      mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter
      (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the
      alternate treatment arm. Clinically, 60% of patients treated with isradipine
      exhibited a decrease in hyperplasia, while 66% of patients treated with
      nifedipine demonstrated an increase in hyperplasia, a significant difference (P <
      0.05). When combined with open label data, patients switching therapy to
      isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from
      baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an
      increase in gingival overgrowth. All patients exhibited adequate control of
      hypertension. We conclude that in hypertensive patients with nifedipine-induced
      GH, switching hypertensive therapy to isradipine may result in a regression of
      GH. When coupled with aggressive oral hygiene treatment, this drug may provide a
      reasonable option for patients requiring dihydropyridine treatment.

PMID- 9249637
TI  - Subgingival microbiota in adult Chinese: prevalence and relation to periodontal
      disease progression.
AB  - The "checkerboard" Dna-Dna hybridization technology was used to study the
      epidemiology of 18 microbial species associated with various states of
      periodontal health and disease, in a sample of 148 Chinese subjects never exposed
      to systematic dental therapeutic intervention, aged 30 to 39 and 50 to 59 years.
      Our aims were to: 1) describe the prevalence of these microorganisms; 2)
      correlate the microbiological and clinical profiles of the subjects; and 3)
      examine the association between the microbiological variables and the
      longitudinal changes of periodontal status that occurred over a preceding 10-year
      period. A maximum of 14 subgingival samples were obtained from each subject-1,864
      in all. The frequency of occurrence of the 18 species examined was high in this
      Chinese population, on both the subject and the tooth site level. However, all
      species were not found equally capable of reaching high numbers in the
      subgingival samples and, as a rule, colonized heavily only limited proportions of
      tooth sites within each mouth. There was a profound increase of certain species
      such as Porphyromonas gingivalis, Treponema denticola, and Bacteroides forsythus
      in deep pockets or progressing sites. Multivariate techniques using the
      subgingival profile could effectively discriminate between deep/shallow pockets
      and progressing/ stable tooth sites. The microbiological variables showed an
      enhanced discriminating potential when classifications were performed on the
      individual subject level. Colonization by P. gingivalis, B. forsythus,
      Campylobacter rectus, and T. denticola at levels exceeding certain thresholds
      entailed a significantly increased probability (odds ratios > 4) for an
      individual subject to harbor deep pockets or progressing tooth sites.

PMID- 9249638
TI  - Comparison of a bioabsorbable GTR barrier to a non-absorbable barrier in treating
      human class II furcation defects. A multi-center parallel design randomized
      single-blind trial.
AB  - This multi-center single-blind study compared clinical outcomes following guided
      tissue regeneration (GTR) treating human Class II furcation defects with a new
      polylactic-acid-based bioabsorbable barrier (test treatment) or a non-absorbable
      ePTFE barrier (control treatment). Clinical parameters evaluated were change in
      vertical attachment level (VAL), horizontal attachment level (HAL), probing depth
      (PD), and gingival margin location (REC). Surgical treatment resulted in
      clinically and statistically equivalent changes when comparisons were made
      between test and control treatments. VAL gain was 2.0 mm for test and 1.6 mm for
      control groups; HAL gain was 2.1 mm for both test and control groups. PD
      reduction was 2.3 mm for the test group and 2.1 mm for the control group. Test
      sites experienced an additional 0.3 mm of recession beyond baseline; control
      sites, 0.5 mm. Within-group comparisons showed that the amount of recession was
      not significantly different from baseline in the test group. Recession in the
      control group was significantly different from baseline. All other parameters in
      both the test and control groups were significantly different from baseline.
      Evaluation of safety data indicated no significant differences between test and
      control treatments, although there was a strong trend for the control group to
      have more postoperative abscess or suppuration than test sites (control = 11;
      test = 4; P = 0.06).

PMID- 9249639
TI  - Prevalence of amlodipine-related gingival hyperplasia.
AB  - Calcium channel blockers are known to contribute to gingival hyperplasia. The
      vast majority of reports discuss patients taking the drug nifedipine. During the
      past few years a newer calcium channel blocker, amlodipine, has been used with
      increasing frequency. To date, six cases have been published indicating that
      amlodipine may also promote gingival hyperplasia; however, no data have been
      reported regarding the prevalence of this phenomenon. The purpose of this study
      was to examine a large group of patients taking amlodipine and determine the
      prevalence of gingival hyperplasia. One hundred fifty dentate patients who had
      been taking amlodipine, 5 mg per day for at least 6 months, volunteered to
      undergo a screening examination for gingival hyperplasia. Mild hyperplasia (< 1/3
      clinical crown) was found in five patients-a prevalence of 3.3%. This is
      significantly less (P < .001) than rates reported for patients taking nifedipine,
      and not significantly different from rates previously reported in control groups
      of cardiac patients not taking calcium channel blockers. The results from this
      group of patients indicated that amlodipine, 5 mg per day, did not induce
      gingival hyperplasia.

PMID- 9249640
TI  - Comparison of bioabsorbable laminar bone membrane and non-resorbable ePTFE
      membrane in mandibular furcations.
AB  - The purpose of the study was to compare clinical parameter changes and osseous
      regeneration in 12 pairs of comparable Class II mandibular molar furcation
      invasion defects using either a bioabsorbable demineralized laminar bone
      allograft membrane or a non-resorbable expanded polytetrafluoroethylene (ePTFE)
      membrane as a barrier in guided tissue regeneration. Measurements with calibrated
      periodontal probes were made to determine soft tissue recession, probing depth,
      and attachment levels. Defects within each pair were randomly selected for
      treatment with either bioabsorbable demineralized bone allograft membrane or
      ePTFE membrane. All defects were concurrently grafted with particulate
      demineralized freeze-dried bone allograft (DFDBA). Additional measurements were
      made at surgery to determine crestal resorption and the vertical and horizontal
      dimensions of the osseous defects. The temporal course and extent of membrane
      exposures were also recorded. The non-resorbable membrane was retrieved 6 weeks
      following placement. Six months following initial surgical treatment, each site
      was surgically re-entered and all soft and hard tissue measurements repeated.
      Descriptive statistical analysis revealed that both treatments resulted in
      significant within-group mean vertical and horizontal osseous fill, but no
      statistical difference emerged between the groups. As based on this pilot study,
      laminar bone membrane may be as effective as ePTFE when used in conjunction with
      DFDBA for treatment of Class II mandibular molar furcation bone defects. This
      pilot study of low power suggests that these two materials may be equivalent when
      used in conjunction with DFDBA. Further studies of much higher power and of the
      laminar bone alone as compared to positive and negative controls are required.
      Laminar bone does not require a secondary surgical procedure for removal and may
      undergo less frequent instances and degrees of exposure during healing.

PMID- 9249641
TI  - Cervical enamel projection and intermediate bifurcational ridge correlated with
      molar furcation involvements.
AB  - In this study, we investigated the cervical enamel projection (CEP) and
      intermediate bifurcational ridge (IBR) correlated with localized molar furcation
      involvement (FI). Study samples consisting of 87 hopeless permanent mandibulars
      (56 first and 31 second molars), which required extraction for periodontal
      therapy, were randomly collected from the School's Dental Clinic. The furcal
      defects, CEPs, and IBRs of molars were diagnosed via clinical probing, periapical
      radiographs, and inspection of ground tooth sections of extracted teeth with a
      stereomicroscope. Prevalence and distribution of molars with CEPs and/or IBRs
      were also analyzed. Probing depths (PD), clinical attachment loss (CAL), gingival
      index (GI), and plaque index (PLI) were measured for the buccal and lingual
      surfaces of molar furcal areas. Moreover, the relationships between the molar FI
      with and without CEPs and IBRs and periodontal status were analyzed using
      Student's paired t-test. Based on those results, we can conclude the following:
      1) among 87 molars with FIs examined, 63.2% (55/87) had cervical enamel
      projections and bifurcational ridges, and the prevalence was greatest in
      mandibular first (67.9%, 38/56) and second (54.8%, 17/31) molars; and 2) the
      differences in mean PD, CAL, PLI, and GI between the molars with and without CEPs
      and IBRs were highly significant (P < 0.001) in the mandibular first and second
      molars.

PMID- 9249642
TI  - Histologic aspects of the bone and soft tissues surrounding three titanium non
      submerged plasma-sprayed implants retrieved at autopsy: a case report.
AB  - The authors report the histological features found around three non-submerged
      titanium plasma-sprayed implants retrieved, after a 10-month loading period, from
      an autopsy case. At the time of implant insertion, the clinician had noted a wide
      vestibular dehiscence of the central implant, and it was decided to use a
      bioabsorbable membrane for guided bone regeneration in this area. After specimen
      processing, it was possible at low magnification to observe that in the most
      vestibular slides, the central implant was almost completely surrounded by
      connective tissue, while in the most lingual slides, the quantity of bone around
      the implant tended to increase. The other two implants had a bone-implant contact
      percentage of about 60%. Only in a few areas was mineralized bone in direct
      contact with the metal surface, while around the major portion of the implant
      perimeter a layer of unmineralized, red-stained, osteoid material was present. No
      inflammatory infiltrate was present in the epithelium and in the supracrestal
      connective tissues. The fibers of this tissue had a different orientation: in the
      most coronal portion of the implants (smooth surface), they tended to run
      parallel implant's surface, while in the most apical region (plasma-sprayed
      surface), they tended to be arranged in a perpendicular fashion. These results,
      in man, were strikingly similar to those previously reported in dogs and monkeys.

PMID- 9249643
TI  - Cells with osteoblastic phenotypes can be explanted from human gingiva and
      periodontal ligament.
AB  - Considerable phenotypic heterogeneity has been reported in gingival fibroblasts.
      Similarly, cells from the periodontal ligament (PDL) can be isolated with
      different phenotypes. Although it has been suggested that cells from the gingiva
      do not contribute to the formation of hard tissue, it is theoretically possible
      that under appropriate stimuli, immature mesenchymal cells in gingiva could
      differentiate along an osteoblastic pathway. Differentiation of immature
      mesenchymal cells into osteoblasts following stimulation with osteoinductive
      factors has been demonstrated in muscle. We undertook experiments to establish
      whether cells with osteoblastic characteristics could be identified from human
      gingiva as well as from human periodontal ligament. Some cell populations from
      each of these tissues were found to have high basal alkaline phosphatase
      activity, to release osteocalcin in response to 1,25(OH)2 VitD3, and to form a
      mineralized matrix. Thus, cells can be isolated from the gingiva and PDL that
      exhibit phenotypic markers, which taken together are characteristic of
      osteoblastic cells. Other cell populations derived from the PDL and gingival
      connective tissue were isolated that had fibroblastic characteristics. These
      studies support the concept that gingival tissue can give rise to cells which may
      differentiate along either a fibroblastic or an osteoblastic pathway.

PMID- 9249644
TI  - The discovery and function of COX-2.

PMID- 9249645
TI  - Outcome of specific COX-2 inhibition in rheumatoid arthritis.
AB  - We reviewed data suggesting the hypothesis that specific inhibition of the
      inducible isoform of cyclooxygenase, COX-2, would provide therapeutic benefit in
      patients with rheumatoid arthritis (RA) with less gastrointestinal toxicity and
      presented the results of a therapeutic trial to test this hypothesis. Various
      doses of the selective COX-2 inhibitor, celecoxib, or placebo were used to treat
      patients with RA in a 4 week, double blind, placebo controlled trial. Celecoxib
      provided significant improvement in patient global assessment, morning stiffness,
      and the number of painful and tender joints compared with placebo. In addition,
      the number of withdrawals in celecoxib treated patients was significantly less
      than in the placebo group. No significant adverse events and no difference in the
      total number of adverse events were noted between the placebo and celecoxib
      groups. At the doses employed, celecoxib inhibited only COX-2 and not COX-1.
      Specific COX-2 inhibition with celecoxib causes significant improvement in the
      signs and symptoms of RA.

PMID- 9249646
TI  - COX-1 and COX-2 tissue expression: implications and predictions.
AB  - It has been proposed that cyclooxygenase (COX)-1 and COX-2 subserve different
      physiologic functions largely because of the striking differences in their tissue
      expression and regulation. COX-1 displays the characteristics of a "housekeeping"
      gene and is constitutively expressed in almost all tissues. COX-1 appears to be
      responsible for the production of prostaglandins (PG) that are important for
      homeostatic functions, such as maintaining the integrity of the gastric mucosa,
      mediating normal platelet function, and regulating renal blood flow. In sharp
      contrast, COX-2 is the product of an "immediate-early" gene that is rapidly
      inducible and tightly regulated. Under basal conditions, COX-2 expression is
      highly restricted; however, COX-2 is dramatically upregulated during
      inflammation. For example, synovial tissues in patients with rheumatoid arthritis
      (RA) express increased levels of COX-2. In animal models of inflammatory
      arthritis, COX-2 increases in parallel with PG production and clinical
      inflammation. In vitro experiments have revealed increased COX-2 expression after
      stimulation with proinflammatory cytokines, such as interleukin 1 (IL-1) and
      tumor necrosis factor-alpha (TNF-alpha), in many cell types, including
      synoviocytes, endothelial cells, chondrocytes, osteoblasts, and
      monocytes/macrophages. Another distinguishing characteristic of COX-2 is
      decreased expression in response to glucocorticoids. COX-2 is also increased in
      some types of human cancers, particularly colon cancer. Mechanisms underlying the
      association between COX-2 overexpression and tumorigenic potential may include
      resistance to apoptosis, or programmed cell death. Upregulated COX-2 expression
      undoubtedly plays a role in pathologic processes characterized by increased local
      PG production. One would predict, based on current information regarding the
      differential tissue expression of COX-1 and COX-2, that highly selective
      inhibitors of COX-2 will provide effective antiinflammatory activity with marked
      reduction in toxicity.

PMID- 9249648
TI  - Intraspecific variation in key morphological characters of Culiseta melanura
      (Diptera:Culicidae).
AB  - Culiseta melanura (Coq.), the enzootic vector of eastern equine encephalitis in
      North America, is polymorphic for a trait used as a key diagnostic character. The
      absence of white abdominal bands distinguishes this species in several prominent
      keys to North American mosquitoes. However, this is an environmentally induced,
      nongenetic trait that cannot be used as a key character for diagnosing Cs.
      melanura. In light trap collections, banded specimens occur in early spring and
      summer, and nonbanded adults appear in late summer-autumn. Larvae reared in
      laboratory conditions produce nonbanded adults. Progeny reared from banded
      mothers are uniformly nonbanded. Biochemical genetic results indicate that
      banding is not correlated with a distinctive genotype or presence of cryptic
      species. In 18 enzyme loci screened, neither diagnostic alleles nor large
      differences in allele frequencies were detected between field-collected
      representatives of the two forms. Genetic variability was relatively low in the
      28-year-old laboratory colony (average heterozygosity = 7%; average number of
      alleles per locus = 1.4), whereas in field samples, the variability was typical
      of field populations (average heterozygosity = 12-19%; average number of alleles
      per locus = 1.6-1.8), with the presence of both polymorphic and private alleles.
      The population genetic profile and comparisons among geographically distinct
      populations represent the first such presentation for any species in the genus
      Culiseta.

PMID- 9249647
TI  - Pain management in osteoarthritis: the role of COX-2 inhibitors.
AB  - Pain is the major symptom that leads patients to consult their physicians for the
      treatment of arthritis; therefore, effective pain control is an important goal in
      the management of this disorder. Pharmacologic therapy begins with simple
      analgesics and education. In many patients, simple analgesics do not adequately
      control moderate arthritis pain, and nonsteroidal antiinflammatory drugs (NSAID)
      are substituted for or added to the analgesic therapy. While NSAID are effective
      in controlling pain in mild to moderate osteoarthritis (OA), they are associated
      with significant toxicity (most frequently gastrointestinal) and may even cause
      complications that result in death. Patients who experience the pain associated
      with arthritis would therefore benefit from the antiinflammatory and analgesic
      actions of agents that are devoid of significant toxicities. Cyclooxygenase-2
      (COX-2) inhibitors are being evaluated in clinical trials or are in development.
      These agents appear to inhibit only the COX-2 isoenzyme, which is produced
      largely during inflammation and is responsible for the biosynthesis of
      prostaglandins and other mediators of inflammation as well as sensitizers to
      pain. Because COX-2 inhibitors do not inhibit COX-1 isoenzyme activity at
      pharmacologic concentrations, they are devoid of many of the toxicities that are
      typical side effects of NSAID. Short term studies in dental pain, OA, and
      rheumatoid arthritis found that the COX-2 inhibitor celecoxib was an effective
      analgesic but did not cause gastroduodenal erosions. It has the potential to
      provide analgesia and antiinflammatory action in patients with arthritis without
      the side effects of NSAID. Further studies are required to substantiate these
      findings.

PMID- 9249649
TI  - Description of Topomyia irianensis n. sp. and new records of To. papuensis from
      Maluku and Irian Jaya, Indonesia (Diptera:Culicidae).
AB  - The adults, male genitalia, pupa, and larva of Topomyia (Topomyia) irianensis n.
      sp. from Irian Jaya, Indonesia, are described and illustrated. The new species is
      compared to closely related species, Topomyia dejesusi Baisas and Feliciano,
      1953, and Topomyia argyropalpis Leicester, 1908. Topomyia (Suaymyia) papuensis
      Marks was recorded for the first time from Maluku and Irian Jaya. This is the
      first record of the genus Topomyia from Maluku and Irian Jaya, Indonesia.

PMID- 9249650
TI  - Phlebotomine sand fly control using bait-fed adults to carry the larvicide
      Bacillus sphaericus to the larval habitat.
AB  - Sugar meals of plant origin are an important component of the sand fly diet. We
      show that sugar solution baits have potential as vehicles for phlebotomine sand
      fly control. In the laboratory, adult Phlebotomus duboscqi Neveu-Lemaire and
      Sergentomyia schwetzi (Adler, Theodor, and Parrot) that have consumed an aqueous
      sucrose solution containing Bacillus sphaericus Neide toxins and are subsequently
      eaten by larvae produce significant larval death (P < 0.01). In the field, when
      vegetation near animal burrows and eroded termite mounds was sprayed with sucrose
      solution with or without incorporation of the larval toxicant B. sphaericus, 40%
      of female sand flies fed in situ. Dispersing B. sphaericus-carrier sand flies
      caused significant larval mortality (P < 0.01) in resting and breeding sites in
      animal burrows 10-30 m from the sprayed vegetation for 2-12 wk posttreatment.
      Also, adult sand fly populations breeding and resting inside animal burrows were
      significantly reduced (P < 0.01) following direct application of the sucrose/B.
      sphaericus solution to the burrow entrances. This control effect lasted 4-10 wk
      post-treatment. The effect was not seen for sand fly populations breeding and
      resting inside eroded termite mounds. This approach may be useful for the
      application of biological control agents against phlebotomine sand flies in
      biotypes where larvae and adults use the same habitats.

PMID- 9249651
TI  - Selection-dependent trends of autogeny and blood feeding in an autogenous strain
      of Culex tarsalis (Diptera:Culicidae).
AB  - During successive en masse selection of autogeny in Culex tarsalis from parental
      to 20th generation, the autogenous oviposition capacity changed as follows: mean
      number of egg rafts/female and mean number of eggs/female increased
      significantly, from 0.11 to 0.56 and from 6.2 to 20.2, respectively; the mean
      size of the egg rafts decreased significantly, from 56.2 to 36 eggs/raft;
      autogeny rates increased significantly, from 18.6 to 65.2%; mean number of
      autogenous follicles/female decreased significantly, from 57.4 to 34; the
      hatching rate of autogenous egg rafts reduced significantly, from 88.3 to 75.4%;
      and the feeding rates of the females on a blood meal source during the 7th day
      postemergence increased significantly, from 62.8 to 71.1%. The autogeny rate
      determined by ovarian dissection was higher than that indicated by actual
      oviposition. As the age of females increased during the observed 10-day
      oviposition period, the mean number of egg rafts/female, the mean number of
      eggs/female, and the mean number of eggs/raft decreased successively, and
      scattered "light color" egg rafts became more common. Successive en masse
      selection enhanced autogeny and strengthened the bloodfeeding tendency in this
      facultative autogenous species.

PMID- 9249652
TI  - Response of Culex quinquefasciatus to visual stimuli.
AB  - The vision of Culex quinquefasciatus was studied in the laboratory. The
      attractiveness of colors (black, white, brown, yellow, blue, a skin tone) was
      evaluated with respect to the collection of Cx. quinquefasciatus in natural
      light, in the dark, and in ultraviolet light. Culex quinquefasciatus prefers both
      black and brown in natural light and ultraviolet light, but, as expected, there
      is no preference in the dark. There were no significant differences among the
      other 4 colors in natural light and ultraviolet light.

PMID- 9249653
TI  - Acute and sublethal effects of (S)-methoprene on some Australian mosquitoes.
AB  - Laboratory bioassays were used to determine the efficacy of (S)-methoprene
      against 7 species of Australian mosquitoes. The 90% lethal concentration (LC90)
      ranged from 0.17 ppb for Aedes vigilax to 6.54 ppb for Culex sitiens. The
      survival of adults exposed as larvae to 2 sublethal dosages of (S)-methoprene was
      compared to a control group. Little effect was noted for Cx. sitiens and Culex
      annulirostris. However, survival of male and female Ae. vigilax was significantly
      reduced and appeared to be dose related. Bloodfeeding success of female Ae.
      vigilax was also significantly reduced.

PMID- 9249654
TI  - Observations on multiple bloodfeeding in field-collected Culiseta melanura.
AB  - This study examined field populations of Culiseta melanura for evidence of
      partial blood meals and multiple feeding behavior. Engorged specimens that had
      1/3 or less abdominal distention together with eggs in stage I-II of ovarian
      development were recorded as mosquitoes that had taken partial blood meals.
      Multiple blood meals were credited to engorged specimens with fresh blood as well
      as partially digested blood surrounded with separate peritrophic membranes and
      eggs in stage III or IV of ovarian development. Results indicated that only 17 of
      532 Cs. melanura were captured with a partial meal, indicating that natural
      populations feed to repletion more than 95% of the time. Less than 1% of the
      specimens showed physical evidence of feeding on multiple hosts. Culiseta
      melanura appears to be highly efficient at obtaining a full blood meal and seems
      to be extremely reluctant to refeed once ovarian development has been initiated.
      As a result, multiple feeding does not appear to be important in the
      amplification of virus by this species.

PMID- 9249655
TI  - Field trial of Bacillus sphaericus strain B-101 (serotype H5a, 5b) against
      filariasis and Japanese encephalitis vectors in India.
AB  - A large-scale operational field trial was conducted from June 1993 to October
      1994 to evaluate the efficacy of Bacillus sphaericus (strain B-101, serotype
      H5a,5b) for control of the vectors of filariasis (Culex quinquefasciatus) and
      Japanese encephalitis (Cx. tritaeniorhynchus and Cx. vishnui) in Rourkela city.
      Application of B. sphaericus, when sprayed at 1 g/m2 in storm drains, wastewater
      pools, abandoned masonry tanks, peripheral paddy fields, ditches, and other small
      water collections and at 4 g/m2 in domestic septic tanks, significantly reduced
      larval and pupal counts (P < 0.0001) and significantly reduced the percentage of
      habitats containing larvae (3rd-4th instars) (P < 0.0001) as compared with
      routine antilarval measures. This in turn resulted in a reduction in the indoor
      density of disease vectors in particular and a reduction in mosquito nuisance in
      general. The trial demonstrated that B. sphaericus has good potential for use
      against disease vectors and mosquito breeding in polluted as well as clean
      waters.

PMID- 9249656
TI  - Importance of Hydrilla verticillata (hydrocharitaceae) as habitat for immature
      mosquitoes at the Ross River reservoir, Australia.
AB  - From November 1990 to November 1992, immature mosquitoes were sampled from the
      shoreline and from emergent beds of the submerged aquatic plant Hydrilla
      verticillata at the Ross River reservoir, northern Australia. Aerial mapping of
      Hydrilla beds was done in conjunction with sampling to estimate total immature
      mosquito numbers. Larvae of 7 species were found. Culex annulirostris. Anopheles
      annulipes s.l., and Anopheles amictus comprised 80.4% of the total. Peak larval
      densities occurred in the late wet season period in both habitat types (March to
      May) but Hydrilla generally supported higher densities, particularly of An.
      annulipes s.l. (43.7% of the total sample), than the shoreline habitats.
      Anopheles annulipes replaced Cx. annulirostris as the predominant taxon when 1990
      92 data were compared with data for 1985-86. The Hydrilla beds supported on the
      order of 5.6 x 10(9) immatures during the period of peak density. This suggests
      that where human exposure is of concern, mosquito control in habitats such as
      Hydrilla is warranted.

PMID- 9249657
TI  - Pesticide avoidance behavior in Anopheles albimanus, a malaria vector in the
      Americas.
AB  - The behavioral responses of 4 populations of Anopheles albimanus females to DDT,
      permethrin, and deltamethrin were characterized in excito-repellency tests. One
      test population (ST) from El Salvador has been maintained as a colony for 20
      years. A second population (ES) from Guatemala was colonized in 1992. Third and
      fourth populations consisted of field-caught specimens from Toledo District (TO)
      of southern Belize in 1994 and Corozal District (CO) of northern Belize,
      respectively. Females of ES, TO, and CO populations rapidly escaped from direct
      contact with treated surfaces for each of the 3 insecticides. Similarities in
      escape responses of insecticide-resistant (ES) versus insecticide-susceptible
      populations (TO, CO) suggest that there is no relationship between physiological
      and behavioral responses of An. albimanus populations to DDT, permethrin, and
      deltamethrin. Females from all but the ST colony escaped in greater numbers from
      chambers without direct contact with treated surfaces than from control chambers
      (P < 0.05). Few females from the ST colony escaped from test chambers, regardless
      of which insecticide was used or whether contact was allowed, indicating that the
      ST colony has lost its capability to respond to insecticides. Repellent responses
      were significant; but they were not pronounced in 30-min exposures, and they were
      very pronounced in 4-h exposures. We conclude that irritant and repellent
      responses of malaria vectors to insecticides are important components of malaria
      control operations.

PMID- 9249658
TI  - Efficacy of three synthetic pyrethroids against three mosquito species in
      Arkansas and Louisiana.
AB  - Adult mortality of Anopheles quadrimaculatus, Culex quinquefasciatus, and Aedes
      sollicitans was observed following ultra-low-volume (ULV) exposure to Responde,
      Permanone 31-66 RTU, and Scourge. Permanone 31-66 RTU (1:2.13, permethrin:PBO)
      and Scourge (1:3, resmethrin:PBO) were applied at 0.00175 lb AI/acre, while
      Responde (1:3, prallethrin:PBO) was applied at 0.001 lb AI/acre, and all were
      evaluated at 100, 200, and 300 ft. downwind of application. Significant mortality
      differences (P < or = 0.05) were observed among all compounds at 15 min and at 1,
      12, and 24 h posttreatment against An. quadrimaculatus and Cx. quinquefasciatus.
      Responde exhibited significantly greater (P < or = 0.05) control (knockdown)
      against An. quadrimaculatus at both 15 min and 1 h posttreatment than did
      Permanone 31-66 RTU or Scourge; however, some recovery occurred by 12 h
      posttreatment. At 15 min posttreatment, Responde and Scourge were significantly
      (P < or = 0.05) more effective against Cx. quinquefasciatus than Permanone 31-66
      RTU except at 300 ft. downwind, where Scourge was significantly (P < or = 0.05)
      more effective than either compound. No significant mortality differences (P < or
      = 0.05) were observed among the 3 compounds at 15 min, 1 h, 12 h, and 24 h
      posttreatment when tested against Ae. sollicitans. No significant mortality
      differences (P < or = 0.05) were observed between the 1:3 and 1:5 (prallethrin:
      piperonyl butoxide) formulations of Responde at any time posttreatment when
      tested against Ae. sollicitans.

PMID- 9249659
TI  - New strategies for the control of the parthenogenetic chironomid (Paratanytarsus
      grimmii) (Diptera:Chironomidae) infecting water systems.
AB  - Control of the midge, Paratanytarsus grimmii, infesting municipal water systems
      has proven to be difficult, because it is a parthenogenetic species that can
      oviposit as a pharate adult and reproduce within the system. Mean densities of P.
      grimmii in a midwestern USA water distribution system ranged from approximately
      140 to 560 individuals/sampling date, and all 4 instars and pupae were present
      throughout the sampling period. Two products were tested as potential chemical
      controls: Cat-Floc LS, a coagulant produced by the Calgon Corporation, and 35%
      hydrogen peroxide, a water purifier. The results of laboratory bioassays showed
      that Cat-Floc LS over a 15-day period was most effective against P. grimmii.

PMID- 9249660
TI  - Seasonal abundance and distribution of mosquitoes at a rural waste tire site in
      Illinois.
AB  - The species composition, abundance, and distribution of mosquito larvae in tires
      were determined on 3 dates at a relatively large rural tire dump (about 300,000
      tires) in southeastern IL (Jasper County). Several observations at this site
      differed from those in previous reports about mosquitoes in tireyards, including
      1) a relatively high percentage of tires positive for Aedes triseriatus larvae in
      an open-field area, 2) a greater abundance of Culex pipiens than Cx. restuans in
      late-season collections, 3) a seasonal change in the distribution of Aedes
      atropalpus larvae in tires from open field and edge of woods areas, and 4) the
      presence of Ae. albopictus as a major late-season species. Ae. albopictus adults
      were captured in sod-baited gravid traps along the edge of a wooded riparian area
      200 m from the tire pile.

PMID- 9249661
TI  - Efficacy of ALTOSID pellets and granules against Aedes aegypti in ornamental
      bromeliads.
AB  - The tank bromeliad Billbergia pyramidalis was treated with 2 doses (0.5 and 2 g)
      of ALTOSID Granules or Pellets for the control of Aedes aegypti L. Emergence
      inhibition (EI) for all mosquito pupae (including natural populations) in the
      center wells and leaf axils was > 90% for at least 6 and 12 months for both doses
      of granules and pellets, respectively. No significant difference in %EI was found
      between center wells and leaf axils.

PMID- 9249662
TI  - Genetic analysis of a larval color mutant, yellow larva, in Anopheles sundaicus.
AB  - One larval body color mutant, yellow larva (yl), was isolated from a newly
      established cyclic colony of Anopheles sundaicus. The inheritance pattern
      revealed that yellow larva was an autosomal recessive mutant.

PMID- 9249663
TI  - Diel patterns of pupation, emergence, and oviposition in a laboratory population
      of Aedes albopictus.
AB  - There was no apparent daily pattern of pupation in Aedes albopictus in the
      laboratory [14:10 h (L:D); lights on: 0600 h, lights off: 2000 h], but diel
      patterns of emergence and oviposition were influenced by mosquito body size.
      Emergence rate was highest in large-bodied male mosquitoes at 1600 h and in small
      males at 1000 h but was lowest in large and small males, respectively, at 2400 h
      and 0200 h. Peak emergence of females was at 1600 h, regardless of body size;
      lowest emergence was at 0400 h. Half of all ovipositions by large females in
      their first gonotrophic cycle (GC1) were at 2000 and 2200 h but at 1800 to 2000 h
      in the second gonotrophic cycle (GC2). In small females, oviposition in GC1 and
      GC2 was highest at 1800 and 1600 h, respectively, and lowest at 0400 h. Half of
      all ovipositions in small females were at 1600 to 1800 h.

PMID- 9249664
TI  - Discovery of a bromeliad-inhabiting Culex (micraedes) sp. in south Florida.
AB  - Immatures of a Culex (Micraedes) sp. were collected from bromeliads at 6 sites in
      Dade County, FL. This discovery represents the first time a member of this
      subgenus has been detected in the continental United States. The Cx (Micraedes)
      sp. was found in both native and exotic bromeliads, and at some sites this Culex
      occurred in these plants as frequently as Wyeomyia spp.

PMID- 9249665
TI  - Is it better to inhale? An examination of the medical use of marijuana
      controversy in the United States.

PMID- 9249666
TI  - HIV plasma viral load in the clinical setting: measurement and interpretation.

PMID- 9249667
TI  - Malnutrition associated with HIV/AIDS. Part One: Definition and scope,
      epidemiology, and pathophysiology.
AB  - A documented association exists between nutritional status and immunologic
      function, development, and outcome of infectious processes, and treatment-related
      toxicity and vital organ function. In persons with AIDS, nutritional deficits
      precipitate a cycle that results in a downward spiral of weight lost,
      malabsorption, diarrhea, anorexia, body image disturbance, and increased risk for
      morbidity and mortality. This article presents an overview of the malnutrition in
      HIV/AIDS patients. It critiques the current Centers for Disease Control's
      definitions of wasting syndrome, describes the incidence of weight loss,
      delineates the implications of untreated malnutrition, and traces the etiology of
      weight loss and contributing factors. This article serves as an introduction to
      HIV/AIDS related malnutrition. A subsequent article will review nursing
      implications and clinical management programs.

PMID- 9249668
TI  - Helping others: a response to HIV disease.
AB  - Previous research supports that helping behaviors can be as beneficial to the
      person providing the help as to the recipient. Ten individuals infected with HIV
      describe how helping others became an important strategy in helping them live
      with their diagnosis of HIV/AIDS. A grounded theory study was done to identify
      and describe psychosocial responses to being infected with HIV. Audiotaped
      interviews were analyzed using grounded theory methodologies. The core category
      that emerged from the data was fighting to survive. Taking care and restructuring
      one's life were the supporting concepts. Processes involved in taking care were
      everyday work and illness work. Helping others was one strategy of everyday work
      the participants found to be helpful in the fight to survive. The benefits of
      helping are described and the various ways of helping are presented in this
      article.

PMID- 9249669
TI  - Implementing a multidisciplinary HIV diarrhea critical pathway in the acute care
      setting.
AB  - Clinical pathways are the new strategy for managing hospital length of stay and
      cost in the changing, dollar-driven arena of health care. For patients with AIDS,
      HIV-related diarrhea is a potential source of increased morbidity that results in
      increased hospitalization and health care costs. This article describes the
      development and implementation of a multidisciplinary HIV Diarrhea Critical
      Pathway at Mount Sinai Medical Center of Greater Miami in South Florida. The
      focus of this article is on the nursing issues that arose during the piloting of
      the Diarrhea Critical Pathway and on the "how-tos" of its use. Initial evaluation
      of the first 3 years of using the diarrhea pathway is reported.

PMID- 9249670
TI  - Global issues in HIV/AIDS in children: an interview with Michael Gibbons.
      Interview by Marie Farrell.

PMID- 9249672
TI  - Should complex medication regimens be prescribed to people with a low probability
      of compliance?

PMID- 9249671
TI  - Needs assessment of caregivers of people with HIV/AIDS.
AB  - This descriptive study assessed 34 caregivers of people with HIV/AIDS to learn
      their perceived needs, concerns, and use of services. Results indicated the most
      common health problems of the care recipient were fatigue and weight loss; care
      recipients needed help with climbing stairs, walking, and bathing; caregivers
      helped with the household chores, transportation, and companionship; caregivers
      were concerned about coping with loss and responsibilities; caregivers had help
      from family, case manager, and neighbor; caregivers wanted help such as a
      companion and counseling. Discussion relates to the implications of the study for
      health care professionals.

PMID- 9249673
TI  - Factors affecting the radiologic appearance of peripheral bronchogenic
      carcinomas.
AB  - The use of high-resolution computed tomography and magnetic resonance imaging
      have allowed the detailed description of morphologic findings associated with
      lung cancer. In particular, the desmoplastic response of lung tissue to tumor
      growth has not been adequately described. This article reviews roentgenologic and
      pathologic correlations of primary lung carcinomas. An irregular or indistinct
      tumor margin may be caused by tumor infiltration, an irregular desmoplastic
      response to the tumor growth, or irregular contraction in the central portion of
      the tumor. Solid tumor growth, on the other hand, may be associated with a well
      defined tumor margin, with or without displacement of adjacent anatomical
      structures.

PMID- 9249674
TI  - Utility of low-dose helical CT as a second step after plain chest radiography for
      mass screening for lung cancer.
AB  - We evaluated the usefulness of low-dose helical computed tomography (CT) as a
      routine second step in patients screened for lung cancer with plain chest
      radiography (PCR). Of 5,437 people who underwent mass screening for lung cancer
      by PCR, further work-up was required for 230 because of abnormal findings. Of 221
      subjects who had CT as a second step, abnormal shadows were detected in 110 and
      no abnormal shadows were seen in 111. Screening CT (helical scan; beam
      collination, 10 mm; pitch of 2:20 mm/s; and tube current, 50 mA) detected 17 lung
      cancers, 87 benign lesions, and 6 extrapulmonary lesions, with an average
      diameter of 10 mm (range, 2-35 mm). All lung cancers were peripheral (12 stage I,
      4 stage IIIA, and 1 stage IV). In 40% of screened subjects, 37 with benign
      lesions and 7 with lung cancer (6 stage I), lesions were delineated only by
      screening CT. In conclusion, low-dose helical CT was found to be useful as a
      second step in patients who have been screened for lung cancer by PCR and can
      delineate the early stage of lung cancer.

PMID- 9249675
TI  - Intratumoral necrosis of lung carcinoma: a potential diagnostic pitfall in
      incremental dynamic computed tomography analysis of solitary pulmonary nodules?
AB  - The authors determined the pattern and enhancement range of necrotic lung
      carcinoma using incremental dynamic computed tomography (CT). Thirty-seven
      pathologically proven lung cancers (range, 8-57 mm in diameter) were evaluated
      using incremental dynamic CT. Scans were obtained before and 30 seconds, 2
      minutes, and 5 minutes after the onset of contrast material injection. Computed
      tomography numbers in circular regions of interest (60% of tumor diameter) were
      calculated, and the difference in CT number between nonenhanced and the scan
      showing maximum attenuation was determined. In cavitary necrotic carcinomas,
      regions of interest were established excluding areas of cavitation. Nine (24%) of
      37 lung carcinomas had intratumoral necrosis; four (11%) had noncavitary
      necrosis, and five (14%) had cavitary necrosis. Maximum attenuation of four
      noncavitary necrotic carcinomas (mean 31 +/- standard deviation 25 HU; range, -3
      56 HU) was lower than cavitary necrotic carcinomas (42 +/- 8 HU; range, 35-51 HU;
      p = 0.36) and non-necrotic carcinomas (48 +/- 17 HU; range, 25-91 HU; p = 0.07).
      All carcinomas showed maximum attenuation > or = 25 HU except for one noncavitary
      necrotic carcinoma (maximum attenuation = -3 HU; 36 mm in diameter). Noncavitary
      necrosis was recognized as low attenuation on noncontrast scan in two of four
      cases and as an unenhanced area on enhanced scan in four of four cases. Although
      noncavitary necrotic lung carcinoma may rarely show maximum attenuation < or = 15
      HU, necrotic material is recognized as unenhanced area on enhanced scan.

PMID- 9249676
TI  - Magnetic resonance imaging of rounded atelectasis.
AB  - This study describes the magnetic resonance imaging (MRI) findings of rounded
      atelectasis (RA) and compares them with computed tomography (CT) findings. The
      study sample comprised 15 cases of RA in which both MRI and CT were performed.
      The signal intensity of RA was higher than that of muscle and lower than that of
      fat on T1-weighted images, and similar to or lower than that of fat on T2
      weighted images. The atelectatic mass homogeneously enhanced after gadopentetate
      dimeglumine administration. Structures within and surrounding the RA were clearly
      depicted on MRI. The pulmonary vessels and bronchi converging toward the area of
      atelectasis (comet tail sign) were better demonstrated by sagittal or oblique
      sagittal MRI in six cases. RA and thickened pleurae were more clearly separated
      on T2-weighted images compared with CT. An infolded visceral pleura was
      demonstrated as a low-signal-intensity line in seven cases, and a small amount of
      entrapped pleural effusion was noted in one case. Although MRI should not be
      performed in all cases of suspected RA, it is useful, especially in delineating
      the internal structure of RA, such as the infolded visceral pleura.

PMID- 9249677
TI  - Hilar and mediastinal invasion of bronchogenic carcinoma: evaluation by thin
      section electron-beam computed tomography.
AB  - The diagnostic accuracy of thin-section incremental dynamic computed tomography
      (IDCT) using an electron-beam scanner in evaluating hilar or mediastinal invasion
      of bronchogenic carcinoma was assessed. Thirty-seven patients with proven
      bronchogenic carcinoma, contiguous with hilar or mediastinal structures,
      underwent IDCT. The area of contact was scanned using 19 contiguous 3-mm thick
      sections during injection of contrast material. The degree of contact between
      mass and pulmonary artery or vein and their distortion were recorded. Irregular
      thickening of the bronchial wall, soft tissue within the lumen, or distortion
      were used to determine airway involvement. Sixty-nine sites were assessed
      retrospectively and compared with pathology reports. The accuracy, sensitivity,
      and specificity in evaluating invasion of the pulmonary artery were 75.0%, 77.8%,
      and 71.4%, respectively. Limited reliability also was found for invasion of the
      main bronchus and "secondary" carina, with accuracies of 66.7% and 70.5%,
      sensitivities of 75.0% and 70.0%, and specificities of 57.1% and 71.4%,
      respectively. Thin-section IDCT with electron beam scanner is not accurate in the
      detection of hilar or mediastinal invasion by bronchogenic carcinoma.

PMID- 9249678
TI  - Magnetic resonance imaging of the postpneumonectomy chest: normal and abnormal
      findings.
AB  - To determine the normal findings at magnetic resonance imaging (MRI) of the
      postpneumonectomy space (PPS), and to evaluate the utility of MRI in detection of
      recurrent tumor in the postpneumonectomy chest, 32 MRI scans were performed in 31
      patients at varying time intervals after pneumonectomy. Eleven patients also had
      12 computed tomography (CT) scans performed at the same time to evaluate possible
      tumor recurrence. Of the 32 scans, 5 demonstrated complete obliteration of the
      fluid containing PPS, and 4 showed gas in the PPS; the remainder (n = 23)
      demonstrated persistence of fluid-filled spaces of varying size. The presence of
      a fibrotic rim of tissue was constant. In 11 patients with clinically suspected
      tumor recurrences, both CT and MRI were obtained: the two modalities performed
      with similar accuracy in diagnosing tumor recurrence at 16 sites; CT detected
      opposite-lung metastatic nodules not seen on MRI in one patient, and a rib
      metastasis described as "indeterminate" on MRI in a second patient. MRI detected
      a focus of recurrence in the PPS that was indeterminate on CT. There is
      considerable variability in the amount of fluid seen in the PPS on MRI. CT
      remains the procedure of choice for routine follow-up or in suspected tumor
      recurrence in the postpneumonectomy patient; MRI can be helpful if the CT scan is
      nondiagnostic or equivocal.

PMID- 9249679
TI  - Postpneumonectomy syndrome: another twist.
AB  - This report describes the clinical, radiographic, and surgical findings in a
      patient with a rare postoperative complication, the postpneumonectomy syndrome.
      To our knowledge, it is the first reported case of postpneumonectomy syndrome
      after left pneumonectomy in a patient with a left-sided aortic arch.

PMID- 9249680
TI  - Radiographic determination of total lung capacity in patients with pneumonectomy.
AB  - To determine whether total lung capacity (TLC) can be measured from plain chest
      radiographs in patients with pneumonectomy, we examined 20 such patients (17
      male, 3 female) who had pneumonectomy for lung carcinoma. In 16 patients the
      right lung was preserved, and in 4 the left. The TLC was measured with the helium
      dilution method and by planimetry of the anterior and lateral projections of the
      lung on chest radiographs, summing the anterior and lateral projected areas of
      the lung to a single value, S. The correlation between S and TLC by helium gas
      dilution was r = 0.95. Linear fit of TLC to S explained 99.5% of the variance in
      TLC, with the equation. The side resected did not influence the predictive value
      (p < 0.001). The interquartile range of the residual error was +/-130 ml, and
      standard error was 64 ml. Therefore in patients with pneumonectomy, TLC of the
      preserved lung may be estimated within +/-130 ml by planimetry of the anterior
      and lateral chest radiographs.

PMID- 9249681
TI  - Benign pulmonary lymphocytic infiltration and amyloidosis: computed tomographic
      and pathologic features in three cases.
AB  - The clinical radiologic, and pathologic features of three patients with a
      combination of pulmonary lymphocytic infiltration and amyloid deposition are
      presented. We report the distinctive high-resolution computed tomography features
      that are common to these cases.

PMID- 9249682
TI  - Magnetic resonance imaging of apical hypertrophic cardiomyopathy.
AB  - To assess the capability of magnetic resonance imaging (MRI) to define the
      presence, degree, and distribution of apical hypertrophic cardiomyopathy in
      patients of European descent, MRI examination was prospectively performed in
      patients diagnosed with hypertrophic cardiomyopathy on two-dimensional
      echocardiography. Twenty-five patients with hypertrophy located exclusively at
      the cardiac apex were the object of this study. Spin echo and gradient echo
      sequences were performed to evaluate the morphology, motility, and myocardial
      thickness of the left ventricle in diastole. In a short-axis gradient echo
      sequences from base to apex, septal, lateral, anterior, and posterior segments at
      the basal and apical levels were measured. A four-chamber view and horizontal
      long-axis images of the left ventricle were performed to measure the true apex. A
      concentric, symmetric distribution of hypertrophic myocardium was considered when
      the thickness was 1.5 cm or greater, with the four segments being affected to a
      similar degree. Asymmetric hypertrophy was considered when the wall thickness
      ratio was more than 1.3. Myocardial thicknesses at the apical level were 2.03 +/-
      0.60 cm (mean +/- standard deviation) at the true apex; the septal thickness was
      1.19 +/- 0.46 cm; lateral, 1.62 +/- 0.71 cm; anterior, 1.36 +/- 0.57 cm; and
      posterior, 1.28 +/- 0.53 cm. Based on the MRI findings, the distribution of
      apical hypertrophy was classified as symmetric (n = 2), asymmetric (n = 18), and
      true apex (n = 5). A spadelike configuration of the left ventricle was observed
      in only five cases. MRI demonstrates that in Western patients the morphologic
      spectrum of apical hypertrophy cardiomyopathy is quite wide and includes
      myocardial hypertrophy exclusively localized at the true apex.

PMID- 9249683
TI  - Diagnostic criteria for selenium toxicosis in aquatic birds: histologic lesions.
AB  - Chronic selenium toxicosis was induced in 1-yr-old male mallard ducks (Anas
      platyrhynchos) by feeding selenium, as seleno-DL-methionine, in amounts of 0, 10,
      20, 40, and 80 parts per million (ppm) to five groups of 21 ducks each for 16 wk
      during March to July 1988. All mallards in the 80 ppm group, three in the 40 ppm
      group, and one in the 20 ppm group died. Histologic lesions in mallards that died
      of selenosis were hepatocellular vacuolar degeneration progressing to
      centrolobular and panlobular necrosis, nephrosis, apoptosis of pancreatic
      exocrine cells, hypermaturity and avascularity of contour feathers of the head
      with atrophy of feather follicles, lymphocytic necrosis and atrophy of lymphoid
      organs (spleen, gut-associated lymphoid tissue, and lumbar lymph nodes), and
      severe atrophy and degeneration of fat. Histologic lesions in surviving mallards
      in the 40 ppm group, which had tissue residues of selenium comparable to mallards
      that died, were fewer and much milder than mallards that died; lesions consisted
      of atrophy of lymphoid tissue, hyalinogranular swelling of hepatocytes, atrophy
      of seminiferous tubules, and senescence of feathers. No significant histologic
      lesions were detected in euthanized mallards in the 0, 10 and 20 ppm groups.
      Based on tissue residues and histologic findings, primarily in the liver, there
      was a threshold of selenium accumulation above which pathophysiologic changes
      were rapid and fatal. Pathognomonic histologic lesions of fatal and nonfatal
      selenosis were not detected. Criteria for diagnosis of fatal selenosis in aquatic
      birds include consistent histologic lesions in the liver, kidneys, and organs of
      the immune system. Although histologic changes were present in cases of chronic
      non-fatal selenosis, these were inconsistent. Consistent features of fatal and
      non-fatal chronic selenosis were marked weight loss and elevated concentrations
      of selenium in organs.

PMID- 9249684
TI  - Hematological and plasma biochemical reference intervals in young white storks.
AB  - Hematological and plasma chemistry parameters were measured in 129 juvenile white
      storks (Ciconia ciconia), either wild or captive bred, April to June 1994. Wild
      storks were members of a colony in the Lozoya River Valley, Madrid, Spain. Red
      blood cells count, packed cell volume and hemoglobin increased significantly with
      age. White blood cells count, lymphocytes count and platelets decreased with age.
      Total solids, total proteins, fibrinogen, albumin, alpha, beta, gamma-globulins
      and urea increased with age. Differences between captive and wild birds were not
      notable.

PMID- 9249685
TI  - Lesions associated with infectious keratoconjunctivitis in alpine ibex.
AB  - Following a severe infectious keratoconjunctivitis (IKC) epizootic in free
      ranging alpine ibex (Capra ibex ibex) in Switzerland in 1993, 19 animals were
      examined from six different populations. Mucopurulent exudates, reddened
      conjunctiva and mononuclear inflammatory cell infiltration in the conjunctiva and
      the limbic area were observed in mild cases. In more severe cases, lesions ranged
      from perilimbic neovascularization to corneal edema, erosion, ulceration and
      neovascularization accompanied by infiltration of neutrophils. Sometimes an
      iridocyclitis was observed. In the most advanced stages, the cornea was
      perforated and an anterior synechia was present. Lesions found in ibex affected
      with IKC indicated a non-generalized, specific ocular disease. The other organs
      investigated did not show alterations suggestive of changes induced by agents
      which might cause IKC, including Chlamydia spp. and Mycoplasma. spp. The
      microbiological findings indicate that Mycoplasma conjunctivae is the primary
      pathogenic agent causing IKC in this species in Switzerland.

PMID- 9249686
TI  - Testicular atrophy in a mule deer population.
AB  - Monitoring mule deer (Odocoileus hemionus) on a former plutonium production site
      along the Columbia River at the Hanford Site, Washington (USA) revealed 27 (23%)
      of 116 adult males had unusually shaped, velvet-covered antlers and abnormally
      developed testicles. We captured 32 males to examine age-class differences and
      the ratio of affected to unaffected deer and determine whether affected testicles
      were atrophic or hypoplastic. We found testicular atrophy in most deer with
      velvet-covered antlers, primarily in animals older than 5 yr. Deer had marked to
      extreme stages of testicular atrophy, indicating permanent sterility. Decreased
      serum levels of testosterone and compensatory increased levels of luteininzing
      hormone and follicle stimulating hormone were detected in all affected males;
      thus, the gondopituitary hormonal pathway may have responded to abnormally low
      levels of testosterone in the affected animals. Brucella spp. antibodies in sera
      were not detected and 9 (90%) of 10 affected animals were seropositive for
      epizootic hemorrhagic disease virus (EHDV-2) and bluetongue virus (BTV-11) as
      compared to 12 (63%) of 19 unaffected animals; however, signs of other infectious
      diseases were not observed. Testicular degeneration generally exceeded that
      observed with nutritional disorders and poisons in domestic species. Also,
      severity of the atrophy and apparent lack of other affected tissues suggested
      that radiation may not be responsible. Testicular atrophy in mule deer has been
      reported elsewhere; however, neither prevalence has been as high nor or
      occurrence as well confined to a specific geographical area, as that observed at
      the Hanford Site. Furthermore, no physiological or age-related influences were
      described. Documenting the status of such variables and examining their
      relationships to this phenomenon is a crucial step in understanding the
      reproductive capacity of a wild deer population.

PMID- 9249687
TI  - Adrenal hyperplastic and degenerative changes in beluga whales.
AB  - Thirty stranded beluga whales (Delphinapterus leucas) from the St. Lawrence
      Estuary (Quebec, Canada) population and five animals from the Hudson Bay
      aboriginal hunt (North-west Territories, Canada) were examined. Twenty one
      animals from the St. Lawrence Estuary had mild to severe adrenal lesions and four
      whales from the Hudson Bay population were affected by minimal adrenal changes.
      Cortical hyperplasia was observed in 24 adult beluga whales all from the St.
      Lawrence Estuary. Bilateral cortical cysts and cellular vacuolar degeneration
      were observed in the adrenal glands of 19 beluga whales from both populations.
      The cysts, filled with a cortisol-rich liquid, were present in both sexes. Beluga
      whales with adrenal cysts were significantly older than animals without cysts,
      and the severity of the lesions increased with age. Nodular hyperplasia of the
      medulla was observed in seven of the beluga whales, all from the St. Lawrence
      Estuary population. All lesions could be part of a normal aging process. The
      adrenocortical lesions might be due to stress or adrenocorticolytic xenobiotics,
      while the medullary hyperplasia might be caused by hypoxia or exposure to
      estrogenic xenobiotics.

PMID- 9249688
TI  - Clinical and pathological characterization of northern elephant seal skin
      disease.
AB  - From 1984 through 1992, staff at The Marine Mammal Center (TMMC, Sausalito,
      California, USA) examined 207 northern elephant seals (Mirounga angustirostris)
      with a condition of unknown etiology called northern elephant seal skin disease
      (NESSD). The skin lesions were characterized by patchy to extensive alopecia and
      hyperpigmentation, punctate or coalescing epidermal ulceration, and occasionally,
      massive skin necrosis. Microscopic lesions included ulcerative dermatitis with
      hyperkeratosis, squamous metaplasia and atrophy of sebaceous glands. All diseased
      seals were less than 2 years of age and suffered from emaciation, depression, and
      dehydration. Mortality from septicemia increased significantly with severity of
      skin ulceration. Compared to 14 apparently unaffected seals, diseased seals had
      depressed levels of circulating thyroxine, triiodothyronine, retinol, serum iron,
      albumin, calcium, and cholesterol. Levels of alanine aminotransferase, aspartate
      aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, blood
      urea nitrogen, and uric acid were elevated. Morphometrically, diseased animals
      were approximately 15% smaller than normal seals of the same sage. Serum and
      blubber concentrations of 36 polychlorinated biphenyl congeners (sigma PCB) and
      dichloro-diphenyl-dichloroethylene (p,p'-DDE) were negatively correlated with
      body mass. Mean concentrations of sigma PCB and p,p'-DDE in serum in diseased
      seals were elevated as compared to apparently normal seals. Etiology of this
      syndrome remains unknown, but the possibility of PCB toxicosis cannot be ruled
      out.

PMID- 9249689
TI  - Herpesvirus infection in stranded Pacific harbor seals of coastal California.
AB  - Histopathological examination revealed multifocal acute to chronic adrenal
      necrosis in 74 of 162 (45%) Pacific harbor seal pups (Phoca vitulina richardsi)
      dying during rehabilitation following live stranding along the coast of central
      and northern California (USA). Necrotic adrenal cells contained amphophilic,
      smudgy intranuclear inclusion bodies that were stained positive for DNA. Fifty of
      these seals also had lesions typical of sepsis, bacterial omphalophlebitis,
      pneumonia or gastroenteritis. Twenty four seals had no lesions other than thymic
      atrophy and occasional multifocal hepatic necrosis. Prior to death, affected
      seals had a marked lymphopenia. Electron microscopy revealed unenveloped
      intranuclear hexagonal to round viral particles approximately 100 nm in diameter,
      and cytoplasmic enveloped virions approximately 160 nm in diameter. These were
      morphologically consistent with herpesvirus. Inoculation of phocine adrenal and
      kidney cell lines with an adrenal tissue homogenate from affected animals
      produced a cytopathic effect in 5 days. Electron microscopy of cell cultures
      showing this cytopathic effect revealed similar viral particles to those observed
      in affected adrenal glands. Cases with characteristic inclusion bodies were
      observed in 42 of 95 (44%) male and 32 of 67 (47%) female seals. Affected animals
      had been in rehabilitation 0 to 63 days and were below average birth weight for
      this species.

PMID- 9249690
TI  - Serologic survey for phocid herpesvirus-1 and -2 in marine mammals from Alaska
      and Russia.
AB  - Blood samples were collected from 1,042 marine mammals off the coast of Alaska
      (USA) and Russia during the period 1978 to 1994. Eight species of pinnipeds were
      represented. Sera were tested for presence of neutralizing antibodies to both the
      PB84 isolate of phocid herpesvirus-1 (PhHV-1) and the 7848/Han90 strain of phocid
      herpesvirus-2 (PhHV-2). Species-specific antibody prevalences ranged from 22% to
      77% for PhHV-1 and 11% to 50% for PhHV-2. Species-specific antibody prevalences
      for PhHV-1 were greater than or equal to prevalences for PhHV-2. For both viruses
      and each host species, differences in antibody prevalences were not related to:
      (1) sex, (2) location of capture, or (3) year of collection. Antibody prevalence
      of PhHV-1 in walruses (Odobenus rosmarus) could be quantitatively predicted as a
      function of age. These two viruses have distinct biological properties and based
      on current data the epizootiology of the two viruses is different, as well. No
      evidence of herpesvirus-induced mortality has been detected in areas included in
      this survey. Based on results of this survey, neither PhHV-1 nor PhHV-2 are
      considered significant mortality factors in mammals which inhabit the marine
      environment off the coast of Alaska or Russia.

PMID- 9249691
TI  - Antibodies to multiple tick-borne pathogens of babesiosis, ehrlichiosis, and Lyme
      borreliosis in white-footed mice.
AB  - Serum samples from Peromyscus leucopus (white-footed mouse), collected in
      Connecticut (USA) in 1983, 1985, and during 1990 to 1993, were analyzed by an
      enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody (IFA)
      staining methods for antibodies to Borrelia burgdorferi (strain 2591), Babesia
      microti, Ehrlichia chaffeensis (Arkansas strain), and Ehrlichia equi (MRK
      strain). Of the 294 serum samples tested, 160 (54%) contained immunoglobulins to
      one or more of these pathogens. There were antibodies to two or more etiologic
      agents in 77 (48%) of the seropositive mice. Although it was uncommon to detect
      coexisting antibodies to all four pathogens (n = 5 positive mice), E. chaffeensis
      reactive antibodies or immunoglobulins to E. equi were present along with those
      produced to B. burgdorferi and B. microti in 24 other mice. These rodents carry
      antibodies to several tick-borne pathogens at numerous sites in Connecticut and
      may play a role in the epizootiology of ehrlichiosis as well as babesiosis and
      Lyme borreliosis.

PMID- 9249692
TI  - Serologic survey for Trichinella spp. in grizzly bears from Alaska.
AB  - Blood was collected from 878 grizzly bears (Ursus arctos) in seven geographic
      areas of Alaska from 1973 to 1987. An enzyme-linked immunosorbent assay procedure
      was used to test sera for evidence of exposure to Trichinella spp. Serum antibody
      prevalence ranged from 5% (10 positive of 196 tested) in the Southern Region of
      the state to 83% (355 of 430 tested) in the Northern Region. These major
      discrepancies may be a result of differing food habits of bears in the major
      geographic areas. Prevalence was higher in older age cohorts. Neither year-of
      collection nor sex had a significant effect on prevalence.

PMID- 9249694
TI  - Mortality in fledgling great horned owls from black fly hematophaga and
      leucocytozoonosis.
AB  - Black fly feeding alone and in concert with Leucocytozoon spp. infection caused
      mortality in fledgling great horned owls (Bubo virginianus) in the Yukon, Canada
      1990 to 1991. These mortalities occurred during a year of food shortage
      corresponding with a decline in the population of snowshoe hare (Lepus
      americanus), the main prey for great horned owls. We hypothesize an interaction
      between food availability and the consequences of host-parasite interactions.

PMID- 9249693
TI  - Toxoplasmosis in wild mammals from the Czech Republic.
AB  - The prevalence of Toxoplasma gondii was determined in wild mammals in the Czech
      Republic from 1981 to 1990. The biological prevalence of T. gondii was < 1% in
      insectivores (n = 578), 12% in carnivores (n = 112), 1% in rodents except
      muskrats (Ondatra zibethicus) (n = 5,163), 24% in muskrats (n = 437), 5% in
      lagomorphs (n = 293), 0% in ruminants (n = 456), and 2% in wild boars (Sus
      scrofa) (n = 136). The seroprevalence (Sabin-Feldman dye test, titre > or = 1:4)
      of T. gondii was 15% in ruminants (n = 421), and 15% in wild boars (n = 124).
      Antibodies to T. gondii also were found in four of 10 carnivores. Toxoplasmosis
      is a common infection in wild mammals from the Czech Republic, but its prevalence
      varies considerable according to taxonomic groups and different localities where
      wild mammals live.

PMID- 9249695
TI  - Helminths and arthropods of black and white rhinoceroses in southern Africa.
AB  - Helminths and arthropods were collected and quantified from two black
      rhinoceroses (Diceros bicornis bicornis) and one white rhinoceros (Ceratotherium
      simum), and ticks from an additional four black and two white rhinoceroses in
      southern Africa. The helminths of a black rhinoceros from the Republic of South
      Africa and one from Namibia were quantitatively measured and recorded for each
      compartment of the alimentary tract. Probstmayria vivipara was the most abundant
      parasite in each animal. A recently described nematode, Diceronema versterae, was
      found in the stomach of one animal. Draschia megastoma was present in the
      descending colon of the same animal, but it was twice the size of similar
      specimens reported from equids and the typical granulomatous lesions caused by
      this nematode in horses were not observed. New records of other helminths from
      rhinoceroses include Parabronema roundi, Kiluluma sp., Kiluluma goodeyi, Kiluluma
      magna, Khalilia rhinocerotis, Oxyuris karamoja and Anoplocephala gigantea. The
      stomach bot, Gyrostigma pavesii, was collected from one black and one white
      rhinoceros. Ticks collected from the black rhinoceroses were Amblyomma hebraeum,
      Dermacentor rhinocerinus, Rhipicephalus maculatus, Rhipicephalus muehlensi and
      Haemaphysalis silacea. The two white rhinoceroses were infected with A. hebraeum,
      D. rhinocerinus, Hyalomma truncatum, Rhipicephalus simus, Rhipicephalus
      appendiculatus and Rhipicephalus zambeziensis.

PMID- 9249696
TI  - Helminths in ruffed grouse at the host's southeastern range boundary.
AB  - Carcasses of 268 ruffed grouse (Bonasa umbellus) collected in eastern Tennessee
      (USA) from October 1983 through February 1988 were examined between 16 January
      1985 and 25 April 1988 for non-filarioid helminths. Three nematode species and
      one cestode species were found. The two most common parasites were the cecal worm
      Heterakis bonasae (81% prevalence, mean intensity +/- SD of 62 +/- 114) and the
      tapeworm Echinolepis carioca (27% prevalence, 30 +/- 73 mean intensity). Age and
      sex of host were sufficient to predict infection by both common species.
      Condition of host and year and month of collection also had significant effects
      on prevalence. Intensity of cecal worm infection varied with age and condition of
      host and with region and month of collection.

PMID- 9249697
TI  - Extracting protostrongylid nematode larvae from ungulate feces.
AB  - A major weakness of the Baermann funnel technique for extracting nematode larvae
      from feces is the funnel. As many as 67% of Parelaphostrongylus tenuis first
      stage larvae lodged on the sloping surface of glass Baermann funnels. The number
      of larvae collected after 24 hr was not significantly correlated with total
      numbers in the samples, whether feces were supported over tissue paper or over
      window screening. Instead, we collected about 8 times as many larvae and achieved
      a significant relationship between larvae collected and the total numbers present
      when pelleted fecal material was submerged over screening in vertical-sided
      beakers. The methodology of this more efficient and more accurate way of
      estimating numbers of protostrongylid larvae is described. Most larvae were
      located on and in the mucous layer covering fecal pellets and readily left fresh
      pellets emersed in water; 72% of these larvae left after 6 min and only 11%
      remained after 1 hr. Larvae in water at room temperature sank as fast as 6
      cm/min, but those close to a vertical glass surface sank more slowly (97% sank
      18.5 cm in 105 min).

PMID- 9249698
TI  - Edwardsiellosis in wild striped bass from the Chesapeake Bay.
AB  - The first epizootic of edwardsiellosis, caused by Edwardsiella tarda, is
      described. The epizootic occurred in the Chesapeake Bay, Maryland (USA) during
      the summer and autumn of 1994, and affected wild adult striped bass (Morone
      saxatilis). Clinical signs included numerous irregular coalescing hemorrhagic
      ulcers on the body and fins that were distinctly malodorous. Internally, the body
      cavity was filled with abundant yellowish or sanguinous mucoid fluid, and the
      visceral organs had multiple tiny white foci. The intestines contained thick
      white opaque mucus. Histopathological lesions included ulcerative dermatitis,
      cardiac endothelial hyperplasia, and necrotic foci and granulomata in multiple
      organs. A bacterium isolated in pure culture was characterized taxonomically and
      serologically as the wild-type or classical biotype of E. tarda: In infectivity
      trials, it was pathogenic for striped bass, gilthead seabream (Sparus aurata),
      and turbot (Scophthalmus maximus) with an LD50 of about 10(5) cells; however, the
      isolate was non-virulent for mice (LD50 > 10(8) cells). The isolate also was
      resistant to the bacteriolytic activity of normal fish skin mucus.

PMID- 9249699
TI  - Mycoplasmas in wild turkeys living in association with domestic fowl.
AB  - One hundred and nineteen Merriam's wild turkeys (Meleagris gallopavo merriami)
      and 31 domestic chickens coexisting on a ranch in west-central Colorado (USA)
      were surveyed for mycoplasmosis by serologic and cultural methods. Although no
      clinical signs were apparent in any wild turkeys tested, 51 (43%) had positive
      rapid plate agglutination (RPA) reactions for M. gallisepticum (MG) and/or M.
      synoviae (MS); 37% of 56 adults and 48% of 63 subadults were classified as
      positive reactors to MG and/or MS. No turkeys tested in 1992 (n = 61) and 17
      (29%) of 58 turkeys tested in 1993 were RPA-positive for M. meleagridis (MM).
      Hemagglutination inhibition (HI) test results were negative for MG, MS and MM as
      were most enzyme-linked immunosorbent assay (ELISA) test reactions (MG = 99%, MS
      = 93%, MM = 87%). Immunoblotting showed mild to moderate reactivity to MG
      proteins in 49% of 41 samples tested. Most chickens were strongly positive for MS
      by RPA (81%), HI (58%) and ELISA (87%); 48% also were positive for MG by RPA but
      all were MG-negative by HI and ELISA. No pathogenic mycoplasmas were isolated
      from either group of birds. Mycoplasma gallopavonis was commonly identified from
      the wild turkeys, and M. gallinaceum was isolated from both the chickens and wild
      turkeys. In a transmission study conducted in 1994, disease-free domestic turkeys
      failed to seroconvert when co-housed with wild turkeys from this population that
      were RPA-positive for MG. Collectively, the results of this study were
      inconclusive regarding the status of pathogenic mycoplasmas within this wild
      turkey population.

PMID- 9249700
TI  - Rangiferine brucellosis on Baffin Island.
AB  - The standard tube agglutination test (STAT) and the complement fixation test
      (CFT) were used to assess the seroprevalence of antibodies to Brucella spp. in
      caribou (Rangifer tarandus) from three populations on Baffin Island, Canada.
      During late winter from 1983 to 1986, sera from 17 of 40 North Baffin (43%), 11
      of 33 Northeast Baffin (33%) and 12 of 82 South Baffin (15%) adult caribou had
      antibodies in the STAT at 1:50 or the CFT at 1:5. Seroprevalence increased as
      caribou matured with one (4%) of 25 calves, four (13%) of 31 yearlings, and 40
      (26%) of 155 adult caribou being positive. However, seroprevalence did not differ
      with sex in any age class. Positive antibody titers were higher in adult females
      sampled in May, 3 to 4 wk before parturition, than in adult females sampled in
      late March and April. The strength of positive titers did not differ with the
      time of sampling among adult males. Pathologic signs of brucellosis were found in
      three (13%) of 23 caribou that were assumed to have active infections (caribou
      with CFT titers > 1:160). Brucella suis biovar 4 was isolated from 24 (60%) of 40
      caribou from which lesions were submitted. Between 1986 and 1990, the annual
      incidence of reported human (Homo sapiens) cases averaged 3.4 (34:100,000) on
      Baffin Island.

PMID- 9249701
TI  - Pasteurella spp. in sympatric bighorn and domestic sheep.
AB  - Domestic sheep were sighted at different times from 1991 to 1993 on four Nevada
      (USA) ranges occupied by bighorn sheep. Nasal and pharyngeal swab samples were
      collected from both sheep species and cultured to determine if any strains of
      Pasteurella spp. were shared on range conditions after contact of the two
      species. Pasteurella spp. were isolated from all 38 bighorn sheep and 16 of 17
      domestic sheep included in this study. The isolates were characterized on the
      bases of species, biotype, serotype, biogroup, and restriction enzyme analyses
      (REA) as well as ribotyping of bacterial DNA. A P. haemolytica biotype 3,
      biogroup 11 isolate from a domestic sheep had biochemical, REA, and ribotype
      profiles which were identical to those of isolates from three bighorn sheep on
      the same range. None of the other isolates were found to be common to the two
      sheep species. Disease was not detected in any of the bighorn populations.
      However, bighorn sheep populations were extirpated on two ranges while increasing
      on the other two, including the range on which P. haemolytica biotype 3, biogroup
      11 strain was isolated. Declining sheep numbers were not correlated with the
      presence of any one strain of Pasteurella spp from the sheep.

PMID- 9249702
TI  - Effect of simulated stress on susceptibility of bighorn sheep neutrophils to
      Pasteurella haemolytica leukotoxin.
AB  - We examined the effects of simulated stress on susceptibility of Rocky Mountain
      bighorn sheep (Ovis canadensis canadensis) neutrophils to Pasteurella haemolytica
      leukotoxin in a blocked, crossover experiment. Ten captive-raised bighorn sheep
      were sampled 10 hr after separate administrations of long-acting
      adrenocorticotrophic hormone (ACTH) gel and normal saline (control). We then
      compared in vitro leukotoxin-dependent neutrophil death rates after exposure to
      culture supernatants from four unique P. haemolytica isolates (one from domestic
      and three from bighorn sheep). Simulated stress effects were evidenced by
      elevated (P = 0.002) mean plasma cortisol concentrations, more neutrophils (P =
      0.037), and fewer lymphocytes and eosinophils (P < or = 0.043) in ACTH-treated
      bighorn sheep. Maximum leukotoxin-dependent neutrophil death rates were > or =
      61% for three of four P. haemolytica isolates tested. For all three cytotoxic
      isolates, neutrophil death rates at 150 micrograms/50 microliters supernatant
      were about 1.13 times higher (P = 0.0001) after bighorns received ACTH; for two
      of these, overall neutrophil death rates were higher (P < or = 0.001) in ACTH
      treated bighorn sheep. Although variable leukotoxin production among P.
      haemolytica strains appeared principally responsible for differences in
      leukotoxin-dependent neutrophil death rates, susceptibility of bighorn sheep
      neutrophils to leukotoxin was increased by prior exposure to elevated plasma
      cortisol concentrations. It follows that if similar processes occur in
      neutrophils and alveolar macrophages in vivo, they could contribute to greater
      susceptibility of stressed bighorn sheep to pneumonic pasteurellosis.

PMID- 9249703
TI  - Experimental infection of deer with bovine viral diarrhea virus.
AB  - In order to determine the susceptibility of deer to infection with bovine viral
      diarrhea virus (BVDV), four mule deer (Odocoileus hemionus) fawns and one white
      tailed deer (O. virginianus) fawn were inoculated intranasally with the New York
      1 strain of BVDV originally isolated from cattle. None of the animals developed
      clinical signs of illness. Virus was isolated from white blood cells from four
      fawns on one or more occasions from day 2 through day 15 post-inoculation (PI)
      indicating that infection and systemic spread of BVDV had occurred. In addition,
      virus was isolated from nasal swabs from three fawns, one to three times, from
      day 2 through day 8 PI. Four fawns had virus neutralizing antibody titers to two
      strains of BVDV prior to inoculation and all developed greater than four-fold
      increases in virus neutralizing antibody titers by 3 wk PI. No gross lesions of
      bovine viral diarrhea were detected at necropsy approximately 3 mo PI. A variety
      of nonspecific lesions were detected by histopathology. Based on these findings,
      mule and white-tailed deer are susceptible to infection with BVDV. Isolation of
      virus from nasal swabs is evidence that BVDV could be transmitted by deer via
      direct contact.

PMID- 9249704
TI  - In vitro replication of epizootic hemorrhagic disease and bluetongue viruses in
      white-tailed deer peripheral blood mononuclear cells and virus-cell association
      during in vivo infections.
AB  - In vitro and in vivo infections were conducted to determine if the epizootic
      hemorrhagic disease (EHD) and bluetongue (BT) viruses would replicate in
      peripheral blood mononuclear (PBM) cells of white-tailed deer (Odocoileus
      virginianus). All of the North American EHD and BT viruses (EHD virus serotypes 1
      and 2, and BT virus serotypes 2, 10, 11, 13, and 17) replicated in vitro in
      cultures of white-tailed deer PBM cells. However, this replication appeared to be
      monocyte-dependent and was not enhanced by lymphocyte blastogenesis induced by
      the addition of concanavalin A. In white-tailed deer infected with either EHD
      virus serotype 2 or BT virus serotype 10, virus could be isolated consistently
      from PBM cells only from post-infection day 4 through 8, although they remained
      viremic through post-infection day 21. In deer, highest viral titers were
      associated with the erythrocyte fraction, and in no cases did viral titers
      detected in the platelet, PBM cell or polymorphonuclear cell fractions approach
      titers observed in whole blood. In the in vitro infections of white-tailed deer
      erythrocytes, the EHD and BT viruses were associated with pits in the erythrocyte
      membrane. This association may be important in the long-term viremia observed in
      deer.

PMID- 9249705
TI  - Host defense responses associated with experimental hemorrhagic disease in white
      tailed deer.
AB  - Our objectives were to examine the immunity conferred by epizootic hemorrhagic
      disease virus serotype 2 (EHDV-2) infection in white-tailed deer (Odocoileus
      virginianus) and determine if this immunity was protective during challenge with
      homologous (EHDV-2) or heterologous (bluetongue virus serotype 10; BTV-10) virus.
      Trials were conducted in the fall of 1992 and 1993. In the first experiment,
      naive white-tailed deer were infected intradermally and subcutaneously with EHDV
      2 and monitored via physical examinations, complete blood counts, alpha and beta
      interferon (IFN) assays, viral isolation, and serology. Infected deer had a wide
      range of clinical signs in response to infection. Eleven of the 16 deer had body
      temperature elevations > or = 0.5 C between post-infection day (PID) 4 and 8.
      Infected deer had decreased lymphocyte counts between PID 6 and 10 that returned
      to normal levels by PID 17. Severely lymphopenic animals had the most severe
      clinical signs; five of 10 deer with lymphocyte counts less than 1000
      cells/microliters succumbed to the infection. Viremia was detected in all 16 EHDV
      2 infected animals by PID 4, and peak viremias occurred between PID 4 and PID 10.
      Three deer remained viremic until PID 56, the study endpoint. Interferon was
      first detected between PID 2 and 6. Peak alpha and beta IFN levels coincided with
      peak viremia in 11 deer. Precipitating and neutralizing antibodies were detected
      in infected deer by PID 10. In the second experiment, convalescent deer were
      challenged subcutaneously and intradermally with either EHDV-2 or BTV-10 and
      similarly monitored. Virus was detected in the blood of all four deer challenged
      with BTV-10, but viremia was not detected in three EHDV-2-challenged deer.
      Temperature fluctuations, blood cell parameter changes, and IFN and antibody
      responses seen in BTV-10-challenged deer were similar to those seen in the
      initial experiment. Deer challenged with EHDV-2 had mildly increased
      temperatures, but minimal IFN response and lymphocyte alterations.

PMID- 9249706
TI  - Antibody responses of red wolves to canine distemper virus and canine parvovirus
      vaccination.
AB  - Twenty captive red wolves (Canis rufus), including 16 intended for release into
      Great Smoky Mountains National Park, Cades Cove, Tennessee (USA), and four housed
      at Knoxville Zoological Gardens, Inc., Knoxville, Tennessee, were evaluated for
      immunologic response to vaccination between June 1994 and April 1995. Wolves were
      vaccinated with modified-live (MLV) canine distemper virus (CDV) and canine
      parvovirus type-2 (CPV2). Sera were collected, and immunofluorescent staining was
      performed for determination of immunoglobulin titers (CDV IgM, CDV IgG, and CPV2
      IgG). A capture enzyme-linked immunosorbent assay was performed for validation
      purposes, to confirm the reactivity of our standard diagnostic reagents with red
      wolf serum. All wolves produced a measurable antibody response to CDV and CPV2
      vaccination. Titers against CDV and CPV2 varied widely among individual wolves,
      but between-litter differences in mean titers were not significant. No consistent
      response between the degree of response to CDV versus CPV2 vaccination was
      observed in individual wolves. No differences were seen between IgG responses of
      pups vaccinated with univalent vaccines given concurrently or during alternating
      weeks. Pups had an IgG response to CDV and CPV2 vaccination as early as 9 wk of
      age. Mean post-vaccination IgG titers against CDV were at or above the level
      normally measured in vaccinated domestic dogs. Mean post-vaccination IgG titers
      against CPV2 were below the level normally measured in domestic dogs. Adult
      previously-vaccinated wolves had measurable CDV and CPV2 IgG titers more than 1
      yr after vaccination, but did not have significant IgG titer increases after
      revaccination. We conclude that red wolves are capable of producing an antibody
      response after vaccination with commercial canine products but that their
      response to CPV2 vaccination was minimal. This response can be assayed using
      tests developed for domestic dogs.

PMID- 9249707
TI  - Comparison of three formulations of alpha-chloralose for immobilization of Canada
      geese.
AB  - The effectiveness of an alpha-chloralose (AC)-corn oil suspension, an AC
      margarine mixture, and AC tablets were compared for immobilizing Canada geese
      (Branta canadensis). Responses to AC immobilization also were compared in male
      and female Canada geese. There was no difference in mean time to first effects or
      mean time to capture between male and female geese dosed with 30 mg/kg AC in
      orally-administered bread baits. Recovery times (< or = 24 hr) also were similar
      between sexes. Mean (+/-SE) time to first effects for geese immobilized with AC
      tablets in bread baits (19 +/- 3 min) was significantly less than mean time to
      first effects for geese immobilized with AC in margarine (28 +/- 6 min) or AC in
      corn oil (32 +/- 7 min) applied to bread baits (n = 12 geese/treatment).
      Respective mean times to capture geese immobilized with AC tablets, AC-margarine,
      and AC-corn oil were not significantly different at 62 +/- 25, 89 +/- 48, and 88
      +/- 30 min, respectively. Ten, 11 and, seven geese immobilized with AC tablets,
      AC-margarine, and AC-corn oil recovered within 24 hr, respectively; all geese
      recovered within 28 hr. Male and female Canada geese respond similarly to AC
      immobilization, at least during molt, and AC mixed with margarine or AC in tablet
      form is at least as effective as the presently used AC-corn oil suspension. AC
      tablets or AC-margarine also would be more practical for some field situations.
      Additional development of AC tablets will be required prior to field use for
      capturing nuisance waterfowl.

PMID- 9249708
TI  - Reversible immobilization of free-ranging polar bears with medetomidine-zolazepam
      tiletamine and atipamezole.
AB  - The objective of this study was to determine if the potent alpha 2 agonist,
      medetomidine, and its specific antagonist, atipamezole, could be effectively used
      to immobilize polar bears (Ursus maritimus). Specifically, our goal was to
      develop a drug combination containing medetomidine that addressed some of the
      problems such as prolonged recovery time, non-reversibility, and poor analgesia
      that have been identified with the currently preferred drug combination,
      zolazepamtiletamine (Telazol or Zoletil). During 1995 and 1996, 51 free-ranging
      polar bears along the western coast of Hudson Bay, Canada, were immobilized with
      a combination of medetomidine, zolazepam, and tiletamine (MZT). Immobilization
      with MZT was characterized by a short induction time, low volume, reliable and
      predictable immobilization and reversibility, adequate analgesia, and relative
      safety in handling for field personnel. Few adverse physiological effects were
      observed in any target animals with the exception of a single bear which
      convulsed and died shortly after it was reversed from anesthesia with
      atipamezole. We conclude that MZT is an effective drug combination for
      immobilizing polar bears. However, because of an unexplained mortality, further
      investigation of the physiological effects of MZT and atipamezole is warranted.

PMID- 9249710
TI  - Serologic evidence of Jamestown Canyon virus infection in white-tailed deer
      populations from Connecticut.
AB  - We determined the prevalence and distribution of Jamestown Canyon (JC) virus
      antibody in white-tailed deer (Odocoileus virginianus) populations in
      Connecticut, USA. Sera were collected from hunter-killed deer during 1993.
      Antibody to JC virus was detected by enzyme-linked immunosorbent assay (ELISA) in
      92 (21%) of 446 deer sera, and was uniformly distributed among geographic sites.
      Twenty-one ELISA-positive sera were tested and confirmed positive by plaque
      reduction neutralization testing. This represents the first serologic evidence of
      JC virus in a reservoir host population from the northeastern United States. No
      cross-reactivity was seen with California encephalitis, Keystone, or snowshoe
      hare viruses, but a varying degree of cross-reactivity was obtained with Guaroa,
      Jerry Slough, La-Crosse, San Angelo, and trivittatus viruses. We conclude from
      this investigation and previous isolations of JC virus from mosquitoes in the
      state that JC virus occurs enzootically in Connecticut.

PMID- 9249709
TI  - Physiological effects of medetomidine-zolazepam-tiletamine immobilization in
      black bears.
AB  - A combination of medetomidine-zolazepam-tiletamine (MZT) was used to immobilize
      four black bears (Ursus americanus). The drugs were used at a dose of
      approximately 52 micrograms/kg of medetomidine, 0.86 mg/kg of zolazepam, and 0.86
      mg/kg of tiletamine. Induction occurred in 6.3 +/- 3.3 min (mean +/- SD). The
      combination produced minimal adverse cardiopulmonary effects. Hypertension
      occurred in all four bears. Oxygenation and ventilation was good in three of the
      four bears. One bear demonstrated slight hypoxemia and hypoventilation at 15 min
      following drug administration. At one 1 hr following drug administration
      atipamezole was administered at a dose of approximately 240 micrograms/kg.
      Recovery time was taken as the time from administration of the atipamezole until
      the time that the bear was sitting in the trap. Recovery occurred in 6.0 +/- 4.1
      min. MZT produced rapid, reliable immobilization in black bears with minimal
      adverse physiological effects. Immobilization, produced by this combination, was
      readily reversible with atipamezole.

PMID- 9249711
TI  - Detection of canine parvovirus in wolves from Italy.
AB  - One hundred fifteen samples of wolf (Canis lupus) feces were collected during
      1994 to 1995 from four free-living populations of the north central Apennines
      Mountains, Italy. The samples were tested for canine parvovirus by antigen
      capture enzyme-linked immunosorbent assay (ELISA), hemagglutination, and virus
      isolation. Four of these samples were positive by virus isolation as confirmed by
      electron microscopy. All positive samples were from Casentino Park in Tuscany.
      This is the first definitive observation of canine parvovirus in wolves from
      Europe.

PMID- 9249712
TI  - Isolation and characterization of Aujeszky's disease virus in captive brown bears
      from Italy.
AB  - An epizootic of Aujeszky's disease (pseudorabies) in four captive European brown
      bears (Ursus arctos) in November 1994, in the Val di Non, Trentino Region, Italy,
      was linked to consumption of raw pork. Affected animals had severe pruritus
      resulting in self-mutilation, and all four died within 24 hr after onset of
      clinical signs. Aujeszky's disease virus was isolated on first passage from the
      brain and was characterized by means of restriction endonuclease analysis. Based
      on these data, we believe that bears are extremely susceptible to the disease,
      and that wildlife managers should consider pseudorabies as a potential risk for
      the captive and wild bear populations.

PMID- 9249713
TI  - Radiometric culture of Mycobacterium avium paratuberculosis from the feces of
      tule elk.
AB  - To determine if Mycobacterium avium paratuberculosis has persisted in tule elk
      (Cervus elaphus nannodes) at Point Reyes National Seashore (California, USA), 100
      fresh fecal samples were collected. Feces were cultured on a modified BACTEC 12B
      radiometric medium for detection of M. avium paratuberculosis. Four samples,
      coming from two separate groups of elk tested positive for M. avium
      paratuberculosis. Thus, a noninvasive technique was used to document the
      continued presence of M. avium paratuberculosis in elk at Point Reyes National
      Seashore. These findings document persistence of this organism for a period of at
      least 13 yr in a free ranging herd of elk, with a 6 yr absence of observed
      clinical signs.

PMID- 9249714
TI  - Blood parasites of passerine birds from central Spain.
AB  - Sixteen species of passerine birds captured during a 2.5 yr period in Central
      Spain were examined for hematozoa. Haemoproteus spp., Leucocytozoon spp.,
      Trypanosoma spp., Plasmodium spp., and microfilariae were observed. The most
      prevalent species were in the genus Leucocytozoon. The majority of the records
      are new for Spain and some represent new host records. More than one-half of the
      birds examined were infected with at least one parasite species. These records
      are similar to those reported from other areas in northern Europe and the Iberian
      Peninsula.

PMID- 9249715
TI  - Hematozoa in two populations of the threatened red-billed chough in Spain.
AB  - The prevalence of hematozoa in two populations of red-billed choughs (Pyrrhocorax
      pyrrhocorax) was sampled in 1992 and 1994 in Spain. Two blood parasites infected
      red-billed choughs. A species of Plasmodium, possibly Plasmodium relictum, and
      the piroplasm Babesia frugilegica, are described for the first time from this
      host. Low prevalence (1/178, < 1%) of hematozoa in these populations, was
      evidence for a lack of effects of blood parasites on the life history and
      conservation of this threatened species in at least the two populations studied.

PMID- 9249716
TI  - Giardiasis in ringed seals from the western arctic.
AB  - Sixteen beluga whales (Delphinapterus leucas) and fifteen ringed seals (Phoca
      hispida) from the western arctic region of Canada were examined for giardiasis
      and cryptosporidiosis. Intestinal contents from the rectum and colon were
      collected from animals slaughtered by Inuit hunters. A fluorescent monoclonal
      antibody identified Giardia sp. cysts in three of 15 (20%) seals. Thus, ringed
      seals are implicated as a potential reservoir for this zoonosis in the arctic.

PMID- 9249717
TI  - Serologic survey for toxoplasmosis in river otters.
AB  - The prevalence of antibody titers to Toxoplasma gondii in river otters (Lutra
      canadensis) from eastern North Carolina (USA) was investigated in a cross
      sectional study. Sera from 103 live trapped river otters were tested for
      antibodies to T. gondii using a commercially available latex agglutination kit.
      Forty-six (45%) of the sera were positive with titers ranging from 1:16 to >
      1:2,048. Adult otters (n = 78) had a seroprevalence of 47% and juvenile otters (n
      = 25) had a seroprevalence of 39%. Significant differences were not found between
      the sexes within either maturity class. The high prevalence of antibodies to T.
      gondii indicates that many animals in this population were exposed to the
      organism. This suggests handling of otters may be a zoonotic concern for fur
      trappers.

PMID- 9249718
TI  - Baylisascariasis in raccoons from southern coastal Texas.
AB  - Two hundred and two Baylisascaris procyonis were collected from 23 (70%) of 33
      raccoons (Procyon lotor) at three localities in southern coastal Texas (USA).
      Abundances of B. procyonis were similar among collection localities. The presence
      of B. procyonis in Texas is confirmed, and this record considerably extends the
      potential range of baylisascariasis larval migrans in North America.

PMID- 9249719
TI  - Haemonchosis in Spanish ibex.
AB  - Two cases of haemonchosis occurred in the Spanish ibex (Capra pyrenaica)
      population of the National Hunting Reserve of Tortosa and Beseit, northeastern
      Spain, in July 1992 and May 1993. The animals were cachectic and recumbent and
      had an acute hemorrhagic, macrocytic and hypochromic anemia; which was related to
      a high infection of 2,016 and 1,863 Haemonchus contortus, respectively, in the
      abomasum of the animals.

PMID- 9249720
TI  - Helminths of wintering geese in Texas.
AB  - Ten Canada geese (Branta canadensis), 24 snow geese (Chen caerulescens) and 22
      white-fronted geese (Anser albifrons) from coastal Texas (USA) were examined for
      helminths. Three cestode, seven nematode, and three trematode species were
      collected. Gizzard nematodes (Amidostomum anseris, A. spatulatum and
      Epomidiostomum crami) infected 53 of 54 birds. Gross lesions were not attributed
      to helminth infections and the host population does not appear to be impaired by
      them.

PMID- 9249721
TI  - Contact transmission of psoroptic mange from bighorn to Stone sheep.
AB  - Psoroptes sp. mites and tan crusty lesions were detected in the ears of a captive
      Stone sheep (Ovis dalli stonei) in April 1996, after contact with infected
      captive Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Psoroptes spp.
      have not been detected in free-ranging ungulates in Canada or Alaska (USA). This
      is the first report of Psoroptes sp. in Stone sheep, indicating their
      susceptibility to infection.

PMID- 9249722
TI  - Lymphosarcoma in a brook trout.
AB  - A 2-yr-old female brook trout, Salvelinus fontinalis, maintained at a state fish
      hatchery in New York (USA) was culled from the breeding stock. At necropsy, it
      had a markedly enlarged kidney. On histopathological examination, lymphoblastic
      lymphoma was diagnosed in several organs including kidney, dorsal musculature,
      intestines, liver, gill, pseudobranch and ovary. Origin of the tumor was
      uncertain, although renal involvement could have been the primary site of
      development.

PMID- 9249723
TI  - Abnormal antler growth associated with testicular hypogonadism in red deer.
AB  - A wild 5-yr-old red deer (Cervus elaphus) was eulled from a privately owned herd
      because of deformed antlers, retained velvet and bilateral symmetrical testicular
      hypogonadism. The clinical and pathological changes seen in this deer were most
      consistent with congenital hypoplasia, but testicular atrophy was an alternative
      possibility for the etiology of their condition.

PMID- 9249724
TI  - Mortality of captive British wartbiter crickets: implications for reintroduction
      programs.
AB  - A fungal infection was identified as the cause of a high mortality rate of
      captive wartbiter cricket (Decticus verrucivorus) nymphs at the London Zoo
      (United Kingdom) in 1994. This species is threatened with extinction in the
      United Kingdom and the animals concerned were part of a captive breeding and
      reintroduction program. Following these findings, reintroductions were postponed
      and release sites were used only where there were no extant wartbiter crickets.

PMID- 9249726
TI  - Clinical and histological features of cytomegalovirus hepatitis in previously
      healthy adults.
AB  - It is well known that cytomegalovirus infection is often accompanied by
      hepatitis, but there have been few comparative studies with respect to clinical
      features of cytomegalovirus-associated hepatitis and other acute viral
      hepatitides. In the present study, clinical and pathological features of 11 acute
      sporadic cytomegalovirus hepatitis infections in previously healthy adults were
      compared with those of 45 acute sporadic viral hepatitis, including type A, type
      B and type C. As a result, the characteristics of cytomegalovirus hepatitis were
      a long-lasting fever, splenomegaly, atypical lymphocytosis, a mild
      transaminasemia, a low ratio of alanine aminotransferase level to lactate
      dehydrogenase level, and mild hepatic histopathological changes.

PMID- 9249725
TI  - Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at
      early stages between a benign and a progressive course: a prospective study on
      200 patients followed for 10 years.
AB  - In recent retrospective studies, it was shown that subtypes of antimitochondrial
      antibodies (AMA) can help to discriminate between a benign [only anti-M9 and/or
      anti-M2 positive by enzyme-linked immunosorbent assay (ELISA)] and a rather
      progressive course (anti-M2, -M4 and/or -M8 positive). According to different
      constellations of these AMA subspecificities in ELISA and complement fixation
      test (CFT), four AMA profiles (A-D) were defined. In 1984 we started a
      prospective study based on 200 PBC patients with known AMA profiles in order to
      correlate the antibody pattern with the clinical outcome. Progression was defined
      primarily as the necessity of liver transplantation and death due to hepatic
      failure or variceal bleeding. At entry, 18 (9%) of the 200 patients had AMA
      profile A (only anti-M9), 57 (29%) profile B (only anti-M2 with or without anti
      M9), 74 (37%) profile C (anti-M2 in association with anti-M4/-M8 by ELISA), and
      51 (26%) profile D (anti-M2/-M4/-M8 by ELISA and CFT). At the beginning of the
      study, 177 patients had PBC stage I/II. During the observation period of ten
      years, ten patients died and in 18 orthotopic liver transplantation (OLT) was
      performed; all these patients belonged to profile C/D. Furthermore, 44% of the
      patients with profile C and 31% of the patients with profile D progressed to late
      stages, as defined by histology and clinical manifestations such as portal
      hypertension and increase of bilirubin, while only one of the patients with
      profile B and none of the profile A-patients developed late stage PBC. A
      significant increase of bilirubin was observed only in C/D-patients. AMA profiles
      did not change during the follow-up. In conclusion, AMA profiles discriminate
      between a benign and a progressive course of PBC already at early stages.

PMID- 9249727
TI  - Virological characterization and liver histology in HCV positive subjects with
      normal and elevated ALT levels.
AB  - We analyzed HCV genotype and RNA titer in 36 chronically infected subjects, 20
      with persistently normal or near-normal alanine aminotransferase (ALT) activity
      and 16 with raised ALT activity. All subjects underwent liver biopsy and
      evaluation of the histological activity index (HAI) by both Knodell's and Ishak's
      scoring systems. Genotype 2 was detected in most subjects with normal ALT
      activity, whereas genotype 1 was more frequent among subjects with raised ALT
      activity. HCV-RNA titer was higher in subjects with increased ALT. Histological
      evidence of chronic hepatitis was documented in all cases, but higher scores for
      grading and for staging were associated with increased ALT activity. HCV genotype
      had no statistical relationship with RNA titer or with liver histology. In
      logistic regression analysis, viral genotype, RNA titer or with liver
      histological scores for grading and staging were correlated independently with
      the ALT profile. The evidence of chronic hepatitis in all subjects with
      persistently normal ALT activity suggests that healthy HCV carriage is a rare
      event.

PMID- 9249728
TI  - Allopurinol improves scavenging ability of the liver after ischemia/reperfusion
      injury.
AB  - Deterioration of energy metabolism and oxidative stress represent fundamental
      mechanisms in ischemia and reperfusion injury. In a normothermic
      ischemia/reperfusion rat model, we investigated whether allopurinol (ALL) may
      improve the scavenging ability of the liver after ischemia. ALL was given prior
      to ischemia and reperfusion (concentration 100 or 50 mg/kg) and controls were
      given a placebo. After a basal period of 30 min, 1 h normothermic ischemia was
      induced in the median and left liver lobes followed by 24 h observation. The
      overall liver function was assessed by bile secretion, and free oxygen production
      was assessed by glutathione efflux into bile during the first 60 min of
      reperfusion and at 24 h. Allopurinol (concentration 100 mg/kg) protected
      hepatocyte function as bile flow improved significantly in this group after 1 and
      24 h of reperfusion compared with that of controls. Oxidative stress was also
      significantly attenuated in this group, as efflux of glutathione into bile was
      significantly higher in the ALL group (100 mg/kg) after 24 h but not after 1 h of
      reperfusion compared with that of controls. All given in a concentration 50 mg/kg
      had some, but a non-significant, effect. We conclude that biliary glutathione is
      an important marker of oxidative stress and may reflect the scavenging ability of
      the liver after ischemic injury. Significant correlation of bile flow with
      biliary glutathione during reperfusion indicates that oxidative stress is an
      important mechanism attenuating liver function after ischemia/reperfusion injury.

PMID- 9249730
TI  - Lamellar fibrosis in the fibrolamellar variant of hepatocellular carcinoma: a
      role for transforming growth factor beta.
AB  - Transforming growth factor-beta (TGF-beta) is a pluripotent regulatory molecule,
      found in at least five different isoforms. It is produced in many different
      organs. In the liver, TGF-beta is expressed in non-parenchymal cells, but not in
      hepatocytes. This growth factor is known to induce fibrosis in the course of a
      variety of pathologic processes. Recently, TGF-beta has also been identified in
      hepatocellular carcinoma (HCC) cells, and the suggestion has been made that this
      growth factor may play a role in hepatocarcinogenesis. In this study, we report
      the findings of immunohistochemical stains for TGF-beta, performed on paraffin
      sections of 14 human HCCs of the usual type and 11 examples of the fibrolamellar
      variant (FLC). TGF-beta was detected in tumor cells of 3 HCCs (21%) and 9 FLCs
      (82%). Compared with the HCCs, the FLCs displayed a more diffuse and intense
      staining pattern for TGF-beta. Our findings suggest that lamellar fibrosis, which
      is a histologic hallmark of FLC, may be due to the action of TGF-beta produced by
      tumor cells.

PMID- 9249729
TI  - The relationship of histology to genotype in chronic HCV infection.
AB  - The histological description of chronic hepatitis is undergoing considerable
      change at present. It has become important to define chronic hepatitis
      aetiologically and then define levels of necro-inflammatory change (grade) and
      fibrosis (stage). The aim of this study was to compare the ability of different
      histological scoring systems to detect differences in the pathological changes
      associated with infection with the different HCV genotypes that are known to have
      different natural histories. The histological appearances of liver biopsies from
      29 HCV infected patients were compared by the Knodell histological activity index
      (HAI), modified histological activity index and the Scheuer histological scoring
      system. HCV genotyping was performed for each patient by sequence analysis of the
      5' non-coding region. The histological appearances from HCV 1 infected patients
      showed a tendency towards more active necro-inflammatory changes when compared
      with those from HCV 2 or 3 infected patients. The levels of fibrosis were similar
      for all genotypes. The modified HAI and Scheuer scoring systems detected
      differences, not revealed by the Knodell system, in the types of inflammatory
      pathology produced by the different genotypes of HCV. In particular these scoring
      systems noted significant differences in the component scores of inflammation, in
      addition to the total inflammatory scores. In conclusion, the recently introduced
      scoring systems were able to detect differences in liver pathology produced by
      infection of similar duration with different viral genotypes. As genotype is
      considered an important determinant of disease progression and response to anti
      viral therapy, it is likely that those scoring systems correlating with genotype
      will yield more useful histological information than those that do not.

PMID- 9249731
TI  - Modulation of Kupffer cell and peripheral blood monocyte activity by in vivo
      treatment of rats with all-trans-retinol.
AB  - Previous studies have shown that large doses of vitamin A potentiate chemical
      induced liver injury and that the Kupffer cell is directly involved in this
      potentiation. Therefore, these studies were designed to determine if Kupffer
      cells isolated from vitamin A treated male Sprague-Dawley rats (75 mg/kg/day for
      3-7 days as all- trans-retinol) had altered activity and function. Respiratory
      activity of Kupffer cells isolated from rats treated with vitamin A for 3 to 7
      days markedly increased. Similarly, phagocytic activity was significantly
      elevated (up to 9-fold) after exposure to vitamin A for 3 to 7 days. Production
      of reactive oxygen species, measured by luminol-enhanced chemiluminescence of
      Kupffer cells isolated after 7 days of vitamin A exposure, was significantly
      higher than that of control cells when stimulated with opsonized zymosan. Also,
      the release of superoxide anion by individual Kupffer cells isolated from vitamin
      A treated rats was nearly three times greater than that of control cells. Basal
      production of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2)
      production were significantly elevated in Kupffer cells isolated from rats
      treated with vitamin A. Lastly, peripheral blood monocytes (PBMC) isolated from
      rats treated with vitamin A for 7 days had a significantly greater respiratory
      activity, as well as TNF-alpha and PGE2 production, than PBMC isolated from
      control rats. Our data suggest that large doses of vitamin A enhance both Kupffer
      cell and PBMC function. Upregulation of the activity by these phagocytic cells
      may play a role in the vitamin A potentiation of chemical-induced liver injury.

PMID- 9249732
TI  - Nitrofurantoin toxicity to both liver and lungs.

PMID- 9249733
TI  - Preparation of brain slices.

PMID- 9249734
TI  - Preparation of organotypic hippocampal slice cultures using the membrane filter
      method.

PMID- 9249735
TI  - The preparation and use of brain slices and dissociated neurons for patch-clamp
      studies of neurotransmitter action.

PMID- 9249736
TI  - Synaptosomes. A model system to study release of multiple classes of
      neurotransmitters.

PMID- 9249737
TI  - Synaptoneurosomes. A preparation for studying subhippocampal GABAA receptor
      activity.

PMID- 9249738
TI  - Preparation of synaptosomal plasma membranes by subcellular fractionation.

PMID- 9249739
TI  - Detection of neuropeptides by immunocytochemistry.

PMID- 9249740
TI  - Immunocytochemical detection of amino acid neurotransmitters in paraformaldehyde
      fixed tissues.

PMID- 9249741
TI  - cGMP-immunocytochemistry.

PMID- 9249742
TI  - Microwave antigen retrieval in formaldehyde-fixed human brain tissue.

PMID- 9249743
TI  - Localization of nitric oxide synthase using NADPH diaphorase histochemistry.

PMID- 9249744
TI  - In situ hybridization to determine the expression of peptide neurotransmitters.

PMID- 9249745
TI  - Quantitative in situ hybridization histochemistry.

PMID- 9249746
TI  - Microbore liquid chromatography analysis of monoamine transmitters.

PMID- 9249747
TI  - Microbore liquid chromatography analysis of amino acid transmitters.

PMID- 9249748
TI  - HPLC methods to isolate peptide neurotransmitters.

PMID- 9249749
TI  - Neuropeptide expression patterns as determined by matrix-assisted laser
      desorption ionization mass spectrometry.

PMID- 9249750
TI  - GC/MS determination of biogenic amines in insect neurons.

PMID- 9249752
TI  - In vivo detection of neurotransmitters with fast cyclic voltammetry.

PMID- 9249751
TI  - Monitoring amino acid neurotransmitter release in the brain by in vivo
      microdialysis.

PMID- 9249753
TI  - Novel oxidatively removable protecting groups and linkers for solid-phase
      synthesis of oligosaccharides.
AB  - Several new para-substituted benzyl- or phenyl-type protecting groups and their
      application to linkers for solid-phase synthesis are described. p-Acylaminobenzyl
      groups have higher acid stability than the p-methoxybenzyl (MPM) group, but are
      readily cleaved with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The p
      azidobenzyl (Azb) group also has higher acid stability than the MPM group and can
      be removed much faster than the MPM group by DDQ oxidation after conversion of
      the azide group into the corresponding iminophosphorane. The acid stability of
      the p-azido-m-chlorobenzyl group (Cl-Azb) is higher than that of the Azb group.
      The former can be readily removed by DDQ oxidation after conversion of the azide
      group into the iminophosphorane. The p-acylaminophenyl glycoside linker can be
      readily obtained from p-nitrophenyl glycoside and can be readily cleaved by
      ammonium cerium(IV) nitrate (CAN) oxidation. This type of linker should be useful
      not only for the solid-phase synthesis of oligosaccharides but also for general
      solid-phase synthesis.

PMID- 9249754
TI  - Multidimensional chromatography coupled with mass spectrometry for target-based
      screening.
AB  - The synthesis of structural analogs and the process of drug discovery have
      evolved dramatically through recent advances in solid-phase synthesis reagents
      and automated screening systems. As molecular diversity strategies emerge, the
      need for automated target-based selection of lead candidates becomes equally
      important. Multidimensional automated chromatographic techniques coupled to
      electrospray ionization mass spectrometry facilitate the selection process and
      provide maximum characterization information in a single screening run. The
      capture of tightly bound affinity leads by target biomolecules, followed by
      subsequent release and high-resolution separation with sensitive detection,
      significantly reduces the time required to identify and characterize lead
      compounds. This automated multidimensional chromatographic approach coupled with
      mass spectrometry, Selectronics, was used with several organic and natural
      libraries to demonstrate an automated target-based screening technique to select
      for high-affinity binders as potential lead compounds.

PMID- 9249755
TI  - Automated chemical synthesis: from resins to instruments.
AB  - Solid-phase organic synthesis is now a prevalent activity in drug discovery. In
      keeping with this keen interest is the need to develop reliable automated
      synthesis instrumentation as well as polymeric supports and linkers suitable for
      the full range of organic synthesis applications. In this paper, we review our
      activities in the development of new and enabling tools for automated chemical
      synthesis, including the following: (i) new solid supports such as ArgoGel (PS
      PEG-based) and Argo-X203 (PS-based); and (ii) the Nautilus 2400 system, a fully
      closed and inert automated chemistry development workstation. Selected chemistry
      optimization and synthesis examples performed on the Nautilus and new solid
      supports will be described.

PMID- 9249756
TI  - Dipolar cycloadditions in solid-phase organic synthesis (SPOS).
AB  - We present a concise review of polymer-supported 1,3-dipolar cycloaddition
      reactions. Nitrile oxide and azomethine ylides constitute the two types of 1,3
      dipoles which have been used in conjunction with solid-phase organic synthesis.
      These cycloaddition reactions on solid phase are generally of equal or greater
      efficiency than the analogous solution-phase reactions.

PMID- 9249757
TI  - Future pathways for combinatorial chemistry.
AB  - Investment in combinatorial chemistry (combichem) in the pharmaceutical industry
      is being driven by the need for increased efficiency. Results from pioneers in
      the field have demonstrated where mixture or discrete compound synthesis is
      useful, and what mixture sizes and compound concentrations are appropriate. To
      make the techniques of combichem of general utility in drug discovery, a broad
      range of advances is still required. Conversion of organic chemistry to solid
      phase conditions is key, as are developments in linkers and resins. Library
      design methodology requires further development. Combinatorial biosynthesis of
      focused libraries of natural products holds great promise for capitalising on
      hardwon natural product leads. Miniaturisation of screens is required to reduce
      the cost of screening combinatorial libraries. Developments in the processes
      preceding and following synthesis are required to enable the flow of increased
      numbers of compounds without new bottlenecks developing. The impact of
      combinatorial chemistry will be greatly enhanced by synergy with ongoing parallel
      developments in genetic technologies, screening technologies and bioinformatics.

PMID- 9249758
TI  - Discovery of enzyme inhibitors through combinatorial chemistry.
AB  - This review serves to highlight the recent examples of combinatoric methodology
      as applied to the discovery and optimization of enzyme inhibitors. Early research
      efforts focused on the identification of polypeptides from libraries as
      inhibitors of proteases. As solution- and solid-phase chemistries gain in
      sophistication, libraries containing less peptidic structural motifs have been
      created. A recurring design stratagem relies on the synthesis of libraries
      incorporating pharmacophores with known affinity for the target enzyme. Screening
      of these structure-based libraries has led to the discovery of small-molecule
      inhibitors of both proteolytic and non-proteolytic enzymes alike. Two tables are
      provided listing the enzyme targeted libraries through 1996. A name, generic
      structure and size is given for each library citation, accompanied by the enzyme
      screen and the structure and potency of the most active library member.

PMID- 9249759
TI  - Chemokines and their receptors in leukocyte trafficking and renal inflammation.

PMID- 9249760
TI  - Advanced oxidation protein products: novel uraemic toxins and pro-inflammatory
      mediators in chronic renal failure?

PMID- 9249761
TI  - Tacrolimus in renal transplantation.

PMID- 9249762
TI  - Diabetic nephropathy in the NIDDM patient on the interface between diabetology
      and nephrology. What do we have to improve?

PMID- 9249763
TI  - There is room for improvement of preterminal care in diabetic patients with end
      stage renal failure--the epidemiological evidence in Germany.

PMID- 9249764
TI  - Serum leptin concentrations correlate to plasma insulin concentrations
      independent of body fat content in chronic renal failure.
AB  - BACKGROUND: The ob gene product leptin is secreted by fat cells and reflects the
      content of fat in the body. Leptin and insulin concentrations as well as body
      weight are interrelated and a direct correlation has been found between these
      concentrations in humans with normal renal function. Markedly elevated serum
      leptin concentrations have recently been reported in patients with chronic renal
      failure (CRF). The aim of the present study was to investigate the relation
      between serum leptin and plasma insulin in patients with advanced CRF. METHODS:
      Serum leptin, plasma insulin, as well as body fat content (determined with dual
      energy X-ray absorptiometry) were determined in a cohort of 46 patients (mean age
      54 +/- 2 years) with advanced CRF (creatinine clearance 8 +/- 1 ml/min). RESULTS:
      In 23 CRF patients with plasma insulin below the median value (14 mU/l), serum
      leptin concentrations were no higher than in healthy controls (8.0 +/- 1.2 vs 8.4
      +/- 0.9 ng/ml). However, in CRF patients with plasma insulin > 14 mU/l (n = 23)
      the serum leptin concentrations were much higher (38.2 +/- 11.0 ng/ml; P <
      0.0001). In CRF patients, serum leptin (normalized for the per cent body fat
      content) correlated significantly (r = 0.64; P < 0.0001) with plasma insulin
      concentrations. However, the increase in plasma insulin was blunted in patients
      with very high serum leptin concentrations in relation to the per cent body fat
      content. CONCLUSIONS: The present results demonstrate that serum leptin
      concentrations are markedly elevated in CRF patients with higher plasma insulin
      than in those with lower plasma insulin concentrations. This suggests that
      insulin resistance and hyperinsulinaemia contribute to elevated serum leptin
      concentrations in CRF. The present results also demonstrate that, when
      circulating serum leptin concentrations are much higher in relation to the per
      cent body fat content, no additional increase in plasma insulin occurs. This
      latter observation suggests that the secretion of insulin by the pancreas is
      lower in hyperleptinaemic patients. Consequently, extremely elevated serum leptin
      may play a role in reducing glucose-stimulated insulin secretion and glucose
      intolerance in CRF.

PMID- 9249765
TI  - Hepatitis G virus infection in haemodialysed patients: epidemiology and clinical
      relevance.
AB  - BACKGROUND: The prevalence, incidence, risk factors, and clinical impact of
      infection by the recently discovered hepatitis G virus (HGV) in haemodialysed
      (HD) patients, are poorly defined. METHODS: All 119 HD patients from two Belgian
      units selected for their different hepatitis C virus (HCV) prevalences (A: 19.2%,
      B: 3.4%) were tested for the presence of HGV-RNA, using the reverse transcriptase
      polymerase chain reaction (RT-PCR) and primers from the 5'-NC and NS 5a genome
      regions. The results of anti-HCV antibodies and alamine aminotransferase levels
      (ALT) at the time of RT-PCR, number of transfusions from the onset of HD, and
      time on HD were retrieved from the medical charts. Forty patients were retested
      by RT-PCR 3-64 months later. RESULTS: HGV-RNA was detected with both sets of
      primers in 11/78 patients (14.1%) from centre A and 8/41 patients (19.5%) from
      centre B, for an average prevalence of 16%. One patient was indeterminate
      (positive with one set of primers). The presence of HGV-RNA correlated neither
      with time on HD (P = 0.18), nor with the number of transfusions on HD (P = 0.14).
      It was associated with the presence of anti-HCV antibodies in centre A (P < 0.01)
      but not B (P > 0.5). Twenty-seven initially negative (-) patients (A: n = 18; B:
      n = 9) were retested: two became positive (+) both in the absence of transfusions
      for years, giving a yearly incidence of 1.7%. The 13 initially HGV-RNA (+)
      patients remained so over time (33 patient-years). The presence of HGV-RNA alone
      does not increase significantly the ALT level, in contrast to the strong
      influence of HCV. CONCLUSION: The prevalence and yearly incidence of HGV
      infection are 16% and 1.7%, respectively, in our HD patients. Neither the number
      of transfusions on HD nor the time on HD are significant risk factors. Although
      mixed HCV/HGV infections indicate common risks, the prevalence of HCV in a
      particular setting does not predict prevalence of HGV. As new infections are
      detected in the absence of blood transfusions, HGV may be another marker of
      nosocomial viral transmission. Once acquired, the infection persists for many
      years in HD patients.

PMID- 9249766
TI  - Lipoprotein(a) induces glomerular superoxide anion production.
AB  - BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to accelerate glomerular injury
      in various forms of renal disease. Several tissue culture studies suggested that
      biological effects of Lp(a) are inhibitable by oxygen radical scavengers. Since
      reactive oxygen metabolites (ROM) are important mediators of renal disease, we
      studied the effects of native and oxidized Lp(a) on generation of the ROM
      superoxide anion in isolated glomeruli and compared them with the effects of
      native (nLDL) and oxidized LDL cholesterol (oxLDL). METHODS: The effect of native
      and oxidized Lp(a) and LDL on ROM production in isolated rat glomeruli was
      investigated with a lucigenin chemiluminescence assay. RESULTS: Native Lp(a)
      caused a moderate, dose dependent stimulation of glomerular ROM production:
      Maximum ROM production to 159 +/- 9% of control glomeruli was induced by nLp(a)
      20 micrograms/ml. Lp(a)-induced chemiluminescence was completely inhibited by the
      cell permeable oxygen radical scavenger Tiron (10 Mm). Oxidized Lp(a) (20
      micrograms/ml) caused a more pronounced stimulation of ROM production to 204 +/-
      12% of control values. Interestingly, only oxLDL, but not nLDL had a significant
      effect on glomerular ROM production (ox LDL 50 micrograms/ml: 192 +/- 19% of
      control). Lp(a) stimulated ROM production was completely inhibited by the protein
      kinase C inhibitor bis- indolyl malemide (BIM): BIM 10(-6) M inhibited 52 +/- 3%,
      BIM 10(-5) M inhibited 94 +/- 5% of Lp(a)-induced ROM production. ROM production
      was also inhibited, when intracellular CAMP levels were elevated by forskolin.
      CONCLUSION: Lp(a) and oxLp(a) induce the activation of ROM in glomeruli by a
      pathway that is sensitive to inhibition of protein kinase C and elevation of
      intracellular CAMP levels.

PMID- 9249767
TI  - Uptake and metabolism of lipoproteins from patients with diabetes mellitus type
      II by glomerular epithelial cells.
AB  - BACKGROUND: Recent studies suggest that dyslipidaemia accelerates the progression
      of diabetic nephropathy, but the various pathomechanisms underlying such
      abnormalities are not completely delineated. METHODS: We isolated, radiolabelled,
      and characterized very-low-density lipoproteins (VLDL) and low-density
      lipoproteins (LDL) from eight diabetic patients with moderate impairment of renal
      function and dyslipidaemia and studied their interaction with LDL receptors in
      human glomerular epithelial cells. RESULTS: While diabetic VLDL showed no
      compositional changes, LDL particles contained a higher proportion of
      triglycerides at the expense of cholesterol in comparison with healthy controls.
      Despite differences in composition, both VLDL and LDL from patients exhibited
      reduced receptor affinity and cellular uptake capacity by glomerular epithelial
      cells. Since LDL composition was altered intracellular cholesterol homeostasis
      was investigated. Due to reduced cholesterol content and lower uptake capacity,
      diabetic LDL were less effective in suppressing intracellular sterol synthesis
      and in activating acylcholesterol acyltransferase than LDL from controls.
      Electrophoretic mobility of apoB from diabetic patients was enhanced as compared
      to controls, most probably due to the higher degree of glycation (17 + 1.7 versus
      11 + 1%, P < 0.05) but not to oxidation (TBARS 0.5 + 0.2 versus 0.2 + 0.1
      mumol/1). Oxidized LDL was not taken up in significant amounts, indicating no
      scavenger receptor activity in glomerular epithelial cells. CONCLUSION: The
      receptor-specific uptake of diabetic VLDL and LDL by glomerular epithelial cells
      is impaired. Compositional changes of the LDL particle and glycation of the
      protein moiety may contribute to altered glomerular uptake. However, glycation of
      the protein moiety may be superior to compositional changes. Because glomerular
      structures like mesangial matrix and endothelial cells are known for preferential
      binding of modified lipoproteins, further studies are required to elucidate their
      potential role in the progression of diabetic glomerulosclerosis.

PMID- 9249768
TI  - Upregulated renal tubular CD44, hyaluronan, and osteopontin in kdkd mice with
      interstitial nephritis.
AB  - BACKGROUND: The hyaluronan (HA) receptor CD44 is upregulated on parenchymal cells
      in various inflammatory lesions and could play a role in immune injury. The
      purpose of the present study was to examine CD44 and its ligands HA and
      osteopontin (Opn) in a murine model of tubulointerstitial nephritis (TIN).
      METHODS: The expression of CD44 was investigated by immunofluorescence staining
      and RNA analysis in kidneys of kdkd mice with autoimmune TIN. The CD44 expression
      was then correlated with the location of its ligands HA and Opn. RESULTS: CD44 is
      expressed de novo by tubular epithelial cells (TEC) in areas of tubular injury in
      kdkd kidneys, but not in normal control kidneys. CD44 positive lymphocytes and
      macrophages also infiltrate the kidney to kdkd mice. RT-PCR and Southern blot
      analysis demonstrate that transcripts encoding standard and variant forms of CD44
      are increased in kdkd mice with TIN. In parallel the CD44 ligand HA also
      accumulates in kdkd kidneys in the interstitial space, particularly in cortical
      areas of tubular injury. Furthermore, the expression of the chemotactic protein
      Open is enhanced in kdkd kidney, predominantly in areas of tubular injury. Opn
      mRNA expression also increases markedly in kdkd kidneys compared with normal
      kidneys, and correlates with disease severity. CONCLUSIONS: Prominent CD44
      expression by TEC in areas of tubulointerstitial lesions is a characteristic
      feature of kdkd mice. The de novo appearance of CD44 on injured TEC might allow
      interaction with the ligands HA and Opn in vivo. Interaction of CD44 with these
      ligands could participate in the tubulointerstitial inflammatory response in kdkd
      mice.

PMID- 9249769
TI  - Oral-facial-digital syndrome type 1 is another dominant polycystic kidney
      disease: clinical, radiological and histopathological features of a new kindred.
AB  - BACKGROUND: Oral-facial-digital syndrome type 1 (OFD1) is a rare disorder
      comprising malformations of the face, oral cavity, hands, and feet. Polycystic
      kidney disease (PKD) is a more recently recognized feature of the syndrome.
      SUBJECTS AND METHODS: We now report on the clinical, radiological and
      histopathological features of an OFD1 and PKD kindred with five affected members
      in three subsequent generations. RESULTS: All patients were female and had
      accompanying PKD as assessed by ultrasound scans. The plasma creatinine was
      normal in three, but PKD caused end-stage renal failure in two of these
      individuals in the second and fifth decades. A histochemical analysis of renal
      tissue from one affected member of this kindred demonstrated a predominantly
      glomerulocystic kidney disease with a minor population of cysts derived from
      distal tubules as assessed by staining with Arachis hypogaea lectin. Cyst
      epithelia had a high level of mitosis as assessed by staining with antisera to
      proliferating cell nuclear antigen, and distal cysts overexpressed PAX2 protein,
      a potentially oncogenic transcription factor. We detected multiple pancreatic
      cysts in one member affected by OFD1 although there were no symptoms of
      pancreatic disease; this constitutes a novel radiological feature of the
      syndrome. CONCLUSIONS: This kindred illustrates the inheritance pattern of OFD1
      and its accompanying PKD. Although the renal disease superficially resembles
      ADPKD with macroscopic cysts and a dominant inheritance pattern, histology shows
      a predominance of glomerular cysts and the syndrome is X-linked, with affected
      males dying before birth. The recognition of the accompanying dysmorphic features
      is the key to a diagnosis of OFD1 in a female child or adult who presents with
      PKD.

PMID- 9249770
TI  - Metabolic evaluation of patients with recurrent idiopathic calcium
      nephrolithiasis.
AB  - BACKGROUND: Metabolic evaluation in recurrent idiopathic calcium renal stone
      formers (RCSF) was analysed with respect to the following questions: (1) do three
      24-h urines provide more diagnostic accuracy in the metabolic evaluation of RCSF
      than 1 or 2 urines?; (2) does time after stone event influence the diagnostic
      yield?; (3) is urine composition at weekends different from that at mid-week?;
      (4) what are the prevalences of the most important risk factors (RF) of
      idiopathic calcium nephrolithiasis, i.e. low volume (LV), hypercalciuria (HC),
      hyperoxaluria (HO), hyperuricosuria (HU), hypocitraturia (Hypo-Cit), and
      hypomagnesiuria (Hypo-Mg)?; and (5) do male RCSF differ from females with respect
      to urinary RFs? METHODS: Seventy-five RCSF (59 men, 16 women) collected three 24
      h urines (U1-3) while on free-choice diet. To account for possible variations in
      lifestyle and diet, U1 and U3 had to be collected midweek and U2 at a weekend.
      RESULTS: When considering all three urines together (U1 + U2 + U3), the number of
      RF abnormalities/patient was 2.8 +/- 0.1, higher than numbers of any combination
      of two urines or of any single urine (P = 0.0001 for all comparisons). The number
      of RF abnormalities also rose with time after stone event, from 0.8 +/- 0.1
      (range 0-4) in U1 to 1.1 +/- 0.1 (range 0-4) in U3 (P = 0.011 vs U1). Whereas all
      other RF did not change between collections, urine volume was lower in U2 (1793
      +/- 90 ml) than in U1 (2071 +/- 97 ml, P = 0.0001 vs U2) and U3 (1946 +/- 97 ml,
      P = 0.046 vs U2). At least 1 abnormality was found in 85.3% of all RCSF, and
      multiple abnormalities occurred in 47%. The most frequent RF was HC (39%),
      followed by HO and LV (32% each), Hypo-Cit (29%), HU (23%) and Hypo-Mg (19%).
      Males more often had Hypo-Cit (P < 0.001) and Hypo-Mg (P < 0.01) than females,
      whereas HO was more frequent in female RCSF (P < 0.025 vs males). CONCLUSIONS:
      Diagnostic accuracy of metabolic evaluation in RCSF increases both with the
      number of urines collected and the time passing after a stone event. Urines
      collected at weekends differ from those of the week only by their lower volumes.
      Abnormalities of RF for calcium nephrolithiasis can be detected in 85.3% of RCSF,
      and HC is the most common RF both in male and female RCSF.

PMID- 9249771
TI  - Ultrasensitive analysis of the intestinal absorption and compartmentalization of
      aluminium in uraemic rats: a 26Al tracer study employing accelerator mass
      spectrometry.
AB  - BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the
      determination of femtogram amounts of 26Al in blood and in various tissues with
      good precision and free of external contamination. METHODS: In the present study
      we used trace quantities of 26Al to investigate the intestinal absorption and
      compartmentalization of aluminium in rats with renal failure (Nx, 5/6
      nephrectomy) and in pair-fed controls (C). Single oral doses of 20 ng 26Al were
      administered to six animals in each group and, subsequently, 24-h post-load 26Al
      was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS:
      Serum concentrations of 26Al were significantly lower in uraemic rats compared to
      controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs
      C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum
      26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake,
      liver and spleen, tended to show a larger degree of aluminium accumulation in
      controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs
      Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of
      extracellular aluminium deposition, 26Al concentrations were more elevated in
      uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al
      accumulation in all measured target tissues was significantly higher in uraemic
      rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from
      tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in
      uraemic animals, suggesting a fractional absorption of 0.133% and 0.175%
      respectively. CONCLUSIONS: Our data suggest that fractional absorption from a
      dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in
      transferrin-dependent target tissues such as liver and spleen; however, in
      quantitative terms extracellular deposition in bone is more important. Uraemia
      has a significant effect on the intestinal absorption and compartmentalization of
      aluminium. It enhances fractional absorption and increases subsequent
      extracellular deposition of aluminium in bone. However, at the same time uraemia
      does not increase transferrin-dependent cellular accumulation of aluminium in
      liver and spleen.

PMID- 9249772
TI  - The pulsatility index and the resistive index in renal arteries. Associations
      with long-term progression in chronic renal failure.
AB  - BACKGROUND: The pulsatility index (PI) and the resistive index (RI) are used as
      pulsed-wave Doppler measurements of downstream renal artery resistance. PI and RI
      have been found to correlate with renal vascular resistance, filtration fraction
      and effective renal plasma flow in chronic renal failure. The aim of the present
      study was to evaluate the potential relationship between these indices and the
      rate of decline in renal function, as reflected by changes in different
      parameters of renal function in patients with chronic renal failure. METHODS:
      Twenty-one patients (8 females; 13 males, mean age 58 years (36-75)) with chronic
      renal failure were enrolled in the study. Doppler examinations were performed in
      the segmental arteries by an Acuson 128XP. The PI and the RI was calculated from
      the blood flow velocities. Parameters of renal function were measured every 3 1/2
      months, and all patients were followed for 18-21 months. Progression of renal
      dysfunction was estimated by linear regression of parameters of renal function
      versus time. RESULTS: In a multiple regression analysis both PI and RI correlated
      significantly to the rate of decline in reciprocal serum creatinine (PI: r = 
      0.48, P = 0.03; RI: r = -0.52, P = 0.02). Furthermore, when separating the
      patients in two groups by the median RI value, there was a significant difference
      between the groups in rate of decline in reciprocal serum creatinine (P = 0.02).
      For PI this distinction was also present (P = 0.04). CONCLUSION: PI and RI
      correlated to the severity of the renal disease, as reflected by the rate of
      decline in reciprocal serum creatinine during antihypertensive treatment. The
      median RI or PI value could separate the patients into groups one of slow and
      another of fast progression.

PMID- 9249773
TI  - Gene expression of LDL receptor, HMG-CoA reductase, and cholesterol-7 alpha
      hydroxylase in chronic renal failure.
AB  - BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic lipid
      profile and an increased risk of ischaemic cardiovascular disease. The associated
      hyperlipidaemia is reportedly ameliorated by erythropoietin (Epo) therapy.
      According to a recent report, rats studied 3 weeks after 5/6 nephrectomy and fed
      a high-protein diet exhibited increased activities of hepatic HMG-CoA reductase
      (HMG-CoAR) and cholesterol 7 alpha-hydroxylase (Ch-7 alpha-H), despite normal
      corresponding mRNA values. DESIGN AND METHODS: This study was designed to examine
      the effects of naturally progressing CRF of longer duration as well as those of
      Epo therapy on gene expressions of the key factors involved in hepatic
      cholesterol metabolism, i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H.
      Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy), Epo
      treated CRF group (given Epo 150 U/kg/twice weekly) and sham-operated, placebo
      treated normal controls. They were allowed free access to regular rat chow and
      studied 6 weeks after surgery. Liver mRNAs and protein mass or activities of the
      above factors were studied. RESULTS: Plasma cholesterol concentration was
      significantly increased in the CRF group (P < 0.001) and was modestly lowered (P
      < 0.05) by Epo therapy. However, microsomal cholesterol concentration and LDLR,
      HMG-CoAR, and Ch-7 alpha-H mRNA as well as HMG-CoAR activity, and Ch-7 alpha-H
      and LDLR protein mass measurements were virtually identical in the three groups.
      Thus, hepatic LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA and protein measurements in
      rats with CRF were similar to those of the normal control group representing an
      inappropriate response to the associated hypercholesterolemia. Epo therapy led to
      partial amelioration of CRF-associated hypercholesterolaemia with no discernible
      effect on hepatic tissue expression of the above factors.

PMID- 9249774
TI  - Low polymorphonuclear cell degranulation during citrate anticoagulation: a
      comparison between citrate and heparin dialysis.
AB  - INTRODUCTION: Haemodialysis (HD)-induced bio-incompatibility includes alterations
      in both cellular elements and humoral factors. As far as polymorphonuclear (PMN)
      cells are concerned, an increase in both adhesion and degranulation has been
      reported. However, whereas increased PMN adherence and aggregation is highly
      linked with early transient complement activation, degranulation seems a
      continuous process, independent from the formation of complement degradation
      products. In the process of cell activation, including PMN degranulation,
      divalent cations (Ca2+) appear to play a pivotal role. As regionally
      administering citrate creates an almost Ca(2+)-free environment within the
      dialyser, it is tempting to speculate that Ca2+ dependent phenomena of bio
      incompatibility, originating within the dialyser, can be attenuated by
      substituting conventional heparin for citrate. METHODS: Therefore, both
      anticoagulation modalities were compared in 10 stable patients, undergoing
      haemodialysis (HD) treatment with cellulose-triacetate membranes (CTA) only.
      Apart from the intracellular granule products myeloperoxidase (MPO) and
      lactoferrin (LF), the classical parameters of bio-incompatibility, peripheral
      blood neutropenia and complement activation, were measured. RESULTS: Analysis of
      MPO and LF gradients across the dialyser (concentration in efferent line
      concentration in afferent line) suggested that degranulation is an early process,
      that occurs mainly within the extracorporeal circuit. Citrate abolished the
      release of MPO almost completely, whereas LF release was partially inhibited.
      Neither neutropenia, nor complement activation could be correlated with the
      occurrence of degranulation. CONCLUSIONS: HD-induced PMN degranulation seems
      largely independent from complement activation, but primarily reliant on Ca2+, at
      least in the case of CTA membranes.

PMID- 9249775
TI  - Influence of hepatitis C virus (HCV) viraemia upon serum aminotransferase
      activity in chronic dialysis patients.
AB  - BACKGROUND: There are many reports concerning HCV in dialysis patients and most
      of them conclude that the clinical and biochemical features of hepatitis C are
      often silent in chronic dialysis patients. Elevated levels of serum alanine
      aminotransferase activity are a sensitive measure of hepatocellular injury, but
      so far the relationship between anti-HCV and ALT among chronic dialysis patients
      has been considered imperfect. To our knowledge, however, such an issue has not
      been adequately addressed. METHODS: Demographic, biochemical, and virological
      data from 506 patients undergoing chronic dialysis treatment in four dialysis
      units in Lombardy, northern Italy were collected in order to assess the influence
      of virological and host factors on serum aminotransferase values. RESULTS:
      Analysis of covariance showed that positivity for anti-HCV antibody was
      significantly associated with raised serum AST (P = 0.0001) and ALT (P = 0.0001)
      levels in the dialysis patients of the whole study group. Logistic regression
      analysis performed in the subset of patients tested for HCV viraemia and genotype
      showed that detectable HCV RNA in serum is a strong predictor of raised AST (P =
      0.0001) and ALT (P = 0.000001) values. Gender showed an independent weak
      influence on AST levels (P = 0.055), serum levels of ferritin were significantly
      (P = 0.042) associated with AST values, the coexistence of HBsAg infection and
      positivity for anti-HCV antibody was independently associated with raised ALT
      levels (P = 0.016). The other factors (including positivity for anti-HCV) showed
      no independent effect on serum aminotransferase levels when they were matched
      with HCV viraemia in our multivariate analysis. HCV RNA positive patients showed
      serum AST (P < 0.008) and ALT levels (P < 0.0001) higher than HCV RNA negative
      patients. There was no relationship between HCV genotypes and liver enzymes.
      CONCLUSIONS: Our data show that detectable HCV RNA in serum is a strong
      independent predictor of raised aminotransferase values in chronic dialysis
      patients; the relationship between serum aminotransferase values and anti-HCV
      antibody was exclusively related to the association between raised
      aminotransferase values and HCV viraemia; HCV RNA positive patients show higher
      hepatic enzyme levels than dialysis patients with no detectable HCV RNA; no
      association between HCV genotype and serum aminotransferase activity was
      apparent.

PMID- 9249776
TI  - Antioxidant status of elderly chronic renal patients treated by continuous
      ambulatory peritoneal dialysis.
AB  - BACKGROUND: An oxidative stress has been reported in patients with chronic renal
      failure (CRF) treated by haemodialysis. To our knowledge, only scant information
      is available concerning CRF patients treated by continuous ambulatory peritoneal
      dialysis (CAPD) with regard to their redox and nutritional status. METHODS: The
      oxidative stress and the biological nutritional status were evaluated in 20
      elderly CRF patients treated by CAPD, compared with a control group of 30 elderly
      non-CRF patients. Plasma peroxidation products were assayed as thiobarbituric
      acid-reactive substances (TBARS), and two enzymatic antioxidant systems were
      determined: erythrocyte superoxide dismutase (SOD), glutathione peroxidase
      activity in plasma (P-GSH-Px) and in erythrocytes (E-GSH-Px). Selenium, vitamin
      E, beta-carotene and vitamin A were evaluated as plasma non-enzymatic
      antioxidants. Nutritional status and iron status were assessed by determining
      serum albumin, prealbumin, iron, ferritin and transferrin concentrations.
      RESULTS: Plasma TBARS concentration was high in both groups (CAPD: 1.37 +/- 0.06
      mumol/l versus non-CRF: 1.41 +/- 0.06 mumol/l; P = NS), compared with usual
      values (0.60 to 1.20 mumol/l), on account of the patients' ages. SOD and E-GSH-Px
      activities were normal in both groups. A significant lowering in P-GSH-Px
      activity was observed only in CAPD patients (211 +/- 14 U/l, usual values: 480 to
      650 U/l). Plasma selenium concentration, decreased in both groups, was
      significantly lower in CAPD than in non-CRF patients (P < 0.01). Plasma vitamin
      E, beta-carotene and vitamin A concentrations were significantly enhanced only in
      CAPD patients (P < 0.0001, P < 0.005 and P < 0.0001, respectively. Biological
      nutritional markers were similar in both groups and within usual values.
      CONCLUSIONS: This study demonstrated the existence of an oxidative stress in CAPD
      treated elderly CRF patients, evidenced by a decrease in plasma selenium levels
      and in P-GSH-Px activity. However, plasma TBARS were not higher in CAPD patients
      than in age-matched non-CRF control subjects, probably on account on the
      patients' ages.

PMID- 9249777
TI  - Assessment of nutritional status in CAPD patients: serum albumin is not a useful
      measure.
AB  - INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of
      nutritional status, although it is recognized that hypoalbuminaemia may be caused
      by many factors. We have further examined the relationship between serum albumin
      and nutrition. METHODS: Nutritional status was assessed by biochemistry,
      anthropometry, mid-arm muscle circumference, muscle strength (hand grip and
      back), and lean body mass (from anthropometry, creatinine kinetics and
      bioimpedance) in a group of 76 stable CAPD patients. Correlations between
      biochemical and nutritional parameters were sought and data were compared between
      patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2
      months apart) and separately according to subjective global assessment score
      (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition).
      RESULTS: In patients with a low SGA score, actual body weight, body mass index,
      mid-arm muscle circumference, lean body mass, subscapular skinfold thickness,
      hand grip strength (males and females) and iliac and triceps skinfold thicknesses
      and back strength (females only) were all significantly less than in patients
      with a normal SGA score. In contrast, none of these variables differed in either
      gender when patients were compared according to serum albumin. Serum albumin was
      correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein
      excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = 
      0.39) in females, but not with any index of body composition in either gender.
      CONCLUSION: Whilst SGA identified a patient group with significantly abnormal
      body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin
      is not a useful marker of malnutrition in stable patients on CAPD.

PMID- 9249778
TI  - Interferon treatment for hepatitis C virus infection in patients on
      haemodialysis.
AB  - BACKGROUND: This study examined the efficacy and tolerability of interferon alpha
      2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in
      patients on maintenance haemodialysis. METHODS: A 24-month prospective cohort
      study was performed in 11 HCV RNA-positive haemodialysis patients, who were
      treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and
      virological monitors included serum alanine aminotransferase levels, and HCV RNA
      by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were
      determined by PCR and nucleotide sequencing. Ten patients had baseline liver
      biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients
      respectively. Six (55%) patients had biochemical and/or histological features of
      chronic active hepatitis before treatment. All 11 patients became HCV RNA
      negative by PCR, with normalization of deranged aminotransferase levels, within 2
      8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks
      after the cessation of IFN, while biochemical relapse occurred in six (55%)
      patients. Sustained eradication of HCV was achieved in three (27%) patients.
      Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x
      10(5) Eq/ml as determined by the bDNA assay, and less severe histological
      abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P
      < 0.05). HCV RNA levels were similar before and after IFN treatment in non
      responders and relapsers. Persistent malaise and poor appetite were noted in
      eight (73%) patients during IFN therapy. Other side-effects of IFN included the
      exacerbation of anaemia, induction of resistance to erythropoietin, weight loss,
      and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV
      infection with IFN can be achieved in 27% of haemodialysis patients. Predictors
      of sustained response include low baseline HCV RNA level and mild liver
      pathology. Virological relapse can occur despite normal liver biochemistry.
      Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute
      the side-effects of IFN that deserve special attention in uraemic subjects.

PMID- 9249779
TI  - Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal
      dialysis patients.
AB  - High serum fluoride (F-) in patients with chronic renal failure (CRF) and end
      stage renal disease (ESRD) is associated with risk of renal osteodystrophy and
      other bone changes. This study was done to determine F- in normal healthy
      controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis
      (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on
      dialysis (17 males, 22 females) were recruited in the study in a community with
      47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water.
      Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l.
      Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range
      0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean
      serum F- concentration did not correlate significantly with age and sex among
      control subjects, whereas such correlation was observed in patients with ESRD on
      dialysis. Mean serum F- concentration was significantly higher in patients on
      dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When
      grouped according to sex, the mean serum F- concentration in males (3.05 +/-
      1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/-
      1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it
      was observed that F- concentration was significantly higher in patients with age
      groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/-
      0.531). Thus F- concentration correlated with age and sex, being higher in males
      and above 20 years. Despite appreciable clearance of F- (39-90%) across the
      peritoneum, patients on CAPD showed higher serum F- concentration than those on
      HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis
      39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal
      osteodystrophy.

PMID- 9249780
TI  - Recurrence of haemolytic-uraemic syndrome in renal transplants: a single-centre
      report.
AB  - BACKGROUND: The incidence of recurrence of haemolytic-uraemic syndrome (HUS) in
      renal allografts appears to vary by centre, with the highest rates reported from
      the University of Minnesota. It is possible that the high rate of HUS recurrence
      at this institution reflects a transplant population skewed towards patients with
      a form of HUS that is more likely to recur in the allograft. METHODS: This study
      examined whether the initial episode of HUS in the native kidneys was preceded by
      a diarrhoeal prodrome ('classical HUS') or not ('atypical HUS'), and evaluated
      transplant outcomes in 24 patients who received 36 transplants at the University
      of Minnesota between 31 May 1972 and 31 December 1994. RESULTS: Eighteen of the
      24 patients had atypical HUS, three had classical HUS, and in three patients the
      presence or absence of a diarrhoeal prodrome could not be determined. Recurrent
      HUS, defined as microangiopathic haemolytic anaemia, thrombocytopenia, renal
      insufficiency, and allograft biopsy findings compatible with HUS, occurred 16
      times in 14 grafts in 11 patients. Nine of these patients had atypical HUS, one
      had classical HUS, and in one the nature of the prodrome could not be determined.
      Eleven of the 14 initial recurrences took place within 2 months of transplant.
      Recurrence was not more frequent in patients who received cyclosporin or
      antilymphocyte preparations. Actuarial analysis using matched controls showed
      poorer graft survival in patients with a primary diagnosis of HUS (P = 0.007),
      due to the high frequency of graft loss in HUS patients with recurrence.
      CONCLUSION: Based upon these data and a review of the literature, it can be
      concluded that the risk of recurrence of HUS in the allograft is confined almost
      entirely to patients with atypical forms of HUS.

PMID- 9249781
TI  - Autosomal dominant polycystic kidney disease in a kidney transplant population.
AB  - AIM: To define specific manifestations of autosomal dominant polycystic kidney
      disease in kidney transplant patients. METHODS: Of 874 consecutive first renal
      transplant patients 1985-1993, 114 (13%) had autosomal dominant polycystic kidney
      disease (ADPKD). Mean age was 53 +/- 8 years, 62% were men, and 83% received
      cadaveric kidneys. Control patients were matched for sex, age and donor type.
      Median follow-up time was 63 months. One patient was lost to follow-up. Medical
      records before and after transplantation were reviewed. RESULTS: Survival of
      patients and grafts was similar in ADPKD patients and controls. Twenty-five ADPKD
      patients died, four of causes not seen in the controls; two aortic aneurysms, one
      urothelial cancer, one colon perforation. Four more ADPKD patients but no control
      had diverticulitis (P = 0.03), two with perforation. Cardiovascular morbidity was
      not increased. Eight patients had subarachnoidal haemorrhage before
      transplantation and two during follow-up. Nineteen patients had undergone
      nephrectomy before transplantation, 11 because of voluminous kidneys, five for
      infection, pain or bleeding, two for suspected malignancy, one for hypertension.
      After transplantation, seven patients underwent nephrectomy, only one related to
      kidney size. During the first year, need of phlebotomy occurred in 14% of
      patients versus 4% of controls, P = 0.02. Urinary tract infection rates were not
      increased. No morbidity was related to liver cysts. CONCLUSION: The specific
      features of kidney transplantation to patients with ADPKD were few: enlarged
      kidneys, relevant only before transplantation, erythrocytosis, and as rare but
      serious events, diverticulitis with perforation.

PMID- 9249782
TI  - L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant
      patients.
AB  - BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and
      to have an antinatriuretic effect. The existence of an interference of
      cyclosporin with the vasodilating properties of endothelium mediated by nitric
      oxide production could mediate these effects. On the other hand, the infusion of
      the nitric oxide precursor L-arginine has been shown to induce renal
      vasodilatation and to facilitate natriuresis in normal volunteers. We have
      investigated the renal effects of the administration of an infusion of L-arginine
      in renal transplant patients chronically treated with cyclosporin. To facilitate
      the analysis of the data the effects of the administration of a similar dose of
      cyclosporin on renal function during the infusion of a vehicle were also
      investigated during the administration of a vehicle of L-arginine. DESIGN: Ten
      male renal transplant patients, chronically treated with cyclosporin and with a
      stable renal function were studied during 2 consecutive days after the
      administration of the usual morning dose of cyclosporin. The first day they
      received an intravenous infusion of vehicle and the second the infusion of graded
      doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The
      first day, after cyclosporin administration a significant fall (P < 0.01) was
      observed in natriuresis and kaliuresis in the absence of changes in renal plasma
      flow and glomerular filtration rate. After the administration of L-arginine
      significant (P < 0.01) increases of renal plasma flow, glomerular filtration
      rate, and natriuresis were seen. The increase in blood levels of cyclosporin
      after its administration did not differ between days 1 and 2. CONCLUSION: These
      results indicate that L-arginine facilitates renal vasodilatation and natriuresis
      in renal transplant patients. Furthermore, the observed increase in sodium
      excretion could indicate that L-arginine counteracts the antinatriuretic effect
      of cyclosporin.

PMID- 9249783
TI  - Blood pressure independent effects of nitrendipine on cardiac structure in
      patients after renal transplantation.
AB  - Left ventricular hypertrophy is well established as a blood pressure independent
      cardiovascular risk factor in patients on renal replacement therapy. The effects
      of antihypertensive treatment on myocardial structure and function in renal
      transplant recipients have been so far only rarely investigated. In a double
      blind, placebo-controlled study patients were randomized to the calcium channel
      blocker nitrendipine or placebo if the transplanted kidney had developed a stable
      phase. Normotensive patients received nitrendipine 2 x 5 mg daily or placebo,
      hypertensive patients received 2 x 10 mg up to 2 x 20 mg nitrendipine daily or
      placebo. To achieve adequate blood pressure control, all patients with still
      elevated blood pressure on study medication received antihypertensive drugs other
      than calcium channels blockers. Ambulatory blood pressure recording and 2D-guided
      M-mode echocardiography were performed at baseline and upon completion of the
      study. In addition, laboratory workup (including serum creatinine and lipids) was
      done, and serum aldosterone, plasma renin activity, plasma angiotensin II and
      blood glucose levels were measured in all patients at baseline and after at least
      12 months of therapy. Ambulatory blood pressure was almost identical between both
      groups at study baseline and follow-up. In renal transplant patients on
      nitrendipine, posterior wall thickness (-0.10 +/- 1.77 mm) and septal wall
      thickness (-0.83 +/- 2.23 mm) did not change significantly from baseline. In
      contrast, posterior wall thickness (0.71 +/- 0.92 mm, P < 0.01) and septal wall
      thickness (0.97 +/- 2.20 mm, P < 0.05) increased in patients on placebo, which
      differed from the observed changes on nitrendipine (ANOVA: P = 0.093 and P =
      0.048, respectively). Relative wall thickness, a parameter for concentric left
      ventricular hypertrophy, became numerically smaller on nitrendipine therapy from
      0.46 +/- 0.07 to 0.44 +/- 0.09 (-0.02 +/- 0.09, NS) but increased from 0.42 +/-
      0.08 to 0.48 +/- 0.08 in the placebo arm (+0.04 +/- 0.08, P < 0.02), which was
      also significant between the two groups (ANOVA: P = 0.036). Endocrine parameters,
      lipids and blood glucose were not different between the two groups. We conclude
      from these data that the calcium channel blocker nitrendipine exerted beneficial
      effects on cardiac structure in patients after renal transplantation independent
      of blood pressure.

PMID- 9249784
TI  - Arterial injuries following diagnostic, therapeutic, and accidental arterial
      cannulation in haemodialysis patients.
AB  - BACKGROUND: Incidence of iatrogenic arterial lesions is currently increasing and
      patients undergoing dialysis represent a group at high risk since they require
      repeated cannulation of the vascular access and intermittent heparinization
      during maintenance haemodialysis. CLINICAL REPORTS: Between 1992 and 1995 we
      treated four vascular lesions (two pseudoaneurysms and two arteriovenous
      fistulae) with surgery in three patients undergoing dialysis at our centre. No
      postoperative morbidity and mortality was observed; in all cases surgery was
      effective. CONCLUSIONS: Although conservative treatment (US guided compression)
      of arterial lesions shows promising results, in patients undergoing dialysis
      combined with heparinization it seems less suitable. In these patients, early
      detection of post-cannulation pseudoaneurysms or arteriovenous fistulae allows
      surgical treatment, with low morbidity rate and satisfactory long-term outcome.

PMID- 9249785
TI  - Purification and localization of a 25-kD porcine renal puromycin aminonucleoside
      binding protein.
AB  - BACKGROUND: Reactive oxygen species (ROS) are considered to have a role in the
      progression of puromycin aminonucleoside (PAN) nephrosis. However, the exact
      mechanism by which PAN induces ROS in this model is little known. In the present
      study, we attempted to purify a candidate for the target protein from PAN
      nephrotoxicity. METHODS: Using PAN-affinity column chromatography, a series of
      PAN-binding proteins was isolated from porcine renal extracts. We produced a
      specific antibody against a 25-kD protein eluted from the PAN-affinity matrix,
      and then developed a method to purify this protein. A partial amino acid sequence
      of the 25-kD PAN-binding protein was determined, and its tissue distribution was
      examined by immunoblot and immunohistochemical studies. RESULTS: The purified 25
      kD PAN-binding protein was identified as a renal homolog of a new member of
      NAD(P)H:quinone oxidoreductases (NQOs, EC 1.6.99.2) that suppress the semiquinone
      and superoxide anion formation in cells, designated NQO2. Immunoblot analysis
      revealed a higher expression of the 25-kD PAN-binding protein in the kidney,
      brain, and liver among porcine major organs. Immunohistochemical studies showed
      an intrarenal distribution of this protein in epithelial cells of the glomeruli
      and tubules, mesangial cells, and vascular smooth muscle cells. CONCLUSIONS: We
      have purified the renal homolog of NQO2 as a PAN-binding protein, and shown its
      unique tissue expression. PAN may bind to the NQO2 homolog and inhibit its
      function in the renal target cells. This is presumed to result in an increase of
      ROS in the kidney with PAN nephrosis.

PMID- 9249786
TI  - Ethylene oxide allergy in dialysis patients.
AB  - DESIGN OF STUDY: Two groups of patients undergoing long-term dialysis were
      studied in order to evaluate the importance of ethylene oxide (EtO) in causing
      allergic reactions during dialysis. The first group of 50 subjects had never
      shown any hypersensitivity reactions related to dialysis, whereas the second
      group of 20 subjects had previously complained of reactions. All the patients
      underwent a prick test with a standard kit of aeroallergens in order to assess
      the presence of atopy (in doubtful cases a RAST test was carried out with the
      same aeroallergens). A blood sample for the investigation of EtO specific IgE
      antibodies was taken from all the patients; the immunoenzymatic method was used.
      RESULTS: Sensitivity to EtO is significantly higher in the group of patients with
      previous allergic reactions during dialysis (55 vs 6% in the control group).

PMID- 9249787
TI  - Validation in the sheep of an ultrasound velocity dilution technique for
      haemodialysis graft flow.
AB  - BACKGROUND: A simple, rapid, inexpensive method for measuring the flow in a
      patient's vascular access would permit routine monitoring during haemodialysis,
      and hence provide information of access graft deterioration sufficiently early to
      increase the success of minimally invasive remedial procedures. This paper
      reports the validation of such a method in animals. METHODS: A PTFE graft was
      implanted in sheep between the carotid artery and the jugular vein. While the
      sheep was under general anaesthesia and on an haemodialysis circuit, ultrasound
      velocity in its blood was perturbed by the injection of a 5-10 ml bolus of
      isotonic NaCl. The pump tubing flow was measured by a transit-time blood flow
      meter. This flow was combined with the areas of perturbation generated by the
      injection before and after mixing in the access flow to estimate graft flow. The
      calculated graft flow was compared to flow measured directly by a transit-time
      probe on the same carotid artery. RESULTS: Over a 10-fold range, 120-1260 ml/min,
      graft flow measured by ultrasound velocity dilution agreed well with graft flow
      measured directly with a scatter of 76 ml/min about the regression line.
      CONCLUSION: Ultrasound velocity dilution provides a method for measuring flow in
      the graft accurate enough for clinical evaluation of patients on dialysis.

PMID- 9249788
TI  - Familial interstitial nephritis and retinitis pigmentosa.

PMID- 9249789
TI  - Thrombotic thrombocytopenic purpura and acute renal failure in adult Still's
      disease.

PMID- 9249790
TI  - Normocalcaemic hepatorenal sarcoidosis with crescentic glomerulonephritis.

PMID- 9249791
TI  - Coincidence of myasthenia gravis and antiglomerular basement membrane
      glomerulonephritis: a combination of two antibody-mediated autoimmune diseases on
      day 15.

PMID- 9249792
TI  - Caroli's disease and autosomal dominant polycystic kidney disease: a rare
      association?

PMID- 9249793
TI  - Type IV renal tubular acidosis and uric acid nephrolithiasis in William's
      syndrome--an unusual mode of renal involvement.

PMID- 9249794
TI  - Spiral CT angiography for discriminating between megacalyces and intermittent
      hydronephrosis.

PMID- 9249795
TI  - Bilateral primary renal Burkitt lymphoma in a child presenting with acute renal
      failure.

PMID- 9249796
TI  - Acute renal failure induced by nimesulide in a patient suffering from temporal
      arteritis.

PMID- 9249797
TI  - Acute renal failure associated with immunoglobulin administration.

PMID- 9249798
TI  - Renal failure in a patient with chronic myelomonocytic leukaemia.

PMID- 9249799
TI  - Fabry's disease presenting with oligoanuric end-stage renal failure.

PMID- 9249800
TI  - Pyoderma gangrenosum and spinal epidural abscess after subcutaneous
      administration of recombinant human erythropoietin.

PMID- 9249801
TI  - Xanthogranulomatous pyelonephritis caused by Surgical in a renal allograft.

PMID- 9249802
TI  - Popliteal cysts from advanced amyloidosis in long-term
      haemofiltration/haemodiafiltration.

PMID- 9249803
TI  - The female patient with faints and fatigue: don't forget Sjogren's syndrome.

PMID- 9249804
TI  - The fundus in malignant hypertension.

PMID- 9249805
TI  - Glomerulonephritis and non-Hodgkin lymphoma.

PMID- 9249806
TI  - Arthur Arnold Osman (1893-1972): a forgotten pioneer of nephrology.

PMID- 9249807
TI  - Keep your eyes skinned. Varicella Zoster.

PMID- 9249809
TI  - Exacerbation of microscopic polyarteritis with azathioprine.

PMID- 9249808
TI  - VEGF and diabetic microvascular complications.

PMID- 9249810
TI  - Proteinuria in healthy individuals over 75 years of age.

PMID- 9249811
TI  - Goodpasture's syndrome with normal renal function.

PMID- 9249812
TI  - Simultaneous relapse of minimal-change glomerulonephritis and Graves' disease.

PMID- 9249813
TI  - Colchicine agranulocytosis.

PMID- 9249814
TI  - A rare cause of acute tubulointerstitial nephritis: Salmonella typhimurium
      infection.

PMID- 9249815
TI  - Another case of acute renal failure (ARF) due to acute tubular necrosis (ATN),
      proven by renal biopsy in non-fulminant hepatitis A virus (HAV) infection.

PMID- 9249816
TI  - Peritonitis by Aureobasidium pullulans in continuous ambulatory peritoneal
      dialysis.

PMID- 9249817
TI  - Pitfalls in diagnostic cervicovaginal cytology.

PMID- 9249818
TI  - Errors in cervical smears: minimizing the risk of medicolegal consequences.
AB  - Cytologists need to critically evaluate their practices and practice settings to
      ensure that what they do and how they document what they do will withstand both
      regulatory and legal scrutiny. Any individual involved in cytology as a
      laboratory owner, operator, director, supervisor, technical or staff employee,
      independent agent, or customer representative is a potential target of cytology
      malpractice litigation. All of these individuals must participate in the risk
      management process. For the laboratory as a corporate entity, business and
      technical practices, including quality control and quality assurance procedures,
      must be contemporary, legitimate, and justifiable. Sound scientific evidence and
      well-subscribed standards of practice supporting an individual's or laboratory's
      conduct are the best defenses to malpractice claims. For the near future,
      litigation will continue to focus on false-negative Pap smears on a case-by-case
      basis. Laboratories and individuals can reduce the risk of malpractice liability
      by directing their attention to proactive quality control and quality assurance
      methods. But in the final analysis, consumer education about the benefits and
      limitations of the Pap test is key to limiting malpractice claims.

PMID- 9249819
TI  - Errors and pitfalls in lung and pleural cytology.

PMID- 9249820
TI  - Errors and pitfalls in cytology of the lower urinary tract.

PMID- 9249821
TI  - Problems and pitfalls in thyroid cytology.
AB  - When performing fine-needle aspiration of the thyroid, the limitations of the
      technique must be considered and one must keep an open mind when examining the
      cytologic specimen. It is also important to develop a philosophy for handling the
      occasional difficult "gray zone" case. Some cases will be at the border of normal
      and abnormal and a philosophical approach concerning how to handle these problem
      cases is useful. One approach is to "play it safe" and classify as "suspicious"
      any lesion that clearly does not fit into a benign category. Sometimes, a
      discussion with clinicians about the degree of suspicion is appropriate, and
      minimally suspicious lesions might be followed up unless clinical indications
      point toward surgery. An intermediate to strong degree of cytologic suspicion
      usually mandates surgical exploration. Undoubtedly, we will continue to refine
      our diagnostic abilities in fine-needle aspiration cytology of the thyroid. The
      above discussion reflects the experience of one institution, represents the state
      of the art as of 1996 and may have to be revised in the near future.

PMID- 9249822
TI  - Errors and pitfalls in diagnostic cytology: new techniques applied to
      cytopathology.

PMID- 9249823
TI  - Pitfalls in the diagnosis of fine-needle aspiration of lymph nodes.

PMID- 9249824
TI  - Pitfalls in cytology of the breast.

PMID- 9249825
TI  - Errors and pitfalls in diagnostic cytology of abdominal organs.

PMID- 9249826
TI  - Nomenclature and characterization of transisthmus conduction after ablation of
      typical atrial flutter.

PMID- 9249827
TI  - Preimplant atrial defibrillation testing with a temporary catheter in sheep.
AB  - Prior to implantation of an atrial defibrillator, its effectiveness should be
      tested in each patient. A new catheter design for temporary use with electrodes
      for atrial defibrillation, electrogram sensing, and pacing was tested in this
      study. Atrial defibrillation thresholds defined using this temporary catheter
      were compared to the ones defined by catheters intended for chronic use with an
      implantable atrial defibrillator. Atrial defibrillation threshold was determined
      in six sheep using both types of catheters. Each animal was subjected to studies
      on 2 consecutive days. On the first day, shocks were applied between two of the
      temporary catheters. On the following day, permanent leads were inserted and
      atrial defibrillation threshold was redetermined. In both cases, defibrillation
      electrodes were positioned in the same heart location with one electrode in the
      distal coronary sinus and the second electrode in the right atrium. Atrial
      defibrillation threshold was obtained using 10 V increments or decrements to
      determine the lowest shock intensity needed to defibrillate the atria. Threshold
      was defined as the shock intensity at which 20 shock percent success was at or
      between 15% and 85%. Statistical analysis showed no significant difference (P <
      0.05) between atrial defibrillation threshold energy (0.53 J vs 0.55 J), voltage
      (122 V vs 120 V) or current (2.2 A vs 2.6 A) measured with the temporary
      catheters and the permanent leads, respectively. These data indicate that
      temporary catheters can be used for efficacy testing prior to implant of an
      atrial defibrillator, and that they predict atrial defibrillation threshold
      adequately for chronic leads.

PMID- 9249828
TI  - The medical therapy of cardioinhibitory syncope in pediatric patients.
AB  - A small percentage of pediatric patients with neurally mediated syncope will have
      an asystolic response during upright tilt table testing. The purpose of this
      study is to evaluate the incidence of asystole during tilt table testing, and to
      assess the outcome of medical management of such patients. Of 398 patients
      undergoing evaluation for recurrent syncope between January 1989 and 1994, 18
      (4.5%) experienced asystole lasting > or = 5 seconds during baseline tilt test.
      Patients had experienced a mean of four episodes of syncope, with a mean age at
      the time of tilt test of 11.1 +/- 4.0 years. The median duration of asystole was
      10 seconds (range 5-40 s). Treatment was individualized to increased fluids and
      salt intake (3 patients), metoprolol (8 patients), pseudoephedrine (4 patients),
      disopyramide (1 patient), or combination therapy with fludrohydrocortisone (2
      patients). During a median duration of follow-up of 31 months, no additional
      syncope was experienced by 78% of patients. Recurrent syncope in 4 patients was
      associated with either noncompliance or discontinuation of therapy in 3 patients;
      in 1 patient, increasing the dose of metoprolol was effective in preventing
      recurrences. We conclude that young patients with recurrent syncope and asystole
      during tilt test may be safely and effectively managed with pharmacological
      therapy, without resorting to pacemaker implantation.

PMID- 9249829
TI  - AAIR versus DDDR pacing in patients with impaired sinus node chronotropy: an
      echocardiographic and cardiopulmonary study.
AB  - The aim of this study was to compare AAIR and DDDR pacing at rest and during
      exercise. We studied 15 patients (10 men, age 65 +/- 6 years) who had been paced
      for at least 3 months with activity sensor rate modulated dual chamber
      pacemakers. All had sick sinus syndrome (SSS) with impaired sinus node
      chronotropy. The patients underwent a resting echocardiographic evaluation of
      systolic and diastolic LV function at 60 beats/min during AAIR and DDDR pacing
      with an AV delay, which ensured complete ventricular activation capture. Cardiac
      output (CO) was also measured during pacing at 100 beats/min in both pacing
      modes. Subsequently, the oxygen consumption (VO2AT) and VO2AT pulse at the
      anaerobic threshold were measured during exercise in AAIR mode and in DDDR mode
      with an AV delay of 120 ms. The indices of diastolic function showed no
      significant differences between the two pacing modes, except for patients with a
      stimulus-R interval > 220 ms, for whom the time velocity integral of LV filling
      and LV inflow time were significantly lower under AAI than under DDD pacing. At
      60 beats/min, CO was higher under AAI than under DDD mode only when the stimulus
      R interval was below 220 ms. For stimulus-R intervals longer than 220 ms, and
      also during pacing at 100 beats/min, the CO was higher in DDD mode. The stimulus
      R interval decreased in all patients during exercise. The time to anaerobic
      threshold, VO2AT, and VO2AT pulse showed no significant differences between the
      two pacing modes. Our results indicate that, at rest, although AAIR pacing does
      not improve diastolic function in patients with SSS, it maintains a higher CO
      than does DDDR pacing in cases where the stimulus-R interval is not excessively
      prolonged. On exertion, the two pacing modes appear to be equally effective, at
      least in cases where the stimulus-R interval decreases in AAIR mode.

PMID- 9249830
TI  - Comparison of sensitivity and specificity of tilt protocols with and without
      isoproterenol in children with unexplained syncope.
AB  - Head-up tilt testing with or without isoproterenol is extensively used in the
      evaluation of patients with unexplained syncope. However, sensitivity and
      specificity of tilt protocols with and without isoproterenol have not been
      clarified in children, due to lack of age matched control subjects. This study
      was designed to assess and to compare the sensitivity and specificity of tilting
      alone and tilting in conjunction with isoproterenol. Thirty children with
      unexplained syncope (group I) and 15 age-matched control subjects (control group
      I) underwent successive 60 degrees head-up tilts for 10 minutes during infusions
      of 0.02, 0.04, and 0.06 microgram/kg/min of isoproterenol, after a baseline tilt
      to 60 degrees for 25 minutes. Also, 35 children (group II) with unexplained
      syncope and 15 healthy control subjects (control group II) were evaluated by head
      up tilt to 60 degrees for 45 minutes without an infusion of isoproterenol. In
      response to tilt protocol with graded isoproterenol, 23 (76.6%) of the patients
      in group I and 2 of the 15 (13.3%) control subjects developed syncope.
      Accordingly, the sensitivity of tilt testing with isoproterenol was 76.6%, and
      its specificity was 86.7%. Tilt testing without isoproterenol was positive in 17
      (48.5%) of the patients in group II but in only 1 of the 15 (6.6%) control
      subjects. Thus, sensitivity and specificity of tilt testing without isoproterenol
      were 48.5% and 93.4%, respectively. The mean heart rate and systolic blood
      pressure decreased significantly (P < 0.001) in all tilt positive patients during
      syncope. In conclusion, the head-up tilt test is a valuable diagnostic test in
      the evaluation of children with unexplained syncope, and isoproterenol is likely
      to increase the sensitivity of the test without decreasing its specificity.

PMID- 9249831
TI  - Vibration, acceleration, gravitation, and movement: activity controlled rate
      adaptive pacing during treadmill exercise testing and daily life activities.
AB  - Activity-based sensors for rate adaptive pacing have been available for several
      years and now include several different types: vibration; acceleration;
      gravitation; and movement. However, a systematic comparison evaluating the
      relative advantages and disadvantages of these various sensors has received
      little study. The purpose of the present study was to compare these sensor
      subtypes using treadmill testing and an outdoor test circuit, which simulated
      daily life activities and included both uphill and downhill walking. Pacemakers
      were strapped on the chest of healthy volunteers and connected to one channel of
      an ambulatory recording device, which also recorded the subject's intrinsic heart
      rate. The pacemakers were programmed using an initial treadmill test to
      standardize the rate responsive parameters for each device. Nine different
      pacemaker models were studied including 3 vibration-based (Elite, Synchrony,
      Metros), 4 acceleration-based (Relay, Excel, Ergos, Trilogy), 1 gravitational
      based (Swing), and 1 movement-based (Sensorithm) device. All devices demonstrated
      a prompt rate response with casual walking on flat ground. The vibration-,
      gravitational-, and movement-based pacemakers showed a pronounced rate decline
      during more strenuous work, e.g., walking uphill. This phenomenon was absent in
      the accelerometer-based units. In particular, the vibration- and movement-based
      units showed a higher rate with walking downhill compared to uphill. An optimally
      tuned rate behavior on the treadmill usually did not provide an optimal rate
      behavior during daily activities and there was a tendency to overstimulation
      during low workload. The development of the two newest sensors (gravitational and
      movement) did not result in an improved performance of rate response behavior.
      Overall, the accelerometer-based pacemakers simulated or paralleled sinus rate
      behavior the most closely.

PMID- 9249832
TI  - Comparison of electrical characteristics between a steroid-eluting single-pass
      VDD lead and a standard steroid-eluting ventricular lead. Thera Pacemaker Study
      Group.
AB  - Compared to regular ventricular leads, single-pass VDD leads have two additional
      floating electrodes proximal to the ventricular tip, which enables them to detect
      atrial signals. Because of the latter, VDD leads are thicker than ventricular
      leads, which could affect ventricular pacing. The purpose of the present study
      was to compare ventricular pacing of a steroid-eluting single-pass VDD lead
      (CapSure VDD, Medtronic; n = 107) with the same steroid-eluting regular lead
      (CapSure SP, Medtronic; n = 39) implanted in the ventricle; both leads were
      connected to the same types of pacemakers. At implantation, pacing thresholds
      were measured at 0.5-ms pulse duration and impedance by means with the PSA. At
      discharge, as well as after 1 and 3 months, pulse duration thresholds were
      determined at 2.5 V pulse amplitude and impedance by telemetry. At implantation,
      pacing thresholds and impedance were not different in the VDD (0.38 +/- 0.16 V;
      691 +/- 122 omega) and ventricular lead group (0.44 +/- 0.17 V; 648 +/- 150
      omega). During follow-ups, no differences in pulse duration threshold were
      detected between the two groups neither at discharge (VDD = 0.05 +/- 0.03 ms;
      ventricular 0.05 +/- 0.02 ms), nor after 1 (VDD = 0.05 +/- 0.02 ms; ventricular
      0.08 +/- 0.07 ms) and 3 months (VDD = 0.06 +/- 0.03 ms; ventricular 0.09 +/- 0.10
      ms). There were also no significant differences for impedance at discharge (VDD =
      675 +/- 113 omega; ventricular = 594 +/- 113 omega), after 1 (VDD = 678 +/- 131
      omega; ventricular = 627 +/- 112 omega) and 3 months (VDD = 652 +/- 99 omega;
      ventricular = 628 +/- 105 omega). Pacing thresholds and impedance were neither
      significantly different at implantation nor during follow-ups between patients
      with steroid-eluting VDD leads and patients with an equivalent ventricular lead
      indicating that the thicker VDD lead does not affect ventricular pacing.

PMID- 9249833
TI  - Predictors of psychosocial adjustment in patients with implantable cardioverter
      defibrillators.
AB  - Predictors of psychological distress/adjustment were examined in 25 patients
      following placement of ICDs. Patients completed a demographic questionnaire and a
      standardized questionnaire of psychological symptoms (i.e., Symptom Checklist-90
      Revised; SCL-90-R). The number of discharges categorized by the patient as
      inappropriate and appropriate were also ascertained. The number of ICD discharges
      categorized as inappropriate and diminished levels of physical activity (r = 0.53
      and 0.63, P < 0.01, respectively) did significantly relate to overall
      psychological distress. In addition, after controlling for age and prior
      psychiatric and physical health status through a stepwise multiple regression
      analysis, the occurrence of ICD discharges categorized as inappropriate and
      diminished physical activity continued to significantly predict overall
      psychological distress (R2 = 0.41, P < 0.01). However, the number of ICD
      discharges categorized as appropriate did not significantly predict overall
      psychological distress. The results of this investigation suggest that further
      refinement of the ICD could reduce the risk of exposure to potential
      psychological distress, and an analysis of prior and anticipated patient physical
      activity levels should be a factor when calibrating minimum ICD discharge
      threshold levels.

PMID- 9249834
TI  - Autonomic effects on noise recorded during signal-averaged electrocardiography.
AB  - The purpose of this study was to assess the effects of autonomic stimulation and
      blockade on noise levels and to compare the noise measurements in the ST and TP
      segments of the signal-averaged ECG. Five-minute electrocardiographic data were
      recorded in 14 normal volunteers (8 males and 6 females; mean age 28.5 +/- 5.0
      years) on two separate days (day 1-baseline, epinephrine infusion, isoproterenol
      infusion, beta-blockade, and combined adrenergic and parasympathetic blockade;
      day 2-baseline, phenylephrine infusion, parasympathetic blockade, and during
      phenylephrine infusion following atropine). Signal averaging was done off-line on
      100 beats and noise was measured in both the ST and TP segments as the standard
      deviation of voltage in the segment of interest. For all conditions tested, the
      mean noise level measured in the ST segment (0.46 +/- 0.16 microV) was
      significantly less than that measured in the TP segment (0.52 +/- 0.24 microV; P
      = 0.0003), but there was good correlation between the noise measured in the ST
      and the TP segment (R2 = 0.62, P < 0.0001). Noise increased with isoproterenol
      infusion and decreased following adrenergic blockade. In addition, day 2 baseline
      noise was less than baseline noise on day 1. Finally, neither parasympathetic
      stimulation or blockade nor alpha-adrenergic stimulation significantly affected
      signal-averaged electrocardiography (SAECG) noise levels. Thus, the data support
      the notion that enhanced sympathetic tone increases noise levels and beta
      adrenergic blockade may decrease noise levels, likely due to effects from muscle
      sympathetic nerve activity. These findings are important since the target
      population for the SAECG are patients with myocardial infarction and congestive
      heart failure, conditions associated with increased sympathetic tone, which may
      in turn impact on the reproducibility or technical aspects of the SAECG. In
      addition, because noise in the ST and TP segments are highly correlated and the
      noise measured in the ST segment is less than that in the TP segment, uniform
      adoption of noise measurement in the ST segment seems most appropriate.

PMID- 9249835
TI  - Initial experience with a co-radial bipolar pacing lead.
AB  - A new type of endocardial bipolar pacing lead has been designed to overcome the
      potential drawbacks of the conventional coaxial bipolar pacing lead. We
      prospectively evaluated the new co-radial bipolar pacing leads (Intermedics Thin
      Line), which are thinner (5 Fr vs 6-8 Fr) than standard coaxial bipolar leads. X
      ray visibility and lead handling were subjectively assessed (excellent, good,
      adequate, or poor) at implant; lead impedance, sensitivity threshold, and pacing
      threshold were measured at implant, then at 1, 3, 6, 12, and 18 months. The
      results were as follows: 103 patients (51 M; age 63.8 +/- 17.4 years) received 71
      atrial (A) and 89 ventricular (V) leads. X-ray visibility was excellent in
      59/103; good in 23/103; adequate in 11/103; and poor in 10/103. Overall handling
      was excellent in 56/71 A and 69/89 V; good in 11/71 A and 18/89 V; adequate in
      3/71 A and 1/89 V; poor in 1/71 A and 1/89 V. There were two perioperative
      complications. At implant: impedance in A and V were 370.1 +/- 74.7 and 501.5 +/-
      124.4 omega, sensing thresholds in A and V were 3.0 +/- 1.5 and 9.9 +/- 5.0 mV,
      pacing thresholds at 0.45 ms in A and V were 0.59 +/- 0.21 and 0.41 +/- 0.15
      volt, respectively. At 1, 3, 6, 12, and 18 months of follow-up: no pacing lead
      related complications were reported; pacing lead characteristics remained
      outstanding and stable. This new lead appears to have significant clinical
      advantages over the conventional coaxial bipolar pacing lead. Long-term follow-up
      is required to confirm its reliability and chronic performance characteristics.

PMID- 9249836
TI  - Evaluation of the safety and efficacy of deep sedation for electrophysiology
      procedures administered in the absence of an anesthetist.
AB  - Several procedures performed in the electrophysiology laboratory (EP lab) require
      surgical manipulation and are lengthy. Patients undergoing such procedures
      usually receive general anesthesia or deep sedation administered by an
      anesthesiologist. In 536 consecutive procedures performed in the EP lab, we
      assessed the safety and efficacy of deep sedation administered under the
      direction of an electrophysiologist and in the absence of an anesthetist.
      Patients were monitored with pulse oximetry, noninvasive blood pressure
      recordings, and continuous ECGs. The level of consciousness and vital signs were
      evaluated at 5-minute intervals. Deep sedation was induced in 260 patients using
      midazolam, phenergan, and meperidine, then maintained with intermittent dosing of
      meperidine at the following mean doses: midazolam 0.031 +/- 0.024 mg/kg;
      phenergan 0.314 +/- 0.179 mg/kg; and meperidine 0.391 +/- 0.167 mg/kg per hour.
      In the remaining 276 patients, deep sedation was induced with midazolam and
      fentanyl and maintained with a continuous infusion of fentanyl at a mean dose of
      2.054 +/- 1.43 micrograms/kg per hour. Fourteen patients experienced a transient
      reduction in oxygen saturation that was readily reversed following administration
      of naloxone. An additional 11 patients desaturated secondary to partial airway
      obstruction, which resolved after repositioning the head and neck. Fourteen
      patients experienced hypotension with fentanyl. All but one returned to baseline
      blood pressures following an infusion of normal saline. No patient required
      intubation and no death occurred. Only three patients had recollection of
      periprocedure events. No patient remembered experiencing pain with the procedure.
      Hospital stays were not prolonged as a result of the sedation used. IN
      CONCLUSION: (1) deep sedation during EP procedures can be administered safely
      under the guidance of the electrophysiologist without an anesthetist present; (2)
      the drugs used should be readily reversible in case of respiratory depression;
      and (3) this approach may reduce the overall cost of the procedures in the EP
      lab, maintaining adequate patient comfort.

PMID- 9249837
TI  - A gastroesophageal electrode for atrial and ventricular pacing.
AB  - Temporary transvenous cardiac pacing requires technical expertise and access to
      fluoroscopy. We have developed a gastroesophageal electrode capable of atrial and
      ventricular pacing. The flexible polythene gastroesophageal electrode is passed
      into the stomach under light sedation. Five ring electrodes, now positioned in
      the lower esophagus, are used for atrial pacing. A point source (cathode) on the
      distal tip of the electrode, now positioned in the gastric fundus, is used for
      ventricular pacing. Two configurations of atrial and ventricular pacing were
      compared: unipolar and bipolar. During unipolar ventricular pacing the
      indifferent electrode (anode) was a high impedance chest pad. For bipolar
      ventricular pacing the indifferent electrode was a ring electrodes placed 2 cm
      proximal to the tip. Unipolar atrial pacing was performed with 1 of 5 proximal
      ring electrodes acting as cathode ("cathodic") or as anode ("anodic") in
      conjunction with a chest pad. Bipolar atrial pacing was performed using
      combinations of 2 of 5 ring electrodes. Atrial capture was obtained in all 55
      subjects attempted. When all electrode combinations were compared, atrial capture
      was significantly more frequent using the bipolar approach (153/210 bipolar,
      65/210 unipolar; t = 7.37, P < 0.001). For unipolar atrial pacing, cathodic
      stimulation (from esophagus) was more successful than anodic stimulation
      (cathodic 62/105, anodic 20/105; t = 5.81, P < 0.001). In 43 subjects attempted
      unipolar ventricular pacing resulted in a higher frequency of capture than the
      bipolar approach (unipolar 41/43 (95.3%), bipolar 19/43 (44.2%); P < 0.001). In
      conclusion, atrial pacing was optimal using pairs of ring electrodes ("bipolar")
      while ventricular pacing was optimal using the distal electrode tip (cathode) in
      conjunction with a chest pad electrode ("unipolar"). This gastroesophageal
      electrode may be useful in the emergency management of acute bradyarrhythmias and
      for elective electrophysiological studies.

PMID- 9249838
TI  - Magnetic resonance imaging and signal-averaged electrocardiography in patients
      with repetitive monomorphic ventricular tachycardia and otherwise normal
      electrocardiogram.
AB  - Early or localized forms of arrhythmogenic right ventricular dysplasia (ARVD)
      have been proposed as the arrhythmogenic substrate of repetitive monomorphic
      ventricular tachycardia (RMVT) originating in the right ventricular outflow tract
      in patients without any underlying cardiac abnormality on clinical examination
      and echocardiography. To further examine this hypothesis, magnetic resonance
      imaging (MRI) and signal-averaged electrocardiography (SAECG) were performed on
      23 patients with RMVT and normal 12-lead standard ECG of conducted sinus beats.
      MRI was performed using ECG-gated turbo spin-echo images of the heart in order to
      detect signs of early or localized forms of ARVD, such as localized wall
      thickness reductions, signal intensity increase indicating adipose tissue
      infiltrates, and regional bulgings or aneurysms. MRI was normal in 22 (96%) of 23
      study patients. In the remaining patient (4%), MRI demonstrated signal intensity
      increase in the intraventricular septum but not in the right ventricular outflow
      tract. Time-domain analysis of the SAECG was normal in 21 (91%) of 23 patients
      and revealed ventricular late potentials in 2 study patients (9%). Frequency
      domain analysis of the SAECG was normal in 22 (96%) of 23 patients and revealed
      ventricular late potentials in one study patient (4%). We conclude that normal
      MRI findings of the heart and absence of ventricular late potentials in the SAECG
      in most patients with RMVT and otherwise normal ECG do not support the hypothesis
      that early or localized forms of ARVD create the arrhythmogenic substrate in the
      majority of these patients.

PMID- 9249839
TI  - Acute radiation dermatitis following radiofrequency catheter ablation of
      atrioventricular nodal reentrant tachycardia.
AB  - Radiation exposure during fluoroscopic imaging poses potential risks to patients
      and physicians, especially during protracted cardiovascular or radiological
      interventional procedures. We describe a woman with refractory paroxysmal
      supraventricular tachycardia who underwent radiofrequency catheter ablation of
      the slow pathway involved in atrioventricular nodal reentrant tachycardia. The
      patient subsequently returned 4 weeks later with acute radiation dermatitis that
      was retrospectively attributed to a malfunction in the fluoroscopy unit that
      lacked a maximum current output cut-off switch. Using dose reconstruction studies
      and her estimated biological response, we determined that she received between 15
      and 20 Gy (1 Gy = 100 rads) to the skin on her back during the procedure. The
      exposure will result in an increase in her lifelong risk of skin and lung cancer.
      This article underscores the potential for radiation-induced injury during
      lengthy therapeutic procedures using x-ray equipment.

PMID- 9249840
TI  - Can catheter ablation in cardiac arrest survivors prevent ventricular
      fibrillation recurrence?
AB  - Ventricular tachyarrhythmias are the most common cause for sudden cardiac death.
      The success of catheter ablation for supraventricular tachycardias led to the
      supposition that ablation could also be used in the treatment of ventricular
      tachycardias. Despite the promising results in bundle branch reentry and some
      forms of idiopathic ventricular tachycardia, the success rate in patients with
      coronary artery disease is still low. There is hope that new approaches to
      reliably localize the critical region of the tachycardia and new ablation
      techniques to create larger areas of injury may lead to a wider application of
      ablation therapy in the treatment of ventricular tachycardia. Survivors of
      cardiac arrest typically have more rapid and unstable arrhythmias than patients
      with sustained ventricular tachycardia, and these rapid arrhythmias frequently
      degenerate into ventricular fibrillation. The instability of the arrhythmia makes
      it impossible to localize the arrhythmia origin with current mapping techniques.
      Experimental and clinical data, however, suggest that these arrhythmias also
      frequently start from a localized area of electrical activation. With
      developments in mapping techniques and energy delivery, catheter ablation may
      soon become a feasible therapeutic approach in some patients with unstable
      arrhythmias. The article discusses the prerequisites for this approach and
      suggests the patients who may be appropriate candidates for this technique.

PMID- 9249841
TI  - Appointment scheduling on computer.
AB  - The program is well-written, intuitive, and easy to use once initial data, such
      as the available appointment slots, has been entered. While the effort may not
      seem worthwhile initially, the ability to access an office appointment book from
      several locations simultaneously and the reporting capabilities of the software
      make MEDSched a useful addition to any busy office practice or clinic. Please
      send your comments and suggestions to me at adm4@columbia.edu.

PMID- 9249842
TI  - Biomaterials unavailability threatens medical devices.

PMID- 9249843
TI  - Sustained wide complex tachycardia resulting in myocardial injury in a patient
      with apical hypertrophic cardiomyopathy.

PMID- 9249844
TI  - Right atrial separation procedure for eliminating chronic atrial fibrillation
      associated with atrial septal defect.
AB  - Chronic atrial fibrillation (AF) had been documented in a patient with atrial
      septal defect for 7 years. A right atrial separation procedure was performed for
      ablation of chronic AF, concomitant with repair of the atrial septal defect, and
      followed by atrial electrophysiological mapping. A horizontal transectional
      incision extending to the borders of the atrial septum and the tricuspid annulus
      was made. Cryolesions of the atrial isthmus between the margin of the upper
      incision and the tricuspid valve annulus were created at -60 degrees C for 2
      minutes at a time. After the operation, the patient had restored normal sinus
      rhythm during a subsequent follow-up period of 48 months.

PMID- 9249845
TI  - Chronic left main coronary artery occlusion: a complication of radiofrequency
      ablation of idiopathic left ventricular tachycardia.
AB  - We describe in this report the development of chronic left main coronary artery
      (LMCA) occlusion in a young patient 2 years after an uncomplicated, successful
      ablation of idiopathic left ventricular tachycardia. This complication appears to
      be a late consequence of trauma to the LMCA during the procedure rather than an
      acute or subacute embolic event.

PMID- 9249846
TI  - Right atrial appendage to right ventricle accessory atrioventricular connection:
      a case report.
AB  - Atrial and ventricular attachments of accessory atrioventricular connections have
      classically been localized to adjacent atrial and ventricular tissues, and this
      principle is responsible for the widespread success of radiofrequency catheter
      ablation. We present anatomical evidence of an unusually located accessory
      atrioventricular connection, which bridged the atrioventricular ring
      epicardially, directly from the base of the right atrial appendage to the right
      ventricle. This observation might offer a new insight into unusual accessory
      atrioventricular connection locations and may explain why some endocardial
      radiofrequency catheter ablation procedures might fail.

PMID- 9249847
TI  - Iatrogenically induced intractable atrioventricular reentrant tachycardia after
      verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome
      and idiopathic dilated cardiomyopathy.
AB  - In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable
      atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS
      without preexcitation, caused by junctional escape beats after verapamil or
      unidirectional antegrade block of accessory pathway after catheter ablation,
      established frequent AVRT attack.

PMID- 9249848
TI  - Mode switching anomalies: a patient who remained symptomatic during paroxysmal
      atrial tachyarrhythmias despite a mode switching pacemaker.
AB  - A patient with an automatic mode switching pacemaker continued to experience
      discomfort during the onset of paroxysmal supraventricular tachyarrhythmias.
      Investigation revealed that the patient was sensing abrupt rate changes as the
      ventricular paced rate tracked the tachycardia during onset and detection phases.
      Her pacemaker was replaced with a new device with both mode switching and rate
      smoothing capabilities with resultant elimination of symptoms.

PMID- 9249849
TI  - Alternating current electrocution detection and termination by an implantable
      cardioverter defibrillator.
AB  - A patient with an ICD accidentally grasped a power line and was electrocuted. He
      was unable to release the cable during electrocution though he remained
      conscious. After receiving a shock from his ICD, the powerline was released. ICD
      interrogation revealed inappropriate detection of alternating current and
      delivery of a shock.

PMID- 9249850
TI  - Comparing the performance of the Unity VDD and Thera VDD pacing systems.

PMID- 9249851
TI  - Cost effectiveness in health care.

PMID- 9249852
TI  - Atrial fibrillation and dilated cardiomyopathy.

PMID- 9249853
TI  - The Gottingen minipig in pharmacology and toxicology.
AB  - Pigs traditionally are used in surgical and physiological research. Since the
      development of the Minnesota minipig in 1949 at the Hormel Institute (USA),
      miniature pigs have been introduced as a model in pharmacology and toxicology,
      because of scientific, economic and ethical reasons.

PMID- 9249854
TI  - Nutrition of (Gottingen) minipigs: facts, assumptions and mysteries.
AB  - Detailed guidelines are available concerning the nutrient requirements of pigs
      (National Research Council 1988). These nutrient requirements are based on ad
      libitum feeding and obtaining maximum growth, as they have originated from
      feeding schedules for slaughter pigs. Whether these nutrient guidelines for pigs
      can be applied to minipigs as well remains to be answered. Moreover, ad libitum
      feeding and maximum growth are not considered the optimum in scientific research.
      The German Society for Laboratory Animal Science has published guidelines for the
      composition of minipig diets, mainly based on empirical results (1993). Upon
      comparison of dietary guidelines for pigs and minipigs, differences can be found.
      At the moment it is unclear which of the two dietary guidelines guarantees that
      all minimum nutrient requirements of the minipig are met. Restricted feeding is
      often applied in studies using minipigs, in order to prevent obesity. As the two
      guidelines are based on ad libitum feeding, this raises the question whether
      restriction results in (marginal) nutrient deficiencies, which may interfere with
      experimental results.

PMID- 9249855
TI  - Health status of experimental pigs.
AB  - Due to the increase in the use of pigs in research, there seems to be a demand
      from the scientific community for an improved quality of experimental pigs. Germ
      free pigs may be produced by removing fully developed foetuses aseptically from
      the uterus by hysterectomy and rearing them in isolators, alternatively embryo
      transfer may be used. Such rederived pigs may be maintained in isolators in the
      gnotobiotic status or gnotobiotic pigs may be used for the upstart of a breeding
      colony housed under conditions (i.e. a barrier) protecting them against certain
      agents, for which a monitoring system is operated. Different categories of
      barrier-bred pigs, such as, minimal disease, specific pathogen-free and
      microbiologically defined, are presented and differences between these categories
      are discussed. Basic principles of health monitoring in pigs, e.g. sample size,
      testing frequency and methods, are outlined. It is discussed how the lack of
      positive findings in health monitoring may be due to other factors than freedom
      from infection, e.g. treatment with antibiotics or a statistically invalid
      examination. Finally, the risk of infection with certain porcine agents when
      housing barrier-bred pigs in conventional experimental units is discussed.

PMID- 9249856
TI  - How clean is a mini-pig?--Impressions and suggestions of a pathologist working in
      the field of toxicology.
AB  - Gross and histopathological investigations of more than 100 minipigs revealed: 1.
      Findings due to repeated blood sampling. For anatomical reasons the thyroid gland
      of pigs can be injured during blood sampling. Histopathological investigation of
      thyroid glands often revealed inflammatory and reparative fibrotic changes of
      this organ. Depending on the grade of damage, thyroid hormone levels may vary. To
      avoid misinterpretation of results, most careful blood sampling by experienced
      personnel is recommended. 2. Findings due to viral, bacterial and parasitic
      infections. These concerned mainly the lungs which often showed pneumonic
      alterations. In case of parasitic invasion, the skeletal muscles may reveal
      degenerative changes due to sarcosporidia (re-) infection. Therefore, optimal
      hygienic conditions, e.g. during blood sampling, and continuing health monitoring
      are recommended. 3. Findings due to preventive iron administration. Months after
      preventive iron-dextran administration at the breeding station, histopathological
      examination revealed siderin accumulation in a number of organs, namely in the
      cells of the mononuclear phagocytic system in liver and kidneys. As a unique
      finding an intraglomerular siderin deposition in the mesangial cells with
      subsequent glomerulosclerosis in certain glomeruli was observed.

PMID- 9249857
TI  - Anaesthesia and basic experimental surgery of minipigs. A practical exercise.
AB  - Minipigs tolerate anaesthesia very well. The only disadvantages are the
      difficulties in performing venous puncture and endotracheal intubation. To
      overcome these the animals should be well sedated prior to induction by
      intravenous injection, and deeply anaesthetized prior to the introduction of the
      endotracheal tube. Anaesthetic regimen and several basic experimental surgical
      techniques will be practised.

PMID- 9249858
TI  - Characterization of the P450 system in Gottingen minipigs.
AB  - It is essential to establish the activity and regulation of the cytochrome P450
      system of species selected for toxicological and pharmacological studies. The
      minipig has become a popular substitute for the traditional non-rodent species
      although little information is available on its P450 system. The total P450 and
      the enzyme activity of the most important drug-metabolizing isoenzymes: CYP1A2,
      CYP2C19, CYP2D6, CYP2E1 and CYP3A4 were measured in liver microsomes from 4
      minipigs and 8 conventional pigs of both sexes. Immunochemical levels were
      determined for 4 of teh isoenzymes. The total P450 activity was slightly higher
      in minipigs compared to conventional pigs but no sex difference was detected.
      CYP1A2 activity (7-ethoxyresorufin) was 4 times higher in female minipigs than in
      male minipigs. The activity in male minipigs was almost identical to the activity
      in conventional pigs. The activity of CYP2E1 (chlorzoxazone) was 4 times higher
      in female than in male minipigs and 2 times higher in female than in male
      conventional pigs. No activity of CYP2D6 (debrisoquine) and CYP2C19 (mephenytoin)
      could be detected. The CYP3A4 activity (testosterone) detected in minipigs was
      higher than the activity in conventional pigs. A weak sex difference was seen in
      both strains. Western blotting using anti-human CYP2E1 and CYP3A4 confirmed the
      results obtained in the enzyme activity assays, while only CYP1A2 correlated with
      the activity in the conventional strain. The total P450 enzyme activity was close
      to the levels reported for human beings, as were the activities of CYP2E1 and
      CYP3A4.

PMID- 9249859
TI  - The HELLP syndrome: its association with unexplained elevation of MSAFP and MShCG
      in the second trimester.
AB  - In this study, we examined the relationship between concentrations of maternal
      serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin
      (MShCG) in the second trimester and the haemolysis, elevated liver enzymes, low
      platelet count (HELLP) syndrome. The concentrations of both serum markers,
      expressed in multiples of the median (MOM), in 16 women with the HELLP syndrome
      were compared with those in 10443 women without this syndrome who were screened
      for Down's syndrome and neural tube defects. All the women with a singleton
      pregnancy and a known pregnancy outcome were included in this study. At a cut-off
      level of 2.5 MOM, 37.5 per cent of the pregnancies with the HELLP syndrome had an
      elevated MShCG level, compared with 4.8 per cent in the whole population (P <
      0.0001). 12.5 per cent of the women with the HELLP syndrome had an elevated MSAFP
      level, compared with 1.3 per cent in the whole population (P < 0.025). Women with
      a combined elevation of MSAFP and MShCG levels (0.3 per cent of the screened
      population) had a 47 time greater risk of developing the HELLP syndrome than the
      others (P < 0.01). The HELLP syndrome should be taken into account in the case of
      unexplained elevated levels of MShCG and MSAFP, especially in the rare event of
      combined elevation of both markers.

PMID- 9249860
TI  - Comparison of 12 assays for detecting hCG and related molecules in urine samples
      from Down syndrome pregnancies.
AB  - Urine is a new medium for Down syndrome testing. In an effort to determine the
      best type of human chorionic gonadotropin (hCG)-related immunoassay for urine
      testing, we examined 14 Down syndrome and 91 unaffected pregnancy urine samples
      with 12 established assays. The assays included (a) those that detect hCG beta
      core fragment only; (b) those that detect beta-core fragment with less than 18
      per cent free beta-subunit cross-reactivity; (c) that which equally detects free
      beta-subunit and beta-core fragment; and (d) those that detect hCG, free beta
      subunit, or combinations thereof. The seven type a and b assays had the highest
      sensitivity for Down syndrome. The median MOM for Down syndrome was 5.93 (range
      4.73-7.53). At a 10 per cent false-positive rate, the median observed detection
      rate was 93 per cent (range 79-100 per cent) and the median predicted detection
      rate was 85 per cent (range 69-96 per cent). The assays that did not mainly
      detect beta-core fragment (types c and d) had poorer screening performance. The
      median MOM for Down syndrome was 2.70 (range 2.16-3.63 MOM). At a 10 per cent
      false-positive rate, the median observed detection rate was 50 per cent (range 36
      64 per cent) and the median predicted detection rate was 37 per cent (range 21-62
      per cent). We infer that the assays that only detect beta-core fragment, or beta
      core fragment with minor free beta-subunit cross-reactivity (types a and b), are
      the better urine-based tests for Down syndrome screening.

PMID- 9249862
TI  - The influence of prenatal ultrasound on the prevalence of congenital anomalies at
      birth.
AB  - The objectives of the study were (1) to assess whether prenatal ultrasound
      examinations affected the prevalence of congenital anomalies at birth and the
      incidence of terminations of pregnancy for fetal anomalies and (2) to examine the
      detection rate of the main fetal anomalies. We studied all births and stillbirths
      with congenital defects, and all terminations of pregnancy for fetal anomalies in
      the Rambam Medical Center during a 5-year period (1989-1993) and correlated them
      to ultrasound findings. There were 23439 births during the study period. The
      incidence of newborns with anomalies decreased from 1.95 to 1.34 per cent (P <
      0.01). The incidence of termination of pregnancy because of fetal anomalies
      increased from 0.35 to 0.83 per cent (P < 0.003) and the detection rate of
      malformations increased from 53.94 to 79.60 per cent (P < 0.001). It is concluded
      that terminations of pregnancy after ultrasound detection of fetal anomalies had
      an impact on the prevalence of anomalies in newborns. There was also continuing
      significant improvement in the detection rate of ultrasound examinations.

PMID- 9249861
TI  - The effect of differences in the distribution of maternal age in England and
      Wales on the performance of prenatal screening for Down's syndrome.
AB  - We aimed to determine how differences in the age at which women had their
      pregnancies influenced the expected detection and false-positive rates of serum
      screening for Down's syndrome (i) between 1970 and 1993 in England and Wales, and
      (ii) between regions and districts of England and Wales in 1991. We applied
      published estimates of Down's syndrome screening to regional and district data on
      the age distribution of maternities and changes in the age distribution over time
      in England and Wales obtained from the Office of Population Censuses and Surveys.
      From 1970 to 1993 women, on average, became pregnant at an older age; the
      percentage of maternities among women aged 35 or more increased from 7 to 9.2 per
      cent. This was not a great enough change to have had a material effect on the
      performance of Down's syndrome screening. In 1991, the percentage of maternities
      among women aged 35 or more varied from 5 to 20 per cent among Health Districts,
      a difference that would influence the performance of screening; for example,
      using the triple test and a risk cut-off of 1 in 250, the detection rates would
      have varied from about 55 to 70 per cent and the false-positive rates from 4.4 to
      8.8 per cent across different districts. The tendency for women to have their
      pregnancies at an older age would have had a negligible impact on the performance
      of serum screening for Down's syndrome, but differences in the age when women had
      their pregnancies in different parts of the country would lead to twice as many
      women being referred for amniocentesis in some districts than in others when
      offered the same method of serum screening and at the same risk cut-off level.
      The results will have important implications for the local purchasers of Down's
      syndrome screening services.

PMID- 9249863
TI  - Tracheal obstruction in experimental diaphragmatic hernia: an endoscopic approach
      in the fetal lamb.
AB  - Congenital diaphragmatic hernia (CDH) is associated with a neonatal mortality of
      up to 50 per cent resulting from pulmonary hypoplasia. Experimental ligation of
      the trachea increases pulmonary growth in fetuses with experimental diaphragmatic
      hernia (EDH). To provide a potentially reversible tracheal occlusion (TO) using a
      minimally invasive procedure, we designed the endoscopic placement of a latex
      tracheal balloon in fetal lambs with EDH. Following surgical creation of a left
      EDH at 85 days' gestation, endoscopic occlusion of the fetal trachea was
      performed at 120 days. The fetuses were retrieved at 139 days. The procedure was
      successful in 5/11 attempts, resulting in liveborns in which the balloon occluded
      the trachea completely with expanded lungs and reduction of the herniated viscera
      into the abdomen. These cases were compared with five cases of EDH without TO and
      six controls. In the TO group, the lung weight was significantly greater but the
      radial alveolar count, DNA content, and protein content were similar to normal
      controls. All lung growth parameters were greater in the TO than in the EDH
      group. Occlusion of the trachea using an endoscopic technique could provide a
      useful alternative to open fetal surgery in fetuses with CDH.

PMID- 9249864
TI  - Quantitative evaluation of fluorescence in situ hybridization (FISH) signals in
      uncultured coelomic cells.
AB  - Uncultured coelomic cells were hybridized with alpha satellite DNA probes
      representing chromosomes X, Y, 18, and 13/21 in order to evaluate the
      distribution of hybridization signals obtained by fluorescence in situ
      hybridization (FISH) analysis of this cell type. Cells from 26 samples were
      hybridized with the X probe and the Y probe was hybridized with cells from 25 of
      the samples. Cells from 16 and 11 samples were hybridized with an 18 alpha
      satellite DNA probe and 13/21 alpha satellite probe, respectively. The evaluation
      demonstrated that FISH with X, Y, 18, and 13/21 alpha satellite DNA probes on
      uncultured coelomic cells is a reliable technique since the distribution of
      hybridization signals is comparable to that seen in uncultured amniotic fluid
      cells.

PMID- 9249866
TI  - ALDP expression in fetal cells and its application in prenatal diagnosis of X
      linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is due to an impairment in the peroxisomal
      beta-oxidation of very long straight chain fatty acids (VLCFAs) and the gene
      involved encodes a 75 kD protein (ALDP). Prenatal diagnosis is usually made by
      measurement of VLCFAs in cultured amniotic fluid cells (CAF) and chorionic villus
      cells (CCV), but some misdiagnoses have been reported. For this reason, some
      authors suggest the use of more than one strategy to minimize the risk of
      pitfalls. In this study we show, by immunochemical techniques, that ALDP is
      expressed in chorionic villi and amniotic cells and can be used for prenatal
      diagnosis of X-ALD in kindreds where ALDP is absent (69-84 per cent), together
      with VLCFA determination. Moreover, we demonstrate that the culture medium
      modifies ALDP expression; therefore, it is a factor that must be taken into
      account when a prenatal diagnosis is done.

PMID- 9249865
TI  - Fetal nucleated erythrocytes (NRBCs) in chorionic villus sample supernatant
      fluids: an additional source of fetal material for karyotype confirmation.
AB  - Fetal erythrocytes leak from the fetal capillaries at the time of chorionic
      villus removal. The purpose of this study was to determine if fetal nucleated
      erythrocytes (NRBCs) could be isolated from the chorionic villus sampling (CVS)
      supernatant fluid and used as an additional source of fetal material in order to
      confirm the fetal karyotype in cases of CVS mosaicism. One hundred CVS
      supernatant fluids were studied by simultaneous immunophenotyping, using a mouse
      antifetal haemoglobin antibody, UCH gamma, combined with fluorescent in situ
      hybridization (FISH) analysis using X- and Y-specific DNA probes. A chromosome 18
      probe was also used in the case of a known male fetus with trisomy 18. Fetal
      haemoglobin (HbF)-positive cells were identified in 73 supernatant fluids and HbF
      positive nucleated cells were present in 60 samples. The number of cells detected
      per sample showed great variation among the individual samples. FISH analysis was
      performed in 41 cases. FISH prediction of the fetal gender was concordant with
      the CVS karyotype in all cases, and the fetal trisomy 18 was correctly verified.
      In five cases in which Y sequences were detected, a small number of HbF-positive
      cells with two X signals were also identified; interestingly, in three of the
      five cases, the mother was a beta-thalassaemia carrier. This technique can be
      used as a quick and accurate method for the immediate verification of CVS results
      in cases of mosaicism, thus avoiding second-trimester amniocentesis.

PMID- 9249868
TI  - A report of recurrent anencephaly with trisomy 2p23-2pter: additional evidence
      for the involvement of 2p24 in neural tube development and evaluation of the role
      for cytogenetic analysis.
AB  - A woman carrying a balanced reciprocal translocation, 46,XX,t(2;5)(p23;p15)pat,
      was ascertained following the delivery of an anencephalic fetus whose karyotype
      was 46,XY,5p+. She subsequently had two pregnancies with a similar unbalanced
      karyotype (trisomy 2p23-2pter and monosomy 5p15-5pter), one of which was also
      anencephalic. She has three living children, two of whom are balanced
      translocation carriers. This history raises questions regarding the necessity of
      cytogenetic assessment of cases identified by ultrasound with 'isolated' neural
      tube defects. The observation of duplication of the 2p23-2pter region in
      conjunction with anencephaly also adds to the growing body of evidence suggesting
      an association of this region and neural tube development.

PMID- 9249867
TI  - Molecular analysis of the insulin receptor gene for prenatal diagnosis of
      leprechaunism in two families.
AB  - Leprechaunism is a rare autosomal recessive disorder characterized by marked
      intrauterine and postnatal growth retardation, severe insulin resistance, and
      altered glucose homeostasis. This syndrome is related to mutations in the insulin
      receptor (IR) gene that impair the transmission of the insulin signal by several
      mechanisms. There is no effective therapy and patients usually die within the
      first months of life. Here we report the prenatal diagnosis of leprechaunism in
      two unrelated families in which affected children were compound heterozygotes
      with two different deficient IR alleles. In family Par-1, the disease IR alleles
      carried a missense mutation located in exon 18 (Arg1092-->Trp) and exon 20
      (Glu1179-->Lys). In family Als, a 3-basepair deletion causing the loss of Asn281
      in exon 3 and a major deletion of exons 10-13 were present in the maternal and
      paternal mutant IR alleles, respectively. Prenatal diagnosis was made in each
      family by a specific approach combining denaturing gradient gel electrophoresis
      (DGGE) and Southern blotting. This methodology allowed us to correctly predict
      the genotype of the two fetuses at the IR locus.

PMID- 9249869
TI  - Diagnosis of fetal anomalies by three-dimensional imaging using helical computed
      tomography.
AB  - We present the first report on the use of helical computed tomography (CT), a
      new, non-invasive diagnostic technique that produces three-dimensional (3-D)
      images, in prenatal diagnosis. This technique was used to construct 3-D images in
      the prenatal diagnosis of two anomalous fetuses. The 3-D images provided clear
      information about the anomalies: trisomy 18 in one case and cystic hygroma in the
      other. In one case, rapid intervention after a planned Caesarean section
      prevented respiratory distress. Surgery to correct the anomaly was performed 2
      days postnatally; the infant recovered uneventfully.

PMID- 9249870
TI  - Prenatal diagnosis of partial trisomy 12 and partial trisomy 21 due to a 3:1
      segregation of maternal reciprocal translocation t(12;21) (p13.3;q21).
AB  - We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12
      (p13.3-pter) and partial trisomy 21 (pter-q21) due to a 3:1 segregation with
      tertiary aneuploidy transmitted from a maternal reciprocal translocation 12;21.
      Genetic amniocentesis of a 39-year-old gravida 2, para 1 woman at 19 weeks'
      gestation due to advanced maternal age revealed an unusual karyotype of
      47,XY,+der(21)t(12;21)(p13.3;q21)mat. The pregnancy was terminated at 24
      gestational weeks. The proband postnatally displayed by dysmorphic features of a
      round flat face with prominent cheeks and high forehead, upward slanting
      palpebral fissures, epicanthic folds, hypertelorism, a short nose, a broad and
      depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth,
      thin upper vermilion and broad everted lower lip, low-set ears with prominent
      anthelix and deep concha, broad hands with simian creases, a short neck, and
      cryptorchidism. The association of the involved chromosomal segments with the
      phenotype of Down's syndrome and trisomy 12p syndrome is discussed.

PMID- 9249871
TI  - Prenatal diagnosis for inborn errors of metabolism and haemoglobinopathies: the
      Montreal Children's Hospital experience.
AB  - We reviewed all referrals for prenatal diagnosis for inborn errors of metabolism
      and haemoglobinopathies performed at the Montreal Children's Hospital Prenatal
      Diagnosis Centre/McGill University during the period 1990-1995; 92 procedures
      were performed for these indications (less than 1 per cent of all referrals for
      prenatal diagnosis). All prenatal diagnoses for haemoglobinopathies (n = 55) were
      exclusively DNA-based. The three most frequent referrals were for beta
      thalassaemia, sickle cell anaemia, and Tay-Sachs disease, accounting for 68 per
      cent of cases; the other indications were predominantly for untreatable inborn
      errors of metabolism. Our unit maintains population-based carrier screening
      programmes in high schools for beta-thalassaemia and Tay-Sachs diseases. Carriers
      detected in these programmes accounted for the majority of referrals for these
      two conditions. This study indicates that carrier testing and screening for
      sickle cell anaemia may be also welcomed by at-risk groups in Quebec.

PMID- 9249872
TI  - Immature mesenteric teratoma in a male newborn infant: prenatal ultrasonographic
      diagnosis and surgical treatment.
AB  - A very rare case of mesenteric teratoma, detected by routine ultrasound screening
      at 20 weeks' gestation, is reported. The patient, a male newborn delivered at 40
      weeks' gestation in good condition, was successfully operated on at birth. The
      post-operative course was regular and the baby is currently doing well.

PMID- 9249874
TI  - Current awareness in prenatal diagnosis.

PMID- 9249873
TI  - Confined placental mosaicism for trisomy 2 with intrauterine growth retardation
      and severe oligohydramnios in the absence of uniparental disomy in the fetus.

PMID- 9249875
TI  - p53 gene mutations are rare in patients but common in patient-originating cell
      lines in multiple myeloma.
AB  - We have shown previously that detectable serum concentration of p53 protein is
      associated with poor prognosis in multiple myeloma (MM). In this study, we
      studied p53 gene mutations in 29 bone marrow samples of MM patients using
      polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and
      direct sequencing. No p53 mutations were found in these patients although 41% of
      the patients had an elevated serum p53 protein concentration. This result
      indicates that the detectable serum level of p53 protein is not associated with
      p53 mutations. In addition, we have also analysed three MM cell lines established
      from bone marrow samples. All the cell lines contained p53 mutations in exon 5.
      However, bone marrow samples of the patients associated with the cell lines did
      not have these mutations at the time of diagnosis, nor did the original samples
      which were used to establish the cell lines. This indicates that p53 mutations
      can arise during the cell passages.

PMID- 9249876
TI  - Comparison of a semi-automated new Coulter methylene blue method with
      fluorescence flow cytometry in reticulocyte counting.
AB  - A semi-automated new methylene blue method for reticulocyte counting was compared
      to the manual method and fluorescence flow cytometry. Over a wide range of
      reticulocyte counts (0.3-12.7%) the new methylene blue method was found to be
      comparable to that of fluorescence flow cytometry, with high precision. Between
      run precision studies showed coefficients of variation (CVs) of 4.8, 6.9 and
      14.5% for reticulocyte counts of 9.5, 2.4 and 0.7%, respectively. Within-run
      precision studies showed CVs of 8.6, 8.1 and 6.1% for reticulocyte counts of 0.9,
      5.3, and 18.4%, respectively. The correlation coefficient between the Coulter
      method and the manual method was 0.83, and 0.85 between the Coulter method and
      flow cytometry. The possibility of extending the incubation time to at least 4 h
      and the insignificant changes observed with samples stored for up to at least 72
      h at 4-8 degrees C make this new method most convenient and allow any laboratory
      having Coulter STKS or MAXM cell counters to perform reticulocyte counts in an
      efficient, reliable manner.

PMID- 9249877
TI  - Serum aminoterminal propeptide of type III procollagen (S-PIIINP) and
      hepatobiliary dysfunction in patients with ulcerative colitis.
AB  - The aim of the study was to estimate the usefulness of measuring the circulating
      concentration of serum aminoterminal propeptide of type III collagen (S-PIIINP)
      in screening for hepatobiliary diseases in patients with ulcerative colitis. S
      PIIINP was measured in 69 patients with ulcerative colitis and normal liver
      biochemistry, in 14 patients with ulcerative colitis and elevated catalytic
      concentration of alkaline phosphatases in serum (S-ALP, EC 3.1.3.1) but without
      primary sclerosing cholangitis (PSC), and in 20 patients with ulcerative colitis
      and PSC. The median S-PIIINP was 3.1 micrograms l-1 in patients with ulcerative
      colitis and normal liver biochemistry, 4.3 micrograms l-1 in patients with
      ulcerative colitis and hepatobiliary disorder other than PSC and 8.9 micrograms l
      1 in those with ulcerative colitis and PSC. When the S-PIIINP cut-off level was
      set at 5.0 micrograms l-1, 1% of the patients with ulcerative colitis and normal
      liver biochemistry, 21% of those with hepatobiliary disorder, not PSC, and 90% of
      the patients with PSC had S-PIIINP values above that concentration. In
      conclusion, S-PIIINP above 5.0 micrograms l-1 in a patient with ulcerative
      colitis strongly suggests concomitant PSC.

PMID- 9249878
TI  - beta-Glucuronidase in common duct bile, methodological aspects, variation of pH
      optima and relation to gallstones.
AB  - beta-Glucuronidase of human or bacterial origin may deconjugate bilirubin
      diglucuronide, causing pigment gallstones. Intrinsic interference by biliary
      compounds must be minimized for accurate assay of beta-glucuronidase. We report a
      modified ion-pair extraction of interfering substances by tetrahexylammonium
      chloride (THAC) in ethyl acetate in the presence of albumin, and a microtitre
      plate assay for biliary beta-glucuronidase activity in bile with the substrate p
      nitrophenol-glucuronide. Adding albumin improved the recovery of beta
      glucuronidase activity to 99.8% (CV 1.9%), and 92.2% of the bilirubin in bile
      samples was extracted in one step. Competitive inhibition was overcome by
      increasing the substrate concentration. In endoscopically obtained common duct
      bile from 44 patients, five different beta-glucuronidase activity peaks were
      identified, at pH 3.9, 4.8, 5.3, 5.8 and 7.2. The pH profiles were classified
      into one bacterial pattern and five patterns for presumed human beta
      glucuronidase. Of the latter patterns, four displayed dual activity peaks. In a
      second sample, obtained at follow up in four patients, their original pH profile
      was maintained. In conclusion, using the modified purification and assay system,
      we found functionally diverse subcategories of human beta-glucuronidase with
      respect to activity at variable pH. Our results indicate that several pH optima
      have to be taken into consideration in order to clarify the role of human biliary
      beta-glucuronidase in the pathogenesis of pigment gallstones. Bacterial beta
      glucuronidase activity was associated with duodenal diverticula (p < 0.05) and
      common duct stones (p < 0.05).

PMID- 9249879
TI  - Relation between blood pH and ionized calcium during acute metabolic alteration
      of the acid-base balance in vivo.
AB  - We induced metabolic alkalosis and acidosis in 10 healthy volunteers in order to
      analyse in vivo relation between pH and ionized calcium (cCa2+). In the
      alkalinization test, 2.7 mol/kg NaHCO3 was injected. In the acidification test,
      volunteers took 4 mmol/kg NH4Cl. Blood pH and cCa2+ (mmol/l) mean values (SD)
      baseline, after alkalinization and acidification tests, were: 7.363 (0.018),
      7.456 (0.031), 7.244 (0.031), 1.27 (0.03), 1.14 (0.03) and 1.38 (0.04). Mean
      slope of regression log cCa2+/pH was -0.39 (SD 0.11). Such a slope differs after
      in vivo or in vitro changes, due to the in vivo rapid restoration of equilibrium
      between the plasmatic and interstitial compartments following changes in water
      and electrolyte concentrations. The type of acid-base alteration-respiratory or
      metabolic-influences pH changes, and consequently the regression slope. The in
      vivo slope for log cCa2+/pH in normal subjects (-0.21) is much the same as in
      acute respiratory alterations (-0.17), whereas it differs in acute metabolic
      alterations (present study). Bicarbonates play different roles: the same changes
      in pH cause greater changes in cCa2+ after acute metabolic rather than
      respiratory alterations. Ca2+ homeostasis is maintained in acute respiratory acid
      base imbalance, despite wide shifts in pH, whereas in acute metabolic alterations
      even small pH changes have striking repercussions on cCa2+. The experimental
      angular coefficient for in vivo acute metabolic acid-base alterations differs
      from the theoretical one calculated by Thode's differential equation (-0.25).

PMID- 9249880
TI  - Low density lipoprotein catabolism is enhanced by the cleaved form of alpha-1
      antitrypsin.
AB  - The frequent occurrence of hypocholesterolaemia following inflammatory processes
      is well known but unexplained. Elevated plasma levels of serine proteinase
      inhibitors (serpins) and their complexes with target enzymes have been
      demonstrated in inflammatory, malignant and infectious diseases which are also
      often accompanied by low plasma cholesterol levels. Under inflammatory
      conditions, uncomplexed, but cleaved inactive serpins arising from slow
      deacylation of the serpin-proteinase complex may be present in the circulation.
      To determine the influence of native and cleaved forms of serpins, such as alpha
      1-antitrypsin (AAT), on lipoprotein metabolism, we investigated the effect of
      these forms on low density lipoprotein (LDL) catabolism in human HepG2 cell line.
      We have found that the cleaved form of AAT in concentrations from 125 to 2000
      nmol l-1 stimulates LDL binding to the HepG2 cells, by up to 49% with a
      subsequent increase in LDL uptake and degradation of up to 79 and 65%
      respectively. Native AAT was also found to increase LDL binding and
      internalization by 20-25%, independently of the amount of AAT added, an effect
      most probably due to the cleaved form of AAT produced by local proteolysis of
      native AAT incubated in the cell culture. Moreover we have shown that the cleaved
      form of AAT interacts with LDL in vitro, and that such an interaction abolishes
      AAT ability to stimulate LDL binding and internalization. This study for the
      first time describes the ability of the cleaved form of AAT to stimulate LDL
      binding and internalization in HepG2 cell culture, and provides evidence that
      hypocholesterolaemia occurring during inflammatory processes may be mediated by
      cleaved forms of serpins.

PMID- 9249881
TI  - Effect of bilirubin on erythrocyte shape and haemolysis, under hypotonic,
      aggregating or non-aggregating conditions, and correlation with cell age.
AB  - The effect of unconjugated bilirubin on the morphology and haemolysis of human
      erythrocytes was accomplished under distinct incubation conditions: (i) hypotonic
      medium, with bilirubin concentrations ranging from 1 x 10(-9) to 1 x 10(-4) mol l
      1; (ii) isotonic medium, with 171 mumol l-1 bilirubin, in the absence of albumin
      (aggregating conditions), using non-separated and age-fractionated erythrocytes;
      (iii) isotonic medium, with 171 mumol l-1 bilirubin, in the presence of a surplus
      of human serum albumin (non-aggregating conditions), and using sulfisoxazole as a
      bilirubin displacer (bilirubin/albumin and sulfisoxazole/ albumin molar ratios of
      0.5 and 4.0, respectively). Our data showed that low concentrations of bilirubin
      (1 x 10(-7) to 1 x 10(-5) mol l-1) protect against hypotonic haemolysis and
      induce crenation, while higher bilirubin concentrations induce haemolysis and
      lead to membrane disruption. When aggregating conditions were used, these
      phenomena were reproduced, the younger cells being significantly more susceptible
      to crenation while the older erythrocytes showed increased susceptibility to
      haemolysis. In non-aggregating conditions, haemolysis was virtually absent,
      though crenation was evident. Based on the above observations we conclude that
      the first step of erythrocyte bilirubin toxicity is crenation due to an expansion
      of the outer membrane leaflet by bilirubin mono-anion location. This effect is
      more evident in younger cells and explains the protection against the hypotonic
      haemolysis. Insertion of bilirubin deeper into the bilayer, facilitated by higher
      concentrations (> or = 1 x 10(-4) mol l-1) and cell age, produces an unstable
      situation, where bilirubin acid aggregation is apparently the main cause for
      haemolysis and cell destruction.

PMID- 9249882
TI  - A single measurement of biochemical markers of bone turnover has limited utility
      in the individual person.
AB  - Biochemical markers of bone turnover are used to estimate the rate of bone loss
      in the individual osteoporotic patient. During recent years it has become
      increasingly clear that the biological variability of biochemical bone markers
      has to be taken into consideration in the evaluation of their usefulness in the
      clinical setting. Eleven premenopausal, 8 perimenopausal and 11 postmenopausal
      healthy women were included. We assessed the analytical and the biological
      components of variation for a number of resorptive and formative bone markers: u
      hydroxyproline, u-pyridinoline, and u-deoxypyridinoline together with u-calcium
      and u-creatinine, s-total alkaline phosphatases and s-osteocalcin. Blood and
      urine samples were collected five times with 7-day intervals. Urinary parameters
      were expressed as outputs and corrected for creatinine in fasting night urines
      and second void fasting morning urines. The absolute values differed with a
      tendency towards increasing values in the postmenopausal women, but the
      biological variations in relation to menopausal status were not different. The
      biological variability was much higher for the urinary resorptive markers than
      for the formative markers in the blood. The critical difference expressing the
      difference needed between two serial results from the same person to be
      significant at a 5% level was 15% for s-alkaline phosphatases, 18% for s
      osteocalcin, and lowest in the second void fasting morning urines with values of
      28% and 34% for u-pyridinoline/creatinine and u-deoxypyridinoline/creatinine, and
      50% and 112% for u-hydroxyproline/creatinine and u-calcium/creatinine,
      respectively. The index of individuality, denoting the individual variation
      divided by the variation between subjects, was in the range from 0.19 for s
      alkaline phosphatases to 1.23 for u-hydroxyproline/minute in second void fasting
      morning urine making the use of conventional reference intervals difficult. Low
      indices, however, indicate high test performance and offer the possibility of
      stratification of persons within a range. The number of samples required to
      determine the true individual mean value +/- 5% for the single person, ranged
      from 5 for s-total alkaline phosphatases, 6 for s-osteocalcin, 23 for u
      deoxypyridinoline/creatinine in the fasting morning urine to over two hundred for
      u-calcium analytes. It is concluded that, due to high biological variation, a
      single measurement of biochemical markers of bone turnover is of limited utility
      in the individual person. We recommend that routine clinical use of biochemical
      markers should be restricted until further evidence justifies it.

PMID- 9249884
TI  - Acute contractile effects of epidermal growth factor on bladder smooth muscles.
      An in vivo and in vitro study in rats.
AB  - Chronic treatment with epidermal growth factor (EGF) stimulates growth of all
      wall layers of the urinary tract in pigs and rats. Herein, we investigated the
      acute effects of EGF on detrusor smooth muscle activity. For in vivo examination,
      awake rats received EGF (75 micrograms/kg) intravenously and detrusor smooth
      muscle activity was monitored cystometrically. The EGF bolus caused no alteration
      in diuresis but a doubling of the micturition frequency, a 25% increase in
      micturition pressures, and increased irregular baseline contractile activity. For
      in vitro examination detrusor smooth muscle strips were exposed to EGF (1
      microgram/ml). EGF caused contraction and increase in the spontaneous activity.
      In conclusion, EGF increases rat detrusor smooth muscle contractile activity in
      vivo and in vitro. The finding suggests that a direct effect of EGF on bladder
      smooth muscles is part of the genesis to the growth of the detrusor smooth muscle
      observed after chronic EGF treatment.

PMID- 9249883
TI  - Effect of bolus injection versus continuous infusion of furosemide on diuresis
      and neurohormonal activation in patients with severe congestive heart failure.
AB  - Previous studies have demonstrated that continuous infusion of furosemide results
      in increased diuresis and natriuresis compared with bolus administration of the
      drug in patients with severe heart failure. We reasoned that continuous infusion
      of furosemide caused less activation of neurohumoral mechanisms, since other
      studies have shown that bolus administration of furosemide may activate this
      system. We therefore tested the hypothesis that continuous administration of
      furosemide would increase water and sodium excretion due to less activation of
      neurohormones. Eight patients with severe heart failure were studied during
      continuous infusion over 24 h and bolus injections of furosemide twice daily in a
      randomized cross-over study. Bolus administration of furosemide increased
      diuresis and natriuresis significantly in the first 4 h after administration
      compared with continuous administration, but this was later reversed, resulting
      in similar 24 h total output. The neurohormones measured at baseline were all
      markedly elevated. Neither regimens of furosemide caused any further significant
      changes in neurohumoral response except that pro-ANF decreased more during the
      first 8 h after bolus administration compared to continuous infusion. This study
      has demonstrated that bolus administration of furosemide in conventional doses is
      equally effective as continuous intravenous infusion in patients with severe
      heart failure. This may be due to maximal neurohormonal activation in severe
      heart failure (NYHA III-IV) which could not be further activated by bolus
      administration.

PMID- 9249885
TI  - Serum levels of IgG antibodies against Tamm-Horsfall protein and urinary
      excretion of NAG and alpha-1-microglobulin as possible markers for tubular damage
      in patients with a continent ileal reservoir for urinary diversion.
AB  - Serum IgG antibodies against Tamm-Horsfall protein and urinary excretion of NAG
      and alpha-1-microglobulin were measured in 26 patients with a Kock reservoir for
      continent urinary diversion or orthotopic bladder reconstruction in order to
      detect any signs of tubular damage. None of these markers for tubular damage was
      correlated to the postoperative observation time ranging between 2 and 16 years.
      No correlation was found between these markers and signs of renal scarring or
      upper urinary tract dilatation as judged from urographies. A positive correlation
      was demonstrated between NAG excretion and antibodies against Tamm-Horsfall
      protein. The annual reduction in GFR was increased in patients with elevated
      alpha-1-microglobulin excretion but not in patients with elevated titres of
      antibodies against Tamm-Horsfall protein or increased NAG excretion. Patients
      with previous or present reflux nipple problems had elevated excretion of alpha-1
      microglobulin. Regular determinations of alpha-1-microglobulin excretion appear
      to be of value in the follow-up of these patients.

PMID- 9249886
TI  - Extracorporeal shock wave lithotripsy as first line monotherapy of solitary
      calyceal calculi.
AB  - Eighty-four patients with solitary calyceal stones were treated with
      Extracorporeal Shock Wave Lithotripsy (ESWL) as first line monotherapy. The
      indications for treatment were pain in 51 patients (61%), infection in 11
      patients (13%), pain and infection in 18 patients (21%) and others in 4 patients
      (5%). Stone size (largest diameter) was median 9 mm (range 2-25 mm). Follow-up
      consisted of clinical control, isotope renography and a plain film after 1 month;
      hereafter plain films after 3 and 6 months. Auxiliary procedures due to
      steinstrasse were performed in 3 out of 4 patients (1 nephrostomy, 1 nephrostomy
      + ESWL of ureteral fragments, and 1 ureteroscopic manipulation). Retreatment of
      the calyceal stone was performed in 3 patients within 6 months (2 re-ESWL, 1
      lower pole resection). Stone-free (without retreatment or auxiliary procedures)
      were 26/84 (31%) after 1 month, 34/84 (40%) after 3 months and 38/84 (45%) after
      6 months. Free of pain were 43/69 (62%) after 1 month, 50/69 (72%) after 3 months
      and 59/69 (86%) after 6 months. Free of infection were 18/29 (62%) after 1 month,
      19/29 (66%) after 3 months and 21/29 (72%) after 6 months. Complications included
      steinstrasse in 4 patients, sepsis in 3 patients, displacement of JJ-stent in 2
      patients and atrio-ventricular dissociation in 1 patient. To conclude: ESWL as
      first line therapy for solitary calyceal calculi offers good results with regard
      to pain and clearance of infection, but leaves 55% with residual stone material.

PMID- 9249887
TI  - Combined androgen blockade in the treatment of advanced prostate cancer--an
      overview. The Scandinavian Prostatic Cancer Group.
AB  - The value of combined androgen blockade in the treatment of patients with
      advanced prostate cancer is still controversial. In this review by the
      Scandinavian Prostatic Cancer Group, the literature addressing the concept and
      its clinical use is critically reviewed.

PMID- 9249888
TI  - Cellular changes in prostatic carcinoma after treatment with orchidectomy,
      estramustine phosphate and medroxyprogesterone acetate.
AB  - Thirty-three patients with prostatic carcinoma were treated with either
      estramustine phosphate, orchidectomy or high dose medroxyprogesterone acetate.
      Therapy response was evaluated by cytological examination of fine needle
      aspiration biopsies performed before and after 6 weeks treatment. At follow-up,
      11 of 14 patients treated with estramustine phosphate had regressive and/or
      degenerative changes, in 2 patients there were no prostatic carcinoma cells in
      the smears and in one there was a marked reduction of the number of tumour cells.
      In 7 of 10 patients treated with orchidectomy there was a marked reduction of the
      percentage of malignant cells while smears from 3 patients were unchanged. In the
      8 patients treated with high dose medroxyprogesterone acetate the cell patterns
      were unmodified compared with before treatment. We conclude that, in contrast to
      the lack of effect of treatment with medroxyprogesterone acetate, treatment with
      orchidectomy and especially estramustine phosphate caused morphologic cellular
      changes in prostatic carcinoma.

PMID- 9249889
TI  - Trapping of electrolytes during fluid absorption in transurethral resection of
      the prostate.
AB  - Absorption of irrigating fluid into the blood during transurethral resection of
      the prostate is associated with diffusion of sodium ions from the interstitial
      fluid space into the plasma. Some of this sodium is "trapped" and removed from
      the body in connection with bleeding and excretion of urine. The magnitude of
      this sodium loss was calculated over 10-min periods throughout 20 operations
      during which absorption of glycine solution occurred. The amount of trapped
      sodium increased with the amount of blood lost, a 1000-ml bleed correlating with
      a loss of 10 mmol of sodium. Two thirds was trapped with the plasma loss and one
      third with the osmotic diuresis. This mechanism contributes to the absolute loss
      of sodium from the body. The total sodium loss, however, accounts for one third
      of the maximum hyponatraemia and is still dominated by the plasma-derived sodium
      excreted during the glycine-induced osmotic diuresis.

PMID- 9249890
TI  - 13 years' experience of penile fracture.
AB  - Thirty-two cases of penile fracture in 1983-1996 were retrospectively reviewed
      and the patients were recalled for assessment of current status. The time from
      injury to repair ranged from 8 to 31 hours. The tear in the tunica albuginea was
      repaired with absorbable interrupted sutures. All patients were discharged on the
      day after operation. Skin loss required dermal grafting one month postoperatively
      in one patient. Erectile function returned within 2 days and coitus was achieved
      on average 13 days after the repair. Two patients had slight penile curvature
      which did not impede coitus. At long-term follow-up all patients reported
      satisfactory function.

PMID- 9249891
TI  - Urethral needle suspension for male urinary incontinence.
AB  - A rectus fascia sling was used to suspend the bulbous urethra in 12 males with
      total sphincteric incontinence. Incontinence was related to prostatectomy in 3
      patients, to spinal trauma in 3, and to myelodysplasia in 6 patients. In 3
      patients augmentation ileocystoplasty was added to the procedure because of
      reduced bladder capacity and compliance. Needle suspension of the sling
      simplified the procedure and obviated difficult retroprostatic dissection. After
      an average of 13 months 10 out of 11 patients were totally dry, 2 of these are
      voiding spontaneously with little residual while the rest are on intermittent
      catheterization. One patient is still wet because of severe postoperative
      detrusor instability. Urethral erosion occurred in one patient in whom the sling
      was removed. No upper tract deterioration was found until the last follow-up. In
      conclusion, a rectus fascia sling is a readily available alternative to the
      artificial urinary sphincter with comparable success and less reoperation rates.
      Needle suspension of the sling simplified its application in male patients.

PMID- 9249892
TI  - Acupuncture and hypnotic suggestions in the treatment of non-organic male sexual
      dysfunction.
AB  - We have examined the effects of acupuncture and hypnotic suggestions, and
      compared them with placebo in the treatment of male sexual dysfunction with no
      detectable organic cause. The study comprised 15 men (mean age 36.7 +/- 10.43
      years) who received acupuncture treatment, 16 men (mean age 38.4 +/- 10.75 years)
      who underwent hypnosis (mean age 35.3 +/- 11.52 years) and 29 men (mean age 36.2
      +/- 11.38 years) who served as controls. They were interviewed periodically; the
      patients' reports were verified by interviewing their partners. Men who received
      placebo had a 43-47% improvement in sexual function, while the rates of
      improvement in the treated groups were higher, but not significantly so. The
      success rates of acupuncture and hypnotic suggestions were 60% and 75%
      respectively. Although the improvement was not statistically significant,
      treatment with acupuncture could be used as an adjuvant therapy in non-organic
      male sexual dysfunction. The only treatment superior to placebo seemed to be
      hypnosis. A more effective treatment may be obtained by combining these
      therapeutic modalities, but this needs further study.

PMID- 9249893
TI  - Serum magnesium concentration and PTH levels. Is long-term chronic
      hypermagnesemia a risk factor for adynamic bone disease?
AB  - The observation that some subjects with low PTH had elevated plasma magnesium
      (Mg) levels prompted us to analyze in 41 patients on maintenance hemodialysis for
      44 +/- 36 months, their serum Mg concentrations, and the relationship between
      plasma Mg and PTH levels. The mean serum Mg concentration was 2.4 +/- 0.2 mg/dl.
      Twenty-four out of the 41 subjects (58.5%) had hypermagnesemia (serum Mg above
      2.5 mg/dl). Patients were classified into 3 groups according to their PTH level:
      Group A, low PTH (below 120 pg/ml); group B, adequate PTH (120-250 pg/ml); and
      group C, high PTH (above 250 pg/ml). There were no differences among groups
      according to number of subjects, age, sex, time on dialysis, renal disease, serum
      calcium, phosphorus, bicarbonate, vitamin D or aluminum concentrations. Doses of
      calcium carbonate and aluminium hydroxide were also similar in all groups.
      Curiously, although the differences were not statistically significant, the total
      cumulative intake of calcium and aluminium were less in group A than in the other
      groups. Interestingly, patients with low PTH had a significantly higher serum Mg
      concentration than patients with adequate or high PTH (2.8 +/- 0.2 mg/dl vs 2.3
      +/- 0.1 mg/dl and 2.2 +/- 0.1 mg/dl, respectively, p < 0.01). Moreover,
      regression analysis showed a negative linear correlation between serum PTH level
      and plasma Mg concentration (r = -0.6059, p < 0.001). Based on these findings,
      chronic hypermagnesemia could have a suppressive effect on PTH secretion, and it
      could be a risk factor for the development of adynamic bone disease in dialysis
      patients.

PMID- 9249894
TI  - Altered muscle energy metabolism in post-absorptive patients with chronic renal
      failure.
AB  - Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on
      22 non-dyalized chronic renal failure patients (CRF) on a free diet and after
      overnight fasting. Parathormone, glucagon and insulin were determined at the same
      time of biopsies. CRF patients showed significantly low ATP and creatine
      phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found,
      while the pyruvate kinase activity was lower than in the control group. For the
      tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate
      dehydrogenase activities were higher; total NADH cytochrome c reductase activity
      was also high, while cytochrome oxidase activity was slightly lower. Both alanine
      aminotransferase and aspartate aminotransferase activities were considerably high
      in comparison with the control group. In conclusion, our study revealed a
      hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly
      explained the reduced ATP concentration. Excessive protein intake and hormonal
      derangements may play a role in these metabolic changes.

PMID- 9249895
TI  - Analysis of charge distribution of lambda- and kappa-IgA in IgA nephropathy by
      focused antigen capture immunoassay.
AB  - The finding that eluted mesangial IgA and serum IgA from patients with IgA
      nephropathy (IgAN) had a restricted anionic charge contrasting with normal serum
      IgA prompted us to examine the charge of kappa- and lambda-subclasses of IgA.
      Previous studies are not totally satisfactory because either total IgA without
      further dividing into subclass or only kappa- and lambda-IgA1 was examined. A new
      approach is described to study the electrostatic property of total IgA and its
      light chain subclasses. The new focused antigen capture immunoassay (FACIA)
      allows us to separate the immunoglobulins by isoelectric point, then to capture
      by the heavy chain class and finally to visualize according to the light chain
      class. This method works well with whole blood or serum without the need of prior
      purification by affinity chromatography. The serum total IgA and lambda-IgA
      levels in patients with IgAN were significantly higher than that of healthy
      controls. Elevated lambda-IgA levels in patients with IgAN resulted in reduced
      kappa/lambda ratio of total IgA. Similar to our previous findings in IgA1 with O
      linked oligosaccharide side chain, lambda-IgA from patients with IgAN or health
      controls is highly anionic whereas kappa-IgA is relatively cationic. The higher
      anionic/cationic ratio observed in total IgA from patients compared with controls
      was due to the higher concentration of lambda-IgA from the former group. Raised
      anionic lambda-IgA in IgAN may be contributory to the immunopathogenesis through
      its selective mesangial binding.

PMID- 9249896
TI  - Nephrotic syndrome associated with transitional cell carcinoma of urinary
      bladder.
AB  - A 50-year-old male presented with nephrotic syndrome associated with transitional
      cell carcinoma of the bladder. Renal biopsy was suggestive of
      membranoproliferative glomerulonephritis. The proteinuria disappeared 4 weeks
      after the removal of tumour. This is the second reported case of association
      between nephrotic syndrome and transitional cell carcinoma of the bladder.

PMID- 9249897
TI  - Simultaneous Wilms' tumours in monozygotic twins. Case report and review of the
      literature.
AB  - Familial cases of Wilms' tumour indicate that some of these tumours have a
      genetic origin. However, the role of constitutional genetic and shared
      environmental factors in the causation of these tumours, is not well understood.
      We have observed the very rare occurrence of simultaneous Wilms' tumour in
      monozygotic twins; one of them with a bilateral tumour and fatal outcome at 18
      months of age. The other was in good health at the age of 24 years.

PMID- 9249898
TI  - Metachronous renal cell carcinoma metastases to spermatic cord and penis.
AB  - Metastasis of renal cell carcinoma (RCC) to the penis or spermatic cord is rare.
      We present an unusual case of initial metastasis to the cord with delayed
      involvement of the penis. This is the first report of metachronous involvement of
      the genitalia from RCC metastases.

PMID- 9249899
TI  - Retroperitoneoscopic cutaneous ureterostomy.
AB  - A 56-year-old woman presented with bilateral ureteral stenosis and a
      vesicovaginal fistula secondary to advanced cervical carcinoma. Due to the long
      standing obstruction she had a non-functioning right kidney. As a first step the
      function of the contralateral kidney was restored by percutaneous nephrostomy;
      two months later endoscopic cutaneous ureterostomy was performed using a four
      port retroperitoneal approach. The ureter was mobilized, transected and pulled
      out through a 10-mm trocar in the mid-clavicular line. The total operative time
      was 165 min with an estimated intraoperative blood loss of less than 30 ml.
      Convalescence was short.

PMID- 9249900
TI  - Bladder hemangioma as a cause of massive hematuria in a child. A case report and
      literature review.
AB  - A 12-year-old girl with bladder hemangioma presenting with massive hematuria is
      described. The patient was previously operated for removal of cystic hygroma from
      the chest wall. The association of those two pathological entities suggests
      possible common etiology and pathogenesis and the various therapeutic options are
      reviewed.

PMID- 9249901
TI  - Emphysematous cystitis.
AB  - A case of emphysematous cystitis in a diabetic female is described. Its
      presentation is non-specific and the prognosis depends on then degree of
      aggressiveness at presentation. Early diagnosis and aggressive medical and
      surgical management of gas-forming organisms are vital.

PMID- 9249902
TI  - Severe candida cystitis with perforation of the urinary bladder.

PMID- 9249903
TI  - Cowper's gland duct cyst in an adult male. Radiological and clinical aspects.
AB  - A 48-year-old man presenting with perineal pain, weak stream and dysuria was
      found to have a Cowper's gland duct cyst measuring 1.8 x 3.5 cm, which was
      investigated with retrograde and voiding urethrography, cavernosography and
      perineal MRI, which was the single most useful imaging technique. Treatment
      consisted in complete surgical excision, which allowed an anatomical
      reconstruction of the urethra. This condition is typical of the pediatric age
      group, and seldom diagnosed in adults.

PMID- 9249904
TI  - Epididymo-orchitis and Reiter's disease. Two infrequent complications after
      intravesical bacillus Calmette-Guerin therapy.
AB  - Two cases of adverse reactions to intravesical treatment with bacillus Calmette
      Guerin are reported. The first patient presented with a severe suppurating
      epididymo-orchitis three months after his last treatment. The second patient
      developed Reiter's disease with arthritis of one knee and conjunctivitis 1 week
      after the fourth instillation.

PMID- 9249905
TI  - Prognostic factors in prostate cancer.
AB  - The clinical course of prostate cancer (PCa), the most common cancer in Swedish
      men, is highly variable and difficult to predict. Consequently, there is an
      urgent need to distinguish tumours with a high risk of progression from those
      with a low risk. To investigate the prognostic implications of proliferation and
      apoptosis, two important processes in tumor biology, immunoreactivity for
      biomarkers associated with these processes was assessed, quantified in indexes,
      and related to cause-specific survival (CSS). A consecutive series of 186 men
      presenting with voiding symptoms and PCa were treated with transurethral
      resection and deferred endocrine therapy. After 13-21 years follow-up, 43% of
      these men had died of prostate cancer. In a subgroup of men with localised
      disease at the time of diagnosis, 27% succumbed to the disease. Immunoreactivity
      for p53 protein, indicative of a defective p53 function, predicted shorter CSS in
      univariate (52 vs 123 months, p < 0.0001), but not in multivariate analysis. Mean
      index for the apoptosis blocking bcl-2 protein was higher in foci of prostatic
      intraepithelial neoplasia, a putative precursor to PCa, than in manifest cancer
      areas (79 vs 12, p < 0.0001). This indicates that bcl-2 may be involved in early
      tumourigenesis. No prognostic value was found for the bcl-2 index. A high index
      for the proliferation marker Ki-67 predicted shorter CSS in univariate (53 vs 132
      months p < 0.0001) and in multivariate analysis. To test if p53 is predictive for
      clinical radioresistance, as suggested by experimental models, p53
      immunoreactivity was investigated in biopsies obtained before radical
      radiotherapy in an unrelated series of 60 PCa patients. Patients with p53
      reactive tumours had longer CSS, indicating that p53 is not treatment-predictive
      for radiotherapy in Pca. Core biopsies were obtained before and a week after
      castration therapy in patients with advanced PCa. According to the serum prostate
      specific antigen (PSA) level 3 months after therapy, 15 responding tumours and 13
      non-responding tumours were selected. Regressive morphology was seen in 14/15
      responders after castration therapy, compared with 4/13 non-responders. Median
      apoptotic index increased significantly after castration therapy for responders
      (from 2.6 to 3.5, p < 0.05) whereas it was 2.8 before and after therapy in non
      responders. This indicates that subsequent clinical response can be predicted by
      the induction of regressive morphology and an increase in apoptotic index. In
      conclusion, immunoreactivity for Ki-67 appeared to be a putative prognostic
      factor in PCa, whereas the prognostic value of p53 and bcl-2 was dubious. p53
      immunoreactivity did not appear to be predictive of radioresistance in PCa.
      Cellular response in biopsies shortly after castration therapy might be treatment
      predictive.

PMID- 9249906
TI  - Capillary dysfunction in striated muscle ischemia/reperfusion: on the mechanisms
      of capillary "no-reflow".
AB  - The major dysfunction of capillaries after prolonged periods of ischemia is the
      lack of re-establishment of nutritive blood flow upon onset of reperfusion, i.e.,
      capillary no-reflow. Several mechanisms have been proposed to cause capillary no
      reflow, including intravascular hemoconcentration and thrombosis, leukocyte
      plugging, endothelial cell swelling, vasomotor dysfunction, and interstitial
      edema formation. Electron microscopic studies suggest that thrombus formation and
      intravascular clotting are not significant mechanisms. Moreover, intravital
      microscopic studies have demonstrated that plugging of capillaries by leukocytes
      is not a primary cause for the manifestation of no-reflow in postischemic
      striated muscle. In contrast, both in vivo studies and histological examinations
      support the concept that ischemia/reperfusion induces the disruption of the
      endothelial integrity with loss of fluid to endothelial cells and the
      interstitial space. As a consequence, these pathological sequelae are associated
      with intravascular hemoconcentration, endothelial cell swelling and interstitial
      edema formation, which contribute to capillary lumenal narrowing, increase of
      hydraulic resistance, and, thus, impairment of perfusion. Whether the
      postischemic diameter response with dilation of reperfused capillaries and
      lumenal narrowing of no-reflow capillaries involves endothelin/nitric oxide
      triggered capillary pericyte function remains to be determined.

PMID- 9249907
TI  - Methods for studying microvascular barrier function in ischemia-reperfusion
      injury.
AB  - Ischemia-reperfusion (I/R) injury is accompanied by functional disturbances in
      the microcirculation that often translate into significant morbidity and
      mortality. We present an overview of methods to evaluate microvascular barrier
      properties and how these methods can be applied to the study of I/R injury.
      Included is a summary of techniques for measuring 1) fluid and macromolecule flux
      from the vascular compartment into the interstitial space of tissues and 2) the
      permeability parameters of microvascular wall. Several experimental models will
      be surveyed including whole animal, isolated organ, individually perfused
      microvessels and cultured endothelial cells using examples from our own studies
      and work of other investigators relating to I/R-induced endothelial injury. The
      strengths and weaknesses of these different approaches are discussed.

PMID- 9249908
TI  - Ischemia/reperfusion-induced leukocyte-endothelial interactions in postcapillary
      venules.
AB  - The recruitment of leukocytes into postcapillary venules following reperfusion of
      ischemic tissues is a classical inflammatory response that is influenced by a
      balance of adhesive and hemodynamic forces. Initial periods of reperfusion are
      characterized by an elevation in low affinity adhesive interactions between
      leukocytes and endothelial cells, which permit the leukocytes to establish
      intimate contact with the vascular endothelial lining as they roll across it.
      This rolling behavior of leukocytes increases the probability that stronger
      adhesive interactions between leukocyte and endothelial cell will occur, allowing
      the leukocyte to firmly adhere to the endothelium and subsequently to emigrate
      across the venular wall into the interstitial compartment. Several factors appear
      to contribute to the leukocyte-endothelial cell adhesion that is elicited by
      ischemia/reperfusion, including: 1) the magnitude of adhesion molecule expression
      on leukocyte and/or endothelial cell surfaces, 2) reactive oxygen metabolites and
      lipid mediators released from stimulated leukocytes and endothelial cells and 3)
      hemodynamic dispersal forces that act to sweep leukocytes from the microvessel
      wall. Intravital microscopic techniques have allowed investigators to focus on
      inflammatory responses in postcapillary venules, which is the primary site of
      leukocyte adhesion and vascular protein leakage. This technology has also been
      employed to delineate the role of adhesive and hemodynamic factors in promoting
      leukocyte rolling, adhesion, and emigration in postcapillary venules exposed to
      ischemia/reperfusion.

PMID- 9249909
TI  - Therapeutic approaches for clinical ischemia and reperfusion injury.
AB  - Recent clinical applications of strategies derived from microcirculation and
      shock research directed at preventing the sequelae of ischemia and reperfusion
      syndromes are successfully decreasing mortality in a variety of human diseases.
      The most commonly applied principle remains early reperfusion, which has been
      most successfully applied in the treatment of myocardial infarction with balloon
      angioplasty and employed with moderate success in the recent treatment of stroke
      with fibrinolytic agents. This strategy is designed to prevent reperfusion injury
      before it occurs and has limited applicability. A more commonly used principle to
      clinically treat the reperfusion injury component of ischemia and reperfusion
      syndromes is controlled reperfusion, which is now routinely applied in transplant
      and experimentally applied in the treatment of peripheral artery occlusion,
      stroke, and myocardial infarction. Strategies to control the microcirculatory
      environment during ischemia are employed successfully in transplantation and
      cardiopulmonary bypass. These techniques have been recently modified for use in a
      combined fashion with controlled reperfusion in experimental clinical studies in
      heart surgery, limb ischemia, and transplantation. Future strategies that have
      indirect support but have not yet been tested in clinical studies include
      anticytokine therapy and ischemic preconditioning. In conclusion, the successes
      in the treatment of ischemia reperfusion injury in experimental animals have
      slowly been integrated into clinical practice. Marked gains have been made in the
      treatment of myocardial infarction, peripheral artery occlusion, and
      transplantation. On the other hand, in areas such as stroke and hemorrhagic
      shock, we have a long way to go.

PMID- 9249910
TI  - Impaired enterocyte triglyceride synthesis after trauma-hemorrhage and
      resuscitation.
AB  - Although gut lipid absorptive capacity is depressed after trauma and hemorrhagic
      shock, it remains unknown whether this is associated with an impairment in the
      enterocyte triglyceride (TG) synthesis, and if so, whether villus or crypt cells
      participate in the lipid absorption under such conditions. To study this, midline
      laparotomy (i.e., trauma induction) was performed in the rats, and then the
      animals were bled to and maintained at a mean arterial pressure of 40 mmHg until
      40% of shed blood volume was returned in the form of Ringer's lactate. The rats
      were then resuscitated with four times the volume of maximal bleedout with
      Ringer's lactate over 60 min. For lipid loading test, 1 mL of olive oil was given
      intraduodenally as a bolus injection upon the completion of resuscitation. The
      enterocytes along the crypt-villus axis from the proximal small intestine were
      isolated at either 0, 1.5, or 5 h after fat feeding. The intracellular and pre
      chylomicron TG contents as well as the microsomal enzyme activities associated
      with TG synthesis were determined thereafter. The results indicated that
      intracellular and pre-chylomicron TG contents and lipid esterifying enzyme (i.e.,
      acyl-coenzyme A:monoglyceride acyltransferase) activity decreased significantly
      in villus tip cells after trauma-hemorrhage and resuscitation. The intracellular
      TG content and lipid esterifying enzyme activity in crypt cells after trauma and
      hemorrhagic shock were also reduced. However, there was no significant decrease
      in pre-chylomicron TG content in the crypt cells isolated from trauma-hemorrhaged
      rats. It is unlikely that crypt cells participate in lipid transport after trauma
      and hemorrhagic shock. In contrast, the TG synthesis in villus tip cells
      decreased significantly following trauma-hemorrhage and resuscitation, which may
      contribute, at least in part, to the impaired gut lipid absorptive capacity
      observed under such conditions.

PMID- 9249911
TI  - Intestinal alkaline phosphatase: role in the depressed gut lipid transport after
      trauma-hemorrhagic shock.
AB  - Although studies have indicated that the gut lipid absorptive capacity is
      impaired after trauma and hemorrhagic shock, the mechanism responsible for this
      remains unknown. The aim of this study, therefore, was to determine whether
      intestinal alkaline phosphatase (IAP) plays any role in the depressed gut lipid
      absorptive function observed under such conditions. To determine this, 5 cm
      midline laparotomy (i.e., trauma induced) was performed in the rats, and animals
      were then bled to and maintained at a mean arterial pressure of 40 mmHg until 40%
      of shed blood volume was returned in the form of Ringer's lactate. The rats were
      resuscitated with four times the volume of maximal bleedout with Ringer's lactate
      over 60 min. For in vivo lipid loading test, 1 mL olive oil was given
      intraduodenally upon the completion of resuscitation. The enterocytes were
      isolated at either 0, 1.5, or 5 h after fat feeding, and the soluble, membranous
      and pre-chylomicron (pre-CM) IAP activities as well as triglyceride contents were
      determined thereafter. The results indicated that the soluble IAP activity in the
      villus tip cells isolated from trauma-hemorrhaged rats increased significantly at
      0, 1.5, or 5 h after fat feeding. The pre-CMIAP activity, however, decreased
      markedly in villus tip cells at 1.5 or 5 h after lipid administration, which was
      associated with the decreased pre-CM triglyceride contents in villus tip cells
      under such conditions. The altered IAP activity in villus tip cells, therefore,
      appears to play a role in the depressed gut lipid absorption and transport
      following trauma-hemorrhage and resuscitation.

PMID- 9249912
TI  - Establishment and characterization of a line of adipose-derived human
      microvascular endothelial cells (HADMEC-5) transformed by simian virus 40 large T
      antigen expression: application to endotoxin research.
AB  - This paper reports the establishment and initial characterization of an
      immortalized line of human, adipose tissue-derived microvascular endothelial
      cells. Transfection of primary endothelial cell cultures was accomplished by the
      introduction of a plasmid, which contained simian virus 40 large T antigen DNA as
      well as a Rous sarcoma viral promoter region. One emergent colony, termed HADMEC
      5, was isolated and has been passaged 45 times to date. The cells express simian
      virus 40 large T antigen protein, are immunohistochemically positive for factor
      VIII-related antigen, bind Ulex europaeus lectin, and accumulate Dil-labeled
      acetylated low density lipoprotein. The HADMEC-5 line demonstrates a highly
      proliferative growth rate in the absence of supplemental growth factors, when
      compared with primary cultures of nontransformed endothelial cells. HADMEC-5
      growth remains serum dependent, but exhibits a lower serum requirement than
      nontransformed cells. The transformed cells grow well upon a variety of matrix
      compounds and in a variety of growth media. When grown upon Matrigel, the HADMEC
      5 cells form three dimensional tube-like structures. The HADMEC-5 line was also
      tested for its ability to produce eicosanoids in response to bacterial
      lipopolysaccharide. The transformed cells, tested at passages 7 and 45, displayed
      a dose-dependent production of prostaglandin E2 in response to lipopolysaccharide
      in a manner similar to that seen in primary cell cultures. Threshold sensitivity
      to lipopolysaccharide was 10 pg/mL of media. The HADMEC-5 cell line represents a
      unique model in which to investigate lipopolysaccharide interactions with
      microvessel-derived endothelial cells and is of potential value in the study of
      other aspects of endothelial cell physiology.

PMID- 9249913
TI  - Age does not affect thermal and cardiorespiratory responses to microwave heating
      in calorically restricted rats.
AB  - This study sought to determine whether age influences the thermal distribution
      and cardiorespiratory responses to 35 GHz microwave (MW) heating. Male Sprague
      Dawley rats (n = 8/group) 3 to 4 mo old (young), 15 to 16 mo old (middle-aged),
      and 24 to 25 mo old (old) were used. All animals were restricted to 63% of ad
      libitum feed. Rats were anesthetized (ketamine) and a catheter was placed into a
      carotid artery for measurement of mean arterial blood pressure (MAP).
      Anesthetized rats were then exposed to MWs until death, while measuring MAP,
      heart rate and temperatures at five sites (colonic, left and right tympanic,
      subcutaneous, and tail). Before MW exposure, there were no significant (p < .05)
      differences among age groups in measured parameters. MW produced increases in
      temperature at each of the measured sites; temperatures at death did not differ
      between groups. Heart rate increased throughout MW exposure, in a statistically
      identical manner in all age groups. MAP was initially well maintained and then,
      in the latter phases of heating, precipitously declined until death, with no
      discernible age-related difference. Respiration rate was not altered by MW
      exposure in any group. Finally, there were no group differences in the MW
      exposure time required to induce death. Thus, age does not alter thermal and
      cardiorespiratory responses to 35 GHz MW heating in food-restricted rats.

PMID- 9249914
TI  - Morphometric analysis of oleic acid-induced permeability pulmonary edema:
      correlation with gravimetric lung water.
AB  - The technique used most commonly to quantitate pulmonary edema in in vivo animal
      models is postmortem gravimetric analysis (wet:dry) ratio. To determine whether
      lung water can be quantitated morphometrically, as accurately as by the commonly
      used gravimetric analysis, perivascular edema (cuff) area to vessel area ratio
      was correlated to wet:dry ratio. Anesthetized pigs were given either oleic acid
      (20 mg/kg/h, intravenously) or physiologic saline. At 4 h, lungs were excised and
      cuff:vessel and wet:dry ratio analysis was performed. The intermediate lobe was
      clamped across its main stem bronchus to maintain peak inspiratory inflation,
      excised, frozen in liquid nitrogen, and stored at -70 degrees C until cryostat
      sectioning and quantification of perivascular interstitial edema (cuff) area.
      Gravimetric analysis (wet:dry ratio) was performed on the remaining lung. Mean
      cuff:vessel and wet:dry analyzes showed that lung water increased significantly
      (p < .01) in the oleic-acid treated group (4.9 +/- .22 and 6.78 +/- .47,
      respectively), compared with the saline group (.03 +/- .02 and 2.55 +/- .27,
      respectively). The correlation coefficient between mean cuff:vessel and wet:dry
      ratios was .86 (p = .0016). This study demonstrates that cuff:vessel ratio
      analysis can be used to identify the distribution of edema fluid versus vessel
      diameter, and seems to be as effective a technique as gravimetric analysis to
      quantitate lung water changes in acute lung injury models. Moreover cuff:vessel
      ratio analysis can differentiate modest changes in pulmonary edema by direct
      quantitation, an important end-point not provided by wet:dry analysis. Therefore,
      it may be a more sensitive technique when investigating therapeutic interventions
      in in vivo models of acute lung injury.

PMID- 9249915
TI  - Protein kinase a activity is increased in rat heart during late hypodynamic phase
      of sepsis.
AB  - Changes in the activities of protein kinase A (PKA, or cAMP-dependent protein
      kinase) in rat heart during different cardiodynamic phases of sepsis were
      investigated. Sepsis was induced by cecal ligation and puncture. Experiments were
      divided into three groups: control, early sepsis, and late sepsis. Early and late
      sepsis refers to those animals killed at 9 and 18 h, respectively, after cecal
      ligation and puncture. Cardiac PKA was extracted and partially purified by acid
      precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography.
      PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks
      of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic
      strength), were collected and their activities were determined based on the rate
      of incorporation of [gamma-32P]ATP into histone. Results obtained show that
      during early sepsis, both type I and type II PKA activities were unaffected.
      During late sepsis, type I PKA activities were stimulated by 66.7-97.7%, while
      type II PKA activities remained constant. Kinetic analysis of the data on type I
      PKA during late sepsis reveals that the Vmax values for ATP, cAMP, and histone
      were increased by 84.7, 66.7, and 97.7%, respectively; while the Km values for
      ATP, cAMP, and histone were unaltered. These data indicate that type I PKA is
      activated in rat heart during late hypodynamic phase of sepsis. Since kinase
      mediated phosphorylation plays an important role in regulating myocardial
      function and metabolism, an activation of type I PKA during late sepsis may
      contribute to the development of altered myocardial function during hypodynamic
      phase of sepsis.

PMID- 9249916
TI  - Cytokine production precedes the expansion of CD14+CD16+ monocytes in human
      sepsis: a case report of a patient with self-induced septicemia.
AB  - We describe a patient with self-induced disease who presented with repeated
      urinary tract infection and sepsis due to intravesical and intravenous injection
      of feces. Sepsis occurred repeatedly such that the patient exhibited 10 bouts of
      fever > 40 degrees C in a single month. This bacterial challenge led to massive
      activation of the monocyte system with high levels of TNF-alpha, IL-6, and
      monocyte colony-stimulating factor (M-CSF). This cytokine response was followed
      by strong expansion of the novel CD14+CD16+ monocyte subset. These results
      suggest that cytokines induce the development of CD14+CD16+ cells in human
      septicemia and that CD14+CD16+ cells may serve as indicator for previous bouts of
      excessive inflammation.

PMID- 9249917
TI  - Long-term survival of breast cancer in Norway by age and clinical stage.
AB  - In this paper 25-year survival for 8802 Norwegian women with breast cancer
      diagnosed during the period 1965 to 1974 is studied. It is suggested that some of
      the contradictory reports in the literature of the prognostic effect of age and
      clinical stage on long-term survival may be caused by interactions and time
      varying effects of covariates. When using a linear non-parametric regression
      model that allows the covariates to vary over time, age and clinical stage are
      found to be significant long-term prognostic factors. A significantly higher
      excess mortality for women less than 35 years at diagnosis disappeared after 8
      years, while for those above 55 years an important effect of age on the long-term
      survival, especially for those with regional cancer, was seen. The effect of
      clinical stage on survival varies strongly over time, and was significant between
      15 and 20 years.

PMID- 9249918
TI  - Predicting in-hospital mortality of patients with AIDS-related Pneumocystis
      carinii pneumonia: an example of hierarchically optimal classification tree
      analysis.
AB  - A non-linear statistical classification methodology known as hierarchically
      optimal classification tree analysis (CTA) offers promise of outperforming linear
      alternatives. We present the first example of CTA in medicine, for an application
      that uses four attributes (age, body mass index, alveolar-arterial oxygen
      gradient, prior history of AIDS) to predict in-hospital mortality for a sample of
      1339 patients with AIDS-related Pneumocystis carinii pneumonia. We also
      illustrate use of a hold-out (cross-generalizability) sample that suggests a
      three-attribute model (alveolar-arterial oxygen gradient, total lymphocyte count,
      private insurance). Both CTA models achieved approximately 25 per cent of the
      total possible theoretical improvement beyond chance in classification accuracy
      (for comparative purposes, logistic regression and regression-tree models
      obtained in prior research returned less than 10 per cent). We illustrate how one
      can use CTA models to construct staging systems for assessing severity of
      illness, and for identifying important directions for future research. In the
      context of the example, we discuss additional advantages of CTA versus linear
      alternatives that include treatment of missing data, control of experimentwise
      type I error, richness of the substantive findings, and ease of use.

PMID- 9249919
TI  - Non-iterative robust estimators of variance components in within-subject designs.
AB  - Classic estimators of variance components break down in the presence of outliers
      and perform less efficiently under non-normality. In this article I present
      simple non-iterative estimators of variance components that are resistant to
      outliers and robust to systematic departures from normality, such as heavy
      tailedness of the distribution of responses. The proposed estimators are based on
      a robust extension of Hocking's AVE approach and are thus called RAVE estimators.
      I present results from a Monte Carlo comparison of RAVE versus classic estimation
      methods including maximum likelihood (ML), restricted maximum likelihood (REML)
      and minimum variance quadratic unbiased estimation (MIVQUE). Under simulated
      deviations from normality, RAVE estimators are associated with smaller mean
      squared errors than all the comparators, and in the normal case they exhibit a
      minimal loss in relative efficiency. A numerical example illustrates the proposed
      methodology.

PMID- 9249920
TI  - Detection rates and false positive rates for Down's syndrome screening: how
      precisely can they be estimated and what factors influence their value?
AB  - Down's syndrome screening is currently carried out using a combination of
      biochemical markers measured in maternal serum samples; these include MSAFP,
      Total hCG, uE3 and Free beta-hCG. Recently a number of papers have compared the
      effectiveness of different combinations of these markers. Some recommend MSAFP,
      Total hCG and uE3 (triple test) while others advocate MSAFP and Free beta-hCG
      (double test). The cases put forward to support these tests rely on estimated
      detection and false positive rates for the proposed test. A recent paper by
      Wright used simulation techniques to estimate the effects of sampling error on
      such error rates. In prospective studies there are two methods commonly used for
      estimating these rates. We obtain formulae for the standard deviations of these
      estimates and show that one of them always gives a smaller standard error than
      the other. We also show that in such studies the accuracy of estimating detection
      rates and false positive rates depends not only upon the method of calculation
      but also on the age distribution of pregnant women and the parameters used to
      calculate patient specific risk. We show that these effects can result in
      estimation errors of such magnitude that many observed differences in detection
      rates could be of questionable significance, a conclusion also reached by Wright.

PMID- 9249921
TI  - Statistical analysis of intraclass correlations from multiple samples with
      applications to arterial blood pressure data.
AB  - We consider inference procedures on intraclass correlations for unbalanced data
      from several multivariate normal populations. We derive several tests, including
      ones based on Fisher's variance stabilizing transformation and Neyman's score
      functions, to test the homogeneity of intraclass correlations. We illustrate the
      methodology with an example that uses arterial blood pressure data collected by
      Miall and Oldham and we compare the procedures in terms of their empirical levels
      and powers with a Monte Carlo simulation study. We recommend the use of Neyman's
      C(alpha) test and a test based on the ANOVA estimators of the intraclass
      correlations as they hold their significance levels and give consistently higher
      powers.

PMID- 9249922
TI  - Estimating the proportion of treatment effect explained by a surrogate marker.
AB  - In this paper, we measure the extent to which a biological marker is a surrogate
      endpoint for a clinical event by the proportional reduction in the regression
      coefficient for the treatment indicator due to the inclusion of the marker in the
      Cox regression model. We estimate this proportion by applying the partial
      likelihood function to two Cox models postulated on the same failure time
      variable. We show that the resultant estimator is asymptotically normal with a
      simple variance estimator. One can construct confidence intervals for the
      proportion by using the direct normal approximation to the point estimator or by
      using Fieller's theorem. Extensive simulation studies demonstrate that the
      proposed methods are appropriate for practical use. We provide applications to
      HIV/AIDS clinical trials.

PMID- 9249923
TI  - Sample size determination for diagnostic accuracy studies involving binormal ROC
      curve indices.
AB  - Receiver operating characteristic (ROC) curves and their associated indices are
      valuable tools for the assessment of the accuracy of diagnostic tests. The area
      under the ROC curve is a popular summary measure of the accuracy of a test. The
      full area under the ROC curve, however, has been criticized because it gives
      equal weight to all false positive error rates. Alternative indices include the
      area under the ROC curve in a particular range of false positive rates ('partial'
      area) and the sensitivity of the test for a single fixed false positive rate
      (FPR). We present a unified approach for computing sample size for binormal ROC
      curves and their indices. Our method uses Taylor series expansions to derive
      approximate large-sample estimates of the variance and covariance of binormal ROC
      curve parameters. Several examples from diagnostic radiology illustrate the
      proposed method.

PMID- 9249924
TI  - Never-ending tales of the mode of the teratogenic action of thalidomide.

PMID- 9249925
TI  - Interaction of [glutarimide-2-14C]-thalidomide with rat embryonic DNA in vivo.
AB  - We have investigated the possibility of [phthalimide carbonyl-14C]thalidomide and
      [glutarimide-2-14C]thalidomide interaction with DNA. In each experiment, groups
      of pregnant Wistar rats were treated with a labeled compound on day 12 of
      gestation. The embryos were harvested 24 h later, and dimethlformamide-treated
      control groups and groups treated with the same labeled compound and with the
      same radioactive doses were pooled respectively and analyzed. The DNA from each
      group was purified and monitored for 14C radioactivity. Low but statistically
      significant radioactivity was detected in only the DNA samples prepared from the
      [glutarimide-2-14C]thalidomide-treated embryos. This result demonstrates the
      binding of the glutarimide moiety, or its reactive intermediates, with rat
      embryonic DNA in vivo.

PMID- 9249926
TI  - Analysis of cytogenetic effects and DNA adduct formation induced by safrole in
      Chinese hamster lung cells.
AB  - Safrole (1-allyl-3,4-methylenedioxybenzene) was tested for its ability to induce
      sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) and to form
      DNA adducts in Chinese hamster lung (CHL) cells, in order to investigate the
      relationship between cytogenetic effects and DNA adduct formation under the same
      treatment conditions. The cells were treated with 0.025-0.2 mg/ml safrole in the
      presence or absence of rat liver postmitochondrial supernatant fraction (S9).
      Safrole induced significant SCEs and CAs dose-dependently in the presence of S9.
      SCEs ranged in number from 15.6 to 21.1 SCEs/cell and CAs were observed in 4-37%
      of cells. Using the 32P-postlabeling assay, two major and two minor safrole-DNA
      adducts were detected in DNA digests obtained from CHL cells in the presence of
      S9. The levels of total DNA adducts ranged from 1.3 to 22.8 adducts/10(7)
      nucleotides. The two major adducts were shown to be guanine derivatives since
      these adducts comigrated on polyethylenimine plates with the adducts produced by
      the reaction of safrole with 2'-deoxyguanosine 3'-monophosphate. A correlation
      was seen between DNA adducts and SCEs or CAs. Neither induction of SCEs and CAs
      nor formation of DNA adducts was observed in the absence of S9. These findings
      suggest that SCEs and CAs induced by safrole result from covalent DNA
      modification metabolically activated by S9 in cultured cells.

PMID- 9249927
TI  - 1,2-Dimethylhydrazine carcinogenesis in C3HA and CBA female mice prenatally
      treated with diethylstilbestrol.
AB  - C3HA and CBA female mice received a single intraperitoneal (i.p.) injection of
      0.1 or 0.3 mg/kg body weight (b.w.) of diethylstilbestrol (DES) at day 17 of
      pregnancy. The descendants, starting from the age of 2-3 months, were receiving
      weekly subcutaneous (s.c.) injections of 1,2-dimethylhydrazine (DMH) (8 mg/kg
      b.w.), total 20 injections. The survival of C3HA mice treated with DMH together
      with prenatal DES was considerably better than in mice treated with DMH alone,
      this being due to the strong inhibiting effect of DES on the induction by DMH of
      the hemorrhagic ovarian lesions (78.4% in DMH alone vs. 53.3 and 43.7% in groups
      with DES plus DMH), which frequently were the cause of animal death. Prenatal DES
      also inhibited the induction by DMH of clitoral gland tumors: 51.4% in the group
      with DMH alone vs. 26.6 and 28.1% in two groups of DES plus DMH, respectively.
      DES treatment, at the above doses, did not influence significantly the DMH
      carcinogenesis in CBA mice. Prenatal DES given to CBA mice at the dose of 1 mg/kg
      b.w. significantly increased the incidence of DMH-induced uterine sarcomas (42.8%
      vs. 73.3% in the group with DMH alone and the group receiving DMH together with
      prenatal DES, respectively) and accelerated their growth. The effects of prenatal
      DES on DMH-induced carcinogenesis correlated with the degree of
      hyperestrogenization produced in both strains of mice by DES.

PMID- 9249928
TI  - Effect of various genotoxins and reproductive toxins in human lymphocytes and
      sperm in the Comet assay.
AB  - There have been conflicting reports as to whether the mean sperm count in some
      men has diminished over the last 50 years. The downward trend has been suggested
      to coincide with an increase in exposure to estrogen-like compounds. These
      estrogenic substances are ubiquitous in the environment. We have examined the
      effect of such substances (diethylstilbestrol, beta-estradiol, daidzein,
      genestein, and nonylphenyl) in the single cell gel electrophoresis assay (Comet
      assay) in human sperm and compared responses with those from human peripheral
      lymphocytes in the same donor and in peripheral lymphocytes from a female donor.
      In addition, effects from the estrogens have been compared to those from known
      reprotoxins and genotoxins. These include lead sulfate, nitrate and acetate,
      dibromochloropropane, ethylene glycol monoethyl ether, 1,2-epoxybutene, and
      1,2,3,4-diepoxybutane. All compounds produced positive responses, but ethylene
      glycol monoethyl ether only produced positive responses in sperm cells in the
      male and not in peripheral lymphocytes, and similarly the phytoestrogens
      (genistein, daidzein) were less responsive in the peripheral lymphocytes in the
      male than in the sperm. This may be due to greater sensitivity of sperm cells
      because of their lack of repair. However, since damage was generally seen over a
      similar dose range, a one-to-one ratio of somatic and germ cell damage was
      observed and has implications for man for risk assessment purposes.

PMID- 9249929
TI  - Physiological parameter values for physiologically based pharmacokinetic models.

PMID- 9249930
TI  - Red blood cell glycerol lysis and hematologic effects in occupational benzene
      exposure.
AB  - Forty-nine female workers in the shoemaking industry, exposed to a solvent
      mixture containing benzene and twenty-seven non-exposed controls, were
      investigated. Concentrations of benzene and toluene in the working atmosphere, as
      well as benzene and toluene in blood and phenols in pre- and post-shift urine as
      parameters of biological monitoring, were determined. In order to assess
      hematotoxic risk, a complete blood cell count with differential, hemoglobin,
      hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean
      corpuscular hemoglobin concentration, reticulocytes, serum iron, alkaline
      phosphatase in neutrophils and red blood cell glycerol lysis time were determined
      in all subjects. Benzene concentrations in the workplace atmosphere at the
      shoemaking factory ranged from 1.9 to 14.8 ppm (median = 5.9). Significant
      difference in benzene in blood (p = 0.005) and phenol in post-shift urine (p =
      0.003) between exposed workers and controls confirmed exposure to benzene.
      Hemoglobin level (p = 0.02) and mean corpuscular hemoglobin concentration (p =
      0.0002) in the shoe workers were lower, and band neutrophils (p = 0.005) and mean
      corpuscular volume (p = 0.03) higher, than in controls. Red blood cell glycerol
      lysis time was significantly higher (p = 0.000001) in shoe workers (X +/- SD =
      41.6 +/- 8.9) than in controls (X +/- SD = 31.1 +/- 6.5) and showed a significant
      correlation with exposure biomarkers. The results confirm that benzene exposure
      below 15 ppm may produce qualitative abnormalities, particularly
      macroerythrocytosis and increased red cell glycerol resistance, in the absence of
      an overt quantitative decrease in circulating blood cells. Increased resistance
      to the hemolytic action of glycerol is a potentially useful biological monitoring
      procedure in medical surveillance of benzene exposed workers. The results of this
      study suggest that potential threshold concentration for hematologic effects of
      benzene is lower than 15 ppm.

PMID- 9249931
TI  - Breast-feeding exposure of infants to cadmium, lead, and mercury: a public health
      viewpoint.
AB  - The purpose of this report is to provide an overview of the public health
      implications of exposure via breast milk to cadmium, lead, and mercury for
      nursing infants and to provide health-based guidance. Daily intakes were
      calculated and compared with guidance values used for public health assessments
      at hazardous waste sites. Cadmium, lead, and mercury under normal conditions are
      found in breast milk at concentration ranges of < 1 microgram/L, 2-5
      micrograms/L, and 1.4-1.7 micrograms/L, respectively. Women exposed
      environmentally or occupationally can have higher levels in their breast milk.
      Concentrations of about 5 micrograms/L (cadmium), 20 micrograms/L (lead), and 3.5
      micrograms/L (mercury) appear to be adequate screening levels. Many factors
      affect both the distribution of cadmium, lead, and mercury in breast milk and the
      health consequences to an infant. It is not clear what additional impact low
      level exposure via breast milk may have on an infant born with a body burden to
      one of these metals. There is sufficient evidence to make the case that
      contaminated breast milk is a source of potential risk to infants in certain
      populations. Prevention strategies that include behavior modification and proper
      nutrition should be communicated to women at risk. Identification and elimination
      of exposure pathways and a critical analysis of the benefits of breast feeding
      versus heavy metal exposure are needed on a site-specific or individual basis.
      Research is required to better understand the impact of low-level exposure to
      heavy metals via breast milk. Breastfeeding should be encouraged under most
      circumstances.

PMID- 9249932
TI  - Prevalence of pathogenic Acanthamoeba (Protozoa:Amoebidae) in the atmosphere of
      the city of San Luis Potosi, Mexico.
AB  - Several species of pathogenic Acanthamoeba cause infections to humans, but
      amoebic keratitis is more frequently found than any other due to the increasing
      number of contact lens wearers in the world. Cysts and trophozoites of these
      amebas are airborne and may pollute water from the air. We investigated the
      proportion of pathogenic Acanthamoeba from the atmosphere of the city of San Luis
      Potosi. Samples were taken by the impinger method, every month during one year.
      We isolated 23 strains of Acanthamoeba, 61% of them were non-pathogenic, 31% were
      non-pathogenic with invasive capacity and 8% were pathogenic to mice. Almost 40%
      of these strains represent danger of infections to humans. The isolations were
      more abundant during the dry season in the south (urban) and west (suburban)
      stations, which means that the sanitary conditions around stands may enhance the
      proportion of pathogenic strains in the surroundings.

PMID- 9249933
TI  - A hazard ranking of organic contaminants in refinery effluents.
AB  - An environmental hazard ranking model (benchmark ranking model) has been
      developed and used for the ranking of organic compounds likely to be found in
      petroleum refinery effluents. The hazard function is essentially a multiplication
      of variables for toxicity (as LC50), octanol-water ratio (Kow), soil adsorption
      (Koc), solubility (S), and half-life (T1/2). The final score is obtained by
      taking the logarithm of the hazard and normalizing the values from 1-10. It is a
      benchmark ranking (BR) approach in the sense that the hazard for chemicals with
      essentially unknown environmental behaviors may be compared with the hazard for
      chemicals with well-known behaviors. In general, debates on water pollution have
      focused on non-polar (hydrophobic) compounds whereas polar (water soluble)
      compounds have attracted much less attention and regulation. This study focuses
      on a number of the polar compounds (methyl-tertiary-butyl-ether [MTBE],
      morpholine, metanolamine and others) since there are indications that some of
      these may cause environmental damage. While non-polar compounds receive the
      highest score in the study, the combination of frequently large volumes, low
      biodegradability, low treatability, and analytical detection problems suggest
      caution when neglecting polar compounds in waste minimization pursuits and in the
      assessment of environmental hazard and damage.

PMID- 9249934
TI  - Tacrolimus-based immunosuppression after liver transplantation: a randomised
      study comparing dual versus triple low-dose oral regimens.
AB  - To evaluate the efficacy and safety of oral tacrolimus-based immunosuppressive
      induction therapy, 130 primary orthotopic liver transplant (OLT) recipients were
      randomised to treatment in an open, parallel-group, European multicentre trial.
      Following OLT, patients were immediately administered either tacrolimus (0.10
      mg/kg) and prednisolone (dual therapy group) or tacrolimus (0.06 mg/kg) in
      conjunction with prednisolone and azathioprine (triple therapy group) both
      orally. Patient survival at 1 year was 79.4% for the dual therapy group and 88.7%
      for the triple therapy group (P = 0.194); 1-year graft survival rates were 76.5%
      in the dual therapy group and 80.6% in the group receiving triple therapy (P =
      0.615). The frequencies of rejection (dual therapy 42.6%, triple therapy 50.0%; P
      = 0.482), infection, and other complications (renal, neurological and glucose
      metabolic disorders) were similar in both groups. Tacrolimus whole blood trough
      concentrations were detectable on days 1 and 2, respectively, in the dual and
      triple therapy treatment groups whilst median tacrolimus blood concentrations in
      the triple therapy group reached levels similar to those in the dual therapy
      group on postoperative day 11 following a steady increase in dose. After 1 year,
      54.4% of the patients randomised to dual therapy were receiving tacrolimus
      monotherapy and only 56.4% of the patients randomised to triple therapy continued
      to receive azathioprine. In conclusion, oral tacrolimus-based immunosuppression
      is both potent and safe when administered as induction therapy after OLT.
      Treatment may commence at either 0.06 or 0.10 mg/ kg per day, but doses may need
      to be increased to the latter value within the first 10 days to maintain
      effective immunosuppression.

PMID- 9249935
TI  - Suppressed alloreactivity and mixed chimerism in rats with accepted cardiac
      allografts by intrathymic injection of donor bone marrow cells.
AB  - Intrathymic injection of donor bone marrow cells (ITBMCs) at the time of
      transplantation and treatment with antilymphocyte serum (ALS) permitted the
      indefinite survival of Brown Norway (BN, RT1n) rat heart grafts in 6 out of 8
      Lewis (LEW, RT1l) rat recipients, LEW recipients with long-surviving BN heart
      grafts (LSGs) also accepted additional BN heart grafts without further
      immunosuppression, though they rejected Piebald Virol Glaxo (PVG, RT1c) rat heart
      grafts in the usual fashion. In the in vitro study, the proliferative response of
      the lymphocytes from LEW recipients with LSGs remained suppressed when they were
      stimulated by BN spleen cells, but not when stimulated by PVG cells. Bone marrow
      cells (BMCs) from LEW rats with LSGs showed strong, nonspecific, suppressive
      effects on the proliferative response in the mixed lymphocyte culture reaction,
      suggesting that one of the possible explanations for tolerance might be the
      involvement of a suppressor mechanism.

PMID- 9249936
TI  - Prognostic factors of long-term allograft survival in 632 CyA-treated recipients
      of a primary renal transplant.
AB  - A total of 632 cyclosporin (CyA)-treated primary renal allograft recipients with
      a functioning graft at 6 months were retrospectively evaluated for risk factors
      correlated with long-term allograft function. Mean follow-up after the 6th month
      was 68.4 +/- 40.6 months. One hundred twenty-one of these patients (19%) were
      lost: 29 died (23/29 with a functioning graft), 77 of the remaining 92 (83%) lost
      their graft because of chronic allograft dysfunction, 9 due to recurrence of
      glomerulonephritis, 5 due to renal artery thrombosis, and 1 due to chronic CyA
      toxicity. At univariate analysis, factors correlated with a better renal (R) and
      pure renal (PR) allograft survival were: dialysis duration of less than 5 years,
      fewer than 2 rejections within the 6th post-Tx month, immediate graft function
      recovery, plasma creatinine below 1.5 mg/dl at the 6th month, age at Tx above 15
      years, and receiving a living donor graft. Cox's regression analysis was also
      performed to obtain relative risks for the same parameters. Long-term dialysis
      patients had more frequent late recoveries (P = 0.002) and reductions in therapy
      (P = 0.01) in order to reduce the side effects of steroids. In young patients
      receiving an initial oral CyA dose of 17 mg/kg per day, steroids were stopped at
      the 6th month in order to achieve catch-up growth: only one such patient lost his
      graft. In contrast, 72% of the young patients who lost their grafts received an
      initial oral CyA dosage of 13 mg/ kg per day. Thus, young patients did worse not
      because of steroid withdrawal, but because of inadequate initial CyA dosage.
      These results suggest that although we cannot exclude alloantigen-independent
      mechanisms as factors that stimulate progression of chronic allograft
      dysfunction, it would appear that the initial lesions are induced by events
      mostly mediated by immunological mechanisms.

PMID- 9249937
TI  - Indirect T-cell allorecognition and the mechanisms of immunosuppression by
      allogeneic blood transfusions.
AB  - LEW rats given twice weekly intravenous transfusions of DA blood for 10 weeks
      showed a strong antibody response to intact DA class I antigens at day 7 that
      declined to undetectable levels by week 6. The response remained undetectable for
      the remainder of the course, in spite of the repeated transfusions of DA blood.
      At week 6 during the blood transfusion course, the LEW rats were immunised with a
      DA class I peptide known to be recognised by LEW CD4+T cells in a LEW APC
      dependent manner. This resulted in the prompt reappearance of a strong antibody
      response to intact DA class I antigen. However, in vitro T-cell proliferation
      responses to peptide 1 appeared to be partially suppressed by the blood
      transfusions. Immunisation of LEW rats with this peptide 4 weeks before
      commencement of the course of DA blood transfusions prevented the decline in
      antibody levels normally seen during the blood transfusion course. These data
      indicate that the multiple blood transfusions are able to induce, in non
      sensitised recipients, a reversible suppression of the indirect T-helper response
      specific for allogeneic peptides in the blood transfusion. Although our protocol
      of twice weekly transfusions does not correspond to the clinical pattern of blood
      transfusions, our results raise the possibility that antigenic cross-reactivity
      at the level of small polymorphic MHC peptides between blood and organ donors
      might represent the immunological basis for the beneficial effects of random
      blood transfusions.

PMID- 9249938
TI  - Is obesity still a risk factor in renal transplantation?
AB  - At our center, since 1982, a body mass index (BMI) of less than 30 has been a
      prerequisite for placing a patient on the waiting list for renal transplantation.
      This decision was made because obese transplant recipients seemed to have a less
      than favorable post-transplant outcome. The aim of this study was to evaluate
      whether this requirement is still justified. Forty-six patients with a BMI above
      30 underwent primary cadaveric renal transplantation between 1972 and 1993. For
      each of these obese patients, five consecutive non-obese (BMI 20-25) control
      patients were selected. Patient and graft survival, causes of graft loss, and
      acute rejection rate were evaluated for the two patient groups before and after
      the year 1982. Within the first 30 post-transplant days, one patient (2%) and 11
      grafts (24%) were lost in the group of obese patients whereas seven patients (3%)
      and 36 grafts (16%) were lost in the control group. Among the obese patients,
      renal circulatory complications were a major cause of graft loss. In the period
      1973-1981, the 1-year patient survival rate was 65% among obese patients versus
      75% among controls from 1982 to 1993, this was 90% versus 93%. From 1973 to 1981,
      the 1-year graft survival rate was 25% among obese patients versus 53% among
      controls (P < 0.05); from 1982 to 1993, it was 68% versus 84% (P = NS).
      Multivariate analysis showed that the immunosuppressive regimen, age of the
      patient, BMI, and cold ischemia time of the graft had a significant influence on
      graft survival. The acute rejection rate within the first 30 days was 28% among
      obese patients and 35% among controls (P = NS). We conclude that a BMI below or
      equal to 30 is still justified as a prerequisite for placement on the waiting
      list for renal transplantation, for despite an overall improvement, the outcome
      of renal transplantation in obese patients remains worse than that in non-obese
      patients.

PMID- 9249939
TI  - Liver transplantation for alcoholic cirrhosis with anti-HCV antibodies.
AB  - The results of orthotopic liver transplantation (OLT) in patients with alcoholic
      liver cirrhosis (ALC) are currently similar to those obtained in patients with
      other indications. However, the frequent association of ALC with hepatitis C
      virus (HCV) infection may impair these results. We retrospectively studied the
      consequences of HCV infection on survival and graft function in 59 patients with
      ALC undergoing OLT. Patients were classified into two groups depending on their
      HCV serology before transplantation: group 1 comprised 24 anti-HCV-positive
      patients, and group 2, 35 anti-HCV-negative patients. Patient and graft survival
      were similar in both groups. Liver function tests 1 and 4 years after OLT showed
      AST and ALT values that were significantly higher in group 1 patients and post
      transplant histologically proven chronic hepatitis was found in 45% and 61% of
      these patients at 1 and 4 years, respectively. We conclude that pretransplant HCV
      infection in patients with ALC does not affect survival after OLT. However, one
      must bear in mind the high incidence of post-transplant chronic hepatitis
      secondary to recurrence of HCV infection and be cautious when drawing this
      conclusion.

PMID- 9249940
TI  - The induction of operational tolerance is not prevented by simultaneous
      administration of cyclosporin A1.
AB  - In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and
      cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse
      cardiac allograft model was used. Anti-CD4 mAb administered perioperatively
      induces long-term survival. The addition of a short course of CyA given
      subcutaneously in a regimen of either a high-dose treatment or a standard dose
      treatment to the anti-CD4 mAb treatment protocol did not have a detrimental
      effect on graft survival. Despite having no significant effect on graft survival,
      the addition of CyA to the treatment protocol did result in a significant
      decrease in the level of IL-2 present in the hearts 7 days after transplantation.
      The decrease in IL-2 production was directly related to the presence of CyA in
      vivo. When CyA treatment was continued throughout the period during which
      unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50% of the
      grafted hearts were rejected once the CyA was discontinued. In conclusion, the
      combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on
      graft survival in this model when the two agents were used concurrently at the
      time of transplantation.

PMID- 9249941
TI  - The isolated perfused porcine liver: assessment of viability during and after six
      hours of perfusion.
AB  - Isolated liver perfusion was developed for the study of liver physiology and
      preservation. The recent development of new perfusion devices and appropriate
      liver preservation solutions prompted us to reconsider liver perfusion for the
      specific purpose of evaluating viability in terms of biochemical changes, paying
      special attention to modifications in the histological ultrastructure. Twenty-two
      isolated pig livers were perfused with autologous blood. Arterio-portal
      perfusions were carried out using an extracorporeal perfusion circuit with a
      hollow fibre membrane oxygenator. Four groups of pig livers were studied using
      three different liver flushing solutions [Ringer's lactate, ELOHES, and
      University of Wisconsin (UW)] and two different oxygenation modalities. Liver
      function tests and histological studies were done. Our results revealed that a
      high partial oxygen pressure (PO2) level was deleterious to the ultrastructural
      elements of hepatocytes, in particular to the mitochondria. It was also
      associated with deficient metabolic performance, i.e., poor bile production and
      lack of aerobic metabolism. Normal blood gas values could be obtained with the
      use of air for liver oxygenation. Flushing of the liver with Ringer's lactate or
      a macromolecular solution such as ELOHES was associated with severe liver cell
      injuries, as reflected by a marked rise in liver enzymes and histological
      lesions. Satisfactory results were obtained when UW solution was used for liver
      harvesting. We conclude that an appropriate liver preservation solution, normal
      blood gas values, and normal physiological arterio-portal pressure and blood flow
      are essential for appropriate liver function with preservation of liver
      architecture and of hepatocyte ultrastructures. Total bilirubin in bile and
      Factor V are sensitive indicators of good liver function.

PMID- 9249942
TI  - Primary bronchogenic carcinoma in recipients of heart transplants.
AB  - With the exception of carcinomas of the skin and lip, carcinoma of the bronchus
      is the most common carcinoma that afflicts recipients of solid organ grafts. Of
      859 tumors occurring in 830 recipients of thoracic organs reported to the
      Cincinnati Tumor Transplant Registry, 242 were carcinomas and 68 of these were
      bronchogenic carcinomas, which therefore made up 8% of the overall total. There
      are, however, relatively few reports of heart transplant patients with
      bronchogenic carcinoma in the literature. We present details of four patients who
      developed this malignancy out of a total of 196 patients who survived and have
      been followed up for more than 3 months at our center, an incidence of 2%. The
      mean period from the time of transplant to diagnosis of malignancy was 58 months
      (range 11-82 months). The histology was squamous or anaplastic in three cases,
      and adenocarcinoma in one. Immunosuppressive therapy was reduced in all cases.
      Resection was carried out in two patients (both of whom died 6 and 11 months
      later, respectively), resection was combined with chemotherapy and radiation in
      one patient (alive 15 months later), and therapy consisting of radiation alone
      was given to one patient (died within 1 month). We conclude that bronchogenic
      carcinoma is relatively common in patients with heart transplants and that it has
      a poor prognosis.

PMID- 9249944
TI  - Renal responses to exercise in heart and kidney transplant patients.
AB  - There is a lack of information about renal responses in heart and kidney
      transplant patients after intense physical exercise. Eleven heart and ten kidney
      transplant recipients, as well as two control groups of healthy subjects, were
      given a maximum exercise test on a bicycle ergometer. One control group was also
      given a moderate load corresponding to the peak load of the kidney transplant
      group. Blood and urine samples were collected before and after exercise and
      assayed for lactate, creatinine, total protein, and albumin. The glomerular
      filtration rate remained stable at the end of exercise in the transplant
      patients, while there was a slight (17%) decrease in the control group. Albumin
      excretion rates after maximum exercise attained a mean of 237 micrograms.min-1 in
      the control group and a mean of 45 and 16 micrograms.min-1, respectively, in the
      heart and kidney groups. Postexercise proteinuria seemed to be related to the
      absolute intensity of the event, but kidney transplant patients showed a reduced
      effect as compared to heart transplant patients. We conclude that short-term,
      maximum exercise in heart and kidney transplant recipients is not detrimental to
      kidney function.

PMID- 9249943
TI  - Effect of machine perfusion preservation on delayed graft function in non-heart
      beating donor kidneys--early results.
AB  - The functioning of non-heart-beating (NHB) donor kidneys upon transplantation is
      often delayed. To evaluate the effect of preservation by machine perfusion (MP)
      on early post-transplant function, 37 NHB donor kidneys were compared to 74
      matched heart-beating (HB) donor kidneys preserved by cold storage (CS). The NHB
      donor kidneys were subject to 49 +/- 34 min of warm ischemia. Delayed function
      (DF) and primary nonfunction (PNF) rates were significantly higher for NHB than
      for HB donor kidneys (49% and 19% vs 34% and 7%, respectively). Consequently,
      renal function was impaired but recovered within 6 months. MP could not eliminate
      the differences in DF rate between NHB and HB donor kidneys. However, NHB donor
      kidneys preserved by MP showed less DF than that reported in kidneys preserved by
      CS. This suggests that MP has a beneficial effect on ischemically damaged
      kidneys. The similar results observed with category 2 and category 3 NHB donors
      also suggest this effect. The high PNF rate emphasizes the need for viability
      tests that prevent the transplantation of nonviable organs. We conclude that MP
      alone is not sufficient to reduce DF and PNF rates in NHB donor kidneys.

PMID- 9249945
TI  - Eradication of minimal residual disease during graft-versus-host reaction induced
      by abrupt discontinuation of immunosuppression following bone marrow
      transplantation in a patient with Ph1-ALL.
AB  - We observed a patient in whom graft-versus-host disease (GVHD) appeared to induce
      a positive effect. This 32-year-old male with Philadelphia chromosome-positive
      acute lymphoblastic leukemia received a bone marrow transplant (BMT) from an HLA
      identical sibling donor. We analyzed the bone marrow with the reverse
      transcriptase-polymerase chain reaction to screen for the minor bcr/abl
      transcript, which indicates the presence of minimal residual disease (MRD). MRD
      was present in the pre- and post-transplant phases. There was no evidence of
      acute GVHD by post-transplant day 45. We abruptly discontinued the
      immunosuppressive therapy in an attempt to eliminate MRD by inducing an
      antileukemic reaction during GVHD. GVHD associated with diarrhea and liver
      dysfunction developed on day 64. On day 105, MRD disappeared and GVHD was treated
      with prednisolone and cyclosporin. The disappearance of MRD may have been due to
      the graft-versus-leukemia (GVL) effect mediated by the alloimmune response of
      donor T lymphocytes. These findings suggest that induction of the GVL effect may
      be useful for eliminating MRD after BMT in leukemia patients at high risk of
      recurrence of the disease.

PMID- 9249946
TI  - Tacrolimus (FK506) malabsorption: management with fluconazole coadministration.
AB  - We report the use of fluconazole to control primary immunosuppressive management
      with tacrolimus in a 9-year-old liver transplant recipient. Progressive increases
      in the doses of both cyclosporin (up to 20 mg/kg/day) and, subsequently,
      tacrolimus (up to 60 mg/day) failed to maintain immunosuppressive levels of both
      agents. After excluding poor compliance, drug interactions and analytical
      problems and identifying poor bioavailability (< 2.6%) and rapid clearance (4.2
      l/h), fluconazole (100 mg/day) was initiated to inhibit tacrolimus metabolism and
      consistent therapeutic blood levels of tacrolimus were achieved. However, graft
      function had deteriorated irrevocably and retransplantation was performed.
      Simultaneous use of tacrolimus (5 mg/day) and fluconazole (100 mg/day) maintained
      immunosuppression after transplantation. Three weeks later, obstruction of the
      Roux loop caused deteriorating liver function and tacrolimus blood levels fell.
      After correction at laparotomy, stabilisation was achieved and discharge was
      possible on 5 mg tacrolimus b.i.d. plus fluconazole (100 mg).

PMID- 9249947
TI  - Reuse of a transplanted liver.

PMID- 9249948
TI  - Chitosan N-sulfate. A water-soluble polyelectrolyte.
AB  - Chitosans having degrees of acetylation (da) of 0.04, 0.10, and 0.22,
      respectively, were N-sulfated under a variety of reaction conditions. The
      derivatives obtained ranged in degree of sulfation (ds) from 0.4 to 0.86 (+/
      0.05). All were soluble in water, and the rheological properties of their
      solutions varied markedly with da and ds values. Both ionic strength and pH had
      an effect on their solubility properties, and also on interactions that they
      exhibited with O-(carboxymethyl)cellulose, xanthan gum, and heparin. Being
      compatible with other polyelectrolytes such as these, the chitosan derivatives
      may be useful in some aqueous formulations.

PMID- 9249949
TI  - Synthesis of acylated methyl beta-D-xylopyranosides and their enzymic
      deacylations by rabbit serum esterases.
AB  - Selective pivaloylations of methyl beta-D-xylopyranoside have been studied under
      various reaction conditions. Partially pivaloylated products were submitted to
      additional acetylations. The structures were established by 1H NMR spectroscopy.
      Representatives of acylated methyl beta-D-xylopyranosides (acyl being pivaloyl,
      acetyl, or a combination of both) were submitted to hydrolysis catalyzed by
      rabbit serum and esterases isolated from rabbit serum.

PMID- 9249950
TI  - Direct preparation of cyclodextrin monophosphates.
AB  - Aqueous solutions of cyclodextrins and inorganic metaphosphate at pH 4, upon
      drying and subsequent warming, produce mixtures of isomeric monophosphate esters
      which are amenable to separation by anion-exchange chromatography. The products
      are characterised by enzymatic, mass, and NMR spectroscopic analysis. The
      methodology provides a route to these derivatives by a single reaction.

PMID- 9249951
TI  - Gram-scale synthesis of recombinant chitooligosaccharides in Escherichia coli.
AB  - Cultivation of Escherichia coli harbouring heterologous genes of oligosaccharide
      synthesis is presented as a new method for preparing large quantities of high
      value oligosaccharides. To test the feasibility of this method, we successfully
      produced in high yield (up to 2.5 g/L) penta-N-acetyl-chitopentaose (1) and its
      deacetylated derivative tetra-N-acetyl-chitopentaose (2) by cultivating at high
      density cells of E. coli expressing nodC or nodBC genes (nodC and nodB encode for
      chitooligosaccharide synthase and chitooligosaccharide N-deacetylase,
      respectively). These two products were easily purified by charcoal adsorption and
      ion-exchange chromatography. One important application of compound 2 could be its
      utilisation as a precursor for the preparation of synthetic nodulation factors by
      chemical acylation.

PMID- 9249952
TI  - Isolation and structure elucidation of a highly haemolytic saponin from the Merck
      saponin extract using high-field gradient-enhanced NMR techniques.
AB  - Saponins SAPO50 and SAPO30, of which SAPO50 is highly haemolytic, have been
      isolated from the commercial Merck Saponin. Their structures have been determined
      exclusively by high-field gradient-enhanced NMR methods. The 1H and 13C NMR
      spectra of these saponins in pyridine-deuterium oxide have been assigned by
      homonuclear and heteronuclear correlation experiments. Anomeric configurations
      were obtained by combined use of 1JCH, 3JH-1.H-2, and 1D-NOESY data. Sugar
      residues were identified by use of 3JHH values obtained from their subspectra
      recorded using an optimized 1D-zeta-TOCSY sequence. Linkage assignments were made
      using the ge-HMBC and 1D-NOESY spectra. This study shows that SAPO50 represents a
      hitherto undescribed saponin with the following structure: 3-O-beta-D
      xylopyranosyl-(1-->3)-[beta-D-galactopyranosyl- (1-->2)]-beta-D
      glucuronopyranosyl gypsogenin 28-O-(6-deoxy-beta-D-glucopyranosyl)-(1-->4)-[beta
      D-xylopyranosyl-(1--> 3)- beta-D-xylopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl
      (1-->2)-beta-D- fucopyranoside. SAPO30, however, corresponds to a saponin
      previously described [D. Frechet, B. Christ, B. Monegier du Sorbier, H. Fischer,
      and M. Vuilhorgne, Phytochemistry, 30 (1991) 927-931].

PMID- 9249953
TI  - The structure of the capsular polysaccharide from Klebsiella type 52, using the
      computerised approach CASPER and NMR spectroscopy.
AB  - The structure of the capsular polysaccharide from Klebsiella type 52 has been
      elucidated using an improved and extended version of the computerised approach
      CASPER and NMR spectroscopy as principal methods. A previous suggestion to the
      structure but without the anomeric prefixes, could be shown correct [H. Bjorndal
      et al., Carbohydr. Res., 31 (1973) 93-100]. The polysaccharide has a
      hexasaccharide repeat with the following structure: [formula: see text]

PMID- 9249954
TI  - Differential release of proteoglycans during human B lymphocyte maturation.
AB  - Proteoglycans interact with soluble proteins such as growth factors and thereby
      regulate extracellular signals. During B lymphocyte maturation, secretion of
      proteoglycans may be functionally related to the different requirements of the
      respective maturation stage. In order to address this question we compared
      structures of proteoglycans released by three B lymphocyte lines which correspond
      to different maturation stages. Plasma-cell type U266 cells secreted the largest
      proteoglycans (150 kDa), followed by mature B cells JOK-1 (130 kDa) and pre-B
      cells Nalm 6 (90 kDa). On average, secreted proteoglycans carried four
      glycosaminoglycan chains with molecular masses ranging each from 32 kDa (U266) to
      23 kDa (Nalm 6). All three cell lines secreted more than 90% of their
      proteoglycans possessing chondroitin sulfate chains having chondroitin-4-sulfate
      (delta Di-4S) as the prevalent disaccharide unit. In these proteochondroitin
      sulfates, unsulfated chondroitin (delta Di-0S) was present in smaller quantities
      and chondroitin-6-sulfate (delta Di-6S)-containing proteoglycan was released only
      by Nalm 6 and U266 cells. Cell line Nalm 6 exclusively produced proteochondroitin
      sulfate, whereas in culture medium of JOK-1 and U266 a small amount of
      proteoheparan sulfate was found also. In all three cell lines, treatment with
      chondroitinase ABC released a protein of 30 kDa and chemical deglycosylation
      resulted in a core protein of 21 kDa. In addition to pure proteochondroitin
      sulfate, a small portion of proteoheparan sulfate with a protein moiety of 30 kDa
      was detected after heparitinase treatment in supernatants of JOK-1 and U266.
      Thus, our results indicate that released proteoglycans may undergo modulations in
      their glycosaminoglycan moieties during B-cell differentiation. This may have
      functional consequences at the level of growth factor regulation.

PMID- 9249955
TI  - Hand preference in infant rhesus macaques (Macaca mulatta).
AB  - In this research we examined hand preference in infant rhesus macaques (Macaca
      mulatta). The subjects were 20 Macaca mulatta, each aged between 4 and 11 months.
      We assessed hand preference using both a unimanual reaching task and a bimanual
      coordination task. In the unimanual reaching task, we presented subjects with
      raisins and noted which hand the animals used to retrieve the food. In the
      bimanual coordination task, we presented the same subjects with plastic tubes
      filled with raisin paste and noted which hand the animals used to hold the tubes
      and which hand the animals used to remove the food. We noted a population-level
      bias toward use of the left hand for both tasks. These results suggest early
      right hemisphere advantage for reaching and bimanual coordination in Macaca
      mulatta, although we acknowledge that this issue needs to be examined more
      directly through neuroimaging procedures such as Positron Emission Tomography
      (PET) or functional Magnetic Resonance Imaging (fMRI). We speculate that early
      right hemisphere advantage contributes to differential patterns of hand
      preference development for unimanual and bimanual action, and that the
      development of hand preference for bimanual coordination is related to the
      emergence of hemispheric specialization for processing species-specific
      vocalizations.

PMID- 9249956
TI  - Acoustic characteristics of naturally occurring cries of infants with "colic".
AB  - Although infantile colic has long been defined by a perceived excessive amount of
      crying, acoustic attributes of the cry sound may also contribute to perceptions
      that this early social behavior is excessive or problematic. From an original
      sample of 76 infants (38 infants referred to physicians for problematic crying,
      or "colic," and 38 pair-matched comparison infants), 48 infants who produced
      naturally occurring cry bouts both before and after an evening feeding were
      studied: 11 infants with Wessel's colic, 15 infants with non-Wessel's colic, and
      22 comparison infants. Standard and vociferous cry segments were selected from up
      to 2 min of tape-recorded crying for spectrum analysis. Vociferous cry segments
      had a longer duration, a higher fundamental frequency, and a greater percentage
      of dysphonation than did standard segments. No differences between infant groups
      were found in cries before feeding. After feeding, infants who were problematic
      criers, independent of Wessel's criteria, showed a greater percentage of
      dysphonation in the vociferous cry segment than did comparison infants. This
      finding resulted from a decrease in dysphonation in the cries of comparison
      infants after feeding and an increase in those of infants with non-Wessel's
      colic. The dominant frequency also increased after feeding in the vociferous
      cries of infants with Wessel's colic, resulting in these infants having higher
      pitched cries after feeding than infants in the other 2 groups. Results indicate
      that infants who are perceived to have problematic crying have objectively
      different acoustic features in their cry sounds that are particularly aversive,
      and that complaints about excessive crying cannot be accounted for simply on the
      basis of reporting bias in overly concerned or emotionally labile parents.

PMID- 9249957
TI  - Why dogs have puppies and cats have kittens: the role of birth in young
      children's understanding of biological origins.
AB  - Three studies examined young children's understanding of the biologically causal
      role of birth in determining animal properties and species kind identity. In
      Studies 1 and 2, 4- to 7-year-olds and adults were told stories in which a baby
      was born to an animal of one species (e.g., a horse) but was adopted and raised
      by an animal of another species (e.g., a cow). In Study 1, children were asked to
      judge which parent the baby would resemble on a set of physical properties and
      beliefs. The majority of children were unable to say that the baby would resemble
      the birth parent on physical properties but share the beliefs of the adoptive
      parent. These results indicate that children were not using domain-specific
      causal understandings to reason about the origins of these properties. In Study
      2, however, when asked to explicitly predict the kind of the baby, even 5-year
      olds were able to reliably judge that the baby would be of the same species kind
      as the birth parent rather than the adoptive parent. This result suggests that
      children do understand at some level that birth determines species kind. Study 3
      examined further the extent to which knowledge about birth influenced children's
      inferences about properties. Five-year-olds were asked to judge whether a baby
      would share a set of physical and nonphysical properties with its mother or its
      father. The results showed that children who knew the factual information about
      where babies come from (i.e., inside mommies' tummies) were more likely to
      attribute the mother's properties to the baby than the father's, regardless of
      whether the properties were physical or nonphysical. But this finding was true
      only if the property of one of the parents was not inherently more desirable or
      true than that of the other parent. In sum, the results of these 3 studies
      indicate that knowledge of birth does play a role in children's inferential
      reasoning, even for 5-year-olds, but that that role is not domain-specific. The
      implications for children's understanding of biological inheritance are
      discussed.

PMID- 9249958
TI  - From here and now to there and then: the development of displaced reference in
      homesign and English.
AB  - An essential function of human language is the ability to refer to information
      that is spatially and temporally displaced from the location of the speaker and
      the listener, that is, displaced reference. This article describes the
      development of this function in 4 deaf children who were not exposed to a usable
      conventional language model and communicated via idiosyncratic gesture systems,
      called homesign, and in 18 hearing children who were acquiring English as a
      native language. Although the deaf children referred to the nonpresent much less
      frequently and at later ages than the hearing children, both groups followed a
      similar developmental path, adding increasingly abstract categories of displaced
      reference to their repertoires in the same sequence. Caregivers in both groups
      infrequently initiated displaced reference, except with respect to communication
      about past events. Despite the absence of a shared linguistic code, the deaf
      children succeeded in evoking the non-present by generating novel gestures, by
      modifying the context of conventional gestures, and by pragmatic means. The
      findings indicate that a conventional language model is not essential for
      children to be able to extend their communication beyond the here and now.

PMID- 9249959
TI  - The relation between individual differences in fantasy and theory of mind.
AB  - The relation between early fantasy/pretense and children's knowledge about mental
      life was examined in a study of 152 3- and 4-year-old boys and girls. Children
      were interviewed about their fantasy lives (e.g., imaginary companions,
      impersonation of imagined characters) and were given tasks assessing their level
      of pretend play and verbal intelligence. In a second session 1 week later,
      children were given a series of theory of mind tasks, including measures of
      appearance-reality, false belief, representational change, and perspective
      taking. The theory of mind tasks were significantly intercorrelated with the
      effects of verbal intelligence and age statistically controlled. Individual
      differences in fantasy/pretense were assessed by (1) identifying children who
      created imaginary characters, and (2) extracting factor scores from a combination
      of interview and behavioral measures. Each of these fantasy assessments was
      significantly related to the theory of mind performance of the 4-year-old
      children, independent of verbal intelligence.

PMID- 9249960
TI  - Temperament and parenting antecedents of individual differences in three-year-old
      boys' pride and shame reactions.
AB  - To examine individual differences in pride and shame reactions of 3-year-olds and
      their temperamental and parenting antecedents, 110 boys were studied at ages 36
      and 37 months in a "rigged" achievement situation. After being trained to
      complete explicitly stipulated "easy" and "difficult" tasks before a buzzer
      sounded, success and failure were manipulated by artificially "rigging" how much
      time the child had to work on these tasks. Children's facial, verbal, and
      postural reactions to success and failure were composited to create pride scores
      following success and shame scores following failure. As expected, pride
      reactions were greater following success on the difficult than on the easy task,
      and shame reactions were greater following failure on the easy than on the
      difficult task. Early temperament (at 12/13 months) proved unrelated to pride and
      shame. With respect to parenting, measurements composited across 15, 21, 27, and
      33 months showed that mothers and fathers who were more positive in their
      parenting had children who displayed less pride, and that children whose parents
      (especially mothers) were more negative in their parenting evinced less shame.
      These counterintuitive findings are discussed in terms of differences between
      assessments of parenting obtained in this investigation of parenting antecedents
      and those obtained in other studies of parental responses in the achievement
      situation itself. Directions for future research are outlined.

PMID- 9249961
TI  - The consistency and concomitants of inhibition: some of the children, all of the
      time.
AB  - Toddlers displaying extremely inhibited behavior may be at risk for becoming
      socially withdrawn. However, behavioral inhibition may be a multifaceted
      characteristic, and its concurrent relation to toddler wariness with peers has
      not been examined. In this study, 108 toddlers (54 females) and their mothers
      were observed in novel situations involving unfamiliar settings, adults, and
      peers. Vagal tone, temperament, separation-reunion behavior, and maternal
      oversolicitousness also were assessed. There was little consistency of inhibited
      behavior across the 3 situations. Consistently inhibited toddlers had fearful
      temperaments, showed distress following maternal separation, and had mothers who
      were warm and controlling but unresponsive to children's cues during interaction.
      Toddlers with highly fearful temperaments and highly oversolicitous mothers were
      the most inhibited across contexts.

PMID- 9249962
TI  - Predicting children's friendship status from their dyadic interaction in
      structured situations of potential conflict.
AB  - Dyads of 8-year-old friends identified by sociometric friendship nominations were
      followed through the end of the school year to determine if they remained
      friends. These dyads as well as a control group of nonfriends were observed while
      participating in two structured tasks designed to stimulate real life social
      situations of potential conflict. When negotiating the sharing of an object,
      friends made more proposals than nonfriends, spent more time negotiating, and
      compromised more in making their counterproposals. Compared with dyads in which
      the friendship did not continue through the end of the school year, dyads of
      continuing friends exhibited greater sensitivity in their negotiations. During a
      fast-paced, competitive game, friends engaged in more competitive behavior and
      followed the rules more closely than did nonfriends. However, behavior in this
      game was unrelated to the continuation of friendship.

PMID- 9249963
TI  - Parenting styles, adolescents' attributions, and educational outcomes in nine
      heterogeneous high schools.
AB  - This article examined the contemporaneous and predictive relations between
      parenting styles, adolescents' attributions, and 4 educational outcomes. Data
      were collected from adolescents attending 6 high schools in California and 3 high
      schools in Wisconsin during the 1987-1988 and 1988-1989 school years. The results
      of path analyses partially confirmed the central hypotheses. Adolescents who
      perceived their parents as being nonauthoritative were more likely than their
      peers to attribute achievement outcomes to external causes or to low ability.
      Furthermore, the higher the proportion of dysfunctional attributions made for
      academic successes and failures, the lower the levels of classroom engagement and
      homework 1 year later. Although adolescents' attributional style provided a
      bridge between parenting style and 2 educational outcomes, it did not fully
      explain the impact of parenting on those outcomes. Additional analyses within
      gender and ethnic subgroups reinforced the overall pattern of findings observed
      within the entire sample.

PMID- 9249965
TI  - Social pretend play in Korean- and Anglo-American preschoolers.
AB  - Ninety-two preschoolers (46 Anglo- and 46 Korean-American) were observed during
      free play activities and videotaped in an experimental toy play setting. Cultural
      differences were examined in the frequency of social pretend play, communicative
      strategies, and pretend play themes. Anglo-American children engaged in more
      pretend play during free play activities than Korean-American children. In the
      experimental setting, there were no cultural differences in the frequency of
      pretend play; however, there were significant differences in children's
      communicative strategies and in their play themes. Korean-American children's
      play included everyday activity and family role themes, whereas Anglo-American
      children enacted danger in the environment and fantastic themes. Anglo-American
      children described their own actions, rejected their partners' suggestions, and
      used directives, whereas Korean-American children described their partners'
      actions and used tag questions, semantic ties, statements of agreement, and
      polite requests. The findings suggest that play is a common activity for most
      children. However, the thematic content and the communicative strategies used to
      structure and maintain pretend play are influenced by culture.

PMID- 9249964
TI  - Social categorization and the formation of intergroup attitudes in children.
AB  - The study was designed to test several hypotheses derived from intergroup theory
      concerning the effects of the presence of a novel social category on the
      formation of intergroup attitudes. Elementary school children (N = 61; aged 6-9)
      were given measures of classification skill and self-esteem and assigned to 1 of
      3 types of school classrooms in which teachers made: (1) functional use of "blue"
      and "yellow" groups assigned on the basis of a biological attribute, (2)
      functional use of "blue" and "yellow" groups assigned on the basis of a random
      drawing, or (3) no explicit groups (despite the presence of blue and yellow
      groups). After 4 weeks, children completed measures of intergroup attitudes and
      behavior. As predicted, the functional use of color groups affected children's
      attitudes toward group members, with children showing consistent biases favoring
      their own group. Children with higher levels of self-esteem showed higher levels
      of intergroup stereotyping.

PMID- 9249966
TI  - Personal storytelling as a medium of socialization in Chinese and American
      families.
AB  - The goal of this study was to determine how personal storytelling functions as a
      socializing practice within the family context in middle-class Taiwanese and
      middle-class European American families. The data consist of more than 200
      naturally occurring stories in which the past experiences of the focal child,
      aged 2,6, were narrated. These stories were analyzed at 3 levels: content,
      function, and structure. Findings converged across these analytic levels,
      indicating that personal storytelling served overlapping yet distinct socializing
      functions in the 2 cultural cases. In keeping with the high value placed on
      didactic narrative within the Confucian tradition, Chinese families were more
      likely to use personal storytelling to convey moral and social standards.
      European American families did not treat stories of young children's past
      experiences as a didactic resource but instead employed stories as a medium of
      entertainment and affirmation. These findings suggest not only that personal
      storytelling operates as a routine socializing practice in widely different
      cultures but also that it is already functionally differentiated by 2,6.

PMID- 9249968
TI  - In vitro evaluation of antifungal properties of 8.O.4'-neolignans.
AB  - Eighteen racemic 8.O.4'-neolignans with six different substitution patterns in
      rings A and B, in their ketone and in their erythro and threo alcoholic forms,
      were evaluated for antifungal activity by the agar dilution method. Only the
      alcohols exhibited a broad spectrum of activities against Microsporum canis,
      Microsporum gypseum, Tricophyton mentagrophytes, Tricophyton rubrum, and
      Epidermophyton floccosum. (+/-)-erythro-3,4-(methylenedioxy) -7-hydroxy-1'-allyl
      3',5'-dimethoxy-8.O.4'-neolignan (11) was the most active compound in the series,
      and E. floccosum was the most susceptible species.

PMID- 9249969
TI  - RKS-1778, a new mammalian cell-cycle inhibitor and a key intermediate of the
      [11]cytochalasin group.
AB  - In the course of screening for the mammalian cell-cycle inhibitors, we have
      isolated a new [11]cytochalasin, RKS-1778 (1), and epoxycytochalasin H (2) from a
      fungus, Phoma sp. SNF-1778. The structure of 1 was determined to be 21-acetoxy-18
      hydroxy-10-phenyl-5,6,16,18- tetramethyl[11]cytochalasa-6,13,19-trien-1-one, one
      the basis of spectroscopic methods, including 1H- and 13C-2D NMR techniques, RKS
      1778 (1) may be a precursor of 2 and the key direct product of a proposed
      biosynthetic intramolecular Diels-Alder reaction. Both 1 and 2 completely
      arrested the cell-cycle progression of tsFT210 cells in the M phase at
      concentrations of 2.1 and 2.0 microM, respectively.

PMID- 9249970
TI  - Michellamines D-F, new HIV-inhibitory dimeric naphthylisoquinoline alkaloids, and
      korupensamine E, a new antimalarial monomer, from Ancistrocladus korupensis.
AB  - New monomeric (korupensamine E, 6) and dimeric (michellamines D-F, 7-9)
      naphthylisoquinoline alkaloids have been isolated from exracts of the tropical
      liana Ancistrocladus korupensis. Structures were determined by spectroanalytical
      methods, and stereochemistry was defined through NOE correlations, chemical
      degradation, and CD spectroscopy. Michellamines D-F exhibited in vitro HIV
      inhibitory activity comparable to michellamine B, and korupensamine E exhibited
      in vitro antimalarial activity comparable to korupensamines A-D.

PMID- 9249971
TI  - Study of the acid-catalyzed isomerization of dihydroveatchine.
AB  - A study of the acid-catalyzed isomerization of dihydroveatchine (5) resulted in
      the isolation of a single major compound, the aldehyde 6. Structure 6 has been
      derived from its spectral data. Reduction of 6 with NaBH4 gave compound 7, which
      was characterized through detailed NMR studies including 1D, 2D, and selective
      INEPT experiments, as well as preparation of its mono- and bis(p-nitrobenzoyl)
      derivatives 8 and 9. A plausible mechanism for the formation of 6, derived from
      the spectral data of the isomerized product obtained by deuterium labeling, is
      reported. Interestingly, the acid-catalyzed isomerization products of the allylic
      alcohols garryfoline (1) and dihydroveatchine (5) are different and appear to be
      dependent on the configurational orientation of the C(15) hydroxyl group.
      Unambiguous NMR chemical shift assignments for 5 are also reported.

PMID- 9249972
TI  - In vitro and in vivo antiplasmodial activity of cryptolepine and related
      alkaloids from Cryptolepis sanguinolenta.
AB  - Three different extracts and four alkaloids from the root bark of Cryptolepis
      sanguinolenta have been assessed in vitro against Plasmodium falciparum D-6
      (chloroquine-sensitive strain), K-1, and W-2 (chloroquine-resistant strains).
      Cryptolepine (1) and its hydrochloride (2), 11-hydroxycryptolepine (3), and
      neocryptolepine (5) showed a strong antiplasmodial activity against P. falciparum
      chloroquine-resistant strains. Quindoline (4) was less active. The highest
      activity was obtained with compound 1. In vivo tests on infected mice showed that
      cryptolepine (1), when tested as its hydrochloride (2), exhibited a significant
      chemosuppressive effect against Plasmodium berghei yoelii and Plasmodium berghei,
      berghei, while 1 had the same effect against P. berghei yoelii only. Compounds 3
      and 4 did not show activity in this in vivo test system.

PMID- 9249973
TI  - Alternatamides A-D: new bromotryptamine peptide antibiotics from the Atlantic
      marine bryozoan Amathia alternata.
AB  - Four new bromotryptamine peptides, alternatamides A-D (1-4), have been isolated
      from the Atlantic bryozoan Amathia alternata. The structures of the
      alternatamides were assigned primarily on the basis of 2D NMR data. The absolute
      stereochemistry of the N-methylleucine amino acid was shown to be L (2'S) by
      hydrolysis and comparison with standards. The alternatamides show modest
      antibacterial activities against several Gram-positive bacteria.

PMID- 9249974
TI  - Sodwanones K, L, and M; new triterpenes from the marine sponge Axinella weltneri.
AB  - Three new triterpenes, sodwanones M, K, and L (4, 5, 6), together with three
      known sodwanones (A, B, and D) have been isolated from the sponge Axinella
      weltneri from the Comoros Islands, in the Indian Ocean. The three new structures
      were determined by interpretation of NMR spectra and, in the case of sodwanone K,
      also by oxidation to the known sodwanone D. Sodwanone M, the major isolated
      compound, was found to be cytotoxic to P-388 murine leukemia cells at a
      concentration of 1 microgram/mL.

PMID- 9249975
TI  - Inhibitory effect of dehydroevodiamine and evodiamine on nitric oxide production
      in cultured murine macrophages.
AB  - Possible antiinflammatory effects of dehydroevodiamine (1) and evodiamine (2)
      were examined by assessing their effects on NO production in the murine
      macrophage-like cell line RAW 264.7. The results indicated that both 1 and 2
      inhibited the IFN-gamma/LPS-stimulated NO production in a concentration-dependent
      manner. However, 1 appeared to inhibit NO production by interfering not only with
      the priming signal initiated by IFN-gamma but also with iNOS protein synthesis,
      while 2 affected the former only.

PMID- 9249976
TI  - (2E,9E)-pyronaamidine 9-(N-methylimine), a new imidazole alkaloid from the
      northern Mariana islands sponge Leucetta sp. cf. chagosensis.
AB  - A new imidazole alkaloid, (2E,9E)-pyronaamidine 9-(N-methylimine) (4), was
      isolated along with the known compounds pyronaamidine (3) and kealiiquinone (5)
      from the yellow sponge Leucetta sp. cf. chagosensis collected near the Island of
      Rota, Northern Mariana Islands. Single-crystal X-ray diffraction analysis allowed
      the unambiguous assignment of the structure of compound 4, including the position
      of the exchangeable proton and the geometry of the two imino double bonds.
      Compound 4 exhibited mild cytotoxicity toward the A-549, MCF-7, and HT-29 human
      tumor cell lines.

PMID- 9249977
TI  - Brasilidine A, a new cytotoxic isonitrile-containing indole alkaloid from the
      actinomycete Nocardia brasiliensis.

PMID- 9249979
TI  - Kawaguchipeptin B, an antibacterial cyclic undecapeptide from the cyanobacterium
      Microcystis aeruginosa.
AB  - Kawaguchipeptin B, an antibacterial cyclic undecapeptide, was isolated from the
      cultured cyanobacterium Microcystis aeruginosa (NIES-88). Its structure was
      elucidated as 1 on the basis of 2D NMR data and chemical degradation.
      Kawaguchipeptin B (1) inhibited the growth of the Gram-positive bacterium
      Staphylococcus aureus at a concentration of 1 microgram/mL (MIC).

PMID- 9249978
TI  - New indole derivatives with free radical scavenging activity from Agrocybe
      cylindracea.
AB  - Two new indole derivatives were isolated as free radical scavengers from the MeOH
      extract of Agrocybe cylindracea. The structures of these compounds were
      determined to be 6-hydroxy-1H-indole-3-carboxaldehyde (1) and 6-hydroxy-1H-indole
      3-acetamide (2) on the basis of spectroscopic studies. Compounds 1 and 2
      inhibited lipid peroxidation in rat liver microsomes, with IC50 values of 4.1 and
      3.9 micrograms/mL, respectively.

PMID- 9249980
TI  - Isolation and characterization of 1,3-dimethylisoguanine from the Bermudian
      sponge Amphimedon viridis.
AB  - The new compound 1,3-dimethylisoguanine has been isolated and characterized from
      the Bermudian sponge Amphimedon viridis. Chemical conversion of the natural
      product to theophylline and 2D NMR methods were used to determine the position of
      the methyl groups on the purine ring. Analysis of the mass spectral fragmentation
      pattern allowed assignment of the purine ring as isoguanine.

PMID- 9249981
TI  - 1,3-Dimethylisoguanine, a new purine from the marine sponge Amphimedon viridis.
AB  - A new purine, 1,3-dimethylisoguanine (1), has been isolated from the marine
      sponge Amphimedon viridis and identified by analysis of spectroscopic data.
      Compound 1 increased the contractions obtained by transmural electrical
      stimulation in the guinea pig longitudinal muscle/myenteric plexus in a dose
      dependent manner.

PMID- 9249982
TI  - New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica.
AB  - A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit
      rind led to the isolation of two new lignans named termilignan (1) and
      thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and
      anolignan B (4). All four compounds possessed demonstrable anti-HIV-1,
      antimalarial, and antifungal activity in vitro.

PMID- 9249983
TI  - Asterlingulatosides C and D, cytotoxic triterpenoid saponins from Aster
      lingulatus.
AB  - A further investigation of Aster lingulatus has led to the isolation of two
      additional novel triterpene saponins, asterlingulatoside C [3-O-beta-D
      glucopyranosyl-3 beta, 16 alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D
      xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha- L-
      arabinopyranoside] (1) and asterlingulatoside D [3-O-beta-D-glucopyranosyl-3
      beta,16 alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->3)
      beta-D-xylopyranosyl-(1-->4)-alpha-L- rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside] (2). Elucidation of the structures of 1 and 2 was mainly based
      on FABMS and 1D and 2D homonuclear and heteronuclear NMR techniques. Compounds 1
      and 2 showed good inhibitory activity against DNA synthesis in human leukemia HL
      60 cells with IC50 values of 8.8 and 6.1 microM, respectively.

PMID- 9249985
TI  - Evolutionary consideration on 5-aminolevulinate synthase in nature.
AB  - 5-Aminolevulinic acid (ALA), a universal precursor of tetrapyrrole compounds can
      be synthesized by two pathways: the C5 (glutamate) pathway and ALA synthase. From
      the phylogenetic distribution it is shown that distribution of ALA synthase is
      restricted to the alpha subclass of purple bacteria in prokaryotes, and further
      distributed to mitochondria of eukaryotes. The monophyletic origin of bacterial
      and eukaryotic ALA synthase is shown by sequence analysis of the enzyme.
      Evolution of ALA synthase in the alpha subclass of purple bacteria is discussed
      in relation to the energy-generating and biosynthetic devices in subclasses of
      this bacteria.

PMID- 9249986
TI  - A major jasmonate-inducible protein of sweet potato, ipomoelin, is an ABA
      independent wound-inducible protein.
AB  - Treatment of sweet potato plants cultured in vitro with a vapor of methyl
      jasmonate (MeJA) induced an accumulation in leaves of a large amount of protein
      with an apparent molecular mass of 18 kDa. This protein, designated ipomoelin,
      was purified, and the amino acid sequences of proteolytic fragments were
      determined. Screening a cDNA library of MeJA-treated leaves by oligonucleotide
      probes designed from the peptide sequences identified a clone that could code for
      a polypeptide with 154 amino acids. The deduced amino acid sequence of ipomoelin
      showed an overall amino acid identity of 25% with the salt-inducible SalT protein
      of rice. In addition, the C-terminal 70 amino acid sequence of ipomoelin showed
      about 50% identity with the C-terminal amino acid sequences of seed lectins from
      Moraceae. The gene for ipomoelin was present in a few copies in the genome of
      sweet potato. The mRNA for ipomoelin was detected in leaves and petioles, but not
      in stems and tuberous roots, of sweet potato plants grown in the field.
      Mechanical wounding of leaves induced ipomoelin mRNA both locally and
      systemically, while treatment of leaves with ABA, salt, or a high level of
      sucrose did not induce ipomoelin mRNA. By contrast, ABA-inducible mRNA for
      sporamin was not induced by MeJA. These results suggest that ipomoelin is
      involved in defensive reactions of leaves in response to wounding and that JA
      mediated wound-induction of ipomoelin occurs independently of ABA.

PMID- 9249987
TI  - Association between ion fluxes and defense responses in pea and cowpea tissues.
AB  - The glycopeptide elicitor from a pea pathogen, Mycosphaerella pinodes, induced
      rapid alkalinization and increases in levels of Na+ and K+ ions in the
      extracellular solution upon contact with pea and cowpea tissues. The presence of
      monensin, nigericin, lidocaine, quinidine or phenytoin together with the elicitor
      markedly inhibited these changes, whereas the presence of valinomycin, gramicidin
      D, tetraethylammonium, CsCl and aminopyridine did not. The production of
      phytoalexins in pea and cowpea tissues was also strongly inhibited by the
      simultaneous presence of the former reagents but not of the latter reagents.
      Inhibitory effects on the production of phytoalexins were diminished when
      monensin, nigericin or a Na(+)-channel blocker was applied 3 h after the start of
      treatment with elicitor. Furthermore, orthovanadate and neomycin, which suppress
      defense responses in both tissues, also inhibited the above mentioned changes. By
      contrast, the species-specific suppressor from M. pinodes inhibited the elicitor
      induced release of Na+ and K+ ions from pea tissues, but, conversely, by itself
      it elicited either the defense response or the release of Na+ and K+ ions from
      cowpea tissues. The results indicate that these ion-related changes, in
      particular the efflux of Na+ and K+ ions, might be closely associated with the
      signal transduction system for defense responses at the tissue level.

PMID- 9249988
TI  - Accumulation of 19-kDa plasma membrane polypeptide during induction of freezing
      tolerance in wheat suspension-cultured cells by abscisic acid.
AB  - Suspension-cultured cells derived from immature embryos of winter wheat (Triticum
      aestivum L. cv. Chihoku) were used in experiments designed to obtain clues to the
      mechanism of the ABA-induced development of freezing tolerance. Cultured cells
      treated with 50 microM ABA for 5 d at 23 degrees C acquired the maximum level of
      freezing tolerance (LT50; -21.6 degrees C). The increased freezing tolerance of
      ABA-treated cells was closely associated with the remarkable accumulation of 19
      kDa polypeptides in the plasma membrane. The 19-kDa polypeptide components were
      isolated by preparative gel electrophoresis and were further separated into one
      major (AWPM-19) and other minor polypeptide components by Tricine-SDS-PAGE. N
      terminal amino acid sequence of AWPM-19 was determined, and a cDNA clone encoding
      AWPM-19 was isolated by PCR from the library prepared from the ABA-treated
      cultured cells. The cDNA clone (WPM-1) encoded a 18.9 kDa hydrophobic polypeptide
      with four putative membrane spanning domains and with a high pI value (10.2).
      Expression of WPM-1 mRNA was dramatically induced by 50 microM ABA within a few
      hours. These results suggest that the AWPM-19 might be closely associated with
      the ABA-induced increase in freezing tolerance in wheat cultured cells.

PMID- 9249989
TI  - Inhibition of the stomatal blue light response by verapamil at high
      concentration.
AB  - Blue light-dependent proton pumping in guard cell protoplasts and light-induced
      stomatal opening in the epidermis were inhibited by 1 mM verapamil, a Ca2+
      channel blocker. Proton pumping and stomatal opening induced by fusicoccin, an
      activator of plasma membrane proton pump, were not inhibited by verapamil. These
      results suggest that verapamil inhibits blue light signaling in guard cells
      without inhibiting the pump.

PMID- 9249990
TI  - Identification of new chalcone synthase genes for flower pigmentation in the
      Japanese and common morning glories.
AB  - New cDNA sequences for chalcone synthase (CHS), a key enzyme in the flavonoid
      biosynthesis, were obtained from the Japanese and common morning glories; they
      are more closely related to other CHS sequences than the six previously described
      CHS genes from the same plants. The newly isolated CHS-D gene is abundantly
      expressed in the pigmented flower buds, while its expression is drastically
      reduced in the white flower buds. Thus CHS-D appears to produce major CHS
      transcripts for flower pigmentation.

PMID- 9249991
TI  - Changes in targeting efficiencies of proteins to plant microbodies caused by
      amino acid substitutions in the carboxy-terminal tripeptide.
AB  - It has been demonstrated that the carboxyl terminus of microbody enzymes
      functions as a targeting signal to microbodies in higher plants. We have examined
      an ability of 24 carboxy-terminal amino acid sequences to facilitate the
      transport of a cytosolic passenger protein, beta-glucuronidase, into microbodies
      in green cotyledonary cells of transgenic Arabidopsis. Immunoelectron microscopic
      analysis revealed that carboxy-terminal tripeptide sequences of the form
      [C/A/S/P]-[K/R]-[I/L/M] function as a microbody-targeting signal, although
      tripeptides with proline at the first amino acid position and isoleucine at the
      carboxyl terminus show weak targeting efficiencies. All known microbody enzymes
      that are synthesized in a form similar in size to the mature molecule, except
      catalase, contain one of these tripeptide sequences at their carboxyl terminus.

PMID- 9249993
TI  - Bioaffinity layering: a novel strategy for the immobilization of large quantities
      of glycoenzymes.
AB  - A simple strategy for increasing considerably the quantities of glycoenzymes
      immobilized on insoluble supports is described. The strategy that we call
      bioaffinity layering makes use of the multivalent nature of concanavalin A (Con
      A) and the multiple oligosaccharide chains of most glycoenzymes to build
      alternating lectin and glycoenzyme layers on a Sepharose matrix with precoupled
      Con A. Using this procedure, it was possible to increase the amounts of several
      glycoenzymes immobilized on Sepharose and 19.0 mg glucose oxidase could be
      associated with one ml Sepharose matrix after seven Con A/glucose oxidase
      incubation cycles. Bioaffinity layered preparations of glycoenzymes exhibited
      high activities as indicated by very high effectiveness factor (eta) values and
      those of glucose oxidase and invertase exhibited a layer-by-layer increase in
      thermostability. The sensitivity of a flow-through glucose monitoring cartridge
      integrated into a flow injection analysis (FIA) system was enhanced significantly
      by increasing the amount of immobilized glucose oxidase via bioaffinity layering.
      A cartridge bearing six layers of glucose oxidase on Sepharose support was used
      effectively and repeatedly for analysis of medium glucose concentration during a
      fed-batch cultivation of the yeast Saccharomyces cerevisiae.

PMID- 9249995
TI  - The JIM interview. Art Levinson, PhD.
AB  - In the early 1980s several prominent scientists left the hallowed halls of
      respected universities seeking to exploit the revolution occurring in biology in
      an environment devoid of the bureaucratic and political confines of academia. The
      emergence of the biotechnology industry has been marked by both spectacular
      failures and success stories. Genentech was founded in 1976 by biochemist Herbert
      Boyer and venture capitalist Robert Swanson and went public in 1980. In 1995
      Genentech merged with Roche Holdings Ltd., of Basel Switzerland. Distinguished
      from other biotech companies by the varied array of products it has brought to
      market, Genentech has also developed a unique corporate culture embodying many
      traditional academic values. Just as Genentech went public in 1980, Arthur D.
      Levinson, PhD, finished a post-doctoral appointment in Michael Bishop's lab at
      the University of California, San Francisco. Despite the disapproval of
      colleagues, he joined the fledgling company as a senior scientist. Working his
      way though the ranks, Levinson became Vice President of Research Technology in
      1989 and was named President and CEO in 1995. Interviewed at the sprawling
      corporate headquarters in South San Francisco, Levinson reflected on the process
      of high risk science, the benefits of the private sector, and the changing
      relationship between biotech companies and the academic world.

PMID- 9249994
TI  - A stereo-inverting D-phenylglycine aminotransferase from Pseudomonas stutzeri ST
      201: purification, characterization and application for D-phenylglycine
      synthesis.
AB  - D-phenylglycine aminotransferase (D-PhgAT) from a newly isolated soil bacterium,
      Pseudomonas stutzeri ST-201, was purified to electrophoretic homogeneity and
      characterized. The molecular weight (M(r)) of the native enzyme was estimated to
      be 92,000. It is composed of two subunits identical in molecular weight (M(r)) =
      47,500). The isoelectric point (pI) of the native enzyme was 5.0. The enzyme
      catalyzed reversible transamination specific for D-phenylglycine or D-4
      hydroxyphenylglycine in which 2-oxoglutarate was an exclusive amino group
      acceptor and was converted into L-glutamic acid. Neither the D- nor L-isomer of
      phenylalanine, tyrosine, alanine, valine, leucine, isoleucine or serine could
      serve as a substrate. The enzyme was most active at alkaline pH with maximum
      activity at pH 9-10. The temperature for maximum activity was 35-45 degrees C.
      The apparent K(m) values for D-phenylglycine and for 2-oxoglutarate at 35 degrees
      C, pH 9.5 were 1.1 and 2.4 mM, respectively. The enzyme activity was strongly
      inhibited by typical inhibitors of pyridoxal phosphate-dependent enzymes.
      Possible application of this enzyme for synthesis of enantiomerically pure D
      phenylglycine was demonstrated.

PMID- 9249996
TI  - Mechanisms of insulin resistance leading to hypertension: what we can learn from
      experimental models.

PMID- 9249997
TI  - Use of human tissues in research: clarifying clinician and researcher roles and
      information flows.

PMID- 9249999
TI  - Effect of a single ethanol exposure on HIV replication in human lymphocytes.
AB  - BACKGROUND: Alcoholism is known to cause perturbations in cellular and humoral
      immunity, and some data suggest that acute alcohol ingestion enhances HIV
      replication in the lymphocytes of drinkers. METHODS: To study the acute effects
      of alcohol ingestion on HIV replication, oral ethanol (1 g/kg) was administered
      to 12 healthy volunteers in a controlled clinical setting. In vitro replication
      of HIV in the subjects' cultured lymphocytes and changes in lymphocyte phenotypes
      were evaluated. RESULTS: Statistically significant increases in peripheral
      lymphocytes and natural killer cell numbers were identified after the initial
      ethanol trial. HIV replication also increased in the isolated lymphocytes of some
      subjects after ethanol ingestion, but most subjects in the second trial showed
      essentially no changes in any of these parameters. CONCLUSIONS: Our results are
      consistent with either a subtle, study-induced stress-related enhancement in HIV
      replication or significant individual variation in response to ethanol. The
      results do not provide evidence for a general increase in HIV replication in the
      lymphocytes of subjects following a single in vivo ethanol dose of 1 g/kg.

PMID- 9249998
TI  - A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle
      cell disease not in crisis at the time of study.
AB  - BACKGROUND: The painful episodes of sickle cell disease (SCD) involve vaso
      occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen
      carrier, has been shown to support oxygen delivery in animal studies and to be
      safe and well tolerated in normal human volunteers. Therefore, we speculated that
      it might have a therapeutic role in SCD. METHODS: Eighteen adults with SCD who
      were asymptomatic at the time of study were enrolled in a Phase I/II single
      blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose
      was to assess the safety of the material in this patient population. In addition,
      as a surrogate marker of efficacy, each subject underwent a variety of exercise
      tests before and after HBOC-201 was given. RESULTS: All HBOC-201 infusions were
      well tolerated by the study subjects and no evidence of toxicity was noted. In
      addition, there was a significant difference in heart rate response to the
      identical aerobic exercise workload when the study subjects who received HBOC-201
      were compared to the subjects who received placebo (p = 0.0061). CONCLUSIONS:
      HBOC-201 was safely administered to patients with SCD who were not in crisis at
      the time of study. Furthermore, following infusion of the study material,
      subjects with SCD performed the identical aerobic exercise-induced workload with
      an increase in heart rate that was significantly less than the increase observed
      in the subjects who received an infusion of the saline placebo. These safety and
      surrogate efficacy data support the notion that HBOC-201 could have efficacy as a
      treatment for the vasoocclusive episodes of SCD.

PMID- 9250000
TI  - Generation of physician-scientists manpower: a follow-up study of the first 294
      graduates of the Harvard-MIT Program of Health Sciences and Technology.
AB  - BACKGROUND: The MD program of the Harvard-MIT Division of Health Sciences and
      Technology was founded in 1970. One of its goals was the application of the
      academic resources of the two universities to the education of leaders in
      academic medicine and biomedical sciences. METHODS: The first MD class was
      admitted in 1971. Prerequisites for admission are a strong background in
      quantitative sciences and demonstrated interest in research. Research and a
      thesis are obligatory. Enrollment in a PhD program is elective. Questionnaires
      were sent to 293 alumni who graduated from the MD program between 1975 and 1988,
      followed up by letters and telephone calls. RESULTS: By 1988, 296 students had
      graduated, 207 with an MD only, 89 with MD-PhD degrees. Follow-up by
      questionnaires of 293 living graduates (92%), plus indirect data on 11 others,
      revealed that 212 (75%) held faculty appointments in 64 medical schools. Overall,
      73.5% of respondents were engaged in research: 68% of MDs and 86% of MD-PhDs. One
      hundred and four (38%) respondents spent more than 50% of their time on research:
      54 (29%) of MDs and 50 (60%) of MD-PhDs. Seventy-five percent of respondents were
      active in teaching. CONCLUSION: Our experience indicates that both an MD-PhD
      program and a research-oriented MD program are effective in producing physician
      scientists and leaders in academic medicine.

PMID- 9250001
TI  - Comparison of effects of uroguanylin, guanylin, and Escherichia coli heat-stable
      enterotoxin STa in mouse intestine and kidney: evidence that uroguanylin is an
      intestinal natriuretic hormone.
AB  - BACKGROUND: Uroguanylin and guanylin are intestinal peptides that activate a
      receptor-guanylate cyclase, which is also a receptor for Escherichia coli heat
      stable enterotoxin (STa). These peptides may have a role in the body's regulation
      of fluid and electrolytes. METHODS: STa, bioactive guanylin, and bioactive
      uroguanylin were evaluated for effects in: 1) the suckling mouse intestinal fluid
      secretion assay; 2) an in vitro suckling mouse intestinal loop assay; 3) an
      intestinal receptor autoradiography assay; 4) a control or agonist-stimulated
      assay for cGMP response in T84 cells; and 5) an in vivo renal function assay in
      mice. RESULTS: In vivo, orally administered uroguanylin and STa but not guanylin,
      stimulated intestinal fluid secretion. All three peptides activated intestinal
      guanylate cyclase and had common intestinal receptors. In vitro, after
      pretreatment with chymotrypsin, only uroguanylin and STa retained agoinst
      activity. Chymostatin preserved guanylin activity. STa and uroguanylin induced
      diuresis, natriuresis, and kaliuresis. Guanylin was less potent than uroguanylin
      and STa. CONCLUSIONS: The results suggest that the endogenous intestinal
      peptides, uroguanylin and guanylin, regulate water and electrolyte homeostasis
      both through local effects on intestinal epithelia and endocrine effects on the
      kidney.

PMID- 9250003
TI  - A novel model of bacterially-induced acute anterior uveitis in rats and the lack
      of effect from HLA-B27 expression.
AB  - BACKGROUND: Humans with the major histocompatibility antigen B27 (HLA-B27) are
      especially at risk for developing rheumatic disorders such as ankylosing
      spondylitis and Reiter's syndrome. Acute anterior uveitis (AAU) often occurs in
      association with these diseases or in HLA B27 positive individuals without joint
      disease. METHODS: We induced acute anterior uveitis in Lewis rats by a standard
      model, the intraperitoneal injection of 200 micrograms of Escherichia coli
      endotoxin. We also developed a novel model of uveitis secondary to gram-negative
      infection. RESULTS: Transgenic rats that expressed a low copy number of the B27
      gene did not differ statistically from litter mate controls in the intensity of
      anterior uveitis as judged by histology, enumeration of cells in aqueous humor,
      protein in aqueous humor, or slit lamp examination. The majority of rats exposed
      to live Salmonella enteritidis or Yersinia enterocolitica 0:3 using either an
      oral or intravenous route of infection developed anterior uveitis. In contrast to
      the disease induced by endotoxin that is most intense 24 hours after the
      endotoxin challenge, uveitis induced by live bacteria usually began 7 to 9 days
      after exposure to bacterial products, was more often unilateral, persisted for as
      long as 3 weeks, and was sometimes recurrent. The expression of HLA-B27 did not
      appear to influence the incidence or severity of uveitis in B27+ low copy
      heterozygous animals. CONCLUSION: This rat model of AAU should facilitate
      evaluation of bacterial antigenic component(s) involved in the pathogenesis of
      live gram-negative bacteria induced AAU.

PMID- 9250004
TI  - Problems of Treatment of Cancer in the Elderly. Proceedings of an international
      conference. Rome, Italy, June 9-10, 1997.

PMID- 9250002
TI  - Decrease of brain protein kinase C, protein kinase A, and cyclin-dependent kinase
      correlating with pH precedes neuronal death in neonatal asphyxia.
AB  - BACKGROUND: Acidosis, energy depletion, overstimulation by excitatory amino
      acids, and free radical-mediated reactions are the major, current concepts for
      the explanation of damage and death resulting from asphyxia. Impaired protein
      phosphorylation by protein kinase C represents another mechanism incriminated in
      cell death. METHODS: We used a nonsophisticated perinatal asphyxia model to study
      brain (frontal cortex) pH, ATP, protein kinases PKC, PKA, and cyclin-dependent
      kinase. We used o-tyrosine, a marker for hydroxyl radical attack, and LPO 586, a
      spectrophotometric assay, to study lipid peroxidation products. The antioxidant
      enzymes catalase, superoxide dismutase, and glutathione peroxidase were used in
      the frontal cortex. In addition, a cell death ELISA and histology to evaluate
      cell death were performed. RESULTS: Brain pH and protein kinases were decreasing
      with the length of the asphyctic periods, and energy depletion was shown by a
      drop of ATP levels, whereas no evidence for the involvement of free radical
      mediated mechanisms was obtained. Cell death was shown by the cell death ELISA as
      early as 10 minutes after the asphyctic period, and histologically, cell death
      could be revealed but not before day 8 after asphyxia. CONCLUSION: Acidosis
      and/or impaired protein kinases, but not free radical mechanisms, may play a role
      in the pathobiochemistry of cell death in neonatal asphyxia of the rat.

PMID- 9250005
TI  - Epidemiology of cancer in the elderly. Current status and projections for the
      future.
AB  - This paper provides an epidemiologic overview for the international conference,
      "Problems of Treatment of Cancer in the Elderly," Rome, Italy. The current cancer
      burden in the elderly and demographic situation and what can be anticipated in
      coming decades is profiled for the United States with data from epidemiologic
      perspective of cancer and aging. The National Institute on Aging (NIA),
      Geriatrics Program is promoting interest in integrating aging and cancer
      research. In the United States, the cancer burden of the elderly is high and has
      increased over time. Currently, 60% of all malignant tumors occur in the age
      group 65 years and older, 69% of all cancer deaths are in this age group. As the
      U.S. population ages, the needs for cancer control will continue to increase. The
      age segment of the U.S. population is 2.5% (31.1 million). Based on current
      projections by the U.S. Bureau of the Census, by 2030, one in five Americans will
      be 65+, reflecting a proportion of 20.1% of the total population (70.2 million
      persons). The paper describes cancer in the elderly, now and in the future,
      emphasizing several pertinent issues, the comorbidity burden of cancer patients,
      the impact of the expansion of the aged segment of the U.S. population over time,
      and cancer prevalence. Briefly mentioned, also, are two recent research
      announcements initiated by the NIA and cosponsored by the NCI and other NIH
      Institutes, "Aging Women and Breast Cancer", and "Aging, Race, and Ethnicity in
      Prostate Cancer".

PMID- 9250006
TI  - Malignant tumors at very old ages.
AB  - Unselected autopsy findings of nonagerians reviewed by the authors in the last 20
      years, confirm a decline in malignant tumors at very old ages. Two main factors
      are thought to be responsible for this evidence: a less aggressive biological
      behavior of cancer in the oldest old; the crucial role played by comorbidity as
      the cause of death.

PMID- 9250007
TI  - Comorbidity and cancer in the aged: the geriatrician's point of view.
AB  - Demographic trends in Italy and Western countries show a progressive aging of the
      population, which concerns the 80+ segment. The aging population is characterized
      by increased comorbidity and functional decline. The "frail elderly", who has
      problems in a variety of areas, including the physical, cognitive, psychological,
      social and economic ones, represents the paradigm of the emerging demographic and
      epidemiologic reality. In oncology, there is increasing awareness of the impact
      of comorbidity on cancer management in the elderly (including both screening and
      treatment). The Comprehensive Geriatric Assessment represents the only answer to
      such problems, allowing to improve the quality of life, prolong survival and
      maintain functional status.

PMID- 9250008
TI  - Comorbidity and cancer in the aged: the oncologists point of view.
AB  - Cancer in the elderly represents a frequent cause of morbidity and mortality.
      Moreover, older people frequently present comorbid chronic conditions with
      functional limitations and it is not known to what extent the coexistence of
      other disease interferes with referral, diagnosis, therapeutic choice and
      prognosis of elderly cancer patients. Two cooperative studies were conducted. The
      first was aimed to investigate comorbid disease burden and functional limitations
      in older neoplastic and non neoplastic patients and younger neoplastic patients.
      The second is ongoing and aims to evaluate the role of the Comprehensive
      Geriatric Evaluation to optimize the management of elderly cancer patients.

PMID- 9250009
TI  - Medical therapy of solid tumors in the elderly: an update.
AB  - This article explores the medical treatment of solid tumors in older individuals.
      After a brief review of pharmacology of anticancer agents in the elderly we will
      examine the treatment of common neoplasms, such as cancer of the breast, of the
      large bowel and of the prostate.

PMID- 9250010
TI  - Treatment of lymphoma in the elderly: an update.
AB  - Recent studies specifically directed toward assessing the outcome of older
      patients with non-Hodgkin's lymphoma (NHL) indicate that age per se is an
      important and independent prognostic factor for response and survival.
      Prospective studies have addressed therapeutic approaches in these patients.
      Direct comparison of trial results is difficult since different age limits were
      set for the inclusion of patients in study. These studies suggest that older
      patients with aggressive NHL should be treated with curative intent. We report on
      selected prospective clinical trials of the literature and the Aviano Group
      experience in the treatment of NHL in the elderly. In particular we refer our
      data of a randomized study (CHOP vs VMP), conducted within the EORTC Lymphoma
      Group, and the results obtained with chemotherapy and granulocyte colony
      stimulating factor.

PMID- 9250011
TI  - Treatment of multiple myeloma and acute myelogenous leukemia in the elderly: an
      update.
AB  - The optimal management of hematopoietic malignancies in the elderly requires the
      development of specific therapeutic strategies based on the peculiar clinico
      biologic features of aged patients. Multiple myeloma arising in elderly patients
      remains at this time an incurable disease, while attention to supportive therapy
      and palliation can make a great impact on the quality of life. Fortunately
      advances have been made in last years in this field. Therapy at the time of
      diagnosis is usually recommended for patients with symptomatic disease, or for
      those who may be asymptomatic, but have evidence of high tumor burden of a
      biologically aggressive disease, and may be expected to progress and develop
      complications over a short period of time. Melphalan combined with prednisone
      remains the standard therapy choice in elderly patients. Radiotherapy maintains
      an important place in the palliation of destructive bone disease in poorly
      controlled myeloma, particularly in elderly patients. In Acute Myelogenous
      Leukemia, age has been concordantly reported as an adverse prognostic indicator
      in affecting both remission rates and survival. The overall unsatisfactory
      therapeutic results appear connected with host-related factors, and intrinsic
      differences in the biology of leukemia. Patients with standard risk should be
      included in collaborative trials aimed at improving the long-term results of
      conventional therapy. Patients with high risk and unfavorable prognostic factors,
      could be enrolled in controlled studies aimed at better assessing, in the
      elderly, the long term results of newer drug combinations. A watch and wait
      strategy, consisting of transfusion support and leukocytosis control, should be
      limited to patients with extremely poor performance status (PS), very limited
      life-expectancy and/or severe comorbidity displaying unfavorable biologic
      factors, including secondary Acute Myelogenous Leukemia.

PMID- 9250012
TI  - Hematopoiesis and growth factors in elderly cancer patients.
AB  - Hemopoietic Growth Factors (GF) are glycoprotein hormones that regulate the
      proliferation and differentiation of hematopoietic progenitor cells and of mature
      blood cell function. In last years GFs have moved from the laboratory study to
      the clinical area, and most of them have been produced on a large scale through
      recombinant DNA technology. Hemopoiesis and GF sensitivity of marrow cells
      declines with age, impairing the ability of elderly people to increase the
      production of GFs under stress conditions. In elderly cancer patients
      chemotherapy-associated neutropenia very frequently causes fever or infection
      with dose delay and increased morbidity and mortality rate, therefore in this
      setting beneficial effects of adjunct treatment with GFs have been proposed.
      Since reduction in neutropenia and in the risk of infection does not necessarily
      result in improved remission rate and long-term survival, some recommendations on
      the use (or abuse) of GFs are reviewed in this paper.

PMID- 9250013
TI  - Nutritional aspects of elderly cancer patients.
AB  - Lack of studies on the evaluation of nutritional aspects of the elderly affected
      by cancer does not allow a direct analysis of the problem. The single factors can
      be summarised in the following way: a) the aging process determines variations in
      body composition causing a reduction in organ and apparatus functionality; thus
      limiting adaptation to increased work load; b) the aging process favours the
      development of nutritional deficit in elderly subjects without cancer; c)
      nutritional support is effective in improving the clinical course of elderly
      malnourished patients affected by benign disease; d) the presence of cancer is
      frequently associated with malnutrition caused by local and systemic factors
      which depend on the tumor as well as on anti-cancer therapy; e) the frequency of
      cancer malnutrition varies with the type and stage of the tumor; f) the frequency
      and degree of malnutrition due to radiotherapy correlates with the site and size
      of the irradiated area and dose of radiation, but not with the age of the
      patient; g) artificial nutrition is effective in preventing or treating cancer
      malnutrition, can allow cycles of radiotherapy or chemotherapy to be completed or
      carried out and reduce the risk of postoperative complications in severely
      malnourished patients but does not seem to limit the toxicity of radiation or
      chemotherapy or to improve the patient's survival.

PMID- 9250014
TI  - Pain therapy in elderly cancer patients.
AB  - In most (65-80%) cancer patients at an advanced stage of illness we find
      significant, invalidating symptoms of pain. Cancer pain is a complex pain (with a
      nociceptive, neuropathic and deafferentation component), which requires a
      multidisciplinary approach (surgery, radiochemotherapy, and pain therapy). Pain
      therapy has various pharmacological strategies at its disposal (opiates, anti
      inflammatory and adjuvant drugs) together with modulation and neurodestructive
      techniques, which must be applied taking account of both the stage of the disease
      and the pain intensity. In elderly patients, a careful, tailored management of
      pharmacological therapy is required. In older age, personality disorders are also
      to be found (anxiety, depression, hypocondria and feeling of abandonment), which
      make therapy more complex and varied. Knowledge of these problems will, however,
      make it possible to control cancer pain in elderly patients to the best possible
      effect and improve the quality of life in the advanced and terminal stages.

PMID- 9250015
TI  - Radiotherapy in the elderly: a multicentric prospective study on 2060 patients
      referred to 37 Italian radiation therapy centers.
AB  - 60-70% of all cancers will develop in the year 2000 in persons aged 65 and over.
      Radiation therapy will play a major role in the treatment of cancer, especially
      in the elderly. The Italian "Geriatric Radiation Oncology Group" (GROG) performed
      in 1994 a prospective study, in order to assess the characteristics of any old
      cancer patient referred to radiation oncology centers (age, gender performance
      status, comorbidity, activities of daily living, family status) and the main
      features of the tumor in that patient. In about 6 months 2060 patients aged 70
      and over entered the study, of whom 1809 were treated with radiotherapy alone,
      with curative intent in 563 patients, in combination with surgery and/or
      chemotherapy in 476 and with palliative intent in 769 patients. Most patients had
      grade 0-1 acute toxicity.

PMID- 9250016
TI  - Radiation therapy of bone metastases in the elderly: a multicentric survey of the
      Italian "Geriatric Radiation Oncology Group".
AB  - External radiation therapy (ERT) has been reported to be the elective treatment
      of symptomatic bone metastases. A nationwide survey on the use of ERT in elderly
      patients with bone metastases has been conducted by the Italian "Geriatric
      Radiation Oncology Group" with a three-fold aim: define the state of the art of
      ERT, evaluate the analgesic efficacy and identify the optimal dosage and
      schedule, if any. 347 patients aged 70 or over, treated in 29 different
      institutions for a period of six months were analyzed. Conclusive results were: a
      significant pain relief achieved shortly after ERT completion; an improvement in
      the quality of life; a decrease in the dose of analgesics and consequently, a
      reduction in treatment-related costs. Unfortunately the optimal treatment
      schedule remains unidentified; ERT was neither aggressive nor toxic in this
      series of elderly patients.

PMID- 9250017
TI  - Radiotherapy in the elderly with lung carcinoma: the experience of the Italian
      "Geriatric Radiation Oncology Group".
AB  - One hundred ninety-six patients aged > or = 70 years, with non small-cell lung
      carcinoma and no evidence of metastasis on staging, observed over a 6-month
      period in 20 Italian Radiotherapy Centers, were analyzed in order to assess
      indications for treatment, tolerance of radiotherapy (assessed in terms of
      completion of planned doses and toxicity), and quality of life using the
      Performance Status and a concise activity of life test. Of the 196 patients
      studied in 20 Italian Centers, 182 (98%) underwent radiotherapy, 109(60%) of whom
      with radical intent and 73 (40%) with palliative intent. Of 179 assessable
      patients undergoing radiation treatment, 163 (91%) completed the treatment as
      originally planned. Of the 64 assessable patients who completed palliative
      radiotherapy, relief of symptoms was observed in a percentage ranging from 78% to
      86%. Analysis of parameters assessing the quality of life, showed no significant
      differences in general and functional conditions, as assessed before and upon
      completion of radiotherapy.

PMID- 9250018
TI  - Current controversies in the therapeutic approach to early breast cancer in the
      elderly.
AB  - Over a 7-year period, in 408 patients aged 70 years or more, 413 early breast
      cancers were treated as follows: quadrantectomy, axillary dissection, and
      radiotherapy (QUART) in 142 patients, wide lumpectomy plus radiotherapy extended
      to the axilla in case of palpable nodes (WLRT) in 45 patients and wide lumpectomy
      alone in 221 patients. Postoperative tamoxifen was given to 251 patients and
      chemotherapy to 31. Mean follow-up was 54 months. Relapse free survival was
      similar at 5 years in the three groups (80%); at 10 years it was 80.8% in QUART,
      61.3% in WLRT, 51.7% in WL. Locoregional recurrence, as first failure, occurred
      in 1.4% QUART, 6.5% WLRT and 15.2% WL. In our experience compliance with surgical
      day-hospital regimen was excellent, while postoperative radiotherapy created some
      problems, mainly among oldest patients. We support the role of radiotherapy for
      its positive impact on local control.

PMID- 9250019
TI  - In vivo cell kinetics in elderly patients affected by squamous cell carcinoma of
      the head and neck.
AB  - The purpose of the study was to determine whether pretreatment tumor cell
      kinetics can predict local control in elderly patients affected by squamous cell
      carcinoma of the head and neck (SCC-HN) and help guide different therapeutic
      modalities. Over a 6-year period, 52 patients with stage II to IV SCC-HN and aged
      more than 70 years were given an infusion of bromodeoxyuridine (BrdUrd) 6 hours
      prior to tumor biopsy sampling. The simultaneous labeling S phase fraction (LI)
      and duration (Ts) as well as potential doubling time (Tpot) were measured with
      flow cytometric analysis of BrdUrd and DNA content. Patients were then treated as
      follows: 14 with conventional radiotherapy; 13 with partly accelerated
      radiotherapy; 11 with chemoradiotherapy; 14 with surgery plus adjuvant
      radiotherapy. Univariate analysis showed that, independently of treatment type,
      patients with fast growing SCCs-HN characterized by Tpot value < or = 5 days had
      a lower three-year local control than patients with slow growing tumors with Tpot
      value > 5 days. Our results also demonstrated that surgery or chemoradiotherapy
      were effective treatments for fast growing tumors. Radiotherapy alone, instead,
      was more effective for slow growing tumors. Our data suggest that in vivo cell
      kinetics may play a role as additional prognostic factor for elderly patients
      with SCC-HN and predict the outcome of different treatments.

PMID- 9250020
TI  - Coenzyme Q10 and colorectal neoplasms in aged patients.
AB  - Coenzyme Q10 (CoQ10), a quinone located in cellular membranes, is a compound with
      mitochondrial bioenergetic functions whose antioxidant activity has recently been
      defined. CoQ10 content in colorectal neoplasms is significantly higher than in
      normal colorectal mucosa. While older patients (aged over 70 years) have also a
      significantly higher CoQ10 content, not observed in younger patients (aged under
      70 years), the normal mucosa, instead; shows constant CoQ10 levels in both
      groups. For the same local stage (T), an increase in lymph node involvement (N)
      was observed in older patients as compared to younger ones, but not in distant
      metastases (M) with the same 5-year survival. These results justify the same
      therapeutic approach for patients older or younger than 70 years.

PMID- 9250021
TI  - Radiation therapy in the elderly with head and neck cancer.
AB  - Head and neck cancer is quite common in the elderly, its most common origin being
      the larynx, oropharynx and oral cavity. In patients aged 70 and over, assessment
      of comorbidity and performance status is very important in order to establish the
      most suitable therapeutic approach, if feasible. Often radiation therapy is the
      only choice because the patient general condition may entail an excessively high
      risk for surgery. In the literature there are scarce studies focusing on
      radiation therapy and its complications, and only retrospective data are
      available: for this reason the Italian "Geriatric Radiation Oncology Group"
      (GROG) has planned a prospective study in order to collect the different results
      achieved in head and neck cancer treated in the same period with radiation
      therapy, or surgery or both.

PMID- 9250022
TI  - The explosion of structural information on insect neuropeptides.

PMID- 9250023
TI  - Sesquiterpenoids from Thapsia species and medicinal chemistry of the
      thapsigargins.

PMID- 9250024
TI  - Pregnane glycosides.

PMID- 9250026
TI  - AAON advisory. Multi-state practice.

PMID- 9250025
TI  - Understandings of health. How individual perceptions of health affect health
      promotion needs in organizations.
AB  - The purpose of the study was to discover what the concept of health means to the
      participants and to determine how an organization can assist its members in
      developing and maintaining their notion of health. The participants for this
      study were drawn from the employees at a post secondary educational institution.
      Tape recorded interviews were transcribed by the researcher, and the transcripts
      were analyzed for common topics and predominant themes. Imbedded in the data were
      four themes that provided an over arching conceptual framework from which to view
      health and health promoting activities: well being as a broad definition of
      health; the concept of balance as a prime contributor to health; the notion of
      self efficacy in determining one's health, and the value of caring as a
      significant determinant of health. Findings of the study have significance for
      individual health, organizations and health, health promoters, and further
      research.

PMID- 9250027
TI  - Business process design. Using information technology systems in the occupational
      health service business plan.

PMID- 9250028
TI  - Empowerment and occupational health nursing. A conceptual framework for reducing
      role ambiguity and facilitating client empowerment.

PMID- 9250030
TI  - Awards recognize research excellence.

PMID- 9250029
TI  - Ergonomics. A key component in a CTD control program.

PMID- 9250031
TI  - Sexual harassment: what every occupational health nurse needs to know.

PMID- 9250032
TI  - Labour force planning and policy development: issues for nursing.

PMID- 9250033
TI  - High-dependency nursing.

PMID- 9250034
TI  - Critical care management of the patient with acute respiratory distress syndrome
      (ARDS). Part 1: Pathophysiology and implications for mechanical ventilation.
AB  - Acute respiratory distress syndrome (ADRS) is a severe, life-threatening
      consequence of certain pulmonary and systemic insults. It is thought to result
      from a dramatic change in the permeability of the alveolar-capillary membrane,
      allowing the movement of fluid and proteins into alveolar air spaces. These
      changes are followed by inactivation of surfactant, bringing about a significant
      alteration in lung compliance. It is common for the devastating changes to lung
      function in ARDS to necessitate the patient being supported by mechanical
      ventilation. However, the poor compliance of the ARDS-affected lung can greatly
      increase the risk of ventilator induced lung injury. This has led to a concern
      that traditional ventilation strategies may in fact be perpetuating the very
      conditions they attempt to compensate for.

PMID- 9250036
TI  - Chest X-ray quiz. Transposition of the great vessels.

PMID- 9250035
TI  - Costing intensive care services: a review of study methods, results and
      limitations.
AB  - Critical care services are an identified, resource-intensive component of health
      care provision. Examining cost containment and clinical effectiveness in this
      specialty is therefore highly appropriate, although difficult to achieve in
      practice. The studies reviewed in this paper utilised various methodologies to
      capture different components of service and patient costs. The methods included
      combinations of per diem costs, hospital charges, direct consumption and
      unspecified cost estimates. Medical fees were commonly excluded and other costs,
      such as equipment and overheads, often not identified. Some more recent studies
      used clinical costing methods to capture individual patient-specific data, and
      demonstrated the feasibility and importance of these projects. Differing methods
      and data collection resulted in a limited comparative analysis, but issues
      requiring further research are highlighted. Funding of ICU services in Australia
      and nursing staff costs are also discussed. Future research will be aided by
      further sophistication in clinical information systems and the desire for
      clinicians to examine the link between costs and outcomes of the different
      activities pursued within the ICU.

PMID- 9250038
TI  - Heel pressure relieving devices how effective are they?
AB  - This study of patients hospitalized for hip replacement or treatment of hip
      dislocation or fractured neck or shaft of the femur compared the efficacy of
      three approaches to the care of the patients' heels. A control group of 15
      patients received routine nursing care and treatment groups of 15 and 20 patients
      received routine nursing care combined with the use of hydrocolloid dressing and
      eggcrate foam respectively. The combination of routine nursing care and the use
      of eggcrate foam was found to be more effective method of maintaining skin
      integrity than nursing care alone or nursing care combined with the use of
      hydrocolloid dressing. The study findings support the use of eggcrate foam as a
      heel pressure relieving device and it is recommended that its use is initiated
      from the time patients are admitted to hospital.

PMID- 9250039
TI  - Gestational diabetes critique.

PMID- 9250040
TI  - Interview with: Margaret Charles Smith. Interview by Ina May Gaskin.

PMID- 9250041
TI  - Granny-midwives: matriarchs of birth in the African-American community 1600-1940.

PMID- 9250042
TI  - Interview with Sister Evelyn CNM. Interview by Kim Ploch.

PMID- 9250043
TI  - Oxytocin: key hormone in sexual intercourse, parturition, and lactation.

PMID- 9250044
TI  - Making a difference: yoga in pregnancy!

PMID- 9250045
TI  - The marketing of elective breast surgery.

PMID- 9250046
TI  - The Coalition for Improving Maternity Services.

PMID- 9250047
TI  - More on infant colic.

PMID- 9250048
TI  - The letter the Washington Post didn't print: home birthing--and living.

PMID- 9250049
TI  - Interview: Beatrijs Smulders. Interview by Ina May Gaskin.
AB  - The Netherlands' stubborn refusal to march in lock-step with the rest of the
      industrialized world, when it comes to maternity care provides important lessons
      for other nations. Beatrijs Smulders, author of Baren ('Giving Birth') and
      producer of several videos on vertical home-birthing, has been working as an
      Amsterdam midwife since 1979 and today plays a leading role in Dutch midwifery.
      Here, she explores new territory through home birth, working toward a practice
      both less regulated by and less reliant on prevailing institutions.

PMID- 9250050
TI  - Interview with Elizabeth Gilmore. Interview by Ina May Gaskin.

PMID- 9250051
TI  - The disappearance of birth: language versus reality in modern childbirth.

PMID- 9250052
TI  - Medication during childbirth.

PMID- 9250053
TI  - The art of nurturing: a primary skill of mothers and midwives.

PMID- 9250054
TI  - The special gift: breastfeeding your adopted baby.

PMID- 9250055
TI  - Update on obstetric drugs and procedures: their effects on maternal and infant
      outcome.

PMID- 9250056
TI  - What's wrong with standards?

PMID- 9250058
TI  - Needed change in maternity care options in the United States.

PMID- 9250057
TI  - Free-will and epidurals: does today's mother have a choice?

PMID- 9250059
TI  - Abby Kinne CPM. Interview by Ina May Gaskin.

PMID- 9250060
TI  - Interview with Ihsan Fahri, MD. Interview by Ina May Gaskin.

PMID- 9250061
TI  - Interview with JoAnne Myers-Ciecko. Interview by Ina May Gaskin.

PMID- 9250062
TI  - Who is a midwife? Or, is exclusivity or inclusivity our strength?

PMID- 9250063
TI  - Giving peace a push. Interview by Judith Gips.
AB  - Lifelong peace and justice activists Dave Dellinger and Elizabeth Peterson have
      been inspirations to many, including myself, over the last fifty or more years.
      Dave's collection of essays, Revolutionary Nonviolence, spanning thirty years of
      committed and loving resistance to injustice in all its forms, is an illuminating
      glimpse into how things could be if more of us shared such willingness to examine
      our assumptions and our privileges. Here they tell us of birthing their five
      children, three at home. They have eleven grandchildren and two great
      grandchildren.

PMID- 9250064
TI  - The importance of core values in nursing.

PMID- 9250065
TI  - Relatives' views of care in residential/nursing homes.

PMID- 9250066
TI  - Nurses' documentation of infection control precautions: 1.
AB  - Inadequate nursing records may contribute to untoward incidents and yet advised
      precautions for the control of infection can be poorly documented. The infection
      control nurse must promote a safe environment for the patient and ensure that an
      effective control policy is carried out. The literature suggests that nurses may
      lack the necessary knowledge and skills with which to assess, plan and evaluate
      appropriate care for safe infection control. This article, the first of two
      parts, discusses these issues together with various strategies at the infection
      control nurse's disposal that may influence nursing practice and the
      documentation of care.

PMID- 9250067
TI  - Preventing complications in people who wear contact lenses.
AB  - The number of contact lens wearers has steadily increased over the past 10 years.
      Convenience, efficiency and availability of different types of lenses have made
      them popular. The rise in the use of contact lenses has increased the number of
      people at risk of contact lens-related complications. Studies have highlighted
      the consequences of poor contact lens care. Acanthamoeba keratitis is one of the
      most devastating complications of contact lens wear and can be avoided by
      adhering to the recommended contact lens regimen. This article reviews the
      literature on the complications of contact lens wear and stresses the need to
      educate the wearer. It examines the nurse's role in relation to health promotion
      and the basic principles for successful long-term contact lens wear. This
      information is relevant to all nurses caring for people with contact lenses and
      will be of particular interest to the nurse who wears contact lenses.

PMID- 9250068
TI  - Medical investigations. 5: colonoscopy.

PMID- 9250069
TI  - Evaluation of a paediatric diabetes specialist nurse post.
AB  - The specialist nurse caring for children with diabetes is widely recognized as a
      valued member of the paediatric diabetes team. However, there has been minimal
      exploration or examination of the clinical role of the paediatric diabetes
      specialist nurse (PDSN). This in-depth evaluation critically examines the impact
      of a PDSN post, comparing data from the first 2 years of the post against
      corresponding data from the previous 2 years. Results are encouraging, showing
      that much has been achieved. Home management was successfully introduced, length
      of stay was halved for newly diagnosed children initially hospitalized, suggested
      guidelines for length of stay for readmissions were met, age-banded education
      sessions were implemented and clinic non-attendance was substantially reduced.
      The readmission rate for children with established diabetes was increased, and
      reasons for this are discussed outlining intervention being introduced to
      proactively address this problem. The findings from this evaluation support the
      belief that PDSNs, as members of a multidisciplinary team, make a substantial and
      valuable contribution to paediatric diabetes care.

PMID- 9250070
TI  - Flexible roles: a new model in nursing practice.
AB  - The problem of how to retain experienced nurses within a given specialist field
      impacts on both nurses and managers. This article explores the development of a
      new clinical role which gives experienced E and F grade nurses the opportunity
      for personal and professional growth. Within the new role, 50% of the nurse's
      time is devoted to ward-based clinical work and the other 50% to developing an
      area of clinical practice or research, as is the case with some clinical nurse
      specialists. There is flexibility over the area of specialist interest to reflect
      the needs of the service and the expertise and interests of the individual, and
      there is also flexibility in relation to the clinical commitment which increases
      opportunities for job shares. This development has arisen from an organizational
      culture which recognizes the need for more flexible job classifications and work
      rules. This new model for practice also represents a new model for management. In
      fostering self-reliance within the workforce it enables all parties to work
      towards a shared vision which is mutually beneficial for nurses, managers, the
      organization and, most importantly, the patient.

PMID- 9250071
TI  - Clinical guidelines: legal and clinical risk management issues.
AB  - Clinical guidelines are becoming a frequent feature of the care environment. With
      more patients resorting to litigation and complaints the legal aspects of
      guidelines takes on an increasing significance. Cases on clinical guidelines have
      gone to court. This article discusses examples of these and gives practical
      guidance on some key legal aspects of clinical guidelines such as the need to
      schedule a review date and to fully document the development process. Dangers of
      clinical guidelines are also highlighted. The author further develops some of the
      themes on legal and clinical risk management aspects of guidelines that he
      discussed in a previous article (Vol 5(5): 266-7).

PMID- 9250072
TI  - A review of nurse occupational stress research: 1.
AB  - This is the first in a series of articles that review the field of nurse
      occupational stress research. The review in its entirety provides a focus for
      further research on nurse stress; further research is crucial, especially at a
      time when major changes in nursing and the NHS in general provide major
      challenges which some people would argue are critical prerequisites for increased
      work-related stress. The review highlights the many weaknesses and gaps in nurse
      stress research and invites future researchers to take up the challenge.

PMID- 9250073
TI  - The ethical dilemma of the do not resuscitate order.
AB  - Tingle (1988) stated that doctors and nurses frequently find themselves in the
      position of making decisions which are not solely medical or nursing but of a
      moral or ethical nature. To illustrate this concept the author describes and
      analyses how the ethical arena has impinged upon her practice. Professional
      accountability and patient involvement are critical issues which need to be
      addressed. Do not resuscitate decisions should be based on a collaborative
      approach centred around the patient.

PMID- 9250074
TI  - Compulsory removal of competent adults from their homes.
AB  - The National Assistance Act 1948 was enacted in order to provide the legal
      framework for the care and support of society's ill and socially deprived. In
      certain limited circumstances, Section 47 of this Act permits the compulsory
      admission of competent adults to hospital or to other types of residential care.
      The fine balance between protection from harm and respect for personal freedom is
      not served well by this Act which has its origins in Poor Law legislation. It is
      no longer in accordance with current practice and therefore needs to be reviewed.
      This could be achieved by setting up regulatory systems to protect the rights of
      individuals considered to be in need of compulsory admission. However, it seems
      likely that the only way to protect the individual's civil liberties effectively
      is by changing the existing law.

PMID- 9250075
TI  - Whistleblowing guidelines for nursing colleagues.

PMID- 9250076
TI  - Hormone replacement therapy and breast cancer risk.

PMID- 9250077
TI  - Breast cancer detection by daughters of women with breast cancer.
AB  - PURPOSE: This study was conducted to determine the frequency of breast self
      examination (BSE), clinical breast examination, and mammography of adult
      daughters of women with breast cancer. Additionally, the relationships among
      frequency of self-examination, clinical examination, perceived risk, fear of
      breast cancer, and frequency of talking with their mothers about breast cancer
      were assessed. METHODS: A retrospective, correlational descriptive design was
      used. Questionnaires were mailed to members of a breast cancer support group and
      to women diagnosed with breast cancer in one medical oncology practice. These
      women were asked to mail the questionnaires to their adult daughters. RESULTS:
      There was a significant relationship between frequency of BSE and frequency of
      talking with mothers about breast cancer. Frequency of self-examination was
      related inversely to fear of breast cancer. Fear of breast cancer appears to act
      as a barrier to action whereas frequency of talking with their mothers about
      breast cancer seems to act as a cue to action in support of the Health Belief
      Model. CLINICAL IMPLICATIONS: Healthcare providers should make every effort to
      optimize the practice of BSE in daughters of women with breast cancer. Only 52%
      reported performing BSE monthly, with the remaining 48% performing BSE less
      frequently or not at all. Thirty-one percent reported having no formal or printed
      instruction regarding BSE. Health professionals caring for women who have a
      family history of breast cancer should assess the educational needs of these
      women and provide opportunities for them to acquire and demonstrate skills.
      Periodic re-evaluation of BSE is needed to reinforce importance and demonstrate
      technique. The development of educational materials developed specifically for
      daughters of women with breast cancer may be useful in diminishing the perception
      of an unrealistically high risk of developing breast cancer. With the decrease in
      fear, which appears to be acting as a barrier to BSE in this group, better breast
      cancer detection practices in daughters may be realized. Counseling about
      realistic risk of developing breast cancer also may be useful in reducing the
      amount of fear of breast cancer in these women. This is an unnecessary burden for
      any woman to bear and may interfere with her optimal practice of breast cancer
      detection practices.

PMID- 9250078
TI  - Helpseeking for self-discovered breast symptoms. Implications for early
      detection.
AB  - PURPOSE: Most breast cancer symptoms are discovered by women themselves, and at
      least one third of these women will be aware of their symptoms for 3 months or
      more before seeking an initial provider evaluation. The authors identify
      personal, social, and environmental influences on women's intention to seek an
      immediate provider evaluation (helpseek) versus to delay evaluation of a breast
      symptom that worried them. DESCRIPTION OF STUDY: Black women (N = 352) from the
      San Francisco Bay are women's organizations, community settings, and churches
      formed this convenience sample. Participants ranged across age, income, and
      educational levels. The survey contained 10 scales that measured health behavior
      variables, including new and existing scales augmented by items derived from
      prior interview and focus group investigations. RESULTS: Women of younger age and
      lower income were significantly less likely to intend to seek an evaluation for
      self-discovered breast symptoms. Single and partnered women were less likely to
      seek a provider evaluation than married or widowed women. Perceiving negative
      consequences of delaying, having previous habits of healthcare utilization,
      perceiving access to services, and feeling fearful were positively related to the
      intention to seek evaluation of breast symptoms. Holding fatalistic beliefs about
      getting breast cancer or dying and perceiving constraints to seeing a provider
      negatively influenced helpseeking intention. Racism in the healthcare delivery
      system was perceived, but was not a significant influence on helpseeking
      intention. A multiple linear regression model containing these variables
      explained 46% of the variance in helpseeking intention. CLINICAL IMPLICATIONS:
      This study shows that the intent to helpseek is not merely a matter of education
      and economics, but is dependent on a complex picture of personal, social, and
      economic factors. Gynecologic and primary care providers should consider this and
      the potential influences on helpseeking in the women for whom they provide cancer
      screening and early detection services. History taking should be expanded to
      assess women's ideas about the consequences of delaying evaluation of self
      discovered breast symptoms, their sense of vulnerability to breast cancer, the
      constraints on cancer early detection they may be feeling related to role
      obligations, their economic or strategic limitations to accessing services, the
      pressures they may feel to hide a breast cancer symptom, or their own tendency to
      interpret the breast symptom as not threatening. Healthcare providers should not
      assume that helpseeking for breast symptoms is an automatic behavior for all
      women. Rather, providers should assess whether a women is the one in three who
      will delay the evaluation of a breast cancer symptom she discovers herself for
      months or years.

PMID- 9250079
TI  - Establishing a cancer risk evaluation program.
AB  - PURPOSE: Presymptomatic genetic testing for cancer susceptibility is a new
      practice arena that raises many complex issues. This article presents one model
      of a cancer risk evaluation program that specifically addresses the unique issues
      associated with genetic testing for cancer risk. DESCRIPTION OF PROGRAM: The
      Cancer Risk Evaluation Program is designed to care for any individual concerned
      about his or her risk for cancer, offering predisposition genetic testing if
      appropriate. The program includes clinical and psychosocial assessment,
      education, cancer risk analysis, and genetic counseling; it offers long-term
      screening and surveillance and provides a forum for ongoing genetic and clinical
      research. RESULTS: Program evaluations from participants have shown that the
      program is successfully meeting the needs of the participants. This program also
      ensures that the University of Pennsylvania Cancer Center is delivering cancer
      genetic services consistent with the existing position statements on genetic
      testing for cancer susceptibility, which have included guidelines and indications
      for predisposition genetic testing and informed consent. CLINICAL IMPLICATIONS:
      Researchers anticipate a substantial demand for predisposition genetic testing
      for cancer susceptibility. However, not all individuals interested in testing are
      eligible or willing to undergo direct gene analysis because of the potential
      risks. Therefore, clinical programs must address the complex issues surrounding
      presymptomatic genetic testing and incorporate cancer risk assessment strategies.
      Additionally, healthcare providers in this new practice arena should be fully
      informed and current in the state of the knowledge regarding cancer risk
      assessment; predisposition genetic testing; and the ethical, legal, and social
      issues pertaining to cancer risk assessment and management.

PMID- 9250080
TI  - Proactive psychosocial care of blood or marrow transplant patients.
AB  - PURPOSE: The authors describe a proactive model of psychosocial care for patients
      undergoing blood or marrow transplantation and their families. DESCRIPTION OF
      PROGRAM: This program for blood or marrow transplantation patients, developed at
      the Center for Cancer Treatment and Research, Richland Memorial Hospital, and the
      University of South Carolina School of Medicine in Columbia, South Carolina,
      involves pretransplant comprehensive psychosocial assessment; development and
      implementation of an individual psychosocial treatment plan; monitoring and
      medical management of neuropsychiatric problems; and psychotherapeutic sessions
      with a psychiatrist. These functions are achieved through the use of a
      multidisciplinary psychosocial team and ongoing consultation-liaison with the
      entire blood or marrow transplantation team. CLINICAL IMPLICATIONS: This
      positive, proactive model demonstrates significant benefit to patients, families,
      and the blood or marrow transplantation healthcare team. Benefits of this model
      are derived from psychosocial assessment during work-up, subsequent planning, and
      communication with the entire team, thus allowing early identification of
      problems and avoiding escalation and the likelihood of negative outcomes. Less
      energy is exerted and less resources expended when problems are resolved with
      early intervention rather than with intensive interventions during transplant.
      The psychosocial staff members develop strong relationships with patients and
      families before transplant, increasing the power of interventions and receptivity
      of the patient. The blood or marrow transplantation team benefits from the
      ongoing presence of psychosocial staff and the consistency of approaches offered
      by team members. An integral part of this approach is teaching psychosocial care
      to all staff members and modeling approaches to problems. Other blood or marrow
      transplantation centers and centers providing other intensive anticancer
      therapies may benefit by adapting this model into the day-to-day care of their
      patients.

PMID- 9250081
TI  - The role of informal and formal social support networks for patients with cancer.
AB  - PURPOSE: In this study, the authors examined the role of informal and formal
      social support networks in mitigating barriers to cancer treatment among whites,
      blacks, and Hispanics, based on a representative sample of cancer patients in
      Texas. DESCRIPTION OF STUDY: The sample frame for this study was obtained from
      the University of Texas M. D. Anderson Cancer Center's Texas Community Oncology
      Network, a consortium of cancer treatment facilities in Texas. Of the 910
      patients who were contacted, 593 (65%) responded to the survey. RESULTS: The
      results show the value of social support networks in assisting cancer patients
      with continuing treatment. An important finding indicated that health
      professionals do not provide information regarding social support groups to
      patients with cancer at the time of diagnosis. Fewer than half of the respondents
      were asked whether they would be interested in joining a formal social support
      group. Individuals of all racial/ethnic groups reported that the formal support
      groups provided emotional assistance. Minorities were more apt to report that the
      formal support groups helped with continuing treatment. In addition, informal
      social support networks, such as extended families and civic clubs, were seen as
      more helpful for blacks and Hispanics as compared with whites. CLINICAL
      IMPLICATIONS: The need for formal and informal networks is indicated by the
      results of this study, which show that networks, such as relationships with
      family, friends, and relatives, play an important role in assisting patients in
      coping with their cancer. These networks are part of the patient's total
      treatment experience and must be acknowledged by healthcare professionals. A
      large number of patients are not asked to join social support groups, suggesting
      a need for training healthcare professionals to provide information regarding the
      potential benefits of support groups for cancer patients.

PMID- 9250082
TI  - An ovarian cancer support group.
AB  - PURPOSE: Because of the low rate of cure and high rate of relapse, the disease
      course of ovarian cancer can be emotionally devastating. Using psychological
      interventions to support patients emotionally and to enhance their quality of
      life should therefore be considered an important complement to medical care.
      OVERVIEW: The authors describe a support group for patients with ovarian cancer,
      which was conducted over a 2-year period. The group consisted of patients with
      poor prognoses whose experience ranged from initial medical treatment, remission,
      and relapse to the dying experience. Key themes that arose during the sessions
      are identified, and differences between psychotherapy groups and support groups
      are highlighted. In contrast to psychotherapy groups, existential issues stood
      out as the most important therapeutic factor in this support group. CLINICAL
      IMPLICATIONS: Because it is widely acknowledged that support groups have unique
      value in the total care of women with ovarian cancer, this description of issues
      related to group process hopefully will assist others who may plan to offer this
      type of psychological intervention for patients. With increasing technology and
      the resulting extension of life for patients with ovarian cancer, support groups
      like this may become an important aspect of care to enhance quality of life. The
      multidisciplinary team, including psychiatry, social work, nursing, and
      chaplaincy, is essential in expanding support groups in healthcare settings.

PMID- 9250083
TI  - The end of the continuum. Bereavement care for the adult.

PMID- 9250084
TI  - The cancer survivor as co-investigator. The benefits of collaborative research
      with advocacy groups.

PMID- 9250085
TI  - Management of hormone-sensitive metastatic prostate cancer. Update on hormonal
      therapy.

PMID- 9250086
TI  - NAHN conference highlights Hispanics as the "emerging majority".

PMID- 9250087
TI  - Accreditation Committee completes 1996 Core Criteria.

PMID- 9250088
TI  - NLN development series targets community-based education.

PMID- 9250089
TI  - Self-study modules help health care professionals recognize and prevent abuse.

PMID- 9250090
TI  - "Everyone is part of the community": Romaine Martin Semeah on CHAP. Interview by
      Kelly Jo Woodside.

PMID- 9250091
TI  - NLN board votes to establish independent accrediting commission.

PMID- 9250092
TI  - Collaboration among communities. NLN's new Center for Collaborating Organizations
      and Community Groups introduces exciting plan for health care futures.

PMID- 9250093
TI  - Tapestry of tears.

PMID- 9250094
TI  - "Redesigning systems for cost-effective quality health care" sets a precedent for
      NLN councils.

PMID- 9250095
TI  - Second Annual Research Institute explores health needs of diverse populations.

PMID- 9250096
TI  - Key issues facing nursing education: report of survey at the Council of
      Baccalaureate and Higher Degree Programs annual meeting.

PMID- 9250097
TI  - Center for Human Caring certificate program receives high praise from
      participants.

PMID- 9250098
TI  - Fitness, fatness, and the effect of training assessed by magnetic resonance
      imaging and skinfold-thickness measurements in healthy adolescent females.
AB  - The relation between fitness and adiposity is particularly relevant to adolescent
      females in whom fitness is known to decrease and fatness to increase. However,
      little is known about the interaction of these variables in normally active,
      nonobese subjects. Our major hypotheses were that adiposity would be inversely
      correlated with physical fitness and that even a relatively brief intervention
      would lead to measurable, site-specific changes in body fat. We used a cross
      sectional protocol to correlate body adiposity with indexes of fitness and a
      prospective study design to examine body adiposity before and after a 5-wk period
      of endurance training in 44 nonobese females aged 15-17 y (control group, n = 22;
      training group, n = 22). Adiposity was assessed by magnetic resonance imaging of
      the abdomen and thigh as well as by standard skinfold-thickness measuring
      techniques. Fitness was assessed by using cycle ergometer measurements of maximal
      oxygen uptake (VO2max). There were significant negative correlations between
      VO2max normalized to body weight and subcutaneous abdominal, thigh, and skinfold
      estimates of fat. However, when VO2 max was normalized to muscle volume these
      correlations were not significant. Abdominal fat increased in direct proportion
      to body weight (scaling factor = 1.14 +/- 0.16) but thigh fat increased
      proportionately less (scaling factor = 0.38 +/- 0.12, P < 0.05). Training
      increased thigh muscle mass significantly only in the midmuscle region and
      prevented the observed fat increase in the distal thigh of the control subjects.
      Body fat distribution in adolescent females appeared to be affected by many
      factors, including overall body weight and the level of physical activity.

PMID- 9250099
TI  - Determinants of body composition measured by dual-energy X-ray absorptiometry in
      Dutch children and adolescents.
AB  - Knowledge about body composition is important in metabolic and nutritional
      studies. In this cross-sectional study the body composition of 403 healthy white
      Dutch children and adolescents was evaluated by using dual-energy X-ray
      absorptiometry (DXA). Possible determinants of body composition were analyzed. In
      85 subjects the results of bioelectrical impedance analysis (BIA) were compared
      with DXA. Fat mass, lean tissue mass, and bone mineral content were greater in
      older boys and girls. Percentage body fat was greater in older girls but not in
      boys and it was higher in girls than in boys at all ages. From the age of 14 y
      boys had higher lean tissue mass and bone mineral content than girls. Tanner
      stage had a significant relation with body composition in both sexes. Percentage
      body fat was lower in boys in stage 4 than in stage 3 and was higher in
      consecutive Tanner stages in girls. After adjustment for age, Tanner stage was
      significantly positively related to lean tissue mass and bone mineral content in
      boys and girls and to percentage body fat and fat mass in girls. The profession
      of the parents and the education of the father had a significant negative
      correlation with percentage body fat and fat mass in girls (P < 0.01). Physical
      activity was related to lean tissue mass (P = 0.001) but not to fat mass in boys
      after adjustment for age. A high correlation and a small difference was found
      between lean body mass by BIA and lean tissue mass by DXA. Body composition in
      healthy Dutch children and adolescents is related to age, sex, Tanner stage,
      socioeconomic status, and physical activity.

PMID- 9250100
TI  - A descriptive study of individuals successful at long-term maintenance of
      substantial weight loss.
AB  - The National Weight Control Registry (NWCR) is, to the best of our knowledge, the
      largest study of individuals successful at long-term maintenance of weight loss.
      Despite extensive histories of overweight, the 629 women and 155 men in the
      registry lost an average of 30 kg and maintained a required minimum weight loss
      of 13.6 kg for 5 y. A little over one-half of the sample lost weight through
      formal programs; the remainder lost weight on their own. Both groups reported
      having used both diet and exercise to lose weight and nearly 77% of the sample
      reported that a triggering event had preceded their successful weight loss. Mean
      (+/-SD) current consumption reported by registry members was 5778 +/- 2200 kJ/d,
      with 24 +/- 9% of energy from fat, Members also appear to be highly active: they
      reported expending approximately 11830 kJ/wk through physical activity.
      Surprisingly, 42% of the sample reported that maintaining their weight loss was
      less difficult than losing weight. Nearly all registry members indicated that
      weight loss led to improvements in their level of energy, physical mobility,
      general mood, self-confidence, and physical health. In summary, the NWCR
      identified a large sample of individuals who were highly successful at
      maintaining weight loss. Future prospective studies will determine variables that
      predict continued maintenance of weight loss.

PMID- 9250101
TI  - Effects of early childhood supplementation with and without stimulation on later
      development in stunted Jamaican children.
AB  - It is not known whether nutritional supplementation in early childhood has long
      term benefits on stunted children's mental development. We followed up 127 7-8-y
      old children who had been stunted in early childhood and received
      supplementation, stimulation, or both. At 9-24 mo of age, the children had been
      randomly assigned to four treatment groups: nutritional supplementation,
      stimulation, both treatments, and control. After 2 y, supplementation and
      stimulation had independent benefits on the children's development and the
      effects were additive. The group receiving both treatments caught up to a matched
      group of 32 nonstunted children. Four years after the end of the 2-y intervention
      97% of the children were given a battery of cognitive function, school
      achievement, and fine motor tests. An additional 52 nonstunted children were
      included. Factor analyses of the test scores produced three factors: general
      cognitive, perceptual-motor, and memory. One, the perceptual-motor factor, showed
      a significant benefit from stimulation, and supplementation benefited only those
      children whose mothers had higher verbal intelligence quotients. However, each
      intervention group had higher scores than the control subjects on more tests than
      would be expected by chance (supplemented and both groups on 14 of 15 tests, P =
      0.002; stimulated group in 13 of 15 tests, P = 0.01), suggesting a very small
      global benefit. There was no longer an additive effect of combined treatments at
      the end of the intervention. The stunted control group had significantly lower
      scores than the nonstunted children on most tests. Stunted children's heights and
      head circumferences on enrollment significantly predicted intelligence quotient
      at follow-up.

PMID- 9250102
TI  - Influence of n-3 fatty acid supplementation on the endogenous activities of
      plasma lipases.
AB  - The aim of these studies was to explore the possibility that enhanced
      triacylglycerol clearance may contribute to the hypotriacylglycerolemic effect of
      n-3 fatty acids in humans. Healthy subjects (n = 20) and hypertriacylglycerolemic
      patients (n = 6) were given a placebo (olive oil, OO) or a fish-oil concentrate
      (FOC; 41% eicosapentaenoic acid and 23% docosahexaenoic acid) in two,
      independent, randomized, blind trials. For the healthy subjects, the FOC
      treatment period was 3 wk long and FOC intakes were 5 g/d. For the patients,
      treatment periods were 4 wk long and dosages were 5 g.70 kg body wt-1.d-1.
      Washout periods were 2-4 wk for both groups. Blood samples were drawn at the end
      of each phase and analyzed for plasma lipids, lipoproteins, and endogenous
      (nonheparin-stimulated) activities of lipoprotein lipase (LPL) and hepatic lipase
      (HL). In the healthy subjects the FOC decreased plasma triacylglycerol
      concentrations by 18% (P < 0.01), whereas in the patients concentrations were
      reduced by 35% (P < 0.05). Low-density-lipoprotein-cholesterol concentrations
      increased by 25% in the latter group (P = 0.06). FOC increased the endogenous
      activities of LPL and HL by 62% and 68%, respectively (P < 0.0001), in the
      healthy subjects, but only LPL in the patients (65%, P < 0.005). These data
      suggest that endogenous lipase activities may be altered by nutritional
      interventions, and further, that accelerated lipolysis could contribute, at least
      in part, to the observed effects of n-3 fatty acids on human lipoprotein
      metabolism.

PMID- 9250103
TI  - Effect of tea flavonoid supplementation on the susceptibility of low-density
      lipoprotein to oxidative modification.
AB  - Dietary flavonoid intake has been reported to be inversely associated with the
      incidence of coronary artery disease. To clarify the possible role of tea
      flavonoids in the prevention of atherosclerosis, we investigated the effects of
      tea flavonoids on the susceptibility of low-density lipoprotein (LDL) to
      oxidative modification. In an in vitro study, catechins or theaflavins (25-400
      mumol/L) were added to plasma and incubated for 3 h at 37 degrees C. Then, the
      LDL fraction was separated by ultracentrifugation. The oxidizability of LDL was
      estimated by measuring conjugated diene, thiobarbituric acid-reactive substances
      (TBARS), and lipid peroxides after cupric sulfate was added. TBARS and lipid
      peroxides in the supernates were also measured after incubation with macrophages.
      Catechins significantly (P < 0.01 by ANOVA) and dose-dependently prolonged the
      lag time before initiation of oxidation. Among the catechins, epigallocatechin
      gallate exerted the most marked effect, prolonging the oxidation lag time more
      than vitamin E at the same molar concentration. Theaflavins exerted stronger
      inhibitory effects than catechins. Macrophage-mediated LDL oxidation was also
      inhibited by adding these tea flavonoids to the plasma samples. In an in vivo
      study, 14 healthy volunteers consumed 750 mL black tea/d for 4 wk. After the
      subjects had consumed tea for 4 wk, the lag time before LDL oxidation was
      significantly (P < 0.01) prolonged from 54 to 62 min. This minor prolongation
      occurred despite much lower plasma flavonoids than were used in vitro. No
      significant change was observed in eight control volunteers. LDL exposed to tea
      flavonoids in vitro or in vivo reduced oxidizability. We speculate that tea
      flavonoids may have a role in ameliorating atherosclerosis.

PMID- 9250104
TI  - Licorice extract and its major polyphenol glabridin protect low-density
      lipoprotein against lipid peroxidation: in vitro and ex vivo studies in humans
      and in atherosclerotic apolipoprotein E-deficient mice.
AB  - Polyphenolic flavonoids are powerful antioxidants. In the present study we
      investigated the antioxidative activity against low-density-lipoprotein (LDL)
      oxidation of a not yet studied subclass of polyphenols, the isoflavans, which are
      present in licorice alcoholic extract. The study was performed in humans as well
      as in atherosclerotic apolipoprotein E-deficient mice (E zero), because their LDL
      is highly susceptible to oxidation. LDL oxidation was induced by incubating it
      with copper ions as well as with the aqueous or lipid-soluble free radical
      generators 2,2'-azobis'2-amidino propane hydrochloride (AAPH) and 2,2'-azobis 2,4
      dimethylvaleronitrile (AMVN), respectively. The extent of LDL oxidation was
      determined by measuring the formation of conjugated dienes, thiobarbituric acid
      reactive-substances (TBARS), and lipid peroxides. By all methods in human
      studies, licorice ethanolic extract as well as a pure material, which was
      identified by gas chromatography-mass spectroscopy as the isoflavan glabridin,
      were shown to inhibit LDL oxidation by a mechanism involving scavenging of free
      radicals. In an ex vivo study, LDL isolated from the plasma of 10 normolipidemic
      subjects who were orally supplemented for 2 wk with 100 mg licorice/d was more
      resistant to oxidation than was LDL isolated before licorice supplementation.
      Dietary supplementation of each E zero mouse with licorice (200 micrograms/d) or
      pure glabridin (20 micrograms/d) for 6 wk resulted in a substantial reduction in
      the susceptibility of their LDL to oxidation along with a reduction in the
      atherosclerotic lesion area. These results could be related to the absorption and
      binding of glabridin to the LDL particle and subsequent protection of the LDL
      from oxidation by multiple modes as shown in humans and in E zero mice.

PMID- 9250105
TI  - Changes in fat oxidation in response to a high-fat diet.
AB  - Intervention studies have shown that the adaptation of fat oxidation to fat
      intake, when the dietary fat content is changed, is not abrupt. This study was
      conducted to measure the time course of adaptation of oxidation rates to
      increases in the fat content of the diet while subjects were fed at energy
      balance. Twelve healthy, nonobese males and females [age: 26 +/- 2 y, body mass
      index (in kg/m2): 21.4 +/- 0.5; and habitual fat intake: 29 +/- 1% of energy]
      consumed a low-fat diet for 6 d (days 1-6) followed by a high-fat diet for 7 d
      (days 7-13). Days 5-9 and 13 were spent in a respiration chamber. After
      adjustment for energy intake to 24-h energy expenditure on day 5, subjects were
      in energy balance (range: -0.15 to 0.23 kJ/d) on days 6-9 and 13. Fat balance was
      zero on day 6 but became positive after subjects changed to the high-fat diet
      (1.06 +/- 0.15, 0.75 +/- 0.15, and 0.55 +/- 0.14 MJ/d for days 7, 8, and 9,
      respectively, P < 0.05), reaching a new balance on day 13, 7 d afterward. In
      conclusion, when in energy balance, lean subjects are capable of adjusting fat
      oxidation to fat intake within 7 d of when dietary fat content is increased.

PMID- 9250106
TI  - Effect of cystine intake on methionine kinetics and oxidation determined with
      oral tracers of methionine and cysteine in healthy adults.
AB  - There is evidence based on nitrogen balance that dietary cystine spares, from
      approximately 16% to 89%, the total methionine requirement. In a previous study
      we did not detect, by tracer techniques, a sparing effect of cystine when the
      diet provided methionine at a limiting intake (requirement level: 13 mg.kg-1.d
      1). One reason could be that we used an intravenous infusion of the tracer, which
      may not, therefore, have labeled the carbon dioxide derived from the splanchnic
      oxidation of dietary methionine. The aim of this study was to compare methionine
      metabolism and oxidation in eight healthy adults given for 6 d each of three
      different diets: 13 mg (87.0 mumol) methionine.kg-1.d-1 and no cystine (diet A);
      5 mg (33.5 mumol) methionine.kg-1.d-1 and no cystine (diet B); and 5 mg (33.5
      mumol) methionine.kg-1.d-1 and 6.5 mg (52.4 mumol) cystine.kg-1.d-1 (diet C). On
      day 7, tracers ([1-13C, methyl-2H3]methionine and [2H2]cysteine) were
      administered orally at 30-min intervals for 8 h. Blood and breath samples were
      obtained for analysis during 3-h fasting and consecutive 5-h feeding periods.
      During fasting, methionine oxidation and methionine methyl (Qm) and carboxyl (Qc)
      fluxes and plasma concentrations were not affected by the amount of sulfur amino
      acids in the three diets. In the fed state methionine oxidation was significantly
      lower during diets B (3.0 +/- 0.5 mumol.kg-1.h-1) and C (2.8 +/- 0.6 mumol.kg-1.h
      1) than during diet A (4.1 +/- 0.9 mumol.kg-1.h-1); there were no significant
      differences between diets B and C. Qm and Qc decreased with decreased methionine
      intake but no effect was observed by adding cystine. Cysteine flux (Qcys) was not
      affected by diet composition but it was lower during feeding than during fasting.
      In conclusion, replacing approximately 60% of the total requirement for
      methionine with cystine over a short diet period did not result in a detectable
      sparing of methionine oxidation.

PMID- 9250107
TI  - Effect of hypoenergetic feeding and high-carbohydrate refeeding on muscle tetanic
      tension, relaxation rate, and fatigue in slow- and fast-twitch muscles in rats.
AB  - Studies using nuclear magnetic resonance have shown that undernutrition affects
      muscle performance and energetics. It is unclear to what extent underfeeding and
      refeeding influence the availability of muscle glycogen, net glycogenolysis,
      skeletal muscle wasting, and recovery. We hypothesized that muscle performance is
      independent of muscle size and weight, is specific to muscle type, and is
      unrelated to muscle glycogen concentrations. Slow- and fast-twitch muscles were
      studied in three groups of adult male Wistar rats: well-fed controls,
      hypoenergetically fed (Hypo) rats, and rats refed for 4 d after the hypoenergetic
      diet. Glycogen concentrations and net glycogenolysis; serum glucose, insulin, and
      protein concentrations; and muscle weight, protein, and cross-sectional area were
      studied relative to the performance of both types of muscles. Our study
      controlled for muscle size, weight, and type and electrolyte-micronutrient
      deficiency. Undernutrition affected muscle performance in five ways. First,
      compared with controls, fatigue increased only in the soleus muscles of Hypo rats
      yet the maximal relaxation rate (MRR) decreased in both the soleus and extensor
      digitorum longus (EDL) muscles. Second, muscle glycogen concentrations did not
      significantly correlate with fatigue in either the soleus or the EDL although net
      glycogenolysis was significantly correlated with fatigue in the soleus (r = 
      0.64; P > 0.01 < 0.05). Third, lower glycogen concentrations did not hinder net
      glycogenolysis in the EDL of Hypo rats or the soleus of refed rats. Fourth,
      muscle weight, size, and protein were dissociated from function. Fifth, refeeding
      did not restore muscle endurance; however, the MRR of the soleus normalized. In
      conclusion, glycogen values and muscle performance did not correlate but net
      glycogenolysis correlated with fatigue in the soleus. Also, there was a
      dissociation between muscle weight, size, and protein and muscle function during
      hypoenergetic feeding and refeeding.

PMID- 9250108
TI  - Acetylation of or beta-cyclodextrin addition to potato beneficial effect on
      glucose metabolism and appetite sensations.
AB  - Functional foods are gaining more and more interest from health scientists. One
      way to improve the nutritional properties of foods may be to modify the starch
      component, often included to stabilize the food product. In this study two
      chemically modified starches-a 1-2% acetylated potato starch and a starch
      enriched with 2% beta-cyclodextrin-and a native, unmodified potato starch
      (control) were investigated with regard to 6-h energy expenditure, substrate
      metabolism, hormone concentrations, and subjective appetite sensations. Subjects
      were 11 healthy, normal-weight, young men. The starch (50 g) was prepared as a
      pudding with fruit sauce and whipped cream (3180 kJ, 49% of energy from
      carbohydrate, and 40% of energy from fat). The meal was given in the morning
      after a 2-d carbohydrate-rich, weight-maintenance diet. After the modified-starch
      meals, response patterns for plasma glucose (P < 0.01), insulin (P < 0.05);
      gastric inhibitory polypeptide (P < 0.05), subjective satiety (P < 0.05), and
      fullness (P = 0.06) were significantly different from response patterns after the
      meal with the control starch. Thus, a flattening of the glucose curve, a lower
      insulin and gastric inhibitory polypeptide response, and higher fullness ratings
      were observed after the meal with the beta-cyclodextrin starch. Satiety ratings
      were higher after both meals with modified starch than after the meal with the
      control starch. In conclusion, a minor modification insulinemic (1-2%) of native
      potato starch improved the glycemia, insulinemic, and satiating properties of a
      meal. This was especially true for the beta-cyclodextrin-enriched starch. Slower
      gastric-emptying rate or delayed intestinal absorption of the modified starch may
      explain the observed differences.

PMID- 9250109
TI  - Effects of 4 y of oral supplementation with beta-carotene on serum concentrations
      of retinol, tocopherol, and five carotenoids.
AB  - beta-Carotene has been studied widely as a potential cancer-preventing agent.
      Recent studies found that subjects who took beta-carotene supplements orally had
      increases in their serum concentrations of alpha-carotene and lycopene that were
      large (> 150% increase) and significantly greater than such increases in subjects
      who received placebo and that similar supplementation was associated with a
      decrease of approximately 37% in plasma lutein concentrations. A biologic
      interaction between beta-carotene and other carotenoids was suggested. We
      measured concentrations of retinol, alpha-tocopherol, and five carotenoids in
      serum specimens from a random sample of subjects enrolled in a clinical trial of
      the use of antioxidant vitamins in preventing colonic adenomas. We used serum
      specimens obtained at enrollment and after the subjects took placebo (n = 54) or
      25 mg beta-carotene/d (n = 54) orally for 4 y. In a multivariate analysis,
      baseline serum concentrations of the analytes, sex, body mass index, diet,
      smoking status, and age were associated with variable changes in some analytes
      over the 4-y period but supplementation with beta-carotene was related only to a
      mean increase in serum beta-carotene itself of 151%. We excluded with 95%
      confidence an increase in lycopene > 4.9%, an increase in alpha-carotene > 17.6%,
      and a decrease in lutein > 14.7% in subjects given beta-carotene. These results
      confirm previous findings that supplementation with beta-carotene given orally
      does not alter serum concentrations of retinol or alpha-tocopherol. The findings
      also indicate that beta-carotene supplementation, which results in a moderate
      increase in serum beta-carotene concentration, does not significantly change
      serum concentrations of other carotenoids.

PMID- 9250110
TI  - Thiamine uptake in human intestinal biopsy specimens, including observations from
      a patient with acute thiamine deficiency.
AB  - Mucosal biopsy specimens obtained by routine endoscopy from 108 human subjects,
      including one patient with thiamine deficiency, were incubated at 37 degrees C in
      oxygenated calcium-free Krebs-Ringer solution (pH 7.5) containing tritiated
      thiamine and [14C]dextran as a marker of adherent mucosal water. The amount of
      labeled thiamine taken up was measured radiometrically. In subjects with no
      clinical evidence of thiamine deficiency, 1) thiamine uptake by duodenal mucosa
      had a hyperbolic time course, reaching equilibrium at 10 min; 2) thiamine
      concentrations < 2.5 mumol/L were taken up predominantly by a saturable mechanism
      displaying Michaelis-Menten kinetics (K(m) 4.4 mumol/L and Jmax 2.3 pmol.mg wet
      tissue-1.6 min-1), whereas higher concentrations were taken up by passive
      diffusion; 3) thiamine transport had different capacities along the
      gastrointestinal tract (duodenum >> colon > stomach); and 4) thiamine uptake was
      competitively inhibited in the duodenum by thiamine analogs, albeit with a
      different order of potency compared with rats, and was blocked by 2,4
      dinitrophenol. In the thiamine-deficient patient, the duodenal saturable uptake
      was increased, with higher K(m) and Jmax values. In conclusion, physiologic
      concentrations of thiamine were transported in human small intestine by a
      specific mechanism dependent on cellular metabolism, whose transporters appear to
      be down-regulated.

PMID- 9250111
TI  - Calcium retention in relation to calcium intake and postmenarcheal age in
      adolescent females.
AB  - Achievement of maximal calcium retention during adolescence may influence the
      magnitude of peak bone mass and subsequently lower the risk of osteoporosis.
      Calcium retention is generally considered to reach a plateau at a certain calcium
      intake. To test this hypothesis, calcium balance was measured in 35 females with
      a mean (+/-SD) age of 12.7 +/- 1.2 y (range: 12-15 y) who consumed from 841 +/-
      153 to 2173 +/- 149 mg Ca/d. Subjects ate a basal diet that included a fortified
      beverage containing different amounts of calcium citrate malate. Twenty-one
      subjects were studied at two dietary calcium intakes with use of a crossover
      design. Results from a previous study in 14 subjects who were studied at only one
      calcium intake were included in the data analysis. Calcium retention was modeled
      as a nonlinear function of calcium intake that included a parameter representing
      mean maximal retention. Mean maximal calcium retention was 473 mg/d (95% CI: 245,
      701 mg Ca/d). At higher postmenarcheal ages, maximal calcium retention was lower
      but the intake required to achieve this was not affected. Calcium intake
      explained 79% and 6%, respectively, of the variation in fecal and urinary calcium
      excretion. Intake of 1200 mg Ca/d, the recommended dietary allowance for calcium
      published in 1989, resulted in a mean calcium retention that was 57% of the
      maximal value (95% CI: 25%, 89%). Intake of 1300 mg Ca/d was the smallest intake
      that allowed some adolescent females to achieve 100% of maximal calcium retention
      (95% CI: 26%, 100%). These data support the idea that calcium retention plateaus
      at a certain calcium intake although it continues to increase at intakes > 2 g/d.

PMID- 9250112
TI  - Iron depletion without anemia and physical performance in young women.
AB  - Studies in laboratory animals found that iron deficiency without anemia decreased
      oxidative capacity and increased reliance on carbohydrate as the substrate for
      energy, thereby causing impaired endurance. The purpose of this cross-sectional
      study was to investigate the relation between iron deficiency without anemia and
      physical performance in healthy active women aged 19-36 y. Iron-status assessment
      included determination of hemoglobin, hematocrit, transferrin saturation, and
      serum ferritin values. Dietary iron intake was assessed by frequency
      questionnaires and physical activity level was estimated by frequency
      questionnaires and 2-wk records. Fifteen women with normal iron status and 15
      women with iron depletion (serum ferritin < 12 micrograms/L) were chosen randomly
      from a group of 69 nonanemic women and given physical-performance tests,
      including determinations of maximum oxygen consumption (VO2max), ventilatory
      threshold, and delta-efficiency. There were no significant differences between
      the two groups in body size, body composition, physical activity level, dietary
      iron intake, delta-efficiency, or ventilatory threshold. Compared with the iron
      depleted group, the iron-sufficient group had significantly higher hemoglobin,
      transferrin saturation, and serum ferritin values and a significantly greater
      tendency to use iron supplements. When physical activity level and fat-free mass
      were controlled for, the iron-depleted group had a significantly lower VO2max.
      The difference in VO2max was significantly associated with serum ferritin
      concentration; hemoglobin value was not a significant confounder. Therefore,
      reduction of VO2max in nonanemic women with iron depletion was likely caused by
      factors related to reduced body iron storage but was unrelated to decreased
      oxygen-transport capacity of the blood.

PMID- 9250113
TI  - Percentile estimates for transferrin receptor in normal infants 9-15 mo of age.
AB  - To establish percentile estimates of transferrin receptor (TfR) for healthy
      infants, plasma TfR was measured in 485 healthy infants 9-15 mo of age from
      Edmonton, Toronto, Montreal, and Halifax. Education and income of the sample
      families were reflective of the average family based on the 1991 census
      estimates. The mean (+/-SD) plasma TfR concentration was 4.4 +/- 1.1 mg/L. As
      expected in the infant population, there were no differences in TfR
      concentrations as a result of sex, and within this small age range there was no
      significant change across age. Furthermore, the TfR concentration in plasma was
      not associated with hemoglobin, serum ferritin, or free erythrocyte
      protoporphyrin. TfR has been shown to be a sensitive, quantitative measure of
      tissue iron deficiency not affected by inflammation and is potentially important
      in the diagnosis of iron deficiency, but there is a lack of normative data,
      particularly in infants, who are at highest risk of iron deficiency. If TfR
      proves useful in the diagnosis of iron deficiency, the current data will be
      useful as a reference standard for healthy infants.

PMID- 9250114
TI  - Iron absorption from the whole diet in men: how effective is the regulation of
      iron absorption?
AB  - Iron absorption from the whole diet, which contained a highly bioavailable form
      of iron, was measured for 5 d in 31 health men, including 12 blood donors.
      Nonheme iron in all meals was labeled with an extrinsic, inorganic radioiron
      tracer added in amounts to ensure uniform specific activity in all meals. Heme
      iron was labeled similarly by using hemoglobin biosynthetically labeled with
      another radioiron tracer. There was a good inverse relation between total
      absorption and concentration of serum ferritin up to approximately 60
      micrograms/L. In subjects with serum ferritin > 60 micrograms/L there was no
      relation to iron absorption. At this serum ferritin concentration, absorption
      decreased to a level just sufficient to cover basal iron losses, implying that at
      a serum ferritin concentration > or = 60 micrograms/L no further accumulation of
      iron stores will occur by dietary iron absorption. The findings thus suggest that
      in normal subjects there is no risk of developing iron overload by iron
      absorption from the diet even if the diet is fortified. Similar findings were
      made previously in two studies in women, both of which indicated an effective
      control of absorption. At the same serum ferritin concentration the absorption
      per kilogram body weight was the same in men and women served identical diets
      with a high iron bioavailability. These new observations strongly suggest that
      translation of serum ferritin concentration into amounts of stored iron should be
      made with caution and that in subjects with high serum ferritin concentrations,
      other causes than increased iron stores should be considered. There was effective
      control of both heme- and nonheme-iron absorption but their relations to iron
      status were different.

PMID- 9250115
TI  - Postprandial lipemia in relation to sterol and fat excretion in ileostomy
      subjects given oat-bran and wheat test meals.
AB  - To investigate the mechanisms behind the serum cholesterol-lowering effect of oat
      fiber, we simultaneously measured postprandial lipid responses, serum lathosterol
      concentrations, and small bowel excretion of fat and sterols in ileostomy
      subjects given test meals high or low in oat fiber. Six ileostomy subjects (three
      women and three men) were served an oat-bran test meal (OB; 16.3 g fiber) and a
      wheat test meal (6.3 g fiber) in random order. After the postprandial 7-h period,
      a controlled, low-fat, cholesterol-free diet was served and ileostomy effluent
      was sampled throughout the 24-h period. Bile acid and fat excretion (24 h)
      increased by 93% and 146%, respectively (P < 0.05), and total and endogenous
      cholesterol excretion decreased by 14% and 19%, respectively (P < 0.05), after
      the OB test meal. The change in hepatic cholesterol synthesis was strongly
      related to the change in bile acid excretion (Spearman r = 0.89, P < 0.02). The
      postprandial chylomicron lipid concentration tended to be lower after the OB test
      meal (-43% for cholesterol, P = 0.07) whereas there was no difference in
      cholesterol absorption measured by isotope in five subjects. The main effect of
      the viscous oat beta-glucan seems to be related to increased bile acid excretion
      and subsequent changes in synthesis and endogenous excretion of cholesterol. An
      additional effect may have been a delay in the micellar lipid solubilization
      process and a consequent reduction in the secretion of chylomicrons into the
      circulation.

PMID- 9250116
TI  - Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption
      on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention
      Study.
AB  - We determined whether serum carotenoid or retinol concentrations were altered by
      beta-carotene supplementation in the Alpha-Tocopherol, Beta-Carotene Cancer
      Prevention Study and whether such effects were modified by alcohol consumption or
      cigarette use. Participants in this substudy were 491 randomly selected men aged
      58-76 y from the metropolitan Helsinki study center [237 receiving supplemental
      beta-carotene (20 mg/d) and 254 not receiving such supplementation]. Dietary
      carotenoids, retinol, and alcohol, and serum beta-carotene, alpha-tocopherol,
      retinol, and cholesterol were assessed at baseline. After an average of 6.7 y of
      supplementation, serum was collected and carotenoid, retinol, and alpha
      tocopherol concentrations were determined by HPLC. Serum carotenoid fractions
      were highly correlated with each other (P < or = 0.0001). Compared with the
      unsupplemented group, the beta-carotene group had significantly higher serum
      concentrations of beta-carotene (1483%), alpha-carotene (145%), and beta
      cryptoxanthin (67%) (P < or = 0.0001). Retinol concentrations were 6% higher (P =
      0.03) and lutein was 11% lower (P = 0.02) in the supplemented group. Serum
      lycopene, zeaxanthin, and alpha-tocopherol did not differ according to beta
      carotene-supplementation status. Although these beta-carotene-group differences
      were not significantly altered by amount of alcohol consumption, higher
      consumption (> 12.9 g/d, median) was related to lower (10-38%) concentrations of
      carotenoids, particularly beta-carotene, alpha-carotene, and beta-cryptoxanthin,
      in both the supplemented and unsupplemented groups. Smoking status did not
      significantly influence the supplementation-related differences in serum
      carotenoid and retinol values but concentrations of carotenoids were generally
      highest in participants who quit smoking while in the study and lowest in current
      smokers of > or = 20 cigarettes/d. This study showed that serum concentrations of
      non-beta-carotene carotenoids are altered by long-term beta-carotene
      supplementation and confirms the adverse effects of alcohol and cigarette smoking
      on serum carotenoids.

PMID- 9250118
TI  - Is there an energy deficiency in homozygous sickle cell disease?
AB  - The low weight, low height-for-age, delayed skeletal maturation, and retarded
      puberty in children with homozygous sickle cell disease are consistent with
      chronic malnutrition. Voluntary energy intake in sickle cell patients (SS)
      appears to be similar to that of control subjects with a normal hemoglobin
      genotype (AA) despite a higher resting metabolic rate (RMR), which suggests a
      suboptimal nutritional state. Patients may therefore conserve energy by reducing
      physical activity; this hypothesis was tested by comparing RMR, total daily
      energy expenditure (TDEE), and physical activity level (TDEE:RMR) in 16
      postpubertal boys with sickle cell disease with those in 16 normal control
      subjects matched for age, sex, and pubertal stage. The RMR of sickle cell
      patients measured by indirect calorimetry (mean +/- SD: 7.0 +/- 0.9 MJ/d)
      significantly exceeded that of the normal control subjects (6.3 +/- 0.5 MJ/d; P =
      0.018) but TDEE measured by the heart rate method was greater in the control
      subjects (13.8 +/- 4.9 MJ/d) than in the sickle cell patients (10.5 +/- 2.2 MJ/d;
      P = 0.034). Physical activity level was 46% greater in control subjects (2.2 +/-
      0.8) than in sickle cell patients (1.5 +/- 0.3; P = 0.006). Adjustment for
      genotype differences in body weight reduced the genotype difference in physical
      activity level from 0.70 (95% CI: 0.3, 1.1) to 0.6 (95% CI: -0.06, 1.2). Reducing
      physical activity is a compensatory mechanism in children with an energy
      deficiency and a similar adaptive response may occur in sickle cell disease.

PMID- 9250117
TI  - Dietary compliance and cardiovascular risk reduction with a prepared meal plan
      compared with a self-selected diet.
AB  - Noncompliance with therapeutic diets remains a major obstacle to achieving
      improvements in cardiovascular disease (CVD) morbidity and mortality. This study
      compared dietary compliance and CVD risk factor response to two dietary
      interventions designed to treat hypertension, dyslipidemia, and diabetes
      mellitus. In a multicenter trial, 560 adults were randomly assigned to either a
      self-selected, mixed-food plan (n = 277), or a nutrient-fortified prepared meal
      plan (n = 283); each was designed to provide 15-20% of energy from fat, 55-60%
      from carbohydrate, and 15-20% from protein. Nutrient intake was estimated from 3
      d food records collected biweekly throughout the 10-wk intervention. Compliance
      was determined by evaluating the participants' ability to meet specific criteria
      for energy intake [+/-420 kJ (100 kcal) from the midpoint of the prescribed
      energy range], fat intake (< 20%, < 25%, or < 30% of energy from total fat), and
      the National Cholesterol Education Program/American Heart Association Step 1 and
      2 diet recommendations. Compliance with energy, fat, and Step 1 and 2 criteria
      was better in participants who followed the prepared meal plan than in those who
      followed the self-selected diet (P < 0.0001). Compliant participants in both
      groups achieved greater reductions in body weight, systolic and diastolic blood
      pressure, and total and low-density-lipoprotein cholesterol than noncompliant
      participants (P < 0.05). In general, better endpoint responses were observed with
      lower fat intakes regardless of group assignment. The prepared meal plan is a
      simple and effective strategy for meeting the many nutrient recommendations for
      CVD risk reduction and improving dietary compliance and CVD endpoints.

PMID- 9250119
TI  - Taste responses to naringin, a flavonoid, and the acceptance of grapefruit juice
      are related to genetic sensitivity to 6-n-propylthiouracil.
AB  - Increased consumption of vegetables and fruit has long been the focus of dietary
      strategies for disease prevention. Some vegetables and fruit have bitter tastes,
      which can be aversive to consumers, particularly children. The present study
      tested the hypothesis that acceptance of grapefruit juice is influenced, in part,
      by sensitivity to the bitter taste of 6-n-propylthiouracil (Prop), a heritable
      trait. A sample of 123 women, mean age 28 y, was divided into nontasters (n =
      39), tasters (n = 49), and supertasters (n = 35) of Prop by using procedures
      validated previously based on Prop detection thresholds and on intensity scaling
      of five suprathreshold solutions of Prop and sodium chloride. The subjects tasted
      and rated five solutions of the bioflavonoid naringin in 4% sucrose. Naringin,
      the principal bitter ingredient of grapefruit juice, has been implicated in the
      regulation of cytochrome P-450 enzymes. Increased taste acuity for both Prop and
      naringin was associated with greater dislike for each bitter compound. Prop
      supertasters disliked bitter naringin solutions significantly more than did
      either tasters or nontasters. Prop sensitivity was also associated with reduced
      acceptability of grapefruit juice. Acceptability of orange juice, which does not
      contain naringin, was unrelated to Prop taster status. Is the acceptability of
      other bitter vegetables and fruit also limited by inherited taste factors? If so,
      then genetic taste markers might limit dietary exposure to valuable dietary
      constituents and pose a barrier to current strategies for dietary change.

PMID- 9250121
TI  - Body composition, resting metabolic rate, and energy requirements of short- and
      normal-stature, low-income Guatemalan children.
AB  - We examined body composition using bioelectrical impedance analysis and isotope
      dilution (18O and 2H), resting metabolic rate (RMR) by indirect calorimetry, and
      total energy expenditure (TEE) by doubly labeled water in 15 short-stature
      (height-for-age < or = -1.5 SD) and 15 normal-stature (height-for-age > -1.5 SD)
      Guatemalan children aged 4-6 y. Although, in absolute terms significant group
      differences were found in fat-free mass (FFM), fat mass, and total body water
      (TBW), there were no significant differences in fat mass and TBW after adjustment
      for FFM. RMR of the short-stature children (3791 +/- 376 kJ/d) was not
      significantly different from that of normal-stature children (4038 +/- 531 kJ/d),
      and the regression between RMR and FFM was also not significantly different
      between groups. TEE was not significantly different in short-stature (4753 +/-
      761 kJ/d) compared with normal-stature children (5304 +/- 1020 kJ/d); the
      regression between TEE and FFM was not significantly different between the two
      groups. There were no significant group differences in RMR and TEE after
      adjustment for FFM. FFM was the strongest predictor of TEE, but could only
      explain 29% of the variance. We conclude that 1) the lower TBW and fat mass in
      the short-stature group is proportional to their lower FFM, 2) there is no
      significant difference in either RMR or TEE between short- and normal-stature
      children, and 3) TEE is highly variable among these children and cannot be
      explained by differences in body size alone.

PMID- 9250120
TI  - Effects of garlic thioallyl derivatives on growth, glutathione concentration, and
      polyamine formation of human prostate carcinoma cells in culture.
AB  - This study investigated whether naturally occurring garlic derivatives and
      synthetic S-cysteinyl compounds that resemble garlic constituents have
      antiproliferative effects on human prostate carcinoma (LNCaP) cells. Studies also
      examined whether S-allylmercaptocysteine and S-allylcysteine affect two important
      molecular targets, namely reduced glutathione and polyamines. Results showed that
      S-allylmercaptocysteine (50 mg/L) diminished LNCaP cell growth whereas the
      antiproliferative effect of S-allylcysteine was not as pronounced. Studies using
      synthetic S-cysteinyl analogues revealed that growth inhibition was most
      effective with compounds containing a disulfide or an active diallyl moiety.
      Marginal to no inhibitory effect was observed with monosulfinic analogues. Both S
      allylmercaptocysteine and S-allylcysteine caused an increase in LNCaP cell
      reduced glutathione concentrations. Putrescine and spermine concentrations
      decreased and spermidine increased 3 d after S-allylmercaptocysteine treatment.
      At 5 d after S-allylmercaptocysteine treatment, polyamine concentrations were
      similar to those of saline-treated controls. Diminished cell growth and altered
      polyamine concentrations suggest that S-allylmercaptocysteine may impede the
      polyamine synthesizing enzyme, ornithine decarboxylase, either by enhancing the
      formation of reduced glutathione, a known inhibitor of ornithine decarboxylase,
      or by reacting directly with ornithine decarboxylase at its nucleophilic thiol
      moiety. Because S-allylcysteine also increases reduced glutathione formation but
      does not significantly inhibit growth, the latter mechanism may be more likely
      for this compound. These data provide further evidence that nonessential
      nutrients derived from garlic may modulate tumor growth. Further research is
      required on effects of garlic derivatives in vivo before information from the
      present studies can be used to assist in the development of effective nutritional
      strategies for preventing progression of prostate cancer.

PMID- 9250122
TI  - Efficacy of zinc supplementation in reducing the incidence and prevalence of
      acute diarrhea--a community-based, double-blind, controlled trial.
AB  - A community-based, double-blind, randomized trial was conducted in a population
      of low socioeconomic status in urban India to determine whether daily zinc
      supplementation reduces the incidence and prevalence of acute diarrhea,
      especially in those with zinc deficiency. Children 6-35 mo of age were randomly
      assigned to zinc (n = 286) and control (n = 293) groups and received a supplement
      daily for 6 mo. Zinc gluconate (10 mg elemental Zn) was given, with both zinc and
      control groups also receiving multivitamins. The primary outcome measures
      determined by home visits every fifth day and physician examinations were the
      number of acute diarrheal episodes (incidence) and total diarrheal days
      (prevalence). Zinc supplementation had no effect in children 6-11 mo old. In
      children aged > 11 mo there was significantly less diarrhea in the zinc group. In
      boys > 11 mo old, supplementation resulted in a 26% (95% CI: 13%, 38%) lower
      diarrheal incidence and a 35% (95% CI: 20%, 50%) lower prevalence. In zinc
      supplemented girls > 11 mo of age, the incidence was 17% (95% CI: 2%, 30%) lower
      and the prevalence was 19% (95% CI: 4%, 47%) lower. Overall, zinc supplementation
      resulted in a 17% (95% CI: 1%, 30%) lower diarrheal incidence in children with
      plasma zinc concentrations < 9.18 mumol/L at enrollment and a 33% (95% CI: 6%,
      52%) lower incidence in children with concentrations < 50 mumol/L. In conclusion,
      zinc supplementation had a significant effect on acute diarrheal morbidity in
      children > 11 mo old and in children with low plasma zinc concentrations.

PMID- 9250123
TI  - How little we know about the absorption of iron.

PMID- 9250124
TI  - Food provision in dietary intervention studies.

PMID- 9250125
TI  - Malnutrition in sickle cell disease patients.

PMID- 9250126
TI  - The stinking rose: organosulfur compounds and cancer.

PMID- 9250127
TI  - Vitamins and minerals: efficacy and safety.
AB  - Safety and efficacy are crucial but separate issues for vitamin and mineral
      supplements. Misinterpretation of "safe and adequate" to mean "safety limit"
      would impose restrictions on vitamin and mineral intakes that are not needed to
      ensure safety. Substantial evidence indicates that intakes greater than the
      recommended dietary allowances (RDAs) of certain vitamins and minerals such as
      calcium, folic acid, vitamin E, selenium, and chromium reduce the risk of certain
      diseases for some people. Limitation of intakes to the RDAs would preclude
      reductions in disease risk from these nutrients. The margin of safety between the
      usual dietary intake and the intake that would produce adverse effects varies
      greatly among the different nutrients. Very high intakes of vitamins A and D,
      niacin, pyridoxine, and selenium have produced adverse effects. Many widely
      discussed putative adverse effects of vitamin C, vitamin E, and trivalent
      chromium have little factual basis. There is no evidence of adverse effects from
      beta-carotene supplements except in current heavy smokers.

PMID- 9250128
TI  - Regulation of cholesterol biosynthesis by diet in humans.
AB  - Biosynthesis of cholesterol represents a major input into whole-body pools;
      however, its regulation has been difficult to study in humans because of
      limitations in methodologies. The present objectives are to compare available
      techniques for measuring this process and examine how dietary factors alter human
      cholesterol biosynthesis. Review of existing techniques suggests that mass
      isotopomer distribution analysis and deuterium incorporation approaches offer
      advantages over other methods. Dietary factors influencing human cholesterol
      synthesis include energy restriction, meal frequency, dietary fat type, and
      cholesterol and phytosterol content. Food deprivation for as short as 24 h
      results in almost complete cessation of cholesterol biosynthesis. Similarly,
      increased meal frequency patterns are associated with a substantial depression in
      synthesis. In contrast, consumption of oils rich in polyunsaturated fatty acids,
      despite reducing circulating concentrations, increases the cholesterol synthesis
      rate compared with other fats. Stepwise addition of dietary cholesterol is
      associated with only a modest decline in cholesterogenesis while raising plasma
      concentrations slightly. It can be concluded that synthesis, as a contributor to
      circulating cholesterol concentrations, is sensitive to many dietary factors.
      Energy deprivation results in the greatest decline in synthesis, likely
      accounting for the beneficial decline in circulating cholesterol concentrations
      observed with weight loss.

PMID- 9250129
TI  - Red wine but not white: the importance of fully characterizing wines used in
      health studies.

PMID- 9250130
TI  - Dietary fat and health.

PMID- 9250131
TI  - Nutrition and cognitive function in the elderly.

PMID- 9250132
TI  - Vitamin B-12 fortification of folate-enriched grain products.

PMID- 9250133
TI  - Nutrition and the immune system: an introduction.
AB  - Nutrition is a critical determinant of immune responses and malnutrition the most
      common cause of immunodeficiency worldwide. Protein-energy malnutrition is
      associated with a significant impairment of cell-mediated immunity, phagocyte
      function, complement system, secretory immunoglobulin A antibody concentrations,
      and cytokine production. Deficiency of single nutrients also results in altered
      immune responses: this is observed even when the deficiency state is relatively
      mild. Of the micronutrients, zinc; selenium; iron; copper; vitamins A, C, E, and
      B-6; and folic acid have important influences on immune responses. Overnutrition
      and obesity also reduce immunity. Low-birth-weight infants have a prolonged
      impairment of cell-mediated immunity that can be partly restored by providing
      extra amounts of dietary zinc. In the elderly, impaired immunity can be enhanced
      by modest amounts of a combination of micronutrients. These findings have
      considerable practical and public health significance.

PMID- 9250134
TI  - Synergism of nutrition, infection, and immunity: an overview.
AB  - Infections, no matter how mild, have adverse effects on nutritional status. The
      significance of these effects depends on the previous nutritional status of the
      individual, the nature and duration of the infection, and the diet during the
      recovery period. Conversely, almost any nutrient deficiency, if sufficiently
      severe, will impair resistance to infection. Iron deficiency and protein-energy
      malnutrition, both highly prevalent, have the greatest public health importance
      in this regard. Remarkable advances in immunology of recent decades have
      increased insights into the mechanisms responsible for the effects of infection.
      These include impaired antibody formation; loss of delayed cutaneous
      hypersensitivity; reduced immunoglobulin concentrations; decreased thymic and
      splenic lymphocytes; reduced complement formation, secretory immunoglobulin A,
      and interferon; and lower T cells and T cells subsets (helper, suppressor
      cytotoxic, and natural killer cells) and interleukin 2 receptors. The effects
      observed with single or multiple nutrient deficiencies are due to some
      combination of these responses. In general, cell-mediated and nonspecific
      immunity are more sensitive than humoral immunity.

PMID- 9250135
TI  - Nutrition and immunity in the elderly: modification of immune responses with
      nutritional treatments.
AB  - Nutrition has a strong influence on the immune system of the elderly. Aging
      induces dysregulation of the immune system, mainly as a result of changes in cell
      mediated immunity. Aging is associated with changes to the equilibrium of
      peripheral T and B lymphocyte subsets, such as decreases in the ratios of mature
      to immature, naive to memory, T helper 1 subset (TH1) to TH2, and CD5- to CD5+
      cells. As a consequence, cell-mediated immune responses are weaker and neither
      cell-mediated nor humoral responses are as well adapted to the antigen stimulus.
      Undernutrition, common in aged populations, also induces lower immune responses,
      particularly in cell-mediated immunity. Protein-energy malnutrition is associated
      with decreased lymphocyte proliferation, reduced cytokine release, and lower
      antibody response to vaccines. Micronutrient deficits, namely of zinc, selenium,
      and vitamin B-6, all of which are prevalent in aged populations, have the same
      influence on immune responses. Because aging and malnutrition exert cumulative
      influences on immune responses, many elderly people have poor cell-mediated
      immune responses and are therefore at a high risk of infection. Nutritional
      therapy may improve immune responses of elderly patients with protein-energy
      malnutrition. Supplementation with high pharmacologic doses of a single nutrient
      (zinc or vitamin E) may be useful for improving immune responses of self
      sufficient elderly people living at home. Therefore, nutritional deficiency must
      be treated in the elderly to reduce infectious risk and possibly slow the aging
      process.

PMID- 9250136
TI  - Interactions between nutrition and immunity in anorexia nervosa: a 1-y follow-up
      study.
AB  - Nutritional status and immunocompetence were evaluated in 15 patients suffering
      from anorexia nervosa in comparison with a control group (n = 15). After 1 y,
      data from six phases of the study were evaluated: immediately after admittance to
      the hospital (AN1), after 1 mo (AN2), after 2 mo (AN3), after 3 mo (AN4), after 6
      mo (AN5), and after 1 y, (AN6). Patients recovered weight from AN4 until AN6
      although, according to body mass index values, all patients had low weights
      during the 1-y follow-up. Likewise, leukocyte and lymphocyte values were
      borderline and lower in patients in all phases tested than in control subjects.
      All lymphocyte subpopulations were lower in AN1 and AN2 patients (inpatients)
      than in control subjects, except for CD19 cells, which remained unmodified. There
      seemed to be a recovery of lymphocyte subsets after hospitalization in AN3 and
      AN4 patients (outpatients), except for CD57, which remained below control values.
      However, there was a global decrease of the lymphocyte subsets in AN5 and AN6.
      Ratios of CD4 to CD8 cells were not altered but the ratio of CD2 to CD19 cells
      was lower in all phases except AN6. Moreover, cell-mediated immune function was
      impaired and none of the patients showed normal responses. Thus, despite the
      slight weight increase found in AN4, AN5, and AN6 and the apparent cell subset
      recovery after hospitalization, these results suggest a greatly depleted
      nutritional status that remained during the whole year in all patients.

PMID- 9250137
TI  - Evaluation of nutritional status by immunologic assessment in bulimia nervosa:
      influence of body mass index and vomiting episodes.
AB  - The nutritional status of 21 patients suffering from bulimia nervosa was
      evaluated by anthropometric and immunologic indexes in comparison with a control
      group (n = 15). In addition, the influence of body mass index (BMI; in kg/m2)
      values and vomiting episodes on the nutritional status of bulimic patients was
      assessed. Anthropometry showed no signs of malnutrition in either group, except
      for those patients with low weights (BMI < 19). Bulimic patients had lower
      lymphocyte counts than did control subjects, except for those without vomiting
      (NVBN). All T lymphocyte subsets tested as well as CD57 cells were lower (22% and
      55%, respectively) in bulimic patients than in control subjects, but the CD19
      cell subset remained unmodified. The low-weight bulimic group (LWBN) had lower
      CD4 cell counts than did the normal-weight (BMI > 19) bulimic group. The NVBN
      group had lymphocyte subpopulations similar to those in the control group, except
      for CD57, which was lower. The bulimic patients with vomiting had the lowest cell
      subset values. These results suggest a depleted nutritional status in all bulimic
      patients studied, even those with normal weights. The LWBN group had the most
      depleted nutritional status and the NVBN group was least affected at a
      subclinical level. CD57 can be considered a good marker of nutritional status in
      this syndrome because it was the only subpopulation altered in all groups.

PMID- 9250138
TI  - Cross-sectional assessment of nutritional and immune status in renal patients
      undergoing continuous ambulatory peritoneal dialysis.
AB  - Malnutrition prevalence and immunocompetence were assessed in uremic patients
      undergoing continuous ambulatory peritoneal dialysis (CAPD). Forty-two males and
      twenty-four females with kidney disease treated with CAPD were distributed into
      three groups according to the length of time they had been undergoing dialysis.
      Group 0 included patients beginning dialysis; group 1, patients undergoing CAPD
      for < 30 mo; and group 2, patients undergoing CAPD for > 30 mo. Body weight and
      body mass index were greater in patients who had been undergoing CAPD for longer
      periods of time (approximately 11% in males and 14% in females), which was
      accompanied by higher fat stores and muscle mass when assessed through triceps
      skinfold thickness and arm muscle measurements. These differences were more
      apparent in females than in males. Immunoglobulin M values were lower in patients
      in groups 1 and 2 than in group 0, whereas retinol binding protein, fibronectin,
      and C4 were higher. Estimated protein intake was higher in predialysis patients
      (1.31 g.d-1.kg-1) than in the other groups (approximately 0.95 g.d-1.kg-1). The
      percentage of B cells decreased with time on dialysis. Although no changes in
      total or helper T cells were found, a significant rise was noted for the T cell
      subpopulation with assumed suppressor and cytotoxic activities and for natural
      killer cells in those patients undergoing longer periods of CAPD treatment.
      Alterations in immune cell numbers in immunoglobulins and complement proteins
      might be responsible for immunologic disturbances and infectious processes
      occurring in patients with chronic renal failure and undergoing CAPD.

PMID- 9250139
TI  - Human immunodeficiency virus infection and nutritional status in female drug
      addicts undergoing detoxification: anthropometric and immunologic assessments.
AB  - To clarify the interrelations among drug abuse, malnutrition, and
      immunosuppression, the effects of human immunodeficiency virus (HIV) infection on
      the nutritional status of 17 noninfected and 19 HIV-infected asymptomatic female
      drug addicts undergoing detoxification were evaluated by measuring anthropometric
      and immunologic indexes. Anthropometric measurements were normal in both groups
      as a result of weight gain (approximately 10 kg) in every patient after the
      detoxification period. Leukocyte and lymphocyte values and CD2 lymphocyte subset
      counts were also similar in both groups. CD4 counts (P = 0.04) and the ratio of
      CD4 to CD8 cells (P = 0.6 x 10(-4)) were lower whereas CD8 counts (P = 0.003)
      were higher in the HIV-infected than in the noninfected group. Responses to a
      delayed-hypersensitivity skin test were below normal in both groups but
      significantly more so in the HIV-positive group (P = 0.05). CD19 counts were
      lower (P = 0.02) and values for serum immunoglobulins G and M were higher (51%
      and 37%, respectively) in the HIV-infected females than in the noninfected women.
      These results may suggest that despite anthropometric recovery, the HIV-infected
      women had depleted immune function, resulting not only from HIV infection but
      also from the subclinical malnutrition triggered by previous drug addiction.

PMID- 9250140
TI  - Effects of human immunodeficiency virus infection and detoxification time on
      anthropometric measurements and dietary intake of male drug addicts.
AB  - Anthropometric measurements and dietary intakes of male drug addicts (n = 62),
      infected (n = 23) or not infected (n = 39) with human immunodeficiency virus
      (HIV), who underwent two phases of detoxification (P1:15 d to 1 mo and P2: 5-6
      mo) were assessed. Body weight, weight gain during detoxification, height, body
      mass index, and ideal body weight were measured. A prospective food-record
      questionnaire was compiled and energy and nutrient contents of ingested food were
      determined. Food intakes were compared with dietary recommendations for the
      Spanish population. At the time of the study, all patients had substantial weight
      gains, mostly in P1. Nutrient consumption was lower in P2 (energy, protein, and
      lipids) and in groups not infected with HIV. In P2, lipid intake was higher in
      the HIV-positive than in the HIV-negative group (P < 0.05, Student's t test).
      Moreover, an interactive effect of HIV by phase was shown for lipid intake (P =
      0.04, two-way analysis of variance). Magnesium, folate, and vitamin E intakes
      were lower than recommended in nearly all patients. Energy, zinc, riboflavin, and
      vitamin B-6 intakes were lower than recommended or were borderline. HIV infection
      did not have a negative effect on anthropometric measurements or on nutrient
      intakes. The anthropometric assessment may suggest an adequate recovery of the
      indexes measured in all patients, which principally took place during P1.
      Measurement of nutrient intakes showed certain imbalances and deficits that
      should be corrected.

PMID- 9250141
TI  - Immune modulation of blood leukocytes in humans by lactic acid bacteria: criteria
      for strain selection.
AB  - Lactic acid bacteria in food can transiently colonize the intestine and exert
      beneficial effects (probiotic). Survival during intestinal transit or adhesion to
      epithelium or both seem to be important for modifying the host's immune
      reactivity. Because Lactobacillus acidophilus strain La1 is adherent to
      enterocytes in vitro, we hypothesize that contact with immune cells may occur in
      vivo. However, Bifidobacterium bifidum strain Bb12, which shows high fecal
      colonization, is another potential immunomodulator. Twenty-eight volunteers were
      divided into two groups and given a fermented product containing one of the two
      strains. Lymphocyte subsets and leukocyte phagocytic activity were studied in
      blood. No modifications were detected in lymphocyte subsets. In contrast,
      phagocytosis of Escherichia coli ssp. was enhanced in both groups (P < 0.001 for
      both). Bacterial adhesion to enterocytes, fecal colonization, or both seem to be
      valuable selection criteria for immunomodulation. Antiinfective mechanisms of
      defense can be enhanced after ingestion of specific lactic acid bacteria strains.

PMID- 9250142
TI  - Role of food in the stimulation of cytokine production.
AB  - To study the role of food in the stimulation of cytokine production, the effects
      of lactic bacteria on production of interferon alpha, beta, and gamma;
      interleukin 1 beta; and tumor necrosis factor alpha were evaluated in mice and
      humans. Yogurt bacteria induced plasma interferon alpha and beta production in
      mice. Yogurt intake containing 10(11) bacteria led to increased 2'-5' A
      synthetase activity in human blood mononuclear cells. This result may suggest an
      interferon action in a peripheral way. This effect was also found when subjects
      consumed 10(8) yogurt bacteria/d for 15 d. In an in vitro model, blood
      mononuclear cells cultured in the presence of yogurt bacteria produced
      interleukin 1 beta, tumor necrosis factor, and interferon alpha and gamma. These
      results suggest the involvement of a certain type of food in cytokine production
      under healthy conditions.

PMID- 9250143
TI  - Food hypersensitivity and allergic disease: a selective review.
AB  - Food intolerance can be caused by immunologic, pharmacologic, toxic, infectious,
      idiosyncratic, metabolic, and neuropsychologic processes. Food allergy denotes an
      adverse reaction to food or food additives in which an underlying immunologic
      mechanism can be shown. Its incidence in young children is approximately 1.3% and
      among adults is 0.3%. Parental history of atopy is a significant causal factor.
      In addition, exposure to common allergenic foods in infancy increases risk. For
      these reasons, exclusive breast-feeding and maternal avoidance of peanut, egg,
      fish, and dairy products during lactation has been recommended and shown to
      reduce the occurrence of food allergy. Wheat, egg, and fish should not be
      introduced until the infant is aged > 12 mo and peanut until the age of 36 mo.
      These measures and other environmental precautions can be expected to reduce the
      cumulative prevalence of allergy.

PMID- 9250144
TI  - Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of
      inflammation.
AB  - In this commentary, we have suggested that the fibroblast should be considered a
      sentinel cell. This concept is based on the fibroblast's ability to function both
      as a structural element and as a vital immunoregulatory cell. In some tissues,
      these capabilities may be ascribable to subsets of fibroblasts, rather than to
      some of the general fibroblast populations. The pioneering research of Xia et al,
      as well as that of others, highlights the need to explore the importance of
      fibroblasts as playing critical roles in disease. Emerging concepts regarding
      tissue-specific fibroblasts and fibroblast heterogeneity need to be considered in
      studies of their biosynthetic capabilities. Of special importance is the recent
      insight that the NF kappa B/RelB family of transcription proteins have apparently
      different regulatory roles in fibroblasts and hematopoietic cells. Therefore,
      with regard to therapeutic strategies targeting molecules such as RelB, caution
      should be exercised as their interruption may have very different consequences in
      macrophages compared with fibroblasts. For example, inhibition of RelB in
      macrophages may well prevent enhanced chemokine expression, whereas in
      fibroblasts, a critical governor for preventing chemokine expression would be
      lost. Overall, this could lead to exacerbation of inflammation rather than to an
      attenuation of the process.

PMID- 9250145
TI  - Molecular analysis of oral lichen planus. A premalignant lesion?
AB  - Oral lichen planus (OLP) is a common mucosal condition that is considered
      premalignant by some, although others argue that only lichenoid lesions with
      dysplasia are precancerous. To address the question of whether OLP without
      dysplasia is premalignant, we used microsatellite analysis to examine 33 cases of
      OLP for allelic loss at nine loci located on chromosomes 3p, 9p, and 17p. Loss of
      heterozygosity (LOH) on these three arms occurs frequently in oral tumors, and
      the presence of these alterations in premalignant lesions suggests that they may
      play an important role in tumor progression. Results were compared with those
      observed in oral dysplasias (10 mild, 11 moderate, 16 severe/carcinoma in situ),
      22 oral squamous cell carcinomas, and 29 reactive lesions. LOH was present in 6%
      of OLP, 14% of reactive lesions, 40% of mild dysplasia, 46% of moderate
      dysplasia, 81% of severe dysplasia/carcinoma in situ, and 91% of squamous cell
      carcinomas. LOH was detected on only a single arm in OLP and reactive lesions but
      occurred on more than one chromosome in dysplasia and cancer, and the frequency
      of this multiple loss correlated significantly with increasing degrees of
      dysplasia and progression into squamous cell carcinoma (P = 0.0028). Although
      these findings do not support OLP as a lesion at risk for malignant
      transformation, such results need to be confirmed by use of other genetic markers
      as OLP may undergo malignant transformation through genetic pathways different
      from those of oral dysplasia.

PMID- 9250146
TI  - Increased beta-catenin protein and somatic APC mutations in sporadic aggressive
      fibromatoses (desmoid tumors).
AB  - Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal
      proliferation of spindle (fibrocyte-like) cells that is locally invasive but does
      not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial
      adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a
      subset of aggressive fibromatoses suggests that the adenomatous polyposis coli
      (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular
      level of beta-catenin, which is a downstream mediator in Wnt (Wingless)
      signaling. beta-Catenin has a nuclear function (binds transcription factors) and
      a cell membrane function (is a component of epithelial cell adherens junctions).
      Six cases of aggressive fibromatosis of the extremities from patients without
      familial adenomatous polyposis, or a family history of colon cancer, were
      studied. Immunohistochemistry, using carboxy and amino terminus antibodies to
      APC, and DNA sequencing showed that three of the six contained an APC-truncating
      mutation, whereas normal tissues did not contain a mutation. Western blot and
      Northern dot blot showed that all six tumors had a higher level of beta-catenin
      protein than surrounding normal tissues, despite containing similar levels of
      beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the
      cell in tumor tissues, although it localized more to the periphery in cells from
      normal tissues. Reverse transcription polymerase chain reaction showed that the
      tumors expressed N-cadherin but not E-cadherin (a pattern of expression of
      proteins making up adherens junctions similar to fibrocytes), suggesting that the
      specific adherens junctions present in epithelial cells are not necessary for
      beta-catenin function. Increased beta-catenin may cause the growth advantage of
      cells in this tumor through a nuclear mechanism. The increased protein level,
      relative to the RNA level, suggests that beta-catenin is degraded at a lower rate
      compared with normal tissues. In some cases, this is caused by a somatic mutation
      resulting in a truncated APC protein.

PMID- 9250147
TI  - High-level DNA amplifications are common genetic aberrations in B-cell neoplasms.
AB  - Gene amplification is one of the molecular mechanisms resulting in the up
      regulation of gene expression. In non-Hodgkin's lymphomas, such gene
      amplifications have been identified rarely. Using comparative genomic
      hybridization, a technique that has proven to be very sensitive for the detection
      of high-level DNA amplifications, we analyzed 108 cases of B-cell neoplasms (42
      chronic B-cell leukemias, 5 mantle cell lymphomas, and 61 aggressive B-cell
      lymphomas). Twenty-four high-level amplifications were identified in 13% of the
      patients and mapped to 15 different genomic regions. Regions most frequently
      amplified were bands Xq26-28, 2p23-24, and 2p14-16 as well as 18q21 (three times
      each). Amplification of several proto-oncogenes and a cell cycle control gene (N
      MYC (two cases), BCL2, CCND2, and GLI) located within the amplified regions was
      demonstrated by Southern blot analysis or fluorescence in situ hybridization to
      interphase nuclei of tumor cells. These data demonstrate that gene amplifications
      in B-cell neoplasms are much more frequent than previously assumed. The
      identification of highly amplified DNA regions and genes included in the
      amplicons provides important information for further analyses of genetic events
      involved in lymphomagenesis.

PMID- 9250148
TI  - The monoclonal antibody ALK1 identifies a distinct morphological subtype of
      anaplastic large cell lymphoma associated with 2p23/ALK rearrangements.
AB  - Anaplastic large cell lymphoma (ALCL) is a heterogeneous group of diseases by
      morphology, phenotype, genotype, and clinical presentation. Using a new
      monoclonal antibody (ALK1) that recognizes the native anaplastic lymphoma kinase
      (ALK) protein as well as the fusion product of the t(2;5)(p23;q35), nucleophosmin
      (NPM)/ALK, we investigated for ALK expression cases diagnosed as ALCL as well as
      lympho-proliferative disorders possessing overlapping features with ALCL.
      Thirteen cases showed cytoplasmic staining of the neoplastic cells. These cases
      were characterized by a fairly uniform morphology and occurred in children and
      young adults as a systemic disease. All other cases comprising T or null ALCL (17
      cases), B ALCL (8 cases), Hodgkin's disease (HD) (15 cases), HD-like ALCL (23
      cases), and lymphomatoid papulosis (9 cases), were negative for ALK expression.
      Translocation t(2;5)(p23;q35) was found by classical cytogenetics or interphase
      fluorescence in situ hybridization in 8 of the ALK1-positive cases and by reverse
      transcription-polymerase chain reaction in 1 other case. Two additional ALK1
      positive cases with an abnormal karyotype, but without t(2;5)(p23;q35), showed by
      fluorescence in situ hybridization analysis a cryptic NPM/ALK gene fusion caused
      by an insertion of ALK near NPM in one case and a translocation of ALK to 2q35 as
      a result of an indiscernible inv(2)(p23q35) in the other. The latter variant
      translocation points to a localization of an unknown gene at 2q35 that, like NPM,
      might deregulate ALK and be involved in the pathogenesis of ALCL. In summary,
      immunohistochemistry with ALK1 antibody allows the identification of a distinct
      subgroup within the ALCL of T or null phenotype that is associated with 2p23
      abnormalities and lacks the marked histological pleomorphism described in ALCL in
      general. Whereas immunostaining is the most sensitive method to identify this
      group, it does not help to additionally clarify the relationship among ALCL, HD,
      and HD-like ALCL.

PMID- 9250149
TI  - Evaluation of the differentiation potential of WB-F344 rat liver epithelial stem
      like cells in vivo. Differentiation to hepatocytes after transplantation into
      dipeptidylpeptidase-IV-deficient rat liver.
AB  - After intrahepatic transplantation into livers of adult syngeneic German-strain
      Fischer 344 rats that are deficient for the bile canalicular enzyme dipeptidyl
      peptidase IV (DPP-IV), cultured WB-F344 rat liver epithelial cells (without
      exogenous marker genes) integrate into hepatic plates and differentiate into
      hepatocyte-like cells that are morphologically and functionally indistinguishable
      from mature hepatocytes. In this model system, the differentiated progeny of
      transplanted WB-F344 cells are identified among the DPP-IV-negative host
      hepatocytes by their expression of bile canalicular DPP-IV enzyme activity. DPP
      IV-positive hepatocyte-like cells also expressed other markers of hepatocytic
      differentiation, including albumin, transferrin, and alpha-1-antitrypsin,
      suggesting that the progeny of transplanted WB-F344 cells express a complete
      hepatocyte differentiation program. These results complement our previous studies
      indicating WB-F344 cells can serve as stem-like precursor cells for
      differentiated hepatocytes and strengthen the suggestion that WB-F344 rat liver
      epithelial cells represent the cultured counterpart of liver stem-like hepatocyte
      progenitor cells present in the normal adult rat liver.

PMID- 9250151
TI  - RelB regulation of chemokine expression modulates local inflammation.
AB  - The resolution of acute inflammation is incompletely understood but presumably
      requires the elimination of both inflammatory cells and production of
      inflammatory cytokines. In the case of recruited bone-marrow-derived inflammatory
      cells such as granulocytes and macrophages, their short life span helps eliminate
      these cells and the cytokines they produce. By contrast, resident permanent cells
      such as fibroblasts require other mechanisms to stop the production of chemokines
      generated in response to inflammatory triggers such as lipopolysaccharide. Here
      we demonstrate that RelB is an important regulator of chemokine expression in
      fibroblasts, thereby playing a key role in the resolution of acute inflammation.
      Activation of normal fibroblasts by lipopolysaccharide induced a transient
      production of chemokines, closely followed by induction of RelB expression.
      However, stimulated RelB-/- fibroblasts exhibited dramatic persistent induction
      of seven chemokines (RANTES, MIP-1 alpha, MIP-1 beta, MIP-2, IP-10, JE/MCP-1, and
      KC/CINC). The persistent overexpression of chemokines correlated with increased
      NF- kappa B binding as well as with increased p50, p65/RelA, and I kappa B alpha
      expression. Transfection of RelB cDNA into RelB-deficient fibroblasts reversed
      the lipopolysaccharide-induced chemokine overexpression. In vivo, activated RelB
      /- fibroblasts dramatically increased recruitment of granulocytes into tissues.
      In view of the apparent role of RelB in the resolution of acute inflammation in
      tissues and previous work showing a requirement for RelB in the initiation of
      immune responses through the differentiation of antigen-presenting cells, RelB
      may be an important factor regulating the transition from innate to adaptive
      immunity.

PMID- 9250150
TI  - Transfection of HepG2 cells with infectious hepatitis C virus genome.
AB  - Hepatitis C virus (HCV) represents one of the major causes of acute and chronic
      hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) around the world. Our
      knowledge of the life cycle of HCV, however, is limited. Current studies are
      hampered by the lack of a reproducible, high-level in vitro replication system of
      HCV. We sought to establish HCV replication in HepG2 cells by gene transfer of in
      vitro transcribed HCV RNA. In preliminary experiments, diethylaminoethyl-dextran
      led to more efficient gene transfer than cationic liposomes (lipofectin,
      lipofectamine, and DOTAP). Therefore, in subsequent experiments, HepG2 cells were
      transfected with full-length (9.6-kb) and near-full-length (9.4-kb) HCV RNA using
      diethylaminoethyl-dextran. Transfection with subgenomic HCV RNA and mock
      transfection were used as controls. Positive- and negative-strand HCV RNA
      sequences were detected by reverse transcription polymerase chain reaction (KT
      PCR) for 60 days in the infectious HCV RNA transfected HepG2 cells. The presence
      of negative-strand HCV RNA, presumably representing replicative intermediates,
      was confirmed by ribonuclease protection assay. The intracellular levels of HCV
      RNA were measured by quantitative competitive RT-PCR from 10 to 50 days after
      transfection and were stable over this time period at moderately high levels
      (10(8) to 10(10) genomes per mg of total RNA). Expression of viral core and
      nonstructural proteins was detected in the cytoplasm of transfected cells by
      immunostaining. Virus-like particles measuring 50 to 60 nm in diameter were found
      by electron microscopy in cytoplasmic vesicles and conditioned media of the cells
      transfected with infectious HCV RNA but not in cells transfected with truncated
      HCV RNA. Culture supernatants of infectious HCV RNA transfected HepG2 cells were
      infectious for Daudi cells for three passages tested. The truncated HCV RNA
      lacking NS5 and 3' untranslated region (3' UTR) of HCV was replication
      incompetent. This is the first demonstration of HCV particles in HepG2 cells
      after transfection with infectious HCV RNA. We conclude that we have established
      a reproducible HCV replication system in HepG2 cells that can be used to study
      the life cycle of HCV and to test anti-HCV agents.

PMID- 9250152
TI  - Asbestos causes translocation of p65 protein and increases NF-kappa B DNA binding
      activity in rat lung epithelial and pleural mesothelial cells.
AB  - The mechanisms of cell signaling and altered gene expression by asbestos, a
      potent inflammatory, fibrogenic, and carcinogenic agent, are unclear. Activation
      of the transcription factor, nuclear factor (NF)-kappa B, is critical in up
      regulating the expression of many genes linked to inflammation and proliferation.
      Inhalation models of crocidolite- and chrysotile-induced inflammation and
      asbestosis were used to study the localization of p65, a protein subunit of the
      NF-kappa B transcription factor, in sham control rats and those exposed to
      asbestos. In addition, we investigated, using electrophoretic mobility shift
      analysis, whether in vitro exposure of rat lung epithelial cells and rat pleural
      mesothelial cells to asbestos increased binding of nuclear proteins, including
      p65, to the NF-kappa B DNA response element. Furthermore, translocation of p65
      into the nucleus was determined by confocal microscopy. In comparison with sham
      animals, striking increases in p65 immunofluorescence were observed in airway
      epithelial cells of rats at 5 days after inhalation of asbestos. These increases
      were diminished by 20 days, the time period necessary for development of fibrotic
      lesions. In contrast, although inter-animal variability was observed,
      immunoreactivity for p65 was more dramatic in the interstitial compartment of
      asbestos-exposed rat lungs at both 5 and 20 days. Changes in p65 expression in
      pleural mesothelial cells exposed to asbestos in inhalation experiments were
      unremarkable. Exposure to asbestos also caused significant increases in nuclear
      protein complexes that bind the NF-kappa B consensus DNA sequence in both rat
      lung epithelial and rat pleural mesothelial cells. Using confocal microscopy, we
      observed partial nuclear translocation of p65 in rat pleural mesothelial cells
      exposed to asbestos. This partial response contrasted with the effects of
      lipopolysaccharide, which caused rapid and complete translocation of p65 from
      cytoplasm to nucleus. Our studies are the first to show the presence of the NF
      kappa B system in lung tissue and evidence of activation in vitro and in vivo
      after exposure to a potent inflammatory, fibrinogenic, and carcinogenic
      environmental agent.

PMID- 9250153
TI  - Loss of EDB+ fibronectin isoform is associated with differentiation of alveolar
      epithelial cells in human fetal lung.
AB  - Cell-matrix interactions have been shown to regulate the development of the lung,
      particularly airway branching and alveolarization. Fibronectin is the major
      constituent of pulmonary extracellular matrix and exists in multiple isoforms
      arising from alternative RNA splicing. EDA and EDB are the two major
      alternatively spliced segments, the expression of which is regulated in a
      spatiotemporal and oncodevelopmental manner. In this study, we investigated
      immunohistochemically the distribution of the EDA- and EDB-containing fibronectin
      isoforms (referred to as EDA+ fibronectin and EDB+ fibronectin, respectively) in
      normal and hypoplastic human lungs at different gestational ages to explore the
      role of these fibronectin isoforms in alveolarization. EDA+ fibronectin was
      expressed around the distal airspaces throughout the development of both normal
      and hypoplastic lungs. In contrast, the expression of EDB+ fibronectin was
      restricted to the lung with morphologically immature acinar complex, typically
      observed in normally developing lungs of < 30 gestational weeks or in hypoplastic
      lungs. To further confirm the restricted expression of EDB+ fibronectin in
      immature acinar complex, we examined the correlation of EDB+ fibronectin
      expression with that of the surfactant protein SP-A, a biochemical marker for the
      differentiated type II pneumocytes. A clear inverse relationship between the
      immunoreactivities for EDB+ fibronectin and SP-A was observed in both control and
      hypoplastic lungs. Given the proposed importance of fibronectins in the
      differentiation of alveolar epithelial cells, our results suggest that the EDB
      segment plays a regulatory role in the differentiation of immature acinar
      epithelial cells into type II pneumocytes. The EDB segment may also serve as a
      new histochemical marker for the functional maturity of fetal lung tissues.

PMID- 9250154
TI  - Mosaic pattern of ornithine transcarbamylase expression in spfash mouse liver.
AB  - Mosaicism of ornithine transcarbamylase expression was immunohistochemically
      examined in hepatocytes of spfash heterozygous female mouse livers. An
      immunohistochemical method using polyclonal antibodies against ornithine
      transcarbamylase visualized the mosaicism in serial paraffin sections. Very
      complicated mosaic patterns consisting of positive and negative hepatocytes were
      obtained in a section of adult liver, but a computer-aided three-dimensional
      analysis of serial sections demonstrated that patches with complicated shapes and
      various sizes, which are contiguous groups of positive or negative hepatocytes
      and are isolated in sections, connected very well with one another. No definite
      orientation such as portal-central was observed in the three-dimensional images
      of each patch. In balanced regions of the mosaicism, most individual plates along
      their straight portal-central lengths did not appear to be composed of only
      marker-positive or marker-negative hepatocytes. By contrast, in unbalanced
      regions of the mosaicism, individual plates along their total portal-central
      lengths often consisted entirely of a major type of hepatocytes. A patch appeared
      to be present in more than two lobules, but each patch did not constitute a
      complete lobule. Complicated mosaic patterns of patches were also seen in
      neonatal and postnatal livers. These results suggest that, although hepatocytes
      proliferate and migrate extensively during development, they might allocate their
      daughter cells contiguously and the orientation of their allocation might be
      random, leading to the formation of three-dimensionally large contiguous
      quasiclones of hepatocytes, the shapes of which are very complicated.

PMID- 9250155
TI  - Sinus-lining cells of the lymph nodes recognized as a dendritic cell type by the
      new monoclonal antibody Ki-M9.
AB  - In the immunobiological characterization of lymph node cells, sinus-lining cells
      (SLCs) have been given little attention mainly due to the difficulties in their
      recognition. Ki-M9 is a new monoclonal antibody (MAb) selected for its unique
      capability to visualize SLCs in human lymph nodes. The details were established
      by light and electron microscopy and immunoprecipitation of the corresponding
      biosynthetically labeled antigen. Ki-M9 recognizes a 70-kd protein localized on
      the surface membrane of SLCs. In the lymphoid tissue, a mild reactivity was
      exclusively encountered on follicular dendritic reticulum cells in the germinal
      centers of secondary lymphoid follicles. In other organs, some squamous
      epithelial and myoepithelial cells were recognized by this antibody.
      Immunomonitoring of SLCs on light and electron microscopic levels revealed their
      dendritic morphology, lack of phagosomes, and their close association with type
      IV collagen fibers. Considering the occurrence of typical dendritic SLCs on the
      front line of antigen flood, we propose that SLCs be investigated for a possible
      antigen-binding property.

PMID- 9250156
TI  - Intraepithelial lymphocytes in normal human intestine do not express proteins
      associated with cytolytic function.
AB  - Human small intestine contains a very large population of intraepithelial T
      lymphocytes (IELs) that are oligoclonal, appear functionally to be cytolytic T
      cells, and may contribute to the normal and pathological turnover of intestinal
      epithelial cells. This report addresses the cytolytic function of IELs in normal
      small intestine by examining their expression of molecules that carry out cell
      mediated cytolysis. Immunohistochemical analyses of granzyme B, perforin, Fas
      ligand, and tumor necrosis factor-alpha demonstrated these proteins were not
      expressed by small intestinal IELs in situ. These proteins also were not
      expressed by colonic IELs or by lamina propria lymphocytes in the small or large
      intestine. Granzyme A, however, was expressed by a large fraction of IELs. In
      contrast to these in situ results, isolated and in vitro activated IELs were
      shown to express effector proteins consistent with cytolytic T cells, including
      granzyme B, Fas ligand, tumor necrosis factor-alpha, and interferon-gamma. These
      results are most consistent with the vast majority of IELs in normal human small
      intestine being resting cytolytic T cells and suggest that these cells do not
      contribute to the apoptotic cell death of epithelial cells in normal intestine.

PMID- 9250157
TI  - Distribution of epidermal growth factor receptor and ligands during bronchiolar
      epithelial repair from naphthalene-induced Clara cell injury in the mouse.
AB  - Clara cells are primary targets for metabolically activated pulmonary toxicants
      because they contain an abundance of the cytochrome P450 monooxygenases required
      for generation of toxic metabolites. The factors that regulate bronchiolar
      regeneration after Clara cell injury are not known. Previous studies of
      naphthalene-induced bronchiolar injury and repair in the mouse have shown that
      epithelial cell proliferation is maximal 1 to 2 days after injury and complete 4
      days after injury. Proliferation is followed by epithelial re-differentiation (4
      to 14 days). In this study, mice were treated with the environmental pollutant
      naphthalene to induce massive Clara cell injury. The distribution and abundance
      of three growth-regulatory peptides (epidermal growth factor receptor (EGFR),
      epidermal growth factor (EGF), and transforming growth factor (TGF)-alpha) was
      determined immunochemically during repair of this acute bronchiolar injury. EGFR
      and its ligands were detected at low levels in cells throughout the lung
      including peribronchiolar interstitial cells, blood vessels, and conducting
      airway epithelium. Immediately after naphthalene injury (1 to 2 days), EGFR, EGF,
      and TGF-alpha are expressed in increased abundance in squamous epithelial cells
      of the injury target zone, distal bronchioles. These immunopositive squamous
      cells are detected in clumps in the distal bronchioles at the time when cell
      proliferation is maximal. EGFR protein expression is decreased slightly 4 to 7
      days after injury and continues to decrease below control levels of abundance 14
      to 21 days after injury. This down-regulation of EGFR is not reflected in a
      corresponding decrease in EGF and TGF-alpha protein expression, indicating that
      control of cell proliferation is regulated at the receptor level. Co-localization
      of EGFR and bromodeoxyuridine-positive proliferating cells in the same bronchiole
      indicates that EGFR is up-regulated within the proliferative microenvironment as
      well as in specific proliferating cells within the injury target zone. The
      coincident localization within terminal bronchioles of EGFR, EGF, and TGF-alpha
      to groups of squamous epithelial cells 2 days after naphthalene injury suggests
      that these peptides are important in up-regulating cell proliferation after Clara
      cell injury in the mouse.

PMID- 9250158
TI  - Analysis of p21Waf1/Cip1 expression in normal, premalignant, and malignant cells
      during the development of human lung adenocarcinoma.
AB  - Our studies suggested that adenocarcinoma of the peripheral lung mostly develops
      by several steps from atypical adenomatous hyperplasia through early
      adenocarcinoma to overt adenocarcinoma, and that some p53 abnormalities play an
      important role in this progression. In the present study, we examined by
      immunohistochemistry the expression of p53-inducible cyclin-dependent kinase
      inhibitor p21Waf1/Cip1 (p21) in the cells at various developmental stages of lung
      adenocarcinoma (32 lesions of adenomatous hyperplasia, 14 of early
      adenocarcinoma, 23 of well differentiated adenocarcinoma, and 17 of moderately or
      poorly differentiated adenocarcinoma) in comparison with 19 reactive
      proliferative lesions and analyzed the relationship between p53 and p21
      expression. Bronchioalveolar cells in the normal lung expressed very little or no
      p21 and no p53 expression. In not only reactive but also neoplastic lesions
      regardless of their developmental stage, the cells expressed p21 at various
      frequencies. The average labeling indices ranged from 5.4 to 13.8%, and there was
      no significant difference between any of these categories. The expression of p21,
      however, tended to be relatively low in moderately and poorly differentiated
      adenocarcinomas (5.5%) compared to well differentiated adenocarcinomas (12.2%),
      and high-level p21 expressors (10% < or = positive cells) were more frequent in
      the latter group (1 of 17 (6%) versus 3 of 23 (35%), P < 0.05), suggesting that
      p21 expression is affected by the degree of differentiation of the neoplastic
      cells. Although the correlation was positive between the expression of p21 and
      p53 in reactive lesions (r = 0.88; P < 0.001), none was found in neoplastic
      lesions at any step or grade (-0.12 < or = r < or = 0.26). These results
      indicated that p21 expression depends upon p53 expression in reactive lung cells,
      whereas p21 expression is at least in part independent of that of p53 from the
      earliest to the most fully developed step of lung adenocarcinoma tumorigenesis.
      We concluded that disruption of the p53-dependent cell cycle regulation is a very
      early event in the tumorigenesis of lung adenocarcinoma.

PMID- 9250159
TI  - Expression of P-cadherin identifies prostate-specific-antigen-negative cells in
      epithelial tissues of male sexual accessory organs and in prostatic carcinomas.
      Implications for prostate cancer biology.
AB  - Cadherins constitute a family of calcium-dependent cell-cell adhesion molecules
      the individual members of which are essential for the sorting of cells into
      tissues during development. In this study, we examined the expression of E
      cadherin, N-cadherin, and P-cadherin in tissues obtained from radical
      prostatectomies. Epithelial cells of prostatic glands, ejaculatory ducts, and
      seminal vesicles expressed E-cadherin but not N-cadherin. P-cadherin was
      expressed in epithelial cells of the seminal vesicles and ejaculatory ducts. In
      the prostate it was limited to the basal cells of prostatic acini, glands with
      basal cell hyperplasia, and atrophic glands denuded of the luminal cells. All P
      cadherin-positive cells were negative for prostatic-specific antigen. Prostatic
      cancers were mostly P-cadherin negative, but some tumors had P-cadherin-positive
      areas frequently located close to ejaculatory ducts and negative for prostatic
      specific antigen. The mutually exclusive expression of P-cadherin and prostatic
      specific antigen suggests that these proteins are involved in differential
      mechanisms of cell regulation in prostate cancer. P-cadherin may become a useful
      marker in the diagnosis and management of patients with prostate cancer and low
      levels of prostatic-specific antigen.

PMID- 9250161
TI  - Molecular analysis of T-cell clonality in ulcerative jejunitis and enteropathy
      associated T-cell lymphoma.
AB  - Ulcerative jejunitis (UJ) and enteropathy-associated T-cell lymphoma (EATL) are
      closely related conditions both associated with celiac disease. Benign-appearing
      inflammatory ulcers are seen in both, which has led to the suggestion that UJ is
      a manifestation of EATL. The aim of this study was to investigate this
      relationship using the polymerase chain reaction (PCR) to detect T-cell gene
      rearrangement. PCR amplification of the T-cell receptor gamma-chain gene was
      performed on DNA extracted from lymphoma, associated inflammatory ulcers, and
      intervening mucosa in six EATL cases and from ulcers and intervening mucosa of
      seven cases of UJ. In two of these cases, DNA from a subsequent lymphoma was also
      studied. The PCR products from the tumor and an ulcer from one EATL case, two
      ulcers from one case of UJ, and one ulcer and subsequent cutaneous lymphoma from
      one UJ case were sequenced. Twenty-five ulcers from twelve cases of Crohn's
      disease, twenty sections of normal bowel, and nine celiac biopsies were included
      as controls. A monoclonal T-cell population defined by a dominant band equal in
      size to that amplified from the lymphoma was identified in at least one ulcer
      from four informative EATL cases and from intervening mucosa in three.
      Monoclonality was demonstrated in at least one, and up to thirteen, ulcers from
      all seven cases of UJ, in intervening mucosa in five, and in the two subsequent
      lymphomas. Sequencing showed the same clone was present in the tumor and the
      ulcer in the EATL case, in two of three ulcers from the UJ case, and in an ulcer
      and subsequent cutaneous lymphoma in one UJ case. All Crohn's disease ulcers and
      all sections of normal bowel were polyclonal. One of nine celiac biopsies showed
      a dominant band. In conclusion, we have shown that T-cell monoclonality is a
      feature of the ulcers in both UJ and EATL and that the same clone is present in
      EATL and its associated inflammatory ulcers and in UJ and subsequently developing
      lymphoma.

PMID- 9250160
TI  - Tumor cell and connective tissue cell interactions in human colorectal
      adenocarcinoma. Transfer of platelet-derived growth factor-AB/BB to stromal
      cells.
AB  - Mechanisms underlying stimulation of platelet-derived growth factor (PDGF) beta
      receptors expressed on connective tissue cells in human colorectal adenocarcinoma
      were investigated in this study. PDGF-AB/BB, but not PDGF receptors, was
      expressed by tumor cells in situ, as well as in tumor cell isolates of low
      passage from human colorectal adenocarcinoma. In an experimental co-culture
      system, conditioned medium from tumor cells only marginally activated PDGF beta
      receptors expressed on fibroblasts. In contrast, co-culturing of the two cell
      types led to a marked PDGF beta-receptor activation. Functional PDGF-AB/BB was
      found to be associated with heparinase-I-sensitive components on the tumor cell
      surface. PDGF-AB/BB, isolated from heparinase-I-sensitive cell surface
      components, induced a marked activation of PDGF beta-receptors. Furthermore, co
      culturing tumor cells together with fibroblasts led to a sustained activation of
      PDGF beta-receptors expressed on fibroblasts. Double immunofluorescence staining
      of tissue sections from human colorectal adenocarcinoma, combined with computer
      aided image analysis, revealed that nonproliferating tumor cells were the
      predominant cellular source of PDGF-AB/BB in the tumor stroma. In addition, PDGF
      AB/BB-expressing tumor cells were found juxtapositioned to microvascular cells
      expressing activated PDGF beta-receptors. Confocal microscopy revealed a
      cytoplasmic and cell-membrane-associated expression of PDGF-AB/BB in tumor cells
      situated in the stroma. In contrast, epithelial cells situated in normal or
      tumorous acinar structures revealed only a cell-membrane-associated PDGF-AB/BB
      expression. The is vitro and in situ results demonstrate that tumor cells not
      only facilitate but also have the ability to modulate connective tissue cell
      responsiveness to PDGF-AB/BB in a paracrine fashion, through direct cell-cell
      interactions in human colorectal adenocarcinoma.

PMID- 9250162
TI  - Expression of collagenase-3 (matrix metalloproteinase-13) in squamous cell
      carcinomas of the head and neck.
AB  - Squamous cell carcinomas (SCCs) of the head and neck are malignant tumors with
      high capacity to invade and metastasize. We have examined expression of the new
      collagenase, collagenase-3 (MMP-13), in SCCs of the head and neck. MMP-13 mRNAs
      were detected in 22 of 29 SCC cell lines: in 14 of 15 primary SCC cell lines and
      in 8 of 14 SCC cell lines from recurrent tumors or metastases. MMP-13 mRNAs were
      expressed by all 6 cell lines from highly invasive primary tumors and in all 4
      cell lines from small aggressive tumors. Using in situ hybridization, MMP-13
      mRNAs were detected in 15 of 17 SCC tumor samples. In most tumors, MMP-13 was
      expressed by tumor cells at the invading front of the tumors, but in a subset of
      SCCs, MMP-13 mRNA was also expressed by stromal fibroblasts. No MMP-13 expression
      was detected in intact skin or oral mucosa. MMP-13 mRNA levels in SCC cells were
      enhanced by transforming growth factor-beta, tumor necrosis factor-alpha,
      transforming growth factor-alpha, and keratinocyte growth factor. Specific
      expression of MMP-13 by SCC cells in vitro and in vivo strongly suggests a role
      for MMP-13 in the high invasion capacity of SCC cells.

PMID- 9250164
TI  - Dysregulation of carcinoembryonic antigen group members CGM2, CD66a (biliary
      glycoprotein), and nonspecific cross-reacting antigen in colorectal carcinomas.
      Comparative analysis by northern blot and in situ hybridization.
AB  - Genes coding for CD66a (biliary glycoprotein), carcinoembryonic antigen (CEA)
      group member 2 (CGM2), and nonspecific cross-reacting antigen (NCA) are members
      of the human CEA gene subgroup. We investigated a series of 11 colorectal
      carcinomas by Northern blot and isotopic in situ hybridization (ISH),
      demonstrating underexpression of CD66a and CGM2 in the majority of the carcinomas
      as compared with the normal mucosa, whereas NCA was overexpressed. ISH for CD66a
      and CGM2 mRNA revealed that large areas of the carcinomas remained without or
      with only faint hybridization signals. However, in every carcinoma, at least some
      positive foci were observed, indicating remaining cell populations that actively
      transcribe CD66a and CGM2. In contrast, ISH for NCA displayed strong and
      extensive autoradiographic signals. By analysis of step sections, foci of CD66a
      and CGM2 expression were shown to co-localize. Furthermore, these foci contained
      relatively few nuclei immunohistochemically positive for the proliferation
      associated nuclear antigen Ki-67. Our data indicate a dysregulation of the three
      genes possibly with a common transcriptional control for CD66a and CGM2 and a
      different control for NCA. The focal expression of CD66a and CGM2 could be
      interpreted as due to a focal, incomplete, and abortive differentiation or,
      alternatively, as a consequence of genetic heterogeneity with foci of slow
      proliferating subclones.

PMID- 9250163
TI  - Transforming growth factor-beta, transforming growth factor-beta receptor II, and
      p27Kip1 expression in nontumorous and neoplastic human pituitaries.
AB  - Transforming growth factor (TGF)-beta has been implicated in the regulation of
      normal and neoplastic anterior pituitary cell function. TGF-beta regulates the
      expression of various proteins, including p27Kip1 (p27), a cell cycle inhibitory
      protein. We examined TGF-beta, TGF-beta type II receptor (TGF-beta-RII), and p27
      expression in normal pituitaries, pituitary adenomas, and carcinomas to analyze
      the possible roles of these proteins in pituitary tumorigenesis. Normal
      pituitary, pituitary adenomas, and pituitary carcinomas all expressed TGF-beta
      and TGF-beta-RII immunoreactivity. Reverse transcription polymerase chain
      reaction analysis showed TGF-beta 1, -beta 2, and -beta 3 isoforms and TGF-beta
      RII in normal pituitaries and pituitary adenomas. Pituitary adenomas cells
      cultured for 7 days in defined media showed a biphasic response to TGF-beta with
      significant inhibition of follicle-stimulating hormone secretion at higher
      concentrations (10(-9) mol/L) and stimulation of follicle-stimulating hormone
      secretion at lower concentrations (10(-13) mol/L) of TGF-beta 1 in gonadotroph
      adenomas. Immunohistochemical analysis for p27 protein expression showed the
      highest levels in nontumorous pituitaries with decreased immunoreactivity in
      adenomas and carcinomas. When nontumorous pituitaries and various adenomas were
      analyzed for p27 and specific hormone production, growth hormone, luteinizing
      hormone, and thyroid-stimulating hormone cells and tumors had the highest
      percentages of cells expressing p27, whereas adrenocorticotrophic hormone cells
      and tumors had the lowest percentages. Immunoblotting analysis showed that
      adrenocorticotrophic hormone adenomas also had the lowest levels of p27 protein.
      Semiquantitative reverse transcription polymerase chain reaction and Northern
      hybridization analysis did not show significant differences in p27 mRNA
      expression in the various types of adenomas or in nontumorous pituitaries. In
      situ hybridization for p27 mRNA showed similar distributions of the gene product
      in nontumorous pituitaries, pituitary adenomas, and carcinomas. These results
      indicate that TGF-beta and TGF-beta-RII are widely expressed in nontumorous
      pituitaries and in pituitary neoplasms and that TGF-beta 1 regulates pituitary
      hormone secretion. The levels of the TGF-beta-regulated protein p27 decreases in
      the progression of normal to neoplastic pituitaries. In contrast, the mRNA levels
      of p27 remained relatively constant in nontumorous pituitaries, pituitary
      adenomas, and carcinomas, indicating that p27 protein levels in adenomas and
      carcinomas are regulated by translational and post-translational mechanisms.

PMID- 9250165
TI  - Macrophage apoptosis in rat crescentic glomerulonephritis.
AB  - The fate of macrophages at the site of inflammation is unknown. We investigated
      this question in a macrophage-mediated model of crescentic glomerulonephritis in
      which macrophage accumulation is relatively stable despite the presence of high
      levels of local macrophage proliferation. Accelerated anti-glomerular basement
      membrane glomerulonephritis was induced in groups of six rats that were killed on
      day 1, 7, 14, or 21. Macrophage apoptosis was demonstrated in kidney sections by
      three methods: in situ terminal deoxyribonucleotide transferase (TdT)-mediated
      dUTP nick end labeling (TUNEL) combined with ED1 antibody immunostaining of
      macrophages, ED1 immunostaining combined with classical nuclear morphology, and
      electron microscopy. Substantial macrophage apoptosis became evident on day 14 of
      the disease, following the appearance of high levels of macrophage proliferation.
      The parallel relationship between proliferation and apoptosis is the likely
      explanation for the stabilization of macrophage numbers within the inflamed
      kidney. A striking feature was that macrophage proliferation and apoptosis was
      largely restricted to areas of focal damage, such as in the development of
      glomerular crescents. Increasing levels of macrophage proliferation and apoptosis
      were evident as crescents developed from a cellular to a fibrocellular phenotype,
      with a dramatic reduction in both of these processes in the progression to a
      fibrotic phenotype, suggesting an important role for macrophage apoptosis in the
      resolution of fibrocellular crescents to an acellular fibrotic structure. In
      conclusion, this study has identified apoptosis as an important mechanism
      counterbalancing local proliferation in the regulation of macrophage accumulation
      at sites of inflammation. Indeed, apoptosis may be a central regulator of the
      progression and resolution of macrophage-mediated tissue injury.

PMID- 9250166
TI  - Role of complement in acute tubulointerstitial injury of rats with
      aminonucleoside nephrosis.
AB  - The present work was designed to elucidate the in vivo role of complement in the
      proteinuria-associated tubulointerstitial injury. Rats were intravenously
      injected with puromycin aminonucleoside, and massive proteinuria was observed
      within 5 days. Prominent tubulointerstitial injury characterized by proximal
      tubular degeneration, tubular dilatation, and leukocyte infiltration were
      observed 7 days after injection. C3 and C5b-9 were observed in the luminal side
      of proximal tubular cells. Renal function, assessed by inulin and para
      aminohippurate clearance, was significantly decreased. To-assess the role of
      complement in this model, rats were injected with either cobra venom factor or
      soluble recombinant human complement receptor type 1 starting at day 3. These
      manipulations significantly improved tubulointerstitial pathology and para
      aminohippurate clearance without affecting the degree of proteinuria. Deposition
      of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by
      cobra venom factor. In rats treated with soluble complement receptor, C3 was
      still detected in the tubules, but deposition of C5b-9 was not observed. Soluble
      complement receptor was detected at the site of C3 deposition and in the urine.
      These data strongly suggest that complement plays a pivotal role in proteinuria
      associated tubulointerstitial injury and that systemic complement depletion or
      inhibition of complement in the tubular lumen may diminish the tubulointerstitial
      damage.

PMID- 9250167
TI  - Pattern of superoxide dismutase enzymatic activity and RNA changes in rat heart
      ventricles after myocardial infarction.
AB  - A multiplex reverse transcription polymerase chain reaction assay was designed to
      measure manganese superoxide dismutase (MnSOD) and CuZnSOD mRNAs in the left and
      right ventricles of rat hearts after myocardial infarction induced by occlusion
      of the left coronary artery. These data were compared with changes in enzymatic
      activities. In the left ventricle, Mn-SOD RNA increased significantly at 6 hours,
      peaked at 12 hours (490 +/- 38 arbitrary units), and progressively decreased (127
      +/- 21 arbitrary units at 48 hours). In contrast, there was a steady accumulation
      of transcripts in the right ventricle up to 48 hours. In both ventricles, the
      changes in the MnSOD mRNA and protein content were not associated with
      proportional variations in enzymatic activity. There was no characteristic
      alteration of the CuZnSOD system in either ventricle over the 48-hour period.
      These results demonstrate that infarction selectively activates the MnSOD gene in
      the viable myocardium of both ventricles. They suggest that MnSOD may be involved
      in the adaptive response of myocytes to the overloading stress.

PMID- 9250169
TI  - Evidence for clonal origin of neoplastic neuronal and glial cells in
      gangliogliomas.
AB  - Gangliogliomas are rare tumors of the central nervous system that account for
      approximately 1% of all brain tumors. Histologically, gangliogliomas are composed
      of intimately admixed glial and neuronal components, the pathological origins of
      which remain to be characterized. Clonal analysis through examination of the
      pattern of the X chromosome inactivation allows one to distinguish monoclonal
      differentiation of a genetically abnormal progenitor cell from parallel, but
      independent, clonal expansion of two different cell types during tumorigenesis in
      biphasic neoplasms, such as gangliogliomas. In the present study, we investigated
      the clonality of eight gangliogliomas from female patients using both methylation
      and transcription-based clonality assays at the androgen receptor locus (HUMARA)
      on the X chromosome. Among tumors from seven patients who were heterozygous at
      the HUMARA locus, five were identified as monoclonal with the methylation-based
      clonality assay, and the results were confirmed by the transcription-based
      method, whereas two were shown to be polyclonal by the methylation-based
      clonality assay but monoclonal by transcription-based clonality analysis. We
      conclude that the predominant cell types in most gangliogliomas are monoclonal in
      origin and derive from a common precursor cell that subsequently differentiates
      to form neoplastic glial and neuronal elements.

PMID- 9250168
TI  - Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor
      and tumor necrosis factor-alpha.
AB  - We evaluated the role of an endogenous production of nitric oxide (NO) in the in
      vitro migration of endothelial cells and in the in vivo angiogenic response
      elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF),
      and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega
      nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented
      chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic
      activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor
      antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME
      or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which
      Matrigel was used as a vehicle for the delivery of mediators. In this model, the
      angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not
      by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME
      or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These
      results suggest that NO mediates the angiogenesis induced by PAF as well as that
      induced by TNF, which is dependent on the production of PAF. In contrast, the
      angiogenic effect of bFGF appears to be both PAF and NO independent.

PMID- 9250170
TI  - Intestinal stem cell division and genetic diversity. A computer and experimental
      analysis.
AB  - Somatic mutations are expected to arise with age. This process is accelerated in
      mice lacking the DNA mismatch repair gene Pms2. The distributions of
      microsatellite alleles present in small patches of normal Pms2 -/- intestines
      revealed a general increase in genetic diversity or the number of mutations with
      age. However, the patterns were complex with different distributions and
      variances present within a single mouse. Computer simulations indicate that the
      experimental data are consistent with mutation rates between 0.0020 and 0.0025
      mutations per division, nonrandom cell death, and an effective population size of
      20 or fewer cells. Small numbers of cells exacerbate the random accumulation of
      mutations expected of a stochastic mutation process. The computer simulations and
      experimental data are consistent with known patterns of intestinal development
      and renewal by small numbers of stem cells and demonstrate relatively high
      mutation rates in histologically normal epithelium. These findings provide
      background for the analysis of microsatellite mutations in normal and tumor
      tissue lacking mismatch repair and further support the hypothesis that
      microsatellite loci can function as molecular tumor clocks.

PMID- 9250171
TI  - X inactivation in human testicular tumors. XIST expression and androgen receptor
      methylation status.
AB  - In female mammalian cells, inactivation of one of the X chromosomes compensates
      the increased dosage of X-linked genes as compared with their male counterparts.
      This process is initiated by the X-inactive specific transcripts of the xist/XIST
      gene in cis, resulting in methylation of specific sites of genes to be silenced.
      However, in male germ cells, X inactivation is established by xist/XIST
      expression only. We investigated the X inactivation pattern in human testicular
      tumors of different histogenesis by analysis of XIST expression and methylation
      of the androgen receptor gene. XIST was expressed only in tumors derived from the
      germ cell lineage with supernumerical X chromosomes: seminomas, nonseminomas, and
      spermatocytic seminomas. Although low expression was present in testicular
      parenchyma with spermatogenesis, XIST was expressed at a higher level in
      parenchyma with carcinoma in situ, the precursor lesion of seminomas and
      nonseminomas. Despite the consistent expression of XIST in germ-cell-derived
      tumors with gain of X chromosomes, methylation of the androgen receptor gene was
      present in all differentiated but only in a proportion of the undifferentiated
      nonseminomas. This differential pattern of methylation was also found in a number
      of representative cell lines. Our data indicate that the counting mechanism
      resulting in X inactivation is functional in testicular cancers of different
      histogenesis. Moreover, the differentiation-dependent pattern of X inactivation
      as reported during normal development in the case of multiple X chromosomes by
      methylation is retained in these tumors. We conclude therefore that X
      inactivation allows the excessive gain of X chromosomes found in germ-cell
      derived tumors of the adult testis. In addition, this offers an interesting model
      to study the fundamental mechanisms of these processes.

PMID- 9250172
TI  - Rat stem cells developing in irradiated SCID mice fail to become tolerized and
      cause lethal graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is prominent in irradiated hosts given whole
      allogeneic bone marrow cells but is generally undetectable when T-depleted stem
      cells are transferred; under these conditions, the mature T cells arising from
      the donor stem cells become tolerant to host antigens and fall to cause GVHD. We
      show here that a radically different situation can occur when hosts are
      reconstituted with xenogeneic stem cells. When lightly irradiated, adult C.B-17
      SCID mice injected with Lewis rat fetal liver (FL) cells show near-total
      repopulation with rat-derived lymphohemopoietic cells, including T and B cells.
      However, in marked contrast to chimeras prepared with allogeneic mouse FL cells,
      rat FL-->SCID chimeras develop severe and often lethal chronic GVHD. In these rat
      ->mouse chimeras, the rat T cells show limited tolerance to host mouse antigens
      as determined by various parameters including mixed lymphocyte reaction and
      cytotoxic T lymphocyte assays in vitro, adoptive transfer of T cells to secondary
      SCID hosts, and the lack of V beta deletion to endogenous host mtv antigens. GVHD
      in irradiated rat-->SCID chimeras is most prominent with Lewis FL but also
      applies to Fisher 344 and Wistar Furth FL cells. The failure of newly formed rat
      T cells in rat-->SCID chimeras to become fully tolerant to host mouse antigens
      appears to be due to depletion of host antigen-presenting cells by irradiation.
      Thus, rat-->SCID chimeras generated by transplanting rat FL cells into
      unirradiated neonatal SCID mice fail to develop GVHD, and the rat T cells display
      self-tolerance. As allogeneic H-2-different mouse FL-->irradiated SCID chimeras
      display strong self-tolerance, presumably through recognition of host antigens on
      thymic epithelial cells, the implication is that mouse thymic epithelial cells
      are tolerogenic only for mouse and not for rat immature T cells.

PMID- 9250173
TI  - Presenilin-1 is associated with Alzheimer's disease amyloid.
AB  - Mutations in presenilin (PS)-1 and -2, located on chromosome 14 and 1
      respectively, are the major association with early-onset familial Alzheimer's
      disease (FAD). FAD has also been linked to mutations in the amyloid beta
      precursor protein (beta PP), and the presence of the apolipoprotein E4 allele is
      a risk factor for late-onset AD. The role of PS in FAD and in sporadic AD is
      unclear. We previously reported the presence of a PS-1 carboxyl-terminal epitope
      in neuritic plaques (Wisniewski T, Palha JA, Ghiso J, Frangione B: S182 protein
      in Alzheimer's disease neuritic plaques. Lancet 1995, 346:1366). In the present
      study, we examined a number of biochemically different cerebral and systemic
      amyloidoses, finding the PS-1 carboxy epitope only in association with amyloid
      beta (A beta) lesions. We confirm the presence of this epitope ultrastructurally
      in neuritic plaques. In addition, biochemical and amino acid sequence data are
      presented for an association of the 18-kd carboxy fragment of PS-1 with neuritic
      plaques with a start at residue 300. Three of the proteins with linkage to AD
      have now been found as components of neuritic plaques. It remains to be
      determined whether all of these proteins are involved in the same or different
      pathological pathway(s) and which of these proteins is the most important for the
      common, late-onset form of AD.

PMID- 9250174
TI  - Timed appearance of lymphocytic choriomeningitis virus after gastric inoculation
      of mice.
AB  - Arenaviruses present an emerging health threat in agrarian areas of Africa and
      South America; however, the natural routes of arenaviral infections are not
      clearly understood. Our previous studies with lymphocytic choriomeningitis virus
      (LCMV), the prototype arenavirus, implicate oral and intragastric routes as
      natural routes of infection. Our studies raised many questions about the primary
      site of infection and the route of dissemination after gastric infection. In this
      report, we use in situ hybridization to detect LCMV in various organs at
      different time points (0 to 96 hours). After gastric inoculation, the gastric
      mucosa is the initial site of viral infection, followed by infection of the
      spleen and liver, then ileum and last, lung, kidney, brain, and esophagus.
      Furthermore, our observations suggest that virus is disseminated lymphatically
      rather than by a hematogenous route. Infectious center assays using mononuclear
      cells from stomach, blood, and spleen of mice infected by the gastric route
      confirmed active infection with LCMV and the presence of mononuclear cells
      producing infectious virus in these tissues. This is the first identification of
      gastric epithelia as a primary site of virus infection.

PMID- 9250175
TI  - A curious stopping rule from Hoechst Marion Roussel.

PMID- 9250176
TI  - CHART for non-small-cell lung cancer--promises and limitations.

PMID- 9250177
TI  - Making DOTS succeed. Directly Observed Treatment, Short Course.

PMID- 9250178
TI  - NIDDM and breastfeeding.

PMID- 9250179
TI  - Prevention of hearing loss from meningitis.

PMID- 9250180
TI  - Genes, familial enuresis, and clinical management.

PMID- 9250182
TI  - Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional
      radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART
      Steering Committee.
AB  - BACKGROUND: Human tumour cells can proliferate rapidly, and giving radiotherapy
      in many small fractions may reduce long-term normal-tissue morbidity. In response
      to these observations, we developed the CHART (continuous hyperfractionated
      accelerated radiotherapy) regimen, which uses thirty-six small fractions of 1.5
      Gy given three times per day, to give 54 Gy in only 12 consecutive days. We
      report the long-term follow-up of a trial of CHART versus conventional
      radiotherapy in patients with locally advanced non-small-cell lung cancer
      (NSCLC). METHODS: 563 patients were entered by thirteen centres between April,
      1990, and March, 1995. We included patients with NSCLC localised to the chest
      with a performance status of 0 or 1 in whom radical radiotherapy was chosen as
      the definitive management. Patients were randomly allocated in a 3:2 ratio to
      CHART or conventional radiotherapy. The latter was thirty fractions of 2 Gy to a
      total dose of 60 Gy in 6 weeks. RESULTS: The groups were well matched for
      possible prognostic factors. Overall there was a 24% reduction in the relative
      risk of death, which is equivalent to an absolute improvement in 2-year survival
      of 9% from 20% to 29% (p = 0.004, 95% CI 0.63-0.92). Subgroup analyses
      (predefined) suggest that the largest benefit occurred in patients with squamous
      cell carcinomas (82% of the cases), in whom there was a 34% reduction in the
      relative risk of death (an absolute improvement at 2 years of 14% from 19% to
      33%). During the first 3 months, severe dysphagia occurred more often in the
      CHART group than in the group on conventional radiotherapy (19 vs 3%). Otherwise,
      there were no important differences in short-term or long-term morbidity.
      INTERPRETATION: CHART compared with conventional radiotherapy gave a significant
      improvement in survival of patients with NSCLC. Further improvement may be
      achieved with dose escalation in conformal radiotherapy, by the addition of
      cytotoxic chemotherapy, and by hypoxic cell radiosensitisation.

PMID- 9250183
TI  - Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima
      Indians.
AB  - BACKGROUND: Early exposure to cow's milk has been implicated in the occurrence of
      insulin-dependent diabetes mellitus but there is little information about infant
      feeding practices and subsequent non-insulin-dependent diabetes mellitus (NIDDM).
      We examined the association between breastfeeding and NIDDM in a population with
      a high prevalence of this disorder, the Pima Indians. METHODS: Glucose-tolerance
      status was obtained from a 75 g oral glucose-tolerance test. A standard
      questionnaire given to mothers was used to classify infant-feeding practices for
      the first 2 months of life into three groups; exclusively breastfed, some
      breastfeeding, or exclusively bottlefed. The association between the three infant
      feeding groups and NIDDM was analysed by multiple logistic regression. FINDINGS:
      Data were available for 720 Pima Indians aged between 10 and 39 years. 325 people
      who were exclusively bottlefed had significantly higher age-adjusted and sex
      adjusted mean relative weights (146%) than 144 people who were exclusively
      breastfed (140%) or 251 people who had some breastfeeding (139%) (p = 0.019).
      People who were exclusively breastfed had significantly lower rates of NIDDM than
      those who were exclusively bottlefed in all age-groups (age 10-19, 0 of 56 vs 6
      [3.6%] of 165; age 20-29, 5 [8.6%] of 58 vs 17 [14.7%] of 116]; age 30-39, 6
      [20.0%] of 30 vs 13 [29.6%] of 44). The odds ratio for NIDDM in exclusively
      breastfed people, compared with those exclusively bottlefed, was 0.41 (95% CI
      0.18-0.93) adjusted for age, sex, birthdate, parental diabetes, and birthweight.
      INTERPRETATION: Exclusive breastfeeding for the first 2 months of life is
      associated with a significantly lower rate of NIDDM in Pima indians. The increase
      in prevalence of diabetes in some populations may be due to the concomitant
      decrease in breastfeeding.

PMID- 9250184
TI  - Control of tuberculosis by community health workers in Bangladesh.
AB  - BACKGROUND: Tuberculosis remains a major public-health problem in Bangladesh,
      despite national efforts to improve case identification and treatment compliance.
      In 1984, BRAC (formerly the Bangladesh Rural Advancement Committee), a national,
      non-governmental organisation, began an experimental tuberculosis-control
      programme in one thana (subdistrict). Community health workers screened villagers
      for chronic cough and collected sputum samples for acid-fast bacillus (AFB)
      microscopy (phase one). Positive patients received 12 months of directly observed
      therapy. Phase two (1992-94) included another nine thanas and, in phase three
      (1995), eight more thanas were included. From 1995, the treatment was an 8-month
      oral regimen. METHODS: In 1995-96, we analysed all programme data from 1992 to
      1995. First we analysed phases two (12-month therapy) and three (8-month therapy)
      separately for proportion cured, died, treatment, failed, defaulted, migrated,
      and referred. Second, we did a cross-sectional survey of tuberculosis cases in
      more than 9000 randomly selected households in two phase-two thanas and one non
      programme thana, and analysed the follow-up of all patients treated in the
      programme thanas. FINDINGS: In the phase-two analysis, 3497 (90%) of 3886 cases
      identified had accepted 12-month treatment. In phase three, all of 1741
      identified cases accepted the 8-month regimen. 2833 (81.0%) and 1496 (85.9%) in
      phases two and three, respectively, were cured; 336 (9.6%) and 133 (7.6%) died.
      The relapse rate 2 or more years after treatment was discontinued was higher than
      the early relapse rate. The drop-out rate was 3.1%. In the cross-sectional
      survey, the prevalence of tuberculosis in the two programme thanas was half of
      that in the comparison thana, where only government services were available (0.07
      vs 0.15 per 100 [corrected]). INTERPRETATION: The BRAC tuberculosis-control
      programme has successfully achieved high rates of case detection and treatment
      compliance, with a cure rate of at least 85% and a drop-out rate of 3.1%. The
      prevalence survey suggested that at least half of all existing cases had been
      detected by the programme.

PMID- 9250185
TI  - Outbreak of toxoplasmosis associated with municipal drinking water. The BC
      Toxoplasma Investigation Team.
AB  - BACKGROUND: Outbreaks of toxoplasmosis are recognised infrequently. In March,
      1995, a sudden increase of serologically diagnosed cases of acute toxoplasmosis
      was noted in the Greater Victoria area of British Columbia, Canada. Concurrently,
      but independently, seven cases of acute toxoplasma retinitis were diagnosed
      against a background of no cases in the previous 5 years. METHODS: Cases were
      defined by serological testing, clinical presentation, and residence in Greater
      Victoria. A screening programme for women who were or had been pregnant was
      started. Geographical mapping of cases, and case-control studies of symptomatic
      cases and of women enrolled in the screening programme were done. FINDINGS: 100
      individuals aged 6 to 83 years met the definition for an acute, outbreak-related
      case. 94 resided in Greater Victoria and six had visited it; 19 had retinitis, 51
      had lymphadenopathy, four others had symptoms consistent with toxoplasmosis,
      seven had other symptoms, 18 were symptom-free, and one would not provide
      information. 36 (0.9%) of 3812 screened pregnant and postnatal women were cases.
      Excess cases were not detected outside Greater Victoria and no conventional
      source of toxoplasmosis was implicated. Mapping studies of cases and of the
      screened women, and both case-control studies showed significant associations
      between acute infection and residence in the distribution system of one reservoir
      supplying water to Greater Victoria (ORs or RRs: 3.53, 3.05, 8.27, and 5.42,
      respectively). The epidemic curve appeared bimodal, with peaks in December, 1994,
      and March, 1995, that were preceded by increased rainfall and turbidity in the
      implicated reservoir. INTERPRETATION: A municipal water system that uses
      unfiltered, chloraminated surface water was the likely source of this large
      community-wide outbreak of toxoplasmosis.

PMID- 9250186
TI  - Nerve ingrowth into diseased intervertebral disc in chronic back pain.
AB  - BACKGROUND: In the healthy back only the outer third of the annulus fibrosus of
      the intervertebral disc is innervated. Nerve ingrowth deeper into diseased
      intervertebral disc has been reported, but how common this feature is and whether
      it is associated with chronic pain are unknown. We examined nerve growth into the
      intervertebral disc in the pathogenesis of chronic low back pain. METHODS: We
      collected 46 samples of intervertebral discs from 38 patients during spinal
      fusion for chronic back pain. 30 samples were from pain levels clinically
      established by discography and 16 samples were from adjacent vertebral levels
      with no pain. We obtained 34 control samples of intervertebral disc from
      previously healthy individuals with normal histology within 8 h of recorded
      death. We used standard immunohistochemical techniques to test for a general
      nerve marker, a nociceptive neurotransmitter (substance P), and a protein
      expressed during axonogenesis (growth-associated protein 43 [GAP43]). FINDINGS:
      We identified nerve fibres in the outer third of the annulus fibrosus in 48 (60%)
      of the 80 samples of intervertebral discs. Nerves were restricted to the outer or
      middle third of the annulus fibrosus in the 34 control samples. Among the
      patients with chronic low back pain, nerves extended into the inner third of the
      annulus fibrosus and into the nucleus pulposus in 21 (46%) and ten (22%) samples,
      respectively. Nerves usually accompanied blood vessels, but in 14 of the samples
      from back-pain patients, isolated nerve fibres were seen in the discal matrix.
      Both types of nerve fibres expressed substance P, but only non-vessel-associated
      fibres expressed GAP43. Deep nerve ingrowth into the inner third of the annulus
      fibrosus, the nucleus pulposus, or both was seen in four (25%) of 16 biopsy
      samples from non-pain levels and in 17 (57%) samples from pain levels. Of the 16
      paired samples from both pain and non-pain levels, five pain-level samples and
      one non-pain-level sample showed deep nerve ingrowth. INTERPRETATION: Our finding
      of isolated nerve fibres that express substance P deep within diseased
      intervertebral discs and their association with pain suggests an important role
      for nerve growth into the intervertebral disc in the pathogenesis of chronic low
      back pain.

PMID- 9250187
TI  - A blinding headache.

PMID- 9250188
TI  - Ambiguous genitalia in infant exposed to tamoxifen in utero.

PMID- 9250189
TI  - Efficacy of troglitazone measured by insulin resistance index.

PMID- 9250190
TI  - Adult night terrors and paroxetine.

PMID- 9250192
TI  - Birth of infant after transfer of anucleate donor oocyte cytoplasm into recipient
      eggs.

PMID- 9250191
TI  - Does blinding of readers affect the results of meta-analyses? University of
      Pennsylvania Meta-analysis Blinding Study Group.

PMID- 9250193
TI  - Multidisciplinary breath-odour clinic.

PMID- 9250194
TI  - Is the neuropathology of new variant Creutzfeldt-Jakob disease and kuru similar?

PMID- 9250195
TI  - Type of prion protein in UK farmers with Creutzfeldt-Jakob disease.

PMID- 9250196
TI  - New AIDS drugs affect US state assistance.

PMID- 9250197
TI  - Diabetic eye disease.

PMID- 9250198
TI  - W H R Rivers: portrait of a great physician in Pat Barker's Regeneration trilogy.

PMID- 9250199
TI  - Epidemics of syphilis in the Russian Federation: trends, origins, and priorities
      for control.
AB  - After continuous decline throughout the 1980s, surveillance-defined estimates of
      the incidence of syphilis in Russia have shown a rapid and substantial increase
      during the 1990s. The reasons for this epidemic are unclear, but must be sought
      among changes both in sexual behaviour and in the patterns of provision, use, and
      effectiveness of diagnostic, treatment, and contact tracing services. High
      incidence of sexually transmitted disease causes correspondingly high levels of
      morbidity and suffering as well as significant health-care and other economic
      costs. Our current understanding suggests that the transmissibility of HIV is
      increased by infection with sexually transmitted disease. The syphilis epidemic
      together with changes in sexual behaviour, increased travel and migration, and
      rapid increases in injecting drug use may create the conditions for an epidemic
      of sexually acquired HIV infection in Russia that substantially outstrips those
      encountered in most Western European countries.

PMID- 9250200
TI  - Early closure of European Pimagedine trial. Steering Committee. Safety Committee.

PMID- 9250201
TI  - Deaths associated with ivermectin for scabies.

PMID- 9250202
TI  - Deaths associated with ivermectin for scabies.

PMID- 9250203
TI  - Deaths associated with ivermectin for scabies.

PMID- 9250204
TI  - Diagnosis of subarachnoid haemorrhage.

PMID- 9250205
TI  - Transfusional risk of HHV-8 infection.

PMID- 9250206
TI  - Accuracy of DINAMAP monitors.

PMID- 9250207
TI  - Hepatitis B and health-care workers.

PMID- 9250208
TI  - Hepatitis B and health care workers.

PMID- 9250209
TI  - High sequence homology of the PrP gene in mule deer and Rocky Mountain elk.

PMID- 9250210
TI  - Oral submucous fibrosis and copper.

PMID- 9250211
TI  - Placental vascular remodelling.

PMID- 9250212
TI  - Late postnatal transmission of HIV-1 and early weaning.

PMID- 9250213
TI  - Management of enuresis.

PMID- 9250214
TI  - Haemophilus influenzae type b vaccination.

PMID- 9250215
TI  - Haemophilus influenzae type b vaccination.

PMID- 9250217
TI  - Places of worship and health education.

PMID- 9250216
TI  - The Islamic view in genetic preventive procedures.

PMID- 9250218
TI  - Bacterial threats to new hospitals.

PMID- 9250219
TI  - False chloroquine resistance in Africa.

PMID- 9250220
TI  - Tuberculosis in elephants.

PMID- 9250221
TI  - The moribund autopsy. DNR or CPR?

PMID- 9250222
TI  - Physician-assisted suicide. Compassionate care or brave New World?

PMID- 9250223
TI  - Oregon's physician-assisted suicide law. An alternative positive viewpoint.

PMID- 9250224
TI  - Case of the month.

PMID- 9250225
TI  - Glucocorticoidlike activity of megestrol. A summary of Food and Drug
      Administration experience and a review of the literature.
AB  - Sporadic single case reports linking glucocorticoidlike activity to megestrol
      acetate have been reported in the literature. These findings have important
      implications for patient care. Adverse drug experience reports to the US Food and
      Drug Administration from 1984 through 1996 and a MEDLINE search of the literature
      from 1984 through 1996 provided the case reports. Five cases of Cushing syndrome,
      12 cases of new-onset diabetes, and 16 cases of adrenal insufficiency were
      identified in association with megestrol therapy. Twelve cases in which
      preexisting diabetes was exacerbated and 17 cases of possible adrenal
      insufficiency were identified. Therapy with megestrol can result in clinical
      manifestations of glucocorticoidlike activity, including Cushing syndrome,
      diabetes, and adrenal insufficiency. Clinicians need to be aware of this
      association as these complications can be life-threatening if not recognized.

PMID- 9250226
TI  - The effect of patient and provider reminders on mammography and Papanicolaou
      smear screening in a large health maintenance organization.
AB  - BACKGROUND: We evaluated the effectiveness of 2 reminder interventions to
      increase the use of screening mammograms and Papanicolaou (Pap) smears among
      female members of a large health maintenance organization. METHODS: Seven
      thousand seventy-seven female health maintenance organization members (aged 50-74
      years with no prior mammogram in the previous 30 months or aged 20-64 years with
      no prior Pap smear in the previous 36 months) were randomized to receive one of
      the following: a letter inviting them to make an appointment for a mammogram or a
      Pap smear; in addition to the letter, a reminder manually placed in the patient's
      medical chart alerting providers of that member's need for screening; or their
      usual care. RESULTS: Compared with women who did not receive the reminder letter,
      women who did receive the letter were more likely to obtain mammograms (16.0% vs
      25.5%, respectively; P < .001) or Pap smears (9.1% vs 19.5%, respectively; P <
      .001) in the 6 months following their entry into the study. Compared with women
      who received only the reminder letter, women who received a reminder letter and
      had a reminder placed in their medical chart were more likely to obtain
      mammograms (26.5% vs 30.9%, respectively; P = .02) and marginally more likely to
      receive Pap smears (19.5% vs 22.8%, respectively; P = .04). CONCLUSIONS: We
      recommend the use of patient reminder letters as a first step in a mammography or
      Pap smear screening outreach program. Further research is needed to evaluate a
      cost-effective provider reminder system and additional outreach strategies
      directed to women who do not use health care services.

PMID- 9250227
TI  - Deep vein thrombosis and pulmonary embolism in the general population. 'The Study
      of Men Born in 1913'.
AB  - BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common
      public health problems. Still, little is known about the epidemiology and the
      natural history of venous thromboembolism. METHODS: In the Study of Men Born in
      1913, 855 men were followed up prospectively from the age of 50 years to the age
      of 80 years. Several cross-sectional samples, also of men born in 1913, were
      studied at the ages of 50, 54, 60, 67, 75, and 80 years. Objective methods were
      used to ascertain a diagnosis of DVT or PE, and all were confirmed by hospital
      records or autopsy reports. The follow-up rate in the longitudinal study was
      98.2%. RESULTS: In the longitudinal study, the incidence of DVT was 182 per
      100,000 observation-years. Corresponding incidence rates were 98 for nonfatal PE,
      107 for fatal PE, and 387 for all thromboembolic events. The cumulative
      probability for a venous thromboembolic event at different ages was estimated to
      be 0.5% by the age of 50 years and 10.7% by the age of 80 years. In the cross
      sectional studies, a history of confirmed venous thromboembolism was found in
      0.5% of the men at age 50 years, 0.9% at age 54 years, 1.3% at age 60 years, 2.0%
      at age 67 years, 4.5% at age 75 years, and 3.8% at age 80 years. CONCLUSIONS: The
      results indicate a high incidence of DVT and PE in the general population. The
      incidence of thromboembolic events increases with age. The rate of fatal PE seems
      to be higher than estimated before, and PE constitutes almost 5% of all deaths
      during follow-up.

PMID- 9250228
TI  - Gallstone size and risk of pancreatitis.
AB  - BACKGROUND: The treatment of patients with gallstones who have suffered a first
      episode of acute biliary pain is controversial. Recent guidelines suggest that
      such patients may choose to observe the "pattern" of their pain over time before
      deciding about therapy. OBJECTIVE: To determine clinical factors that would
      identify patients at high risk for 2 important complications: acute biliary
      pancreatitis and acute cholecystitis. METHODS: We collected sociodemographic and
      clinical data on patients undergoing cholecystectomy after acute biliary
      pancreatitis, acute cholecystitis, or uncomplicated biliary pain. The physical
      characteristics of gallstones recovered at surgery were also recorded. Patients
      with pancreatitis and patients with cholecystitis were compared with patients
      with uncomplicated pain. RESULTS: In univariate analyses, patients with acute
      pancreatitis were significantly more likely to have at least 1 gallstone smaller
      than 5 mm in diameter, 20 or more gallstones, gallstones described as mulberry
      shaped, and a lower total gallstone weight than patients with uncomplicated pain.
      Pancreatitis was unrelated to patient age, sex, race or ethnicity, use of alcohol
      or tobacco, or clinical comorbidity. In a logistic regression model, acute
      pancreatitis was associated with a stone diameter of less than 5 mm (odds ratio,
      4.51; P = .007) and with mulberry-shaped gallstones (odds ratio, 2.25; P = .04).
      No sociodemographic, clinical, or gallstone characteristics were consistently
      associated with acute cholecystitis. CONCLUSIONS: Patients with at least 1
      gallstone smaller than 5 mm in diameter have a more than 4-fold increased risk of
      presenting with acute biliary pancreatitis. A policy of watchful waiting in such
      cases is unwarranted.

PMID- 9250229
TI  - Incidence and risk factors for serious hypoglycemia in older persons using
      insulin or sulfonylureas.
AB  - BACKGROUND: Our knowledge about the risk of hypoglycemia associated with diabetes
      treatment is derived from studies that often exclude frail, elderly persons.
      OBJECTIVE: To determine the incidence and risk factors for developing serious
      hypoglycemia among older persons using sulfonylureas or insulin. METHODS: We
      conducted a population-based, retrospective cohort study of 19932 Tennessee
      Medicaid enrollees, aged 65 years or older, who used insulin or sulfonylureas
      from 1985 through 1989. The main end point was serious hypoglycemia defined as a
      hospitalization, emergency department admission, or death associated with
      hypoglycemic symptoms and a concomitant blood glucose determination of less than
      2.8 mmol/L (< 50 mg/dL). RESULTS: We identified 586 persons with a first episode
      of serious hypoglycemia during 33,048 person-years of insulin or sulfonylurea
      use. The crude rates (per 100 person-years) of serious hypoglycemia were 1.23
      (95% confidence interval [CI], 1.08-1.38) in users of sulfonylureas and 2.76 (95%
      CI, 2.47-3.06) among insulin users. Recent hospital discharge was the strongest
      predictor of subsequent hypoglycemia in older persons with diabetes. The adjusted
      relative risk of serious hypoglycemia occurring in days 1 through 30 after
      hospital discharge was 4.5 (95% CI, 3.5-5.7) compared with the risk associated
      with a hypoglycemic event occurring 366 or more days after hospital discharge.
      Other independent risk factors included advanced age (relative risk, 1.8; 95% CI,
      1.4-2.3), black race (relative risk, 2.0; 95% CI, 1.7-2.4), and use of 5 or more
      concomitant medications (relative risk, 1.3; 95% CI, 1.1-1.5). CONCLUSIONS: In
      this population, the incidence of serious hypoglycemia is approximately 2 per 100
      person-years, suggesting that many older adults can be safely treated with
      hypoglycemic drugs. Frail, elderly persons--the oldest-old, those using multiple
      medications, and those who are frequently hospitalized--are at a higher risk for
      drug-associated hypoglycemia. Such individuals may benefit from intensive
      education about the symptoms of hypoglycemia and close monitoring for adverse
      events related to diabetes treatment.

PMID- 9250230
TI  - Antibiotic optimization. An evaluation of patient safety and economic outcomes.
AB  - BACKGROUND: Although numerous reports have described interventions designed to
      influence antibiotic utilization, to our knowledge none have been evaluated in a
      randomized study. METHODS: Adult inpatients receiving 1 or more of 10 designated
      parenteral antibiotics for 3 or more days during a 3-month period were randomized
      to an intervention (n = 141) and a control (n = 111) group using an unblocked,
      computer-generated random number table. Obstetric patients and those seen in
      infectious disease consultation were excluded. The intervention group received
      antibiotic-related suggestions from a team consisting of an infectious disease
      fellow and a clinical pharmacist. Both groups were evaluated for clinical and
      microbiological outcomes as well as antibiotic utilization via prospective chart
      reviews and analysis of the hospital's administrative database. RESULTS: Sixty
      two (49%) of the intervention group patients received a total of 74 suggestions.
      Sixty-three (84%) of these suggestions were implemented; the majority involved
      changes in antibiotic choice, dosing regimen, or route of administration. Per
      patient antibiotic charges were nearly $400 less in the intervention group vs
      controls (P = .05). Almost all the savings were related to lower intravenous
      antibiotic charges. Clinical and microbiological response, antibiotic-associated
      toxic effects, in-hospital mortality, and readmission rates were similar for both
      groups. Multiple linear regression analysis identified randomization to the
      intervention group and female sex as the sole predictors of lower antibiotic
      charges. There was a trend toward a shorter length of stay for the intervention
      group (20 vs 24.7 days, P = .11). CONCLUSIONS: This is the first randomized study
      to evaluate whether antibiotic choices can be influenced in a cost-effective
      fashion without sacrificing patient safety. We demonstrate that 50% of patients
      initially treated with expensive parenteral antibiotics can have their regimens
      refined after 3 days of therapy and that these modifications result in good
      clinical outcomes with a substantial reduction in antibiotic expense.

PMID- 9250231
TI  - Chronic headaches and sleep disorders.
AB  - BACKGROUND: Headaches and sleep problems are common complaints in the daily
      practice of the general practitioner. Since the relationship between headaches
      and sleep complaints is complex, clear models of interaction are needed for
      adequate diagnosis and treatment. METHODS: All subjects, successively seen in a
      headache clinic during a defined period, were subdivided based on the time of
      onset of cephalalgia. Subjects who reported onset of headache on a long-term
      basis, during the nocturnal or early morning (before final awakening) period,
      were systematically studied by a headache clinic and a sleep disorders center.
      This subgroup represented 17% of the total headache group. RESULTS: Although the
      results of the headache clinic study did not differentiate this subgroup from the
      other patients, the sleep disorders center's interviews and questionnaires
      demonstrated a significant impact of the sleep disorders on headache and daytime
      function. Nocturnal monitoring during sleep identified specific sleep disorders
      in 55% of the subjects with onset of headache during the nocturnal sleep period.
      Follow-up after treatment of the sleep disorder showed that all subjects with an
      identifiable sleep disorder reported either an improvement or absence of their
      headache. The subjects identified with periodic limb movement syndrome were
      mostly those who reported only an improvement in their sleep and still needed
      treatment for their headaches. The question of the interaction and association of
      sleep-related headache and periodic limb movement syndrome is unresolved.
      CONCLUSION: Headaches occurring during the night or early morning are often
      related to a sleep disturbance.

PMID- 9250233
TI  - The nicotine inhaler in smoking cessation.
AB  - BACKGROUND: Nicotine replacement therapy has been shown to improve success rates
      in smoking cessation treatment. However, the available products cause adverse
      effects, which prevent some smokers from using them. A new method of delivering
      nicotine via inhaler supplies nicotine orally through inhalation from a plastic
      tube. This mode of delivering nicotine resembles smoking, as it includes handling
      and active inhalation. OBJECTIVES: To assess the efficacy and safety of the
      nicotine inhaler as an aid in smoking cessation. METHODS: A 1-year, randomized,
      double-blind, placebo-controlled study was conducted in a smoking cessation
      clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day
      and who had previously made a serious attempt to stop smoking using nicotine
      chewing gum were recruited through advertisements. Randomization to treatment or
      control conditions were made at the first group session, with 123 participants
      receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were
      distributed at the second session and participants were allowed to use the
      inhalers for 6 months. MAIN OUTCOME MEASURE: Biochemically verified continuous
      abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months. RESULTS:
      Significantly more participants who had used the nicotine inhalers were
      continuously abstinent compared with those who had used the placebo inhalers. The
      respective success rates after 12 months were 28% and 18% (P = .046). At 6
      months, 20 participants (16%) in the nicotine group were still using the inhaler,
      compared with 4 (3%) in the control group (P < .001). CONCLUSION: The nicotine
      inhaler was an effective smoking cessation aid that produced a few mild and
      transient adverse effects.

PMID- 9250232
TI  - Incidence of community-acquired pneumonia requiring hospitalization. Results of a
      population-based active surveillance Study in Ohio. The Community-Based Pneumonia
      Incidence Study Group.
AB  - BACKGROUND: Pneumonia is the leading cause of death due to infectious diseases in
      the United States; however, the incidence of most infections causing community
      acquired pneumonia in adults is not well defined. METHODS: We evaluated all
      adults, residing in 2 counties in Ohio, who were hospitalized in 1991 because of
      community-acquired pneumonia. Information about risk factors, symptoms, and
      outcome was collected through interview and medical chart review. Serum samples
      were collected from consenting individuals during the acute and convalescent
      phases, and specific etiologic diagnoses were assigned based on results of
      bacteriologic and immunologic tests. RESULTS: The incidence of community-acquired
      pneumonia requiring hospitalization in the study counties in 1991 was 266.8 per
      100,000 population; the overall case-fatality rate was 8.8%. Pneumonia incidence
      was higher among blacks than whites (337.7/100,000 vs 253.9/ 100,000; P < .001),
      was higher among males than females (291.4 vs 244.8; P < .001), and increased
      with age (91.6/100,000 for persons aged < 45 years, 277.2/ 100,000 for persons
      aged 45-64 years, and 1012.3/ 100,000 for persons aged > or = 65 years; P <
      .001). Extrapolation from study incidence data showed the projected annual number
      of cases of community-acquired pneumonia requiring hospitalization in the United
      States to be 485,000. These data provide previously unavailable estimates of the
      annual number of cases that are due to Legionella species (8000-18,000),
      Mycoplasma pneumoniae (18,700-108,000), and Chlamydia pneumoniae (5890-49,700).
      CONCLUSIONS: These data provide information about the importance of community
      acquired pneumonia and the relative and overall impact of specific causes of
      pneumonia. The study provides a basis for choosing optimal empiric pneumonia
      therapy, and allows interventions for prevention of pneumonia to be targeted at
      groups at greatest risk for serious illness and death.

PMID- 9250234
TI  - Isoniazid preventive therapy in human immunodeficiency virus-infected persons.
      Long-term effect on development of tuberculosis and survival.
AB  - BACKGROUND: Although the short-term benefit of isoniazid prophylaxis in patients
      coinfected with human immunodeficiency virus (HIV) and tuberculosis has been
      shown, long-term benefits are unknown. METHODS: Historical cohort study in an
      acquired immunodeficiency syndrome unit at a tertiary referral hospital. A sample
      of 121 HIV-infected patients with positive results on a purified protein
      derivative test were followed up for development of active tuberculosis and
      survival. Patients who received isoniazid prophylaxis were compared with patients
      who did not receive prophylaxis. RESULTS: Of the 121 patients examined, 29 (24%)
      completed a 9- to 12-month course of isoniazid prophylaxis (median follow-up, 89
      months), and 92 (76%) did not receive the drug (median follow-up, 60 months).
      Active tuberculosis developed in 46 patients (38%). The incidence of tuberculosis
      was higher among patients with no prophylaxis (9.4 per 100 patient-years) than
      among patients with isoniazid prophylaxis (1.6 per 100 patient-years) (P = .006).
      Risk for development of tuberculosis was associated with the absence of isoniazid
      prophylaxis (relative risk [RR], 6.55; 95% confidence interval [CI], 2.02-21.19).
      Death during the period of study was more frequent in patients who did not
      receive isoniazid (50/92 or 54%) than in patients who received isoniazid (7/29 or
      24%) (P = .008). Median survival was more than 111 months in patients who
      received isoniazid compared with 75 months in patients who did not receive
      isoniazid (P < .001). In a proportional hazards analysis, the development of
      tuberculosis (RR, 1.88; 95% CI, 1.09-3.27), the absence of isoniazid prophylaxis
      (RR, 2.68; 95% CI, 1.16-6.17), and a CD4+ cell count lower than 0.20 x 10(9)/L
      (RR, 3.03; 95% CI, 1.39-6.61) were independently associated with death. Patients
      who received isoniazid had a longer survival after stratifying for the CD4+ cell
      count. CONCLUSIONS: Preventive therapy with isoniazid confers long-term
      protection against tuberculosis and significantly increases survival in patients
      dually infected with HIV and Mycobacterium tuberculosis.

PMID- 9250235
TI  - Bronchodilator delivery in acute airflow obstruction. A meta-analysis.
AB  - OBJECTIVE: To compare the effect of bronchodilator delivery by use of a metered
      dose inhaler (MDI) or wet nebulizer on objective measurements of acute airflow
      obstruction in adult patients. METHODS: Published and unpublished research was
      identified by MEDLINE searches for articles published from 1966 to 1994, review
      of scientific citations, review of article bibliographies, communication with
      experts in the area of asthma therapy and aerosol delivery, primary
      investigators, and a manufacturer of spacer devices. Eighteen studies were
      selected from 159 potentially relevant articles by independent review in
      triplicate. Selection criteria included randomized trials that compared
      bronchodilator delivery by use of an MDI and wet nebulizer in adults with acute
      exacerbations of asthma or chronic obstructive pulmonary disease who were treated
      in an emergency department or a hospital. Data for patient characteristics, study
      setting, bronchodilator doses, outcomes, and methodological quality were
      independently extracted. RESULTS: Twelve studies with a total of 507 patients had
      sufficient data to calculate an effect size (in SD units) for improvement in
      airflow obstruction after bronchodilator delivery. All but 2 studies used spacer
      devices with the MDI. The overall treatment effect size was -0.02 (95% confidence
      interval [CI], -0.20 to 0.16) that favored the MDI, but the magnitude of the
      effect size was not clinically or statistically significant. No significant
      effect was observed in the subgroup analyses that compared the diagnosis: asthma,
      -0.17 (CI, -0.41 to 0.07) compared with chronic obstructive pulmonary disease,
      0.23 (CI, -0.35 to 0.81); bronchodilator dose; or methodological quality. The
      results of a sensitivity analysis that included 5 of 6 excluded studies supported
      the findings from the primary analysis: 0.05 (CI, -0.11 to 0.20). CONCLUSIONS:
      Bronchodilator delivery by means of an MDI or wet nebulizer is equivalent in the
      acute treatment of adults with airflow obstruction. Spacer devices were used for
      bronchodilator delivery with an MDI in most studies and are recommended for the
      treatment of acute airflow obstruction. The choice of the delivery method will
      depend on the need for expedient treatment, availability of staff, consideration
      of costs, and findings from studies designed to evaluate treatment effects from
      larger than standard doses of bronchodilators delivered by use of an MDI.

PMID- 9250236
TI  - Population-based study of sleep-disordered breathing as a risk factor for
      hypertension.
AB  - BACKGROUND: Clinical observations have linked sleep-disordered breathing, a
      condition of repeated apneas and hypopneas during sleep, with hypertension but
      evidence for an independent association has been lacking. Understanding this
      relationship is important because the prevalence of sleep-disordered breathing is
      high in adults. OBJECTIVE: To test the hypothesis that sleep-disordered breathing
      is related to elevated blood pressure independent of confounding factors.
      METHODS: The sample included 1060 employed women and men aged 30 through 60 years
      who had completed an overnight protocol as part of the Wisconsin Sleep Cohort
      Study. In-laboratory polysomnography was used to determine sleep-disordered
      breathing status, quantified as the number of apneas and hypopneas per hour of
      sleep (apnea-hypopnea index). Blood pressure was measured on the night
      polysomnography was performed. RESULTS: Blood pressure increased linearly with
      increasing apnea-hypopnea index (P = .003 for systolic, P = .01 for diastolic,
      adjusted for confounding factors). The magnitude of the linear association
      increased with decreasing obesity. At a body mass index (weight in kilograms
      divided by the square of the height in meters) of 30 kg/m2, an apnea-hypopnea
      index of 15 (vs 0) was associated with blood pressure increases of 3.6 mm Hg for
      systolic (95% confidence interval, 1.3-6.0) and 1.8 mm Hg for diastolic (95%
      confidence interval, 0.3-3.3). The odds ratio for hypertension associated with an
      apnea-hypopnea index of 15 (vs 0) was 1.8 (95% confidence interval, 1.3-2.4).
      CONCLUSIONS: There is a dose-response relationship between sleep-disordered
      breathing and blood pressure, independent of known confounding factors. If
      causal, the high prevalence of sleep-disordered breathing could account for
      hypertension in a substantial number of adults in the United States.

PMID- 9250238
TI  - MALTomas of the thyroid.

PMID- 9250237
TI  - Clinical and ethical issues in the treatment of a Jehovah's Witness with acute
      myeloblastic leukemia.
AB  - We report the first documented case of the use of peripheral blood stem cell
      autografting in the treatment of a Jehovah's Witness with acute myeloblastic
      leukemia. This case illustrates the complex ethical and clinical issues that
      arise in the treatment of such patients.

PMID- 9250239
TI  - Predictive properties of serum prostate-specific antigen testing in a community
      setting.

PMID- 9250240
TI  - Practical legal comments on informed consent.

PMID- 9250241
TI  - Alcohol and cardiovascular mortality in US physicians: is there a modifier effect
      by low-density lipoprotein?

PMID- 9250242
TI  - Survival among severely cognitively impaired tube-fed nursing home residents.

PMID- 9250243
TI  - Indications for inferior vena cava filters.

PMID- 9250244
TI  - Lack of evidence for an association between Helicobacter pylori infection and the
      anorexia of aging.

PMID- 9250245
TI  - The German health system: lessons for reform in the United States.

PMID- 9250246
TI  - Dose of exercise and health benefit.

PMID- 9250247
TI  - Sliding scale insulin use.

PMID- 9250248
TI  - Comments on the safety of antioxidant vitamin supplementation.

PMID- 9250249
TI  - Pregnancy and asthma.

PMID- 9250250
TI  - Pregnancy and asthma.

PMID- 9250251
TI  - Assessment of asthma using automated and full-text medical records.
AB  - Automated medical records systems are used to study clinical outcomes and quality
      of care, but this requires accurate disease identification and assessment of
      severity. We sought to determine the reliability of identifying asthmatics
      through automated medical and pharmacy records, and the adequacy of such data for
      severity assessment. All adult health maintenance organization (HMO) members who
      received at least one asthma drug and an asthma diagnosis between April 1988 and
      September 1991 were identified. Records of a random sample were reviewed to
      validate the diagnosis and extract clinical information. Asthma drugs were
      dispensed to 15,491 individuals; 7583 (49%) also received an asthma diagnosis.
      Asthma drug use was three times greater for persons with diagnosed asthma
      compared to those with no diagnosis. Record review revealed that a coded asthma
      diagnosis had a positive predictive value of 86%. Nearly 4000 ambulatory
      encounters were reviewed, 10% of which were for asthma; the median number of
      encounters was two. Asthma symptoms were mentioned in 9% of all encounters;
      wheezing was most common. Peak flow and spirometry were measured in 4% and 1% of
      encounters, respectively. Records from recipients of asthma drugs who lacked an
      asthma diagnosis showed that 79% did not have asthma. Automated medical and
      pharmacy records from an HMO were relatively accurate when used to identify
      individuals with asthma. Similarly, most asthma drug recipients who lacked a
      coded diagnosis of asthma did not have asthma. However, conventional full-text
      records usually do not contain sufficient information to assess asthma severity,
      limiting the utility of such records for research and quality improvement.

PMID- 9250252
TI  - Furosemide given by inhalation ameliorates acute exacerbation of asthma.
AB  - Previous studies have suggested that inhaled furosemide may have a protective
      effect against a wide variety of bronchoconstrictor agents, but a therapeutic
      effect has not been established in acute exacerbation of asthma. The purpose of
      this study was to investigate whether inhaled furosemide would exhibit any
      therapeutic benefit in acute asthma. We conducted a double-blind, placebo
      controlled, randomized study in 40 patients with acute mild or moderate
      exacerbation of asthma. All patients received intravenous (i.v.) aminophylline
      250 mg for 90 min and i.v. hydrocortisone 100 mg at entry. After randomization, 3
      patients were excluded from the final analysis. At 30 min after starting i.v.
      aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients
      received normal saline as placebo-control. Both inhalations were given by a jet
      nebulizer. The baseline forced expiratory volume at 1 sec (FEV1), peak expiratory
      flow rate (PEFR), and serum concentration of theophylline did not differ between
      the two groups. An increase in FEV1 in the furosemide group by 28.2 +/- 5.9%
      (mean +/- SE) was noted at 60 min, and this was significantly higher than in the
      control group. PEFR at 60 min was also significantly higher in the furosemide
      group than in control group. We conclude that inhaled furosemide has a
      bronchodilator effect on mild to moderate exacerbation of asthma when it is used
      with i.v. theophylline. Inhaled furosemide may benefit certain acute asthma
      patients, especially those suffering complications from the adverse effects of
      beta 2-agonists.

PMID- 9250253
TI  - Toward a simplified measure of asthma severity for applied research.
AB  - There is no universally accepted and validated measure of asthma severity. For
      community research, clinical tests are too costly, and epidemiological
      assessments provide inadequate data on severity. Symptom measures may offer a
      practical alternative. This study assessed psychometric properties of symptom
      ratings of 91 asthmatic children. Reliability and validity of scales created from
      these items were examined. A sum scale of symptom ratings was internally
      consistent, reliable across time, and associated with concurrent health indices.
      This scale may be a practical measure of severity for use in community-based
      research.

PMID- 9250254
TI  - Laboratory and clinical evaluation of a portable computerized peak flow meter.
AB  - A mini-Wright based peak flow meter (VMX Mini-Log), which stores the readings
      together with the time and date of each measurement, has recently been marketed
      but has not yet been evaluated. The accuracy, reproducibility, and interdevice
      variability of this instrument were investigated using a pneumotachograph
      connected in series as a standard. Flows from 100 to 700 L/min were generated by
      an explosive decompression chamber. The performance of this instrument was also
      tested in 20 normal subjects and in 20 patients with airflow obstruction. The
      accuracy of the instrument was expressed as the percentage of error, and
      reproducibility and interdevice variability were assessed using the coefficient
      of variation. In the laboratory evaluation, all devices recorded flow rates that
      were within +/-10% of the pneumotachograph readings at flows between 200 and 600
      L/min. At the extreme flow rates of 100 and 700 L/min, the mean error was higher
      than 10%. The reproducibility of the VMX was within +/-5% at all the flows
      tested. The interdevice variability was less than 5% at flow rates between 200
      and 700 L/min. When tested on normal subjects with PEF between 400 and 700 L/min,
      the VMX performed well. In patients with airflow obstruction, four devices had
      greater than 10% error. The largest error was observed in those patients with PEF
      below 200 L/min. The VMX Mini-Log peak flow meter is accurate and precise in the
      flow range between 200 and 600 L/min. Its performance, however, may be affected
      in subjects with airflow obstruction and PEF below 200 L/min.

PMID- 9250255
TI  - Comparison of sputum and serum eosinophil cationic protein (ECP) levels in
      nonatopic asthma and chronic obstructive pulmonary disease.
AB  - The aim of the present study was to investigate whether sputum eosinophil
      cationic protein (ECP) concentrations could be a useful marker in the
      differential diagnosis between intrinsic asthma and chronic obstructive pulmonary
      disease (COPD). For this purpose total blood eosinophil counts were obtained and
      concentrations of serum and sputum ECP from 10 nonatopic asthmatics with a mild
      attack and 9 COPD patients with acute exacerbation were measured by
      radioimmunoassay. Mean serum ECP concentration was 54.3 +/- 23.0 micrograms/L in
      the asthmatic group and 83.3 +/- 79.2 micrograms/L in the COPD group (p: n.s.).
      In the group of asthmatics mean sputum ECP level was 984.5 +/- 1245.5
      micrograms/L/g sputum and in the COPD group it was 417.5 +/- 363.5 micrograms/L/g
      sputum. There was no significant difference in sputum ECP levels between patients
      with asthma and COPD. We conclude that neither sputum nor serum ECP levels are
      useful markers in differential diagnosis of asthma attack and acute exacerbation
      of COPD.

PMID- 9250256
TI  - Results of the first U.S. double-blind, placebo-controlled, multicenter clinical
      study in asthma with pranlukast, a novel leukotriene receptor antagonist.
AB  - Pranlukast (SB 205312; ONO-1078), a potent, orally active selective cysteinyl
      leukotriene receptor antagonist (LTRA), was developed in Japan for the treatment
      of asthma. This article reports results of the initial U.S. clinical evaluation
      of pranlukast. The primary objective of this multicenter study was to evaluate
      the safety and tolerability of pranlukast administered at doses of 337.5 mg
      b.i.d. and 450 mg b.i.d. in 65 patients with mild to moderate asthma. Pranlukast,
      a novel LTRA, is safe and well tolerated at doses of 337.5 mg b.i.d. and 450 mg
      b.i.d. Pranlukast has demonstrated clinical activity in patients with asthma.

PMID- 9250257
TI  - The association of nocturnal asthma with asthma severity.
AB  - The objective of this study is to assess nocturnal asthma as a marker for poor
      control of asthma. Cross-sectional study of asthmatic patients was conducted in
      six general practices in East Anglia, England. Subjects were 240 asthma patients,
      between the ages of 20 and 54 years, from the above general practices. A
      continuous asthma severity score (range 6-26), consisting of the summation of
      ordinal responses to questions regarding asthma symptoms during the last 6
      months, was used for analysis. The crude association between nocturnal asthma and
      severity score was statistically highly significant. Regression analysis suggests
      that, after controlling for possible confounding variables, there remains a
      strong association between nocturnal asthma (NA) and severity, which is modified
      by self-report of current consultation for "nervous/emotional trouble" (current
      NT). In the absence of current NT, NA raises the severity score by 5.3 (95% CI
      4.5, 6.2), whereas in the presence of current NT, NA raises the severity score by
      8.2 (95% CI 4.8, 11.6). NA appears promising as a marker for poorly controlled
      asthma. Confirmation of the association found in this study by objective measures
      of severity would strengthen the utility of NA as a marker.

PMID- 9250259
TI  - Caring for the severely asthmatic child and family. I. The rationale for family
      systems integrated medical/psychological treatment.
AB  - Comprehensive care for the severely asthmatic child includes psychological as
      well as medical treatment. Family therapy is a recognized modality of therapy.
      Investigations have examined the role of emotion and asthma as well as
      psychosomatic asthma. Pharmacological treatment of beta 2-agonist and cromolyn
      prior to disciplining the child prevents psychosomatic asthma secondary to crying
      or shouting. Adherence to multiple asthma therapeutic modalities is imperative,
      and a psychological and medical team can address these important clinical issues
      in a high-risk population.

PMID- 9250258
TI  - Effect of pretreatment with heparin on pulmonary and cutaneous response.
AB  - Although anticoagulant properties of glycosaminoglycan heparin are primary in
      medicine, a variety of other biological functions related to heparin have been
      suggested. Since heparin is a selective inhibitor of inositol triphosphate (IP3)
      receptors that are involved in release of calcium in mast cells and many other
      cells, it is possible that heparin may act as a natural anti-inflammatory
      molecule and modify these reactions. Therefore, the purpose of the present study
      was to determine the role of heparin in allergic inflammatory responses: the
      pulmonary reaction and the cutaneous response, in a double-blind, placebo
      controlled, crossover randomized trial. To evaluate the effect of heparin on
      methacholine-induced bronchoconstriction, nebulized heparin (20,000 units) was
      administered to 12 asthmatics and nonspecific challenge was performed immediately
      thereafter. Measurements of Raw and SGaw were obtained before and 1 hr after
      nebulization of heparin. In 12 other allergic subjects, heparin (25 U/kg) was
      given intravenously 10 min before skin prick test. We demonstrated that
      pretreatment with heparin reduced skin test reactivity from 24.06 +/- 1.2 mm to
      18.26 +/- 2.27 mm and increased the methacholine PC20 value from 1.69 +/- 0.48
      mg/ml to 8.14 +/- 3.11 mg/ml (p < 0.05), but did not prevent an increase in Raw
      and/or a decrease in SGaw. Heparin modified the methacholine-induced
      bronchoconstrictor response, but this did not reflect a protective effect in
      airway resistance and specific conductance. These data suggest that anti
      inflammatory effects of heparin are time-dependent and/or that heparin may have a
      transient inhibitory role in allergic reactions.

PMID- 9250260
TI  - The next stage: molecular epidemiology.
AB  - The traditional approach in epidemiology of relating exposure to an environmental
      agent such as a drug or infective agent has been to measure an overall risk
      (i.e., average and then "adjust risk for demographic variables and other
      confounders"). An attempt is sometimes made to define a "susceptible" subgroup.
      The analyses are usually based on good statistical methodology rather than an
      understanding of the interaction of body of host and agent. A twofold risk for
      1000 exposed versus nonexposed people could be an average twofold risk for all
      1000 exposed or a 20-fold risk for 100 exposed individuals (i.e., a drug-host
      interaction). Clearly, finding the 100 individuals with a 20-fold risk has much
      greater clinical importance than a twofold risk for 1000 people. The world of
      epidemiology may be changing-we may soon be able to define risk based on genetic
      susceptibility, at least sometimes.

PMID- 9250261
TI  - Should the definition for the negative likelihood ratio be changed?

PMID- 9250262
TI  - Should the definition for the negative likelihood ratio be changed?

PMID- 9250263
TI  - Joint analysis of three U.S. community intervention trials for reduction of
      cardiovascular disease risk.
AB  - During the 1980s three comprehensive community-based heart disease prevention
      trials were conducted in the United States. The Stanford Five-City Project,
      Minnesota Heart Health Program, and Pawtucket Heart Health Program involved 12
      cities; six received a 5-8 year multifactorial risk reduction program. This
      analysis pools data from the three studies to delineate the common intervention
      effects with greater sample size and power than could be attained by the single
      studies. Time trends were estimated for cigarette smoking, blood pressure, total
      cholesterol, body mass index, and coronary heart disease mortality risk in women
      and men aged 25-64 years. The joint estimates of intervention effect were in the
      expected direction in nine of 12 gender-specific comparisons; however, these were
      not statistically significant. The results illustrate the analytic challenges of
      evaluating community-based prevention trials and point to the smaller than
      expected net differences, rather than small sample size, as the reason for few
      statistically significant effects in the three U.S. prevention trials.

PMID- 9250264
TI  - Diagnostic utility of the history and physical examination for peripheral
      vascular disease among patients with diabetes mellitus.
AB  - BACKGROUND: We assessed the value of the medical history and physical examination
      in the diagnosis of peripheral vascular disease in diabetic subjects. METHODS: We
      performed a cross-sectional study in 631 diabetic veteran enrollees of a general
      internal medicine clinic that compared data obtained from a history and clinical
      evaluation with the presence of severe peripheral vascular disease defined as an
      ankle-arm index (AAI) < or = 0.5 derived from Doppler blood pressure measurement.
      RESULTS: We identified 90 limbs with an AAI < or = 0.5. Results presented below
      apply to the right leg, but do not differ from the left. Diminished or absent
      foot peripheral pulses (sensitivity 65%, specificity 78%), venous filling time >
      20 sec (sensitivity 22%, specificity 93.9%), age > 65 years (sensitivity 83%,
      specificity 54%), claudication symptoms in < 1 block (sensitivity 50%,
      specificity 87%), and patient reported history of physician diagnosed peripheral
      vascular disease (PVD) (sensitivity 80%, specificity 70%) had the largest
      positive (or smallest negative) likelihood ratios. Capillary refill time > 5 sec
      or foot characteristics (absent hair, blue/purple color, skin coolness, or
      atrophy) conveyed little diagnostic information. Individual factors did not
      change disease probability to a clinically important degree. A stepwise logistic
      regression model identified four factors significantly (p < 0.05) associated with
      low AAI: absent or diminished peripheral pulses, patient reported history of PVD,
      age, and venous filling time. Substitution of < 1 block claudication for PVD
      history in this model resulted in a small reduction in model accuracy.
      CONCLUSIONS: Many purportedly useful historical and exam findings need not be
      elicited in diabetic patients suspected of having severe peripheral vascular
      disease, since most information related to probability of this disorder may be
      obtained from patient age, self-reported history of physician diagnosed PVD (or <
      1 block claudication), peripheral pulse palpation, and venous filling time.

PMID- 9250265
TI  - Correlates of back problems and back-related disability in the United States.
AB  - The purpose of this study is to identify correlates of back problems and back
      disability in the adult population of the United States. Cross-sectional analyses
      were performed using data from the 1989 National Health Interview Survey (NHIS).
      Weighted polytomous logistic regression modeling was performed to estimate odds
      ratios adjusted for the effects of covariates. The prevalence of a disabling back
      condition, vs. no back condition, was relatively higher among subjects aged 25-64
      years, male, non-high-school graduates, unemployed, living in the West, with
      disabling non-back morbidities, and with body mass index and weight above the
      50th percentile. Among workers, those in technical, sales, clerical, private
      household, service, precision production and repair, or transportation
      occupations were relatively more likely to report disabling back conditions,
      compared to workers in professional occupations. Among adults with back problems,
      age greater than 34 years, weight above the 50th percentile, and history of back
      trauma were associated with chronic back disability. Although the magnitudes of
      the associations are not large, they may have enormous public health implications
      because of the high prevalence of back problems and related disability.

PMID- 9250266
TI  - The results of direct and indirect treatment comparisons in meta-analysis of
      randomized controlled trials.
AB  - When little or no data directly comparing two treatments are available,
      investigators often rely on indirect comparisons from studies testing the
      treatments against a control or placebo. One approach to indirect comparison is
      to pool findings from the active treatment arms of the original controlled
      trials. This approach offers no advantage over a comparison of observational
      study data and is prone to bias. We present an alternative model that evaluates
      the differences between treatment and placebo in two sets of clinical trials, and
      preserves the randomization of the originally assigned patient groups. We apply
      the method to data on sulphamethoxazole-trimethoprim or dapsone/pyrimethamine as
      prophylaxis against Pneumocystis carinii in HIV infected patients. The indirect
      comparison showed substantial increased benefit from the former (odds ratio 0.37,
      95% CI 0.21 to 0.65), while direct comparisons from randomized trials suggests a
      much smaller difference (risk ratio 0.64, 95% CI 0.45 to 0.90; p-value for
      difference of effect = 0.11). Direct comparisons of treatments should be sought.
      When direct comparisons are unavailable, indirect comparison meta-analysis should
      evaluate the magnitude of treatment effects across studies, recognizing the
      limited strength of inference.

PMID- 9250268
TI  - Carcinoid tumors of the lung and family history of cancer.
AB  - Family history of cancer has been described among patients with lung neoplasms.
      Carcinoid tumors, originally thought to be slow growing and nonmetastatic, have
      not historically been included in these studies. In some instances these tumors
      have demonstrated aggressive metastatic potential. A medical record review of 86
      patients with histopathologically confirmed carcinoid tumors of the lung, treated
      at the University of Texas M.D. Anderson Cancer Center between 1959 and 1994, was
      conducted to describe family history of cancer. Family history of cancer was
      recorded in 74 (86%) of the medical records and 32 (43%) reported first-degree
      relatives with cancer. Five-year survival for patients with affected relatives
      was 45% and 73% for patients without affected relatives (p = .23). Among 67
      patients without metastatic disease at diagnosis, the risk of distant metastasis
      by 5 years was 40% among patients with a positive family history of cancer
      compared to 6% of the patients without affected relatives (p = .03), (rate ratio
      5.01). These results suggest that genetic susceptibility may affect the
      metastatic potential of some carcinoid tumors.

PMID- 9250267
TI  - Association of serum albumin and mortality risk.
AB  - Reduced levels of serum albumin concentration, a routine blood test, within the
      "normal" range have been reported to be associated with mortality risk. The
      literature is reviewed, with a focus on cohort studies meeting specified
      criteria, and findings are summarized. In studies of many populations, comprising
      healthy subjects and patients with acute or chronic illness, serum albumin
      concentration is inversely related to mortality risk in a graded manner over its
      entire range; the estimated increase in the odds of death ranges from 24% to 56%
      for each 2.5 g/l decrement in serum albumin concentration. The association
      predicts overall and cause-specific mortality including cardiovascular mortality.
      It is likely that albumin concentration is a highly sensitive indicator of
      preclinical disease and disease severity. A direct protective effect of the
      albumin molecule is suggested by the persistence of the association after
      adjustment for other known risk factors and preexisting illness, and after
      exclusion of early mortality. Although biologically plausible, there is no direct
      evidence for this hypothesis. Serum albumin concentration is an independent
      predictor of mortality risk and could be useful in the quantification of risk in
      a broad range of clinical and research settings.

PMID- 9250269
TI  - Comparison of survey and physician claims data for detecting hypertension.
AB  - Using linked data from the Manitoba (Canada) Heart Health Survey (MHHS) and
      physician service claims files we assessed the degree to which self-reported
      hypertension and clinically measured hypetension agreed with physician claims
      hypertension, and examined the likely sources of disagreement. The overall
      agreement between survey and claims data for hypertension detection was moderate
      to high: 82% (kappa = 0.56) for self-reported and physician claims hypertension,
      and 85% (kappa = 0.60) for clinically measured and physician claims hypertension.
      In the comparison between self-report and physician claims, those who were
      classified as obese, diabetic, or a homemaker were significantly more likely to
      have a hypertension measure not confirmed by the other. Disagreement between
      clinically measured and physician claims was also more common among the obese and
      homemakers, as well as those on medication for heart diseases, elevated
      cholesterol levels (LDL), and 35 years of age and older. The high overall level
      of agreement among these three measures suggest that each may be used with
      confidence as an indication of hypertension; however, the agreement appears lower
      among individuals presenting a more complicated clinical profile.

PMID- 9250270
TI  - Cohort study of ethnic group and cardiovascular and total mortality over 15
      years.
AB  - Altogether, 3365 men and 3266 women who attended two cardiovascular screenings in
      1974-1975 and 1977-1978, have been followed with respect to death for an average
      of 15 years. The mortality from coronary heart disease was lower in men who
      reported being of Lappish origin than in men who reported Norse origin at both
      screenings (Rate ratio: 0.38 [0.20-0.71]), when other major risk factors were
      taken into account. Among men without history of cardiovascular disease or
      symptoms of angina pectoris the rate ratio became 0.24 (0.09-0.63). With
      cardiovascular death as the endpoint, the corresponding rate ratios were 0.42
      (0.25-0.73) and 0.31 (0.15-0.67). In women, a non-significant lower mortality was
      seen in the Lappish group than in the Norse group. This study is suggestive of
      some protection from coronary heart disease in middle-aged men of Lappish origin.

PMID- 9250271
TI  - Comorbidity measurement in elderly female breast cancer patients with
      administrative and medical records data.
AB  - The inter-rater reliability, cross-source (Medicare claims versus medical record)
      agreement, and ability to predict all-cause mortality of three aggregate
      comorbidity indices were evaluated in a group of 404 elderly, incident breast
      cancer cases identified from the Virginia Cancer Registry and linked to Medicare
      administrative data files. Comorbidity was based on both medical records and
      Medicare claims data using indices from Charlson et al (1987), Satariano and
      Ragland (1994), and Kaplan and Feinstein (1974). Inter-rater agreement was good
      for all indices (kappas > or = 0.80). Agreement between comorbidity indices
      measured by claims and medical records was considerably poorer (kappas between
      0.30 and 0.40). However, claims-based and medical records-based comorbidity
      indices were similarly associated with mortality. For the Charlson index, the
      index best predicting survival, the adjusted relative risk for an increase from a
      lower to higher comorbidity category was 1.48 (95% confidence interval 1.23,
      1.78) based on medical records compared to 1.53 (95% confidence interval 1.23,
      1.93) based on Medicare claims. The claims-based Charlson index score still
      appeared to be associated with survival (relative risk = 1.30; 95% confidence
      interval = 1.00, 1.70) after controlling for the medical records-based score.
      This suggests that both comorbidity data sources add valuable prognostic
      information and, conversely, that the use of either source alone will result in
      some misclassification of comorbidity.

PMID- 9250273
TI  - Clinical prediction rules.

PMID- 9250272
TI  - Rates of hypoglycemia in users of sulfonylureas.
AB  - OBJECTIVE: To identify the demographic and clinical characteristics of
      sulfonylurea users. To assess the risk of hypoglycemia in patients treated with
      sulfonylureas in clinical practice, and to characterize the risk in relation to
      the different drugs used. RESEARCH DESIGN AND METHODS: A cohort of 33,243
      sulfonylurea users chosen from 719 clinical practices in the United Kingdom were
      identified through the VAMP-Research database. Information on demographic
      characteristics, medical diagnoses and use of medical services was obtained
      through the computerized records. For a stratified sample of 500 patients,
      general practioners completed a structured questionnaire on the duration,
      treatment, and complications of diabetes mellitus, obesity, alcohol use, and
      smoking history. Patients with a diagnosis of hypoglycemia, as recorded in the
      database within a time-window of a sulfonylurea prescription, were identified.
      Incidence rates per person-year of sulfonylurea therapy were estimated. RESULTS:
      Other than a longer duration of diabetes in users of chlorpropamide, no
      differences were observed among users of different sulfonylurea agents with
      respect to diabetic complications, adequacy of diabetic control, obesity,
      smoking, and excessive alcohol consumption. A diagnosis of hypoglycemia during
      sulfonylurea therapy was recorded in 605 people over 34,052 person-years of
      sulfonylurea therapy, which converted into an annual risk of 1.8%. The risk in
      glibenclamide users was higher than in users of other types of sulfonylureas
      uses. Duration of therapy, concomitant use of insulin, sulfonylurea-potentiating
      or antagonizing and concomitant use of beta-blockers were predictive of the risk
      of developing hypoglycemia. DISCUSSION: Drug use patterns showed comparability
      among users of different sulfonylurea agents. Our findings suggest that the rate
      of diagnosis of hypoglycemia made by physicians is higher for glibenclamide than
      for other sulfonylureas. An epidemiological study with objectively diagnosed
      hypoglycemia should be undertaken to confirm these results.

PMID- 9250274
TI  - Criteria for classifying endocarditis.

PMID- 9250275
TI  - The changing face of macrovascular disease in non-insulin-dependent diabetes
      mellitus: an epidemic in progress.

PMID- 9250276
TI  - The epidemiology of cardiovascular disease in type 2 diabetes mellitus: how sweet
      it is ... or is it?

PMID- 9250277
TI  - Vascular dysfunction in diabetes mellitus.

PMID- 9250278
TI  - Non-invasive assessment of cardiovascular disease in diabetes mellitus.

PMID- 9250279
TI  - Lipids and lipoproteins as coronary risk factors in non-insulin-dependent
      diabetes mellitus.

PMID- 9250280
TI  - What cardiologists need to know about diabetes.

PMID- 9250281
TI  - The impact of cardiovascular disease on people with diabetes: the potential for
      prevention.

PMID- 9250282
TI  - Immature cells and Helicobacter pylori infection in early gastric cancer. An
      immunohistochemical study.
AB  - BACKGROUND: Helicobacter pylori (HP) infection has been frequently pointed out as
      one of factors involved in gastric carcinogenesis: in fact, the risk of
      developing gastric cancer is 4-6 times higher in infected than in non infected
      subjects. MATERIALS AND METHODS: In the present study the mucopeptic cells
      (immature cells) expansion was evaluated in 15 patients with intestinal type
      early gastric cancer (EGC): the cases were subdivided in relation with HP
      infection in the surrounding areas. RESULTS: Foveolar mucopeptic cells expansion
      was present in 63.6% of HP positive EGC patients. This phenomenon was not
      observed in HP negative EGC. In case of HP positive EGC there is foveolar
      expansion of the mucopeptic department with substitution of mature cells with
      immature ones. CONCLUSIONS: Therefore, HP, by means of alteration of cellular
      turn-over, could act as a promoter in the progression towards neoplasia,
      modulating the risk acting over individual genetical susceptibility. That even
      independently from atrophic gastritis.

PMID- 9250283
TI  - Interferon plus ursodeoxycholic acid versus interferon in the treatment of
      chronic C viral hepatitis.
AB  - BACKGROUND: The aim of as study was to ascertain whether the association of
      interferon alpha-2a and ursodeoxycholic acid (IFN+UDCA) was more efficacious in
      ameliorating liver parameters than interferon (IFN) alone in patients with
      chronic hepatitis C. METHODS: Forty-one chronic hepatitis C patients, who had at
      least twice the normal value of one transaminase, were randomly assigned to
      treatment with IFN + UDCA (n = 21) or IFN alone (n = 20). IFN was administered
      subcutaneously at a dose of 3 MU thrice weekly, UDCA orally at 10 mg/kg bw/day.
      IFN therapy was terminated 6 months later and the responders (normalized
      transaminases) of both groups were treated with UDCA alone for a further 12
      months. RESULTS: In the IFN + UDCA group there were 2 drop-outs from therapy and
      11 responders, while in the IFN group they were, respectively, 3 and 10.
      Transaminases normalized after the first month of treatment in 7/11 responders
      with IFN + UDCA compared with 3/10 in the IFN responders group. The trend to
      normalization was more rapid with IFN + UDCA than with IFN alone (chi 2t = 3.95;
      p < 0.05). Disease relapse (defined as at least one transaminase > x 1.5 the
      normal value) was 3/11 in the IFN + UDCA group and 4/10 in the IFN group. 2/11
      responders in the IFN + UDCA and 1/10 in the IFN group were HCV RNA negative by
      PCR. The total Knodell histological score decreased more in the IFN+UDCA than in
      the IFN group (-2.67 +/- 3.44. vs -1.67 +/- 2.16, mean +/- SD). CONCLUSIONS: The
      administration of UDCA determine an earlier normalization-time of transaminases
      in the patients responders to IFN therapy and could be useful to reduce the
      relapse into disease after the IFN therapy.

PMID- 9250284
TI  - Unusual case of pulmonary rickettsiosis in non-Hodgkin's lymphoma.
AB  - A case report of boutonneuse fever with pulmonary complications in a patient with
      non-Hodgkin's lymphoma (NHL) is described. The patient was hospitalized for
      persistent hypertermia and marked dyspnea, with radiographic findings of
      bilateral involvement of the lungs. The confirmation of the diagnosis was
      obtained by means of serum analyses (Weil-Felix serodiagnosis and IFA); the
      patient responded to doxycycline with progressive improvement of her general
      health condition. In this case the occurrence of a NHL could justify the lower
      reactivity and the facilitated diffusion of rickettsiosis in the patient.

PMID- 9250285
TI  - Ameloblastoma. Cytologic findings and literature review.
AB  - OBJECTIVE: To define and elaborate the cytomorphologic features of primary and
      metastatic ameloblastoma (ABL) on fine needle aspiration (FNA) and to discuss the
      differential diagnosis with closely related entities and review the cytologic
      literature on the subject. STUDY DESIGN: A retrospective study consisting of five
      cases of ameloblastomas, primary in the mandible (n = 3) and metastases (n = 2),
      diagnosed by FNA cytology with appropriate cytohistologic correlation, was done.
      Smears were stained with the Diff-Quik and Papanicolaou methods. Hematoxylin and
      eosin-stained sections of paraffin block as well as sections from the surgically
      resected specimens were also reviewed. RESULTS: The smears were hypercellular and
      occasionally showed tissue fragments of basaloid cells with peripheral
      palisading. A distinct, two-cell population was seen, consisting of small,
      hyperchromatic, basaloid-type cells and scattered larger cells with more open
      chromatin. Occasional fragments of mesenchymal cells with more elongated nuclei
      and ample, clear cytoplasm were also noted. Malignant cases that metastasized
      showed prominent cytologic pleomorphism, cellular crowding with molding and a
      high mitotic/karyorrhectic index. CONCLUSION: In the right clinical setting and
      with proper radiologic evidence, the cytologic features of primary and metastatic
      ameloblastoma are unique. Diagnostic problems may arise when these lesions are
      pleomorphic and frankly malignant, especially at metastatic sites, such as the
      lung. FNA, therefore, is a valuable diagnostic tool in the initial diagnosis and
      follow-up of patients with a history of ameloblastoma.

PMID- 9250286
TI  - Adenocarcinoma in females detected in serous effusions. Cytomorphologic aspects
      and immunocytochemical reactivity to cytokeratins 7 and 20.
AB  - OBJECTIVE: To investigate the usefulness of assessing the immunoreactivity of
      cytokeratins 7 (CK7) and 20 (CK20) as well as several cytomorphologic parameters
      in effusions with metastatic adenocarcinomas in the search for the primary site
      of the tumor. STUDY DESIGN: From the files of the Pathology Department, A. C.
      Camargo Hospital, we studied cytologic smears from 73 metastatic adenocarcinomas
      originally from the breast, 63 from the ovary, 40 from the lung and 32 from the
      stomach, looking for morphologic parameters that could have discriminant
      potential in suggesting the primary site in a routine situation, including
      intranuclear inclusions, prominent nucleoli, mitosis, signet-ring cells, psammoma
      bodies, nuclear crease, binucleation and multinucleation, papillary features,
      acinar profile (including ball cells) and single cells. Immunoreactions were
      performed with monoclonal antibodies to CK7 (OV-TL 12/30) and CK20 (Ks 20.8) and
      included morphologic analysis. Both analyses were studied in a blind fashion
      regarding the primary site of the tumors. RESULTS: Positivity ratios for breast,
      ovary, stomach and lung cases were 67.6%, 63.5%, 29.7% and 45.5%, respectively,
      for CK7 and 17.2%, 15.8%, 13.5% and 32.2%, respectively, for CK20. Discriminant
      analysis of morphologic and immunocytochemical parameters had an error rate of
      42.9% in recognizing the primary site and a Wilk's lambda of .7290. CONCLUSION:
      The more efficient parameter with discriminant function was the papillary
      appearance showed by CK7, which should be used in further studies with a similar
      scope. The set of parameters used in this study were insufficient to discriminate
      the primary site of female adenocarcinomas in effusions with significant
      accuracy.

PMID- 9250287
TI  - Cytologic diagnosis of pancreatic cystic lesions. A prospective study of 28
      percutaneous aspirates.
AB  - PURPOSE: To prospectively evaluate fine needle aspiration biopsy (FNAB) of
      pancreatic cystic lesions. STUDY DESIGN: We performed a blind, prospective study
      on percutaneous aspirates from 28 radiographically identified cysts, including 6
      inflammatory cysts (5 pseudocysts and 1 abscess), 4 serous cystadenomas, 1 cystic
      islet cell tumor, 5 mucinous cystic neoplasms, 6 mucinous cystadenocarcinomas and
      6 nonpancreatic cysts. RESULTS: Four of six (67%) cystadenocarcinomas were
      identified as malignant, and the other two, which lacked sufficient morphologic
      criteria for malignancy, as consistent with mucinous cystic neoplasm. Two of five
      mucinous cystic neoplasms were correctly classified. One, which contained
      atypical cells, did not appear to be mucinous on the ThinPrep, and one, which
      lacked an epithelial component, was suggested because of the presence of mucin in
      the background. The fifth one contained inflammatory cells only. One of four
      serous cystadenomas produced a diagnostic specimen. FNAB of the cystic islet cell
      tumor was nondiagnostic. Five of six inflammatory cysts (83%) were correctly
      diagnosed, whereas one case produced an acellular, nondiagnostic specimen. Six of
      28 (23%) cases were nonpancreatic cysts, aspirated under the presumption that
      they were pancreatic cysts based on radiologic studies: only one case, a
      papillary cystadenocarcinoma of the stomach, was correctly diagnosed; the other
      five cases were nondiagnostic, and in two of these the assumption that the cysts
      were pancreatic in origin precluded an accurate classification. CONCLUSION: FNAB
      of pancreatic cystic lesions can differentiate mucinous from nonmucinous
      pancreatic cysts and provide definitive evidence of malignancy. In some cases,
      serous cystadenomas can be diagnosed. Pseudocysts can be suspected on the basis
      of an inflammatory smear lacking both epithelial cells and background mucin, but
      this finding is not specific. Nonpancreatic lesions constitute a significant
      percentage of cases aspirated as pancreatic cysts and present a major pitfall in
      cytologic interpretation.

PMID- 9250288
TI  - Fine needle aspiration biopsy vs. ultrasound-guided transrectal random core
      biopsy of the prostate. Comparative investigations in 246 cases.
AB  - OBJECTIVE: To compare fine needle aspiration biopsy (FNAB) and ultrasound-guided
      transrectal core biopsy of the prostate. STUDY DESIGN: FNAB and the random core
      biopsy were performed simultaneously on 246 patients who either had striking
      palpable signs or increased levels of prostate-specific antigen, at least 5
      micrograms/mL, on two separate examinations over a six-week period, RESULTS: The
      histologic and cytologic evaluations showed very close conformity between the two
      methods. Fifty-eight percent of the patients had benign prostate hyperplasia. Of
      the total number of patients, 103 (42%) had prostate carcinoma. This figure was
      confirmed in 101 (98%) of cases using FNAB. In two cases (0.8%) atypical prostate
      hyperplasia was diagnosed. In five cases the examination had to be repeated since
      insufficient prostate cell material was collected. Ultrasound-guided random core
      biopsy showed the presence of carcinoma in 96 of 103 patients (93%). It was
      necessary to repeat the examination in one patient due to a lack of adequate cell
      material. CONCLUSION: In our hands, FNAB method has a sensitivity of 98%, whereas
      core biopsy attained 91%. Both methods showed 100% concurrence in specificity.

PMID- 9250289
TI  - Accuracy of fine needle aspiration in distinguishing subtypes of renal cell
      carcinoma.
AB  - OBJECTIVE: To evaluate the cytologic features of each subtype of renal cell
      carcinoma (RCC) for separating the various subtypes. STUDY DESIGN: Thirty-eight
      renal fine needle aspiration (FNA) specimens with surgical resection follow-up
      were retrospectively reviewed and classified without knowledge of the resection
      specimen diagnosis. These included 18 clear cell RCCs, 8 papillary RCCs, 4
      oncocytomas, 2 chromophobe RCCs, 2 sarcomatoid RCCs and 4 metastases to the
      kidney. RESULTS: Seventy-four percent of the primary renal lesions were correctly
      classified. All 4 oncocytomas and the 2 chromophobe tumors were correctly
      classified, while both sarcomatoid RCCs and 3 of 8 papillary RCCs were
      misclassified as clear cell RCC. One clear cell RCC was misclassified as
      papillary type. Two clear cell and one papillary RCC were nondiagnostic; in each
      case the tumor had a prominent cystic component. All four metastases were
      correctly identified. CONCLUSION: Subclassification of RCC by FNA is relatively
      accurate. In this study, the most common error was to misclassify papillary and
      sarcomatoid RCC as clear cell RCC.

PMID- 9250290
TI  - Intracytoplasmic eosinophilic inclusions (Melamed-Wolinska bodies). Association
      with metastatic transitional cell carcinoma in pleural fluid.
AB  - OBJECTIVE: To determine if eosinophilic cytoplasmic inclusions (Melamed-Wolinska
      bodies) (ECIs) can help to distinguish metastatic transitional cell carcinoma
      (TCC) from pulmonary carcinoma (PC) in pleural effusions. STUDY DESIGN: The
      presence of ECIs was evaluated in malignant pleural effusions from 8 cases (5
      patients) of TCC and 38 cases of pulmonary carcinoma (PC). ECIs were categorized
      as absent, rare (< 2 per case), occasional (2 per case to < 1 per high-power
      field), frequent (1-2 per high-power field) or numerous (> 2 per high-power
      field). RESULTS: In pleural fluids with TCC, ECIs were numerous in 1 case,
      frequent in 2 cases, occasional in 3 cases and absent in 2 cases. In contrast, in
      pleural fluids with PC, ECIs were occasional in 1 case, rare in 5 cases and
      absent in 32 cases. CONCLUSION: While not present in every case, frequent ECIs in
      a malignant pleural effusion are suggestive of TCC rather than PC.

PMID- 9250291
TI  - Cercariform cells for helping distinguish transitional cell carcinoma from non
      small cell lung carcinoma in fine needle aspirates.
AB  - OBJECTIVE: To determine if cercariform cells, a recently described finding in
      transitional cell carcinomas (TCC), can aid in distinguishing fine needle
      aspirates (FNA) of TCC from non-small cell lung carcinoma (NSCLC). STUDY DESIGN:
      We compared the incidence of cercariform cells in FNAs of 14 cases of TCC with 22
      cases of NSCLC. RESULTS: Cercariform cells were identified in 8/14 (57%) cases of
      TCC as compared with 3/22 (14%) cases of NSCLC. Cercariform cells were often
      present and abundant (> 10 per case) in cases of TCC without squamous
      differentiation (8/9) but were not present in TCCs with extensive squamous
      differentiation (0/5). In NSCLCs, cercariform cells were rare (< 10 per case),
      and the cytoplasmic borders were sometimes not as well defined. The number of
      cercariform cells was significantly higher in FNAs of TCC without squamous
      differentiation than in FNAs of NSCLCs (P < .001). CONCLUSION: The presence of
      numerous cercariform cells in an FNA favors TCC over NSCLC.

PMID- 9250292
TI  - Comparative cytology of the oral cavities of snuff users.
AB  - OBJECTIVE: To determine the effects of smokeless tobacco (snuff) on the
      epithelium of the oral cavity. STUDY DESIGN: Cytologic smears were taken from the
      oral cavities of 22 snuff users and 19 control subjects. The samples were stained
      with the Papanicolaou method and accessed for cellularity, anucleated cells,
      micronuclei and broken egg nuclei. RESULTS: An average of 7,624 cells per slide
      were found in the user group and 1,348 in the control. An average of 3,619
      (47.5%) anucleated cells in the user group and 33.1 (2.5%) in the control were
      found per slide. Users with lesions had a significantly higher rate of
      anucleation than those without lesions. A total of 216 micronuclei were found in
      the user group and 46 in the control group. The broken egg nucleus was commonly
      found in both groups. The broken egg phenomenon is described as a nucleus that is
      in two portions and connected by a thin band of Feulgen-negative material.
      CONCLUSION: The regular use of snuff causes loss of cell cohesion, hyperkeratosis
      and an increased incidence of micronuclei. The relationship of these conditions
      to the development of oral cancer is unclear. The most likely anomaly that may be
      associated with carcinogenesis is the micronucleus.

PMID- 9250293
TI  - Uncommon tumors of the salivary gland in fine needle aspiration biopsies. A
      surgeon's perspective.
AB  - OBJECTIVE: To determine the utilization of fine needle aspiration (FNA) biopsy in
      guiding the surgeon in the management of patients with parotid masses and to
      study the cytohistologic correlations of rare parotid tumors. STUDY DESIGN: FNA
      biopsies and parotidectomies performed by a head-and-neck surgeon over an
      approximate three-year period were analyzed. Cytologic features of rare salivary
      gland tumors were also studied and correlated with their histology. RESULTS: In
      an acinic cell carcinoma in a 15-year-old female whose smears were stained with
      Diff-Quik, novel negative images of crystals were found intracytoplasmically and
      extracellularly, corresponding to the crystallized, membrane-bound, exocrine,
      secretory substance ultrastructurally. A truly malignant mixed tumor from a 73
      year-old female showed capsular invasion in the primary site that later
      metastasized to the lung with both epithelial and mesenchymal components. The
      tumor cells did not exhibit nuclear atypia except for fine cytoplasmic vacuoles
      in the Diff-Quik-stained smears. Basal cell adenoma, membranous (dermal analogue)
      type, from an 87-year-old female had an interesting geographic pattern on smears.
      CONCLUSION: Within three years, a total of 70 FNAs were performed. Of those
      cases, 46 had surgery. Preoperative FNAs of the salivary gland lesions were
      utilized by the surgeon in guiding treatment options for large, fixed masses as
      well as masses < 1 cm, in elderly and acquired immunodeficiency syndrome
      patients.

PMID- 9250294
TI  - Fine needle aspiration biopsy findings in lymphoepithelial carcinoma of salivary
      gland.
AB  - OBJECTIVE: To study the fine needle aspiration cytology of lymphoepithelial
      carcinoma of salivary gland (LECSG). STUDY DESIGN: Needle aspirates from five
      primary and two metastatic LECSGs were reviewed. RESULTS: Three aspirates showed
      very scant cellularity with rare tumor cells originally misinterpreted as
      lymphohistiocytic cells. Six fine needle aspiration biopsies (FNABs) contained
      medium to large polygonal and spindled cells with one or more prominent nucleoli.
      Five aspirates also displayed a heterogeneous population of lymphoid cells, while
      a sixth had much necrotic debris and only a few lymphocytes admixed with tumor
      cells. CONCLUSION: In the clinical setting of an Inuit or Chinese patient with a
      salivary gland mass, an FNAB with these features should suggest the possibility
      of LECSG.

PMID- 9250295
TI  - Fine needle aspiration cytodiagnosis of toxoplasmic lymphadenitis.
AB  - OBJECTIVE: To study six cases of toxoplasmic lymphadenitis in which the diagnosis
      was made by fine needle aspiration cytology and confirmed by subsequent serology.
      STUDY DESIGN: For cytologic study the material was received as needle and syringe
      washings, air-dried smears and alcohol-fixed smears, which were prepared and
      appropriately stained. Additionally, cell blocks were made, processed, cut and
      stained. RESULTS: The cytohistologic features were characterized by a
      polymorphous population of cells, germinal centers, a few epithelioid-type cells
      and histiocytes with intracellular organisms resembling Toxoplasma gondii.
      Serologic testing for toxoplasma in all the cases revealed elevated titers.
      CONCLUSION: Lymphadenitis due to Toxoplasma infection is common and should be
      considered in the diagnosis of unexplained lymphadenopathy at all sites,
      especially the cervical region. Serologic confirmation should be recommended for
      all suspected cases of this self-limited condition, for which no treatment is
      necessary. Fine needle aspiration cytodiagnosis can eliminate the need for
      hospitalization and surgery.

PMID- 9250297
TI  - Cytologic diagnosis of anaplastic large cell lymphoma.
AB  - OBJECTIVE: To identify characteristic cytomorphologic and immunocytochemical
      features of anaplastic large cell lymphoma (ALCL). STUDY DESIGN: We reviewed all
      positive cytology cases from patients with histologically confirmed ALCL at the
      National Institutes of Health/National Cancer Institute for patient demographics,
      cytologic appearance and, when available, immunocytochemical staining pattern
      with markers for CD30, CD3, L26, CD15, leukocyte common antigen and epithelial
      membrane antigen (EMA). RESULTS: Twenty-one cases were reviewed from seven
      patients (four males and three females) aged 2-83 years; 2 were human
      immunodeficiency virus positive. Specimens included exfoliative (cerebrospinal
      fluid, pleural fluid) and aspirated material (lymph node, lung, soft tissue).
      Commonly noted morphologic features included a smear pattern of largely dispersed
      cells with focal aggregates; variability in cell size with smaller and larger
      multinucleated giant forms (average cell size 42 microm); eccentric, round to
      oval nuclei; prominent nucleoli; a "ropy" chromatin pattern; and deeply
      basophilic, variably vacuolated cytoplasm. Necrosis was frequent. A proteinaceous
      background was prominent in cellular samples. Lymphoglandular bodies and lymphoid
      tangles were not prominent. Of cases evaluated immunocytochemically, 100% were
      positive for CD30, and 75% showed EMA positivity. Expression of other markers was
      variable. CONCLUSION: ALCL has a distinct cytomorphologic appearance and
      immunocytochemical staining pattern such that a reliable diagnosis can be made on
      cytologic material.

PMID- 9250298
TI  - Clinical significance of an inconclusive cytopathologic diagnosis: a five-year
      experience at Duke University Medical Center. II. Analysis and follow-up of
      specimens from the respiratory tract.
AB  - OBJECTIVE: As a follow-up of our initial report, we critically examined a
      selected number of cases from the respiratory tract with an original diagnosis of
      "atypical cells present suspicious for malignancy" in order to ascertain if any
      particular features of the specimen or the atypical cells were predictors of
      malignancy. STUDY DESIGN: From a total of 563 such cases, 31 were identified with
      subsequent histologic findings of a nonneoplastic pathologic process. An
      additional 45 cytologic cases were randomly selected to represent those with
      subsequent histologic findings confirming the suspicion of malignancy. All the
      cytologic specimens were examined without knowledge of the histologic follow-up
      results. RESULTS: Analysis of the cellular composition of the specimens
      identified no discernible difference between specimens from benign and malignant
      processes. Quantitative analysis of the atypical cells and qualitative assessment
      of the nuclear abnormalities revealed that marked nuclear hyperchromasia and a
      very high nuclear/cytoplasmic ratio were more likely to represent a malignant
      process. However, none of the parameters examined could consistently predict the
      presence or absence of malignancy. CONCLUSION: When a single cytologic specimen
      is inconclusive as to the presence or absence of malignancy, standard cytologic
      criteria cannot reliably predict a malignant process.

PMID- 9250296
TI  - Small round cell tumors of the abdomen and thorax. Role of fine needle aspiration
      cytologic features in the diagnosis and differential diagnosis.
AB  - OBJECTIVE: To evaluate the role of cytomorphologic features in the diagnosis and
      differential diagnosis of small round cell tumor (SRCT) of the abdomen and
      thorax. STUDY DESIGN: During a period of six years (1985-1990), ultrasound/
      computed tomography-guided fine needle aspiration cytology was performed on
      thoracic and abdominal/ pelvic masses in 899 cases. Slides were not available for
      review in 28 cases. Review of smears by one of the investigators (D.K.D.) in the
      remaining cases, which included 239 with intrathoracic and 632 with
      intraabdominal/pelvic masses, yielded 380 (43.6%) cases of malignancy. Of these,
      71 (18.7%) cases were small round cell tumors. In 59 cases of SRCT the smears
      were found suitable for detailed assessment of cytomorphologic features. RESULTS:
      The 59 cases of small round cell tumors included 5 cases of neuroblastoma, 7 of
      hepatoblastoma, 4 of nephroblastoma, 1 of pulmonary blastoma, 2 of Ewing's
      sarcoma, 23 of non-Hodgkin's lymphoma (NHL), 15 of small cell anaplastic
      carcinoma (SCAC), 1 NHL/SCAC and 1 small round cell tumor (not otherwise
      specified). The frequencies of rosettes (60%) and filamentous/fibrillar matrix
      (100%) in neuroblastoma; acinar formation in hepatoblastoma (100%) and SCAC
      (93.3%); tubule formation in nephroblastoma (100%); lipid vacuoles (69.6%),
      exclusive noncohesive cells (95.7%) and lymphoglandular bodies (87%) in NHL; and
      nuclear molding (100%) and paranuclear blue inclusions (60%) in SCAC were
      significantly higher as compared to the rest of the SRCTs (P < .01 to < .0001).
      CONCLUSION: The various cytomorphologic features, alone or in conjunction with
      other cytologic features, and clinical/imaging findings are very useful in the
      diagnosis of specific types of SRCT.

PMID- 9250299
TI  - Evaluation of the PAPNET system for prescreening triage of cervicovaginal smears.
AB  - OBJECTIVE: To assess the PAPNET System for prescreening triage of cervical
      smears. STUDY DESIGN: We prospectively prescreened 5,170 consecutive
      cervicovaginal smears with the PAPNET System. The slides were then manually
      screened by cytotechnologists blinded to the PAPNET diagnoses. Cases identified
      as abnormal by either PAPNET or manual screening were reviewed by a
      cytopathologist. The PAPNET and manual diagnoses were correlated. RESULTS:
      Diagnostic concordance between PAPNET and manual screening was seen in 4,340
      (84%) of the cases (3,167 negative, 1,038 abnormal and 135 unsatisfactory).
      Noncorrelation between PAPNET and manual diagnosis occurred in 794 cases (543
      abnormal by PAPNET and negative manually, 228 negative by PAPNET and abnormal
      manually, 8 abnormal by PAPNET and unsatisfactory manually, 29 unsatisfactory by
      PAPNET and negative manually, 7 negative by PAPNET and unsatisfactory manually).
      The diagnostic sensitivity of the PAPNET System was 82%, diagnostic specificity
      85%, predictive value of a positive test 66% and predictive value of a negative
      test 93.4%. The false negative fraction of PAPNET was 6.4% for low grade squamous
      intraepithelial lesion and above. CONCLUSION: PAPNET performed effectively for
      prescreening triage, increasing the accuracy of screening and reducing the
      screening time.

PMID- 9250300
TI  - Atypical squamous cells of undetermined significance. Stratification of the risk
      of association with, or progression to, squamous intraepithelial lesions based on
      morphologic subcategorization.
AB  - OBJECTIVE: To analyze follow-up data on atypical squamous cells of undetermined
      significance (ASCUS) based on morphologic characteristics. STUDY DESIGN: Five
      years of follow-up was obtained on a cohort of 437 consecutive patients from 1986
      who had initial diagnoses of ASCUS, with a further categorization of type based
      on the maturity of the atypical cells. All such categorizations were made on the
      basis of specific cytologic criteria. Follow-up cytology and/or biopsy was
      available on 366 patients. RESULTS: During the follow-up period, 40 patients
      (13.5%) with ASCUS were diagnosed as having a squamous intraepithelial lesion
      (SIL); 15 (5%) were interpreted as high grade. When stratified by type of ASCUS
      based on cellular maturity, the following association/progression rates were
      noted: mature ASCUS, 10%; metaplastic ASCUS, 24%; and immature metaplastic ASCUS,
      42%. In metaplastic and immature metaplastic ASCUS cases, high grade SIL
      accounted for 42% and 60% of those subsequently diagnosed with a squamous
      intraepithelial lesion, respectively, versus 30% for mature ASCUS. CONCLUSION:
      With well-defined and consistent criteria for the diagnosis of the variety of
      "squamous atypias," a stratification of risk of progression to or association
      with SIL can be made. When features of metaplasia and immature metaplasia are
      noted in the cells of ASCUS, patients were observed to be at increasingly greater
      risk for the detection of SIL; those cases were proportionately more likely to be
      high grade.

PMID- 9250301
TI  - Atypical squamous cells of undetermined significance in the pediatric population.
      Implications for management and comparison with the adult population.
AB  - OBJECTIVE: To determine the significance of an atypical squamous cells of
      undetermined significance (ASCUS) diagnosis in patients 18 years or younger.
      STUDY DESIGN: From June 1994 to June 1995, 630 cervicovaginal smears were
      performed on patients 18 years or younger (mean age 16.4, range 14-18) at
      University Hospitals of Cleveland. Of these patients, 69 (10.9%) were diagnosed
      with ASCUS or ASCUS with a qualifying statement. Follow-up cervicovaginal smears,
      biopsies and charts were reviewed for a 12-18-month period following the initial
      diagnosis of ASCUS. RESULTS: The study population was sexually active: 63% were
      gravid, 21% were multigravid, 68% had a history of sexually transmitted diseases
      (STDs), and 32% had multiple STDs. Follow-up cervicovaginal smears or biopsies
      were obtained on 46 patients (32 cervicovaginal smears and 14
      biopsies/endocervical curettage cases). Mild to moderate dysplasia was identified
      in 21.6% of patients (10.8% on cervicovaginal smears and 10.8% on biopsies), and
      a repeat diagnosis of ASCUS was given in 37%. In patients with a repeat diagnosis
      of ASCUS, a follow-up cervicovaginal smear or biopsy revealed dysplasia in an
      additional 13%. The overall rate of dysplasia was 34.7%. CONCLUSION: Regardless
      of age, the diagnosis of ASCUS in a sexually active patient population has
      significant implications. Furthermore, we recommend that these patients be
      managed the same way as high-risk adult patients.

PMID- 9250302
TI  - Cytomorphologic evidence of human papillomavirus infection in smears from the
      irradiated uterine cervix.
AB  - OBJECTIVE: To report the cytomorphologic evidence of human papillomavirus (HPV)
      infection in cervical smears from women treated with radiotherapy for carcinoma
      of the uterine cervix. STUDY DESIGN: From January 1986 to December 1993, 32
      cervical cytologic smears (CCSs) from women who had received radiotherapy (Rtx)
      for squamous cell cervical carcinoma at A.C. Camargo Cancer Hospital were
      selected for study due to the presence of signs of HPV infection. Review of the
      files of these patients showed 22 additional samples, which we included in this
      study. The avidinbiotin-immunoperoxidase technique was performed on previously
      stained slides using polyclonal rabbit antibovine papillomavirus type 1 to
      confirm the HPV infection. RESULTS: Positive reactions were found in 18 cases (27
      samples), mainly in cells with classic koilocytotic features, but also in
      epithelial cells that lacked cytopathic effects. Only one case, a biopsy from a
      verrucous lesion observed after Rtx, was found to be positive for HPV 6/11 DNA by
      in situ hybridization. CONCLUSION: Cytologic and immunohistochemical positivity
      for HPV, as well as the reaction with a HPV 6/11 DNA probe, strongly suggested
      that HPV infection was acquired or expressed after radiotherapy. Further studies
      are needed to assess the mechanisms responsible for such an association.

PMID- 9250303
TI  - Quality assurance in cytology. Rescreening of previously negative smears from
      high grade squamous intraepithelial lesions.
AB  - OBJECTIVE: To determine the problem areas in the cytologic diagnosis of high
      grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia
      [CIN] 3). STUDY DESIGN: Previously negative smears from cases with histologically
      proven CIN 3 in 1988 and 1992 were reviewed for any discrepancies between the
      original and reviewed diagnoses. Such features as the presence of excessive
      inflammation, blood or bacteria, and atypical and dysplastic cellular changes
      were assessed. Original and reviewed reports for both years were compared, and
      the false negative rate was calculated. RESULTS: In the 1992 study, small numbers
      of abnormal cells, abnormal cells masked by inflammation and pale-staining HSIL
      were the common patterns when the diagnosis of HSIL was initially overlooked. In
      the 1988 study, the abnormal cells were overlooked mainly because of suboptimal
      smears. CONCLUSION: Determining cytologic patterns that pose problems in the
      diagnosis of HSIL is a valuable quality assurance procedure used in our
      laboratory. In performing these studies, we are able to pinpoint problem areas
      and educate our staff so as to minimize the number of false negative smears.

PMID- 9250304
TI  - Effects of dilute acetic acid on the cervical smear.
AB  - OBJECTIVE: To evaluate the effect of 5% acetic acid on the cells and cellular
      content of cervical smears. STUDY DESIGN: A randomized, controlled trial was
      performed with 42 patients in each group. The study group received acetic acid
      application to the cervix followed by a smear, while the sequence was reversed in
      the control group. Cytologic evaluation of the smears was done without knowledge
      of the group allocation in each case. RESULTS: The group in which acetic acid was
      applied before the smear was taken showed significantly poorer staining
      properties of the smear (P < .0001) and also significantly lower cellular content
      (P = .0006). CONCLUSION: Acetic acid has adverse effects on the cervical smear
      and should be applied after the smear is taken.

PMID- 9250305
TI  - Criteria for differential diagnosis of complex hyperplasia or beyond in
      endometrial cytology.
AB  - OBJECTIVE: To establish qualitative criteria for diagnosing complex hyperplasia,
      complex atypical hyperplasia and well-differentiated adenocarcinoma in
      endometrial cytology. STUDY DESIGN: The frequency of appearance of papillary and
      arborescent cell clusters and the morphology of type A stromal bundles in
      arborescent cell clusters were examined in 59 samples of complex hyperplasia, 23
      of complex atypical hyperplasia, 77 of well-differentiated adenocarcinoma and 40
      of normal endometrium. RESULTS: Papillary cell clusters were observed in all
      samples of hyperplasia and adenocarcinoma. The rate of observation of arborescent
      cell clusters increased proportionately to the progress from complex hyperplasia
      to complex atypical hyperplasia to well-differentiated adenocarcinoma. No
      arborescent cell clusters were found in normal endometrium. Primary branching and
      the number of layers of type A stromal bundles also increased with the progress
      toward complex hyperplasia and well-differentiated adenocarcinoma. Secondary and
      further branching was observed in large numbers in cases of adenocarcinoma.
      CONCLUSION: For detection of complex hyperplasia or lesions beyond it in
      endometrial cytology, it is important to observe the presence of papillary
      clusters. For differentiation of the various lesions, it is important to observe
      the presence of arborescent clusters as well as type A stromata inside the
      clusters.

PMID- 9250306
TI  - Cervical cancer screening in Japan. A case-control study.
AB  - OBJECTIVE: To prove the effectiveness of mass screening for cervical cancer with
      the cervical cytologic smear in Japan. STUDY DESIGN: The cases consisted of 109
      patients with invasive carcinoma who were identified by mass screening for
      cervical cancer between 1984 and 1989. For each case, two age-matched controls
      were chosen from females who underwent mass screening in the same district during
      the same period. The odds ratio (OR) for invasive cervical cancer and that of
      each histologic type for the previously screened vs. unscreened females were
      calculated. In addition, the OR for invasive cervical cancer according to the
      screening interval was calculated. RESULTS: The OR of invasive cervical cancer
      for the previously screened vs. unscreened females was significant (P < .16).
      According to the histologic type, the OR of squamous cell carcinoma for the
      previously screened vs. unscreened females was significant (P < .14), while that
      for adenocarcinoma was not significant (P < .45). According to screening
      interval, the OR for screening at a one- or two-year interval was significant (P
      < .11 and .33, respectively). CONCLUSION: This case-control study statistically
      showed the usefulness of screening for cervical cancer in Japan.

PMID- 9250307
TI  - Cytologic nuclear grade of malignant breast aspirates as a predictor of
      histologic grade. Light microscopy and image analysis characteristics.
AB  - OBJECTIVE: To determine if cytologic nuclear grade characteristics combined with
      image analysis assessment of morphometric nuclear parameters (1) correlate with
      the modified Scarff-Bloom-Richardson grading system and (2) discriminate between
      low and high nuclear grades of invasive ductal carcinoma. STUDY DESIGN: Fifty
      four fine needle aspiration biopsies (FNABs) of breast carcinoma were evaluated
      for five morphologic nuclear grade characteristics. In addition, four
      morphometric, standardized object measurements were analyzed by an image analysis
      system. Corresponding biopsies of invasive ductal carcinoma (46 cases) were
      independently evaluated with the Scarff-Bloom-Richardson grading system, modified
      into low (scores 3-6) and high (scores 7-9) grades. RESULTS: An overall agreement
      of 82% was reached by three of four cytopathologists for each of five morphologic
      characteristics. There was a strong correlation (r = .8059, P < .0001) between
      cytologic nuclear grade and modified histologic grade. Only pleomorphism,
      nucleoli and sum optical density retained their statistical significance in
      distinguishing low from high grade ductal carcinomas. These three characteristics
      also had the strongest correlation with cytologic nuclear grade. CONCLUSION:
      Cytologic nuclear grade from aspirates of ductal carcinoma can be a predictor of
      the modified histologic grades of Scarff, Bloom and Richardson. Nuclear
      morphology reinforced by image morphometry may separate these tumors into low and
      high nuclear grade categories.

PMID- 9250308
TI  - Cytology of "significant" breast ductal proliferations.
AB  - OBJECTIVE: To determine the usefulness of fine needle aspiration cytology in
      diagnosing breast ductal proliferations that fall short of invasive cancer
      (hyperplasia, atypia and in situ carcinoma). STUDY DESIGN: This study was a
      comparison of the cytomorphology and histomorphology of 30 palpable breast
      lesions in which an initial fine needle aspiration diagnosis of ductal
      hyperplasia or atypia was based on available criteria. RESULTS: Among six
      patients, a cytologic diagnosis of mild hyperplasia, based on monolayered cell
      sheets, was confirmed in five. Fourteen cytologic reports of moderate
      hyperplasia, based on three-dimensional cell clusters, cell overlap and
      sublumens, were confirmed in 12. A cytomorphologic diagnosis of atypical ductal
      hyperplasia was rejected in four of seven patients. Three cases of marked
      cytologic atypia were diagnosed histopathologically as ductal carcinoma in situ.
      CONCLUSION: In breast aspirates, three-dimensional ductal cell clusters, a
      swirling pattern of growth, sublumens, cell dyscohesion and conspicuous nuclear
      overlap indicate moderate ductal hyperplasia. Ductal atypia should be diagnosed
      only on such nuclear features as anisonucleosis, irregular nuclear membranes,
      clumped chromatin and eosinophilic macronucleoli. Cytologists should highlight
      those features which are important to diagnose breast proliferations as
      "significant" from the viewpoint of progressing to invasive cancer and not
      attempt too fine a classification of these lesions.

PMID- 9250309
TI  - Fine needle aspiration biopsy of breast carcinoma in pregnancy and lactation.
AB  - OBJECTIVE: To delineate the cytomorphologic features seen in cancer of the breast
      during pregnancy and lactation, to compare them to the cytomorphologic parameters
      in benign conditions and to determine the feasibility of differentiating features
      of malignant breast carcinoma from those of benign breast lesions during
      pregnancy. STUDY DESIGN: The study group consisted of pregnant or lactating women
      with breast carcinoma and with benign breast lesions who underwent fine needle
      aspiration (FNA) of the breast lesions. The findings of FNA were reviewed,
      analyzed, tabulated and correlated with the pathologic diagnosis of the breast
      biopsies. RESULTS: Eleven patients had malignant cytomorphologic changes,
      including increased cellularity, multilayering, enlarged and pleomorphic nuclei,
      single or multiple nucleoli, mitosis and numerous isolated tumor cells. Secretory
      changes were scanty. The background was foamy and necrotic. FNA of the benign
      lesions showed a biphasic cell pattern with cohesion; minimal nuclear
      pleomorphism; single, regular nucleoli; and naked nuclei in a granular background
      with foamy macrophages. Increased cellularity with nuclear atypia, single cells
      and a dirty background was seen in benign and malignant conditions. CONCLUSION:
      The main cytologic features that differentiate breast carcinoma from benign
      conditions during pregnancy and lactation are crowding and overlapping of nuclei,
      dyscohesion and enlarged, pleomorphic nuclei with irregular nuclear membranes,
      coarse nuclear chromatin and mitoses. Pregnancy-related hyperplastic changes with
      atypia can potentially result in a false positive diagnosis of carcinoma.

PMID- 9250310
TI  - Fine needle aspiration cytology of palpable breast lesions. Histologic subtype in
      false negative cases.
AB  - OBJECTIVE: To evaluate the use of fine needle aspiration cytology (FNAC) in the
      management of benign and malignant breast disease in an outpatient breast clinic
      and to determine the guidelines for reporting on FNAC of breast lesions, we
      evaluated the test results in correlation with the histologic diagnosis. STUDY
      DESIGN: We evaluate the test results of 669 cases of FNAC of the breast in 17
      months in our outpatient breast clinic in correlation with the histologic
      diagnosis, histologic subtype according to the Japan Mammary Cancer Society
      classification and mammography results in false negative cases. RESULTS: Among
      669 cases, 25.3% were inadequate for cytologic diagnosis. An analysis of the
      results using the two-by-four contingency table, including cases with inadequate
      cytologic diagnosis, showed that 10.6% and 1.0% had false negative and false
      positive cytologic diagnoses, respectively; sensitivity and specificity were
      76.9% and 91.6%, respectively. The false negative rate of 10.6% was higher than
      expected, and those belonged mostly to the "inadequate" cytologic diagnosis
      category even though they were discrete, obviously malignant masses clinically.
      To try to explain this, we compared the cytologic results and histologic subtype
      according to the Japan Mammary Cancer Society classification and the mammography
      results. Of 73 cases of infiltrating ductal carcinoma in which retrospective
      reexamination of the histology slide was possible, 27 (37.0%) were papillo
      tubular type, 11 (15.1%) were solid-tubular type and 35 cases (47.9%) were
      scirrhous type. Although the scirrhous subtype was only 37.0% in the group in
      which a cytologic diagnosis of carcinoma was possible, more than two-thirds of
      the cases of false negative cytology were scirrhous type and had malignant
      mammographic findings. This finding was statistically significant. CONCLUSION: In
      cases of ductal carcinoma of scirrhous subtype, the FNAC tended to be inadequate
      and false negative, but mammography showed better discrimination in such cases.

PMID- 9250311
TI  - Fine needle aspiration cytology of tubular carcinoma of the breast.
AB  - OBJECTIVE: To analyze six cases of tubular carcinoma involving the breast in
      which the diagnosis was made by fine needle aspiration cytology (FNAC). STUDY
      DESIGN: All patients were females between the ages of 28 and 67 years. The
      aspiration findings were confirmed by subsequent cell blocks of the aspirates and
      tissue examination of the breast mass. The aspirate was obtained using multiple
      passes in the breast masses while maintaining negative pressure. RESULTS: The
      cytohistologic features in all cases were characterized by a bland and orderly
      appearance of cells, few cell atypias, variable numbers of myoepithelial cells,
      tubular structures and somewhat angular epithelial clusters. The value of
      immunocytochemical study in the diagnosis was uncertain. CONCLUSION: The uncommon
      occurrence of tubular carcinoma of the breast, the bland and orderly appearances
      of cells in FNAC samples (as in tissue) and the difficulties in the cytodiagnosis
      can be found in other breast conditions. A cautious attitude toward the diagnosis
      of tubular carcinoma from FNAC samples is necessary, and cell atypias, when seen,
      should be reported with a recommendation for removal of the breast lump for
      detailed tissue examination.

PMID- 9250312
TI  - Imprint cytology in the diagnosis of Helicobacter pylori infection.
AB  - OBJECTIVE: To evaluate if imprint cytology yields the same results as brushing
      cytology. STUDY DESIGN: Brushing and imprint cytology of the antral mucosa were
      obtained from 20 unselected patients referred for upper endoscopy and evaluated
      by two experienced cytologists. Concordance in the identification of Helicobacter
      pylori with both techniques was assessed. RESULTS: In the presence or absence of
      H pylori, 100% concordance between both techniques was found. CONCLUSION: Both
      techniques yield the same sensitivity for identifying H pylori. Imprint cytology
      is easier to perform and overcomes most of the problems of brushing cytology.

PMID- 9250313
TI  - pCEA canalicular immunostaining in fine needle aspiration biopsy diagnosis of
      hepatocellular carcinoma.
AB  - OBJECTIVE: To assess the usefulness of bile canalicular polyclonal
      carcinoembryonic antigen (pCEA) immunostaining in fine needle aspiration biopsy
      (FNAB) diagnosis of hepatocellular carcinoma (HCC). STUDY DESIGN: Hepatic FNAB
      with cell blocks of 72 confirmed and 6 possible HCC and 23 non-HCC malignancies
      (controls) were analyzed. Sections were stained with antibody to pCEA using the
      streptavidin biotin-immunoperoxidase method and results correlated with tumor
      grade and other parameters used in HCC diagnosis. RESULTS: Canalicular pCEA
      staining was observed in 60 (83%) of the 72 HCC. This category comprised 29%,
      31%, 36% and 4% grade 1-4 tumors, including 7 small cell, 4 clear cell and 1
      giant cell variants. With increasing anaplasia, the canaliculi became infrequent,
      irregularly distributed, and increasingly distorted and interrupted. Canalicular
      staining helped distinguish clear and small cell variants from metastatic renal
      cell carcinomas and neuroendocrine tumors, respectively. Of the six problematic
      cases, one was confirmed to be HCC with plasmacytoid features and five to be
      adenocarcinomas, of which three could have been combined hepatocellular
      cholangiocarcinomas. Liver cell dysplasia also displayed an abnormal canalicular
      pattern. No cytoplasmic staining was seen in pure HCC. CONCLUSION: pCEA
      immunostaining cannot separate malignant, dysplastic or benign hepatocytes. It is
      usually not required in cytodiagnosis of most HCC. However, it is most helpful in
      confirming atypical variants of HCC, which may mimic other tumors.

PMID- 9250314
TI  - A method of teaching fine needle aspiration biopsy of the thyroid gland.
AB  - OBJECTIVE: To design an in vitro method of teaching the technique of fine needle
      aspiration biopsy of the thyroid gland. STUDY DESIGN: A "resuscitation" manikin
      is used to simulate an adult patient and a thyroid gland is placed on the
      manikin. RESULTS: The gland can be examined and aspirated. Subsequent microscopic
      evaluation permits the correlation of aspiration technique and specimen adequacy.
      CONCLUSION: This in vitro method should shorten the learning process for a novice
      aspirator and may help reduce the rate of inadequate specimens.

PMID- 9250315
TI  - Cytologic diagnosis of complicated pulmonary unilocular cystic hydatidosis. A
      study of 131 cases.
AB  - OBJECTIVE: To determine the value of cytochemical stains and microscopic
      techniques for the detection of true hydatid elements (primary cytologic
      criteria) and to evaluate the efficacy of granulomatous elements (secondary
      cytologic criteria) for the diagnosis of complicated pulmonary unilocular cystic
      hydatidosis (CPUCH). STUDY DESIGN: Sputum, bronchial washing and bronchial
      brushing specimens obtained from 131 patients with a presumptive diagnosis of
      CPUCH were reviewed. RESULTS: CPUCH was histopathologically proven in 111 of 131
      patients. Scolices were found in 11 patients in Papanicolaou-EA65 (PAP-EA65)
      stained slides. Special stains and dark field microscopy (DFM) did not make any
      additional contribution to specifying the nature of the scolexlike objects.
      Hooklets were found in 26 patients in PAP-EA65-stained slides. Masson's trichrome
      stain and DFM revealed hooklets in 37 and 50 cases, respectively. Laminated
      membrane fragments were found in 14 patients in PAP-EA65-stained slides. Gomori's
      methenamine silver stain and DFM demonstrated laminated membrane fragments in 25
      and 33 cases, respectively. Secondary cytologic criteria, such as multinucleated
      giant cells, degenerated squamous cells, dyskaryotic squamous cells, excessive
      amounts of eosinophils, plasma cells, lymphocytes, histiocytes, necrotic debris,
      fibrinoid material and erythrocytes, were considered to be suggestive of hydatid
      disease when there are more than three such factors in patients with a
      presumptive diagnosis of CPUCH. CONCLUSION: Though DFM examination is superior to
      cytochemical stains used in this study, both cytochemical stains and DFM are
      useful in increasing the sensitivity of cytologic detection of true hydatid
      elements, especially hooklets and laminated membrane fragments. They should be
      used as auxiliary techniques. Secondary cytologic criteria are suggestive of the
      diagnosis of CPUCH, and special care should be taken when there are more than
      three such factors in cytologic specimens.

PMID- 9250316
TI  - Comparison of conventional cytologic smears and ThinPrep preparations from the
      anal canal.
AB  - OBJECTIVE: To compare anal cytology prepared via conventional methods and the
      ThinPrep processor. STUDY DESIGN: Cells from the anal canal were collected using
      a moistened swab. One hundred thirty-six samples were collected from 133 gay or
      bisexual men; 102 were human immunodeficiency virus seropositive. A conventional
      smear was prepared and fixed in 95% ethanol. The residual cells on the swab were
      collected for thin-layer preparation using the Cytyc processor. RESULTS: The
      diagnoses made from the conventional smears and thin layers agreed in 113 of 136
      cases. An additional 19 cases were classified within one diagnostic category of
      each other. Two cases of low grade squamous epithelial lesion (SIL) diagnosed on
      the ThinPrep were judged negative on the conventional smear. Similarly, two cases
      of low grade SIL diagnosed on the conventional smear were judged negative on the
      thin-layer preparations. Rectal columnar cells were present on 127 of the
      ThinPrep samples but on only 113 of the conventional smears. CONCLUSION: ThinPrep
      and conventional smears of the anal canal yielded similar diagnoses. Rectal
      columnar cells were more frequently encountered on the thin layers; their
      presence is an indication that the rectal transformation zone may have been
      adequately sampled. In addition, the ThinPrep technique reduces fecal and
      bacterial contamination and air-drying artifact, which frequently hinder
      cytologic evaluation of the anal canal.

PMID- 9250317
TI  - Use of Riu stain in the immediate interpretation of bronchial brushing cytology.
      Comparison with Papanicolaou stain and histology.
AB  - OBJECTIVE: To determine the usefulness of Riu stain in the immediate
      interpretation of cytologic material from bronchoscopic brushings and its
      accuracy in the diagnosis of lung malignancies. STUDY DESIGN: A prospectively
      comparative study between Riu and Papanicolaou stain with pathologic control was
      conducted. Eighty-six patients with central lung lesions, visible during
      fiberoptic bronchoscopy, were studied. Endobronchial biopsies and brushings were
      performed at the time of the same procedure. RESULTS: The diagnostic accuracy of
      Riu stain for malignancy was 97%, with a sensitivity of 99%, specificity of 85%,
      positive predictive value of 97% and negative predictive value of 92%. As for the
      Papanicolaou technique, the diagnostic accuracy for malignancy was 97%, with a
      sensitivity of 97%, specificity of 92%, positive predictive value of 99% and
      negative predictive value of 86%. The overall cytologic typing accuracy of Riu
      stain was 86%, which was comparable with that of Papanicolaou stain (90%, P =
      .48). Both techniques are more accurate in the diagnosis of squamous carcinoma,
      small cell carcinoma and adenocarcinoma than in large cell carcinoma. CONCLUSION:
      Riu stain is rapid, simple to use and, most important, accurate for the
      identification of lung malignancies. It can increase the diagnostic success rate,
      prevent unnecessary repeat bronchoscopies and lower related complications.

PMID- 9250318
TI  - A triple stain for the detection of Helicobacter pylori in gastric brushing
      cytology.
AB  - OBJECTIVE: Helicobacter pylori is a surface bacterium associated with gastritis.
      The triple stain (TS), combining silver, hematoxylin and eosin, and alcian blue
      at pH 2.5, is valuable in the detection of H pylori in tissue. We evaluated the
      usefulness of TS as compared with Papanicolaou stain in detecting H pylori in
      gastric brushings and biopsy specimens. STUDY DESIGN: Gastric brushings and
      biopsy specimens were obtained from 21 patients. The Papanicolaou-stained slides
      were restained with TS, and the brushings and biopsy specimens were independently
      evaluated by the authors. RESULTS: H pylori was found in 9 of 21 randomly
      selected cases using TS. Of these, two cases were positive on brushings alone and
      three on biopsy alone. Only three of the nine cases were positive by Papanicolaou
      stain. None of the 21 samples were positive with Papanicolaou stain yet negative
      with TS. Detection of H pylori was restricted to patients with gastric
      ulcerations but was not limited by paucity of glands. CONCLUSION: TS is useful
      for detecting H pylori in gastric brushings and provides excellent cytologic
      detail. Furthermore, TS is superior to Papanicolaou stain for H pylori detection
      and is a valuable adjunct to biopsy.

PMID- 9250319
TI  - Alcoholic carbowax prefixation and formal alcohol fixation. A new technique for
      urine cytology.
AB  - OBJECTIVE: To compare the cellular yield and sensitivity of cancer detection by
      urine cytology using alcoholic carbowax as a prefixative and formal alcohol as a
      final fixative with the conventional centrifugation-and-smearing method. STUDY
      DESIGN: Four hundred seventeen voided urine specimens were examined. Each
      specimen was divided into two equal portions. One portion was centrifuged and wet
      fixed (CS). The other was treated with alcoholic carbowax as a prefixative and
      then fixed in formal alcohol (CW). The smears were studied for cellular yield,
      morphology, cancer detection rate and typing. RESULTS: The CW method yielded
      significantly more cells with excellent morphology. It detected 25 more abnormal
      cases out of a total of 86, including 5 more transitional cell carcinomas, as
      compared to the CS method. This finding was statistically significant (P <
      .0000003). CONCLUSION: The CW method is simple and enhances cellular yield and
      the cancer detection rate as compared to the conventional centrifuge-and-smear
      technique.

PMID- 9250320
TI  - Blue cytoplasmic inclusions in a follicular neoplasm of the thyroid.

PMID- 9250321
TI  - Fine needle aspiration of primary angiosarcoma of bone.

PMID- 9250322
TI  - Malignant lymphoma identified on a cervical cytologic smear, with
      immunophenotypic analysis.

PMID- 9250323
TI  - Urethral carcinoma in a female.

PMID- 9250324
TI  - Lupus erythematosus cells in pleural effusions: diagnostic of systemic lupus
      erythematosus?

PMID- 9250325
TI  - Multiple myeloma presenting as a subcutaneous nodule on the chest wall: diagnosis
      by fine needle aspiration.

PMID- 9250326
TI  - Intracytoplasmic crystals of alveolar soft part sarcoma: demonstration by Riu's
      stain.

PMID- 9250327
TI  - Metastatic lobular carcinoma of the breast in a cervical-vaginal smear.

PMID- 9250328
TI  - Small cell neuroendocrine carcinoma: cytologic findings in a breast aspirate.

PMID- 9250329
TI  - Cytology of a fetal immature teratoma: intrauterine aspiration for prenatal
      diagnosis.

PMID- 9250330
TI  - Immunocytochemical diagnosis of Bellini duct carcinoma.

PMID- 9250331
TI  - CA-125 immunostaining in mesotheliomas.

PMID- 9250332
TI  - Solitary plasmacytoma of a cervical lymph node: regression after fine needle
      aspiration.

PMID- 9250333
TI  - Fine needles with echo markers: increasing cell dragging during biopsy.

PMID- 9250335
TI  - Toward a restructuring of the schools.

PMID- 9250334
TI  - Pigment-laden macrophages in ascitic fluid associated with melanosis coli.

PMID- 9250336
TI  - Model mental health programs and educational reform: introduction.

PMID- 9250337
TI  - The uneasy alliance of mental health services and the schools: an historical
      perspective.
AB  - School-based mental health and social welfare services have evolved over the past
      century to play important roles in the education of children and youth. Relations
      between schools (administrators, boards of education, teachers) and services
      (social workers, therapists, counselors) have generally been awkward-occasionally
      embracing and nurturing, at times competitive and distant. This article reviews
      the history of school mental health services, focusing on service goals, the
      nature of professional practice, and the forces that have prevented harmony.

PMID- 9250338
TI  - Implementing prevention programs in high-risk environments: application of the
      resiliency paradigm.
AB  - Little is known about what happens when validated model prevention programs are
      introduced into the schools, typically without systematic evaluation and with the
      assumption that they will have positive impact. This study examines the outcome
      of such initiatives in schools at "high risk" for program failure, identifies
      factors related to goal attainment in both high- and low-risk school districts,
      and suggests practices to guide implementation of successful prevention programs.

PMID- 9250339
TI  - Teacher consultation: impact on teachers' effectiveness and students' cognitive
      competence and achievement.
AB  - Teachers from six ethnically diverse inner-city schools participated in weekly
      mental health consultation for more than two years. Using a quasi-experimental
      design, a longitudinal sample of 91 teachers and 209 students was assessed
      periodically through multiple standardized measures. Results indicate that a low
      cost, indirect intervention had a direct impact on teachers' sense of
      professional competence and was linked to positive changes in students' sense of
      cognitive competence and their academic achievement.

PMID- 9250340
TI  - School-based wraparound planning: integrating services for students with
      emotional and behavioral needs.
AB  - The wraparound process for planning unique and flexible services emerged from
      community-based human-service programs for children and youth exhibiting serious
      emotional disturbance. The application of wraparound in schools is described and
      illustrated via examples of local, statewide, and national initiatives. These
      experiences suggest strategies that can improve the school's effectiveness in
      serving students with, or at risk of, emotional and behavioral challenges.

PMID- 9250341
TI  - Supporting children and families in the schools: the school of the 21st century.
AB  - The School of the 21st Century, a model designed to address the soaring need for
      child care, is housed in an institution already present in every neighborhood-the
      public school. Its potential to serve as a primary prevention program, through
      provision of child-care and family-support services for children from birth
      through age 12, is described. Examples of program effectiveness are offered, and
      the additional benefits of integration with related programs are outlined.

PMID- 9250342
TI  - Addressing barriers to learning: beyond school-linked services and full-service
      schools.
AB  - To enhance services in the schools, there are calls for coordination,
      integration, comprehensiveness, and other systemic reforms. These topics are
      explored from the perspective of the role of school and community in addressing
      barriers to learning. Current approaches are critiqued, and new directions for
      policy and practice are outlined.

PMID- 9250343
TI  - Preschool antecedents of adolescent assaultive behavior: a longitudinal study.
AB  - A 16-year longitudinal study followed preschool maltreated and nonmal-treated
      children to identify their involvement in assaultive behavior as adolescents.
      Severity of physical discipline, negative quality of the mother's interaction
      with the child, and the experience of sexual abuse were related to adolescent
      assaultive behavior.

PMID- 9250344
TI  - Relation of parental affective illness to family, dyadic, and individual
      functioning: an observational study of family interaction.
AB  - Family, dyadic, and individual functioning were examined in 18 control families
      and 41 families with a history of maternal affective illness-including 26 in
      which husbands also had a history of psychiatric illness. Assessments of
      functioning, based on observed family interactions, indicated that families with
      a history of affective illness are more likely to have functional problems, and
      that problems may differ as a function of type of diagnosis and number of ill
      parents. Findings suggest that clinical program planning should take into account
      variability within groups, as well as individual competencies.

PMID- 9250345
TI  - Attachment representations of personality-disordered criminal offenders.
AB  - The relation between attachment representations and personality disorders was
      examined in a sample of 40 Dutch men held in a forensic psychiatric hospital for
      the commission of serious crimes. Secure attachment representations were
      virtually absent in the sample; separation from attachment figures in childhood
      was related to current insecure attachment as well as to personality disorders.
      Use of attachment theory in research and clinical work with criminals is
      discussed.

PMID- 9250346
TI  - Parental bereavement: spiritual connections with deceased children.
AB  - Of a sample of 43 bereaved parents of pediatric cancer patients, 38 reported
      experiencing feelings of continued connection with their deceased child. Analysis
      of the data revealed several consistent themes in the experiences and in their
      impact on the parental bereavement process. Implications for research and
      clinical practice are discussed.

PMID- 9250347
TI  - Hemophilia and AIDS in married men: functioning of family members. Hemophilia PAC
      Project.
AB  - Aspects of functioning in families of 137 hemophilic men who, in 50% of cases,
      were also HIV seropositive were examined in terms of psychological and physical
      functioning and economic pressure. Results indicated that HIV-seropositive
      status, but not severity of hemophilia, was associated with poorer psychological
      and physical functioning of the husband, a poorer mother-child relationship, less
      support from outside the family for both spouses, and greater economic pressure
      on the family.

PMID- 9250348
TI  - Attachment, self-concept, and academic motivation in high-school students.
AB  - The contributions of parent and teacher attachment and self-concept to academic
      motivation were examined in a sample of 150 high-school students in the 11th and
      12th grades. Findings indicated that parent attachment and attachment to a
      teacher were individually and collectively related to academic motivation, and
      that academic self-concept was a significant predictor of academic motivation.

PMID- 9250349
TI  - Trauma in children of Holocaust survivors: transgenerational effects.
AB  - The effect of parental Holocaust trauma on their children's Jewish identity and
      Holocaust-related ideation was investigated by comparing survivors' children with
      children of American Jews. Parental communication style as a possible mediating
      factor was also assessed. Children of survivors showed significantly more
      Holocaust ideation than did those of American Jews, but did not differ
      appreciably on measures of Jewish identity. Parental communication style was
      associated with ethnic identification, suggesting its mediating influence on the
      transgenerational effects of parental trauma.

PMID- 9250350
TI  - Report on the Fifth International Workshop on Chromosome 9 held at Eynsham,
      Oxfordshire, UK, September 4-6, 1996.
AB  - The Fifth International workshop on chromosome 9 comprised a gathering of 36
      scientists from seven countries and included a fairly even distribution of
      interests along chromosome 9 as well as a strong input from more global
      activities and from comparative mapping. At least eight groups had participated
      in the goal set at the previous workshop which was to improve the fine genetic
      mapping in different regions of chromosome 9 by meiotic breakpoint mapping in
      allocated regions and this has resulted in some greatly improved order
      information. Excellent computing facilities were available and all contributed
      maps were entered not only into SIGMA (and thence submitted to GDB) but also into
      a dedicated version of ACEDB which can be accessed on the Web in the form of one
      of 28 slices into which the chromosome has been arbitrarily divided. It was
      generally agreed that the amount of data is now overwhelming and that the
      integration and validation of all data is not only unrealistic in a short meeting
      but probably impossible until the whole chromosome has been sequenced and fully
      annotated. Sequence-ready contigs presented at the meeting totalled about 3 MB
      which is about one fiftieth of the estimated length. The single biggest barrier
      to integration of maps is the problem of non-standard nomenclature of loci. In
      the past 2 workshops efforts have been made to compare traditional 'consensus'
      maps made by human insight (still probably best for small specific regions) with
      those generated with some computer assistance (such as SIGMA) and those generated
      objectively by defined computer algorithms such as ldb. Since no single form of
      map or representation is entirely satisfactory for all purposes the maps
      reproduced in the published version of the report are confined to one of the
      genetic maps, in which Genethon and older markers have been incorporated, a Sigma
      map of the genes as symbols together with a listing of known 'disease' genes on
      chromosome 9, and a revised assessment of the mouse map together with a list of
      mouse loci predicted to be on human chromosome 9. One of the 28 ACEDB slices is
      also shown to illustrate strengths and weaknesses of this approach. Workshop
      files include not only all maps available at the time but also details of loci
      and details of the meiotic breakpoints in the CEPH families
      (http:/(/)www.gene.ucl.ac.uk/scw9db.shtml) .

PMID- 9250351
TI  - Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency in south
      east Sicily.
AB  - In order to explore the nature of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency in south-east Sicily, we have analysed the G6PD gene in 25 unrelated
      males with abnormal G6PD activity and/or electrophoretic mobility, by using the
      analysis of the appropriate PCR-amplified fragment of DNA and subsequent
      digestion by appropriate restriction-enzymes, looking for the presence of certain
      known G6PD mutations. We amplified the entire G6PD coding sequence into eight
      fragments, followed by single-strand conformation polymorphism (SSCP) analysis
      and sequencing of those individual fragments that were found to be abnormal by
      SSCP. Through these methods we found a total of twelve G6PD Mediterranean
      variants with the association of a silent mutation 1311 (also known as
      polymorphic site Bcl I), one G6PD Mediterranean without this association, four
      G6PD A-Val 68 and two G6PD Santamaria and five G6PD Chatham. In a subject with
      normal activity a mutation was found in exon 5, designated as G6PD Sao Borja.
      This is the first report on the molecular analysis of G6PD mutations in Sicily
      and we have obtained evidence for four distinct classes of variants.

PMID- 9250352
TI  - Mutations associated with Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome (SLS), a rare autosomal disorder characterized by
      ichthyosis, spastic neurological disorders and oligophrenia, is associated with
      deficiency of fatty aldehyde dehydrogenase encoded by a gene on chromosome
      17q11.2. Mutations of the gene (GDB symbol ALDH10) were recently identified in
      three SLS patients. Another aldehyde dehydrogenase isozyme. ALDH3, also has a
      high activity for fatty aldehyde oxidation, and is encoded by a gene in
      chromosome 17q11.2. Abnormality of the ALDH3 gene could also cause a similar
      syndrome. The examination of the ALDH3 locus of three additional SLS patients
      showed that two are heterozygous with C-->G at nt 985 (Pro-->Ala at protein
      position 329). However, the mutation was found to be common (frequency of the
      atypical allele is about 0.25) in normal subjects, and not related to SLS.
      Isoelectric focusing analysis indicated that ALDH3 is hardly expressed in normal
      as well as patients' fibroblast cells, while ALDH10 expressed in the normal cells
      is diminished in the three patients' cells. The level of ALDH10 mRNA is also low
      in the patients' cells. The examination of the ALDH10 locus revealed the
      existence of a 3 base deletion coupled with a 21 base insertion at intron 6/exon
      7 junction in one patient. This abnormality is the same as that found in the
      patient previously reported by other investigators. One patient is associated
      with a 2 base deletion at nt 1297 and consequent premature chain termination at
      protein position 434. Another patient is a compound heterozygote for the same 2
      base deletion at nt 1297 and a 5 base insertion at nt 1311 and premature chain
      termination at protein position 457. Unique characteristics of the SLS mutations
      are pointed out.

PMID- 9250353
TI  - Segregation analysis of ovarian cancer using diathesis to include other cancers.
AB  - Despite the recent cloning of BRCA1, BRCA2 and the mismatch repair genes, it will
      still be a long time before it is possible to specify any individual's risk for
      ovarian cancer based on her genotype. Most women concerned about their risk on
      the basis of one or two affected relatives do not belong to extensive ovarian
      cancer families. Risk calculations depend on a reliable genetic model for ovarian
      cancer derived, ideally, from the population from which an individual is drawn.
      We have carried out a segregation analysis using data collected from consecutive
      ovarian cancer patients in two different centres in the UK. Complex segregation
      analysis was carried out with the addition of diathesis as a separate parameter
      allowing other cancers, associated with ovarian cancer, to be taken into account.
      The use of diathesis in the derivation of this alternative model is described.
      Analysed under joint likelihood without diathesis, the gene frequency is 0.0028
      and penetrance to age 70 years is 50%. This is in agreement with other published
      models. Incorporating diathesis into the model under joint likelihood gives
      similar parameters for a single locus model but gives the best fit with a two
      locus model where both genes are rare.

PMID- 9250354
TI  - Linkage of multilocus components of variance to polymorphic markers.
AB  - Haseman & Elston (1972) introduced a sib pair method using classical regression
      analysis to detect linkage between a polymorphic marker locus and any
      quantitative trait locus. Most of the diseases mapped to date follow simple
      Mendelian, single locus transmission. But there are many familial diseases that
      do not follow simple Mendelian segregation, for example diabetes, several forms
      of cancer, etc. In this paper, we extend Haseman and Elston's sib pair method to
      two unlinked quantitative trait loci each linked to one of two unlinked
      polymorphic marker loci. For the two-locus epistatic model, we give a general
      formulation of the complete regression model and details of the regression
      coefficients in terms of variance components.

PMID- 9250355
TI  - Extension of the Haseman-Elston method to multiple alleles and multiple loci:
      theory and practice for candidate genes.
AB  - The Haseman & Elston (1972) sibling-pair regression method has been used to
      detect and estimate the variance contribution to observed values of a
      quantitative trait by allelic variation in specific candidate genes. The
      procedure was developed under a model with a single biallelic trait locus. This
      assumption does not hold for several known systems. In this paper we prove that
      for candidate gene analysis the Haseman-Elston procedure extends to the case of
      multiple trait loci, each possibly having more than two alleles. Simulation
      experiments comparing single-locus to two-locus models show that fitting the
      extended regression equations maintains nominal significance levels, but the
      power to detect linkage to trait variation is not improved by including
      additional loci. These results indicate that the original proposal is
      statistically robust to violations of the underlying genetic model. Practical
      issues associated with quantifying the relative variance contribution by
      individual loci are also discussed. Applications of the extended regression
      equations to lipoprotein(a) and high density lipoprotein cholesterol are given
      for illustration.

PMID- 9250356
TI  - A new variant of the cytochrome P450c17 (CYP17) gene mutation in three patients
      with 17 alpha-hydroxylase deficiency.
AB  - A new CYP17 gene abnormality was found in three Japanese patients with 17 alpha
      hydroxylase deficiency (170HD). These patients were children from consanguineous
      marriages, but from two apparently unrelated families: one patient with 46, XY
      karyotype, and two siblings with 46, XX and 46, XY karyotypes. They were all
      raised as girls and presented with amenorrhea, eunuchoid appearance and
      hypertension. Gene analysis revealed two base-pair (TG) deletion in exon 5
      (codons 300, 301) of the CYP17 gene. This deletion could be expected to alter the
      reading frame resulting in the lack of a haem-binding region (Cys 442) due to a
      premature stop codon at position 333. This small mutation may account for the
      patients' clinical manifestations of 170HD.

PMID- 9250358
TI  - Tubulin synthesis and assembly in differentiating neurons.
AB  - Neurons are highly polarized cells that extend long processes, the axons and
      dendrites, to form contacts with target cells. The formation and maintenance of
      this specialized morphology relies on the assembly of an organized microtubule
      array that is the predominant component of the neuronal cytoskeleton. During this
      process there is an evolution in the composition and dynamics of microtubules,
      resulting in stable microtubule bundles that provide structural support and
      function in intracellular transport along the axon. In this essay we provide an
      overview of the mechanisms regulating the synthesis and assembly of tubulin in
      differentiating neurons with particular attention to the roles of multiple
      tubulin isotypes, posttranslational modifications of tubulin, and microtubule
      associated proteins. We conclude that, ultimately, the developmental regulation
      of microtubules in neurons may require the coordinated expression and
      posttranslational modifications of tubulin and microtubule-associated proteins to
      provide biochemical forms that favour specific interactions, each combination
      conferring distinctive dynamic and functional properties.

PMID- 9250357
TI  - Influence of the adenovirus 5 E1A oncogene on chromatin remodelling.
AB  - In the eukaryotic nucleus, compaction of DNA into chromatin can limit the access
      of trans-acting factors, providing an additional level of regulation to processes
      such as transcription, replication, and repair. Recent studies have suggested
      that the protein products of the adenovirus 5 E1A oncogene can influence SWI-SNF
      and histone acetylase activities, two cellular processes that facilitate
      transcription in the context of chromatin. This review focuses on the unexpected
      effects of E1A on cellular processes that remodel chromatin in relation to its
      transcriptional and transforming activities.

PMID- 9250359
TI  - Mammalian retinal pigment epithelial cells in vitro respond to the neurokines
      ciliary neurotrophic factor and leukemia inhibitory factor.
AB  - We examined whether primary cultures of rat retinal pigment epithelial (RPE)
      cells and RPE cells of an immortalized rat cell line, BPEI-1, would be responsive
      to the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory
      factor (LIF), which are known to be potent trophic factors for neuronal cells.
      Primary RPE cell cultures were characterized by indirect immunofluorescence and
      exhibited positive immunoreactivity for RET-PE2, a monoclonal antibody that
      recognizes RPE cells, and for the intermediate filaments cytokeratin and
      vimentin. The survival of cultured RPE cells in serum-free defined medium in the
      presence of CNTF or LIF was investigated during a 0- to 5-day period. Both CNTF
      and LIF, at concentrations of 1-50 ng/mL (4-200 pM), markedly enhanced RPE cell
      survival. Bromodeoxyuridine labelling of RPE cells revealed an increased mitotic
      activity in cell cultures treated with either CNTF or LIF in comparison to
      untreated serum-free cultures. Increases in cell survival and proliferation after
      neurokine treatment were also observed with the BPEI-1 cell line. However, in
      comparison to the primary RPE cultures, LIF was more effective than CNTF in
      promoting survival of the cell line over a 5-day treatment period. These studies
      demonstrate that the neurokines CNTF and LIF are potent trophic factors for
      mammalian RPE cells in vitro and may serve as candidate therapeutic agents in
      degenerative conditions that affect the retina and RPE.

PMID- 9250361
TI  - Mitochondrial gene expression in rat heart and liver during growth and
      development.
AB  - The levels of mitochondrial enzyme activities involved in respiration and
      oxidative phosphorylation and of specific mitochondrial gene transcripts were
      examined in rat heart and liver tissues during early growth, development, and
      aging. Increases were shown in cardiac respiratory complex activities I, III, IV,
      and V and ATPase6 and CoxII transcript levels during the transition from neonate
      to young adult. This increased mitochondrial gene expression is not associated
      with a proportionate increase in mitochondrial number. In contrast, no
      significant changes in liver mitochondrial activities or transcripts were
      detected during this transition. Marked reductions in the activities of complexes
      I, III, IV, and V and in ATPase6 and COXII transcripts were demonstrated in older
      adult as compared with young adult cardiac tissue with no concomitant reduction
      in cardiac citrate synthase activity and content, and mtDNA copy number. No
      decline was noted in liver mitochondrial enzyme activity levels and transcripts
      of old adult rats. These findings suggest that cardiac mitochondrial gene
      expression is developmentally regulated at a pretranslational level. The pattern
      of increasing mitochondrial gene expression in the young adult and decreasing
      gene expression in the aging heart stands in clear contrast to liver
      mitochondrial gene expression or nuclear-encoded genes such as citrate synthase.

PMID- 9250360
TI  - Visualization of muscarinic cholinergic receptors on chick cardiomyocytes and
      their involvement in phosphatidylcholine hydrolysis.
AB  - The purpose of this study was to visualize muscarinic receptors and their
      distribution on cardiomyocytes and to examine the effects of muscarinic
      cholinergic receptor (mACh-R) stimulation with carbachol on phosphatidylcholine
      hydrolysis. Cardiomyocytes were prepared as primary culture from 7-day-old chick
      embryo hearts. Cardiomyocytes, grown on cover slips, were labelled with BODIPY
      PZ, a fluorescent analog of the muscarinic receptor antagonist pirenzepine, and
      examined with a laser scanning confocal microscope, mACh-R clusters were
      visualized and were fairly homogeneous in size with diameters ranging from 0.5 to
      1.0 micron. The number of receptor clusters per cell was 83.5 +/- 6.8 (mean +/-
      SEM) and clusters were found at the periphery of the cell. Cardiomyocytes, grown
      as a monolayer in dishes, were treated with the 10(-4) M carbachol, a mACh-R
      agonist, and the effects on phosphatidylcholine hydrolysis were ascertained in
      cells preincubated with [methyl-3H]choline for 18 h. Cells were washed, lysed,
      and subjected to thin-layer chromatography to separate [3H]choline in various
      metabolites of phosphatidylcholine. Carbachol significantly (p < 0.05) increased
      intracellular free choline and decreased cellular phospholipid consistent with
      phosphatidylcholine hydrolysis. Carbachol increased the amount of [3H]choline
      that effluxed out of the cardiomyocyte into the medium. Carbachol-induced choline
      efflux was not prevented by pretreatment with n-butanol, a phospholipase D
      inhibitor, suggesting that other lipases such as phospholipase C are the major
      enzyme involved in phosphatidylcholine hydrolysis. Pertussis toxin prevented
      carbachol-induced choline efflux and the changes in intracellular free choline
      and phospholipid. An action of carbachol through G proteins was supported by the
      ability of pertussis toxin to antagonize the carbachol-induced reduction in cAMP
      generation from isoproterenol. In summary, mACh-Rs, visualized in living
      cardiomyocytes, were peripheral to the nucleus. Phosphatidylcholine hydrolysis
      induced by mACh-R stimulation may be a signal transduction pathway for mACh-R in
      the cardiomyocyte, operating through inhibitory G proteins sensitive to pertussis
      toxin.

PMID- 9250362
TI  - A consensus sequence for a functional human endogenous retrovirus K (HERV-K)
      dUTPase.
AB  - Amino acid sequence comparisons have revealed that a potential dUTPase gene is
      encoded by the retrovirus HERV-K, a defective multicopy virus that is transmitted
      vertically in humans. This gene is distinct from the human cellular dUTPase gene
      and thus two potential sources of the enzyme exist in human cells. dUTPases
      characterized from various sources each contain five conserved amino acid
      sequence motifs that form the active site of the enzyme. The protein sequence of
      the putative HERV-K dUTPase deduced from previous DNA sequence data from one
      proviral clone (HERV-K10) shows marked deviations at highly conserved residues in
      four of five of these motifs. Therefore, the reported DNA sequence may represent
      a mutated form of the viral dUTPase gene. To address this possibility, we cloned
      and sequenced 22 copies of the HERV-K dUTPase gene from human DNA. The results of
      this analysis indicate that variations evident in the HERV-K10 dUTPase amino acid
      sequence represent mutations of the wild-type viral DNA sequence. A version of
      the HERV-K dUTPase gene that corresponds to the ancestral, wild-type DNA sequence
      was constructed and adapted for expression in Escherichia coli. The resulting
      enzyme was found to exhibit properties similar to those of dUTPases isolated from
      other systems. A possible role of the HERV-K dUTPase in human disease is
      discussed.

PMID- 9250364
TI  - NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
AB  - The proton and carbon-13 NMR resonances for the 13-residue synthetic RRsrc
      peptide were completely assigned using two-dimensional NMR spectroscopy. This
      peptide contains a tyrosine in position 9 that can be phosphorylated by many
      tyrosine protein kinases. On the basis of observed nuclear Overhauser
      enhancements and alpha-proton and alpha-carbon chemical shifts, the peptide
      appears to interconvert between extended and nascent helical structures. The
      helical conformation found in aqueous solution is compared with the corresponding
      structure calculated for the tyrosine 416 site of pp60src by homology modeling to
      the cAMP-dependent protein kinase (PKA) and also to the conformation modelled
      after the bound form of a PKA-inhibitor peptide.

PMID- 9250363
TI  - Phosphorylation site substrate specificity determinants for the Pim-1
      protooncogene-encoded protein kinase.
AB  - Pim-1 is an oncogene-encoded serine-threonine kinase that is expressed primarily
      in cells of the hematopoietic system and germ line. The full-length coding
      regions of both human and Xenopus laevis Pim-1 were expressed as recombinant
      bacterial fusion proteins that autophosphorylated in vitro and exhibited
      phosphotransferase activity towards various exogenous substrates. The consensus
      sequence for phosphorylation by Pim-1 was defined by stepwise replacement of the
      amino acids in peptide substrate analogues based on the carboxyl-terminal segment
      of human ribosomal protein S6 (residues 229-249). The optimal substrate peptide
      for Pim-1 was determined to be Lys/Arg-Lys/Arg-Arg-Lys/Arg-Leu-Ser/Thr-X, where X
      is an amino acid residue with a small side chain. These results were confirmed
      using X. laevis Pim-1 expressed in COS cells. These findings could permit the
      identification of physiological substrates of Pim-1 and predict the location of
      phosphorylation sites within these proteins.

PMID- 9250365
TI  - The alpha-galactosyl specific lectin from Artocarpus integrifolia distinguishes
      between two lymphoma lines with different metastatic potential.
AB  - A lectin purified from the seeds of the Vietnamese Artocarpus integrifolia
      distinguishes between the mouse T-cell lymphoma cell lines Eb and ESb, with low
      and high metastatic potential, respectively. It agglutinates Eb cells as well as
      human erythrocytes, but not ESb cells or the human colon carcinomas cells HT29.
      The haemagglutinin is specific for alpha-galactosyl residues and has a molecular
      mass of 62 kDa.

PMID- 9250366
TI  - Hamster ribosomal protein S24 multigene family: genomic organization and
      molecular structure of two pseudogenes.
AB  - A cDNA coding for the hamster S24 ribosomal protein was used to isolate
      homologous genes from a Syrian hamster fibroblast genomic library. Southern
      analysis, using S24 ribosomal protein cDNA and two probes derived from the 5' and
      3' ends, suggests that the S24 ribosomal protein family is composed of at least 3
      related members in the hamster genome, and of 6-10 members in the mouse genome. I
      describe the isolation of nine independent lambda recombinant phages that
      altogether carry two different genes encoding S24 ribosomal proteins. Sequence
      analysis indicates that each of these two genes contain sequences related to the
      S24 ribosomal protein but lack introns and differ in their flanking sequences. On
      the basis of these features, I propose that these two genes are processed
      pseudogenes. Interestingly, one of them is flanked by two different repetitive
      sequences, homologous to satellite DNA, whose functions are unknown. I also show
      that in the hamster genome the S24 ribosomal protein mRNA is transcribed from a
      unique gene using a precise initiation site.

PMID- 9250367
TI  - Nutrient uptake into undifferentiated and differentiated HT-29 cells in culture.
AB  - HT-29 human colon carcinoma cells in culture have many characteristics of
      enterocytes, and these cells have been used by others to study intestinal drug
      and nutrient transport and metabolism. When grown in glucose-containing medium,
      HT-29 cells are largely undifferentiated (HT-29glu), but when grown in the
      absence of glucose but in the presence of galactose (HT-29gal), the population of
      cells is mostly differentiated. This study was undertaken with HT-29glu and HT
      29gal cells to study the uptake of palmitic acid (16:0), linoleic acid (18:2),
      and cholesterol. The relationship between concentration and uptake of 16:0, 18:2,
      and cholesterol was linear in HT-29glu and HT-29gal cells, with the relative
      values of the slopes of this relationship being 18:2 > > 16:0 > > cholesterol.
      The rates of uptake of these lipids were at least three times higher in HT-29gal
      than in HT-29glu cells. In HT-29glu cells, the relative rates of uptake of the
      sugars at 32 mM were D-glucose = galactose > fructose > > alpha-methylglucose.
      Uptake of these sugars was much greater in HT-29gal than in HT-29glu cells. When
      100 microM forskolin was added to the incubation medium for 7 days post
      confluency, which stimulates the activity of adenylate cyclase and thereby
      increases the intracellular synthesis of cAMP, there was no effect on the uptake
      of the lipids or the sugars in either HT-29glu or HT-29gal cells. Thus, (i)
      differentiated HT-29gal cells transport larger amounts of lipids and sugars than
      do undifferentiated HT-29glu cells; (ii) forskolin has no effect on the uptake of
      lipids or sugars in these cells. This human cell culture system may be useful to
      study the in vitro transport of lipids, to establish the role of cell
      differentiation on these uptake processes, and to determine the potential role of
      selected intracellular signals.

PMID- 9250368
TI  - 5-Hydroxytryptamine-induced endothelium-dependent and -independent relaxations in
      isolated dog anterior spinal small arteries.
AB  - The mode of action of 5-hydroxytryptamine (5HT) was investigated in isolated dog
      anterior spinal small arteries. Lower concentrations of 5HT (10(-9)-10(-7) M)
      caused a dose-dependent contraction and higher concentrations (10(-6)-10(-3) M)
      produced a dose-dependent relaxation of the arteries precontracted by 10(-7) M U
      46619. The 5HT-induced relaxation was significantly antagonized by methiothepin
      (10(-9)-10(-6) M). Ketanserin (10(-6) M) and ICS 205-930 (3 x 10(-6) M) did not
      affect the 5HT-induced relaxation of the arteries. The relaxant response to 5HT
      was reduced significantly by mechanical rubbing of the endothelial cells. The 5HT
      induced endothelium-independent relaxation was also antagonized significantly by
      methiothepin (10(-6) M). Aspirin (5 x 10(-5) M) or N omega-nitro-L-arginine
      methyl ester (L-NAME) (10(-6) M) significantly suppressed the 5HT-induced
      endothelium-dependent relaxation. L-Arginine (10(-3) M) also significantly
      reversed the L-NAME induced reduction of the 5HT-induced endothelium-dependent
      relaxation. Treatment with L-NAME in the presence of aspirin also produced much
      greater reduction of the 5HT-induced endothelium-dependent relaxation.
      Isocarbacyclin (10(-9)-10(-5) M) induced a concentration-dependent relaxation of
      the isolated spinal small arteries precontracted by 10(-7) M U 46619. These
      results suggest that 5HT induces endothelium-dependent and -independent
      relaxations of the isolated anterior spinal small arteries mainly via activation
      of 5HT1-like receptor and that endogenous nitric oxide and vasodilative
      prostaglandins may contribute to the 5HT-induced endothelium-dependent relaxation
      of the arteries.

PMID- 9250369
TI  - Effects of lisinopril on intercellular resistance of guinea pig ventricular
      myocytes.
AB  - Previous reports have suggested that angiotensin converting enzyme (ACE)
      inhibitors are able to modulate intercellular resistance through an ACE
      independent action. Therefore, the aim of our study was to determine whether the
      ACE inhibitor lisinopril would modulate intercellular resistance of guinea pig
      ventricular myocytes. Junctional resistance was measured using the double patch
      clamp technique in eight cell pairs at baseline and during superfusion with 10(
      4) M lisinopril. In these cell pairs, mean junctional resistance (+/-SEM)
      measured at baseline (14.5 +/- 3.8 M omega) was unchanged (15.0 +/- 3.6 M omega;
      p > 0.05) during lisinopril even after a 25-min exposure to the drug (n = 3). As
      well, a 20-min exposure to 10(-6) M lisinopril from the intracellular milieu did
      not modify the junctional resistance. In conclusion, this study demonstrates that
      modulation of junctional resistance independent of drug-related ACE inhibition is
      not observed with lisinopril.

PMID- 9250370
TI  - 2-Deoxy-D-glucose-induced changes in membrane potential, input resistance, and
      excitatory postsynaptic potentials of CA1 hippocampal neurons.
AB  - Temporary block of glycolysis by 2-deoxy-D-glucose (2-DG) reversibly suppresses
      synaptic transmission in the CA1 region of hippocampal slices. Recovery of
      responses is followed by a sustained potentiation of field excitatory
      postsynaptic potentials (EPSPs) (2-DG-LTP). To investigate the mechanisms
      involved in this type of LTP, we studied the effects of 2-DG on membrane
      properties of CA1 neurons (in slices from Sprague-Dawley rats), recorded with
      sharp intracellular electrodes containing 3 M KCl, as well as patch electrodes,
      filled mainly with 150 mM KMeSO4 and Hepes. The predominant change produced by 15
      to 20-min applications of 2-DG (10 mM, replacing glucose) was hyperpolarization
      (-5.6 +/- 1.1 mV for 18 intracellular recordings and -7.2 +/- 0.80 mV for 17
      whole-cell recordings) accompanied by a fall in resistance (-33 +/- 2.5% for 14
      intracellular recordings and -11.6 +/- 7.1% for 15 whole-cell recordings).
      Virtually identical hyperpolarizations were recorded in the presence of 20 microM
      glyburide (-5.5 +/- 1.5 mV, n = 6), but they were abolished by adenosine
      antagonists 8-(p-sulfophenyl)theophylline (8-SPT) and 8-cyclopentyl-3,7-dihydro
      1,3-dipropyl-1H-purine-2,6-dione (DPCPX) (2.8 +/- 1.6 and 4.0 +/- 1.7 mV,
      respectively; n = 5 for both). It was concluded that the hyperpolarization is
      most likely caused by an increase in K+ conductance, activated by a 2-DG-induced
      rise in adenosine release. After such applications of 2-DG, a sustained
      potentiation of EPSPs (similar to the 2-DG-LTP of field EPSPs) was evident in
      five neurons recorded with intracellular electrodes but not in any of nine whole
      cell recordings, where it was replaced by sustained, LTD-like depression. We
      conclude that a factor essential for 2-DG-LTP induction is lost during whole-cell
      recording.

PMID- 9250371
TI  - Expression of functional beta-adrenoceptors and polyploidy development in
      cultured vascular smooth muscle cells from spontaneously hypertensive rats.
AB  - The main objective of this study was to investigate the role of beta-adrenoceptor
      activation in the development of polyploidy in these cells. Smooth muscle cells
      (SMCs) were cultured from 3- to 4-, 10- to 12-, and 28- to 30-week-old
      spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY).
      Functional expression of beta-adrenoceptors was examined by treatment of cultured
      SMCs with a nonselective beta-adrenoceptor agonist, isoproterenol, or an
      adenylate cyclase activator, forskolin, or a membrane-permeable analog of
      adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromo-cAMP, and the measurement of
      intracellular cAMP levels, using a radioimmunoassay. The effects of these
      treatments on polyploidy development were also studied by measuring the DNA
      content of SMCs, using scanning microdensitometry. Treatments with isoproterenol
      or forskolin increased intracellular cAMP levels in both strains of rats in all
      three age groups. Addition of the beta-adrenoceptor antagonist DL-propranolol
      inhibited the isoproterenol-stimulated response in SMCs from both SHR and WKY in
      all three age groups. The number of polyploid SMCs was significantly increased by
      treatments with isoproterenol, forskolin, or 8-bromo-cAMP in SMCs from 3- to 4
      week-old WKY and SHR, but in the 10- to 12-week age group, an increase was found
      only in SMCs from WKY. Such treatments had no effect on the incidence of
      polyploid SMCs in the 28- to 30-week groups. We conclude that (i) beta
      adrenoceptors expressed by the SMCs from WKY and SHR at all three ages are
      functional and are coupled via Gs proteins to the stimulation of adenylate
      cyclase, (ii) treatments that elevate intracellular cAMP levels (by activation of
      beta-adrenoceptors or of adenylate cyclase) lead to increased polyploid SMCs from
      WKY and SHR in the younger age group, confirming a role for the beta-adrenoceptor
      adenylate cyclase pathway in the development of polyploidy in cultured SMCs from
      both of these strains of rats, and (iii) the absence of these treatment effects
      in the induction of polyploid SMCs in older age groups suggests that in these
      cells, other factors or processes may be involved in regulating the development
      of polyploid SMCs.

PMID- 9250372
TI  - Influence of nitric oxide and vasoactive intestinal peptide on the spontaneous
      and triggered electrical and mechanical activities of the canine ileum.
AB  - Modulation of canine ileal pacemaker activity by nitric oxide (NO) or vasoactive
      intestinal peptide (VIP) was studied during recording of the intracellular
      electrical and mechanical activity from the entire muscularis externa and from an
      isolated circular muscle preparation both cut in the long axis of the circular
      muscle. In the whole-thickness preparation with cholinergic and adrenergic nerve
      function blocked, the inhibitory junction potentials (IJPs) recorded near the
      myenteric plexus (MyP) or deep muscular plexus (DMP) were abolished by omega
      conotoxin GVIA (omega-CTX, 10(-7) to 3 x 10(-7) M), tetrodotoxin (TTX, 1 microM),
      or the NO synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NNA at 50 microM).
      IJPs from electrical field stimulation triggered slow waves (TSWs); after TTX or
      omega-CTX, TSWs still occurred, advanced in time and increased in amplitude after
      TTX. Addition of L-NNA advanced the onset of the TSWs after omega-CTX. TTX, L
      NNA, or omega-CTX left the resting membrane potentials, the characteristics of
      spontaneous slow waves, or TSWs evoked by a long stimulating pulse unchanged. L
      NNA at 100 microM enhanced the amplitude but not the frequency of spontaneous
      slow waves. TTX and NOS blockers all increased circular muscle contractions
      associated with the spontaneous slow waves and TSWs. In isolated circular muscle
      preparations, the NOS inhibitors N omega-nitro-L-arginine methyl ester (L-NAME at
      300 microM) or L-NNA at 100 microM abolished the IJPs and increased the
      regularity and amplitude of spontaneous slow waves and associated contractions,
      but TSWs could not be evoked before or after NOS inhibition. The NO donor 3
      morpholinosydnonimine hydrochloride (SIN-1) at 200 microM caused
      hyperpolarizations (10-15 mV) similar to the IJP mediator, attenuated the IJPs,
      and abolished mechanical activities. SIN-1 increased the slow wave frequency but
      decreased the amplitude and duration of spontaneous slow waves and TSWs. VIP (10(
      6) M) decreased contraction and slow wave amplitude and prolonged IJP duration
      without affecting membrane potential or slow wave frequency. We conclude that
      spontaneous slow waves and TSWs originate independently of neural activity.
      Pacemaking regions possess inhibitory neural inputs that release NO to mediate
      IJPs and relaxation and influence the delay before a TSW. NO (not VIP) release
      from nerves inhibits initiation of spontaneous slow waves or TSWs near the MyP,
      and spontaneous NO release modulates pacemaking activity from the DMP.

PMID- 9250373
TI  - Inhibition of the action of nitric oxide prodrugs by pyocyanin: mechanistic
      studies.
AB  - Previously, we reported on the antagonism by pyocyanin (PYO) of the relaxant
      effects of nitrovasodilators such as glyceryl trinitrate, S-nitroso-N
      acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1). The purpose of
      the present study was to elucidate the mechanism of this action of PYO by
      examining its effect on the steps considered to be necessary for nitrovasodilator
      induced relaxation of blood vessels. PYO (10 microM) attenuated the accumulation
      of guanosine-3',5'-cyclic monophosphate (cGMP) in rabbit aorta induced by
      nitrovasodilators SIN-1, SNAP, and GTN, 65, 81, and 67%, respectively.
      Additionally, PYO (1 or 10 microM) interfered with in vitro activation of soluble
      guanylyl cyclase. PYO did not inhibit vascular relaxation induced by 8-bromo
      cyclic guanosine monophosphate. PYO (10 microM) also decreased the quantity of
      nitric oxide measured in the headspace above intact vascular tissue incubated
      with glyceryl trinitrate in the presence of oxygen. These observations are
      consistent with the interpretation that PYO interfered with the nitrovasodilator
      action of glyceryl trinitrate by inactivation of NO or by inhibition of enzymatic
      biotransformation of GTN; this would result in decreased guanylyl cyclase
      activation and thus lowering cellular levels of cGMP. NO chemiluminescence
      studies with SIN-1 (10 microM) revealed that this NO donor produced NO in a time
      dependent manner and PYO (10 microM) caused no inhibition of NO production, but
      in fact, potentiated NO release after 10 min of incubation (1395 +/- 179 pmol NO
      compared with 1088 +/- 154 pmol NO). NO production from 10 microM SNAP was
      similarly potentiated by PYO after 0.5, 2, 5, and 10 min of incubation.
      Therefore, it is likely that PYO acts as an inhibitor of guanylyl cyclase with
      respect to NO donors, SIN-1 and SNAP, but it also appears that PYO can exert
      additional inhibitory effects in the case of vascular relaxation by GTN. Such
      differences in relaxant effects may reflect inhibition of enzymatic
      biotransformation that is unique to GTN or that PYO may complex with an
      alternative redox form of NO (perhaps NO+) that is generated by vascular
      metabolic activation of GTN.

PMID- 9250374
TI  - Submandibular glands: novel structures participating in thermoregulatory
      responses.
AB  - Since submandibular glands participate in the regulation of cardiovascular and
      immunological responses to bacterial endotoxin, we examined their role as
      modulators of endotoxin-induced fever. Core body temperatures were measured by
      telemetry in rats that had either a sham operation or a sialadenectomy 1 week
      previously and that were maintained at 23-24 degrees C. The sialadenectomized
      rats showed a circadian variation in body temperature similar to sham-operated
      rats, although their daytime body temperature was 0.24 +/- 0.01 degree C lower.
      The fever elicited by intraperitoneal injection of Escherichia coli endotoxin was
      biphasic, with an initial phase occurring between 2 and 3 h, and a broader second
      phase peaking between 4 and 8 h after endotoxin injection. The initial fever was
      similar in the two groups of rats, but the second phase of fever was
      significantly higher by 0.28 +/- 0.09 and 0.26 +/- 0.07 degree C in
      sialadenectomized rats receiving 50 or 150 micrograms/kg of endotoxin,
      respectively. Intravenous treatment with a novel peptide, submandibular gland
      peptide-T (SGP-T; 100 micrograms/kg), 30 min before endotoxin injection did not
      affect the early fever response, but significantly suppressed by 0.37 +/- 0.10
      degrees C the late-phase fever provoked by 150 micrograms/kg of endotoxin. These
      results suggest that the submandibular glands modulate thermogenic responses to
      inflammatory stimuli possibly through the endocrine release of hormones, such as
      SGP-T.

PMID- 9250375
TI  - The effect of nitric oxide and endothelin on skeletal muscle contractility
      changes when stimulation is altered.
AB  - To investigate the effect of endothelial-derived products on the force of
      contraction of blood-perfused skeletal muscle, we infused S-nitroso-N
      acetylpenicillamine (SNAP, 10(-4) M) (a nitric oxide (NO) donor), endothelin-1
      (ET-1, 10(-8) M), N-acetylpenicillamine (NAP, 10(-4) M), or saline at a constant
      vascular concentration into the vascular bed of pump-perfused dog gastrocnemius
      plantaris muscles in situ (n = 17). Muscles performed isometric twitch
      contractions at 0.5, 1.5, and 4 Hz and isometric tetanic contractions (150 ms, 50
      Hz) at 12 and 40 contractions/min. We perfused the muscle at a constant pressure
      at rest and for the first 3 min of the 6-min contraction period, and then
      switched to constant flow perfusion and infused the substance over the remaining
      3 min. Neither NAP nor saline had a significant effect on force of contraction or
      perfusion pressure. SNAP significantly attenuated developed force as compared
      with NAP at 40 contractions/min and at 1.5 and 4 Hz. The effect of SNAP on
      developed force was greater during twitch than tetanic contractions. ET-1 had no
      significant effect on twitch or tetanic developed force. To test for these
      results on another mammalian skeletal muscle preparation, we stimulated curarized
      trimmed mouse soleus in vitro for 500 ms at 50 Hz at either 2 or 4
      contractions/min in the presence of SNAP (10(-4) M) or ET-1 (10(-9) M). SNAP,
      which increased force at 1 contraction/90 s, had no significant effect at the
      higher contraction frequencies. The inhibition by ET-1 at 2 contractions/min
      disappeared at 4 contractions/min. Therefore the effect of both NO and ET-1 on
      mammalian skeletal muscle appears to be dependent upon contraction pattern and
      frequency.

PMID- 9250376
TI  - Decompensation of hepatic and cerebral acyl-CoA metabolism in BALB/cByJ mice by
      chronic riboflavin deficiency: restoration by acetyl-L-carnitine.
AB  - BALB/cByJ mice have an autosomal recessive deficiency of short-chain acyl-CoA
      dehydrogenase (SCAD) and show elevated excretion of urinary butyrylglycine,
      ethylmalonate, and methylsuccinate, which resembles the SCAD deficiency disorder
      in children. These mice are clinically normal, perhaps because of an efficient
      acyl-CoA conjugation system. We attempted to decompensate the acyl-CoA metabolism
      in mutant mice by chronic treatment with a riboflavin-deficient diet for 3 weeks
      to potentiate the SCAD deficiency. We studied the urinary profiles of organic
      acids, acylglycines, hepatic and cerebral profiles of carnitines, and ammonia to
      assess the potentiation of this disorder. Cerebral activity of choline
      acetyltransferase (ChAT) was determined to study the effects of acyl-CoA
      accumulation on the cholinergic system. The results indicate that in riboflavin
      deficient mutant mice, the excretion of ethylmalonate, methylsuccinate,
      butyrylglycine, and dicarboxylic acids was enhanced. Hepatic and cerebral free
      and esterified carnitines were reduced, indicating a potentiation of the
      secondary carnitine deficiency. Hepatic ammonia levels, but not cerebral ammonia
      or glutamine levels, were elevated, indicating a tendency towards secondary
      hyperammonemia. Brain choline acetyltransferase activity was significantly
      reduced in striatum, implying a reduced availability of cerebral acetyl-CoA or a
      decreased cerebral transport of choline: Most of these changes were partially or
      completely restored by a concomitant treatment with acetyl-L-carnitine (ALCAR).
      In summary, we conclude that BALB/cByJ mice with SCAD deficiency, but with a
      functional urea cycle, might have an adequate adaptive mechanism to adjust to an
      excessive acyl-CoA load without hyperammonemia at the cerebral level. However,
      any deficiency of vitamins or cofactors in the diet could disturb an adaptation
      to this disorder and produce an effect on the cholinergic system.

PMID- 9250377
TI  - Active 22Na+ transport by the intact lung during early postnatal life.
AB  - The lung relies upon epithelial active transport of Na+ to aid in the clearance
      of fluid from its air spaces. Because it is unknown whether the rate of active
      Na+ transport by the distal lung epithelium varies during early postnatal age, we
      performed studies in young guinea pigs (7 and 30 days after birth). We used a
      single pass isolated perfused lung model in which a Krebs Ringer bicarbonate
      solution containing 22Na+, [14C]sucrose, and FITC-dextran was placed into the air
      spaces of the lungs, and apparent permeability-surface area (PS) products were
      calculated after determining the changes in lung weight and the concentrations of
      the isotopes in the vascular effluent. The PS product for 22Na+, but not
      [14C]sucrose, decreased significantly at both ages when amiloride was infused
      (final concentration of 10(-4) M). Amiloride also decreased the rate of fluid
      clearance, as assessed by changes in organ weight, at both ages. Although the
      absolute rate of amiloride-sensitive 22Na+ transport increased with age,
      morphometric measurement of the alveolar region demonstrated that the rate of
      amiloride-sensitive 22Na+ transport per unit alveolar surface area was similar.
      These data indicate that although the guinea pig lung undergoes significant
      growth shortly after birth, the rate of amiloride-sensitive active Na+ transport
      per unit surface area remains constant. Since a component of weight loss was
      insensitive to amiloride, these in vivo studies suggest that the amiloride
      insensitive Na+ transport pathways previously identified in cultured lung
      epithelium exist in the intact lung.

PMID- 9250378
TI  - Role of GABA in cerebral cortex.

PMID- 9250379
TI  - Area and lamina-specific expression of GABAA receptor subunit mRNAs in monkey
      cerebral cortex.
AB  - Seven monkey-specific cDNAs corresponding to alpha 1, alpha 2, alpha 4, alpha 5,
      beta 1, beta 2, and gamma 2 GABAA receptor subunits were isolated and cloned;
      radioactive cDNA and cRNA probes were used for Northern blot analysis and in situ
      hybridization histochemistry of the primary visual, somatosensory, motor,
      temporal, and anterior parietal areas. alpha 1, beta 2, and gamma 2 subunit mRNAs
      were expressed at much higher levels than the other mRNAs, indicating that most
      cortical GABAA receptors are assembled from these three subunits. alpha 1, beta
      2, and gamma 2 were also more highly expressed in area 17 than in all other
      areas, reflecting the greater density of GABA cells and synapses in area 17. In
      all cortical areas, each subunit mRNA showed an individual pattern of laminar
      expression. alpha 1, beta 2, and gamma 2 subunit mRNAs were particularly high in
      layers II-III, IV, and VI, tending to follow patterns of receptor binding and
      immunocytochemical staining. The other transcripts had different patterns, which
      did not match binding or immunocytochemical localization patterns. alpha 5
      subunit mRNAs, which are highly expressed in development, were enriched in layer
      VI and the underlying white matter of visual cortex and in a layer IV-like strip
      in area 4, possibly reflecting the involvement of receptors formed from alpha 5
      polypeptides in trophic interactions in the cortical subplate and in the
      transient layer IV during development of these areas. Monocular deprivation for 1
      3 weeks, induced by intravitreal injection of tetrodotoxin, resulted in
      substantial reductions in levels of alpha 1, beta 2, and gamma 2 subunit mRNAs in
      deprived ocular dominance columns of the visual cortex, but the other subunit
      mRNAs were largely unaffected by monocular deprivation. In cortical layers in
      which expression of any of the transcripts was high, all neurons appeared to
      express the gene, but in layers in which expression was low or moderate,
      differences in the degree of labeling of individual neurons suggested that some
      neurons may not express certain subunit transcripts in detectable amounts.
      Laminar differences in expression of different GABAA receptor subunits in
      cerebral cortex suggest the assembly of functional receptors from different
      arrangements of available subunits in different types of cell. Receptors with
      different functional properties may be assembled from different combinations of
      subunit polypeptides in different layers and in the visual cortex may be
      differentially regulated under activity-dependent conditions.

PMID- 9250380
TI  - Development and plasticity of the inhibitory neocortical circuitry with an
      emphasis on the rodent barrel field cortex: a review.
AB  - The present paper reviews current knowledge of the development and plasticity of
      the inhibitory gamma-aminobutyric acid (GABA) containing circuitry of the
      cerebral neocortex, in particular, the rat somatosensory barrel field cortex.
      Recent studies reveal a delayed and protracted maturation of the inhibitory
      compared with the excitatory cortical system, both at the neuronal and synaptic
      levels. This characteristic developmental pattern leaves a longer time window
      during which behaviourally relevant activity coming from the periphery can
      influence the organization of the GABA system. Indeed, sensory deprivation
      experiments confirm the involvement of the GABA system in phenomena of experience
      dependent cortical plasticity. Changing the pattern and level of afferent
      activity of in the rat somatosensory system during development by removing
      vibrissae results in a significant decrease in the number of GABA neurons and
      synapses in the thalamocortical recipient layer IV. Particularly affected are
      GABA synapses contacting dendritic spines, the number of which decreases by
      almost two-thirds. The involvement of the GABA system in events of experience
      dependent plasticity contributes to the adequate functioning of the cerebral
      cortex in the conditions of constantly changing environment and varying
      individual experience.

PMID- 9250382
TI  - Synaptic plasticity in hippocampal interneurons? A commentary.
AB  - The hypothesis that excitatory synapses onto hippocampal inhibitory interneurons
      undergo forms of synaptic plasticity similar to that observed in principal
      pyramidal neurons has received much attention in the last few years. No general
      consensus exists, however, concerning the presence (or absence) of long-term
      potentiation and depression in nonpyramidal neurons. A large source of this
      disagreement stems from the experimental paridigms chosen to elicit synaptic
      plasticity in the various studies, since most of the induction protocols used did
      not permit the separation of plasticity occurring on principal cells from
      possible direct plasticity on the interneurons themselves. In this commentary we
      discuss some of the issues surrounding these data and also address some of the
      technical considerations one must address before the presence or absence of long
      term potentiation in interneurons can be answered unequivocally.

PMID- 9250381
TI  - Inhibitory control of GABAergic interneurons in the hippocampus.
AB  - Hippocampal GABAergic interneurons are responsible for controlling the output and
      efficacy of synaptic input of large principal cell populations and, thereby,
      determine the oscillatory discharge patterns and synaptic plasticity in the
      hippocampus. Single interneurons are able to prevent repetitive firing of
      postsynaptic pyramidal cells (R. Miles, K. Toth, A.I. Gulyas, N. Hajos, and T.F.
      Freund. Neuron, 16: 815-823, 1996), whereas on occasion a single pyramidal cell
      may be able to activate an interneuron under in vitro conditions (A.I. Gulyas, R.
      Miles, A. Sik, K. Toth, N. Tamamaki, and T.F. Freund. Nature (London), 366: 683
      687, 1993). Inhibition is therefore extremely powerful. Transient suppression of
      interneuronal activity allows the precise timing and synchronization of
      inhibitory postsynaptic potentials arriving at principal cells. A rhythmic
      suppression or modulation of interneuron discharge may be brought about by input
      from at least two major sources: (i) from other local interneurons or (ii) from
      subcortical centers. Of the possible local sources, in the present review
      particular attention will be paid to GABAergic neurons specialized to innervate
      other interneurons. Subcortical pathways known to modulate specific inhibitory
      functions in the hippocampus, i.e., the GABAergic and cholinergic
      septohippocampal and the serotonergic raphe hippocampal pathways, will also be
      reviewed. Roles of these control mechanisms may include the generation of theta
      and higher frequency oscillations and the selective removal of inhibition from
      the termination zone of specific excitatory afferents, thereby increasing their
      efficacy and (or) plasticity.

PMID- 9250383
TI  - Properties of spontaneous miniature GABAA receptor mediated synaptic currents in
      area CA3 of rat hippocampal slice cultures.
AB  - Miniature, gamma-aminobutyric acid A receptor mediated inhibitory postsynaptic
      currents (mIPSCs) were recorded from CA3 pyramidal cells in hippocampal slice
      cultures using whole-cell techniques in the presence of tetrodotoxin. The
      kinetics and amplitudes of the mIPSCs were analyzed with the aim of determining
      whether subclasses of events arising from distinct populations of presynaptic
      interneurons could be distinguished. Histograms of mIPSC amplitude, rise time
      constant, and decay time constant were all positively skewed, but discrete
      subsets of events could not be distinguished. The positive skew did not appear to
      result from electrotonic filtering of distal synaptic currents because there was
      no correlation among mIPSC amplitudes and the kinetic parameters. Analysis of the
      intervals between mIPSCs indicated that each event occurred independently. The
      analysis of spontaneous mIPSCs does not provide evidence of the innervation of
      pyramidal cells by heterogeneous interneurons.

PMID- 9250384
TI  - Chronic focal neocortical epileptogenesis: does disinhibition play a role?
AB  - Several lines of evidence have suggested that decreases in postsynaptic
      inhibition may have a role in epileptogenesis in cortical structures. However,
      other studies have suggested that GABAergic inhibition is spared, or even
      augmented in some forms of post-lesional epilepsy. In the studies described here,
      inhibitory events were recorded in two models of post-lesional chronic
      epileptogenesis. (i) As previously reported (D.A. Prince and G.-F. Tseng. J.
      Neurophysiol. 69: 1276-1291. 1993), epileptiform activity develops in slices from
      partially isolated rat neocortical islands 2-3 weeks after the initial in vivo
      lesion. In this model of post-traumatic epilepsy, large amplitude polyphasic
      inhibitory postsynaptic currents (IPSCs) in layer V pyramidal neurons are
      associated with each interictal epileptiform field potential. The frequency of
      spontaneous IPSCs as well as miniature IPSCs was significantly increased in
      neocortical slices from the epileptogenic chronically injured cortex versus
      controls. Immunocytochemical reactions for parvalbumin and calbindin, calcium
      binding proteins present in subgroups of GABAergic neurons, showed an increased
      staining of both neuropil and somata within the epileptogenic tissue.
      Immunoreactivity for glutamic acid decarboxylase (GAD) and GABA also appeared to
      be increased in the neuropil. (ii) Cortical microgyri resembling human
      malformations were produced by freeze lesions made transcranially in P0 rat
      cortex (K.M. Jacobs, M.J. Gutnick, and D.A. Prince. Cereb. Cortex, 6: 514-523.
      1996). The boundary between the four-layered microgyrus and surrounding cortex
      become epileptogenic within about 2 weeks, as judged by evoked extracellular
      field potentials and cellular activities. Epileptogenesis in the surrounding
      cortex is not altered when the microgyrus itself is isolated by transcortical
      cuts. Patch-clamp recordings from layer V neurons in the epileptogenic zone
      showed that spontaneous IPSCs are larger and more dependent on glutamatergic
      synapses than in control neurons. The amplitudes of polysynaptic IPSCs evoked by
      threshold stimulation were also larger than in control cells. Although evaluation
      of inhibitory events in these models is still incomplete, results to date suggest
      that GABAergic inhibition may be enhanced in epileptogenic areas associated with
      chronic cortical injury. Sprouting of axonal arborizations of pyramidal cells
      onto interneurons, upregulation of GABAergic neurons, and perhaps sprouting of
      inhibitory axons that make increased numbers of contacts onto pyramidal cells may
      all contribute to the increased inhibitory drive. Results in these models do not
      support the disinhibitory hypothesis of chronic epileptogenesis.

PMID- 9250385
TI  - Functions for interneuronal nets in the hippocampus.
AB  - Recent advances in the physiology of hippocampal interneurons are summarized in
      this article. These findings suggest that through their interconnectivity
      inhibitory interneurons can maintain large-scale oscillations at various
      frequency ranges (theta, gamma, and 200-Hz bands). We suggest that networks of
      inhibitory interneurons within the forebrain impose coordinated oscillatory
      "contexts" for the "content" carried by networks of principal cells. These
      oscillating inhibitory networks may provide the precise temporal structure
      necessary for ensembles of neurons to perform specific functions, such as memory
      trace formation and retrieval. In addition, synaptic inhibition is shown to
      reduce the somadendritic backpropagation of sodium spikes and to prevent the
      occurrence of calcium spikes in dendrites. These observations indicate that
      interneurons are in an excellent position to control neuronal plasticity and
      allow synaptic transmission either with or without long-term modification of
      synaptic strength.

PMID- 9250386
TI  - The depolarizing GABA response.
AB  - In some situations the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)
      elicits a hyperpolarizing response (H response) followed by a depolarizing
      response (D response) on cortical neurons. It has recently been established that
      the D response on hippocampal pyramidal cells is largely carried by bicarbonate
      ions (HCO3-). However, there is still controversy over whether the
      hyperpolarizing and depolarizing responses to GABA are mediated by the same
      receptor channel. A relatively new single receptor channel model proposes that
      the D response appears because chloride (Cl-) accumulates as a results of the Cl(
      )-HCO3- conductance mediating the GABA response, dissipating the Cl- driving
      force and unmasking a net inward HCO3- current. This chloride accumulation model
      has gained favor because it provides an explanation for why higher concentrations
      of GABA are required to elicit the D response and why the D response generally
      follows an H response. On the other hand, there are some data that are best
      explained if there are two separate types of receptor channels mediating the H
      and D responses. This paper presents evidence for and against both the chloride
      accumulation hypothesis and the two different receptor channels hypothesis in the
      hope that investigators will recognize that this key problem concerning the
      generation of the D response remains unsolved.

PMID- 9250387
TI  - Do GABAA and GABAB inhibitory postsynaptic responses originate from distinct
      interneurons in the hippocampus?
AB  - GABAergic inhibition of hippocampal pyramidal cells is mediated by two distinct
      subtypes of postsynaptic receptors, GABAA and GABAB. Electrical stimulation of
      inhibitory cells or fibres in the CA1 subfield of the hippocampus yields a
      biphasic inhibitory postsynaptic potential (IPSP) in pyramidal cells, consisting
      of an early GABAA- and a late GABAB-mediated component. CA1 interneurons are a
      heterogeneous population of cells, which differ on the basis of their morphology,
      physiological properties, target selectivity onto principal cells, and network
      connectivity. Inhibitory synaptic circuitry appears to be specialized, since
      feedback inhibition may invoke only postsynaptic GABAA receptors, whereas
      feedforward inhibition may invoke both postsynaptic GABAA and GABAB receptors. In
      this review, we examine the evidence for and against the notion that distinct
      interneurons may be responsible for GABAA- and GABAB-mediated inhibition.
      Overall, the evidence suggests that (i) certain interneurons may generate solely
      GABAA inhibition, but the available data do not distinguish whether other
      interneurons mediate (ii) solely GABAB inhibition or (iii) a combination of both
      GABAA and GABAB.

PMID- 9250388
TI  - Functional and pharmacological properties of GABA-mediated inhibition in the
      human neocortex.
AB  - This paper describes some functional and pharmacological properties of GABA
      mediated mechanisms in the human neocortex maintained in vitro in a slice
      preparation. Neocortical neurons recorded intracellularly under normal conditions
      generate stimulus-induced and spontaneous potentials that are mediated by the
      activation of postsynaptic GABAA and GABAB receptor subtypes. As reported in
      other species, pharmacological blockade of the GABAA receptor makes epileptiform
      bursts appear in response to extracellular focal stimuli, thus indicating that
      inhibition mediated through the activation of the GABAA receptor exerts an
      important role in controlling neuronal excitability in the human neocortex.
      Spontaneous, prolonged epileptiform discharge are recorded when slices are bathed
      in Mg(2+)-free medium. Under these experimental conditions GABAA receptor
      mediated potentials occur between epileptiform events; moreover their rate of
      occurrence decreases shortly before the onset of each discharge. Blockade of
      GABAA receptor mediated potentials during application of Mg(2+)-free medium (i)
      prolongs the epileptiform discharges, (ii) increases the amplitude of their field
      potential DC shifts, and (iii) augments the concomitant decreases in [Ca2+]0 and
      increases in [K+]0. These findings indicate therefore that GABAA receptor
      mediated inhibitory potentials are operant during Mg(2+)-free epileptiform
      activity, and modulate the occurrence of epileptiform discharges. Moreover, they
      may also play a role in controlling the changes in [Ca2+]0 and [K+]0 that
      accompany each epileptiform event.

PMID- 9250389
TI  - Mechanisms controlling neuronal plasticity in somatosensory cortex.
AB  - gamma-Aminobutyric acid containing neurons in the somatosensory cortex are the
      major controlling element determining receptive field size and location. This
      control of the excitability of cortical neurons can be modulated by activity
      arising in the basal forebrain. A hypothesis is developed stating that both
      cholinergic and gamma-aminobutyric acid containing projections from the basal
      forebrain play important roles in the production of a state in cortex permitting
      neuronal plasticity to occur. This proposed mechanism involving a simultaneous
      reduction of inhibition and increased release of acetylcholine allows sensory
      signals to induce long-term changes in the location and responsiveness of
      cutaneous receptive fields, thereby changing the somatotopic organization of
      primary somatosensory cortex.

PMID- 9250390
TI  - Molecular chaperones and the heat shock response at Cold Spring Harbor.

PMID- 9250391
TI  - Hsp30, the integral plasma membrane heat shock protein of Saccharomyces
      cerevisiae, is a stress-inducible regulator of plasma membrane H(+)-ATPase.
AB  - Saccharomyces cerevisiae has a single integral plasma membrane heat shock protein
      (Hsp). This Hsp30 is induced by several stresses, including heat shock, ethanol
      exposure, severe osmostress, weak organic acid exposure and glucose limitation.
      Plasma membrane H(+)-ATPase activities of heat shocked and weak acid-adapted,
      hsp30 mutant and wild-type cells, revealed that Hsp30 induction leads to a
      downregulation of the stress-stimulation of this H(+)-ATPase. Plasma membrane
      H(+)-ATPase activity consumes a substantial fraction of the ATP generated by the
      cell, a usage that will be increased by the H(+)-ATPase stimulation occurring
      with several Hsp30-inducing stresses. Hsp30 might therefore provide an energy
      conservation role, limiting excessive ATP consumption by plasma membrane H(+)
      ATPase during prolonged stress exposure or glucose limitation. Consistent with
      the role of Hsp30 being energy conservation, Hsp30 null cultures give lower final
      biomass yields. They also have lower ATP levels, consistent with higher H(+)
      ATPase activity, at the glucose exhaustion stage of batch fermentations (diauxic
      lag), when Hsp30 is normally induced. Loss of Hsp30 does not affect several
      stress tolerances but it extends the time needed for cells to adapt to growth
      under several stressful conditions where the maintenance of homeostasis will
      demand an unusually high usage of energy, hsp30 is the first yeast gene
      identified as both weak organic acid-inducible and assisting the adaptation to
      growth in the presence of these acids.

PMID- 9250392
TI  - Metabolite changes associated with heat shocked avian fibroblast mitochondria.
AB  - A previous report from our laboratory (Collier et al 1993) showed that the
      elongated tubules of mitochondria in the cytoplasm of cultured chicken embryo
      fibroblasts collapsed to irregularly shaped structures surrounding the nuclear
      membrane after a 1 h heat shock treatment. The normal mitochondrial morphology
      reappeared upon removal of the thermal stress. We have now determined that
      several changes occurred in mitochondrial-related metabolites under these same
      heat shock and recovery conditions. Among these were significant decreases in the
      levels of fumarate and malate and increases in the amounts of aspartate and
      glutamate. In contrast, other intermediates of the tri-carboxylic acid cycle were
      unaltered as were levels of ATP and phosphocreatine. The changes observed might
      result from heat shock-induced changes in enzyme activities of the mitochondria,
      from alterations in the membrane-embedded specialized carrier proteins that
      transport metabolites between cytosol and mitochondria or from a disorganization
      of the electron-transport system normally coupled to oxidative metabolism. The
      rapid recovery, however, suggested that these changes were transient and readily
      reversible.

PMID- 9250393
TI  - The molecular response to reductive stress in LLC-PK1 renal epithelial cells:
      coordinate transcriptional regulation of gadd153 and grp78 genes by thiols.
AB  - Organic thiols are toxic to eukaryotic cells. Treatment of cells with thiols
      activates expression of grp78, but it is not known if, like other forms of
      stress, there is a battery of stress response genes that are induced by thiols.
      In LLC-PK1 renal epithelial cells, mRNAs for both grp78 and gadd153 were induced
      by thiols with similar time, concentration and structure-activity dependence.
      Dithiothreitol (DTT) was the most potent reductant and inducer of gene expression
      among the thiols tested. Nuclear run-on assays demonstrated that DTT activated
      both grp78 and gadd153 genes transcriptionally. A hamster gadd153 promoter
      construct which contains enhancer elements necessary for gadd153 activation was
      stably integrated into the LLC-PK1 cell genome and was activated by DTT. Although
      auto-oxidation of thiols can generate active oxygen species, transcriptional
      activation of the gadd153 promoter was not due to formation of hydrogen peroxide
      or superoxide since neither catalase nor superoxide dismutase prevented
      activation of the gadd153 promoter by DTT. The concentration dependence for
      activation of the gadd153 promoter correlated with inhibition of dome formation
      and protein synthesis, two toxic effects of DTT in LLC-PK1 cells. Thus, both
      grp78 and gadd153 are members of a gene battery which is responsive to reductive
      stress. There appears to be considerable, but not complete, overlap between the
      upstream signaling pathways for activation of both genes.

PMID- 9250394
TI  - The protein kinase inhibitor SB203580 uncouples PMA-induced differentiation of HL
      60 cells from phosphorylation of Hsp27.
AB  - HL-60 cells are an attractive model for studies of human myeloid cell
      differentiation. Among the well-examined parameters correlated to differentiation
      of HL-60 cells are the expression and phosphorylation of the small heat shock
      protein Hsp27. Here we demonstrate that PMA treatment of HL-60 cells stimulates
      different MAP kinase cascades, leading to significant activation of ERK2 and p38
      reactivating kinase (p38RK). Using the protein kinase inhibitor SB 203580, we
      specifically inhibited p38RK and, thereby, activation of its target MAP kinase
      activated protein kinase 2 (MAPKAP kinase 2), which is the major enzyme
      responsible for small Hsp phosphorylation. As a result, PMA-induced Hsp27
      phosphorylation is inhibited in SB 203580-treated HL-60 cells indicating that
      p38RK and MAPKAP kinase 2 are components of the PMA-induced signal transduction
      pathway leading to Hsp27 phosphorylation. We further demonstrate that, although
      PMA-induced phosphorylation is inhibited, SB 203580-treated HL-60 cells are still
      able to differentiate to the macrophage-like phenotype as judged by decrease in
      cell proliferation, induction of expression of the cell surface antigen CD11b and
      changes in cell morphology. These results indicate that, although correlated,
      Hsp27 phosphorylation is not required for HL-60 cell differentiation. However,
      the results do not exclude that increased Hsp27 expression is involved in HL-60
      cell differentiation.

PMID- 9250395
TI  - Hsp70 protects macrophages infected with Salmonella choleraesuis against TNF
      alpha-induced cell death.
AB  - Hsp70 plays an important role in cytoprotection against tumor necrosis factor
      (TNF) alpha-mediated cytotoxicity. To investigate the role of Hsp70 in
      cytoprotection during Salmonella infection, we examined endogenous Hsp70
      induction and TNF-alpha production in a monocyte/macrophage line, J774A.1, after
      infection with a virulent strain of Salm. choleraesuis RF-1 carrying a 50 kb
      virulent plasmid or the plasmid-cured avirulent strain 31N-1. Intracellular
      bacteria progressively increased in J774A.1 cells phagocytosing virulent RF-1
      bacteria, whereas such progressive growth was not evident in J774A.1 cells
      phagocytosing avirulent 31N-1 bacteria. On the contrary, J774A.1 cells infected
      with virulent RF-1 bacteria expressed less Hsp70 than those infected with
      avirulent 31N-1 bacteria. The level of TNF-alpha production by J774A.1 infected
      with virulent RF-1 was much the same as that by J774A.1 infected with avirulent
      31N-1. J774A.1 infected with virulent RF-1 died spontaneously; death was
      inhibited by the addition of anti-TNF-alpha mAb. Although the frequency of dead
      J774A.1 with hypodiploid DNA content increased only marginally after infection
      with avirulent 31N-1, treatment with Hsp70 anti-sense oligonucleotide resulted in
      a dramatic increase of dead cells in the infected macrophages. Taken together,
      these results suggest that Hsp70 induced in infected macrophages plays an
      important role in host defense against Salmonella infection by protecting the
      macrophages against TNF alpha-induced cell death. Furthermore, cell death due to
      impaired endogenous Hsp synthesis in the phagocytes implies a novel pathogenic
      mechanism for virulence of Salm. choleraesuis RF-1.

PMID- 9250396
TI  - Deleterious consequences of Hsp70 overexpression in Drosophila melanogaster
      larvae.
AB  - We compared transgenic Drosophila larvae varying in hsp70 copy number to assess
      the consequences of Hsp70 overexpression for growth and development after heat
      shock. Exposure to a mildly elevated temperature (36 degrees C) induced
      expression of Hsp70 (and presumably other heat shock proteins) and improved
      tolerance of more severe heat stress, 38.5-39.5 degrees C. We examined this
      pattern in two independently derived pairs of extra-copy and excision strains
      that differed primarily in hsp70 copy number (with 22 and 10 copies,
      respectively). Extra-copy larvae produced more Hsp70 in response to high
      temperature than did excision larvae, but surpassed the excision strain in
      survival only immediately after thermal stress. Excision larvae survived to
      adulthood at higher proportions than did extra-copy larvae and grew more rapidly
      after thermal stress. Furthermore, multiple pretreatment reduced survival of 1st
      instar extra-copy larvae, but did not affect the corresponding excision strain.
      While extra Hsp70 provides additional protection against the immediate damage
      from heat stress, abnormally high concentrations can decrease growth, development
      and survival to adulthood.

PMID- 9250397
TI  - Hsp70 expression and function during gametogenesis.
AB  - The dramatic transformations in nuclear content and cellular organization that
      occur during gametogenesis require unique regulation and execution of the mitotic
      and meiotic cell cycle, apoptotic cell death, DNA recombination and repair, and
      cellular differentiation. These processes are accompanied by the constitutive and
      developmentally regulated expression of a number of hsp70 genes encoding 70 kDa
      heat shock proteins (Hsp70), including several hsp70s whose expression is unique
      to male germ cells. Examining the expression and function of Hsp70s in germ cells
      has provided significant insights into mechanisms of hsp70 gene regulation and
      Hsp70 protein function, as well as the developmental processes of gametogenesis.

PMID- 9250398
TI  - Fit for life? Evolution of chaperones and folding catalysts parallels the
      development of complex organisms.

PMID- 9250399
TI  - Murine 86-kDa heat shock protein gene and promoter.
AB  - The class of 90 kDa heat shock proteins (Hsp90) is among the most abundant heat
      shock proteins (Hsps) in eukaryotic cells. In vertebrates, Hsp90 is encoded by
      two distinct gene families giving rise to products of 84 and 86 kDa. In mice the
      expression of these two genes, hsp84 and hsp86, vary with respect to each other
      in responses to stress, and also in response to signals for growth and
      development. Therefore, as a step towards understanding the molecular basis for
      the differential regulation of these two genes, we have isolated and
      characterized genomic clones of the murine hsp86 gene and its 5' flanking region.
      The gene is composed of eleven exons interrupted by 10 introns. The 5' region
      contains consensus TATA, several stimulatory protein-1 binding site (SP1)
      elements as well as six consensus heat shock elements (HSE) 5' of the
      transcription start site. An 806 bp fragment of the 5' promoter region conferred
      constitutive expression upon a reporter gene and this expression was increased
      upon heat shock.

PMID- 9250400
TI  - Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous
      endothelial cells in response to cytokines and oxidized low-density lipoproteins.
AB  - T-cells and monocytes are the first cells infiltrating the arterial intima during
      the early stages of atherogenesis. Recently our laboratory has provided evidence
      that T-cells isolated from atherosclerotic intima reacts against heat shock
      protein 60 (Hsp60). Transmigration of activated T-cells into the intima is
      mediated by adhesion molecules (ICAM-1; VCAM-1; ELAM-1) expressed on activated
      endothelial cells. Here we studied the potential of cytokines (TNF-alpha, IFN
      gamma, IL-1). Escherichia coli lipopolysaccharide (LPS), native and oxidized low
      density lipoprotein (LDL; oxLDL) and high temperature to induce adhesion
      molecules as well as Hsp60 and Hsp70 expression in human endothelial cells (EC).
      On Northern blots, a strong signal for ICAM-1, VCAM-1 and ELAM-1 was detected
      after 4 h, which thereafter declined, but did not reach the basal level of
      untreated control cells. Heat shock induced the expression of Hsp60 and Hsp70 but
      not of adhesion molecules. EC were cultivated in serum-free medium, which led to
      the expression of adhesion molecule transcripts. Addition of LDL or oxLDL to
      these ECs did not alter the expression of these transcripts. The production of
      adhesion molecule proteins was analysed by flow cytometry. In human venous
      endothelial cells (HVEC) and human arterial endothelial cells (HAEC) ICAM-1 and
      VCAM-1 production was permanently highly induced, whereas the high level of ELAM
      1 production at 4 h disappeared after 24 h. Furthermore, only HAEC, but not HVEC,
      produced ICAM-1, VCAM-1 and ELAM-1 after stress by moderately and highly oxLDL.
      LDL and oxLDL did not induce the production of Hsp60 and Hsp70. The present study
      demonstrates the co-expression of Hsp60 and adhesion molecules in arterial and
      venous EC in response to cytokine and LPS exposure, and that oxLDL is an
      efficient inducer of adhesion molecules in arterial EC and not in venous EC.
      These features provide the prerequisites for a cellular immune reaction against
      Hsp60 expressed by stressed EC in the initial stages of atherosclerosis.

PMID- 9250401
TI  - Potentiation of heat stress-induced hsp70 expression in vivo by aspirin.
AB  - Studies in cultured cells have demonstrated that non-steroidal anti-inflammatory
      agents can potentiate heat-induced hsp70 expression through activation of HSF1 to
      a DNA binding state. We investigated the influence of aspirin on hsp70 expression
      in intact rats subjected to heat stress. Rats were injected intraperitoneally
      either with aspirin (100 mg/kg) or vehicle alone, 60 min prior to their placement
      at 37 degrees C or room temperature for 30 min. hsp70 mRNA expression was
      analyzed in lung, liver and kidney isolated from animals assigned to one of four
      different treatment paradigms; untreated controls, heat, aspirin, and aspirin
      plus-heat. Comparison of hsp70 expression in the treatment groups revealed that
      in all tissues examined, aspirin-plus-heat treatment resulted in 3-4 fold higher
      levels of hsp70 mRNA relative to those seen with heat treatment alone. Little or
      no hsp70 mRNA expression was detected in the unheated groups, regardless of
      aspirin treatment. In keeping with the mRNA expression, Hsp70 protein levels were
      also elevated in aspirin-plus-heat treated animals. Aspirin treatment did not
      alter hsp70 protein expression in the absence of heat. In contrast to in vitro
      observations, aspirin treatment in vivo did not alter HSF1 DNA binding
      properties. Core body temperature measurements revealed that aspirin pretreatment
      enhanced the rise in body temperature seen in response to heat treatment. This
      increased hyperthermic response to heat stress probably accounts for the
      potentiation of hsp70 expression observed in aspirin-plus-heat treated rats.
      Given the widespread use of aspirin in humans within a dose range comparable to
      that used here, our findings are likely to have important physiological
      consequences.

PMID- 9250402
TI  - Reactions of protamine with the molecular chaperone DnaK.
AB  - Molecular chaperones of the 70 kDa family mediate protein-protein interactions by
      selectively binding to partially unfolded segments of other proteins in an ATP
      dependent activity cycle. Previous investigations of chaperone substrate
      selectivity have shown that chaperones have a propensity to bind to partially
      unfolded segments of polypeptides that contain bulky hydrophobic residues.
      However, recent investigations have shown that 70 kDa chaperones such as DnaK,
      which is expressed by Escherichia coli, also bind short basic peptides and even
      polycations. We report here that DnaK specifically binds to the polycation
      protamine when [protamine]/[DnaK] is near unity, whereas protamine induces the
      aggregation of DnaK when [protamine]/[DnaK] > or = 20. Complexes between DnaK and
      protamine were detected using fluorescently labeled protamine (protamine*) in
      conjunction with high performance size exclusion chromatography. We found that:
      (i) an unlabeled peptide of known affinity for DnaK partially inhibited the
      formation of DnaK-protamine* complexes; (ii) Mg-ATP (and Mg-gamma-S-ATP)
      significantly reduced the affinity of protamine* for DnaK; and (iii) the rate of
      DnaK-protamine* complex dissociation is highly temperature-sensitive, with
      apparent activation enthalpies (delta H*) equal to 32 +/- 4 and 28 +/- 1 kcal mol
      1 in the absence of added nucleotide and in the presence of ADP, respectively.
      The results are consistent with the specific binding of protamine* at the
      (poly)peptide binding site of DnaK. A model is proposed to account for the
      protamine-induced aggregation of DnaK.

PMID- 9250403
TI  - Herpes simplex virus Us11 protein enhances recovery of protein synthesis and
      survival in heat shock treated HeLa cells.
AB  - One of the herpes simplex virus type 1 (HSV-1) true late gene products, Us11
      protein, is brought into the cell by the infecting virion and may play a role in
      the virally-induced post-transcriptional control of gene expression. Us11 protein
      forms large oligomers, exhibits RNA binding features, concentrates into the
      nucleolus and is able to replace Rex protein in post-transcriptional control of
      human T-cell leukemia/lymphoma virus type I (HTLV-I) expression. As heat shock
      drastically alters protein synthesis, and because HSV-1 infection stimulates heat
      shock protein (Hsp) expression, we analyzed the consequence of heat shock in HeLa
      cells expressing Us11 alone, either transiently or constitutively. No detectable
      modification of the overall pattern of protein synthesis was observed in cells
      growing at normal temperatures, including no induction of Hsp expression or
      accumulation. However, Us11 protein expression induced an enhanced recovery of
      protein synthesis after heat shock. Moreover, the level of Us11 protein-mediated
      protection of protein synthesis was similar to that observed for cells made
      thermotolerant, but only when submitted to a mild heat shock. Finally, Us11
      protein expression induced in cells an enhanced survival to heat shock.

PMID- 9250404
TI  - Major stress protein Hsp70 interacts with NF-kB regulatory complex in human T
      lymphoma cells.
AB  - Polypeptides belonging to the Hsp70 major stress protein family and to the NF
      kB/Rel multi-functional regulatory complex are known to be involved in cellular
      defense mechanisms. It was suggested that both systems may interact in cells that
      respond to injuring stimuli. To check this, Molt4 human lymphoma cells were
      heated at 43 degrees C for 15 min and, after a 6 h post-shock recovery period,
      the cells were activated with phorbol ester or bacterial lipopolysaccharide. It
      was found that mild heat shock caused a substantial increase of the intracellular
      Hsp70 content with the concomitant suppression of NF-kB complexes, though the
      latter was properly activated in non-stressed cells. After a 24 h period of being
      inactive the complex fully recovered its activity and p65 and c-Rel subunits
      migrated to the nucleus. This new active period lasted even longer than that in
      non-heated control cells. As this suggested the existence of a Hsp70-related
      mechanism of NF-kB/Rel complex retention in cytoplasm, we carried out
      immunoprecipitation with the use of anti-Hsp70 and anti-Rel antibodies. All three
      Rel family members p65, c-Rel, p50, but not their precursors and IkB alpha
      inhibitory protein were shown to co-precipitate with the stress protein and anti
      Hsp70 antibodies from both heated and non-heated cells. We conclude that the
      Hsp70 stress protein may confer a new mechanism of NF-kB regulation in cells
      affected by elevated temperature or other factors related to the cellular
      response to stress.

PMID- 9250405
TI  - What structural features determine repair enzyme specificity and mechanism in
      chemically modified DNA?
AB  - A crucial question in repair is how do enzymes recognize substrates. In surveying
      the relevant literature, it becomes evident that there are no rules which can be
      clearly applied. At this time it appears that uracil glycosylase is the only
      repair enzyme for which all the known substrates can be rationalized on the basis
      of chemical structure. When surveying the multiplicity of substrates for m3A-DNA
      glycosylase, it is difficult, on the basis of present knowledge, to explain why
      1,N6-etheno-A (epsilon A) is as good a substrate, if not better, than m3A for
      which the enzyme is named. There is no apparent unifying chemical structure which
      is required for recognition. It should also be noted that many studies of the
      mechanism of m3A-DNA glycosylase only utilized-N-3- and N-7-alkylpurines. On this
      basis, an electron-deficient purine, and later pyrimidine, was considered to be
      the recognition signal. Since epsilon A and Hx do not fall in this class, this is
      one illustration of why exploring new substrates becomes important in elucidating
      enzyme mechanisms. Ubiquitous enzymes, such as 5'-AP endonucleases, are present
      in both prokaryotes and eukaryotes. The primary function is the same, i.e.,
      repair of an AP site which occurs through natural processes or from the action of
      DNA glycosylases. There are, however, completely unrelated substrates such as the
      exocyclic adducts pBQ-dC and pBQ-dG. pBQ-dC is repaired by both the human HAP1
      and E. coli Exo III and Endo IV, while pBQ-dG is only repaired by the E. coli
      enzymes. Yet, when repair of these adducts occurs, it is by the same unusual
      pathway which differs from the usual base excision repair mechanism. This finding
      may ultimately not be as unusual as it now seems. The understanding of substrate
      recognition by repair enzymes, which can have different repair pathways, is
      complex. For example, three exocyclic derivatives which each have either the same
      modification (1,N4-epsilon dA and 3,N4-epsilon dC) or the same base with
      different modifying groups (3,N4-epsilon dC and 3,N4-pBQ-dC) are repaired by
      three separate enzymes and two mechanism (Figure 9). Investigators have also
      reported that two separate enzymes and pathways can be found for simple adducts
      such as m6G and O4T. It is not clear why, for these adducts, both MGMT and
      excision repair can be utilized. This could be visualized as a "backup" system
      and may be more common than now known. We cannot think like an enzyme or vice
      versa. In the absence of enough necessary information, we can only be
      descriptive. What information is necessary for further understanding? (1) More
      detailed structural studies of adducts in defined oligonucleotides would be
      useful. (2) New substrates should be explored. For example, is the mechanism for
      PBQ-dC (and pBQ-dG) repair unique? This involves guesswork and intuition. (3) For
      the adducts mentioned in this Perspective and others, understanding
      enzyme/substrate recognition will be facilitated by cocrystallography and site
      directed mutagenesis. (4) Genetic approaches, such as knockouts or targeted
      mutations in repair genes, should be expanded in order to focus on the
      physiological role of a specific enzyme. Above all: structure, structure,
      structure! Enzymologists, organic chemists, physical chemiste, X-ray
      crystallographers, and others must combine forces if the fundamental problems
      addressed here are to be understood.

PMID- 9250406
TI  - In vitro metabolism of N-(5-chloro-2-methylphenyl)-N'-(2-methylpropyl)thiourea:
      species comparison and identification of a novel thiocarbamide-glutathione
      adduct.
AB  - The in vitro metabolism of SDZ HDL 376, a thiocarbamide developed for the
      treatment of atherosclerosis, was investigated in rat, dog, monkey, and human
      liver microsomes, as well as in rat and human liver slices. [14C]SDZ HDL 376 was
      extensively metabolized in all the species except human. In rat liver microsomes
      an S-oxide was the major metabolite. In human and monkey microsomes, carbon
      hydroxylation was favored. The NADPH-dependent oxidation of SDZ HDL 376 resulted
      in covalent binding to microsomal protein. Addition of GSH to the incubations
      decreased protein binding in a concentration-dependent manner and resulted in a
      novel SDZ HDL 376-GSH adduct. Adduct formation required NADPH and was mediated
      predominantly by cytochrome P450. Inhibition of cytochrome P450 by 1
      aminobenzotriazole resulted in a 95% decrease in adduct formation, while heat
      inactivation of flavin-containing monooxygenases resulted in a 10% decrease.
      Unlike other thiocarbamides which form disulfide adducts with GSH, the SDZ HDL
      376 adduct contained a thioether linkage as characterized by LC/MS/MS and
      reference to a synthetic standard. Reactions performed with [35S]GSH resulted in
      a [35S]SDZ HDL 376-GSH adduct, demonstrating the sulfur was derived from GSH.
      Adduct formation was faster in rat microsomal reactions compared to human
      microsomes. Other structurally unrelated thiocarbamides (phenylthiourea,
      methimazole, 2-mercaptobenzimidazole, 2-mercaptoquinazoline, and 2-propyl-6
      thiouracil) did not form similar adducts in rat liver microsomes supplemented
      with GSH. Therefore, the GSH adduct of SDZ HDL 376 is unique for this type of
      thiocarbamide. These results suggest that the bioactivation and detoxification of
      SDZ HDL 376 differ significantly from other thiocarbamides. Furthermore, the in
      vitro formation of S-oxides and GSH adducts in rat hepatic tissue, and ring
      hydroxylation and glucuronidation in human hepatic tissue, suggests rats may be
      more susceptible to the toxicity of SDZ HDL 376 compared to humans.

PMID- 9250407
TI  - Effects of pH on nonenzymatic oxidation of phenylhydroquinone: potential role in
      urinary bladder carcinogenesis induced by o-phenylphenol in Fischer 344 rats.
AB  - o-Phenylphenol (OPP) and its sodium salt (SOPP) are broad spectrum fungicides and
      antibacterials to which humans are frequently exposed. Both OPP and SOPP have
      been found to cause cancer in the urinary bladder of male F344 rats at high
      doses, and the metabolite phenylhydroquinone (PHQ) is believed to play a key role
      in the carcinogenicity of these compounds. Tumor formation in the treated animals
      has also been shown to be significantly influenced by urinary pH. To provide
      additional insights into the mechanisms of OPP carcinogenesis, we have
      investigated the autoxidation of PHQ over the pH range commonly found in the
      urine of OPP- and SOPP-treated rats. Over the pH range studied (6.3-7.6), a
      curvilinear relationship between rate of PHQ oxidation and pH was observed.
      Phenylbenzoquinone (PBQ) was formed during the autoxidation of PHQ, with a
      formation yield of 0.92 +/- 0.02. In addition, the effects of PBQ and oxygen
      concentrations on PHQ autoxidation and the nonenzymatic conversion of PBQ to PHQ
      were also studied. Our data indicate that the production of reactive metabolites
      from PHQ involves a pH-independent (i.e., oxygen-dependent) and a pH-dependent
      pathway and that the rate of pH-dependent PHQ autoxidation was found to be
      enhanced by the presence of PBQ. A reaction mechanism has been formulated to
      explain the experimental data observed, with ionization of PHQ semiquinone being
      identified as a key step in reactive species production for the pH-dependent
      pathway. By combining data from OPP animal carcinogenicity studies with the
      proposed reaction pathway, a good correlation between the proposed formation of
      reactive species and bladder lesions was observed. These results indicate that
      the pH-dependent autoxidation of free PHQ metabolite in the urine may potentially
      be responsible for the tumorigenic effects of OPP and SOPP observed in the rat
      bladder.

PMID- 9250408
TI  - Oxidation of low-density lipoproteins produces levuglandin-protein adducts.
AB  - Free-radical oxidation of human low-density lipoprotein (LDL) produces
      levuglandin (LG)-protein adducts that were detected with an enzyme-linked
      immunosorbent assay using LGE2-KLH antibodies which recognize LGE2-derived
      pyrroles. The level of immunoreactivity increases with time of oxidation and
      reaches a maximum by 8 h. The yield of pyrrole varies nonlinearly with the level
      of LG adduction to LDL. At low LG:LDL ratios, such as those detected in oxidized
      LDL, the reaction of primary amino groups with LGE2 produces mostly non-pyrrole
      adducts that are not immunoreactive. Concomitant phospholipolysis must occur if
      the generation of immunoreactive epitopes in LDL involves oxidation of
      arachidonyl phospholipids. Thus, since a protein adduct prepared from synthetic
      LGE2-2-lysophosphatidylcholine ester showed, at most, only 0.5% cross-reactivity
      with the LGE2-KLH antibodies, the epitopes detected in oxidized LDL are almost
      certainly not protein adducts of LG-phospholipid esters. As expected, hydrolysis
      of the carboxylic ester in the protein adduct of LGE2-2-lysophosphatidylcholine
      ester by treatment with phospholipase A2 produced a fully immunoreactive LGE2
      protein adduct.

PMID- 9250409
TI  - Estrogen-nucleic acid adducts: reaction of 3,4-estrone-o-quinone radical anion
      with deoxyribonucleosides.
AB  - Metabolic activation of estradiol leading to the formation of catechol estrogens
      is believed to be a prerequisite for its genotoxic effects. Previous studies have
      shown that 3,4-estronequinone (3,4-EQ) can redox-cycle and is capable of inducing
      exclusively single-strand DNA breaks in MCF-7 breast cancer cells [Nutter et al.
      (1991) J. Biol. Chem. 226, 16380-16386]. These studies, however, could not
      provide conclusive evidence about the mechanism of estrogen carcinogenesis. In
      order to explore this in more detail, we have shown previously that 3,4-EQ can
      react with adenine under electrochemical reductive conditions to yield an
      estrogen-nucleic acid adduct [Abul-Hajj et al. (1995) J. Am. Chem. Soc. 117, 6144
      6145]. In this paper, we report the synthesis and identification of nine estrogen
      nucleic acid adducts obtained from reaction of 3,4-EQ with deoxycytidine,
      deoxythymidine, deoxyadenosine, and deoxyguanosine. Purification of reaction
      mixtures using HPLC gave sufficient quantities of reaction products for
      identification using 1H-NMR and mass spectral determinations. Reaction of 3,4-EQ
      with dCyd, dThd, dAdo, and dGuo gave the following estrogen-nucleic acid adducts:
      N4-(4-hydroxyestron-1-yl)deoxycytidine, N4-(4-hydroxyestron-2-yl)deoxycytidine,
      N3-(4-hydroxyestron-1-yl)thymine, N3-(4-hydroxyestron-1-yl)deoxythymidine, N6-(4
      hydroxyestron-1-yl)deoxyadenosine, 8-(4-hydroxyestron-1-yl)adenine, N2-(4
      hydroxyestron-1-yl)deoxyguanosine, 8-(4-hydroxyestron-1-yl)guanine, and 8-(4
      hydroxyestron-2-yl)guanine. Adduction through the NH2 group of dAdo, dGuo, and
      dCyd results in formation of chemically stable adducts. On the other hand,
      adduction at C-8 led to the formation of several depurination adducts identified
      as 4-OHE1-1-C8-Gua, 4-OHE1-2-C8-Gua, and 4-OHE1-1-C8-Ade.

PMID- 9250410
TI  - Mechanism of cytochrome P450-catalyzed aromatic hydroxylation of estrogens.
AB  - The mechanism of aromatic hydroxylation of estrogens by cytochrome P450 enzymes
      has been examined by comparing the oxidation of estrone with that of substrates
      carrying additional aromaticity such as equilenin and the structural analog 2
      naphthol. Hamster liver microsomes preferentially catalyzed the conversion of
      estrone to 2-hydroxyestrone (Km = 30 and 25 microM and Vmax = 1497 and 900 pmol
      (mg of protein)-1 min-1 for 2- and 4-hydroxyestrone formation, respectively). In
      contrast, equilenin was hydroxylated exclusively at C-4 of the steroid ring
      system and 2-naphthol at the corresponding C-1 position (Km = 67 and 42 microM
      and Vmax = 2083 and 3226 pmol (mg of protein)-1 min-1 for 4-hydroxyequilenin and
      1,2-dihydroxynaphthalene formation, respectively). This shift in the specificity
      of hydroxylation was due to the introduction of additional aromaticity at ring B
      of equilenin, because hamster liver microsomes are known not to contain any
      estrogen-4-hydroxylase, only estrogen-2-hydroxylase activity catalyzed by
      cytochrome P450 3A family enzymes. The exclusive 4-hydroxylation of equilenin is
      proposed to be due to a preferred delocalization of the naphthoxy radical an
      intermediate in the hydroxylation, to C-4, whereas delocalization to C-2 requires
      additional activation energy and is energetically not favored. Based on these
      electronic considerations, a mechanism of aromatic hydroxylation of estrogens is
      proposed which features hydrogen abstraction from the phenolic hydroxy group,
      electron delocalization of the phenoxy radical to a carbon-centered radical, and
      subsequent formation of catechol metabolites by hydroxy radical addition at C-2
      or C-4 depending on steric or electronic constraints.

PMID- 9250411
TI  - A cyclic N7,C-8 guanine adduct of N-nitrosopyrrolidine (NPYR): formation in
      nucleic acids and excretion in the urine of NPYR-treated rats.
AB  - N-Nitrosopyrrolidine (NPYR) is a well-established hepatocarcinogen that is
      present in the diet and tobacco smoke and may form endogenously in humans.
      Biomarkers to assess NPYR exposure and metabolic activation in humans are needed.
      The cyclic N7,C-8 guanine adduct 2-amino-6,7,8,9-tetrahydro-9-hydroxypyrido[2,1
      f]purin-4(3H)-one (8), which is formed in tissues of rats treated with NPYR, is
      one potential candidate for such a biomarker. In this study, we evaluated the
      formation of this and other NPYR adducts in reactions of alpha-acetoxyNPYR with
      dGuo, Guo, DNA, and RNA and determined the extent of urinary excretion of adduct
      8 in rats treated with NPYR. alpha-AcetoxyNPYR, a stable precursor to the major
      product of NPYR metabolic activation, was allowed to react with dGuo, Guo, DNA,
      or RNA at 37 degrees C, pH 7. The most striking observation was that the cyclic
      N7,C-8 guanine adduct 8 was formed 9 times more extensively in the reaction with
      Guo than with dGuo. It was also formed 2.5 times more extensively in RNA than in
      DNA. In rats treated with NPYR, levels of the cyclic N7,C-8 guanine adduct 8 were
      2 times as high in RNA than in DNA. Rats treated with [14C]adduct 8 excreted 51%
      of this adduct unchanged in urine. Rats treated with [3,4-3H]NPYR excreted
      0.00004% of the dose as adduct 8. The major differences in product formation in
      reactions of alpha-acetoxyNPYR with dGuo versus Guo are unusual for alkylating
      agents; potential mechanisms are discussed. The higher levels of adduct 8 in RNA
      than in DNA suggest that RNA may be superior as a source of adduct 8 as a
      biomarker.

PMID- 9250412
TI  - Synthesis, characterization, and in vitro quantitation of N-7-guanine adducts of
      diepoxybutane.
AB  - Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene (BD), a high
      volume industrial chemical classified as a probable human carcinogen. Rodent
      inhalation studies show strikingly high sensitivity of mice to carcinogenic
      effects of butadiene compared to rats, which has been linked to differences in
      metabolism. Both species convert BD to 3,4-epoxy-1-butene (EB), but mice further
      oxidize a significantly greater part of EB to DEB. DEB is a potent bifunctional
      genotoxic agent which is 100-fold more mutagenic than EB and is likely to be
      involved in BD-induced carcinogenesis. Identification of specific BD-induced DNA
      adducts is critical to understanding the mechanism of its biological activity. We
      have previously described reactions of EB with guanine and adenine as
      nucleobases, nucleosides, and constituents of DNA. In this work, DEB-induced
      guanine adducts were isolated and structurally characterized by UV spectroscopy,
      mass spectrometry, and nuclear magnetic resonance. When guanosine was reacted
      with DEB in glacial acetic acid followed by hydrolysis in hydrochloric acid,
      three products were isolated: N-7-(2',3',4'-trihydroxybut-1'-yl)guanine (DEB-Gua
      I, major adduct), N-7-(2',4'-dihydroxy-3'-chlorobut-1'-yl)guanine (DEB-Gua II),
      and N-7-(2',3'-dihydroxy-4'-acetoxybut-1'-yl)guanine (DEB-Gua III). We suggest
      initial formation of the N-7-(2'-hydroxy-3',4'-epoxybut-1'-yl)guanine
      intermediate followed by nucleophilic substitution at the 3',4'-epoxy ring with
      hydroxide, chloride, or acetate anions to give DEB-Gua I, II, or III,
      respectively. DEB-Gua I and the epoxy intermediate were also isolated from
      hydrolysates of DEB-exposed calf thymus DNA (CT DNA). N-7-Guanine adducts are
      known to undergo spontaneous and enzymatic depurination producing apurinic sites.
      If not repaired before DNA replication, apurinic sites can give rise to mutations
      and ultimately cancer. The extent of alkylation at the N-7 of guanine in DEB
      exposed DNA (58.7 +/- 1.1 adducts/10(3) normal guanines) was similar to that
      previously reported for CT DNA exposed to EB at the same molar ratio. Since EB
      and DEB appear to induce comparable levels of overall DNA alkylation at the
      conditions applied in this work, other factors, such as formation of DNA cross
      links by DEB but not EB or differences in repair of EB and DEB adducts, may be
      responsible for the differences in mutagenicity.

PMID- 9250413
TI  - Peroxynitrite-mediated decarboxylation of pyruvate to both carbon dioxide and
      carbon dioxide radical anion.
AB  - There has been a recent renewal of interest in the antioxidant properties of
      pyruvate which are usually attributed to its capacity to undergo oxidative
      decarboxylation in the presence of hydrogen peroxide. The interaction of pyruvate
      with other oxidizing biological intermediates, however, has been scarcely
      considered in the literature. Here we report that peroxynitrite, the oxidant
      produced by the reaction between superoxide anion and nitric oxide, reacts with
      pyruvate with an apparent second-order rate constant of 88 +/- 7 M-1 s-1 at pH
      7.4 and 37 degrees C. Kinetic studies indicated that pyruvate reacts with
      peroxynitrite anion (k = 100 +/- 7 M-1 s-1, peroxynitrous acid (k = 49 +/- 7 M-1
      s-1, and a highly oxidizing species derived from peroxynitrous acid. Pyruvate
      decarboxylation was proved by anion exchange chromatography detection of acetate
      in incubations of peroxynitrite and pyruvate at pH 7.4 and 5.5. Formation of
      carbon dioxide radical anion was ascertained by EPR spin-trapping studies in the
      presence of GSH and the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The
      use of pyruvate labeled with 13C at the 1-position led to the detection of the
      labeled DMPO carbon dioxide radical anion adduct. In the absence of GSH, oxygen
      consumption studies confirmed that peroxynitrite mediates the decarboxylation of
      pyruvate to free radical intermediates. Comparing the yields of acetate and free
      radicals estimated from the oxygen uptake studies, it is concluded that pyruvate
      is oxidized by both one- and two-electron oxidation pathways, the latter being
      preponderant. Hydrogen peroxide-mediated pyruvate oxidation does not produce
      detectable levels of carbon dioxide radical anion except in the presence of
      iron(II)-ethylenediamine-N,N,N',N'-tetraacetate (EDTA). The apparent second-order
      rate constant of the reaction between pyruvate and hydrogen peroxide was
      determined to be 1 order of magnitude lower than that of the reaction between
      pyruvate and peroxynitrite. The latter process may contribute to the antioxidant
      properties of pyruvate.

PMID- 9250415
TI  - Toxicity of peroxynitrite and related reactive nitrogen species toward
      Escherichia coli.
AB  - The toxicity of peroxynitrite toward Escherichia coli (expressed as LD50, the
      concentration required to kill 50% of the bacteria) was found to be independent
      of bacterial cell densities over a wide experimental range, spanning 10(6)-10(10)
      colony-forming units/mL; the magnitude of LD50 was also pH-independent over the
      range pH 5.9-8.3. This highly unusual behavior can be quantitatively reproduced
      by a dynamical model in which (i) ONO2H is identified as the toxic form of the
      oxidant and (ii) the bulk of the added peroxynitrite decays to nitrate ion under
      these conditions. From the model, one estimates that 10(6)-10(7) ONO2H molecules
      are required to kill a bacterium, indicating a very high intrinsic toxicity (cf.
      HOCl, for which LD50 = 10(7)-10(8) molecules/cell of E. coli). Nearly complete
      protection was observed when bicarbonate ion was added to the buffer, even when
      concentrations of peroxynitrite exceeded 50 times the LD50 measured in the
      absence of bicarbonate. Consistent with previous reports, combinations of H2O2
      and NO and, in weakly acidic media, H2O2 and NO2- were found to exhibit enhanced
      toxicities relative to the individual reactants. Protection by bicarbonate was
      utilized to assess the potential role of intermediary formation of ONO2H in
      bacterial killing in these systems. Approximately 25% protection by bicarbonate
      was observed for media containing H2O2 and NO2-, consistent with a minor
      contribution to killing by ONO2H under the experimental conditions. No protection
      was observed for media containing H2O2 and *NO in both anaerobic and aerobic
      environments, excluding extracellularly generated ONO2H as a participant in these
      bactericidal reactions.

PMID- 9250414
TI  - Regiospecificity of peroxyl radical addition to (E)-retinoic acid.
AB  - The regiochemistry of peroxyl radical addition to (E)-retinoic acid (RA) was
      investigated. Peroxyl radicals, generated by reaction of 13-hydroperoxy-(9Z,11E)
      octadecadienoic acid with hydroxo(porphyrinato)iron(III) in Tween 20 micelles,
      were reacted with RA. The major, and virtually exclusive, RA oxidation product
      was 5,6-epoxy-RA which was identified on the basis of cochromatography with the
      synthetic synthetic oxirane (in a reverse phase HPLC system), electronic
      absorption spectroscopy, high-field 1H-NMR, and EI mass spectrometry. These
      results suggest that peroxyl radicals react with RA by regioselective addition to
      either C5 or C6 yielding an endocyclic tertiary allylic or tertiary carbon
      centered radical adduct, respectively. Subsequent beta-elimination of an alkoxyl
      radical yields the oxirane. Computational studies were carried out in order to
      gain mechanistic insights into the observed regiospecificity of the peroxyl
      radical-dependent epoxidation reaction; molecular mechanics and semiempirical
      quantum mechanical calculations were carried out using Tripos force field
      parameters and AM1, respectively. The results suggest that the regiospecific
      epoxidation may be influenced by the 5,6-olefinic function behaving as a
      partially-isolated double bond as well as inherent allylic A1,2 strain in the
      substituted cyclohexene ring as a consequence of substitutions at C1 and C6. In
      addition, calculated heats of formation indicated preferential peroxyl radical
      addition to C5 versus C6; this may reflect differences in the geometries of sp2
      orbitals containing the radical densities rather than resonance contributions by
      the highly conjugated polyene system.

PMID- 9250416
TI  - Cysteine conjugate beta-lyase-dependent biotransformation of the cysteine S
      conjugates of the sevoflurane degradation product 2-(fluoromethoxy)-1,1,3,3,3
      pentafluoro-1-propene (compound A).
AB  - 2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (1, Compound A) is a
      fluoroalkene formed by the base-catalyzed degradation of sevoflurane that is
      nephrotoxic in rats. Fluoroalkene 1 is a structural analog of other nephrotoxic
      haloalkenes that undergo glutathione S-conjugate formation and cysteine S
      conjugate beta-lyase-dependent bioactivation to reactive intermediates. The
      present experiments were designed to study the beta-lyase-dependent
      biotransformation of S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine
      (4) and S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-L-cysteine (5) by
      19F NMR and UV spectroscopy and GC/MS. Incubation of cysteine S-conjugate 4 with
      rat kidney cytosol or a pyridoxal model system showed the formation of inorganic
      fluoride, pyruvate, and 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid (9), the
      expected products of a beta-lyase-catalyzed reaction. The ratio of fluoride to
      pyruvate ranged from 2.3 to 2.5. The amount of acid 9 formed in the rat kidney
      cytosol and the pyridoxal model system was, however, less than 5% of the amount
      of pyruvate formed. Incubation of conjugate 4 with rat kidney cytosol and
      analysis by 19F NMR spectroscopy showed resonances that were assigned to 3,3,3
      trifluorolactic acid (10); the formation of acid 10 was observed in the pyridoxal
      model only after prolonged incubation (> 18 h). Lactic acid 10 was identified as
      a degradation product of acid 9. Cysteine S-conjugate 5 was not stable in pH 7.4
      buffer and underwent a rapid cyclisation reaction (t1/2 approximately 5 min) to
      form 2-[1-(fluoromethoxy)-2,2,2-trifluoroethyl]-4,5-dihydro-1,3-thiazol e-4 
      carboxylic acid (14). These data show that fluoroalkene 1-derived cysteine S
      conjugates are substrates for renal beta-lyase and that acid 9 is formed as a
      terminal product. Acid 9 is, however, unstable and affords lactic acid 10 as a
      degradation product.

PMID- 9250417
TI  - Photophysical and photochemical characterization of a photosensitizing drug: a
      combined steady state photolysis and laser flash photolysis study on carprofen.
AB  - Carprofen (1a) is a photosensitizing nonsteroidal anti-inflammatory drug. It
      undergoes photodehalogenation from its triplet excited state. The resulting aryl
      radical (II) is able to abstract hydrogen atoms from model lipids, mediating
      their peroxidation by a type I mechanism. This aryl radical intermediate appears
      to be responsible for the observed photobiological effects of carprofen. The
      active involvement of the triplet state has been confirmed by direct detection of
      this species in laser flash photolysis and by quenching experiments with
      cyclohexadiene and naphthalene. Carprofen also photosensitizes singlet oxygen
      production with a quantum yield of 0.32. A minor reaction pathway is
      photodecarboxylation, which occurs from the excited singlet state and leads to an
      acetyl derivative (1b). In the case of the dehalogenated photoproduct (2a),
      photodecarboxylation to the ethyl (2d) and acetyl (2b) derivatives, together with
      singlet oxygen production (quantum yield = 0.18), is also possible. However, the
      biological activity of 2a in the linoleic acid photoperoxidation and
      photohemolysis tests is markedly lower than that of 1a, which constitutes further
      evidence in favor of the important role of photodehalogenation in the adverse
      photobiological effects of carprofen.

PMID- 9250418
TI  - Mobilization of iron from urban particulates leads to generation of reactive
      oxygen species in vitro and induction of ferritin synthesis in human lung
      epithelial cells.
AB  - Many of the biochemical effects of asbestos in cultured cells have been shown to
      be due to iron, which can be as high as 27% by weight. Urban air particulates
      also contain iron, and some of the pathological effects after inhalation may be
      due to reactive oxygen species produced by iron-catalyzed reactions. Two standard
      reference material (SRM) urban air particulate samples were used for the studies
      described here. SRM 1648 (3.9% iron by weight) was collected in the St. Louis,
      MO, area, and SRM 1649 (3% iron by weight) was collected in the Washington, DC,
      area. To determine if iron associated with urban particulates could be mobilized,
      as it is from asbestos, SRMs 1648 and 1649 were incubated with 1 mM citrate or
      EDTA, in the presence or absence of ascorbate. Iron was mobilized from both
      particulates by either chelator, especially in the presence of ascorbate.
      Citrate, in the presence of ascorbate, mobilized 30.9 nmol of Fe/mg of SRM 1648
      and 65.1 nmol of Fe/mg of SRM 1649 in 24 h. EDTA, in the presence of ascorbate,
      mobilized 53.8 nmol of Fe/mg of SRM 1648 and 98.8 nmol of Fe/mg of SRM 1649 in 24
      h. To determine whether reactive oxygen species were being produced by the
      particulate iron, each particulate was incubated with phi X174 RFI DNA in the
      presence or absence of ascorbate. Single-strand breaks (SSBs) were produced by
      either particulate, but only in the presence of ascorbate. Incubation of SRM 1648
      or 1649 (0.5 mg/mL) with DNA in the presence of ascorbate and citrate resulted in
      20% or 34% DNA with SSBs, respectively. Incubation of SRM 1648 or 1649 (0.1
      mg/mL) with DNA in the presence of ascorbate and EDTA resulted in 26% or 45% DNA
      with SSBs, respectively. To determine if iron associated with urban particulates
      could be mobilized by human lung epithelial cells (A549), cells were treated with
      particulates and the amount of the iron storage protein ferritin was determined
      at the end of treatment. The 6.4- or 8.4-fold increase in ferritin observed in
      cells treated with SRM 1648 or 1649, respectively, over that of control
      (untreated) cells strongly suggested that iron was mobilized in the cultured
      cells. If similar mobilization and reactivity of the iron occurs in the lung,
      this may explain some of the pathological effects of urban particulates.

PMID- 9250419
TI  - Individual bioequivalence. New concepts in the statistical assessment of
      bioequivalence metrics. FDA Individual Bioequivalence Working Group.

PMID- 9250420
TI  - Clinical pharmacokinetics of mifepristone.
AB  - Mifepristone is a steroidal antiprogestin and antiglucocorticoid acting at the
      receptor level. The aromatic dimethylaminophenyl side chain in position 11 of the
      steroid structure is essential for the antagonistic properties of mifepristone.
      The pharmacokinetics of mifepristone are characterised by rapid absorption, a
      long half-life of 25 to 30 hours and micromolar serum concentrations following
      ingestion of doses currently in clinical use. The serum transport protein alpha 1
      acid glycoprotein (AAG) regulates the serum kinetics of mifepristone. Binding to
      AAG limits the tissue availability of mifepristone, explaining the low metabolic
      clearance rate of 0.55 L/kg/day and the low volume of distribution of
      mifepristone. Also, similar serum concentrations of mifepristone following
      ingestion of single doses exceeding 100mg can be explained by saturation of the
      binding capacity of serum AAG. Following oral intake, mifepristone is extensively
      metabolised by demethylation and hydroxylation, the initial metabolic steps are
      catalysed by the cytochrome P450 (CYP) enzyme CYP3A4. The 3 most proximal
      metabolites, namely the monodemethylated, didemethylated and hydroxylated
      metabolites of mifepristone, all retain considerable affinity toward the human
      progesterone and glucocorticoid receptors; in addition, the serum concentrations
      of these 3 metabolites are in a similar range as those of the parent drug. Thus,
      the combined pool of mifepristone, as well as that of the metabolites, seems
      responsible for the biological actions of mifepristone. Combination therapy with
      mifepristone and low dose prostaglandin is currently in clinical use for
      termination of early pregnancy in China, France, Sweden and the UK. The combined
      regimen is well tolerated and highly efficacious with a 95% rate of complete
      pregnancy terminations. Recent clinical studies on pregnancy termination have
      focused on dose optimisation of mifepristone and evaluation of the orally active
      prostaglandin derivative misoprostol. In addition, several other indications for
      the clinical use of mifepristone, such as induction of labour, contraception, as
      well as treatment of various hormone dependent disorders, are emerging. The major
      obstacles currently inhibiting further evaluation and distribution of
      mifepristone are political rather than clinical. However, it is hoped that the
      eventual introduction of new antiprogesterone molecules by several manufacturers
      will enhance the availability of this important class of new drugs.

PMID- 9250421
TI  - The role of beta-glucuronidase in drug disposition and drug targeting in humans.
AB  - Glucuronides of drugs often accumulate during long term therapy. The hydrolysis
      of glucuronides can be catalysed by beta-glucuronidase, an enzyme expressed in
      many tissues and body fluids in humans. The possible contribution of beta
      glucuronidase to drug disposition in humans has not been assessed in a systematic
      manner, but this enzyme may be able to release, locally or systemically, the
      active or inactive parent compound from drug glucuronides, thereby modifying the
      disposition and action of these drugs. Based on the information available on the
      localisation, expression and variability of beta-glucuronidase, the concept of
      beta-glucuronidase-mediated drug metabolism is outlined in this article using
      examples from the literature. Since some issues surrounding the beta
      glucuronidase-mediated deconjugation of drug glucuronides still need to be
      clarified in humans, additional data from animal models supporting this concept
      have been included. Moreover, as beta-glucuronidase has already been proven to be
      useful in tumour specific bioactivation of glucuronide prodrugs of anticancer
      agents, we also focus on anticancer prodrug approaches utilising beta
      glucuronidase. This review summarises the role of beta-glucuronidase in drug
      disposition and drug targeting in humans.

PMID- 9250422
TI  - Pharmacokinetics and administration regimens of vancomycin in neonates, infants
      and children.
AB  - The increased use of vancomycin in neonatal and paediatric patients has prompted
      numerous pharmacokinetic studies and the development of many empirical
      administration methods. The majority of dosage guidelines use the relationship
      between pharmacokinetic parameters and patient variables such as chronological
      age, bodyweight, and/or measures of renal function. Currently, those dosage
      guidelines which are based upon postconceptional age and bodyweight seem to
      provide the best options for empirical administration in neonates and infants. In
      addition, serum creatinine may prove to be a useful guide to the empirical
      administration of vancomycin in neonates older than 7 to 14 days. Several
      investigators have reported the individualisation of dosage regimens based on
      pharmacokinetic-based administration methods. The most common techniques employed
      have been Sawchuk-Zaske method and Bayesian forecasting. However, only a limited
      number of studies have evaluated either empirical administration or
      individualised administration techniques in patient populations outside those of
      the original reports; this makes choosing between the methods difficult.
      Pharmacokinetic data and administration recommendations have gradually become
      available in special paediatric patient populations. The majority of studies have
      focused on patients requiring cardiopulmonary bypass surgery or with burns,
      cancer or central nervous system infections. However, a limited amount of
      information is available regarding vancomycin disposition in children older than
      1 year of age with and without end-stage renal failure. The monitoring of serum
      vancomycin concentrations may be useful in selected neonatal and paediatric
      patient populations, especially where large interpatient variability occurs and
      administration guidelines are not clearly established. Similar to the literature
      on adults, the lack of conclusive evidence concerning the relationship between
      serum vancomycin concentrations and therapeutic responses leaves this topic open
      to debate.

PMID- 9250424
TI  - Anticipatory planning for psychiatric treatment is not quite the same as planning
      for end-of-life care.

PMID- 9250426
TI  - Neighbors' perceptions of group homes.
AB  - Neighbors often presume that group homes (GHs) have negative effects on their
      neighborhoods, but it is rather unclear how often GHs actually have adverse
      effects. Neighbors of GHs and a matched set of people who did not live near GH
      were interviewed. Neighbors of GHs were asked about their experiences with the
      specific GH near them, while "non-neighbors" were asked similar questions about
      their expectations of what it would be like to live near a GH. For both negative
      (e.g., noise, traffic) and positive effects (e.g., leaning about disabilities) of
      GHs, non-neighbors expected GHs would have a much greater impact on them than
      what was actually reported by neighbors. This research supports prior findings
      that expectations of negative effects are much greater than what is actually
      experienced by neighbors. It also suggests that GH operators might wish to
      capitalize on the positive expectations that may be over-shadowed by the more
      commonly voiced negative expectations.

PMID- 9250425
TI  - Predictors of depressive symptomatology among lower social class caregivers of
      persons with chronic mental illness.
AB  - This study examined the predictors of depressive symptomatology among caregivers
      of persons with chronic mental illness. Data were collected through in-person
      interviews with family caregivers of 103 adults with chronic mental illness who
      were served by mental health case management agencies. The results indicated that
      insufficiency of overall social support was the most powerful predictor of
      caregiver depressive symptomatology. In addition, caregiver burden had a
      significant unique contribution to caregiver depressive symptomatology, with
      higher levels of burden associated with greater levels of caregiver depressive
      symptomatology. Higher levels of client behavioral problems and insufficient
      support from family members and mental health professionals related to the
      caregiving role were associated with higher levels of caregiver depressive
      symptomatology through their associations with caregiver burden. Caregiver race
      was not significantly related to caregiver burden or to caregiver depressive
      symptomatology after controlling for other variables. Over two-fifth of White
      caregivers and over one-quarter of Black caregivers were at risk for clinical
      depression. Implications for practice and research are discussed.

PMID- 9250427
TI  - Trends in siting strategies.
AB  - The ethics and efficacy of notifying neighbors in advance of the establishment of
      group housing for the chronically mentally ill has generated much controversy,
      and recent federal anti-discrimination legislation has supported its
      discontinuation. In this study, representatives from 72 Massachusetts mental
      health agencies were interviewed regarding the siting strategies used in their
      most recent group housing development, and the community responses to that site.
      A majority of agencies were found to have used advance notification, and there
      was a significant association between notifying neighbors and community
      opposition. Agencies using advance notification were also significantly more
      likely to initiate post-siting community outreach activities.

PMID- 9250429
TI  - Preparing psychiatric rehabilitation specialists through undergraduate education.
AB  - This report outlines the development of a new undergraduate psychiatric
      rehabilitation curriculum designed to prepare students for entry-level positions.
      The program, which opened in January 1993, has graduated 25 students with
      Associate of Science degrees in Psychiatric Rehabilitation as of May 1995. The
      need for the program, a brief overview of its curriculum, and the evaluation of
      its impact on students and agencies are presented.

PMID- 9250428
TI  - Rural-urban differences in psychiatric status and functioning among clients with
      severe mental illness.
AB  - Studies of clients with severe mental illness (SMI) typically focus on
      individuals in larger urban areas. Less is known about clients in rural and
      smaller urban areas. Here we compare the psychiatric status, home and community
      activities of daily living, and social and vocational functioning of 1600 adult
      clients with SMI from 18 small-city and rural Wisconsin counties. Rural clients
      are less likely to have a diagnosis of schizophrenia or organic brain syndrome;
      have higher levels of general pathology, including more belligerent, bizarre,
      nervous, and depressive behaviors; and engage in fewer vocational activities than
      urban clients.

PMID- 9250423
TI  - Clinical pharmacokinetics of fluconazole in superficial and systemic mycoses.
AB  - The bis triazole agent fluconazole is used widely in the treatment of superficial
      and deep mycoses. A single oral dose of fluconazole 150 mg gives a mean long term
      clinical cure rate of 84 +/- 5% and is considered a valuable alternative to other
      topical antifungal drugs for vaginal candidiasis. A clinical cure rate of 90.4%
      for oropharyngeal candidiasis was obtained with 100mg daily for a minimum of 14
      days; however, as for the other azoles the rate of relapse was large (40%) in
      immunocompromised patients. A daily dose of 100mg for at last 3 weeks gave
      satisfying outcomes for oesophageal candidiasis. Most patients (71 to 86%) with
      signs and symptoms of urinary tract candidiasis show beneficial clinical results
      when given oral fluconazole 50mg for several weeks. Fluconazole 50 to 150 mg
      given for weeks or months results in over 90% clinical cure or improvement for
      cutaneous mycosis including tinea, pityriasis, cryptococcosis and candidiasis.
      Prolonged (6 to 12 months) fluconazole 150 mg once a week is needed to treat
      onychomycosis successfully. Higher oral doses (200 to 400 mg daily) for long
      periods are generally used to treat deep mycoses such as meningitis,
      ophthalmitis, pneumonia, hepatosplenic mycosis and endocarditis. Fluconazole is
      effective for treating the fungal peritonitis which can complicate continuous
      ambulatory peritoneal dialysis (CAPD). A regimen of 50 mg intraperitoneally or
      100 mg orally was used in these patients with impaired renal function. The dosage
      schedules used to treat disseminated fungal infections due to systemic mycoses
      with different or multiple foci of infections vary widely, with doses of 50 to
      400 mg given orally or intravenously for between 1 week and several months. The
      most recent clinical reports have investigated the use of prophylaxis with
      fluconazole 100 to 400 mg daily, in immunocompromised patients. Fluconazole is
      found in body fluids such as vaginal secretions, breast milk, saliva, sputum and
      cerebrospinal fluid at concentrations comparable with those determined in blood
      after single or multiple doses. There is an excellent linear plasma concentration
      dose relationship, but the mycological and clinical responses do not appear to be
      well correlated with the dose. A total maximum daily dose of 1600 mg is
      recommended to avoid neurological toxicity. Data from pharmacokinetic studies
      conducted in patients, mainly those with AIDS, and using a 1-compartment model
      give very constant parameters similar to those obtained in healthy individuals.
      Bioavailability, measured in HIV-positive patients and those with AIDS, exceeded
      93% for tablets, suspension and suppositories. The time to reach peak plasma
      concentrations (tmax) was 2.4 to 3.7 hours. The peak plasma drug concentration
      (Cmax) obtained after a 100 mg oral dose was 2 mg/L. Areas under the
      concentration-time curve (AUC) obtained in different studies all correlate well
      with the dose (r = 0.926). The AUC determined after 200 and 25 mg suppositories
      were similarly well correlated. Hypochlorhydria does not affect the absorption of
      fluconazole, neither does food intake, race (Japanese or Caucasian) or
      gastrointestinal resection. Binding to plasma protein is low (11.14%) and is
      increased to 23% in cancer patients. Fluconazole is rapidly distributed to the
      tissue, where it accumulates. Tissues fall into 1 of 4 groups of increasing drug
      concentration: blood, bone and brain have the lowest concentrations, and spleen
      has the highest. The volume of distribution (Vd) remains stable at 46.3 +/- 7.9L
      and is considered to be an 'invariant' parameter across species. Fluconazole is
      poorly metabolised and is mainly eliminated unchanged in the urine. The
      percentage of the dose recovered in the urine in 48 hours is close to 60%.
      Concentrations in the urine are high and the half-life (t1/2) is long (37.2 +/-
      5.5h) in patients, mainly those with AIDS, which is not significantly different
      from the t1/2 (31.4 +/- 4.7 hours) in healthy individuals. (ABSTRACT TRUN

PMID- 9250430
TI  - Domestic violence intervention in an urban Indian health center.
AB  - This report describes a domestic violence program in an urban Indian health
      center. The failure of office-based interventions and the importance of
      developing interventions that are sensitive to the needs of this population are
      discussed. Successful interventions including home visits and a domestic violence
      group that incorporated American Indian traditions and values are presented.

PMID- 9250433
TI  - Extent of sexual abuse.

PMID- 9250434
TI  - Discriminating between generalized anxiety disorder and anxiety disorder not
      otherwise specified in a Hispanic population: is it only a matter of worry?
AB  - One hundred and two Hispanic persons who presented for treatment at a specialized
      anxiety disorders clinic were evaluated at intake using the Anxiety Disorders
      Interview Schedule-Revised (ADIS-R; DiNardo and Barlow [1988] Albany: Center for
      Stress and Anxiety Disorders, State University of New York at Albany). Results
      indicated that 14% of these patients suffered from anxiety and/or affective
      disorders that were not adequately captured by our current diagnostic system.
      Given that the majority of these cases were characterized by predominantly
      anxious features, further investigation was undertaken to determine the degree of
      overlap between these patients (anxiety disorder, not otherwise specified; NOS)
      and those with generalized anxiety disorder (GAD). The two groups differed only
      with regard to the number of excessive worries they reported and not in terms of
      somatic symptomatology, psychosocial stressors, or demographic variables. These
      data suggest that excessive worry may be a discriminating factor between the GAD
      and NOS groups, providing support for the notion of GAD as a disorder of chromic
      worry. Future research is needed to tease apart the relative influences of
      culture and socioeconomic status on our findings.

PMID- 9250435
TI  - Recall of family factors in social phobia and panic disorder: comparison of
      mother and offspring reports.
AB  - Previous research has indicated that adults with various anxiety disorders,
      especially social phobia, recall their parents as excessively protective and
      controlling and as low in socialization. However, it is not clear whether such
      results would be supported by parents. In the present study subjects with social
      phobia, panic disorder, and nonclinical subjects and their mothers were given
      parallel measures of maternal control, socialization, and offspring early
      introverted behaviors as well as several questions relating to two early major
      life events and family size. Anxious offspring reported the usual high maternal
      control and low paternal socialization and mother supported the data on
      socialization. On control, mothers provided mixed results, disagreeing on a more
      standard measure, but showing agreement on a more operationalized measure. The
      data were more consistent for social phobia than for panic disorder. In terms of
      early life factors, both anxiety disorders were associated with fewer friends and
      more introverted behaviors, while family size and two major life events did not
      differentiate groups.

PMID- 9250431
TI  - Evaluation of brain injury related behavioral disturbances in community mental
      health centers.
AB  - As a result of improved emergency trauma services, more individuals suffering a
      traumatic brain injury are surviving. Unfortunately, most of these survivors
      suffer chronic neuropsychiatric sequelae related to both the brain damage and the
      psychosocial impact of the injury on self-esteem, self-image, primary role, and
      vocational function. Current community supports are often inadequate to deal with
      the complex array of neurologic and psychiatric difficulties. This article
      outlines common features of brain injury, explores the link between these
      features and the common neuropsychiatric sequelae of brain injury, and suggests
      some principles helpful in the evaluation of the behaviorally challenged brain
      injured patient.

PMID- 9250436
TI  - Panic disorder versus panic disorder with major depression; defining and
      understanding differences in psychiatric morbidity.
AB  - The present study examined the impact of comorbid major depressive disorder (MDD)
      on psychiatric morbidity, panic symptomatology and frequency of other comorbid
      psychiatric conditions in subjects with panic disorder (PD). Four hundred thirty
      seven patients with PD were evaluated at intake as part of a multicenter
      longitudinal study of anxiety disorders; 113 of these patients were also in an
      episode of MDD. Patients were diagnosed by DSM-III-R criteria utilizing
      structured clinical interviews. The 113 PD/MDD patients were compared with the
      324 remaining PD subjects regarding panic symptoms at intake, sociodemographic,
      quality of life and psychiatric morbidity variables. Differences in frequency of
      other comorbid Axis I psychiatric disorders were assessed at intake; personality
      disorders were evaluated twelve months after intake. The results revealed the
      PD/MDD patients exhibit increased morbidity and decreased psychosocial
      functioning as compared to PD patients. Personality disorders were more prevalent
      in the PD/MDD group at six month follow-up assessment; the PD/MDD group also had
      an increased frequency of posttraumatic stress disorder (PTSD) and more comorbid
      Axis I anxiety disorders as compared to the PD group. The total number and
      frequency of panic symptoms was highly consistent between the two patient groups.

PMID- 9250437
TI  - Effects of intravenous caffeine administered to healthy males during sleep.
AB  - Pharmacological challenge paradigms have been useful for elucidating the
      phenomenology and neurobiology of panic attacks. A drawback of the
      pharmacological challenge method is that individual differences in baseline
      arousal and outcome expectancy can lead to different subjective and physiological
      drug responses. One method for eliminating differences in baseline arousal and
      expectancy is to perform pharmacological challenges during non-rapid eye movement
      (non-REM) sleep. In the present study, fourteen healthy male volunteers received
      caffeine (5 mg/kg) and placebo (normal saline) during non-REM sleep on two
      successive nights, in a single-blind manner. Caffeine, compared to placebo, was
      associated with increased arousal, sleep disruption, and elevations in
      adrenocorticotropic hormone (ACTH) and cortisol. In one subject, caffeine
      infusion during sleep induced a panic attack. These findings indicate that
      caffeine leads to increased arousal and hypothalamic-pituitary-adrenal axis (HPA)
      axis activation in the absence of high baseline anxiety and expectancy bias.
      Further, they suggest that similar techniques can be employed in patient
      populations to elucidate the neurobiology of sleep panic attacks.

PMID- 9250438
TI  - Acute effects of ketamine in the holeboard, the elevated-plus maze, and the
      social interaction test in Wistar rats.
AB  - Although noncompetitive NMDA receptor antagonists have shown an anxiolyticlike
      profile in several studies, such effects have not been observed consistently.
      Previous studies with ketamine, a noncompetitive NMDA antagonist, have employed
      only shock tests of anxiety based on conflict procedures. In the present
      experiment, the effect of an acute low dose of ketamine (7 mg/kg) was examined in
      adult male Wistar rats tested in three nonconflict tests: holeboard, social
      interaction, and elevated plus-maze paradigms. The results showed that ketamine
      decreased time spent in active social interaction and the number of rearings and
      central activity in the social interaction test. It also decreased the number of
      entries into the percentage of time spent in open arms and the total number of
      entries in the elevated plus-maze. No significant effect was observed in head
      dipping in the holeboard test, although the number of crossings did increase.
      These results suggest an anxiogeniclike effect of ketamine in contrast with
      results previously described for noncompetitive NMDA receptor antagonists. These
      effects of ketamine are more similar to those described for stimulant drugs such
      as caffeine, cocaine, or amphetamine in anxiety tests.

PMID- 9250439
TI  - Psychotic features and combat-associated PTSD.
AB  - Psychotic symptoms and psychotic disorder diagnoses have occasionally been
      reported in association with chronic posttraumatic stress disorder (PTSD).
      Although psychotic features may be related to core PTSD symptoms, i.e., part of
      the reexperiencing phenomena, it is possible that they are secondary to certain
      comorbid disorders which are also prevalent in this patient population, e.g.
      major depression or substance abuse. In a prospective study, combat associated
      PTSD patients (n = 25) were administered clinical ratings, including the
      Structured Clinical Interview for DSM-III-R with psychotic screen (SCID-P),
      Clinician Administered PTSD Scale (CAPS) and the Impact of Events Scale (IES).
      Thirty-six percent (n = 9) endorsed psychotic symptoms with associated
      comorbidity including: major depressive episode, bipolar disorder, alcohol or
      polysubstance abuse panic disorder, and phobias. All but one of the patients with
      psychotic features also met criteria for major depressive episode. None had a
      primary psychotic disorder diagnosis. There were no significant differences in
      total CAPS scores between patients with or without psychotic features (82.6 +/-0
      17.6 versus 75.3 +/- 22.4, p ns), nor for the different symptom cluster
      subscales. There were also no differences in the IES scores between groups (34.8
      +/- 10 versus 32.6 +/- 10 p ns). This suggests that these psychotic features may
      not necessarily reflect severity of PTSD symptoms. PTSD may share a common
      diathesis with mood disorders including psychotic depression. Further study is
      needed of these phenomena.

PMID- 9250440
TI  - Dysmorphobia group treatment.

PMID- 9250441
TI  - Current knowledge and research directions in the treatment of paruresis.

PMID- 9250442
TI  - "Stress control" large group therapy: implications for managed care systems.

PMID- 9250443
TI  - Whither lipoprotein(a): is this lipid subclass a causative or predictive factor
      in diabetic macrovascular disease?

PMID- 9250444
TI  - IDDM, counterregulation, and the brain.

PMID- 9250445
TI  - Alanine and terbutaline in the prevention of nocturnal hypoglycemia in IDDM.
AB  - OBJECTIVE: To test the hypothesis that because of sustained glycemic actions,
      bedtime administration of the glucagon-releasing amino acid alanine or the
      epinephrine-simulating beta2-adrenergic agonist terbutaline more effectively
      prevents nocturnal hypoglycemia than a conventional bedtime snack, we studied 15
      patients with IDDM. RESEARCH DESIGN AND METHODS: On each of four occasions, the
      same individualized dose of NPH insulin (0.1-0.2 U/kg) was administered with
      either no treatment (control) or, in random sequence, oral treatment with a snack
      (240 ml of 2% milk plus one slice of toast, approximately 200 kcal), alanine (40
      g, plus 10 g of glucose, approximately 200 kcal), or terbutaline (5.0 mg) at
      2200. RESULTS: During the first half of the night (2315-0300), mean plasma
      glucose concentrations were higher after the snack (P < 0.02), alanine plus
      glucose (P < 0.01), or terbutaline (P < 0.001), compared with no treatment.
      During the second half of the night, mean plasma glucose levels were no different
      from control values (73 +/- 5 mg/dl, 4.1 +/- 0.3 mmol/l) after the snack (73 +/-
      7 mg/dl, 4.1 +/- 0.4 mmol/l), tended to be higher after alanine plus glucose (96
      +/- 16 mg/dl, 5.3 +/- 0.9 mmol/l), and were significantly higher after
      terbutaline (124 +/- 15 mg/dl, 6.9 +/- 0.8 mmol/l, P < 0.01). Nocturnal plasma
      glucose levels of 40 mg/dl (2.2 mmol/l) or less (which were treated with
      intravenous glucose) occurred on 13 occasions in seven patients in the control
      arm and 10 occasions in six patients in the snack arm (not significantly
      different from the control arm), but on only 1 occasion in the alanine-plus
      glucose arm (P < 0.02) and the terbutaline arm (P < 0.02). CONCLUSIONS: In
      patients with IDDM given an evening dose of NPH insulin, a conventional bedtime
      snack exerts an inconsistent glycemic effect only during the first half of the
      night, and bedtime administration of the glucagon-releasing amino acid alanine or
      the epinephrine-simulating beta2-adrenergic agonist terbutaline more effectively
      prevents nocturnal hypoglycemia than a conventional bedtime snack.

PMID- 9250446
TI  - Mortality of childhood-onset IDDM patients. A cohort study in Havana City
      Province, Cuba.
AB  - OBJECTIVE: To determine the survival pattern and the underlying cause of death in
      a cohort of childhood-onset IDDm subjects from Havana City Province, Cuba.
      RESEARCH DESIGN AND METHODS: This was a descriptive study carried out on a
      historical cohort of IDDM subjects with disease onset before 15 years of age in
      Havana City Province, Cuba. The cohort was assembled from several sources.
      Subjects were diagnosed from 1965 to 1980, and their vital status was assessed at
      31 December 1991. Cumulative survival rate was calculated by the Kaplan-Meier
      method, and a univariate analysis was performed. To test survival differences
      between groups, the Cox-Mantel test was used. To compare the cohort mortality
      with the general population, standardized mortality ratios by sex and age were
      calculated. Specific causes of death were determined by a committee examining
      death certificates, clinical records, and necropsy reports. RESULTS: A total of
      504 subjects were identified, and the mean follow-up time was 17.5 years. Of the
      subjects, 70 (13.9%) had died at 31 December 1991. Overall, the cohort had a 71%
      cumulative survival rate at 25 years of IDDM duration. There were no survival
      differences according to sex or calendar period of IDDM diagnosis. Statistically
      significant differences were found among age-at-diagnosis groups. The group with
      a peripubertal age at diagnosis showed the worst prognosis. The cohort
      experienced 8.5 times the all-causes death rate, compared with the general
      population. Renal disease accounted for almost half the deaths. CONCLUSIONS: IDDM
      subjects from Havana City Province, Cuba, showed a better survival pattern than
      IDDM subjects from other developing countries. However, when compared with IDDM
      populations from developed countries, there is a survival reserve to be achieved
      by reducing mortality due to renal disease and infections.

PMID- 9250447
TI  - Serum insulin and lipoprotein(a) concentrations. The Jichi Medical School Cohort
      Study.
AB  - OBJECTIVE: To examine the relationship between serum insulin and lipoprotein (a)
      [Lp(a)] concentrations in both sexes in a large population. RESEARCH DESIGN AND
      METHODS: The authors conducted a cross-sectional investigation of fasting serum
      concentrations of insulin and Lp(a), other blood tests, blood pressures,
      anthropological measurements, physical activity index, smoking habit, alcohol
      consumption, and menopause. The subjects were 1,121 men and 1,480 women, ranging
      between 30 and 90 years of age, who were voluntary participants in the Jichi
      Medical Cohort Study and who resided in one of five rural communities in Japan.
      RESULTS: In men, insulin, age, BMI, LDL cholesterol, triglycerides, glucose, and
      fibrinogen were significantly correlated with Lp(a). In women, insulin, age, LDL
      cholesterol, fibrinogen, and activated coagulation factor VII were significantly
      correlated with Lp(a). However, all correlations were weak in either sex. Insulin
      was inversely correlated with Lp(a) in both sexes. However, the coefficients were
      weak (r = -0.16 in mean and r = -0.06 in women). In the partial correlation
      analyses, Lp(a) was not significantly associated with insulin in either sex. The
      result was not influenced by selecting the subjects on the basis of detectable
      values of insulin and Lp(a) and stratifying them by serum glucose level.
      CONCLUSIONS: There was no significant relationship found between serum insulin
      and Lp(a) concentrations in either sex of the cohort, which indicates that Lp(a)
      does not play a role in the increased risk of cardiovascular disease in
      hyperinsulinemic subjects.

PMID- 9250448
TI  - The role of late-onset autoimmune diabetes in white familial NIDDM pedigrees.
AB  - OBJECTIVE: To determine whether autoimmunity is a prominent feature of NIDDM
      among diabetic members in families with a strong history of NIDDM or in families
      with a mixture of NIDDM and IDDM. RESEARCH DESIGN AND METHODS: We determined GAD
      and islet cell (ICA512) autoantibodies from 215 NIDDM individuals and from 14
      individuals with impaired glucose tolerance (IGT) of 68 families, including 1
      family with maturity-onset diabetes of the young (MODY) and 3 families
      ascertained specifically for a mixture of NIDDM and IDDM. We tested 2 control
      populations: 50 unrelated spouses form Utah families, including 29 spouses with
      either IGT or NIDDM and 198 random nondiabetic white individuals from Colorado.
      RESULTS: We detected either GAD or ICA512 autoantibodies in 11 members of seven
      families and in one spouse used as a control subject. In two families, two
      affected individuals showed evidence of autoimmunity, but NIDDM individuals in
      each of the seven families showed no evidence of autoimmunity. Among the five
      families with both IDDM and NIDDM individuals (three families ascertained for a
      mixture and two families ascertained with an incidental IDDM child), antibodies
      were detected in members of only one family. Antibody-positive individuals were
      significantly younger at diabetes onset and had low waist-to-hip ratios, but were
      not more likely to be insulin treated. CONCLUSIONS: Autoimmunity is an important
      cause of apparent NIDDM, even among families with a strong history of NIDDM.
      However, autoimmunity among affected family members appeared to be a chance event
      and not the manifestation of a different genetic cause of diabetes.

PMID- 9250450
TI  - IDDM and milk consumption. A case-control study in Sao Paulo, Brazil.
AB  - OBJECTIVE: To test the hypothesis that breast-feeding is a protective factor
      against IDDM and that early exposure to cow's milk is a risk factor for the
      disease. RESEARCH DESIGN AND METHODS: A case-control study was conducted in Sao
      Paulo, Brazil. A total of 346 diabetic children, aged < 18 years, were identified
      in two institutions in the city of Sao Paulo. Duration of exclusive breast
      feeding and age of introduction to cow's milk products in infant diet were
      compared with 346 sex-, age-, and neighborhood-matched control children. All
      comparisons between diabetic and control children were done using paired tests.
      RESULTS: Statistically significant differences were found for the duration of
      exclusive breast-feeding (P = 0.007) and for the age of introduction to cow's
      milk products (P = 0.047). Control children had a longer time of exclusive breast
      feeding and had received cow's milk later in their diet than the case children.
      CONCLUSIONS: The results suggest that a shorter duration of exclusive breast
      feeding is a risk factor for IDDM (odds ratio [OR] 2.13; 95% CI 1.8-3.55) and
      that the introduction to cow's milk products before age 8 days is a risk factor
      for the disease.

PMID- 9250449
TI  - Proinsulin, intact insulin, and fibrinolytic variables and fibrinogen in healthy
      subjects. A population study.
AB  - OBJECTIVE: As high serum insulin predicts impaired fibrinolysis and proinsulin
      reacts in most conventional insulin assays, we hypothesized that proinsulin could
      link low fibrinolytic activity and hyperinsulinemic conditions. RESEARCH DESIGN
      AND METHODS: We explored the relationship between fibrinolysis and plasma
      fibrinogen on the one hand and specific insulin and proinsulin on the other, in a
      healthy population sample of 165 men and women, 25-74 years of age, from the
      Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular
      Disease) Study. Specific insulin and proinsulin were measured by enzyme-linked
      immunosorbent assay. Partial correlation coefficients, adjusted for age and sex,
      were calculated. RESULTS: Plasma fibrinogen levels were related to insulin (r =
      0.25, P < 0.01) and proinsulin (r = 0.29, P < 0.001), as was plasminogen
      activator inhibitor (PAI)-1 activity (r = 0.36 and r = 0.29, respectively; P <
      0.001). Tissue Plasminogen activator (tPA) activity correlated inversely to
      insulin (r = 0.35, P < 0.001) and proinsulin (r = - 0.36, P < 0.001). In a
      multivariate analysis taking also smoking and anthropometric and metabolic
      measurements into account, fasting proinsulin was a significant predictor of high
      plasma fibrinogen level. Insulin and proinsulin levels were not related to tPA
      activity. High levels of postload insulin, triglycerides, and diastolic blood
      pressure, but not proinsulin, predicted high PAI-l activity. CONCLUSIONS: In a
      healthy population, the relationship previously described between high insulin
      levels and impaired fibrinolysis is not attributable to confounding from
      proinsulin. Elevated proinsulin levels are associated with high fibrinogen
      levels.

PMID- 9250451
TI  - Determinants of growth in diabetic pubertal subjects.
AB  - OBJECTIVE: To analyze the relationship among metabolic control, IGF-I, and growth
      in pubertal diabetic subjects. RESEARCH DESIGN AND METHODS: In 72 diabetic
      children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF
      binding protein (BP)-1, and growth rate in different pubertal stages and have
      analyzed their relation to age sex, weight/length index, HbA1c, insulin
      concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS). RESULTS:
      The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased,
      whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values
      into SD scores, correcting for age, sex, and pubertal stage, it was shown that
      the deviation from normal values increased with increasing pubertal stage in
      boys, but was equal in stages 3-5 in girls. Using multiple regression analysis,
      HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score
      (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal
      range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in
      single correlation (r = -0.26, P = 0.02). In single correlation, growth rate
      correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple
      regression analysis, only DHEAS and IGF-I SD score were found to be significantly
      correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had
      reached their final height did not deviate from their target final height,
      according to their recorded growth since birth. CONCLUSIONS: In a group of fairly
      well-controlled diabetic children, the normal increase in IGF-I during puberty is
      blunted. Despite decreased IGF-I levels, target final height was attained,
      probably because of adequate insulin compensation leading to normal IGFBP-l, thus
      adequate bioavailability of IGF-I. Our results point out the importance of
      sufficient exogenous insulin in the period of rapid linear growth.

PMID- 9250452
TI  - Which features of smoking determine mortality risk in former cigarette smokers
      with diabetes? The World Health Organization Multinational Study Group.
AB  - OBJECTIVE: The effects of quitting smoking on mortality risk in individuals with
      diabetes is unknown and may differ from the benefits observed in the general
      population. We therefore determined the mortality risks in ex-smokers with
      diabetes, compared with subjects who have never smoked, by the number of years
      since quitting, the number of cigarettes smoked, and the number of years of
      smoking. RESEARCH DESIGN AND METHODS: An international cohort study of 4,427
      individuals with diabetes was studied. Baseline examinations were performed in
      1975-1977 when smoking habits were determined by questionnaire. Mortality follow
      up continued until 1988. RESULTS: All-cause mortality risks were higher for
      recent quitters (1-9 years; relative risk [RR], 1.53 [95% CI 1.19-1.97]; P =
      0.001) than for those who quit earlier (> or = 10 years; RR, 1.25 [95% CI 1.03
      1.52]; P = 0.02), compared with subjects who have never smoked. These risks were
      highest in those who had smoked the longest (> or = 30 years: RR, 1.66 [95% CI
      1.22-2.26]; P = 0.001; vs. 1-9 years: RR, 1.17 [95% CI 0.85-1.60]; P = 0.3).
      Risks were also highest in those who had smoked the most and least number of
      cigarettes. Adjustment for key confounders, which included a previous history of
      heart disease, proteinuria, and blood pressure, did not materially affect these
      relationships. CONCLUSIONS: Quitting smoking does reduce mortality risk in ex
      smokers with diabetes, but risks remain high several years after quitting and are
      highly dependent on the duration of smoking. Thus, individuals with diabetes who
      smoke should be encouraged to quit as soon as possible in the course of disease.

PMID- 9250453
TI  - Independent physiological predictors of foot lesions in patients with NIDDM.
AB  - OBJECTIVE: To identify and quantify independent physiological risk factors for
      foot lesions in diabetic patients. RESEARCH DESIGN AND METHODS: There were 352
      patients enrolled in a 1-year randomized controlled trial aimed at reducing risks
      for lower-extremity pathology through patient education and system interventions.
      Inclusion criteria were as follows: being age 40 years or over, being at or above
      ideal body weight, and having been diagnosed with NIDDM. Participants were
      predominantly African-American (76%), elderly (mean 60 years of age), indigent
      (77% with annual income < +10,000), or women (81%) who had diabetes for 10 years.
      Prospective multivariate modeling used baseline clinical signs (e.g., blood
      pressure, dermatological characteristics, and neuropathic measures) and
      laboratory values (e.g., lipid profiles and measures of glycemic control) to
      predict foot lesions rated using the Seattle Wound Classification. RESULTS: When
      controlling for intervention effects, only measures of neuropathy (monofilament
      testing [odds ratio ?OR? 2.75, 95% CI 1.55-4.88] and thermal sensitivity testing
      [2.18, 1.13-4.21]) predicted wounds classified 1.2 (minor injury), but
      investigation of wounds rated at least 1.3 (nonulcerated lesions) indicated
      baseline wounds (13.41), 3.19-56.26), monofilament abnormalities (5.23, 2.26
      12.13), and low HDL (1.63, 1.11-2.39) as predictors. Although fungal dermatitis,
      dry cracked skin, edema, ingrown nails, microalbuminuria, fasting blood glucose,
      and hemoglobin A1c were candidates for one or both of the multivariable models (P
      < 0.3), they were not significant multivariate predictors. CONCLUSIONS: Lesions
      may be preventable with aggressive screening for peripheral neuropathy and
      abnormal lipids. Also, these results provide empirical support for the commonly
      held belief that foot lesions prospectively predict future wounds.

PMID- 9250454
TI  - Metabolic efficacy of preprandial administration of Lys(B28), Pro(B29) human
      insulin analog in IDDM patients. A comparison with human regular insulin during a
      three-meal test period.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of the rapid
      acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently
      available short-acting human insulin in a multiple injection therapy (MIT)
      regimen with respect to blood glucose and plasma insulin profiles and to serum
      metabolites (lactate, free fatty acids, glycerol, and beta-hydroxybutyrate) in 12
      well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 +/- 0.9% [mean +/-
      SD]). RESEARCH DESIGN AND METHODS: After a run-in period of 4 weeks, patients
      were treated with either lispro at mealtime or human insulin 30 min before the
      meal for two periods of 4 weeks in a randomized open-label crossover study.
      Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of
      both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M.
      the next day. RESULTS: During the treatment periods, glycemic control was stable
      during lispro but improved during human insulin (delta HbA1c lispro 0.1 +/- 0.48,
      NS; human insulin -0.41 +/- 0.34%, P < 0.05). Glucose excursions, as measured by
      the incremental AUC, during the day and for the 2-h postprandial periods, were
      lower, although not significantly, for lispro. Insulin profiles demonstrated a
      faster rise after administration of lispro as compared with human insulin,
      peaking at 61 +/- 11.9 and 111 +/- 48.1 min (P < 0.01). Glycerol levels showed a
      slight increase before lunch and dinner, suggestive of enhanced lipolytic
      activity and compatible with the lower insulin levels. CONCLUSIONS: Lispro
      insulin applied in an MIT regimen creates more physiologic insulin profiles and
      tends to lower the glycemic excursions during the day compared with short-acting
      insulin. The analog can be applied safely in an MIT regimen, with mealtime
      intervals up to 5 h.

PMID- 9250455
TI  - Strategies toward improved control during insulin lispro therapy in IDDM.
      Importance of basal insulin.
AB  - OBJECTIVE: To examine whether overall glycemic control can be improved with
      insulin lispro by adjustment of the basal insulin regimen without an increased
      risk of hypoglycemia. RESEARCH DESIGN AND METHODS: A 5-month open study was
      performed in 66 IDDM patients after they had been transferred from human regular
      insulin to insulin lispro as a premeal therapy. The premeal and basal insulin
      regimens were adjusted according to self-monitoring of blood glucose during the
      visits at 2-week to 1-month intervals. Diurnal glucose profile, hypoglycemic
      events, HbA1c, and patient satisfaction were evaluated. RESULTS: The mean daily
      glucose level decreased from 9.2 +/- 0.2 to 8.4 +/- 0.2 mmol/l (P = 0.001) and
      HbA1c decreased from 8.8 +/- 0.1 to 8.0 +/- 0.1% (P < 0.001) (mean +/- SD). The
      number of daily NPH injections increased from 1.4 +/- 0.1 at baseline to 3.1 +/-
      0.1 at the end of the study. Total daily insulin dose increased by 3 U (7%)
      because of an 8-U (43%) rise in basal insulin, whereas premeal insulin dose
      decreased by 5 U (20%). The number of hypoglycemic episodes did not change during
      the study. Of the patients, 86% considered insulin lispro equal or better than
      human regular insulin. CONCLUSIONS: Although the study was open, the date suggest
      that the appropriate combination of insulin lispro and basal insulin can improve
      postmeal hyperglycemia, HbA1c, and treatment satisfaction without increasing the
      risk of hypoglycemia.

PMID- 9250456
TI  - Evaluation of the efficacy and tolerability of nitrendipine in reducing both
      pressure and left ventricular mass in hypertensive type 2 diabetic patients.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of nitrendipine in
      comparison with captopril in hypertensive diabetic patients with left ventricular
      hypertrophy (LVH). RESEARCH DESIGN AND METHODS: A total of 75 patients enrolled
      in this study presented stable type 2 diabetes (not treated with insulin) and
      mild-to-moderate hypertension with a left ventricular mass > or = 75 g/m2 by two
      dimensional echocardiography. After a 4-week washout period, 38 patients were
      assigned to treatment with captopril, and 37 patients to nitrendipine (random
      allocation). The duration of follow-up was 36 weeks. RESULTS: Patients of both
      groups were similar with regard to the duration of diabetes and hypertension,
      systolic and diastolic blood pressure at rest, degree of LVH, metabolic control,
      and albumin excretion rate (AER). Both drugs were equally effective in reducing
      systolic and diastolic blood pressure (captopril: from 165 +/- 13/100 +/- 4 to
      147 +/- 11/87 +/- 4 mmHg; nitrendipine: from 167 +/- 17/100 +/- 5 to 143 +/- 9/86
      +/- 4 mmHg; P < 0.05) and in reversing LVH (nitrendipine: from 87 +/- 2 to 81 +/-
      1 g/m2; captopril: from 89 +/- 2 to 85 +/- 2 g/m2; P = 0.0001). Neither the left
      ventricular end-diastolic volume index nor the left ventricular ejection fraction
      changed significantly during the treatment period. CONCLUSION: Nitrendipine is as
      effective as captopril in reducing both systolic and diastolic blood pressure and
      in reversing LVH. Neither drug showed any negative side effects on fasting plasma
      glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs.

PMID- 9250457
TI  - Preservation of physiological responses to hypoglycemia 2 days after antecedent
      hypoglycemia in patients with IDDM.
AB  - OBJECTIVE: To assess the effects of short-term antecedent hypoglycemia on
      responses to further hypoglycemia 2 days later in patients with IDDM. RESEARCH
      DESIGN AND METHODS: We studied eight type I diabetic patients without
      hypoglycemia unawareness or autonomic neuropathy during two periods at least 4
      weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU.m-2.min-1)
      hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced.
      Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps
      of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and
      physiological responses were measured every 10-20 min. RESULTS: When compared
      with the responses measured following euglycemia, the responses of norepinephrine
      2 days after hypoglycemia were reduced (peak, 1.4 +/- 0.4 [mean +/- SE] vs.1.0 +/
      0.3 nmol/l [P < 0.05]; threshold, 3.4 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l glucose [P
      < 0.01]). The responses of epinephrine (peak, 4.0 +/- 1.4 vs. 3.5 +/- 0.8 nmol/l
      [P = 0.84]; threshold, 3.8 +/- 0.1 vs. 3.6 +/- 0.1 mmol/l glucose [P = 0.38]),
      water loss (peak, 194 +/- 34 vs. 179 +/- 47 g-1.m-2.h-1 [P = 0.73]; threshold,
      2.9 +/- 0.2 vs. 2.9 +/- 0.2 mmol/l glucose [P = 0.90]), tremor (peak, 0.28 +/-
      0.05 vs. 0.37 +/- 0.06 root mean square volts (RMS V) [P = 0.19]; threshold, 3.2
      +/- 0.2 vs. 3.1 +/- 0.2 mmol/l glucose [P = 0.70]), total symptom scores (peak,
      10.6 +/- 2.1 vs. 10.8 +/- 1.9 [P = 0.95]; threshold, 3.3 +/- 0.2 vs. 3.6 +/0 0.1
      mmol/l glucose [P = 0.15]), and cognitive function (four-choice reaction time:
      threshold, 2.9 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l glucose [P = 0.69]) were
      unaffected. CONCLUSIONS: The effect on hypoglycemic physiological responses of 2
      h of experimental hypoglycemia lasts for 1-2 days in these patients with IDDM .
      The pathophysiological effect of antecedent hypoglycemia may be of shorter
      duration in IDDM patients, compared with nondiabetic subjects.

PMID- 9250458
TI  - Susceptibility to type 1 diabetes in the Senegalese population is linked to HLA
      DQ and not TAP and LMP genes.
AB  - OBJECTIVE: To investigate the frequency of the transporter associated with
      antigen processing (TAP) and large multifunctional protease (LMP) alleles and
      their role in the susceptibility to type 1 diabetes, in comparison with the well
      known HLA-DQ alleles susceptibility, in Senegalese subjects. RESEARCH DESIGN AND
      METHODS: Three loci in the TAP/LMP region were analyzed in 92 type 1 diabetic
      subjects and 117 nondiabetic control subjects by means of polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No
      association was found between the studied polymorphisms of TAP1, TAP2, and LMP2
      and type 1 diabetes in the Senegalese population, in contrast to the HLA-DQA1 and
      DQB1 genes, which were associated with type 1 diabetes. CONCLUSIONS: Diabetogenic
      genes in the class II HLA region are located near the DQA1 and DQB1 loci rather
      than the TAP and LMP loci.

PMID- 9250459
TI  - Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1
      activity in Pima Indians with type 2 diabetes.
AB  - OBJECTIVE: To examine the relationship between plasma plasminogen activator
      inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic
      retinopathy in Pima Indians with type 2 diabetes. RESEARCH DESIGN AND METHODS: We
      studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in
      a population-based epidemiological survey. Plasma PAI-1 activity was measured by
      a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase
      chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by
      ophthalmoscopy after pupillary dilation and classified as any retinopathy or as
      nonproliferative and proliferative. RESULTS: Retinopathy was present in 70 (41%)
      subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1
      activity was not significantly different among subjects with and without
      retinopathy (17.1 +/- vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1
      activity was negatively correlated with duration of diabetes (rs = -0.18, P =
      0.02). In a logistic regression analysis controlled for age, sex, BMI, and
      duration of diabetes, any retinopathy was significantly associated with fasting
      plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and
      HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of
      retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G,
      and 5G/5G were 44, 49, and 24%, respectively; chi 2 = 8.22, df = 2, P = 0.016)
      and remained significant after controlling for age, sex, BMI, duration of
      diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic
      regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and
      4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively.
      CONCLUSIONS: Although diabetic retinopathy in Pima Indians with type 2 diabetes
      is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype
      had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These
      preliminary findings indicate that in Pima Indians with type 2 diabetes, presence
      of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic
      retinopathy.

PMID- 9250460
TI  - Effect of race on outcome after kidney and kidney-pancreas transplantation in
      type 1 diabetic patients.
AB  - OBJECTIVE: The racial impact on graft outcome is not well defined in diabetic
      recipients. The purpose of this study is to analyze our experience with kidney
      alone (A) and kidney-pancreas (KP) transplantation in type 1 diabetic recipients
      and evaluate the impact of racial disparity on outcome. RESEARCH DESIGN AND
      METHODS: The records of 217 kidney transplants (118 KA, 99 KP) performed on type
      1 diabetic patients between 1985 and 1995 at the Medical University of South
      Carolina and the University of Texas Medical Branch were reviewed. RESULTS: A
      total of 53 (31%) white patients and 15 (33%) black patients experienced at least
      one episode of biopsy-proven acute rejection of the renal graft (NS). Patient
      survival at 1, 2, and 5 years was similar in white (92, 87, 69%) and black (91,
      91, 69%) patients (NS). Kidney graft survival at 1, 2, and 5 years in the KA
      group was 72, 62, and 42% in blacks, compared with 79, 76, and 53% in whites
      (NS). Kidney graft survival at 1, 2, and 5 years in the KP group was 92, 92, and
      74% in blacks, compared with 83, 77, and 58% in whites (NS). Pancreas graft
      survival at 1, 2, and 5 years was 81, 81, and 81% in blacks, compared with 81,
      75, and 62% in whites (NS). Cox regression analysis revealed that donor age > or
      = 40 years increased the risk of renal graft failure 6.2-fold (P = 0.0001),
      whereas the addition of a pancreas transplant to a kidney and a living-related
      transplant decreased the risk of failure of the kidney graft 0.2 (P = 0.005) and
      0.1 times (P = 0.005). CONCLUSIONS: Our results suggest that when compared with
      whites, there may be a trend toward an improved kidney and pancreas graft outcome
      in blacks undergoing KP transplants. These findings suggest that diabetes may
      override the risk factors that account for the pronounced disparity in outcome
      observed between nondiabetic white and black recipients.

PMID- 9250461
TI  - Determination of amputation level in ischemic limbs. Reappraisal of the
      measurement of TcPo2.
AB  - OBJECTIVE: To study the accuracy of the measurement of TcPo2 for the
      determination of the optimal level of amputation in patients with end-stage
      vascular disease (i.e., the level at which the reamputation rate and the
      proportion of too-proximal amputations will be minimized). RESEARCH DESIGN AND
      METHODS: We used a Medline literature search of all published studies of the past
      12 years that fulfilled predefined quality criteria, and we analyzed the data by
      means of receiver operating characteristic (ROC) curve. RESULTS: Ten studies
      could be identified with a total of 615 lower-limb amputations (51% of them being
      performed in diabetic patients) and a reamputation rate of 16.4%. The best
      performances of the TcPo2 measurement were obtained between 10 and 20 mmHg with
      an accuracy of approximately 80%. CONCLUSIONS: Preoperative TcPo2 measurement may
      be of considerable help to predict stump outcome and level of amputation. Our
      study provides objective prognostic values for the range 0-50 mmHg and suggests
      that TcP02 should usually be 20 mmHg at the site of amputation, which will
      predict healing with 80% accuracy and should, therefore, not be used as a sole
      criteron. Despite this aid in making his decision about the amputation level, the
      surgeon still has to balance between his goal of achieving primary wound healing
      and his hope of preserving the maximal limb length and has to consider patient
      preferences.

PMID- 9250462
TI  - The Trp64Arg polymorphism of the beta 3-Adrenergic receptor gene. Lack of
      association with NIDDM and features of insulin resistance syndrome.
AB  - OBJECTIVE: To investigate the association of the Trp64Arg polymorphism of the
      beta3-adrenergic receptor gene with NIDDM and the features of insulin resistance
      syndrome in subjects from eastern Finland. RESEARCH DESIGN AND METHODS: We
      determined the prevalence of the Trp64Arg polymorphism of the beta3-adrenergic
      receptor gene by restriction fragment length polymorphism analysis in 110
      patients with NIDDM (54 men and 56 women, age 63 +/- 1 years, BMI 30.4 +/- 0.5
      kg/m2), in 183 patients with features of insulin resistance syndrome (103 men and
      80 women, age 44 +/- 0 years, BMI 31.1 +/- 0.4 kb/m2), and in 82 normoglycemic
      control men (age 54 +/- 1 years, BMI 26.3 +/- 0.4 kg/m2). RESULTS: The allele
      frequency of the Trp64Arg polymorphism of the beta3-adrenergic receptor gene was
      similar in patients with NIDDM, in patients with insulin resistance syndrome, and
      in control subjects (0.08, 0.07, and 0.07, respectively; NS). In addition, this
      polymorphism was not associated with low resting metabolic rate, abdominal
      obesity, increased lipid oxidation, hypertension, or earlier development of NIDDM
      as previously described. Furthermore, in 82 normoglycemic male control subjects
      the Trp64Arg polymorphism was not associated with insulin resistance evaluated by
      the euglycemic-hyperinsulinemic clamp. CONCLUSIONS: The Trp64Arg polymorphism of
      the beta 3-adrenergic receptor gene is unlikely to be a major genetic predisposer
      to NIDDM or insulin resistance syndrome in subjects from eastern Finland.

PMID- 9250463
TI  - Evaluation of skin vasomotor reflexes in response to deep inspiration in diabetic
      patients by laser Doppler flowmetry. A new approach to the diagnosis of diabetic
      peripheral autonomic neuropathy.
AB  - OBJECTIVE: To evaluate the peripheral sympathetic function in feet of NIDDM
      patients by means of laser Doppler flowmetry. RESEARCH DESIGN AND METHODS: After
      deep inspiration, we measured the vasoconstrictor response in the feet of 51
      patients with NIDDM, as compared with those of 20 healthy control subjects, using
      laser Doppler flowmetry. Subjects whose skin temperature was < 32 degrees C were
      excluded from our study because a skin temperature of approximately 34 degrees C
      is the optimal temperature for the evaluation of skin vasomotor reflexes in
      response to a deep inspiration by laser Doppler flowmetry. RESULTS: The
      vasoconstrictor response to deep inspiration in the big toe was significantly
      decreased in NIDDM patients compared with healthy subjects (26.8 +/- 2.0 vs. 48.3
      +/- 18.5%, P < 0.0001). In NIDDM patients, the vasoconstrictor response was
      positively correlated with the duration of diabetes, the median motor and sensory
      nerve conduction velocities, the coefficient of variation of the R-R interval at
      rest, and the postural fall in systolic blood pressure. The vasoconstriction was
      inversely correlated with the vibratory perception threshold. CONCLUSIONS:
      Vasomotor reflexes in the lower limbs were markedly impaired in NIDDM patients.
      The measurement of vasoconstrictor responses to deep inspiration by using laser
      Doppler flowmetry is a novel and useful method for detecting peripheral
      sympathetic failure in diabetic patients.

PMID- 9250464
TI  - Glomerular hyperfiltration is associated with blood pressure abnormalities in
      normotensive normoalbuminuric IDDM patients.
AB  - OBJECTIVE: To analyze the blood pressure patterns in normoalbuminuric IDDM
      patients with glomerular hyperfiltration. RESEARCH DESIGN AND METHODS: A
      controlled cross-sectional study of 38 normotensive normoalbuminuric (urinary
      albumin excretion rate < 20 micrograms/min) IDDM patients (18 hyperfiltering
      [glomerular filtration rate > 134 ml.min-1 1.73 m-2] and 20 normofiltering) and
      20 normal individuals matched for age, sex, and BMI was performed. The 24-h
      ambulatory blood pressure was monitored using an auscultatory technique
      (Pressurometer IV, Del Mar Avionics), the glomerular filtration rate was measured
      by 51Cr-labeled EDTA method, extracellular volume by the distribution volume of
      51Cr-labeled EDTA, and the 24-h urinary albumin excretion rate by
      radioimmunoassay. RESULTS: Mean nocturnal diastolic blood pressure was higher in
      hyperfiltering IDDM patients (70.4 +/- mmHg), when compared with the control
      group (65.1 +/- 5.3 mmHg, P = 0.04). Diastolic blood pressure night:day ratio was
      higher in hyperfiltering IDDM patients (92.0 +/- 8.6%), when compared with
      normofiltering IDDM patients (85.9 +/- 4.8%) and control subjects (87.0 +/- 6.8%,
      P = 0.02). In IDDM patients, the glomerular filtration rate significantly
      correlated with the diastolic blood pressure night:day ratio (r = 0.5, P =
      0.002), extracellular volume (r = 0.04, P = 0.002), and HbA1 (r = 0.3, P = 0.03).
      In stepwise multiple regression analysis, factors associated with glomerular
      filtration rate were diastolic blood pressure night:day ratio, extracellular
      volume, and HbA1 (adjusted r2 = 0.27, P = 0.003). CONCLUSIONS: Glomerular
      hyperfiltration is associated with higher nocturnal diastolic blood pressure and
      with a blunted nocturnal decrease in diastolic blood pressure levels in
      normotensive and normoalbuminuric IDDM patients.

PMID- 9250465
TI  - The 32nd annual meeting of the European Association for the Study of Diabetes.
      Leptin, insulin resistance, intrauterine malnutrition, sulfonylureas, oral agents
      alone and with insulin, and new pharmacological approaches to type 2 diabetes.

PMID- 9250466
TI  - Oxidative stress and diabetic complications in young IDDM patients.

PMID- 9250467
TI  - Activated protein C resistance and Japanese NIDDM patients with coronary heart
      disease.

PMID- 9250468
TI  - Bone mineral density in diabetes.

PMID- 9250469
TI  - Is troglitazone a real indication for obese subjects with impaired glucose
      tolerance?

PMID- 9250470
TI  - Uremia and HbA1c.

PMID- 9250471
TI  - Evaluation of the acute behavioral effects and abuse potential of a C8-C9
      isoparaffin solvent.
AB  - We hypothesized that the abuse potential of certain types of inhalants could be
      evaluated in animals by determining the overlap in their profile of behavioral
      effects with that of CNS depressant drugs and other depressant-like abused
      inhalants. For our first attempt in evaluating a solvent with an unknown abuse
      potential we tested ISOPAR-E. ISOPAR-E is a mixture of predominantly C8-C9
      isoparaffinic hydrocarbons that is being used more and more frequently as a
      solvent in industrial and consumer products, including, but not limited to,
      typewriter correction fluids. Presently, nothing is known about the potential for
      abuse of products containing this solvent. In the present studies, we compared
      the volatility of ISOPAR-E and the abused solvent 1,1,1-trichloroethane (TCE) in
      our exposure systems. Additionally, five behavioral procedures were conducted in
      mice to compare the effects of the two compounds. The results demonstrate that:
      (1) ISOPAR-E was less volatile than TCE; (2) ISOPAR-E produced a somewhat
      different profile of effects than did TCE as assessed with a functional
      observational battery; (3) unlike TCE, ISOPAR-E did not affect performance on
      tests of motor coordination; (4) TCE and ISOPAR-E produced concentration-related
      decreases in schedule-controlled operant performance with recovery from TCE being
      somewhat more rapid; (5) ISOPAR-E produced cross dependence in TCE-dependent
      mice; and (6) both TCE and ISOPAR-E produced substantial levels of ethanol-lever
      responding in a drug discrimination procedure, although the ethanol-like effects
      of ISOPAR-E only occurred at response rate decreasing concentrations. Overall,
      there was a poorer separation of behavioral and lethal concentrations for ISOPAR
      E than for TCE. Although a somewhat different profile of behavioral effects was
      obtained with ISOPAR-E and TCE, we cannot say with certainty if enough
      similarities exist with abused inhalants to predict that ISOPAR-E would be
      subject to depressant-like abuse. Nonetheless, the feasibility of preclinical
      assessment of abuse potential of inhalants was demonstrated.

PMID- 9250472
TI  - Cigarette smoking and solvent use among Japanese adolescents.
AB  - To examine the relationship between cigarette smoking and solvent use among
      Japanese adolescents, epidemiologic data from a survey of 4433 junior high school
      students were analyzed. For both males and females, the frequency of cigarette
      smoking was positively associated with curiosity about solvent use, the
      perception of closeness to solvent users and the lifetime and past-year
      prevalence rates of solvent use. On the other hand, the frequency of smoking was
      negatively associated with the endorsement of the current Japanese law which
      maintains the illegality of solvent use. These results are reported for the first
      time from epidemiologic-based data among early adolescents in Japan. Although
      correlational, they suggest the role of cigarette smoking for Japanese
      adolescents in the initiation of other illicit drug use in these age groups.

PMID- 9250473
TI  - Tolerance development to morphine-induced alterations of immune status.
AB  - A variety of in vitro immune measures were examined in groups of Lewis rats that
      chronically consumed either tap water or a 0.2, 0.4, or 0.6 mg/ml morphine
      drinking solution. Rats received a subcutaneous injection of either saline or 15
      mg/kg morphine sulfate 1 h before sacrifice. In the drinking groups, the acute
      morphine injection significantly suppressed splenic natural killer (NK) cell
      activity, mitogen-stimulated splenic T- and B-cell proliferation and gamma
      interferon (gamma-IFN) production. A single, acute injection of morphine did not
      suppress NK cell activity in rats that drank the two highest concentrations of
      morphine, whereas it did suppress the mitogen-stimulated splenic T- and B-cell
      proliferation and gamma-IFN production. These results suggest that rats that
      drank morphine for 20 days developed tolerance to morphine's suppressive effect
      on NK cell activity but not to other measures of immune status. Morphine drinking
      rats also developed tolerance to morphine's antinociceptive effects and revealed
      signs of physical dependence when the morphine solution was withdrawn or when
      naltrexone was administered.

PMID- 9250474
TI  - Establishing preference for oral cocaine without an associative history with a
      reinforcer.
AB  - Using schedule-induced polydipsia (SIP), a stable, oral, preference for cocaine
      solution to water presented concurrently can be established by first presenting
      cocaine in a preferred vehicle, and subsequently fading the vehicle to water. The
      present study showed that rats exposed to a history of choosing 0.48 mg/ml
      cocaine in preference to concentrated lidocaine (2 mg/ml) under SIP conditions
      subsequently maintained this preference when the lidocaine concentration was
      progressively decreased to zero (water). Preference for lidocaine was tested by
      fixing it at 0.38 mg/ml (equimolar with 0.48 mg/ml cocaine) while subsequently
      increasing cocaine from 0.48 mg/ml to 2.5 mg/ml. Lidocaine preference did not
      occur, rather, preference for concentrated cocaine persisted. The results suggest
      that the avoidance of lidocaine solution may force the discrimination of the
      relation between high oral cocaine intake and its reinforcing effects, thereby
      instituting a stable preference for cocaine.

PMID- 9250475
TI  - Multi-level covariance structure analysis of intra-familial substance use.
AB  - Conventional covariance structure analysis, such as factor analysis, is often
      applied to data that are obtained in a hierarchical fashion, such as parents and
      siblings observed within families. However, multivariate modeling of such data
      are most frequently done as if the data were obtained as a simple random sample
      from a single population. An alternative specification is presented which
      explicitly models the within-level and between-level covariance matrices in
      familial substance use. Results demonstrate homogeneity in substance use within
      families but heterogeneity across families which could be accounted for by family
      level variables of marital status, economic status, and biological relationships.
      It is shown that conventional covariance structure software can be easily adapted
      to handle hierarchical models, providing a large set of new analysis
      possibilities for multi-level data.

PMID- 9250476
TI  - Effects of acute daily administration of diazepam on spatial learning and working
      memory.
AB  - This study evaluated the acute or daily effects of diazepam (DZP) on the
      acquisition and performance of rats in an 8-arm radial maze. Male Wistar rats
      (200-250 g) were divided into three groups: saline-saline (SS), saline-DZP (SD)
      and DZP-DZP (DD). The SS group always received intraperitoneal (i.p.) saline
      (SAL) in daily or acute treatments. The SD group received SAL (i.p.) daily during
      the task acquisition (30 days), DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s
      and 1 h delay tests, and it also received DZP (10 mg/kg, i.p.) for 70 days. The
      DD group received DZP (10 mg/kg, i.p.) daily during 30 days in the task
      acquisition, DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay
      tests and further received DZP (10 mg/kg, i.p.) for an additional 70 days. Our
      results showed that as compared to control (SS group), 8-10 h prior
      administration of a single daily dose of DZP (10 mg/kg) did not alter the
      learning and the performance of short- (5 s delay) and long-term (1 h delay)
      working memory. However, the acute administration of DZP (2.5 mg/kg) impaired the
      performance of the short delay task (5 s delay) in animals previously exposed (DD
      group) or not (SD group) to daily DZP treatment. Therefore, the acute
      administration of an anxiolytic dose of DZP (2.5 mg/kg) produced a significant
      impairment of short-term working memory, even in animals exposed to daily DZP
      treatment for a long time.

PMID- 9250477
TI  - Development of genetically engineered mice with hypertension and hypotension.
AB  - Human essential hypertension is generally recognized as a multifactorial disease
      involving the interplay of environmental factors based on genetic diathesis.
      Spontaneously hypertensive rats (SHR) and Dahl rats are widely used as animal
      models for human essential hypertension and salt-sensitive hypertension,
      respectively. The definitive genetic factor ruling the development of
      hypertension in these strains remains unclear, but recently advances in embryonic
      engineering and molecular biological techniques may make it possible for
      transgenic mice and gene-targeted mice to become important pathological models
      defined genetically and functionally for human disease. The author developed two
      types of genetically engineered mice that may serve as such models: a transgenic
      mouse with hypertension caused by enhancing the renin-angiotensin system and a
      gene-targeted mouse with hypotension caused by disrupting the renin-angiotensin
      system.

PMID- 9250478
TI  - Superovulation induction in the house musk shrew (Suncus murinus).
AB  - The number of ovulated oocytes in the adult house musk shrews was examined by
      natural mating. The positive rate of ovulation was 83.3%, and the mean number of
      ovulated oocytes was 4.4 +/- 1.9 (Mean +/- SD). The induction of superovulation
      was examined by administering either pregnant mare's serum gonadotropin (PMSG) or
      human chorionic gonadotropin (hCG), exogenous gonadotropin, to house musk shrews.
      As a result, the number of ovulated oocytes were within the number of oocytes
      ovulated spontaneously. The method of superovulation induction by administering
      both PMSG and hCG to house musk shrews was investigated. In the group
      intraperitoneally with 7.5 i.u. of PMSG followed by 7.5 i.u. of hCG 48 hr later,
      the positive rate of ovulation was as high as 94.6% and the mean number of
      ovulated oocytes was 11.7 +/- 13.4. Moreover, in 15 out of these 35 animals
      positive for ovulation, 10 oocytes or more were observed and the mean number of
      ovulated oocytes was 21.0 +/- 16.5, showing the superovulatory response. In the
      group of 5.0 i.u. PMSG and 5.0 i.u. hCG injected at an interval of 72 hr, every
      animal was induced to ovulate and the mean number of ovulated oocytes was 41.3 +/
      19.9. Thus, the injection of PMSG and hCG at a longer interval increased the
      number of superovulated oocytes. Furthermore, 97.5% of eggs recovered from
      superovulating animals contained cumulus cells.

PMID- 9250479
TI  - Morphological changes in hepatic Ito cells after parenteral treatment with
      carmellose sodium in rats.
AB  - Carmellose sodium (1.5%), dissolved in physiological saline, was given for 4 days
      via oral, subcutaneous or intraperitoneal routes. In the rats treated with
      carmellose sodium by the parenteral route, hepatic sinusoidal component cells and
      free macrophages were swollen. The degree of the swelling was more severe in the
      rats treated by the intraperitoneal route than by the subcutaneous route. The
      swollen sinusoidal component cells which engulfed the carmellose sodium-related
      substance were classified as Kupffer's cells or Ito cells by immunohistochemical
      reaction. Ito cells were isolated from a 5-week-old rat and were cultured in
      Dulbecco's modified Eagle's medium (DMEM). Some of the Ito cells which were
      cultured in DMEM containing 0.3% carmellose sodium showed phagocytic properties;
      vesicles in their cytoplasm and other Ito cells which were cultured in DMEM
      containing India ink contained some carbon particles.

PMID- 9250480
TI  - 125I uptake competing with iodine absorption by the thyroid gland following
      povidone-iodine skin application.
AB  - Povidone-iodine solution is widely used to disinfect the skin surface or prevent
      suppuration during human and animal surgery. Using radioisotope 125I, we examined
      whether iodine may be absorbed and then concentrated in the thyroid gland when
      povidone-iodine solution is applied to the skin of rats or mice. The competition
      for 125I uptake was examined in mice and rats after the application of povidone
      iodine to the skin. We also traced the process of absorbed 125I in the thyroid
      glad during the fixation for tissue preparations. Povidone-iodine applied to the
      skin significantly reduced the uptake of 125I both in mice and rats. Significant
      flux of 125I from the thyroid gland in povidone-iodine treated animals was noted
      during the thyroid fixation of tissue preparations. From these results, povidone
      iodine application to the skin instead of stable KI administration may be
      practical for preventing the uptake of 125I by the thyroid gland during 125I
      compound administration for medical therapy. In animal experiments concerning
      thyroid functions, careful attention must be paid when povidone-iodine is used
      for disinfection in animal surgery.

PMID- 9250481
TI  - Immunohistochemical study on galactosamine-induced subacute hepatitis in rats of
      JCL: Wistar-TGN (ARGHGEN) 1 Nts strain (Mini rats).
AB  - Immunohistochemical study was carried out on D-galactosamine hydrochloride (GaIN)
      induced subacute hepatitis in rats of JCL: Wistar-TGN (ARGHGEN) 1Nts strain (Mini
      rats), in which the expression of growth hormone gene is suppressed by the
      presence of an antisense transgene. Mini rats were given 1000 mg/kg of GaIN once
      a week for 4 consecutive weeks and killed at 1, 2, 3 and 4 weeks after the first
      administration. At 1 week after the first administration, proliferation of small
      epithelial cells positive for both alpha-fetoprotein and cytokeratin 7, i.e. so
      called oval cells, was observed in the whole area of each hepatic lobule, and
      prominent deposition of fibronectin, laminin and type IV collagen was detected
      around these oval cells. Together with these extracellular matrix components,
      many activated Ito cells positive for both desmin and alpha-smooth muscle actin
      were observed. With time, most of the oval cells formed duct-like structures and
      lost their positive stainability for alpha-fetoprotein, and many Ito cells became
      inactive. Deposition of fibronectin decreased rapidly from 2 weeks after the
      first administration. At 4 weeks after the first administration, deposition of
      laminin was detected only around the duct-like structures, where that of type IV
      collagen was also still prominent. These results suggest that a large population
      of oval cells differentiated into bile duct epithelial cells and that Ito cells
      and extracellular matrix components might play a role in this process.

PMID- 9250482
TI  - Age-related changes in susceptibility of mice to low-virulent mouse hepatitis
      virus (MHV-2-CC) infection.
AB  - This study was performed to examine mouse age-dependent changes in susceptibility
      to MHV-2-CC-infection and participation of macrophages in such changes in BALB/c
      mice. One-week-old mice were fully susceptible (mortality, 100%), 2-week-old semi
      susceptible (36%), and 3- and 4-week-old fully resistant (0%) to MHV-2-CC,
      respectively. Such age-dependent differences corresponded well with the
      differences in the virus titers in the liver, spleen and blood and in the
      severity of liver lesions. In 1-week-old mice with peritoneal exudate cells (PEC)
      transferred from 4-week-old mice and infected with MHV-2-CC, a slight
      prolongation of survival time was recorded, although there was no difference in
      mortality. In 3-week-old mice infected with MHV-2-CC after silica-treatment to
      suppress macrophages, there was no significant change in susceptibility. In
      macrophages infected with MHV-2-CC in vitro, the virus replicated better in
      macrophages obtained from younger mice. These results suggest that macrophages
      may play a small role in the age-related development of resistance to MHV-2-CC
      infection in BALB/c mice.

PMID- 9250483
TI  - Protective effects of a novel quinone derivative, E3330, on mouse hepatitis virus
      (MHV)-induced chronic hepatitis in athymic nude mice.
AB  - In this experiment, we examined the protective effects of a novel quinone
      derivative, E3330, on MHV-2cc-induced chronic hepatitis in athymic nude mice for
      up to 3 weeks after virus infection. The daily dose of 25 mg/kg b.w. suppressed
      the viral replication in the liver and the progression of hepatic lesions. The
      expansion of small focal lesions at 1 week after viral inoculation (WAI) was
      suppressed at 2 WAI, and the lesions were still small at 3 WAI in E3330
      administered group, whereas small focal lesions at 1 WAI were expanded at 2 WAI
      to fuse with each other at 3 WAI in the control group. E3330 therefore showed
      protective effects on MHV-2cc-induced chronic hepatitis in athymic nude mice, but
      further studies are needed to analyze the mechanism.

PMID- 9250484
TI  - Naturally occurring dermatitis associated with Staphylococcus aureus in DS-Nh
      mice.
AB  - A naturally occurring epizootic of dermatitis involved all the mice,
      provisionally designated as DS-Nh, housed under conventional conditions,
      regardless of age or sex. The disease primarily attacked the lateral aspect of
      the face, neck and shoulders. The histopathologic features of the dermatitis
      varied in severity, but all affected regions showed signs of chronic dermatitis,
      including infiltration of inflammatory cells, parakeratosis and amyloidosis, and
      contained Gram-positive cocci clusters. Bacteriologically, coagulase-positive
      Staphylococcus aureus (S. aureus) was recovered in pure culture from the skin
      lesions. The disease experimentally induced with the S. aureus isolates was
      indistinguishable from those observed in naturally occurring cases. The results
      suggested that S. aureus may be casually associated with the disease.

PMID- 9250485
TI  - Simple and efficient vitrification procedure for cryopreservation of mouse
      embryos.
AB  - Mouse pronuclear oocytes and 2-cell embryos derived from in vitro fertilization
      were cryopreserved by a novel simple vitrification procedure. Most cryopreserved
      oocytes/embryos were morphologically normal after warming, and 89-92% of them
      developed to the blastocyst stage during the culture. Moreover, the rate of
      morphologically normal pronuclear oocytes after being repeatedly cooled and
      warmed three times was as high as that of oocytes cooled and warmed only once,
      and 85% of them developed to the blastocyst stage. In addition, 43-57% of the
      cryopreserved oocytes/embryos transferred to recipients had developed normally to
      live fetuses observed on day 18.5 of pregnancy.

PMID- 9250486
TI  - TM rats: a model for platelet storage pool deficiency.
AB  - TM rats have a light brown hooded coat pattern resembling that of Fawn hooded
      (FH) rats which are a model of platelet storage pool deficiency (SPD). We
      examined whether the TM strain has the same platelet SPD as the FH strain. TM
      rats had a prolonged bleeding time and a low blood serotonin level, although
      their blood coagulation time and platelet counts were normal. The light coat
      color of the TM strain was judged to be associated with the red-eyed dilution
      gene as in the FH strain, but not pink eye dilution as in the RCS rat strain.
      Platelet SPD seen in TM rats may be a pleiotropic effect of the red-eyed dilution
      gene proposed in FH rats. Despite these similarities, the genetic background of
      the TM strain was obviously different from that of the FH strain. The TM strain,
      developed independently of the FH strain, will therefore be used as a model of
      platelet SPD.

PMID- 9250487
TI  - Pneumocystis carinii cysts are susceptible to inactivation by chemical
      disinfectants.
AB  - The inactivation efficacy of eight disinfectants commonly used in laboratories
      and animal rooms to inactive Pneumocystis carinii cysts was estimated by
      experimental infection in C.B-17-scid mice. The disinfectants examined in this
      study were 70% ethyl alcohol, 10% iodoform, 0.5% hypochlorous acid, two 1%
      quanternary ammonium salts, 3% hydrogen peroxide, sodium chlorite and 1% cresol
      soap. The lung homogenates from P. carinii infected C.B-17-scid mice were treated
      with each disinfectant for 15 min at room temperature, washed with saline, and
      inoculated into C.B-17-scid mice. Eight weeks after inoculation, lungs from these
      mice were examined by staining with toluidine blue O to detect P. carinii cysts.
      PCR amplifying 346 bp of P. carinii specific mitochondrial ribosomal RNA large
      segments was also performed using DNA extracted from the lungs of the mice. As a
      result, seven disinfectants, excepting for 0.5% hypochlorous acid, were effective
      in the inactivation of P. carinii cysts. These results suggest that P. carinii
      cysts were sensitive to chemical disinfectants even though they have been
      commonly considered as insensitive.

PMID- 9250488
TI  - No effect of voluntary exercise on ovarian follicle in rats.
AB  - The present study was to clarify the relationship between voluntary exercise and
      follicular growth or ovulation. Rats kept for 4 weeks in a rotating drum with
      free access to the wheel, food and water ran 2-12 km per day. The number of ova
      shed after superovulation treatments and the number of non-atretic follicles were
      not influenced by voluntary exercise. These experiments demonstrate that
      spontaneous voluntary exercise does not affect either the number of ova shed or
      the number of non-atretic follicles in superovulating rats or control rats.

PMID- 9250489
TI  - [Incidence of postmicturition dribble in adult males in their twenties through
      fifties].
AB  - A survey was conducted to investigate postmicturition dribble in the general
      adult male population. A questionnaire was sent to 3,034 clerical workers between
      20 and 50 years of age living in urban areas of Hokkaido and Tokyo, and it was
      returned by 2,839 men (93.5). The incidence of postmicturition dribble in the men
      in their 20s, 30s, 40s and 50s, was 11.5, 13.2, 19.4 and 26.9%, respectively. The
      overall incidence was 17.1%. Of those who had experienced postmicturition
      dribble; 14.0% dribbled almost daily but the degree of postmicturition dribble
      was limited to spotting or wetting of the underwear in 93.2%. Therefore, 2.3% of
      all respondents answered that they had experienced postmicturition dribble almost
      daily. It is concluded that postmicturition dribble is fairly common in adult
      men.

PMID- 9250490
TI  - [Usefulness of recombinant human erythropoietin on predeposit autologous blood
      transfusion in patients undergoing radical prostatectomy].
AB  - The usefulness of recombinant human erythropoietin (rHuEPO) on autologous blood
      transfusion was investigated in 18 patients undergoing radical prostatectomy
      (mean age 67.4 years). A total of 800 ml blood was deposited by two donations of
      400 ml each, concomitant with subcutaneous administration of 24,000 U rHuEPO at
      each donation. All patients completed two successive donations with no adverse
      effects. The mean hemoglobin concentration was 13.7 g/dl before the donation and
      13.0 g/dl on the day of operation. The decrease in hemoglobin was effectively
      prevented in 12 patients (66.7%) with rHuEPO, when compared with the predicted
      decrease in the absence of recovery from anemia. During radical prostatectomy, no
      homologous blood transfusion was required in 16 of 18 patients (88.9%). In
      conclusion, predeposit autologous blood transfusion with rHuEPO is useful for
      diminishing the risks associated with homologous blood transfusions.

PMID- 9250491
TI  - [Transurethral balloon laser thermotherapy for benign prostatic hyperplasia].
AB  - Between April 1994 and March 1995, transurethral balloon laser thermotherapy
      (TUBAL-T) using Prostalase was performed on 53 patients with benign prostatic
      hyperplasia. Clinical efficacy was evaluated at 3 months after TUBAL-T. The mean
      international prostate symptom score (I-PSS) decreased from 21.5 at baseline to
      11.3 after 3 months (p < 0.0001). Irritative (the sum of items 1, 2, 4 and 7 of I
      PSS) decreased by 55%, while obstructive symptoms (the sum of items 3, 5 and 6 of
      I-PSS) by 45%. However, other objective parameters such as maximum flow rate,
      voided volume, percent postvoid residual volume and prostate volume showed no
      significant change (7.8 to 7.2 ml/s, 130 to 147 ml, 33 to 28% and 39.7 to 41.0
      ml, respectively). In conclusion, significant improvement after TUBAL-T was
      observed for subjective symptoms, especially irritative symptoms, but not for
      objective parameters.

PMID- 9250492
TI  - [Luteinizing hormone-releasing hormone for prostate cancer in a hemodialysis
      patient: a case report].
AB  - An 81-year-old man on chronic hemodialysis was referred to our hospital with
      urinary difficulty. Transperineal needle biopsy of a hard nodule in the prostate
      revealed moderately differentiated adenocarcinoma. He was diagnosed to have stage
      C prostate cancer. A standard dose of luteinizing hormone-releasing hormone (LH
      RH) analogue, leuprorelin acetate (3.75 mg), was administered every 4 weeks for
      15 months. No adverse effects were observed throughout the period. The clinical
      response to LH-RH analogue was excellent, with normalization of serum prostate
      specific antigen level and relief of dysuria. Thus the standard dosage of LH-RH
      analogue is considered to be adequate for hemodialysis patients.

PMID- 9250493
TI  - [Mitrofanoff procedure with bladder-sparing urethrectomy in female urethral
      carcinoma: report of a case].
AB  - A 60-year-old woman with urethral carcinoma treated by bladder sparing surgery is
      reported. A tumor of Grabstald's clinical stage C2 arose from the anterior
      urethra infiltrated into the distal wall of vagina with invasion of vaginal
      mucosa. Pathological findings revealed poorly differentiated squamous cell
      carcinoma. She underwent a wide local excision of the urethra and the anterior
      vaginal wall with preserving the bladder. An appendicovesicostomy (Mitrofanoff
      procedure was selected for the urinary diversion. This technique provided a small
      stoma, appropriate continence, normal bladder sensation and preseving renal
      function. Bladder-sparing urethrectomy could be an alternative treatment for
      female urethral tumors.

PMID- 9250494
TI  - [Metastatic tumor of spermatic cord and tunica vaginalis testis from gastric
      cancer: a case report].
AB  - A 62-year-old man with advanced gastric cancer was admitted with a swelling of
      the left scrotum. He had undergone subtotal and total gastrectomies 10 and 5
      years earlier, respectively. A hard mass was palpated along the left spermatic
      cord associated with hydrocele testis. A left high orhiectomy was performed.
      Multiple small nodules were noted on the surface of the tunica vaginalis. Also, a
      tumor in the spermatic cord was present at the level of the internal inguinal
      ring, protruding into the peritoneal cavity and adherent to the colon.
      Peritonitis carcinomatosa was recognized. Histopathological diagnosis was tubular
      adenocarcinoma showing extensive vascular invasion, consistent with a metastasis
      from gastric cancer.

PMID- 9250495
TI  - [A case of 47XYY syndrome presenting with male infertility].
AB  - A 32-year-old man was referred to our hospital for primary infertility of a 4.5
      year duration. Neither character nor intelligence disorders were observed.
      Bilateral testes measured 16 ml each. Sperm density was 0-0.1 x 10(6)/ml on 3
      separate occasions. Endocrine examinations were all within normal limits.
      Maturation arrest was found on testicular biopsy. Karyotyping showed 47, XYY
      inversion. Polymerase chain reaction revealed no deletion of the azoospermic
      factor (AZF) gene on the Y chromosome. This is the 6th case reported in the
      Japanese literature of the 47XYY syndrome presenting with male infertility.

PMID- 9250496
TI  - [Clinical statistics of living and cadaveric renal transplantation at the
      Department of Urology, Mie University School of Medicine].
AB  - A statistic survey was made on the clinical results of living and cadaveric renal
      transplantations performed at our department between October 1980 and June 1996.
      A total of 38 patients received 6 living and 32 cadaveric renal transplants. The
      graft and patient survival rates of a living renal transplantation were 83.3% and
      100% at 3 years, respectively. The graft survival rate of cadaveric renal
      transplantation was 66.3% at 3 years and 56.0% at 5 years. In a cadaveric renal
      transplantation, patients with episodes of acute rejection within 12 months
      showed a significantly worse graft survival rate. This clinical parameter seems
      to be a prognostic factor for a long-term graft survival.

PMID- 9250498
TI  - [Diagnosis and follow-up of prostate cancer patients using prostate specific
      antigen (PSA)].
AB  - An international standard of prostate specific antigen (PSA) assays was
      constructed and prognosis of the patients with prostate cancers showing gray zone
      PSA was studied. For lower levels of serum PSA (< 50 ng/ml), the conversion
      formula to that of Tandem-R PSA from other assays was presented. Furthermore,
      based on the standards of Stanford Reference and Markit-MPA, conversion rates to
      this international standard from the conventional PSA assays were also obtained.
      Patients' cancer-specific survival was found to be significantly better in the
      gray zone group. Further studies to obtain higher specificity such as using free
      or complex rate in total PSA is necessary.

PMID- 9250497
TI  - [Mass screening for prostatic cancer].
AB  - Two mass screening programs for prostatic cancer (PC) have been conducted at our
      institution. The first program, based on transrectal ultrasonography (TRUS), was
      performed between 1975 and 1995 in a total of 16,313 men over 55 years of age.
      Those showing abnormal findings on TRUS were referred to the secondary urological
      examination including needle biopsy of the prostate. PC was detected in 93 men
      (0.6%) and 43 of them were in the early stage. In 1995, a new mass screening
      program for PC was performed in an urban area of Kyoto. Of 3,749 men over 55
      years of age who took the annual health checkup organized by the government,
      2,387 wished to receive this screening. The primary examination consisted of
      Delfia prostate specific antigen (PSA) assay of dried blood samples on a filter
      paper. Men with PSA levels > 4.0 and < or = 10.0 ng/ml showing abnormal findings
      on TRUS and/or digital rectal examination, or PSA density > 0.15, underwent 6
      sextant biopsies under transrectal ultrasonography, as well as men with PSA
      levels > 10.0 ng/ml. PSA levels were < or = 4.0 in 2,217 men, > 4.0 and < or =
      10.0 in 107, and > 10.0 in 43. Prostatic biopsy was performed in 102 men. PC was
      detected in 28 men (1.2%) and 17 of them were in the early stage. These findings
      suggest that the PSA-based mass screening program for PC combined with the annual
      health checkup is suitable for future "national-level" screening.

PMID- 9250499
TI  - [Clinical outcome of radical prostatectomy for stage C prostate cancer:
      comparison with other treatment modalities].
AB  - Of the 69 patients with clinical stage C prostate cancer under 75 years old and
      with good performance status between 1986 and 1995, 29 underwent radical
      prostatectomy combined with endocrine therapy, 21 underwent radiation therapy
      combined with endocrine therapy and remaining 19 patients were treated by
      endocrine therapy alone. The median followup was 44 months (range 4 to 122).
      Radical prostatectomy resulted in progression-free rates of 79% and 61% at 5 and
      10 years, respectively. Progression-free rates were lower in patients with lymph
      node metastasis or positive surgical margins. In patients with clinical stage T3a
      c and well or moderately differentiated tumor, radical prostatectomy resulted in
      a progression-free rate of 100% at 5 years. However, in patients with clinical
      stage T4a or poorly differentiated tumor, radiation therapy resulted in a better
      progression-free rate than radical prostatectomy. These findings suggest that
      patients with clinical stage T3a-c and well or moderately differentiated tumor
      will benefit from radical prostatectomy combined with endocrine therapy and that
      radiation therapy well be effective for advanced diseases.

PMID- 9250500
TI  - [Treatment of prostate cancer by radiotherapy].
AB  - Fifty-seven patients with clinically localized prostate cancer were treated by
      radical prostatectomy or external radiation therapy following pelvic
      lymphadenectomy. Comparing the outcome of radiotherapy with that of prostatectomy
      in 42 T2 patients without lymph node metastasis, the 5-year cause-specific
      survival did not differ between the radical prostatectomy group (n = 31) and
      radiotherapy group (n = 11). The 5-year disease-free survival of the
      prostatectomy group, however, was superior to that of radiotherapy group (p =
      0.01). To cure patients with T2 prostate cancer, therefore, it is supposed that
      radical prostatectomy should be performed. To improve the treatment outcome after
      radiotherapy, stereotactic radiosurgery for prostate cancer has been attempted in
      our institution. Phantom experiments using a linear accelerator demonstrated a
      round dose distribution, and high reproducibility of prostate positioning was
      confirmed by CT when a thermoplastic immobilization device was used to fix the
      pelvis. In one patient with localized prostate cancer treated by radiosurgery,
      acute complication has not been recognized during the 5 week follow-up.
      Radiosurgery may be available to treat clinically localized prostate cancer.

PMID- 9250501
TI  - William Earl Petersen, 1892-1971: a brief biography.

PMID- 9250502
TI  - Reducing milk production in ewes at weaning using restricted feeding and
      methscopolamine bromide.
AB  - Restricted feed (RF) and methscopolamine bromide (MB), an anticholinergic agent
      reported to block growth hormone secretion, were evaluated as potential means for
      reducing milk production in ewes at weaning. On d 58 +/- 1 postpartum (d 0), 40
      fall-lambing ewes were allotted to treatments in a 2 (RF vs full feed [FF]) x 2
      (MB vs saline [SAL]) factorial arrangement according to breed, age, and number of
      lambs born and suckled. On d 0 at 0800, ewes were separated from lambs, injected
      with 40 IU of oxytocin, and machine milked 30 s later. Ewes remained separated
      from lambs for 3 h, and at 1100 they were milked and yields were determined. From
      d 0 through 6, FF ewes received a daily ration of 1.8 kg of alfalfa hay and .9 kg
      of corn; RF ewes received only 1.8 kg of alfalfa hay. On d 7 at 0800 and 1400,
      ewes were separated from lambs, milked, treated with a s.c. injection of either
      96 mg of MB dissolved in 2 mL of SA or SA alone, and after 3-h separations were
      milked at 1100 and 1700 and yields determined. Lambs were weaned at 1400. After
      milking at 1700, all ewes were placed in drylot without feed or water. At 1100 on
      d 9, residual milk yields were collected. Milk samples were retained for
      compositional analysis at each collection time. The RF ewes produced less milk
      than FF ewes (106 vs 137.4 g; P < .01) at 1100 on d 7, but yields of MB and SA
      ewes were similar. At 1700 on d 7, milk yield was only 15.9 g less (74.3 vs 90.2
      g; P < .10) for RF than for FF ewes, but it was 26 g less (69.2 vs 95.2 g; P <
      .01) for MB than for SA ewes. On d 9, there was no significant difference in
      yields of RF and FF ewes; however, MB ewes continued to produce less milk than SA
      ewes (96.6 vs 125.4 g; P < .10). No significant interactions between feeding
      regimen and MB treatment were found for milk yield. These data provide evidence
      that MB treatment of ewes is effective in reducing milk production. Furthermore,
      even greater reduction can be achieved when MB is combined with RF.

PMID- 9250503
TI  - Feed intake pattern of group-housed growing-finishing pigs monitored using a
      computerized feed intake recording system.
AB  - The feed intake pattern and growth performance of boars, barrows, and gilts fed
      diets differing in lysine and protein content were measured on 120 crossbred pigs
      from 27 (SD 3.7) to 81.5 (SD 9.2) kg live weight. The pigs were housed in eight
      mixed-sex groups with five pigs of each sex in each group. They were fed from an
      electronic feed station that recorded individual meal sizes and the time and
      duration of visits to the feeder for each animal in the group. Four dietary
      treatments were compared. During the grower period (27 to 55 kg), diets ranged in
      lysine content form .98 to 1.31%; for the remainder of the study, lysine content
      was .88 to 1.18%. Barrows had a greater (P < .01) number of meals per day than
      the other two sexes (7.4 vs 7.0 vs 7.0 +/- .10, respectively), but there were no
      significant differences among sexes for daily feed intake or other feed intake
      traits. Daily feed intake increased with dietary lysine content, largely because
      of increased meal sizes resulting from longer feeder occupation times at each
      visit. Visits to the feeder were greatest between 0900 and 1100 and lowest
      between 2000 and 0400. Correlations between feeding pattern and growth traits
      were relatively low. Repeatabilities of feeding pattern traits were generally
      higher when measured over shorter time periods. These results suggest a change in
      feeding behavior with increasing dietary lysine levels and a relatively small
      effect of sex on feeding pattern for mixed-sex groups of 15 pigs fed from a
      single electronic feed station.

PMID- 9250504
TI  - Effects of sire, dam traits, calf traits, and environment on dystocia and
      subsequent reproduction of two-year-old heifers.
AB  - A study was conducted over 3 yr to evaluate effects of sire birth weight EPD,
      calf birth weight and shape, and heifer pelvic area and weight, individually and
      in combination, on dystocia and subsequent rebreeding of 2-yr-old heifers.
      Heifers (n = 550), MARC II yearlings, were assigned for breeding to one of four
      Angus sires with birth weight EPD of -.95, -82, +2.9, and +2.7 kg. At calving,
      heifers were assisted as needed. A gauge attached to the cal puller recorded
      applied traction pressure. Analysis of traction pressure detected only slightly
      larger amounts of variation (2 to 3%) affecting dystocia than the standard five
      point scoring system. Dam weight did not affect calving difficulty score (CDS),
      except dam birth weights were heavier (P < .05) for CDS 5 (Caesarean section)
      than CDS 1 (unassisted). Dams requiring Caesarean section had smaller pelvic
      areas (P < .05), with no other differences among CDS. The CDS increased as calf
      birth weight and cal external measurements increased. Low EPD sires produced
      calves with smaller (P < .05) birth weights and smaller calf head and food
      circumferences and caused less dystocia than high EPD sires. The CDS did not
      affect subsequent pregnancy rates but did affect conception date of the second
      calf. Calves delivered by Caesarean section were lighter (P < .05) at weaning
      than other calves but had similar slaughter weights. As mean winter temperature
      increased (6.1 degrees C) from yr 1 to 3, calf birth weight decreased (4.6 kg)
      and calving difficulty decreased 23%. Results indicate sire birth weight EPD,
      calf birth weight and shape, dam pelvic area, and climate affected CDS, and CDS
      affected subsequent conception date.

PMID- 9250505
TI  - Divergent selection for heat loss in mice: I. Selection applied and direct
      response through fifteen generations.
AB  - Divergent selection for heat production/loss (kcal.kg-.75.d-1), measured in 9- to
      11-wk-old male mice, was conducted for 15 generations. Heat loss was measured for
      15 h on individual animals placed overnight in direct, gradient-layer
      calorimeters. Selection for high (MH) and low (ML) heat loss and unselected
      control (MC) occurred in each of three replicates for a total of nine unique
      lines. Repeatability of the heat loss measurement was .45 and the CV was 10.5%.
      Cumulative realized selection differentials, averaged for the three replicates,
      were 145.1 and -105.0 (kcal.kg-.75.d-1) and ranged from 136.9 to 149.2 and -17.1
      to -101.3 for MH and ML selection, respectively. Cumulative standardized realized
      selection differentials, averaged for the three replicates, were 10.06 and -9.51
      for MH and ML selection, respectively. Direct responses (kcal.kg-.75.d-1) in heat
      loss after 15 generations were 44.2 for MH and -27.4 for ML as deviations from
      MC. Asymmetry of response was evident (P = .03) by Generation 10. Realized
      heritability was .28 +/- .01 based on divergence of MH and ML selection. For
      selection for higher and lower heat loss, realized heritabilities were .31 +/-
      .01 and .26 +/- .01, respectively.

PMID- 9250506
TI  - Divergent selection for heat loss in mice: II. Correlated responses in feed
      intake, body mass, body composition, and number born through fifteen generations.
AB  - Divergent selection for heat loss (kcal.kg-.75.d-1), measured in 9- to 11-wk-old
      male mice, was conducted for 15 generations. Selection for high (MH) and low (ML)
      heat loss and unselected control (MC) occurred in each of three replicates for a
      total of nine unique lines. Feed intake in males was measured during Generations
      9 through 15. Body mass at commencement of mating in females and at time of
      measurement of heat loss in males was recorded. Body fat percentage at 12 wk for
      animals of Generations 6, 10, and 14 was predicted as a function of electrical
      conductivity and body mass. Litter size was recorded for all generations, and
      components of litter size were evaluated at Generation 11 in one replicate and
      Generation 12 in the other two replicates. Feed intake changed in the same
      direction as heat loss for the MH and ML selections; at Generation 15, the
      difference between MH and ML (P < .002) was 20.6% of the MC mean. Body mass did
      not change with selection for heat loss. Differences in body fat percentage were
      not significant in earlier generations, but at Generation 14, MH and ML were
      significantly (P < .01) different with MH mice having the lowest fat percentage;
      MC was intermediate. Selection had a significant (MH vs ML; P < .01) effect on
      litter size, causing an increase in MH and a decrease in ML. This difference was
      explained by a difference (P < .01) in ovulation rate. There was no asymmetry of
      response in feed intake, fatness, litter size, or number of ovulations.

PMID- 9250507
TI  - Assessing the efficiency of multiplicative mixed model equations to account for
      heterogeneous variance across herds in carcass scan traits from beef cattle.
AB  - Data (n = 2,658) from live animal ultrasonic measures from 17 Angus herds were
      used to evaluate a multiplicative mixed model that incorporates scaling factors
      to correct for across-herd heterogeneity of variance. Traits included were ribeye
      muscle area (EMA), surface fat at the P8 site (P8), surface fat between the 12th
      and 13th ribs (RIB12), and weight at scanning (WEIGHT). Cattle ranged in age from
      501 to 698 d and represented 291 contemporary groups. Data were initially
      analyzed using single-trait, animal model, Method R procedures to estimate
      variance components and heritabilities (h2). These estimates were incorporated
      into a multiplicative mixed model that simultaneously estimates breeding values
      (EBV) and heterogeneity factors. Re-estimation of h2 after scaling the data with
      the correction factors was explored to obtain a measure of the improvement in the
      genetic evaluation and to detect changes in ranking of individuals and herds.
      Initial h2 estimates for EMA, P8, RIB12, and WEIGHT were .36, .39, .29, and .48,
      respectively. Scaling factors ranged from .25 for P8 in a herd with eight records
      to 1.96 for RIB12 in a herd with 86 individuals. Re-estimates of h2 increased by
      an average of 4.2% for all the traits as a result of correcting for
      heterogeneity. Deviations of new scaling factors were within expectations.
      Correlations between EBV with and without heterogeneity correction were greater
      than .97 for all the traits. However, some substantial re-rankings of herds were
      observed for some traits in the smaller herds.

PMID- 9250508
TI  - Evidence for quantitative trait loci affecting ovulation rate in pigs.
AB  - Fifty-five microsatellite markers were scored in an F2 population of pigs (n =
      114 females) developed at the University of Nebraska. The population was produced
      by crossing a line previously selected for 10 generations using an index of
      ovulation rate and embryonal survival and a line selected at random. The lines
      were from a common base population and differed by 6.7 ovulations and 3.1 fetuses
      at 50 d of gestation. Ovulation rate and number of fully formed and mummified
      pigs were recorded for each female. Data were analyzed with regression models
      that included random animal effects. Likelihood-ratio tests were used to test for
      quantitative trait loci (QTL) effects by deviating the log-likelihood for the
      full model that included additive and dominance QTL effects from the log
      likelihood for the reduced model that did not contain QTL effects. A QTL for
      ovulation rate was found on chromosome 8 (P < .001) with an additive effect of
      3.07 ovulations. Other evidence of potential QTL affecting ovulation rate was
      found on chromosomes 4 (P < .10), 13, and 15 (P < .05). Effects on chromosomes 4,
      13 and 15 were not significant for fan experiment-wise threshold value of P <
      .001. No significant QTL for litter size or number of mummified pigs were found.
      Additional data are needed to confirm the location and the effect of QTL found
      for ovulation rate before markers associated with them can be used in marker
      assisted selection.

PMID- 9250509
TI  - Effect of testosterone on differential muscle growth and on protein and nucleic
      acid concentrations in muscles of growing lambs.
AB  - Growth, nucleic acid, and protein concentrations were measured in three muscles
      of 20 rams, 20 wethers, and 20 wethers implanted with testosterone. Two lambs
      from each group were slaughtered at 14-d intervals from 49 to 133 d, and then at
      28-d intervals until 217 d, for a total of 10 slaughter ages. Immediately after
      slaughter, the semitendinosus, splenius, and triceps brachii muscles were
      removed, trimmed of adhering fat, and weighed. The DNA, RNA, and protein
      concentrations of these muscles were determined. Testosterone increased combined
      weight of the three muscles. The splenius muscles of rams and wethers implanted
      with testosterone were heavier and had a biphasic growth pattern as the combined
      muscle weight increased, whereas the splenius muscle of wethers had a single
      growth phase. Rams and implanted wethers had greater splenius muscle DNA and RNA
      concentrations than wethers as muscle weight increased. This model could be used
      to study the gene regulation of testosterone-induced muscle growth with the
      possibility of invoking similar effects in more economically important muscles.

PMID- 9250511
TI  - Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs
      following intraperitoneal injection of lipopolysaccharide.
AB  - The emerging view is that reduced feed intake, lean muscle accretion, and growth
      in immunologically challenged pigs is the result of increased cytokine activity,
      but this has not been directly tested. To begin addressing this issue, 72
      crossbred barrows and gilts (11.55 +/- .19 kg BW) were not fed for 12 h and then
      injected i.p. with 0, .5, or 5 micrograms/kg of Escherichia coli
      lipopolysaccharide (LPS). Blood was collected by jugular puncture at 0, 2, 4, 8,
      12, and 24 h after injection. Plasma levels of tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6), cortisol, plasma urea nitrogen (PUN), NEFA, and
      triglycerides were determined. Immunological stress was induced by LPS as
      indicated by increased secretion of TNF-alpha, IL-6, and cortisol. In pigs
      receiving 5 micrograms/kg of LPS, plasma TNF-alpha was increased 10-fold at 2 h
      after injection and was still elevated (P < .01) at 4 h. In these same pigs,
      plasma concentration of IL-6 was increased at 2 h and peaked at 4 h with levels
      exceeding baseline values by 200-fold (P < .01). Cortisol was elevated at 2, 4,
      and 8 h after injection (P < .01). The increased secretion of cytokines and
      cortisol in pigs injected with 5 micrograms/kg of LPS was followed by an increase
      in protein degradation, as evidenced by PUN values that were increased two- and
      threefold at 8 and 12 h after injection, respectively. However, unlike previous
      reports in laboratory animal species, plasma glucose, NEFA, and triglycerides
      were not altered by LPS. Nonetheless, as the period of feed deprivation
      progressed from 12 to 36 h, plasma NEFA and triglycerides increased (P < .05) and
      plasma glucose tended to decrease. We believe that immunological challenge
      induces cytokine synthesis and secretion in swine which, in turn, may induce
      protein catabolism.

PMID- 9250510
TI  - Effects of prenatal androgenization and lactation on adipose tissue metabolism in
      finishing single-calf heifers.
AB  - Twelve control (C) and 12 prenatally androgenized (PA) lactating (L) first-calf
      heifers and five (two C and three PA) similar, nonlactating (NL) heifers were
      used to assess the effects of PA and L on the metabolic activity of s.c. adipose
      tissue (AT). Heifers were fed an 85% concentrate diet, and their calves were
      weaned at 112 +/- 1 d of age. Adipose tissue was biopsied at approximately 77 d
      (period 1, during lactation for L heifers) and 126 d (period 2, after L heifers
      had calves weaned) postpartum. The NL heifers gained .22 kg/d faster (P = .20)
      and had greater fat deposition than L heifers during period 1. The PA heifers
      were fatter and gained 14.6% faster than C heifers during lactation. Epinephrine
      (E) and norepinephrine (NE) increased in vitro fatty acid (FA) release 25 (P <
      .01) and 15% (P < .06), respectively, above basal rates. Near-maximal release of
      FA, as estimated by stimulation with E plus theophylline plus adenosine deaminase
      (ETAD), was 73% (4,110 vs 2,379 +/- 161 nEq/[2 h.100 mg of tissue]; P < .01)
      above basal rates. Basal FA release was unaffected, but ETAD-stimulated rates
      were decreased (P < .04; 4,430 +/- 246 vs 3,789 +/- 209 nEq/[2 h.100 mg of
      tissue]) by PA. Stimulation of FA release by E (P = .22) or NE (P = .31) did not
      differ between C and PA. For NL heifers, PA decreased (P < .02) FA release, which
      corresponded with their greater fat deposition, but PA did not affect L heifers
      (PA x L interaction, P = .14). The content of NEFA in s.c. AT (pool size) was 34%
      greater (P < .01) during period 2 than during period 1. Pool size was not
      affected (P = .72) by NE but was increased by E (1,628 vs 1,777 +/- 92 nEq/100 mg
      of tissue; P < .05) and ETAD (1,628 vs 2,176 +/- 93 nEq/100 mg of tissue; P <
      .01). For L heifers, PA tended (P < .07) to increase incorporation of acetate
      into FA during period 1. Thus, PA resulted in subtle increases in lipogenesis and
      decreases in lipolysis during the first lactation-weaning cycle that were
      consistent with greater rates of gain and fat deposition.

PMID- 9250512
TI  - Consumer evaluation of beef of known categories of tenderness.
AB  - A study was conducted to determine consumer perceptions of beef top loin steaks
      of known shear force and to evaluate how buying trends were modified by the
      tenderness and price variations of these steaks. Strip loins were cut into a 2.54
      cm-thick steaks, and the center steak from each strip loin was used to determine
      Warner-Bratzler shear force. The remaining steaks were placed into one of the
      following shear force categories based on that shear force and color-coded
      accordingly: 1) 2.27 to 3.58 kg (Red); 2) 4.08 to 5.40 kg (White); and 3) 5.90 to
      7.21 kg (Blue). Randomly recruited consumers were allowed to evaluate steaks and
      then purchase steaks based on their findings. A $1.10/kg price difference was
      placed between each category. Results of the analysis indicated that consumers
      were able to differentiate between the three categories of tenderness (P < .05).
      In addition, consumers gave higher (P < .05) juiciness and flavor ratings to Red
      steaks than to Blue steaks. Overall satisfaction was higher (P < .05) for Red
      steaks than for the other two categories of steaks. The following percentages of
      steaks were purchased: 1) Red, 94.6%; 2) White, 3.6%; and 3) Blue, 1.8%. These
      results suggest that consumers could discern between categories of tenderness and
      were willing to pay a premium for improved tenderness.

PMID- 9250513
TI  - Influence of sire growth potential, time on feed, and growing-finishing strategy
      on cholesterol and fatty acids of the ground carcass and longissimus muscle of
      beef steers.
AB  - The purpose of this study was to determine how diverse beef cattle production
      systems affect fatty acids and cholesterol of meat. Crossbred cows were bred by
      AI to high (H) or moderate (M) growth rate potential bulls to produce spring- or
      fall-born calves. Steer calves from these matings were placed on finishing diets
      at three ages. Spring-born steers were started at 6 or 18 mo of age (A6 and A18),
      and fall-born calves were started at 12 mo of age (A12). Slaughter times were 0,
      90, 180, and 270 d for A6; 68, 136, and 204 d for A12; and 0, 45, 90, and 135 d
      for A18. Four steers of each type were slaughtered in each of 2 yr for each sire
      type x time on feed x slaughter group. Fatty acids and cholesterol of ground
      carcass and longissimus muscle (LM) were determined by GLC. Carcass fat increased
      faster in M than in H steers (P < .01). Ground carcass cholesterol was greater
      for M steers (P = .06) than for H steers because of the greater fat content in
      the M ground carcass. No differences in LM cholesterol were observed for sire
      growth potential or time on feed. Fatty acid differences in ground carcass with
      time on feed were due primarily to decreases in 18:0 and increases in 18:1. The
      LM saturated and monounsaturated fatty acids changed little with time on feed,
      but total saturates were greater for M steers (44.5%) than for H steers (42.8%)
      (P = .02). A18 steers of H sires had the greatest (P = .04) ratio of 18:0 plus
      unsaturates to 14:0 plus 16:0 (most hypocholesterolemic). We conclude that
      cholesterol in lean muscle is not altered by the sire growth potential x time on
      feed x growing-finishing strategy imposed, and that lean beef from steers sired
      by H bulls and backgrounded before finishing may produce meat with the healthiest
      lipid composition.

PMID- 9250514
TI  - The hydrodyne: a new process to improve beef tenderness.
AB  - The organoleptic trait most affecting consumer acceptance of beef is tenderness.
      The Hydrodyne process uses a small amount of explosive to generate a shock wave
      in water. The shock wave passes through (in fractions of a millisecond) objects
      in the water that are an acoustic match with water. Four beef muscles
      (longissimus, semimembranosus, biceps femoris, and semitendinosus) exposed to
      either 50, 75, or 100 g of explosives were significantly tenderized compared with
      controls. As much as a 72% reduction in shear force was observed for the
      longissimus muscle using 100 g of explosives. Reductions in shear force with
      magnitudes of 30 to 59% improvements were observed for the other three muscle
      types. Results suggest that tenderizing beef with the Hydrodyne process presents
      a potentially novel opportunity in the way the meat industry can tenderize meat.

PMID- 9250515
TI  - Comparison of USDA quality grade with tendertec for the assessment of beef
      palatability.
AB  - Carcasses (n = 265) selected to differ in USDA yield grade were evaluated by
      expert graders and assessed for tenderness with the Tendertec Mark III Beef
      Grading Instrument. Tendertec measurements were collected on longissimus lumborum
      muscles in both sides of each carcass. During fabrication of each left carcass
      side, a rib section (later converted into three steaks) was removed for aging and
      subsequent sensory panel evaluation at 14 d and for Warner-Bratzler shear force
      measurements at 14 and 28 d. Correlation coefficients for repeatability of
      Tendertec output variables, between left and right carcass sides, were .57, .44,
      .70, and .65 for Area-2, Area-2B, Power-2, and Power-2B, respectively.
      Correlations between Tendertec output variables and Warner-Bratzler shear force
      evaluations performed on steaks aged 14 or 28 d were not different from zero.
      Sensory panel ratings for amount of connective tissue were correlated (P < .01)
      with Tendertec output variables Area-2 and Area-2B (r = -.168 and -.154,
      respectively), and ratings for overall tenderness were correlated (P < .05) with
      the Area-2 output variable (r = -.131) but the coefficients were very low.
      Segregation analysis, using Tendertec output variables Area-2 and Power-2,
      significantly (P < .05) stratified sensory panel ratings for connective tissue
      amount and overall tenderness. Even though the Tendertec probe detected some
      differences in connective tissue contributions to rib steak tenderness, it was
      not better than USDA quality grade at segmenting A-maturity carcasses into
      anticipated tenderness outcomes, and thus its applicability as a grading
      instrument may be limited to use on more mature beef carcasses.

PMID- 9250516
TI  - Incubation temperature effects on physical characteristics of normal, dark, firm
      and dry, and halothane-carrier pork longissimus.
AB  - Pigs (n = 18) were selected to represent three different muscle conditions (six
      pigs per condition): normal: dark, firm, and dry; and halothane carrier. A 45-cm
      long longissimus section was excised from each side of the carcass at 30 min
      postmortem and cut into six sections. Right side sections were assigned to the
      intermediate temperature incubation (23 degrees C), and left side sections were
      designated high temperature incubation (40 degrees C). Sections were randomly
      assigned to incubation times (0, 1, 2, 4, 6, or 8 h). The 0 h section from each
      incubation treatment was designated as a control and was placed directly into a 4
      degree C cooler. Temperature and pH were evaluated on the control section and for
      each loin section a the end of the incubation time. Color (L*, a*, and b*
      values), percentage of purge loss, water-holding capacity, and drip loss were
      determined. Incubation treatment did not alter pH decline in dark, firm, and dry
      muscle; however, high temperature increased pH decline in normal and halothane
      carrier samples. Results suggest that there is a strong interaction between pH
      and temperature that affects pork quality attributes. High incubation temperature
      had a negative effect on most quality variables; however, muscle condition
      (normal or halothane carrier) had limited effects on muscle quality.

PMID- 9250517
TI  - Effect of dietary vitamin E supplementation on the integrity of skeletal muscle
      in exercised horses.
AB  - The effect of vitamin E intake on indicators of muscle integrity was studied in
      exercised horses. Nineteen horses were blocked by sex and then assigned to one of
      three diets: no supplemental vitamin E (BASAL), BASAL plus 80 IU of supplemental
      vitamin E/kg DM (80), or BASAL plus 300 IU of supplemental vitamin E/kg DM (300).
      The BASAL diet contained less than 44 IU of vitamin E/kg DM, but it was adequate
      in all other nutrients. During the 90-d treatment period, horses were exercised 5
      d/wk; in addition, serum and middle gluteal muscle alpha-tocopherol
      concentrations were measured at 0, 30, and 90 d. All horses performed a repeated
      submaximal exercise test (RSET) at the end of the 90-d period. The following were
      measured before and after the RSET: alpha-tocopherol, thiobarbituric acid
      reactive substances (TBARS), conjugated diene (CD) concentrations of the middle
      gluteal muscle, and serum creatine kinase (CK) and aspartate aminotransferase
      (AST) activities. Serum alpha-tocopherol concentrations of horses receiving the
      BASAL and 80 diets decreased (P < .05 and P < .06, respectively) during the 90-d
      treatment period but did not change in horses receiving the 300 diet. Serum and
      muscle alpha-tocopherol concentrations were higher (P < .05) at 30 and 90 d in
      horses receiving the 300 diet than in horses receiving the BASAL and 80 diets.
      Serum CK and AST activities increased (P < .05) following RSET but were not
      affected by dietary vitamin E level. Muscle alpha-tocopherol level did not affect
      muscle CD or TBARS.

PMID- 9250518
TI  - Marginal efficiency of free or protected crystalline L-tryptophan for tryptophan
      and protein accretion in early-weaned pigs.
AB  - We conducted an experiment to determine the efficiency of dietary tryptophan
      (Trp) for protein and Trp accretion in 4-kg (live weight) pigs. Five Trp
      deficient diets were fed for 18 d after weaning. The basal diet contained 23.4%
      protein and .14% Trp. The four other diets were similar to the basal diet but
      were supplemented with .06 or .12% free or protected crystalline Trp. No
      differences were found between the two crystalline Trp forms for all variables
      under study. Equal amounts of all diets were fed by intragastric tube feeding.
      Daily weight gain (P < .10), gain:feed (P < .05), and daily protein retention (P
      < .01) increased linearly as dietary Trp increased. Similarly, retention and
      gross efficiency (retained: intake) of almost all amino acids increased.
      Tryptophan retention also increased linearly (P < .05), but gross efficiency was
      maximal (40.1%) with protein-bound Trp from the basal diet, and it decreased
      linearly as dietary Trp increased. This important reduction was the result of a
      low marginal efficiency for crystalline (13.6 +/- 3.3%) free or protected Trp.

PMID- 9250519
TI  - Effect of folic acid supplementation on folate status and formate oxidation rate
      in mink (Mustela vision).
AB  - We investigated the folate-dependent toxicity of formate to mink to better
      understand the use of formic acid in fur animal feeds. Folic acid supplementation
      (0, 1, 5, 10, and 20 mg/kg of DM) in the feed of weanling mink for 4 wk resulted
      in hepatic tetrahydrofolate (H4folate) concentrations of 3.94, 8.51, 9.15, 10.4,
      and 15.0 nmol/g, respectively (SE 1.03). Oxidation tests in metabolic chambers,
      preceeding a single injection of sodium [14C]formate (500 mg/kg BW), showed that
      the nonsupplemented mink oxidized formate into CO2 at a rate 37% less than that
      of the supplemented mink. The oxidation rate increased with supplementation level
      and was maximal, 54.2 mEq.kg1.h1 (SE 3.0), at 10 mg of folate/kg; at the highest
      level of supplementation (20 mg/kg), CO2 production tended to be lower.
      Concentration of hepatic 14C increased with the hepatic H4folate, and its
      accumulation continued after the highest point of oxidation. These observations
      indicate that mink oxidize formate readily but at a slightly lower rate than do
      rats. However, if extra folate is not supplemented in the feed during the period
      of early intensive growth, hepatic H4folate level may decline to the levels found
      in humans and monkeys, which are susceptible to formate accumulation. Average
      daily weight gain improved with each increase in supplementation of folic acid;
      however, only the differences between the nonsupplemented diet and the two
      highest levels of the vitamin reached statistical significance (P < .05).

PMID- 9250520
TI  - The effect of reducing excess dietary amino acids on growing-finishing pig
      performance: an elevation of the ideal protein concept.
AB  - Seventy-two gilts were used to determine the effect of reducing excess amino acid
      intake on growing-finishing pig performance. Separate diets were formulated for
      the growing (20 to 55 kg BW) and finishing (55 to 100 kg BW) periods. For each
      period, three diets were formulated that varied in total crude protein level and
      contained similar levels of digestible ideal protein. Crystalline amino acids
      were added to the low protein diets to overcome potential deficiencies. The
      grower diets contained .66% apparent ileal digestible lysine and contained 16.6,
      15.0, and 13.0% CP, respectively; for the finisher diets, these values were .55%
      digestible lysine and 14.2, 12.8, and 11.0% CP, respectively. Amino acid analyses
      and a separate digestibility trial were conducted to confirm digestible amino
      acid levels in the dietary ingredients. During the growing and the overall
      growing-finishing period, daily gain, feed intake, and gain:feed were not
      affected (P > .10) by dietary treatment. Daily gain tended to be lower (P = .06)
      and gain:feed was poorer (P < .05) for pigs fed the 11.0% CP diet during the
      finishing phase. Although backfat thickness tended to be greater (P = .07) for
      pigs fed the lower-CP diet, estimated carcass lean yield was not affected (P >
      .10) by dietary treatment. Results of this study show that dietary CP can be
      reduced to 13% in the growing and 12.8% in the finishing diets of pigs as long as
      crystalline amino acids are added to match the apparent ileal digestible amino
      acid ratios in an assumed ideal protein.

PMID- 9250521
TI  - Body composition and protein and fat accretion in various body components in
      growing gilts fed diets with different protein levels but estimated to contain
      similar levels of ideal protein.
AB  - A comparative slaughter technique was used to determine the effect of dietary
      protein levels on body composition and protein and fat accretion in various body
      components in Yorkshire gilts. Diets were formulated to contain similar levels of
      idea protein. Eight gilts were slaughtered at 20 kg BW to determine initial body
      composition. Twenty-four gilts were assigned to each of three dietary treatments
      (16.6, 15.0 and 13.0% CP) during the growing period (20 to 55 kg BW). During the
      finishing period (55 to 100 kg BW), dietary CP levels were reduced by
      approximately two percentage units. Eight gilts per treatment were slaughtered at
      55 kg BW, and the remaining pigs were slaughtered at 100 kg BW. At slaughter, the
      pits were divided into three components: carcass, empty gastrointestinal tract,
      and other non-carcass parts. Half of the carcass was further dissected into
      retail cuts. None of the carcass retail cuts was affected (P > .10) by the
      dietary CP levels, except trimmed ham was smaller (P < .05) in gilts fed the 13%
      CP growing and 11% CP finishing diets. Far content in the empty body (P = .12)
      and in the carcass (P = .06) was highest and the empty body water accretion rate
      was lowest (P = .05) in gilts fed the 13% CP growing and 11% CP finishing diets.
      Other aspects of chemical body composition, protein and fat accretion rates, and
      estimated lean yields were not affected by dietary CP level (P > .10).

PMID- 9250522
TI  - Effects of dietary fat on follicular development and circulating concentrations
      of lipids, insulin, progesterone, estradiol-17 beta, 13,14-dihydro-15-keto
      prostaglandin F(2 alpha), and growth hormone in estrous cyclic Brahman cows.
AB  - Brahman cows were used to evaluate dietary fat (3.74% [control] and 5.20%
      [treated]) effects on blood hormone and lipid concentrations, follicular
      populations, and in vitro steroidogenesis. Cows were fed and ovaries were
      monitored by ultrasound from d 1 of the first estrous cycle (EC) until the first
      follicle of the second EC reached 8 mm, at which time ovaries were harvested.
      Follicular fluid (FF) was collected from large- and medium-sized follicles and
      assayed for progesterone (P4), estradiol-17 beta (E2), testosterone, cholesterol,
      and triglycerides. The corpus luteum was removed, minced, treated with LH, and
      incubated for 4 h. Granulosa cells harvested from the largest follicle were
      treated with forskolin, LH, or FSH and incubated for 48 h. Blood was collected
      during the treatment period and plasma assayed for 13,14-dihydro-15-keto
      prostaglandin F(2 alpha) (PGFM), growth hormone (GH), insulin, P4 and E2.
      Cholesterol and triglycerides were assayed only from blood samples collected
      every 7 d. Treated cows had greater (P < .01) plasma E2 during the first EC and
      greater (P < .01) P4 during the second EC than controls. Treated cows had
      elevated (P < .01) insulin following d 16 of treatment, but GH and triglycerides
      were similar (P > .10) in both treatment groups. Treated cows tended (P = .10) to
      have greater PGFM peak concentrations than controls. Plasma cholesterol was
      elevated (P < .01) in treated cows on d 7 of the first EC. Treated cows tended to
      have greater (P < .09) follicular populations during the ovulatory and first wave
      of the first and second EC. Treatment did not affect (P > .10) FF concentrations
      of P4, E2, testosterone, cholesterol, or triglyceride from either large- or
      medium-sized follicles. There were no differences (P > .10) in steroid hormones
      produced in vitro.

PMID- 9250523
TI  - Role of tumor necrosis factor-alpha in the ovulatory mechanism of ewes.
AB  - Tumor necrosis factor (TNF)-alpha was localized by indirect immunofluorescence
      microscopy to thecal endothelial cells or preovulatory ovine follicles.
      Immunostaining of endothelial cells within the apical hemisphere of the follicle
      declined abruptly with the approach of ovulation; cells within the counterpart
      basal follicular wall remained largely unaffected. It appeared that TNF alpha had
      been released into the presumptive area of follicular rupture. Intrafollicular
      injection of TNF alpha antiserum blocked ovulation in ewes. We considered the
      possibility that TNF alpha liberated from apical endothelial cells mediates the
      programmed deletion of ovarian surface and follicular cells that occurs within
      the formative ovulatory stigma of sheep. Indeed, contiguous ovarian surface
      epithelium, thecal endothelium, and granulosal cells were protected from
      apoptotic death (DNA fragmentation) by exposure to TNF alpha antibodies. Finally,
      TNF alpha induced ovarian cell apoptosis in vitro. We suggest that a bioactive,
      soluble form of TNF alpha generated from endothelial cells of preovulatory ovine
      follicles has an obligatory role in the biomechanics of apical follicular
      weakening and ovarian rupture.

PMID- 9250524
TI  - Effect of age and pattern of gain on induction of puberty with a progestin in
      beef heifers.
AB  - Crossbred heifers (n = 75) fed for rapid (R; .82 kg/d) or slow-then-rapid (SR;
      .41 kg/d for 90 d then .82 kg/d) postweaning gain were used to examine the
      effects of age or pattern of gain on induction of puberty by a progestin. At 9.5,
      11.0, and 12.5 mo of age, 12 prepuberal heifers from each growth treatment
      received progestin (a 6-mg Norgestomet implant for 10 d) or control treatments.
      Induction of puberty, LH secretory profiles, and ovarian follicular
      characteristics were assessed in Norgestomet-treated and control heifers. Body
      weights of R heifers were greater (P < .01) than those of SR heifers at all ages.
      At 12.5 mo, more Norgestomet-treated heifers exhibited a puberal estrus within 5
      d after implant removal compared with controls (82% vs 9%, respectively), but
      Norgestomet did not induce puberty at 9.5 or 11 mo of age (progestin x age, P <
      .05) in heifers of either gain pattern. Norgestomet increased (P < .01) LH pulse
      frequency at all ages, whereas Norgestomet increased only mean LH concentrations
      at 12.5 mo of age (progestin x age, P < .03). Norgestomet treatment altered (P <
      .01) ovarian follicular characteristics at all ages. Gain pattern did not affect
      (P > .1) LH secretory profiles, ovarian characteristics, or induction of puberty
      by Norgestomet. We conclude that progestins induce puberty by hastening the
      normal cascade of endocrine and ovarian events associated with spontaneous
      puberty. Furthermore, age, but not pattern of gain, seems to be the critical
      factor influencing the efficacy of progestins to induce puberty in heifers.

PMID- 9250525
TI  - Effect of dietary phenolic amines on testicular function and luteinizing hormone
      secretion in male angora goats.
AB  - To test the effect of dietary phenolic amines on pituitary-gonadal functions, 24
      postpubertal male Angora goats were assigned during the breeding season to a
      control diet or to graze on a pasture dominated by phenolic amine-containing
      vegetation (PA). Compared with control bucks, bucks grazing PA had decreased (P <
      .001) serum concentrations of testosterone, increased (P < .001) triiodothyronine
      (T3) and thyroxine (T4), greater (P < .001) reduction in scrotal circumference
      (SC), lower (P < .001) body weight gains, and reduced (P < .01) semen volume.
      Sperm concentration and progressive motility were not affected by treatment. On d
      75 of treatment, endogenous and GnRH-stimulated LH secretion were greater (P <
      .01), but endogenous and stimulated testosterone secretion tended (P < .10) to be
      reduced in the PA bucks relative to the controls. Endogenous serum concentrations
      of LH and testosterone were positively correlated in the controls, whereas no
      correlation was detected in the PA males. We conclude that during the breeding
      season, increased consumption of plants with a high concentration of phenolic
      amines can affect the reproductive competence of male goats in a manner that
      suggests a premature ending of the active reproductive phase. The concurrent
      influence of dietary phenolic amines on serum T3 and T4, and the relationship of
      these hormones with expression of seasonal reproduction in domestic and wild
      ruminants, warrants further analysis of the relationship between dietary phenolic
      amines, thyroid function, and reproduction in these species.

PMID- 9250527
TI  - Intake, digestion, and nitrogen utilization by sheep fed tropical legumes with
      contrasting tannin concentration and astringency.
AB  - We conducted an experiment to determine the effects of concentration and
      astringency of extractable and bound condensed tannins (CT) in tropical legumes
      on intake, digestibility, and nitrogen (N) utilization by sheep. The test legumes
      (Desmodium ovalifolium and Flemingia macrophylla) had similar concentrations of
      extractable CT (90 g/kg DM) but different concentrations of bound CT and
      astringency of tannins. Chopped, sun-dried forage of each legume was sprayed with
      either water (control) or polyethylene glycol (PEG, 35 g/kg of DM) to bind
      extractable CT and fed daily (26 g/kg BW) to eight sheep with ruminal and
      duodenal cannulas. The sheep also received starch-extracted cassava meal
      intraruminally (4 g/kg BW) as a constant source of readily fermentable
      carbohydrates. Intake of the two legumes was not different (P > .05), but it
      increased an average of 10% (P < .01) when extractable CT were reduced from 90 to
      50 g/kg of DM with PEG. Ruminal and total tract digestibilities of OM, NDF, and
      ADF were greater (P < .01) with D. ovalifolium than with F. macrophylla and
      increased for both legumes with the addition of PEG. Greater (P < .01) N flow to
      the duodenum, N absorbed from the intestine, and fecal N were observed with F.
      macrophylla than with D. ovalifolium. Extraction of CT with PEG resulted in less
      (P < .05) ruminal escape protein and less (P < .01) fecal N with both legumes,
      but apparent postruminal N digestion was not affected. Changes in the
      concentration of extractable CT in tropical legumes can significantly affect
      forage intake, digestion, and N utilization by sheep.

PMID- 9250526
TI  - Regulation of uterine immune function during the estrous cycle and in response to
      infectious bacteria in sheep.
AB  - Uterine infections are a major reproductive problem in livestock. We conducted
      two experiments to investigate factors that may modulate uterine responses to
      infectious bacteria. In Exp. 1, ewes received intrauterine inoculations of either
      saline or bacteria (75 x 10(7) cfu of Actinomyces pyogenes and 35 x 10(7) cfu of
      Escherichia coli) on either d 0 or 7 of the estrous cycle. Vena caval samples
      containing uteroovarian blood were collected twice daily from 12 h before until 6
      d after inoculation. Only ewes inoculated with bacteria on d 7 developed
      infections. Basal (4.8 vs .4 pmol), lipopolysaccharide-stimulated (14.2 vs 6.1
      pmol), and concanavalin A-stimulated (65.8 vs 21.6 pmol) blastogenesis (i.e.,
      [3H]thymidine incorporation) of vena caval lymphocytes was greater (P < or =
      .002) for ewes inoculated with bacteria or saline on d 0 rather than on d 7. The
      number (per 100 white blood cells) of lymphocytes was greater (41.3 vs 30.8, P <
      .001) and that of neutrophils was less (42.5 vs 51.6, P < .001) in ewes
      inoculated on d 0 rather than d 7. Bacteria increased (P < .05) vena caval PGF(2
      alpha) but not PGE2 concentrations. In Exp. 2, two protein fractions (molecular
      weights of > or = 100 kDa and approximately 12.7 kDa) from chromatography of
      uterine flushings collected on d 0 or 7, or 18 d after ovariectomy on d 0 or 7,
      modulated phytohemagglutinin-stimulated blastogenesis; the heavier fraction from
      d 0 had a stimulatory component, but the major effects of the fractions were
      inhibitory. The differences in immune function and regulation between d 0 and 7
      probably explain how the uterus of follicular phase ewes was able to prevent the
      development of an infection.

PMID- 9250528
TI  - The utilization of multidimensional scaling to identify forage characteristics
      associated with preference in sheep.
AB  - Forage preference is difficult to assess but is likely an important factor in
      determining DM intake. In two experiments, six sheep (wethers, Exp. 1; ewes, Exp.
      2) were used to obtain preference ratings on nine hays (Exp. 1) or nine fresh
      forages (Exp. 2). The statistical procedure of multidimensional scaling was used
      to develop orthogonal dimensions to account for the observed variation in
      preference for hays and fresh forages. This analysis produced three dimensions
      that accounted for 54% of the variation in mean 3-d preference for hays (Exp. 1).
      The three dimensions were subsequently associated by regression analysis with
      seven compositional variables. These were IVDMD and concentrations of
      monosaccharides, short-chain polysaccharides (SCP), and disaccharides in
      dimension 1(R2 = .99); acid detergent insoluble ash (ADIA) concentration,
      monosaccharide and SCP concentrations, and masticate NDF in dimension 2 (R2 =
      .99); and disaccharide and starch concentrations in dimension 3 (R2 = .65). Three
      dimensions accounting for 51% of the variation in fresh forage preference were
      found and related to four variables by regression analysis. These were
      disaccharide concentration and median particle size in dimension 1 (R2 = .76) and
      starch and monosaccharide + disaccharide concentrations in dimension 3 (R2 =
      .97). No physicochemical variables analyzed in this study were found to be
      significantly associated with the coordinates for the forages in dimension 2.
      Multidimensional scaling accounted for more than half the observed variation in
      animal preference and, in all but one case, these dimensions could be associated
      with physicochemical characteristics of the forages.

PMID- 9250529
TI  - Digestibility, apparent mineral absorption, and voluntary intake by horses fed
      alfalfa, tall fescue, and caucasian bluestem.
AB  - Alfalfa (Medicago sativa L.), low-endophyte (< 5%) tall fescue (Festuca
      arundinacea Schreb.), and caucasian bluestem (Bothriochloa caucasica [Trin.] C.E.
      Hubbard) were fed as chopped hay to six Arabian geldings (BW 441 kg; SE 2) in
      intake and digestibility experiments to determine nutritional value for horses at
      maintenance. Each experimental design was a replicated Latin square. Alfalfa was
      higher in DM and CP digestibility, IVDMD, apparent absorption of Ca, K, and S,
      and voluntary intake than the grasses (P < .05). Caucasian bluestem was higher in
      Zn but was lower in CP, TNC, Mg, P, K, S, and Cu concentrations than tall fescue.
      Crude protein digestibility and apparent absorption of Mg, K, and S were higher
      (P < .05) for tall fescue than for caucasian bluestem. Geldings fed alfalfa for
      ad libitum intake had higher serum concentrations of vitamin A, blood urea
      nitrogen, P, S, and Cu than geldings fed grass hays. Serum Zn was higher (P <
      .05), whole blood Se tended to be higher (P < .06), and BUN was lower (P < .05)
      in geldings fed caucasian bluestem than in those fed tall fescue. All forages met
      requirements for CP, Ca, Mg, K, and Fe when fed for ad libitum intake but were
      deficient in Cu for horses at maintenance. Caucasian bluestem was borderline in
      CP and was deficient in P but was the only forage that met the Zn requirement for
      the horses. Based on these results, caucasian bluestem could be a useful hay for
      horses but may require supplementation of CP and P.

PMID- 9250530
TI  - Dietary vitamin E and selenium affect mastitis and milk quality.
AB  - Vitamin E and selenium (SE) are essential nutrients that are integral components
      of the antioxidant defense of tissues and cells. Soils in many of the important
      dairy regions of the world are Se-deficient, and feedstuffs grown on these soils
      will not provide adequate dietary Se. Cattle consuming stored forages are likely
      to be low in vitamin E unless supplemented, and vitamin E deficiencies are
      frequently observed in peripartum dairy cows. Many new intramammary infections
      (IMI) occur in the 2 wk before and after calving. Deficiencies of either vitamin
      E or Se have been associated with increased incidence and severity of IMI,
      increased clinical mastitis cases, and higher somatic cell counts (SCC) in
      individual cows and bulk tank milk. Somatic cell counts are a primary indicator
      of mastitis and milk quality in dairy herds. The polymorphonuclear neutrophil
      (PMN) is a major defensive mechanism against infection in the bovine mammary
      gland. A know consequence of vitamin E and Se deficiency is impaired PMN activity
      and postpartum vitamin E deficiencies are frequently observed in dairy cows.
      Dietary supplementation of cows with Se and vitamin E results in a more rapid PMN
      influx into milk following intramammary bacterial challenge and increased
      intracellular kill of ingested bacteria by PMN. Subcutaneous injections of
      vitamin E approximately 10 and 5 d before calving successfully elevated PMN alpha
      tocopherol concentrations during the periparturient period and negated the
      suppressed intracellular kill of bacteria by PMN that commonly is observed around
      calving.

PMID- 9250531
TI  - Cottonseed meal or feather meal supplementation of ammoniated tropical grass hay
      for yearling cattle.
AB  - Despite high N intake by cattle consuming ammoniated forages, improvements in ADG
      might be expected be feeding proteins that supply ruminally available and(or)
      undegraded intake protein. Growth studies with 220-kg steers were conducted to
      evaluate ammoniated hay plus a liquid cane molasses-based supplement containing
      urea or a combination of urea and .07, .14, or .21 kg of CP daily from cottonseed
      meal (CSM) or feather meal (FM). Steers grazed dormant pasture and were fed hay
      plus 1.36 kg of DM daily per steer of the supplement. In each of 3 yr, total DM
      intake was similar (P > .60) among treatments, averaging 3.0% of BW. Daily gain
      by steers supplemented with urea and maximum ADG were similar across years,
      ranging from .21 to .23 kg and .50 to .60 kg, respectively. In all years for CSM
      supplementation, and in two of the three years for FM supplementation, increasing
      level of CP supplementation resulted in linear (P < .01) increases in ADG and
      gain:feed ratio (GF), with no differences (P > .10) between the protein sources.
      In one year, ADG and GF by steers supplemented with FM were maximized at the .07
      kg of CP level, suggesting greater efficiency of protein utilization in FM.
      Improved performance by cattle fed ammoniated tropical grass hay may be obtained
      by feeding a protein supplement that provides preformed protein that is either
      moderately or highly resistant to ruminal degradation. Ruminal degradation
      characteristics of protein sources may influence efficiency of protein
      utilization in cattle fed ammoniated tropical grass hay plus molasses-based
      supplements.

PMID- 9250532
TI  - Effect of ruminally degraded protein on protein available at the intestine
      assessed using blood amino acid concentrations.
AB  - The effect of increasing amounts of ruminally degraded protein on protein
      available at the intestine was studied using the concentration of blood plasma
      branched-chain amino acids as an indicator of protein flow to the small
      intestine. Five ruminally cannulated cows in midlactation were used in a 5 X 5
      Latin square design experiment and were fed a diet containing 20% alfalfa silage,
      40% corn silage, 30% shelled, coarsely ground corn, and 8% soybean meal (DM
      basis). Each experimental period was 17 d. Each period contained subperiods: 1 (5
      d), 2 (5 d), and 3 (7 d). In addition to the basal diet, cows were given casein
      infusions of 0, .5, 1.0, and 2.0 kg/d. During subperiod 1, the full amount of
      casein was infused into the abomasum (A100); in subperiod 2, 10% of each casein
      level was infused into the abomasum (A10); and, during subperiod 3, the full
      amount of casein was infused into the rumen (R100). The concentration of branched
      chain amino acids (Ile, Leu, and Val) in blood plasma increased as amounts of
      casein infused into the abomasum increased to the full amount. There was no
      increase in branch-chain amino acids when the same amount of casein was infused
      into the rumen, suggesting that ruminally degraded protein was adequate in the
      basal diet and the increased supply of degraded protein from ruminally infused
      casein did not increase the flow of protein to the small intestine.

PMID- 9250533
TI  - Response of lactating dairy cows to various densities of sorghum grain.
AB  - To examine the effects of various densities of sorghum grain resulting in graded
      levels of ruminally degradable starch on lactational performance, 32 lactating
      Holstein cows (90 d in milk [DIM]) were assigned to four treatments for 58 d.
      Diets contained 37% alfalfa hay, 3% cottonseed hulls, 10% whole cottonseed, 6%
      soybean meal, 5% of a molasses-mineral-vitamin supplement, and 39% sorghum grain.
      Treatments were dry-rolled sorghum (DRS) at 643 g/L or stream-flaked sorghum (SF)
      at 437, 360, and 283 g/L. Dry matter intake was highest for DRS followed by
      SF360, with the linear (P < .01) and cubic (P < .05) effects significant. The
      linear decrease in milk (P < .05) and 3.5% fat corrected milk (FCM, P < .025)
      with decreased density of sorghum was because of large decreases on SF283. Steam
      flaking increased total tract digestibilities of DM, OM, CP, starch, and ADF when
      compared with dry-rolling. Efficiency of conversion of feed DM to FCM and feed CP
      to milk protein were greater for sorghum flaked at 437 and 360 g/L than for DRS
      or the 283 g/L flake. The 283 g/L flake decreased DMI, milk yield, and milk fat
      percentage. Addition of buffer (1% NaHCO3) tended to ameliorate the decrease in
      DMI. These data show greater efficiency of feed utilization and conversion of
      feed CP to milk protein in cows fed sorghum grain flaked at 437 and 360 g/L
      compared with those fed dry-rolled sorghum or that flaked at 283 g/L.

PMID- 9250534
TI  - Rapid communication: a restriction fragment length polymorphism in the ovine
      Prolactin gene.

PMID- 9250535
TI  - Trimethylcolchicinic acid decreases liver fibrosis and cholestasis induced by
      prolonged biliary obstruction in the rat.
AB  - Colchicine is effective in decreasing hepatic fibrosis. However, several toxic
      reactions have been reported after colchicine treatment which are attributed to
      its ability to bind tubulin. The aim of this work is to determine if
      trimethylcolchicinic acid, which does not bind tubulin, is able to decrease
      experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile
      duct was ligated. Administration of trimethylcolchicinic acid (TMCA, 100
      micrograms rat-1 day-1, p.o.) began 4 weeks after biliary obstruction and
      continued for a further 4 weeks. The liver was used for histological and
      ultrastructural analysis and for collagen quantification (hydroxyproline
      content). The degradation of Matrigel and collagen (types I and III), as well as
      plasminogen activator activity, was determined in liver homogenates. Bilirubins
      and enzyme activities were measured in serum. Trimethylcolchicinic acid was able
      to improve normal liver histology, ultrastructure, collagen content and
      biochemical markers of liver damage. It also increased matrigel degradation and
      plasminogen activator activity. The mechanism of TMCA is probably associated with
      its ability to increase Matrigel degradation; however, other actions cannot be
      discarded.

PMID- 9250536
TI  - Percutaneous absorption and metabolism of Coumarin in human and rat skin.
AB  - Coumarin is widely used as a fragrance in cosmetics, perfumes and soaps. The food
      and Drug Administration banned coumarin use in food because of reports that
      coumarin produced hepatotoxicity in rodents. Concerns about coumarin's safety
      have also been raised by toxicity testing conducted by the National Toxicology
      Program. Therefore, we initiated studies to measure the extent of coumarin
      absorption and metabolism in skin. [14C]Coumarin (ca. 0.5 microCi per cell)
      absorption in skin was measured by using two vehicles: ethanol (15 microliters cm
      2) and an oil-in-water emulsion (3 mg cm-2). Absorption was determined for 24 h
      by using flow-through diffusion cells (0.64 cm2, exposed skin) with a receptor
      fluid consisting of HEPES-buffered Hank's balanced salt solution (pH 7.4).
      Coumarin metabolism was determined by high-performance liquid chromatography
      methodology. In rat skin (n = 3), the percentages of applied dose absorbed after
      24 h were 54.9 +/- 0.63 (mean +/- SEM) and 86.8 +/- 5.4 for the ethanol and
      emulsion vehicles, respectively, with ca. 5% remaining in skin. In human skin (n
      = 2), the percentages of applied dose absorbed after 24 h were 64.4 +/- 0.29 and
      98.0 +/- 5.3 for the ethanol and emulsion vehicles, respectively, with ca. 1%
      remaining in skin. The extent of skin absorption was greater from the emulsion
      vehicle than from the ethanol vehicle in both human and rat skin. Coumarin
      rapidly penetrated both rat and human skin with > 75% and > 95%, respectively, of
      the absorbed dose found in the receptor fluid within 6 h. No evidence of coumarin
      metabolism was found in either skin or receptor fluid fractions. These studies
      indicate that coumarin absorption is significant in skin. Systemic coumarin
      absorption must be expected after dermal contact with coumarin-containing
      products.

PMID- 9250537
TI  - Toxicity of furfuryl alcohol to F344 rats and B6C3F1 mice exposed by inhalation.
AB  - Groups of F344 rats and B6C3F1 mice were exposed to furfuryl alcohol vapor for 6
      hours per day, 5 days per week for 14 days (0, 16, 31, 63, 125, 250 ppm) or 13
      weeks (0, 2, 4, 8, 16, 32 ppm). Reduced survival was observed in the 14-day study
      at 250 ppm. Final mean body weights of rats and mice exposed to 125 ppm and of
      female mice exposed to 63 ppm were lower than controls at the end of the 14-day
      study; there were no significant differences in mean body weight among chemical
      exposed and control groups in the 13-week study. Exposure to furfuryl alcohol had
      no toxicologically significant effect on organ weights in either rats or mice,
      and did not cause any adverse changes in hematology or serum chemistry parameters
      evaluated in rates in the 13-week study. Microscopic lesions associated with
      exposure to furfuryl alcohol were present in the nose of both rats and mice at
      all exposure concentrations in both the 14-day and 13-week studies. Lesions
      observed in the 14-day study consisted of inflammation of the nasal turbinates
      accompanied by necrosis and squamous metaplasia of the respiratory epithelium and
      necrosis and degeneration of the olfactory epithelium. Similar lesions were
      observed in both rats and mice in the 13-week study. In addition, squamous
      metaplasia and goblet cell hyperplasia of the respiratory epithelium, squamous
      metaplasia of the transitional epithelium and degeneration, hyperplasia and some
      respiratory metaplasia of the olfactory epithelium were also observed in rats in
      the 13-week study, and hyaline droplets in the respiratory epithelium and chronic
      inflammation and respiratory metaplasia in the olfactory epithelium were observed
      in mice in the 13-week study. In general the nasal passages of mice appeared less
      sensitive than those of rats at the concentrations used in the 13-week study; a
      no-observable-effect level was not achieved in either the 14-day or the 13-week
      study.

PMID- 9250538
TI  - Evaluation of the porphyrinogenic risk of antineoplastics.
AB  - The use of antineoplastics is common in cancer therapy, and some of them have
      been associated with the development of porphyria in patients with cancer.
      However, knowledge of their effects on the haeme metabolic pathway is at present
      scarce and unclear. So, the present study evaluates the porphyrinogenic ability
      of nine antineoplastics (both alkylating and non-alkylating). These were tested
      either alone or in conjunction with 3,5-diethoxycarbonyl-1,4-dihydrocollidine
      (latent porphyria model) in chick embryos and in mice. The results obtained
      suggest that the use of cyclophosphamide, azathioprine, 5-fluorouracil,
      busulphan, procarbazine and hexamethylmelamine be avoided in the treatment of
      porphyric patients. On the other hand, dacarbazine, chlorambucil and melphalan
      are non-porphyrinogenic. We also provide evidence showing that neither the
      presence of the mustard group in the structure of the antineoplastic nor
      alterations in ferrochelatase or protoporphyrinogen oxidase activities are
      responsible for the porphyrinogenic ability of cyclophosphamide.

PMID- 9250539
TI  - Biological monitoring of occupational exposure to isoflurane by measurement of
      isoflurane exhaled breath.
AB  - The relationship between isoflurane environmental concentrations in operating
      rooms and the corresponding isoflurane concentration in the exhaled air of the
      operating personnel at the end of the exposure has been investigated. Isoflurane
      was retained in an adsorbent cartridge and after thermal desorption the
      concentration was estimated by gas chromatography. Significant correlation
      between environmental and exhaled air isoflurane concentrations allowed the
      establishment of a biological exposure index and biological exposure limits
      corresponding to proposed atmospheric threshold values.

PMID- 9250540
TI  - Rat embryo culture using rabbit serum as a medium for developmental toxicity
      studies.
AB  - The usefulness of rabbit serum as a culture medium for postimplantation rat
      embryos was examined. Rat embryos at day 9.5 of gestation were cultured in a
      mixture of rat and rabbit sera at various ratios (v/v) for 48 h. In 100% rat
      serum, a usual medium, rat embryos grew well. On the contrary, rat embryos died
      with little growth in 100% rabbit serum. In 75% rabbit and 25% rat sera, rat
      embryos grew but were morphologically abnormal. In 50% rabbit and 50% rat serum,
      however, rat embryos grew well showing no morphological abnormalities, as in 100%
      rat serum. It was concluded from these results that rabbit serum could be used at
      a proportion up to 50% as a medium for postimplantation rat embryo culture in a
      mixed form with rat serum. The rat embryo culture using rabbit serum as a medium
      would be useful in developmental toxicity studies, especially those involving
      species differences and toxicokinetics.

PMID- 9250541
TI  - Interaction of exercise training and chronic ethanol ingestion on hepatic and
      plasma antioxidant system in rat.
AB  - This study was undertaken in order to investigate the interactive effects of
      exercise training and chronic ethanol consumption on the antioxidant system in
      rat liver and plasma. Fisher-344 rats were treated in separate groups as follows:
      sedentary control (SC); exercise training (ET) for 6.5 weeks; ethanol 20% (2.0 g
      kg-1, p.o.) for 6.5 weeks; and ET and ethanol administration. In liver, ET
      significantly decreased the malondialdehyde (MDA) level (73% of SC). Chronic
      ethanol significantly increased catalase (CAT) activity and MDA levels (126% and
      135% of SC), respectively, and also depleted the reduced glutathione (GSH) level
      and the reduced to oxidized glutathione (GSH/GSSG) ratio (81% and 38% of SC),
      respectively. Exercise training plus ethanol significantly increased CAT and
      glutathione reductase (GR) activity (126% and 118% of SC), respectively, and
      decreased the MDA level (67% of SC). In plasma, ethanol significantly enhanced
      CAT activity and MDA levels (173% and 221% of SC), respectively. Ethanol
      ingestion also increased the CAT/superoxide dismutase (SOD) ratio (216% of SC) in
      plasma. Training plus ethanol ingestion significantly increased CAT activity and
      MDA levels (208% and 148% of SC), respectively, and increased CAT/SOD and
      glutathione peroxidase (GSH-Px)/SOD ratios (279% and 142% of SC), respectively.
      The data indicate that the combination of exercise and ethanol ingestion resulted
      in an enhanced hepatic CAT and GR activity to eliminate H2O2 and to maintain
      endogenous GSH levels. Thus, training ameliorated the ethanol-induced oxidative
      injury in the liver. The ratio of CAT/SOD in plasma increased twofold due to
      chronic ethanol intake and threefold due to the combination, which may be used as
      an index of oxidative stress.

PMID- 9250542
TI  - Pharmacogenetics and heart failure: a convergence with carvedilol.

PMID- 9250543
TI  - Generic warfarin: implications for patient care.

PMID- 9250544
TI  - Meropenem, a new carbapenem antibiotic.
AB  - Meropenem is the second carbapenem antibiotic available in the United States. It
      has a broad spectrum of activity that includes moderate activity against gram
      positive bacteria and excellent gram-negative aerobic and anaerobic activity.
      Meropenem has enhanced gram-negative activity relative to imipenem-cilastatin and
      often retains activity against strains resistant to third-generation
      cephalosporins and imipenem-cilastatin. The drug penetrates well into most body
      fluids and tissues, including cerebrospinal fluid. It is also stable against
      renal dehydropeptidase hydrolysis and does not require coadministration of a
      dehydropeptidase inhibitor. Meropenem showed excellent efficacy in clinical
      studies involving seriously ill patients with intraabdominal, central nervous
      system, lower respiratory tract, skin and soft tissue, urinary tract, and febrile
      neutropenic infections. It appears well tolerated and, relative to imipenem
      cilastatin, may have reduced potential for causing seizures and other central
      nervous system toxicities. Although it has many favorable qualities and some
      potential advantages relative to other broad-spectrum agents, additional trials
      and clinical experience are necessary to define its optimal place in clinical
      practice.

PMID- 9250545
TI  - Kaposi's sarcoma: advances in tumor biology and pharmacotherapy.
AB  - Kaposi's sarcoma (KS) is a highly vascularized neoplasm that primarily results in
      raised, highly vascularized lesions. Before the 1980s, KS was a rare disorder
      that occurred predominantly in elderly men of Mediterranean or Eastern European
      Jewish descent. With the advent of the acquired immunodeficiency syndrome (AIDS)
      epidemic, its occurrence has increased dramatically. It can be classified into
      four types: classic, African endemic, iatrogenic or drug associated, and AIDS
      related. Classic KS usually follows an indolent and benign clinical course that
      rarely requires treatment. In contrast, AIDS-KS is a fulminant disease that
      requires aggressive pharmacotherapy, especially when it involves visceral organs.
      The epidemiology, clinical presentation, pathogenesis, and management strategies
      of AIDS-KS are reviewed, including recent pharmacologic advances.

PMID- 9250546
TI  - A review of the effects of plasmapheresis on drug clearance.
AB  - Plasmapheresis (PP) is being increasingly performed to treat a number of
      infectious, immunologic, metabolic, and inherited illnesses. In this procedure,
      plasma and cellular components of blood are separated, and all solutes in plasma,
      including drugs, can be removed. The effects of PP on the pharmacokinetics of
      drugs administered therapeutically and taken in overdose are evolving. As the
      procedure becomes more widely performed, it is important that these effects be
      understood.

PMID- 9250547
TI  - Prevention and treatment of hemorrhagic cystitis.
AB  - Hemorrhagic cystitis is a syndrome associated with certain disease states as well
      as exposure to drugs, viruses, and toxins. It manifests as diffuse bleeding of
      the endothelial lining of the bladder. Treatment includes intravesical, systemic,
      and nonpharmacologic therapies, all of which have advantages and disadvantages.

PMID- 9250548
TI  - Ceftibuten: an overview.
AB  - Ceftibuten is an orally active third-generation cephalosporin that exhibits good
      microbiologic activity against many gram-negative and select gram-positive
      organisms. It is stable against plasmid-mediated beta-lactamases, including
      extended-spectrum beta-lactamases. Ceftibuten has been shown to be effective in
      the treatment of upper and lower respiratory tract infections and, although not
      approved indications, complicated and uncomplicated urinary tract infections in
      both adults and children. It is readily absorbed (75-90%) after oral
      administration, with peak serum levels of 17 microg/ml in healthy volunteers. Its
      half-life is 2.5 hours in healthy volunteers and is increased in elderly patients
      to approximately 3.2 hours. Elimination occurs primarily through the kidneys,
      requiring dosage adjustments to be made when creatinine clearance falls below 50
      ml/minute. The drug's safety profile is favorable and similar to that of most
      other cephalosporins. Based on pharmacokinetic information and clinical trial
      data, ceftibuten can be dosed once/day for most infections. It is an alternative
      to other currently available antimicrobial agents in the treatment of indicated
      upper and lower respiratory tract infections.

PMID- 9250549
TI  - A review of epidemiologic research on drug-induced acute liver injury using the
      general practice research data base in the United Kingdom.
AB  - Drug hepatotoxicities have been evaluated in case histories, surveys based on
      retrospective record reviews, and spontaneous adverse drug reactions reported to
      national pharmacovigilance systems, but in relatively few epidemiologic studies.
      To identify and quantify the risk of acute liver injury associated with
      individual drugs, we reviewed and integrated all the published epidemiologic
      research on the subject. The source population for the eight studies was general
      population registered on a single large general practice-based computerized data
      base. All were retrospective cohort studies, but some had a case-control design
      nested within the source cohort. Participants were selected according to their
      use of selected agents (nonsteroidal antiinflammatory drugs [NSAIDs],
      antibiotics, acid-suppressing drugs, other drugs suspected of being hepatotoxic)
      during the study period. Among the agents, we found a group of important
      hepatotoxic drugs with an associated incidence rate of acute liver injury greater
      than 100/100,000 users, including chlorpromazine and isoniazid. Agents with less
      risk but greater than 10/100,000 users were amoxicillin-clavulanic acid and
      cimetidine. A third group of drugs had an associated incidence rate of acute
      liver injury of less than 10/100,000 users. Our results provide evidence of
      relative safety for commonly administered agents such as NSAIDs, amoxicillin,
      omeprazole, and ranitidine. We also quantified important suspected liver
      toxicity, providing a reasonable precise risk estimate of clinical liver injury
      associated with chlorpromazine, isoniazid, and amoxicillin-clavulanic acid.

PMID- 9250550
TI  - Symptomatic cardiotoxicity associated with 5-fluorouracil.
AB  - A prospective cohort study was conducted in 35 hospitals with oncology units to
      determine the incidence of symptomatic cardiotoxicity in patients receiving
      continuous infusions of 5-fluorouracil (5-FU), and to identify risk factors that
      could contribute to the development of 5-FU-associated cardiotoxicity. A sample
      of 483 patients [197 (41%) women, overall average age +/- SD 60.9 +/- 11.9 yrs]
      were followed for one cycle of 5-FU infusion. Thirty-eight (7.9%) patients had
      abrupt termination of the infusion. There were 9 (1.9%) cases of suspected or
      documented cardiotoxic events. Cardiotoxicity occurred in 7 (3.35%) of 209
      patients receiving their first course of 5-FU and in 2 (0.73%) other patients
      (p=0.044). Based on univariate analysis, the following patient groups were at
      elevated risk of cardiotoxicity: those with preexisting cardiac disease (RR=6.83,
      p=0.0023); patients receiving calcium channel blockers (RR=4.75, p=0.014); those
      receiving nitrates (RR=9.18, p=0.007); and patients receiving concomitant
      etoposide (RR=10.32, p=0.022). Patients with underlying cardiac disease require
      close monitoring while receiving continuous infusions of 5-FU. They should be
      observed for signs and symptoms of cardiotoxicity, and vital signs should be
      measured frequently. Continued reporting of 5-FU-associated cardiotoxicity is
      necessary to identify other patients at risk.

PMID- 9250551
TI  - Prevention by calcium antagonists of profibrillatory effects of class I
      antiarrhythmic drugs in acute myocardial ischemia: study in pig heart in situ.
AB  - Class I antiarrhythmic drugs do not decrease, but increase, the risk of
      ventricular fibrillation in the ischemic myocardium. On the contrary,
      vulnerability to fibrillation related to ischemia appears to be substantially
      reduced by calcium antagonists. We assessed whether the calcium antagonist
      diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusion) could prevent the
      profibrillatory effect or even partially restore the antifibrillatory effect of a
      class I antiarrhythmic drug, flecainide (1 mg/kg bolus plus 0.04 mg/kg/min
      infusion) in the ischemic myocardium of anesthetized, open-chest pigs. Ischemia
      was obtained by completely occluding the left anterior descending coronary artery
      near its origin. Vulnerability to fibrillation was assessed by electrical
      fibrillation threshold (EFT), measured with diastolic impulses of 100 msec
      duration delivered at a rate of 180 beats/minute. Diltiazem did not oppose the
      rise in EFT induced by flecainide in the absence of ischemia (6.8 +/- 1.2 to 9.9
      +/- 0.9 mA, p<0.001). It limited the fall in EFT observed under the dual
      influence of ischemia and flecainide (4.2 +/- 0.9 vs 1.3 +/- 0.6 mA, p<0.001). By
      reducing calcium entry into myocardial fibers, diltiazem delayed ischemic
      depolarization, as evidenced by reduced shortening of the monophasic action
      potential duration from 215 +/- 7 to 200 +/- 4 msec, instead of 178 +/- 6
      (p<0.001), and reduced lengthening of intraventricular conduction time from 33 +/
      5 to 43 +/- 4 msec, instead of 53 +/- 4 (p<0.01). Therefore, diltiazem is likely
      to prevent the loss and even the reversal of the antifibrillatory properties of
      flecainide due to myocardial ischemia in dosages that do not adversely affect
      myocardial contractility or atrioventricular conduction to a large extent.

PMID- 9250552
TI  - Fentanyl pharmacokinetics in patients undergoing renal transplantation.
AB  - STUDY OBJECTIVE: To describe the pharmacokinetics of fentanyl in patients
      undergoing renal transplantation. DESIGN: Prospective. SETTING: A large
      university teaching hospital. PATIENTS: Eight patients (mean +/- SD age 35.5 +/-
      11.5 yrs, weight 73.4 +/- 24.8 kg) with end-stage renal failure receiving kidneys
      from a living relative; three patients were never dialyzed, three were receiving
      peritoneal dialysis, and two were receiving hemodialysis. INTERVENTIONS: Plasma
      was sampled before and at intervals up to 8 hours after intravenous injection of
      fentanyl 25 microg/kg before skin incision. MEASUREMENTS AND MAIN RESULTS: Mean
      +/- SD (range) preoperative values were blood urea nitrogen (BUN) 66 +/- 30 (35
      111) mg/dl; albumin 3.6 +/- 0.7 (2.6-4.5) g/dl; and triglycerides 414 +/- 352
      (156-1270) mg/dl. Elimination half-life was 382 +/- 205 minutes; volume of
      distribution for the central compartment 0.74 +/- 0.48 L/kg; volume of
      distribution at steady state (Vd(ss)) 3.1 +/- 2.0 L/kg; total body clearance 7.5
      +/- 5.1 ml x kg(-1) x min(-1). A significant inverse relationship between degree
      of azotemia and fentanyl clearance was found. The two patients with the highest
      preoperative BUNs had the lowest multiple of clearance and Vd(ss), and were also
      the only ones to require postoperative mechanical ventilation. CONCLUSION:
      Although all patients received a kidney that functioned well after
      revascularization, the large intersubject variability in fentanyl kinetics may,
      in part, reflect their heterogeneity in dialysis status and renal failure-induced
      abnormalities. Marked decreases in fentanyl clearance do occur in these patients,
      appear to be related to very high BUN concentrations, and can lead to prolonged
      postoperative ventilatory depression.

PMID- 9250553
TI  - Altered protein binding of quinidine in patients with atrial fibrillation and
      flutter.
AB  - STUDY OBJECTIVES: To determine if alpha1-acid glycoprotein (AAG) concentrations
      are altered in patients with atrial fibrillation and flutter (AFF), and to
      establish if fluctuations in AAG change the free fraction of quinidine. DESIGN:
      Prospective, controlled, nonrandomized. SETTING: Tertiary care medical center and
      outpatient clinics. PATIENTS: Thirty patients with AFF and 16 matched controls.
      INTERVENTIONS: Serial blood samples were collected from patients with AFF at
      baseline and for 28 days after cardioversion. The control group received no
      treatment and a single blood sample was obtained. MEASUREMENTS AND MAIN RESULTS:
      Concentrations of AAG were measured by Laurell-Rocket immunoelectrophoresis.
      Quinidine concentrations were determined by fluorescence polarization immunoassay
      using the Abbott TDx system. Baseline AAG concentrations in patients with AFF
      (122 +/- 55 mg/dl) were significantly increased compared with the control group
      (62 +/- 28 mg/dl, p<0.0005). Concentrations of AAG remained elevated after
      conversion to sinus rhythm and did not significantly change over the study
      period, regardless of method of cardioversion (p>0.2). In patients with AFF, the
      free fraction of quinidine at the highest AAG concentration was 8.5 +/- 2.3%.
      This was significantly reduced compared with the value in the control group (12.5
      +/- 3.0%, p<0.05) as well as that in patients with AFF at the lowest AAG
      concentration (11.0 +/- 2.5%, p<0.05). Overall at the highest AAG concentration,
      patients with AFF had a relative reduction in the quinidine free fraction by 32%
      compared with controls. Regression analysis showed an indirect relationship
      between serum AAG concentration and the unbound fraction of quinidine (r=0.56)
      CONCLUSIONS: Concentrations of AAG are increased in patients with AFF and remain
      elevated for at least 28 days after cardioversion. Elevated AAG concentrations
      significantly reduce the free fraction of quinidine.

PMID- 9250554
TI  - Antianginal response to once-daily diltiazem CD in patients receiving concomitant
      beta-blockers, long-acting nitrates, or both. Diltiazem CD Study Group.
AB  - STUDY OBJECTIVE: To determine the safety and efficacy of diltiazem CD 180 mg
      administered once/day in patients with chronic stable angina inadequately
      controlled with P-blockers, long-acting nitrates, or both. DESIGN: Multicenter,
      randomized, double-blind, placebo-controlled, parallel-group trial. SETTING:
      Medical clinics in the private and academic sectors. PATIENTS: Of 172 patients,
      170 completed the 2-week double-blind treatment period. INTERVENTION: . Patients
      received either diltiazem CD 180 mg or placebo once/day in combination with
      existing antianginal therapy. MEASUREMENTS AND MAIN RESULTS: The time to
      termination of exercise tolerance testing, 24 hours after the dose increased
      significantly in the diltiazem CD group (37.2 sec) compared with the placebo
      group (21.3 sec, p=0.0438). Time to onset of angina during exercise testing also
      increased (57.6 vs 35.0 sec, respectively, p=0.0324), as did time to moderate
      angina (37.5 vs 20.6 sec, respectively, p=0.0354). The rates of total angina
      attacks and of angina attacks on exertion were significantly reduced in the
      diltiazem CD group versus placebo (p<0.05). Significant reductions in systolic
      and diastolic blood pressures and heart rate-blood pressure product measured at
      rest, submaximum exercise, and exercise termination were observed in diltiazem CD
      treated patients compared with placebo (p<0.05). The frequency of treatment
      related adverse events was identical in the two groups, 15.1%. CONCLUSION:
      Diltiazem CD 180 mg once/day is an effective, safe, and beneficial initial dosage
      when added to existing antianginal therapy.

PMID- 9250555
TI  - Evaluation of effects of terbinafine on single oral dose pharmacokinetics and
      anticoagulant actions of warfarin in healthy volunteers.
AB  - STUDY OBJECTIVE: To evaluate the potential effects of oral terbinafine, a new
      synthetic antifungal agent of the allylamine class, on the pharmacokinetics and
      pharmacodynamics of racemic warfarin. DESIGN: Randomized, double-blind, placebo
      controlled, crossover study. SUBJECTS: Sixteen healthy men. INTERVENTIONS:
      Placebo or terbinafine 250 mg was administered once/day for 14 consecutive days,
      separated by a washout period lasting at least 2 weeks. A single oral dose of
      racemic warfarin 30 mg was coadministered with placebo or terbinafine on day 8 of
      each treatment period. Blood samples were collected for 168 hours after
      administration of warfarin to determine the drug's pharmacokinetics and
      anticoagulant effects. MEASUREMENTS AND MAIN RESULTS: No major differences were
      seen in the plasma concentration-time profiles of a single dose of warfarin
      administered with terbinafine or with placebo. CONCLUSIONS: Because of the lack
      of clinically significant interactions between terbinafine and warfarin during
      multiple-dose administration of terbinafine, no adjustment of warfarin dosage
      during concomitant therapy appears to be necessary.

PMID- 9250556
TI  - Drug interaction potential with inhibitors of HIV protease.
AB  - We conducted a retrospective chart review to estimate the potential for drug
      interactions in subjects infected with the human immunodeficiency virus-1 when a
      protease inhibitor was added to existing therapy. Medical records of 50 patients
      in each of three immunologic strata (CD4 cell counts/microl < 100, 100-199, 200
      500) were randomly selected from records of all patients receiving care at the
      clinic; 114 records were evaluable. The probabilities of one interaction or more
      were 31%, 42%, and 77% of patients if treated with indinavir, saquinavir, and
      ritonavir, respectively, across all CD4 groups; when the CD4 count was below 100
      cells/microl, the probabilities were 55%, 63%, and 93%. Many of these
      interactions, however, resulted from administration of rifabutin, a drug likely
      to decrease in importance as less toxic alternatives become more widely
      administered. The potential for drug interactions is high when starting protease
      inhibitor therapy, especially in patients with low CD4 cell counts who receive
      ritonavir. Concurrent therapy must be evaluated before treatment, as many agents
      are either contraindicated or require dosage modification.

PMID- 9250557
TI  - Recovery parameters after sevoflurane and isoflurane anesthesia.
AB  - We compared recovery times in patients with American Society of Anesthesiologists
      physical status I-III receiving sevoflurane or isoflurane during surgical
      procedures longer than 1 hour in duration. Of the 50 patients enrolled, 23
      received sevoflurane and 27 received isoflurane. Anesthetic gases were
      discontinued abruptly at the end of the surgical procedure. The following
      parameters were recorded: time to emergence (opens eyes), time to extubation,
      response to verbal command (squeezes hand of observer), and orientation (time and
      place). Exposure times to the agents were similar. The time to emergence was
      significantly less with sevoflurane than with isoflurane (5.6 vs 11.2 min,
      respectively). There were no significant differences in time to extubation,
      response to verbal command, or orientation between the groups. Our data support
      more rapid emergence with sevoflurane than with isoflurane in surgical procedures
      longer than 1 hour in duration.

PMID- 9250558
TI  - The influence of bromfenac on the pharmacokinetics and pharmacodynamic responses
      to glyburide in diabetic subjects.
AB  - STUDY OBJECTIVE: To assess the effect of bromfenac sodium, a nonnarcotic
      analgesic drug under development, on the pharmacokinetics and pharmacodynamics of
      glyburide in patients with type II diabetes. DESIGN: Randomized, double-blind,
      placebo-controlled, multiple-dose study with a two-period crossover design.
      PATIENTS: Eleven men and one woman (age 36-64 yrs) whose diabetes was responsive
      to oral sulfonylurea therapy. INTERVENTIONS: Placebo or bromfenac 50 mg was given
      as a single oral dose 3 times/day for the first 3 days of the study. On days 4-6,
      patients received the alternative treatment. For at least 3 months before and
      during the study, patients took their usual single daily dose of glyburide 10 mg.
      MEASUREMENTS AND MAIN RESULTS: Bromfenac concentrations were measured by high
      performance liquid chromatography with ultraviolet detection. Glyburide
      concentrations were measured by gas chromatography with nitrogen-phosphorus
      detection. Glycemia was measured repeatedly on day 3 of each treatment.
      Pharmacokinetic analysis was performed with noncompartmental techniques. No
      significant differences in the pharmacokinetics of glyburide or in the
      pharmacodynamic response of serum glucose levels were observed between placebo
      and bromfenac. Intersubject variability of concentrations was modest for
      glyburide and glucose, with a CV of 43% or less. CONCLUSION: Glyburide levels are
      not changed during concomitant administration of bromfenac.

PMID- 9250560
TI  - Impact of a pharmacist-based consult service on nutritional rehabilitation of
      nonambulatory patients with severe developmental disabilities.
AB  - A pharmacist consult service was developed to evaluate the appropriateness of
      enteral feeding through a permanent ostomy in 24 nonambulatory patients with
      severe developmental disabilities. Several problems with enteral nutrition were
      identified. Policies to improve them were instituted, and several educational
      presentations were made. Pharmacists' actions were implemented, including
      assessment of energy needs by indirect calorimetry and rearrangement of enteral
      feeding schedules to achieve optimal nutrition support and pharmacotherapy
      administration. By the fourth month of the consult service, body weight in these
      patients increased from 101 +/- 6% of baseline to 109 +/- 7% (p<0.05). Weight
      continued to increase through the seventh month of the consult service to 116 +/-
      12% of baseline (p<0.0001). Measured resting energy expenditure for the group was
      889 +/- 170 kcal/day compared with the predicted 1055 +/- 163 kcal/day.

PMID- 9250559
TI  - Effects of terbinafine on the pharmacokinetics of digoxin in healthy volunteers.
AB  - STUDY OBJECTIVE: To assess the potential effects of terbinafine, a new synthetic
      allylamine antifungal agent, on the pharmacokinetics of a single 0.75-mg oral
      dose of digoxin. DESIGN: Randomized, double-blind, placebo-controlled, crossover
      study consisting of two treatment periods. SUBJECTS: Sixteen healthy men and
      women volunteers. INTERVENTIONS: During treatment A, placebo was administered
      once/day for 12 days; during treatment B, terbinafine 250 mg was administered
      orally once/day for 12 days. The washout period between treatments was at least 2
      weeks. A single 0.75-mg oral dose of digoxin was administered on day 8 of each
      period. Blood samples were collected after administration of digoxin to determine
      pharmacokinetics. MEASUREMENTS AND MAIN RESULTS: Compared with placebo,
      terbinafine did not alter the time course of the digoxin serum levels. Although
      the time to maximum peak concentration with terbinafine was slightly reduced, the
      maximum concentration and area under the serum drug concentration-time curve from
      time zero to 120 hours were not significantly different with terbinafine than
      with placebo. No drug-related side effects were reported with either active
      treatment, and no clinically significant changes in vital signs, physical
      examination results, electrocardiograms, or clinical laboratory results were
      observed. CONCLUSIONS: No special dosage adjustments for digoxin appear to be
      necessary during concomitant therapy with terbinafine.

PMID- 9250561
TI  - Pharmacist's management of drug-related problems: a tool for teaching and
      providing pharmaceutical care.
AB  - During the development of education and practice models based on the philosophy
      of pharmaceutical care (PC), six pharmacists worked with the University of
      Toronto Faculty of Pharmacy to implement the PC model in their practice sites.
      These pharmacists found it necessary to modify existing tools to create one that
      explicitly guided them through the PC process, including the phase of monitoring
      patients for desired outcomes. This resulted in the development of the
      Pharmacist's Management of Drug Related Problems. This tool requires pharmacists
      to collect patient drug and medical data and write responses to specific
      questions about the data to interpret their significance. As proficiency in
      providing PC is attained, the questions and space for written responses can be
      eliminated, leaving a comprehensive documentation system of patient outcomes and
      the data collected, recommendations made, and monitoring completed by the
      pharmacist. This tool has been adopted by the University of Toronto Faculty of
      Pharmacy and is being used in various continuing education programs and by
      practicing pharmacists across Canada.

PMID- 9250562
TI  - Pharmacoeconomic impact of once-daily aminoglycoside administration.
AB  - A retrospective cost analysis compared hospital costs of standard gentamicin
      dosing and once-daily regimens in 1127 patients. Hospital costs compared were
      drug/supply/preparation/administration (DSPA; $4.56/500 mg once-daily dose and
      $3.32/100 mg every 8 hrs standard dose); therapeutic drug monitoring (TDM)
      ($25/gentamicin level); and nephrotoxicity management. The mean length of therapy
      was 4.5 days with both regimens. The mean number of blood samples drawn to
      measure drug levels was 0.65 for once-daily dosing and 1.7 for standard dosing.
      Mean DSPA and TDM costs/patient for a 4.5-day course of once-daily therapy were
      $20.52 and $16.25, respectively ($36.77/course of therapy). In comparison,
      estimated mean DSPA and TDM costs for 4.5 days standard therapy were $44.82 and
      $42.50, respectively ($87.32/course of therapy). We observed an overall reduction
      in nephrotoxicity from approximately 4% to 1.2% with the once-daily program,
      resulting in a nephrotoxicity management cost reduction from $182 to $55/patient
      exposed to aminoglycosides. The once-daily program resulted in a 58% reduction in
      aminoglycoside-associated hospital cost and a nephrotoxicity management savings
      of 70%/patient.

PMID- 9250563
TI  - Azathioprine-induced multisystem organ failure and cardiogenic shock.
AB  - Azathioprine is administered to treat increasing numbers of disorders over a wide
      range of organ systems. The potential for the drug to cause widespread organ
      dysfunction is not fully appreciated. In fact, azathioprine can cause multisystem
      organ dysfunction involving the kidneys, liver, and cardiovascular system. The
      discovery of global cardiac dysfunction as one component of this complication may
      indicate a mechanism of hypotension. Clinicians must be aware of the potential
      for azathioprine to cause such toxicities to facilitate appropriate patient
      management.

PMID- 9250564
TI  - Ticlopidine-induced elevated liver enzymes.
AB  - Ticlopidine is a reasonable alternative to prevent stroke and myocardial
      infarction when aspirin is intolerable or ineffective. It can be limited,
      however, by its severe adverse effect profile. The most worrisome of these is
      neutropenia, although clinicians must be mindful of other adverse events that may
      be caused by this drug. A patient experienced elevated liver function tests
      probably due to ticlopidine.

PMID- 9250565
TI  - Precipitous fall in platelet count with anagrelide: case report and critique of
      dosing recommendations.
AB  - Thrombotic and hemorrhagic events may result from high circulating concentrations
      of platelets (> 1,000,000/mm3), and measures to reduce the platelet count are
      indicated in symptomatic or extreme thrombocytosis. The platelet count can be
      decreased quickly by plasmapheresis, but the effect is transient. Patients with
      thrombocytosis secondary to a myeloproliferative disease, such as chronic
      myelogenous leukemia (CML), frequently require more sustained suppression of the
      platelet count. Hydroxyurea, busulfan, and interferon are used to maintain a
      lower platelet count but are occasionally ineffective or intolerable. An
      alternative to these therapies is anagrelide, a quinazolin derivative that was
      approved by the Food and Drug Administration in March 1997. Because current
      dosing guidelines for anagrelide are scarce, the dosing method of the Anagrelide
      Study Group that published the largest study to date on the drug's efficacy in
      thrombocytosis was followed. Two unexpected episodes of anagrelide-induced
      thrombocytopenia occurred despite following these dosing methods. This prompted a
      critical evaluation of the pharmacodynamic response and the appropriateness of
      anagrelide dosage recommendations. A case of thrombocytosis treated with
      anagrelide in a patient with CML is described.

PMID- 9250566
TI  - Reduced serum theophylline concentrations after discontinuation of azithromycin:
      evidence for an unusual interaction.
AB  - A 68-year-old man receiving long-term therapy with oral sustained-release
      theophylline 450 mg twice/day was admitted to the hospital after failing
      treatment with azithromycin for an acute exacerbation of obstructive lung
      disease. Peak serum theophylline concentration was 20 microg/ml (normal 10-20
      microg/ml). Azithromycin was discontinued and the theophylline dosage reduced by
      33%. The subsequent 80% decrease in serum theophylline to 4.6 microg/ml was
      unexpectedly large. Two rechallenges produced similar transient depressions of
      serum theophylline concentrations after withdrawal of azithromycin, suggesting an
      interaction. Withdrawal of azithromycin may leave an increased number of active
      enzyme sites available as the drug is cleared from the system. In some
      circumstances, it may be useful for pharmacokinetic interaction studies to
      continue measuring concentrations after the suspected interacting agent is
      stopped.

PMID- 9250567
TI  - Torsades de pointes with administration of high-dose intravenous d-sotalol to a
      patient with congestive heart failure.
AB  - A patient with heart failure was administered d-sotalol 3.0 mg/kg infused over 2
      minutes. The patient had normal electrolytes and baseline QT. Six minutes after
      drug administration the QT prolonged to 600 msec, and the patient developed
      torsades de pointes and required electrical cardioversion. This emphasizes the
      need to consider both rate of administration and the dosage when evaluating the
      safety and efficacy of a new class III antiarrhythmic drug.

PMID- 9250568
TI  - Removal of phenobarbital during continuous cycling peritoneal dialysis in a
      child.
AB  - A 2.5-year-old child receiving phenobarbital for a history of seizures while on
      continuous cycling peritoneal dialysis (CCPD) had persistent subtherapeutic serum
      levels despite progressive dosage increases. Phenobarbital concentration was
      measured in the peritoneal dialysate effluent and peritoneal clearance was
      calculated. Thirty-five percent of the total phenobarbital daily dose was being
      removed through 24-hour CCPD. Our findings were consistent with previous reports
      of 40% and 50% phenobarbital removal during continuous ambulatory peritoneal
      dialysis and acute peritoneal dialysis, respectively. In addition, phenobarbital
      clearance was greater during the period when more exchanges were done compared
      with the period when patient went through one cycle with a longer dwell time.
      Based on these preliminary data, it seems that larger dosages of phenobarbital
      are necessary in patients undergoing continuous peritoneal dialysis, and that the
      amount removed can differ significantly depending on the number of cycles.

PMID- 9250569
TI  - A prospective, open-label study of single-dose ciprofloxacin absorption after
      chemotherapy in patients with malignancy.
AB  - The absorption of a single oral dose of ciprofloxacin 750 mg in patients with
      cancer who had chemotherapy-induced Cancer and Leukemia Group B grade I or II
      mucositis was evaluated. Ciprofloxacin was administered after an overnight fast.
      Plasma samples were collected before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours
      after the dose. Drug concentrations were determined by reverse-phase high
      performance liquid chromatography with fluorescence detection. Pharmacokinetic
      values were characterized by noncompartmental methods. The mean +/- SD for area
      under the curve, mean peak concentration (C(max)), and time to C(max) (T(max))
      were 18.7 +/- 5.03 mg/L x hour, 4.41 +/- 1.74 mg/L, and 1.81 +/- 0.843 hours,
      respectively. The absorption of oral ciprofloxacin in patients with chemotherapy
      induced grade I or II mucositis compares with that in healthy volunteers. These
      findings may call for further pharmacokinetic evaluation of the drug in a similar
      patient population.

PMID- 9250570
TI  - Integrated pharmaceutical care services: the product is part of the care.

PMID- 9250571
TI  - Implementing pharmaceutical care: do we understand its implications?

PMID- 9250572
TI  - Dihydropyrimidine dehydrogenase deficiency: a potential etiology for 5
      fluorouracil-induced neurotoxicity.

PMID- 9250573
TI  - Validity of the GUSTO trial's main conclusion. Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronaries.

PMID- 9250574
TI  - Comparison of two formulations of nifedipine during 24-hour ambulatory blood
      pressure monitoring--a comment.

PMID- 9250576
TI  - Inhibitory effects of pituitary adenylate cyclase activating polypeptide on
      histamine-induced respiratory resistance in anesthetized guinea pigs.
AB  - Asthma is a chronic inflammatory disorder of the airways in which many cells
      participate. This inflammation causes recurrent episodes and symptoms that are
      associated with widespread but variable airflow limitation that is at least
      partly reversible either spontaneously or with treatment. Therefore, an
      investigation of useful remedies for the treatment of bronchial asthma is
      proposed. In this study, we determined whether both forms of pituitary adenylate
      cyclase activating polypeptide (PACAP 38 and PACAP 27) belonging to the
      vasoactive intestinal peptide (VIP) family of peptides could inhibit the effects
      of histamine-induced respiratory resistance (Rr) in anesthetized guinea pigs,
      when compared with VIP. The order for 50% suppression (ED50) of Rr induced by
      peptides was VIP > PACAP 27 > PACAP 38. The inhibitory effects induced by PACAP
      38 on histamine-induced Rr in guinea pigs were more prolonged than with the other
      two peptides. Moreover, adding the endopeptidase inhibitor phosphoramidon
      prolonged the inhibitory effects of PACAPs. These results suggested that the
      exogenous peptides of the inhibitory nonadrenergic noncholinergic nervous (i
      NANC) peptides could become a useful remedy for treatment of bronchial asthma,
      because these belong to an important intrinsic hormone.

PMID- 9250575
TI  - Involvement of prostaglandins and CGRP-dependent sensory afferents in peritoneal
      irritation-induced visceral pain.
AB  - This study investigates the contribution of prostaglandins (PG) and calcitonin
      gene-related peptide (CGRP) pathways in visceral pain induced by peritoneal
      irritation in rats. Peritoneal irritation was produced by i.p. administration of
      acetic acid (AA: 0.06-1.0%, 10 ml/kg). Visceral pain was scored by counting
      abdominal contractions. The effect of CGRP (3-100 microg/kg, i.p.) was also
      evaluated. Like AA, CGRP induced abdominal pain. Neonatal pretreatment with
      capsaicin reduced abdominal contractions produced by AA (0.6%) and CGRP (20
      microg/kg) with 64.6% and 45.6%, respectively. Abdominal contractions induced by
      AA and CGRP were blocked by two antinociceptive drugs, mu-and kappa-opioid
      agonists, morphine and (+/-)-U-50,488H, respectively. Indomethacin (3 mg/kg,
      s.c.) reduced the number of abdominal contractions produced by AA by 78.1%+/-6.4%
      but did not inhibit abdominal contractions produced by CGRP. The CGRP, receptor
      antagonist, hCGRP(8-37) (300 microg/kg, i.v.) inhibited AA- and CGRP-induced
      abdominal contractions with 57.5%+/-12.4% and 51.6%+/-11.3%, respectively.
      Concomitant i.p. administration of PGE1 and PGE2 (0.3 mg/kg of each) produced
      abdominal contractions which were inhibited 45.6%+/-9.3% by hCGRP(8-37) (300
      microg/kg i.v.). Taken together, these results suggest that peritoneal irritation
      is likely to trigger the release of prostaglandins, which in turn produces a
      release of CGRP from primary sensory afferents.

PMID- 9250577
TI  - Immunohistochemical localization of type-II (AT2) angiotensin receptors with a
      polyclonal antibody against a peptide from the C-terminal tail.
AB  - A polyclonal antibody has been prepared against a synthetic peptide derived from
      the C-terminal tail of the cloned rat AT2 angiotensin receptor, corresponding to
      amino acid residue 341-351. The antibody was of high titer and displayed
      monospecific activity toward the synthetic peptide in the ELISA assay. Western
      blot analysis indicated that the antiserum recognised only a single protein band
      with a mean apparent molecular mass of 75.4 kDa in the rat adrenals.
      Immunohistochemical studies with affinity purified antibody localised
      immunoreactive AT2 angiotensin receptor in medulla cells of the adrenals.
      Immunoreactivity was also observed in pyramidal tract, but no specific
      immunoreactivity can be detected in regions of rat brain that are known to
      express AT2 angiotensin receptors, including inferior olive, locus coeruleus and
      cerebellum.

PMID- 9250578
TI  - Pharmacological characterisation of oxytocin binding sites in the ovine pineal
      gland.
AB  - Both oxytocin (OT) and [Arg8]vasopressin (AVP) are found within the ovine pineal
      gland and may function to modulate melatonin secretion. However, the receptors
      which mediate the actions of these peptides have yet to be characterised.
      Preliminary studies of ovine pineal microsomal cell membranes showed binding of
      [3H]OT (79+/-9 fmol/mg) 10 times greater than binding of [3H]AVP (8+/-3 fmol/mg).
      Saturation studies using either [3H]OT or the selective OT receptor ligand
      [125I]d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)]-vasotocin (OTA) revealed high
      affinity, single site kinetics (Kd = 1.72+/-0.32 nM; Bmax = 68+/-18 fmol/mg).
      Binding of [3H]AVP was more effectively displaced by OT than AVP, suggesting that
      binding may be due to cross-reaction with the OT binding site. Displacement of
      [3H]OT using a range of selective agonists and antagonist analogues revealed
      pharmacological characteristics similar to [3H]OT binding sites in the ovine and
      rat uterus. These data show that the ovine pineal expresses a high density of OT
      binding sites which may participate in the regulation of melatonin secretion.

PMID- 9250579
TI  - Vasoactive intestinal peptide supports induced migration of human keratinocytes
      and their colonization of an artificial polyurethane matrix.
AB  - We investigated the effect of the neuropeptides vasoactive intestinal peptide
      (VIP), (D-Phe2)-VIP, (Lys-Pro-Arg-Tyr)-VIP and the VIP fragment (1-12) on induced
      migration and colonization in vitro. In confluent keratinocyte cultures "wounded"
      with a razor blade, the VIP-treated samples disclosed a more rapid migration from
      the wound margins into the wound bed, starting within the first 4 h. Almost 80%
      of the wounded area was covered within 24 h. In contrast, VIP-derivatives were
      not significantly different from controls, covering 10 to 18% of the wounded area
      (p < 0.02). Colonization has been assessed with an artificial non-toxic
      polyurethane matrix. In controls, we were able to observe migration of
      keratinocytes on the matrix within the first 24 h. The cells, however, were not
      able to migrate further and to survive. After 48 h, VIP-treated cultures showed a
      complete colonization of the matrix by keratinocytes vs. less than 10% of the
      total area in controls (p < 0.001). The induction of migration and of
      colonization was VIP-dose-dependent. The data indicate that induced migration is
      stimulated by VIP, when the N-terminal ending is intact, but loss of the C
      terminus abrogates both migration and colonization. Our investigations have
      implications for wound healing but also for bioengineering of skin.

PMID- 9250580
TI  - Immunoreactivity for the alpha-subunit of the pituitary glycoprotein hormones in
      pulmonary neuroendocrine cells of developing human lung and various perinatal
      diseases.
AB  - Infant lung tissue, obtained at autopsy, was studied by immunohistochemistry for
      the presence of pituitary glycoprotein hormones (PGHs) in the lung. The infants,
      born at term or preterm, died of various causes. The results provide the first
      immunological evidence of the presence of the common a-subunit of the pituitary
      glycoprotein hormones (alphaPGH) in the lung. The immunoreactivity is located in
      the pulmonary neuroendocrine cells and neuroepithelial bodies. In addition, the
      cells labelled by alphaPGH antisera (alphaPGH cells) form a subpopulation of the
      neuroendocrine cells detected by anti-calcitonin immunohistochemistry (CT cells).
      Moreover, the number of alphaPGH cells appears to increase after neonatal
      pneumonia or when the number of CT cells is elevated following the development of
      disease. Also, the weak staining of one of the monoclonal antibodies against the
      specific b-subunit of thyrotropin (TSH) might, in combination with the increased
      detectability of a-subunits, indicate that TSH can be endogenously produced in
      the lung.

PMID- 9250581
TI  - Hexarelin, a novel GHRP-6 analog, stimulates growth hormone (GH) release in a GH
      secreting rat cell line (GH1) insensitive to GH-releasing hormone.
AB  - Previous studies demonstrated that GHRP-6 has modest GH-releasing activity in
      primary pituitary cell monolayer cultures. However, the effects of this peptide
      have always been tested on cells very sensitive to GHRH. We have previously
      reported that GHRH is unable to stimulate GH secretion in the GH1 rat tumor cell
      line. The aim of the study was to assess for the first time the effect on GH
      secretion of the GHRP-6 analog, hexarelin, in the GH1 cells; moreover, we
      investigated the potential involvement of GHRH in the effects of hexarelin in the
      GH1 rat cell line. The GHRP-6 analog hexarelin (0.01-1 microM) significantly
      stimulated GH release in both normal and GH1 rat cells. The greatest GH-releasing
      effect of hexarelin was observed with the 1 microM dose both in GH1 (155+/-25%
      vs. control wells) and in normal rat pituitary cells (185+/-23% vs. control
      wells). GHRH significantly stimulated GH secretion in normal rat somatotrophs (3
      fold increase). In this latter cell model, GHRH and hexarelin were demonstrated
      to have additive stimulatory effects on GH secretion. Conversely, GHRH did not
      affect hexarelin-stimulated GH release in GH1 cells at any of the doses used.
      Finally, 8Br-cAMP significantly stimulated GH secretion in both normal rat and
      GH1 cells. These results provide in vitro evidence that non-GHRH-mediated
      pathways for GHRP action exist. Moreover, the observation that cells not
      sensitive to GHRH can be significantly stimulated by hexarelin strongly suggests
      that GHRPs and GHRH have two distinct sites and modes of action at the pituitary
      level.

PMID- 9250582
TI  - The characterization, localization and regulation of endothelin in ovine pars
      intermedia.
AB  - The pituitary intermediate lobe (IL) contains a single population of cells and
      has recently been shown to express endothelin (ET)-like peptides. The IL thus
      provides an excellent in vivo model to study regulation, function and processing
      of ET in an endocrine cell. The primary aims of the present study were to locate
      and characterize the precise molecular forms of ET in the ovine IL and determine
      if levels and/or processing of ET is under dopaminergic or other influences. We
      have developed a radioimmunoassay (RIA) that detects each form of ET and, when
      combined with reverse phase-HPLC (RP-HPLC), shows the ovine IL to contain
      predominantly the ET-1 isoform. In addition, using a specific anti-endothelin
      antiserum for immunohistochemistry (IHC), we localized ET-1 with alpha-melanocyte
      stimulating hormone (alpha-MSH) within the melanotroph. The effects of dopamine
      agonists, antagonists and hypothalamo-pituitary disconnection (HPD) on both
      tissue levels and processing of ET in the ovine IL were also examined. Normal
      sheep were treated chronically with haloperidol or bromocriptine to investigate
      the possibility of dopaminergic regulation of ET in the IL. In the haloperidol
      treated group, plasma prolactin levels did not vary significantly from day 0 to
      day 8, but the bromocriptine treatment reduced prolactin levels (t = 9.4 P <
      0.01). Neither bromocriptine nor haloperidol, however, affected tissue ET peptide
      levels or forms. After HPD, the HPLC profile of pooled IL showed that ET-1 levels
      in the IL are slightly increased with no change in molecular forms.

PMID- 9250583
TI  - Elevated levels of natriuretic peptides in lungs of hamsters with genetic
      cardiomyopathy.
AB  - Various alterations in the natriuretic peptide system have been observed in heart
      and plasma in humans and animals with heart failure. However, there is limited
      information about these hormones in hamster lung especially in those with genetic
      cardiomyopathy, a model of human congestive heart failure. Therefore, the aim of
      the present study was to investigate the content of the three natriuretic
      peptides (atrial natriuretic peptide (ANP); brain natriuretic peptide (BNP); C
      type natriuretic peptide (CNP) and their gene expression in lungs of normal and
      cardiomyopathic hamsters. The presence of mRNA coding for ANP and BNP in lungs
      and heart was investigated by Northern blot and confirmed by reverse
      transcription polymerase chain reaction (RT-PCR). The peptide contents and plasma
      concentrations were determined by specific radioimmunoassays. Plasma ANP
      increased in hamsters with moderate to severe cardiomyopathy (aged 230 days) from
      control levels of 71.8+/-15.8 to 243.1+/-44.0 pg/ml (P < 0.01). Plasma BNP also
      increased from 79.7+/-23.5 to 227.9+/-51.6 pg/ml (P < 0.01). The levels of the
      three peptides in lungs of 30- and 120-day-old cardiomyopathic (CMO) hamsters
      were not different from their corresponding age-matched controls. However, lung
      ANP increased in 230-day-old CMO from 589+/-63 to 1624+/-219 pg/mg protein (P <
      0.01). Lung BNP and CNP also increased from 332+/-35 to 531+/-55 pg/mg protein (P
      < 0.01) and from 118+/-21 to 224+/-29 pg/mg protein (P < 0.01), respectively.
      Lung ANP mRNA and BNP mRNA were significantly (P < 0.05) higher in 230-day-old
      hamsters than those detected in age-matched normal controls. Our data demonstrate
      that the hamster lungs produce ANP, BNP and CNP, and that this production is
      enhanced in moderate to severe cardiomyopathy. These findings imply that the lung
      natriuretic peptide system may participate in pulmonary function especially
      during cardiac dysfunction.

PMID- 9250585
TI  - Modulation of protective and pathological immunity in mycobacterial infections.
AB  - Mycobacterial infections represent major problems to global health care.
      Tuberculosis is feared particularly because of its high mortality rates whereas
      in leprosy the occurrence of immunopathology, particularly nerve damage, is a
      major problem since the bacillus itself is relatively harmless. Thus, both
      effective vaccination strategies as well as novel immunomodulating regimens are
      warranted for the control of morbidity and mortality in mycobacterial diseases.
      Since CD4+ Th1 cells and type-1 cytokines play a key role both in protective
      immunity and immunopathology in mycobacterial infections, we here describe new
      pharmacological and cytokine-based strategies to regulate Th1 immunity.

PMID- 9250584
TI  - Functional role of CD40 and its ligand.
AB  - CD40, a cell surface receptor which belongs to the TNF-R family, was first
      identified and functionally characterized on B lymphocytes. In recent years, CD40
      has been found expressed on other cells, including monocytes, dendritic cells,
      endothelial cells and epithelial cells and is now thought to play a more general
      role in immune regulation. The present paper reviews recent developments about
      CD40, with main emphasis on: (1) structure and expression of CD40 and its ligand;
      (2) CD40 signal transduction; (3) in vitro function of CD40 on different cell
      types, and (4) in vivo functions of CD40/CD40L interactions.

PMID- 9250586
TI  - Molecular cloning of caprine IL-6 cDNA and its expression in insect cells.
AB  - To analyze the interactions among immunoneuroendocrinological systems in a
      miniature Shiba goat, we attempted to clone and express caprine cDNA-encoding
      interleukin-6 (IL-6) which is well-known to exert a variety of effects on
      neuroendocrinological functions in small experimental animals. The cDNA-encoding
      caprine IL-6 was molecularly cloned from a lipopolysaccharide-stimulated adherent
      splenocyte library by the reverse transcription-polymerase chain reaction. The
      sequence analysis shows that the cloned caprine IL-6 cDNA encodes a precursor
      protein of 208 amino acids that is processed to mature protein of 180 amino acids
      with a predicted molecular weight of 20,524. The amino acid sequence of caprine
      IL-6 displays 97.8 and 51.1% degree of homology with ovine and human equivalents,
      respectively. A recombinant baculovirus containing the caprine IL-6 cDNA was
      shown to induce insect cells to efficiently secrete caprine IL-6 into culture
      supernatant up to 10(5) U/ml, as confirmed by Western blot analysis and bioassay
      with an IL-6-dependent cell line.

PMID- 9250587
TI  - Molecular cloning and expression of cynomolgus monkey interleukin-2 cDNA by the
      recombinant baculovirus system.
AB  - The cDNA encoding interleukin-2 (IL-2) of cynomolgus monkey was molecularly
      cloned from concanavalin-A-stimulated peripheral lymphocyte cDNA by the reverse
      transcription-polymerase chain reaction method. Cynomolgus monkey IL-2 cDNA
      displays a high degree of homology with the human equivalent both at nucleic acid
      (98%) and amino acid (96%) sequence levels, although having only one additional
      amino acid residue. Recombinant monkey IL-2 secreted by insect cells infected
      with the recombinant baculovirus migrated as two distinct bands with 15 and 18 kD
      corresponding to mature and precursor IL-2 molecules, respectively, which were
      revealed to cross-react with anti-human IL-2 polyclonal antibody in Western blot
      analysis. This monkey IL-2 exhibited high biological activity up to an order of
      10(6) U/ml as assessed by an IL-2-dependent cell proliferation assay and was
      shown to be neutralized by anti-human IL-2 antibody.

PMID- 9250588
TI  - Oral immunization with poly-(D,L-lactide-co-glycolide) and poly-(L-lactic acid)
      microspheres containing pneumotropic bacterial antigens.
AB  - Encouraged by recent findings showing the usefulness of nonreplicating antigen
      delivery systems in the induction ofmucosal immune responses, we investigated
      microspheres as a means to deliver LW 50020, an immunomodulator consisting of
      lysates of seven common respiratory pathogens. BALB/c mice were orally immunized
      with LW 50020 encapsulated into poly-(D,L-lactide-co-glycolide) (PLG) and poly-(L
      lactic acid) (PLA) microspheres prepared by either a solvent-evaporation or a
      solvent-extraction double-emulsion technique. Particle uptake into intestinal
      Peyer's patches, induction of antibodies in sera and secretion of immunoglobulins
      by isolated Peyer's patches, lungs and spleen lymphocytes were investigated. Our
      results revealed size and surface characteristic-dependent uptake of microspheres
      into Peyer's patches. Microsphere translocation into Peyer's patches was
      efficient for 0.8-microm microspheres, but poor for 2.0-microm and surface
      modified microspheres. We showed an enhanced immune response in the lungs and
      sera following oral immunization with 0.8-microm PLG solvent-evaporation
      microspheres. The immunomodulation was statistically significant as compared to
      free LW 50020. In contrast, oral immunization with other preparations caused
      reduced or absent modulation of the immune response compared to 0.8-microm
      microspheres and free antigen. These findings indicate that microspheres
      displaying small particle sizes, rapid antigen release and high antigen content
      provide optimal tools to deliver orally applied antigens.

PMID- 9250589
TI  - Murine silver-induced autoimmunity: silver shares induction of antinucleolar
      antibodies with mercury, but causes less activation of the immune system.
AB  - BACKGROUND: Mercury and silver induce antinucleolar autoantibodies (ANoA)
      targeting the 34-kDa nucleolar protein fibrillarin in susceptible mouse strains.
      Mercury has the ability to cause a general activation of the immune system, but
      antigen-specific mechanisms following direct or indirect interaction between
      mercury and fibrillarin are now believed to play a crucial role in the autoimmune
      pathogenesis. Our previous studies showed that silver neither induced the
      systemic immune complex deposits nor the increase of serum immunoglobulins seen
      after mercury treatment. The main objective of this study was to examine the
      relation between activation of the immune system and the induction of ANoA.
      METHODS: During 4 weeks of subcutaneous silver nitrate injections into mice of
      the susceptible A.SW and SJL strains and the resistant A.TL strain, the number of
      T and B cells as well as the expression of cell surface activation and
      proliferation markers were monitored by flow cytometry. The number of cytoplasmic
      Ig+ splenocytes was determined by direct immunofluorescence technique on slides,
      and serum Ig levels as well as anti-ssDNA anti anti-DNP antibodies were
      determined by ELISA. Serum ANoA were monitored by the indirect immunofluorescence
      technique. RESULTS: Silver caused in the susceptible strains a weaker and later
      activation and proliferation of T and B cells than mercury, and no significant
      polyclonal B cell activation. In contrast, the ANoA titer was not different from
      that seen in mercury-treated mice of the same strains. Silver-treated mice of the
      A.TL strain showed neither activation of the immune system nor ANoA. CONCLUSIONS:
      Despite being as effective as mercury inducing ANoA, silver caused only a slight
      activation of the immune system. This demonstrates that the massive activation of
      the immune system in mercury treatment is not necessary for the induction of
      ANoA, and indicates that (auto)antigen-specific mechanisms are likely to play a
      key role in mercury- and silver-induced murine autoimmunity.

PMID- 9250590
TI  - Characterization of Fc epsilonRI expressing human monocytic cell lines. 1. The
      role of CD45 on signal transduction in primary monocytes and cell lines.
AB  - BACKGROUND: Recently, the high affinity receptor for IgE (Fc epsilonRI), which
      plays a major role in allergies, has been identified on a number of different
      antigen-presenting cell types, including human monocytes from atopic and
      nonatopic donors. In this report human monocytic cell lines were used to test for
      the expression of Fc epsilonRI, reasoning that a monocytic cell line expressing
      Fc epsilonRI constitutively would be a useful tool for large scale studies on the
      regulation of IgE binding and signal transduction. METHODS: Reverse transduction
      polymerase chain reaction was applied to identify Fc epsilonRI alpha-chain
      message, flow cytometry to detect Fc epsilonRI surface expression and signal
      transduction on the cell lines generated by transfection. RESULTS: We report the
      establishment of monocytic cell lines constitutively expressing Fc epsilonRI
      (THP1-alpha01 to THP1-alpha40) generated by transfection of the cell line THP1
      with a plasmid encoding the Fc epsilonRI alpha-chain only. Fc epsilonRI on the
      THP1-alpha lines specifically binds IgE and is functional with regard to ligand
      binding and signal transduction. Comparative studies between the transfectants
      and primary human monocytes from nonatopic donors demonstrated the regulatory
      role of the tyrosine phosphatase CD45 on Fc epsilonRI-mediated cell activation.
      CONCLUSIONS: Monocytic cell lines carry Fc epsilonRI alpha-chain RNA and
      enhancement by transfection results in surface Fc epsilonRI expression on THP1.
      Triggering the receptor on the THP1-alpha lines or on human monocytes, which
      express native Fc epsilonRI, elicits a rapid and transient calcium mobilization,
      prevented by co-cross-linking of Fc epsilonRI and CD45.

PMID- 9250592
TI  - Specific binding sites for 1-O-alkyl-sn-glyceryl-3-phosphorylcholine on intact
      human blood neutrophils.
AB  - Infection, inflammation and allergy are characterized by an infiltration of
      neutrophils or eosinophils in the tissue and are associated with an increased
      level of lysophospholipids. In this study it is shown that labeled 1-O-alkyl-sn
      glyceryl-3-phosphorylcholine (lyso-paf) binds to intact human blood neutrophils.
      Unlabeled lyso-paf(500 nM) inhibits the binding of [3H]lyso-paf to neutrophils in
      the presence of fatty acid-free serum albumin (0.25%). A linear Scatchard plot
      analysis of the specific [3H]lyso-paf binding to neutrophils revealed a KD value
      of 9.2 nM with 4,100 lyso-paf binding sites per neutrophil at 4 degrees C. Lyso
      paf increased the specific binding of labeled platelet-activating factor
      ([3H]paf) to neutrophils at 20 degrees C. The increased specific binding of
      labeled paf to neutrophils could only be demonstrated when sterile cell
      preparation methods were used. Intact human blood eosinophils did not express
      specific lyso-paf binding sites. These results suggest that the lyso-paf binding
      sites on neutrophils have an up-regulatory function for paf which might be
      involved in neutrophil-mediated disorders.

PMID- 9250591
TI  - A novel antifolate, MX-68, inhibits the development of autoimmune disease in
      MRL/lpr mice.
AB  - We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable
      antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease
      which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral
      administration of either MX-68 or MTX was commenced in 8-week-old female mice and
      continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the
      onset of proteinuria and prolonged life span dose-dependently. Furthermore, it
      suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX
      68 was as effective as MTX at ameliorating events which accompany the development
      of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These
      ameliorative effects of MX-68 and MTX did not occur via inhibition of either
      autoantibody production or cell proliferation. Neither compound suppressed age
      dependent elevation of immune complexes or antibodies for single-stranded DNA and
      TNP in serum nor did they influence the associated enlargement of lymph nodes and
      spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune
      kidney disease in mice and may be useful for other related diseases such as
      systemic lupus erythematosus.

PMID- 9250593
TI  - Vesicular transport of Charcot-Leyden crystal protein in f-Met peptide-stimulated
      human basophils.
AB  - The ultrastructural localization of Charcot-Leyden crystal (CLC) protein during f
      Met-peptide-induced degranulation of human basophils was analyzed at multiple
      times after stimulation. In this secretion model, piecemeal and anaphylactic
      degranulation occurred sequentially in stimulated cells and were followed by
      reconstitution of granule contents. This analysis showed that granule number and
      alteration and location of gold-labeled, formed CLCs changed over time. CLCs were
      extruded from granules and remained attached to plasma membranes early after
      stimulation. At later times, similar structures reappeared in granules in
      quantity. Smooth-membrane-bound vesicles, analyzed by number, by visible particle
      contents (or lack of contents) and by gold labeling for CLC protein, showed that
      empty vesicles increased at the earliest time sampled (0 time) and plunged
      thereafter in actively extruding and completely degranulated cells. Vesicles
      containing granule particles were elevated initially at 10 s and at later times.
      Gold-labeled CLC-protein-containing vesicles were of either empty or particle
      filled varieties, and both types were involved with CLC protein transport out of
      cells at early times and into cells at later times as basophils recovered. Thus,
      vesicle transport of CLC protein is a mechanism for producing piecemeal
      degranulation and endocytotic recovery of released CLC protein from human
      basophils. This vesicular shuttle may be an effector mechanism for widespread
      piecemeal losses from granules in basophils in inflammatory sites in vivo in
      human disease.

PMID- 9250595
TI  - IgE responsiveness to Dermatophagoides farinae in asthma and atopic dermatitis.
AB  - Using Western blotting and RAST, this study examined IgE reactivities to
      Dermatophagoides farinae (Df) extract in three groups of children with either
      asthma, atopic dermatitis (AD) or a combination of both. The Df antigen presented
      at least nine distinct IgE-binding bands, with apparent molecular weights of 15,
      25, 30, 40, 48, 59, 67, 80 and 110 kD. Positive IgE binding reactions to 15-kD
      proteins were found in more than 85% of subjects in all three groups, and
      positive reactions to 25-, 30- and 110-kD proteins in 35-45% in each group. The
      frequencies of positive IgE binding reaction to other components were generally
      low in all three groups. The pattern of IgE reactivity to Df components did not
      differ significantly between the three groups of subjects. IgE-binding activities
      to two major allergens, Der f1 and Der f2, were also examined by RAST, using
      recombinant antigens. High RAST reactivities to Der f1 and Der f2 were found in
      three groups, and the average RAST levels for Der f1 and Der f2 did not differ
      significantly between the three groups. These findings suggest that a difference
      in IgE responsiveness to house dust mite antigen is not a major discriminative
      factor in determining the difference between asthma and AD.

PMID- 9250594
TI  - Human IgE binding capacity of tryptic peptides from bovine alpha-lactalbumin.
AB  - The specific IgE binding capacity of native bovine alpha-lactalbumin (alpha-La),
      a globular whey protein, and tryptic peptides was investigated using 19 sera from
      patients with cow's milk protein allergy. The specific anti-bovine alpha-La IgE
      titers ranged from 0.6 to 125 IU/ml. Highly purified tryptic peptides from native
      and disulfide-bond-reduced alpha-La were obtained by reverse phase
      chromatography. By ELISA technique using immobilized native protein or peptides,
      11 of the 19 sera reacted exclusively with intact protein while 8 of them also
      presented a specific IgE response to different tryptic peptides. Polyclonal IgE
      population specificity was not related to anti-bovine alpha-La IgE levels.
      Sequence (17G-K58) and larger peptides sharing this sequence were most strongly
      and frequently recognized. Competitive ELISA inhibition tests confirmed this IgE
      specific response and gave also clear evidence for IgE binding to smaller
      peptides corresponding to sequences (6C-R10):S-S:(115L-L123) and (109A-L123). IgE
      binding to native alpha-La and large peptides confirmed the importance of
      conformational epitope(s). However, in some sera reduced and S-alkylated peptide
      (59I-K94) exhibited a similar or higher IgE binding capacity than the native
      corresponding fragment, suggesting the existence of sequential epitope(s) exposed
      through protein denaturation. Moreover, IgE binding sequences were also located
      within hydrophobic regions of alpha-La and/or within parts with high sequence
      homology to human alpha-La.

PMID- 9250596
TI  - Images in allergy and immunology. Structure and epitopes of Bet v1.

PMID- 9250597
TI  - Adhesion molecules in atopic dermatitis: upregulation of alpha6 integrin
      expression in spontaneous lesional skin as well as in atopen, antigen and
      irritative induced patch test reactions.
AB  - Atopic dermatitis is a lymphocyte-mediated skin disease. We studied the
      expression of the adhesion molecule alpha6 integrin by immunohistochemistry in
      spontaneous atopic inflammation as well as during the eliciting phase of atopen
      (Dermatophagoides pteronyssinus), antigen (nickel sulfate) and irritative
      (anthralin) induced patch test reactions in atopic skin. Results were compared
      with nickel sulfate patch test reactions in normal skin. A role of the alpha6
      integrin, expressed at the luminal side of blood vessels, for T cell migration in
      lesional atopic skin was supposed. In normal human skin the alpha6 integrin was
      weakly expressed by blood vessels and by basal epithelial cells of the epidermis.
      In acute and chronic lesional skin of patients with atopic dermatitis dramatic
      upregulation of alpha6 integrin expression was observed on endothelial cells and
      in the epidermis. The similar pattern of upregulated suprabasal alpha6 integrin
      expression was established in the patch test reactions 48 h after atopen and
      antigen application or irritation of the skin without differences in dependence
      on the eliciting substance. No difference of alpha6 integrin expression was seen
      between atopic and normal skin. Tumor necrosis factor alpha, interleukin-1,
      interleukin-4 and interferon gamma play a role in atopic inflammation. Tumor
      growth factor beta and interleukin-6 are mitogenic/growth factors for
      keratinocytes. For this reason the effect of these cytokines and of phorbol-12
      myristate-13-acetate on the expression level of alpha6 integrin was tested in
      short-term skin organ culture of normal and atopic skin as well as in
      keratinocyte cultures. In these assays no cytokines had an effect on alpha6
      integrin expression suggesting another mechanism which regulates this integrin.
      However, the increased expression of alpha6 integrin in the suprabasal epidermis
      is associated with a T cell influx into the epidermis. We speculate that the
      alpha6 integrin expression may lead to an epidermotropism of T cells during
      inflammation.

PMID- 9250598
TI  - Eosinophil-derived proteins in postprandial (food-dependent) exercise-induced
      anaphylaxis.
AB  - BACKGROUND: Postprandial exercise-induced anaphylaxis (PPEIAn) is a form of EIAn
      in which the ingestion of food before the exercise is associated with the onset
      of symptoms. Skin reactivity and the presence of specific serum IgE to several
      food allergens suggest the occurrence of food-dependent allergic mechanisms.
      METHODS: In order to study the involvement of eosinophils in the pathogenesis of
      PPEIAn we measured the changes in serum eosinophil cationic protein (ECP) and
      eosinophil protein X/eosinophil-derived neurotoxin (EPX/EDN) levels in 6 patients
      with PPEIAn, subjected to three separate challenges with either suspected foods
      only, exercise after a meal without or with suspected food ingestion. RESULTS: We
      found serum levels of both eosinophil-derived proteins increased only in
      challenges including both exercise and suspected food ingestion. Symptoms of
      anaphylaxis occurred in 3 of these patients. CONCLUSIONS: The increased release
      of eosinophil basic proteins in PPEIAn patients, caused by physical exercise
      following ingestion of suspected foods, is not obligatory for the definition of
      the syndrome.

PMID- 9250599
TI  - Specific pattern of circulating endothelial adhesion molecules in HIV-associated
      Kaposi's sarcoma.
AB  - BACKGROUND: Circulating endothelial adhesion molecules have been found to be
      increased in states of immune activation, but little is known about their
      significance in the assessment of endothelial neoplasms. One of the most common
      tumors supposed to be derived from endothelial origin is HIV-associated Kaposi's
      sarcoma (KS). METHODS: Plasma concentrations of sCD54 (= intercellular adhesion
      molecule-1), sCD106 (= vascular cell adhesion molecule-1), and sCD62E (= E
      selectin) were quantified by sandwich ELISA in 54 AIDS patients who were either
      free of active opportunistic disorders (n = 15, AIDS controls), or suffering from
      acute infections (n = 16), or exhibiting KS (n = 23), and in 18 age- and sex
      matched healthy HIV-negative controls. RESULTS: Both sCD54 and sCD106 plasma
      levels were consistently increased in all AIDS patients irrespective of
      concurrent opportunistic disorders (p < 0.005), while sCD62E levels were not
      altered in AIDS patients without KS (p > 0.05). In KS patients, sCD62E
      concentrations were decreased both compared to healthy (p = 0.0007) and to AIDS
      controls (p = 0.04), and stimulated sCD54 levels were less elevated than those of
      AIDS controls (p = 0.02). Plasma concentrations of all three adhesion molecules
      did not correlate to KS tumor stage. CONCLUSION: There appears to be a specific
      pattern of circulating endothelial adhesion molecules in AIDS patients with
      associated KS. Although the present findings do not support a role for their
      determination as tumor markers, they might be involved in KS tumor pathogenesis.

PMID- 9250600
TI  - Lactose-intolerance may induce severe chronic eczema.
AB  - The primary acquired lactase deficiency of the adult is known to cause various
      disturbances in the gastrointestinal tract while extraintestinal symptoms are
      unusual. Here we report on a histologically proven chronic eczema requiring
      corticosteroid treatment for several months. It was obviously induced by a
      concomitant lactose intolerance since the introduction of a lactose-free diet led
      to a complete disappearance of the eczema and allowed the discontinuation of the
      corticosteroid treatment. As far as we know, this is the first case report of an
      eczema caused by a lactose intolerance.

PMID- 9250602
TI  - Modelling intracellular fatty acid transport: possible mechanistic role of
      cytoplasmic fatty acid-binding protein.
AB  - A computer model is presented in which the role of cytoplasmic fatty acid-binding
      protein (FABP) in the intracellular translocation of fatty acids (FA) from one
      membrane to an opposite membrane is studied. The model consists of a cubical
      space, in which FABP and FA are allowed to diffuse at random. The amount of FA
      released from the donor membrane and reaching an opposite acceptor membrane is
      calculated in a variety of conditions. The data provided by the various
      simulations suggest that FABP can play a significant role in intracellular FA
      transport only if FABP is able to take up FA directly from FA containing
      membranes and to directly deliver FA to an acceptor membrane, thus preventing the
      unfavourable thermodynamical situation in which FA must solubilize in an aqueous
      environment prior to binding to FABP.

PMID- 9250601
TI  - Molecular mechanism of cellular uptake and intracellular translocation of fatty
      acids.
AB  - The molecular mechanism of the transport of long-chain fatty acids across
      cellular membranes and the necessity and precise functioning of specific proteins
      in this process are still unclear. Various alternative mechanisms have been
      proposed. Studies with artificial phospholipid bilayers support the concept that
      fatty acids may enter and traverse the plasma membrane without the involvement of
      proteins. On the other hand, a number of membrane-associated fatty acid-binding
      proteins (FABPs) have been described which putatively function as acceptors for
      fatty acids released from albumin or from lipoproteins. Albumin binding proteins
      located at the outer cell surface could play an additional role in the delivery
      of fatty acids. The subsequent transmembrane translocation of fatty acids could
      take place by a membrane protein acting as a translocase, or by simple diffusion
      of fatty acids through either the phospholipid bilayer or a pore or channel
      formed by one or more membrane fatty acid transporters. At the inner side of the
      plasma membrane, the fatty acid is bound to a cytoplasmic FABP, which serves to
      buffer the intracellular aqueous fatty acid concentration. The direction of fatty
      acid migration through the plasma membrane most likely is governed by the
      transmembrane gradient of fatty acid concentration, assisted to some extent and
      in selected tissues by co-transport of sodium ions. The intracellular transport
      of fatty acids from the plasma membrane to the sites of metabolic conversion
      (oxidation, esterification) or subcellular target (signal transduction) is
      greatly facilitated by cytoplasmic FABPs. In conclusion, cellular uptake and
      intracellular translocation of long-chain fatty acids is a multi-step process
      that is facilitated by various membrane-associated and soluble proteins. The
      mechanism of cellular uptake of fatty acids probably involves both a passive and
      carrier-mediated transmembrane translocation.

PMID- 9250603
TI  - Regulation of FAT/CD36 gene expression: further evidence in support of a role of
      the protein in fatty acid binding/transport.
AB  - Much biochemical evidence has implicated rat adipocyte CD36 (FAT) in membrane
      binding and transport of long-chain fatty acids (FA). Expression of the mRNA
      favored tissues with active FA metabolism and was upregulated in vivo with
      diabetes and with high fat feeding. In culture, CD36 mRNA was a strong marker of
      preadipocyte differentiation and was modulated by the same factors effective on
      mRNAs coding for other proteins involved in FA metabolism. In preadipocytes, long
      chain FA or 2-bromopalmitate but not short-chain FA strongly induced CD36 mRNA
      within 8 h to an optimum within 24 h. Removal of the FA resulted in a decay of
      CD36 mRNA with a half life of about 12 h. In differentiated adipocytes, levels of
      CD36 mRNA were downregulated by the 3': 5'-cyclic adenosine monophosphate, cAMP,
      analog, 8-(4-chlorophenylthio) adenosine, 8-CPT, at concentrations of 1-100
      microM. The effect, observed within 6 h, was optimal after 18 h and independent
      of the action of 8-CPT to mobilize FA. Regulation of CD36 expression by factors
      effective on expression of other proteins implicated in FA metabolism is
      consistent with its role in membrane FA transport.

PMID- 9250604
TI  - Manipulation of the fate of long chain polyunsaturated fatty acids in cultured
      cells.
AB  - We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC
      PUFA) from their precursors in cultured cells undergoing physiological
      modifications, or under the influence of lipid-lowering drugs or ethanol. The
      formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid
      (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of
      differentiation, and declines when differentiation is complete, in concomitance
      with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the
      biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase
      inhibitor simvastatin (S), an effect which is reverted by mevalonate and other
      intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis
      by S occurs at concentrations lower than those required for maximal inhibition of
      cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the
      biosynthesis of LC-PUFA while potentiating the incorporation of acetate into
      cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell
      differentiation and complex interactions between LC-PUFA and cholesterol
      synthesis occur, as judged from data obtained through pharmacological
      manipulations.

PMID- 9250605
TI  - Effect of increased uptake of plasma fatty acids by the liver on lipid metabolism
      in the hepatocellular nuclei.
AB  - The nucleus contains different lipids. The aim of the present study was to
      examine whether increased uptake of free fatty acids by the liver affects lipid
      metabolism in the hepatocellular nuclei. The experiments were carried out on
      three groups of Wistar rats: I - male, control; II - male, heparin-treated, and
      III - female. [14C]-palmitic acid suspended in rat donor serum was administered
      intravenously 5 and 30 min before tissue samples were taken. Lipids were
      extracted from isolated liver nuclei and separated into different fractions
      (phospholipids - PH, monoacylglycerols - MG, diacylglycerols - DG, cholesterol -
      CH, free fatty acids - FFA, triacylglycerols - TG and cholesterol esters - CHE).
      It was found that 5 min after administration of the label all isolated nuclear
      lipid fractions were radioactive. Most of the radioactivity was located in the
      fraction of PH, TG and FFA. Elevation in the plasma FFA concentration (heparin
      treated group) resulted in increased incorporation of [14C]-palmitic acid into
      the nuclear lipids and changes in its distribution. In the female rats the
      radioactivity of nuclear lipids was higher than in the male-controls. There were
      also differences in the percentage distribution of the radioactivity in different
      lipid fractions between the two groups. The concentration of PH and TG in the
      nuclei increased only in the heparin-treated but not in the female rats. However,
      specific activity of the nuclear PH and TG increased in with both groups compared
      to the male-control group. It is concluded that (a) the blood-borne FFA rapidly
      enter the nuclear lipid pool and (b) increased uptake of the plasma-borne FFA by
      the liver affects the nuclear lipid metabolism.

PMID- 9250606
TI  - Fatty acid acylation of platelet proteins.
AB  - A variety of fatty acids can become covalently attached to platelet proteins by
      thioester linkage. These fatty acids include palmitate, myristate, stearate,
      arachidonate, and eicosapentaenoate. More than 20 platelet proteins can be
      acylated by fatty acids. Several of the acylated platelet proteins have been
      identified, including glycoprotein Ib beta, glycoprotein IX, P-selectin, G
      protein alpha subunits, and CD9. This report reviews the fatty acid acylation of
      platelet proteins.

PMID- 9250607
TI  - Long-term effects of fatty acids on cell viability and gene expression of
      neonatal cardiac myocytes.
AB  - Fatty acids are the most important source of energy for the adult heart. However,
      cardiac substrate preference changes during development and alters in
      pathophysiological states. Fatty acids have also been shown to be involved in
      signal transduction pathways, thereby affecting gene expression in various cell
      systems. In the present paper the significance of changes in substrate preference
      and the potential role of fatty acids in signal transduction in the cardiomyocyte
      are briefly reviewed. Furthermore, the development of a cellular model system,
      useful in exploring the long-term effects of fatty acids on the normal and
      hypertrophic cardiomyocyte, is described. Some aspects of this model system are
      illustrated by showing the effects of different fatty acid species on cell
      viability and the effects of fatty acids on the expression of heart type fatty
      acid-binding protein (H-FABP), a 15 kDa protein thought to be involved in
      intracellular trafficking of fatty acids. To this end primary cultures of rat
      neonatal ventricular myocytes were kept in defined medium containing various
      (combinations of) substrates for up to 48 h. First, the effects of prolonged
      exposure to different fatty acid species, complexed to BSA, on cell viability
      were investigated. Exposure of the cells to saturated fatty acids (C16:0 or
      C18:0), but not mono-unsaturated (C16:1 or C18:1) fatty acids, resulted in cell
      death, as evidenced by the release of intracellular proteins like lactate
      dehydrogenase. The detrimental effects of saturated fatty acids were nullified by
      the co-addition of mono-unsaturated fatty acids. Accordingly, the combination of
      C16:0/C18:1 was used to examine the effects of fatty acids on the expression of H
      FABP. Therefore, the cells were incubated with either (i) glucose only, (ii)
      fatty acids only, or (iii) glucose plus fatty acids. Incubation with fatty acids
      (with or without glucose) resulted in a nearly four-fold increase of the H-FABP
      mRNA level. Similarly, at the protein level the cellular H-FABP/LDH ratio
      increased almost two-fold. In hypertrophic cardiomyocytes (stimulated with the
      alpha1-adrenergic agonist phenylephrine) the stimulatory effect of fatty acids on
      H-FABP expression was mitigated. These findings strongly suggest that fatty acids
      are able to modulate gene expression in the context of the cardiac muscle cell.

PMID- 9250608
TI  - Regulation of gene transcription by fatty acids, fibrates and prostaglandins: the
      phosphoenolpyruvate carboxykinase gene as a model.

PMID- 9250609
TI  - Nonesterified fatty acids in the pathogenesis of hypertension: theory and
      evidence.
AB  - This paper approaches the hypothesis that fatty acids contribute to hypertension
      by examining possible interactions of nonesterified fatty acids with renal
      pressure-natriuresis, peripheral vascular resistance, and the central nervous
      barostat, three loci where long-term regulation of blood pressure is probably
      controlled. By inhibiting aldosterone secretion, nonesterified fatty acids may
      lower blood pressure by facilitating pressure-natriuresis. Oxygenated metabolites
      of fatty acids appear to stimulate aldosterone secretion. In different
      experimental situations, fatty acids either constrict or dilate arteries. There
      is no evidence of an effect of fatty acids on the central nervous barostat, but
      they do sensitize peripheral vessels to alpha-adrenergic stimuli. Obesity and
      diabetes are marked by increased incidence of hypertension, and elevated levels
      of fatty acids or their P450 oxygenated metabolites may contribute to this
      association. Drugs that influence plasma fatty acids, like heparin, do not have
      reproducible effects on blood pressure. Experimental evidence suggests but does
      not prove that nonesterified fatty acids can affect the long-term set-point of
      blood pressure.

PMID- 9250610
TI  - Polyunsaturated fatty acids regulate lipogenic and peroxisomal gene expression by
      independent mechanisms.
AB  - Polyunsaturated fatty acids of the (n-6) and (n-3) families uniquely coordinate
      hepatic lipid synthesis and oxidation by suppressing the transcription of hepatic
      genes encoding lipogenic and glycolytic enzymes while concomitantly inducing the
      activity of enzymes in mitochondrial and peroxisomal fatty acid oxidation.
      Recently a group of fatty acid activated nuclear transcription factors termed
      peroxisome proliferator activated receptors (PPARs) were cloned. The discovery of
      PPARs led us to hypothesize that polyunsaturated fatty acids coordinately
      modulated the transcription of lipogenic and oxidative genes via a PPAR mediated
      process. Rats and mice were fed a potent PPAR activator, 5,8,11,14
      eicosatetraynoic acid (ETYA), to ascertain if the expression of hepatic fatty
      acid synthase and peroxisomal acyl-CoA oxidase were coordinately suppressed and
      induced in response to PPAR activation. Expectedly, ETYA increased peroxisomal
      acyl-CoA oxidase mRNA abundance, but PPAR activation neither suppressed fatty
      acid synthase transcription nor reduced the level of fatty acid synthase mRNA. In
      fact, ETYA prevented the suppression of hepatic fatty acid synthase expression
      that characteristically results from feeding corn oil. Fatty acid composition
      analyses indicated that ETYA interfered with 18:2 (n-6) conversion to 20:4 (n-6).
      Thus, it appears that PPAR is not the sole factor responsible for the coordinate
      regulation of lipid synthesis and oxidation by polyunsaturated fatty acids. In
      addition, our data indicate that the active polyenoic fatty acid responsible for
      the regulation of gene transcription must undergo delta-6 desaturation.

PMID- 9250611
TI  - Trans-differentiation of myoblasts to adipoblasts: triggering effects of fatty
      acids and thiazolidinediones.
AB  - Long-chain fatty acids (LCFA) and thiazolidinediones are potent activators of
      differentiation of preadipose cells. These adipogenic effects are, at least in
      part, mediated by nuclear receptors of the peroxisome proliferator-activated
      receptor (PPAR) subfamily. This report describes the effects of these agents on
      the differentiation pathway of myoblasts. Exposure of C2C12 myoblasts to LCFA or
      thiazolidinediones prevents the formation of multinucleated myotubes and the
      expression of specific muscle markers, leading in parallel to the expression of a
      typical adipose differentiation program. Similar transdifferentiation also occurs
      in mouse muscle satellite cells maintained in primary cell culture. These
      observations indicate that PPAR activators, such as LCFA or thiazolidinediones,
      convert the differentiation pathway of myoblasts into that of adipoblasts. This
      phenomenon could explain the appearance of adipocytes into muscle which occurs in
      some pathological states characterized by an increase of fatty acid disposal,
      such as obesity or mitochondrial myopathy.

PMID- 9250612
TI  - Heart-type fatty acid binding protein - involvement in growth inhibition and
      differentiation.
AB  - Fatty acid binding proteins (FABPs) comprise a well-established family of
      cytoplasmic hydrophobic ligand binding proteins and are thought to be involved in
      lipid metabolism by binding and intracellular transport of long-chain fatty
      acids. However, from other studies role for FABPs in cell signalling, growth
      inhibition and differentiation has also been implied. In particular, the heart
      type (H-FABP) is abundantly expressed in differentiated mammary gland and its
      relationship with a very homologous (95%) mammary derived growth inhibitor (MDGI)
      was disputed. Here we give a survey on the experimental evidence for the
      existence of such protein with growth inhibitory function. After cloning of the
      bovine adipocyte-type (A-)FABP cDNA from mammary gland we conclude that the
      reported MDGI sequence actually represents a mixture of bovine H- and A-FABP and
      that the MDGI function is exerted by H-FABP. We also monitored the H-FABP level
      during differentiation of C2C12 muscle cells from myoblasts to multiply nucleated
      myotubes. H-FABP expression is clearly detected after that of the transcription
      factor myogenin which is upregulated immediately upon onset of differentiation
      and after that of the typical muscle enzyme creatine kinase. This argues against
      an active role of H-FABP in muscle development unlike the situation in the
      mammary gland.

PMID- 9250613
TI  - Accumulation of arachidonic acid in ischemic/reperfused cardiac tissue: possible
      causes and consequences.
AB  - Under physiological conditions, the content of unesterified arachidonic acid in
      cardiac tissue is very low. The bulk of arachidonic acid is present in the
      membrane phospholipid pool. Incorporation of arachidonic acid into phospholipids
      (reacylation) and liberation of this fatty acid from the phospholipid pool
      (deacylation) are controlled by a set of finely tuned enzymes, including
      lysophospholipid acyltransferase and phospholipase A2. At present, at least three
      subtypes of phospholipase A2 have been identified in cardiac structures, i.e., a
      low molecular mass group II phospholipase A2, a cytoplasmic high molecular mass
      phospholipase A2 and a plasmalogen-specific phospholipase A2. Cessation of flow
      to the heart (ischemia) gives rise to net degradation of membrane phospholipids
      accompanied by accumulation of fatty acids, including (unesterified) arachidonic
      acid. Restoration of flow to the previously ischemic cells results in a continued
      accumulation of fatty acids. The mechanism(s) underlying net phospholipid
      degradation in ischemic/reperfused myocardial tissue is (are) incompletely
      understood. Impaired reacylation, enhanced hydrolysis of phospholipids, or a
      combination of both may be responsible for the phenomena observed. Elevated
      tissue levels of arachidonic acid may exert both direct and indirect effects on
      the affected myocardium and healthy cardiac cells adjacent to the injured
      cardiomyocytes. Indirect effects might be evoked by arachidonic acid metabolites,
      i.e., eicosanoids. Arachidonic acid may directly influence ion channel activity,
      substrate metabolism and signal transduction, thereby affecting the functional
      characteristics of the ischemic/reperfused myocardium.

PMID- 9250614
TI  - Subcellular alterations in cardiac phospholipase D activity in chronic diabetes.
AB  - Several studies have suggested that myocardial phospholipase D (PLD) and its
      hydrolytic product, phosphatidic acid (PtdOH), may regulate Ca2+ movements and
      contractile performance of the heart. Since abnormal intracellular Ca2+ handling
      is a major factor of myocardial dysfunction in chronic diabetes, we examined
      subcellular changes in PLD activity in myocardium from insulin-dependent diabetic
      rats. Diabetes in rats was induced by a single i.v. injection of streptozotocin
      (65 mg/kg body wt) and 8 weeks later the ventricular tissue was processed for the
      isolation of sarcolemma, sarcoplasmic reticulum and mitochondria. Compared to age
      matched controls, the sarcolemmal, sarcoplasmic reticular and mitochondrial PLD
      activities were significantly depressed in the diabetic animals. The depressed
      sarcolemmal PLD activity was normalized, whereas the sarcoplasmic reticular and
      mitochondrial enzyme activities were partially reversed upon treating the 6-week
      diabetic rats with insulin for a period of 2 weeks. These data suggest that the
      reduction of PLD-derived PtdOH may lead to an impairment in this phospholipid
      signal transduction pathway and subsequent cardiac dysfunction in chronic
      diabetes.

PMID- 9250616
TI  - Biological complexity is under the 'strange attraction' of non-esterified fatty
      acids.
AB  - It is now clear from numerous data that non-esterified fatty acids (NEFAs) can
      act without any metabolic modification as second messengers or modulators of the
      complex signalling network which is characteristic of mammals. This network can
      respond differently to adapt the organism to the various endogenous and exogenous
      environmental situations. NEFAs have a wide range of molecular structures, and
      thus can exert different specific modulatory actions on this signalling network,
      such as amplification, inhibition or signal redirection. We have chosen the term
      'strange attractions' to describe these signalling modulations by analogy with
      the 'strange attractions' concept introduced in deterministic chaos theory. NEFAs
      can modulate the functions of mammals at all levels of organization (molecular,
      cellular, tissue, organ, etc).

PMID- 9250615
TI  - Conversion of arachidonic acid to tetradecadienoic acid by peroxisomal oxidation.
AB  - Human skin fibroblasts convert [5,6,8,9,11,12,14,15-3H]arachidonic acid to two
      radiolabeled polar metabolites that accumulate in the culture medium. Previous
      studies identified the most abundant of these products as 4,7,10-hexadecatrienoic
      acid (16:3). We have now identified the second metabolite as 5,8-tetradecadienoic
      acid (14:2). Fibroblasts deficient in mitochondrial long-chain acyl coenzyme A
      dehydrogenase produce increased amounts of 14:2 from arachidonic acid. By
      contrast, Zellweger fibroblasts which are deficient in peroxisomal beta-oxidation
      do not convert arachidonic acid to either 14:2 or 16:3. These results demonstrate
      that 14:2 can be synthesized from arachidonic acid, that this oxidative process
      occurs in the peroxisomes, and that the pathway does not function in Zellweger's
      syndrome and similar diseases where there is a genetic deficiency in peroxisomal
      beta-oxidation.

PMID- 9250617
TI  - Evoked GABA release is not mediated by N-type VDCC in the frontal cortex of awake
      rats: effects of neomycin.
AB  - The purpose of the present study was to analyze the Ca2+ channel involved in GABA
      release under resting and K(+)-evoked conditions in vivo. We used microdialysis
      to investigate the effects of the voltage-dependent calcium channel (VDCC)
      blockers neomycin, kanamycin, and omega-conotoxin GVIA, and the voltage-dependent
      Na+ channel blocker tetrodotoxin, in the frontal cortex of awake rats. The GABA
      content in frontal dialysates was analyzed by high performance liquid
      chromatography coupled to fluorescence detection. Basal GABA release was
      kanamycin, omega-conotoxin, and tetrodotoxin resistant, whereas neomycin induced
      a significant increase from the basal level. The K(+)-evoked release of GABA was
      kanamycin and omega-conotoxin resistant, but tetrodotoxin sensitive. The effects
      of neomycin were masked by the action of this drug on basal release. These
      results suggest that neomycin may affect GABA release in the frontal cortex
      through a mechanism independent of VDCC. In addition, the K(+)-evoked release of
      GABA in this cortical area was not mediated by the N-type voltage-dependent
      calcium channels, but was dependent on neural activity or TTX sensitive.

PMID- 9250618
TI  - Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination
      associated with NMDA-induced lesions of the rat lateral hypothalamus.
AB  - Excitotoxins have been widely used to make lesions in the brains of experimental
      animals because they have the ability to destroy neurones while sparing fibres of
      passage. Because loss of fibres of passage can confound the interpretation of
      lesion effects, this property is of considerable value. Recently, however, there
      have been reports indicating that excitotoxins acting at different sites within
      the rat CNS not only destroy neurones but also strip myelin from fibres and
      compromise the integrity of the blood-brain barrier. However, some reports also
      indicate that the myelin content of the lesioned area recovers. Excitotoxic
      lesions of the lateral hypothalamus have been shown to produce local
      demyelination. The present studies sought to investigate this effect further by
      (1) defining the time course of demyelination and possible remyelination after
      excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate
      (NMDA); (2) establishing the relationships between neuronal loss, de- and
      remyelination after various doses of NMDA; and (3) examining the integrity of the
      blood-brain barrier using an immunohistochemical probe. Our data show that after
      injection of NMDA into the lateral hypothalamus there was neuronal loss, blood
      brain barrier disruption (followed by recovery over approximately 12 days),
      triggering of reactive gliosis, invasion of the lesioned area by cells from
      outwith the CNS, demyelination over an area coexistent with but not exceeding the
      area of neuronal loss, and remyelination. Remyelination occurred over a period of
      3 months following the production of the lesion and was associated initially with
      blood vessels. It occurred across the whole of the lesioned area, not by
      encroachment from the borders. All doses of NMDA that produced neuronal death
      also produced demyelination. These data confirm that excitotoxic lesions of the
      lateral hypothalamus demyelinate fibres, but show for the first time that
      remyelination occurs here. They are consistent with reports concerning
      excitotoxin actions at other CNS sites and indicate that de- and remyelination
      after excitotoxic lesions is a ubiquitous process. Consideration should be given
      to this when using excitotoxins to make fibre-sparing lesions.

PMID- 9250619
TI  - Neuroprotective effect of graded postischemic reoxygenation in spinal cord
      ischemia in the rabbit.
AB  - Early ischemia/reperfusion-induced changes of four phospholipid compounds bound
      to the inner cell membrane leaflet, i.e., phosphatidic acid, inositol
      phospholipids, serine phospholipids, and ethanolamine plasmalogens, were studied
      in a model of spinal cord ischemia in the rabbit during normoxic and graded
      postischemic reoxygenation. Light and electron microscopic analysis after
      normoxic reoxygenation disclosed neuronal membrane argyrophilia of the
      interneuronal pool located in lamina VII of L4-L6 segments. The number of small
      neurons (10-25 microm in diameter) affected by somatodendritic argyrophilia was
      greatly reduced, and concomitantly the ultrastructure of the endoplasmic
      reticulum, mitochondria, and Golgi complexes remained almost undamaged when
      graded postischemic reoxygenation had been applied. A statistically significant
      increase of phosphatidylserine and ethanolamine plasmalogen levels, and a
      decrease of phosphatidic acid, were detected after a short-lasting graded
      postischemic reoxygenation. The formation of thiobarbituric acid-reactive
      substances was significantly reduced during 60 min of graded postischemic
      reoxygenation and remained close to control or ischemic levels. The present data
      indicate that graded postischemic reoxygenation, which is considered to be
      neuroprotective, can prevent neuronal argyrophilia and the development of
      reperfusion-induced alterations of organelles. Moreover, reoxygenation can
      positively modify ischemia-induced changes of some membrane-bound phospholipids.

PMID- 9250620
TI  - Endocytosis of horseradish peroxidase by brain microvascular and umbilical vein
      endothelial cells in culture: an ultrastructural and morphometric study.
AB  - The ability to form tight junctions and the paucity of fluid phase endocytosis
      showed by brain microvacular endothelial cells (BMECs) make up the structural
      basis of the blood-brain barrier (BBB). Most studies on cultured BMECs focused on
      intercellular junctions, whereas endocytosis received lesser attention. We
      studied endocytosis of horseradish peroxidase in primary and passage 1 and 2 BMEC
      cultures from rat brain as well as in human umbilical vein endothelial cell
      (HUVEC) culture. Endocytic activity was also analyzed in passage 1 BMECs treated
      with lipopolysaccharide (LPS, 1 microg/ml for 4 h), which mimics BBB disruption
      in bacterial meningoencephalitis. The percent of cytoplasmic area occupied by
      endocytic profiles (vesicles <70 nm and vacuoles >70 nm) and their mean number
      per cell were significantly lower in primary and passaged BMEC than in HUVEC
      cultures. The area and number of endocytic profiles significantly increased in
      BMECs after exposure to LPS. BMECs cultured under standard conditions may be a
      suitable model for studying the mechanism of increased fluid phase endocytosis in
      certain diseases and injury states.

PMID- 9250621
TI  - Monkey superior colliculus activity during short-term saccadic adaptation.
AB  - This article concerns the neural mechanisms that underlie short-term saccadic
      adaptation in the rhesus monkey. By means of a consistent intrasaccadic target
      displacement, the relation between visual input and motor output was gradually
      changed in three monkeys, such that they made hypometric saccades. During this
      process, the activity of saccade-related burst neurons in the intermediate and
      deep layers of the Superior Colliculus (SC) was recorded in two of the monkeys.
      Our findings show that, like in humans, only saccades evoked within a restricted
      field around the adaptation target were adapted. However, unlike in humans, the
      kinematic properties of adapted saccades also changed systematically during the
      adaptation process. Typically, adapted saccades were slower and had a longer
      duration than would be expected on the basis of the main sequence for nonadapted
      visually guided movements. During adaptation, saccade-related activity of units
      in the SC remained appropriate for the saccade that was required to foveate the
      initial target, rather than for the saccade that was actually made. This means
      that adaptation caused a dissociation between SC activity and the ensuing
      saccade. Thus, the activity of the colliculus was better described in "required
      eye displacement coordinates" than in "actual eye displacement coordinates." Our
      data provide further evidence for the hypothesis that short-term saccadic
      adaptation acts at a level downstream from the SC, presumably at a stage that
      determines the kinematics of saccadic eye movements.

PMID- 9250622
TI  - Functional transitions between epileptiform-like activity and associative memory
      in hippocampal region CA3.
AB  - Clinical and experimental observations indicate that the hippocampus is critical
      in the formation of declarative memories. Interestingly, electrophysiological
      studies have demonstrated that the region also has a particularly low seizure
      threshold, where globally synchronous synaptic activity can occur. By using a
      detailed biophysical model of area CA3, it is shown how septal cholinergic
      modulation, through three distinct mechanisms, can interact with intrinsic and
      synaptic conductances to influence population behavior. A dissection of each
      mechanism demonstrates a variety of population firing activity ranging from fully
      synchronized behavior to a mixture of repetitive bursting and oscillations in
      reduced subsets of neurons, ideal for forming accurate associations during a
      learning and recall task.

PMID- 9250623
TI  - Sex steroids modulate NADPH-diaphorase expression in the postnatal adrenal
      neurons of the rat.
AB  - The rat adrenal gland contains nitric oxide-producing ganglion cells,
      contributing to its innervation. In a previous study postnatal number and
      morphology of these adrenal neurons were analyzed by NADPH-diaphorase
      histochemistry in the two sexes. A transient sex-related difference in the number
      of NADPH-diaphorase positive neurons per adrenal gland was found at postnatal day
      10, when the number of stained neurons in males was nearly twice that found in
      females. In the present work we studied the effects of perinatal hormonal
      manipulation on the number of adrenal NADPH-diaphorase-positive neurons during
      the second postnatal week. The number of labeled adrenal neurons at postnatal day
      10 was higher in females receiving perinatal androgen treatment than in control
      untreated females, and was similar to that of control untreated males. In
      contrast, in males that underwent perinatal deprivation of testosterone the
      number of labeled adrenal neurons was lower than in control males, and similar to
      that of control females. These differences were found in both the adrenal cortex
      and medulla. In males and in testosterone-treated females there was a higher
      proportion of stained multipolar neurons than in females and in androgen-deprived
      males. No intergroup differences were found in the size of stained neurons. Thus,
      we demonstrated that the postnatal difference in the number of NADPH-diaphorase
      positive adrenal neurons in the two sexes is related to the epigenetic action of
      gonadal hormones during perinatal maturation.

PMID- 9250624
TI  - Identification of microtubule-associated protein tau isoforms in Alzheimer's
      paired helical filaments.
AB  - AD66 proteins derived from sodium dodecylsulfate (SDS) insoluble paired helical
      filaments (PHF) were isolated from Alzheimer's brain using a purification
      procedure developed previously in this laboratory, and characterized by
      immunologic and chemical cleavage methods. AD66 proteins were immunoreactive with
      antibodies that recognize the amino terminal, tubulin-binding, and carboxy
      terminal domains of microtubule-associated protein tau indicating the presence of
      the entire tau sequence in AD66 proteins. These proteins were reactive with
      antibody 423 that binds to PHF but not human adult tau. Immunologic and chemical
      cleavage studies indicated that only two of the six tau isoforms were present in
      these proteins. AD66 proteins were comprised of tau proteins containing only
      three tubulin binding domains with either a 29 amino acid insert or no amino
      terminal insert. For comparative purposes, SDS soluble PHF-tau (A68 proteins) was
      purified from Alzheimer's brains and normal adult tau purified from control
      brains. Antibody Alz-50 was immunoreactive with PHF-tau or normal tau regardless
      of alkaline phosphatase treatment while immunoreactivity was only observed with
      dephosphorylated AD66 proteins. A second phosphorylated epitope on AD66 proteins
      but not PHF-tau or normal tau proteins was demonstrated with antibody PHF9. These
      data suggest that AD66 proteins represent a more phosphorylated form of tau than
      PHF-tau or normal tau proteins. Two-dimensional gel electrophoresis demonstrated
      that AD66 proteins have higher apparent molecular weights and lower pI values
      than normal tau, differences possibly due to the greater phosphorylation observed
      in these proteins.

PMID- 9250625
TI  - Downregulation of corticotropin-releasing factor mRNA, but not vasopressin mRNA,
      in the paraventricular hypothalamic nucleus of rats following nutritional stress.
AB  - Stress can cause disturbance of homeostasis to result in illness. Stress can also
      induce various gene expression in different neuronal systems. For example,
      nutritional stress induced by acute food deprivation upregulates corticotropin
      releasing factor (CRF) mRNA, whereas osmotic stress increases vasopressin (VP)
      mRNA. However, it is unknown if nutritional stress induced by chronic food
      deprivation has synergistic effects on CRF and VP mRNAs. We have used in situ
      hybridization in conjunction with quantitative autoradiography to demonstrate
      that nutritional stress induced by a 4-day food deprivation results in a body
      weight loss with a significant decrease of CRF mRNAs, but not VP mRNAs in the
      paraventricular hypothalamic nucleus (PVN) of Sprague-Dawley rats. The present
      study has thus indicated that a chronic nutritional stress does not have
      synergistic effects on CRF and VP mRNAs. The decrease of CRF mRNAs is obviously
      related to the body-weight loss induced by food deprivation. This study thus
      supports a notion that the CRF, but not VP, neurons in the PVN play an important
      role in their neuroadaptation associated with body weight loss. Thus, it is
      conceivable that downregulated CRF neurons in the hypothalamus could be involved
      in pathogenesis of human eating disorder with severe weight loss, whereas
      upregulated CRF neurons could be associated with an opposite form of the eating
      disorder that causes obesity.

PMID- 9250626
TI  - What are the underlying sources of racial differences in health?

PMID- 9250627
TI  - Race and health: basic questions, emerging directions.
AB  - PURPOSE: This paper examines the scientific consensus on the conceptualization of
      race, identifies why health researchers should analyze racial differences in
      morbidity and mortality and provides guidelines for future health research that
      includes race. METHODS: Examines scientific dictionaries and reviews the social
      science, public health and medical literature on the role of race in health.
      RESULTS: First, this paper reviews the evidence suggesting that race is more of a
      social category than a biological one. Variation in genotypic characteristics
      exists, but race does not capture it. Second, since racial categories have
      historically represented and continue to reflect the creation of social,
      economic, and political disadvantage that is consequential for well-being, it is
      important to continue to study racial differences in health. Finally, the paper
      outlines directions for a more deliberate and thoughtful examination of the role
      of race in health. CONCLUSIONS: Race is typically used in a mechanical and
      uncritical manner as a proxy for unmeasured biological, socioeconomic, and/or
      sociocultural factors. Future research should explore how clearly delineated
      environmental demands combine with genetic susceptibilities as well as with
      specified behavioral and physiological responses to increase the risk of illness
      for groups differentially exposed to psychosocial adversity.

PMID- 9250628
TI  - Improving question wording in surveys of culturally diverse populations.
AB  - PURPOSE: The purpose of this paper is to briefly describe a theoretical model
      articulating cognitive theory and sources of potential response bias resulting
      from racial or ethnic cultural experience to survey questions that deal with
      health behavior. The theory components are then evaluated using questions
      obtained from national health surveys conducted by the National Center for Health
      Statistics and Centers for Disease Control and Prevention. The analysis explores
      the effects of four cognitive tasks involved in responding to questions as
      specified by the model: question interpretation, information retrieval from
      memory, judgment formation, and response editing. Implications for
      epidemiological research are considered. METHODS: Data were collected from a
      purposive sample of 423 adults aged 18 through 50 who were recruited to ensure
      equal numbers of African American, Puerto Rican, Mexican American, and non
      Hispanic white respondents, stratified by age, gender, and education. Individual
      questions were selected for evaluation to ensure variation by topic and question
      format. Probes related to each of the cognitive tasks were designed to obtain
      insight into the underlying cognitive processes used by respondents to answer
      survey questions. All statistical analyses used logistic regression or ordinary
      least squares multiple regression as appropriate. RESULTS: Variation by
      race/ethnicity was found in the way respondents defined physical activity in a
      series of questions used in the Centers for Disease Control and Prevention
      Behavioral Risk Factor Surveillance System (BRFSS). Gender and race/ethnicity
      appeared to influence interpretation in the absence of specific cues in the
      question format about how to respond. Strategies used to retrieve information
      from memory did not appear to be influenced by respondent culture; however,
      frequency of the event was associated with the recall strategy in that more
      frequent or regular events were more likely to result in estimates about
      frequency, whereas unusual or seldom occurring events were counted. Effects of
      race/ethnicity on judgment formation seem to be reflected in the propensity of
      respondents' willingness to use extreme response categories. Most effects due to
      race/ethnicity were found in respondent editing of answers. Race/ethnicity was
      found to be associated with a social desirability trait; with willingness to
      disclose socially undesirable behavior, particularly to interviews from racial or
      ethnic groups that differed from the respondent; and with the tendency to
      overreport socially desirable behavior. CONCLUSIONS: Overall, the results of this
      research suggest several ways in which the validity of questions about risk
      behavior can be improved. In designing such questions, the investigator should
      envision the interview as a structured conversation in which ordinary
      conversational norms apply. Thus, questions that might request redundant
      information or that are threatening to the respondent need to be asked in ways
      that minimize these effects. Using interviewers of the same racial or ethnic
      group is important. Attending to the order of questions to ensure that redundant
      information is not requested is important. Writing questions to ensure that where
      response cues occur they lead the respondent to answer in unbiased ways is also
      important. Testing questions for potential racial or ethnic bias before using
      them is also important, even if the questions have been used successfully with
      population groups other than that or those included in a study.

PMID- 9250629
TI  - Effects of marital status on the risk of mortality in poor and non-poor
      neighborhoods.
AB  - PURPOSE: The purpose of this paper is to consider whether the mortality risks
      associated with marital status are conditioned by the socioeconomic quality of
      neighborhoods. METHODS: The analysis is based on the first National Health and
      Nutrition Examination Survey 1971-1974 (NHANES I), and the 1987 NHANES I
      Epidemiologic Followup Survey (NHEFS). Cox proportional hazards regressions were
      used to assess whether the effect of marital status on the risk of all-cause and
      cause-specific mortality is altered by local area poverty. Analyses are
      stratified by age, sex, and urbanicity. RESULTS: The interaction between
      neighborhood poverty and marital status is suggested for non-elderly men,
      particularly for cancer mortality and for men in urban areas. Interaction effects
      are evident among older women residing in urban areas. CONCLUSIONS: The absence
      of a spouse elevates the risk of mortality but this risk is moderately higher in
      impoverished neighborhoods, notably in urbanized areas, for non-elderly men and
      elderly women. Future studies with larger samples of non-married persons where
      marital status changes are incorporated are needed to improve our understanding
      of the joint mortality effects of local area poverty and marital status.

PMID- 9250630
TI  - Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved
      in incorporating putative genetic susceptibility markers into epidemiological
      studies.
AB  - PURPOSE: Heterocyclic amines (HCAs), which are found mainly in well-cooked meat,
      require metabolic activation to function as mutagens and animal carcinogens.
      Enzymes such as cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2)
      perform this task and are subject to interindividual variation. The source of
      this variation may be genetic, as in the case of NAT2, or both genetic and
      environmental as with CYP1A2. The present study examined the effect of HCAs on
      the NAT2 and CYP1A2 phenotypes in 33 males and 33 females. METHODS: The subjects
      consumed a low HCA-containing diet for 1 week followed by a high HCA diet for the
      subsequent week. The subjects were phenotyped for CYP1A2 and NAT2 at the time of
      entry into the study (free-living), 1 week later (end of low-HCA or low-induction
      diet) and 2 weeks later (end of high-HCA or high-induction diet). RESULTS:
      Consistent with genetic sources of variability, NAT2 showed little effect of a
      high-HCA diet and exhibited high intraindividual correlation. CYP1A2, in
      contrast, was induced by a high-HCA diet and exhibited a more modest
      intraindividual correlation. CONCLUSIONS: Incorporating putative genetic
      susceptibility makers in population studies requires consideration of issues of
      induction and inhibition of metabolizing enzymes, and effects of covariates.

PMID- 9250631
TI  - Genetic predictors of common disease: apolipoprotein E genotype as a paradigm.
AB  - PURPOSE: Genetic variation of a common genetic polymorphism at the structural
      locus for apolipoprotein E (apoE) has been associated with risk of elevated serum
      lipids, coronary artery disease, and Alzheimer disease, all of which are
      multifactoral disorders and are inherited in a complex fashion. Although the apoE
      polymorphism is only one risk factor in a complex pattern of inheritance, it
      gives us a foothold into the understanding of the genetic architecture of these
      disorders. However, apoE also exemplifies the complications that can arise in the
      use of genetic markers to predict disease. This paper considers the study of
      apolipoprotein E genotype effects as an example of the following analytical
      complications: changes in allele frequencies and allele effects with age,
      pleiotrophic effects of genetic loci, the existence of more than one alternative
      allele at a locus, and the expectation of a variety of interactions. METHODS:
      Publications that exemplify these complications are cited and discussed. No
      original analyses are presented. RESULTS: There is evidence that the relative
      frequency of the apoE epsilon4 allele declines with age after the sixth decade of
      life and that the effects of the APOE allele on lipids also may be age-dependent.
      Grouping of genotypes may not accurately characterize the effects of individual
      genotypes. Interactions between APOE genotype and a number of factors, including
      family history of dementia, are demonstrated for the effects of APOE in Alzheimer
      disease as well as for the effects of apoE on serum lipids. CONCLUSION: Careful
      attention must be paid to these and other analytical issues when genotype is a
      predictor.

PMID- 9250632
TI  - Ethical issues of genetic testing and their implications in epidemiologic
      studies.
AB  - PURPOSE: To discuss and summarize the ethical controversies related to genetic
      testing and screening, and their effects on the research and other professional
      activities of epidemiologists. METHODS: We reviewed the literature and proposed
      legislation to discuss the controversies related to the ethical issues of genetic
      testing in epidemiologic research. RESULTS: From a review of the literature and
      proposed legislation, we found these controversies may continue for some time and
      will probably add to the duties and difficulties of epidemiologists. It is
      important for the profession to respond to developments such as the proposed
      federal Genetic Confidentiality and Nondiscrimination Act of 1996 (Senate Bill
      1898), which is summarized here; changes in research protocols and informed
      consent forms as well as inclusion of other professionals from many disciplines
      will be necessary. In addition to revising training, and expanding their ethical
      code, epidemiologists should respond to public concerns about genetic information
      by disseminating knowledge about freedom to conduct clinical research, protection
      of the individual, and the limits of genetic information. CONCLUSIONS: The
      possibility of genetic discrimination may complicate epidemiological research
      unless the public, employers, insurers, physicians, and researchers reach a
      consensus on the meaning of, and need for, genetic information. Although ethical
      concerns are appropriate, they will make accrual of study subjects and tissue
      samples more difficult.

PMID- 9250633
TI  - Biphasic transthoracic defibrillation causes fewer ECG ST-segment changes after
      shock.
AB  - STUDY OBJECTIVE: Electrocardiographic abnormalities are common after
      transthoracic defibrillation. ECG ST-segment changes are especially problematic
      after defibrillation and may indicate ischemic or shock-induced cardiac
      dysfunction after resuscitation. Biphasic defibrillation waveforms, compared with
      monophasic waveforms, diminish shock-induced cardiac dysfunction in laboratory
      preparations. This effect has not been validated in human subjects. We therefore
      evaluated in a prospective, blinded fashion the effect of biphasic and monophasic
      transthoracic defibrillation on the ECG ST segment in 30 consecutive patients
      during surgery for the implantation of a cardioverter-defibrillator. METHODS: In
      each patient two low-energy truncated biphasic transthoracic defibrillation
      shocks (115 and 130 J) were compared with a standard clinical 200 J monophasic
      damped-sine wave shock. The biphasic shocks and the damped-sine wave shock have
      been demonstrated to have equal defibrillation efficacy of 97%. Fifteen-second
      ECG signals recorded across transthoracic defibrillation electrodes were
      digitized before ventricular fibrillation induction and immediately after each
      defibrillation attempt. The ST segments 80 msec after the J point were analyzed
      in a blinded fashion by two reviewers. The ST-segment deflection, QRS-interval
      duration, QT interval, and heart rate after each therapy were compared with
      baseline values. RESULTS: ECG ST-segment elevation was significantly greater with
      the 200-J damped-sine waveform than with either biphasic waveform. The ECG ST
      segment levels were -.55 +/- .36 at baseline, -.76 +/- .36 mm after internal
      shock, -.02-.36 mm after 115-J biphasic shock, .21 +/- .38 mm after 130-J
      biphasic shock, and 2.09 +/- .37 mm after 200-J damped-sine wave shock (P<.0001).
      QRS-interval duration, QT interval, and heart rate did not change significantly
      with any waveform. CONCLUSION: Transthoracic defibrillation with biphasic
      waveforms results in less postshock ECG evidence of myocardial dysfunction
      (injury or ischemia) than standard monophasic damped sine waveforms without
      compromise of defibrillation efficacy.

PMID- 9250634
TI  - Transvaginal ultrasound in patients with low beta-human chorionic gonadotropin
      values: how often is the study diagnostic?
AB  - STUDY OBJECTIVE: To determine how often pelvic ultrasonography diagnoses or
      excludes ectopic pregnancy (EP) in patients who present with abdominal pain or
      vaginal bleeding and a beta-human chorionic gonadotropin (beta-hCG) level lower
      than 1,000 mIU/mL. METHODS: This was a retrospective chart review of all patients
      who presented to the ED of an urban teaching hospital from August 1991 through
      July 1995 with lower abdominal pain or bleeding, a positive beta-hCG assay, and a
      quantitative beta-hCG value lower than 1,000 mIU/mL in whom pelvic transvaginal
      ultrasound was performed within 24 hours of the ED visit. Ultrasound procedures
      were performed in the radiology department by ultrasound technicians under the
      direct supervision of an attending radiologist or resident in radiology. Patients
      were excluded if they had recently delivered or undergone dilatation and
      curettage, had had a previous ultrasound examination during this pregnancy, had
      decreasing beta-hCG values, or were lost to follow-up before a definitive
      diagnosis was made. RESULTS: : A total of 111 patients met the inclusion
      criteria; 19 patients (17%; 95% confidence interval [CI], 10% to 24%) had
      diagnostic ultrasound findings. Of these, 10 findings were diagnostic of
      intrauterine pregnancy and 9 for EP. The beta-hCG values for the patients with
      diagnostic examinations ranged from 47 to 995 mIU/mL. Twenty-three study patients
      ultimately received a diagnosis of EP; of these, 9 (39%; CI, 19% to 59%) had a
      diagnostic initial ultrasound study. Five of the nine had beta-hCG values lower
      than 500 mIU/mL. CONCLUSION: Approximately one third of women with EP who present
      with beta-hCG values lower than 1,000 mIU/mL were identified with an urgent
      transvaginal ultrasound examination performed by trained ultrasound technicians.
      Clinicians should consider the use of pelvic ultrasound in patients with
      suspected EP, regardless of their beta-hCG values, particularly at institutions
      where ultrasound is readily available.

PMID- 9250635
TI  - Depression in geriatric ED patients: prevalence and recognition.
AB  - STUDY OBJECTIVE: To determine the prevalence of depression in geriatric ED
      patients and to assess recognition of geriatric depression by emergency
      physicians. METHODS: We conducted an observational survey of geriatric patients
      who presented to an urban, university-affiliated public hospital ED. A
      convenience sample of 259 patients aged 65 years or older were administered a
      brief, self-rated depression scale. Main outcome measures were prevalence of
      depression (using a predetermined cutoff score for detecting depression) and
      recognition of depression by the treating emergency physician, assessed by chart
      review. RESULTS: Seventy subjects (27%; 95% confidence interval [CI], 22% to 32%)
      were rated as depressed. Depressed and nondepressed patients were not
      significantly different with regard to age, sex, race, or education. Forty-seven
      percent of nursing home residents were depressed, compared with 24% of those
      living independently (95% CI for difference of 23%, 6% to 41%). Patients who
      described their health as poor were also more likely to be depressed (33 of 65,
      51%) than patients who reported their health to be good or fair (37 of 194, 19%)
      (95% CI for difference of 32%, 18% to 45%). Emergency physicians failed to
      recognize depression in all the patients found to be depressed on this scale (95%
      CI, 0 to 5%). CONCLUSION: The prevalence of unrecognized depression in the
      geriatric ED patients we studied was high, especially in those who reported their
      health as poor. Use of a brief depression scale can aid recognition of depression
      in older patients, leading to appropriate referral and treatment.

PMID- 9250636
TI  - Clinical trial of induced hypothermia in comatose survivors of out-of-hospital
      cardiac arrest.
AB  - STUDY OBJECTIVE: To examine the effects of moderate hypothermia (33 degrees C),
      induced by surface cooling in the ED and maintained for 12 hours in the ICU, on
      patients with anoxic brain injury after out-of-hospital cardiac arrest. METHODS:
      We conducted the study in a teaching hospital in Melbourne, Victoria, Australia.
      Participants were 22 adults who remained unconscious after return of spontaneous
      circulation following out-of-hospital cardiac arrest. This treatment group was
      studied prospectively, and a control group of 22 similar patients was studied by
      retrospective chart review. Moderate hypothermia (33 degrees C) was induced in
      the ED by means of surface cooling and maintained for 12 hours in the ICU with
      rewarming to normothermia over 6 hours; control patients were maintained at
      normothermia. RESULTS: There were no significant adverse effects of induced
      hypothermia. Cardiovascular changes included decreased pulse rate, but there were
      no significant differences in mean arterial blood pressure between the two
      groups. Small increases in serum potassium and decreases in pH at 18 hours in the
      hypothermic patients compared with normothermic controls were of no clinical
      significance. There were no septic complications. There was a significant
      increase in the number of patients with good outcome (Glasgow Outcome Coma Scale
      category 1 or 2) with induced hypothermia (11 of 22, versus 3 of 22 for
      normothermic controls; P<.05), and the mortality rate was significantly lower (10
      of 22 versus 17 of 22; P<.05). CONCLUSION: Compared with historical normothermic
      controls, outcome was significantly improved and there was no increase in
      complications when moderate hypothermia was induced in comatose survivors of out
      of-hospital cardiac arrest and maintained for 12 hours. Larger, prospective,
      randomized, controlled studies of induced moderate hypothermia in comatose
      survivors of out-of-hospital cardiac arrest are warranted.

PMID- 9250637
TI  - Aminophylline as an adjunct to standard advanced cardiac life support in
      prolonged cardiac arrest.
AB  - STUDY HYPOTHESIS: We hypothesized that the addition of aminophylline to Advanced
      Cardiac Life Support (ACLS) interventions would improve the initial resuscitation
      success rate in an animal model of prolonged cardiac arrest. METHODS: We used a
      double-blind, placebo-controlled, randomized-block design with a follow-up open
      label uncontrolled phase. We studied 24 female domestic mixed-breed swine (body
      mass, 20 to 25 kg). After electrical induction of ventricular fibrillation,
      animals were subjected to 8 minutes of no-flow cardiac arrest followed by 1
      minute of mechanical ventilation and closed-chest compressions. Nine minutes
      after arrest, equal numbers of swine received 6 mg/kg intravenous aminophylline
      (treatment group) and a saline solution placebo (control group), another minute
      of basic CPR, and standardized ACLS interventions beginning at 10 minutes.
      Initial resuscitation efforts were continued for at least 20 minutes. In all
      animals, if initial efforts failed, 6.0 mg/kg intravenous aminophylline, open
      label, and 10 minutes of additional resuscitation were administered. The primary
      outcome variables were return of spontaneous circulation (ROSC) and 1-hour
      survival. We compared groups with the two-tailed Fisher exact test. RESULTS: ROSC
      occurred in 4 of 12 animals in the treatment group (33%) and 3 of 12 in the
      control group (25%) (P=.50). Late administration of aminophylline did not result
      in ROSC in any animal. Survival to 1 hour was greater in the treatment group (4
      of 12, 33%) than in the control group (1 of 12, 8%) (P=.16). CONCLUSION: Addition
      of aminophylline to standard ACLS interventions did not increase the incidence of
      ROSC or the 1-hour survival rate in a swine model of prolonged cardiac arrest.

PMID- 9250638
TI  - Heliox therapy for pneumothorax: new indication for an old remedy.
AB  - STUDY OBJECTIVE: To evaluate a new method of treating pneumothorax: having the
      subject breathe a helium/oxygen mixture (heliox). METHODS: We conducted a
      prospective, randomized, controlled study of nine white rabbits weighing 2.5 to
      3.5 kg. Experimental pneumothorax was induced in all rabbits with the injection
      of 20 mL of air into the pleural space. The rabbits then breathed heliox, oxygen,
      or room air for 2 hours. Chest radiography was performed 5 minutes after
      induction of pneumothorax, then at 1 and 2 hours. We determined pneumothorax size
      on the chest radiograph by measuring the interpleural distance and expressing it
      as a percentage of the hemithorax. RESULTS: At 2 hours the pneumothoraces in the
      heliox group had diminished from 17.50% +/- .50% to .17% +/- .29%; in the oxygen
      breathing group they had diminished from 17.83% +/- 2.25% to .50% +/- .50%; and
      in the air-breathing group they had diminished from 18.50% +/- 3.12% to 17.33% +/
      .25%. The difference between the air-breathing and the oxygen-breathing or
      heliox-breathing animals was highly significant; no significant difference was
      found between the oxygen and heliox groups (P<.0001). CONCLUSION: Heliox, a safe
      and convenient therapy, is as effective as oxygen in reducing the volume of an
      experimental pneumothorax in rabbits.

PMID- 9250640
TI  - Analysis of parental estimates of children's weights in the ED.
AB  - STUDY OBJECTIVE: To assess the ability of parents to estimate their children's
      weight. METHODS: We assembled a convenience sample of children, newborn to 5
      years, who presented to the ED of a tertiary care hospital. Each child's mother
      or father was asked to estimate the child's weight as accurately as possible. The
      triage nurse then weighed the child on an electronic scale. An age-based formula
      was also used to estimate the child's weight. The parental estimate and the
      formula-based weight were compared with the weight indicated on the scale.
      RESULTS: One hundred seventeen children were enrolled. The mean age was 26.7
      months (range, newborn to 60 months). We analyzed agreement by plotting the
      percent difference between the weight estimates against the actual weights. The
      mean +/- SD difference between the parental estimate and the actual weight was
      6.8% +/- 9.8%. Parental estimates were accurate to within 10% of the measured
      weight in 80% of the cases (94 of 117). The mean +/-SD difference between the
      formula-derived weight and the actual weight was 13.6% +/- 17.5%. The formula was
      accurate to within 10% of the measured weight in 46% of cases (54 of 117).
      CONCLUSION: In 80% of cases, the parental estimate of the child's weight was
      within 10% of the measured weight. The parental estimate was more accurate than
      the formula-derived weight.

PMID- 9250639
TI  - EMLA versus TAC for topical anesthesia of extremity wounds in children.
AB  - STUDY OBJECTIVE: To compare the anesthetic efficacy of EMLA (eutectic mixture of
      local anesthetics) cream with that of TAC (tetracaine, adrenaline, and cocaine)
      solution for suturing uncomplicated extremity wounds. METHODS: We conducted a
      prospective, single-blind, randomized trial in a convenience sample of 32
      children, ages 5 to 18 years, who required repair of an extremity laceration.
      Eligible wounds were less than 5 cm long and less than 12 hours old. Lacerations
      involving digits, deep tissues, or musculature were excluded. Patients receiving
      medications that predisposed them to methemoglobinemia were also excluded.
      Lacerations were treated with TAC .1 mL/kg (maximum, 3.0 mL) or EMLA .15 g/kg
      (maximum, 5.0 g). Anesthesia was assessed every 10 minutes. TAC and EMLA were
      allowed to remain on the wounds for a maximum of 30 and 60 minutes, respectively.
      Anesthesia was deemed successful if no supplemental lidocaine was required, as
      judged by a suturing caregiver who was blinded to the anesthetic used. RESULTS:
      The two groups were similar with regard to age, sex, wound length and depth, and
      wound age. EMLA-treated wounds were repaired without supplemental anesthesia more
      often than TAC-treated wounds: 13 of 16 (85%) versus 7 of 16 (45%, P= .03). More
      time was required for EMLA to cause anesthesia (55 versus 29 minutes, P<.01).
      Dehiscence occurred in one wound in each group; no wound infections were
      observed. CONCLUSION: EMLA appears to be superior to TAC for anesthesia of simple
      extremity lacerations in that those wounds treated with EMLA required
      supplemental anesthesia less often. EMLA required approximately 1 hour to cause
      optimal anesthesia in open wounds. Protocols should be developed to allow
      efficient use of EMLA for anesthesia of extremity lacerations in the ED.

PMID- 9250641
TI  - Estimation of contact tympanic membrane temperature with a noncontact infrared
      thermometer.
AB  - STUDY OBJECTIVE: To investigate the agreement between contact tympanic membrane
      (TM) and noncontact infrared ear thermometers in children. METHODS: Twenty-three
      children (ages .5 to 10 years) undergoing elective tympanostomy tube placement
      were studied. An assistant used standard technique to record temperature with an
      infrared ear thermometer before and after TM temperature was obtained with a bead
      thermistor placed against the anterior-inferior quadrant of the TM. RESULTS: Mean
      temperatures were not significantly different: initial IR ear, 36.66 degrees +/
      .33 degrees C; TM, 36.71 degrees +/- .42 degrees C; final infrared ear, 36.57
      degrees +/- .33 degrees C. The mean bias (difference between initial individual
      IR ear and TM temperatures) of -.05 degrees +/-.29 degrees C and the 95% limits
      of agreement of +.53 degrees to -.63 degrees C indicate an acceptable confidence
      (error range within 3.2% of average TM temperature) for use of the initial
      infrared ear temperature as an estimate of TM temperature. CONCLUSION: The IR ear
      thermometer provides an accurate estimate of TM temperature in healthy children
      and may accurately reflect core body temperature.

PMID- 9250642
TI  - Injury recidivism in a rural ED.
AB  - STUDY OBJECTIVE: To determine the degree of injury recidivism in our ED
      population and to identify indicators of injury recidivism. METHODS: We conducted
      a retrospective review in a university-affiliated department of emergency
      medicine. The study participants were patients who presented for treatment of an
      injury. An injury recidivist was defined as a patient who presented for treatment
      of two or more unique injuries during the 1-year study period. The injured
      population was divided into three categories: (1) those with a single injury
      visit, (2) those with two to three injury visits, and (3) those with four or more
      injury visits. Demographics, mechanism of injury, and outcome data were collected
      and comparative analyses performed. RESULTS: Of the 37,360 ED patient visits,
      12,075 were injury related. Of the injury visit load, 2,838 of the 12,075 (24%)
      were injury recidivists. Of injured patients, 1,239 of 10,476 (12%) were
      recidivists. The sex distribution was similar among the groups, but the mean age
      decreased as the degree of recidivism increased. The degree of recidivism was
      higher for patients with Medicaid and for those who were uninsured. Lower mean
      medical charges per visit were found with increasing degree of recidivism, but
      the average total charges per patient increased with increasing degree of
      recidivism. Increasing degree of recidivism was associated with decreasing
      incidence of transportation-related injury but increased incidence of
      overexertion or intentional injuries. CONCLUSION: A small group of patients
      account for a significant proportion of ED injury visits. In comparison with
      injury patients seen once during the year, recidivists represent a younger
      population of lower socioeconomic status, and they are at increased risk of
      intentional injury.

PMID- 9250643
TI  - Project ASSERT: an ED-based intervention to increase access to primary care,
      preventive services, and the substance abuse treatment system.
AB  - STUDY OBJECTIVE: To test the feasibility and effectiveness of Project ASSERT, an
      innovative program developed by us to facilitate access to the substance abuse
      treatment system and to primary care and preventive services for emergency
      department patients with drug- and alcohol-related health problems. METHOD:
      Multicultural health promotion advocates (HPAs) were trained by ED personnel to
      screen patients using a health needs history, to administer a brief negotiated
      interview based on readiness-to-change principles, and to use an active referral
      process to capture the marginal capacity of the substance abuse treatment system.
      Outcome measures included (1) number of referrals to the substance abuse
      treatment system, (2) patient self-report of satisfaction with services received
      from Project ASSERT and utilization of treatment resources, and (3) changes in
      self-reported frequency of drug and alcohol use and in Drug Abuse Screening Test
      scores between enrollment and follow-up at 60 to 90 days. RESULTS: Between March
      1, 1995, and February 29, 1996, 7,118 adult ED patients were screened. Substance
      abuse was detected among 2,931 patients (41%), and 1,096 (37% of detected
      patients) were enrolled. A total of 8,848 referrals were made: 3,189 to primary
      care, 2,018 to a variety of substance abuse treatment services, 2,253 for smoking
      cessation, 339 for mammography, and 689 to other support services (eg,
      psychiatric nurse, social worker, battered women's advocate or shelter).
      Comparison of enrollment and follow-up scores for the 245 enrollees who kept a
      follow-up appointment demonstrated significant reductions, including a 45%
      reduction in severity of drug problem, a 56% reduction in alcohol use, and a 64%
      reduction in the frequency of drinking six or more drinks at one sitting. At
      follow-up, patients expressed satisfaction with Project ASSERT: 91% were
      satisfied with their referrals; 93% thought the HPAs explained things well; and
      99% thought the HPAs respected them as individuals. Among the follow-up group,
      50% self-reported that they had kept an appointment for treatment. CONCLUSION:
      Project ASSERT is an innovative approach to link ED patients with the substance
      abuse treatment system and with primary care and other preventive services. Its
      success is further demonstrated by its adoption by Boston Medical Center as a
      funded ED value-added service.

PMID- 9250645
TI  - Decreasing the burden of trauma for victims of violence.
AB  - Treating victims of violence is a routine part of emergency medicine. The
      predictable physiologic and cognitive sequelae of violent trauma are discussed,
      with a general timeline of their emergence. Strategies for the psychologic
      support in the ED of victims of violence are described.

PMID- 9250644
TI  - Domestic violence in an inner-city ED.
AB  - STUDY OBJECTIVE: To determine the prevalence of domestic violence (DV) for male
      and female ED patients and to determine the demographics of DV. METHODS: The
      study design was a descriptive written survey of adults. We used the Index of
      Spouse Abuse (ISA), a previously validated survey tool. The study was set in an
      inner-city ED with approximately 75,000 patients annually, most of them indigent.
      Patients 18 years or older who were able to give consent were included. Patients
      were excluded if they had a language barrier, were a prisoner, or had never had a
      partner. All patients presenting during 31 randomly selected 4-hour shifts during
      July 1995 were considered for the study. DV was defined as either physical or
      nonphysical on the basis of ISA scoring. The prevalence was determined for
      present (in the preceding year) and past (more than 1 year ago) abuse. Four
      violence parameters were calculated for patients who had a partner at the time of
      presentation: present physical, present nonphysical, past physical, and past
      nonphysical. Only the "past" parameters were calculated for patients who had had
      a partner in the past but had no partner at the time of presentation. We used the
      chi2 test to determine individually significant predictors of the four
      parameters. Logistic-regression models were constructed to determine the
      significant predictors of DV. Associations among the present physical, present
      nonphysical, past physical, and past nonphysical abuse categories were determined
      with McNemar's test. RESULTS: We enrolled 516 patients, 233 men and 283 women. On
      the basis of ISA scoring, 14% of men and 22% of women had experienced past
      nonphysical violence (P=.02, men versus women), and 28% of men and 33% of women
      had experienced past physical violence (P=.35). Of the 157 men and 207 women with
      partners at the time of presentation, 11% of men and 15% of women reported
      present nonphysical violence (P=.20), and 20% men and 19% of women reported
      present physical violence (P=.71). Using logistic-regression models, we
      determined that women experienced significantly more past and present nonphysical
      violence but not physical violence than men. For all four parameters, the
      victim's suicidal ideation and alcohol use were independently associated with DV.
      The victim's family history was strongly associated with past abuse. Using
      McNemar's test, we found that physical and nonphysical abuse were correlated in
      the past and present. CONCLUSION: Using a validated scale, we found that the
      prevalences of physical DV for men and women are high and that they are not
      statistically different in this population. Using chi 2 testing, we found that
      women had experienced significantly more past nonphysical violence than men;
      using logistic regression we found that they experienced significantly more
      nonphysical violence (both past and present) than men. DV was frequently
      associated with suicidal ideation, alcohol use, and family history of violence.

PMID- 9250646
TI  - Victims of violence: the role and training of EMS personnel.

PMID- 9250647
TI  - Transvaginal ultrasonography in patients with human chorionic gonadotropin values
      less [corrected] than 1,000 mIU/mL: how often is the study diagnostic?

PMID- 9250649
TI  - Role of the American Board of Emergency Medicine in the specialty of emergency
      medicine.

PMID- 9250648
TI  - Role of nuclear cardiology in the evaluation of acute coronary syndromes.
AB  - Over the last 20 years, nuclear cardiology has become a mainstay in the
      evaluation of ischemic heart disease. In the setting of acute coronary syndromes
      (myocardial infarction or unstable angina), myocardial perfusion imaging has
      emerged as an important tool in assessing the functional significance of
      angiographic coronary stenoses, evaluating the efficacy of therapeutic
      interventions, and risk-stratifying patients in the postinfarction period. Recent
      literature has demonstrated the diagnostic and prognostic value, as well as the
      cost-effectiveness, of perfusion imaging in acute chest pain syndromes and the
      diagnostic superiority of perfusion imaging compared with two-dimensional
      echocardiography. Acute perfusion imaging is now being included in the algorithm
      for the triage and management of acute chest pain syndromes. Emergency physicians
      are increasingly using nuclear cardiac imaging modalities for aid in the
      evaluation of patients who present with chest pain of uncertain origin.

PMID- 9250650
TI  - National Highway Traffic Safety Administration: vehicle weight and safety.

PMID- 9250651
TI  - Bigger is better, but not for everyone. NHTSA. National Highway Traffic Safety
      Administration.

PMID- 9250652
TI  - Asymmetric angioneurotic edema associated with thrombolysis for acute stroke.
AB  - We present a case of acute asymmetric angioneurotic edema associated with the use
      of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke.
      rtPA was administered for an acute ischemic stroke in accordance with the
      recently reported National Institute of Neurological Disorders and Stroke
      protocol, after which marked asymmetric angioedema requiring upper-airway control
      developed. Although atypical and anaphylactoid reactions have been reported with
      the use of rtPA for acute myocardial infarction, to our knowledge this is the
      first case report of asymmetric angioedema associated with the use of rtPA for
      acute ischemic stroke.

PMID- 9250653
TI  - Spontaneous rupture of the common carotid artery with pseudoaneurysm formation.
AB  - A 27-year-old man presented to the ED with an expanding neck mass after a
      Valsalva maneuver during sexual intercourse. This patient was found to have
      sustained a spontaneous rupture of the common carotid artery with pseudoaneurysm
      formation. The defect was repaired surgically with a saphenous vein patch, and
      the patient recovered. We discuss the rare occurrence of spontaneous carotid
      artery rupture and subsequent pseudoaneurysm.

PMID- 9250654
TI  - Dystonic reaction to a phenothiazine presenting as Bell's palsy.
AB  - An 11-year-old boy presented to the pediatric ED with signs and symptoms of
      Bell's palsy, which was believed to be a result of otitis media. He subsequently
      began to list to the left and could not walk erect. Because of a history of
      prochlorperazine use for vomiting, a diagnosis of a dystonic reaction to a
      phenothiazine was made, and the patient was treated with intravenous
      diphenhydramine. All symptoms resolved, including seventh nerve palsy, within 5
      minutes of treatment. Medications are often prescribed by physicians for vomiting
      without caretakers being aware of the side-effects. Dystonic reactions can be
      severe and present with myriad neurologic signs and symptoms.

PMID- 9250655
TI  - Night sweats.

PMID- 9250656
TI  - Carboxyhemoglobin after blood storage.

PMID- 9250657
TI  - Methylene blue in anaphylactic shock.

PMID- 9250658
TI  - Angioedema with oral N-acetylcysteine.

PMID- 9250659
TI  - Cockayne syndrome: defective repair of transcription?
AB  - In the past years, it has become increasingly evident that basal metabolic
      processes within the cell are intimately linked and influenced by one another.
      One such link that recently has attracted much attention is the close interplay
      between nucleotide excision DNA repair and transcription. This is illustrated
      both by the preferential repair of the transcribed strand of active genes (a
      phenomenon known as transcription-coupled repair, TCR) as well as by the distinct
      dual involvement of proteins in both processes. The mechanism of TCR in
      eukaryotes is still largely unknown. It was first discovered in mammals by the
      pioneering studies of Hanawalt and colleagues, and subsequently identified in
      yeast and Escherichia coli. In the latter case, one protein, the transcription
      repair-coupling factor, was found to accomplish this function in vitro, and a
      plausible model for its activity was proposed. While the E. coli model still
      functions as a paradigm for TCR in eukaryotes, recent observations prompt us to
      believe that the situation in eukaryotes is much more complex, involving dual
      functionality of multiple proteins.

PMID- 9250660
TI  - Metabolic inactivation of retinoic acid by a novel P450 differentially expressed
      in developing mouse embryos.
AB  - Retinoic acid (RA) is a physiological agent that has a wide range of biological
      activity and appears to regulate developmental programs of vertebrates. However,
      little is known about the molecular basis of its metabolism. Here we have
      identified a novel cytochrome P450 (P450RA) that specifically metabolizes RA. In
      vitro, P450RA converts all-trans RA into 5,8-epoxy all-trans RA. P450RA
      metabolizes other biologically active RAs such as 9-cis RA and 13-cis RA, but
      fails to metabolize their precursors, retinol and retinal. Overexpression of
      P450RA in cell culture renders the cells hyposensitive to all-trans RA. These
      functional tests in vitro and in vivo indicate that P450RA inactivates RA. The
      P450RA gene is not expressed uniformly but in a stage- and region-specific
      fashion during mouse development. The major expression domains in developing
      embryos include the posterior neural plate and neural crest cells for cranial
      ganglia. The expression of P450RA, however, is not necessarily inducible by
      excess RA. These results suggest that P450RA regulates the intracellular level of
      RA and may be involved in setting up the uneven distribution of active RA in
      mammalian embryos.

PMID- 9250661
TI  - Structural basis for the activation of phenylalanine in the non-ribosomal
      biosynthesis of gramicidin S.
AB  - The non-ribosomal synthesis of the cyclic peptide antibiotic gramicidin S is
      accomplished by two large multifunctional enzymes, the peptide synthetases 1 and
      2. The enzyme complex contains five conserved subunits of approximately 60 kDa
      which carry out ATP-dependent activation of specific amino acids and share
      extensive regions of sequence similarity with adenylating enzymes such as firefly
      luciferases and acyl-CoA ligases. We have determined the crystal structure of the
      N-terminal adenylation subunit in a complex with AMP and L-phenylalanine to 1.9 A
      resolution. The 556 amino acid residue fragment is folded into two domains with
      the active site situated at their interface. Each domain of the enzyme has a
      similar topology to the corresponding domain of unliganded firefly luciferase,
      but a remarkable relative domain rotation of 94 degrees occurs. This conformation
      places the absolutely conserved Lys517 in a position to form electrostatic
      interactions with both ligands. The AMP is bound with the phosphate moiety
      interacting with Lys517 and the hydroxyl groups of the ribose forming hydrogen
      bonds with Asp413. The phenylalanine substrate binds in a hydrophobic pocket with
      the carboxylate group interacting with Lys517 and the alpha-amino group with
      Asp235. The structure reveals the role of the invariant residues within the
      superfamily of adenylate-forming enzymes and indicates a conserved mechanism of
      nucleotide binding and substrate activation.

PMID- 9250662
TI  - Specificity of PS integrin function during embryogenesis resides in the alpha
      subunit extracellular domain.
AB  - We tested the ability of different integrin alpha subunits to substitute for each
      other during embryonic development. Two alpha subunits, which form heterodimers
      with the same betaPS subunit, are expressed in complementary tissues in the
      Drosophila embryo, with alphaPS1 expressed in the epidermis and endoderm, and
      alphaPS2 expressed in the mesoderm. As a result the two integrin heterodimers are
      present on opposite surfaces at sites of interaction between the mesoderm and the
      other cell layers where they are required for normal development. Using the GAL4
      system, we are able to rescue fully the embryonic lethality of an alphaPS2 null
      mutation with a UAS-alphaPS2 transgene, but only partially with a UAS-alphaPS1
      gene, due to partial rescue of both muscle and midgut phenotypes. Similarly we
      are able to rescue the embryonic/first instar larval lethality of an alphaPS1
      null mutation gene with UAS-alphaPS1, but only partially with UAS-alphaPS2. Each
      UAS-alpha gene, when it contains the cytoplasmic domain from the other alpha
      subunit, maintains an equivalent ability to rescue its own mutation and cannot
      fully rescue a mutation in the other alpha. We conclude that the two alpha
      subunits are not equivalent and have distinct functions which reside in the
      extracellular domains.

PMID- 9250664
TI  - The three-dimensional structure of a T-cell antigen receptor V alpha V beta
      heterodimer reveals a novel arrangement of the V beta domain.
AB  - The crystal structure of a mouse T-cell antigen receptor (TCR) Fv fragment
      complexed to the Fab fragment of a specific anti-clonotypic antibody has been
      determined to 2.6 A resolution. The polypeptide backbone of the TCR V alpha
      domain is very similar to those of other crystallographically determined V
      alphas, whereas the V beta structure is so far unique among TCR V beta domains in
      that it displays a switch of the c" strand from the inner to the outer beta
      sheet. The beta chain variable region of this TCR antigen-binding site is
      characterized by a rather elongated third complementarity-determining region
      (CDR3beta) that packs tightly against the CDR3 loop of the alpha chain, without
      leaving any intervening hydrophobic pocket. Thus, the conformation of the CDR
      loops with the highest potential diversity distinguishes the structure of this
      TCR antigen-binding site from those for which crystallographic data are
      available. On the basis of all these results, we infer that a significant
      conformational change of the CDR3beta loop found in our TCR is required for
      binding to its cognate peptide-MHC ligand.

PMID- 9250663
TI  - Suppressors of YCK-encoded yeast casein kinase 1 deficiency define the four
      subunits of a novel clathrin AP-like complex.
AB  - In Saccharomyces cerevisiae, the redundant YCK1 and YCK2 genes (Yeast Casein
      Kinase 1) are required for viability. We describe here the molecular analysis of
      four mutations that eliminate the requirement for Yck activity. These mutations
      alter proteins that resemble the four subunits of clathrin adaptors (APs), with
      highest sequence similarity to those of the recently identified AP-3 complex. The
      four yeast subunits are associated in a high-molecular-weight complex. These
      proteins have no essential function and are not redundant for function with other
      yeast AP-related proteins. Combination of suppressor mutations with a clathrin
      heavy chain mutation (chc1-ts) confers no synthetic growth defects. However, a
      yck(ts) mutation shows a strong synthetic growth defect with chc1-ts. Moreover,
      endocytosis of Ste3p is dramatically decreased in yck(ts) cells and is partially
      restored by the AP suppressor mutations. These results suggest that vesicle
      trafficking at the plasma membrane requires the activity of Yck protein kinases,
      and that the new AP-related complex may participate in this process.

PMID- 9250665
TI  - Normal development but differentially altered proliferative responses of
      lymphocytes in mice lacking CD81.
AB  - CD81 (TAPA-1) is a member of the transmembrane 4 superfamily (TM4SF) which is
      expressed on the cell surface of most cells of the body throughout their cellular
      differentiation. It has been recognized in several cell surface complexes of
      lymphocytes, suggesting that it may have diverse roles in lymphocyte development
      and activation regulation. Mice with a CD81 null mutation revealed normal T- and
      conventional B-cell development, although CD19 expression on B cells was dull and
      B-1 cells were reduced in number. However, both T and B cells of mutant mice
      exhibited strikingly enhanced proliferation in response to various types of
      stimuli. Interestingly, while proliferative responses of T cells following T-cell
      antigen receptor (TCR) engagement was enhanced in the absence of CD81, B-cell
      proliferation in response to B-cell antigen-receptor (BCR) cross-linking was
      severely impaired. Despite these altered proliferative responses, both tyrosine
      phosphorylation and intracellular calcium flux in response to cross-linking of
      cell surface antigen receptors were normal in mutant mice, reflecting apparently
      normal initial signaling of antigen receptors. In conclusion, though CD81 is not
      essential for normal T- and conventional B-cell development, it plays key roles
      in controlling lymphocyte homeostasis by regulating lymphocyte proliferation in
      distinct manners, dependent on the context of stimulation.

PMID- 9250666
TI  - Immortalization and leukemic transformation of a myelomonocytic precursor by
      retrovirally transduced HRX-ENL.
AB  - A subset of chromosomal translocations in acute leukemias results in the fusion
      of the trithorax-related protein HRX with a variety of heterologous proteins. In
      particular, leukemias with the t(11;19)(q23;p13.3) translocation express HRX-ENL
      fusion proteins and display features which suggest the malignant transformation
      of myeloid and/or lymphoid progenitor(s). To characterize directly the potential
      transforming effects of HRX-ENL on primitive hematopoietic precursors, the fusion
      cDNA was transduced by retroviral gene transfer into cell populations enriched in
      hematopoietic stem cells. The infected cells had a dramatically enhanced
      potential to generate myeloid colonies with primitive morphology in vitro.
      Primary colonies could be replated for at least three generations in vitro and
      established primitive myelomonocytic cell lines upon transfer into suspension
      cultures supplemented with interleukin-3 and stem cell factor. Immortalized cells
      contained structurally intact HRX-ENL proviral DNA and expressed a low-level of
      HRX-ENL mRNA. In contrast, wild-type ENL or a deletion mutant of HRX-ENL lacking
      the ENL component did not demonstrate in vitro transforming capabilities.
      Immortalized cells or enriched primary hematopoietic stem cells transduced with
      HRX-ENL induced myeloid leukemias in syngeneic and SCID recipients. These studies
      demonstrate a direct role for HRX-ENL in the immortalization and leukemic
      transformation of a myeloid progenitor and support a gain-of-function mechanism
      for HRX-ENL-mediated leukemogenesis.

PMID- 9250668
TI  - The gamma subunit is a specific component of the Na,K-ATPase and modulates its
      transport function.
AB  - The role of small, hydrophobic peptides that are associated with ion pumps or
      channels is still poorly understood. By using the Xenopus oocyte as an expression
      system, we have characterized the structural and functional properties of the
      gamma peptide which co-purifies with Na,K-ATPase. Immuno-radiolabeling of epitope
      tagged gamma subunits in intact oocytes and protease protection assays show that
      the gamma peptide is a type I membrane protein lacking a signal sequence and
      exposing the N-terminus to the extracytoplasmic side. Co-expression of the rat or
      Xenopus gamma subunit with various proteins in the oocyte reveals that it
      specifically associates only with isozymes of Na,K-ATPase. The gamma peptide does
      not influence the formation and cell surface expression of functional Na,K-ATPase
      alpha-beta complexes. On the other hand, the gamma peptide itself needs
      association with Na,K-ATPase in order to be stably expressed in the oocyte and to
      be transported efficiently to the plasma membrane. Gamma subunits do not
      associate with individual alpha or beta subunits but only interact with
      assembled, transport-competent alpha-beta complexes. Finally,
      electrophysiological measurements indicate that the gamma peptide modulates the
      K+ activation of Na,K pumps. These data document for the first time the membrane
      topology, the specificity of association and a potential functional role for the
      gamma subunit of Na,K-ATPase.

PMID- 9250667
TI  - Complementation of null CF mice with a human CFTR YAC transgene.
AB  - We have made transgenic mice carrying a 320 kb YAC with the intact human cystic
      fibrosis transmembrane regulator (CFTR) gene. Mice that only express the human
      transgene were obtained by breeding with Cambridge null CF mice. One line has
      approximately two copies of the intact YAC. Mice carrying this transgene and
      expressing no mouse cftr appear normal and breed well, in marked contrast to the
      null mice, where 50% die by approximately 5 days after birth. The chloride
      secretory responses in these mice are as large or larger than in wild-type
      tissues. Expression of the transgene is highly cell type specific and matches
      that of the endogenous mouse gene in the crypt epithelia throughout the gut and
      in salivary gland tissue. However, there is no transgene expression in some
      tissues, such as the Brunner's glands, where it would be expected. Where there
      are differences between the mouse and human pattern of expression, the transgene
      follows the mouse pattern. We have thus defined a cloned fragment of DNA which
      directs physiological levels of expression in many of the specific cells where
      CFTR is normally expressed.

PMID- 9250669
TI  - Anionic phospholipids are determinants of membrane protein topology.
AB  - The orientation of many membrane proteins is determined by the asymmetric
      distribution of positively charged amino acid residues in cytoplasmic and
      translocated loops. The positive-inside rule states that loops with large amounts
      of these residues tend to have cytoplasmic locations. Orientations of constructs
      derived from the inner membrane protein leader peptidase from Escherichia coli
      were found to depend on the anionic phospholipid content of the membrane.
      Lowering the contents of anionic phospholipids facilitated membrane passage of
      positively charged loops. On the other hand, elevated contents of acidic
      phospholipids in the membrane rendered translocation more sensitive to positively
      charged residues. The results demonstrate that anionic lipids are determinants of
      membrane protein topology and suggest that interactions between negatively
      charged phospholipids and positively charged amino acid residues contribute to
      the orientation of membrane proteins.

PMID- 9250670
TI  - Binding of mitochondrial precursor proteins to the cytoplasmic domains of the
      import receptors Tom70 and Tom20 is determined by cytoplasmic chaperones.
AB  - We have reconstituted the early steps of precursor targeting to mitochondria in a
      defined and soluble system consisting of the cytosolic domains of the yeast
      mitochondrial import receptors Tom20 and Tom70, precursor to bovine adrenal
      adrenodoxin (which has a cleavable targeting signal) and rat liver cytosolic
      chaperones hsp70 and mitochondrial import-stimulating factor (MSF). The Tom70
      domain only bound the precursor in the presence of MSF, yielding a precursor-MSF
      Tom70 complex; ATP hydrolysis by MSF released MSF and generated a precursor-Tom70
      complex whose formation was inhibited by an excess of a functional presequence
      peptide, but not by 150 mM NaCl. In the presence of the Tom20 domain, ATP caused
      transfer of the precursor from the precursor-MSF-Tom70 complex to Tom20. The
      Tom20 domain alone only bound the precursor in the presence of hsp70; hsp70
      itself was not incorporated into the resulting complex. Formation of the Tom20
      precursor complex was inhibited by excess presequence peptide or by 150 mM NaCl.
      Similar results were obtained with the ADP/ATP carrier and porin precursors,
      which both lack a cleaved targeting signal. Correct targeting of a precursor to
      mitochondrial import receptors thus requires cytosolic chaperones, irrespective
      of the presence or absence of a cleavable presequence.

PMID- 9250671
TI  - Nuclear export of the E1B 55-kDa and E4 34-kDa adenoviral oncoproteins mediated
      by a rev-like signal sequence.
AB  - The E1B 55-kDa and E4 34-kDa oncoproteins of adenovirus type 5 (abbreviated here
      as E1B-55kD and E4-34kD) promote the export of viral mRNA and inhibit the export
      of most cellular mRNA species. We show that the intracellular complex containing
      E1B-55kD and E4-34kD continuously shuttles between the nucleus and the cytoplasm,
      and may thus serve as a nucleocytoplasmic transporter for viral mRNA. We present
      evidence that within this complex, it is the E4-34kD protein that directs both
      nuclear import and nuclear export. E4-34kD contains a functional nuclear export
      signal similar to corresponding sequences found in the retroviral proteins rev
      and rex. This sequence element is required for nuclear export of the complex, and
      it can function autonomously when fused to a carrier protein and microinjected in
      HeLa cell nuclei. When E4-34kD is expressed alone, a portion of the protein that
      contains a predicted arginine-rich amphipathic alpha-helical structure mediates
      nuclear retention of the protein. This retention, however, can be abolished by
      the association with E1B-55kD or by a specific point mutation within the arginine
      rich motif. The export of E4-34kD can be blocked by an HTLV-rex derived
      competitive inhibitor and overexpressed E4-34kD inhibits rev-mediated transport,
      suggesting that the export pathways accessed by the adenoviral and retroviral
      proteins share components. The interplay between two polypeptides as well as the
      involvement of a dominant nuclear retention domain are novel features that might
      contribute to the efficiency and regulation of the adenovirus export system.

PMID- 9250672
TI  - Expression of bloodstream variant surface glycoproteins in procyclic stage
      Trypanosoma brucei: role of GPI anchors in secretion.
AB  - Using transformed procyclic trypanosomes, the synthesis, intracellular transport
      and secretion of wild-type and mutant variant surface glycoprotein (VSG) is
      characterized. We find no impediment to the expression of this bloodstream stage
      protein in insect stage cells. VSG receives a procyclic-type phosphatidylinositol
      specific phospholipase C-resistant glycosyl phosphatidylinositol (GPI) anchor,
      dimerizes and is N-glycosylated. It is transported to the plasma membrane with
      rapid kinetics (t(1/2) approximately 1 h) and then released by a cell surface
      zinc-dependent metalloendoprotease activity, a possible homolog of leishmanial
      gp63. Deletion of the C-terminal GPI addition signal generates a soluble form of
      VSG that is exported with greatly reduced kinetics (t(1/2) approximately 5 h).
      Fusion of the procyclic acidic repetitive protein (PARP) GPI anchor signal to the
      C-terminus of the truncated VSG reporter restores both GPI addition and transport
      competence, suggesting that GPI anchors play a critical role in the folding
      and/or forward transport of newly synthesized VSG. The VSG-PARP fusion is also
      processed near the C-terminus by events that do not involve N-linked
      oligosaccharides and which are consistent with GPI side chain modification. This
      unexpected result suggests that GPI processing may be influenced by adjacent
      peptide sequence or conformation.

PMID- 9250673
TI  - Folding of a bacterial outer membrane protein during passage through the
      periplasm.
AB  - The transport of bacterial outer membrane proteins to their destination might be
      either a one-step process via the contact zones between the inner and outer
      membrane or a two-step process, implicating a periplasmic intermediate that
      inserts into the membrane. Furthermore, folding might precede insertion or vice
      versa. To address these questions, we have made use of the known 3D-structure of
      the trimeric porin PhoE of Escherichia coli to engineer intramolecular disulfide
      bridges into this protein at positions that are not exposed to the periplasm once
      the protein is correctly assembled. The mutations did not interfere with the
      biogenesis of the protein, and disulfide bond formation appeared to be dependent
      on the periplasmic enzyme DsbA, which catalyzes disulfide bond formation in the
      periplasm. This proves that the protein passes through the periplasm on its way
      to the outer membrane. Furthermore, since the disulfide bonds create elements of
      tertiary structure within the mutant proteins, it appears that these proteins are
      at least partially folded before they insert into the outer membrane.

PMID- 9250674
TI  - The solution NMR structure of glucosylated N-glycans involved in the early stages
      of glycoprotein biosynthesis and folding.
AB  - Glucosylated oligomannose N-linked oligosaccharides (Glc(x)Man9GlcNAc2 where x =
      1-3) are not normally found on mature glycoproteins but are involved in the early
      stages of glycoprotein biosynthesis and folding as (i) recognition elements
      during protein N-glycosylation and chaperone recognition and (ii) substrates in
      the initial steps of N-glycan processing. By inhibiting the first steps of glycan
      processing in CHO cells using the alpha-glucosidase inhibitor N-butyl
      deoxynojirimycin, we have produced sufficient Glc3Man7GlcNAc2 for structural
      analysis by nuclear magnetic resonance (NMR) spectroscopy. Our results show the
      glucosyl cap to have a single, well-defined conformation independent of the rest
      of the saccharide. Comparison with the conformation of Man9GlcNAc2, previously
      determined by NMR and molecular dynamics, shows the mannose residues to be
      largely unaffected by the presence of the glucosyl cap. Sequential enzymatic
      cleavage of the glucose residues does not affect the conformation of the
      remaining saccharide. Modelling of the Glc3Man9GlcNAc2, Glc2Man9GlcNAc2 and
      Glc1Man9GlcNAc2 conformations shows the glucose residues to be fully accessible
      for recognition. A more detailed analysis of the conformations allows potential
      recognition epitopes on the glycans to be identified and can form the basis for
      understanding the specificity of the glucosidases and chaperones (such as
      calnexin) that recognize these glycans, with implications for their mechanisms of
      action.

PMID- 9250675
TI  - Elucidation of the subunit orientation in CCT (chaperonin containing TCP1) from
      the subunit composition of CCT micro-complexes.
AB  - A collection of chaperonin containing TCP1 (CCT) micro-complexes that are
      comprised of subsets of the constitutively expressed CCT subunits have been
      identified. These CCT micro-complexes have mol. wts ranging from 120 to 250 kDa
      and are present in cells at lower abundance (<5%) as compared with intact CCT.
      Biochemical characterization of these microcomplexes has shown that several are
      comprised of two different types of CCT subunit. Furthermore, it was observed
      that each subunit associates with only one or two other different types of
      subunit, suggesting that each subunit has fixed partners. This observation,
      together with CCT gene counting being concordant with the 8-fold structural
      symmetry, is consistent with predictions derived from analysis of the primary
      structures of these subunits concerning inter-subunit interactions, and implies a
      unique topology of the subunits constituting the torodial ring in CCT. The series
      of subunit-subunit association patterns determined from CCT micro-complexes has
      provided information to infer, from the 5040 (7!factorial) combinatorial
      possibilities, one probable subunit orientation within the torodial ring.

PMID- 9250676
TI  - The Dictyostelium MAP kinase kinase DdMEK1 regulates chemotaxis and is essential
      for chemoattractant-mediated activation of guanylyl cyclase.
AB  - We have identified a MAP kinase kinase (DdMEK1) that is required for proper
      aggregation in Dictyostelium. Null mutations produce extremely small aggregate
      sizes, resulting in the formation of slugs and terminal fruiting bodies that are
      significantly smaller than those of wild-type cells. Time-lapse video microscopy
      and in vitro assays indicate that the cells are able to produce cAMP waves that
      move through the aggregation domains. However, these cells are unable to undergo
      chemotaxis properly during aggregation in response to the chemoattractant cAMP or
      activate guanylyl cyclase, a known regulator of chemotaxis in Dictyostelium. The
      activation of guanylyl cyclase in response to osmotic stress is, however, normal.
      Expression of putative constitutively active forms of DdMEK1 in a ddmek1 null
      background is capable, at least partially, of complementing the small aggregate
      size defect and the ability to activate guanylyl cyclase. However, this does not
      result in constitutive activation of guanylyl cyclase, suggesting that DdMEK1
      activity is necessary, but not sufficient, for cAMP activation of guanylyl
      cyclase. Analysis of a temperature-sensitive DdMEK1 mutant suggests that DdMEK1
      activity is required throughout aggregation at the time of guanylyl cyclase
      activation, but is not essential for proper morphogenesis during the later
      multicellular stages. The activation of the MAP kinase ERK2, which is essential
      for chemoattractant activation of adenylyl cyclase, is not affected in ddmek1
      null strains, indicating that DdMEK1 does not regulate ERK2 and suggesting that
      at least two independent MAP kinase cascades control aggregation in
      Dictyostelium.

PMID- 9250677
TI  - MAP kinase links the fertilization signal transduction pathway to the G1/S-phase
      transition in starfish eggs.
AB  - The mechanism by which fertilization initiates S-phase in the zygote is examined
      by manipulating the activity of MAP kinase in mature starfish eggs. These
      unfertilized eggs, which are arrested at G1-phase after the completion of
      meiosis, have high MAP kinase activity but undetectable cdc2 kinase activity.
      Either fertilization or inhibition of protein synthesis causes a decrease in MAP
      kinase activity, which is followed by DNA synthesis. Inactivation of MAP kinase
      with its specific phosphatase, CL100, initiates DNA synthesis in the absence of
      fertilization, while constitutive activation of MAP kinase with MEK represses the
      initiation of DNA synthesis following fertilization. Thus, in unfertilized mature
      starfish eggs, a capacity for DNA replication is already acquired, but entry into
      S-phase is negatively regulated by MAP kinase activity that is supported by a
      continuously synthesized protein(s) but not by cdc2 kinase. Upon fertilization,
      downregulation of MAP kinase activity is necessary and sufficient for triggering
      the G1/S-phase transition.

PMID- 9250678
TI  - Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro
      phosphorylation of MCM subunits by a putative human homologue of Cdc7.
AB  - Saccharomyces cerevisiae Cdc7 kinase is essential for initiation of DNA
      replication, and Hsk1, a related kinase of Schizosaccharomyces pombe, is also
      required for DNA replication of fission yeast cells. We report here cDNAs
      encoding Cdc7-related kinases from human and Xenopus (huCdc7 and xeCdc7,
      respectively). The cloned cDNA for huCdc7 contains an open reading frame
      consisting of 574 amino acids with a predicted molecular weight of 63,847 that
      possesses overall amino acid identity of 32% (54% including similar residues) to
      Cdc7 and Hsk1. huCDC7 is transcribed in the various tissues examined, but most
      abundantly in testis. Three transcripts of 4.4, 3.5 and 2.4 kb in length are
      detected. The 3.5 kb transcript is the most predominant and is expressed in all
      the tissues examined. A cDNA containing a 91 nucleotide insertion at the N
      terminal region of huCDC7 is also detected, suggesting the presence of multiple
      splicing variants. The huCdc7 protein is expressed at a constant level during the
      mitotic cell cycle and is localized primarily in nuclei in interphase and
      distributed diffusibly in cytoplasm in the mitotic phase. The wild-type huCdc7
      protein expressed in COS7 cells phosphorylates MCM2 and MCM3 proteins in vitro,
      suggesting that huCdc7 may regulate processes of DNA replication by modulating
      MCM functions.

PMID- 9250679
TI  - Cell type-specific chromatin organization of the region that governs
      directionality of yeast mating type switching.
AB  - Switching of mating type in Saccharomyces cerevisiae is directional; MAT alpha
      cells recombine to transfer information from HMRa while MATa cells switch using
      the silent cassette at HML alpha. Genetic analysis recently has defined a 700 bp
      recombination enhancer approximately 29 kb from the left end of chromosome III
      that is necessary for directionality. The chromatin structure of this region
      differs strikingly in a- and alpha-cells. Mat alpha2p organizes a 3.7 kb
      chromatin domain that opposes interaction of trans-acting proteins with the
      enhancer. In a-cells lacking the alpha2 repressor, two footprinted regions flank
      an approximately 100 bp section having a unique DNA structure. This structural
      signature probably reflects interactions of proteins that result in directional
      mating type switching.

PMID- 9250680
TI  - Remodeling of regulatory nucleoprotein complexes on the Xenopus hsp70 promoter
      during meiotic maturation of the Xenopus oocyte.
AB  - Transcriptional repression occurs during meiotic maturation of Xenopus oocytes.
      Injection of a DNA template containing an hsp70 promoter into Xenopus oocytes,
      followed by progesterone-induced maturation has been used to demonstrate a
      dynamic competition between the assembly of transcription factor-containing
      nucleoprotein complexes and repressive nucleosomal arrays during the maturation
      process. In particular, it is shown that increased levels of injected heat shock
      protein, the transcriptional activator Gal4-VP16 or the DNA template itself all
      lead to reduced repression of transcription on maturation. Conversely, injection
      of additional histone increases repression. Repression of transcription is shown
      to be accompanied by the formation of a more regular array of nucleosomes and by
      an increase in the efficiency of nucleosome assembly on the injected plasmid.
      Meiotic maturation is therefore accompanied by replacement of transcription
      factor complexes by a repressive chromatin environment.

PMID- 9250681
TI  - Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets
      related factor TEL.
AB  - The TEL gene, which is frequently rearranged in human leukemias of both myeloid
      and lymphoid origin, encodes a member of the Ets family of transcription factors.
      The TEL gene is widely expressed throughout embryonic development and in the
      adult. To determine the requirement for the TEL gene product in development we
      generated TEL knockout mice (TEL-/-) by gene targeting in embryonic stem cells.
      TEL-/- mice are embryonic lethal and die between E10.5-11.5 with defective yolk
      sac angiogenesis and intra-embryonic apoptosis of mesenchymal and neural cells.
      Two-thirds of TEL-deficient yolk sacs at E9.5 lack vitelline vessels, yet possess
      capillaries, indicative of normal vasculogenesis. Vitelline vessels regress by
      E10.5 in the remaining TEL-/- yolk sacs. Hematopoiesis at the yolk sac stage,
      however, appears unaffected in TEL-/- embryos. Our findings demonstrate that TEL
      is required for maintenance of the developing vascular network in the yolk sac
      and for survival of selected cell types within the embryo proper.

PMID- 9250682
TI  - A novel p53-inducible gene, PAG608, encodes a nuclear zinc finger protein whose
      overexpression promotes apoptosis.
AB  - The biological effects of the p53 tumor suppressor protein are elicited, at least
      in part, through sequence-specific transactivation of a battery of target genes.
      The differential display method was employed towards identifying additional p53
      target genes, with emphasis on genes whose induction may contribute to p53
      mediated apoptosis. We report here the cloning of a novel p53-inducible gene,
      designated PAG608. PAG608 transcripts are induced by DNA damage in a p53
      dependent manner. PAG608 encodes a nuclear zinc finger protein, which appears to
      localize preferentially to nucleoli when expressed at moderate levels in
      transfected cells. Transient overexpression of PAG608 in human tumor-derived
      cells leads to distinctive changes in nuclear morphology, and can promote
      apoptosis. Together with additional p53 target genes, PAG608 may therefore play a
      role in mediating the biological activities of p53.

PMID- 9250683
TI  - Deletion of a HoxD enhancer induces transcriptional heterochrony leading to
      transposition of the sacrum.
AB  - A phylogenetically conserved transcriptional enhancer necessary for the
      activation of Hoxd-11 was deleted from the HoxD complex of mice by targeted
      mutagenesis. While genetic and expression analyses demonstrated the role of this
      regulatory element in the activation of Hoxd-11 during early somitogenesis, the
      function of this gene in developing limbs and the urogenital system was not
      affected, suggesting that Hox transcriptional controls are different in different
      axial structures. In the trunk of mutant embryos, transcriptional activation of
      Hoxd-11 and Hoxd-10 was severely delayed, but subsequently resumed with
      appropriate spatial distributions. The resulting caudal transposition of the
      sacrum indicates that proper vertebral specification requires a precise temporal
      control of Hox gene expression, in addition to spatial regulation. A slight time
      delay in expression (transcriptional heterochrony) cannot be compensated for at a
      later developmental stage, eventually leading to morphological alterations.

PMID- 9250684
TI  - Mechanism and Bicoid-dependent control of hairy stripe 7 expression in the
      posterior region of the Drosophila embryo.
AB  - Pair-rule gene hairy (h) expression in seven evenly spaced stripes, along the
      longitudinal axis of the Drosophila blastoderm embryo, is mediated by a modular
      array of separate stripe enhancer elements. The minimal enhancer element, which
      generates reporter gene expression in place of the most posterior h stripe 7 (h7
      element), contains a dense array of binding sites for factors providing the trans
      acting control of h stripe 7 expression as revealed by genetic analyses. The h7
      element mediates position-dependent gene expression by sensing region-specific
      combinations and concentrations of both the maternal homeodomain transcriptional
      activators, Caudal and Bicoid, and of transcriptional repressors encoded by
      locally expressed zygotic gap genes. Caudal and Bicoid, which form complementing
      concentration gradients along the longitudinal axis of the embryo, function as
      redundant activators, indicating that the anterior determinant Bicoid is able to
      activate gene expression in the most posterior region of the embryo. The spatial
      limits of the h stripe-7 domain are brought about by the local activities of
      repressors which prevent activation. The results suggest that the gradients of
      Bicoid and Caudal combine their activities to activate segmentation genes along
      the entire axis of the embryo.

PMID- 9250685
TI  - The T3R alpha gene encoding a thyroid hormone receptor is essential for post
      natal development and thyroid hormone production.
AB  - The diverse functions of thyroid hormones are thought to be mediated by two
      nuclear receptors, T3R alpha1 and T3R beta, encoded by the genes T3R alpha and
      T3R beta respectively. The T3R alpha gene also produces a non-ligand-binding
      protein T3R alpha2. The in vivo functions of these receptors are still unclear.
      We describe here the homozygous inactivation of the T3R alpha gene which
      abrogates the production of both T3R alpha1 and T3R alpha2 isoforms and that
      leads to death in mice within 5 weeks after birth. After 2 weeks of life, the
      homozygous mice become progressively hypothyroidic and exhibit a growth arrest.
      Small intestine and bones showed a strongly delayed maturation. In contrast to
      the negative regulatory function of the T3R beta gene on thyroid hormone
      production, our data show that the T3R alpha gene products are involved in up
      regulation of thyroid hormone production at weaning time. Thus, thyroid hormone
      production might be balanced through a positive T3R alpha and a negative T3R beta
      pathway. The abnormal phenotypes observed on the homozygous mutant mice strongly
      suggest that the T3R alpha gene is essential for the transformation of a mother
      dependent pup to an 'adult' mouse. These data define crucial in vivo functions
      for thyroid hormones through a T3R alpha pathway during post-natal development.

PMID- 9250686
TI  - Identification of a human protein that recognizes the 3' splice site during the
      second step of pre-mRNA splicing.
AB  - Accurate splicing of precursor mRNAs (pre-mRNAs) requires recognition of the 5'
      and 3' splice sites at the intron boundaries. Interactions between several
      splicing factors and the 5' splice site, which occur prior to the first step of
      splicing, have been well described. In contrast, recognition of the 3' splice
      site, which is cleaved during the second catalytic step, is poorly understood,
      particularly in higher eukaryotes. Here, using site-specific photo-crosslinking,
      we find that the conserved AG dinucleotide at the 3' splice site is contacted
      specifically by a 70 kDa polypeptide (p70). The p70-3' splice site crosslink has
      kinetics and biochemical requirements similar to those of splicing, was detected
      only in the mature spliceosome and occurs subsequent to the first step. Thus, p70
      has all the properties expected of a factor that functionally interacts with the
      3' splice site during the second step of splicing. Using antisera to various
      known splicing factors, we find that p70 corresponds to a previously reported 69
      kDa protein of unknown function associated with the Sm core domain of
      spliceosomal small nuclear ribonucleoproteins.

PMID- 9250687
TI  - Trans mRNA splicing in trypanosomes: cloning and analysis of a PRP8-homologous
      gene from Trypanosoma brucei provides evidence for a U5-analogous RNP.
AB  - In trypanosomes all mRNAs are generated through trans mRNA splicing, requiring
      the functions of the small nuclear RNAs U2, U4 and U6. In the absence of
      conventional cis mRNA splicing, the structure and function of a U5-analogous
      snRNP in trypanosomes has remained an open question. In cis splicing, a U5 snRNP
      specific protein component called PRP8 in yeast and p220 in man is a highly
      conserved, essential splicing factor involved in splice-site recognition and
      selection. We have cloned and sequenced a genomic region from Trypanosoma brucei,
      that contains a PRP8/p220-homologous gene (p277) coding for a 277 kDa protein.
      Using an antibody against a C-terminal region of the trypanosomal p277 protein, a
      small RNA of approximately 65 nucleotides could be specifically co
      immunoprecipitated that appears to be identical with a U5 RNA (SLA2 RNA) recently
      identified by Dungan et al. (1996). Based on sedimentation, immunoprecipitation
      and Western blot analyses we conclude that this RNA is part of a stable
      ribonucleoprotein (RNP) complex and associated not only with the p277 protein,
      but also with the common proteins present in the other trans-spliceosomal snRNPs.
      Together these results demonstrate that a U5-analogous RNP exists in trypanosomes
      and suggest that basic functions of the U5 snRNP are conserved between cis and
      trans splicing.

PMID- 9250688
TI  - Reprogramming the purine nucleotide cofactor requirement of Drosophila P element
      transposase in vivo.
AB  - Guanosine triphosphate (GTP)-binding proteins are involved in controlling a wide
      range of fundamental cellular processes. In vitro studies have indicated a role
      for GTP during Drosophila P element transposition. Here we show that P element
      transposase contains a non-canonical GTP-binding domain that is critical for its
      ability to mediate transposition in Drosophila cells. Moreover, a single amino
      acid substitution could switch the nucleotide binding-specificity of transposase
      from GTP to xanthosine triphosphate (XTP). Importantly, this mutant protein could
      no longer function effectively in transposition in vivo but required addition of
      exogenous xanthine or xanthosine for reactivation. These results suggest that
      transposition may be controlled by physiological GTP levels and demonstrate that
      a single mutation can switch the nucleotide specificity for a complex cellular
      process in vivo.

PMID- 9250689
TI  - A LINE-like transposable element in Drosophila, the I factor, encodes a protein
      with properties similar to those of retroviral nucleocapsids.
AB  - I factors are members of the LINE-like family of transposable elements and move
      by reverse transcription of an RNA intermediate. Complete I factors contain two
      open reading frames. The amino acid sequence encoded by the first of these, ORF1,
      includes the motif CX2CX4HX4C that is characteristic of the nucleocapsid domain
      of retroviral gag polypeptides followed by a copy of the slightly different
      sequences CX2CX4HX6C and CX2CX9HX6C. The function of this protein is unknown. We
      have expressed this protein in Escherichia coli and Spodoptera frugiperda cells
      and have shown that it binds both DNA and RNA but without any evidence for
      sequence specificity. The properties of deletion derivatives of the protein
      indicate that more than one region is responsible for DNA binding and that the
      CCHC motif is not essential for this. The ORF1 protein expressed in either E.
      coli or Spodoptera cells forms high molecular weight structures that require the
      region of the protein including the CCHC motif for their formation. This protein
      can also accelerate the annealing of complementary single-stranded
      oligonucleotides. These results suggest that this protein may associate with the
      RNA transposition intermediates of the I factor to form particles that enter the
      nucleus during transposition and that it may stimulate both the priming of
      reverse transcription and integration. This may be generally true for the product
      of the first open reading frame of LINE-like elements.

PMID- 9250690
TI  - Why is the initiation nick site of an AT-rich rolling circle plasmid at the tip
      of a GC-rich cruciform?
AB  - pT181 and other closely related rolling circle plasmids have the nicking site for
      initiation of replication between the arms of a GC-rich inverted repeat sequence
      adjacent to the binding site for the dimeric initiator protein. Replication is
      initiated by the initiator-induced extrusion of this sequence as a cruciform,
      creating a single-stranded region for nicking by the protein. Nicking is followed
      by assembly of the replisome without relaxation of the secondary structure.
      Following termination, the initiator protein is released with a short
      oligonucleotide attached to one subunit, which prevents it from being recycled, a
      necessary feature of the plasmid's replication control system. The modified
      initiator can cleave single-stranded substrates and can nick and relax
      supercoiled plasmid DNA weakly. Although it can bind to its recognition sequence
      in the leading strand origin, the modified protein cannot induce cruciform
      extrusion, and it is proposed that this inability is the key to understanding the
      biological rationale for having the nicking site at the tip of a cruciform: the
      need to provide the functional initiator with a catalytic advantage over the
      modified one sufficient to offset the numerical advantage and metabolic stability
      of the latter.

PMID- 9250692
TI  - Intermediates in the assembly pathway of the double-stranded RNA virus phi6.
AB  - The double-stranded RNA bacteriophage phi6 contains a nucleocapsid enclosed by a
      lipid envelope. The nucleocapsid has an outer layer of protein P8 and a core
      consisting of the four proteins P1, P2, P4 and P7. These four proteins form the
      polyhedral structure which acts as the RNA packaging and polymerase complex.
      Simultaneous expression of these four proteins in Escherichia coli gives rise to
      procapsids that can carry out the entire RNA replication cycle. Icosahedral image
      reconstruction from cryo-electron micrographs was used to determine the three
      dimensional structures of the virion-isolated nucleocapsid and core, and of
      several procapsid-related particles expressed and assembled in E. coli. The
      nucleocapsid has a T = 13 surface lattice, composed primarily of P8. The core is
      a rounded structure with turrets projecting from the 5-fold vertices, while the
      procapsid is smaller than the core and more dodecahedral. The differences between
      the core and the procapsid suggest that maturation involves extensive structural
      rearrangements producing expansion. These rearrangements are co-ordinated with
      the packaging and RNA polymerization reactions that result in virus assembly.
      This structural characterization of the phi6 assembly intermediates reveals the
      ordered progression of obligate stages leading to virion assembly along with
      striking similarities to the corresponding Reoviridae structures.

PMID- 9250691
TI  - MutS mediates heteroduplex loop formation by a translocation mechanism.
AB  - Interaction of Escherichia coli MutS and MutL with heteroduplex DNA has been
      visualized by electron microscopy. In a reaction dependent on ATP hydrolysis,
      complexes between a MutS dimer and a DNA heteroduplex are converted to protein
      stabilized, alpha-shaped loop structures with the mismatch in most cases located
      within the DNA loop. Loop formation depends on ATP hydrolysis and loop size
      increases linearly with time at a rate of 370 base pairs/min in phosphate buffer
      and about 10,000 base pairs/min in the HEPES buffer used for repair assay. These
      observations suggest a translocation mechanism in which a MutS dimer bound to a
      mismatch subsequently leaves this site by ATP-dependent tracking or
      unidimensional movement that is in most cases bidirectional from the mispair. In
      view of the bidirectional capability of the methyl-directed pathway, this
      reaction may play a role in determination of heteroduplex orientation. The rate
      of MutS-mediated DNA loop growth is enhanced by MutL, and when both proteins are
      present, both are found at the base of alpha-loop structures, and both can remain
      associated with excision intermediates produced in later stages of the reaction.

PMID- 9250693
TI  - Prostaglandins in primate semen: biasing the immune system to benefit spermatozoa
      and virus?
AB  - The levels of prostaglandins in human semen are many orders of magnitude higher
      than those found elsewhere in the body and semen contains 19-hydroxy PGE which
      has not been found in other tissues. The reason for the presence of these
      prostaglandins is now becoming apparent with the demonstration of powerful
      effects of PGE and 19-hydroxy PGE on the balance of cytokines (stimulating IL-10
      and inhibiting IL-12) released by antigen presenting cells. The effects of the
      seminal prostaglandins will be two-fold. First, there will be cAMP mediated
      direct effect on T cells, inhibiting clonal proliferation, inhibiting natural
      killer cell function and biasing the CD4 cells to a T-helper-2 pattern of
      cytokine production away from one that would favour a cell-mediated response.
      Second, and perhaps the major effect, is at the level of the antigen presenting
      cell that will reinforce the direct effects and induce a tolerance of antigens
      that are presented together with the IL-10, or PGE. Such tolerance might be
      necessary for the survival of the spermatozoa under adverse conditions, for
      instance, in the presence of infection Viruses and other invading organisms would
      also benefit from this switch in cytokines and the inhibition of the cell
      mediated defences. Particular concerns are human immunodeficiency virus (HIV) and
      human papilloma virus (HPV) which can be transmitted in semen. Not only will the
      initial immune response be affected, but also repeated exposure to semen will
      reduce immunesurveillance and the removal of virally infected cells.

PMID- 9250694
TI  - Role of cytosolic phospholipase A2 in eicosanoid generation by corpora lutea of
      pseudopregnant rats: effects of its specific inhibitor.
AB  - This study was performed to investigate whether 85 kDa cytosolic phospholipase A2
      (cPLA2) functions in eicosanoid generation in rat corpora lutea (CL) using its
      specific inhibitor, arachidonyl trifluoromethyl ketone (ATK). In both immature
      and adult pseudopregnant rats, PLA2 activity in the cytosol of CL, measured by
      the liposome-vesicle assay, increased from day 6 of pseudopregnancy (PSP6) to
      PSP12. 10 microM ATK potently inhibited all of these activities to 10-20% and the
      rate of the inhibition by ATK was much higher on PSP12. ATK also reduced
      arachidonic acid (AA) release from luteal cells of PSP12 prelabelled with 3H-AA.
      Furthermore, the production of prostaglandin E2 by cultured luteal cells was
      mostly suppressed by the drug. These results suggest the augmentation of cPLA2
      activity with the luteal age of pseudopregnant rats and its principal role in
      eicosanoid generation in CL.

PMID- 9250695
TI  - Effects of dietary gamma-linolenic acid-rich borage oil combined with marine fish
      oils on tissue phospholipid fatty acid composition and production of
      prostaglandins E and F of the 1-, 2- and 3-series in a marine fish deficient in
      delta5 fatty acyl desaturase.
AB  - The effects of gamma-linolenic acid-rich borage oil (BO), in combination with
      different marine oils, namely an eicosapentaenoic acid (EPA) rich oil (MO) or a
      DHA-rich oil (TO), on tissue fatty acid composition and prostaglandin production
      were investigated in turbot, a species which lacks appreciable delta5 fatty acyl
      desaturase activity. The juvenile turbot grew well on the experimental diets and
      there were no significant differences in final weights between dietary
      treatments. Irrespective of the marine oil component, both the BO-containing
      diets increased tissue phospholipid levels of 18:2n-6 and 18:3n-6, and their
      respective elongation products, 20:2n-6 and 20:3n-6, compared to fish fed a
      control diet containing a standard Northern hemisphere fish oil. Both the BO
      containing diets increased the production of 1-series prostaglandins (PG), this
      being observed across all tissues investigated with PGF and especially PGE. The
      BO/MO diet also reduced 20:4n-6 in tissue phospholipids without affecting 20:5n
      3, whereas the BO/TO combination decreased 20:5n-3 but increased 20:4n-6. The
      production of 2-series and 3-series PGs was also altered by the dietary
      treatments but the changes were less dependent upon the tissue levels of their
      respective precursor fatty acids, 20:4n-6 and 20:5n-3. The BO-containing diets
      had very significant effects on gross fatty acid compositions of the
      phospholipids including increased proportions of saturated fatty acids and n-6
      polyunsaturated fatty acids (PUFA) and decreased proportions of monounsaturated
      fatty acids and n-3 PUFA. Overall, this study shows that eicosanoid production in
      turbot tissues can be influenced by dietary fatty acids, not only by changes in
      the absolute and relative levels of specific eicosanoid precursor PUFA in tissue
      phospholipids, but also by general effects on membrane composition, structure and
      function induced by gross fatty acid compositional changes.

PMID- 9250696
TI  - Protein kinase C mediates angiotensin II-induced contractions and the release of
      endothelin and prostacyclin in rat aortic rings.
AB  - Angiotensin II (Ang II) stimulation of vascular smooth muscle results in a myriad
      of intracellular signals that interact to produce the final physiologic response
      of the cell. We used rat aortic rings to investigate the role of protein kinase C
      (PKC) in Ang II-induced contractions and in the concomitant release of endothelin
      (ET) and prostacyclin (PGI2). Ang II (10(-9) M) produced a rapid contraction
      which was sustained for 10 min. When aortic rings were pretreated with graded
      concentrations of each of the four different inhibitors of PKC, that is, (i) 1-(5
      isoquinolinesulfonylmethyl) piperazine (H7); (ii) 1-(5-isoquinolinesulfonyl)
      piperazine(CL); (iii) staurosporine; or (iv) calphostin C, inhibition of Ang II
      induced contractions began at 10(-9) M, and was nearly complete at 10(-6) M. Ang
      II-induced contractions were associated with a 10-fold increase in the release of
      both ET and PGI2. Pretreatment with 10(-6) M of any one of the same four PKC
      inhibitors blocked Ang II-induced release of both ET and PGI2. Pretreatment with
      a blocker of the endothelin-A receptor, BQ123 (10(-6) M), inhibited, by
      approximately 50%, Ang II-induced contractions, and the release of both ET and
      PGI2. In aortic rings denuded of endothelium, Ang II-induced contractions, and
      the release of both ET and PGI2 were significantly reduced, compared to intact
      rings. We conclude that PKC mediates Ang II-induced contractions in rat aortic
      rings and that the secondary release of both ET and PGI2 during Ang II-induced
      contractions is mediated, at least in part, by PKC. In addition, approximately
      half of Ang II-induced contractile force and of PGI2 release is dependent upon
      the ET released from endothelial cells.

PMID- 9250697
TI  - Age-related changes in essential fatty acid metabolism in cultured rat heart
      myocytes.
AB  - We previously demonstrated that cultured neonatal rat myocytes have the capacity
      to desaturate/elongate essential fatty acids, alpha-linolenic acid conversion
      being higher than linoleic acid conversion. The whole process of highly
      unsaturated fatty acid formation from linoleic and alpha-linolenic acids slows
      with aging. In this study we grew heart myocytes in culture for different periods
      of time, and we observed a decrease in the desaturating/elongating activities for
      both substrates as the cells aged in culture. Alpha-linolenic acid conversion
      into highly unsaturated fatty acids was less impaired by aging than linoleic acid
      conversion. These modifications are correlated to the age-dependent alterations
      observed in the total lipid fatty acid composition, which caused a decrease in
      the unsaturation index. Changes in the lipid composition that occur in aging
      cultures parallel those reported for several tissues upon aging in the whole
      animal. The data herein reported may suggest the possibility of counteracting the
      effects of aging on lipid metabolism by supplementing cultures with appropriate
      amounts of highly unsaturated fatty acids.

PMID- 9250698
TI  - Level of polyunsaturated fatty acids and the n-6 to n-3 polyunsaturated fatty
      acid ratio in the rat diet alter serum lipid levels and lymphocyte functions.
AB  - In order to further examine the effects of dietary polyunsaturated fatty acids
      (PUFA) upon blood lipid levels and lymphocyte functions, weanling rats were fed
      for 6 weeks on high fat (178 g/kg) diets which differed in the ratio of n-6:n-3
      PUFA (100, 20, 10, 5, 1) and in the absolute level of PUFA (17.5 or 35 g/100 g
      fatty acids). The n-6:n-3 PUFA ratio of the diets was decreased by replacing
      linoleic acid with alpha-linolenic acid while the PUFA content of the diets was
      decreased by replacing PUFA with palmitic acid. Serum cholesterol concentrations
      decreased as the n-6:n-3 PUFA ratio of the low PUFA diet decreased. The ex vivo
      proliferation of spleen lymphocytes from rats fed the low PUFA diets decreased as
      the n-6:n-3 PUFA ratio of the diet decreased; the proliferation of spleen
      lymphocytes from high PUFA-fed rats was less affected by the n-6:n-3 PUFA ratio
      of the diet. Natural killer cell activity was lower for spleen lymphocytes from
      rats fed high PUFA diets with n-6:n-3 PUFA ratios of 100 or 20 than for those
      from rats fed low PUFA diets with these ratios. The natural killer cell activity
      of spleen lymphocytes decreased as the n-6:n-3 PUFA ratio of the low PUFA diet
      decreased. These findings indicate that dietary alpha-linolenic acid has
      significant blood lipid-lowering and immunomodulatory effects in rats, but that
      the effect is dependent upon the total PUFA content of the diet. The ratios of
      linoleic and alpha-linolenic acids to other fatty acids (e.g. palmitic, oleic)
      are important in determining the precise effect of manipulations of the fatty
      acid composition of the diet.

PMID- 9250699
TI  - Glutamine transport in human and rat placenta.
AB  - Glutamine plays an important role in fetal nutrition. This study explored the
      transport of [3H]glutamine into apical and basal predominant membrane vesicles
      derived from rat and human placenta. Na+-dependent glutamine transport was
      present in both apical and basal predominant vesicles derived from 20- and, to a
      lesser degree, 14-day gestation rat placenta. Amino-acid transport systems A, ASC
      like, B(o,+) (in apical membrane vesicles) and, perhaps, y+L were involved in Na+
      dependent glutamine transport. Na+-dependent glutamine uptake into human
      placental microvillus and basolateral membrane vesicles also occurred via several
      distinct transport activities. Glutamine transport via system N was not detected
      in either rat or human placental preparations. Na+-dependent glutamine transport
      in the rat was more pronounced in basal as compared to apical membrane vesicles.
      Conversely, in the human preparations, activity was significantly higher in
      microvillus as compared to basolateral membrane vesicles. It is concluded that
      Na+-dependent glutamine transport occurs through a variety of transport agencies
      in both the rat and human placenta. Transport varies with ontogeny and between
      species.

PMID- 9250700
TI  - Effect of ethanol on human placental transport and metabolism of adenosine.
AB  - It has been suggested that adenosine is involved in the acute effects of ethanol
      in a number of tissues. The present study was undertaken to evaluate the role of
      adenosine on the vascular responses of perfused isolated human placental
      cotyledons after the acute administration of ethanol. The possibility that
      ethanol may effect the uptake and metabolism adenosine was also investigated.
      Uptake of adenosine was studied using the single-circulation paired-tracer
      dilution technique. Both adenosine and ethanol caused a dose-related increase in
      perfusion pressure of placental lobules. Pharmacologically relevant
      concentrations of ethanol (10-65 mM) significantly inhibited the uptake of
      [3H]adenosine between 25 and 50 per cent. Thin-layer chromatographic analysis of
      the perfusate after the administration of ethanol showed in a 17.9 +/- 0.6 per
      cent reduction of [3H]adenosine metabolism. These findings support the working
      hypothesis that placental adenosine, at least partially, mediates the placental
      disturbance elicited by the administration of acute ethanol, which may contribute
      to the pathogenesis of fetal alcohol syndrome.

PMID- 9250701
TI  - Ovine glucose transporter-1 and -3: cDNA partial sequences and developmental gene
      expression in the placenta.
AB  - Transplacental glucose transfer utilizes specific glucose transporter (GLUT)
      proteins. cDNAs encoding ovine placental GLUT1 and GLUT3 genes were isolated,
      cloned and sequenced and then used to investigate their developmental regulation
      in ovine placenta. A cDNA of approximately 2.2 kb was isolated from a Clontech
      lambda gt10 ovine adult liver cDNA library using a 436-bp rat GLUT1 cDNA probe.
      Sequence data obtained from this clone (1600 bp) demonstrated 97 per cent
      homology to nucleotides 477-2079 of bovine GLUT1. The deduced amino acid sequence
      of the ovine cDNA presented 99 per cent identity to amino acid 103-493 of bovine
      GLUT1, and 97-98 per cent identity to corresponding regions in human and rat
      GLUT1 deduced amino acid sequences. Reverse transcription-PCR (RT-PCR) was used
      to isolate an ovine cDNA fragment from placental total RNA. Forward and reverse
      primers (16 mer) were designed to amplify a predicted 483-bp fragment between the
      second transmembrane-spanning domain (M2) and intracellular loop of GLUT3. The
      deduced 161 amino acid sequence of the ovine cDNA demonstrated 84 and 88 per cent
      identity with murine and human GLUT3. These cDNAs were used to investigate the
      ontogeny of placental oGLUT1 and oGLUT3 gene expression by Northern analysis.
      Total RNA was extracted from ovine placenta at gestational days 45, 60, 90, 120
      and 138 (n=6 per time point). Ovine GLUT1 gene expression increased significantly
      from days 45 to 60 (P<0.05), peaked at around day 120 of gestation, then
      decreased to about two-thirds of maximal levels by day 138 of gestation (term 147
      +/- 2). Ovine GLUT3 gene expression increased throughout gestation with
      significant increases from days 45 to 60, 60 to 120 and 120 to 138 (P<0.05). This
      study confirms the presence of both GLUT1 and GLUT3 genes in the ovine placenta
      and demonstrates ontogenic regulation of gene expression. The difference in
      temporal gene expression between oGLUT1 and oGLUT3 suggests distinct roles for
      each transporter during development. The nucleotide sequences reported in this
      paper have been submitted to the GenBank/EMBL Data Bank under accession numbers
      U89029 (oGLUT1) and U89030 (oGLUT3).

PMID- 9250702
TI  - Synthesis of beta2 glycoprotein 1 by the human placenta.
AB  - Autoantibodies to negatively charged phospholipids (aPL) can cause fetal loss,
      including recurrent miscarriage and stillbirth. The immunopathogenic mechanism by
      which this occurs is unknown, but these antibodies are known to bind phospholipid
      via a protein cofactor, beta2 glycoprotein 1. This protein is localized on
      placental syncytiotrophoblast and enables the binding of aPL from maternal blood.
      In this study, reverse transcription and the polymerase chain reaction (RT-PCR)
      was used on mRNA isolated from normal human placental villous tissue and from
      human choriocarcinoma cell lines (Jeg-3, BeWo and JAr) to demonstrate that
      placental cells themselves synthesize beta2 glycoprotein 1 transcripts. Protein
      production was confirmed by immunoblotting experiments. Previous
      immunohistochemical studies were extended to demonstrate that beta2 GP1 is
      localized to extravillous cytotrophoblast in addition to syncytiotrophoblast.
      Production of beta2 glycoprotein 1 by fetal trophoblast indicates this protein is
      likely to have a physiological function in the placenta, and hence aPL may induce
      their pathological effect in pregnancy by inhibiting the function of placental
      beta2 glycoprotein 1.

PMID- 9250703
TI  - Stimulation of phosphatidylcholine turnover by beta-phorbol ester and
      diacylglycerol in the primordial human placenta: the suggested role of
      phospholipase D activation.
AB  - The effects of 4beta-phorbol-12-myristate-13-acetate (PMA) and 1,2-(sn)
      dioctanoylglycerol (DOCG) on the phosphatidylcholine (PC) turnover (defined as
      degradation to diacylglycerol followed by PC resynthesis) and on the activity of
      PC-specific phospholipase D were investigated in placental mince incubated with
      various radiolabelled precursors in vitro. Experiments with [32P]phosphate
      indicated that 1 microM PMA and 125-250 microM DOCG were the lowest
      concentrations that led to maximal and selective stimulation of PC labelling.
      Moreover, PMA and DOCG acted along different time courses: PMA enhanced labelling
      after 60 min incubation, with a lag period of at least 30 min, whereas DOCG
      stimulated PC labelling after only 30 min with no further increase in the next 30
      min. The following findings suggest that increased labelling of PC with
      [32P]phosphate in PMA-treated tissue reflects an increased rate of PC turnover:
      (1) the effects of PMA and DOCG were additive and PMA did not have any effect on
      the labelling of PC(DOCG) indicating that it stimulated PC labelling even if it
      did not activate CTP:choline cytidylyl transferase, the regulatory enzyme of PC
      synthesis de novo; (2) PMA did not increase the labelling of PC from [3H]glycerol
      or [3H]glucose ruling out a PMA-promoted availability of glycolytic and/or
      lipolytic intermediates for PC formation; and (3) the PMA effect was attended by
      an increased labelling of phosphatidic acid whereas there was no change in the
      labelling of lyso-PC, indicating the activation of phospholipase D. Experiments
      in which the transphosphatidylation reaction between [3H]myristic acid-labelled
      PC and ethanol was used to estimate phospholipase D activity showed 2.4-fold and
      1.4-1.8-fold activations by PMA and DOCG, respectively, with no additivity noted.
      These results suggest that PMA stimulates PC turnover in the early human placenta
      via the activation of phospholipase D. Rapid metabolic conversion decreases the
      capacity of DOCG to accelerate PC-turnover and to activate phospholipase D. The
      early DOCG-induced stimulation of PC labelling with [32P]phosphate is attributed
      mainly to its known activating effect on CTP: choline cytidylyl transferase.

PMID- 9250704
TI  - Aminophospholipid translocase activity in JEG-3; a choriocarcinoma model of
      cytotrophoblast differentiation.
AB  - The plasma membrane is characterized by a non-symmetrical distribution of
      phospholipids; the outer monolayer of the plasma membrane consists primarily of
      phosphatidylcholine (PC), and the aminophospholipids, phosphatidylserine (PS) and
      phosphatidylethanolamine (PE), preferentially reside in the inner monolayer.
      Asymmetry is maintained by a membrane associated ATP-dependent aminophospholipid
      translocase that preferentially relocates PS and PE from the outer to the inner
      monolayer. Although in most cells the translocase minimizes expression of PS on
      the outer surface, differentiating trophoblasts express increasing levels of
      surface PS. One possible explanation of prolonged PS externalization is that
      trophoblasts lack an effective aminophospholipid translocase. To test this
      hypothesis, fluorescent PC and PS analogues, NBD-PC and NBD-PS, were introduced
      into the plasma membrane of a choriocarcinoma model of trophoblast, JEG-3 cells.
      After incubation, the fluorescent lipid remaining on the outer monolayer was
      removed by incubation with fetal bovine serum. JEG-3 cells selectively
      translocated 80 per cent of the NBD-PS without significant translocation of NBD
      PC. The process was significantly inhibited by N-ethylmaleimide (NEM) and
      vanadate. It is concluded that this model of trophoblast contains an active
      aminophospholipid translocase.

PMID- 9250705
TI  - Expression of Ras GTPase-activating protein (GAP) in human normal chorionic villi
      and hydatidiform mole.
AB  - Ras GTPase-activating protein (GAP), an important downregulator of Ras activity,
      has previously been shown to be abundant in human placenta. The expression of
      p120 and p100 isoforms of GAP in human normal chorionic villi (n=5) and
      hydatidiform mole (n=5) was investigated to clarify the involvement of Ras GAP in
      the growth of chorionic villi in the first trimester of pregnancy. Immunoblot
      analysis revealed that both p120- and p100-GAP isoforms were remarkably less
      expressed in mole villi than in normal chorionic villi. The expression of p100
      GAP significantly reduced in comparison with that of pl20-GAP in mole villi.
      Northern blot analysis showed that the amount of GAP mRNA reduced in hydatidiform
      mole less than one-third of that in normal chorionic villi. The GAP activity,
      measured by the effect of tissue extract on the hydrolysis of Ras-bound GTP, was
      significantly lower in hydatidiform mole than in normal chorionic villi. These
      results suggest that Ras GAP may play an important role in the normal growth and
      differentiation of human chorionic villi in the first trimester.

PMID- 9250706
TI  - Changes in the distribution pattern of galectin-1 and galectin-3 in human
      placenta correlates with the differentiation pathways of trophoblasts.
AB  - Human placentation is a complex biological phenomenon that results from precisely
      regulated interactions between cells and the extracellular matrix. Galectin- 1
      and galectin-3 belong to a newly defined family of galactose-binding lectins that
      can bind several glycoconjugates such as the basement membrane glycoprotein
      laminin, and are involved in many biological events including cell adhesion. In
      this study, the expression of these two galectins in first and third trimester
      normal human placenta was examined using single and double immunohistochemical
      staining and specific antibodies for galectins and cytokeratins. Galectin-3 was
      detected in all trophoblastic lineages including villous cytotrophoblasts and
      extravillous trophoblasts (trophoblastic cell columns, infiltrating trophoblasts,
      endovascular trophoblasts and placental bed giant cells). On the contrary,
      galectin-1 distribution was restricted to endometrium. A reduction of galectin-3
      expression was observed from the villous trophoblasts to the trophoblastic cell
      columns. This pattern correlated with the switch from a proliferative to a
      migratory phenotype. Galectin-1 and galectin-3 were both detected in maternal
      decidual cells. Our data demonstrate a specific pattern of galectin-1 and
      galectin-3 expression in trophoblastic tissue, and suggest these lectins could
      contribute to cell-cell and cell matrix interactions of trophoblast during
      placentation.

PMID- 9250707
TI  - Constitutive and induced cytokine production by human placenta and amniotic
      membrane at term.
AB  - Results of our previous study on the immunity of human placenta and amniotic
      membranes revealed that in majority of cases these organs present constitutive
      non-specific antiviral immunity in the organ culture (OC) system. It is possible
      that interferons (IFNs), tumour necrosis factors (TNFs) and interleukin 6 (IL-6)
      may be responsible for the antiviral effect. Here, the constitutive and
      lipopolysaccharide (LPS)-induced production of these cytokines and, additionally,
      interleukin 10 (IL-10) were determined in OC of chorionic villi, decidua and
      amniotic membranes. Significant amounts of constitutive TNF-alpha (2-64 U/ml), IL
      6 (200-12,000 U/ml) and IL-10 (1-70 ng/ml) were detected in the maternal decidua
      and chorionic villi of placenta. Amniotic membranes produced lower concentrations
      of the cytokines. LPS increased the production of cytokines from two- to
      eightfold. In contrast, activity of IFN released spontaneously was found only in
      four of 50 placentae and amniotic membranes. LPS and Newcastle disease virus
      (NDV) induced IFN production in the OC system. However, the increase of IFN after
      induction was also very small (up to 32 U/ml). Individual differentiation in the
      cytokines production was observed among placentas and amniotic membranes. TNF was
      identified as type alpha with addition TNF-beta, IFN as type alpha, beta and
      gamma.

PMID- 9250708
TI  - Stereological study of the effect of altitude on the trophoblast cell populations
      of human term placental villi.
AB  - Paraffin-embedded histological material was examined from 10 placentae from
      uncomplicated pregnancies at high altitude (3000 m). This was compared with
      material from 10 placentae delivered at low altitude (500 m). The sample groups
      were matched for maternal age, gestational age and parity. Within terminal and
      intermediate villi the volume-weighted mean cytotrophoblast cell volume did not
      significantly change at high altitude (754.1 microm3 at low altitude versus 796
      microm3 at high altitude). The fractional volume of the villi occupied by
      cytotrophoblastic cells and their nuclei number per 10000 microm3 of villous
      tissue were significantly greater in placenta from high altitude (3.17 and 1.86
      per cent, respectively) than those from low altitude (1.05 and 0.79 per cent,
      respectively) (P<0.0004 and P<0.0058, respectively). No significant differences
      in either fractional volume of the syncytiotrophoblast or its nuclei number per
      10000 microm3 of villous tissue were observed between placentae from high (26.01
      and 11.6 per cent, respectively) and low altitude (26.33 and 11.89 per cent,
      respectively). These results suggest an increase in the number of
      cytotrophoblastic cells at high altitudes without any changes in their volume.
      Exposure to hypobaric hypoxia is thought to be the principal aetiological factor.

PMID- 9250709
TI  - Influence of hypoxia on vascular endothelial growth factor and chorionic
      gonadotrophin production in the trophoblast-derived cell lines: JEG, JAr and
      BeWo.
AB  - Growth of trophoblast tissue in early pregnancy is rapid and accomplished in an
      unusually hypoxic environment. Hypoxia has been reported to upregulate mRNA
      production of vascular endothelial growth factor (VEGF), and VEGF receptors have
      been found on trophoblast cells. These observations suggest that VEGF may have an
      important role in early placentation. This study examines the influence of
      hypoxia on both the production of the VEGF message and protein and on the
      production of human chorionic gonadotrophin (hCG) protein by the cell lines JEG,
      JAr and BeWo. Cells were grown under normoxic and hypoxic conditions for 72 h.
      The average oxygen tension in the culture media of the hypoxic cultures (6-7 kPa)
      was significantly less than in the normoxic cultures (19-21 kPa). RNA was
      extracted and message for VEGF(121), VEGF(165) and VEGF(189) found in all cell
      lines by reverse transcription and the polymerase chain reaction (RT-PCR). These
      messages were upregulated by hypoxia; findings confirmed by competitive PCR for
      VEGF and expression of the house keeping gene GAPDH. hCG and VEGF were measured
      by immunoassay. Hypoxia resulted in an increase in VEGF production (P<0.05) but
      had inconsistent effects on hCG production. In some experiments the absolute
      concentrations of hCG and VEGF in the culture media were noted to be
      significantly correlated (r>0.5, P<0.05). In addition to its role in
      angiogenesis, VEGF may have direct effects on trophoblast cells encouraging
      proliferation and invasion. These effects may be regulated in part through oxygen
      supply and hCG.

PMID- 9250710
TI  - Histological study of decidual spiral arteries and the presence of maternal
      erythrocytes in the intervillous space during the first trimester of normal human
      pregnancy.
AB  - During the first trimester in normal human pregnancy, endovascular trophoblast
      migrate along the decidual spiral arteries and invade their walls to produce
      physiological change. There is controversy as to whether invading trophoblast
      plug the arteries and prevent blood flow into the intervillous space. Using light
      microscopy, placental bed sections from 25 first trimester gravid hysterectomy
      specimens were examined. From each specimen, one section was divided into equal
      central and peripheral compartments. Maternal red blood cells were present in the
      intervillous space in all specimens, in both central and peripheral areas. In
      total, 232 decidual spiral arteries were found, each of those represented by
      several cross sections, 136 in the central area and 96 in the periphery. Seventy
      nine per cent had undergone physiological change (significantly more in the
      centre than in the periphery), 63 per cent contained scattered endovascular
      trophoblast, 20 per cent had plugs of trophoblast partially occluding the vessel
      and 17 per cent had plugs totally filling the vessel lumen. These data confirm
      that in the first trimester of normal pregnancy, maternal blood enters the
      intervillous space, total plugging of the arterial system by trophoblast is not
      common, and more spiral arteries undergo physiological change in the centre than
      in the periphery.

PMID- 9250711
TI  - Experimental evidence of secretion by mouse granulated metrial gland cells.
AB  - Granulated metrial gland cells are cytotoxic cells found in the uterine wall in
      pregnancy. In this study, the involvement of the cytoplasmic granules of mouse
      granulated metrial gland cells during cytolysis of fibrosarcoma Wehi 164 cells
      was investigated in vitro. Using the lectin Helix pomatia agglutinin which binds
      to the granule membrane, but not to the cell membrane, of mouse granulated
      metrial gland cells, the limiting membrane of one or more cytoplasmic granules
      became incorporated into the cell membrane of the granulated metrial gland cells
      during cytolysis of Wehi 164 cells. It is concluded that this occurs during
      exocytosis of the contents of the granules and describes the first experimental
      evidence of secretion by mouse granulated metrial gland cells.

PMID- 9250712
TI  - A direct method for investigating the transfer of endogenous nitrogen from
      maternal body protein to fetal protein.
AB  - Maternal body protein was labelled with [15N]glycine during the last third of
      pregnancy in the rat; the label was found in fetal protein, demonstrating that
      amino acids derived from maternal protein had crossed the placental membrane. The
      enrichment of fetal carcass protein was greater than that of maternal skeletal
      muscle, expressed as atoms per cent excess but similar to that of her liver.
      Enrichment of both fetal body and maternal liver declined during the period
      studied, while that of maternal skeletal muscle remained constant. The capture of
      label by fetal protein increased gradually at a rate which was the same as its
      rate of decline in the maternal liver, suggesting that the latter was a major
      source of the fetal label. The average [15N] content of the maternal liver was
      2.3 per cent of that injected, while the total conceptus content was more than
      twice this value, 5.6 per cent, indicating that more than half was contributed
      from other maternal sources as well as her liver. The results were not influenced
      by maternal food restriction of two-thirds.

PMID- 9250713
TI  - Classification and lytic activity of rodent granulated metrial gland cells.

PMID- 9250714
TI  - Endothelins and cardiac hypertrophy.
AB  - Cardiac hypertrophy is a commonly observed complication of a variety of
      cardiovascular diseases. As well as mechanical stresses such as pressure
      overload, several humoral factors may contribute to the development of cardiac
      hypertrophy. In the early 1990s, endothelin-1 (ET-1) was found to induce
      cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes. Furthermore,
      evidence is accumulating to date to support the postulate that ET-1 may function
      as an autocrine/paracrine factor in the development of cardiac hypertrophy in
      vivo as well as in vitro In this review article, I discuss physiological and
      pathophysiological roles of ET-1 and its related peptides in cardiac hypertrophy
      associated with various cardiovascular diseases.

PMID- 9250715
TI  - The stimulatory effect of opioids on cyclic AMP production in SK-N-SH cells is
      mediated by calcium ions.
AB  - The present study examines the stimulatory effect of opioids on adenosine 3':5'
      cyclic monophosphate (cyclic AMP) production in the human neuroblastoma cell line
      SK-N-SH, and its dependence on calcium. We show that, in this culture, the mu
      opioid selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin stimulates
      cyclic AMP production by 30% in a naloxone-reversible manner. This stimulation is
      completely dependent on calcium and involves the activation of calcium/calmodulin
      since it is abolished in the presence of EGTA, calcium channel blockers or N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7). The results
      suggest that the activation of calcium/calmodulin dependent adenylyl cyclases by
      opioids in SK-N-SH cells is secondary to the induction of calcium influx and the
      consequent elevation of intracellular calcium level.

PMID- 9250716
TI  - Latrunculin A is a potent inducer of aggregation of polymorphonuclear leukocytes.
AB  - We have shown that latrunculin A, a toxin from a Red Sea sponge which has
      striking effects in several phenomena dependent on the cytoskeleton, is a potent
      inducer of aggregation of rabbit polymorphonuclear leukocytes in a dose- and time
      dependent manner. From 12 nM to 60 nM toxin the degree of aggregation (after 8
      min) in nearly directly proportional to the toxin concentration; the aggregation
      effect is energy-dependent from the glycolytic pathway. It was also shown that
      120 nM latrunculin A, after 5 min incubation, can reduce to more than half the F
      actin percent of the leucocytes. These results may contribute to the study of the
      relations between the actin cytoskeleton of leukocytes and the process of
      aggregation which is involved in important physiological functions of these
      cells.

PMID- 9250717
TI  - Effects of fructose-1,6-biphosphate on microsphere-induced cerebral ischemia in
      the rat.
AB  - Fructose-1,6-bisphosphate has been shown to exert beneficial effects in different
      experimental models of cerebral ischemia. In view of this evidence, we have
      determined whether the compound protects the brain during microsphere-induced
      ischemia. One thousand two hundred microspheres were injected into female rats
      through a catheter inserted into the right common carotid artery and, 15 minutes
      and again 24 hours later, we intravenously treated the animals with 333 mg Kg(-1)
      of fructose-1,6-bisphosphate. The injection of microspheres produced significant
      changes in the rats' gross behavior, in their performance in the beam walking
      test, and in their brain lactate concentrations. The treatment with fructose-1,6
      bisphosphate significantly attenuated the behavioral alterations induced by
      microsphere ischemia, but not in reducing brain accumulation of lactate.
      Moreover, the compound was shown to ameliorate the blood-brain barrier
      dysfunction, produced 2 and 4 hours after microsphere injection, evaluated by the
      Evans blue method. These results suggest that fructose-1,6-bisphosphate possesses
      salutary properties against the damages induced by microsphere ischemia.

PMID- 9250718
TI  - Presence of a human-like thyroid stimulating hormone (TSH) in Ciona intestinalis.
AB  - Using a monoclonal antibody against human Thyroid Stimulating Hormone (TSH), we
      have found that the invertebrate Ciona intestinalis (phylum Chordata, subphylum
      Tunicata) contains a previously unreported protein which is immunoreactive for
      anti-human TSH. The amount of this hormone in the blood, endostyle and ovary of
      C. intestinalis was found to be 0.01+/-0.003, 1.05+/-0.2 and 3.61+/-1.25
      microIU/g of tissue, respectively, using the RIA method, and a value of 0.013+/
      0.0043, 1.16+/-0.30 and 3.85+/-1.32 microIU/g using an immuno-chemiluminescent
      method. In addition to possessing immunological properties, this protein is able
      to induce the synthesis of cAMP in rat thyroid cell culture (FRTL-5) and in
      Chinese Hamster Ovary cells (CHO) transfected with the cDNA for human TSH
      receptor. This indicates that the putative ciona TSH has the capability to react
      specifically with receptors for mammalian TSH. Maximum concentrations of ciona
      TSH-like factor occur during periods of sexual maturity (between May to July),
      whereas very low concentrations were assayed during the rest of the year
      suggesting that this hormone may be involved in hormonal function related to
      sexual maturity. From a phylogenetic point of view, the above data supports the
      hypothesis for a common origin of a thyroid hormonal system between Tunicata and
      vertebrates.

PMID- 9250719
TI  - PACAP hybrid: a new PACAP receptor antagonist.
AB  - The effects of pituitary adenylate cyclase activating polypeptide (PACAP) hybrid,
      a synthetic antagonist, was investigated on NIH/3T3 cells containing PACAP
      receptor (R) splice variants (SVs). PACAPhybrid inhibited 125I-PACAP-27 binding
      to NIH/3T3 cells stably expressing PACAP-R basic, SV-1, SV-2 or SV-3 with an IC50
      of 1000 nM. PACAPhybrid antagonized the ability of PACAP-27 to elevate cAMP
      regardless of the PACAP-R SV used. PACAP was more efficacious at increasing
      cytosolic Ca2+ in NIH/3T3 cells containing PACAP-R SV-2 than PACAP-R basic, SV-1
      or SV-3. PACAPhybrid antagonized the increase in cytosolic Ca2+ caused by PACAP
      27 regardless of the PACAP-R SV used. PACAP was more potent at elevating c-fos
      mRNA using NIH/3T3 cells transfected with PACAP-R SV-2 than PACAP-R basic, SV-1
      or SV-3. PACAPhybrid antagonized the increase in c-fos mRNA caused by PACAP-27.
      These data suggest that PACAPhybrid is a useful PACAP receptor antagonist for
      PACAP-R SVs.

PMID- 9250720
TI  - Effect of 5-bromo-2'-deoxyuridine on the proliferative activity of thymus and
      regenerating adrenal cortex.
AB  - 5-Bromo-2'-deoxyuridine (BrdU) has been recently found to enhance adrenal
      glucocorticoid secretion in rats. Since BrdU-labeling is today the most employed
      technique for assessing cell proliferation, we have investigated whether this
      side-effect of BrdU may influence mitotic activity (as evaluated by metaphase
      arrested cell counting) in the thymus cortex and regenerating adrenal cortex.
      BrdU (1 mg/100 g body weight) evoked a 6-fold rise in the blood level of
      corticosterone in intact rats, but not in animals bearing regenerating adrenals,
      in which glucocorticoid secretion was very low. Mitotic index in the thymus of
      intact rats was not changed by BrdU, but it was strongly depressed in
      regenerating adrenals. These findings rule out the possibility that the
      glucocorticoid secretagogue action of BrdU exerts a sizable effect on the
      proliferative activity of both thymus and adrenal cortex. The marked lowering in
      the mitotic rate in the regenerating adrenal cortices could be ascribed to the
      well-know differentiation promoting action of BrdU, a finding which, if
      confirmed, would make highly unreliable the use of BrdU-labeling technique in
      cultures of adrenocortical cells.

PMID- 9250721
TI  - Increased cartilage and bone formation in spontaneously hypercholesterolemic
      rats.
AB  - Spontaneously hypercholesterolemic (SHC) rats are known to exhibit accelerated
      bone resorption. We compared endochondral bone formation induced by implantation
      of demineralized bone matrix (DBM) to 4-week-old SHC rats with that of age
      matched Sprague-Dawley (SD) rats. When DBM prepared from adult SD rats was
      implanted, the cartilageous area enlarged, and C-propeptide of type II
      procollagen content on day 7 was higher in SHC rats. Alkaline phosphatase
      activity and calcium content on day 12 and tartrate-resistant acid phosphatase
      activity on day 19 were higher in SHC rats. These results suggest active
      chondrogenesis, with a subsequent increase in osteogenesis, and stimulated
      osteoclastic bone resorption in SHC rats. When DBM from 10-week-old SHC rats was
      implanted into SD or SHC rats, the levels of bone forming parameters on day 12
      were reduced to one-third, suggesting inhibiting factor(s) for bone induction in
      bone matrix of SHC rats. In contrast, when DBM from 6-month-old SHC rats was
      implanted, although bone forming parameters in SD rats were comparable to the
      case of implantation of DBM from SD rats, the accelerated bone formation detected
      in SHC rats was blocked, indicating resistance to systemic bone inducing
      factor(s) of SHC rats in aged bone matrix. These results suggest that age-related
      decrease in responses to some systemic bone inducing factor may lead to the bone
      loss with advancing age.

PMID- 9250722
TI  - Suppressed bone induction by follistatin in spontaneously hypercholesterolemic
      rat bone.
AB  - Bone inducing activity in demineralized bone matrix (DBM) of young spontaneously
      hypercholesterolemic (SHC) rats has been shown to be lower than that of aged SHC
      rats. This study examined the involvement of bone follistatin, an activin-binding
      protein, in bone induction. Immunoreactive follistatin was higher in DBM from 10
      week-old SHC rats (DBM-10wk) than in DBM from 6-month-old SHC rats (DBM-6mo).
      When DBM without follistatin supplement was implanted, the C-propeptide of type
      II procollagen and calcium contents on day 12 in implants of DBM-6mo were 68% and
      40% higher than those of DBM-10wk, respectively. In contrast, follistatin
      supplement to DBM decreased C-propeptide of type II procollagen and calcium
      contents in implants of both DBM-10wk and DBM-6mo, and the levels of these
      parameters were comparable between DBM-10wk and DBM-6mo, indicating reduced
      formation of cartilage and bone. These findings suggest that 1) follistatin
      content in bone matrix decreases with advancing age in SHC rats, and 2) the
      follistatin interferes with endochondral bone formation. We demonstrate that the
      lower bone induction of DBM from young SHC rats was partly due to the abundance
      of follistatin in bone matrix.

PMID- 9250723
TI  - Prednisolone and azathioprine worsen the cyclosporine A-induced oxidative
      phosphorylation decrease of kidney mitochondria.
AB  - We investigated the effects of cyclosporine A, prednisolone and azathioprine on
      respiration rates, Ca2+-induced swelling and Ca2+ fluxes of rat kidney
      mitochondria. The three drugs significantly decreased the succinate induced
      respiration rates according to concentration-dependent processes. Each drug
      inhibited about 10% of the respiratory control ratio, with EC50 of 3.7 x 10(-7)
      M, 5.8 x 10(-9) M for cyclosporine A and azathioprine respectively. Prednisolone
      was the most effective (19.2%) acting by a two-step process with EC50 of 9.2 x
      10(-12) M and 1.9 x 10(-8) M. The combination of the three drugs developed a
      higher significant decrease of respiratory control ratio than that of each drug
      but lower than the sum of their respective effects. Inhibitions of swelling and
      Ca2+ fluxes through mitochondrial membrane due to the combination were not
      different from those induced by cyclosporine A alone. The action mechanisms of
      cyclosporine A and prednisolone were total and partial Ca2+ dependent
      respectively. Azathioprine appears to act by a Ca2+-independent one. It is
      concluded that azathioprine and prednisolone may worsen cyclosporine A-induced
      renal mitochondrial alteration of oxidative phosphorylation.

PMID- 9250724
TI  - Curcumin protects bleomycin-induced lung injury in rats.
AB  - The present study was designed to determine the protective effects of curcumin
      against bleomycin (BLM)-induced inflammatory and oxidant lung injury. The data
      indicate that BLM-mediated lung injury resulted in increases in lung lavage fluid
      biomarkers such as total protein, angiotensin-converting enzyme (ACE), lactate
      dehydrogenase (LDH), N-acetyl-beta-D-glucosaminidase (NAG), lipid peroxidation
      (LPO) products, superoxide dismutase (SOD) and catalase. Bleomycin administration
      also resulted in increased levels of malondialdehyde (MDA) in bronchoalveolar
      lavage fluid (BALF) and bronchoalveolar lavage (BAL) cells and greater amounts of
      alveolar macrophage (AM) superoxide dismutase activity. By contrast, lower levels
      of reduced glutathione (GSH) were observed in lung lavage fluid, BAL cells and
      AM. Stimulated superoxide anion and hydrogen peroxide release by AM from BLM rats
      were found to be higher. Curcumin treatment resulted in a significant reduction
      in lavage fluid biomarkers. In addition, curcumin treatment resulted in the
      restoration of antioxidant status in BLM rats. These data suggest that curcumin
      treatment reduces the development of BLM-induced inflammatory and oxidant
      activity. Therefore, curcumin offers the potential for a novel pharmacological
      approach in the suppression of drug or chemical-induced lung injury.

PMID- 9250725
TI  - The secretory response of hypothalamic beta-endorphin neurons to acute and
      chronic nicotine treatments and following nicotine withdrawal.
AB  - In the present study, we determined the effect of acute and chronic nicotine
      treatments on the secretion of immunoreactive beta-endorphin (IR-beta-EP) and
      cell viability of cultured hypothalamic neurons. Also, we determined the
      secretory response of IR-beta-EP following withdrawal from a long-term nicotine
      treatment. Fetal hypothalamic cells were dissociated and maintained in cultures
      for 9 days and were treated with various doses of nicotine (1, 6, 12 and 18
      microM) for 6 h (acute treatment) or treated with nicotine at 12 h intervals for
      96 h (chronic treatment). Determination of IR-beta-EP concentrations in the media
      revealed that 6-18 microM doses of nicotine increased IR-beta-EP secretion from
      these cultures for a period of 24 h; after this period, the cultured cells did
      not respond to these doses of nicotine. The desensitization of beta-EP neurons 24
      h after treatment with nicotine did not appear to be related to the loss of
      viable cells. Determination of withdrawal response after 72 h of constant
      nicotine (6 microM) treatments revealed that the hypothalamic neurons secrete
      elevated amounts of IR-beta-EP for a period of 72 h after nicotine withdrawal.
      These results suggest that: 1) acute treatment with nicotine stimulates
      hypothalamic IR-beta-EP release; 2) chronic nicotine treatment desensitizes beta
      EP-secreting neurons and, 3) beta-EP neurons in primary culture show withdrawal
      response to nicotine.

PMID- 9250726
TI  - Whiplash injuries.

PMID- 9250727
TI  - Arthroscopy and MRI for the knee.

PMID- 9250728
TI  - Antibiotic prophylaxis, dental treatment and arthroplasty: time to explode a
      myth.

PMID- 9250730
TI  - Results of nerve grafting for injuries of the axillary and suprascapular nerves.
AB  - We report the results in 33 patients who had nerve grafting of the axillary or
      the suprascapular nerve or of both. There were 32 men and one woman; their mean
      age was 21 years and the average interval between injury and operation was three
      months. At a mean follow-up of 27 months, the deltoid had recovered to M3 or
      better in 23 of 30 patients (77%) and the infraspinatus in 18 of 25 patients
      (72%). Shoulder elevation had reached 120 degrees or more in 27 patients (82%),
      with external rotation of 30 degrees or more in 27 (82%). Twenty-six patients
      (79%) could reach to the top of their head with their hand. Recovery of muscle
      strength, range of movement and shoulder function were satisfactory when surgery
      was performed within four months of the injury. Early exploration and nerve
      grafting can lead to a good functional recovery, but thorough exploration and
      careful repair of both nerves are essential.

PMID- 9250729
TI  - The behavioural response to whiplash injury.
AB  - We studied 50 consecutive patients presenting at an accident department after
      rear-end vehicle collisions and recorded symptoms and psychological test scores
      within one week of injury, at three months and at two years. The range of neck
      movement was noted at three months. Within one week of injury, psychological test
      scores were normal in 82% of the group but became abnormal in 81% of the patients
      with intrusive or disabling symptoms at over three months (p < 0.001) and
      remained abnormal in 69% at two years. The clinical outcome after two years could
      be predicted at three months with 76% accuracy by neck stiffness, 74% by
      psychological score and 82% by a combination of these variables. The severity of
      symptoms after a whiplash injury is related both to the physical restriction of
      neck movement and to psychological disorder. The latter becomes established
      within three months of the injury.

PMID- 9250731
TI  - Full exposure of the axillary and suprascapular nerves.
AB  - We describe a method of exposing the whole length of the axillary and
      suprascapular nerves through a sabre-cut incision. The coracoid process is
      osteotomised and part of trapezius is detached from its insertions. The posterior
      deltoid is freed from its scapular origin to expose infraspinatus. We have used
      this approach to explore combined injuries of the axillary and suprascapular
      nerves with good results, and no serious complications. Its success depends on a
      meticulous surgical technique.

PMID- 9250732
TI  - Injury to the brachial plexus by a fragment of bone after fracture of the
      clavicle.
AB  - Clavicular fractures are occasionally responsible for lesions of the brachial
      plexus. The symptoms are usually delayed and due to compression by hypertrophic
      callus, nonunion or a subclavian pseudoaneurysm. We describe a patient in whom a
      displaced bone fragment was pressing on the retroclavicular part of the brachial
      plexus, leading to early symptoms of a lesion of the posterior cord. Internal
      fixation of the clavicle and external neurolysis of the brachial plexus gave an
      almost full recovery.

PMID- 9250733
TI  - Closed treatment of displaced middle-third fractures of the clavicle gives poor
      results.
AB  - We evaluated 242 consecutive fractures of the clavicle in adults which had been
      treated conservatively. Of these, 66 (27%) were originally in the middle third of
      the clavicle and had been completely displaced. We reviewed 52 of these patients
      at a mean of 38 months after injury. Eight of the 52 fractures (15%) had
      developed nonunion, and 16 patients (31%) reported unsatisfactory results.
      Thirteen patients had mild to moderate residual pain and 15 had some evidence of
      brachial plexus irritation. Of the 28 who had cosmetic complaints, only 11
      considered accepting corrective surgery. No patient had significant impairment of
      range of movement or shoulder strength as a result of the injury. We found that
      initial shortening at the fracture of > or = 20 mm had a highly significant
      association with nonunion (p < 0.0001) and the chance of an unsatisfactory
      result. Final shortening of 20 mm or more was associated with an unsatisfactory
      result, but not with nonunion. No other patient variable, treatment factor, or
      fracture characteristic had a significant effect on outcome. We now recommend
      open reduction and internal fixation of severely displaced fractures of the
      middle third of the clavicle in adult patients.

PMID- 9250734
TI  - Anterior dislocation of the shoulder in elderly patients.
AB  - Of 545 consecutive patients with anterior shoulder dislocations, 108 (20%) were
      aged 60 years or more at the time of injury. We reviewed and radiographed 95 of
      these elderly patients after a mean follow-up of 7.1 years. Axillary nerve
      injuries were seen in 9.3% of the 108 patients, but all recovered completely in 3
      to 12 months. There were single or multiple recurrences of dislocation in 21
      patients (22.1%), but within this group age had no influence on the tendency to
      redislocate. Tears of the rotator-cuff were diagnosed by imaging studies or
      clinically in 58 patients (61%), including all who had redislocations. Sixteen
      patients required surgery. Eight with a single dislocation and a cuff tear had
      only repair of the torn cuff. Of the eight patients with multiple dislocations
      requiring operation, five also had a torn cuff and needed either a stabilising
      procedure and a cuff repair or repair of the cuff only. All patients who were
      operated on had a satisfactory result, with the exception of those with multiple
      redislocations and a cuff tear who had repair of the cuff only. Anterior shoulder
      dislocation in elderly subjects is more common than is generally believed; 20%
      suffer redislocation and 60% have a cuff tear. Operation may be needed to repair
      a torn cuff or to stabilise the shoulder. Patients with multiple redislocations
      will probably require both procedures.

PMID- 9250735
TI  - Mallet deformity of the finger. Five-year follow-up of conservative treatment.
AB  - We reviewed 31 patients at a mean of five years after mallet deformity of the
      finger had been treated with a thermoplastic splint. Intra-articular fractures
      were present in 35% of patients. Osteoarthritic changes had developed in 48%,
      most in association with fracture, and 29% had a swan-neck deformity. There was a
      loss of extension greater than 10 degrees in 35%; the average deficit at the
      interphalangeal joint was 8.3 degrees and the average flexion arc was 48.5
      degrees. Despite these findings, patient satisfaction was generally high, with
      little evidence of functional impairment.

PMID- 9250736
TI  - Skeletal metastases from soft-tissue sarcomas. Incidence, patterns, and
      radiological features.
AB  - We reviewed 277 patients with soft-tissue sarcoma (STS) treated between 1975 and
      1995 to study the incidence, distribution, time of appearance, and radiological
      findings of skeletal metastases. Of these, 28 (10.1%) had metastases within a
      mean period of 18.6 months after admission. The incidence of skeletal metastases
      differed among the histological subtypes of sarcoma; alveolar soft-part sarcoma,
      dedifferentiated liposarcoma, angiosarcoma, and rhabdomyosarcoma tended to show
      higher incidences. The regional bones close to the primary tumour were affected
      in 13 (46.4%) of the 28 patients, and the axial bones in 18 (64.3%).
      Radiologically, the metastatic bony lesions predominantly showed osteolytic
      changes, and there were pathological fractures in 21 of 44 lesions.

PMID- 9250737
TI  - Influence of local recurrence on the prognosis of soft-tissue sarcomas.
AB  - We have investigated the significance of local recurrence on survival in 173
      patients with localised soft-tissue sarcomas of the limbs and of the trunk. The
      overall survival rates at five and ten years were 75.2% and 68.0%, respectively.
      After definitive surgery at our hospitals, there was local recurrence in 25
      patients (14.5%). After inadequate operations elsewhere, there was a higher
      incidence of late local recurrence (28.3%), in comparison with those with primary
      tumours treated by us (9.0%), or patients referred to us immediately after
      inadequate surgery elsewhere (10.2%). Because of small numbers these differences
      in the survival rates were not statistically significantly different. Univariate
      survival analysis showed that local recurrence after definitive surgery (p =
      0.006) together with the histological grade (p = 0.0002), the size of the tumour
      (p = 0.002), its depth in relation to deep fascia (p = 0.003), and the surgical
      margin (p = 0.0001) were the significant prognostic factors. Local recurrence at
      the initial presentation did not affect survival. Multivariate analysis showed
      that local recurrence after definitive surgery also lost its apparent prognostic
      significance.

PMID- 9250738
TI  - The cost-effectiveness of limb salvage for bone tumours.
AB  - The use of endoprostheses for limb salvage in primary bone tumours is highly
      specialised. Studies have shown no significant difference in survival, function
      or quality of life between patients with limb salvage and those with amputation.
      We have derived a formula for calculating the ongoing costs of limb salvage with
      an endoprosthesis which is based on actual costs and uses historical data to show
      the likelihood of further surgery or revision. Comparative data for amputation
      are also shown. Using current prices, the cost-effectiveness of surgery with an
      endoprosthesis is clearly demonstrated.

PMID- 9250739
TI  - Tuberculous osteomyelitis.
AB  - Tuberculous osteomyelitis which does not involve a joint is uncommon and may fail
      to be diagnosed by an orthopaedic surgeon. We treated 28 lesions of tuberculous
      osteomyelitis in 25 patients between 1988 and 1995. The duration of symptoms was
      from two to 39 months, and most of our patients had been treated initially with
      non-steroidal anti-inflammatory drugs which failed to provide relief. Bone pain
      which does not promptly respond to analgesic medication is often due to infection
      or neoplasia. In the early stages, when plain radiographs are normal, MRI or CT
      may help to localise lesions. On plain radiographs, more advanced lesions may
      mimic chronic pyogenic osteomyelitis, Brodie's abscess, tumours or granulomatous
      lesions. Biopsy is mandatory to confirm the diagnosis, and antituberculous drugs
      are the mainstay of treatment. When operative findings at biopsy have the
      features of skeletal tuberculosis curettage of the affected bone may promote
      earlier healing.

PMID- 9250740
TI  - Evaluation of sinus-track cultures in chronic bone infection.
AB  - Sinus-track cultures were compared prospectively with cultures from operative
      specimens in 55 patients with chronic bone infection. There was a total of 115
      operative isolates; 102 of the sinus-track isolates were identical (88.7%),
      showing a specificity of 95.7% and a predictive value of 90.3%. A sinus-track
      specimen proved to be a reliable source for the isolation of all bacteria causing
      chronic bone infection except Staphylococcus epidermidis, provided that material
      from the depths of the sinus was aspirated by syringe from an active flowing
      sinus and inoculated immediately on culture media. Cotton-swab sinus specimens
      were unreliable for the isolation of mycobacteria, and could miss many pyogenic
      bacteria, or contain contaminants. Tuberculous bone infection should be suspected
      if there is no growth of any pyogenic bacteria or if there is growth of
      Staphyloccocus epidermidis alone on routine aerobic and anaerobic sinus cultures.
      Mycobacteria can often be identified from sinus-track culture from patients in
      whom operative culture, histopathology and clinical examination have failed to
      confirm the diagnosis of tuberculosis.

PMID- 9250741
TI  - The reliability of measurements of pelvic radiographs in infants.
AB  - We have evaluated the reliability of the measurement of radiological indicators
      in developmental dysplasia of the hip. Three observers each independently
      assessed 60 pelvic radiographs from infants aged from 3 to 36 months. Errors from
      the true value of a single measurement made by a single observer (E1), of the
      average of two measurements by a single observer (E2), and of the average of two
      single measurements by two different observers (E3) were established for the
      acetabular index of Hilgenreiner, for the assessment of superior and lateral
      femoral displacement and for indicators of pelvic alignment. The errors for the
      assessment of the acetabular index were E1 +/- 5 degrees, E2 +/- 5 degrees, and
      E3 +/- 3.5 degrees. There was a significant correlation between the presence of
      an acetabular notch on the radiograph and an increased error in measurement (p =
      0.01). Yamamuro's measurement of lateral femoral displacement was more reliable
      than the Hilgenreiner distance. The errors of indicators of pelvic alignment
      showed a correlation with the age of the infant; the quotient of pelvic rotation
      was more reliable after seven months of age (p < 0.0001). The errors of the
      measurement of the symphysis os-ischium angle tended to increase with age and
      those of the measurement of the index of pelvic tilt decreased with skeletal
      maturation (p = 0.002).

PMID- 9250742
TI  - Carpal tunnel syndrome in the mucopolysaccharidoses and mucolipidoses.
AB  - Children with a mucopolysaccharidosis or mucolipidosis suffer progressive
      disability of the hands, particularly in relation to dysfunction of the median
      nerve. This is an increasing problem because bone-marrow transplantation has
      dramatically improved survival without apparently changing the musculoskeletal
      manifestations. We have reviewed 48 children with these syndromes who required
      carpal tunnel decompression, recording symptoms, signs, radiological,
      electrophysiological and operative findings, histology and upper-limb function.
      In these children the carpal tunnel syndrome differs from that seen in adults.
      Symptoms are rare but signs such as decreased sweating, pulp atrophy, thenar
      wasting and manual clumsiness are much more common. At operation, the flexor
      retinaculum was thickened and a mass of white tenosynovium engulfed the flexor
      tendons. Most patients had some definite nerve constriction with a thickened
      epineurium. Functional improvement was seen after early decompression, with some
      benefit from simultaneous tendon release. Regular physiotherapy helped to
      maintain increased hand movement. We describe our assessment protocol, the
      physiotherapy and operative regime and the standard functional review which helps
      to maximise function in the hands and upper limbs of these children.

PMID- 9250743
TI  - Early radiological observations may predict the long-term survival of femoral hip
      prostheses.
AB  - We reviewed a consecutive series of 527 uninfected hip replacements in patients
      resident in the UK which had been implanted from 1981 to 1993. All had the same
      basic design of femoral prosthesis, but four fixation techniques had been used:
      two press-fit, one HA-coated and one cemented. Review and radiography were
      planned prospectively. For assessment the components were retrospectively placed
      into two groups: those which had failed from two years onwards by aseptic femoral
      loosening and those in which the femoral component had survived without revision
      or recommendation for revision. All available radiographs in both groups were
      measured to determine vertical migration and examined by two observers to agree
      the presence of radiolucent lines (RLLs), lytic lesions, resorption of the neck,
      proximal osteopenia and distal intramedullary and distal subperiosteal formation
      of new bone. We then related the presence or absence of these features and the
      rate of migration at two years to the outcome with regard to aseptic loosening
      and determined the predictive value of each of these variables. Migration of > or
      = 2 mm at two years, the presence of an RLL of 2 mm occupying one-third of any
      one zone, and subperiosteal formation of new bone at the tip of the stem were
      predictors of aseptic loosening after two years. There were too few lytic lesions
      to assess at two years, but at five years a lytic lesion > or = 2 mm also
      predicted failure. We discuss the use of these variables as predictors of femoral
      aseptic loosening for groups of hips and for individual hips. We conclude that if
      a group of about 50 total hip replacements, perhaps with a new design of femoral
      stem, were studied in this way at two years, a mean migration of < 0.4 mm and an
      incidence of < 10% of RLLs of 2 mm in any one zone would predict 95% survival at
      ten years. For an individual prosthesis, migration of < 2 mm and the absence of
      an RLL of < or = 2 mm at two years predict a 6% chance of revision over
      approximately ten years. If either 2 mm of migration or an RLL of 2 mm is
      present, the chances of revision rise to 27%, and if both radiological signs are
      present they are 50%. If at five years a lytic lesion has developed, whatever the
      situation at two years, there is approximately a 50% chance of failure in the
      following five years. Our findings suggest that replacements using a limited
      number of any new design of femoral prosthesis should be screened radiologically
      at two years before they are generally introduced. We also suggest that
      radiographs of individual patients at two years and perhaps at five years should
      be studied to help to decide whether or not the patient should remain under close
      review or be discharged from specialist follow-up.

PMID- 9250744
TI  - Antibiotic prophylaxis in total hip arthroplasty. Review of 10,905 primary
      cemented total hip replacements reported to the Norwegian arthroplasty register,
      1987 to 1995.
AB  - We have assessed the effect of different regimes of antibiotic prophylaxis on the
      survival of total hip implants, comparing antibiotics administered both
      systemically and in the bone cement, systemically only, in the bone cement only
      and with no antibiotics given. We studied 10,905 primary cemented total hip
      replacements, performed for osteoarthritis of the hip and reported to the
      Norwegian arthroplasty register between 1987 and 1995. Cox-estimated failure-rate
      ratios (FRR) are presented with adjustment for gender, age, the brand of cement,
      the prosthesis, the type of operating theatre and the operating time. For
      revisions performed for infection (39 operations), the lowest rate of revision
      was found among patients receiving antibiotic-containing cement plus systemic
      antibiotics (n = 5804). The revision rate for the 4586 patients receiving
      systemic antibiotics only was 4.3 times greater (95% CI 1.7 to 11.0, p = 0.001);
      in 239 with antibiotics in the bone cement only it was 6.3 times greater (CI 1.6
      to 25.0, p = 0.003); and in the 276 who did not receive antibiotics it was by
      11.5 times greater (CI 2.1 to 63.0, p = 0.002). Adjustment for the total amount
      of systemic antibiotic administered did not change the results. We also observed
      an increased revision rate for aseptic loosening (109 operations) comparing the
      systemic-only (FRR = 1.8, CI 1.1 to 2.9, p = 0.01) and the cement-only regimes
      (FRR = 2.6, CI 1.2 to 5.9, p = 0.02) with the combined dosage. Our findings show
      that systemic antibiotics combined with antibiotic-containing bone cement led to
      fewer revisions than the other methods.

PMID- 9250745
TI  - Prevention of heterotopic ossification after total hip replacement. A
      prospective, randomised study using acetylsalicylic acid, indomethacin and
      fractional or single-dose irradiation.
AB  - We have carried out a prospective, randomised study of prophylaxis for
      heterotopic ossification (HO) comparing indomethacin for 7 and 14 days,
      acetylsalicylic acid, and fractional (4 x 3 Gy) or single exposure of 5 or 7 Gy
      irradiation after operation. We initially had 723 patients (733 hip
      replacements), but after withdrawals there were 685 hips of which 18.4% developed
      HO; 14% were grade I, 2.9% grade II and 1.5% grade III of the Brooker
      classification. We compared the results between these groups with those of a
      matched control series and found that indomethacin, 2 x 50 mg for 7 and 14 days,
      and postoperative irradiation of 4 x 3 Gy or 1 x 7 Gy, significantly reduced the
      development of HO compared with the control group. Patients in the
      acetylsalicylic acid group and those with a single irradiation of 5 Gy after
      operation developed significantly more ossification than those in the
      indomethacin and other irradiation groups. We suggest the use of 2 x 50 mg of
      indomethacin with mucoprotection for seven days as prophylaxis against HO after
      total hip replacement for all patients. A single irradiation of 7 Gy is
      recommended for patients who have developed HO after previous operations or to
      whom administration of indomethacin is contraindicated.

PMID- 9250746
TI  - Early femoral loosening in one design of cemented hip replacement.
AB  - We have studied aseptic loosening of the femoral component in 76 patients with
      primary total hip replacement using the Capital prosthesis. The mean follow-up
      was 26 months (10 to 37). Twelve femoral components (16%) were definitely and
      eight (10%) were possibly loose. They were characterised by a thin cement mantle
      (p < 0.001) and excessive residual cancellous bone in the proximomedial region (p
      < 0.01). We recommend that the cement mantle around the prosthesis should be 2 to
      3 mm and that further long-term studies are needed to evaluate the wear
      properties of titanium-nitride-coated titanium femoral heads.

PMID- 9250747
TI  - Valgus-extension osteotomy for advanced osteoarthritis in dysplastic hips.
      Results at 12 to 18 years.
AB  - We treated 31 consecutive patients of mean age 43 years (22 to 59) with severe
      osteoarthritis of the hip secondary to dysplasia by valgus-extension osteotomy.
      The clinical results were analysed for factors which may have affected the
      outcome. The procedure was carried out only on one side and was combined with a
      Chiari pelvic osteotomy in four patients. The angle of valgus was between 30 and
      40 degrees with 10 to 20 degrees of extension. The mean follow-up was 15 years
      (12 to 18). Clinical evaluation using Charnley's modification of the system of
      Merle d'Aubigne and Postel showed that the mean score for pain had improved from
      2.3 before operation to 4.2 at 15 years, and function from 2.3 to 4.2. Range of
      movement had decreased from 4.2 to 3.5. Fifteen patients (48.4%) had a pain score
      of 5 or 6 and were evaluated as satisfactory. Kaplan-Meier survivorship analysis
      showed a survival rate of 51% at 15 years after operation. Two preoperative
      factors had a significant positive correlation with the radiological results,
      namely the thickness of the capital drop osteophyte and the length of the roof
      osteophyte. We suggest that this procedure is effective for advanced
      osteoarthritis in the dysplastic hip in young and active patients if these
      factors are satisfactory on the preoperative radiographs.

PMID- 9250748
TI  - Complete displacement of the femoral stem during dislocation of a THR.
AB  - We report an unusual complication of late dislocation of a total hip replacement.
      The femoral stem had completely migrated from the shaft. The insertion of a new
      long-stem prosthesis was successful.

PMID- 9250749
TI  - Rotator-cuff tear of the hip.
AB  - We describe an apparently unreported finding during hip operations: a tear at the
      insertion of gluteus medius and gluteus minimus. This defect may well be known to
      many surgeons with experience of hip replacement and hemiarthroplasty for
      fractures of the neck of the femur, but a Medline search has failed to find a
      previous description. We made a prospective study of 50 consecutive patients with
      fractures of the neck of the femur to quantify the incidence of this condition:
      11 (22%) had such a tear.

PMID- 9250750
TI  - Acute colonic pseudo-obstruction after total hip replacement.
AB  - Acute colonic pseudo-obstruction is a poorly recognised and potentially fatal
      complication of hip surgery. Between 1991 and 1994 six patients were observed who
      required laparotomy after failure of medical management. In three the indication
      was signs of peritonism, while in the other three exploration was required to
      exclude segmental ischaemia and to decompress the bowel. In all, there was no
      evidence of mechanical obstruction. Patients having total hip replacement are at
      risk of developing pseudo-obstruction due to their age, comorbidity, high doses
      of analgesics and the nature of the operation. If postoperative ileus persists
      for more than 48 hours acute colonic pseudo-obstruction should be suspected and
      confirmed by plain radiography. Prompt recognition and treatment with early
      referral to a colorectal unit are indicated. Laparotomy appears to carry less
      risk than that for patients with idiopathic pseudo-obstruction, but should be
      performed only if colonic ischaemia is suspected.

PMID- 9250751
TI  - MRI can prevent unnecessary arthroscopy.
AB  - We compared the practice of four orthopaedic consultants as regards the use of
      MRI and arthroscopy to diagnose problems of the knee. In one year 324
      arthroscopies and 66 MR scans were performed for this purpose. We found that MRI
      is a reliable and cheaper alternative to 'diagnostic arthroscopy'. We consider
      that patients with definite clinical signs merit an early 'therapeutic
      arthroscopy', but that all other knees should be investigated by MRI. This policy
      spares patients from unnecessary and expensive surgery. Arthroscopy for
      diagnostic purposes should be used only with a specific purpose. Modern MRI can
      and should replace "having a look".

PMID- 9250752
TI  - Preoperative factors influencing the range of movement after total knee
      arthroplasty for severe osteoarthritis.
AB  - We report a prospective study, using multivariate analysis, of the factors which
      influence the range of movement after total knee arthroplasty in 74 patients with
      83 arthroplasties at a mean follow-up of 23.6 months (12 to 41). All the patients
      had a diagnosis of osteoarthritis, a severely disabled knee with a Knee Society
      system score of less than 60, varus deformity, no previous surgery to the knee,
      identical prostheses implanted with a similar surgical technique, and no
      postoperative complications which may have affected the range of movement. The
      most important factors which influenced the range of movement after arthroplasty
      were the preoperative range of flexion and the body-weight of the patient. There
      was a significant improvement in flexion and reduction of flexion contracture at
      each successive review up to 12 months after operation. Patients with restricted
      movement before operation showed a satisfactory gain at final review.

PMID- 9250753
TI  - The clinical advantages of autologous transfusion. A randomized, controlled study
      after knee replacement.
AB  - We have carried out a randomised, controlled trial on 70 patients having
      unilateral total knee replacement in which transfusion was either with homologous
      bank blood or by reinfusion of unwashed blood salvaged after operation. No
      complications or adverse effects were observed from reinfusion. The need for bank
      blood was reduced by 86% in the reinfusion group but, more importantly, the
      number of infective episodes was significantly less when the use of bank blood
      was avoided. The mean length of stay in hospital was also reduced by more than
      two days.

PMID- 9250754
TI  - Venous haemodynamics in both legs after total knee replacement.
AB  - We studied the effect of total knee replacement on venous flow in 110 patients.
      Resting venous blood flow was measured using strain-gauge plethysmography before
      operation, after surgery and after discharge from hospital. There was a
      significant reduction in mean venous capacitance (p < 0.001) and mean venous
      outflow (p < 0.004) affecting only the operated leg. Both improved significantly
      after mobilisation in the early postoperative period, returning to preoperative
      levels by six days after surgery and before discharge from hospital. Our findings
      showed that venous stasis may contribute to deep-vein thrombosis only in the
      first few days after total knee replacement. This would be the most important
      period for the use of flow-enhancing prophylactic devices. Comparison with
      changes in blood flow after total hip replacement identified different patterns
      of altered haemodynamics suggesting that there are different mechanisms of venous
      stasis and thrombogenesis in hip and knee arthritis and during surgery for these
      conditions.

PMID- 9250755
TI  - Silicone suspension of external prostheses. A new era in artificial limb usage.
AB  - The use of silicone inner sockets, with or without the incorporation of shuttle
      locks, has greatly improved the function of artificial limbs. They cushion and
      protect the stump and provide a means for prosthetic suspension, allowing more
      comfortable use, especially in patients with ischaemic stumps. They also allow
      greater movement at the proximal joint.

PMID- 9250756
TI  - Tear of the plantar calcaneonavicular (spring) ligament causing flatfoot. A case
      report.
AB  - Acquired flatfoot deformity after injury is usually due to partial or complete
      tearing of the tendon of tibialis posterior, with secondary failure of the other
      structures which maintain the medial longitudinal arch. We describe a patient in
      whom the rupture of the plantar calcaneonavicular (spring) ligament resulted in a
      clinical picture similar to that of rupture of the tendon of tibialis posterior.
      Operative repair of the ligament and transfer of the tendon of flexor digitorum
      gave an excellent result at four years with the patient returning to full
      sporting activities.

PMID- 9250759
TI  - An anatomical study of a new portal for ankle arthroscopy.
AB  - We describe a medial midline portal between the tendons of extensor hallucis
      longus and tibialis anterior for arthroscopy of the ankle. We dissected 20
      cadaver specimens to compare the risk of neurovascular injury using this approach
      with that of using standard arthroscopic portals. Compared with the anterocentral
      portal, the medial midline was a mean of 11.2 mm further from the nearest branch
      of the superficial peroneal nerve and 10.3 mm further from the dorsalis pedis
      artery. This portal allows good access to the joint surface and intra-articular
      structures and has a lower risk of injury to the dorsalis pedis artery, deep
      peroneal nerve or the medial branch of the superficial peroneal nerve.

PMID- 9250757
TI  - The influence of subtalar and triple arthrodesis on the tibiotalar joint. A long
      term follow-up study.
AB  - From 1975 to 1990 we performed subtalar or triple arthrodesis on 54 patients; 48
      of them were reviewed after a mean follow-up of 10 years (6 to 15). There were 17
      subtalar fusions in 14 patients and 37 triple arthrodeses in 28 patients. We
      assessed tibiotalar ankle function using the criteria of Mazur which gives a
      points score of a maximum of 100. Radiological evidence of degenerative change
      was graded on a scale of 0 to 4. The mean Mazur score was 85 for the subtalar
      fusions and 78 for the triple arthrodeses. The radiological score showed no
      degenerative changes in 36 feet (24 triple and 12 subtalar arthrodeses) and an
      increase of one grade in 14 feet (10 triple and 4 subtalar), of two grades in
      three feet (all triple arthrodeses) and of three grades in one foot after a
      subtalar arthrodesis. We found no statistically significant difference in the
      radiological score in unilateral fusions between feet with subtalar and triple
      arthrodeses and the contralateral foot. In all four feet which showed an increase
      in degenerative changes of two or more grades, there was an abnormality of the
      tibiotalar joint before the fusion operation. Of the 14 feet which showed an
      increase of one grade, there was a similar increase on the contralateral side in
      nine. Our findings show that subtalar or triple arthrodesis has little adverse
      influence on the function of the tibiotalar joint, even after many years.

PMID- 9250758
TI  - Isolated bilateral recurrent dislocation of the calcaneocuboid joint. A case
      report.
AB  - An 18-year-old girl with moderate joint laxity presented with recurrent
      dislocation of the calcaneocuboid joint in both feet. We achieved successful
      stabilisation on both sides by reconstruction of the ligaments and capsule using
      the plantaris tendons.

PMID- 9250760
TI  - Resorption of hydroxyapatite and fluorapatite coatings in man. An experimental
      study in trabecular bone.
AB  - The clinical use of hydroxyapatite (HA) coating is controversial especially in
      regard to the long-term performance of the coating and the effects of resorption.
      In each of 15 consenting patients we inserted two implants, coated with either HA
      or fluorapatite (FA) into the iliac crest. They were harvested at a mean of 13.6
      +/- 0.6 months after surgery. Histological examination showed that bone ongrowth
      on the HA-coated implants was significantly greater (29%) than that on the FA
      coated implants. When bone was present on the coating surface the HA coating was
      significantly thicker than the FA coating. When bone marrow was present, the HA
      coating was significantly thinner than the FA coating. The reduction in coating
      thickness when covered by bone or bone marrow was 23.1 +/- 9.7 microm for HA and
      5.1 +/- 1.7 microm for FA (p < 0.01) suggesting that FA is more stable than HA
      against resorption by bone marrow. The findings suggest that in man the
      osteoconductive properties of HA coating are superior to those of FA. Resorption
      rates for both coatings were approximately 20% of the coating thickness per year.
      Bone ongrowth appears to protect against resorption whereas bone marrow seems to
      accelerate resorption. No adverse reaction was seen in the surrounding bone.

PMID- 9250761
TI  - Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee
      replacement for idiopathic osteoarthritis.
AB  - From a prospective, cross-sectional survey of 402 patients who had a total hip
      (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a
      major centre, we determined the prevalence of these replacements for idiopathic
      OA in their 1171 siblings and 376 spouses. Using spouses as controls, the
      relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative
      risk for TKR in siblings v spouses was 4.8 (95 % CI 0.64 to 36.4) whereas the
      risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to
      4.43) when siblings and spouses over 64 years of age were compared. Using a
      threshold liability model (Falconer), the heritability of end-stage OA of the hip
      was estimated at 27%. The increased risks of joint replacement for severe,
      idiopathic OA which we found in siblings suggest that genetic influences are
      important in end-stage OA of the hip and knee.

PMID- 9250762
TI  - Acrylic cement creeps but does not allow much subsidence of femoral stems.
AB  - It has been suggested that the endurance of cemented femoral reconstructions in
      total hip arthroplasty is affected by the creep of acrylic cement, but it is not
      known to what extent cement creeps under loading conditions in vivo, or how this
      affects load transfer. We have simulated the long-term creep properties of
      acrylic cement in finite-element models of femoral stem constructs and analysed
      their effects. We investigated whether subsidence rates measured in vivo could be
      explained by creep of acrylic cement, and if polished, unbonded, stems
      accommodated creep better than bonded stems. Our findings showed that polished
      prostheses subsided only about 50 microm as a result of cement creep. The long
      term prosthetic subsidence rates caused by creep of acrylic cement are therefore
      very small and do not explain the excessive migration rates which have sometimes
      been reported. Cement creep did, however, relax cement stresses and create a more
      favourable stress distribution at the interfaces. These trends were found around
      both the bonded and unbonded stems. Our results did not confirm that polished,
      unbonded, stems accommodated creep better than bonded stems in terms of cement
      and interface stress patterns.

PMID- 9250763
TI  - Functional outcome after experimental cauda equina compression.
AB  - Spinal nerve roots often sustain compression injuries. We used a Wistar rat model
      of the cauda equina syndrome to investigate such injuries. Rapid transient
      compression of the cauda equina was produced using a balloon catheter. The
      results were assessed by daily neurological examination and somatosensory evoked
      potential (SEP) recording before surgery and ten weeks after decompression.
      Compression of the spinal nerves induced changes in the SEP which persisted for
      up to ten weeks after decompression, but it had no effect on the final
      neurological outcome. Our study shows the importance of early surgical
      decompression for cauda equina syndrome.

PMID- 9250764
TI  - Periprosthetic bone remodelling after cementless total hip replacement. A
      prospective comparison of two different implant designs.
AB  - In a prospective study of 14 patients undergoing total hip replacement we have
      used dual-energy X-ray absorptiometry (DEXA) to investigate remodelling of the
      bone around two different designs of cementless femoral prosthesis. The bone
      mineral density (BMD) was measured at 12-weekly intervals for a year. Eight
      patients (group A) had a stiff, collarless implant and six (group B) a flexible
      isoelastic implant. Patients in group A showed a decrease in BMD from 14 weeks
      after operation. By 12 months, the mean loss in BMD was 27%, both medially and
      laterally to the proximal part of the implant. Those in group B showed an overall
      increase in BMD which reached a mean of 12.6% on the lateral side of the distal
      portion of the implant. Our results support the current concepts of the effects
      of stem stiffness and flexibility on periprosthetic remodelling.

PMID- 9250765
TI  - The anatomy of the anterior origin of the deltoid.
AB  - We studied the origin of the anterior deltoid from the lateral third of the
      clavicle and the leading anterior edge of the acromion in 18 cadaver shoulders by
      anatomical and histological methods. The main origin of the deltoid was from the
      superior surface of the anterior acromion, but muscle and tendinous attachments
      were also seen on the entire anterior surface of the acromion, its anteroinferior
      surface and on the whole width of the anterior surface of the clavicle. Mock
      arthroscopic acromioplasty was shown to detach deltoid fibres from the anterior
      surfaces, leaving the superior attachment in continuity. Potentially,
      arthroscopic subacromial and clavicular resection can detach deltoid fibres
      originating from the anterior and anteroinferior surfaces of the acromion and
      clavicle and thus weaken the anterior deltoid.

PMID- 9250766
TI  - The treatment of wrist instability.

PMID- 9250767
TI  - Fractures of the coracoid process.

PMID- 9250768
TI  - Unipolar or bipolar prosthesis for displaced intracapsular hip fracture.

PMID- 9250769
TI  - Simple bone cysts treated by percutaneous autologous marrow grafting.

PMID- 9250770
TI  - An evaluation of the Constant-Murley shoulder assessment.

PMID- 9250771
TI  - An evaluation of the Constant-Murley shoulder assessment.

PMID- 9250772
TI  - Care of the polytraumatised patient.

PMID- 9250773
TI  - Reamed or unreamed nailing for closed tibial fractures.

PMID- 9250774
TI  - Degenerative changes at the knee and ankle related to malunion of tibial
      fractures.

PMID- 9250775
TI  - Neutralization of hemolytic and mouse lethal activities of C. perfringens alpha
      toxin need simultaneous blockade of two epitopes by monoclonal antibodies.
AB  - Three murine monoclonal antibodies (MAbs 3B4, 1E8, 1F9) were produced by fusion
      of X63-Ag8.653 myeloma cells and splenocytes of mice immunized with
      glutaraldehyde-inactivated alpha-toxin of Clostridium perfringens. All MAbs
      belonged to the immunoglobulin G (IgG) class and possessed a kappa light chain.
      All the MAbs were specific for alpha-toxin of C. perfringens as demonstrated by
      immunoblotting experiments performed with culture supernatants of C. perfringens,
      C. bifermentans, C. sordellii, and Bacillus cereus. Competition analysis in an
      ELISA revealed that the MAbs recognized different epitopes on the alpha-toxin
      molecule. In an immunoblot assay based on a recombinant protein expressed in
      Escherichia coli, the binding site of MAb 1E8 but not those of MAbs 3B4 and 1 F9
      were mapped to the COOH-terminal fragment of alpha-toxin (aa 248-370). To prove
      the neutralizing potential of the MAbs, alpha-toxin was preincubated with MAbs
      and subsequently tested for its lecithinase activity in an egg yolk diffusion
      turbidity (EYDT) assay, its hemolytic activity in a hemolysis test, and its
      lethal effect on mice after intraperitoneally administration. When the MAbs were
      tested individually, neutralization was only seen in the EYDT assay, where MAb
      3B4 completely abolished the lecithinase activity of alpha toxin. However, when
      MAbs 3B4 and 1 E8 were used in combination, they acted synergistically and
      inhibited the lysis of rabbit erythrocytes in vitro. The same mixture of MAbs was
      also able to completely neutralize the lethal effect of three LD50 of alpha-toxin
      on Balb/c mice. Our results suggest that the alpha-toxin molecule contains
      several domains which are differently involved in the various activities of the
      toxin. We conclude that the hemolytic domain(s) of alpha-toxin is (are) identical
      with or very closely located to the domain(s) that cause the mouse lethal effect.
      The lecithinase activity may be involved in the mechanisms of hemolysis and mouse
      lethality but appears not to be the only determinant.

PMID- 9250776
TI  - Heat shock response of Streptococcus pneumoniae: identification of immunoreactive
      stress proteins.
AB  - In order to investigate whether pneumococcal heat shock proteins (HSPs) were
      major immunogens of humoral immune response, we first characterized the heat
      shock response of S. pneumoniae. Three HSPs, HSP62, HSP72 and HSP80, having an
      apparent molecular mass of 62, 72, and 80 kDa, respectively, were detected by
      labelling proteins synthesized with [35S]methionine after a shift from 37 degrees
      C to 45 degrees C and fluorography of SDS-polyacrylamide gels.
      Radioimmunoprecipitation and immunoblot analyses with mouse anti-pneumococcal
      sera revealed that HSP72 was a major immunogen. S. pneumoniae HSP62 was another
      antigen which was precipitated by some immune sera. Anti-HSP72 antibodies
      appeared after the first immunization with S. pneumoniae antigens and subsequent
      immunization elicited a booster response. Monoclonal antibodies (MAbs) to
      pneumococcal HSP72 were produced and their specificities defined. The epitopes
      reactive with four MAbs are highly conserved in S. pneumoniae since 20 out of 20
      different strains were recognized by each individual MAb. Western blot analysis
      revealed cross-reactivities with few non-pneumococcal strains. By N-terminal
      sequence analysis, the S. pneumoniae HSP72 was found to belong to the heat shock
      protein 70 family. That HSP72 is an important highly conserved antigen in S.
      pneumoniae should provide a basis for further investigation of its physiological
      and potential pathogenic role.

PMID- 9250777
TI  - Host modulation of tissue destruction caused by periodontopathogens: effects on a
      mixed microbial infection composed of Porphyromonas gingivalis and Fusobacterium
      nucleatum.
AB  - These studies determined the ability of selected periodontopathogens to
      synergistically initiate soft tissue destruction in a murine abscess model. The
      development of immunity following recovery from infection or by active
      immunization was also examined. Mice were infected with P. gingivalis W50, F.
      nucleatum T18, or a combination of the two microorganisms. F. nucleatum caused
      only a localized lesion in contrast to P. gingivalis which caused a spreading
      suppurative inflammatory lesion of the skin and subcutaneous tissues, which,
      depending upon the dose, could result in death. Infection of mice with a
      combination of P. gingivalis and F. nucleatum elicited a significantly greater
      lesion size (P<0.001) and lethality compared with P. gingivalis alone. Mice
      infected with a subclinical dose (no visible lesion) of P. gingivalis failed to
      develop protective immunity to a secondary P. gingivalis challenge. Mice that had
      recovered from P. gingivalis lesions demonstrated partial protection against
      subsequent P. gingivalis challenge; however, the immunity was less protective
      against the mixed F. nucleatum + P. gingivalis infection. Active immunization
      with P. gingivalis protected against both the P. gingivalis and F. nucleatum + P.
      gingivalis challenges and this protection was correlated with the levels of
      specific serum immunoglobulin G (IgG) antibody. The results indicated that the
      murine model is ideally suited to examine bacterially-mediated mixed infections
      that result in soft tissue destruction. This destruction can be minimized, but
      not abrogated, with development of immunity. Challenge with sufficient numbers of
      the pathogens can overwhelm the acquired immunity.

PMID- 9250778
TI  - Macrophage antigen-1 positive cells are essential in the defense against
      Theiler's virus strain GD VII infection in the spinal cord.
AB  - Acute encephalomyelitis caused by Theiler's virus strain GD VII resembles human
      poliomyelitis, and T cells are essential in eliminating the virus from the brain,
      though not from the spinal cord. We speculated that macrophage-lineage cells
      might play a crucial role in eliminating the virus from the spinal cord. To
      analyse the role of macrophage-lineage cells in the infection, antibodies
      specific for beta2 integrin, as well as an anti-leukocyte function antigen 1 (LFA
      1) monoclonal antibody (MAb) and an anti-complement receptor type 3 (CR3) MAb
      were used to deplete the corresponding cell populations in Theiler's virus
      infected mice. Infiltration of CD8+ T cells into the brain and spinal cord was
      inhibited by the administration of the anti-LFA-1 MAb, and viral replication was
      augmented only in the brain. The number of CD4+ T cells and macrophage antigen-1
      (Mac-1[+]) cells in the brain and spinal cord were not decreased by anti-LFA-1
      MAb treatment. Anti-CR3 MAb treatment led to decrease of Mac-1(+) cells in the
      brain and spinal cord. The viral replication in the spinal cord of anti-CR3 MAb
      treated mice was augmented, but not that in the brain. These results indicate
      that the defense mechanism against Theiler's virus strain GD VII is dependent on
      Mac-1(+) cells in the spinal cord.

PMID- 9250780
TI  - The role of O1-antigen in the adhesion to uroepithelial cells of Klebsiella
      pneumoniae grown in urine.
AB  - We obtained mutants devoid of the O1-antigen, the capsular polysaccharide (K
      antigen) or both from Klebsiella pneumoniae clinical isolates (urinary
      infection). These mutants were grown in urine, and their ability to fimbriate and
      to adhere were studied. Mutants lacking the O1-antigen, independently of the
      other surface molecules (capsule and fimbriae), showed a great decrease in
      adhesion to these cells.

PMID- 9250779
TI  - A gerbil model for rhombencephalitis due to Listeria monocytogenes.
AB  - Rhombencephalitis due to Listeria monocytogenes is a frequent complication of
      human listeriosis, inducing a high mortality and severe neurological sequelae
      despite antibiotic therapy. However, there is no animal model which consistently
      reproduces clinical rhombencephalitis. Here, we present a model of Listeria
      rhombencephalitis in gerbils. Animals were inoculated in the middle ears with a
      low infective dose of L. monocytogenes, thus creating prolonged otitis media with
      persistent bacteremia. Gerbils developed a severe rhombencephalitis with circling
      syndrome, paresia, ataxia, rolling movements. The invasion of the central nervous
      system was visualized on living animals by resonance magnetic imaging and
      characterized by bacterial growth in the brain, reaching about 10(7) bacteria in
      the rhombencephalum by day 12 of infection. The histological lesions were mainly
      located in the brainstem, and consisted in coalescent, necrotic abscesses with
      perivascular sheaths, mimicking those observed in human rhombencephalitis.
      Bacteria were detected by electronmicroscopy inside infectious foci, either free
      in necrotic material or inside inflammatory cells, mainly polymorphonuclear
      cells. This gerbil model of Listeria rhombencephalitis will be useful to study
      the molecular mechanisms allowing bacteria to cross the blood-brain barrier, and
      to evaluate the intracerebral efficacy of antibiotics.

PMID- 9250781
TI  - Extracellular release by Trichomonas vaginalis of a NADP+ dependent malic enzyme
      involved in pathogenicity.
AB  - This report presents evidence showing that Trichomonas vaginalis releases in the
      extracellular environment a functional form of NADP(+)-dependent malic enzyme.
      The protein which is likely responsible for the oxidative decarboxilase activity
      had already been identified in previous studies as P65, one of the five adhesive
      proteins of the protozoan. The same protein had also been described as AP65 by
      other authors, which identified it as one of the four surface proteins
      specifically responsible for binding of the parasite to the target cell in a
      ligand-receptor fashion. Gene characterization studies performed on P65 by
      different authors revealed that the nucleotide sequences of the genes coding for
      P65 display a striking homology with the ones coding for the trichomonad malic
      enzyme. The experiments performed in this work demonstrate that P65 is secreted
      and retains its adhesive properties in the extracellular environment, being able
      to bind both erythrocytes and HeLa cells. Therefore, an oxidative decarboxylase
      activity assay was performed on T. vaginalis cell-free filtrates, in order to
      assess if the released P65 displays cathalitic properties. The assay revealed
      that parasite-free supernatants exhibit an oxidative decarboxylase activity which
      is NADP(+)-dependent. On the basis of the most recent findings on T. vaginalis
      pathogenetic mechanism, which involves pH-dependent perforins, a role for the
      secreted enzyme as part of the system is proposed.

PMID- 9250782
TI  - Late infections following allogeneic bone marrow transplantation: suggested
      strategies for prophylaxis.
AB  - Bone marrow transplant recipients remain at risk for infections for a variable
      period of time even after adequate hematologic reconstitution. Late infections
      are a significant cause of morbidity and can be fatal in 4-15% of these patients.
      Patients with chronic graft versus host disease (GVHD) and unrelated-donor
      transplant recipients, even without GVHD, are at particular risk. Most late
      infections occur in the first post-transplant year, the majority are caused by
      bacteria, particularly encapsulated organisms, or herpes group viruses (CMV and
      VZV) and present with cutaneous, sino-pulmonary or systemic involvement.
      Effective chemoprophylaxis is available only for the encapsulated bacteria
      (penicillin or erythromycin) and Pneumocystis carinii
      (trimethoprimsulfamethoxazole). Routine use of long-term I.V. immunoglobulin
      supplementation has not been shown to be effective and may be harmful as it may
      delay reconstitution of humoral immunity. Active immunization (pneumococcal
      vaccine, influenza vaccine and HiB) can be effective in patients more than 6-12
      months from transplant who do not have GVHD. In this review we present our
      experience, a summary of published literature on the subject of late infections
      in bone marrow transplant patients and offer guidelines for preventative
      strategies.

PMID- 9250783
TI  - In vitro and in vivo biologic effects of interleukin-3 (IL-3) in follicular low
      grade lymphoma.
AB  - Interleukin-3 (IL-3) is a pleiotropic cytokine which has stimulatory effects on a
      broad range of hematopoietic progenitor cells. These effects have led to the use
      of IL-3 in clinical trials for the treatment of aplastic anemia and
      myelodysplastic syndrome as well as to stimulate bone marrow recovery in patients
      who have received high-dose therapy and bone marrow/stem cell transplantation.
      However, because one study suggested that IL-3 may also stimulate the growth of
      follicular small cleaved cell lymphoma (FSCCL) cells in vitro, it was concerning
      that the use of IL-3 after bone marrow transplantation in patients with FSCCL may
      stimulate the growth of undetectable minimal residual tumor cells resulting in
      early relapsed disease. In contrast to these observations, our own in vitro
      studies demonstrated that IL-3 inhibited FSCCL cells in short-term culture in a
      dose-dependent manner. Subsequently, we conducted a phase II clinical trial using
      single agent IL-3 for the treatment of patients with follicular low grade
      lymphoma. Our clinical data did not support the hypothesis that IL-3 is a growth
      stimulator of FSCCL.

PMID- 9250784
TI  - Coexpression of lymphoid and myeloid markers on cell surfaces.
AB  - Cells coexpressing lymphoid and myeloid cell surface markers have been described
      for various leukemias and non-Hodgkin's lymphomas. It is unclear whether these
      mixed lineage characteristics are due to malignancies of early progenitor cells
      or alternatively to malignant cells with lineage infidelity. Recently, it has
      been shown that cells coexpressing lymphoid and myeloid markers can be generated
      from peripheral blood lymphocytes from normal individuals as well. In this
      review, consequences of this surprising fact are discussed.

PMID- 9250785
TI  - p21WAF1 mutations and human malignancies.
AB  - During the past few years, several categories of cyclin-dependent kinase
      inhibitors (CDKIs), which negatively regulate cyclin/cyclin-dependent kinase
      (CDK) activities, were cloned. The p21WAF1, also known as CIP1 or SDI1, was the
      first reported CDKI: it's expression is induced by wild-type p53. The p21WAF1 is
      a potent inhibitor of most cyclin/CDK complexes and also inhibits the ability of
      the proliferating cell nuclear antigen (PCNA) to activate DNA polymerase d.
      Alterations of the cell-cycle can cause cellular transformation. We analysed 471
      primary samples from 15 types of human malignancies and 36 cell lines for
      structural alterations of the p21WAF1 gene. No changes were found in the coding
      region of p21WAF1 gene by polymerase-chain reaction-single-strand conformation
      polymorphism (PCR-SSCP) analysis. Many of these tumors had a normal p53 gene.
      Other investigators showed that p21WAF1 knockout mice did not have an increased
      incidence of cancer, while p53 knock-out mice did. Taken together, the absence of
      alterations of p21WAF1 in a series of malignancies suggests that p21WAF1 may not
      have a role in either onset or progression of most human cancers. Furthermore,
      p53 probably activates additional, critical tumor suppressor pathways.

PMID- 9250786
TI  - Tretinoin tocoferil as a possible differentiation-inducing agent against
      myelomonocytic leukemia.
AB  - Tretinoin tocoferil is an alpha-tocopherol ester of all-trans retinoic acid
      (ATRA) and safely used to treat skin ulcers. Tretinoin tocoferil stimulates the
      formation of granulation tissue in the ulcer, and enhances the migration of
      guinea pig macrophages and stimulates the proliferation of human skin
      fibroblasts. These effects are different from those of either ATRA or alpha
      tocopherol. Tretinoin tocoferil induces the granulocytic differentiation of human
      promyelocytic leukemia HL-60 cells, and more than additively enhances cellular
      differentiation induced by sub-optimal concentrations of ATRA. Tretinoin
      tocoferil and ATRA synergistically inhibit the proliferation of HL-60 cells,
      suggesting that tretinoin tocoferil acts differently than ATRA on leukemia cells.
      Tretinoin tocoferil also enhances the differentiation of HL-60 cells induced by
      dimethyl sulfoxide, phorbol ester and 1alpha,25-dihydroxyvitamin D3(VD3).
      Tretinoin tocoferil and VD3 synergistically inhibit the proliferation and induce
      the differentiation of other myelomonocytic leukemia cells. Toxicity tests in
      animal models have shown that tretinoin tocoferil is at least 150 times less
      toxic than ATRA and does not induce teratogenesis. Therefore, the combination of
      tretinoin tocoferil and VD3 may be useful for treating myelomonocytic leukemia.

PMID- 9250787
TI  - Primary parotid lymphoma: the effect of International Prognostic Index on
      outcome.
AB  - Since the reported survival and failure-free survival (FFS) of adults with
      primary parotid non-Hodgkin's lymphoma (NHL) is variable, we reviewed our
      experience of untreated adults with primary parotid NHL. Patients were eligible
      if they presented to the University of Texas M. D. Anderson Cancer Center Cancer
      between 1980 and 1995 with parotid enlargement and if the diagnosis of lymphoma
      was verified according the Working Formulation. Medical records were reviewed to
      determine Ann Arbor Stage (AAS), the International Prognostic Index (IPI) score,
      response to therapy, relapse, FFS, and survival. We identified 39 untreated
      adults with primary parotid NHL representing 1% of all lymphomas and 8.6% of all
      untreated parotid neoplasms. Three patients were excluded because of suboptimal
      therapy, leaving 36 patients eligible for outcome analysis. Of the 18 patients
      with low-grade NHL, two were treated with radiotherapy, eight with chemotherapy
      and radiotherapy, seven with chemotherapy only, and one with antibiotics. The
      complete remission (CR) rate was 94%, and with a median follow-up of 36 months
      for surviving patients the survival and failure-free survival (FFS) at 5 years
      were 94% and 78%, respectively. The 5-year FFS were not statistically different
      between patients with early (I or II) or advanced (III or IV) AAS (83% and 74%,
      respectively; p > 0.05) and favorable (0 or 1) or unfavorable (> 1) IPI scores
      (73% and 100%, respectively; p > 0.05). All 18 patients with intermediate-grade
      NHL were treated with doxorubicin-based chemotherapy which was followed by
      radiotherapy in six. The CR rate was 89%, and with a median follow-up of 51
      months for surviving patients the survival and FFS at 10 years were 80% and 72%,
      respectively. In this group 10-year FFS was better in early than in advanced AAS
      (100% vs 0%, respectively; p = 0.01) and in favorable (0 or 1) than in
      unfavorable (> 1) IPI scores (86% vs 20%, respectively; p < 0.01). We conclude
      the the FFS of patients with low-grade NHL is 78% and not affected by AAS or IPI
      score. The FFS of patients with intermediate-grade NHL appears comparable with
      that of NHLs of other primary sites, being 86% for those with IPI < or = 1 and
      20% for those with IPI 1. Patients with IPI > 1 should be entered on
      investigational protocols aiming to increase FFS.

PMID- 9250788
TI  - Expression of BCR-ABL, E2A-PBX1, and MLL-AF4 fusion transcripts in newly
      diagnosed children with acute lymphoblastic leukemia: a Children's Cancer Group
      initiative.
AB  - We used reverse transcriptase polymerase chain reaction (RT-PCR) assays to
      examine primary leukemic cells in on-study diagnostic bone marrow specimens from
      642 children with newly diagnosed acute lymphoblastic leukemia (ALL) for the
      expression of MLL-AF4, E2A-PBX1, and BCR-ABL fusion transcripts. All PCR assays
      were performed centrally in the Children's Cancer Group ALL Biology Reference
      Laboratory. MLL-AF4 transcript was found in only 0.7% of the study population
      which excluded infants. E2A-PBX1 transcript was found in 2.5% of the study
      population and 3.3% of B-precursor cases. Expression was associated with massive
      hepatomegaly. BCR-ABL transcript was found in 2.3% of cases and correlated with
      older age, induction failure, and inferior event-free survival (EFS). RT-PCR
      assays allow rapid identification of patients with MLL-AF4 and BCR-ABL positive
      ALL. These patients have a poor outcome with contemporary therapy and rapid
      identification facilitates timely allocation to innovative treatment programs.

PMID- 9250789
TI  - Taxol pretreatment of tumor targets amplifies natural killer cell mediated lysis.
AB  - Taxol is known to polymerize and stabilize microtubules and thereby alter many
      cellular functions. Our studies examined the effects of taxol pretreatment of
      tumor targets and cytotoxic effector cells in an effort to determine whether such
      treatment would result in increased tumor cell lysis without affecting cytotoxic
      cell function. Our studies demonstrated that taxol concentrations of 6-30 ng/ml
      which induced approximately 50% growth inhibition and > or = 50% block in the
      G2/M phase of the K562 cell targets did not have any significant effect on the
      functional ability of NK cells to lyse K562 cells. Pretreatment of K562 cells
      with taxol (6 and 30 ng/ml) resulted in an increase in K562 cell lysis by NK
      cells (or NK cells stimulated with 100 units/ml of rIL-2) in 7 out of 9 donors.
      The amplification of NK cell-mediated lysis of tumor targets due to taxol
      pretreatment may provide a combination therapeutic approach which includes taxol
      treatment followed by rIL-2 stimulation of the immune killer cell function.

PMID- 9250790
TI  - Phase I study of fludarabine and paclitaxel for the treatment of low-grade non
      Hodgkin's lymphoma.
AB  - We conducted a phase I clinical trial of a new combination of fludarabine and
      paclitaxel in which 19 patients with histologically confirmed recurrent low-grade
      non-Hodgkin's lymphoma (NHL) were treated at five dose levels. Fludarabine was
      administered intravenously by bolus for 5 days and paclitaxel was given by
      intravenous (I.V.) continuous infusion for 96 or 72 hours starting day 1. Courses
      were repeated every 4 weeks. Patients whose disease responded received a maximum
      of six courses. All 19 patients received at least one course and could be
      evaluated for toxic effects, and 18 patients could be evaluated for response. The
      maximum tolerated dose (MTD) was 20 mg/m2/day I.V. bolus for 5 days of
      fludarabine plus 60 mg/m2/day I.V. of paclitaxel given as a continuous infusion
      over 72 hours. The limiting toxic effect was neutropenic fever, which was
      observed in five of the seven patients treated at the highest dose level. Grade 3
      non-hematologic toxic effects of stomatitis (14%), neuropathy (14%), and
      hypotension (14%) were also observed at the highest dose level. No grade 4 non
      hematologic toxic effects or treatment-related deaths occurred. One patient had
      herpes zoster infection of the skin 1 year after the completion of therapy. The
      overall response rate was 50%, with the two patients whose disease completely
      responded remaining disease free at 22 and 17 months. Patients with no prior
      exposure to either paclitaxel or fludarabine had 62% response rate. We conclude
      that the combination of fludarabine and paclitaxel appears to have promising
      activity for the treatment of recurrent low-grade NHL.

PMID- 9250791
TI  - Antimicrobial prophylaxis to prevent opportunistic infections in patients with
      chronic lymphocytic leukemia after allogeneic blood or marrow transplantation.
AB  - Opportunistic infections have been a problem after BMT in CLL. We have
      allografted seven patients with B-CLL (n = 6) or B-prolymphocytic leukemia (n =
      1) from matched siblings (n = 6) or a mismatched unrelated donor (n = 1). Amongst
      the first six, we saw two cases of recurrent or prolonged cytomegaloviremia and
      CMV disease, one listeria meningitis, and one fatal toxoplasma encephalitis. The
      latter two developed in the setting of steroid therapy of GVHD with extensive
      prior fludarabine therapy. Prophylaxis for opportunistic infections was developed
      on an ongoing basis as new infectious complications were seen. The current drug
      prophylaxis, which has been successful for eight months in the last patient
      despite pretreatment with fludarabine and steroid therapy for GVHD, is directed
      against pneumocystis, toxoplasma, fungi, and pneumococci. It includes
      immunoglobulin (for 3 1/2 months), pyrimethamine-sulfadiazine (for 4 months and
      during steroids), fluconazole (for 2 1/2 months), cotrimoxazole or pentamidine
      (for 2 years) and penicillin (lifelong). Dietary precautions are followed for 4
      months and during steroids to prevent listeriosis. Four patients are alive in
      remission with no active infectious problems 8-44 months (median 29) after BMT.
      We recommend adoption of these or similar prophylactic measures for BMT in CLL as
      a baseline which can be modified if new infections are identified and according
      to individual needs.

PMID- 9250792
TI  - 2-Chlorodeoxyadenosine in cutaneous T-cell lymphoproliferative disorders.
AB  - The efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in cutaneous T-cell
      lymphoproliferative disorders was examined. Between February 1991 and April 1996,
      25 patients with relapsed or refractory cutaneous T-cell lymphoproliferative
      disorders (24 mycosis fungoides or Sezary syndrome, one Ki-1+ anaplastic large
      cell lymphoma) were treated with 2-CdA initially administered by continuous
      intravenous infusion at a dose of 0.1 mg/kg/d for 7 days (13 patients). The
      infusion duration was subsequently reduced to 5 days (9 patients) because of
      prohibitive hematologic toxicity. Three patients were treated at the same daily
      dose by bolus injection over two hours for 5 days. Cycles were administered at 28
      day intervals. Seventeen patients received more than one cycle. An overall
      response rate of 24% was achieved. Three patients (12%) had a complete response
      with a median duration of 4.5 months (range, 2.5 to 16). Three (12%) had a
      partial response with a median duration of 2 months (range, 2 to 4). Nineteen
      patients (76%) had no response. The most significant toxicities encountered were
      myelosuppression (64%) and infectious complications (64%). 2-CdA has activity as
      a single agent in patients with previously treated relapsed T-cell
      lymphoproliferative disorders.

PMID- 9250793
TI  - Activity of 2-chlorodeoxyadenosine (Cladribine) in 2-hour intravenous infusion in
      94 previously treated patients with low grade non-Hodgkin's lymphoma.
AB  - The purpose of our study was to determine the efficacy of 2-chlorodeoxyadenosine
      (2-CdA) administered in 2-hour intravenous infusions in previously treated
      patients with low grade non-Hodgkin's lymphoma (LGNHL). We treated 94 LGNHL
      patients with 2-CdA at a dosage of 0.12 mg/kg/24h in 2-hour intravenous infusion
      for 5 consecutive days. The treatment consisted of from 1 to 7 courses (median
      3), repeated usually at monthly intervals. All patients were refractory to or
      relapsed after standard chemotherapy. Of these 94 patients 78 (83%) had clinical
      stage IV of the disease. Complete response (CR) was obtained in 12 (12.8%) and
      partial response (PR) in 36 (38.3%) giving an overall response rate of 51.1%. In
      12 (12.8%) grade 4 thrombocytopenia with haemorrhagic diathesis was noted, grade
      4 neutropenia was observed in 12 (12.8%) and infections complicated the course of
      treatment in 38 (40.4%) patients. 2-CdA treatment was the cause of death of 3
      patients. The results of our study show that 2-CdA given in 2-hour infusions is
      an effective agent in advanced, heavily pretreated patients with LGNHL.

PMID- 9250794
TI  - Somatostatin receptor scintigraphy in the staging of lymphomas.
AB  - In this prospective study we evaluated the somatostatin receptor scintigraphy in
      the initial staging of 19 patients suffering from Hodgkin's (HD) and non
      Hodgkin's lymphomas (NHL) and in the restaging of 16 patients. Scintigraphy was
      compared to the results of the methods applied for adequate staging of lymphoma
      patients in the large multicentre trials. Planar imaging and SPECT was performed
      after intravenous injection of 110 or 220 MBq of 111In-pentetreotide. The patient
      based analysis yielded an overall sensitivity of 88%, contrasting lesion-based
      sensitivities of 57%, 35%, and 43% in HD, low-grade NHL and high-grade NHL,
      respectively. The best results were obtained in the head-and-neck region and the
      worst in the abdomen (sensitivities of 61% and 24%, respectively). Bone marrow
      infiltration was visible in 1/12 cases only. There was no significant difference
      between the outcomes of patients in the initial staging and restaging and no
      influence of the amount of injected radiopharmaceutical on the results. In terms
      of the Ann-Arbor classification, 10/35 patients were concordant whereas 22 were
      understaged and 3 overstaged scintigraphically. In conclusion, somatostatin
      receptor scintigraphy is not useful in the initial staging or restaging of
      malignant lymphomas, especially NHL, due to low lesion detection rates most
      probably because of low receptor densities. In addition, intraindividual
      heterogeneity of somatostatin receptor expression has to be considered.

PMID- 9250795
TI  - Evaluation of Taxol cytotoxicity on B-CLL cells in vitro.
AB  - Taxol is a new antimicrotubule agent that, besides a well known efficacy against
      solid tumors, has shown activity in non-Hodgkin's lymphomas too. We therefore
      investigated its in vitro cytotoxic activity against cells from patients affected
      by chronic lymphocytic leukemia (CLL). Peripheral blood lymphocytes from 46 CLL
      patients were incubated for four days with Taxol at doses ranging from 0.01 to 10
      mM and the cytotoxicity was evaluated by a colorimetric method (XTT). In most
      samples Taxol was inactive and the IC50 was > 10 mM in 40 out of 46 patients. It
      is worthwhile noting that four of the six in vitro responsive patients had
      unfavourable clinical features. In three unresponsive patients we also observed
      that Taxol was not able to induce apoptosis in vitro. In conclusion, based on in
      vitro data, it seems that Taxol is not an active drug in standard CLL but we
      cannot exclude some efficacy in other more rapidly proliferating
      lymphoproliferative disorders.

PMID- 9250796
TI  - Recurrence of Hodgkin's disease after 10 or more years: late relapse or de-novo
      malignancy due to HLA-DPB1*0301-linked susceptibility?
AB  - Recurrences of Hodgkin's disease (HD) ten or more years after initial therapy are
      rare and heterogeneous concerning pathological, biological and clinical features.
      Though usually regarded as relapses of initial disease at least part of these
      late recurrences may represent de-novo HD due to an increased constitutional
      risk. Following recent reports genetic risk for HD may be linked to the HLA
      DPB1*0301 allele. Therefore, we investigated DPB1 and other HLA class I and II
      gene loci in three patients with very late recurrences of HD presenting at our
      institution within the last two years. All patients carry the HD susceptibility
      allele HLA-DPB1*0301. The expected probability of three patients with HD
      displaying the HLA-DPB1*0301 phenotype by chance is only p = 0.022. As serologic
      investigations also revealed Epstein-Barr virus (EBV) activity in all three cases
      our results support a role of genetic susceptibility possibly leading to impaired
      immune responses to EBV in very late recurring HD. Additionally, HLA-DPB1*0301
      may be valuable for identifying patients with HD who might be candidates for a
      long term follow-up.

PMID- 9250797
TI  - The role of hepatitis C virus in the aetiology of non-Hodgkins lymphoma--a
      regional association?
AB  - Infection with the Hepatitis C virus (HCV) has been aetiologically linked with
      the lymphoproliferative disorder mixed cryoglobulinaemia and more recently with
      certain subgroups of B cell non-Hodgkin's lymphoma (NHL). Many of the studies
      which have documented the association with NHL have originated from Italy, where
      the background prevalence of infection with the virus is relatively high. We have
      performed a study, based in the West of Scotland, to determine the prevalence of
      infection with HCV in an unselected group of 110 individuals with
      lymphoproliferative disorders (72 with NHL, and 38 with chronic lymphocytic
      leukaemia). None of our cohort (both NHL and CLL) had evidence of infection with
      the virus. Our study suggests that whilst HCV may be important in the aetiology
      of certain subgroups of NHL, this effect may be regional and dependent upon the
      background prevalence of the virus in the community.

PMID- 9250798
TI  - Amplification of third-complementary-determining-region (CDR-III) of heavy chain
      immunoglobulin gene (IgH) in one hundred adult acute leukemias.
AB  - We applied a simple polymerase chain reaction (PCR) based method for detecting
      immunoglobulin heavy-chain (IgH) gene rearrangement, using its CDR-III region to
      assess B-cell clonality in a series of 100 acute lymphoblastic leukemias (ALL)
      (84 B-cell lineage, 4 null-ALL and 12 T-ALL). The amplified CDR-III regions can
      be generated in all the B-lineage ALL and separated by size by polyacrylamide gel
      electrophoresis (PAGE), thereby providing a specific diagnostic marker for each B
      cell clone. Size heterogeneity resulting from independent IgH rearrangement
      events and the high resolution power after electrophoresis and silver staining of
      the PAGE gels can be used to generate a "fingerprint" of the PCR fragments
      representing either the spectrum of B-cell clonality in complex populations of B
      lymphocytes or the partially genomic configuration of the VH-N-DH-N-JH region. At
      diagnosis, we found the presence of one clonal IgH heavy-chain gene rearrangement
      in 80 B-cell lineage and null ALL and a biclonal rearrangement in 8 cases. The
      CDR-III bands were of sizes ranging from 80 to 130 bp. The PCR analysis of the
      IgH gene enabled us to obtain a CDR-III leukemia specific product in all cases,
      thereby providing a specific and diagnostic marker for each B-cell clone.

PMID- 9250799
TI  - Rapid disappearance of AML1/ETO fusion transcripts in patients with t(8;21) acute
      myeloid leukemia following bone marrow transplantation and chemotherapy.
AB  - To assess the clinical significance of monitoring minimal residual disease in
      t(8;21)(q22;q22) AML, RT-PCR assay was conducted during the clinical course of 12
      patients who had undergone BMT or conventional chemotherapy. Two cases relapsed
      after BMT and chimeric RNA was detected soon after BMT in their bone marrow
      cells. The other three cases, in whom chimeric RNA was not detected after BMT,
      are in CR at 21 to 33 months following BMT. Similarly, four out of 7 cases who
      showed negative chimeric RNA after completion of chemotherapy have been in CR at
      11 to 34 months following completion of chemotherapy. The present findings appear
      different from other studies which reported the detection of AML1-ETO chimeric
      RNA in long-term CR patients.

PMID- 9250800
TI  - Granulocyte colony-stimulating factor (G-CSF, filgrastim) after or during an
      intensive remission induction therapy for adult acute lymphoblastic leukaemia:
      effects, role of patient pretreatment characteristics, and costs.
AB  - An early intensive anthracycline therapy can improve therapeutic outcome in adult
      acute lymphoblastic leukaemia (ALL) but is usually associated with marked
      myelosuppressive effects and significant morbidity by infections. To reduce this
      risk, we employed granulocyte colony-stimulating factor (G-CSF, filgrastim 5
      microg/kg/d) as an adjunct to a myelotoxic, 14-day long induction regimen with
      idarubicin-vincristine-L-asparaginase-prednisone (IVAP). Owing to changes in
      study design, patients received 'late' (n = 28) or 'early' (n = 37) G-CSF from
      days 15 or 4 of IVAP, respectively, until resolution of severe neutropenia. Study
      endpoints included time to recovery from neutropenic nadir, duration of
      neutropenia <0.5 x 10(9)/l, incidence of infectious complications, assessment of
      variables affecting G-CSF response, clinical outcome and costs. Sixty-five
      consecutive cases were evaluable. Patients in early G-CSF group recovered
      significantly faster from the neutropenic nadir (p < 0.002), contracted less
      infectious complications (p = 0.007), and required less intravenous antibiotic (p
      = 0.008) and antifungal (p = 0.002) medications. Although these reductions did
      not compensate for the increased G-CSF treatment cost, the overall supportive
      care cost was not significantly increased by early G-CSF. Interestingly, T-ALL
      phenotype (p = 0.02) and higher neutrophil presentation count (p = 0.03) were
      associated with a shorter neutropenic course even with late G-CSF. Early G-CSF
      may be a valid approach to mitigate chemotherapy-induced neutropenia of IVAP and
      other similarly myelosuppressive adult ALL regimens.

PMID- 9250801
TI  - Kinetics of humoral response in children with acute lymphoblastic leukemia
      immunized with influenza vaccine in 1993 in Poland.
AB  - A total of 49 children with acute lymphoblastic leukemia were immunized with a
      purified subvirion trivalent influenza vaccine (Wyeth-USA) and monitored for
      hemagglutination inhibition (HI) and neuraminidase inhibition (NI) antibodies
      before vaccination, and then three weeks and six months after vaccination.
      Results for HI antibodies were evaluated as geometric mean titre (GMT), mean fold
      antibody increase (MFI), protection and response rates and those for NI
      antibodies as geometric mean titre (GMT) and mean fold antibody increase (MFI).
      Six months after vaccination GMT for hemagglutinin 1 (H1) was much higher than
      previous values. GMT for hemagglutinin 3 (H3) and hemagglutinin B (HB) was lower
      than three weeks after vaccination, but much higher than the original values. In
      the control group GMT for H1 was on a low level all the time and for H3 and HB it
      was lower when compared with the original values. The proportion of vaccines to
      antibodies > or = 40 ranged between 45% and 88%. Six months after vaccination GMT
      for neuraminidase 1 (N1) increased when compared with the second sampling; for
      neuraminidase 2 (N2) and neuraminidase B (NB) it was slightly lower. In the
      control group GMT for all antigens was on a low level all the time. The results
      point to a significant seroconversion for both components after vaccination when
      compared with the control group.

PMID- 9250802
TI  - Clinical factors predictive of bone marrow involvement in Hodgkin's disease.
AB  - The role of bone marrow biopsy in the staging of Hodgkin's disease is undergoing
      reevaluation. We have studied the relationship of clinical factors to the
      presence of bone marrow involvement in 130 previously untreated patients with
      Hodgkin's disease. The presence of fever, spleen enlargement, anemia, leukopenia,
      poor performance status and poor histologic subgroups were positively correlated
      with the presence of bone marrow involvement in the univariate analysis. In the
      multivariate analysis, only fever, spleen involvement, leukopenia and poor
      histologic subgroups were significant. The predictive value of the absence of
      fever in regard to the absence of bone marrow involvement was 98%. The likelihood
      of bone marrow involvement in the absence of all four significant factors was
      only 0.05%. Patients without these clinical factors should probably not be
      submitted to a bone marrow biopsy as part of the staging procedures performed in
      Hodgkin's disease.

PMID- 9250804
TI  - Slimming diet and the development of acute leukemia: a possible relationship?
      Report of three cases.
AB  - Diet may play a key role in the pathogenesis of cancer and evidence for the role
      of a reduced intake of micronutrients with antioxidant properties have been
      increasingly reported. Until now, epidemiologic research in humans has focused on
      the negative effect of different diets containing excessive caloric intake and
      relatively little is known on the possible correlation between slimming diets and
      the incidence of acute leukemia. In this report we describe the temporal
      association of imbalanced slimming regimens and the subsequent diagnosis of acute
      leukemia in three cases. This association may be coincidental or perhaps suggests
      a possible relationship of the diet with the development or progression of acute
      leukemia.

PMID- 9250803
TI  - Absence of human herpes virus 8 DNA sequences in large granular lymphocyte (LGL)
      leukemia.
AB  - The etiology of large granular lymphocyte (LGL) leukemia is uncertain. Recently,
      a Kaposi's sarcoma-associated herpes virus, denoted as human herpes virus 8 (HHV
      8), has been identified. Some data suggest that HHV-8 and Epstein-Barr virus
      (EBV) may interact to induce malignant transformation. Infection with EBV has
      been implicated in the pathogenesis of some cases of LGL leukemia. Therefore, we
      performed PCR analyses for HHV-8 detection in samples from nineteen patients with
      LGL leukemia; three of these samples contained the EBV genome. We could not
      detect HHV-8 sequences in any of these patients. Therefore, HHV-8 infection is
      not involved in the pathogenesis of T-LGL leukemia.

PMID- 9250805
TI  - Sequential interphase FISH analysis of m-BCR/ABL chimeric gene-positive cells in
      Ph-positive acute myeloid leukemia.
AB  - We report a case of Philadelphia (Ph)-positive AML in which interphase
      fluorescence in situ hybridization (FISH) analysis was performed from diagnosis
      throughout the course of therapy using major (M-) breakpoint cluster region
      (BCR)/minor (m-) BCR and ABL cosmid probes. We also investigated the existence of
      the M-BCR or m-BCR at the RNA or DNA level by the reverse transcriptase
      polymerase chain reaction and Southern blot analysis, respectively. Complete
      remission with a normal karyotype was achieved after several regimens of
      chemotherapy and peripheral blood stem cell transplantation (PBSCT), but relapse
      occurred and his cells became 100% Ph-positive. We detected the m-BCR/ABL fusion
      gene by interphase FISH analysis using an m-BCR/ABL translocation probe, and
      found that FISH analysis was useful for classifying the BCR, identifying minimal
      residual disease, and for predicting imminent relapse after chemotherapy and
      PBSCT.

PMID- 9250806
TI  - Non-Hodgkin's lymphoma presenting with coagulopathy due to anti-phospholipid
      antibody syndrome.
AB  - The clinical presentation of non-Hodgkin's lymphoma (NHL) has been well
      recognized and characterized. Among the unusual presentations immunological and
      autoimmune phenomena have been reported. We describe a patient in whom NHL
      presented with lupus anticoagulants. The immunological and coagulation
      abnormalities at presentation and the complication during the course of NHL as
      well as their prognostic implication are discussed.

PMID- 9250807
TI  - Lymphoid myelofibrosis associated with high grade B cell lymphoma of the liver:
      morphological, cytogenetic, and clinical features.
AB  - Severe pancytopenia associated with moderate hepatosplenomegaly, increased serum
      lactic dehydrogenase (LDH) levels, and hypogammaglobulinemia were found in a
      young male patient. Bone marrow histology showed extensive fibrosis, hypoplasia
      of erythro- and granulocytopoiesis, and hyperplasia of megakaryocytopoiesis
      associated with histiocytic fat cell phagocytosis and infiltration of abnormal
      lymphocytes, compatible with lymphoid myelofibrosis. Striking chromosomal
      aberrations indicating karyotype evolution were also demonstrated by cytogenetic
      analyses (47, XY, +3 / 47, XY, +3, 1p+ / 46, XO, +3, 1p+, -Y). The clinical
      course was characterized by cyclic febrile episodes accompanied by excessive
      increase of serum LDH levels and leukocyte counts, and decrease of platelet
      counts, followed by spontaneous regression. Further diagnostic procedures,
      including two liver biopsies and computed tomography, did not detect any
      manifestation of lymphoma. Eventually, the patient developed rapidly progressive,
      lethal pulmonary aspergillosis. At autopsy, high grade B cell lymphoma of the
      liver was found. In this case, the lymphoid myelofibrosis seen on bone marrow
      biopsy may be considered as a manifestation of "discordant" bone marrow histology
      related to high grade lymphoma. With respect to the cyclic clinical course, a
      possible role of apoptotic mechanisms in the physiopathology of this disorder is
      reviewed.

PMID- 9250809
TI  - Deafness in chronic myeloid leukemia.

PMID- 9250808
TI  - Improving the cytogenetic response to interferon alpha by zidovudine (AZT) in an
      HIV-positive chronic myelogenous leukemia patient.
AB  - An asymptomatic HIV-positive patient with Philadelphia chromosome positive
      chronic myelogenous leukemia (CML) was treated by interferon-a (IFN-a) for four
      years. A sustained hematological response and major cytogenetic response were
      achieved. However, a complete cytogenetic remission (100% Ph-negative cells) was
      observed when zidovudine (AZT) was introduced as treatment for HIV-related
      immunodepression. Moreover, this complete cytogenetic remission was confirmed by
      quantitative PCR showing decreased BCR-ABL rearrangement at very low level. As,
      there are some in vitro reports demonstrating a synergistic antiproliferative
      effect of IFN-a and zidovudine, we discuss the possibility of synergistic effects
      between AZT and IFNa in the treatment of CML.

PMID- 9250810
TI  - Expression of sialosyl-T and disialosyl-T antigens in erythroid cells.
AB  - Expression of T, sialosyl-T and disialosyl-T antigens on normal blood and bone
      marrow cells as well as transformed cells was examined using specific monoclonal
      antibodies and multidimensional flow cytometry. Both anti-sialosyl-T (QSH1) and
      anti-disialosyl-T (QSH2) monoclonal antibodies aggregated erythrocytes. The anti
      disialosyl-T antibody was specific for the erythroid lineage and did not react
      with neutrophils, monocytes or T-lymphocytes, while the anti-sialosyl-T antibody
      reacted with erythroid cells and a subset of T-lymphocytes. The developing
      erythroid cells in bone marrow showed coordinate expression of glycophorin A and
      the two carbohydrate chains, sialosyl-T and disialosyl-T. Analysis of neoplastic
      cells showed that the anti-disialosyl-T antibody only reacted with glycophorin A
      positive blasts from erythroleukemia (FAB M6) patients (4/4) and one patient with
      chronic myeloid leukemia in erythroblastic transformation (CMLET). Leukemic
      blasts from these patients demonstrated coordinate quantitative expression of
      glycophorin A and disialosyl-T. The anti-sialosyl-T antibody reacted with
      glycophorin A-positive blasts from FAB M6 patients (4/4) and one CMLET patient;
      however, the antibody also reacted with glycophorin A-negative blasts from one
      FAB M6 and the one CMLET patients and transformed cells from other types of
      leukemia. The anti-T monoclonal antibody (HH8) did not react with any of the
      other cells tested. These results indicate that glycophorin A and disialosyl-T
      expression are tightly linked during normal erythroid development and erythroid
      leukemogenesis.

PMID- 9250811
TI  - CD11c integrin gene promoter activity during myeloid differentiation.
AB  - The integrin CD11c/CD18 functions as a cell surface receptor for numerous soluble
      factors and proteins (LPS, fibrinogen, iC3b), mediates leukocyte interactions
      with other cell types and is a signal transducing receptor. CD11c/CD18 is found
      primarily on myeloid cells, where its expression is regulated both during
      differentiation and during monocyte maturation into tissue macrophages. To
      determine the transcription factors and cis-acting elements driving the
      developmentally-regulated expression of CD11c/CD18 the proximal regulatory region
      of the CD11c gene has been structurally and functionally characterized using the
      U937 and HL-60 cell lines as myeloid differentiation models. The tissue-specific
      activity of the CD11c promoter is conferred by two Sp1-binding sites and an
      adjacent C/EBP-binding element, with a likely contribution from other
      transcription factors with a more limited tissue distribution (PU.1, Oct-2, Myb).
      The participation of Sp1 in the transcription of the CD11c gene strongly suggests
      that CD11c/CD18 expression is dependent on the proliferative state of the cell,
      thus establishing a first level of control for the regulated expression of
      CD11c/CD18 during myeloid differentiation. The differentiation responsiveness of
      the CD11c promoter has been mapped to an AP-1-binding site whose mutation greatly
      decreases the inducibility of the promoter during the PMA-triggered
      differentiation of U937 cells. Although AP-1 mediates the responsiveness to
      several other differentiating agents including GM-CSF, additional elements are
      required for induction of the CD11c promoter activity upon Sodium Butyrate
      triggered differentiation. In fact, the Sodium Butyrate-responsiveness and the
      presence of both AP-1- and C/EBP-binding sites suggests that the proximal
      regulatory region of the CD11c promoter might include an extracellular matrix
      response element. As a whole, the transcription of the CD11c gene appears to be
      controlled by the proliferative state of the cell and is tightly coupled to
      progression along the myeloid differentiation pathway. The differentiation
      inducibility of the CD11c promoter has been further demonstrated after stable
      transfection into U937 cells, where the -361/+43 fragment retains the capacity to
      drive luciferase expression upon PMA-, GM-CSF- or Sodium Butyrate-triggered
      myeloid differentiation. Thus, while the characterization of the transcription
      factors regulating CD11c expression is still in progress, the CD11c promoter has
      been shown to constitute a very useful tool for the identification of myeloid
      differenting agents which might be of potential therapeutical interest.

PMID- 9250812
TI  - Retinoid resistance in leukemic cells.
AB  - Recent studies have shown that a high proportion of patients with acute
      promyelocytic leukemia (APL) achieve complete remission after treatment with all
      trans retinoic acid (RA). Nevertheless, despite an initial good response, most
      patients who received continuous treatment with all-trans RA relapsed and develop
      RA-resistant disease. The detailed mechanisms for this development of RA
      resistance by APL cells are still unclear. Several possible mechanisms have been
      considered to explain in vitro resistance to RA. One obvious explanation is the
      generation of new mutations in the retinoid receptors. However, UF-1 cells (the
      first permanent APL cell line with RA-resistant features) had no point mutations
      in the ligand-binding domain of the RAR-alpha gene. Another potential mechanism
      for clinical RA resistance is the pharmacologic alteration in the metabolism of
      all-trans RA. Continuous treatment with all-trans RA in APL is associated with a
      progressive reduction of the plasma concentrations of RA. Induction of cytochrome
      P-450, cellular RA-binding protein (CRABP) and P-glycoprotein resulted in lower
      plasma and cellular levels of active retinoids. Thus, acquired resistance to RA
      may be explained at least in part by drug metabolism in leukemic cells.

PMID- 9250813
TI  - Wilms tumor gene expression in acute myeloid leukemias.
AB  - The Wilms' tumor gene product (WT-1) is suggested to act as a tumor suppressor in
      childhood malignancies of the kidney and as a transcription factor with
      regulating activity on a number of growth and differentiation factors. Wt-1 has
      been shown to be expressed in blast cells of the vast majority of patients with
      acute myeloid and lymphoblastic leukemias (AL) by a number of workers. High
      levels of wt-1 mRNA expression in blast cells of newly diagnosed AML patients
      predict worse prognosis when compared to patients with no or low wt-1 mRNA
      expression. Patients achieving complete responses after chemotherapy usually lose
      detectable signals of wt-1. In relapse of the disease reoccurrence of wt-1 mRNA
      can be determined in almost all patients with initially detectable wt-1 mRNA.
      Using sensitive techniques such as reverse transcription polymerase chain
      reaction (RT-PCR) relapses are preceded by wt-1 expression in some cases.
      Although a subpopulation of normal hematopoietic precursor cells has also been
      shown to express message for wt-1, detectable levels of wt-1 during follow-ups in
      AML patients have been shown to be useful as a marker for residual blast
      populations or even to predict relapse of AML. Whether the high level of wt-
      expression is a non-specific phenomenon resulting from malignant transformation
      or whether it has an impact on the pathophysiology of AML or the uncontrolled
      growth of AML blasts is still controversial. However, there are indicators for an
      involvement of wt-1 in malignant events of AML blasts such as the downregulation
      of wt-1 in chemically induced differentiation of AML blast cell lines or the
      interactions of wt-1 with the protooncogene bcl-2 and the tumor suppressor gene
      p53. In conclusion, its possible relevance as an AML marker and its role in
      pathophysiological mechanisms in AML will still have to be defined in the future.

PMID- 9250814
TI  - Infection of blood and bone marrow cells with the human cytomegalovirus in vivo.
AB  - The human cytomegalovirus (HCMV) is a major pathogen in immunocompromised
      patients. Both, primary infection and reactivation of latent virus can cause
      disease. Peripheral blood leukocytes (PBL) most likely play an important role in
      viral persistence and dissemination of infection. However, an open question has
      been whether HCMV actively replicates in PBL in vivo and whether the progenitor
      cells in the bone marrow are also infected. Previous studies on this issue are
      controversial. Here we summarize data on the tropism of HCMV for mature leukocyte
      populations as well as bone marrow progenitor cells during HCMV viremia. All cell
      populations were highly purified by a fluorescence activated cell sorter (FACS)
      and analyzed by PCR for the presence of viral genomic DNA. Moreover, mature
      leukocyte populations were investigated for mRNA expression of regulatory and
      viral structural proteins. We could show, that HCMV DNA was detected most
      frequently in granulocytes and monocytes as well as in CD34+ progenitor cells of
      immunosuppressed patients. Viral mRNA expression was found in granulocytes,
      monocytes, and lymphocyte fractions. In contrast, no HCMV DNA was found in
      healthy, seropositive individuals.

PMID- 9250815
TI  - Microsatellite instability in hematologic malignancies.
AB  - Malignant transformation in humans occurs via different mechanisms including the
      activation of oncogenes and/or loss of tumor suppressor genes. Recently, DNA
      mismatch repair defects manifest as genome wide microsatellite instability have
      been described as an additional mechanism of tumorgenesis in humans. Tumors
      exhibiting widespread microsatellite instability as first described in studies of
      hereditary nonpolyposis colorectal cancer (HNPCC) are referred to as having a
      mutator or replication error (RER+) phenotype. Until recently, the occurrence of
      microsatellite instability has been primarily characterized in solid neoplasms.
      Several reports have now identified this mutator phenotype in a number of
      leukemias and lymphomas as well. This loss of DNA replication repair function may
      lead to increased mutations in genes critical to normal cell growth regulation
      and ultimately tumor initiation and/or progression.

PMID- 9250816
TI  - Analysis of chimerism following allogeneic bone marrow transplantation by
      fluorescent-in-situ hybridization.
AB  - Twelve patients (9 males and 3 females) with chronic myelogenous leukemia,
      underwent CD8+ T cell depleted allogeneic bone marrow transplantation with a sex
      mismatched donor. To assess chimerism we performed fluorescent in-situ
      hybridization for the X and Y chromosome at different time points after BMT.
      Patient median age was 33 years (range, 27-48); median time to transplant was 28
      months (range, 5-87). All patients received thiotepa 10 mg/kg; cyclophosphamide
      120 mg/kg and 12.0 Gy of fractionated total body irradiation. CD8+ cells were
      depleted from the normal donor marrow with anti-CD8 murine monoclonal antibodies
      and immunomagnetic beads. Bone marrow aspirates were studied at <60, 60-140, 140
      300, and >300 days post BMT. Hybridization was done on mononuclear cells and a
      median of 518 cells were counted per slide with a fluorescent microscope. The
      median percentage of donor cells was 99.04%, 98.21%, 98.15%, and 99.52% at <60,
      60-140, 140-300, and >300 days after BMT. Mixed chimerism was a rare occurrence
      after CD8 depleted allogeneic BMT and occured only at low levels. Inhibition of
      repopulation by host hematopoietic cells may be associated with the graft-versus
      leukemia effect against CML.

PMID- 9250817
TI  - The use of a sequential high dose recombinant interleukin 2 regimen after
      autologous bone marrow transplantation does not improve the disease free survival
      of patients with acute leukemia transplanted in first complete remission.
AB  - We report the outcome of 50 consecutive patients with CR1 acute leukemia (AML =
      22; ALL = 28) treated with autologous BMT, after cyclophosphamide and TBI,
      followed with a sequential high dose rIL2 regimen. rIL-2 (RU 49637 from Roussel
      Uclaf, Romainville, France) was started after hematological reconstitution an
      average of 72 +/- 22 days post transplant. The schedule consisted of a continuous
      infusion over 5 cycles (Cycle 1: 5 days starting on day 1; cycle 2-5: 2 days
      starting on day 15, 29, 43 and 57). Patients were treated at 4 different dosages
      (12 (N = 40), 16 (N = 3), 20 (N = 2), 24 (N = 5) x 10(6) IU/m2/day). Toxicities
      were mainly related to capillary leak syndrome and thrombocytopenia. Patients
      received an average of 122 +/- 49 10(6) IU/m2. Two patients with AML died from
      toxicity. rIL-2 infusion was associated with very a high level of immune stimu
      lation of both T-cells (P < 0.05) and natural killer (NK) cells (P < 0.05) and
      associated cytolytic functions (P < 0.05). With a minimal and median follow-up of
      21 and 46 months, 3 year leukemia free survival is 41 +/- 6% overall, 39 +/- 10%
      and 43 +/- 8% for AML and ALL respectively. Relapse probabilities at 3 years are
      59 +/- 11% for AML and 57 +/- 8% for ALL. We conclude that this short infusion of
      rIL-2 over 2 months, resulting in an increased immune stimulation, is not
      associated with a better leukemic control for patients with acute leukemia
      transplanted early after reaching first complete remission.

PMID- 9250818
TI  - Autologous transplantation with CD52 monoclonal antibody-purged marrow for acute
      lymphoblastic leukemia: long-term follow-up.
AB  - During 1984-86, 23 patients (5-37 years, median 16) with acute lymphoblastic
      leukemia (ALL) in first remission (n = 11) or beyond (n = 12) underwent
      autologous transplantation (ABMT) using marrow purged with the rat anti-CD52
      monoclonal antibody Campath-1M after melphalan and total-body irradiation (TBI).
      Median time to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets was 38 and 51
      days respectively. Myeloid engraftment was significantly slower compared with ALL
      patients receiving unpurged marrow (P = .01). Eight patients died due to
      transplant-related causes 53-205 days after the procedure. Six of eight patients
      receiving 1150 cGy TBI died of toxicity compared with two of 15 receiving less
      than 1150 cGy (P = .006, Fisher's exact test). Nine patients relapsed at 45-195
      days (median 97); eight died and one is alive at nine years in a chemotherapy
      induced remission. Six patients are alive and well in continuous remission 9-10
      years (median 10) after transplant. The 10-year probabilities of disease-free
      survival and relapse are 26% (95% CI: 11-45%) and 51% (95% CI: 37-59%)
      respectively. We conclude that it is feasible to purge marrow for autografting
      using Campath-1M without killing normal stem cells. Myeloid engraftment is slow
      but consistent, and long-term survival is seen in a proportion of patients. The
      role of CD52 monoclonal antibodies for purging in ALL still requires further
      study.

PMID- 9250819
TI  - Variability in determination of body weight used for dosing busulphan and
      cyclophosphamide in adult patients: results of an international survey.
AB  - Fifty-two BMT institutions were sent a questionnaire asking for details of dosing
      for busulphan, cyclophosphamide (bu-cy), cyclosporin and methotrexate (CSA-MTX).
      The following data were requested: (a) the method used to determine the body
      weight for dosage calculations (b) the actual dose per weight and (c) the
      schedule of administration. Thirty-six (69%) institutions responded and 33 were
      evaluable. There was substantial variation in the method used to determine weight
      for bu-cy. No single method was used in more than 30% of units, although most
      units made some allowance for discrepancies between actual and ideal body weight.
      There was more uniformity in the method of weight determination for CSA-MTX, with
      the majority of units using actual body weight. Conversely, there was much more
      variation in the dose per weight formulae and schedules used for CSA-MTX than for
      bu-cy. These substantial differences highlight the importance of specifying these
      criteria when the toxicity and efficacy of chemotherapy regimens is reported and
      the need for further studies to determine the optimal weight formulae for dosage
      calculations.

PMID- 9250820
TI  - Prognostic value of cytogenetic abnormalities in previously untreated patients
      with non-Hodgkin's lymphoma.
AB  - In this study cytogenetic findings have been correlated with prognosis in 78
      previously untreated patients with non-Hodgkin's lymphoma (NHL) presenting
      between 1983 and 1988. The median follow-up was 7 years (range 2-9 years). There
      was no significant difference in the duration of survival of 33 patients with
      only abnormal karyotypes, 35 patients with a mixture of normal and abnormal
      karyotypes (AN) and 10 patients with only normal karyotypes (NN). This was true
      for the entire group (p = 0.6) as well as for the subsets of diffuse lymphomas
      (DL) and follicular lymphomas (FL) (p = 0.6 and 0.4, respectively). Monosomy 14
      was the only abnormality in the entire group of patients to be associated with a
      statistically significant difference in survival duration (p = 0.046). Among the
      FL patients, trisomy 7 (p = 0.046) and trisomy 12 (p = 0.010) were associated
      with shorter survival. Presence of t(14;18) did not influence survival in the
      entire group (p = 0.16), nor in any of the histological subgroups. Among the FL
      patients with t(14;18), presence of additional cytogenetic abnormalities was not
      associated with a worse outcome. The lack of consistency of results between
      various studies is likely to be due to several factors and the prognostic
      significance of karyotypic abnormalities can only be clarified by large
      prospective studies employing uniform treatment policies.

PMID- 9250821
TI  - Effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM
      CSF) on chemotherapy-induced myelosuppression in patients with chronic
      lymphocytic leukemia: a crossover study.
AB  - Patients with advanced, refractory chronic lymphocytic leukemia (CLL) have an
      high morbidity and mortality from infections following chemotherapy-induced
      myelosuppression. A crossover study on the prophylactic effect of GM-CSF therapy
      on neutropenia was carried out in 12 patients with advanced CLL. The patients
      received GM-CSF in association with every second cycle of COP (cyclophosphamide,
      vincristine, prednisone) chemotherapy. A total of 40 COP cycles were analyzed.
      Blood neutrophil levels were significantly higher two to three weeks after the
      first COP cycle followed by GM-CSF (medians 2.24 and 5.47 x 10(9)/l) when
      compared to the first cycle without GM-CSF support (0.59 and 0.75 x 10(9)/l; p <
      0.0195 and <0.002, respectively). In the next two cycles the same tendency
      persisted, although the difference was not statistically significant. There were
      no significant differences in the number of febrile days, days on intravenous
      antibiotics, hospitalization days, or the number of red blood cell transfusions.
      Mortality during COP treatment was 8%. In conclusion, GM-CSF efficiently
      ameliorates chemotherapy-induced neutropenia in CLL patients with a poor bone
      marrow reserve due to advanced disease.

PMID- 9250822
TI  - The chronic lymphocytic leukemia antigen (cCLLa) as immunotherapy target:
      pharmacokinetics and biodistribution of two divalent, ricin-based immunotoxins in
      xenografted athymic mice.
AB  - The chronic lymphocytic leukemia (CLL) antigen (cCLLa) is potentially suitable
      for targeted immunotherapy given its restriction to clonal CLL cells and lack of
      expression by normal lymphocytes. In order to assess the pharmacokinetics and
      biodistribution of two potent anti-cCLLa immunotoxins (ITs) were examined in the
      mouse model. The IgG fraction of anti-cCLLa monoclonal antibody CLL2m was
      conjugated with 125I-labeled intact (RTA) or deglycosylated (dgA) ricin chain A,
      injected intravenously into athymic mice engrafted with cCLLa-expressing human
      tumors, and monitored over 120 hours. Blood concentrations of CLL2m/125I-RTA and
      CLL2m/125I-dgA were best fit to biexponential equations but the latter exhibited
      a lower alphaT1/2 and betaT1/2 (4.1 and 102 min vs 5.9 and 126 min), a smaller
      volume of distribution (5.1 g vs 9.7 g), and a lower blood clearance (2.2 g/hr vs
      4.6 g/hr). Both ITs exhibited preferential tumor uptake that followed distinct
      kinetics: rising tumor uptake for 2 hrs post-injection (while tissue uptake
      decreased), reaching tumor/non-tumoral tissue uptake ratios up to 16.9; and
      slower dissociation rates of tumor- vs tissue-bound ITs (>45% vs <20% remaining
      tissue-bound 6 hrs post-injection, respectively). Non-specific liver uptake was
      not prominent for either IT. In vivo IT deconjugation reached 50% approximately
      12 hours pos-injection. The pharmacokinetics and biodistribution data in the
      mouse model suggest that ricin-based anti-cCLLa ITs are suitable for use in human
      trials.

PMID- 9250823
TI  - Pathways controlling the expression of surface CD21 (CR2) and CD23
      (Fc(epsilon)IIR) proteins in human malignant B cells.
AB  - The aim of the present study was to analyze the pathways regulating the
      expression of CD21 and CD23 B-cell differentiation antigens on human malignant B
      cells. Exposure of Farage cells, derived from a human B-cell lymphoma, to phorbol
      12-myristate 13-acetate (PMA) down-regulated CD21 and CD23 expression, while
      interleukin 4 (IL4) inhibited the expression of CD21 but augmented CD23
      expression. When Farage cells were stained with either anti-CD21 or anti-CD23
      monoclonal antibodies (mAb), subsequent exposure to IL4 failed to change the
      staining of the cells, indicating that IL4 did not affect the turnover of CD21
      and CD23 molecules. Inhibition of protein synthesis with cycloheximide (CXM) had
      no effect on the expression of CD21 molecules, but abrogated their down
      regulation by IL4, suggesting that IL4 induced the synthesis of proteins which
      modify the processing of CD21 molecules. The inhibitory effect of IL4 on the
      expression of CD21 and its augmentary effect on the expression of CD23 was
      abrogated by H7 (1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine), an inhibitor of
      serine protein kinase. Staurosporine, an additional inhibitor of serine kinases
      also abrogated the effect of IL4 on CD23 expression. H8 (N-(2-[Methylamino]ethyl)
      5-isoquinolinesulfonamide), a preferential inhibitor of protein kinases A and G,
      and genistein, an inhibitor of tyrosine kinases had no effect on IL4-induced
      modulation of CD21 and CD23 in Farage cells. The exposure of B-chronic
      lymphocytic leukemia (CLL) cells to PMA reduced the expression of CD21, but
      increased the expression of CD23. IL4 had no effect on the expression of CD21 on
      CLL-cells but strongly enhanced the level of CD23. H7, H8 and genistein each
      abrogated to a different extent the effect of IL4 on the expression of CD23 by
      CLL-cells. These data indicate that activation of serine/threonine kinases in
      malignant B cells inhibited the production of CD21 proteins, while different
      protein kinases appeared to be involved in up- and down-regulation of CD23 in
      different B lymphocytes.

PMID- 9250824
TI  - The chronic lymphocytic leukemia antigen (cCLLa) as immunotherapy target:
      assessment of LD50 and MTD of four ricin-based anti-cCLLa immunotoxins (ITs) in
      Balb/c mice.
AB  - The chronic lymphocytic leukemia (CLL) antigen (cCLLa) is a promising
      immunotherapy target given its disease-restricted expression, its highest
      prevalence among CLL surface antigens, and its lack of expression by normal T-
      and B-lymphocytes. The objectives of this study were to assess the 50% lethal
      dose (LD50) and the maximum tolerated dose (MTD) in Balb/c mice of four anti
      cCLLa immunotoxins (ITs) derived from the intact monoclonal antibody (MoAb) or
      its Fab fraction, each conjugated to either ricin chain-A (RTA) or its
      deglycosylated derivative (dgA). The IgG fraction of anti-cCLLa monoclonal
      antibody CLL2m and its Fab fraction were conjugated to RTA or dgA to generate
      four ITs: IgG/RTA, IgG/dgA, Fab/RTA and Fab/dgA. Progressive concentrations of
      each IT (ranging between 2.60 mg/kg and 100.00 mg/kg) were injected intravenously
      into groups of 5 mice each. After injection, mice were monitored daily for 10
      days for survival. Observed mortality data in each group were matched to those in
      Weil's tables for estimating LD50 (mg/kg) from the moving average interpolation
      method. Estimated LD50 (in mg/kg) were: IgG/RTA, 13.33; Fab/RTA, 25.53; IgG/dgA,
      55.33; Fab/dgA, 55.33. Their respective MTD (mg/kg), defined as the highest dose
      level survived by all mice, were 8.78, 13.17, 29.63 and 29.63. Depending on the
      animal-to-human extrapolation method used, the calculated LD50 and MTD in humans
      ranged from 1.2 mg/kg and 0.8 mg/kg (IgG/RTA), to 55.6 mg/kg and 36.9 mg/kg
      (IgG/dgA and Fab/dgA), respectively. The following conclusions are drawn. 1.
      Antibody valence exerted little influence on either the LD50 or the MTD; 2. The
      LD50 to MTD ratios were approximately 2:1; 3. dgA-derived ITs were approximately
      one half as toxic as their RTA-derived counterparts; and 4. Extrapolation of LD50
      and MTD mouse data to humans resulted in dose levels comparable to or exceeding
      those reported in most IT human trials. These data suggest the suitability of
      anti-cCLLa ITs for clinical immunotherapy trials.

PMID- 9250825
TI  - 11q13 rearrangement in B cell chronic lymphocytic leukemia.
AB  - Translocation t(11;14)(q13;q32) and/or 11q13 rearrangements have been reported in
      various B cell immunoproliferative disorders. They appear to be frequent in
      mantle cell zone lymphoma (MZL) and rare in B-cell chronic lymphocytic leukemia
      (B-CLL). Discrimination between MZL and B-CLL is sometimes uncertain on the basis
      of morphology and immunophenotype. To evaluate the incidence of 11q13
      rearrangements in B-CLL, purified B cells from 59 untreated patients were studied
      by cytogenetic methods after short term stimulated culture. Abnormalities at band
      11q13 were found in 2 cases only. Fluorescent in situ hybridization (FISH) study
      confirmed del(11)(q13) in one case and showed translocation t(11;13) in another
      one. Thus this rearrangement appears to be very rare in B-CLL and its finding
      should lead to a careful search for the characteristic features of MZL, namely,
      morphology, the expression of CD5 without CD23, high density monotypic SIg,
      together with t(11;14) and/or bcl-1/IgH rearrangement.

PMID- 9250826
TI  - Disease progression in patients with multiple myeloma is associated with a
      concurrent alteration in the expression of both oncogenes and tumour suppressor
      genes and can be monitored by the oncoprotein phenotype.
AB  - The dysregulation of specific oncogenes due to either mutation or activation has
      previously been reported in a small number of patients with myeloma but the
      extent of oncogene dysregulation during the course of the disease is not known.
      The oncoprotein phenotype of plasma cells in 146 bone marrow samples from 81
      patients with multiple myeloma was determined by dual colour flow cytometry using
      a predetermined panel of 8 monoclonal antibodies. High intensity CD38 expression
      was used to distinguish the plasma cell population and the cells were
      permeabilised to detect intracellular antigen expression. In situ hybridization
      using biotinylated cDNA probes for c-myc and bcl-2 was used to determine mRNA
      expression and to validate the flow cytometric assay. The normal range of
      expression for each of 6 oncoproteins (c-myc, c-fos, c-neu, bcl-2, p-ras, p53
      mutant) and 2 tumour suppressor gene products (p53 wild and Rb) was determined in
      plasma cells from 33 normal bone marrows. Disease progression was associated with
      the concurrent abnormal expression of at least one oncogene and one tumour
      suppressor gene where as stable disease was associated with a normal expression
      of at least one or both (chi2 = 34.1; p < 0.001). At diagnosis there was a
      correlation between serum beta2 microglobulin and the concurrent overexpression
      of both an oncoprotein and a tumour suppressor gene product. Longitudinal studies
      of 33 different patients over 4 years, suggests that the progressive evolution of
      myeloma is a multistep process of genomic instability producing ongoing
      alterations in the expression of both oncogenes and tumour suppressor genes.

PMID- 9250827
TI  - A phase I study of interleukin-6 after autologous bone marrow transplantation for
      patients with poor prognosis Hodgkin's disease.
AB  - We performed a pilot study of human recombinant IL-6 (SDZ ILs 969) in 6 patients
      with poor prognosis Hodgkin's disease following autologous bone marrow
      transplantation (ABMT) to determine its safety and tolerability. IL-6 was
      administered the day following bone marrow infusion by subcutaneous injection
      once daily at a dose of 1 micro/kg/day to 3 patients and 2.5 microg/kg/day to 3
      patients and was continued for 6 weeks or until platelet engraftment (>50 x
      10(9)/L independent of transfusion). No severe or life threatening toxicities
      were seen at either dose level. A reversible elevation in alkaline phosphatase
      occurred in 4 patients and all patients complained of headache, myalgias, and
      fever. Gastrointestinal toxicity was low, grade 3-4 mucositis occured less
      frequently than in similarly-treated historical controls receiving GM-CSF. Serum
      concentrations of other cytokines such as IL-3 and G-CSF after ABMT differed from
      results obtained in transplant recipients given GM-CSF. The median time to an ANC
      >0.5 x 10(9)/L was 25.5 days and to a platelet count of >20 x 10(9)/L independat
      of transfusion was 35.5 days. Engraftment was no different from controls. Five
      patients relapsed at a median of 5 months post-ABMT and four remain alive at a
      median of 12 months post-ABMT. We conclude that IL-6 administration is safe and
      well tolerated in patients following ABMT. Further efforts to evaluate its effect
      on hematopietic recovery as well as relapse following transplantation in a larger
      patient series are warranted.

PMID- 9250828
TI  - melphalan, single-fraction total-body irradiation and allogeneic bone marrow
      transplantation for acute leukemia: review of transplant-related mortality.
AB  - Causes of treatment-related death were studied amongst 138 patients with acute
      myeloid (n = 90) or lymphoblastic (n = 48) leukemia allografted from HLA
      identical siblings in first (n = 107) or second (n = 31) remission after a
      conditioning regimen comprising 110 mg/m2 melphalan and 1050 cGy single-fraction
      total-body irradiation (TBI) prescribed as maximum lung dose. Graft-versus-host
      disease (GVHD) prophylaxis consisted of cyclosporine (n = 78) or cyclosporine
      methotrexate (n = 60). Eighty-one patients died of causes other than relapse 16
      2917 days (median 77) after transplantation. The actuarial probability of non
      relapse mortality was 62% at 5 years. The major primary causes of death were
      pneumonitis (n = 38, 47%), GVHD (n = 18, 22%), and sepsis (n = 11, 14%).
      Pneumonitis contributed to 42 of the deaths (52%), and its etiology was infective
      (n = 27), idiopathic (n = 14), or a combination of the two (n = 1). On
      multivariate analysis, GVHD prophylaxis with cyclosporine alone was associated
      with a higher overall toxic death rate. The use of cyclosporine alone and a low
      infused cell dose (<2.5 x 10(8) total nucleated cells/kg or <0.6 x 10(8)
      mononuclear cells/kg) were associated with a higher risk of death from
      pneumonitis. We conclude that the use of cyclosporine alone as GVHD prophylaxis
      is associated with increased transplant-related toxicity, and the addition of
      methotrexate and infusion of a higher number of cells decrease the incidence of
      fatal pneumonitis.

PMID- 9250829
TI  - Biphenotypic blast crisis of chronic myelogenous leukemia: abnormalities of p53
      and retinoblastoma genes.
AB  - The molecular mechanisms responsible for progression of chronic myelogenous
      leukemia (CML) to blast crisis have not been well defined. Blast crisis may be
      partially related to inactivation of tumor suppressor genes/such as p53 or
      retinoblastoma (Rb) gene. There is evidence for an association of blast cell
      phenotypes in CML with alterations of these genes: a strong association of
      myeloid phenotypes with abnormalities of the p53 gene and a weaker association of
      lymphoid phenotypes with abnormalities of the Rb system. We found a marked
      decrease in Rb gene product and rearrangements of the p53 gene simultaneously in
      two cases of biphenotypic blast crisis of CML (myeloid and B-lymphoid). These
      results support the association of blast cell phenotypes with alterations in
      tumor suppressor genes in CML blast crisis.

PMID- 9250830
TI  - Treatment of relapsed adult acute lymphoblastic leukemia with fludarabine and
      cytosine arabinoside followed by granulocyte colony-stimulating factor (FLAG
      GCSF).
AB  - The aim of the present study was to evaluate the efficacy of the combination of
      fludarabine 30/mg/m2 + cytarabine 2g/m2 followed by the administration of G-CSF
      to achieve a complete remission (CR) in patients with relapsed acute
      lymphoblastic leukemia (ALL). We treated twelve patients in first relapse,
      overall 10 patients achieved a second CR, one patient showed resistant disease
      and one patient died during remission induction. The regimen was well tolerated
      and we observed a short period of neutropenia with a low incidence of
      myelosuppression-associated problems. Eight patients in second CR received the
      same chemotherapeutic regimen as consolidation used for the reinduction. In six
      patients the chemotherapeutic regimen was well tolerated, two patients died,
      (cerebral hemorrhage in one patient and sepsis in the other). In conclusion the
      combination of fludarabine, cytarabine and G-CSF has significant antileukemic
      activity and non hematological toxicities were acceptable. The addition of G-CSF
      reduced the period of neutropenia obtaining a low incidence of myelosuppression
      associated problems.

PMID- 9250831
TI  - De novo acute myeloid leukemia with near-pentaploidy: diploid karyotype and
      lymphoblastic phenotype at relapse.
AB  - Hyperploidy is a rare finding in leukemias, with isolated cases of tetraploidy
      reported in acute myeloblastic and acute lymphblastic leukemias. We report the
      first case of acute myeloid leukemia with near-pentaploidy (5 n+/-) which was
      present in 100% of metaphases at diagnosis. By light microscopy, the leukemic
      blasts were exceptionally large and coarsely granulated. Following one cycle of
      induction chemotherapy, complete morphologic and cytogenetic remission was
      documented. Four weeks later relapse occured, at which time the karyotype was
      diploid and the morphological and immunophenotypic characteristics were those of
      a lymphoid leukemia. However, the presence of three aberrant chromosomes (5q+,
      6q+ and 20q+) confirmed that this was clonal evolution of the original myeloid
      leukemia. To the best of our knowledge, this case represents the first report of
      near-pentaloidy in de novo, pretreatment human leukemia.

PMID- 9250832
TI  - Systemic mast cell disease associated with hairy cell leukaemia.
AB  - Systemic mast cell disease (SMCD) can be regarded as a tumorous proliferation of
      tissue mast cells involving various organs. The frequency with which SMCD is
      found in patients with haematological disorders suggests that the association is
      non-random. The association includes primarily, myeloid disorders such as
      myelodysplastic syndromes and acute or chronic myeloproliferative disorders.
      Lymphoproliferative disorders may also occur but more rarely, mostly non
      Hodgkin's low grade B cell lymphomas. In this report a case is described in which
      SMCD occurred in a patient with hairy cell leukaemia.

PMID- 9250833
TI  - Spontaneous remission during two pregnancies in a patient with essential
      thrombocythaemia.
AB  - A woman with untreated essential thrombocythaemia (ET) exhibited spontaneous
      normalization of her elevated platelet count during two pregnancies. After
      delivery the platelet count increased rapidly to the same high level as before.
      Low platelet adhesion as well as adrenalin- and collagen-induced platelet
      aggregation, present before pregnancy, increased to normal values during
      pregnancy. Furthermore, no erythropoietin-independent colony growth was observed
      during pregnancy, while such colonies were clearly demonstrated when the patient
      was assayed after pregnancy. This is the second case in the literature
      demonstrating that remission of ET can occur without treatment during pregnancy.

PMID- 9250834
TI  - Subjective pain report and the outcome of several orthopaedic tests in
      craniomandibular disorder patients with recent pain complaints.
AB  - A comparison between a subjective pain report and the outcome of the combined
      dynamic and static pain tests, and several other orthopaedic tests, was
      investigated in craniomandibular disorder (CMD) patients with recent pain
      complaints and in control subjects. Thirty-two CMD patients who clearly reported
      pain in the masticatory muscle region or in the temporomandibular joint region by
      means of a symptom report questionnaire (SRQ), participated in the study. The
      investigators performing the symptom report interview and the clinical tests were
      blinded to each other. A high correspondence was shown between the patients
      reporting joint or muscle pain (by means of SRQ) and the classification into
      arthrogenous and myogenous pain patients, based on the outcome of the dynamic and
      static pain tests (P = 0.0003). The outcome of four other orthopaedic tests:
      passive maximum mouth opening (PMMO; P = 0.0001), palpation of the
      temperomandibular joint (TMJ) and the masticatory muscles (P = 0.0002), TMJ-play
      (P = 0.0001), and TMJ-compression (P = 0.0138) demonstrated significant
      differences between the patients reporting joint and muscle pain.

PMID- 9250835
TI  - A new method for assessing masticatory performance: a feasibility and
      reproducibility study.
AB  - The aim of this study was to develop a method for assessing masticatory
      performance based on incorporation of a colour binder in a test material with the
      presumption that the absorption of the colour is proportional to the total
      surface area of the masticated material. This was tested in vitro with erythrosin
      as the colour substance and Praestol 655BC as the colour binder incorporated into
      Satou's synthetic test material (equal amount of carnauba wax and
      bariumsulphate). The authors found that the difference in spectrophotometrical
      absorbance between a standard erythrosin solution and the supernatant of the same
      solution incubated half an hour with artificially pulverized test material was
      almost linearly correlated (r = 0.997) with the particle surface. This test
      material was then fabricated as small tablets and four adults chewed repeatedly
      five grams of these tablets to assess selectivity and reproducibility of the
      method. A good selectivity was found in that within the total range of the
      difference in absorbance (0.47-1.19) an inter-individual difference of more than
      0.17 is significant on a 95% level with double experiments. There were no
      differences in the intra-individual variation for double determinations between
      immediate repeat and 1 week interval performances but the reproducibility was
      disturbed when two subjects used their partial dentures.

PMID- 9250836
TI  - Amalgam marginal quality assessment: a comparison of seven methods.
AB  - Black's class I classic cavities were cut in 120 sound extracted human premolars
      and restored with one of two silver amalgams, six different base combinations,
      with or without cavity varnish and then aged for 3 months or 1 year. Thereafter,
      the restored teeth were subjected to a bacterial or acid broth in vitro carious
      challenge for 36 days. Resin cast impressions were made of the restoration margin
      of each specimen before and after the carious challenge giving a total of 240
      replicas. The replicas were examined in a scanning electron microscope (SEM) and
      the margins subjected to seven marginal assessment procedures: (i) ranking using
      micrographs of the margin; (ii) percentage length of marginal discrepancy; (iii)
      Mjor assessment using six groups; (iv) number of margin segments showing a
      discrepancy; (v) greatest gap size; (vi) ranking based firstly on gap size and
      then number of margin segments showing a discrepancy; and (vii) ranking based
      firstly on gap size and then percentage length of marginal discrepancy. The data
      from procedures (i), (ii), (vi) and (vii) were examined using one-way ANOVA; a
      linear logistic statistical analysis examined data from procedures (iii)-(v).
      Statistical significance was chosen at P < 0.05. It was found that procedure
      (vii) was able to discriminate between variables to a greater degree than all
      other procedures. It is recommended that a ranking system based on greatest gap
      size and percentage length of marginal discrepancy be used to assess marginal
      quality of amalgam restorations.

PMID- 9250837
TI  - Recognition of veneer restorations by dentists and beautician students.
AB  - Three types of veneer restorations (VRs) were evaluated for recognition by two
      groups of observers to study the aesthetic result. The different types of VRs
      were: porcelain, direct resin composite and indirect resin composite. One month
      after insertion of the VRs, colour transparencies were made of smiling patients
      randomly selected from a group of 112 patients participating in a clinical trial.
      The slides were evaluated by five dentists who were not familiar with the
      patients and by 25 beautician students (BS). Dentists were asked to locate the
      VRs which were present in the patients and to specify the type of VR. BS were
      only asked to locate the VRs. To trace a possible relationship between the
      aesthetic result of the treatment and a number of variables, ANOVA was applied to
      evaluate the variables: 'discolouration of the teeth' before treatment, 'type of
      VR' and 'number of VRs'. Agreements in judgement were expressed in Cohen-Kappa
      coefficients. The results showed that the dentists could locate the VRs quite
      well (Kappa coefficient 0.64 +/- 0.28) but for BS this was lower (Kappa
      coefficient 0.43 +/- 0.27). The more VRs were made in one patient, the more
      difficult it was to locate them correctly. The other variables had no significant
      effect on the recognition of the VRs. It was not possible for the dentist
      observers to differentiate between the types of VRs.

PMID- 9250839
TI  - Experimental wax mixtures for dental use.
AB  - Improvements in the properties of dental waxes were sought by alterations in
      their composition. Twenty-six blends of paraffin wax, beeswax and inorganic
      filler were subjected to the following tests: plastic deformation (flow), linear
      thermal expansion, elastic modulus and flexural strength. Flow tests were
      conducted in accordance with the corresponding ISO specification. Thermal
      expansion coefficients were estimated using thermomechanical analysis. Mechanical
      properties were tested using a universal testing machine. Pure paraffin and
      beeswax were used as controls. The results were subjected to analysis using
      correlation and regression. Regression coefficients in the range of 0.90-0.99
      were obtained in most cases, flow tests exhibiting the highest coefficients and
      flexural strength the lowest. The incorporated filler particles reduced the flow
      of the natural waxes, especially of the ester-containing beeswax, and improved
      the elastic modulus and strength. Good correlation was found between the
      ingredient proportions and measured properties, suggesting a relationship between
      them, although this is quite complicated in the case of tertiary wax mixtures.
      The experimental blends exhibited properties that are potentially useful for a
      range of clinical applications.

PMID- 9250838
TI  - Gonial angles and condylar and ramus height of the mandible in complete denture
      wearers--a panoramic radiograph study.
AB  - It has been accepted that the shape of the mandibular base, and especially the
      gonial angle of the mandible, correlates with the function of the jaw closing
      muscles. The gonial angles of the mandible and condylar and ramus heights of 30
      complete denture wearers (18 women, 12 men, mean age 61 years, range 42-74 years)
      coming for renewal of their dentures were measured using panoramic radiographs.
      The mean period of edentulousness was 26 years (range 10-53 years). No
      statistically significant difference was observed between the sexes in the the
      sizes of gonial angles and condylar and ramus heights. The right gonial angle was
      statistically significantly smaller than the left one and correlated negatively
      with the ramus height in both sides but positively with the increased EMG
      activity in the right masseter muscle. The size of the gonial angle and the
      condylar and ramus heights did not correlate with the age of the patients,
      edentulous period or alveolar ridge resorption.

PMID- 9250840
TI  - The effects of bolus size and chewing rate on masticatory performance with
      artificial test foods.
AB  - To better understand 'within subject' variability in masticatory performance of
      artificial food, this study evaluates the effects of bolus size and chewing rate.
      Twenty young adult male subjects each participated in two experiments evaluating
      their ability to process an artificial food (CutterSil). Based on the frequency
      distributions for the weights of the chewed particles, median particle size and
      broadness of the particle distribution were estimated. Controlling for the number
      of chews, the effect of (1) bolus size was evaluated by having each subject chew
      one whole tablet, four quarters, three quarters or two quarters; (2). chewing
      rate was evaluated by having the subjects chew first habitually, then at slow (40
      cycles/min) and fast (100 cycles/min) rates. The results showed that median
      particle sizes decreased and the distribution of particles widened with
      decreasing bolus size. The slow chewing rate produced the smallest particles with
      the widest distributions, followed by the habitual and fast rates, respectively.
      The study has shown that bolus size and chewing rate are important source of
      variation which must be considered in studies of masticatory performance.

PMID- 9250841
TI  - Studies on dental high-speed cutting of commercial pure titanium (Ti) and free
      machining titanium (DT-2F).
AB  - Some dental prostheses are formed by machining. The purpose of this study was to
      evaluate the dental high-speed cutting behaviour of free-machining titanium (Ti),
      the ease in cutting of which is metallurgically improved. Weight-load cutting
      tests were performed on commercial pure Ti and free-machining Ti, using a diamond
      point and a carbide burr. It became evident that the cutting effectiveness of two
      rotary cutting instruments on free-machining Ti was superior to that on
      commercial pure Ti due to the formation of accelerated cut debris. Cutting of
      free-machining Ti resulted in less damage of the carbide burr, compared with the
      cutting of commercial pure Ti. These results suggest that free-machining Ti is a
      suitable workpiece for dental Ti-based machined prostheses.

PMID- 9250842
TI  - The effect of potential investment expansion and hot strength on the fit of full
      crown castings made with phosphate-bonded investment.
AB  - In an earlier investigation, it was shown that when full crowns are cast in
      gypsum-bonded investments, their relative inaccuracy is affected by both the
      investment's potential expansion and its hot strength. This study repeated the
      earlier one, but used a high-melting gold alloy and two phosphate-bonded
      investments. The investments were used under conditions which gave a range of
      potential expansions and hot strengths. Casting inaccuracies were determined both
      diametrally and axially. All castings showed distortion, which varied under the
      different conditions. All were oversized axially, by amounts varying from + 0.8%
      to +2.3%. Diametral inaccuracies ranged from -0.2% to +0.7%. Investment expansion
      had a strong effect on axial inaccuracy, but a negligible effect on diametral
      inaccuracy. Conversely, hot strength had a strong effect on diametral inaccuracy,
      but only a very weak effect on axial inaccuracy. With phosphate-bonded
      investments, both potential expansion and hot strength are important parameters
      of relative casting inaccuracy. In combination, these properties showed very
      strong correlations with both diametral and axial inaccuracies. The observed
      distortions were the result of anisotropic mould expansion and anisotropic alloy
      shrinkage. The best fit, and least distortion, occurred with an investment
      setting under dry conditions.

PMID- 9250843
TI  - Trial of duplication procedure for complete dentures by CAD/CAM.
AB  - The purpose of this study was to duplicate the shapes of complete dentures by
      using a computer-aided design/manufacturing (CAD/CAM) system. The shapes of the
      complete dentures of an edentulous patient were measured using a non-contact type
      shape measurement system and morphological data at the interval of 0.25 mm were
      obtained in the X-axis and Y-axis directions. Measurement was performed from the
      occlusal surface and mucosal surface sides. Based on the three-dimensional
      morphological data, cutter paths for cutting were generated. For cutting, the
      three-step method consisting of rough cutting, finish cutting, and partial finish
      cutting was used and for duplicating the dentures the modelling wax was cut using
      a computerized numerical control (CNC) processor and ball-end mills with
      diameters of 6 mm and 1 mm. The method for the controlling of three axes (X, Y,
      and Z) of CNC machine was used, and cutting was performed only from two
      directions. Although further improvements are needed in the measurement and
      cutting in acute slope areas, the duplication of complete dentures appears to be
      possible using the CAD/CAM system.

PMID- 9250844
TI  - Condylar asymmetry and handedness in patients with temporomandibular disorders.
AB  - The relationship between condylar asymmetry and handedness of dentate patients
      with temporomandibular disorders was investigated. A group of 28 patients (22
      females and 6 males) was studied. The mean age was 28.29 years, with a range from
      10 to 54 years. The association between handedness and the sign of the condylar
      asymmetry index was examined using Fisher's exact test. No difference was found
      between sign and handedness (P > 0.05). This suggests that handedness does not
      affect the asymmetry index in this group of patients.

PMID- 9250845
TI  - The effect of changes in the consumption of macrolide antibiotics on erythromycin
      resistance in group A streptococci in Finland. Finnish Study Group for
      Antimicrobial Resistance.
AB  - BACKGROUND: In the early 1990s there was an increase in erythromycin resistance
      among group A streptococci in Finland. In response, policies regarding outpatient
      antibiotic therapy were changed, and nationwide recommendations were issued that
      called for reductions in the use of macrolide antibiotics for respiratory and
      skin infections in outpatients. We studied the effect of this policy on the
      pattern of erythromycin resistance throughout Finland. METHODS: From 1991 through
      1996, a total of 39,247 group A streptococcal isolates from throat swabs (82
      percent of the isolates) and pus samples (18 percent) and 290 isolates from blood
      cultures were studied in regional microbiology laboratories. The susceptibility
      of the isolates to erythromycin was tested by the disk-diffusion or the screening
      plate method. RESULTS: Consumption of macrolide antibiotics decreased from 2.40
      defined daily doses per 1000 inhabitants per day in 1991 to 1.38 in 1992
      (P=0.007) and remained near the lower level during the study period. The change
      in consumption was followed by a steady decrease in the frequency of erythromycin
      resistance among group A streptococcal isolates from throat swabs and pus
      samples, from 16.5 percent in 1992 to 8.6 percent in 1996 (odds ratio for 1996 as
      compared with 1992, 0.5; 95 percent confidence interval, 0.4 to 0.5).
      CONCLUSIONS: In Finland, after nationwide reductions in the use of macrolide
      antibiotics for outpatient therapy, there was a significant decline in the
      frequency of erythromycin resistance among group A streptococci isolated from
      throat swabs and pus samples.

PMID- 9250846
TI  - A comparison of low-molecular-weight heparin with unfractionated heparin for
      unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin
      in Non-Q-Wave Coronary Events Study Group.
AB  - BACKGROUND: Antithrombotic therapy with heparin plus aspirin reduces the rate of
      ischemic events in patients with unstable coronary artery disease. Low-molecular
      weight heparin has a more predictable anticoagulant effect than standard
      unfractionated heparin, is easier to administer, and does not require monitoring.
      METHODS: In a double-blind, placebo-controlled study, we randomly assigned 3171
      patients with angina at rest or non-Q-wave myocardial infarction to receive
      either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body
      weight, administered subcutaneously twice daily, or continuous intravenous
      unfractionated heparin. Therapy was continued for a minimum of 48 hours to a
      maximum of 8 days, and we collected data on important coronary end points over a
      period of 30 days. RESULTS: At 14 days the risk of death, myocardial infarction,
      or recurrent angina was significantly lower in the patients assigned to
      enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs.
      19.8 percent, P=0.019). At 30 days, the risk of this composite end point remained
      significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent,
      P=0.016). The need for revascularization procedures at 30 days was also
      significantly less frequent in the patients assigned to enoxaparin (27.1 percent
      vs. 32.2 percent, P=0.001). The 30-day incidence of major bleeding complications
      was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated
      heparin group, but the incidence of bleeding overall was significantly higher in
      the enoxaparin group (18.4 percent vs. 14.2 percent, P=0.001), primarily because
      of ecchymoses at injection sites. CONCLUSIONS: Antithrombotic therapy with
      enoxaparin plus aspirin was more effective than unfractionated heparin plus
      aspirin in reducing the incidence of ischemic events in patients with unstable
      angina or non-Q-wave myocardial infarction in the early phase. This benefit of
      enoxaparin was achieved with an increase in minor but not in major bleeding.

PMID- 9250847
TI  - Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal
      expansion of highly mutated germinal-center B cells.
AB  - BACKGROUND: The atypical cells of nodular lymphocyte-predominant Hodgkin's
      disease, designated lymphocytic and histiocytic (L&H) cells, have a B-cell
      phenotype. To clarify the clonality of these cells, we studied rearranged
      immunoglobulin genes for the variable region of the heavy chain (V[H] genes) in
      individual L&H cells from 11 patients with nodular lymphocyte-predominant
      Hodgkin's disease. We also studied the expression of immunoglobulin light chains
      by those cells in six of the same patients. METHODS: Single CD20+ L&H cells were
      isolated from frozen sections by a technique of micromanipulation. The rearranged
      V(H) genes of these cells were amplified by the polymerase chain reaction (PCR),
      sequenced, and compared with germ-line V(H) genes. Immunoglobulin light-chain
      messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Of 615 L&H
      cells isolated from all the frozen sections, 160 yielded PCR products. In each of
      the 11 patients, the L&H cells that could be evaluated had identically rearranged
      V(H) genes, whether they were isolated from the same nodule, different nodules,
      or different blocks of tissue. All the V(H) sequences derived from the L&H cells
      were highly mutated (7.5 to 27.2 percent). In two cases the coding capacity of
      the V(H) genes was completely or partially disrupted by mutations. Intraclonal
      diversity was found in six cases, and monotypic immunoglobulin light-chain mRNA
      was found in six. CONCLUSIONS: The L&H cells of nodular lymphocyte-predominant
      Hodgkin's disease represent a monoclonal expansion of B cells. The high load of
      V(H) gene mutations and signs of intraclonal diversity suggest a relation between
      L&H cells and germinal-center B cells at the centroblastic stage of
      differentiation.

PMID- 9250848
TI  - Clonality in nodular lymphocyte-predominant Hodgkin's disease.
AB  - BACKGROUND: There is general agreement that lymphocytic and histiocytic (L&H)
      cells, the variants of Reed-Sternberg cells in nodular lymphocyte-predominant
      Hodgkin's disease, belong to the B-cell lineage. However, the clonality of L&H
      cells remains controversial. METHODS: We used complementarity-determining region
      3 (CDR3) of the immunoglobulin heavy-chain gene as a clonal marker to study
      individual L&H cells isolated by micromanipulation from tissue sections of five
      patients with nodular lymphocyte-predominant Hodgkin's disease. The heavy-chain
      CDR3 of each cell was amplified by the polymerase chain reaction. The products
      were analyzed by gel electrophoresis, and representative amplification products
      from each patient were sequenced. RESULTS: L&H cells whose heavy-chain CDR3 was
      related, indicating the presence of a clonal population, were detected in all
      five patients and were the dominant population in three. In four of the five
      patients, members of the clone were found in different nodules in the tissue
      section, different tissue blocks from the same tumor, or different lymph nodes
      from the same patient. The CDR3 sequences in each clone frequently contained
      nucleotide substitutions indicative of intraclonal mutation. CONCLUSIONS: Clonal
      populations of L&H cells occur in nodular lymphocyte-predominant Hodgkin's
      disease. Intraclonal variation in nucleotide sequences suggests that
      hypermutation of the heavy-chain CDR3 continues to occur among the clonal
      progeny.

PMID- 9250849
TI  - The effect of antenatal phenobarbital therapy on neonatal intracranial hemorrhage
      in preterm infants.
AB  - BACKGROUND: The administration of phenobarbital to pregnant women before delivery
      has been thought to decrease the frequency of intracranial hemorrhage in preterm
      infants. To evaluate this potential neuroprotective therapy further, we
      determined the effect of antenatal administration of phenobarbital on the
      frequency of neonatal intracranial hemorrhage and early death. METHODS: We
      studied 610 women who were 24 to 33 weeks pregnant and who were expected to
      deliver their infants within 24 hours. The women were randomly assigned to
      receive either phenobarbital (10 mg per kilogram of body weight) or placebo
      intravenously, followed by maintenance doses until delivery or 34 weeks of
      gestation. The infants born to these women underwent cranial ultrasonography to
      detect the presence of intracranial hemorrhage. RESULTS: There were 309 women in
      the phenobarbital group and 301 in the placebo group. A total of 247 women (80
      percent) in the phenobarbital group and 235 (78 percent) in the placebo group
      delivered within 24 hours after infusion of the study drug or administration of
      the last maintenance dose. Intracranial hemorrhage or early death occurred in 83
      of the 344 infants born to the women in the phenobarbital group (24 percent) and
      in 74 of the 324 born to the women in the placebo group (23 percent; risk ratio
      for the infants in the phenobarbital group, 1.1; 95 percent confidence interval,
      0.8 to 1.4). Among infants born before 34 weeks' gestation in whom
      ultrasonographic studies were performed, intracranial hemorrhage was diagnosed in
      70 of 311 infants in the phenobarbital group (23 percent) and 64 of 279 in the
      placebo group (23 percent; risk ratio, 1.0; 95 percent confidence interval, 0.8
      to 1.4). CONCLUSIONS: Antenatal administration of phenobarbital does not decrease
      the risk of intracranial hemorrhage or early death in preterm infants.

PMID- 9250850
TI  - Images in clinical medicine. Retropharyngeal abscess.

PMID- 9250851
TI  - Treatment of hepatic encephalopathy.

PMID- 9250852
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 25-1997. A 60-year-old man with pulmonary infiltrates after a
      bone marrow transplantation.

PMID- 9250853
TI  - Use of antimicrobial agents and drug resistance.

PMID- 9250854
TI  - Heparin in acute coronary disease--requiem for a heavyweight?

PMID- 9250855
TI  - Hodgkin's disease--time for a change.

PMID- 9250856
TI  - Mutation watch: PEX PLUS? Gene(s) for X-linked hypophosphatemia and deafness.

PMID- 9250858
TI  - Mapping of rat chromosome 5 markers generated from chromosome-sorted DNA.
AB  - Nineteen markers for rat Chromosome 5 (Chr) were generated by screening
      chromosome-sorted DNA libraries and were subsequently mapped by linkage to known
      markers by use of five F2 rat populations. Along with existing markers, these
      newly produced markers are potentially useful for fine mapping of certain
      quantitative trait loci for blood pressure and for obesity.

PMID- 9250857
TI  - Sucrose consumption in mice: major influence of two genetic loci affecting
      peripheral sensory responses.
AB  - Individual variability in sucrose consumption is prominent in humans and other
      species. To investigate the genetic contribution to this complex behavior, we
      conducted behavioral, electrophysiological, and genetic studies, using male
      progeny of two inbred mouse strains (C57BL/6ByJ [B6] and 129/J [129]) and their
      F2 hybrids. Two loci on Chromosome (Chr) 4 were responsible for over 50% of the
      genetic variability in sucrose intake. These loci apparently modulated intake by
      altering peripheral neural responses to sucrose. One locus affected the response
      threshold, whereas the other affected the response magnitude. These findings
      suggest that the majority of difference in sucrose intake between male B6 and 129
      mice is due to polymorphisms of two genes that influence receptor or peripheral
      nervous system activity.

PMID- 9250860
TI  - Linkage assignment of eleven genes to the porcine genome.
AB  - We report comparative linkage mapping of eleven genes in the swine genome by RFLP
      analysis. These genes include: Acid phosphatase type 5 (ACP5), Cholecystokinin
      Type B Receptor (CCKBR), Antibiotic Peptide (FALL39), Insulin-like Growth Factor
      1 Receptor (IGF1R), Integrin Alpha M (ITGAM), Integrin Beta 2 (ITGbeta2), Opioid
      Receptor Mu-1 (OPRM1), Pro-hormone Converter (PC1/3), Retinol Binding Protein 3
      (RBP3), Ribosomal DNA (RNR1), and Zona Pellucida Glycoprotein 1 (ZP1). The CCKBR
      and ITGbeta2 loci define the ends of the linkage groups on Chromosomes (Chro)
      (SSC) 9p and 13qter, respectively.

PMID- 9250859
TI  - Identification of a leader exon and a core promoter for the rat tuberous
      sclerosis 2 (Tsc2) gene and structural comparison with the human homolog.
AB  - Hereditary renal carcinoma in the Eker rat is an excellent example of
      predisposition to a specific cancer being transmitted as a dominant trait.
      Recently, we identified a germline mutation of the tuberous sclerosis 2 (Tsc2)
      gene in the Eker rat. In the present study, we analyzed the upstream region of
      the Tsc2 gene. A novel leader exon (exon 1a) in a CpG island was found, and core
      promoter activity was identified in a 242-bp region of this island. Exon 1a and
      the promoter region were conserved in the human TSC2 gene. In addition, a rat
      homolog of a gene found upstream of TSC2 in human has been identified, indicating
      that the genomic organization around Tsc2/TSC2 is conserved between the two
      species. Characterization of the 5' region of Tsc2 and TSC2 will facilitate
      studies of the regulation of the gene and its disregulation in tumorigenesis.

PMID- 9250861
TI  - Genetic variation in the porcine myogenin gene locus.
AB  - The myogenin (MYOG) gene fulfills a key function in muscle differentiation by
      controlling the onset of myoblast fusion and the establishment of myofibers. In
      meat-producing animals like pigs and cattle, myofiber numbers have been related
      to growth capacity. We have characterized the porcine MYOG gene to detect genetic
      variation at this locus and to relate it to growth characteristics. MYOG gene
      fragments were isolated by PCR on genomic DNA and by screening a genomic library
      with a mixture of the four human MyoD cDNA fragments. Both the exons and promoter
      region were very similar to the human and mouse genes. Southern blot analysis of
      105 unrelated pigs revealed three polymorphic MspI sites, located in the promoter
      region, the second intron, and at the 3' side of the gene. PCR-RFLP tests
      detecting four MYOG alleles were developed. PCR analysis of a panel of pig-rodent
      somatic cell hybrids confirmed the genetic localization of MYOG on pig Chromosome
      (Chr) 9. The PCR-RFLP tests and microsatellite markers on Chr 9 offer the
      possibility to genotype large numbers of pigs for studies of genetic linkage to
      meat deposition and growth characteristics.

PMID- 9250862
TI  - FISH mapping of the IGF2 gene in horse and donkey-detection of homoeology with
      HSA11.
AB  - Three genomic subclones derived from a phage clone containing the equine IGF2
      gene were used to FISH map the gene on horse (ECA) and donkey (EAS) metaphase
      chromosomes. The gene mapped on ECA 12q13 band and is the first locus mapped to
      this horse chromosome. In donkey the gene mapped very terminal on the long arm of
      one small submetacentric chromosome that shows almost identical DAPI-banding
      pattern with ECA12. This is the first locus mapped in donkey genome. Cross
      species chromosome painting of equine metaphase chromosomes with human Chromosome
      (Chr) 11-specific probe showed homoeology of this human chromosome with ECA12 and
      ECA7. The novel ECA12 comparative painting results are thus in accordance with
      the localization of the equine IGF2 gene. Comparison of the hitherto known
      physical locations of IGF2 in different species, viz. human, cattle, sheep,
      horse, and donkey, shows that this gene tends to maintain a terminal location on
      the chromosome arm.

PMID- 9250864
TI  - Chromosomal mapping and developmental study of Tattered-Hokkaido (Tdho).
AB  - We found a new X-linked dominant mouse mutation. This mouse has the same
      phenotype as Td, which exhibits hyperkeratotic skin, reduced viability in
      affected females, a tendency to be smaller, lighter weight than the normal sibs
      during weaning age, and prenatal lethality in affected males. To map the locus,
      we tested 267 progeny from an intraspecific backcross between affected females
      and wild-origin strain males. Polymerase chain reaction (PCR) was performed with
      microsatellite markers of the proximal region of the mouse X Chromosome (Chr).
      This mutant showed no recombination with DXMit 123, DXMit 55, or DXMit 26. The
      gene position and phenotype of this mutant were very similar to those of Td.
      Therefore, it is speculated that the new mutant gene is a multiple allele of Td,
      and we designated it Tattered-Hokkaido (Tdho). Linkage analysis of these animals
      suggested a possible gene order of cen-(Tdho, DXMit123, DXMit55, DXMit26)
      DXMit161-DXMit54-DXMit103-DXMit52 -DXMit190-DXMit138) in the X Chr. Prenatal
      lethality of male mutants was also investigated, with 12.5 to 16.5 embryonic day
      (E) backcrossed embryos from affected F1 females. It was found that the male
      mutants died between E12.5 and E14.5. The cause of death of male mutants is
      discussed in relation with the other proximal genes of the X Chr.

PMID- 9250863
TI  - Mapping of bovine FcgammaR (FCGR) genes by sperm typing allows extended use of
      human map information.
AB  - Polymorphic sites within the bovine FcgammaRI (FCGR1), FcgammaRII (FCGR2), and
      FcgammaRIII (FCGR3) genes were used for proximal mapping of these genes to bovine
      Chromosome (Chr) 3 (BTA3) with paternal half-sib families from Norwegian Cattle.
      A fine-structure genetic map of the region was obtained by the analysis of 288
      sperm cells from three bulls that were heterozygous for the loci included in the
      study. No recombinants were observed between FCGR2 and FCGR3 (242 sperm cells).
      Considering FCGR2 and FCGR3 as a single locus, a three-point linkage analysis for
      [FCGR2/FCGR3], FCGR1, and INRA003 was carried out. The best-supported order of
      the loci was found to be INRA003-FCGR1-[FCGR2/FCGR3]. Map distances in a two
      point linkage analysis were 10.3 cM between [FCGR2/FCGR3] and FCGR1, and 25.5 cM
      between FCGR1 and INRA003, respectively. This linkage mapping of the bovine FCGR
      gene family resembles the human situation where all FCGR genes are located at Chr
      1 (HSA1), at position q21-q24. Moreover, the results locate the evolutionary
      breakpoint between HSA1q and BTA3 within the human 1q24 region.

PMID- 9250865
TI  - The costimulatory genes Cd80 and Cd86 are linked on mouse chromosome 16 and human
      chromosome 3.

PMID- 9250866
TI  - The open brain (opb) mutation maps to mouse chromosome 1.

PMID- 9250867
TI  - Localization of the rat genes encoding glucagon, glucagon receptor, and insulin
      receptor, candidates for diabetes mellitus susceptibility loci.

PMID- 9250868
TI  - Comparison of genetic variability at microsatellite loci in wild rats and inbred
      rat strains (Rattus norvegicus).

PMID- 9250870
TI  - Mapping genes to swine X chromosome provides reference loci for comparative
      mapping.

PMID- 9250871
TI  - Interleukin-1beta-converting enzyme (ICE) and related cell death genes ICErel-II
      and ICErel-III map to the same PAC clone at band 11q22.2-22.3.

PMID- 9250872
TI  - Partial conservation of the mammalian NRAMP1 syntenic group on chicken chromosome
      7.

PMID- 9250869
TI  - The cytogenetic map of the domestic pig.

PMID- 9250874
TI  - The gene encoding I-mf (Mdfi) maps to human chromosome 6p21 and mouse chromosome
      17.

PMID- 9250873
TI  - Mouse fgf9 (fibroblast growth factor 9) is localized on chromosome 14.

PMID- 9250875
TI  - The gene encoding beta-galactoside alpha2,6-sialyltransferase maps to mouse
      chromosome 16.

PMID- 9250876
TI  - Localization of the mouse glucocorticoid receptor-interacting protein 1 gene
      (Grip1) to proximal chromosome 1 by linkage analysis.

PMID- 9250877
TI  - Genetic mapping of lysyl oxidase-2 (Loxl) on mouse chromosome 9.

PMID- 9250878
TI  - A DEAD-family protein gene, Ddx4, encoding a murine homolog of Drosophila vasa
      maps to the distal end of mouse chromosome 13.

PMID- 9250879
TI  - The mouse urate oxidase gene, Uox, maps to distal chromosome 3.

PMID- 9250880
TI  - Genetic mapping of the C-type natriuretic peptide receptor (Npr2) gene to mouse
      chromosome 4.

PMID- 9250881
TI  - Linkage mapping of the mixed-lineage leukemia (Mll) gene to rat chromosome 8.

PMID- 9250882
TI  - Assignment of porcine ceruloplasmin and v-RAF1 murine viral oncogene homolog 1 to
      chromosome 13 by linkage analysis.

PMID- 9250883
TI  - Assignment of the gene for outer dense fiber of sperm tails (ODF) to porcine
      chromosome 4p11-p14.

PMID- 9250884
TI  - The dilemma of exposing or burying a complementary medical approach.

PMID- 9250885
TI  - Ozone as a bioregulator. Pharmacology and toxicology of ozonetherapy today.
AB  - The disinfectant activity of ozone is well recognized and ozone is used worldwide
      for sterilization of water. The use of ozone as a complementary medical approach
      is less known, because it has mostly been used in an empirical fashion without a
      rational basis and appropriate controls. In spite of this drawback, the use of
      judicious and standardized ozone dosages can elicit the formation of ROS acting
      as natural physiological activators of several biological functions. There is now
      a reasonable understanding of a few mechanisms of action and, using classical
      pharmacological concepts, it appears possible to formulate a rationale for
      optimizing clinical applications. A further exciting development is that ozone,
      being an oxidizer, can upregulate the intracellular anti-oxidant enzymes
      eventually inhibiting the constant, life-long oxidative stress responsible for
      degenerative diseases and aging. Among various routes for the administration of
      ozone, the autohemotransfusion procedure, consisting in exposing blood to ozone,
      i.e. to a calculated and brief oxidative stress, appears safe, simple,
      inexpensive and amenable to be adjusted to different pathological states It is
      hoped that this review will help to dispel prejudices, to clarify that ozone
      toxicity can be tamed, to show that ozone can act as a bioregulator and to
      encourage controlled clinical investigations to evaluate definitely the validity
      of ozonetherapy.

PMID- 9250887
TI  - Clinical significance of erythrosedimentation rate in cancer in relation to
      cytokine production: correlation with high IL-6 and low IL-2 blood
      concentrations.
AB  - Despite its well documented unfavourable prognostic significance in several human
      diseases, including cancer, the cytokinic mechanisms responsible for an increased
      erythrosedimentation rate (ESR) still remain to be better analyzed and defined.
      The recent possibility to measure cytokine concentrations in the blood of
      patients has allowed us to explore the possible relation between ESR values and
      endogenous cytokine secretions. This preliminary study was performed to evaluate
      the relationship between ESR values and serum levels of IL-2 and IL-6, which
      represent the most important cytokines responsible for the activation and the
      suppression, respectively, of host anticancer immune reaction. The study included
      33 consecutive solid tumor patients, 22 of whom showed distant organ metastases.
      Abnormally high values of ESR were present in 21 patients, including 18/22
      metastatic patients and 3/11 nonmetastatic patients. Patients with elevated
      values of ESR showed significantly higher mean levels of IL-6 and significantly
      lower mean concentrations of IL-2 with respect to those found in patients with
      normal ESR values. These results would show that cancer-related increase in ESR
      values is associated with low levels of IL-2 and high levels of IL-6. Since IL-2
      plays an essential role in the anticancer immunity and IL-6 may suppress the
      antitumor immune defenses, the evidence of low levels of IL-2 and high values of
      IL-6 in cancer patients with increased ESR values would explain the unfavourable
      prognostic significance of high ESR values in human neoplasms.

PMID- 9250886
TI  - Differential effect of alpha-tocopherol and ascorbate on oxidative injury induced
      in immune cells by thermal stress.
AB  - As immune cells are often subjected to hyperthermia that can easily occur either
      after intense and/or prolonged exercise or during defense against pathogens, in
      this paper we analysed whether superoxide anion production occurred in
      lymphocytes exposed to high temperature and, consequently, if antioxidants could
      exert any protective function. The results demonstrated that an increase of
      superoxide anion was induced in rabbit lymphocytes exposed to 42 degrees C for
      1h, although cell viability was no affected. However, suppression of either
      Pokeweed mitogen (PWM)-driven cell proliferation, or immunoglobulin production or
      IL-2 synthesis was observed. To evaluate the capacity of antioxidants to restore
      the immune suppressed responses, two vitamins, alpha-tocopherol and ascorbic
      acid, were added to PWM-stimulated cultures following heat treatment. The data
      demonstrated that alpha-tocopherol was able to totally abrogate the inhibitory
      effects mediated by thermal stress, while ascorbic acid did not give any
      protective results.

PMID- 9250888
TI  - Enhancement by monochloramine of the development of gastric cancers in rats: a
      possible mechanism of Helicobacter pylori-associated gastric carcinogenesis.
AB  - The effects of cytotoxic monochloramine on the development of gastric cancers
      induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats.
      After oral administration of drinking water containing the carcinogen and regular
      chow pellets for 25 weeks, rats received regular chow pellets or chow pellets
      containing 20% ammonium acetate, and normal tap water or water containing 30 mM
      sodium hypochlorite, with or without s.c. injection of taurine, until the end of
      the experiment in week 52. Treatment with both ammonium acetate and sodium
      hypochlorite significantly increased the incidence of gastric cancers in week 52,
      while the concomitant use of taurine with ammonium acetate and sodium
      hypochlorite significantly attenuated the enhanced gastric carcinogenesis.
      Spectrophotometric examinations revealed that taurine scavenged monochloramine.
      These findings suggest that Helicobacter pylori-associated gastric carcinogenesis
      may be mediated by monochloramine.

PMID- 9250889
TI  - Role of L-arginine, a substrate for nitric oxide-synthase, in gastroprotection
      and ulcer healing.
AB  - Nitric oxide (NO) synthesized from L-arginine interacts with prostaglandins (PG)
      and sensory neuropeptides in the regulation of mucosal integrity, but the role of
      L-arginine, a substrate for NO-synthase, in gastroprotection and healing of
      chronic gastric ulcers has been little studied. In this study we compared the
      effects of intragastric (i.g.) and systemic (i.v.) administration of L-arginine
      or D-arginine on gastric secretion and acute gastric lesions provoked in rats by
      i.g. application of 100% ethanol, acidified aspirin (ASA), or the exposure to
      3.5h of water immersion and restraint stress (WRS). In addition, the effects of L
      arginine on ulcer healing and the formation of new vessels (angiogenesis) were
      determined, using monoclonal antibody (MAb E-9). L-arginine (10-200 mg/kg i.g.)
      failed to significantly affect gastric secretion but dose-dependently reduced the
      gastric lesions induced by 100% ethanol. ASA, and WRS, the doses inhibiting 50%
      of these lesions being 65, 94, and 72 mg/kg, respectively. This protection was
      accompanied by a significant rise in the gastric blood flow (GBF), whereas L
      arginine given i.v. failed to affect the ethanol-lesions and the GBF. D-arginine
      or the NO-related amino acids--L-glutamine, L-citrulline, or L-ornithine--failed
      to significantly influence these lesions. Suppression of the generation of
      mucosal PG by indomethacin or capsaicin-denervation attenuated the protection and
      hyperemia induced by L-arginine. The inhibition of constitutive NO synthase by L
      NNA had no significant effect on the protection afforded by L-arginine, but
      reduced the gastric hyperemia accompanying this protection. L-arginine (150 mg/kg
      per day, i.g.) accelerated the ulcer healing and increased GBF at the ulcer
      margin, and angiogenesis, whereas treatment with L-NNA had an opposite effect. L
      arginine added to NG-nitro-L-arginine (L-NNA) restored the ulcer healing,
      hyperemia, and angiogenesis. We conclude that: (1) the protective activity of L
      arginine involves gastric hyperemia mediated by NO and a mild irritant effect due
      to enhanced generation of endogenous PG, and (2) the ulcer healing properties of
      L-arginine depend upon its hyperemic and angiogenic actions, possibly involving
      NO.

PMID- 9250890
TI  - Small bowel transit time and colonic fermentation in young and elderly women.
AB  - Small bowel transit time (SBTT) in 15 young and 13 elderly women was assessed by
      measuring breath hydrogen concentrations after they had consumed a solid test
      meal. The meal consisted of 200 g cooked rice, 50 ml miso (made from fermented
      soy bean curd) soup, a boiled egg, and 95.5 g of cooked soy beans with mixed
      vegetables. This meal provided 17 g protein, 14.1 g fat, 92.9 g carbohydrate, 7 g
      dietary fiber, and 565 kcal total energy. The SBTT, calculated by a mean 3 ppm
      increase in breath hydrogen, was 191 +/- 14.9 (mean +/- SE) min in the young and
      188.1 +/- 16.8 min in the elderly group; the difference was not significant.
      Breath hydrogen levels, however, were higher in the young than in the elderly
      group (39.1 +/- 6.3 ppm, vs 22.2 +/- 4.3 ppm, P < 0.05). There was an initial
      peak of hydrogen concentration, reached almost immediately after the ingestion of
      the meal, and then a decline to baseline within 60 min. This initial peak was not
      as pronounced in the elderly subjects. A second peak, indicating the entry of the
      test meal into the cecum, was more pronounced in the young than in the elderly
      group. SBTT did not differ significantly between the two groups, but colonic
      fermentation was more pronounced in the young, both in the fasting and the
      postprandial state.

PMID- 9250891
TI  - Assessment of blood flow in the small intestine by laser Doppler flowmetry:
      comparison of healthy small intestine and small intestine in Crohn's disease.
AB  - Blood flow and blood distribution were investigated in 40 patients with normal
      small intestine and the relation between blood flow and the morphological
      features of Crohn's disease was examined in 11 patients with Crohn's disease by
      laser Doppler flowmetry from the serosal side during surgery. In normal small
      intestine, blood flow was measured at six points: upper, middle, and lower small
      intestine, each of the mesenteric borders, and the antimesenteric surface. In
      Crohn's disease, macroscopically normal tissue and affected lesions were observed
      in detail by intraoperative endoscopy after blood flow measurement. The blood
      flow values in the normal small intestine gradually decreased from the upper to
      the lower small intestine. As the level of inflammation progressed in Crohn's
      disease the blood flow values gradually decreased; the exudative stage of Crohn's
      disease (aphthoid ulcer) showed blood flow values that were slightly below those
      in macroscopically normal tissue. These results are the first to demonstrate
      decreased blood flow in affected lesions in Crohn's disease and changes in blood
      flow according to the degree of inflammation in vivo.

PMID- 9250892
TI  - Mucosal blood flow and generation of superoxide in rat experimental colitis
      induced by succinic acid.
AB  - As we consider succinic acid to be an exacerbating factor in ulcerative colitis,
      we investigated its influence on rat colonic mucosa in terms of mucosal blood
      flow and superoxide generation. We measured mucosal blood flow by the hydrogen
      gas clearance method and superoxide generation by the chemiluminescence method,
      and observed histopathological findings to determine the effects of succinic
      acid. After the instillation of succinic acid of any concentration tested to the
      colon, mucosal blood flow decreased. Histopathologically, the higher the
      concentration of succinic acid, the greater was the erosion formation in the
      colonic mucosa, while significant polymorpho-nuclear cell infiltration superoxide
      generation from colon tissue were observed with 0.01% succinic acid compared with
      higher or lower concentrations. Succinic acid, at fecal concentrations found in
      active stage ulcerative colitis, appears to be implicated in mucosal injury,
      mediated by a decrease in colonic mucosal blood flow and infiltration of
      superoxide-generating polymorpho-nuclear cells into the mucosa.

PMID- 9250893
TI  - Disorder of bile acid metabolism in children with short bowel syndrome.
AB  - The profile of fecal bile acids was examined in 13 children with short bowel
      syndrome; 7 of the 13 did not have diarrhea and the other 6 had intractable
      diarrhea. In children without diarrhea, no severe fat malabsorption was
      recognized, and the content of total bile acids in the feces was within the
      normal range or slightly higher. The ratio of primary to total bile acids showed
      various patterns. In children with intractable diarrhea, in contrast, fat
      malabsorption was observed and the fecal content of total bile acids in these
      patients was more than ten times higher than that of the control group, primary
      bile acids accounting for more than 95% of the total bile acids and taurine- or
      glycine-conjugated bile acids for 10%. In the children with intractable diarrhea,
      the values for the D-xylose absorption test were lower than the normal range.
      These results suggested that, in children with short bowel syndrome with
      diarrhea, the loss of bile acids was strongly associated with a decrease in the
      actual absorptive surface area of the residual small intestine, and the growth of
      the normal bacterial flora was disturbed in the residual intestine. Some children
      with or without diarrhea also had hyper bile acidemia. Ursodeoxycholic acid was
      not effective for the treatment of hyper bile acidemia or fat malabsorption.

PMID- 9250895
TI  - Aneusomy of chromosome 18 is associated with the development of colorectal
      carcinoma.
AB  - Specific loss of heterozygosity of chromosome 18 has been observed frequently in
      advanced colorectal carcinoma and is closely associated with its development. We
      investigated the prevalence of numerical aberrations of chromosome 18 in 44
      specimens of colorectal carcinomas, using fluorescence in situ hybridization. We
      also examined the relationship between aneusomy of chromosome 18 and the
      clinicopathological features of these tumors. Aneusomy of the specimens (monosomy
      and polysomy) was determined when the same aneusomic population was detected in
      more than 15% of the nuclei. The frequency of monosomy and polysomy of chromosome
      18 in colorectal carcinomas was 43% (19/44) and 29% (12/44), respectively. The
      prevalence of monosomy and polysomy 18 was significantly higher in cancers with
      invasion exceeding category T2 compared with T1 (P < 0.01), and with tumor size
      exceeding 20 mm in diameter compared with tumors less than 20 mm (P < 0.05).
      However, the prevalence of aneusomy 18 was not associated with other clinico
      pathological features. The mean survival period and the 5-year survival rate
      after operation in patients with aneusomy 18 was not different from findings for
      those with disomy 18. Our results indicate that aneusomy of chromosome 18 is
      associated with the development of colorectal carcinoma; however, it is not a
      useful indicator of postoperative prognosis.

PMID- 9250894
TI  - Elevated serum concentrations of soluble selectin and immunoglobulin type
      adhesion molecules in patients with inflammatory bowel disease.
AB  - Adhesion molecules mediate the extravasation of leukocytes and their accumulation
      in inflamed tissues. In the present study, serum concentrations of the selectin
      (sP- and sE-selectin) and immunoglobulin supergene family (sICAM-1 and sVCAM-1)
      of adhesion molecules were measured in 93 patients with inflammatory bowel
      disease (Crohn's disease, n = 65; ulcerative colitis, n = 28) and 58 age-matched
      normal controls. sP-selectin serum concentrations (mean +/- SEM ng/ml) of
      patients with Crohn's disease (399 +/- 33 ng/ml) and ulcerative colitis (385 +/-
      42 ng/ml) were increased (P = 0.0067 and P = 0.0193, respectively) compared to
      controls (251 +/- 33 ng/ml). In contrast, E-selectin serum levels of patients
      with Crohn's disease (58 +/- 5 ng/ml) and ulcerative colitis (64 +/- 12 ng/ml)
      were not significantly higher than those of controls (53 +/- 5 ng/ml). sICAM-1
      serum concentrations of patients with Crohn's disease (420 +/- 19 ng/ml) and
      those with ulcerative colitis (375 +/- 40 ng/ml) were elevated (P = 0.0001 and P
      = 0.0473, respectively) compared to controls (297 +/- 8 ng/ml). Further, sVCAM-1
      levels of patients with Crohn's disease (664 +/- 43 ng/ml) and ulcerative colitis
      (963 +/- 162 ng/ml) were increased (P = 0.0222 and P = 0.0121, respectively)
      compared to controls (510 +/- 31 ng/ml). With few exceptions, serum levels of
      soluble adhesion molecules were not significantly correlated to disease activity
      indices or disease localization. Elevated circulating selectin and immunoglobulin
      supergene type adhesion molecules may compete with membrane-bound forms for their
      cognate ligands and thereby limit the rolling and stable adhesion of leukocytes.

PMID- 9250896
TI  - Detection rate of immunochemical fecal occult blood test for colorectal
      adenomatous polyps with severe dysplasia.
AB  - This study was conducted to assess the accuracy of an immunochemical occult blood
      test for detecting colorectal adenomas with severe dysplasia, and to determine
      the relationship between the grading of adenomatous dysplasia and the results of
      this test. Sixteen colorectal adenomas under 1 cm with severe dysplasia, 65
      adenomas under 1 cm with mild-to-moderate dysplasia, 65 adenomas 1 cm or larger
      with mild-to-moderate dysplasia, 65 colorectal cancers and 130 healthy controls
      were investigated. Each subject was tested with an immunochemical fecal occult
      blood test on 3 consecutive days, and the accuracy of the test was evaluated. The
      detection rate of this test was 13% for severe dysplasia under 1 cm, 45% for
      severe dysplasia 1 cm or more, 17% for mild-to-moderate dysplasia under 1 cm, 40%
      for mild-to-moderate dysplasia 1 cm or more, and 89% for colorectal cancers, and
      the false positive rate was 5%, showing a significant difference in the detection
      rate between severe dysplasias 1 cm or more and those under 1 cm (P < 0.05) as
      well as significant difference between severe dysplasias 1 cm or more and mild-to
      moderate dysplasia under 1 cm (P < 0.01), and between cancers and adenomas (P <
      0.001), whereas there was no significant difference between the detection rates
      for severe dysplasia 1 cm or more and mild-to-moderate dysplasia 1 cm or more.
      These results indicate that there is no association between the detection rate of
      this immunochemical occult blood test for adenomas and the grade of adenomatous
      dysplasia.

PMID- 9250897
TI  - Expression of platelet-derived growth factor and its receptor in livers of
      patients with chronic liver disease.
AB  - To find if platelet-derived growth factor contributes to liver fibrosis in
      chronic liver disease, we studied the expression of the B-chain of this cytokine
      and its beta-receptor in livers of patients with chronic hepatitis or cirrhosis.
      Seventeen patients were included in this study. Five specimens of liver tissue
      obtained during autopsy from subjects without liver disease were used as
      controls. The location of the peptides was identified by an immunohistochemical
      technique with monoclonal antibodies. Expression of mRNA for the B-chain was
      assessed by in situ hybridization. Cells stained for the B-chain and expressing
      its mRNA were identified as macrophages. In control tissues, only a few cells
      were stained. In the patients' specimens, most stained cells were in portal areas
      and their number increased with histologic liver damage. In intralobular areas,
      the stained cells were seen in regions of focal necrosis. Portal mesenchymal and
      perisinusoidal cells expressed beta-receptor. These cells were dense in
      periportal areas, where many myofibroblast-like cells were seen. These findings
      suggest that the B-chain of platelet-derived growth factor is released mainly by
      macrophages involved in inflammatory reactions. This cytokine probably acts on
      myofibroblast-like mesenchymal cells, and may be implicated in liver fibrosis in
      chronic liver disease.

PMID- 9250898
TI  - Sex difference in serum 7 alpha-hydroxycholesterol levels in the rat reflect
      hepatic activity of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase and
      cholesterol 7 alpha-hydroxylase.
AB  - Factors that affect serum levels of 7 alpha-hydroxycholesterol were studied in
      the rat. Serum levels of 7 alpha-hydroxycholesterol differed in male and female
      rats fed regular chow (male; 0.2 +/- 0.1 nmol/ml (mean +/- SD); n = 8; female;
      0.4 +/- 0.1 nmol/ml; n = 8). When rats were fed with chow to which 3%
      cholestyramine had been added, the level increased significantly, particularly in
      female rats (male; 0.6 +/- 0.3 nmol/ml; n = 8; female; 2.4 +/- 1.5 nmol/ml; n =
      8). The liver activity of cholesterol 7 alpha-hydroxylase, the rate-limiting
      enzyme for degradation of cholesterol, did not show any sex differences,
      irrespective of whether the animals were fed with regular chow (male; 51 +/- 15
      pmol/min per mg protein; n = 8; female; 58 +/- 21 pmol/min per mg protein; n =
      8), or the cholestyramine-supplemented chow (male; 162 +/- 33 pmol/min per mg
      protein; n = 8; female; 172 +/- 33 pmol/min per mg protein; n = 8). In contrast,
      the activity of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, which acts
      after cholesterol 7 alpha-hydroxylase in the catabolism of cholesterol, showed a
      marked difference between the sexes. In both sexes this enzyme activity was
      higher in cholestyramine-treated rats (male; 963 +/- 78 pmol/min per mg protein;
      n = 8; female; 708 +/- 106 pmol/min per mg protein, n = 8) compared to that in
      that rats received regular chow (male; 622 +/- 83 pmol/min per mg protein; n = 8;
      female; 469 +/- 41 pmol/min per mg protein; n = 8). If the serum level of 7 alpha
      hydroxycholesterol depended solely on the enzyme activity of cholesterol 7 alpha
      hydroxylase, it would be difficult to explain these sex differences, since there
      were no sex differences in levels of cholesterol 7 alpha-hydroxylase. These
      results clearly indicate that, in the rat, the serum level of 7 alpha
      hydroxycholesterol depends not only on cholesterol 7 alpha-hydroxylase activity
      but also on 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase activity.

PMID- 9250899
TI  - Usefulness of ED036 kit for measuring serum PIVKA-II levels in small
      hepatocellular carcinoma.
AB  - As a tumor marker for hepatocellular carcinoma (HCC), serum protein induced by
      vitamin K absence or antagonist-II (PIVKA-II) has high specificity, yet its
      sensitivity is relatively low, marking it less suitable to serve as an adjunct in
      the diagnosis of small HCC. Recently, the ED036 kit (Eisai, Tokyo, Japan), whose
      detection limit is approximately ten times superior to that of a conventional kit
      (Eitest MONOP II, Eisai) has been developed. In this study, serum PIVKA-II levels
      in serum samples from 83 patients with benign chronic liver diseases (CLD) and
      129 patients with HCC were measured with those two kits. With the ED036 kit, the
      cut-off value was set at 40 mAU/ml. For PIVKA-II measured with the ED036 kit,
      sensitivity was 45.0%, specificity 92.8%, and accuracy 63.7%, when we
      discriminated patients with HCC from those with CLD without HCC. While
      maintaining a high specificity, of 92.8%, the ED036 kit showed a significantly
      higher sensitivity than the conventional kit (45.0% versus 27.9%; P < 0.0001).
      With patients who had HCC consisting of a single nodule 30 mm or less in
      diameter, the positivity rate for serum PIVKA-II with the ED036 kit was
      significantly greater than the rate with the conventional kit (21.4% versus 9.5%;
      P < 0.005). Thus, the ED036 kit was thought to be more useful than the
      conventional kit as a tumor marker for small HCC.

PMID- 9250901
TI  - Impaired response of gastric vessels to prostaglandin E2 in rats with persistent
      obstructive jaundice.
AB  - We investigated the response of gastric vessels to prostaglandin (PG) E2 after
      intra-duodenal release of bile in rats with obstructive jaundice. The animals
      were divided in four groups according to duration of bile duct obstruction (BDO):
      control and 1 week (W), 2W, and 3W groups. Prolonged BDO decreased gastric
      mucosal blood flow (BF) significantly. The BF recovered after the release of BDO
      in the 1W and 2W groups, but not in the 3W group. BDO decreased PGE2 content in
      gastric mucosa in the 1W, 2W, and 3W groups. PGE2 decreased vascular perfusion
      pressure of the isolated stomach in the control and 2W groups, but not in the 3W
      group. The response of gastric vessels to PGE2 was poor in the 3W group compared
      with the control and 2W groups. Decreased PGE2 in the gastric mucosa and
      decreased response of gastric vessels to PGE2 may affect gastric blood flow in
      obstructive jaundice.

PMID- 9250900
TI  - Effect of arterial administration of a high molecular weight anti-tumor agent,
      styrene maleic acid neocarzinostatin, for multiple small liver cancer--a pilot
      study.
AB  - To assess the efficacy of the zinostatin derivative, the anti-tumor agent,
      styrene-maleic acid neocarzinostatin, in treating multiple small liver cancers,
      29 patients with multiple hepatocellular carcinoma of 3 cm or less in diameter
      were treated with intraarterial injections of this high molecular weight agent,
      mixed with Lipiodol. Computed tomography 3 months after the first therapy showed
      complete deposition of Lipiodol in the entire area of the original tumor in 8
      patients (27.6%), 50%-99% deposition in 4 (13.8%), 10%-49% in 10 (34.5%), and
      less than 10% in 7 (24.1%). After repeated injections, Lipiodol deposition in the
      entire area of the original tumor was found in 11 patients (37.9%). The degree of
      Lipiodol deposition depended on the angiographic vascularity of the tumor and on
      the images of the computed tomogram during arterial portography. Although
      complete deposition of Lipiodol was found in all tumors in 10 (58.8%) of the 17
      patients with well demarcated round hypervascularity, only 1 (8.3%) of 12
      patients with ill demarcated tumors showed complete deposition of Lipiodol in the
      tumors. Taking into account that hypervascularity on angiograms was closely
      correlated with the degree of Lipiodol accumulation on computed tomograms taken
      later, it appears that well demarcated round-shaped liver cancer is the best
      candidate for styrene-maleic acid neocarzinostatin therapy.

PMID- 9250902
TI  - A rare case of gastric cancer in an acromegalic patient.
AB  - Although it has been demonstrated that acromegalic patients have an increased
      risk of neoplasms, especially colon neoplasms, gastric cancer with acromegaly is
      very rare--only five cases have been reported to date in Japan. We report here a
      rare case of gastric cancer with acromegaly in a 58-year-old woman, whose
      acromegalic change began at age 44. This patient showed typical clinical features
      of acromegaly, with increased concentrations of blood growth hormone (GH) and
      insulin-like growth factor I (IGF-I); she had four types of neoplasms; gastric
      cancer, colon tubular adenoma with moderate atypia, pancreatic mucinous
      cystadenoma, and subcutaneous lipoma. The gastric cancer was macroscopically 0
      IIc type, 3.0 x 2.5 cm in size, and histologically diagnosed as a poorly
      differentiated adenocarcinoma with limited invasion of the mucosal layer. The
      previously documented stimulatory effects of GH and/or IGF-I on tumorigenesis and
      cell proliferation may have been responsible for the development of the multiple
      neoplasms in our patient.

PMID- 9250903
TI  - Malignant lymphoma of the stomach after chemotherapy for hepatocellular
      carcinoma.
AB  - A rare case of malignant lymphoma of the stomach after treatment for
      hepatocellular carcinoma (HCC) is reported. A 72-year old man presented with a
      large mass on the right hypochondrium, which was diagnosed as HCC associated with
      chronic hepatitis C with cirrhosis. The inoperable tumor was treated
      conservatively with cisplatin, etoposide, carboplatin, and Lipiodol infused into
      the hepatic artery, together with transcatheter arterial embolization. The
      patient presented 38 months later with features suggestive of gastric ulceration.
      Endoscopy and histological examination of biopsy material confirmed the presence
      of malignant lymphoma of the stomach. He ultimately died as a result of hepatic
      failure. The clinical presentation suggests that gastric lymphoma was possibly
      related to the lymphotropic effect of hepatitis C virus (HCV) and exacerbated by
      intraarterial injection of the cytotoxic drugs.

PMID- 9250904
TI  - Progressive systemic sclerosis associated with primary small cell carcinoma of
      the stomach.
AB  - A 64-year-old man with a 5-year history of progressive systemic sclerosis (PSS)
      was hospitalized because of melena. Radiological and endoscopic examinations
      showed an ulcerative lesion with sharply demarcated and raised margins in the
      fornix of the stomach. Tumor markers--serum carcinoembryonic antigen (CEA, 11.3
      mg/ml) and neuron-specific enolase (NSE, 38.9 ng/ml) were elevated. Histological
      examination of endoscopic biopsy specimens (and of necropsy specimens) showed
      proliferation of atypical small round cells. Immunohistological examination of
      these cells showed they were positive for epithelial membranous antigen (EMA),
      and neuron-specific enolase (NSE), but negative for UCHL1, leukocyte common
      antigen (LCA), anti-leukocyte B-cell (MB1), and anti-leukocyte T-cell (MT1)
      antigens. Based on these histological and immunohistological tests, a definite
      diagnosis of small cell carcinoma of the stomach with PSS was established. Our
      case is a rare combination of PSS and gastric small cell carcinoma. We also
      reviewed the literature for the association between PSS and gastric cancer in
      Japanese patients.

PMID- 9250905
TI  - Regression of atypical lymphoid hyperplasia after eradication of Helicobacter
      pylori.
AB  - A rare case of endoscopic and histological regression of a gastric lymphoid
      mucosal lesion after eradication of Helicobacter pylori is reported. A 72-year
      old man was suspected of having a low-grade B-cell gastric mucosa-associated
      lymphoid tissue (MALT) lymphoma by endoscopic and histological findings.
      Histology of biopsy specimens showed massive infiltration of atypical lymphocytes
      and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light
      chain expression in the infiltrated atypical lymphocytes to be twofold that of
      lambda light chain. The above diagnosis was thus highly suspected but not
      confirmed. Antibiotic therapy was given on the basis of evidence of H. pylori
      infection. Successful eradication of H. pylori resulted in remarkable improvement
      of endoscopic and histological findings. Follow-up studies were carried out 8
      months after eradication, with no evidence of relapse. The eradication of H.
      pylori appears to be an effective alternative therapy for B-cell
      lymphoproliferative disease, although longer follow-up and further studies are
      needed before this treatment can be established.

PMID- 9250906
TI  - Multiple ulcers of the ileum due to Cytomegalovirus infection in a patient who
      showed no evidence of an immunocompromised state.
AB  - 68-year-old woman presented with abdominal pain and vomiting. After initial
      conservative therapy, laparotomy showed multiple ulcers of the ileum, one of
      which had perforated and adhered to the uterus. The affected segment of the ileum
      was resected. Numerous cytomegalic cells, corresponding to endothelia and
      macrophages, with intranuclear inclusion bodies, were found in microscopic
      sections of the ulcerated lesions. These findings were consistent with
      cytomegalic vasculitis and enteritis. Cytomegalovirus infections of the
      alimentary tract have been reported mainly in severely immunocompromised patients
      or those with predisposing disorders such as ulcerative colitis; their prognosis
      is usually poor. In our patient, there was no obvious immunocompromised state or
      other gastrointestinal disorders. The postoperative course has been uneventful
      for 2 years after surgery. The prognosis of Cytomegalovirus-associated lesions in
      the alimentary tract may be quite good in the immunocompetent patient.

PMID- 9250907
TI  - Varioliform mucosal polypoid lesions in intestinal tract in a patient with adult
      T-cell leukemia.
AB  - We describe a case of adult T-cell leukemia (ATL) with intestinal infiltration.
      In the early clinical stage, the endoscopic findings for the intestine were
      similar to those of amebic enterocolitis, i.e., varioliform mucosal polypoid
      lesions, and amebic cyst was detected with stool examination. Although no
      specific pathological factor could be identified on biopsy, the patient was
      treated for amebiasis as a diagnostic therapy. The findings of varioliform
      mucosal polypoid lesions were detected in the duodenum on endoscopic examination,
      but the lesions eventually disappeared during the treatment for amebiasis. We
      then suspected lymphoma partially masked by the amebiasis. Immunological staining
      of a specimen of the colonic mucosa revealed T cell invasion and Southern
      blotting demonstrated adult T-cell leukemia provirus invasion. Thus, ATL cell
      infiltration of the intestinal tract was confirmed. It is suggested that systemic
      disease should also be considered when varioliform mucosal polypoid lesions are
      found on colonoscopic examination.

PMID- 9250908
TI  - Adenoma of the common human bile duct in Gardner's syndrome may cause relapsing
      acute pancreatitis.
AB  - Familial adenomatous polyposis of the colon, or Gardner's syndrome, is often
      accompanied by adenomas of the stomach and duodenum. We experienced a rare case
      of Gardner's syndrome, with adenomas of the common bile duct, in a patient who
      presented with relapsing acute pancreatitis. Our findings indicate that adenoma
      in the common bile duct or pancreatic duct should be considered as a possible
      etiology when patients with familial polyposis or Gardner's syndrome present with
      pancreatitis, particularly relapsing acute pancreatitis.

PMID- 9250909
TI  - A small glucagonoma of the pancreas with evident ductular and tubular structures.
AB  - A 54-year-old woman was admitted to our department for assessment of a tumor of
      the pancreas found incidentally on abdominal ultrasonography. Examination
      revealed a hypovascular 1-cm sized tumor in the body of the pancreas. Surgical
      examination revealed that the tumor was solitary and located in the pancreas
      body, with no invasion to the adjacent organs iof lymph node involvement. Distal
      pancreatectomy, preserving the spleen, was performed. Histologically, the tumor
      was a glucagonoma with evident ductular and tubular structures, suggesting that
      its site of origin was ductal epithelia.

PMID- 9250910
TI  - Superficial elevated-type early gallbladder carcinoma treated by laparoscopic
      cholecystectomy.
AB  - A 60-year-old woman was admitted to our department for detailed examination of a
      polypoid lesions of the gallbladder detected at the time of a mass survey by
      ultrasound. Endoscopic ultrasonography (EUS) demonstrated a broad-based mass
      lesion, about 10 mm in size, with an irregular surface, at the peritoneal side of
      the body of the gallbladder. The layer structure of the gallbladder wall had not
      been destroyed by the mass. Computed tomography showed no direct invasion of the
      liver or other evidence of metastasis. Type-IIa (superficial elevated-type) early
      gallbladder cancer was suspected and laparoscopic cholecystectomy was performed.
      Histologically, the tumor proved to be a papillo-tubular adenocarcinoma, 9 x 8 mm
      in size, confined to the mucosa and without lymphatic permeation, vascular
      involvement, perineural invasion, or other signs of metastasis. Laparoscopic
      cholecystectomy for gallbladder cancer can be indicated only when a lesion is a
      pedunculated protruded-type (type-Ip) cancer, or a broad-based cancer 10 mm or
      less in size located on the peritoneal side with no destruction of the layer
      structure of the wall demonstrated by EUS. This strategy is justified only with
      precise evaluation of the lesion by EUS.

PMID- 9250911
TI  - Pathology of acquired immunodeficiency syndrome.

PMID- 9250913
TI  - Molecular epidemiologic analysis of Staphylococcus aureus isolated from clinical
      specimens.
AB  - Nosocomial infections caused by Staphylococcus aureus are clinically serious and
      control of such infections requires strain typing to identify the source of
      contamination. Recently, pulsed-field gel electrophoresis (PFGE) and random
      amplified polymorphic DNA (RAPD) assay have been introduced and have provided a
      high level of strain discrimination of S. aureus isolated from clinical
      specimens. This study was performed to classify 82 strains of S. aureus isolated
      from 4 hospitals in the Kwangju-Chonnam area by PFGE and RAPD assay. Methicillin
      resistant S. aureus (MRSA) was identified by disk diffusion method using the
      oxacillin disk and polymerase chain reaction of mecA gene was done in 69 strains.
      Eight-three strains including S. aureus ATCC 25923 were classified into 10 groups
      by RAPD assay, and into 8 groups by PFGE. Classified groups were not related to
      area or hospital. Classification was not characteristic between MRSA and
      methicillin-susceptible strains. Nosocomial infections due to outbreak were
      suggested because some strains disclosed identical band patterns by PFGE. These
      results indicate that medical personnels and instruments are routes of nosocomial
      infections caused by MRSA. PFGE and RAPD assay are powerful tools for the
      epidemiological study of S. aureus, but PFGE is more effective than RAPD assay.
      RAPD assay needs optimal combination of primers.

PMID- 9250914
TI  - Changes in arterial blood PO2, PCO2, and pH during deep hypothermic circulatory
      arrest in adults.
AB  - Safe limits of time and temperature during sleep hypothermic circulatory arrest
      (DHCA) still remain controversial. Furthermore, continuous changes of PaO2,
      PaCO2, and pH have never been measured during DHCA in humans. Continuous
      intraarterial blood gas (CIABG) monitoring is a new technology allowing us to
      study chronological changes occurring due to metabolism during DHCA. When the
      patients' temperature reached 18 approximately 20 degrees C following
      establishment of cardiopulmonary bypass (CPB), circulatory arrest was initiated.
      After a 20-minute period of DHCA, reperfusion commenced with 18 degree C blood.
      We continuously monitored PaO2, PaCO2, and pH immediately before, during and
      following DHCA. Data was analyzed by Student's t-test. PaO2, PaCO2, and pH of pre
      and 5 minutes post DHCA were not significantly different from each other.
      However, during DHCA, the PaO2 was significantly decreased from 229 +/- 34 to 30
      +/- 23 mmHg at 20-minute intervals. But the PaCO2 increased significantly after
      20 minutes of circulatory arrest from 34 +/- 5 to 42 +/- 6 mmHg. However, the pH
      did not change significantly over the 20-minute period. The PaO2 level after 20
      minutes is much lower than before DHCA, it would be well tolerated in
      normothermic adults. The PO2 level in the brain may be even lower given its high
      metabolic rate. So measuring arterial PO2 continuously during DHCA may provide a
      surrogate method for determining maximum safe time under DHCA for adults.

PMID- 9250912
TI  - The effect of cyclophosphamide on Fas-mediated apoptosis.
AB  - Fas is a cell surface protein that can mediate apoptosis and belongs to the tumor
      necrosis factor (TNF) receptor family. Anti-Fas antibody induces apoptotic cell
      death in sensitive cells. Because many chemotherapeutic drugs are capable of
      initiating pathways leading to apoptosis, we determined the effect of
      cyclophosphamide, one of the most widely used anticancer drugs, on Fas mediated
      apoptosis in human lymphoma cell lines; SKW6.4 and Jurkat. Cell lines were
      cultured for 3 days alone in a medium or with cyclophosphamide (2 micrograms/ml).
      Anti-Fas IgM of various concentrations was added after treatment. Apoptosis was
      measured by electrophoresis of DNA fragmentation and surface expression of Fas
      was measured by flow cytometry. These cell lines were found to express Fas and
      were very sensitive to anti-Fas induced by cyclophosphamide in Jurkat except
      SKW6.4. Cyclophosphamide augumented apoptosis mediated by anti-Fas,
      synergistically. These results suggested that the anti-cancer drug might be
      mediated via the pathway of Fas mediated apoptosis in the lymphoma cell lines.

PMID- 9250915
TI  - Sry gene detection in gonads of intersex patients using FISH.
AB  - A candidate gene for sex determination was localized within a 35 kb region of the
      Y chromosome immediately adjacent to the pseudoautosomal boundary. Here, we
      describe a study of Sry detection in the gonads of intersex patients including 5
      male pseudohermaphrodite (MPH), 4 XX true hermaphrodite (TH) and each 1 mixed
      gonadal dysgenesis (MGD) and XX sex reversal, and in the clitoris of 3 female
      pseudohermaphrodite (FPH) by fluorescent in situ hybridization (FISH). Sry gene
      was observed in all cases of MPH and each case of MGD and sex reversal in
      contrast to bare expression in all cases of FPH and most of TH. To our knowledge,
      the Sry gene itself functions testicular determination in almost all intersex
      cases except true hermaphrodite, a distinguished type of intersex in a different
      pathogenesis. In addition, FISH might be useful to detect the translocated Sry
      gene and localize the signal with ease.

PMID- 9250916
TI  - Inhibition of neointimal proliferation of rat carotid artery by sulodexide.
AB  - Sulodexide, a glycosaminoglycan-containing compound, is known to have an
      antiproliferative effect on vascular smooth-muscle cells, in vitro, as well as
      antithrombotic and fibrinolytic effects. But there are few reports about the
      effect of neointimal proliferation in vivo. In this study, we examined whether
      Sulodexide was effective in the inhibition of neointimal proliferation after
      vascular injury. Ten-week-old Sprague-Dawley rats were subjected to vascular
      injury by endothelial denudation of the common carotid artery by using a balloon
      catheter. They were then allocated randomly into a control group (saline 2 ml for
      3 days, and then 1 ml for 18 days, IM) and a treated group (Sulodexide 10
      mg/kg/day for 3 days, and then 4 mg/kg/day for 18 days, IM). Three weeks after
      vascular injury, we analyzed the neointimal proliferation using morphometry. The
      neointimal proliferation was significantly reduced in the treated group compared
      to the control group (Ratio of neointimal area to medial area; 118.39 +/- 6.80%
      in the treated group, 177.25 +/- 17.25% in the control group). This result showed
      that Sulodexide might be effective in reducing the rate of restenosis after
      balloon angioplasty.

PMID- 9250917
TI  - Transforming growth factor beta 1 expression in gastric carcinoma.
AB  - Many types of human malignant tumor have been reported to amplify transforming
      growth factor-beta 1 (TGF-beta 1) gene and overexpress its protein. However,
      little work has been done about the content of TGF-beta 1 protein in tissue and
      blood of patients with malignant tumors. TGF-beta 1 protein of tissue (n = 29)
      and serum TGF-beta 1 levels in patients with gastric carcinoma (n = 62) were
      compared with those in normal subjects (n = 10) using a TGF-beta 1 enzyme-linked
      immunosorbent assay. Also, expression of TGF-beta 1 mRNA (n = 20) and
      immunohistochemical distribution of the protein (n = 70) in gastric carcinoma
      tissues were studied. The immunohistochemical expression of TGF-beta 1 protein
      was significantly correlated with the tissue TGF-beta 1 content (r = 0.45 : p <
      0.05). The content of TGF-beta 1 was 311 +/- 212 ng/g wet carcinoma tissue. TGF
      beta 1 mRNA was expressed in gastric carcinoma cells. However, unexpectedly serum
      TGF-beta 1 levels in patients with gastric carcinoma were lower (97.1 +/- 29.4
      ng/ml) than those in normal subjects (140.3 +/- 85.7 ng/ml, P < 0.05). Our
      results support that the tumor cells directly produce TGF-beta 1 and that
      semiquantitative immunohistochemical staining method for TGF-beta 1 protein is a
      validative method for TGF-beta 1 protein quantitation.

PMID- 9250918
TI  - Correlation of histopathologic classification with proliferative activity and DNA
      ploidy in 120 intracranial meningiomas, with special reference to atypical
      meningioma.
AB  - Histologic classification of 120 meningiomas was correlated with their
      proliferative fraction and DNA ploidy using immunohistochemistry and flow
      cytometry to differentiate histologically atypical meningiomas from benign ones.
      Histologically, the 120 meningiomas included 101 benign (43 meningotheliomatous,
      40 transitional, 11 fibroblastic, 2 secretory, 2 microcystic, 2 angiomatous, and
      1 psammomatous), 15 atypical, and 4 malignant meningiomas. As a histologic
      spectrum between the benign and malignant meningiomas, atypical meningiomas were
      defined by the presence of two of the following criteria; high cellularity, focal
      necrosis, uninterrupted growth pattern, and certain cytologic findings i.e., high
      nuclear/cytoplasmic ratio, coarse chromatin, and prominent nucleoli. In 56 cases,
      immunostaining for proliferating cell nuclear antigen showed higher proliferating
      cell fraction in atypical and malignant meningiomas than that in benign
      meningiomas (p < 0.05). In the flow cytometric analysis, aneuploidy was more
      often seen in atypical meningiomas compared to benign meningiomas (p < 0.05). We
      found that benign, atypical, and malignant meningiomas could be histologically
      classified and correlated with proliferative activity and DNA ploidy pattern.
      Therefore, atypical meningiomas should be distinguished from benign meningiomas
      by histopathologic examination and confirmed by studies on their proliferation
      fractions and DNA ploidies.

PMID- 9250919
TI  - Expression of alpha-1-antichymotrypsin in prostate carcinoma.
AB  - Prostate specific antigen (PSA) is a glycoprotein with the enzymatic activity of
      serine protease, the gene which is encoded in the human glandular kallikrein gene
      locus. Catalytically active PSA released into serum may be inactivated by a
      complex formation with alpha 1ACT (ACT) and alpha 2MG (MG), two major protease
      inhibitors. The serum complex-to-total PSA ratio can be used as a marker for the
      differentiation between prostate carcinoma (PCa) and a benign lesion because of a
      significant elevation of PSA binding to ACT in PCa. Apparently higher
      immunohistochemical expressions of PSA and ACT have been reported in PCa of low
      Gleason scores when compared with benign lesions. The fact that only normal
      secretory epitheliums are capable of producing ACT was recently proved by
      immunohistochemical and in situ hybridization methods. Our immunohistochemical
      study of ACT showed a tendency toward stronger expression in high Gleason grade
      PCa than in low Gleason grade Pca. Prostate intraepithelial neoplasia (PIN), as
      well as BPH, seldom react to ACT. Expression of ACT in normal ducts or acini was
      influenced by their location. In a normal prostate, expression of ACT was
      predominantly in secretory epithelial cells, with a minority of basal cells and
      rarely in the interdigitating neuroendocrine cells. Whereas the potency of ACT
      production in epithelial cells almost always appeared to be suppressed under
      normal conditions, it was noted that a strong expression of ACT was apparent in
      the normal ducts or acini near a high grade carcinoma with a weak reaction to
      ACT. ACT expression is much more enhanced in high grade carcinomas and in the
      residual normal acini adjacent to carcinomas of low ACT expression, presumably
      representing scale down the elevated PSA.

PMID- 9250920
TI  - Thin glomerular basement membrane disease: light microscopic and electron
      microscopic studies.
AB  - Benign recurrent hematuria usually indicates a good prognosis. This condition is
      associated with abnormally thin glomerular basement membranes. Of 680 renal
      biopsy cases in which lower urinary tract disease had been excluded by careful
      study, 25 cases from seven children and eighteen adults met the criteria for thin
      glomerular basement membrane disease, placing the incidence of the disease at
      3.7%. The mean patient age was 32.4 years and the male to female ratio was 1 to
      5.3. The primary finding was microscopic hematuria in eighteen patients and gross
      hematuria in five patients. Among eighteen patients who had microscopic
      hematuria, one patient also exhibited proteinuria and one patient suffered from
      acute renal failure due to acute drug-induced interstitial nephritis. Proteinuria
      was only found in one patient. All of the patients had normal renal function,
      with the exception of one who suffered from acute renal failure. The duration of
      hematuria from the time of detection to the date of biopsy ranged from 3 months
      to 30 years with a mean interval of 56.6 months. No apparent evidence of familial
      hematuria in any patient was noted. Under light microscopy most glomeruli were
      normal. However, five cases showed focal global sclerosis. Under
      immunofluorescence microscopy seventeen cases were negative for all
      immunoglobulins, for complement, and for fibrinogen. Eight cases showed
      nonspecific mesangial deposition of fibrinogen and/or IgM. Ultrastructurally,
      extensive diffuse thinning of the GBM was a constant finding. The mean thickness
      of the GBM was 203.2 +/- 28.3 nm (n = 25); the thickness in adult (201.4 +/- 27.5
      nm; n = 18) did not differ from that in children (208.1 +/- 32.0 nm; n = 7).

PMID- 9250921
TI  - Laparoscopic mobilization of the inferior epigastric artery for penile
      revascularization in vasculogenic impotence.
AB  - A laparoscopic approach was used for penile revascularization in a patient with
      vasculogenic impotence to avoid the long abdominal incision which was
      traditionally required to harvest the inferior epigastric artery as a neoarterial
      source. Despite the time-consuming nature of laparoscopy, this procedure was as
      efficacious but less morbid and required less convalescence than open
      revascularization. Whether more patients may benefit from this procedure must be
      evaluated in further studies.

PMID- 9250922
TI  - Aspergillus nidulans infection in a patient with chronic granulomatous disease.
AB  - Aspergillus nidulans is one of the several species of Aspergillus with low
      pathogenicity. The significant infections of A. nidulans in human have rarely
      been reported, almost exclusively in patients with chronic granulomatous disease
      (CGD). CGD is a primary immunodeficiency disease which results from the absence
      of the NADPH oxidase in the phagocytic cells, leading to recurrent pyogenic
      infection and granuloma and abscess formation. Here we report a fatal case A.
      nidulans infection in a six-year-old boy with chronic granulomatous disease. A.
      nidulans was isolated from the culture of a paraspinal abscess and Aspergillus
      was detected in the surgical tissue by in situ hybridization. The patient
      succumbed despite prolonged treatment with high-dose amphotericin B, itraconazole
      and interferon-alpha. To our knowledge, this is the first report of A. nidulans
      infection in Korea.

PMID- 9250923
TI  - Acute Myelitis after hepatitis B vaccination.
AB  - We report a case of myelitis after plasma-derived hepatitis B vaccination. The
      patient was a 31-year-old man who presented with progressive sensory symptoms in
      extremities that developed 2 weeks after a third vaccination. MRI of the
      cervicothoracic region revealed swelling and T2 high signal at the level of C4 to
      C5 cord, and isolated enhancement in the posterior columns between C4 and C5
      cord. The significance of MRI findings and HLA haplotype of the patient will be
      briefly discussed.

PMID- 9250924
TI  - Lymphoepithelial carcinoma of the submandibular gland--a case report.
AB  - A case of lymphoepithelial carcinoma occurring in the left submandibular salivary
      gland is presented. Histologic features of this rare malignancy are described in
      detail. This unusual carcinoma has been described frequently in Eskimos and is
      usually located in the parotid gland. The raised serum IgG to Epstein-Barr virus
      capsid antigen suggests a causal relationship between Epstein-Barr virus and this
      type of salivary gland carcinoma.

PMID- 9250925
TI  - Gastric metastasis of mammary signet ring cell carcinoma--a differential
      diagnosis with primary gastric signet ring cell carcinoma.
AB  - Metastasis of breast carcinoma to the stomach is relatively uncommon, although
      metastasis to other organs such as lung, bone, and lymph nodes is not rare. It
      may cause difficulty in differentiating from primary gastric carcinoma. We report
      a case of signet ring cell carcinoma of the breast with metastasis to the stomach
      with illustrations of histologic findings of both lesions. The results of
      immunohistochemical stainining with GCDFP-15 (gross cystic disease fluid protein
      15), that can be used to differentiate primary gastric signet ring cell carcinoma
      and metastatic mammary signet ring cell carcinoma, are described.

PMID- 9250926
TI  - A case of prostate cancer in 34 year old man presenting with generalized
      lymphadenopathy mimicking malignant lymphoma.
AB  - We report a case of prostate cancer in 34 year old man presenting with
      generalized lymphadenopathy mimicking malignant lymphoma without any urinary
      symptoms. Lymph node biopsy revealed metastatic adenocarcinoma and
      immunohistochemical stain was strongly positive to prostate antigen (PSA). Serum
      PSA level was also markedly elevated. Transrectal ultrasonogram showed mild
      enlargement in right lobe of prostate. Needle biopsy finding of prostate also was
      consistent with adenocarcinoma. Bone scan revealed multiple metastatic lesions
      including vertebrae, ribs, pelvis, and both femurs. Generalized lymphadenopathy
      and elevated PSA level was decreased after bilateral orchiectomy.

PMID- 9250927
TI  - Cardiac tamponade during transesophageal echocardiography in the patient of
      circumferential aortic dissection.
AB  - A 43-year-old woman, whose physical findings were consistent with Marfan's
      syndrome, presented with acute chest pain. Transthoracic two-dimensional
      echocardiography demonstrated dilated ascending aorta with a circular shape
      intimal flap at the root level. Subsequently, the patient required
      transesophageal echocardiography (TEE), but during esophageal intubation, the
      patient developed acute pericardial tamponade which resulted in death in spite of
      cardiopulmonary resuscitation. Although, some investigators recommend TEE as the
      first choice of diagnostic method of aortic dissection, hemodynamic stability is
      very important during TEE study. Therefore, aggressive sedation may be required
      in the case of circumferential dissection of the ascending aorta to prevent the
      increases of the blood pressure and the heart rate which suggested an extensive
      tear of the aortic intima during TEE procedure.

PMID- 9250928
TI  - Oral lesions in organ transplant patients.
AB  - Patients who have undergone organ transplantation can present with a variety of
      oral lesions that appear to be related either directly to their medication or
      arise as a consequence of drug-induced immunosuppression. Such lesions include
      hairy leukoplakia, an increased propensity to both fungal and viral infections
      and a high incidence of malignant change, especially lip cancer. Cyclosporin
      remains the immunosuppressant of choice in most transplant patients. Gingival
      overgrowth is the main unwanted oral effect associated with cyclosporin. Some 30%
      of dentate transplant experience this problem, which is further compounded by
      concomitant medication with a calcium channel blocker. This review appraises the
      various oral problems that can arise in this group of patients and emphasises the
      importance of regular oral screening and the establishment of links with the
      various transplant teams.

PMID- 9250929
TI  - Detection of herpes simplex virus type 1 shedding in the oral cavity by
      polymerase chain reaction and enzyme-linked immunosorbent assay at the prodromal
      stage of recrudescent herpes labialis.
AB  - Recrudescent herpes labialis (RHL) is a disease caused by herpes simplex virus
      (HSV), predominantly type 1 (HSV-1). We have monitored HSV-1 shedding in the oral
      cavity by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays
      (ELISA) using digoxigenin-labeled primers designed to amplify a 278 bp segment of
      the HSV-1 UL 42 region. Prodromal RHL was confirmed by thermographic imaging in
      22 patients. Infectious virus was not detected using tissue culture for virus
      isolation (0/22). Using PCR and agarose gel electrophoresis, we could detect HSV
      1 DNA in 8/22 patients. Using a biotinylated-probe internal to the predicted
      sequence of the PCR product, HSV-1 DNA was detected in 10/22 patients by ELISA.
      We conclude that HSV-1 DNA is shed into the oral cavity of patients presenting
      with sub-clinical RHL and that the PCR-ELISA technique represents a more
      sensitive method to monitor HSV-1 shedding than conventional tissue culturing or
      PCR-electrophoresis alone.

PMID- 9250930
TI  - Evaluation of argyrophilic nucleolar organizer regions (AgNORs) in oral
      carcinomas in relation to human papillomavirus infection and cytokinetics.
AB  - The numbers of argyrophilic nucleolar organizer regions (AgNORs) were quantified
      in oral carcinomas (n = 39) with or without human papillomavirus (HPV) infection.
      The AgNOR counts of the HPV-positive samples (7.15 +/- 2.13) were not
      significantly (P = 0.09) higher than those of the HPV-negative ones (6.16 +/-
      1.89). Furthermore, the lesions infected with multiple HPV types had greater
      counts than those with HPV type 16/18 infection alone. Significant differences
      were observed between the mean counts of the poorly (10.50 +/- 0.54), moderately
      (7.31 +/- 1.07) and well- (5.12 +/- 0.85) differentiated carcinomas. The mean
      AgNOR numbers in the oral carcinomas at TNM stages III/IV were found to be
      significantly (P < 0.01) higher than the numbers in corresponding stage II
      lesions. Cytokinetics of the lesions assessed by the bromodeoxyuridine (Brdu)
      labelling index (LI%) showed a linear correlation (r = 0.91; P < 0.0001) with
      their respective mean AgNOR counts.

PMID- 9250931
TI  - p53 gene mutations and HPV infection in primary head and neck squamous cell
      carcinomas do not correlate with overall survival: a long-term follow-up study.
AB  - We analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110
      patients for p53 gene mutations, and 92 of them for human papillomavirus (HPV)
      infection, in order to evaluate the prognostic significance of these factors by
      comparison with clinical follow-up data. Mutations within the exons 5 to 8 of the
      p53 gene were found in 48 tumors (44%). Sequencing revealed in most cases mis
      sense mutations (16/21). Frequency of p53 gene mutations was not related to the
      tumor stage or the presence of lymph node metastases. Of the 46 tumors that were
      analyzed by immunohistochemistry, 26 stained positively (56%). The number of
      positively stained nuclei increased slightly with decreasing differentiation of
      the tumors, whereas no correlation was found between tumor stage and
      immunoreactivity. An infection with the high-risk HPV types 16 and 18 could be
      detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99
      patients within a range of 2 to 112 months. No dependence of overall survival on
      the presence of p53 gene mutations or HPV infection could be observed. The
      absence of statistically significant correlations between p53 gene mutation and
      progressive disease, however, does not deny its putative relevance in early
      phases of tumor development.

PMID- 9250932
TI  - Loss of heterozygosity of APC and MCC genes in oral squamous cell carcinomas in
      Taiwan.
AB  - Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in
      colon cancer (MCC) genes was investigated in 37 untreated human primary oral
      squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was
      observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of
      13 (69.2%) heterozygous patients at MCC> Homozygous deletion of MCC was detected
      in one patient. Of the 37 patients, 29 were informative at APC or MCC or both;
      LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were
      informative for both genes; LOH at both loci was found in only three of these
      cases. LOH at the APC and/or MCC was found in both early and advanced stages of
      oral SCCs. No significant correlation was observed between LOH at the APC and/or
      MCC locus and the patients' tobacco/betel quid consumption, tumour location, TNM
      status, or histological differentiation. These results suggest that LOH at the
      APC and/or MCC may be an early event and may play a role in the pathogenesis of
      human oral SCCs in Taiwan.

PMID- 9250934
TI  - Effect of snuff and smoking on tenascin expression in oral mucosa.
AB  - We have shown, by using two monoclonal antibodies (143DB7 and 100EB2), that the
      expression of the extracellular matrix protein tenascin (Tn) is increased in the
      connective tissue of biopsies taken from snuff users' and tobacco smokers' oral
      mucosa. In normal oral mucosa Tn was seen to underlie the epithelium as a thin
      delicate band. The most increase in Tn reaction was observed in snuff users'
      mucosa while the immunoreaction in smokers' mucosa was less conspicuous. Often
      the most prominent Tn reaction took place in association with round cell
      inflammatory infiltration, indicating epithelial irritation. Tn has been shown to
      take part in epithelial-mesenchymal interactions during embryogenesis, wound
      healing and tumorigenesis. Here, a superficial epithelial irritant has been shown
      to cause conspicuous alterations not only in the epithelial cell layers but also
      in the underlying connective tissue by increasing its Tn content. As a result of
      our findings we suggest a further link for Tn in a dynamic epithelial-mesenchymal
      interplay by virtue of this marked connective tissue reaction in snuff users' and
      smokers' oral mucosa.

PMID- 9250933
TI  - The mitogenic effect of KGF and the expression of its cell surface receptor on
      cultured normal and malignant human oral keratinocytes and on contiguous
      fibroblasts.
AB  - This study examined the mitogenic response to keratinocyte growth factor (KGF) of
      normal and tumour-derived human oral keratinocytes in which the degree of
      cellular differentiation was known and in contiguous fibroblast cultures derived
      from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were
      stimulated by KGF, thereby demonstrating epithelial target cell specificity of
      the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured
      in the absence of the 3T3 fibroblast support broadly correlated with the degree
      of cellular differentiation; well-differentiated keratinocytes were stimulated
      more by KGF than their less differentiated counterparts. Malignant oral
      keratinocytes expressed KGF cell surface receptors (KD 451-709 pM; receptors/cell
      2306-13645), but KGF receptor mRNA did not correlate with either KGF-induced
      mitogenesis or the degree of epithelial cell differentiation. When the tumour
      derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the
      mitogenic response to KGF was comparable to normal epithelial cells. The results
      suggest that KGF-mediated growth stimulation may not be significant in providing
      a selective advantage for the growth of malignant keratinocytes.

PMID- 9250935
TI  - Odontogenic myxoma in an adolescent with tuberous sclerosis.
AB  - Tuberous sclerosis is a hamartoneoplastic syndrome characterised by early onset
      of convulsive seizures with mental retardation. Oral abnormalities, including
      enamel hypoplasia and mucosal fibromas, have been previously reported. We report
      here a 17-year-old girl with this disorder who had received repeated dental
      trauma. She presented with a swelling associated with a traumatised maxillary
      central incisor that suggested a diagnosis other than the odontogenic myxoma
      found at operation. Odontogenic myxoma has not previously been reported in this
      condition; it may represent an unusual phenotypic expression of the genetic
      defect understood to determine tuberous sclerosis, or it may be an unrelated
      coincidental finding.

PMID- 9250936
TI  - Myxoglobulosis in an extravasation mucocele of the lower lip.
AB  - A case of extravasation mucocele showing an unusual intraluminal globular
      organization of the mucous content is described. The cystic lesion was obtained
      from the lower lip of a 10-year-old Japanese girl and presented as a painless
      swelling of 1 year duration. Histologically, the cyst cavity was filled with
      round globules and encapsulated by a granulation tissue wall devoid of a lining
      epithelium. To our knowledge this peculiar histological pattern has not been
      previously described in an oral mucocele. Clinicopathological features of
      'myxoglobulosis of the appendix', a morphological variant of appendiceal
      mucocele, appear to be related to the present case.

PMID- 9250937
TI  - Reflections on the founders and pioneers panel.

PMID- 9250939
TI  - The Minnesota Model.

PMID- 9250938
TI  - Social model of recovery: origin, early features, changes, and future.

PMID- 9250940
TI  - Developmental features of the therapeutic community: imprints--actions and
      discoveries.

PMID- 9250941
TI  - Methadone maintenance treatment: The first thirty years.

PMID- 9250942
TI  - Addiction medicine and the free clinic movement.

PMID- 9250943
TI  - Blending policy and research: the California outcomes study.

PMID- 9250944
TI  - Ketamine psychedelic therapy (KPT): a review of the results of ten years of
      research.
AB  - Ketamine is a prescription drug used for general anesthesia. In subanesthetic
      doses, it induces profound psychedelic experiences and hallucinations. The
      subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in
      the authors' use of ketamine-assisted psychotherapy for alcoholism. The results
      of a controlled clinical trial demonstrated a considerable increase in efficacy
      of the authors' standard alcoholism treatment when supplemented by ketamine
      psychedelic therapy (KPT). Total abstinence for more than one year was observed
      in 73 out of 111 (65.8%) alcoholic patients in the KPT group, compared to 24% (24
      out of 100 patients) of the conventional treatment control group (p < 0.01). The
      authors' studies of the underlying psychological mechanisms of KPT have indicated
      that ketamine-assisted psychedelic therapy of alcoholic patients induces a
      harmonization of the Minnesota Multiphasic Personality Inventory (MMPI)
      personality profile, positive transformation of nonverbalized (mostly
      unconscious) self-concept and emotional attitudes to various aspects of self and
      other people, positive changes in life values and purposes, important insights
      into the meaning of life and an increase in the level of spiritual development.
      Most importantly, these psychological changes were shown to favor a sober
      lifestyle. The data from biochemical investigations showed that pharmacological
      action of KPT affects both monoaminergic and opioidergic neurotransmitter
      metabolism, i.e., those neurochemical systems which are involved in the
      pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis
      demonstrated that ketamine increases theta activity in cerebrocortical regions of
      alcoholic patients. This is evidence of the reinforcement of limbic cortex
      interaction during KPT session.

PMID- 9250945
TI  - Use of drugs among street children in Brazil.
AB  - The purpose of this study has been to assess drug consumption among children in
      five Brazilian state capitals during 1993. The sample was composed of street
      children who were given assistance in institutions, and data was collected by
      means of anonymous individual interviews. Five hundred sixty five boys and girls
      were interviewed: 74.3% reported having used drugs (not including alcohol and
      tobacco) at least once in their life. Solvents, followed by marijuana, were the
      most cited drugs. Important regional differences were observed concerning other
      drugs. Consumption of cocaine, including crack, seems restricted to the southeast
      region, whereas psychotropic medication was consumed more in the northeast of the
      country. Drug initiation among these children seems to be a consequence of street
      life and is part of their group lifestyle.

PMID- 9250946
TI  - Party subculture or dens of doom? An epidemiological study of rave attendance and
      drug use patterns among adolescent students.
AB  - Based on 1853 questionnaires derived from adolescent students participating in
      the 1995 Ontario Student Drug Use Survey, this article describes the prevalence
      of rave attendance and the drug-use profile of rave attendees and those
      participating in similar activities (i.e. bush parties). The results showed that
      13% of the sample attended a rave during the 12 months before the survey.
      Although rates of drug use were higher among rave attendees than nonattendees,
      differences were more related to participation in other recreational activities.
      The drug-use pattern for one-third of rave attendees (those who did not attend
      similar activities, i.e., bush parties) was not dramatically different from those
      who attended bush parties only. However, for two-thirds of rave attendees, drug
      use was significantly elevated. Although rave attendance is not prevalent,
      experienced drug users are attracted to raves, as earlier generations of drug
      users were attracted to rock concerts. Consequently, although the size of this
      population is relatively small, the implementation of harm reduction strategies
      is appropriate.

PMID- 9250947
TI  - The intravenous injection of illicit drugs and needle sharing: an historical
      perspective.
AB  - This study reviewed the literature on the history of needle sharing and
      intravenous drug abuse. Reports suggest that needle sharing was practiced by drug
      abusers as early as 1902 in China and 1914 in the United States. Intravenous drug
      abuse was first mentioned in the literature in 1925. However other references
      suggest that some opioid users were injecting intravenously prior to 1920.
      Outbreaks of malaria in Egypt, the United States, and China between 1929 and 1937
      were attributed to needle sharing and intravenous injection of opioids. These
      reports suggest that both needle sharing and intravenous drug use were common by
      1937. Factors such as medical use of intravenous injections, enactment and
      zealous enforcement of antinarcotic laws, and interactions among drug users in
      institutional settings such as regional hospitals and prisons may have
      contributed to the spread of both needle sharing and the intravenous technique
      among drug abusers.

PMID- 9250949
TI  - Set, setting, and matrix.
AB  - The future use of psychedelics as an aid to therapeutic change is bound to come.
      The best source of information on how to use these extraordinary drugs is clearly
      a detailed description of the successes (and failures) of those researchers who
      have used these compounds to bring curative, creative and growth-potentiating
      experiences to their patients. A study of their work is recommended in order to
      identify those elements that lead to successful sessions. Two known essential
      elements are "set," which involves the personality and experiences of the
      patient, and "setting," which has to do with the environment of the session. A
      third element of importance is that of "matrix," which includes consideration of
      the environment (1) from which an individual comes, (2) in which the individual
      lives during the time of the sessions, and (3) to which the individual returns
      after successful therapy--the everyday living space; these three elements are
      discussed.

PMID- 9250948
TI  - Motivational factors in cocaine pharmacotherapy trials with methadone-maintained
      patients: problems and paradoxes.
AB  - Phamacotherapy trials for cocaine abuse among methadone-maintained patients have
      typically reported negative findings as well as high rates of cocaine use during
      the trial. The contribution of motivational factors to these results is a
      potentially important, under investigated area. This article points out that some
      methadone-maintained patients may enter a trial for cocaine abuse with little
      desire for treatment, motivated primarily to continue receiving methadone or to
      avoid program sanctions for continued cocaine use. Participants in clinical
      trials may constitute a phase delaying discharge in a cyclic pattern of multiple
      treatment episodes. Testing a pharmacologic agent in a motivationally
      inappropriate sample may not provide a good estimate of the agent's
      effectiveness. In view of the important public health role that methadone
      maintenance programs play in preventing HIV transmission, and the subversion of
      this role by intravenous cocaine use, solutions to these problems are urgently
      needed. The authors suggest several possible approaches, including pre- and
      posttreatment motivation assessment, as well as the inclusion of psychosocial
      interventions that provide the context for the emergence of potential medication
      effects.

PMID- 9250961
TI  - Total chemical synthesis of chirally pure (6S)-tetrahydrofolic acid.

PMID- 9250962
TI  - Analysis of folates using combined affinity and ion-pair chromatography.

PMID- 9250963
TI  - Molar quantitation of folates by gas chromatography-mass spectrometry.

PMID- 9250964
TI  - Microbiological assay of folates in 96-well microtiter plates.

PMID- 9250965
TI  - Microbiological assay for serum, plasma, and red cell folate using cryopreserved,
      microtiter plate method.

PMID- 9250966
TI  - Determination of tetrahydrobiopterin biosynthetic activities by high-performance
      liquid chromatography with fluorescence detection.

PMID- 9250967
TI  - Microtiter plate assay for biopterin using cryopreserved Crithidia fasciculata.

PMID- 9250968
TI  - Identification and assay of folate catabolites in human urine.

PMID- 9250969
TI  - Enzymatic determination of folylpolyglutamate pools.

PMID- 9250970
TI  - Synthesis and interconversion of reduced folylpolyglutamates.

PMID- 9250971
TI  - Chemical synthesis of (6S)-5-formyl-5,6,7,8-tetrahydropteroylpoly-gamma-L
      glutamates.

PMID- 9250972
TI  - Biotin derivatives of folate compounds: synthesis and utilization for
      visualization and affinity purification of folate transport proteins.

PMID- 9250973
TI  - Preparation of stable isotopically labeled folates for in vivo investigation of
      folate absorption and metabolism.

PMID- 9250974
TI  - Interconversion of 6- and 7-substituted tetrahydropterins via enzyme-generated 4a
      hydroxytetrahydropterin intermediates.

PMID- 9250975
TI  - Enzymatic synthesis of 6R-[U-14C]tetrahydrobiopterin from [U-14C]GTP.

PMID- 9250976
TI  - Use of 10-formyl-5,8-dideazafolate as substrate for rat 10-formyltetrahydrofolate
      dehydrogenase.

PMID- 9250977
TI  - Human cytosolic folylpoly-gamma-glutamate synthase.

PMID- 9250978
TI  - Folylpolyglutamate synthase from higher plants.

PMID- 9250979
TI  - Purification of folate-dependent enzymes from rabbit liver.

PMID- 9250981
TI  - Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase
      methenyltetrahydrofolate cyclohydrolase.

PMID- 9250980
TI  - Human 5,10-methenyltetrahydrofolate synthetase.

PMID- 9250982
TI  - Monofunctional NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase from
      Saccharomyces cerevisiae.

PMID- 9250983
TI  - Methionine synthase from pig liver.

PMID- 9250984
TI  - Purification and assay of cobalamin-dependent methionine synthase from
      Escherichia coli.

PMID- 9250985
TI  - Formyltetrahydrofolate hydrolase from Escherichia coli.

PMID- 9250986
TI  - Use of 13C nuclear magnetic resonance to evaluate metabolic flux through folate
      one-carbon pools in Saccharomyces cerevisiae.

PMID- 9250987
TI  - Use of magnetic field effects to study coenzyme B12-dependent reactions.

PMID- 9250988
TI  - Analysis of cobalamin and cobalamin analogs by gas chromatography-mass
      spectrometry.

PMID- 9250990
TI  - Quantitative methods for measurement of transcobalamin II.

PMID- 9250989
TI  - Expression of functional intrinsic factor using recombinant baculovirus.

PMID- 9250991
TI  - Molecular methods for analysis and expression of transcobalamin II.

PMID- 9250992
TI  - Purification, membrane expression, and interactions of transcobalamin II
      receptor.

PMID- 9250993
TI  - Purification and characterization of aquacobalamin reductase from Euglena
      gracilis.

PMID- 9250994
TI  - Purification and characterization of aquacobalamin reductases from mammals.

PMID- 9250995
TI  - Continuous coupled assay for 5-aminolevulinate synthase.

PMID- 9250996
TI  - Dipyrromethane cofactor assembly of porphobilinogen deaminase: formation of
      apoenzyme and preparation of holoenzyme.

PMID- 9250997
TI  - Coupled assay for uroporphyrinogen III synthase.

PMID- 9250998
TI  - Expression and purification of mammalian 5-aminolevulinate synthase.
AB  - We have described a procedure for production and purification of recombinant,
      mature-length mouse ALAS-2. The fact that E. coli utilizes the C5 path for ALA
      production means that there is no problem with contamination of the recombinant
      ALAS-2 by host cell enzyme, such as one may have with a yeast expression system.
      While the detailed procedure produces enzyme in good yield with relatively common
      protein purification techniques, future expression systems may be developed to
      take advantage of the rapid purification achieved by the use of a 6-histidine
      (His6) aminoterminal tag and metal chelate chromatography. Such approaches in
      this laboratory with protoporphyrinogen oxidase, coproporphyrinogen oxidase, and
      uroporphyrinogen decarboxylase have resulted in the production and purification
      of enzymes whose kinetic and physical parameters are essentially identical to
      those of proteins lacking the His6 tag.

PMID- 9251000
TI  - Purification and properties of uroporphyrinogen decarboxylase from human
      erythrocytes.

PMID- 9250999
TI  - Expression, purification, and characteristics of mammalian protoporphyrinogen
      oxidase.

PMID- 9251001
TI  - Purification and properties of coproporphyrinogen III oxidase from bovine liver.

PMID- 9251002
TI  - Purification and properties of coproporphyrinogen III oxidase from yeast.

PMID- 9251003
TI  - Expression, purification, and characterization of recombinant mammalian
      ferrochelatase.

PMID- 9251004
TI  - Structural characterization of modified folates in Archaea.

PMID- 9251005
TI  - Biokinetic analysis of vitamin absorption and disposition in humans.

PMID- 9251006
TI  - In situ kinetics: an approach to recommended intake of vitamin C.

PMID- 9251007
TI  - Purification and reconstitution of cyclin-dependent kinase 2 in four states of
      activity.

PMID- 9251008
TI  - Purification of recombinant cyclin B1/cdc2 kinase from Xenopus egg extracts.

PMID- 9251009
TI  - Protein phosphorylation analysis by electrospray ionization-mass spectrometry.

PMID- 9251010
TI  - Cloning cell cycle regulatory genes by transcomplementation in yeast.

PMID- 9251011
TI  - Fluorescence-activated cell sorting of transfected cells.

PMID- 9251012
TI  - Microinjection of antibodies into mammalian cells.

PMID- 9251013
TI  - Small pool expression screening: identification of genes involved in cell cycle
      control, apoptosis, and early development.

PMID- 9251014
TI  - Localization of cell cycle regulators by immunofluorescence.

PMID- 9251015
TI  - Chemical inhibitors of cyclin-dependent kinases.

PMID- 9251016
TI  - Identifying human homologs of cell cycle genes using dbEST and XREFdb.

PMID- 9251017
TI  - Gene identification using the yeast two-hybrid system.

PMID- 9251018
TI  - Use of tetracycline-controlled gene expression systems to study mammalian cell
      cycle.

PMID- 9251019
TI  - Regulation of mammalian cyclin-dependent kinase 2.

PMID- 9251021
TI  - Functional analysis of E2F transcription factor.

PMID- 9251020
TI  - Assay for activity of mammalian cyclin D-dependent kinases CDK4 and CDK6.

PMID- 9251022
TI  - Analysis of mammalian Cdc37, a protein kinase targeting subunit of heat shock
      protein 90.

PMID- 9251023
TI  - Purification and analysis of CIP/KIP proteins.

PMID- 9251024
TI  - Functional dissection of p53 tumor suppressor protein.

PMID- 9251025
TI  - Reconstitution of mammalian CDK-activating kinase.

PMID- 9251026
TI  - Characterization of mammalian NIMA-related kinases.

PMID- 9251027
TI  - Generation of phosphorylated cyclin-dependent kinase 2 and functional
      characterization of threonine-160-specific phosphatase KAP.

PMID- 9251028
TI  - Isolation and characterization of temperature-sensitive mammalian cell cycle
      mutants.

PMID- 9251029
TI  - Use of conditional promoters for expression of heterologous proteins in
      Saccharomyces cerevisiae.

PMID- 9251031
TI  - Alpha-factor synchronization of budding yeast.

PMID- 9251030
TI  - Flow cytometric analysis of DNA content in budding yeast.

PMID- 9251032
TI  - Elutriation of budding yeast.

PMID- 9251034
TI  - Cell-free ubiquitination of cell cycle regulators in budding yeast extracts.

PMID- 9251033
TI  - Functional analysis of FAR1 in yeast.

PMID- 9251035
TI  - Genomic footprinting of budding yeast replication origins during the cell cycle.

PMID- 9251036
TI  - Preparation of active Cdc7/Dbf4 kinase from yeast cells.

PMID- 9251037
TI  - Analysis of budding yeast kinases controlled by DNA damage.

PMID- 9251038
TI  - Use of cdc13-1-induced DNA damage to study effects of checkpoint genes on DNA
      damage processing.

PMID- 9251039
TI  - The spindle assembly checkpoint in budding yeast.

PMID- 9251040
TI  - Genetic and physiological analysis of DNA replication in fission yeast.
AB  - Studies on DNA replication in S. pombe have provided powerful insights into the
      way in which the genome of this model eukaryote is replicated and how the
      replication process is controlled. These studies have been facilitated by the
      simplicity and range of methods available in this organism for physiological and
      genetic analysis of DNA replication mutants. In the future, continued focus on
      the analysis of such mutants, coupled with increasingly sophisticated biochemical
      investigation of the processes of DNA replication in both wild-type and mutant
      cells, will ensure continued rapid progress in this area.

PMID- 9251041
TI  - Use of green fluorescent protein for intracellular protein localization in living
      fission yeast cells.

PMID- 9251042
TI  - Analysis of radiation-sensitive mutants of fission yeast.

PMID- 9251043
TI  - Cytokinesis in fission yeast Schizosaccharomyces pombe.

PMID- 9251044
TI  - Stress-activated protein kinase pathway in cell cycle control of fission yeast.

PMID- 9251045
TI  - Characterization of NIMA protein kinase in Aspergillus nidulans.

PMID- 9251046
TI  - Xenopus replication assays.

PMID- 9251047
TI  - Characterization of the Xenopus replication licensing system.

PMID- 9251048
TI  - Regulation of Xenopus Cdc25 protein.

PMID- 9251049
TI  - Characterization of spindle assembly checkpoint in Xenopus egg extracts.

PMID- 9251050
TI  - Mechanisms of Xenopus oocyte maturation.

PMID- 9251051
TI  - Apoptosis in Xenopus egg extracts.

PMID- 9251052
TI  - Preparation of clam oocyte extracts for cell cycle studies.

PMID- 9251053
TI  - Mitotic protein kinases in Drosophila embryos.

PMID- 9251054
TI  - Isolation of a new Orientia tsutsugamushi serotype.
AB  - Orientia tsutsugamushi, the etiological agent of scrub typhus, is an
      antigenically diverse organism and many serologically distinct strains have been
      identified. The 56 kDa protein of O. tsutsugamushi, a major protein in the outer
      membrane, has been thought to be responsible for this antigenic variability. A
      strain of O. tsutsugamushi isolated in Korea cross-reacted with both Gilliam
      strain-specific and Karp strain-specific monoclonal antibodies. When its 56 kDa
      protein gene was cloned and analyzed, its sequence showed variation especially
      between 1,200 and 1,250 bp, showing that this isolate is a new O. tsutsugamushi
      strain.

PMID- 9251055
TI  - Unification of the genera Serpulina and Brachyspira, and proposals of Brachyspira
      hyodysenteriae Comb. Nov., Brachyspira innocens Comb. Nov. and Brachyspira
      pilosicoli Comb. Nov.
AB  - The phylogenetic positions of Serpulina hyodysenteriae, Serpulina innocens,
      Serpulina pilosicoli and Brachyspira aalborgi were studied. Complete 16S
      ribosomal DNA sequences of these three species and B. aalborgi revealed that
      their 16S rDNA sequences were related more than 96.0%. The mol% guanine plus
      cytosine (G+C) of B. aalborgi DNA was 27.1, and was similar to those of the 3
      members of the genus Serpulina. The homologous rates using 31P-labeled B.
      aalborgi chromosome DNA in DNA-DNA reassociation tests were 22.0% to S.
      hyodysenteriae, 19.1% to S. innocens and 17.2% to S. pilosicoli. Therefore, we
      propose to transfer the three species of the genus Serpulina to the genus
      Brachyspira. Descriptions of Brachyspira hyodysenteriae comb. nov., Brachyspira
      innocens comb. nov. and Brachyspira pilosicoli comb. nov., and an emended
      description of B. aalborgi are given. Phenotypic characteristics of the 4 members
      of the genus Brachyspira were also studied. They fermented fructose, galactose,
      glucose, lactose, maltose, mannose, raffinose and trehalose; however, B. aalborgi
      did not ferment raffinose. All of them hydrolyzed esculin but did not produce
      indole except for B. hyodysenteriae. The protein profile of B. aalborgi was
      different from those of the four strains of B. hyodysenteriae, B. innocens and B.
      pilosicoli, but the heavy bands with molecular sizes of 49.4 and 52.3 kDa of B.
      aalborgi were quite similar to those of B. innocens in the points of quantity and
      molecular size. In immunoblotting tests, B. aalborgi reacted well with anti-B.
      innocens and B. pilosicoli sera, but reacted weakly with anti-B. hyodysenteriae
      serum. Only one heavy band and several faint bands were revealed by the reaction
      between B. aalborgi and anti-B. hyodysenteriae serum, and the heavy band was
      common among these strains.

PMID- 9251056
TI  - Genetic identification of members of the genus Corynebacterium at genus and
      species levels with 16S rDNA-targeted probes.
AB  - 16S rRNA gene-targeted probes were designed for the identification of
      corynebacteria at the genus and species levels. The genus-specific probe
      hybridized all clinically important members of the genus Corynebacterium and
      could distinguish them from other coryneform bacteria and phylogenetically
      related high G+C% gram-positive bacteria, including Actinomyces, Rhodococcus,
      Gordona, Nocardia, Streptomyces, Brevibacterium and Mycobacterium. The species
      specific probes for C. jeikeium and C. diphtheriae could differentiated these two
      species from other members of this genus. The probes were used to select
      corynebacteria among gram-positive clinical isolates which had been tentatively
      identified as corynebacteria by biochemical tests. We screened 59 strains with
      the genus-specific probe; 51 strains hybridized to the genus-specific probe, 8
      did not. Of the 51 strains that hybridized to the genus-specific probe, 1
      hybridized to the C. diphtheriae species probe and 13 hybridized to the C.
      jeikeium species probe. The 8 strains that did not hybridize to the genus probe
      were further characterized by analyzing cell wall diaminopimelic acid and partial
      16S rRNA sequencing. The results indicated that these strains were distributed in
      the genera Arthrobacter and Brevibacterium.

PMID- 9251057
TI  - Overproduction of Campylobacter ferritin in Escherichia coli and induction of
      paracrystalline inclusion by ferrous compound.
AB  - The ferritin gene (cft) of Campylobacter jejuni was overexpressed in cells of
      Escherichia coli using a T7 RNA polymerase expression system. Many round
      particles which were the same size as the ferritin particles purified from C.
      jejuni were observed in the lysate of the cft-overexpressed E. coli cells. Since
      most of them were devoid of a central electron dense core consisting of ferric
      irons, the Campylobacter ferritins over-produced in E. coli seemed to be
      apoferritin. When large amounts of ferrous iron (supplied as FeSO4) were added to
      culture medium, the cft-overexpressed cells formed large inclusion bodies of
      paracrystalline arrays comprised of ferritin particles with central electron
      dense cores. The addition of ferric irons did not produce paracrystalline
      inclusion.

PMID- 9251058
TI  - Subcellular localization of the major autolysin, ATL and its processed proteins
      in Staphylococcus aureus.
AB  - The Staphylococcus aureus autolysin gene, atl, encodes a unique 138-kDa protein
      (ATL) with amidase and glucosaminidase domains. ATL has been suggested to undergo
      proteolytic processing to generate two extracellular peptidoglycan hydrolases, 51
      kDa endo-beta-N-acetylglucosaminidase (51-kDa GL) and 62-kDa N-acetylmuramyl-L
      alanine amidase (62-kDa AM). To investigate cell-associated bacteriolytic enzymes
      for atl gene products, proteins were extracted from the cells as follows. The
      cells were exposed to 3 M LiCl followed by 4% SDS. Thereafter, the cells were
      disrupted and again extracted with 4% SDS. Whole SDS-stable cell-associated
      bacteriolytic proteins were extracted without disrupting the cells. Exposure to 3
      M LiCl released major 138-, 115-, 85-, 62- and 51-kDa bacteriolytic proteins, and
      subsequent 4% SDS extraction released major 138- and 115-kDa bacteriolytic
      proteins. These bacteriolytic proteins were missing in extracts of atl mutant
      RUSAL2 (S. aureus RN450 atl::Tn551). Immunoblotting studies suggest that these
      are all atl gene products: the 138-kDa protein is an ATL with a cleaved signal
      sequence; the 115- and 85-kDa proteins are intermediates; and the 51- and 62-kDa
      proteins are cell-associated 51-kDa GL and 62-kDa AM, respectively. The trypsin
      susceptibility of these proteins suggests that they are located outside the cell
      membrane. Differences in extractability and immunoelectron microscopic studies
      suggest that atl gene products are associated with cells in two different ways,
      LiCl extractable and non extractable. We suggest that the 138-kDa ATL undergoes
      processing through intermediate proteins (115- and 85-kDa proteins) to mature as
      the active cell cluster-dispersing enzymes 51-kDa GL and 62-kDa AM on the cell
      surface.

PMID- 9251059
TI  - Amplification of a full-length Borna disease virus (BDV) cDNA from total RNA of
      cells persistently infected with BDV.
AB  - We have developed a novel reverse transcriptase-polymerase chain reaction (RT
      PCR) to amplify the full-length 8.9 kilobase (kbp) cDNA of the Borna disease
      virus (BDV) RNA genome from the total cellular RNA of MDCK cells persistently
      infected with BDV (MDCK/BDV). Antigenomic BDV cDNA was reverse transcribed using
      a 53-mer oligonucleotide primer, corresponding to the 5'-terminus of a putative
      3'-leader sequence of the BDV RNA genome, for 2 hr at 42 C followed by 30 min at
      55 C. PCR was performed in the presence of this 53-mer antigenomic primer and a
      25-mer primer, corresponding to the 3'-terminus of the BDV antigenomic cDNA, by
      use of an rTth DNA polymerase with proof-reading activity. The amplified full
      length BDV cDNA was detected in as little as 20 ng of total cellular RNA of
      MDCK/BDV. This RT-PCR method should be a useful technique to study the molecular
      quasispecies of BDV.

PMID- 9251060
TI  - Moraxella (Branhamella) catarrhalis adherence to human bronchial and
      oropharyngeal cells: the role of adherence in lower respiratory tract infections.
AB  - To study the role of Moraxella (subgenus Branhamella) catarrhalis (B.
      catarrhalis) adherence to airway cells in lower respiratory tract infections, the
      in vitro attachments of B. catarrhalis to upper airway (oropharyngeal) and lower
      airway (bronchial) epithelial cells were compared. The adherence of 4 strains (1
      nonfimbriated and 3 fimbriated) of B. catarrhalis to respiratory tract epithelial
      cells collected from 11 patients with chronic pulmonary disease (CPD) and 11
      healthy individuals was evaluated. Both the fimbriated and nonfimbriated strains
      showed increased attachment to oropharyngeal cells in the CPD patients (mean +/-
      SEM; 25.0 +/- 3.2/cell; P < 0.01) when compared to the control subjects (12.1 +/-
      1.1/cell). On the average, the attachment to bronchial cells was 6.1 to 13.6
      times greater per surface area (bacteria/micron2) than the attachment to
      oropharyngeal cells. The fimbriated strains tended to adhere in higher numbers to
      bronchial cells (19.0 +/- 1.8/cell) than the nonfimbriated strain (8.7 +/-
      1.2/cell), although there was no difference between the CPD and control groups.
      In conclusion, the attachment of B. catarrhalis to oropharyngeal cells may be an
      enhancing factor for colonization in the upper respiratory tract in patients with
      CPD, and elevated adherence of the bacteria to bronchial cells may suggest
      pathogenic importance when mucociliary function is impaired.

PMID- 9251061
TI  - Cellular immune responses to cell wall peptidoglycan associated protein antigens
      in tuberculosis patients and healthy subjects.
AB  - We have isolated cell wall peptidoglycan associated proteins (CW-Pr) of
      Mycobacterium tuberculosis H37Ra by chemical treatment with
      trifluoromethanesulfonic acid:anisole (2:1), which further resolved into 71, 60
      and 45 kDa proteins on SDS-PAGE. A study was carried out to investigate the
      immunoreactivity of these proteins with blood samples from 4 categories,
      including 15 tuberculous patients (TB), 5 tuberculous patients on ATT (TBT), 10
      PPD non-reactive healthy controls (HPPD-) and 11 PPD reactive healthy controls
      (HPPD+). Comparing the proliferative responses to cell wall protein antigens, it
      was observed that the 71 kDa protein gave maximum stimulation with PBMCs from the
      TB and HPPD+ groups. The adherent PBMCs from the TB group also demonstrated
      enhanced phagocytosis, particularly in the presence of 71 and 45 kDa proteins,
      and the phagocytic index was significantly higher (P < 0.05) than the TBT group.
      However, PBMCs from of the groups recognized the 60 kDa cell wall antigen. Our
      results suggest that the 71 kDa protein from the cell wall of M. tuberculosis is
      highly immunogenic.

PMID- 9251062
TI  - Prevalence of genotypes of Orientia tsutsugamushi in patients with scrub typhus
      in Miyazaki Prefecture.
AB  - The genotypes of Orientia tsutsugamushi in patients with scrub typhus in Miyazaki
      Prefecture were examined by polymerase chain reaction (PCR) and the restriction
      fragment length polymorphism method. Specific patterns for genotypes Irie,
      Hirano, Tazume and Yoshimura were detected in 26, 6, 5 and 2 of 39 DNA samples
      obtained from peripheral blood mononuclear cells, respectively. DNA sequences of
      the PCR products from the Tazume strain were genetically very close to the Hirano
      strain and the Yoshimura strain was also very close to the Karp strain.
      Furthermore, the DNA sequences from the Irie and Tazume strains were completely
      homologous to the reported sequences of the Kawasaki and Kuroki strains,
      respectively.

PMID- 9251063
TI  - Sequence analysis of the influenza virus strain A/shearwater/Australia/1/72
      (H6N5).
AB  - Analysis of the NS and M genes of the archetype H6N5 influenza virus strain
      A/shearwater/Australia/1/72 shows it to be a typical example of the avian host
      reservoir, containing Old World/Eurasian internal proteins with divergent surface
      proteins, which is a potential source of new pandemic strains.

PMID- 9251064
TI  - Movement Disorders Cochrane Collaborative Review Group.
AB  - Evidence-based medicine is the process of systematically finding, appraising, and
      applying contemporaneous research findings as the basis for clinical decisions.
      The individual clinician is too busy to perform this long and arduous task across
      the whole of their specialty, so they must rely on the highest quality reviews
      available in the literature. The Cochrane Collaboration is an international
      network of individuals preparing, maintaining, and disseminating systematic
      reviews of trials of all health care interventions. We examine the work of the
      Collaboration and the major method it uses to disseminate systematic reviews
      through the Cochrane Library. The rationale for the Cochrane Movement Disorders
      Group is discussed, and its management structure outlined.

PMID- 9251065
TI  - The emerging role of clozapine in the treatment of movement disorders.
AB  - Clozapine, the only commercially available atypical neuroleptic, is approved for
      the treatment of schizophrenic patients who are unresponsive to or intolerant of
      typical neuroleptics. It has an unusual pharmacologic profile compared with
      standard neuroleptics, and it follows that clinical response to this drug is also
      different. It has shattered the notion that a drug must be capable of inducing or
      worsening parkinsonism to be a potent antipsychotic. Based on these findings, it
      is being used increasingly by neurologists for psychiatric and nonpsychiatric
      problems in patients with movement disorders. The most common use for clozapine
      among neurologists is in the management of drug-induced psychosis in Parkinson's
      disease (PD). This problem has been a source of increased morbidity and mortality
      in PD because of a lack of adequate therapeutic intervention. At this time,
      because of success in numerous open trials, with improvement of > 80% of
      patients, clozapine therapy for psychosis in PD is becoming the standard of care.
      It also appears to be of value in the management of some motor features of PD,
      including tremors and dyskinesia and possibly even sensory symptoms such as
      akathisia and pain. The literature also suggests that clozapine may be of
      potential benefit in hyperkinetic movement disorders including essential tremor,
      Huntington's disease, and tardive dyskinesia. We review the current data
      concerning the use of clozapine in patients with these movement disorders and
      others.

PMID- 9251066
TI  - Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with
      Parkinson's disease.
AB  - The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical
      response, and drug tolerability was studied in 13 patients with Parkinson's
      disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral
      catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double
      blind study. An L-Dopa test was performed on 3 study days. The first study day
      was with L-Dopa/benserazide only (control), the second after 14 days of treatment
      with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination
      with either selegiline (10 mg daily) or placebo. After a 2-week washout period,
      selegiline and placebo treatments were switched, and the third study day was
      after 14 days of treatment. During the study days, clinical response was
      evaluated at 30-min intervals for 6 h, by using the motor score of the Unified
      Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure
      measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O
      methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA),
      dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG).
      Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from
      platelets and erythrocytes, respectively. Entacapone improved the clinical
      response to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The
      improvement was more marked during combined selegiline and entacapone treatment
      than with entacapone alone (p < 0.01). Entacapone significantly increased plasma
      L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with
      selegiline and placebo. Selegiline partially inhibited the entacapone-induced
      increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not
      change. Entacapone decreased erythrocyte COMT activity by > 35% (p < 0.001), and
      platelet MAO-B activity was almost completely inhibited by selegiline (p <
      0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep
      when receiving selegiline treatment. Otherwise no differences in adverse events,
      mean daily blood pressures, or other safety parameters were observed between
      selegiline and placebo treatments. Our results suggest that entacapone can be
      safely administered together with L-Dopa and selegiline in patients with PD,
      although further studies with larger number of patients and longer treatment
      periods are necessary to confirm this finding.

PMID- 9251067
TI  - Sleep benefit in Parkinson's disease.
AB  - Sleep benefit (SB) In Parkinson's disease (PD) is not well characterized. To
      determine SB frequency, as well as to characterize and correlate it with other
      disease variables, we evaluated prospectively a consecutive series of 312 PD
      patients by means of a structured questionnaire: 55% reported having SB and 35%
      reported that awakening was their best time of the day. Because of SB, 21% of the
      entire population were able to skip or delay medication. The mean duration of the
      phenomenon was 85.4 +/- 67 min. Patients with SB were significantly older (p <
      0.0002), had disease longer (p < 0.05), and were often men (chi 2 = 3.5, df 1, p
      = 0.05). Patients with SB took sleep medication with similar frequency as those
      without SB. There were no differences in hours of sleep or sleep latency. Sleep
      problems such as nightmares or somnambulism, but not the number of sleep
      awakenings, were similar in both groups. In conclusion, SB is a frequent
      phenomenon, especially in men, elderly patients, and patients with longer disease
      duration. SB enables the morning L-dopa dose to be postponed in approximately 50%
      of patients.

PMID- 9251069
TI  - The "cold hands sign" in multiple system atrophy.
AB  - Patients with multiple system atrophy (MSA) often have cold, dusky, violaceous
      hands, with poor circulatory return after blanching by pressure. We therefore
      compared hand skin temperature in nine age-matched subjects with probable MSA, 10
      with idiopathic Parkinson's disease (PD), and 10 healthy controls both at rest
      and following a standard cooling procedure. Baseline skin temperature in the MSA
      group was significantly lower than in both the PD and control groups, and four of
      the nine MSA patients were colder at baseline than the coldest control value.
      After cooling, the MSA group also showed a significantly greater reduction in
      skin temperature than the PD group. The rate of skin temperature recovery did not
      differ between the three groups, although the MSA group required more time to
      return completely to their baseline temperature. Changes in skin colour or
      temperature are easily detected, and suggest a defect in neurovascular control of
      distal extremities. The "cold hands sign" is another clinical "red flag" that
      helps to raise the suspicion of MSA.

PMID- 9251068
TI  - Urinary disturbances in striatonigral degeneration and Parkinson's disease:
      clinical and urodynamic aspects.
AB  - Although urinary disturbances are more frequent in multiple system atrophy (MSA)
      than in Parkinson's disease (PD), the striatonigral degeneration (SND) type of
      MSA is difficult to distinguish from PD, especially when the latter is associated
      with orthostatic hypotension or urinary symptoms. The pattern of urinary symptoms
      and urodynamic dysfunction was analyzed in 15 SND and 35 PD patients with urinary
      complaints. In SND, dysuria with or without chronic retention, frequently
      associated with a hypoactive detrusor and low urethral pressure, permitted early
      and reliable diagnosis. In PD, urgency to void, with or without difficulty
      voiding, but without chronic retention, associated with detrusor hyperreflexia
      and normal urethral sphincter function, predominated. In clinical practice, the
      study of urinary symptoms and bladder function may help to distinguish SND from
      PD in patients with urinary disturbances.

PMID- 9251071
TI  - Vomiting and retching in Gilles de la Tourette syndrome: a report of ten cases
      and a review of the literature.
AB  - Retching and vomiting are common symptoms in childhood. We describe the cases of
      10 patients with Gilles de la Tourette syndrome (GTS) for whom vomiting or
      retching tics were part of the clinical picture, and discuss other instances
      where retching and vomiting occur with neuropsychiatric or movement disorders.

PMID- 9251070
TI  - Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological
      findings in genetically confirmed North American and European pedigrees.
AB  - Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant
      disorder that clinically overlaps with Huntington's disease (HD) and manifests
      combinations of chorea, myoclonus, seizures, ataxia, and dementia. DRPLA is
      caused by a CAG triplet repeat (CTG-B37) expansion coding for polyglutamine on
      chromosome 12 and exhibits the genetic phenomenon of anticipation. This
      neurodegenerative disease has only rarely been reported in non-Japanese
      pedigrees, and there are only a few neuropathological studies in genetically
      confirmed patients. We report 10 cases of DRPLA from two North American and two
      British pedigrees in which CTG-B37 expansions have been demonstrated within each
      kindred (54-83 repeats), individually in 8 of the 10 cases, and describe the
      neuropathological findings in 4 cases. Members of DRPLA kindreds have a wide
      range of clinical phenotypes and markedly variable ages at onset. The
      neuropathological spectrum is centered around the cerebellifugal and pallidofugal
      systems, but neurodegenerative changes can be found in many nuclei, tracts, and
      systems. Evidence of CTG-B37 triplet repeat expansion should be sought in HD-like
      cases that are negative for expanded triplet repeats within the HD IT15 gene or
      in autopsy cases with degeneration of the dentatorubral or pallidoluysian
      systems.

PMID- 9251072
TI  - Saccades in Gilles de la Tourette's syndrome.
AB  - Gilles de la Tourette's syndrome (GTS) is presumed to be an inherited disorder
      with an unclear pathophysiology. An involvement of the basal ganglia is
      suspected. Besides vocal tics, one of the main symptoms is the presence of motor
      tics. As eye movements are a specialized part of the motor system, we
      investigated whether they differed in some typical way in GTS patients. To study
      the control of saccades in GTS, different paradigms were used to elicit saccades,
      which were either externally triggered and visually guided or internally
      triggered and without visual target. GTS patients (n = 10) showed a significant
      increase of the latency of antisaccades, a highly impaired performance of
      sequences of memory-guided saccades, and an isolated reduction of the peak
      velocity in the antisaccades. Overall the results were similar to those found
      with similar paradigms in patients with Huntington's disease (HD). In analogy to
      the known pathology of HD, these findings can be attributed to ascending loops
      from the basal ganglia that inappropriately activate the frontal cortex,
      especially some of the eye movement-related areas there. This impairment seems to
      be a rather specific effect, since some oculomotor features that are preserved by
      structures of the frontal cortex, such as the effect of a fixation target on
      saccadic latency ("gap effect"), were normal.

PMID- 9251073
TI  - Hand tremor in patients with spasmodic torticollis.
AB  - The occurrence of hand tremors in patients with spasmodic torticollis (ST) was
      investigated in 55 patients by clinical and quantitative measurements. Ten
      patients had first-order or second-order relatives affected with postural tremor.
      Although 40% of the patients had a medical history and clinical findings for mild
      postural and action tremor of the hands, only four had moderate tremor
      amplitudes. One patient had a severe tremor, including resting tremor, and two
      had mild voice tremor. A positive correlation was found between hand and head
      tremor. Patients with hand tremor were younger at the onset of ST than were those
      without. The mean amplitudes of postural tremor were only slightly higher than
      for the controls and much smaller than those found in classic essential tremor.
      The tremor caused only mild disabilities. The tremor frequencies were
      indistinguishable from physiologic tremor. Further analysis of the tremor records
      showed evidence for physiologic tremor mechanisms only. We conclude that slightly
      enhanced postural hand tremors are common in ST but have a low amplitude and are
      only rarely clinically relevant for ST patients. Although the present data
      support the notion of an enhanced risk of postural tremor in families of patients
      affected with ST, none of the criteria allowed the separation of the hand tremor
      of ST from other postural/action tremors and especially from enhanced physiologic
      tremor. Thus, the present data do not support the classification of hand tremor
      in ST as either "dystonic" or essential tremor.

PMID- 9251074
TI  - Lateralization of the P22/N30 component of somatosensory evoked potentials of the
      median nerve in patients with cervical dystonia.
AB  - Somatosensory evoked potentials (SEPs) of the median nerve were recorded in 40
      patients suffering from cervical dystonia and in 40 healthy volunteers as a
      control. Before recording the median nerve SEPs, polymyographic recordings were
      performed in all patients with cervical dystonia. The activity of cervical
      muscles was recorded, and the leading muscle of cervical dystonia was determined.
      Patients were divided into two groups according to the results of polymyography.
      The leading muscle was sternocleidomastoid in the first group and the splenius
      capitis in the second group. Patient SEPs were recorded during abnormal head
      rotation. SEPs in 20 healthy volunteers were recorded with the head in the middle
      position. SEPs of another 20 healthy volunteers were recorded with the head
      rotated 60 degrees to the right. The mean peak-to-peak amplitude values of the
      precentral P22/N30 complex and the mean ratio of the P22/N30 amplitudes between
      both hemispheres were calculated in the F3 (F4) and C3' (C4') electrode positions
      in all four groups. No significant lateralization of the precentral P22/ N30
      component was found in either group of healthy volunteers. In dystonic patients
      in whom the sternocleidomastoid was determined as the leading muscle of dystonia,
      a statistically significant lateralization of the P22/N30 component toward the
      ipsilateral side of the leading muscle was found. In the group with the splenius
      capitis determined as the leading muscle of dystonia, a statistically significant
      lateralization of the P22/N30 component toward the contralateral side of the
      leading muscle was found. The possibility that the precentral cortex is activated
      differently in cervical dystonia patients who have different muscle patterns of
      dystonia is discussed.

PMID- 9251075
TI  - Perception of spatial orientation in spasmodic torticollis. Part I: The postural
      vertical.
AB  - Estimates of points of entering and exiting from upright posture were obtained
      from 25 seated, restrained patients with idiopathic spasmodic torticollis (ST)
      and matched normal subjects exposed to cycles of 1.5 degrees/s tilts in a flight
      simulator. Estimates were obtained for displacements in roll and pitch about
      upright and for yaw tilts about a rostrocaudal, "barbecue," axis with the
      subjects supinated. For both pitch and roll, normal subjects estimated entering
      upright when they were still approximately 1 degree from machine upright and
      perceived themselves to be upright through a mean arc of 6 degrees. In barbecue
      tilt, entering upright was estimated at 0.2 degree for an arc of 6 degrees.
      Patients estimated entering upright at 2.8 degrees in roll and 3 degrees in pitch
      but estimated exiting upright at the same tilt as normal subjects; that is, they
      were less specific in detecting verticality. Patients were normal in barbecue
      tilt. No relationship between tilt estimates and head deviation was found. There
      were no differences between normal subjects when tested with their head in normal
      posture and with an assumed tilt of 20 degrees. Normal subjects probably based
      their estimates on combined vestibular-somatosensory signals, whereas torticollis
      patients appeared to derive more from a vestibular signal. However, patients
      referred the vestibular signals to the trunk long axis when asked to indicate the
      whole-body vertical. The findings suggest disruption of the normal combined
      vestibuloproprioceptive mechanism for detecting body uprightness in ST.

PMID- 9251076
TI  - Teaching tape for the motor section of the Toronto Western Spasmodic Torticollis
      Scale.
AB  - The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) assesses the
      character and severity of cervical dystonia (CD). We developed a teaching tape of
      the TWSTRS scoring for the motor symptoms of CD. The tape provides investigators
      with visual representations of each component of the motor section of the TWSTRS
      as agreed upon by three independently scoring raters. The rate of agreement for
      the nondichotomous components was always significant, with a Kendall's
      coefficient of concordance W ranging between 0.98 and 0.76 (p < 0.01 for all
      measures). For the two dichotomous components, a weighted kappa coefficient was
      also significant at 0.86 for lateral shift and 0.89 for sagittal shift (p < 0.01
      for both measures). Scale deficiencies identified by the raters were an explicit
      definition of midline for assessment of range of motion, the absence of a
      separate scoring category assessing dystonic tremor, and the specification of
      duration for the effect of sensory tricks. These observations should be taken
      into account in future revisions of the TWSTRS and in refinements of other rating
      scales for CD.

PMID- 9251078
TI  - Severe tardive dystonia: treatment with continuous intrathecal baclofen
      administration.
AB  - Treatment of tardive dystonia with oral baclofen produces ambivalent and overall
      disappointing results. However, because only a small proportion of the baclofen
      penetrates into the central nervous system when administered orally, we tested
      whether it is possible to increase the efficacy of treatment by continuous
      intrathecal infusion of baclofen (CITB) in a patient with severe tardive axial
      dystonia unresponsive to conventional therapy. A dose of 100 micrograms/day
      improved muscle tone, head control, posture, and walking distance;
      electromyography showed a marked decrease of dystonic muscle activity with fully
      preserved voluntary muscle activity, and the patient reported substantial
      reduction of pain. Apart from some minor discomfort at the site of operation, no
      side effects were noted. Further studies should be encouraged to evaluate the
      usefulness of CITB for other patients with severe and otherwise untreatable
      tardive dystonia.

PMID- 9251077
TI  - Neurophysiological investigations in patients with head tremor.
AB  - We studied 30 patients whose primary complaint was head tremor in an attempt to
      characterize neurophysiological aspects of their abnormal movement. Based on
      family medical history and physical examination, 23 patients had definite or
      probable essential tremor (essential head tremor, EHT). The remaining seven had
      mild dystonic signs accompanying their head tremor (head tremor plus dystonic
      signs, HT + DS). We recorded head movement and the electromyographic (EMG)
      activity of the sternomastoid and splenius capitis muscles, determined the
      spontaneous blinking rate, and measured the excitability recovery curve of the
      blink reflex and of the masseteric inhibitory reflex. All patients had tremor
      bursts at a frequency ranging between 3 and 9 Hz in at least one of the muscles
      examined. The predominant pattern seen when patients were sitting relaxed and
      facing forward was that of synchronized EMG bursts in both splenius capitis
      muscles. Maintenance of extreme head postures demonstrated two types of
      additional abnormalities: type 1 (enhancement of tremor), which was observed in
      11 patients (47.8%) with EHT and in two (28.5%) with HT + DS; and type 2
      (activation of neck muscles not required for maintenance of the posture), which
      was observed in two patients (8.7%) with EHT and in five (71.5%) with HT + DS
      (chi 2 = 26.4; p < 0.001). Mean blinking rate per minute was 24.9 +/- 14.6 in
      patients with EHT and 42.3 +/- 10.5 in patients with HT + DS (paired t test, p =
      0.001). The blink reflex and masseteric inhibitory reflex excitability recovery
      curves showed an abnormal interneuronal excitability enhancement in seven (30.4%)
      of the 23 patients with EHT and in two (28.5%) of the seven with HT + DS (chi 2 =
      3.1; p > 0.05). Abnormal patterns of EMG activity of the neck muscles correlated
      well with the presence of mild dystonic signs. However, the analysis of brainstem
      interneuronal excitability did not enable recognition of those patients with head
      tremor who could potentially develop cervical dystonia. The enhancement of
      brainstem interneuronal excitability found in approximately 30% of patients with
      head tremor could be related to plastic changes triggered by increased activity
      of the cranial muscles.

PMID- 9251079
TI  - A Tourette-like syndrome following cardiopulmonary bypass and hypothermia: MRI
      volumetric measurements.
AB  - We present the case of an adolescent boy who developed a variety of simple and
      complex motor and vocal tics (Tourette-like syndrome), along with inattentiveness
      and obsessive-compulsive behaviors after cardiac surgery with cardiopulmonary
      bypass and profound hypothermia. A single photon emission computed tomography
      study 2 months after surgery showed reduced uptake in the left hemisphere and 2
      years later a perfusion defect in the basal ganglia. Serial magnetic resonance
      imaging (MRI) studies were normal. Volumetric MRI studies were obtained 4 years
      after surgery and compared with published values for normal individuals and
      children with Tourette syndrome (TS), including subsets matched for age, sex, and
      handedness. Measurement of basal ganglia structures showed a right-dominant
      asymmetry of the caudate and putamen, in part similar to findings previously
      reported in patients with TS. Other volumetric abnormalities included a > 2-SD
      reduction of cortical gray matter, a small decrease of total cerebral volume, and
      increase in cerebral white matter. Although a variety of neurological problems
      may occur after cardiopulmonary bypass, to our knowledge this case represents the
      first report of a chronic tic disorder following cardiac surgery with
      cardiopulmonary bypass and hypothermia.

PMID- 9251080
TI  - AIDS dementia complex with generalized myoclonus.
AB  - Focal and segmental, but not generalized, myoclonus have been described with
      human immunodeficiency virus (HIV) infection. We describe three patients with
      generalized myoclonus and acquired immunodeficiency syndrome (AIDS) dementia
      complex. In each, myoclonus persisted until death, invariably after a course of a
      few months. In two patients, myoclonus was elicited by sudden auditory stimuli
      and resembled a startle response. This form of myoclonus may be subcortical in
      origin. We suggest that the AIDS dementia complex be included among the causes of
      myoclonic dementia.

PMID- 9251081
TI  - Myoclonus in corticobasal degeneration.
AB  - Five patients with unilateral myoclonus and a clinical diagnosis of corticobasal
      degeneration (CBD) were studied. All patients showed enhanced long-loop responses
      in their myoclonic arms without enlarged somatosensory potentials. The cortical
      relay time of the long-loop responses was studied in three patients, in two of
      whom it was < 2 ms, even in the nonmyoclonic arm. Myoclonus in CBD is probably
      related to an enhanced long-loop reflex whose pathway is unlikely to be the same
      as that in classic cortical reflex myoclonus.

PMID- 9251082
TI  - Cerebellar hypermetria: reduction in the early component of the antagonist
      electromyogram.
AB  - Several articles have described the electromyographic (EMG) patterns underlying
      cerebellar hypermetria. However, the description of the EMG associated with
      hypermetria is not consistent between studies. It is hypothesized that the reason
      for this concerns the criteria used to define and describe the antagonist
      latency. Several studies on neurologically normal individuals have shown that
      there are two components to the antagonist EMG: an early component and a late
      component. However, many studies have identified only one component and have not
      defined whether it was the early or late component. A reanalysis of one published
      data set that had previously identified only one antagonist component was
      performed. The reanalysis suggests that hypermetria can be caused by an absence
      of an early antagonist EMG component, a delayed late component, or both. In
      addition, a new measure is suggested that allows this hypothesis to be further
      evaluated.

PMID- 9251083
TI  - Gabapentin and motor fluctuations in Parkinson's disease.

PMID- 9251084
TI  - The stability of carbidopa in solution.

PMID- 9251086
TI  - Reversible parkinsonism, hypophosphoremia, and hypocalcemia under vitamin D
      therapy.

PMID- 9251085
TI  - Risperidone in levodopa-induced psychosis in advanced Parkinson's disease: an
      open-label, long-term study.

PMID- 9251087
TI  - Correlation between results of motor section of UPDRS and Webster Scale.

PMID- 9251088
TI  - Machado-Joseph disease/spinocerebellar ataxia 3 responsive to buspirone.

PMID- 9251089
TI  - Stereotypies in Wilson's disease.

PMID- 9251090
TI  - Neurological manifestations in two related xeroderma pigmentosum group D
      patients: complications of the late-onset type of the juvenile form.

PMID- 9251091
TI  - Episodic undulating hyperkinesias of the tongue associated with brainstem
      ischemia.

PMID- 9251092
TI  - Imipenem-induced myoclonus.

PMID- 9251093
TI  - Acute reversible myoclonic encephalopathy associated with fluoxetine therapy.

PMID- 9251094
TI  - Fluoxetine-induced movement disorders and deficient CYP2D6 enzyme activity.

PMID- 9251095
TI  - Stability of levodopa/carbidopa solutions.

PMID- 9251096
TI  - Oculofacial-skeletal myorhythmia in Whipple's disease.

PMID- 9251097
TI  - Modulation of potassium-evoked [3H]dopamine release from rat striatal slices by
      voltage-activated calcium channel ligands: effects of omega-conotoxin-MVIIC.
AB  - We examined the involvement of voltage-activated Ca2+ channels (VACCs) on K+(50
      mM)-evoked [3H]dopamine ([3H]DA) release from superfused rat striatal slices.
      Neither nifedipine nor nitrendipine modified K(+)-evoked [3H]DA release,
      indicating that L-type VACCs are not involved. K(+)-evoked [3H]DA release was
      partially inhibited by omega-CTx-GVIA and omega-Aga-IVA, and was abolished by 3
      microM omega-CTx-MVIIC (IC50 approximately 128 nM), suggesting the involvement of
      N-, P-, or Q-type VACCs, respectively. Moreover, even subnanomolar concentrations
      of omega-CTx-MVIIC (0.1-0.5 nM) inhibited K(+)-evoked [3H]DA release by
      approximately 25%, suggesting the possible involvement of a still not classified
      (perhaps O-type?) Ca2+ channel subtype. The effects of omega-CTx-MVIIC (10-100
      nM) and omega-CTx-GVIA (1 microM) were additive, suggesting that low nanomolar
      concentrations of omega-CTx-MVIIC does not interact with N-type VACCs. In
      conclusion, the K(+)-evoked [3H]DA release from rat striatal slices is mediated
      by entry of Ca2+ through omega-CTx-GVIA sensitive (N-type) as well as through
      omega-Aga-IVA (P-type) and omega-CTx-MVIIC (probably Q-type) sensitive VACCs.

PMID- 9251098
TI  - Imipramine-induced changes in 5-HT2 receptor sites and inositoltrisphosphate
      levels in rat brain.
AB  - The effect of chronic administration of Imipramine on [3H]Spiperone binding to 5
      HT2 sites and inositoltrisphosphate (IP3) levels in rat cerebral cortex was
      studied. Our data shows that treatment with imipramine (5 mg/kg body weight,
      intraperitoneally) for 30 days significantly down regulates 5-HT2 receptors sites
      (262 +/- 29 fmol/mg protein) in cerebral cortex (38%), compared to control rats
      (425 +/- 60 fmol/mg protein., P < 0.001). However there was no significant change
      in the affinity of [3H]-Spiperone binding (kd) to 5-HT2 sites in cerebral cortex
      after exposure to imipramine (Kd = 0.84 +/- 0.11 nM). It is also observed that
      imipramine treatment significantly reduces 5-HT stimulated [3H]IP3 formation in
      cerebral cortex (6,411 +/- 708 dpm/mg protein), compared to the saline treated
      rats (12,238 +/- 1,544 dpm/mg protein; P < 0.001), with concomitant decrease in
      Pdtlns-4-5-P2. This study suggests that the therapeutic action of imipramine in
      brain might be by reducing hypersensitivity of 5-HT2 receptors by down
      regulation, which leads to reduced levels of inositolphospholipids. This inturn
      reduces the levels of IP3. In conclusion, imipramine acts at presynaptic site by
      blocking the reuptake of serotonin and at post synaptic site it downregulates 5
      HT2 sites with decreased IP3 levels after chronic exposure.

PMID- 9251099
TI  - Benzodiazepine prevention of swim stress-induced sensitization of cortical
      biogenic amines: an in vivo microdialysis study.
AB  - In vivo microdialysis was used to determine the effect of diazepam, flumazenil
      and FG-7142 upon the biogenic amine response to acute and repeated swim stress in
      the medial prefrontal cortex of the rat. Acute swim stress increased
      norepinephrine levels, although dopamine and serotonin levels remained stable.
      Upon re-exposure to swim stress twenty-four hours later, sustained increases (200
      300% of baseline) in all three biogenic amines were detected. This enhanced
      response to re-stress was not seen in rats pretreated with either a
      benzodiazepine: agonist (diazepam, 2 mg/kg), an antagonist (flumazenil, 10
      mg/kg), or an inverse agonist (FG-7142, 10 mg/kg) given prior to the first swim
      stress. Therefore, the sensitization of biogenic amine response to re-stress may
      be prevented by compounds which differ in their activity at the benzodiazepine
      receptor.

PMID- 9251100
TI  - Sigma 1 receptor subtype is involved in the facilitation of cortical dopaminergic
      transmission in the rat brain.
AB  - Our previous studies have shown that three sigma (sigma) receptor ligands, (+)-N
      allylnormetazocine ((+)-SKF-10,047), (+/-)-pentazocine and 1,3-di(2
      tolyl)guanidine (DTG) differently regulated the dopamine (DA) transmission in the
      rat brain. In the present study, we attempted to clarify the role of sigma 1
      receptor subtype in the regulation of DA transmission using a novel and selective
      sigma 1 receptor agonist, 1-(3,4-dimethoxyphenethyl)-4(3-phenylpropyl)piperazine
      dihydrochloride (SA4503) in the rat brain. Acute administration of SA4503 (1.0
      mg/kg, p.o.) significantly increased DA and 3,4-dihydroxyphenylacetic acid
      (DOPAC) levels in the rat frontal cortex, but not in the other six regions,
      hippocampus, striatum, midbrain, cerebellum, medulla/pons and hypothalamus. The
      increase of cortical DA level elicited by SA4503 was fully reversed by N,N
      dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) (0.25 mg/kg,
      p.o.), a putative sigma 1 receptor antagonist. In addition, SA4503 (1.0 mg/kg,
      p.o.) showed an increase of cortical L-3,4-dihydroxyphenylalanine (L-DOPA)
      accumulation under the inhibition of dopa decarboxylase activity with m
      hydrobenzylhydrazine (NSD-1015), suggesting that SA4503 has activated the
      cortical DA synthesis rate. These results suggest that the sigma 1 receptor
      subtype plays an important role in the facilitation of cortical DA transmission.
      In addition, this phenomenon is partially involved in the augmentation of DA
      synthesis rate.

PMID- 9251101
TI  - Effect of hemorrhagic hypotension on cortical oxygen pressure and striatal
      extracellular dopamine in cat brain.
AB  - This study investigated the relationships between blood pressure, cortical oxygen
      pressure, and extracellular striatal dopamine in the brain of adult cats during
      hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the
      cortex was measured by the oxygen dependent quenching of phosphorescence and
      extracellular dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA) by in vivo microdialysis. Following a 2 h stabilization period after
      implantation of the microdialysis probe in the striatum, the mean arterial blood
      pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control)
      to 90 Torr, 70 Torr and 50 Torr, holding the pressure at each level for 15 min.
      The whole blood was then retransfused and measurements were continued for 90 min.
      As the MAP was lowered there was a decrease in arterial pH, from a control value
      of 7.37 +/- 0.05 to 7.26 +/- 0.06. The PaCO2 decreased during bleeding from 32.3
      +/- 4.8 Torr to 19.6 +/- 3.6 Torr and returned to 30.9 +/- 3.9 Torr after
      retransfusion. The PaO2 was 125.9 +/- 15 Torr during control conditions and did
      not significantly change during bleeding. Cortical oxygen pressure decreased with
      decrease in MAP, from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and
      22 +/- 2 Torr, respectively. A statistically significant increase in striatal
      extracellular dopamine, to 2,580 +/- 714% of control was observed when MAP
      decreased to below 70 Torr and cortical oxygen pressure decreased to below 31
      Torr. When the MAP reached 50 Torr, the concentration of extracellular dopamine
      increased to 18,359 +/- 2,764% of the control value. A statistically significant
      decrease in DOPAC and HVA were observed during the last step of bleeding. The
      data show that decreases in systemic blood pressure result in decrease in oxygen
      pressure in the microvasculature of the cortex, suggesting vascular dilation is
      not sufficient to result in a full compensation for the decreased MAP. The
      decrease in cortical oxygen pressure to below 32 Torr is accompanied by a marked
      increase in extracellular dopamine in the striatum, indicating that even such
      mild hypoxia can induce significant disturbance in brain metabolism.

PMID- 9251102
TI  - Developmental lead exposure and two-way active avoidance training alter the
      distribution of protein kinase C activity in the rat hippocampus.
AB  - Long-term exposure to a low level of lead is associated with learning deficits.
      Several types of learning have been correlated to hippocampal protein kinase C
      (PKC) activation. This study was designed to determine if there is a correlation
      between the effects of lead on hippocampal PKC activation and those on learning
      performance. Rats were exposed to 0.2% (w/v) lead acetate at different
      developmental stages including a maternally exposed group, a postweaning exposed
      group, and a continuously exposed group. The continuously lead exposed rats
      tended to avoid less frequently and not respond more frequently in two-way active
      avoidance training than did controls. This training process was associated with
      translocation of hippocampal PKC activity from cytosol to membrane. Two-way
      analysis of variance of data indicates that there is a significant training and
      lead treatment interaction in the ratio of membrane to cytosolic PKC activity
      (F3,32 = 3.013; p = 0.044). The interaction is attributable to the absence of the
      training-induced PKC translocation in the continuously lead exposed rats. In
      addition, no significant changes were observed in learning performance and
      training-induced hippocampal PKC activation after maternal and postweaning lead
      exposure. Continuous and longer duration of lead exposure appears to affect the
      learning performance and hippocampal PKC activation. These data suggest that a
      change in the activation of hippocampal PKC may be involved in the lead-induced
      deficit in learning.

PMID- 9251103
TI  - Metabotropic glutamate receptor expression in cultured rat astrocytes and human
      gliomas.
AB  - In order to confirm the existence of metabotropic glutamate receptors in
      astroglial cultures and to provide information on different receptor subtypes,
      the expression of different mGluRs was analysed in cultures highly enriched in
      rat astroglial cells. mRNA levels for mGluR1, 2, 3, 4, 7 were undetectable by
      Northern blot analysis in primary type-1 astroglial cultures derived from total
      cerebral hemispheres, cerebral cortex and striatum. Interestingly, these cultures
      expressed a low, but detectable, level of mGluR5 mRNA. The more sensitive
      technique Reverse Transcription-Polymerase Chain Reaction (RT-PCR) confirmed the
      presence of mGluR5 transcript in cultured astrocytes and, in addition, revealed
      the presence of mGluR3 mRNA. The lack of expression of mGluR5 in CG-4 cells, a
      rat cell line able to differentiate in type-2 astrocytes or oligodendrocytes
      depending on the culture conditions, suggested that the presence of mGluR5 was
      not a general feature of cells of glial origin. Moreover, all the examined mGluR
      transcript were undetectable by RT-PCR in CG4 cells. In order to confirm the
      possible expression of mGluR5 in cell of glial origin we examined the mRNA levels
      for this receptor in tissue samples from human gliomas obtained after surgical
      resection of the tumors: only 1 sample (grade II astrocytoma), out of 8 examined,
      showed the presence of mGluR5 mRNA. In conclusion our data show that the only
      cloned metabotropic receptor linked to phosphoinositide hydrolysis, whose
      expression is detectable in cultured type-1 astrocytes, in mGluR5. It remains to
      be established if the low level of expression of mGluR3 could be responsible for
      the group II metabotropic glutamate receptor activity previously observed in
      cultured astroglial cells.

PMID- 9251104
TI  - Is hypothalamic GABA involved in immune function in relation to dietary protein
      during aging?
AB  - Hypothalamic GABAergic activity and immune response in spleen were not
      significantly changed with the increase of age from 3 to 6 months in adult male
      albino rats. Further increase of age from 6 to 9 months increase the GABAergic
      activity and decreased the cell viability in spleen without any change in its T
      lymphocyte cytotoxicity. Consumption of low protein diet (LPD) for a short-term
      period (STP; 7 consecutive days) increased the hypothalamic GABAergic activity
      without changing the immune response in 3 months old rats. When supplemented for
      a long-term period (LTP; 30 consecutive days) to 3 months old rats, a reduction
      of hypothalamic GABAergic activity and the immune response was observed. Intake
      of high protein diet (HPD) for both STP and LTP increased the GABAergic activity
      and immune response, but the increase of GABAergic activity in hypothalamus under
      STP was greater than that observed under LTP. In 6 months old rats consumption of
      LPD for STP reduced the GABAergic activity without any alteration of its immune
      response. Long-term supplementation of this LPD to the same age group increased
      GABAergic activity and the mitotic activity of spleen cells without any
      alteration of the functional activity of the T-cells in spleen. Consumption of
      HPD for STP failed to produce any change in hypothalamic GABAergic activity and
      the immune response of 6 months old rats. Supplementation of HPD for LTP reduced
      the hypothalamic GABAergic activity and the immune response of the same age
      group. The reduction in hypothalamic GABAergic activity without any change in the
      immune response was observed following the supplementation of low protein diet to
      9 months old rat for STP. Intake of the LPD for LTP also reduced the hypothalamic
      GABAergic activity and the mitotic activity of the spleen cells without any
      alteration of the functional activity of the T-cells in spleen of 9 months old
      rats. Supplementation of HPD for STP to this aged rat, on the other hand, failed
      to produced any change in hypothalamic GABAergic activity and the immune
      response. Intake of HPD for LTP by this aged rats increased the hypothalamic
      GABAergic activity along with the immune response. The results of this study,
      thus, suggest that hypothalamic GABAergic activity during aging is an index of
      immune response and it is modulated following the short- and long-term
      consumption of protein poor and protein rich diet.

PMID- 9251106
TI  - Ca(2+)-independent autophosphorylation of postsynaptic density-associated
      Ca2+/calmodulin-dependent protein kinase.
AB  - A major protein in the postsynaptic density fraction is alpha-CAM kinase II, the
      alpha-subunit of the Ca2+/calmodulin-dependent protein kinase.
      Autophosphorylation of the postsynaptic density-associated CaM kinase II is
      likely to be a crucial event in the induction of activity-dependent synaptic
      modification. This study focuses on the regulation and consequences of Ca(2+)
      independent autophosphorylation of the enzyme. In isolated postsynaptic
      densities, a sub-stochiometric level of autophosphorylation in the presence of
      Ca2+ is sufficient to trigger maximal Ca(2+)-independent autophosphorylation of
      alpha-CaM Kinase II. A major fraction of the sites phosphorylated in the absence
      of Ca2+ can be dephosphorylated by the endogenous phosphatase activity in the
      preparation. Ca(2+)-independent autophosphorylation is correlated with a drastic
      decrease in calmodulin binding to postsynaptic densities. This may represent a
      physiological mechanism that lower the calmodulin trapping capacity of the
      organelle, thus increasing the availability of calmodulin to other elements
      within a spine.

PMID- 9251105
TI  - Ornithine decarboxylase activity in cerebral post-ischemic reperfusion damage:
      effect of methionine sulfoximine.
AB  - Excessive activation of glutamate receptors via the N-methyl-D-aspartate (NMDA)
      subtype appears to play a role in the sequence of cellular events which lead to
      irreversible ischemic damage to neurons. Furthermore, NMDA receptor activation
      induces a stimulation of ornithine decarboxylase (ODC), the rate-limiting enzyme
      for polyamine (PA) biosynthesis. In order to better understand the role of PA we
      have measured ODC activity and the effect of methionine sulfoximine (MSO), a
      molecule able to stimulate ODC, on a model of transient cerebral ischemia. There
      was a significant increase in ODC activity in the rat cerebral cortex during post
      ischemic reperfusion. The treatment with MSO induced a significant decrease in
      cerebral glutamine synthetase activity accompanied by a marked increase in ODC
      activity. In MSO-pretreated rats there was a significant decrease in the survival
      rate when compared to untreated ischemic rats.

PMID- 9251107
TI  - Effect of alpha-ketoisocaproate and leucine on the in vivo oxidation of glutamate
      and glutamine in the rat brain.
AB  - Leucine and alpha-ketoisocaproate (alpha-KIC) were perfused at increasing
      concentrations into rat brain hippocampus by microdialysis to mimic the
      conditions of maple syrup urine disease. The effects of elevated leucine or alpha
      KIC on the oxidation of L-[U-14C]glutamate and L-[U-14C]glutamine in the brain
      were determined in the non-anesthetized rat. 14CO2 generated by the metabolic
      oxidation of [14C]glutamate and [14C]glutamine in brain was measured following
      its diffusion into the eluant during the microdialysis. Leucine and alpha-KIC
      exhibited differential effects on 14CO2 generation from radioactive glutamate on
      glutamine. Infusion of 0.5 mM alpha-KIC increased [14C]glutamate oxidation
      approximately 2-fold; higher concentrations of alpha-KIC did not further
      stimulate [14C]glutamate oxidation. The enhanced oxidation of [14C]glutamate may
      be attributed to the function of alpha-KIC as a nitrogen acceptor from
      [14C]glutamate yielding [14C]alpha-ketoglutarate, an intermediate of the
      tricarboxylic acid cycle. [14C]glutamine oxidation was not stimulated as much as
      [14C]glutamate oxidation and only increased at 10 mM alpha-KIC reflecting the
      extra metabolic step required for its oxidative metabolism. In contrast, leucine
      had no effect on the oxidation of either [14C]glutamate or [14C]glutamine. In
      maple syrup urine disease elevated alpha-KIC may play a significant role in
      altered energy metabolism in brain while leucine may contribute to clinical
      manifestations of this disease in other ways.

PMID- 9251110
TI  - A method to extract three-dimensional objects from three-dimensional NMR image
      data.
AB  - A method to extract shapes of bubble polyhedra from three-dimensional nuclear
      magnetic resonance image data of foam has been developed. The method consists of
      four steps: first, to compute series of maximum intensity projection images from
      the three-dimensional NMR image data of foam to visualize the network structure
      of the bubble edges; second, to measure the three-dimensional coordinates of
      vertices of the bubble polyhedra interactively on a CRT using the series of MIP
      images to obtain polyhedral edges; third, to construct polyhedral faces from the
      assembly of the edge data; and fourth, to construct bubble polyhedra from the
      assembly of the face data. The algorithm for construction of polygons and
      polyhedra is based on the selection of polygons or polyhedra from an enormous
      number of possible combinations of edges or faces under some simple selection
      rules. Since the computation time for the selection increased exponentially with
      the number of the edge data, a 'partial volume sweeping' method in which a cubic
      region which could accommodate any bubble polyhedron was swept over the three
      dimensional image area, was developed to reduce the computation time. By using
      this method, it was demonstrated that the shapes of many bubble polyhedra could
      be extracted automatically from the assembly of the edge data within a practical
      computation time.

PMID- 9251109
TI  - Absolute concentrations of metabolites in human brain tumors using in vitro
      proton magnetic resonance spectroscopy.
AB  - Water-soluble metabolites extracted from 60 surgically excised samples of various
      brain tumors and four nontumorous lobectomized brains were measured
      quantitatively using in vitro high-resolution magnetic resonance spectroscopy. A
      detailed MR spectrum-histology correlation study in a glioblastoma was made, to
      reveal MR spectral changes in accordance with the density of glioma cells.
      Furthermore, three cases that had difficult preoperative diagnoses are discussed.
      MR spectra from gliomas exhibited characteristic patterns according to
      malignancy, presumably reflecting its metabolic effects. Concentrations of
      choline-containing compounds, inositol, alanine, glycine and
      phosphorylethanolamine (PEA) increased according to the degree of malignancy, but
      it was noteworthy that in glioblastoma the choline-containing compounds,
      inositol, alanine, glycine and phosphorylethanolamine increased according to the
      degree of malignancy. In particular, the glycine concentration was very high in
      glioblastoma. We also detected a large amount of taurine in medulloblastoma.
      Although the total creatine concentrations decreased according to the malignancy,
      the concentration of total creatine was relatively preserved in neuroectodermal
      tumors but was low in nonneuroectodermal tumors. N-acetyl-aspartate was
      unequivocally demonstrated in normal tissues, but could not be detected in
      nonneuroectodermal brain tumors such as metastatic brain tumor, meningioma,
      neurinoma and chordoma. In meningioma, although a high peak of choline-containing
      compounds has been reported uniquely by in vitro and in vivo 1H-MRS, we
      demonstrated that its concentration was not increased in meningioma; instead,
      there was an increased alanine content. 1H-MRS of neurinoma demonstrated high
      inositol peaks, and a large amount of inositol. The reason for the high inositol
      content in neurinoma is unknown, but the prominent peak of inositol on MR spectra
      should be useful for the differential diagnosis of neurinoma from meningioma. PEA
      concentration was increased four to five times in pituitary adenoma, malignant
      lymphoma, and medulloblastoma as compared with normal brain. Thus 1H-MRS might
      provide clinically useful information on tumor malignancy and characteristic
      tumor metabolism. Although excellent anatomical information of tumors can be
      readily obtained by magnetic resonance imaging. MRS provides metabolic
      information. MRS may provide additional information in cases in which the
      differential diagnosis of tumors by neuroimaging is difficult.

PMID- 9251108
TI  - Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and
      2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors.
AB  - A study was made of the effects of reduced (GSH) and oxidized (GSSG) glutathione
      on the Na(+)-independent and N-methyl-D-aspartate (NMDA) displaceable bindings of
      glutamate, on the binding of kainate, 2-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA), and ligand of the brain NMDA receptor-ionophore
      complex: glycine, dizocilpine (MK-801) and (+/-)-3-(2-carboxypiperazin-4
      yl)propyl-1-phosphonate (CPP). GSH and GSSG strongly inhibited the binding of
      glutamate, CPP and AMPA, kainate and glycine binding being less affected. Both
      peptides enhanced the binding of dizocilpine in a time- and concentration
      dependent manner. This activatory effect was not additive to that of saturating
      concentrations of glutamate or glutamate plus glycine. The activation of
      dizocilpine binding by GSH and GSSG was prevented by the competitive NMDA and
      glycine antagonists DL-2-amino-5-phosphonovalerate and 7-chlorokynurenate. GSH
      and GSSG may be endogenous ligands of AMPA and NMDA receptors, binding preferably
      to the glutamate recognition site via their gamma-glutamyl moieties. In addition
      to this, at millimolar concentrations they may regulate the redox state of the
      NMDA receptor-ionophore complex.

PMID- 9251111
TI  - Relationship between gluconeogenesis and phosphoenergetics in rat liver assessed
      by in vivo 13C and 31P NMR spectroscopy.
AB  - The relationship between the phosphoenergetic state and gluconeogenesis in the
      liver after ischemic damage was investigated using living rats. The ATP level was
      determined with in vivo 31P nuclear magnetic resonance spectroscopy, and
      gluconeogenesis was evaluated with in vivo 31C NMR spectroscopy using L-[3
      13C]alanine as a tracer. These two measurements were alternated repeatedly. The
      rats were divided into three groups: without ischemia (group A); with 10 min
      ischemia (group B); and with 30 min ischemia (group C). ATP was depleted to 20%
      of the preischemic state after 10 min ischemia and this level was maintained
      during 30 min ischemia. After reperfusion, the ATP level was partially restored,
      but the recovery was smaller in group C. Infusion of [3-13C]alanine was started
      immediately after the reperfusion. In vivo 13C NMR disclosed changes in the
      alanine C3, glutamine/glutamate C2 and C3, glucose C1-6, and glycogen C1 signals
      in the liver. After 60 min infusion of [3-13C]alanine, the ATP level correlated
      negatively with the signal intensity of alanine (r = -0.664, p = 0.008) and
      positively with those of glucose and glyogen (r = 0.586, p = 0.023, and r =
      0.643, p = 0.011, respectively). These results suggest that the ATP level
      participates in gluconeogenesis and glycogenesis in the liver. Such multinuclear
      in vivo NMR observations might uncover new aspects of the metabolic function of
      the liver in the in vivo state.

PMID- 9251112
TI  - Evaluation of metabolic heterogeneity in brain tumors using 1H-chemical shift
      imaging method.
AB  - Seventeen brain tumors were measured by 1H-CSI (chemical shift imaging) in a 1.5
      T clinical magnetic resonance scanner. The metabolic peaks obtained were
      evaluated by two methods. One method was to obtain the percentage of each
      metabolite relative to the combined choline, creatine and NAA peak areas, and the
      other method was to obtain a ratio of the tumor to contralateral brain. The
      percentage of choline (%Cho) and choline ratio increased, and the %NAA and NAA
      ratio decreased in the gliomas and malignant tumors. In relation to grading, %Cho
      increased but the choline ratio did not. We believed the reason for this was that
      there were many foci of microscopic necrosis in the glioma grade IV. Free lipids
      were observed in most of the high grade gliomas and in a malignant tumor. Lactate
      increased in higher grade tumors. Meningiomas showed the highest %Cho.
      Statistical differences between the grades of glioma were not detected because
      many tumors had heterogeneous tissue. One resolution to this problem was
      metabolite mapping. Mapping of the percentage of metabolites was suitable because
      it described the regional metabolic changes and the resulting signal to noise
      ratio was better than that achieved by other methods of evaluation.

PMID- 9251113
TI  - Micro-magnetic resonance imaging of the inner ear in the guinea pig.
AB  - We applied a magnetic resonance microscopy at 7.05 T with a gradient coil unit to
      image the fine structure of the guinea pig cochlea. First, a three-dimensional MR
      image of the surface of the cochlea was obtained to select the location of cross
      sectional images. Then, cross-sectional images of the basal turn, the second turn
      and the apical turn of the cochlea were obtained. Based upon the different
      protein concentrations of the endolymph vs the perilymph, the scala vestibuli,
      scala tympani and the cochlear duct could be clearly distinguished. This allowed
      a determination of the location of both the basilar membrane and Reissner's
      membrane. We raise the possibility that MRM may become useful in the diagnosis of
      endolymphatic hydrops (Meniere's disease).

PMID- 9251115
TI  - Update on hepatic intra-arterial chemotherapy.
AB  - The use of hepatic intra-arterial (HIA) chemotherapy is based on the
      pharmacologic principle that the regional administration of certain drugs can
      lead to higher drug concentrations at the site of a tumor. This has been studied
      most extensively in patients with liver-only colorectal metastases. Four large
      randomized studies have failed to demonstrate a survival advantage of regional
      treatment over systemic chemotherapy, although two meta-analyses confirmed an
      improvement in response rate and suggest a trend toward improvement in survival.
      Two randomized studies have shown improved survival in patients treated with HIA
      chemotherapy, as compared with those given supportive care, and quality of life
      also appears to be superior in HIA chemotherapy recipients. The treatment
      employed in all of the randomized studies was hindered by substantial
      hepatobiliary toxicity and many surgical complications. Improved surgical
      techniques and newer chemotherapy combinations appear to have improved phase II
      results with HIA therapy, leading to a randomized trial now being conducted by
      the Cancer and Leukemia Group B (CALGB). The role of HIA chemotherapy in adjuvant
      settings and in other diseases has not been as well-studied, and such uses remain
      appropriate only for very selected patients. Ultimately, the regional advantage
      gained by the HIA route may prove to be most advantageous for the delivery of
      newer biologic agents.

PMID- 9251116
TI  - Coalition president urges policy board to focus on the policy and practices
      affecting cancer research.

PMID- 9251114
TI  - 19F NMR of 2-deoxy-2-fluoro-D-glucose for tumor diagnosis in mice. An NDP-bound
      hexose analog as a new NMR target for imaging.
AB  - A well-known radiopharmaceutical 2-deoxy-2-fluoro-D-glucose widely used for
      positron emission tomography diagnosis in terms of glucose utilization, was re
      evaluated here as a nuclear magnetic resonance pharmaceutical for cancer
      detection. The uptake and metabolism of FDG in the experimental tumor, MH134,
      transplanted to the peritoneum of C3H mice as an ascitic tumor was studied
      extensively by ex vivo 19F NMR. Prolonged retention of FDG and its metabolites
      over 2 days was confirmed in the tumor cells as well as in the heart. In these
      tissues, the 6-phosphate of the injected compound was converted reversibly to its
      epimer 2-deoxy-2-fluoro-D-mannose and further to their NDP bound forms. The
      metabolites were almost cleared within a day from the other healthy organs where
      the formation of NDP-2-deoxy-2-fluoro-D-mannose was low. Thus, the 19F NMR signal
      of NDP-FDM detected 1 day after the FDG injection could be used as a target
      signal for tumor detection. Through the use of in vivo 19F NMR spectra and 19F
      chemical shift images, the feasibility of this proposal was demonstrated. It was
      concluded that FDG-NMR has a potential for tumor diagnosis in animals.

PMID- 9251117
TI  - Role of diet in cancer hard to study, expert says.

PMID- 9251118
TI  - Recent progress in radioimmunotherapy for cancer.
AB  - Radioimmunotherapy allows for the delivery of systemically targeted radiation to
      areas of disease while relatively sparing normal tissues. Despite numerous
      challenges, considerable progress has been made in the application of
      radioimmunotherapy to a wide variety of human malignancies. The greatest
      successes have occurred in the treatment of hematologic malignancies.
      Radioimmunotherapy, with or without stem-cell transplant support, has produced
      substantial complete remission rates in chemotherapy-resistant B-cell lymphomas.
      Nonmyeloablative regimens have shown so much promise that they are now being
      tested as initial therapy for low-grade B-cell lymphomas. Although solid tumor
      malignancies have been less responsive to radioimmunotherapy, encouraging results
      have been obtained with locoregional routes of administrations, especially when
      the tumor burden is small. Greater tumor-to-normal tissue ratios are achievable
      with regional administration. Even with intraperitoneal and intrathecal
      administration, bone marrow suppression remains the dose-limiting toxicity.
      Ongoing research into new targeting molecules, improved chelation chemistry, and
      novel isotope utilization is likely to extend the applications of this strategy
      to other tumor types. The potential for radioimmunotherapy will be enhanced if
      this modality can be optimally adapted for integration with other agents and if
      the administration method can be tailored to the type and distribution of
      malignancy.

PMID- 9251119
TI  - Clinical trials referral resource. Clinical trials with pyrazoloacridine.

PMID- 9251120
TI  - Results of newer radiation treatments for prostate cancer.

PMID- 9251121
TI  - BMT for severe autoimmune diseases: an idea whose time has come.
AB  - Most patients with autoimmune diseases are thought to have a a normal life
      expectancy, and thus are treated conservatively. However, these diseases have a
      diverse clinical course. A small subset of patients have "severe autoimmune
      diseases," or SADS, which are rapidly progressive and are associated with early
      mortality. If patients with SADS can be identified before they develop
      irreversible organ damage, aggressive intervention would be indicated.
      Consequently, patients with SADS are now being enrolled in experimental protocols
      of immune ablation and hematopoietic stem-cell rescue (ie, bone marrow
      transplantation [BMT] at several US institutions. For various reasons, including
      the high cost of BMT, it will probably be years before the benefits, if any, of
      this procedure are known.

PMID- 9251123
TI  - New evidence that NSAIDs reduce breast cancer risk.

PMID- 9251122
TI  - Tumor Board Conference from the University of Pittsburgh.

PMID- 9251124
TI  - Colorectal cancer surgical practice guidelines. Colorectal Cancer Practice
      Guideline Committee.

PMID- 9251125
TI  - Esophageal cancer surgical practice guidelines. Esophageal Cancer Practice
      Guideline Committee.

PMID- 9251126
TI  - Gastric cancer surgical practice guidelines. Gastric Cancer Practice Guideline
      Committee.
AB  - The data described above suggest that the current management of gastric carcinoma
      requires a surgical resection. Identification of the number of lymph nodes that
      may be involved with cancer is an important prognosticator. Resection of involved
      lymph nodes is likely to decrease the morbidity of locoregional recurrence.
      However, this has not been adequately addressed in the studies performed to date.
      Nonetheless, accurate staging is an essential goal of the primary therapy of
      gastric carcinoma. The limits of resection for a gastric cancer are outlined in
      the guidelines (see page 1068). Administration of adjuvant therapy, such as
      chemotherapy or radiation therapy, remains controversial and is the subject of
      ongoing clinical research. Until a prospective, randomized trial demonstrates a
      significant improvement in survival, there remains little or no basis for the
      addition of adjuvant therapy outside the context of a clinical trial.

PMID- 9251127
TI  - Pancreatic cancer surgical practice guidelines. Pancreatic Cancer Practice
      Guideline Committee.

PMID- 9251128
TI  - Breeding and genetics--historical perspective.
AB  - This paper is a review of selection methods that have been used in commercial
      breeding of table egg stocks, broilers, and turkeys, based on the author's
      experience. In addition, a number of historic developments that have shaped or
      influenced the selection process are listed and the significance of each is
      discussed. The merits of mass selection are noted and compared with the multiple
      forms of family selection, e.g., full or half sibs, progeny testing, and
      recurrent methods. Each of these methods is believed to have nearly universal
      application in applied breeding programs being practiced today. This review
      concludes that a combination of individual and family selection practices aimed
      at improving multiple traits simultaneously is required to remain a successful
      supplier of breeding stock to the current commercial industry.

PMID- 9251129
TI  - Genetic selection strategies--population genetics.
AB  - This paper provides an overview of the association between population genetics
      and selection strategies in poultry. Relationships between artificial and natural
      selection and among causes contributing to limits to artificial selection are
      discussed. Homeostasis and resource allocations at the individual and at the
      population level are reviewed. Examples from poultry demonstrate where human
      intervention has circumvented biological limits. Lastly, this paper considers the
      role of population genetics in future breeding strategies for poultry.

PMID- 9251130
TI  - Genetic selection strategies: computer modeling.
AB  - There are four primary factors to consider in genetic selection strategies: 1)
      accuracy of selection, 2) selection intensity, 3) effective population size, and
      4) mating system. Current theory indicates that optimum response to selection is
      achieved by maximizing the first three factors and using a mating systems that
      allows optimization of reproductive characteristics in dam lines and production
      characteristics in sire lines. However, with limited resources, compromises among
      the first three factors are needed. Simulations are useful for examining those
      compromises. Unrealistic simplifying assumptions are necessary for analytic
      theoretical results and thus do not address real world breeding problems. Using
      simulations, the relationship between selection accuracy, which is increased by
      use of family selection indices or Best Linear Unbiased Prediction (BLUP), and
      response to selection was examined. Results show that those procedures place a
      great restriction on effective population size, which offsets most of their
      advantage, i.e., there is too little emphasis on effective population size. A
      revision of the methodology and a reappraisal of the results of selection theory
      for optimization of genetic response is required. Another relationship that is of
      fundamental importance in breeding programs is that between selection intensity
      and effective population size. Analytical results for the additive case have been
      developed but have never been extended to heterotic traits. A gene level
      simulation program was developed to examine that relationship. Results show that
      the optimal selection strategy depends on the trait being selected. For additive
      traits and in the short term (20 generations), one should maximize selection
      intensity. For heterotic traits, an intermediate proportion (25% of each sex)
      gives optimal response. In all breeding strategies, primary attention must be
      given to the rate of inbreeding, which is increased by increasing either accuracy
      of selection or selection intensity. Inbreeding reduces response to selection in
      two ways. First, for both additive and nonadditive traits, inbreeding is a
      measure of the amount of random genetic drift that has occurred. Genetic drift
      causes loss of favorable alleles. Once lost, those alleles can never be recovered
      and thus genetic drift lowers the selection limit. Second, for heterotic traits,
      inbreeding results in a depression of the mean caused by directional dominance.

PMID- 9251131
TI  - Strategies for the future.
AB  - The current advances in molecular genetics and gene transfer are introduced
      together with the existing international research programs on these technologies.
      The opportunities for exploitation are discussed and how they could be
      incorporated into current breeding programs. Finally, issues of public concern
      and acceptability are raised and put into the context of existing breeding
      schemes and regulations.

PMID- 9251132
TI  - Manipulation of blastodermal cells.
AB  - Blastodermal cells isolated from newly laid, unincubated eggs are virtually
      uncommitted cells that exhibit many of the properties of pluripotential stem
      cells. They can be transferred from donor to recipient embryos and contribute to
      both somatic tissues and the germline. Blastodermal cells that have been
      maintained in culture for 7 d express the epitopes ECMA-7 and SSEA-1, which are
      also expressed by mouse embryonic stem cells. After culture for up to at least 7
      d, blastodermal cells retain the ability to differentiate into somatic tissues
      and the germline both in vivo and in vitro. Proliferation in the absence of
      differentiation of blastodermal cells is stimulated by the presence of Leukemia
      Inhibitory Factor (LIF) and other ligands that interact with the gp130 receptor,
      and differentiation is stimulated by exposure to retinoic acid. Blastodermal
      cells also possess high levels of telomerase activity, which is shared by
      immortalized cells and cells within the germline. Blastodermal cells can be
      transfected and will express foreign genes both in vivo and in vitro. Transfected
      cells can be isolated by fluorescence activated cell sorting and can be
      cryopreserved without losing their ability to contribute to either somatic
      tissues or the germline. These properties of blastodermal cells make them ideal
      vectors for introducing genetic modifications to the germline.

PMID- 9251134
TI  - Embryo manipulation of the germplasm.
AB  - The development of the avian embryo is used to demonstrate the potential for
      future advances in genomic strategies. A mathematical model is derived to
      indicate the most useful approaches for using chimeras to access the chicken
      genome. A review of the way that germ cells are processed through the gonad
      highlights the need for such an analysis of cell kinetics and indicates that the
      right rudimentary gonad may also be a useful area for research into germ cell and
      stroma signalling. Studies on the B cells of the immunological system show that
      antibody diversity is achieved by gene splicing and that these cells are capable
      of inducing homologous recombination in a wide range of chromosomes. This
      property opens up a whole strategy for chromosome manipulation that may be
      particularly useful in exploiting the properties of the avian microchromosome
      system.

PMID- 9251133
TI  - The origin of the avian germ line and transgenesis in birds.
AB  - The origin of the germ cell lineage in vertebrates is a fundamental question that
      has preoccupied developmental biologists. Recent work on the origin of the avian
      germ line has extended and clarified our understanding of the temporal and
      spatial segregation of primordial germ cells (PGC) during prestreak stages of
      development. The germ cells first appear at Stage X (Eyal-Giladi and Kochav,
      1976) in the ventral surface of the area pellucida in a scattered pattern among
      polyingressing cells. Subsequently, the PGC gradually translocate from the
      epiblast to the hypoblast. The entire process appears to be dependent upon the
      maintenance of an organized area pellucida. Little is known about the regulatory
      events governing germ cell emergence during this period; however, the culture of
      dispersed blastodermal cells on a mouse fibroblast feeder layer can compensate
      for a disorganized area pellucida and offers an in vitro system to examine the
      molecular basis of germ cell development. Such basic information is valuable for
      current approaches towards the production of transgenic poultry with targeted
      changes to the genome through the use of avian embryonic stem cells or primordial
      germ cells. Refinement of the culture of primordial germ cells or their
      precursors should allow academic and industrial research laboratories to answer
      significant biological questions and to improve the genetic potential of
      commercial poultry stocks. A better understanding of the biology of avian
      primordial germ cells during early embryo development can only enhance this
      process.

PMID- 9251135
TI  - Mapping the chicken genome.
AB  - Most economically important traits are genetically complex and controlled by
      numerous genes. A quality genetic map is a prerequisite for identifying
      quantitative trait loci (QTL) that contain the genes involved in these traits.
      Currently, there are two internationally recognized reference families that are
      used to build genetic maps. In this paper, the East Lansing (EL) genetic map is
      described in detail. Presently, the EL genetic map contains 617 genetic markers,
      of which 589 are resolved into 41 linkage groups. The map coverage within linkage
      groups is over 2,700 cM, which is about the estimated size of the chicken genome.
      There are 322 microsatellite markers, which greatly enhances the utility of this
      genetic map for genome-wide QTL searches. Also, 101 genes have been mapped, which
      will aid in the development of a comparative map. Further efforts to improve the
      genetic map and the potential for the map to identify QTL are discussed.

PMID- 9251136
TI  - DNA marker technology: a revolution in animal genetics.
AB  - The development of DNA-based markers has had a revolutionary impact on gene
      mapping and, more generally, on all of animal and plant genetics. With DNA-based
      markers, it is theoretically possible to exploit the entire diversity in DNA
      sequence that exists in any cross. For this reason, high resolution genetic maps
      are being developed at an unprecedented speed. The most commonly used DNA-based
      markers include those based on a cloned and (usually) sequenced DNA fragment and
      other, more random, assays for genetic polymorphism that can be grouped under the
      heading of fingerprint markers. The advantages and disadvantages of the various
      marker types are discussed, along with their application to the reference chicken
      genetic linkage maps and to the search for quantitative trait loci (QTL). The
      prospects for the use of DNA-based markers in marker-assisted selection are
      considered, along with likely future trends in poultry gene mapping. Further
      development of both physical and linkage genome maps of the chicken will allow
      animal scientists to more efficiently detect and characterize QTL and will
      provide them access to the wealth of genetic information that is being generated
      about the human genome and the genomes of model species, such as the mouse and
      Drosophila.

PMID- 9251137
TI  - Map-based quantitative trait locus identification.
AB  - Poultry gene mappers chose microsatellites as the main source of genetic markers
      for poultry genome mapping, similar to the marker type used for other farm
      animals, laboratory animals, and humans. Optimal strategies for applying DNA
      markers in poultry populations are discussed, including the number of markers to
      be used, genome representation, population structure, choice of markers,
      population size, statistical stringency for association between markers and
      quantitative trait loci (QTL), and biological verification of a linkage. It is
      shown that an efficient strategy should be based on a combination of a low
      stringent statistical test for the existence of linkage between a marker and QTL
      and an appropriate genetic test for the discrimination between true and false
      linkage. The source of the genetic variation to be used is discussed and, as an
      illustration, three types of resource populations are presented. The
      informativeness of different matings using various genotypes of the parents are
      considered and it appears that selection of markers based on the heterozygosity
      of the sire is the most efficient marker screening approach.

PMID- 9251138
TI  - Commercial approaches to genetic selection for growth and feed conversion in
      domestic poultry.
AB  - Tremendous genetic progress has been observed historically for growth and feed
      conversion through the efforts of the primary breeding companies. However,
      significant between-strain variation still exists due to differences in selection
      emphasis and selection techniques practiced by these organizations. This paper
      provides an overview of methods currently employed in commercial poultry breeding
      with reference to factors complicating program design and future challenges
      facing the industry. Mass selection for body weight has resulted in a significant
      reduction in the number of days required to grow bird to market weight with
      indirect improvements in feed conversion. Direct selection for feed conversion is
      accomplished through part record testing of males that have been preselected for
      body weight, conformation, and defect traits. Data are commonly subjected to
      complex statistical analysis both to correct feed conversion for variation in
      body weight and to improve the accuracy of breeding value estimates. Feed
      conversion breeding values of male sibs are sometimes used for the selection of
      female candidates as well. Selection for growth rate and efficiency has resulted
      in negative complications, such as ascites, reduced reproductive performance,
      skeletal abnormalities, and increased carcass fatness. Some of these factors may
      be partially ameliorated through modified selection practices. If not addressed
      by the breeding industry, the disruption of physiological homeostasis might
      ultimately represent economic and genetic barriers to further progress in
      improving growth and efficiency. Modern techniques in molecular genetics,
      utilized in conjunction with traditional quantitative genetic approaches, will
      provide additional opportunities to circumvent these physiological complications
      associated with genetic selection for growth and feed efficiency.

PMID- 9251139
TI  - Integration of classical and molecular approaches of genetic selection: disease
      resistance--implications for selection.

PMID- 9251140
TI  - Integration of classical and molecular approaches of genetic selection: egg
      production.
AB  - Poultry breeding has demonstrated success from the use of a complex mixture of
      assessment tools. New proposals are regularly sought out and tested for their
      ability to translate data into information that enhances genetic gain from
      selection. Details long hidden from view are already being uncovered by molecular
      genetics, calling for great skill and discipline to discern and harness their
      real potential. Some aspects of egg production grudgingly may yield to the
      influence of new associations suggested from molecular work. In particular,
      diverse environments call for the kind of genetic variation found only under
      expensive multiple-location testing, longer flock production life calls for
      better early predictors, and new egg products call for novel measures of egg
      component value. In the final analysis, selection on a mix of phenotypic and
      molecular data is an essential step in evaluating its worth for improving a
      physiologically complex trait like egg production.

PMID- 9251141
TI  - Maximizing yield.
AB  - Genetic selection for edible meat yield will intensify as a result of market
      demands. Phenotypic selection in larger populations using nondestructive lean
      tissue estimation, more progeny and sibling carcass measurement, inclusion of
      female lines, and marker assisted selection will provide the means. Transgenics
      and genetic engineering will be used at the rate consumers accept them. As the
      kill age of birds decreases and edible meat yield increases, correlated concerns
      will include meat quality, bird immunocompetence, behavior, and reproduction.
      Higher yielding birds will be more difficult to manage.

PMID- 9251142
TI  - Effects on white Leghorn hens of constant exposure to ultraviolet light from
      insect traps.
AB  - Constant exposure of Hy-Line W-36 White Leghorn hens to ultraviolet light from
      insect traps resulted in no significant differences in egg production, fertility,
      hatchability of fertile eggs, or total hatchability. Also, there were no apparent
      effects on the eyes of the birds. Results were the same when either blacklight or
      blacklight blue tubes were used. The need for additional testing of light traps
      for nuisance fly control in commercial caged layer houses is discussed.

PMID- 9251143
TI  - Evaluation of leaves as a litter material.
AB  - The suitability of leaves for use as broiler litter was evaluated in four 49-d
      floor pen trials of 150 Avian x Avian female chickens each. In each trial, 25
      broiler chicks were weighed and randomly assigned to one of six pens at a density
      of 1.2 m2 per bird. There were two replicates of each of the following three
      treatments: 1) pine wood shaving (control), 2) a mix of 50% pine wood shaving and
      50% leaves, and 3) leaves. Litter materials had no significant (P > or = 0.05)
      influence on live weight, feed conversion, breast blisters, dressed carcass
      weight, carcass yield percentage, or mortality. Mortality of birds reared on
      leaves tended to be higher than the other treatments, but it was found to be
      nonsignificant at the P < 0.05 level. No significant differences were observed
      for percentage litter moisture among treatments. Body weight gain was
      significantly (P < or = 0.05) higher for the broilers reared on the leaf litter.
      Leaves alone or mixed with wood shavings have potential as an alternate litter
      material without compromising production or processing parameters at a low
      placement density.

PMID- 9251144
TI  - Effects of inorganic adsorbents and cyclopiazonic acid in broiler chickens.
AB  - Previous studies with cyclopiazonic acid (CPA) have indicated that this mycotoxin
      strongly adsorbs onto the surface of a naturally acidic phyllosilicate clay (AC).
      The objective of this study was to determine whether AC (and similar adsorbents)
      could protect against the toxicity of CPA in vivo. Acidic phyllosilicate clay,
      neutral phyllosilicate clay (NC, or hydrated sodium calcium aluminosilicate), and
      a common zeolite (CZ, or clinoptilolite) were evaluated. One-day-old broiler
      chicks consumed diets containing 0 or 45 mg/kg CPA alone or in combination with
      1% AC, NC, or CZ ad libitum from Day 1 to 21. Body weight, feed consumption,
      feed:gain, hematology, serum biochemical values, and enzyme activities were
      evaluated. Compared to controls, CPA alone reduced body weight at Day 21 by a
      total of 26% and resulted in a significantly higher feed:gain ratio. Toxicity of
      CPA was also expressed through increased relative weights of kidney,
      proventriculus, and gizzard. Also, there were some alterations in hematology,
      serum biochemical values, and enzyme activities. Treatment with inorganic
      adsorbents did not effectively diminish the growth-inhibitory effects of CPA or
      the increased weights of organs, although there was some protection from
      hematological, serum biochemical, and enzymatic changes produced by CPA. The
      results of this study suggest that in vitro binding of CPA to clay does not
      accurately forecast its efficacy in vivo; the reasons for this discrepancy are
      not clear, but they may be related to differences in clay binding capacity and
      ligand selectivity for CPA in vitro vs in vivo. Predictions about the ability of
      inorganic adsorbents to protect chickens from the adverse effects of mycotoxins
      should be approached with caution and should be confirmed in vivo, paying
      particular attention to the potential for nutrient interactions.

PMID- 9251145
TI  - Assessment of recombinant bovine somatotropin as an immunomodulator during avian
      coccidiosis: immunization with living oocysts.
AB  - Coccidiosis, a disease of great economic importance to the poultry industry, is
      generally controlled prophylactically by additions of anticoccidial drugs to the
      feed. However, increasing development of drug-resistant coccidia species has
      stimulated searches for alternative control methods, one of which is vaccination.
      As part of this effort, recombinant bovine growth hormone (rbST) was tested as a
      possible immune stimulator in combination with live oocyst vaccination. At a dose
      of 0.045 mg per chick, given by s.c. injection at 1 d of age, rbST did not
      improve immunity developed by immunization with 500 or 2,500 oocysts of Eimeria
      maxima as judged by weight gain and lesion scores. At a single dose of 0.09 mg
      per chick given at 1 d of age in combination with IMMUCOX, rbST provided some
      protection against challenge infection with Eimeria tenella but not Eimeria
      acervulina as judged by reduction in lesion scores. Treatment with 0.09 mg rbST
      per chick alone at 1 and 3 d of age was protective against challenge with E.
      tenella but not E. acervulina or E. maxima as judged by reduction in lesion
      scores. These results strongly indicate that rbST can act as an immune modulator
      in chickens infected with coccidia, and provide a basis for further
      investigations of its use as a vaccine adjuvant.

PMID- 9251146
TI  - Effects of components of Artemisia annua on coccidia infections in chickens.
AB  - Four experiments were run to test the anticoccidial activity of dried Artemisia
      annua leaves and several of their chemical constituents for possible use as
      prophylactic feed additives. When fed over a period of 3 wk at a level of 5%, a
      dried leaf supplement of A. annua provided significant protection against lesions
      due to Eimeria tenella but not Eimeria acervulina or Eimeria maxima. When fed
      over a period of 5 wk at a level of 1% to chicks undergoing immunization with a
      live vaccine, it provided significant protection in partially immunized chicks
      against E. acervulina and E. tenella lesions from a dual species challenge
      infection. It also afforded lower mean lesion scores in challenged chicks
      immunized over a period of 5 wk. Artemisinin, an antimalarial component of A.
      annua, was present at a level of 0.034% in the dried leaf preparation. A 5%
      supplement thus afforded about 17 ppm artemisin. When the pure compound was fed
      at that level for a period of 3 wk, it protected weight gains and significantly
      reduced lesion scores attributable to E. tenella but not E. acervulina. Other
      components of A. annua, camphor and 1,8-cineole, at 119 ppm also protected weight
      gains, and reduced E. tenella lesion scores. Camphor reduced E. acervulina
      lesions. Artemisinin fed for 4 wk at levels of 2, 8.5, and 17 ppm significantly
      reduced oocyst output from separate E. acervulina and E. tenella infections and a
      dual species infection. Pure artemisinin thus appears to be effective against at
      least two coccidia species when used as a feed additive, and its activity may
      depend, in part, on the length of time it is administered before a challenge
      infection.

PMID- 9251147
TI  - Dietary unsaturated fatty acids affect antibody responses and growth of chickens
      divergently selected for humoral responses to sheep red blood cells.
AB  - The effect of linoleic and linolenic acid on antibody (Ab) responses to SRBC and
      BSA and on growth performance were studied in pullets of three genetically
      different laying lines. Pullets were fed one of three diets: a control diet, a
      linoleic acid-enriched diet, or a linolenic acid enriched-diet. The linoleic and
      linolenic acid enriched-diets were the control diet enriched with either
      sunflower oil or linseed oil. Two chicken lines divergently selected for high (H)
      and low (L) Ab responses to SRBC, and a randombred control (C) line were used.
      Total Ab responses to SRBC were not affected by diet, but in the H line a
      tendency for higher IgG titers to SRBC after primary immunization were found when
      birds were fed the linoleic diet. The humoral response to BSA was significantly
      affected by a line by immunization by diet interaction. In the H line birds, the
      linoleic diet significantly enhanced Ab titers to BSA as compared to the normal
      diet and linolenic acid-enriched diet. The linolenic acid-enriched diet
      significantly decreased Ab titers to BSA in the C line birds. No dietary effects
      on the titer to BSA were found in the L line birds. During the first 3 wk of
      life, the linolenic acid-enriched diet resulted in reduced BW gain of H line
      birds. After that period, no effects of diet on BW gain was found. It is
      concluded that modulation of Ab responses of poultry to T cell-dependent antigens
      by essential fatty acids is affected by genotype. The relationship between
      magnitude of Ab responsiveness, BW, and essential fatty acids is discussed.

PMID- 9251148
TI  - Performance of commercial laying hens fed various phosphorus levels, with and
      without supplemental phytase.
AB  - A 17-wk study was conducted to evaluate the effects of supplementing laying hen
      diets with a commercially produced microbial phytase. Hy-Line W-36 pullets (21 wk
      of age) were randomly allocated to 1 of 10 diets in a factorial arrangement of
      five levels of nonphytate phosphorus (0.1 to 0.5% NPP) and two levels of phytase
      (0 and 300 U/kg feed). Dietary metabolizable energy, protein, and calcium were
      maintained at 2,816 kcal/kg, 16.6%, and 4%, respectively. Criteria evaluated
      included egg production, feed consumption, egg weight, egg specific gravity,
      mortality, and various bone quality parameters. Feeding 0.1% NPP without
      supplemental phytase decreased egg production (hen-housed) 8.1% over the entire
      study and 29.6% over the last 4 wk, relative to other diets without supplemental
      phytase. Similarly, feed consumption of hens fed 0.1% NPP without phytase
      decreased 5.8% over 17 wk and 13.0% over the last 4 wk. Egg production and feed
      consumption were maintained at the level of other treatments without phytase when
      the 0.1% NPP diet was supplemented with phytase (82.1% and 82.4 g per hen per d,
      respectively). Egg weights and egg specific gravity decreased and mortality
      increased when hens consumed 0.1% NPP without phytase. Supplementing the 0.1% NPP
      diet with phytase completely corrected these adverse effects. No deficiency
      symptoms were observed in hens fed diets containing 0.2 to 0.5% NPP. Phytase
      supplementation of these diets gave no further improvements in performance.

PMID- 9251149
TI  - A comparison of high current and low voltage electrical stunning systems on
      broiler breast rigor development and meat quality.
AB  - Experiments were conducted to compare the effects of a high current (HC) stunning
      system to a low voltage (LV) stunning system on broiler carcass and meat quality.
      A total of 360 broiler chickens were individually stunned using either 125 mA, 50
      Hz, constant AC for 5 s (HC) or using 10.5 V, 500 Hz pulsed DC for 10 s (LV).
      Birds were individually weighted, killed by conventional neck cut, bled for 150
      s, and reweighed to determine blood loss. Breast fillets (Pectoralis major) were
      removed from the carcass immediately after picking (0 h) or after aging for 24 h
      in a static ice-water slush. Breast muscle pH was determined at both 0 and 24 h.
      Raw breast meat color (CIELAB) and cooked breast meat Allo-Kramer shear values
      were determined on samples held at 2 C for 48 h. The LV stunning treatment
      significantly increased (P < 0.05) blood loss (4.0 vs 3.7%) and significantly
      reduced initial muscle pH (6.47 vs 6.67) when compared to the HC stunning
      treatment. There were no significant differences between the stunning systems for
      24 h pH, raw breast color, and Allo-Kramer shear. High current stunning reduced
      initial blood loss and delayed early rigor development compared to the LV
      treatment, but appeared to have little effect on final meat quality.

PMID- 9251150
TI  - A message from preventive medicine and your physician.

PMID- 9251151
TI  - Marital conflict in older adults: endocrinological and immunological correlates.
AB  - OBJECTIVE: To assess endocrinological and immunological correlates of marital
      conflict and marital satisfaction, 31 older couples (mean age 67 years) who had
      been married an average of 42 years were studied. METHOD: Couples were admitted
      to the Clinical Research Center and a catheter was placed in each subject's arm.
      Blood was drawn on entry for immunological assays; for hormone analyses, five
      blood samples were drawn during a 30-minute conflict discussion and a 15-minute
      recovery session. The conflict session was recorded on videotapes that were later
      coded for problem-solving behaviors using the Marital Interaction Coding System
      (MICS). RESULTS: Among wives, escalation of negative behavior during conflict and
      marital satisfaction showed strong relationships to endocrine changes, accounting
      for 16% to 21% of the variance in the rates of change of cortisol,
      adrenocorticotropic hormone (ACTH), and norepinephrine (but not epinephrine). In
      contrast, husbands' endocrine data did not show significant relationships with
      negative behavior or marital quality. Both men and women who showed relatively
      poorer immunological responses across three functional assays (the blastogenic
      response to two T-cell mitogens and antibody titers to latent Epstein-Barr virus)
      displayed more negative behavior during conflict; they also characterized their
      usual marital disagreements as more negative than individuals who showed better
      immune responses across assays. CONCLUSION: Abrasive marital interactions may
      have physiological consequences even among older adults in long-term marriages.

PMID- 9251152
TI  - Multilevel statistical models for psychosomatic research.

PMID- 9251153
TI  - Stress in employed women: impact of marital status and children at home on
      neurohormone output and home strain.
AB  - OBJECTIVE: To evaluate the biological and psychological effects of role overload,
      we examined the effects of marital (or partnership) status and parental status
      (defined as having children at home) on daily excretion of urinary catecholamines
      and cortisol in a sample of 109 employed women. Other measures included work and
      home strain, and social support. METHODS: Urine collection was conducted on two
      consecutive workdays in three separate aliquots, a) overnight, b) daytime, and c)
      evening. Repeated-measures analysis of covariance with age and caffeine
      consumption as covariates was conducted on levels of epinephrine, norepinephrine,
      and cortisol in the three aliquots averaged across the 2 days. RESULTS: We found
      a significant main effect of parental status on 24-hour cortisol excretion, (p <
      .01) such that women with at least one child living at home excreted
      significantly more cortisol, independent of marital status or social support.
      Women with children at home also reported higher home strain (p < .001) but not
      work strain. A significant period of day effect for catecholamine levels was
      found (norepinephrine, p < .001; epinephrine, p < .0001) with all subjects
      showing an increase during the workday and little or no decline in levels during
      the evening. Catecholamine levels were unrelated to marital status, parental
      status, or social support. CONCLUSIONS: These findings indicate that working
      women with children at home, independent of marital status or social support,
      excrete greater amounts of cortisol and experience higher levels of home strain
      than those without children at home.

PMID- 9251154
TI  - Stress in employed women: a woman's work is never done if she's a working mom.

PMID- 9251155
TI  - The control group dilemma in clinical research: applications for psychosocial and
      behavioral medicine trials.
AB  - OBJECTIVE: Clinical research on psychosocial and behavioral medicine
      interventions has burgeoned in the past two decades, so much so that sole
      reliance on standard no-treatment control conditions may no longer be appropriate
      or feasible. We discuss the ethical, theoretical, scientific, and statistical
      considerations that shape current clinical outcomes research for psychosocial and
      behavioral medicine interventions. METHOD AND RESULTS: Secondary analysis of a
      psychosocial randomized trial (N = 127) illustrates some of these points.
      CONCLUSIONS: A new design for randomized clinical trials is described that does
      not require a no-treatment control group, and that reveals dose-response
      relationships between interventions and treatment outcomes.

PMID- 9251156
TI  - Short stature, growth hormone deficiency, and social anxiety.
AB  - OBJECTIVE: We have reported high rates of social phobia in growth hormone
      deficient (GHD) adults who had been treated with growth hormone during childhood.
      This follow-up study was conducted to determine whether the increased social
      phobia observed in GHD subjects was secondary to the effects of short stature.
      METHODS: Twenty-one age- and sex-matched non-GHD short adults were evaluated for
      social anxiety and compared with the previously studied 21 GHD subjects. RESULTS:
      Thirty-eight percent (8 of 21) of GHD and 10% (2 of 21) of short subjects met DSM
      III-R criteria for social phobia. GHD subjected scored significantly higher than
      short subjects on the following self-report questionnaires: Fear of Negative
      Evaluation (p = .03), Fear Questionnaire (p = .01), Social Avoidance and Distress
      Scale (p = .01), Beck Depression Inventory (p = .007), and the Tridimensional
      Personality Questionnaire-harm avoidance subscale (p = .0004). CONCLUSIONS: These
      data suggest that the high prevalence of social phobia in GHD adults is not
      explained by short stature alone.

PMID- 9251158
TI  - Serum cholesterol and intellectual performance.
AB  - OBJECTIVE: The current investigation sought to determine whether intellectual
      performance is related to serum lipid concentrations. METHODS: Subjects were 177
      healthy, Caucasian adult males and females, aged 25 to 60 years, with widely
      varying total cholesterol concentrations. Crystallized intelligence was estimated
      from the Information and Vocabulary subtests of the Wechsler Adult Intelligence
      Scale, Revised (WAIS-R). Fluid intelligence was estimated from the WAIS-R Block
      Design subtest, and from a computerized version of the Letter Rotation test.
      RESULTS: Controlling for age, better performance on both Information and
      Vocabulary subtests was associated with lower total and low-density lipoprotein
      (LDL) cholesterol and triglyceride concentrations (r's = -.24 to -.35, p's <
      .005). In contrast, better performance on Block Design was correlated with higher
      total and LDL cholesterol (r's = .22 to .23, p's < .005). Letter rotation
      response latency was unrelated to serum lipids. CONCLUSION: These opposing
      relationships between serum cholesterol and different dimensions of intellectual
      performance, on the one hand, may reflect the propensity of knowledgeable
      individuals to consume low fat diets, and on the other hand, suggest that serum
      cholesterol concentration may be a correlate of brain nutrients important to
      mental efficiency.

PMID- 9251157
TI  - Determinants of endothelium-dependent femoral artery vasodilation in youth.
AB  - OBJECTIVE: Decreased endothelium-dependent arterial dilation to reactive
      hyperemia has been shown in adults to be associated with various manifestations
      of cardiovascular diseases and cardiovascular risk factors. In a sample of
      children, we examined the relationships between flow-mediated femoral artery
      dilation and anthropometric, demographic, cardiovascular, and serum lipid
      variables that have been associated with cardiovascular diseases. METHOD: Thirty
      three asymptomatic, healthy 11 to 14 years olds were randomly selected from
      participants in a longitudinal cardiovascular health study. There were 17 boys
      and 16 girls; 21 whites and 12 blacks. Sixteen had documented family history of
      premature myocardial infarction (ie, < or = 55 years of age) in first-degree
      relatives and 17 did not. Measurements included fasting lipids, anthropometrics,
      blood pressure and heart rate at rest and during supine exercise, postural
      change, and forehead cold stimulation. Femoral artery dilation to reactive
      hyperemia was measured via high resolution ultrasound. RESULTS: Bivariate
      analyses indicated flow-mediated dilation was negatively correlated with systolic
      pressure increases to postural change, forehead cold stimulation and dynamic
      exercise, greater average skinfold thickness, and body fat via dual x-ray
      absorptiometry and positively correlated with cardiovascular fitness (all ps <
      .05). Stepwise multiple regression revealed that cardiovascular fitness and
      systolic pressure reactivity to exercise significantly predicted flow-mediated
      dilation accounting for 31% of the variance (p < .01). CONCLUSIONS: Decreased
      flow-mediated dilation is associated with decreased cardiovascular fitness,
      increased systolic pressure reactivity to various stressors, and increased
      indices of body fatness in asymptomatic youth. Further research is warranted to
      better understand early relationships between this noninvasive measure of
      endothelial function and cardiovascular risk factors in youth.

PMID- 9251159
TI  - Social support effects on cardiovascular reactivity: is a stranger as effective
      as a friend?
AB  - OBJECTIVE: We investigated whether the effects on cardiovascular reactivity of
      social support from an audience member depend only on the behavior of that person
      or also depend on the relationship between the audience and the actor. That is,
      is there any added reduction in physiological response if the person who is
      nodding and smiling supportively is also a friend? METHOD: Ninety subjects gave a
      speech to an observer. In two of the conditions, this observer was a confederate
      of the experimenter and a stranger to the subject. This confederate acted in
      either a supportive or neutral manner during the speech. In the final condition,
      this observer was a friend, brought by the subject, who was then trained to show
      support in the same manner as the supportive confederate. The comparison of the
      two confederate conditions tested the effect of support, holding the relationship
      constant. The comparison of friend and confederate supportive conditions tested
      the effect of the relationship, holding the supportive behaviors constant. All
      participants were female. RESULTS: Both supportive conditions produced
      significantly smaller cardiovascular increases than the confederate-neutral
      condition, and the friend-supportive condition produced significantly smaller
      systolic blood pressure increases than the confederate-supportive (friend
      supportive: 7.9 mm Hg: confederate-supportive: 14.9 mm Hg; confederate-neutral:
      22.9 mm Hg). Differences for diastolic pressure and heart rate were not
      significant, although the data followed the same pattern. CONCLUSIONS: Social
      support from a friend attenuated cardiovascular reactivity in a laboratory
      setting to a greater degree than support from a stranger. The subjects' construal
      of the supportive behaviors can have an effect on reactivity, over and above the
      effects of the actual behaviors themselves.

PMID- 9251160
TI  - Inhibition of subjective and physiological sexual arousal in women by clonidine.
AB  - OBJECTIVE: The present investigation was designed to provide the first empirical
      examination of the effects of clonidine, a selective alpha 2-adrenergic agonist,
      on sexual arousal in women with and without prior sympathetic nervous system
      [SNS] stimulation by exercise. The purpose was to help elucidate the influence of
      adrenergic mechanisms on sexual function in women. METHODS: Thirty sexually
      functional women participated in two experimental sessions in which subjective
      (self-report) and physiological (vaginal photoplethysmograph) sexual responses to
      erotic stimuli were measured after either clonidine (0.2 mg) or placebo
      administration in a randomized, double-blind, crossover protocol. Before viewing
      the experimental films, 15 subjects engaged in 20 minutes of intense exercise
      designed to elicit significant SNS activation. RESULTS: Clonidine significantly
      decreased vaginal pulse amplitude, vaginal blood volume, and subjective sexual
      responses to the erotic films in subjects who were in a state of heightened (via
      exercise), but not baseline (no exercise) SNS arousal. CONCLUSIONS: Clonidine can
      significantly inhibit subjective and physiological sexual arousal in women. These
      findings have implications for deriving an etiological theory of sexual function
      in women and for understanding the effects of psychotherapeutic drugs on female
      sexual function.

PMID- 9251161
TI  - Coping and psychosocial adaptation: longitudinal effects over time and stages in
      breast cancer.
AB  - OBJECTIVES: This study examined the relationship between coping and psychosocial
      adaptation in cancer patients over time and across distinct clinical events.
      METHODS: In a prospective longitudinal study 74 patients with breast cancer were
      observed for 3 to 5 years at 3- to 6-month intervals. A total of 684 interviews
      were conducted at different observation points. Three rating scales were used to
      assess coping and adjustment: first, the Bernese Coping Modes, an observer rating
      scale devised to elicit 26 coping modes aggregated in this paper as the five
      Basic Coping Strategies of support, self-control, denial, diverting, and negative
      emotional; second, an observer rating scale to ascertain psychosocial adaptation;
      and third, a self-rating scale as a measure of either emotional distress or well
      being. RESULTS: a) When aggregated in illness stages, coping and distress data on
      the observed clinical time points showed greater variability than time measures
      alone (analysis of variance (ANOVA) for repeated measures p < .001). b) A
      significant relationship between the Basic Coping Strategies and psychosocial
      adaptation was demonstrated using discriminant and correlational analysis.
      Furthermore, in stage-dependent Pearson r correlations (p < .05 to .001), a clear
      cut relationship was found for hospitalization, chemotherapy, and rehabilitation,
      but not for convalescence and metastasis. c) A positive relationship was
      demonstrated between psychosocial adaptation and strategies that can be generally
      categorized as good forms of coping such as support and self-control, and, to a
      lesser degree, diverting and denial. Conversely, poor coping exerted a negative
      effect on almost all illness stages and on most criteria of adjustment.
      CONCLUSIONS: In long-term studies on psychosocial adaptation and coping, stage
      related measures should be preferred to time measures alone. The implications of
      different strategies for the psychological treatment of cancer patients are
      discussed.

PMID- 9251162
TI  - Attenuated free cortisol response to psychosocial stress in children with atopic
      dermatitis.
AB  - OBJECTIVE: Atopic dermatitis (AD) is an inflammatory skin disease characterized
      by a hyperactivity of the humoral immune system with an onset in infancy or early
      childhood. Although most of the research has focused on the pathophysiological
      role of the immune system in AD, the impact of endocrine signals in the pathology
      of AD has received only little attention. However, because the endocrine system
      may play a regulatory role in immune functioning, it might be of major interest
      to study endocrine reactivity in AD patients. The present two-part study
      investigated the relationship between adrenocortical stress response, heart rate
      response, and psychological parameters in children with AD. METHOD AND RESULTS:
      In Study 1, a protocol for induction of psychosocial stress in children aged 8 to
      14 years was evaluated. Healthy children (N = 16) were exposed to the Trier
      Social Stress Test for Children (TSST-C) that mainly consists of public speaking
      and mental arithmetic tasks in front of an audience. Salivary cortisol was
      measured 35, 15, and 1 minute before as well as 1, 10, 20, and 30 minutes after
      the stress; heart rate was monitored continuously. Results showed that the
      protocol induced a highly significant increase in free cortisol response (p <
      .001) and heart rate (p < .001). In Study 2, the TSST-C was applied to AD
      children (N = 15) and age- and sex-matched healthy controls (N = 15). All
      patients were in remission and medication-free for at least 3 weeks. Again, the
      stress test induced significant increases in cortisol and heart rate. However,
      the AD children showed a significantly blunted cortisol response to the stressor
      compared with the control group (p < .05). Heart rate responses were similar in
      both experimental groups. Neither subjective stress ratings nor personality
      traits were related to the blunted cortisol response. CONCLUSIONS: These findings
      suggest that the adrenocortical response to stress is attenuated in atopic
      children. A hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis might
      explain in part the stress-induced eruptions of AD symptoms.

PMID- 9251163
TI  - Differences in salivary habituation to palatable foods in bulimia nervosa
      patients and controls.
AB  - OBJECTIVE: Bulimia nervosa (BN) patients have been shown to experience anomalous
      responses to food and food cues. We investigated the response to food over time
      by presenting repeated food cues and measuring changes in physiological (ie,
      salivation) and subjective responses. METHOD: Subjects were 18 BN women and 18
      matched control women. Two palatable food stimuli, regular or frozen yogurt, that
      varied in macronutrient composition but had similar sensory characteristics, were
      presented to subjects repeatedly during a laboratory session. After two baseline
      salivation measures, subjects were presented with eight trials of one of the two
      yogurts. On Trial 9 a lemon juice dishabituator was presented, with the yogurt
      stimulus presented again at Trial 10. RESULTS: We found that control subjects had
      decreased salivation after repeated food presentations. In comparison, BN
      subjects failed to show a decrease in salivation. The desire to binge increased
      over trials for the BN subjects, but remained stable for normals. CONCLUSIONS:
      These data suggest that salivary habituation may be abnormal in BN patients.

PMID- 9251164
TI  - Influence of ethnicity and gender on cardiovascular responses to active coping
      and inhibitory-passive coping challenges.
AB  - OBJECTIVE: The goal of this study was to evaluate how black and white men and
      women responded physiologically to specific laboratory challenges. METHODS:
      Hemodynamic responses to an active coping (evaluated speaking) and two inhibitory
      passive coping (mirror tracing, cold pressor) tasks were examined in 138 black
      and white men and women. RESULTS: Significant ethnicity by gender interactions
      occurred for the evaluated speaking task. Black men responded with lower blood
      pressure, cardiac output or heart rate, or both, than black women, white men, and
      white women, who did not differ from each other. Black men, relative to the other
      subgroups, also reported more inhibitory-passive coping, hostility, and
      pessimism, and less social support. Whites also responded with greater increases
      in systolic blood pressure during mirror tracing than blacks. CONCLUSIONS: These
      findings indicate that black-white differences in physiological responsivity
      obtained for men may have limited generalizability for women. The results also
      suggest that environmental and social factors rather than genetic or
      constitutional factors may play a role in black-white reactivity differences.

PMID- 9251165
TI  - Chronic life stress alters sympathetic, neuroendocrine, and immune responsivity
      to an acute psychological stressor in humans.
AB  - OBJECTIVE: Life stress is hypothesized to alter the dynamic regulation of the
      autonomic, neuroendocrine, and immune systems. This study examined the effects of
      antecedent chronic life stress on psychological and physiological responsivity
      after acute challenge with a psychological stressor. METHOD: Using a within
      subject mixed design, male volunteers with (N = 12) and without chronic life
      stress (N = 11) were administered a 12-minute laboratory stressor (mental
      arithmetic) vs a video control. RESULTS: Acute psychological stress induced
      subjective distress, increases of circulating concentrations of epinephrine,
      norepinephrine, beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol,
      and a selective redistribution of natural killer (NK) cells into the peripheral
      blood as compared with the video control condition. Although the two groups were
      almost identical at baseline in psychological, sympathetic, neuroendocrine, and
      immune domains, the chronic stress group showed greater subjective distress,
      higher peak levels of epinephrine, lower peak levels of beta-endorphin and of NK
      cell lysis, and a more pronounced redistribution of NK cells in response to the
      acute psychological challenge than the controls. Furthermore, the acute stressor
      induced a protracted decline in NK lysis per NK cell in the chronic stress group
      but had no effect in the controls. CONCLUSIONS: In summary, when persons who are
      undergoing chronic life stress are confronted with an acute psychological
      challenge, an exaggerated psychologic and peak sympathomedullary reactivity
      occurs that is associated with decrements in individual NK cell function and is
      protracted beyond termination of the stressor and sympathomedullary recovery.

PMID- 9251166
TI  - Tricompartmental kinetics of the organophosphorous pesticide dimethoate.
AB  - We present a study on the distribution and persistence of the organophosphorous
      pesticide, dimethoate, in the Wistar rat. Dimethoate's levels in blood and
      tissues were determined using gas chromatography with a NPD detector. The
      toxicokinetic profile was estimated by non-linear regression using the software
      program PCNONLIN, which concluded that a tricompartmental model best described
      dimethoate's behavior in the rat body.

PMID- 9251167
TI  - Effect of roundup and tordon 202C herbicides on antibody production in mice.
AB  - Female CD-1 mice were exposed to Tordon 202C (2,4-dichlorophenoxyacetic acid [2,4
      D] and picloram) or Roundup (glyphosate) in drinking water for 26 d at
      concentrations ranging from 0 to 0.42% or from 0 to 1.05%, respectively. The mice
      were inoculated with sheep red blood cells to produce a T-lymphocyte, macrophage
      dependent antibody response on day 21 of the herbicide exposure period. Tordon
      202C dosing reduced weight gain and water consumption at the 0.42% level of
      exposure. Roundup exposure did not alter weight gain or water consumption.
      Antibody production was unaffected by Roundup dosing, suggesting that Roundup is
      unlikely to cause immune dysfunction under normal application conditions. In
      contrast, all levels of Tordon 202C exposure reduced antibody production by as
      much as 45%. The immunosuppressive activity of Tordon 202C was associated with
      levels more than 12 x the normal application level, although it was not
      determined which component of the formulation was responsible for the
      immunosuppression effect. The presence of immune alteration subsequent to
      exposure to Tordon 202C at levels marginally above the normal application levels
      suggests that chronic exposure to Tordon 202C in the environment has the
      potential to alter immune function.

PMID- 9251168
TI  - Antidotal efficacy of glutamate and aspartate for colchicine toxicity.
AB  - Glutamic and aspartic acids were evaluated for their antidotal efficacy in
      colchicine toxicity. Female adult inbred mice were treated with ip doses of
      either 1000 mg glutamic acid (GA) or aspartic acid (AA)/kg bw by various
      treatment schedules relative to the administration of an ip LD5n of 7.8 mg
      colchicine/kg bw. Mice were observed for survival and changes in body weight.
      Pretreatment with AA increased survival by 42% (p = 0.01). Concurrent AA
      treatment improved survival non-significantly (p = 0.07). With post-exposure AA
      therapy, however, mortality was increased (p = 0.005). No significant beneficial
      effects of GA occurred. Early AA therapy improves survival in colchicine poisoned
      mice, but as delay in treatment is increased, AA efficacy is lost.

PMID- 9251169
TI  - Influence of 3,4-dihydroxybenzoic acid on metal ion concentrations in guinea pig
      tissues after copper intoxication.
AB  - 3,4-Dihydroxybenzoic acid (3,4-dhbH3 or protocatechuic acid) is a copper chelator
      which has potential as an agent for the treatment of copper-overload disease
      (Wilson's disease). The present investigation describes the fluctuation in
      copper, magnesium, zinc and calcium (Cu, Mg, Zn, Ca) concentrations in tissues of
      guinea pigs intoxicated with Cu after the administration of 3,4-dhbH3. We
      investigated the efficacy of 3,4-dhbH3 to eliminate Cu from poisoned guinea pigs,
      as well as to assess the changes in concentrations of Zn, Ca and Mg which
      normally occur in the tissues of experimental animals. The results are in
      agreement with other experimental data when we administered drugs capable of
      forming complexes with metal ions. Although 3,4-dhbH3 is capable of forming in
      vitro complexes with Cu, it can not be used successfully for chelation therapy of
      Cu intoxication, but its effectiveness as a ligand for Ca, Zn and Mg mobilization
      is discussed.

PMID- 9251170
TI  - Potentiation of pyridostigmine bromide toxicity in mice by selected adrenergic
      agents and caffeine.
AB  - Pyridostigmine bromide (PB) is a reversible cholinesterase inhibitor used
      routinely in the treatment of myasthenia gravis and recently by the US Army as a
      prophylactic agent against potential nerve gas attack in the Persian Gulf War.
      Pyridostigmine has been implicated as one of several possible causative factors
      associated with Persian Gulf illnesses. To investigate toxic interactions between
      PB and other drugs, male ICR mice received contralateral ip injections of either
      a selected adrenergic drug or caffeine, followed 15 min later by PB.
      Representative isobolograms plotted for each drug interaction illustrate that a
      beta-adrenoceptor agonist (isoproterenol), selective beta 2-adrenoceptor agonists
      (salbutamol, terbutaline), alpha 1- and alpha 2-adrenoceptor antagonists
      (yohimbine, phentolamine, prazosin), as well as the stimulant caffeine, strongly
      potentiate the lethal effect of PB. Agents with agonist activity at both alpha-
      and beta-adrenoceptors (epinephrine, norepinephrine) additively increase PB
      induced lethality. The potentiation of toxicity between PB and these agents was
      counteracted by pretreatment with atropine and atropine methyl nitrate. An alpha
      2-adrenoceptor agonist (clonidine) and beta-adrenoceptor antagonists
      (propranolol, nadolol, acebutolol) did not increase PB-induced lethalities. These
      data demonstrate a toxic synergism between PB, several commonly used classes of
      adrenergic agents and caffeine when exposure occurs in different combinations.
      Future studies into the mechanism(s) of these interactions may bring into
      question the usage of PB as a protective agent in combat conditions as well as
      delineate any possible contributions of the drug to Persian Gulf illnesses.

PMID- 9251171
TI  - Fumonisin exposure to Kansans through consumption of corn-based market foods.
AB  - Fumonisins are secondary metabolites of the fungus Fusarium moniliforme Sheldon,
      a common corn contaminant world wide. Presently 6 different fumonisins (FB1, FB2,
      FB3, FB4, FA1 and FA2) have been identified and characterized. In veterinary
      medicine fumonisins cause equine leucoencephalomalacia and swine pulmonary edema.
      In addition, fumonisins have been shown to be carcinogenic in laboratory animals
      and have been linked to human esophageal cancer in South Africa and China. In
      this study we examined the prevalence of FB1, FB2 and FB3 in corn-based human
      foods in Kansas using HPLC equipped with a fluorescent detector. All 3 fumonisins
      were detected in at least 1 food item. However, only 24/121 samples analyzed
      (20%), contained detectable (> 40 ppb) fumonisins. Corn flour was the most
      frequently contaminated as 13/25 items (52%) were positive for fumonisins. For
      all analyzed human foods, the range of fumonisins was 42-350 ppb in comparison to
      765-9953 ppb found in corn meant for animal consumption. This data shows that
      corn flour is the item most likely to be contaminated with low concentrations of
      fumonisins. Corn-based foods do not appear a significant source of fumonisins for
      Kansans although the implications to human health of these low levels are
      unknown.

PMID- 9251172
TI  - Determination of nicotine content of popular cigarettes.
AB  - Accidental cigarette ingestion by children is a frequent occurrence in Japan
      where hundreds of cigarette brands (domestic and imported) are purchased. To
      evaluate the predictive value of the nicotine yield given on the label and
      determined by a smoking machine, we measured the actual nicotine content of
      tobacco in 33 popular cigarette brands. Average amounts of nicotine and
      tobacco/whole cigarette of 32 filter and 1 non-filter brands were as follows:
      11.72 +/- 2.27 (SD) mg nicotine (range 6.94-18.33 mg) and 23.97 mg tobacco, and
      0.67 +/- 0.07 g nicotine (range 0.49-0.79 g) and 1.02 g tobacco, respectively.
      Amounts of nicotine and tobacco in filter brands varied widely and were less than
      the data reported in the toxicological literature. Measured lengths of the part
      of cigarettes packed with tobacco ranged from 5.0 to 6.9 cm. The tobacco in low
      yield cigarettes did not contain less nicotine than high-yield cigarettes, and
      the nicotine yield did not highly correlate with the nicotine content in the low
      yield cigarette group (r = 0.243). We conclude that the nicotine yields on labels
      are not useful in estimating likely nicotine intake in cigarette-ingestion cases.
      The actual nicotine content of cigarettes should be included on the product
      label.

PMID- 9251173
TI  - Acute caffeine ingestion fatalities: management issues.
AB  - Caffeine is used and abused on a daily basis in different beverages, OTC
      products, and as a prescribed medication. The strength varies widely from
      negligible in decaffeinated drinks to medicinal grade of 200 mg/tablet. A total
      of 7,655 exposures were recorded in 1995 by the AAPCC Toxic Exposure Surveillance
      System with no fatality. However, within a 4-mo period, the Panhandle Poison
      Center recorded 2 deaths due to caffeine overdose. The abrupt onset of
      intractable seizures needs to be anticipated in order to appropriately manage the
      victims and to prevent the adverse outcome.

PMID- 9251174
TI  - Cisapride poisoning.
AB  - A MEDLINE search from 1966-1996 revealed no reports of cisapride poisoning. An 8
      mo-old, 8.9 kg girl received 8 mL of cisapride (Propulsid Suspension, 1 mg/mL,
      Janssen Pharmaceutica, Titusville, NJ) rather than the usual dose of 0.8 mL,
      resulting in an inadvertent, 10-fold, iatrogenic, dosing error. She developed
      emesis, hyperactive bowel sounds, abnormal behavior, mild hyperthermia,
      tachycardia, hypertension, and thrombocytosis. This is the first published report
      of poisoning with cisapride.

PMID- 9251176
TI  - Scombroid fish poisoning: an overlooked marine food poisoning.
AB  - Scombroid fish poisoning is a food-borne chemical intoxication caused by certain
      spoiled fish that contain a large amount of histamine and some biogenic diamines.
      It has gradually become a world-wide medical problem and probably is the most
      common cause of fish poisoning. As the data on the incidents of scombroid fish
      poisoning in Taiwan remains scarce, we report 2 incidents of scombroid fish
      poisoning in Northern Taiwan. We collected data of the 2 outbreaks of suspected
      fish poisoning which were reported to us in 1996. An epidemiological
      investigation was undertaken. Questionnaire interviews were given to persons who
      ate lunch in the same cafeteria in outbreak 2. The leftover fish were sent for
      species identification and toxin analysis. The first incident involving 4 women
      occurred in March 1996. All cases experienced flush, dizziness, blurred vision
      and skin rashes after eating lunch. A non-scombroid fish of Makaira with
      histamine levels as high as 84.13 mg/100 g flesh was implicated in this incident.
      In August 1996, another incident involving some cases who ate lunch at the same
      cafeteria were investigated. A total of 146 questionnaires were distributed with
      a return of 132 questionnaires (90.4%). Fifty-five employees reported positive
      signs or symptoms; 48 persons who ate fish and 7 women who did not eat fish were
      ill. Fish was the only food associated with the illness with an attack rate of
      73.8% (p < 0.001). The incriminated fish was later identified as a scombroid fish
      of Euthynnus with a histamine content of 271.9 mg/100 g flesh in 1 leftover piece
      and 118.5 mg/100 g flesh in another piece. Most cases in these 2 outbreaks
      received treatment with antihistamines and had rapid and complete recovery. The
      diagnosis of scombroid fish poisoning could be misdiagnosed as food allergy or
      bacterial food poisoning if physicians are not aware of such poisoning. The
      nonspecific but characteristic symptomatology of histamine food poisoning and
      previous consumption of fish should alert physicians to the possibility of
      scombroid fish poisoning. Unless complicated with shock or respiratory distress,
      supportive treatment with antihistamines usually concludes with a good prognosis.
      Toxin analysis of the fish flesh remains the most important step in approaching a
      confirmed diagnosis.

PMID- 9251175
TI  - Gamma butyrolactone poisoning and its similarities to gamma hydroxybutyric acid:
      two case reports.
AB  - Clinical experience with toxicity induced by products containing gamma
      butyrolactone is limited. We report here 2 cases of gamma butyrolactone poisoning
      with a nail polish remover labelled "acetone-free". Rapid onset of coma,
      respiratory depression and bradycardia occurred in both patients. After
      supportive care, they fully recovered within a few hours.

PMID- 9251177
TI  - MDEA related death in Crete: a case report and literature review.
AB  - "Designer drugs" are derivatives of approved drugs abused for recreational effect
      and created by underground laboratories to circumvent legal restriction. By far
      the most controversial drug has been MDMA (3,4-methylenedioxymethamphetamine) and
      the newer derivative MDEA (3,4-methylenedioxymethamphetamine) often called "Eve".
      MDEA-related deaths have not been reported in the US, but there have been a death
      of MDMA and MDEA severe poisonings. Convulsions, collapse, hyperpyrexia,
      disseminated intravascular coagulation rhabdomyolysis, and acute liver and renal
      damage result from the ingestion of the drug. Complications may occur and
      severity and death possibly result. The case of a 31-y-old male, the first victim
      of MDEA in Greece, is reported. Blood MDEA was 3.1 micrograms/mL; MDEA
      concentrations in liver, lung and kidney were 4.8, 5.2, and 4.8 micrograms/g
      respectively.

PMID- 9251179
TI  - A position on reduced diet and longevity.

PMID- 9251178
TI  - Emergency department use of flumazenil prior to poison center consultation.
AB  - We studied the frequency of use of flumazenil by emergency departments in our
      region and compared it to recommendations made by specialists in poison
      information at our poison control center. For a 5-mo period, we prospectively
      collected cases involving benzodiazepines or zolpidem. Data was documented only
      from calls from emergency departments. Emergency department personnel were asked
      the following: If given, the dose and frequency, contraindications, and adverse
      reactions. Each case was followed to completion. Flumazenil was not given in 55
      cases. Of the remaining 14 cases in which it was given, 10 of the cases received
      flumazenil prior to poison control center consultation. We noted 1 case of
      dizziness. Ten cases given flumazenil had contraindications (eg ethanol abuse or
      possible seizurogenic coingestants). Despite possible contraindications,
      flumazenil was given 10/14 times (71%) prior to calling the poison control
      center. These results point to potential overuse of this antidote where
      contraindications or cautions are suspected in the overdosed patients. Our study
      suggests that when flumazenil use is contemplated by an emergency department
      physician, a poison control center consult may have a contrary recommendation.

PMID- 9251180
TI  - Plant exposures ... a national profile of the most common plant genera.
AB  - Plant exposures are the 4th most common cause of poisoning and 85% of those
      exposures involve the pediatric population. The large number of plant-related
      exposures and the lack of knowledge about plant toxicity has led to plant
      paranoia and considerable educational efforts to reduce the number of exposures.
      These efforts are often dictated by misconceptions and folklore. American
      Association of Poison Control Centers (AAPCC) data on all plant exposures for the
      years 1985-1994 were electronically analyzed by plant genus to establish a
      frequency distribution of all plant exposures in the United States. A total of
      912,534 plant exposure cases were analyzed to tabulate the top 100 plant
      exposures. Philodendron spp were the most common exposures, followed by
      Dieffenbachia spp, Euphorbia spp, Capsicum spp and Ilex spp. Plant exposures are
      very common and poison information centers devote significant clinical service
      and educational effort to manage these exposures and enhance the public's
      awareness. Awareness of specific plant species and exposure frequency in a poison
      center region can serve as a basis for staff education and as the cornerstone for
      the development of appropriate information in poison prevention and education
      brochures. This can direct better utilization of poison center financial
      resources.

PMID- 9251181
TI  - Presumptive intoxication of cattle by corn cockle, Agrostemma githago (L) Scop.

PMID- 9251182
TI  - Evaluation of luciferase reporter bacteriophage A511::luxAB for detection of
      Listeria monocytogenes in contaminated foods.
AB  - A511::luxAB is a recombinant derivative of a broad-host-range bacteriophage
      specific for the genus Listeria, transducing bacterial bioluminescence into
      infected cells. In this study, we have evaluated its use for rapid and easy
      testing of contaminated foods and environmental samples for the presence of
      viable Listeria cells, in comparison to the standard plating procedure. With a
      short preenrichment step of 20 h, the system was capable of detecting very low
      initial contamination rates in several foods artificially contaminated with
      Listeria monocytogenes Scott A cells. In ricotta cheese, chocolate pudding, and
      cabbage, less than one cell per g of food could be clearly identified by
      comparing the light emission of phage-infected samples to that of controls
      without lux phage. In foods having a large and complex microbial background
      flora, such as minced meat and soft cheese, at least 10 cells per g were
      necessary to produce a positive bioluminescence signal. Of 348 potentially
      contaminated natural food and environmental samples, 55 were found to be Listeria
      positive by the lux phage method. The standard plating procedure detected 57
      positive samples. Some differences were observed with respect to the individual
      samples, i.e., the lux phage procedure detected more positive samples among the
      dairy products and environmental samples, whereas the plating procedure revealed
      more contaminated meat and poultry samples. Overall, both methods performed
      similarly, i.e., were equally sensitive. However, the minimum time required for
      detection of Listeria with the luciferase phage assay was 24 h, which is much
      shorter than the 4 days needed by the standard plating method. Furthermore, a
      most probable number technique with three parallels, based on the use of
      A511::luxAB for differentiation of positive and negative tubes, is described. The
      method enables rapid enumeration of low levels of Listeria cells in several foods
      tested, against the background of a competing microflora.

PMID- 9251183
TI  - A mutation in the 14 alpha-demethylase gene of Uncinula necator that correlates
      with resistance to a sterol biosynthesis inhibitor.
AB  - We investigated the molecular basis of resistance of the obligate biotrophic
      grape powdery mildew fungus Uncinula necator to sterol demethylation-inhibiting
      fungicides (DMIs). The sensitivity of 91 single-spore field isolates of U.
      necator to triadimenol was assessed by using a leaf disc assay. Resistance
      factors (RF) ranged from 1.8 to 26.0. The gene encoding the target of DMIs
      (eburicol 14 alpha-demethylase) from five sensitive and seven resistant isolates
      was cloned and sequenced. A single mutation, leading to the substitution of a
      phenylalanine residue for a tyrosine residue at position 136, was found in all
      isolates exhibiting an RF higher than 5. No mutation was found in sensitive or
      weakly resistant (RF, < 5) isolates. An allele-specific PCR assay was developed
      to detect the mutation. Among the 91 isolates tested, only isolates with RF
      higher than 5 carried the mutation. Three of the 19 resistant isolates and all
      sensitive and weakly resistant isolates did not possess the mutation. The
      mutation at codon 136 is thus clearly associated with high levels of resistance
      to triadimenol.

PMID- 9251184
TI  - Induction of lipid peroxidation during heavy metal stress in Saccharomyces
      cerevisiae and influence of plasma membrane fatty acid unsaturation.
AB  - The degree of plasma membrane fatty acid unsaturation and the copper sensitivity
      of Saccharomyces cerevisiae are closely correlated. Our objective was to
      determine whether these effects could be accounted for by differential metal
      induction of lipid peroxidation. S. cerevisiae S150-2B was enriched with the
      polyunsaturated fatty acids (PUFAs) linoleate (18:2) and linolenate (18:3) by
      growth in 18:2- or 18:3-supplemented medium. Potassium efflux and colony count
      data indicated that sensitivity to both copper (redox active) and cadmium (redox
      inactive) was increased in 18:2-supplemented cells and particularly in 18:3
      supplemented cells. Copper- and cadmium-induced lipid peroxidation was rapid and
      associated with a decline in plasma membrane lipid order, detected by
      fluorescence depolarization measurements with the membrane probe
      trimethylammonium diphenylhexatriene. Levels of thiobarbituric acid-reactive
      substances (lipid peroxidation products) were up to twofold higher in 18:2
      supplemented cells than in unsupplemented cells following metal addition,
      although this difference was reduced with prolonged incubation up to 3 h.
      Conjugated-diene levels in metal-exposed cells also increased with both the
      concentration of copper or cadmium and the degree of cellular fatty acid
      unsaturation; maximal levels were evident in 18:3-supplemented cells. The results
      demonstrate heavy metal-induced lipid peroxidation in a microorganism for the
      first time and indicate that the metal sensitivity of PUFA-enriched S. cerevisiae
      may be attributable to elevated levels of lipid peroxidation in these cells.

PMID- 9251185
TI  - Amy as a reporter gene for promoter activity in Nocardia lactamdurans: comparison
      of promoters of the cephamycin cluster.
AB  - Promoter probe vectors containing the pA origin of replication and the
      Streptomyces griseus promoterless amy gene (encoding alpha-amylase) as reporter
      have been constructed to study transcription initiation regions in Nocardia
      lactamdurans. In some of the promoter probe vectors the phage fd terminator has
      been introduced to avoid readthrough expression from upstream sequences. By using
      these vectors, four different transcription initiation regions of the cephamycin
      gene cluster have been studied in N. lactamdurans. The bla gene encoding a beta
      lactamase has a relatively strong promoter. Two other separate promoters
      corresponding to the lat and cefD genes (encoding, respectively, lysine-6
      aminotransferase and isopenicillin N-epimerase) showed weak transcription
      initiation ability. These two promoters are arranged in a bidirectional
      transcription initiation region located in the center of the cephamycin gene
      cluster. The cmcH gene (encoding 3-hydroxymethylcephem carbamoyltransferase)
      upstream region did not contain a functional promoter, suggesting that cmcH is
      transcribed as a part of a polycistronic mRNA. The native amy promoter is used
      very efficiently in N. lactamdurans, resulting in secretion of high levels of
      extracellular alpha-amylase.

PMID- 9251186
TI  - Analysis of xysA, a gene from Streptomyces halstedii JM8 that encodes a 45
      kilodalton modular xylanase, Xys1.
AB  - The gene xysA from Streptomyces halstedii JM8 encodes a protein of 461 amino
      acids (Xys1) which is secreted into the culture supernatant as a protein of 45
      kDa (Xys1L). Later, this form is proteolytically processed after residue D-362 to
      produce the protein Xys1S, which conserves the same xylanolytic activity. The
      cleavage removes a domain of 99 amino acids that shows similarity to bacterial
      cellulose binding domains and that allows the protein Xys1L to bind to
      crystalline cellulose (Avicel). Expression of this monocistronic gene is affected
      by the carbon source present in the culture medium, xylan being the best inducer.
      By using an anti-Xys1L serum, we have been able to detect xylanases similar in
      size to Xys1L and Xys1S in most of the different Streptomyces species analyzed,
      suggesting the ubiquity of these types of xylanases and their processing
      mechanism.

PMID- 9251187
TI  - Use of a promoterless lacZ gene insertion to investigate chitinase gene
      expression in the marine bacterium Pseudoalteromonas sp. strain S9.
AB  - Sequence data for genes encoding 16S rRNA indicated that the marine strain
      previously named Pseudomonas sp. strain S9 would be better identified as a
      Pseudoalteromonas sp. By use of transposon mutagenesis, a chitinase-negative
      mutant of S9 with a lacZ reporter gene insertion was isolated. Part of the
      interrupted gene was cloned and sequenced. The deduced amino acid sequence had
      homology to sequences of bacterial chitinases. Expression of the chitinase gene
      promoter was quantified by measuring the lacZ reporter gene product, beta
      galactosidase, beta-Galactosidase production was induced 10-fold by N
      acetylglucosamine and 3-fold by chitin in minimal medium. Repression of beta
      galactosidase synthesis was observed in rich medium either with or without chitin
      but was not observed in minimal medium containing glucose. The chitinase gene
      promoter was induced by starvation and higher-than-ambient levels of carbon
      dioxide but not by cadmium ion, heat or cold shock, or UV exposure.

PMID- 9251188
TI  - PCR-based approach for detection of novel Bacillus thuringiensis cry genes.
AB  - A two-step strategy, named exclusive PCR or E-PCR, has been developed to overcome
      the main limitation of PCR, which is the detection of already-known sequences
      only. This strategy allows the ability to detect and further clone and sequence
      genes for which no specific primers are available and in which a variable region
      exists between two conserved regions. This approach has been applied to Bacillus
      thuringiensis cryI genes by the use of mixtures of degenerate and specific
      primers recognizing well-known sequences. The first step allows the accurate
      identification of already-characterized cryI genes by the use of three primers.
      During the second step, the same sets of primers are used to exclude known
      sequences and to positively detect cryI genes unrecognized by any specific
      primer. The method, as well as its application to detect, clone, and sequence a
      novel cryIB gene, is described in this article.

PMID- 9251189
TI  - Polyhydroxyalkanoate production in Rhodobacter capsulatus: genes, mutants,
      expression, and physiology.
AB  - Like many other prokaryotes, the photosynthetic bacterium Rhodobacter capsulatus
      produces high levels of polyhydroxyalkanoates (PHAs) when a suitable carbon
      source is available. The three genes that are traditionally considered to be
      necessary in the PHA biosynthetic pathway, phaA (beta-ketothiolase), phaB
      (acetoacetylcoenzyme A reductase), and phaC (PHA synthase), were cloned from
      Rhodobacter capsulatus. In R. capsulatus, the phaAB genes are not linked to the
      phaC gene. Translational beta-galactosidase fusions to phaA and phaC were
      constructed and recombined into the chromosome. Both phaC and phaA were
      constitutively expressed regardless of whether PHA production was induced,
      suggesting that control is posttranslational at the enzymatic level. Consistent
      with this conclusion, it was shown that the R. capsulatus transcriptional
      nitrogen-sensing circuits were not involved in PHA synthesis. The doubling times
      of R. capsulatus transcriptional nitrogen-sensing circuits were not involved in
      PHA synthesis. The doubling times of R. capsulatus grown on numerous carbon
      sources were determined, indicating that this bacterium grows on C2 to C12 fatty
      acids. Grown on acetone, caproate, or heptanoate, wild-type R. capsulatus
      produced high levels of PHAs. Although a phaC deletion strain was unable to
      synthesize PHAs on any carbon source, phaA and phaAB deletion strains were able
      to produce PHAs, indicating that alternative routes for the synthesis of
      substrates for the synthase are present. The nutritional versatility and
      bioenergetic versatility of R. capsulatus, coupled with its ability to produce
      large amounts of PHAs and its genetic tractability, make it an attractive model
      for the study of PHA production.

PMID- 9251190
TI  - Positive selection systems for discovery of novel polyester biosynthesis genes
      based on fatty acid detoxification.
AB  - The photosynthetic bacterium Rhodobacter capsulatus can grow with short- to long
      chain fatty acids as the sole carbon source (R. G. Kranz, K. K. Gabbert, T. A.
      Locke, and M. T. Madigan, Appl. Environ. Microbiol. 63:3003-3009, 1997).
      Concomitant with growth on fatty acids is the production to high levels of the
      polyester storage compounds called polyhydroxyalkanoates (PHAs). Here, we
      describe colony screening and selection systems to analyze the production of PHAs
      in R. capsulatus. A screen with Nile red dissolved in acetone distinguishes
      between PHA producers and nonproducers. Unlike the wild type, an R. capsulatus
      PhaC- strain with the gene encoding PHA synthase deleted is unable to grow on
      solid media containing high concentrations of certain fatty acids. It is proposed
      that this deficiency is due to the inability of the PhaC- strain to detoxify the
      surrounding medium by consumption of fatty acids and their incorporation into
      PHAs. This fatty acid toxicity phenotype is used in selection for the cloning and
      characterization of heterologous phaC genes.

PMID- 9251191
TI  - In vivo recombination between two strains of the genus Nucleopolyhedrovirus in
      its natural host, Spodoptera exigua.
AB  - The DNA restriction map for the enzymes BamHI, BglII, PstI, and XbaI of SeMNPV-US
      (Se-US), the best-studied Nucleopolyhedrovirus strain isolated from Spodoptera
      exigua in California, was used as a reference to construct that of SeMNPV-SP2 (Se
      SP2), a closely related Spanish strain of the same virus. After coinfection of S.
      exigua with both the Se-US and Se-SP2 strains per os, a recombinant virus (SeMNPV
      SUR1 [Se-SUR1]) was detected after one passage which quickly replaced the
      parental viruses. A physical map of Se-SUR1 DNA was constructed for BamHI, BglII,
      PstI, and XbaI and compared to that of the parental viruses, Se-US and Se-SP2. Se
      SUR1 is the result of at least four crossover events between Se-US and Se-SP2 and
      not of selection of a minor variant in one of the parental viruses. Bioassays of
      the recombinant and parental strains against L2 beet armyworm larvae demonstrated
      that their 50% lethal dose values were not significantly different. The
      differences in median lethal time values are too small to explain the replacement
      of the parental viruses by the recombinant virus upon successive passage in vivo,
      although it cannot be ruled out as an explanation for the selective advantage of
      the recombinant strain, Se-SUR1. The consequences of the release of nonindigenous
      or recombinant baculovirus strains in agro-ecosystems are discussed.

PMID- 9251192
TI  - Whole-cell hybridization of Methanosarcina cells with two new oligonucleotide
      probes.
AB  - Two new oligonucleotide probes targeting the 16S rRNA of the methanogenic genus
      Methanosarcina were developed. The probes have the following sequences
      (Escherichia coli numbering): probe SARCI551, 5'-GAC CCAATAATCACGATCAC-3', and
      probe SARCI645, 5'-TCCCGGTTCCAAGTCTGGC-3'. In situ hybridization with the
      fluorescently labelled probes required several modifications of standard
      procedures. Cells of Methanosarcina mazeii S-6 were found to lyse during the
      hybridization step if fixed in 3% formaldehyde and stored in 50% ethanol. Lysis
      was, however, not observed with cells fixed and stored in 1.6% formaldehyde-0.85%
      NaCl. Extensive autofluorescence of the cells was found upon hybridization in the
      presence of 5 mM EDTA, but successful hybridization could be obtained without
      addition of this compound. The mounting agent Citifluor AF1, often used in
      conjugation with the fluorochrome fluorescein, was found to wash the labelled
      probes out of the cells. Stable labelling could be obtained with rhodamine
      labelled probes when the specimen was mounted in immersion oil, and high
      hybridization intensities of the Methanosarcina cells were found even in the
      presence of biomass from an anaerobic reactor. The inherent high autofluorescence
      of the biomass could be lowered by use of a highly specific narrow-band filter.
      The probes were found to be specific for Methanosarcina and useful for detection
      of this genus in samples from anaerobic reactors.

PMID- 9251193
TI  - Diversity and association of psychrophilic bacteria in Antarctic sea ice.
AB  - The bacterial populations associated with sea ice sampled from Antarctic coastal
      areas were investigated by use of a phenotypic approach and a phylogenetic
      approach based on genes encoding 16S rRNA (16S rDNA). The diversity of bacteria
      associated with sea ice was also compared with the bacterial diversity of
      seawater underlying sea ice. Psychrophilic (optimal growth temperature, < or = 15
      degrees C; no growth occurring at 20 degrees C) bacterial diversity was found to
      be significantly enriched in sea ice samples possessing platelet and bottom ice
      diatom assemblages, with 2 to 9 distinct (average, 5.6 +/- 1.8) psychrophilic
      taxa isolated per sample. Substantially fewer psychrophilic isolates were
      recovered from ice cores with a low or negligible population of ice diatoms or
      from under-ice seawater samples (less than one distinct taxon isolated per
      sample). In addition, psychrophilic taxa that were isolated from under-ice
      seawater samples were in general phylogenetically distinct from psychrophilic
      taxa isolated from sea ice cores. The taxonomic distributions of psychrotrophic
      bacterial isolates (optimal growth temperature, > 20 degrees C; growth can occur
      at approximately 4 degrees C) isolated from sea ice cores and under-ice seawater
      were quite similar. Overall, bacterial isolates from Antarctic sea ice were found
      to belong to four phylogenetic groups, the alpha and gamma subdivisions of the
      Proteobacteria, the gram-positive branch, and the Flexibacter-Bacteroides
      Cytophaga phylum. Most of the sea ice strains examined appeared to be novel taxa
      based on phylogenetic comparisons, with 45% of the strains being psychrophilic.
      16S rDNA sequence analysis revealed that psychrophilic strains belonged to the
      genera Colwellia, Shewanella, Marinobacter, Planococcus, and novel phylogenetic
      lineages adjacent to Colwellia and Alteromonas and within the Flexibacter
      Bacteroides-Cytophaga phylum. Psychrotrophic strains were found to be members of
      the genera Pseudoalteromonas, Psychrobacter, Halomonas, Pseudomonas, Hyphomonas,
      Sphingomonas, Arthrobacter, Planococcus, and Halobacillus. From this survey, it
      is proposed that ice diatom assemblages provide niches conducive to the
      proliferation of a diverse array of psychrophilic bacterial species.

PMID- 9251194
TI  - Host-mediated modification of Sau3AI restriction in Listeria monocytogenes:
      prevalence in epidemic-associated strains.
AB  - Most major food-related outbreaks of listeriosis have been traced to a cluster of
      genetically related strains of serovar 4b (epidemic clone). In spite of numerous
      searches, distinct bacteriologic or virulence-related features unique to these
      strains have eluded identification, although a restriction fragment length
      polymorphism (RFLP) characteristic of the epidemic clone has previously been
      described (W. Zheng and S. Kathariou, Appl. Environ. Microbiol. 61:4310-4314,
      1995). We found that DNAs from 75 strains which were derived from three separate
      outbreaks and which had the epidemic clone-specific RFLP were also invariably
      resistant to digestion by Sau3AI and other restriction endonucleases sensitive to
      cytosine methylation at 5' GATC 3' sites. This modification of Sau3AI restriction
      was host mediated, as it did not persist when DNA was cloned and propagated in
      Escherichia coli, and was uncommon among other Listeria strains. Epidemic
      associated strains with this modification were resistant to infection by phage
      propagated in a serotype 4b strain which was not known to be involved in an
      epidemic and which lacked the epidemic clone-specific RFLP. Screening for
      susceptibility to MboI digestion revealed that these epidemic strains lacked
      methylation of adenines at GATC sites. This type of modification was rare among
      Listeria strains and was found in only three (of eight screened) strains of
      serovar 1/2b, possibly representing one clonal lineage.

PMID- 9251195
TI  - Identification and modification of biphenyl dioxygenase sequences that determine
      the specificity of polychlorinated biphenyl degradation.
AB  - The polychlorinated biphenyl (PCB) congener specificities and partial BphA
      sequences of biphenyl dioxygenase were determined for a set of PCB-degrading
      bacteria. The strains examined were categorized into two groups based on their
      ability to degrade 17 PCB congeners. Strains that degraded a broad range of PCBs
      but had relatively weak activity against di-para-substituted PCBs were designated
      as having an LB400-type specificity. Strains designated as having a KF707-type
      specificity degraded a much narrower range of PCBs but had strong activity
      against certain di-para-substituted congeners. BphA protein sequence comparisons
      between these two types of strains identified four regions (designated I, II,
      III, and IV) in which specific sequences were consistently associated with either
      broad or narrow PCB substrate specificity. The dramatic differences in substrate
      specificity between LB400 and KF707 appear to result primarily from a combination
      of mutations in regions III and IV. Altering these regions in the LB400 BphA
      subunit to correspond to those in the KF707 sequence produced a narrow substrate
      specificity very similar to that of KF707. Some individual mutations within
      region III alone were found to improve PCB degradative activity, especially for
      di-para-substituted congeners. However, the greatest improvements in activity
      resulted from multiple amino acid modifications in region III, suggesting that
      the effects of these mutations are cooperative. These results demonstrate the
      ability to significantly improve PCB oxidative activity through sequence
      modifications of biphenyl dioxygenase.

PMID- 9251197
TI  - Characterization of the sediment bacterial community in groundwater discharge
      zones of an alkaline fen: a seasonal study.
AB  - The cell density, activity, and community structure of the bacterial community in
      wetland sediments were monitored over a 13-month period. The study was performed
      at Cedar Bog, an alkaline fen. The objective was to characterize the relationship
      between the sediment bacterial community in groundwater upwelling zones and the
      physical and chemical factors which might influence the community structure and
      activity. DNA, protein, and lipid synthesis were measured at three different
      upwelling zones by using [3H]thymidine, [14C]leucine, and [14C]glucose
      incorporation, respectively. The physiological status (apparent stress) of the
      consortium was assessed by comparing [14C]glucose incorporation into membrane and
      that into storage lipids. Bacterial cell density was determined by acridine
      orange direct counts, and gross bacterial community structure was determined by
      bisbenzimidazole-cesium chloride gradient analysis of total bacterial community
      DNA. Both seasonal and site-related covariation were observed in all estimates of
      bacterial biomass and activity. Growth rate estimates and cell density peaked in
      late July at 2.5 x 10(8) cells/g/day and 2.7 x 10(9) cells/g, respectively, and
      decreased in December to 2.0 x 10(7) cells/g/day and 1.5 x 10(9) cells/g,
      respectively. Across sites, membrane-to-storage-lipid ratios were generally
      highest in late spring and peaked in September for one site. Overall, the data
      indicate dynamic seasonal differences in sediment bacterial community activity
      and physiology, possibly in response to changing physical and chemical
      environmental factors which included the C/N/P ratios of the perfusing
      groundwater. By contrast, total cell numbers were rather constant, and community
      structure analysis indicated that the overall community structure was similar
      throughout the study.

PMID- 9251196
TI  - Evidence for paralytic shellfish poisons in the freshwater cyanobacterium Lyngbya
      wollei (Farlow ex Gomont) comb. nov.
AB  - Lyngbya wollei (Farlow ex Gomont) comb. nov., a perennial mat-forming filamentous
      cyanobacterium prevalent in lakes and reservoirs of the southeastern United
      States, was found to produce a potent, acutely lethal neurotoxin when tested in
      the mouse bioassay. Signs of poisoning were similar to those of paralytic
      shellfish poisoning. As part of the Tennessee Valley Authority master plan for
      Guntersville Reservoir, the mat-forming filamentous cyanobacterium L. wollei, a
      species that had recently invaded from other areas of the southern United States,
      was studied to determine if it could produce any of the known cyanotoxins. Of the
      91 field samples collected at 10 locations at Guntersville Reservoir, Ala., on
      the Tennessee River, over a 3-year period, 72.5% were toxic. The minimum 100%
      lethal doses of the toxic samples ranged from 150 to 1,500 mg kg of lyophilized
      L. wollei cells-1, with the majority of samples being toxic at 500 mg kg-1.
      Samples bioassayed for paralytic shellfish toxins by the Association of Official
      Analytical Chemists method exhibited saxitoxin equivalents ranging from 0 to 58
      micrograms g (dry weight)-1. Characteristics of the neurotoxic compound(s), such
      as the lack of adsorption by C18 solid-phase extraction columns, the short
      retention times on C18 high-performance liquid chromatography (HPLC) columns, the
      interaction of the neurotoxins with saxiphilin (a soluble saxitoxin-binding
      protein), and external blockage of voltage-sensitive sodium channels, led to our
      discovery that this neurotoxin(s) is related to the saxitoxins, the compounds
      responsible for paralytic shellfish poisonings. The major saxitoxin compounds
      thus far identified by comparison of HPLC fluorescence retention times are
      decarbamoyl gonyautoxins 2 and 3. There was no evidence of paralytic shellfish
      poison C toxins being produced by L. wollei. Fifty field samples were placed in
      unialgal culture and grown under defined culture conditions. Toxicity and signs
      of poisoning for these laboratory-grown strains of L. wollei were similar to
      those of the field collection samples.

PMID- 9251198
TI  - Astrovirus survival in drinking water.
AB  - A method based on infection of CaCo-2 cultured cell monolayers (CC) and reverse
      transcription-PCR (RT-PCR) was developed for the specific detection of infectious
      astrovirus. The procedure was validated by titrating poliovirus stocks in
      parallel in CaCo-2 cells by determining the most probable number of
      cytopathogenic units and by cell culture and subsequent RT-PCR (CC-RT-PCR). CC-RT
      PCR was then employed to measure the persistence of astrovirus suspended in
      dechlorinated tap water. After 60 days, the decay of astrovirus infectivity was 2
      log units at 4 +/- 1 degrees C and 3.2 log units at 20 +/- 1 degrees C, while
      after 90 days, the titer reduction was 3.3 and 5 log units at 4 +/- 1 degrees C
      and 20 +/- 1 degrees C, respectively. Astrovirus decay in the presence of free
      chlorine (FC) was monitored by CC-RT-PCR. Residual infectivity was found after 2
      h in the presence of 1 mg of FC/liter. Under these conditions, astrovirus shows a
      log titer reduction (LTR) or 4, while 0.5 mg of FC/liter induced an LTR of 2.4.
      The possibility of acquiring data on the survival of fastidious viruses in the
      environment opens new perspectives on the epidemiology of some significant
      infections transmitted by the fecal-oral route.

PMID- 9251199
TI  - Characterization of Thiobacillus thioparus LV43 and its distribution in a
      chemoautotrophically based groundwater ecosystem.
AB  - Bacterial strain LV43 was previously isolated from a floating microbial mat
      located in Movile Cave, the access point to a chemoautotrophically based
      groundwater ecosystem in southern Romania. This gram-negative, rod-shaped
      organism grows autotrophically through the oxidation of thiosulfate and sulfide,
      but it does not grow heterotrophically. Strain LV43 grows over a pH range of 5.0
      to 9.0, with an optimum near 7.5 at 28 degrees C. The pH of the medium decreased
      from 7.5 to 6.5 during growth on thiosulfate. Carbon isotope fractionation values
      for strain LV43 were within the previously reported range of fractionation values
      for the overall floating microbial mat in Movile Cave and were similar to values
      reported for chemoautotrophic sulfur-oxidizing strains of Thiobacillus
      neapolitanus and Thiomicrospira sp. The 16S rRNA gene sequence of strain LV43 was
      determined, and phylogenetic analysis indicated that strain LV43 was most closely
      related to Thiobacillus thioparus and the uncultured bacterial strain Strip2,
      which is represented by a 16S rRNA clone obtained by direct PCR from the Stripa
      research mine in Sweden. This identification of strain LV43 is supported by its
      G+C content of 62%, which is within the range reported for strains of T.
      thioparus. Fluorescently labeled polyclonal antibodies specific for strain LV43
      were used to locate and enumerate this strain at different locations in Movile
      Cave and in nearby surface-water and groundwater sources. Strain LV43 was found
      only at aerobic, neutral-pH sites within the cave. Strain LV43 was also found
      outside Movile Cave in surface waters and in groundwater believed to intercept
      the same sulfurous aquifer as Movile Cave.

PMID- 9251200
TI  - Immunomagnetic capture PCR to detect viable Cryptosporidium parvum oocysts from
      environmental samples.
AB  - A method to detect viable Cryptosporidium parvum oocysts was developed.
      Polyclonal immunoglobulin G against C. parvum oocyst and sporozoite surface
      antigens was purified from rabbit immune serum, biotinylated, and bound to
      streptoavidin-coated magnetic particles. C. parvum oocysts were captured by a
      specific antigen-antibody reaction and magnetic separation. The oocysts were then
      induced to excyst, and DNA was extracted by heating at 95 degrees C for 10 min. A
      452-bp fragment of C. parvum DNA was amplified by using a pair of C. parvum
      specific primers in PCR. The method detected as few as 10 oocysts in purified
      preparations and from 30 to 100 oocysts inoculated in fecal samples. The
      immunomagnetic capture PCR (IC-PCR) product was identified and characterized by a
      nested PCR that amplified a 210-bp fragment, followed by restriction endonuclease
      digestion of the IC-PCR and nested-PCR products at the StyI site and a
      nonradioactive hybridization using an internal oligonucleotide probe labeled with
      biotin. PCR specificity was also tested, by using DNAs from other organisms as
      templates. In the control experiments, inactivated oocysts were undetectable,
      indicating the ability of this method to differentiate between viable and
      nonviable oocysts. Thus, this system can be used to specifically detect viable C.
      parvum oocysts in environmental samples with great sensitivity, providing an
      efficient way to monitor the environment for C. parvum contamination.

PMID- 9251201
TI  - Identification and detection of Bacillus sporothermodurans spores in 1, 10, and
      100 milliliters of raw milk by PCR.
AB  - A PCR method was developed to detect spores of Bacillus sporothermodurans in 1,
      10, and 100 ml of raw milk. Two primers were derived from a unique sequence after
      subtractive hybridization of B. sporothermodurans DNA with DNA of MB 397, a not
      yet identified spore-forming bacterium isolated from raw milk, closely related to
      B. sporothermodurans. Specific identification was proven on a large collection of
      Bacillus strains and on strains from relevant taxa. The detection of B.
      sporothermodurans in raw milk is based on activation, germination, and outgrowth
      of the spores, followed by PCR identification. Spores from 10 and 100 ml were
      concentrated by centrifugation after chemical extraction of the milk components.
      The total test takes 28 h. The detection limits are 9, 0.4, and 0.22 CFU/ml for
      1, 10, and 100 ml, respectively.

PMID- 9251202
TI  - Molecular ecology of Streptococcus thermophilus bacteriophage infections in a
      cheese factory.
AB  - A mozzarella cheese factory using an undefined, milk-derived Streptococcus
      thermophilus starter system was monitored longitudinally for 2 years to determine
      whether the diversity of the resident bacteriophage population arose from
      environmental sources or from genetic changes in the resident phage in the
      factory. The two hypotheses led to different predictions about the genetic
      diversity of the phages. With respect to host range, 12 distinct phage types were
      observed. With two exceptions, phages belonging to different lytic groups showed
      clearly distinct restriction patterns and multiple isolates of phages showing the
      same host range exhibited identical or highly related restriction patterns.
      Sequencing studies in a conserved region of the phage genome revealed no point
      mutations in multiple isolates of the same phage type, while up to 12% nucleotide
      sequence diversity was observed between the different phage types. This diversity
      is as large as that between the most different sequences from phages in our
      collection. These observations make unlikely a model that postulates a single
      phage invasion event and diversification of the phage during its residence in the
      factory. In the second stage of our factory study, a defined starter system was
      introduced that could not propagate the resident factory phage population. Within
      a week, three new phage types were observed in the factory while the resident
      phage population was decreased but not eliminated. Raw milk was the most likely
      source of these new phages, as phages with identical host ranges and restriction
      patterns were isolated from raw milk delivered to the factory during the
      intervention trial. Apparently, all of the genetic diversity observed in the S.
      thermophilus phages isolated during our survey was already created in their
      natural environment. A better understanding of the raw-milk ecology of S.
      thermophilus phages is thus essential for successful practical phage control.

PMID- 9251203
TI  - Characterization of the gene encoding an extracellular laccase of Myceliophthora
      thermophila and analysis of the recombinant enzyme expressed in Aspergillus
      oryzae.
AB  - A genomic DNA segment encoding an extracellular laccase was isolated from the
      thermophilic fungus Myceliophthora thermophila, and the nucleotide sequence of
      this gene was determined. The deduced amino acid sequence of M. thermophila
      laccase (MtL) shows homology to laccases from diverse fungal genera. A vector
      containing the M. thermophila laccase coding region, under transcriptional
      control of an Aspergillus oryzae alpha-amylase gene promoter and terminator, was
      constructed for heterologous expression in A. oryzae. The recombinant laccase
      expressed in A. oryzae was purified to electrophoretic homogeneity by anion
      exchange chromatography. Amino-terminal sequence data suggests that MtL is
      synthesized as a preproenzyme. The molecular mass was estimated to be
      approximately 100 to 140 kDa by gel filtration on Sephacryl S-300 and to be 85
      kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Carbohydrate
      analysis revealed that MtL contains 40 to 60% glycosylation. The laccase shows an
      absorbance spectrum that is typical of blue copper oxidases, with maxima at 276
      and 589 nm, and contains 3.9 copper atoms per subunit. With syringaldazine as a
      substrate, MtL has optimal activity at pH 6.5 and retains nearly 100% of its
      activity when incubated at 60 degrees C for 20 min. This is the first report of
      the cloning and heterologous expression of a thermostable laccase.

PMID- 9251204
TI  - Separation of bacterial cells by isoelectric focusing, a new method for analysis
      of complex microbial communities.
AB  - A simple isoelectric focusing (IEF) method for whole bacterial cells was
      developed. In a pH gradient of 2 to 10 and an electric field of 11.5 V cm-1,
      mixtures of cells from the three different bacterial strains Chlorobium limicola
      6230, Pseudomonas stutzeri DSM 50227, and Micrococcus luteus DSM 20030 could be
      separated. A density gradient of Ficoll prevented convective currents in the
      system. The method was tested with a concentrated mixture of bacteria from a
      shallow eutrophic lake and yielded up to 10 different bands. Species composition
      in each IEF band was analyzed by PCR plus denaturing gradient gel electrophoresis
      (DGGE). Each IEF band exhibited a different species composition. After the
      separation of cells by IEF three times more 16S ribosomal DNA signals could be
      detected by DGGE than in the unfractionated natural bacterial community. It is
      concluded that the resolution of these molecular biological methods is
      significantly enhanced if cells are first separated by IEF. At the same time, the
      IEF fractions are enriched for certain species, which can be used in subsequent
      cultivation experiments.

PMID- 9251205
TI  - Physiological and biochemical characterization of Trichoderma harzianum, a
      biological control agent against soilborne fungal plant pathogens.
AB  - Monoconidial cultures of 15 isolates of Trichoderma harzianum were characterized
      on the basis of 82 morphological, physiological, and biochemical features and 99
      isoenzyme bands from seven enzyme systems. The results were subjected to
      numerical analysis which revealed four distinct groups. Representative sequences
      of the internal transcribed spacer 1 (ITS 1)-ITS 2 region in the ribosomal DNA
      gene cluster were compared between groups confirming this distribution. The
      utility of the groupings generated from the morphological, physiological, and
      biochemical data was assessed by including an additional environmental isolate in
      the electrophoretic analysis. The in vitro antibiotic activity of the T.
      harzianum isolates was assayed against 10 isolates of five different soilborne
      fungal plant pathogens: Aphanomyces cochlioides, Rhizoctonia solani, Phoma betae,
      Acremonium cucurbitacearum, and Fusarium oxysporum f. sp. radicis lycopersici.
      Similarities between levels and specificities of biological activity and the
      numerical characterization groupings are both discussed in relation to antagonist
      specific populations in known and potential biocontrol species.

PMID- 9251206
TI  - Comparative sensitivities of Sabin and Mahoney poliovirus type 1 prototype
      strains and two recent isolates to low concentrations of glutaraldehyde.
AB  - Significant intratypic differences in the glutaraldehyde (GTA) sensitivity of
      echovirus isolates have been shown. While exploring ways to optimize the study of
      GTA sensitivity of enteroviruses, we also observed intratypic differences in
      poliovirus type 1 isolates collected in France. A suspension procedure was used
      for assessing the virucidal effect of GTA at low concentrations (< or = 0.10%)
      against purified viruses. Two recent isolates of poliovirus type 1 tested were
      first fully characterized by the PCR restriction fragment length polymorphism
      (RFLP) test. The RFLP pattern of clinical isolate 5617 was similar to that of
      poliovirus type 1 LS-c, 2ab (Sabin strain), confirming the vaccine origin of
      strain 5617. The RFLP pattern of strain 5915 recovered from sewage was different
      from that of the Mahoney strain, suggesting a genetic variation in this wild
      isolate. We then analyzed under the same controlled conditions the GTA
      sensitivities of both isolates and their respective prototype strains. The wild
      Mahoney and 5915 strains exhibited significantly lower sensitivities to GTA than
      did the vaccine Sabin and 5617 strains. The inactivation rates of clinical
      isolates 5617 and 5915 were very similar to those of their corresponding
      reference Sabin and Mahoney strains. Both the conformational structure of the
      capsid of each strain and the amino acid constitution of structural polypeptides
      could be involved in the variations observed. The relevance of our comparative
      sensitivity studies to standardization of virucidal tests is discussed.

PMID- 9251207
TI  - Reduction of aerobic acetate production by Escherichia coli.
AB  - Acetate excretion by Escherichia coli during aerobic growth on glucose is a major
      obstacle to enhanced recombinant protein production. We report here that the
      fraction of carbon flux through the anaplerotic pathways is one of the factors
      influencing acetate excretion. Flux analysis of E. coli central metabolic
      pathways predicts that increasing the fraction of carbon flux through the
      phosphoenolpyruvate carboxylase (PPC) pathway and the glyoxylate bypass reduces
      acetate production. We tested this prediction by overexpressing PPC and
      deregulating the glyoxylate bypass by using a fadR strain. Results show that the
      acetate yield by the fadR strain with PPC overexpression is decreased more than
      fourfold compared to the control, while the biomass yield is relatively
      unaffected. Apparently, the fraction of carbon flux through the anaplerotic
      pathways is one of the factors that influence acetate excretion. These results
      confirm the prediction of our flux analysis and further suggest that E. coli is
      not fully optimized for efficient utilization of glucose.

PMID- 9251208
TI  - The methanol dehydrogenase structural gene mxaF and its use as a functional gene
      probe for methanotrophs and methylotrophs.
AB  - The methanol dehydrogenase gene mxaF, encoding the large subunit of the enzyme,
      was amplified from the DNA of a number of representative methanotrophs,
      methyletrophs, and environmental samples by PCR using primers designed from
      regions of conserved amino acid sequence identified by comparison of three known
      sequences of the large subunit of methanol dehydrogenase. The resulting 550-bp
      PCR products were cloned and sequenced. Analysis of the predicted amino acid
      sequences corresponding to these mxaF genes revealed strong sequence
      conservation. Of the 172 amino acid residues, 47% were conserved among all 22
      sequences obtained in this study. Phylogenetic analysis of these MxaF sequences
      showed that those from type I and type II methanotrophs form two distinct
      clusters and are separate from MxaF sequences of other gram-negative
      methylotrophs. MxaF sequences retrieved by PCR from DNA isolated from a blanket
      bog peat core sample formed a distinct phylogenetic cluster within the MxaF
      sequences of type II methanotrophs and may originate from a novel group of
      acidophilic methanotrophs which have yet to be cultured from this environment.

PMID- 9251209
TI  - Effects of several factors on the heat-shock-induced thermotolerance of Listeria
      monocytogenes.
AB  - The influence of the temperature at which Listeria monocytogenes had been grown
      (4 or 37 degrees C) on the response to heat shocks of different durations at
      different temperatures was investigated. For cells grown at 4 degrees C, the
      effect of storage, prior to and after heat shock, on the induced thermotolerance
      was also studied. Death kinetics of heat-shocked cells is also discussed. For L.
      monocytogenes grown at 37 degrees C, the greatest response to heat shock was a
      fourfold increase in thermotolerance. For L. monocytogenes grown at 4 degrees C,
      the greatest response to heat shock was a sevenfold increase in thermotolerance.
      The only survival curves of cells to have shoulders were those for cells that had
      been heat shocked. A 3% concentration of sodium chloride added to the recovery
      medium made these shoulders disappear and decreased decimal reduction times. The
      percentage of cells for which thermotolerance increased after a heat shock was
      smaller the milder the heat shock and the longer the prior storage.

PMID- 9251211
TI  - Phosphorus and bacterial growth in drinking water.
AB  - The availability of organic carbon is considered the key factor to regulate
      microbial regrowth in drinking water network. However, boreal regions (northern
      Europe, Russia, and North America) contain a large amount of organic carbon in
      forests and peatlands. Therefore, natural waters (lakes, rivers, and groundwater)
      in the northern hemisphere generally have a high content of organic carbon. We
      found that microbial growth in drinking water in Finland is highly regulated not
      only by organic carbon but also by the availability of phosphorus. Microbial
      growth increased up to a phosphate concentration of 10 micrograms of PO4-P liter
      1. Inorganic elements other than phosphorus did not affect microbial growth in
      drinking water. This observation offers novel possibilities to restrict microbial
      growth in water distribution systems by developing technologies to remove
      phosphorus efficiently from drinking water.

PMID- 9251210
TI  - Analysis of actinomycete communities by specific amplification of genes encoding
      16S rRNA and gel-electrophoretic separation in denaturing gradients.
AB  - A group-specific primer, F243 (positions 226 to 243, Escherichia coli numbering),
      was developed by comparison of sequences of genes encoding 16S rRNA (16S rDNA)
      for the detection of actinomycetes in the environment with PCR and temperature or
      denaturing gradient gel electrophoresis (TGGE or DGGE, respectively). The
      specificity of the forward primer in combination with different reverse ones was
      tested with genomic DNA from a variety of bacterial strains. Most actinomycetes
      investigated could be separated by TGGE and DGGE, with both techniques giving
      similar results. Two strategies were employed to study natural microbial
      communities. First, we used the selective amplification of actinomycete sequences
      (E. coli positions 226 to 528) for direct analysis of the products in denaturing
      gradients. Second, a nested PCR providing actinomycete-specific fragments (E.
      coli positions 226 to 1401) was used which served as template for a PCR when
      conserved primers were used. The products (E. coli positions 968 to 1401) of this
      indirect approach were then separated by use of gradient gels. Both approaches
      allowed detection of actinomycete communities in soil. The second strategy
      allowed the estimation of the relative abundance of actinomycetes within the
      bacterial community. Mixtures of PCR-derived 16S rDNA fragments were used as
      model communities consisting of five actinomycetes and five other bacterial
      species. Actinomycete products were obtained over a 100-fold dilution range of
      the actinomycete DNA in the model community by specific PCR; detection of the
      diluted actinomycete DNA was not possible when conserved primers were used. The
      methods tested for detection were applied to monitor actinomycete community
      changes in potato rhizosphere and to investigate actinomycete diversity in
      different soils.

PMID- 9251212
TI  - Two groups of bacteriophages infecting Streptococcus thermophilus can be
      distinguished on the basis of mode of packaging and genetic determinants for
      major structural proteins.
AB  - A comparative study of 30 phages of Streptococcus thermophilus was performed
      based on DNA restriction profiles, DNA homology, structural proteins, packaging
      mechanisms, and host range data. All phages exhibited distinct DNA restriction
      profiles, with some phages displaying similarly sized restriction fragments. DNA
      homology was shown to be present among all 30 phages. The phages could be divided
      into two groups on the basis of their packaging mechanism as was derived from the
      appearance of submolar DNA fragments in restriction enzyme digests and the
      presence (cos-containing phages) or absence (pac-containing phages) of cohesive
      genomic extremities. Interestingly, the 19 identified cos-containing phages
      possessed two major structural proteins (32 and 26 kDa) in contrast to the
      remaining 11 pac-containing phages, which possessed three major structural
      proteins (41, 25, and 13 kDa). Southern hybridization demonstrated that all pac
      containing phages tested contain homologs of the genes encoding the three major
      structural proteins of the pac-containing phage O1205, whereas all cos-containing
      phages tested exhibit homology to the gene specifying one of the structural
      components of the cos-containing phage phi 7201. Fifty-seven percent of the
      phages (both cos and pac containing) possessed the previously identified 2.2-kb
      EcoRI fragment of the temperate S. thermophilus phage Sfi18 (H. Brussow, A.
      Probst, M. Fremont, and J. Sidoti, Virology 200:854-857, 1994). No obvious
      correlation was detected between grouping based on packaging mechanism and host
      range data obtained with 39 industrial S. thermophilus strains.

PMID- 9251213
TI  - Cloning and characterization of a cytolytic and mosquitocidal delta-endotoxin
      from Bacillus thuringiensis subsp. jegathesan.
AB  - A cytolytic toxin gene encoding a 30.1-kDa Cyt2Bb1 toxin protein from B.
      thuringiensis subsp. jegathasan was cloned employing a limited-growth PCR
      screening method with forward and reverse oligonucleotide primers designed from N
      terminal amino acid sequences of native and trypsin-cleaved protein,
      respectively. The expressed protein showed little cross-reactivity to the
      antibody raised against the Cyt1Aa protein. Unlike Cyt1Aa and Cyt2Aa expression,
      there was little or no visible crystal inclusion formation under microscopic
      observation. The amino acid sequence alignment indicated 31 and 66% identity to
      Cyt1Aa and Cyt2Aa, respectively. The sequence alignment for five known cytolytic
      proteins indicated three highly conserved regions, two in the loop regions
      between alpha-helices and beta-sheets and one in the loop region between beta
      sheets 5 and 6. beta-Blocks 4 to 7 are also conserved, not only structurally but
      also among the amino acids in the hydrophobic faces. Mosquitocidal activity
      assays indicated that the Cyt2Bb toxin had less toxicity than Cyt1Aa and had
      about 600-times-lower toxicity than the wild-type whole toxin crystal. However,
      both the Cyt2Bb and the Cyt1Aa toxin showed comparable levels of hemolytic
      activity.

PMID- 9251214
TI  - Quantitative fluorescence in situ hybridization of Aureobasidium pullulans on
      microscope slides and leaf surfaces.
AB  - A 21-mer oligonucleotide probe designated Ap665, directed at the 18S rRNA of
      Aureobasidium pullulans and labelled with five molecules of fluorescein
      isothiocyanate, was applied by fluorescence in situ hybridization (FISH) to
      populations of the fungus on slides and apple leaves from growth chamber
      seedlings and orchard trees. In specificity tests that included Ap665 and a
      similarly labelled universal probe and the respective complementary probes as
      controls, the hybridization signal was strong for Ap665 reactions with 12 A.
      pullulans strains but at or below background level for 98 other fungi including
      82 phylloplane isolates. Scanning confocal laser microscopy was used to confirm
      that the fluorescence originated from the cytoplasmic matrix and to overcome
      limitations imposed on conventional microscopy by leaf topography. Images were
      recorded with a cooled charge-coupled device video camera and digitized for
      storage and manipulation. Image analysis was used to verify semiquantitative
      fluorescence ratings and to demonstrate how the distribution of the fluorescence
      signal in specific interactions (e.g., Ap665 with A. pullulans cells) could be
      separated at a given probability level from nonspecific fluorescence (e.g., in
      interactions of Ap665 with Cryptococcus laurentii cells) of an overlapping
      population. Image analysis methods were used also to quantify epiphytic A.
      pullulans populations based on cell number or percent coverage of the leaf
      surface. Under some conditions, leaf autofluorescence and the release of
      fluorescent compounds by leaves during the processing for hybridization decreased
      the signal-to-noise ratio. These effects were reduced by the use of appropriate
      excitation filter sets and fixation conditions. We conclude that FISH can be used
      to detect and quantify A. pullulans cells in the phyllosphere.

PMID- 9251215
TI  - Improved sensitivity of whole-cell hybridization by the combination of
      horseradish peroxidase-labeled oligonucleotides and tyramide signal
      amplification.
AB  - The substrate fluorescein-tyramide was combined with oligonucleotide probes
      directly labeled with horseradish peroxidase to improve the sensitivity of in
      situ hybridization of whole fixed bacterial cells. Flow cytometry and
      quantitative microscopy of cells hybridized by this technique showed 10- to 20
      fold signal amplifications relative to fluorescein-monolabeled probes. The
      application of the new technique to the detection of natural bacterial
      communities resulted in very bright signals; however, the number of detected
      cells was significantly lower than that detected with fluorescently monolabeled,
      rRNA-targeted oligonucleotide probes.

PMID- 9251216
TI  - Three of the seven bphC genes of Rhodococcus erythropolis TA421, isolated from a
      termite ecosystem, are located on an indigenous plasmid associated with biphenyl
      degradation.
AB  - Rhodococcus erythropolis TA421, a polychlorinated biphenyl and biphenyl degrader
      isolated from a termite ecosystem, has seven bphC genes expressing 2,3
      dihydroxybiphenyl dioxygenase activity. R. erythropolis TA421 harbored a large
      and probably linear plasmid on which three (bphC2, bphC3, and bphC4) of the seven
      bphC genes were located. A non-biphenyl-degrading mutant, designated strain
      TA422, was obtained spontaneously from R. erythropolis TA421. TA422 lacked the
      plasmid, suggesting that the three bphC genes were involved in the degradation of
      biphenyl. Southern blot analyses showed that R. erythropolis TA421 and
      Rhodococcus globerulus P6 have a similar set of bphC genes and that the genes for
      biphenyl catabolism are located on plasmids of different sizes. These results
      indicated that the genes encoding the biphenyl catabolic pathway in Rhodococcus
      strains are borne on plasmids.

PMID- 9251217
TI  - Glutathione S-transferase-encoding gene as a potential probe for environmental
      bacterial isolates capable of degrading polycyclic aromatic hydrocarbons.
AB  - Homologs of the glutathione S-transferase (GST)-encoding gene were identified in
      a collection of aromatic hydrocarbon-degrading Sphingomonas spp. isolated from
      New Zealand, Antarctica, and the United States by using PCR primers designed from
      the GST-encoding gene of Sphingomonas paucimobilis EPA505. Sequence analysis of
      PCR fragments generated from these isolates and of the GST gene amplified from
      DNA extracted from polycyclic aromatic hydrocarbon (PAH)-contaminated soil
      revealed a high degree of conservation, which may make the GST-encoding gene a
      potentially useful marker for PAH-degrading bacteria.

PMID- 9251218
TI  - Cell-density-dependent sensitivity of a mer-lux bioassay.
AB  - The sensitivity of a previously described assay (O. Selifonova, R. Burlage, and
      T. Barkay, Appl. Environ. Microbiol. 59:3083-3090, 1993) for the detection of
      bioavailable inorganic mercury (Hg2+) by the activation of a mer-lux fusion was
      increased from nanomolar to picomolar concentrations by reducing biomass in the
      assays from 10(7) to 10(5) cells ml-1. The increase in sensitivity was due to a
      reduction in the number of cellular binding sites that may compete with the
      regulatory protein, MerR, for binding of the inducer, Hg2+. These results show
      that (i) the sensitivity of the mer-lux assay is sufficient for the detection of
      Hg2+ in most contaminated natural waters and (ii) mer-specified reactions, Hg2+
      reduction and methylmercury degradation, can be induced in natural waters and may
      participate in the geochemical cycling of mercury.

PMID- 9251220
TI  - Interference of peptone and tyrosine with the lignin peroxidase assay.
AB  - The N-unregulated white rot fungus Bjerkandera sp. strain BOS55 was cultured in 1
      liter of peptone-yeast extract medium to produce lignin peroxidase (LiP). During
      the LiP assay, the oxidation of veratryl alcohol to veratraldehyde was inhibited
      due to tyrosine present in the peptone and the yeast extract.

PMID- 9251219
TI  - Expression and secretion of a thermostable bacterial xylanase in Kluyveromyces
      lactis.
AB  - The xynA structural gene from the extremely thermophilic anaerobe Dictyoglomus
      thermophilum Rt46B.1 was fused in frame with the secretion signal of the
      Kluyveromyces lactis killer toxin in episomal expression vectors based on the
      Kluyveromyces plasmid pKD1. XynA was secreted predominantly as an unglycosylated
      35-kDa protein which comprised up to 90% of the total extracellular proteins and
      reached a concentration of 130 micrograms/ml in shake-flask cultures grown under
      selective conditions.

PMID- 9251221
TI  - Thermal-death times of opaque and translucent morphotypes of Vibrio vulnificus.
AB  - Thermal-death times were determined for Vibrio vulnificus strains with different
      morphotypes. Opaque strains showed higher D values (times required to reduce the
      viable population of a given strain by 90%) than translucent strains. Z values
      (absolute values of the temperature required to reduce 1 log scale of D values)
      were also significantly higher in opaque morphotypes (2.4 to 2.5 degrees C) than
      in translucent ones (1.7 to 2.1 degrees C). These results indicate that the
      morphotype is related to the organism's susceptibility to heat.

PMID- 9251222
TI  - Linear mitochondrial plasmids of Fusarium oxysporum contain genes with sequence
      similarity to genes encoding a reverse transcriptase from Neurospora spp.
AB  - Two linear mitochondrial plasmids called pFOXC1 and pFOXC2 from the fungus
      Fusarium oxysporum were previously described. DNA sequence comparisons indicated
      that the derived amino acid sequences of both plasmids exhibit similarity to the
      reverse transcriptase of the Mauriceville and Varkud plasmids of Neurospora spp.
      The derived amino acid sequence of pFOXC2 has 51% similarity and 32% identity to
      the Neurospora reverse transcriptase; sequence similarity was greatest for seven
      blocks of amino acids that are conserved in reverse transcriptases from a wide
      range of biological sources. Northern analysis suggests that full-length RNAs
      corresponding to the plasmids are found in representative isolates.

PMID- 9251223
TI  - Glutamate dehydrogenase activity profiles for type strains of ruminal Prevotella
      spp.
AB  - The glutamate dehydrogenase (GDH) activities for the type strains of Prevotella
      ruminicola (strain 23), Prevotella brevis (strain GA33), and Prevotella bryantii
      (strain B(1)4) were assessed by a combination of enzyme assays and analysis of
      migration patterns of GDH proteins following nondenaturing polyacrylamide gel
      electrophoresis. Unlike results with most other prokaryotes, but similar to
      results with other members of the family Bacteroidaceae, NADPH-utilizing specific
      activity was greatest in all species following ammonia-limited growth. Similar
      also to previous findings with P. bryantii, the NAD(P)H-utilizing GDH activity of
      P. ruminicola can be attributed to a single protein. However, P. brevis produces
      an additional GDH protein(s) in response to growth with peptides. These results
      conclusively demonstrate that all type strains of the ruminal Prevotella sp.
      grouping possess GDH activity.

PMID- 9251224
TI  - Effect of alum on free-living and copepod-associated Vibrio cholerae O1 and O139.
AB  - The effects of alum [KAl(SO4)2] on free-living and copepod-associated Vibrio
      cholerae O1 and O139 were investigated by using plate counts and
      immunofluorescence direct viable counting (DVC). Growth of alum-treated cells in
      0.5/1000 Instant Ocean seawater was inhibited, i.e., no growth was obtained on
      Luria-Bertani (LB) agar or thiosulfate-citrate-bile salt-sucrose (TCBS) agar.
      However, a significant number of the inhibited cells maintained viability, as
      measured by DVC. In comparison, a significant number of V. cholerae organisms
      associated with zooplankton, most of which were crustacean copepods, were viable
      but nonculturable, with only a small number of cells retaining culturability on
      LB and TCBS agar. Both DVC and viable plate counts (CFU) were significantly
      greater for V. cholerae O1 and O139 associated with zooplankton than for V.
      cholerae in water alone, i.e., without copepods. It is concluded that alum is an
      effective coagulant but not an effective killing agent for V. cholerae and that
      association with copepods offers protection for V. cholerae O1 and O139 against
      alum and chlorine treatments.

PMID- 9251225
TI  - PCR primers to amplify 16S rRNA genes from cyanobacteria.
AB  - We developed and tested a set of oligonucleotide primers for the specific
      amplification of 16S rRNA gene segments from cyanobacteria and plastids by PCR.
      PCR products were recovered from all cultures of cyanobacteria and diatoms that
      were checked but not from other bacteria and archaea. Gene segments selectively
      retrieved from cyanobacteria and diatoms in unialgal but nonaxenic cultures and
      from cyanobionts in lichens could be directly sequenced. In the context of
      growing sequence databases, this procedure allows rapid and phylogenetically
      meaningful identification without pure cultures or molecular cloning. We
      demonstrate the use of this specific PCR in combination with denaturing gradient
      gel electrophoresis to probe the diversity of oxygenic phototrophic
      microorganisms in cultures, lichens, and complex microbial communities.

PMID- 9251226
TI  - Reductive dehalogenation of halocarboxylic acids by the phototrophic genera
      Rhodospirillum and Rhodopseudomonas.
AB  - Type strains of the purple nonsulfur species Rhodospirillum rubrum,
      Rhodospirillum photometricum, and Rhodopseudomonas palustris grew
      phototrophically on a number of two- and three-carbon halocarboxylic acids in the
      presence of CO2, by reductive dehalogenation and assimilation of the resulting
      acid. Strains of each of these species were able to grow on chloroacetic, 2
      bromopropionic, 2-chloropropionic, and 3-chloropropionic acids at a concentration
      of 2 mM. Only R. palustris DSM 123 was able to grow on bromoacetic acid and then
      only at a reduced concentration of 1 mM. R. palustris ATCC 33872 (formerly R.
      rutila) was unable to grow on any of the substrates tested. The ability of these
      organisms to utilize halocarboxylic acids indicates that they may have a
      significant role to play in the removal of these environmental pollutants from
      illuminated anaerobic habitats such as lakes, waste lagoons, sediments of ditches
      and ponds, mud, and moist soil.

PMID- 9251228
TI  - Basic issues in forensic DNA typing.
AB  - DNA analysis has become the standard method in forensic stain typing (termed DNA
      profiling). In contrast to conventional serological methods, any human tissue or
      body fluid can be analysed by DNA profiling as long as it contains nucleated
      cells. The majority of genetic systems studied at the DNA level are derived from
      "non-coding" portions from the human genome, and are located either in the
      vicinity of expressed (coding) genes or in stretches of DNA sequences
      interspersing with the genes. The typing results are usually recorded as DNA
      fragment lengths or "alleles" indicating the number of core repeat elements for
      short tandem repeat systems. These typing results do not contain any useful
      information which might reveal genetic traits or predispositions for inherited
      disease about the individual studied. Typing systems for DNA profiling are
      predominantly selected according to criteria related to the robustness for typing
      of (potentially degraded) forensic specimens, the degree of genetic polymorphism
      (which influences the chance to exclude a wrongfully accused person), and the
      amenability to standardisation as a basis to obtain reproducible results.

PMID- 9251229
TI  - Fatal occlusion of the left coronary main stem by a fragment from the femoral
      artery: a previously unreported complication of cardiac catheterization.
AB  - A 59-year-old man with grade III angina pectoris and 80% stenosis of the left
      anterior descending coronary artery developed an acute total occlusion of the
      artery during percutaneous transluminal coronary angioplasty (PTCA). Attempts at
      recanalisation and resuscitation were ineffective, and the patient died. The
      medico-legal autopsy revealed obstruction of left main coronary artery by a
      ringshaped piece of arterial wall that had been torn out of the femoral artery at
      the punction site and driven around the tip of the catheter into the orifice of
      the left coronary artery, filling it. This kind of complication of PTCA has not
      been described previously.

PMID- 9251227
TI  - Cloning and expression of an endo-1,3-1,4-beta-glucanase gene from Bacillus
      macerans in Lactobacillus reuteri.
AB  - Strains of the gastrointestinal species Lactobacillus reuteri were
      electrotransformed with plasmid constructs containing the endo-1,3-1,4-beta
      glucanase gene (bglM) of Bacillus macerans. The enzyme was expressed and secreted
      by the lactobacilli. A plasmid construct containing the bglM gene lacking its
      promoter was derived and was demonstrated to be useful as a promoter probe
      vector.

PMID- 9251230
TI  - Gas chromatographic examination of postmortem specimens after maprotiline
      intoxication.
AB  - Ingestion of an unknown quantity of Ludiomil (maprotiline)-costed tablets in a
      suicide is described. Although maprotiline is known for over 20 years now,
      relatively few cases of intoxications due to maprotiline overdose have been
      reported. The authors report a new and quick method to analyze and determine
      maprotiline and N-desmethylmaprotiline concentration in body fluids and
      postmortem specimens. The analytes and an internal standard (amitriptyline) were
      extracted from alkalinized samples into ethyl acetate before GC-NPD analysis. The
      proposed method resulted in a rapid procedure most useful in cases of deliberate
      poisoning with the tetracyclic antidepressant drug Ludiomil.

PMID- 9251231
TI  - Rapid analysis of malathion in blood using head space-solid phase microextraction
      and selected ion monitoring.
AB  - A simple and rapid method for analysis of malathion in blood was developed using
      head space-solid phase microextraction (HS-SPME) and gas chromatography mass
      spectrometry/ electron impact ionization-selected ion monitoring (GC-MS/EI-SIM).
      A vial containing a blood sample, ammonium sulphate, sulphuric acid and
      fenitrothion as an internal standard, was heated at 90 degrees C for 15 min. The
      extraction fiber of the SPME was exposed for 5 min in the head space of the vial.
      The compounds absorbed on the fiber were detached by exposing the fibre in the
      injection port of GC-MS. A straight calibration curve was obtained between
      malathion concentrations of 2.5 to 50.0 micrograms g-1 in blood. No interfering
      substances were found, and the time for analysis was 40 min for one sample.

PMID- 9251232
TI  - Gas chromatographic/mass spectrometric determination of lysergic acid
      diethylamide (LSD) in serum samples.
AB  - A sensitive method for the detection and quantification of lysergic acid
      diethylamide (LSD) in serum samples is described. After liquid-liquid extraction
      the trimethylsilyl derivative of LSD is detected by gas chromatography-mass
      spectrometry. Experiments with spiked samples resulted in a recovery of 76%, the
      coefficient of variation was 9.3%. Excellent linearity was obtained over the
      range 0.1-10 ng ml-1. Additionally experiments demonstrating the light
      sensitivity of LSD are presented together with casuistics.

PMID- 9251233
TI  - Bacterial toxins and sudden unexpected death in a young child.
AB  - The sudden unexpected death of a six year old child following an upper
      respiratory tract infection is reported. Laboratory investigations revealed the
      presence of staphylococcal toxic shock syndrome toxin-1 (TSST-1) in samples of
      brain tissue. The significance of this finding is discussed.

PMID- 9251234
TI  - Site of entrance wound and direction of bullet path in firearm fatalities as
      indicators of homicide versus suicide.
AB  - In a retrospective study, 288 firearm deaths were analysed to identify factors
      indicating homicide. The cases were classified as suicides (213), homicides (54),
      accidents (14) and undetermined cases (7). A number of factors, related to the
      circumstances and the autopsy findings, were studied. Whereas 41% of the homicide
      victims were females, women only constituted 1.4% of the suicide victims. The
      mean age was 37 and 50 years among homicide and suicide victims, respectively.
      Most suicides were committed at or in the vicinity of the residence, whereas a
      majority of the homicides occurred elsewhere. The majority of the suicide victims
      had either left a suicide note or had medical records of previous psychiatric
      illness. In all groups, shotguns were the most frequent weapon used. Fifty-seven
      percent of the homicide victims, but only three percent of the suicide victims
      had sustained more than one gunshot wound. One-third of the homicide victims were
      shot at close range. Alcohol was present in one-third of both homicide and
      suicide victims. Whereas 38% of the homicidal gunshot wounds had their entrances
      at anatomical regions typical of suicide, the direction of the bullet path often
      differed from the directions recorded in suicides. Hence, in this material, an
      entrance wound in the right temple indicated suicide, but in combination with a
      direction back-to-front, the wound was more likely to be homicidal. This study
      suggests that an estimation of the direction of the internal bullet path should
      be conducted in firearm fatalities, and that this factor may assist in the
      determination of the manner of death.

PMID- 9251235
TI  - Detection of white restorative dental materials using an alternative light
      source.
AB  - We assessed the value of an alternative light source for detecting white
      composite dental materials in burned and unburned teeth. Teeth filled with 18
      different restorative materials (composite, glass ionomer or hybrid composite),
      were viewed with a Polilight. Between 415 nm and 555 nm, the glass ionomers
      showed distinctly different optical properties from the other materials: they
      either fluoresced or appeared darker. Wavelengths 415 nm to 530 nm gave a general
      enhancement in composite detection (17 of 18 materials). Light above 590 nm was
      of little value, enhancing detection in only 2 of 18 materials. After simulated
      burning of the teeth, there was enhanced visibility of 8 of 18 materials at
      wavelengths under 350 nm. Burning destroyed the previously distinct optical
      properties of the glass ionomers. Overall, this alternative light source aids the
      identification of white composite dental materials and could be used in routine
      forensic odontology practice.

PMID- 9251236
TI  - Analysis of mortality reports from a university hospital of Turkey.

PMID- 9251237
TI  - Heparan sulphate.
AB  - Heparan sulphates, the N-sulphated polysaccharides components of proteoglycans,
      are common constituents of cell surfaces and the extracellular matrix. The
      heparan sulphate polysaccharide chain has a unique molecular design in the which
      the clusters of N- and O-sulphated sugar residues, separated by regions of low
      sulphation, determine specific protein binding properties. The heparan sulphate
      chains are attached to various protein cores, which determine the location of the
      proteoglycan in the cell membrane and extracellular matrix. The diverse functions
      of heparan sulphate, which range from the control of blood coagulation to the
      regulation of cell growth and adhesion, depend on the capacity of the chains to
      activate protein ligands, such as antithrombin III and members of the fibroblast
      growth factor family. These properties are currently being exploited in the
      development of synthetic heparan sulphates as anticoagulants and promoters of
      wound healing. Conversely organic mimics of growth factor activating saccharides
      could possibly be designed to suppress tumour growth and prevent restenosis after
      coronary vessel angioplasty.

PMID- 9251238
TI  - Cathepsin B.
AB  - Cathepsin B is a lysosomal cysteine protease of the papain family. It functions
      in intracellular protein catabolism and in certain situations may also be
      involved in other physiological processes, such as processing of antigens in the
      immune response, hormone activation and bone turnover. There is also evidence
      that cathepsin B is implicated in the pathology of chronic inflammatory diseases
      of airways and joints, and in cancer and pancreatitis. In this short review we
      outline the major structural features of the enzyme, and describe how these
      relate to its synthesis, trafficking, processing and function.

PMID- 9251239
TI  - The alpha v beta 3 integrin "vitronectin receptor".
AB  - The alpha v beta 3 "vitronectin receptor" is a member of the integrin superfamily
      of adhesion molecules. As such, this 160/85 kDa heterodimeric protein exhibits
      many of the typical structural and functional features of integrins. It mediates
      cell adhesion to extracellular matrix by recognizing the conserved arg-gly-asp
      (RGD) sequence of several plasma and matrix proteins. Recently, it has also been
      shown that alpha v beta 3 is involved in signal transduction and cell to cell
      interactions. alpha v beta 3 is highly expressed in bone resorbing cells,
      osteoclasts, and upregulated in response to vascular damage, during angiogenesis
      and in certain types of malignancy. Antagonists of alpha v beta 3 are being
      developed for use in a variety of diseases associated with altered receptor
      function or level.

PMID- 9251240
TI  - Kinase-related protein: a smooth muscle myosin-binding protein.
AB  - Kinase-related protein (telokin) is a small myosin-binding protein which has
      recently been discovered in smooth muscle. The KRP messenger RNA is transcribed
      from within the myosin light chain kinase (MLCK) gene, a rare example in
      vertebrates of two proteins coded for by a single gene. Owing to a separate
      transcription unit and a common reading frame, kinase-related protein is
      expressed as an independent protein which consists of the C-terminal 156 amino
      acids of the kinase. It binds specifically to dephosphorylated smooth muscle
      myosin and inhibits myosin phosphorylation by MLCK in vitro, suggesting that it
      might modify the rate of myosin activation and consequently the rate of tension
      development in the muscle. KRP also stabilizes an extended conformation of
      dephosphorylated myosin which can polymerize, and thereby stabilizes myosin in
      the filamentous state against the dissociating effect of ATP. Thus, kinase
      related protein may have a function in regulating the assembly of myosin
      filaments into the contractile apparatus in the cell.

PMID- 9251241
TI  - The role of chromatin in transcriptional regulation.
AB  - Transcriptional activation is mediated by the facilitated binding of the basal
      transcription complex to the transcription start site of a promoter. The
      activation procedure involves protein-protein interactions between specific
      transcription factors and members of the basal transcription complex. However,
      since eukaryotic DNA is packaged with histones into nucleosomes the accessibility
      of the transcription factors is limited. In order to activate transcription, some
      of the specific transcription factors must have the capacity to bind to their
      binding sites when organized into nucleosomes. As a next step, the chromatin
      structure of the promoter needs to be decondensed in order to facilitate the
      binding of the basal transcription machinery. Recent data have addressed these
      issues and both binding of transcription factors to their chromatin binding site
      as well as transcription factor-induced chromatin remodelling have been
      demonstrated. In addition, factors that are candidates to mediate the chromatin
      remodelling have recently been identified and characterized. The ability of a
      transcription factor to recognize its cognate element in a nucleosome is an
      inheret property that differs among different transcription factors. The
      implications of the rotational and translational positioning of the DNA within a
      nucleosome on the accessibility of a transcription factor is described in this
      review. In addition, nucleosome rearrangement and juxtaposing in the context of
      transcriptional activation is also discussed.

PMID- 9251242
TI  - Biological methylation of myelin basic protein: enzymology and biological
      significance.
AB  - Myelin is a membrane characteristic of the nervous tissue and functions as an
      insulator to increase the velocity of the stimuli being transmitted between a
      nerve cell body and its target. Myelin isolated from human and bovine nervous
      tissue is composed of approximately 80% lipid and 20% protein, and 30% of the
      protein fraction constitutes myelin basic protein (MBP). MBP has an unusual amino
      acid at Res-107 as a mixture of NG-monomethylarginine and NG, N'G
      dimethylarginine. The formation of these methylarginine derivatives is catalysed
      by one of the subtypes of protein methylase I, which specifically methylates Res
      107 of this protein. Evidence is presented to demonstrate an involvement of this
      biological methylation in the integrity and maintenance of myelin.

PMID- 9251243
TI  - The gene for the human interleukin-11 receptor alpha chain locus is highly
      homologous to the murine gene and contains alternatively spliced first exons.
AB  - The gene for the murine interleukin-11 receptor alpha chain (mIL-11R alpha)
      contains two loci (1 and 2), of which locus 2 is restricted to only some mouse
      strains. Two alternatively spliced exons (1a and 1b) encode the 5' untranslated
      region (5'UTR) of the murine locus 1. We have characterized the gene for the
      human interleukin-11 receptor alpha chain locus (hIL-11R alpha), examined its
      expression by Northern analysis and determined its chromosomal location by
      fluorescence in situ hybridization. The presence of exon(s) encoding the 5'UTR
      and mapping of transcription initiation sites was determined by reverse
      transcriptase polymerase chain reaction and 5' rapid amplification of cDNA ends
      (5'RACE) techniques. The human locus spanned 10 kilobasepairs (kb) and consisted
      of 14 exons. Two alternatively spliced first exons (1a and 1b) encoding the 5'UTR
      were identified and shared 76 and 73% nucleotide identity with murine exons 1a
      and 1b. Multiple transcription start sites were demonstrated for human exon 1a.
      The promoter regions of both human exons 1a and 1b did not display a canonical
      TATA box. A predominant 1.8 kb transcript for the hIL-11R alpha was present in
      heart, brain, skeletal muscle, lymph nodes, thymus, appendix, pancreas and foetal
      liver. The hIL-11R alpha gene was localized to chromosome 9p13. In summary, the
      hIL-11R alpha gene was highly related to locus 1 of the murine gene and there was
      no evidence of a second hIL-11R alpha locus.

PMID- 9251244
TI  - Synthesis of a new phosphoglycolipid with biological activity towards platelets.
AB  - Various synthetic as well as naturally occurring compounds have been found to
      exhibit platelet-activating factor (PAF)-like activity or to act as specific PAF
      inhibitors. In this work we have synthesized a new phosphoglycolipid, methyl
      2,3,4-tri-O-acetyl-6-(1'-O-stearoyl-2'-O- acetyl-DL-glycero-3'-phosphoryl)-alpha
      D-glucopyranoside ammonium salt, using a combination of known synthetic steps.
      This phosphoglycolipid was first purified on TLC (Rf 0.7, using
      chloroform/methanol/water, 65:25:4, v/v/v as solvent system). It was further
      purified onto a high performance liquid chromatography silica column with an
      elution system that contained acetonitrile and methanol (retention time 13.5
      min). Its identification was based on chemical determinations and electrospray
      mass spectrometry analysis. The above compound induced washed platelet
      aggregation with an EC50 value at 2 x 10(-4) M. The aggregation curve was
      biphasic, the first wave of which was through the PAF way while the second one
      was through the ADP way. Treatment with acetylhydrolase resulted in a rapid
      decrease of the first wave of aggregation and in a slow decrease of the second
      wave. In lower concentrations, the phosphoglycolipid inhibited PAF- and thrombin
      induced aggregation with IC50 values of the order of 10(-7) M. In conclusion,
      this phosphoglycolipid has a diverse biological activity. The PAF-like activity
      of this new lipid enforces the conception that PAF is a member of a large family
      consisting of lipid mediators.

PMID- 9251245
TI  - Oxidative stress mediates monocrotaline-induced alterations in tenascin
      expression in pulmonary artery endothelial cells.
AB  - Oxidative stress may be involved in monocrotaline (MCT)-induced endothelial cell
      injury and upregulation of extracellular matrix proteins in the pulmonary
      vasculature. To test this hypothesis, cytotoxicity, expression and distribution
      of tenascin (TN) as well as cellular oxidation were determined in porcine
      pulmonary artery endothelial cells (PAECs) exposed to MCT and/or to an oxygen
      radical scavenger, dimethylthiourea (DMTU). Relative to controls, treatment with
      2.5 mM MCT for 24 hr produced cytotoxicity as evidenced by changes in cellular
      morphology, cell detachment, hypertrophy, reduction in cellular proliferation and
      severe cytoplasmic vacuolization. Parallel studies showed that MCT markedly
      altered the expression and distribution of TN in PAEC as determined by
      immunocytochemistry. Western analysis showed that MCT increased cellular TN
      content and promoted the appearance of an additional, smaller TN isoform.
      Northern analysis demonstrated an increase in the steady-state level of TN
      specific mRNA in response to MCT treatment. Exposure to MCT also increased the
      synthesis of cell-associated and media-associated TN as determined by
      immunoprecipitation. In addition, MCT increased the intensity of cellular
      oxidative stress as measured by 2,7-dichlorofluorescein fluorescence. Co
      treatment with DMTU prevented MCT-induced cytotoxicity, alterations in TN
      distribution and content, and reduced the increase in DCF fluorescence. These
      results suggest that MCT-induced cytotoxicity and upregulation of TN are
      mediated, at least in part, by induction of cellular oxidative stress.

PMID- 9251246
TI  - Purification of M5, a fibrinolytic proteinase from Crotalus molossus molossus
      venom that attacks complement.
AB  - Crotalus molossus molossus (northern blacktailed rattlesnake) venom contains
      agents that affect blood coagulation. A fibrin(ogen)olytic proteinase, called M5,
      was isolated and purified from this venom by ion exchange chromatography in a two
      step procedure. M5 consists of a single non-glycosylated polypeptide chain with a
      molecular weight of 25 kDa and an isoelectric point of 7.6. It hydrolyses the A
      alpha and B beta chains of fibrinogen and the alpha and beta chains of fibrin. It
      also exhibits caseinolytic activity, but has no effect on synthetic substrates
      cleaved by thrombin, plasmin, kallikrein, or trypsin. The proteolytic activity of
      the enzyme against fibrinogen, fibrin, and casein is inhibited by
      ethylenediaminetetraacetic acid (EDTA) and the loss of activity by EDTA treatment
      can be prevented by addition of Zn2+. This suggests that M5 is a zinc
      metalloproteinase. M5, at doses of 50 micrograms and higher, induces significant
      hemorrhage when injected subcutaneously into mice. In addition, it inactivates
      guinea-pig complement in a dose-dependent fashion and hydrolyses human C2, C3,
      and C4.

PMID- 9251247
TI  - Tissue-specific and developmental stage-dependent expression of a novel rat
      Dopa/tyrosine sulfotransferase.
AB  - Tissue-specific and developmental stage-dependent expression of a novel
      Dopa/tyrosine sulfotransferase in Sprague-Dawley rats was examined. Both
      immunoblot and Northern blot analyses showed that the enzyme was expressed
      predominantly in liver and to a lesser extent in kidney. Its expression could not
      be detected in nine other organs tested. Livers from different age groups of male
      or female rats were examined for the developmental regulation of the expression
      of the Dopa/tyrosine sulfotransferase. Results from immunoblot and Northern blot
      analyses revealed that the enzyme was present at a very low level in livers of 1
      day-old to 2-week-old rats, and gradually increased to a maximum level in rats
      older than 2 months. Data from the enzymatic assays also showed a similar trend
      of expression in both male and female rats. The Dopa/tyrosine sulfotransferase
      activities detected in liver samples of the 8-week-old male and female rats were,
      respectively, 8.6 and 6.6 times that of the activities detected in liver samples
      of the 1-day-old male and female rats. These data provide a foundation for the
      future investigation of the cis- and trans-acting factors involved in the
      regulation of the tissue-specific and developmental stage-dependent expression of
      this enzyme.

PMID- 9251248
TI  - Rat GST 8-8 is expressed predominantly in myeloid origin cells infiltrating the
      gravid uterus.
AB  - Previous studies from our laboratory have shown a relatively high expression of
      rGST8-8 in uterine tissues. This GST isozyme displays relatively high glutathione
      peroxidase activity towards lipid-hydroperoxides and towards toxic 4
      hydroxyalkenals generated from lipid peroxidation. Since the uterus is a unique
      organ, subject to oxidative stress due to infiltration by immune effector cells
      during gestation and because this infiltration is readily identifiable
      histologically, the studies reported herein were performed to localize the cell
      specific expression of rGST8-8 to determine whether immune effector cells
      infiltrating the pregnant rat uterus specifically expressed rGST8-8. A 75 bp end
      radiolabeled cRNA probe was prepared from the full length mGSTA4-4 cDNA from the
      region which is highly homologous with rGST8-8. This cRNA probe was used for in
      situ hybridization studies to localize rGST8-8 in specific cell types of gravid
      rat uterus. Results of these studies indicate that this GST isozyme is
      selectively expressed in myeloid origin cells such as monocytes/macrophages, and
      neutrophils infiltrating the uterine endometrium and in vascular walls. Selective
      expression of rGST8-8 in the myeloid origin cells, which are known to generate
      higher levels of reactive oxygen species, suggests that this GST isozyme plays an
      important role in the protection mechanisms against lipid peroxidation.

PMID- 9251249
TI  - Effect of sphingomyelin and its metabolites on the activity of human recombinant
      PLC delta 1.
AB  - In an attempt to obtain sufficient quantities of pure phospholipase C delta 1
      (PLC delta 1) necessary for structural and kinetic studies, human fibroblast PLC
      delta 1 was cloned in the pPROEX-1 vector, expressed in E. coli cells as a
      (6xHis) fusion protein and purified to homogeneity. From 11 of E. coli culture 21
      mg of pure PLC delta 1 was obtained by a two-step purification procedure, which
      includes Ni(2+)-NAT agarose and Mono S cation exchange chromatography. Catalytic
      properties of recombinant PLC delta 1 with respect to activation by spermine and
      calcium ions and inhibition by sphingomyelin were similar to or identical to PLC
      delta 1 purified from rat liver. Calcium activation of PLC delta 1 was dependent
      on the presence of spermine. Half-maximal activity was attained at 250 and 170 nM
      of free Ca2+ in the presence and absence of spermine, respectively. Sphingomyelin
      and lysosphingomyelin were mixed type inhibitors with respect to PIP2. Ceramide
      inhibits PLC delta 1 very weakly. GM1, which is a ceramide bound glucosidically
      to the oligosaccharide moiety, was a strong non-competitive inhibitor of PLC
      delta 1. In the absence of spermine, sphingosine and phytosphingosine weakly
      activated PLC delta 1. The results indicate that the effect of sphingomyelin and
      its metabolites on PLC delta 1 activity depends on the presence of spermine. It
      is postulated that, among other factors, in vivo, activity of PLC delta 1 may
      depend on the turnover of sphingomyelin.

PMID- 9251250
TI  - Isolation and characterization of a leukemia inhibitory factor-independent
      embryonic stem cell line.
AB  - Leukemia inhibitory factor (LIF) is a mammalian cytokine that has a wide range of
      physiological activities, including the inhibition of differentiation of
      embryonic stem (ES) cells. We have used insertional mutagenesis in an attempt to
      isolate molecules that participate in LIF signal transduction via the LIF
      receptor. Using a robust screen for undifferentiated cells, we have isolated one
      ES cell line, Poly 27, that does not require exogenous LIF to remain
      undifferentiated in vitro. We present evidence that Poly 27 is not irreversibly
      committed to an undifferentiated phenotype, but can differentiate in vitro if
      cultured in the presence of chemical differentiating agents, while in syngeneic
      mice Poly 27 cells form tumours which are composed largely of undifferentiated
      cells. We have characterized the mechanism of factor independence in Poly 27, and
      shown it to be a result of autocrine LIF production. This LIF production is
      potentially the result of a mutation in a gene critically involved in regulating
      LIF production in ES cells.

PMID- 9251251
TI  - Generation of chromophore Tyr-containing mutants of the ribosomal protein L7/L12
      from Escherichia coli by site-directed mutagenesis and characterization.
AB  - The ribosomal protein L7/L12 from Escherichia coli has two domains with different
      structure-a globular C-terminal domain and a non-globular elongated N-terminal
      domain. The N-terminal domain of the protein has been subjected to site-directed
      mutagenesis to introduce the chromophore Tyr and to study its structure by
      spectroscopic methods. The mutant proteins S1Y, M14Y and M26Y were expressed at
      high levels in Escherichia coli and purified to homogeneity by ion-exchange
      chromatography and gel-filtration. Growth and purification protocols were
      optimized to allow reproducible and efficient production of mutant proteins. The
      effects of the replacements were assessed by UV, far-UV circular dichroism (CD),
      DSC and 1H-NMR studies. The spectroscopic characteristics (far-UV CD and 1H-NMR)
      and the thermal unfolding (far-UV CD and DSC) of the mutants have shown that
      these single mutations in the N-terminal region of the protein have no
      appreciable effect on its secondary and tertiary structures. 1H-NMR spectroscopy
      was used to show that the Tyr mutants retain their dimer structure. The
      initiating Met is the first amino acid in the mutant protein S1Y. Y2(S1) is
      located in a structurally disordered region of the N-terminal domain of the
      protein S1Y and does not seem to have close amino acid neighbours. Y14(M14) and
      Y26(M26) participate in the structurally ordered regions of the molecule. Phe30
      is situated in the surroundings of Y14. The unchanged structure resulting from
      the mutations makes these proteins highly suitable for structural studies by
      multidimentional NMR to determine the structure of the N-terminal domain of
      protein L7/L12.

PMID- 9251252
TI  - Analogous activation of bovine liver glycogen phosphorylase by AMP and IMP.
AB  - The mechanism of activation of glycogen phosphorylase is incompletely understood,
      although adenosine and inosine nucleotides are known to be important allosteric
      activators. In this study the activation of glycogen phosphorylases a and b from
      bovine liver by adenosine 5'-monophosphate (AMP) and inosine 5'-monophosphate
      (IMP) has been investigated and the results compared with the activation of the
      muscle isozyme by the same nucleotides. Enzyme activity was determined by
      spectrophotometric measurement of inorganic phosphate produced in the
      phosphorylase-catalysed reaction of glycogen synthesis. Liver phosphorylase b
      binds both nucleotides non-co-operatively (Hill coefficients of 1.0 +/- 0.1),
      with changes in the maximum velocity to 75 or 80 mumol min-1 mg-1 in the presence
      of adenosine 5'-monophosphate or inosine 5'-monophosphate, respectively, but no
      change in the enzyme affinity towards the substrate, glucose-1-phosphate. Binding
      of glucose-1-phosphate is co-operative and the kinetic data have been fitted with
      the Monod-Wyman-Changeux model. Liver phosphorylase a has a maximum velocity
      similar to that of the b form in the presence of nucleotides. Binding of glucose
      1-phosphate to the enzyme is non-co-operative (Hill coefficient of 1.0 +/- 0.1)
      and the affinities in the presence of the nucleotides (Michaelis constants of 28
      +/- 0.2 mM or 27 +/- 0.2 mM for adenosine 5'-monophosphate or inosine 5'
      monophosphate) are stronger than those of the b form. It is concluded that the
      activity of bovine liver phosphorylase a and b is similarly influenced by
      adenosine 5'-monophosphate or inosine 5'-monophosphate. The b form seems to
      behave like muscle phosphorylase b in response to inosine 5'-phosphate; however,
      the binding of adenosine 5'-phosphate does not induce the conformational change
      necessary to activate the liver enzyme, as occurs with the muscle isozyme.

PMID- 9251253
TI  - The photoreceptors and visual pigments of the garter snake (Thamnophis sirtalis):
      a microspectrophotometric, scanning electron microscopic and immunocytochemical
      study.
AB  - Scanning electron microscopy, immunocytochemistry, and single cell
      microspectrophotometry were employed to characterize the photoreceptors and
      visual pigments in the retina of the garter snake, Thamnophis sirtalis. The
      photoreceptor population was found to be comprised entirely of cones, of which
      four distinct types were identified. About 45.5% of the photoreceptors are double
      cones consisting of a large principal member joined near the outer segment with a
      much smaller accessory member. About 40% of the photoreceptors are large single
      cones, and about 14.5% are small single cones forming two subtypes. The outer
      segments of the large single cones and both the principal and accessory members
      of the doubles contain the same visual pigment, one with peak absorbance near 554
      nm. The small single cones contain either a visual pigment with peak absorbance
      near 482 nm or one with peak absorbance near 360 nm. Two classes of small single
      cones could be distinguished also by immunocytochemistry and scanning electron
      microscopy. The small single cones with the 360-nm pigment provide the garter
      snake with selective sensitivity to light in the near ultraviolet region of the
      spectrum. This ultraviolet sensitivity might be important in localization of
      pheromone trails.

PMID- 9251254
TI  - Ontogeny of the electric organ discharge and the electric organ in the weakly
      electric pulse fish Brachyhypopomus pinnicaudatus (Hypopomidae, Gymnotiformes).
AB  - I recorded the electric organ discharges (EODs) of 331 immature Brachyhypopomus
      pinnicaudatus 6-88 mm long. Larvae produced head-positive pulses 1.3 ms long at 7
      mm (6 days) and added a second, small head-negative phase at 12 mm. Both phases
      shortened duration and increased amplitude during growth. Relative to the whole
      EOD, the negative phase increased duration until 22 mm and amplitude until 37 mm.
      Fish above 37 mm produced a "symmetric" EOD like that of adult females. I stained
      cleared fish with Sudan black, or fluorescently labeled serial sections with anti
      desmin (electric organ) or anti-myosin (muscle). From day 6 onward, a single
      electric organ was found at the ventral margin of the hypaxial muscle.
      Electrocytes were initially cylindrical, overlapping, and stalk-less, but later
      shortened along the rostrocaudal axis, separated into rows, and formed caudal
      stalks. This differentiation started in the posterior electric organ in 12-mm
      fish and was complete in the anterior region of fish with "symmetric" EODs. The
      lack of a distinct "larval" electric organ in this pulse-type species weakens the
      hypothesis that all gymnotiforms develop both a temporary (larval) and a
      permanent (adult) electric organ.

PMID- 9251255
TI  - The effects of nerve growth factor and anti-nerve growth factor antibody on the
      neuroendocrine reproductive system in the European starling Sturnus vulgaris.
AB  - Thyroidectomy of starlings causes them to remain in breeding condition
      indefinitely; deactivation of gonadotrophin-releasing hormone neurons that is
      characteristic of photorefractoriness does not occur. We hypothesise that a
      neurotrophin, whose presence or ability to function is dependent upon thyroid
      hormones, is somehow involved in this termination of gonadotrophin-releasing
      hormone release. Nerve growth factor is one such candidate. Mouse 7S-nerve growth
      factor dissolved in artificial cerebro-spinal fluid was therefore infused into
      the lateral ventricle of thyroidectomised male starlings held on long days four
      times daily for 21 days and 31 days, in separate experiments, to see if
      photorefractoriness would occur. The result was significant gonadal regression in
      the treatment groups during the infusion period, with no change in testicular
      volume in the control groups. Testicular recrudescence occurred after the end of
      the treatment period. To see if this was a non-specific effect, or progression
      towards photorefractoriness per se, we used castrated, photorefractory starlings
      held on long days. Anti-nerve growth factor antibody was infused into the lateral
      ventricle at increasing concentrations and frequency. There was a significant
      rise in circulating luteinising hormone levels in the treatment groups as
      compared to controls, increasing with antibody dosage.

PMID- 9251256
TI  - Characterization of respiratory-related neurons in the isolated brainstem of the
      frog.
AB  - Using intra- and extracellular recording techniques we examined the spontaneous
      discharge and membrane properties of respiratory-related neurons in isolated
      brainstem preparations of the frogs Rana catesbeiana and Rana pipiens that
      display spontaneous respiratory related activity in vitro. We observed neurons
      that depolarize during the fictive lung ventilation cycle as well as neurons that
      depolarize during the non-lung ventilation phase. Respiratory-related neurons
      demonstrated significant decreases in membrane input resistance during the
      fictive lung ventilation cycle but showed no evidence of voltage-dependent
      membrane conductances activated near resting membrane potential. Furthermore,
      respiratory neurons showed little spike frequency adaptation, their oscillatory
      activity was not dissociated from the global respiratory motor output following
      imposed changes in membrane potential, and spontaneous fluctuations in membrane
      potential were not observed following reversible interruption of respiratory
      burst activity by application of solutions low in calcium and high in magnesium.
      Taken together these results suggest that bulbar respiratory neurons in the
      isolated frog brainstem sampled in our study do not display endogenous bursting
      characteristics. Rather, they are strongly influenced by synaptic input.

PMID- 9251257
TI  - Neural correlates of behavioral gap detection in the inferior colliculus of the
      young CBA mouse.
AB  - The gap detection paradigm is frequently used in psychoacoustics to characterize
      the temporal acuity of the auditory system. Neural responses to silent gaps
      embedded in white-noise carriers, were obtained from mouse inferior colliculus
      (IC) neurons and the results compared to behavioral estimates of gap detection.
      Neural correlates of gap detection were obtained from 78 single neurons located
      in the central nucleus of the IC. Minimal gap thresholds (MGTs) were computed
      from single-unit gap functions and were found to be comparable, 1-2 ms, to the
      behavioral gap threshold (2 ms). There was no difference in MGTs for units in
      which both carrier intensities were collected. Single unit responses were
      classified based on temporal discharge patterns to steady-state noise bursts.
      Onset and primary-like units had the shortest mean MGTs (2.0 ms), followed by
      sustained units (4.0 ms) and phasic-off units (4.2 ms). The longest MGTs were
      obtained for inhibitory neurons (x = 14 ms). Finally, the time-course of
      behavioral and neurophysiological gap functions were found to be in good
      agreement. The results of the present study indicate the neural code necessary
      for behavioral gap detection is present in the temporal discharge patterns of the
      majority of IC neurons.

PMID- 9251259
TI  - Study of suspected plague cases for isolation and identification of Yersinia
      pestis.
AB  - A total of 62 suspected patients of plague were investigated for evidence of
      Yersinia pestis, by blood culture, lymph node aspirate culture, sputum culture,
      animal inoculation and serology for f1 antibodies against f1 antigen of Yersinia
      pestis. None of the samples was positive by direct smear examination and culture
      for Yersinia pestis, as well as for serology. The non positivity of the cultures
      is discussed.

PMID- 9251258
TI  - Synaptic transmission in the pineal eye of young Xenopus laevis tadpoles: a role
      for NMDA and non-NMDA glutamate and non-glutaminergic receptors?
AB  - The pineal eye of Xenopus laevis tadpoles is directly photosensitive. A sudden
      reduction in light intensity produces a burst of activity in the pineal ganglion
      cells, which is closely followed by the onset of swimming. In this paper I
      present the results of experiments on the effects of agonists and antagonists of
      candidate pineal transmitters on ganglion cell activity. I found that NMDA and
      non-NMDA excitatory amino acid (EAA) agonists increased pineal activity,
      indicating the presence of both types of receptor. Kynurenic acid reduced
      activity, thus confirming that the photoreceptor transmitter is an EAA. Under
      physiological conditions, CNQX blocked activity almost completely whilst AP5 had
      little effect. In Mg(2+)-free saline CNQX had a considerably smaller effect, but
      joint application of CNQX and AP5 blocked almost all activity; therefore, the
      NMDA receptors are subject to blockage by Mg2+. Although GABAA and ACh receptors
      appear to be present, no evidence was found for GABA or ACh as pineal
      transmitters. In addition, 5-HT had no effect on pineal activity. The main pineal
      transmitter is an EAA acting on ganglion cells through both NMDA and non-NMDA
      receptors. Other receptors are present but appear to have no role in controlling
      pineal activity at this stage.

PMID- 9251260
TI  - Neural hyperplasia in appendix.
AB  - One hundred fifty histologically non-inflamed appendices from patients with acute
      appendicular pain were studied for mucosal and submucosal neurogenous hyperplasia
      using simple histochemical stain. Mucosal and submucosal neural hyperplasia was
      found in 69.34% of cases. The severity of submucosal hyperplasia was more
      compared to mucosal. The neural hyperplasia of higher grade was found mainly in
      the age group between 21 to 40 years. The appendicular pain in three unwarranted
      surgical cases may be either due to neural hyperplasia or substances liberated
      from closely associated neuroendocrine/mast cells.

PMID- 9251261
TI  - Kleine-Levin syndrome--a case report with a brief review.

PMID- 9251262
TI  - Information systems and ophthalmology.

PMID- 9251263
TI  - Fluid vitreous substitutes in vitreo retinal surgery.
AB  - Advances in the surgical instrumentation and vitreoretinal techniques have
      allowed intraoperative reapproximation of retina to a more normal position. The
      use of intravitreally injected liquid materials (viscoelastic liquids, liquid
      perfluorocarbons and silicone oil), as adjunctive agents to vitreo-retinal
      surgery play an important role in facilitating retinal reattachment. These
      materials are used as intraoperative instruments to re-establish intraocular
      volume, assist in separating membranes adherent to the retina, manipulate retinal
      detachments and mechanically flatten detached retina. Over the longer term,
      silicone oil maintains intraocular tamponade. One should be cognizant of the
      potential uses, benefits and risks of each of these vitreous substitutes.

PMID- 9251264
TI  - Methods for estimating prevalence and incidence of senile cataract blindness in a
      district.
AB  - The problem of senile cataract blindness (SCB) is very acute in India,
      contributing to 80 per cent of total blindness. The national objective of
      reducing the prevalence of blindness from 1.49 per cent, during 1986-89 to 0.3
      per cent by AD 2000 has necessitated the surgical correction of SCB to be the
      major activity. With the introduction of District Blindness Control Society
      (DBCS), there has been a substantial increase in the number of operations of SCB
      in those districts. However, in the absence of standard, feasible, simple and
      cost effective methods to estimate the prevalence and incidence of SCB, the DBCS
      may find it difficult to plan and execute its major activity in a realistic way.
      The paper suggests two such methods for the use by DBCS. Only five seemingly
      rational assumptions have been adopted for the purpose. The authors feel that
      proper field testing is required to be sure about the reliability and validity of
      these methods.

PMID- 9251265
TI  - A case control study of senile cataract in a hospital based population.
AB  - A case-control study (244 cases and 264 controls) was done during 1986-89 on a
      hospital based population to evaluate the risk factors associated with the
      etiology of senile cataract. Patient with age between 40-60 years, visual acuity
      of 6/9 or less, and presence of lenticular opacity of senile origin were included
      as cases. Age matched individuals with absence of lenticular opacity made up the
      controls. Multivariate logistic regression analysis revealed that higher systolic
      BP and number of meals were significantly (P < or = 0.05) associated with
      presence of senile cataract; whereas higher weight, education and income, and
      utilization of cooking water had a significant protective effect against senile
      cataract. The present study helps the clinician to understand the possible risk
      factors associated with the development of senile cataract and could be helpful
      in designing a intervention strategy in future.

PMID- 9251266
TI  - Graded corneal sensitivity for screening of diabetic retinopathy.
AB  - Several alternative approaches to screen diabetics followed by referral of
      patients with retinopathy changes, are being investigated. The intent is to
      demonstrate usefulness of a cost effective, easy and valid screening test. We
      investigated in this report the efficacy of graded corneal sensitivity for
      screening presence of diabetic retinopathy. In 105 randomly chosen subjects with
      (70 subjects) and without (35 subjects) diabetes mellitus, corneal aesthesiometry
      and status of retinopathy was determined independently. Corneal sensitivity in
      subjects of diabetes mellitus without retinopathy (1.17 +/- 0.29 gm/mm2) was
      significantly different when compared to healthy controls (0.99 +/- 0.04 gm/mm2)
      (p < 0.01). Also corneal sensitivity in eyes with any type of retinopathy was
      significantly worse (1.94 +/- 1.33 gm/mm2) when compared to eyes without
      retinopathy. At a cut off value of 1.20 gm/mm2 the sensitivity and specificity of
      corneal hypoesthesia as a test to detect diabetic retinopathy was 86% and 74%,
      respectively. For detecting presence of proliferative diabetic retinopathy at a
      cut off value of 1.49 gm/mm2 the sensitivity and specificity were 89% and 80%
      respectively. These observations indicate that corneal hypoesthesia may be a
      reasonable indication of the presence of diabetic retinopathy and could be used
      to screen diabetic populations for retinopathy, after its validity is confirmed
      in larger studies.

PMID- 9251268
TI  - Orbital myocysticercosis presenting as subconjunctival abscess.

PMID- 9251267
TI  - Pre-septal cellulitis--varied clinical presentations.
AB  - Preseptal cellulitis has a typically benign course when treated with antibiotics,
      the clinical course depending on age of the patient, aetiology and the causative
      organism. In this study, 14 cases of preseptal cellulitis are documented with the
      age ranging from 2 to 55 years. The organisms isolated were Staphylococcus aureus
      (7 cases), Streptococcus pyogenes (2 cases) and Pseudomonas aeruginosa (1 case).
      In the remaining four patients no organism could be identified. All except four
      patients were cured within 6 weeks. Complications seen included lagophthalmos,
      lid abscess, cicatricial ectropion and lid necrosis in one patient each. The
      prognosis for preseptal cellulitis is good with appropriate antibiotics and
      surgical therapy.

PMID- 9251270
TI  - A new model eye system for practicing indirect ophthalmoscopy.

PMID- 9251269
TI  - Mucoepidermoid carcinoma of the conjunctiva of the lower lid--report of a case.

PMID- 9251271
TI  - Optic disc evaluation in glaucoma.

PMID- 9251272
TI  - Cataract blindness on the rise? Results of a door-to-door examination in Mohadi.
AB  - A census survey in Mohadi block, Bhandara district of Maharashtra, indicated that
      the prevalence of blindness and cataract blindness has increased, compared with
      the 1986 survey. Around one third of the persons blind from cataract have been
      covered by surgical services. To increase coverage, more emphasis on information,
      education and communication is essential.

PMID- 9251273
TI  - The fetal origins of coronary heart disease and non-insulin dependent diabetes in
      India.

PMID- 9251274
TI  - Haemophilus influenzae type b vaccine in India: need and timing, immunogenecity
      and tolerance.
AB  - OBJECTIVE: (i) To assess the natural immunity and susceptibility to Haemophilus
      influenzae type b (Hib) infections in children in India. (ii) To study the
      immunogenecity and tolerance of Hib vaccine (ACTHIB) in young infants. DESIGNS:
      (i) Cross sectional study. (ii) Prospective trial. SETTING: Well baby and
      immunization clinics. METHODS: (i) PRP antibody titers against Hib estimated in
      172 healthy infants and children aged 1 month to 10 years. (ii) Antibody titres
      estimated before and after ACTHIB vaccine given with primary immunization (age
      group 6 to 8 weeks) in 50 babies. RESULTS: (i) Naturally protective levels of Hib
      antibodies found in less than 20% of infants under one year, but in over 80%
      above 4 years. (ii) Seroconversion after ACTHIB vaccination was 100% with very
      high protective levels. There were no significant adverse reactions. CONCLUSIONS:
      ACTHIB vaccine proved to be safe and highly immunogenic. As susceptibility to Hib
      is highest in the first year of life, the vaccine should be recommended in the
      primary immunization schedule (combined with DPT). The very high titers achieved
      suggest the possibility of decreasing the number of doses or the amount of
      antigen to reduce the prevalent high cost.

PMID- 9251275
TI  - Platelet aggregation and lipid profile in offsprings of young ischemics.
AB  - OBJECTIVE: To study the platelet aggregation and lipid profile in offsprings of
      young ischemic parents. DESIGN: Cross sectional. SETTING: Hospital based.
      METHODS: 40 adults under 45 years of age with proven CHD and their 50 offsprings
      comprised the study group. In the control group, 40 age matched adults with
      normal maximal treadmill test and their 50 off springs were included. All were
      screened for lipid profile and platelet aggregation. RESULTS: Platelet
      aggregation was significantly elevated in adults with CHD (44.0 +/- 15.5%)
      compared to controls (32.22 +/- 9.1%). Children of CHD adults also had
      significantly elevated aggregation (34.9 +/- 12.5%) compared to control
      offsprings (27.8 +/- 9.9%). Adult CHD subjects had significantly elevated serum
      cholesterol, LDL-cholesterol (LDL-C) and atherogenic index compared to control
      adults. The children in both groups had similar lipid profiles. CONCLUSION:
      Platelet aggregation is enhanced in offsprings of young ischemics. The potential
      of this index as a marker for early development of CHD needs to be explored.

PMID- 9251276
TI  - Exchange transfusion in septic neonates with sclerema: effect on immunoglobulin
      and complement levels.
AB  - OBJECTIVE: To study the effect of exchange transfusion (ET) on the levels of
      immunoglobulins (Ig) and C3 in neonatal sepsis with sclerema. DESIGN: Randomized
      controlled trial in a referral neonatal unit of a teaching hospital. SUBJECTS:
      Consecutive culture positive septic neonates with sclerema were enrolled and were
      randomized to undergo ET (study group, n = 20) or no ET (controls, n = 20).
      RESULTS: Mortality was 50% in the study group and 95% in controls. Gram negative
      organisms accounted for 85% in study group and 90% in controls. IgG, IgA and IgM
      levels rose significantly while C3 levels did not show significant rise 12-24
      hours after ET. Ig and C3 levels did not change significantly in the controls.
      CONCLUSION: ET with fresh whole blood in septicemic newborns with sclerema
      improves survival, particularly in the more premature group and significantly
      enhances, IgG, IgA and IgM levels.

PMID- 9251277
TI  - Approach to the management of a child with epilepsy.

PMID- 9251278
TI  - A paradigm shift--a new approach to the National Family Welfare Programme.

PMID- 9251279
TI  - Neonatal necrotizing enterocolitis.

PMID- 9251280
TI  - An outbreak of poliomyelitis in Jordan: clinical and epidemiologic observations.

PMID- 9251281
TI  - Hemiplegia.

PMID- 9251282
TI  - Autoimmune neonatal thrombocytopenia (AINT) successfully managed with intravenous
      immunoglobulins (IVIg).

PMID- 9251283
TI  - CMV mononucleosis complicated by meningoencephalitis in a normal host.

PMID- 9251284
TI  - Homocystinuria with early thromboembolic episodes and rapid response to high dose
      pyridoxine.

PMID- 9251285
TI  - Assessment of nutritional status of adolescents.

PMID- 9251286
TI  - Xerophthalmia prevalence in ICDS area in Tamil Nadu.

PMID- 9251287
TI  - Splenic infarct in falciparum malaria.

PMID- 9251288
TI  - Containment of measles outbreak by active immunization.

PMID- 9251289
TI  - Guillian-Barre syndrome: issues in etiology and management.

PMID- 9251290
TI  - Current status of newer antiepileptic drugs.

PMID- 9251291
TI  - Tinea capitis.

PMID- 9251292
TI  - Chemotherapy of malaria.

PMID- 9251293
TI  - Neurotensin pathway in the chicken thymus.

PMID- 9251294
TI  - Three cases of the musculocutaneous nerve not perforating the coracobrachialis
      muscle.
AB  - We encountered three anomalies in which the musculocutaneous nerve did not
      penetrate the coracobrachialis during a gross anatomy course in 1996. Two of the
      anomalies were present in the bilateral arms of the cadaver of an 89-year-old
      woman, and the other in the right arm of the cadaver of a 64-year-old man. In all
      of the anomlies the musculocutaneous nerve, the lateral cord of the brachial
      plexus, and the median nerve were contained in a common sheath of connective
      tissue. Thus, muscular branches to the flexor muscles of the upper arm and the
      lateral antebrachial cutaneous nerve seemed to arise from the cord and the median
      nerve. After the common sheath was removed, the musculocutaneous and median
      nerves were completely separated, or the fusion between the musculocutaneous and
      median nerves only remained partially. These variations are apparently not rare,
      and it is possible that the combined paralysis of the musculocutaneous and median
      nerves would occur. The present variation may be important to clinicians.

PMID- 9251295
TI  - Effects of folic acid deficiency in pregnant Wistar rats on the activities of D5
      3 beta hydroxysteroid dehydrogenase and glucose-6 phosphate dehydrogenase in the
      ovaries of their litters.
AB  - Histochemical studies of the activities of glucose-6-phosphate dehydrogenase (G-6
      PD) and D5-3 beta-hydroxysteroid dehydrogenase (D5-3 beta-HSD) in the ovaries of
      40 day old litters of Wistar rats whose mothers were folic acid deficient from
      the 13th day of gestation showed very weak or no enzyme activity. Biochemical
      estimations of these enzymes showed that the specific activity of 3 beta-HSD in
      the experimental animal was 20% that of control while that of G-6-PD in the
      experimental animals was 14% that of control. This implies that folic acid
      deficiency instituted at a critical period in gestation in Wistar rats adversely
      affects steroidogenesis in the ovaries of their litters.

PMID- 9251296
TI  - Fine structure of crest synapses in the locus coeruleus of the Japanese macaque
      (Macaca fuscata), with special reference to noradrenergic neurons.
AB  - The crest synapse and its related structures in the locus coeruleus (LC) of the
      Japanese monkey, Macaca fuscata, were electronmicroscopically studied using
      noradrenaline (NA) immunohistochemistry and tannic acid fixation. About 20% to
      25% of the noradrenergic input to the LC terminated at noradrenergic neurons.
      About 1/3 of these NA-NA connections formed crest synapses, although conversely,
      NA-immunoreactive (IR) terminals were found in 10% of all terminals forming crest
      synapses. The crests showing parent dendrites were clearly NA-IR, and definite
      nonNA-IR dendritic crests were not found. Thus, crest synapses were present
      almost exclusively on noradrenergic neurons in the monkey LC. The crests were
      composed of parallel postsynaptic membranes 120 to 130 nm in width and 550 to 610
      nm in length, accompanied by a thick-dense material of cytoplasm, and regular
      single rows of electron dense subjunctional bodies which were arranged in
      approximately 8 transverse rows. A maximum of 12 electron-dense subjunctional
      bodies per row were counted in the middle section, and decreased bilaterally in
      number. The crests further contacted with the dendritic spiny processes of
      neighboring NA-IR neurons. These results suggest that the crest synapse is an
      evolved and powerful synaptic structure which makes it possible for noradrenergic
      neurons in the LC to fire simultaneously at a slow and constant frequency
      depending on the behavioral state.

PMID- 9251297
TI  - [Expression of neurotrophin and IL-1 beta mRNAs following spinal cord injury and
      the effects of methylprednisolone treatment].
AB  - Glucocorticoid has been clinically used for the treatment of acute spinal cord
      injury (SCI) to enhance the neurological recovery, but the relevance of the use
      of steroid is not fully discussed. Neurotrophins play important roles in normal
      development of central and peripheral nervous system. It is reported that
      traumatic insults to the brain alter the expression of these neurotrophins. These
      responses are considered to trigger a cascade of cellular protection and repair.
      First, we investigated the temporal and spatial expression patterns of
      neurotrophin and IL-1 beta mRNAs in the area of spinal cord lesion. Second, we
      examined if methylprednisolone (MP) affects the expression of these genes in SCI.
      Male Sprague-Dawley rats (250-300 gms) were laminectomized at T10. Spinal cord
      was crushed by clipping (holding force 60 gms, 1 sec). Rats were killed at 1, 6,
      12, 24 h, and 72 h after the injury and the spinal cord was rapidly removed and
      frozen sections were cut. Second, the other group of rats were treated with MP
      (165 mg/kg) just after SCI and sacrificed at 6 h. The levels of neurotrophins and
      IL-1 beta mRNAs were evaluated by in situ hybridization histochemistry. IL-1 beta
      mRNA level was elevated at 1 h and 6 h and attenuated at 12 h. The increased
      level of BDNF and NT3 mRNAs were first observed at 6 h and the labeling was
      enhanced at 24 h and 72 h. In MP treated group, the levels of IL-1 beta, BDNF and
      NT3 mRNAs were attenuated compared with those of MP-untreated SCI group. Steroid
      hormone therapy diminishes the post-traumatic inflammatory cascades which produce
      edema and swelling and worsen neuronal injury. However, glucocorticoid may hinder
      the endogenous repair mechanism. Our data show that MP depress the production of
      BDNF and NT3 following SCI, which might be disadvantageous to the survival of
      spinal neurons.

PMID- 9251298
TI  - Forelimb muscle contraction induced by cerebral cortical stimulation after
      callosotomy: a myographic study in the mouse.
AB  - The effect of callosotomy upon motor control by the cerebral cortex on the
      forelimb was examined in the mouse. On the 10th day after callosotomy in the
      rostral or caudal part of the corpus callosum, the forelimb area of the cerebral
      motor cortex was stimulated intracortically with a microelectrode and muscle
      contraction of the forelimb was recorded by electromyography. Muscle contraction
      was observed in the contralateral forelimb in the mice of which callosal fibers
      were cut in the caudal part of the corpus callosum including the splenium
      corporis callosi as well as in the normal mice. On the other hand, muscle
      contraction was observed in the ipsilateral forelimb in the mice of which
      callosal fibers were incised in the rostral part of the corpus callosum including
      the genu, rostrum and trunk. The latency of the muscle contraction was about 0.5
      msec in the both groups of the callosotomized mice, as well as in the normal
      mice.

PMID- 9251299
TI  - [Job strain, social support and mental health: a study on the male heavy
      manufacturing workers].
AB  - OBJECT: The aim of this study is to explore the influence of work experience on
      workers' psychological function. Specifically, the researchers will examine the
      effect of job demand, decision latitude, job strain, and social support at
      worksite on the mental health status of male heavy manufacturing workers. METHOD:
      By purposive sampling, from October 1994 to March 1995, the present investigators
      implemented a self-administered questionnaire survey on the workers in southern
      Taiwan. The Karasek job strain model and its measure were embedded in the
      questionnaire to evaluate workers' perceptions of their job conditions. In
      addition, Chinese Health Questionnaire (CHQ) was utilized to evaluate the
      workers' status of mental health. RESULT: Totally, 1,117 workers were selected
      for this survey. An unviriate analysis showed the younger the workers, the lower
      their monthly income, and the newer their employment, were more likely to be
      classified as high risk in mental health status. The workers with more decision
      latitude and higher social support would be better in mental health status. In
      addition, it also showed that workers under high job strain were more likely to
      be in poor mental health status. Result from multivariate logistic regression
      showed those who served longer, had more decision automony, and had higher social
      support, were less likely to be in poor mental health status. Instead, those who
      sustained high job strain were more likely to be in poor mental health status.
      DISCUSSION: The implication from those findings for the implementation of health
      promotion program. would be raised, and the limitation of this inference would
      also be discussed.

PMID- 9251300
TI  - [A study on behavior towards injection among residents and physicians in
      Kaohsiung & Ping-tung area].
AB  - To understand why people in Taiwan preferred iatrogenic injection as their
      medical therapy, we surveyed the knowledge, attitude, and behavior of iatrogenic
      injection for people and doctors in Kaohsiung and Ping-tung area by
      questionnaire. The results of the survey are drawn below: 1. More than 91.7% of
      the interviewed people would like to receive iatrogenic injection as their
      medical therapy, and 78.1% of the parents would choose iatrogenic injection for
      their children. The reason majority were because doctors suggested that and the
      parents believed iatrogenic injection is a quicker way of recovery. 2. In this
      study, 72.1% of the people received injection as their usual mode of medical
      treatment, and 74.9% of them had received injection during the previous month.
      When they brought their children to the clinics, the percentages of the above two
      conditions were 60.4% and 59.7% respectively. The factors influencing the
      reception of injection for people were the efficacy of the injection, education
      level and medical insurance. The influencing factors for children were the
      parents' medical behavior and the parents' willingness to accept injection. 3.
      About 83% of the interviewed doctors preferred iatrogenic injection as treatment
      for their patients. Almost 60% of them agreed that more patients would receive
      injection after National Health Insurance. About 72% of the doctors would not
      change the treatment for their patients, no matter how the system of the medical
      insurance changes. They would choose the right treatment for the distinct
      disease.

PMID- 9251301
TI  - [Using self-efficacy in assessing self-care to the IDDM patients].
AB  - The purpose of this study was to test an Self-Efficacy Scale for IDDM patients to
      assess their self-care performances. Data were collected by convenience sampling
      method from 72 patients with IDDM at southern Taiwan from February 5 to June 15,
      1995. Two instruments were used in this study: the Insulin Management Diabetes
      Self-Efficacy Scale (IMDSES) and Diabetes Self-Care Scale. The following results
      were obtained. 1. Subjects had average levels of self-efficacy. The IMDSES Scale
      total mean was 70.59 (SD = 16.59). The highest and the lowest mean in all IMDSES
      subscales were blood sugar monitor (76.29, SD = 16.37) and the foot care (63.37,
      SD = 26.92) respectively. 2. Subjects had average levels of self-care. The
      Diabetes Self-Care Scale total mean was 68.80 (SD = 18.45). The highest and the
      lowest mean in all Diabetes subscale were insulin adjustment (75.01, SD = 20.22)
      and the foot care (61.07, SD = 27.70) 3. There was a strong correlation between
      the IMDSES Scale and the Diabetes Self-Care Scale (r = 0.94, p < 0.01). In
      addition, there were significant Pearson correlations between each of the all
      Diabetes Self-Efficacy subscales and their related Self-Care subscales (r = 0.93
      approximately 0.62, p < 0.01). These results supported the theoretical
      perspective of Bandura's self-efficacy. Individual with higher levels of self
      efficacy were better able to manage their diabetes self-care. Implications of
      these findings for nursing practice and research are discussed.

PMID- 9251302
TI  - [Correlates of couples' attitudes toward husband's childbirth participation].
AB  - The purpose of this study was to explore the couples' attitude toward husband's
      childbirth participation and its context. By a cross-sectional study, data were
      collected from 100 couples who plant to deliver at one medical center in southern
      Taiwan. The modified version of individual Traditionality-Modernity Scale, a
      Social Support Scale, Zung's Self-rating depression scale and Zung's Self-rating
      Anxiety Scale, and the Chinese Health Questionnaire were used. Findings indicated
      that 73.0% wives and 80.0% husbands showed a favorable attitude toward husband's
      childbirth participation. Four factors were identified to be associated with
      couples' favorable attitude: (1) wife's mental support; (2) welcome for newborn's
      coming; (3) share in the childbirth with the wife together; (4) curiosity about
      the labor. In contrast, four factors related to unfavorable attitude were found:
      (1) unhelpful for the wife; (2) folk taboo; (3) husband's psychological impact;
      and (4) wife's negative body image. Moreover, logistic multiple regression
      indicated that those wives who desired a boy or a girl and those husbands who had
      junior college or below education tended to anticipate husband's childbirth
      participation or tended to childbirth participation. In response to the social
      trend, it is necessary to conduct more childbirth classes and encourage husbands
      to be present in the delivery room in order to promote family-oriented care in
      our health care system.

PMID- 9251303
TI  - [Validation of the Chinese version of "the Drug Attitude Inventory"].
AB  - The purpose of this study was to evaluate the validity of the Chinese version of
      "the Drug Attitude Inventory" and determine whether it was an effective tool for
      clinical evaluation. In this study, we enlisted 183 patients, 94 male and 89
      female, with an average age of 34.6 years. They included outpatients,
      rehabilitation program patients as well as inpatients. Upon analysis of the
      collected data, three factors related well to the Chinese version of "the Drug
      Attitude Inventory", namely: subjective positive, dysphoric response, and
      subjective negative attitudes. In order to test the discriminant validity, we
      separated 53 patients into two groups, compliant and non-compliant, by appointed
      compliance relating to the outpatient clinic who were recent hospitalized
      inpatients and outpatients. These three factors correlated with each other well
      for most patients except for those with psychotic symptoms. These three factors
      demonstrated acceptable inter-item reliability (Kuder-Richardson formula 20),
      coefficient r and test-retest coefficient r. Construct validity was established
      and was capable of differentiating between compliant and non-compliant groups of
      patients. In short we have found the Chinese version of "the Drug Attitude
      Inventory" to be an effective, clinically evaluative tool. To test its predictive
      validity, however, further follow-up studies to determine whether these three
      factors discussed here can be used to predict drug compliance.

PMID- 9251304
TI  - [Coping behaviors of the elderly with positive physical examination results in
      Kaohsiung City].
AB  - The objectives of this study were as follows: first, to investigate the coping
      behaviors of the elderly facing the stress of disease after free physical
      examination; Second, to identify personal and disease characteristics, and the
      social support that influences coping behaviors in the elderly. The study sample
      consisted of 661 elderly patients who were found to have abnormal findings during
      a free physical examination provided by 11 regional health stations in Kaohsiung
      City. Data were collected with questionnaires through home interview. Four
      hundred and eighty-four subjects completed the questionnaires. Data were analyzed
      using SAS computer program. The major findings were as follows: 1.Problem
      oriented coping behaviors were the more frequently used. The most frequently used
      coping behaviors were "accepting the situation as it is", "reling on myself to
      solve problems", "hoping that things would get better", "seeking professional
      help", and "letting things follow their natural cause". 2. The relative variables
      for problem-oriented coping were marital status, religion, medical insurance,
      educational level, disease characteristics, and social support. Sex, marital
      status, religion, medical insurance, perceived disease severity, characteristics
      of health problem, and newly found abnormality at this free physical examination
      were the relative variables for affective-oriented coping. 3. The best predictive
      variables for using problem-oriented coping behaviors were medical insurance,
      self-esteem support from family and friends, tangible support from health
      professionals, emotional support from health professionals, and whether it was
      the first time the patients knew their health problems. Findings from this study
      had implications for development of nursing care plans for elderly clients, as
      well as for collaborative team exploration of coping behaviors in the elderly.

PMID- 9251305
TI  - [Multiple myeloma with oral manifestations--report of two cases].
AB  - Multiple myeloma is a neoplastic disorder of bone that originates from cells of
      bone marrow. It is most commonly seen within the age range of 50-80 years, cases
      under the age of 40 being rare. Men are affected more frequently than are women.
      Bone pain is the cardinal clinical symptom in multiple myeloma. Because of the
      destruction of bone, pathologic fracture is fairly common. In the oral
      manifestations, the mandible is involved far more frequently than the maxilla,
      especially the most active hematopoietic areas-the remus, angle and molar region
      of the mandible. Other signs and symptoms of jaw involvement include swelling,
      pain, and increased tooth mobility. Extraosseous lesions may result in
      paresthesia of soft tissue and gingival enlargement with bleeding tendency.
      Roentgenographic examination will usually reveal numerous punched-out lesions in
      a variety of bones. In addition, blood examination will reveal hyperglobulinemia
      and Bence-Jones protein may be present in the urine of myeloma patients. The
      histological features of myeloma are closely packed cells resembling plasma
      cells. Case 1 in this report is a 64-year-old female, who has been diagnosed as
      having multiple myeloma (IgG, lambda). She was referred to our hospital because
      of gingival swelling, bleeding and pain. Case 2 is a 60-year-old female suffering
      from spontaneous gingival bleeding. After blood, urine examination and bone
      marrow biopsy, multiple myeloma was diagnosed (IgG, lambda). This paper reports
      the clinical manifestations and treatment courses of these two cases, and the
      concerns of treatment of multiple myeloma are also discussed.

PMID- 9251306
TI  - [Ophthalmic manifestations of giant cell arteritis--two cases report].
AB  - Two elderly women had catastrophic visual loss due to giant cell arteritis. The
      other eyes of both were attacked within two weeks. Bilateral central retinal
      artery occlusion, negative temporal artery biopsy and relentless nature course
      were noted despite treatment with a high dose of corticosteroid in one case.
      Unilateral central retinal artery and ischemic optic neuropathy were noted in the
      other case with typical pictures in temporal artery biopsy.

PMID- 9251307
TI  - [Chemical burn caused by hydrofluoric acid in Kaohsiung area--a 5-year
      experience].
AB  - Hydrofluoric acid (HF) has been used extensively in industry and laboratory, and
      also is a common agent for occupational chemical burn. Severe pain and
      destruction of deep tissue layers occurred when skin was injured by hydrofluoric
      acid. Some fatal change may happen especially when hydrocalcemia was induced. For
      presentation of its special character and the use of antidote, we report one
      outbreak and six individual victims of hydrofluoric acid injury during the
      previous 5 years in Kaohsiung area. We hope medical personnel could have more
      accurate management and clinical care for those who are injured by HF, and
      workers should pay attention to any chemical agents they use to prevent any
      further injury as a result of careless use of such chemicals.

PMID- 9251308
TI  - Dum spiro, spero--while I breathe, I hope.

PMID- 9251309
TI  - Chaos--a new concept in science.

PMID- 9251310
TI  - Coronary angiographic findings in patients with diabetes: an exercise in
      cardiovascular epidemiology.
AB  - A study of 516 patients with diabetes mellitus who presented with chest pain and
      an equal number of matched controls without diabetes examined by selective
      coronary arteriography was undertaken. Detailed analysis of the angiograms showed
      that prevalence of CAD in diabetics with symptoms was 86.6%. This prevalence
      increased with age. Multivessel disease was more common in diabetics that in
      controls (p < 0.01). In diabetic patients disease involvement of proximal and
      distal segments in the same vessel was more common (p < 0.01). The Gensini score
      of quantitative expression of severity of CAD was higher in diabetics (p < 0.05).
      The number of occluded segments in the coronary tree was higher in diabetics (p <
      0.01). No correlation could be established between severity of disease and age,
      body mass index or duration of diabetes. It is concluded that diabetes affects
      the coronary arteries of Indian patients more adversely than those of non
      diabetics. The prevalence of CAD among diabetics increases linearly with age.

PMID- 9251311
TI  - Outcomes in the Guillain Barre syndrome: the role of steroids.
AB  - Guillain-Barre Syndrome (GBS) is one of the commonest demyelinating diseases of
      the peripheral nervous system. This retrospective cohort study reports the
      outcomes of 97 patients in a large teaching hospital in South India. Fifty
      patients were treated with steroids and 47 had no steroids. Twenty one of the 41
      evaluable patients in the steroid group had functional improvement at discharge
      as compared to 20 of 42 evaluable patients in the non-steroid group. Six patients
      in each group had worsening of their weakness. Steroids did not show any
      significant beneficial effect in either improving the disability scores at
      discharge (steroid-0.42 vs. non-steroid-0.29) or in reducing the duration of ICU
      stay (4 vs. 8 median days). A higher proportion of patients on steroids developed
      complications (p = 0.02). The median duration of hospital stay was 16 days in the
      steroid group as opposed to 14 days in the group not treated with steroids. The
      mortality was 6 in the steroid treated group and 5 in the non-steroid group.
      Steroids have no significant benefit on the outcome of GBS.

PMID- 9251312
TI  - Clubbing--a reevaluation of its incidence and causes.
AB  - 117 adult patients (age > 13 years) admitted in medical wards were studied for
      clubbing. 24.8% (29/117) of the patients had clubbing. Incidence of clubbing in
      males and females was 22.2% (26/117) and 2.6% (3/117) respectively [corrected].
      Liver disease, which was seen in 27.6% cases (8/29) of clubbing, was the
      commonest cause of clubbing and was observed only in males. This was related to a
      high incidence of alcohol intake among males i.e. 34.6% (9/26) as against none
      among the females. Amongst the liver disease, suppurative liver disease was
      responsible for clubbing in 75% (6/8) of cases. Only 20.7% (6/29) of patients
      with clubbing had severe clubbing. 66.6% (4/6) of patients with severe clubbing
      had liver disease. Congenital heart disease was cause of clubbing in 2 out of 3
      females (66.6%) with clubbing. Alcohol may be causally related to occurrence of
      clubbing in this part of the country.

PMID- 9251313
TI  - Cryptococcal meningitis in AIDS--need for early diagnosis.
AB  - Cryptococcal meningitis is the most common opportunistic fungal infection in
      patients with Acquired Immunodeficiency Syndrome (AIDS) contributing to the
      increased morbidity and mortality. This important infection in AIDS seems to be
      under diagnosed in India. We discuss the clinical features, laboratory diagnosis
      and therapy of seven cases of cryptococcal meningitis detected in our hospital.
      Diagnosis was established in all cases by identification of the fungus in
      cerebrospinal fluid (CSF) by India Ink preparation and positive fungal culture in
      CSF and/or Blood. Six patients were treated with Amphotericin B and Flucytosine.
      Two were cured and have not relapsed on suppressive therapy. Two died during
      treatment. Two were lost to follow up. All the three patients who died had
      positive fungal culture in blood and CSF. Presence of Cryptococcemia in
      Cryptococcal meningitis is an indicator of poor prognosis. A high index of
      clinical suspicion and routine mycological surveillance essential to identify
      this infection.

PMID- 9251314
TI  - Low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.
AB  - Twenty eight patients of myelodysplastic syndrome (MDS) were treated with low
      dose cytosine arabinoside to study the effect of this treatment modality. All
      patients presented with a hemoglobin of less than 12 Gm/dl, 4 (15%) had
      neutropenia with an absolute neutrophil count of less than 500 x 10(6)/L and 18
      (65%) had thrombocytopenia of less than 100 x 10(9)/L. The subtypes according to
      the bone marrow evaluation included 14 patients of refractory anemia with excess
      blasts (RAEB), 10 refractory anemia with excess blasts in transformation (RAEB
      T), and 4 chronic myelomonocytic leukemia (CMML). Five patients (18%) achieved
      complete hematological response, 10 (36%) had a partial response and 9 (33%)
      patients had no response. Four patients died early during treatment due to tumor
      lysis (1 CMML) and hemorrhage (3 RAEB). Seven patients progressed to acute
      myeloid leukemia (AML) while on therapy and three progressed to AML after
      completion of therapy. Five patients died of hemorrhage and 3 of septicaemia
      after achieving an objective response. The mean duration of follow up in these
      patient was 8 months (range 1 month-3 years). Only 3 patients of RAEB have
      survived for greater than 2 years. Our data reveals the short term benefit of
      this mode of therapy and emphasizes the need to develop newer therapeutic
      approaches.

PMID- 9251315
TI  - Serial blood phosphine levels in acute aluminium phosphide poisoning.
AB  - Serial blood phosphine (PH3) levels were done in patients with severe (Group I, n
      = 30), mild (Group 2, n = 10) and minimal or nil toxicity due to aluminium
      phosphide compound. Blood phosphine levels were significantly higher (p < 0.001)
      in patients of Group I than other two groups. Phosphine was not detectable in
      Group 3 patients. Therefore, blood phosphine levels were positively correlated to
      clinical grades of toxicity and to dose of active pesticide consumed. Higher the
      blood phosphine, higher was the mortality. Patients having blood phosphine levels
      equal to or less than 1.067 +/- 0.16 mg% survived, hence, it appeared to be limit
      of phosphine toxicity.

PMID- 9251316
TI  - Aerosol systems in asthma: selection and practice.

PMID- 9251317
TI  - Hepatorenal syndrome: current perspectives.

PMID- 9251318
TI  - Iron and liver: current concepts in the pathogenesis and management of chronic
      liver diseases.

PMID- 9251319
TI  - Xanthinuria--an unusual cause for renal stone disease.

PMID- 9251320
TI  - Eosinophilia and recurrent stroke.

PMID- 9251321
TI  - Hypokalemic periodic paralysis: an unusual cause.

PMID- 9251322
TI  - Filarial infection of the breast--fine needle aspiration cytology diagnosis.

PMID- 9251324
TI  - Multifocal osseous blast crisis preceding marrow blastic phase in chronic myeloid
      leukemia.

PMID- 9251323
TI  - Intracoronary ultrasound for diagnosis of left main coronary artery stenosis.

PMID- 9251325
TI  - Bochdalek hernia presentation in an adult.

PMID- 9251326
TI  - Sex influenced familial dilated cardiomyopathy.

PMID- 9251327
TI  - Surat'94: was it melioidosis?--interesting observations from the first case of
      imported melioidosis in India.

PMID- 9251328
TI  - Zoster myelitis and its response to Acyclovir.

PMID- 9251329
TI  - Treatment of visceral leishmaniasis with a 10 day course of L-ampB-LRC (Bombay),
      a liposomal amphotericin B.

PMID- 9251330
TI  - Infective endocarditis caused by Erysipelothrix rhusiopathiae in a patient with
      systemic lupus erythematosus.

PMID- 9251331
TI  - Plasmacytic ascites.

PMID- 9251332
TI  - Ophthalmoplegia in dimethoate poisoning.

PMID- 9251333
TI  - Leiomyoblastoma of G.I.T.

PMID- 9251334
TI  - Hypertrophic osteoarthropathy in Hodgkin's disease--a new entry?

PMID- 9251335
TI  - Acute respiratory failure--a rare presentation of myasthenia gravis.

PMID- 9251336
TI  - Cerebral malaria.

PMID- 9251337
TI  - Chloroquine resistant falciparum malaria--the Indian scene.

PMID- 9251338
TI  - Incidence and outcome of neurological sequelae in survivors of cerebral malaria.
AB  - This hospital based study was carried out on 185 adult patients of cerebral
      malaria. Out of 185 patients, 62 (33.5%) died and 123 (66.5%) survived.
      Neurological sequelae were present in 13 (10.5%) of 123 survivors at the time of
      discharge (i.e. 10-15 days after recovery from coma) from the hospital. These
      were in form of psychosis in 5 patients (4%), cerebellar ataxia in 4 patients
      (3.2%), extrapyramidal rigidity in 2 patients (1.62%) and hemiplegia in 2
      patients (1.62%).

PMID- 9251340
TI  - Delayed cerebellar ataxia--a complication of Plasmodium falciparum malaria.
AB  - Cerebellar ataxia is an unusual post malarial complication. We encountered 10
      patients of this disease (3 in 1992 and 7 in 1994) during the malaria epidemic
      period in Bikaner, Rajasthan. All patients were permanent residents to malaria
      endemic areas. The ataxic symptoms appeared after an afebrile period of 2-7 days.
      The neurological examination revealed no other abnormality except a cerebellar
      syndrome interfering with normal gait and speech. Lower limbs were affected more
      than the upper limbs and the mean delay between onset of fever and onset of
      cerebellar ataxia was 13 days. Peripheral blood film of all cases showed
      gametocytes of Plasmodium falciparum and in two cases schizonts of the same. All
      the patients improved within one month without any residual deficit. Further
      follow up for next 4 weeks revealed no abnormality.

PMID- 9251339
TI  - Efficacy of sulfadoxine-pyrimethamine in chloroquine resistant falciparum malaria
      in Bombay.
AB  - Several reports have confirmed the existence of chloroquine resistant Plasmodium
      falciparum malaria in Bombay. In the management of these cases, of the
      therapeutic options available, sulfadoxine-pyrimethamine (SP) (administered as a
      single dose) is preferred, since quinine has to be administered over a period of
      7 days while mefloquine is yet to be marketed in India. With increasing reports
      of falciparum malaria resistant to SP from Thailand and Africa, the present study
      was conducted to determine the efficacy of SP in the treatment of chloroquine
      resistant falciparum malaria cases in Bombay. 17 uncomplicated falciparum malaria
      patients documented to be resistant to chloroquine (10 RI, 5 RII and 2 RIII) by
      the WHO (1973) in-vivo extended field test criteria and by estimation of plasma
      chloroquine levels by High Performance Liquid Chromatography were included in the
      study. These adult patients were then treated with a supervised single dose of 3
      tablets of SP and peripheral blood smears were then repeated on days 3, 4, 5, 7,
      14, 21, 28, 35 and 42 after treatment. 14 patients responded and were sensitive
      while 3 patients showed RII grade resistance to SP. These 3 patients then
      responded to a 7 day course of quinine (30 mg/kg/day)+doxycycline (100 mg/day).
      These results thus document that SP can be used as an effective second-line
      antimalarial drug. However one should monitor the patient for plasmodial
      resistance to sulfadoxine-pyrimethamine.

PMID- 9251341
TI  - Lifestyle risk factors and coronary heart disease prevalence in Indian men.
AB  - To determine prevalence of various lifestyle coronary risk factors and their
      association with coronary heart disease (CHD) prevalence we studied 3397 Indian
      men (1982 rural, 1415 urban). A doctor-administered questionnaire, physical
      examination and electrocardiography was used. CHD was diagnosed by clinical
      history and electrocardiographic criteria. Lifestyle risk factor prevalence was:
      illiteracy 1238 (36%), nuclear family 575 (17%), crowded housing (> or = 3
      persons/room) 837 (25%), > or = 4 children 881 (26%), smoking 1554 (46%), alcohol
      intake 592 (17%), non-vegeterian diet intake 835 (25%), high fat intake 1196
      (35%), absence of prayer habit 2276 (67%), absent leisure-time physical activity
      2832 (83%) and obesity (body-mass index > or = 27 Kg/M2) 265 (8%). In rural as
      compared to urban men there was a significantly higher prevalence of illiteracy
      (39% vs 33%), crowded housing (30% vs 17%), smoking (51% vs 39%), alcohol intake
      (19% vs 15%) and high fat intake (39% vs 29%) (p < 0.01). In urban as compared to
      rural men the prevalence of nuclear family (28% vs 9%), > or = 4 children (29% vs
      24%), non-vegetarian diet intake (35% vs 17%) and sedentary lifestyle (86% vs
      81%) was more. CHD prevalence was seen in 152 (4.5%). The prevalence of CHD was
      significantly more in urban men (urban 6.0% vs rural 3.4%, p < 0.001). Odds
      ratios (95% confidence intervals) for CHD and lifestyle risk factors showed
      significant positive associations with nuclear family 1.61 (1.15-2.24), > or = 4
      children 2.10 (1.51-2.93), crowded housing 1.48 (1.04-2.10), sedentary lifestyle
      1.47 (1.00-2.25) and smoking 1.30 (1.00-1.80), and inverse association with high
      fat intake 0.42 (0.28-0.63), and not with illiteracy 0.99 (0.70-1.39), alcohol
      intake 0.84 (0.53-1.32), non-vegeterian diet 0.89 (0.61-1.29), absent prayer
      habit 1.26 (0.88-1.81), or obesity 1.42 (0.83-1.32).

PMID- 9251342
TI  - Cardiac surgery and plasma digoxin levels.
AB  - Cardiopulmonary bypass (CPB) can induce several haemodynamic alterations and
      therefore influence pharmacokinetics of various drugs. In order to assess the
      effect of CPB on plasma digoxin levels, these were monitored in patients
      undergoing open heart surgery involving CPB (n = 11), over a 24 hour period,
      starting just prior to commencement of surgery. For comparison, plasma digoxin
      was also monitored in a group of patients (n = 10) who underwent cardiac surgery
      not involving CPB. In 7 of the 11 patients in the CPB group, plasma digoxin
      levels (ng/ml) were significantly (p < 0.01) lower at the end of 24 hours (0.654
      +/- 0.094) than basal levels (1.3114 +/- 0.2498). In contrast, in the non CPB
      group, 7 of 10 patients showed significantly higher (p < 0.001) plasma levels
      (ng/ml) at the end of 24 hours (0.477 +/- 0.125) as compared to basal levels
      (0.26 +/- 0.098). Thus, rather than the type of surgery, it appears that the pre
      operative levels of plasma digoxin influence its pharmacokinetics.

PMID- 9251343
TI  - Dietary antioxidant flavonoids and coronary heart disease.

PMID- 9251344
TI  - Antioxidants and disease--current status.

PMID- 9251345
TI  - Drug induced gastrointestinal diseases.

PMID- 9251347
TI  - Unilateral agenesis of the lung.

PMID- 9251346
TI  - Spleenic abscess in a case of chronic myeloid leukemia.

PMID- 9251348
TI  - Duodenal trichobezoar presenting as intestinal obstruction.

PMID- 9251349
TI  - Ankylosing spondylitis with diverse renal outcome in two patients.

PMID- 9251350
TI  - Primary brain tumors presenting as intra cerebral haemorrhage.

PMID- 9251351
TI  - Marfan syndrome presenting as fatal ruptured dissecting aneurysm of aorta.

PMID- 9251352
TI  - Generalized myofibromatosis.

PMID- 9251353
TI  - Poisoning with fenfluramine.

PMID- 9251354
TI  - Demonstration of Lafora bodies in a patient with myoclonus epilepsy.

PMID- 9251355
TI  - Pott's paraplegia like presentation: a neurological complication of lymphatic
      filariasis.

PMID- 9251356
TI  - Severe backache during thrombolytic therapy with streptokinase.

PMID- 9251357
TI  - Leukaemoid reaction in megaloblastic anemia during puerperium.

PMID- 9251358
TI  - Terfenadine induced coma mimicking structural brain disease.

PMID- 9251359
TI  - Touch epilepsy and eating epilepsy: a common reflex centre.

PMID- 9251360
TI  - Meningeal tuberculosis secondary to an unusual primary site.

PMID- 9251361
TI  - Mefloquine induced grand mal seizure in a case of uncomplicated falciparum
      malaria.

PMID- 9251362
TI  - Headache of unusual aetiology.

PMID- 9251363
TI  - Distal renal tubular acidosis and hypokalemic paralysis--genetic and
      precipitating factors.

PMID- 9251364
TI  - Hypotensive mechanisms of captopril--a counter-view.

PMID- 9251366
TI  - Is CAPD a viable renal replacement therapy in India?

PMID- 9251365
TI  - Changing trends of communicable diseases in rural areas of western Maharashtra.

PMID- 9251367
TI  - Continuous ambulatory peritoneal dialysis: (CAPD): past, present and future.

PMID- 9251368
TI  - Continuous ambulatory peritoneal dialysis.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) was used as renal replacement
      therapy in 55 patients for 666 patient months. Thirty five patients had Type II
      diabetes. They ranged in age from 1-83 years. Majority of the patients were above
      50 years of age who could not be transplanted due to various comorbid conditions.
      The incidence of peritonitis was 1 episode every 20 patient months. Twenty five
      patients dropped out during the observation period. The major cause of drop-out
      was death due to underlying coronary artery disease. Three patients underwent
      renal transplantation.

PMID- 9251369
TI  - 'O' set connector system in CAPD.
AB  - 51 CAPD patients (age 55.5 +/- 14.5 yrs, 35 male, 16 female) on CAPD using 'O'
      set were studied retrospectively during the period January 1993 to April 1995.
      Etiology of ESRD was Diabetic nephropathy-25(49%) and the other causes-26(51%).
      The total duration of observation on 'O' set was 553 patient months, the mean
      duration was 10.8 +/- 6.1 months. 24 patients (47%) developed total of 30
      episodes of peritonitis. The incidence of peritonitis was 18.4 patient months per
      episode of peritonitis. The organisms responsible for peritonitis were Gram
      positive-6(20%), Gram negative-3(10%), Fungal-1(3.3%), Mycobacterial-1(3.3%),
      Eosinophilic-1(3.3%), Sterile-12(40%) and unknown-6(20%) 2 patients of bacterial
      peritonitis and a patient with tuberculous peritonitis died while rest of the
      patients responded favourably to antibiotics. 13(52%) diabetic patients and
      11(42%) non-diabetic patients had peritonitis (p-NS) and the peritonitis rates in
      diabetics and non diabetics were 18.3 and 18.6 patient months per episode
      respectively (p-NS). Exit site infection was seen in 5 patients (10%) (Staph
      aureus-4, Enterococci-1) and all responded to antibiotic therapy. 7 patients had
      total of 10 episodes of symptomatic accidental intraperitoneal sodium
      hypochlorite instillation, none had any long term adverse effects. The 'O' set
      procedure was done by self in 10(20%) and by others in 41(80%) cases. The
      peritonitis rates when performed by self and others were 18.5 and 18.4 patient
      months per episode respectively (p-NS). The cost of being on CAPD using 'O' set,
      Y-bag and twin bag were Rs. 1,50,000, 2,10,000 and 3,72,000 per annum
      respectively and cost of maintenance haemodialysis was 1,36,800 per annum. The
      cost of CAPD using 'O' set was comparable to that of maintenance haemodialysis.
      The 'O' set connector system in CAPD is found to be safe, cost effective and
      efficient.

PMID- 9251370
TI  - Direct agglutination test for early diagnosis of Indian visceral leishmaniasis.
AB  - In a prospective study, 80 cases of fever with hepatosplenomegaly, anemia and
      leucopaenia coming from the hyperendemic zones for visceral leishmaniasis of
      North-Bihar, India were screened and subjected to bone marrow or splenic puncture
      for demonstration of Leishman-donovan bodies (LDB) and DIRECT AGGLUTINATION TEST
      (DAT) with antigen prepared by Harith et al. 59 cases were confirmed for Visceral
      Leishmaniasis (VL) by demonstration of LDB in which DAT was also positive in
      different titres ranging from 1:1600 onwards. Out of 21 cases in which the bone
      marrow was negative for parasite, DAT was positive in 10 cases. 8 Out of 10 cases
      responded to WHO regimen of treatment with sodium stibogluconate (SSG). Remaining
      two cases who did not respond to this therapy became positive for parasites on
      subsequent splenic aspirate. They were treated with pentamidine isethionate and
      were cured. 11 out of 80 cases showing a titre of 1:400 or lower in DAT, 6 proved
      to be cases of enteric fever and 5 of malaria. Thus DAT using Harith's antigen
      was found to be 100% sensitive and specific in detection of early cases of Indian
      VL.

PMID- 9251371
TI  - Comparative merits of different tissue biopsies in the diagnosis of sarcoidosis:
      Indian perspective.
AB  - In sarcoidosis, diagnosis rests on positive tissue biopsy in association with
      suggestive clinical features. In absence of guidelines in India, multiple
      biopsies (494 in total) were undertaken from 170 suspected and later proven cases
      of sarcoidosis. Involved tissues, Kveim test site, right scalene node, palpable
      peripheral lymph nodes and open pulmonary biopsy gave 80-100% positive result.
      (Perbronchial lung biopsy proved positive in India by other workers.) Mantoux
      test site, a rather unusual tissue, even if negative at 72 hours, may show
      positive granuloma in 64.5% cases with active sarcoidosis. Positive liver biopsy
      has only corroborative importance.

PMID- 9251372
TI  - Comparison of biochemical parameters in pleural effusion.
AB  - A comparison of various biochemical parameters used in differentiation of nature
      of pleural effusion in transudate and exudate was done in 84 patient of pleural
      effusion. Pleural fluid (P) cholesterol and bilirubin which have gained an
      importance in recent years were compared with pleural fluid protein, LDH, P/S
      protein, P/S LDH and Light's criteria. It was seen that Light's criteria is still
      the best in differentiation. Sensitivity of individual test was nearly same for
      Pl. protein (94.11%), P/S Protein (94.11%), Pl. LDH (95.5%), P/S LDH (92.75%). Pl
      cholesterol (88.3%) and P/S cholesterol (91.42%) had slightly lower sensitivity.
      Pl. Protein and P/S LDH had 100% specificity. Lights criteria had 100%
      specificity and sensitivity % of cases misclassified by various criteria were Pl
      Protein 5.95%, P/S protein 5.95%, PLDH 4.76%, P/S LDH 4.76% P. Cholesterol 13%
      and P/S Cholesterol 9.52% Measurement of Bilirubin did not provide any
      correlation in classifying the effusion and thus did not hold any value.

PMID- 9251374
TI  - Present status of drug resistance in cases of enteric fever in Rajasthan.
AB  - Drug Sensitivity of Salmonella typhi isolated from 30 blood culture positive
      cases of typhoid fever who presented between Nov. '93 to Aug. '94 was tested to
      determine their in vitro susceptibility to various antimicrobiols. 56.6% showed
      resistance to chloramphenicol, 70% to amoxycillin, 50% to amikacin, 43.3% to
      gentamycin, 40% to ampicillin, 33.3% to cotrimoxazole, 30% to cephalexin and very
      low resistance (6.6% each) to ceftriaxone and cefotaxime. All the 30 cases were
      sensitive to ciprofloxacin and ofloxacin. 17 chloramphenicol resistant typhoid
      cases in whom chloramphenicol was initially started failed to respond to this
      drug even after 4-5 days therapy, indicating that in vivo response matched with
      the in vitro sensitivity. Clinical response to ciprofloxacin, whether given
      initially or following chloramphenicol failure was prompt and satisfactory.
      Ciprofloxacin thus appears to be a good choice in such cases.

PMID- 9251373
TI  - Experience with roxithromycin in visceral leishmaniasis in north Bihar.
AB  - In search of an oral drug for Visceral Leishmaniasis, 54 cases of Kala-azar were
      treated with roxithromycin, an orally administrable drug at a dose of 300 mg
      twice daily for 21 days. Thirty-nine (86.7%) were responsive (cured), 11 (28.2%)
      relapsed. The results appeared equally or even more effective when compared to
      the sodium antimony gluconate in two recent trials in Kala-azar in almost same
      demographic pattern. A possible synergistic action of roxithromycin and SAG was
      explored. Toxicities of SAG and roxithromycin are compared and discussed. Further
      controlled trials are needed before it can be widely used as first line drug for
      Indian Kala-azar in the present epidemic.

PMID- 9251375
TI  - High resolution computed tomography of the lungs.

PMID- 9251376
TI  - Pregnancy outcome in systemic sclerosis.
AB  - The outcome of pregnancy in systemic scleroderma (SSc) has been a subject of much
      interest. In a retrospective analysis of 59 pregnancies of 17 mothers with SSc,
      the effect of disease on pregnancy outcome was variable. There was no adverse
      effect on fertility. While there was an apparent decrease in fertility in the
      limited cutaneous disease, this was not seen in the diffuse variety. There was an
      decreased incidence of live birth after the onset of disease as compared prior to
      the onset of disease. The foetal wastage after the onset of disease was
      contributed equally by spontaneous abortions as well as induced terminations of
      pregnancies. The presence of anticardiolipin antibodies was not related with
      adverse outcome. The effect of pregnancy on disease was variable with the disease
      being stable in five patients, regressing in five and progressing in three. The
      increased terminations of pregnancy reflects the uncertainities of positive
      outcome both by parent and attending physicians.

PMID- 9251377
TI  - Alprazolam in chronic tension type headache.
AB  - Alprazolam was evaluated in the treatment of 62 patients of chronic tension type
      headache using a double blind cross over design with random allocation to drug or
      placebo. The duration of the trial was 4 months with a 2 week run in period and 2
      week washout period separating two treatment periods of 4 weeks each. The
      patients were followed up for 4 weeks at the completion of the trial. 48 patients
      completed the trial. There was no significant difference in the overall response
      rate based in terms of percentage reduction in headache frequency per week,
      however a significant decrease in headache index was observed during treatment
      with alprazolam as compared to placebo (P < 0.05). The mean analgesic intake per
      week was also significantly lower during treatment with alprazolam as compared to
      the run in period. Side effects were seen in 16.67% patients. In none of the
      patients was it significant enough to require withdrawal from the study.

PMID- 9251378
TI  - Clinical and demographic features of Meige's syndrome.
AB  - Fifty five patients with Meige's syndrome were examined for clinical and
      demographic features. The mean age of onset was 52.3 years. The peak age of onset
      was in the sixth decade with a male to female ratio of 1.11:1. The mean duration
      of illness was 3.7 years. Commonest initial symptom was increased blinking, seen
      in 30 cases (54.5%). Twenty five patients (45.4%) had complete syndrome of
      blepharospasm with oromandibular dystonia, whereas 24 patients (43.6%) had
      blepharospasm alone and the rest (6 patients, 10.9%) had oromandibular dystonia.
      The extension of spasm beyond cranial muscles was observed in 10 patients
      (18.1%). Eleven patients had family history of dystonia or other extrapyramidal
      disorders. Incidence of depression was high in these cases.

PMID- 9251379
TI  - Three dimensional echocardiography: from the realm of research to clinical
      reality.

PMID- 9251380
TI  - Spontaneous resolution of a pituitary mass: probable lymphocytic hypophysitis.

PMID- 9251381
TI  - Primary colorectal lymphoma.

PMID- 9251382
TI  - Arachnoid cyst with type I Arnold Chiari malformation presenting as syringomyelic
      syndrome.

PMID- 9251383
TI  - Simultaneous phenytoin and warfarin toxicity on chronic concomitant therapy.

PMID- 9251384
TI  - Adult moyamoya disease.

PMID- 9251385
TI  - Sternal tenderness in falciparum malaria.

PMID- 9251386
TI  - Animal bites in India.

PMID- 9251387
TI  - Steroids/dexamethasone in adults with bacterial meningitis.

PMID- 9251388
TI  - Hepatitis B: the lurking danger.

PMID- 9251389
TI  - Posterior mediastinal mass.

PMID- 9251390
TI  - HIV/AIDS epidemic in India: the past decade (1986-96) and future scenario.

PMID- 9251391
TI  - A comparative study of the awareness and attitude of HIV/AIDS among students
      living in India and migrants to the United States.
AB  - The goal of the current study was to collect preliminary data regarding HIV/AIDS
      awareness among Indian students who are residing in India and those who have
      migrated to the United States. A questionnaire was distributed to thirty-four
      college students in the United States and thirty-eight college students who are
      residing in India, between ages 18-26 years. 74% of the Indian group and 53% of
      the USA group felt that their knowledge of this disease is not adequate. 3% felt
      that this disease is completely curable. Only 13% of the Indian group and 23% of
      the USA group thought that tuberculosis is linked to HIV infection. Both groups
      felt that the newspapers and magazines are good sources of information. The
      majority of the Indian (71%) and USA (50%) groups felt that HIV/AIDS education
      should begin in high school. 90% of the Indian group and 79% of the USA group
      felt that people in India do not have adequate knowledge about AIDS. The majority
      felt that the high-risk population should be screened and there should be more
      governmental support.

PMID- 9251393
TI  - Low prevalence of hepatitis C viral infection in patients with non-alcoholic
      chronic liver disease in India.
AB  - To investigate the prevalence and profile of chronic liver disease due to
      hepatitis B (HBV) and C (HCV) infection in patients with non-alcoholic chronic
      liver disease in North India, 148 biopsy proven patients (73 with a history of
      transfusion and 75 non-transfused) were studied. Detection of hepatitis B
      included HBsAg, AntiHBc, and HBV DNA testing. Presence of HCV infection was
      investigated by EIA using second generation tests and confirmed by RIBA III and
      HCV RNA testing. Eighty three (56.1%) patients had cirrhosis related to hepatitis
      B, 13 (15.7%) of them had precore (HBeAg -ve, HBVDNA +ve) and 11 (13%) had
      surface (HBsAg-ve, IgM antiHBc-ve, HBVDNA +ve) mutation. Antibodies to HCV were
      found in 16 (10.8%) patients. Dual infection with HBV and HCV was seen in 20
      (13.5%) patients. Twenty nine (19.5%) patients, had cryptogenic cirrhosis as none
      of the markers for HBV or HCV infection was positive. In conclusion, our results
      demonstrate that HBV was the most prevalent viral infection associated with
      chronic liver disease patients in North India. Prevalence of HCV infection was
      low. Studies to detect HBV mutants and other viruses should be done in patients
      with suspected cryptogenic cirrhosis of the liver.

PMID- 9251392
TI  - Renal involvement in multiple myeloma.
AB  - The present study is a retrospective chart analysis of 33 patients who satisfied
      the diagnostic criteria of multiple myeloma. Sixteen (49.5%) of these 33 patients
      developed renal failure at some point in time. The mean age +/- 1SD of patients
      who developed renal failure was 59.2 +/- 13 years (range 34-85 years). There were
      12 males and 4 females. The precipitating factors for renal failure were
      dehydration (12.5%), hypercalcemia (62.5%) and use of non-steroidal
      antiinflammatory drugs (6.2%). Hypercalcemia was observed in 10 of the 16
      patients who developed renal failure while it was seen in only 4 of the 17 cases
      who did not develop renal failure (relative risk 5.4). In 11 (68.7%) patients,
      the renal function improved with hydration, treatment of hypercalcemia and
      chemotherapy. The 1 and 3 year actuarial survival of patients with renal failure
      and multiple myeloma was 87% and 74% respectively.

PMID- 9251394
TI  - A prospective study of delta infection in fulminant hepatic failure.
AB  - Thirty one patients of HBV related Fulminant Hepatic Failure (FHF) were studied
      for the presence of delta infection and subsequently the clinical features,
      course and outcome of the delta infected cases was compared with those of delta
      uninfected cases. Out of 31 patients studied, 11 patients (35.8%) were reactive
      for anti-delta antibodies. There was no significant difference in age in delta
      reactive and non-reactive group. Hepatic encephalopathy was seen in all of the
      patients. The mean SGOT and SGPT were 378 +/- 88.74 U and 454 +/- 70.44 U
      respectively in anti-delta reactive group as compared to 239 +/- 74.94 U and
      274.1 +/- 100.34 U respectively in anti-delta non reactive group (p < 0.05).
      During follow up, 10/11 patients (91%) died in anti-delta reactive group as
      compared to 13/20 patients (65%) in anti-delta non reactive group. So this study
      suggests that delta virus infection is quite common in India and it lead to
      excerbation of illness and carries a relatively poor prognosis for FHF.

PMID- 9251395
TI  - Clinical observations on tropical men during their sojourn over the Arctic
      region.
AB  - In the present study, besides a detailed clinical evaluation, roentgenographic
      changes in cardio-respiratory system in Indian soldiers (IS) during their 60 days
      stay at the arctic have been observed. These results have been compared with the
      responses at Delhi (before cold acclimatisation) and on return to Delhi
      (deacclimatisation). An attempt has also been made to compare the same
      physiological variables with those of Russian Migrants (RM) and Russian Natives
      (RN) in the arctic region to review significant differences if any. Heart Rate
      (HR) did not show much change; there was a tendency to increase in both systolic
      and diastolic blood pressure; and Kerdo's index inclined towards increased
      sympathetic activity in IS. X-ray chest (PA View) did not show any appreciable
      change in the lungs in the three groups. One subject amongst IS showed cardiac
      enlargement and RN subjects showed prominence of pulmonary artery and pulmonary
      vascular markings. All these physiological changes aim at increasing the cardiac
      output to overcome the ill effects of cold. Pneumopathy, a clinical condition of
      increased pulmonary haemodynamics could have resulted in the prominence of
      pulmonary artery and pulmonary blood flow in the RN. Most of the physiological
      changes reverted to the baseline value on return to Delhi thus proving that there
      were no permanent changes during short stay at extreme cold conditions.

PMID- 9251398
TI  - Evolving myocardial infarction--diagnosis and management.

PMID- 9251397
TI  - A multicentric prescription event monitoring study of Verorab.

PMID- 9251396
TI  - The role of VP-16 in autologous bone marrow transplantation for acute
      myeloblastic leukemia.

PMID- 9251399
TI  - Nephrologic aspects of HIV infection.

PMID- 9251400
TI  - Coronary reperfusion injury.

PMID- 9251401
TI  - Atherosclerosis in transplant heart.
AB  - Graft atherosclerosis in the transplant heart is essentially asymptomatic due to
      denervation of the transplant heart and also is rapidly progressive. After one
      year it is the major cause of transplant rejection. Histopathologically, graft
      atherosclerosis differs from the conventional atherosclerosis. Intra-vascular
      ultrasound and repeated coronary angiography help in its early diagnosis.
      Angioplasty and bypass graft surgery are not of much help. Preventive measures
      through dietary means to keep triglycerides under control and prophylactic use of
      calcium channel blocker, diltiazem are rewarding. Many patients with graft
      coronary atherosclerosis end up with retransplant.

PMID- 9251402
TI  - Pregnancy associated aplastic anaemia.

PMID- 9251403
TI  - Thrombotic thrombocytopenic purpura in a patient with diffuse scleroderma.

PMID- 9251404
TI  - Klippel Trenaunay syndrome: a case involving both lower limbs in association with
      Marfanoid habitus.

PMID- 9251405
TI  - Melanotic neuroectodermal tumour of infancy: immunohistochemical and histogenetic
      consideration.

PMID- 9251406
TI  - False negative ELISA in an Indian truck driver with AIDS.

PMID- 9251407
TI  - Hepatic sequestration crisis presenting with severe intrahepatic cholestatic
      jaundice.

PMID- 9251408
TI  - Cerebral infarction in Wolff-Parkinson-White syndrome.

PMID- 9251409
TI  - Atypical case of tuberculosis of stomach presenting as gastric outlet
      obstruction.

PMID- 9251410
TI  - Organophosphate compound poisoning and cardiac toxicity.

PMID- 9251411
TI  - Adrenal insufficiency in India.

PMID- 9251412
TI  - Lignocaine toxicity following pleurodesis.

PMID- 9251413
TI  - Allergy to human insulin.

PMID- 9251414
TI  - Ephedrine-saline nasal wash in allergic rhinitis.

PMID- 9251415
TI  - Cigarette withdrawal syndrome.

PMID- 9251416
TI  - Coarctation of aorta and hereditary spherocytosis.

PMID- 9251417
TI  - Physical exercise as prevention of CHD.

PMID- 9251418
TI  - Adenocarcinoma of the lung--pleomorphic radiographic appearances.

PMID- 9251419
TI  - The cross match test--even more important than tissue typing in renal
      transplantation.

PMID- 9251420
TI  - Transesophageal echocardiography--complimentary or competitive? [ editorial;
      comment].

PMID- 9251421
TI  - Crossmatching considerations in renal transplantation.
AB  - During the year 1993-1994, 73 renal transplant cases have been screened for the
      presence of anti-HLA antibodies using the standard lymphocytotoxicity assay.
      Amongst the 9 related transplantations with 100% negative crossmatch 6 were
      successful. About 8.2% of the patients had a shift from positive to negative
      crossmatch. It was observed that an increased number of transfusions (ranging
      from 3 to 21) in males and females yielded negative crossmatches. In females,
      however, owing to various factors such as pregnancies, parity and infections,
      varied percentages were observed with different donors. The crossmatches in
      diabetics and hypertensive patients suggest no particular correlation and
      probably have no role in the outcome of the assay.

PMID- 9251422
TI  - Studies on prosthetic valve function--a transesophageal echocardiographic
      assessment.
AB  - Haemodynamic assessment was done by colour flow mapping and Doppler interrogation
      by both Transthoracic (TTE) and Transesophageal echocardiography (TEE) in 40
      consecutive patients (mean age 36.6 +/- 12.35 years) with prosthetic valves.
      There were 30 cases of mitral (MVR) and 12 aortic (AVR) valve replacement. Major
      purpose of the study was to detect the sensitivity of TEE in detecting prosthetic
      valve malfunction particularly in comparison to TTE. Pannus was detected in 3 and
      8 cases of MVR (p < 0.01) by TTE and TEE respectively; however, TEE was found to
      be of equal status in detecting pannus over AV (2 cases). Physiological
      regurgitation in MVR and AVR was detected in 13% and 25% by TTE and 20% and 33%
      by TEE respectively. Paravalvular leak was detected in 3 cases of MVR by TEE
      compared to only case by TTE. Though it is difficult to deduce any specific
      conclusion from this small number of patients, there is definite trend to higher
      sensitivity in detecting disorders with TEE specially for mitral prostheses.

PMID- 9251423
TI  - Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12
      gm infusion) in the management of organophosphorus poisoning.
AB  - Organophosphorus (OP) poisoning is most frequently encountered among our
      community. Treatment of poisoning is primarily aimed at reversing the effects of
      the compound by administration of atropine. Oximes have been shown to be
      efficacious in case reports. The dose of this drug in these reports varies from 1
      gm which is a very low dose and physiologically no dose, to doses upto 16 gm.
      This is also a very expensive imported drug which causes the nation considerable
      loss of foreign exchange. We report our experience with the use of two treatment
      regimens of Pralidoxime (P2AM) in the management of patients with OP poisoning in
      a prospective trial. Seventy-two adult patients presenting to a large university
      affiliated teaching institution with a history of consumption of OP compounds and
      requiring intensive care were entered into the trial. Patients were randomized
      using a block randomisation to receive either a single bolus dose of 1 gm P2AM at
      admission (Low dose group) followed by placebo infusion over the next 4 days or a
      single placebo bolus at admission followed by P2AM 12 gm as a continuous infusion
      over the next 4 days. Outcome measures analyzed were mortality, duration of ICU
      stay, need for ventilation and duration of ventilation, time to recovery of
      consciousness, development of intermediate syndrome and infections. A higher
      prevalence of intermediate syndrome (p = 0.08) was observed in the high dose
      group. Ventilatory requirement was also more in the high dose group (p = 0.09).
      Since this was an equivalence study designed to show that the low dose was as
      effective as the high dose, these results attain greater significance as the low
      dose group fared better than the high dose group, even though the pre-test
      hypothesis was in the reverse direction. Subgroup analysis of patients who
      received at least 1 gm of P2AM within 12 hours of ingestion of the OP poison with
      those who received P2AM after 12 hours, showed that there was a significant
      reduction of intermediate syndrome (p = 0.05) but no significant difference was
      noted in number ventilated. High dose P2AM infusion has no role in the routine
      management of patients with OP poisoning. These results also suggest that the
      time of administration of P2AM after the ingestion of the poison mabe a crucial
      factor which determines response to therapy. A prospective double blind placebo
      controlled trial is now justified in the light of the above findings.

PMID- 9251424
TI  - Injection induced nerve injury : an iatrogenic tragedy.
AB  - 11 patients with injection induced nerve injury were evaluated. There were 9
      adults and 2 children, 8 had radial nerve injury and 3 sciatic nerve injury. 6
      had evidence of severe involvement with active denervation. Nature of the drug
      was not known in 81%, thus faulty site of injection was the most important factor
      responsible. The need to discourage indiscriminate use of intramuscular
      injections and choice of a proper site of selection is stressed.

PMID- 9251425
TI  - Clinical assessment of autonomic functions in anemics.
AB  - Sixty five anemics and 20 healthy control subjects carefully age and sex matched
      were subjected to seven standardised tests to evaluate autonomic status. Due care
      was taken to remove factors which could interfare with the results. Tests
      concerned with the basal parasympalhetec tone viz heart rate response to standing
      (p < 0.001) and intravenous atropine test (p < 0.05) showed significant
      difference which persisted with severity and type of anemia. Test requiring
      stimulation of the parasympathatic system i.e. deep breathing test, valsalva
      maneuver and carotid sinus massage did show not significant difference. No
      difference of significance was found with postural fall of blood pressure and
      sustained hand grip test, chiefly concerned with the sympathatic system. These
      results suggest that anemics have low basal parasympathatic outflow to increase
      the heart rate as compensatory mechanism. Stimulation of parasympathatic and
      sympathetic system arouse normal response.

PMID- 9251426
TI  - Ultrasonic evaluation of portosystemic collateral circulation in portal
      hypertension.
AB  - The aim of the study was to evaluate portosystemic collateral circulation in
      relation to (1)individual etiological groups of portal hypertension., (2)
      Presence and size of esophageal varices, (3) esophageal sclerotherapy and (4)
      ascites. A prospective study of 101 patients of portal hypertension was carried
      out. Patients were divided into 4 etiological groups: Alcoholic cirrhosis (ALD)
      (38), Non-alcoholic cirrhosis (NALD) (35), non cirrhotic portal fibrosis (NCPF)
      (14) and extrahepatic portal vein obstruction (EHPVO) (14). Esophageal varices
      were assessed and graded endoscopically into 3 categories: no varix, small
      varices and large varices. Evaluation of portosystemic collateral circulation,
      other than esophageal varices was done ultrasonically. "Other" portosystemic
      collaterals (lienorenal, gastrorenal, dilated paraumbilical and umbilical veins,
      paraduodenal and gall bladdes varices) were seen in 26 out of 101 patients and
      more commonly in the non-cirrhotic groups (50%) [NCPF: 57.14%, EHPVO: 42.86%]
      than in the cirrhotic group (16.44%) [ALD: 13.5%, NALD: 20%]. Gall bladder
      varices were the only form of ectopic (extra esophagogastric) varices visualised
      with an overall incidence of 3.96%. Collateral shunts were seen more frequently
      in patients without varices (100%), than in patients with small varices (34.88%)
      or large varices (7.84%), and in patients having undergone esophageal
      sclerotherapy (57.14%). Collateral circulation did not contribute to the
      development of ascites. 37 patients with ascites did not have collateral shunts.
      We conclude portosystmic circulation plays a decompressive role in portal
      hypertension and prevents formation of esophageal varices or prevents them from
      increasing in size. It is seen more frequently in noncirrhotic patients and in
      those having undergone sclerotherapy and does not contribute to development of
      ascites.

PMID- 9251427
TI  - Health problems in rural elderly at Varanasi, Uttar Pradesh.
AB  - Present study comprised of 1070 elderly patients coming to P.H.C. Bhopauli,
      Varanasi during January 1991-December 1992. Males were 578 and females were 492.
      Male predominance was present in younger elderly whereas female predominance was
      seen among those over 75 years of age. Socio-economic status-wise 265 cases
      belonged to upper, 394 middle and 411 to lower income group. Arthritis (615) was
      the commonest disease in elderly followed by hypertension (510), visual problems
      (400), ischaemic heart disease (IHD) (350), hearing impairement (300), diabetes
      mellitus (DM) (280), protozoal and worm infestations (240), chronic bronchitis,
      asthma, emphysema (238), tuberculosis (220), peptic ulcer syndrome (210),
      varicose vein (200), haemorrhoids (180), urinary problems (154). Two hundred and
      forty seven cases had 2 diseases followed by 3 diseases (239), 4 diseases (165),
      5 diseases (127) and more than 5 diseases (81). Multiple diseases were more
      frequent among those above 75 years of age. Atypical presentations and
      complications of different diseases were more frequent among older elderly.

PMID- 9251428
TI  - Evaluation of serum lipids in patients of acute stroke.
AB  - Stroke, though considered a thromboembolic disorder, is known to be associated
      with hyperlipidaemia. In Western country, some workers have performed studies
      exploring the role of lipids in stroke in their country. Such a study is lacking
      in Indian population. This study was therefore conducted to observe the role of
      lipids in stroke by evaluating 13 parameters of lipids in 48 patients of non
      haemorrhagic cerebral stroke hospitalised in acute condition and compared with
      those of 70 age matched normal subjects. Results revealed that phospholipids and
      arachidonic acid were significantly altered in patients of acute stroke.

PMID- 9251429
TI  - Echocardiographic changes and alterations in lipid profile in cases of
      subclinical and overt hypothyroidism.
AB  - Forty four patients (22 of overt hypothyroidism and 22 of subclinical
      hypothyroidism) and 11 controls underwent lipid profile evaluation and two
      dimensional echocardiography. Amongst the various parameters evaluated, mean
      Interventricular Septal (IVS) dimensions were significantly (p < 0.005) raised in
      overt hypothyroidism [IVS: end diastolic (ED) = 0.973 +/- 0.223 cm.; end systolic
      (ES) = 1.300 +/- 0.240 cm.] with respect to control group [IVS : ED = 0.747 +/-
      0.118 cm.; ES = 1.073 +/- 0.173 cm.]. Mean Left Ventricular Posterior Wall (LVPW)
      thickness was also significantly (p < 0.005) raised in overt hypothyroidism [LVPW
      : ED = 0.944 +/- 0.200 cm.; ES = 1.350 +/- 0.243 cm.] in comparison with control
      group [LVPW : ED = 0.779 +/- 0.091 cm.; ES = 1.176 +/- 0.128 cm.]. Evidence of
      diastolic dysfunction was present in both subclinical (n = 2) and overt
      hypothyroidism (n = 6) while pericardial effusion was seen only in overt
      hypothyroidism (n = 10). Mean Serum cholesterol was significantly raised in both
      subclinical (192.13 +/- 47.40 mg%) (p < 0.05) and overt hypothyroidism (231.27 +/
      68.30 mg%) (p < 0.005) with respect to control group (157.63 +/- 37.69 mg%). In
      overt hypothyroid patients mean serum Triglyceride (235.59 +/- 137.53 mg%) (p <
      0.05), LDL (126.09 +/- 54.99 mg%) (p < 0.05) and Apo-B (0.698 +/- 0.354 g/L) (p <
      0.05) levels were significantly higher as compared to control group (serum
      triglyceride 165.45 +/- 49.15 mg%, LDL 88.72 +/- 38.75 mg%, Apo-B 0.474 +/- 0.176
      g/L.

PMID- 9251430
TI  - Microbial resistance: global implications and strategies for combat.

PMID- 9251431
TI  - Lumbosacral radiculopathy and hemophilia.

PMID- 9251432
TI  - Multiple Salmonella typhi subcutaneous abscesses in a sickle cell anaemia
      patient.

PMID- 9251433
TI  - Malignant chondroid syringoma of scalp with cervical lymph node metastases.

PMID- 9251434
TI  - Acute pseudobulbar mutism: a patient with an unusual stroke syndrome associated
      with good functional recovery.

PMID- 9251435
TI  - Opponensplasty--a rare complication and its prevention.

PMID- 9251436
TI  - Acute disseminated histiocytosis X presenting with frightening proptosis in an
      adult.

PMID- 9251437
TI  - Trismus associated with hypokalemic periodic paralysis.

PMID- 9251438
TI  - Tubercular splenic abscesses in a patient with AIDS.
AB  - Opportunistic infections are common in patients with AIDS. There is an increasing
      incidence of tuberculosis, especially extrapulmonary tuberculosis. Splenic
      abscesses is one such, though rare, extrapulmonary manifestation. We report such
      a case discuss the diagnosis and treatment in these cases.

PMID- 9251439
TI  - Salmonella infection mimicking acute rheumatic fever.

PMID- 9251440
TI  - Biphasic spirogram in unilateral mainstem bronchus obstruction--the "two can"
      filling effect.

PMID- 9251441
TI  - Oral transmission of rabies in cow: milk consumers protected by immunisation.

PMID- 9251442
TI  - Iron absorption in Indians.

PMID- 9251443
TI  - Acute inflammatory demyelinating polyradiculoneuropathy following antirabies
      vaccine.

PMID- 9251444
TI  - Clinical profile of stroke in relation glycemic status of patients.

PMID- 9251445
TI  - Clubbing reevaluation--a minor statistical mistake!

PMID- 9251446
TI  - Osteoporosis--India: emerging message.

PMID- 9251447
TI  - Multiple sclerosis.

PMID- 9251448
TI  - Multiple sclerosis in India: A.I.I.M.S. experience.
AB  - Fifty patients of multiple sclerosis were reviewed. The commonest initial
      neurologic symptom was motor weakness (30%) followed by visual impairment (26%).
      Absence of internuclear opthalmoplegia was noted in addition to the infrequent
      occurrence of optic nerve involvement and Devic's disease. Evoked potential
      studies and radiological investigations were in agreement with others series
      reported.

PMID- 9251449
TI  - Infections in the immunocompromised host: a prospective multicenter survey in
      patients receiving chemotherapy for acute leukemia.
AB  - Patients receiving chemotherapy for acute leukemia were prospectively followed up
      to determine the frequency, nature and outcome, of episodes of infection during a
      6 or 12 month period at each of the participating centres. A total of 605 cycles
      of chemotherapy were surveyed. Of these, 490 cycles were received by patients
      with acute lymphoblastic leukemia (ALL) and 115 by patients with acute non
      lymphoblastic leukemia (ANLL). 241 episodes of infection were recorded during the
      survey: 179 among ALL patients and 62 among patients of ANLL. Infections were
      more common during chemotherapy for ANLL than for ALL, occurring in 54% (62/115)
      and 36% (179/490) of chemotherapeutic cycle respectively. A favorable response to
      empiric antibacterial agents was seen in 39% (23/59) of episodes in ANLL patients
      and 77% (134/174) of episodes among ALL patients. Infection presented as fever of
      unidentified origin in an overwhelming majority (63%) of episodes.
      Gastroenteritis and pneumonia occurred with a frequency of 11% and 10% while the
      frequency of all other diagnoses was 3% or less. Overall, E coli and Candida were
      the most frequently isolated organisms while Staphylococcus aureus and Group A
      Streptococci were the most frequent isolates from blood and throat swabs,
      respectively. A high degree of resistance to commonly used antimicrobial agents
      was seen among the most frequently isolated organisms. About 75% of episodes of
      infection which did not respond to antibacterial agents responded to empiric
      systemic antifungal therapy; although fungi were mycologically isolated in only a
      quarter of these instances. Oropharyngeal candidiasis occurred in association
      with 3% of chemotherapeutic cycles.

PMID- 9251450
TI  - Prevalence of asymptomatic electrocardiographic abnormalities in a rural
      population.
AB  - To determine the prevalence of various electrocardiographic (ECG) abnormalities
      among asymptomatic individuals in a rural population of India we performed a 12
      lead ECG during a comprehensive cardiovascular survey in three randomly selected
      villages in Rajasthan. Twenty four of 3148 individuals with a past diagnosis or
      symptoms suggestive of coronary heart disease (CHD) were excluded. ECG of 3124
      persons (males 1965, females 1159) were analysed and classified according to the
      WHO-Minnesota Code. The prevalence rate/1000 of Q-waves was 8.6 (males 8.7,
      females 8.6) and ST-T wave changes was 17.0 (males 12.7, females 24.2). An age
      related increase in prevalence of Q-waves was seen (X2 for trend p < 0.01). The Q
      wave prevalence was similar among males and females but ST-T changes were more
      frequent in females (p = 0.0016). Other prevalent findings were left ventricular
      hypertrophy in 8.3, right or left bundle branch block pattern in 18.6, left or
      right axis deviation in 10.6, atrioventricular conduction defects in 10.2 and
      ventricular arrhythmia in 1.3/1000 population.

PMID- 9251451
TI  - Critical evaluation of references in drug advertisements: an Indian experience.
AB  - Drug advertisements have important effect in prescribing habits of physicians.
      WHO states that all the claims in drug advertisements should be supported by
      suitable documentary evidences (references). The present study evaluated
      citations (mentioned/not mentioned), sources (journals, books,
      conferences/symposia, personal testimonial, unpublished data in file) and
      adequacy (complete/incomplete) of the references in 585 drug advertisements
      supplied by medical detail persons to different clinical departments of our
      hospital. The references were cited only in 37.9% of the drug advertisements. In
      total, 1032 references (76% of journals, 15% of books, 2% of
      conferences/symposia, 4% of personal testimonials, 1% of unpublished data and 2%
      of data in file) were cited. Only 10% references of journals, 7% of books and 12%
      of conferences/symposia were found complete (according to standard bibliographic
      norms). The current situation can be improved if the government, industry and the
      prescribers formulate some guidelines for the mentioning of adequate references
      in drug advertisements.

PMID- 9251452
TI  - Comparison of sodium nitroprusside added peritoneal dialysis and standard
      haemodialysis.
AB  - Thirty patients of acute or acute on chronic renal failure (ACRF) were randomly
      divided into two group of 15 cases each. Group A patients received 36 cycles of
      intermittent peritoneal dialysis (PD) with an exchange volume of one litre and
      duration of one hour per cycle. The 36 cycles of PD were divided into 12
      clearance periods of 3 cycles each. Sodium Nitroprusside (SNP) was added in a
      dose of 4 mg/litre of dialysate in alternate clearance periods. Group B patients
      were given 4 hours of haemodialysis (HD) to compare the efficacy of two modes of
      dialysis. Symptomatic relief was observed in various uraemic signs and symptoms
      like vomiting, level of consciousness, fluid overload, hiccough and asterexis in
      most of the patients in both the groups. The percentage fall in blood urea and
      serum creatinine was 57.02 Vs 58.04 mg% and 46.9 Vs 47.8 mg% in group A and B
      respectively (P 70.5 each). Total dialysate urea removal following PD and HD was
      118.8 +/- 57.3 gm and 98.5 +/- 37.0 gm respectively and also there was no
      significant difference in total creatinine removal. No untoward effects were
      observed with PD. However, following HD, 5 patients developed hypotension,
      supraventricular tachycardia was observed in one and disequilibrium syndrome in 8
      of them. Therefore, it can be concluded that SNP added PD is comparable to 4
      hours of haemodialysis both clinically as well as biochemically and in situations
      where facilities for HD do not exist or it is contraindicated, PD may be
      preferred mode of therapy.

PMID- 9251453
TI  - Giant cavernous hemangiomas of liver mimicking metastasis.
AB  - Most hepatic hemangiomas are small and symptomless. These are now being
      increasingly diagnosed with the greater use of scanning procedures. Hemangiomas
      can occasionally grow to a large size and become manifest to the patient and the
      clinician. Giant hemangiomas can produce symptoms including awareness of
      abdominal mass, pain due to thrombosis, and very rarely, rupture. Though
      ultrasound is known to be quite suggestive of the diagnosis, large hemangiomas
      may be mistaken for liver metastases due to their enormous size and variegated
      picture on the scanning procedure. Dynamic CT scan and at times MRI may be
      required for confirmation of the diagnosis. Needle biopsy is contraindicated if
      the diagnosis is suspected.

PMID- 9251455
TI  - Coagulation abnormalities in non-cirrhotic portal fibrosis and extra hepatic
      portal vein obstruction.

PMID- 9251454
TI  - Cefuroxime axetil in the treatment of Salmonella typhi infection (enteric fever)
      in adults.
AB  - A study to evaluate the efficacy and safety of Cefuroxime Axetil in enteric fever
      was carried out in 30 adult hospitalised patients of either sex. A positive blood
      culture for S. typhi and sensitivity to cefuroxime axetil were confirmed prior to
      treatment. On admission, the baseline signs and symptoms were recorded and
      treatment initiated with cefuroxime axetil in a dose of 500 mg bd; which was
      continued for 7 days after normalization of temperature. The various clinical
      parameters were followed up daily during the treatment period and discharge
      permitted on normalization of temperature. Blood culture for S. typhi was
      repeated 3 days after stopping treatment. Follow-up Widal, stool and urine
      cultures were done wherever possible to check for relapse or carrier state. All
      the patients responded clinically to treatment and had bacteriologically negative
      blood cultures by the end of 14 days treatment. 87% of the patients responded
      within 7 days of treatment of which 60% were graded as Excellent responders as
      they responded within 4 days itself; while 13% took a longer time to respond.
      There were no relapses or carrier state as indicated by negative follow-up stool
      cultures. Only one patient reported a side-effect of mild headache confirming the
      safety of the drug. We conclude that Cefuroxime axetil in a dose of 500 mg bd is
      an effective and safe drug in the treatment of multi drug resistant enteric
      fever.

PMID- 9251456
TI  - Magnetic resonance angiography.
AB  - The field of MRA has progressed to a stage at which several clinical applications
      are of obvious value, including the diagnosis of cerebral aneurysms, venous
      disorders and disease of the carotid bifurcation. Additionally spin echo images
      are useful in studying the parenchyma and this together with MRA works to be an
      excellent diagnostic package in the presurgical workup of patients with cerebral
      vascular abnormalities. With further technical improvements, it seems likely that
      important applications of MRA will also be found in the diagnosis of peripheral
      artery disease, stenosis of the renal artery and ischemic heart disease. With the
      advent of fast imaging techniques like echoplanar imaging, the ability image the
      coronary and renal arteries accurately seems possible in the near future. At
      present, however the lack of optimal spatial resolution and the presence of flow
      artifacts precludes the use of this technique for imaging the vasculature with an
      accuracy comparable with conventional angiography. The advent for contrast 3-D CT
      angiography has resulted in a technique of studying the intracranial vessels
      immediately after assessing for the presence of subarachnoid hemorrhage. It is
      superior to MRA in demonstrating the actively filling and thrombused portions of
      giant, partially thrombused aneurysms and in planning the surgical approach in
      relation to bony landmarks. Though there are daunting obstacles, with continuous
      ongoing clinical research and the added inputs from a dramatically changing
      computer technology, MRA is all set to be an imaging study of great promise that
      may eventually replace diagnostic catheter angiography in most clinical
      situations.

PMID- 9251457
TI  - Urinary tract infections--a fresh look.

PMID- 9251458
TI  - HIV and the heart.

PMID- 9251459
TI  - Pneumomediastinum in association with pulmonary tuberculosis.

PMID- 9251460
TI  - Two rare parasites of the human brain--Gnathostoma spinigerum and sparganum
      (Spirometra).

PMID- 9251461
TI  - Spontaneous pneumomediastinum: cause and consequence.

PMID- 9251462
TI  - Multiple myeloma presenting as recurrent stroke.

PMID- 9251463
TI  - Bilateral basal ganglia haemorrhage--uncommon manifestation of methanol
      poisoning.

PMID- 9251464
TI  - D.C. cardioversion and pregnancy.

PMID- 9251465
TI  - Autoimmune thyroiditis--an unusual course.

PMID- 9251466
TI  - Toxoplasma encephalitis in AIDS.

PMID- 9251467
TI  - A novel exit of Taenia saginata.

PMID- 9251468
TI  - Cushings syndrome due to a pancreatic islet cell tumour.

PMID- 9251469
TI  - Pulmonary microlithiasis.

PMID- 9251470
TI  - Serial blood phosphine levels in aluminium phosphide [ALP] poisoning.

PMID- 9251472
TI  - Two hundred false Widal positive cases from eastern U.P.

PMID- 9251473
TI  - An improved simple method of detection of Bence Jones proteinuria.

PMID- 9251475
TI  - Audiovisual aids: guidelines for the use of overhead projector.

PMID- 9251474
TI  - Acute inflammatory demyelinating polyradiculoneuropathy following antirabies
      vaccine.

PMID- 9251476
TI  - Cobb syndrome.

PMID- 9251477
TI  - [Early repair of ventricular septal rupture in patients over 80 years of age:
      infarction exclusion technique].
AB  - Since 1994, three patients more than 80 years of age underwent early repair of
      ventricular septal rupture complicating acute myocardial infarction at our
      hospital. The infarction exclusion technique introduced by David and Komeda was
      employed. Average aortic clamp time, cardiopulmonary bypass time and operation
      time were 83 minutes, 129 minutes and 228 minutes, respectively. No hemostatic
      suture were required to the left ventricular suture line. All patients survived.
      One patient with posterior ventricular septal rupture had residual shunt and
      necessitated transient hemodialysis but recovered. Thus, the infarction exclusion
      technique seems to be useful in the elderly with unfavorable tissue fragility.

PMID- 9251478
TI  - [Emergency coronary artery bypass grafting in elderly patients].
AB  - Emergency coronary artery bypass grafting (CABG) in elderly patients still
      remains to be a therapeutic challenge for cardiac surgeons. The purpose of this
      study was to review the operative results of our emergency CABG in elderly
      patients and evaluate it's problems comparing with younger patients. Consecutive
      forty-three patients underwent emergency CABG for the past ten years were divided
      into two groups, that is 13 patients aged 75 years or older (group 1) and 30
      younger than 75 years old (group 2). There were three in-hospital deaths
      (mortality rate: 23.1%) in group 1 and three (10.0%) in group 2. The lowest
      postoperative Ccr (19.1 +/- 8.9 ml/ min) in group 1 was significantly lower (p <
      0.02) than that (35.6 +/- 14.4 ml/min) in group 2. Respiratory Index on the first
      postoperative day, which indicates lung dysfunction when it comes up to 2.0 or
      more, showed 2.65 in mean value in group 1 compared with 1.31 in group 2 (p <
      0.05). Severe infections like sepsis were developed in 4 patients (30.8%) in
      group 1 and 2 (6.7%) in group 2 (p < 0.05). In conclusion, it was clearly
      suggested that kidney protection by earlier myocardial revascularization,
      prevention of severe infection and earlier introduction of respiratory
      physiotherapy in the postoperative period were advisable to improve the operative
      results of emergency CABG in elderly patients.

PMID- 9251479
TI  - [Assessment of quality of life in long-term results of patients over 75 years old
      after emergent cardiovascular surgery].
AB  - Long-term results in QOL of patients over 75 years old after emergent
      cardiovascular surgery were examined. From January 1991 to June 1996, 46 patients
      underwent cardiovascular surgery. 22 patients who had elective surgery (elective
      group) and 15 patients who had emergency surgery (emergency group) tolerated with
      the operation: Two-year survival rate after surgery was 80.7% in the elective
      group and 78% in the emergency group, and relative survival rate was 0.89 in the
      elective group and 0.86 in the emergency group. As regards to the ability to live
      independently, 89% of elective group and 75% of emergency group showed good
      improvement, and there was no significant difference between two groups. The rate
      of patients who did not feel anxiety for disease at all was 61.1% in the elective
      group and 41.7% in the emergency group. The relationship between the patient and
      his family was good in both groups. For physical condition, the emergency group
      was superior to the elective group with no significant difference. Although QOL
      was relatively good after emergency surgery, some items were inferior compared
      with elective surgery. To improve the long-term results, elective surgery is
      required to avoid emergency surgery.

PMID- 9251480
TI  - [Surgical treatment of thoracic aorta for elderly patient].
AB  - From 1986 to 1996, 237 patients underwent surgical treatment of thoracic aorta in
      our institute. We classified them as follows: group 1 is 41 patients older than
      75: group 2 is 196 patients younger than 74. The number of patients of elective
      surgery, emergent surgery for acute dissection type A and emergent surgery for
      rupture or impending rupture were 28, 9, 4 in group 1 and 123, 47, 26 in group 2.
      Operative death (within 30 days) of elective surgery, emergent surgery for acute
      dissection type A and emergent surgery for rupture or impending rupture were 1
      (3.6%, MOF), 1 (11%, liver failure), 2 (50%, brain damage) in group 1 and 8
      (6.5), 3 (6.4%), 9 (35%) in group 2, respectively. Hospital deaths (after 30 days
      and cannot discharge) were 3 (11%), 0.1 (25%) in group 1 and 3 (2.4%), 1 (2.1%),
      1 (3.8%) in group 2. There was no significant difference between two groups.
      Survival rate of each group were 48% and 80% for five-year survival rate.
      Complications in elderly patients were common (88%). Respiratory insufficiency is
      the most frequent (51%). Otherwise survival rate of patients who had no surgical
      treatment of diseased thoracic aorta was reported poor by several researches. We
      will perform operation for elderly patients positively if we can get agreement of
      patients.

PMID- 9251481
TI  - [The surgical results of aged thoracic aortic aneurysm].
AB  - Eighty-five patients with thoracic aortic aneurysm (TAA) (36 dissection, 49 non
      dissection) underwent surgical intervention in our service from December 1985 to
      March 1997. 31 patients aged over 70 (aTAA) were compared with 54 patients under
      69 years of age (non-aTAA) about preoperative condition, surgical invasion, and
      operative morbidity and mortality. No significant differences were observed in
      preoperative associated condition and laboratory data between two groups except
      more non-dissection were included in aTAA (74.2%) than non-aTAA (48.1%). There
      were no significant differences in intraoperative variables and endotracheal
      intubation time and ICU staying time were shorter in aTAA (not significant). No
      significant differences were revealed in operative morbidity, mortality and five
      year actual survival rate between two groups. 16.1% of early mortality and 9.7%
      of hospital mortality for operated aTAA were acceptable, which let us conclude
      that aTAA must be operated positively before rupture by careful selection
      considering life expectancy, evaluation of risk factors or reserved physiological
      status, and surgical invasion.

PMID- 9251482
TI  - [A clinical investigation of Bentall's operation for annuloaortic ectasia in the
      elderly].
AB  - Although Bentall's operation has become a routine procedure for annuloaortic
      ectasia (AAE), few reports on its effects on operative mortality in elderly
      patients have been published. The results of Bentall's operation for AAE on 4
      elderly patients were reviewed. There were two males and two females in the
      series. The ages ranged 71 to 77 years with an average of 73. The etiology of
      aneurysms was syphilitic in three and arteriosclerotic in one patients. All
      patients had AAE, aortic regurgitation and ascending aortic aneurysms. Of all
      these patients, 1 had a subacute Type A dissecting aneurysm, 1 had a proximal
      arch aneurysm and 1 had an aortic arch aneurysm plus a sacciform descending
      aortic aneurysm. All patients had composite graft replacement with coronary
      reimplantation. Three patients received the concomitant operative procedures
      including aortic arch replacement and CABG to right coronary artery with
      saphenous vein graft. All patients survived operation. Postoperative CTR and NYHA
      classification showed remarkable improvement and serious complications were not
      found in spite of old age. In the late postoperative period, all patients were
      alive and well from 4 to 6 years after operation. Bentall's operation can be
      performed in elderly patients with AAE.

PMID- 9251483
TI  - [Aortic arch surgery in the elderly].
AB  - A consecutive series of 16 patients over 75 years old who underwent aortic arch
      operations with hypothermic selective cerebral perfusion from 1994 to 1997 was
      analyzed. These patients (group O) was compared with 18 patients aged from 70 to
      74-year-old (group M) and 38 patients under the age of 69 (group Y) who underwent
      aortic arch operation during the same period. There were 5 males and 11 females
      with a mean age of 77.8 years (range 75 to 86) in group O. Twelve patients were
      in aortic dissection and 4 patients were in atherosclerotic aneurysms. There were
      5 hospital deaths (31.2%) in group O, 2 (11.1%) in group M and 2 (5.3%) in group
      Y. There was significant difference in hospital mortality rate between group O
      and group Y. Cerebral complication occurred in 2 patients (12.5%) and
      postoperative respiratory failure occurred in 7 (47%) in group O. Aortic arch
      operations for the elderly patients can be performed with increased but operative
      mortality in the elderly patients remains high. In this study, we discussed that
      influence of risk factors on the operative result and operative indication in the
      elderly patients.

PMID- 9251484
TI  - [Surgical treatment of aortic dissection (Stanford type A) using hypothermic
      retrograde cerebral perfusion in patients older than 70 years of age].
AB  - Since 1991, 27 consecutive patients with aortic dissection (Stanford A) have been
      operated on using deep hypothermic retrograde cerebral perfusion (RCP). There
      were no differences in ECC time (247 +/- 15 vs 307 +/- 22 min), and RCP time (47
      +/- 2 vs 47 +/- 3 min) between the aged (> or = 70 y.o., n = 11) and non-aged (<
      70 y.o., n = 16) group. Although the aged group showed the higher incidences of
      postoperative neurological complications of prolonged emergence (2 cases) and
      delirium (3 cases), respiratory disorder (3 cases), and renal dysfunction (3
      cases), there was no significant difference in hospital mortality (18% in the
      aged vs 13% in the non-aged). We concluded that RCP is well acceptable procedure
      for surgical treatment of the aged patients with aortic dissection.

PMID- 9251485
TI  - [Heart valvular disease in patients 70 years old and older].
AB  - From June 1986 to December 1996, 69 patients older than 70 years old underwent
      AVR (29 cases), MVR (21 cases), MVP (5 cases), DVR (10 cases), aortic root
      replacement (3 cases), repair of PVL (1 case) in our hospital. There are five
      (7.2%) operative and hospital deaths. The survival rate was 88.4% at 10 year
      after surgery and three (4.7%) late deaths. The factors associated with early
      deaths were renal dysfunction and DVR. Our surgical results suggest that open
      heart surgery can be performed safely even elderly patients, in spite of their
      precarious physiologic homeostasis. Not the chronological age but the
      physiological age is important determinant for surgical indication. If quality of
      life (QOL) can be expected to be enhanced, we recommend an aggressive surgical
      approach.

PMID- 9251486
TI  - [Mitral valve re-replacement in patients aged 70 years and older: is age alone
      not operative risk factor?].
AB  - We analyzed the risk of mitral valve re-replacement (re-MVR) in patients over 70
      year-old. Surgical and late follow-up results were compared between 14 elderly
      patients over 70-year-old (group I) and 23 patients aged from 60 to 69-year-old
      (group II) who underwent re-MVR due to primary tissue failure (PTF). Donation of
      autologous blood and a rate of replaced valve prosthesis (mechanical/biological)
      were different between the two groups. There were no differences in the other
      factors such as clinical profile, preoperative organ function, operative
      characteristics, post operative relating factors. No operative death occurred in
      both groups. There was one hospital death in group I (a hospital mortality rate
      of 7.1%). The cause of death was related to massive cerebral infarction due to
      anticoagulant-related thromboembolic event. 4-64 months after re-MVR, the
      improvement of a NYHA function class was I-II in the two groups. With improvement
      in myocardial protection and intraoperative strategies, the operative risk in
      patients undergoing re-MVR over 70-year-old has been markedly reduced. Surgical
      results in aged patients were satisfactory and age alone is not a
      contraindication for this operation. The re-MVR in aged patients should be done
      at the early stage of PTF before progress of cardiac failure.

PMID- 9251487
TI  - [Coronary artery bypass grafting in patients aged 80 years or older].
AB  - Coronary artery bypass grafting (CABG) in elderly patients was increasing in
      recent years. Between January 1989, and December 1996, 11 patients aged 80 years
      or older (mean 81) underwent CABG in our hospital. Nine patients (82%) were in
      New York Heart Association class III or IV. Emergency surgery was required in 4
      patients (36%). Incidence of emergency surgery is higher than younger patients (p
      < 0.005), emergency surgery required 7.7% (46/592) in younger patients. The
      operative mortality was 27% for these 80 years or older. It was one in elective
      cases and two of four (50%) in emergency cases. One operative death in elective
      cases was concomitant operation with arch aneurysm. More patients of CABG
      operations in octogenarians required emergency surgery, and emergency surgery is
      high operative mortality. Thus CABG in octogenarians should be performed earlier,
      not be denied because of age alone.

PMID- 9251488
TI  - [Surgical results of coronary artery bypass grafting in patients older than 75
      years].
AB  - We studied 19 patients, all older than 75 years of age, who had isolated coronary
      artery bypass grafting (CABG) from January 1990 to December 1996. Clinical
      characteristics, hospital mortality and long-term survival were compared between
      this elderly group (> or = 75 years) and a younger group (60-74 years) in which
      130 consecutive patients underwent the same procedure during the same period.
      There were no differences of coronary risk factors, renal function, respiratory
      function and ejection fraction between the two groups. The incidences of left
      main trunk stenosis (> or = 50%) and three-vessel-disease were more common in the
      elderly group, but the difference between the groups was not statistically
      significant. Preoperative use of an intra-aortic balloon pump was more frequent
      in the elderly group (p < 0.01). The hospital mortality rate of 31.6% for the
      elderly group was significantly higher than that of 5.4% for the younger group (p
      < 0.01). However, of particular note is that the 30-day hospital mortality was
      half (15.8%) and that three of six (50%) hospital deaths occurred between 35 and
      148 days. These patients died from acute respiratory failure subsequent to
      aspiration pneumonia, ruptured dissecting aortic aneurysm, and ischemic
      enterocolitis. This difference between the 30-day hospital mortality rate (15.8%)
      and hospital mortality rate (31.6%) emphasizes the influence that postoperative
      complications can have on subsequent outcome. Of 136 hospital survivors (123 in
      the younger group and 13 in the elderly), 98% have been followed for a mean of 32
      months. The 4-year survival was 60 +/- 22% for hospital survivors of the elderly
      group. It compares favorably with that for the younger group (85 +/- 5%), and
      with previously reported data. We conclude that despite a significantly increased
      hospital mortality, good long-term survival can be realized after CABG, even in
      patients older than 75 years.

PMID- 9251490
TI  - [Coronary artery bypass grafting with arterial grafts in the elderly patients].
AB  - One hundred six consecutive patients aged 75 years and over (mean age 77.1, 75
      84) underwent coronary artery bypass. Controlled group is 287 patients undergoing
      CABG in 1996. The number of bypass graft, arterial graft, Ao-cross clamp time,
      CPB time, operation time in aged group and controlled group were as follows 3.3
      and 3.3, 1.9 and 2.5 (p < 0.01), 106 and 104, 333 and 328. The number of
      anastomose per patients with LITA, SVG, GEA, RITA, IEA, RA, as follows 1.0 and
      1.0, 1.5 and 0.5, 0.6 and 0.5, 0.1 and 0.14, 0.03 and 0.03, 0.2 and 3.3 SVG were
      used significantly high and RA were used low in aged group. Sequential bypass
      were under went 30.1% in aged group and 35.5% in controlled group. There was no
      operative death in elective operation, 5 (4.9%) was died in emergent operation. A
      favorable outcome may be expected when coronary bypass surgery with arterial
      graft is performed in 75 years and over aged group.

PMID- 9251489
TI  - [Coronary artery bypass surgery in patients aged 75 years and older].
AB  - Coronary artery bypass grafting (CABG) has been performed for elderly patients
      with increasing frequency. Several studies have shown that the rate of
      complications and mortality in elderly patients are higher than in younger ones.
      This report presents results of CABG in patients over 75 years old. From January
      1989 to February 1997, 604 patients underwent CABG, of whom 20 patients (3.3%)
      were 80-86 years old (group A) and 57 patients (9.4%) were 75-79 years old (group
      B). We compared these two groups with 100 younger patients (group C).
      Preoperative use of intraaortic balloon pumping and the emergency operation were
      more frequent in patients of group A (emergency 45%, IABP 20%). And the
      proportion of the no blood transfusion procedures was lower in elderly patients
      (group A 20%, group B 18%, group C 82%). The number of grafts per patient (group
      A 2.45 +/- 0.62, group B 2.2 +/- 0.6, group C 3.2 +/- 0.6) and the number of
      arterial grafts (group A 1.25 +/- 0.62, group B 1.25 +/- 0.66, group C 2.1 +/-
      0.53) were different between the groups. But CABG in elderly patients was
      performed with low hospital mortality (group A 0%, group B 0.18%) and significant
      symptomatic benefit. We conclude that CABG can be performed in elderly patients
      with acceptable mortality and acceptable quality of life, so patients should not
      denied operation because of an advanced age.

PMID- 9251491
TI  - [Coronary artery bypass surgery in patients over 75 years].
AB  - Coronary artery bypass graft surgery is increasingly common in patients over 75
      years. In our institution, a consecutive series of 936 patients undergoing
      isolated CABG between May 1988 and July 1996 included 154 patients older than 75
      years. These elderly patients were divided into two group (group A: 40 patients
      over 80 years old, group B: 114 patients younger than 80 years) and the patients
      in group A and group B were compared with 100 consecutive patients younger than
      75 years who underwent CABG in 1996 (group C). Mean age for elderly patients was
      78.1 and for group C patients 64.2 years. Emergency operation and preoperative
      use of IABP were significantly frequent in group A (p < 0.05). Left main trunk
      stenosis was more frequent in group A patients (p < 0.05), while the number of
      diseased vessels did not differ. Mean number of grafts and arterial grafts were
      higher for group C patients. The frequency of use of arterial grafts in elective
      cases were lower for group A and group B patients. (p < 0.05, 86.3% group A,
      91.3% group B, 100% group C). Although the frequency of mediastinitis and long
      stay of ICU (over 5 days) were significantly higher in group A (p < 0.05) and
      older patients tended to have higher postoperative morbidity, the hospital
      mortality did not differ between the groups (5.0% group A, 4.4% group B, 1.0%
      group C). We conclude that CABG in patients over 75 years of age can be performed
      with acceptable mortality. Patients should not be denied CABG because of age
      alone.

PMID- 9251492
TI  - [Coronary bypass surgery in the elderly: characteristics and quality of life].
AB  - From November 1991 to December 1996, 66 patients aged 70 years or more underwent
      coronary artery bypass grafting (CABG). They were compared with a group of 200
      consecutive patients aged less than 70 years of age who underwent CABG during the
      same period. The elderly patients had a higher incidence of female gender,
      smaller body structure, left main trunk disease, calcification of ascending aorta
      and emergency operation. However, there were no significant differences between
      two groups in hospital mortality, IABP insertion or length of stay in intensive
      care unit. Quality of life (QOL) of the elderly patients was evaluated for all
      the 58 survivors by means of Specific Activity Scale Questionnaires. Forty of the
      58 patients (69%) had functional capacity of 5 METs or more. All the 43 patients
      who worked before CABG were able return to work, although some patients reduced
      their workload. We conclude that CABG in elderly patients can be performed with
      mortality and morbidity similar to those in younger patients. QOL is generally
      maintained.

PMID- 9251493
TI  - [Coronary artery bypass grafting in patients over 70 years old].
AB  - We examined the outcome of CABG in 157 patients aged over 70 years. The average
      age was 72.7 +/- 2.4 years: the number of the diseased vessels, 2.5 +/- 0.7/pt;
      the mean preoperative LVEF, 0.55 +/- 0.17 and the number of patients with left
      main trunk disease, 40 (26%). The mean number of bypass grafts was 2.8 +/-
      0.8/pt. In 131 patients (83.4), left internal thoracic artery (LITA) was used to
      bypass the left anterior descending artery (LAD). The postoperative hospital
      mortality rate was 6.4%. After 10 years of follow-up, the actuarial survival rate
      and cardiac event-free rate were 73.6% and 88.9%, respectively calculated by the
      Kaplan-Meier method. A comparison of the long-term results of CABG with and
      without ITA grafting, showed no statistical difference with respect to actuarial
      survival rate. However, the cardiac event-free rate was improved by using an ITA
      graft (92.4% with an ITA vs 77.3% without an ITA, p = 0.047). This result
      suggested that the use of ITA in patients over 70 years old reduced the incidence
      of postoperative cardiac events without increasing the operative risk.

PMID- 9251494
TI  - [Coronary artery bypass surgery in aged patients].
AB  - From January 1993 through December 1996, 749 patients underwent isolated coronary
      artery bypass grafting. Of these patients, 578 patients were older than 60 years
      old. We classified them into three groups; Group A were the 60 to 69 year age
      group (337 patients), Group B were the 70 to 79 year age group (224 patients) and
      Group C were over 80 years age group (17 patients). Emergency cases and
      preoperative LV dysfunction cases were more frequently in Group C, but mortality
      did not differ among three groups. Duration of intubation, ICU stay and hospital
      stay were longer in Group C than other groups and complications (PMI, arrhythmia
      and reoperation for bleeding) were more frequently in Group C. Coronary artery
      bypass surgery can be performed in aged patients, especially for patients over 80
      years old, with acceptably low mortality and significant functional benefit but a
      high incidence of complications necessitates careful postoperative management in
      aged patients.

PMID- 9251495
TI  - [Coronary artery bypass surgery in patients older than 70 years of age].
AB  - From April 1994 to November 1996, coronary artery bypass grafting (CABG) was
      performed on 166 patients. Fifty-seven patients were older than 70 years of age
      (Group A), while 109 were younger than 70 years of age (Group B). In group A,
      such symptoms as severe stenosis of the left main coronary artery, a history of
      systemic hypertension, calcification of the ascending aorta, and postoperative
      respiratory complications with pneumonia were all significantly higher than in
      Group B. Regarding hospital mortality, the difference between the two groups was
      not significant. Based on these findings, the use of intensive respiratory care
      for elderly patients over than 70 years of age is thus considered to help reduce
      the occurrence of such complications.

PMID- 9251496
TI  - [Coronary artery surgery in elderly patients].
AB  - We have experienced 351 cases of coronary artery bypass grafting in patients 70
      years of age or older (107 cases: 75 years of age or older, 26 cases:
      octogenarians), among 1,395 cases of all coronary artery bypass grafting surgery.
      Estimated hospital death rate 4.8% seemed to be satisfactory.

PMID- 9251497
TI  - [Postoperative electroencephalographic change in old patients with cardiac
      surgery].
AB  - The purpose of this study was to evaluate cerebral dysfunction in aged patients
      associated with cardiac surgery using quantitative electroencephalograph (QEEG).
      Seventeen consecutive patients undergoing cardiac surgery were investigated.
      There were nine males and eight females whose ages ranged from 65 to 77 years
      (mean 70.6 years). The cardiac procedures consisted primarily of coronary artery
      bypass (eleven patients) and valve replacement (six patients). They had good
      postoperative course, no complications were recognized. Each patient had an EEG
      examination using digital EEG equipment in first day before operation. Follow up
      investigations were repeated three times (first day, fifth day and one month
      after operation). QEEG analysis consisted of fast Fourier transform method was
      performed in each record. A fall in the peak frequency at basic rhythm was seen
      in 1st and 5th postoperative day. A power spectra corresponding to slow wave
      showed an increase at parieto-occipital area in 1st and 5th postoperative day.
      Alpha activity at occipital area was increased in one month after operation. The
      EEG change in first or fifth postoperative day suggested the patients had
      cerebral dysfunction without clinical findings.

PMID- 9251498
TI  - [Open heart surgery without homologous blood transfusion in elderly patients].
AB  - Preoperative autologous blood donation has been widely accepted to perform
      surgery in orthopedics, gynecology and cardiac surgery. In elderly patients,
      however, it has been supposed that most of these patients have anemic tendency
      before predonation as well as poor response to erythropoietic stimuli, so that
      preoperative blood deposit is limited to apply them. In order to reduce
      homologous blood transfusion in open-heart surgery, preoperative blood deposit,
      combined with erythropoietin administration and intraoperative blood salvage,
      have been routinely used even for the elderly patients in our hospital since
      1989. In present study, we verified above concepts and obtained the results that
      demonstrated little differences in the blood reproducing ability, the rate of
      predonation, and the recovery after the operation, between the elderly and the
      younger. We concluded that autologous blood transfusion combining preoperative
      deposit with intraoperative blood salvage was the efficient and safe method even
      in the elderly patients.

PMID- 9251499
TI  - [Combined erythropoietin and aprotinin use for blood conservation in elderly
      coronary bypass patients].
AB  - Age is one of the predictors of homologous blood transfusion (HBT) in cardiac
      surgery. To avoid HBT, we have employed pharmacological blood conservation
      techniques such as the administration of erythropoietin (EPO) in conjunction with
      autologous blood donation (ABD) and the administration of aprotinin in prime
      volume. The effectiveness of these methods was evaluted in elderly patients who
      underwent coronary artery bypass grafting (CABG). Seventy-nine elective coronary
      bypass patients were classified into two groups by age: group A (> or = 70 y.o.,
      n = 29) and group B (< 70 y.o., n = 46). EPO (24,000 U) was administered once a
      week subcutaneously starting 3 weeks before the operation. ABDs were carried out
      as long as the blood hemoglobin levels were above 10.5 g/dl. A significant
      increase of preoperative blood hemoglobin was observed in both groups. Although
      the blood hemoglobin levels at the beginning of ABD were lower in group A than in
      group B, the mean amount of predonated blood per patients was similar in both
      groups. In 79.3% of group A and in 84.8% of group B, HBT was not required:
      furthermore, in the prodonated patients, this no-HBT rate could be increased to
      84.0% of group A and to 88.1% of group B. These results suggest that CABG in
      elderly patients can be performed safely without HBT when pharmacological blood
      conservation techniques are employed.

PMID- 9251500
TI  - [Cardiac operation for aged patients (aged 75 years and over): results of
      surgical intervention].
AB  - We evaluate the results of cardiac operation for 41 elderly patients (aged 75
      years and over, mean, 77.5 years old). The overall hospital mortality was 12.2%
      (5/41) with mortality of 8.3% (2/24) in cases of elective operation and mortality
      of 17.6% (3/17) in cases of emergency operation. Causes of hospital death in
      emergency cases were congestive heart failure and left ventricular rupture (two
      cases) due to acute myocardial infarction. Patients who died in elective
      operation had been performed reoperation for bleeding and unstable sternum. These
      complications which need a reoperation seemed to be a potential risk for elderly
      patients. Because of poorer results of the emergency case, it is advocate to
      operate on these aged patients with an elective basis, if there is no absolute
      contraindications.

PMID- 9251501
TI  - [Results of cardiac operation and thoracic aortic operation in patients aged 75
      years or older].
AB  - A total of 121 patients aged 75 years or older underwent cardiac operation or
      thoracic aortic operation at our hospital between 1988 and February 1997. They
      were composed of 74 cases of ischemic heart disease, 22 cases of valvular
      disease, 1 case of myxoma, and 24 cases of thoracic aortic disease. Operative
      mortality rate was 13.5% in ischemic heart disease, 4.2% in valvular disease and
      myxoma, and 25% in thoracic aortic disease. In ischemic heart disease, the
      operative mortality rate was especially high in emergency operation for acute
      myocardial infarction. In thoracic aortic operation, further improvement should
      be made with regard to preoperative and intraoperative management.

PMID- 9251502
TI  - [Early and late results of cardiac and thoracic aortic surgery in patients older
      than 75 years from a quality of life point of view].
AB  - To determine the early and late results of cardiovascular surgery in patients
      older than 75 years old, we performed a retrospective study of 28 consecutive
      elderly patients between January, 1987 and July, 1996. Fourteen patients had
      cardiac surgery, and 14 had thoracic aortic surgery. Among all of them, nine
      patients had an emergency operation. The follow-up time ranged 7 to 76 months
      (mean 20.7 +/- 25.0). The total follow-up time was 561 patients months. The
      hospital mortality rate was 32.1% (9/28) over all and 15.8% (3/19) for the
      elective procedures. The early result during the latter five years decreases more
      than during the early five years (55% vs. 18%, respectively). Three patients died
      during the follow-up period. One patient dropped out of the follow-up. All 15
      survivors were satisfied with their quality of life. Among the survivors of
      cardiac surgery, the mean New York Heart Association functional classification
      score decreased significantly (preoperative 3.0 +/- 0.89, follow-up 1.5 +/-
      0.55). Though the early mortality is unsatisfactory, it is improving. This follow
      up study demonstrates the benefits of cardiovascular surgery in elderly patients
      in terms of social integration and quality of life.

PMID- 9251505
TI  - [Effect of controlled hypotension on cerebral oxygen delivery].
AB  - The margin of safety for controlled hypotension is still unclear especially in
      the central nervous system (CNS) which is one of the most sensitive organs to
      hypoxia and ischemia. Recently, cerebral optical spectroscopy in the infrared
      light range was developed as a useful tool which makes it possible to monitor
      cerebral oxygenation (rSO2) non-invasively and continuously during anesthesia.
      Resulting rSO2 mainly reflects oxygen extracts by cerebral tissue and then
      indicates cerebral oxygen delivery. We examined the limitation of controlled
      hypotension in the brain in 12 patients by monitoring rSO2 during anesthesia.
      rSO2 under room air breathing (control value as normal physiological condition)
      was 67 +/- 3% (mean +/- SEM). It significantly increased by 5.6 +/- 0.8% under
      100% oxygen breathing, but decreased near to the control value under sevoflurane
      anesthesia (FIO2 1.0). During moderate controlled hypotension (70% of normal
      blood pressure) by prostaglandin E1 under sevoflurane anesthesia (FIO2 1.0). rSO2
      remained at control value, indicating that cerebral oxygen delivery was still
      sufficiently maintained. However rSO2 decreased significantly by 9.0 +/- 1.1% in
      same controlled hypotension condition under FIO2 0.4. This decrease in rSO2 could
      be potentially harmful for CNS although any post-operative neurological disorder
      was not observed in our cases. We conclude that cerebral oxygen delivery may be
      insufficient even in the moderate controlled hypotension, and thus higher FIO2 is
      recommended in such procedures.

PMID- 9251504
TI  - [Effects of toborinone on systemic circulation in patients under general
      anesthesia].
AB  - Patients with suppressed systemic circulation under general anesthesia received a
      20-minute continuous infusion of toborinone at a rate of 5, 10, or 15
      micrograms.kg-1.min-1, and the efficacy and safety of the drug were evaluated.
      Toborinone increased cardiac index (CI) and stroke volume index (SVI) dose
      dependently, with significant increases at 10 and 15 micrograms.kg-1.min-1. An
      increase in CI was observed from 10 minutes after the start of infusion, with a
      return to the baseline value at 20-30 minutes after the completion of infusion.
      Toborinone did not affect heart rate at any dose tested, but the drug tended to
      decrease mean pulmonary arterial pressure, pulmonary capillary wedge pressure,
      and right atrial pressure. Mean arterial blood pressure tended to decrease after
      the start of infusion at all doses tested, and was significantly decreased at 20
      minutes after the start of infusion at 10 and 15 micrograms.kg-1.min-1. Systemic
      vascular resistance and pulmonary vascular resistance decreased at all doses
      tested. T-wave amplitude on electrocardiaogram (ECG) and oxygen partial pressure
      in arterial blood decreased at 10 and 15 micrograms.kg-1.min-1. Toborinone
      increases cardiac output and decreases pre-load and after-load with no effects on
      heart rate, and, therefore, is thought to be a positive inotropic agent useful in
      the treatment of circulatory insufficiency. Due care should be exercised to
      monitor blood pressure, ECG, and arterial blood gas parameters of the patients.
      The effects of toborinone need to be further investigated in patients with
      complicated cardiac diseases under general anesthesia and in patients with
      circulatory insufficiency after surgery, including patients following
      extracorporeal circulation.

PMID- 9251506
TI  - [The comparison of IRV and PEEP on gas exchanges in dogs with aspiration
      pneumonia].
AB  - The purpose of this study was to determine the effects of pressure control
      inverse ratio ventilation (PC-IRV) and PEEP (in which both mean airway pressure
      and tidal volume were the same), on the gas exchange and the hemodynamics in 40
      dogs in which the bronchi were injected with 2 ml.kg-1 0.1 N-hydrochloric acid.
      The dogs were classified into 5 groups and were ventilated with 5 kinds of
      ventilatory modes for 8 hours. The control group was ventilated by volume control
      ventilation (VCV) without PEEP, using a Servo Ventilator 900 C. Group A was
      ventilated artificially by VCV with 5 cm H2O PEEP for 3 hours after
      administrering hydrochloric acid; the group was then ventilated with PC-IRV for
      the next 5 hours. Group B was ventilated with the reversed ventilatory modes of
      group A. Group C was ventilated by VCV with 10 cm H2O PEEP after injecting
      hydrochloric acid, and a ventilatory mode with PC-IRV was used for the next 5
      hours. Group D received the reversed ventilatory modes of group C. In all groups,
      PaO2 decreased from about 140 to 70 mmHg by injecting hydrochloric acid. PEEP
      improved arterial oxygenation significantly depending on the PEEP level, but PC
      IRV did not improve PaO2 in the dogs in which aspiration pneumonia was induced.
      In group C, PaO2 showed the highest increase. PC-IRV decreased PaCO2. It was
      concluded that PC-IRV did not improve arterial oxygenation but showed a favorable
      effect for CO2 elimination in dogs with aspiration pneumonia induced by
      hydrochloric acid.

PMID- 9251507
TI  - [Pharmacokinetics of isosorbide dinitrate examined by physiologically-based
      pharmacokinetic model].
AB  - To make a physiologically-based pharmacokinetic model of isosorbide dinitrate
      (ISDN), the author infused ISDN at 1, 10, 30 micrograms.kg-1.min-1 into
      anesthetized rabbits and measured concentrations of ISDN and its metabolites (2
      ISMN and 5-ISMN) in plasma and in the brain, liver as well as fat tissue. There
      was the accumulation of ISDN in the brain and fat tissue. There was no
      significant difference in concentrations of ISDN between the plasma and liver, or
      in concentrations of its metabolites among plasma, and the tissues of the brain,
      liver and fat. Using these informations, the author constructed a physiologically
      based pharmacokinetic model to human and estimated values were compared with
      observed values to determine the validity of the model. There was no remarkable
      differences between the estimated values and observed values. This suggests the
      validity of the model. The plasma concentrations of ISDN estimated by this model,
      showed a linear increase (Y = 25 X) with the infusion rate less than 6.0
      micrograms.kg-1.min-1. The accumulation of ISDN, especially in the brain was
      suggested by this model.

PMID- 9251508
TI  - [Adrenergic receptor and alpha 2 agonist--2: Function analysis of adrenoceptor
      subtype by knockout mice and knockdown rats].
AB  - Alpha 2 adrenergic agonists will soon be used in the anesthetic management for
      their sedative/hypnotic, anesthetic-sparing, analgesic and sympatholytic
      properties. But the clinically available alpha 2 agonists have unwanted side
      effects such as acute hypertension and bradycardia following a bolus injection
      because these agonists do not discriminate between the 3 alpha 2 adrenoceptor
      subtypes. Molecular biological methods can identify mediating receptor subtype
      for each response. Knockout mice study reveals that the alpha 2 B adrenoceptor
      subtype mediates the hypertensive response to alpha 2 agonists. Knockdown study
      using the antisense technology demonstrates that the alpha 2 A adrenoceptor
      subtype mediates the hypnotic and analgesic effects of alpha 2 agonists. The next
      generation of alpha 2 agonists should be alpha 2 A selective to maximize
      anesthetic and analgesic effects while minimizing hypertensive response.

PMID- 9251510
TI  - [A risk of pulmonary edema associated with G-CSF pretreatment].
AB  - We reported a case of severe pulmonary edema in the normal adult after bone
      marrow harvesting (BMH), who had received granular cell stimulating factor (G
      CSF) pretreatment. The patient was 38 year old healthy man who was a donor to his
      son suffering from SCID (severe complicated immunodefficiency). He was
      administered total of G-CSF 750 mcg for three days before BMH. At the end of the
      BMH procedure, the patient was becoming dyspneic followed by severe pulmonary
      edema that continued about 8 hours. The levels of TNF alpha and IL-6 in his
      plasma and endotracheal exudate were abnormally as high as 10 and 130 pg.ml-1 of
      TNF alpha in plasma and exudate respectively and as 51.8 pg.ml-1 of IL-6 in
      plasma. We speculate that G-CSF activates white cells and induces leaking of
      cytokines from white cells, and the severity of pulmonary edema is associated
      with the cytokines.

PMID- 9251509
TI  - [Postoperative brain infarction in a patient with the previous asymptomatic brain
      infarction].
AB  - We report a case of a postoperative brain infarction, in which an asymptomatic
      preoperative brain infarction was also revealed postoperatively. A 63-year-old
      man with bladder carcinoma was scheduled for the cystoplasty. The patient had no
      prominent preoperative abnormality. Anesthesia was maintained with isoflurane in
      N2O/oxygen combined with a spinal block and a continuous epidural block.
      Anesthesia lasted uneventfully for 16.5 hours. However, emergence from anesthesia
      was delayed. On the first postoperative day, motor aphasia and right
      hemiparalysis was confirmed. The computed tomography (CT) of the brain
      demonstrated a low density area in the frontoparietal region. The magnetic
      resonance imaging (MRI) indicated the corresponding lesion as the CT had
      demonstrated, and an old brain infarction in the parietal region. This meant that
      the patient had a history of asymptomatic brain infarction (ABI). Patients with
      ABI are considered to be a high-risk group for a brain infarction. It is
      important to evaluate the risk factors of brain infarction preoperatively and to
      minimize those risks during the operation. Maintenance of the cerebral perfusion
      pressure is imperative.

PMID- 9251511
TI  - [A patient with acromegalic heart disease--a case report].
AB  - A perioperative anesthetic management of a 69 year old woman with acromegaly
      whose clinical course was characterized by severe heart failure is described. The
      patient showed symptoms of massive cardiomegaly. Endocrine studies indicated that
      her pituitary tumor was active with hyperproduction of growth hormone. There was
      no demonstrable evidence for other known causes of heart disease. Following
      hormonal therapy using continuous subcutaneous infusion of somatostatin for about
      two months, there was improvement in daily activity and reduction in heart size.
      After the improvement of cardiac function, transsphenoidal hypophysectomy was
      performed under general anesthesia and its perioperative course was quite
      uneventful. We conclude that because cardiac involvement such as left ventricular
      dilatation in acromegaly might be reversible with proper treatment, any surgical
      procedure, as long as the case is elective, should be considered after hormone
      therapy.

PMID- 9251512
TI  - [Anesthetic management of a child with Hunter syndrome associated with sleep
      apnea].
AB  - A 2-year-old boy with Hunter syndrome was scheduled for adenotomy under general
      anesthesia. Preoperative examinations of this patient revealed that he had
      stridor, sleep apnea, short neck, and a hypertrophic pharyngeal structure as
      revealed by fiberoptic pharyngoscopy, from which we expected to encounter
      difficulty in mask ventilation and tracheal intubation. On standby with settings
      for an emergency fiberoptic laryngoscopy and an emergency tracheotomy, we first
      attempted slow induction technique preserving spontaneous breathing. Thereafter
      mask ventilation was possible and a muscle relaxant was administered. On the
      second trial, almost blind orotratcheal intubation was successful.
      Postoperatively, mechanical ventilation was performed for 12 hours, in
      consideration of the airway obstruction due to pharyngeal bleeding and edema. The
      most severe anesthetic complication in the case of Hunter syndrome is the
      difficulty of intubation and respiratory disorder. Preoperative evaluation of the
      upper airway and careful perioperative monitoring and observation of respiration
      are of the greatest importance.

PMID- 9251513
TI  - [Oro-pharyngeal burn during electrodissection of the adenoid and tonsil].
AB  - We present a case of oro-pharyngeal burn which occurred during electrodissection
      of the adenoid and tonsil in a 5-year-old boy. We intubated the patient with an
      uncuffed spiral tube of appropriate size and noticed a slight gas leak during
      positive-pressure ventilation. Anesthesia was maintained with a mixture of 60%
      nitrous oxide, 40% oxygen and 2.5% sevoflurane. During manipulations of the right
      tonsil, orange-colored flame blew out about 5 cm from the mouth. Fortunately, the
      patient underwent the operative procedures without any further troubles,
      recovered fully from the grade 1 burn in the oral mucosa, and was discharged 23
      days after surgery. The surgeons speculated that sevoflurane had been ignited.
      Although it is well known that sevoflurane is nonflammable in the concentration
      of clinical use, several reports show that sevoflurane is flammable in
      concentration of 10% under pure oxygen or nitrous oxide. We concluded that this
      accident was caused by electrocautery-induced ignition of the gauze packed into
      the larynx under a high concentration of oxygen which leaked through an uncuffed
      endotracheal tube. We have to bear in mind that any flammable substance may
      ignite when using electrocautery in a small space such as the mouth under oxygen
      rich environment.

PMID- 9251515
TI  - [Hypercapnea during thoracoscopic surgery under regional anesthesia].
AB  - A 23-year-old woman was supposed to undergo thoracoscopic surgery for the 10th
      pneumothorax that accompanied histiocytosis X. The past history included Lylle's
      disease, asthma, myocarditis, drug-induced leucocytopenia and bronchitis
      obliterans. The preoperative arterial blood gas analysis under receiving O2 at
      rate of 2 l.min-1 via a nasal cannula revealed normal values. General anesthesia
      and intubation with a double-lumen endotracheal tube would have been preferable,
      but regional anesthesia was chosen because of her medical history and positive
      results of the skin tests for vecuronium, pancronium, diazepam and midazolam.
      During the first 10 min of thoracoscopic procedure, her respiration became rapid
      and shallow and she was restless and comatose. The operation was cancelled.
      Arterial blood gas analysis under receiving O2 at rate of 4 l.min-1 via a face
      mask revealed: pH 7.025, PaO2 113.8 mmHg, PaO2 244.8 mmHg, HCO3- 29.7 mEq.l-1, BE
      5.6, and O2 saturation 99.1%. Manual artificial ventilation with a mask and bag
      was initiated. Her spontaneous respiration and consciousness recovered in next 30
      min. The postoperative course was uneventful. Tachypnea, caused from anxiety,
      dyspnea and stimulation of irritant receptors in the airway, were considered to
      be responsible for the event. The duration of inspiration became shorter as
      tachypnea developed, that made the tidal volume to decrease and hypercapnea
      ensued.

PMID- 9251514
TI  - [A survival case of intraoperative pulmonary embolism diagnosed early by
      transesophageal echocardiography].
AB  - An otherwise healthy 36-year-old housewife was diagnosed with advanced cancer of
      the stomach 5 months after her third parturition. Surgery was performed with the
      patient under total intravenous anesthesia combined with continuous epidural
      anesthesia. The course of anesthesia and the operative course were uneventful
      until the abdominal skin was sutured, when unexplained severe circulatory
      collapse developed. A widely dissociated PETCO2- PaCO2 suggested pulmonary
      embolism, and the findings of transesophageal echocardiography corroborated the
      diagnosis. Infusion of 480,000 units of urokinase in 30 minutes was immediately
      started via a Swan-Ganz catheter, and intravenous heparin 10,000 units in 24
      hours, was administrated continuously. The pulmonary circulation was restored 30
      minutes after the start of therapy, resulting in rapid recovery of the patient's
      systemic circulatory and acid-base status. The patient was safely extubated 19
      hours postoperatively.

PMID- 9251516
TI  - [The effects of thoracic epidural anesthesia combined with phentolamine infusion
      in a patient with low left ventricular ejection fraction undergoing resection of
      aortic abdominal aneurysm].
AB  - The subject was a 73 year old man scheduled for resection of abdominal aortic
      aneurysm. The patient had a past history of myocardial infarction and his left
      ventricular ejection fraction was 21%. Anesthesia was maintained with thoracic
      epidural anesthesia combined with light general anesthesia using NLA technique.
      Phentolamine was infused for after-load reduction. We maintained the
      intravascular volume with infusion therapy and mild hemodilution was performed.
      As the result of these procedures, systemic vascular resistance decreased and
      cardiac index increased after the induction of anesthesia. Forrester
      classification was subset I at any point during the surgery. Hemodynamic changes
      were not significant after clamping and unclamping of the aorta. We conclude that
      successful anesthetic management of this patient was due to the epidural
      anesthesia and combined use of phentolamine as a vasodilator.

PMID- 9251517
TI  - [Delayed emergence from propofol, nitrous oxide and oxygen anesthesia--a case
      report].
AB  - We report a case of delayed recovery after the termination of propofol and
      nitrous oxide anesthesia. On the preoperative examination hepatic dysfunction
      (Indocyanine green (ICG) plasma retention rate at 15 minutes of 22%) was pointed
      out. Anesthesia was maintained with epidural block, nitrous oxide, oxygen and
      propofol. Average infusion rate of propofol was 5-6 mg.kg-1.h-1. Although at the
      end of the operation, the propofol infusion and nitrous oxide were stopped
      simultaneously, 59 minutes were necessary before the emergence from anesthesia.
      We consider that an average infusion rate of propofol should be decelerated in a
      case of ICG clearance time elongation.

PMID- 9251518
TI  - [Massive bleeding from the ruptured liver and the inferior vena cava controlled
      with autotransfusion and cerebral ischemia treated with mild hypothermia].
AB  - A patient suffered massive bleeding from the ruptured liver and laceration of the
      inferior vena cava due to traffic accident, and developed hypotension and
      decreased level of consciousness. The patient was transferred to our hospital for
      an emergency operation against intra-abdominal massive bleeding. This massive
      bleeding was controlled with autotransfusion using washing salvaging
      autotransfusion device (Cell Savor). Suspected brain ischemia was treated with
      intended mild hypothermia. When blood pressure decreased to 30 mmHg of systolic
      pressure over 7 minutes during the operation, suggesting the possible brain
      ischemia, mild hypothermia was maintained at 33.8 degrees C. Total bleeding
      volume was 16,700 ml, and total transfused volume was 10,700 ml. Of total
      transfused volume, 4,500 ml was washed salvaged blood using the intraoperative
      autotransfusion device. No neurological deficit was found during the
      postoperative course. The patient was discharged uneventfully on the 20th
      postoperative day. In conclusion, intraoperative autotransfusion with washed
      salvaged blood is a useful method for treatment of massive bleeding, and mild
      hypothermia is efficacious for protecting the brain from ischemia resulting from
      accidental hypotension.

PMID- 9251519
TI  - [Intraoperative re-rupture of gastric varix immediately after the start of an
      operation in a patient with liver cirrhosis].
AB  - Gastroesophageal variceal hemorrhage is a rare complication during an operation.
      We present a case of gastric variceal re-rupture during an emergent operation for
      devascularization of the gastric veins. The patient was a 72-year old man with
      liver cirrhosis, who developed gastric variceal hemorrhage on the day of surgery.
      Sclerotherapy with an endoscope was performed, and the hemorrhage was controlled
      four hours before entering the operating theater. The induction of anesthesia and
      tracheal intubation were done with rapid sequence because the patient was
      regarded as full stomach. Induction was completed successfully. However, gastric
      varix ruptured immediately after the beginning of the surgery. The hemorrhage
      into the stomach amounted to 2,165 ml. The patient developed hypotension of 40
      mmHg of systolic pressure for 15 minutes. With fluid resuscitation, continuous
      infusion of dopamine and ligation of varix, the patient recovered from this
      hypotensive event. No neurological deficit developed postoperatively. Portal
      hypertension results from increased resistance to portal venous blood flow or
      increased portal venous blood flow. Therefore, increased intravascular volume may
      play a significant role in precipitating variceal hemorrhage. In this case,
      abrupt circulatory change due to inadequate depth of anesthesia may partly cause
      massive hemorrhage. In conclusion, since potential adverse effects of increased
      blood volume and hepatic resistance on variceal hemorrhage must be considered
      during anesthesia, patients with episode of variceal hemorrhage should be treated
      as full stomach although endoscopic findings before the surgery indicate
      controlled hemorrhage from varix.

PMID- 9251520
TI  - [A case of twice catastrophic pulmonary vasoconstriction-type shock induced with
      protamine sulfate].
AB  - A 71-year-old female was scheduled for the re-replacement of a mechanical mitral
      valve. After the cardiopulmonary bypass (CPB) she was administered protamine
      sulfate. Subsequently mean systemic blood pressure went down below 20 mmHg and
      central venous pressure and mean pulmonary blood pressure were above 50 mmHg, and
      immediately CPB was restarted as an assist device for circulation. After the
      second CPB, she was administered protamine sulfate again, and the same shock
      occurred. At last the third CPB was restarted and the third protamine
      administration was not undertaken after the third CPB. Although her postoperative
      drainage may have been relatively much more compared with cases of neutralization
      of heparin, postoperative course was uneventful in this patient. Administered
      protamine to neutralize the anticoagulat effects of heparin may often cause
      temporary treatable hypotension. Although protamine may rarely cause severe
      pulmonary vasocontriction and anaphylactoid reactions, clinical pictures become
      critical once these reactions occur. It is important in these cases to identify
      protamine as the cause of shock and avoid repeating the shocks.

PMID- 9251521
TI  - [A case of prosthetic valve malfunction found by transesophageal echocardiography
      soon after the termination of cardiopulmonary bypass].
AB  - We present a case of mitral prosthetic valve malfunction soon after the
      termination of cardiopulmonary bypass. One leaflet of the St. Jude prosthetic
      mitral valve was found immobilized in the closed position during diastole by
      transesophageal echocardiography, with no abnormal hemodynamic changes. We
      started cardiopulmonary bypass again, and removed residual chordae. TEE is an
      essential tool for evaluating prosthetic valve function after the valve
      replacement.

PMID- 9251522
TI  - [A new technique of extubation using laryngeal mask in the neurosurgical
      anesthesia].
AB  - Recently we experienced two cases of multiple cerebral aneurysms for the
      aneurysmal neck clipping operation. In these cases, as these aneurysms can not be
      clipped primarily, the patient may still be susceptible to the rupture of
      remaining aneurysm after operation. Frequent bucking and hypertension occurring
      during extubation and emergence from anesthesia, can lead to intracranial
      hemorrhage and increases of intracranial pressure. To reduce this hemodynamic
      responses, several studies have been reported, but techniques in those papers are
      not sufficient to prevent the bucking perfectly, and the anesthesiologist has to
      hold the face mask forcefully for a long time after operation. The laryngeal mask
      airway (LM) seemed preferable for prevention of bucking and attenuation of
      cardiovascular response. Therefore, we tried to use LM at the emergence from
      anesthesia. After surgery, tracheal tube was removed at the deep level of
      anesthesia, and LM was inserted. After muscle relaxant was reversed, oxygen,
      nitrous oxide, and 0.3-0.5% sevoflurane were administered until spontaneous
      breathing became adequate. When sufficient breathing volume was confirmed, all
      anesthetic agents were terminated, and LM was removed after ascertaining
      swallowing motion. No bucking and serious hypertension were seen during the
      procedures, and the patient recovered uneventfully.

PMID- 9251524
TI  - [Is TLFB method applicable to Japanese drinking population?: a methodological
      study on measurement of alcohol consumption].
AB  - In order to measure alcohol related problems, it is fundamental task to begin
      with to know the drinking quantity of the people. This study tries to explore the
      comparative, methodological possibilities of Timeline Follow Back (TLFB) as well
      as Self-Monitoring (SM) methods to measure drinking quantity, using the sample of
      Japanese and Sri Lankans. Especially TLFB method has not being so far utilized in
      Japan for this purpose. This pilot study has done in two stages. In the first
      stage, it has focused to get data on the correct drinking quantity up to two
      months period. After analyzing data of the first pilot survey, it was decided to
      reduce in the second-staged study the time frame to obtain data on drinking
      quantity only up to one month period. In the second-staged study, 37 Japanese and
      36 Sri Lankans living in Japan has been selected. Results show that it is more
      appropriate SM method than TLFB method to investigate drinking quantity of the
      Japanese. Further it was evidenced that in order to employ TLFB method to
      investigate correct drinking quantity of the general Japanese population, it has
      to be further improved for overcoming ambiguity of respondents' memory on their
      alcohol consuming behavior. Moreover, it is understood that some characteristic
      drinking behaviors, influenced by Japanese drinking culture may be another
      barrier in getting correct drinking quantity data. However, the hypothesized
      notion of this cultural barriers was not supported. An alternative hypothesis
      "reflexive sensitivity to drinking", was implied.

PMID- 9251523
TI  - [Labor status of anesthesia in general hospitals in Japan Committee on Human
      Resources, the Japan Society of Anesthesiology].
AB  - AIMS: Investigating the labor by anesthetists in general hospitals with more than
      600 beds during the month of September 1995. METHOD: Using MS/EXCEL spread sheet
      soft wear, we have analyzed daily OR anesthesia activities in 33 hospitals based
      on personal attendance of anesthesiologists. We defined anesthesia performing
      hours i.e. actual working hours as the time between the onset and the end of
      anesthesia for each anesthetist. RESULTS: An average number of monthly anesthesia
      cases was 961 in the first 10 hospitals we surveyed. We obtained two frequency
      graphs on weekly 5-day working 138 anesthetists whose anesthesia performed, and
      their occupied hours were as shown in fig. 1 and 2. for those who worked other
      less than 5 days per week, they showed the shorter hours on the frequency
      distribution graph as shown in fig. 3 to 7. The 5-day working anesthetists have
      spent more than 5 hours giving anesthesia in the 93.2% of all anesthesia times in
      the first 10 hospitals, while 28.1% of the times in the last 10 hospitals. There
      were an average of 11.6 operating tables, in the first 10 hospitals. And we have
      analyzed ratios of the number of 5 day working persons to the number of operating
      tables. The ratio was 0.86 in the first 10 hospitals, while 0.21 in the last 10
      hospitals. CONCLUSIONS: There must be overwork of 5-day working anesthetists, who
      are working for too many hours for anesthesia. It is necessary to have better
      quality service in the OR.

PMID- 9251525
TI  - Liver cytosolic aldehyde dehydrogenase (ALDH1) polymorphism and its inheritance
      in Wistar rats.
AB  - Rats are very important experimental animal to study alcohol related problems.
      Liver aldehyde dehydrogenases (ALDHs) which metabolize aldehydes are reported to
      have several isozymes which are distributed in mitochondrial, microsomal and
      cytosolic fractions. However, there is discrepancy on reports concerning
      properties of cytosolic ALDH from normal liver. We report here the liver
      cytosolic ALDH (ALDH1) polymorphism and its inheritance in Wistar rats.
      Isoelectrophoretic focusing technique reveals the three ALDH1 phenotypes (termed
      AA, AC and CC) which are inherited in accordance with Mendelian fashion,
      indicating the existence of two alleles, ALDH1A and ALDH1C. In the range of pI
      5.3 to 5.8, the AA phenotype possesses a major anodic band with pI 5.3 and CC
      phenotype also has a cathodic pI 5.8 band. In contrast, AC phenotype exhibits
      five bands with pIs of 5.3, 5.4, 5.5, 5.7 and 5.8. Intensity of these bands
      gradually diminishes from the main band with pI 5.5 to the both opposite ends.
      These findings suggest that AC phenotype as well as AA and CC types has a
      structure of tetramer which consist of the combination of subunit of the A and C
      gene products.

PMID- 9251526
TI  - [Clinical manifestation of volatile solvent psychosis].
AB  - To identify symptomatological characteristics of solvent psychosis, 9 cases of
      chronic thinner intoxication with psychitaric evidence during the abstinent
      period are studied. The results were as follows: 1) During intoxication, 7 cases
      had visual hallucinations and 3 cases had auditory hallucinations. 2) Eight cases
      had irritabilities or mood disturbances without thinner intoxication. 3) Four
      cases had convulsions or delirium which were observed only in the withdrawal
      period, suggesting that these symptoms might be withdrawal signs of thinner
      dependence. 4) Six cases had Schneiderian first rank symptoms such as auditory
      hallucinations (i.e. voices commenting, voices arguing), delusions of control
      (withdrawal of thought, thought insertion, influence of thought) and delusional
      perception. Hallucinations that appeared in acute intoxication with thinner in 5
      of the 6 cases, were second rank symptoms. Five of the 6 cases did not show
      negative symptoms (i.e. blunting of thought) and they could maintain good
      emotional contact with other. Symptoms of these 5 cases were different from those
      of schizophrenia or the flashback phenomenon of thinner dependence. These cases
      suggest that Schneiderian first rank symptoms and maintenance of emotional
      contact are important for diagnosis of volatile solvent psychosis.

PMID- 9251529
TI  - [Record breaking-AAOS 1997. 64th annual meeting American Academy of Orthopedic
      Surgeons, 13.-17. 02. 1997, San Francisco].

PMID- 9251530
TI  - Orthopaedic proceedings and dissertations, 1996, 1997. Abstracts.

PMID- 9251531
TI  - 4th International Conference on Preventive Cardiology jointly with the 37th
      annual meeting of the Council on Epidemiology and Prevention, American Heart
      Association. Montreal, June 29-July 3, 1997. Abstracts.

PMID- 9251532
TI  - European Federation of National Associations of Orthopaedics and Traumatology.
      Barcelona, Spain, April 24-27, 1997. Abstracts.

PMID- 9251533
TI  - American Association of Oral and Maxillofacial Surgeons (AAOMS) 79th annual
      meeting and scientific sessions. Seattle, Washington, September 17-21, 1997.
      Abstracts.

PMID- 9251534
TI  - Society for the Study of Fertility, British Fertility Society and British
      Andrology Society, joint meeting. York, 1997. Abstracts.

PMID- 9251535
TI  - Physician assisted suicide, euthanasia, or withdrawal of treatment.

PMID- 9251536
TI  - General practice fundholding and health care costs.

PMID- 9251537
TI  - London's healthcare services--again.

PMID- 9251538
TI  - The changing face of ectopic pregnancy.

PMID- 9251539
TI  - Indicators of clinical performance.

PMID- 9251540
TI  - Smoking crackdown by UK government.

PMID- 9251541
TI  - Half the deaths of young infants may be avoidable.

PMID- 9251542
TI  - Goodbye to the "hello nurse" in casualty departments.

PMID- 9251543
TI  - Ruling on interferon beta will hit all health authorities.

PMID- 9251544
TI  - Impact of postmenopausal hormone therapy on cardiovascular events and cancer:
      pooled data from clinical trials.
AB  - OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from
      published clinical trials that studied other outcomes of postmenopausal hormone
      therapy as some surveys have suggested that it may decrease the incidence of
      cardiovascular diseases and increase the incidence of hormone dependent cancers.
      DESIGN: Trials that compared hormone therapy with placebo, no therapy, or
      vitamins and minerals in comparable groups of postmenopausal women and reported
      cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22
      trials with 4124 women were identified. In each group, the numbers of women with
      cardiovascular and cancer events were summed and divided by the numbers of women
      originally allocated to the groups. RESULTS: Data on cardiovascular events and
      cancer were usually given incidentally, either as a reason for dropping out of a
      study or in a list of adverse effects. The calculated odds ratios for women
      taking hormones versus those not taking hormones was 1.39 (95% confidence
      interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and
      deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such
      results would have occurred if the true odds ratio were 0.7 or less. For cancers,
      the numbers of reported events were too low for a useful conclusion. CONCLUSIONS:
      The results of these pooled data do not support the notion that postmenopausal
      hormone therapy prevents cardiovascular events.

PMID- 9251545
TI  - Randomised, double blind, multicentre comparison of hydrochlorothiazide,
      atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of
      the HANE study. HANE Trial Research Group.
AB  - OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide,
      atenolol, nitrendipine, and enalapril in patients with mild to moderate
      hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double
      blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS:
      868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg)
      INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg
      hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n =
      218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not
      reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20
      mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice
      daily (step 3). The eight week titration phase was followed by an additional 40
      weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME
      MEASURES: Blood pressure by means of an automatic device with repeated
      measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%)
      was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%),
      or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%)
      than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly
      better than enalapril (42.7%). The treatment related dropout rate was higher (P <
      0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of
      superiority for antihypertensive effectiveness or tolerability of the "new"
      classes of antihypertensives (calcium channel blockers and angiotensin converting
      enzyme inhibitors). As these drugs are now widely used as treatment of first
      choice, our results further emphasise the need for studies confirming that they
      also reduce morbidity and mortality, as has been shown for diuretics and beta
      blockers.

PMID- 9251546
TI  - Inpatient deaths from acute myocardial infarction, 1982-92: analysis of data in
      the Nottingham heart attack register.
AB  - OBJECTIVE: To assess longitudinal trends in admissions, management, and inpatient
      mortality from acute myocardial infarction over 10 years. DESIGN: Retrospective
      analysis based on the Nottingham heart attack register. SETTING: Two district
      general hospitals serving a defined urban and rural population. SUBJECTS: All
      patients admitted with a confirmed acute myocardial infarction during 1982-4 and
      1989-92 (excluding 1991, when data were not collected). MAIN OUTCOME MEASURES:
      Numbers of patients, background characteristics, time from onset of symptoms to
      admission, ward of admission, treatment, and inpatient mortality. RESULTS:
      Admissions with acute myocardial infarction increased from 719 cases in 1982 to
      960 in 1992. The mean age increased from 62.1 years to 66.6 years (P < 0.001),
      the duration of stay fell from 8.7 days to 7.2 days (P < 0.001), and the
      proportion of patients aged 75 years and over admitted to a coronary care unit
      increased significantly from 29.1% to 61.2%. A higher proportion of patients were
      admitted to hospital within 6 hours of onset of their symptoms in 1989-92 than in
      1982-4, but 15% were still admitted after the time window for thrombolysis. Use
      of beta blockers increased threefold between 1982 and 1992, aspirin was used in
      over 70% of patients after 1989, and thrombolytic use increased 1.3-fold between
      1989 and 1992. Age and sex adjusted odds ratios for inpatient mortality remained
      unchanged over the study period. CONCLUSIONS: Despite an increasing uptake of the
      "proved" treatments, inpatient mortality from myocardial infarction did not
      change between 1982 and 1992.

PMID- 9251547
TI  - Increased brain serotonin function in men with chronic fatigue syndrome.

PMID- 9251548
TI  - How has fundholding in Northern Ireland affected prescribing patterns? A
      longitudinal study.
AB  - OBJECTIVE: To compare prescribing patterns in general practices before and after
      the introduction of fundholding in April 1993 to determine whether fundholding
      changed prescribing patterns among practices that joined the scheme. DESIGN:
      Analysis of prescribing data from the Drug Utilisation Research Unit's database
      for all practices in Northern Ireland during April 1989 to March 1996. SETTING:
      Northern Ireland. SUBJECTS: 23-first wave fundholders, 34 second wave
      fundholders, 9 third wave fundholders, and 268 non-fundholders. MAIN OUTCOME
      MEASURES: Prescribing costs per 1000 patients, prescription items per 1000
      patients, average cost per item, and rate of generic prescribing. RESULTS:
      Prescribing costs and frequency increased in all groups throughout the study.
      Among the fundholders the rate of increase in costs after fundholding was
      significantly lower than among non-fundholders. The rate of increase in cost per
      item fell, coinciding with a significant increase in the rate of generic
      prescribing. However, with regard to first wave fundholders, their yearly
      increase in costs in their third year as fundholders (1995-6) was similar to that
      of the non-fundholders. The earlier practices that joined the scheme seemed to
      differ in some important respects from those that joined later. CONCLUSIONS:
      After fundholders joined the fundholding scheme their patterns of prescribing
      changed compared with those of non-fundholders: the rate of increase in costs
      fell and there was a significant rise in the rate of generic prescribing.

PMID- 9251549
TI  - What is to be done about fundholding?

PMID- 9251550
TI  - Fortnightly review. Plantar fasciitis.

PMID- 9251551
TI  - ABC of mental health. Disorders of personality.

PMID- 9251552
TI  - How to read a paper. The Medline database.

PMID- 9251553
TI  - Self monitoring of glucose by people with diabetes. Urine testing provides only
      historical information.

PMID- 9251554
TI  - Self monitoring of glucose by people with diabetes. Self monitoring improves
      quality of life and prognosis of people with diabetes.

PMID- 9251556
TI  - Self monitoring of glucose by people with diabetes. Patients with non-insulin
      dependent diabetes should monitor urine urine rather than blood glucose.

PMID- 9251555
TI  - Self monitoring of glucose by people with diabetes. Self monitoring is vital for
      people with impaired awareness of hypoglycaemia.

PMID- 9251557
TI  - Multiple myeloma. Surgery is often more effective than analgesia for mechanical
      pain.

PMID- 9251558
TI  - Multiple myeloma. Surgical stabilisation often provides good pain relief.

PMID- 9251559
TI  - Catheters smaller than 24 French gauge can be used for chest drains.

PMID- 9251560
TI  - Screening for prostate cancer. Randomised trials of treatment in early disease
      are important.

PMID- 9251561
TI  - Screening for prostate cancer. Early screening is important despite lack of data
      from trials.

PMID- 9251562
TI  - Trials of streptokinase in stroke depend on early, accurate diagnosis.

PMID- 9251563
TI  - Tuberculosis treatment is expensive for patients in developing countries.

PMID- 9251564
TI  - Alcohol consumption may influence onset of the menopause.

PMID- 9251565
TI  - Chronic venous ulcer. Some references may be misleading.

PMID- 9251566
TI  - Chronic venous ulcer. Hyperbaric oxygen treatment is a cost effective option.

PMID- 9251567
TI  - Chronic venous ulcer. Causes are often multifactorial and a holistic approach is
      required.

PMID- 9251568
TI  - Counselling should be provided before parents are told of presence of
      ultrasonographic "soft markers" of fetal abnormality.

PMID- 9251569
TI  - Harm resulting from screening is likely to be high where prevalence of breast
      cancer is low.

PMID- 9251570
TI  - Minimising factitious hyperkalaemia. Samples should be centrifuged after
      collection in general practices.

PMID- 9251571
TI  - Minimising factitious hyperkalaemia. Centrifuging samples may help prevent false
      readings.

PMID- 9251572
TI  - HIV positive doctors deserve support.

PMID- 9251573
TI  - Support and treatment of serious comorbidity also improve survival in breast
      cancer.

PMID- 9251574
TI  - Man's fractured sternum was probably due to snake's weight when it fell.

PMID- 9251575
TI  - Re: AP Boulet, G Tessier. Reference-based pricing in British Columbia:
      implications for cardiologists--an analysis. 1997; 13:46-51.

PMID- 9251576
TI  - Adult patients' knowledge about their congenital heart disease.
AB  - OBJECTIVE: To assess patient knowledge about their congenital cardiovascular
      disease. DESIGN: Fifty consecutive patients (25 women) attending the Adult
      Congenital Heart Disease Clinic, University of Alberta, Edmonton, Alberta, filled
      out a questionnaire that tested knowledge about their heart defect and
      endocarditis prophylaxis. The patients ranged in age from 18 to 60 years (mean
      25). The most frequent cardiovascular anomalies were obstruction of the left
      ventricular outflow tract (13), coarctation of the aorta (10), tetralogy of
      Fallot (six), transposition of the great arteries (five) and Marfan syndrome
      (four). Patients had been seen on average by three cardiologists (range one to
      six) and had made an average of seven clinic visits (range one to 22) since the
      age of 17 years. Eight patients had been followed at other clinics in the past.
      MAIN RESULTS: Fifty-four per cent of patients knew their diagnosis. Forty-four
      per cent could explain the defect in lay language, and another 48% made an
      attempt. When given a heart diagram, 26% marked their defect correctly and 28%
      made an attempt. Terms 'endocarditis' and 'antibiotic prophylaxis' were known to
      16% and 22% of patients, respectively. Fifty-eight per cent could name at least
      one situation that carries a risk of 'infection in the heart'. CONCLUSION: Adults
      with congenital heart disease have poor knowledge of their heart defects and the
      importance of endocarditis and antibiotic prophylaxis. Although time consuming,
      patient education should be a part of every clinic visit. Repetitive and
      structured patient education may improve patients' knowledge and, hence,
      participation in their health care.

PMID- 9251577
TI  - Long-term survival and functional status in the elderly after cardiac surgery.
AB  - BACKGROUND: Hospital mortality and morbidity of cardiac surgery have been well
      described in the elderly, but there is a paucity of data regarding long-term
      functional status. OBJECTIVE: To evaluate long-term survival and functional
      status of patients aged 70 years or older after cardiac surgery. DESIGN:
      Retrospective observational study. SETTING: University-affiliated tertiary care
      hospital. PATIENTS: Three hundred and twenty-nine consecutive patients aged 70 or
      older who had undergone cardiac surgery from January 1990 to December 1993.
      INTERVENTIONS: Besides postoperative mortality and morbidity, data regarding long
      term survival and functional status and preoperative variables affecting these
      outcomes were analyzed. MAIN RESULTS: Mean age at surgery was 73.9 +/- 2.9 years,
      and 70.2% of the procedures were performed on an urgent basis. Postoperative
      mortality was 9.4%. Five-year Kaplan-Meier survival in postoperative survivors
      was 85.9% and is comparable with the survival of the general sex- and age-matched
      Quebec population. Preoperative variables affecting long-term survival were
      atrial fibrillation (RR 3.8; 95% CI 1.4 to 10.0), smoking status on admission (RR
      3.6; CI 1.6 to 8.1), peripheral vascular disease (RR 2.9; CI 1.4 to 6.2) and low
      creatinine clearance (RR 1.4; CI 1.1 to 1.7). Functional status evaluated by the
      Karnofsky score showed a successful functional outcome in 84.6% of patients at
      follow-up (mean 2.6 +/- 1.1 years). Preoperative variables unfavourably
      influencing a successful functional outcome were hypertension (OR 0.34; CI 0.15
      to 0.76), cerebrovascular disease (OR 0.35; CI 0.15 to 0.87) and low creatinine
      clearance (OR 0.73; CI 0.55 to 0.96). CONCLUSIONS: Despite severe cardiovascular
      and often urgent conditions, sustained functional improvement and good long term
      survival can be objectively documented in most elderly patients after cardiac
      surgery.

PMID- 9251578
TI  - Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition
      and remodelling during healing after transmural canine myocardial infarction.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition for six weeks after
      myocardial infarction (MI) lowers the collagen content of infarct scars in dogs.
      However, temporal changes in collagen content of the infarct zone (IZ) with ACE
      inhibition during healing over six weeks after MI and their possible relation to
      IZ remodelling have not been determined. METHODS: IZ collagen (hydroxyproline)
      was measured over six to seven weeks in dogs treated with captopril (50 mg bid),
      enalapril (2.5 mg bid) or placebo, beginning on the second day following
      transmural anterior MI (or sham). In vivo changes in IZ and global left
      ventricular (LV) remodelling, mass and function (echocardiograms) and
      hemodynamics among six-week survivors were also measured. RESULTS: Compared with
      placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks.
      Among the six-week survivors, both inhibitors lowered IZ collagen (P < or =
      0.001) and increased the collagen type I:III ratio. However, preload was lower,
      increase in diastolic volume and mass were less and systolic function improved.
      Although the doses of captopril (but no enalapril) decreased afterload,
      inhibition of IZ collagen was less, IZ bulging and global LV dilation were less
      and systolic function was better with captopril than with enalapril. In all three
      MI groups, deaths over the seven weeks correlated with greater infarct size, LV
      volume and dysfunction and lower IZ collagen. CONCLUSIONS: ACE inhibition
      suppresses the temporal increase in IZ collagen and attenuates IZ expansion,
      thinning and bulging, and LV enlargement and aneurysm formation during healing
      after MI.

PMID- 9251579
TI  - Antioxidant enzymes and atherosclerosis in Japanese quail: heritability and
      genetic correlation estimates.
AB  - OBJECTIVES: To estimate, in male quail susceptible to atherosclerotic plaque
      formation (SUS) fed a regular diet and an atherogenic diet, the genetic and
      phenotypic parameters associated with antioxidant enzymes and atherogenesis.
      DESIGN: Genetic parameters were estimated from variance components of the
      analysis of variance on 70 males from 13 full-sib families. MAIN RESULTS: Under
      the regular diet, seven of 35 males developed mild atherosclerosis. Heritability
      was zero for atherosclerotic plaque score and plasma cholesterol level. Plaque
      score was highly correlated to plasma triglyceride level (rp = 0.96) and liver
      fattiness (rp = 0.97), but only moderately to plasma cholesterol level (rp =
      0.39). With the high cholesterol diet, plasma cholesterol level increased sixfold
      and became heritable (h2 = 0.4). Many males developed severe atherosclerosis.
      Plaque score became associated more with plasma and aortic cholesterol levels (rp
      = 0.56) and 0.76, respectively) than with plasma triglyceride level (rp = 0.54).
      Aortic glutathione reductase activity was negatively correlated with plaque score
      (rp = -0.42; rg = -0.51) and aortic cholesterol level (rp = -0.39; rg = -0.62).
      CONCLUSIONS: Plasma triglyceride level was an important factor affecting the
      development of fatty streaks and the early progression of atherosclerotic
      plaques. Without high levels of dietary cholesterol in the plasma and aorta, any
      early atherosclerotic plaques that developed did not progress further within the
      time-frame of the experiment. Aortic cholesterol concentration and glutathione
      reductase activity were important factors in the advancement of severe plaque
      formation. Heritability of plaque score was high in the SUS line, and further
      selective breeding should increase the susceptibility of these quail to
      cholesterol-induced atherosclerosis.

PMID- 9251580
TI  - Stenting of the left main coronary artery in the setting of acute myocardial
      infarction.
AB  - Coronary artery bypass grafting is the treatment of choice for significant left
      main coronary artery disease. A patient with an occluded left main coronary
      artery in the setting of myocardial infarction, who was given streptokinase and
      subsequently managed with intracoronary stenting, is reported.

PMID- 9251581
TI  - Echocardiographic detection of pulmonary embolism in transit: implications for
      institution of thrombolytic therapy.
AB  - Right atrial or ventricular thrombi in patients with pulmonary embolism are
      emboli in transit and are a medical emergency because they are associated with a
      high mortality rate when treated conservatively with anticoagulation. The current
      standard therapy is less well accepted because of the risk of clot fragmentation
      and distal embolization. A case in which an unsuspected right ventricular
      thrombus was diagnosed by echocardiography is reported. This findings led to
      treatment with streptokinase (250,000 U, followed by 100,000 U/h for 24 h).
      Clinical improvement was rapidly obtained and the thrombus disappeared 10 h after
      the initial study. There was no complication. The case illustrates the utility of
      two-dimensional enchocardiography in the evaluation of patients with pulmonary
      embolic disease and the efficacy and safety of thrombolytic therapy in the
      treatment of pulmonary embolism in transit.

PMID- 9251582
TI  - Reference-based pricing (RBP) of prescription drugs.

PMID- 9251584
TI  - Re: Prospective reinfaction outcomes in the Thrombolytic Era Cardizem CD Trial
      (PROTECT)

PMID- 9251585
TI  - Adjuvant therapy for colorectal cancer.

PMID- 9251586
TI  - Study of brain stem auditory-evoked potentials (BAEPs) and visual-evoked
      potentials (VEPs) in leprosy.
AB  - A study of brain stem auditory-evoked potentials (BAEPs) and visual-evoked
      potentials (VEPs) was done on 25 newly diagnosed patients with leprosy whose
      diagnosis was confirmed by skin biopsy. The results were compared with 25 age-
      and sex-matched healthy controls. In BAEPs the important observations were the
      prolonged latency of wave V in 13 (52%), delayed interpeak latency (IPL) of wave
      I-III in 5 (20%) cases, of wave III-V in 12/25 (40%), suggesting a conduction
      abnormality of the VIII cranial nerve in its peripheral part, in its nucleus and
      in its connection in the brain stem. In VEPs, a delayed peak latency of major
      positive potential (P100) was seen in 20 cases (80%; 11/13, 84.6% TT; 7/10, 70%
      LL; 2/2, 100% BL), suggestive of subclinical optic nerve involvement. The BAEPs
      and VEPs were both abnormal in 10 cases (40%; 3/13, 23% TT; 5/10, 50% LL; 2/2,
      100% BL). Conduction abnormalities of the central nervous system (CNS) were
      observed more frequently in lepromatous leprosy, as in other forms of peripheral
      neuropathy such as hereditary motor sensory neuropathy type I (HMSN I). There is
      a fair possibility of similar multiple demyelinating lesions in the CNS also, as
      is seen in leprous peripheral neuropathy. This hypothesis requires further
      strengthening by an extensive study of multimodality evoked potentials with
      magnetic resonance imaging in the patients. Histopathological and
      immunofluorescent studies of autopsy material of the brain can also contribute
      significantly to solve the dilemma.

PMID- 9251587
TI  - Auditory brain stem evoked potentials in patients with leprosy.
AB  - Nineteen, randomly selected male patients with lepromatous leprosy were evaluated
      electrophysiologically. All of these patients had long-standing disease and were
      treated with dapsone alone. There were statistically significant differences
      between the values obtained in this group of leprosy patients compared to 20 age
      matched controls in auditory brain stem evoked potentials (ABEP). The findings
      are consistent with a pathologic process located mainly between the cochlear
      nucleus and the lateral lemniscus in the auditory brain stem pathways. It should
      be emphasized that our patients had long-standing disease which was treated with
      dapsone. ABEP could very well be different in leprosy patients diagnosed early
      and treated for relatively short periods with multidrug therapy. Brain stem
      evoked response audiometry may be useful for evaluating the possibility of brain
      stem involvement in leprosy.

PMID- 9251588
TI  - Cervical branch of the facial nerve in leprosy.
AB  - This study demonstrates that the platysma is occasionally palsied in leprosy and
      that this only occurs when the facial nerve already has some other palsy. That
      there needs to be a facial palsy before there can be a platysma palsy is strongly
      suggested, in that there was no case of an isolated platysma palsy. Patients,
      regardless of age or other factors, could mimic a platysma contraction. This
      obviates the need for electrical testing to examine for a platysma palsy. It also
      means that a nonfunctioning platysma on clinical examination is, in fact, a
      palsied platysma. While lagophthalmos is regularly examined for, and any obvious
      facial paresis would be noticed, less severe forms of facial muscle paresis will
      only be found if formally examined for. The mechanism whereby the facial nerve is
      involved in leprosy is not clarified, but our findings suggest that proximal
      spread of a lesion that began in the zygomatico-temporal branches and reaches to
      the facial nerve trunk is more likely than new lesions developing de novo in
      other peripheral facial nerve branches. That the primary lesion is within the
      facial nerve trunk in all cases but we only see the frequent zygomatic sequelae
      due to secondary factors is not excluded.

PMID- 9251589
TI  - Humoral and cellular immune reactivity to recombinant M. leprae antigens in HLA
      typed leprosy patients and healthy controls.
AB  - In our search for Mycobacterium leprae antigens that might specifically induce
      immunity or immunopathology, we have tested both humoral and cellular immune
      reactivity against purified recombinant M. leprae antigens in 29 paucibacillary
      (PB), 26 multibacillary (MB) leprosy patients, and 47 matched healthy contacts.
      The following M. leprae antigens were tested: 2L-1 (65L-1, GroEl-1), 2L-2 (65L-2,
      GroEl-2), 4L (SoDA), 43L, 10L (B) and 25L (Sra). The individuals were also typed
      for HLAD-RB1 and DQB1 in order to see whether leprosy status and/or immune
      reactivity to these antigens might be associated with certain HLA types. We also
      tested sera from another 48 patients before, during and after multidrug therapy
      (MDT) to study the relationship between antibody reactivity to recombinant M.
      leprae antigens and MDT. Antibody titers to the four recombinant M. leprae
      antigens tested and to D-BSA were higher in MB patients compared to PB patients
      and healthy controls, and declined with treatment. From a diagnostic or
      monitoring point of view none of the recombinant antigens seemed to be an
      improvement over D-BSA, mainly due to the lower sensitivity. IgG subclasses were
      measured in positive sera of untreated patients. These were mainly of the IgG1
      and IgG3 subclasses, but subclass diversity was also observed and antigen
      dependent: all four subclasses could be detected against 10L (B), only IgG1 and
      IgG3 against 43L and only IgG1 against 25L and 2L-1. Cellular immune reactivity
      against the purified recombinant M. leprae antigens was measured in a lymphocyte
      stimulation test (LST). As for M. leprae, there was an inverse correlation
      between antibody and T-cell reactivity. However, the number of LST responders to
      recombinant antigens was much lower than to M. leprae. The 43L antigen was
      recognized most often (19%-24% of individuals tested) and more often than the 10L
      (B) antigen (10%-12%). No clear correlation was observed with leprosy type or
      protection and, in general, M. leprae nonresponders were also negative with
      recombinant antigens. Finally, we confirmed that HLA-DRB1*02 is associated with
      leprosy in this population, and we observed an association between DQB1*0601 and
      lepromatous leprosy. The number of positive individuals was too small to allow a
      meaningful analysis of the relationship between HLA type and immune reactivity.
      Although these data do not allow a conclusion as to one of these purified
      recombinant antigens being either protection or disease related, the antigen
      dependent IgG subclass diversity warrants further study on antigen-specific
      qualitative differences in immune reactivity that may be relevant for the outcome
      of an infection with M. leprae.

PMID- 9251590
TI  - Associations between HLA-DRB1 alleles and leprosy in an Indonesian population.
AB  - To investigate whether the susceptibility to leprosy (type), subclinical
      infection with Mycobacterium leprae and the antibody response against M. leprae
      specific antigens are associated with HLA-DR phenotypes sequence-specific
      oligonucleotide HLA-DRB1 and DQA1 typing and antibody assays have been performed
      in 79 leprosy patients (41 TT/BT and 38 LL/BL) and 50 healthy controls from a
      Javanese population in Yogyakarta, Indonesia. DRB1*02 was associated with LL/BL
      [odds ratio (OR) 2.54, 95% confidence interval (CI) 0.97-9.78, p = 0.037 and
      attributable risk (AR) 41.5%] but not with TT/BT leprosy (p > 0.05). HLA-DRB1*12
      was negatively associated with leprosy (either LL/BL or TT/BT [OR 0.33-0.35, p <
      0.05, prevented fraction (PF) 58.8%-65.3%]. No significant association was found
      between HLA-DRB1 or DQA1 type, anti-M. leprae antibody level and subclinical
      infection with M. leprae. These data indicate that in this population
      susceptibility to lepromatous leprosy is associated with HLA-DRB1*02, while
      resistance to leprosy is associated with HLA-DRB1*12. These associations are not
      paralleled with associations of the same HLA types with anti-M. leprae antibody
      level. Finally, the results of this study also support the notion that infection
      with M. leprae per se is not associated with HLA-DRB1 or DQA1 alleles.

PMID- 9251592
TI  - Association between leprosy and HIV infection in Tanzania.
AB  - SETTING: An epidemiological study of the interaction of leprosy and HIV infection
      in Tanzania. OBJECTIVE: To establish the prevalence of HIV infection among
      leprosy patients, and to measure the association of HIV and leprosy by comparing
      the HIV prevalence in leprosy patients and blood donors. DESIGN: Testing for HIV
      infection in consecutively diagnosed leprosy patients (new and relapsed after
      MDT) in all regions in Tanzania successively for a period of 3 to 6 months during
      1991, 1992 and 1993. RESULTS: Out of the total estimated eligible leprosy
      patients, 697 patients (69%) entered the final analysis. The HIV prevalence among
      these leprosy patients was 12% (83/697) as compared to 6% (8960/ 158,971) in
      blood donors examined in Tanzania during the same period. There were no
      significant differences in HIV seroprevalence by age, sex, residence or type of
      disease. However, the adjusted odds ratio (OR) of the presence of a BCG scar was
      1.9 [95% confidence interval (CI) 1.1-3.3] among HIV-positive leprosy cases
      compared to HIV-negative leprosy cases. Comparing leprosy cases with blood donors
      as controls, the logistic regression model, controlling for sex, age group and
      residence, showed the OR for HIV seropositivity among leprosy patients to be 2.5
      (95% CI 2.0-3.2). This association existed in all strata, but was strongest in
      the 15-34-year age group. No difference of HIV status between multibacillary and
      paucibacillary leprosy could be shown to exist. The point estimate of the
      population attributable risk of HIV infection for leprosy was 7%. CONCLUSION: HIV
      infection is associated with leprosy and might reverse the epidemiological trend
      of the slow decline in case notification in Tanzania if HIV infection is
      increasing greatly. Previous BCG vaccination loses its protection against leprosy
      in the presence of HIV infection. A repeated study is recommended in order to
      validate these findings, whereby recording of the disability grading of the cases
      is necessary to adjust for delay in diagnosis.

PMID- 9251593
TI  - Comparison of bacillary indexes in slit-skin smears, skin and nerve biopsies; a
      study from Malawi.
AB  - Data analyzed in this paper were collected within the framework of the Lepra
      Evaluation Project, an epidemiological study of leprosy in Karonga District,
      northern Malawi. For 212 patients information on the number of skin lesions, slit
      skin smear and skin biopsy results were available. Among 61 patients with a
      single lesion none were slit-skin-smear positive and two had bacilli detected in
      skin biopsies. In contrast, among 119 patients with four or more lesions 34
      (28.6%) versus 59 (49.6%) had bacilli detectable in slit-skin smears or skin
      biopsies, respectively. In a further 47 patients skin biopsy results could be
      compared with split-nerve biopsy results. In 20 of 47 patients the bacterial
      indexes (BIs) were identical in skin and nerve biopsies, while in 26 of 47
      patients the BIs were higher in nerve than in skin biopsies. This difference,
      which is consistent with several other studies in the literature, provides an
      insight into the pathogenesis of leprosy.

PMID- 9251591
TI  - No evidence for linkage between leprosy susceptibility and the human natural
      resistance-associated macrophage protein 1 (NRAMP1) gene in French Polynesia.
AB  - In order to determine whether a human homolog (NRAMP1) to a murine candidate gene
      for resistance to mycobacteria influences susceptibility to human disease, we
      analyzed data from seven multicase leprosy families (84 individuals) from French
      Polynesia for linkage markers within the NRAMP1 gene and leprosy per se.
      Individual family members were typed at nine polymorphic loci within NRAMP1. In
      addition, three physically linked, polymorphic microsatellite markers-D2S104,
      D2S173 and D2S1471-were also typed. Linkage analyses were done using affected
      sibpair and LOD score methods employing different modes of inheritance with full
      and reduced penetrance. The results of this study strongly suggest that NRAMP1 is
      not linked to leprosy susceptibility in the French Polynesian families tested.

PMID- 9251594
TI  - Monitoring steroid use in a field program; possible process indicators.
AB  - Two new indicators are proposed in order to make the task of monitoring certain
      prevention of disability (POD) activities more straightforward. The indicators
      are very similar to the case detection rates and the cohort analyses already used
      in both leprosy and tuberculosis (TB) control; this makes them very simple to put
      into practice. Despite their simplicity, it is argued that these indicators can
      give important information about the implementation of POD activities in a
      routine field program and could, therefore, help in improving the quality of
      those services to patients. The indicators are the steroid start rate (SSR) and
      the steroid completion rate (SCR). A number of possible confounding factors have
      been looked at and they are not negligible. However, the case detection rates for
      new cases of leprosy and treatment completion rates for multidrug therapy (MDT)
      are subject to similar biases, which are well recognized and which have not
      detracted from the usefulness of these indicators in evaluating leprosy control
      activities. The POD indicators, if used with an awareness of the possible biases
      involved, can help to improve the quality of certain POD activities.

PMID- 9251595
TI  - Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg
      ofloxacin and 100 mg minocycline for the treatment of leprosy; first results.
AB  - In 1995, a field trial was implemented in Senegal in order to evaluate the
      efficacy of a regimen based on the monthly supervised intake of rifampin 600 mg,
      ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During the first year
      of the trial, 220 patients with active leprosy (newly detected or relapsing after
      dapsone monotherapy) were recruited: 102 paucibacillary (PB) (60 males and 42
      females) and 118 multibacillary (MB) (71 males and 47 females). All of them
      accepted the new treatment (none requested to be preferably put under standard
      WHO/MDT), no clinical sign which could be considered as a toxic effect of the
      drug was noted, and none of the patients refused to continue treatment because of
      any clinical trouble. The compliance was excellent: the 113 patients (PB and MB)
      detected during the first 6 months of the trial have taken six monthly doses in 6
      months, as planned. The rate of clearance and the progressive decrease of
      cutaneous lesions was satisfactory. Although it is too soon to give comprehensive
      results, it should be noted that no treatment failure was observed in the 56 PB
      patients who have completed treatment and have been followed up for 6 months. The
      long-term efficacy of the new regimen is to be evaluated on the rate of relapse
      during the years following the cessation of treatment. If that relapse rate is
      acceptable (similar to that observed in patients after treatment with current
      standard WHO/ MDT), the new regimen could be a solution to treat, for instance,
      patients very irregular and/or living in remote or inaccessible areas since no
      selection of rifampin-resistant Mycobacterium leprae should be possible (a
      monthly dose of ofloxacin and minocycline being as effective as a dose of dapsone
      and clofazimine taken daily for 1 month). Nevertheless, until longer term results
      of this and other trials become available, there is no justification for any
      change in the treatment strategy, and all leprosy patients should be put under
      standard WHO/MDT.

PMID- 9251596
TI  - Fixed-duration multidrug therapy in multibacillary leprosy.
AB  - Six-hundred-fifty-seven active multibacillary (MB) leprosy patients were put on
      fixed-duration multidrug therapy (FD-MDT) between 1985 and 1992 (190 had had no
      and 235 had had previous treatment with dapsone) and were followed for 5 years
      after therapy. Two relapses occurred during year 5 of surveillance and both had
      received dapsone prior to chemotherapy, giving an overall relapse rate of
      0.08/100 person-years (py). Excluding the two relapses, 99.4% of the MB patients
      converted to smear negativity at year 6 after a regular course of FD-MDT. The
      relapse rate for 35 MB patients with an initial bacterial index (BI) of > 4 with
      5 years of surveillance was 0.24/100 py. Reactions occurred more frequently
      during the first 6 months of MDT, decreasing gradually thereafter, and reaching 0
      in year 4 of surveillance. The deformity rate at intake was 22.7% and only 1.8%
      of MB patients developed new deformities or an increased grade in deformity
      during therapy.

PMID- 9251597
TI  - Risk of relapse in leprosy after fixed-duration multidrug therapy.
AB  - Between 1986 and 1995, 8307 leprosy patients have completed fixed-duration
      multidrug therapy (FD-MDT) and were followed annually for possible relapse. The
      mean relapse rate for multibacillary (MB) leprosy is 0.15/1000 person-years (py)
      and for paucibacillary (PB) 0.55/1000 py. There is no difference in the relapse
      rates between patients with or without chemotherapy before FD-MDT. In MB
      patients, the five relapses occurred between 4 and 7 years; in PB patients, five
      relapses occurred at 4-5 years after FD-MDT. Six additional PB relapses self
      reported 1-4 years after the 5-year surveillance period and were not included in
      the relapse rates. Most PB patients relapsed into MB due to wrong classification
      and insufficient therapy. For the known 62 irregular MB patients the cumulative
      relapse rate is 6.5%.

PMID- 9251598
TI  - An anatomist in leprosyland.

PMID- 9251599
TI  - The influence of the San Lazaro Hospital of Seville in the creation and
      management techniques of the "lazaretto" hospitals in the Americas.
AB  - The San Lazaro Hospital of Seville that was established in the middle of the 13th
      century was one of the most important in Spain and Europe throughout nearly eight
      centuries in terms of caring for leprosy patients. In the 1930s the exclusive
      treatment of leprosy patients ceased and San Lazaro became a general hospital.
      The Spanish Crown (Alfonso X) accorded certain privileges and rules to the
      hospital which also were conferred by subsequent monarchs. These rules and
      ordinances contributed to the establishment and functioning of many lazarettos
      throughout the Americas of which we have documentation, notably those of Santo
      Domingo, Tlaxplana (Mexico City), Lima, Cartagena de Incias, La Habana, and
      Yucatan.

PMID- 9251600
TI  - Regarding Brasil, et al.'s adverse effects in leprosy's WHO/MDT and paramedic's
      role in leprosy control program.

PMID- 9251601
TI  - Acute renal failure and multidrug therapy for leprosy.

PMID- 9251602
TI  - Bacillary and histopathological findings in the peripheral nerves of armadillos
      experimentally infected with M. leprae.

PMID- 9251603
TI  - Dapsone-induced motor polyneuropathy in a patient with leprosy.

PMID- 9251604
TI  - Rate of decline in bacterial index in leprosy; observations after three different
      chemotherapeutic interventions.

PMID- 9251605
TI  - Do we need more specialization?

PMID- 9251606
TI  - The "anchored disc phenomenon": a proposed etiology for sudden-onset, severe, and
      persistent closed lock of the temporomandibular joint.
AB  - This article establishes a rationale for a particular type of sudden and severely
      restricted mouth opening caused by anchoring of the disc to the fossa termed
      anchored disc phenomenon, describes the possible pathogenesis of this disorder,
      and recommends appropriate treatment. The clinical characteristics supporting the
      proposed pathogenesis, and treatment of the disorder are based on data published
      in the literature and clinical experience with the diagnosis and treatment of
      this disorder.

PMID- 9251607
TI  - Sinus inlay bone augmentation: comparison of implant positioning after one- or
      two-staged procedures.
AB  - PURPOSE: This study was undertaken to compare implant angulation and position
      after one- or two-stage sinus inlay bone augmentation. PATIENTS AND METHODS:
      Twenty patients were retrospectively selected; group 1 (n = 10) was operated on
      with a one-stage procedure, and group 2 (n = 10) with a two-stage operation.
      Casts processed for the final permanent or temporary bridgework were collected
      and photographed from an oblique anterior view paralleling the alveolar crest on
      the right and left sides, as well as from an occlusal view. The angle between
      impression pins inserted in the abutments relative to the true vertical was
      recorded. In the occlusal view, the midpoints of the abutments were related to an
      individual computerized superimposed parabola. RESULTS: The implants inserted
      during the one-stage procedure were generally placed more palatally (Wilcoxon
      rank sum test, P = .0101) and angled more palatally (P = .0009) compared with
      those placed with the two-stage operation. CONCLUSION: This study showed that the
      two methods of treating patients by sinus inlay bone augmentation differed
      significantly with regard to placement and angulation of the implants. A two
      stage procedure seems to offer the surgeon more optimal conditions for
      positioning the implants.

PMID- 9251608
TI  - Occlusal cant in the frontal plane as a reflection of facial asymmetry.
AB  - PURPOSE: The purpose of this study was to compare subjective evaluation of
      occlusal canting in frontal photographs with objective radiographic measurements
      to determine the threshold at which a cant is recognized as abnormal. PATIENTS
      AND METHODS: Standardized frontal photographs (at rest and smiling) of two groups
      of orthognathic surgery patients were evaluated. Group 1 consisted of patients
      with a documented occlusal cant (n = 21), and group 2 consisted of patients with
      no cant (n = 22). Four untrained and five trained observers independently, and
      blind to the diagnoses, assessed patient photographs to judge the presence or
      absence of canting. These subjective results were compared with objective
      measurements of the angle of the occlusal plane to the true horizontal on each
      patient's posteroanterior (PA) cephalogram. RESULTS: The mean occlusal cant was
      5.0 degrees +/- 1.6 degrees for group 1 and 1.4 degrees +/- 0.9 degree for group
      2. The difference between groups was statistically significant (P < .01). Cants
      greater than 4 degrees were detected clinically with greater than 90% frequency
      by both untrained and trained observers. CONCLUSIONS: The results of this study
      indicate that 4 degrees is the threshold for recognition of an occlusal cant by
      90% of observers. This information has significant implications for three
      dimensional planning and outcome assessment in orthognathic and craniofacial
      surgery.

PMID- 9251609
TI  - Lower lip cancer: Mohs micrographic surgery and reconstruction as a
      multidisciplinary effort.
AB  - Lower lip cancer treated as a multidisciplinary effort has advantages in cost
      savings, conservation of tissue, and tumor elimination. This article discusses
      the technique of eradication of the lesion by the Mohs micrographic surgeon and
      secondary reconstruction by the oral and maxillofacial surgeon, and illustrates
      the results of this cooperative effort.

PMID- 9251610
TI  - The relapse patterns and outcome of postoperative recurrent tongue cancer.
AB  - PURPOSE: The relapse patterns and salvage treatment results for patients who
      developed locoregional recurrence after surgery for squamous cell carcinoma of
      the tongue were retrospectively analyzed. MATERIALS AND METHODS: Between April
      1986 and January 1995, 77 cases with recurrent squamous cell carcinoma of the
      tongue were evaluated. Most of them were males in the early stages of initial
      disease. Although the surgical margins were negative in most cases (67 of 77),
      relapse eventually occurred. The relapse patterns showed 15 patients with primary
      recurrence, 45 patients with regional neck lymph node (LN) relapse, and 17
      patients with relapse in both sites. RESULTS: Salvage treatment was given to most
      of the patients, but their median survival time was only 9 months. Survival data
      were analyzed and compared with different types of relapse patterns, salvage
      treatments, disease-free intervals, age, and sex. In univariate analysis, the
      neck LN relapse and shorter relapse-free interval (< 6 months) were poor
      prognostic factors (P < .05), and surgical treatment showed a trend for better
      salvage results (P = .0575). In multivariate analysis, patients with neck LN
      relapse had the worst outcome (P < .05). CONCLUSIONS: Recurrence of tongue cancer
      is not uncommon, but there are little data in literature regarding the prognosis.
      Although this study showed poor salvage results, various prognoses could be
      predicted on the bases of the different relapse patterns and salvage methods.

PMID- 9251611
TI  - Vascularized bone flap for access to the maxillary sinus.
AB  - PURPOSE: This article describes a vascularized bony window for access to the
      maxillary sinus and reports the clinical results. PATIENTS AND METHODS: A bony U
      shaped window in the anterior sinus wall was pedicled on the surrounding soft
      tissue and periosteum. After the described sinus was cleared of disease, the
      window was repositioned in its original site either using resorbable sutures or
      not. The method was used in 47 maxillary sinus operations in 45 patients. Twenty
      four patients were followed-up for more than 48 months. RESULTS: The vascularized
      bony window technique showed uneventful healing in all patients and none of the
      24 patients reported any problems. CONCLUSIONS: The vascularized bony window
      technique provides a large antrostomy, which gives good access and visibility and
      results in satisfactory postoperative healing.

PMID- 9251612
TI  - Clinical trial of recombinant granulocyte colony-stimulating factor for
      chemotherapy-induced neutropenia patients with oral cancer.
AB  - PURPOSE: This study was undertaken to evaluate the efficacy and toxicity of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) in reducing
      neutropenia in patients with oral cancer undergoing intensive chemotherapy.
      MATERIALS AND METHODS: Patients with chemotherapy-induced neutropenia (< 1 x
      10(9)/L) were divided into two groups: control group (n = 13) and rhG-CSF
      administration group (n = 16). rhG-CSF was administered subcutaneously at a dose
      of 75 micrograms/day on consecutive days. Peripheral blood cell counts and oral
      complications were investigated in each group. RESULTS: The duration of
      neutropenia and absolute neutrophil nadir counts were significantly improved by
      administration of G-CSF. No consistent effect on thrombocytopenia was noted.
      Administration of rhG-CSF also reduced the duration and degree of oral
      complications associated with chemotherapy-induced neutropenia. Intolerable side
      effects associated with administration of rhG-CSF were not observed. CONCLUSION:
      It was concluded that rhG-CSF is effective in shortening the duration of
      neutropenia after chemotherapy at a dose of 75 micrograms/day.

PMID- 9251613
TI  - Persistent lip swelling.

PMID- 9251614
TI  - The person behind the name.

PMID- 9251615
TI  - Combined middle cranial fossa and preauricular approach to the temporomandibular
      joint: report of a case.

PMID- 9251616
TI  - Small-cell noncleaved non-Hodgkin's lymphoma of the mandible in previously
      unrecognized human immunodeficiency virus infection: report of a case.

PMID- 9251617
TI  - Asystole after inadvertent intubation of the orbit.

PMID- 9251618
TI  - Pseudoaneurysm of the lingual artery: a case report.

PMID- 9251619
TI  - Cervical cellulitis with mediastinitis from an odontogenic infection complicated
      by diabetes mellitus: report of a case.

PMID- 9251620
TI  - Eosinophilic granuloma of the mandibular condyle: report of three cases and
      review of the literature.

PMID- 9251621
TI  - Actinomycosis of the tongue associated with human immunodeficiency virus
      infection: case report.

PMID- 9251623
TI  - Surgical repair of the cleft earlobe.

PMID- 9251622
TI  - Management of a deep space infection of the neck in a patient with Glanzmann's
      thrombasthenia.

PMID- 9251624
TI  - A simplified technique for harvesting large buccal mucosal grafts.

PMID- 9251625
TI  - In defense of condylotomy.

PMID- 9251626
TI  - The MD degree: problem or solution?

PMID- 9251627
TI  - Estimating future workforce and training requirements for oral and maxillofacial
      surgeons. Patient Service Needs Committee of the American Association of Oral and
      Maxillofacial Surgeons.

PMID- 9251628
TI  - How do you sleep at night, Mr Broughton?

PMID- 9251629
TI  - Rheumatoid arthritis: not yet curable with early intensive therapy.

PMID- 9251630
TI  - Watchful waiting or drug therapy for benign prostatic hyperplasia?

PMID- 9251631
TI  - Hypersensitivity vasculitis--not always benign?

PMID- 9251632
TI  - Listeria meningitis in adults.

PMID- 9251633
TI  - Dearing--a report to be embraced.

PMID- 9251634
TI  - Randomised comparison of combined step-down prednisolone, methotrexate and
      sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.
AB  - BACKGROUND: The value of intensive combination therapy in early rheumatoid
      arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA),
      we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5
      mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5
      mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid
      arthritis (median duration 4 months) were randomly assigned combined treatment
      (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and
      stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled
      index (a weighted change score of five disease activity measures) and the
      Sharp/Van der Heijde radiographic damage score in hands and feet. Independent
      health-care professionals assessed the main outcomes without knowledge of
      treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI
      1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine
      group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively,
      were improved according to American College of Rheumatology criteria. The
      clinical difference between the groups decreased and was no longer significant
      after prednisolone was stopped, and there were no further changes after
      methotrexate was stopped. At 28 weeks, the radiographic damage score had
      increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0
      44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43]
      vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were
      also significant. Further analysis suggests that combined therapy immediately
      suppressed damage progression, whereas sulphasalazine did so less effectively and
      with a lag of 6 to 12 months. There were fewer withdrawals in the combined
      therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred
      later. INTERPRETATION: This combined-therapy regimen offers additional disease
      control over and above that of sulphasalazine alone that persists for up to a
      year after corticosteroids are stopped. Although confirmatory studies and long
      term follow-up are needed, this approach may prove useful in the treatment of
      early rheumatoid arthritis.

PMID- 9251635
TI  - Should women be advised against pregnancy after breast-cancer treatment?
AB  - BACKGROUND: Oestrogen is an established growth factor in breast cancer. There
      has, therefore, been much discussion about whether women should be advised
      against becoming pregnant after breast-cancer treatment because of a possible
      negative prognostic effect from the high oestrogen concentrations associated with
      pregnancy. METHODS: We studied 5725 women with primary breast cancer. Information
      on these women was obtained from the Danish Breast Cancer Cooperative Group.
      Since 1977 this group has collected population-based data on tumour
      characteristics, treatment regimens, and follow-up status of Danish women with
      breast cancer. Details of reproductive history were obtained from The Danish
      Civil Registration System, the National Birth Registry, and the National induced
      Abortion registry. We estimated the relative risk of death among women who became
      pregnant after breast-cancer treatment compared with women who had not become
      pregnant. FINDINGS: 5725 women with primary breast cancer aged 45 years of
      younger at the time of diagnosis were followed up for 35,067 patient-years. Among
      these, 173 women became pregnant after treatment of breast cancer. Women who had
      a full-term pregnancy after breast-cancer treatment had a non-significantly
      reduced risk of death (relative risk 0.55 [95% CI 0.28-1.06]) compared with women
      who had had no full-term pregnancy after adjustment for age at diagnosis, stage
      of disease (tumour size, axillary nodal status, and histological grading), and
      reproductive history before diagnosis. The effect was also not significantly
      modified by age at diagnosis, tumour size, nodal status, or reproductive history
      before diagnosis of breast cancer. Neither miscarriages nor induced abortions
      after breast-cancer treatment influenced the prognosis. INTERPRETATION: We found
      no evidence that a pregnancy after breast-cancer treatment increased the risk of
      a poor outcome.

PMID- 9251636
TI  - Resistance to methicillin and other antibiotics in isolates of Staphylococcus
      aureus from blood and cerebrospinal fluid, England and Wales, 1989-95.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) strains are
      colonising hospital patients in most areas of England and Wales, UK. The extent
      to which they cause invasive infection can be gauged from their presence in
      isolates from blood or cerebrospinal fluid. METHODS: About 200 clinical
      laboratories reported the results of susceptibility testing of between 4501 and
      6370 isolates of S aureus from blood or cerebrospinal fluid in each of the years
      1989-95. We assessed the rate of resistance to methicillin and other antibiotics
      for each of these years. FINDINGS: Resistance to methicillin was stable at about
      1.5% of isolates during 1989-91, but increased thereafter to 13.2% in 1995 (p <
      0.001). At the same time there was a significant increase in the percentage of
      isolates resistant to erythromycin, clindamycin, ciprofloxacin, gentamicin,
      trimethoprim, and rifampicin (p < 0.001 for each)-resistance characteristics
      often seen in MRSA. Resistance to benzylpenicillin increased slightly but
      significantly (p < 0.001); resistance to fusidic acid was stable (p > 0.05);
      resistance to tetracycline decreased significantly (p < 0.001). INTERPRETATION:
      Among cases of S aureus bacteraemia, the proportion due to MRSA has increased
      significantly. Bacteraemia due to MRSA has a poor prognosis, especially if not
      treated with suitable antibiotics. Therefore, these findings are important,
      especially for management of patients and the development of antibiotic policies.

PMID- 9251637
TI  - Language bias in randomised controlled trials published in English and German.
AB  - BACKGROUND: Some randomised controlled trials (RCTs) done in German-speaking
      Europe are published in international English-language journals and others in
      national German-language journals. We assessed whether authors are more likely to
      report trials with statistically significant results in English than in German.
      METHODS: We studied pairs of RCT reports, matched for first author and time of
      publication, with one report published in German and the other in English. Pairs
      were identified from reports round in a manual search of five leading German
      language journals and from reports published by the same authors in English found
      on Medline. Quality of methods and reporting were assessed with two different
      scales by two investigators who were unaware of authors' identities,
      affiliations, and other characteristics of trial reports. Main study endpoints
      were selected by two investigators who were unaware of trial results. Our main
      outcome was the number of pairs of studies in which the levels of significance
      (shown by p values) were discordant. FINDINGS: 62 eligible pairs of reports were
      identified but 19 (31%) were excluded because they were duplicate publications. A
      further three pairs (5%) were excluded because no p values were given. The
      remaining 40 pairs were analysed. Design characteristics and quality features
      were similar for reports in both languages. Only 35% of German-language articles,
      compared with 62% of English-language articles, reported significant (p < 0.05)
      differences in the main endpoint between study and control groups (p = 0.002 by
      McNemar's test). Logistic regression showed that the only characteristic that
      predicted publication in an English-language journal was a significant result.
      The odds ratio for publication of trials with significant results in English was
      3.75 (95% CI 1.25-11.3). INTERPRETATION: Authors were more likely to publish RCTs
      in an English-language journal if the results were statistically significant.
      English language bias may, therefore, be introduced in reviews and meta-analyses
      if they include only trials reported in English. The effort of the Cochrane
      Collaboration to identify as many controlled trials as possible, through the
      manual search of many medical journals published in different languages will help
      to reduce such bias.

PMID- 9251638
TI  - Cytogenetic effect of chronic low-dose, low-dose-rate gamma-radiation in
      residents of irradiated buildings.
AB  - BACKGROUND: Many people in Taiwan have been living in buildings constructed with
      cobalt-60-contaminated steel rods. To study the biological effects of chronic low
      dose ionising radiation on the residents of one such building, micronucleus
      formation in these individuals was compared with that in controls. METHODS: The
      73 residents had 77 age-and-sex-matched controls: 31 had 31 close relatives as
      controls (group A controls); eight of the 31 had a second set of close relatives;
      and the other controls were 38 residents in neighbouring buildings. Two
      micronucleus assays were used-a cytochalasin B (CBMN) assay and another involving
      incubation with cytarabine (CBMNA). Assay results are given as "frequency", or
      the number of binucleate cells containing one micronucleus per 1000 randomly
      examined binucleate cells. FINDINGS: The CBMN and CBMNA mean (SD) frequencies for
      31 exposed individuals (0.016 [0.009] and 0.025 [0.013] respectively) were
      greater than those for their group A controls (0.009 [0.004] and 0.016 [0.009],
      respectively) (p = 0.0006 and 0.0002, respectively). The mean CBMN and CBMNA
      frequencies for all the exposed individuals (0.017 [0.011] and 0.030 [0.014],
      respectively) were significantly greater than those for all controls (0.011
      [0.008] and 0.019 [0.01]; p = 0.0001 for both comparisons). The ranges of the
      differences in CBMN or CBMNA frequencies between 31 exposed individuals and their
      group A controls were 0.003 to 0.020 and 0.001 to 0.032, respectively. After
      adjustment for age, sex, and cigarette smoking, the adjusted relative risks of
      micronucleus formation from radiation exposure in all 73 residents was 1.58 (95%
      CI 1.42-1.71; p = 0.0001) by the CBMN assay and 1.64 (1.53-1.77; p = 0.0001) by
      the CBMNA assay. INTERPRETATION: These findings suggest that chronic low-dose and
      low-dose-rate gamma-ray environmental exposure may induce cytogenetic damage in
      human beings.

PMID- 9251639
TI  - A pain in the groin.

PMID- 9251640
TI  - Thrombospondin-related adhesive protein (TRAP) of Plasmodium berghei and parasite
      motility.

PMID- 9251641
TI  - Subretinal haemorrhage after granulocyte colony-stimulating factor.

PMID- 9251642
TI  - Presenilin-I, presenilin-II, and VLDL-R associations in early onset Alzheimer's
      disease.

PMID- 9251643
TI  - Autologous bone-marrow transplantation for rheumatoid arthritis.

PMID- 9251644
TI  - Chronic progressive leptomeningitis associated with measles virus.

PMID- 9251645
TI  - Anophthalmia and agenesis of optic chiasma associated with adapalene gel in early
      pregnancy.

PMID- 9251646
TI  - Neural innervation and healing.

PMID- 9251647
TI  - Antibiotic prophylaxis after swan bite.

PMID- 9251648
TI  - Aberrant internal carotid artery in the mouth.

PMID- 9251649
TI  - Psoriasis.

PMID- 9251650
TI  - Interventional radiology.
AB  - One of the most interesting things about interventional radiology is how
      techniques have been borrowed from other areas. The lateral thinking which
      characterises this new specialty has allowed it to flourish even while it has
      lost "turf" to other specialties. Inevitably, primary referral to interventional
      radiologists will happen in the same way as referral to, say, surgeons or
      cardiologists dose already. Those who administer health funds and medical
      education will need to adjust to this new situation. This article provides
      examples of many treatment tasks that the interventional radiologist now tackles.

PMID- 9251651
TI  - Severity of malaria and level of Plasmodium falciparum transmission.

PMID- 9251652
TI  - Severity of malaria and level of Plasmodium falciparum transmission.

PMID- 9251653
TI  - Severity of malaria and level of Plasmodium falciparum transmission.

PMID- 9251654
TI  - Severity of malaria and level of Plasmodium falciparum transmission.

PMID- 9251655
TI  - Severe hepatitis in patients with AIDS and haemophilia B treated with indinavir.

PMID- 9251656
TI  - Primary hyperparathyroidism.

PMID- 9251657
TI  - Primary hyperparathyroidism.

PMID- 9251658
TI  - Breast cancer genetics.

PMID- 9251660
TI  - Breast cancer genetics.

PMID- 9251659
TI  - Breast cancer genetics.

PMID- 9251661
TI  - AIRE Extension (AIREX) Study.

PMID- 9251662
TI  - AIRE Extension (AIREX) Study.

PMID- 9251663
TI  - Autoimmune (idiopathic) thrombocytopenic purpura.

PMID- 9251664
TI  - Autoimmune (idiopathic) thrombocytopenic purpura.

PMID- 9251665
TI  - Leishmaniasis mimicking collagen disease.

PMID- 9251666
TI  - Growth factors in saliva.

PMID- 9251667
TI  - Polymorphism of alpha-adducin and hypertension.

PMID- 9251668
TI  - Good manners for the pharmaceutical industry.

PMID- 9251669
TI  - Good manners for the pharmaceutical industry.

PMID- 9251670
TI  - Good manners for the pharmaceutical industry.

PMID- 9251671
TI  - Good manners for the pharmaceutical industry.

PMID- 9251672
TI  - Health impact of human rights violations in Haitian refugees.

PMID- 9251673
TI  - Organ transplant waiting-list in France.

PMID- 9251674
TI  - Pathobiology of the heart in experimental diabetes: immunolocalization of
      lipoproteins, immunoglobulin G, and advanced glycation endproducts proteins in
      diabetic and/or hyperlipidemic hamster.
AB  - Diabetes is known to be accompanied by atherosclerotic disease and general
      cardiovascular complications. Hamsters were previously shown to develop
      hyperlipemia-induced atherosclerosis, similar in many respects to the human
      atherosclerotic process. To study the effect of hyperglycemia on heart vessels
      and valves, male Golden Syrian hamsters were rendered either diabetic or
      hyperlipemic and diabetic; controls were age-matched normal hamsters. At time
      intervals ranging from 2 to 24 weeks, animals were killed; plasma glucose,
      cholesterol, and lipid peroxides were measured; and the aortic arch and valves,
      coronary arteries, and heart microvessels were examined for ultrastructural
      modifications and for the presence of low-density lipoproteins (LDL),
      immunoglobulin G (IgG), and advanced glycation endproducts (AGE) proteins.
      Elevation of plasma glucose, peroxides, and cholesterol were observed in both
      diabetic as well as hyperlipemic and diabetic animals, along with characteristic
      diabetic changes: microangiopathy of the myocardium (ie, capillary narrowing,
      hyperplasia of basal lamina, and proliferation of extracellular matrix) and
      macroangiopathy of the aortic arch, valves, and coronary arteries (ie, intimal
      proliferation, fatty-streak formation, and calcification). LDL, IgG, and AGE
      proteins were immunolocalized in focal deposits, ie, in the shoulder and cap of
      the plaques; these antigens were distributed diffusely in the extracellular space
      or within macrophage-derived foam cells and smooth muscle cells. Our findings
      indicate that hyperglycemia alone induces atherosclerotic lesions in the coronary
      arteries, aortic arch, and aortic valves as well as alterations of the
      extracellular matrix of heart microvessels and cardiomyocytes, changes which
      together may lead to cardiomyopathy, a common and severe complication of
      diabetes. In addition, the present study suggests that when hyperglycemia is
      accompanied by hyperlipemia, detectable amounts of modified LDL (possibly
      oxidized or glycated) and AGE are present in the intima of atherosclerotic
      arteries; and also that modified lipoproteins can act as immunoactive components
      of the atheroscerotic process generated by hyperglycemia.

PMID- 9251675
TI  - Blocking of alpha 1 beta 1 integrin strongly improves survival of hepatocytes in
      allogeneic transplantation.
AB  - The survival rate of hepatocytes after allogeneic hepatocyte transplatation (HTX)
      is low, possibly because of formation of intravascular hepatocyte aggregates. The
      aim of this study was to determine the role of integrins in intravascular
      aggregation and intraparenchymal survival of transplanted hepatocytes in a fully
      allogeneic rat model. First, the expression profile of various integrins was
      determined on both isolated hepatocytes in vitro and on hepatocyte aggregates in
      recipient livers after intraportal transplantation of allogeneic hepatocytes.
      Next, the role of these integrins in hepatocyte aggregation was determined in an
      in vitro attachment assay on liver sections with function-blocking anti-integrin
      monoclonal antibodies (mAb). The results showed that anti-alpha 1 beta 1 integrin
      mAb significantly block hepatocyte attachment to vessel walls and liver
      parenchyma in vitro. Subsequently, the effect of preincubation of hepatocytes
      with anti-integrin mAb on their intravascular aggregation and on intraparenchymal
      survival was studied in an allogeneic HTX model. Preincubation with anti
      leukocyte function-associated antigen-1 alpha or anti-beta 2 mAb significantly
      intravascular hepatocyte aggregation, and anti-leukocyte function-associated
      antigen-1 alpha mAb enhanced intraparenchymal survival. Preincubation with anti
      alpha 1 or anti-beta 1 mAb did not inhibit aggregation but significantly improved
      survival from 2% to up to 45% at Day 2 after transplantation (p < 0.001). In
      conclusion, our results suggest that the blocking of alpha 1 beta 1 integrin
      significantly improves survival of allotransplanted hepatocytes.

PMID- 9251676
TI  - Presence of inducible nitric oxide synthase, nitrotyrosine, CD68, and CD14 in the
      small intestine in celiac disease.
AB  - Celiac disease is characterized by severe inflammation of the small intestine,
      and inflammation is known to often be associated with enhanced nitric oxide (NO)
      production. The aim of the present study was to determine whether children with
      active celiac disease show increased duodenal inducible nitric oxide synthase
      (iNOS) expression by immunohistochemistry. For this purpose, NO activity was
      assessed by detection of nitrotyrosine, which is an indicative marker for the
      formation of the NO- and superoxide-derived oxidant peroxynitrite. Serial
      staining with the macrophage markers CD68 and CD14 was performed to assess
      whether intestinal macrophages are involved in intestinal NO production. Duodenal
      biopsies from seven children with normal biopsy findings were used for
      comparison. Intense iNOS staining of enterocytes was observed in 10 of 11 celiac
      disease biopsies but in only 1 of 7 controls (p < 0.002). In addition,
      nitrotyrosine staining was detected in the enterocytes of celiac disease patients
      and was associated with iNOS staining. Moreover, the number of iNOS-positive
      cells in the lamina propria was significantly (p < 0.002) enhanced in patients
      with celiac disease. Serial staining for iNOS, CD68, and CD14 revealed an
      increase in CD68/CD14 double-positive monocytes and colocalization of iNOS and
      CD14 expression associated with this disease. Collectively, these data suggest
      that in patients with active celiac disease, synthesis of iNOS is induced in the
      intestine in association with the formation of peroxynitrite and nitration of
      cellular proteins. Furthermore, the increase in intestinal CD14-positive
      macrophages suggests a role for these cells in the pathophysiology of the
      disease.

PMID- 9251677
TI  - Distribution and colocalization of calcitonin gene-related peptide, tachykinins,
      and vasoactive intestinal peptide in normal and idiopathic unstable human urinary
      bladder.
AB  - The distribution of nerves containing calcitonin gene-related peptide (CGRP),
      substance P (SP), neurokinin A (NKA), and vasoactive intestinal peptide (VIP) was
      examined in the human urinary bladder, using both single- and double-label
      immunohistochemistry. Nerves containing CGRP and tachykinins were typically
      present within the subepithelial region, encircling intramural ganglia and around
      blood vessels. These nerves were sparsely distributed, and only very rarely
      projected to the smooth muscle bundles of the detrusor. In contrast, VIP
      containing nerves formed a dense subepithelial plexus and also projected to the
      detrusor muscle bundles. The double-label studies revealed that approximately 26%
      +/- 10% of CGRP-immunoreactive nerves also contained SP and NKA, but that no CGRP
      fibers coexpressed VIP. Conversely, all SP-immunoreactive fibers also contained
      CGRP, and many coexpressed NKA. At least three neurochemically distinct
      populations of nerves can therefore be discerned in the human bladder: VIP/-,
      CGRP/-, and CGRP/SP/ +/- NKA. The density of CGRP and SP-immunoreactive nerves
      within the subepithelium of 14 women with urodynamically-proven idiopathic
      detrusor instability was increased by 82% (p = 0.003) and 94% (p = 0.036),
      respectively, relative to that of 14 control women with no symptoms of frequency
      or urgency. This effect was not due to an increase in overall nerve density,
      because immunoreactivity for the general nerve marker, protein gene product, was
      not significantly different between the two groups (p = 0.21). The results
      indicate that at least some patients with detrusor instability demonstrate
      increases in a specific class of nerve fibers containing CGRP and SP. These
      peptides are characteristic of sensory neurons in a number of species, suggesting
      that abnormalities in the afferent arm of the micturition reflex may be
      associated with detrusor instability.

PMID- 9251678
TI  - Thrombospondin-1 suppresses tumorigenesis and angiogenesis in serum- and
      anchorage-independent NIH 3T3 cells.
AB  - Thrombospondin-1 (TSP1) is a multifunctional matrix protein that influences the
      growth and function of a variety of normal and neoplastic epithelial and
      mesenchymal cell types. In vivo, TSP1 has shown potent antitumor activity in
      suppressing tumor neovascularization. Paradoxically, however, as we have
      reported, NIH 3T3 fibroblasts overexpressing TSP1 acquire the transformation
      associated phenotypes of serum and anchorage independence in vitro but fail to
      form tumors in nude mice. To investigate these divergent results, and to
      determine the functional domains in TSP1 that confer serum and anchorage
      independence as well as antitumor and antiangiogenic activities, we transfected a
      series of deletion constructs of TSP1 into NIH 3T3 cells and into a v-src
      transformed NIH 3T3 line. The antiangiogenic activity of TSP1-expressing, v-src
      transformed NIH 3T3 cells was examined by assaying the conditioned media for
      inhibition of endothelial cell chemotaxis and suppression of basic fibroblast
      growth factor-mediated angiogenesis in the rat cornea. The link between TSP1
      antitumor and antiangiogenic activities was assessed by measuring the rate of
      tumor growth and counting factor VIII-stained microvessels in the solid tumors
      developing in nude mice. Our results indicate that v-src NIH 3T3 cells
      transfected with a 449-amino acid N-terminal domain of TSP1 exhibit a dose
      dependent suppression of tumor growth and neovascularization in nude mice.
      Truncated forms of TSP1 containing the type 1 properdin domain suppressed both
      endothelial cell chemotaxis and comeal neovascularization. Furthermore, when full
      length TSP1 and deletion constructs containing the antiangiogenic type I
      properdin domain were transfected into highly tumorigenic v-src-transformed NIH
      3T3 cells, they were able to confer transdominant suppression of tumorigenicity
      and angiogenesis of these cells in nude mice. These results confirm the role of
      TSP1 as a potent inhibitor of angiogenesis and provide support for the notion
      that alterations in the net balance between inducers and inhibitors of
      angiogenesis are largely responsible for the sustained growth of solid tumors in
      vivo.

PMID- 9251679
TI  - Characterization of a new human liver myofibroblast cell line: transcriptional
      regulation of plasminogen activator inhibitor type I by transforming growth
      factor beta 1.
AB  - Myofibroblasts (MF) are a major effector cell type in liver fibrogenesis, where
      they are thought to derive from the activation of hepatic stellate cells.
      Cultured human MF, grown from liver explants, retain most of the in vivo
      characteristics of liver MF but are in limited supply. A continuous MF cell line
      would therefore be valuable in studying human liver fibrogenesis. For this
      purpose, we sought to immortalize human liver MF with polyoma virus large T
      antigen. MF were obtained from explants of human liver and transfected with a
      plasmid containing the coding sequence of polyoma virus large T antigen. This
      procedure yielded an activity growing cell line, designated GREF-X, which did not
      express large T antigen. Nevertheless, this cell line has been passaged
      repeatedly for almost 1 year and is thus likely immortalized. The morphology of
      GREF-X resembles that of primary liver MF. These cells have a doubling time of
      approximately 72 hours and are density-inhibited, and their growth is serum
      dependent. Moreover, GREF-X cells do not grow in soft agar or induce tumors in
      nude mice, suggesting that they are not transformed. They stain positively for MF
      markers, such as smooth muscle alpha-actin and vimentin; express collagens type
      I, IV, V, and VI, fibronectin, and laminin: and secrete matrix-metalloproteinase
      2. In addition, GREF-X cells are able to take up and esterify [3H]retinol,
      suggesting that they actually derive from hepatic stellate cells. Finally, these
      cells respond to transforming growth factor-beta 1, a major mediator of liver
      fibrogenesis, by increasing secretion of fibronectin and plasminogen activator
      inhibitor type 1. Transient transfection experiments showed that plasminogen
      activator-inhibitor type 1 regulation, by transforming growth factor-beta 1, was
      transcriptional. We believe, therefore, that GREF-X would be a useful tool for
      studying the pathophysiology and pharmacology of liver fibrogenesis.

PMID- 9251680
TI  - Interferon alpha/beta mediates early virus-induced expression of H-2D and H-2K in
      the central nervous system.
AB  - Cells of the central nervous system (CNS) normally do not express detectable
      levels of major histocompatibility complex (MHC) Class I antigens. However, MHC
      Class I expression can be induced after virus infection. We tested the hypothesis
      that virus-induced Class I expression is mediated by lymphocytes or cytokines
      using lymphocyte- and cytokine-deficient mice. We used Theiler's murine
      encephalomyelitis virus (TMEV), which induces CNS demyelination that maps
      genetically to the D region of MHC Class I and is associated with high levels of
      Class I products. TMEV infection of severe combined immunodeficiency (SCID) and
      recombination activation gene-1-deficient mice, which lack B and T lymphocytes,
      resulted in equivalent H-2D and H-2K expression in brain and spinal cord,
      according to analysis of the area and intensity of immunoperoxidase staining.
      Class I antigens were demonstrated as early as 6 hours after infection, and they
      were more widely distributed than viral RNA, indicating that expression was
      induced indirectly via a soluble factor. To determine whether cytokines induced
      the expression, we infected mice lacking receptors for interferon-alpha/beta (IFN
      alpha/beta R (-/-)), interferon-gamma (IFN-gamma R(-/-)), and tumor necrosis
      factor-alpha (TNFRp55(-/-)). TMEV-infected IFN-gamma R(-/-) and TN-FRp55(-/-)
      mice expressed Class I antigens in the CNS, whereas IFN-alpha/beta R(-/-) mice
      did not, establishing that IFN-alpha/beta mediated the expression. In contrast to
      the equivalent expression in SCID mice, we observed greater area and higher
      intensity of H-2D versus H-2K antigens in infected SCID mice reconstituted with
      normal spleen cells. Collectively, the data indicate that after TMEV infection,
      early generalized MHC Class I expression is mediated by IFN-alpha/beta
      independently of lymphocytes, but the differential regulation of H-2D over H-2K
      may be controlled by B and/or T lymphocytes.

PMID- 9251681
TI  - A novel gene which is up-regulated during colon epithelial cell differentiation
      and down-regulated in colorectal neoplasms.
AB  - To identify new molecular markers for differentiation of normal and neoplastic
      colon epithelium, we have studied changes in gene expression during the in vitro
      differentiation of the HT29-D4 colon carcinoma cell line. Using a modified
      differential display procedure, we cloned a novel cDNA, designated
      differentiation-related gene 1 (Drg1). Drg1 mRNA has a length of approximately 3
      kb and is induced approximately 20-fold during in vitro differentiation of the
      colon carcinoma cell lines HT29-D4 and Caco-2. The absence of Drg1 induction in
      growth-inhibited A431 epidermoid carcinoma cells indicates that Drg1 up
      regulation in colon carcinoma cells is not a result of decreased proliferation.
      The Drg1 cDNA contains an open-reading frame of 1182 bp that encodes a protein
      with a predicted molecular weight of 43 kd. Drg1 mRNA is expressed most
      prominently in placental membranes and prostate, kidney, small intestine, and
      ovary tissues. Compared to normal colon mucosa, Drg1 mRNA expression is decreased
      in colon adenomas and adenocarcinomas. An antiserum raised against recombinant
      Drg1 protein detected a band of the expected size in Western blots.
      Immunohistochemistry showed that in normal colon Drg1 protein is expressed in the
      cytoplasm and basolateral membranes of surface epithelial cells that border the
      gut lumen, indicating that Drg1 protein is expressed late during differentiation,
      just before apoptosis and shedding of cells into the colon lumen.

PMID- 9251682
TI  - Expression of caveolae on the surface of rat arterial smooth muscle cells is
      dependent on the phenotypic state of the cells.
AB  - Both after vascular injury and when established in vitro, arterial smooth muscle
      cells pass through a characteristic change in phenotype. This process includes a
      prominent structural reorganization with partial loss of myofilaments and
      formation of a large endoplasmic reticulum and Golgi complex. As a result, the
      cells lose their contractility and become able instead to divide and to secrete
      extracellular matrix components. In the present study, the expression of plasma
      membrane caveolae in rat arterial smooth muscle cells was studied in primary
      culture and during the formation of neointimal thickenings after balloon injury.
      Electron microscopic analysis revealed that the number of caveolae (identified as
      flask-shaped invaginations of the plasma membrane) was reduced when the cells
      converted from a contractile to a synthetic phenotype (as defined
      morphologically) and then increased again when they readopted a more
      differentiated state. However, immunoblotting analysis did not show any changes
      in the cellular content of caveolin (a major protein component of caveolae)
      during the 1st week in culture. At the same time, immunocytochemical staining
      demonstrated a shift in the localization of caveolin from small spot-like
      structures dispersed over the cell surface to vesicular structures in the
      perinuclear cytoplasm. These findings indicate that the transition of smooth
      muscle cells from a contractile to a synthetic phenotype involves a marked
      decline in the number of plasma membrane caveolae. In parallel, caveolin is
      internalized and redistributed to Golgi-associated vesicles in the perinuclear
      cytoplasm. In context of the rapidly increasing awareness of the importance of
      caveolae both in signal transduction and intracellular cholesterol transport, it
      seems likely that the variations in the number of caveolae may be significant for
      the functional differences between smooth muscle cells in different phenotypes.

PMID- 9251683
TI  - Osteopontin is strongly expressed by histiocytes in granulomas of diverse
      etiology.
AB  - Granulomatous inflammation is associated with a variety of important pathologic
      conditions. Osteopontin (OPN), a ligand for the alpha v beta 3 integrin, is a
      secreted glycoprotein with a glycine-arginine-glycine-aspartate-serine cell
      binding domain. In this study, we examined expression of OPN in 22 cases of
      granulomatous inflammation including cases of sarcoidosis, granulomatous temporal
      arteritis, histoplasmosis, rheumatoid nodule, granuloma annulare, erythema
      nodosum, granulomatous gastritis, foreign body giant-cell granulomatous
      reactions, and lipogranulomas. Strong expression of OPN mRNA and protein was seen
      in the epithelioid histiocytes and multinucleate histiocytic giant cells in
      granulomas by in situ hybridization and immunostaining. OPN may play an important
      role in granulomatous inflammation through the regulation of processes such as
      histiocyte migration, cell adhesion, and cellular functions including
      phagocytosis.

PMID- 9251685
TI  - Victorian orphans and clinical research.

PMID- 9251684
TI  - A new single-injury model of balloon angioplasty in cholesterol-fed rabbits:
      beneficial effect of hirudin and comparison with double-injury model.
AB  - Air desiccation endothelial injury followed by cholesterol feeding is known to
      induce focal femoral atherosclerosis in rabbits. We previously demonstrated the
      effectiveness of hirudin in limiting restenosis after balloon angioplasty (BA) in
      this double instrumentation injury (DI) model. In the present study, we sought to
      determine whether BA without prior air desiccation endothelial injury (single
      instrumentation injury (SI)) would lead to similar femoral lesions, and whether
      the response to this injury might also be limited by hirudin. Accordingly, 38
      femoral arteries of cholesterol-fed rabbits underwent BA with (n = 18, DI group)
      or without (n = 20, SI group) prior air desiccation endothelial injury. Animals
      were killed 24 hours or 28 days after BA. Twenty-four hours after BA, the SI
      group (n = 10) had a significantly smaller percentage of cross-sectional area
      narrowing by plaque than the DI group (n = 8) (0% versus 42% +/- 9%, p = 0.008).
      However, 28 days after BA, the percentages of cross-sectional area narrowing by
      plaque in the SI (n = 10) and DI (n = 10) groups were similar (59% +/- 6% versus
      68% +/- 1%, p = NS). The percentages of intima (16% +/- 3% versus 16% +/- 3%, p =
      NS) and media occupied by foam cells were also similar in the two groups. To test
      whether hirudin administration would limit arterial narrowing after injury in the
      SI model, we randomly assigned cholesterol-fed rabbits that had not undergone air
      desiccation injury to either bolus hirudin followed by repeat dosing 24 hours
      after BA or bolus heparin (150 U/kg) at the time of BA. The hirudin-treated group
      showed significantly less angiographic and histologic restenosis 28 days after
      BA, despite no difference in early (0 to 72 hours) cumulative cellular
      proliferation between the two groups. Thus, in the cholesterol-fed rabbit, plaque
      formation and foam cell accumulation are similar after BA of a non-air-desiccated
      (SI) or focally atherosclerotic (DI) artery. Thrombin inhibition with hirudin
      limits arterial narrowing after SI, further emphasizing the role of thrombin in
      neointimal growth after injury.

PMID- 9251686
TI  - Reducing the burden of chronic heart failure.

PMID- 9251687
TI  - Urinary symptoms as men age: the reassurance of an evidence-based approach.

PMID- 9251688
TI  - Barriers to quality in general practice.

PMID- 9251689
TI  - Diabetes: the light at the end of the tunnel looks brighter.

PMID- 9251690
TI  - Burden and outcomes of hospitalisation for congestive heart failure.
AB  - OBJECTIVE: To describe the hospital burden and health outcomes associated with
      admission for congestive heart failure (CHF). DESIGN AND SETTING: Descriptive
      follow-up study in a tertiary-level metropolitan teaching hospital. PATIENTS:
      Acute adult inpatients with a clinical diagnosis of CHF for more than 24 hours
      admitted to Westmead Hospital, Sydney, during the four months from September 1993
      to January 1994. At baseline, 122 patients were assessed; 88 patients were
      assessed at four-month follow-up. INTERVENTIONS: Usual clinical care. MAIN
      OUTCOME MEASURES: Length of stay; hospital bed-days; readmissions; mortality;
      health related quality of life (SF-36); patient knowledge. RESULTS: The average
      age of subjects was 73.4 years. Many were using informal domiciliary care before
      admission. Mean length of stay for the baseline admission was 13.8 days,
      accounting for 7.6% of hospital separations and 1683 hospital bed-days, or 4.2%
      of bed-days for all inpatients aged 65 years and over. Fifteen patients were
      readmitted for CHF during the following four months, with a total of 26 CHF
      related admissions. Twenty-one patients (17.2%) died during the course of the
      study. Quality of life at baseline was poor compared with population normative
      data, with a slight improvement among survivors at four-month follow-up. Patient
      knowledge of CHF was poor in a subsample survey (n = 24). CONCLUSIONS: CHF
      represents a significant burden to patients (through morbidity and mortality),
      their carers (through provision of daily care), and hospitals (through multiple
      admissions for acute decompensation). It is difficult to monitor the hospital
      burden of CHF using routine data sources.

PMID- 9251691
TI  - Troublesome lower urinary tract symptoms in the community: a prevalence study.
AB  - OBJECTIVE: To determine the prevalence of troublesome lower urinary tract
      symptoms (LUTS) in men and women in the community. DESIGN: Interview-based
      prevalence survey. SETTING: Metropolitan and rural communities in South
      Australia, September, 1995. SUBJECTS: Probability sample of 1204 men and 1686
      women (aged over 18 years) weighted to reflect the age and sex distribution of
      the South Australian population. DATA COLLECTED: Presence of storage (irritative)
      and voiding (obstructive) symptoms, based on the International Prostate Symptom
      Score questionnaire; satisfaction with urinary condition (quality-of-life
      measure); and visits to a doctor for urinary symptoms in the preceding 12 months.
      RESULTS: The prevalence of one or more troublesome LUTS was 26% (318/1204) for
      men and 39% (662/1686) for women (all ages) and 48% (314/649) for men and women
      over 65. The most common troublesome symptoms in men and women were nocturia and
      frequency. Symptoms were significantly age-related in men, but less so in women,
      in whom symptom prevalence exceeded 30% for all age groups. Ten per cent of men
      (123/1204) and 15% of women (249/1686) had visited a doctor for a urinary problem
      in the previous 12 months. Nine per cent of men (104/1204) and 16% of women
      (274/1686) were substantially dissatisfied with their urinary condition. Symptom
      prevalence and dissatisfaction with urinary condition were significantly
      associated with visiting the doctor (P < 0.0001), but only 28% (88/318) of men
      and 27% (179/662) of women with troublesome LUTS saw a doctor, and 63% (65/104)
      of men and 59% (162/274) of women dissatisfied with their urinary condition did
      not seek medical help. CONCLUSIONS: Although the prevalence of troublesome LUTS
      in the community is high, the number of people whose quality of life is
      substantially affected is much lower. The impact of these symptoms upon quality
      of life is a major reason for patients to see a doctor, yet many who are
      "bothered" by the symptoms do not do so.

PMID- 9251692
TI  - Characteristics of longer consultations in Australian general practice.
AB  - OBJECTIVE: To assess the association between general practitioner (GP) billing
      for "longer" consultations, patient factors linked with health care need, and
      other consultation characteristics. DESIGN: Retrospective analysis of data from
      Medicare (1984-1992), Australian Morbidity and Treatment Survey (1990-1991) and
      Australian Capital Territory Record Linkage Study (1988-1992). SETTING:
      Australian general practice, 1984 (introduction of Medicare) to 1992. MAIN
      OUTCOME MEASURES: Consultations billed as longer (> or = 20 or > 25 minutes)
      compared with standard; type of billing (bulk or private); patient health care
      need (defined as health and sociodemographic factors linked to worse health
      outcomes); consultation continuity, type of care given and number of problems
      managed. RESULTS: Longer billed consultations increased between 1984 and 1992,
      from 2.8% to 6.7% of all standard and longer consultations. Longer consultations
      were more likely to be bulk-billed than privately billed (odds ratio [OR], 1.74).
      They were more likely than standard consultations to deal with psychological
      diagnoses (OR, 2.06; 95% confidence interval [95% Cl], 1.83-2.32) or multiple
      problems (OR for four versus one diagnosis, 5.18; 95% Cl, 4.31-6.22) and to
      involve patients aged under 50 years, new to the practice or with new problems,
      but not chronic disease. In the ACT, those billed for longer consultations were
      more commonly tertiary educated (OR, 1.99; 95% Cl, 1.35-2.94), bulk-billed (OR,
      2.75; 95% Cl, 2.51-3.10), aged 40-49 years and non-obese. CONCLUSION: Longer
      billed consultations were not associated with greater patient need, other than
      psychosocial need, but with bulk billing and patient socioeconomic advantage.
      However, evaluation was complicated by the effects of continuity of care and
      number of problems managed in the consultation.

PMID- 9251693
TI  - Fatal granulomatous amoebic encephalitis caused by Balamuthia mandrillaris.
AB  - Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris is rare (63
      human) cases reported worldwide) and fatal. We report a case in a five-year-old
      boy who had previously been well. For 18 months, he had had a slowly progressive,
      granulomatous mid facial lesion, but despite extensive investigation definitive
      diagnosis was made only with the acute onset of neurological signs in the last
      two weeks of life, when a brain biopsy specimen revealed amoebic trophozoites and
      cysts. Infection with B. mandrillaris should be considered in the differential
      diagnosis of chronic skin lesions with non-specific granulomatous histopathology
      and negative microbiological test results.

PMID- 9251694
TI  - Haemorrhoids: a clinical update.
AB  - Haemorrhoids are common, but careful clinical assessment is necessary to ensure
      that more significant bowel disease is not overlooked. Most patients with
      haemorrhoids can be managed non-surgically in an office setting, but conventional
      haemorrhoidectomy is the best option for patients with large symptomatic
      haemorrhoids.

PMID- 9251695
TI  - Trials of providing costing information to general practitioners: a systematic
      review.
AB  - OBJECTIVE: To determine if providing general practitioners (GPs) with costing
      information can change their clinical behaviour and reduce medical costs. DATA
      SOURCES: MEDLINE, CINAHL, Health Plan and EMBASE and citations in review articles
      were searched for studies published between 1980 and 1996. STUDY SELECTION:
      Studies were included if they provided costing information to GPs with the aim of
      decreasing costs by changing behaviour, included an objective measure of GP
      performance or clinical care, and used a randomised or quasi-randomised
      controlled design, crossover design or a controlled time series. DATA EXTRACTION:
      Data extracted included study design, intervention used and measure of GP
      performance/clinical care (including test ordering, drug prescribing, hospital
      and primary care visits and costs). DATA SYNTHESIS: Six studies met the inclusion
      criteria. Computerised feedback on drug costs increased generic prescribing, and
      "academic detailing" decreased inappropriate prescribing of target drugs.
      Providing costing information also decreased ordering of diagnostic tests.
      "Gatekeeper" physicians reduced use of hospital and specialist services. Only two
      studies found the changes were sustained for nine months or longer and only one
      evaluated health outcomes. CONCLUSION: The provision of costing information can
      change GP behaviour in all service areas. Sustainability of these changes and
      linking of cost savings to health outcomes have not been well studied.

PMID- 9251696
TI  - Glycohaemoglobin: a crucial measurement in modern diabetes management. Progress
      towards standardisation and improved precision of measurement. Australian
      Diabetes Society, the Royal College of Pathologists of Australasia and the
      Australasian Association of Clinical Biochemists [consensus development
      conference].
AB  - There are currently four principal glycohaemoglobin assay techniques (ion
      exchange chromatography, electrophoresis, affinity chromatography and
      immunoassay) and about 20 different methods that measure different glycated
      products and report different units. Standardisation will lead to all assays
      reporting results in a standard unit, the HbA1c percentage of total serum
      haemoglobin, and should be in place within the next one to three years. In the
      interim, clinicians using glycohaemoglobin assays should be aware that the ranges
      indicating good and poor glycaemic control can vary markedly between different
      assays. The reproducibility of some assays may be insufficient to provide
      definitive evidence of changes in glycaemic control. Some assays may be so
      imprecise that they are unable to separate patients with good and poor control.
      INTERIM RECOMMENDATIONS 1 The terminology to be used for the assay is
      glycohaemoglobin (GHb) assay (recommendation from the combined meetings of the
      International Federation of Clinical Chemistry [IFCC] Working Group on HbA1c
      standardisation and the American Association of Clinical Chemistry [AACC]
      Subcommittee on Glycohemoglobin). 2 The unit of measurement for GHb assays should
      be reported as %HbA1c (Diabetes Control and Complications Trial equivalent). 3
      Other units, such as % total GHb or %HbA1, should not be used. Assays producing
      these units should be converted to %HbA1c reporting units. 4 Assays with high
      precision are highly desirable. The IFCC/AACC are currently recommending between
      run coefficients of variation of less than 5% for manufacturers of kits and
      instruments. However, between-run coefficients of variation of less than 3% are
      far more clinically useful and therefore desirable.

PMID- 9251697
TI  - Lung cancer.
AB  - Lung cancer needs to be considered in patients with a history of cigarette
      smoking and/or symptoms such as haemoptysis or non-resolving cough. Radiological
      investigations are useful in staging, but a tissue diagnosis is necessary to
      confirm the presence of a tumour. Although early detection and referral are
      important to achieve the best chance of a cure, primary prevention by smoking
      cessation is the most important measure.

PMID- 9251698
TI  - Heroin-related deaths in south-western Sydney.

PMID- 9251699
TI  - Rates of membership of professional organisations in general practice.

PMID- 9251700
TI  - Sexually transmitted diseases: we must commit to contact tracing.

PMID- 9251701
TI  - "On-the-spot" vaccination.

PMID- 9251702
TI  - Ecstasy, serotonin syndrome and the treatment of hyperpyrexia.

PMID- 9251703
TI  - Adverse reactions to digoxin in four patients with normal or low serum digoxin
      levels.

PMID- 9251704
TI  - An intractable error in MEDLINE.

PMID- 9251705
TI  - The musculoskeletal sequelae of participation in the Vietnam War.

PMID- 9251706
TI  - Time for action and education: women, HIV and babies.

PMID- 9251707
TI  - Housing and sudden infant death syndrome. The New Zealand Cot Death Study Group.
AB  - AIMS: This paper examined factors relating to the infants' place of domicile to
      see whether they increased the risk of sudden infant death syndrome (SIDS) beyond
      social and environmental effects previously published. METHODS: A case control
      study was undertaken in New Zealand between the years 1987-90. From all sudden
      infant death syndrome diagnoses over this time, parents of 393 (81%) sudden
      infant death syndrome infants consented to participate and these derive the
      cases. Controls were ascertained by randomly sampling 1800 infants from all
      babies born over 78% of the country. Parents of 1592 (88%) control infants
      consented to participate in the study. RESULTS: The relative risk of sudden
      infant death for infants usually residing in houses rented from the government
      (State houses) was 1.73 (95% CI: 1.13, 2.66) times that of infants with parents
      owning their house, after adjusting for likely social, economic and environmental
      confounding factors. However, the type of housing, construction of housing,
      heating and age of housing was not associated with sudden infant death syndrome.
      Although house size, measured in terms of bedroom numbers, was similar for sudden
      infant death syndrome and control infants (chi 2 = 0.40, df = 2, p = 0.82), the
      number of people normally residing within these houses was different. Sudden
      infant death syndrome infants' houses were less likely to have two adults and
      more likely to have more children normally resident. Density calculations
      (derived by calculating the children and/or adult numbers divided by bedroom
      numbers) revealed a non significant increase in relative risk, suggesting that
      housing overcrowding was not associated with sudden infant death syndrome in New
      Zealand. CONCLUSIONS: Infants domiciled in State houses are more likely to
      experience sudden infant death syndrome. However, this increased relative risk
      for sudden infant death syndrome appears to have little to do with the house per
      se and, perhaps, more to do with socioeconomic characteristics.

PMID- 9251708
TI  - Occupational asthma and other nonasbestos occupational respiratory diseases
      notified between 1993 and 1996.
AB  - AIM: To review notifications to the Occupational Safety and Health Service of the
      Department of Labour Notifiable Occupational Disease System since its inception
      until June 1996. METHODS: All notifications received for non asbestos related
      occupational respiratory disease were reviewed to evaluate the outcome of the
      notification and to identify the causative agent where possible. RESULTS: There
      were 277 cases notified and investigated including worksite investigations. Of
      these 73 cases were confirmed as having occupational asthma, 35 by the asthma
      validation panel. Nineteen cases of other occupational respiratory disease were
      notified of which 11 were reviewed by the panel. Extrinsic allergic alveolitis
      secondary to organic dusts was the most common such notification. CONCLUSIONS:
      Isocyanates are well recognised as a cause of occupational asthma in New Zealand.
      It is suspected that occupational asthma and other occupational respiratory
      diseases are poorly notified to this system. Better mechanisms are needed to
      identify occupational causes of respiratory (and other) disease.

PMID- 9251709
TI  - Remanipulation of forearm fractures in children.
AB  - AIMS: To determine whether operator experience or time of operation affects the
      outcome of fractures of the forearm in the paediatric age group as measured by
      the need for remanipulation. METHODS: A retrospective analysis of 1155 children
      with forearm fractures requiring manipulation was undertaken. RESULTS: The
      remanipulation rate for these 1155 children was 136 or 11.7%. There was a
      significant difference in those fractures requiring remanipulation dependent upon
      the experience of the operator and the time of day the procedure was performed.
      The lowest rate of remanipulation was obtained by senior registrars operating
      between the hours of 0800-1700 (6/113 or 5.3%). The highest rate was found to be
      junior registrars between the hours of 1700-2200 (39/167 or 23.3%). It is
      especially interesting to note the relatively low rate (31/437 or 7.1%) obtained
      by junior registrars during the night shift (2200-0800 hours). CONCLUSIONS: The
      current overall remanipulation rate is acceptable. The low rate between 2200-0800
      hours means rescheduling of these patients is unnecessary. The rate for junior
      registrars between 1700-2200 hours needs to be improved.

PMID- 9251710
TI  - Surveillance for antimicrobial resistance in enterococci.
AB  - AIM: To describe antimicrobial resistance patterns of Enterococcus species in
      Auckland. BACKGROUND: Antimicrobial resistant enterococci have emerged as major
      nosocomial pathogens in overseas hospitals. It is recommended that hospitals
      perform periodic surveys to determine local enterococcal resistance patterns.
      METHODS: Enterococcal isolates from four patient groups were tested: group I were
      recovered from routine clinical specimens; group II were stool isolates from
      patients at risk of having vancomycin resistant enterococci, eg, intensive care
      unit patients, patients receiving vancomycin, and immunocompromised patients
      receiving antibiotics; group III were enterococci from stool specimens sent for
      Clostridium difficile toxin testing; group IV were isolates from stool specimens
      submitted to a community laboratory for enteric pathogen testing. All enterococci
      isolated were tested for the presence of beta-lactamase, susceptibility to
      amoxycillin, teicoplanin, vancomycin, and for high level gentamicin and
      streptomycin resistance. RESULTS: There were 121 group I enterococcal isolates.
      628 stool specimens were cultured. Enterococci were isolated from: 76/148 (51%)
      group II specimens; 166/279 (60%) group III specimens; and 70/201 (35%) of group
      IV specimens. Antimicrobial susceptibility testing was performed on 433 isolates;
      74% were E faecalis, 12% E faecium, 6% E gallinarum/casseliflavus group and 8%
      other enterococcal species. No isolate produced beta-lactamase. All E faecalis
      were susceptible to amoxycillin. Two E faecium and one enterococcus species were
      resistant to amoxycillin (MICs all 16 mg/L). All isolates were susceptible to
      teicoplanin. Fourteen E gallinarum/casseliflavus group isolates had intermediate
      susceptibility to vancomycin (MICs of 8 mg/L). One E faecium had intermediate
      susceptibility to vancomycin (MIC 8 mg/L). High level gentamicin and streptomycin
      resistance occurred in 64 (15%) and 50 (12%) isolates respectively. CONCLUSION:
      Vancomycin resistance is rare and is essentially restricted to species that are
      rarely clinical pathogens, i.e., E casseliflavus and E gallinarum. Our results
      have established the local susceptibility profile for enterococcal isolates. This
      allows comparison with other locations and the detection of emerging trends of
      resistance.

PMID- 9251711
TI  - A study of general practitioners' skin surgery in Canterbury.
AB  - AIMS: To evaluate skin surgery done by general practitioners in Christchurch.
      METHODS: Twenty-eight general practitioners performing regular skin surgery were
      studied. Their clinical accuracy and completeness of excision was analysed. Skin
      lesions referred for specialist treatment were also studied. RESULTS: Three
      hundred and three lesions were sent to the laboratory for analysis by
      participating practitioners. Sixty-one malignancies were present comprising 29
      basal cell carcinomas, 28 squamous cell carcinomas, three malignant melanomas and
      one cutaneous lymphoma. Nineteen of the 61 malignant lesions were incompletely
      excised. Twenty eight further lesions were referred to specialists for treatment.
      CONCLUSIONS: General practitioners in Canterbury perform more skin surgery and
      remove more malignant lesions than their British counterparts. Although the
      adequacy of their skin surgery is better than other groups studied overseas there
      is considerable room for improvement.

PMID- 9251712
TI  - Recrudescence of Plasmodium falciparum malaria contracted in Lombok, Indonesia
      after quinine/doxycycline and mefloquine: case report.
AB  - A patient is reported who contracted Plasmodium falciparum malaria in Lombok,
      Indonesia. The infection recrudesced after quinine/doxycycline and mefloquine.
      Treatment with halofantrine was successful after he developed cerebral malaria
      with recovery.

PMID- 9251713
TI  - Medicine on the margins: perspectives of abortion operating surgeons in southern
      New Zealand.
AB  - AIMS: This research surveys operating surgeon perspectives on their work with a
      view to providing information relevant to improving access to abortion services.
      METHODS: In depth interviews were held with 14 abortion operating surgeons in the
      southern region. Interviews were transcribed and analysed according to emergent
      themes. RESULTS: Operating surgeons reported their work as technically
      uninteresting but felt an obligation to provide a safe service and derived
      important satisfaction from helping patients. They valued peer support in the
      workplace and did not feel isolated from colleagues or lacking professional
      status. They noted that the introduction of medical abortions would provide
      opportunities to improve access. DISCUSSION: Mainstreaming abortions into other
      gynaecology services might improve the work environment for operating surgeons
      and training opportunities for doctors. Increased use of medical abortion
      techniques, may encourage doctors to become operating surgeons and improve access
      to services in some localities.

PMID- 9251714
TI  - Prevention of hepatitis B in healthcare workers (HCW)

PMID- 9251715
TI  - Patterns of drug use in dependent opioid users in methadone treatment.

PMID- 9251716
TI  - Measles control.

PMID- 9251717
TI  - Dr RJ Rankin guilty of professional misconduct.

PMID- 9251718
TI  - 10th Symposium on Molecular Biology of Hematopoiesis and Treatment of Leukemias
      and Lymphomas. Hamburg, Germany July 2-6, 1997. Abstracts.

PMID- 9251719
TI  - Adjuvant treatment of colorectal cancer.

PMID- 9251720
TI  - Pharmacokinetic studies in cancer chemotherapy: usefulness in clinical practice.

PMID- 9251721
TI  - Aromatase inhibitors and breast cancer.

PMID- 9251722
TI  - Peroxisome proliferator nafenopin potentiated cytotoxicity and genotoxicity of
      cyclophosphamide in the liver and bone marrow cells.
AB  - Peroxisome proliferators are ubiquitous rodent hepatocarcinogens, known to
      modulate the activities of xenobiotic-metabolising enzymes such as glutathione S
      transferases (GST) and mixed-function oxidase (cytochrome P-450). In addition
      these compounds induce pleiotropic changes in the liver of rodents even after a
      short-term treatment. It has been hypothesised that the enzymatic and cellular
      changes induced by peroxisome proliferators may alter the toxicity of other
      compounds activated by cytochrome P-450 and detoxified by GST isoenzymes. The
      effect of nafenopin-induced changes in the liver of rats on the toxicity of an
      anti-cancer drug cyclophosphamide was studied using cyto- and geno-toxicity
      parameters in the liver and bone marrow cells. The administration of
      cyclophosphamide (10 or 20 mg/kg bw) to the rats pre-treated with 80 mg/kg bw of
      nafenopin for 2 days resulted in significantly increased cytotoxic response in
      bone marrow cells. However, genotoxicity of cyclophosphamide was increased only
      in the liver of nafenopin pre-treated rats. Low level of genotoxicity in bone
      marrow could be accounted for potentiated cytotoxicity of cyclophosphamide. These
      events coincided with a significant, up to 5-fold, increase in indirect
      activation-detoxication index for cyclophosphamide, determined as a ratio of ECOD
      and GST activities, in nafenopin treated rats. This resulted from the induction
      of ECOD responsible for the formation of reactive metabolites of cyclophosphamide
      and reduced activity of GST responsible for their detoxication. In addition,
      mitotic activity of hepatocytes was increased in nafenopin treated rats that
      might also have an impact on the genotoxicity of cyclophosphamide in this organ.

PMID- 9251724
TI  - The chemistry of perfluoroisobutylene (PFIB) with nitrone and nitroso spin traps:
      an EPR/Spin trapping study.
AB  - While applying electron paramagnetic resonance (EPR)/Spin Trapping techniques,
      several reactive intermediate species were identified in the reaction of
      perfluoroisobutylene (PFIB) with nitrone and nitroso spin trap agents: the carbon
      dioxide radical anion (CO2.-), a carbonyl fluoride intermediate (COF), and vinyl
      carbanions of PFIB. The reaction of PFIB with N-t-butyl-alpha-phenylnitrone (PBN)
      forms a dipolar ion which undergoes electron transfer reactions generating stable
      nitrone spin adducts. Nitroso compounds reacted with carbanions derived from
      PFIB, which raises the possibility that electron transfer reactions of this type
      might account for the observed nitroxides. Our results suggest that PFIB
      undergoes some type of electron transfer reaction leading to several reactive
      intermediate species (RIS). The implications of these observations on pulmonary
      damage caused by inhalation of PFIB are discussed.

PMID- 9251723
TI  - The role of glutathione conjugation in the development of kidney tumours in rats
      exposed to trichloroethylene.
AB  - Trichloroethylene is metabolised to a very minor extent (< 0.01% of the dose) by
      conjugation with glutathione, a metabolic pathway which leads to the formation of
      S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a bacterial mutagen and nephrotoxin
      activated by the renal enzyme beta-lyase. The role of this metabolic pathway in
      the development of the nephrotoxicity and subsequent tumour formation seen in
      rats exposed to trichloroethylene has been evaluated. The pathway has been
      assessed quantitatively in vivo in rats, and in rats, mice and humans in vitro.
      Trichloroethylene was found to be a very weak nephrotoxin. There was no evidence
      of morphological change in the kidneys and only small increases in biochemical
      markers of kidney damage in rats dosed with 2000 mg/kg trichloroethylene by
      gavage for 42 days. N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine was detected in the
      urine of rats dosed with 500 and 2000 mg/kg trichloroethylene for up to 10 days
      at levels equivalent to 0.001-0.008% of the dose. In vitro, the rate of
      conjugation of trichloroethylene with glutathione in the liver was higher in the
      mouse, 2.5 pmol/min per mg protein, than the rat, 1.6 pmol/min per mg protein,
      and in human liver the rates were extremely low, 0.02-0.37 pmol/min per mg
      protein. Comparisons of the metabolism of DCVC by renal beta-lyase and N-acetyl
      transferase showed that metabolism by N-acetyl transferase was two orders of
      magnitude greater than that by beta-lyase and that beta-lyase activity in rat
      kidney was 11-fold greater than that in human kidney. When the nephrotoxicity of
      DCVC was compared in rats and mice, the mouse was found to be 5-10 fold more
      sensitive than the rat. The no effect level in the rat was 10 mg/kg, a dose which
      is three orders of magnitude higher than the amount of DCVC formed from
      trichloroethylene in vivo. The lack of correlation between metabolism by this
      pathway and the rat specific tumours, together with questions concerning the
      potency of DCVC at the levels formed from trichloroethylene, suggests that DCVC
      may not be involved in the renal toxicity and subsequent tumour development seen
      in rats and that further evaluation of the mechanism(s) involved in the
      nephrotoxic response is warranted.

PMID- 9251725
TI  - Lack of evidence for the involvement of formaldehyde in the hepatocarcinogenicity
      of methyl tertiary-butyl ether in CD-1 mice.
AB  - The oxygenated fuel additive methyl tertiary-butyl ether (MTBE) induced
      hepatocellular adenomas in female but not male CD-1 mice exposed to 8000 ppm;
      liver cancer was not induced in female or male mice exposed to 3000 or 400 ppm.
      Since MTBE is metabolized by cytochrome P450 to formaldehyde (HCHO), a
      potentially mutagenic intermediate capable of forming DNA-protein cross-links
      (DPX), the formation of DPX and of another HCHO derivative, RNA-formaldehyde
      adducts (RFA), from MTBE was investigated using freshly isolated hepatocytes from
      female CD-1 mice incubated with MTBE-(O-methyl-14C). DPX and RFA were detected,
      but the adduct yields were very small and were independent of the concentration
      of MTBE in the hepatocyte suspension over a wide concentration range (0.33-6.75
      mM). Similar results were obtained using hepatocytes from male B6C3F1 mice and
      male F344 rats. Induction of cytochrome P450 by pretreatment of mice with MTBE
      prior to isolation of hepatocytes did not result in a measurable increase in the
      yields of either DPX or RFA. In contrast to the absence of concentration
      dependent DPX and RFA formation from MTBE, there was a marked, concentration
      dependent increase in the yields of both DPX and RFA when [14C]formaldehyde was
      added directly to the medium. These results suggest that the metabolism of MTBE
      to HCHO approaches saturation at concentrations below 0.33 mM, and that the rate
      of HCHO production from metabolism of MTBE is slow relative to the rate of HCHO
      metabolism. The lack of concentration dependence and the absence of species or
      sex differences in the formation of DPX and RFA from MTBE indicate that
      metabolism of MTBE to HCHO is not a critical component of its carcinogenic
      mechanism in mice.

PMID- 9251726
TI  - Interaction of some organic platinum (II) complexes with L5178Y-R and L5178Y-S
      cells.
AB  - The cytotoxicity and mutagenicity of three organic platinum(II) complexes 1-3
      have been studied in two strains of murine lymphoma L5178Y cells. (1) [Pt(Amp)Cl]
      (S,N,N) (Amp, ampicillin); (2) [Pt(Met(O))Cl2] (S,N), (met(O), L-methionine
      sulfoxide); (3) [Pt(Met(O))(R-IDA)] (S,N) [N,N), (R-IDA, 2,4-N
      (dimethylacetanilide)-iminodiacetic acid). It has been confirmed that the
      cytotoxic and mutagenic action of Pt-complexes depends on the structure of stable
      ligand and the number and structure of the leaving groups. The highest
      cytotoxicity and mutagenicity was found in cells treated with the
      dichloromethioninesulfoxideplatinum(II) complex.

PMID- 9251727
TI  - Second malignant neoplasms in patients treated on SIOP Wilms tumour studies and
      trials 1, 2, 5, and 6.
AB  - The incidence of second malignant neoplasms (SMNs) was investigated among 1,988
      patients with complete data, enrolled in the SIOP Wilms tumor trials and studies
      1, 2, 5, and 6, treated between September 1971 and October 1987. By the end of
      1992, eight SMNs were documented, whereas only 1.3 were expected (standardized
      incidence ratio [SIR] = 4.15; 95% CI = 1.79, 8.17). The risk increases in the
      first 10 years from diagnosis, while no apparent excess of risk is observed in
      the subsequent periods. This finding however is difficult to interpretdue to the
      low statistical power. The cumulative incidence of a second cancer observed at 15
      years after Wilms tumor diagnosis was 0.65%. Six SMNs were registered in the
      cohort of patients treated in the SIOP studies 1, 2 and 5 (999 cases) compared to
      the two cases observed in the SIOP6 cohort (989 cases). If the suggested reduced
      incidence of second cancers between SIOP1-5 and SIOP6 patient cohorts is
      confirmed by longer follow-up, it might reflect changes in the treatment
      protocols.

PMID- 9251728
TI  - Veno-occlusive disease of the liver in children treated for Wilms tumor.
AB  - INTRODUCTION: Hepatotoxicity consistent with the clinical diagnosis of veno
      occlusive disease (VOD) of the liver has been suspected after conventional anti
      cancer chemotherapy in children. METHODS: To establish the incidence of
      hepatotoxicity and its relationship with VOD, we analyzed toxicity data obtained
      on 511 children affected by Wilms tumor and treated according to the SIOP-9
      protocol. They all received pre- and postnephrectomy chemotherapy using
      dactinomycin (AD) and vincristine (VCR) +/- other drugs +/- radiotherapy
      according to surgical stage and histology. RESULTS: Sixty-four patients suffered
      at least one episode of hepatotoxicity and 41 satisfied the criteria for a
      clinical diagnosis of VOD. In this latter group, toxicity occurred during
      preoperative treatment in 15 patients and was confirmed histopathologically in 9
      of the 16 liver biopsies obtained. There was a higher percentage of children aged
      less than 1 year at diagnosis in the VOD group than in the other patients (24%
      vs. 11.4%). The degree of liver damage in the younger patients seems important,
      as suggested by a higher increase in transaminases. VOD developed in 12% of the
      68 irradiated children vs. 7% in the non-irradiated group. Statistical analysis
      showed an increased risk of VOD in younger patients (p < 0.001) and in those
      receiving radiotherapy (p < 0.001). All patients recovered after 6-180 days using
      supportive therapy only. CONCLUSIONS: (1) 8% of children treated according to the
      SIOP-9 protocol, developed hepatotoxicity consistent with VOD. Excluding patients
      who received radiotherapy, the incidence was 6%. These figures are much higher
      than in earlier reports, though different diagnostic criteria were used. (2)
      Chemotherapy with AD and VCR seems to be a major cause of VOD. (3) Risk factors
      are young age and concomitant radiotherapy. (4) VOD does not prejudice positive
      outcome for these patients.

PMID- 9251729
TI  - Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia: 6
      mercaptopurine dosage strategies.
AB  - Daily 6-mercaptopurine (6MP) forms the backbone of continuing chemotherapy for
      childhood lymphoblastic leukaemia (ALL). A major metabolic route is catalysed by
      thiopurine methyltransferase (TPMT). TPMT deficiency occurs in 1 in 300
      individuals and results in high concentrations of thioguanine nucleotides (TGNs),
      cytotoxic 6MP metabolites. A leukaemic child taking 6MP repeatedly developed
      profound pancytopenias. TPMT deficiency was confirmed. TGN formation was then
      studied on attenuated 6MP dosages. Four weekly oral doses of 75 mg/m2 6MP
      produced TGNs of 2348 pmol/8 x 10(8) red cells, nearly double the maximum TGNs
      recorded in ALL children with TPMT activity taking long term daily 75 mg/m2 6MP.
      Grossly elevated TGN concentrations were also produced at 10% standard 6MP dosage
      (7.5 mg/m2 daily), accompanied by unacceptable 6MP toxicity (neutropenia,
      diarrhoea, vomiting). The child was eventually stabilised on 10% alternate day
      therapy and after 15 weeks TGNs were 1670 pmol, just above the upper end of the
      TGN range for ALL children with TPMT activity.

PMID- 9251730
TI  - Successful treatment of relapsed infant acute lymphoblastic leukemia with
      intensive antimetabolite-based chemotherapy.
AB  - PURPOSE: The treatment of infant acute lymphoblastic leukemia (ALL) continues to
      be a significant challenge for pediatric oncologists due to the high incidence of
      early relapses. Salvage regimens used to date have met limited success. We
      describe two cases of relapsed infant ALL who have achieved long-term survival
      with an intensive antimetabolite-based salvage regimen. PATIENTS AND METHODS: Two
      consecutive infants with relapsed ALL presented at our institution and were
      treated with an antimetabolite-based regimen. Both cases exhibited clinical and
      biological phenotypes previously associated with infantile ALL. RESULTS: Both
      patients have achieved prolonged and sustained remissions 48 and 30 months EFS
      respectively following therapy with intensive antimetabolite-based salvage
      regimen. CONCLUSIONS: An intensive multiagent antimetabolite based salvage
      regimen resulted in prolonged EFS in two cases of relapsed infant ALL. Dose
      intensification was achieved by administering repeated cycles of the same
      treatment schema using high dose chemotherapy throughout therapy. These infants
      were spared prophylactic cranial irradiation without a negative impact on
      outcome. The use of L-asparaginase, timed after high-dose Cytarabine (ARA-C)
      throughout therapy, might have contributed to their cure.

PMID- 9251731
TI  - Osteonecrosis in children treated for acute lymphoblastic leukemia: a magnetic
      resonance imaging study after treatment.
AB  - The purpose of the study was to find out the prevalence of osteonecrosis in
      children with acute lymphoblastic leukemia (ALL) in complete bone marrow
      remission at the end of the treatment. Twenty-eight children with ALL underwent
      MRI of the upper and/or lower extremities. Bone marrow signal intensity was
      analyzed on T1-weighted images, where circumscribed lesions with a rim of low
      signal intensity were considered typical of osteonecrosis. Osteonecrosis was
      found in 9 of the 28 children (32%, 95% CI 16% to 52%). Five of them were
      asymptomatic. They had been treated with high risk and intermediate risk
      protocols, both of which include a delayed intensification phase with
      dexamethasone. None of the patients with standard risk ALL were found to have
      developed osteonecrosis. Osteonecroses occurred unexpectedly in symptomless
      patients and in patients with mild transient symptoms treated with high risk and
      intermediate risk protocols. Our study suggests that the intensification phase of
      the treatment protocols with intensive dexamethasone medication might be
      responsible for the development of osteonecrosis.

PMID- 9251732
TI  - Abdominal ultrasound findings during and after treatment of childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: The treatment of acute leukemia in childhood has been increasingly
      successful. Concurrently, severe leukemia-related gastrointestinal complications
      have become more common. METHODS: We evaluated the findings of the abdominal
      ultrasound (US) examinations of 52 children with acute lymphoblastic leukemia
      (ALL) who had severe clinical symptoms indicating infection or abdominal
      complication during chemotherapy treatment or after the cessation of such
      treatment and assessed the impact of these findings on patients' subsequent
      treatment and survival. RESULTS: Our study presents ten cases of typhlitis with a
      prevalence of 9%, all of which were rapidly diagnosed by US and had a favourable
      outcome. We also found focal intra-abdominal parenchymal lesions in six children,
      five of them due to fungal infection and one due to leukemic infiltration.
      Several other intra-abdominal pathologies significant for the patients' treatment
      are also reported. DISCUSSION: We believe that abdominal US is a useful, rapid,
      safe, and accurate imaging method for children with ALL suspected to suffer from
      leukemia- or chemotherapy-related gastrointestinal complications. More invasive
      imaging methods are seldom needed. CONCLUSIONS: According to our results,
      abdominal US gives the necessary information in most of the cases and provides
      prompt diagnosis, which may prevent possible fatal complications.

PMID- 9251733
TI  - Excess of congenital abnormalities in French-Canadian children with
      neuroblastoma: a case series study from Montreal.
AB  - Neuroblastoma is one of the most common cancers of childhood. Some studies have
      shown an excess of congenital abnormalities in children who have been diagnosed
      with neuroblastoma. In this study we examined the medical records of all children
      with neuroblastoma seen at St. Justine Children's Hospital between the years 1977
      and 1993. A total of 141 children (131 of French-Canadian ancestry) were included
      in this study. Twelve children (8.5%) had 21 defined congenital abnormalities
      (1,490 per 10,000 children). This compared with a rate of 444.3 children with
      abnormalities per 10,000 live births (4.44%) for all congenital abnormalities in
      the British Columbia Health Surveillance Registry, 1979-1988 (relative risk =
      1.91, P = 0.03). Six of the 12 children had cardiovascular malformations. These
      and previous results suggest that there may be a common developmental origin to
      neuroblastoma and to some congenital malformations. Genes that control
      development may be worthy of further study in these children.

PMID- 9251734
TI  - Increased LH and FSH secretion after cranial irradiation in boys.
AB  - The effect of high-dose cranial- and craniospinal irradiation and chemotherapy on
      the gonadotropin-sex steroid axis was studied during different stages of puberty
      by measuring pulsatile secretion of luteinizing hormone (LH), follicle
      stimulating hormone (FSH) and testosterone. The patients were thirteen boys who
      had been treated for malignant brain tumor residing well away from the
      hypothalamo-pituitary region. The median time to follow-up was 9 (1-16) years.
      The onset of puberty was early in the patients, median 10.5 years, compared to
      the average age for Swedish boys, which is at median 12.4 years. There was,
      before puberty, no significant difference in LH and FSH secretion between
      patients and a control group of normal boys. In early, mid- and late stages of
      puberty, however, LH and FSH secretion was increased in the patients overall,
      whereas testosterone secretion was maintained within the normal range in spite of
      signs of gonadotoxocity with small testicular volumes. These results indicate
      that the vulnerable parts of the gonadotropin releasing hormone (GnRH)
      gonadotropin (LH, FSH)-gonadal axis are the regulatory system that determines the
      timing of pubertal induction and the gonads. The GnRH-LH, FSH-releasing neurons
      appear relatively resistant to cranial irradiation as they are able to respond
      with supranormal LH and FSH levels for long periods of time after treatment.

PMID- 9251735
TI  - 2-Chlorodeoxyadenosine (2-CDA) for the treatment of refractory or recurrent
      Langerhans cell histiocytosis (LCH) in pediatric patients.
AB  - BACKGROUND: Pediatric patients with Langerhans cell histiocytosis (LCH) may
      become refractory to conventional therapy or present with repeated recurrences
      over several years. Current therapeutic options such as prednisone, vinblastine,
      etoposide, and cyclosporine are associated with significant acute toxicities and
      late effects. Recent reports suggested that 2-chlorodeoxyadenosine (2-CDA) may be
      an effective agent in adults with LCH. The purpose of this study was to determine
      the safety and efficacy of 2-CDA in children with LCH. METHODS: This report
      presents the data collected from the first three patients that have completed
      this trial. Patients were enrolled in a prospective study after informed consent
      was obtained. Patients had a confirmed diagnosis of LCH that had recurred several
      times or not responded to standard therapy. Patients were given a starting dose
      of 5 mg/M2 of daily continuous infusion for three days duration. Two patients had
      their dose increased to 6.5 mg/M2/ day. A total of 4-6 courses were given, and
      courses were repeated every 3-4 weeks. Thirteen of fifteen courses were given as
      outpatients at home. RESULTS: Each patient completed therapy with
      myelosuppression the primary toxicity. Pt. 1 initially received a higher dose of
      2-CDA and developed sepsis. The dose was reduced to current study levels and no
      other incidence of infection, fever, and neutropenia, or blood product
      transfusion was required. All three patients are free of active disease 10-18
      months after completing 2-CDA. CONCLUSION: Three patients with LCH refractory to
      standard therapy had CR to 2-CDA, given at 5-6.5 mg/M2/day for 3 days, without
      significant toxicity.

PMID- 9251736
TI  - Treatment of spinal cord tumors in children.
AB  - BACKGROUND: A retrospective review was carried out of nine children under 17
      years of age with a diagnosis of intramedullary tumor seen during the period 1989
      1995. Six had astrocytomas; one each had an ependymoma, a PNET, and a choroid
      plexus papilloma. Five patients had back pain, 3 others had mild pareses and the
      ninth had incapacitating defects. Seven of the 9 were treated by subtotal
      extirpation of the lesion, and biopsy alone was performed in the other two. All
      tumors were low grade (grade I or II) and therefore radiation therapy (RT) was
      performed as the only postoperative treatment in 8 of the 9 children. RESULTS: In
      February 1996, seven (77.8%) children were alive and two (22.2%) died of
      recurrent tumor (7 months and 5 years after diagnosis, respectively). Median
      follow-up was 3 years 4 months (range: 1 year 6 months to 7 years 3 months).
      CONCLUSION: Surgical removal of intraspinal tumors provides the best hope of
      control, but spinal column deformity after laminectomy and irradiation is a
      serious long-term problem in children. Orthopedic supervision for the prevention
      of these deformities; e.g., by external immobilization, is mandatory.

PMID- 9251737
TI  - Dural sinus thrombosis in children with cancer.
AB  - Dural sinus thrombosis (DST) has been reported in association with cancer in both
      adults and children. We describe the seven patients seen with this complication
      in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral
      CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six
      patients were boys. Six children were being treated for non-Hodgkin lymphoma and
      one for neuroblastoma. Presenting symptoms were seizures and transient neurologic
      deficit, often preceded by headaches. The probable cause of DST was found in two
      cases. Tumour localisation in the central nervous system (CNS) probably caused
      DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination
      with a poor general condition seemed to be the cause of DST in the patient with
      neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three
      lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In
      these children, DST occurred early in the course of therapy. The median interval
      between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No
      child had received L-asparaginase. Prognosis was favourable, with symptoms
      completely disappearing without therapy within 1 to 5 days. The incidence of DST
      in patients with advanced stage non-Hodgkin lymphoma during induction and
      consolidation was calculated to be below 3%. We conclude that DST is rarely
      diagnosed in children with cancer. Occurrence during the initial phase of therapy
      for non-Hodgkin lymphoma is associated with a benign prognosis.

PMID- 9251738
TI  - Endodermal sinus tumors in the head and neck region.
AB  - Extragonadal germ cell tumors of the head and neck region account for only 5% of
      all benign and malignant germ cell tumors. Endodermal sinus tumors (EST) of the
      head and neck region are rare. We report three patients with EST of head and neck
      region over a period of 10 years; the primary sites of tumor were orbit,
      maxillofacial region and retroauricular region. Histopathological examination
      revealed malignant teratoma with predominant endodermal sinus pattern in two, and
      pure EST in one patient. Serum alpha fetoprotein (AFP) was elevated in all three
      patients. Two patients had initial surgery but did not receive adjuvant
      chemotherapy, as the parents refused it. Partial remission was achieved in the
      other patient who received chemotherapy (cisplatin, bleomycin and vinblastin) and
      the patient died of infection after four courses of chemotherapy.

PMID- 9251739
TI  - Metastatic primitive neuroectodermal tumour of the ovary: successful treatment
      with mega-dose chemotherapy followed by peripheral blood progenitor cell rescue.
AB  - Primitive neuroectodermal tumours (PNET) of the ovary are rare, aggressive
      tumours which are associated with high morbidity and mortality. Previously
      reported cases have shown limited response to therapy in patients presenting with
      metastatic disease and survival rates have been discouragingly low. We report the
      case of a 13-year-old girl who presented with a primary ovarian PNET and
      extensive metastatic disease. Pathologic studies confirmed the neural origin of
      the tumour and its morphologic appearance of neuroblastoma. Incomplete surgical
      resection was followed by treatment with aggressive multi-agent chemotherapy
      including cis-platinum, etoposide, cyclophosphamide, anddoxorubicin as per a
      neuroblastoma treatment protocol. Complete clinical remission ensued and she
      received consolidative therapy with myeloablative doses of thiotepa, melphalan,
      and carboplatin followed by autologous peripheral blood progenitor cell rescue.
      All therapy was well tolerated and the patient remains in complete remission with
      no evidence of disease 18 months from presentation. Mega-dose chemotherapy
      followed by progenitor cell rescue may provide optimal therapy for patients
      presenting with metastatic ovarian PNET.

PMID- 9251740
TI  - Clinical usefulness of CT in the treatment of stage I endometrial carcinoma.
AB  - This retrospective study was aimed at assessing Computed Tomography (CT)
      capabilities in identifying low- and high-risk groups of clinical stage I
      endometrial carcinoma patients. CT of the pelvis was performed on 125 endometrial
      carcinoma patients who were divided into two groups based on T (stage and depth
      of myometrial invasion) and N (lymph node status) parameters. All patients had
      histologic evidence of well/moderately-differentiated adenocarcinoma (G1-G2). The
      low-risk group consisted of stage I patients with superficial myometrial
      involvement and no lymphadenopathy, while the high-risk group consisted of the
      patients with deep myometrial invasion and/or stage II and/or positive lymph
      nodes. All patients were operated on-i.e., total abdominal hysterectomy with
      vaginal cuff, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The
      patients were followed-up for 36 months at least. On the basis of CT findings, 85
      patients were included in the low-risk group, but 11 misstaged cases were found
      at surgery in which lymphadenectomy never changed the factor risk. Only four
      relapses (4.7%) were observed in this group. Forty patients were included in the
      high-risk group: CT misstaged 20 cases and 12 relapses (30%) were observed. This
      study demonstrates the clinical value of CT in the assessment of radiologic risk
      factors in stage I endometrial carcinoma; CT findings can be used as guidelines
      for different treatments.

PMID- 9251741
TI  - Wiener spectrum of radiographic systems: comparison of different evaluation
      methods.
AB  - The noise power spectrum, or Wiener spectrum, of the radiographic mottle is a
      fundamental quantity in film-screen image quality evaluation. In this paper,
      using a high-quality computerized microdensitometer, two different acquisition
      and calculation methods for noise evaluation are compared. The first one is the
      classic (unidimensional) method used in film noise evaluation: a long and narrow
      slit (10 x 400 microns2) is used to delimit the microdensitometer light beam and
      the transmission data are collected by scanning the sample in a rectilinear
      pattern. A section of the two-dimensional Wiener spectrum is thus obtained. The
      second (two-dimensional) method is similar to that used in digital image noise
      evaluation: a square slit is used on the microdensitometer window and data are
      collected by scanning the sample on a square pattern. To evaluate the effect of
      different sampling frequencies, our data were acquired both selecting a 50 x 50
      microns2 square slit and a 20 x 20 microns2 square slit. The two-dimensional
      Wiener spectrum thus obtained is then reduced to a unidimensional function. The
      measurements were made on two different films (Kodak Ortho G e Kodak T-MAT G)
      exposed with the same screen (Kodak Lanex Regular). These films have the same
      sensitivity but a different emulsion structure. One film (Ortho G) is made of
      irregular halide silver grains and the other (T-MAT G) of tabular grains. A
      satisfactory agreement between the two procedures was found which makes the
      comparison of data from the laboratories using microdensitometers and those using
      TV-grabbing system for film-screen evaluation meaningful.

PMID- 9251742
TI  - An uncommon heart tumor: the fibrosarcoma.

PMID- 9251743
TI  - In memoriam Professor Mario Penna, MD.
AB  - In memoriam Mario Penna. Born in Ovalle, Chile, February 12, 1924. MD, University
      of Chile. Professor of Pharmacology, Faculty of Medicine, University of Chile.
      Chairman, Department of Pharmacology; Director, Department of Experimental
      Medicine, Eastern Division, University of Chile. President, Latin American
      Association of Pharmacology. Member of the Advisory Committee of this journal,
      under its previous name of "Archivos de Biologia y Medicina Experimentales",
      between 1966 and 1987. Deceased in Santiago, Chile, June 25, 1994.

PMID- 9251744
TI  - Expression of active human erythropoietin in the mammary gland of lactating
      transgenic mice and rabbits.
AB  - Transgenic mice and rabbits were generated using a chimeric gene comprising the
      human erythropoietin (hEPO) cDNA under the 5' and 3' regulatory sequences of the
      rabbit whey acidic protein gene. Transgenic mice expressed hEPO at levels of 0.01
      mg/l in the milk of lactating females showing that the genetic construct was
      functional. Reverse transcriptase polymerase chain reaction with RNA from various
      tissues showed that this transgene was expressed mainly in the ovary and mammary
      gland. In rabbits, we demonstrated the germ line transmission of the transgene.
      The hEPO was obtained in the milk of lactating females at levels of up to 0.0003
      mg/l. Although the expression levels were low, biologically active hEPO was
      obtained in the milk of transgenic rabbits without any apparent detrimental
      effect for the animals. In vitro, the specific activity of the rabbit-derived
      hEPO was higher than that reported for the natural hEPO, thus suggesting
      differences in the glycosylation pattern in at least part of the molecules
      secreted by the mammary gland of transgenic rabbits.

PMID- 9251745
TI  - Neuroendocrine mechanisms of lactational infertility in women.
AB  - The current knowledge on the mechanisms of lactational infertility, discussed
      during a symposium of investigators in this subject, is reviewed. Three periods
      of lactation are examined: the first weeks postpartum, the period of extended
      lactational amenorrhea and the recovery of ovarian function. In the first
      postpartum weeks the inhibition of ovarian function is accounted by diminished
      pituitary response to GnRH, since exogenous GnRH fails to elicit a LH increase.
      Suckling can extend the period of ovarian inhibition for weeks, months or years,
      although it does not fully suppress pulsatile secretion of LH beyond the first
      weeks. Extended lactational amenorrhea is associated with low LH plasma levels, a
      great PRL increase in response to suckling, low basal E2 levels and a suppression
      of estrogen positive feedback. Decreased immunoreactive LH levels may result from
      partial suppression of the LH pulse generator and a smaller mass of GnRH released
      in each burst. The role of neurotransmitters, PRL and ovarian factors is
      discussed. After the recovery of ovulatory cycles suckling still has a residual
      infertility effect, associated to inadequate luteal function. The sources of
      variation among women and populations were recognized. Areas in which research is
      needed to improve the understanding of the mechanisms that sustain lactational
      amenorrhea are suggested.

PMID- 9251746
TI  - Relative participation of adenosine and endothelium derived mediators in coronary
      reactive hyperemia in the dog.
AB  - The metabolites that mediate coronary reactive hyperemia have not been definitely
      identified. Although adenosine and endothelium derived substances seem to be
      involved, their relative contributions have not been defined yet. In the canine
      coronary circulation, we studied the relative participation of adenosine, nitric
      oxide and prostacyclin in reactive hyperemia, by measuring the changes produced
      by interfering with the synthesis or action of these metabolites. The dose
      response curve for flow changes vs intracoronary administration of adenosine was
      displaced to the right after the inhibition of nitric oxide synthesis with N
      omega-nitro-L-arginine, revealing that nitric oxide release partly mediates the
      vasodilator action of adenosine. The inhibition of PGI-2 synthesis with
      indomethacin did not modify reactive hyperemia. Interference with adenosine
      action, by administration of adenosine deaminase plus theophylline, decreased
      reactive hyperemia by 31.0 +/- 4.0% (p < 0.001). Inhibition of nitric oxide
      synthesis decreased reactive hyperemia by a larger (p < 0.005) magnitude, 41.0 +/
      3.9% (p < 0.001), revealing the existence of other stimuli for nitric oxide
      release in reactive hyperemia besides adenosine. Simultaneous inhibition of
      nitric oxide and PGI-2 syntheses and of adenosine action reduced reactive
      hyperemia, but the effect was not additive, reaching 49.5 +/- 4.5% of control.
      Since nitric oxide and adenosine are the most important mediators in reactive
      hyperemia so far described, our results suggest that other metabolites, acting
      directly or through mediators other than adenosine or nitric oxide, are
      responsible for about 50% of coronary reactive hyperemia.

PMID- 9251747
TI  - Arginase activity in Bufo arenarum embryos.
AB  - The evolution of arginase activity during development of Bufo arenarum embryos
      was studied. The enzyme activity was detected after the neural groove stage,
      being low at the following early stages and increasing progressively until the
      end of the embryonic development. Arginase activity was first found in the
      neurula stage, when an outline of basic structures for renal and hepatic function
      is present. The activity increased two- or three-fold at the beginning of the
      larval stages.

PMID- 9251748
TI  - Evolutionary origins of the reptilian brain: the question of putative homologues
      of dorsal ventricular ridge. An overview and proposal.
AB  - The reptilian brain is characterized by a structure that bulges into the lateral
      ventricle, called dorsal ventricular ridge (DVR). The DVR was originally
      considered to be a part of the basal ganglia, although more recent studies
      indicate that it may correspond to the dorsal part of the hemisphere. The
      anterior portion of the DVR has several connectional and functional similarities
      with parts of the mammalian neocortex, for which reason it has been claimed that
      the two structures can be considered as homologues. In this article I review the
      evidence supporting and refuting homology of the DVR with different telencephalic
      structures of mammals, concluding that it is still early to unequivocally ascribe
      structural correspondences between the different components in the two vertebrate
      classes. However, a way out of the problem is suggested by comparing the
      embryonic position of DVR with that of lateral cortex in the reptilian
      hemisphere. The lateral cortex is considered to be quite comparable in reptiles
      and mammals, and hence may be a good marker for the original position of the DVR.
      If the DVR originates dorsal to lateral cortex, it may be considered comparable
      to parts of the mammalian neocortex, while if it develops in its same position or
      ventral to it, it may not correspond to the neocortex. Early embryological work
      indicated that the DVR develops in the same position as the lateral cortex, but
      arises as a late migration wave, after cells destined to lateral cortex are
      generated. In other words, instead of being interposed between dorsal and lateral
      cortices, the DVR may originate in a position overlapping with lateral cortex. If
      this alternative turns out to be the case, it may imply that the DVR arose de
      novo, through an extension of the ancestral period of neuroblast proliferation.
      As a consequence, there may be no structures comparable to it in other vertebrate
      classes. Finally, it is also proposed that, regardless of whether the DVR and the
      extrastriate neocortex can or cannot be considered phylogenetic homologues, some
      of the integrative functions performed by them might have a common evolutionary
      origin, that became localized in the reptilian DVR and in the mammalian
      extrastriate neocortex.

PMID- 9251749
TI  - The sound of the DNA language.
AB  - A new method is described for the study of DNA language employing the
      communicative strength of music. An algorithm was created to "translate" codons
      into musical notes. The analysis of the musical transcriptions of DNA sequences
      suggests the presence of some structural features of DNA language hidden in human
      and mouse interferon alpha 1 genes.

PMID- 9251750
TI  - Invasive and enterotoxic properties in Campylobacter jejuni and Campylobacter
      coli strains isolated from humans and animals.
AB  - Invasive properties of 15 strains of thermotolerant Campylobacter (12 C. jejuni
      and 3 C. coli) were studied using HeLa cells cultures. In four of them (3 C.
      jejuni and 1 C. coli), randomly selected, intestinal perfusion experiments were
      conducted in order to asses enterotoxigenicity. All strains were able to invade
      HeLa cells. The number of invaded HeLa cells ranged from 3 to 46%. In addition to
      their invasive properties, the 4 strains used in perfusion experiments were able
      to induce either a net secretory flux or an impaired sodium transport.

PMID- 9251751
TI  - Anomalous patterns of callosal connections develop in visual cortex of
      monocularly enucleated hamsters.
AB  - In this study we analyzed the effect of neonatal monocular enucleation on the
      pattern of callosal connections in striate cortex of the golden hamster. Callosal
      connections were revealed in the hemisphere ipsilateral to the remaining eye
      following multiple injections of either the enzyme horseradish peroxidase or the
      fluorescent tracer Fluoro-Gold into the contralateral hemisphere. The most
      salient anomaly induced by the removal of one eye at birth is the appearance of a
      dense band of callosal connections that runs anteroposteriorly in medial portions
      of striate cortex. No obvious changes in the laminar distribution of callosal
      connections were observed. Comparison of our present results with those obtained
      by Olavarria et al (1987) in monocularly enucleated rats reveals that neonatal
      enucleation induces remarkably similar anomalies in the callosal patterns of rats
      and hamsters. This similarity suggests that the role the eyes play in the
      development of the visual callosal pathway is similar among rodent species.
      Moreover, the finding of an anomalous callosal band in striate cortex one-eyed
      hamsters supports the notion that disruption of visual input does not arrest
      callosal development, but rather leads to the development of entirely new
      features in the callosal pattern.

PMID- 9251753
TI  - Opposing effects of quinacrine and chloroquine on the development of TA3
      transplanted tumors in mice.
AB  - Both quinacrine and chloroquine had been used as antimalarial agents.
      Furthermore, antineoplastic and antiviral effects have been described for
      quinacrine, while chloroquine has been described to induce viral replication and
      promote tumor growth. To search for differences in the growing rate of
      transplanted tumors, chloroquine or quinacrine were administered orally to AJ
      mice from 30 days previous to the inoculation of TA3 transplantable tumor cells,
      treatment being continued up to the end of the experiment. A control group,
      transplanted with tumor cells received tap drinking water. Marked differences
      between the three groups were found. Quinacrine had antitumoral effect, while
      chloroquine promoted a faster tumoral growth than controls. (p < 0.01). Results
      suggest caution in the use of chloroquine, because it might have a similar
      promoting effect on human neoplasia.

PMID- 9251752
TI  - Effect of monocular blockade of retinal activity on the development of visual
      callosal connections in the rat.
AB  - It has been previously reported that neonatal monocular enucleation in rats and
      hamsters induces the development of an anomalous band of callosal connections in
      the middle of area 17 (primary visual cortex) in the hemisphere ipsilateral to
      the remaining eye. In order to determine whether this effect is due to
      elimination of retinal activity in one eye, we used the anatomical tracer
      horseradish peroxidase (HRP) to study the pattern of visual callosal connections
      in rats in which retinal activity had been blocked by intraocular injections of
      tetrodotoxin during the first two weeks of life. We found that the callosal
      pattern in the hemisphere ipsilateral to the eye not treated with tetrodotoxin
      was not distinguishable from the pattern present in normal rats. In particular,
      we did not observe the anomalous extra band of callosal connections that occurs
      in area 17 in the hemisphere ipsilateral to the remaining eye in monocularly
      enucleated rats. These results indicate that blockade of retinal activity in one
      eye is not sufficient to cause the marked changes in the pattern of visual
      callosal connections that are induced by neonatal monocular enucleation.

PMID- 9251754
TI  - In memoriam professor Hugo Adrian.
AB  - In memoriam Professor Hugo Adrian, born 1926, deceased 1994, in Santiago, Chile.
      After completion of his studies in veterinary medicine, he followed a successful
      career in neurophysiological research. He was Research Associate (1961-1962) and
      Visiting Professor (1973-1976) at the Neurophysiology Department University of
      Wisconsin, USA. He was the first Director (1958-1960) of the Institute of
      Physiology at the Austral University, Valdivia, and was Professor (1963-1973;
      1977-1994) and Chairman of the Department of Physiology and Biophysics,
      University of Chile, Santiago, Chile, where he led a group of researchers in
      auditory physiology, introduced the use of computer techniques to physiological
      studies, and developed several projects of applied neurophysiology.

PMID- 9251755
TI  - Plant proteinase inhibitors: a defensive response against insects. (Review).
AB  - Plants protect themselves against pests using their wide chemical defense
      arsenal. Among several defense proteins, proteinase inhibitors appear to be an
      important group. Proteinase inhibitors are widely present in plants and they are
      often found in storage organs. They are known to be inducible in plants by
      injuries, such as insect damage. Because these proteins inhibit digestive enzymes
      of insect larvae and microbial proteases, they may be considered as mechanisms to
      improve the plant defense against pests. In recent years, growing research on
      plant proteinase inhibitors has confirmed their important role in plant defense,
      although several aspects are still controversial. Although many plants have
      related proteinase inhibitors, which have been shown to affect metabolism and/or
      development of different insects, these plants do not seem to share a common
      inhibitor induction mechanism. This is an emerging field and much work is yet to
      be done.

PMID- 9251756
TI  - The effects of imidazole on pulmonary damage induced by bleomycin.
AB  - Bleomycin may produce diffuse pulmonary damage. Our objective was to evaluate the
      effect of imidazole, a thromboxane-synthetase inhibitor, on pulmonary damage
      induced by endotracheal instillation of bleomycin in rats. Bleomycin 1 U/100 g
      body weight produced diffuse pulmonary damage and increased number of
      inflammatory cells after 3 days, hemorrhage and focal fibrosis after 7 days, and
      diffuse fibrosis and pneumocyte hyperplasia after 14 to 30 days. Imidazole 5
      mg/100 g body weight, given intraperitoneally 30 min before bleomycin, decreased
      the 3rd day lesions without altering the histopathology in subsequent periods.
      Imidazole reduced (p < 0.05) the increases in cell number (3rd and 14th days) as
      well as in proteins in bronchoalveolar lavage (3rd day), without modifying the
      increase in phospholipids observed in rats treated with bleomycin. We conclude
      that imidazole decreases initial bleomycin-induced pulmonary damage, but it does
      not interfere with fibrosis and late development of epithelial hyperplasia.

PMID- 9251757
TI  - G2 repair and evaluation of the cytogenetic damage induced by low doses of X
      irradiation during G0 in human lymphocytes.
AB  - In the present study two cytogenetic parameters were used to evaluate the DNA
      damage induced by low doses (1 up to 40 rad) of X-ray irradiation in G0 human
      lymphocytes. These parameters were the frequency of chromosomal lesions in G2 and
      the length of this cell cycle phase. The frequency of chromosomal lesions in G2
      was determined by scoring the number of chromosomal aberrations in G0 irradiated
      lymphocytes post treated with two inhibitors of G2 repair mechanisms: caffeine
      and 3-aminobenzamide. A dose-dependent increase in chromosomal aberrations yield
      was detected in G0 lymphocytes X-ray irradiated with or without post treatment
      with these two DNA repair inhibitors during G2. Nevertheless, the dose response
      in this latter condition was higher than the one detected in control cells,
      indicating that the increase of irradiation dose in G0 lymphocytes produces an
      increment in the number of DNA lesions arriving to be repaired in G2. The
      analysis of the dose-response relationships for G2 length showed an statistically
      significant X-ray dose-dependent increase (G2 delay) from 2.5 up to 40 rad and a
      positive correlation between G2 delay and the frequency of chromosomal lesions in
      G2. These results suggest that the DNA lesions induced by low doses of X
      irradiation in G0 lymphocytes may be higher than that detected by the standard
      method (control conditions) and may be responsible for an increase in G2 length.
      We propose, therefore, that an analysis of these two cytogenetic parameters can
      improve the evaluation of the DNA damage induced by low doses of X-rays
      irradiation in G0 cells.

PMID- 9251758
TI  - Humoral immune response anti K99 pilus from enterotoxigenic Escherichia coli in
      experimentally inoculated calves.
AB  - The bovine model is extremely interesting to study several basic aspects of
      mucosal local immunity. Many reports have shown that, in young calves, the
      infectivity of enterotoxigenic Escherichia coli may be inhibited by passively
      administered antibodies anti K99 pilus. We have measured, by immunoradiometric
      assays, the IgG response anti K99 pilus in the serum of calves, deprived of
      colostrum and orally inoculated with enteropathogenic K99+ E. coli. Although
      variable levels of IgG anti K99 pilus were detected, their protective value could
      not be ascertained in vivo due to the acute development of the infection. In an
      effort to correlate the presence of serum antibodies anti K99 pilus with their
      protective capacity, an ex-vivo assay to monitor the interaction of radiolabeled
      K99 pilus with the bovine mucosa was standardized. Paradoxically, although K99
      pilus, purified by standard procedures, was recognized by polyclonal rabbit and
      calf antisera, its interaction with the bovine intestinal mucosa, quantitated in
      the ex-vivo system, was not inhibited by these reagents, indicating that the
      antibodies did not effectively block those K99 pilus domains involved in the
      interaction with mucosal receptors.

PMID- 9251759
TI  - Expression of interferons-alpha and -beta, tumor necrosis factor-alpha and
      transcription factors, IRF-1 and IRF-2, in leukocytes induced during interferon
      production.
AB  - Analysis of gene expression in peripheral blood lymphocytes is of special
      interest because it could reflect physiological conditions. We have examined the
      expression and compared the relative amounts of specific mRNAs for interferons
      (IFN-alpha and IFN-beta), tumor necrosis factor-alpha (TNF-alpha) and interferon
      regulatory factors (IRF-1 and IRF-2) from interferon primed and Sendai virus
      induced peripheral blood leukocytes. Results obtained showed that IRF-1 was
      highly inducible by IFN treatment, IFN-alpha, TNF-alpha and IRF-2 were weakly
      induced by IFN treatment, and IFN-beta was not inducible by priming the cells
      with recombinant human IFN-alpha 2b. The IFN-alpha, IFN-beta, IRF-2 and TNF-alpha
      transcripts increased upon viral infection. The IRF-1 mRNA was rapidly induced by
      IFN treatment and decreased after Sendai virus infection. Our results show that,
      in peripheral blood lymphocytes, IFN-alpha and -beta genes have a different
      response to IFN induction, thus suggesting different regulatory mechanisms for
      IFN induction of type I IFN genes in peripheral blood lymphocytes.

PMID- 9251760
TI  - Improved purification of transducin subunits from bovine retinal rod outer
      segments.
AB  - Transducin serves as a mediator between the receptor protein, rhodopsin, and the
      effector protein, cGMP phosphodiesterase, in the visual process. Transducin is a
      protein composed of three polypeptides: T alpha, T beta, and T gamma, and acts as
      two functional units, the alpha-subunit and the beta gamma-complex. In the
      present study, I describe an efficient and fast method of purifying T alpha and T
      beta gamma using chromatography on a blue agarose column connected in tandem with
      an omega-amino octylagarose column. The recombination of T alpha and T beta gamma
      reconstitutes the functional heterotrimeric holoprotein, as demonstrated by the
      recovery of three native properties of transducin: 1) its capacity to exchange
      guanine nucleotide, 2) its GTP hydrolytic activity, and 3) the ADP-ribosylation
      of T alpha catalysed by pertussis toxin.

PMID- 9251761
TI  - Neuroendocrine regulation of salt and water metabolism.
AB  - Neurons which release atrial natriuretic peptide (ANPergic neurons) have their
      cell bodies in the paraventricular nucleus and in a region extending rostrally
      and ventrally to the anteroventral third ventricular (AV3V) region with axons
      which project to the median eminence and neural lobe of the pituitary gland.
      These neurons act to inhibit water and salt intake by blocking the action of
      angiotensin II. They also act, after their release into hypophyseal portal
      vessels, to inhibit stress-induced ACTH release, to augment prolactin release,
      and to inhibit the release of LHRH and growth hormone-releasing hormone.
      Stimulation of neurons in the AV3V region causes natriuresis and an increase in
      circulating ANP, whereas lesions in the AV3V region and caudally in the median
      eminence or neural lobe decrease resting ANP release and the response to blood
      volume expansion. The ANP neurons play a crucial role in blood volume expansion
      induced release of ANP and natriuresis since this response can be blocked by
      intraventricular (3V) injection of antisera directed against the peptide. Blood
      volume expansion activates baroreceptor input via the carotid, aortic and renal
      baroreceptors, which provides stimulation of noradrenergic neurons in the locus
      coeruleus and possibly also serotonergic neurons in the raphe nuclei. These
      project to the hypothalamus to activate cholinergic neurons which then stimulate
      the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the
      paraventricular and supraoptic nuclei to release oxytocin from the neural lobe
      which circulates to the atria to stimulate the release of ANP. ANP causes a rapid
      reduction in effective circulating blood volume by releasing cyclic GMP which
      dilates peripheral vessels and also acts within the heart to slow its rate and
      atrial force of contraction. The released ANP circulates to the kidney where it
      acts through cyclic GMP to produce natriuresis and a return to normal blood
      volume.

PMID- 9251762
TI  - A novel polymorphism in the coding region of the vasopressin type 2 receptor
      gene.
AB  - Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by renal
      inability to respond properly to arginine vasopressin due to mutations in the
      vasopressin type 2 receptor (V2(R)) gene in affected kindreds. In most kindreds
      thus far reported, the mode of inheritance follows an X chromosome-linked
      recessive pattern although autosomal-dominant and autosomal-recessive modes of
      inheritance have also been described. Studies demonstrating mutations in the
      V2(R) gene in affected kindreds that modify the receptor structure, resulting in
      a dys- or nonfunctional receptor have been described, but phenotypically
      indistinguishable NDI patients with a structurally normal V2(R) gene have also
      been reported. In the present study, we analyzed exon 3 of the V2(R) gene in 20
      unrelated individuals by direct sequencing. A C-->T alteration in the third
      position of codon 331 (AGC-->AGT), which did not alter the encoded amino acid,
      was found in nine individuals, including two unrelated patients with NDI. Taken
      together, these observations emphasize the molecular heterogeneity of a
      phenotypically homogeneous syndrome.

PMID- 9251763
TI  - Vasopressor mechanisms in acute aortic coarctation hypertension.
AB  - Angiotensin II (ANG II) and vasopressin (AVP) act together with the mechanical
      effect of aortic constriction in the onset of acute aortic coarctation
      hypertension. Blockade of ANG II and AVP V1 receptors demonstrated that ANG II
      acts on the prompt (5 min) rise in pressure whereas AVP is responsible for the
      maintenance (30-45 min) of the arterial pressure elevation during aortic
      coarctation. Hormone assays carried out on blood collected from conscious rats
      submitted to aortic constriction supported a role for ANG II in the early stage
      and a combined role for both ANG II and AVP in the maintenance of proximal
      hypertension. As expected, a role for catecholamines was ruled out in this model
      of hypertension, presumably due to the inhibitory effect of the sinoaortic
      baroreceptors. The lack of afferent feedback from the kidneys for AVP release
      from the central nervous system in rats with previous renal denervation allowed
      ANG II to play the major role in the onset of the hypertensive response. Median
      eminence-lesioned rats exhibited a prompt increase in proximal pressure followed
      by a progressive decline to lower hypertensive levels, revealing a significant
      role for the integrity of the neuroaxis in the maintenance of the aortic
      coarctation hypertension through the release of AVP. In conclusion, the important
      issue raised by this model of hypertension is the likelihood of a link between
      some vascular territory-probably renal-below the coarctation triggering the
      release of AVP, with this vasoconstrictor hormone participating with Ang II and
      the mechanical effect of aortic constriction in the acute aortic coarctation
      hypertension.

PMID- 9251764
TI  - Interaction between NO and oxytocin: influence on LHRH release.
AB  - Nitric oxide synthase (NOS)-containing neurons have been localized in various
      parts of the CNS. These neurons occur in the hypothalamus, mostly in the
      paraventricular and supraoptic nuclei and their axons project to the neural lobe
      of the pituitary gland. We have found that nitric oxide (NO) controls luteinizing
      hormone-releasing hormone (LHRH) release from the hypothalamus acting as a signal
      transducer in norepinephrine (NE)-induced LHRH release. LHRH not only releases LH
      from the pituitary but also induces sexual behavior. On the other hand, it is
      known that oxytocin also stimulates mating behavior and there is some evidence
      that oxytocin can increase NE release. Therefore, it occurred to us that oxytocin
      may also stimulate LHRH release via NE and NO. To test this hypothesis, we
      incubated medial basal hypothalamic (MBH) explants from adult male rats in vitro.
      Following a preincubation period of 30 min, MBH fragments were incubated in Krebs
      Ringer bicarbonate buffer in the presence of various concentrations of oxytocin.
      Oxytocin released LHRH at concentrations ranging from 0.1 nM to 1 microM with a
      maximal stimulatory effect (P < 0.001) at 0.1 microM, but with no stimulatory
      effect at 10 microM. That these effects were mediated by NO was shown by the fact
      that incubation of the tissues with NG-monomethyl-L-arginine (NMMA), a
      competitive inhibitor of NOS, blocked the stimulatory effects. Furthermore, the
      release of LHRH by oxytocin was also blocked by prazocin, an alpha 1-adrenergic
      receptor antagonist, indicating that NE mediated this effect. Oxytocin at the
      same concentrations also increased the activity of NOS (P < 0.01) as measured by
      the conversion of [14C]arginine to citrulline, which is produced in equimolar
      amounts with NO by the action of NOS. The release of LHRH induced by oxytocin was
      also accompanied by a significant (P < 0.02) increase in the release of
      prostaglandin E2 (PGE2), a mediator of LHRH release that is released by NO. On
      the other hand, incubation of neural lobes with various concentrations of sodium
      nitroprusside (NP) (300 or 600 microM), a releaser of NO, revealed that NO acts
      to suppress (P < 0.01) the release of oxytocin. Therefore, our results indicate
      that oxytocin releases LHRH by stimulating NOS via NE, resulting in an increased
      release of NO, which increases PGE2 release that in turn induces LHRH release.
      Furthermore, the released NO can act back on oxytocinergic terminals to suppress
      the release of oxytocin in an ultrashort-loop negative feedback.

PMID- 9251765
TI  - Does plasma ANP participate in natriuresis induced by alpha-MSH?
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH; 0.6 and 3 nmol) micro-injected
      into the anteroventral region of the third ventricle (AV3V) induced a significant
      increase in diuresis without modifying natriuresis or kaliuresis. Intraperitoneal
      (ip) injection of alpha-MSH (3 and 9.6 nmol) induced a significant increase in
      urinary sodium, potassium and water excretion. Intraperitoneal (3 and 4.8 nmol)
      or iv (3 and 9.6 nmol) administration of alpha-MSH did not induce any significant
      changes in plasma atrial natriuretic peptide (ANP), suggesting that the
      natriuresis, kaliuresis and diuresis induced by the systemic action of alpha-MSH
      can be dissociated from the increase in plasma ANP. These preliminary results
      suggest that alpha-MSH may be involved in a gamma-MSH-independent mechanism of
      regulation of hydromineral metabolism.

PMID- 9251766
TI  - Atrial natriuretic peptide and feeding activity patterns in rats.
AB  - This review presents historical data about atrial natriuretic peptide (ANP) from
      its discovery as an atrial natriuretic factor (ANF) to its role as an atrial
      natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic
      pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the
      rat. Food restriction proved to be an interesting model to investigate this
      relationship. The role of ANP must be understood within a context of peripheral
      and central interactions involving different peptides and pathways.

PMID- 9251767
TI  - Interactions of ANP and ANG II in tubular nephron acidification.
AB  - In order to examine the effects and the interaction of angiotensin II (ANG II, 1
      pM) and atrial natriuretic peptide (ANP, 1 microM) on the kinetics of bicarbonate
      reabsorption in the rat middle proximal tubule, we performed in vivo experiments
      using a stopped-flow microperfusion technique with the determination of lumen pH
      by Sb microelectrodes. These studies confirmed that ANG II added to the luminal
      or peritubular capillary perfusion fluid stimulates proximal bicarbonate
      reabsorption and showed that ANP alone does not affect this process, but impairs
      the stimulation caused by ANG II. We also studied the effects and the interaction
      of these hormones in cortical distal nephron acidification. Bicarbonate
      reabsorption was evaluated by the acidification kinetic technique in early (ED)
      and late (LD) distal tubules in rats during in vivo stopped-flow microperfusion
      experiments. The intratubular pH was measured with a double-barreled
      microelectrode with H(+)-sensitive resin. The results indicate that ANG II acted
      by stimulating Na+/H+ exchange in ED (81%) and LD (54%) segments via activation
      of AT1 receptors, as well as vacuolar H(+)-ATPase in LD segments (33%). ANP did
      not affect bicarbonate reabsorption in either segment and, as opposed to what was
      seen in the proximal tubule, did not impair the stimulation caused by ANG II. To
      investigate the mechanism of action of these hormones in more detail, we studied
      cell pH dependence on ANG II and ANP in MDCK cells using the fluorescent probe
      BCECF. We showed that the velocity of cell pH recovery was almost abolished in
      the absence of Na+, indicating that it is dependent on Na+/H+ exchange. ANP (1
      microM) alone had no effect on this recovery but reversed both the acceleration
      of H+ extrusion at low ANG II levels (1 pM and 1 nM), and inhibition of H+
      extrusion at higher ANG II levels (100 nM). To obtain more information on the
      mechanism of interaction of these hormones, we also studied their effects on the
      regulation of intracellular free calcium concentration, [Ca2+]i, monitored with
      the fluorescent probe Fura-2 in MDCK cells in suspension. The data indicate that
      the addition of increasing concentrations of ANG II (1 pM to 1 microM) to the
      cell suspension led to a progressive increase in [Ca2+]i to 2-3 times the basal
      level. In contrast, the addition of ANP (1 microM) to the cell suspension led to
      a very rapid 60% decrease in [Ca2+]i and reduced the increase elicited by ANG II,
      thus modulating the effect of ANG II on [Ca2+]i. These results may indicate a
      role of [Ca2+]i in the regulation of the H+ extrusion process mediated by Na+/H+
      exchange and stimulated/impaired by ANG II. The data are compatible with
      stimulation of Na+/H+ exchange by increases of [Ca2+]i in the lower range, and
      inhibition at high [Ca2+]i levels.

PMID- 9251768
TI  - Regulation of nephron acidification by corticosteroids.
AB  - The present paper reviews work from our laboratories evaluating the importance of
      adrenal cortical hormones in acidification by proximal and cortical distal
      tubules. Proximal acidification was determined by stationary microperfusion, and
      measurement of bicarbonate reabsorption using luminal pH determination was
      performed with H(+)-ionsensitive microelectrodes. Rats were adrenalectomized
      (ADX) 48 h before the experiments, and corticosteroids (aldosterone (A),
      corticosterone (B), and 18-OH corticosterone (18-OH-B)) were injected
      intramuscularly 100 and 40 min before the experiments. In ADX rats stationary pH
      increased significantly to 7.03 as compared to sham-operated rats (6.78).
      Bicarbonate reabsorption decreased from 2.65 +/- 0.18 in sham-operated rats to
      0.50 +/- 0.07 nmol cm-2 s-1 after ADX. The administration of the three hormones
      stimulated proximal tubule acidification, reaching, however, only 47.2% of the
      sham values in aldosterone-treated rats. Distal nephron acidification was studied
      by measuring urine minus blood pCO2 differences (U-B pCO2) in bicarbonate-loaded
      rats treated as above. This pCO2 difference is used as a measure of the distal
      nephron ability to secrete H+ ions into an alkaline urine. U-B pCO2 decreased
      significantly from 39.9 +/- 1.26 to 11.9 +/- 1.99 mmHg in ADX rats. When
      corticosteroids were given to ADX rats before the experiment, U-B pCO2 increased
      significantly, but reached control levels only when aldosterone (two 3-microgram
      doses per rat) plus corticosterone (220 micrograms) were given together. In order
      to control for the effect of aldosterone on distal transepithelial potential
      difference one group of rats was treated with amiloride, which blocks distal
      sodium channels. Amiloride-treated rats still showed a significant reduction in U
      B pCO2 after ADX. Only corticosterone and 18-OH-B but not aldosterone increased U
      B pCO2 back to the levels of sham-operated rats. These results show that
      corticosteroids stimulate renal tubule acidification both in proximal and distal
      nephrons and provide some clues about the mechanism of action of these steroids.

PMID- 9251769
TI  - The interaction of meal-related, rhythmic and homeostatic mechanisms and the
      generation of thirst and drinking.
AB  - One of the primary goals of the study of thirst is to understand why drinking
      occurs under ad libitum or natural conditions. An appreciation of the
      experimental strategies applied by physiologists studying thirst from different
      perspectives can facilitate progress toward understanding the natural history of
      drinking behavior. Drinking research carried out using three separate
      perspectives-homeostatic, circadian rhythms, and food-associated-generates types
      of information about the mechanisms underlying drinking behavior. By combining
      research strategies and methods derived from each of these approaches, it has
      been possible to gain new information that increases our appreciation of the
      interactions between homeostatic mechanisms and circadian rhythms in the
      modulation of water intake and how these might be related to drinking associated
      with food intake under near natural conditions.

PMID- 9251770
TI  - Functional evidence that the central renin-angiotensin system plays a role in the
      pressor response induced by central injection of carbachol.
AB  - We investigated the effects of losartan, an AT1-receptor blocker, and ramipril, a
      converting enzyme inhibitor, on the pressor response induced by angiotensin II
      (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250
      300 g) with a stainless steel cannula implanted into the lateral ventricle (LV)
      were used. The injection of losartan (50 nmol/1 microliter) into the LV blocked
      the pressor response induced by ANG II (12 ng/1 microliter) and carbachol (2
      nmol/1 microliter). After injection of ANG II and carbachol into the LV, mean
      arterial pressure (MAP) increased to 31 +/- 1 and 28 +/- 2 mmHg, respectively.
      Previous injection of losartan abolished the increase in MAP induced by ANG II
      and carbachol into the LV (2 +/- 1 and 5 +/- 2 mmHg, respectively). The injection
      of ramipril (12 ng/1 microliter) prior to carbachol blocked the pressor effect of
      carbachol to 7 +/- 3 mmHg. These results suggest an interaction between central
      cholinergic pathways and the angiotensinergic system in the regulation of
      arterial blood pressure.

PMID- 9251771
TI  - Multifactorial control of water and saline intake: role of alpha 2-adrenoceptors.

PMID- 9251772
TI  - Renal actions of angiotensin-(1-7).
AB  - The heptapeptide angiotensin-(1-7) is considered to be a biologically active
      endproduct of the renin-angiotensin system. This angiotensin, which is devoid of
      the most known actions of angiotensin II such as induction of drinking behavior
      and vasoconstriction, has several selective effects in the brain and periphery.
      In the present article we briefly review recent evidence for a physiological role
      of angiotensin-(1-7) in the control of hydroelectrolyte balance.

PMID- 9251773
TI  - The myth of nitric oxide in central cardiovascular control by the nucleus tractus
      solitarii.
AB  - Considerable evidence suggests that nitroxidergic mechanisms in the nucleus
      tractus solitarii (NTS) participate in cardiovascular reflex control. Much of
      that evidence, being based on responses to nitric oxide precursors or inhibitors
      of nitric oxide synthesis, has been indirect and circumstantial. We sought to
      directly determine cardiovascular responses to nitric oxide donors microinjected
      into the NTS and to determine if traditional receptor mechanisms might account
      for responses to certain of these donors in the central nervous system.
      Anesthetized adult Sprague Dawley rats that were instrumented for recording
      arterial pressure and heart rate were used in the physiological studies.
      Microinjection of nitric oxide itself into the NTS did not produce any
      cardiovascular responses and injection of sodium nitroprusside elicited minimal
      depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO), S
      nitrosoacetylpenicillamine (SNAP), and S-nitroso-D-cysteine (D-SNC) produced no
      significant cardiovascular responses while injection of S-nitroso-L-cysteine (L
      SNC) elicited brisk, dose-dependent depressor and bradycardic responses. In
      contrast, injection of glyceryl trinitrate elicited minimal pressor responses
      without associated changes in heart rate. It is unlikely that the responses to L
      SNC were dependent on release of nitric oxide in that 1) the responses were not
      affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis
      prior to injection of L-SNC and 2) L- and D-SNC released identical amounts of
      nitric oxide when exposed to brain tissue homogenates. Although GSNO did not
      independently affect blood pressure, its injection attenuated responses to
      subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested
      that in rat brain synaptosomes there is a saturable binding site for GSNO that is
      displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine,
      not nitric oxide, may be an interneuronal messenger for cardiovascular neurons in
      the NTS.

PMID- 9251774
TI  - Neural reflex regulation of arterial pressure in pathophysiological conditions:
      interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex.
AB  - The maintenance of arterial pressure at levels adequate to perfuse the tissues is
      a basic requirement for the constancy of the internal environment and survival.
      The objective of the present review was to provide information about the basic
      reflex mechanisms that are responsible for the moment-to-moment regulation of the
      cardiovascular system. We demonstrate that this control is largely provided by
      the action of arterial and non-arterial reflexes that detect and correct changes
      in arterial pressure (baroreflex), blood volume or chemical composition (mechano-
      and chemosensitive cardiopulmonary reflexes), and changes in blood-gas
      composition (chemoreceptor reflex). The importance of the integration of these
      cardiovascular reflexes is well understood and it is clear that processing mainly
      occurs in the nucleus tractus solitarii, although the mechanism is poorly
      understood. There are several indications that the interactions of baroreflex,
      chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system
      control the activity of autonomic preganglionic neurons through parallel afferent
      and efferent pathways to achieve cardiovascular homeostasis. It is surprising
      that so little appears in the literature about the integration of these neural
      reflexes in cardiovascular function. Thus, our purpose was to review the
      interplay between peripheral neural reflex mechanisms of arterial blood pressure
      and blood volume regulation in physiological and pathophysiological states.
      Special emphasis is placed on the experimental model of arterial hypertension
      induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of
      these three reflexes is demonstrable.

PMID- 9251775
TI  - Autonomic processing of the cardiovascular reflexes in the nucleus tractus
      solitarii.
AB  - The nucleus tractus solitarii (NTS) receives afferent projections from the
      arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and
      as a function of this information produces autonomic adjustments in order to
      maintain arterial blood pressure within a narrow range of variation. The
      activation of each of these cardiovascular afferents produces a specific
      autonomic response by the excitation of neuronal projections from the NTS to the
      ventrolateral areas of the medulla (nucleus ambiguous, caudal and rostal
      ventrolateral medulla). The neurotransmitters at the NTS level as well as the
      excitatory amino acid (EAA) receptors involved in the processing of the autonomic
      responses in the NTS, although extensively studied, remain to be completely
      elucidated. In the present review we discuss the role of the EAA L-glutamate and
      its different receptor subtypes in the processing of the cardiovascular reflexes
      in the NTS. The data presented in this review related to the neurotransmission in
      the NTS are based on experimental evidence obtained in our laboratory in
      unanesthetized rats. The two major conclusions of the present review are that a)
      the excitation of the cardiovagal component by cardiovascular reflex activation
      (chemo- and Bezold-Jarisch reflexes) or by L-glutamate microinjection into the
      NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho
      excitatory component of the chemoreflex and the pressor response to L-glutamate
      microinjected into the NTS are not affected by the NMDA receptors antagonist,
      suggesting that the sympatho-excitatory component of these responses is mediated
      by non-NMDA receptors.

PMID- 9251776
TI  - Effects of ouabain on vascular reactivity.
AB  - Ouabain is an endogenous substance occurring in the plasma in the nanomolar
      range, that has been proposed to increase vascular resistance and induce
      hypertension. This substance acts on the alpha-subunit of Na+,K(+)-ATPase
      inhibiting the Na(+)-pump activity. In the vascular smooth muscle this effect
      leads to intracellular Na+ accumulation that reduces the activity of the Na+/Ca2+
      exchanger and to an increased vascular tone. It was also suggested that
      circulating ouabain, even in the nanomolar range, sensitizes the vascular smooth
      muscle to vasopressor substances. We tested the latter hypothesis by studying the
      effects of ouabain in the micromolar and nanomolar range on phenylephrine (PE)
      evoked pressor responses. The experiments were performed in normotensive and
      hypertensive rats in vivo, under anesthesia, and in perfused rat tail vascular
      beds. The results showed that ouabain pretreatment increased the vasopressor
      responses to PE in vitro and in vivo. This sensitization after ouabain treatment
      was also observed in hypertensive animals which presented an enhanced vasopressor
      response to PE in comparison to normotensive animals. It is suggested that
      ouabain at nanomolar concentrations can sensitize vascular smooth muscle to
      vasopressor stimuli possibly contributing to increased tone in hypertension.

PMID- 9251778
TI  - Simulations of nucleation and early growth stages of protein crystals.
AB  - Analysis of known protein crystal structures reveals that interaction energies
      between monomer pairs alone are not sufficient to overcome entropy loss related
      to fixing monomers in the crystal lattice. Interactions with several neighbors in
      the crystal are required for stabilization of monomers in the lattice. A
      microscopic model of nucleation and early growth stages of protein crystals,
      based on the above observations, is presented. Anisotropy of protein molecules is
      taken into account by assigning free energies of association (proportional to the
      buried surface area) to individual monomer-monomer contacts in the lattice.
      Lattice simulations of the tetragonal lysozyme crystal based on the model
      correctly reproduce structural features of the movement of dislocation on the
      (110) crystal face. The dislocation shifts with the speed equal to the one
      determined experimentally if the geometric probability of correct orientation is
      set to 10(-5), in agreement with previously published estimates. At this value of
      orientational probability, the first nuclei, the critical size of which for
      lysozyme is four monomers, appear in 1 ml of supersaturated solution on a time
      scale of microseconds. Formation of the ordered phase proceeds through the growth
      of nuclei (rather then their association) and requires nucleations on the surface
      at certain stages.

PMID- 9251777
TI  - Binding of the estrogen receptor to DNA. The role of waters.
AB  - Molecular dynamics simulations are carried out to investigate the binding of the
      estrogen receptor, a member of the nuclear hormone receptor family, to specific
      and non-specific DNA. Two systems have been simulated, each based on the
      crystallographic structure of a complex of a dimer of the estrogen receptor DNA
      binding domain with DNA. One structure includes the dimer and a consensus segment
      of DNA, ds(CCAGGTCACAGTGACCTGG); the other structure includes the dimer and a
      nonconsensus segment of DNA, ds(CCAGAACACAGTGACCTGG). The simulations involve an
      atomic model of the protein-DNA complex, counterions, and a sphere of explicit
      water with a radius of 45 A. The molecular dynamics package NAMD was used to
      obtain 100 ps of dynamics for each system with complete long-range electrostatic
      interactions. Analysis of the simulations revealed differences in the protein-DNA
      interactions for consensus and nonconsensus sequences, a bending and unwinding of
      the DNA, a slight rearrangement of several amino acid side chains, and inclusion
      of water molecules at the protein-DNA interface region. Our results indicate that
      binding specificity and stability is conferred by a network of direct and water
      mediated protein-DNA hydrogen bonds. For the consensus sequence, the network
      involves three water molecules, residues Glu-25, Lys-28, Lys-32, Arg-33, and
      bases of the DNA. The binding differs for the nonconsensus DNA sequence in which
      case the fluctuating network of hydrogen bonds allows water molecules to enter
      the protein-DNA interface. We conclude that water plays a role in furnishing DNA
      binding specificity to nuclear hormone receptors.

PMID- 9251779
TI  - The pore-lining region of shaker voltage-gated potassium channels: comparison of
      beta-barrel and alpha-helix bundle models.
AB  - Although there is a large body of site-directed mutagenesis data that identify
      the pore-lining sequence of the voltage-gated potassium channel, the structure of
      this region remains unknown. We have interpreted the available biochemical data
      as a set of topological and orientational restraints and employed these
      restraints to produce molecular models of the potassium channel pore region, H5.
      The H5 sequence has been modeled either as a tetramer of membrane-spanning beta
      hairpins, thus producing an eight-stranded beta-barrel, or as a tetramer of
      incompletely membrane-spanning alpha-helical hairpins, thus producing an eight
      staved alpha-helix bundle. In total, restraints-directed modeling has produced 40
      different configurations of the beta-barrel model, each configuration comprising
      an ensemble of 20 structures, and 24 different configurations of the alpha-helix
      bundle model, each comprising an ensemble of 24 structures. Thus, over 1300 model
      structures for H5 have been generated. Configurations have been ranked on the
      basis of their predicted pore properties and on the extent of their agreement
      with the biochemical data. This ranking is employed to identify particular
      configurations of H5 that may be explored further as models of the pore-lining
      region of the voltage-gated potassium channel pore.

PMID- 9251780
TI  - Molecular motions within the pore of voltage-dependent sodium channels.
AB  - The pores of ion channel proteins are often modeled as static structures. In this
      view, selectivity reflects rigidly constrained backbone orientations. Such a
      picture is at variance with the generalization that biological proteins are
      flexible, capable of major internal motions on biologically relevant time scales.
      We tested for motions in the sodium channel pore by systematically introducing
      pairs of cysteine residues throughout the pore-lining segments. Two distinct
      pairs of residues spontaneously formed disulfide bonds bridging domains I and II.
      Nine other permutations, involving all four domains, were capable of disulfide
      bonding in the presence of a redox catalyst. The results are inconsistent with a
      single fixed backbone structure for the pore; instead, the segments that line the
      permeation pathway appear capable of sizable motions.

PMID- 9251781
TI  - Protein stability and conformational rearrangements in lipid bilayers: linear
      gramicidin, a model system.
AB  - The replacement of four tryptophans in gramicidin A by four phenylalanines
      (gramicidin M) causes no change in the molecular fold of this dimeric peptide in
      a low dielectric isotropic organic solvent, but the molecular folds are
      dramatically different in a lipid bilayer environment. The indoles of gramicidin
      A interact with the anisotropic bilayer environment to induce a change in the
      molecular fold. The double-helical fold of gramicidin M, as opposed to the single
      stranded structure of gramicidin A, is not compatible with ion conductance.
      Gramicidin A/gramicidin M hybrid structures have also been prepared, and like
      gramicidin M homodimers, these dimeric hybrids appear to have a double-helical
      fold, suggesting that a couple of indoles are being buried in the bilayer
      interstices. To achieve this equilibrium structure (i.e., minimum energy
      conformation), incubation at 68 degrees C for 2 days is required. Kinetically
      trapped metastable structures may be more common in lipid bilayers than in an
      aqueous isotropic environment. Structural characterizations in the bilayers were
      achieved with solid-state NMR-derived orientational constraints from uniformly
      aligned lipid bilayer samples, and characterizations in organic solvents were
      accomplished by solution NMR.

PMID- 9251782
TI  - Stability and dynamics of G-actin: back-door water diffusion and behavior of a
      subdomain 3/4 loop.
AB  - Molecular dynamics simulations have been performed on solvated G-actin bound to
      ADP and ATP, starting with the crystal structure of the actin-DNase 1 complex,
      including a Ca2+ or Mg2+ ion at the high-affinity divalent cation-binding site.
      Water molecules have been found to enter the nucleotide-binding site (phosphate
      vicinity) along two pathways, from the side where the nucleotide base is exposed
      to water, as well as from the opposite side. The water channels suggest a "back
      door" mechanism for ATP hydrolysis in which the phosphate is released to a side
      opposite that of nucleotide binding and unbinding. The simulations also reveal a
      propensity of G-actin to alter its crystallographic structure toward the
      filamentous structure. Domain movement closes the nucleotide cleft, the movement
      being more pronounced for bound Mg2+. The conformational change is interpreted as
      a response of the system to missing water molecules in the crystal structure. The
      structures arising in the simulations, classified according to nucleotide cleft
      separation and radius of gyration of the protein, fall into two distinct
      clusters: a cluster of states that are similar to the G-actin crystal structure,
      and a cluster of states with small cleft separation and with the subdomain 3/4
      loop 264-273 detached from the protein. The latter states resemble the putative
      filamentous structure of actin, in which the loop connects the two strands of the
      actin filament.

PMID- 9251784
TI  - Scanning ion conductance microscopy of living cells.
AB  - Currently there is a great interest in using scanning probe microscopy to study
      living cells. However, in most cases the contact the probe makes with the soft
      surface of the cell deforms or damages it. Here we report a scanning ion
      conductance microscope specially developed for imaging living cells. A key
      feature of the instrument is its scanning algorithm, which maintains the working
      distance between the probe and the sample such that they do not make direct
      physical contact with each other. Numerical simulation of the probe/sample
      interaction, which closely matches the experimental observations, provides the
      optimum working distance. The microscope scans highly convoluted surface
      structures without damaging them and reveals the true topography of cell
      surfaces. The images resemble those produced by scanning electron microscopy,
      with the significant difference that the cells remain viable and active. The
      instrument can monitor small-scale dynamics of cell surfaces as well as whole
      cell movement.

PMID- 9251783
TI  - Does TATA matter? A structural exploration of the selectivity determinants in its
      complexes with TATA box-binding protein.
AB  - The binding of the TATA box-binding protein (TBP) to a TATA sequence in DNA is
      essential for eukaryotic basal transcription. TBP binds in the minor groove of
      DNA, causing a large distortion of the DNA helix. Given the apparent
      stereochemical equivalence of AT and TA basepairs in the minor groove, DNA
      deformability must play a significant role in binding site selection, because not
      all AT-rich sequences are bound effectively by TBP. To gain insight into the
      precise role that the properties of the TATA sequence have in determining the
      specificity of the DNA substrates of TBP, the solution structure and dynamics of
      seven DNA dodecamers have been studied by using molecular dynamics simulations.
      The analysis of the structural properties of basepair steps in these TATA
      sequences suggests a reason for the preference for alternating pyrimidine-purine
      (YR) sequences, but indicates that these properties cannot be the sole
      determinant of the sequence specificity of TBP. Rather, recognition depends on
      the interplay between the inherent deformability of the DNA and steric
      complementarity at the molecular interface.

PMID- 9251785
TI  - A realistic model of biphasic calcium transients in electrically nonexcitable
      cells.
AB  - In many electrically nonexcitable cells, the release of calcium from internal
      stores is followed by a much slower phase in which the intracellular calcium
      concentration decreases gradually to a sustained value higher than the
      concentration before stimulation. This elevated calcium plateau has been shown to
      be the result of calcium influx. The model presented in this work describes a
      system consisting of a cytoplasmic calcium store and a plasma membrane calcium
      channel, both excitable by a membrane receptor; a fast cytoplasmic calcium
      buffer; and calcium pumps in both the calcium store and cellular membranes.
      Inherent difficulties in the numerical evaluation of the model, caused by very
      large calcium fluxes across the store membrane, were overcome by analytically
      separating the fast processes of calcium release from the slower processes of
      calcium cycling across the plasma membrane. This enabled the simulation of
      realistic biphasic calcium transients similar to those observed experimentally.
      The model predicted 1) a strong correlation between the rate of calcium cycling
      across the plasma membrane and the rate of calcium decay; and 2) a dependence on
      the level of cell excitation of the maximum rise in cytoplasmic calcium
      concentration, the level of the elevated calcium plateau, and the rate of calcium
      decay. Using the model, we simulated the washout of agonist from the bathing
      solution and the depletion of the calcium store by a pharmacological agent (such
      as thapsigargin) under several experimental conditions.

PMID- 9251786
TI  - Theoretical considerations on the role of membrane potential in the regulation of
      endosomal pH.
AB  - Na+,K(+)-ATPase has been observed to partially inhibit acidification of early
      endosomes by increasing membrane potential, whereas chloride channels have been
      observed to enhance acidification in endosomes and lysosomes. However, little
      theoretical analysis of the ways in which different pumps and channels may
      interact has been carried out. We therefore developed quantitative models of
      endosomal pH regulation based on thermodynamic considerations. We conclude that
      1) both size and shape of endosomes will influence steady-state endosomal pH
      whenever membrane potential due to the pH gradient limits proton pumping, 2)
      steady-state pH values similar to those observed in early endosomes of living
      cells can occur in endosomes containing just H(+)-ATPases and Na+,K(+)-ATPases
      when low endosomal buffering capacities are present, and 3) inclusion of active
      chloride channels results in predicted pH values well below those observed in
      vivo. The results support the separation of endocytic compartments into two
      classes, those (such as early endosomes) whose acidification is limited by
      attainment of a certain membrane potential, and those (such as lysosomes) whose
      acidification is limited by the attainment of a certain pH. The theoretical
      framework and conclusions described are potentially applicable to other membrane
      enclosed compartments that are acidified, such as elements of the Golgi
      apparatus.

PMID- 9251787
TI  - Deriving reaction mechanisms from kinetic spectroscopy. Application to late
      rhodopsin intermediates.
AB  - A general algebraic approach to the kinetic analysis of time-dependent absorption
      data is presented that allows the calculation of possible kinetic schemes. The
      kinetic matrices of all possible reaction mechanisms are calculated from
      experimental eigenvalues and eigenvectors derived from the decay constants and
      amplitude spectra (b-spectra) of the global exponential fit to the time
      dependence of the absorption data. The eigenvalues are directly related to the
      decay constants, and the eigenvectors are obtained by decomposing the b-spectra
      into spectral components representing the intermediates. The analysis method is
      applied to the late intermediates (lumi, meta I, meta I-380, and meta II) of the
      rhodopsin photoreaction. The b-spectra are decomposed into lumi, meta I, meta
      380, and rhodopsin spectra. The meta-380 component is partitioned into
      isospectral meta I-380 and meta II components based on physical criteria. The
      calculated kinetic matrices yield a number of reaction mechanisms (linear scheme
      with back reactions, branched schemes with equilibrium steps, and a variety of
      square models) consistent with the photolysis data at 25 degrees C. The problems
      associated with isospectral intermediates (meta I-380 and meta II) are treated
      successfully with this method.

PMID- 9251788
TI  - Protein turbines. I: The bacterial flagellar motor.
AB  - The bacterial flagellar motor is driven by a flux of ions between the cytoplasm
      and the periplasmic lumen. Here we show how an electrostatic mechanism can
      convert this ion flux into a rotary torque. We demonstrate that, with reasonable
      parameters, the model can reproduce many of the experimental measurements.

PMID- 9251789
TI  - SIMS: computation of a smooth invariant molecular surface.
AB  - SIMS, a new method of calculating a smooth invariant molecular dot surface, is
      presented. The SIMS method generates the smooth molecular surface by rolling two
      probe spheres. A solvent probe sphere is rolled over the molecule and produces a
      Richards-Connolly molecular surface (MS), which envelops the solvent-excluded
      volume of the molecule. In deep crevices, Connolly's method of calculating the MS
      has two deficiencies. First, it produces self-intersecting parts of the molecular
      surface, which must be removed to obtain the correct MS. Second, the correct MS
      is not smooth, i.e., the direction of the normal vector of the MS is not
      continuous, and some points of the MS are singular. We present an exact method
      for removing self-intersecting parts and smoothing the singular regions of the
      MS. The singular MS is smoothed by rolling a smoothing probe sphere over the
      inward side of the singular MS. The MS in the vicinity of singularities is
      replaced with the reentrant surface of the smoothing probe sphere. The smoothing
      method does not disturb the topology of a singular MS, and the smooth MS is a
      better approximation of the dielectric border between high dielectric solvent and
      the low dielectric molecular interior. The SIMS method generates a smooth
      molecular dot surface, which has a quasi-uniform dot distribution in two
      orthogonal directions on the molecular surface, which is invariant with molecular
      rotation and stable under changes in the molecular conformation, and which can be
      used in a variety of implicit methods of modeling solvent effects. The SIMS
      program is faster than the Connolly MS program, and in a matter of seconds
      generates a smooth dot MS of a 200-residue protein. The program is available from
      the authors on request (see http:@femto.med.unc.edu/SIMS).

PMID- 9251790
TI  - The monovalent cation "leak" transport in human erythrocytes: an electroneutral
      exchange process.
AB  - The mechanism of the "ground permeability" of the human erythrocyte membrane for
      K+ and Na+ was investigated with respect to a possible involvement of a
      previously unidentified specific transport pathway, because earlier studies
      showed that it cannot be explained on the basis of simple electrodiffusion. In
      particular, we analyzed and described the increase in the
      (ouabain+bumetanide+EGTA)-insensitive unidirectional K+ and Na+ influxes as well
      as effluxes (defined as "leak" fluxes) observed in erythrocytes suspended in low
      ionic-strength media. Using a carrier-type model and taking into account the
      influence of the ionic strength on the outer surface potential according to the
      Gouy-Chapman theory (i.e., the ion concentration near the membrane surface), we
      are able to describe the altered "leak" fluxes as an electroneutral process. In
      addition, we can show indirectly that this electroneutral flux is due to an
      exchange of monovalent cations with protons. This pathway is different from the
      amiloride-sensitive Na+/H+ exchanger present in the human red blood cell membrane
      and can be characterized as a K+(Na+)/H+ exchanger.

PMID- 9251791
TI  - The inner membrane barrier of lipid membranes experienced by the valinomycin/Rb+
      complex: charge pulse experiments at high membrane voltages.
AB  - The kinetic analysis of charge pulse experiments at planar lipid membranes in the
      presence of macrocyclic ion carriers has been limited so far to the low voltage
      range, where, under certain simplifying conditions, an analytical solution is
      available. In the present study, initial voltages of up to 300 mV were applied to
      the membrane, and the voltage decay through the conductive pathways of the
      membrane was followed as a function of time. The system of differential equations
      derived from the transport model was solved numerically and was compared with the
      experimental data. The generalized kinetic analysis of charge pulse experiments
      and of steady-state current-voltage curves was used to study the voltage
      dependence of the individual transport steps and to obtain information on the
      shape of the inner membrane barrier. The data were found to be consistent with a
      comparatively broad inner barrier such as a trapezoidal barrier or an image force
      barrier. The inner barrier was found to sense 70-76% of the voltage applied to
      the membrane. As a consequence, 24-30% of the voltage acts on the two interfacial
      barriers between membrane and water. The data refer to membranes formed from
      monoolein, monoeicosenoin, or monoerucin in n-decane.

PMID- 9251793
TI  - Intrinsic rectification of ion flux in alamethicin channels: studies with an
      alamethicin dimer.
AB  - Covalent dimers of alamethicin form conducting structures with gating properties
      that permit measurement of current-voltage (I-V) relationships during the
      lifetime of a single channel. These I-V curves demonstrate that the alamethicin
      channel is a rectifier that passes current preferentially, with voltages of the
      same sign as that of the voltage that induced opening of the channel. The degree
      of rectification depends on the salt concentration; single-channel I-V
      relationships become almost linear in 3 M potassium chloride. These properties
      may be qualitatively understood by using Poisson-Nernst-Planck theory and a
      modeled structure of the alamethicin pore.

PMID- 9251792
TI  - Species-specific voltage-gating properties of connexin-45 junctions expressed in
      Xenopus oocytes.
AB  - Gap junctions composed of connexin-45 (Cx45) homologs from four species,
      zebrafish, chicken, mouse, and human, were expressed in pairs of Xenopus oocytes.
      The macroscopic conductance (gj) of all Cx45 junctions was modulated by
      transjunctional voltage (Vj) and by the inside-outside voltage (Vm), and the
      modulation was species specific. Although their gating characteristics varied in
      voltage sensitivity and kinetics, the four Cx45 junctions shared 1) maximum
      conductance at Vj = 0 and symmetrical gj reduction in response to positive and
      negative Vj of low amplitude, with little residual conductance; and 2) gj
      increases in response to simultaneous depolarization of the paired cells. The
      formation of hybrid channels, comprising Cx45 hemichannels from different
      species, allowed us to infer that two separate gates exist, one in each
      hemichannel, and that each Cx45 hemichannel is closed by the negativity of Vj on
      its cytoplasmic side. Interestingly, the Vm dependence of hybrid channels also
      suggests the presence of two gates in series, one Vm gate in each hemichannel.
      Thus the Vj and Vm dependence provides evidence that two independent voltage
      gates in each Cx45 hemichannel exist, reacting through specific voltage sensors
      and operating by different mechanisms, properties that have evolved divergently
      among species.

PMID- 9251794
TI  - Differences in steady-state inactivation between Na channel isoforms affect local
      anesthetic binding affinity.
AB  - Cocaine and lidocaine are local anesthetics (LAs) that block Na currents in
      excitable tissues. Cocaine is also a cardiotoxic agent and can induce cardiac
      arrhythmia and ventricular fibrillation. Lidocaine is commonly used as a
      postinfarction antiarrhythmic agent. These LAs exert clinically relevant effects
      at concentrations that do not obviously affect the normal function of either
      nerve or skeletal muscle. We compared the cocaine and lidocaine affinities of
      human cardiac (hH1) and rat skeletal (mu 1) muscle Na channels that were
      transiently expressed in HEK 293t cells. The affinities of resting mu 1 and hH1
      channels were similar for cocaine (269 and 235 microM, respectively) and for
      lidocaine (491 and 440 microM, respectively). In addition, the affinities of
      inactivated mu 1 and hH1 channels were also similar for cocaine (12 and 10
      microM, respectively) and for lidocaine (19 and 12 microM, respectively). In
      contrast to previous studies, our results indicate that the greater sensitivity
      of cardiac tissue to cocaine or lidocaine is not due to a higher affinity of the
      LA receptor in cardiac Na channels, but that at physiological resting potentials
      (-100 to -90 mV), a greater percentage of hH1 channels than mu 1 channels are in
      the inactivated (i.e., high-affinity) state.

PMID- 9251795
TI  - Independent gating of single pores in CLC-0 chloride channels.
AB  - The Cl- channel from the Torpedo electric organ, CLC-0, is the prototype of a
      large gene family of Cl- channels. At the single-channel level, CLC-0 shows a
      "double-barreled" behavior. Recently it was shown that CLC-0 is a dimer, and it
      was suggested that each subunit forms a single pore. The two protopores are gated
      individually by a fast voltage and anion-dependent gating mechanism. A slower
      common gating mechanism operates on both pores simultaneously. Previously, wild
      type/mutant heteromeric channels had been constructed that display a large wild
      type pore and small mutant pore. Here we use patch-clamp recording of single wild
      type and mutant CLC-0 channels to investigate in detail the dependence of the
      gating of one protopore on the physically attached neighboring pore. No
      difference in rate constants of opening and closing of protopores could be found
      comparing homomeric wild-type and heteromeric wild-type/mutant channels. In
      addition, detailed kinetic analysis reveals that gating of single subunits is not
      correlated with the gating of the neighboring subunit. The results are consistent
      with the view that permeation and fast gating of individual pores are fully
      independent of the neighboring pore. Because the two subunits are associated in a
      common protein complex, opening and closing transitions of individual pores are
      probably due to only small conformational changes in each pore. In addition to
      the fast and slow gating mechanisms known previously for CLC-0, in the course of
      this study we occasionally observed an additional gating process that led to
      relatively long closures of single pores.

PMID- 9251796
TI  - Positive charges of the initial C-terminus domain of Cx32 inhibit gap junction
      gating sensitivity to CO2.
AB  - Gap junction channels close with CO2 exposure. To determine whether the carboxy
      terminus (CT) of connexin32 (Cx32) participates in gating, the CO2 sensitivity of
      channels made of Cx32 or Cx32 mutants was studied by double voltage clamp. In
      Xanopus laevis oocytes expressing Cx32, junctional conductance (Gj) dropped to
      85% and 47% of controls with 3- and 15-min CO2 exposures, respectively. In
      response to the 15-min exposure to CO2, pHi dropped to approximately 6.4 in 5-7
      min and did not decrease further, even with 30-min exposures. CT deletion by 84%
      did not affect CO2 sensitivity, but replacement of five arginines (R215, R219,
      R220, R223, and R224) with asparagines (N) or threonines at the beginning of CT
      (CT1) in Cx32 or Cx32 deleted beyond residue 225 greatly enhanced CO2 sensitivity
      (with 3-min CO2 Gj dropped to approximately 8%). Partial R/N replacement resulted
      in intermediate CO2 sensitivity enhancement. R215 is a stronger inhibitor than
      R219-220, whereas R223-224 may diminish the inhibitory efficiency of R215 and
      R219-220. Therefore, positive charges of CT1 reduce the CO2 sensitivity of Cx32,
      whereas the rest (> 80%) of CT seems to play no role in CO2-induced gating. The
      role of presumed electrostatic interactions among Cx32 domains in CO2-induced
      gating is discussed.

PMID- 9251797
TI  - Recovery of Ca2+ current, charge movements, and Ca2+ transients in myotubes
      deficient in dihydropyridine receptor beta 1 subunit transfected with beta 1
      cDNA.
AB  - The Ca2+ currents, charge movements, and intracellular Ca2+ transients of mouse
      dihydropyridine receptor (DHPR) beta 1-null myotubes expressing a mouse DHPR beta
      1 cDNA have been characterized. In beta 1-null myotubes maintained in culture for
      10-15 days, the density of the L-type current was approximately 7-fold lower than
      in normal cells of the same age (Imax was 0.65 +/- 0.05 pA/pF in mutant versus
      4.5 +/- 0.8 pA/pF in normal), activation of the L-type current was significantly
      faster (tau activation at +40 mV was 28 +/- 7 ms in mutant versus 57 +/- 8 ms in
      normal), charge movements were approximately 2.5-fold lower (Qmax was 2.5 +/- 0.2
      nC/microF in mutant versus 6.3 +/- 0.7 nC/microF in normal), Ca2+ transients were
      not elicited by depolarization, and spontaneous or evoked contractions were
      absent. Transfection of beta 1-null cells by lipofection with beta 1 cDNA
      reestablished spontaneous or evoked contractions in approximately 10% of cells
      after 6 days and approximately 30% of cells after 13 days. In contracting beta 1
      transfected myotubes there was a complete recovery of the L-type current density
      (Imax was 4 +/- 0.9 pA/pF), the kinetics of activation (tau activation at +40 mV
      was 64 +/- 5 ms), the magnitude of charge movements (Qmax was 6.7 +/- 0.4
      nC/microF), and the amplitude and voltage dependence of Ca2+ transients evoked by
      depolarizations. Ca2+ transients of transfected cells were unaltered by the
      removal of external Ca2+ or by the block of the L-type Ca2+ current,
      demonstrating that a skeletal-type excitation-contraction coupling was restored.
      The recovery of the normal skeletal muscle phenotype in beta 1-transfected beta
      null myotubes shows that the beta 1 subunit is essential for the functional
      expression of the DHPR complex.

PMID- 9251799
TI  - Pore formation and translocation of melittin.
AB  - Melittin, a bee venom, is a basic amphiphilic peptide, which mainly acts on the
      lipid matrix of membranes, lysing various cells. To elucidate the molecular
      mechanism, we investigated its interactions with phospholipid vesicles. The
      peptide formed a pore with a short lifetime in the membrane, as revealed by the
      release of an anionic fluorescent dye, calcein, from the liposomes. Our new
      double-labeling method clarified that the pore size increased with the peptide-to
      lipid ratio. Upon the disintegration of the pore, a fraction of the peptides
      translocated across the bilayer. The pore formation was coupled with the
      translocation, which was proved by three fluorescence experiments recently
      developed by our laboratory. A novel model for the melittin pore formation was
      discussed in comparison with other pore-forming peptides.

PMID- 9251798
TI  - The cytosolic inactivation domains of BKi channels in rat chromaffin cells do not
      behave like simple, open-channel blockers.
AB  - Most BK-type voltage- and Ca(2+)-dependent K+ channels in rat chromaffin cells
      exhibit rapid inactivation. This inactivation is abolished by brief trypsin
      application to the cytosolic face of membrane patches. Here we examine the
      effects of cytosolic channel blockade and pore occupancy on this inactivation
      process, using inside-out patches and whole-cell recordings. Occupancy of a
      superficial pore-blocking site by cytosolic quaternary blockers does not slow
      inactivation. Occupancy of a deeper pore-blocking site by cytosolic application
      of Cs+ is also without effect on the onset of inactivation. Although the rate of
      inactivation is relatively unaffected by changes in extracellular K+, the rate of
      recovery from inactivation (at -80 and -140 mV with 10 microM Ca2+) is faster
      with increases in extracellular K+ but is unaffected by the impermeant ion, Na+.
      When tail currents are compared after repolarization, either while channels are
      open or after inactivation, no channel reopening is detectable during recovery
      from inactivation. BK inactivation appears to be mechanistically distinct from
      that of other inactivating voltage-dependent channels. Although involving a
      trypsin-sensitive cytosolic structure, the block to permeation does not appear to
      occur directly at the cytosolic mouth or inner half of the ion permeation
      pathway.

PMID- 9251801
TI  - Effect of the dipole potential of a bilayer lipid membrane on gramicidin channel
      dissociation kinetics.
AB  - A technique of measuring of the light-induced transients of the gramicidin
      mediated electric current across a membrane in the presence of a photosensitizer
      has been applied for the study of the effect of agents modifying the dipole
      potential of a bilayer lipid membrane (phloretin, 6-ketocholestanol, and RH421)
      on the processes of the gramicidin channel dissociation and formation. It is
      shown that phloretin, known to lower the dipole potential, decelerates the flash
      induced decrease in the current, whereas 6-ketocholestanol and RH421, known to
      raise the dipole potential, accelerate the current decrease. It is revealed that
      the addition of phloretin leads to a decrease in the dissociation rate constant,
      whereas addition of either 6-ketocholestanol or RH421 causes an increase in this
      constant. Single-channel data show that phloretin brings about an increase in the
      lifetime of the gramicidin channels, whereas RH421 produces a more complicated
      effect. It is conclude that the dipole potential affects the process of channel
      dissociation, presumably via the influence on the movement of the dipoles of
      gramicidin molecules through the layer of the dipole potential drop near the
      membrane-water interface.

PMID- 9251800
TI  - Ionization, partitioning, and dynamics of tryptophan octyl ester: implications
      for membrane-bound tryptophan residues.
AB  - The presence of tryptophan residues as intrinsic fluorophores in most proteins
      makes them an obvious choice for fluorescence spectroscopic analyses of such
      proteins. Membrane proteins have been reported to have a significantly higher
      tryptophan content than soluble proteins. The role of tryptophan residues in the
      structure and function of membrane proteins has attracted a lot of attention.
      Tryptophan residues in membrane proteins and peptides are believed to be
      distributed asymmetrically toward the interfacial region. Tryptophan octyl ester
      (TOE) is an important model for membrane-bound tryptophan residues. We have
      characterized this molecule as a fluorescent membrane probe in terms of its
      ionization, partitioning, and motional characteristics in unilamellar vesicles of
      dioleoylphosphatidylcholine. The ionization property of this molecule in model
      membranes has been studied by utilizing its pH-dependent fluorescence
      characteristics. Analysis of pH-dependent fluorescence intensity and emission
      maximum shows that deprotonation of the alpha-amino group of TOE occurs with an
      apparent pKa of approximately 7.5 in the membrane. The fluorescence lifetime of
      membrane-bound TOE also shows pH dependence. The fluorescence lifetimes of TOE
      have been interpreted by using the rotamer model for the fluorescence decay of
      tryptophan. Membrane/water partition coefficients of TOE were measured in both
      its protonated and deprotonated forms. No appreciable difference was found in its
      partitioning behavior with ionization. Analysis of fluorescence polarization of
      TOE as a function of pH showed that there is a decrease in polarization with
      increasing pH, implying more rotational freedom on deprotonation. This is further
      supported by pH-dependent red edge excitation shift and the apparent rotational
      correlation time of membrane-bound TOE. TOE should prove useful in monitoring the
      organization and dynamics of tryptophan residues incorporated into membranes.

PMID- 9251803
TI  - Renormalization of the tension and area expansion modulus in fluid membranes.
AB  - Renormalization of the membrane tension and elastic area expansion modulus by
      thermally induced bending fluctuations is treated in terms of the formalism of
      Brochard, De Gennes, and Pfeuty (J. de Phys. (France). 37:1099-1104, 1976). The
      dependence of the renormalized tension on the bare membrane tension parallels the
      dependence on the fractional area extension of giant vesicles found
      experimentally by Evans and Rawicz (Physiol. Rev. Lett. 64:2094-2097, 1990), and
      suggests conditions for molecular dynamics simulations with membrane patches of
      limited size that might best represent the properties of macroscopic vesicles.

PMID- 9251802
TI  - Water permeability of polyunsaturated lipid membranes measured by 17O NMR.
AB  - Diffusion-controlled water permeation across bilayers of polyunsaturated
      phospholipids was measured by 17O nuclear magnetic resonance. In 100-nm extruded
      liposomes containing 50 mM MnCl2, water exchange between internal and external
      solutions was monitored via changes in the linewidth of the 17O water resonance
      of external water. Liposome size and shape were characterized by light scattering
      methods and determination of liposome trapped volume. At 25 degrees C, the
      following water permeability coefficients were determined: 18:0-18:1n-9 PC, 155
      +/- 24 microns/s; 18:0-18:3n-3 PC, 330 +/- 88 microns/s; and 18:0-22:6n-3 PC, 412
      +/- 91 microns/s. The addition of 1 M ethanol reduced permeability coefficients
      to 66 +/- 15 microns/s for 18:0-18:1n-9 PC and to 239 +/- 67 microns/s for 18:0
      22:6n-3 PC. Furthermore, the addition of 50 mol% 18:1n-9-18:1n-9 PE reduced the
      water permeability from 122 +/- 21 microns/s for pure 18:1n-9-18:1n-9 PC to 74 +/
      15 microns/s for the mixture. The significant increase in water permeation for
      membranes with polyunsaturated hydrocarbon chains correlates with looser packing
      of polyunsaturated lipids at the lipid-water interface and the suggested deeper
      penetration of water into these bilayers. Ethanol may block water diffusion
      pathways by occupying points of water entry into bilayers at the interface. The
      addition of dioleoylphosphatidylethanolamine increases lipid packing density and,
      consequently, reduces permeation rates.

PMID- 9251804
TI  - Membrane packing geometry of diphytanoylphosphatidylcholine is highly sensitive
      to hydration: phospholipid polymorphism induced by molecular rearrangement in the
      headgroup region.
AB  - Diphytanoylphosphatidylcholine (DPhPC) has often been used in the study of
      protein-lipid interaction and membrane channel activity, because of the general
      belief that it has high bilayer stability, low ion leakage, and fatty acyl
      packing comparable to that of phospholipid bilayers in the liquid-crystalline
      state. In this solid-state 31P and 2H NMR study, we find that the membrane
      packing geometry and headgroup orientation of DPhPC are highly sensitive to the
      temperature studied and its water content. The phosphocholine headgroup of DPhPC
      starts to change its orientation at a water content as high as approximately 16
      water molecules per lipid, as evidenced by hydration-dependent 2H NMR study at
      room temperature. In addition, a temperature-induced structural transition in the
      headgroup orientation is detected in the temperature range of approximately 20-60
      degrees C for lipids with approximately 8-11 water molecules per DPhPC.
      Dehydration of the lipid by one more water molecule leads to a nonlamellar,
      presumably cubic, phase formation. The lipid packing becomes a hexagonal phase at
      approximately 6 water molecules per lipid. A phase diagram of DPhPC in the
      temperature range of -40 degrees C to 80 degrees C is thus constructed on the
      basis of NMR results. The newly observed hydration-dependent DPhPC lipid
      polymorphism emphasizes the importance of molecular packing in the headgroup
      region in modulating membrane structure and protein-induced pore formation of the
      DPhPC bilayer.

PMID- 9251805
TI  - Force generation and phosphate release steps in skinned rabbit soleus slow-twitch
      muscle fibers.
AB  - The force-generation and phosphate-release steps of the cross-bridge cycle in
      rabbit soleus slow-twitch muscle fibers (STF) were investigated using sinusoidal
      analysis, and the results were compared with those of rabbit psoas fast-twitch
      fibers (FTF). Single fiber preparations were activated at pCa 4.40 and ionic
      strength 180 mM at 20 degrees C. The effects of inorganic phosphate (Pi)
      concentrations on three exponential processes, B, C, and D, were studied. Results
      are consistent with the following cross-bridge scheme: [formula: see text] where
      A is actin, M is myosin, D is MgADP, and P is inorganic phosphate. The values
      determined are k4 = 5.7 +/- 0.5 s-1 (rate constant of isomerization step, N = 9,
      mean +/- SE), k-4 = 4.5 +/- 0.5 s-1 (rate constant of reverse isomerization), K4
      = 1.37 +/- 0.13 (equilibrium constant of the isomerization), and K5 = 0.18 +/-
      0.01 mM-1 (Pi association constant). The isomerization step (k4) in soleus STF is
      20 times slower, and its reversal (k-4) is 20 times slower than psoas fibers.
      Consequently, the equilibrium constant of the isomerization step (K4) is the same
      in these two types of fibers. The Pi association constant (K5) is slightly higher
      in STF than in FTF, indicating that Pi binds to cross-bridges slightly more
      tightly in STF than FTF. By correlating the cross-bridge distribution with
      isometric tension, it was confirmed that force is generated during the
      isomerization (step 4) of the AMDP state and before Pi release in soleus STF.

PMID- 9251806
TI  - Interhead distances in myosin attached to F-actin estimated by fluorescence
      energy transfer spectroscopy.
AB  - Fluorescence resonance energy transfer (FRET) spectroscopy has been used to
      determine distances between probes attached to the most reactive sulfhydryl (SH1)
      group on individual myosin "heads." We measured intramolecular and intermolecular
      interhead distances as well as the distance between one head of heavy meromyosin
      (HMM) mixed with subfragment-1 (S1) heads attached to F-actin under rigor
      conditions. The SH1 cysteine was specifically labeled with either a donor (5
      ((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid) or an acceptor
      probe (5-iodoacetamidofluorescein). In free solution, the distance between these
      probes was too large to allow significant FRET, but in the rigor complex with F
      actin, intermolecular interhead distances between S1 molecules, HMM molecules, or
      S1 and HMM were determined to be 6.0-6.3 nm. The radial coordinate of the labels
      relative to F-actin was 5.0-6.4 nm. However, the intramolecular interhead
      distance in HMMs in which the two heads were labeled with D and A probes was
      estimated to be larger. The binding affinity of the second head of HMM(D/A) to F
      actin may be reduced because of heterogeneous modification of the SH1 groups,
      such that the probability of single-head binding is increased.

PMID- 9251808
TI  - Indo-1 fluorescence signals elicited by membrane depolarization in enzymatically
      isolated mouse skeletal muscle fibers.
AB  - Indo-1 fluorescence signals were measured from one extremity of enzymatically
      isolated skeletal muscle fibers of mice. An original and simple method was
      developed to allow the measurements to be made under voltage-clamp control: the
      major part of a single fiber was embedded in silicone grease, so that only a
      short portion of one end of the fiber, from which the fluorescence measurements
      were taken, was in contact with the external solution. Membrane potential was
      held and varied by using a patch-clamp amplifier in whole-cell configuration with
      a single microelectrode, the tip of which was inserted across the silicone grease
      within the insulated portion of the fiber. In response to 100-ms depolarizing
      command pulses to voltages more positive than -40 mV (from a holding potential of
      -80 mV), clear changes in fluorescence were qualitatively observed to feature a
      time course of rise and decay expected from a change in intracellular calcium
      concentration ([Ca2+]i) due to voltage-dependent sarcoplasmic reticulum (SR)
      calcium release. Although the peak [Ca2+]i elicited by a 100-ms depolarization at
      0 or +10 mV varied from fiber to fiber, it could clearly reach a value high
      enough to saturate Indo-1. The overall results show that this method represents
      an efficient way of measuring depolarization-induced [Ca2+]i changes in
      enzymatically dissociated skeletal muscle fibers.

PMID- 9251807
TI  - Actin-titin interaction in cardiac myofibrils: probing a physiological role.
AB  - The high stiffness of relaxed cardiac myofibrils is explainable mainly by the
      expression of a short-length titin (connectin), the giant elastic protein of the
      vertebrate myofibrillar cytoskeleton. However, additional molecular features
      could account for this high stiffness, such as interaction between titin and
      actin, which has previously been reported in vitro. To probe this finding for a
      possible physiological significance, isolated myofibrils from rat heart were
      subjected to selective removal of actin filaments by a calcium-independent
      gelsolin fragment, and the "passive" stiffness of the specimens was recorded.
      Upon actin extraction, stiffness decreased by nearly 60%, and to a similar degree
      after high-salt extraction of thick filaments. Thus actin-titin association
      indeed contributes to the stiffness of resting cardiac muscle. To identify
      possible sites of association, we employed a combination of different techniques.
      Immunofluorescence microscopy revealed that actin extraction increased the
      extensibility of the previously stiff Z-disc-flanking titin region. Actin-titin
      interaction within this region was confirmed in in vitro cosedimentation assays,
      in which multimodule recombinant titin fragments were tested for their ability to
      interact with F-actin. By contrast, such assays showed no actin-titin-binding
      propensity for sarcomeric regions outside the Z-disc comb. Accordingly, the
      results of mechanical measurements demonstrated that competition with native
      titin by recombinant titin fragments from Z-disc-remote, I-band or A-band regions
      did not affect passive myofibril stiffness. These results indicate that it is
      actin-titin association near the Z-disc, but not along the remainder of the
      sarcomere, that helps to anchor the titin molecule at its N-terminus and maintain
      a high stiffness of the relaxed cardiac myofibril.

PMID- 9251809
TI  - Conformational changes in actin induced by its interaction with gelsolin.
AB  - Actin cleaved by the protease from Escherichia coli A2 strain between Gly42 and
      Val43 (ECP-actin) is no longer polymerizable when it contains Ca2+ as a tightly
      bound cation, but polymerizes when Mg2+ is bound. We have investigated the
      interactions of gelsolin with this actin with regard to conformational changes in
      the actin molecule induced by the binding of gelsolin. ECP-(Ca)actin interacts
      with gelsolin in a manner similar to that in which it reacts with intact actin,
      and forms a stoichiometric 2:1 complex. Despite the nonpolymerizability of ECP
      (Ca)actin, this complex can act as a nucleus for the polymerization of intact
      actin, thus indicating that upon interaction with gelsolin, ECP-(Ca)actin
      undergoes a conformational change that enables its interaction with another actin
      monomer. By gel filtration and fluorometry it was shown that the binding of at
      least one of the ECP-cleaved actins to gelsolin is considerably weaker than of
      intact actin, suggesting that conformational changes in subdomain 2 of actin
      monomer may directly or allosterically affect actin-gelsolin interactions. On the
      other hand, interaction with gelsolin changes the conformation of actin within
      the DNase I-binding loop, as indicated by inhibition of limited proteolysis of
      actin by ECP and subtilisin. Cross-linking experiments with gelsolin-nucleated
      actin filaments using N,N-phenylene-bismaleimide (which cross-links adjacent
      actin monomers between Cys374 and Lys191) reveal that gelsolin causes a
      significant increase in the yield of the 115-kDa cross-linking product,
      confirming the evidence that gelsolin stabilizes or changes the conformation of
      the C-terminal region of the actin molecule, and these changes are propagated
      from the capped end along the filament. These results allow us to conclude that
      nucleation of actin polymerization by gelsolin is promoted by conformational
      changes within subdomain 2 and at the C-terminus of the actin monomer.

PMID- 9251811
TI  - Light chain-dependent myosin structural dynamics in solution investigated by
      transient electrical birefringence.
AB  - The technique of transient electrical birefringence was used to compare some of
      the electric and structural dynamic properties of myosin subfragment 1 (S1(elc,
      rlc)), which has both the essential and regulatory light chains bound, to
      S1(elc), which has only an essential light chain. The rates of rotational
      Brownian motion indicate that S1(elc, rlc) is larger, as expected. The permanent
      electric dipole moment of S1(elc, rlc) is also larger, indicating that the
      regulatory light chain portion of S1(elc, rlc) has a dipole moment and that it is
      aligned head-to-tail with the dipole moment of the S1(elc) portion. The permanent
      electric dipoles decrease with increasing ionic strength, apparently because of
      ion binding to surface charges. Both S1(elc, rlc) and S1(elc) have intrinsic
      segmental flexibility, as detected by the ability to selectively align segments
      with a brief weak electric field. However, unlike S1(elc), which can be
      structurally distorted by the action of a brief strong electric field, S1(elc,
      rlc) is stiffer and cannot be distorted by fields as high as 7800 V/cm applied to
      its approximately 8000 D permanent electric dipole moment. The S1 . MgADP . Pi
      analog S1 . MgADP . Vi is smaller than S1 . MgADP, for both S1(elc, rlc) and
      S1(elc). Interestingly, the smaller, stiffer S1(elc, rlc) . MgADP . Vi complex
      retains intrinsic segmental flexibility. These results are discussed within a
      framework of current hypotheses of force-producing mechanisms that involve S1
      segmental motion and/or the loss of cross-bridge flexibility during force
      production.

PMID- 9251810
TI  - Mechanical components of motor enzyme function.
AB  - Motor enzymes use energy from ATP dephosphorylation to generate movement by a
      mechanical cycle, moving and pushing in one direction while attached to their
      cytoskeletal substrate, and recovering by moving relative to their substrate to a
      new attachment site. Mainstream models assert that movement while attached to the
      substrate results from preexisting strain in the attached motor. The additional
      underlying ideas can be described in terms of three components for strain
      amplification: a rotating lever arm, multiple attached states, and elastic
      compliance. These components determine how energy is recovered during the
      mechanical cycle and stored in a strained motor. They may coexist in a real
      motor; the challenge is to determine the contributions of each component. Because
      these components can generate similar relationships between strain energy and
      strain, standard measurements of motor function do not discriminate easily
      between these components. However, important information could be is provided by
      observations that suggest weak coupling between chemical and mechanical cycles,
      observations of negative force and movement events in single motor experiments,
      and the discovery that two motors that move in opposite directions have very
      similar structures. In models incorporating changes in conformation between
      attached states, these observations are only explained easily if the
      conformational changes are tightly coupled to changes in the strength of motor
      substrate binding.

PMID- 9251812
TI  - Local dynamics of DNA probed with optical absorption spectroscopy of bound
      ethidium bromide.
AB  - We have studied the local dynamics of calf thymus double-helical DNA by means of
      an "optical labeling" technique. The study has been performed by measuring the
      visible absorption band of the cationic dye ethidium bromide, both free in
      solution and bound to DNA, in the temperature interval 360-30 K and in two
      different solvent conditions. The temperature dependence of the absorption line
      shape has been analyzed within the framework of the vibronic coupling theory, to
      extract information on the dynamic properties of the system; comparison of the
      thermal behavior of the absorption band of free and DNA-bound ethidium bromide
      gave information on the local dynamics of the double helix in the proximity of
      the chromophore. For the dye free in solution, large spectral heterogeneity and
      coupling to a "bath" of low-frequency (soft) modes is observed; moreover,
      anharmonic motions become evident at suitably high temperatures. The average
      frequency of the soft modes and the amplitude of anharmonic motions depend upon
      solvent composition. For the DNA-bound dye, at low temperatures, heterogeneity is
      decreased, the average frequency of the soft modes is increased, and anharmonic
      motions are hindered. However, a new dynamic regime characterized by a large
      increase in anharmonic motions is observed at temperatures higher than
      approximately 280 K. The DNA double helix therefore appears to provide, at low
      temperatures, a rather rigid environment for the bound chromophore, in which
      conformational heterogeneity is reduced and low-frequency motions (both harmonic
      vibrations and anharmonic contributions) are hindered. The system becomes
      anharmonic at approximately 180 K; however, above approximately 280 K,
      anharmonicity starts to increase much more rapidly than for the dye free in
      solution; this can be attributed to the onset of wobbling of the dye in its
      intercalation site, which is likely connected with the onset of (functionally
      relevant) DNA motions, involving local opening/unwinding of the double helix. As
      shown by parallel measurements of the melting curves, these motions precede the
      melting of the double helix and depend upon solvent composition much more than
      does the melting itself.

PMID- 9251813
TI  - Cooperative chiral order in the B-Z transition in random sequences of DNA.
AB  - We present a theory for cooperative chiral order in the transition between right
      handed B-DNA and left-handed Z-DNA. This theory, based on the random-field Ising
      model, predicts the characteristic length scale of Z-DNA segments. This length
      scale depends on whether the DNA is a homopolymer or a random sequence: it is
      approximately 4000 nucleotides in a homopolymer but only approximately 25
      nucleotides in a random sequence. These theoretical results are consistent with
      experiments on DNA homopolymers and random sequences.

PMID- 9251815
TI  - Spin-labeling studies of the conformational changes in the vicinity of D36, D38,
      T46, and E161 of bacteriorhodopsin during the photocycle.
AB  - Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin-labeled
      bacteriorhodopsin mutants is used to study structural changes during the
      photocycle. After exchange of the native amino acids D36 and D38 in the A-B loop,
      E161 in the E-F loop, and T46 in the putative proton channel by cysteines, these
      positions were modified by a methanethiosulfonate spin label. Time-resolved EPR
      spectroscopy reveals spectral changes during the photocycle for the mutants with
      spin labels attached to C36, C161, and C46. A comparison of the transient
      spectral amplitudes with simulated EPR difference spectra shows that the detected
      signals are due to changes in the spin label mobility and not to possible
      polarity changes in the vicinity of the attached spin label. The kinetic analysis
      of the EPR and the visible data with a global fitting procedure exhibits a
      structural rearrangement near position 161 in the E-F loop in the M state. The
      environmental changes at positions 36 and 46, however, occur during the M-to-N
      transition. All structural changes reverse with the recovery of the BR ground
      state. No structural changes are detected with a spin label attached to C38.

PMID- 9251814
TI  - Coupling of cytochrome and quinone turnovers in the photocycle of reaction
      centers from the photosynthetic bacterium Rhodobacter sphaeroides.
AB  - A minimal kinetic model of the photocycle, including both quinone (Q-6) reduction
      at the secondary quinone-binding site and (mammalian) cytochrome c oxidation at
      the cytochrome docking site of isolated reaction centers from photosynthetic
      purple bacteria Rhodobacter sphaeroides, was elaborated and tested by cytochrome
      photooxidation under strong continuous illumination. The typical rate of
      photochemical excitation by a laser diode at 810 nm was 2.200 s-1, and the rates
      of stationary turnover of the reaction center (one-half of that of cytochrome
      photooxidation) were 600 +/- 70 s-1 at pH 6 and 400 +/- 50 s-1 at pH 8. The rate
      of turnover showed strong pH dependence, indicating the contribution of different
      rate-limiting processes. The kinetic limitation of the photocycle was attributed
      to the turnover of the cytochrome c binding site (pH < 6), light intensity and
      quinone/quinol exchange (6 < pH < 8), and proton-coupled second electron transfer
      in the quinone acceptor complex (pH > 8). The analysis of the double-reciprocal
      plot of the rate of turnover versus light intensity has proved useful in
      determining the light-independent (maximum) turnover rate of the reaction center
      (445 +/- 50 s-1 at pH 7.8).

PMID- 9251816
TI  - Magneto-aerotaxis in marine coccoid bacteria.
AB  - Magnetotactic cocci swim persistently along local magnetic field lines in a
      preferred direction that corresponds to downward migration along geomagnetic
      field lines. Recently, high cell concentrations of magnetotactic cocci have been
      found in the water columns of chemically stratified, marine and brackish
      habitats, and not always in the sediments, as would be expected for persistent,
      downward-migrating bacteria. Here we report that cells of a pure culture of a
      marine magnetotactic coccus, designated strain MC-1, formed microaerophilic bands
      in capillary tubes and used aerotaxis to migrate to a preferred oxygen
      concentration in an oxygen gradient. Cells were able to swim in either direction
      along the local magnetic field and used magnetotaxis in conjunction with
      aerotaxis, i.e., magnetically assisted aerotaxis, or magneto-aerotaxis, to more
      efficiently migrate to and maintain position at their preferred oxygen
      concentration. Cells of strain MC-1 had a novel, aerotactic sensory mechanism
      that appeared to function as a two-way switch, rather than the temporal sensory
      mechanism used by other bacteria, including Magnetospirillum megnetotacticum, in
      aerotaxis. The cells also exhibited a response to short-wavelength light (< or =
      500 nm), which caused them to swim persistently parallel to the magnetic field
      during illumination.

PMID- 9251817
TI  - Localization and orientation of functional water molecules in bacteriorhodopsin
      as revealed by polarized Fourier transform infrared spectroscopy.
AB  - Linear dichroic difference Fourier transform infrared spectra upon formation of
      the M photointermediate were recorded with oriented purple membranes. The purpose
      was to determine the angle of the directions of the dipole moments of 1) the
      water molecule whose O-H stretching vibration appears at 3643 cm-1 for the
      unphotolyzed state and 3671 cm-1 for the M intermediate, and 2) the C=O bond of
      protonated Asp85 in the M intermediate. The angle of 36 degrees we find for the
      C=O of the protonated Asp85 in the M intermediate is not markedly different from
      26 degrees for unprotonated Asp85 in the model based on cryoelectron diffraction,
      indicating the absence of gross orientation changes in Asp85 upon its
      protonation. The O-H band at 3671 cm-1 of a water molecule in the M intermediate,
      although its position has not determined, is fixed almost parallel to the
      membrane plane. For the unphotolyzed state the angle of the water O-H to the
      membrane normal was determined to be 60 degrees. On the basis of these data and
      the structural model, we place the water molecule in the unphotolyzed state at a
      position where it forms hydrogen bonds with the Schiff base, Asp85, Asp212, and
      Trp86.

PMID- 9251818
TI  - The essential dynamics of Cu, Zn superoxide dismutase: suggestion of intersubunit
      communication.
AB  - A 300-ps molecular dynamics simulation of the whole Cu, Zn superoxide dismutase
      dimer has been carried out in water, and the trajectory has been analyzed by the
      essential dynamics method. The results indicate that the motion is defined by few
      preferred directions identified by the first four to six eigenvectors and that
      the motion of the two monomers at each instant is not symmetrical. The vectors
      symmetrical to the eigenvectors are significantly sampled, suggesting that, on
      average, the motions of the two subunits will exchange. Large intra- and
      intersubunit motions involving different subdomains of the protein are observed.
      A mechanical coupling between the two subunits is also suggested, because
      displacements of the loops surrounding the active site in one monomer are
      correlated with the motion of parts of the second toward the intersubunit
      interface.

PMID- 9251819
TI  - A myoglobin mutant designed to mimic the oxygen-avid Ascaris suum hemoglobin:
      elucidation of the distal hydrogen bonding network by solution NMR.
AB  - The solution 1H NMR structure of the active site and ligand dissociation rate for
      the cyanomet complex have been determined for a sperm whale myoglobin triple
      mutant Leu29(B10)-->Tyr, His64(E7)-->Gln, Thr67(E10)-->Arg that mimics the distal
      residue configuration of the oxygen-avid hemoglobin from Ascaris suum. A double
      mutant that retains Leu29(B10) was similarly investigated. Two-dimensional NMR
      analysis of the iron-induced dipolar shifts, together with the conserved proximal
      side structure for the two mutants, allowed the determination of the orientations
      of the paramagnetic susceptibility tensor for each complex. The resulting
      magnetic axes, together with paramagnetic relaxation and steady-state NOEs, led
      to a quantitative description of the distal residue orientations. The distal
      Tyr29(B10) in the triple mutant provides a strong hydrogen bond to the bound
      cyanide comparable to that provided by His64(E7) in wild-type myoglobin. The
      distal Gln64(E7) in the triple mutant is sufficiently close to the bound cyanide
      to severe as a hydrogen bond donor, but the angle is not consistent with a strong
      hydrogen bond. Dipolar contacts between the Arg67(E10) guanidinium group and the
      Gln64(E7) side chain in both mutants support a hydrogen-bond to the Gln64(E7)
      carbonyl group. The much lower oxygen affinity of this triple mutant relative to
      that of Ascaris hemoglobin is concluded to arise from side-chain orientations
      that do not allow hydrogen bonds between the Gln64(E7) side-chain NHs and both
      the ligand and Tyr29(B10) hydroxyl oxygen. Cyanide dissociation rates for the
      reduced cyanide complexes are virtually unaffected by the mutations and are
      consistent with a model of the rate-determining step as the intrinsically slow Fe
      C bond breaking that is largely independent of any hydrogen bonds to the cyanide
      nitrogen.

PMID- 9251820
TI  - Thermal unfolding in a GCN4-like leucine zipper: 13C alpha NMR chemical shifts
      and local unfolding curves.
AB  - 13C alpha chemical shifts and site-specific unfolding curves are reported for 12
      sites on a 33-residue, GCN4-like leucine zipper peptide (GCN4-lzK), ranging over
      most of the chain and sampling most heptad positions. Data were derived from NMR
      spectra of nine synthetic, isosequential peptides bearing 99% 13C alpha at sites
      selected to avoid spectral overlap in each peptide. At each site, separate
      resonances appear for unfolded and folded forms, and most sites show resonances
      for two folded forms near room temperature. The observed chemical shifts suggest
      that 1) urea-unfolded GCN4-lzK chains are randomly coiled; 2) thermally unfolded
      chains include significant transient structure, except at the ends; 3) the coiled
      coli structure in the folded chains is atypical near the C-terminus; 4) only
      those interior sites surrounded by canonical interchain salt bridges fail to show
      two folded forms. Local unfolding curves, obtained from integrated resonance
      intensities, show that 1) sites differ in structure content and in melting
      temperature, so the equilibrium population must comprise more than two molecular
      conformations; 2) there is significant end-fraying, even at the lowest
      temperatures, but thermal unfolding is not a progressive unwinding from the ends;
      3) residues 9-16 are in the lowest melting region; 4) heptad position does not
      dictate stability; 5) significant unfolding occurs below room temperature, so the
      shallow, linear decline in backbone CD seen there has conformational
      significance. It seems that only a relatively complex array of conformational
      states could underlie these findings.

PMID- 9251822
TI  - Formation of stable polypeptide monolayers at interfaces: controlling molecular
      conformation and orientation.
AB  - The molecular self-organization and structural properties of peptide assemblies
      at different interfaces, using either amphipathic or hydrophobic polypeptide
      helices, is described. The two peptides under investigation form stable
      monolayers on the water surface under the conservation of their molecular
      conformation, as studied by circular dichroism and polarization-modulation
      Fourier transform infrared (FTIR) spectroscopy. Using surface plasmon resonance
      and reflection-absorption FTIR, we show that such molecular layers can be
      transferred unaltered to solid substrates. Most importantly, the molecular
      orientation of the hydrophobic helices on solid supports such as gold can be
      controlled by choosing a particular procedure for the layer formation. The
      helices were oriented parallel to the interface in Langmuir-Blodgett monolayers,
      and perpendicular to the interface in self-assembled monolayers. Our reflection
      absorption FTIR measurements have delivered for the first time direct
      experimental evidence for the molecular conformation and orientation of pure
      peptide monolayers. Suitable reference spectra of polypeptides with defined
      conformation and orientation are necessary to use this technique for the
      determination of the molecular orientation of peptides in monomolecular films. We
      have solved the problem for alpha-helical polypeptides by using bacteriorhodopsin
      as a reference in combination with synthetic alpha-helices of defined interfacial
      orientation. The present study shows the possibility of constructing immobilized
      peptide monolayers with predefined macroscopic properties and molecular structure
      by choosing the proper polypeptide amino acid sequence, the technique used for
      layer formation, and the supporting surface properties.

PMID- 9251821
TI  - Time-resolved fluorescence study of the single tryptophans of engineered skeletal
      muscle troponin C.
AB  - The regulatory domain of troponin C (TnC) from chicken skeletal muscle was
      studied using genetically generated mutants which contained a single tryptophan
      at positions 22, 52, and 90. The quantum yields of Trp-22 are 0.33 and 0.25 in
      the presence of Mg2+ (2-Mg state) and Ca2+ (4-Ca state), respectively. The large
      quantum yield of the 2-Mg state is due to a relatively small nonradiative decay
      rate and consistent with the emission peak at 331 nm. The intensity decay of this
      state is monoexponential with a single lifetime of 5.65 ns, independent of
      wavelength. In the 4-Ca state, the decay is biexponential with the mean of the
      two lifetimes increasing from 4.54 to 4.92 ns across the emission band. The decay
      associated spectrum of the short lifetime is red-shifted by 19 nm relative to the
      steady-state spectrum. The decay of Trp-52 is biexponential in the 2-Mg state and
      triexponential in the 4-Ca state. The decay of Trp-90 requires three exponential
      terms for a satisfactory fit, but can be fitted with two exponential terms in the
      4-Ca state. The lower quantum yields (< 0.15) of these two tryptophans are due to
      a combination of smaller radiative and larger nonradiative decay rates. The
      results from Trp-22 suggest a homogeneous ground-state indole ring in the absence
      of bound Ca2+ at the regulatory sites and a ground-state heterogeneity induced by
      activator Ca2+. The Ca(2+)-induced environmental changes of Trp-52 and Trp-90
      deviate from those predicted by a modeled structure of the 4-Ca state. The
      anisotropy decays of all three tryptophans show two rotational correlation times.
      The long correlation times (phi 1 = 8.1-8.3 ns) derived from Trp-22 and Trp-90
      suggest an asymmetric hydrodynamic shape. TnC becomes more asymmetric upon
      binding activator Ca2+ (phi 1 = 10.1-11.6 ns). The values of phi 1 obtained from
      Trp-52 are 3-4 ns shorter than those from Trp-22 and Trp-90, and these reduced
      correlation times may be related to the mobility of the residue and/or local
      segmental flexibility.

PMID- 9251824
TI  - Helicobacter pylori survival in gastric mucosa by generation of a pH gradient.
AB  - Helicobacter pylori has been established as the major causative agent of human
      active gastritis and is an essential factor in peptic ulcer disease and gastric
      cancer. The mechanism that has been proposed for H. pylori to control its
      inhospitable microenvironment happens to coincide with the pH control technique
      developed by us. This technique was developed to separate an acidic environment
      from a basic environment for a sequential enzymatic reaction by the hydrolysis of
      urea within a thin layer of immobilized urease. In this paper, a mathematical
      model is presented to consider how H. pylori survives the gastric acidity. The
      computed results explain well the experimental data available involving H.
      pylori.

PMID- 9251823
TI  - Single-molecule microscopy on model membranes reveals anomalous diffusion.
AB  - The lateral mobility of lipids in phospholipid membranes has attracted numerous
      experimental and theoretical studies, inspired by the model of Singer and
      Nicholson (1972. Science, 175:720-731) and the theoretical description by Saffman
      and Delbruck (1975. Proc. Natl. Acad. Sci. USA. 72:3111-3113). Fluorescence
      recovery after photobleaching (FRAP) is used as the standard experimental
      technique for the study of lateral mobility, yielding an ensemble-averaged
      diffusion constant. Single-particle tracking (SPT) and the recently developed
      single-molecule imaging techniques now give access to data on individual
      displacements of molecules, which can be used for characterization of the
      mobility in a membrane. Here we present a new type of analysis for tracking data
      by making use of the probability distribution of square displacements. The
      potential of this new type of analysis is shown for single-molecule imaging,
      which was employed to follow the motion of individual fluorescence-labeled lipids
      in two systems: a fluid-supported phospholipid membrane and a solid
      polymerstabilized phospholipid monolayer. In the fluid membrane, a high-mobility
      component characterized by a diffusion constant of 4.4 microns2/s and a low
      mobility component characterized by a diffusion constant of 0.07 micron2/s were
      identified. It is proposed that the latter characterizes the so-called immobile
      fraction often found in FRAP experiments. In the polymer-stabilized system,
      diffusion restricted to corrals of 140 nm was directly visualized. Both examples
      show the potentials of such detailed analysis in combination with single-molecule
      techniques: with minimal interference with the native structure, inhomogeneities
      of membrane mobility can be resolved with a spatial resolution of 100 nm, well
      below the diffraction limit.

PMID- 9251826
TI  - Electrorotation of single yeast cells at frequencies between 100 Hz and 1.6 GHz.
AB  - The determination of complete electrorotation spectra of living cells has been
      made possible by the development of a quadrature generator and an electrode
      assembly that span the frequency range between 100 Hz and 1.6 GHz. Multiple
      spectra of single cells of the yeast Saccharomyces cerevisiae have been measured
      at different medium conductivities ranging from 0.7 to 550 microS cm-1. A
      spherical four-shell model was applied that simulated the experimental data well
      and disclosed the four-layer structure of the cell envelope attributed to the
      plasma membrane, the periplasmic space, and a thick inner and a thin outer wall
      region. Below 10 kHz an additional rotation effect was found, which changed its
      direction depending on the ionic strength of the medium. This is supposed to be
      connected with properties of the cell surface and its close vicinity. From the
      four-shell simulation the following physical properties of cell compartments
      could be derived: specific capacitance of plasma membrane (0.76 microF cm-2),
      periplasmic space (0.5 microF cm-2), and outer wall region (0.1 microF cm-2). The
      conductivity of cytoplasm, plasma membrane, and inner wall region were found to
      vary with medium ionic strength from 9 to 12 mS cm-1, 5.8 nS cm-1 to
      approximately 50 nS cm-1, and 6 microS cm-1 to 240 microS cm-1, respectively.

PMID- 9251825
TI  - Heterogeneity of epidermal growth factor binding kinetics on individual cells.
AB  - Binding of fluorescein-conjugated epidermal growth factor (EGF) to individual
      A431 cells at 4 degrees C is measured by a quantitative fluorescence imaging
      technique. After background fluorescence and cell autofluorescence photobleaching
      corrections, the kinetic data are fit to simple models of one monovalent site and
      two independent monovalent sites, both of which include a first-order dye
      photobleaching process. Model simulations and the results from data analysis
      indicate that the one-monovalent-site model does not describe EGF binding
      kinetics at the single-cell level, whereas the two-site model is consistent with,
      but not proved by, the single-cell binding data. In addition, the kinetics of
      binding of fluorescein-EGF to different cells from the same coverslip often
      differ significantly from each other, indicating cell-to-cell variations in the
      binding properties of the EGF receptor.

PMID- 9251827
TI  - High-gain, low-noise amplification in olfactory transduction.
AB  - It is desirable that sensory systems use high-gain, low-noise amplification to
      convert weak stimuli into detectable signals. Here it is shown that a pair of
      receptor currents underlying vertebrate olfactory transduction constitutes such a
      scheme. The primary receptor current is an influx of Na+ and Ca2+ through cAMP
      gated channels in the olfactory cilia. External divalent cations improve the
      signal-to-noise properties of this current, reducing the mean current and the
      current variance. As Ca2+ enters the cilium, it gates Cl- channels, activating a
      secondary depolarizing receptor current. This current amplifies the primary
      current, but introduces little additional noise. The system of two currents plus
      divalent cations in the mucus produces a large receptor current with very low
      noise.

PMID- 9251828
TI  - Introducing dielectrophoresis as a new force field for field-flow fractionation.
AB  - We present the principle of cell characterization and separation by
      dielectrophoretic field-flow fractionation and show preliminary experimental
      results. The operational device takes the form of a thin chamber in which the
      bottom wall supports an array of microelectrodes. By applying appropriate AC
      voltage signals to these electrodes, dielectrophoretic forces are generated to
      levitate cells suspended in the chamber and to affect their equilibrium heights.
      A laminar flow profile is established in the chamber so that fluid flows faster
      with increasing distance from the chamber walls. A cell carried in the flow
      stream will attain an equilibrium height, and a corresponding velocity, based on
      the balance of dielectrophoretic, gravitational, and hydrodynamic lift forces it
      experiences. We describe a theoretical model for this system and show that the
      cell velocity is a function of the mean fluid velocity, the voltage and frequency
      of the signals applied to the electrodes, and, most significantly, the cell
      dielectric properties. The validity of the model is demonstrated with human
      leukemia (HL-60) cells subjected to a parallel electrode array, and application
      of the device to separating HL-60 cells from peripheral blood mononuclear cells
      is shown.

PMID- 9251829
TI  - Stable magnetic field gradient levitation of Xenopus laevis: toward low-gravity
      simulation.
AB  - We have levitated, for the first time, living biological specimens, embryos of
      the frog Xenopus laevis, using a large inhomogeneous magnetic field. The magnetic
      field/field gradient product required for levitation was 1430 kG2/cm, consistent
      with the embryo's susceptibility being dominated by the diamagnetism of water and
      protein. We show that unlike any other earth-based technique, magnetic field
      gradient levitation of embryos reduces the body forces and gravity-induced
      stresses on them. We discuss the use of large inhomogeneous magnetic fields as a
      probe for gravitationally sensitive phenomena in biological specimens.

PMID- 9251830
TI  - Conservative surgery for renal cell carcinoma.
AB  - Conservative surgery was initially limited to patients with localized RCC present
      bilaterally or in a solitary kidney, in whom radical nephrectomy would
      necessitate immediate renal replacement therapy. Today, the widespread use of
      abdominal ultrasound as screening modality in patients with nonspecific or
      unrelated symptoms allows the detection of renal parenchymal tumors rarely seen
      before: asymptomatic, small and unilateral neoplasms, often surrounded by a thick
      and complete pseudocapsule. Global renal function and contralateral kidney are
      usually normal and the patients show good performance status. For these reasons
      and because of the generally good results of the first experiences, several
      authors advocate conservative surgery as an elective indication. Recently, some
      studies have reported promising results with this approach. On the other hand,
      some controversial issues persist (multifocality of RCC, low risk of local
      relapse and renal failure after radical surgery, low incidence of tumor in the
      contralateral kidney) reducing the opportunity to perform nephron-sparing surgery
      when the contralateral kidney is normal. In the present study, we report our
      experience of nephron-sparing surgery for RCC and we review the current and
      international opinion concerning this treatment.

PMID- 9251831
TI  - [Is surgery useful in kidney cancer with lymph node invasion?].
AB  - SUMMARY: lymph node involvement in renal cell carcinoma is factor of very poor
      prognosis. In a series of 55 node-positive patients, 33 (60%) had simultaneous
      renal vein or vena cava invasion and 32 (58.2%) had metastases. Gross lymph node
      involvement was found in 39 patients (70.9%). Patients without venous invasion or
      metastasis may have a prolonged survival. In this group, those with microscopic
      nodal involvement can be cured, as the 10 and 15-year the actuarial survival rate
      is 54.5% Formal lymphadenectomy might have played a role in these results.
      Surgery can be performed when vein invasion is present without metastasis, but
      the prognosis is generally poor. Survival does not seem to be influenced by
      surgery when metastasis is present, regardless of the vein status.

PMID- 9251832
TI  - [Renal cancer presenting as parietal-temporal cerebral metastasis and a
      persistent fever].
AB  - SUMMARY: The authors report the clinical case of a 48-year-old man presenting
      with persistent fever, in whom a brain tumour was detected. Histological
      examination of the resection specimen revealed metastasis from a renal cell
      carcinoma. The primary tumour was discovered on the right kidney which was then
      resected. The early postoperative course was favourable, but no long-term follow
      up is available.

PMID- 9251833
TI  - Chemotherapy with FUDR in the management of metastatic renal cell carcinoma.
AB  - SUMMARY: Metastatic renal cell carcinoma has a poor prognosis, requiring systemic
      therapy, in addition to radical nephrectomy. Since August 1989, 50 patients were
      treated with continuous, systemic, chronobiological infusion of FUDR
      (floxuridine) at our Institution. We reported 11.7% of objective responses, a
      long period of stable disease and low toxicity. We also compared our actuarial
      survival with the results obtained with recombinant IL-2 treatment.

PMID- 9251834
TI  - A monoamine hypothesis for the pathophysiology of paraphilic disorders.
AB  - A monoamine pathophysiological hypothesis for paraphilias in males is based on
      the following data: (i) the monoamines norepinephrine, dopamine, and serotonin
      are involved in the appetitive dimension of male sexual behavior in laboratory
      animals; (ii) data gathered from studying the side effect profiles of
      antidepressant psychostimulant, and neuroleptic drugs in humans suggest that
      alteration of central monoamine neurotransmission can have substantial effects on
      human sexual functioning, including sexual appetite; (iii) monoamine
      neurotransmitters appear to modulate dimensions of human and animal
      psychopathology including impulsivity, anxiety, depression, compulsivity, and
      pro/antisocial behavior, dimensions disturbed in many paraphiliacs; (iv)
      pharmacological agents that ameliorate psychiatric disorders characterized by the
      aforementioned characteristics, especially central serotonin enhancing drugs, can
      ameliorate paraphilic sexual arousal and behavior.

PMID- 9251835
TI  - Psychoendocrinological assessment of the menstrual cycle: the relationship
      between hormones, sexuality, and mood.
AB  - The role of sex hormones in sexuality and mood across the menstrual cycle was
      investigated. Twenty-one normal health women were followed for one menstrual
      cycle. Blood samples were taken frequently, and analyzed for estradiol,
      progesterone, testosterone, androstenedione, dehydroepiandrosterone sulfate,
      cortisol, and sex hormone-binding globulin. A diary concerning sexual interest
      and behavior, and different moods, was completed daily. Although the sample was
      not large, a clear effect of menstrual cycle phase on levels of testosterone and
      the free testosterone index was demonstrated. In a preliminary screening
      interview, 11 of the 21 women had reported that they suffered from premenstrual
      complaints (PC), the other 10 had reported no complaints in the premenstrual
      phase (NPC). Significant differences between the two groups were established in
      estradiol and the estradiol-progesterone ratio, with the NPC group having higher
      levels of both endocrine parameters across different menstrual samples.
      Psychologically, a cycle effect on tension and sexual interest was demonstrated.
      The NPC group reported a peak in sexual interest in the premenstrual phase,
      whereas the PC group reported a peak in the ovulatory phase. There was a
      difference between the two groups in feelings of fatigue but not in other moods
      across the menstrual cycle. The study provides further evidence of the importance
      of androgen levels in women's sexuality and shows again that the relationship
      between menstrual cycle phase and sexuality is much clearer than between phase
      and mood.

PMID- 9251836
TI  - Comparing gay and bisexual men on sexual behavior, condom use, and psychosocial
      variables related to HIV/AIDS.
AB  - Interviews were conducted with 750 men, recruited from a variety of sources in
      Chicago, who reported sex with men in the past 3 years. Behavioral criteria were
      used to establish groups of gay and bisexual men. We predicted that gay men,
      compared to bisexual men, would report more male sexual partners, more experience
      with receptive sex, and more tolerant attitudes toward homosexuality. The only
      reliable difference between the gay and bisexual men with respect to number of
      partners was that gay men were more likely to have had a steady male partner or
      lover. Gay men were more likely than bisexual men to have engaged in receptive
      sex, including unprotected receptive anal sex. Bisexual men were more self
      homophobic and saw other people as less accepting of same-sex activity. There
      were no differences between gay and bisexual men in other psychosocial variables.
      Interventions designed to reduce the transmission of HIV/AIDS need to consider
      differences in gay and bisexual men's sexual behavior and attitudes toward
      homosexual behavior.

PMID- 9251837
TI  - Correlates of increased sexual satisfaction.
AB  - Comparisons of nationally representative survey data of the population ages 18-54
      years in 1971 (N = 2252) and 1992 (N = 1718) from Finland show that sexual
      satisfaction has greatly increased particularly among women. Some predictors of
      sexual satisfaction of men and women are examined on the basis of the 1992 survey
      data on people ages 18-74 years (N = 2250). Correlations between social
      background factors, sexual ideas and assertiveness, optional relationships,
      sexual practices, organism, and satisfaction with sexual intercourse were
      calculated. To control the simultaneous effect of the variables explaining
      satisfaction, path analyses were conducted. Results show that young age, a
      sexually unreserved and a nonreligious childhood home, early start of sexual
      life, high education, sexual assertiveness, considering sexuality important in
      life, reciprocal feeling of love, use of sex materials, frequent intercourse,
      many-sided (versatile) sexual techniques, and frequent orgasm correlate with
      finding sexual intercourse pleasurable. There were some gender differences in the
      connections between the independent factors and satisfaction with coitus. The
      importance of sexuality in life, love, and the use of sexual materials were
      connected directly to physical sexual satisfaction among men but only indirectly
      among women. For women, but not for men, young age and early start of sexual life
      correlated with enjoyment of intercourse. The greater sexual dissatisfaction of
      women compared to men, which still prevails, may be due to their late start of
      sexual life, conservative sexual attitudes, unimportance of sexuality in life,
      lack of sexual assertiveness, and use of restricted sexual techniques. The
      emancipation of women may change these ideas and practices of women. This might
      lessen the gender gap in physical sexual satisfaction.

PMID- 9251838
TI  - Self-reported childhood abuse among sex and violent offenders.
AB  - Few prior studies have compared the childhood abuse experiences of different
      types of offenders. In this pilot study, the childhood abuse experiences of sex
      offenders (n = 16) and violent offenders (n = 16) were examined with
      retrospective structured interviews. The sex offenders reported significantly
      more psychological abuse, especially verbal abuse, and also tended to have
      experienced slightly more physical and sexual abuse than the violent offenders.
      In general, the sex offenders remembered their parents in a more negative light
      than the comparison group. The offender groups did not differ from each other in
      the total amount of self-reported early conduct disorder symptoms. The sex
      offenders appeared to come from more abusive childhood family environments, but
      the conclusions remain tentative due to the small sample and retrospective data
      collection.

PMID- 9251839
TI  - Sexual orientation and professional dance.
AB  - The stereotypical professional male dancer is a gay man. However, little if any
      systematic research has investigated the validity of this stereotype, much less
      the reasons why male sexual orientation would be associated with interest in
      dance. We interviewed 136 professional dancers about the prevalence of
      homosexuality among dancers, the dancers' own sexual development, and
      relationships between dancers of different sexual orientations. Dancers estimated
      that over half of male dancers are gay, but that only a small minority of female
      dancers are lesbian. Gay men recalled more intense early interest in dance
      compared to heterosexual men and women, and were more feminine as boys than were
      heterosexual men. Gay men's homosexual feelings typically preceded their dance
      experience, and only one gay man felt that his dance experiences may have
      influenced his sexual orientation. Heterosexual men voiced some mild complaints
      about gay male dancers, but these were balanced by positive sentiments.

PMID- 9251840
TI  - Homosexuality and dance: relations to AIDS and Hawai'i.

PMID- 9251841
TI  - Increased rate of apoptosis and decreased expression of bcl-2 protein in
      peripheral blood lymphocytes from patients with active systemic lupus
      erythematosus.
AB  - Defective regulation of apoptosis may play a role in the development of
      autoimmune diseases, and the proto-oncogene bcl-2 is known to inhibit cells from
      undergoing apoptosis. We studied the rate of apoptosis with the expression of bcl
      2 in peripheral blood lymphocytes of patients with systemic lupus erythematosus
      (SLE). A lower proportion of lymphocytes were bcl-2+ in SLE patients with active
      disease (median 84.9%) than in patients with inactive disease or normal (medians
      95.3% and 97.1% respectively, p < 0.05). The rate of apoptosis of freshly
      isolated PBL was significantly higher in SLE patients than in normal (medians
      1.2% vs 0.5%, p < 0.05). After 48-hour culture the apoptotic rate was further
      increased in SLE patients, particularly those with active disease (SLE overall
      34.2%, active 62% inactive 27.5%, normal 11.25%). These findings support the
      theory that in SLE patients increased apoptosis may provide a source of
      extracellular nuclear antigens which stimulate the autoimmune response and form
      immune complexes with autoantibodies.

PMID- 9251842
TI  - The role of the methacholine inhalation challenge in adult patients presenting
      with chronic cough.
AB  - One hundred and twenty two patients who were presenting with chronic persistent
      cough for more than 3-4 weeks were studied. Using anatomical and stepwise
      approach, we could identify the cause of chronic cough in 96% of the patients.
      The most common causes were due to postnasal drip syndrome (PND) (45%) and
      bronchial asthma (26%). We also demonstrated the important role of methacholine
      inhalation challenge in the diagnostic work up. The procedure could identify the
      patients who had bronchial hyperresponsiveness (BHR) in 52% of the cases. The
      severity degree of the BHR was classified into three levels. Mild or nonspecific
      BHR was defined as PC20 16-25 mg/ml. This could be found in many diseases such as
      PND and bronchiectasis. Moderate degree of BHR (PC20 8-16 mg/ml) was found in
      patients with PND and asthma. PC20 of less than 8 mg/ml was considered to be the
      most severe degree and it seemed to be specific for the diagnosis of asthma
      (positive predictive value 100%). Other condition that caused chronic cough were
      drug-induced, especially angiotensin-converting enzyme inhibitors,
      gastroesophageal reflux disease (GERD), idiopathic pulmonary fibrosis, subgottic
      cancer and idiopathic cough. These conditions may require invasive diagnostic
      work up, such as fiberoptic bronchoscopy and tissue biopsy. The treatment of
      chronic cough was according to the etiology. Thus, the patients presenting with
      chronic cough should be investigated to identify the cause, and it was not just
      only the administration of cough suppressant drugs in these patients.

PMID- 9251843
TI  - Lymph node pathology in patients with a clinical diagnosis of angioimmunoblastic
      lymphadenopathy with dysproteinemia (AILD): an analysis of 37 cases.
AB  - Lymph node pathology was analyzed in 37 patients clinically diagnosed as having
      angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). Results confirmed
      AILD in 11 cases and were compatible with AILD in 2 cases. Reactive lymphoid
      hyperplasia was found in 15 cases, 2 cases had angiofollicular lymphoid
      hyperplasia or Castleman's disease, atypical lymphoid hyperplasia suggestive of
      malignant lymphoma was observed in 3 cases, and malignant lymphoma was diagnosed
      in the remaining 4 cases. The histopathologic features of AILD which differed
      from reactive lymphoid hyperplasia were effacement of lymph node architecture,
      vascular arborization, high endothelial venules, and capsular infiltration (p
      value < 0.05). Lymphodepletion and PAS-positive interstitial material were
      occasionally found in both groups (p-value > 0.05). Among the 15 cases with
      pathology of reactive lymphoid hyperplasia, we identified 8 cases with
      hyperplastic lymphoid follicles, interfollicular plasmacytosis and
      hypervascularity which we designated as a hyperimmune reaction. This study
      emphasizes the necessity of lymph node examination in all patients with a
      clinical suspicion of AILD.

PMID- 9251844
TI  - HLA class I typing by one-dimensional isoelectric focusing and identification of
      the new variants in Thai population.
AB  - One-dimensional isoelectric focusing (1D-IEF) is the technique to define HLA
      class I antigens based on difference in isoelectric point of HLA molecules.
      Different IEF subtypes are shown in different populations. In this study, 1D-IEF
      was employed to study HLA-A and -B subtypes in Thai population. A panel of 117
      samples including all serologically defined HLA-A and -B antigens in Thai
      population were typed by 1D-IEF. Serological specificities and subtypes
      correlated well with IEF results and some antigens with unclear serological
      specificities could be confirmed by IEF. In addition, more subtypes could be
      obtained by IEF than by serology. A total of 17 IEF subtypes from HLA-A and 31
      IEF subtypes from HLA-B could be identified. The subtypes predominantly found in
      Thai population were A2.3, A24.2, A11.1, A33.2, B15.2, B7.1 and B13.1. In
      addition, new IEF variants were identified in HLA-B35, B5, B56 and B48. The band
      positions of these variants were different from those previously described. These
      IEF subtypes are HLA gene products which may be important in transplantation. The
      combination of IEF and serology for HLA typing can provide a better definition of
      each allelic product of HLA-A and -B.

PMID- 9251845
TI  - The latency rate of human herpesvirus 6 (HHV6) in positive and negative human
      immunodeficiency virus (HIV) infection of intravenous drug users (IVDU).
AB  - The seropositive and latency rates of HHV6 among IVDU with positive and negative
      HIV and control group were demonstrated. By immunofluorescent antibody test, no
      differences in the seropositive rates were found among these three groups. All
      groups had seropositive rate at the average 89% and GMT antibody 1:26. This meant
      that most of them had previous infection with HHV6. In addition, HHV6-DNA was
      determined and classified into subgroups: HHV6A and HHV6B, by polymerase chain
      reaction. The prevalence of HHV6-DNA indicated HHV6 latency in vivo. High latency
      rate of HHV6 was found in all three groups (the average 54%). Moreover, HHV6B
      (49%) had a higher frequency than HHV6A (5%); HHV6a was found only in IVDU with
      or without HIV infection. The result suggested that the HHV6 latency in IVDU with
      positive HIV may possibly transactivate HIV. The pathogenesis of HHV6 in AIDS
      patients should be further investigated. However, this research finding is useful
      for treatment, health care, prevention and control of AIDS in case of dual
      infections and latency of herpesvirus infection in AIDS.

PMID- 9251846
TI  - Indirect immunoperoxidase staining of Crithidia luciliae for detecting anti
      dsDNA: comparison with other serodiagnostic tests.
AB  - The indirect immunoperoxidase (IIP) method was modified and improved for
      detecting anti-dsDNA. Using fetal calf serum to block the non-specific antibodies
      and staining with chromatic substrate solution at pH 6.2, the performance time is
      substantially decreased and the patterns of positive and negative staining are
      easily distinguished. IIP was compared with indirect hemagglutination (IHA),
      latex agglutination (LA) and the standard method indirect immunofluorescent
      technique (IFT). The sensitivities and specificities of the three methods were
      studied in 507 sera from various sources. Using IFT as the gold standard,
      sensitivities of IIP, IHA, LA were 98.18%, 88.18% and 50.91% respectively, and
      the corresponding specificities were 99.5%, 98.24% and 100%. There was a good
      correlation between titers of IFT and IIP (Spearman correlation coefficient =
      0.77, p < 0.001) with no significant difference between the titer of both tests
      (Wilcoxon Matched-Pairs Signed-Rank test, p = 0.143). These results indicate that
      the modified IIP method is both highly sensitive and specific and only needs a
      light microscope to perform it.

PMID- 9251847
TI  - International clinical trials of HIV vaccines: I. Phase I trial of an HIV-1
      synthetic peptide vaccine in Bangkok, Thailand.
AB  - A randomized, double blind, placebo controlled Phase I trial of a prototype human
      immunodeficiency virus type 1 (HIV-1) synthetic peptide vaccine was conducted in
      Bangkok, Thailand, to evaluate the safety and immunogenicity of the vaccine in a
      population of healthy adults at low risk for HIV infection, and to establish
      essential infrastructure for future HIV vaccine trials in Thailand. Thirty
      volunteers (25 males; 5 females) were recruited and randomized into 3 groups,
      receiving 3 intramuscular injections of either 100 micrograms vaccine (N = 12) or
      500 micrograms vaccine (N = 12) or alum placebo (N = 6) on weeks 0, 4 and 25. The
      vaccine was well tolerated without any serious adverse effects. HIV-1 specific
      ELISA responses were detected in 20/24 subjects who received the vaccine, with V3
      binding antibody titers ranging from 1:69 to 1:5,041. HIV-1 (MN) specific
      neutralizing antibody was detected in 19/20 of subjects with detectable HIV-1
      specific binding antibody. Neutralization titers ranged from 1:14 to 1:1,294,
      which were less than titers observed in HIV-infected subjects. The results of
      this study indicate that the vaccine was well tolerated, and that the vaccine
      stimulated anti-HIV humoral immune responses in Thai subjects. The successful
      undertaking of this first HIV vaccine trial conducted in Thailand provided
      important preparatory information surrounding volunteer recruitment and
      motivations, and paves the way for future trials of HIV vaccines in Thailand.

PMID- 9251848
TI  - Specific monoclonal antibodies to Fasciola gigantica.
AB  - Monoclonal antibodies (mAbs) were produced against soluble metabolic products
      (excretory/secretory; ES) of the liver fluke, Fasciola gigantica. The ES antigen
      was obtained from spent culture medium in which the adult flukes had been
      maintained in vitro. From two cell fusions, the mAbs produces were exclusively
      associated with either IgG or IgM isotypes. When screened against a panel of
      homologous and heterologous parasite antigens by indirect ELISA, two mAbs were
      highly specific for F. gigantica. The remainder cross-reacted extensively with
      other parasites. Results from immunoblotting and immunofluorescence exhibited two
      patterns of reactivity. The first group of mAbs which recognized the multiple
      bands between > 14.4-27.5 kDa gave extremely bright fluorescence over all major
      muscular systems, vitelline gland, testes and intestinal caeca. The second group
      which reacted with the 185 kDa band showed a bright fluorescence over a thinner
      muscular layer underlying the tegument, intestinal caeca and testes.

PMID- 9251849
TI  - Triggers of hair cell regeneration in the avian inner ear.
AB  - We performed an in vitro study in order to determine possible triggers of hair
      cell regeneration in the chick basilar papilla following degeneration. We
      compared the response of sensory epithelium damaged by collagenase treatment with
      that damaged by acoustic trauma. The former exhibited no proliferative activity,
      but the latter did. The basilar papillae damaged by acoustic trauma could have
      proliferating activity in medium containing fetal bovine serum (FBS) or epidermal
      growth factor (EGF) but not in the medium without FBS or EGF. These findings
      indicate that regeneration of basilar papillae depends on the manner of cell
      death and that FBS or EGF is required for regeneration.

PMID- 9251850
TI  - Emerging auditory response interactions to harmonic complexes in field L of the
      zebra finch.
AB  - Auditory responses of single units to harmonic complexes were studied in field L
      of the adult male zebra finch (Poephila guttata) to understand the origin of song
      selectivity in HVc. One of the attributes in this song selectivity is a large
      increase in response interactions when tones are presented simultaneously. Single
      units in the subdivisions of field L-L1, L2 and L3, were examined to see where
      these response interactions to harmonic complexes begin to develop along the
      auditory pathway towards HVc. Results showed relatively simple stereotyped
      response in L2 and widely varying ones in L1 and L3. The responses of some
      neurons in L1 and L3 to signals composed of the simultaneous sum of two harmonic
      complexes significantly differed from the linear sum of their responses to
      individual harmonic complexes whereas the neurons of L2 showed relatively weak
      response interactions. These neurons in L1 and L3 exhibited strong response
      interactions to harmonic complexes comparable to those of song-selective neurons
      in HVc. Thus, L1 and L3 are suggested to have emerging selective response
      properties and to provide auditory inputs relevant to the song selective HVc
      neurons.

PMID- 9251851
TI  - Experimental otitis media induced by nonviable Moraxella catarrhalis in the
      guinea pig model.
AB  - Moraxella catarrhalis is a normal resident of the human nasopharyngeal flora, but
      it is also isolated from middle ear fluid of acute otitis media and otitis media
      with effusion patients. To determine whether M. catarrhalis has direct
      pathogenicity in the middle ear, heat-killed M. catarrhalis was inoculated into
      the middle ear bullae of guinea pigs, and the inflammatory response was
      investigated. Middle ear mucosal histopathology observed in M. catarrhalis
      inoculated ears included subepithelial edema, capillary dilatation, thickening of
      lamina propria mucosa, inflammatory cell and erythrocyte infiltration into the
      lamina propria mucosa. Inflammatory cell numbers, lysozyme and myeloperoxidase
      concentrations in the middle ear washing suspensions of M. catarrhalis-inoculated
      ears were significantly higher than control ears throughout the experiment.
      Therefore, nonviable M. catarrhalis induced middle ear inflammation and
      mucoperiosteal histopathology, which might be caused by direct injury of the
      nonviable bacteria (e.g. lipooligosaccharide or outer membrane proteins) and
      metabolic products of inflammatory cells.

PMID- 9251852
TI  - Transtympanic gentamicin in the treatment of Meniere's disease.
AB  - Aminoglycosides enable a pharmacological approach, before resorting to surgery,
      to the treatment of Meniere's disease (MD) proving unamenable to routine medical
      treatment. The staging of MD is an essential preliminary step in the
      implementation of a specific and personalized treatment with transtympanic
      gentamicin. The ideal condition is the presence of endolymphatic hydrops with
      little or no damage to the cochlear and vestibular hair cells. The technical
      aspects of the method are discussed. In 21 patients with unilateral Meniere's
      disease in various stages, this treatment achieved the regression of vertigo in
      86% of cases; hearing was better in 19% of cases, preserved in 62% and worse in
      19%; tinnitus regressed totally or partially in 62% of cases; aural fullness also
      regressed totally or partially in 57% of cases.

PMID- 9251853
TI  - The role of immune complex in otitis media with effusion.
AB  - Fifteen chinchillas were inoculated with immune complexes of Streptococcus
      pneumoniae into the tympanic cavity, and with formalin-killed bacteria into the
      opposite side. Middle ear effusion (MEE) were found in 14 ears having inoculation
      with immune complexes and in only four ears having inoculation with formalin
      killed S. pneumoniae. In another experiment, 20 chinchillas received intra
      tympanic inoculation with live S. pneumoniae after systemic immunization with
      formalin-killed S. pneumoniae of the same strain. As a control, 12 chinchillas
      were inoculated with live bacteria of the same strain into the tympanic cavity
      without pre-immunization. MEE was observed in nine of pre-immunized animals and
      persistent MEE lasting for more than 3 weeks was observed in seven of the
      animals. In control, persistent MEE was not observed. Though six animals
      developed otitis media with effusion (OME). The results suggest that the
      formation of immune complexes in the tympanic cavity plays an important role in
      the occurrence of persistent MEE after pneumococcal otitis media.

PMID- 9251854
TI  - Prussak's space: chronological development and routes of aeration.
AB  - Investigation of Prussak's space and its relationship to adjacent spaces is
      important in elucidating the cause of retraction pocket and cholesteatoma
      formation in this space. This study was designed to quantitatively characterize
      the chronological development of Prussak's space and its relationship to adjacent
      spaces in temporal bones. One-hundred and forty-nine human temporal bone slides
      (115 normal, 28 with otitis media with effusion, three with retraction pockets
      and three with attic type cholesteatoma) including specimens ranging from fetal
      to adult bones were studied. Prussak's space was formed and sufficient aeration
      routes established by 4 years of age in normal temporal bones. In temporal bones
      with otitis media with effusion, however, the growth of Prussak's space was
      suppressed and few routes for aeration established until 10 years of age. In
      normal temporal bones, Prussak's space developed with aeration routes sufficient
      to avert the negative pressure which can result in retraction pocket formation in
      the pars flaccida of the tympanic membrane.

PMID- 9251855
TI  - Risk factors for sudden deafness: a case-control study.
AB  - In order to investigate risk factors for idiopathic sudden sensorineural hearing
      loss (sudden deafness), a case-control study was done in 109 patients with sudden
      deafness who visited our hospital between 1992 and 1994, with 109 controls
      matched to each patient by gender and age. Odds ratio (OR) and 95% confidence
      interval (CI) for smoking habits, drinking habits, dietary habits, environmental
      noise, past history of disease, sleeping hours, appetite, fatigue, incidence of
      common cold were obtained. Fatigue (OR: 3.28; 95% CI: 1.36-7.90) and loss of
      appetite (OR: 8:00; 95% CI: 1.00-64.0) elevated the risk for sudden deafness.
      Those who ate many fresh vegetables were at a decreased risk (OR: 0.48; 95% CI:
      0.24-0.96 for light-colored vegetables, OR: 0.55; 95% CI: 0.30-1.02 for green
      yellow vegetables). Personal histories of hypertension and thyroid disease, and
      susceptibility to colds appeared to be positively associated with the risk (0.05
      < P < 0.10). Smoking habits, drinking habits and environmental noise had no
      significant association with sudden deafness. These results suggested that
      environmental factors, including diet, may be importantly involved in the genesis
      of sudden deafness.

PMID- 9251856
TI  - Distribution of choline acetyltransferase (ChAT) immunoreactive nerve fibers in
      the nasal mucosa; especially in the respiratory epithelium.
AB  - The distribution and morphological construction of cholinergic nerve fibers in
      the respiratory nasal mucosa of the rat and human were investigated using choline
      acetyltransferase (ChAT) activities by means of light microscopy, confocal laser
      scanning microscopy and electron microscopy. It was observed that ChAT
      immunoreactive (IR) nerve fibers were distributed to form fine varicosities
      around the blood vessels and seromucous glands under the epithelium and at the
      basement membrane and within the epithelium. Electron microscopy showed that the
      ChAT-IR nerve fibers within the epithelium terminated as free nerve endings. Some
      of them were in close contact with goblet cells. The distribution of ChAT
      immunoreactive fibers resembled that of vasoactive intestinal polypeptide-IR
      nerve fibers.

PMID- 9251857
TI  - Preferential infiltration by activated eosinophils in allergic sinusitis.
AB  - Although Type I allergy is a trigger for provoking chronic inflammation, whether
      allergic sinusitis (AS) can be distinguished from sinusitis due to chronic
      infection is still debated. This study was performed to characterize inflammatory
      cells in AS and to determine whether patients with AS differ from patients with
      chronic suppurative sinusitis (CSS). 5 patients with AS and 10 patients with CSS
      were investigated. Cellular infiltration was studied using immunohistochemistry
      with monoclonal antibodies using CD3, CD4, CD8, CD25, major basic protein
      (BMK13), eosinophil cationic protein (EG2), neutrophil elastase, and tryptase.
      There were no differences in CD3+, CD4+, CD25+, and tryptase+ cells between the
      groups. Whereas the total number of eosinophils (BMK13+) also did not
      significantly differ, the number of activated eosinophils (EG2+) was
      significantly higher (P < 0.05) in patients with AS. Furthermore, a statistically
      significant increase in the percentage of activated eosinophils to total
      eosinophils (P < 0.05) was observed in patients with AS. In contrast, the number
      of neutrophil elastase+ cells was significantly higher (P < 0.05) in patients
      with CSS. These results suggest that patients with AS can be distinguished
      immunohistochemically from patients with CSS, with AS being distinguished by
      activated eosinophil infiltration.

PMID- 9251858
TI  - Quantification of X-ray opacity of the maxillary sinus in the Waters' view.
AB  - Plain X-ray filming such as that in the Waters' view is a simple and inexpensive
      method used in daily practice to briefly evaluate the severity of inflammation of
      the paranasal sinuses. The maxillary sinus is the largest and simplest in shape
      among all sinuses and is usually clearly observed on a film in the Waters' view.
      We attempted to obtain a quantitative index of the X-ray opacity of the maxillary
      sinus using X-ray films in the Waters' view. A copper wedge was placed to the
      left side of the subject's face and was filmed simultaneously. The X-ray film was
      digitized with an image digitizer. The X-ray density of each pixel was then
      converted to an absolute value for the copper thickness with a medical image
      processor. The mean pixel value in the region of interest at the maxillary sinus
      (M(R)) and that at the ipsilateral orbit (O) were determined. The difference,
      M(R) - O, was found to have a significant correlation with the average visual
      grading of the severity of inflammation of the maxillary sinus by 10
      otolaryngologists. Thus M(R) - O Can serve as an objective measure of the X-ray
      opacity of the maxillary sinus. The use of this index during the follow-up period
      is advisable, especially in children, because of greatly reduced amount of X-ray
      exposure compared with that in computed tomography.

PMID- 9251859
TI  - Body growth in relation to tonsillar enlargement.
AB  - Severe airway obstruction caused by tonsillar enlargement can result in
      disturbances in body growth. In this study, 1136 children between 7 and 12 years
      of age, were evaluated and the size of their tonsils was investigated with regard
      to height and weight. This study was performed in the course of school screening,
      and correlation between estimated tonsil size and height and weight of the
      children was sought. Statistically, no such correlation was found (P > 0.05).

PMID- 9251861
TI  - Epithelial hyperplasia of the larynx a clinical follow-up study.
AB  - In this retrospective study, the records of 40 patients with epithelial
      hyperplasia of the larynx, seen between 1980-1991, were reviewed to determine the
      incidence of malignant transformation during long term follow-up. The mean follow
      up time was 58.6 months. The initial pathological diagnoses were hyperkeratosis
      in one case, parakeratosis in one, dyskeratosis in 12 and dysplasia in 26. During
      follow up, nine patients developed carcinoma in situ and/or invasive carcinoma.
      Of these, two patients had been diagnosed with dyskeratosis without dysplastic
      cells at the initial biopsy. It is therefore important to follow up patients with
      epithelial hyperplasia of the larynx even when no dysplastic cells are found at
      the time of diagnosis.

PMID- 9251860
TI  - A case of pleomorphic adenoma of the epiglottis. Bilateral vocal-cord paralysis
      after YAG laser surgery.
AB  - Pleomorphic adenoma of the larynx is a rare disorder, and until recently has been
      treated mainly by approaches involving pharyngotomy. We encountered a case of
      pleomorphic adenoma originating from the laryngeal surface of the epiglottis and
      removed it using a YAG laser through a suspension laryngoscope. This case was
      complicated by delayed-onset bilateral vocal-cord paralysis, the causes of which
      are also discussed.

PMID- 9251862
TI  - Sclerosing inflammatory pseudotumor arising from the carotid artery region.
AB  - We report a 42-year-old female patient with sclerosing inflammatory pseudotumor.
      She had found a mass in her left neck after she caught a cold. An elastic hard
      mass (25 x 15 mm), unaccompanied by any other symptoms, was palpated adjacent to
      the left carotid bifurcation. The mass extended vertically along the common
      carotid artery, partially adhering to the pulsating artery. Under
      ultrasonography, the mass was characterized by a homogenized low echoic shadow
      surrounding the left common carotid artery. Angiography revealed a slight
      narrowing of the common carotid artery with a surrounding hypovascular mass.
      Computerized tomography (CT) and magnetic resonance imaging (MRI) both showed a
      mass enclosing the carotid artery; a Ga scintigram also showed a highly
      concentrated mass. Surgical removal of the mass included removing part of the
      carotid artery, internal and external carotid arteries and sympathetic trunk. The
      left internal jugular vein was transplanted to connect the common carotid artery
      to the internal carotid artery. Although the hypoglossal and vagus nerves adhered
      to the mass, they were preserved by sharp dissection with the scalpel. Although
      hypoglossal and vagus nerve dysfunction were observed temporarily after the
      surgery, Horner's syndrome appeared and persisted. Histological examination
      revealed markedly fibrotic tissues surrounding the carotid artery with extensive
      lymphocyte and plasmacyte infiltration and a diagnosis of sclerosing inflammatory
      pseudotumor was made.

PMID- 9251863
TI  - Primary ectopic meningioma in the right ethmoid sinus: a case report.
AB  - A 29-year-old female with primary ectopic meningioma in the right ethmoid sinus
      was reported. She was treated by a right lateral rhinotomy with total removal of
      the tumor and the subsequent clinical course was good. Contrast enhanced magnetic
      resonance image (MRI) was most informative to define the tumor and decide the
      surgical procedure, in which it was demonstrated as well circumscribed mass
      lesion with considerable homogeneous contrast enhancement.

PMID- 9251864
TI  - Subjective experience in brain-injured patients and their close relatives: a
      European Brain Injury Questionnaire study.
AB  - Results are reported from an international project the aim of which has been to
      develop and validate a wide-ranging questionnaire suitable for administration to
      brain-injured patients and their relatives. A self-report questionnaire
      concerning subjective experience of cognitive, emotional and social difficulties
      (The European Brain Injury Questionnaire, EBIQ) was administered to a group of
      905 brain-injured patients, and close relatives to these competed a parallel
      version of the questionnaire concerning the brain-injured person. The sample was
      drawn from seven European countries together with Brazil. The same questionnaire
      was also administered to a group of 203-non-brain-injured controls, similarly in
      self-report and relative-report versions. Scales relating to eight specific areas
      of functioning, together with a global scale, are derived from the questionnaire
      and their internal reliability was estimated in the present data. Analyses of the
      63 items of the questionnaire showed consistently greater levels of problems for
      the brain-injured group, especially as indicated by relatives. This pattern was
      substantially replicated among the nine scales. The scales discriminated well
      between stroke patients and those who had suffered a traumatic brain injury.
      There was also a tendency for reported problems to be greater for patients who
      were surveyed later post-injury (> or = 19 months) rather than earlier.
      Comparison of sets of controls derived from two countries (France and Brazil)
      showed small but important differences. It is concluded that the questionnaire
      has an acceptable reliability and validity, but that it will be necessary to
      obtain culturally relevant non-brain-injured control data when employing it in
      different countries.

PMID- 9251865
TI  - Neuropsychological sequelae of head injury in a New Zealand adolescent sample.
AB  - The purpose of this study was to determine the nature and extent of any
      difficulties experienced by students after head injury, and the degree to which
      these were recognized by their parents and teachers. All year 10 students at a co
      educational high school in New Zealand were surveyed for information regarding
      incidence, aetiology and severity of head injury-related symptomatology and
      general everyday competency. A proportion of students reporting injury (mostly
      mild) and a matched control group were studied in more detail. Information was
      obtained through a self-report questionnaire, neuropsychological measures, and
      teacher and parent rating forms. Apart from trials 5 and 6 of the AVLT, in which
      the head-injury group scored significantly lower than the control group, there
      were no other significant differences between the two groups on
      neuropsychological measures. There was a low level of agreement between students,
      teachers and parents with regard to behavioural and cognitive difficulties that
      the students were experiencing.

PMID- 9251866
TI  - Corpus striatum and traumatic brain injury.
AB  - The possibility of a 'subcortical' syndrome differentially affecting memory in
      traumatic brain injury (TBI) subjects was examined. Magnetic resonance imaging
      scans of 46 traumatic brain injured male patients were compared with those of 34
      male control subjects. Surface area measurements of the corpus striatum were
      calculated for both groups. Results demonstrated no significant differences in
      corpus striatum surface area measurements. Additionally, TBI patients were
      grouped according to severity of injury, as well as degree of corpus striatum
      atrophy, and neuropsychological outcome was examined. There were modest (r =
      0.35) but significant correlations between corpus striatum degeneration and the
      delayed recall trial and total score of the Rey Auditory Verbal Learning Test,
      but no other correlations between neuropsychological and corpus striatal surface
      area were significant. Because subcortical pathology may have a differential
      effect on memory, recognition and recall memory were further analysed, but no
      significant differences were found. TBI subjects with the smallest corpus
      striatum values did not test significantly different from TBI patients with
      normal corpus striatum values or differences in cortical atrophy, as determined
      by a ventricle-to-brain ratio. These findings suggest that there is not a unique
      pattern of subcortical pathology involving the corpus striatum in TBI.

PMID- 9251867
TI  - The relationship between sexual abuse and mild traumatic brain injury.
AB  - It remains unclear why some individuals with mild traumatic brain injury (MTBI)
      complain of cognitive deficits many months after the injury. Given
      neuropathological changes associated with prolonged stress, such as occurs with
      repeated sexual abuse (SA), it seems possible that individuals who experienced SA
      might be predisposed to greater deficits after MTBI. Four groups of subjects were
      administered measures of cognitive and emotional functioning. These groups were
      those with MTBI (n = 10), those with a history of SA (n = 10), those with both
      MTBI and SA (n = 10), and normal control (NC) subjects (n = 10). Compared to the
      NC subjects, those with MTBI demonstrated deficits in working memory, those with
      SA demonstrated deficits in executive functioning, and those with both MTBI and
      SA demonstrated the greatest number of deficits which were in working memory,
      executive functioning and memory. Tests of anxiety, depression and post-traumatic
      stress disorder, while demonstrating significant symptoms in all clinical groups,
      did not correlate with the neuropsychological tests that differentiated the
      groups.

PMID- 9251868
TI  - Prolonged, severe behavioural disturbance following traumatic brain injury: what
      can be done?
AB  - At the end of 1994 the New South Wales Department of Health identified the need
      for a specialized unit for people with a brain injury who exhibited aggressive
      and violent behaviour at such a level that they could not be cared for in
      standard rehabilitation programmes and who were not mentally ill as defined by
      the Mental Health Act. An interim unit based on the principles of
      neurobehavioural rehabilitation was opened in the grounds of Lidcombe Hospital,
      and in January 1995 the first patient (SA) was admitted. Following intervention
      weekly aggression decreased from a peak of 159 incidents to zero after ten
      months. Other maladaptive behaviours also decreased markedly. Simultaneous
      attempts to improve adaptive behaviours were successful. At 11 months follow-up
      in the community, these gains were all noted to have been maintained. This
      article discusses the need for specialized units dealing with severe behavioural
      problems following head injury, presents the case of SA for illustrative
      purposes, and addresses some of the more common criticisms of such environments.

PMID- 9251869
TI  - Responsiveness of non-IHS migraine and tension-type headache to sumatriptan.

PMID- 9251870
TI  - A clinical review of the adaptive role of vasopressin in migraine.
AB  - Vasopressin is a naturally available neuropeptide that subserves important
      vasomotor, antinociceptive, behavior control, fluid and electrolyte balance,
      platelet aggregation and blood coagulation functions. This review focuses on the
      clinical phenomena of migraine that are likely to influence vasopressin
      bioavailability or efficacy as well as the modulating influence of vasopressin
      itself. As part of a complex homeostatic adjustment to stress and pain, the
      intricacies of vasopressin metabolism may have particular relevance to the
      pathophysiology of migraine.

PMID- 9251871
TI  - Regional cerebral blood flow and oxygen metabolism during migraine with and
      without aura.
AB  - Eleven cases of migraine with and without aura were investigated with positron
      emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism
      (rCMRO2) and oxygen extraction (rOER) were measured during baseline (n = 11),
      aura (n = 6), headache (n = 10) and after treatment with sumatriptan (n = 4).
      Data were analysed using an ROI-based approach from 26 different anatomically
      defined regions, and also an exploratory approach whereby all subjects were
      normalized to a stereotactic brain atlas; t-maps were constructed by depicting
      significant changes between states. The exploratory approach revealed a region
      corresponding to the primary visual cortex with significant reductions in rCBF
      (23.1%) and rCMRO2 (22.5%), but no change in rOER during the headache phase
      compared to baseline. These data suggest that cerebral ischemia was not the
      primary cause of the attacks in these cases.

PMID- 9251872
TI  - Oxidative stress and platelet responsiveness in migraine.
AB  - The aim of this study is to investigate whether oxidative stress may represent a
      pivotal determinant of the altered functional features of platelets in
      migraineurs during the headache-free period. Twenty-three patients with migraine
      with aura, free of attack, and 23 healthy volunteers were enrolled for the study.
      The involvement of an oxidative condition appears confirmed by the statistically
      significant increase (p < 0.001) of plasma levels of thiobarbituric acid-reactive
      substances which may be considered a marker for oxidative stress and themselves
      strong-pro-oxidants. Such oxidative status seems to induce in platelets of
      migraineurs increased membrane rigidity (p < 0.001), reduced cytosolic calcium in
      the resting condition and after thrombin stimulation (p < 0.001), and decreased
      aggregatory responses to ADP and collagen. These findings indicate that the "in
      vitro" anomalous platelet behavior in migraineurs, observed in headache-free
      periods, may be considered as the transient expression of the exhausted platelets
      to "in vivo" stimulation and probably related to an increased vulnerability to
      oxidative stress.

PMID- 9251873
TI  - Migraine with and without aura in the same patient: expression of a single
      clinical entity?
AB  - Migraine with aura and migraine without aura may be different clinical
      expressions of one disease. This theory is debated, however. In order to further
      address the issue, we administered a standardized questionnaire to 45
      migraineurs. The results indicate a significant overlap between migraine with and
      without aura, most importantly with respect to response to therapy; 70% of
      patients had similar responses.

PMID- 9251874
TI  - Responsiveness of non-IHS migraine and tension-type headache to sumatriptan.
AB  - In a long-term efficacy and safety study, 424 patients were treated with
      sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed
      with migraine based on IHS criteria but individual migraine attacks treated in
      the study were physician diagnosed; not necessarily required to meet IHS
      criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg
      sc) indicated that 43 patients had treated at least one migraine that fulfilled
      IHS criteria for tension-type headache. Analysis of this population revealed they
      treated 232 headaches. Of these headaches, 114 were classified per IHS criteria
      as migraine; 76 as tension-type; and 42 as non-IHS migraine (not classifiable as
      IHS migraine or IHS tension-type headache). Of the 114 migraines, a positive
      response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73
      responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to
      sumatriptan. An equivalent response to sumatriptan among three diagnostic groups
      of headache supports the concept of a common biologic mechanism involving 5HT1
      receptors that spans a range of clinical presentations.

PMID- 9251875
TI  - Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open
      randomized cross-over study.
AB  - In an open, randomized cross-over study in 124 patients, we compared the
      efficacy, safety and patient preference of oral and subcutaneous sumatriptan in
      the acute treatment of migraine. Patients were treated for 3 attacks or 3 months
      and then crossed over. Primary clinical efficacy was defined as a reduction in
      headache severity on a four-point self-rating scale from severe (3) or moderate
      (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h
      after the administration of subcutaneous and 4 h after the administration of oral
      sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral
      sumatriptan in relieving headache (over all three attacks 78% vs 61%
      improvement), improving clinical disability (55% vs 41% improvement) and
      relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia
      (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h)
      than after oral sumatriptan (18 h); the number of patients experiencing a
      recurrence was similar. Patients reported more adverse events after subcutaneous
      sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all
      adverse events were mild to moderate in intensity and of short duration. Patient
      opinion was more often positive after subcutaneous sumatriptan. These results may
      be useful in counselling patients to choose between the available marketed
      formulations of sumatriptan.

PMID- 9251876
TI  - Prophylactic treatment of migraine with bisoprolol: a placebo-controlled study.
AB  - The objective of the present study was to assess the efficacy of bisoprolol in
      migraine prophylaxis. A double-blind placebo-controlled study was conducted in
      226 patients with migraine with or without aura, a migraine history of at least 2
      years at least 3 documented attacks during the 28 days run-in period. The
      duration of treatment was 12 weeks following an initial 28 days' run-in period.
      Patients reported the number of attacks and their severity in a diary. Treatment
      with bisoprolol 5 mg resulted in a significant reduction in the frequency of
      migraine attacks (39% vs 22%) compared to placebo treatment (p < 0.05). Treatment
      had no effect on the duration and severity of the attacks. Bisoprolol was well
      tolerated.

PMID- 9251878
TI  - The factor V Leiden mutation (R506Q) is not a major risk factor for migrainous
      cerebral infarction.
AB  - The etiology of migrainous cerebral infarction is unknown, but may involve
      prothrombotic coagulation abnormalities. Therefore, we studied resistance to
      activated protein C and the presence of the Arg506Gln factor V Leiden mutation in
      20 patients with migrainous cerebral infarction. Only one heterozygous carrier of
      the mutation was found, whereas other patients did not carry the mutation. This
      indicates that the factor V Leiden mutation is not a major risk factor for
      migrainous cerebral infarction.

PMID- 9251877
TI  - Double-blind randomized placebo-controlled study of homoeopathic prophylaxis of
      migraine.
AB  - Homoeopathic remedies for migraine are widely available over the counter,
      statutorily offered by the national health service in the UK, and apparently
      popular with patients. Do they work? Sixty-three outpatients with migraine with
      or without aura by IHS criteria entered a 4-month randomized placebo-controlled,
      double-blind parallel-groups trial of individualized homoeopathic prophylaxis,
      the first month being baseline with all patients on placebo. Three patients
      (4.8%) dropped out, leaving 30 in each treatment group. There were chance
      differences in attack frequency and severity between the groups at baseline
      (attacks were more frequent but less severe in the placebo group). Both groups
      improved on therapy, but neither to a great extent on the primary outcome measure
      of attack frequency (verum: -19%; placebo: -16%). Reduction was mostly in mild
      attacks on placebo, more in moderate and severe attacks on homoeopathy. Few
      adverse events were reported. Overall, there was no significant benefit over
      placebo of homoeopathic treatment. The course of change differed between groups,
      and suggested that improvement reversed in the last month of treatment on
      placebo. On this evidence we cannot recommend homoeopathy for migraine
      prophylaxis, but cannot conclude that it is without effect.

PMID- 9251879
TI  - A CPH-like picture in two patients with an orbitocavernous sinus syndrome.
AB  - Two patients with retroorbital pain syndromes with or without paresis of cranial
      nerves developed weeks after ipsilateral headache resembling chronic paroxysmal
      hemicrania (CPH) but without autonomic features. These findings might support the
      hypothesis that CPH may be caused by a pathological process in the region of the
      cavernous sinus, as has been proposed for the Tolosa-Hunt syndrome (THS).

PMID- 9251880
TI  - Are we making progress in antifungal therapy?
AB  - Contrary to the case with bacterial infections, progress in the diagnosis and
      treatment of invasive mycoses in cancer patients has been unsatisfactory.
      Amphotericin B deoxycholate has remained the drug of choice for severe invasive
      fungal infections for nearly 40 years. However, its infusion-related side
      effects, as well as its toxicity, may at times lead to dose reduction or early
      discontinuation of the treatment. The introduction of the new triazoles,
      fluconazole and itraconazole, has improved the therapeutic chances against
      several fungal infections; however, the need for a broad-spectrum drug in empiric
      antifungal therapy, the emergence of fluconazole-resistant Candida species, and
      the limitations of itraconazole in terms of speed action and erratic oral
      absorption represent important limitations. Recently, laboratory and clinical
      research has been directed at the development of new formulations of older
      classes of antifungals, the introduction of new classes of antifungals, and the
      use of immunomodulation associated with antifungal therapy. This paper reviews
      the more recent advances in the treatment of fungal infections in cancer
      patients.

PMID- 9251882
TI  - Complementary medicine.
AB  - Complementary medicine can be described as additional approaches to care outside
      of mainstream medical practice but frequently based on traditional practices of
      nonwestern cultures. These include acupuncture, meditation, massage, diet
      manipulation, and many others. Recent reviews demonstrate wide and frequent use
      of these measures, often without concurrent discussion with the patient's
      physician. One estimate is that more than $13 billion is spent annually on
      complementary techniques in the United States alone. Many patients with cancer
      turn to these techniques. Care givers need to recognize this trend, learn about
      complementary medicine, and guide patients in their proper application when
      appropriate.

PMID- 9251881
TI  - Antiemetics revisited.
AB  - In the past few years a combination of a 5-HT3 receptor antagonist plus
      dexamethasone has been shown to be the most efficacious antiemetic prophylaxis of
      acute emesis induced by cisplatin and moderately emetogenic chemotherapy. In the
      prevention of cisplatin-induced delayed emesis oral metoclopramide or
      ondansetron, both combined with dexamethasone, offer similar antiemetic
      protection. Due to its lower cost the metoclopramide regimen remains the
      treatment of choice, whereas the ondansetron one is a valid alternative treatment
      that may be preferred in patients who present acute emesis. In the prevention of
      delayed emesis induced by moderately emetogenic chemotherapy ondansetron and
      dexamethasone have been shown superior to placebo. On the other hand, a recent
      observational study suggested that patients presenting acute vomiting or acute
      moderate-severe nausea, having a high incidence of delayed emesis, should always
      receive antiemetic prophylaxis. Instead, patients obtaining complete protection
      from acute emesis may not require any antiemetic prophylaxis.

PMID- 9251883
TI  - The concept of rehabilitation of cancer patients.
AB  - The scope of supportive care and cancer rehabilitation is very wide and
      heterogeneous. In this review we focus on nutritional aspects, sexual and gonadal
      function, psychological rehabilitation, treatment of cancer pain, and
      rehabilitation of patients with bone metastases. The anorexia-cachexia syndrome
      is a particularly frequent manifestation of cancer that profoundly affects body
      image and significantly impairs quality of life of cancer patients. However,
      enteral feeding through nasogastric tubes, gastrostomies, or jejunostomies is an
      efficient method for providing long-term enteral nutrition at home and for
      contributing to complete rehabilitation after cancer therapy. Recent effort has
      focused on nutritional pharmacology and on the optimalization of the use of
      appetite-stimulating drugs, such as progestational agents. The psychological
      components of cancer, anticancer therapy, and quality of life have now been
      widely recognized and studied. Effective pharmacological and psychotherapeutic
      interventions help patients and their family to better adjust to the chronic
      stress of cancer, but more specific determinants of psychological morbidity
      should be developed. In particular, the safe and efficient use of the most recent
      classes of antidepressants and anxiolytics should be urgently studied. More than
      90% of cancer patients present one or more pain syndromes during their illness.
      The adequate use of drugs is the cornerstone of treatment. The development on new
      molecules and new routes of administration opens interesting perspectives for
      cancer pain control. Bone metastases are the source of considerable morbidity.
      Intravenous bisphosphonates have been successfully used for the treatment of the
      symptoms of metastatic bone disease, especially bone pain. Moreover, monthly
      pamidronate infusions in addition to chemotherapy reduce the mean skeletal
      morbidity rate by more than one third and contribute to the rehabilitation of
      cancer patients with bone metastases from breast cancer or with multiple myeloma.

PMID- 9251884
TI  - Cytogenetics and experimental models.
AB  - The use of cytogenetics has led to significant improvement in the diagnoses and
      classification of sarcomas. Many of the major sarcomas have been to have
      characteristic tumor-specific chromosomal translocations that are currently used
      in the diagnosis of these tumors. In the past year, a subset of Ewing's family of
      tumors and myxoid liposarcomas, which lack one of the characteristic
      translocations, were found to carry related translocations. New technologies such
      as a spectral karyotyping will likely increase out ability to identify additional
      tumor-specific translocations. The emergence of genetic alterations as prognostic
      factors, as illustrated by Ewing's family of tumors, osteosarcoma, and p53
      expression in soft tissue sarcomas in general, is discussed. The review concludes
      with laboratory applications derived from either tumor cytogenetic or gene
      function abnormalities that are related to tumor-specific translocations. It is
      anticipated that advances in diagnosis, prognosis, and modeling will translate
      into future therapeutic advances.

PMID- 9251885
TI  - Soft tissue sarcoma in adults.
AB  - The importance of a multidisciplinary group in the treatment of soft tissue
      sarcomas is well established. This approach has led to a major shift in treatment
      from a single-modality radical surgery to a more sophisticated approach with limb
      sparing resections integrated with external irradiation, interstitial
      irradiation, or both. The increasing knowledge of both the molecular mechanisms
      of sarcoma development and the biological characteristics (tumor cell
      proliferation, hypoxia, necrosis, angio-genesis) will enable us to predict
      prognosis on a more individual basis and thus allow for more selective treatment
      strategies. Studies relating these molecular markers and biological
      characteristics to treatment results obtained with surgery, radiotherapy, and
      chemotherapy are eagerly awaited.

PMID- 9251886
TI  - Osteosarcoma and other tumors of bone.
AB  - The report of results from a major randomized clinical trial of neoadjuvant
      chemotherapy for operable osteosarcoma and the experience of two groups with
      neoadjuvant chemotherapy for patients with malignant fibrous histiocytoma of bone
      mark the major clinical advances of the past year. Further work on prognostic
      factors, including p-glycoprotein, oncogenes, and genes related to cell cycle
      control, as well as promising novel therapeutics, appeared in the literature and
      will likely result in new areas of clinical investigation.

PMID- 9251887
TI  - Liver-directed therapies for gastrointestinal malignancies.
AB  - Although surgery remains the treatment of choice for hepatic malignancy, both
      primary and secondary, the majority of patients presenting with hepatic tumors
      are unfortunately not candidates for resection. A number of alternative hepatic
      directed therapies are assessed for their role in the following settings: as
      primary treatment modalities; as treatment adjuvants to surgical resection,
      including neoadjuvant therapy to downstage tumors prior to planned resection; and
      as a means of palliation when tumors are incurable. Non-surgical hepatic-directed
      therapies demonstrated to prolong survival include adjuvant portal vein
      chemotherapy infusion at the time of resection of primary colorectal cancer, and
      hepatic artery infusion in the setting of established hepatic metastases. Several
      other therapies are described but remain incompletely evaluated, including
      transplantation, microwave coagulation, injection of radiolabeled particles,
      chemoembolization, percutaneous ethanol injection, and cryosurgery. Due to the
      rarity of these tumors, many studies present results of heterogeneous populations
      of patients, making meaningful comparison difficult. Finally, it must be said
      that screening asymptomatic patients after resection of colorectal cancer with a
      view to application of hepatic-directed therapy in the setting of colorectal
      metastases is costly.

PMID- 9251888
TI  - Biological therapies for gastrointestinal cancers.
AB  - Several new agents with promising activity in gastrointestinal malignancies have
      been identified in the past several years. Despite these advances, most advanced
      gastrointestinal malignancies cannot be cured by currently available agents or
      approaches. Accordingly, efforts to develop new treatment strategies continue to
      have urgent priority. Much interesting work has been done in the past year. The
      continued evaluation of these new strategies will identify those with the
      potential to have clinical effects on patients with gastrointestinal cancers.

PMID- 9251889
TI  - The prognostic importance of tumor markers in adenocarcinomas of the
      gastrointestinal tract.
AB  - Although no serological tumor marker has yet been shown to be sufficiently
      sensitive and specific to be used in screening for colorectal, gastric, or
      pancreatic cancers, elevated pre-operative levels of carcinoembryonic antigen and
      carbohydrate antigen (CA) 19-9 correlate with advances stages of disease and a
      poorer clinical outcome. Monitoring of serum carcinoembryonic antigen after
      primary resection of colorectal cancer may identify a small percentage of
      asymptomatic patients with recurrent disease who are amenable to a second
      surgical procedure with curative intent. A new class of tumor markers that
      recognize cytokeratins, which comprise the intermediate filaments of the
      cytoskeletons of epithelial cells, is being evaluated as a prognostic factor in
      colorectal and gastric cancer. Elevated mRNA expression of matrix
      metalloproteinases and their inhibitors in tumor tissue compared with normal
      intestinal mucosa predicts for a poor prognosis after primary management of
      colorectal cancer. CA 19-9, CA 72-4, and CYFRA 21-1 may convey prognostic
      information in gastric cancer. CA 19-9 appears to be the best overall tumor
      marker for pancreatic cancer, and a subsequent rise after postoperative
      normalization may precede clinical detection of recurrent disease. CAM 17.1 is a
      new marker that has similar sensitivity but better specificity than CA 19-9 in
      pancreatic cancer. The utility of serial monitoring of these tumor markers in
      patients with advanced disease is less well established but may become helpful if
      more effective systemic therapy is developed.

PMID- 9251890
TI  - L-2-chloropropionic acid-induced neurotoxicity in the rat: a valuable model for
      studying selective neuronal cell death in vivo.
AB  - 1. L-2-Chloropropionic acid (L-CPA) is neurotoxic when administered orally as a
      neutral sodium salt in high doses to rats, resulting in a selective destruction
      of cerebellar granule cells with the result that animals develop marked
      difficulties in maintaining normal locomotion. 2. Cerebellar granule cell
      destruction is accompanied by a reduction in cerebellar glutamate and aspartate
      concentrations, reductions in the density of glutamate receptors located in the
      cerebellar granule cell layer and development of cerebellar oedema. No other cell
      type in the brain, nor other organ, is affected by L-CPA. 3. The neuronal cell
      death is necrotic in type, involving the activation of N-methyl-D-aspartate
      (NMDA) type glutamate receptors and there is some evidence for a partial role of
      nitric oxide in the development of the neurotoxicity. 4. Contrary to work
      performed on NMDA mediated cell death using neuronal cell culture approaches, L
      CPA-induced granule cell death does not appear to arise from the production of
      excess quantities of cytotoxic free radicals, but may involve selective calcium
      activated proteases, such as the calpains. 5. Tentative evidence suggests that L
      CPA may interfere with voltage-dependent calcium channels in the cerebellum
      leading to activation of the cell death and resulting in the destruction of the
      granule cells. 6. In conclusion, L-CPA-induced neurotoxicity may provide valuable
      information on the neurochemical pathways involved in neuronal cell death that is
      associated with many neurological diseases.

PMID- 9251892
TI  - The mechanisms of action of disease-modifying antirheumatic drugs: a review with
      emphasis on macrophage signal transduction and the induction of proinflammatory
      cytokines.
AB  - 1. Rheumatoid arthritis (RA) is probably the most common source of treatable
      disability. A major problem in modern rheumatology is that the mechanism(s) of
      action of the currently used disease-modifying antirheumatic drugs (DMARDs)
      remain unclear. Many of these drugs entered rheumatology mainly through clinical
      intuition and have been used for decades. 2. The former T-cell-centered paradigm
      of rheumatoid inflammation has given way to a model of inflammation highlighting
      the macrophage and its proinflammatory cytokines. In particular, tumor necrosis
      factor alpha (TNF-alpha) has gained prominence as a central proinflammatory
      mediator in RA, and antibodies against TNF-alpha have been successfully used in
      patients with RA. 3. This review will summarize the recent advances in
      determining the mechanisms of action of the currently used DMARDs, with
      particular emphasis on their effects on the induction of TNF-alpha and
      interleukin 1 (IL-1) in mononuclear phagocytes. Although some DMARDs, such as
      auranofin, antimalarials and tenidap, act as inhibitors of the induction of these
      cytokines in monocytes or macrophages or both, other drugs, such as methotrexate,
      D-penicillamine and aurothiomalate, do not seem to affect either TNF-alpha or IL
      1. 4. The drugs' effects on proinflammatory cytokine induction are correlated to
      those on other macrophage responses.

PMID- 9251891
TI  - Biological effects of myricetin.
AB  - 1. Myricetin is a natural bioflavonoid whose occurrence in nature is widespread
      among plants. 2. It has been demonstrated to possess both antioxidative
      properties and prooxidative properties. 3. It is a potent anticarcinogen and
      antimutagen, although it has been shown to promote mutagenesis with the use of
      the Ames Test. 4. Its therapeutic potential and benefits in cardiovascular
      diseases and diabetes mellitus also are reviewed.

PMID- 9251893
TI  - The L-AP4 receptor.
AB  - 1. The L-2-amino-4-phosphonobutyric acid (L-AP4) receptor was originally
      discovered by the ability of L-AP4 to depress synaptic transmission in
      hippocampal glutamatergic pathways and in the retina. 2. The molecular identity
      of the L-AP4 receptor is not yet resolved; however, with the molecular cloning of
      subtypes of metabotropic glutamate receptors (mGluRs), high affinity targets for
      L-AP4 have been identified. 3. As the information on the pharmacology of the
      mGluRs and the electrophysiological and biochemical studies on L-AP4 receptor
      physiology becomes elaborated it seems evident that the L-AP4 receptor is not a
      single molecular target but may involve multiple receptor subtypes.

PMID- 9251894
TI  - Nitric oxide and septic shock.
AB  - 1. Nitric oxide (NO) is generated by three different isoforms of NO synthase, two
      of which are expressed constitutively (in endothelium: eNOS, brain: nNOS), while
      one is induced by endotoxin (LPS) or cytokines (iNOS). 2. Expression of iNOS in
      many organs or tissues in septic shock (caused by Gram-negative or Gram-positive
      bacteria) results in an enhanced formation of NO that contribute to hypotension,
      vascular hyporeactivity to vasoconstrictors, organ injury, and dysfunction as
      well as host defense. 3. Inhibition of either the expression of iNOS protein
      (e.g., with dexamethasone) or of NOS activity (e.g., with selective inhibitors of
      iNOS activity) exerts beneficial effects in animal models of shock. In contrast,
      inhibition of eNOS activity may lead to excessive vasoconstriction (adverse
      effects). 4. There is limited evidence regarding the degree of iNOS induction in
      human cells or tissues with septic shock. Preliminary data from ongoing clinical
      trials indicate that nonselective inhibitors of NOS activity (e.g., NG-methyl-L
      arginine [L-NMMA]) exert beneficial hemodynamic effects.

PMID- 9251895
TI  - The transport and binding of taxol.
AB  - 1. This review brings together the information available to date regarding how
      taxol cytotoxicity and the development of resistance to this drug is affected by
      its cellular transport and intracellular binding. 2. Taxol, a potent anticancer
      drug first extracted from the bark of the Pacific yew tree, is extremely
      effective in the treatment of a wide range of malignancies. 3. Unlike other
      antimitotic drugs, taxol promotes the formation of highly stable microtubules
      that resist depolymerization by specifically binding to the N-terminal region of
      beta-tubulin. Taxol binding alters the conformation of the tubulin subunit, thus
      greatly retarding tubulin heterodimer dissociation. 4. Cell division is then
      blocked at the mitotic stage and the cell dies. 5. Besides this central
      mechanism, taxol exerts numerous other cellular effects. 6. Observations made
      with taxol-resistant murine and human tumor cells make it increasingly clear that
      the cellular transport of taxol and its microtubule binding activity are
      important factors in the development of resistance to this drug.

PMID- 9251896
TI  - The autoradiographic perspective of central benzodiazepine receptors; a short
      review.
AB  - 1. We reviewed studies performed to characterize central benzodiazepine binding
      sites. 2. An overview of the different radioligands used to characterize BZ1 and
      BZ2 binding sites and a mapping of these central benzodiazepine sites are
      described. 3. Saturation studies carried out by autoradiogram quantification also
      are reviewed. 4. The specific use of the autoradiographic technique to carry out
      studies on ontogeny, development, and phylogeny is discussed, as well as studies
      performed using this technique on some diseases and experimental conditions, such
      as drug treatments or chemical and mechanical lesions.

PMID- 9251897
TI  - Pharmacological aspects of pentoxifylline with emphasis on its inhibitory actions
      on hepatic fibrogenesis.
AB  - 1. Pentoxifylline (PTX), a derivative of the methylxanthine theobromine, has been
      used for many years in the treatment of peripheral vascular diseases. Increased
      red blood cell flexibility, reduction of blood viscosity, and decreased potential
      of platelet aggregation are the basic actions of PTX, resulting in therapeutic
      benefits due to improved microcirculation and tissue oxygenation. 2. PTX's
      generally accepted mechanism of action is the inhibition of phosphodiesterases,
      leading to increased intracellular levels of cyclic adenosine monophosphate
      (cAMP). 3. A number of studies have shown PTX's effects on the cytokine network.
      The most relevant clinical results are the therapeutic benefits of PTX in
      attenuating the effects of tumor necrosis factor-alpha (TNF-alpha) in conditions
      such as septic shock. 4. PTX also has been found to exert antifibrogenic actions,
      using cultured fibroblasts or animal models of fibrosis, including liver
      fibrosis. 5. In hepatic stellate cell culture PTX has been shown to inhibit the
      basic reactions of liver fibrogenesis, being effective on cytokines and growth
      factors relevant in fibrogenesis of the liver, too. 6. Therefore, PTX might be an
      effective drug with few side effects in the treatment of liver fibrosis. Further
      clinical studies have to be done to establish the real therapeutic benefits of
      PTX in liver fibrosis and cirrhosis.

PMID- 9251898
TI  - Effects of sympathectomy on endothelin-1 and histamine responses of rabbit
      carotid artery.
AB  - 1. The effects of chronic sympathectomy on contractile responses of rabbit common
      carotid artery was studied in vitro. 2. Endothelin-1 (ET-1), histamine, KC1 and
      papaverine concentration-response curves of sympathectomized and sham-operated
      (control) vessels were recorded and analyzed. Effects of endothelium removal also
      were investigated. 3. The contractions elicited by ET-1 and histamine in
      sympathectomized preparations did not change when compared with controls.
      Papaverine, which produces endothelium-independent relaxation, and KC1, which
      produces endothelium-independent contraction, did not differ from controls. No
      significant difference was observed between the contractile responses of
      sympathectomized vessels and those of control vessels to ET-1 and histamine after
      the removal of endothelium. 4. These results indicate that chronic sympathectomy
      did not affect the sensitivity to exogenous ET-1 and histamine of the vascular
      smooth muscle.

PMID- 9251899
TI  - Antiarrhythmic and electrophysiological effects of the novel KATP channel opener,
      rilmakalim, in rabbit cardiac cells.
AB  - 1. The effects of rilmakalim, a potassium channel opener, were studied on rabbit
      cardiac Purkinje, ventricular muscle and atrial fibers, with the use of
      conventional microelectrode techniques. 2. Rilmakalim (0.24-7.2 microM)
      shortened, in a concentration-dependent manner, the action potential duration
      (APD) in Purkinje and ventricular muscle without affecting other parameters of
      the action potential. Pinacidil (30-300 microM) also decreased the APD of
      Purkinje fibers. 3. Rilmakalim (2.4 microM) and cromakalim (100 microM)
      hyperpolarized and abolished abnormal automaticity of cardiac Purkinje fibers
      pretreated with barium (0.2-0.3 mM). Glibenclamide (5 microM) blocked the
      hyperpolarizing effect. 4. Stable early afterdepolarizations induced in Purkinje
      fibers by berberine (100 microM) were reversibly blocked by rilmakalim (2.4
      microM), which also suppressed late afterdepolarizations induced in Purkinje
      fibers treated with ouabain (0.3-0.5 microM). 5. The rate of spontaneous
      discharges of the rabbit sinoatrial node was not affected by rilmakalim (7.2
      microM) or by pinacidil (100 microM). Both agents were also unable to affect the
      APD of atrial muscle fibers. 6. In cardiac Purkinje fibers, tetraethylammonium
      (TEA; 20 mM) significantly reduced the effects of rilmakalim (2. 4 microM) on the
      APD. However, neither TEA nor glibenclamide (100 microM) reduced the shortening
      of the APD induced by dinitrophenol (30 microM) or by salicylate (1 mM).

PMID- 9251900
TI  - Griseofulvin-induced hepatopathy due to abnormalities in heme pathway.
AB  - 1. The effect of long-term griseofulvin (GRIS) topical administration on some
      indicators of liver damage was examined. 2. Liver porphyrin accumulation was
      significant; however, no porhyrin crystals were observed under light microscopy.
      3. An earlier onset of hepatopathy was established (3-fold) increase of direct
      bilirubin values after 7 days of treatment; hepatic injury was confirmed by
      measuring a 6-fold increase of free bilirubin. 4. Enhanced values of alkaline
      phosphatase and glutamic oxalacetic transaminase (GOT) confirmed the onset of
      cholestasis. 5. Topical application of GRIS induced measurable hepatopathy.
      Nevertheless, we cannot discard the possibility that this hepatopathy could also
      be attributed in part to a direct reaction to xenobiotics.

PMID- 9251901
TI  - Histamine does not potentiate cyclic AMP-mediated amylase secretion in the guinea
      pig pancreatic acinar cells.
AB  - 1. This study investigates the interaction between histamine and the adenylate
      cyclase systems involved in the secretion of amylase in isolated guinea-pig
      pancreatic acinar cells. 2. Histamine caused does-related enhancement of amylase
      release. Similarly, incubation of acini with increasing concentrations of
      vasoactive intestinal peptide (VIP) resulted in a typical dose-dependent increase
      in amylase output. 3. When pancreatic acinar cells were incubated with histamine
      in combination with VIP, amylase secretion did not differ statistically from
      secretion induced by histamine or VIP alone and was significantly lower than
      theoretical additivity. Additionally, amylase secretion in the presence of
      histamine plus forskolin was significantly less than additive. The action of
      histamine was equally effective as VIP in causing cyclic adenosine monophosphate
      (cAMP) increase. 4. These results indicate that histamine may exert its secretory
      effects via the cyclic AMP pathway in the exocrine guinea-pig pancreas.

PMID- 9251902
TI  - Absence of histamine H3-receptors in the rabbit colon: species difference.
AB  - 1. The involvement of histamine H3-receptors in the control of colonic motility
      was investigated in the rabbit. 2. In vitro spontaneous and electrically evoked
      contractions were evaluated in preparations of proximal and distal colon, whereas
      in vivo spike activity was monitored in conscious rabbits, fitted long-term with
      bipolar electrodes along the distal colon. 3. In vitro, selective histamine H3
      receptor agonists, R(alpha)-methylhistamine and immepip (1 nM to 10 microM), and
      antagonists, thioperamide and clobenpropit (1 nM to 1 microM), did not modify
      either spontaneous motility of neurogenic contractions elicited by electrical
      field stimulation. In the same conditions, Neurogenic contractions were partially
      prevented by agonists acting at alpha2-adrenoceptors and adenosine A1- and opioid
      kappa-receptors. 4. In vivo, R(alpha)-methylhistamine, immepip (at both 100 and
      300 microgram kg-1 i.v.) and clobenpropit (1 mg kg-1 i.v.) did not significantly
      affect spontaneous spike activity in the rabbit distal colon. 5. These data
      suggest that histamine H3-receptors are not primarily involved in the control of
      colonic motility in the rabbit.

PMID- 9251903
TI  - Time course of the changes in central nitric oxide synthase activity following
      chronic treatment with morphine in the mouse: reversal by naltrexone.
AB  - 1. The time course of the effect of chronic administration of morphine on the
      activity of nitric oxide synthase (NOS) in the brain regions and spinal cord of
      the mouse was determined. The effect of naltrexone by itself on the NOS activity
      and that induced by morphine also were determined. 2. Male Swiss Webster mice
      were implanted subcutaneously with a pellet containing 25 mg of morphine free
      base for 4 days. Placebo pellet implanted mice served as controls. 3. Twenty-four
      hours after treatment with morphine, NOS activity decreased in the cerebellum,
      midbrain, cortex and remainder of the brain as well as in the spinal cord. Forty
      eight and 72 hr after the treatment with morphine, NOS activity increased in the
      cerebellum and cortex, but no change was observed in the other brain regions and
      spinal cord. Twenty-four hours after morphine pellet removal (withdrawal), NOS
      activity in all brain regions and the spinal cord has returned to normal. 4.
      Implantation of a pellet containing 10 mg of naltrexone did not alter NOS
      activity in any brain region or spinal cord for 24, 48 and 72 hr or 24 hr after
      removal of the pellet. 5. Implantation of a naltrexone pellet in conjunction with
      a morphine pellet blocked the changes in NOS activity in the brain region and
      spinal cord induced by morphine. 6. It is concluded that the initial decrease in
      NOS activity by morphine may be related to enhanced motor activity, whereas the
      increase in NOS activity in certain brain regions may be associated with
      tolerance-physical dependence development. Additionally, the changes in central
      NOS activity by morphine appear to be mediated by opioid receptors because they
      were blocked by concurrent treatment with naltrexone.

PMID- 9251904
TI  - Dopamine DA1 receptor agonist activity of YM435 in the canine renal vasculature.
AB  - 1. The renal vasodilatory effect of YM435 was used as an index of its dopamine
      DA1 receptor agonist activity and compared with that of dopamine in pentobarbital
      anesthetized dogs. 2. Intrarenal arterial administration of YM435 (0.1 to 10
      micrograms) and dopamine (1 to 100 micrograms) produced a dose-dependent increase
      in renal blood flow. The doses of YM435 and dopamine required to cause a 30
      ml/min increase in renal blood flow were 2.0 and 26.8 micrograms intra-arterially
      (IA), respectively. YM435 was therefore 13 times more potent than dopamine in
      this effect. 3. The selective dopamine DA1 receptor antagonist, SCH 23390, but
      not the selective dopamine DA2 receptor antagonist, nemonapride, caused dose
      dependent, parallel shifts to the right in the dose-responsive curve of YM435. 4.
      The present results demonstrate that YM435 is a potent and selective dopamine DA1
      receptor agonist.

PMID- 9251905
TI  - Pattern of nonadrenergic, noncholinergic responses during short- or long-lasting
      electrical stimulation in guinea-pig ileum.
AB  - 1. The pattern of responses of longitudinally oriented guinea pig ileum organ
      bath preparations was studied during short- (1-5 sec) or long-lasting (20 sec)
      electrical field stimulation (EFS, 0.8 msec, 40 V, 1-20 Hz). 2. In the presence
      of phentolamine (5 microM), propranolol (5 microM), and atropine (3 microM), the
      EFS elicited nonadrenergic, noncholinergic (NANC), tetrodotoxin (0.3 microM)
      sensitive responses. 3. The 1-sec EFS evoked relaxation. The response to 5-sec
      EFS consisted of relaxation followed by twitch, whereas relaxation, twitch and
      tonic contraction characterized the NANC response to 20-sec EFS. The maximum
      relaxation was observed at 10-Hz short- or long-lasting EFS. 4. Both N-G-nitro-L
      arginine (L-NNA, 0.1-0.5 mM) and apamin (1-5 microM) concentration dependently
      inhibited the relaxation of the NANC response to 10-Hz 20-sec EFS. During L-NNA
      treatment, the twitch and the tonic contractions were increased. The inhibitory
      effect of L-NNA was reversed by L-arginine (0.1-0.5 mM) but not by D-arginine.
      Sodium nitroprusside (1-10 microM) was without effect. 5. AP 13.2 ACOH (0.1
      microM), a blocker of Substance P receptors, inhibited the twitch and the tonic
      contractions. The contractions were decreased after desensitization of
      purinoceptors by ATP and in the presence of the GABA(A) receptor antagonist
      bicuculline (30 microM). 6. Depending on the EFS duration, a subsequent
      occurrence of relaxation and contractions characterized the NANC responses. It
      seems that relaxation is mediated by nitric oxide whereas Substance P and ATP are
      involved in the maintenance of the twitch and the tonic contractions. Nitric
      oxide appears to exert an inhibitory effect on the excitatory transmitters,
      whereas purinergic mechanism(s) could modulate the nitric oxide-dependent
      relaxation.

PMID- 9251906
TI  - 6-OHDA lesions to the central amygdala abolish angiotensins facilitation of
      object recognition in rats.
AB  - 1. We have previously reported that the dopaminergic projection from A10 ventral
      tegmental neurons and A9 neurons of substantia nigra to the central amygdala (CA)
      is, in part, responsible for the facilitatory effect of angiotensin II (AII) and
      its 3-7 fragment [AII(3-7)] on the retrieval of information in memory that is
      motivated affectively. 2. In this study, the influence of both angiotensins,
      given intracerebroventricularly at the dose of 1 nmol each in rats lesioned with
      6-OHDA to CA, on recognition memory, was tested. 3. AII and its 3-7 fragment
      significantly improved object recognition in sham-operated groups of rats.
      Bilateral 6-OHDA lesions to CA totally abolished the facilitatory effect of both
      angiotensins on object recognition. As insignificant increase of spontaneous
      locomotor activity in rats lesioned to CA did not interfere with the cognitive
      effect of AII and AII(3-7). 4. These results suggest that the dopaminergic
      projection at the CA takes part in the facilitatory effect of angiotensins on
      recognition memory.

PMID- 9251907
TI  - The NK1 antagonist GR203040 inhibits cyclophosphamide-induced damage in the rat
      and ferret bladder.
AB  - 1. The effect of the tachykinin neurokinin1 (NK1) receptor antagonist GR203040 on
      cyclophosphamide (CYP)-induced bladder damage was investigated in rats and
      ferrets. The 5-hydroxytryptamine3 receptor antagonists ondansetron and
      granisetron were similarly examined in ferrets. 2. In the rat, GR203040 (10 and
      30 mg/kg i.p.) reduced the CYP-induced plasma protein extravasation in the
      bladder by 44% and 73%, respectively (P < 0.05 and 0.005; cf. CYP controls); in
      the ferret, a 57% reduction (P < 0.005) was observed after GR203040 (0.3 mg/kg
      SC). No decrease was observed in ferrets with either ondansetron or granisetron
      (1 mg/kg SC). 3. GR203040 attenuated the CYP-induced damage in the rat and ferret
      bladder, at the same dose in the ferret previously shown to inhibit CYP-induced
      emesis.

PMID- 9251908
TI  - The antiplatelet aggregatory activity of Acacia nilotica is due to blockade of
      calcium influx through membrane calcium channels.
AB  - 1. The extract of Acacia nilotica (A. nilotica) blocked platelet aggregation
      mediated by platelet agonists, arachidonic acid (0.75 mM), ADP (4.3 microM),
      platelet activating factor (800 nM) and collagen (638 nM) in a dose-dependent
      manner. 2. The extract (0.21-1.4 mg/ml) blocked the platelet aggregation induced
      by Ca2+ ionophore, A-23187 (6 microM), in a dose-dependent manner, indicating
      that the Ca2+ influx is involved in aggregation. 3. The plant extract also
      inhibited aggregation in platelets pretreated with phorbol, 12-myristate, 13
      acetate (196 nM) alone or in combination with ADP (4.3 microM), indicating an
      effect on protein kinase C. 4. These results indicate that the antiplatelet
      aggregatory activity of the extract of A. nilotica is mainly due to blockade of
      Ca2+ channels, although evidence also suggests the involvement of protein kinase
      C.

PMID- 9251909
TI  - Thapsigargin does not affect phenylephrine-induced contractions in the
      anococcygeus muscle of rats.
AB  - 1. The aims of the present study were to investigate the contribution of
      intracellular calcium and to evaluate the effect of the antagonists of the
      intracellular calcium stores, thapsigargin and [8-(Diethylamino)-octyl-3,4,5
      trimethoxybenzoate, HC1] TMB-8, on phenylephrine-stimulated contractions of rat
      anococcygeus smooth muscle, using functional studies. 2. Phenylephrine induced
      concentration-related contractions in both 2.5 mM Ca2(+)-free EGTA media. 3. In
      Ca2(+)-free media phenylephrine stimulated successive contractions, and the
      contractile response was abolished only after approximately 26 stimulations. 4.
      In Ca2(+)-free media, after incubation with 10 microM TMB-8 for 30 min,
      phenylephrine induced concentration-response curves that shifted to the right.
      The EC50 values were not changed, and the maximum contractile response was
      reduced by 39.2 +/- 7.6% in relation to phenylephrine-stimulated responses in
      absence of TMB-8. 5. Thapsigargin (1 microM) did not alter phenylephrine
      stimulated contractions in Ca2(+)-free media. 6. These results indicate that
      intracellular Ca2+ plays an important role on phenylephrine-stimulated
      contractions on rat anococcygeus muscle and that the phenylephrine-sensitive
      intracellular Ca2+ store is not sensitive to thapsigargin.

PMID- 9251910
TI  - Effects of auro-detoxin treatment on vascular responses in mouse aorta.
AB  - 1. In this study, we investigated the effects of chronic Auro-detoxin treatment
      for 5 and 10 weeks on reactivity to vascular agonists in the mouse aorta. 2. The
      maximum contractile responses to and the -log EC50 values of phenylephrine (Phe)
      were not changed with Auro-detoxin treatment. 3. The maximum contractile
      responses to 5-hydroxytryptamine (5-HT) were not changed over 5 weeks but were
      significantly increased with Auro-detoxin treatment during a 10-week period. The 
      log EC50 values of 5-HT were found to be significantly decreased in both
      treatment groups. 4. The maximum relaxation responses to acetylcholine (ACh) were
      decreased in both treatment groups. The -log EC50 values of ACh were not changed
      in 5 weeks but significantly decreased in 10 week-treated animals. 5. Neither the
      maximum relaxation responses not the -log EC50 values of sodium nitroprusside
      (SNP) were changed with Auro-detoxin treatment. 6. These results suggest that
      chronic gold treatment affects vascular responses in the mouse aorta.

PMID- 9251912
TI  - Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic
      activity but does not produce adverse effects on female reproductive or embryonic
      development in mice.
AB  - 1. Coriolus versicolor polysaccharopeptide has been reported to exert
      immunomodulatory and antitumor actions. The present study showed that it exhibits
      analgesic activity in the hot-plate test upon intraperitoneal administration to
      ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm
      gestation in mice. It did not exert an adverse effect on mouse embryonic
      development either, as evidenced by the lack of an effect on somite number, axial
      length and the incidence of abnormalities in heartbeat, yolk sac circulation,
      optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial
      apparatus, cranial neural tube and head size. 3. Its analgesic activity would add
      to its attribute as an immunomodulatory and antitumor drug.

PMID- 9251911
TI  - Repeated administration intensifies the reinforcing effect of fencamfamine in
      rats.
AB  - 1. In the present study, we evaluated the role of repeated administration on
      conditioning place preference (CPP) induced by fencamfamine (FCF) in male rats.
      2. Repeated FCF (3.5 mg/kg) or saline once or daily for ten consecutive days
      enhanced sniffing duration and decreased locomotion and rearing duration. 3. At
      the 3.5 mg/kg dose, FCF produced a significant place-preference effect. 4.
      Repeated exposures to FCF intensified its reinforcing properties. 5. These
      results suggest that repeated FCF administration sensitizes its rewarding
      effects, as with other addictive substances.

PMID- 9251913
TI  - Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in
      isolated guinea pig papillary muscle.
AB  - 1. The cellular electrphysiological effects of EGIS-7229, a novel antiarrhythmic
      agent, were studied in guinea pig papillary muscles with the use of conventional
      microelectrode techniques. 2. The drug had a concentration-dependent biphasic
      effect on action potential duration (APD). APD was significantly lengthened at
      low concentration (3 mumol/1), whereas it was shortened at concentrations higher
      than 10 mumol/l. 3. At concentrations higher than 10 mumol/l, the drug decreased
      the maximum velocity of action potential upstroke (Vmax), the force contraction,
      and altered the restitution kinetics of APD. 4. The effect of EGIS-7229 on Vmax
      was frequently dependent; it was most prominent at short pacing cycle lengths
      (use-dependent block). 5. On the basis of present results, EGIS-7229 appears to
      carry mixed class I and class III characteristics. Class III properties are
      present at low concentrations, whereas, at higher concentrations, class I actions
      may be predominant.

PMID- 9251914
TI  - Influences of changes in calcium concentrations, cocaine and clonidine on the
      cardiac effect of acetaldehyde in rat isolated atria.
AB  - 1. Cardiovascular responses to acetaldehyde (AChO) were investigated in rat
      isolated atria. 2. Results show that two different doses of AChO (0.29 and 0.88
      mM) induce positive inotropic effects on rat atria, and express Ca2+ dependence
      when analyzed at three external Ca2+ concentrations (0.6, 1.1, 2.2 mM). 3.
      Cocaine (3.5 and 35 microM) produced significant potentiation of the AChO
      positive (0.29 and 0.88 mM) inotropic effect in 1.1 mM Ca2+ medium. 4. Clonidine
      (40 microM) increased the peak tension developed (PTD) induced by AChO (both 0.29
      and 0.88 mM) only 1.1 mM Ca2+ medium. 5. It is suggested that the positive
      inotropic effect produced by AChO involves a Ca2(+)-dependent mechanism, which
      can be potentiated by the additional stimulation of alpha-adrenergic receptors.

PMID- 9251915
TI  - Adenosine receptor agents and conditioned place preference.
AB  - 1. The effects of different doses of the adenosine agonists N5-ethylcarboxamido
      adenosine (NECA), R-isomer of N6-phenylisopropyladenosine (R-PIA), and N6
      cyclohexyladenosine (CHA) or of the antagonists theophylline and 8
      phenyltheophylline (8-PT) on conditioned place preference (CPP) have been
      studied. 2. The results show that R-PIA and CHA induced conditioned place
      aversion (CPA) whereas NECA induced conditioned place preference (CPP). 3. Low
      doses of theophylline elicit CPP, but high doses of the drug induced CPA. 8-PT
      also produced the CPP. 4. The responses of R-PIA and CHA but not NECA was
      decreased by theophylline and 8-PT administration. 5. It is concluded that the
      induction of CPP an CPA by adenosine antagonsists may be mediated by different
      adenosine receptors.

PMID- 9251916
TI  - Telecommunications in healthcare: a primer.

PMID- 9251917
TI  - Valley Force Scientific Malis CMC III bipolar electrosurgical unit activated by
      sound system remote control.

PMID- 9251918
TI  - Hazards and problems associated with home care equipment.

PMID- 9251919
TI  - Smoking and video controller board failure in Baxter-Edwards explorer monitors.

PMID- 9251920
TI  - Unclear labeling on joint replacement kits.

PMID- 9251921
TI  - Neonatal screening for congenital hypothyroidism: results and perspectives.
AB  - Systematic screening for congenital hypothyroidism in the neonate constitutes a
      major progress in the prevention of mental retardation, as the condition occurs
      in 1/4,000 newborns and necessarily results in brain damage if not properly
      detected and treated during the first days of life. Screening and diagnostic and
      therapeutic procedures are discussed, as well as outcome and prognosis of the
      affected infants. Primary thyroid-stimulating hormone screening is almost
      universally recommended. Early therapy (within 14 days) with appropriate doses of
      thyroxine (about 10 micrograms/kg/day) will prevent any brain damage even in case
      of evidence of fetal hypothyroidism, as thyroxine of maternal origin will reach
      the fetus and largely protect him. Neonatal thyroid screening is also a
      particularly sensitive monitoring tool in the evaluation of the effects and of
      the correction of iodine deficiency at the population level.

PMID- 9251922
TI  - Factors determining pubertal growth and final height in growth hormone treatment
      of idiopathic growth hormone deficiency. Analysis of 195 Patients of the Kabi
      Pharmacia International Growth Study.
AB  - A total of 195 children (117 males and 78 females) with idiopathic growth hormone
      deficiency (IGHD) treated with growth hormone (GH) for at least 1 year before
      puberty onset and who had completed treatment to adult height, were selected from
      the KIGS database for study of growth during puberty. Spontaneous and induced
      puberty started at 13.8 and 14.9 years in boys and at 12.9 and 13.7 years in
      girls, respectively. Duration of GH treatment and height gained prepubertally
      were greater when puberty was induced; prepubertal catch up growth (expressed as
      a percentage of the difference between target height and height at start of GH)
      was greater when puberty was induced in boys (59% induced vs. 45% spontaneous, p
      < 0.001), and in girls (72% induced vs. 53.9% spontaneous, p < 0.01). Final
      height was attained at 17.8 and 19.2 years in boys and at 16.0 and 17.0 years in
      girls following spontaneous and induced puberty, respectively. Final heights were
      greater after induced puberty compared with spontaneous puberty in boys (171.3
      vs. 166.0 cm, p < 0.001) and in girls (157.0 vs. 155.0 cm, n.s.). Target height
      was also significantly greater in boys with spontaneous puberty (172.2 cm vs.
      induced = 174.2 cm) as compared to girls (spontaneous = 158 cm vs. induced = 160
      cm). Duration of pubertal growth was longer in boys compared to girls (3.6 vs.
      3.0 years, p < 0.001) and was negatively correlated with age, height, and
      distance from target height at onset of puberty, but was not correlated with the
      dose of GH. Catch-up growth during puberty (expressed as a percentage of the
      difference between target height and height at puberty onset) after induced and
      spontaneous puberty was 87.9% and 80.5% (not significant) in boys and 66.4% and
      75.5% (not significant in girls. Total pubertal growth (TPG) (cm) was inversely
      correlated with prepubertal growth by simple linear regression. Multiple linear
      regression analysis indicated 5 independent predictors of TPG accounting for 78%
      of the variability, namely sex (boys grew more), distance of target height from
      height at onset of puberty (+), dose of GH at onset of puberty (+), age at onset
      of puberty (-), and age at end of growth (+).

PMID- 9251923
TI  - Short-term changes in urinary growth hormone excretion and lower leg length in
      healthy children.
AB  - To investigate any association between changes in lower leg length (LLL) and
      urinary growth hormone (uGH) excretion, 4 prepubertal children supplied daily 12
      hour overnight urine samples and had daily knemometry performed for 4 weeks. The
      mean daily and weekly LLL velocity (LLLV) of the group was (0.08 mm/day (95% CI
      0.01-0.18) and 0.52 mm/week (range 0.38-0.78), respectively. The mean uGH
      excretion was 8.9 ng/l (CI 3.7-13.3), and the mean intrasubject coefficient of
      variation of uGH was 55% (range 32-93). The tallest subject who also had the
      highest LLLV excreted the least amount of uGH (mean 3.7 ng/l, CI 2.9-4.5). No
      temporal relationship was evident between daily uGH excretion and LLLV. There was
      no evidence of any association between amount of uGH excreted and LLLV. There
      remains some doubt on the usefulness of uGH measurement as the sole predictor of
      normal GH production.

PMID- 9251925
TI  - Pubertal changes in testicular 3 beta-hydroxysteroid dehydrogenase activity in a
      male with classical 3 beta-hydroxysteroid dehydrogenase deficiency showing
      spontaneous secondary sexual maturation.
AB  - Males with classical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency
      manifest appropriate secondary sexual maturation with an elevation in serum
      testosterone levels at pubertal age. To define the origin of serum testosterone,
      we evaluated a male patient with classical 3 beta-HSD who showed pubertal
      development. High values of testosterone and a ratio of delta(5) to delta(4)
      steroids in the spermatic vein indicated direct production of considerable
      amounts of testosterone and a persistent defect of 3 beta-HSD activity in the
      gonad. Immunohistochemical analysis showed distinct immunoreactivity in the
      Leydig cells of the patient. The patient was homozygous for a nonsense mutation
      in the type-II 3 beta-HSD gene. We propose that gonadal type-I 3 beta-HSD could
      be expressed by gonadotropin stimulation at pubertal age, and delta(4)-steroid
      precursors would convert to testosterone.

PMID- 9251924
TI  - Insulinoma associated with a case of multiple endocrine neoplasia type I:
      Functional somatostatin receptors and abnormal glucose-induced insulin secretion.
AB  - A sporadic case of multiple endocrine neoplasia type I with coexisting insulinoma
      and hyperparathyroidism was investigated in vivo and in vitro. The insulinoma was
      localized by somatostatin receptor scintigraphy and these receptors were
      functionally active. Octreotide administration decreased the basal insulin and
      glucagon secretion by 90 and 46%, respectively. Immunocytochemistry of the
      insulinoma tissue was positive for insulin, chromogranin A and neuropeptide Y.
      The insulinoma cells were also isolated and cultured in vitro. Incubation
      experiments revealed that a low glucose concentration (1 mmol/l) was sufficient
      to increase cytosolic free calcium and to produce a maximal glucose-induced
      insulin release. Northern blot analysis of RNA obtained from the tumor showed a
      high abundance of the low Km glucose transporter GLUT1 but no transcript for the
      high Km glucose transporter GLUT2. The abnormal distribution of glucose
      transporters probably relates to the abnormal glucose sensing of insulinoma
      cells, and explains their sustained insulin secretion at low glucose
      concentrations. Whether these abnormalities share a pathogenetic link with the
      presence of functionally active somatostatin receptors remains to be elucidated.

PMID- 9251927
TI  - Alzheimer's Disease International.

PMID- 9251926
TI  - Effect of metformin on glucose disposal and hyperinsulinaemia in a 14-year-old
      boy with acanthosis nigricans.
AB  - We report the treatment of a 14-year-old Indian boy with acanthosis nigricans and
      hyperinsulinaemia with metformin in an attempt to improve his skin lesions. Oral
      metformin was used for 6 months with assessment of insulin status during an
      intravenous glucose tolerance test and hyperinsulinaemic-euglycaemic clamping
      before and after treatment. The first-phase insulin response reduced from 19,593
      to 5,410 pmol/l/min (normal 1,900-13,400), and the second-phase insulin response
      improved from 59,120 to 34,020 pmol/l/min (normal 2,900-18,100). During
      hyperinsulinaemic-euglycaemic clamping hepatic glucose production was normally
      suppressed prior to therapy, but peripheral glucose remained abnormally low, 152
      and 138% of basal (expected 199%). The acanthosis nigricans remained unaltered
      but over this period puberty progressed and his body mass index increased. We
      conclude that, in this patient, metformin had a minimal effect on the
      hyperinsulinism and none on the acanthosis nigricans in the relatively short
      term, but further studies in more patients over longer time intervals are
      warranted.

PMID- 9251928
TI  - Alzheimer's disease in Poland.

PMID- 9251929
TI  - Sexual expression and dementia. Views of caregivers: A pilot study.
AB  - OBJECTIVE: To measure the attitudes of health professionals in nursing homes
      towards sexuality and sexual expression in cognitively impaired and cognitively
      intact residents. DESIGN: Postal survey. PARTICIPANTS: The staff (administrators,
      clinicians, social workers and others) of 300 randomly selected nursing homes
      located in three states. Of these, 114 representatives responded. MAIN OUTCOME
      MEASURE: A measure of attitudes towards resident sexuality developed during a
      prior study. RESULTS: Results suggest that respondents held a generally positive
      orientation towards residents' sexual expression which was expressed with respect
      to cognitively impaired residents as well as to those who were cognitively
      intact. Possibly because of the small sample size and resulting low statistical
      power, statistical analyses failed to demonstrate any significant differences
      among the groups of residents: administrators, clinicians, social workers, and
      undifferentiated 'others'. However, while non-significant, there was a consistent
      tendency for administrators to be relatively more conservative than were the
      other groups. Almost all respondents agreed that additional staff training should
      focus specifically on dealing with resident sexual expression. CONCLUSIONS:
      Overall, the sample reported generally positive attitudes towards resident
      sexuality and sexual expression.

PMID- 9251930
TI  - Prevalence of dementia in a rural setting: A report from India.
AB  - A study to estimate the prevalence of dementia in a rural population was
      conducted in a community located on the outskirts of Madras city in South India.
      Seven hundred and fifty elderly 60 years of age and older, selected using the
      cluster sampling technique, were interviewed using the Geriatric Mental State
      schedule (GMS). The prevalence of dementia was 3.5%, the percentage increasing
      with age. These rural prevalence estimates were higher than in urban settings
      (WHO multicentre study on cognitive impairment and dementia in developed and
      developing countries, unpublished) and male/female differences were negligible.
      The difficulties associated with the use of the GMS in a non-literature rural
      population are discussed. The implications of these findings for India's growing
      elderly population are highlighted.

PMID- 9251931
TI  - Ageing and senility: a major problem of psychiatry. Aubrey Lewis, Journal of
      Mental Science (1946), 92: 150-170.

PMID- 9251932
TI  - Schizophrenia with onset at the extremes of adult life.
AB  - OBJECTIVE: To define the epidemiology, phenomenology, premorbid and risk factors
      in patients with the first manifestation of a schizophrenia-like illness after
      the age of 60 years, and compare them with patients with an onset before the age
      of 25 years. DESIGN/SETTING/SUBJECTS: All contacts for a non-affective psychotic
      illness across all ages of onset were ascertained through a psychiatric case
      register; patients were rediagnosed according to operationalized criteria for
      psychotic illness, and those with a very early and very late onset compared. MAIN
      OUTCOMES MEASURES: Phenomenological, premorbid and aetiological parameters were
      compared in the two groups, using risk ratios and 95% confidence intervals.
      RESULTS: Very late onset patients (N = 72) were, compared to their very early
      onset counterparts (N = 192), more likely to be female, have good premorbid
      functioning and development history, and to exhibit persecutory delusions and
      hallucinations; they were less likely to have negative schizophrenic symptoms, to
      have a positive family history of schizophrenia, or have suffered pregnancy or
      birth complications. CONCLUSIONS: The results highlight premorbid, aetiological
      and phenomenological differences between patients with the onset of a
      schizophrenia-like illness at the extremes of adult life, and suggest it is
      premature to consider the two groups to be merely different manifestations of the
      same illness.

PMID- 9251933
TI  - The relationship between patient behaviour and environmental quality for the
      dementing.
AB  - BACKGROUND: The quality of long-term hospital care for demented patients has
      never been studied in relation to the behaviour of the residents, although this
      relationship has been studied for other patient groups and in other settings.
      METHOD: Five aspects of environmental quality were assessed using a rating scale
      package. Seven wards with a range of quality were selected and patient behaviour
      categorized and recorded using a direct observation method. RESULTS: Comparative
      analyses revealed that institutional ward practices were associated with abnormal
      motor activity and inappropriate behaviour. In addition, social/recreational
      provision was associated with increased social behaviour and less time spent
      doing nothing, although high levels of provision were also associated with
      abnormal motor activity and inappropriate behaviour. Inappropriate behaviour also
      appeared to be related to a lack of provision of reality orientation cues and to
      better quality of ward condition. Space availability was not associated with any
      behavioural patterns. CONCLUSIONS: Some aspects of the environment are associated
      with patterns of behaviour. There is a need for further research both in this
      setting and in non-hospital settings.

PMID- 9251934
TI  - The elderly homeless men in Bloomsbury hostels: their needs for services.
AB  - OBJECTIVES: The objectives of this study are: (1) to assess the feasibility and
      usefulness of using the Needs Schedule on older homeless individuals; (2) to
      measure the needs of the elderly homeless individual for mental health services
      and whether these needs could be met by the same services that cater for younger
      individuals. DESIGN AND SETTING: This article analyses the needs of a subsample
      of 37 elderly residents in four inner London hostels for homeless people. Their
      needs were compared with those of 64 younger residents within the same hostels.
      RESULTS: The data related to demographic characteristics and health problems
      showed that the elderly homeless were physically frail and socially isolated.
      This group demonstrated more need for physical health services than the younger
      sample. However, the needs assessment method used in this study failed to show
      significant differences between the needs of these elderly and those of the
      younger residents. CONCLUSIONS: The article discusses ways of improving the
      assessment of needs for services in the elderly homeless and the way forward in
      meeting the needs of this disadvantaged group.

PMID- 9251935
TI  - Psychiatric morbidity among the elderly in a primary care setting--report from a
      survey in Sao Paulo, Brazil.
AB  - Brazil has been experiencing a steady increase in the elderly population during
      the past few years, and as a result old age health-related problems are
      increasing continuously in number. Psychiatric symptoms are among the most
      prevalent health problems of the elderly and are an important source of distress
      for patients and carers, being also associated with significant growth in the
      costs and demand for the provision of health care services. This study aimed to
      investigate the prevalence of mental health problems among the elderly attending
      a regional primary care unit in the city of Sao Paulo, Brazil. A total of 351
      patients older than 60 were assessed during a 6-month period with the SRQ-20 (a
      scale for the detection of minor psychiatric problems), four questions on
      psychotic symptoms. AMTS (a scale for the assessment of cognitive functioning)
      and CAGE (a scale for the assessment of alcoholism); demographic variables were
      also recorded. Subjects' mean age was 71.22 (CI = 70.51-71.92) and 83.5% were
      female. Thirty-two per cent of subjects were considered 'cases' as they scored
      more than 7 on the SRQ-20 (26.8% of total), or more than 1 on the CAGE (1.4% of
      total), or at least 1 on the questions assessing psychotic symptoms (12.2% of
      total). There was a significant excess of women among those found to suffer from
      psychiatric problems (90.1% vs 80.4%). Cases were also more likely to be
      illiterate (23.4% vs 12.1%) and to have a lower income (2.21 vs 4.01 minimum
      wages). Depressive symptoms and tension were highly prevalent (72.9% of
      subjects). Somatic complaints and signs of inefficient functioning were also
      common (50.4% and 45.9% respectively). Only five patients answered affirmatively
      two or more CAGE questions and 12.2% scored at least 1 on the questions assessing
      psychotic symptoms. Cognitive deficit, as determined by the AMTS, was observed in
      13.4% of the sample and was associated with ageing, being illiterate and having
      higher total SRQ-20 scores. We suggest, that the organization of health care
      services should take into account the needs of this population, and should also
      emphasize professional training for the correct assessment and treatment of the
      most frequent mental health problems in old age.

PMID- 9251936
TI  - Psychological distress among informal supporters of frail older people at home
      and in institutions. The Resource Implications Study Group of the MRC Cognitive
      Function and Ageing Study.
AB  - OBJECTIVE: Investigate presence of psychiatric morbidity in informal carers using
      30-item General Health Questionnaire (GHQ) and examine which factors best predict
      psychiatric morbidity. DESIGN: Two-year longitudinal, panel survey of informal
      supporters of frail elderly subjects, using semi-structured interview schedules.
      Subjects were those defined as frail after screening stratified random sample of
      people aged 65 or over. SETTING: Informal supporters of frail elderly subjects
      residing in private households or residential or nursing homes in four UK
      districts. RESPONDENTS: 623 informal supporters of subjects living at home, 129
      regular visitors of those in long-term care. MEASURE: 30-item GHQ (cross
      sectional analysis). RESULTS: Stepwise multiple regression indicated main
      predictors of high GHQ scores in key supporters were: subjects had at least three
      problems of behaviour (b = 1.56, 95% CI 1.25-1.94); supporters had to alter
      working hours (b = 1.70, 95% CI 1.15-2.51); supporters were female (b =1.26, 95%
      CI 1.06-1.50). The following variables predicted low GHQ scores: supporters able
      to leave subject all day (b = 0.71, 95% CI 0.64-0.80); subjects never wandered (b
      = 0.78, 95% CI 0.62-0.99); supporters were 'other relatives' or friends of
      subject (b = 0.74, 95% CI 0.59-0.91). For visitors, spouses were most likely to
      have high GHQ scores (b = 2.46, 95% CI 1.32-4.57). CONCLUSIONS: Results suggest
      the need for greater collaboration between formal and informal care. Little work
      has been carried out to ascertain which interventions are most effective in
      alleviating carer stress: a series of randomized controlled trials to determine
      long-term effectiveness of various interventions for different groups of carers
      is required.

PMID- 9251938
TI  - Does hospital admission affect dependency levels of elderly psychiatric patients?
AB  - OBJECTIVE: To study effect of hospital admission on dependency levels of
      psychogeriatric patients. DESIGN: A cohort was formed comprising consecutive
      admissions. This was subdivided into organic and functional cases and the
      dependency levels of the two groups compared on admission and discharge. SETTING:
      An acute psychogeriatic ward at a psychiatric hospital near London. PATIENTS: One
      hundred consecutive acute elderly psychiatric inpatients. MEASURES: The Stockton
      Geriatric Rating Scale was used to assess dependency levels, the Hamilton Rating
      Scale for Depression and the Mini-Mental State Examination for cognitive
      impairment. RESULTS: Patients with functional illness showed a significant
      reduction in dependency levels compared to organic cases during admission.
      CONCLUSION: Admission to hospital has a significant effect in reducing dependency
      levels of elderly patients with functional illness.

PMID- 9251937
TI  - Tolerability of clonazepam in demented and non-demented geropsychiatric patients.
AB  - OBJECTIVE: The tolerability of clonazepam in geropsychiatric inpatients was
      examined in patients with and without a diagnosis of dementia. DESIGN: Forward
      looking retrospective study comprising consecutive patients placed on clonazepam.
      SETTING: A geropsychiatry unit of a large Veterans Affairs Medical Center.
      PATIENTS: All geropsychiatry inpatients placed on clonazepam over a 21-month
      period of time. MEASURE: Mini-Mental State Examination, Brief Psychiatric Rating
      Scale, Cohen-Mansfield Agitation Inventory and the Rating Scale for Side Effects
      were performed at admission and discharge as part of an ongoing database.
      RESULTS: Twenty-four geropsychiatric inpatients were treated with clonazepam
      (mean dose of 1.2 mg for a minimum of 2 weeks) during the 21 months studies.
      About one half of the patients had a primary diagnosis of dementia and the
      remainder had a diagnosis of an affective or psychotic disorder. Two of these
      patients were discontinued because they had responded to the acute need for
      clonazepam and a third patient was discontinued because of the development of
      sedation and confusion. For the remaining 21 patients, scores improved
      significantly on the Brief Psychiatric Rating Scale (p = 0.017), the Cohen
      Mansfield Agitation Inventory (p = 0.011), the Rating Scale for Side Effects
      (0.004) and the Global Assessment of Functioning (p < 0.000), with no differences
      in amount of improvement between demented and non-demented patient groups. Scores
      on the Mini-Mental State Examination remained unchanged. CONCLUSIONS: Clonazepam
      shows promise as a benzodiazepine with good tolerability in the elderly.

PMID- 9251939
TI  - Profiling the care needs of the population with dementia: a survey in central
      Scotland.
AB  - OBJECTIVE: To demonstrate a low-cost method of producing local information for
      dementia service planning. DESIGN: (1) Multiservice census. (2) Stratified random
      sample survey (stratified by setting) to assess needs. SETTING: All community and
      institutional settings in Forth Valley Health Board area. PARTICIPANTS: (1)
      People age 65 + defined by health and social care professionals as having
      'problems of memory/confusion (as is caused by dementia)' (N = 2060). (2) As (1)
      excluding those with score < 2 on Levin's checklist and no relevant known
      diagnosis (N = 286). MAIN OUTCOME MEASURES: Coverage of population with dementia
      against EURODEM prevalence. Place of residence of sufferers. Level of care needs.
      MAIN RESULTS: Identified population, pro-rating for identifiable non-response,
      accounted for 78% of EURODEM prevalence. Assuming unidentified 22% to live at
      home, 45% of total population with dementia were in some form of institutional
      care. Survey demonstrated high levels of need in local population with dementia
      known to services. Assistance was required more than once a day with mobility by
      48%, personal care by 60%, domestic tasks by 75% and because of behavioural
      problems by 57%. Assistance was required at night by 59% because of personal care
      needs and by 54% because of behaviour problems. CONCLUSIONS: The value of a broad
      based survey 'snapshot' across the range of settings was confirmed. It can be
      accomplished relatively quickly and cheaply and complements information collected
      in other ways.

PMID- 9251940
TI  - Factor structure of the Hamilton Rating Scale for Depression in a cohort of
      community-dwelling elderly.
AB  - We examined the factor structure of the 17-item Hamilton Rating Scale for
      Depression (HRS-D) in 206 community-dwelling elderly patients. Using principal
      components analysis and quartimax rotation, a four-factor structure involving all
      17 items and accounting for 57.7% of the variance was desired. The factors
      represented the following dimensions of depressive symptomatology and illness:
      depressed affect, vegetative symptoms, anxiety, and agitation/insight. This
      factor structure reflects the presentation of depressive symptomatology and
      depressive illness in this population. Findings suggest that the HRS-D can be
      used for clinical assessment of depressive symptomatology along major dimensions
      of depressive illness in community-dwelling elderly.

PMID- 9251941
TI  - Partnership nursing home care for dementia: the Glasgow experience--one-year
      follow-up.
AB  - The outcome of the transfer of 60 elderly patients suffering from dementia from
      hospital to nursing home care under a partnership contract was reviewed at 6 and
      12 months following transfer. The nursing home population had fared badly
      compared with patients remaining in hospital during the first 3 months. This
      difference was less evident at 6 months follow-up and had disappeared at 12
      months follow-up. It seems that a partnership agreement such as this can deliver
      a quality of health care at least as good as hospital treatment as long as the
      transfer is handled carefully.

PMID- 9251942
TI  - Outcome of nursing home care for residents with alcohol use disorders.
AB  - OBJECTIVES: To describe the outcome of nursing home (NH) care for a previously
      established cohort of residents with active, inactive or no alcohol use disorder
      (AUD), and to examine demographic variables, health services utilization,
      mortality and drinking behaviors in this group. DESIGN: Retrospective cohort
      study with participant interviews at NH admission and 3 years later. SETTING:
      Urban Veterans Affairs (VA) Medical Center and Nursing Home Care Unit (NHCU).
      PARTICIPANTS: Patients older than age 50 admitted consecutively to a VA NHCU
      between July 1991 and February 1993 who completed a structured interview, N =
      117. MAIN OUTCOME MEASURES: AUD as determined by DSM-III-R criteria.
      Demographics, health services utilization and mortality as abstracted from the VA
      medical record. RESULTS: Health service utilization as measured by care episodes
      was not significantly different in the three groups (active, inactive and no
      AUD), but subjects with AUD had documented health services use related to
      alcoholism, including hospitalizations for alcohol-related illness, placements in
      long-term care facilities to control drinking and death from alcohol-related
      causes. The mean age at death was significantly younger for study participants
      with active or inactive AUD compared to those with no AUD: 67.7, 70.4 and 77.9
      years, respectively (p < 0.004). Of the 21 participants with active AUD at NHCU
      entry, 11 resumed drinking after discharge and six still met criteria for active
      AUD 3 years later. CONCLUSIONS: The subset of NHCU patients with active AUD
      continued to incur alcohol-related hospitalizations and institutionalizations
      following NHCU discharge and suffered early mortality relative to their peers.
      Effective models of care for this subset of patients should be sought.

PMID- 9251944
TI  - Current awareness in geriatric psychiatry.

PMID- 9251943
TI  - The elderly in a period of transition in Sofia.

PMID- 9251945
TI  - Outcomes of multifetal pregnancy reduction in multiple pregnancies achieved by
      intracytoplasmic sperm injection using ejaculated, testicular, or epididymal
      sperm.
AB  - OBJECTIVE: To report the pregnancy outcome after transabdominal multifetal
      pregnancy reduction in multiple pregnancies achieved by intracytoplasmic sperm
      injection. METHODS: One twin and 13 triplet pregnancies obtained by
      intracytoplasmic sperm injection underwent pregnancy reduction. Pregnancies were
      achieved with ejaculated sperm in 8, testicular sperm in 3, and epididymal sperm
      in 2 of these cases. All triplet pregnancies were reduced to twins at 10-12
      weeks' gestation by transabdominal potassium chloride injection. A twin pregnancy
      with spina bifida affecting 1 fetus was reduced to singleton at 18 weeks of
      pregnancy. RESULTS: There was no failed procedure and no pregnancy loss within
      the first 4 weeks after the procedure. A complete miscarriage (7.1%) developed in
      1 case at 17 weeks' gestation which was due most probably to the incompetent
      cervix. In utero fetal death occurred in 1 fetus of another reduced pregnancy.
      Three of the reduced pregnancies delivered at term, after 37 completed weeks,
      four premature deliveries occurred between 31 and 35 gestational weeks, and four
      pregnancies were ongoing beyond 25 weeks' gestation. A total of 16 fetuses, from
      seven twin and two singleton pregnancies, were delivered without perinatal
      mortality. CONCLUSIONS: Although the sample size was small, our experience
      indicates that the reduction of triplets obtained by sophisticated infertility
      treatments such as intracytoplasmic sperm injection using testicular or
      epididymal sperm seems to be a safe method and can be effectively used.

PMID- 9251946
TI  - Islet amyloid polypeptide (amylin) does not seem to be directly involved in the
      development of gestational diabetes mellitus.
AB  - In order to define the islet amyloid polypeptide (IAPP) levels in gestational
      diabetes mellitus (GDM) and their interrelationship with the insulin levels, we
      studied (1) the placental RNA from 10 women (5 with GDM and 5 normals) for IAPP
      expression by Northern blotting and (2) 10 women with GDM during a 100-gram oral
      glucose tolerance test and compared these with 11 normal women matched for
      obesity and age. Plasma levels of glucose, IAPP, insulin, and C peptide were
      determined. No IAPP expression was detected in any of the placentae after a long
      exposure. We could not demonstrate any differences in plasma IAPP levels (basal
      or stimulated) between the two groups of pregnant women. However, in women with
      GDM we found a lower IAPP/insulin ratio (p < 0.05) and a lower maximal
      IAPP/maximal insulin response ratio during the oral glucose tolerance test (p <
      0.05) than in normal women. Therefore, IAPP does not appear to be directly
      involved in the development of GDM. The peripheral levels of IAPP relative to
      insulin are lower in GDM, a finding similar to that described in type 2 diabetes
      mellitus (non-insulin-dependent diabetes mellitus). This observation further
      confirms that GDM resembles the early stages of type 2 diabetes mellitus.

PMID- 9251947
TI  - Hypertensive disorders in pregnant women with diabetes mellitus.
AB  - The present study was performed to assess the rate of hypertensive complications
      in diabetic pregnant patients and the influence of White's classification and the
      quality of the diabetic control. This study included 169 diabetic pregnant women
      who had delivered at the University Hospital of Botucatu Brazil from 1980 to
      1981. The hypertensive disorders occurred in 29.8% of the cases. The incidence of
      the hypertensive process was the same in all classes of diabetic patients, and it
      was independent of the glycemic control. In patients with gestational diabetes
      (classes A and AB), chronic hypertension was the commnest type found; in patients
      with short-term diabetes (classes B and C) pregnancy-induced hypertension (PIH)
      and chronic hypertension with superimposed PIH was the most frequent type, and
      diabetic patients with vasculopathies (classes D-R) had preeclampsia and chronic
      hypertension with superimposed preeclampsia as the commonest type found.

PMID- 9251948
TI  - Microorganisms in vaginal fluid from women in prolonged pregnancy.
AB  - In order to compare the vaginal microflora of women in prolonged pregnancy with
      that of women who delivered at term, samples for quantitative aerobic and
      anaerobic microbiological culture were collected from 100 women at 42 weeks of
      gestation and from 60 women at term. The occurrence of lactobacilli-dominated
      flora was similar in women at term and women with prolonged pregnancy. However,
      non-hydrogen-peroxide-producing lactobacilli (p < 0.01) were significantly more
      common and Peptostreptococci species (p < 0.05) significantly less common in
      postterm women as compared with term controls. In postterm women, Candida
      albicans was more common (p < 0.001) in microfloras dominated by non-hydrogen
      peroxide-producing lactobacilli than in floras dominated by hydrogen-peroxide
      producing lactobacilli. The ecosystem of the vagina in asymptomatic postterm
      women was disrupted concerning the composition of lactobacilli as compared with
      term controls.

PMID- 9251949
TI  - Ampicillin/sulbactam versus cefotetan for the prevention of infection following
      cesarean delivery in high-risk patients: a randomized double-blind trial.
AB  - The objective of this study was to compare the efficacy and safety of a single
      intravenous dose of 1 g ampicillin plus 0.5 g sulbactam to a single intravenous
      dose of 1 g cefotetan in the prevention of postoperative infection following
      cesarean delivery in high-risk patients. In this single-center comparative study,
      women who were to undergo cesarean delivery and who were at high risk of
      developing postoperative infection were randomized into two treatment groups. At
      the time the umbilical cord was clamped, one group was treated intravenously with
      1 g ampicillin plus 0.5 g sulbactam, and the other was treated intravenously with
      1 g cefotetan. The two groups were evaluated for evidence of postoperative
      infections and adverse experiences. A total of 170 women who were at high risk of
      developing postoperative infection following cesarean delivery (87 in the
      ampicillin/sulbactam group and 83 in the cefotetan group) were analyzed.
      Successful prophylaxis, absence of any infection including absence of febrile
      morbidity with no other symptoms, was reported in 69 of 87 (79%) patients
      receiving ampicillin/sulbactam and in 60 of 83 (72%) patients receiving
      cefotetan. One patient in each group had an infection at the incision site. There
      were no statistically significant differences in the rates of endometritis or
      urinary tract infections. The mean duration of hospitalization was 5.5 days for
      patients receiving ampicillin/sulbactam and 5.7 days for patients receiving
      cefotetan. A single intravenous dose of the combination of ampicillin/sulbactam
      was as safe and effective as a single intravenous dose of cefotetan when
      administered for the prevention of infections following cesarean delivery in
      patients at high risk of developing postoperative morbidity. Both antibiotics
      were safe and well tolerated with no unusual or unexpected events.

PMID- 9251950
TI  - Fetal heart rate decelerations precede a decrease in fetal oxygen content.
AB  - To determine the relationship between abnormal fetal heart rate (FHR) patterns,
      fetal oxygen content by reflectance pulse oximetry, and the effects of maternal
      oxygen administration, 158 intrapartum women consisting of 120 women with normal
      FHR patterns, and 38 women with varying degrees of variable FHR decelerations
      were examined. A new reflectance pulse oximetry probe was attached to the fetal
      forehead to continuously monitor fetal oxygen saturation (SpO2) during labor.
      Oxygen was administered for 30 min at 5 liters/min by nasal canula in 32 women.
      No significant change in fetal SpO2 was seen in women with normal FHR patterns,
      but a significant decline in SpO2 was observed shortly before births. FHR
      decelerations less than 90 bpm occurred prior to the decline in fetal SpO2.
      Maternal oxygen administration was effective in increasing fetal SpO2 in fetuses
      with decreased SpO2 (SpO2 < 50%), but not in fetuses with high SpO2 (SpO2 > 60%).
      It is concluded that fetal SpO2 exhibits no change during normal labor but
      significantly declines shortly before birth, that relatively severe variable
      decelerations (<90 bpm) can decrease fetal SpO2, and that maternal oxygen
      treatment at 5 liters/min is effective in augmenting fetal oxygen tension in
      fetuses with decreased oxygen tension.

PMID- 9251951
TI  - Local immune response in infertile patients with minimal endometriosis.
AB  - OBJECTIVE: To evaluate the role of local immunity in women with minimal
      endometriosis. METHODS: Uterine endometrium and endometrial implants were
      obtained simultaneously from 30 infertile women with minimal endometriosis and
      examined immunohistochemically using antibodies of T cell, B cell, macrophage,
      Langerhans cell, immunoglobulin (Ig)G, and complement (C) 3d. Serum IgG, IgA,
      IgM, C3, C4, antinuclear antibody and anti-DNA antibody were also examined in 24
      of the women. Data from uterine endometrium and serum were compared with 10
      fertile women without endometriosis as a control. RESULTS: Microscopic
      examination revealed that the endometrial implants were divided into two groups:
      group 1 (n = 13) showed lymphocytic infiltration in the endometrial implants and
      group 2 (n = 17) showed no or slight lymphocytic infiltration. The endometrial
      implants of group 1 showed significantly more dense T-cell infiltration than
      those of group 2. Other types of infiltrating cells and deposits of IgG and C3d
      revealed no significant differences between groups 1 and 2. The
      immunohistochemical examination of the uterine endometrium and the serum data
      revealed no significant differences among all three groups. Cumulative pregnancy
      rates showed no significant difference between groups 1 and 2. CONCLUSION: The
      difference of local immune response in endometrial implants did not affect
      systemic immunity.

PMID- 9251952
TI  - Laparoscopic laser treatment for endometriosis.
AB  - The advent of the use of laparoscopy and lasers in gynaecology has added a
      further option for the treatment of endometriosis. This study is a retrospective
      review of the notes of 28 women who had endometriosis treated laparoscopically
      with an Nd:YAG laser. Results were assessed by subjective reporting of symptoms.
      Seventy-three percent of patients reported significant or complete resolution of
      symptoms at three to 26 months follow-up. No major complications were
      encountered. The results suggest this offers a further treatment option for
      endometriosis which merits further evaluation.

PMID- 9251953
TI  - Regional distribution of proliferating cells and hormone receptors in the mammary
      gland of surgically postmenopausal macaques.
AB  - OBJECTIVE: To define the relative proliferative response and hormone receptors
      status in ten sites in the mammary gland of surgically postmenopausal cynomolgus
      macaques given hormone replacement therapy. METHODS: Surgical postmenopausal
      cynomolgus macaques were given either no treatment (n = 4), conjugated equine
      estrogens (CEE, n = 4), or combined therapy with CEE and medroxyprogesterone
      acetate (n = 4). The drugs were administered in the diet, at doses equivalent on
      a caloric basis to 0.625 mg/woman/day for CEE and 2.5 mg/woman/day for
      medroxyprogesterone acetate. Immunostaining of mammary sections was done for
      estrogen receptor, progesterone receptor, and the proliferation marker Ki-67 MIB
      1 (MIB). Comparisons were made between central and peripheral gland, by quadrant,
      left versus right, and with respect to distance from the nipple within each
      quadrant. RESULT: There were no significant differences in hormone receptor or
      MIB expression within different sites within the gland. CONCLUSIONS: In the
      surgically postmenopausal, hormone-treated macaque, regional differences in
      estrogen and progesterone receptors and MIB staining are not apparent. The
      assumption of homogeneity throughout the gland makes aspiration cytology and
      multiple biopsy studies feasible in this species.

PMID- 9251954
TI  - Effects of 17beta-estradiol and progesterone on the adhesion of human monocytic
      THP-1 cells to human female endothelial cells exposed to minimally oxidized LDL.
AB  - It is known that hormone replacement therapy inhibits the progression of
      atherosclerosis in postmenopausal women. Focal attachment of monocytes to
      endothelial cells is observed in early atherosclerotic lesions. The aim of this
      study was to investigate the effects of 17beta-estradiol (E2) and progesterone on
      the adhesion of human monocytic THP-1 cells to human female aortic endothelial
      cells (HAECs) in vitro. Minimally oxidized low-density lipoprotein (LDL)
      significantly increased THP-1 cell adhesion to HAECs as compared with native LDL
      at the same concentration. Though E2 inhibited minimally oxidized LDL-induced THP
      1 cell adhesion in a dose-dependent manner, progesterone had no significant
      effects. Preincubation of HAECs with tamoxifen significantly antagonized the
      inhibitory effect of E2. These findings suggest a beneficial effect of hormone
      replacement therapy on atherosclerosis.

PMID- 9251955
TI  - Combination of subtotal perineoplasty and interferon for the treatment of vulvar
      vestibulitis.
AB  - PURPOSE: To evaluate the efficacy of a combination of subtotal perineoplasty and
      interferon (IFN) infiltration of the remaining anterior vestibule in the
      treatment of vulvar vestibulitis. BASIC PROCEDURES: Nineteen women with vulvar
      vestibulitis were randomized to undergo either a total perineoplasty or a
      subtotal perineoplasty without removal of the anterior vestibule. The second
      group was further treated 6 weeks later with injection of the anterior vestibule
      by IFN. Differences in outcome between the groups were analyzed using Fisher's
      exact test. MAIN FINDINGS: The combination of subtotal perineoplasty and IFN
      injections was successful in 7 of 10 women, similar to the outcome of the group
      undergoing total perineoplasty (6 of 9 patients). CONCLUSION: A combination of
      subtotal perineoplasty and IFN injections to the anterior vestibule is as
      effective as total perineoplasty and has less surgical complications.

PMID- 9251957
TI  - Prenatal diagnosis of tetralogy of Fallot with absent pulmonary valve accompanied
      by hydrops fetalis.
AB  - Tetralogy of Fallot with absent pulmonary valve is a rare congenital cardiac
      anomaly. We report on the echocardiographic features of a fetus with such an
      anomaly and aneurysm of the pulmonary artery associated with hydrops fetalis and
      polyhydramnios. The prognosis of tetralogy of Fallot with absent pulmonary valve
      and pulmonary aneurysm is grave, especially in a fetus with intrauterine heart
      failure. Serial sonographic follow-up is mandatory to detect the signs of hydrops
      fetalis. Early intervention and intensive treatment should be given to improve
      the perinatal outcome once the prenatal diagnosis is made.

PMID- 9251956
TI  - Clinical responses and platinum concentrations in tumors after intra-arterial and
      intravenous administration of cisplatin in the same patients with cervical
      cancer.
AB  - We evaluated 3 patients with advanced cervical cancer treated with cisplatin
      intra-arterially and intravenously. The dose of cisplatin was 50 mg/m2 in each
      infusion. Chemotherapy was repeated at 4-week intervals for three to four
      courses. The clinical response and the tumor concentration of platinum were
      evaluated in each course. All patients who received the intra-arterial infusion
      of cisplatin were judged to be responders, whereas none of them responded to the
      intravenous infusion. The platinum concentration in tumor tissue was
      significantly higher after intra-arterial infusion of cisplatin (1.97 +/- 0.04
      vs. 2.86 +/- 0.10 microg/g). Although there were no apparent differences in side
      effects between intra-arterial and intravenous routes, 2 of 3 patients rejected
      an intra-arterial route. The present study suggests that intra-arterial
      administration of cisplatin may be useful in treating locally advanced cervical
      cancer.

PMID- 9251958
TI  - Successful treatment of cornual pregnancy by local injection of methotrexate
      under laparoscopic and transvaginal ultrasonographic guidance.
AB  - This report describes a woman with cornual pregnancy, documented by
      ultrasonography and laparoscopy, who was successfully treated with two doses of
      methotrexate under laparoscopic and ultrasonographic guidance. The serum beta
      human chorionic gonadotropin level was 20,000 mIU/ml and increased to 43,800
      mIU/ml after the first methotrexate injection and to 44,400 mIU/ml after second
      injection and fell precipitously to nonpregnant levels within 27 days. No side
      effects were experienced by the patient.

PMID- 9251959
TI  - Langerhans cell histiocytosis of vulva and cervix in a 19-year-old woman.
AB  - Langerhans cell histiocytosis of the female genital tract is a rare disease. A
      clinical diagnosis is impossible to establish because no typical lesions are
      found. Immunohistochemistry of bioptic samples is the easier technique to obtain
      the correct diagnosis. We present a case of a 19-year-old woman with Langerhans
      cell histiocytosis of mandible and maxilla with subsequent cervical and vulvar
      histiocytosis.

PMID- 9251960
TI  - Treatment of metastatic uterine leiomyosarcoma with cisplatin, pirarubicin, and
      ifosfamide.
AB  - We present the unusual case of a 27-year-old Japanese woman who exhibited
      recurrences of metastatic tumors from uterine leiomyosarcoma after five
      operations. Chemotherapy with cisplatin, pirarubicin, and cyclophosphamide was
      ineffective. Substituting ifosfamide for cyclophosphamide, we obtained a complete
      response. The Gynecologic Oncology Group (GOG) in the United States has
      recognized the efficacy of ifosfamide and mesna in the treatment of patients with
      advanced or recurrent uterine sarcomas. Here we report on the efficacy of
      ifosfamide in addition to cisplatin and pirarubicin.

PMID- 9251961
TI  - The effect of vocalization on the heart rate response to mental arithmetic.
AB  - The heart rate (HR) responses to verbal and nonverbal mental arithmetic tasks
      were studied in twenty undergraduate males. The two problem-sets were presented
      in counterbalanced order to the subjects. Greater HR responses to verbal, in
      contrast to nonverbal, arithmetic were only observed when the verbal arithmetic
      task was presented first. The peak (maximal) HR response was also the highest
      when the verbal arithmetic was presented first to the subjects. It is concluded
      that physiological or mechanical components of vocalization do not affect the HR
      response to mental arithmetic. However, certain psychological components,
      including test-anxiety or motivation, may increase the HR when subjects have to
      provide verbal answers during a first exposure to a challenge. This effect
      dissipates during the second exposure to the challenge due to habituation.

PMID- 9251962
TI  - Psychosocial stress and urinary cortisol excretion in marmoset monkeys
      (Callithrix kuhli).
AB  - Activation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the
      hallmarks of the physiological responses to psychosocial stressors. The most
      common method of assessing HPA function is via the measurement of plasma cortisol
      levels. However, venipuncture involves capture and restraint, which can modify
      HPA function. We validated a noninvasive procedure for monitoring HPA responses
      to stressors by measuring excretion of free urinary cortisol. Samples collected
      throughout the day displayed marked circadian variation, with low cortisol values
      in first-void samples, followed by a mid-morning peak in cortisol excretion.
      Concentrations of excreted cortisol declined throughout the day. Exposing
      marmosets to mild and moderate stressors (11 h isolation in a small cage and
      manual restraint) increased excreted cortisol concentrations in a dose-dependent
      fashion: isolation in a small cage led to elevated cortisol in afternoon samples,
      while manual restraint and isolation produced elevated cortisol in both morning
      and afternoon samples. The marmoset HPA is differentially sensitive to rather
      subtle variations in stressors, and these results show that urinary cortisol
      excretion is a valid and sensitive index of the HPA response to these stressors.

PMID- 9251963
TI  - Effects of intermittent tail shock or water avoidance on proximal colonic motor
      contractility in rats.
AB  - Changes in proximal colonic mechanical activity and defecation during exposure to
      three different types of experimental stressors were examined in rats chronically
      implanted with 2 force transducers on the proximal colon. To validate the
      integrity of the recording system, meal-induced changes in proximal colonic
      contractility were initially measured in all rats 1-2 days prior to stress
      induction. Different groups of ad lib fed rats were then exposed to tail shock,
      re-exposure to the shock chamber or water avoidance for 1 h over the next 1-2
      days. Two types of phasic colonic contractions, long (0-3/min) and short (6
      8/min) duration, were analyzed separately using a computer. Long duration
      contractions were significantly elevated 21-71% over fasting basal values from 61
      120 min following a meal. No other consistent changes during the prandial or
      postprandial period were observed. Tail shock significantly suppressed proximal
      colonic contractility from pre-shock values and increased fecal output and fluid
      content when compared to ad lib fed rats that were not shocked. Fecal output
      increased but proximal colonic contractility did not change when previously
      shocked rats were re-exposed to the tail shock chamber but not shocked. In rats
      exposed to water avoidance, proximal colonic contractility was minimally
      suppressed but defecation was significantly greater than home cage control
      animals. These results indicate that proximal colonic contractile activity is
      differentially altered by exposure to different environmental stressors and may
      be a contributing factor in stress-induced bowel dysfunction.

PMID- 9251964
TI  - Central ANG II receptor involved in carotid sinus reflex resetting in chronically
      stressed rats.
AB  - The performance of carotid sinus baroreceptor reflex (CSR) was characterized in
      chronically stressed rats by changing intracarotid sinus pressure (ISP) and
      constructing ISP-MAP (mean arterial pressure) relationship curve. The role of
      central angiotensin II (ANG II) receptors in the changes of CSR performance
      induced by chronic stress was determined. Rats were subjected to foot-shock
      stress for two weeks. The carotid sinus was isolated from the systemic
      circulation and the ISP changed in a stepwise manner. The results showed that in
      chronically stressed rats, ISP-MAP relationship curve shifted upward, the set
      point was significantly higher than that obtained from the unstressed group, and
      the reflex gain and the MAP range were significantly smaller than those in
      unstressed rats. After intracerebroventricular injection of saralasin (20 ng),
      MAP range was augmented and the set point decreased significantly. Injection of
      vehicle did not lead any significant differences between the parameters of the
      reflex measured before or after injection in either the stressed or the
      unstressed rats. Furthermore, administration of ANG II (10 microg) induced a
      significant increase in the set point and decrease in the reflex gain in the
      unstressed rats. The responses of CSR to ANG II were completely blocked by
      pretreatment of saralasin. These findings suggest that chronic stress could
      induce the decreased CSR function in the normotensives and central ANG II
      receptors involved in the resetting of CSR in the chronically stressed rats.

PMID- 9251965
TI  - Are physiological changes in meal-fed rats determined by the amount of food
      ingested in the last meal or due to feeding schedule?
AB  - Rats trained to eat a single meal from 0800 to 1000 AM, (MF rats), increased food
      intake from the 1st (7.0 g) to the 13th (16.1 g) day and showed higher hepatic
      glycogen concentration and glycemia during fasting. To verify if these changes
      were determined by the higher food intake or due to the disciplining condition we
      compared rats at the 1st (MF(1st day-5 g) group) and 13th day (MF(13th day-5 g)
      group) of training, refed with a fixed amount of food (5 g). In addition, a third
      group (MF(13th day-12 g) group) composed by trained meal-fed rats, refed on day
      13 with approximately 75% of food ingested by MF rats on day 13 ( 12 g) of
      feeding training was included. The experiments with these 3 groups were performed
      at zero (1000 h), 6 (1600 h), 13 (2300 h), 18 (0400 h) and 22 (0800 h) h after
      meal. Our results demonstrated that part of the physiological changes of MF rats
      is consequence of feeding training (increased food intake during the fixed meal
      time and spontaneous elevation of glycemia 13 h after meal) and part of the
      differences (hepatic glycogen concentration, gastric and intestinal emptying)
      correlate well with effective time of fasting. In addition, hepatic
      gluconeogenesis from L-lactate and glycerol was influenced by both factors.

PMID- 9251966
TI  - Exposure to sweetened solutions enhances the anorectic effect of naloxone but not
      d-fenfluramine.
AB  - The effects of prolonged exposure of rats to sweetened caloric (sucrose) and non
      caloric (saccharin) solutions on subsequent sensitivity to the anorectic effects
      of naloxone and d-fenfluramine were investigated in a series of experiments. In
      Experiment 1, rats given 18 days exposure to 10% sucrose showed greater
      sensitivity to the anorectic effects of naloxone (0.125-1.0 mg/kg, IP) in a
      separate feeding test, than did controls or rats exposed to 0.2% saccharin. This
      effect was replicated in Experiment 2, and here rats exposed to a palatable
      quinine-sucrose solution that was less preferred than saccharin also showed an
      enhanced sensitivity to naloxone, similar to that seen in the group exposed to
      sucrose alone. In Experiment 3, prior exposure to sucrose, quinine-sucrose or
      saccharin had no effect on the anorectic effects of dexfenfluramine (1.0 and 2.0
      mg/kg), while the effect of naloxone (1.0 mg/kg SC) was enhanced by exposure to
      the two sucrose solutions. All sucrose-exposed rats gained more weight than did
      control or saccharin-exposed rats. These data suggest that the consumption of
      palatable calorie-containing solutions selectively alters sensitivity to
      naloxone, and a number of possible explanations are discussed.

PMID- 9251967
TI  - Nutritional effects on operant visual learning in Drosophila melanogaster.
AB  - The nutritional effects on operant visual learning behavior were investigated in
      a flight simulator. Operant visual learning and memory formation were normal in
      Drosophila (S-flies) reared on standard medium, but absent in flies (P-flies)
      raised on Peking medium. S- and P-flies were transferred to the alternative
      medium soon after hatching and their progeny was also raised on corresponding
      medium for several generations. respectively. S-flies transferred showed
      significantly reduced learning acquisition and 20 min memory retention, and
      operant visual learning along with memory formation was abolished in their
      progeny within three generations. Transferred P-flies recovered slowly their
      learning acquisition and memory formation to normal levels within five
      generations. Further studies suggested that low protein and minerals or high
      carbohydrate contents in Peking medium might be related to abnormal performance
      of P-flies. These results confirm the feasibility of affecting learning behavior
      by dietary regimens and developing an insect model of maternal malnutrition for
      pre- or post-natal malnutrition in Drosophila.

PMID- 9251968
TI  - Feeding behaviour and food utilisation in tilapia, Oreochromis niloticus: effect
      of sex ratio and relationship with the endocrine status.
AB  - The feeding behaviour of male monosex, female monosex, and mixed groups of
      Oreochromis niloticus was studied under conditions of self-feeding. Feeding
      activity was observed almost exclusively during the light period. The food intake
      pattern was similar whatever the sex ratio, and voluntary food intake (VFI)
      appeared lower in the male monosex groups than in the others. Male monosex groups
      displayed higher specific growth rates (SGR) and a lower food conversion ratio
      than female monosex and mixed groups. The SGR of males was higher in the monosex
      than in the mixed groups, whereas females of mixed and monosex groups displayed
      no significant difference in SGR. The efficiency of food utilisation was also
      analysed: nutrient retention ratios were higher in male monosex than in female
      monosex and mixed groups. Males displayed a distinctly higher metabolic capacity.
      Differences in sex-related hormones (11 ketotestosterone = 11-KT, 17beta
      Oestradiol = 17beta-E2) and a metabolic hormone (triiodothyronine = T3) were
      observed between males and females. The hypothesis of an involvement of these
      hormones in the higher metabolic capacity of males is discussed. The observed
      differences in feeding behaviour between the different groups also suggest an
      effect of social interactions on the efficiency of food conversion and thus on
      the differential growth of males and females.

PMID- 9251969
TI  - The effects of isolation-rearing of rats on behavioural responses to food and
      environmental novelty.
AB  - Isolation-reared rats exhibited enhanced behavioural responses to novelty, but
      only some aspects of such behavior was affected. In Experiment 1, environmental
      neophobia was enhanced but food neophobia was diminished in isolation-reared rats
      compared to socially reared rats. However, in Experiment 2, when subjects were
      not handled extensively prior to testing, no differences in behavioural responses
      to environmental or food novelty in an open-field were observed between rearing
      groups. The difference between these experiments was hypothesized to be the
      result of ceiling effects produced by increased anxiety or arousal in experiment
      2 in which the animals had not been extensively handled. In summary, in these
      experiments anticipatory responses to novelty were alterred by isolation-rearing
      but the behavioural expression of this increased sensitivity was determined by
      intrinsic aversive/rewarding or arousing qualities of novel environments and
      novel foods.

PMID- 9251970
TI  - The effects of isolation-rearing on sucrose consumption in rats.
AB  - Three experiments examined the hypothesis that social isolation of weanling rats
      potentiates hedonic processes by examining the consumption of sucrose solutions.
      In the first experiment no differences in consumption were found between socially
      reared rats and isolation-reared rats allowed to consume sucrose in a familiar
      test apparatus. In a second experiment socially-reared rats and isolation-reared
      rats were food and water deprived. Again, no differences in consumption were
      found. In a third experiment socially reared and isolation-reared rats were
      allowed to consume sucrose presented in either an ascending or descending order
      of concentration. When given sucrose in an ascending order of presentation
      isolation-reared rats consumed significantly more sucrose than socially reared
      rats. This suggests that isolation-rearing increased the effects of positive
      contrast, and is consistent with other observations of increased incentive
      motivation in isolates.

PMID- 9251971
TI  - The effects of isolation-rearing on preference by rats for a novel environment.
AB  - In the previous paper isolation-reared rats exhibited enhanced environmental
      neophobia under some conditions in an open-field. However, previous work has
      shown that isolation-reared rats have greater preferences for a novel environment
      in a dimly lit enclosed box. The hypothesis examined in the present experiments
      was that manipulation of the intrinsic aversive qualities of such an environment,
      by altering lighting conditions, could reverse the preference which isolation
      reared rats exhibit for a novel chamber. When preference for a novel chamber was
      examined in a non-aversive environment in Experiment 1, isolation-reared rats
      exhibited a preference for a novel environment which was enhanced compared to
      social controls. When tested under more aversive white light conditions in
      Experiment 2, no differences in novelty preference were observed between
      isolation-reared and socially reared rats. Thus, the increased sensitivity to
      novel environments by isolation-reared rats appears to be critically dependent on
      the arousing or aversive properties of the testing conditions.

PMID- 9251972
TI  - N-methyl-DL-aspartic acid lesions of the medial preoptic area disrupt ongoing
      parental behavior in male rats.
AB  - The effects of axon-sparing, neurotoxic lesions of the medial preoptic area
      (MPOA) with N-methyl-DL-aspartic acid (NMA) on previously established parental
      behavior in male rats were investigated. Adult, sexually-inexperienced male rats
      were gonadectomized and seven days later implanted sc with a single estradiol
      (E2)-filled Silastic capsule on treatment Day 1. Three progesterone (P4) capsules
      were implanted sc on treatment Day 3 and removed on Day 21, one day prior to the
      start of behavioral testing. Males were tested daily with foster pups in order to
      induce parental behavior, i.e., contacting the test pups, pup retrieval,
      grouping, and crouching over three foster pups. Full parental behavior appeared
      in these males after an average of 3 days. After testing on the third consecutive
      day of parental behavior, parental males were infused bilaterally with either NMA
      or vehicle into the MPOA. NMA infusions resulted in a significant decline in all
      components of parental behavior by the next test session, a deficit which
      persisted throughout the 5 days of post-infusion testing. In contrast, parental
      care continued to be displayed in animals given vehicle infusions. These findings
      demonstrate that the cells in the MPOA play an important role in regulating
      ongoing parental care in male rats and indicate that the neural substrates
      controlling parental behavior in male and female rats are similar.

PMID- 9251973
TI  - Ventromedial hypothalamus lesions increase the dipsogenic responses and reduce
      the pressor responses to median preoptic area activation.
AB  - In this study, we investigated the participation of adrenergic receptors of the
      median preoptic area (MnPO) and the participation of ventromedial hypothalamus
      (VMH) in angiotensin II-(ANG II)-induced water intake and pressor responses. Male
      rats with sham or electrolytic VMH lesions and a stainless steel cannula
      implanted into the MnPO were used. Noradrenaline, clonidine (an alpha2-adrenergic
      receptor agonist), or phenylephrine (an alpha1-adrenergic receptor agonist)
      injected into the MnPO of sham-lesioned rats reduced water ingestion induced by
      ANG II injected into the same area. In VMH-lesioned rats ANG II-induced water
      intake increased with a previous injection of noradrenaline, phenylephrine, or
      isoproterenol. The pressor response induced by ANG II injected into the MnPO was
      reduced in VMH-lesioned rats, whereas the pressor response induced by clonidine
      was abolished. Previous treatment with noradrenaline and phenylephrine into the
      MnPO of sham-lesioned rats produced a pressor response, and a hypotensive
      response was obtained with the previous administration of noradrenaline,
      phenylephrine or isoproterenol into the MnPO of VMH-lesioned rats. These results
      show that VMH is essential for the dipsogenic and pressor responses induced by
      adrenergic and angiotensinergic activation of the MnPO in rats.

PMID- 9251974
TI  - Differential response to intraoral sucrose, quinine and corn oil in crying human
      newborns.
AB  - Intraoral sucrose induces rapid and sustained calm in crying newborns and
      transiently increases mouthing and hand-mouth contact. To determine whether these
      effects are specific to sucrose and to explore which properties of orogustatory
      stimuli might contribute to this effect, 60 crying newborns were randomized to
      receive 250 ul of 24% sucrose solution, 0.25% quinine hydrochloride solution, or
      corn oil as well as water in a mixed parallel crossover design. Relative to
      water, sucrose persistently reduced crying, and transiently increased mouthing
      and hand-mouth contact as previously demonstrated. While quinine produces a
      "disgust" face in calm infants, in crying infants it transiently decreased crying
      and increased mouthing, but did not affect hand-mouth contact. Corn oil had no
      specific effect on crying, mouthing or hand-mouth contact. The results imply that
      crying newborns respond differentially to orogustatory stimuli, that taste
      "salience" rather than positive hedonic valence may account for initial crying
      reduction and increased mouthing, and that these behavioral effects are not
      induced by at least one lipid nutrient.

PMID- 9251975
TI  - Elevated blood copper/zinc ratios in assaultive young males.
AB  - In research conducted over the past 20 years, we have observed abnormal trace
      metal concentrations, including elevated serum copper and depressed plasma zinc,
      in blood samples collected from violence-prone individuals. The purpose of the
      study reported here was to test the validity of our observation that assaultive
      young males have elevated blood copper/zinc (Cu/Zn) ratios when compared to a
      control group of young males with no history of assaultive behavior. All male
      patients between the ages of 3 years and 20 years who made a first visit to the
      outpatient Pfeiffer Treatment Center in Naperville, Ill., during a two-month
      period were evaluated. Based on interviews with patients and their families and
      application of a standardized behavior scale, 135 assaultive young males and 18
      controls with no history of assaultive behavior were identified. Blood samples
      were collected from test subjects and controls and analyzed for serum copper and
      plasma zinc concentrations by an independent laboratory using atomic absorption
      methods. The median Cu/Zn ratio for the assaultive subjects was 1.40 compared to
      1.02 for controls, a statistically significant difference (t = 5.94; p < 0.01).

PMID- 9251976
TI  - Circadian rhythm of temperature selection in a nocturnal lizard.
AB  - We recorded body temperature and locomotor activity of Tokay geckos (Gekko gecko)
      with free access to a heat source under a 14:10 light-dark cycle and in constant
      darkness. Under the light-dark cycle, the lizards selected higher temperatures
      during the light phase, when locomotor activity was less intense. Rhythmicity in
      temperature selection was transiently disrupted but later resumed when the
      animals were placed in constant darkness. These results demonstrate the existence
      of a circadian rhythm of temperature selection in nocturnal ectotherms and extend
      previous findings of a temporal mismatch between the rhythms of locomotor
      activity and temperature selection in nocturnal rodents.

PMID- 9251977
TI  - Genetic study of behavioral and pituitary-adrenocortical reactivity in response
      to an environmental challenge in pigs.
AB  - The adaptive response to environmental challenges involves both behavioral and
      neuroendocrine adjustments, and genetic factors have been shown to partly
      determine the intra- and interspecific variability observed in stress responses.
      To gain access to the biological and genetic basis of this variability,
      differences in neuroendocrine and behavioral responses to a 10-min novel
      environment exposure were studied in Meishan (MS) and Large White (LW) pig
      breeds, as well as in their F1 (MS x LW), F1R (LW x MS), and F2 (F1 x F1)
      crossings. Different behavioral scores were recorded and blood was taken by
      venipuncture, before and after the test, to measure levels of stress hormones
      (adrenocorticotropic hormone: ACTH and cortisol). MS pigs exhibited low
      vocalization, locomotion, and defecation scores when compared to LW. F1s showed
      intermediate locomotion scores. The vocalization scores of F1s were not
      significantly different from the respective scores of their parental MS and LW
      breeds. The defecation scores in F1s showed that there was some degree of
      dominance in the MS direction. Basal and poststress cortisol levels were higher
      in MS, F1s, and F2 than in LW, suggesting the dominance of this trait. Basal ACTH
      levels did not differ between the genetic types, whereas LW displayed higher
      poststress ACTH levels than MS. Phenotypic correlations were analyzed in the F2
      segregating cross to study a possible link between behavioral and neuroendocrine
      traits. All behavioral variables were intercorrelated with 3 levels of
      association. The correlations between vocalization and locomotion scores and
      poststress ACTH levels suggest that these measures reflect the level of
      reactivity to the environmental challenge, and that they may share a common
      genetic control.

PMID- 9251978
TI  - Effects of central oxytocin administration on intraoral intake of glucose in
      deprived and nondeprived rats.
AB  - We evaluated the effects of lateral intracerebroventricular administration of
      oxytocin (OT) and/or a selective oxytocin-receptor antagonist (OTX), 1-deamino-2
      D-Tyr-(OEt)-4-Thr-8-Orn-OT, on ingestion of intraorally delivered 12.5% glucose
      in rats that were either nondeprived or deprived of food for 20 h. In deprived
      rats, OT delivered 30 min before an initial intake test yielded a dose-related
      reduction of intraoral glucose intake. The highest dose tested, 20 nmol, reduced
      intraoral glucose intake by 45%. The effect was short-lived, however. Intraoral
      intake for a second test, initiated 60 min after the termination of the first,
      increased as a function of OT dose so that total session intake was unaffected by
      OT treatment. The suppression of intraoral intake by 20 nmol OT was reversed by
      pretreatment (45 min before testing) with OTX. In nondeprived rats, by contrast,
      OT yielded no effect on first-test, second-test, or total session intakes.
      Significant increases in first-test and total session intakes were obtained when
      OTX (20 nmol) was administered alone both in deprived (32% increase in first-test
      intake) and nondeprived (31% increase) rats. In general, the results obtained are
      consistent with the suggestion that OT contributes to the control of meal size
      and, in particular, to the process of satiation, which is the aspect of ingestive
      control highlighted by the specialized intake test used in the present study.

PMID- 9251979
TI  - Model for voluntary wine and alcohol consumption in rats.
AB  - It has been suggested that moderate consumption of ethanol and wine has a
      protective effect on human health. Animal models used to date for alcohol
      consumption can not mimic real situations in humans because the consumption is
      forced and/or excessive. The present study proposes to determine the effects of a
      voluntary and ad lib consumption model more similar to that of human behavior.
      Male Wistar rats had free access to either standard diet and water or the same
      diet plus red wine, sweet wine, or a solution equivalent to red wine (13.5%
      ethanol) or to sweet wine (20% ethanol + 130 g/L sucrose) for 30 days or 6
      months. Daily wine consumption was 15.8 +/- 0.9 and 2.0 +/- 0.2 ml/day for sweet
      and red wines, respectively. The consumption of each of the alcoholic solutions
      was similar to that of the wine they were simulating. Drinking wine or ethanol
      did not affect food and water intakes or growth rate. Plasma metabolites were not
      substantially affected by consumption of wine or ethanol. Although moderate and
      high wine consumption did not change the activity of plasma marker enzymes of
      tissue damage, the consumption of the 2 alcoholic solutions caused a long-term
      increase in the activity of aspartate aminotransferase. It seems that wine
      consumption protects the organism from hepatic lesions induced by ethanol alone.

PMID- 9251980
TI  - Influence of olfactory stimulation on nociceptive behavior in mice.
AB  - The reactions elicited by nociceptive stimulations were studied in mice exposed
      to the presence of different odors: positive (attractive), negative (aversive),
      or neutral. In a first set of experiments, the animals were not habituated to the
      odors before the nociceptive stimuli were applied; in this case, the olfactory
      environment during experienced pain had essentially no effect on the nociceptive
      reactions, whatever the nature of the odors. In a second set of experiments, the
      animals were habituated to the same odor for 20 days. The control group consisted
      of mice habituated to and tested in the presence of the odor of the laboratory.
      In that case, compared to controls, the neutral odor had no influence on
      nociceptive reactions. By contrast, the positive odor decreased and the negative
      odor increased the reactions, especially when the intensity of the nociceptive
      stimulus was low. Moreover, it has been shown that the reactions elicited during
      a second nociceptive stimulation period depend on the perception of pain animals
      experience during the first stimulation, which depended, in turn, on the odor
      associated with it. Results are discussed in terms of opioid-mediated
      interactions between olfaction and pain.

PMID- 9251981
TI  - A new system analysis of motor and locomotor activities associated with a
      microdialysis study of pressure-induced dopamine increase in rats.
AB  - In this work, we report a new analysis system to quantify the behavioral
      disorders observed in the model of the rat submitted to high pressure and
      monitored by piezoelectric sensor. The major advance consists in a spectral 3D
      representation of LMA and tremor, which provides a better selectivity than
      previous systems. This behavioral processing indicated that tremor is
      characterized by a 7-14 Hz frequency band and LMA by a 20-35 Hz frequency band.
      The association of this system to the microdialysis technique to simultaneously
      evaluate the striatal DA level confirms that pressure-induced striatal DA
      increase is in great part linked to the LMA, and supports the concept of a
      complex ethiology for this symptom. We conclude that this new behavioral system
      analysis associated with microdialysis study constitutes a powerful tool to
      investigate the role of different neurotransmitters in the occurrence of the
      behavioral components described in the HPNS of rats.

PMID- 9251982
TI  - Influence of anterodorsal thalami nuclei on ACTH release under basal and
      stressful conditions.
AB  - Experiments were carried out to evaluate the effect of anterodorsal thalami
      nuclei (ADTN) lesions on plasma ACTH and corticosterone (C), in unstressed and
      stressed rats. Thirty days after lesion, basal values of plasma ACTH, plasma and
      adrenal C were significantly higher than those in sham lesioned rats (p < 0.05: p
      < 0.05; p < 0.01, respectively). Chronic stress (forced immobilization, 15
      min/day, during 12 days) in sham-operated animals produced a significat increase
      in ACTH (p < 0.05) and plasma C (p < 0.05), and a slight decrease in adrenal C,
      as compared to unstressed rats. In lesioned stressed rats, plasma ACTH was below
      that found in unstressed lesioned and in sham-lesioned stressed rats (p < 0.05).
      Variations of plasma C concentrations of stressed lesioned rats were not
      significant. The adrenal glands of stressed lesioned rats showed a significantly
      lower content of C than that in unstressed lesioned rats (p < 0.005). It is
      concluded that ADTN in rats may play a significant role in regulating the
      hipophyso-adrenal system.

PMID- 9251983
TI  - Effect of chronic treatment with propranolol on the cardiovascular responses to
      chronic cold exposure.
AB  - The purpose of this study was to determine whether beta-adrenergic receptors are
      involved in the elevation of blood pressure, tachycardia, and cardiac hypertrophy
      in rats chronically exposed to cold (5 degrees C). Four groups of rats were used.
      Two groups of rats were exposed to 5 degrees C and the other 2 groups were kept
      at 25 degrees C. In each temperature condition, one group received regular food
      while the other received food to which a nonspecific beta-adrenoceptor
      antagonist, d,l-propranolol, was added. The blood pressure of the untreated, cold
      exposed group increased significantly within 3 weeks of exposure to cold and
      remained elevated until the end of the experiment. Chronic treatment with d,l
      propranolol decreased the rate of cold-induced elevation of blood pressure at
      doses of 1.0 and 1.2 g/kg of food, and produced a complete reversal of
      hypertension at a higher dose ( 1.5 g/kg of food). Propranolol also prevented
      tachycardia in cold-exposed rats. The fact that propranolol decreased the
      elevation of blood pressure and prevented tachycardia suggests that both beta1-
      and beta2-adrenoceptors are blocked in cold-exposed rats. Propranolol, however,
      did not affect cold-induced cardiac hypertrophy.

PMID- 9251985
TI  - The influence of low blood pressure and baroreceptor activity on pain responses.
AB  - The influence of baroreceptor modulation on pain perception has been extensively
      studied in normal and hypertensive subjects, but not in hypotensive subjects. The
      present experiment was performed to verify the following hypotheses: 1.
      Hypotensive subjects exhibit an increased pain response following baroreceptor
      activation compared to normals; 2. unlike the hypotensives, normal subjects, with
      normal baroreceptor reflexes, would learn to choose more often the baroreceptor
      activation condition compared to the opposite condition, during painful
      stimulation; 3. sensory and pain thresholds are correlated with blood pressure.
      The subjects (39 men), divided according to low and normal blood-pressure groups,
      participated in an experiment in which electrically-induced pain ratings and pain
      evoked potentials were measured. Baroreceptor manipulation was performed by means
      of the PRES procedure. Whereas hypotensive subjects did not perceive any pain
      difference between the two baroreceptor conditions, activation and inhibition,
      normotensive men were able to perceive the baroreceptor activation condition as
      less painful. Similarly to subjective ratings, pain-evoked potentials of the low
      blood-pressure group showed a reversed trend compared to normals: larger
      somatosensory evoked potentials (N150-P260) to the baroreceptor activation
      condition and the opposite to the baroreceptor deactivation condition.
      Furthermore, results showed a negative correlation between diastolic blood
      pressure and sensory perception threshold, and a positive correlation between
      systolic pressure and pain threshold. Contrary to expectations, the rate of
      choice of baroreceptor conditions during painful stimulation did not show, in
      either group, any preference for baroreceptor activation.

PMID- 9251984
TI  - Cholecystokinin receptors do not mediate the behavioral effects of
      lipopolysaccharide in mice.
AB  - To test the possible role of cholecystokinin (CCK) in the decrease of social
      exploration induced by intraperitoneal (IP) injection of lipopolysaccharide (LPS,
      100 microg/kg), mice were pretreated with IP or intracerebroventricular (ICV)
      injection of the CCKA receptor antagonist L-364,718 (3 mg/kg and 10 microg/kg,
      respectively) and the CCKB receptor antagonist L-365,260 (1 mg/kg and 10
      microg/kg, respectively). L-364,718 and L-365,260 did not alter LPS-induced
      decrease in social investigation, whatever the route of administration,
      suggesting that endogenous cholecystokinin does not mediate the effect of
      proinflammatory cytokines on social exploration in mice.

PMID- 9251986
TI  - Removal of the submaxillary salivary glands and infection with the trematode
      Schistosoma mansoni alters exploratory behavior and pain thresholds in female
      mice.
AB  - In this study, CD-1 female mice, deprived of the submaxillary salivary glands,
      were infected with S. mansoni and their behavior was observed 15 weeks after
      infection, when the eggs of the parasite are present in the brain. Sialectomized
      infected mice showed changes in exploratory activity, sniffing, and wall-rearing
      in the open-field and in the black/white box, but no differences in pain
      sensitivity were observed on the hot plate. The present results suggest that the
      modifications in the behavior of sialectomized infected mice might be associated
      with the inability of the animals to cope with the aversive effects of the
      infection and, most probably, with modifications in the levels of polypeptides
      released into the bloodstream by the salivary glands, affecting the NGF
      responsive cells of the nervous, endocrine, and immune systems.

PMID- 9251987
TI  - Temporal segregation in coexisting spiny mice (genus Acomys): role of photoperiod
      and heterospecific odor.
AB  - Daily rhythms of activity and body temperature were measured in golden spiny mice
      Acomys russatus, acclimated for 2 weeks, at least, to 2 different photoperiod
      regimes (16L:8D; 8L:16D) at a constant ambient temperature of 28 degrees C. For
      recording body temperature, VM-FM (Mini-Mitter Co. Inc., Sunriver, OR)
      transmitters were implanted. For activity measurements, an infrared sensor
      (Hengstar BL 68 907F, Japan, using a Lodestar PS-303 power supply, Taiwan)
      mounted on each cage. Both rhythms were also measured in the same individuals
      exposed to chemical signals released in the urine of A. cahirinus. The results of
      this study show that both rhythms of A. russatus correlate and respond to changes
      in photoperiod regimens, as well as to the chemical signals. However, the
      correlation changes under the 2 photoperiod regimens. Under LD acclimation, a
      decrease in the correlation is noted, as a response to the addition of chemical
      signals. Our results suggest that the different responses due to the different
      light regimens represent 2 seasons in nature, where presumably each season
      demands a different physiological response.

PMID- 9251988
TI  - The stress of not being able to perform dustbathing in laying hens.
AB  - The stress of not being able to perform dustbathing was studied in small groups
      of laying hens. The birds were reared and kept for 2.5 years in cages with either
      sand ("sand birds") or wire floors ("wire birds"), and subsequently deprived of
      sand (sand birds) or given access to sand (wire birds). Before this change, wire
      birds had a higher incidence of unilateral wing/leg stretching and stereotypic
      pecking compared to sand birds; however, there was no difference in
      corticosterone concentrations. Deprivation of sand in the sand birds resulted in
      a total absence of dustbathing and in a significant increase in corticosterone
      concentrations. Although the wire birds dustbathed on the wire before the change
      of floors, there was a significant increase in the incidence of dustbathing after
      sand was provided, but no changes in the concentrations of corticosterone.
      Threats and allopecks decreased in the wire birds after access to sand, whereas
      no changes were found in the sand birds. Stereotypic pecks on feathers were
      absent in the sand birds, but were frequent in most of the wire birds both before
      and after they were given sand. Also, in the wire birds, all feather pecking
      (stereotypic and nonstereotypic) was positively correlated with the concentration
      of corticosterone, and this kind of pecking may, thus, be an expression of stress
      in laying hens. We conclude that the nonperformance of dustbathing behavior is
      associated with the experience of stress.

PMID- 9251989
TI  - Diurnal variation in the effect of chronic mild stress on sucrose intake and
      preference.
AB  - Diurnal variation (depression worse in the morning) is one of the diagnostic
      criteria for the melancholic subtype of major depression. This study examined
      diurnal variation in the effects of chronic mild stress (CMS), an animal model of
      depression, by testing Wistar rats at different phases of the light-dark cycle.
      CMS decreased sucrose intake and sucrose preference in animals tested at the
      start of the dark phase (the most active period in this nocturnal species), but
      not in animals tested during the light phase. CMS also decreased body weight in
      both groups; however, the effects of CMS on sucrose intake in the dark phase were
      not secondary to body weight changes. On the contrary, loss of body weight led to
      underestimates in the magnitude of the effects of CMS on sucrose intake. The
      results support the validity of the CMS procedure as a model of melancholia. The
      discussion addresses criticisms of this position that have been raised in two
      recent publications.

PMID- 9251990
TI  - A simple design for a small fixed four-electrode brain stimulation array.
AB  - Anatomical studies of intracranial self-stimulation (ICSS) reward in rats often
      use the lesion method and, therefore, require repeated behavioral testing before
      and after the lesion. Other anatomical studies on unlesioned rats use a moveable
      electrode to permit testing at a number of ICSS sites. Combining these methods
      would yield still more information, but repeated testing is not possible due to
      the damage created by lowering the electrode. To meet this need, an array of 4
      fixed vertically-spaced electrodes was devised. Electrodes are constructed from
      strands of 0.14-mm (0.0045'') Teflon-insulated stainless-steel wire, 4 of which
      are glued into an implantable bundle. A 4-channel IC rotary switch is implanted
      on the rat's head to permit the use of an inexpensive 2-channel electrode lead
      and commutator. In our laboratory, electrodes were vertically spaced at 0.3 mm,
      spanning the dorsoventral extent of the lateral hypothalamus and yielded stable
      rate-frequency curves over the usual 3-4 month period of behavioral testing.

PMID- 9251991
TI  - The influence of menstrual-cycle phase on the relationship between testosterone
      and aggression.
AB  - Plasma testosterone levels and aggressive behavior were measured in 12 women with
      and without perimenstrual affective symptomatology (e.g., depression,
      irritability) during the menstrual, midfollicular, ovulatory, and premenstrual
      phases of the menstrual cycle. The Point Subtraction Aggression Paradigm was used
      to quantify aggressive response to provocation. Subjects had two response
      options: a point-maintained option (100 presses earned a point worth 10 cents)
      and an aggressive response option (10 presses ostensibly subtracted a point from
      a fictitious partner's counter). Subjects were provoked by the periodic
      subtraction of a point that was attributed to the responding of a fictitious
      opponent. Although plasma testosterone levels (determined by radioimmunoassay)
      increased significantly during the ovulatory phase, aggressive response to
      provocation remained unchanged across the menstrual cycle. Plasma testosterone
      did not differ between the 2 groups during any phase. A relationship between
      plasma testosterone levels and use of the aggressive response option was seen
      only during the midfollicular phase (Spearman r = .673, p = .017). These
      preliminary data suggest that: 1. The relationship in female subjects between
      endogenous testosterone and aggressive behavior is inconsistent; 2. self-report
      of perimenstrual symptomatology is a more consistent predictor of aggressive
      behavior across the menstrual cycle than plasma testosterone; and 3.
      perimenstrual emotional symptomatology is not related to testosterone levels.

PMID- 9251992
TI  - Selective activation of A-delta and C nociceptive afferents by different
      parameters of nociceptive heat stimulation: a tool for analysis of central
      mechanisms of pain.

PMID- 9251993
TI  - The enigma of potassium ion in the management of dentine hypersensitivity: is
      nitric oxide the elusive second messenger?
AB  - We report the development of a 'second-messenger' model in an attempt to re
      evaluate the role of K+ as a desensitising agent. Despite unequivocal validation
      of the effectiveness of potassium-based dentifrices in the management of dentine
      hypersensitivity, the mechanism(s) of action of K+ remains unclear. Although
      experimental paradigms of the Nernst equation demonstrate a direct inhibitory
      effect of K+ ion upon nerve conduction, in vivo considerable constraints can be
      argued to preclude this mechanism of action. Indeed, measurements of solution
      velocity within individual dentinal tubules obtained by scanning electrochemical
      microscopy indicate that outward movement of tubular fluid may represent a far
      greater barrier to the inward diffusion of K+ ions than previously estimated from
      measurements of hydraulic conductance across bulk dentine. Despite such probable
      limited penetration of dentine tubules, K+ ions may desensitise deeply-located
      nerve terminals through activation of a second-messenger transduction pathway
      that is capable of controlling the gain of K+-evoked effects which remain
      physically restricted to the more superficial aspects of the tubule. In addition
      to a direct effect upon transmembrane potential K+ can also indirectly attenuate
      neural activity through effects upon levels of the endogenously-synthesised free
      radical, nitric oxide (NO). Stimulation of the release of NO by K+ has been
      observed using a variety of cell preparations, which include endothelium, smooth
      muscle, adrenal medulla, hypothalamus and cerebellum. Importantly, a growing
      number of studies now report that an increase in the production of NO is
      associated with analgesia through a modulation of nociceptive input and a
      downregulation of sensitised nociceptors, most likely achieved through an
      increase in intraneural content of cGMP. The clinical role of a K+-evoked
      liberation of NO as a principal mechanism in the management of dentine
      hypersensitivity is supported by recent findings which include: (1) the
      localisation of NADPH-diaphorase activity and inducible nitric oxide synthase
      (iNOS) immunoreactivity within odontoblasts, their processes in dentine, and the
      subodontoblast layer of the pulp; (2) iNOS causes a sustained release of large
      (nanomolar) amounts of NO; (3) NO is freely diffusible and capable of displaying
      remarkably potent effector actions at distant target cells; (4) the actions of NO
      may be enhanced by endogenous carrier molecules such as S-nitrosothiols; (5) the
      synthesis of NO can be evoked by concentrations of K+ ion far less (i.e. <1 mM)
      than those required for direct inhibitory effects upon neural activity.

PMID- 9251994
TI  - Mechanisms of touch-evoked pain (allodynia): a new model.
AB  - In this paper we review the current neurophysiological models of touch-evoked
      pain and present a new proposal that addresses the mechanisms of allodynia. The
      new model is based on the notion that A-beta mechanoreceptors can gain access to
      nociceptive neurones by means of a presynaptic link, at central level, between
      low threshold mechanoreceptors and nociceptors. We propose that the excitation of
      nociceptors provoked by a peripheral injury activates the spinal interneurones
      that mediate primary afferent depolarization (PAD) between low threshold
      mechanoreceptors and nociceptors. As a consequence of the increased and
      persistent barrage driving these neurones their excitability is increased such
      that, when activated by low threshold mechanoreceptors from areas surrounding the
      injury site, they produce a very intense PAD in the nociceptive afferents which
      is capable of generating spike activity. This activation would be conducted
      antidromically in the form of dorsal root reflexes (DRRs) but would also be
      conducted forward activating the second order neurones normally driven by
      nociceptors. The sensory consequence of this mechanism is pain evoked by the
      activation of low threshold mechanoreceptors from an area surrounding an injury
      site (allodynia).

PMID- 9251995
TI  - Prevalence and source of pain in pediatric inpatients.
AB  - Our knowledge of the prevalence and sources of pain within hospital is limited.
      The present study is an epidemiological investigation of pain in a pediatric
      hospital. All children who were inpatients in a tertiary care hospital (excluding
      Neonatal ICU and psychiatry patients) and one parent per child were potential
      subjects. Interviews were conducted on three weekdays. Parent interviews were
      used for children less than 5 years of age (n = 102); child interviews were used
      for children age 5 years and older (n = 98). Subjects reported the intensity and
      source of the worst, usual and current pain during the past 24 h, and help
      received for pain. Medical and demographic variables and analgesics prescribed
      and administered were obtained from the medical record. Forty-nine percent of
      subjects reported clinically significant levels of worst pain. Twenty-one percent
      of subjects had clinically significant levels of usual pain. Causes of pain were
      variable and included disease, surgery, and intravenous lines (I.V.). Pain
      intensity was not significantly related to age, gender, patient type (medical,
      surgical), or diagnostic category. Children were given significantly less
      medication than was prescribed, regardless of their reported pain level. Nurses,
      mothers, and 'no-one' were frequently reported as helping with pain. Medications
      and nonpharmacological methods were reported as helpful in managing pain. Many
      children endure unacceptable levels of pain during hospitalization. Pain
      prevention and management must be more aggressive. Pain assessment should be
      approached with the same attention as vital signs. Improvements in analgesic
      prescription and administration practices and non-pharmacological pain control
      methods are needed.

PMID- 9251996
TI  - Noxious and innocuous cold discrimination in humans: evidence for separate
      afferent channels.
AB  - The present study evaluated the ability of humans to discriminate temperature
      decreases in the noxious and innocuous cold range. Two groups of five subjects
      detected changes in cold stimuli applied to the maxillary face. For five
      subjects, adapting temperatures of 22 degrees, 16 degrees, 6 degrees and 0
      degrees C were used, and thresholds for detecting temperature decreases were
      determined using an adaptive psychophysical paradigm. Visual analogue scale (VAS)
      ratings of cold and pain sensation were also recorded at 5-min intervals
      throughout each session. A second group of five subjects performed a similar
      detection task, but in this case using classical psychophysical techniques
      (method of constant stimuli) and adapting temperatures of 22 degrees, 16 degrees,
      10 degrees and 6 degrees C. These subjects described the quality of the detected
      change in sensation, in addition to rating overall cold and pain sensation
      throughout the session. Detection thresholds were 0.27 degrees, 0.48 degrees, 4.8
      degrees, 8.0 degrees and >10.0 degrees C for baselines of 22 degrees, 16 degrees,
      10 degrees, 6 degrees and 0 degrees C, respectively, indicating that
      discrimination was better in the innocuous cool (22 degrees and 16 degrees C)
      than in the noxious and near-noxious cold (10-0 degrees C) range (P < 0.05).
      Tonic adapting temperatures of 22 degrees and 16 degrees C were always rated as
      cool but not painful, whereas adapting temperatures of 10 degrees and 6 degrees
      were sometimes and 0 degrees C usually rated as painful. Phasic temperature
      decreases from 22 degrees and 16 degrees C always produced cooling sensations,
      whereas decreases from baselines of 10 degrees and 6 degrees C produced primarily
      sensations of painful and non-painful prickle. These data suggest that different
      afferent channels mediate cool and noxious cold perception and add support to the
      hypothesis that noxious cold sensation is mediated by subdermal nociceptors.

PMID- 9251997
TI  - Coping strategies predict disability in patients with primary fibromyalgia.
AB  - We administered the Coping Strategies Questionnaire (CSQ) to 80 patients with
      fibromyalgia (FM) to determine the relationship between coping strategies and
      functional disability. A principal components factor analysis revealed two
      dimensions of patients' CSQ responses: Coping Attempts and Catastrophizing.
      Coping Attempts consists of five scales: Reinterpreting Pain, Ignoring Pain
      Sensations, Diverting Attention, Coping Self-Statements and Increasing Activity
      Level. Catastrophizing is comprised solely of the CSQ Catastrophizing scale. Both
      coping strategy dimensions were significantly related to patients' disability
      scores on the Sickness Impact Profile even after controlling for demographic and
      clinical variables as well as neuroticism. Coping Attempts was associated with
      higher levels of Physical (P < 0.05) and Total Disability (P < 0.01), and lower
      levels of Psychosocial Disability (P < 0.05). Catastrophizing was associated with
      higher levels of Total Disability (P < 0.01). These relationships suggest that
      investigators should attempt to identify Coping Attempts strategies that best
      reduce patients' psychological distress in the laboratory. It then may be
      possible to teach patients to use these strategies to reduce distress in their
      home and work environments.

PMID- 9251998
TI  - 'Booboos': the study of everyday pain among young children.
AB  - Three- to 7-year olds were observed in their day cares to determine the
      prevalence and nature of incidents of everyday pain (e.g. bumps, cuts, and
      scrapes). An observational checklist was used to record information on the
      behavioral responses of child and caregiver. The checklist showed excellent
      interrater reliability and supported the validity of the pain measure used. No
      age or sex differences in the incidence or severity of everyday pain were found.
      However, girls engaged more often in distress responses and received more
      physical comfort from adult caregivers. It was concluded that girls have a vocal
      response style which elicits responses from adult caregivers. No significant
      effect of age was found on intensity or duration of distress or on adult
      response, but frequency of help-seeking behaviors was found to decrease with age.
      Limited effects of age may be due to the age range restriction of 28-81 months.
      Analyses of temperment indicated that less adaptive children were more agitated
      prior to a pain incident. Analysis of behavioral context demonstrated that larger
      groups of children display a higher level of activity and individuals in the
      group display higher levels of agitation. Personal control of the child during a
      pain incident decreased within larger groups and increased with a high level of
      activity. Finally, it was found that children who experienced 'booboos' most
      often also responded to them most strongly, suggesting that increased exposure to
      this type of pain may lead to sensitization, rather than desensitization.

PMID- 9251999
TI  - Good patients cope with their pain: postoperative analgesia and nurses'
      perceptions of their patients' pain.
AB  - Patients routinely receive less analgesia postoperatively than they need.
      Previous attempts to understand this have examined the nurses' attitudes to
      analgesia and their ability to assess accurately the intensity of their patients'
      pain. The present study examined three hypotheses derived from an alternative
      view that undermedication results from patients failing to disclose their
      difficulty in coping with pain because this would lead to disapproval by nurses:
      (i) that analgesic intake is related, not to pain intensity but to patients'
      feelings of being unable to cope with pain and to nurses' assessment of their
      inability to cope; (ii) that nurses specifically underestimate patients' ability
      to cope with their pain; and (iii) that poor coping with pain is seen by nurses
      as indicative of a 'bad' patient. Pain ratings were completed by 56 patients
      undergoing minor abdominal surgery; nurses completed similar scales to show their
      perception of patients' pain, as well as a specially devised scale which measured
      how negatively or positively they felt about their patients. Nurses were
      sensitive to the intensity of their patients' pain, but underestimated how well
      patients felt they coped with pain and how much they wanted analgesia. Patients
      who experienced the worst pain, or whom the nurses perceived as coping least well
      with their pain, were evaluated by the nurses as unpopular and demanding.

PMID- 9252000
TI  - The initial effects of a cervical spine manipulative physiotherapy treatment on
      the pain and dysfunction of lateral epicondylalgia.
AB  - Manipulative therapy is frequently used in the management of musculoskeletal
      pain. A frequently reported clinical feature of this treatment is the immediacy
      with which it appears to initiate improvement in pain and function. A randomised,
      double blind, placebo controlled, repeated measures design was employed to study
      the initial effects of a cervical spine treatment technique in a group of 15
      patients with lateral epicondylalgia. Pressure pain threshold, pain-free grip
      strength, upper limb neurodynamics, pain and function were assessed prior to and
      following application of either a treatment, placebo or control condition. All
      subjects received all three conditions. Differences between the pre-post measures
      were used as indicators of change in subject's symptom profiles. The treatment
      condition produced significant improvement in pressure pain threshold, pain-free
      grip strength, neurodynamics and pain scores relative to placebo and control
      conditions (P < 0.05). In summary, this study demonstrates that manipulative
      therapy is capable of eliciting a rapid hypoalgesic effect.

PMID- 9252001
TI  - Transcutaneous nerve stimulation (TENS) during the first stage of labour: a
      randomized clinical trial.
AB  - Our objective was to study the efficacy of transcutaneous electrical nerve
      stimulation (TENS) in reducing pain during the first stage of labour. Using a
      prospective randomized placebo-controlled, double blind clinical trial, a patient
      controlled analgesia system was used to measure differences in outcome. Trials
      took place in a labour unit at the St. Antonius Hospital, Nieuwegein, The
      Netherlands, during a period of 18 months. Forty-six patients, during the first
      stage of labour, were treated with TENS, and 48 with a placebo apparatus. Main
      outcome measures were pain relief, amount of administered analgesics, obstetrical
      and neonatal outcome, and side effects. No significant differences occurred
      between groups in the number of requests for pethidine/promethazine. The foetal
      outcome in both groups was the same. TENS and placebo were considered equally
      effective by both patients and staff. In conclusion, TENS was not more effective
      than a placebo apparatus in relieving pain during the first stage of labour. No
      adverse side-effects occurred.

PMID- 9252002
TI  - Referred pain distribution of the cervical zygapophyseal joints and cervical
      dorsal rami.
AB  - The purpose of this study was to determine the distribution of referred pain from
      the cervical zygapophyseal joints (C0/1 to C7/Th1) and the cervical dorsal rami
      (C3 to C7). The subjects were 61 patients who had occipital, neck, and shoulder
      pain of suspected zygapophyseal origin in whom pain was reproduced by injection
      of contrast medium into the joints or by electrical stimulation of the dorsal
      rami. Under fluoroscopic control, the zygapophyseal joints from C0/1 to C7/Th1
      were stimulated by the injection of contrast medium and while electrical
      stimulation of the cervical zygapophyseal dorsal rami at segments C3 to C7 was
      performed during facet denervation. If injection or electrical stimulation
      reproduced the patient's usual pain, the distribution of referred pain was
      determined and the sites of referred pain were divided into 10 areas. A total of
      181 joints and 62 segments were studied. Each joint and dorsal ramus produced
      referred pain with a characteristic distribution. The main distribution of
      referred pain was as follows. Pain in the occipital region was referred from C2/3
      and C3, while pain in the upper posterolateral cervical region was referred from
      C0/1, C1/2, and C2/3. Pain in the upper posterior cervical region was referred
      from C2/3, C3/4, and C3, that in the middle posterior cervical region from C3/4,
      C4/5, and C4, and that in the lower posterior cervical region from C4/5, C5/6,
      C4, and C5. In addition, pain in the suprascapular region was referred from C4/5,
      C5/6, and C4, that in the superior angle of the scapula from C6/7, C6, and C7,
      and that in the mid-scapular region from C7/Th1 and C7.

PMID- 9252003
TI  - Involvement of increased excitatory amino acids and intracellular Ca2+
      concentration in the spinal dorsal horn in an animal model of neuropathic pain.
AB  - Neuropathic pain following nerve injury is believed to involve excitatory amino
      acids (EAAs) and Ca2+-mediated neuronal plastic changes in the central nervous
      system (CNS). This study was designed to investigate the changes in glutamate and
      aspartate contents in the dorsal half of the spinal cord following chronic
      constrictive injury (CCI) of the rat common sciatic nerve. We also examined the
      changes in intracellular calcium ion concentration ([Ca2+]i) of the spinal dorsal
      horn in transverse spinal slices in the same animal model. Thermal and mechanical
      hyperalgesia were observed on day 2 and thereafter following CCI (P < 0.0001). In
      the CCI rats to which 0.5 mg/kg of i.p. MK-801 was given 30 min prior to CCI and
      subsequently three daily treatments with 0.5 mg/kg of i.p. MK-801, the
      development of thermal and mechanical hyperalgesia was suppressed for a period of
      up to 7 days; however, hyperalgesia appeared on day 10 and day 14 (P < 0.001). In
      CCI rats, significant increases were observed in glutamate and aspartate contents
      on the ipsilateral side of the dorsal horn to nerve ligation on days 4, 7 and 14
      (P < 0.001). Moreover, significant increases in [Ca2+]i in the spinal dorsal horn
      were also observed in the superficial (lamina I-II) and deep layers (lamina V-VI)
      on the ipsilateral side to nerve ligation on days 4, 7 and 14 after nerve
      ligation in the spinal slices (P < 0.0001). The treatment with i.p. MK-801
      suppressed the increases in the contents of glutamate and aspartate and in
      [Ca2+]i on days 4 and 7. However, the ipsilateral contents of glutamate and
      aspartate significantly increased on day 14 (P < 0.001 and 0.003, respectively);
      the increased [Ca2+]i was also observed on day 14 (P < 0.001), and the spatial
      pattern of the increased regions was similar to untreated CCI rats. We interpret
      these results to indicate that neuropathic hyperalgesia induced by CCI in the rat
      is associated with an increase in glutamate and aspartate contents and the
      subsequent activation of NMDA receptors, followed by an increase in [Ca2+]i
      within dorsal horn of the spinal cord.

PMID- 9252004
TI  - Mechanical and thermal allodynia in chronic central pain following spinal cord
      injury.
AB  - Spinal cord injury (SCI) results in variable motor recoveries and chronic central
      pain syndromes develop in the majority of SCI patients. To provide a basis for
      further studies, we report a new rodent model of chronic central pain following
      spinal cord trauma. Male Sprague-Dawley rats (N = 10) were hemisectioned at T13
      and were tested both preoperatively and postoperatively and compared to sham
      operated controls (N = 10) for locomotor function, and mechanical and thermal
      thresholds of both paw withdrawal and supraspinal responses. Results support the
      development and persistence of allodynia which persists for 160 days. Locomotor
      function was tested using the Basso, Beattie and Bresnahan (BBB) open field test
      and only the limb ipsilateral to the hemisection was affected, demonstrating
      acute flaccid paralysis with motor recovery which approached normal values by
      postoperative day (POD) 15. Prior to the hemisection, the rats showed little to
      no paw withdrawal response to von Frey stimulation of 4.41 mN or 9.41 mN in both
      forelimbs and hindlimbs. Postoperatively, responses in both ipsilateral and
      contralateral forelimbs and hindlimbs increased over time and the increase was
      statistically significant compared to intra-animal presurgical and sham control
      values (P < 0.05). There were no significant side-to-side differences in limb
      responses preoperatively or beyond POD 15. The forelimbs and hindlimbs responded
      to von Frey hair strengths of 122 mN preoperatively and postoperatively with
      similar withdrawal frequencies that were not statistically significant.
      Preoperatively, the paw withdrawal latency to heat stimuli was 22.9 +/- 3.0 (mean
      +/- SE) and 20.1 +/- 3.1 sec for the hindlimbs and forelimbs, respectively.
      Postoperatively, the mean hindlimb and forelimb latency of paw withdrawals
      decreased to 11.9 +/- 1.8 and 9.2 +/- 2.5 sec, respectively. This decrease in
      thermal thresholds is statistically significant when compared to intra-animal
      preoperative and sham control values (P < 0.05). These data indicate that
      somatosensory thresholds for non-noxious mechanical and radiant heat which elicit
      paw withdrawal (flexor reflex) are significantly lowered following SCI. To
      further support the development and persistence of chronic pain following
      hemisection, supraspinal responses such as paw lick, head turns, attacking the
      stimulus, and vocalizations were elicited in response to mechanical and thermal
      stimuli and were statistically significant compared to presurgical intra-animal
      or sham control values (P < 0.05). Hemisected animals vocalized to von Frey hair
      bending forces of 49.8 with a mean of 6.0 +/- 1.2 times out of 10 stimuli
      compared to intra-animal presurgical and sham control values of zero. Supraspinal
      responses of hemisected animals to thermal stimuli occurred at lower temperatures
      that were statistically significant compared to sham control or preoperative
      values (P < 0.05). These chronic changes in thresholds to both mechanical and
      thermal stimuli represent the development and persistence of mechanical and
      thermal allodynia after SCI.

PMID- 9252005
TI  - High dose alfentanil pre-empts pain after abdominal hysterectomy.
AB  - This study tested the hypothesis that high dose systemic alfentanil administered
      before and during abdominal hysterectomy would pre-empt post-operative pain to a
      greater extent than administration of either low dose alfentanil or no alfentanil
      perioperatively. Patients (ASA 1 or 2) were randomly assigned to group 1 (n =
      15), no opioid; group 2 (n = 15), low dose alfentanil; or group 3 (n = 15), high
      dose alfentanil. Anaesthesia was induced in group 1 with midazolam and
      thiopentone and was maintained with isoflurane and 70% N2O in O2. Anaesthesia was
      induced in group 2 with midazolam, thiopentone and i.v. alfentanil (30 microg kg(
      1)), and was maintained with isoflurane, 70% N2O in O2, and bolus doses of i.v.
      alfentanil (10-20 microg kg(-1)) every hour. Anaesthesia was induced in group 3
      with midazolam and i.v. alfentanil (100 microg kg(-1)), and was maintained with
      70% N2O in O2, and an infusion of i.v. alfentanil (1-2 microg kg(-1) min(-1)).
      Blood samples were drawn at 30 and 120 min after surgery and assayed for plasma
      alfentanil. Morphine consumption and VAS pain scores were consistently lowest in
      group 3 over the 48 h study period. A composite measure of pain and morphine
      consumption was significantly lower in group 3 than group 2 up to 6 h after
      surgery, and significantly lower than group 1 up to 12 h. No adverse effects were
      observed. A 6-month follow-up did not reveal any significant differences among
      the three groups. It is concluded that intra-operative high dose alfentanil
      anaesthetic pre-empts post-operative pain after abdominal hysterectomy, but the
      effects are small and of short duration. Surgical procedures carried out under
      general anaesthesia using standard (and even high) doses of opioids
      intraoperatively provide suboptimal protection from the injury barrage brought
      about by incision and subsequent noxious surgical events.

PMID- 9252006
TI  - Effects of the combined oral administration of NSAIDs and dextromethorphan on
      behavioral symptoms indicative of arthritic pain in rats.
AB  - The effects of combined single oral treatments with non-steroidal anti
      inflammatory drugs (NSAIDs) and the non-competitive N-methyl-D-aspartate (NMDA)
      receptor antagonist dextromethorphan (DM) on arthritic pain were examined in a
      rat model of adjuvant-induced arthritis. Although 12.5-100 mg/kg doses of DM
      alone produced no reliable effects, treatments with ibuprofen (IB, 50 and 100
      mg/kg but not 12.5 or 25 mg/kg) produced mild analgesia in arthritic rats as
      determined using the Randall-Sellito test. IB showed a dose-response relationship
      which appeared to plateau at doses of 50 and 100 mg/kg. Adding 50 mg/kg DM to
      each IB dose resulted in significantly greater analgesic activity than IB alone
      at doses of 25, 50 and 100 mg/kg. A similar interaction between 50 mg/kg DM and
      50 mg/kg IB occurred with respect to spontaneous pain behavior. Adding 25 mg/kg
      DM to 25 mg/kg IB likewise increased analgesia as measured by both the Randall
      Sellito and spontaneous pain behavior tests (both P < 0.05). Five more NSAIDs
      were evaluated using the Randall-Sellito test, which included naproxen (NP),
      piroxicam (PIR), etodolac (ET), diclofenac (DC), and ketorolac (KE). For all six
      NSAIDS, the addition of 50 mg/kg DM reliably increased their analgesic potency,
      as indicated by reliable increases in previously effective NSAID doses (all six
      NSAIDs) as well as previously ineffective NSAID doses (IB, NP, DC, and PIR).
      These data demonstrate that DM greatly potentiates the analgesic activity of IB,
      DC, NP, PIR, ET, and KT and increases the peak effect over the NSAIDs alone.
      Similiar to DM's previously demonstrated enhancement of opioid analgesia in acute
      pain, the combination of DM and an NSAID may represent a novel analgesic approach
      to improved management of arthritic pain.

PMID- 9252007
TI  - Does electroconvulsive therapy (ECT) have any role in the management of
      intractable thalamic pain?
AB  - Three patients with intractable thalamic pain unresponsive to a range of previous
      treatments received a course of six bilateral electroconvulsive therapy (ECT)
      treatments over 2 weeks. There was no evidence of any improvement in the
      intensity of the pain, pain relief or mood as measured on visual analogue scales
      and with standard measures. Propofol was used as the anaesthetic induction agent.
      Two patients showed wide changes in blood pressure during ECT but all three
      patients showed prompt recovery. In the light of the negative findings of this
      study and those of a previous study of the use of unilateral ECT in similar
      patients it is concluded that ECT is not an effective treatment for post-stroke
      thalamic pain.

PMID- 9252008
TI  - Nociceptive responses to high and low rates of noxious cutaneous heating are
      mediated by different nociceptors in the rat: behavioral evidence.
AB  - Several lines of evidence suggest that different classes of nociceptive afferents
      mediate the responses produced by different rates of noxious skin heating. More
      specifically, low skin heating rates evoke nociceptive responses that appear to
      be mediated by the activation of capsaicin-sensitive C-fiber nociceptors, whereas
      high skin heating rates appear to produce responses mediated by the activation of
      other nociceptors. This hypothesis was examined by both electrophysiological and
      behavioral experiments. This report describes the results of experiments designed
      to determine whether pharmacologic treatments that selectively alter the activity
      of C-fiber nociceptive afferents also produce selective effects on foot
      withdrawal responses to either high or low rates of noxious foot heating. The
      results of these experiments demonstrate that: (1) topical application of a low
      concentration of capsaicin, which sensitizes C-fiber nociceptors, selectively
      decreased the latency of responses to low heating rates; (2) topical application
      of a high concentration of capsaicin, that desensitizes C-fiber nociceptors,
      selectively increased the latency of responses to low heating rates; (3) low
      doses of systemic morphine, which selectively attenuate nociception produced by
      the activation of C-fiber nociceptors, selectively increased response latencies
      for low skin heating rates. These results support the conclusion that foot
      withdrawal responses evoked by low skin heating rates are mediated by the
      activation of capsaicin-sensitive C-fiber nociceptors and foot withdrawal
      responses evoked by high skin heating rates are mediated by the activation of
      other nociceptors. This conclusion is supported by the results of the
      accompanying electrophysiological study which provides direct evidence that low
      rates of skin heating preferentially activate C-fiber nociceptors while high
      rates of skin heating preferentially activate A delta nociceptors.

PMID- 9252009
TI  - Nociceptive responses to high and low rates of noxious cutaneous heating are
      mediated by different nociceptors in the rat: electrophysiological evidence.
AB  - Behavioral nociceptive responses evoked by relatively high rates of noxious
      radiant skin heating appear to be mediated by A delta nociceptor activation,
      whereas responses evoked by low rates of skin heating appear to be mediated by
      the activation of C-fiber nociceptors. This hypothesis was confirmed by the
      results of single unit recordings of A delta and C nociceptive afferent fibers
      isolated from the saphenous nerves of pentobarbital anesthetized rats. Heating
      the hind paw skin of the rat at a relatively high rate of 6.5 degrees C/sec
      activated A delta units within 2 sec after the onset of the stimulus. This
      response latency is similar to the 2.5 sec latency of the foot withdrawal
      response to a similar stimulus. In contrast, C-fibers were only slightly
      activated at a longer latency of 5-6 sec. Conversely, heating the hind paw skin
      at a relatively low rate of 0.9 degrees C/sec activated C-fibers, but evoked only
      a few action potentials in A delta nociceptors. C-fibers began firing at a rate
      less than 1 Hz between 8 and 10 sec after the onset of heating and fired at a
      mean rate of 1.5 Hz between 10 and 12 sec, which corresponds to the latency of
      the foot withdrawal response. Topical application of capsaicin to the hind paw
      skin decreased the latency of C-fiber responses from control values of 8-12 sec
      to approximately 4 sec after topical capsaicin treatment. The mean latency of the
      foot withdrawal response to skin heating at the low rate is also reduced from
      control values of 12-14 sec to 4-5 sec after capsaicin treatment. In contrast,
      capsaicin treatment did not significantly affect the responses of A delta
      nociceptors. These results support the conclusion that nociceptive foot
      withdrawal responses to a low rate of skin heating are mediated predominantly by
      the activation of C-fiber nociceptors. These results provide direct evidence
      that, under the conditions of these experiments, nociceptive foot withdrawal
      responses evoked by high rates of skin heating are primarily mediated by A delta
      nociceptors, and foot withdrawal responses evoked by low rates of skin heating
      are primarily mediated by C-fiber nociceptors.

PMID- 9252010
TI  - Venlafaxine hydrochloride (Effexor) relieves thermal hyperalgesia in rats with an
      experimental mononeuropathy.
AB  - Venlafaxine hydrochloride (Effexor) is a structurally novel antidepressant that
      inhibits reuptake of 5-hydroxytryptamine and noradrenaline, but unlike the older
      antidepressants, has few side-effects. The objective of this study was to
      determine whether venlafaxine relieves thermal hyperalgesia in rats with
      neuropathic pain due to chronic constriction injury (CCI) of the sciatic nerve.
      Paw withdrawal latency (PWL) to heat was tested for each hind paw. A painful
      neuropathy was induced in 24 male Sprague-Dawley rats (Group 1) as described by
      Bennett and Xie. Rats randomly received either oral venlafaxine (22 mg/kg) or
      placebo via gavage feeding beginning the day after surgery. Postoperative PWL
      testing began 3 days after CCI (Time 0). A second group of 12 rats (Group 2) was
      used to confirm that venlafaxine reverses hyperalgesia in rats with a fully
      developed neuropathic lesion. These animals began to receive oral venlafaxine (22
      mg/kg) starting on the third postoperative day, after the presence of thermal
      hyperalgesia was verified through PWL testing. Testing was continued for 5 days,
      during venlafaxine administration. A third group of 12 rats (Group 3) had
      activity measured before and after treatment with venlafaxine (22 mg/kg). Rats in
      the placebo group developed thermal hyperalgesia while those that received
      venlafaxine did not. Venlafaxine also appeared to have a mild non-specific
      analgesic effect that increased PWL in the sham limb. In Group 2, thermal
      hyperalgesia was present on day 3, but following treatment with venlafaxine,
      thermal hyperalgesia resolved. Activity measurements confirmed that venlafaxine
      was not sedating in this rat model.

PMID- 9252011
TI  - Assessing the stages of pain processing: a multivariate analytical approach.
AB  - A four-stage model of pain processing was proposed, consisting of pain sensation
      intensity, pain unpleasantness (stage 1 affect), suffering (stage 2 affect), and
      pain behavior. We studied 506 chronic pain patients (230 male and 276 female)
      using a multivariate statistical technique (LISREL) in order to demonstrate the
      structural relationship among multiple indicators of pain processing; and to
      characterize these stages in terms of their interactions. A strong relationship
      was revealed between the majority of the underlying indicators of each pain
      processing stage. A linear stage sequence best fitted the relationship between
      the four stages. Successive stages did not have recursive effects on earlier pain
      components. A confirmatory LISREL analysis was conducted with an additional
      sample of 502 chronic pain patients. In this replication analysis the structural
      equation model consisted of pain intensity, unpleasantness (stage 1 affect),
      emotional suffering (stage 2 affect), and pain behavior. This study extends the
      validation of these pain dimensions, as well as the validity of the measure(s) of
      each separate stage.

PMID- 9252012
TI  - Involvement of NMDA receptor mechanisms in jaw electromyographic activity and
      plasma extravasation induced by inflammatory irritant application to
      temporomandibular joint region of rats.
AB  - The aim of this study was to examine the possible role of N-methyl-D-aspartate
      (NMDA) receptor mechanisms in responses induced by the small-fibre excitant and
      inflammatory irritant mustard oil injected into the temporomandibular joint (TMJ)
      region of rats. The effects of the non-competitive NMDA antagonist MK-801 were
      tested on the mustard oil-evoked increases in electromyographic (EMG) activity of
      the masseter and digastric muscles and Evans Blue plasma extravasation. Five
      minutes before the mustard oil injection, MK-801 or its vehicle was administered
      systemically (i.v.), into the third ventricle (i.c.v.), or locally into the TMJ
      region. Compared with control animals receiving vehicle, the rats receiving MK
      801 at an i.v. dose of 0.5 mg/kg (n = 5) showed a significant reduction in the
      incidence and magnitude of EMG responses as well as in the plasma extravasation
      evoked by mustard oil; MK-801 at an i.v. dose of 0.1 mg/kg (n = 5) had no
      significant effect on plasma extravasation or on the incidence and magnitude of
      EMG responses but did significantly increase the latency of EMG responses. An
      i.c.v. dose of 0.1 mg/kg (n = 5) or 0.01 mg/kg (n = 5) had no significant effect
      on plasma extravasation or incidence of EMG responses but did significantly
      reduce the magnitudes of the masseter EMG response; the 0.01 mg/kg dose also
      significantly increased the latency of the digastric EMG response. The magnitudes
      of both the masseter and digastric EMG responses were also significantly reduced
      by MK-801 administered into the TMJ region at a dose of 0.1 mg/kg (n = 5) but not
      by 0.01 mg/kg (n = 5); neither dose significantly affected the incidence of EMG
      responses or the plasma extravasation. These data suggest that both central and
      peripheral NMDA receptor mechanisms may play an important role in EMG responses
      evoked by the small-fibre excitant and inflammatory irritant mustard oil, but
      that different neurochemical mechanisms may be involved in the plasma
      extravasation induced by mustard oil.

PMID- 9252013
TI  - Lamotrigine control of central pain.
AB  - Central pain remains a therapeutic challenge. We report beneficial effects of
      lamotrigine, a novel antiepileptic drug, on four patients suffering from long
      standing central pain. Analgesia may be due to interference with glutamatergic
      transmission.

PMID- 9252014
TI  - The lateralization of back pain is sex-related?

PMID- 9252015
TI  - The preglomerular nucleus of gymnotiform fish: relay station for conveying
      information between telencephalon and diencephalon.
AB  - The preglomerular nucleus of teleost fishes, believed to be a lateral part of the
      posterior tuberculum in the diencephalon, receives input from several sensory
      areas. By employing an in vitro technique, the pattern of connectivity between
      this cell group and the telencephalon has been explored through retrograde and
      anterograde tracing in the gymnotiform fish Apteronotus leptorhynchus. Neurons of
      the preglomerular nucleus project to the following telencephalic areas: central
      division of dorsal forebrain, dorsal subdivision of dorsolateral telencephalon,
      posterior subdivision of dorsolateral telencephalon, dorsal posterior
      telencephalon, and probably, also subdivision 2 of dorsomedial telencephalon.
      Experiments in which tracer application was restricted to the lateral subdivision
      of the preglomerular nucleus, or in which tracer substance was placed into
      various regions of the telencephalon revealed a differential projection pattern
      of cells in the lateral and the medial subdivision of the preglomerular nucleus.
      Neurons in the central division of the dorsal forebrain, the dorsal posterior
      telencephalon, and likely, also in the subdivision 2 of the dorsomedial
      telencephalon and the ventricular zone of the intermediate subdivision of the
      ventral telencephalon project back to the preglomerular nucleus. Thus, a major
      function of the preglomerular nucleus appears to be to act as a relay station for
      conveying information between diencephalon and telencephalon.

PMID- 9252016
TI  - Intense peripheral electrical stimulation evokes brief and persistent inhibition
      of the nociceptive tail withdrawal reflex in the rat.
AB  - In a study of modulation of nociception by sensory inputs, electrical stimulation
      was applied to specific sites in the hindlimb and effects on the nociceptive tail
      withdrawal reflex were monitored in the lightly anaesthetized rat. Stimulation
      was applied to previously defined sites in the hindlimb, meridian points femur
      futu (ST-32), fengshi (GB-31) and zusanli (ST-36). It consisted of a 4 Hz train
      of 2 ms square pulses given for 20 min at 20 x the threshold intensity required
      for muscle twitch. Tail withdrawal was provoked by application of a noxious heat
      stimulus applied to the tip of the tail. Results were expressed as a percentage
      of the maximal possible inhibition which is achieved when the post-treatment
      latency is 2 x the pre-treatment latency otherwise known as the cut off. During
      stimulation, the latency of the withdrawal increased to approximately 70% of the
      maximal possible inhibition. Following stimulation, the inhibition persisted for
      > 1 h. Stimulation at 2 or 6 Hz elicited similar effects but stimulation at 8 Hz
      evoked inhibition during the stimulation only. Stimulation applied to sites away
      from defined meridian points inhibited tail withdrawal during the stimulation; no
      post-stimulation effect was produced. In acutely transected animals (< or = 48
      h), stimulation of meridian points elicited a small, brief increase in latency
      but during stimulation only. At 7 and 14 days after spinal transection, this
      response during stimulation was greater in magnitude and a brief post-stimulation
      increase was also observed. The return of this latter effect was coincident with
      the return of bladder function. These data suggest that high intensity, low
      frequency electrical stimulation of hindlimb meridian points in the lightly
      anaesthetized rat produces both brief and persistent inhibitory effects on the
      nociceptive tail withdrawal reflex. These effects appear to be elicited by
      different mechanisms. The persistent effect may represent a plastic change in
      central inhibitory mechanisms. Data from spinal animals indicate a major
      participation of supraspinal structures but that spinal mechanisms are also
      capable of sustaining both types of effect.

PMID- 9252018
TI  - Serotonergic innervation of the supraependymal neuronal complex of the golden
      hamster.
AB  - A ganglion-like system of intraventricular neuronal perikarya and processes known
      as the supraependymal neuronal complex (SENC) is located on the floor of the
      third ventricle of the golden hamster. Serotonergic neuronal elements were
      identified in the SENC by immunocytochemical techniques. Serotonin (5
      hydroxytryptamine, 5-HT) was not detected within supraependymal neuronal
      perikarya. However, serotonergic nerve fibers were found to project via the
      median eminence both onto the surface and into the neuropil of the SENC. The SENC
      is thought to be involved in neuroendocrine regulation since it innervates the
      pituitary gland. The results of the present study suggest that serotonin plays a
      role in SENC/pituitary gland interaction.

PMID- 9252017
TI  - The role of paraventricular nucleus of hypothalamus in stress-ulcer formation in
      rats.
AB  - The rat stress model of restraint and cold water immersion was used to
      investigate the effect of stimulating the paraventricular nucleus (PVN) of
      hypothalamus on the development of stress-induced gastric ulceration. The results
      were (1) electric stimulation of the PVN increased the stress ulceration, while
      electrolytic lesion of the PVN decreased it; (2) intracerebroventricular
      injection (i.c.v.) of acetylcholine (Ach) enhanced the effect of PVN stimulation
      on stress ulcers, and the M-receptor was involved; (3) i.c.v. norepinephrine (NE)
      attenuated the effect of PVN stimulation on stress ulcers in a dose-dependent
      manner, and the beta-receptor was involved; (4) i.c.v. 5-hydroxytryptamine (5-HT)
      enhanced the effect of PVN stimulation on stress ulcers; (5) electrolytic lesions
      of dorsal raphe nucleus (DR) attenuated the effect of PVN stimulation on stress
      ulcers, while electrolytic lesions of the locus ceruleus (LC) aggravated the
      effect; (6) thyroidectomy, adrenalectomy, ovariectomy, vagotomy and sympathectomy
      all attenuated the effect of PVN stimulation on stress ulcers; (7) electric
      stimulation of the PVN produced no effect on gastric juice volume, acidity, total
      acid output, pepsin activity or the gastric barrier mucus; but greatly reduced
      gastric mucosal blood flow. These results indicate that the PVN is an important
      brain site regulating the development of stress-induced gastric ulcers, that the
      classical neurotransmitters Ach, NE and 5-HT are involved, and that in the
      periphery, both the parasympathetic and sympathetic nervous systems and the three
      endocrine glands (thyroid, adrenal and gonad) take part in the effect.

PMID- 9252019
TI  - Audiogenic kindling increases neuronal responses to acoustic stimuli in neurons
      of the medial geniculate body of the genetically epilepsy-prone rat.
AB  - Frequent repetition of audiogenic seizure (AGS) ('AGS kindling') in the severe
      substrain of genetically epilepsy-prone rats (GEPR-9s) results in the appearance
      of cortical epileptiform electrographic activity, increases of seizure duration
      and additional convulsive behaviors. These findings suggest that the initial AGS
      network, which is located primarily in the brainstem, has undergone expansion to
      the forebrain. The medial geniculate body (MGB) is a thalamic structure that is
      the first major auditory nucleus efferent to the AGS-initiating site in the
      inferior colliculus. The MGB is not required for AGS induction, but it has been
      implicated in the expanded AGS network in GEPR-9s based on focal, pharmacological
      blockade experiments. The present study examined changes in acoustically evoked
      MGB neuronal responses in awake and behaving GEPR-9s and in anesthetized GEPR-9s
      after 14 repetitive AGS-inducing stimuli given daily. An elevated number of
      action potentials was observed in the MGB neuronal responses after AGS kindling
      in GEPR-9s. This increase of MGB neuronal responses was associated with a loss of
      habituation and lasted for at least 28 days after the 14th AGS. An increase in
      the incidence of sustained acoustic responses in MGB neurons was observed after
      repetitive AGS in GEPR-9s. Increases in the peak latency and threshold of MGB
      neuronal responses were also observed after AGS kindling. MGB neurons exhibited a
      rapid tonic firing during tonic seizures in behaving GEPR-9s, suggesting that the
      MGB may be implicated in the propagation of seizure activity. However, MGB
      neuronal firing was silent during post-tonic clonus, a behavior seen in GEPR-9s
      only after AGS repetition, suggesting that MGB does not play a direct role in the
      generation of this convulsive behavior. Thus, changes in neuronal firing in
      nuclei efferent to the MGB, in the expanded neuronal network for repetitive AGS,
      may be responsible for the generation of post-tonic clonus in GEPR-9s.

PMID- 9252020
TI  - Effects of interleukin-1beta and mild stress on alterations of norepinephrine,
      dopamine and serotonin neurotransmission: a regional microdialysis study.
AB  - The effects of systemically administered interleukin-1beta (1.0 microg) on in
      vivo variations of monoamines was assessed in several brain regions.
      Administration of the cytokine provoked a modest increase of extracellular 5-HIAA
      and HVA from the nucleus accumbens, and 5-HIAA from the hippocampus. Following
      mild neurogenic stressor (application of a series of air puffs), a still greater
      increase of accumbal 5-HIAA and HVA was evident, a transient increase of
      hippocampal 5-HT was noted and the 5-HIAA increases were augmented. Additionally,
      while the air puff stress was without effect on DOPAC and HVA in the prefrontal
      cortex of saline treated rats, a significant rise of these metabolites was
      apparent in rats treated with the cytokine. It appears that interleukin-1
      administration may have effects on forebrain monoamines, and also results in
      greater neuronal reactivity to mild neurogenic stressors. This study reveals that
      although effects of neurogenic stressors (air puffs) and cytokine (somatic
      stressor) may share some similarities (e.g., HPA activation), the pattern of
      central neurochemical changes elicited by the cytokine could be distinguished
      from that induced by a more neurogenic stressor (air puffs), and that these
      effects showed selective synergism. These data also lend support to the
      contention that neurogenic stressors may have a much greater impact on central
      neurotransmission under conditions of immune activation.

PMID- 9252022
TI  - Demonstration of the facilitatory role of 8-OH-DPAT on cholinergic transmission
      in the rat hippocampus using in vivo microdialysis.
AB  - The role of the serotonin (5-HT)1A receptor in the regulation of acetylcholine
      (ACh) release in the hippocampus was investigated using an in vivo microdialysis
      technique and a sensitive radioimmunoassay specific for ACh. The mean (+/-
      S.E.M.) basal ACh contents in the hippocampal perfusate of conscious, freely
      moving rats was 60 +/- 4 (n = 29) and 3691 +/- 265 fmol/30 min (n = 31),
      respectively, in the absence and presence of physostigmine (Phy) in the perfusion
      fluid. Systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH
      DPAT, 0.5 mg/kg, s.c.), a 5-HT1A agonist, significantly enhanced ACh release both
      in the presence and absence of Phy. Local application of 8-OH-DPAT (3-30 microM)
      into the hippocampus through the microdialysis probe significantly potentiated
      ACh release only in the presence of Phy, whereas no significant effect was
      observed in its absence. Pretreatment with NAN-190 (3 mg/kg, i.p.), a 5-HT1A
      antagonist, eliminated the increasing effect of systemically applied 8-OH-DPAT on
      ACh release, while NAN-190 alone had no effect on basal ACh release either in the
      absence or presence of Phy. Consistent with the time course of ACh release,
      systemic administration of 8-OH-DPAT evoked hyperlocomotion, which was reversed
      by NAN-190. However, local hippocampal application of 8-OH-DPAT did not affect
      the locomotor activity of the rats. These findings suggest that at least two
      different sites are involved in the 8-OH-DPAT-induced increase in the release of
      ACh in the rat hippocampus in vivo.

PMID- 9252021
TI  - Dopamine, as well as norepinephrine, is a link between noradrenergic nerve
      terminals and splenocytes.
AB  - The effect of supramaximal electric field stimulation on 3H released from rat
      spleen strips was studied after loading with either [3H]dopamine ([3H]DA) or
      [3H]norepinephrine ([3H]NE). In some experiments, [3H]DA and [3H]NE stored in the
      tissue or released in response to electrical stimulation were separated from
      their tritiated metabolites using HPLC followed by radiochemical detection. The
      stimulation-evoked release of 3H after loading with either derivative was subject
      to negative feedback modulation through alpha2-adrenergic, D2-dopamine and
      muscarinic acetylcholine receptors, and could be prevented by either calcium
      removal or tetrodotoxin blocking of Na+ influx, indicating its neuronal and
      vesicular origin. After the separation of radioactive metabolites by HPLC, both
      the tissue loaded with [3H]DA and the fractions collected during electrical
      stimulation contained a considerable amount of [3H]NE, providing evidence that
      the neurons it originated from were adrenergic in function. [3H]DA was also
      released during electrical stimulation. Since the spleen does not receive
      dopaminergic innervation, it was concluded that the noradrenergic axon terminals
      in the spleen were able to take up DA, convert it in part into NE, and release it
      as both DA and NE in response to neural activity. The ratio of [3H]DA and [3H]NE
      in the spleen loaded with [3H]DA was found to be dependent on both temperature
      and time of loading, and could be modulated by various drugs such as
      desmethylimipramine, a NE uptake blocker, and disulfiram or fusaric acid,
      dopamine beta-hydroxylase inhibitors. The phenomenon may reveal a new mechanism
      by which immunocytes in the spleen can be regulated by the neuroendocrine system.

PMID- 9252023
TI  - Cholinergic deficits in aged rat spinal cord: restoration by GM1 ganglioside.
AB  - Cholinergic neurons of spinal cord are central for the processing of motor,
      autonomic, and sensory modalities. Aging is associated with a variety of motor
      and autonomic symptoms that might be attributed, in part, to impaired spinal cord
      function. We found that cholinergic neurochemistry is diminished in the spinal
      cord of 22-24-month-old rats compared with 3-month-old rats. Choline
      acetyltransferase, high-affinity choline transport and hemicholinium-3 binding to
      the choline carrier were reduced in the aged spinal cord. The activity of the
      choline transporter and the hemicholinium-3 binding were decreased in all spinal
      segments, cervical, thoracic, lumbar and sacral. Hemicholinium-3 binding was
      reduced in ventral and dorsal horns along all spinal segments. The activity of
      choline acetyltransferase was decreased only in cervical and lumbar cord.
      Treatment of aged animals with GM1 induced the recovery of the presynaptic
      cholinergic markers in the aged spinal cord.

PMID- 9252024
TI  - In sympathetic but not sensory neurones, phosphoinositide-3 kinase is important
      for NGF-dependent survival and the retrograde transport of 125I-betaNGF.
AB  - The way in which the same ligands and receptors have different functional effects
      in different cell types must depend on subtle differences in the second messenger
      cascades. Sensory and sympathetic neurones both retrogradely transport nerve
      growth factor (NGF) and depend on NGF for their developmental survival. NGF
      binding to the high affinity tyrosine kinase (TrkA) receptors initiates second
      messenger signalling cascades, one of which includes the activation of
      phosphoinositide-3 kinase (PI3-kinase). We demonstrate that 100-fold higher
      concentrations of the PI3-kinase inhibitor, Wortmannin, are required to inhibit
      the survival effects and retrograde axonal transport of NGF in sensory neurones
      than in sympathetic neurones. Similarly, although less potently than Wortmannin,
      the PI3-kinase inhibitor LY294002 required a 10-fold higher concentration to
      inhibit the survival effects of NGF in sensory than in sympathetic neurones.
      Inhibitors of other second messengers, including staurosporine, pertussis and
      cholera toxins, failed to have an effect on the transport of the NGF receptor
      complex in both cell types. Also, Wortmannin did not affect the structural
      integrity of the sympathetic nerve terminals. As PI3-kinase is present in both
      neuronal populations, this suggests that the Wortmannin sensitive isoform of PI3
      kinase (p110) is essential in sympathetic neurones both for survival and for NGF
      TrkA receptor complex trafficking. As sensory neurones also depend on NGF for
      their developmental survival and endocytose and retrogradely transport the NGF
      TrkA receptor complex, this population of neurones may either recruit a different
      isoform of PI3-kinase or utilize PI3-kinase independent signalling pathways for
      these cellular functions.

PMID- 9252025
TI  - Aberrant neuronal responsiveness in the genetically epilepsy-prone rat: acoustic
      responses and influences of the central nucleus upon the external nucleus of
      inferior colliculus.
AB  - The inferior colliculus (IC) central nucleus (ICc), is critical for audiogenic
      seizure (AGS) initiation in the genetically epilepsy-prone rat (GEPR). The ICc
      lacks direct motor outputs but sends a major projection to the external nucleus
      of IC (ICx), which does project to the sensorimotor integration nuclei within the
      AGS neuronal network. The present study compared acoustic responses of ICx
      neurons in the GEPR and normal anesthetized rat and evaluated whether the GEPR
      exhibits functional abnormalities in the pathway from ICc to ICx. There is a
      significantly greater incidence of sustained repetitive response patterns to the
      acoustic stimulus in GEPR ICx neurons (75%) than in normal ICx neurons (24%).
      Following unilateral microinjection of N-methyl-D-aspartate (NMDA) into the
      contralateral ICc, acoustically-evoked ICx excitation and inhibition were each
      increased in normal animals, which is consistent with the mixed projections
      previously reported in this pathway and observed with electrical stimulation in
      the present study. The NMDA-induced ICx firing increase may be relevant to AGS,
      since, in previous studies, bilateral focal microinjection of NMDA into the ICc
      induced AGS susceptibility in normal rats [23]. However, the incidence and degree
      of the ICx neuronal response changes after NMDA microinjection was not abnormal
      in the GEPR. These data suggest that the hyperresponsiveness of ICx neurons may
      not involve abnormal transmission between the ICc and ICx, despite the elevated
      ICx neuronal responses to acoustic stimuli. However, the ICx hyperresponsivess of
      the GEPR, which is likely due to the known decrease in effectiveness of GABA
      mediated inhibition in GEPR neurons, may be a major mechanism subserving the
      critical role that this structure plays in the AGS network.

PMID- 9252026
TI  - Proline-induced potentiation of glutamate transmission.
AB  - The amino acid proline has long been suspected to serve as a modulator of
      synaptic transmission in the mammalian brain, but no such function has been
      identified. The selective expression of high affinity proline transport by a
      subset of glutamate pathways suggested that proline might play a role in synaptic
      transmission at these sites. This idea was tested with use of one such pathway,
      the Schaffer collateral-commissural projection to CA1 pyramidal cells of the rat
      hippocampus. Proline enhanced the initial slope of the field EPSP without
      affecting axonal excitability or the magnitude of paired-pulse facilitation.
      Proline-induced potentiation far outlasted the period of proline application and
      required the activation of NMDA receptors. Proline enhanced Schaffer collateral
      commissural synaptic transmission even when the connections between areas CA1 and
      CA3 had been interrupted. Potentiation was observed with a proline concentration
      normally present in human CSF (3 microM). A concentration typical of CSF in
      persons with the genetic disorder hyperprolinemia type II (30 microM) produced a
      somewhat greater effect. Occlusion experiments suggested that proline-induced
      potentiation and tetanus-induced long-term potentiation utilize largely distinct
      transduction mechanisms. Proline-induced potentiation could be blocked by a prior
      high frequency stimulus, whether or not the stimulus evoked long-term
      potentiation. These results suggest that endogenous extracellular proline
      regulates the basal function of some glutamate synapses by maintaining them in a
      partially potentiated state. They may also facilitate understanding of the
      seizures and/or mental retardation associated with genetic disorders of proline
      metabolism.

PMID- 9252028
TI  - Excessive oxygen or glucose supply does not alter the blood flow response to
      somatosensory stimulation or spreading depression in rats.
AB  - We investigated the influence of hyperoxia (arterial pO2 446 +/- 43 mmHg) and
      hyperglycemia (blood glucose 19.4 mmol/l) on somatosensory stimulation (whisker
      deflection) employing laser Doppler flowmetry (LDF). Our aim was to test the
      hypothesis that a possible substrate-sensing mechanism for glucose and oxygen
      contributes to the coupling between cortical activity and regional cerebral blood
      flow (rCBF) in order to match increased demand with substrates. In addition, we
      looked at the influence of hyperglycemia (blood glucose 17.9 mmol/l) and
      hypercapnia (arterial pCO2 62 mmHg) on rCBF (LDF) and regional cerebral blood
      oxygenation changes (rCBO) in the even stronger metabolic stimulus of cortical
      spreading depression (CSD). For the latter we employed the new non-invasive
      technique of near infrared spectroscopy (NIRS). All experiments were done using
      chloralose/urethane-anesthetized rats. Somatosensory stimulation increased rCBF
      by about 20% of baseline, in the case of both norm- and hyperoxia as well as both
      normo- and hyperglycemia. The blood-flow response to CSD consisted of a temporary
      sharp increase in rCBF to more than 400%. At the same time, the concentration of
      oxyhemoglobin [HbO2] increased, while deoxyhemoglobin [Hb] decreased, indicating
      excessive oxygenation. Hyperglycemia altered neither the rCBF nor the rCBO
      response. Preexisting hypercapnia, however, produced reductions in both
      hyperperfusion (rCBF) and hyperoxygenation (rCBO) during CSD. We found that, for
      experimental hyperglycemia, i.v. may be superior to i.p. application of glucose
      because of the latter's side effects in connection with blood flow. Our findings
      cannot support the hypothesis of a substrate sensing mechanism in coupling.

PMID- 9252027
TI  - Cardiovascular effects of central administration of clonidine in conscious cats.
AB  - The effects on arterial blood pressure and heart rate after an
      intracerebroventricular (i.c.v.) administration of clonidine were investigated
      using conscious normotensive cats. Injection of clonidine (5-10 microg; 5 microl;
      i.c.v.) elicited a decrease in mean arterial pressure (MAP) and heart rate (HR)
      in a dose-dependent manner. The highest dose of 10 microg of clonidine decreased
      MAP and HR by 39 +/- 3 mmHg and 74 +/- 5 b.p.m., respectively (n = 7).
      Pretreatment with yohimbine, the alpha2-adrenoceptor antagonist (8 microg; 5
      microl; i.c.v.) blocked the cardiovascular responses to a subsequent i.c.v.
      injection of 10 microg clonidine (n = 7). Furthermore, preadministration of
      cimetidine (100 microg; 5 microl; i.c.v.), the H2 histamine receptor antagonist
      with imidazoline receptor activating properties, prevented the decreases in MAP
      and HR to a subsequent i.c.v. injection of 10 microg clonidine (n = 7). By
      contrast, pretreatment with the specific I1 imidazoline receptor blocker,
      efaroxan (100-500 microg; 5 microl; i.c.v.), failed to inhibit the cardiovascular
      effects of an i.c.v. administration of 10 microg clonidine (n = 7). These results
      suggest that the effects of centrally administered clonidine on MAP and HR are
      probably not mediated through activation of the I1 subtype of imidazoline
      receptors in conscious cats. However, the cardiovascular effects elicited by
      i.c.v. administration of clonidine appear to result from stimulation of central
      alpha2-adrenergic or the H2 histaminergic-like receptors.

PMID- 9252029
TI  - Effect of long-term administration of ethyl eicosapentate (EPA-E) on local
      cerebral blood flow and glucose utilization in stroke-prone spontaneously
      hypertensive rats (SHRSP).
AB  - The objective of this study was to determine the effect of ethyl eicosopentate
      (EPA-E) on local cerebral blood flow (1-CBF) and local glucose utilization (1
      CGU) in specific regions of the brain in stroke-prone spontaneously hypertensive
      rats (SHRSP). EPA-E (100 mg/kg body weight) or saline was orally administered to
      8-week-old SHRSP. L-CBF and 1-CGU in the EPA-E-treated, saline-treated, and 8
      week-old control rats were measured autoradiographically using 14C-iodoantipyrine
      and 14C-deoxyglucose (Sakurada's and Sokoloff's methods). The 1-CBF of the saline
      treated group decreased significantly with age in all areas measured. EPA-E
      treatment alleviated the age-dependent decrease in 1-CBF in all areas, especially
      those in the basal ganglia. The 1-CGU of the saline-treated group did not change
      with age, however EPA-E treatment increased 1-CGU in all areas measured, though
      the changes were not significant. EPA-E ameliorated the decrease in cerebral
      blood flow and improved glucose metabolism in SHRSP suffering from severe
      hypertension. These results suggest that EPA-E may be useful in the prevention of
      stroke.

PMID- 9252030
TI  - Changes in neuropeptide Y immunoreactivity in the arcuate nucleus during and
      after food restriction in lactating rats.
AB  - Previous studies have demonstrated that food restriction during lactation extends
      the length of lactational infertility in rats. In order to determine whether
      Neuropeptide Y (NPY) plays a role in the increased length of lactational
      infertility seen in food-restricted rats, NPY immunoreactivity in the arcuate
      nucleus of lactating rats that were ad lib fed or food restricted from Day 8 to
      14 postpartum was compared. Food-restricted rats showed higher numbers of NPY
      stained cells at the end of the food-restriction period (Day 15 postpartum) than
      did ad lib-fed rats at the same stage of lactation. This difference persisted
      until Day 25 postpartum although all animals were fed ad libitum from Day 15
      onwards. Switching litters between ad lib-fed and food-restricted females from
      Day 15 until Day 20 postpartum did not eliminate the difference in NPY
      immunoreactivity between the two diet conditions. Given that food restriction
      during lactation leads to a prolonged suppression of LH release that also
      persists after refeeding and is not affected by the nutritional status of the
      litter, these data are consistent with a role for NPY in the prolonged
      suppression of reproductive function seen in food restricted lactating rats.

PMID- 9252031
TI  - Effect of an NMDA receptor antagonist on the wind-up of neurons in the trigeminal
      oralis subnucleus.
AB  - Extracellular recordings of convergent neurons of the oralis subnucleus of the
      trigeminal sensory complex were performed in paralysed rats under halothane-N2O
      O2 anesthesia using glass micropipettes. The effects of MK801, a noncompetitive
      NMDA receptor antagonist, were observed on the increased cell activity (wind-up),
      triggered by the repetition, at a low frequency (0.66 Hz) and high intensity (3
      times the threshold of C-fiber response), of electrical stimulation of the
      receptive field. Successive cumulative doses (up to 1 mg/kg) of MK801 i.v.
      resulted in a dose-dependent decrease in the responses related to C-fiber input
      (11 cells). A single dose of 1 mg/kg applied in four cells had effects similar to
      the 1 mg/kg dose given cumulatively. Three units were either weakly or not
      modified by MK801. In a second experiment, recordings were performed in 12 cells
      for 80 min after an injection of a small dose of MK801 (0.15 mg/kg). C input was
      not significantly modified by the antagonist. The effects of MK801 on the first
      part of the wind-up response (wind-up proper) peaked between 15 and 50 min and
      returned to control values at about 80 min. The effects on the postdischarge
      followed approximately the same time course. It is concluded that despite being
      devoid of substantia gelatinosa, the oralis subnucleus contains neurons that
      display an NMDA receptor-linked wind-up similar to the phenomenon described in
      the dorsal horn of the spinal cord.

PMID- 9252032
TI  - Differential glutamate immunoreactivity in glial cells of the retino-recipient
      layer of the viper optic tectum following retinal ablation. A quantitative EM
      immunogold study.
AB  - In normal conditions, retino-tectal terminals are densely glutamate
      immunoreactive. During the degenerative process of these terminals, a significant
      increase of glutamate immunoreactivity has been exclusively observed in
      microglial cells. It is suggested that this phenomenon is consecutive to the
      synthesis of glutamate by these cells after their activation by degenerating
      optic terminals.

PMID- 9252034
TI  - Anorexia, weight loss and increased plasma interleukin-6 caused by chronic
      intracerebroventricular infusion of interleukin-1beta in the rat.
AB  - Pro-inflammatory cytokines produced in the central nervous system (CNS) have been
      suggested to have a role in the anorexia and cachexia of disease. In the present
      study, the effects of chronic exposure of the CNS to interleukin-1beta (IL-1beta)
      on several indicators of cachexia were studied. Rats were prepared with an
      intracerebroventricular (i.c.v.) cannula and an osmotic minipump that delivered
      vehicle or 1.56 ng/h recombinant murine IL-1beta for 4 days. Food intake and body
      weight were determined daily during the 4-day infusion period and plasma IL-6 and
      corticosterone concentrations were determined from plasma collected postinfusion.
      Chronic i.c.v. infusion of IL-1beta resulted in a chronic reduction in food
      intake. Rats infused i.c.v. with IL-1beta ate less food each day compared to
      vehicle controls and, at the end of the 4-day infusion period, consumed an
      average of 17.2 g less. Intracerebroventricular infusion of IL-1beta also caused
      an immediate and substantial loss of body weight that was sustained throughout
      the infusion period. In addition, rats infused with IL-1beta had plasma levels of
      IL-6 double those of vehicle controls (401 pg/ml vs. 185 pg/ml). Plasma
      corticosterone concentrations were similar between treatments. These results
      suggest that chronic exposure of the CNS to cytokines such as IL-1beta may be
      sufficient to induce anorexia and cachexia.

PMID- 9252033
TI  - omega-Conotoxin GVIA and desipramine insensitive norepinephrine efflux from
      cardiac sympathetic nerve terminal.
AB  - Using dialysis technique, prominent accumulation of norepinephrine (NE) in the
      myocardial interstitial space was observed under local administration of a
      monoamine oxidase inhibitor (pargyline, 10 mM), and a vesicle uptake inhibitor
      (reserpine, 10 microM). Accumulation of NE in the myocardial interstitial space
      was associated with a reduction of dihydroxyphenylglycol levels. Pretreatment
      with omega-conotoxin GVIA (10 microM) or desipramine (10 microM) did not suppress
      this response. A brisk increase in dialysate NE levels might occur as a
      consequence of exocytotic or neurotransporter insensitive efflux of NE.

PMID- 9252035
TI  - 17beta-Estradiol protects against NMDA-induced excitotoxicity by direct
      inhibition of NMDA receptors.
AB  - Several lines of evidence suggest that 17beta-estradiol (betaE2) has
      neuroprotective properties. The risk and severity of dementia are decreased in
      women who have received estrogen therapy, and betaE2 protects neurons in vitro
      against death from a variety of stressors. Neuroprotection by betaE2 has been
      suggested to be due to free radical scavenging. We demonstrate an additional
      neuroprotective mechanism whereby betaE2 protects against NMDA-induced neuronal
      death by directly inhibiting the NMDA receptor.

PMID- 9252036
TI  - Involvement of endogenous opioids and ATP-sensitive potassium channels in the
      mediation of carbachol-induced antinociception at the spinal level: a behavioral
      study in rats.
AB  - The effects of intrathecally administered (i.t.) atropine, glibenclamide, a
      blocker of ATP-sensitive potassium channels, or naloxone on the antinociception
      produced by i.t. carbachol or morphine were observed in rats by tail-flick (TF)
      test. The results showed that: (1) i.t. carbachol produced a dose-dependent
      antinociception and it could be antagonized by i.t. atropine; (2) the
      antinociception produced by i.t. carbachol could be blocked dose-dependently by
      i.t. glibenclamide or i.t. naloxone; (3) the antinociception produced by i.t.
      morphine could be blocked dose-dependently by i.t. glibenclamide, but not by i.t.
      atropine. The results suggest that the antinociception produced by activation of
      muscarinic receptors at the spinal level might be mediated by endogenous opioids
      and ATP-sensitive potassium channels in a cascade form.

PMID- 9252037
TI  - Coordinate reduction in cell proliferation and cell death in mouse olfactory
      epithelium from birth to maturity.
AB  - We investigated cell proliferation and cell death in the olfactory epithelium
      (OE) of mice from birth to maturity using bromodeoxyuridine and terminal
      deoxynucleotidyl transferase nick end labeling. We show that cell death events
      and proliferative activity diminish concomitantly with age in the OE. Thus, the
      age-dependent and coordinate diminution in cell proliferative activity and cell
      death events may serve to maintain the thickness of the OE as mice mature and
      age.

PMID- 9252038
TI  - Hemispheric asymmetries in spontaneous firing characteristics of substantia nigra
      pars reticulata neurons following a unilateral 6-hydroxydopamine lesion of the
      rat nigrostriatal pathway.
AB  - Single unit activity of substantia nigra pars reticulata (SNR) neurons was
      recorded bilaterally in rats subjected to unilateral 6-hydroxydopamine lesions of
      the ascending mesostriatal dopaminergic pathway, resulting in an almost complete
      loss of dopaminergic neurons in the ipsilateral SN pars compacta. Firing rate and
      firing pattern of SNR neurons in lesioned rats were compared with respective data
      from sham-lesioned rats and naive controls. In lesioned rats, the mean firing
      rate of SNR neurons at the lesioned side was significantly reduced and there was
      an increase in the occurrence of bursting activity. In contrast, firing rate in
      the contralateral SNR was significantly increased without change in the frequency
      of bursting neurons. This asymmetrical change in spontaneous firing
      characteristics of SNR neurons following the lesion could be involved in the
      complex behavioral changes seen in this model of Parkinson's disease.

PMID- 9252039
TI  - Issues in the development of medical products based on human plasma.
AB  - Product development and process validation are shown in the case of several
      products obtained from human plasma. These are virus-inactivated plasma,
      intravenous immunoglobulins and the clotting factors VIII and IX. Different
      analytical methods are presented, which are used for product control and in
      process control. For the production of virus-inactivated human plasma a down
      scale protocol is presented, allowing a simulation of the production on a
      laboratory scale. Virus validation has shown that the reduction of transfusion
      relevant viruses in the process was higher than six log steps. Determination of
      leachables from the RP-column, which was used in this production, proved that
      they appear in the final product in quantities below the detection limits only.
      It was also shown that the chemicals used for virus inactivation could be
      quantitatively removed from the product. For the isolation of other products,
      here intravenous gamma globulins and the clotting factors VIII and IX, similar
      validation steps had to be taken. In the case of clotting factor VIII the
      following data were determined, the reduction of viruses, the amount of
      leachables from the column, the residues of chemicals from the solvent/detergent
      treatment for virus inactivation. Virus reduction was successfully performed as
      well as the removal of chemicals used for virus inactivation. The amount of
      leachables from the columns used for chromatographic purification was found to be
      far below the permissible levels.

PMID- 9252040
TI  - Isolation and measurement of urinary 8-iso-prostaglandin F2alpha by high
      performance liquid chromatography and gas chromatography-mass spectrometry.
AB  - 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha) is a product of free radical
      catalyzed peroxidation of arachidonic acid. Measurement of its urinary excretion
      has been proposed as an index of oxidative status in vivo. A stable isotope
      dilution method for its quantification by gas chromatography-electron capture
      chemical ionization mass spectrometry is described. Sample cleanup required the
      combined use of high-performance liquid chromatography and thin-layer
      chromatography. The inter-assay R.S.D. in two separate determinations was 1.6
      (n=4) and 2.3% (n=4). The accuracy of the assay was evaluated through recovery
      experiments. The equation of the regression plot correlating the amounts added
      and recovered was y=0.91x-0.31, r=0.9916 (n=12). The pair of fragment ions ([M
      181]-) at m/z 569 and m/z 573 was monitored for quantification. The mean 8-iso
      PGF2alpha excretion rate was 528 +/- 127 (S.D.) ng per day in five male
      volunteers and 730 +/- 305 ng per day in six females. Intake of 80 mg of lycopene
      per day by eleven volunteers for four weeks resulted in a non-significant
      reduction of 8-iso-PGF2alpha excretion.

PMID- 9252041
TI  - Simultaneous determination of eight lipid peroxidation degradation products in
      urine of rats treated with carbon tetrachloride using gas chromatography with
      electron-capture detection.
AB  - One of the major processes that occur as a result of radical-induced oxidative
      stress is lipid peroxidation (LPO). Degradation of lipid peroxides results in
      various products, including a variety of carbonyl compounds. In the present study
      eight different lipid degradation products, i.e., formaldehyde, acetaldehyde,
      acetone, propanal, butanal, pentanal, hexanal and malondialdehyde were identified
      and measured simultaneously and quantitatively in rat urine after derivatization
      with O-(2,3,4,5,6-pentafluorbenzyl)hydroxylamine hydrochloride, extraction with
      heptane and using gas chromatography-electron-capture detection (GC-ECD). The
      identity of the respective oximes in urine was confirmed by gas chromatography
      negative ion chemical ionization mass spectrometry (GC-NCI-MS). Simultaneously
      measured standard curves were linear for all oxime-products and the detection
      limits were between 39.0 +/- 5.3 (n=9) and 500 +/- 23 (n=9) fmol per microl
      injected sample. Recoveries of all products from urine or water were 73.0 +/-
      5.2% and higher. In urine of CCl4-treated rats an increase in all eight lipid
      degradation products in urine was found 24 h following exposure. ACON showed the
      most distinct increase, followed by PROPA, BUTA and MDA. It is concluded that the
      rapid, selective and sensitive analytical method based on GC-ECD presented here
      is well suited for routine measurement of eight different lipid degradation
      products. These products appear to be useful as non-invasive biomarkers for in
      vivo oxidative stress induced in rats by CCl4.

PMID- 9252042
TI  - Analytical derivatizations of volatile and hydrophilic carbonyls from aqueous
      matrix onto a solid phase of a polystyrene-divinylbenzene macroreticular resin.
AB  - Extraction and derivatization of carbonyls to benzyloximes,
      pentafluorobenzyloximes or 2,4-dinitrophenylhydrazones is simplified and reaction
      times are substantially reduced by simultaneous sorption and derivatization from
      aqueous solution onto a solid phase. In this reaction a macroreticular
      polystyrene-divinylbenzene resin acts as a sorbent and catalyst to allow
      simultaneous extraction and derivatization of hydrophilic and lipophilic
      aldehydes and ketones from simple as well as complex matrices including plasma.
      Conversion to the 2,4-dinitrophenylhydrazones or pentafluorobenzyloximation at
      ambient temperature requires 10 and 20 min, respectively. These reaction
      conditions correspond to at least a 6-fold reduction in reaction times for
      derivatization of the reactive aldelhydes and a 36-72-fold reduction for
      preparation of derivatives for the slower reacting ketones.

PMID- 9252043
TI  - New antioxidant mixture for long term stability of serotonin, dopamine and their
      metabolites in automated microbore liquid chromatography with dual
      electrochemical detection.
AB  - An automated microbore liquid chromatographic assay with dual electrochemical
      detection is described for the determination of serotonin, dopamine and their
      metabolites, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and
      homovanillic acid. Due to the chemical instability of the compounds, the addition
      of an antioxidant is required for automated analysis over a long period of time
      (e.g., 20 h). Therefore, the time stability of these substances was tested with
      different antioxidants. The stability for serotonin and 5-hydroxyindoleacetic
      acid was poor in acidic medium containing Na2EDTA but could greatly be improved
      by the addition of L-cysteine and ascorbic acid. Using this assay, the
      neurotransmitters and their metabolites could easily be determined in
      microdialysates obtained from different rat brain areas.

PMID- 9252044
TI  - Study of salivary catecholamines using fully automated column-switching high
      performance liquid chromatography.
AB  - Cortisol and catecholamines are major physiological markers of human stress. In
      order to establish a fully automated assay system for both cortisol and
      catecholamines in saliva, which can be sampled without imposing stress, the
      previously developed system for salivary cortisol [Okumura et al., J. Chromatogr.
      B, 670 (1995) 11] was modified. The practical sensitivity was around 0.1 pmol ml(
      1) for norepinephrine and epinephrine and 0.5 pmol ml(-1) for dopamine. The
      established assay procedure provided R.S.D. values of 2 approximately 3% and
      recoveries of 96 approximately 104% at 0.5 pmol ml(-1). Measurement of salivary
      catecholamines in more than 300 samples taken from about 50 healthy volunteers
      indicated that the normal values of norepinephrine and dopamine were very low,
      about 0.1 pmol ml(-1) each. In contrast to cortisol, salivary catecholamine
      levels did not parallel those in plasma. Nevertheless, since levels of salivary
      catecholamines may reflect the sympathetic nerve activity in the salivary gland,
      they were assayed in volunteers making a scientific presentation before a large
      audience. Four out of eleven volunteers reported strong feelings of fear or
      anxiety, and their salivary catecholamine levels were about ten times higher than
      normal.

PMID- 9252045
TI  - Tyrosine hydroxylase assay for detection of low levels of enzyme activity in
      peripheral tissues.
AB  - A nonisotopic assay for tyrosine hydroxylase, with optimized signal-to-noise
      ratios, enables determination of low levels of enzyme activity in peripheral
      tissues. DOPA produced by the enzyme is measured using HPLC with electrochemical
      detection. Increased signal-to-noise ratios are obtained by including in the
      reaction mixture glycerol for reduction of blank values and dihydropteridine
      reductase and NADPH for regeneration of the tetrahydropteridine cofactor. With
      this method, tyrosine hydroxylase activity can be detected in as few as 200 PC12
      cells and in peripheral tissues at levels as low as 4.5 fmol/min/mg wet weight.
      The assay permits activity to be assessed in a variety of peripheral tissues.

PMID- 9252046
TI  - Simple high-performance liquid chromatographic method for assaying
      cysteinesulfinic acid decarboxylase activity in rat tissue.
AB  - A simple method is described for determining cysteinesulfinic acid decarboxylase
      activity in rat tissue. Enzyme preparations from the liver, kidney and brain were
      incubated with cysteinesulfinic acid substrate in the presence of pyridoxal 5
      phosphate. The enzyme product, hypotaurine, was derivatized with o-phthalaldehyde
      and separated by reversed-phase high-performance liquid chromatography (Capsel
      Pack AG 120A C18 column) using a mobile phase of acetonitrile-water (20:80, v/v)
      containing 50 mM sodium phosphate buffer (pH 6.0) and detected using a
      fluorometer (excitation at 360 nm and emission at 455 nm). The method described
      is reproducible and sensitive enough to determine the activity of
      cysteinesulfinic acid decarboxylase activity in the liver, kidney and brain. This
      assay was subsequently used to evaluate the effect of dietary proteins whose
      sulfur amino acid contents differ. Consistent with reported data, compared to
      casein and whole egg protein, a dietary protein low in sulfur amino acid (soybean
      protein) increased cysteinesulfinic acid decarboxylase activity in the liver and
      kidney. This method is therefore applicable to studies on the dietary regulation
      of cysteinesulfinic acid decarboxylase in rat tissue.

PMID- 9252047
TI  - In vivo determination of 5-bromo-2'-deoxyuridine incorporation into DNA tumor
      tissue by a new 32P-postlabelling thin-layer chromatographic method.
AB  - The halopyrimidine 5-bromo-2'-deoxyuridine (BUDR) can serve as one of many
      indicators of tumor malignity, complementary to histologic grade. We have
      developed a thin-layer chromatographic (TLC) technique that can assess tumor DNA
      base composition and analogue (BUDR) incorporation which vies with
      immunochemistry for BUDR. This requires post-labeling DNA by nick-translation and
      radioactive 5'-phosphorylation of representative 32P-alpha-dNMPs (deoxynucleotide
      monophosphates). Subsequent 3'-monophosphate digest exchanges a radioactive 32PO4
      for the neighboring cold nucleotide. Separation in two dimensional PEI-cellulose
      TLC is carried out in acetic acid, (NH4)2SO4, and (NH4)HSO4. TLC of dNMPs was
      applied to control HeLa DNA, and HeLa cells receiving BUDR. BUDR is detected in
      10(6) HeLa cells after 12-72 h incubations. Findings in HeLa DNA demonstrate
      normal TLC retention factors for all 32P-dNMPs. Two dimensional R(F) (x,y axes in
      cm) demonstrate: dAMP=1.4, 9.4; dCMP=10.0, 13.5; dGMP=4.6, 4.4; dTMP=9.0, 7.4;
      and BUDRMP 6.4, 6.6. This technique quantifies BUDR--which parallels tumor S
      phase, and serves as an indicator of labelling index (LI).

PMID- 9252048
TI  - Glutamate measured by 6-s resolution brain microdialysis: capillary
      electrophoretic and laser-induced fluorescence detection application.
AB  - In the present experiment the combination of brain microdialysis and CZE-LIFD
      permitted the measurement of glutamate in 100 nl microdialysis samples collected
      every 5 or 6 s. Samples were collected every 6 s, in rats anesthetized with two
      different anesthetic agents (ketamine and sodium thiopental). A microdialysis
      probe was inserted in the cortex of an anesthetized rat in the territory
      irrigated by the middle cerebral artery. The artery was clamped for 30 s and then
      released. The samples were derivatized with fluorescein isothiocyanate I (FITC)
      by means of a continuous-flow reactor, collected and injected into a home-made
      CZE-LIFD instrument. Glutamate decreased immediately after clamping the artery in
      ketamine anesthetized rats and increased 1 min after the onset of the ischemia in
      sodium thiopental anesthetized rats. In another experiment a 60 mM KCl solution
      was injected through a microdialysis probe inserted in the hippocampus of an
      anesthetized rat. In the first 5 s after the KCl solution reached the tissue,
      glutamate increased but gamma-aminobutytic acid and glutamine did not. The
      experiments show that time resolution of brain microdialysis can be reduced to a
      few seconds if the analytical technique is the proper one.

PMID- 9252049
TI  - Determination of 5-hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide
      in human urine.
AB  - A method for simultaneous determination of 5-hydroxy-N-methylpyrrolidone and 2
      hydroxy-N-methylsuccinimide in urine is described. These compounds are
      metabolites of N-methyl-2-pyrrolidone, a powerful and widely used organic
      solvent. 5-Hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide were
      purified from urine by adsorption to a C8 solid-phase extraction column and then
      elution by ethyl acetate-methanol (80:20). After evaporation, the samples were
      derivatised at 100 degrees C for 1 h by bis(trimethylsilyl)trifluoroacetamide.
      Ethyl acetate was then added and the samples were analysed by gas chromatography
      mass spectrometry in the electron impact mode. The extraction recovery for 5
      hydroxy-N-methylpyrrolidone was about 80% while that for 2-hydroxy-N
      methylsuccinimide was about 30%. The intra-day precision for 5-hydroxy-N
      methylpyrrolidone was 2-4% and the between-day precision 4-21% (4 and 60
      microg/ml). The intra-day precision for 2-hydroxy-N-methylsuccinimide was 4-8%
      and the between-day precision 6-7% (2 and 20 microg/ml). The detection limit was
      0.2 microg/ml urine for both compounds. The method is applicable for analysis of
      urine samples from workers exposed to N-methyl-2-pyrrolidone.

PMID- 9252050
TI  - Measurement of synthetic phenolic antioxidants in human tissues by high
      performance liquid chromatography with coulometric electrochemical detection.
AB  - The antioxidants, 2-tert.-butyl-4-methoxyphenol (BHA) and its oxidative
      peroxidation product 2,2'-dihydroxy-3,3'-di-tert.-butyl-5,5'-dimethoxybiphenyl
      (di-BHA), 3,5-di-tert.-butyl-4-hydroxytoluene (BHT) and propyl gallate, were
      measured in plasma and tissue homogenates by HPLC and electrochemical detection,
      with a sensitivity down to 0.2 (BHA), 0.1 (di-BHA), 0.4 (BHT) and 1 (propyl
      gallate) ng ml(-1) of plasma or tissue homogenate. The data demonstrate that in
      man, at the current level of exposure to dietary antioxidants, significant
      amounts of BHA, BHT and propyl gallate are accumulated in the omentum.
      Furthermore, they provide the first evidence that the peroxidase-catalysed
      oxidation of BHA is operative in man.

PMID- 9252051
TI  - Analysis of some metabolites of organic solvents in urine by high-performance
      liquid chromatography with beta-cyclodextrin.
AB  - Chromatographic separation of the metabolites derived from toluene, ethylbenzene,
      styrene and xylene was carried out on untreated urine samples from factory
      workers. The elution sequence was as follows: phenylglyoxilic acid, 3-hydroxy-2
      butanone, hippuric acid, o-methylhippuric acid, p-methylhippuric acid, m
      methylhippuric acid, p-cresol, m-cresol and o-cresol. The stability constants
      (K(G)) of cresol and methylhippuric acid derivatives were evaluated. The capacity
      factor (k'), selectivity factor (alpha) and resolution (Rs) are described with a
      variety of mobile phases containing beta-cyclodextrin (beta-CD). The optimum
      concentration ratio of ethanol-water-acetic acid-beta-CD was determined to be
      20:80:0.3:1.4%. Under these conditions, k' values of the five metabolites were
      2<k'<6, and all alpha values were greater than 1.5. Simultaneous determinations
      of the metabolites were carried out in real urine samples from factory workers
      using the standard addition method. Validation of the method and the detection
      limit are described under the optimum conditions attained in this experiment.

PMID- 9252052
TI  - Determination of psilocybin in Psilocybe semilanceata by capillary zone
      electrophoresis.
AB  - A capillary zone electrophoretic (CZE) method was developed for the rapid
      determination of psilocybin in Psilocybe semilanceata. Following a simple two
      step extraction with 3.0+2.0 ml methanol, the hallucinogenic compound was
      effectively separated from matrix components by CZE utilizing a 10 mM borate
      phosphate running buffer adjusted to pH 11.5. The identity of psilocybin was
      confirmed by migration time information and by UV spectra, while quantitation was
      accomplished utilizing barbital as internal standard. The calibration curve for
      psilocybin was linear within 0.01-1 mg/ml, while intra-day and inter-day
      variations of quantitative data were 0.5 and 2.5% R.S.D., respectively. In
      addition to psilocybin, the method was also suitable for the determination of the
      structurally related compound baeocystin.

PMID- 9252053
TI  - Simultaneous determination of six penicillins in cows' raw milk by a multiresidue
      high-performance liquid chromatographic method.
AB  - A high-performance liquid chromatographic method based on C18 solid-phase
      extraction and ultraviolet detection at 323 nm of analytes derivatized with
      benzoic anhydride and 1,2,4-triazole mercuric chloride solution was developed for
      the simultaneous determination of amoxicillin, penicillin G (benzylpenicillin),
      ampicillin, oxacillin, cloxacillin and dicloxacillin residues in raw milk. The
      detection limit of the method was 1.3 microg/l for penicillin G; 1.4 microg/l for
      amoxicillin, oxacillin and cloxacillin, 1.5 microg/l for ampicillin and 2.7
      microg/l for dicloxacillin. The mean recovery was 95-102% for amoxicillin,
      penicillin G and ampicillin, 92-98% for oxacillin and cloxacillin and 87-94% for
      dicloxacillin, measured by using an internal standard. The relative repeatability
      standard deviation was 4-9% on level 4-15 micro/l, respectively, 2-7% on level 30
      40 microg/l.

PMID- 9252054
TI  - Determination of erythromycin in urine and plasma using microbore liquid
      chromatography with tris(2,2'-bipyridyl)ruthenium(II) electrogenerated
      chemiluminescence detection.
AB  - Erythromycin is determined in both urine and plasma samples using microbore
      reversed-phase liquid chromatography with tris(2,2'-bipyridyl)ruthenium(II)
      [Ru(bpy)3(2+)] electrogenerated chemiluminescence (ECL) detection. Ru(bpy)3(2+)
      is included in the mobile phase thus eliminating band broadening caused by post
      column reagent addition. Extra column band broadening is an important concern in
      microbore liquid chromatography due to the small peak volumes. Erythromycin was
      studied in both water and biological samples. The detection limit for
      erythromycin in standards is 0.01 microM or 50 fmol injected with a S/N of 3 and
      a linear working range that extends four orders of magnitude. Human urine and
      blood plasma were also studied. Urine samples were diluted and filtered before
      injection. Ultrafiltration was used to remove protein from blood plasma samples
      prior to injection. Erythromycin was selectively detected in the body fluid
      samples without any further sample preparation. The detection limits obtained for
      erythromycin in urine and plasma are 0.05 and 0.1 microM, respectively, for 5
      microl injected on a 150x1 mm I.D. C18 column.

PMID- 9252055
TI  - Rapid method for the determination of ampicillin residues in animal muscle
      tissues by high-performance liquid chromatography with fluorescence detection.
AB  - A rapid and sensitive HPLC method was developed for the determination of
      ampicillin residues in muscle tissues of beef, pork, chicken and catfish. Muscle
      tissues were blended with a food processor into paste. A 5-g aliquot of the
      blended tissues was homogenized with 14 ml of 0.01 M phosphate buffer (pH 4.5)
      using a tissue homogenizer. Proteins were precipitated with the addition of 1 ml
      trichloroacetic acid (75%, w/v) followed by centrifugation. After filtration, 1
      ml of the supernatant was reacted with formaldehyde under acidic and heating
      conditions. The ampicillin fluorescent derivative was then analyzed by reverse
      phase HPLC with fluorescence detection. Recoveries of spiked ampicillin at 5, 10
      and 20 ng/g were >85%, with coefficients of variation <5%. The limit of detection
      and limit of quantitation for ampicillin in the tissues were 0.6 ng/g and 1.5
      ng/g, respectively. The method is also applicable to the analysis of ampicillin
      residue in dry milk powder.

PMID- 9252056
TI  - Rapid and simple method for the determination of zolpidem in human plasma by high
      performance liquid chromatography.
AB  - A simple and reproducible method for the determination of zolpidem in human
      plasma is presented. This method involves protein precipitation with methanol (2
      ml of methanol are added to 0.5 ml of plasma) and reversed-phase chromatography
      with fluorescence detection (excitation wavelength 244 nm, emission wavelength
      388 nm). The mobile phase consists of methanol-30 mM dihydrogen potassium
      phosphate-triethylamine (30:69:1). pH of the aqueous part of the mobile phase is
      6.8. No internal standard is required. Limit of quantitation is 1.5 ng/ml and the
      calibration curve is linear up to 400 ng/ml. Within-day and between-day precision
      expressed by relative standard deviation is less than 5% and inaccuracy also does
      not exceed 9%. The assay is useful for pharmacokinetic studies.

PMID- 9252057
TI  - High-performance liquid chromatographic assay of bromocriptine in plasma and eye
      tissue of the rabbit.
AB  - A reliable reversed-phase high-performance liquid chromatographic method has been
      developed for the determination of bromocriptine (BCT) in plasma and eye tissues.
      The BCT and propranolol, added as an internal standard (I.S.), were extracted by
      a liquid-liquid technique followed by an aqueous back-extraction, allowing
      injection of an aqueous solvent into a 4-microm Nova-Pak C18 column (150x3.9 mm
      I.D.). The mobile phase was a mixture of 30 parts of acetonitrile and 70 parts of
      0.2% triethylamine (pH 3) at a flow-rate of 1 ml/min. Fluorescence detection was
      at an excitation wavelength of 330 nm and an emission wavelength of 405 nm. The
      retention times of I.S. and BCT were 4.1 and 11.6 min, respectively. The
      calibration curve was linear over the concentration range 0.2-10 microg/l for
      plasma (r>0.999) and vitreous humour (r>0.997) and 1-50 microg/l for aqueous
      humour (r>0.985). The limit of quantification was 0.2 microg/l for plasma and
      vitreous humour using a 1-ml sample and was 1 microg/l for aqueous humour using a
      0.2-ml sample. The quality control samples were reproducible with acceptable
      accuracy and precision. The within-day recovery (n=3) was 100-102% for plasma, 91
      106% for aqueous humour and 96-111% for vitreous humour. The between-day recovery
      (n=9) was 90-114% for plasma, 83-115% for aqueous humour and 90-105% for vitreous
      humour. The within-day precision (n=3) and the between-day precision (n=9) were
      1.7-7.0% and 8.1-13.6%, respectively. No interferences from endogenous substances
      were observed. Taken together, the above simple, sensitive and reproducible high
      performance liquid chromatography assay method was suitable for the determination
      of BCT in plasma and eye tissues following ocular application of BCT for the
      therapy of myopia.

PMID- 9252058
TI  - Partition coefficients (n-octanol/water) of N-butyl-p-aminobenzoate and other
      local anesthetics measured by reversed-phase high-performance liquid
      chromatography.
AB  - For the determination of the logarithmic partition coefficients between n-octanol
      and water (log P(o/w)) of local anesthetics, the pH of the aqueous phase needs to
      be adjusted to high values to ensure that the local anesthetics are in the
      unionized form. Using the shake-flask or the stir-flask method, this high pH may
      catalyze hydrolysis, leading to increasing amounts of impurities in time. These
      impurities exclude non-selective quantification methods like UV spectrometry and
      require repetitive quantitative analysis of both liquid phases resulting in a
      tedious and time-consuming method. A rapid reversed-phase HPLC method was
      developed to measure log P(o/w) of the local anesthetics N-butyl-p-aminobenzoate,
      methyl-p-aminobenzoate, benzocaine, procaine, mepivacaine, prilocaine, lidocaine,
      bupivacaine, etidocaine, tetracaine and oxubuprocaine.

PMID- 9252059
TI  - Determination of saquinavir in human plasma by high-performance liquid
      chromatography.
AB  - We developed and characterized a high-performance liquid chromatography (HPLC)
      assay for the determination of saquinavir, an HIV protease inhibitor, in human
      plasma samples. Extraction of plasma samples with diethyl ether resulted in
      quantitative recovery of both saquinavir and its stereoisomer Ro 31-8533 which
      was used as an internal standard. The assay was performed isocratically using 5
      mM H2SO4 (pH 3.5) and acetonitrile (75.5:24.5, v/v) containing 10 mM
      tetrabutylammonium hydrogen sulfate (TBA) as a mobile phase, a Nucleosil 3C8
      column kept at 45 degrees C and UV detection at 240 nm. Using this method,
      saquinavir and Ro 31-8533 can be separated from endogenous substances, and in the
      concentration range of 5-110 ng/ml the relative standard deviations for the
      determination of saquinavir were below 5%. The detection limit of saquinavir in
      human plasma was 1 ng/ml. The usefulness of the method was demonstrated by
      quantification of saquinavir in plasma of human subjects treated with 600 mg of
      saquinavir per os or 12 mg intravenously.

PMID- 9252060
TI  - Determination of the lactone and lactone plus carboxylate forms of 9
      aminocamptothecin in human plasma by sensitive high-performance liquid
      chromatography with fluorescence detection.
AB  - Two sensitive reversed-phase high-performance liquid chromatographic fluorescence
      methods, with simple sample handling at the site of the patient, are described
      for the determination of the lactone and lactone plus carboxylate forms of 9
      aminocamptothecin (9AC). For 9AC lactone, the sample preparation was a liquid
      liquid extraction with acetonitrile-n-butyl chloride (1:4, v/v), whereas the
      sample preparation for 9AC total (lactone plus carboxylate) was a simple
      deproteinization with 5% perchloric acid-methanol (1:1, v/v), which results in
      the conversion of the carboxylate into the lactone form. The lower limits of
      quantitation were 50 pg/ml and 100 pg/ml for 9AC lactone and 9AC total,
      respectively. The within-run precisions at four tested concentrations were < or =
      6.3% for 9AC lactone and < or = 5.3% for 9AC total. The between-run precisions
      were < or = 8.9% and < or = 5.6%, respectively. The assays were developed to
      enable pharmacological analysis of 9AC in a bioavailability and oral phase I
      study in patients with solid tumors.

PMID- 9252061
TI  - Fluorodensitometric evaluation of gentamicin from plasma and urine by high
      performance thin-layer chromatography.
AB  - High-performance thin-layer chromatographic (HPTLC) analysis of gentamicin by in
      situ fluorodensitometric evaluation of its 4-chloro-7-nitrobenzo-2-oxa-1,3
      diazole (NBD-Cl) derivative is presented. The aminoglycoside components separated
      on silica gel plates using chloroform-methanol-20% ammonium hydroxide
      (2.4:2.2:1.5, v/v/v) as the mobile phase were reacted with NB-Cl to yield highly
      fluorescent derivatives. The calibration curves of gentamicin in water, plasma
      and urine were linear in the range 40-200 ng. The mean values of intercept, slope
      and correlation coefficient were 16.82 +/- 0.473, 6.83 +/- 0.015 and 0.9968 +/-
      0.0017 for standard curves in water, 17.35 +/- 0.375, 6.85 +/- 0.018 and 0.9941
      +/- 0.0012 for standard curves in plasma and 14.35 +/- 0.286, 6.86 +/- 0.002 and
      0.9933 +/- 0.0011 for standard curves in urine respectively. The analytical
      technique was validated for within-day and day-to-day variation. The results
      indicate that HPTLC, coupled with in situ fluorodensitometry, is a reliable and
      valuable technique for quantitative analysis of the bulk drug gentamicin and
      gentamicin from urine and plasma.

PMID- 9252062
TI  - High-performance thin-layer chromatographic determination of flurbiprofen in
      plasma.
AB  - A high-performance thin-layer chromatographic (HPTLC) method for the assay of
      flurbiprofen in plasma is reported. The drug was extracted from acidified plasma
      with hexane-diethyl ether (80:20). The mobile phase composition was n-hexane
      ethyl acetate-glacial acetic acid (60:30:10). Densitometric analysis of
      flurbiprofen was carried out at 247 nm. The calibration curves of flurbiprofen in
      methanol and in plasma were linear in the range 40-400 ng. The mean values of
      correlation coefficient, slope and intercept were 0.995 +/- 0.003, 0.075 +/-
      0.002 and 4.39 +/- 0.05 for standard curves in methanol and 0.992 +/- 0.002,
      0.066 +/- 0.007 and 3.40 +/- 0.72 for standard curves in plasma, respectively.
      The limit of quantitation for flurbiprofen in human plasma was 40 ng, and no
      interference was found from endogenous compounds. The recovery of flurbiprofen
      from human plasma using the described extraction procedure was about 87%. The
      coefficient of variation for within-day and between-day analyses was 2.53% and
      3.96% for 200 ng and 1.76% and 2.30% for 400 ng flurbiprofen concentration,
      respectively. The method was utilized to monitor plasma concentration of
      flurbiprofen post administration of sustained release capsules in human patient
      volunteers.

PMID- 9252063
TI  - Improved method for the measurement of glutamate and aspartate using capillary
      electrophoresis with laser induced fluorescence detection and its application to
      brain microdialysis.
AB  - We have previously published data on the analysis of glutamate in microdialysis
      samples using a commercially available CE apparatus. Here we demonstrate further
      improvements in the analysis of both glutamate and aspartate from very small
      volume microdialysates. The limit of detection of our system has been increased
      to 10(-9) M for both glutamate and aspartate. This permits microdialysis sampling
      time to be reduced to 2 min, thus improving the temporal resolution of
      microdialysis sampling. Concurrently, migration time has also been reduced such
      that resolution of both amino acids can be achieved inside 2 min. This new
      analytical method has been applied to the measurement of the EAA from
      microdialysis samples from the dentate gyrus of the hippocampus. Extracellular
      concentrations of both glutamate and aspartate increased to a maximum of 5- and
      4.5-fold of preinfusion values, respectively, during infusion of 100 mM K+
      through the microdialysis probe. This is consistent with the depolarization
      evoked release of both amino acids from this brain region.

PMID- 9252064
TI  - Identification and quantitative determination of uric acid in human urine and
      plasma by capillary electrophoresis with amperometric detection.
AB  - Application of capillary zone electrophoresis with electrochemical detection to
      the identification and quantitative determination of uric acid in human urine as
      well as plasma is described. This work was carried out in a 30 cm x 25 microm
      I.D. fused-silica capillary with tricine buffer and a carbon fiber bundle was
      employed as a working electrode, the working voltage in amperometric detection
      was set at +0.80 V (vs. SCE). The sample constituent is identified by stopped
      flow-linear sweep voltammetry. Under optimal conditions, a lower detection limit
      of 0.48 fmol was obtained for uric acid.

PMID- 9252065
TI  - Determination of eltanolone in human plasma by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic method for the determination of
      eltanolone in plasma has been developed. Plasma samples containing eltanolone
      were diluted with acetonitrile to precipitate plasma proteins, and derivatized
      with 2,4-dinitrophenylhydrazine before direct injection onto a C18 column. The
      mobile phase was acetonitrile-water (70:30, v/v) containing 0.1% trifluoroacetic
      acid and detection was by UV absorbance at 367 nm. The quantitation limit was
      0.020 microg/ml. The method has proven to be rapid, precise and sensitive in the
      range of concentrations found during and following intravenous anaesthesia.

PMID- 9252066
TI  - Persistent unconjugated hyperbilirubinemia after liver transplantation due to an
      abnormal bilirubin UDP-glucuronosyltransferase gene promoter sequence in the
      donor.
AB  - BACKGROUND/AIMS: Gilbert's syndrome is genetically characterized by an extra TA
      element in the TATAA-box of the promotor region upstream of the bilirubin UDP
      glucuronosyltransferase (UGT1A) coding region (Bosma et al. N Engl J Med 1995;
      333: 1171-5). Persistent unconjugated hyperbilirubinemia is occasionally observed
      in liver transplant recipients with an otherwise normal liver function. We
      postulate that these patients could have received a liver from a donor with the
      Gilbert's syndrome genotype. Therefore, we investigated the UGT1A-gene TATAA-box
      in DNA from liver graft donors of jaundiced and non-jaundiced recipients.
      METHODS: DNA was obtained from stored donor lymphocytes and the number of TA
      elements in the TATAA-box of the UGT1A-gene promotor region was analyzed by
      polymerase chain-reaction. RESULTS: We observed two liver transplant recipients
      with persistent unconjugated hyperbilirubinemia. They received liver grafts from
      donors who were homozygous for an abnormal A(TA)7TAA-box in the UGT1A-gene. Four
      of 10 non-jaundiced recipients received livers from donors who were homozygous
      for the normal A(TA)6TAA-box and six received livers from donors who were
      heterozygous with a normal A(TA)6TAA-box on one allele and a prolonged A(TA)7TAA
      box on the other allele. CONCLUSIONS: This study shows that liver graft
      recipients with persistent unconjugated hyperbilirubinemia may have received a
      liver from a donor with an abnormal TATAA-box in the bilirubin UGT1A-gene
      promotor region.

PMID- 9252067
TI  - Interleukin-1-producing plasma cells in close contact with hepatocytes in
      patients with chronic active hepatitis.
AB  - BACKGROUND/AIMS: In chronic active liver diseases (CALD) with viral aetiology, a
      population of plasma cells localised in the piecemeal necrosis areas was
      previously detected by means of autoradiography after in vitro 3H-proline
      incorporation, a method which proved much more sensitive than conventional
      immunohistochemical procedures. These plasma cells, characteristically located in
      niches among hepatocytes, in close contact with collagen fibrils, have been
      hypothesised to exert a role in fibrogenesis stimulation, and particularly in
      collagen synthesis, possibly through secretion of lymphokines. Specifically, we
      investigated the presence of interleukin-1, well known to play a crucial role in
      inflammation and production of collagen by epithelial cells, and to be present in
      activated plasma cells of myeloma. METHODS: The immunohistochemical localisation
      of interleukin-1beta in biopsies of patients suffering from chronic active
      hepatitis was studied, using an affinity-purified rabbit polyclonal antibody.
      RESULTS: The strongest interleukin-1beta immunostaining was observed in the above
      described plasma cell population, identified by anti-immunoglobulin antibodies,
      and 3H-proline incorporation. CONCLUSIONS: The ability of plasma cells to produce
      interleukin-1 during viral CALD suggests that in these pathologies plasma cells
      play a major role, mainly of paracrine nature. Interleukin-1, possibly together
      with other mediators, might in turn stimulate the production of collagen.
      Hepatocytes of the piecemeal necrosis area appear to be possible candidates for
      this synthesis, as they show a significant labelling after 3H-proline
      incorporation, which is absent from hepatocytes far from necrotic areas.

PMID- 9252068
TI  - Hepatitis B and C in HIV-infected patients. Prevalence and prognostic value.
AB  - BACKGROUND/AIMS: There is only limited information on the prevalence and
      influence of coinfection with either hepatitis B or C on the clinical course in
      patients infected with the human immunodeficiency virus (HIV). METHODS: Follow-up
      was available in 232 HIV-infected patients (age 37+/-8 years, CD4 count 167+/-167
      microl; 46% had AIDS). Samples were investigated for markers of HBV and HCV
      infection (HBsAg, HBeAg, HBV-DNA, Anti-HBs, anti-HBc, anti-HCV, HCV-RNA).
      RESULTS: 60/232 patients (23%) were anti-HCV positive. 78% of these sera were
      positive for HCV-RNA. 22/232 patients (9%) suffered from chronic HBV infection
      (HBsAg positive), 18/22 (82%) of these sera had detectable HBeAg and 19/22 (86%)
      HBV-DNA. Presence of HCV-RNA, HBeAg and amount of HBV-DNA were related to the
      degree of immunodeficiency. In contrast to the control group without HBV or HCV
      infection, patients infected with HIV and either HBV or HCV showed a direct
      correlation between a reduction in CD4 counts and decreased cholinesterase
      activity. In patients with AIDS, coinfection with HBV or HCV was associated with
      a reduced survival compared to controls (HBV: 212 days, 95%CI, 106-317; HCV: 267,
      95%CI, 112-396; controls: 439 days, 95%CI, 364-513). CONCLUSIONS: Coinfection of
      HIV and HBV or HCV is frequently observed. Our results suggest that with
      prolonged survival of HIV-infected patients, coinfection with either HBV or HCV
      correlates with a reduced survival rate.

PMID- 9252069
TI  - Unexpected high prevalence of hepatitis C virus genotype 4 in Southern Spain.
AB  - BACKGROUND/AIMS: A unusually high rate of HCV-infected individuals in whom the
      HCV genotype cannot be ascertained by means of single PCR and LIPA procedures has
      recently been reported in our area. The aim of the present study was to
      investigate the epidemiological, clinical and molecular characteristics of these
      patients. METHODS: Cross-sectional study. Eighty anti-HCV-positive patients with
      chronic liver disease, 45 (56.25%) of them intravenous drug users, were included.
      HCV genotyping was carried out in all patients using commercial single PCR and
      LIPA procedures. Samples where no HCV RNA amplification and/or indeterminate HCV
      genotype were found were also tested by means of a nested PCR. HCV viral load was
      measured in all patients. RESULTS: HCV genotyping was not achieved in 23 (28.75%)
      individuals. No amplification of HCV RNA was found in 19 of them, and in four
      other cases the LIPA procedure did not allow identification of a distinct HCV
      genotype. After the use of nested PCR+LIPA, it was found that the HCV genotype 4
      was found in 11 of those 23 individuals (47.82%). Ten of these 11 HCV genotype 4
      harboring individuals were intravenous drug users. The HCV viral load was lower
      in HCV genotype 4-harboring individuals than in those whom the genotypes 1, 2 or
      3 were found (p<0.001). CONCLUSIONS: A high rate of HCV genotype 4-harboring
      cases has been found among HCV-infected individuals in Southern Spain. Had only
      single PCR been used, these individuals could have been wrongly regarded as non
      viremic.

PMID- 9252070
TI  - Epidemiology of hepatitis C virus infection in an area of Southern Italy.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) has been recognized as a major cause of
      liver disease, but little is known about its diffusion at population level. To
      estimate the prevalence and incidence of HCV infection and to explore potential
      risk factors at population level, an epidemiologic study was carried out.
      METHODS: A cohort was built up in 1985, on a random sample of the population of
      Castellana, a small town in southern Italy (Bari province), and followed up until
      1993. HCV ELISA II and RIBA HCV 2.0 were used as screening and confirmatory
      tests, respectively. RESULTS: The overall anti-HCV prevalence was 26.0%
      (511/1969) at enrollment. The HCV infection incidence rate was 34.2x100,000
      person-years (3 cases/8766 persons-years). A secular trend (referent born before
      1930; born 1930-39 Odds Ratio (OR) 0.72, 95% Confidence Interval (95% CI) 0.56
      0.94; born 1940-49, OR 0.33, 95% CI 0.25-0.44; born 1950 or after, OR 0.15, 95%
      CI 0.09-0.23) and geographical pattern (referent born outside Bari province; born
      in Bari province, OR 1.71, 95% CI 0.93-3.16; born in Castellana G, OR 2.29, 95%
      CI 1.29-4.05) were found by logistic regression analysis after controlling for
      several confounding factors. CONCLUSIONS: The high prevalence, moderate
      incidence, and marked decrease in HCV infection in the cohort of birth in a
      population without known risk factors suggest that an epidemiological transition
      has been operating at population level since the 1950's.

PMID- 9252071
TI  - Significance of IgM anti-HCV core level in chronic hepatitis C.
AB  - AIM: To investigate the significance of IgM antibody to hepatitis C virus (HCV)
      core antigen (IgM anti-HCV core) in chronic hepatitis C. METHODS: In a group of
      112 patients with histologically proven chronic hepatitis C positive for HCV RNA,
      IgM anti-HCV core level was studied by a sensitive semi-quantitative enzyme
      immunoassay. Quantitation of serum HCV RNA was done by a second generation bDNA
      assay and determination of HCV genotype by RT-PCR and reverse hybridization.
      RESULTS: IgM anti-HCV core was detected in 72 (64.3%) of the 112 patients. ALT
      levels were significantly higher in IgM anti-HCV core positive than negative
      patients. No other significant difference was observed in any of the patients'
      characteristics between IgM anti-HCV core positive and negative groups. On the
      contrary, IgM anti-HCV core level was found to be significantly higher in females
      than in males, in patients with moderate or severe chronic hepatitis, in patients
      with high HCV RNA levels and in patients infected with HCV genotype 1b. Moreover,
      IgM anti-HCV core level was significantly correlated with age and ALT level.
      Multiple regression analysis showed that IgM anti-HCV core level was
      significantly related only to the HCV genotype (p=0.001), histological grade
      (p=0.017) and ALT level (p=0.038). CONCLUSIONS: Our data support the hypothesis
      that IgM anti-HCV core level is associated mainly with HCV genotype and secondly
      with liver disease necroinflammatory activity. These associations may have
      implications in the pathogenesis of chronic hepatitis C.

PMID- 9252072
TI  - Serine protease inhibitors in patients with chronic viral hepatitis.
AB  - BACKGROUND/AIMS: This study aimed to determine whether deficiency of the major
      serine protease inhibitors (alpha1-antitrypsin (AAT) or alpha1-antichymotrypsin
      (ACT)) is associated with increased risk for chronic hepatitis B or C virus (HBV
      or HCV) infection. METHODS: We studied 709 adults with chronic liver disease who
      had undergone liver biopsy during the 14-year period 1978-92. Anti-HCV testing
      was carried out with second-generation ELISA and immunoblot assays (RIBA 2). HBV
      markers were tested with commercially available radioimmunoassays. ACT and AAT
      concentrations in plasma were measured with electroimmunoassay and immune
      nephelometry. Plasma samples were screened for the AAT PiZ deficiency with ELISA
      technique and phenotyped by isoelectric focusing. The 229Pro-->Ala mutation for
      ACT deficiency was identified by PCR techniques. RESULTS: Of the 709 patients,
      132 (18.6%) were positive for anti-HCV according to RIBA 2. PiZ AAT deficiency
      was found in 44 (6.2%) of patients (one PiZZ, 38 PiMZ, and PiSZ), while subnormal
      ACT levels were found in 33 (4.6%) patients, frequencies that were higher than
      expected in the general population (p=0.0375 and p<0.0001, respectively). Of the
      PiZ-carriers, 8/44 (18%) were found to be anti-HCV positive according to RIBA 2,
      as compared to 123/662 (19%) non-PiZ-carriers (p>0.05). One of these patients had
      cirrhosis, four chronic active hepatitis, and three chronic persistent hepatitis.
      In contrast, 17/33 (51.5%) of the patients with subnormal ACT were anti-HCV
      positive (OR=5.2, CI=2.6-10.6; p<0.0001). No relationship was found between HBV
      infection and AAT deficiency or subnormal ACT levels. Only one patient with
      subnormal ACT levels was heterozygous for the 229Pro-->Ala mutation of ACT
      deficiency. There was no significant difference in the histological findings when
      the patients with subnormal ACT levels or PiZ allele were subgrouped according to
      HCV status. CONCLUSIONS: There is no overrepresentation of chronic HBV or HCV in
      heterozygous AAT deficiency, although an association with more severe liver
      disease in such patients cannot be excluded. In contrast, low plasma levels of
      ACT that may be acquired or hereditary, due to mutations other than 229Pro-->Ala,
      are frequent in HCV infection.

PMID- 9252073
TI  - Time course of histological changes in patients with a sustained biochemical and
      virological response to interferon-alpha therapy for chronic hepatitis C virus
      infection.
AB  - BACKGROUND/AIMS: Although biochemical and virological responses to interferon
      alpha therapy for chronic hepatitis C virus infection have been extensively
      studied, long-term changes in liver histology have not been well documented.
      METHODS: We retrospectively analyzed 105 paired liver biopsy specimens taken
      before and after treatment from 93 patients who persistently showed biochemical
      remission and an absence of viremia for up to 68 months. RESULTS: The grading
      scores for necroinflammatory and fibrotic activity in the liver biopsy specimens
      decreased significantly after interferon-alpha therapy. Histological scores
      graded according to Knodell's components improved significantly in every category
      after interferon-alpha therapy. However, inflammatory cell infiltrates remained
      within the portal tracts for long periods; necroinflammation in the periportal
      and lobular regions were absent in most of the post-therapy specimens. The
      cumulative disappearance rate, calculated using the Kaplan-Meier method, was
      significantly lower for portal inflammation than for periportal or lobular
      necroinflammation but was equivalent to that for histological disease activity.
      On univariate analysis, age and fibrosis at the onset of treatment were
      significant factors influencing the response of histological disease activity to
      interferon-alpha therapy (p=0.025 and 0.049, respectively). Using Cox's
      proportional hazard analysis, age was the only significant independent predictor
      of histological response to treatment (p=0.035). CONCLUSIONS: Clinical remission
      of chronic hepatitis C virus infection is associated with histological resolution
      of necroinflammation in the periportal and lobular regions. Host-related factors
      are likely to influence whether early remission of inflammation after interferon
      alpha therapy occurs.

PMID- 9252074
TI  - Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon
      alpha-2b for chronic hepatitis type C. Results of a multicenter randomized trial.
AB  - BACKGROUND/AIMS: To examine the effect of prolonged treatment with different
      doses of interferon alpha-2b on the relapse rate in patients with chronic
      hepatitis C. METHODS: One hundred and seventy-one patients with non-cirrhotic
      chronic hepatitis C were enrolled in an Italian multicenter trial. All patients
      were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b
      given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine
      aminotransferase (ALT) values were given 6 MU of interferon for an additional 3
      months. If ALT remained persistently abnormal, therapy was then suspended. If ALT
      levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18
      months (total=2 years). Patients with normal ALT were randomly assigned to two
      groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional
      21 months (total=2 years). Follow-up continued for 2 years after therapy
      withdrawal. RESULTS: Seven patients stopped treatment during the first 3 months.
      Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months
      of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a
      sustained response was maintained in eight during the follow-up. Overall, 54 and
      34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU
      long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and
      21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.).
      After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21
      (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to
      treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT
      values, HCV-RNA negative). About 65% of the sustained responders showed low
      baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b
      was more frequently found among non-responders than in long-term responders (84%
      vs 25%, p=0.0001). CONCLUSIONS: About 14% of patients who do not respond to a 3
      month course of 3 MU of interferon normalize ALT levels when given 6 MU. In
      prolonged treatment, there is no significant difference between 3 and 6 MU in
      inducing a sustained response. Patients with low baseline viremia and genotype 2a
      respond significantly better to prolonged interferon therapy than highly viremic
      patients with genotype 1b.

PMID- 9252075
TI  - Interferon-alpha treatment of hepatitis C virus-associated mixed
      cryoglobulinemia.
AB  - BACKGROUND/AIMS: Chronic hepatitis C virus infection is frequently associated
      with mixed cryoglobulinemia. The efficacy of interferon-alpha treatment in the
      presence of cryoglobulinemia, particularly the rate of sustained responders, has
      not yet been well defined. METHODS: Fifty-nine consecutive patients with chronic
      HCV infection were studied prospectively with regard to the presence of
      cryoglobulinemia and their biochemical and virological response to interferon
      alpha2a therapy. RESULTS: Cryoglobulins were detected in sera of 23 patients. For
      this latter group of patients, significant differences were found compared to the
      36 patients without cryoglobulinemia, i.e. the prevalence of female sex was
      higher, the duration of liver disease was longer and distinctive laboratory
      abnormalities, e.g. higher rheumatoid factor activity, were noted as well as a
      higher prevalence of cirrhosis. The distribution of HCV genotypes and serum HCV
      RNA titers was similar in the two groups. Interferon-alpha treatment regimens
      were not different regarding mean cumulative dose and mean duration of therapy.
      The response to therapy was almost identical, i.e. 35% of patients with
      cryoglobulinemia showed a sustained response compared to 22% of patients without
      cryoglobulinemia. The percentages of patients showing a relapse or breakthrough
      were similar in both groups. Pre-treatment viremia levels were higher in non
      responders compared to sustained responders. Non-responders appeared to be more
      frequent among patients infected with genotypes 1a and 1b, especially among male
      patients without cryoglobulinemia. CONCLUSIONS: The presence of cryoglobulinemia
      per se in chronic HCV-infected patients does not adversely affect the outcome of
      interferon-alpha therapy, including the rate of sustained response.

PMID- 9252077
TI  - Cleavage of viral RNA and inhibition of viral translation by hepatitis C virus
      RNA-specific hammerhead ribozyme in vitro.
AB  - BACKGROUND/AIMS: A hammerhead ribozyme has been used as a new way to suppress
      specific gene expression. We designed hammerhead ribozymes directed against
      hepatitis C virus RNA, and investigated their cleavage efficiency and inhibitory
      effect on viral translation in vitro. METHODS: Three hammerhead ribozymes bearing
      different cleavage sites in the core region of hepatitis C virus RNA (genotype
      1b) were designed in this study. Ribozymes and the target hepatitis C virus RNA
      were synthesized by in vitro transcription. The cleavage efficiency was evaluated
      by the ribozyme cleavage assay. The inhibitory effect of the ribozyme on viral
      translation was further studied by the viral translation inhibition assay.
      RESULTS: All ribozymes specifically cleaved the target RNA of 1217 bases at a
      physiological temperature in a dose-dependent manner, with the specific cleavage
      increasing with a longer incubation period. The target RNA was cleaved most
      efficiently by the ribozyme with the cleavage site located nearest to the
      initiation codon. In the viral translation inhibition assay, all ribozymes showed
      a significant inhibitory effect on viral translation. The ribozyme with the
      cleavage site located farthest from the initiation codon blocked viral
      translation most efficiently, and demonstrated almost 70 to 80% inhibition. For
      ribozymes with the T7 transcription terminator sequence, both the target RNA
      cleavage and the inhibition of viral translation tended to be achieved less
      efficiently by ribozymes with T7 terminator than by those without it.
      CONCLUSIONS: These findings suggest that ribozyme-mediated hepatitis C virus RNA
      cleavage may serve as a new strategy in the treatment of hepatitis C virus
      infection.

PMID- 9252076
TI  - Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence do not
      predict the response to recombinant interferon-alfa therapy in French patients.
AB  - BACKGROUND/AIMS: Studies of HCV quasispecies during interferon treatment have
      shown the selection of resistant clones. Enomoto et al. have defined the
      interferon sensitivity-determining region in an amino acid stretch of the HCV-1b
      NS5A region. Patients with a mutant strain before treatment were complete
      responders, whereas those with wild-type HCV-J strain were resistant to
      interferon. The same region was studied in HCV isolates of French patients.
      METHODS: Forty-three HCV-1b chronically infected patients, consisting of 26 non
      responders and 17 complete responders to interferon-alfa treatment (3 MUI tiw for
      6 months), were included retrospectively. We directly sequenced the NS5A(2209
      2248) HCV region of these patients before treatment. The viral load could be
      obtained from six complete responders and 15 non-responders. RESULTS: We detected
      wild-type and intermediate strains, but only two mutant strains were present. One
      of them was found in a non-responder. In three complete responders, we found a
      wild-type strain. The distribution of the various strains was rather different
      from that found in Japan. Before treatment, the viral load was lower in complete
      responders (p=0.01). CONCLUSIONS: Only two mutant strains were detected in our
      study. This could partially explain the low response rate to interferon treatment
      of French HCV-1b-infected patients, although the dose regimen was lower than in
      Japanese studies. Also, wild-type strains were found in some complete responders,
      and no correlation was determined between the mutation number in the NS5A(2209
      2248) region and response to alfa interferon therapy. This may be related to
      epidemiological differences between HCV-1b strains present in France and those in
      Japan. Searching for the mutant NS5A pattern before treatment does not appear to
      be useful in French patients as it is too uncommon.

PMID- 9252078
TI  - Transmission of GBV-C/HGV from drug-addicted mothers to their babies.
AB  - BACKGROUND/AIMS: In 1995, a new flavivirus, GBV-C/HGV was identified. Little
      information is available on the clinical manifestations and epidemiology of GBV
      C/HGV infection. We investigated the risk of mother-to-infant transmission in a
      group of GBV-C/HGV RNA positive women and followed up the GBV-C/HGV infected
      babies. METHODS: Twenty-eight anti-HCV positive women, of whom 25 have been
      intravenous drug users, and their children were included in the study. RNA was
      extracted from serum, reverse transcribed and amplified with primers from the NS5
      region of GBV-C/HGV and 5'-UTR of HCV in a nested polymerase chain reaction.
      Amplified DNA fragments were gel purified and sequenced; the sequences obtained
      were subjected to a phylogenetic analysis. RESULTS: Transmission of GBV-C/HGV
      occurred in 10 (56%) of 18 infants born to GBV-C/HGV positive mothers; all these
      women were drug abusers. Only one (5%) of 19 babies whose mothers were HCV RNA
      positive by polymerase chain reaction, was infected with HCV during the follow
      up. High sequence homology in the NS5 region of GBV-C/HGV isolates in 10 mother
      child pairs suggested mother-to-infant transmission. All 10 babies remained GBV
      C/HGV RNA positive during follow up (2-12 months). None of the GBV-C/HGV infected
      infants became icteric or demonstrated any clinical or biochemical signs of liver
      disease. CONCLUSIONS: Mother-to-infant transmission of GBV-C/HGV may be high, at
      least in HCV-infected, drug-addicted women. In GBV-C/HGV RNA positive infants the
      rate of GBV-C/HGV persistent infection is high, but the infection is not
      accompanied by any symptoms of liver disease.

PMID- 9252079
TI  - Poor association of GBV-C viremia with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The role of the hepatitis GB virus C in chronic liver disease is
      unclear. The clinical findings, results of laboratory tests, pathological
      findings, and outcome after liver resection for hepatocellular carcinoma in
      patients infected or not infected with GB virus C were compared. METHODS: Serum
      samples from 213 patients were tested for hepatitis B virus, hepatitis C virus,
      and GB virus C. Of the 213 patients, 159 had hepatitis C viral RNA or antibodies
      (group 1), seven had both hepatitis C viral RNA or antibodies and hepatitis B
      surface antigen (group 2), 25 had hepatitis B surface antigen (group 3), and 22
      did not have hepatitis C viral RNA, hepatitis C antibodies, or hepatitis B
      surface antigen (group 4). RESULTS: GB virus C RNA was detected in 12 of the 213
      patients. Of the 12 patients, 11 were in group 1 and one was in group 4. There
      were no patients with hepatocellular carcinoma associated with GB virus C RNA
      alone. In groups 1 and 4, there were no differences in clinical findings, results
      of laboratory tests, pathological findings, or outcome after surgery in patients
      with and without GB virus C RNA. CONCLUSIONS: These results indicate a poor
      association of GB virus C viremia with hepatocellular carcinoma. We did not find
      clinically significant interaction between hepatitis C virus and GB virus C.

PMID- 9252080
TI  - Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in
      alcoholic patients.
AB  - BACKGROUND/AIMS: A 4977-base pair deletion has been detected in the hepatic
      mitochondrial DNA of alcoholic patients with microvesicular steatosis, a lesion
      ascribed to impaired mitochondrial beta-oxidation. However, only a single
      deletion had been looked for in this previous study, and it could not be
      determined whether the deletion was preexisting or acquired. Alcohol abuse
      increases the formation of reactive oxygen species in hepatic mitochondria. If
      this effect accelerates the oxidative aging of mitochondrial DNA, several other
      mutations would be expected. METHODS: The mtDNA region extending from nucleotide
      8167 to nucleotide 14246 was screened for the presence of large mitochondrial DNA
      deletions in 58 alcoholic patients and 67 age-matched non-alcoholic controls.
      Hepatic DNA was subjected to polymerase chain reactions that amplified non
      deleted and deleted mitochondrial DNA, respectively, and the boundaries of the
      mitochondrial DNA deletions were sequenced. RESULTS: Only 3% of the non-alcoholic
      controls carried a mitochondrial DNA deletion, whereas 24% of all alcoholic
      patients and 85% of the 13 alcoholic patients with microvesicular steatosis
      exhibited either single or multiple 4977, 5385, 5039 and 5556-base pair
      mitochondrial DNA deletions. No deletion(s) were observed, however, in 13
      patients with microvesicular steatosis due to other causes. CONCLUSIONS: Diverse
      mitochondrial DNA rearrangements are observed in alcoholic patients with
      microvesicular steatosis. We suggest that alcohol abuse leads to premature
      oxidative aging of mitochondrial DNA. Hypothetically, oxidative damage to
      mitochondrial constituents (DNA, proteins and lipids) may favor microvesicular
      fat deposition.

PMID- 9252081
TI  - Therapeutic effects of restricted diet and exercise in obese patients with fatty
      liver.
AB  - BACKGROUND/AIMS: The incidence of obese patients with fatty liver has recently
      increased in Japan as well as in the United States and Europe. Fatty liver may
      occasionally progress to liver cirrhosis. In this study, we have compared the
      effects of restricted diet and exercise versus no treatment in obese patients
      with fatty liver. METHODS: Twenty-five obese patients with fatty liver were
      divided into treated and control groups. Fifteen obese patients followed a
      program of restricted diet (ideal weight x 25 Cal x kg(-1)) and exercise (walking
      or jogging) for a trial period of 3 months. No changes in diet or lifestyle were
      made by the other 10 patients during the same trial period. Blood biochemical
      tests and liver histology were compared in all patients before and after the
      trial. RESULTS: In the treated group, weight, blood biochemical data such as
      aminotransferase, albumin, cholinesterase, total cholesterol and fasting blood
      glucose values, and steatosis were significantly decreased after the trial. In
      the control group, there were no significant differences in the clinical and
      histological findings before and after the trial. CONCLUSIONS: These results
      indicate that restricted diet and exercise therapy, such as walking and jogging,
      are useful means of improving blood biochemical data and histological findings in
      liver tissues related to fatty liver.

PMID- 9252082
TI  - Noninvasive in vivo quantitative assessment of fat content in human liver.
AB  - BACKGROUND/AIMS: Since the introduction of ultrasonography, liver steatosis has
      become an increasingly frequent diagnosis. Both ultrasonography (US) and
      computerized tomography (CT) provide qualitative rather than quantitative
      assessment of fatty infiltration. The objective of this study was to develop a
      noninvasive method for the quantification of the hepatic fat content in vivo. A
      test object containing solutions with CT scan density (CTD) similar to normal
      liver ("liver-equivalent") or "fat-equivalent material" in variable proportions
      was prepared to measure patients with variable degrees of steatosis in vivo.
      RESULTS: A linear correlation (r=0.99, p<0.001) linked CTD and the increasing
      percentage of fat-equivalent material. A CTD calibration curve was derived as a
      reference for the in vivo determinations. In 29 consecutive patients with
      steatosis diagnosed by histology, CTD was linearly correlated (r=0.83, p<0.001)
      with the hepatic fat content (HFC) expressed as percent of the whole liver,
      obtained by a computerized histomorphometric analysis. Based on the calibration
      curve obtained in 29 subjects who underwent liver biopsy, 38 additional
      consecutive steatotic patients were examined and the degree of hepatic fat
      content was calculated. The HFC was linearly correlated (r=-0.86, p<0.001) with
      the liver-to-spleen ratio. CONCLUSIONS: We conclude that the use of test objects
      allows an accurate and reproducible noninvasive quantitative assessment of
      hepatic fat infiltration in humans. This technique may prove useful in the
      evaluation of the natural course and treatment of hepatic steatosis as well as in
      the assessment of donor livers prior to transplantation.

PMID- 9252083
TI  - Cerebral autoregulation in patients with cirrhosis and ascites. A transcranial
      Doppler study.
AB  - BACKGROUND/AIMS: Patients with cirrhosis and ascites usually show alterations of
      systemic hemodynamics and are thus prone to develop arterial hypotension, which
      might result in cerebral hypoperfusion if cerebral autoregulation is impaired.
      METHODS: We evaluated cerebral autoregulation in 15 patients with cirrhosis and
      ascites and 15 healthy subjects by monitoring mean blood flow velocity in the
      middle cerebral artery and arterial pressure during supine rest and passive
      tilting. RESULTS: Tilt provoked a drop of arterial pressure in both groups.
      Control subjects had a prompt recovery of mean flow velocity and a progressive
      recovery of arterial pressure, so that, after 120 s, both parameters had returned
      to baseline: at 20 s the recovery of flow velocity was faster (p<0.01) than that
      of blood pressure. By contrast, patients with cirrhosis had a delayed and
      incomplete recovery of both parameters (p<0.01 vs healthy subjects). In eight
      patients, the recovery of mean flow velocity paralleled that of arterial
      pressure, indicating an impaired cerebral autoregulation. These patients had a
      worse liver function, a higher cardiac index and lower peripheral resistance.
      CONCLUSIONS: Cerebral autoregulation is often impaired in patients with cirrhosis
      and ascites. These patients can develop cerebral hypoperfusion if arterial
      pressure falls abruptly.

PMID- 9252084
TI  - MRI findings in chronic hepatic encephalopathy depend on portosystemic shunt:
      results of a controlled prospective clinical investigation.
AB  - BACKGROUND/AIMS: Deterioration of hepatic encephalopathy is a major concern with
      the transjugular intrahepatic portosystemic shunt procedure. Symmetric
      hyperintense globus pallidus on T1-weighted cranial magnetic resonance imaging in
      patients with liver cirrhosis anticipates hepatocerebral disease. It is
      hypothesized that hepatic encephalopathy and basal ganglia signal intensity
      progress in patients with cirrhosis of the liver undergoing transjugular
      intrahepatic portosystemic shunt. METHODS: Twenty-four patients were randomized
      to undergo either transjugular intrahepatic portosystemic shunt or elective
      sclerotherapy. At study entry and 6 months after randomization, neurologic
      assessment, psychometric tests, standard EEG, and magnetic resonance imaging were
      performed. The severity of liver failure was graded using Child-Pugh's
      classification. The signal intensity of the globus pallidus was determined on
      sagittal T1-weighted magnetic resonance imaging. RESULTS: The T1-weighted signal
      intensity of the globus pallidus on magnetic resonance imaging significantly
      increased after transjugular intrahepatic portosystemic shunt placement (p<0.01),
      but not with elective sclerotherapy. At follow-up, neurological symptoms
      indicating decline of mental status and motor performance were somewhat more
      prevalent in transjugular intrahepatic portosystemic shunt patients. Significant
      deterioration of EEG abnormalities occurred in patients treated with transjugular
      intrahepatic portosystemic shunt as opposed to elective sclerotherapy (p<0.01).
      CONCLUSIONS: Transjugular intrahepatic portosystemic shunt procedure increases
      hyperresonant globus pallidus on magnetic resonance imaging. Neuropsychiatric
      evaluation shows advancing hepatic encephalopathy, in particular with
      transjugular intrahepatic portosystemic shunt; however, it does not parallel the
      augmentation of pallidal signal intensity on magnetic resonance imaging.

PMID- 9252085
TI  - Is inadequate thrombopoietin production a major cause of thrombocytopenia in
      cirrhosis of the liver?
AB  - BACKGROUND/AIMS: Thrombocytopenia secondary to cirrhosis of the liver and portal
      hypertension is a well-known complication of advanced stage liver disease, but
      theories about the underlying pathogenetic mechanisms, mostly centering on
      splenic sequestration and destruction of platelets, have failed to solve the
      problem so far. METHODS: Peripheral platelet count and thrombopoietin levels in
      human plasma were measured in 28 patients with cirrhosis of the liver. Seven of
      those patients underwent orthotopic liver transplantation and five patients
      portal decompression by transjugular intrahepatic portosystemic shunt.
      Thrombopoietin plasma levels were followed for 14 days after the interventions.
      RESULTS: No measurable thrombopoietin was detectable in the plasma of 28
      thrombocytopenic patients with cirrhosis of the liver, in contrast to
      thrombocytopenic patients without liver disease. Seven of these patients with
      cirrhosis underwent orthotopic liver transplantation, resulting in a rise of
      thrombopoietin levels within 2 days after transplantation. The rise in platelet
      number followed with a mean lag of 6 days, and shortly thereafter, thrombopoietin
      levels returned to levels below the limit of detection. Five patients with
      thrombocytopenia, who underwent only decompression of portal hypertension, showed
      no rise in either thrombopoietin levels or platelet count. CONCLUSIONS:
      Thrombocytopenia associated with liver disease may at least in part be
      attributable to inadequate thrombopoietin production in the failing liver.

PMID- 9252086
TI  - Protein C, protein S and antithrombin III in children with portal vein
      obstruction.
AB  - BACKGROUND/AIMS: Portal vein obstruction is the most common single cause of
      portal hypertension in children and its cause is unknown in most instances. The
      aim of the present study was to evaluate the incidence of protein C, protein S
      and antithrombin III deficiencies and to screen for possible genetic deficiencies
      of these proteins. METHODS: A prospective study was undertaken in 20 consecutive
      children with portal vein obstruction, their parents and 20 matched healthy
      children. RESULTS: Children with portal vein obstruction displayed a reduction in
      protein C (p<0.05), protein S (p<0.0001), and antithrombin III (p<0.001)
      activities as compared with controls. Protein C and protein S activities were
      below 60% in nine and eleven of the children with portal vein obstruction,
      respectively, and antithrombin III activities were below or equal to 85% in ten
      of them. Repeated assay of protein C activity in seven children following a
      surgical portosystemic shunt showed a decrease as compared with preoperative
      values. Protein C, protein S and antithrombin III were normal in all parents,
      except two mothers in whom the levels of protein S activity and protein S antigen
      were found to be either below or at the lower limit of the normal range.
      CONCLUSIONS: These results indicate that protein C, protein S and/or antithrombin
      III deficiencies are frequently found in children with portal vein obstruction
      but are not likely to be of genetic origin in most cases.

PMID- 9252087
TI  - Expression and therapeutic response related to apolipoprotein E polymorphism in
      primary biliary cirrhosis.
AB  - BACKGROUND/AIMS/METHODS: Apolipoprotein E polymorphism, affecting intestinal
      absorption and biliary secretion of bile acids, might also contribute to the
      variable course and response to drug treatment of primary biliary cirrhosis. To
      test this possibility, we studied the apo E gene frequency, and the expression
      and response to drug therapy in different apo E isoforms of 88 patients with
      primary biliary cirrhosis, randomized to ursodeoxycholic acid, colchicine or
      placebo treatments for 2 years. RESULTS: The frequency of the epsilon2 allele was
      2.4 times higher (p<0.01) in the patients with primary biliary cirrhosis compared
      with the Finnish population. At entry the patients with the epsilon4 allele were
      significantly younger (p<0.01) than those with other epsilon alleles, while the
      severity of primary biliary cirrhosis was similar in the three apolipoprotein E
      phenotypes. Liver enzymes, acute hepatic inflammation, serum total and low
      density lipoprotein cholesterol were decreased by ursodeoxycholic acid only in
      the patients with the epsilon4 and homozygous epsilon3 alleles, but not in those
      with the epsilon2 allele. Improvements of liver enzyme tests by ursodeoxycholic
      acid were more marked in the patients with the epsilon4 than other epsilon
      alleles. CONCLUSIONS: The present data show that in primary biliary cirrhosis the
      epsilon2 allele is overrepresented, and suggest that the expression of primary
      biliary cirrhosis and response of the disease to ursodeoxycholic acid treatment
      are closely related to the apo E polymorphism.

PMID- 9252088
TI  - The combination of ursodeoxycholic acid and methotrexate for primary biliary
      cirrhosis is not better than ursodeoxycholic acid alone.
AB  - BACKGROUND/AIMS: Many therapies have been tried in primary biliary cirrhosis. It
      has been suggested that a combination of ursodeoxycholic acid and methotrexate
      may offer advantages. Because the benefit and safety of this combination is
      uncertain, we conducted this prospective, randomized, double-blind, controlled
      trial. METHODS: Twenty-five patients with well-defined primary biliary cirrhosis
      were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus
      methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48
      weeks. Clinical, biochemical and histologic evolution were assessed. RESULTS: In
      both groups the clinical response was similar and heterogeneous. In patients of
      ursodeoxycholic acid alone group, biochemical and histologic changes were
      comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48
      weeks. The addition of methotrexate was not associated with substantial adverse
      affects. CONCLUSIONS: The use of methotrexate in combination with ursodeoxycholic
      acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor
      was substantial toxicity added. Unless larger and longer controlled trials with
      clinical, biochemical and histologic controls show it to be a safe and effective
      therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should
      not be used as a proven and accepted treatment.

PMID- 9252089
TI  - Circulating markers for biosynthesis of cholesterol and bile acids are not
      depressed in asymptomatic gallstone subjects.
AB  - BACKGROUND/AIMS: Cholesterol gallstone disease is often associated with an
      increased biliary secretion rate of cholesterol, which may be due to
      abnormalities in hepatic cholesterol metabolism. The aim of the present study was
      to investigate whether gallstone subjects may have an underlying defect in
      hepatic cholesterol and bile acid formation. METHODS: In 41 asymptomatic
      gallstone subjects, randomly selected from a population of both sexes 40 and 60
      years of age, and in 72 age- and sex-matched controls, plasma levels of
      lathosterol (reflecting hepatic HMG CoA reductase activity) and 7alpha-hydroxy-4
      cholesten-3-one (reflecting cholesterol 7alpha-hydroxylase activity) were
      analysed. In a subgroup of gallstone subjects and controls, plasma levels of 27
      hydroxy cholesterol were also determined. RESULTS: The gallstone subjects had
      normal plasma levels of cholesterol but displayed 20-25% higher plasma levels of
      triglycerides compared with the controls. The plasma level of lathosterol was not
      significantly different between the two groups of subjects whereas the plasma
      level of 7alpha-hydroxy-4-cholesten-3-one was about 40% higher in the gallstone
      subjects compared with the controls. Positive correlations were obtained between
      plasma levels of 7alpha-hydroxy-4-cholesten-3-one and triglycerides in both
      groups of subjects. The plasma level of 27-hydroxy cholesterol was similar in
      gallstone subjects and controls. CONCLUSIONS: The previously reported
      hypersecretion of cholesterol in gallstone patients is not due to a single
      metabolic defect leading to increased hepatic synthesis of cholesterol or
      decreased catabolism of cholesterol to bile acids via 7alpha-hydroxylation or 27
      hydroxylation of cholesterol.

PMID- 9252090
TI  - Expression of liver functions following sub-lethal and non-lethal doses of allyl
      alcohol and acetaminophen in the rat.
AB  - BACKGROUND/AIMS: To relate severity of intoxication with allyl alcohol and
      acetaminophen to modulated hepatic gene expression of liver functions and
      regeneration. METHODS: Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g
      per kg body weight, or allyl alcohol 100 or 125 microl by gastric tube, doses
      producing no and about 30% mortality, respectively, within 2 days. In the morning
      2, 6, 12, 24, and 36 h after intoxication, RNA was extracted from liver tissue.
      By slot blot hybridization mRNA levels were determined for acute phase proteins,
      enzymes involved in ammonia elimination and urea synthesis, and for proteins
      related to liver regeneration. RESULTS: After allyl alcohol, mRNA of "positive"
      acute phase proteins was higher than after acetaminophen and increased with the
      dose, whereas after acetaminophen it decreased with the dose. The mRNA of the
      urea cycle enzymes and glutamine synthetase was uniformly reduced by allyl
      alcohol, whereas that of most urea cycle enzymes was above the controls after the
      non-lethal, but not after the sub-lethal, dose of acetaminophen. The mRNA of
      glutamine synthetase was significantly more reduced by acetaminophen than by
      allyl alcohol. The mRNA of cell-cycle dependent proteins was greatly reduced
      after both toxins, more after the higher dose. CONCLUSIONS: The study shows that
      acetaminophen intoxication inhibits or fails to induce the expression of acute
      phase proteins in contrast to allyl alcohol intoxication. Allyl alcohol
      suppressed the expression of urea cycle enzymes, whereas that of the rate
      limiting enzymes carbamoylphosphate synthase and argininosuccinate synthetase was
      increased by the non-lethal but not by the sub-lethal dose of acetaminophen. The
      expression of the cell-cycle dependent proteins was more suppressed after the sub
      lethal than after the non-lethal dose of both toxins. The data support the view
      that a fatal outcome of the intoxications depends more on the ability to
      regenerate than on the maintenance of liver-specific functions.

PMID- 9252091
TI  - Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is
      followed by impairment of hepatic microvascular blood flow.
AB  - BACKGROUND: Recent studies provide evidence that nitric oxide (NO) has beneficial
      effects in hepatic ischemia/reperfusion injury. The purpose of this study was to
      evaluate whether nitric oxide is involved in the regulation of hepatic
      microvascular perfusion after warm hepatic ischemia. Therefore, we performed a
      study using in vivo fluorescence microscopy. METHODS: Clamping of the left liver
      lobe was performed in male Wistar rats for the duration of 70 min. One
      experimental group (n=8) received L-NAME (Nw-nitro-L-arginine methyl ester
      hydrochloride), an NO-synthase inhibitor, 1 min prior to reperfusion. A second
      experimental group (n=8) received L-arginine (NO-substrate) continuously infused
      throughout the observation period. Controls (n=8) received equivalent volumes of
      an isotonic solution and underwent the same procedures. Hepatic microvascular
      blood flow and leukocyte-endothelial cell interaction was studied between 20 and
      90 min after reperfusion using in vivo fluorescence microscopy. RESULTS:
      Inhibition of NO-synthesis during reperfusion by application of L-NAME caused a
      marked decrease in sinusoidal blood flow velocity. Furthermore, we noted an
      increase of non-perfused sinusoids in this group. Treatment with L-arginine
      improved functional perfusion of hepatic acini and reduced significantly the
      number of adherent leukocytes in sinusoids and venules compared to control
      animals. CONCLUSIONS: Our results provide further evidence that NO maintains
      postischemic hepatic microvascular perfusion and that inhibition of NO synthesis
      has detrimental effects on hepatic microhemodynamics during reperfusion.

PMID- 9252092
TI  - Suppression of human hepatoma in mice through adoptive transfer of immunity to
      the hepatitis B surface antigen.
AB  - BACKGROUND/AIMS: Adoptive transfer of immunity against hepatitis B surface
      antigen (HBsAg) has previously been shown to occur in mice and humans through
      transplantation of bone marrow cells from donors immunized against HBsAg (anti
      HBs) to non-immune recipients. In the present study we evaluated the effect of
      adoptive transfer of immunity to HBsAg on the growth of HbsAg-secreting
      hepatocellular carcinoma (HCC) xenografts in athymic mice. METHODS:
      Immunocompetent mice were immunized with recombinant HBsAg. Bone marrow cells
      from anti-HBs+ mice were injected intravenously to irradiated athymic Balb/c mice
      which had been previously transplanted subcutaneously with Hep3B human hepatoma
      cells. Treatment groups included mice receiving bone marrow transplantation from
      HBV-immunized (anti-HBs positive) and non-immunized (anti-HBs negative) donors.
      RESULTS: At 9 weeks post bone marrow transplantation, tumor volume and serum
      alpha-fetoprotein levels in athymic mice receiving HBV-immune bone marrow cells
      were 11.5 mm3 and 363 ng/ml, respectively, as compared to 1579 mm3 and 19,000
      ng/ml, in recipients of non-immune bone marrow transplantation (p<0.005). T-cell
      depletion of antiHBs+ immune bone marrow prior to transplantation decreased the
      anti-tumor effect but did not abolish it. A mild nonspecific, bone marrow
      derived, graft versus tumor effect was observed in mice transplanted with human
      hepatoma cells that do not express HBsAg. CONCLUSIONS: Adoptive transfer of
      immunity to HBV facilitates suppression of experimental human HCC expressing
      HBsAg. This effect is the result of a combination of specific anti-viral surface
      antigen effect and a nonspecific graft versus tumor effect.

PMID- 9252093
TI  - Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary
      excretion of plasma non-transferrin-bound iron in rats.
AB  - BACKGROUND/AIMS: It is well documented that levels of plasma non-transferrin
      bound iron (NTBI), a particularly toxic form of iron, are increased in iron
      overload disorders. In light of the pathogenetic importance of NTBI in chronic
      iron overload, we have studied the ability of new orally active iron chelators to
      promote the biliary excretion of iron originating as plasma 55Fe-NTBI. METHODS:
      Biliary iron kinetics of plasma 55Fe-labeled NTBI and cumulative recoveries of
      55Fe in bile were determined in normal and carbonyl iron-loaded rats receiving a
      single intragastric dose of iron chelator. These chelators were the novel
      hydroxypyridin-4-one compounds CP102, CP41, and their respective pro-drugs CP117
      and CP165. RESULTS: The cumulative recovery of 55Fe in bile of normal rats was
      increased by 5.2-, 7.9-, 11.5-, and 9.2-fold with CP102, CP117, CP41 and CP165,
      respectively. In iron overloaded rats, these compounds increased the cumulative
      recovery by 28.6-, 48.6-, 72.6-, and 32-fold, respectively. All the chelators had
      a choleretic effect, were metabolized by the liver as demonstrated by HPLC study
      of bile, and were not cytotoxic since normal plasma transaminase levels were
      maintained at the end of the experiments. CONCLUSIONS: These chelators have
      potential interest for the treatment of iron overload conditions and may offer
      advantages over simple N-alkyl-hydroxypyridinones such as deferiprone (CP20, L1).

PMID- 9252094
TI  - Prolyl 4-hydroxylase inhibitor (HOE 077) inhibits pig serum-induced rat liver
      fibrosis by preventing stellate cell activation.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effect and
      mechanism of fibrosuppression by a newly synthesized prolyl 4-hydroxylase
      inhibitor [HOE 077, 2, 4-pyridine dicarboxylic acid bis [(2-methoxyethyl) amide]]
      on pig serum-induced liver fibrosis in the rat. METHODS: Male Wistar rats
      received 0.5 ml of pig serum twice a week for 10 weeks with 0, 100 or 200 ppm of
      HOE 077. At the end of the experiment, the hydroxyproline content of the liver,
      and alanine aminotransferase were measured. Histological stains used were HE,
      azan and a stain for alpha-smooth muscle actin (alpha-SMA). Electron microscopy
      was also performed. Messenger RNA expressions of type I and III procollagen were
      examined by Northern blot analysis. alpha-SMA positive cells and fibers with azan
      staining were assessed as percent area of the tissue specimen, using an image
      analysis system. RESULTS: Rats that received pig serum for 10 weeks showed an
      increased liver hydroxyproline content of 318+/-39 microg/g wet weight (n=15).
      HOE 077 at doses up to 200 ppm significantly (p<0.01) reduced this increase of
      liver hydroxyproline content (181+/-39 microg/g wet weight, n=15) in accordance
      with improved histological findings. 200 ppm of HOE 077 significantly reduced
      mRNA expressions of alpha2(I) (486+/-102 vs 151+/-36, p<0.01) and alpha1(III)
      (276+/-127 vs 160+/-67, p<0.05) procollagen and percent area of alpha-SMA
      positive cells (2.94+/-2.14 vs 1.17+/-0.88%). Electron microscopy revealed that
      200 ppm of HOE 077 prevented the loss of fat droplets. CONCLUSIONS: A prolyl 4
      hydroxylase inhibitor (HOE 077) prevented pig serum-induced rat liver fibrosis by
      inhibiting stellate cell activation.

PMID- 9252095
TI  - Effects of eicosanoids on lipopolysaccharide-induced ornithine decarboxylase
      activity and polyamine metabolism in the mouse liver.
AB  - BACKGROUND/AIMS: During endotoxic shock, arachidonic acid is released from the
      inflammatory cell membranes and is metabolized to form eicosanoids, which modify
      the deleterious effects of lipopolysaccharide (LPS) on liver function. However,
      it is not known which prostaglandins (PGs) or leukotrienes (LTs) are produced or
      how they affect the LPS-treated liver. As LPS treatment elevates hepatic
      ornithine decarboxylase (ODC) activity and affects the polyamine levels of the
      mouse liver, this study was carried out to examine the effects of eicosanoids and
      their inhibitors on the induction of ODC activity and polyamine levels in the LPS
      treated mouse liver. METHODS: LPS in the presence or absence of other drugs was
      intraperitoneally administered to 6-week-old mice and the livers were then
      removed. The hepatic ODC activity, polyamine levels, and level of ODC mRNA were
      determined. RESULTS: The levels of LPS-induced ODC activity, the putrescine (PUT)
      and N1-acetylspermidine (A-SPD) were reduced by the administration of PGE1. ODC
      activity was enhanced by the administration of corticosterone, AA-2414 (an
      antagonist of thromboxane (TX) A2) and TXB2, whereas the A-SPD level was reduced
      by corticosterone and AA-2414 treatment. The level of ODC mRNA changed in
      parallel with the change in ODC activity. CONCLUSIONS: PGE1 may reduce the LPS
      induced production of inflammation-accelerating cytokines and reduce the level of
      ODC activation. Corticosterone and AA-2414 treatment may attenuate the LPS
      induced production of eicosanoids, and enhance the LPS-induced ODC activation. It
      is possible that the eicosanoids produced by LPS treatment inhibit ODC activation
      during endotoxic shock.

PMID- 9252096
TI  - Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and
      decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis
      (EUROHEP).
AB  - BACKGROUND/AIMS: The role of interferon alfa treatment in improving morbidity
      endpoints in patients with chronic hepatitis C infection is currently under
      debate. The aim of this study was to evaluate the effectiveness of interferon in
      preventing hepatocellular carcinoma and decompensation in cirrhosis type C.
      METHODS: A retrospective cohort study was carried out on 329 consecutive
      Caucasian patients with cirrhosis followed for a mean period of 5 years at seven
      tertiary care university hospitals. Inclusion criteria were biopsy-proven
      cirrhosis, anti-HCV positivity, abnormal serum aminotransferase levels and
      absence of complications of cirrhosis. RESULTS: The yearly incidence of
      hepatocellular carcinoma was 2.3% for 136 untreated patients and 1.0% for 193
      patients treated with interferon alfa. The yearly incidence of hepatic
      decompensation was 5.7 for untreated and 1.5 for the treated patients. Fourteen
      (7%) of 193 treated patients showed sustained aminotransferase normalization and
      none of them developed complications of cirrhosis. At enrollment, untreated
      patients were older and had more severe liver disease than patients treated with
      interferon. After adjustment for clinical and serologic differences at entry
      between treated and untreated patients, the 5-year estimated probability of the
      occurrence of hepatocellular carcinoma was 2.1% and 2.7% and of decompensation
      was 7% and 11% for treated and untreated cases, respectively. CONCLUSIONS: This
      analysis did not detect any significant benefit of interferon alfa on morbidity
      in patients with compensated cirrhosis type C, although it suggests a reduction
      in complications of cirrhosis for those with a sustained response to therapy, and
      it indicates the need for better therapies.

PMID- 9252097
TI  - Protein-losing enteropathy secondary to hepatic venous outflow obstruction after
      liver transplantation.
AB  - A 42-year-old man with a history of repeated abdominal surgery and lymph node
      tuberculosis underwent orthotopic liver transplantation for primary sclerosing
      cholangitis. Two years after transplantation, this patient developed a severe
      protein-losing enteropathy with no evidence of cardiac disease or
      lymphoproliferative disorder. Imaging work-up revealed hemodynamically
      significant stenosis of the supra-hepatic caval anastomosis, which was treated by
      percutaneous balloon angioplasty. All clinical and biochemical disorders resolved
      within 1 month after percutaneous dilatation, but relapsed simultaneously with
      recurrent anastomotic stenosis 15 months later. Repeat caval angioplasty resulted
      in rapid recovery, which strongly suggests that hepatic venous outflow
      obstruction was responsible for the protein-losing enteropathy in this patient.

PMID- 9252098
TI  - Spontaneous regression of hepatocellular carcinoma.
AB  - A 72-year-old Caucasian woman suffered from histologically-proven advanced
      hepatic cancer, for which she received no treatment. She had been a regular
      drinker for a long time. Serologic markers for hepatitis B and C were negative.
      In spite of her poor prognosis, she remained in good clinical condition and at 14
      months of follow up the hepatocellular carcinoma could not be visualised any more
      radiologically. At that time the serum alpha foetoprotein concentration was
      normal. At present, 28 months after diagnosis, the patient is doing well and her
      tumour still appears to be in complete spontaneous remission.

PMID- 9252099
TI  - Images in hepatology. Large splenorenal shunt in portal venous obstruction.

PMID- 9252100
TI  - Pathophysiological changes in cerebral circulation, oxidative metabolism and
      blood-brain barrier in patients with acute liver failure. Tailored cerebral
      oxygen utilization.

PMID- 9252101
TI  - Energy and protein requirements of patients with chronic liver disease.

PMID- 9252102
TI  - Immunogenetic factors and disease severity in chronic hepatitis C.

PMID- 9252103
TI  - Near infrared absorption spectra of human deoxy- and oxyhaemoglobin in the
      temperature range 20-40 degrees C.
AB  - Temperature-dependent spectral changes of human haemoglobin A (HbA) derivatives
      were investigated in the range 20-40 degrees C. The intensity of the deoxy-HbA
      decreased by 3-3.5%, while that of oxy- and met-HbA by less than 1%, when the
      temperature increased from 20 degrees to 40 degrees C. The present findings can
      be employed to improve the algorithms used in in vivo near infrared spectroscopy.

PMID- 9252104
TI  - Nucleotide sequence of a gene cluster encoding NusG and the L11-L1-L10-L12
      ribosomal proteins from the thermophilic archaeon Sulfolobus solfataricus.
AB  - The complete nucleotide sequence of a gene cluster encoding the NusG and the L 11
      L1-L10-L12 ribosomal proteins from the thermophilic crenarchaeon Sulfolobus
      solfataricus has been determined. The genes are arranged in the same order as the
      equivalent genes in the rif region of Escherichia coli. The ribosomal proteins
      exhibit between 66% (L10) and 80% (L12) identity with their respective
      equivalents from Sulfolobus acidocaldarius. The short distance (5 nucleotides)
      between the nusG stop codon and the L11 start codon suggests that nusG and the
      genes for the ribosomal proteins are transcribed as a single unit.

PMID- 9252105
TI  - X-ray crystal structure determination and molecular dynamics simulation of
      prophospholipase A2 inhibited by amide-type substrate analogues.
AB  - X-ray crystal structures of bovine pancreas prophospholipase A2 (proPLA2)
      inhibited by two amide-type inhibitors, [(R)-2-dodecanoyl-amino-1
      hexanolphosphocholine (DAHPc) and (R)-2-dodecanoylamino-1-hexanolphosphoglycol
      (DAHPg)], were determined to R = 0.208 and 0.215 using reflections with up to 2.1
      A resolution, respectively. Both complex crystals lacked defined electron
      densities for the prosequence of the N-terminal and for a loop region consisting
      of residues 65-70, retaining the disordered feature observed in free proPLA2
      despite stabilization due to complex formation. The polar and nonpolar moieties
      of the amide-type inhibitors were located in the calcium-binding pocket and in
      the N-terminal alpha-helical hydrophobic region of the enzyme, respectively. As
      for the amide group of the inhibitor, which is lacking in the true substrate, a
      strong hydrogen bond was formed between the NH of the inhibitor and the
      unprotonated N(delta1) atom of His-48, resulting in the tight binding of the
      inhibitor to proPLA2, as well as to PLA2. The 20-30 times more potent inhibitory
      activity of DAHPg than DAHPc toward PLA2 could be explained by hydrogen bond
      formation between the glycol OH of DAHPg and the carbonyl O of Asp-49. The seven
      residues of the N-terminal prosequence of proPLA2, though disordered, block the
      access of a water molecule to Ala-1 of PLA2 or change the hydrogen-bonding
      property of Ala-1 alpha-amino group, resulting in breakage of the water-mediated
      hydrogen-bond network which is commonly formed in PLA2. The results of molecular
      dynamics (MD) calculation in an aqueous solution at 300 K indicate that this,
      rather than the close contact between the prosequence and the residues 65-70 loop
      region, is the main reason why the latter region becomes flexible in proPLA2,
      compared with in PLA2.

PMID- 9252106
TI  - Probing Flp: a new approach to analyze the structure of a DNA recognizing protein
      by combining the genetic algorithm, mutagenesis and non-canonical DNA target
      sites.
AB  - A topological and functional overview of a DNA recognition protein with unknown
      structure can be achieved by combining three different, but complementary
      approaches: modeling by the genetic algorithm, functional analysis of mutated
      variants, and testing the target DNA using non-canonical oligonucleotides. As an
      example we choose the Flp protein, a site-specific recombinase from Saccharomyces
      cerevisiae. We derive the topological outline including the DNA binding cleft,
      examine DNA binding regions by deletional and mutational analysis, and analyze
      the DNA binding site using 7-deazaadenine, 7-deazaguanine, inosine and 4-O
      methylthymine as probes. The combined data offer a comprehensive sketch of a
      plausible protein architecture for Flp. The structure is detailed enough to
      verify the prediction accuracy for different peptide regions from pre-existing
      data and by new experimental design.

PMID- 9252107
TI  - Association of the anti-hen egg lysozyme antibody HyHEL-5 with avian species
      variant and mutant lysozymes.
AB  - The energetics of association of the murine anti-hen egg lysozyme antibody HyHEL
      5 with bobwhite quail lysozyme, California quail lysozyme, and the Arg45-->Lys
      mutant of hen egg lysozyme was characterized by isothermal titration calorimetry.
      The association of each lysozyme with HyHEL-5 is enthalpically driven in the
      temperature range 10 degrees C to 37 degrees C. The calorimetric results indicate
      that the salt-links between Arg45 and Arg68 of hen egg lysozyme and GluH50 on the
      HyHEL-5 paratope are energetically important in HyHEL-5/HEL association. In
      contrast to previous studies, the results suggest that the three characteristic
      'quail' mutations affect the energetics of antibody/antigen association, even
      though they are buried and not in direct contact with the antibody.

PMID- 9252108
TI  - A prediction of DPP IV/CD26 domain structure from a physico-chemical
      investigation of dipeptidyl peptidase IV (CD26) from human seminal plasma.
AB  - Human DPP IV, isolated from seminal plasma by means of immobilised adenosine
      deaminase, occurs in different forms which are distinguishable by net charge and
      native molecular weight. Charge differences arise primarily from different
      degrees of glycosylation containing various amounts of sialic acid. The majority
      of DPP IV isolated from total seminal plasma consists of the extracellular part
      of the protein starting at Gly-31. It is a very stable protein resisting high
      concentrations of denaturant. Unfolding experiments under reducing conditions are
      indicative of the existence of at least two domains which function independently.
      One of these domains is highly stabilised by disulfide bonds. Disruption of the
      disulfide bonds does not affect the activity, the dimeric state nor the adenosine
      deaminase binding properties of the protein but renders it more susceptible to
      proteolysis. The low-angle X-ray scattering spectrum is consistent with a model
      for a protein containing two subunits, each composed of three domains linked by
      flexible regions with low average mass. The secondary structure composition,
      determined by FTIR spectrometry, indicates that 45% of the protein consists of
      beta-sheets, which is higher than expected from computed secondary structure
      predictions. Our results provide compelling experimental evidence for the three
      domain structure of the extracellular part of DPP IV.

PMID- 9252109
TI  - Purification and characterization of isocitrate dehydrogenase from a
      hyperthermophilic archaebacterium, Caldococcus noboribetus.
AB  - Isocitrate dehydrogenase from a hyperthermophilic archaebacterium Caldococcus
      noboribetus produced in Escherichia coli was purified. The purification was
      performed by heat treatment at 80 degrees C followed by single column
      chromatography. N-terminal amino acid sequencing analysis revealed that the N
      terminal methionine is removed from the purified enzyme. Gel filtration analysis
      suggests that the enzyme has a homodimeric structure with a molecular weight of
      90,000. The isoelectric point of the enzyme was estimated to be 5.6 by
      isoelectric focusing electrophoresis. The circular dichroism spectrum suggests
      that the enzyme has a secondary structure consisting of 23% alpha-helix and 34%
      beta-sheet. Enzymatic activity was observed under neutral pH, and the highest
      specific activity was obtained using cacodylic acid-KOH (pH 7.0) buffer. MgCl2 or
      MnCl2 was essential for the activity, and KCl concentrations higher than 0.33 M
      had an inhibitory effect on it. Apparent Km values were 72 and 43 microM for D,L
      isocitrate and NADP, respectively. The enzyme showed extremely high stability
      against heat treatment, and no activity loss was observed by the treatment at 80
      degrees C. The specific activity of the enzyme increased as temperature rose.
      Nearly no activity was observed at 40 degrees C or lower.

PMID- 9252110
TI  - Conformation of thermally denatured RNase T1 with intact disulfide bonds: a study
      by small-angle X-ray scattering.
AB  - Small-angle X-ray scattering of RNase T1 with intact disulfide bonds was measured
      at 20 degrees and 60 degrees C in order to get insight into the structural
      changes of the protein caused by thermal denaturation. The radius of gyration
      increases from R(G)= 1.43 nm to R(G) = 2.21 nm. The conformations of the
      molecules at 60 degrees C are similar to those of ring-shaped random walk chains.
      However, the molecules are more compact than one would expect under theta
      conditions due to attractive interactions between the chain segments. The volume
      needed for free rotation of the thermally unfolded protein molecules about any
      axis in solution is five times greater than in the native state whereas the
      hydrodynamic effective volume is increasing only two times.

PMID- 9252112
TI  - Computer analysis of phytochrome sequences and reevaluation of the phytochrome
      secondary structure by Fourier transform infrared spectroscopy.
AB  - A repertoire of various methods of computer sequence analysis was applied to
      phytochromes in order to gain new insights into their structure and function. A
      statistical analysis of 23 complete phytochrome sequences revealed regions of non
      random amino acid composition, which are supposed to be of particular structural
      or functional importance. All phytochromes other than phyD and phyE from
      Arabidopsis have at least one such region at the N-terminus between residues 2
      and 35. A sequence similarity search of current databases indicated striking
      homologies between all phytochromes and a hypothetical 84.2-kDa protein from the
      cyanobacterium Synechocystis. Furthermore, scanning the phytochrome sequences for
      the occurrence of patterns defined in the PROSITE database detected the signature
      of the WD repeats of the beta-transducin family within the functionally important
      623-779 region (sequence numbering of phyA from Avena) in a number of
      phytochromes. A multiple sequence alignment performed with 23 complete
      phytochrome sequences is made available via the IMB Jena World-Wide Web server
      (http://www.imb-jena.de/PHYTO.html). It can be used as a working tool for future
      theoretical and experimental studies. Based on the multiple alignment striking
      sequence differences between phytochromes A and B were detected directly at the N
      terminal end, where all phytochromes B have an additional stretch of 15-42 amino
      acids. There is also a variety of positions with totally conserved but different
      amino acids in phytochromes A and B. Most of these changes are found in the
      sequence segment 150-200. It is, therefore, suggested that this region might be
      of importance in determining the photosensory specificity of the two
      phytochromes. The secondary structure prediction based on the multiple alignment
      resulted in a small but significant beta-sheet content. This finding is confirmed
      by a reevaluation of the secondary structure using FTIR spectroscopy.

PMID- 9252111
TI  - Combined pressure/heat-induced inactivation of butyrylcholinesterase.
AB  - The combined effects of pressure and temperature on the activity of
      butyrylcholinesterase (BuChE) were investigated in the pressure range from 10(-3)
      to 5 kbar and temperature range from -10 degrees C to 70 degrees C. Inactivation
      of the enzyme showed a complex dependence on pressure and temperature. Under
      moderate pressures (1-3 kbar) at temperatures 40-65 degrees C BuChE was resistant
      to heat inactivation; under other conditions of pressure and temperature, the
      action of both parameters was synergistic and caused inactivation. Results
      allowed to construct a pressure-temperature kinetic phase diagram for the enzyme
      inactivation. The elliptic diagram for the irreversible transition active-
      >inactive BuChE as a function of both pressure and temperature has a positive
      angular coefficient. This indicates that pressure acts as a stabilizer of BuChE
      against heat denaturation.

PMID- 9252113
TI  - Azotobacter vinelandii glucose 6-phosphate dehydrogenase properties of NAD- and
      NADP-linked reactions.
AB  - Glucose 6-phosphate oxidation, catalyzed by purified Azotobacter vinelandii
      glucose 6-phosphate dehydrogenase, was studied with respect to the selective
      utilization of NAD, NADP, thionicotinamide adenine dinucleotide or
      thionicotinamide adenine dinucleotide phosphate as coenzyme. A sigmoidal
      relationship was observed for the effect of substrate concentration on initial
      velocities when either NAD, NADP or thionicotinamide adenine dinucleotide was
      used as coenzyme, with N values from the Hill equation equalling 2.0, 1.7, and
      1.7, respectively. The thionicotinamide analogs of NAD and NADP both functioned
      as coenzyme-competitive inhibitors of the enzyme-catalyzed NAD- and NADP-linked
      reactions. A dual wavelength assay, using a combination of NADP and thio-NAD, was
      established and was used to demonstrate that increasing glucose 6-phosphate
      concentration did not change the enzyme preference for the coenzyme form used.
      Sigmoidal relationships were observed for reduction of both dinucleotides, and N
      values were the same as those observed when each dinucleotide was studied as the
      only coenzyme form present in reaction mixtures. Using the dual wavelength assay,
      inhibition by isocitrate, 6-phosphogluconate, ATP, and palmitoyl-CoA was shown to
      be equally effective in both NAD- and NADP-linked reactions. An enzyme activator,
      glucosamine 6-phosphate, altered the glucose 6-phosphate sigmoidicity through
      activation at low substrate concentrations.

PMID- 9252114
TI  - Involvement of the HIV-1 external envelope glycoprotein 120 (gp120) C2 region in
      gp120 oligomerization.
AB  - A synthetic peptide resembling the C2 region of human immunodeficiency virus type
      1 (HIV-1) gp120 (C2-Lai: amino acids (aa) 273-288), inhibited (C50 = 200 microM)
      gp120 calcium-dependent binding of N-acetyl-beta-D-glucosaminyl and mannosyl
      residues exposed on natural glycoprotein bovine fetuin whereas a peptide derived
      from an aa sequence downstream of C2-Lai (C2-SC19) had no such effect (C50 > 1000
      microM). No calcium-carbohydrate-specific binding of C2-Lai to fetuin was
      detected. In addition, C2-Lai was also found to inhibit the calcium-dependent
      oligomerization of gp120: while recombinant gp120 (rgp120) was recovered mainly
      as oligomers (78%) in 10 mM CaCl2, in contrast to 100% monomers in 1mM CaCl2,
      mostly monomers (67%) were found in 10 mM CaCl2 in the presence of C2-Lai.
      Peptide C2-SC19 and carbohydrate structures such as fetuin, fucoidin, dextran or
      mannan did not significantly affect gp120 oligomerization. Electrophoresis and
      gel filtration analysis also showed that C2-Lai aggregated in the form of 20 kDa
      compounds, which is compatible with association of 10 molecules. Taken together,
      these results demonstrate that the C2 domain is involved in gp120 oligomerization
      and suggest that gp120 oligomers but not monomers have specific carbohydrate
      binding properties.

PMID- 9252115
TI  - Jaks, STATs, cytokine signal transduction, and immunoregulation: are we there
      yet?

PMID- 9252116
TI  - Complementation of V(D)J recombination deficiency in RAG-1(-/-) B cells reveals a
      requirement for novel elements in the N-terminus of RAG-1.
AB  - RAG-1 is an essential component of the site-specific V(D)J recombinase. A new
      assay system has revealed a significant contribution of the catalytically
      dispensible N-terminal region of RAG-1 to recombination activity. The foundation
      for this system is an Abelson virus-transformed cell line derived from RAG-1(-/-)
      mice that is dependent on the introduction of exogenous RAG-1 for rearrangement
      of either plasmid substrates or the endogenous immunoglobulin loci. Use of this
      line demonstrates that conserved and novel cysteine-containing elements in the N
      terminal region are required for full RAG-1 activity when recombination activity
      is in a RAG-1 dose-responsive range. Our data suggest that the RAG-1 N-terminus
      enhances the formation of an active recombination complex that facilitates the
      rearrangement process.

PMID- 9252117
TI  - EBF and E47 collaborate to induce expression of the endogenous immunoglobulin
      surrogate light chain genes.
AB  - Early B cell factor (EBF) and E47 participate in the transcriptional control of
      early B lymphocyte differentiation. With the aim of identifying genetic targets
      for these transcription factors, we stably transfected cDNAs encoding EBF or a
      covalent homodimer of E47, individually or together, into immature hematopoietic
      Ba/F3 cells, which lack both factors. In combination, EBF and E47 induce
      efficient expression of the endogenous immunoglobulin surrogate light chain
      genes, lambda5 and VpreB, whereas other pre-B cell-specific genes remain silent.
      Multiple functionally important EBF and E47 binding sites were identified in the
      lambda5 promoter/enhancer region, indicating that lambda5 is a direct genetic
      target for these transcription factors. Taken together, these data suggest that
      EBF and E47 synergize to activate expression of a subset of genes that define an
      early stage of the B cell lineage.

PMID- 9252118
TI  - V(D)J recombination in Ku86-deficient mice: distinct effects on coding, signal,
      and hybrid joint formation.
AB  - Ku, a heterodimer of 70 and 86 kDa subunits, plays a critical but poorly
      understood role in V(D)J recombination. Although Ku86-deficient mice are
      defective in coding and signal joint formation, rare recombination products have
      been detected by PCR. Here, we report nucleotide sequences of 99 junctions from
      Ku86-deficient mice. Over 90% of the coding joints, but not signal or hybrid
      joints, exhibit short sequence homologies, indicating that homology is required
      to join coding ends in the absence of Ku86. Our results suggest that Ku86 may
      normally have distinct functions in the formation of these different types of
      junctions. Furthermore, Ku86(-/-) joints are unexpectedly devoid of N-region
      diversity, suggesting a novel role for Ku in the addition of N nucleotides by
      terminal deoxynucleotidyl transferase.

PMID- 9252119
TI  - Fc gammaRIIB1 inhibition of BCR-mediated phosphoinositide hydrolysis and Ca2+
      mobilization is integrated by CD19 dephosphorylation.
AB  - The B cell receptor for immunoglobulin G, Fc gammaRIIB1, is a potent transducer
      of signals that block antigen-induced B cell activation. Coligation of Fc
      gammaRIIB1 with B lymphocyte antigen receptors (BCR) causes premature termination
      of phosphoinositide hydrolysis and Ca2+ mobilization and inhibits proliferation.
      This inhibitory signal is mediated in part by phosphorylation of Fc gammaRIIB1
      and recruitment of phosphatases; however, the molecular target(s) of effectors is
      unknown. Here we report that Fc gammaRIIB1 inhibition of BCR signaling is
      mediated in part by selective dephosphorylation of CD19, a BCR accessory molecule
      and coreceptor. CD19 dephosphorylation leads to failed CD19 association with
      phosphatidylinositol 3-kinase, and this in turn leads to termination of inositol
      1,4,5-trisphosphate production, intracellular Ca2+ release, and Ca2+ influx. The
      results define a molecular circuit by which Fc gammaRIIB signals block
      phosphoinositide hydrolysis.

PMID- 9252120
TI  - Counterregulation by the coreceptors CD19 and CD22 of MAP kinase activation by
      membrane immunoglobulin.
AB  - The signaling pathways linked to membrane immunoglobulin (mIg) that are regulated
      by the coreceptors CD19 and CD22 are not known. The mitogen-activated protein
      (MAP) kinases ERK2, JNK, and p38 couple extracellular signals to transcriptional
      responses. The capacity of mIg to activate these MAP kinases is synergistically
      amplified by coligating CD19, and this effect requires that CD19 be juxtaposed to
      mIg. CD22 suppresses MAP kinase activation when cross-linked to mIg alone or to
      the coligated complex of mIg and CD19. Separate ligation and sequestration of
      CD22 from mIg enhances MAP kinase activation, probably reflecting release of mIg
      from constitutive down-regulation. Thus, CD19 and CD22 have counterregulatory
      effects on MAP kinase activation by mIg, which are dependent on their proximity
      to the antigen receptor.

PMID- 9252121
TI  - Characterization of the B lymphocyte populations in Lyn-deficient mice and the
      role of Lyn in signal initiation and down-regulation.
AB  - Lyn-deficient mice were generated to analyze the role of Lyn in B cell antigen
      receptor (BCR) signaling. These mice had a reduced number of peripheral B cells
      with a greater proportion of immature cells and a higher than normal turnover
      rate. Aged lyn-/- mice developed splenomegaly, produced autoantibodies, and had
      an expanded population of B lymphoblasts of the B1 lineage. Splenic B cells from
      young lyn-/- mice initiated early BCR signaling events, although in a delayed
      fashion. Unexpectedly, lyn-/- B cells exhibited an enhanced MAP kinase activation
      and an increased proliferative response to BCR engagement. Stimulation of lyn-/-
      B cells with intact and F(ab')2 anti-IgM revealed defects in at least two
      mechanisms that negatively regulate BCR signaling, one of which involves Fc
      gammaRIIb1.

PMID- 9252122
TI  - Intrathymic delta selection events in gammadelta cell development.
AB  - The major pathway of gammadelta cell development is shown to be regulated by in
      frame rearrangements at the T cell receptor (TCR) delta locus. Such "delta
      selection" occurs at or around the same point in thymocyte development as
      selection for in-frame rearrangements at the TCRbeta locus. However, there are at
      least two major differences with beta selection: first, delta selection commonly
      involves selection on the cognate TCR chain, gamma, suggesting that there is no
      "preTgamma" chain of major biological significance; second, most gammadelta
      selected thymocytes differentiate rather than proliferate. Nonetheless, some
      delta selection events seemingly facilitate thymocyte expansion, similar to
      alphabeta T cell development. In these cases, TCRgamma selection is less obvious.
      Furthermore, the capacity of individual gamma chains to facilitate gammadelta
      selection is shown to vary with developmental age. The results further clarify
      early T cell development at the beta selection/delta selection stage and place
      clear constraints on models of cell fate determination.

PMID- 9252123
TI  - Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple
      HLA-A and HLA-B supertype alleles.
AB  - We recently described human leukocyte antigen (HLA) A2, A3 and B7 supertypes,
      characterized by largely overlapping peptide-binding specificities and
      represented in a high percentage of different populations. Here, we identified 17
      Plasmodium falciparum peptides capable of binding these supertypes and assessed
      antigenicity in both vaccinated and naturally exposed populations. Positive
      cytotoxic T lymphocyte recall and cytokine (interferon-gamma and tumor necrosis
      factor alpha) responses were detected for all peptides; all were recognized in
      the context of more than one HLA class I molecule; and at least 12 of the 17 were
      recognized in the context of all HLA alleles studied. These data validate the
      concept of HLA supertypes at the biological level, show that highly degenerate
      peptides are almost always recognized as epitopes, and demonstrate the
      feasibility of developing a universally effective vaccine by focusing on a
      limited number of peptide specificities.

PMID- 9252124
TI  - The alpha chain of the T cell antigen receptor is degraded in the cytosol.
AB  - To reach the cell surface, the T cell receptor for antigen (TCR)-CD3 complex must
      assemble in the endoplasmic reticulum (ER), where single subunits are retained
      and degraded. However, the exact location of breakdown and the mechanism and
      proteases involved in destruction of free subunits have remained elusive. We show
      that degradation of the TCR alpha chain is impaired in the presence of
      lactacystin and carboxybenzyl-leucyl-leucyl-leucinal, two inhibitors for
      proteasomal proteolysis. We identified breakdown intermediates that were either
      soluble, cytosolic, and devoid of N-linked glycans, or membrane-associated and
      partially deglycosylated by cytosolic N-glycanase. Protease protection
      experiments showed a cytosolic disposition of these membrane-associated
      intermediates. Combined, these results argue for a cytosolic degradation route of
      the TCR alpha chain involving dislocation from the ER, followed by cytosolic
      deglycosylation and proteolysis by the proteasome.

PMID- 9252125
TI  - Targeted complementation of MHC class II deficiency by intrathymic delivery of
      recombinant adenoviruses.
AB  - De novo differentiation of CD4+ T cells was provoked in mice lacking major
      histocompatibility complex (MHC) class II molecules by intrathymic injection of
      adenovirus vectors carrying class II genes. This permits a new approach to
      questions concerning the dynamics of CD4+ T cell compartments in the thymus and
      peripheral lymphoid organs. Here two issues are explored. First, we show that
      mature CD4+ CD8- cells reside in the thymus for a protracted period before
      emigrating to the periphery, highlighting the potential importance of, and our
      ignorance of, the postselection maturation period. Second, we demonstrate that
      the survival of CD4+ cells in peripheral lymphoid organs is markedly curtailed
      when class II molecules are absent and is not further reduced in the absence of
      both class II and class I molecules, raising the possibility that MHC-mediated
      selection may continue in the periphery.

PMID- 9252126
TI  - The role of mel-18, a mammalian Polycomb group gene, during IL-7-dependent
      proliferation of lymphocyte precursors.
AB  - mel-18 is a mammalian homolog of Drosophila melanogaster Polycomb group genes.
      Mice lacking the mel-18 gene show a posterior transformation of the axial
      skeleton, severe combined immunodeficiency, and a food-passing disturbance in the
      lower intestine due to hypertrophy of the smooth muscle layer. In this study, the
      severe combined immunodeficiency observed in mel-18 mutant mice is correlated
      with the impaired mitotic response of lymphocyte precursors upon interleukin-7
      stimulation. Strikingly, the axial skeleton and lymphoid phenotypes are identical
      in both mel-18 and bmi-1 mutants, indicating that the Mel-18 and Bmi-1 gene
      products might act in the same genetic cascade. These results suggest that
      mammalian Polycomb group gene products are involved in cell cycle progression in
      the immune system.

PMID- 9252127
TI  - The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and
      normal cell cycle progression.
AB  - Interleukin-7 (IL-7)-deficient mice exhibit an early defect in lymphopoiesis. We
      examined Bcl-2 expression and the cell cycle status of immature thymocyte subsets
      in these mice. In IL-7-deficient mice, developmental transition to a T cell
      committed fate was accompanied by a striking loss of Bcl-2 protein expression and
      an increased relative proportion of cells in the G0/G1 stage of the cell cycle.
      Short-term culture of immature thymocytes with rIL-7 caused up-regulation of Bcl
      2 protein and cell survival. These data specify a T cell lineage developmental
      transition point, prior to T cell antigen receptor rearrangement, where IL-7
      signal transduction is linked to an anti-apoptosis mechanism and the cell cycle.

PMID- 9252128
TI  - Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma
      chain-deficient mice.
AB  - The common cytokine receptor gamma chain (gamma(c)) is an indispensable subunit
      for the formation of lymphoid-related cytokine receptors, including IL-7 and IL
      15 receptors, that mediate nonredundant or critical signals for the
      differentiation of T and B cells and natural killer (NK) cells, respectively. We
      introduced the bcl-2 transgene driven by E mu or H-2K promoters into gamma(c)
      deficient mice that lack all three lymphoid subclasses. The forced expression of
      Bcl-2 restored all stages of T lymphopoiesis, but not B or NK cell development,
      indicating that a primary function of gamma(c)-mediated signals in the T lineage
      might be to maintain cell survival. Therefore, the development of T, B, and NK
      cells may be influenced by distinct intracytoplasmic signaling cascades that are
      activated by coupling of gamma(c)-related receptors.

PMID- 9252129
TI  - Different functions of the GTPase Rho in prothymocytes and late pre-T cells.
AB  - Mice lacking thymic function of the GTPase Rho show severe defects in fetal and
      adult thymopoiesis. Rho thymi are deficient in CD44+ CD25+ pro-T cells and CD44-
      CD25+ early pre-T cells because Rho function is required for survival but not
      G1/S phase cell cycle progression in these populations. The selective apoptosis
      defect in Rho prothymocytes can be rescued by expression of a bcl-2 transgene. A
      second function for Rho is seen in CD44- CD25- late pre-T cells: Rho regulates
      cell cycle progression but not survival of this population. These studies show
      that the critical processes of proliferation and survival are independently
      regulated during thymopoiesis and establish two different functions for Rho in
      the development of early thymic progenitors.

PMID- 9252130
TI  - Gene therapy for chronic viral hepatitis: ribozymes, antisense oligonucleotides,
      and dominant negative mutants.

PMID- 9252131
TI  - Inhibition of pancreaticobiliary secretion by loperamide in humans.
AB  - Loperamide, a peripherally acting opiate receptor agonist with antidiarrheal
      action, inhibits ileal and colonic motor function. It was determined whether
      loperamide also affects gallbladder emptying and pancreatic enzyme secretion in
      humans. Plasma cholecystokinin (radioimmunoassay), gallbladder volume
      (ultrasonography), and intraduodenal bilirubin and amylase output (spot sampling)
      were measured at regular intervals before and during intraduodenal perfusion of
      an amino acid meal in 8 healthy subjects: once without and once with pretreatment
      of 8 mg loperamide, ingested 13 and 4 hours before the start of the meal.
      Loperamide decreased basal amylase output from 3.2 +/- 0.5 to 1.0 +/- 0.5 kU/h (P
      < .005) and abolished basal bilirubin output (21 +/- 5 vs. 0 +/- 0 micromol/h; P
      < .005) into the duodenum. Loperamide increased basal gallbladder volume from 28
      +/- 4 to 39 +/- 4 mL (P < .0001) but was without effect on basal plasma
      cholecystokinin (2.7 +/- 0.3 vs. 3.0 +/- 0.3 pmol/L). During the amino acid meal,
      pretreatment with loperamide inhibited amylase output from 5.1 +/- 0.8 to 1.6 +/-
      0.4 kU/h (P < .001), bilirubin output from 39 +/- 6 to 18 +/- 6 micromol/h (P <
      .0005) and gallbladder contraction from 47% +/- 3% to 26% +/- 6% (P < .05),
      whereas loperamide enhanced amino acid-stimulated plasma cholecystokinin from 4.5
      +/- 1.6 to 7.6 +/- 1.0 pmol/L (P < .05). It is concluded that loperamide inhibits
      basal and amino acid-stimulated gallbladder motility and intraduodenal output of
      bilirubin and amylase, despite an enhanced postprandial cholecystokinin release.

PMID- 9252132
TI  - Circulatory effects of graded diversion of portal blood flow to the systemic
      circulation in rats: role of nitric oxide.
AB  - Total portal-systemic shunting in normal animals is associated with splanchnic
      and systemic vasodilation, suggesting that vasodilation in cirrhosis may be
      facilitated by spontaneous shunts promoted by portal hypertension. However, the
      mechanism of this vasodilation is unknown. The aim is to study the acute effects
      of the graded diversion of portal blood flow to the systemic circulation in
      normal and portal hypertensive rats. Portal and systemic hemodynamics were
      measured in normal and portal hypertensive rats before and during graded
      portacaval diversion of portal blood flow, in basal conditions, and after nitric
      oxide inhibition. In portal hypertensive rats, graded portal flow diversion
      caused a rate-related decrease in portal pressure (from 15.3 +/- 0.6 to 11.2 +/-
      0.7 mm hg at 6 mL x min(-1), P < .001) and a redistribution of portal-collateral
      blood flow from the spontaneous portal-systemic collaterals to the portacaval
      circuit, without changing total portal-systemic shunting. Graded portal diversion
      caused an immediate systemic vasodilation, with reduced peripheral resistance.
      This vasodilatory response was more pronounced in normal than in portal
      hypertensive rats (increase in cardiac index 23.6% +/- 2.8% vs. 8.5% +/- 4.9%, P
      < .02, fall in peripheral resistance -24.5% +/- 3.4% vs. -16.5% +/- 2.6%, P =
      .08), and was totally prevented by nitric oxide inhibition. The graded diversion
      of portal blood flow caused a flow-rate-related reduction in portal pressure and
      blood flow through spontaneous portal-systemic collaterals in portal hypertensive
      rats, and caused a nitric-oxide dependent systemic vasodilatory response, which
      was greater in normal than in portal hypertensive rats. These results suggest
      that portal-systemic shunting per se may contribute to the vasodilatation in
      portal hypertension.

PMID- 9252133
TI  - Elevated glomerular and blood mononuclear lymphocyte nitric oxide production in
      rats with chronic bile duct ligation: role of inducible nitric oxide synthase
      activation.
AB  - Recent work indicates that nitric oxide (NO) plays an important role in the
      systemic and renal alterations of cirrhosis. In the present study, we have
      evaluated whether the inducible NO synthase (iNOS) isoform participates in the
      enhanced renal and systemic NO production of a rat model of cirrhosis. In vitro
      and in vivo experiments were performed in rats subjected to chronic bile duct
      ligation (BDL) and in sham-operated (SO) animals. Plasma nitrite (3.1 +/- 0.1
      micromol/L in SO and 6.6 +/- 0.2 micromol/L in BDL), glomerular nitrite
      production (6.4 +/- 0.1 vs. 9.8 +/- 0.1 nmol/24h/7,000 glomeruli, respectively),
      and mononuclear lymphocyte cells nitrite production (0.3 +/- 0.04 vs. 0.6 +/-
      0.12 nmol/10(6) cells, respectively) were all significantly higher in BDL than in
      SO. Moreover, mononuclear lymphocytes and glomeruli from BDL rats showed an
      increased expression of macrophage-type iNOS, detected by Western blot. Kidneys
      from BDL animals also showed an increased calcium-independent NO synthase
      activity, compared with those from SO rats. Constitutive endothelial-type NO
      synthase expression in glomeruli or the activity of calcium-dependent NO synthase
      in whole kidney did not show differences between BDL and SO rats. In cultured
      mesangial cells from normal rats, the addition of plasma from BDL but not of
      plasma from SO significantly stimulated (35%) nitrite production and increased
      the expression of macrophage-type iNOS. In addition, administration of
      aminoguanidine (AG), a preferential iNOS inhibitor, elevated dose-dependently
      mean arterial pressure in both groups, but this increase was greater in BDL (26.5
      +/- 4.4 mm hg) than in SO (13.6 +/- 2.6). In BDL, AG also increased sodium and
      water excretion and glomerular filtration rate. In contrast, there were only
      small nonsignificant changes in SO animals. Therefore, these results indicate
      that the expression, activity and production of NO in kidneys, glomeruli, and
      mononuclear lymphocyte cells is elevated in BDL rats, and this is partly because
      of a plasma-derived substance(s), which stimulates iNOS formation. The
      amelioration of the arterial hypotension and the associated reduced excretory
      levels of these cirrhotic animals by aminoguanidine further support the
      involvement of the inducible NO synthase isoform in the renal alterations
      observed in BDL animals.

PMID- 9252134
TI  - Cerebral benzodiazepine receptor binding in vivo in patients with recurrent
      hepatic encephalopathy.
AB  - Increased activation of the central benzodiazepine receptor (BZR) appears to play
      an important role in hepatic encephalopathy (HE). However, there is controversy
      regarding whether the density or affinity of BZRs is altered. A previous positron
      emission tomography (PET) study using the BZR antagonist [11C]flumazenil (FMZ)
      found two- to threefold greater cerebral cortical tracer uptake in recurrent HE,
      but did not account for impaired FMZ metabolism due to liver disease or assess
      the relative contributions of tracer delivery versus BZR binding. We hypothesized
      that correcting for these factors would affect estimations of BZR binding in HE.
      Nine patients with recurrent HE and 13 age-comparable controls were studied with
      [11C]FMZ PET. After intravenous administration of [11C]FMZ, arterial blood
      samples were collected, and PET images were acquired over 60 minutes. FMZ
      transport and binding maps were calculated for each subject by using a
      physiological tracer kinetic model. In agreement with the previous report, we
      found that FMZ reached a much higher level and was retained longer in the HE
      cerebral cortex despite similar total blood radioactivity levels in the two
      groups. However, the patients showed impaired hepatic metabolism of FMZ. After
      physiological modeling incorporating these data, significant increases in BZR
      binding were found in the thalamus (13%), cerebellum (20%), and pons (23%). There
      were minor, statistically insignificant increases in cerebral cortical (10%),
      putamen (12%), and whole brain (12%) BZR binding in patients with recurrent HE.
      These findings are in general agreement with results of autopsy studies,
      confirming a lack of major increases in cortical or basal ganglial BZR binding in
      HE. They emphasize that physiological tracer modeling should be used and altered
      peripheral radioligand metabolism considered in future PET studies of HE.

PMID- 9252135
TI  - Factors regulating tumor pressure in hepatocellular carcinoma and implications
      for tumor spread.
AB  - This study was performed to investigate factors determining tumor pressure (TP)
      in hepatocellular carcinoma (HCC) and a correlation of pressure gradient between
      TP and portal vein pressure (PVP) with tumor spread. TP and hepatic tissue
      pressure (HTP) were measured in 70 patients who underwent hepatic resection for
      HCC. Changes in TP after hepatic artery occlusion (HAO) or portal vein occlusion
      (PVO) were observed. HTP was elevated with worsening chronic liver disease, and
      exhibited a significant positive correlation with PVP. The TP was significantly
      higher in the encapsulated and the nonnecrotic HCCs. The pressure gradient (TP
      PVP) was significantly greater in the encapsulated HCCs, especially in those with
      microscopic portal vein invasion (vp) or intrahepatic metastasis (im). HAO caused
      a greater decrease in TP than did PVO, with the decrease being particularly
      marked in the encapsulated HCCs. The TP of HCC was found to be regulated mainly
      by the presence or absence of a tumor capsule or necrosis, and partly by the
      hepatic arterial flow and PVP. Our study suggests that TP increases with capsule
      formation and that the pressure gradient between TP and PVP may be a causal
      factor in the dispersement of tumor cells into the portal vein.

PMID- 9252136
TI  - Hepatocytic phenotypes induced in sarcomatous cholangiocarcinoma cells treated
      with 5-azacytidine.
AB  - The sarcomatoid cells found in cholangiocarcinoma (CC) or hepatocellular
      carcinoma (HCC) are not well characterized. In this study, a human sarcomatoid CC
      cell line, ETK-1, was established from a patient, and then morphological and
      phenotypical characteristics of the ETK-1 cells were evaluated before and after
      treatment with differentiation-inducing 5-azacytidine (5-azaCR). Phenotypically,
      the ETK-1 cells appeared immature. Exposure to 5-azaCR induced morphological
      transformation; a converted cell line, MEK, was successfully established. The MEK
      cells expressed such hepatocyte-specific proteins as alpha-fetoprotein, albumin,
      integrin alpha1, and thrombopoietin, but lost such bile duct-specific proteins as
      integrin alpha3 and integrin beta4. The histopathology of MEK xenografts
      resembled that of HCC. The ETK-1 cells appeared to be converted into hepatocytes
      by exposure to 5-azaCR. On the other hand, ETK-1 xenografts were diagnosed as
      tubular adenocarcinoma, and the tumor cells had a ductal phenotype. This suggests
      the possibility that ETK-1 cells can differentiate along a biliary epithelial
      cell lineage. ETK-1 and MEK will be useful in studying hepatocytic
      differentiation and the transformation from a biliary epithelial cell to a
      hepatocytic lineage.

PMID- 9252137
TI  - Possible involvement of pertussis toxin-sensitive G protein in hepatocyte growth
      factor-induced signal transduction in cultured rat hepatocytes: pertussis toxin
      treatment inhibits activation of phospholipid signaling, calcium oscillation, and
      mitogen-activated protein kinase.
AB  - Treatment of primary cultured rat hepatocytes with hepatocyte growth factor (HGF)
      gives rise to inositol phosphate formation, cytosolic calcium oscillation,
      activation of mitogen-activated protein (MAP) kinase and phospholipase D (PLD),
      and arachidonic acid release, leading to DNA synthesis. Pretreatment of cultured
      hepatocytes with pertussis toxin (PT), which is known to adenosine diphosphate
      ribosylate Gi and Go guanine nucleotide -binding proteins and to inhibit their
      functions, partially inhibited HGF-induced [3H]thymidine incorporation in a
      concentration-dependent manner. These results suggest that HGF-mediated DNA
      synthesis of hepatocytes is partly regulated via PT-sensitive guanine nucleotide
      binding protein. Therefore, the effects of PT treatment on HGF-induced signal
      transduction pathways were investigated. HGF-induced MAP kinase activation and
      arachidonic acid release were decreased by PT treatment, whereas PLD activation
      was diminished by PT to the level of unstimulated control. PT also interfered
      with HGF-induced inositol phosphate formation and cytosolic calcium oscillation.
      These results suggest that both PT-sensitive and PT-insensitive pathways are
      involved in HGF-induced signaling.

PMID- 9252138
TI  - Mouse liver T cells: their change with aging and in comparison with peripheral T
      cells.
AB  - Mouse liver contains both IL-2Rbeta- (or low positive) high T-cell receptor
      (TCR(hi)) cells and IL-2Rbeta+ intermediate TCR (TCR(int)) cells. TCR(int) cells
      consist of natural killer 1.1 (NK1)+ and NK1- subsets. NK1- TCR(int) cells
      increase constantly with age whereas TCR(hi) cells decrease. NK1+ TCR(int) cell
      proportions in the liver increase until middle age and decrease thereafter.
      Although NK1+ TCR(int) cells in other organs are few regardless of age, NK1-
      TCR(int) cells gradually appear in other lymphoid organs with aging. Skewed usage
      of Vbeta7 and Vbeta8 TCR was observed in NK1+ TCR(int) cells in the liver but the
      predominance was less obvious in NK1- TCR(int) and TCR(hi) cells in the liver and
      other organs. TCR V alpha14 messenger RNA (mRNA) was detected in NK1+ TCR(int)
      cells but not in the other two populations. In contrast, although NK1+ TCR(int)
      cells contain virtually no V alpha11+ T cells, NK1- TCR(int) cells contain a much
      higher proportion (approximately 12%) of V alpha11+ T cells, whereas
      approximately 4% of TCR(hi) cells are V alpha11+. NK activities of liver
      mononuclear cells (MNC) and splenocytes decrease with aging, although the former
      is always greater than the latter. NK activity of liver MNC is a function of NK
      cells, partly NK1+ TCR(int) cells but not NK1- TCR(int) cells or TCR(hi) cells.
      These results suggest that lymphocytes of liver and other organs at old age are
      no longer occupied solely by conventional thymus-derived T cells, and the
      increase of extrathymic IL-2Rbeta+ NK1- TCR(int) cells in liver and periphery
      could be closely related to immunological changes with aging.

PMID- 9252139
TI  - Hepatic stellate cell immunodetection and cirrhotic evolution of viral hepatitis
      in liver allografts.
AB  - Patients with chronic viral hepatitis are at high risk of developing cirrhosis,
      but the outcome of the disease in a given patient is unpredictable. Hepatic
      stellate cells have been demonstrated to be the most important cell type involved
      in hepatic fibrogenesis, regardless of the cause of the liver injury. The alpha
      isotype of actin (a phenotypic marker of smooth muscle cells) may be expressed by
      hepatic stellate cells, reflecting their "activation" to myofibroblast-like
      cells. The present study aimed to analyze the expression of alpha-smooth muscle
      actin-positive hepatic stellate cells in liver allografts with recurrent viral
      hepatitis, and to evaluate whether and how such expression may be related to the
      outcome of the disease. Using immunohistochemistry and a semi-quantitative
      scoring system, the expression of a-smooth muscle actin in hepatic stellate cells
      was analyzed in liver allografts of 17 patients with recurrent viral hepatitis.
      They included nine patients who developed cirrhosis at the end of follow-up (mean
      time 23.6 months), and eight patients with no cirrhosis at the end of a
      comparable follow-up time (mean 30.1 months). In all patients, liver biopsy
      specimens were obtained between 3 and 6 months (t1) and between 10 and 15 months
      (t2) after transplantation. Preperfusion biopsy specimens of donor livers served
      as a baseline (t0). By comparison with the baseline biopsy, an increased number
      of alpha-smooth muscle actin-expressing hepatic stellate cells was observed in
      all cases in t1 biopsies. An increase in the amount of alpha-smooth muscle actin
      positive hepatic stellate cells in zone 1 at t1 was significantly (P < .006)
      related to subsequent cirrhotic evolution. In conclusion, in liver allografts
      with recurrent viral hepatitis, the activation of hepatic stellate cells is an
      early event. An increased number of alpha-smooth muscle actin-positive hepatic
      stellate cells in zone 1 may represent an unfavorable event related to cirrhotic
      evolution.

PMID- 9252140
TI  - Pentoxifylline inhibits growth and collagen synthesis of cultured human hepatic
      myofibroblast-like cells.
AB  - During the course of liver fibrogenesis, myofibroblast-like cells (MFLC), mostly
      derived from hepatic stellate cells, proliferate and synthesize excessive amounts
      of extracellular matrix components. Pentoxifylline (PTX) elicits
      antiproliferative and antifibrogenic effects in human dermal fibroblasts. The aim
      of this study was to test the effects of PTX on the proliferation and the
      synthesis of collagen and gelatinase A in cultured human hepatic MFLC. MFLC were
      obtained by outgrowth from human liver explants. PTX markedly reduced serum
      driven cell proliferation, as assessed by nuclear autoradiography experiments and
      measurement of actual cell growth. Growth inhibition was totally reversed after
      removal of the drug. PTX also affected collagen synthesis, as measured by
      [3H]hydroxyproline incorporation into proteins. Synthesis of secreted collagen
      was reduced by 24% and 67% at concentrations of 100 microg/mL and 500 microg/mL,
      respectively. This was associated with a decrease in type I and III procollagen
      messenger RNA (mRNA), indicating an effect at a pretranslational level. In
      contrast, PTX did not affect either gelatinase A activity released in culture
      medium or the expression of its specific mRNA. In conclusion, PTX exhibits potent
      antiproliferative and antifibrogenic effects toward hepatic MFLC. These results
      suggest that PTX might have therapeutic implications in chronic liver disease.

PMID- 9252141
TI  - Cell growth and differentiation of a novel mouse Ito (fat-storing) cell line
      transformed by a temperature-sensitive mutant of simian virus 40.
AB  - A novel mouse Ito (fat-storing) cell line (A640-IS) was established by
      transformation with a temperature-sensitive mutant of simian virus 40 (SV40) and
      the relationships between the expression of SV40 large T antigen and the growth,
      differentiation, and functions of A640-IS cells were investigated. A640-IS cells
      expressed large T antigen when cultured at 33 degrees C. At this temperature, the
      cells grew actively, assumed a fibroblastic shape, and showed few Ito cell
      characteristics. In contrast, when large T-antigen expression was inhibited by
      culture at 39 degrees C, the cells did not grow but differentiated into Ito cells
      as assessed by both morphological and functional characteristics. Expression of
      the transcription factor SCL (stem cell leukemia), which plays a role in the
      development and differentiation of blood cells, was observed at both 33 degrees C
      and 39 degrees C, although expression was greater at 33 degrees C. Therefore,
      opposite patterns of cell growth and the functions of differentiated cells
      occurred at 33 degrees C and 39 degrees C in this novel Ito cell line.
      Transforming growth factor beta1 stimulated A640-IS cells to produce fibronectin,
      collagen type III, and laminin. This unique Ito cell line provides a useful model
      to address important questions regarding the nature of these cells.

PMID- 9252142
TI  - S-adenosyl-L-methionine protects the liver against the cholestatic, cytotoxic,
      and vasoactive effects of leukotriene D4: a study with isolated and perfused rat
      liver.
AB  - Cysteinyl-leukotrienes can cause cholestasis and liver damage when administered
      at nanomolar concentrations. Using the isolated and perfused rat liver we
      analyzed whether S-adenosyl-L-methionine (SAMe) may protect this organ against
      the noxious effects of leukotriene-D4 (LTD4). We observed that a 2 nmol bolus of
      this compound decreased bile flow (-12.6% +/- 1.6%, P < .02), and bile salt
      excretion (-23.5% +/- 2.2%, P < .02; both compared with baseline values), caused
      the release of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase
      (LDH) to the hepatic effluent, and increased significantly the perfusion pressure
      as compared with a control group not receiving LTD4 (6.0 +/- 1.1 vs. 0.2 +/- 0.02
      mm hg, respectively; P < .001). The cholestatic effect of LTD4 was attenuated by
      infusion of SAMe which, at rates of 67 and 100 microg/min, totally prevented the
      decrease in bile salt excretion. Likewise, in SAMe infused livers, the release to
      the effluent of GOT and LDH was lower than in the group receiving LTD4 only, and
      was even lower than in the control group. We also found that the increase in
      perfusion pressure induced by LTD4 was prevented by SAMe in a dose-dependent
      manner. Of interest, SAMe increased the biliary excretion of the eicosanoid in a
      dose-related fashion. We conclude that SAMe reverts the cholestatic, cytotoxic,
      and hemodynamic effects of LTD4 on the liver, and that these protective effects
      might be partly because of a stimulation of the biliary excretion of the
      leukotriene.

PMID- 9252143
TI  - Role of nitric oxide in oxygen transport in rat liver sinusoids during
      endotoxemia.
AB  - To evaluate the role of nitric oxide (NO) in hepatic microcirculation and liver
      injury during endotoxemia, we studied O2 transport in the hepatic
      microcirculation of endotoxin-infused rats. Rats were continuously infused with
      Escherichia coli lipopolysaccharide (LPS) (0.8 mg/kg/h) for 7 hours. LPS
      increased the plasma levels of NO2- + NO3- and aspartate transaminase (AST), and
      decreased the bile flow rate and hepatic adenosine triphosphate (ATP) level.
      Hepatic microcirculation was evaluated by two methods: reflectance
      spectrophotometry showed a decrease in the oxygenation of hemoglobin (Hb) in the
      liver, and dual-spot microspectroscopy indicated that LPS administration
      decreased blood velocity, the oxygenation of Hb, and O2 release from sinusoids to
      hepatocytes. The observed decreases in the O2 transport parameters were prominent
      in pericentral sinusoids. All of these phenomena were further aggravated by the
      administration of N(w)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg/h) plus
      LPS, and by aminoguanidine (AMG) (5 mg/kg/h) plus LPS, and these could be
      reversed by the concomitant administration of L-arginine (L-Arg) (100 mg/kg/h).
      These results suggest that deterioration of hepatic oxygen transport and liver
      function induced by endotoxin can be ameliorated by NO.

PMID- 9252144
TI  - Role of ischemia in causing apoptosis, atrophy, and nodular hyperplasia in human
      liver.
AB  - Ischemia is known to be a cause of hepatocellular apoptosis and atrophy in
      experimental animals, but the effect of vascular obstruction on such lesions in
      the normal or cirrhotic human liver has not been studied. The purpose of this
      study was to investigate the role of ischemia in the development of apoptosis,
      atrophy, and nodular hyperplasia in cirrhotic and noncirrhotic human livers.
      Apoptosis, focal atrophy, and nodular hyperplasia were semiquantitated in 203
      liver specimens obtained at transplantation, segmental resection, or autopsy.
      These parameters were correlated with etiology, stage, activity, and acute and
      healed portal vein thrombosis (PVT). Large numbers of apoptotic cells were found
      in livers with acute PVT (17.2/medium-power field [MPF]) and in infarcts of Zahn
      caused by obstruction of portal veins (PVs) by tumor (16.4/MPF). Smaller numbers
      of apoptotic cells were found in cirrhosis of various etiologies (3.8-10.0/MPF)
      and rarely in normal livers (0.16/MPF). Evidence of healed PVT was found in 47%
      of cirrhotic livers and was associated with nodular hyperplasia (58% vs. 32%, P <
      .01) and focal atrophy (79% vs. 49%, P < .002). Apoptotic cells were found
      equally in those with and without healed PVT (40% vs. 38%, not significant).
      These observations suggest that apoptosis is a transient response to acute
      ischemia and that atrophy and nodular hyperplasia are chronic responses to
      ischemia. Vascular obstruction may be an important cause of the apoptosis and
      atrophy, which are found in nodular regenerative hyperplasia (NRH), infarct of
      Zahn, chronic hepatitis, and cirrhosis.

PMID- 9252145
TI  - Oxygen-free radical-mediated injury to cultured rat hepatocytes during cold
      incubation in preservation solutions.
AB  - We have previously shown that the injury to cultured liver endothelial cells
      during cold incubation in University of Wisconsin (UW) solution is energy
      dependent and is mediated by reactive oxygen species. Here we demonstrate that
      this reactive oxygen-mediated injury is specific neither to endothelial cells nor
      to UW solution: cultured hepatocytes incubated in cold (4 degrees C) UW solution
      or histidine-tryptophan-ketoglutarate (HTK) solution were injured under normoxic
      conditions (loss of viability, 63% +/- 10% after 48 hours of cold incubation in
      UW solution and 82% +/- 11% after 24 hours of cold incubation in HTK solution),
      whereas hypoxia was protective (loss of viability, 29% +/- 12% [UW] and 13% +/-
      3% [HTK] after the same cold incubation times). The injury under normoxic
      conditions was also largely decreased by adding either the spin trap 5,5-dimethyl
      1-pyrroline N-oxide (DMPO) or the flavonoid silibinin to the solutions, or by
      preincubating the cells with the iron chelator deferoxamine before the
      hypothermic incubation. Marked lipid peroxidation was observed during cold
      incubation in both preservation solutions. These results suggest that the injury
      to cultured hepatocytes during cold incubation in UW and HTK solutions is
      mediated by reactive oxygen species as is the injury to cultured liver
      endothelial cells.

PMID- 9252146
TI  - Intrahepatic cholestasis of pregnancy: a French prospective study.
AB  - The aim of this prospective study was to analyze the characteristics of
      intrahepatic cholestasis of pregnancy (ICP) in a French population. From 1989 to
      1995 we studied 50 consecutive pregnant women with ICP (41 single, 7 twin, and 2
      triplet pregnancies) referred for hepatologic consultation. All patients suffered
      from pruritus and/or jaundice associated with elevated fasting serum levels of
      total bile acids (mean 49 micromol/L, range 7-290). No patients had concomitant
      liver disease and all recovered normal liver function after delivery. Overall
      prematurity rate was 60%: 100% in multiple pregnancies and 41% in single
      pregnancies. Three of 61 babies died. Systematic clinical interviews revealed
      that 34 patients had been treated with oral micronized natural progesterone (200
      1,000 mg/d) during the current pregnancy for risk of premature delivery,
      including at least 32 (64%) before the onset of pruritus. Onset of pruritus was
      statistically earlier in patients previously receiving progesterone than in
      patients not receiving progesterone (217 +/- 21 vs. 240 +/- 26 days, P < .01).
      This was also found in the single pregnancy subgroup of patients (222 +/- 19 vs.
      240 +/- 26 days, P < .05). Pruritus disappeared before delivery in 10 of 50
      patients, i.e., after withdrawal of progesterone in 7 patients (only one
      concurrently treated with cholestyramine), after decrease in dose of progesterone
      in 1 patient, and spontaneously in 2 patients. During the same period, the
      percentage of pregnant women without ICP who had been treated with progesterone
      during pregnancy was statistically lower than the percentage of patients treated
      with progesterone before the onset of pruritus in our group of patients with ICP
      (36% vs. 64%, P < .01, odds ratio 3.16, 95% CI:1.29-7.80). These results suggest
      that orally administered progesterone might be an exogenous factor which triggers
      ICP in predisposed women.

PMID- 9252147
TI  - Focal glycogenosis of the liver in disorders of ureagenesis: its occurrence and
      diagnostic significance.
AB  - Metabolic disorders of ureagenesis can cause a Reye-like syndrome with
      potentially fatal hyperammonemia in children. A mechanistically heterogeneous
      subset of these disorders shares the biochemical end-result of impaired
      mitochondrial citrulline production. These include deficiencies of the
      mitochondrial enzymes, ornithine transcarbamylase (OTC) and carbamyl-phosphate
      synthase (CPS), as well as dibasic aminoacidurias hyperammonemia
      hyperornithinemia-homocitrullinuria (HHH) and lysinuric protein intolerance
      (LPI). In this report, we present histopathology of the liver in 10 children with
      defects of ureagenesis, including 6 with OTC deficiency, 3 with CPS deficiency,
      and 1 with HHH. The liver showed diffuse microvesicular steatosis, marked
      periportal nuclear glycogen, and variable portal fibrosis with occasional
      delicate portal-to-portal bridging. Discrete aggregates of distended hepatocytes
      with central nuclei and nonvacuolated clear cytoplasm were present in 5 of the 10
      children, including two 2 OTC deficiency, 2 with CPS deficiency, and 1 with HHH.
      Similar aggregates had been previously noted in the liver of some children with
      OTC deficiency or LPI, but their nature and diagnostic significance had so far
      remained unknown. Using special stains on frozen tissue sections and electron
      microscopy, we show that the hepatocytes in these aggregates have little or no
      cytoplasmic neutral fat, but contain excessive free cytoplasmic glycogen,
      morphologically mimicking a glycogen storage disease. In our experience,
      hepatocellular aggregates of this nature do not occur in Reye syndrome or in any
      of its metabolic mimics other than the subset of defects listed above.
      Identification of these aggregates on liver biopsy can potentially narrow the
      differential diagnosis of a Reye-like syndrome with diffuse hepatocellular
      steatosis.

PMID- 9252148
TI  - Effect of side chain length on biotransformation, hepatic transport, and
      choleretic properties of chenodeoxycholyl homologues in the rodent: studies with
      dinorchenodeoxycholic acid, norchenodeoxycholic acid, and chenodeoxycholic acid.
AB  - To assess the effect of side chain length on the metabolism and physiological
      effects of homologues of chenodeoxycholic acid (CDCA), dinorCDCA, the C22
      homologue, was synthesized and its hepatic biotransformation, transport kinetics,
      and choleretic properties were defined in rat and hamster biliary fistula and in
      isolated perfused rat liver. Results were compared with those of norCDCA, the C23
      homologue, and of CDCA, the natural C24 homologue. In the rat, dinorCDCA was
      secreted mostly in unconjugated form (the majority as dinor-alpha-muricholic
      acid); the remainder was glucuronidated. In the hamster, glucuronidation was
      greater, and the unconjugated fraction contained equal parts of dinorCDCA and
      5beta-hydroxy-dinorCDCA. NorCDCA was glucuronidated extensively (70%, rat; 40%,
      hamster). CDCA, in contrast, was efficiently amidated with taurine or glycine. In
      the perfused liver, the initial uptake rate of all three homologues was
      identical; later, regurgitation and/or cholehepatic shunting of dinorCDCA and
      norCDCA, but not of CDCA, occurred. In rats and hamsters with biliary fistulas,
      dinorCDCA and norCDCA, but not CDCA, induced a bicarbonate-rich hypercholeresis
      of canalicular origin. Hypercholeresis was not induced by the taurine conjugate
      of dinorCDCA. Hepatobiliary retention of both dinorCDCA and norCDCA occurred,
      consistent with efficient ductular absorption (calculated to be 94%) and
      cholehepatic cycling of the unmetabolized bile acids. It is concluded that
      dinorCDCA, as norCDCA, is inefficiently amidated, is metabolized as a xenobiotic,
      and induces hypercholeresis. DinorCDCA is the first dihydroxy bile acid to be
      identified that is secreted largely in unconjugated form in bile.

PMID- 9252149
TI  - Hepatic mitochondrial proliferation in rats with secondary biliary cirrhosis:
      time course and mechanisms.
AB  - It is well known that the hepatic mitochondrial protein content is increased in
      rats 4 weeks after bile duct ligation. In the present study, we measured the time
      course of this increase and assessed the levels of selected mitochondrial
      messenger RNA (mRNA) species and the rate of mitochondrial protein synthesis by
      isolated mitochondria. Three days after surgery, the mitochondrial protein
      content was not significantly different between bile duct-ligated (BDL) and
      control rats, averaging 1,140 +/- 220 mg/liver in BDL and 1,260 +/- 50 mg/liver
      in sham-operated control rats. However, in comparison with control rats, it was
      increased in BDL rats by 35% at 7 days, by 81% at 14 days, and by 27% at 28 days
      after surgery. In vitro mitochondrial protein synthesis, which was assessed as
      the fractional incorporation of [35S]-methionine into mitochondrial protein, was
      not different between BDL and control rats at 3 days after surgery, but was
      decreased in BDL rats by 63% at 7 days, by 55% at 14 days, and by 36% at 28 days
      after surgery. Northern blot analysis revealed an increase in the mRNA levels of
      adenosine triphosphate (ATP)ase subunit 6 and apocytochrome b in BDL rats at day
      7, but no significant differences between BDL and control rats in mitochondrial
      mRNA and ribosomal RNA species 14 and 28 days after surgery. These results show
      that the hepatic mitochondrial protein content rises early after surgery in BDL
      rats, but this rise cannot be ascribed to elevated rates of mitochondrial protein
      synthesis. Thus, increased synthesis of nuclearly encoded mitochondrial proteins
      and/or decreased degradation of mitochondrial proteins appear likely mechanisms
      that lead to the observed increase in the hepatic mitochondrial protein content
      in BDL rats.

PMID- 9252150
TI  - Assessment of hepatic vitamin E status in adult patients with liver disease.
AB  - No published reports compare hepatic alpha-tocopherol (adjusted for hepatic lipid
      content) with indicators of blood alpha-tocopherol in adult patients with various
      liver diseases. alpha-Tocopherol was simultaneously measured in liver biopsy
      tissues and blood from 66 subjects (9 comparison patients hospitalized for
      biliary tract surgery, 13 with chronic persistent hepatitis, 9 with chronic
      aggressive hepatitis, 10 with acute hepatitis, 10 with cirrhosis, 7 with both
      cirrhosis and hepatic cell carcinoma, and 8 with fatty liver). Hepatic,
      erythrocyte, and plasma alpha-tocopherol concentrations were measured, as were
      hepatic and serum lipids. The ratios of alpha-tocopherol to total lipid
      concentrations (Toc/TL ratios) in plasma and liver were calculated. In both
      comparison patients and patients with chronic persistent hepatitis and fatty
      liver, hepatic alpha-tocopherol concentrations were strongly correlated with
      hepatic triglyceride and total lipid concentrations (r = .72, P < .001; and r =
      .75, P < .001, respectively); the relationships (slopes) when hepatic alpha
      tocopherol concentrations were compared with hepatic triglyceride and total lipid
      concentrations were similar in these patients and in all subjects. No strong
      correlations were found between hepatic and blood alpha-tocopherol parameters in
      all subjects. These results suggest that hepatic alpha-tocopherol is present at
      similar concentrations in triglycerides as well as total cholesterol and
      phospholipids and that neither plasma Toc/TL ratios nor erythrocyte alpha
      tocopherol concentrations are useful indicators of hepatic vitamin E status. The
      hepatic Toc/TL ratio may be useful to assess total hepatic vitamin E status.

PMID- 9252151
TI  - Quantitative graphical description of portocentral gradients in hepatic gene
      expression by image analysis.
AB  - The liver consists of numerous repeating, randomly oriented, more or less
      cylindrical units, the lobules. Although enzyme-histochemical or microbiochemical
      assays accurately reflect zonal differences in lobular enzyme content, their
      results cannot be directly compared to biochemical assays. This is because
      section-based assays typically sample along a linear portocentral column of
      cells, even though periportal regions contribute substantially more to hepatic
      volume than pericentral regions. We have developed a time-efficient approach that
      depends on image analysis to determine the prevalence of hepatocytes (pixels)
      with a defined cellular concentration of a particular gene product (absorbance),
      and that generates a graph with the average absorbance per hepatocyte on the
      ordinate and the percentage of hepatocytes with absorbances in each of a
      predetermined range of absorbances incrementally summed on the abscissa. The
      direction of the gradient is read directly from the section. The gradient is a
      graphical representation of the two-dimensional distribution pattern of the gene
      product between the portal tracts and the central veins. The total surface area
      underneath the resulting graph represents the integrated absorbance and is
      equivalent to the outcome of a biochemical assay. The typical linear portocentral
      gradient can be derived from that representing the two-dimensional distribution
      if we assume that liver lobules are uniformly cylindrical or prismatic. The
      analysis, therefore, yields a quantitative description of the relation between
      the enzymatic phenotype of hepatocytes and their position on a normalized
      portocentral radius. We have used the procedure to compare portocentral gradients
      of different enzymes in the same liver and of the same enzyme in different
      livers. In addition, bipolar portocentral gradients of the same enzyme in the
      same liver were analyzed.

PMID- 9252152
TI  - Immunohistochemical studies on endothelial cell phenotype in hepatocellular
      carcinoma.
AB  - To examine the phenotype of the sinusoidal endothelial cells (SECs) surrounding
      tumor cells and the process of capillarization in hepatocellular carcinoma (HCC),
      51 primary HCCs, 4 adrenal metastases, and 3 portal tumor thrombi were
      immunohistochemically stained with monoclonal antibodies (MAbs) for CD4, CD14
      (lipopolysaccharide-binding protein complex receptors), and CD32 (Fc gamma
      receptor II), which are specifically found on the SECs in normal liver, but not
      on ordinary vascular endothelial cells (ECs). Immunostaining was also performed
      for CD36 (thrombospondin receptors), EN4 antigen (Ag) (a pan-vascular endothelial
      cell Ag), PAL-E Ag (a venous and capillary EC Ag), factor VIII-related Ag
      (FVIIIRAg), and laminin. MAb 25F9, which identifies macrophages, was
      simultaneously used with the other MAbs to distinguish macrophages from SECs in
      HCCs (HCC SECs). CD4, CD14, and/or CD32 were found on HCC SECs only in 12 well
      differentiated primary HCCs showing a thin trabecular or pseudoglandular tumor
      cell arrangement. These 12 tumors were smaller than those without CD4-, CD14-,
      and/or CD32-positive SECs (P < .05). Among them, 7, 5, and 11 tumors were
      negative or only partially positive for laminin, PAL-E Ag, and FVIIIRAg,
      respectively. Staining for laminin and PAL-E Ag showed an inverse relationship to
      the expression of CD4, CD14, and CD32 on HCC SECs and the tumor differentiation.
      In conclusion, the phenotypes of the SECs in early and well-differentiated HCC
      are thought to be similar to those of the SECs in normal liver. With progressing
      tumor dedifferentiation the HCC SECs lose the phenotypes peculiar to liver SECs
      and acquire the characteristics of capillary ECs, though both types of
      phenotypical change occur independently of each other.

PMID- 9252153
TI  - Different intrahepatic distribution of phosphatidylglycerol and
      phosphatidylserine liposomes in the rat.
AB  - Liposomes with diameters of 200 to 400 nm containing phosphatidylserine (PS) or
      phosphatidylglycerol (PG) were injected intravenously into rats. Two hours after
      injection, 75% of the injected dose of PS liposomes was found in the liver and
      only 10% found in the spleen, while 35% of the PG liposomes was found in the
      liver and as much as 40% was found in the spleen. Cell-isolation experiments
      revealed the following remarkable difference in the intrahepatic distribution
      between the two liposome formulations: the PS liposomes distributed in about
      equal amounts to Kupffer cells and hepatocytes, despite their size (200-400 nm)
      exceeding that of the endothelial fenestrae (average 150 nm), whereas the PG
      liposomes were only taken up by the Kupffer cells and not at all by the
      hepatocytes. Double-label studies, using liposomes in which the lipid-moiety was
      radio labeled with [3H]cholesteryloleylether ([3H]CE) and the water phase with
      [14C]sucrose, showed that the liposomes were taken up as intact particles. These
      observations were confirmed through electron microscopy by determining the in
      situ localization of liposome-encapsulated colloidal gold particles in thin
      sections of liver and spleen. The differences in organ distribution are ascribed
      to differences in opsonization patterns of the two liposomal surfaces. For the
      difference in intrahepatic distribution, we offer the following two explanations:
      the exploitation of the blood cell-mediated forced sieving concept and the
      indication of a PS-specific pharmacological effect on the dimensions of the
      fenestrations.

PMID- 9252154
TI  - Differential expression of S-adenosylmethionine synthetase isozymes in different
      cell types of rat liver.
AB  - Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, liver
      type and nonhepatic-type enzymes, which are the products of two different genes.
      It is known that the liver-type isozyme is only expressed in adult liver.
      Whereas, the nonhepatic-type isozyme is widely distributed in various tissues. In
      addition to the liver-type isozyme, a minor amount of the nonhepatic-type isozyme
      is also detected in adult liver. To investigate the distribution of these two
      isozymes in the liver in detail, the localization of these two isozymes was
      examined in each cell type of liver using a combination of cell fractionation
      technique and Western blot analysis. In the parenchymal cells, the liver-type
      isozyme protein was predominantly expressed, and a small amount of the nonhepatic
      type isozyme protein was also detected. On the other hand, in the stellate cells
      the nonhepatic-type isozyme protein was exclusively or only expressed.
      Interestingly, a large amount of both isozymes were present in endothelial and
      Kupffer cell fraction. Using both antibodies to anti-rat nonhepatic-type and
      liver-type isozymes, respectively, immunohistochemical analysis clearly confirmed
      these results. In addition, in cultured hepatocellular carcinoma cells (FAA
      HTC1), the nonhepatic-type isozyme protein only was detected, and the liver-type
      isozyme protein completely disappeared. This result indicates that the changes in
      the isozyme expression is regulated within the parenchymal cells. Administration
      of hepatotoxic drug carbon tetrachloride (CCl4) to rats resulted in about 40% to
      50% reduction of enzyme activity in parenchymal cells and stellate cells compared
      with those of control rats. However, enzyme activity in endothelial and Kupffer
      cell fraction was not changed.

PMID- 9252155
TI  - Hepatitis G virus co-infection does not alter the course of recurrent hepatitis C
      virus infection in liver transplantation recipients.
AB  - Although hepatitis G virus infection (HGV) is usually asymptomatic, it has been
      associated with mild hepatic injury. Whether hepatitis G co-infection alters the
      natural history of other viral hepatitis infections remains to be determined. In
      the present study, we investigated whether hepatitis G impacts on the time to
      recurrent hepatitis or on the time to progression to fibrosis in hepatitis C
      infected patients who undergo liver transplantation. Forty-five liver
      transplantation recipients with persistent hepatitis C viremia by polymerase
      chain reaction (PCR) were evaluated. Stored sera obtained before and after liver
      transplantation was tested for HGV RNA by reverse transcriptase (RT)-PCR using
      primers to the 5' region of the HGV genome. A median of eight serial liver biopsy
      specimens were reviewed per patient. The prevalence of HGV co-infection was 21%
      before transplantation and 22% following transplantation. During a median follow
      up of 29 months, 78% (35/45) of patients with hepatitis C viremia developed
      histological features of recurrent hepatitis. Fifty-one percent (23/45)
      progressed to fibrous portal expansion and 16% (7/45) developed bridging
      fibrosis. Comparisons of patients with and without hepatitis G co-infection
      following transplantation showed no significant difference in time to recurrent
      hepatitis, fibrous portal expansion, bridging fibrosis, or of allograft or
      patient survival. In conclusion, hepatitis G co-infection does not seem to impact
      on the time to recurrent hepatitis C or progression of hepatitis C-related
      histological injury after liver transplantation.

PMID- 9252156
TI  - Functional assessment of proliferating hepatocytes stimulated by hepatic
      stimulatory substance in ascorbic acid biosynthetic enzyme-deficient rats.
AB  - The functional ability of hepatic stimulatory substance (HSS)-stimulated
      proliferating hepatocytes was investigated by intrasplenic and/or intraportal
      transplantation in ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od)
      rats that die of osteogenic disorders unless there is AsA supplementation. HSS
      was extracted from regenerating porcine livers. Hepatocytes isolated from the
      livers of congeneic ODS-+/+ rats that are capable of synthesizing AsA were
      transplanted into the spleen (Sp-HTx) and/or the portal vein (Pv-HTx) of ODS
      od/od rats. The recipients were divided into eight groups as follows: HSS
      untreated groups [group Ia, sham-operated, HTx(-); group IIa, Sp-HTx; group IIIa,
      Pv-HTx; and group IVa, Sp- and Pv-HTx], HSS-treated groups [group Ib, HSS only;
      group IIb, Sp-HTx + HSS; group IIIb, Pv-HTx + HSS; and group IVb, Sp- and Pv-HTx
      + HSS]. The recipients were given a diet and water containing AsA for 6 weeks
      after HTx, and AsA supplementation was then halted. The average bromodeoxyuridine
      (BrdU) labeling index (LI) and hepatocyte-occupied ratio in the spleen (H/S
      ratio) of HSS-treated rats were significantly higher than those of HSS-untreated
      rats. All the rats in HSS-untreated groups and group Ib died by 8 weeks after the
      cessation of AsA. In HSS-treated groups IIb, IIIb, and IVb, the survival rates
      were 60%, 50%, and 80%, respectively, at 16 weeks after HTx. The average serum
      AsA level of the surviving rats in groups IIb, IIIb, and IVb was significantly
      higher than that in HSS-untreated groups. These results indicate that HSS
      treatment induced rapid proliferation of transplanted hepatocytes in the spleen
      and the portal vein, and that these proliferating hepatocytes synthesized AsA and
      improved the survival rate of ODS-od/ od rats.

PMID- 9252157
TI  - The prediction of risk of recurrence and time to recurrence of hepatocellular
      carcinoma after orthotopic liver transplantation: a pilot study.
AB  - Orthotopic liver transplantation (OLTx) in the presence of hepatocellular
      carcinoma (HCC) has been complicated by high recurrence rates. The ability to
      determine the risk and timing of HCC recurrence on an individual basis would
      greatly aid in the candidate selection process resulting in a more efficient use
      of donated organs and allow the individualization and better evaluation of
      adjuvant chemotherapy. The 214 patients who underwent OLTx in the presence of HCC
      were analyzed. From the 178 patients who survived more than 150 days, 71 (40%)
      have suffered HCC recurrence. Based on five risk factors, that is, gender, tumor
      number, lobar tumor distribution, tumor size, grade of vascular invasion,
      artificial neural network models predicting the likelihood of HCC recurrence
      within 1, 2, and 3 consecutive years after transplantation were developed. Based
      on model predictions, those combinations of risk factors that should/should not
      lead to recurrence were generated, allowing stratification of patients into the
      following three groups: 1) patients who should not suffer HCC recurrence and who
      should not need adjuvant therapy, 2) patients who will suffer recurrence and for
      whom postoperative chemotherapy significantly prolonged survival (but did not
      prevent recurrence), and 3) patients who may or may not suffer HCC recurrence and
      whose recurrence may be prevented by adjuvant chemotherapy. The outcome of OLTx
      for patients with HCC can be prognosticated based on a number of clinical
      variables. If verified through multicenter trials, these models could be made
      available to transplantation programs performing OLTx in the presence of HCC.

PMID- 9252158
TI  - Hepatic expression of inducible nitric oxide synthase transcripts in chronic
      hepatitis C virus infection: relation to hepatic viral load and liver injury.
AB  - Hepatitis C virus (HCV) causes acute and often also chronic liver disease.
      Hepatocellular injury might result from both a host response directed to inhibit
      viral spread and from processes initiated by the virus itself. To study
      mechanisms involved in hepatocellular injury, liver tissue from chronically HCV
      infected patients was analyzed for the expression of the inducible isoform of
      nitric oxide synthase (iNOS) and for interferon gamma (IFN-gamma) by a
      quantitative, competitive reverse-transcription-polymerase chain reaction (RT
      PCR) technique. Moreover, hepatic viral load was determined by two independent
      techniques, and liver tissue was evaluated histopathologically in detail. Liver
      tissue from HCV-infected patients was shown to express elevated levels of iNOS
      transcripts compared with non-HCV-infected patients. Increased iNOS transcript
      expression, however, was not accompanied by significantly elevated serum nitrite
      plus nitrate (NOx) concentration, although some of the chronic HCV-infected
      patients reached markedly higher serum NOx levels than the control group or
      healthy individuals, respectively. Hepatic iNOS expression was found to be
      positively correlated to hepatic HCV-RNA content on the one hand, and weakly to
      hepatic IFN-gamma expression, previously shown to be solely associated with
      hepatic necro-inflammatory activity among the histopathological parameters
      studied, on the other hand. In contrast to IFN-gamma transcript expression,
      neither hepatic iNOS expression nor hepatic HCV-RNA content were related to
      hepatic inflammatory activity. The presented data are compatible with the
      assumption that HCV might be able to stimulate iNOS expression both directly and
      indirectly via its capacity to induce IFN-gamma.

PMID- 9252159
TI  - Histological findings in chronic hepatitis C with autoimmune features.
AB  - To evaluate the histological findings in patients with chronic hepatitis C and
      autoimmune features, liver tissue specimens from 60 patients were graded under
      code for individual features and composite patterns that denoted autoimmune,
      viral, combined autoimmune and viral, and nondiscriminative changes. Portal,
      interface, and acinar hepatitis in any combination with plasma cell infiltration
      connoted an autoimmune pattern that was associated with higher serum levels of
      gamma-globulin (2.4 +/- 0.2 g/dL vs. 1.7 +/- 0.1 g/dL; P = .0003) and
      immunoglobulin G (2,211 +/- 227 mg/dL vs. 1,508 +/- 83 mg/dL; P = .001) than
      patients with other patterns. Patients with the autoimmune pattern also had a
      greater frequency of cirrhosis (43% vs. 8%; P = .003), higher mean Knodell score
      (13.2 +/- 0.9 vs. 6.8 +/- 0.9; P < .0001), and a greater occurrence of high-titer
      smooth muscle antibodies (SMA) (13% vs. 0%; P = .05) than patients with other
      histological findings. HLA DR3 also occurred more frequently in these individuals
      than in other patients (48% vs. 15%; P = .01) and normal subjects (43% vs. 16%; P
      = .01). Patients with nondiscriminative patterns and interface hepatitis had
      clinical findings similar to those with autoimmune patterns, except for a lower
      mean serum level of gamma-globulin. We conclude that the composite histological
      pattern that resembles autoimmune hepatitis is associated with greater
      immunoreactivity, inflammatory activity, and disease severity than other
      patterns. Interface hepatitis may be the most important histological finding
      associated with these clinical manifestations.

PMID- 9252160
TI  - Enlargement of perihepatic lymph nodes in relation to liver histology and viremia
      in patients with chronic hepatitis C.
AB  - Inflammatory processes in organs frequently lead to hyperplasia of regional lymph
      nodes. In the present study, we investigated whether lymph node enlargement
      within the hepatoduodenal ligament may reflect the inflammatory activity within
      the liver of patients chronically infected with the hepatitis C virus (HCV). In
      114 patients with chronic hepatitis C and 49 healthy controls, the total lymph
      node volume within the hepatoduodenal ligament was prospectively investigated by
      ultrasound. In patients with chronic hepatitis C, a liver biopsy was taken at the
      same occasion, and specimens were semiquantitatively evaluated by the
      histological activity index (HAI). Hepatitis C viremia was assessed by
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). Genotyping
      was performed by a reverse hybridization assay. In 104 of 114 patients (91.2%)
      and in 45 of 49 healthy controls (91.8%), adequate visualization of the region of
      the hepatoduodenal ligament was achieved by ultrasound. Lymph nodes were detected
      in all patients with chronic hepatitis C and in 33 of 45 controls. The mean
      perihepatic lymph node volume in healthy controls (2.2 +/- 1.8 mL) was lower than
      in HCV-infected patients with mild to moderate inflammatory activity, severe
      inflammatory activity, and patients with cirrhosis (5.8 +/- 2.2 mL, 18.1 +/- 10.4
      mL, and 22.8 +/- 18.8 mL, respectively). In patients with HCV-RNA levels of less
      than 10(6) copies/mL, the total lymph node volume was 5.8 +/- 1.6 mL and was
      significantly increased in patients with higher viremia (20.3 +/- 13.8 mL; P <
      10(-6)). No correlation was found between the total lymph node volume within the
      hepatoduodenal ligament, HCV genotypes, and liver function test results. In
      conclusion, enlargement of perihepatic lymph nodes in patients with chronic
      hepatitis C is predictive for the presence of severe inflammatory activity. The
      mechanism of portal lymphadenopathy in patients with chronic hepatitis is unknown
      but appears to be related to viral replication within the liver and the immune
      mediated inflammatory response of the host.

PMID- 9252161
TI  - Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a
      multicenter trial.
AB  - Hepatitis C is a common cause of chronic liver disease that may progress to
      cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of
      ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy
      for an additional 16 weeks. Fifty-nine patients with compensated chronic
      hepatitis C were entered. Efficacy was measured at the end of therapy and after
      follow-up by normalization of alanine aminotransferase (ALT), improvement in
      liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement
      of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT
      values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P <
      .001). No patient maintained a normal ALT when therapy was stopped. No
      significant decrease in level of HCV RNA was observed during the study.
      Histological improvement among subjects who normalized ALT (-1.67 Knodell index)
      was significantly greater than that in other treated patients (+0.33 Knodell
      index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in
      8.3% of placebo recipients whereas no worsening of fatigue was reported by
      ribavirin recipients compared with 16.7% of controls. This difference in fatigue
      was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events
      were generally comparable between treatment groups except for a reversible
      hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in
      four patients on ribavirin. Ribavirin was well tolerated and improved
      aminotransferase values and reduced fatigue in patients with hepatitis C viral
      infection while treatment was being administered. Because this action was
      produced without change in viral level, the mechanism of action of this agent
      requires further investigation.

PMID- 9252162
TI  - A pretransplant infection with precore mutants of hepatitis B virus does not
      influence the outcome of orthotopic liver transplantation in patients on high
      dose anti-hepatitis B virus surface antigen immunoprophylaxis.
AB  - Hepatitis B virus (HBV) infection of the liver graft is a major complication
      after orthotopic liver transplantation (OLT) for HBV-related cirrhosis. A high
      viral load before OLT is a known risk factor, whereas the relevance of precore
      mutants of HBV is a subject of controversy. The aim of this study was to
      correlate the pretransplantation viral load and a pretransplantation infection
      with precore mutant HBV (pmHBV) or wildtype HBV (wtHBV) with allograft damage,
      graft failure, and survival after OLT. Sixty-nine patients with HBV cirrhosis
      underwent OLT under high dose immunoprophylaxis with anti-hepatitis B surface
      (HBs) hyperimmunoglobulins (HBIg). A pretransplantation infection with pmHBV and
      wtHBV was detected by polymerase chain reaction (PCR) and direct sequencing in 30
      patients each (pmHBV and wtHBV group). Nine of 69 patients were PCR-negative
      (noHBV group). Median pretransplantation levels of HBV DNA assessed by
      hybridization assay were 42 pg/mL for pmHBV and 54 pg/mL for wtHBV patients. HBV
      recurred in 17 of 30 (57%) of pmHBV and in 14 of 30 (47%) of wtHBV patients and
      graft failure occurred in 6 of 30 (20%) of pmHBV and 7 of 30 (23%) of wtHBV
      patients. Neither HBV recurrence nor graft failure occurred in patients in whom
      no HBV DNA could be detected by PCR using primers flanking the HBV precore region
      (noHBV) patients. Allograft damage assessed by histology activity index (HAI)
      scoring was median 6 for pmHBV and 7 for wtHBV patients. Cumulative survival
      after 5 years was 72% for pmHBV, 74% for wtHBV, and 100% for noHBV patients. In
      this study, we provide evidence that pretransplantation viral load, but not
      infection with pmHBV, determines the outcome after OLT in patients on high dose
      HBIg prophylaxis.

PMID- 9252163
TI  - Epidemiological factors affecting the severity of hepatitis C virus-related liver
      disease: a French survey of 6,664 patients. The Study Group for the Prevalence
      and the Epidemiology of Hepatitis C Virus.
AB  - Cirrhosis is a frequent and severe event in the course of chronic hepatitis C,
      but it is unclear why some patients develop cirrhosis after a given period
      whereas others do not. We studied a large cohort of patients with chronic
      hepatitis C to determine the role of the route of transmission of hepatitis C
      virus (HCV) in the onset of cirrhosis. Six thousand six hundred sixty-four
      patients were enrolled in a nationwide survey of chronic hepatitis C in France.
      We first randomly defined a representative sample of 30 hospitals with medical
      units managing patients with HCV infection. All patients with chronic hepatitis C
      were enrolled if hepatitis C was diagnosed or treated in these units in 1991,
      1992, or 1993. A questionnaire was filled in from the patients' charts and
      covered demographic data, risk factors for HCV infection, clinical and
      histological data, hepatitis B virus (HBV) and human immunodeficiency virus
      status, and alcohol intake. Descriptive statistics were prepared, and factors
      potentially related to the onset of cirrhosis were identified by means of
      univariate analysis followed by stepwise logistic regression analysis. Among the
      patients enrolled, 21.4% had biopsy-proven cirrhosis. Prevalence of cirrhosis
      markedly varied according to the route of transmission of HCV. It was
      significantly more frequent in blood recipients (23.4%) than in drug users
      (7.0%). Although the occurrence of cirrhosis was dependent on disease duration,
      it remained more frequent in blood recipients than in drug users for a given
      duration. Apart from the route of transmission, excessive alcohol intake was also
      associated with a higher risk of cirrhosis (34.9% vs. 18.2%; P < .001), and so
      was HBV infection (24.6% vs. 21.1%; P < .05). These factors acted independently
      of the route of transmission. Hepatocellular carcinoma was observed in 3.6% of
      all patients and in 17.8% of cirrhotic patients, and its occurrence was strongly
      and mainly related to the presence of cirrhosis. In conclusion, cirrhosis
      occurred in about 20% of the HCV-infected patients in this study and was more
      frequent in blood recipients than in drug users, independently of disease
      duration. Expected changes in the epidemiology of HCV infection might modify the
      risk of developing cirrhosis and, thereafter, cancer.

PMID- 9252164
TI  - Distribution of hepatitis G viremia and antibody response to recombinant proteins
      with special regard to risk factors in 709 patients.
AB  - A new virus named hepatitis G virus (HGV) has been detected recently. Until now,
      no assays for the detection of antibodies against different HGV proteins have
      been commercially available. Therefore, a strip immunoblot assay has been
      established to investigate seroreactivity against recombinant structural (core)
      and nonstructural proteins (NS3 and NS4) of HGV produced in Escherichia coli.
      Seropositivity for HGV was evaluated and concordanced with HGV polymerase chain
      reaction (PCR) results in 709 subjects. These individuals were classified into a
      nonrisk or a risk group, on the basis of infection with human immunodeficiency
      virus (HIV) or hepatitis C virus (HCV) or frequent parenteral exposure, including
      hemophilia, intravenous drug addiction, receipt of blood transfusion, or
      hemodialysis. The nonrisk group consisted of 257 healthy blood donors with normal
      alanine transaminase (ALT) levels (ALT < 30 U/L) and 154 patients with suspected
      non-A-E hepatitis (ALT > 45 U/L). In the group of healthy blood donors, 1.9% (5
      of 257) had detectable HGV viremia and 15.9% (41 of 257) showed antibody response
      to HGV. In the collective of patients with suspected non-A-E hepatitis, results
      from 1.9% of patients (3 of 154) were positive by HGV PCR, and 15.6% of patients
      (24 of 154) showed seropositivity against the recombinant HGV proteins. In six
      groups of patients (n = 298) with different risk factors, the prevalence of both
      HGV viremia (V) and serological reactivity (SR) was higher compared with that of
      the nonrisk group: V, 6.80%-35.2%; serological reactivity (SR), 25.4%-52.9%. The
      following conclusions can be derived from our data. HGV infection is widespread
      in the general population. The prevalence of antibodies against HGV or detectable
      HGV viremia is higher in patients with risk factors for parenteral viral
      transmission than in those without risk factors. The majority of HGV infections
      (70.2%) is self-limiting and not persistent in our collective of patients. We
      found no correlation between HGV viremia and clinical or biochemical signs of
      hepatitis in individuals without risk factors for acquiring parenterally
      transmitted agents.

PMID- 9252165
TI  - Pre-S2 defective hepatitis B virus infection in patients with fulminant
      hepatitis.
AB  - Controversial data were recently published concerning the association of
      hepatitis B virus (HBV) variants with fulminant hepatitis (FH). In this study, we
      first analyzed the complete nucleotide sequences of HBV genomes isolated from
      serum samples from a surgeon and his mother, who was accidentally infected by the
      son; both died of FH. The infecting viruses were genetically almost identical in
      both patients; all the clones examined carried a double nucleotide mutation in
      the start codon of the pre-S2 region that prevented the synthesis of the
      corresponding protein. Analyses of different serum samples from the son revealed
      only wild-type precore sequences in a high viremic serum, whereas hepatitis B e
      antigen (HBeAg)-defective strains were prevalent when the viremia had decreased.
      Subsequently, we extended the analysis to the viral genomes isolated from 18
      additional patients with acute HBV infection and different clinical behaviors: 3
      of 5 patients with FH and without previous liver disease had pre-S2 start codon
      mutations preventing pre-S2 protein synthesis, whereas none of the 13 control
      cases had similar genomic rearrangements. Analysis of the precore region showed
      that viral populations normally producing HBeAg were the only or the prevalent
      viral strains in all of these cases. In summary, our results support the
      hypothesis that the pre-S2 protein is not essential for HBV infectivity. They
      also show that infection by pre-S2-defective virus is frequently associated with
      FH, indicating that this variant might play a pathogenetic role in cases of acute
      liver failure. Finally, they suggest that the emergence of HBeAg-defective
      viruses might be a late event in the course of FH, occurring when HBeAg-producing
      viruses have been mostly cleared.

PMID- 9252166
TI  - Pilot study of the combination of interferon alfa and ribavirin as therapy of
      recurrent hepatitis C after liver transplantation.
AB  - Recurrent hepatitis C virus (HCV) in liver transplant patients is a major cause
      of graft loss, liver failure, and need for retransplantation. The results
      available to date with the use of interferon alfa (IFN-alpha) in the treatment of
      recurrent HCV in liver transplant patients have been disappointing. The aim of
      this study was to evaluate the efficacy and clinical utility of post-transplant
      combination therapy with IFNalpha2b (3 million units 3 times weekly) and oral
      ribavirin (1,200 mg/d) for a duration of 6 months, followed by maintenance with
      ribavirin alone for an additional 6 months. Twenty-one liver transplant
      recipients with recurrent hepatitis C infection (HCV-RNA-positive; active
      hepatitis without rejection on biopsy) were enrolled in this study. Pretreatment
      serum alanine transaminase (ALT) levels were at least two times the upper limit
      of normal. Before treatment, all patients were HCV-RNA-positive and mean HCV-RNA
      titers were 125 million genome-equivalents/mL. Mean pretreatment histological
      score was 6.3 +/- 2. After 6 months of combination therapy, all 21 patients had
      normal ALTs. Ten patients (48%) cleared HCV-RNA from their serum, as assessed by
      polymerase chain reaction (PCR), and HCV-RNA levels decreased significantly in
      the others (P = .0001). Improvement in histological score was seen in all
      patients after combination therapy (P = .0013). During maintenance ribavirin
      monotherapy, ALT remained normal in all but 1 of the 18 patients who tolerated
      therapy. HCV-RNA reappeared in 5 patients, but HCV-RNA levels did not return to
      pretreatment levels (P = .0004). Comparison of pretreatment and postribavirin
      monotherapy liver biopsies revealed improvement in all but 1 of the 18 patients
      who tolerated ribavirin (P = .0002). Side effects were restricted to anemia,
      which necessitated cessation of ribavirin therapy in 3 patients. No patient
      experienced graft rejection during the study period. These results are
      significantly better than those reported with IFN-alpha monotherapy. Most
      importantly, there was a complete absence of graft rejection. These results
      suggest that the combination of IFN-alpha and ribavirin is effective in reducing
      HCV-RNA levels and ameliorating hepatocellular injury in recurrent HCV after
      liver transplantation, and that maintenance therapy with ribavirin monotherapy
      can maintain the biochemical and histological response.

PMID- 9252167
TI  - Ribavirin and interferon for recurrent posttransplantation HCV infection: to
      treat or not to treat?

PMID- 9252168
TI  - Can the prognosis of liver transplantation for hepatocellular carcinoma be
      predicted?

PMID- 9252169
TI  - Is hepatitis C virus a sialodacryoadenitis virus?

PMID- 9252170
TI  - Immortalizing hepatocytes with truncated MET: a little bit of gene goes a long
      way.

PMID- 9252171
TI  - Possible mechanisms for changes of intrasplenic arterial impedance indices in
      portal hypertension.

PMID- 9252172
TI  - Phylogenetic analysis of hepatitis C virus isolates: correlation to viremia,
      liver function tests, and histology.

PMID- 9252173
TI  - Double trouble.

PMID- 9252174
TI  - Backing for anti-cloning bill reopens embryo debate.

PMID- 9252176
TI  - Energy laboratories to open joint DNA sequence 'factory'.

PMID- 9252175
TI  - New DFG head vows to back Germany's young scientists--and genetics research.

PMID- 9252177
TI  - Unesco text will target gene techniques.

PMID- 9252178
TI  - Funds earmarked for AIDS vaccine centre.

PMID- 9252179
TI  - 'First trial' of anti-HIV gene therapy.

PMID- 9252180
TI  - Cloning, dignity and ethical reasoning.

PMID- 9252181
TI  - Alphabetical orders.

PMID- 9252182
TI  - A bug with excess gastric avidity.

PMID- 9252183
TI  - Signal transduction. IkappaB kinase all zipped up.

PMID- 9252184
TI  - Structural biology and phylogenetic estimation.

PMID- 9252186
TI  - A cytokine-responsive IkappaB kinase that activates the transcription factor NF
      kappaB.
AB  - Nuclear transcription factors of the NF-kappaB/Rel family are inhibited by
      IkappaB proteins, which inactivate NF-kappaB by trapping it in the cell
      cytoplasm. Phosphorylation of IkappaBs marks them out for destruction, thereby
      relieving their inhibitory effect on NF-kappaB. A cytokine-activated protein
      kinase complex, IKK (for IkappaB kinase), has now been purified that
      phosphorylates IkappaBs on the sites that trigger their degradation. A component
      of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to
      be the long-sought-after protein kinase that mediates the critical regulatory
      step in NF-kappaB activation.

PMID- 9252185
TI  - The complete genome sequence of the gastric pathogen Helicobacter pylori.
AB  - Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs
      and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori
      has well-developed systems for motility, for scavenging iron, and for DNA
      restriction and modification. Many putative adhesins, lipoproteins and other
      outer membrane proteins were identified, underscoring the potential complexity of
      host-pathogen interaction. Based on the large number of sequence-related genes
      encoding outer membrane proteins and the presence of homopolymeric tracts and
      dinucleotide repeats in coding sequences, H. pylori, like several other mucosal
      pathogens, probably uses recombination and slipped-strand mispairing within
      repeats as mechanisms for antigenic variation and adaptive evolution. Consistent
      with its restricted niche, H. pylori has a few regulatory networks, and a limited
      metabolic repertoire and biosynthetic capacity. Its survival in acid conditions
      depends, in part, on its ability to establish a positive inside-membrane
      potential in low pH.

PMID- 9252187
TI  - A rotating disk of gas and dust around a young counterpart to beta Pictoris.
AB  - beta Pictoris is the best known example of a main-sequence star encircled by a
      tenuous disk. Optical and infrared images of beta Pic suggest that the disk is
      composed of dust grains which have been interpreted as the debris generated by
      the disruption of the asteroid-sized remnants of planet-formation processes. The
      star itself is relatively old, with an age in excess of 100 Myr. Here we present
      high-resolution millimetre-wave images of continuum and molecular-line emission
      from dust and gas surrounding a much younger star, MWC480: the stellar properties
      of MWC480 are similar to those of beta Pic, but its age is just 6Myr. The
      morphology of the circumstellar material and a comparison with the predictions of
      kinematic modelling indicate the presence of a rotating disk, gravitationally
      bound to the star. Moreover, the mass of the disk is greater than the minimum
      required to form a planetary system like our own. We therefore suggest that the
      disk around the young star MWC480 could be a progenitor of debris disks of the
      type associated with older stars such as beta Pic, and so holds much promise for
      the study of both the origin of debris disks and the early stages of the
      formation of planetary systems.

PMID- 9252188
TI  - Dissociating prefrontal and hippocampal function in episodic memory encoding.
AB  - Human lesion data indicate that an intact left hippocampal formation is necessary
      for auditory-verbal memory. By contrast, functional neuroimaging has highlighted
      the role of the left prefrontal cortex but has generally failed to reveal the
      predicted left hippocampal activation. Here we describe an experiment involving
      learning category-exemplar word pairs (such as 'dog...boxer') in which we
      manipulate the novelty of either individual elements or the entire category
      exemplar pairing. We demonstrate both left medial temporal (including
      hippocampal) and left prefrontal activation and show that these activations are
      dissociable with respect to encoding demands. Left prefrontal activation is
      maximal with a change in category-exemplar pairings, whereas medial temporal
      activation is sensitive to the overall degree of novelty. Thus, left prefrontal
      cortex is sensitive to processes required to establish meaningful connections
      between a category and its exemplar, a process maximized when a previously formed
      connection is changed. Conversely, the left medial temporal activation reflects
      processes that register the overall novelty of the presented material. Our
      results provide striking evidence of functionally dissociable roles for the
      prefrontal cortex and hippocampal formation during learning of auditory-verbal
      material.

PMID- 9252189
TI  - Absence of opiate rewarding effects in mice lacking dopamine D2 receptors.
AB  - Dopamine receptors have been implicated in the behavioural response to drugs of
      abuse. These responses are mediated particularly by the mesolimbic dopaminergic
      pathway arising in the ventral tegmental area and projecting to the limbic
      system. The rewarding properties of opiates and the somatic expression of
      morphine abstinence have been related to changes in mesolimbic dopaminergic
      activity that could constitute the neural substrate for opioid addiction. These
      adaptive responses to repeated morphine administration have been investigated in
      mice with a genetic disruption of the dopaminergic D2 receptors. Although the
      behavioural expression of morphine withdrawal was unchanged in these mice, a
      total suppression of morphine rewarding properties was observed in a place
      preference test. This effect is specific to the drug, as mice lacking D2
      receptors behaved the same as wild-type mice when food is used as reward. We
      conclude that the D2 receptor plays a crucial role in the motivational component
      of drug addiction.

PMID- 9252190
TI  - Rab3A is essential for mossy fibre long-term potentiation in the hippocampus.
AB  - Repetitive activation of excitatory synapses in the central nervous system
      results in a long-lasting increase in synaptic transmission called long-term
      potentiation (LTP). It is generally believed that this synaptic plasticity may
      underlie certain forms of learning and memory. LTP at most synapses involves the
      activation of the NMDA (N-methyl-D-aspartate) subtype of glutamate receptor, but
      LTP at hippocampal mossy fibre synapses is independent of NMDA receptors and has
      a component that is induced and expressed presynaptically. It appears to be
      triggered by a rise in presynaptic Ca2+, and requires the activation of protein
      kinase A, which leads to an increased release of glutamate. A great deal is known
      about the biochemical steps involved in the vesicular release of transmitter, but
      none of these steps has been directly implicated in long-term synaptic
      plasticity. Here we show that, although a variety of short-term plasticities are
      normal, LTP at mossy fibre synapses is abolished in mice lacking the synaptic
      vesicle protein Rab3A.

PMID- 9252191
TI  - Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion.
AB  - Rab3 is a neuronal GTP-binding protein that regulates fusion of synaptic vesicles
      and is essential for long-term potentiation of hippocampal mossy fibre synapses.
      More than thirty Rab GTP-binding proteins are known to function in diverse
      membrane transport pathways, although their mechanisms of action are unclear. We
      have now identified a putative Rab3-effector protein called Rim. Rim is composed
      of an amino-terminal zinc-finger motif and carboxy-terminal PDZ and C2 domains.
      It binds only to GTP (but not to GDP)-complexed Rab3, and interacts with no other
      Rab protein tested. There is enrichment of Rab3 and Rim in neurons, where they
      have complementary distributions. Rab3 is found only on synaptic vesicles,
      whereas Rim is localized to presynaptic active zones in conventional synapses,
      and to presynaptic ribbons in ribbon synapses. Transfection of PC12 cells with
      the amino-terminal domains of Rim greatly enhances regulated exocytosis in a Rab3
      dependent manner. We propose that Rim serves as a Rab3-dependent regulator of
      synaptic-vesicle fusion by forming a GTP-dependent complex between synaptic
      plasma membranes and docked synaptic vesicles.

PMID- 9252192
TI  - Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase
      II.
AB  - Repressive chromatin structures need to be unravelled to allow DNA-binding
      proteins access to their target sequences. This de-repression constitutes an
      important point at which transcription and presumably other nuclear processes can
      be regulated. Energy-consuming enzyme complexes that facilitate the interaction
      of transcription factors with chromatin by modifying nucleosome structure are
      involved in this regulation. One such factor, nucleosome-remodelling factor
      (NURF), has been isolated from Drosophila embryo extracts. We have now identified
      a chromatin-accessibility complex (CHRAC) which uses energy to increase the
      general accessibility of DNA in chromatin. However, unlike other known chromatin
      remodelling factors, CHRAC can also function during chromatin assembly: it uses
      ATP to convert irregular chromatin into a regular array of nucleosomes with even
      spacing. CHRAC combines enzymes that modulate nucleosome structure and DNA
      topology. Using mass spectrometry, we identified two of the five CHRAC subunits
      as the ATPase ISWI, which is also part of NURF, and topoisomerase II. The
      presence of ISWI in different contexts suggests that chromatin remodelling
      machines have a modular nature and that ISWI has a central role in different
      chromatin remodelling reactions.

PMID- 9252193
TI  - Activation of paracrine growth factors by heparan sulphate induced by
      glucocorticoid in A549 lung carcinoma cells.
AB  - Alkaline phosphatase, a marker of differentiation in the human alveolar
      adenocarcinoma cell line A549, is inducible by conditioned medium from lung
      fibroblasts and by cytokines including oncostatin M and interleukin 6, but only
      in the presence of a glucocorticoid, dexamethasone. Dexamethasone was shown to
      induce incorporation of [3H]glucosamine into three fractions of medium and cell
      trypsinate from subconfluent A549 cells, eluting from DEAE ion-exchange
      chromatography. The first peak did not correspond to any of the unlabelled
      glycosaminoglycans and was not characterized further. Induction was seen in two
      other peaks, corresponding to hyaluronic acid and heparan sulphate. Of these,
      heparan sulphate, eluting as one well-defined peak (referred to as HS1) and
      another of lower activity and less well defined (HS2), was selected as the most
      likely to interact with growth factors and cytokines and was isolated from the
      eluate, concentrated and desalted, and used in alkaline phosphatase induction
      experiments in place of dexamethasone. HS1 isolated from the medium (HS1m) of
      subconfluent A549 cells was shown to replace dexamethasone in induction
      experiments with fibroblast-conditioned medium, oncostatin M and interleukin 6.
      HS1 from the cell trypsinate and HS2 from the medium and trypsinate were
      inactive. As the activity of HS1m could be abolished by heparinase and
      heparitinase but not by chondroitinase ABC, it was concluded that HS1m was a
      fraction of heparan sulphate involved in the regulation of paracrine growth
      factor activity in lung fibroblast-conditioned medium, and in the regulation of
      other growth factors with potential roles in the paracrine control of cell
      differentiation.

PMID- 9252194
TI  - Immunocytochemical analysis of cisplatin-induced platinum-DNA adducts with double
      fluorescence video microscopy.
AB  - To detect low-level DNA platination, a sensitive immunocyto- and histochemical
      technique was developed using a polyclonal antibody. The antibody GPt, derived
      after immunization of rabbits with highly platinated DNA and purified with
      affinity chromatography, detected the main platinum (Pt)-containing intrastrand
      and interstrand adducts. Double-fluorescence microscopy image analysis was used
      to quantify Pt-DNA adducts with Hoechst 33258 fluorescence to locate the nuclei
      and with fluorescein isothiocyanate fluorescence to measure the immunosignal. A
      two- to five-fold dose-dependent difference in the level of cisplatin (CDDP)
      induced Pt-DNA adducts between a CDDP-sensitive and -resistant human tumour cell
      line was detected. Large differences in Pt-DNA adduct levels after in vitro CDDP
      incubation between human buccal cells, lymphocytes and biopsies of different
      tumour types were observed. Pt-DNA adduct levels were fivefold higher in human
      testicular tumours than in colon tumours, representing CDDP-sensitive and 
      resistant tumours, respectively, in the clinic. These data suggest the
      possibility of predictive testing by measuring Pt-DNA adduct levels. Pt-DNA
      adducts in patients after treatment with CDDP were shown in normal buccal cells
      and in imprints of fresh tumour biopsies as well as in paraffin-embedded tumour
      cells. The analysis of Pt-DNA adducts at a single-cell level in small samples of
      normal and tumour cells during and/or after treatment is feasible with GPt and
      will hopefully enable more selective treatment of patients.

PMID- 9252195
TI  - Nuclear accumulation of p53 correlates significantly with clinical features and
      inversely with the expression of the cyclin-dependent kinase inhibitor
      p21(WAF1/CIP1) in pancreatic cancer.
AB  - Recent studies have suggested a p53-independent expression of p21(WAF1/CIP1). We
      investigated the correlation between p53 overexpression and the expression of
      p21(WAF1/CIP1) in 57 patients with pancreatic adenocarcinoma. By means of reverse
      transcription and polymerase chain reaction (RT-PCR), we examined the mRNA levels
      of WAF1/CIP1 and compared them with the p53 status in 20 patients and in a
      further six pancreatic tumour cell lines. In pancreatic cancer tissues,
      immunohistological evaluation revealed a significant correlation between active
      p53 and p21(WAF1/CIP1) (P < 0.005) as well as WAF1/CIP1 mRNA expression (P <
      0.005). This coherence was also evident in human pancreatic carcinoma cell lines.
      The analysis of p53 and p21(WAF1/CIP1) expression in relation to
      clinicopathological features revealed a significant correlation between p53
      overexpression and tumour stage, tumour size, grading and lymph node metastases,
      whereas p21(WAF1/CIP1) expression correlated only with tumour size. We conclude
      that the expression of p21(WAF1/CIP1) normally depends on active p53, but that
      there may also exist p53-independent pathways of induction that reduce the
      correlation of p21(WAF1/CIP1) to clinicopathological features.

PMID- 9252196
TI  - Time-varying prognostic impact of tumour biological factors urokinase (uPA), PAI
      1 and steroid hormone receptor status in primary breast cancer.
AB  - In breast cancer, several investigations have demonstrated that the tumour
      biological factors uPA urokinase-type plasminogen activator) and its inhibitor
      PAI-1 are statistically independent, strong prognostic factors for disease-free
      (DFS) and overall survival (OS). However, statistical analyses performed for
      varying follow-up periods suggested a time variation of prognostic strength. We
      therefore investigated the time-dependent prognostic power of uPA, PAI-1 and
      steroid hormone receptor status applying the time-varying coefficient model of
      Gray. uPA and PAI-1 were analysed by enzyme-linked immunosorbent assay in tumour
      tissue extracts from 314 breast cancer patients. Hormone receptors (oestrogen and
      progesterone) were determined by radioligand binding or by immunohistochemistry.
      Univariate and multivariate analyses (Cox proportional hazards model) of DFS and
      OS were performed for all patients, including 147 node-negative patients. Median
      follow-up of patients still alive at time of analysis (n = 232) was 58 months.
      Although initially of high prognostic impact, a continuous decrease over time in
      the prognostic power of hormone receptor status and uPA was observed. In
      contrast, the prognostic impact of PAI-1 increased over time and reached similar
      strength as the lymph node status. The time-dependent risk profile of prognostic
      factors may have important clinical implications in regard to follow-up and
      patients' individual risk situation. Evaluation of time dependency of prognostic
      factors may also give a more profound insight into the dynamics of breast cancer
      metastasis.

PMID- 9252197
TI  - Effect of photodynamic therapy in combination with mitomycin C on a mitomycin
      resistant bladder cancer cell line.
AB  - Photodynamic therapy is a method for treating cancer using drugs activated by
      light. A new compound, 5-aminolaevulinic acid (ALA), is a precursor of the active
      photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more
      transient phototoxicity than previous photosensitizers. Cell survival of ALA
      mediated photodynamic therapy was measured in the J82 bladder cancer cell line,
      along with its mitomycin C-resistant counterpart J82/MMC. This demonstrated that
      mitomycin resistance is not cross-resistant to photodynamic therapy. There was
      also a suggestion that the mitomycin-resistant cells were more susceptible to
      photodynamic therapy than the parent cell line. Photodynamic therapy appeared to
      enhance the effect of mitomycin C, when mitomycin C was given first. This
      phenomenon was apparent for both drug-resistant and drug-sensitive cell lines.
      This suggests a possible role for combined mitomycin C and photodynamic therapy
      in superficial bladder tumours that have recurred despite intravesical cytotoxic
      drug treatment.

PMID- 9252198
TI  - Computerized detection of morphological changes to glioma cells during
      estramustine and ion-channel blocker perifusion.
AB  - A perifusion technique for microscopy with computerized detection of early
      changes in cell morphology during continuous perifusion was used to show that the
      geometry of cultured glioma cells (MG-251) changes rapidly when they are exposed
      to estramustine phosphate (EMP). When the cells were exposed to 20 or 40 mg l(-1)
      EMP, cell volume projected cell area (PCA) rapidly increased. When the Na+,K+
      ATPase blocker ouabain (100 micromol l(-1)) was added to the EMP (40 mg l(-1))
      perifusion, the acute EMP response was eradicated. When the PCA curve for ouabain
      alone was subtracted from the curve of combined ouabain and EMP perifusion, the
      resulting curve showed that ouabain completely blocked the EMP-induced increase
      in PCA. When the Na+, K+, Cl- co-transport inhibitors bumetanide (10 micromol l(
      1)), or furosemide (100 micromol l(-1)), were added to EMP (40 mg l(-1)), the
      acute increase in PCA seen for EMP alone was also completely blocked. This study
      shows that inhibitors of ion transmembrane transport can modify EMP-induced cell
      volume increases. This may be of particular importance since the blockers have
      been found to interfere also with the cytotoxic function of EMP during cell
      culture. Thus, it is possible that cell volume changes could serve as a rapid
      technique for predicting the cytotoxic activity of antineoplastic drugs.

PMID- 9252199
TI  - Nitric oxide enhancement of melphalan-induced cytotoxicity.
AB  - The effects of the diatomic radical, nitric oxide (NO), on melphalan-induced
      cytotoxicity in Chinese hamster V79 and human MCF-7 breast cancer cells were
      studied using clonogenic assays. NO delivered by the NO-releasing agent
      (C2H5)2N[N(O)NO]- Na+ (DEA/NO; 1 mM) resulted in enhancement of melphalan
      mediated toxicity in Chinese hamster V79 lung fibroblasts and human breast cancer
      (MCF-7) cells by 3.6- and 4.3-fold, respectively, at the IC50 level.
      Nitrite/nitrate and diethylamine, the ultimate end products of DEA/NO
      decomposition, had little effect on melphalan cytotoxicity, which suggests that
      NO was responsible for the sensitization. Whereas maximal sensitization of
      melphalan cytotoxicity by DEA/NO was observed for simultaneous exposure of DEA/NO
      and melphalan, cells pretreated with DEA/NO were sensitized to melphalan for
      several hours after NO exposure. Reversing the order of treatment also resulted
      in a time-dependent enhancement in melphalan cytotoxicity. To explore possible
      mechanisms of NO enhancement of melphalan cytotoxicity, the effects of DEA/NO on
      three factors that might influence melphalan toxicity were examined, namely NO
      mediated cell cycle perturbations, intracellular glutathione (GSH) levels and
      melphalan uptake. NO pretreatment resulted in a delayed entry into S phase and a
      G2/M block for both V79 and MCF-7 cells; however, cell cycle redistribution for
      V79 cells occurred after the cells returned to a level of cell survival,
      consistent with treatment with melphalan alone. After 15 min exposure of V79
      cells to DEA/NO (1 mM), GSH levels were reduced to 40% of control values;
      however, GSH levels recovered fully after 1 h and were elevated 2 h after DEA/NO
      incubation. In contrast, DEA/NO (1 mM) incubation did not reduce GSH levels
      significantly in MCF-7 cells (approximately 10%). Melphalan uptake was increased
      by 33% after DEA/NO exposure in V79 cells. From these results enhancement of
      melphalan cytotoxicity mediated by NO appears to be complex and may involve
      several pathways, including possibly alteration of the repair of melphalan
      induced lesions. Our observations may give insights for improving tumour kill
      with melphalan using either exogenous or possibly endogenous sources of NO.

PMID- 9252200
TI  - Heterogeneity of DNA content in multiple synchronous hepatocellular carcinomas.
AB  - Heterogeneity of DNA content in multiple hepatocellular carcinomas (HCCs) was
      investigated by flow cytometry in 62 tumours from 26 patients who had undergone
      surgical treatment for multiple synchronous HCCs. Heterogeneity of DNA content
      was defined (a) when tumours had a different DNA ploidy pattern or (b) when the
      difference in the DNA index of the aneuploid clone was more than 0.1. A tumour
      with DNA aneuploidy was observed in 17 (66%) of the 26 patients. Heterogeneity of
      the DNA content was demonstrated in 12 (46%) out of 26 patients: in ten cases by
      definition (a) and in two cases by definition (b). Histological examination
      revealed that, of the 12 patients with a heterogeneous tumour DNA content, seven
      (58%) had a heterogeneous and the remaining five (42%) had a homogeneous type and
      grade of differentiation among the tumours, showing the absence of a relationship
      between histological heterogeneity and DNA content. The present results suggest
      the clinical relevance of DNA content analysis for identifying the clonal origin
      of multiple HCCs.

PMID- 9252201
TI  - Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast
      carcinomas.
AB  - Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by
      immunohistochemical analysis. Immunodetections were assessed using (1) frozen
      sections, (2) documented commercially available monoclonal antibody (bcl-2/124,
      Dako), (3) automation of immunoperoxidase technique (Ventana) and (4)
      quantitative evaluation of results by image analysis (SAMBA) and statistical
      analysis of quantitative data (BMDP software). Bcl-2 protein expression was
      correlated with current prognostic indicators and with molecular markers detected
      by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not
      related to patients' age, tumour size and type or lymph node status, but an
      inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An
      inverse relationship was also observed between Bcl-2 expression and p53 (P <
      0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive
      immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly
      associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2
      positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of
      CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be
      antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is
      strongly detected in low-grade tumours (well-differentiated) with low (MIB1)
      growth fraction, but is independent of the tumour progression (size, node status,
      CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene
      abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved
      in response to endocrine therapy (associated to ER/PR/pS2 positive
      immunoreactions) and probably with chemoresistance mechanisms (inverse
      relationship with P-gp).

PMID- 9252202
TI  - Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in
      nude mice consuming a fish oil diet.
AB  - Lipid peroxidation products can be cytotoxic. Our objectives were (1) to use two
      pro-oxidants (iron and a pro-oxidative drug) to selectively increase lipid
      peroxidation in the implanted human breast tumours of mice consuming fish oil and
      (2) to kill the cancer cells without harming normal host tissues. The theoretical
      basis for selective cytotoxicity is that normal cells are better able to handle
      oxidative stress than cancer cells. Male athymic nude mice, consuming an AIN-76
      diet, were injected s.c. with MDA-MB 231 human breast carcinoma cells. Three
      weeks later, all mice had palpable tumours, 3-10 mm in diameter, and diets were
      changed to modified AIN-76 diets containing 19% menhaden fish oil and 1% corn oil
      with or without supplemental 0.3% ferric citrate. After 2 weeks, half of the mice
      on each diet (19% fish oil with or without supplemental ferric citrate) were
      injected (three times per week for 2 weeks) with the ether-lipid drug edelfosine
      (ET-18-OCH3). The concentration of lipid peroxidation products in tumours (as
      measured by thiobarbituric acid-reactive substances, TBARS) was significantly
      increased by both ferric citrate and ET-18-OCH3. The TBARS in livers were not
      increased, nor was there evidence of other harmful side-effects to the host mice.
      The addition of iron enhanced tumour cell death whereas ET-18-OCH3 suppressed
      tumour cell mitosis. The use of iron supplementation combined with ET-18-OCH3
      resulted in the slowest growth rate, lowest mitotic index, highest level of lipid
      peroxidation products and increased the cytotoxic index in tumours without
      detectable harm to the host. That iron supplementation increased tumour
      suppression beyond that expected from the increase in the concentration of TBARS
      in the tumour merits further investigation.

PMID- 9252203
TI  - Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins
      in mice.
AB  - The biodistribution of two recently developed tumour markers, trimethylated
      (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by
      means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour
      bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after
      administration, the carotenoporphyrin fluorescence was measured in tumoral and
      peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities.
      The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light
      at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD
      camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and
      third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the
      first one is close to the peak of the tissue autofluorescence. The tumour and the
      liver were the two tissue types showing the strongest carotenoporphyrin-related
      fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak
      substance-related fluorescence. In most tissue types, the fluorescence
      intensities decreased over time. A few exceptions were observed, notably the
      liver, in which the intensity remained remarkably constant over the time period
      investigated.

PMID- 9252204
TI  - Polyamine deprivation prevents the development of tumour-induced immune
      suppression.
AB  - Mice grafted with the 3LL (Lewis lung) carcinoma exhibit immune suppression:
      spleen cells showed decreased spontaneous interleukin 2 (IL-2) production and T
      CD4+ and T-CD8+ lymphocyte populations; in addition the polyamine content in the
      spleen was increased. By treating the mice with a polyamine-deficient diet
      containing neomycin, metronidazole and inhibitors of ornithine decarboxylase and
      polyamine oxydase, tumour growth was reduced and the immune abnormalities were
      reversed. The spleen cells overproduced IL-2 by reducing exogenous sources of
      polyamines, but total blockade of all major polyamine sources was necessary to
      obtain an optimal effect both on IL-2 production and on spleen polyamine content.
      Irrespective of whether polyamine deprivation was started at an early or at an
      advanced stage of tumour growth, T-lymphocyte populations were restored to normal
      values, demonstrating that polyamine deprivation not only prevents tumour-induced
      immune suppression, but reverses established immunological disorders. In contrast
      to what was observed regarding IL-2 production by spleen cells and natural killer
      (NK) cell activity, the polyamine oxidase (PAO) inhibitor did not enhance the
      number of T lymphocytes. These findings are consistent with a direct effect of
      the polyamines on immune effector cell metabolism. They suggest an important role
      of the gastrointestinal polyamines and of PAO activity in the regulation of IL-2
      production.

PMID- 9252205
TI  - Ultrasound assessment of residual abnormalities following primary chemotherapy
      for breast cancer.
AB  - The purpose of this study was to assess the usefulness of ultrasonography (US) in
      the assessment of the breast following primary medical therapy (PMT) of large
      operable breast cancer. A total of 52 patients were studied; all had invasive
      breast cancer, confirmed by core biopsy, with initial size > 4 cm by palpation,
      T2-3, N0-1, M0. PMT was with epirubicin, cisplatin and continuous infusional 5
      fluorouracil, as previously described (Jones et al, 1994, J Clin Oncol 12: 1259
      1265). Independent clinical and US assessments were made during PMT before
      surgery or biopsy. A total of 31 (60%) patients achieved complete clinical
      response (cCR), but in only five of these was the post-treatment ultrasound
      normal. Post-treatment sonographic findings of diffuse parenchymal distortion or
      a mass lesion without Doppler signal were associated with more favourable
      histology (pathological CR, non-invasive or microinvasive carcinoma), whereas a
      mass with Doppler positivity was more often associated with residual macroscopic
      invasive carcinoma. Patients who did not achieve cCR had a high incidence of
      residual macroscopic carcinoma (71%) regardless of the sonographic
      characteristics. With median follow-up of 27 months (range 12-43), ten (19%)
      patients have relapsed and six (12%) have died, but only one relapse has occurred
      within treated breast. Ultrasonography is a sensitive technique for assessing the
      response to PMT, particularly in patients who achieve cCR. It may be helpful in
      selecting those patients who do not require post-PMT surgery and in localizing
      abnormalities in those who do, particularly in those with cCR. However,
      clinicians should be aware that a residual US abnormality is by no means
      pathognomonic of residual cancer.

PMID- 9252206
TI  - Sensitivity, specificity and predictive values of breast imaging in the detection
      of cancer.
AB  - In an observational follow-up study we determined whether the combined use of
      mammography and breast ultrasonography is an appropriate diagnostic tool to
      select patients with symptomatic breast disease who need additional pathological
      evaluation. Mammography and ultrasound were used as complementary diagnostic
      modalities in 3014 consecutively referred and mainly symptomatic patients.
      Sensitivity, specificity, predictive values and likelihood ratios were calculated
      according to standard procedures. Virtually complete follow-up was obtained by
      correlating the radiological diagnosis with clinical records, final pathological
      findings, records from the Cancer Register and data from questionnaires sent to
      the general practitioners of all the referred patients. After an average follow
      up period of 30 months, the sensitivity for breast cancer detection was 92.0% and
      the specificity 97.7%. A positive predictive value of 68.0%, a negative
      predictive value of 99.6%, a positive likelihood ratio of 40 and a negative
      likelihood ratio of 0.08 were found. The mean diagnostic delay as a result of
      false negative examinations was 9 months (range 0-20 months). We conclude that
      breast imaging in routine daily practice, consisting of the integral use of
      mammography and ultrasonography, is an appropriate tool in the detection of
      cancer and should be included in the work-up of symptomatic breast disease.

PMID- 9252207
TI  - Elective surgery for colorectal cancer in the aged: a clinical-economical
      evaluation.
AB  - A series of 56 consecutive patients, referred for surgery to a specialized
      institute, had elective laparotomies with various surgical procedures aimed at
      curing locoregional colorectal cancer. Data defining patient and tumour-related
      preoperative, operative and postoperative variables, including costs, were
      collected. The study group was divided into two age groups (< 65 vs > or = 65
      years), which were similar in terms of patient- and tumour-related variables.
      Differences were not statistically significant (Pounds 440; 95% exact CI; Pounds 
      50; 1800). There is no evidence to suggest that there are any total charge
      differences in treating the two age groups, as confirmed by the cost analysis.

PMID- 9252208
TI  - Increased risk of thyroid cancer among Norwegian women married to fishery workers
      -a retrospective cohort study.
AB  - The relationship between thyroid cancer in women and the occupation of their
      spouses was examined in a retrospective cohort study, with special reference to
      fishery. Of the 2.9 million women registered in the Central Population Registry
      of Norway on 31 December 1991, 1.2 million women had a spouse registered with an
      occupation in one or more of the censuses in 1960, 1970 or 1980. The women were
      assigned to ten broad categories based on the first digit of their husbands five
      digit Nordic occupational classification code NYK, and a standardized incidence
      ratio (SIR) was calculated for each occupational category. The women were further
      subdivided and analysed in 71 groups defined by the first two digits of the NYK
      code. Among the women included in the study, a total of 2409 cases of thyroid
      cancer were reported to the cancer registry of Norway during 1960-92. A
      significantly elevated risk of thyroid cancer was found only among women whose
      spouses belonged to the occupational category 'agriculture, forestry or fishery'
      (n = 208 279), with a SIR of 1.13. In the group associated with 'fishing, whaling
      and sealing work' (n = 40 839), the risk was further increased (SIR 1.91, CI 1.65
      2.21). An increased risk was also detected in the group associated with 'ship
      officers and pilots work' (n = 29 133) (SIR 1.35, CI 1.07-1.67). When allocating
      the women to southern and northern cohorts determined by their county of birth, a
      difference in risk was clearly present in all 10 occupational categories, with
      figures being 50-60% higher in the north. However, there was practically no
      difference in incidence between northern and southern cohorts among women
      associated with fishery work. Thus, the results obtained from this study indicate
      that being a fisherman's wife is associated with elevated risk of thyroid cancer,
      and our data support the suggested role of seafood as an aetiological factor.

PMID- 9252209
TI  - Reproducibility and validity of oral visual inspection by trained health workers
      in the detection of oral precancer and cancer.
AB  - A randomized intervention trial is in progress in Kerala, India, to evaluate the
      effectiveness of oral visual inspection by trained health workers (HWs) in the
      prevention of oral cancer. Fourteen health workers with college graduation as the
      basic qualification were trained in oral visual inspection to identify oral
      cancers and precancers among the participants of the screening trial and to refer
      them for further confirmation and management. The aim of the present study was to
      evaluate the reproducibility and validity of the screening test provided by the
      health worker against the reference oral visual findings of three physicians. A
      total of 2069 subjects who had already been examined were re-examined by the
      health workers and physicians. The sensitivity and the specificity of the oral
      visual inspection were 94.3% and 99.3% respectively. There was moderate agreement
      between the findings of the initial and the repeat mouth examinations carried out
      by the health workers, which were on average 6 months apart. There was almost
      perfect agreement (kappa = 0.85) between the findings of the health workers and
      the physicians in identifying the different types of oral precancerous lesions.
      The findings of our study indicate that it is possible to train resource persons
      to perform the oral cancer screening test as accurately as doctors, although
      experience appears to be a crucial component of health workers' accuracy. The
      efficacy of such an approach to reduce the incidence of and mortality from oral
      cancer, however, remains to be proven.

PMID- 9252210
TI  - Lower serum oestrogen concentrations associated with faster intestinal transit.
AB  - Increased fibre intake has been shown to reduce serum oestrogen concentrations.
      We hypothesized that fibre exerts this effect by decreasing the time available
      for reabsorption of oestrogens in the colon. We tested this in volunteers by
      measuring changes in serum oestrogen levels in response to manipulation of
      intestinal transit times with senna and loperamide, then comparing the results
      with changes caused by wheat bran. Forty healthy premenopausal volunteers were
      placed at random into one of three groups. The first group took senna for two
      menstrual cycles then, after a washout period, took wheat bran, again for two
      menstrual cycles. The second group did the reverse. The third group took
      loperamide for two menstrual cycles. At the beginning and end of each
      intervention a 4-day dietary record was kept and whole-gut transit time was
      measured; stools were taken for measurement of pH and beta-glucuronidase activity
      and blood for measurement of oestrone and oestradiol and their non-protein-bound
      fractions and of oestrone sulphate. Senna and loperamide caused the intended
      alterations in intestinal transit, whereas on wheat bran supplements there was a
      trend towards faster transit. Serum oestrone sulphate fell with wheat bran (mean
      intake 19.8 g day(-1)) and with senna; total- and non-protein-bound oestrone fell
      with senna. No significant changes in serum oestrogens were seen with loperamide.
      No significant changes were seen in faecal beta-glucuronidase activity. Stool pH
      changed only with senna, in which case it fell. In conclusion, speeding up
      intestinal transit can lower serum oestrogen concentrations.

PMID- 9252211
TI  - A prospective study of endogenous serum hormone concentrations and breast cancer
      risk in post-menopausal women on the island of Guernsey.
AB  - The associations between serum concentrations of oestradiol, testosterone and sex
      hormone-binding globulin (SHBG) and risk of breast cancer in post-menopausal
      women were investigated in a prospective study on the island of Guernsey. Sixty
      one women who developed breast cancer an average of 7.8 years after blood
      collection were matched for age, year of blood collection and number of years
      post-menopausal with 179 control subjects. Women using exogenous hormones at the
      time of blood collection were excluded from the study. Women who subsequently
      developed breast cancer had a 29% higher geometric mean oestradiol concentration
      than control women (P = 0.004). The odds ratio for breast cancer in the top third
      compared with the lowest third of the oestradiol concentration distribution was
      5.03 (95% confidence interval 2.02-12.49, P for trend < 0.001). Adjusting for
      testosterone and SHBG concentrations did not substantially alter the odds ratio
      for oestradiol. Although testosterone and SHBG concentrations were associated
      with breast cancer risk, the concentrations of these hormones were correlated
      with those of oestradiol; the associations were not statistically significant
      after adjusting for oestradiol concentration. These data provide evidence that
      serum oestradiol concentrations in post-menopausal women may have a substantial
      effect on breast cancer risk.

PMID- 9252213
TI  - Oral contraceptive (OC) use and risk of breast cancer.

PMID- 9252214
TI  - How best to express oestrogen receptor activity.

PMID- 9252212
TI  - Leukaemia and non-Hodgkin's lymphoma in children and young adults: are prenatal
      and neonatal factors important determinants of disease?
AB  - A medical record-based study of leukaemia and non-Hodgkin's lymphoma diagnosed
      before the age of 30 years was carried out at three hospitals in the south of
      England. Findings for 177 cases and 354 age- and sex-matched controls are
      presented here. For documented viral infection in pregnancy, the odds ratio (OR)
      was 6.0 [95% confidence interval (CI) 1.2-29.7] for leukaemia and infinity (95%
      CI 1.24-infinity) for non-Hodgkin's lymphoma. Mothers of leukaemic cases were
      more likely to be anaemic, the OR for a pregnancy haemoglobin below 10 g being
      3.8 (95% CI 1.3-11.1). An association with birthweight was found for acute
      myeloid leukaemia, the OR for birthweights > 3500 g being 6.2 (95% CI 1.3-29.8).
      Further, the preceding siblings of those diagnosed with any form of leukaemia
      were also more likely to weigh > 3500 g at birth (OR 2.2; 95% CI 1.1-4.4).
      Overall, leukaemic cases appeared to be comparatively robust at birth with
      respect to other indicators of well-being, the ORs for jaundice, phototherapy,
      admission to special care nursery and neonatal intensive care all being less than
      1.0. Further, no relation between childhood leukaemia and neonatal administration
      of intramuscular vitamin K was noted (OR 0.6, 95% CI 0.3-1.4; for acute
      lymphoblastic leukaemia diagnosed between the ages of 1 and 6 years).

PMID- 9252215
TI  - De novo protein synthesis in isolated axons of identified neurons.
AB  - Neurons are highly polarized cells that contain a wealth of cytoplasmic and
      membrane proteins required for neurotransmission, synapse formation and various
      forms of neuronal plasticity. Typically, these proteins are differentially
      distributed over somatic, dendritic and axonal compartments. Until recently, it
      was believed that all proteins destined for various neuronal sites were
      synthesized exclusively in the somata and were subsequently targeted to
      appropriate extrasomal compartments. The discovery of various messenger RNA
      molecules in both dendrites and axons is suggestive of de novo protein synthesis
      in extrasomatic regions. The latter process has been demonstrated in few neuronal
      svrstems, but direct proof for the axonal transcription of a specific protein
      from a given messenger RNA is still lacking. This lack of fundamental knowledge
      in the field of cellular and molecular neurobiology is due primarily to both
      anatomical and experimental difficulties encountered in most animal preparations
      studied thus far. In this study we developed a neuronal experimental system
      comprising of individually identified neurons and their isolated axons from the
      mollusc Lymnaea stagnalis. We injected a foreign messenger RNA encoding a peptide
      precursor into the isolated axons of cultured neurons; and utilizing cellular,
      molecular and immunocytochemical techniques, we provide direct evidence for
      specific protein synthesis in isolated axons. The Lymnaea model provides us with
      an opportunity to examine the role and specificity of de novo protein synthesis
      in the extrasomal regions.

PMID- 9252216
TI  - ret receptor tyrosine kinase immunoreactivity is altered in glial cell line
      derived neurotrophic factor-responsive neurons following lesions of the
      nigrostriatal and septohippocampal pathways.
AB  - Glial cell line-derived neurotrophic factor was initially identified as a
      survival factor for developing midbrain dopamine neurons (for reviews, see Refs
      17 and 19). Subsequent studies have demonstrated a more wide-spread role for
      glial cell line-derived neurotrophic factor in the developing and adult CNS. In
      the adult rat brain, for instance, prior administration of glial cell line
      derived neurotrophic factor protects nigrostriatal dopamine neurons from 6
      hydroxydopamine-induced damage. When given several weeks after 6-hydroxydopamine
      injection, glial cell line-derived neurotrophic factor also restores the function
      of these neurons. Glial cell line-derived neurotrophic factor attenuates
      excitotoxin-induced cell death in the striatum and hippocampal formation and
      protective effects of glial cell line-derived neurotrophic factor following
      axotomy have been reported for spinal motor neurons and basal forebrain
      cholinergic neurons. These findings suggest that glial cell line-derived
      neurotrophic factor may be a protective/restorative agent for a diverse
      population of neurons and imply that it may be a useful therapeutic tool for a
      variety of neurodegenerative diseases including Parkinson's, Huntington's and
      Alzheimer's diseases. The potential receptor mediating the pleiotropic effects of
      glial cell line-derived neurotrophic factor has been characterized only recently
      as a novel glycosyl-phosphatidylinositol-linked protein, GDNFR-alpha. Because
      GDNFR-alpha is a cell surface receptor, an additional protein(s) was thought to
      be involved in the glial cell line-derived neurotrophic factor signalling
      cascade. The identity of the likely candidate, ret, was inferred initially from
      indirect evidence. Not only were there remarkable similarities in the
      distribution of glial cell line-derived neurotrophic factor and the proto
      oncogene ret in the developing rat and mouse brain, but also in the phenotype of
      glial cell line-derived neurotrophic factor knockout mice and mice with ret
      mutations. Mice with either mutation exhibited pronounced renal and enteric
      abnormalities, implicating the receptor tyrosine kinase protein product of the
      ret proto-oncogene as the glial cell line-derived neurotrophic factor signalling
      protein. More conclusive evidence showing that activation of GDNFR-alpha by glial
      cell line-derived neurotrophic factor induces phosphorylation of ret has
      confirmed ret as a signalling protein for glial cell line-derived neurotrophic
      factor. Preliminary results showing that 6-hydroxydopamine lesions of the
      substantia nigra markedly reduced ret messenger RNA expression, established its
      localization to presumably glial cell line-derived neurotrophic factor-responsive
      dopamine neurons in the nigrostriatal pathway. In contrast, it is not clear
      whether other glial cell line-derived neurotrophic factor-responsive neurons in
      the CNS, such as the basal forebrain cholinergic neurons and striatal neurons,
      also express ret, nor is it evident whether levels of the protein are regulated
      by disruption of the respective pathways. The present study shows that dense
      networks of ret immunoreactivity are distributed throughout the nigrostriatal
      pathway, with lower densities of staining in other brain regions, including the
      septohippocampal pathway. Following extensive unilateral 6-hydroxydopamine
      lesions of the medial forebrain bundle, ret immunoreactivity in the substantia
      nigra and striatum was reduced significantly, to a similar extent as tyrosine
      hydroxylase immunoreactivity. In contrast, excitotoxic lesions of the striatum,
      achieved by intrastriatal quinolinic acid injections, resulted in increased ret
      staining in this brain region. In addition, marked decrements in septal ret
      immunoreactivity were consequent to complete transections of the fimbria-fornix.

PMID- 9252217
TI  - Social interaction increases the extracellular levels of [Met]enkephalin in the
      nucleus accumbens of control but not of chronic mild stressed rats.
AB  - Chronic application of various mild stress has been shown to decrease the
      responsiveness to reward in rats. This effect, which was suggested to mimic
      anhedonia, one of the main symptoms observed in depressive patients, can be
      measured by various tests. Thus chronic mild stress was shown to reduce the
      consumption of a palatable sucrose solution, and to decrease the acquisition of
      preferences for a distinct environment paired with a variety of reinforcing
      substances. These negative responses could be prevented by chronic treatment with
      tricyclic or atypical antidepressants. The behavioural changes, induced by
      exposure to chronic mild stress, were shown to be associated with a number of
      changes in dopaminergic neurotransmission in the mesolimbic system, especially in
      the nucleus accumbens. The nucleus accumbens contains a large number of
      enkephalinergic cell bodies giving rise to local collaterals and axons projecting
      to the globus pallidus-ventral pallidum region (for review see Ref. 9).
      Furthermore, there is evidence that this structure is instrumental in mediating
      the reward effects of exogenous and endogenous opioids (for reviews see Refs
      5,7,17). This study was carried out to analyse the possible contribution of the
      enkephalinergic system in the anhedonic-like state induced by chronic mild
      stress. Microdialysis was used to study the extracellular levels of
      [Met]enkephalin-like material in the rostral part of the nucleus accumbens of
      freely moving rats exposed or not to chronically mild stress. In both groups, the
      basal levels of [Met]enkephalin-like material were found to be similar. Exposure
      of the two groups to a congener, increased the extracellular levels of
      [Met]enkephalin in the controls but not in chronic mild stressed rats. This
      suggests that the reactivity of the endogenous opioid system could be reduced in
      stress induced model of anhedonia.

PMID- 9252218
TI  - Cell-cell coupling occurs in dorsal medullary neurons after minimizing anatomical
      coupling artifacts.
AB  - Dye (Lucifer Yellow) and tracer (Biocytin) coupling, referred to collectively as
      anatomical coupling, were identified in 20% of the solitary complex neurons
      tested in medullary tissue slices (120-350 microm) prepared from rat, postnatal
      day 1-18, using a modified amphotericin B-perforated patch recording technique.
      Ten per cent of the neurons sampled in nuclei outside the solitary complex were
      anatomically coupled. Fifty-eight per cent of anatomically coupled neurons
      exhibited electrotonic postsynaptic potential-like activity, which had peak-to
      peak amplitudes of < or = 7 mV, with the same polarity as action potentials;
      increased and decreased in frequency during depolarizing and hyperpolarizing
      current injection; was maintained during high Mg2+-low Ca2+ chemical synaptic
      blockade; and was measured only in anatomically coupled neurons. The high
      correlation between anatomical coupling and electrotonic postsynaptic potential
      like activity suggests that Lucifer Yellow, Biocytin and ionic current used the
      same pathways of intercellular communication, which were presumed to be gap
      junctions. Anatomical coupling was attributed solely to the junctional transfer
      of Lucifer Yellow and Biocytin since potential sources of non-junctional staining
      were minimized. Specifically, combining 0.26 mM amphotericin B and 0.15-0.5%
      Lucifer Yellow produced a hydrophobic, viscous solution that did not leak from
      the pressurized pipette tip < or = 3 microm outer diameter) submerged in
      artificial cerebral spinal fluid. Moreover, unintentional contact of the pipette
      tip with adjacent neurons that resulted in accidental staining, another source of
      non-junctional staining, wits averted by continuously visualizing the tip prior
      to tight seal formation with infrared video microscopy, used here for the first
      time with Hoffman modulation contrast optics. During perforated patch recording
      which typically lasted for 1-3 h. Lucifer Yellow was confined to the pipette,
      indicating that the amphotericin B patch was intact. However, once the patch was
      intentionally ruptured at the end of recording, the viscous, lipophilic solution
      entered the neuron resulting in double labeling. Placing a mixture of
      amphotericin B, Biocytin and Lucifer Yellow directly into the pipette tip did not
      compromise tight seal formation with an exposed, cleaned soma, and resulted in
      immediate (<1 min) steady-state perforation at 22-25 degrees C. This adaptation
      of conventional perforated patch recording was termed "rapid perforated patch
      recording". The possible functional implication of cell-cell coupling in the
      dorsal medulla oblongata in central CO2/H+ chemoreception for the
      cardiorespiratory control systems is discussed in the second paper of this set
      [Huang et al. (1997) Neuroscience 80, 41-57].

PMID- 9252219
TI  - Cell-cell coupling between CO2-excited neurons in the dorsal medulla oblongata.
AB  - Anatomically coupled neurons (17 of 137) and non-coupled neurons (120 of 137), in
      and near the nucleus tractus solitarius and dorsal motor nucleus (i.e. solitary
      complex), were studied by rapid perforated patch recording in slices (rat, 150
      350 microm thick, postnatal day 0-21) before, during and after exposure to
      hypercapnic acidosis. Anatomical coupling refers to the intercellular transfer of
      Lucifer Yellow and Biocytin into adjoining neurons, presumably via gap junctions
      [see Dean et al. (1997) Neuroscience 80, 21-40]. Eighty-six per cent of the
      anatomically coupled neurons (12 of 14) were depolarized by hypercapnic acidosis,
      a response referred to as CO2 excitation or CO2 chemosensitivity. In all, 28% (12
      of 43) of the CO2-excited neurons were anatomically coupled to at least one other
      neuron. None (0 of 39) of the CO2-inhibited neurons were anatomically coupled,
      and only 4% (two of 46) of the CO2-insensitive neurons were anatomically coupled.
      Increasing the fractional concentration of CO2 from five to 10 and 15% in
      constant bicarbonate (26 mM) decreased intracellular pH (control 7.3 7.4, 22-25
      degrees C) by approximately 1.0 and 1.5 pH units, respectively, as measured using
      the pH-sensitive fluorescent dye, 2',7'-bis (2-carboxyethyl)-5,6
      carboxyfluorescein. Nine of the anatomically coupled neurons (six CO2-excited,
      one CO2-insensitive and two unidentified) exhibited spontaneous electrotonic
      postsynaptic potential-like activity, suggesting that they were also
      electrotonically coupled. During hypercapnic acidosis, the amplitudes of
      electrotonic postsynaptic potentials were unchanged, concomitant with small
      changes in input resistance. The frequency of electrotonic postsynaptic
      potentials increased during hypercapnic acidosis in many anatomically coupled
      neurons (eight of nine), indicating that both neurons of the coupled pair were
      stimulated. Cell-cell coupling occurred preferentially in and between CO2-excited
      neurons of the solitary complex. Further, CO2-excited neurons were not
      electrotonically uncoupled during intracellular acidosis, in contrast to the
      effect that decreased intracellular pH has on many other types of coupled cells.
      It was not determined whether anatomical coupling was affected by hypercapnic
      acidosis since dye mixture was always administered under normocapnic conditions.
      The high correlation between anatomical coupling, electrotonic coupling activity
      and CO2-induced depolarization suggests that cell-cell coupling is an important
      electroanatomical feature in CO2-excited neurons of the solitary complex. CO2
      excited neurons have been hypothesized to function in central chemoreception for
      the cardiorespiratory control systems, suggesting that cell cell coupling may
      contribute in part to central chemoreception of CO2 and H+.

PMID- 9252220
TI  - Clathrin proteins and recognition memory.
AB  - Strong converging evidence indicates that the intermediate and medial part of the
      hyperstriatum ventrale (IMHV) of the chick forebrain is a site of recognition
      memory for the learning process of imprinting. Clathrin proteins have been
      implicated in synaptic plasticity. In the present study we demonstrate for the
      first time that they are involved in vertebrate learning. Chicks were trained by
      exposure to a conspicuous object and their preference for it versus a novel
      object subsequently measured as a preference score (an index of learning).
      Trained chicks with low preference scores were classed as "poor learners" and
      those with high preference scores as "good learners". An additional group of
      chicks was untrained ("dark-reared"). Tissue was removed from the left and right
      IMHV, hyperstriatum accessorium and posterior neostriatum 9.5 h or 24 h after
      training. Clathrin heavy chain and clathrin light chains a and b were assayed
      using sodium dodecyl sulphate polyacrylamide gel electrophoresis and
      immunoblotting. In the IMHV, and only for clathrin heavy chain, was there a
      significant effect of training. The effect occurred 24 h but not 9.5 h after
      training, and was significant only in the left IMHV. In this region at 24 h,
      there was (i) significantly more clathrin heavy chain in good learners than in
      dark-reared chicks, and (ii) a significant positive correlation between the
      amount of clathrin heavy chain and preference score; the amount of protein
      present in the dark-reared chicks did not differ significantly from the amount
      predicted from the regression line for trained chicks performing at chance
      (preference score 50). These findings imply that for the left IMHV, visual
      experience per se, locomotor activity and other side effects of training did not
      affect the amount of clathrin heavy chain. Rather, the increase observed was a
      function of the amounts chick learned and, because it was delayed, is likely to
      be involved in long-term memory. The results for clathrin heavy chain taken
      together suggest that enhanced presynaptic events in the IMHV, possibly
      associated with an increase in synaptic vesicle release/uptake, are important in
      the recognition memory underlying imprinting.

PMID- 9252221
TI  - Ultrastructural synaptic correlates of spatial learning in rat hippocampus.
AB  - Memory formation is believed to alter neural circuitry at the synaptic level.
      Although the hippocampus is known to play an important role in spatial learning,
      no experimental data exist on the synaptic correlates of this process at the
      ultrastructural level. Here, we have employed quantitative electron microscopy in
      order to compare the density, size and spatial arrangement of synapses in the
      dentate gyrus, and in area CA1, of spatially trained (water maze, invisible
      platform) versus control (visible platform) rats. No training-associated changes
      of hippocampal volume were found using a stereological estimaion (disector) of
      the volume density of dentate granule, or CA1 pyramidal cells. Nor were changes
      found in either density, or sizes of synapses (spinous or dendritic), in CA1 or
      dentate gyrus. However, analysis of synaptic spatial distribution showed a
      training-associated increase in the frequency of shorter distances (i.e.
      clustering) between synaptic active zones in CA1, but not dentate, thus
      indicating alterations in local neural circuitry. This finding indicates subtle
      changes in synaptic organization in area CA1 of the hippocampus following a
      learning experience, suggesting that spatial memory formation in mammalian
      hippocampus may involve topographical changes in local circuitry without synapse
      formation de novo.

PMID- 9252222
TI  - The expression pattern of somatostatin and calretinin by postnatal hippocampal
      interneurons is regulated by activity-dependent and -independent determinants.
AB  - Hippocampal interneurons form distinct populations identified on the basis of
      their projection pattern and neurochemical characteristics, which includes the
      expression of specific neuropeptides and/or calcium-binding proteins. The
      neurochemical maturation of hippocampal interneurons is largely a postnatal
      event, and factors which govern this maturation are presently unknown. Using
      slice cultures, we have investigated the role of neuronal activity in regulating
      the expression of somatostatin and calretinin during the postnatal maturation of
      hippocampal interneurons. Blocking inhibitory activity with bicuculline, or
      excitatory activity with 6,7-dinitroquinoxaline-2,3-dione, for 14 days in slice
      cultures from seven-day-old rat increased and decreased, respectively, the number
      of somatostatin-immunoreactive neurons. Withdrawal of the blocking agents
      resulted in a reversal of the effects on somatostatin immunoreactivity. In
      addition, bicuculline slightly increased the number of calretinin-positive
      neurons, while 6,7-dinitroquinoxaline-2,3-dione exerted no effect. However,
      bicuculline and 6,7-dinitroquinoxaline-2,3-dione markedly increased and
      decreased, respectively, the number of calretinin-labelled axons. Despite
      activity-linked modifications of immunoreactivity levels, no change in the
      organotypic location of somatostatin-labelled neurons was observed, whatever the
      treatment. Double labelling studies demonstrated that somatostatin and calretinin
      were expressed by different neurons, even when the number of labelled cells was
      highly increased. These results show that the levels of expression of
      somatostatin and calretinin in maturing hippocampal interneurons are tuned to the
      endogenous balance of excitatory and inhibitory activity. In contrast, the
      neurochemical specificity of each subtype of interneurons does not depend upon
      variations in neuronal activity.

PMID- 9252223
TI  - Phorbol ester and forskolin suppress the presynaptic inhibitory action of group
      II metabotropic glutamate receptor at rat hippocampal mossy fibre synapse.
AB  - Selective activation of second messenger pathways were tested on presynaptic
      metabotropic glutamate receptor action at mossy fibre-CA3 synapses, using a rat
      hippocampal slice preparation. Application of the protein kinase C activator,
      phorbol 12,13-diacetate, or the adenylate cyclase activator, forskolin, markedly
      enhanced the mossy fibre field excitatory postsynaptic potentials, and suppressed
      the relative magnitude of the synaptic depression induced by (2S,1'R,2'R,3'R)-2
      (2,3-dicarboxycyclopropyl)glycine, an agonist at group-II metabotropic glutamate
      receptors. These effects were also observed in a low Ca2+ solution, suggesting
      that they were not due to saturation of transmitter release process. Inactive
      analogues of the respective activators (4alpha-phorbol 12,13-didecanoate and 1,9
      dideoxyforskolin) neither enhanced the mossy fibre responses nor suppressed
      (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine-induced synaptic depression.
      These results suggest that the presynaptic inhibitory action of group-II
      metabotropic glutamate receptors at mossy fibre-CA3 synapses could be negatively
      regulated by protein kinase C- and cyclic AMP-dependent mechanisms.

PMID- 9252224
TI  - Differential expression of NADPH-diaphorase between electrophysiologically
      defined classes of pyramidal neurons in rat ventral subiculum, in vitro.
AB  - The subiculum is the major output region of the hippocampal formation. We have
      studied pyramidal neurons in slices of rat ventral subiculum to determine if
      there is a correlation between nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) activity and electrophysiological phenotype. The majority of
      NADPH-d-positive pyramidal neurons were found in the superficial cell layer (i.e.
      nearest to the hippocampal fissure) of the subiculum and appreciable NADPH-d
      activity was absent from pyramidal neurons in area CA1. This distribution of
      NADPH-d activity was mimicked by that of immunoreactivity for the neuronal
      isoform of nitric oxide synthase. Subicular pyramidal neurons were classified,
      electrophysiologically, as intrinsically burst-firing or regular spiking. After
      electrophysiological characterization, neurons were filled with Neurobiotin and
      revealed using fluorescence immunocytochemistry. The slices containing these
      neurons were also processed for NADPH-d. NADPH-d activity was found in six out of
      eight regular spiking neurons but was not found in any of 13 intrinsically burst
      firing neurons (P=0.0008, Fisher's Exact Test). We conclude that in rat ventral
      subiculum, NADPH-d activity is present in a proportion of pyramidal neurons and
      indicates the presence of the neuronal isoform of nitric oxide synthase.
      Furthermore, amongst pyramidal neurons, NADPH-d activity is distributed
      preferentially to those with the regular spiking phenotype. The distribution of
      regular spiking neurons suggests that they may not be present to the same extent
      in all subicular output pathways. Thus, the actions of nitric oxide may be
      relatively specific to particular hippocampal connections.

PMID- 9252225
TI  - Comparison of NADPH diaphorase histochemistry, somatostatin immunohistochemistry,
      and silver impregnation in detecting structural and functional impairment in
      experimental status epilepticus.
AB  - Nitric oxide has been postulated as a retrograde intercellular messenger for long
      term potentiation, a form of synaptic plasticity that is associated with learning
      and memory processes. In the present study we investigated whether the loss or
      survival of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase
      containing neurons, which are known to synthesize nitric oxide, would be an
      useful indicator for evaluating the structural and functional state of the rat
      hippocampus after status epilepticus that is induced by intraperitoneal injection
      of kainic acid. Besides NADPH diaphorase histochemistry, two other histological
      parameters were studied: the grade of cell damage evaluated from silver
      impregnated sections, and the number of somatostatin-containing neurons in
      different hippocampal subfields. We found that the number of NADPH diaphorase
      containing neurons in the hilus and granule cell layer correlated well with
      spatial learning and memory performance as assessed by the Morris water-maze
      test. The extent of cell damage in the CA1 subfield analysed in silver
      impregnated sections and the number of hilar somatostatin-containing neurons also
      significantly correlated with latencies in the water-maze test. Furthermore,
      linear regression analysis revealed that the number of somatostatin-containing
      neurons in the hilus explains about 50% of the variation in water-maze learning.
      These findings emphasize that although general structural preservation is of
      crucial importance for the function of the hippocampus also interneurons, such as
      somatostatin- and NADPH diaphorase-containing neurons, may play an important role
      during the acquisition phase and processing of information in hippocampal
      circuitry. Therefore, in addition to evaluating general cell damage, analysis of
      the cell loss that occurs in the interneuron subpopulations will be beneficial in
      verifying structural and functional deficits of the hippocampus after status
      epilepticus.

PMID- 9252226
TI  - Prolonged inhibitory potentials in layer III projection cells of the rat medial
      entorhinal cortex induced by synaptic stimulation in vitro.
AB  - The entorhinal cortex projects via layer III neurons directly to the hippocampal
      area CA1 and the subiculum. We studied the functional properties of the medial
      entorhinal cortex projection cells in horizontal hippocampal-entorhinal cortex
      combined slices. These cells displayed, upon single-shock synaptic stimulation,
      an excitatory postsynaptic potential followed by a fast and/or slow inhibitory
      postsynaptic potential. Short train repetitive stimulation subthreshold for
      generation of action potentials induced a slow hyperpolarization of up to 20 s.
      Pharmacological analysis shows that the slow hyperpolarization could be divided
      into three components: i) the first component, which lasted 1 s, was sensitive to
      GABA(B) receptor antagonists; ii) the second component lasting for about 6 s was
      sensitive to atropine, suggesting muscarinic acetylcholinergic nature of these
      responses; iii) a late component lasting for up to 20 s was sensitive to
      naloxone, suggesting a role for opioids in its generation. The finding that layer
      III projection neurons to the hippocampus proper develop long-lasting
      hyperpolarizations suggests possible control mechanisms for the output functions
      of the entorhinal cortex.

PMID- 9252227
TI  - Morphofunctional evidence for mature synaptic contacts on the Mauthner cell of 52
      hour-old zebrafish larvae.
AB  - In a previous study, miniature inhibitory synaptic events recorded in the
      Mauthner cell of the 52-hour-old zebrafish larvae (Brachydanio rerio) were found
      to be mainly glycinergic. Their amplitude distribution was not Gaussian and it
      was proposed that their large amplitude variation might reflect the activation of
      immature synapses. However, ultrastructural studies of the synaptic contacts over
      the M-cell soma of 52 h larvae described here, revealed that numerous synaptic
      contacts on this neuron are already mature at this developmental stage and that
      most of them already contain a single active zone. As in the adult goldfish,
      immunohistochemistry indicates the presence of both glycine- and GABA
      immunoreactive boutons which establish synaptic contacts. We also found that, in
      addition to the predominant glycinergic postsynaptic inhibitory currents, some
      postsynaptic currents are also GABAergic since they are specifically inhibited by
      bicuculline (20 microM). GABAergic miniature events (time to peak close to 0.8 ms
      and decay time-constant close to 45 ms) were only detected in the presence of
      11.5 mM [KCl]o. Their amplitude distributions were well fitted by one, or at most
      two, Gaussian curves. Outside-out recordings showed one class of GABA receptors
      with a main conductance state of 23 pS. This indicates that the smallest
      GABAergic miniature inhibitory synaptic events correspond to the opening of 14-20
      chloride channels Pre- and postsynaptic factors which contribute to the
      predominance of glycinergic synaptic currents over GABAergic ones in untreated
      preparations and to the striking differences between their frequencies and their
      respective amplitude distribution histograms are discussed with reference to the
      morphological characteristics of the mature synaptic endings impinging on this
      still developing neuron.

PMID- 9252228
TI  - Localization of the messenger RNA for the c-Jun NH2-terminal kinase kinase in the
      adult and developing rat brain: an in situ hybridization study.
AB  - Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c
      Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates
      and activates stress-activated protein kinase/c-Jun NH2-terminal kinase, a
      recently discovered mitogen-activated protein kinase that is stimulated by
      stressful stimuli and that regulates cellular transcriptional activity. The
      distribution of the messenger RNA encoding for stress-activated protein
      kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult
      and developing rat central nervous system. In situ hybridization with a 35S
      labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the
      stress-activated protein kinase/extracellular signal-regulated protein kinase-1
      messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains.
      Specific labelling was generally associated with neuronal profiles. In the adult
      central nervous system, high hybridization signals were observed in the
      hippocampus, the granular layer of the cerebellum, the medial habenula, the
      anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial
      nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the
      hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus.
      Intermediate levels were present in diencephalic and mesencephalic regions and in
      the neocortex, while basal ganglia displayed a low hybridization signal. In the
      developing brain, the heterogeneous distribution of the hybridization signal
      observed in the adult brain was already present, but in the hippocampus and basal
      ganglia the stress-activated protein kinase/extracellular signal-regulated
      protein kinase-1 messenger RNA levels were significantly higher at postnatal day
      3 and during the second postnatal week than in the adult. The results show that
      stress-activated protein kinase/extracellular signal-regulated protein kinase-1
      is widely expressed in the rat central nervous system and co-localizes with its
      substrate stress-activated protein kinase. The observed changes in stress
      activated protein kinase/extracellular signal-regulated protein kinase-1
      messenger RNA levels during postnatal development suggest a role for this protein
      in the maturation of brain circuits.

PMID- 9252229
TI  - The expression of voltage-dependent calcium channel beta subunits in human
      cerebellum.
AB  - The beta subunits of voltage-dependent calcium channels, exert marked regulatory
      effects on the biophysical and pharmacological properties of this diverse group
      of ion channels. However, little is known about the comparative neuronal
      expression of the four classes of beta genes in the CNS. In the current
      investigation we have closely mapped the distribution of beta1, beta2, beta3 and
      beta4 subunits in the human cerebellum by both in situ messenger RNA
      hybridization and protein immunohistochemistry. To our knowledge, these studies
      represent the first experiments in any species in which the detailed localization
      of each beta protein has been comparatively mapped in a neuroanatomically-based
      investigation. The data indicate that all four classes of beta subunits are found
      in the cerebellum and suggest that in certain neuronal populations they may each
      be expressed within the same cell. Novel immunohistochemical results further
      exemplify that the beta voltage-dependent calcium channel subunits are regionally
      distributed in a highly specific manner and studies of Purkinje cells indicate
      that this may occur at the subcellular level. Preliminary indication of the
      subunit composition of certain native voltage-dependent calcium channels is
      suggested by the observation that the distribution of the beta3 subunit in the
      cerebellar cortex is identical to that of alpha(1E). Our cumulative data are
      consistent with the emerging view that different native alpha1/beta subunit
      associations occur in the CNS.

PMID- 9252230
TI  - Abnormalities in the cerebellum and brainstem in homozygous lurcher mice.
AB  - The lurcher mutation induces Purkinje cell degeneration in heterozygous mice, and
      neonatal death in homozygous animals. Using the D6Mit16 Simple Sequence Length
      Polymorphic marker in F2 hybrids between AKR +/+ mice and B6+/Lc mice, homozygous
      lurcher fetuses and newborns as well as heterozygous and normal littermates were
      identified, and their brain morphology was analysed. In homozygous lurcher
      embryos at embryonic day 18 and neonates the cerebellum was hypotrophic,
      particularly in the posterior half. Purkinje cells were smaller in the whole
      cerebellum and showed a maturational delay. Calretinin-positive cells were less
      frequently observed in the depth of the vermis than in normal mice. Both Purkinje
      cells and the vermal calretinin-positive cells were more abnormal in fetuses at
      day 19 and newborn mutants than one day earlier. An abnormal number of pycnotic
      cells were observed in the cerebellum, especially in newborn mutants. Brainstem
      abnormalities were characterized by abnormal curvature, caudal displacement of
      the pontine gray nuclei which were located caudally along the ventral border of
      the superior olivary complex, a drastic decrease in Purkinje cell axons in all
      the vestibular nuclei and the presence of dystrophic processes in at least two
      calbindin-positive cell groups of the dorsal pontine region. These results show
      that the mutation, which is semidominant in Purkinje cells, is recessive in other
      cell groups of the cerebellum and brainstem. They reveal that the sequence
      leading to Purkinje cell death appears to be similar in homozygous and
      heterozygous mice, although occurring earlier and worsening more quickly in the
      former. Lastly, they confirm the absence of effect of the mutation on the neurons
      of the inferior olivary complex.

PMID- 9252231
TI  - Nicotinic receptor-mediated responses in relay cells and interneurons in the rat
      lateral geniculate nucleus.
AB  - We used the in vitro whole-cell recording technique to study the nicotinic
      responses of relay cells and interneurons in the adult rat dorsal lateral
      geniculate nucleus, the thalamic nucleus that conveys visual signals from the
      retina to the cortex. These geniculate relay cells and interneurons were
      identified by their physiological and morphological properties. We found that, in
      the presence of a muscarinic antagonist, atropine, acetylcholine induced a
      depolarization in relay cells. A similar depolarization was induced by
      application of nicotine. These depolarizations were completely blocked by a
      nicotinic antagonist, hexamethonium, but were little affected by bath solution
      that contained tetrodotoxin and/or low calcium concentration to block synaptic
      transmission. This suggests that the depolarization is mediated directly by
      nicotinic receptors in relay cells. Application of nicotine also induced a
      depolarization in geniculate interneurons. The interneurons continued to exhibit
      a response to nicotine in the presence of synaptic blockade, although the time
      course of the response was altered. The nicotinic responses in relay cells and
      interneurons shared many similar properties. Both exhibited desensitization,
      although this characteristic was much more pronounced in the interneurons. In
      both cell types, the nicotinic response activated a relatively linear conductance
      with a slight inward rectification. The reversal potential for the conductance
      was about - 33 mV, which is consistent with a permeability to sodium and
      potassium ions. The reversal potential shifted negatively by 5-6 mV when the bath
      solution contained low calcium, which further suggests a permeability to calcium
      ions. Our results indicate that nicotinic receptors are present in both
      geniculate relay cells and interneurons. The nicotinic depolarization in relay
      cells may serve to enhance transmission of visual signals through the lateral
      geniculate nucleus as well as to contribute to a voltage-dependent shift in the
      response mode of geniculate relay cells from burst to tonic (single-spike)
      firing. The nicotinic depolarization in interneurons may provide an explanation
      for reports that activation of the cholinergic system can enhance inhibitory
      tuning in the lateral geniculate nucleus.

PMID- 9252232
TI  - Optical characterization of a novel GABA response in early embryonic chick
      brainstem.
AB  - To examine the functional expression of embryonic GABA receptors, the inhibitory
      effects were studied of GABA (GABA responses) on the excitatory postsynaptic
      potentials evoked by vagal stimulus in seven- to 10-day-old embryonic chick
      brainstem slice preparations. A multiple-site optical recording technique was
      used, with a multiple element photodiode array system and a fast voltage
      sensitive merocyanine-rhodanine dye (NK2761). First, in the GABA response, three
      components were pharmacologically identified: component 1, related to GABA(A)
      receptors; component 2, related to GABA(B) receptors; and component 3 which is
      insensitive to GABA(A) and GABA(B) antagonists, but is stimulated by both GABA(A)
      and GABA(B) agonists. Subsequently. the embryogenesis and early development of
      the three components were investigated, and early developmental maps of regional
      distribution patterns of the three components were constructed. Components 1 and
      3 have already emerged in the seven-day-old embryonic brainstem preparation;
      component 2 appeared in the eight-day-old preparations. No component related to
      GABA(C) receptors was observed in the seven- to 10-day-old embryonic stages. From
      the pharmacological properties of component 3, we suggest that it is related to a
      new subtype, the GABA(D) receptor.

PMID- 9252233
TI  - Differential cellular distribution and dynamics of HSP70, cyclooxygenase-2, and c
      Fos in the rat brain after transient focal ischemia or kainic acid.
AB  - Cerebral ischemia and also excitotoxicity induce the expression of 72,000 mol. wt
      heat shock protein (Hsp70), c-Fos, and cyclooxygenase-2. In the present work we
      have examined whether Hsp70, c-Fos and cyclooxygenase-2 are expressed by the same
      cells in the rat brain at 6, 12 and 24 h following transient focal ischemia or
      kainic acid administration, by means of single and double immunohistochemistry.
      At 6 h after kainic acid, some co-localization of Hsp70 with c-Fos and
      cyclooxygenase-2 was seen in pyramidal hippocampal neurons and superficial
      cortical layers, however by 24 h such colocalization became rare within the
      cortex but was partially maintained in the hippocampus. Cyclooxygenase-2 was seen
      in many neurons that were also immunoreactive for c-Fos in superficial cortical
      layers, dentate gyrus and pyramidal cell layer of the hippocampus from 6 h after
      kainic acid. Co-localization of cyclooxygenase-2 and c-Fos was also observed in
      superficial cortical layers within the ipsilateral hemisphere at 6 h following
      focal ischemia. Also, some co-localization of Hsp70 with c-Fos and cyclooxygenase
      2 was seen at this time. However, by 24 h cyclooxygenase-2 and c-Fos
      immunoreactive cells were restricted to perifocal regions, and only a very
      limited co-localization with Hsp70 was seen in perifocal neurons located in the
      border of the penumbra-like area that surrounds the ischemic core and is strongly
      immunoreactive for Hsp70. This study shows a selective and dynamic cellular
      expression of inducible proteins following either ischemia or kainic acid, with a
      remarkable neuronal co-localization of c-Fos and cyclooxygenase-2. The results
      suggest that, first, stimuli underlying neuronal c-Fos expression can also lead
      to the induction of cyclooxygenase-2; second, transient co-localization of Hsp70
      and c-Fos can take place in non-vulnerable neurons; and finally, expression of c
      Fos, cyclooxygenase-2, and/or Hsp70 at a given time-point is part of the response
      to altered environmental conditions and can be related to the particular cellular
      sensitivity rather than the pathological outcome.

PMID- 9252234
TI  - A microdialysis study on pineal melatonin rhythms in rats after an 8-h phase
      advance: new characteristics of the underlying pacemaker.
AB  - This study describes the use of the microdialysis technique to elucidate specific
      properties of the circadian pacemaking system in the hypothalamus, by measurement
      of melatonin production in the pineal gland. Melatonin has appeared to be a
      reliable marker of the pacemaker activity, which is influenced by the light/dark
      cycle. A phase shift in the light/dark cycle was applied to perturb the rhythm
      generating system. An 8-h phase advance resulted in the disappearance of
      melatonin production over two days, with basal levels comparable to normal
      daytime levels. In the subsequent return of rhythmic melatonin production, new
      clock characteristics could be revealed, due to the high time-resolution
      measurements of microdialysis. While half of the animals still did not show any
      rhythmicity, the other half of the animals regained rhythmicity with entrained
      onset of melatonin production, while the offset was variable and not stably
      entrained to lights on. Ten days after the shift, the system had completely
      recovered and all animals regained normal rhythmicity, in phase with the new
      light/dark cycle. The results are interpreted in terms of the two-oscillator
      model, with one oscillator reacting with a phase advance and the other with a
      phase delay to adapt to the phase shift.

PMID- 9252235
TI  - Histamine H3 receptor activation selectively inhibits dopamine D1 receptor
      dependent [3H]GABA release from depolarization-stimulated slices of rat
      substantia nigra pars reticulata.
AB  - The release of [3H]GABA from slices of rat substantia nigra pars reticulata
      induced by increasing extracellular K+ from 6 to 15 mM in the presence of 10
      microM sulpiride was inhibited by 73 +/- 3% by 1 microM SCH 23390, consistent
      with a large component of release dependent upon D1 receptor activation. The
      histamine H3 receptor-selective agonist immepip (1 microM) and the non-selective
      agonist histamine (100 microM) inhibited [3H]GABA release by 78 +/- 2 and 80 +/-
      2%, respectively. The inhibition by both agonists was reversed by the H3 receptor
      antagonist thioperamide (1 microM). However, in the presence of 1 microM SCH
      23390 depolarization-induced release of [3H]GABA was not significantly decreased
      by 1 microM immepip. In rats depleted of dopamine by pretreatment with reserpine,
      immepip no longer inhibited control release of [3H]GABA, but in the presence of 1
      microM SKF 38393, which produced a 7 +/- 1-fold stimulation of release, immepip
      reduced the release to a level not statistically different from that in the
      presence of immepip alone. Immepip (1 microM) also inhibited the depolarization
      induced release of [3H]dopamine from substantia nigra pars reticulata slices, by
      38 +/- 3%. The evidence is consistent with the proposition that activation of
      histamine H3 receptors leads to the selective inhibition of the component of
      depolarization-induced [3H]GABA release in substantia nigra pars reticulata
      slices which is dependent upon D1 receptor activation. This appears to be largely
      an action at the terminals of the striatonigral GABA projection neurons, which
      may be enhanced by a partial inhibition of dendritic [3H]dopamine release.

PMID- 9252236
TI  - Stimulus intensity, cell excitation and the N-methyl-D-aspartate receptor
      component of sensory responses in the rat spinal cord in vivo.
AB  - The importance of receptors for N-methyl-D-aspartate in synaptic plasticity and
      in triggering long-term pronociceptive changes is explained by their voltage
      dependence. This suggests that their contribution to acute nociceptive responses
      would be determined both by the magnitude of synaptic input and by the level of
      background excitation. We have now examined the role of N-methyl-D-aspartate
      receptors in acute nociceptive transmission in the spinal cord. Drugs selectively
      affecting activity mediated by these receptors were tested on responses of dorsal
      horn neurons to noxious stimuli of different intensities and at different levels
      of ongoing spike discharge. The drugs used were the N-methyl-D-aspartate receptor
      channel blocker ketamine; the competitive antagonists, 3-((R)-2-carboxypiperazin
      4-yl)-propyl-1-phosphonic acid (D-CPP) and D-2-amino-5-phosphonopentanoic acid (D
      AP5), and the positive modulator thyrotropin-releasing hormone. The activity of
      dorsal horn wide dynamic range neurons was recorded extracellularly in alpha
      chloralose-anaesthetized spinalized rats. Their responses to noxious stimuli
      (pinch, heat and electrical) were monitored in parallel with responses to
      iontophoretic N-methyl-D-aspartate and (RS)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-propionic acid (AMPA). Drugs were given i.v. or (D-AP5)
      iontophoretically. At doses that selectively inhibited responses to exogenous N
      methyl-D-aspartate, ketamine (4 or 8, mean 5 mg/kg i.v.) reduced the nociceptive
      responses of the majority of the cells in deep dorsal horn. Ketamine also reduced
      wind-up of the responses to repetitive electrical stimulation. Ketamine (4 or 8
      mg/kg). D-CPP (2 mg/kg), D-AP5 (iontophoretically) and thyrotrophin-releasing
      hormone (1 mg/kg) were tested on different magnitude nociceptive responses evoked
      by alternating intensities of noxious heat or pinch. In percentage terms, the
      less vigorous responses were affected by all four drugs as much as or more than
      the more vigorous responses. When background activity of neurones was enhanced by
      continuous activation of C-fibres with cutaneous application of mustard oil,
      ketamine was less effective against superimposed noxious pinch responses. Ongoing
      background activity was affected in parallel with evoked responses. When
      background discharge of the cells was maintained at a stable level with
      continuous ejection of kainate, neither the N-methyl-D-aspartate antagonists nor
      thyrotrophin-relasing hormone affected the responses to noxious pinch or heat,
      although responses to exogenous N-methyl-D-aspartate were still blocked. The wind
      up of the electrical responses was, however, reduced by ketamine irrespective of
      the level of background activity. The results indicate that under these
      conditions in vivo, N-methyl-D-aspartate receptors mediate ongoing low-frequency
      background activity rather than phasic high-frequency nociceptive responses. The
      effects of N-methyl-D-aspartate antagonists and positive modulators on
      nociceptive responses are evidently indirect, being secondary to changes in
      background synaptic excitation. These results cannot be explained simply in
      relation to the voltage-dependence of N-methyl-D-aspartate receptor-mediated
      activity; other factors, such as modulation by neuropeptides, must be involved.

PMID- 9252237
TI  - Toxin-resistant calcium currents in embryonic mouse sensory neurons.
AB  - We characterized toxin-insensitive calcium currents expressed by acutely
      dissociated embryonic dorsal root ganglion neurons. In the presence of 3 microM
      omega-conotoxin-GVIA, 3 microM nitrendipine and either 500 nM omega-agatoxin-IVA
      or 500 nM omega-conotoxin-MVIIC to inhibit N-, L- and P/Q-type currents,
      respectively, all neurons expressed two residual currents: a T-type and another
      which we referred to as toxin-resistant current. The toxin-resistant current (i)
      consisted of an inactivating and a sustained components, (ii) had a threshold of
      activation and a steady-state inactivation comprised between that of the T-type
      current and that of the other high-voltage-activated currents, (iii) had the same
      permeability for barium and calcium used as charge carriers, (iv) was highly
      sensitive to both cadmium and nickel; and (v) was insensitive to 500 microM
      amiloride which abolished the T-type at this concentration. The properties of the
      toxin-resistant current are very similar to those of the currents expressed in
      oocytes following injection of alpha(1E) subunits which we demonstrated to be
      present in these neurons. Therefore a component of the toxin-resistant current
      calcium channels in sensory neurons may be closely related to those calcium
      channels formed by alpha(1E) subunits.

PMID- 9252238
TI  - Role of hypothalamic neuropeptide Y neurons in the defective thermogenic response
      to acute cold exposure in fatty Zucker rats.
AB  - The fatty Zucker rat has impaired heat production and fails to mount an adequate
      thermogenic response to cold exposure, partly because of decreased sympathetic
      drive to thermogenesis in brown adipose tissue. Neuropeptide Y, synthesized in
      neurons of the hypothalamic arcuate nucleus and released in the paraventricular
      nucleus, stimulates feeding and inhibits brown adipose tissue activity. The
      neuropeptide Y neurons are overactive in fatty Zucker rats and are thought to
      contribute to hyperphagia, reduced energy expenditure and obesity. We have
      examined the relationship between thermogenic activity in brown adipose tissue
      (measured as uncoupling protein messenger RNA levels) and hypothalamic
      neuropeptide Y and neuropeptide Y messenger RNA levels in response to cold
      exposure (4 degrees C) for 2.5 and 18 h, in fatty and lean Zucker rats. In lean
      Zucker rats, cold exposure at 4 degrees C for 2.5 and 18 h significantly
      increased uncoupling protein messenger RNA levels by 3.5-fold (P<0.01) and 3.3
      fold (P<0.01), respectively, compared with warm-maintained controls. Exposure to
      cold for 18 h also increased neuropeptide Y concentrations in the paraventricular
      nucleus (P<0.01) and ventromedial nucleus (P<0.001) in lean rats, with no change
      in neuropeptide Y messenger RNA after either 2.5 or 18 h. By contrast, fatty
      Zucker rats showed no significant changes in uncoupling protein messenger RNA
      (P>0.05) at either duration of cold exposure. There were also no significant
      changes in neuropeptide Y levels in any region nor in neuropeptide Y messenger
      RNA, with cold exposure for either period (P>0.05). In lean rats, cold exposure
      therefore stimulates brown fat uncoupling protein messenger RNA and also
      increases neuropeptide Y concentrations in its hypothalamic sites of release. We
      suggest that increased brown fat thermogenic capacity induced by cold in lean
      rats may be mediated, at least in part, by decreased neuropeptide Y release in
      the paraventricular nucleus, resulting in its accumulation in this site.
      Defective thermogenic responses in fatty rats may result from central
      dysregulation of brown adipose tissue due to sustained and non-suppressible
      overactivity of hypothalamic neuropeptide Y neurons.

PMID- 9252239
TI  - Sex hormones enhance the impact of male sensory cues on both primary and
      association cortical components of visual and olfactory processing pathways as
      well as in limbic and hypothalamic regions in female sheep.
AB  - Differential activation of neural substrates was investigated in female sheep
      exposed to a male when they were in oestrus, and sexually receptive and attracted
      to males, as opposed to anoestrus when they were not. Changes in neuronal
      activation were visualized in ovariectomized, hormone-treated ewes by quantifying
      changes in cellular expression of c-fos messenger RNA by in situ hybridization
      histochemistry. Results showed that, while oestrus induction had no significant
      effects on c-fos expression per se, a 5-min exposure to a male significantly
      increased it in a number of primary and association cortical regions (the mitral
      and granule cell layers of the olfactory bulb, visual, somatosensory,
      orbitofrontal, piriform, cingulate and temporal cortices), the limbic system (CA1
      region of the hippocampus, subiculum, lateral septum, lateral and basolateral
      amygdala, bed nucleus of the stria terminalis) and hypothalamus (mediobasal
      hypothalamus, medial preoptic area and paraventricular nucleus) as well as the
      nucleus accumbens and mediodorsal thalamus. Intromissions did not contribute
      significantly to these c-fos changes however. In anoestrus females, exposure to a
      male only produced a small significant increase in c-fos messenger RNA expression
      in the temporal cortex inspite of receiving similar amounts of visual and
      olfactory cues from him and a number of mating attempts. These results clearly
      demonstrate that changes in sexual motivation markedly alter the neural
      processing of sensory cues from males. They also show that the hormonal induction
      of sexual attraction to males cues and the resultant stimulation of sexual
      behaviour is due not only to altered responsiveness of oestrogen-sensitive brain
      regions involved in mediating behavioural responses towards the male, but also to
      changes in primary and secondary/tertiary somatosensory, olfactory and visual
      processing regions which relay sensory information to them.

PMID- 9252240
TI  - Muscle resistance to slow ramp weakly depends on activation level.
AB  - The mechanical response of human m. flexor pollicis longus to slow (3.2
      degrees/s) linear stretch by 5.5 degrees was measured during sustained (45-60 s,
      9-13.5 p.p.s.) unfused tetanus evoked by electrical stimulation. The stiffness
      increased during unfused tetanus. At the late phase of unfused tetanus it was 1.8
      +/- 0.2 (mean +/- S.D.) times greater than at the early phase. The sensitivity of
      the isometric tension level to a short change in a stimulation frequency also
      increased. At the late phase of unfused tetanus force oscillations increased 1.2
      +/- 0.2-fold during slow stretch or shortening and immediately reached a smaller
      amplitude after the cessation of length change. This was probably related to the
      friction and thixotropy in muscles. Muscle resistance to slow ramp depended only
      weakly on activation level. In the late phase of unfused tetanus the stiffness
      per unit force was 1.5 +/- 0.4 times greater at 9-13.5 p.p.s. than at 20-25
      p.p.s. Thus, the relative value of muscle stiffness was greater for smaller
      activation levels typical for maintenance of posture. The enhancement of muscle
      stiffness during sustained unfused tetanus and a weak stiffness dependence on the
      activation level indicated a non-additivity of processes occurring in active
      muscle.

PMID- 9252241
TI  - Pressure stimulates proliferation and DNA synthesis in rat intestinal epithelial
      cells.
AB  - Effects of intraluminal pressure on cultured intestinal epithelial cells were
      assessed by measuring cell proliferation and DNA synthesis after exposure to
      various pressures. Pressures of 40 to 120 mm Hg promoted cell proliferation and
      DNA synthesis. Pressure-induced DNA synthesis was further enhanced by the
      addition of interleukin-2, suggesting the regulation of intestinal epithelial
      growth by pressure in coordination with cytokines. Pretreatment with either a
      phospholipase C inhibitor or protein kinase C inhibitor significantly inhibited
      DNA synthesis promoted by pressure and interleukin-2. This study demonstrates a
      novel mechanism whereby pressure regulates cell growth in intestinal epithelial
      cells, possibly via activation of phospholipase C and protein kinase C.

PMID- 9252242
TI  - Vasodilator effect of insulin on the microcirculation of the rat cremaster
      muscle.
AB  - We recently showed that, in conscious rats, acute infusions of insulin (10-15
      fold increase in plasma insulin) produced decreases in hindquarter vascular
      resistance, but only if, changes in sympathetic outflow were prevented with a
      ganglionic blocker. The aim of the present investigation was to determine if
      similar effects of insulin could be observed in a preparation that allowed direct
      visualization of striated muscle (cremaster) microvessels. Initial studies with
      topical application of insulin showed that third-order arterioles (A3), but not
      first- or second-order arterioles vasodilated in response to 800 microU/ml and 8
      mU/ml of insulin. Systemic (euglycemic) infusion of insulin (6 mU/ml, but not 2
      mU/ml) also increased A3 arteriole diameter in animals treated with a ganglionic
      blocker, but not in control rats. These data show that insulin can have a direct
      vasodilator effect on striated muscle microvessels if concomitant increases in
      sympathetic outflow are absent. However, the response was only present with
      supraphysiological doses of the hormone.

PMID- 9252243
TI  - TGF-beta1 selectively suppresses PDGF receptor signaling pathways in MG-63 human
      osteosarcoma cell.
AB  - We previously found that TGF-beta1 inhibits PDGF mitogenicity in MG-63 cells and
      the inhibition is correlated with a suppression of the PDGF-induced receptor
      autophosphorylation. In this study, we analyze if all the PDGF receptor signaling
      pathways are similarly affected by the TGF-beta1 pretreatment. We show that TGF
      beta1 suppresses PDGF-stimulated tyrosine phosphorylation of PLC-gamma1, and the
      phosphorylation of Erk. In contrast, the tyrosine phosphorylation of PI3-kinase
      is not affected. Thus, TGF-beta1 selectively suppresses two out of three PDGF
      receptor signaling pathways despite of its prominent inhibition of the PDGF
      induced receptor autophosphorylation. The results also indicate that activation
      of the PI3-kinase pathway alone by PDGF is not sufficient in supporting the
      optimum growth of MG-63 cells under the culture conditions employed.

PMID- 9252244
TI  - Interleukin-6, tumor necrosis factor and corticosterone induction by central
      lipopolysaccharide in aged rats.
AB  - Age-related changes of the immune-adrenal axis were studied in rats treated
      intracerebroventricularly with lipopolysaccharide (LPS, 2.5 microg/5 microl).
      Serum interleukin-6 (IL-6), tumor necrosis factor (TNF) and corticosterone levels
      were evaluated in young (3 months) and old (24 months) Sprague-Dawley rats at
      different time-points. Old rats showed higher IL-6 levels compared to young rats
      while no change was observed on TNF levels in the two age groups. Corticosterone
      increase induced by LPS was lower in old than in young rats. The results show
      that heterogeneous modifications of the immune-adrenal axis occur that could have
      a pathophysiological role in the altered response to brain infections during
      aging.

PMID- 9252245
TI  - The impact of beta-adrenergic blockade on daily rhythms of melatonin and body
      temperature of golden spiny mice Acomys russatus.
AB  - Beta-adrenergic stimulation induces melatonin synthesis and non-shivering
      thermogenesis (NST) in rodents. The golden spiny mouse, Acomys russatus is a
      nocturnal species capable of diurnal activity when coexisting with its congenitor
      the common spiny mouse A. cahirinus. We have investigated the impact of beta
      adrenergic blockade on 6-sulphatoxymelatonin (6-SMT--a metabolite and index of
      melatonin production) and body temperature (Tb) daily rhythms in male A.
      russatus. Mice were acclimated to an ambient temperature (Ta) of 28 degrees C,
      under two photoperiod regimes (16L:8D; 8L:16D). The daily rhythms of Tb and
      urinary 6-SMT were measured for a period of 30 h at intervals of 4 h. Propranolol
      (4.5 mg/kg, i.p.) was administered one hour before lights went off (i.e. when
      beta blockade does not affect NST in this species) and both variables were
      measured for another 30 h. The beta blocker markedly augmented melatonin output
      of A. russatus under both photoperiod regimes. The elevation in melatonin
      secretion was accompanied with an increase in Tb of only 16L:8D-acclimated mice
      (i.e. shorten duration of melatonin peak). However, in 8L:16D-acclimated mice, a
      phase advance of about 4 h was noted in 6-SMT daily rhythm. These results
      indicate that the role of sympathetic innervation in regulation of melatonin
      synthesis in A. russatus differs from that in the rat. In addition, these data
      are compatible with the hyperthermic action of melatonin in this species.
      Therefore, it is suggested that in A. russatus, other neural pathways are
      involved in its pineal regulation.

PMID- 9252246
TI  - Ca2+/phospholipid-binding and syntaxin-binding of native synaptotagmin I.
AB  - Synaptotagmin, a synaptic vesicle protein endowed with multiple properties, is
      the putative calcium sensor in neuroexocytosis. Ca2+/phospholipid binding and
      syntaxin binding activity of synaptotagmin were previously investigated using
      recombinant fusion proteins. In phospholipid binding the EC50 for calcium
      obtained was different when fusion proteins containing one (C2A) or both
      (C2A+C2B) binding domains were used. It was alternatively proposed that one or
      both synaptotagmin binding domains are important for calcium-sensing and
      triggering of transmitter release. In this study the binding activity of native
      full-length synaptotagmin, immobilized on beads, was investigated. We found the
      kinetic parameters of Ca2+/phospholipid binding to be compatible with the role of
      calcium sensor for synaptotagmin (EC50 for calcium = 72 +/- 7 microM), with the
      two C2 domains supporting separate and complementary calcium sensing properties.
      The binding of native syntaxin to synaptotagmin was measurable in the absence of
      calcium, but was markedly stimulated (2.2-fold) in the presence of mM calcium. It
      may be speculated that the two domains have a synergistic action in fast
      synchronous transmitter release, whereas C2B domain alone may support slow
      asynchronous release, working as a high affinity calcium sensor.

PMID- 9252247
TI  - Enhanced synthesis of proteoglycans by vascular endothelial cells treated with
      phorbol ester.
AB  - We investigated the biosynthesis of proteoglycans (PG) in endothelial cells
      following their treatment with phorbol 12-myristate 13-acetate (PMA). Confluent
      cultures of bovine aortic endothelial cells were incubated in the presence and
      absence of PMA (100 ng/ml) and then pulsed with [35S]sulfate, [3H]glucosamine, or
      [35S]sulfate plus [3H]leucine for varying times in the absence of PMA.
      Alternatively, confluent endothelial cells were simultaneously incubated with PMA
      and [35S]sulfate for varying times. The metabolically labeled PG in the cell
      layer and medium were analyzed. Both short-term and prolonged exposure of
      endothelial cells to PMA significantly stimulated PG synthesis, regardless of the
      experimental conditions. [35S]sulfate incorporation into newly synthesized PG in
      PMA-treated cells also increased by 1.7-fold and 3.6-fold over control cells,
      following a 15-min and 30-min pulse, respectively. Cycloheximide markedly
      inhibited the increased synthesis of PG in PMA-treated cells, while actinomycin D
      produced a moderate inhibition. PG secretion was increased in PMA-treated cells
      compared with control cells, while there was no significant difference in PG
      degradation between the two cultures. PG from control and PMA-treated endothelial
      cell cultures did not differ in composition or hydrodynamic sizes. The
      incorporation of [3H]leucine into total cellular proteins decreased significantly
      following exposure of endothelial cells to PMA. Endothelial cells exposed to PMA
      for 3 h had significantly more protein kinase C (PKC) activity than did control
      cells. Inhibition of PKC by calphostin C abolished the PMA-mediated stimulation
      of PG synthesis in endothelial cells. The results indicate that PMA stimulates PG
      synthesis in endothelial cells either directly or indirectly through a PKC
      dependent mechanism.

PMID- 9252248
TI  - Acceleration of oxidative stress-induced endothelial cell death by nitric oxide
      synthase dysfunction accompanied with decrease in tetrahydrobiopterin content.
AB  - The purpose of this study was to examine whether nitric oxide (NO) synthase
      dysfunction accompanied with decrease in tetrahydrobiopterin (BH4) content
      increases H2O2-induced endothelial cell death. Endothelial cell death was
      measured by the release of intracellular lactate dehydrogenase (LDH).
      Intracellular BH4 content was changed by pretreatment with 2,4-diamino-6
      hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, or pretreatment
      with sepiapterin, a substrate for the salvage pathway of BH4 synthesis, and the
      intracellular content was measured by high performance liquid chromatography
      equipped with a fluorescence detector. Moreover, production of superoxide was
      detected by a chemiluminescence technique using MCLA, a Cypridina luciferin
      analogue, for the superoxide-sensitive probe. Pretreatment with DAHP (10 mM) for
      24 h decreased intracellular BH4 content to 14% and increased H2O2-induced cell
      death. The toxic effect of DAHP was reduced by co-pretreatment with sepiapterin
      (100 microM) or treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mM),
      an inhibitor of NO synthase, but not by N(G)-methyl-L-arginine (L-NMA, 1 mM), the
      other inhibitor of NO synthase. Moreover, production of superoxide in endothelial
      cells induced by Ca2+-ionophore ionomycin (1 microM) increased by the
      pretreatment with DAHP, and the increase in superoxide production was blocked by
      L-NAME (1 mM) but not L-NMA (1 mM). Co-pretreatment with sepiapterin decreased
      the production of superoxide. These findings suggested that dysfunction of NO
      synthase with a decrease in BH4 content in endothelial cells produced superoxide
      instead of NO and increased the oxidative stress-induced endothelial cell death.

PMID- 9252249
TI  - Complement consumption by poly(ethylene glycol) in different conformations
      chemically coupled to poly(isobutyl 2-cyanoacrylate) nanoparticles.
AB  - There is an increasing interest to develop injectable drug polymeric carriers not
      recognizable by the body as foreign particles and eliminated very quickly from
      the bloodstream. A polyethylene glycol (PEG)-coating onto injectable particles
      showed to reduce either protein adsorption and complement consumption, as a
      function of the PEG density. In this work we compared the complement rejecting
      ability of PEG in different conformations coupled to polyisobutylcyanoacrylate
      (PIBCA) nanoparticles, through the analysis of the residual hemolytic capacity of
      the human serum after contact with the particles. Nanoparticles were formed by
      chemical coupling of PEG during emulsion/polymerization of isobutylcyanoacrylate
      (IBCA). Nanoparticles characterization included an investigation of their surface
      properties, such as hydrophilicity and conformational mobility of the PEG chains
      grafted on the nanoparticles surface, and PEG total content. The polymerization
      kinetics of IBCA in presence of PEG or MePEG were also studied. Complement
      consumption was observed to be very sensitive to the number of particles in
      contact with human serum, as well as to the PEG conformation, suggesting PEG
      configuration could affect the particle exposed surface.

PMID- 9252250
TI  - Bradykinin, lemakalim and sodium nitroprusside relax the mouse trachea in vitro
      by different mechanisms.
AB  - The role of K+ channels in the relaxations induced by bradykinin, lemakalim, an
      activator of ATP-sensitive K+ channels and sodium nitroprusside (SNP), a nitric
      oxide (NO) donor was examined in the isolated mouse trachea precontracted by
      methacholine (1 microM). 4-aminopyridine (4-AP, 0.1-2 mM), an inhibitor of 4-AP
      sensitive delayed rectifier channels, did not alter relaxations induced by
      bradykinin, lemakalim or SNP. Glibenclamide and glipizide (10-33 microM),
      inhibitors of ATP-sensitive K+ channels, inhibited relaxation to lemakalim
      without affecting responses to bradykinin and SNP. Charybdotoxin (10-100 nM) and
      iberiotoxin (10-100 nM), inhibitors of large conductance Ca2+-activated K+
      channels, failed to inhibit relaxation to bradykinin, lemakalim or SNP. Apamin
      (0.1-1 microM), an inhibitor of small conductance Ca2+-activated K+ channels, did
      not alter responses to bradykinin, lemakalim and SNP. The results implicate that
      the mechanism of relaxation induced by bradykinin and SNP is different from that
      of lemakalim. Relaxation of the isolated mouse trachea by lemakalim appears to be
      mediated by ATP-sensitive K+ channels. Bradykinin and SNP induced relaxations are
      not mediated via Ca2+-activated K+ channels.

PMID- 9252251
TI  - Differential effects of flavonoids on testosterone-metabolizing cytochrome P450s.
AB  - Flavonoids are widely distributed phytochemicals, whose modulation of cytochrome
      P450 mediated carcinogen metabolism is well established. Less well studied is
      their effect on P450 dependent metabolism of endogenous substrates. To address
      this question we evaluated a series of twelve flavonoids and hematoxylin for
      their effect on P450-mediated steroid hydroxylation by rat liver microsomes. Site
      specific 7alpha-, 6beta- and 2alpha-hydroxylation of testosterone by P450s 2A1,
      3A2 and 2C11, respectively, was measured. Highly selective patterns of inhibition
      or activation of these P450s were observed. 3,6-dichloro-2'-isopropyloxy-4'
      methylflavone was the most potent inhibitor of P450 2C11 while cyanidin chloride
      most potently inhibited P450s 2A1 and 3A2. The flavonoid analogue hematoxylin was
      unique in that it activated 2C11 (by 2.5 fold) yet inhibited both 2A1 and 3A2 (by
      60%). These results indicate that consumption of dietary flavonoids may likewise
      alter the metabolite profile of steroids and other physiological P450 substrates.

PMID- 9252252
TI  - [Met5]enkephalin and delta2-opioid receptors in the spinal cord are involved in
      the cold water swimming-induced antinociception in the mouse.
AB  - Mice made cold water swimming (CWS: 4 degrees C, 3 min) produced an opioid
      mediated antinociception. Experiments were designed to determine what types of
      opioid receptors and endogenous opioid peptides in the spinal cord are involved
      in the CWS-induced antinociception in male ICR mice. Antinociception was measured
      by the tail-flick test. CWS-induced antinociception was blocked by intrathecal
      (i.t.) pretreatment with antiserum to [Met5]enkephalin (100 microg, 1 hr), but
      not by antiserum (100 microg, 1 hr) to [Leu5]enkephalin, beta-endorphin or
      dynorphin A (1-17). Moreover, i.t. pretreatment with delta2-opioid receptor
      antagonist naltriben (NTB: 10 microg, 10 min) blocked the antinociception induced
      by CWS or i.t.-administered [Met5]enkephalin (10 microg). However, the
      antinociception induced by CWS or i.t.-administered [Met5]enkephalin was not
      blocked by i.t. pretreatment with delta1-opioid receptor antagonist 7-benzylidene
      naltrexone (BNTX: 1 microg, 10 min), mu-opioid receptor antagonist D-Phe-Cys-Try
      D-Try-Om-Thr-Phe-Thr-NH2 (CTOP: 50 ng, 10 min), or kappa-opioid receptor
      antagonist norbinaltorphimine (norBNI: 5 microg, 24 hr). These data indicate that
      [Met5]enkephalin and delta2-opioid receptor in the spinal cord are involved in
      antinociception induced by CWS.

PMID- 9252253
TI  - Screening for novel drug effects with a microphysiometer: a potent effect of
      clofilium unrelated to potassium channel blockade.
AB  - Changes in cellular metabolism in response to pharmacological compounds can be
      detected using a biosensor known as a microphysiometer, which measures the rate
      at which cells release acidic metabolites. We have applied this technique to
      screen for effects of cation channel blockers on the metabolism of a variety of
      human and murine cell lines. At concentrations sufficient for cation channel
      blockade, most of these drugs have little or no effect on cellular metabolism as
      measured by acid release. In contrast, the potassium channel blocker clofilium
      triggers sustained increases in acid release at low (> or = 3 microM)
      concentration. Acid release persists in media containing high (150 mM)
      extracellular potassium. This release is not triggered by chemically similar
      potassium channel blockers. Thus these metabolic effects reflect a potent and
      specific function of clofilium which is unrelated to potassium channel blockade.
      Attempts to identify physiological correlates to this response revealed that low
      concentrations of clofilium but not other potassium channel blockers cause
      lymphoma apoptosis. These findings demonstrate that effects of clofilium found in
      other studies may not be due to changes in plasma membrane potassium conductance.

PMID- 9252254
TI  - Working conditions and prevalence of pre-eclampsia, Norway 1989.
AB  - OBJECTIVE: To study the associations between working conditions and pre
      eclampsia. METHODS: A cross-sectional study based on questionnaires to all
      parturients was conducted in Norway from 16 October 1989 to 26 November 1989,
      with an 87.2% response rate. Of the 5388 responders with singleton pregnancies,
      3321 continued in paid work beyond the 3rd month of pregnancy. Pre-eclampsia was
      recorded if the woman reported hospitalization for hypertension, or if
      proteinuria and hypertension were diagnosed more than once in the pregnancy.
      RESULTS: The prevalence of pre-eclampsia was increased in work involving the
      lifting of heavy loads of 10-20 kg (adjusted odds ratio (OR), 1.8; 95% CI, 1.2
      2.5), hectic work pace (OR, 1.4; 95% CI, 1.0-2.0, P < 0.05), work with hands
      above shoulder level (OR, 1.4; 95% CI, 1.0-2.2; P = 0.07) and for parous women,
      shift work (OR, 2.0; 95% CI, 1.1-3.6). It was reduced when the woman had an
      influence on work pace (OR, 0.7; 95% CI, 0.5-1.0; P = 0.07). Prevalence was also
      increased with daily consumption of more than four cups of coffee (OR, 1.6; 95%
      CI, 1.1-2.3). CONCLUSION: Prenatal care should include assessment of working
      conditions, as early improvements may reduce the risk of pre-eclampsia.

PMID- 9252255
TI  - Pregnancy-induced hypertension and hyaline membrane disease.
AB  - OBJECTIVES: (1) To determine whether the incidence of hyaline membrane disease
      (HMD) is different among premature babies of pre-eclamptic women and those of
      normotensive controls; (2) to determine the relative risk (RR) of HMD according
      to the severity of pre-eclampsia and gestational age. METHODS: A retrospective
      and prospective cohort of 271 pre-eclamptic women and 271 normotensive controls,
      with gestational age between 28 and 34 weeks was studied, including only
      singleton pregnancies, live fetuses and well-documented gestational age.
      Exclusion criteria were ruptured membranes > 24 h, other maternal diseases and
      previous use of corticosteroids. Statistical analysis included relative risk and
      multiple logistic regression model. RESULTS: The RR of HMD for babies of pre
      eclamptic women was 0.96 (95% CI: 0.78-1.17), and remained unchanged after
      controlling for gestational age and multiple logistic regression analysis.
      CONCLUSION: Preterm babies of pre-eclamptic mothers had the same probability of
      having HMD as newborns of normotensive mothers.

PMID- 9252256
TI  - Gestational and pre-gestational diabetes: comparison of maternal and fetal
      characteristics and outcome.
AB  - OBJECTIVE: To determine the incidence of antenatal and intrapartum maternal and
      fetal complications of gestational diabetes mellitus (GDM) and compare them with
      pre-gestational diabetes mellitus (pre-GDM) and non-diabetic pregnancies in our
      population. STUDY DESIGN: Nine-hundred and seventy-two women with gestational
      diabetes mellitus and 71 women with pre-gestational diabetes mellitus, and their
      offspring (delivered in our hospital between January 1991 and April 1994) were
      studied. Maternal and fetal prenatal and intrapartum complications were analyzed.
      RESULTS: The incidence of GDM was 9.8%. The maternal complications included
      higher incidences of cesarean section and perineal lacerations in GDM and pre-GDM
      patients than in the non-diabetic pregnancies, and higher rates of macrosomia and
      hypoglycemic episodes in their offspring. CONCLUSION: The incidence of maternal,
      fetal and neonatal complications in GDM is similar to pre-GDM patients and their
      offspring. Both GDM and pre-GDM pregnancies and the offspring should, therefore,
      be monitored and managed identically.

PMID- 9252257
TI  - Puerperal tetanus and hysterectomy.
AB  - OBJECTIVES: To compare the clinical course and outcome of patients with post
      partum tetanus (n = 21) to those of non-post-partum ones (n = 24) and to
      determine the effect of early hysterectomy on the survival of cases with severe
      post-partum tetanus (n = 20). METHODS: In this prospective study we compared the
      clinical course and outcome of post-partum and non-post-partum cases of tetanus
      admitted to the intensive care unit. Moreover, early hysterectomy was done on
      every other patient with severe post-partum tetanus (n = 10). Chi-square and
      Student's t-tests were used for statistical purposes. RESULTS: Post-partum cases
      were younger (P = 0.002), had a higher incidence of acute respiratory failure and
      a mortality rate compared to the non-post-partum group. In addition, early
      hysterectomy did not change the course of severe post-partum cases. CONCLUSION:
      The mortality associated with post-partum tetanus is comparable to non-post
      partum cases and early hysterectomy has no effect on its outcome.

PMID- 9252258
TI  - Ultrasonographic detection of single umbilical artery: a simple marker of fetal
      anomaly.
AB  - OBJECTIVE: To detect associated anomalies, karyotypes and perinatal prognosis of
      fetuses with single umbilical artery. METHOD: Fifteen fetuses who have single
      umbilical artery were evaluated in the obstetrical ultrasonography and medical
      genetics departments of Osmangazi University. RESULTS: Fifteen fetuses with
      single umbilical artery were detected during antenatal ultrasonographic
      examinations. Associated sonographic abnormalities include oligohydramnios (two),
      intrauterine growth retardation (one), renal agenesis (one), fetal ascites (one),
      diaphragmatic hernia (one), hydrocephalus (two), and meningomyelocele (one).
      Complications related to the pregnancy were pre-eclampsia in one case and
      abruptio placenta in another. Karyotype analysis was available in 11 cases and
      the only cytogenetic abnormality detected was trisomy 18 in one case. Two cases
      with hydrocephalus and single umbilical artery were delivered by cesarean section
      at 34 and 38 weeks, but both died (on the first and fifth days after birth). Five
      pregnancies were terminated because of intrauterine death (one), severe pre
      eclampsia (one), cytogenetic abnormality (one), and multiple congenital anomalies
      associated with single umbilical artery (two) at 36, 27, 22, 26 and 29 weeks,
      respectively. Eight of the neonates who had no additional congenital or
      cytogenetic abnormality were completely normal at birth and during the neonatal
      period. Diagnoses were confirmed pathologically in all cases. CONCLUSION:
      Scanning the umbilical cord should be one of the essential parts of
      ultrasonographic examination. When single umbilical artery is detected, a
      detailed ultrasonographic examination is necessary to rule out associated
      abnormalities. We advise fetal karyotyping even when no additional pathology can
      be detected on ultrasonographic examination.

PMID- 9252259
TI  - Subcutaneous transposition of the ovary following hysterectomy.
AB  - OBJECTIVES: Preservation of ovarian function at hysterectomy in pre-menopausal
      women is desirable. A possibly malignant tumor from retained ovary is a concern.
      We demonstrate a new technique for exteriorization of the ovaries. METHOD: In 27
      patients, the infundibulopelvic ligament was mobilized. The retroperitoneal space
      was then widely opened. The ovary was gently pulled through a fascial incision
      and fixed on the fascia followed by skin closure. RESULTS: Cystic formation was
      common (66.7%). Four patients had extreme enlargement of the transposed ovary. A
      needle puncture revealed intra-ovarian hematomas or fluid retention. One had
      puncture of the translocated ovary for in vitro fertilization more than two years
      following transposition. CONCLUSIONS: Possible advantages are (1) early detection
      and diagnosis of ovarian cysts, (2) easy surgical access to remove ovarian cysts,
      (3) transposition of ovaries outside the radiation field and (4) in vitro
      fertilization is facilitated. Comparative study for ovarian function is ongoing.

PMID- 9252260
TI  - Fertility and pregnancy in inflammatory bowel disease.
AB  - OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged
      16-45 years during the 20-year period 1967-1986, was carried out in North East
      Scotland. METHOD: Five-hundred and three women were identified: 15 patients had
      died from unrelated causes and 22 had emigrated, but 409 of the remaining 466
      patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative
      colitis and Crohn's disease had normal fertility when compared with the general
      population of north east Scotland. However, unresolved infertility problems were
      more frequent in women who had undergone surgery for inflammatory bowel disease
      compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for
      ulcerative colitis). Disease relapse rates did not increase in pregnancy.
      CONCLUSIONS: Overall, at conception women with active disease were as likely to
      have a normal full-term pregnancy as those in remission. However, spontaneous
      abortion occurred in five (36%) pregnancies of women who had undergone previous
      surgery for Crohn's disease and had evidence of recurrent disease. Three of these
      pregnancies were associated with active disease.

PMID- 9252261
TI  - Increasing baseline intrauterine pressure associated with impending spontaneous
      uterine rupture.

PMID- 9252262
TI  - Trial of labor after cesarean birth in Iraq.

PMID- 9252263
TI  - Prevalence of hepatitis B surface antigen in pregnant Lebanese women.

PMID- 9252264
TI  - Clinical features of hepatitis C virus (HCV) infection in pregnancy.

PMID- 9252265
TI  - Live infant salvaged from a ruptured cornual (interstitial) pregnancy at 33-weeks
      gestation.

PMID- 9252266
TI  - The use of a Sengstaken-Blakemore tube to control post-partum hemorrhage.

PMID- 9252267
TI  - Verres needle as an auxiliary instrument for mobilization of fallopian tubes and
      ovaries in diagnostic microlaparoscopy.

PMID- 9252268
TI  - ACOG committee opinion. Guidelines for relationships with industry. Number 182,
      April 1997 (replaces no. 45, October 1985). Committee on Ethics. American College
      of Obstetricians and Gynecologists.

PMID- 9252269
TI  - ACOG committee opinion. Routine storage of umbilical cord blood for potential
      future transplantation. Number 183, April 1997. Committee on Obstetric Practice.
      American College of Obstetricians and Gynecologists.

PMID- 9252270
TI  - Analysis of transcription by RNA polymerase II in vitro.

PMID- 9252271
TI  - Studies of an Isolated 15 N-15 N Spin Pair. Off-Angle Fast-Sample-Spinning NMR
      and Self-Consistent-Field Calculations for Diazo Systems
AB  - An off-magic-angle spinning study of the nonassociated molecular solid, doubly 15
      N-labeled 5-methyl-2-diazobenzenesulphonic acid hydrochloride (I ) is reported.
      The validity of the off-magic-angle spinning approach under fast-spinning
      conditions is verified by average Hamiltonian theory. Ab initio SCF calculations
      were performed on the simpler molecule, C6 H5 N2 + , to provide the shielding
      parameters, the dipolar coupling between the two nitrogen nuclei, and the
      electric field gradient existing at both the alpha-nitrogen and beta-nitrogen
      sites. The calculated values are in good agreement with the shielding and
      effective dipolar coupling data elucidated in the present investigation, and with
      a previous study of the two singly 15 N-labeled isotopomers in which information
      concerning the electric field gradient at the alpha and beta sites was deduced.

PMID- 9252272
TI  - Mutual Inductance in the Bird-Cage Resonator
AB  - Formulas are derived to account for the effect of the mutual inductances, between
      all meshes, upon the electrical resonance spectra bird-cage resonators, and
      similar structures such as the TEM resonator of P. K. H. Roschmann (United States
      Patent 4,746,866) and J. T. Vaughan et al. (Magn. Reson. Med. 32, 206, 1994). The
      equations are parameterized in terms of isolated mesh frequencies and coupling
      coefficients, and ought therefore apply not only to simple magnetic couplings
      used in the derivation, but to electromagnetic couplings as well. A method for
      measuring the coupling coefficients-applicable to shielded as well as unshielded
      resonators-is described, based upon the splitting of frequencies in pairs of
      coupled resonators; and detailed comparisons are given between calculated and
      measured resonance spectra: for bird-cage resonators, with and without shields,
      and for the TEM resonator.

PMID- 9252273
TI  - Shielding of Low-Frequency Magnetic Interference in Weak-Field MRI by a Single
      Layer Cylindrical Coil
AB  - Shielding of detection coil from low-frequency magnetic-field interference is one
      of the main problems in weak-field MRI methods that utilize cycling of main
      magnetic field (MRI in the Earth's magnetic field, for example). In such cases,
      the best solution is usually to shield the detection coil by shorting one of the
      resistive coils of the system, typically the magnetization coil. The optimization
      of this shielding method has been done by studying the total magnetic field on
      the axis of a shorted single-layer cylindrical coil placed in a homogeneous
      oscillating magnetic field parallel to the coil axis. The results are generalized
      for the case when series impedance is added to the shielding coil. The optimal
      added impedance that gives the largest shielding factor in the center of the coil
      is calculated. Because the theoretical treatment is confined to the coil axis,
      the results are in simple form ready to use in applications. The results of the
      calculation are verified experimentally and implemented in Earth's field MRI
      system.

PMID- 9252274
TI  - Sample-Induced RF Perturbations in High-Field, High-Resolution NMR Spectroscopy
AB  - Conducting dielectric samples are often used in high-resolution experiments at
      high field. It is shown that significant amplitude and phase distortions of the
      RF magnetic field may result from perturbations caused by such samples.
      Theoretical analyses demonstrate the spatial variation of the RF field amplitude
      and phase across the sample, and comparisons of the effect are made for a variety
      of sample properties and operating field strengths. Although the effect is highly
      nonlinear, it tends to increase with increasing field strength, permittivity,
      conductivity, and sample size. There are cases, however, in which increasing the
      conductivity of the sample improves the homogeneity of the amplitude of the RF
      field across the sample at the expense of distorted RF phase. It is important
      that the perturbation effects be calculated for the experimental conditions used,
      as they have the potential to reduce the signal-to-noise ratio of NMR experiments
      and may increase the generation of spurious coherences. The effect of RF-coil
      geometry on the coherences is also modeled, with the use of homogeneous
      resonators such as the birdcage design being preferred. Recommendations are made
      concerning methods of reducing sample-induced perturbations. Experimental high
      field imaging and high-resolution studies demonstrate the effect.

PMID- 9252275
TI  - NMR Relaxation Mechanisms for Backbone Carbonyl Carbons in a 13 C, 15 N-Labeled
      Protein
AB  - The predominant relaxation mechanisms for backbone carbonyl carbon (13 C')
      relaxation in a 13 C, 15 N-doubly enriched sample of the thermostable Sso7d
      protein have been investigated. Pulse sequences for measurements of longitudinal
      and transverse 13 C' relaxation rates were implemented, and these rates were
      measured at magnetic fields of 11.7 and 14.1 T. The field dependence in measured
      rates is small and consistent with a predominant contribution from chemical-shift
      anisotropy (CSA) to 13 C' relaxation. A pulse sequence for measurement of {1 H}
      13 C' cross-relaxation rates (steady-state NOEs) was also developed. This
      experiment reveals a significant NOE between protons and all 13 C', indicating
      that dipolar interactions between these nuclei contribute to 13 C' relaxation.
      Experiments designed to suppress cross correlation between CSA relaxation and
      dipole-dipole (DD) relaxation due to neighboring 13 Calpha indicate that this
      effect is negligible. A more quantitative treatment is also presented, in which
      backbone dynamics parameters are fitted to average 13 C' relaxation rates using
      Lipari-Szabo expressions for the spectral density. This fit, which reproduces
      well expected backbone dynamics parameters for a folded protein, is used to
      estimate the relative contributions of various mechanisms to 13 C' relaxation. It
      is found that both longitudinal and transverse relaxation rates are dominated by
      CSA relaxation and contain significant contributions due to DD relaxation induced
      by nearby protons. Contributions from DD relaxation due to covalently bound 13
      Calpha and 15 N are comparably small. The predominant effects of CSA and 1 H-13
      C' DD interactions, for which physical and geometrical parameters are uncertain,
      complicate the use of 13 C' relaxation as a sequence-specific probe for protein
      backbone dynamics.

PMID- 9252276
TI  - New Aspects of Spin Diffusion and Cross Relaxation in Solid-State NMR
AB  - Theoretical models for motionally driven spin diffusion are compared and applied
      to spins S = (1/2) and S = 1. Their predictions are quantitatively corroborated
      by experiments on a single crystal of deuterated biphenyl. In this system, a
      molecular flip process drives spin diffusion and makes it strongly temperature
      dependent. In the second part, it is shown how spin diffusion of quadrupolar
      order degenerates into cross relaxation. A single crystal of partially deuterated
      durene provides a clear-cut example of cross relaxation in a dipolar coupled pair
      of spins S = 1. This observation explains why, in solids, the relaxation time of
      quadrupolar order, T 1Q , is often much shorter than T 1 .

PMID- 9252277
TI  - ESR Study of Electron-Nuclear Dipolar Relaxation for AsO4 4- Spin Probe in the
      Paraelectric Phase of KH2 AsO4
AB  - Saturation behavior of allowed and forbidden ESR transition of AsO4 4-
      paramagnetic probe in KH2 AsO4 was studied in the wide temperature interval
      around the paraelectric-ferroelectric phase transition, T c . The ratios between
      forbidden and allowed line intensities were employed to deduce information on the
      electron-nuclear dipolar (END) relaxation mechanism. It was shown that a proton
      END relaxation mechanism exhibits an extremal temperature behavior in the
      paraelectric phase around 230 K. The extremal temperature behavior was described
      by employing a model of proton hopping along the O-H...O bonds around the
      paramagnetic centers, and the correlation time of this hopping was estimated in
      the wide temperature range in the paraelectric phase (150-330 K). The temperature
      dependence of effective proton distance from the neighbor oxygens was obtained,
      and it was discussed in terms of a localization of the spin density on these
      oxygens caused by charge inbalance in the As-O bonds in the ferroelectric phase.

PMID- 9252278
TI  - Dynamic Hydrogen Disorder in Solid Tropolone. A Single-Crystal NMR Study of the
      Hydroxyl Deuterons
AB  - The orientation and temperature dependences of the deuterium NMR spectrum and
      spin-lattice relaxation time of the hydroxyl deuterons in single crystals of
      tropolone-d 1 are reported. The results are interpreted in terms of a dynamic
      hydrogen disorder model in which the hydrogen nuclei move in an asymmetric double
      well potential. According to this model, the hydrogen-bonded dimer structure as
      determined by X-ray diffraction constitutes a majority species in the tropolone
      crystal, comprising more than 98% of the molecules at room temperature. However,
      there also exists a tautomeric minority species formed by a concerted back and
      forth shifting of the hydroxyl hydrogens (deuterons) along the hydrogen bonds to
      the nearby carbonyl oxygens. This process results in a modulation of the electric
      field gradient tensor at the site of the deuterons, thus providing an efficient
      relaxation mechanism. The concentration of the minority species is too low and
      its lifetime is too short to make its direct observation possible. Still,
      structural information about this species and kinetic and thermodynamic
      parameters of the hydrogen shift process can be derived by fitting the measured T
      1 values to the above model.

PMID- 9252279
TI  - In Vitro Validation of Rapid MR Measurement of Wave Velocity
AB  - A one-dimensional time-of-flight MR sequence, having a total acquisition time of
      approximately 60 ms, has been employed to determine flow-wave propagation
      velocities for pulsatile flow in compliant latex tubes. The results were compared
      with those of two independent methods and were found to be in good agreement. An
      extension of the same MR method was used to test the validity of the "water
      hammer" relationship as a means to assess pulse pressure. Very good agreement was
      found with direct manometric determinations of pulse pressure.

PMID- 9252280
TI  - "Kin " HEHAHA Sequences, Heteronuclear Hartmann-Hahn Transfer with Different
      Bandwidths for Spins I and S
AB  - A new class of heteronuclear Hartmann-Hahn experiments that is based on the
      simultaneous irradiation of two different multiple-pulse sequences is introduced.
      For these "kin " HEHAHA sequences, the scaling properties of the effective
      heteronuclear coupling constants are analyzed. Four kin sequences are presented
      with a ratio of the active bandwidths DeltanuI /DeltanuS ranging between 1/2 and
      1/10. The offset dependence of the polarization-transfer efficiency is examined
      experimentally and with the help of numerical simulations.

PMID- 9252281
TI  - A High-Resolution 3D Separated-Local-Field Experiment by Means of Magic-Angle
      Turning
AB  - A 3D separated-local-field (SLF) experiment based on the 2D PHORMAT technique is
      described. In the 3D experiment, the conventional 2D SLF powder pattern for each
      chemically inequivalent carbon is separated according to their different
      isotropic chemical shifts. The dipolar coupling constant of a C-H pair, hence the
      bond distance, and the relative orientation of the chemical-shift tensor to the C
      H vector can all be determined for the protonated carbons with a single
      measurement. As the sample turns at only about 30 Hz in a MAT experiment, the SLF
      patterns obtained approach those of a stationary sample, and an accuracy in the
      measurement similar to that obtained on a stationary sample is expected. The
      technique is demonstrated on 2,6-dimethoxynaphthalene, where the 13 C-1 H
      separated-local-field powder patterns for the six chemically inequivalent carbons
      are clearly identified and measured. The observed dipolar coupling for the
      methoxy carbon is effectively reduced by the fast rotation of the group about its
      C3 symmetry axis. The average angle between the C-H bond direction and the C3
      rotation axis in the OCH3 group is found to be about 66&deg;.

PMID- 9252282
TI  - A Pulse Sequence for Flow Evaluation Based on Self-Refocused RF and Interleaved
      Spiral Readout

PMID- 9252283
TI  - Real-Time Response and Phase-Sensitive Detection to Demonstrate the Validity of
      ESR-STM Results

PMID- 9252284
TI  - Retrieving 31 P Chemical-Shift-Tensor Information for Dihydrogen Phosphates in
      the Presence of Homonuclear 31 P-31 P Dipolar Coupling

PMID- 9252285
TI  - A Method to Observe NOE from Regions of Spectral Overlap. Nuclear-Overhauser
      Enhanced J -Resolved Difference Spectroscopy

PMID- 9252286
TI  - Short-Time PFGSTE Diffusion Measurements

PMID- 9252287
TI  - How to Reduce the Residual H2 O Signal in the PFG DQ Experiments Recorded with
      Only z Gradients

PMID- 9252288
TI  - Removal of Systematic Errors Associated with Off-Resonance Oscillations in T2
      Measurements

PMID- 9252289
TI  - Symmetry Analysis of the Vibrational Dynamics of the H3 D2 + and H2 D3 +
      Complexes
AB  - A symmetry analysis of the H3 D2 + and H2 D3 + complexes in a model with one
      large amplitude motion, the propeller-like internal rotation, is presented.
      Symmetry coordinates and symmetry adapted polynomial expansions of the potential,
      dipole moment, and polarizability functions are derived within the framework of
      the extended molecular symmetry group G 3 (2, 2) using the projection operator
      and Molien function techniques.

PMID- 9252290
TI  - Vibrational Dynamics of H5 + and Its Deuterated Isotopomers
AB  - The vibrational dynamics of the H5 + complex and its deuterated isotopomers H4 D+
      , H3 D2 + , H2 D3 + , HD4 + , and D5 + are investigated using a model Hamiltonian
      which is based on the assumption that on the potential energy hypersurface the
      barriers for the internal rotation motions are infinitely high except for the
      practically free propeller-like motion. According to our previous studies on H5 +
      , the propeller-like rotation essentially does not interact with the remaining
      vibrations and is therefore neglected in the present calculations. Within the
      framework of the adiabatic approximation the resulting eight-dimensional
      vibrational problem is separated into two smaller subproblems which are solved
      numerically applying the same scheme as previously. The calculations are
      performed using a new extended potential energy function which also provides a
      reliable description of the interactions between the degenerate stretching
      motions and the remaining vibrations. As in our previous calculations, the high
      frequency fundamentals obtained for H5 + are in good agreement with their
      experimental counterparts, whereas the reliability of the present results for the
      low-frequency motions is considerably improved as a result of the appropriate
      description of the relevant interactions. Predictions of the vibrational energies
      of the other deuterated isotopomers are made on the same accuracy level. The zero
      point energies derived from the present calculations are believed to be accurate
      enough for a quantitative determination of the binding energies of the different
      isotopomers.

PMID- 9252291
TI  - High Resolution IR Study of the Coriolis Coupling between nu3 and nu9 in CH2 35
      Cl37 Cl
AB  - The infrared spectra of the nu3 and nu9 bands of methylene chloride have been
      recorded both for isotopically pure CH2 35 Cl2 and for a natural mixture with a
      resolution of 0.0025-0.004 cm-1 (FWHM) in the range 600-800 cm-1 using a Bruker
      IFS 120 HR Fourier Transform interferometer. The Coriolis coupling between the
      two CCl2 stretching fundamentals nu3 and nu9 has been investigated for the CH2 35
      Cl37 Cl isotopic species. An effective coupling constant xi39 c = 0.1975(2) cm-1
      results from a full rotational analysis of a difference spectrum, obtained by
      subtracting the CH2 35 Cl2 room temperature spectrum from that of the natural
      mixture. A least-mean-squares fit of the data to Watson's A-reduction Hamiltonian
      in the Ir representation yields a set of accurate effective rotational and
      distortion constants up to quartic terms for the excited states of both
      fundamental bands. The standard deviation of the fit was 0.893 x 10(-3) cm-1 .

PMID- 9252292
TI  - Infrared Diode-Laser Molecular-Beam Spectrum of the nu2 Band of Chlorine Nitrate
      at 1293 cm-1
AB  - The nu2 band of chlorine nitrate (ClONO2 ) near 1293 cm-1 has been measured in a
      molecular beam with a diode-laser spectrometer. The low rotational temperature of
      the molecular beam, approximately 23 K, simplifies the spectrum allowing
      essentially complete assignment of the 35 Cl and 37 Cl lines. An a /b hybrid band
      is observed with the a -type transition moment being approximately a factor of 2
      larger than the b -type transition moment. An inverted shift of the band origins
      is found with the 37 Cl band origin blue shifted from the 35 Cl by +0.37 cm-1 .
      This isotopic shift is attributed to an unidentified anharmonic resonance.
      Precise spectroscopic constants for the bands of each isotopic species are
      determined to allow future simulations for modeling atmospheric transmission and
      for remote sensing applications.

PMID- 9252293
TI  - IR-Microwave Double Resonance Studies of Tunneling Frequencies in the nu1 and nu3
      States of Ammonia
AB  - Infrared laser-microwave double resonance spectroscopy has been used to observe
      tunneling transitions in the nu1 and nu3 hydrogen stretching states of NH3 .
      Inversion frequencies in 15 rotational states of nu1 and 6 rotational states of
      nu3 were measured to accuracies of &plusmn;25 kHz. Comparisons between ground
      state and v 1 = 1 data indicate that x-y Coriolis interactions are responsible
      for much of the angular momentum dependence of the nu1 inversion splittings. The
      J ,K rotational quantum number dependence for tunneling in nu3 is very different
      from that in either the ground state or nu1 .

PMID- 9252294
TI  - Observation of Delta|k - l | = 3 Transitions in the nu3 Band of H3 O+
AB  - Although the vibration-rotation spectrum of H3 O+ has been studied extensively,
      there has been no experimental information on the value of the C rotational
      constant because of the absence of any observed Delta|k - l | not equal 0
      forbidden transitions. However, as pointed out by Verhoeve et al. in their far
      infrared spectroscopic work [P. Verhoeve, M. Versluis, J. J. Ter Meulen, W. L.
      Meerts, and A. Dynamus, Chem. Phys. Lett. 161, 195-201 (1989)], a near degeneracy
      exists between some (J , 0)+ and (J , 3)- ground state rotation-inversion levels,
      which causes sizable shifts in these levels due to off-diagonal centrifugal
      distortion. These shifts were observed in the ground state combination
      differences of the nu3 fundamental transitions. We have observed 11 forbidden
      Delta|k - l | = 3 transitions to the nu3 band induced by the mixing in the ground
      state and involving the J = 7, 9, and 11 levels, and determined the energy
      difference between different K levels, the C rotational constant, and the off
      diagonal centrifugal distortion mixing coefficient.

PMID- 9252295
TI  - Assignment of the Vibrations in the Near-Infrared Spectra of Phenol-OH(OD)
      Derivatives and Application to the Phenol-Pyrazine Complex
AB  - The near-infrared spectra (7200-3800 cm-1 ) of seven phenols OH-OD (4-CH3 , H, 4
      Cl, 4-Br, 3-Br, 3,4-diCl, 3-5-diCl) are investigated at room temperature in
      carbon tetrachloride. The mid-infrared spectra of some phenol-OD have also been
      studied. Beside the first overtone of the nu(OH) stretching vibration, six
      absorptions disappear upon deuteration. The absorptions are assigned to
      combinations involving the nu(OH) stretching mode and aromatic ring vibrations,
      the nu(C-O) mode, or the delta(OH) mode. The anharmonicity and coupling constants
      are discussed. The isotopic ratio of the nu(OH) stretching fundamentals, of their
      first overtone, and the ratio of the anharmonicity constants are very insensitive
      to the nature of the phenol. The stability constants of complexes between phenols
      and base can be computed from several near-infrared absorptions and this is
      illustrated for the 3,5-dichlorophenol-pyrazine complex.

PMID- 9252296
TI  - The CaCCH A 2 Pi- X ; 2 Sigma+ 52 2 and 52 0 Bands Studied by High Resolution
      Spectroscopy: The Ca-C-C Bending Vibration and Vibronic Interaction
AB  - The CaCCH 52 2 and 52 0 bands in the A 2 Pi- X ; 2 Sigma+ system, involving the
      excited Ca-C-C bending vibrations, have been rotationally analyzed via CW dye
      laser excitation and dispersed fluorescence with a CCD array detector. The A 2 Pi
      v 5 = 2 level is subject to Renner-Teller and spin-orbit splittings; in addition,
      K -resonance interactions are observed between the nearby 2 Phi and 2 Pi vibronic
      components. With a full matrix treatment of the six vibronic components (kappa2
      Pi, MU2 Pi, and 2 Phi) in the upper state, the line positions of the six subbands
      of the 52 2 band were fitted simultaneously by least squares. The three higher
      vibronic components, especially the kappa2 Pi1/2 component, were found to be
      perturbed strongly by the lower vibronic components of the v 5 = 3 level. This
      perturbation has been analyzed by means of second-order perturbation theory
      involving the B ; 2 Sigma+ electronic state and results in an estimate of the
      dipolar vibronic interaction parameter, epsilon5 (2) omega5 = -8.31 cm-1 . The 52
      0 band was studied through dispersed fluorescence and served to establish an
      accurate energy of the v 5 = 2 vibrational level relative to the zero-point
      vibration level in both the A and X ; states.

PMID- 9252297
TI  - Fourier Transform Emission Spectroscopy of ScH and ScD: The New Singlet
      Electronic States A 1 Delta, D 1 Pi, E 1 Delta, and F 1 Sigma-
AB  - The emission spectra of ScH and ScD have been investigated in the near infrared
      and visible using a Fourier transform spectrometer. The molecules were excited in
      a scandium hollow cathode lamp operated with neon gas and a trace of hydrogen or
      deuterium. Apart from the X 1 Sigma+ , B 1 Pi, C 1 Sigma+ , and G 1 Pi states
      reported previously [R. S. Ram and P. F. Bernath, J. Chem. Phys. 105, 2668-2674
      (1996)], four additional new singlet electronic states A 1 Delta, D 1 Pi, E 1
      Delta, and F 1 Sigma- have been identified below 21 000 cm-1 . The rotational
      analysis of several vibrational bands of the D 1 Pi-X 1 Sigma+ , D 1 Pi-A 1
      Delta, E 1 Delta-B 1 Pi, E 1 Delta-A 1 Delta, and F 1 Sigma- -B 1 Pi transitions
      has been carried out and spectroscopic constants have been determined. The E 1
      Delta state of ScH was not located because of the very weak intensity of the E 1
      Delta-B 1 Pi and E 1 Delta-A 1 Delta transitions.

PMID- 9252298
TI  - Vibrational Assignment and Anharmonic Resonance Analysis of the Dispersed
      Fluorescence and Stimulated Emission Pumping Spectra of DFCO (S 0 ) up to 9000 cm
      1
AB  - Dispersed fluorescence and stimulated emission pumping spectra of jet-cooled DFCO
      from the 2(1) 6(2) , 5(1) 6(4) , 2(1) 5(1) 6(2) , and 5(1) 6(6) vibrational
      states of S 1 are presented up to 9000 cm-1 . Progressions are assigned primarily
      to vibrational states with excitation in the Franck-Condon active modes nu2 , nu5
      , and nu6 . The spectrum is perturbed by a 266 (nu2 approximately 2nu6 ), a 233
      (nu2 approximately 2nu3 ), and a 3566 (nu3 + nu5 approximately 2nu6 ) anharmonic
      resonance. These three resonances are increasingly important at high vibrational
      energies, thus explaining the complexity of the DFCO spectrum compared to that of
      HFCO. Seventy-five vibrational states are assigned as eigenstates of a 266, 233,
      and 3566 anharmonic resonance Hamiltonian. The rms deviation in the calculated
      energies is 1.2 cm-1 . Harmonic frequencies and anharmonic constants are
      reported. These are compared to constants derived from ab initio potential energy
      surfaces.

PMID- 9252299
TI  - Permanent Dipole Moments of Methane-Type Molecules: Calculation of the DeltaJ = 0
      Matrix Elements in the l = 1 Vibrational State
AB  - We examined permanent dipole moments (PDMs) of methane-type molecules induced by
      molecular internal motions which are expanded in terms of the vibrational
      coordinate operator q , total angular momentum operator J , and vibrational
      angular momentum operator l . The qq -, JJ -, Jl -, and ll -type quadratic terms
      of these operators contribute to the production of PDMs. The DeltaJ = 0 matrix
      elements of the four PDMs are calculated for the first excited state of the
      triply degenerate vibrational mode; a portion are numerically given in a table
      for the J </= 6 levels. We have also compared them with the PDM represented by
      the rotational angular momentum operator R = J - l and discussed an application
      of the present calculations to the v 3 = 2 state of methane.

PMID- 9252300
TI  - Submillimeter-Wave Absorption Spectroscopy of the Ar-CO Complex: Detection of the
      van der Waals Bending Vibration
AB  - Van der Waals bending rovibrational transitions of the Ar-CO complex were
      observed between 308 and 383 GHz using submillimeter-wave absorption spectroscopy
      in a pulsed supersonic jet. The submillimeter radiation was generated by a phase
      stabilized backward wave oscillator source. Fourteen transitions of the P and R
      branch of the bending vibration were measured with an accuracy of about 100 kHz.
      The frequencies were fitted using effective molecular parameters including the
      band origin and the rotational constants for the ground state and for the excited
      bending vibrational state.

PMID- 9252301
TI  - The High-Resolution Spectrum of Water Vapor between 11 600 and 12 750 cm-1
AB  - The absorption spectrum of water vapor has been recorded between 11 600 and 12
      750 cm-1 with a Fourier transform spectrometer (Kitt Peak, Az) at a resolution of
      0.012 cm-1 and with a path length of 434 m. The line assignment has led to the
      determination of 506 accurate energy levels of the (310) (211), (112), (013),
      (230), (131), (032), and (051) vibrational states which belong to the so-called
      3nu + delta resonance polyad. The rotational energy levels obtained are on the
      average in agreement with those reported recently by R. Toth (J. Mol. Spectrosc.
      166, 176-183 (1994)) for the strong bands, but there are differences for high J
      levels or weak bands levels (about 15% of all levels). The experimental
      rotational energy levels have been fitted using Pade-Borel approximants and a set
      of 104 vibrational energies and rotational, resonance, and centrifugal distortion
      constants for the (310), (211), (112), (013), (230), (131), (032), and (051)
      vibrational states have been determined.

PMID- 9252302
TI  - High Resolution Study of the nu2 , 2nu1 , nu1 + nu3 , and 2nu3 Bands of Hydrogen
      Telluride: Determination of Equilibrium Rotational Constants and Structure
AB  - High resolution Fourier transform spectra of a natural and a 130 Te monoisotopic
      sample of H2 Te have been recorded at a resolution of 0.0022 cm-1 in the 11.6 MUm
      spectral region, as well as a spectrum of a natural sample of H2 Te at a
      resolution of 0.0051 cm-1 in the 2.4 MUm region. In the 11.6 MUm region the main
      absorbing band is the nu2 band, the analysis of which was rather easy. On the
      other hand, in the 2.4 MUm region three bands are absorbing, namely 2nu1 , nu1 +
      nu3 , and 2nu3 , the last being much weaker than the others. The analysis in this
      spectral domain was much more difficult because of resonances. Indeed it proved
      not possible to reproduce the observed lines without taking into account the
      Darling-Dennison interaction between the levels of the (200) and (002) states and
      the Coriolis interactions between the levels of (200) and (101) and between those
      of (101) and (002). Considering these interactions allowed us to calculate very
      satisfactorily all the experimental levels, and precise sets of vibrational
      energies and rotational and coupling constants were obtained for the seven most
      abundant H2 Te isotopic species, namely H2 130 Te, H2 128 Te, H2 126 Te, H2 125
      Te, H2 124 Te, H2 123 Te, and H2 122 Te. For the most abundant species, H2 130
      Te, the band centers in cm-1 are nu0 (nu2 ) = 860.6563, nu0 (2nu1 ) = 4062.8842,
      nu0 (nu1 + nu3 ) = 4063.3697, and nu0 (2nu3 ) = 4137.0454. These results,
      combined with those obtained for other vibrational states, have been used to
      derive the equilibrium rotational constants and their corrections. Finally, by
      neglecting the electronic corrections, the equilibrium structure of H2 130 Te was
      obtained as follows: r e (Te-H) = 1.65145(10) A, alphae (HTeH) =
      90.2635(90)degrees.

PMID- 9252303
TI  - Raman Spectroscopic Studies on SOF2 in Argon Matrices
AB  - The vibrational fine structure of SOF2 has been studied in the solid state (80 K,
      15 K) and in argon matrices (M /S = 30, 100, 250, 500, 1000) by Raman
      spectroscopy. The splitting of the vibrations at the solid state and in low
      diluted argon matrices reflect the interactions between the SOF2 molecules. The
      influence of annealing procedures at different dilution ratios with respect to
      the formation of van der Waals oligomers is discussed.

PMID- 9252304
TI  - Mid-Infrared Diode Laser Spectroscopy of X ; 1 A ' HC35 Cl
AB  - The observation of the C-Cl stretching fundamental of HC35 Cl in its ground X ; 1
      A ' state is reported. HCCl was formed in a continuous flow system by the excimer
      laser photolysis of CHBr2 Cl at 193 nm and the transient absorption recorded by
      infrared diode laser spectroscopy. The band has a -type character and the
      fundamental vibrational frequency is found to be 811.5963 cm-1 . No evidence was
      found for perturbations in either the ground or vibrationally excited states,
      implying that the excited triplet a 3 A " states lies above the C-Cl stretching
      level in HCCl. The observed rotation-vibration transitions were well fit by a
      standard asymmetric rotor Hamiltonian. There is a decrease in the A rotational
      constant on vibrational excitation, suggesting that some bend-C-Cl stretch
      coupling is present.

PMID- 9252305
TI  - Laser Excitation Spectroscopy of the A 3 Piu -X ; 3 Sigmag - Transition of the
      NCN Radical
AB  - The (010)-(010) band of the A 3 Piu -X ; 3 Sigmag - transition of the NCN radical
      at 328 nm has been reexamined at Doppler-limited resolution by laser excitation
      spectroscopy. The molecule was generated in a microwave discharge through N2 and
      CF4 in helium. Both the 3 Deltag -3 Piu and the 3 Sigmag +/- -3 Piu vibronic
      components of the transition have been observed and rotationally analyzed. The
      Renner-Teller parameter, varepsilonomega2 , for NCN in the excited A 3 Piu state
      is determined to be -91.1213(16) cm-1 . Estimates for the ground and excited
      state bending vibrational wavenumbers of 437.7(14) and 533.95(70) cm-1
      respectively have been obtained.

PMID- 9252306
TI  - Fourier Transform Infrared Emission Spectroscopy of NaCl and KCl
AB  - The infrared emission spectra of NaCl and KCl have been recorded at high
      resolution with a Fourier transform spectrometer. A total of 929 lines belonging
      to 8 vibrational bands, 1-0 to 8-7, for Na35 Cl, 252 lines of 1-0, 2-1, and 3-2
      bands of Na37 Cl, and 355 lines of 1-0, 2-1, 3-2, and 4-3 bands of K35 Cl have
      been measured and combined with the existing microwave and millimeter-wave data
      to obtain a set of refined molecular constants. The data for Na35 Cl and Na37 Cl
      have also been fitted to determine the Dunham Yij constants and mass-reduced
      Dunham constants Uij . In one fit all Uij 's were treated as adjustable
      parameters while in a second fit only Ui 0 's and Ui 1 's were allowed to vary
      freely with the remaining Uij constants determined by the constraints imposed by
      the Dunham model. In addition, the internuclear potential energy parameters were
      determined by fitting the entire NaCl data set to the eigenvalues of the
      Schrodinger equation containing a parameterized potential energy function.

PMID- 9252307
TI  - The Inversion-Torsion Potential Function for Hydrazine
AB  - The torsion-inversion potential surface for hydrazine has been determined from
      the rovibrational data using a new rotation-torsion-inversion Hamiltonian. All
      elements of the inverse moment of inertia tensor have been expanded into mixed
      Fourier series of large amplitude coordinates. That gives two major advantages:
      (i) no numerical integration is necessary at any step of calculation, and (ii)
      the three-dimensional integrals have been replaced by the products of one
      dimensional integrals. It has been proven that the inversion-torsion coupling in
      hydrazine is negligible and the inversion-inversion coupling is very strong. The
      barrier to inversion of 2072 cm-1 is slightly higher than that in ammonia and the
      barrier to internal rotation of 934 cm-1 is relatively high but lower than that
      determined previously from one-dimensional models.

PMID- 9252308
TI  - High Resolution Infrared Spectrum of the C-F Stretching Mode of CH2 F37 Cl
AB  - Diode laser spectra of CH2 F37 Cl (95% isotopically pure sample) have been
      recorded in the 9.4 MUm region characterized by the nu4 fundamental. The spectral
      analysis allowed the assignment of more than 3700 transitions with J </= 92 and
      Ka </= 16 of the expected a /b -hybrid structure. The nu4 fundamental, whose
      origin is at 1067.7140 cm-1 , mainly interacts through a - and b -type Coriolis
      coupling with the nu9 fundamental located at lower wavenumbers near 1002 cm-1 .
      Local effects arising from Fermi resonance with nu5 + nu6 have been observed for
      the K a ' = 14 level. An effective set of upper state molecular constants was
      determined by fitting the less perturbed transitions to the Watson's A-reduction
      Hamiltonian in the Ir representation. Due to the second-order a -type Coriolis
      resonance, a number of perturbation-allowed transitions of nu9 were observed and
      assigned near the avoided crossing. Using a suitable program, we experienced a
      two band system analysis which produced the molecular constants of the v 4 = 1
      and v 9 = 1 states along with the interaction parameter. From spectral simulation
      of nu4 , the |DeltaMUa /DeltaMUb | dipole moment ratio was estimated to be 1.8 +/
      0.2.

PMID- 9252309
TI  - The Effects of Nonzero Total Electron Spin in the X ; 3 B 1 State of Methylene
      CH2
AB  - We report here how we have incorporated the effects of a nonzero total electron
      spin in the MORBID Hamiltonian and computer program [P. Jensen, J. Mol.
      Spectrosc. 128, 478-501 (1988); J. Chem. Soc. Faraday Trans. 2 84, 1315-1340
      (1988); in "Methods in Computational Molecular Physics" (S. Wilson and G. H. F.
      Diercksen, Eds.), Plenum Press, New York, 1992] for calculating the rovibronic
      energies of a triatomic molecule directly from the potential energy function. The
      spin-spin and spin-rotation Hamiltonian terms, given in a form depending on the
      vibrational coordinates, have been expressed in terms of isotope-independent
      functions and added to the MORBID rotation-vibration Hamiltonian. The eigenvalues
      of the resulting Hamiltonian are obtained in a variational procedure. This method
      is tested on the methylene radical CH2 in the X ; 3 B 1 electronic ground state
      for which we describe simultaneously the splittings due to electron spin for the
      isotopomers 12 CH2 , 12 CD2 , and 13 CH2 . For these molecules, experimental data
      are available, and we compare the results of least-squares fits to these data
      with predictions from ab initio theory.

PMID- 9252310
TI  - Infrared Analysis of the Anharmonic Resonance between nu8 + nu9 and the Dark
      State nu6 + nu7 of HNO3
AB  - The high-resolution FTIR spectrum of the nu8 + nu9 band of HNO3 around 1205 cm-1
      has been measured and analyzed. The bright state was found to be strongly
      perturbed by its neighboring dark state nu6 + nu7 at the coincident levels.
      Taking account of the DeltaK = &plusmn;2 anharmonic resonance, a simultaneous fit
      of nu8 + nu9 and nu6 + nu7 was performed leading to a good reproduction of the
      nu8 + nu9 band with a rms uncertainty of 0.00046 cm-1 . A set of rovibrational
      constants for nu8 + nu9 were accurately determined, while for nu6 + nu7 the
      rotational constant B and the band origin were obtained.

PMID- 9252311
TI  - Interpretation of the Relative Intensities of the (4000), (3100), and (5000)
      Local-Mode Vibrational Bands of Germane

PMID- 9252312
TI  - A Note on the Spectroscopic Constants of NF3

PMID- 9252313
TI  - Improved Molecular Constants for the Ground State of HO2

PMID- 9252314
TI  - On the Electronic Structure of FeF and Its Cations

PMID- 9252316
TI  - Neighborhoods and violent crime: a multilevel study of collective efficacy.
AB  - It is hypothesized that collective efficacy, defined as social cohesion among
      neighbors combined with their willingness to intervene on behalf of the common
      good, is linked to reduced violence. This hypothesis was tested on a 1995 survey
      of 8782 residents of 343 neighborhoods in Chicago, Illinois. Multilevel analyses
      showed that a measure of collective efficacy yields a high between-neighborhood
      reliability and is negatively associated with variations in violence, when
      individual-level characteristics, measurement error, and prior violence are
      controlled. Associations of concentrated disadvantage and residential instability
      with violence are largely mediated by collective efficacy.

PMID- 9252321
TI  - Asymmetric catalysis with water: efficient kinetic resolution of terminal
      epoxides by means of catalytic hydrolysis.
AB  - Epoxides are versatile building blocks for organic synthesis. However, terminal
      epoxides are arguably the most important subclass of these compounds, and no
      general and practical method exists for their production in enantiomerically pure
      form. Terminal epoxides are available very inexpensively as racemic mixtures, and
      kinetic resolution is an attractive strategy for the production of optically
      active epoxides, given an economical and operationally simple method. Readily
      accessible synthetic catalysts (chiral cobalt-based salen complexes) have been
      used for the efficient asymmetric hydrolysis of terminal epoxides. This process
      uses water as the only reagent, no added solvent, and low loadings of a
      recyclable catalyst (<0.5 mole percent), and it affords highly valuable terminal
      epoxides and 1, 2-diols in high yield with high enantiomeric enrichment.

PMID- 9252322
TI  - Protein transport by purified yeast Sec complex and Kar2p without membranes.
AB  - Posttranslational protein translocation across the endoplasmic reticulum membrane
      of yeast requires a seven-component transmembrane complex (the Sec complex) in
      collaboration with the lumenal Kar2 protein (Kar2p). A translocation substrate
      was initially bound to the cytosolic face of the purified Sec complex in a signal
      sequence-dependent but Kar2p- and nucleotide-independent manner. In a subsequent
      reaction, in which Kar2p interacted with the lumenal face of the Sec complex and
      hydrolyzed adenosine triphosphate, the substrate moved through a channel formed
      by the Sec complex and was released at the lumenal end. Movement through the
      channel occurred in detergent solution in the absence of a lipid bilayer.

PMID- 9252323
TI  - daf-2, an insulin receptor-like gene that regulates longevity and diapause in
      Caenorhabditis elegans.
AB  - A C. elegans neurosecretory signaling system regulates whether animals enter the
      reproductive life cycle or arrest development at the long-lived dauer diapause
      stage. daf-2, a key gene in the genetic pathway that mediates this endocrine
      signaling, encodes an insulin receptor family member. Decreases in DAF-2
      signaling induce metabolic and developmental changes, as in mammalian metabolic
      control by the insulin receptor. Decreased DAF-2 signaling also causes an
      increase in life-span. Life-span regulation by insulin-like metabolic control is
      analogous to mammalian longevity enhancement induced by caloric restriction,
      suggesting a general link between metabolism, diapause, and longevity.

PMID- 9252325
TI  - Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that
      transport bacteria.
AB  - The epithelium that lines the gut is impermeable to macromolecules and
      microorganisms, except in Peyer's patches (PPs), where the lymphoid follicle
      associated epithelium (FAE) contains M cells that transport antigens and
      microorganisms. A cultured system that reproduces the main characteristics of FAE
      and M cells was established by cultivation of PP lymphocytes with the
      differentiated human intestinal cell line Caco-2. Lymphocytes settled into the
      epithelial monolayer, inducing reorganization of the brush border and a
      temperature-dependent transport of particles and Vibrio cholerae. This model
      system could prove useful for intestinal physiology, vaccine research, and drug
      delivery studies.

PMID- 9252326
TI  - Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after
      long-term administration of phencyclidine.
AB  - The effects of the psychotomimetic drug phencyclidine on the neurochemistry and
      function of the prefrontal cortex in vervet monkeys were investigated. Monkeys
      treated with phencyclidine twice a day for 14 days displayed performance deficits
      on a task that was sensitive to prefrontal cortex function; the deficits were
      ameliorated by the atypical antipsychotic drug clozapine. Repeated exposure to
      phencyclidine caused a reduction in both basal and evoked dopamine utilization in
      the dorsolateral prefrontal cortex, a brain region that has long been associated
      with cognitive function. Behavioral deficits and decreased dopamine utilization
      remained after phencyclidine treatment was stopped, an indication that these
      effects were not simply due to direct drug effects. The data suggest that
      repeated administration of phencyclidine in monkeys may be useful for studying
      psychiatric disorders associated with cognitive dysfunction and dopamine
      hypofunction in the prefrontal cortex, particularly schizophrenia.

PMID- 9252327
TI  - Telomerase catalytic subunit homologs from fission yeast and human.
AB  - Catalytic protein subunits of telomerase from the ciliate Euplotes aediculatus
      and the yeast Saccharomyces cerevisiae contain reverse transcriptase motifs. Here
      the homologous genes from the fission yeast Schizosaccharomyces pombe and human
      are identified. Disruption of the S. pombe gene resulted in telomere shortening
      and senescence, and expression of mRNA from the human gene correlated with
      telomerase activity in cell lines. Sequence comparisons placed the telomerase
      proteins in the reverse transcriptase family but revealed hallmarks that
      distinguish them from retroviral and retrotransposon relatives. Thus, the
      proposed telomerase catalytic subunits are phylogenetically conserved and
      represent a deep branch in the evolution of reverse transcriptases.

PMID- 9252328
TI  - Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and
      disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter
      AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San
      Francisco City Cohort (SFCC), ALIVE Study.
AB  - The critical role of chemokine receptors (CCR5 and CXCR4) in human
      immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a
      search for polymorphisms in other chemokine receptor genes that mediate HIV-1
      disease progression. A mutation (CCR2-64I) within the first transmembrane region
      of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an
      allele frequency of 10 to 15 percent among Caucasians and African Americans.
      Genetic association analysis of five acquired immunodeficiency syndrome (AIDS)
      cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on
      the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2
      64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for
      the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing
      chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays
      AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS
      patients whose disease progresses rapidly (less than 3 years until onset of AIDS
      symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+
      genotype, whereas the survival of 28 to 29 percent of long-term survivors, who
      avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2
      or CCR5.

PMID- 9252329
TI  - AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.
AB  - Members of the recently recognized SRC-1 family of transcriptional coactivators
      interact with steroid hormone receptors to enhance ligand-dependent
      transcription. AIB1, a member of the SRC-1 family, was cloned during a search on
      the long arm of chromosome 20 for genes whose expression and copy number were
      elevated in human breast cancers. AIB1 amplification and overexpression were
      observed in four of five estrogen receptor-positive breast and ovarian cancer
      cell lines. Subsequent evaluation of 105 unselected specimens of primary breast
      cancer found AIB1 amplification in approximately 10 percent and high expression
      in 64 percent of the primary tumors analyzed. AIB1 protein interacted with
      estrogen receptors in a ligand-dependent fashion, and transfection of AIB1
      resulted in enhancement of estrogen-dependent transcription. These observations
      identify AIB1 as a nuclear receptor coactivator whose altered expression may
      contribute to development of steroid-dependent cancers.

PMID- 9252330
TI  - Pain affect encoded in human anterior cingulate but not somatosensory cortex.
AB  - Recent evidence demonstrating multiple regions of human cerebral cortex activated
      by pain has prompted speculation about their individual contributions to this
      complex experience. To differentiate cortical areas involved in pain affect,
      hypnotic suggestions were used to alter selectively the unpleasantness of noxious
      stimuli, without changing the perceived intensity. Positron emission tomography
      revealed significant changes in pain-evoked activity within anterior cingulate
      cortex, consistent with the encoding of perceived unpleasantness, whereas primary
      somatosensory cortex activation was unaltered. These findings provide direct
      experimental evidence in humans linking frontal-lobe limbic activity with pain
      affect, as originally suggested by early clinical lesion studies.

PMID- 9252331
TI  - Protein oxidation in aging, disease, and oxidative stress.

PMID- 9252332
TI  - Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis.
AB  - Protein kinase C theta (PKCtheta) is a member of the novel or nPKC family. A
      functional role for PKCtheta is unknown. The present studies demonstrate that
      PKCtheta is cleaved in the third variable region (V3) in apoptosis induced by
      diverse agents. PKCtheta cleavage is blocked in cells that overexpress the anti
      apoptotic Bcl-xL or the baculovirus p35 protein. PKCtheta is cleaved by Caspase-3
      and by apoptotic cell lysates at a DEVD354/K site. We also show that
      overexpression of the cleaved kinase-active PKCtheta fragment, but not full
      length PKCtheta or a kinase-inactive fragment, results in induction of sub-G1
      phase DNA, nuclear fragmentation, and lethality. These findings indicate that
      proteolytic cleavage of PKCtheta by Caspase-3 induces events characteristic of
      apoptosis.

PMID- 9252333
TI  - Gpa2p, a G-protein alpha-subunit, regulates growth and pseudohyphal development
      in Saccharomyces cerevisiae via a cAMP-dependent mechanism.
AB  - The small GTP-binding protein Ras and heterotrimeric G-proteins are key
      regulators of growth and development in eukaryotic cells. In mammalian cells, Ras
      functions to regulate the mitogen-activated protein kinase pathway in response to
      growth factors, whereas many heterotrimeric GTP-binding protein alpha-subunits
      modulate cAMP levels through adenylyl cyclase as a consequence of hormonal
      action. In contrast, in the yeast Saccharomyces cerevisiae, it is the Ras1 and
      Ras2 proteins that regulate adenylyl cyclase. Of the two yeast G-protein alpha
      subunits (GPA1 and GPA2), only GPA1 has been well studied and shown to negatively
      regulate the mitogen-activated protein kinase pathway upon pheromone stimulation.
      In this report, we show that deletion of the GPA2 gene encoding the other yeast G
      protein alpha-subunit leads to a defect in pseudohyphal development. Also, the
      GPA2 gene is indispensable for normal growth in the absence of Ras2p. Both of
      these phenotypes can be rescued by deletion of the PDE2 gene product, which
      inactivates cAMP by cleavage, suggesting that these phenotypes can be attributed
      to low levels of intracellular cAMP. In support of this notion, addition of
      exogenous cAMP to the growth media was also sufficient to rescue the phenotype of
      a GPA2 deletion strain. Taken together, our results directly demonstrate that a G
      protein alpha-subunit can regulate the growth and pseudohyphal development of S.
      cerevisiae via a cAMP-dependent mechanism. Heterologous expression of mammalian G
      protein alpha-subunits in these yeast GPA2 deletion strains could provide a
      valuable tool for the mutational analysis of mammalian G-protein function in an
      in vivo null setting.

PMID- 9252334
TI  - Five transmembrane helices form the sugar pathway through the Na+/glucose
      cotransporter.
AB  - To test the hypothesis that the C-terminal half of the Na+/glucose cotransporter
      (SGLT1) contains the sugar permeation pathway, a cDNA construct (C5) coding for
      rabbit SGLT1 amino acids 407-662, helices 10-14, was expressed in Xenopus
      oocytes. Expression and function of C5 was followed by Western blotting, electron
      microscopy, radioactive tracer, and electrophysiological methods. The C5 protein
      was synthesized in 20-fold higher levels than SGLT1. The particle density in the
      protoplasmic face of the oocyte plasma membrane increased 2-fold after C5-cRNA
      injection compared with noninjected oocytes. The diameters of the C5 particles
      were heterogeneous (4.8 +/- 0.3, 7.1 +/- 1.2, and 10.3 +/- 0.8 nm) in contrast to
      the endogenous particles (7.6 +/- 1.2 nm). C5 increased the alpha-methyl-D
      glucopyranoside (alphaMDG) uptake up to 20-fold above that of noninjected oocytes
      and showed an apparent K0.5alphaMDG of 50 mM and a turnover of approximately 660
      s-1. Influx was independent of Na+ with transport characteristics similar to
      those of SGLT1 in the absence of Na+: 1) selective (alphaMDG > D-glucose > D
      galactose >> L-glucose approximately D-mannose), 2) inhibited by phloretin, KiPT
      = approximately 500 microM, and 3) insensitive to phlorizin. These results
      indicate that C5 behaves as a specific low affinity glucose uniporter.
      Preliminary studies with three additional constructs, hC5 (the human equivalent
      of C5), hC4 (human SGLT1 amino acids 407-648, helices 10-13), and hN13 (amino
      acids 1-648, helices 1-13), further suggest that helices 10-13 form the sugar
      permeation pathway for SGLT1.

PMID- 9252335
TI  - Nuclear targeting of chlorin e6 enhances its photosensitizing activity.
AB  - Although photosensitizers, molecules that produce active oxygen species upon
      activation by visible light, are being extensively used in photodynamic therapy
      to treat cancer and other clinical conditions, problems include normal cell and
      tissue damage and associated side effects, which are attributable in part to the
      fact that cytotoxic effects are largely restricted to the plasma membrane. We
      have previously shown that the photosensitizer chlorin e6 has significantly
      higher photosensitizing activity when present in conjugates containing specific
      ligands and thus able to be internalized by receptor-expressing cells. In this
      study we use insulin-containing conjugates to which variants of the simian virus
      SV40 large tumor antigen nuclear localization signal (NLS) were linked to target
      chlorin e6 to the nucleus, a hypersensitive site for active oxygen species
      induced damage. NLSs were either included as peptides cross-linked to the carrier
      bovine serum albumin or encoded within the sequence of a beta-galactosidase
      fusion protein carrier. The results for photosensitization demonstrate clearly
      for the first time that NLSs increase the photosensitizing activity of chlorin
      e6, maximally reducing the EC50 by a factor of over 2000-fold. This has wide
      reaching implications for achieving efficient cell type-specific photodynamic
      therapy.

PMID- 9252336
TI  - The actin cytoskeleton is required for receptor-mediated endocytosis in mammalian
      cells.
AB  - Actin filament organization is essential for endocytosis in yeast. In contrast,
      the actin-depolymerizing agent cytochalasin D has yielded ambiguous results as to
      a role for actin in receptor-mediated endocytosis in mammalian cells. We have
      therefore re-examined this issue using highly specific reagents known to
      sequester actin monomers. Two of these reagents, thymosin beta4 and DNase I,
      potently inhibited the sequestration of transferrin receptors into coated pits as
      measured in a cell-free system using perforated A431 cells. At low
      concentrations, thymosin beta4 but not DNase I was stimulatory. Importantly, the
      effects of both reagents were specifically neutralized by the addition of actin
      monomers. A role for the actin cytoskeleton was also detected in intact cells
      where latrunculin A, a drug that sequesters actin monomers, inhibited receptor
      mediated endocytosis. Biochemical and morphological analyses suggest that these
      reagents inhibit later events in coated vesicle budding. These results provide
      new evidence that the actin cytoskeleton is required for receptor-mediated
      endocytosis in mammalian cells.

PMID- 9252337
TI  - New beta-hydroxyaspartate derivatives are competitive blockers for the bovine
      glutamate/aspartate transporter.
AB  - Four subtypes of excitatory amino acid transporters (EAAT1-4) have been
      identified in the mammalian brain. A number of pharmacological agents have been
      developed to study their intrinsic properties and function. Up to now, blockers
      were available only for EAAT2, whereas all the inhibitors of glutamate uptake
      active on the other subtypes were proved to be substrates of the transporters. We
      synthesized five new derivatives of DL-threo-beta-hydroxyaspartic acid, a well
      known general substrate of EAATs, and investigated their potential blocking
      activity on the cloned bovine EAAT1 expressed in the Xenopus oocyte system, by
      using radiotracer and voltage-clamp techniques. Two of our derivatives proved to
      be substrates for bovine EAAT1, with reduced electrogenicity compared with their
      parent compound, and an affinity of 40 and 64 microM. The last three derivatives
      displayed a blocking activity on bovine EAAT1. The affinity of DL-threo-beta
      benzoyloxyaspartate and DL-threo-beta-(1-naphthoyl)oxyaspartate was determined by
      Schild analysis as 17.2 and 52.1 microM, respectively. These blockers should help
      in the better understanding of the key intrinsic properties of EAAT1. Moreover,
      they appear as good candidates for a general blocking activity on EAATs.

PMID- 9252338
TI  - An EPR investigation of the products of the reaction of cytosolic and
      mitochondrial aconitases with nitric oxide.
AB  - Cellular studies have indicated that some Fe-S proteins, and the aconitases in
      particular, are targets for nitric oxide. Specifically, NO has been implicated in
      the intracellular process of the conversion of active cytosolic aconitase
      containing a [4Fe-4S] cluster, to its apo-form which functions as an iron
      regulatory protein. We have undertaken the in vitro study of the reaction of NO
      with purified forms of both mitochondrial and cytosolic aconitases by following
      enzyme activity and by observing the formation of EPR signals not shown by the
      original reactants. Inactivation by either NO solutions or NO-producing NONOates
      under anaerobic conditions is seen for both enzyme isoforms. This inactivation,
      which occurs in the presence or absence of substrate, is accompanied by the
      appearance of the g = 2.02 signals of the [3Fe-4S] clusters and the g
      approximately 2.04 signal of a protein-bound dinitrosyl-iron-dithiol complex in
      the d7 state. In addition, in the reaction of cytosolic aconitase, the transient
      formation of a thiyl radical, g parallel = 2.11 and g perpendicular = 2.03, is
      observed. Disassembly of the [3Fe-4S] clusters of the inactive forms of the
      enzymes upon the anaerobic addition of NO is also accompanied by the formation of
      the g approximately 2.04 species and in the case of mitochondrial aconitase, a
      transient signal at g approximately 2. 032 appeared. This signal is tentatively
      assigned to the d9 form of an iron-nitrosyl-histidyl complex of the mitochondrial
      protein. Inactivation of the [4Fe-4S] forms of both aconitases by either
      superoxide anion or peroxynitrite produces the g = 2.02 [3Fe-4S] proteins.

PMID- 9252339
TI  - The D1 C-terminal processing protease of photosystem II from Scenedesmus
      obliquus. Protein purification and gene characterization in wild type and
      processing mutants.
AB  - Polypeptide D1 of the photosystem II reaction center of oxygenic photosynthesis
      is expressed in precursor form (pre-D1), and it must be proteolytically processed
      at its C terminus to enable assembly of the manganese cluster responsible for
      photosynthetic water oxidation. A rapid and highly sensitive enzyme-linked
      immunosorbent assay-based microtiter plate method is described for assaying this
      D1 C-terminal processing protease. A protocol is described for the isolation and
      purification to homogeneity of the enzyme from the green alga, Scenedesmus
      obliquus. Amino acid sequence information on the purified protease was used to
      clone the corresponding gene, the translated sequence of which is presented. A
      comparison of the gene product with homologous proteases points to a region of
      conserved residues that likely corresponds to the active site of a new class of
      serine protease. The LF-1 mutant strain of Scenedesmus (isolated by Dr. Norman
      Bishop) is incapable of processing pre-D1. We show here that the C-terminal
      processing protease gene in this strain contains a single base deletion that
      causes a frame shift and a premature stop of translation within the likely active
      site of the enzyme. A suppressor strain, LF-1-RVT-1, which is photoautotrophic
      and capable of processing pre-D1 has a nearby single base insertion that restores
      the expression of active enzyme. These observations provide the first definitive
      proof that the enzyme isolated is responsible for in vivo proteolytic processing
      of pre-D1 and that no other protease can compensate for its loss.

PMID- 9252340
TI  - Alterations in the Chlamydomonas plastocyanin transit peptide have distinct
      effects on in vitro import and in vivo protein accumulation.
AB  - Nucleus-encoded chloroplast proteins that reside in the thylakoid lumen are
      synthesized as precursors with bipartite transit peptides that contain
      information for uptake and intra-chloroplast localization. We have begun to apply
      the superb molecular and genetic attributes of Chlamydomonas to study chloroplast
      protein import by creating a series of deletions in the transit peptide of
      plastocyanin and determining their effects on translocation into isolated
      Chlamydomonas chloroplasts. Most N-terminal mutations dramatically inhibited in
      vitro import, whereas replacement with a transit peptide from the gamma-subunit
      of chloroplast ATPase restored uptake. Thus, the N-terminal region has stroma
      targeting function. Deletions within the C-terminal portion of the transit
      peptide resulted in the appearance of import intermediates, suggesting that this
      region is required for lumen translocation and processing. Thus, despite its
      short length and predicted structural differences, the Chlamydomonas plastocyanin
      transit peptide has functional domains similar to those of vascular plants.
      Similar mutations have been analyzed in vivo by transforming altered genes into a
      mutant defective at the plastocyanin locus (K. L. Kindle, manuscript in
      preparation). Most mutations affected in vitro import more severely than
      plastocyanin accumulation in vivo. One exception was a deletion that removed
      residues 2-8, which nearly eliminated in vivo accumulation but had a modest
      effect in vitro. We suggest that this mutant precursor may not compete
      successfully with other proteins for the translocation pathway in vivo.
      Apparently, in vivo and in vitro analyses reveal different aspects of chloroplast
      protein biogenesis.

PMID- 9252341
TI  - Selection of carbonic anhydrase variants displayed on phage. Aromatic residues in
      zinc binding site enhance metal affinity and equilibration kinetics.
AB  - In all metalloenzymes, hydrophobic residues surround the metal binding site. In
      carbonic anhydrase II (CAII) residues Phe93, Phe95, and Trp97 flank two of the
      three histidines that coordinate zinc to form a hydrophobic cluster beneath the
      zinc binding site. A library of CAII variants differing in these hydrophobic
      amino acids was prepared using cassette mutagenesis, then displayed on
      filamentous phage, and screened for proteins retaining high zinc affinity. Wild
      type CAII was enriched 20-fold by selection, and consensus residues at each
      position were identified from the enriched CAII variants (Ile, Phe, Leu, and Met
      at position 93; Ile, Leu, and Met at position 95; and Trp and Val at position
      97). Highly selected variants have zinc affinity and catalytic activity nearly
      equal to that of wild-type CAII, indicating that the aromatic residues are not
      absolutely essential. However, the zinc dissociation rate constant and catalytic
      activity of the variants correlate with the volume of the amino acids at
      positions 93, 95, and 97. In summary, metalloenzyme variants displayed on phage
      can be selected on the basis of metal affinity; such methods will be useful for
      optimization of metal ion biosensors.

PMID- 9252342
TI  - Inflammatory activation of arachidonic acid signaling in murine P388D1
      macrophages via sphingomyelin synthesis.
AB  - Ceramide has emerged as an important lipid messenger for many cellular processes
      triggered via surface receptors. In the present study, inflammatory activation of
      P388D1 macrophages with bacterial lipopolysaccharide (LPS) and platelet
      activating factor (PAF) stimulated a transient accumulation of ceramide.
      Moreover, cell-permeable ceramide mimicked LPS/PAF in triggering arachidonate
      mobilization in these cells. LPS/PAF-induced ceramide synthesis did not result
      from sphingomyelinase activation but from increased de novo synthesis.
      Participation of this pathway in arachidonate signaling was detected since
      fumonisin B1, an inhibitor of de novo ceramide synthesis, was able to inhibit the
      LPS/PAF-induced response. These studies have uncovered a new role for
      sphingolipid metabolism in cellular signaling and constitute evidence that
      products of the sphingomyelin biosynthetic pathway may serve a specific role in
      signal transduction by influencing the activity of the novel Group V secretory
      phospholipase A2.

PMID- 9252343
TI  - Structural determinants of nicotinic acid adenine dinucleotide phosphate
      important for its calcium-mobilizing activity.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ through a
      mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. The
      structural determinants important for its Ca2+ release activity were investigated
      using a series of analogs. It is shown that changing the 3-carboxyl group of the
      nicotinic acid (NA) moiety in NAADP to either an uncharged carbinol or from the 3
      position to the 4-position of the pyridine ring totally eliminates the Ca2+
      release activity. Conversion of the 3-carboxyl to other negatively charged
      groups, either 3-sulfonate, 3-acetate, or 3-quinoline carboxylate, retains the
      Ca2+ release activity, although their half-maximal effective concentrations
      (EC50) are 100-200-fold higher. Changing the 6-amino group of the adenine to a
      hydroxyl group results in more than a 1000-fold decrease in the Ca2+ release
      activity. Conversion of the 2'-phosphate to 2',3'-cyclic phosphate or 3'
      phosphate likewise increases the EC50 by about 5- and 20-fold, respectively.
      Similar to NAADP, all of the active analogs can also desensitize the Ca2+ release
      mechanism at subthreshold concentrations, suggesting that this novel property is
      intrinsic to the release mechanism. The series of analogs used was produced by
      using ADP-ribosyl cyclase to catalyze the exchange of the nicotinamide group of
      various analogs of NADP with various analogs of NA. An important determinant in
      NA that is crucial to the base exchange reaction was shown to be the 2-position
      of the pyridine ring. Neither pyridine-2-carboxylate nor 2-methyl-NA support the
      exchange reaction. The negative charge and the position of the 3-carboxyl group
      are nonessential since both pyridine-3-carbinol and pyridine-4-carboxylate
      support the base exchange reaction. In addition to the information on the
      structure-activity relationships of NAADP and NA, this study also demonstrates
      the utility of the base exchange reaction as a general approach for synthesizing
      NAADP analogs.

PMID- 9252344
TI  - Characterization of RAC3, a novel member of the Rho family.
AB  - The small GTP-binding proteins Rac1 and Rac2 are critically important in
      regulating multiple signal transduction pathways in eukaryotic cells. Here we
      report the isolation of a novel third Rac family member, Rac3. Rac3 differs from
      Rac1/2 at its carboxyl-terminal end, a domain associated with subcellular
      localization and binding to specific cellular regulators. RAC3 mRNA expression
      patterns differ from those of RAC2, which is hematopoietic specific and also from
      those of RAC1. The RAC3 gene was mapped to chromosome 17q23-25, a region
      frequently deleted in breast cancer. Rac3 protein levels are not affected by
      organization of the actin cytoskeleton but remarkably, are serum-inducible. Rac3
      is an active GTPase, and this activity is regulated by Bcr. When constitutively
      activated, Rac3 is able to stimulate efficiently the c-Jun amino-terminal kinase
      signaling pathway. These findings support a role for Rac3 in intracellular
      signaling.

PMID- 9252345
TI  - c-Src is required for oxidative stress-mediated activation of big mitogen
      activated protein kinase 1.
AB  - Big mitogen-activated kinase 1 (BMK1) or extracellular signal-regulated kinase-5
      (ERK5) has recently been identified as a new member of the mitogen-activated
      protein kinase family. We have shown that BMK1 is activated to a greater extent
      by H2O2 than growth factors, suggesting that in comparison with other mitogen
      activated protein kinase family members, BMK1 is a redox-sensitive kinase.
      Previous investigations indicate that the tyrosine kinase c-Src mediates signal
      transduction by reactive oxygen species, including H2O2. Therefore, the role of
      Src kinase family members (c-Src and Fyn) in activation of the BMK1 by H2O2 in
      mouse fibroblasts was studied. An essential role for c-Src was suggested by four
      experiments. First, H2O2 stimulated c-Src activity rapidly in fibroblasts (peak
      at 5 min), which preceded peak activity of BMK1 (20 min). Second, specific Src
      family tyrosine kinase inhibitors (herbimycin A and CP-118,556) blocked BMK1
      activation by H2O2 in a concentration-dependent manner. Third, BMK1 activation in
      the response to H2O2 was completely inhibited in cells derived from mice
      deficient in c-Src, but not Fyn. Finally, BMK1 activity was much greater in v-Src
      transformed NIH-3T3 cells than wild type cells. These results demonstrate an
      essential role for c-Src in H2O2-mediated activation of BMK1 and suggest that
      redox-sensitive regulation of BMK1 is a new function for c-Src.

PMID- 9252346
TI  - A cell binding domain from the alpha3 chain of type IV collagen inhibits
      proliferation of melanoma cells.
AB  - Our previous studies have shown that a peptide corresponding to the residue
      sequence 185-203 of the NC1 domain of the alpha3 chain of basement membrane
      collagen (type IV) inhibits the activation of polymorphonuclear leukocytes.
      Peptides from the same region of the alpha1, alpha2, alpha4, and alpha5(IV)
      chains did not exhibit this property. Because of the intimate relationship
      between metastasizing neoplastic cells and vascular as well as epithelial
      basement membranes, we measured the cell adhesion-promoting activity of peptides
      from the NC1 domain of type IV collagen and their effect on proliferation of
      human melanoma cells. We found that peptide alpha3(IV)185-203
      (CNYYSNSYSFWLASLNPER) not only promotes adhesion of human melanoma cells but also
      inhibits their proliferation. Adhesion increased by 50-60% over control. Melanoma
      cell proliferation was inhibited by 40% when cells were grown in a medium
      containing 5 microg/ml peptide for 5 days. Studies showed that replacement of
      serine in position 189 or 191 by alanine resulted in significantly reduced
      adhesion. Similarly, serine replacement resulted in reduced ability to inhibit
      proliferation. Our data suggest that a region of the NC1 domain of the alpha3(IV)
      chain, contained within the sequence 185-203, not only specifically promotes
      adhesion but also inhibits proliferation of melanoma cells. These properties
      appear to be dependent on the presence of the triplet sequence -SNS- (residues
      189-191), which is unique to the alpha3 chain and may represent an important
      functional epitope.

PMID- 9252348
TI  - Phosphate transport in yeast vacuoles.
AB  - The vacuole of the yeast Saccharomyces cerevisiae is a major storage compartment
      for phosphate. We have measured phosphate transport across the vacuolar membrane.
      Isolated intact vacuoles take up large amounts of added [32P]phosphate by
      counterflow exchange with phosphate present in the vacuoles at the time of their
      isolation. The bidirectional phosphate transporter has an intrinsic dissociation
      constant for phosphate of 0.4 mM. Exchange mediated by this carrier is faster
      than unidirectional efflux of phosphate from the vacuoles. The transporter is
      highly selective for phosphate; of other anions tested, only arsenate is also a
      substrate. Transport is strongly pH-dependent with increasing activity at lower
      pH. Similar phosphate transport behavior was observed in right-side-out vacuolar
      membrane vesicles.

PMID- 9252347
TI  - Identification of an ecto-nucleoside diphosphokinase and its contribution to
      interconversion of P2 receptor agonists.
AB  - The P2Y4 receptor is selectively activated by UTP. Although addition of neither
      ATP nor UDP alone increased intracellular Ca2+ in 1321N1 human astrocytoma cells
      stably expressing the P2Y4 receptor, combined addition of these nucleotides
      resulted in a slowly occurring elevation of Ca2+. The possibility that the
      stimulatory effect of the combined nucleotides reflected formation of UTP by an
      extracellular transphosphorylating activity was investigated. Incubation of cells
      with [3H]UDP or [3H]ADP under conditions in which cellular release of ATP
      occurred or in the presence of added ATP resulted in rapid formation of the
      corresponding triphosphates. Transfer of the gamma-phosphate from [gamma-33P]ATP
      to nucleoside diphosphates confirmed that the extracellular enzymatic activity
      was contributed by a nucleoside diphosphokinase. The majority of this activity
      was associated with the cell surface of 1321N1 cells, suggesting involvement of
      an ectoenzyme. Both ADP and UDP were effective substrates for
      transphosphorylation. Since ecto-nucleotidase(s) has been considered previously
      to be the primary enzyme(s) responsible for metabolism of extracellular
      nucleotides, the relative rates of hydrolysis of ATP, ADP, UTP, and UDP also were
      determined for 1321N1 cells. All four nucleotides were hydrolyzed with similar Km
      and Vmax values. Kinetic analyses of the ecto-nucleoside diphosphokinase and ecto
      nucleotidase activities indicated that the rate of extracellular
      transphosphorylation exceeds that of nucleotide hydrolysis by up to 20-fold.
      Demonstration of the existence of a very active ecto-nucleoside diphosphokinase
      together with previous observations that stress-induced release of ATP occurs
      from most cell types indicates that transphosphorylation is physiologically
      important in the extracellular metabolism of adenine and uridine nucleotides.
      Since the P2Y receptor class of signaling proteins differs remarkably in their
      respective specificity for adenine and uridine nucleotides and di- and
      triphosphates, these results suggest that extracellular interconversion of
      adenine and uridine nucleotides plays a key role in defining activities in
      nucleotide-mediated signaling.

PMID- 9252349
TI  - Localization of a binding site for the proteoglycan decorin on collagen XIV
      (undulin).
AB  - Through its ability to bind extracellular matrix constituents and growth factors
      the small leucine-rich chondroitin/dermatan sulfate proteoglycan decorin which is
      present in many types of connective tissues may play an important biological role
      in remodeling and maintenance of extracellular matrices during inflammation,
      fibrosis, and cancer growth. In this study we investigated the known binding of
      decorin to human collagen XIV. This binding was unaffected when the small
      collagenous moiety of collagen XIV was removed with collagenase. Therefore,
      fragments covering the large noncollagenous domain NC3 of collagen XIV were
      expressed in Escherichia coli, each fused to a 26-kDa fragment of glutathione S
      transferase. Using radioiodinated decorin as ligand for the immobilized fusion
      proteins, a binding site that interacted with the decorin core protein could be
      assigned to the NH2-terminal fibronectin type III repeat of collagen XIV. In
      addition, an auxiliary binding site located COOH-terminal to this fibronectin
      type III repeat interacted with the glycosaminoglycan component of decorin.

PMID- 9252350
TI  - Determinants of HIV-1 coreceptor function on CC chemokine receptor 3. Importance
      of both extracellular and transmembrane/cytoplasmic regions.
AB  - The chemokine receptors CXCR4, CCR2b, CCR3, and CCR5 are cell entry coreceptors
      for HIV-1. Using an HIV-1 envelope (Env)-dependent cell-cell fusion model of
      entry, we show that CCR3 can interact with Envs from certain macrophage (M)
      tropic strains (which also use CCR5), T cell line (TCL)-tropic laboratory-adapted
      strains (which also use CXCR4), and a dual-tropic primary isolate (which also
      uses CCR2b, CCR5, and CXCR4). Paradoxically, CCR1 is the closest homologue to
      CCR3 (63% amino acid identity), but lacked HIV-1 coreceptor activity. These
      results confirm and extend previous reports. Replacing the N-terminal segment of
      CCR3 with that of CCR1 abolished activity of the resulting chimera for M-tropic
      and TCL-tropic Envs, but not for the dual-tropic Env. Replacing extracellular
      loop 2 of CCR3 with that of CCR1 abolished activity for TCL-tropic Envs, but not
      for M- and dual-tropic Envs. A chimera containing all four extracellular regions
      of CCR3 on a backbone of CCR1 lacked any activity. Env-CCR3 interactions were
      strongly inhibited by the major CCR3 ligand eotaxin, but weakly or not at all by
      other CCR3 ligands. With primary macrophages, eotaxin induced transient calcium
      flux and partially inhibited fusion with cells expressing M-tropic Envs. We
      conclude that specificity determinants for different Envs are located in shared
      and distinct extracellular regions of CCR3, the transmembrane/cytoplasmic domains
      make major contributions to coreceptor function, and CCR3 may be used by certain
      HIV-1 strains as a cell fusion factor on macrophages.

PMID- 9252351
TI  - The degradation of apolipoprotein B100 is mediated by the ubiquitin-proteasome
      pathway and involves heat shock protein 70.
AB  - Apolipoprotein B (apoB) is the major protein component of atherogenic
      lipoproteins of hepatic origin. In HepG2 cells, the standard cell culture model
      of human hepatic lipoprotein metabolism, there is a limited availability of core
      lipids in the endoplasmic reticulum for association with nascent apoB. Under
      these conditions, apoB is partially translocated, interacts with cytosolic Hsp70,
      and undergoes rapid degradation. We show that increasing the expression of Hsp70
      in HepG2 cells promotes apoB degradation. In addition, apoB is polyubiquitinated
      and its degradation both normally and after Hsp70 induction is blocked by
      inhibitors of the proteasome. The apoB that accumulates after proteasome
      inhibition is endoplasmic reticulum-associated and can be assembled into
      lipoproteins and secreted if new lipid synthesis is stimulated. Thus, apoB is the
      first example of a wild-type mammalian protein whose secretion is regulated by
      degradation in the cytosol via the ubiquitin-proteasome pathway. Furthermore,
      targeting of this secretory protein to the proteasome is regulated by the
      molecular chaperone Hsp70 and the availability of apoB's lipid-ligands.

PMID- 9252352
TI  - Co-translational degradation of apolipoprotein B100 by the proteasome is
      prevented by microsomal triglyceride transfer protein. Synchronized translation
      studies on HepG2 cells treated with an inhibitor of microsomal triglyceride
      transfer protein.
AB  - We studied the effect of inhibition of microsomal triglyceride transfer protein
      (MTP) on apolipoprotein (apo) B100 translation and secretion using HepG2 cells.
      The MTP-mediated lipid transfer activity was reduced using a specific MTP
      inhibitor. ApoB100 translation was synchronized by treatment with puromycin prior
      to L-[35S]methionine pulse-chase labeling. During the first 4 min of chase,
      synthesis of apoB polypeptides the size of 100-200 kDa was insensitive to the
      inhibitor, suggesting that inhibition of MTP did not affect the initiation of
      apoB100 translation. After 15 min of chase, the 100-200-kDa species were chased
      into polypeptides larger than 320 kDa (i.e. apoB65 or 65% of full-length apoB100)
      in both control and inhibitor-treated cells. However, the amount of these
      polypeptides decreased (by 36% for apoB65-75, by 64% for apoB75-85, by 76% for
      apoB85-95, and by 77% for apoB100) upon MTP inhibition. No accumulation of
      smaller polypeptides was observed, but total immunoprecipitable apoB
      radioactivity was decreased suggesting that apoB could undergo co-translational
      degradation when MTP activity was reduced. Inhibitors of the multicatalytic
      proteinase complex (proteasome) such as lactacystin or MG-115 could prevent apoB
      co-translational degradation. Nevertheless, MG-115 could not avoid the MTP
      inhibitor decreasing apoB100 secretion but rather induced the accumulation of
      secretion-incompetent apoB100 in the cell. These results indicate that MTP
      activity is required during the elongation of apoB100 polypeptides, particularly
      at the sequences downstream of carboxyl terminus of apoB65. Co-translational
      degradation might constitute a more general mechanism of early quality control
      for large or complex proteins.

PMID- 9252353
TI  - Gelsolin binding to phosphatidylinositol 4,5-bisphosphate is modulated by calcium
      and pH.
AB  - The actin cytoskeleton of nonmuscle cells undergoes extensive remodeling during
      agonist stimulation. Lamellipodial extension is initiated by uncapping of actin
      nuclei at the cortical cytoplasm to allow filament elongation. Many actin
      filament capping proteins are regulated by phosphatidylinositol 4,5-bisphosphate
      (PIP2), which is hydrolyzed by phospholipase C. It is hypothesized that PIP2
      dissociates capping proteins from filament ends to promote actin assembly.
      However, since actin polymerization often occurs at a time when PIP2
      concentration is decreased rather than increased, capping protein interactions
      with PIP2 may not be regulated solely by the bulk PIP2 concentration. We present
      evidence that PIP2 binding to the gelsolin family of capping proteins is enhanced
      by Ca2+. Binding was examined by equilibrium and nonequilibrium gel filtration
      and by monitoring intrinsic tryptophan fluorescence. Gelsolin and CapG affinity
      for PIP2 were increased 8- and 4-fold, respectively, by microM Ca2+, and the Ca2+
      requirement was reduced by lowering the pH from 7.5 to 7.0. Studies with the NH2-
      and COOH-terminal halves of gelsolin showed that PIP2 binding occurred primarily
      at the NH2-terminal half, and Ca2+ exposed its PIP2 binding sites through a
      change in the COOH-terminal half. Mild acidification promotes PIP2 binding by
      directly affecting the NH2-terminal sites. Our findings can explain increased
      PIP2-induced uncapping even as the PIP2 concentration drops during cell
      activation. The change in gelsolin family PIP2 binding affinity during cell
      activation can impact divergent PIP2-dependent processes by altering PIP2
      availability. Cross-talk between these proteins provides a multilayered mechanism
      for positive and negative modulation of signal transduction from the plasma
      membrane to the cytoskeleton.

PMID- 9252354
TI  - Light-harvesting chlorophyll a/b-binding protein stably inserts into etioplast
      membranes supplemented with Zn-pheophytin a/b.
AB  - Light-harvesting chlorophyll a/b-binding protein, LHCP, or its precursor, pLHCP,
      cannot be stably inserted into barley etioplast membranes in vitro. However, when
      these etioplast membranes are supplemented with the chlorophyll analogs Zn
      pheophytin a/b, synthesized in situ from Zn-pheophorbide a/b and digeranyl
      pyrophosphate, pLHCP is inserted into a protease-resistant state. This proves
      that chlorophyll is the only component lacking in etioplast membranes that is
      necessary for stable LHCP insertion. Synthesis of Zn-pheophytin b alone promotes
      insertion of LHCP in vitro into a protease-resistant state, whereas synthesis of
      Zn-pheophytin a alone does not. Insertion of pLHCP into etioplast membranes can
      also be stimulated by adding chlorophyll a and chlorophyll b to the membranes,
      albeit at a significantly lower efficiency as compared with Zn-pheophytin a/b
      synthesized in situ. When pLHCP is inserted into chlorophyll- or Zn-pheophytin
      supplemented etioplast membranes and then assayed with protease, only the
      protease digestion product indicative of the monomeric major light-harvesting
      chlorophyll a/b complex (LHCII) is found but not the one indicating trimeric
      complexes. In this respect, chlorophyll- or Zn-pheophytin-supplemented etioplast
      membranes resemble thylakoid membranes at an early greening stage: pLHCP inserted
      into plastid membranes from greening barley is assembled into trimeric LHCII only
      after more than 1 h of greening.

PMID- 9252355
TI  - Optimal subsite occupancy and design of a selective inhibitor of urokinase.
AB  - Human urokinase type plasminogen activator (u-PA) is a member of the chymotrypsin
      family of serine proteases that can play important roles in both health and
      disease. We have used substrate phage display techniques to characterize the
      specificity of this enzyme in detail and to identify peptides that are cleaved
      840-5300 times more efficiently by u-PA than peptides containing the
      physiological target sequence of the enzyme. In addition, unlike peptides
      containing the physiological target sequence, the peptide substrates selected in
      this study were cleaved as much as 120 times more efficiently by u-PA than by
      tissue type plasminogen activator (t-PA), an intimately related enzyme. Analysis
      of the selected peptide substrates strongly suggested that the primary sequence
      SGRSA, from position P3 to P2', represents optimal subsite occupancy for
      substrates of u-PA. Insights gained in these investigations were used to design a
      variant of plasminogen activator inhibitor type 1, the primary physiological
      inhibitor of both u-PA and t-PA, that inhibited u-PA approximately 70 times more
      rapidly than it inhibited t-PA. These observations provide a solid foundation for
      the design of highly selective, high affinity inhibitors of u-PA and,
      consequently, may facilitate the development of novel therapeutic agents to
      inhibit the initiation and/or progression of selected human tumors.

PMID- 9252356
TI  - Mitogen-activated protein kinase and cyclin B/Cdc2 phosphorylate Xenopus nuclear
      factor 7 (xnf7) in extracts from mature oocytes. Implications for regulation of
      xnf7 subcellular localization.
AB  - Xenopus nuclear factor 7 (xnf7) is a maternally expressed putative transcription
      factor that exhibits phosphorylation-dependent changes in subcellular
      localization during early Xenopus development. Xnf7 is localized to the germinal
      vesicle (nucleus) of immature oocytes in a hypophosphorylated state. Xnf7 is
      phosphorylated during oocyte maturation and released to the cytoplasm. The
      protein is retained in the cytoplasm during early embryonic cleavage stages but
      returns to nuclei at the mid-blastula transition. Xnf7 is phosphorylated at two
      sites during oocyte maturation, designated P1, consisting of one threonine at
      position 103, and P2, consisting of three clustered threonines at positions 209,
      212, and 218. Phosphorylation of both sites is important in regulating xnf7
      localization. The P1 site can be phosphorylated by cyclin B/Cdc2 in vitro. To
      further understand the mechanisms regulating subcellular localization of xnf7
      during early development, kinases capable of catalyzing phosphorylation of the P2
      site were purified from mature oocyte extracts. We found that mitogen-activated
      protein kinase phosphorylated Thr212 and cyclin B/Cdc2 phosphorylated Thr 209 and
      Thr212. No other kinase in mature oocyte extracts phosphorylated the xnf7 P2 site
      to a significant extent. These results implicate mitogen-activated protein kinase
      and cyclin B/Cdc2 in regulating xnf7 localization during oocyte maturation. This
      also suggests that localization of xnf7 may be regulated by multiple kinase
      activation pathways.

PMID- 9252357
TI  - Identification and sequence analysis of two new members of the SKALP/elafin and
      SPAI-2 gene family. Biochemical properties of the transglutaminase substrate
      motif and suggestions for a new nomenclature.
AB  - The human epithelial proteinase inhibitor SKALP/elafin and the porcine sodium
      potassium ATPase inhibitor SPAI-2 are two highly homologous proteins that share
      an NH2-terminal transglutaminase substrate domain and a COOH-terminal whey acidic
      protein (WAP) domain. Here we describe the bovine and simian orthologs of
      SKALP/elafin as well as two new bovine family members that are designated Trappin
      4 and Trappin-5 on the basis of a new nomenclature that we propose (Trappin =
      TRansglutaminase substrate and WAP motif-containing ProteIN). Sequence analysis
      of Trappin-4 and Trappin-5 revealed a domain structure that is very similar to
      SPAI-2 (Trappin-1) and SKALP/elafin (Trappin-2). The transglutaminase substrate
      motifs are conserved although the number of repeats varies among species and
      among family members. The sequence of Trappin-4 and Trappin-5 diverges from
      Trappin-1 and Trappin-2 at the putative reactive site in the WAP domain. The
      bovine ortholog of Trappin-2 is expressed in tongue and snout epidermis; Trappin
      4 is expressed in trachea, ileum, and tongue; and Trappin-5 is expressed at low
      levels in trachea, as determined by RNase protection and Northern blot analysis.
      Based on the analysis of 67 transglutaminase substrate repeats as present in all
      known Trappin gene family members from four different mammalian species a
      consensus sequence could be established: Gly-Gln-Asp-Pro-Val-Lys (GQDPVK). Using
      biotinylated hexapeptide probes we found that the GQDPVK sequence is a very
      efficient transglutaminase substrate both for guinea pig liver transglutaminase
      and for epidermal transglutaminase, and it acts as acyl donor as well as
      acceptor. We propose that the Trappin protein family forms a new group of enzyme
      inhibitors with various specificities of the WAP domain, which share
      transglutaminase substrate motifs that can act as an anchoring sequence.

PMID- 9252358
TI  - Preparation and characterization of recombinant tissue inhibitor of
      metalloproteinase 4 (TIMP-4).
AB  - TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and
      cloned (Greene, J., Wang, M., Raymond, L. A., Liu, Y. E., Rosen, C., and Shi, Y.
      E. (1996) J. Biol. Chem. 271, 30375-30380). In this report, the production and
      characterization of recombinant TIMP-4 (rTIMP4p) are described. rTIMP4p,
      expressed in baculovirus-infected insect cells, was purified to homogeneity by a
      combination of cation exchange, hydrophobic, and size-exclusion chromatographies.
      The purified protein migrated as a single 23-kDa band in SDS-polyacrylamide gel
      electrophoresis and in Western blot using a specific anti-TIMP-4 antibody.
      Inhibition of matrix metalloproteinase (MMP) activities by rTIMP4p was
      demonstrated in five MMPs. Enzymatic kinetic studies revealed IC50 values
      (concentration at 50% inhibition) of 19, 3, 45, 8, and 83 nM for MMP-1, MMP-2,
      MMP-3, MMP-7, and MMP-9, respectively. Purified rTIMP4p demonstrated a strong
      inhibitory effect on the invasion of human breast cancer cells across
      reconstituted basement membranes. Thus, TIMP-4 is a new enzymatic inhibitor in
      MMP-mediated extracellular matrix degradation and may have therapeutic potential
      in treating cancer malignant progression.

PMID- 9252359
TI  - Characterization of a diamine exporter in Chinese hamster ovary cells and
      identification of specific polyamine substrates.
AB  - Export of the diamine putrescine was studied using inside-out plasma membrane
      vesicles prepared from Chinese hamster cells. Putrescine uptake into vesicles was
      a saturable and an ATP- and antizyme-independent process. Excess amounts of a
      series of diamines or monoacetyl spermidine, but not monoacetyl putrescine,
      spermidine, or spermine, inhibited putrescine transport. Putrescine uptake into
      vesicles prepared at pH 7.4 was suppressed at pH 5, compared with pH 7.4; was
      stimulated approximately 2.5-fold at pH 7.4 in vesicles prepared at pH 6.25,
      compared with vesicles prepared at pH 7.4; and was not inhibited by valinomycin
      in the presence of potassium ions. Reserpine and verapamil blocked [3H]putrescine
      uptake into inverted vesicles. Verapamil treatment caused an increase in
      intracellular contents of putrescine, cadaverine, and N8-acetylspermidine, in
      unstressed proliferating cells, or of N1-acetylspermidine, in cells subjected to
      heat shock to induce acetylation of spermidine at N1. These data indicate that
      putrescine export in Chinese hamster cells is mediated by a non-electrogenic
      antiporter capable of using protons as the counter ion. Physiological substrates
      for this exporter include putrescine, cadaverine, and monoacetyl spermidine and
      have the general structure NH3+-(CH2)n-NH2 + R at acidic or neutral pH.

PMID- 9252360
TI  - Apoptosis induced by withdrawal of trophic factors is mediated by p38 mitogen
      activated protein kinase.
AB  - p38 is a member of the mitogen-activated protein (MAP) kinase superfamily
      activated by stress signals and implicated in cellular processes involving
      inflammation and apoptosis. Unlike the extracellular signal-regulated kinases
      (p42 and p44 MAP kinases), which are stimulated by insulin in many cell types,
      p38 activity is inhibited by insulin in postmitotic fetal neurons for which
      insulin is a potent survival factor (Heidenreich, K. A., and Kummer, J. L. (1996)
      J. Biol. Chem. 271, 9891-9894). These data suggested that insulin's effects on
      neuronal survival are mediated by inhibition of a p38-mediated apoptotic pathway.
      To better understand the relationship between p38 activity and cell survival, we
      induced apoptosis in two cell lines and examined the ability of insulin or a
      specific p38 inhibitor (a pyridinyl imidazole compound PD169316) to block p38
      activity and cell death. In Rat-1 fibroblasts grown in the presence of serum, p38
      activity was undetectable by immune complex assays, and the number of apoptotic
      cells was very low (<0.5%). After the removal of serum for 16 h, p38 activity was
      markedly elevated, and apoptosis increased by 14-15-fold. Insulin (50 ng/ml)
      inhibited p38 activity by approximately 70% and blocked apoptosis by at least
      80%. PD169316 also blocked p38 enzyme activity and apoptosis by approximately
      80%. Similar results were obtained in differentiated PC12 cells that were
      deprived of nerve growth factor (NGF) for 16 h. In the presence of NGF, p38
      activity and the number of apoptotic cells was very low (approximately 1.0%).
      After NGF withdrawal, p38 activity was selectively elevated and apoptosis
      increased to 15%. Both insulin and PD169316 markedly blocked the increase in p38
      activity and apoptosis. The MAP kinase kinase inhibitor, PD98059, had no effect
      on apoptosis in Rat-1 fibroblasts and only partially blocked apoptosis in PC12
      cells. PD98059 did not influence insulin's ability to block apoptosis, indicating
      that the extracellular signal-regulated kinase pathway does not mediate insulin's
      survival effects. These data further support the role of p38 in cellular
      apoptosis and support the hypothesis that insulin promotes cell survival, at
      least in part, by inhibiting the p38 pathway.

PMID- 9252361
TI  - Conversion of non-allosteric pyruvate kinase isozyme into an allosteric enzyme by
      a single amino acid substitution.
AB  - Pyruvate kinase M1, a non-allosteric isozyme, was converted into an allosteric
      enzyme by replacement of an amino acid in the intersubunit contact. The
      substitution of Ala-398 with Arg resulted in the pronounced allosteric enzyme.
      The Hill coefficient and the substrate concentration giving one-half of Vmax for
      the mutant with respect to phosphoenolpyruvate were 2.7 and 0.41 mM,
      respectively, whereas those values for the wild type were 1.0 and 0.049 mM. This
      mutation, however, gave rise to only minor effects on the apparent values of Km
      for ADP and on Vmax. Furthermore, in contrast to the wild-type enzyme, the mutant
      was activated by fructose 1, 6-bisphosphate. The Hill coefficient of the mutant
      was no longer increased by the allosteric inhibitor, L-phenylalanine, indicating
      that the equilibrium for the unligated enzyme is largely shifted toward the T
      state. These results suggest that Ala-398 is one of the most critical residues
      allowing the enzyme to prefer the R-state and that allosteric regulation of
      pyruvate kinase involves amino acid residues in the intersubunit contact.

PMID- 9252362
TI  - Murine laminin alpha3A and alpha3B isoform chains are generated by usage of two
      promoters and alternative splicing.
AB  - We already identified two distinct laminin alpha3A and alpha3B chain isoforms
      which differ in their amino-terminal ends and display different tissue-specific
      expression patterns. In this study we have investigated whether these two
      different isoforms are products of the same laminin alpha3 (lama3) gene and
      transcribed from one or two separate promoters. Genomic clones were isolated that
      encompass the sequences upstream to the 5' ends of both the alpha3A and the
      alpha3B cDNAs. Sequence analysis of the region upstream to the alpha3A open
      reading frame revealed the presence of a TATA box and potential binding sites for
      responsive elements. By primer extension analysis, the transcription start site
      of the alpha3B mRNA isoform was defined. The sequences upstream to the alpha3B
      mRNA transcription start site do not contain a TATA box near the transcription
      initiation sites, but AP-1, AP-2, and Sp1 consensus binding site sequences were
      identified. The genomic regions located immediately upstream of the alpha3A and
      alpha3B transcription start sites were shown to possess promoter activities in
      transfection experiments. In the promoter regions, response elements for the
      acute phase reactant signal and NF-interleukin 6 were found, and their possible
      relevance in the context of inflammation and wound healing is discussed. Our
      results demonstrate that the lama3 gene produces the two polypeptides by
      alternative splicing and contains two promoters, which regulate the production of
      the two isoforms alpha3A and alpha3B.

PMID- 9252363
TI  - Specific binding of the chemokine platelet factor 4 to heparan sulfate.
AB  - Platelet factor 4 is a tetrameric heparin binding chemokine released from the
      alpha-granules of activated platelets. In this study we show that platelet factor
      4 binds with high affinity and specificity to an approximately 9-kDa sequence in
      heparan sulfate, which it protects from degradation by heparinase enzymes. This
      protected fragment is enriched in N-sulfated disaccharides and iduronate 2-O
      sulfate residues, the latter being important for binding to platelet factor 4.
      The major structural motif of the fragment appears to consist of a pair of
      sulfated domains positioned at both ends separated by a central mainly N
      acetylated region. On the basis of these findings, we propose a model in which
      the heparan sulfate fragment wraps around the ring of positive charges on
      platelet factor 4 with the iduronate 2-O-sulfates within the sulfated domains
      binding strongly to lysine clusters on opposite faces of the tetramer.

PMID- 9252364
TI  - Reconstitution of functional voltage-gated chloride channels from complementary
      fragments of CLC-1.
AB  - We investigated the effect of truncations on the human muscle chloride channel
      CLC-1 and studied the functional complementation from partial proteins. Almost
      complete deletion of the cytoplasmic amino terminus did not affect currents, but
      truncating the intracellular COOH terminus after Leu720 abolished function.
      Currents were restored by coexpressing this membrane-embedded part with the
      lacking cytoplasmic fragment that contains domain D13, the second of the two
      conserved cystathionine beta-synthase (CBS) motifs present in all eukaryotic CLC
      proteins. However, if the cut was after Gln597 before the first CBS domain, no
      functional complementation was seen. Complementation was also obtained with
      channels "split" between transmembrane domains D7 and D8 or domains D8 and D9,
      but not when split between D10 and D11. Specificity of currents was tested by
      inserting point mutations in NH2-terminal (G188A and G230E) or COOH-terminal
      (K585E) fragments. In contrast to G188A and K585E, split channels did not
      tolerate the D136G mutation, suggesting that it may impede association from
      nonlinked fragments. Duplication, but not a lack of domain D8 was tolerated in
      "split" channels. Membrane domains D9-D12 can insert into the membrane without
      adding a preceding signal peptide to ensure the extracellular amino terminus of
      D9. Eventually, we succeeded in reconstituting CLC-1 channels from three separate
      polypeptides: the amino-terminal part up to D8, D9 through CBS1, and the
      remainder of the cytoplasmic carboxyl terminus. In summary, several regions of
      CLC channels behave autonomously regarding membrane insertion and folding and
      mediate protein-protein interactions strong enough to yield functional channels
      without a direct covalent link.

PMID- 9252365
TI  - The rat pyruvate carboxylase gene structure. Alternate promoters generate
      multiple transcripts with the 5'-end heterogeneity.
AB  - Pyruvate carboxylase (EC 6.4.1.1) is a biotin-containing enzyme that plays an
      important role in gluconeogenesis and lipogenesis. Here we report the structural
      organization of the rat pyruvate carboxylase gene, which spans over 40 kilobases
      and is composed of 19 coding exons and 4 5'-untranslated region exons. From this
      data, it is clear that alternative splicing of the primary transcripts from two
      promoters is responsible for the occurrence of the multiple mRNA species
      previously reported (Jitrapakdee, S., Walker, M. E., and Wallace, J. C. (1996)
      Biochem. Biophys. Res. Commun. 223, 695-700). The proximal promoter, which is
      active in gluconeogenic and lipogenic tissues, contains no TATA or CAAT boxes but
      includes a sequence that is typical of a housekeeping initiator protein 1 box
      while the distal promoter contains three CAAT boxes and multiple Sp1 binding
      sites. Several potential transcription factor binding sites are found in both
      promoters. A series of 5'-nested deletion constructs of both promoters were fused
      to a firefly luciferase reporter plasmid and transiently expressed in COS-1
      cells. The results show that the 153 and 187 base pairs, preceding the
      transcription start sites of the proximal and distal promoters, respectively, are
      required for basal transcription. Insulin selectively inhibits the expression of
      the proximal promoter-luciferase reporter gene by 50% but not the distal promoter
      in COS-1 cells, suggesting the presence of an insulin-responsive element in the
      proximal promoter. A half-maximal effect was found at approximately 1 nM insulin.

PMID- 9252366
TI  - Trimeresurus stejnegeri snake venom plasminogen activator. Site-directed
      mutagenesis and molecular modeling.
AB  - The specific plasminogen activator from Trimeresurus stejnegeri venom (TSV-PA) is
      a serine proteinase presenting 23% sequence identity with the proteinase domain
      of tissue type plasminogen activator, and 63% with batroxobin, a fibrinogen
      clotting enzyme from Bothrops atrox venom that does not activate plasminogen. TSV
      PA contains six disulfide bonds and has been successfully overexpressed in
      Escherichia coli (Zhang, Y., Wisner, A., Xiong, Y. L., and Bon, C. (1995) J.
      Biol. Chem. 270, 10246-10255). To identify the functional domains of TSV-PA, we
      focused on three short peptide fragments of TSV-PA showing important sequence
      differences with batroxobin and other venom serine proteinases. Molecular
      modeling shows that these sequences are located in surface loop regions, one of
      which is next to the catalytic site. When these sequences were replaced in TSV-PA
      by the equivalent batroxobin residues none generated either fibrinogen-clotting
      or direct fibrinogenolytic activity. Two of the replacements had little effect in
      general and are not critical to the specificity of TSV-PA for plasminogen.
      Nevertheless, the third replacement, produced by the conversion of the sequence
      DDE 96a-98 to NVI, significantly increased the Km for some tripeptide chromogenic
      substrates and resulted in undetectable plasminogen activation, indicating the
      key role that the sequence plays in substrate recognition by the enzyme.

PMID- 9252367
TI  - Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is
      localized to the cytoplasmic surface of early endosomes.
AB  - Hrs is a 115-kDa double zinc finger protein that is rapidly tyrosine
      phosphorylated in growth factor-stimulated cells. However, its function remains
      unknown. Here we show that Hrs is localized to early endosomes. Intracellular
      localization of endogenous Hrs and exogenously expressed Hrs tagged with the
      hemagglutinin epitope was examined by immunofluorescence staining using anti-Hrs
      and anti-hemagglutinin epitope antibodies, respectively. Hrs was detected in
      vesicular structures and was colocalized with the transferrin receptor, a marker
      for early endosomes, but only partially with CD63, a marker for late endosomes. A
      zinc finger domain deletion mutant of Hrs was also colocalized with the
      transferrin receptor, suggesting that the zinc finger domain is not required for
      its correct localization. Immunoelectron microscopy showed that Hrs was localized
      to the cytoplasmic surface of these structures. By subcellular fractionation, Hrs
      was recovered both in the cytoplasmic and membrane fractions. The membrane
      associated Hrs was extracted from the membrane by alkali treatment, suggesting
      that it is peripherally associated with early endosomes. These results, together
      with our finding that Hrs is homologous to Vps27p, a protein essential for
      protein traffic through a prevacuolar compartment in yeast, suggest that Hrs is
      involved in vesicular transport through early endosomes.

PMID- 9252368
TI  - Stretch-induced hypertrophic growth of cardiocytes and processing of brain-type
      natriuretic peptide are controlled by proprotein-processing endoprotease furin.
AB  - When hypertrophic growth is induced in neonatal rat cardiocytes by stretching,
      the cardiocytes express high levels of brain-type natriuretic peptide (BNP) and
      the proprotein-processing enzyme furin. A BNP precursor, gammaBNP, possesses a
      furin-cleavable Arg-X-X-Arg motif, which is cleaved when gammaBNP is processed to
      form BNP-45. The Arg-X-X-Arg motif is found in many precursors of growth factors
      and growth-related proteins. To determine if furin converts gammaBNP to BNP-45 as
      well as other unidentified growth-promoting protein precursors to their active
      form that may induce hypertrophic growth in cardiocytes, we used two protease
      inhibitor systems, synthetic peptidyl chloromethyl ketones (CMK) (dec-Arg-Val-Lys
      Arg-CMK and dec-Phe-Ala-Lys-Arg-CMK; where dec is decanoyl) and vaccinia vector
      integrated native and variant alpha1-antitrypsins. The furin-specific inhibitors,
      dec-Arg-Val-Lys-Arg-CMK and variant alpha1-antitrypsin with the inhibitory
      determinant Arg-X-X-Arg, suppressed the stretch-induced hypertrophic growth of
      cardiocytes as well as the processing of gammaBNP to BNP-45. The other serine
      protease inhibitors and variant alpha1-antitrypsin against elastase, or thrombin,
      however, neither suppressed the hypertrophic growth nor prevented the processing
      of gammaBNP to BNP-45. Thus, we suggest that furin catalyzes the conversion of
      gammaBNP to BNP-45 as well as growth-promoting proproteins to their active form,
      which might induce hypertrophic growth in cardiocytes.

PMID- 9252369
TI  - Residues on both faces of the first immunoglobulin fold contribute to homophilic
      binding sites of PECAM-1/CD31.
AB  - CD31 (PECAM-1) is a member of the immunoglobulin superfamily whose extracellular
      domain is comprised of six immunoglobulin-like domains. It is widely expressed on
      endothelium, platelets, around 50% of lymphocytes, and cells of myeloid lineage.
      CD31 has been shown to be involved in interendothelial adhesion and leukocyte
      endothelial interactions, particularly during transmigration. CD31-mediated
      adhesion is complex, because CD31 is capable of mediating both homophilic and
      multiple heterophilic adhesive interactions. Here we show that the NH2-terminal
      (membrane-distal) immunoglobulin domain of CD31 is necessary but not sufficient
      to support stable homophilic adhesion. Key residues forming the binding site
      within this domain have been identified by analysis of 26 single point mutations,
      representing the most systematic analysis of a fully homophilic interaction
      between immunoglobulin superfamily family members to date. This revealed five
      mutations that affect homophilic binding. Uniquely, the residues involved are
      exposed on both faces of the immunoglobulin fold, leading us to propose a novel
      mechanism for CD31 homophilic adhesion.

PMID- 9252370
TI  - Trimeric G proteins control exocytosis in chromaffin cells. Go regulates the
      peripheral actin network and catecholamine secretion by a mechanism involving the
      small GTP-binding protein Rho.
AB  - Besides having a role in signal transduction, heterotrimeric G proteins may be
      involved in membrane trafficking events. In chromaffin cells, Go is associated
      with secretory organelles and its activation by mastoparan inhibits the ATP
      dependent priming of exocytosis. The effectors by which Go controls exocytosis
      are currently unknown. The subplasmalemmal actin network is one candidate, since
      it modulates secretion by controlling the movement of secretory granules to the
      plasma membrane. In streptolysin-O-permeabilized chromaffin cells, activation of
      exocytosis produces disassembly of cortical actin filaments. Mastoparan blocks
      the calcium-evoked disruption of cortical actin, and this effect is specifically
      inhibited by antibodies against Galphao and by a synthetic peptide corresponding
      to the COOH-terminal domain of Galphao. Disruption of actin filaments with
      cytochalasin E and Clostridium perfringens iota toxin partially reverses the
      mastoparan-induced inhibition of secretion. Furthermore, the effects of
      mastoparan on cortical actin and exocytosis are greatly reduced in cells treated
      with Clostridium botulinum C3 exoenzyme, which specifically inactivates the small
      G protein Rho. We propose that the control exerted by the granule-associated Go
      on exocytosis may be related to effects on the cortical actin network through a
      sequence of events which eventually involves the participation of Rho.

PMID- 9252371
TI  - The type V transforming growth factor beta receptor is the putative insulin-like
      growth factor-binding protein 3 receptor.
AB  - Insulin-like growth factor-binding protein 3 (IGFBP-3) has been shown to inhibit
      cell growth by IGF-dependent and -independent mechanisms. The putative cell
      surface IGFBP-3 receptor that mediates the IGF-independent growth inhibition has
      not been identified. Here we show that recombinant human IGFBP-3 inhibits 125I
      transforming growth factor (TGF)-beta1 binding to the type V TGF-beta receptor
      (Mr 400,000) in mink lung epithelial cells. We also demonstrate that the
      approximately 400-kDa 125I-IGFBP-3 affinity-labeled putative IGFBP-3 receptor is
      immunoprecipitated by specific antiserum to the type V TGF-beta receptor. The
      125I-IGFBP-3 affinity labeling of the putative receptor and IGFBP-3-induced
      growth inhibition as measured by DNA synthesis in these cells is blocked by a TGF
      beta1 peptide antagonist. The 125I-IGFBP-3 affinity-labeled putative receptor can
      only be detected in cells expressing the type V TGF-beta receptor, but not in
      cells lacking the type V TGF-beta receptor. These results indicate that the type
      V TGF-beta receptor is the putative IGFBP-3 receptor and that IGFBP-3 is a
      functional ligand for the type V TGF-beta receptor.

PMID- 9252372
TI  - Identification of cytoplasmic actin as an abundant glutaminyl substrate for
      tissue transglutaminase in HL-60 and U937 cells undergoing apoptosis.
AB  - A lysine derivative, 3-[Nalpha[Nepsilon-[2', 4'-dinitrophenyl]-amino-n-hexanoyl-L
      lysylamido]-propane-1-ol, a novel amine substrate of transglutaminases, was
      synthesized and delivered into intact HL-60 and U937 human leukemia cells to
      probe the function of the intracellular enzyme. The novel substrate compound was
      covalently incorporated into intracellular proteins in these cells expressing
      high levels of tissue transglutaminase and undergoing apoptosis following the
      induction of their differentiation with dimethyl sulfoxide and retinoic acid.
      Immunoaffinity purification and microsequencing of labeled proteins identified
      cytoplasmic actin as the main endogenous glutaminyl substrate in these cells. As
      shown by confocal image analysis, cells revealed distinct labeling of the
      microfilament meshwork structures by the novel compound as the result of the
      intracellular action of transglutaminase.

PMID- 9252373
TI  - Adenovirus E1A inhibits cardiac myocyte-specific gene expression through its
      amino terminus.
AB  - Adenovirus E1A oncoproteins inhibit muscle-specific gene expression and myogenic
      differentiation by suppressing the transcriptional activating functions of basic
      helix-loop-helix proteins. As one approach to identifying cardiac-specific gene
      regulatory proteins, we analyzed the functional regions of E1A proteins that are
      required for muscle gene repression in cardiac cells. Myocyte-specific promoters,
      including the alpha-actins and alpha-myosin heavy chain, were selectively and
      potently inhibited (>90%) by E1A, while the ubiquitously expressed beta-actin
      promoter was only partially ( approximately 30%) repressed; endogenous gene
      expression was also affected. Distinct E1A protein binding sites mediated
      repression of muscle-specific and ubiquitous actin promoters. E1A-mediated
      inhibition of beta-actin required both an intact binding site for the tumor
      repressor proteins pRb and p107 and a second E1A domain (residues 15-35). In
      contrast, cardiac-specific promoter repression required the E1A amino-terminal
      residues 2-36. The proximal skeletal actin promoter (3' to base pair -153) was a
      target for repression by E1A. Although E1A binding to p300 was not required for
      inhibition of either promoter, co-expression of p300 partially reversed E1A
      mediated transcriptional repression. We conclude that cardiac-specific and
      general promoter inhibition by E1A occurs by distinct mechanisms and that cardiac
      specific gene expression is modulated by cellular factors interacting with the
      E1A p300/CBP-binding domain.

PMID- 9252375
TI  - Chemical and immunological assay of the nonreducing terminal residues of
      chondroitin sulfate from human aggrecan.
AB  - Samples of aggrecan chondroitin sulfate, isolated from normal human knee
      cartilages of individuals from fetal to 72 years of age, were digested with
      chondroitin lyases. The products were analyzed by fluorescence-based anion
      exchange high performance liquid chromatography to separate and quantitate
      nonreducing terminal structures, in addition to internal unsaturated disaccharide
      products. The predominant terminal structures were the monosaccharides, GalNAc4S
      and GalNAc4,6S as they were present on 85-90% of all chains. The remaining chains
      terminated with the disaccharides GlcAbeta1,3GalNAc4S and GlcAbeta1,3GalNAc6S.
      Marked changes in the relative abundance of these terminals were identified in
      the transition from growth cartilage to adult articular cartilage. First,
      terminal GalNAc residues were almost exclusively 4-sulfated in aggrecan from
      fetal through 15 years of age, but were approximately 50% 4,6-disulfated in
      aggrecans from adults (22-72 years of age). Second, the terminal disaccharide
      GlcAbeta1,3GalNAc4S was on approximately 7% of chains on aggrecan from fetal
      through 15 years of age, but on only approximately 3% of chains on adult
      aggrecan. In contrast, the proportion of chains terminating in
      GlcAbeta1,3GalNAc6S, approximately 9%, was unchanged from fetal to 72 years of
      age. This terminal disaccharide is proposed to be recognized by the widely used
      monoclonal antibody 3B3. However, chemical quantitation of the structure together
      with solid phase 3B3(-) immunoassay of fetal and adult aggrecans showed that the
      content of the terminal disaccharide does not necessarily correlate with
      immunoreactivity of the proteoglycan, as chain density and presentation on the
      solid phase are critical factors for recognition of chain terminals by 3B3. The
      quantitative results obtained from chemical analyses of all nonreducing termini
      of aggrecan chondroitin sulfate chains revealed important changes in chain
      termination that occur when cellular activities are altered as adult articular
      cartilage is formed after removal of growth cartilage. These findings are
      discussed in relation to specific enzymatic steps that generate the nonreducing
      termini of chains in the biosynthesis pathway of chondroitin sulfate
      proteoglycans and their modulation in tissue development and pathology.

PMID- 9252374
TI  - Mutational analysis of thrombopoietin for identification of receptor and
      neutralizing antibody sites.
AB  - Thrombopoietin (TPO) is a hematopoietin important for megakaryocyte proliferation
      and production of blood platelets. We sought to characterize how TPO binds and
      activates its receptor, myeloproliferative leukemia virus receptor. The
      erythropoietin-like domain of TPO (TPO1-153) has been fused to the gIII coat
      protein of M13 bacteriophage. Forty residues were chosen for mutation to alanine
      using the criteria that they were charged residues or predicted to be solvent
      exposed, based on a homology model. Phage enzyme-linked immunosorbent assay was
      used to determine affinities for binding to both the TPO receptor and five anti
      TPO1-153 monoclonal antibodies. Mutations at mostly positively charged residues
      (Asp8, Lys14, Lys52, Lys59, Lys136, Lys138, Arg140) caused the greatest reduction
      in receptor-binding affinity. Most of these residues mapped to helices-1 and -4
      and a loop region between helix-1 and helix-2. Two of the monoclonal antibodies
      that blocked TPO binding and bioactivity had determinants in helix-4. In
      contrast, the other three monoclonal antibodies, which were effective at blocking
      TPO activity but did not block initial binding of TPO to its receptor, had
      epitopes predominantly on helix or 3. These results suggest that TPO has two
      distinct receptor-binding sites that function to dimerize TPO receptors in a
      sequential fashion.

PMID- 9252376
TI  - Spatial orientation of the alpha and betac receptor chain binding sites on
      monomeric human interleukin-5 constructs.
AB  - Interleukin-5 (IL-5), a disulfide-linked homodimer, can be induced to fold as a
      biological active monomer by extending the loop between its third and fourth
      helices (Dickason, R. R., and Huston, D. P. (1996) Nature 379, 652-655). We have
      designed eight monomeric IL-5 proteins to optimize biological activity and
      stability of the monomer. This was achieved by (i) inserting the joining loop at
      three different positions, (ii) by introducing an additional intramolecular
      disulfide bridge onto these backbones, and (iii) by creating circular
      permutations to fix the position of the carboxyl-terminal helix relative to the
      three other helices. The proteins dimerize with Kd values ranging from 20 to 200
      microM and are therefore monomeric at the picomolar concentrations where they are
      biologically active. Introduction of a second disulfide confers increased
      stability, but this increased rigidity results in lower activity of the protein.
      Contrary to wild type IL-5, mutation of the betac contact residue on the first
      helix, Glu12, to Lys, into the circularly permutated constructs, did not abolish
      TF-1 proliferative and eosinophil activation activities. These results indicate
      that activation of the IL-5 receptor complex is not mediated solely by Glu12 on
      the first helix, and alternative mechanisms are discussed.

PMID- 9252377
TI  - Identification of common and distinct residues involved in the interaction of
      alphai2 and alphas with adenylyl cyclase.
AB  - The G protein alpha subunits, alphas and alphai2, have stimulatory and inhibitory
      effects, respectively, on a common effector protein, adenylyl cyclase. These
      effects require a GTP-dependent conformational change that involves three alpha
      subunit regions (Switches I-III). alphas residues in three adjacent loops,
      including Switch II, specify activation of adenylyl cyclase. The adenylyl cyclase
      specifying region of alphai2 is located within a 78-residue segment that includes
      two of these loops but none of the conformational switch regions. We have used an
      alanine-scanning mutagenesis approach within Switches I-III and the 78-residue
      segment of alphai2 to identify residues required for inhibition of adenylyl
      cyclase. We found a cluster of conserved residues in Switch II in which
      substitutions cause major losses in the abilities of both alphai2 and alphas to
      modulate adenylyl cyclase activity but do not affect alpha subunit expression or
      the GTP-induced conformational change. We also found two regions within the 78
      residue segment of alphai2 in which substitutions reduce the ability of alphai2
      to inhibit adenylyl cyclase, one of which corresponds to an effector-activating
      region of alphas. Thus, both alphai2 and alphas interact with adenylyl cyclase
      using: 1) conserved Switch II residues that communicate the conformational state
      of the alpha subunit and 2) divergent residues that specify particular effectors
      and the nature of their modulation.

PMID- 9252378
TI  - The binding of receptor-recognized alpha2-macroglobulin to the low density
      lipoprotein receptor-related protein and the alpha2M signaling receptor is
      decoupled by oxidation.
AB  - Receptor-recognized forms of alpha2-macroglobulin (alpha2M*) bind to two classes
      of cellular receptors, a high affinity site comprising approximately 1500
      sites/cell and a lower affinity site comprising about 60,000 sites/cell. The
      latter class has been identified as the so-called low density lipoprotein
      receptor-related protein (LRP). Ligation of receptors distinct from LRP activates
      cell signaling pathways. Strong circumstantial evidence suggests that the high
      affinity binding sites are responsible for cell signaling induced by alpha2M*.
      Using sodium hypochlorite, a powerful oxidant produced by the H2O2
      myeloperoxidase-Cl- system, we now demonstrate that binding to the high affinity
      sites correlates directly with activation of the signaling cascade. Oxidation of
      alpha2M* using 200 microM hypochlorite completely abolishes its binding to LRP
      without affecting its ability to activate the macrophage signaling cascade.
      Scatchard analysis shows binding to a single class of high affinity sites (Kd -
      71 +/- 12 pM). Surprisingly, oxidation of native alpha2-macroglobulin (alpha2M)
      with 125 microM hypochlorite results in the exposure of its receptor-binding site
      to LRP, but the ligand is unable to induce cell signaling. Scatchard analysis
      shows binding to a single class of lower affinity sites (Kd - 0.7 +/- 0.15 nM).
      Oxidation of a cloned and expressed carboxyl-terminal 20-kDa fragment of alpha2M
      (RBF), which is capable of binding to both LRP and the signaling receptor,
      results in no significant change in its binding Kd, supporting our earlier
      finding that the oxidation-sensitive site is predominantly outside of RBF.
      Attempts to understand the mechanism responsible for the selective exposure of
      LRP-binding sites in oxidized native alpha2M suggest that partial protein
      unfolding may be the most likely mechanism. These studies provide strong evidence
      that the high affinity sites (Kd - 71 pM) are the alpha2M* signaling receptor.

PMID- 9252379
TI  - Upstream stimulatory factor-2 (USF2) activity is required for glucose stimulation
      of L-pyruvate kinase promoter activity in single living islet beta-cells.
AB  - Elevated glucose concentrations stimulate L-pyruvate kinase (L-PK) gene
      transcription in liver and islet beta-cells. A glucose response element termed
      the L4 box (two noncanonical E-boxes located -165 and -154 base pairs upstream of
      the transcriptional start point) has previously been defined within the proximal
      promoter region of the gene. However, the identity of the transacting factor(s)
      which binds to this site remains unclear. We have used photon counting digital
      imaging of firefly luciferase activity to monitor promoter activity continuously
      in single living islet beta and derived INS-1 cells, and to analyze the molecular
      basis of the regulation by glucose. L-PK promoter activity, normalized to
      cytomegalovirus promoter activity using the distinct Renilla reniformis
      luciferase, was >/=6-fold higher in cells cultured at 16 mM glucose or above
      compared with cells cultured at 3 mM glucose. Microinjection of antibodies
      against the ubiquitous transcription factor USF2 inhibited L-PK promoter activity
      in beta- and INS-1 cells incubated at 30 mM glucose by 71-87%. Anti-USF2
      antibodies had a much smaller effect on promoter activity in INS-1 cells cultured
      at 3 mM glucose, and on the activity of a modified promoter construct lacking an
      L4 box. These data support the view that glucose enhances L-PK gene transcription
      in beta-cells by modifying the transactivational capacity of USF2 bound to the
      upstream L4 box.

PMID- 9252380
TI  - Generation of angiostatin by reduction and proteolysis of plasmin. Catalysis by a
      plasmin reductase secreted by cultured cells.
AB  - Extracellular manipulation of protein disulfide bonds has been implied in diverse
      biological processes, including penetration of viruses and endotoxin into cells
      and activation of certain cytokine receptors. We now demonstrate reduction of one
      or more disulfide bonds in the serine proteinase, plasmin, by a reductase
      secreted by Chinese hamster ovary or HT1080 cells. Reduction of plasmin disulfide
      bond(s) triggered proteolysis of the enzyme, generating fragments with the domain
      structure of the angiogenesis inhibitor, angiostatin. Two of the known reductases
      secreted by cultured cells are protein disulfide isomerase and thioredoxin, and
      incubation of plasmin with these purified reductases resulted in angiostatin
      fragments comparable with those generated from plasmin in cell culture.
      Thioredoxin-derived angiostatin inhibited proliferation of human dermal
      microvascular endothelial cells with half-maximal effect at approximately 0.2
      microg/ml. Angiostatin made by cells and by purified reductases contained free
      sulfhydryl group(s), and S-carbamidomethylation of these thiol group(s) ablated
      biological activity. Neither protein disulfide isomerase nor thioredoxin were the
      reductases used by cultured cells, because immunodepletion of conditioned medium
      of these proteins did not affect angiostatin generating activity. The plasmin
      reductase secreted by HT1080 cells required a small cofactor for activity, and
      physiologically relevant concentrations of reduced glutathione fulfilled this
      role. These results have consequences for plasmin activity and angiogenesis,
      particularly in the context of tumor growth and metastasis. Moreover, this is the
      first demonstration of extracellular reduction of a protein disulfide bond, which
      has general implications for cell biology.

PMID- 9252381
TI  - Nuclear factor-kappaB is activated by hyperoxia but does not protect from cell
      death.
AB  - Oxidative insults that are lethal to epithelial cells kill either via apoptosis
      or necrosis. Nuclear factor-kappaB (NF-kappaB) is a redox-sensitive transcription
      factor that is activated by oxidative insult, and NF-kappaB activation can
      protect cells from apoptosis. To test if NF-kappaB can protect from necrotic cell
      death caused by high levels of molecular O2 (hyperoxia), we exposed human
      alveolar epithelial (A549) cells to hyperoxia. NF-kappaB was shown to be
      activated and was translocated to the nucleus within minutes. Nuclear
      translocation persisted over the course of several days, and the levels of NF
      kappaB protein and mRNA increased as well. In hyperoxia, NF-kappaB regulation was
      independent of mitogen-activated protein kinase (MAPK). In sharp contrast, there
      was neither nuclear translocation of NF-kappaB nor any increase in expression
      after exposure to H2O2 at a concentration where this oxidant induces both MAPK
      and widespread apoptosis. Despite the activation and increased expression of NF
      kappaB in hyperoxia, this oxidant remained lethal to the cells. These
      observations confirm the notion that apoptosis occurs in the absence of NF-kappaB
      activation but indicate that protection from cell death by NF-kappaB is probably
      limited to apoptosis.

PMID- 9252382
TI  - Absence of the alpha1(IX) chain leads to a functional knock-out of the entire
      collagen IX protein in mice.
AB  - Cartilage fibrils contain collagen II as well as smaller amounts of collagens IX
      and XI. The three collagens are thought to co-assemble into cartilage-specific
      arrays. The precise role of collagen IX in cartilage has been addressed
      previously by generating mice harboring an inactivated Col9a1 gene encoding the
      alpha1(IX) chain, i.e. one of the three constituent chains of collagen IX
      (Fassler, R., Schnegelsberg, P. N. J., Dausman, J., Shinya, T., Muragaki, Y.,
      McCarthy, M. T., Olsen, B. R., and Jaenisch, R. (1994) Proc. Natl. Acad. Sci. U.
      S. A. 91, 5070-5074). The animals did not produce alpha1(IX) mRNA or polypeptides
      and were born with no conspicuous skeletal abnormality but post-natally developed
      early onset osteoarthritis. Here we show that the deficiency in alpha1(IX) chains
      leads to a functional knock-out of all polypeptides of collagen IX, whereas the
      Col9a2 and Col9a3 genes were normally transcribed. Therefore, synthesis of
      alpha1(IX) polypeptides is essential for the assembly of heterotrimeric collagen
      IX molecules. Surprisingly, cartilage fibrils of all shapes and banding patterns
      found in normal newborn, adolescent, or adult mice were formed in transgenic
      animals, although they lacked collagen IX. Therefore, collagen IX is not
      essential, and may be functionally redundant, in fibrillogenesis in cartilage in
      vivo. The protein is required, however, for long term tissue stability,
      presumably by mediating interactions between fibrillar and extrafibrillar
      macromolecules.

PMID- 9252384
TI  - Human phospholipase D1 can be tyrosine-phosphorylated in HL-60 granulocytes.
AB  - The human phospholipase D1 (hPLD1) has recently been cloned. Although recent data
      have implicated PLD in receptor-stimulated secretion, the regulation of the
      activity of PLD enzymes remains to be clarified. Purified hPLD1 is activated by
      several cytosolic cofactors among which are protein kinase Calpha, ARF, and RhoA.
      In human granulocytes, a strong correlation between tyrosine phosphorylation of
      proteins and PLD activity has been established. In this study, the presence of
      hPLD1 in HL-60 granulocytes and its phosphorylation on tyrosine residues have
      been studied. We generated antipeptide antibodies (Abs) specific for hPLD1 but
      not PLD2 as shown by Western blotting (WB) of recombinant PLD1 and PLD2. These
      Abs identified the presence of hPLD1 in HL-60 cells with the bulk of it being
      detected in the membranes and only a minor fraction in the cytosol. The hPLD1 Abs
      detected a major band at 120 kDa (PLD1a) and a minor band at 115 kDa (PLD1b). The
      specificity of the Abs was confirmed using PLD antisera neutralized with the
      immunizing peptides. The two forms of hPLD1 were consistently detected by
      immunoprecipitation under nondenaturing and denaturing conditions following a WB
      analysis with hPLD1 Abs. Following exposure of HL-60 cells to peroxides of
      vanadate (V4+-OOH), an inhibitor of tyrosine phosphatases, hPLD1 was
      immunoprecipitated under nondenaturing conditions from HL-60 cell lysates and
      assayed for tyrosine phosphorylation by WB. hPLD1 comigrated with a 120-kDa
      tyrosine phosphorylated protein by gel electrophoresis. Other tyrosine
      phosphorylated peptides of 160, 140, 135, 90, and 75-80 kDa were also detected in
      hPLD1 immune complexes. hPLD1 and the associated tyrosine-phosphorylated proteins
      were not immunoprecipitated by neutralized hPLD1 Abs. Using denaturing
      conditions, the PLD immunoprecipitates were sequentially immunoblotted with anti
      PLD1 and anti-phosphotyrosine Abs. PLD1a and PLD1b were detected, and the major
      PLD1a protein was superimposable with a major tyrosine-phosphorylated protein
      detected at 120 kDa. Conversely, PLD1a and PLD1b were recovered, at least in
      part, in the anti-phosphotyrosine immunoprecipitates. These results provide
      evidence that two PLD1 forms are expressed in human granulocytes. Furthermore, in
      response to stimulation by V4+-OOH, PLD1 was tyrosine-phosphorylated and
      associated with several, presently undefined, tyrosine-phosphorylated proteins.

PMID- 9252383
TI  - Presenilins are processed by caspase-type proteases.
AB  - Presenilin 1 (PS1) and presenilin 2 (PS2) are endoproteolytically processed in
      vivo and in cell transfectants to yield 27-35-kDa N-terminal and 15-24-kDa C
      terminal fragments. We have studied the cleavage of PS1 and PS2 in transiently
      and stably transfected hamster kidney and mouse and human neuroblastoma cells by
      immunoblot and pulse-chase experiments. C-terminal fragments were isolated by
      affinity chromatography and SDS-polyacrylamide gel electrophoresis and sequenced.
      The processing sites identified in PS1 and PS2 (Asp345/Ser346 and Asp329/Ser330,
      respectively) are typical for caspase-type proteases. Specific caspase inhibitors
      and cleavage site mutations confirmed the involvement of caspase(s) in PS1 and
      PS2 processing in cell transfectants. Fluorescent peptide substrates carrying the
      PS-identified cleavage sites were hydrolyzed by proteolytic activity from mouse
      brain. The PS2-derived peptide substrate was also cleaved by recombinant human
      caspase-3. Additional processing of PS2 by non-caspase-type proteases was also
      observed.

PMID- 9252385
TI  - Decrease in the amount of focal adhesion kinase (p125(FAK)) in interleukin-1beta
      stimulated human umbilical vein endothelial cells by binding of human monocytic
      cell lines.
AB  - Monocytes in the blood circulation migrate across endothelial cell monolayers
      lining the blood vessels and infiltrate into the underlying tissues in
      inflammation. However, little is known about the mechanisms by which leukocytes
      migrate across the endothelial barrier after binding and what molecules
      participate in the process. Addition of the human monocytic cell line THP-1 to
      interleukin-1beta (IL-1beta)-stimulated human umbilical vein endothelial cells
      (HUVEC) induced a decrease in the amount of focal adhesion kinase (p125(FAK))
      protein, a tyrosine kinase localized at focal contacts and essential for cell
      attachment to the extracellular matrix, whereas little change was observed in the
      amount of other molecules associated with cell adhesion such as vascular cell
      adhesion molecule-1, alpha-catenin, and talin. A maximum decrease in the amount
      of p125(FAK) was observed 15-30 min after addition of THP-1 cells to HUVEC, after
      which the level of p125(FAK) gradually recovered. A reduction in the density of
      actin stress fibers in IL-1beta-activated HUVEC was observed in parallel with the
      decrease in p125(FAK). The p125(FAK) decrease was partially inhibited by
      preventing THP-1 binding to HUVEC using a mixture of antibodies to adhesion
      molecules. We suggest that the decrease in p125(FAK) triggered by binding of
      monocytes in inflammation facilitates the transendothelial migration of the
      monocytes by altering the adhesiveness of endothelial cells to the extracellular
      matrix.

PMID- 9252386
TI  - The role of the Shc phosphotyrosine interaction/phosphotyrosine binding domain
      and tyrosine phosphorylation sites in polyoma middle T antigen-mediated cell
      transformation.
AB  - The phosphotyrosine interaction (PI)/phosphotyrosine binding (PTB) domain of Shc
      binds specific tyrosine-phosphorylated motifs found on activated growth factor
      receptors and proteins such as polyoma virus middle T antigen (MT). Phenylalanine
      198 (Phe198) has been identified as a crucial residue involved in the interaction
      of the Shc PI/PTB with phosphopeptides. In NIH 3T3 cells expressing MT, p52 Shc
      carrying the F198V mutation is weakly phosphorylated and does not bind MT or
      Grb2. Overexpression of the PI/PTB domain alone as Shc amino acids 1-238 acted in
      a dominant interfering fashion blocking MT-induced transformation. However,
      expression of a slightly longer construct, Shc 1-260, which encompasses
      Tyr239/Tyr240, a novel Shc tyrosine phosphorylation site, did not block
      transformation. This was found to be due to the ability of Shc 1-260 to become
      tyrosine-phosphorylated and bind Grb2. Furthermore, full-length Shc in which
      Tyr239/Tyr240 had been mutated to phenylalanine did not become tyrosine
      phosphorylated or bind Grb2 but did inhibit colony formation in soft agar.
      Conversely, p52 Shc carrying a mutation in the other tyrosine phosphorylation
      site, Tyr317, became heavily tyrosine-phosphorylated, bound Grb2, and gave rise
      to colonies in soft agar.

PMID- 9252387
TI  - Activated protein C cleavage of factor Va leads to dissociation of the A2 domain.
AB  - The products of cleavage of bovine factor Va by activated protein C (APC) in the
      presence and absence of phospholipid (25% phosphatidylserine, 75%
      phosphatidylcholine, PCPS) were evaluated using sedimentation
      velocity/equilibrium methods in the analytical ultracentrifuge and by
      immunoprecipitation using an antibody directed against the light chain of the
      factor Va molecule. The molecular weight and sedimentation coefficient of the
      associated heavy and light chains of factor Va, 173,000 (7.9 S) is reduced to
      132,000 (7.1 S) by APC cleavage at Arg505 and Arg662. Complete cleavage of the
      factor Va heavy chain (with APC-PCPS) at Arg505, Arg662 and Arg306 results in a
      drastic change in the molecular weight observed for the product. Two products are
      resolved with sedimentation coefficients of 3.3 and 6.3 S with estimated
      molecular weights of 48,000 and 114,000, respectively. Immunoprecipitation
      studies showed that the products of factor Va cleavage at Arg505 and Arg662
      (A1A2N.A2C.LC) are mostly noncovalently associated and consequently
      immunoprecipitated with an antibody directed against the light chain of the
      factor Va molecule. In contrast, for factor Va cleaved at Arg505, Arg662, and
      Arg306 the precipitated complex consisted of the A1 domain (residues 1-306) and
      the light chain (residues 1537-2183) of factor Va (A1.LC). The fragments
      corresponding to residues 307-505 (A2N) and 506-662 (A2C) are found in the
      supernatant. The combined mass of these two products (48,000) is similar to the
      estimated mass of the 3.3 S fragment estimated from sedimentation
      velocity/equilibrium studies; while the combined mass of the 1-306 + 1537-2183
      products corresponds to 114,000, the estimated mass of the 6.3 S fragment. These
      data lead to the conclusion that cleavages at Arg306, Arg505, and Arg662 of the
      factor Va molecule resulted in the dissociation of the entire A2 domain as two
      noncovalently associated fragments (A2N.A2C). Enzyme kinetic and light scattering
      data suggest that the complete inactivation of the factor Va molecule involves
      not only cleavage at Arg306 but also the dissociation of the A2 domain. These
      data also suggest that the complete APC inactivation of the factor Va molecule is
      analogous to the spontaneous inactivation of factor VIIIa, which occurs via the
      dissociation of the A2 domain.

PMID- 9252388
TI  - The hepatitis B virus X protein enhances the DNA binding potential and
      transcription efficacy of bZip transcription factors.
AB  - The hepatitis B virus X protein interacts with the basic-region, leucine zipper
      protein (bZip) domain of cAMP response element-binding protein increasing its
      affinity for the cAMP response element site in vitro and its transcriptional
      efficacy in vivo (Williams, J. S., and Andrisani, O. M. (1995) Proc. Natl. Acad.
      Sci. U. S. A. 92, 3819-3823). Here we examine pX interactions with bZip
      transcription factors ATF3, gadd153/Chop10, ICER IIgamma, and NF-IL6. We
      demonstrate direct interactions in vitro between pX and the bZip proteins tested.
      In contrast MyoD and Gal4(1-147) fail to interact with pX. We also demonstrate by
      the mammalian two-hybrid assay the direct interaction of pX with cAMP response
      element- binding protein, ICER IIgamma, ATF3, and NF-IL6 in hepatocytes. In
      addition, pX increases the DNA binding potential of bZip proteins for their
      cognate DNA-binding site in vitro. In transient transfections in hepatocytes
      (AML12 cell line), pX increases the transcriptional efficacy of the bZip
      transcription factors. NF-IL6-mediated transcriptional activation is enhanced 3
      fold by pX. Most interestingly, pX augments the repression mediated by bZip
      repressors ATF3 and ICER IIgamma, by 6- and 7-fold, respectively, demonstrating
      for the first time the involvement of pX in gene repression. We conclude that pX
      is an enhancer of the DNA binding potential of bZip transcription factors,
      thereby increasing the transactivation or repression efficacy of bZip-responsive
      genes.

PMID- 9252389
TI  - Signaling from G protein-coupled receptors to the c-jun promoter involves the
      MEF2 transcription factor. Evidence for a novel c-jun amino-terminal kinase
      independent pathway.
AB  - The c-Jun amino-terminal kinases (JNKs) are a subfamily of mitogen-activated
      protein kinases that phosphorylate c-Jun and ATF2, and it has been postulated
      that phosphorylated c-Jun enhances its own expression through AP-1 sites on the c
      jun promoter. In this study, we asked whether signals activating JNK regulate the
      c-jun promoter. Using NIH 3T3 cells expressing G protein-coupled m1 acetylcholine
      receptors as an experimental model, we have recently shown that the cholinergic
      agonist carbachol, but not platelet-derived growth factor, potently elevates JNK
      activity. Consistent with these findings, carbachol, but not platelet-derived
      growth factor, increased the activity of a c-jun promoter-driven reporter gene
      (for chloramphenicol acetyltransferase). However, coexpression of JNK kinase
      kinase (MEKK) effectively increased JNK activity, but resulted in surprisingly
      limited induction of the c-jun promoter. This raised the possibility that
      pathway(s) distinct from JNK control the c-jun promoter, and prompted us to
      explore which of its regulatory elements participate in transcriptional control.
      We observed that deletion of the 3' AP-1 site diminished chloramphenicol
      acetyltransferase activity in response to carbachol, but only to a limited
      extent. In contrast, deletion of a MEF2 site dramatically reduced expression, and
      deletion of both the MEF2 and 3' AP-1 sites abolished induction. Furthermore,
      cotransfection with MEF2C and MEF2D cDNAs potently enhanced the activity of the c
      jun promoter in response to carbachol, and stimulation of m1 receptors, but not
      direct JNK activation, induced expression of a MEF2-responsive plasmid. Taken
      together, these data strongly suggest that MEF2 mediates c-jun promoter
      expression by G protein-coupled receptors through a yet to be identified pathway,
      distinct from that of JNK.

PMID- 9252390
TI  - Association of phosphofructokinase-M with caveolin-3 in differentiated skeletal
      myotubes. Dynamic regulation by extracellular glucose and intracellular
      metabolites.
AB  - Caveolin-3 is a member of the caveolin family of proteins that is primarily
      expressed in striated muscle cell types (skeletal and cardiac). Here, we show
      that an approximately 80-kDa protein specifically co-immunoprecipitates with
      caveolin-3 expressed in differentiated skeletal C2C12 myotubes. Microsequence
      analysis of this approximately 80-kDa polypeptide revealed its identity as a key
      regulatory enzyme in the glycolytic pathway, namely phosphofructokinase-M (PFK
      M). Pulse-chase experiments demonstrate that PFK-M associates with caveolin-3
      with a significant time lag after the biosynthesis of PFK-M. In addition, we show
      that this interaction is (i) highly regulated by the extracellular concentration
      of glucose and (ii) can be stabilized by a number of relevant intracellular
      metabolites, such as fructose 1,6-bisphosphate and fructose 2,6-bisphosphate,
      which are known allosteric activators of PFK. While the bulk of these experiments
      were performed in C2C12 cells, identical results were obtained using mouse
      skeletal muscle extracts. Taken together, our results suggest that glucose
      dependent plasma membrane recruitment of activated PFK-M by caveolin-3 could have
      important implications for understanding the mechanisms that regulate energy
      metabolism in skeletal muscle fibers.

PMID- 9252391
TI  - Insulin-stimulated tyrosine phosphorylation of caveolin is specific for the
      differentiated adipocyte phenotype in 3T3-L1 cells.
AB  - Previous work from this laboratory has shown that insulin stimulates the tyrosine
      phosphorylation of caveolin in 3T3-L1 adipocytes (Mastick, C. C., Brady, M. J.,
      and Saltiel, A. R. (1995) J. Cell Biol. 129, 1523-1531). This phosphorylation is
      specific for insulin and involves the activation of a tyrosine kinase downstream
      of the insulin receptor. We report here that tyrosine phosphorylation of caveolin
      is detected only in fully differentiated adipocytes, not in fibroblasts
      (preadipocytes), despite the fact that both cell types express caveolin-1 and
      active insulin receptor. Caveolin copurifies with caveolin tyrosine kinase
      activity in both preadipocytes and adipocytes. Accumulating evidence indicates
      that this kinase is the Src family kinase Fyn. Fyn is expressed in the
      preadipocytes and the adipocytes and is colocalized with caveolin in low density
      Triton-insoluble complexes in both cell types. In adipocytes, overexpression of
      wild type Fyn leads to increased basal phosphorylation of caveolin and
      hyperphosphorylation of caveolin in response to insulin. In vitro kinase assays
      suggest that Fyn may be activated in response to insulin through the binding of a
      tyrosine-phosphorylated insulin receptor substrate protein. Previous work
      suggested that this protein may be c-Cbl (Ribon, V., and Saltiel, A. R. (1997)
      Biochem. J. 324, 839-846). In 3T3-L1 adipocytes, Cbl binds to Fyn in an insulin
      dependent manner, and Cbl phosphorylation is adipocyte-specific. Here we show
      that phosphorylated Cbl is translocated into caveolin-enriched Triton-insoluble
      complexes after insulin stimulation. This may lead to the cell type-specific,
      compartmentalized activation of Fyn and the specific phosphorylation of proteins
      in the caveolae in response to insulin in adipocytes.

PMID- 9252392
TI  - Genomic deletion of an imprint maintenance element abolishes imprinting of both
      insulin-like growth factor II and H19.
AB  - Insulin-like growth factor II (Igf2) is maternally imprinted in normal tissues
      with only the paternal copy of the gene being transcribed, whereas the contiguous
      gene H19 is paternally imprinted. Dysregulation of IGF2 imprinting is commonly
      observed in Wilms' tumor and other human tumors. Previous work comparing promoter
      specific imprinting of human and mouse Igf2 suggested the presence of a cis
      element upstream of Igf2 that regulates or maintains the imprinting of three
      downstream promoters. To explore the molecular mechanism of maintenance of
      genomic imprinting, we targeted the region between insulin 2 and Igf2, where the
      cis imprint maintenance element (IME) resides in mouse fibroblasts. In those
      clones in which the targeting vector was randomly integrated into the genome,
      mouse Igf2 remained imprinted. However, when the targeted region containing the
      IME was deleted by homologous recombination, whether from the paternal or
      maternal allele, activation of the imprinted maternal allele of Igf2 was
      observed. In addition, there was a loss of H19 imprinting when the IME was
      deleted. The requirement of IME from both parental alleles for the maintenance of
      genomic imprinting thus suggests the importance of a spatial structure of DNA
      around Igf2 and H19. Modifications in the IME, like abnormal methylation in
      Wilms' tumors, may represent a novel mechanism for loss of genomic imprinting.

PMID- 9252393
TI  - Increased tissue factor-initiated prothrombin activation as a result of the
      Arg506 --> Gln mutation in factor VLEIDEN.
AB  - The effect of the Arg506 --> Gln mutation in factor VLEIDEN on thrombin
      generation was evaluated in a reconstituted system using the purified components
      of the tissue factor (TF) pathway to thrombin and the components of the protein C
      pathway. Recombinant full-length tissue factor pathway inhibitor (RTFPI) was
      included in the system because of a previously observed synergistic inhibitory
      effect of TFPI and the protein C pathway on TF-initiated thrombin generation.
      Thrombin generation initiated by 1.25 pM factor VIIa.TF in the absence of the
      protein C pathway components occurs following an initiation phase, after which
      prothrombin is quantitatively converted to 1.4 microM thrombin. The factor
      VLEIDEN mutation did not influence thrombin generation in the reconstituted model
      in the absence of the protein C pathway. In the presence of 2.5 nM TFPI, 65 nM
      protein C, and 10 nM recombinant soluble thrombomodulin (Tm), thrombin generation
      catalyzed by normal factor V was abolished after the initial formation of 25 nM
      thrombin. In contrast, persistent thrombin generation was observed in the
      presence of factor VLEIDEN in the same system, although the rate of thrombin
      generation was slower compared with the reaction without protein C and Tm. The
      rate of thrombin generation with factor VLEIDEN increased with time and
      ultimately resulted in quantitative prothrombin activation. When the TFPI
      concentration was reduced to 1.25 nM, thrombin generation is still curtailed in
      the presence of normal factor V. In contrast, under similar conditions using
      factor VLEIDEN, the protein C pathway totally failed to down-regulate thrombin
      generation. The dramatic effect of a 50% reduction in TFPI concentration on the
      inhibitory potential of the protein C pathway on thrombin generation catalyzed by
      factor VLEIDEN suggests that the observed synergy between TFPI and the protein C
      pathway is directly governed by the TFPI concentration and by cleavage of the
      factor Va heavy chain at Arg506. This cleavage appears to have a dramatic
      regulatory effect in the presence of low concentrations of TFPI. Markedly
      increased thrombin generation in the presence of both 1.25 nM TFPI and factor
      VLEIDEN was also observed when antithrombin-III was added to the system to
      complete the natural set of coagulation inhibitors. Protein S (300 nM) had a
      minimal effect in the model on the inhibition of thrombin generation by protein
      C, Tm, and TFPI, with either normal factor V or factor VLEIDEN. Protein S also
      failed to significantly potentiate the action of the protein C pathway in the
      presence of antithrombin-III in reactions employing normal factor V or factor
      VLEIDEN. The absence of an effect of protein S in the model, which employs
      saturating concentrations of phospholipid, suggests that the reported
      interactions of protein S with coagulation factors are not decisive in the
      reaction. Altogether the data predict that TFPI levels in the lower range of
      normal values are a risk factor for thrombosis when combined with the Arg506 -->
      Gln mutation in factor VLEIDEN.

PMID- 9252394
TI  - Differential recognition of preproteins by the purified cytosolic domains of the
      mitochondrial import receptors Tom20, Tom22, and Tom70.
AB  - The preprotein translocase of the outer mitochondrial membrane (Tom) is a multi
      subunit complex required for specific recognition and membrane translocation of
      nuclear-encoded preproteins. We have expressed and purified the cytosolic domains
      of three postulated import receptors, Tom20, Tom22, and Tom70. Each receptor
      domain is able to bind mitochondrial preproteins but with different specificity.
      Tom20 binds both preproteins with N-terminal presequences and preproteins with
      internal targeting signals; the binding is enhanced by the addition of salt.
      Tom22 selectively recognizes presequence-carrying preproteins in a salt-sensitive
      manner. Tom70 preferentially binds preproteins with internal targeting
      information. A chemically synthesized presequence peptide competes with
      preproteins for binding to Tom20 and Tom22 but not to Tom70. We conclude that
      each of the three import receptors binds preproteins independently and by a
      different mechanism. Both Tom20 and Tom22 function as presequence receptors.

PMID- 9252395
TI  - A common mechanism underlying the E1A repression and the cAMP stimulation of the
      H ferritin transcription.
AB  - Transcription of the H ferritin gene in vivo is stimulated by cAMP and repressed
      by the E1A oncoprotein. We report here the identification of the cis-element in
      the human promoter responsive to both cAMP- and E1A-mediated signals. This
      promoter region is included between positions -62 to -45 and binds a approximate
      120-kDa transcription factor called Bbf. Bbf forms a complex in vivo with the
      coactivator molecules p300 and CBP. Recombinant E1A protein reduces the formation
      of these complexes. In vivo overexpression of p300 in HeLa cells reverses the E1A
      mediated inhibition of the ferritin promoter transcription driven by Bbf. These
      data suggest the existence of a common mechanism for the cAMP activation and the
      E1A-mediated repression of H ferritin transcription.

PMID- 9252396
TI  - Regulation of protein kinase Cmu by basic peptides and heparin. Putative role of
      an acidic domain in the activation of the kinase.
AB  - Protein kinase Cmu is a novel member of the protein kinase C (PKC) family that
      differs from the other isoenzymes in structural and enzymatic properties. No
      substrate proteins of PKCmu have been identified as yet. Moreover, the regulation
      of PKCmu activity remains obscure, since a structural region corresponding to the
      pseudosubstrate domains of other PKC isoenzymes has not been found for PKCmu.
      Here we show that aldolase is phosphorylated by PKCmu in vitro. Phosphorylation
      of aldolase and of two substrate peptides by PKCmu is inhibited by various
      proteins and peptides, including typical PKC substrates such as histone H1,
      myelin basic protein, and p53. This inhibitory activity seems to depend on
      clusters of basic amino acids in the protein/peptide structures. Moreover, in
      contrast to other PKC isoenzymes PKCmu is activated by heparin and dextran
      sulfate. Maximal activation by heparin is about twice and that by dextran sulfate
      four times as effective as maximal activation by phosphatidylserine plus 12-O
      tetradecanoylphorbol-13-acetate, the conventional activators of c- and nPKC
      isoforms. We postulate that PKCmu contains an acidic domain, which is involved in
      the formation and stabilization of an active state and which, in the inactive
      enzyme, is blocked by an intramolecular interaction with a basic domain. This
      intramolecular block is thought to be released by heparin and possibly also by 12
      O-tetradecanoylphorbol-13-acetate/phosphatidylserine, whereas basic peptides and
      proteins inhibit PKCmu activity by binding to the acidic domain of the active
      enzyme.

PMID- 9252397
TI  - Sequence-specific and domain-specific DNA repair in xeroderma pigmentosum and
      Cockayne syndrome cells.
AB  - Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) cells have specific DNA
      repair defects. We had previously analyzed repair rates of cyclobutane pyrimidine
      dimers at nucleotide resolution along the human JUN gene in normal fibroblasts
      and found very efficient repair of sequences near the transcription initiation
      site but slow repair along the promoter. To investigate sequence-specific repair
      rate patterns in XP and CS cells, we conducted a similar analysis in XPA, XPB,
      XPC, XPD, and CSB fibroblasts. XPA cells were almost completely repair-deficient
      at all sequences analyzed. XPC cells repaired only the transcribed DNA strand
      beginning at position -20 relative to the transcription start site. Both XBP and
      XPD cells were deficient in repair of nontranscribed DNA and also very
      inefficiently repaired the transcribed strand including sequences near the
      transcription start site. CSB cells exhibited rapid repair near the transcription
      initiation site but were deficient in repair of sequences encountered by RNA
      polymerase during elongation (beginning at position +20). Since transcription of
      the JUN gene was UV-induced in all fibroblast strains, including CSB, the
      defective repair of the transcribed strand in CSB cannot be explained by a lack
      of transcription; rather, it appears to be a true DNA repair defect.

PMID- 9252398
TI  - Characterization of point mutations in patients with X-linked ichthyosis. Effects
      on the structure and function of the steroid sulfatase protein.
AB  - X-linked ichthyosis is the result of steroid sulfatase (STS) deficiency. While
      most affected individuals have extensive deletions of the STS gene, point
      mutations have been reported in three patients (1). In this study, we identify an
      additional three point mutations and characterize the effects of all six
      mutations on STS activity and expression. All six are unique single base pair
      substitutions. The mutations are located in a 105-amino acid region of the C
      terminal half of the polypeptide. Five of the six mutations involve the
      substitutions of Pro or Arg for Trp372, Arg for His444, Tyr for Cys446, or Leu
      for Cys341. The other mutation is in a splice junction and results in a
      frameshift causing premature termination of the polypeptide at residue 427. All
      the affected residues are conserved to some degree within the sulfatase family.
      The six mutations were reproduced in normal STS cDNA and transiently expressed in
      STS-deficient cells. All six mutant vectors direct the expression of STS protein
      that lacks enzymatic activity. The mutant polypeptides show a shift in mobility
      on SDS-PAGE and resistance to proteinase K digestion when translated in the
      presence of dog pancreas microsomes, indicating glycosylation and normal
      translocation.

PMID- 9252399
TI  - Phorbol ester down-regulation of lung surfactant protein B gene expression by
      cytoplasmic trapping of thyroid transcription factor-1 and hepatocyte nuclear
      factor 3.
AB  - The lung-specific surfactant protein B (SP-B) is essential for surfactant
      function and normal respiration. We investigated the role of thyroid
      transcription factor-1 (TTF-1) and hepatocyte nuclear factor 3 (HNF3) in the down
      regulation of SP-B gene expression by phorbol ester in pulmonary adenocarcinoma
      H441 cells. Responsiveness to 12-O-tetradecanoylphorbol-13-acetate (TPA)
      localized to the SP-B proximal promoter (-140/-65 bp) and specifically to binding
      sites for TTF-1 and HNF3, which act as cell-specific enhancers of SP-B
      expression. Treatment of cells with TPA (10 nM) caused a time-dependent decrease
      in both TTF-1 and HNF3 in nuclear extracts and accumulation of both factors in
      the cytoplasm as assessed by electromobility shift, Western, Southwestern, and
      immunofluorescence assays. Treatment did not alter the mRNA content or DNA
      binding activity for either transcription factor. We conclude that down
      regulation of SP-B gene expression by phorbol ester involves cytoplasmic trapping
      and loss of TTF-1 and HNF3 from the nucleus. This mechanism of action is
      independent of AP-1 and other transcription factors known to be influenced by
      phorbol ester.

PMID- 9252400
TI  - Streptococcal protein H forms soluble complement-activating complexes with IgG,
      but inhibits complement activation by IgG-coated targets.
AB  - Protein H, a surface protein of Streptococcus pyogenes interacting with the
      constant Fc region of IgG, is known to be released from the streptococcal surface
      by a cysteine proteinase produced by the bacteria. Poststreptococcal
      glomerulonephritis and rheumatic fever are conditions in which immune complexes
      and autoimmune mechanisms have been suggested to play pathogenetic roles. The
      present study demonstrates that addition of protein H to human serum produces
      complement activation with dose-dependent cleavage of C3. The activation was IgG
      dependent and the result of complexes formed between IgG and protein H. These
      complexes were size heterogeneous with molecular masses of 400 kDa to 1.4 MDa.
      Using complement-depleted serum reconstituted with complement proteins, the
      activation by protein H was found to be dependent of the classical, but
      independent of the alternative pathway of complement. In contrast to results of
      experiments based on soluble protein H.IgG complexes, complement activation was
      inhibited by protein H when IgG was immobilized on a surface. The interaction
      between C1q and immunoglobulins represents the first step in the activation of
      the classical pathway, and protein H efficiently inhibited the binding of C1q to
      IgG immobilized on polyacrylamide beads. Protein H reduced C3 deposition on the
      IgG-coated beads and inhibited immune hemolysis of IgG-sensitized erythrocytes.
      Finally, significantly less C3 was deposited on the surface of protein H
      expressing wild-type streptococci than on the surface of isogenic mutant bacteria
      devoid of protein H. The results demonstrate that protein H.IgG complexes
      released from the streptococcal surface can produce complement breakdown at the
      sites of infection, whereas complement activation on bacterial surfaces is
      inhibited. This should have important implications for host-parasite
      relationships. In addition, soluble protein H.IgG complexes might contribute to
      immunological complications of streptococcal infections.

PMID- 9252401
TI  - Cloning and functional expression of a new water channel abundantly expressed in
      the testis permeable to water, glycerol, and urea.
AB  - A new member of the aquaporin (AQP) family has been identified from rat testis.
      This gene, referred as aquaporin 7 (AQP7), encodes a 269-amino acid protein that
      contained the conserved NPA motifs of MIP family proteins. AQP7 has the amino
      acid sequence homology with other aquaporins ( approximately 30%), and it is
      highest with AQP3 (48%), suggesting that both AQP3 and AQP7 belong to a subfamily
      in the MIP family. Injection of AQP7-cRNA into Xenopus oocytes expressed a 26-kDa
      protein detected by immunoblotting. The expression of AQP7 in oocytes stimulated
      the osmotic water permeability by 10-fold which was not inhibited by 0.3 mM
      mercury chloride. The Arrhenius activation energy for the stimulated water
      permeability was low (2.1 kcal/mol). AQP7 also facilitated glycerol and urea
      transport by 5- and 9-fold, respectively. The activation energy for glycerol was
      also low (5.3 kcal/mol after the correction of the endogenous glycerol
      permeability of oocytes). Northern blot analysis revealed a 1.5-kilobase pair
      transcript expressed abundantly in testis. In situ hybridization of testis
      revealed the expression of AQP7 at late spermatids in seminiferous tubules. The
      immunohistochemistry of testis localized the AQP7 expression at late spermatids
      and at maturing sperms. AQP7 may play an important role in sperm function.

PMID- 9252402
TI  - A mitochondrial DNA primase from the trypanosomatid Crithidia fasciculata.
AB  - We have purified to near homogeneity a DNA primase from a mitochondrial fraction
      of the trypanosomatid Crithidia fasciculata. The enzyme is a single polypeptide
      chain of 28 kDa. Using a poly(dT) template and ATP as a substrate, the enzyme
      makes oligonucleotides of which the vast majority are about 10 nucleotides in
      size or smaller. With a single-stranded M13 DNA template and the four rNTPs as
      substrates, the enzyme makes heterogeneous oligonucleotides in the same size
      range. These oligonucleotides efficiently prime the synthesis of DNA by the
      Klenow DNA polymerase. Immunolocalization with antibodies against the purified
      enzyme confirms that the primase is mitochondrial. Furthermore, the enzyme
      localizes to specific regions of the cell's single mitochondrion, above and below
      the condensed kinetoplast DNA. The primase does not co-localize with the
      mitochondrial topoisomerase II and DNA polymerase beta, both of which are
      associated with two protein complexes positioned on opposite sides of the
      kinetoplast disc. These localization studies have significant implications for
      the mechanism of kinetoplast DNA replication.

PMID- 9252403
TI  - Membrane cofactor protein (CD46) is a basolateral protein that is not
      endocytosed. Importance of the tetrapeptide FTSL at the carboxyl terminus.
AB  - Membrane cofactor protein (MCP) is a widely distributed complement regulatory
      protein that is expressed on the basolateral surface of polarized epithelial
      cells. The basolateral targeting of the BC1 isoform of MCP was analyzed by
      generating deletion mutants and point mutants within the cytoplasmic tail of 16
      amino acids. A sequence of four amino acids, FTSL, was found to be indispensable
      for the basolateral transport of MCP. This tetrapeptide has two unique features
      compared with the targeting motifs of other basolateral proteins: (i) it contains
      a phenylalanine rather than a tyrosine at position 1; (ii) it is located at the
      very COOH-terminal end. Replacement of the phenylalanine or the leucine by an
      alanine resulted in a nonpolarized delivery to the cell surface. On the other
      hand, substitution of a tyrosine for the phenylalanine did not affect the
      basolateral transport of MCP. The latter mutant, however, was efficiently
      internalized, whereas the wild type protein was not subject to endocytosis. Our
      results indicate that the targeting signal YXX-large aliphatic that is involved
      in various sorting events has been modulated in MCP in such a way that it allows
      basolateral transport but not endocytosis.

PMID- 9252404
TI  - Cytosolic degradation of T-cell receptor alpha chains by the proteasome.
AB  - The T-cell antigen receptor (TCR) is an hetero-oligomeric membrane complex
      composed of at least seven transmembrane polypeptide chains that has served as a
      model for the assembly and degradation of integral membrane proteins in the
      endoplasmic reticulum (ER). Unassembled TCRalpha chains fail to mature to the
      Golgi apparatus and are rapidly degraded by a non-lysosomal "ER degradation"
      pathway that has been proposed to be autonomous to the ER. In these studies we
      show that the degradation of core-glycosylated TCRalpha is blocked by N-acetyl-L
      leucyl-L-leucyl-L-norleucinal (ALLN) and lactacystin, implicating the proteasome
      in ER degradation. Either acute or chronic treatment of TCRalpha-transfected
      cells with proteasome inhibitors cause the core-glycosylated TCRalpha chains to
      progressively shift to an approximately 28-kDa form that lacks N-linked
      oligosaccharides and the N-terminal signal peptide. The susceptibility of this 28
      kDa species to extravesicular protease indicates that it is not protected by the
      ER membrane and, hence, cytoplasmic. These data suggest a model in which TCRalpha
      chains that are translocated across the membrane, core-glycosylated, but fail to
      assemble are dislocated back to the cytoplasm for degradation by cytoplasmic
      proteasomes. Our data also suggest that covalent modification of TCRalpha with
      ubiquitin is not required for its degradation.

PMID- 9252405
TI  - Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by
      calmodulin.
AB  - The N-methyl-D-aspartate (NMDA) receptor plays important roles in synaptic
      plasticity and brain development. The NMDA receptor subunits have large
      intracellular domains in the COOH-terminal region that may interact with signal
      transducing proteins. By using the yeast two-hybrid system, we found that
      calmodulin interacts with the COOH terminus of the NR1 subunit and inactivates
      the channels in a Ca2+-dependent manner. Here we show that protein kinase C (PKC)
      mediated phosphorylation on serine residues of NR1 decreases its affinity for
      calmodulin. This suggests that PKC-mediated phosphorylation of NR1 prevents
      calmodulin from binding to the NR1 subunit and thereby inhibits the inactivation
      of NMDA receptors by calmodulin. In addition, we show that stimulation of
      metabotropic glutamate receptor 1alpha, which potentiates NMDA channels through
      PKC, decreases the ability of NR1 to bind to calmodulin. Thus, our data provide
      clues to understanding the basis of cross-talk between two types of receptors,
      metabotropic glutamate receptors and the NR1 subunit, in NMDA channel
      potentiation.

PMID- 9252406
TI  - Association of the multisubstrate docking protein Gab1 with the hepatocyte growth
      factor receptor requires a functional Grb2 binding site involving tyrosine 1356.
AB  - Hepatocyte growth factor/scatter factor is a multifunctional factor that induces
      mitogenesis, motility, invasion, and branching tubulogenesis of several
      epithelial and endothelial cell lines in culture. The receptor for hepatocyte
      growth factor has been identified as the Met-tyrosine kinase. Upon stimulation
      with hepatocyte growth factor, the Met beta subunit becomes highly phosphorylated
      on tyrosine residues, one of which, tyrosine 1356 within the carboxyl terminus,
      is crucial for dissociation, motility, and branching tubule formation in Madin
      Darby canine kidney epithelial cells. Tyrosine 1356 forms a multisubstrate
      binding site for the Grb2 and Shc adaptor proteins, the p85 subunit of
      phosphatidylinositol 3'-kinase, phospholipase Cgamma, and a phosphatase, SHP2. To
      investigate additional signaling molecules that are activated by the Met
      receptor, we have identified hepatocyte growth factor-induced phosphoproteins in
      tubular epithelial cells. We have established that proteins of 100-130 kDa are
      highly phosphorylated following stimulation of epithelial cells and that one of
      these is the Grb2-associated binding protein Gab1, a possible insulin receptor
      substrate-1-like signal transducer. We show that Gab1 is the major substrate for
      the Met kinase in vitro and in vivo. Association of Gab1 with Met requires a
      functional Grb2 binding site involving tyrosine 1356 and to a lesser extent
      tyrosine 1349. Met receptor mutants that fail to induce branching tubulogenesis
      are impaired in their ability to interact with Gab1, suggesting that Gab1 may
      play a role in these processes.

PMID- 9252407
TI  - Binding of polyamines to an autonomous domain of the regulatory subunit of
      protein kinase CK2 induces a conformational change in the holoenzyme. A proposed
      role for the kinase stimulation.
AB  - The means by which the cell regulates protein kinase CK2 remain obscure. However,
      natural polyamines, cellular compounds required for cell proliferation, have been
      reported to strongly stimulate CK2-mediated phosphorylation of a number of
      substrates. Using spermine analogs, we have shown that polyamines directly
      interact with the CK2 beta subunit, and the chemical features of the highly
      acidic binding site (Asp51-Tyr80) have been determined. In the present study, we
      show that the isolated beta subunit region extending from residue Asp51 to Pro110
      exhibits a specific and efficient polyamine binding activity similar to that of
      the entire beta subunit. Moreover, the replacement of Glu60, Glu61, and Glu63 of
      the beta subunit by 3 alanine residues leads to a loss of the spermine-induced
      stimulation of CK2 activity which correlates with a decrease in spermine binding
      affinity. Thermal stability studies indicate that the binding of spermine induces
      a 4 degrees C decrease of the Tm value for the holoenzyme. This was confirmed by
      circular dichroism analyses, which show that the 6 degrees C negative shift of
      the CK2 Tm value provoked by spermine binding, reflects a conformational change
      in the kinase. Together, these observations strongly suggest that this newly
      defined polyamine-binding domain is involved in the intrasteric regulation of CK2
      activity.

PMID- 9252408
TI  - Functional protein prenylation is required for the brefeldin A-dependent
      retrograde transport from the Golgi apparatus to the endoplasmic reticulum.
AB  - In cells exposed to brefeldin A (BFA), enzymes of the Golgi apparatus are
      redistributed to the endoplasmic reticulum (ER) by retrograde membrane flow,
      where they may cause modifications on resident ER proteins. We have used a
      truncated form of the rough ER-specific type I transmembrane glycoprotein
      ribophorin I as a probe to detect Golgi glycosyltransferases relocated to the ER
      in a BFA-dependent fashion. This polypeptide (RI332) comprises the 332 amino
      terminal amino acids of ribophorin I and behaves like a luminal ER protein when
      expressed in HeLa cells. Upon treatment of the cells with BFA, RI332 becomes
      quantitatively O-glycosylated by Golgi glycosyltransferases that are transported
      back to the ER. Here we demonstrate that pretreatment of the cells with
      lovastatin, an inhibitor of HMG-CoA reductase, abrogates this modification and
      that mevalonate, the product formed in the step inhibited by the drug, is able to
      counteract the effect of lovastatin. We also show by immunofluorescence using
      mannosidase II as a Golgi marker that the BFA-induced retrograde transport of
      Golgi enzymes is blocked by lovastatin, although electron microscopy indicates
      that BFA causes disassembly of the Golgi apparatus into swollen vesicles and
      tubules. Our observations support the role of a prenylated protein, such as the
      geranylgeranylated small G protein Rab6, in the retrograde transport from the
      Golgi apparatus to the ER, since lovastatin acts by inhibiting its prenylation.

PMID- 9252409
TI  - Chromogranin A fragments modulate cell adhesion. Identification and
      characterization of a pro-adhesive domain.
AB  - Although several functions have been suggested for chromogranin A, a glycoprotein
      secreted by many neuroendocrine cells, the physiological role of this protein and
      of its proteolytic fragments has not been established. We have found that
      mixtures of chromogranin A fragments can inhibit fibroblast adhesion. The anti
      adhesive activity was converted into pro-adhesive activity by limited trypsin
      treatment. Pro-adhesive effects were observed also with recombinant N-terminal
      fragments corresponding to residues 1-78 and 1-115 and with a synthetic peptide
      encompassing the residues 7-57. These fragments induced adhesion and spreading of
      fibroblasts on plates coated with collagen I or IV, laminin, fetal calf serum
      (FCS) but not on bovine serum albumin. The long incubation time required for
      adhesion assays (4 h) and the FCS requirements for optimal adhesion suggest that
      the adhesive activity is likely indirect and requires other proteins present in
      the FCS or made by the cells. These findings suggest that chromogranin A and its
      fragments could play a role in the regulation of cell adhesion. Since
      chromogranin A is concentrated and stored within granules and rapidly released by
      neuroendocrine cells and neurons after an appropriate stimulus, this protein
      could be important for the local control of cell adhesion by stimulated cells.

PMID- 9252410
TI  - Stimulus-dependent phosphorylation of G-protein-coupled receptors by casein
      kinase 1alpha.
AB  - We have previously demonstrated that the phospholipase C-coupled m3-muscarinic
      receptor is phosphorylated in an agonist-sensitive manner by a protein kinase of
      approximately 40 kDa purified from porcine cerebellum (Tobin, A. B., Keys, B.,
      and Nahorski, S. R. (1996) J. Biol Chem. 271, 3907-3916). This kinase, called
      muscarinic receptor kinase (MRK), is distinct from second messenger-regulated
      protein kinases and from beta-adrenergic receptor kinase and other members of the
      G-protein-coupled receptor kinase family. In the present study we propose that
      MRK is casein kinase 1alpha (CK1alpha) based on the following evidence: 1) the
      amino acid sequence from two proteolytic peptide fragments derived from purified
      MRK corresponded exactly to sequences within CK1alpha. 2) Casein kinase activity
      co-eluted with MRK activity from the final two chromatography steps in the
      purification of porcine brain MRK. 3) Recombinant CK1alpha expressed in Sf9 cells
      is able to phosphorylate both casein and the bacterial fusion protein, Ex-m3,
      that contains a portion of the third intracellular loop of the m3-muscarinic
      receptor downstream of glutathione S-transferase. 4) Partially purified CK1alpha
      increased the level of muscarinic receptor phosphorylation in an agonist
      sensitive manner when reconstituted with membranes from Chinese hamster ovary-m3
      cells expressing the human recombinant m3-muscarinic receptor. 5) Partially
      purified CK1alpha phosphorylated rhodopsin, contained in urea-treated bovine rod
      outer segment membranes, and the extent of phosphorylation was increased in the
      presence of light. These data demonstrate that the kinase previously called MRK
      is CK1alpha, and that CK1alpha offers an alternative protein kinase pathway from
      that of the G-protein-coupled receptor kinase family for the stimulus-dependent
      phosphorylation of the m3-muscarinic receptor, rhodopsin, and possibly other G
      protein-coupled receptors.

PMID- 9252411
TI  - Cis-elements required for the demethylation of the mouse M-lysozyme downstream
      enhancer.
AB  - The mouse lysozyme downstream enhancer was previously colocalized with the DNase
      I-hypersensitive site in the chromatin of mature macrophages. This hypersensitive
      site was shown to be macrophage differentiation-dependent. Demethylation of CpG
      sequences within the enhancer is correlated with lysozyme expression in mature
      macrophages. Binding of the GABP heterotetrameric transcription factor to the
      enhancer core element (MLDE), only seen in vivo on the demethylated MLDE element
      in macrophages, is inhibited by DNA methylation. Here, we analyzed the DNA
      sequences required for demethylation. In electrophoretic mobility shift
      experiments we found that in addition to the complete methylated MLDE the
      hemimethylated form of the lower strand inhibits GABP binding as well. Therefore,
      GABP is unlikely to be the mediator of demethylation. In addition, we show by
      stable DNA transfections of methylated mouse lysozyme enhancer sequences that
      MLDE-flanking sequences are required for demethylation. We narrowed down these
      DNA elements to two short regions of 163 and 79 base pairs on either side of the
      MLDE, each of which is sufficient to mediate demethylation of the GABP site.

PMID- 9252412
TI  - Ca2+/calmodulin causes Rab3A to dissociate from synaptic membranes.
AB  - The GTPase Rab3A has been postulated to cycle on and off synaptic membranes
      during the course of neurotransmission. Moreover, a Rab guanine nucleotide
      dissociation inhibitor has been shown to cause Rab3A to dissociate from synaptic
      membranes in vitro. We demonstrate here that Ca2+/calmodulin also can cause Rab3A
      to dissociate from synaptic membranes in vitro. Like Rab guanine nucleotide
      dissociation inhibitor, it forms a 1:1 complex with Rab3A that requires both the
      lipidated C terminus of Rab3A and the presence of bound guanine nucleotide. In
      addition, a synthetic peptide corresponding to the Lys62-Arg85 sequence of Rab3A
      can prevent the dissociating effect of each protein and disrupt complexes between
      each protein and Rab3A. However, Ca2+/calmodulin's effect differs from that of
      Rab guanine nucleotide dissociation inhibitor not only in being Ca2+-dependent
      but also in having a less stringent requirement for GDP as opposed to GTP and in
      involving a less complete dissociation of Rab3A. The functional significance in
      vivo of Ca2+/calmodulin's effect remains to be determined; it may depend in part
      on the relative amounts of Ca2+/calmodulin and Rab guanine nucleotide
      dissociation inhibitor that are available for binding to Rab3A in individual,
      activated nerve termini.

PMID- 9252413
TI  - Isoform-specific interaction of the myosin-binding proteins (MyBPs) with skeletal
      and cardiac myosin is a property of the C-terminal immunoglobulin domain.
AB  - Full-length cDNAs encoding chicken and human skeletal MyBP-H and MyBP-C have been
      isolated and sequenced (1-5). All are members of a protein family with repetitive
      immunoglobulin C2 and fibronectin type III motifs. The myosin binding domain was
      mapped to a single immunoglobulin motif in cardiac MyBP-C and skeletal MyBP-H.
      Limited alpha-chymotryptic digestion of cardiac MyBP-C generated three peptides,
      similar in relative mobility to those of skeletal MyBP-C: approximately 100, 40,
      and 15 kDa. Tryptic digestion of MyBP-H yielded two peptides: approximately 50
      and 14 kDa. Partial amino acid sequences proved that the 15- and 14-kDa fragments
      are located at the C termini of cardiac MyBP-C and skeletal MyBP-H, respectively.
      Only the 14- and 15-kDa peptides bound to myosin. Thus, the myosin binding site
      in all three proteins resides within an homologous, C-terminal immunoglobulin
      domain. Binding reactions (2) between the skeletal and cardiac MyBPs and
      corresponding myosin isoforms demonstrated saturable binding of the MyBP proteins
      and their C-terminal peptides to myosin, but there are higher limiting
      stoichiometries with the homologous isoform partners. Evidence is presented
      indicating that MyBP-H and -C compete for binding to a discrete number of sites
      in myosin filaments.

PMID- 9252414
TI  - Role of the yeast phosphatidylinositol/phosphatidylcholine transfer protein
      (Sec14p) in phosphatidylcholine turnover and INO1 regulation.
AB  - In yeast, mutations in the CDP-choline pathway for phosphatidylcholine
      biosynthesis permit the cell to grow even when the SEC14 gene is completely
      deleted (Cleves, A., McGee, T., Whitters, E., Champion, K., Aitken, J., Dowhan,
      W., Goebl, M., and Bankaitis, V. (1991) Cell 64, 789-800). We report that strains
      carrying mutations in the CDP-choline pathway, such as cki1, exhibit a choline
      excretion phenotype due to production of choline during normal turnover of
      phosphatidylcholine. Cells carrying cki1 in combination with sec14(ts), a
      temperature-sensitive allele in the gene encoding the
      phosphatidylinositol/phosphatidylcholine transporter, have a dramatically
      increased choline excretion phenotype when grown at the sec14(ts)-restrictive
      temperature. We show that the increased choline excretion in sec14(ts) cki1 cells
      is due to increased turnover of phosphatidylcholine via a mechanism consistent
      with phospholipase D-mediated turnover. We propose that the elevated rate of
      phosphatidylcholine turnover in sec14(ts) cki1 cells provides the metabolic
      condition that permits the secretory pathway to function when Sec14p is
      inactivated. As phosphatidylcholine turnover increases in sec14(ts) cki1 cells
      shifted to the restrictive temperature, the INO1 gene (encoding inositol-1
      phosphate synthase) is also derepressed, leading to an inositol excretion
      phenotype (Opi-). Misregulation of the INO1 gene has been observed in many
      strains with altered phospholipid metabolism, and the relationship between
      phosphatidylcholine turnover and regulation of INO1 and other co-regulated genes
      of phospholipid biosynthesis is discussed.

PMID- 9252415
TI  - Interaction of earthworm hemolysin with lipid membranes requires sphingolipids.
AB  - Lytic activity in the coelomic fluid of earthworm (Eisenia fetida fetida) has
      been ascribed to eiseniapore, a hemolytic protein of 38 kDa. Since receptors for
      eiseniapore on target cell membranes are not known, we used lipid vesicles of
      various composition to determine whether specific lipids may serve as receptors.
      Lytic activity of eiseniapore was probed by the relief of fluorescence
      dequenching from the fluorophore 8-aminonaphthalene-1,3, 6-trisulfonic acid
      originally incorporated into the vesicle lumen as a complex with p-xylene-bis
      pyridinium bromide. Hemolysin binds to and disturbs the lipid bilayer only when
      distinct sphingolipids consisting of a hydrophilic head group as
      phosphorylcholine or galactosyl as well as the ceramide backbone, e.g.
      sphingomyelin, are present. Cholesterol enhances eiseniapore lytic activity
      toward sphingomyelin-containing vesicles probably due to interaction with
      sphingomyelin. Leakage of vesicles was most efficient when the lipid composition
      resembled that of the outer leaflet of human erythrocytes. Presumably, an
      oligomeric protein pore formed by six monomers is responsible for leakage of
      sphingomyelin-containing vesicles. The secondary structure of eiseniapore did not
      change upon binding to lipid membranes. The lytic activity of eiseniapore was
      completely abolished after its denaturation or after preincubation with
      polyclonal antibodies. Our results suggest that the presence of specific
      sphingolipids is sufficient to mediate lytic activity of eiseniapore. This action
      contributes to our understanding of earthworm immune responses.

PMID- 9252416
TI  - Parental chromosome-specific chromatin conformation in the imprinted U2af1-rs1
      gene in the mouse.
AB  - The imprinted U2af1-rs1 gene on mouse chromosome 11 is expressed exclusively from
      the paternal allele. We found that U2af1-rs1 resides in a chromosomal domain that
      displays marked differences in chromatin conformation and DNA methylation between
      the parental chromosomes. Chromatin conformation was assayed in brain and liver,
      in fetuses, and in embryonic stem cells by sensitivity to nucleases in nuclei. In
      all these tissues, the unmethylated paternal chromosome is sensitive to DNase-I
      and MspI and has two DNase-I hypersensitive sites in the 5'-untranslated region.
      In brain and in differentiated stem cells, which display high levels of U2af1-rs1
      expression, a paternal DNase-I hypersensitive site is also readily apparent in
      the promoter region. On the maternal chromosome, in contrast, the entire U2af1
      rs1 gene and its promoter are highly resistant to DNase-I and MspI in all tissues
      analyzed and are fully methylated. No differential MNase sensitivity was detected
      in this imprinted domain. The parental chromosome-specific DNA methylation and
      chromatin conformation were also present in parthenogenetic and androgenetic
      cells and in tissues from animals maternally or paternally disomic for chromosome
      11. This demonstrates that these parental chromosome-specific epigenotypes are
      independently established and maintained and provides no evidence for
      interallelic trans-sensing and counting mechanisms in U2af1-rs1.

PMID- 9252417
TI  - The mitochondrial hsp70 chaperone system. Effect of adenine nucleotides, peptide
      substrate, and mGrpE on the oligomeric state of mhsp70.
AB  - Mitochondrial hsp70 (mhsp70) is a key component in the import and folding of
      mitochondrial proteins. In both processes, mhsp70 cooperates with the
      mitochondrial nucleotide exchange factor mGrpE (also termed Mge1p). In this work
      we have characterized the self-association of purified mhsp70, the interaction of
      mhsp70 with isolated mGrpE and protein substrate, and the effect of nucleotides
      on these interactions. mhsp70 can form oligomers that are dissociated by ATP or
      by a nonhydrolyzable ATP analog. A substrate peptide binds to mhsp70 in the
      absence of added nucleotides and is released by ATP but not by ADP. Binding of
      the peptide causes nucleotide-independent dissociation of the mhsp70 oligomers
      and enhances the mhsp70 ATPase. Purified mGrpE forms a homodimer. In the absence
      of added nucleotides, one mGrpE dimer binds to one molecule of mhsp70, forming a
      stable 122 kDa hetero-oligomer. This complex is weakened by ADP and completely
      dissociated by ATP.

PMID- 9252418
TI  - Induction of IgE antibody responses by glutathione S-transferase from the German
      cockroach (Blattella germanica).
AB  - We report that a major 23-kDa allergen from German cockroach (Blattella
      germanica) is a glutathione S-transferase (EC 2.5.1.18; GST). Natural B.
      germanica GST, purified from cockroach body extracts by glutathione affinity
      chromatography, and recombinant protein expressed in Escherichia coli using the
      pET21a vector, showed excellent IgE antibody binding activity. B. germanica GST
      caused positive immediate skin tests in cockroach-allergic patients using as
      little as 3 pg of recombinant protein. The NH2-terminal sequence of the natural
      protein and the deduced amino acid sequence from cDNA were identical except for
      one substitution (Phe9 --> Cys). Assignment of this protein to the GST
      superfamily was based on binding to glutathione and sequence identity (42-51%) to
      the GST-2 subfamily from insects, including Anopheles gambiae and Drosophila
      melanogaster. B. germanica GST contained 18 of the 26 invariable residues
      identified in mammalian GST by x-ray crystallography and exhibited enzymic
      activity against a GST substrate. Our results show that cockroach GST causes IgE
      antibody responses and is associated with asthma. The data strongly support the
      view that the immune response to GST plays an important role in allergic
      diseases.

PMID- 9252419
TI  - Localization of the iodomycin binding site in hamster P-glycoprotein.
AB  - P-glycoprotein, the overexpression of which is a major cause for the failure of
      cancer chemotherapy in man, recognizes and transports a broad range of
      structurally unrelated amphiphilic compounds. This study reports on the
      localization of the binding site of P-glycoprotein for iodomycin, the Bolton
      Hunter derivative of the anthracycline daunomycin. Plasma membrane vesicles
      isolated from multidrug-resistant Chinese hamster ovary B30 cells were
      photolabeled with [125I]iodomycin. After chemical cleavage behind the tryptophan
      residues, 125I-labeled peptides were separated by electrophoresis and high
      performance liquid chromatography. Edman sequencing revealed that [125I]iodomycin
      had been predominantly incorporated into the fragment 230-312 of isoform I of
      hamster P-glycoprotein. According to models based on hydropathy plots, the amino
      acid sequence 230-312 forms the distal part of transmembrane segment 4, the
      second cytoplasmic loop, and the proximal part of transmembrane segment 5 in the
      N-terminal half of P-glycoprotein. The binding site for iodomycin is recognized
      with high affinity by vinblastine and cyclosporin A.

PMID- 9252420
TI  - Effect of disulfide bonds of transcobalamin II receptor on its activity and
      basolateral targeting in human intestinal epithelial Caco-2 cells.
AB  - Transcobalamin II-receptor (TC II-R) contains 10 half-cysteines, of which 8 are
      involved in intramolecular disulfide bonding. Reduction followed by alkylation
      with N-ethylmaleimide (NEM) of the 62-kDa TC II-R monomer in vitro or treatment
      of human intestinal epithelial Caco-2 cells with low concentrations (10(-6) M) of
      NEM resulted in TC II-R exhibiting a loss of ligand binding and an increase in
      its apparent molecular mass by 10 kDa to 72 kDa. Domain-specific biotinylation
      studies using NEM-treated filter-grown cells revealed loss of TC II-R but not
      cation-independent mannose 6-phosphate receptor protein at the basolateral cell
      surface. Pulse-chase labeling of NEM-treated cells with [35S]methionine revealed
      that the modified 72-kDa TC II-R, like the native 62-kDa TC II-R in untreated
      cells, turned over rapidly with a t1/2 of 7.5 h and was sensitive to treatment
      with peptide N-glycosidase F, sialidase alone, or sialidase and O-glycanase but
      not to treatment with endoglycosidase H. Labeled 72-kDa TC II-R, which was
      retained intracellularly following treatment of Caco-2 cells with methyl
      methanethiosulfonate, returned to the basolateral cell surface following
      withdrawal of cells from methyl methanethiosulfonate treatment and exposure to
      dithiothreitol. Based on these results, we suggest that formation and maintenance
      of intramolecular disulfide bonds of TC II-R is important for its acquisition of
      ligand binding and post-trans-Golgi trafficking to basolateral surface membranes
      but not for its turnover and exit from the endoplasmic reticulum or trafficking
      through the Golgi.

PMID- 9252421
TI  - Dimerization of the highly conserved light chain shared by dynein and myosin V.
AB  - The Mr 8,000 light chain originally identified in Chlamydomonas flagellar dynein
      is also a component of both cytoplasmic dynein and myosin V. Furthermore, this
      small protein has been implicated as an inhibitor of neuronal nitric oxide
      synthase, suggesting that it may play multiple regulatory roles within the cell.
      Covalent cross-linking of both dynein and myosin V using 1,5-difluoro-2, 4
      dinitrobenzene revealed that this light chain exists as a dimer in situ. This
      observation was confirmed using two additional amine-selective cross-linking
      reagents (dimethyl pimelimidate and disuccinimidyl suberate). When expressed as a
      C-terminal fusion with maltose-binding protein, the presence of the light chain
      caused the recombinant molecule to dimerize. Analysis of fusions containing
      truncated light chains identified the predicted amphiphilic helix (residues 14
      32) as sufficient to cause dimerization; cross-linking required a second helical
      segment (residues 33-46). Together the data presented suggest that two light
      chains interact to form a parallel dimeric structure. This arrangement has
      significant implications for the potential functions of this highly conserved
      molecule and suggests a mechanism by which it might dissociate nitric oxide
      synthase.

PMID- 9252422
TI  - The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the
      activation of the transcription factor insulin upstream factor 1 and insulin gene
      transcription by high glucose in pancreatic beta-cells.
AB  - Insulin upstream factor 1 (IUF1), a transcription factor present in pancreatic
      beta-cells, binds to the sequence C(C/T)TAATG present at several sites within the
      human insulin promoter. Here we isolated and sequenced cDNA encoding human IUF1
      and exploited it to identify the signal transduction pathway by which glucose
      triggers its activation. In human islets, or in the mouse beta-cell line MIN6,
      high glucose induced the binding of IUF1 to DNA, an effect mimicked by
      serine/threonine phosphatase inhibitors, indicating that DNA binding was induced
      by a phosphorylation mechanism. The glucose-stimulated binding of IUF1 to DNA and
      IUF1-dependent gene transcription were both prevented by SB 203580, a specific
      inhibitor of stress-activated protein kinase 2 (SAPK2, also termed p38 mitogen
      activated protein kinase, reactivating kinase, CSBP, and Mxi2) but not by several
      other protein kinase inhibitors. Consistent with this finding, high glucose
      activated mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP
      kinase-2) (a downstream target of SAPK2) in MIN6 cells, an effect that was also
      blocked by SB 203580. Cellular stresses that trigger the activation of SAPK2 and
      MAPKAP kinase-2 (arsenite, heat shock) also stimulated IUF1 binding to DNA and
      IUF1-dependent gene transcription, and these effects were also prevented by SB
      203580. IUF1 expressed in Escherichia coli was unable to bind to DNA, but binding
      was induced by incubation with MgATP, SAPK2, and a MIN6 cell extract, which
      resulted in the conversion of IUF1 to a slower migrating form. SAPK2 could not be
      replaced by p42 MAP kinase, MAPKAP kinase-2, or MAPKAP kinase-3. The glucose
      stimulated activation of IUF1 DNA binding and MAPKAP kinase-2 (but not the
      arsenite-induced activation of these proteins) was prevented by wortmannin and LY
      294002 at concentrations similar to those that inhibit phosphatidylinositide 3
      kinase. Our results indicate that high glucose (a cellular stress) activates
      SAPK2 by a novel mechanism in which a wortmannin/LY 294002-sensitive component
      plays an essential role. SAPK2 then activates IUF1 indirectly by activating a
      novel IUF1-activating enzyme.

PMID- 9252423
TI  - The role of the cystine loop in acetylcholine receptor assembly.
AB  - Nicotinic acetylcholine receptors (AChRs) are composed of alpha, beta, gamma, and
      delta subunits, assembled into alpha2betagammadelta pentamers. A highly conserved
      feature of ionotropic neurotransmitter receptors, such as AChRs, is a 15-amino
      acid cystine "loop." We find that an intact cystine loop is necessary for
      complete AChR assembly. By preventing formation of the loop with 5 mM
      dithiothreitol, AChR subunits assemble into alphabetagamma trimers, but the
      subsequent steps in assembly are blocked. When alpha subunit loop cysteines are
      mutated to serines, assembly is blocked at the same step as with dithiothreitol.
      In contrast, when beta subunit loop cysteines are mutated to serines, assembly is
      blocked at a later step, i.e. after assembly of alphabetagammadelta tetramers and
      before the addition of the second alpha subunit. After formation of the cystine
      loop, the alpha subunit undergoes a conformational change, which buries the loop.
      This conformational change is concurrent with the step in assembly blocked by
      removal of the disulfide bond of the cystine loop, i.e. after assembly of
      alphabetagamma trimers and before the addition of the delta subunit. The data
      indicate that the alpha subunit conformational change involving the cystine loop
      is key to a series of folding events that allow the addition of unassembled
      subunits.

PMID- 9252424
TI  - Promoter-dependent synergy between glucocorticoid receptor and Stat5 in the
      activation of beta-casein gene transcription.
AB  - Steroid hormone receptors and Stat factors comprise two distinct families of
      inducible transcription factors. Activation of a member of each family, namely
      the glucocorticoid receptor by glucocorticoids and Stat5 by prolactin, is
      required for the efficient induction of the expression of milk protein genes in
      the mammary epithelium. We have studied the mode of interaction between Stat5 and
      the glucocorticoid receptor in the activation of beta-casein gene transcription.
      The functional role of potential half-palindromic glucocorticoid receptor-binding
      sites mapped previously in the promoter region was investigated. beta-Casein gene
      promoter chloramphenicol acetyltransferase constructs containing mutations and
      deletions in these sites were tested for their responsiveness to the synergistic
      effect of prolactin and dexamethasone employing COS-7 cells or HC11 mammary
      epithelial cells. Synergism depended on promoter regions containing intact
      binding sites for the glucocorticoid receptor and Stat5. The carboxyl-terminal
      transactivation domains of Stat5a and Stat5b were not required for this
      synergism. Our results suggest that in lactogenic hormone response elements
      glucocorticoid receptor molecules bound to nonclassical half-palindromic sites
      gain competence as transcriptional activators by the interaction with Stat5
      molecules binding to vicinal sites.

PMID- 9252425
TI  - Effects of pediatric cancer therapy on the musculoskeletal system.
AB  - This review discusses the effects of treatment of pediatric malignancies on the
      musculoskeletal system with an emphasis on plain radiographic and MR imaging
      findings following radiation therapy, chemotherapy, bone marrow transplantation
      and hematopoietic growth factor administration.

PMID- 9252427
TI  - Bronchopulmonary dysplasia: correlation of radiographic and clinical findings.
AB  - BACKGROUND AND PURPOSE: Abnormalities of the chest wall have been described in
      bronchopulmonary dysplasia (BPD). Clinical, radiographic and pulmonary function
      variables were evaluated in 1-year-old children ventilated because of neonatal
      lung disease in order to quantify these thoracic changes and to evaluate the lung
      disease. METHODS: The pulmonary status of 51 infants with neonatal lung disease
      requiring artificial ventilation was reevaluated clinically and radiographically
      at the age of 1 year. Twenty-two of these infants had developed BPD. Thoracic
      depth and width were measured clinically and on chest X-ray. The Toce score
      evaluated the presence of cardiomegaly, hyperinflation, emphysema and
      interstitial lung disease. Lung function was measured after sedation using
      previously reported methods. In BPD patients, Toce score and lung function were
      determined and compared at 1 month and at 1 year of age. RESULTS: In BPD
      patients, chest depth was significantly smaller when measured clinically as well
      as on chest radiograph (P < 0.05; Mann-Whitney U-test). There was a statistically
      significant correlation between chest depth measured clinically and on chest X
      ray. Toce score was significantly higher in BPD patients (P < 0.05). In BPD
      patients intersitial abnormalities and decreased lung compliance were more
      frequent at the age of 1 month than at the age of 1 year. At the age of 1 year,
      hyperinflation was more frequent and at that time increased airway resistance was
      still noted. Thus the type of X-ray abnormality reflects the type of lung
      function disturbance. CONCLUSION: The flatness of the chest is most likely a
      consequence of the long-standing lung function abnormalities.

PMID- 9252426
TI  - Acute chest syndrome of sickle cell disease: radiographic and clinical analysis
      of 70 cases.
AB  - BACKGROUND: Acute chest syndrome (ACS) is a pulmonary illness with fever, chest
      pain, leukocytosis and new pulmonary opacity in a patient with sickle cell
      disease. It is a common reason for hospitalization in sickle cell patients, and a
      significant cause of mortality. The etiology of ACS is unclear. Lung or bone
      infarction and infection, among other possible causes, have been proposed.
      OBJECTIVE: We reviewed the chest radiographs and medical records of 41 patients
      with 70 episodes of ACS and correlated the clinical and radiographic courses in
      an attempt to better characterize and understand the syndrome. RESULTS: In 87 %
      of episodes, no identifiable etiology of ACS was found. This group of patients
      had a median age of 14 years and showed dramatic clinical and radiographic
      improvement within 24 h of therapy. In the remainder of episodes (13 %), an
      identifiable etiology was found, usually bacterial pneumonia. These patients were
      younger than the group without an identifiable etiology (median age 2 years) and
      had a prolonged radiographic course of illness. CONCLUSION: The chest radiographs
      of children with ACS without an identifiable etiology have an extremely typical
      appearance and evolution. Only in cases which do not have this typical pattern
      should infection be suspected as the underlying cause.

PMID- 9252428
TI  - The appearance of inverted Meckel diverticulum with intussusception on air enema.
AB  - This paper presents the appearances of inverted Meckel diverticulum with an
      irreducible intussusception on air enema in four children. The inverted Meckel
      diverticulum appeared as a bulbous (3) or triangular (1) filling defect in the
      air column projecting off the distal end of the soft tissue mass of the
      irreducible intussusceptum. The bulbous defect appears to be highly suggestive,
      and may be specific, for inverted Meckel diverticulum. Earlier recognition of the
      presence of the Meckel diverticulum as the lead point of the intussusception
      could have changed the management in two of the children.

PMID- 9252429
TI  - Pitfall: anomalous umbilical vein and absent ductus venosus in association with
      right congenital diaphragmatic hernia.
AB  - Congenital abnormalities of the umbilical venous system are rare. A case of fatal
      right congenital diaphragmatic hernia (CDH) in association with an anomalous
      umbilical vein bypassing the liver and directly entering the right atrium is
      presented. The ductus venosus was absent. Although much of the liver was within
      the right hemithorax, radiographs showed an apparently normal umbilical venous
      catheter (UVC) course, suggesting a normally positioned liver and mitigating
      against the diagnosis of CDH. Aberrant umbilical drainage, yielding a falsely
      normal appearing UVC course, may delay the diagnosis of CDH.

PMID- 9252430
TI  - Local physeal widening on MR imaging: an incidental finding suggesting prior
      metaphyseal insult.
AB  - OBJECTIVE: To offer a descriptive review which characterizes and evaluates the
      significance of local physeal widening, (cartilaginous signal extending from the
      physis into the adjacent metaphysis), identified on magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: MR images (recollected from exams performed
      between 1988 and 1995) of 31 metaphyses in 22 children where we recognized local
      physeal widening were examined retrospectively. These areas of physeal widening
      were evaluated for morphology, depth, location, signal intensity, and the
      coexistence of epiphyseal alterations. The characteristics of the signal
      abnormalities were correlated with the duration and type of any identifiable
      insult to the adjacent metaphysis, and with the development of growth
      disturbance. RESULTS: Twenty-six metaphyses had identifiable insults (19 single
      event and 7 sustained or repetitive). The widened physes were of focal tongue (n
      = 15), broad band (n = 10), or mixed (n = 6) morphology. Most (n = 27) areas of
      widening were isointense with the physeal cartilage on all sequences. Subsequent
      growth disturbance was more likely when the metaphyseal insult was a single event
      rather than sustained or repetitive (P = 0.023), with focal tongues (P = 0.029),
      and with centrally located lesions (P = 0.030). In five cases, the adjacent
      epiphysis showed signal abnormalities; all developed growth disturbance.
      Histologic examinations available in two limbs confirmed that the MR findings
      represented extensions of hypertrophic physeal chondrocytes into the metaphysis.
      CONCLUSION: Incidentally observed local physeal widening in a growing bone may
      represent the imprint of a previous or ongoing interference with endochondral
      ossification from a prior metaphyseal insult, rather than a primary metaphyseal
      disorder. Single event insults, physeal widening of focal tongue morphology,
      central distribution in the metaphysis, and concomitant epiphyseal signal
      abnormalities on MR imaging are significant predictors of subsequent growth
      disturbance.

PMID- 9252431
TI  - Interobserver variation in the sonographic estimation of renal volume in
      children.
AB  - OBJECTIVE: To quantify the interobserver variability in the sonographic
      estimation of renal volume in children. MATERIALS AND METHODS: Three observer
      pairs measured the lengths and diameters of 176 kidneys in 90 children. Renal
      volumes were estimated from the formula for a prolate ellipsoid. The mean and
      standard deviation of the absolute and percentage differences between observers
      were calculated. The 95 % limits of agreement for each pair of observers were
      derived. Log-transformed data were used to derive overall limits of agreement.
      RESULTS: Absolute interobserver variation increased with renal volume. Percentage
      variation was independent of renal size. There is a 95 % probability that a
      measurement of renal volume by one observer will be between 0.69 and 1.44 times a
      measurement made by a different observer. CONCLUSION: The interobserver variation
      in the sonographic estimation of renal volume represents approximately 2-3 years'
      normal growth in children aged over 2 years.

PMID- 9252432
TI  - The sonographically thickened wall of the upper urinary tract system: correlation
      with other imaging methods.
AB  - BACKGROUND: Sonographically detected, upper urinary tract wall thickening (UUTWT)
      was reported to occur in urinary tract infection, urinary tract stone disease,
      rejection after renal transplantation and vesico-ureteral reflux (VUR). A
      possible association with obstruction can be hypothesized. OBJECTIVE: The
      assessment of a potential relationship of UUTWT with VUR or obstruction in
      patients without one of the above-mentioned conditions. MATERIALS AND METHODS: We
      analyzed 38 patients (74 upper urinary tracts) with at least unilateral UUTWT and
      concomitant imaging studies such as voiding cystourethrography (VCU), intravenous
      urography (IVU) and diuretic renography (DR). RESULTS: At sonography 49 urinary
      tracts showed UUTWT. In 33, ipsilateral VUR could be demonstrated at VCU, 11
      revealed obstruction at IVU and/or DR, and 4 showed non-obstructive pelvicalyceal
      dilatation at IVU and DR. In one patient, all imaging studies were normal. The
      positive predictive value of UUTWT for the presence of VUR was 67.4 % and for
      obstruction it was 22.5 %. Altogether, UUTWT indicated pathology in 98 % of
      urinary tracts. CONCLUSION: After exclusion of urinary tract infection, urinary
      stone disease and prior renal transplantation, the most common associated
      findings in UUTWT are VUR and obstruction. Therefore, VCU seems to be justified
      in all cases of UUTWT. Nonrefluxing systems should be further evaluated with DR
      and/or IVU for exclusion of obstruction.

PMID- 9252433
TI  - Scrotal hematoma due to neonatal adrenal hemorrhage: the value of ultrasonography
      in avoiding unnecessary surgery.
AB  - Scrotal hematoma is an uncommon presentation of neonatal adrenal hemorrhage. Nine
      previous cases of such an association have been reported in the literature, and
      unnecessary surgery was carried out in five of these cases. The authors report
      three new cases observed during a 3-year period and stress the critical role of
      scrotal and abdominal ultrasonography in order to avoid unnecessary surgical
      exploration.

PMID- 9252434
TI  - Disappearing suprarenal masses in fetuses and infants.
AB  - This paper presents 12 infants (9 boys, 3 girls) in whom the diagnosis of a
      suprarenal mass (10 left, 2 bilateral) was made on antenatal sonography. All were
      otherwise healthy neonates who were born at term after a normal pregnancy, labor
      and delivery. The masses ranged from 1 to 3.5 cm in diameter on initial scans at
      gestational ages of 19-35 weeks. Eleven masses were hyperechoic and 4 of these
      contained small, well-defined cysts. The 12th was hypoechoic. Follow-up
      sonography showed complete disappearance of the mass antenatally in 1 case and
      postnatally by 4-6 months in 5 cases; there was marked diminution in the size of
      the mass by 2 months of age in 4 infants, by 4 months in 1 case and by 15 months
      in 1 case. Eleven were managed nonoperatively. Laparotomy (after disappearance of
      the mass) in the 12th case revealed only some fibrous tissue. The 11 echogenic
      masses resemble previously reported imaging findings in infants with
      histologically proven intra-abdominal sequestrated lung. Conservative management
      with careful sonographic follow-up should, therefore, be considered in otherwise
      healthy fetuses or neonates with these imaging findings. We are less certain what
      the hypoechoic mass represented.

PMID- 9252435
TI  - Radiologic-Pathologic Conference of Children's Hospital Boston: intraconal mass
      in the orbit of an infant.
AB  - A 16-month-old boy presented with left exophthalmos. He was found to have an
      enhancing intraconal soft-tissue mass. The differential diagnosis of the mass is
      discussed. The lesion was proven to be a malignant ectomesenchymoma, a very
      unusual tumor.

PMID- 9252436
TI  - Phospholamban ablation enhances relaxation in the murine soleus.
AB  - Phospholamban (PLB) is expressed in slow-twitch skeletal, cardiac, and smooth
      muscles. Several studies have indicated that it is an important regulator of
      basal contractility and the stimulatory responses to isoproterenol in the
      mammalian heart. To determine whether PLB is also a key modulator of slow-twitch
      skeletal muscle contractility, we examined isometric twitch contractions of
      isolated, intact soleus muscles from wild-type (WT) and PLB-deficient mice in
      parallel. Soleus muscles from PLB-deficient mice exhibited a significant (25%)
      decrease in the time to half relaxation, with no change in contraction time
      compared with WT soleus muscles. The observed enhancement of relaxation in the
      PLB-deficient soleus was not associated with alterations in the protein levels of
      either the sarcoplasmic reticular Ca(2+)-adenosinetriphosphatase or the ryanodine
      receptor. Examination of the effects of isoproterenol on the twitch kinetics of
      these muscles revealed 1) no effect on the contraction times of either WT or PLB
      deficient muscles and 2) a significant decrease in the half relaxation time of
      the WT soleus, whereas this parameter remained unchanged in the PLB-deficient
      muscle. Furthermore, with maximal isoproterenol stimulation, the half relaxation
      time of the WT soleus was similar to that of the nonstimulated PLB-deficient
      soleus. These results suggest that PLB is a key determinant of relaxation in slow
      twitch skeletal muscle under basal conditions and during isoproterenol
      stimulation.

PMID- 9252437
TI  - Regulation of mitogenesis by kinins in arterial smooth muscle cells.
AB  - Recent evidence suggests that bradykinin (BK) plays a role in regulating
      neointimal formation after vascular injury. The present study examined the
      mechanism whereby BK regulates platelet-derived growth factor (PDGF) AB-induced
      mitogenesis in smooth muscle cells from rat mesenteric artery. BK, but not other
      activators of phosphoinositidase C (e.g., angiotensin II), inhibited PDGF
      stimulated mitogenesis. The B1 receptor agonist des-Arg9-BK (DABK) was more
      potent than the B2 agonist BK; smaller BK fragments had no activity. In studies
      in which the B2 receptor antagonist HOE-140 {D-Arg0[Hyp3,beta-(2-thienyl)-Ala5,D
      Tic7,Oic 8]BK} and the B1 receptor antagonist DHOE [[D-Arg0,Hyp3,beta-(2-thienyl)
      Ala5,D-Tic7,Oi c8,des-Arg9]BK] were used, both receptors independently mediated
      inhibition of PDGF-induced mitogenesis. There was no evidence for metabolism of
      BK to DABK. The rank potency for activating phosphoinositidase C and increasing
      intracellular Ca2+ (BK > DABK) was opposite that for inhibiting mitogenesis (DABK
      > BK). Inhibition of cyclooxygenase did not prevent the kinin-mediated
      inhibition. Kinetic analysis of the cell cycle effects of kinins on PDGF
      stimulated mitogenesis revealed that continuous exposure to DABK or BK was
      inhibitory even when added shortly before the cells initiated DNA synthesis (S
      phase). However, short-term exposure (5-60 min) to DABK or BK was inhibitory only
      when added after exposure to PDGF. These data suggest that the B1 and B2
      receptors potently inhibited PDGF-stimulated mitogenesis and proliferation by
      activating an alternative signal transduction cascade not involving
      phosphoinositidase C or prostaglandins. The inhibition occurred at a point late
      in progression of the cell cycle from G1 to S and was dependent on the presence
      of kinins after exposure to PDGF.

PMID- 9252438
TI  - Volume transport across tracheal and bronchial airway epithelia in a tubular
      culture system.
AB  - Airway epithelia are thought to play an important role in maintaining the depth
      (volume) and composition of airway surface liquid (ASL). However, due to the
      difficulty in measuring airway epithelial volume flow (Jv) and ASL composition,
      our knowledge of ASL homeostasis is limited. We have developed a permeable
      tubular culture system (biofiber) suitable for growing airway epithelia on the
      biofiber luminal surface, which allows measurements of bioelectric properties and
      Jv. Canine tracheal and bronchial epithelia readily attach, grow to confluence,
      and develop an electrical potential difference (-10 to -40 mV) across the
      biofiber. Using a six-hormone-supplemented medium, we detected a significant
      basal absorptive Jv across both the tracheal cells (0.65 +/- 0.08 microliter.cm
      2.h-1) and bronchial cells (2.21 +/- 0.42 microliters.cm-2.h-1), which was
      significantly reduced by amiloride. Forskolin stimulated a net secretory Jv in
      tracheal biofibers (-0.56 +/- 0.19 microliter.h-1.cm-2) only. When the culture
      medium was supplemented with cholera toxin (CT), the basal absorptive Jv was
      significantly reduced in the bronchial biofibers and the tracheal biofibers
      exhibited net secretion. The forskolin-stimulated secretory Jv in the tracheal
      biofibers was significantly greater in the presence of CT than in its absence (
      1.30 +/- 0.29 microliters.h-1.cm-2), whereas bronchial biofibers exhibited no
      significant Jv response to forskolin. We conclude that the Jv measured in tubular
      culture is highly dependent on the region from which the cells originated as well
      as the composition of the culture medium. Use of the biofiber culture system to
      study airway epithelia should give further insight into factors regulating Jv and
      composition of ASL.

PMID- 9252439
TI  - Effects of fluid flow on intracellular calcium in bovine articular chondrocytes.
AB  - Fluid flow-induced shear stress results in a variety of morphological and
      metabolic changes in cultured bovine articular chondrocytes (BAC). However, the
      mechanism by which the flow signal is transduced into a biological response is
      unknown. Therefore, we investigated the effects of fluid flow on intracellular
      Ca2+ concentration ([Ca2+]i) in BAC. Cells loaded with fura 2 were exposed to
      steady and pulsatile (0.5 Hz) flow at 9, 18, and 34 ml/min in a parallel-plate
      flow chamber. In response to flow, there was a significant and flow rate
      dependent increase in the percentage of cells showing a rise in [Ca2+]i, but no
      effect on the [Ca2+]i response amplitude. There was no significant difference
      between the [Ca2+]i responses to steady and pulsatile flow. Mean intracellular
      Ca2+ response values ranged between 26.2 +/- 1.6 (9 ml/min) and 38.0 +/- 6.8 nM
      (34 ml/min) above basal [Ca2+]i (81.3 +/- 24.1 nM, n = 90). Removal of
      extracellular Ca2+ or addition of Gd3+ significantly reduced the percentage of
      cells responding, suggesting that influx of Ca2+, possibly through
      mechanosensitive channels, contributes to the rise in intracellular Ca2+. Our
      data suggest fluid flow-induced mobilization of intracellular Ca2+ may contribute
      to the mechanism by which mechanical loads are transduced by chondrocytes.

PMID- 9252440
TI  - Measurement of mitochondrial calcium in single living cardiomyocytes by selective
      removal of cytosolic indo 1.
AB  - The aim of the present study was to determine whether, in indo 1 acetoxymethyl
      ester (AM)-loaded rat cardiomyocytes, it was possible to remove cytosolic but not
      mitochondrial indo 1 by promoting loss of cytosolic indo 1 through plasma
      membrane anion pumps (which are blocked by probenecid). Isolated rat ventricular
      myocytes were loaded with indo 1-AM under conditions (15 min at 30 degrees C) in
      which about half of the dye is located within mitochondria. Cells were then
      maintained at 25 degrees C for 2.5 h followed by incubation at 37 degrees C for
      1.5 h. After this "heat treatment," the myocyte fluorescence signal was 44% of
      the value of cells measured before heat treatment, and loss of fluorescence was
      prevented by 1 mM probenecid. The remaining fluorescence was shown to originate
      from mitochondria, since 1) Ca2+ uptake and efflux could be inhibited by
      ruthenium red and clonazepam, respectively, and 2) low concentrations of
      digitonin, which release only cytosolic marker enzymes, decreased fluorescence of
      untreated myocytes but had little effect on the fluorescence signal of heat
      treated cells. We conclude that heat treatment selectively removes cytosolic indo
      1, leaving a signal due to mitochondrial indo 1 only.

PMID- 9252441
TI  - Inhibition of maxi-K currents in ferret portal vein smooth muscle cells by the
      antifungal clotrimazole.
AB  - The antifungal agent clotrimazole (CLT) is a potent small-molecule inhibitor of
      Ca-activated K (KCa) currents of intermediate conductance in murine
      erythroleukemia cells. This study demonstrates that CLT also inhibits large
      conductance KCa currents (maxi-K currents) in acutely dissociated vascular smooth
      muscle (VSM) cells of ferret portal vein. The magnitude of block of a component
      of the whole cell K current by CLT was sensitive to test potential. CLT inhibited
      unitary maxi-K currents in outside-out patches, apparently by decreasing the mean
      open time. A metabolite of CLT lacking an imidazole ring also inhibited K
      currents. In contrast, the antifungal drug ketoconazole increased these same
      currents. Thus the inhibitory action of CLT appears to be due to a direct
      interaction with the channel protein rather than to imidazole block of cytochrome
      P-450 activity. Consistent with inhibition of maxi-K currents by CLT, superfusion
      of strips of portal vein VSM with CLT enhanced isometric tension and spontaneous
      rate of contraction, suggesting that CLT modulation of maxi-K currents may alter
      vasomotor functioning.

PMID- 9252442
TI  - Characterization of volume-sensitive taurine- and Cl(-)-permeable channels.
AB  - Volume-sensitive Cl- channels [ICl(vol)] were studied using taurine efflux and
      patch-clamp experiments in 9HTEo- human tracheal cells. Cells were stimulated
      with the Ca(2+)- elevating agents ATP and ionomycin in isotonic medium or in
      hypotonic solutions. ATP (100 microM) or ionomycin (1 microM) and hypotonic shock
      produced a synergic effect. Indeed, the resulting taurine efflux was much higher
      than the sum of the single effects elicited by ATP, ionomycin, or hypotonic
      medium. The taurine release elicited by hypotonic shock and the potentiation by
      ATP and ionomycin were markedly inhibited by using a Ca(2+)-free extracellular
      medium and by incubating the cells with the membrane-permeable 1,2-bis(2-amino-
      phenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester chelating agent.
      Patch-clamp experiments confirmed the role of Ca2+ on ICl(vol) channels. Swelling
      induced taurine efflux was inhibited by reactive blue 2, suramin, and
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Patch-clamp experiments
      demonstrated that these compounds shift the voltage-dependent inactivation of
      ICl(vol) channels toward more negative values. This study indicates that the
      sensitivity of ICl(vol) to cell volume changes is modulated by intracellular Ca2+
      and that purinergic receptor antagonists represent a new class of CI- channel
      blockers.

PMID- 9252443
TI  - Mechanisms of electrolyte transport across the endometrium. II. Regulation by GRP
      and substance P.
AB  - The purpose of this study was to investigate the regulation of electrolyte
      transport across the porcine endometrium by gastrin-releasing peptide (GRP) and
      substance P (SP). Luminal addition of GRP, neuromedin B (NMB), SP, or neurokinin
      A(NKA) to mucosal tissues mounted in Ussing chambers produced a multiphasic
      change in short-circuit current (Isc) characterized by an initial rapid increase
      and subsequent decrease in current. A similar response was obtained after
      addition of ionomycin or thapsigargin to the tissues. The Isc response to the
      peptides or Ca ionophore was inhibited by pretreatment of the tissues with
      luminal amiloride or benzamil. GRP and SP were more potent [50% effective
      concentration (EC50) of 3 nM] than NMB or NKA (EC50 values of 46 and 26 nM,
      respectively) in producing the decrease in Isc. Pretreatment with the GRP
      receptor antagonist 3-Phe-His-Trp-Ala-Val-D-Ala-His-D-Pro-psi Phe-NH2 blocked the
      Isc response to GRP and NMB but not to SP or NKA, whereas the NMB receptor
      antagonist D-Nal-[Cys-Try-D-Trp-Orn-Val-Cys]-Nal-NH2 was ineffective in
      inhibiting the Isc response to any of the peptides. In contrast, pretreatment of
      the tissue with the nonpeptide SP receptor antagonist CP-99,994 blocked the Isc
      response to SP and NKA but not to GRP or NMB. Experiments with amphotericin B
      permeabilized tissues showed that GRP, SP, ionomycin, and thapsigargin increased
      current through an outwardly rectifying K conductance located on the apical
      membrane of the cells. The K-to-Na selectivity ratio of this conductance was
      calculated to be 2.5:1. These experiments showed that GRP and SP, acting through
      different receptors, produced an increase in K efflux through a Ca-dependent K
      conductance present in the apical membrane of surface endometrial epithelial
      cells. In addition, immunohistochemistry data showed that GRP-like
      immunoreactivity was localized to surface and glandular epithelial cells, whereas
      GRP receptor antibody labeling was observed in both epithelial and stromal cells.
      These results suggest that GRP functions as both an autocrine and paracrine
      regulatory peptide in the endometrium.

PMID- 9252444
TI  - Inhibition of polyamine synthesis influences contractility of intestinal smooth
      muscle in culture.
AB  - Smooth muscle strips from guinea pig ileum were cultured for 5 days and then
      tested for contractile properties to investigate whether endogenous polyamines
      influence excitation-contraction coupling. Inhibition of spermidine and spermine
      synthesis by culture in the presence of the adenosylmethionine decarboxylase
      (EC4.1.1.50) inhibitor CGP-48664 (1-10 microM) decreased spermidine and spermine
      levels by 50% and increased putrescine by 20-fold. After culture with 10 microM,
      but not 1 microM, CGP-48664, the relationship between extracellular Ca2+
      concentration and force in high K(+)-depolarized strips was shifted to the right,
      and phasic contractile activity as well as sensitivity to muscarinic stimulation
      was enhanced. When spermidine and spermine (each 50 microM) were available for
      cellular uptake during culture in the presence of 10 microM CGP-48664, spermidine
      and spermine concentrations were increased, and the effect on Ca2+ sensitivity
      was reversed. In strips cultured with 0 or 1 microM CGP-48664 in the presence of
      50 microM spermidine and 50 microM spermine, no effect on Ca2+ sensitivity was
      observed. Force development relative to intracellular Ca2+ concentration was
      decreased in CGP-48664 (10 microM)-treated strips. The results suggest that
      endogenous polyamines influence excitation-contraction coupling in smooth muscle,
      although overall tissue concentrations may not reflect the polyamine pools
      responsible for this effect.

PMID- 9252445
TI  - Force decline during muscle relaxation promotes calcium release to the cytosol.
AB  - During relaxation of skeletal muscle, an initial rapid decline of intracellular
      Ca2+ concentration ([Ca2+]i) (phase 1), is followed by a brief phase in which the
      decline of [Ca2+]i is markedly slowed or even reversed (phase 2). Phase 2 appears
      as a prominent "bump" on records of the time course of declining [Ca2+]i during
      relaxation. The goal of this study was to test the hypothesis that phase 2
      represents a release of Ca2+ to the cytosol that occurs with net cross-bridge
      detachment during relaxation. The experimental approach was to measure [Ca2+]i
      with indo 1 in stimulated bullfrog semitendinosus muscles and to determine if
      phase 2 was diminished during relaxation of contractions in which cross-bridge
      interactions had been reduced by two different methods: 1) stretching muscles to
      reduce the overlap between actin and myosin filaments or 2) decreasing stimulus
      duration. The results showed that, when either method was used to reduce cross
      bridge interactions during contraction, then the size of phase 2 during
      relaxation was also decreased. Phase 2 was eliminated during relaxation of
      contractions in which cross-bridge interactions had been reduced to a lower
      contraction force approximately 30% of maximum. These findings are consistent
      with the hypothesis that the phase 2 of [Ca2+]i decline represents a release of
      Ca2+ to the cytosol that occurs with net cross-bridge detachment during
      relaxation. This conclusion is consistent with previous studies that suggest that
      cross-bridge detachment lowers the affinity of troponin for Ca2+.

PMID- 9252446
TI  - Mechanism of the acceleration of CO2 production from pyruvate in liver
      mitochondria by HCO3-.
AB  - To investigate the mechanism by which HCO3- accelerates pyruvate metabolism in
      guinea pig liver mitochondria, we measured continuously, at pH 7.4 and 37 degrees
      C, 13C16O2 production from [1-13C]pyruvate by mass spectrometry and NADH
      concentration by fluorescence and analyzed total malate, citrate, and beta
      hydroxybutyrate produced by standard biochemical methods. When [1-13C]pyruvate is
      added to the mitochondrial suspension, 13C16O2 concentration rises steeply in the
      first seconds and then slows to a steady lower rate. Carbonic anhydrase (CA)
      eliminates this initial phase, which shows that decarboxylation of pyruvate
      produces CO2, not HCO3-, and it does this more rapidly than it can equilibrate
      without CA. HCO3- (25 mM) increased 13C16O2 production, O2 consumption and total
      malate and citrate production and decreased NADH concentration and total beta
      hydroxybutyrate production. After obtaining the total amount of 13C16O2, malate,
      citrate, and beta-hydroxybutyrate produced, we calculated that the addition of 25
      mM HCO3- to the suspension medium increased the amount of pyruvate decarboxylated
      by pyruvate dehydrogenase (PDH) 16% and increased the amount carboxylated by
      pyruvate carboxylase 300%. This supports our initial proposal that HCO3-
      accelerates the pyruvate carboxylation, which in turn consumes ATP directly and
      NADH and acetyl CoA secondarily, all of which increase PDH activity. However, we
      found no acceleration of pyruvate decarboxylation by 0.5 and 1 microM free Ca2+
      concentration, unless the mitochondria were uncoupled and ATP was added.

PMID- 9252448
TI  - Ca(2+)-activated K+ channels regulate action potential repolarization in urinary
      bladder smooth muscle.
AB  - The goal of this study was to examine the role of large conductance Ca(2+)
      activated K+ channels in the regulation of cell excitability in urinary bladder
      smooth muscle from the guinea pig. Ca(2+)-activated K+ channels were studied with
      single-channel recording techniques and found to be intracellular Ca2+ and
      voltage dependent and sensitive to external tetraethylammonium and blocked by
      nanomolar concentrations of iberiotoxin (apparent dissociation constant of 4 nM).
      Spontaneous action potentials recorded from intact tissue strips depended on
      external Ca2+ and were inhibited by Ca2+ channel blockers. Iberiotoxin (100 nM)
      significantly altered the configuration of the action potential by increasing the
      duration and peak amplitude of the action potential and decreasing the rate of
      decay. Iberiotoxin also increased the action potential frequency from 0.11 to
      0.29 Hz. This study suggests that Ca(2+)-activated K+ channels play a significant
      role in the repolarization of the action potential and in the maintenance of the
      resting membrane potential of the urinary bladder smooth muscle.

PMID- 9252447
TI  - p70s6k is activated by CCK in rat pancreatic acini.
AB  - The expression and activity of p70s6k-p85s6k in isolated rat pancreatic acini
      were revealed by Western blotting, immunoprecipitation, and kinase assay.
      Cholecystokinin (CCK) stimulation of p70s6k activity was biphasic, with an early
      phase maximum at 5 min and a late phase maximum at 60 min. The threshold
      concentration of CCK to increase p70s6k activity was 3 pM, and the maximal effect
      was seen at 1 nM CCK. Carbachol and bombesin, but not vasoactive intestinal
      peptide, also activated p70s6k. The protein kinase C (PKC) activator (12-O
      tetradecanoylphorbol 13-acetate), the calcium ionophore (ionomycin), and a
      derivative of adenosine 3',5'-cyclic monophosphate induced only a slight increase
      in p70s6k activity. Rapamycin potently blocked both the basal and the CCK
      stimulated p70s6k activity, and this inhibition was reversed by an excess of FK
      506. The phosphatidylinositol 3-kinase inhibitor, wortmannin, potently inhibited
      p70s6k activation by CCK, whereas the tyrosine kinase inhibitor genistein had
      only a partial effect. Neither rapamycin nor wortmannin inhibited amylase release
      at concentrations that inhibited p70s6k activity. Thus the activation pathway of
      p70s6k by CCK is not mediated by PKC or mobilization of intracellular calcium but
      seems to be mediated by phosphatidylinositol 3-kinase. The effect of rapamycin to
      inhibit p70s6k activity is mediated by binding to the immunophyllin FK-506
      binding protein of 12 kDa. The p70s6k is not involved in the secretion of
      digestive enzymes induced by CCK.

PMID- 9252449
TI  - Colocalization of gold-labeled LDL and fibrinogen on platelets: enhanced
      fibrinogen binding induced by LDL.
AB  - Low-density lipoproteins (LDL) specifically bind to the human platelet integrin
      alpha IIb and -beta 3 (Koller et al., J. Biol. Chem. 264: 12412-12418, 1989). We
      show by electron microscopy (EM) that gold (Au)-labeled LDL bind to sites
      randomly distributed on the surface of platelets in suspension. Within a few
      minutes, mobile ligand-receptor complexes are translocated from the surface to
      the open canalicular system (OCS), which finally centralizes as a broad belt.
      Binding and translocation of Au-LDL are independent of stimulation of platelets
      by ADP and are completely reversible. Au-fibrinogen shows a strikingly similar,
      though agonist-dependent, redistribution behavior. Platelets are markedly
      activated by LDL. This activation is initiated by the binding of LDL to the
      plasma membrane receptor, and receptor internalization is probably not required
      for the activation but may instead be one of its consequences. Coincubation with
      Au-LDL and Au-fibrinogen results in more pronounced activation. The amount of OCS
      localized ligands is significantly increased, most likely reflecting enhanced
      receptor recycling. The two ligands show a tendency to segregate in separate
      clusters, indicating differences in their postbinding pathways.

PMID- 9252450
TI  - Overexpression of protein kinase C-zeta isoform increases cyclooxygenase-2 and
      inducible nitric oxide synthase.
AB  - Cyclooxygenase (COX) catalyzes the formation of prostaglandins from arachidonic
      acid. Nitric oxide synthase catalyzes the production of nitric oxide, a short
      lived messenger molecule involved in many diverse cellular processes. Both of
      these enzymes have inducible forms [COX-2 and inducible nitric oxide synthase
      (iNOS), respectively] that respond to environmental stresses, chemicals, and
      extracellular ligands such as interleukin-1, epidermal growth factor, and
      platelet-derived growth factor. The precise cascade of intracellular events that
      leads to the expression of either COX-2 or iNOS is not known. Protein kinase C
      (PKC) is a family of 11 serine-threonine kinases conserved throughout eukaryotic
      species that transduce a wide variety of signals critical for cellular functions.
      Using a retroviral vector to overexpress the zeta-isoform of PKC in rat mesangial
      cells, we demonstrate markedly increased COX-2, prostaglandin E2 (PGE2), iNOS,
      and altered cellular morphology compared with mesangial cells expressing a
      control retroviral vector and untransfected mesangial cells. NIH/3T3 cells
      overexpressing PKC-zeta showed no change in morphology, PGE2 production, COX-2
      expression, or iNOS expression at basal conditions. This suggests a role for PKC
      zeta in the expression of these enzymes in mesangial cells.

PMID- 9252451
TI  - Cyanide suppression of inwardly rectifying K+ channels in guinea pig chromaffin
      cells involves dephosphorylation.
AB  - Treatment of chromaffin cells with cyanide induced a gradual decrease in an
      inwardly rectifying K+ current (IIR), and washout of the mitochondrial inhibitor
      resulted in a rapid recovery of IIR. This diminution of IIR was reversed in a
      time-dependent manner by infusion of ATP or UTP, but not by that of GTP, ITP, or
      CTP. The restoration by ATP was not altered by addition to the pipette solution
      of 50 microM fluorescein 5-isothiocyanate, an inhibitor of various ATPases. A
      similar recovery of IIR occurred with injection of adenosine 5'-O-(3
      thiotriphosphate) (ATP gamma S), but not of 5'-adenylylimidodiphosphate or
      alpha,beta-methyleneadenosine 5'-triphosphate. The ATP gamma S effect was
      biphasic, resulting in first a run-up of the current in ATP-depleted cells
      followed by a rundown of the current. This rundown was almost abolished by
      addition of guanosine 5'-O-(2-thiodiphosphate) to the ATP gamma S solution,
      suggesting the involvement of a G protein. Bath application of the protein kinase
      inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine at 100 microM, but not N
      (2-[methylamino]-ethyl)-5-isoquinolinesulfonamide, induced a reversible
      inhibition of IIR in the presence of pipette ATP, and the inhibition was
      diminished by 1 microM calyculin A, a phosphatase inhibitor. Bath application of
      1 microM phorbol 12,13-dibutyrate did not affect IIR. It is concluded that
      cyanide suppresses inward rectifier K+ channel activity via dephosphorylation and
      that protein kinase C, adenosine 3',5'-cyclic monophosphate-dependent kinase, or
      guanosine 3',5'-cyclic monophosphate-dependent kinase is not involved in
      modulation of the channel.

PMID- 9252452
TI  - cAMP-dependent sulfate secretion by the rabbit distal colon: a comparison with
      electrogenic chloride secretion.
AB  - The ability of a Cl-secreting epithelium to support net secretion of an anion
      other than a halide was investigated with 35SO4 flux measurements across the
      isolated, short-circuited rabbit distal colon. In most experiments, 36Cl fluxes
      were simultaneously measured to validate the secretory capacity of the tissues.
      Serosal addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 0.5
      mM) stimulated a sustained net secretion of SO4 (about -3.0 nmol.cm-2.h-1 from a
      0.20 mM solution) via an increase in the serosal-to-mucosal unidirectional flux,
      whereas Ca ionophore A-23187 (1 microM, serosal) produced a more transient
      stimulation of SO4 and Cl secretion. Net adenosine 3',5'-cyclic monophosphate
      (cAMP)-dependent SO4 and Cl secretion were strongly voltage sensitive,
      principally through the potential dependence of the serosal-to-mucosal fluxes,
      indicating an electrogenic transport process. Symmetrical replacement of either
      Na, K, or Cl inhibited cAMP-dependent SO4 secretion, whereas HCO3-free buffers
      had no effect on SO4 secretion. Serosal bumetanide (50 microM) or furosemide (100
      microM) reduced DBcAMP-stimulated SO4 and Cl secretion, whereas serosal 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid or 4-acetamido-4'
      isothiocyanostilbene-2,2'-disulfonic acid (50 microM) blocked DBcAMP-induced SO4
      secretion while enhancing net Cl secretion and short-circuit current. Mucosal 5
      nitro-2-(3-phenylpropylamino)benzoic acid partially inhibited SO4 secretion and
      completely inhibited Cl secretion. It is concluded that secretagogue-stimulated
      SO4 secretion, like Cl secretion, may be an electrogenic process mediated by
      diffusive efflux through an apical anion conductance. Cellular accumulation of
      SO4 across the basolateral membrane appears to be achieved by a mechanism that is
      distinct from that employed by Cl.

PMID- 9252453
TI  - Effects of pinacidil on K+ channels in human coronary artery vascular smooth
      muscle cells.
AB  - We investigated pinacidil-activated K+ currents in vascular smooth muscle cells
      (VSMC) from human coronary arteries with the patch-clamp method. In 19 of 54
      VSMC, pinacidil (1 and 20 microM) induced a large, nonrectifying, outward current
      [IK(ATP)] and increased voltage-dependent outward K+ currents [IK(Ca)] positive
      to voltages of -25 mV. The pinacidil-induced (1 microM) IK(ATP) was blocked by
      glibenclamide (3 microM) but was not affected by iberiotoxin (100-300 nM).
      Pinacidil activated up to 150 functionally active ATP-dependent K+ channels (KATP
      channels) per cell with a single-channel conductance of approximately 17 pS at
      physiological membrane potentials (between -80 and -30 mV) and K+ gradients (6
      mM/130 mM). In 26 of 54 VSMC, on the other hand, pinacidil (1-20 microM) failed
      to induce IK(ATP) but increased IK(Ca). This current was completely blocked by
      iberiotoxin (100-300 nM) and tetraethylammonium (1 mM) but not by glibenclamide
      (3 microM). The single-channel conductance of the channel underlying IK(Ca) was
      approximately 150 +/- 16 pS between -10 and +30 mV, consistent with large
      conductance, maxi Ca(2+)-activated, K+ channels (BKCa channels). We conclude that
      pinacidil is a nonselective K+ channel opener targeting KATP and BKCa channels.
      Furthermore, the conductance of KATP channels in human coronary arteries is
      likely to be small under physiological conditions.

PMID- 9252454
TI  - Phosphocreatine content in single fibers of human muscle after sustained
      submaximal exercise.
AB  - The effect of sustained submaximal exercise on muscle energetics has been studied
      on the single-fiber level in human skeletal muscle. Seven subjects cycled to
      fatigue (mean 77 min) at a work rate corresponding to approximately 75% of
      maximal O2 uptake. Biopsies were taken from the vastus lateralis muscle at rest,
      at fatigue, and after 5 min of recovery. Muscle glycogen decreased from 444 +/-
      40 (SE) mmol glucosyl units/kg dry wt at rest to 94 +/- 16. Postexercise glycogen
      was inversely correlated (P < 0.01) to muscle content of inosine monophosphate, a
      catabolite of ATP. Phosphocreatine (PCr) in mixed-fiber muscle decreased at
      fatigue to 37% but was restored above the initial value (106.5%, P < 0.025) after
      5 min of recovery. The overshoot was localized to type I fibers. The rapid
      reversal of PCr is in contrast to the slow recovery in contraction force. Pi
      increased at fatigue but less than that expected from the changes in PCr and
      other phosphate compounds. Mean PCr at rest was approximately 20% higher in type
      II than in type I fibers (86.4 +/- 3.6 and 71.6 +/- 1.8 mmol/kg dry wt,
      respectively, P < 0.05), but at fatigue similar PCr contents were observed in the
      two fiber types. Reduction in PCr in all fibers at fatigue suggests that all
      fibers were recruited at the end of exercise. PCr content in single fibers showed
      a great variability in samples at rest, exercise, and recovery. The variability
      was more pronounced than for ATP, and the data suggest that it is due to
      interfiber physiological-biochemical differences. At fatigue ATP was maintained
      relatively high in all single fibers, but a pronounced depletion of PCr was
      observed in a large number of fibers, and this may contribute to fatigue through
      the associated increases in Pi or/and free ADP. It is noteworthy that the
      increase in calculated free ADP at fatigue was similar to that after high
      intensity exercise.

PMID- 9252456
TI  - Molecular characterization of the Na-K-Cl cotransporter of bovine aortic
      endothelial cells.
AB  - The Na-K-Cl cotransporter is an important regulator of endothelial cell volume
      and may also contribute to flux of Na and Cl across the endothelium of the blood
      brain barrier. To date, two Na-K-Cl cotransport isoforms have been identified,
      the cotransporter in secretory epithelia, NKCC1, and that in absorptive renal
      epithelia, NKCC2. Our previous studies showed that a monoclonal antibody to the
      cotransporter of human colonic T84 epithelial cells, an NKCC1 isoform, recognizes
      a 170-kDa glycoprotein from endothelial cells. The molecular identity of the Na-K
      Cl cotransporter present in endothelial cells, however, has been unknown. In
      addition, although evidence has been provided that phosphorylation of the
      endothelial cotransporter plays a role in regulating its activity, little is
      known about potential sites for protein kinase interaction with the
      cotransporter. The present study was conducted to determine the molecular
      structure of the endothelial Na-K-Cl cotransporter. Using a 1.0-kilobase (kb)
      cDNA fragment from a conserved region of the T84 cell cotransporter, we screened
      a bovine aortic endothelial cell cDNA library and subsequently identified and
      sequenced two overlapping clones that together spanned the entire coding region.
      The endothelial cotransporter is a 1,201-amino acid protein with 12 putative
      transmembrane segments and large amino and carboxy termini, each containing
      several consensus sites for phosphorylation by protein kinases. Comparison of the
      endothelial cotransporter amino acid sequence with known NKCC1 and NKCC2
      sequences revealed a 96% identity with NKCC1. Northern blot analysis using a cDNA
      probe from the endothelial cotransporter revealed high expression of
      approximately 7.5-kb transcripts in a number of bovine tissues. Finally, a
      prominent expression of Na-K-Cl cotransporter was found by Western blot analysis
      in both cultured and freshly isolated endothelial cells of bovine aorta and
      cerebral microvessels.

PMID- 9252455
TI  - Extracellular matrix-anchored serum amyloid A preferentially induces mast cell
      adhesion.
AB  - Mast cells are known to accumulate in various inflammatory processes, some of
      which are known to be associated with increased local and systemic levels of
      acute-phase reactants such as serum amyloid A (SAA) or with amyloid deposition.
      The mechanism(s) by which mast cells are recruited to these sites, however, has
      not been fully elucidated. It has recently been shown that SAA interacts with
      extracellular matrix (ECM) components and thereby acts as a chemoattractant and
      regulator of immune cell migration. On the basis of these observations, we
      examined the effect of SAA on mast cell adhesion to ECM, an essential step in
      cellular transmigration. We could first demonstrate strong specific binding of
      recombinant human SAA (rSAA) to murine mast cells using flow cytometry. Moreover,
      radiolabeled rSAA was found to bind, in a saturable manner, to mast cells,
      reaching a binding affinity of 10(-8) M. When immobilized by preincubation with
      ECM, SAA or its proteolytically degraded amyloid A fragment (amino acid residues
      2-82), which contains RGD-related adhesion motif but not the COOH-terminal
      portion of SAA (amino acid residues 77-104), induced the adhesion of resting mast
      cells to ECM or laminin. SAA and AA, in soluble or immobilized forms, did not
      activate mast cells to release mediators. Mast cell adhesion to the immobilized
      ECM-SAA complex appeared to occur through an integrin recognition, inasmuch as
      adhesion was calcium dependent and could be blocked by an RGD-containing peptide
      or by anti-CD29 monoclonal antibody. Genistein also inhibited adhesion,
      indicating that tyrosine kinase activity was involved. These data suggest that
      SAA bound to ECM may serve as an important inducer of mast cell adhesion, thus
      regulating mast cell recruitment and accumulation at these sites, which in turn
      could potentiate further pathology.

PMID- 9252457
TI  - Length-dependent potentiation and myosin light chain phosphorylation in rat
      gastrocnemius muscle.
AB  - Changes in muscle length affect the degree of staircase potentiation in skeletal
      muscle, but the mechanism by which this occurs is unknown. In this study, we
      tested the hypothesis that length-dependent change in staircase is modulated by
      phosphorylation of the myosin regulatory light chains (RLC), since this is
      believed to be the main mechanism of potentiation. In situ isometric contractile
      responses of rat gastrocnemius muscle during 10 s of repetitive stimulation at 10
      Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. The degree of
      enhancement of developed tension during 10 s of repetitive stimulation was
      observed to be length dependent, with increases of 118.5 +/- 7.8, 63.1 +/- 3.9,
      and 45.6 +/- 4.1% (means +/- SE) at Lo - 10%, Lo, and Lo + 10%, respectively.
      Staircase was accompanied by increases in the average rate of force development
      of 105.6 +/- 7.7, 55.6 +/- 4.1, and 37.2 +/- 4.4% for Lo - 10%, Lo, and Lo + 10%,
      respectively. RLC phosphorylation after 10 s of 10-Hz stimulation was higher than
      under resting conditions but not different among Lo - 10% (40 +/- 3.5%), Lo (35
      +/- 3.5%), and Lo + 10% (41 +/- 3.5%). This study shows that there is a length
      dependence of staircase potentiation in mammalian skeletal muscle that may not be
      directly modulated by RLC phosphorylation. Interaction of RLC phosphorylation
      with length-dependent changes in Ca2+ release and intermyofilament spacing may
      explain these observations.

PMID- 9252458
TI  - Energy turnover of vascular endothelial cells.
AB  - Two noninvasive methods, calorimetry and 31P nuclear magnetic resonance (NMR),
      were used to further define energy-consuming and energy-providing reactions in
      endothelial cells. With 31P-NMR, cellular ATP content was measured; with
      calorimetry, heat flux as a result of ATP turnover was measured. For these
      measurements, pig aortic endothelial cells were cultured on microcarrier beads
      and perfused in a column at constant flow rate. Pig aortic endothelial cells
      synthesize ATP mainly through glycolysis and, as determined by NMR, contain no
      phosphocreatine. In such a system, calorimetry-measured heat flux reflects rate
      of cellular ATP turnover. By use of inhibitors of ATP-dependent processes, the
      following changes in basal heat flux (231 +/- 65.5 microW/mg protein) were
      obtained: 18% for 2,3-butanedione monoxime (inhibitor of actomyosin-ATPase), 17%
      for wortmannin (inhibitor of myosin light chain kinase), 10% for cytochalasin D
      (inhibitor of actin polymerization), 23% for cycloheximide (inhibitor of protein
      synthesis), 11% for thapsigargin (inhibitor of endoplasmic reticulum Ca(2+)
      ATPase), and 6% for bafilomycin A1 (inhibitor of lysosomal H(+)-ATPase).
      Cytochalasin D, 2,3-butanedione monoxime, wortmannin, and thapsigargin caused
      changes in F-actin distribution, as revealed by rhodamine-phalloidin
      cytochemistry. In a separate experimental series, when cells were perfused with a
      medium containing no glucose, heat flux decreased by 40% while cellular ATP
      remained unchanged. Inhibition of glycolysis with 2-deoxy-D-glucose decreased
      heat flux by 73%, and ATP was no longer visible with 31P-NMR. Despite this
      massive ATP depletion, which was maintained for 3 h, cells fully recovered heat
      flux and ATP when 2-deoxy-D-glucose was removed. The results, together with
      previously published data for Na(+)-K(+)-ATPase [M. L. H. Gruwel, C. Alves, and
      J. Schrader. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H351-H358, 1995],
      demonstrate that > 70% of total ATP-consuming processes of endothelial cells can
      be attributed to specific cellular processes. Actomyosin-ATPase (18%) and protein
      synthesis (23%) comprise the largest fraction. At least three-fourths of ATP
      synthesized is provided by glycolysis. Endothelial cells exhibit the remarkable
      ability to coordinate downregulation of ATP synthesis and consumption when
      glycolysis is inhibited.

PMID- 9252459
TI  - Swelling-activated efflux of taurine and other organic osmolytes in endothelial
      cells.
AB  - We used a combined biochemical, pharmacological, and electrophysiological
      approach to study the effects of hyposmotic swelling on organic osmolyte efflux
      in endothelial cells (EC). In [3H]taurine-loaded monolayers of calf pulmonary
      artery EC (CPAEC), hyposmolality activated time- and dose-dependent effluxes of
      [3H]taurine. Swelling-activated [3H]taurine efflux (Jtau swell)in CPAEC was
      inhibited by the anion channel blockers tamoxifen, 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB), 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid (DIDS), fenamates, and also quinine (in a pH-dependent manner),
      ATP, and the phospholipase A2 inhibitor 4-bromophenacyl bromide. In contrast,
      Jtau swell was partly or totally insensitive to bumetanide, forskolin, phorbol 12
      myristate 13-acetate, and staurosporine. Swelling also activated myo-[3H]inositol
      efflux that was blocked by tamoxifen, NPPB, DIDS, and niflumic acid. Moreover,
      the cellular content of taurine and other amino acids was significantly reduced
      in osmotically activated CPAEC. Finally, in whole cell patch-clamp experiments,
      taurine, glycine, aspartate, and glutamate exhibited significant permeability for
      swelling-activated anion channels. In conclusion, hyposmotic swelling activates
      efflux of taurine and other organic osmolytes in EC. In addition, our results
      suggest that anion channels may provide a pathway for swelling-activated efflux
      of organic osmolytes in EC.

PMID- 9252460
TI  - bFGF induces BCK promoter-driven expression in muscle via increased binding of a
      nuclear protein.
AB  - Changes in gene expression occurring during skeletal muscle differentiation are
      exemplified by downregulation of brain creatine kinase (BCK) and induction of
      muscle creatine kinase (MCK). Although both are transcriptionally regulated,
      there appears to be no transcription factor-element overlap, suggesting that
      their coordinate expression results from culture medium-related influences. Basic
      fibroblast growth factor (bFGF) prevents myogenesis and represses MCK expression
      by inhibiting transcriptional activation. It was hypothesized that bFGF similarly
      influenced BCK by inducing its expression. Accordingly, BCK promoter constructs
      were transiently transfected into C2C12 cells and, after a switch to
      differentiation medium, were treated with bFGF, bFGF plus herbimycin, adenosine
      3',5'-cyclic monophosphate (cAMP), or phorbol 12-myristate 13-acetate (PMA).
      Analyses demonstrated that bFGF responsiveness was contained within a 33-base
      pair element. Electromobility shift assays showed that bFGF induction increased
      the abundance of the nuclear factor binding the element. Both effects were
      prevented by herbimycin. Neither cAMP nor PMA specifically induced the construct
      containing the bFGF-responsive element. The induced factor required
      phosphorylation to bind, implying that bFGF-mediated increases in binding may be
      due to transcription factor phosphorylation.

PMID- 9252461
TI  - Possible thiol group involvement in intracellular pH effect on low-conductance
      Ca(2+)-dependent K+ channels.
AB  - We have studied the effect of intracellular pH (pHi) shifts on the activity of
      Ca(2+)-dependent, inwardly rectifying K+ channels of HeLa cells. Recordings of
      macroscopic currents in symmetrical 145 mK K+ and internal pH of 7.4 gave
      moderate inward rectification of the current. At pH 6.4, inward rectification was
      more marked, whereas it switched to outward rectification at pH 8.2. In excised
      inside-out membrane patches, similar changes in pHi did not affect the single
      channel conductance of the channels underlying the Ca(2+)-dependent K+ currents.
      At neutral pH, the open state probability (Po) was independent of voltage in the
      range from -70 to 70 mV. At alkaline pH, Po became voltage dependent, decreasing
      at negative potentials and increasing with depolarization compared with pH 7.4.
      These changes accounted for the pH-dependent changes in rectification of the
      macroscopic current. The possibility that voltage dependence might arise from the
      ionization of a thiol group was tested by using thiol-directed reagents. The
      decrease in Po produced by intracellular alkalinization at negative potential was
      reverted by treatment with N-ethylmaleimide, 5,5'-dithiobis(2-nitrobenzoic acid),
      and 2,2'-dithiodipyridine. The effect of intracellular alkalinization is
      speculated to occur through ionization of a cysteine group(s) within the field of
      the membrane affecting gating.

PMID- 9252462
TI  - Thrombin promotes endothelial cell alignment in Matrigel in vitro and
      angiogenesis in vivo.
AB  - We have tested the effect of thrombin on endothelial cell tube formation in vitro
      and angiogenesis in vivo. Thrombin induces the differentiation of endothelial
      cells into capillary structures in a dose-dependent fashion (0.1-0.3 units
      thrombin/ml) on Matrigel, a laminin-rich reconstituted basement membrane matrix.
      At higher thrombin concentrations (1.0 unit/ml), a suppression of tube formation
      is evident, probably due to downregulation (desensitization) of the thrombin
      receptor. D-Phe-Pro-Arg-CH2Cl-thrombin is without effect when used alone, but it
      abolishes the tube-promoting effect of thrombin when used in combination with
      thrombin, indicating the involvement of the catalytic site of thrombin.
      Activation of protein kinase C (PKC) seems to be the transduction mechanism
      involved in the stimulation of tube formation by thrombin. Ro-318220 (3
      micrograms/ml), a specific inhibitor of PKC, completely abolishes the stimulatory
      effect of thrombin. In the in vivo Matrigel system of angiogenesis, there is a 10
      fold increase in endothelial cell infiltration in response to thrombin. These
      results provide evidence for the angiogenesis-promoting effect of thrombin in
      vivo and the induction by thrombin of the angiogenic phenotype of endothelial
      cells in vitro in the absence of other cell types such as smooth muscle cells,
      pericytes, and inflammatory cells.

PMID- 9252463
TI  - Morphological and biochemical evidence of muscle hyperplasia following weight
      lifting exercise in rats.
AB  - We used a rat model of weight lifting to examine the serial biochemical and
      morphological changes following muscle fiber hyperplasia during 14 days of
      exercise. [3H]thymidine and [14C]leucine labeling were used to determine the
      serial changes in cellular mitotic activity and the level of amino acid uptake
      and myosin synthesis. Morphological changes were assessed with light and
      transmission electron microscopy, whereas proliferation of cells was evaluated
      immunohistochemically with 5-bromo-2'-deoxyuridine (BrdU). The intensity of the
      exercise and degree of muscle damage were monitored by serum creatine kinase (CK)
      activity. Damaged fibers were sparsely distributed, and a significant CK leakage
      was observed 30-60 min after exercise. Anti-BrdU-positive cells were observed in
      damaged fibers and at the periphery of undamaged fibers. Changes typical of
      muscle regeneration were observed; however, the formation of new fibers in the
      interstitial space was also evident. The mitotic activity also changed and
      reflected the appearance of anti-BrdU-positive cells and activated satellite
      cells. Amino acid uptake increased during the first week of exercise, probably
      reflecting muscle hypertrophy and synthesis of other noncontractile related
      proteins. The uptake also increased during the second week, probably due to
      hyperplasia, a finding also supported by electron microscopy. Our results suggest
      that one bout of weight-lifting exercise in untrained rats induced muscle
      hyperplasia following regeneration. The process of muscle hyperplasia was
      activated by muscle fiber damage in our model.

PMID- 9252465
TI  - Basis of passive tension and stiffness in isolated rabbit myofibrils.
AB  - By examining the mechanical properties of isolated skeletal and cardiac
      myofibrils in calcium-free, ATP-containing solution, we attempted to separate the
      stiffness contribution of titin filaments from that of weakly bound cross
      bridges. Efforts to enhance weak cross-bridge binding by lowering ionic strength
      were met by clear contractile responses. Even at low temperature, myofibrils
      bathed in low-ionic-strength relaxing solution generated increased force and
      exhibited sarcomere shortening, apparently caused by active contraction. At
      normal ionic strength, myofibril stiffness, estimated from the force response to
      rapid sinusoidal oscillations, increased steadily with sarcomere extension up to
      a strain limit. No obvious stiffness contribution from weak cross bridges was
      detectable. Instead, the stiffness response, which was frequency dependent at all
      sarcomere lengths, was apparently generated by the viscoelastic titin filaments.
      During imposed stretch-hold ramps, both peak force/stiffness and the amount of
      subsequent stress relaxation increased with higher stretch rates, larger stretch
      amplitudes, and longer sarcomere lengths. We conclude that, for a truly relaxed
      myofibril, both passive force and dynamic stiffness principally reflect the
      intrinsic viscoelastic properties of the titin filaments.

PMID- 9252464
TI  - Na+/Ca2+ exchanger in Drosophila: cloning, expression, and transport differences.
AB  - cDNAs for the Na+/Ca2+ exchanger from Drosophila melanogaster (Dmel/Nck) have
      been cloned by homology screening using the human heart Na+/Ca2+ exchanger cDNA.
      The overall deduced protein structure for Dmel/Nck is similar to that of
      mammalian Na+/Ca2+ exchanger genes NCX1 and NCX2, having six hydrophobic regions
      in the amino terminus separated from six at the carboxy-terminal end by a large
      intracellular loop. Sequence comparison of the Drosophila exchanger cDNAs with
      NCX1 and NCX2 Na+/Ca2+ exchangers are approximately 46% identical at the deduced
      amino acid level. Consensus phosphorylation sites for both protein kinase C and
      protein kinase A are present on the intracellular loop region of the Dmel/Nck.
      Alternative splicing for the Dmel/Nck gene is suggested in the same intracellular
      loop region as demonstrated for NCX1. Functionally, the Drosophila Na+/ Ca2+
      exchanger expressed in oocytes differs from expressed mammalian NCX1 with regard
      to Ca2+ transport in Ca2+/ Ca2+ exchange and the effect of monovalent-dependent
      Ca2+/ Ca2+ exchange. The Dmel/Nck gene maps to chromosome 3 (93A-B) using in situ
      hybridization to polytene chromosomes, the same position as the Na(+)-K(+)
      ATPase, a related transporter. We conclude that, although extracellular Na+
      concentration-dependent Ca2+ transport is subserved by both human and Drosophila
      Na+/Ca2+ exchangers, there are clear and important differences in the
      transporters, which should be useful in deducing how the Na+/Ca2+ exchanger
      protein function depends on its structure.

PMID- 9252466
TI  - Upregulation of COX-2 in cerebral microvascular endothelial cells by smooth
      muscle cell signals.
AB  - Cyclooxygenase (COX) isoform expression, intracellular localization, and function
      in endothelial cells from the newborn pig cerebral microvessels were investigated
      using COX-1- and COX-2-specific antibodies and the COX-2 inhibitor NS-398.
      Cerebral microvessels, microvascular endothelium, and cultured endothelial cells
      constitutively express both COX-1 and COX-2. NS-398 inhibits 70-90% of
      endothelial prostanoid production. Endothelial cells grown in noncontact
      coculture with smooth muscle cells for 24-48 h demonstrate a stable induction of
      COX-2 protein and an NS-398-sensitive increase in prostanoid synthesis. The
      induction of endothelial COX in mixed cell coculture is accompanied by
      intracellular redistribution of COX-2. In cocultured endothelial cells, COX-2 is
      observed in the nucleus, nuclear envelope, and cytoplasm, compared with the
      mainly intranuclear localization of COX-2 in cells cultured separately. No
      changes were observed in COX-1 protein, localized in endothelial cell cytoplasm
      and the nuclear envelope. These results indicate that smooth muscle cells may
      modify endothelial function by upregulating COX-2, which is a major functional
      COX isoform in cerebral microvascular endothelial cells.

PMID- 9252467
TI  - Sapecin B, a novel fly toxin, blocks macroscopic K+ currents in the GH3 rat
      pituitary cell line.
AB  - Sapecin B is structurally homologous to charybdotoxin (CTX), which is found in
      scorpion venom. This study investigated the effects of sapecin B on the Ca(2+)
      activated K+ currents [IK(Ca)] and the rapidly inactivating K+ currents in clonal
      rat GH3 pituitary cells with whole cell voltage-clamp methods. Sapecin B (20 nM)
      reversibly blocked the CTX-sensitive Ix(Ca) (the BK current) in a dose-dependent
      manner, with a half-maximal inhibitory concentration of approximately 0.9 nM,
      comparable to that of 0.08-0.4 nM for CTX. The Ca2+ currents in GH3 cells,
      however, were not affected by sapecin B (40 nM), indicating that the blockade of
      IK(Ca) by sapecin B is not a secondary effect of Ca2+ current inhibition. The
      effect of sapecin B on IK(Ca) resembled that of CTX, as expected from the
      structural similarities shared by CTX and sapecin B. We also found that sapecin B
      largely inhibited the 4-aminopyridine-sensitive, rapidly inactivating K+ currents
      in a dose-dependent manner, with a half-maximal inhibitory concentration of
      approximately 40 nM, whereas CTX had little effect on this current in GH3 cells.
      Sapecin B may thus provide a useful tool, complementary to CTX, for probing the
      functional role of molecular domains in the BK channels and the structural
      similarities common to the BK and the rapidly inactivating A-type K+ channels.

PMID- 9252468
TI  - Early functional and biochemical adaptations to low-frequency stimulation of
      rabbit fast-twitch muscle.
AB  - To examine mechanisms underlying force reduction after the onset of chronic low
      frequency (10 Hz) stimulation (CLFS), we exposed rabbit tibialis anterior muscles
      to various durations of CLFS. To follow changes in isometric contractile
      properties and electromyographic (EMG) activity, we studied stimulated and
      contralateral muscles during a terminal test at 10 Hz for 10 min. In addition,
      activities and protein amounts of the sarcoplasmic reticulum Ca(2+)-ATPase,
      content of Na(+)-K(+)-ATPase, and expression patterns of triad junction
      components were examined. Force output and EMG amplitude declined abruptly soon
      after the onset of stimulation, suggesting refractoriness of a large fiber
      population. Although twitch force and to a lesser extent EMG activity gradually
      recovered after stimulation for 6 days and longer, the muscles exhibited
      profoundly altered properties, i.e., enhanced fatigue resistance, absence of
      twitch potentiation, and prolonged contraction and relaxation times. These
      changes were associated with significant increases in Na(+)-K(+)-ATPase
      concentration and significant decreases in Ca(2+)-ATPase, ryanodine receptor,
      dihydropyridine receptor, and triadin concentrations over the course of the 20
      days of stimulation. Alterations in excitability, Ca2+ handling, and excitation
      contraction coupling prior to changes in myofibrillar protein isoforms may thus
      be responsible for early functional alterations.

PMID- 9252470
TI  - A volume-sensitive, IP3-insensitive Ca2+ store in vascular endothelial cells.
AB  - The mechanism by which cell swelling and other physical forces increase the
      intracellular Ca2+ concentration ([Ca2+]i) is poorly defined. In vascular
      endothelial cells, the increase in [Ca2+]i after hypotonic swelling was
      independent of external Ca2+ and membrane potential, was not blocked by La3+ or
      Gd3+, and was prevented by thapsigargin, indicative of intracellular release.
      This release also occurred after depletion of agonist-sensitive Ca2+ stores. In
      cells in which the plasma membrane was permeabilized with saponin, hypotonic
      medium stimulated release of 45Ca2+ from a thapsigargin-sensitive site. Isosmotic
      substitutions with sucrose or urea revealed that this release was due
      specifically to swelling and not to changes in osmolarity or ion concentrations.
      This volume-sensitive release was inhibited by high concentrations of La3+ and
      Gd3+ in a time-dependent manner, suggesting inhibition from within the storage
      compartment. Release was not inhibited by ruthenium red or by prior stimulation
      with inositol 1,4,5-trisphosphate (IP3), indicating that the volume-sensitive
      storage site is distinct from mitochondria and from stores sensitive to ryanodine
      or IP3. The results suggest the presence of a novel, stretch-activated Ca2+ store
      in endothelial cells that could contribute to their mechanosensitivity.

PMID- 9252469
TI  - Activation of glycolysis in human muscle in vivo.
AB  - We tested the cytoplasmic control mechanisms for glycolytic ATP synthesis in
      human wrist flexor muscles. The forearm was made ischemic and activated by
      maximal twitch stimulation of the median and ulnar nerves in 10 subjects. Kinetic
      changes in phosphocreatine, Pi, ADP, ATP, sugar phosphates, and pH were measured
      by 31P magnetic resonance spectroscopy at 7.1-s intervals. Proton production was
      determined from pH and tissue buffer capacity during stimulation. Glycolysis was
      activated between 30 and 50 stimulations, and the rate did not significantly
      change through the stimulation period. The independence of glycolytic rate on
      [Pi], [ADP], or [AMP] indicates that feedback regulation by these metabolites
      could not account for this activation of glycolysis. However, glycolytic H+ and
      ATP production increased sixfold from 0.5 to 3 Hz, indicating that glycolytic
      rate reflected muscle activation frequency. This dependence of glycolytic rate on
      muscle stimulation frequency and independence on metabolite levels is consistent
      with control of glycolysis by Ca2+.

PMID- 9252472
TI  - Bursting behavior during fixed-delay stimulation of spontaneously beating chick
      heart cell aggregates.
AB  - Spontaneously beating embryonic chick atrial heart cell aggregates were
      stimulated with depolarizing current pulses delivered at a fixed delay after each
      action potential. This preparation is an experimental model of a reentrant
      tachycardia. During fixed-delay stimulation, bursting behavior was typically
      observed for a wide range of delays. Episodes of bursting at a rate faster
      (slower) than control were followed by overdrive suppression (underdrive
      acceleration). We use a simple nonlinear model, based on the interaction between
      excitability and overdrive suppression, to describe these dynamics. A modified
      version of the Shrier-Clay ionic model of electrical activity of the embryonic
      chick heart cell aggregates that includes a simplified Na+ pump term is also
      presented. We show that the complex patterns during fixed-delay stimulation arise
      as a result of delicate interactions between overdrive suppression and phase
      resetting, which can be described in terms of the underlying ionic mechanisms.
      This study may provide a basis for understanding incessant tachycardias in the
      intact heart, as well as an alternative mechanism for the emergence of bursting
      activity in other biologic tissue.

PMID- 9252471
TI  - Expression of adenylyl cyclase mRNAs in the adult, in developing, and in the
      Brattleboro rat kidney.
AB  - The activity and expression of adenylyl cyclases (AC) were examined in the adult
      rat renal cortex and medulla. Northern blot analysis and in situ hybridization
      demonstrated that AC-6 was the predominant isoform in the adult rat kidney,
      whereas AC-4, -5, and -9 had a lower expression. AC-4 expression was higher in
      the cortex, and AC-5 and AC-6 were higher in the medulla. AC-9 expression was at
      the same level in both regions. AC activity was high in the fetus and declined in
      the adult. At all stages, AC activity was sensitive to parathyroid hormone,
      whereas no stimulation by vasopressin and isoproterenol was found in the fetus
      and the neonate. AC-5 and AC-6 mRNAs increased at day 1 and then markedly
      decreased, paralleling the decline in AC activity. The mRNA of AC-4 did not
      change and that of AC-9 increased markedly until adult. In the homozygous
      Brattleboro rat kidney, the expression of all these isoforms was decreased.

PMID- 9252473
TI  - Specific adaptations in muscle and adipose tissue in response to chronic systemic
      glucose oversupply in rats.
AB  - Rats minimize hyperglycemia during chronic glucose infusion, but the metabolic
      processes are unclear. We investigated the tissues involved and the role of
      altered insulin sensitivity. Cannulated rats were infused with glucose (40 mg.kg
      1.min-1) for 1 or 4 days or with saline (control). Hyperglycemia at 1 day (15.3
      +/- 1.0 mM) was absent at 4 days (7.5 +/- 0.3 mM), but hyperinsulinemia
      persisted. Whole body glucose disposal was similarly elevated at 1 and 4 days,
      implying increased glucose clearance at 4 days (2-fold, P < 0.001). Muscle
      glucose uptake and glycogen content declined in glucose-infused rats from 1 to 4
      days, whereas white adipose tissue (WAT) glucose uptake (6-fold, P < 0.001) and
      lipogenesis (3-fold, P < 0.001) increased. Muscle and liver triglyceride were
      doubled at both 1 and 4 days (P < 0.05 vs. control). Insulin sensitivity
      (assessed during euglycemic clamps) decreased in muscle to 34% of control at 1
      and 4 days (P < 0.001 vs. control) and increased fivefold in WAT from 1 to 4 days
      (P < 0.05). Thus chronic glucose infusion results in a slow increase in
      efficiency of glucose clearance with enhanced WAT glucose uptake, lipogenesis,
      and insulin action. In contrast, the adaptation reduces glucose oversupply to
      muscle. Muscle shows sustained insulin resistance, with lipid accumulation a
      possible contributing factor.

PMID- 9252474
TI  - Effect of methionine-free total parenteral nutrition and insulin-like growth
      factor I on tumor growth in rats.
AB  - The objectives of this study were to evaluate the effect of insulin-like growth
      factor I (IGF-I) on the fractional synthesis rate (FSR) of muscle and whole body
      protein breakdown rate (WPBR) during methionine-free total parenteral nutrition
      (MTPN). We also determined whether the inhibition of endogenous methionine
      availability reduced tumor protein synthesis. AH109A hepatoma cells were
      inoculated onto the backs of Donryu rats on day 0. On day 10, the rats were
      catheterized for TPN and assigned to one of four groups: 1) standard TPN (STPN),
      2) STPN + IGF-I, 3) MTPN, or 4) MTPN + IGF-I. The addition of IGF-I to MTPN
      reduced the loss of body weight by both increasing muscle FSR and reducing WPBR.
      The tumor FSR did not differ between MTPN + IGF-I and MTPN. The methionine
      extraction ratio from the liver was negative with MTPN + IGF-I but positive in
      the other groups. We concluded that IGF-I blockage of endogenous methionine
      release from peripheral protein sites was associated with a shift to liver
      derived methionine, with no change in tumor growth in MTPN-treated rats.

PMID- 9252475
TI  - Accelerated glycogenolysis in uremia and under sucrose feeding: role of
      phosphorylase alpha regulators.
AB  - To understand the mechanism of hepatic glycogen depletion found in uremia and
      under sucrose feeding, we examined net hepatic glycogenolysis-associated active
      enzymes and metabolites during fasting. Liver was taken 2, 7, and 18 h after food
      removal in uremic and pair-fed control rats fed either a sucrose or cornstarch
      diet for 21 days. Other uremic and control rats fasted for 18 h were refed a
      sucrose meal to measure glycogen increment. Glycogen storage in uremia was
      normal, suggesting effective glycogen synthesis. During a short fast, sucrose
      feeding and uremia enhanced net glycogenolysis through different but additive
      mechanisms. Under sucrose feeding, there were high phosphorylase alpha levels
      associated with hepatic insulin resistance. In uremia, phosphorylase alpha levels
      were low, but the enzyme was probably activated in vivo by a fall of inhibitors
      (ATP, alpha-glycerophosphate, fructose-1,6-diphosphate, and glucose) and a rise
      of Pi, as verified in vitro. Enhanced gluconeogenesis was also suggested, but
      excessive hepatic glucose production was unlikely in uremia. During fasting,
      hypoglycemia occurred in uremia due to reduced glycogenolysis, inefficient
      hepatic gluconeogenesis, and impaired renal gluconeogenesis. This may be relevant
      to poor fasting tolerance in uremia, which could be aggravated under excessive
      sucrose intake.

PMID- 9252476
TI  - Phorbol esters stimulate muscle glucose transport by a mechanism distinct from
      the insulin and hypoxia pathways.
AB  - Glucose transport in skeletal muscle can be stimulated by insulin and also by
      contractions and hypoxia. Activation of protein kinase C (PKC) stimulates glucose
      transport in muscle and other insulin-responsive cells. This study was performed
      to determine if the diacylglycerol (DAG)/phorbol ester-sensitive PKC isoforms
      participate in insulin and/or hypoxia-stimulated glucose transport in skeletal
      muscle. The phorbol ester 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA)
      induced a three- to fourfold increase in glucose transport in rat epitrochlearis
      muscle. The effects of dPPA on glucose transport and on cell surface GLUT-4 were
      completely additive to the maximal effects of insulin or hypoxia. Phorbol ester
      treatment induced 5- to 10-fold increases in phosphorylation of the myristoylated
      alanine-rich C kinase substrate protein in muscle, whereas insulin and hypoxia
      had negligible effects. Calphostin C, an inhibitor of DAG-sensitive PKC isoforms,
      decreased glucose transport stimulation by dPPA but not by insulin or hypoxia.
      These results provide evidence that activation of DAG/phorbol ester-sensitive
      PKCs is not involved in the pathways by which either insulin or hypoxia
      stimulates muscle glucose transport. They also show that activation of this group
      of PKCs increases glucose transport by a mechanism that is independent of and
      additive to the effects of insulin or hypoxia.

PMID- 9252477
TI  - Cholate inhibits high-fat diet-induced hyperglycemia and obesity with acyl-CoA
      synthetase mRNA decrease.
AB  - The effects of sodium cholate on high-fat diet-induced hyperglycemia and obesity
      were investigated. Insulin resistance was estimated by measuring 2-deoxyglucose
      uptake in epitrochlearis muscles incubated in vitro. Addition of 0.5% cholate to
      high-safflower oil diet completely prevented high fat-induced hyperglycemia and
      obesity in C57BL/6J mice with a slight decrease of energy intake but with no
      inhibition of fat absorption. Furthermore, the addition of cholate decreased
      blood insulin levels and prevented high-fat diet-induced decrease of glucose
      uptake in epitrochlearis. However, there was no change in the unsaturation index
      of fatty acids in skeletal muscles and in GLUT-4 levels by cholate. In liver,
      cholate addition resulted in cholesterol accumulation and completely prevented
      high-fat diet-induced triglyceride accumulation. The changes of triglyceride
      level in the liver were paralleled to the changes of acyl-CoA synthetase (ACS)
      mRNA. ACS catalyzes the formation of acyl-CoA from fatty acid, and acyl-CoA is
      utilized for triglyceride formation in liver. ACS has a sterol-responsive element
      1 in its promoter region. These data indicate that the favorable effects of
      cholate could be partly the result of downregulation of ACS mRNA.

PMID- 9252478
TI  - Poor fetal nutrition causes long-term changes in expression of insulin signaling
      components in adipocytes.
AB  - Insulin action on adipocytes was studied in the offspring of mothers who had been
      fed either a control (20% protein) or a low (8%)-protein diet during pregnancy
      and lactation. Adipocytes isolated from low-protein offspring had significantly
      higher basal and insulin-stimulated glucose uptakes than controls. This may be
      related to a threefold increase in insulin receptors in low-protein adipocytes.
      Consistent with these observed changes in glucose transport, adipocytes from low
      protein animals had significantly higher basal and insulin-stimulated insulin
      receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3-kinase)
      activities. There was also more p85-associated PI 3-kinase activity in these
      adipocytes. There was no difference in expression in the p85 regulatory subunit
      or the p110-alpha catalytic subunit of PI 3-kinase. In contrast, there was a
      sixfold reduction in the p110-beta catalytic subunit of PI 3-kinase in adipocytes
      from low-protein animals. These results suggest that poor fetal nutrition during
      pregnancy and lactation can have long-term effects on glucose transport and on
      the expression of key components of the insulin signaling pathway in adipocytes.

PMID- 9252479
TI  - Modulation of gliquidone action by forskolin in the pancreas of normal and GK
      rats.
AB  - This study aims to investigate whether agents that stimulate adenosine 3',5'
      cyclic monophosphate (cAMP) formation could be used to increase insulin release
      evoked by hypoglycemic sulfonylureas in non-insulin-dependent diabetes mellitus.
      For this purpose, the effect of gliquidone (1.0 microM) on insulin and glucagon
      release was examined in the perfused pancreas of either normal or Goto-Kakizaki
      (GK) rats at a low concentration of D-glucose (2.8 mM) and in the absence or
      presence of forskolin (1.3 microM). In normal rats, the diterpene exerted
      relatively little effect on basal insulin release but markedly augmented the
      insulinotropic action of gliquidone. In GK rats, forskolin dramatically augmented
      both basal and gliquidone-stimulated insulin output. In mirror image of its
      effect on insulin release, forskolin augmented basal glucagon output and failed
      to increase the secretory response of the A cell to gliquidone, at least in
      normal rats. On the contrary, in GK rats, forskolin, while slightly enhancing
      basal glucagon output, unmasked the glucagonotropic potential of gliquidone that
      was otherwise not detected in the diabetic animals. These findings are
      interpreted in light of a dual metabolic and energy-independent response of islet
      cells to the forskolin-induced generation of cAMP. They document the
      optimalization by endogenous cAMP of the B cell secretory response to gliquidone
      in non-insulin-dependent diabetes.

PMID- 9252480
TI  - Molecular analysis of insulin resistance in isolated ventricular cardiomyocytes
      of obese Zucker rats.
AB  - Isolated ventricular cardiomyocytes obtained from lean and genetically (fa/fa)
      obese Zucker rats were used to correlate alterations of insulin-induced glucose
      transport activation and GLUT-4 translocation to possible defects of the insulin
      signaling cascade. Maximal stimulation with insulin was found to produce an
      unaltered translocation of GLUT-4 to the plasma membrane (4.2- and 3.7-fold
      increase for lean and obese rats, respectively). However, a largely reduced
      sensitivity of 3-O-methylglucose transport could be detected in obese rats at
      physiological doses of insulin (completely unresponsive at 8 x 10(-11) M compared
      with 3-fold stimulation of glucose transport in lean controls). Tyrosine
      phosphorylation of the insulin receptor beta-subunit and the insulin receptor
      substrate 1 (IRS-1) was stimulated identically in cardiomyocytes from both lean
      and obese rats. Labeling of cells with [33P]orthophosphate revealed a marked
      increase in the serine and/or threonine phosphorylation of IRS-1 in the obese
      group (370% of lean controls), with a concomitant reduction in IRS-1 abundance
      (30-40%). The reduced sensitivity of glucose transport at 8 x 10(-11) M insulin
      was then found to correlate to a completely blunted response of IRS-1-associated
      phosphatidylinositol 3-kinase activity in cardiomyocytes from obese rats. Those
      data show that cardiac insulin resistance of obesity involves defective insulin
      signaling at low concentrations of the hormone, whereas GLUT-4 translocation is
      fully operative in the isolated cell. It is suggested that hyperphosphorylation
      of IRS-1 may significantly contribute to the pathogenesis of insulin resistance
      in the heart.

PMID- 9252481
TI  - Glucose transporter expression in L6 muscle cells: regulation through insulin-
      and stress-activated pathways.
AB  - We addressed the effect of long-term treatment with insulin, 2,4-dinitrophenol
      (DNP; an uncoupler of oxidative phosphorylation that increases energy demand) and
      300 mM mannitol (hyperosmolarity) on glucose transporter (GLUT) expression in L6
      muscle cells and the signaling pathways involved. We found the following. 1) The
      insulin-mediated increase in GLUT-1 is 70-kDa ribosomal protein S6 kinase (p70 S6
      kinase) and p38 mitogen-activated protein kinase (MAPK) dependent but
      extracellular signal-regulated protein kinase (ERK) and MAPK/ERK kinase (MEK)
      independent. The hypertonicity-stimulated elevation in GLUT-1 is p70 S6 kinase,
      p38 MAPK, and MEK dependent yet ERK independent. DNP also increased GLUT-1
      protein but did not depend on any of the above pathways, 2) Insulin increased
      GLUT-3 protein in a p70 S6 kinase-independent but MEK/ERK-dependent fashion.
      Inhibition of p38 MAPK potentiated the effect of insulin on GLUT-3. Hypertonicity
      increased GLUT-3 via p70 S6 kinase- and p38 MAPK-dependent pathways. In
      conclusion, we have dissected the molecular mechanisms used by insulin and
      hypertonicity that culminate in the induction of GLUT-1 and GLUT-3. The
      mechanism(s) used by DNP remains unknown.

PMID- 9252482
TI  - Intestinal growth-promoting properties of glucagon-like peptide-2 in mice.
AB  - Glucagon-like peptide-2 (GLP-2) has been shown to promote intestinal epithelial
      proliferation. We studied crypt cell proliferation, enterocyte cell death, and
      feeding behavior in GLP-2-treated mice. GLP-2 had no effect on food consumption
      [7.7 +/- 0.3 vs. 8.0 +/- 0.4 g/day, saline (control) vs. GLP-2-treated mice, P =
      not significant]; however, GLP-2 increased the crypt cell proliferation rate
      (46.0 +/- 1 vs. 57 +/- 5%, control vs. GLP-2, P < 0.01) and decreased the
      enterocyte apoptotic rate (5.9 +/- 0.7 vs. 2.8 +/- 0.2% apoptotic cells, control
      vs. GLP-2, P < 0.05) in small bowel (SB) epithelium. GLP-2 induced a significant
      increase in SB weight (1.3- to 1.75-fold increase over control, P < 0.05 to P <
      0.001) in mice 1-24 mo of age. Increased SB weight was maintained after daily
      administration of GLP-2 to mice for 12 wk, and cessation of GLP-2 administration
      in older mice led to regression of (increased) SB weight and mucosal height.
      These observations suggest that GLP-2 regulates both cell proliferation and
      apoptosis and promotes intestinal growth after both short- and long-term
      administration in vivo.

PMID- 9252483
TI  - Prolonged submaximal eccentric exercise is associated with increased levels of
      plasma IL-6.
AB  - To study the relationship between exercise-related muscle proteolysis and the
      cytokine response, a prolonged eccentric exercise model of one leg was used.
      Subjects performed two trials [a branched-chain amino acid (BCAA) supplementation
      and a control trial]. The release of amino acids from muscle during and after the
      eccentric exercise was decreased in the BCAA trial, suggesting a suppression of
      net muscle protein degradation. The plasma concentrations of interleukin (IL)-6
      increased from 0.75 +/- 0.19 (preexercise) to 5.02 +/- 0.96 pg/ml (2 h
      postexercise) in the control trial and in the BCAA supplementation trial from
      1.07 +/- 0.41 to 4.15 +/- 1.21 pg/ml. Eccentric exercise had no effect on the
      concentrations of neutrophils, lymphocytes, CD16+/CD56+, CD4+, CD8+, CD14+/CD38+,
      lymphocyte proliferative response, or cytotoxic activities. BCAA supplementation
      reduced the concentration of CD14+/CD38+ cells. This study shows that the
      concentration of IL-6 in plasma is increased after prolonged eccentric exercise
      and suggests that the cytokine response is independent of the muscle proteolysis
      that occur during exercise.

PMID- 9252484
TI  - Lactic acid potentiates bradykinin- and low-pH-induced release of CGRP from rat
      spinal cord slices.
AB  - Previous data from our laboratory have shown that calcitonin gene-related peptide
      (CGRP) is released into the circulation during pathogenesis of endotoxic,
      hemorrhagic, and septic shock and appears to mediate in part the vascular
      problems of shock. Elevations in the levels of bradykinin (BK) and lactic acid
      and lowering of tissue pH also occur during shock and could be involved in CGRP
      release. In the present study, we have tested whether lactic acid, alone or in
      combination with BK or low pH, triggers release of CGRP-like immunoreactivity
      (CGRP-LI) from sensory nerves, using rat spinal cord slices as a tissue model.
      Lowering media pH from 7.4 to < or = 6.0 increased the release of CGRP-LI. Lactic
      acid (5 and 10 mM) by itself elevated CGRP-LI release from a control of 6.89 +/-
      0.95 to 57.2 +/- 8.2 and 116 +/- 13 pg/mg protein, respectively. The combination
      of pH 6.0 and lactic acid (5 or 10 mM) caused more than additive stimulation of
      CGRP-LI release. BK (50 or 100 microM) elevated CGRP-LI release, which was
      greatly enhanced by lactic acid (2.5 or 5 mM). The data indicate that lactic acid
      potentiates BK- and low-pH-induced release of CGRP from sensory nerves in spinal
      cord. Similar mechanisms may occur at peripheral ends of sensory nerves,
      contributing to CGRP release during septic shock and other conditions with
      elevated lactic acid levels (e.g., strenuous exercise and tissue ischemia).

PMID- 9252485
TI  - Mixed muscle protein synthesis and breakdown after resistance exercise in humans.
AB  - Mixed muscle protein fractional synthesis rate (FSR) and fractional breakdown
      rate (FBR) were examined after an isolated bout of either concentric or eccentric
      resistance exercise. Subjects were eight untrained volunteers (4 males, 4
      females). Mixed muscle protein FSR and FBR were determined using primed constant
      infusions of [2H5]phenylalanine and 15N-phenylalanine, respectively. Subjects
      were studied in the fasted state on four occasions: at rest and 3, 24, and 48 h
      after a resistance exercise bout. Exercise was eight sets of eight concentric or
      eccentric repetitions at 80% of each subject's concentric 1 repetition maximum.
      There was no significant difference between contraction types for either FSR,
      FBR, or net balance (FSR minus FBR). Exercise resulted in significant increases
      above rest in muscle FSR at all times: 3 h = 112%, 24 h = 65%, 48 h = 34% (P <
      0.01). Muscle FBR was also increased by exercise at 3 h (31%; P < 0.05) and 24 h
      (18%; P < 0.05) postexercise but returned to resting levels by 48 h. Muscle net
      balance was significantly increased after exercise at all time points [(in %/h)
      rest = -0.0573 +/- 0.003 (SE), 3 h = -0.0298 +/- 0.003, 24 h = -0.0413 +/- 0.004,
      and 48 h = -0.0440 +/- 0.005], and was significantly different from zero at all
      time points (P < 0.05). There was also a significant correlation between FSR and
      FBR (r = 0.88, P < 0.001). We conclude that exercise resulted in an increase in
      muscle net protein balance that persisted for up to 48 h after the exercise bout
      and was unrelated to the type of muscle contraction performed.

PMID- 9252486
TI  - Regional lipolytic responses to isoproterenol in women.
AB  - We previously found that epinephrine, a mixed beta- and alpha-adrenoreceptor
      agonist, stimulates systemic and nonsplanchnic upper body free fatty acid (FFA)
      release but not lower body FFA release in healthy nonobese women. To evaluate the
      role of beta-adrenergic-mediated effects on this regional difference in
      lipolysis, we measured systemic, leg, and splanchnic FFA kinetics ([3H]palmitate)
      in seven healthy nonobese women before and during an intravenous isoproterenol
      infusion. Isoproterenol increased systemic palmitate flux (87 +/- 12 vs. 100 +/-
      10 mumol/min, P < 0.05) but failed to affect leg [10.8 +/- 1.2 vs. 11.4 +/- 2.3
      mumol/min, P = not significant (NS)] or splanchnic (10.8 +/- 3.2 vs. 10.0 +/- 1.8
      mumol/min, P = NS) palmitate release. Upper body nonsplanchnic palmitate release
      increased from 56 +/- 14 to 71 +/- 10 mumol/min. Systemic O2 consumption
      increased (227 +/- 11 to 241 +/- 10 ml/min, P = 0.006) during isoproterenol
      infusion, as did leg (318 +/- 42 vs. 404 +/- 53 ml/min, P < 0.01) and splanchnic
      (827 +/- 104 vs. 970 +/- 108 ml/min, P < 0.05) plasma flow. These results suggest
      that lower body adipose tissue lipolysis in women is less sensitive or responsive
      than nonsplanchnic upper body adipose tissue to beta-adrenergic stimulation and
      that regional differences in alpha 2-adrenergic-receptor responses were not
      responsible for the similar regional differences we observed previously with
      epinephrine.

PMID- 9252487
TI  - IGF-I regulation of Na(+)-K(+)-ATPase in rat arterial smooth muscle.
AB  - Insulin-like growth factor I (IGF-I) is vasodilatory and mitogenic for vascular
      smooth muscle cells (VSMC). Alteration in VSMC Na(+)-K(+)-adenosinetriphosphatase
      (Na(+)-K(+)-ATPase) activity is hypothesized to underlie abnormal vascular tone
      and growth in hypertension and diabetes. Therefore, we investigated effects of
      IGF-I on Na(+)-K(+)-ATPase activity in rat aortic VSMC. IGF-I increases pump
      activity in a dose- and time-dependent manner: the minimal dose required was 10(
      10) M, and the minimal time required was 20 min (at 10(-8) M) to increase
      activity. Similar effects persisted through 12 h. In Na(+)-loaded cells, IGF-I
      does not further stimulate activity. Blockade of Na+/H+ exchange attenuates IGF-I
      induced increases in activity after 30 min but has no effect after 12 h. Northern
      blot analyses reveal that expression of the alpha 1- and the alpha 2-subunits of
      the pump were unaffected by IGF-I. Plasma membrane alpha 1- and alpha 2-protein
      were also unaffected, suggesting translocation of preformed pools was not
      responsible for the increases. Inhibitors revealed that neither tyrosine kinase
      activity, RNA transcription, protein synthesis, nitric oxide synthase activity,
      or protein kinase C activity mediated this IGF-I effect. Therefore, IGF-I
      regulates Na pump activity in the short term by an Na+/H+ exchange-dependent but
      transcription/translocation-independent mechanism. These data suggest that IGF-I,
      known to be produced by VSMC, may regulate tone and growth responses abnormal in
      disease states such as hypertension and diabetes.

PMID- 9252488
TI  - An abundant supply of amino acids enhances the metabolic effect of exercise on
      muscle protein.
AB  - Six normal untrained men were studied during the intravenous infusion of a
      balanced amino acid mixture (approximately 0.15 g.kg-1.h-1 for 3 h) at rest and
      after a leg resistance exercise routine to test the influence of exercise on the
      regulation of muscle protein kinetics by hyperaminoacidemia. Leg muscle protein
      kinetics and transport of selected amino acids (alanine, phenylalanine, leucine,
      and lysine) were isotopically determined using a model based on arteriovenous
      blood samples and muscle biopsy. The intravenous amino acid infusion resulted in
      comparable increases in arterial amino acid concentrations at rest and after
      exercise, whereas leg blood flow was 64 +/- 5% greater after exercise than at
      rest. During hyperaminoacidemia, the increases in amino acid transport above
      basal were 30-100% greater after exercise than at rest. Increases in muscle
      protein synthesis were also greater after exercise than at rest (291 +/- 42% vs.
      141 +/- 45%). Muscle protein breakdown was not significantly affected by
      hyperminoacidemia either at rest or after exercise. We conclude that the
      stimulatory effect of exogenous amino acids on muscle protein synthesis is
      enhanced by prior exercise, perhaps in part because of enhanced blood flow. Our
      results imply that protein intake immediately after exercise may be more anabolic
      than when ingested at some later time.

PMID- 9252489
TI  - The somatotropic axis in neonatal calves can be modulated by nutrition, growth
      hormone, and Long-R3-IGF-I.
AB  - Effects on the somatotropic axis [plasma levels of insulin-like growth factors
      (IGFs) I and II, IGF-binding proteins (IGFBPs), and growth hormone (GH)] of
      feeding different amounts of colostrum or milk replacer, of Long-R3-IGF-I
      (administered subcutaneously or orally; 50 micrograms.kg body wt-1.day-1 for 7
      days), and of subcutaneously injected recombinant bovine GH (rbGH; 1 mg.kg body
      wt-1.day-1 for 7 days) were evaluated in calves during the 1st wk of life. Plasma
      Long-R3-IGF-I increased after subcutaneous application but not with the oral
      dose. Endogenous IGF-I was higher in calves fed colostrum six times compared with
      those fed only milk replacer. Native IGF-I was highest in rbGH-injected calves
      but was lowered by the subcutaneous injection of Long-R3-IGF-I. IGF-II
      concentrations were not modified by any of the treatments. IGFBP-2 increased in
      calves fed only milk replacer and those receiving subcutaneous Long-R3-IGF-I. GH
      was not modulated by differences in nutrition but increased after rbGH
      administration and similarly in all groups after intravenous injection of GH
      releasing factor analog GRF-(1-29). Parenteral administration of Long-R3-IGF-I
      decreased GH concentration but did not affect the secretory pattern. The data
      demonstrate that the somatotrophic axis is basically functioning in neonatal
      calves and is influenced by nutrition, GH, and Long-R3-IGF-I.

PMID- 9252490
TI  - In vivo NMR investigation of intramuscular glucose metabolism in conscious rats.
AB  - In vivo 13C nuclear magnetic resonance (NMR) spectroscopy was used to determine
      quantitatively the flux of muscle glycolysis, glycogen synthesis, pyruvate
      dehydrogenase, and pyruvate carboxylation in the hindlimb of conscious rats. 13C
      NMR spectroscopy was used to observe [1-13C]glucose label precursor incorporation
      into intramuscular [1-13C]glycogen, [3-13C]lactate, and [3-13C]alanine during a
      hyperglycemic (approximately 11 mM)-hyperinsulinemic (10 mU.kg-1.min-1) clamp.
      The glycogen synthesis rate was calculated to be 224 +/- 23 nmol.g-1.min-1. The
      kinetic data obtained from the label turnover in the intramuscular C-3 lactate
      and C-3 alanine metabolite pools, as well as in plasma C-3 lactate and C-3
      alanine, were combined with a steady-state rate analysis to determine the
      glycolytic flux (67.4 +/- 10.1 nmol.g-1.min-1). Steady-state isotopomer analysis
      of glutamate and pyruvate in skeletal muscle tissue extracts was used to
      determine the anaplerotic contribution of substrate via pyruvate carboxylation
      (Vpc). The pyruvate dehydrogenase flux (Vpdh) was calculated after a steady-state
      flux correction for Vpc. Calculated values of Vpc and Vpdh were 24.8 +/- 4.3 and
      110.0 +/- 18.7 nmol.g-1.min-1, respectively. In addition, [2-13C]acetate was used
      in a separate study to determine that pyruvate carboxylation was the major
      pathway for anaplerosis in skeletal muscle under conditions of hyperglycemia
      hyperinsulinemia.

PMID- 9252491
TI  - Exercise blunts declines in lipolysis and fat oxidation after dietary-induced
      weight loss in obese older women.
AB  - Weight loss (WL) by hypocaloric diet decreases adipocyte lipolysis and fat
      oxidation, adaptations that might predispose individuals to regain weight. Our
      hypothesis was that the addition of endurance exercise (EX) to dietary-induced WL
      (6 mo; 250-350 kcal/day deficit) would prevent declines in abdominal (ABD) and
      gluteal (GLT) adipocyte lipolysis and fat oxidation in obese older women. At
      baseline, the WL (n = 9) and WL+EX (n = 11) groups had similar body composition,
      fat distribution, aerobic fitness (VO2max), and resting fat metabolism.
      Reductions in body weight (WL = 11%, WL+EX = 8%), percent body fat, and intra
      abdominal fat area with the interventions were similar in both groups, but VO2max
      increased (9%, P < 0.01) only in the WL+EX group. Basal and adrenergic receptor-
      and postreceptor-stimulated lipolysis in ABD and GLT adipocytes decreased (20
      70%, P < 0.05) in the WL group but did not change in the WL+EX group. Fat
      oxidation decreased (38%, P < 0.05) in the WL group but not in the WL+EX group.
      The changes in fat oxidation and GLT lipolysis differed significantly between
      groups. Fat oxidation correlated positively with ABD and GLT adipocyte basal
      lipolysis at baseline (r = 0.45 and r = 0.53, P < 0.05), and the changes in fat
      oxidation with the interventions correlated positively with changes in ABD and
      GLT adipocyte basal lipolysis (r = 0.50 and r = 0.42. P < 0.05) in the entire
      group of women. These results indicate that exercise counteracts the decline in
      fat oxidation with WL, in part by maintaining adipocyte lipolytic responsiveness
      in some weight-reduced postmenopausal women.

PMID- 9252492
TI  - Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical
      organ and anterior pituitary.
AB  - We studied angiotensin II (ANG II) receptor subtype expression in selected brain
      nuclei and pituitary gland after water deprivation by in vitro receptor
      autoradiography using 125I-labeled [Sar1]ANG II and by in situ hybridization
      using 35S-labeled AT1A, AT1B, and AT2 receptor-specific riboprobes. In control
      rats we found binding to AT1 receptors in the subfornical organ, paraventricular
      nucleus, median eminence, and anterior pituitary; AT1A mRNA expression in the
      subfornical organ and paraventricular nucleus; and AT1B mRNA expression in the
      anterior pituitary. No receptor mRNA was found in the median eminence. AT1
      receptors and AT1A receptor mRNA levels were increased in the subfornical organ,
      and, in the anterior pituitary, AT1 receptors and AT1B receptor mRNA were
      increased, only after 5 days of water deprivation. No significant changes
      occurred after 1 or 3 days of water deprivation, and no regulation of ANG II
      receptor expression was detected in other brain areas. Our results show that
      prolonged water deprivation selectively regulates AT1 receptor expression and
      AT1A and AT1B receptor mRNA levels in the subfornical organ and anterior
      pituitary, respectively, supporting a role for these receptors during sustained
      dehydration.

PMID- 9252493
TI  - Increased sciatic nerve blood flow in diabetic rats: assessment by "molecular"
      vs. particulate microspheres.
AB  - Sciatic nerve blood flow in diabetic rats in typically increased or unchanged
      when assessed by the reference sample microsphere method in our laboratory. In
      contrast, blood flow is generally reported to be decreased approximately 50% when
      assessed with laser Doppler flowmetry or hydrogen clearance polarography. To
      address concerns that increased blood flow observed with microspheres might be
      anomalous because of their particulate nature and/or because insufficient numbers
      of microspheres are captured in the nerve, a plasma-soluble "molecular
      microsphere" ([3H]desmethylimipramine, mol wt = 266) and 11.3-micron 153Gd
      labeled microspheres were injected sequentially to assess blood flow in rats with
      streptozotocin diabetes of 2-4 wk duration. Nerve blood flows in diabetic rats
      were increased 1.5- to 2-fold (vs. control rats) with both tracers; these
      increases were prevented by tolrestat, an inhibitor of aldose reductase. These
      observations indicate that blood flow in sciatic nerve (like that in retina and
      kidney) is increased early after the onset of diabetes and is 1) demonstrable
      with a plasma-soluble tracer as well as with particulate microspheres and 2)
      linked to increased metabolism of glucose via the sorbitol pathway.

PMID- 9252494
TI  - Diabetes impairs sciatic nerve hyperemia induced by surgical trauma: implications
      for diabetic neuropathy.
AB  - The most widely used methods to assess nerve blood flow in diabetics rats are
      hydrogen clearance polarography and laser Doppler flowmetry, techniques requiring
      surgical exposure of the nerve. In these experiments, we examined the hypothesis
      that the trauma of surgical exposure introduces an important and hitherto largely
      unrecognized variable that could account for discordant reports on nerve blood
      flow changes induced by diabetes. We used the noninvasive (for sciatic nerve)
      reference sample microsphere method to quantify sciatic nerve blood flow in
      unexposed va. surgically exposed nerves in rats with streptozotocin-induced
      diabetes (at different temperatures and after curarization) and in unexposed vs.
      surgically exposed nerves in galactose-fed rats. Baseline resting blood flow in
      unexposed nerves in both animal models of diabetes was either normal or increased
      (but was decreased in diabetic rats given d-tubocurarine). Furthermore, the
      normal brisk hyperemic nerve blood flow response to the minimal trauma associated
      with surgical exposure of the nerve was markedly impaired in diabetic and in
      galactose-fed rats. Normalization of the blood flow response to trauma in
      galactose-fed rats by an aldose reductase inhibitor suggests that the impairment
      is linked to increased polyol pathway metabolism. These findings 1) confirm our
      previous findings that sciatic nerve blood flow in diabetic rats is increased or
      unchanged in unexposed nerves, while also confirming reports that in surgically
      exposed nerves blood flow is higher in control than in diabetic rats, and 2)
      indicate that blood flows in surgically exposed nerves are largely a measure of
      vascular responses to injury rather than (patho)physiological blood flow in
      undisturbed nerves.

PMID- 9252495
TI  - Differential effects of lipoic acid stereoisomers on glucose metabolism in
      insulin-resistant skeletal muscle.
AB  - The racemic mixture of the antioxidant alpha-lipoic acid (ALA) enhances insulin
      stimulated glucose metabolism in insulin-resistant humans and animals. We
      determined the individual effects of the pure R-(+) and S-(-) enantiomers of ALA
      on glucose metabolism in skeletal muscle of an animal model of insulin
      resistance, hyperinsulinemia, and dyslipidemia: the obese Zucker (fa/fa) rat.
      Obese rats were treated intraperitoneally acutely (100 mg/kg body wt for 1 h) or
      chronically [10 days with 30 mg/kg of R-(+)-ALA or 50 mg/kg of S-(-)-ALA].
      Glucose transport [2-deoxyglucose (2-DG) uptake], glycogen synthesis, and glucose
      oxidation were determined in the epitrochlearis muscles in the absence or
      presence of insulin (13.3 nM). Acutely, R-(+)-ALA increased insulin-mediated 2-DG
      uptake by 64% (P < 0.05), whereas S-(-)-ALA had no significant effect. Although
      chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free
      fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA
      treatment further increased insulin (15%) and had no effect on FFA. Insulin
      stimulated 2-DG uptake was increased by 65% by chronic R-(+)-ALA treatment,
      whereas S-(-)-ALA administration resulted in only a 29% improvement. Chronic R
      (+)-ALA treatment elicited a 26% increase in insulin-stimulated glycogen
      synthesis and a 33% enhancement of insulin-stimulated glucose oxidation. No
      significant increase in these parameters was observed after S-(-)-ALA treatment.
      Glucose transporter (GLUT-4) protein was unchanged after chronic R-(+)-ALA
      treatment but was reduced to 81 +/- 6% of obese control with S-(-)-ALA treatment.
      Therefore, chronic parenteral treatment with the antioxidant ALA enhances insulin
      stimulated glucose transport and non-oxidative and oxidative glucose metabolism
      in insulin-resistant rat skeletal muscle, with the R-(+) enantiomer being much
      more effective than the S-(-) enantiomer.

PMID- 9252496
TI  - Constant infusion and bolus injection of stable-label tracer give reproducible
      and comparable fasting HGO.
AB  - We have investigated the reproducibility of fasting hepatic glucose output (HGO)
      estimates by use of isotope dilution methodology of stable-label tracers. Six
      normal subjects were studied on two occasions 1 wk apart. After an overnight
      fast, the subjects received a bolus injection of 7 mg/kg of [U-13C]glucose and,
      simultaneously, a primed constant infusion of 0.05 mg.kg-1.min-1 of [6,6(
      2)H]glucose. The bolus injection provided one estimate of HGO (HGOBOL), and the
      constant infusion provided two estimates of HGO, namely, HGO at 2 h (HGOINF2) and
      HGO at 4 h (HGOINF4), both with the assumption of steady-state conditions. All
      estimates were similar in value; HGOBOL was highest, followed by HGOINF2 and
      HGOINF4 [2.30 +/- 0.11 (SE), 2.17 +/- 0.12, and 2.01 +/- 0.13 mg.kg-1.min-1]. The
      constant infusion gave highly reproducible results. In the case of HGOINF2, the
      within-subject coefficient of variation (CV) was only 3% compared with 5% of
      HGOINF4. The reproducibility of HGOBOL was comparable with the within-subject CV
      of 7%. We conclude that a constant infusion and a bolus injection of stable-label
      tracer give reproducible and comparable estimates of HGO.

PMID- 9252497
TI  - Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate
      nucleus damage.
AB  - Leptin is a protein secreted by adipocytes that is important in regulating
      appetite and adiposity. Recent studies have suggested the presence of leptin
      receptors in the arcuate nucleus of the hypothalamus (ANH). Neonatal
      administration of monosodium glutamate (MSG) damages the ANH, resulting in
      obesity and neuroendocrine dysfunction. Neonatal administration of MSG was
      utilized to test the hypothesis that the anatomic site for many of leptin's
      actions is the ANH. Female control (n = 6) and MSG-treated rats (n = 7) were
      implanted for 14 days with osmotic minipumps containing phosphate-buffered saline
      or leptin (1 mg.kg-1.day-1). Leptin suppressed (P < 0.05) body weight gain in
      controls but did not suppress weight gain in MSG-treated rats. Leptin decreased
      (P < 0.05) fat depots in controls but had no effect in MSG-treated rats. Night
      feeding was suppressed (P < 0.05) in leptin-treated control rats. MSG-treated
      rats showed a suppression in food intake that was of a smaller magnitude and
      appeared later in the course of leptin treatment. These findings suggest that
      leptin mediates some physiological actions related to fat mobilization via
      receptors located in the ANH.

PMID- 9252498
TI  - Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in
      adult and suckling rats.
AB  - A polyclonal affinity-purified antibody to the carboxyl-terminal end of the rat
      monocarboxylate transporter 1 (MCT1) was generated in chickens and used in
      immunocytochemical studies of brain tissue sections from adult and suckling rats.
      The antibody identified a 48-kDa band on immunoblots and stained tissue sections
      of heart, cecum, kidney, and skeletal muscle, consistent with the reported
      molecular mass and cellular expression for this transporter. In tissue sections
      from adult brains, the antibody labeled brain microvessel endothelial cells,
      ependymocytes, glial-limiting membranes, and neuropil. In brain sections from 3-
      to 14-day-old rats, microvessels were much more strongly labeled and neuropil was
      weakly labeled compared with sections from adults. Immunoelectron microscopy
      indicated that labeling was present on both luminal and abluminal endothelial
      cell plasma membranes. These results suggest that MCT1 may play an important role
      in the passage of lactate and other monocarboxylates across the blood-brain
      barrier and that suckling rats may be especially dependent on this transporter to
      supply energy substrates to the brain.

PMID- 9252499
TI  - Nociceptin, a novel endogenous ligand for the ORL1 receptor, has potent erectile
      activity in the cat.
AB  - The heptadecapeptide nociceptin, also known as orphanin FQ, is a newly discovered
      endogenous ligand for the opioid-like G protein-coupled receptor ORL1. The
      present study was undertaken to investigate the effects of intracavernosal
      injections of nociceptin on penile erection in anesthetized cats. Responses to
      nociception were compared with erectile responses elicited by intracavernosal
      injection of vasoactive intestinal polypeptide (VIP), adrenomedullin (ADM), the
      novel nitric oxide donor diethylaminenitric oxide complex sodium (DEA/NO), and
      the control triple-drug combination (papaverine, phentolamine, and prostaglandin
      E1). The order of potency was VIP > ADM > nociceptin > DEA/NO. Intracavernosal
      injections of nociceptin in doses of 0.3-30 nmol elicited dose-related increases
      in cavernosal pressure and penile length that were comparable to those induced by
      the triple-drug combination, which is used in the treatment of erectile
      dysfunction. The response to nociceptin was rapid in onset, and the duration of
      the peak pressure increase and total response was significantly shorter than the
      response to the control triple-drug combination but longer in duration than
      responses to VIP and ADM. Intracavernosal injection of the triple-drug
      combination resulted in a greater decrease in mean systemic arterial blood
      pressure than did nociceptin. These data demonstrate that intracavernosal
      injection of this novel endogenous ligand for the ORL1 receptor induces a potent
      and relatively long-lasting erectile response in the cat.

PMID- 9252500
TI  - Exercise-stimulated glucose transport in skeletal muscle is nitric oxide
      dependent.
AB  - It has been suggested that there are separate insulin-stimulated and contraction
      stimulated glucose transport pathways in skeletal muscle. This study examined the
      effects of nitric oxide on glucose transport in rat skeletal muscle by use of an
      isolated sarcolemmal membrane preparation and the nitric oxide synthase inhibitor
      N omega-nitro-L-arginine methyl ester (L-NAME), administered in the drinking
      water (1 mg/ml). Female Sprague-Dawley rats were divided into five groups:
      control, acute exercise, acute exercise+L-NAME, insulin stimulated, and insulin
      stimulated+L-NAME. Exercise (45 min of exhaustive treadmill running) increased
      glucose transport (37 +/- 2 to 76 +/- 5 pmol.mg-1.15 s-1) and this increase was
      completely inhibited by L-NAME (40 +/- 4 pmol.mg-1.15 s-1). A maximum dose of
      insulin increased glucose transport (87 +/- 10 pmol.mg-1.15 s-1), and adding L
      NAME had no effect (87 +/- 11 pmol.mg-1.15 s-1). In addition, exercise, but not
      exercise+L-NAME, increased sarcolemma GLUT-4 content. This study confirms that
      there are separate pathways for contraction- and insulin-stimulated glucose
      transport. More importantly, although exercise and insulin both significantly
      increased glucose transport, L-NAME had no effect on insulin-stimulated glucose
      transport but blocked the exercise-stimulated transport. We conclude that nitric
      oxide is involved in the signal transduction mechanism to increase glucose
      transport during exercise.

PMID- 9252501
TI  - Leptin increases uncoupling protein expression and energy expenditure.
AB  - In ob/ob mice, leptin increases energy expenditure and sympathetic outflow to
      brown adipose tissue (BAT). To test whether the mechanism of increased energy
      expenditure may involve increased thermogenesis in BAT, we acclimated normal rats
      to thermoneutrality for 2 wk followed by leptin administration for 1 wk. Some
      rats were food restricted for 1 wk to the level of food consumption in the leptin
      treated ad libitum-fed rats, and the same rats were both food restricted and
      administered leptin for a second week. We examined oxygen consumption and
      uncoupling protein (UCP) expression in BAT. Leptin increased oxygen consumption
      after the 5th and 6th days in ad libitum-fed rats and after the 4th, 5th, and 6th
      days in food-restricted rats. Leptin increased BAT UCP mRNA levels greater than
      twofold in both ad libitum-fed and food-restricted rats. These data demonstrate a
      leptin-induced increase in energy expenditure in nonmutant rodents and suggest
      that one mechanism by which leptin increases energy expenditure is through
      increased thermogenesis in BAT, including increased expression of UCP.

PMID- 9252502
TI  - Critical fatness hypothesis.

PMID- 9252503
TI  - Epithelial cell growth and differentiation. I. Intestinal growth factors.

PMID- 9252504
TI  - GSH transport in mitochondria: defense against TNF-induced oxidative stress and
      alcohol-induced defect.
AB  - Mitochondria generate reactive oxygen species (ROS) as byproducts of molecular
      oxygen consumption in the electron transport chain. Most cellular oxygen is
      consumed in the cytochrome-c oxidase complex of the respiratory chain, which does
      not generate reactive species. The ubiquinone pool of complex III of respiration
      is the major site within the respiratory chain that generates superoxide anion as
      a result of a single electron transfer to molecular oxygen. Superoxide anion and
      hydrogen peroxide, derived from the former by superoxide dismutase, are precursor
      of hydroxyl radical through the participation of transition metals. Glutathione
      (GSH) in mitochondria is the only defense available to metabolize hydrogen
      peroxide. A small fraction of the total cellular GSH pool is sequestered in
      mitochondria by the action of a carrier that transports GSH from the cytosol to
      the mitochondrial matrix. Mitochondria are not only one of the main cellular
      sources of ROS, they also are a key target of ROS. Mitochondria are subcellular
      targets of cytokines, especially tumor necrosis factor (TNF); depletion of GSH in
      this organelle renders the cell more susceptible to oxidative stress originating
      in mitochondria. Ceramide generated during TNF signaling leads to increased
      production of ROS in mitochondria. Chronic ethanol-fed hepatocytes are
      selectively depleted of GSH in mitochondria due to a defective operation of the
      carrier responsible for transport of GSH from the cytosol into the mitochondrial
      matrix. Under these conditions, limitation of the mitochondrial GSH pool
      represents a critical contributory factor that sensitizes alcoholic hepatocytes
      to the prooxidant effects of cytokines and prooxidants generated by oxidative
      metabolism of ethanol. S-adenosyl-L-methionine prevents development of the
      ethanol-induced defect. The mitochondrial GSH carrier has been functionally
      expressed in Xenopus laevis oocytes microinjected with mRNA from rat liver. This
      critical carrier displays functional characteristics distinct from other plasma
      membrane GSH carriers, such as its ATP dependency, inhibitor specificity, and the
      size class of mRNA that encode the corresponding carrier, suggesting that the
      mitochondrial carrier of GSH is a gene product distinct from the plasma membrane
      transporters.

PMID- 9252505
TI  - Determinants of triacylglycerol transport from the endoplasmic reticulum to the
      Golgi in intestine.
AB  - The ability of the intestinal cell to export triacylglycerol (TG) is a
      physiologically regulatable function. The intracellular site where this occurs is
      unknown, although available evidence suggests that the step between the
      endoplasmic reticulum (ER) and the Golgi is the most likely. We studied this
      process in rat enterocytes that were isolated from the proximal intestine. A
      novel system was developed in which [3H]TG was transported from ER to the Golgi.
      This process was time, ATP, temperature, and cytosol dependent. The cytosolic
      factor(s) was heat and trypsin sensitive. TG transport was directly proportional
      to the amount of added nonradiolabeled acceptor Golgi. The rate of TG transported
      to the Golgi was the fastest in cells isolated from rats that had been
      intraduodenally infused in vivo with glyceryltrioleate (TO) plus
      phosphatidylcholine and slowest in cells isolated from bile-fistulated rats
      infused with TO in vivo compared with cells from in vivo TO-infused, bile duct
      intact rats, mimicking the relative transport rates seen in vivo. TG transport in
      vitro could not be quenched by adding TG emulsions, chylomicrons, liposomes, or
      guanosine 5'-O-(3-thiotriphosphate). Cytosol from the liver and kidney supported
      TG transport, but the Golgi from liver or kidney did not accept TG from
      intestinal ER. We conclude that an intestinally specific, active transport
      mechanism transports TG from the ER to the Golgi and that this might be a
      regulatory step in TG export from the intestinal cell.

PMID- 9252506
TI  - Mechanisms mediating gastric hyperemic and acid responses to central TRH analog
      at a cytoprotective dose.
AB  - Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone
      (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were
      investigated, as well as the underlying mechanisms of the responses. Gastric acid
      secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance
      technique), and mucosal vascular resistance (GMVR) and mean arterial pressure
      (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng)
      administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/
      5.3 to 100.6 +/- 20.9 ml.min-1.100 g-1 and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9
      mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml-1.min.100 g,
      whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mumol/30
      min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368
      were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In
      rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide
      (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or
      decrease GMVR but did stimulate GAS. These data show that vagal stimulation by
      the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose
      increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin
      sensitive afferent fibers, whereas acid secretion is under the inhibitory
      influence of prostaglandins and CGRP.

PMID- 9252507
TI  - Characterization of ion transport mechanisms regulating intracellular pH in
      hepatic stellate cells.
AB  - The aim of this study was to evaluate intracellular pH (pHi) regulation in
      nonactivated and activated rat hepatic stellate cells (HSC). The fluorescent pHi
      indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein was used to measure pHi
      in the presence and absence of HCO3-. In the absence of HCO3-, baseline pHi was
      significantly higher (P < 0.001) in activated than in nonactivated HSC (7.1 +/-
      0.1 vs. 6.9 +/- 0.2) and decreased, in both groups, after amiloride
      administration and after Na+ removal. After an acid-loading maneuver, pHi
      recovery was significantly higher (P < 0.03) in activated than in nonactivated
      HSC (H+ flux = 11.0 +/- 3.8 vs. 7.7 +/- 2.9 mM/min at pHi 6.6) and was inhibited
      by amiloride and Na+ removal. In the presence of HCO3-, baseline pHi was higher
      in both groups and decreased after amiloride administration. Amiloride and Na+
      removal inhibited pHi recovery after an intracellular acid load by 77 and 93%,
      respectively, in nonactivated and by 82 and 92%, respectively, in activated HSC,
      whereas 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibited pHi recovery
      by only 27%. Acute Cl- removal increased pHi by 0.07 +/- 0.01 pH unit/min in the
      absence but not in the presence of 4,4'-diisothiocyanostilbene-2,2'-disulfonic
      acid in nonactivated and activated HSC in an Na(+)-independent manner. In
      activated HSC, 24 h of incubation with 25 ng/ml platelet-derived growth factor
      (PDGF)-BB (in 0.5% serum) did not modify baseline pHi (7.07 +/- 0.1 vs. 7.08 +/-
      0.1 in HSC cultured in 0.5% serum only) but significantly (P < 0.02) increased,
      with respect to controls, pHi recovery after an acute acid load. Incubation with
      PDGF for 24 h induced a fivefold increase in HSC proliferation expressed as
      percentage of bromodeoxyuridine-positive cells (30.8 +/- 6.7 vs. 6.1 +/- 1.9% in
      controls). When amiloride (0.1 mM) was present, PDGF-induced HSC proliferation
      was significantly inhibited (8.1 +/- 0.4%, P < 0.001). Our results show that 1)
      the Na+/H+ exchanger is the main pHi regulator in rat HSC, 2) activation of HSC
      is associated with an increase in pHi and in the activity of the Na+/H+
      exchanger, 3) PDGF increases the activity of this exchanger, and 4) amiloride is
      able to inhibit HSC proliferation induced by PDGF.

PMID- 9252508
TI  - Synaptic inputs to morphologically identified myenteric neurons in guinea pig
      rectum from pelvic nerves.
AB  - Neurobiotin-filled microelectrodes were used to investigate electrical and
      synaptic behavior and morphological characteristics of rectal myenteric neurons
      that received synaptic inputs from the pelvic nerves. Stimulation of the pelvic
      nerve at low frequencies (< 3.3 Hz) evoked nicotinic fast excitatory postsynaptic
      potentials (fast EPSPs) in 45.3% of rectal neurons. Pelvic fast EPSPs were found
      in S/type 1, AH/type 2, type 3, or single-spike neurons that had a single long
      process preferentially projecting in the orad direction. Stimulation of the
      pelvic nerve at higher frequencies (5-20 Hz) elicited slow membrane excitation in
      13.9% of the neurons. They were either AH/type 2 neurons with Dogiel II
      morphology or S/type 1 neurons with a single long process. Hexamethonium (100
      microM) blocked pelvic fast EPSPs more quickly than those evoked by fiber tract
      stimulation but did not affect slow excitatory response. The results suggested
      the presence of more than one nicotinic-cholinergic synapse in the pelvic nerve
      pathway and the possible release of a noncholinergic excitatory substance from
      the afferent nerve terminals. It is possible that a subpopulation of rectal
      neurons, which receive a fast EPSP and have a single long process that projects
      in the orad direction, might be interneurons that mediate the defecation reflex.

PMID- 9252509
TI  - P-selectin-deficient mice are protected from PAF-induced shock, intestinal
      injury, and lethality.
AB  - In a previous study, we showed that anti-CD11b or anti-CD18 antibody markedly
      attenuated platelet-activating factor (PAF)-induced shock and intestinal necrosis
      in rats, whereas anti-P-selectin anti-body was ineffective. Here we used
      genetically altered mice to study the mechanism of PAF in mice. We found that P
      selectin-deficient mice are completely protected from the adverse effects of PAF
      with no mortality or intestinal injury and only mild hemoconcentration and
      transient hypotension. In contrast, CD18- or intercellular adhesion molecule 1
      (ICAM-1)-deficient mice were not protected from PAF-induced tissue injury and
      death. However, when ICAM-1-, but not CD18-, deficient mice were pretreated with
      fucoidin, the adverse effects of PAF were markedly reduced; survival was 100%,
      although hypotension still developed. Neutrophil-depleted mice were protected
      from PAF-induced intestinal injury but still developed hypotension and
      hemoconcentration. PAF increases peripheral blood neutrophil counts, probably by
      inducing granulopoiesis, since neutrophil-depleted mice still showed
      granulocytosis 60 min after PAF. Thus P-selectin plays an important role in PAF
      induced injury in mice, and the selectins and the integrin-ICAM-1 system work in
      concert to mediate the inflammatory response to PAF in vivo.

PMID- 9252510
TI  - Ontogeny and location of HMG-CoA reductase, ACAT, and MGAT in human small
      intestine.
AB  - Because a few enzymes are in most tissues, enabling them to produce lipids
      necessary for growth and differentiation, the development of their activity in
      the intestine, an important organ of fat transport and metabolism, is of great
      interest. In this investigation, the ontogeny and location of 3-hydroxy-3
      methylglutaryl CoA (HMG-CoA) reductase (the key regulatory enzyme in the
      cholesterol pathway), acyl-CoA:cholesterol acyltransferase (ACAT; responsible for
      cholesterol esterification), and monoacylglycerol acyltransferase (MGAT; the more
      representative enzyme of the neutral lipid pathway) were examined in the human
      fetal small intestine. The developing gut exhibited high levels (pmol.mg-1.min-1)
      of HMG-CoA reductase (7.65 +/- 0.35), ACAT (16.98 +/- 1.12), and MGAT (689.74 +/-
      37.54). Significant positive correlations were recorded between fetal age (8-22
      wk) and the enzyme activities of HMG-CoA reductase in the proximal (P < 0.005)
      and middle (P < 0.01) segments, ACAT in the distal segment (P < 0.03), and MGAT
      in the proximal segment (P < 0.03) of the gut. Age-specific changes were found in
      the location of the three enzymes in the contiguous intestinal segments that were
      investigated. We concluded that the fetal small intestine has substantial HMG-CoA
      reductase, ACAT, and MGAT activity, which displays specific patterns during
      development.

PMID- 9252511
TI  - 5-HT-induced colonic contractions: enteric locus of action and receptor subtypes.
AB  - The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the
      receptor subtypes involved in the stimulation of in vivo phasic contractions in
      the colon were investigated by close intra-arterial infusions in conscious dogs.
      The contractile response to 5-HT was blocked completely by prior close intra
      arterial infusion of atropine and reduced significantly by prior close intra
      arterial infusions of tetrodotoxin and hexamethonium. The contractile response
      was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior
      close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior
      close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4
      receptor antagonists had no significant effect on the contractile response to 5
      HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently
      inhibited the contractile response to 5-HT. We conclude that the in vivo phasic
      contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors
      located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may
      also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that
      use NO as a neurotransmitter.

PMID- 9252512
TI  - Enterocytes are the primary source of the chemokine ENA-78 in normal colon and
      ulcerative colitis.
AB  - Epithelial cell-derived neutrophil-activating protein-78 (ENA-78) is a neutrophil
      directed C-X-C chemokine. We report that Caco-2 and T84 human intestinal
      epithelial cells produce ENA-78 after stimulation by interleukin (IL)-1 beta or
      tumor necrosis factor-alpha. Caco-2 cells show increased IL-8 production at 4-12
      h and increased ENA-78 production at 8-24 h after cytokine stimulation.
      Immunohistochemical studies in normal human colon and in ulcerative colitis
      demonstrate ENA-78 immunoreactivity principally associated with crypt epithelial
      cells. Furthermore, human colonic tissues from patients with ulcerative colitis
      show elevated levels of ENA-78 mRNA (24-fold increase, P < 0.01) and protein (4
      fold increase, P < 0.05) compared with normal controls. Thus ENA-78 is produced
      in normal colon and in ulcerative colitis and is predominantly of enterocyte
      origin. The kinetics of ENA-78 induction in human colon epithelial cell lines are
      delayed and prolonged compared with IL-8. We propose that ENA-78 and IL-8 serve
      complementary and sequential roles in neutrophil recruitment in ulcerative
      colitis. ENA-78 as an enterocyte-derived, neutrophil-activating chemokine may be
      especially important in neutrophil recruitment from the lamina propria into the
      epithelial layer.

PMID- 9252513
TI  - Developmental expression of SI is regulated in transgenic mice by an
      evolutionarily conserved promoter.
AB  - Developmental expression of the sucrase-isomaltase (SI) gene in the mouse
      intestine involves two major transitions that correspond to critical
      developmental events. Low levels of SI mRNA were first identified in day 16.5
      fetal mouse intestine, immediately after the transition from stratified endoderm
      to a columnar epithelium organized in nascent villi. Low levels were maintained
      until the third week of life, when induction of SI mRNA to adult levels was
      observed coincident with the time of weaning. The mechanism of this pattern of SI
      gene expression was studied in transgenic mice using a reporter gene construct
      containing an SI gene promoter that is evolutionarily conserved between mouse and
      human (nucleotides -201 to +54 of the mouse SI gene). This promoter included the
      necessary regulatory information to direct transcription to enterocytes in
      developmental and differentiation-dependent patterns that recapitulated the
      expression of the endogenous SI gene. However, transgenes lacked the ability to
      direct induction of precocious expression in suckling animals after
      administration of corticosteroids. These findings define a short SI gene promoter
      that contains cis-acting elements that are responsible for developmental and
      differentiation-dependent transcriptional regulation.

PMID- 9252514
TI  - Signal transduction pathways via guanylin and uroguanylin in stomach and
      intestine.
AB  - Guanylin and uroguanylin are peptides that activate receptor guanylate cyclases
      (GCs) and elicit increased intestinal secretion. Bacteria that cause traveler's
      diarrhea produce heat-stable toxins (STs) that mimic this action. Investigation
      of the distribution and identity of receptor GCs in the gastrointestinal tract of
      rats revealed that receptors were localized to epithelial cells in stomach and
      intestine. Clusters of cells in gastric mucosa and enterocytes lining the
      intestine exhibited specific binding of 125I-labeled ST. Ligated loops of stomach
      and intestine treated with intraluminal ST had significant increases in guanosine
      3',5'-cyclic monophosphate (cGMP), with duodenum exhibiting the greatest
      response. Expression of guanylate cyclase C (GCC) mRNA and a truncated, GCC-like
      mRNA was found in both stomach and intestine. Both mRNAs were isolated as cDNAs
      encoding the GC catalytic domain. The 0.9-kilobase (kb) cDNA is 99.8% identical
      to GCC, whereas the truncated, 0.75-kb GCC-like cDNA has a 159-nucleotide
      deletion and is 96.6% identical to GCC at the protein level. Uroguanylin and
      guanylin mRNAs were detected in stomach and intestine. Uroguanylin mRNA was most
      abundant in small intestine, whereas guanylin mRNA was highest in large
      intestine. Thus the stomach and intestine are targets for regulation of transport
      by guanylin and uroguanylin via cGMP.

PMID- 9252515
TI  - Reciprocal inhibitory paracrine pathways link histamine and somatostatin
      secretion in the fundus of the stomach.
AB  - The present study was designed to examine the functional linkage between
      histamine and somatostatin secretion in the fundus of the stomach. In segments of
      rat fundic mucosa, superfusion with thioperamide (H3 antagonist) increased
      somatostatin and decreased histamine secretion; superfusion with (R)(-)-alpha
      methylhistamine (H3 agonist) had the opposite effect, decreasing somatostatin and
      increasing histamine secretion. The pattern implied that endogenous histamine,
      acting via H3 receptors, exerts an inhibitory paracrine influence on somatostatin
      secretion. Superfusion with somatostatin antibody (1:250) increased histamine
      secretion, implying that endogenous somatostatin, in turn, exerts an inhibitory
      paracrine influence on histamine secretion. Somatostatin antibody also abolished
      the decrease in histamine secretion induced by thioperamide and the increase in
      histamine secretion induced by (R)(-)-alpha-methylhistamine, implying that
      changes in histamine secretion induced by activation of H3 receptors reflect
      changes in somatostatin secretion. Superfusion with the muscarinic agonist
      methacholine alone and in the presence of either H3 agonist or H3 antagonist
      confirmed the existence of reciprocal inhibitory pathways linking somatostatin
      and histamine. We conclude that fundic histamine and somatostatin secretion are
      linked via reciprocal inhibitory paracrine pathways that serve to amplify the
      regulatory influence of somatostatin.

PMID- 9252516
TI  - Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not
      inhibit acid secretion or motility.
AB  - The objectives of these studies were to examine whether the trefoil peptide
      porcine pancreatic spasmolytic polypeptide (PSP) had gastric mucosal protectant
      properties similar to its human equivalent human spasmolytic polypeptide (hSP)
      and to confirm the antisecretory and antimotility action of the peptide. PSP and
      recombinant hSP reduced gastric mucosal damage caused by a combination of
      subcutaneous indomethacin and restraint stress in the conscious rat. At a dose of
      500 micrograms/kg bolus plus 500 micrograms.kg-1.h-1 sc, PSP significantly
      reduced the total area of damage by 58%. PSP at a dose of 150 micrograms/kg iv
      had no inhibitory effect on pentagastrin-stimulated gastric acid secretion in the
      perfused stomachs of anesthetized rats. This lack of antisecretory activity was
      confirmed in vitro using an isolated stomach preparation from the immature rat.
      PSP and hSP at concentrations up to 800 nM did not inhibit electrically or
      chemically evoked contractions of the guinea pig ileum and duodenum in vitro.
      Thus antisecretory and antimotility actions do not underlie the mucosal
      protectant properties of PSP. PSP did, however, stimulate cell migration, and
      this may, at least in part, account for its protectant properties.

PMID- 9252517
TI  - Effect of cholecystokinin-A receptor blockade on lipid-induced gastric relaxation
      in humans.
AB  - The purpose of this study was to assess the role of endogenous cholecystokinin
      (CCK) in regulating fat-induced changes in human gastric relaxation. Proximal
      gastric pressure-volume relationships were determined in 12 healthy volunteers
      during a series of gastric distensions, both fasting and after intragastric
      instillation of 250 ml of 10% Intralipid. All subjects were studied twice, in a
      randomized, double-blind study, during intravenous infusion of either loxiglumide
      (CCK-A antagonist) or saline. For each distension, intragastric pressure and
      compliance were determined together with perception intensity. During saline
      infusion, Intralipid reduced intragastric pressure (prelipid, 11.7 +/- 0.8;
      postlipid, 9.7 +/- 0.6 mmHg; P = 0.002) and increased compliance (pressure-volume
      slope values: prelipid, 87.6 +/- 9.7; postlipid, 47.2 +/- 7; P < 0.01).
      Loxiglumide infusion during fasting exerted no effect on either intragastric
      pressure or compliance. After lipid, however, loxiglumide abolished the expected
      postlipid reduction in intragastric pressure (prelipid, 12.1 +/- 0.7; postlipid,
      11.5 +/- 0.8 mmHg; P = 0.4) but did not consistently abolish the postlipid
      increase in compliance. Loxiglumide exerted no effect on the cumulative
      perception score or on the volume at perception threshold, although it prevented
      the fat-induced reduction in pressure at perception threshold [control: prelipid,
      15.4 +/- 1.1; postlipid, 10.7 +/- 0.5 (P < 0.05); loxiglumide: prelipid, 13.8 +/-
      1.5; postlipid, 12.2 +/- 0.9 (P > 0.05)]. Endogenous CCK or CCK-A receptors
      therefore play a role in the fat-induced reduction of intragastric pressure and
      might also modulate gastric perception after lipid.

PMID- 9252519
TI  - Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells
      and in vivo.
AB  - Ursodeoxycholate (UDCA) has anti-inflammatory and chemoprotective effects in
      animal models of inflammatory bowel disease and colon cancer. Because
      overproduction of nitric oxide (NO) by the inducible isoform of NO synthase
      (iNOS) is implicated in the pathogenesis of these conditions, we investigated the
      ability of UDCA to inhibit NO production in transformed human intestinal
      epithelial (DLD-1) cells. Nitrite/nitrate production was measured by the Griess
      reaction, enzymatic activity of iNOS was assessed by conversion of L-arginine to
      L-citrulline, and protein and mRNA were measured by Western and Northern
      blotting. Dose-dependent inhibition of interleukin-1 beta- and interferon-gamma
      stimulated nitrite/nitrate production was observed when cells were preincubated
      for 6 h with UDCA (0-800 microM), and a substantial inhibition (81 +/- 3.2%) was
      seen at 500 microM. In cytokine-stimulated cells, UDCA reduced iNOS mRNA,
      protein, and enzyme activity without exerting cytotoxicity. UDCA had a minimal
      direct inhibitory effect on iNOS enzyme activity. UDCA pretreatment also reduced
      the expression of iNOS in the colonic epithelium of rats treated with bacterial
      lipopolysaccharide. Thus UDCA inhibits the induction of epithelial iNOS in vitro
      and in vivo, and this effect may contribute to the anti-inflammatory and
      chemoprotective actions of UDCA.

PMID- 9252518
TI  - Regulation of inducible nitric oxide synthase and nitric oxide during hepatic
      injury and fibrogenesis.
AB  - Nitric oxide (NO) production via inducible NO synthase (iNOS) is prominent in the
      liver after stimulation with cytokines and/or lipopolysaccharide. The aim of this
      study was to investigate the production of NO via iNOS in specific liver cell
      populations during toxin-mediated and obstructive hepatic injury and
      fibrogenesis. After a single dose of carbon tetrachloride, iNOS mRNA and nitrite
      (a metabolic product of NO) were detected only in Kupffer cells. They were not
      detectable in any cell type after recurrent administration of carbon
      tetrachloride, including in animals with far advanced cirrhosis (i.e., portal
      hypertension and/or ascites). After bile duct ligation, a mechanistically
      different form of liver injury and fibrogenesis, iNOS mRNA and nitrite were
      identified in all nonparenchymal cells but not in hepatocytes. Twenty-four hours
      after bile duct ligation, iNOS mRNA and NO production were greatest in Kupffer
      cells, but after prolonged bile duct ligation, iNOS was found predominantly in
      sinusoidal endothelial cells. These data indicate that iNOS expression varies
      temporally and spatially in the liver after injury and also varies with the type
      of insult.

PMID- 9252521
TI  - Distribution of ICC and motor response characteristics in urinary bladders
      reconstructed from human ileum.
AB  - Motor patterns, intraluminal pressures, volume capacity, and histoanatomic
      characteristics were studied in full thickness specimens from ileal reservoirs
      (orthotopic ileal bladders) removed during corrective surgery. Contractile
      activity was recorded in situ before corrective surgery. Morphological
      examination was performed with both light and electron microscopy. Two
      populations of interstitial cells of Cajal (ICC) were identified: ICC at the
      level of the deep muscular plexus (ICC-DMP) and ICC at the level of the myenteric
      plexus (ICC-MP). The ileal reservoirs left as tubes generated phasic activity
      when filled with liquid, and all retained the ICC-MP; however, after extended
      periods (e.g., 8 yr), these reservoirs lost the ICC-DMP and were less responsive
      to distension. The detubularized ileal reservoirs were not responsive to
      distension and did not generate phasic activity; none had ICC-DMP and all had a
      disrupted ICC-MP network. In conclusion, motor patterns were found to be specific
      for each type of reservoir, and the two populations of ICC had characteristics
      specific for the type of bladder reconstruction.

PMID- 9252520
TI  - Intestinal absorption of undegraded proteins in men: presence of bromelain in
      plasma after oral intake.
AB  - The human adult intestinal epithelium has traditionally been described as
      nonpermeable to proteins. However, indirect evidence suggests that reduced
      absorption of undegraded proteins might take place under physiological
      conditions. Using bromelain (an enzyme obtained from pineapple stems) as a model
      protein, we studied the extent of this mucosal permeation in 19 healthy men. The
      protein was detected in plasma by immunoassay and by its proteolytic activity
      after oral administration. The estimated plasma half-life was 6-9 h. After oral
      multidosing (3 g/day), plasma concentration reached as much as 5,000 pg/ml by 48
      h. From the plasma concentration curve, it could be estimated that an average of
      10.8 micrograms of bromelain was present in plasma in the 3- to 51-h period. The
      presence of undegraded bromelain in plasma was shown unequivocally by
      immunoprecipitation of plasma samples with antibromelain antibodies, followed by
      gel electrophoresis and immunodetection. Moreover, the enzyme retained its
      biological activity, at least in part. Circulating bromelain was found associated
      with alpha 2-macroglobulin and alpha 1-antichymotrypain. The results of this work
      confirm the existence of a small but significant intestinal transport of
      undegraded proteins in healthy men.

PMID- 9252523
TI  - Effect of cholestasis on regulation of cAMP synthesis by glucagon and bile acids
      in isolated hepatocytes.
AB  - Previously, we have reported that bile acids can directly inhibit hormone-induced
      adenosine 3',5'-cyclic monophosphate (cAMP) formation through a protein kinase C
      (PKC)-dependent mechanism [Bouscarel, B., T.W. Gettys, H. Fromm, and H. Dubner.
      Am. J. Physiol. 268 (Gastrointest. Liver Physiol. 31): G300-G310, 1995].
      Therefore, the regulation of cAMP synthesis by glucagon and bile acids was
      investigated in hepatocytes isolated after 2-day ligation of the common bile duct
      in Golden Syrian hamsters. The bile acid concentration was increased 30-fold in
      the serum, whereas it was not significantly different in the bile of duct-ligated
      vs. sham-operated hamsters. The glycine/taurine and cholate/chenodeoxycholate
      ratios were significantly increased fourfold and sevenfold, respectively, only in
      the serum of bile duct-ligated hamsters. Ligation of the bile duct decreased the
      efficacy of glucagon-stimulated cAMP synthesis by 40-50% without changing its
      potency. This attenuation of cAMP synthesis, which was also observed with
      forskolin, remained in the absence of any detectable amount of bile acids in the
      hepatocytes. The decrease in glucagon-stimulated cAMP production was also not
      attributable to changes in either the affinity or the number of receptors for
      this hormone. The potency and efficacy of the bile acids to inhibit glucagon
      induced cAMP formation was also reduced in bile duct-ligated hamsters. The
      inhibitory regulation of cAMP synthesis through angiotensin II was similarly
      diminished after bile duct ligation. Although the total expression of PKC-alpha
      was not affected, an increased translocation by 60% from the cytosol to the
      membrane fraction was observed in hepatocytes isolated after bile duct ligation.
      Therefore, during cholestasis and prolonged exposure of the liver to bile acids,
      both the stimulatory and inhibitory regulatory, mechanisms of cAMP synthesis are
      compromised in an irreversible manner because the effects persist even after
      isolation of the hepatocytes. This decreased regulation of cAMP synthesis is
      possibly mediated through PKC-alpha activation.

PMID- 9252524
TI  - Polyamines are important for attachment of IEC-6 cells to extracellular matrix.
AB  - The inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine
      biosynthesis, with alpha-difluoromethylornithine in IEC-6 cells (small intestinal
      crypt cell line) reduces cell migration by 70%, inhibits protein cross-linking,
      and affects the cytoskeletal assembly. The current study examines the effects of
      intracellular polyamine depletion on attachment of IEC-6 cells to different
      matrices. Polyamine deficiency inhibited cell attachment to plastic, laminin,
      fibronectin, collagen IV, and Matrigel by different extents. Intracellular
      putrescine restored attachment to all matrices. The presence of a specific
      inhibitor of protein cross-linking also inhibited attachment to laminin in a dose
      dependent manner. The inhibition of cell attachment to plastic and Matrigel was
      correlated with the inhibition of cell migration. Immunofluorescence studies
      showed that polyamines are essential for the correct expression of the integrin
      subunit alpha 2 but not for the expression of the alpha 1-subunit. This study
      demonstrates that polyamines are important for cell attachment and expression of
      the integrin alpha 2 beta 1, a putative receptor for collagen and laminin. The
      impairment of protein cross-linking and the inhibition of the expression of cell
      surface receptors that bind extracellular matrix (ECM) proteins may be part of
      the mechanism by which polyamine deficiency retards cell migration in the small
      intestine.

PMID- 9252522
TI  - Exposure to cigarette smoke delays the plasma clearance of chylomicrons and
      chylomicron remnants in rats.
AB  - We investigated the effects of cigarette smoke exposure on the clearance of
      chylomicrons (CM) and CM remnants in rats after administration of a fat
      containing meal. There was a decrease in clearance of both postprandial CM and
      exogenous radiolabeled CM in smoke-exposed animals. For exogenous CM, clearance
      (t1/2) increased significantly for both triglyceride and cholesterol labels and
      correlated with the delay in liver uptake. This decrease in lipid clearance could
      not be explained by decreased lipoprotein lipase (LPL) activity because smoke
      exposure resulted in a significant increase in LPL activity. When the hydrolysis
      of CM by endothelial LPL was tested in a heart perfusion system, there was no
      difference in CM hydrolysis between the two groups. Hepatic lipase activity was
      also unchanged in smoke-exposed animals. However, there was a significant delay
      in the CM remnant uptake into livers isolated from smoke-exposed rats. Thus the
      delay in CM clearance in smoke-exposed animals cannot be attributed to reduced
      lipase activities but results from impaired hepatic uptake of CM remnants.

PMID- 9252525
TI  - Rapid in vivo hydrolysis of fatty acid ethyl esters, toxic nonoxidative ethanol
      metabolites.
AB  - Fatty acid ethyl esters (FAEE), esterification products of fatty acids and
      ethanol, are in use as fatty acid supplements, but they also have been implicated
      as toxic mediators of ethanol ingestion. We hypothesized that hydrolysis of
      orally ingested FAEE occurs in the gastrointestinal (GI) tract and in the blood
      to explain their apparent lack of toxicity. To study the in vivo inactivation of
      FAEE by hydrolysis to free fatty acids and ethanol, we assessed the hydrolysis of
      FAEE administered as an oil directly into the rat stomach and when injected
      within the core of low-density lipoprotein particles into the circulation of
      rats. Our studies demonstrate that FAEE are rapidly degraded to free fatty acids
      and ethanol in the GI tract at the level of the duodenum with limited hydrolysis
      in the stomach. In addition, FAEE are rapidly degraded in the circulation, with a
      half-life of only 58 s. Thus the degradation of FAEE in the GI tract and in the
      blood provides an explanation for the apparent lack of toxicity of orally
      ingested FAEE.

PMID- 9252526
TI  - Calcitonin gene-related peptide in viscerosensitive response to colorectal
      distension in rats.
AB  - The role of calcitonin gene-related peptide (CGRP) on colorectal distension
      induced visceral pain was investigated in conscious rats. Intracolonic
      administration of acetic acid (0.6%) resulted in a significantly increased number
      of abdominal contractions in response to colorectal balloon distension from 5.8
      +/- 1.2 in controls to 16.6 +/- 1.0 in acetic acid-treated animals (P < 0.05),
      evidencing sensitization of visceral afferent pathways and subsequently visceral
      hyperalgesia. This sensitization phenomenon was not observed in animals
      previously treated with systemic capsaicin. Likewise, in animals not treated with
      capsaicin, use of an intravenous antagonist for CGRP [human CGRP-(8-37)],
      completely reversed the sensitizing effects of acetic acid. Furthermore,
      intravenous administration of CGRP dose dependently increased the number of
      abdominal contractions in response to colorectal distension from 3.0 +/- 1.1
      (CGRP 250 ng) to 17.0 +/- 1.2 (CGRP 500 ng, P < 0.05), as previously observed in
      acetic acid-treated animals. Finally, intrathecal administration of hCGRP-(8-37)
      (mid-lumbar) also resulted in a total dose-dependent reversal of CGRP (500 ng) or
      acetic acid-induced visceral hypersensitivity. These results demonstrate that
      CGRP plays a major role in this model of visceral afferent nerve sensitization
      from gastrointestinal origin.

PMID- 9252527
TI  - Glucocorticoids upregulate taurocholate transport by ileal brush-border membrane.
AB  - The regulation of the enterohepatic circulation of bile acids has not been fully
      elucidated. Substrate availability has been shown to have a regulatory role on
      the ileal uptake of taurocholate (TC) by a positive feedback mechanism. Other
      mechanisms are likely to be involved in regulating ileal bile acid uptake. The
      present study was designed to test the hypothesis that the ileal bile acid
      transporter (iBAT) is glucocorticoid sensitive and that changes in expression are
      mediated by changes in iBAT synthesis. Adult Sprague-Dawley rats (300-400 g)
      received intraperitoneal injections with either corticosterone (5 mg/ 100 g body
      weight) or an equivalent vehicle (control) daily for 3 days. On day 4, ileal
      brush-border membrane vesicles (BBMV) and hepatic basolateral membrane vesicles
      (BLMV) were prepared, and TC transport was performed using the rapid filtration
      technique. Initial velocity was measured at selected time points, and kinetics
      were calculated over a range of TC concentrations. Ileal RNA was isolated, and
      Northern analysis of steady-state iBAT mRNA levels was determined. Western blot
      analysis was performed to quantitate the level of the 48-kDa iBAT protein. The
      initial velocity of Na(+)-dependent TC uptake at 30 s by ileal BBMV was higher in
      treated animals (264.3 +/- 64.6 pmol/mg protein) compared with control animals
      (148.3 +/- 41.1 pmol/mg protein; P = 0.07). The maximal velocity of uptake (Vmax)
      was significantly higher in treated vs. control animals (1,091 +/- 62.7 vs. 689.1
      +/- 55.0 pmol.min-1.mg protein-1, respectively; P = 0.002), whereas there was no
      significant difference in the Michaelis constant (Km) between the control and
      treated animals (43.3 +/- 7.2 vs. 35.3 +/- 8.7 microM, respectively; P = not
      significant). Steady-state iBAT mRNA levels were increased twofold in the treated
      vs. control groups. Western blot analysis showed that the abundance of the 48-kDa
      iBAT protein was eightfold higher in the treated animals compared with control.
      Kinetic analysis of hepatic Na(+)-dependent TC uptake revealed nearly identical
      Vmax and Km between the study and control animals. Therefore, we conclude that TC
      transport by ileal BBMV is upregulated by administration of glucocorticoids. The
      increase in BBMV transport Vmax corresponds to an increase in both iBAT
      transcript and protein.

PMID- 9252528
TI  - Bovine pancreatic duct cells express cAMP- and Ca(2+)-activated apical membrane
      Cl- conductances.
AB  - Secretion of salt and water by the epithelial cells that line pancreatic ducts
      depends on activation of apical membrane Cl- conductance. In the present study,
      we characterized two types of Cl- conductances present in the apical cell
      membrane of bovine pancreatic duct epithelial cells. Primary cultures of bovine
      main pancreatic duct epithelium and an immortalized cell line (BPD1) derived from
      primary cultures were used. Elevation of intracellular adenosine 3',5'-cyclic
      monophosphate (cAMP) or Ca2+ in intact monolayers of duct epithelium induced
      sustained anion secretion. Agonist-induced changes in plasma membrane Cl-
      permeability were accessed by 36 Cl- efflux, whole cell current recording, and
      measurements of transepithelial Cl- current across permeabilized epithelial
      monolayers. Elevation of intracellular cAMP elicited a sustained increase in Cl-
      permeability, whereas elevation of intracellular Ca2+ induced only a transient
      increase in Cl- permeability. Ca(2+)- but not cAMP-induced increases in Cl-
      permeability were abolished by preincubation of cells with the Ca2+ buffer 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl) ester
      (BAPTA-AM). N-phenylanthranilic acid (DPC; 1 mM) and glibenclamide (100 microM),
      but not 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; 500 microM),
      inhibited the cAMP-induced increase in Cl- permeability. In contrast, DPC and
      DIDS, but not glibenclamide, inhibited the Ca(2+)-induced increase in Cl-
      permeability. We conclude from these experiments that bovine pancreatic duct
      epithelial cells express at least two types of Cl- channels, cAMP and Ca2+
      activated, in the apical cell membrane. Because the Ca(2+)-activated increase in
      Cl- permeability is transient, the extent to which this pathway contributes to
      sustained anion secretion by the ductal epithelium remains to be determined.

PMID- 9252529
TI  - Expression of insulin receptors and of 60-kDa receptor substrate in rat mature
      and immature enterocytes.
AB  - The mechanism(s) by which rat immature enterocytes exhibit increased
      responsiveness to insulin before weaning is unknown. Therefore, we have analyzed
      the distribution, ontogeny, and molecular properties of insulin receptors (IR)
      and of related substrates in immature and mature enterocytes. IR were studied by
      radioligand binding assays, cross-linking labeling, immunohistochemistry, and in
      vitro phosphorylated substrates by immunoprecipitation. Regardless of age, 125I
      insulin binding to IR was five times higher in crypt cells than in villus cells
      and two times higher in the ileum than in the jejunum. Binding capacity to villus
      cells from sucklings (day 14) exceeded three times that of older animals (day 30
      and day 60). Scatchard analysis of equilibrium binding data confirmed an age
      related decrease in low- and high-affinity receptor classes without change in
      affinity constants. In concordance, both alpha- and beta-IR subunits were more
      abundant in immature than in mature membranes. In vitro, insulin elicited the
      phosphorylation of three membrane proteins (96, 60 and 42 kDa), whose signals
      were virtually inhibited by preincubating membranes with antireceptor monoclonal
      antibodies. By immunoprecipitation, the 60-kDa signal was rapidly detected as a
      tyrosine-phosphorylated protein, expressed in mature and immature membranes, and
      identified as a receptor substrate phosphorylated in vitro by the IR tyrosine
      kinase. In conclusion, 1) increased responsiveness of rat immature enterocytes to
      insulin could be related to high membrane concentrations of IR and 2) normal rat
      enterocytes express a 60-kDa phosphotyrosine protein identified as a direct
      substrate of the IR tyrosine kinase.

PMID- 9252530
TI  - Nontraditional effects of protein binding and hematocrit on uptake of indocyanine
      green by perfused rat liver.
AB  - We used a novel parameter-free approach to study the role of protein binding in
      the hepatic clearance of indocyanine green (ICG) from reconstituted pig blood by
      perfused rat liver. Either perfusate total plasma protein concentration or
      hematocrit was changed. By analyzing protein concentration ratios or plasma
      volume ratios relative to ratios of intrinsic hepatic clearance of ICG (K), it
      was possible to evaluate current models of hepatic uptake of protein-bound
      ligands without precise knowledge of some of the model parameters. A four-fold
      increase in the total plasma protein concentration produced only a 36% decrease
      in K. This was substantially less than predicted by the traditional model, where
      K is proportional to the free concentration of ligand. Because an unstirred water
      layer effect could not by itself account for the observations, the effects of
      binding disequilibrium in the sinusoids or uptake directly from the bound pool
      had to be considered. To discriminate, hematocrit was increased from 15% to 29%,
      causing a 20% decrease in the sinusoidal plasma volume. A significant reduction
      in K strongly suggested a sinusoidal binding disequilibrium effect. The
      dissociation rate constant predicted by this model was confirmed by in vitro
      measurement, further supporting this interpretation. The simple experimental
      design and its parameter-free evaluation provide a new tool for investigating the
      hepatic uptake of protein-bound ligands.

PMID- 9252531
TI  - Models for the regulation of purine metabolism in rat hepatocytes: evaluation of
      tracer kinetic experiments.
AB  - Metabolic pathways are characterized by numerous regulatory mechanisms. Their
      study calls for the determination of the metabolite concentrations as well as the
      flux rates. Corresponding experiments using purified enzymes and an artificial
      environment frequently yield results that differ from findings for in vivo
      systems. To be more realistic, the tracer kinetic experiments presented here
      involved intact isolated hepatocytes. It is necessary to establish mathematical
      models to deduce the flux rates. With the presumption of metabolic steady-state
      conditions, the flux rates are determined by a possibly stiff system of linear
      differential equations. For the first time, the flux rate determination in the
      purine metabolism of rat hepatocytes was accomplished by applying a combination
      of a nonlinear least-square fit and a numerical integration. Because of the
      complexity of this pathway, it was necessary to use three different tracers
      requiring three partial models. By ensuring their compatibility and using a fit
      of high statistical quality, the experimental situation could be described
      adequately. Our flux rate analysis confirmed earlier experimental findings and
      also allows much more insight into the regulatory mechanisms of the metabolism
      studied.

PMID- 9252532
TI  - Tyrosine phosphorylation in contraction of opossum esophageal longitudinal muscle
      in response to SNP.
AB  - Sodium nitroprusside (SNP) has been shown to elicit a guanosine 3',5'-cyclic
      monophosphate (cGMP)-mediated, indomethacin-sensitive contraction of the opossum
      esophageal longitudinal muscle. We examined the role of tyrosine phosphorylation
      in the signal transduction pathway of contractions induced by SNP and cGMP in
      longitudinal muscle strips in vitro. Force of isometric contractions was
      expressed as the percentage of responses to KCl (73 mM). SNP (100 microM)-induced
      contractions were 75 +/- 5% before and 3 +/- 2% after 50 microM genistein (P <
      0.005) and 86 +/- 16% before and 0 +/- 0% after 50 microM tyrphostin B46.
      Contractions in response to 8-bromo-cGMP (8-BrcGMP; 1 mM) were 74 +/- 15% before
      and 3 +/- 2% after genistein (P < 0.01) and 63 +/- 15% before and 18 +/- 4% after
      tyrphostin B46 (P < 0.05). In contrast, KCl-induced contractions were 82 +/- 8%
      and 96 +/- 9% of the control value after genistein and tyrphostin B46 treatments,
      respectively (P > 0.05 for both). Carbachol contractions were partially
      suppressed by genistein (106 +/- 8% vs. 79 +/- 8%; P < 0.05) but unaffected by
      tyrphostin B46 (114 +/- 10% vs. 107 +/- 12%; P > 0.05). Western blot analysis
      revealed a 116-kDa phosphotyrosine protein in the control muscle strips. The
      level of this protein was increased to 206 +/- 15% of control after SNP
      treatment. Both genistein and tyrphostin B46 blocked this increase. These studies
      show that contractions of the esophageal longitudinal muscle induced by SNP and
      cGMP utilize a signal transduction pathway different from that used by the
      depolarizing agent KCl and the muscarinic agonist carbachol. Contractions induced
      by SNP and cGMP involve tyrosine phosphorylation of a protein, possibly
      identified as a 116-kDa protein, as a key step in the signaling pathway.

PMID- 9252533
TI  - The stress response and the lung.
AB  - The stress response is a highly conserved cellular defense mechanism defined by
      the rapid and specific expression of stress proteins, with concomitant transient
      inhibition of nonstress protein gene expression. The stress proteins mediate
      cellular and tissue protection against diverse cytotoxic stimuli. Among the many
      classes of stress proteins, heat shock protein 70 and heme oxygenase-1 are the
      best characterized with respect to lung biology. A potential role for stress
      proteins in human lung disease is inferred from studies demonstrating stress
      protein expression in the lungs of patients with cancer, asthma, and acute lung
      injury. Several examples of stress protein-mediated cytoprotection exist in cell
      and animal models of acute lung injury. Stress protein induction protects rats
      against acute lung injury caused by either systemic administration of endotoxin
      or intratracheal administration of phospholipase A1. In vitro, increased
      expression of stress proteins protects lung cells against endotoxin-mediated
      apoptosis and oxidant injury. The mechanisms of stress response-mediated
      cytoprotection may involve the enzymatic and molecular chaperone properties of
      stress proteins. Alternatively, the stress response may protect by modulating
      lung proinflammatory responses. Data from extrapulmonary systems suggest that
      stress response-associated factors (heat shock protein 70 and heat shock factor)
      are directly involved in modulation of proinflammatory gene expression. Recent
      evidence also demonstrates interactions between the stress response and the I
      kappa B/nuclear factor-kappa B pathway in cultured lung cells. Increased
      understanding about the role of stress proteins in lung biology may support
      efforts to selectively increase expression of one or more stress proteins to
      provide protection against human acute lung injury.

PMID- 9252534
TI  - Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle
      cells.
AB  - Enhanced proliferation of airway smooth muscle is thought to contribute to the
      pathogenesis of asthma and other obstructive airway diseases. Lysophosphatidic
      acid (LPA) is a simple bioactive lipid mediator that stimulates mitogenesis in
      fibroblasts and some other cell types. The effects of LPA on mitogenesis of
      cultured human airway smooth muscle cells were determined by measuring
      [3H]thymidine incorporation into cellular DNA. LPA induced a concentration
      dependent stimulation of [3H]thymidine incorporation of a similar magnitude to
      that induced by serum, with the effects of 50 microM LPA being similar to those
      of 5% serum. Stimulation by LPA and by serum was almost completely eliminated in
      cells exposed to pertussis toxin, indicating involvement of a pertussis toxin
      sensitive G protein in mitogenic signaling by these agents. Epidermal growth
      factor (EGF) induced stimulation of a similar magnitude as that with LPA, but the
      stimulation by EGF was insensitive to pertussis toxin. LPA and EGF, when added
      together, exhibited a markedly synergistic stimulation of [3H]thymidine
      incorporation that was typically 10-fold greater than the stimulation with either
      agent alone. LPA and EGF also stimulated mitogenesis assessed by cell growth, and
      again LPA and EGF together exhibited synergism. These results suggest the
      possibility that stimulation of airway smooth muscle cell proliferation by LPA,
      either alone or by enhancing effects of other growth factors, could play a role
      in normal airway remodeling or in the pathological proliferation of smooth muscle
      in various airway diseases.

PMID- 9252536
TI  - Ca(2+)-inhibitable adenylyl cyclase and pulmonary microvascular permeability.
AB  - Intracellular mechanisms responsible for endothelial cell disruption are unknown,
      although either elevated cytosolic Ca2+ ([Ca2+]i) or decreased adenosine 3',5'
      cyclic monophosphate (cAMP) promotes permeability. Recent identification that
      Ca(2+)-inhibitable adenylyl cyclase establishes an inverse relationship between
      [Ca2+]i and cAMP in macrovascular endothelial cells provided a possible mechanism
      of development of permeability. However, these data utilized an in vitro model;
      lacking was evidence supporting 1) expression of Ca(2+)-inhibitable adenylyl
      cyclase in pulmonary microvascular endothelium and 2) Ca2+ inhibition of adenylyl
      cyclase and cAMP content as a paradigm for inflammatory mediator-induced
      permeability in the intact circulation. We therefore addressed these issues in
      microvascular endothelial cells derived from rat lung and in an isolated perfused
      rat lung preparation. Results demonstrate expression of a Ca(2+)-inhibitable
      adenylyl cyclase in microvascular endothelial cells. Furthermore, data suggest
      that Ca2+ inhibition of adenylyl cyclase is necessary for development of
      microvascular permeability in the intact circulation. We conclude Ca2+ inhibition
      of cAMP represents a critical step in genesis of microvascular permeability in
      the intact pulmonary circulation.

PMID- 9252535
TI  - Association of granular exocytosis with Ca(2+)-activated K+ channels in human
      eosinophils.
AB  - We studied the mechanism of degranulation caused by Ca(2+)-activated K+ channels
      (KCa channels) in eosinophils isolated from mildly atopic donors using negative
      immunoselection. Stimulation of eosinophils with 0.1 microM platelet-activating
      factor (PAF) caused activation of single channels as recorded by the cell
      attached patch-clamp technique. These channels were selectively permeable to K+
      because the reversal potential was close to the equilibrium potential for K+.
      However, the channels were not permeable to Na+ or Cl- as demonstrated by ion
      substitution experiments. The calcium ionophore A-23187, at 1 microM, increased
      the K+ channel activity in the presence of Ca2+ in the external perfusate but did
      not induce channel activity in the absence of Ca2+. Similar results were obtained
      with another calcium ionophore, ionomycin (1 microM), and the Ca(2+)-releasing
      agent thapsigargin (10 microM). K+ channels activated by PAF and A-23187 had
      similar characteristics: two levels of single-channel conductances were observed,
      10 +/- 1.5 and 22 +/- 1.7 pS as induced by PAF and 11 +/- 1.3 and 24 +/- 1.9 pS
      by A-23187; the mean open times of the large-conductance channels were 1.45 +/-
      0.3 ms as induced by PAF and 1.26 +/- 0.5 ms by A-23187. These results indicate
      that PAF activates KCa channels. Both KCa currents and major basic protein
      release caused by A-23187 were blocked by quinidine. It is suggested that KCa
      channels are associated with granule secretion in human eosinophils.

PMID- 9252537
TI  - SEB is cytotoxic and alters EC barrier function through protein tyrosine
      phosphorylation in vitro.
AB  - We studied whether Staphylococcal enterotoxin B (SEB) has direct effects on
      endothelial cells (EC) in the absence of effector cells or their products. Bovine
      or human pulmonary artery EC were grown to confluence on filters mounted in
      chemotaxis chambers. Barrier function was assessed by placing [14C]bovine serum
      albumin in the chamber and sampling the lower well for 14C activity. SEB
      exposures induced a significant (P < 0.001) dose- and time-dependent increase in
      albumin flux across both bovine and human EC monolayers. Albumin flux was
      temperature dependent, and cycloheximide pretreatment of the monolayers did not
      block the SEB-induced increase in permeability. Preincubation of SEB with trypsin
      or anti-SEB antibody significantly (P < 0.0001) reduced the effect, whereas
      pretreatment with polymyxin B did not. SEB at > or = 10 micrograms/ml
      significantly (P < 0.03) increased EC injury as measured by 51Cr release in a
      dose- and time-dependent manner. Herbimycin and genistein, inhibitors of protein
      tyrosine kinases, each protected against SEB-induced cytotoxicity, barrier
      dysfunction, and intercellular gap formation. We conclude that SEB perturbs
      endothelial barrier function and viability in the absence of effector cells or
      their mediators.

PMID- 9252538
TI  - Effect of hyperoxia on substance P expression and airway reactivity in the
      developing lung.
AB  - This study was undertaken to characterize changes in the tachykinin system
      induced by hyperoxic exposure and the potential effects on airway contractile
      responses. We exposed 7-day-old rat pups to either room air or hyperoxia (> 95%
      O2) for 7 days to assess pulmonary beta-preprotachykinin (beta-PPT) gene
      expression, substance P (SP) levels, and airway contractile responses to
      cholinergic stimulation before and after neurokinin-1 (NK1) receptor blockade.
      Lung beta-PPT mRNA expression, lung and tracheal SP levels, and contractile
      responses to exogenous acetylcholine and electrical field stimulation were
      measured in vitro in normoxia- and hyperoxia-exposed tracheal cylinders.
      Hyperoxia caused a 1.1- to 2.6-fold increase in steady-state lung beta-PPT mRNA
      and a 50 and 32% increase in SP levels of lung and trachea, respectively. In
      response to cholinergic stimulation, maximal contractile force (Emax) of
      hyperoxia exposed tracheal muscle was significantly higher than for normoxic
      controls. Addition of the SP (NK1) receptor blocker CP-99994 (10 microM)
      decreased sensitivity to electrical field stimulation in both hyperoxic and
      normoxic trachea without a significant decline in Emax. These data provide
      evidence for both increased SP production and enhanced maximal contractile
      responses of hyperoxia-exposed neonatal trachea to cholinergic stimulation. The
      tachykinin peptide SP does not, however, appear to play a major role in the
      enhanced airway reactivity associated with hyperoxic lung injury during early
      postnatal life.

PMID- 9252539
TI  - Ischemia-reperfusion lung injury: contribution of ischemia, neutrophils, and
      hydrostatic pressure.
AB  - We used an isolated, blood-perfused rat lung model to evaluate the separate roles
      of ischemia and reperfusion time, the changes in pulmonary artery pressure (Ppa),
      and the circulating neutrophil number in mediating ischemia-reperfusion lung
      injury. Extravascular albumin accumulation was used to quantify changes in the
      permeability of the alveolar capillary membranes. In animals subjected to 30 and
      45 min of ischemia without reperfusion, extravascular albumin accumulation was
      significantly higher than in controls subjected to continuous perfusion (P <
      0.05). Albumin accumulation in animals subjected to 45 min of ischemia was
      greater compared with those undergoing 30 min of ischemia followed by 30 min of
      reperfusion (P < 0.05). In animals undergoing 45 min of ischemia followed by 30
      min of reperfusion, a linear relationship was demonstrated between changes in Ppa
      and extravascular albumin accumulation. Reducing Ppa with a thromboxane
      antagonist (ICI-192605) and a smooth muscle relaxant (papaverine) produced, in
      both cases, a significant decrease in albumin extravasation (P < 0.05). No
      significant difference in extravascular albumin accumulation or change in Ppa was
      shown in neutrophil-depleted animals compared with nondepleted animals. We
      conclude that ischemia time contributes significantly to ischemia-reperfusion
      lung injury and that transient changes in Ppa after reperfusion exacerbate and
      injury in this model. This early injury demonstrated here was neutrophil
      dependent.

PMID- 9252540
TI  - Clearance of intra-amniotic lung surfactant: uptake and utilization by the fetal
      rabbit lung.
AB  - To investigate the metabolism of intra-amniotic surfactant, surfactant containing
      double-labeled dipalmitoylphosphatidylcholine (DPPC) was injected in amniotic
      fluid on days 23-27 of gestation. Within 44 h, DPPC was distributed to the
      gastrointestinal tract (45.9%), fetal membranes and placenta (8.2%), fetal lung
      (6.6%), and liver (1.9%). DPPC uptake was higher in the upper than in the lower
      lung lobes. The mixture of phosphatidylglycerol and DPPC increased the uptake of
      DPPC that was not saturable (range 15-60 mg phospholipid). There was no
      detectable metabolism of DPPC taken up by the fetal lung. Surfactant protein A,
      originating from intra-amniotic heterplogous surfactant, was detected
      immunohistochemically in alveolar epithelium. Intra-amniotic surfactants did not
      affect the expression of surfactant protein mRNAs. Intra-amniotic surfactant
      (1,500-2,000 mg/kg on day 25.3) improved lung compliance of ventilated 27.0-day
      premature rabbits less than intratracheal surfactant at birth (75-100 mg/kg).
      Reutilization by the alveolar epithelium of surfactant secreted to future
      airspaces, airways, and amniotic fluid may be a mechanism that increases
      intracellular surfactant pool before birth.

PMID- 9252541
TI  - Fas expression in pulmonary alveolar type II cells.
AB  - Fas, a type I membrane receptor protein, transduces a signal culminating in
      apoptosis after binding to the Fas ligand. Information regarding the expression
      of Fas in nonlymphoid tissues, although limited, suggests a role for Fas in
      epithelial progenitor cell populations. In this paper, we provide several lines
      of evidence indicating that the progenitor cell of the alveolus, the type II
      cell, displays restricted expression of Fas. We found 1) Fas gene expression in
      RNA derived from fresh isolates of primary rat type II cells; 2) restriction of
      Fas expression to a subset of alveolar type II cells by in situ hybridization and
      immunohistochemistry of the normal mouse lung; 3) induction of apoptosis in a
      mouse lung type II epithelial cell line (MLE) after activation of Fas; and 4)
      induction of apoptosis in a subpopulation of type II cells after the
      intratracheal instillation of an activating anti-Fas antibody in mice. These
      findings suggest that Fas-dependent apoptosis is involved in regulating turnover
      of the alveolar epithelium.

PMID- 9252542
TI  - Endothelin receptor changes in hypoxia-induced pulmonary hypertension in the
      newborn piglet.
AB  - Endothelin (ET)-1, a potent vasoconstrictor and mitogen, acts through ETA and ETB
      receptors and may be involved in the pathogenesis of persistent pulmonary
      hypertension of the newborn. We hypothesized that hypoxia-induced pulmonary
      hypertension in the newborn is associated with increased ET-1 release and
      modified ET receptor characteristics leading to vasoconstriction and vascular
      remodeling. Therefore, we studied 1-day-old piglets exposed for 3 or 14 days to
      hypoxia (fraction of inspired O2 = 0.10) or normoxia (controls). ET-1 circulating
      levels in pulmonary artery and vein were measured. Pulmonary vascular reactivity
      to ET-1 was evaluated using isolated-perfused lungs. ET binding characteristics
      were examined in microsomes from pulmonary arteries (down to 100 microns). ET-1
      circulating levels are low and are not altered by hypoxia. The magnitude of the
      initial dilator response to ET-1 decreases after 3 days of hypoxia (P < 0.05),
      whereas the number of ETB receptors is reduced by 40% in the pulmonary arteries
      (P < 0.05). ETA receptors are predominant (65-90%) in pulmonary arteries. ETA
      receptors decrease by 50% after 14 days of exposure to hypoxia (P < 0.05),
      whereas the constrictor response to ET-1 remains unchanged. The fact that the
      reduction in vasodilator response parallels the decrease in ETB receptors
      suggests a decrease in receptor expression. We speculate that the maintenance of
      the vasoconstrictor response to ET-1 despite a reduction in the number of binding
      sites is likely due to receptor occupancy. In conclusion, in the newborn piglet
      pulmonary vasculature, ETA and ETB receptors may be affected differently by
      hypoxia.

PMID- 9252543
TI  - Halothane inhibits agonist-induced potentiation of rMLC phosphorylation in
      permeabilized airway smooth muscle.
AB  - Agonist-induced increases in CA2+ sensitivity are mediated in part by mechanisms
      that increase phosphorylation of the regulatory myosin light chain (rMLC) at
      constant cytosolic Ca2+ concentration ([Ca2+]i). The current study tested the
      hypothesis that halothane inhibits acetylcholine (ACh)-induced potentiation of
      rMLC phosphorylation in beta-escin-permeabilized canine tracheal smooth muscle.
      ACh plus GTP significantly potentiated the increase in isometric force and rMLC
      phosphorylation induced by 0.8 microM free Ca2+. However, whereas the
      potentiation of isometric force was sustained, the potentiation of rMLC
      phosphorylation was biphasic, peaking at 0.5 min and then declining by
      approximately 10 min to a steady-state level significantly above that induced by
      0.8 microM free Ca2+ alone. This finding suggests that mechanisms in addition to
      changes in rMLC phosphorylation may mediate ACh-induced Ca2+ sensitization, as
      has been reported for vascular smooth muscle. Halothane (0.91 +/- 0.10 mM)
      significantly inhibited ACh plus GTP-induced potentiation of rMLC phosphorylation
      and isometric force after 2 (peak rMLC phosphorylation) and 15 (steady-state rMLC
      phosphorylation) min of stimulation. However, the effect of halothane on the
      potentiation of isometric force was significantly less than that expected from
      its effect on rMLC phosphorylation (i.e., halothane changed the relationship
      between rMLC phosphorylation and isometric force). These results demonstrate that
      halothane inhibits the ACh-induced increase in Ca2+ sensitivity by inhibiting the
      membrane receptor-coupled mechanisms that increase rMLC phosphorylation at
      constant submaximal [Ca2+]i. Possible additional effects of halothane on rMLC
      phosphorylation-independent mechanisms cannot be ruled out.

PMID- 9252544
TI  - Adrenal hormone regulation of fibronectin synthesis by type II pulmonary
      epithelial cells.
AB  - Previous work suggested an association between changes in the alveolar
      extracellular matrix and epithelial cell growth in lungs of adrenalectomized rats
      in vivo. Other studies demonstrated that adrenal hormones modulate extracellular
      matrix synthesis by type II pulmonary epithelial cells in vitro. Adrenal hormone
      regulation of type II cell fibronectin synthesis was thus examined. Fibronectin
      synthesis was quantitated by immunoprecipitation of the metabolically labeled
      molecule from cells, extracellular matrix, and culture medium. On day 1 of
      primary culture, synthesis of matrix fibronectin by type II cells isolated from
      the lungs of adrenalectomized animals was more than twice that by cells isolated
      from control rats. Adrenalectomy elevated steady-state fibronectin mRNA levels in
      primary isolates of type II cells cultured for 1 or 3 days. These results suggest
      that altered fibronectin synthesis and deposition into the extracellular matrix
      accompany changes in type II cell phenotype that occur after adrenalectomy.

PMID- 9252545
TI  - Localization of eosinophils to airway nerves and effect on neuronal M2 muscarinic
      receptor function.
AB  - Neuronal M2 muscarinic receptors inhibit acetylcholine release from pulmonary
      parasympathetic nerves but are dysfunctional in antigen-challenged animals and
      asthmatics. Deletion of pulmonary eosinophils protects M2 receptor function in
      antigen-challenged guinea pigs. Therefore, the association of eosinophils with
      airway nerves was investigated. Nerve-associated eosinophils were significantly
      increased in challenged animals compared with controls (0.75 +/- 0.05 vs. 0.28 +/
      0.05 eosinophils/nerve). In antigen-challenged animals, eosinophil density was
      greatest around airway nerves, suggesting recruitment to the nerves. M2 receptor
      function was inversely correlated with the number of eosinophils per nerve, thus
      eosinophils are associated with airway nerves in antigen-challenged guinea pigs,
      where they impair M2 receptor function. In airways from three patients with fatal
      asthma, 196 of 637 eosinophils (30%) were associated with nerves, and release of
      eosinophil major basic protein was evident; conversely, in three control patients
      1 of 11 (9%) eosinophils were in contact with nerves. Thus eosinophils and their
      granule proteins are also seen in association with airway nerves in patients with
      asthma.

PMID- 9252546
TI  - Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury
      in rats.
AB  - Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the
      pathogenesis of adult respiratory distress syndrome. Because the alveolar
      epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic
      effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar
      PMN function in two rat models of acute lung injury induced by alveolar
      instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas
      aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4
      and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial
      partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical
      ventilation. The severity of lung injury in the two models was clearly different,
      since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries,
      respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen
      metabolite production, and proteinase (elastase, gelatinase B) secretions of ex
      vivo alveolar PMNs were not larger in the PYO model. Thus the difference in
      severity was not associated with variations in alveolar neutrophil recruitment or
      activation. Moreover, gelatinase and leukocyte elastase activities were absent in
      bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar
      spaces. We conclude that alveolar neutrophils are not sufficient to create severe
      respiratory failure.

PMID- 9252547
TI  - Peripheral hypertension and alterations in pulmonary vascular regulation.
AB  - We have recently reported in normal isolated-perfused rat lungs that low basal
      tone appears to be regulated by nitric oxide (NO)-dependent and -independent
      mechanisms of soluble guanylate cyclase activation. In this study, we examined
      the role of NO in the regulation of pulmonary artery (PA) tone from rats with
      renin-dependent hypertension. Rats were made hypertensive by ligating the
      abdominal aorta above the left and below the right renal artery (aortic
      coarctation, AC). Mean arterial pressure significantly increased from 119 +/- 8.4
      mmHg in control animals to 156 +/- 15 mmHg 7-14 days after AC surgery. PA
      pressures, however, remained unchanged (8.5 +/- 3.4 mmHg in control animals vs.
      11 +/- 3.3 mmHg in AC animals). Hypoxic contractions in U-46619 precontracted
      isolated small PA (160-260 microns diameter) were significantly increased from 51
      +/- 13 mg in the control group to 142 +/- 38 mg (P < or = 0.05) in AC animals.
      Nitro-L-arginine (NLA; 100 microM) contractions were also enhanced in the AC
      animal. The enhanced NLA response may correlate with an increase in endothelial
      cell NO synthase (NOS) as detected by Western blotting (132 +/- 28% of control; P
      < 0.05). These data suggest that, in this renin-dependent model of systemic
      hypertension, there is increased endothelial cell NOS activity that maintains low
      PA tone, preventing the lung from developing increased pressures.

PMID- 9252548
TI  - Estrogen acutely stimulates nitric oxide synthase activity in fetal pulmonary
      artery endothelium.
AB  - Estrogen (E) has nitric oxide (NO)-mediated effects in certain vascular beds, and
      fetal E levels rise acutely with parturition, suggesting that E may be involved
      in NO-mediated pulmonary vasodilation at birth. We tested the hypothesis that E
      acutely stimulates NO synthase (NOS) activity in ovine fetal pulmonary artery
      endothelial cells (PAEC) by measuring L-[3H]arginine conversion to L
      [3H]citrulline in intact cells. NOS activity in the presence of 17 beta-estradiol
      (E2 beta) rose in a dose-dependent manner, increasing 70-100%, with a threshold
      concentration of 10(-10) M. This effect was detectable within 5 min of E2 beta
      exposure, and the maximal response was comparable to that obtained with
      acetylcholine, which had a threshold concentration of 10(-8) M. Ca2+ removal
      completely inhibited E2 beta-stimulated NOS activity, and activity with E2 beta
      and the Ca2+ ionophore A-23187 was not additive. In addition, the expression of
      the endothelial isoform of NOS (eNOS) was not altered, and the inducible and
      neuronal NOS isoforms were not detected by immunoblot analysis. These findings
      indicate that E2 beta acutely stimulates eNOS by Ca2+ influx. Furthermore, E2
      beta-stimulated NOS activity was fully inhibited by the E receptor (ER)
      antagonists tamoxifen and ICI-182,780, and ER mRNA expression was evident in
      reverse transcription-polymerase chain reaction assays. Thus E acutely stimulates
      eNOS activity in fetal PAEC via the activation of endothelial ER and increases in
      intracellular Ca2+.

PMID- 9252549
TI  - CFTR activation: additive effects of stimulatory and inhibitory phosphorylation
      sites in the R domain.
AB  - To investigate the functional significance of individual consensus
      phosphorylation sites within the R domain of cystic fibrosis transmembrane
      conductance regulator (CFTR), serines were eliminated by substituting them with
      alanine. Included in this analysis were serine-660, -670, -686, -700, -712, -737,
      -768, -795, and -813, which lie within protein kinase A consensus sequences, and
      serine-641, which does not. Elimination of single potential phosphorylation sites
      altered the sensitivity of CFTR (expressed in Xenopus oocytes) to activating
      conditions in a manner that was highly site dependent. Substitution at serine
      660, -670, -700, -795, or -813 significantly increased the half-maximal
      activation constant (KA) for activation by 3-isobutyl-1-methylxanthine, which is
      consistent with the hypothesis that phosphorylation at any of these sites
      promotes CFTR activation. The effect of substitution at serine-813 was
      significantly greater than at the other sites. In contrast, alanine substitution
      at serine-737 or -768 actually decreased the KA for activation, suggesting that
      phosphorylation at either of these sites is inhibitory. Substitution at serine
      641, -686, and -712 had no significant effect on activation sensitivity. The
      effects of multiple serine to alanine substitutions were consistent with the
      notion that phosphorylation at individual sites produced roughly additive
      effects, suggesting that the effect produced by phosphorylation of any one serine
      was not dependent on the phosphorylation state of other serines. These results
      are consistent with the notion that, although none of the phosphorylation sites
      studied here are absolutely necessary for activation of CFTR, individual sites
      contribute differently to the gating of the channel.

PMID- 9252550
TI  - Integrin mediation of alveolar epithelial cell migration on fibronectin and type
      I collagen.
AB  - Acute lung injury leads to type I alveolar epithelial cell (AEC) death,
      denudation of the alveolar basement membrane, and formation of an alveolar
      provisional matrix from fibronectin, fibrinogen, and type I collagen. The
      provisional matrix provides a scaffold for alveolar repair. To restore normal
      lung architecture, surviving type II AECs must reepithelialize denuded alveoli.
      We examined whether AECs migrate on provisional matrix proteins and whether
      integrins mediate this migration using a Boyden chemotaxis chamber. Cultured AECs
      migrated on fibronectin-coated filters by haptotaxis (defined as movement on a
      solid-phase substrate) more than one type I collagen-coated filters, and they did
      not migrate on fibrinogen-coated filters. Soluble fibronectin augmented migration
      on type I collagen-coated filters, but not on fibronectin-coated filters. Anti
      alpha v beta 3-integrin monoclonal antibody (MAb) inhibited migration on
      substrate-bound fibronectin by 62-77%, whereas anti-beta 1-integrin MAb inhibited
      migration by 48%. Anti-alpha 2-integrin MAb almost completely inhibited migration
      on substrate-bound type I collagen, but not on fibronectin. The novel findings in
      this study are as follows: 1) AECs migrate by haptotaxis more effectively on
      substrate-bound fibronectin than on type I collagen; 2) alpha v beta 3- and beta
      1-integrins partially mediate AEC haptotaxis on fibronectin; and 3) the alpha 2
      beta 1-integrin mediates AEC migration on type I collagen. These results support
      the importance of type II cell migration on provisional matrix proteins during
      repair of lung injury.

PMID- 9252551
TI  - Role of calcium-activated potassium channels and cyclic nucleotides on pulmonary
      vasoreactivity to serotonin.
AB  - The role of Ca(2+)-activated K+ channel modulation and cyclic nucleotide second
      messenger signal transduction in the canine pulmonary vascular response to
      serotonin was determined in the isolated blood-perfused dog lung. Pulmonary
      vascular resistances and compliances were measured using vascular occlusion
      techniques. Serotonin (10(-5) M) significantly increased precapillary and
      postcapillary resistance and significantly decreased total vascular compliance by
      decreasing large vessel compliance and middle compartment compliance.
      Tetraethylammonium ions (TEA+; 1 mM), an inhibitor of Ca(2+)-activated K+
      channels, significantly potentiated the pressor effect to serotonin on both the
      pulmonary arteries and pulmonary veins. Pretreatment with the guanosine 3',5'
      cyclic monophosphate (cGMP)/adenosine 3',5'-cyclic monophosphate (cAMP)
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-5) M), the cell
      membrane-permeable analog of cAMP, dibutyryl-cAMP (10(-5) M), or the cAMP
      dependent vasodilator isoproterenol (10(-5) M) inhibited the serotonergic
      response on both the arteries and veins, which was reversed by TEA+. In contrast,
      the stable membrane-permeable analog of cGMP, 8-bromo-cGMP (10(-5) M), had no
      effect on serotonin. These results indicate that there is a basal level of
      vasorelaxation in canine pulmonary blood vessels that is mediated by Ca(2+)
      activated K+ channel activity and that inhibition of these K+ channels increases
      pulmonary vascular tone and potentiates the pulmonary vasoactive response to
      serotonin. Also, these data suggest that cAMP-induced pulmonary vasodilation is
      mediated primarily by Ca(2+)-activated K+ channels and that activation of these
      specific K+ channels attenuates the pressor response to serotonin. Thus an
      important relationship appears to exist between the cAMP second messenger system
      and Ca(2+)-activated K+ channels in canine pulmonary vasoreactivity.

PMID- 9252552
TI  - ATP-activated basolateral Na+/H+ exchange in human normal and cystic fibrosis
      airway epithelium.
AB  - This study investigated the distribution (apical/basolateral membrane) of Na+/H+
      exchange in human nasal epithelial cell monolayers from cystic fibrosis (CF) and
      non-CF individuals. Monolayers of non-CF and CF preparations were loaded with the
      pH probe 2',7'-bis(carboxyethyl)-5(6)- carboxyfluorescein, and intracellular pH
      (pH1) was measured with a microfluorimeter. In nominally HCO3(-)-free NaCl Ringer
      solution, basal pHi values in non-CF and CF monolayers were essentially identical
      (approximately 7.1). When cells were acid loaded (NH4+ prepulse), subsequent
      alkalinization of non-CF and CF cell monolayers required serosal Na+ and was
      blocked by serosal, but not mucosal, amiloride (500 microM). In the presence of
      extracellular Na+, initial rates (delta pHi/min) of recovery from an acid load in
      non-CF and CF preparations were statistically identical (approximately 0.08).
      Pretreatment of monolayers with ATP (100 microM) or phorbol 12-myristate 13
      acetate (PMA; 100 nM) caused initial rates of recovery to increase by twofold
      over control values in both preparations. These data provide evidence in support
      for an ATP- and PMA-activated Na+/H+ exchanger located at the basolateral surface
      of airway epithelia.

PMID- 9252553
TI  - Distinct effects of SP-A and SP-B on endocytosis of SP-C by pulmonary epithelial
      cells.
AB  - Binding and endocytosis of surfactant protein (SP) C were assessed in a mouse
      pulmonary adenocarcinoma cell line, MLE-12, and in isolated rat pulmonary type II
      epithelial cells. Binding and uptake of SP-C were detected using fluorescently
      labeled SP-C and dinitrophenyl-labeled SP-C (DNP-SP-C). Endocytosis of DNP-SP-C
      was visualized by immunocytochemistry and light microscopy. Endocytosis of DNP-SP
      C occurred in MLE-12 cells, pulmonary type II epithelial cells, and NIH/3T3
      cells, indicating that uptake of SP-C does not have an absolute requirement for a
      cell-specific receptor. After 30-60 min at 37 degrees C, DNP-SP-C was
      concentrated in large intracellular bodies in MLE-12 cells. Endocytosis of DNP-SP
      C by MLE-12 cells or type II epithelial cells was decreased by SP-B or SP-B and
      SP-A together. SP-A alone did not inhibit DNP-SP-C uptake. Endocytosis of DNP-SP
      C was inhibited by a 10-fold excess of lipid vesicles containing SP-C but not by
      a 10-fold excess of lipid alone. The inhibitory effect of SP-B on SP-C uptake may
      play a role in maintaining surface-active material at the air-liquid interface.

PMID- 9252554
TI  - Mechanisms of ionomycin-induced endothelial cell barrier dysfunction.
AB  - Myosin light chain (MLC) phosphorylation catalyzed by the Ca(2+)- calmodulin
      dependent MLC kinase (MLCK) is critical to thrombin-mediated endothelial cell gap
      formation and barrier dysfunction. We have tested the hypothesis that the Ca2+
      ionophore ionomycin stimulates MLCK-dependent endothelial cell contraction and
      permeability. Ionomycin significantly increased albumin clearance and decreased
      electrical resistance across confluent bovine pulmonary microvascular and
      macrovascular endothelial cell monolayers in a concentration-dependent manner
      that was temporally similar to that produced by thrombin. In contrast, however,
      ionomycin produced a significant Ca(2+)-dependent reduction in the levels of
      phosphorylated MLC with evidence of serine/threonine phosphatase activation.
      Potential MLCK-independent mechanisms of endothelial cell permeability were
      examined with little evidence to support a role for stimulated nitric oxide
      synthase or phospholipase A2 activities. Importantly, ionomycin produced 1)
      reductions in the activities of the barrier protective adenylate cyclase and the
      adenosine 3',5'-cyclic monophosphate-dependent protein kinase A, 2) dramatic dose
      and time-dependent inhibition of endothelial cell tyrosine kinase activities,
      and 3) marked decreases in the phosphotyrosine content of the p125 focal adhesion
      kinase. These data indicate that ionomycin produces endothelial cell barrier
      dysfunction by mechanisms that are independent of MLCK activation and may involve
      reductions in endothelial cell tethering forces via inhibition of protein kinase
      A and tyrosine kinase activities, especially the p125 focal adhesion kinase.

PMID- 9252555
TI  - Systemic blood loss affects NF-kappa B regulatory mechanisms in the lungs.
AB  - The nuclear regulatory factor (NF)-kappa B is activated in the lungs of patients
      with acute respiratory distress syndrome (ARDS). In experimental models of acute
      lung injury, activation of NF-kappa B contributes to the increased expression of
      immunoregulatory cytokines and other proinflammatory mediators in the lungs.
      Because of the important role that NF-kappa B activation appears to play in the
      development of acute lung injury, we examined cytoplasmic and nuclear NF-kappa B
      counterregulatory mechanisms in lung mononuclear cells, using a murine model in
      which inflammatory lung injury develops after blood loss. Sustained activation of
      NF-kappa B was present in lung mononuclear cells over the 4-h period after blood
      loss. The activation of NF-kappa B after hemorrhage was accompanied by
      alterations in levels of the NF-kappa B regulatory proteins I kappa B alpha and
      Bcl-3. Cytoplasmic and nuclear I kappa B alpha were increased and nuclear Bcl-3
      was decreased during the first hour after blood loss, but, by 4 h posthemorrhage,
      cytoplasmic and nuclear I kappa B alpha levels were decreased and nuclear levels
      of Bcl-3 were increased. Inhibition of xanthine oxidase activity in otherwise
      unmanipulated unhemorrhaged mice resulted in increased levels of I kappa B alpha
      and decreased amounts of Bcl-3 in nuclear extracts from lung mononuclear cells.
      No changes in the levels of nuclear I kappa B alpha or Bcl-3 occurred after
      hemorrhage when xanthine oxidase activity was inhibited. These results
      demonstrate that blood loss, at least partly through xanthine oxidase-dependent
      mechanisms, produces alterations in the levels of both I kappa B alpha and Bcl-3
      in lung mononuclear cell populations. The effects of hemorrhage on proteins that
      regulate activation of NF-kappa B may contribute to the frequent development of
      inflammatory lung injury in this setting.

PMID- 9252556
TI  - IL-1 beta inhibits ET-1 production by ATII cells in vitro: evidence for
      involvement of cyclooxygenase 2 pathway.
AB  - The aim of this study was to characterize the effect of alveolar macrophage (AM)
      secretory products on endothelin (ET)-1 production by rat alveolar type II (ATII)
      cells in primary culture. We quantified preproendothelin (ppET)-1 mRNA by
      Northern blot and ET-1 concentrations in cell supernatants by enzyme-linked
      immunosorbent assay. Conditioned medium (CM) from rat adherent AM decreased the
      ppET-1 mRNA levels in ATII cells and reduced ET-1 concentrations in cell culture
      supernatants. This effect was mediated by interleukin (IL)-1 beta as shown by
      pretreatment of CM with an anti-IL-1 beta neutralizing antiserum. IL-1 beta
      effect was dependent on protein synthesis, was partially prevented with
      indomethacin, and was totally prevented with dexamethasone. Specific inhibition
      of cyclooxygenase 2 activity completely reversed the effect of IL-1 beta. We
      conclude that rat AM inhibit ET-1 production by rat ATII cells in vitro through
      IL-1 beta secretion. The IL-1 beta-mediated inhibition is dependent on the
      cyclooxygenase 2 pathway. Downregulation of ET-1 production by activated AM could
      limit the intra-alveolar burden of this profibrogenic peptide and thus could
      prevent fibrosis development.

PMID- 9252557
TI  - Protein kinase C and Ca2+ activation of mucin secretion in airway goblet cells.
AB  - Airway goblet cells secrete mucin in response to ATP and uridine 5'-triphosphate
      (UTP), but the underlying signal transduction pathways are poorly understood.
      Cultures of SPOC1 cells (L. H. Abdullah, S. W. Davis, L. Burch, M. Yamauchi, S.
      H. Randell, P. Nettesheim, and C. W. Davis. Biochem. J. 316: 943-951, 1996)
      secreted mucin on exposure to phorbol 12-myristate 13-acetate (PMA) [apparent
      affinity (K0.5) approximately 100 nM] and ionomycin (K0.5 approximately 5 microM)
      almost fivefold over baseline. Thapsigargin also elicited secretion (K0.5
      approximately 20 nM). Ionomycin and PMA together elicited approximately twice the
      secretion of either agent alone. Overnight exposure to half-maximal PMA abolished
      the response to maximal doses of UTP and PMA, whereas ionomycin was fully
      effective. Protein kinase C (PKC) activity in the membrane fraction was increased
      by maximal doses of PMA and UTP, whereas ionomycin had no effect. PKC inhibitors
      were relatively ineffective against PMA- and UTP-induced mucin secretion. Human
      and canine goblet cells in epithelial explants, by video microscopy, underwent
      exocytosis with ionomycin (1 microM) and PMA (0.1 or 1 microM). SPOC1 cell mucin
      secretion was not stimulated by forskolin, 8-(4-chlorophenylthio)-adenosine 3',5'
      cyclic monophosphate, or 8-bromoguanosine 3',5'-cyclic monophosphate. Cystic
      fibrosis transmembrane conductance regulator was not detected in SPOC1 cells by
      Western blotting, and its mRNA was detected by reverse transcriptase polymerase
      chain reaction (PCR) only as a very weak band and after 55 PCR cycles. Multidrug
      resistance (MDR1), however, was readily detected by Western blotting, and its
      mRNA was detected as a major band after 35 PCR cycles. Thus airway goblet cell
      mucin secretion, distal to receptor activation, may be regulated independently by
      Ca(2+)- and PKC-dependent pathways. Cystic fibrosis transmembrane conductance
      regulator and cyclic nucleotides, however, may not play a major role in this
      secretion.

PMID- 9252558
TI  - Furosemide-induced airway relaxation in guinea pigs: relation to Na-K-2Cl
      cotransporter function.
AB  - This study tested the hypothesis that airway relaxation to furosemide is mediated
      via the Na-K-2Cl cotransporter. If this mechanism exists in airway smooth muscle
      like in vascular smooth muscle, changes in airway relaxation should be associated
      with changes in Na-K-2Cl cotransporter function, and both should be substrate
      dependent. Tracheal rings from newborn guinea pigs were bathed in standard (STD)
      or varying low Cl- concentration ([Cl-]) N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid (HEPES). Isometric relaxation to 300 microM furosemide or 10(
      8) to 10(-5) M salbutamol was measured. Airway segments were incubated with
      rubidium-86 (86Rb) in STD or varying low [Cl-] HEPES, with and without 300 microM
      furosemide or 25 microM salbutamol. Furosemide was unable to reduce 86Rb uptake
      at 10 mM [Cl-], although relaxation was still observed in 10 mM [Cl-]. Salbutamol
      did not affect 86Rb uptake. This study demonstrated that there is a furosemide
      sensitive Na-K-2Cl cotransporter in newborn guinea pig trachea. However, the
      effect of furosemide on cotransporter function did not always directly correspond
      to differences in relaxation, suggesting that the Na-K-2Cl cotransporter may play
      a major, but not exclusive, role in furosemide-induced airway relaxation.

PMID- 9252559
TI  - Endotoxin induces endothelial barrier dysfunction through protein tyrosine
      phosphorylation.
AB  - Bacterial lipopolysaccharide (LPS) induces actin reorganization, intercellular
      gap formation, and endothelial barrier dysfunction in vitro. We studied whether
      LPS-induced increments in 14C-labeled bovine serum albumin (BSA) flux across
      bovine pulmonary artery endothelial cell (EC) monolayers and actin
      depolymerization are mediated through protein tyrosine phosphorylation. Lysates
      from EC exposed to LPS derived from Escherichia coli 0111:B4 (100 ng/ml, 1 h)
      demonstrated increased tyrosine phosphorylation of the cytoskeletal protein
      paxillin. Protein tyrosine kinase inhibition, with either herbimycin A (1 microM)
      or genistein (50 micrograms/ml), protected against LPS-induced actin
      depolymerization, intercellular gap formation, and increments in [14C]BSA flux.
      In contrast, inhibition of tyrosine phosphatases with sodium orthovanadate (2.5
      microM) or phenylarsine oxide (0.1 microM) enhanced the LPS-induced increments in
      the G-actin pool and the transendothelial flux of [14C]BSA compared with that
      seen after exposure to LPS alone. Our data indicate that the influence of LPS on
      EC actin organization and barrier function is mediated, in part, through a
      signaling pathway that is dependent on tyrosine phosphorylation.

PMID- 9252560
TI  - Glucocorticoid regulation of epithelial sodium channel genes in human fetal lung.
AB  - Pulmonary epithelial Na+ channels (ENaC), composed of three distinct subunits
      (alpha, beta, and gamma), play a critical role in the regulation of fluid
      reabsorption from airspaces of late-gestation fetal lung. We studied the
      expression of ENaC subunit genes in cultured human fetal lung. All three mRNAs
      were expressed at low levels in second trimester lung (13-32% of adult values at
      24 wk gestation). There was a spontaneous increase of approximately threefold
      over preculture values of all three subunits within 24 h of explant culture in
      serum-free Waymouth's medium. Dexamethasone (Dex) induced all three mRNAs by two-
      to threefold. Maximal induction was noted by 8 h with 30-100 nM Dex and half
      maximal stimulation with 3-10 nM Dex. Cycloheximide decreased basal expression of
      all three subunits by 8 h but did not alter the response to Dex. Actinomycin D
      and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), inhibitors of RNA
      polymerase II, decreased the basal and the Dex-induced expression of all three
      subunits with a more marked effect on human hENaC-gamma than on hENaC-alpha or
      hENaC-beta. Under conditions where transcription was blocked by actinomycin D or
      DRB, Dex did not alter the stability of the three mRNAs. Triiodothyronine (T3) at
      low (2 nM) or high (100 nM) concentrations had no effect on the expression of the
      three subunits in the presence or absence of low (10 nM) or high (100 nM)
      concentrations of Dex for 8 or 24 h. Similarly, 8-bromoadenosine 3',5'-cyclic
      monophosphate (2 microM) had no effect on basal or Dex-induced increase in the
      three subunits. We conclude that the three Na+ channel subunit genes are
      expressed in second trimester human fetal lung and are coordinately upregulated
      by glucocorticoid hormones but not by T3 or adenosine 3',5'-cyclic monophosphate.
      Glucocorticoid induction is receptor mediated, is primarily transcriptional, and
      does not require the induction of an intermediate protein for transcriptional
      enhancement. We speculate that induction of lung ENaC may contribute to the
      beneficial effects of antenatal glucocorticoids in premature babies.

PMID- 9252562
TI  - Differential expression of Na-K-ATPase isoforms in rat alveolar epithelial cells.
AB  - Lung Na-K-ATPase has been shown to contribute to vectorial Na+ transport and
      edema clearance. The alpha 1- and beta 1-Na-K-ATPase subunits have been localized
      to alveolar type II (ATII) cells, and the alpha 2-Na-K-ATPase has been reported
      in rat lung homogenates. Expression of Na-K-ATPase alpha 1-, alpha 2-, and beta 1
      subunits was investigated in rat ATII cells cultured for 7 days, a period during
      which they lose their phenotypic markers and differentiate to an alveolar type I
      (ATI)-like cell phenotype. Differentiation of ATII cells to an ATI-like phenotype
      resulted in a decrease of alpha 1- and an increase of alpha 2-mRNA and protein
      abundance without changes in the beta 1-subunit. Thus ATI-like cells exhibited a
      mixture of alpha 1- and alpha 2-isoforms. Nuclear run-on analysis suggests that
      these changes were transcriptionally regulated. The existence of the distinct
      functional classes of Na-K-ATPase in ATII and ATI-like cells was confirmed by
      ouabain inhibition of Na-K-ATPase activity. Ouabain inhibition of ATII cells was
      consistent with expression of the alpha 1-isozyme [50% inhibitory concentration
      (IC50) = 4 x 10(-5) M], whereas, in ATI-like cells, it was consistent with the
      presence of both alpha 1- and alpha 2-isozymes (IC50 = 9.0 x 10(-5) and 1.5 x 10(
      7) M, respectively); [3H]ouabain binding studies corroborated these findings. Our
      results indicate that, during ATII cell cytodifferentiation with time in culture,
      there is a shift in isoform composition that may reflect physiological functions
      of alveolar epithelial cells.

PMID- 9252561
TI  - Pulmonary artery smooth muscle cells from chronically hypoxic neonatal calves
      retain fetal-like and acquire new growth properties.
AB  - Growth properties retained and acquired by immature pulmonary artery (PA) smooth
      muscle cells (SMC) in vivo after chronic exposure to hypoxia and the mechanisms
      that regulate hypoxia-induced change in proliferative phenotype are not known. We
      tested the hypothesis that PA SMC from neonatal calves exposed to hypoxia after
      birth would both retain fetal-like and acquire new growth characteristics and
      that these changes would be at least partially dependent on protein kinase C
      (PKC), a key proproliferative signal transduction pathway. Like fetal cells, PA
      SMC from hypoxic calves grew faster in the presence and absence of serum and were
      more responsive to insulin-like growth factor I and platelet-derived growth
      factor-BB than control neonatal and adult cells. PA SMC from hypoxic calves also
      acquired other growth properties (i.e., including increased hypoxic growth after
      PKC activation) that were new compared with those observed for fetal cells. The
      proliferative response to hypoxia was first detectable in the neonatal period and
      was further increased in cells from hypoxic calves. SMC from fetuses and hypoxic
      calves were more susceptible to the growth-inhibiting effects of PKC antagonists
      (dihydrosphingosine and calphostin C) than control neonatal and adult cells. To
      test if the Ca(2+)-dependent isozymes of PKC were uniquely important in the
      developmental and acquired growth changes observed, the antagonistic effect of
      the specific, but isozyme nonselective, PKC inhibitor Ro-81-8220 was then
      compared with GF-109203X, a structural analog with relative specificity for the
      Ca(2+)-dependent isozymes of PKC (alpha and beta in PA SMC). The faster growing
      PA SMC from bovine fetuses and hypoxia-exposed calves again demonstrated greater
      growth inhibition in response to both inhibitors. GF-109203X was equipotent to Ro
      31-8220, and its antiproliferative effects were shown to not be due to an
      increase in apoptosis. Phorbol ester-induced PKC downregulation, another
      inhibitor strategy that selectively depletes bovine PA SMC of PKC-alpha, but not 
      beta, mimicked the antiproliferative effects of GF-109203X. Whole cellular PKC
      catalytic activity paralleled the pattern of peptide-induced growth and
      susceptibility to PKC inhibition. These results suggest that PA SMC from hypoxia
      exposed neonatal calves retain enhanced fetal-like proliferative capacity and
      acquire new growth properties that are at least partially dependent on the Ca(2+)
      regulated isozymes of PKC and in particular PKC-alpha.

PMID- 9252563
TI  - Expression of integrin cell adhesion receptors during human airway epithelial
      repair in vivo.
AB  - Airway epithelium is subject to injury during inflammation and exposure to a
      variety of inhaled and infectious agents. Little is known about the expression of
      integrins during human airway epithelial regeneration and differentiation after
      injury. We therefore characterized integrin subunit expression after mechanical
      injury in an in vivo xenograft model of human bronchial epithelium. On the
      migrating cells at the edges of surface epithelial wounds, there was increased
      expression of the alpha v-, beta 5-, beta 6-, and alpha 5-integrin subunits.
      During the later phase of repair, the increased expression of alpha v-, beta 5-,
      and beta 6-subunits persisted, but the expression of the beta 8-subunits was
      restricted to basal cells. In addition, there was a redistribution of the alpha 2
      and alpha 6-collagen/laminin-binding integrins to suprabasal epithelial layers.
      There was no expression of the beta 3- or alpha 4-integrin subunit on reparative
      epithelium. A similar upregulation of alpha v-, beta 5-, and beta 6-integrin
      receptor subunits was observed in areas of undifferentiated airway from cystic
      fibrosis patients. Injured epithelium was found to be significantly more
      susceptible to gene transfer with a recombinant adenovirus, suggesting that the
      increased integrin expression has implications for the acquisition of adenovirus
      infections and for lung-directed gene therapy.

PMID- 9252564
TI  - Pulmonary clearance and release of norepinephrine and epinephrine in newborn
      lambs.
AB  - To examine the pulmonary kinetics of the catecholamines norepinephrine and
      epinephrine immediately after birth, eight fetal lambs were instrumented with
      vascular catheters under general anesthesia at 133-134 days gestation (term = 147
      days) and were delivered by cesarean section 1 wk later. Pulmonary norepinephrine
      and epinephrine kinetics were then studied 1 and 4 h after birth using
      radiotracer dilution methodology. The pulmonary fractional extraction of
      norepinephrine was similar in 1-h (0.111 +/- 0.021) and 4-h (0.117 +/- 0.023)
      lambs and constituted 24 +/- 5 and 32 +/- 9% of total body norepinephrine
      clearance, respectively. Pulmonary removal of epinephrine was less pronounced
      with a fractional extraction of 0.035 +/- 0.017 in 1-h and 0.036 +/- 0.013 in 4-h
      lambs, which corresponded to 8 +/- 4 and 9 +/- 3% of total body epinephrine
      clearance, respectively. Pulmonary spillover of norepinephrine into the
      circulation was similar in 1-h (79 +/- 26 ng.min-1.kg-1) and 4-h (82 +/- 18
      ng.min-1.kg-1) lambs, and this comprised 27 +/- 8 and 42 +/- 8% of total body
      norepinephrine spillover, respectively. Pulmonary epinephrine spillover was not
      detectable at 1 h, but it occurred in all 4-h lambs, averaging 4.7 +/- 0.8 ng.min
      1.kg-1 or 20 +/- 6% of epinephrine total body spillover. These findings indicate
      that the lungs of newborn lambs 1) are a major site for removal of norepinephrine
      and epinephrine from the circulation; 2) release a substantial quantity of
      norepinephrine into the circulation, consistent with the presence of tonic
      pulmonary sympathetic nerve activity; and 3) constitute a significant extra
      adrenal source of plasma epinephrine.

PMID- 9252565
TI  - Differential nitric oxide production by microvascular and macrovascular
      endothelial cells.
AB  - Phenotypic heterogeneity among endothelial cell populations may account for
      important organ-specific behaviors. Experimental evidence suggests that
      endothelium-derived nitric oxide mediates certain of these unique responses. The
      purpose of these investigations was to compare rat pulmonary microvascular
      endothelial cells with pulmonary artery and aortic macrovascular endothelial
      cells in their ability to generate nitric oxide (NO). Cultures of these
      microvascular and macrovascular endothelial cells were incubated with interferon
      gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and Salmonella
      typhimurium lipopolysaccharide (LPS) alone or in combination, and nitrite
      production was measured. Single-agent exposure with IFN-gamma (up to 1,000 U/ml),
      TNF-alpha (up to 60,000 U/ml), or LPS (up to 500 ng/ml) had little effect on
      nitrite generation. Nitrite production by rat aortic macrovascular endothelial
      cells (RAEC) was significantly greater than that by the rat lung microvascular
      endothelial cells (RLMVEC) when stimulated with TNF-alpha + IFN-gamma, LPS + IFN
      gamma, or TNF-alpha + LPS. The maximal response by all endothelial cell types
      (approximately 15-fold increase in RAEC and 8-fold increase in RLMVEC) was
      observed with LPS + IFN-gamma. The nitrite generation from rat pulmonary artery
      endothelial cells was intermediate between RAEC and RLMVEC responses when
      stimulated with IFN-gamma + LPS or TNF-alpha. Similar patterns of heterogeneous
      inducible nitric oxide synthase mRNA induction occurred when Northern analysis of
      specimens from the cultured endothelial cell types was done. These data suggest
      that phenotypic heterogeneity between these endothelial cell populations is
      substantial and, by inference, that site-specific NO. generation may occur.

PMID- 9252566
TI  - Matrix Gla protein gene expression is induced by transforming growth factor-beta
      in embryonic lung culture.
AB  - Matrix Gla protein (MGP) is a vitamin K-dependent extracellular matrix protein
      with a wide tissue distribution. The current study was designed to investigate
      the possible regulation of MGP by exogenous transforming growth factor-beta (TGF
      beta) during lung development. Using reverse transcription coupled competitive
      polymerase chain reaction methodology, we determined that exogenous TGF-beta 1
      increases MGP mRNA levels in embryonic mouse lung culture in a concentration
      dependent manner. MGP mRNA levels were elevated by 5.0-fold at 50 ng/ml TGF-beta
      1 in E11 embryonic mouse lungs explanted for 4 days in serumless culture. MGP
      mRNA stimulation by TGF-beta 1 was a time-dependent event: MGP message increment
      was initially detected after 1 day in culture, and MGP mRNA levels continued to
      increase up to 4 days in the presence of TGF-beta 1. In addition, embryonic lungs
      in serumless medium without exogenously added TGF-beta 1 showed an increase,
      although to a lesser extent, in pulmonary MGP mRNA level during culture,
      indicating that MGP expression is also developmentally regulated. The present
      results indicate that MGP gene expression can be stimulated by exogenous TGF-beta
      1 during early embryonic mouse lung branching morphogenesis in culture.

PMID- 9252567
TI  - Regulation of nitrogen fixation by different nitrogen sources in the filamentous
      non-heterocystous cyanobacterium Microcoleus sp.
AB  - The pattern of N2 fixation, the synthesis and activity of nitrogenase under
      different nitrogen sources was studied in the filamentous, non-heterocystous
      cyanobacterium Microcoleus sp. grown under defined culture conditions. Cells
      grown under a 10 h light/14 h dark (10L/14D) cycle with N2 as an inorganic
      nitrogen source showed highest nitrogenase activity (acetylene reduction) at the
      end of the light phase and then a decrease after entering the dark phase.
      Nitrogenase synthesis was neither suppressed after 7 days of growth with 2 mM
      NaNO3 or 0.2 mM (NH4)2SO4 or 0.3 mM urea nor with 20 mM NaNO3 or 3 mM (NH4)2SO4
      or 4 mM urea under the 10L/14D cycle. Western immunoblots tested with polyclonal
      antisera against the Fe-protein revealed the following: (1) the Fe-protein was
      synthesized in cells grown with N2 as well as in cells grown with NaNO3 or
      (NH4)2SO4 under the 10L/14D cycle; (2) the Fe-protein was found in cells grown
      with urea under the 10L/14D cycle, but not in the darkness; (3) only one protein
      band, corresponding to the Fe-protein, was found in cells harvested during the
      light phase of the 10L/14D cycle under the tested conditions. No nitrogenase
      activity was observed when chloramphenicol was added to the cultures 4 h before
      the onset of the light period. This observation suggest de novo synthesis of
      nitrogenase in Microcoleus sp.

PMID- 9252568
TI  - Fluorescent measurement of the intracellular pH during sporulation of
      Saccharomyces cerevisiae.
AB  - This work reports the intracellular pH (pHi) dynamics of Saccharomyces cerevisiae
      cells in sporulation medium. Cells loaded with the pH-sensitive dye carboxy
      seminaphthorhodafluor-1 (C.SNARF-1) exhibited an alkalization of the pHi
      following the extracellular pH during sporulation in the absence of buffer and
      almost no change in pHi or delta pH when sporulation was carried out in buffered
      medium. The results indicate that the pH gradient does not appear to be directly
      involved in the regulation of acetate uptake during sporulation. However, the
      alkalization of pHi by eliciting a decrease in metabolic fluxes could account for
      a lower demand for acetate.

PMID- 9252569
TI  - In vivo reaction of affinity-tag-labelled epidermin precursor peptide with
      flavoenzyme EpiD.
AB  - The Staphylococcus epidermidis genes encoding the His-tag-labelled epidermin
      precursor peptide EpiA and the flavoenzyme EpiD or the mutant protein EpiD-G93D,
      which lacks the coenzyme, were co-expressed and the proteins were synthesized in
      vivo in Escherichia coli. Only in the presence of EpiD was the precursor peptide
      converted to a reaction product with a decrease in mass of 44-46 Da. This result
      confirms the in vitro experiments carried out with purified EpiA and purified
      EpiD from Staphylococcus epidermidis [Kupke et al. (1994) J. Biol. Chem. 269,
      5653-5659]. EpiD catalyzes the oxidative decarboxylation of the C-terminal
      cysteine residue of EpiA to a [Z]-enethiol structure. In the presence of EpiD,
      the amount of purified (modified) peptide EpiA was several-fold higher than in
      the presence of EpiD-G93D, indicating that the stabilization of EpiA against
      proteolysis is due to an interaction with EpiD or to the presence of the C
      terminal modification. The presented experimental approach will be valuable for
      the analysis of enzymes that catalyze posttranslational modification reaction of
      peptides and proteins.

PMID- 9252570
TI  - SEF17 fimbriae are essential for the convoluted colonial morphology of Salmonella
      enteritidis.
AB  - Salmonella enteritidis isolated from poultry infections generated a convoluted
      colonial morphology after 48 h growth on colonisation factor antigen (CFA) agar
      at 25 degrees C. A mutant S. enteritidis defective for the elaboration of the
      SEF17 fimbrial antigen, in which the agf gene cluster was inactivated by
      insertion of an ampicillin resistance gene cassette, and other wild-type S.
      enteritidis transduced to this genotype failed to produce convoluted colonies.
      However, growth of SEF17- mutants at 25 degrees C on CFA agar supplemented with
      0.001% Congo red resulted in partial recovery of the phenotype. Immunoelectron
      microscopy demonstrated that copious amounts of the SEF17 fimbrial antigen were
      present in the extracellular matrix of convoluted colonies of wild-type virulent
      S. enteritidis isolates. Bacteria were often hyperflagellated also.
      Immunoelectron microscopy of SEF17- mutants grown on CFA agar+0.001% Congo red
      demonstrated the elaboration of an as yet undefined fimbrial structure. Isolates
      of S. enteritidis which were described previously as avirulent and sensitive to
      environmental stress failed to express SEF17 or produce convoluted colonies.
      These data indicate an essential role for SEF17, and possibly for another fimbria
      and flagella, in the generation of the convoluted colonial phenotype. The
      relationship between virulence and colonial phenotype is discussed.

PMID- 9252571
TI  - A helicase gene (helO) in Rhizobium meliloti WSM419.
AB  - A 2.8 kb BamHI DNA fragment adjacent to a BamHI fragment containing actR-actS (a
      sensor/regulator pair required for low pH tolerance in Rhizobium meliloti WSM419)
      was cloned and sequenced. A computer predicted protein of 821 amino acids,
      designated HelO, showed extensive similarity with 'DEAH' motif helicases.
      Expression of helO was higher at pH 7.0 than pH 5.8 and it did not require the
      product of the actR gene. Inactivation of helO by insertion of a omega interposon
      at codon 40 did not affect nodulation, growth or tolerance to low pH, high
      temperature, osmolarity or elevated levels of copper or zinc.

PMID- 9252572
TI  - Characterization of fluoranthene- and pyrene-degrading Mycobacterium-like strains
      by RAPD and SSU sequencing.
AB  - Bacterial isolates were obtained from two sites in New Zealand contaminated with
      polycyclic aromatic hydrocarbons. Isolates capable of degrading polycyclic
      aromatic hydrocarbons were characterized in two mycobacterial groups according to
      phenotypic properties. These groups were supported by random amplified
      polymorphic DNA analysis. Nucleotide sequences of 16S ribosomal RNA genes from
      isolates representing each group were determined and compared with other
      mycobacterial 16S ribosomal RNA sequences. The taxonomic relationships of these
      isolates are considered.

PMID- 9252574
TI  - Suppression of Francisella tularensis growth in the rat by co-infection with F.
      novicida.
AB  - We have previously shown that when cultured in vitro, peritoneal rat macrophages
      infected with Francisella novicida spontaneously release nitric oxide in
      sufficient quantities to inhibit bacterial growth. However, it is not known
      whether F. novicida can have a similar antimicrobial effect in vivo. Here we show
      that a co-infection of F. novicida with Francisella tularensis can suppress the
      number of F. tularensis cells in rat spleens by as much as 100-fold.

PMID- 9252573
TI  - Analysis of non-polar deletion mutations in the genes of the spo0K (opp) operon
      of Bacillus subtilis.
AB  - The spo0K (opp) operon of Bacillus subtilis encodes an oligopeptide permease that
      is required for uptake of oligopeptides, development of genetic competence, and
      initiation of sporulation. We made in-frame, non-polar deletion mutations in each
      of the first four genes of the five-gene spo0K operon and tested effects on
      oligopeptide transport, sporulation, and expression of competence genes. spo0KA,
      B, C, and D were required for sporulation, competence development, and
      oligopeptide transport. Disruption of spo0KE caused a less severe phenotype than
      did disruption of any of the other genes of the operon.

PMID- 9252575
TI  - The Saccharomyces cerevisiae acetyl-coenzyme A synthetase encoded by the ACS1
      gene, but not the ACS2-encoded enzyme, is subject to glucose catabolite
      inactivation.
AB  - In Saccharomyces cerevisiae, the structural genes ACS1 and ACS2 each encode an
      isoenzyme of acetyl-CoA synthetase (ACS; EC 6.2.1.1). Involvement of glucose
      catabolite repression in regulation of the two isoenzymes was investigated by
      following ACS activity after glucose pulses (100 mM) to ethanol-limited chemostat
      cultures. In wild-type S. cerevisiae and in an isogenic strain in which ACS2 had
      been disrupted, ACS activity decreased after a glucose pulse. No such
      inactivation was observed in a strain in which ACS1 was disrupted. Western blots
      demonstrated that the ACS1 product, but not the ACS2 product, was degraded after
      a glucose pulse. Inactivation kinetics of the ACS1 product resembled those of
      isocitrate lyase.

PMID- 9252576
TI  - Production of bleomycin N-acetyltransferase in Escherichia coli and Streptomyces
      verticillus.
AB  - Bleomycin-producing Streptomyces verticillus ATCC 15003 has two bleomycin
      resistance genes, designated blmA and blmB. Bleomycin N-acetyltransferase,
      encoded by blmB, was overproduced in Escherichia coli as a protein fused to the
      maltose-binding protein. The protein (fBAT), purified to homogeneity after
      digestion of the fusion product with blood coagulation factor Xa protease, had an
      additional 6 N-terminal amino acid residues, but retained its bleomycin
      acetylating activity, as did the entire fusion protein. The K(m) and Vmax values
      of purified fBAT for the substrate bleomycin were 13.0 microM and 3.4 nmol
      [corrected] min-1 ml-1, respectively. The optimal pH for the acetylating activity
      was 6.0 in 10 mM phosphate buffer. The molecular mass and pI value of fBAT were
      estimated by polyacrylamide gel electrophoresis to be about 34500 and 6.13,
      respectively. An anti-fBAT monoclonal antibody was generated and used to show
      that bleomycin N-acetyltransferase is expressed simultaneously with bleomycin
      production in S. verticillus.

PMID- 9252577
TI  - Physiological and morphological effects of genetic alterations leading to a
      reduced synthesis of UDP-glucose in Saccharomyces cerevisiae.
AB  - Yeast cells lacking UDP-Glc pyrophosphorylase (UGPase) encoded by UGPI are not
      viable. Two strategies were developed to drastically reduce the intracellular
      concentration of UDP-Glc in order to study the consequences of this metabolic
      engineering on physiology and morphology. Firstly, UGP1 was placed under the
      strongly regulatable THI4 promoter. This resulted in a 95% reduction of UGPase
      activity in the presence of thiamine. The phenotypic effects of this reduction
      were slightly stronger than those of glucose on the GALI0/CYC1-UGP1 gene fusion
      [Daran et al. (1995) Eur. J. Biochem. 230, 520-530]. A further reduction of flux
      towards UDP-Glc was achieved by deletion of the two phosphoglucomutase genes in
      the ugp1 conditional strain. The growth of this new mutant strain was hardly
      affected, while it was extremely sensitive to cell wall interfering drugs.
      Surprisingly, UDP-Glc levels were reduced only by 5-fold, causing a proportional
      decrease in both glycogen and beta-glucans. Taken altogether, these results
      indicate that a few percent of enzymatic activities leading to the formation of
      UDP-Glc appears sufficient to provide the UDP-Glc demands required for cell
      viability, and that the loss of function of UGP1 is lethal mainly because of the
      inability of yeast cells to properly form the cell wall.

PMID- 9252578
TI  - Effect of carbon source on the expression of celA1, a cellulase-encoding gene
      from Streptomyces halstedii JM8.
AB  - The production of the cellulase Cell from Streptomyces halstedii JM8 was studied
      in cells grown in the presence of glucose, cellobiose or microcrystalline
      cellulose (Avicel). Among these, glucose repressed expression while cellobiose
      and Avicel exerted a clear induction. The gene celA1 was cloned in several
      heterologous Streptomyces hosts and its expression analyzed. S. parvulus
      transformed with the plasmid pJM11, a pIJ702 derivative, was the best producer. A
      region which includes the sequence ATTGGGACCGCTTCC located between positions -161
      and -147 upstream from the translation initiation codon [Fernandez-Abalos et al.
      (1992) J. Bacteriol. 174, 6368-6376] was deleted and its effect was studied in
      the presence of different carbon sources. Although the observed effect depends on
      the host used, this region seems to be involved in activation of the expression
      of this gene.

PMID- 9252579
TI  - Degradation studies on Escherichia coli capsular polysaccharides by
      bacteriophages.
AB  - The serologically and structurally related Eschrichia coli capsular
      polysaccharides (K antigens) K13, K20, and K23 were found to be depolymerized by
      the bacteriophages phi K13 and phi K20 to almost similar oligomer profiles as
      shown by polyacrylamide gel electrophoresis. The phage-polysaccharide
      interactions were followed by an increase of reducing 2-keto-3-deoxyoctulosonic
      acid due to a phage-associated glycanase that catalyzed the hydrolytic cleavage
      of common beta-ketopyranosidic 2-keto-3-deoxyoctulosonic acid linkages. The
      related E. coli K antigens K18, K22, and K100 as well as the Haemophilus
      influenzae type b capsular polysaccharide were degraded by bacteriophage phi K100
      with different efficacy. It is suggested that phi K100 enzymatically cleaves
      ribitol-5-phosphate bonds as the only structural feature present in all the
      polysaccharides investigated.

PMID- 9252580
TI  - Transcriptional analysis of the sigA and sigB genes of Brevibacterium
      lactofermentum.
AB  - Transcription of the sigA and sigB genes of Brevibacterium lactofermentum,
      encoding the principal sigma factors of RNA polymerase, has been investigated by
      Northern blot and primer extension analysis. Northern hybridizations revealed
      that sigA is transcribed as a monocistronic mRNA of 1.7 kb and sigB gives two
      transcripts of 1.1 and 1.5 kb. Similar transcription patterns of sigA and sigB
      genes in nutrient-rich medium were observed; transcripts of both genes occurred
      simultaneously throughout the exponential growth phase and decayed clearly when
      the stationary phase was reached. Primer extension analysis of B. lactofermentum
      RNA showed that the sigA and sigB transcription initiation sites are located 17
      bp and 24 bp upstream from the first nucleotide of the respective translation
      initiation codons. Alignment of the sigA and sigB promoter regions provided
      evidence for highly conserved sequences in both of them.

PMID- 9252581
TI  - Characterization of flaA- and flaB- mutants of Serpulina hyodysenteriae: both
      flagellin subunits, FlaA and FlaB, are necessary for full motility and intestinal
      colonization.
AB  - Motility of Serpulina hyodysenterlae is thought to play a pivotal role in the
      enteropathogenicity of this spirochete. To test this, a series of isogenic
      mutants containing specifically disrupted flagellar alleles (flaA1 and flaB1)
      were constructed and examined for virulence and ability to colonize the
      intestinal tract of mice. Mice challenged with the wild-type, parent strain
      showed a dose-related response to the challenge organism. In contrast, all
      flagellar mutant strains demonstrated aberrant motility in vitro and a
      significantly reduced ability to colonize and infect mice. To some extent, this
      degree of reduction in colonizing ability was dependent on the wild-type
      background strain used for mutant construction. A flaB1- strain generated from a
      'laboratory isolate' was unable to colonize the mouse gut even at high challenge
      doses, although its parent was virulent for mice. However, when the same parent
      strain was 'animal-passed' prior to disruption of flaB1, the resulting flaB1-
      strain was able to transiently colonize the mouse gut and induce intestinal
      lesions. A comparison of a series of flagellar mutants constructed using the
      animal-passed parent strain further revealed that specific inactivation of flaB1
      resulted in a more pronounced reduction in virulence and colonizing ability than
      that which occurred with two flaA1 mutants. Taken together, these data suggest
      that motility is an essential virulence factor of S. hyodysenteriae and that both
      sheath and core flagellin subunits, FlaA and FlaB, are necessary for full
      motility and intestinal colonization.

PMID- 9252582
TI  - Identification and characterization of the gyrB gene from Treponema pallidum
      subsp. pallidum.
AB  - The nucleotide sequence of a DNA gyrase B subunit gene (gyrB) from Treponema
      pallidum has been determined. Southern blot analysis of T. pallidum chromosomal
      DNA indicated that this gene is present as a single copy. The organization of
      genes flanking the gyrB gene is unique in comparison to that of other bacteria.
      The gyrB gene encodes a 637 amino acid protein whose deduced sequence has a high
      degree of homology with type-II topoisomerase ATPase subunits (GyrB and ParE).
      Five type-II topoisomerase motifs, an ATP-binding site (Walker A), and amino acid
      residues that putatively interact with ATP, are highly conserved in the T.
      pallidum GyrB protein.

PMID- 9252583
TI  - Neomycin- and spectinomycin-resistance replacement vectors for Bacillus subtilis.
AB  - A plasmid is described for Bacillus subtilis that facilitates replacement of the
      widely used neomycin resistance gene (neo) with a spectinomycin resistance (spcE)
      gene. A second plasmid is described that facilitates replacement of spcS,
      associated with mini-Tn10 mutagenesis in B. subtilis, with neo. These plasmids
      can also function as integrative vectors for B. subtilis. They expand the scope
      of strain construction and gene analysis in B. subtilis.

PMID- 9252584
TI  - Replication and amplification of lambda plasmids in Escherichia coli during amino
      acid starvation and limitation.
AB  - It was demonstrated previously that replication of plasmids derived from
      bacteriophage lambda (so-called lambda plasmids) is inhibited in wild-type
      Escherichia coli cells starved for isoleucine and arginine whereas it proceeds
      under the same conditions in relA mutants. Since replication of other replicons
      during the stringent or relaxed response depends on the nature of the deprived
      amino acid, we investigated replication of lambda plasmids in E. coli relA+ and
      relA- strains starved for different amino acids. We found that replication of
      lambda plasmids is generally inhibited during the stringent, but not relaxed,
      response. Differences between cells starved for different amino acids, although
      reproducible, were not dramatic. Amino acid starvation was previously proposed as
      a method for amplification of lambda plasmid DNA in vivo. We found that during
      amino acid limitation lambda plasmids replicate more extensively in the relA
      mutants than during amino acid starvation. The efficiency of plasmid DNA
      amplification was found to be dependent on the kind of limited amino acid; in
      relA- bacteria limited for leucine we observed about 10-fold plasmid
      amplification. Some lambda plasmid replication was also found under these
      conditions in the relA+ host. The mechanism of the stringent control of lambda
      plasmid DNA replication has already been proposed. Here the possible mechanism of
      the regulation of lambda plasmid replication during amino acid limitation is
      presented.

PMID- 9252585
TI  - Detection and in situ identification of representatives of a widely distributed
      new bacterial phylum.
AB  - 16S rRNA gene libraries were prepared by polymerase chain reaction amplification
      and cloning from soil samples taken periodically from a field with genetically
      modified plants. Sequence analyses of the cloned rDNAs indicated that 140 of them
      clustered apart from known bacterial phyla. Based on 31 full sequences a new
      phylum could be defined. It includes Holophaga foetida, 'Geothrix fermentans' and
      Acidobacterium capsulatum as the only cultured species so far. Therefore, this
      line of descent was named the Holophagal Acidobacterium phylum. About 50
      published partial sequences of cloned rDNAs retrieved from soil, freshwater
      sediments or activated sludge from different continents indicate the occurrence
      of further representatives of this phylum. Two specific hybridization probes were
      constructed for members of one of four subclusters. A careful data analysis
      revealed the importance and problems of identifying and dealing with artefacts
      such as chimeric structure when defining new phylogenetic groups based mainly
      upon cloned amplified rDNAs. For the first time, the presence of bacterial cells
      representing this group could be shown in soil, sediment, activated sludge and
      lake snow by in situ hybridization.

PMID- 9252586
TI  - Identification and phylogenetic analysis of Lactobacillus using multiplex RAPD
      PCR.
AB  - Multiplex RAPD-PCR was used to generate unique and identifying DNA profiles for
      isolates of the genus Lactobacillus. The method that was used was based on the
      combination of two 10-mer oligonucleotides in a single PCR. The generated RAPD
      profiles enabled discrimination of all lactobacillus strains that were used in
      this study. A dendrogram was generated from the RAPD profiles. The results of
      genetic relatedness obtained from the dendrogram were compared with the results
      obtained using carbohydrate fermentation profiles. Most of the gastrointestinal
      isolates studied could not be grouped using carbohydrate fermentation profiles.
      The RAPD profiles provided sufficient information to prepare a dendrogram of
      genetic relatedness. The gastrointestinal isolates were clustered together on the
      dendrogram. Furthermore an isolate originating from the stomach (strain ML004)
      was closely related to Lactobacillus fermentum. It was concluded that multiplex
      RAPD-PCR was useful for characterisation and inference of relatedness of
      Lactobacillus isolates.

PMID- 9252587
TI  - Acridine orange as an indicator of bacterial susceptibility to gentamicin.
AB  - We have studied the response of Escherichia coli NCTC10418 to gentamicin with
      flow cytometry. The susceptibility of individual bacterial cells to the
      antibiotic was assessed by differential staining using the metachromatic dye,
      acridine orange. Exponential phase cultures were exposed to the minimum
      bactericidal concentration of gentamicin and analysed at regular intervals over
      90 min. Within 60 min of exposure to the drug, two sub-populations of organisms
      could be distinguished in cultures by their different acridine orange-associated
      fluorescence emissions of < 550 nm and > 550 nm. The number of bacteria
      exhibiting acridine orange-associated fluorescence at > 550 nm corresponded to
      counts of colony forming units.

PMID- 9252588
TI  - Molecular cloning of actin genes in Trichomonas vaginalis and phylogeny inferred
      from actin sequences.
AB  - The parasitic protozoan Trichomonas vaginalis is known to contain the ubiquitous
      and highly conserved protein actin. A genomic library and a cDNA library have
      been screened to identify and clone the actin gene(s) of T. vaginalis. The
      nucleotide sequence of one gene and its flanking regions have been determined.
      The open reading frame encodes a protein of 376 amino acids. The sequence is not
      interrupted by any introns and the promoter could be represented by a 10 bp motif
      close to a consensus motif also found upstream of most sequenced T. vaginalis
      genes. The five different clones isolated from the cDNA library have similar
      sequences and encode three actin proteins differing only by one or two amino
      acids. A phylogenetic analysis of 31 actin sequences by distance matrix and
      parsimony methods, using centractin as outgroup, gives congruent trees with
      Parabasala branching above Diplomonadida.

PMID- 9252589
TI  - Pseudomonas tolaasii: extra-genomic factor mediates toxin production and
      efficiency.
AB  - Pseudomonas tolaasii is responsible for brown blotch symptoms on Agaricus
      bisporus. Investigations among 15 P. tolaasii wild-type strains revealed the
      existence of an extra-genomic factor. Pseudomonas tolaasii CNBP2152D, a
      spontaneous derivative of the wild-type strain CNBP2152 which has lost the
      factor, exhibited a significant decline in pathogenicity. Comparison of blotch
      symptoms induced by toxins extracted from CNBP2152 and CNBP2152D showed that the
      extragenomic factor mediates toxin production and efficiency.

PMID- 9252590
TI  - Analysis of CcpA mutations defective in carbon catabolite repression in Bacillus
      megaterium.
AB  - Five mutations in ccpA of Bacillus megaterium with impaired functions were
      analysed for carbon catabolite repression. The phenotypes support the hypothesis
      that CcpA assumes a PurR/LacI fold. The completely inactive mutants CcpA119GE and
      CcpA326am cause alterations which are incompatible with that fold. A mutation
      with reduced activity, CcpA81GE, affects a site that would be partially surface
      exposed and may interfere with structure formation or cofactor binding. A
      mutation in the putative hinge alpha-helix, CcpA52AE, is negative transdominant
      over wild-type ccpA. The mutant CcpA38am is inactive, although reduced amounts of
      wild-type size protein are produced.

PMID- 9252592
TI  - Block of the cell cycle of the yeast Saccharomyces cerevisiae by tyrphostin, an
      inhibitor of protein tyrosine kinase.
AB  - Tyrphostins are inhibitors of the epidermal growth factor receptor tyrosine
      kinase. To elucidate the biological function of protein tyrosine kinases in yeast
      cells, a mutant hypersensitive to tyrphostin was isolated and investigated for
      its response to the drug. The mutation was recessive and was designated tpt1 for
      tyrphostin hypersensitive. A tpt1 strain cannot grow in the presence of
      tyrphostin, implying that a biological process sensitive to tyrphostin is
      essential for cell growth. Microscopic observation indicated that large-budded
      cells were accumulated in the presence of the inhibitor. The results suggest the
      involvement of protein tyrosine phosphorylation in the cell cycle progression of
      Saccharomyces cerevisiae.

PMID- 9252591
TI  - The rate of antigenic variation in fly-transmitted and syringe-passaged
      infections of Trypanosoma brucei.
AB  - Rates of antigenic variation were measured in vivo in several populations of
      cloned lines of Trypanosoma brucei before and after cyclical transmission through
      tsetse flies. Two cloned lines were adapted for use in laboratory conditions by
      extensive syringe passaging and rates of antigenic switching/cell/generation were
      less than 3 x 10(-6) and 1 x 10(-4) in each line. Rates of switching were then
      determined after fly transmission of the first line and generated per capita rate
      values of greater than 2 x 10(-3) in three of four populations examined. In the
      fourth population the switch rate was lower: less than 7 x 10(-5) switches/
      cell/generation. These data show that rates of antigenic variation are several
      orders of magnitude lower in syringe-passaged lines, such as those routinely used
      in the majority of laboratory studies, compared with most recently fly
      transmitted lines. They also show that the reduction in switching rate associated
      with syringe passaging is reversible and is thus unlikely to be caused by
      mutation.

PMID- 9252593
TI  - Optimisation of the BgaB reporter system: determination of transcriptional
      regulation of stress responsive genes in Bacillus subtilis.
AB  - We constructed and characterised a new system to determine transcriptional
      regulation of genes in Bacillus subtilis. The system is based on the B.
      stearothermophilus-derived beta-galactosidase BgaB. In contrast to the systems
      described up to now the BgaB protein is not degraded in response to environmental
      stresses. We optimised buffer conditions for BgaB assays and developed a protocol
      which allows measurement of BgaB activity without background problems. To test
      the system we determined induction of the B. subtilis clpC gene in response to
      stress. Induction of this gene in response to stress occurred as described.

PMID- 9252595
TI  - A longitudinal, statistical study of reoperation rates in craniosynostosis.
AB  - A prospective, statistical study of reoperation rates was done in the treatment
      of 167 consecutive children with nonsyndromic and syndromic craniosynostosis over
      a 6-year period at Scottish Rite Children's Medical Center in Atlanta, Georgia.
      Mean length of follow-up was 2.8 years, with a range of 3 months to 6 years.
      Reoperation equal to or exceeding the magnitude of the original procedure
      occurred in 7 percent of cases. Multiple regression analysis revealed several
      factors associated with reoperation: Females and children with syndromic
      synostoses were more likely to require reoperation. Total reoperation rates for
      syndromic and nonsyndromic synostoses were 27.3 and 5.9 percent, respectively.
      Age at initial surgery, length of operation, and estimated blood loss did not
      predict a higher reoperation rate.

PMID- 9252594
TI  - Transplantation of chondrocytes utilizing a polymer-cell construct to produce
      tissue-engineered cartilage in the shape of a human ear.
AB  - This study evaluates the feasibility of growing tissue-engineered cartilage in
      the shape of a human ear using chondrocytes seeded onto a synthetic biodegradable
      polymer fashioned in the shape of a 3-year-old child's auricle. A polymer
      template was formed in the shape of a human auricle using a nonwoven mesh of
      polyglycolic acid molded after being immersed in a 1% solution of polylactic
      acid. Each polyglycolic acid-polylactic acid template was seeded with
      chondrocytes isolated from bovine articular cartilage and then implanted into
      subcutaneous pockets on the dorsa of 10 athymic mice. The three-dimensional
      structure was well maintained after removal of an external stent that had been
      applied for 4 weeks. Specimens harvested 12 weeks after implantation and
      subjected to gross morphologic and histologic analysis demonstrated new cartilage
      formation. The overall geometry of the experimental specimens closely resembled
      the complex structure of the child's auricle. These findings demonstrate that
      polyglycolic acid-polylactic acid constructs can be fabricated in a very
      intricate configuration and seeded with chondrocytes to generate new cartilage
      that would be useful in plastic and reconstructive surgery.

PMID- 9252596
TI  - Distraction osteogenesis of costochondral neomandibles: a clinical experience.
AB  - Distraction osteogenesis quickly has become a mainstay in the treatment of
      craniofacial syndromes with mandibular hypoplasia. We report on a series of eight
      patients undergoing distraction osteogenesis of neomandibles constructed with
      costochondral grafts. The length of distraction, resting phase between
      distraction and device removal, and complication rate were significantly greater
      in the rib-graft distraction group when compared with our series of native
      mandibular distraction patients (n = 21 devices). Most complications were minor,
      including pintrack infection and hardware failure; however, major complications
      included fibrous union and facial nerve praxia. Secondary procedures have been
      able to be performed successfully on previously distracted rib grafts as well.

PMID- 9252597
TI  - Surgical approach to midline skull base tumors with olfactory preservation.
AB  - Through the frontal approach, a skull base tumor in the deep midline region is
      obscured by the cribriform plate. This paper demonstrates our experience of
      operating on seven patients with midline skull base tumors posterior to the
      cribriform plate using a technique of maintaining the olfactory-cribriform
      anatomy. Following a bifrontal craniotomy and an orbitonaso-glabellar osteotomy,
      a circumferential osteotomy of the cribriform plate and horizontal incision of
      the nasal mucosa permitted mobilization of the cribriform plate unit along with
      the frontal lobe, providing a wide exposure of the posterior midline area. Tumors
      were resected from the posterior nasopharynx, ethmoid sinus, sphenoid sinus, and
      upper portion of the clivus. The skull base defects were repaired with the
      bipedicled temporoparietal galeal flap. Two patients lost olfaction because of
      poor preservation of the nasal mucosa and intradural dissection of the olfactory
      bulb. Five patients showed complete recovery of olfaction in 8 weeks. None of the
      patients developed cerebrospinal fluid leakage, infection, or increased
      neurologic deficits. En bloc mobilization of the cribriform plate and the
      bipedicled temporoparietal galeal flap are very useful for the management of
      midline cranial base tumors posterior to the cribriform plate as long as the
      olfactory unit is not involved with tumors.

PMID- 9252598
TI  - Massive abdominal-wall hernia reconstruction with expanded external/internal
      oblique and transversalis musculofascia.
AB  - We describe a technique for expansion and primary closure of massive and large
      recalcitrant abdominal-wall hernias in the middle and lower abdomen utilizing
      expanders placed in the lateral abdominal wall between the external oblique and
      the deeper complex of the internal oblique and transversalis fasciae. Since this
      technique describes expansion of the lateral abdominal wall, insertion incisions
      are made in the lateral abdominal wall away from the primary zone of injury
      surrounding the abdominal hernia and without interrupting the blood supply or
      innervation to the abdominal-wall muscle, fascia, or skin. This technique,
      described in four patients with massive abdominal-wall hernias, has been used
      successfully for primary closure with vascularized autogenous abdominal-wall
      fascia, obviating the need for interposition of prosthetic material or
      extraabdominal flaps.

PMID- 9252599
TI  - Paget's disease of the groin: report of seven cases.
AB  - Only 27 cases of Paget's disease of the groin have been reported to the present.
      Our aim was to describe the clinical behavior and treatment of this disease. A
      retrospective analysis of patients seen at the Mayo Clinic over a period of 25
      years (January of 1970 to December of 1995) was undertaken. We included patients
      with lesions of the groin (isolated or associated with penile/scrotal locations)
      and with histologic confirmation of the diagnosis. We found seven patients, all
      male; three patients had isolated lesions. Their mean (SD) age was 73 (8.3)
      years. Special stains and immunohistochemistry confirmed the diagnosis in all
      patients. A wide local excision was performed in every patient. Three patients
      had recurrence; one of them died with multiple pulmonary metastases 4 years
      later. Two patients presented with history of associated malignancy (prostatic
      and renal cell carcinoma). Paget's disease of the groin is extremely infrequent.
      Its origin seems not to be a simple extension from the genital area. Most
      diagnoses can be made by light microscopy. Wide local excision with free margins
      is the treatment of choice. Local recurrence occurs in half of patients with
      tumor-free margins by frozen section; long-term follow-up is warranted. Distant
      metastases occur rarely, although they can be fatal.

PMID- 9252600
TI  - Unilateral multilayered musculocutaneous V-Y advancement flap for the treatment
      of pressure sore.
AB  - We have devised a modified technique using the gluteus maximus musculocutaneous
      flap as multilayered sliding V-Y advancement to cover pressure sores on the
      sacral area. Nine patients with relatively large (average 7 x 7 cm) sacral grade
      IV pressure sores underwent unilateral multilayered V-Y advancement flap. All
      patients were followed for a minimum of 8 weeks. The mean postoperative follow-up
      was 32.3 months, with a range of 24 to 39 months. Using this technique, the
      success of surgery, i.e., the percentage of sores that healed, was 100 percent in
      our patients. The advantages of this technique include sufficient advancement of
      the flap, coverage of large ulcer defects using only a unilateral
      musculocutaneous flap, and preservation of the contralateral gluteus maximus
      muscle for future use.

PMID- 9252601
TI  - Reducing the period of immobilization following pressure sore surgery: a
      prospective, randomized trial.
AB  - The cost to care for a patient with pressure sores can be exorbitant. One part of
      this expense results from the prolonged postoperative immobilization. Published
      protocols report 3 to 8 weeks of immobilization; however, there are no studies
      that establish longer periods to be superior. To justify our 3-week protocol, we
      conducted a prospective, randomized trial of 2 versus 3 weeks of postoperative
      immobilization. Each patient was randomized preoperatively to either 2 or 3 weeks
      of postoperative immobilization. A total of 42 patients with a diagnosis of
      paraplegia, tetraplegia, or multiple sclerosis and a solitary pressure sore were
      enrolled over 5 years. The complication rates in the two groups (9 of 23, or 39
      percent, for the 2-week group and 9 of 19, or 47 percent, for the 3-week group)
      were not statistically different (p < 0.493). However, the time to mobilization
      was significantly reduced in the 2-week group (16.1 +/- 6.1 versus 22.9 +/- 4.9
      days, p < 0.0003), as was the time to achieve sitting (21.2 versus 28.9 days, p <
      0.0026). In summary, 2 weeks of postoperative immobilization following surgery is
      adequate for uncomplicated solitary pressure sores.

PMID- 9252602
TI  - 1457 years of microsurgical experience.
AB  - Microsurgery is a relatively new field of surgery involving various methods and
      practices that are currently evolving. Our goal was to register the current
      practices employed by the members of the American Society for Reconstructive
      Microsurgery. A survey was mailed to the 319 members of the society, resulting in
      a response rate of 33 percent (106 of 319). The data reflect the combined
      experience of 10,839 free-tissue transfers and 3487 digital and upper and lower
      extremity replants over a 4-year period between 1990 and 1994. Practices
      employed, such as pharmacologic adjuvant therapy, monitoring techniques, flap
      types, and success rates reported by the members of the American Society for
      Reconstructive Microsurgery, were analyzed.

PMID- 9252603
TI  - Significance of elbow extension in reconstruction of prehension with reinnervated
      free-muscle transfer following complete brachial plexus avulsion.
AB  - Thirty-one patients with complete avulsion of the brachial plexus underwent
      reconstruction of elbow extension by intercostal nerve transfer following
      reconstruction of prehension with either a single or double free-muscle transfer.
      Long-term results of elbow extension were evaluated in 24 patients. Reinnervation
      of the triceps muscle took longer than that of the transferred muscle on serial
      electromyographic examinations, and the eventual strength of the triceps muscle
      was weak. None attained M5 grade, 2 achieved M4 grade, 4 achieved M3 grade, 8
      achieved M2 grade, 5 achieved M1 grade, and another 5 achieved M0 grade. However,
      despite the weak recovery, 14 patients were able to obtain useful functional
      recovery of the triceps muscle, enabling it to stabilize the elbow joint against
      the transferred muscle, which acted as simultaneous elbow flexor and wrist or
      finger extensor. Elbow stability is imperative in order to obtain voluntary
      finger function following free-muscle transfer. Should the triceps muscle fail to
      recover following intercostal nerves neurotization, transferring the reinnervated
      infraspinatus to the triceps is an optional procedure to provide stabilization of
      the elbow.

PMID- 9252604
TI  - Peripheral nerve regeneration: the effects of postoperative irradiation.
AB  - The purpose of this study was to evaluate the effects of postoperative external
      cobalt-60 beam irradiation on nerve regeneration. Sixty-five 250-gm male Sprague
      Dawley rats were studied. Peripheral nerve regeneration was measured by walking
      track analysis and histomorphology of the proximal, graft, and distal nerve
      segments. These 65 animals underwent a 1.5-cm interpositional nerve graft into
      the right posterior tibial nerve. The left leg served as a control. Each animal
      was then randomly allocated into one of four groups. Group 1 served as control.
      Groups 2 through 4 were subjected to external cobalt-60 gamma-ray irradiation
      through a 2.5-cm circular portal for a total fractionated dose of 30, 50, and 70
      Gy beginning on postoperative day 3. Radiation was administered in 2-Gy
      fractions, 5 fractions per week, with a top-up dose of 16 Gy given at the end of
      the fractionated irradiation. Walking track analysis was performed at 30, 60, 90,
      and 120 days after nerve grafting. At the conclusion of 120 days, sections of the
      proximal, grafted, and distal nerve were harvested, stained, and examined
      histomorphologically. Hematoxylin and eosin stains also were obtained. Evaluation
      of the print-length index demonstrated no statistical difference between the
      unirradiated controls and the irradiated groups. The total number of axons per
      square millimeter and nerve fiber density per square millimeter were
      significantly decreased in the distal segment of all the irradiated groups when
      compared with controls. Despite the reduction in myelinated regenerating fibers,
      no reduction in function was observed, as measured by walking track analysis. We
      would therefore recommend immediate reconstruction of peripheral nerve defects in
      the face of postoperative irradiation.

PMID- 9252605
TI  - Three-dimensional reconstruction of cutaneous arteries of the back by computer
      graphic imaging.
AB  - Computer graphics using a personal computer were introduced to demonstrate the
      three-dimensional architecture of cutaneous arteries of the back in humans: the
      direct cutaneous artery of the circumflex scapular artery and the perforating
      cutaneous branches and musculocutaneous perforators of the superficial cervical,
      posterior intercostal, and thoracodorsal arteries. The entire thickness of the
      skin and underlying subcutaneous tissue over the deep fascia was obtained from
      five fresh cadavers injected systemically with lead oxide-gelatin mixture, and
      the integument was divided into the three layers; the skin, superficial
      adipofascial layer with the superficial fascia, and the deep adipofascial layer.
      Computer graphic reconstruction of the cutaneous arteries was performed using
      data based on angiograms of the three layers. The computer graphic depictions
      demonstrated in which layer cutaneous arteries branched and how the vessels were
      running in each layer by displaying each layer in different colors: red, yellow,
      and blue. Knowledge of the three-dimensional structure and architecture of the
      cutaneous arteries will aid in the development of flaps that use a portion of the
      skin and subcutaneous adipofascial tissue.

PMID- 9252606
TI  - Elevated levels of testosterone receptors in keloid tissue: an experimental
      investigation.
AB  - Testosterone-binding receptor protein analyses were performed in keloids of 24
      patients. According to their clinical appearance (hyperemia, pain, rapid growth,
      etc.), the lesions were subdivided into regions of minor and major clinical
      keloid activity. Biopsies were taken from active and inactive parts of the
      keloids, respectively, as well as from normal adjacent skin. The mean receptor
      amount in femtomoles per milligrams of tissue was 0.046 for active (SD = 0.037),
      0.038 for inactive keloidal lesions (SD = 0.032), and 0.012 for normal skin. The
      corresponding receptor amount per microgram of DNA was 3.356 fmol (SD = 2.171)
      for active, 2.077 fmol (SD = 1.427) for inactive keloidal, and 1.010 fmol (SD =
      1.190) for normal tissue. Statistical evaluation was performed using a two-way
      analysis of variance, with the two factors being individual subject and type of
      tissue. When differences were found, then Tukey's comparison was done to assess
      where those differences were. Comparisons of the receptor amount per milligram of
      tissue significant at the 0.05 level revealed significant differences between
      active keloid tissue and normal skin tissue and inactive and normal tissue (p <
      0.01) respectively, while different receptor amount per microgram of DNA was
      significant between active and inactive and active and normal tissue (p < 0.01).
      These data suggest that elevated androgen receptor levels exist in clinical
      active keloid tissue and that possible therapeutic means might include topical
      antiandrogen therapy.

PMID- 9252607
TI  - The use of quantitative bacteriologic assessment of bone.
AB  - The purpose of this paper was to examine whether quantitative bacteriologic
      assessment of bone is a reliable indicator of the adequacy of debridement of
      draining wounds involving bone. This is a retrospective review of 31 consecutive
      patients treated for draining posttraumatic/ surgical wounds involving bone.
      Nineteen patients met the necessary criteria and were included in the study.
      These patients underwent radical debridement of bone and soft tissue,
      intraoperative assessment of the debrided wound by rapid slide quantitative
      bacteriologic assessment, and closure with well-vascularized tissue. Clinical
      assessment of vascularity and rapid slide quantitative bacteriologic assessment
      of cancellous bone and soft tissue were the only prerequisites used in
      determining the appropriateness of wound closure in this study. At the time of
      most recent follow-up, none of the 19 patients had recurrent wound drainage. Two
      patients required a second procedure to partially elevate their flaps and drain
      recurrent soft-tissue infections. None of the patients had recurrence of bony
      infection. Seventeen patients who presented initially with fractures or
      osteotomies all had successful bone unions. This study demonstrates that the
      technique of rapid slide quantitative bacteriologic assessment of cancellous bone
      is a useful adjunct to surgical judgment and allows one to close draining wounds
      (frequently with complex wound closure options) with a high level of confidence.

PMID- 9252608
TI  - Functional urinary bladder wall substitute using a free innervated latissimus
      dorsi muscle flap.
AB  - This study was designed to investigate the ability of the latissimus dorsi muscle
      in situ to evacuate a bladder reservoir and to study the functional, anatomic,
      and histopathologic results of partial or subtotal bladder reconstruction with an
      innervated free latissimus dorsi muscle in mongrel dogs. In group I (four dogs),
      the latissimus dorsi muscle was dissected and tailored in situ. Then the so
      formed pedicled latissimus dorsi muscle flap was wrapped around tissue expanders
      of varying sizes (volumes of 50, 100, and 150 cc, respectively) to form a bladder
      like reservoir. Electromyography and intraluminal pressure measurements were done
      at the time of surgery and 6 months thereafter using a standard electromyograph
      and a Dantec urodynamic unit. In group II (four dogs), the dome of the bladder
      wall was removed, with up to 50 percent of the mucosal layer being left intact.
      The resulting muscular defect was repaired with a free innervated latissimus
      dorsi muscle flap. The transferred latissimus dorsi muscle was shaped and wrapped
      around the bladder in a spiral form, with particular attention to the resting
      tension. The thoracodorsal vessels were anastomosed to the pelvic branches of the
      hypogastric vessels, and the thoracodorsal nerve was coapted to a pelvic motor
      nerve that was selected by use of a nerve stimulator. Cystography and urodynamic
      studies were performed after 3, 6, and 9 months. Electromyography was done after
      9 months, before sacrifice of the animals, which was followed by regular
      histologic and electron microscopic examinations. Stimulation of the
      thoracodorsal nerve of the reconfigured latissimus dorsi muscle reservoirs in
      situ after 6 months yielded average intraluminal pressures of 190 cmH2O at
      maximum capacity and 35 cmH2O at a minimum capacity of 10 to 15 cc. Stimulation
      of the latissimus dorsi muscle transferred to the bladder resulted in a visible
      and measurable contraction of the transplanted muscle after 9 months. Urodynamic
      values preoperatively and postoperatively were basically unchanged. During
      cystography, the bladder outline was smooth during both filling and voiding.
      Light and electron microscopic examinations confirmed viable, reinnervated
      muscle. The reconfigured pedicled latissimus dorsi muscle has the ability to
      evacuate a bladder-like reservoir after nerve stimulation. A detrusor function of
      the bladder can be induced through the contractility of a reinnervated free
      latissimus dorsi muscle that was wrapped around the bladder. An innervated free
      latissimus dorsi muscle flap does not undergo severe muscle fibrosis,
      contracture, and atrophy such as occur after transfer of completely or partially
      denervated, pedicled muscle. This means that a functional bladder
      reconstruction/augmentation can be achieved by microneurovascular transfer of a
      latissimus dorsi muscle flap.

PMID- 9252609
TI  - Pelvic ring reconstruction with a vascularized bone flap of femur.
AB  - We have used a vascularized bone flap of femur for pelvic ring reconstruction
      after tumor resection in which amputation of the lower extremity was required.
      The vascularized femoral graft is an alternative technique in restoration of
      pelvic ring continuity with vascularized bone autografts.

PMID- 9252610
TI  - Triplicated thumb.
AB  - A polydactyly anomaly of the thumb with three nails, two metacarpals, and seven
      phalanges is presented. This anomaly is named triplicated thumb, and its place in
      Wassel's classification is discussed. The patient was treated according to the
      principles of surgery of polydactyly anomalies. Good motor function with
      acceptable aesthetic appearance was obtained.

PMID- 9252611
TI  - Reconstruction of defects of the entire vermilion with a buccal musculomucosal
      flap following resection of malignant tumors of the lower lip.
AB  - We reconstructed a defect of nearly the entire lower vermilion using a buccal
      musculomucosal flap following resection of a malignant tumor of the lower lip and
      obtained satisfactory results. The buccal musculomucosal flap was semi-spindle
      shaped and pedicled at the angle of the mouth. A flap measuring as much as 1.5 cm
      in width and 5 cm in length could be raised while ensuring that fibers of the
      buccinator muscle extended over its entire length. Using this technique, it was
      possible to reconstruct a wide defect following tumor resection and removal of
      almost the entire lower vermilion by means of only a transposition of a
      unilateral buccal musculomucosal flap after about one-quarter of the lower lip
      had been excised and sutured primarily. Reconstruction with this technique is a
      two-stage operation, and a secondary minor touch-up operation is performed on the
      angle of the mouth at the same time as repair of the dog-ear of the pedicle.
      Advantages of this technique are that food can be taken orally soon after the
      operation, hemodynamics in the flap are maintained stably because the flap
      contains fibers of the buccinator muscle, and the vermilion is given a natural
      eminence. In addition, postoperative drooling is minimized, and sensation returns
      to the vermilion within the early postoperative period. Based on these
      advantages, we think our technique should be the first choice for carrying out
      reconstruction of defects that are located mainly in the lower lip vermilion
      because this is a safe and reliable method with which we performed 12 cases of
      vermilion reconstruction without flap necrosis and with satisfactory aesthetic
      and functional results.

PMID- 9252612
TI  - Nipple-areola reconstruction with a dermal-fat flap and rolled auricular
      cartilage.
AB  - In reconstruction of the nipple-aerola complex, it is important to maintain
      nipple projection. The conventional methods of reconstructing the nipple using
      local skin flaps maintain the feature for a certain period postoperatively, but
      the height of the nipple eventually flattens as the scars soften over time.
      Considering that sustaining the feature of the nipple is most important for
      achieving and maintaining nipple projection, we have therefore devised a new
      operative technique. Rolled auricular cartilage is placed in the center of the
      bridge of the dermal base and is wrapped with bilobed dermal-fat flaps. This
      technique has the following advantages: The cartilage produces and sustains a
      good form of the feature without subcutaneous depression because the cartilage is
      supported by the bridge of the dermal base. Since the dermal base forms a bridge,
      the method is safe, maintains good circulation, and does not lead to any necrosis
      in the flap. This method also was compared with a method in which the rolled
      auricular cartilage is wrapped with a trilobed dermal fat flap.

PMID- 9252613
TI  - The rectus abdominis myocutaneous flap combined with vascularized costal
      cartilages in reconstructive craniofacial surgery.
AB  - The efficacy of osteocutaneous or vascularized bone flaps for reconstruction of
      massive skeletal and soft-tissue defects has been supported by recent
      descriptions in the literature. In this article we presented an alternative
      technique, which is the rectus abdominis myocutaneous flap combined with
      vascularized eighth and ninth costal cartilages, for reconstruction of midfacial
      composite defects. The vascular pedicle of the composite flap is the deep
      inferior epigastric artery and vein. The costal cartilages are supplied by the
      perichondrial vascular network through the anterior intercostal vessels
      connecting with the deep epigastric vascular system. Vascularized costal
      cartilages are considered to reduce the incidence of postoperative complications
      and resorption of this material. This technique is a useful tool for restoration
      of craniofacial contour in reconstructive head and neck surgery.

PMID- 9252614
TI  - A simple, inexpensive method for precise application of cyanoacrylate tissue
      adhesive.
AB  - The use of cyanoacrylate tissue adhesives is well described in the literature for
      closure of skin wounds. The main problem with their application in my hands is
      that the glue tends to flow/run away from the point of application, making
      precise application difficult even when the supplied plastic tube is used. This
      problem is inherent to the low viscosity of the adhesive. I hereby describe a
      simple, inexpensive technique whereby a "blue" needle is fitted to the tip of the
      Histoacryl tube and used to apply the adhesive in a precise, fine, and
      predictable manner to the specific area or point required, reducing any "running"
      of the glue to undesired adjacent areas. A fast, simple, and elegant way of
      insetting a skin graft using cyanoacrylate glue is also described.

PMID- 9252615
TI  - A new dressing design for use with maggot therapy.
AB  - Maggot therapy has been used since the 1930s for treating soft-tissue wounds.
      Despite decades of experience with this therapy, selecting appropriate dressing
      materials continues to be a problem. Before initiating our maggot therapy
      service, we needed to develop a dressing that would (1) prevent the maggots from
      escaping, (2) permit oxygen to reach the maggots, (3) facilitate drainage, (4)
      allow inspection of the wound, (5) require minimal maintenance, and (6) be of low
      cost. The optimal dressing design proved to be a two-layered cagelike dressing,
      the bottom layer of which comprised a hydrocolloid pad, applied to the
      surrounding healthy skin and covered by a fine chiffon or nylon mesh. Liquefied
      necrotic tissue drained through the mesh and was absorbed in a top layer of
      gauze, which was replaced periodically. Thus it was possible to contain the
      maggots within the wound by means of readily available materials.

PMID- 9252616
TI  - Ear projection and the posterior auricular muscle insertion.
AB  - Prominent ears is a common congenital anomaly affecting approximately 5 percent
      of the general population. The etiology has been attributed to three basic
      deformities in the ear structure: valgus of the concha with a cranioauricular
      angle greater than 40 degrees, underfolding of the anthelix, and rarely,
      hypertrophy of the concha. It is believed that by virtue of its insertion onto
      the ponticulus, the cranial surface of the concha, the posterior auricular muscle
      may function to pull the auricle back toward the head. A proximally
      (anteromedially) displaced insertion site would decrease the length of the
      effective momentum of the muscle, leading to protrusion of the auricle. This
      study was conducted to determine if indeed a relationship between the posterior
      muscle insertion site and ear projection could be established clinically by
      measuring these parameters intraoperatively in patients presenting for otoplasty
      and in patients without prominent ears who required conchal cartilage grafts for
      other procedures.

PMID- 9252618
TI  - Anthropomorphic breast measurement: protocol and results in 50 women with
      aesthetically perfect breasts and clinical application.
AB  - This paper presents a simple protocol for the measurement and evaluation of the
      difficult physiognomy of the female breast and the application of the protocol in
      clinical practice. The protocol includes measurement of the breast and its
      landmarks and their relevant position from fixed skeletal points. Volume was
      measured with the Grossman-Roudner device. The protocol provides a useful tool in
      the accurate evaluation of patients preoperatively and in the assessment of
      surgical results. The protocol is compared with the two previously reported
      protocols. The paper presents the anthropomorphic measurements of 50 women with
      aesthetically perfect breasts utilizing this protocol. Aesthetically perfect was
      defined as a nonptotic breast in which no common aesthetic procedure would be
      considered appropriate (excluding augmentation) to enhance the breast's form.
      Results were compared with those reported in the two previous studies. The paper
      presents the clinical correlation obtained by statistical analysis of the results
      of the measurements of the 50 women. Although the results of the measurements
      indicate the range and variance in the aesthetically perfect breast, there still
      was a statistically significant correlation of some of the parameters of the
      breast and torso shape to breast volume. This correlation can be used
      preoperatively to predict desired breast shape and volume in breast augmentation,
      reduction, and reconstruction. Clinical application of the concepts proposed will
      lead to better surgical goal orientation and improve evaluation of surgical
      results. A formula for calculating appropriate breast size based on torso
      parameters is presented.

PMID- 9252617
TI  - Reduction malarplasty.
AB  - One of the most frequently requested facial contour improvement procedures in the
      Orient is reduction malarplasty. However, until recently, osteotomies in the
      malar region have been performed by means of a coronal incision that required a
      larger incision and more invasive procedure than many patients are comfortable
      with when considering an elective cosmetic surgical procedure. We have developed
      a reduction malarplasty method to improve facial contours that circumvents the
      drawbacks inherent in the conventional method. In our method, the protrusion in
      the cheekbone area is corrected by performing an osteotomy of the zygoma through
      an intraoral incision and an osteotomy of the zygomatic arch through a small
      preauricular incision.

PMID- 9252619
TI  - The arterial supply of the face lift flap.
AB  - The cutaneous arterial circulation of the face lift flap was investigated using
      multiple anatomic techniques in fresh cadaver specimens. Perforation sites of the
      transverse facial and submental arteries were preserved or transected according
      to protocol during bilateral rhytidectomy prior to selective injections with ink
      or lead oxide. It was observed that the transverse facial perforating artery
      provides the major direct blood supply to the lateral cheek and preauricular area
      following rhytidectomy if preserved. This perforator occupies a constant anatomic
      location 3.1 cm lateral and 3.7 cm inferior to the lateral canthus with 95
      percent tolerance limits of +/-1.1 cm. There is greater variability in localizing
      the submental perforating artery; however, this perforator also contributes
      significantly to lateral facial blood supply. Both perforator locations are
      within the area of "standard" undermining for rhytidectomy; however, they may be
      preserved during this procedure if desired. Transection of the lateral facial
      perforators leaves vascularization of these cutaneous areas dependent on
      collateral flow from the pedicle of the face lift flap. The ability to preserve
      optimal blood supply to the lateral face lift flap may be useful in the clinical
      setting of a vascularly compromised or smoking patient.

PMID- 9252621
TI  - Face lift: which technique?

PMID- 9252620
TI  - The effect of chemosurgical peels and dermabrasion on dermal elastic tissue.
AB  - Chemosurgical peel is a technique that has been used widely by plastic surgeons
      and dermatologists to remove fine and deep wrinkles of the skin. However, the
      reaction of elastic tissue to the cutaneous application of commonly used chemical
      peeling agents has not been defined. This study comparatively assessed the
      alteration in dermal histology and mechanical properties of skin following
      treatment with 25% and 50% trichloroacetic acid, Baker's phenol solution, and
      dermabrasion. Yucatan minipigs served as the animal model. The skin was analyzed
      at five intervals over 6 months after treatment using histologic, quantitative,
      and mechanical analysis (hematoxylin and eosin, elastic tissue, and Sirius red
      stains, computerized digital morphometry, and a tensiometer). At 6 months we
      found no change in the quality, structure, or arrangement of elastic fibers in
      skin treated with a single application of 25% and 50% trichloroacetic acid or
      dermabrasion when compared with untreated skin. Skin treated with Baker's phenol
      solution showed a marked morphologic change in the elastic fibers. The fibers
      within the regenerated zone of dermis were sparse, wispy, and immature at 6
      months after treatment. Preliminary tensiometric analysis of phenol-treated skin
      at 6 months indicated that the skin was stiffer and weaker. This study questions
      the possibility of long-term change to the skin by the deep penetration of
      caustic chemicals to remove wrinkles and rejuvenate the skin.

PMID- 9252622
TI  - Personal technique of face lifting.

PMID- 9252623
TI  - Lateral SMASectomy.

PMID- 9252624
TI  - Face lift.

PMID- 9252625
TI  - Mucous cyst--a postrhinoplasty complication: outcome and prevention.
AB  - We present three cases of mucous cyst as a rare postrhinoplasty complication that
      were seen in our clinic during the last 16 years. They were located in three
      different positions of the nose: bony and cartilaginous part of the dorsum of the
      nose as well as over the alar cartilage part of the nose. We were able to treat
      all three patients successfully by excision of the cyst through intranasal or
      open approaches. In reviewing the literature and from our own experience we come
      to the conclusion that postoperative clearing of all tissue remnants, especially
      mucous parts, and a careful, atraumatic operation by forming an intact
      mucoperichondrial tube for intransal osteotomy as well as for hump removal are
      the best prevention of postrhinoplasty complications such as mucous cysts.

PMID- 9252626
TI  - Unusual masses found within ruptured silicone gel breast prostheses.
AB  - Imaging of breast implants has assumed more importance in medicine than ever
      before. Radiologists and surgeons alike have struggled to accurately identify
      folds in prostheses, rupture of prostheses, and migration of gel. Here we present
      two patients with an unusual presentation of masses within the gel of ruptured
      silicone gel-containing prostheses. In one instance, the mass was an organized
      hematoma. In the other, two round, calcified masses were found that we presume
      are hematomas that have become calcified over time. Radiologists and surgeons
      identifying spherical or ovoid masses seemingly within gel breast prostheses
      should entertain the possibility that the mass represents an organized hematoma
      and that the implant is ruptured.

PMID- 9252627
TI  - Retractor with mobile endoscope.
AB  - I have designed two retractors with mobile endoscopes that allow an assistant to
      lift up the flap and the endoscope. By doing this, the assistant maintains the
      optical cavity open while the surgeon dissects. There are two models, one with
      180-degree lateral swing and the other with motion in all directions (vertical
      and lateral).

PMID- 9252628
TI  - Apert syndrome, not Apert's syndrome: Apert neither had nor owned the syndrome
      that bears his name.

PMID- 9252629
TI  - Is there any medicine in the house?

PMID- 9252630
TI  - Anxiety disorders in plastic surgery.
AB  - Surgery is a stressful event, with the potential for profound disturbance to the
      patient's psychological and physiologic homeostasis. Cosmetic surgery is a
      particularly intense psychological experience because, in addition to the usual
      concerns about surgical side effects, cosmetic patients bring their hopes and
      expectations for improved self-image, putting them at risk for the added anxiety
      of disappointment. High levels of anxiety coupled with the perception of
      vulnerability or threat to self can cause significant psychological reactions
      complicating care for the plastic surgical patient. This paper outlines the
      diagnostic features of the common types of anxiety disorders seen in plastic
      surgical patients, and it offers treatment strategies for the practitioner,
      delineating when referral to a mental health expert is advised. Specific clinical
      case studies of panic attack, posttraumatic stress disorder, and acute stress
      disorder are presented to illustrate the variety of abnormal anxiety responses
      that may be encountered in the perioperative setting. Interventions for the
      anxious patient are part science and part art. Careful questioning and
      psychosocial assessment can identify those patients who are at greater risk for
      psychological problems after surgery. However, some patients may mask or keep
      secret their concerns, which can be manifested with resulting anger and
      hostility. Plastic surgeons must use appropriate indicators of psychological
      anxiety and measure a specific patient's reactions to surgery to make the
      diagnosis of abnormal anxiety. Close follow-up by the plastic surgical team is an
      essential part of the anxiety disorder patient's psychological treatment, but it
      is imperative that these problematic patients be referred promptly to a qualified
      mental health professional to limit their adverse experience and promote their
      well-being. Patients who are less anxious during the perioperative period report
      less emotional distress and fewer defensive behaviors and are likely to be more
      satisfied with the outcome of their surgery.

PMID- 9252631
TI  - Preoperative psychological evaluation and intervention in prospective amputees.

PMID- 9252632
TI  - Laparoscopically assisted colocolpopoiesis.

PMID- 9252633
TI  - Heating pad burn of a reconstructed breast.

PMID- 9252634
TI  - Clonidine as premedication for rhinoplasty.

PMID- 9252635
TI  - Donor-site morbidity of reversed radial artery forearm flaps.

PMID- 9252636
TI  - Knee radiographs in Pfeiffer and Crouzon syndromes.

PMID- 9252637
TI  - A classic surgical method for the treatment of axillary osmidrosis.

PMID- 9252638
TI  - Abdominal hernias after breast reconstruction.

PMID- 9252639
TI  - Steroids with face lift.

PMID- 9252640
TI  - The effect of ketorolac on clotting.

PMID- 9252641
TI  - Superficial liposculpture of the face and neck.

PMID- 9252642
TI  - Labial incompetence: a marker for progressive bone resorption in Silastic chin
      augmentation.

PMID- 9252643
TI  - Anaplastic T-cell lymphoma in proximity to a saline-filled breast implant.

PMID- 9252644
TI  - Breast implants.

PMID- 9252645
TI  - The Ras farnesylation inhibitor BZA-5B increases the resistance to cisplatin in a
      human melanoma cell line.
AB  - Ras proteins have been implicated in transducing cellular responses to DNA
      damaging agents. We used BZA-5B, an inhibitor of Ras-farnesylation, to examine
      the role of Ras in cellular sensitivity to cisplatin. A human melanoma cell line
      (224) with a Gln61Arg mutation in N-ras was used for these studies. We report
      that BZA-5B treated cells show an increased resistance to cisplatin. BZA-5B
      treatment decreased the number of cells showing in situ DNA fragmentation and
      increased cell viability and clonogenic survival after cisplatin treatment.
      Further experiments showed that cisplatin induction of the immediate early genes
      c-jun and p21cip1 was not affected by BZA-5B. Finally, we show that cisplatin
      causes only weak activation of Jun N-terminal kinase (JNK) in a human melanoma
      cell line. We conclude that inhibition of Ras function decreases the sensitivity
      of human melanoma cells to cisplatin-induced cell death.

PMID- 9252646
TI  - Increased thymidine kinase and thymidylate synthase activities in human
      epithelial ovarian carcinoma.
AB  - BACKGROUND: Thymidylate synthase (dTMP synthase, EC 2.1.1.45) is responsible for
      the de novo biosynthesis of thymidylate (dTMP) whereas thymidine kinase (TdR
      kinase, EC 2.7.1.21) is the salvage enzyme which leads to the production of dTMP
      even in presence of d TMP synthase inhibition. The current study was undertaken
      to compare the steady-state activities of d TMP synthase and TdR kinase in
      extracts of human epithelial ovarian carcinoma and normal ovaries. MATERIAL AND
      METHODS: Tissue extracts of epithelial ovarian carcinomas and normal ovaries were
      analyzed for activities of d TMP synthase (by a method that measures released
      3H2O) and TdR kinase (by polyethyleneimine impregnated (PEI) cellulose plate
      radioassay), methods established in this laboratory. RESULTS: The dTMP synthase
      activity (mean +/- S.E.) in extracts of ovarian carcinomas (N = 11) was 0.198 +/-
      0.069 and in extracts of normal ovaries (N = 12) it was 0.025 +/- 0.0004
      nmol/hr/mg protein. By contrast, TdR kinase activity in extracts of ovarian
      carcinoma (N = 13) was 27.7 +/- 8.5 compared to 1.0 +/- 0.3 nmol/hr/mg protein in
      extracts of normal ovaries (N = 15). CONCLUSION: The observed 140-fold higher TdR
      kinase activity suggests that DNA synthesis may continue despite inhibition of
      dTMP synthase with current schedules of 5-fluorouracil (5-FU) and leucovorin. The
      addition of azidothymidine, a competitive inhibitor of TdR kinase, to 5-FU and
      leucovorin might be a rational biochemical strategy to employ in patients with
      refractory ovarian carcinoma.

PMID- 9252647
TI  - Induction of premature mitosis in cells blocked in S-phase: possibilities of its
      use in cancer therapy.
AB  - Oncogenesis leads to weak regulations of many cell cycle checkpoints. This could
      be useful for cancer therapy. To test this assumption, five human malignant cell
      lines were used to induce premature mitosis by overriding the S-phase control,
      which ultimately leads to cell death. Two cell lines showed a significantly high
      frequency of premature mitotic cells induced by okadaic acid; whereas the others
      did not. One cell line, although having a high cyclin B level in cells blocked in
      S-phase, failed to show premature mitosis. The cyclin B level in cells blocked in
      S-phase alone could not explain the differential behavior of the cell lines. It
      was observed that in addition, the activation of cdc25 in these cells could also
      play an important role in the induction of premature mitosis in such cells.

PMID- 9252648
TI  - Effect of 6-diazo-5-oxo-L-norleucine (DON) on human carcinoid tumor cell
      aggregates.
AB  - The induction of glutamine starvation has been suggested as a potential target
      for antitumoral treatment using inhibitors of amidotransferase, an enzyme which
      mediates the conversion of glutamate to glutamine. Using multicellular aggregates
      from tumor cell lines, the effect of treatment with a suggested glutamine
      antagonist, 6-diazo-5-axo-L-norleucine (DON), was investigated. As indicators of
      treatment response, three different parameters were measured: aggregate size,
      uptake of 14C-methionine and secretion of Chromogranin A. Of six cell types
      evaluated (carcinoid, glioma, neuroblastoma pancreas and bladder cancer), the
      largest inhibition of 14Cmethionine uptake, amounting to 60%, was found in the
      carcinoid cell line BON. In this cell line the maximum effect was reached already
      at 10 microM concentration. DON induced marked growth inhibition in the BON
      aggregates which lasted 3-4 weeks after which regrowth started. During this
      period the secretion of chromogranin and methionine uptake was also inhibited.
      These studies suggest that the neuroendocrine cell line BON is especially
      vulnerable to treatment by DON and show that strong inhibitory effects are found
      at concentrations lower than that achieved in patient blood in previous clinical
      trials.

PMID- 9252650
TI  - Visualization of the metastatic process by green fluorescent protein expression.
AB  - We demonstrate here the visualization of the cancer metastatic process in live
      tissue in vivo by green fluorescent protein (GFP) expression. The human lung
      adenocarcinoma cell-line Anip 973 was transfected with the humanized GFP-S65T
      cDNA and stable high-level GFP-expressing transfectants were established. GFP
      transfectants were initially inoculated subcutaneously in nude mice. Five weeks
      after transplantation, when the tumor had reached 1.2 cm in diameter, fragments
      of subcutaneously tumor were implanted onto the visceral pleura of nude mice by
      surgical orthtopic implantation (SOI) as a spontenous metastatic model. GFP
      expressing cells were injected intravenously in nude mice as an experimental
      hematogenous metastasis model. Mice were sacrificed four and eight weeks after
      treatment. At eight weeks, SOI-treated mice had lymphogenous (3/4 mice) and
      direct seeding (3/4) metastasis in the pulmonary hilum, cervical lymph nodes, the
      mediastinum and contralateral pleural cavity as detected by GFP expression in
      live tissue. All intravenously injected mice had metastases in the lung (4/4) and
      some of them had metastases in the brain (2/4) and other organs (1/4) as detected
      by GFP expression in fresh tissue. Some of the lung metastases produced by
      intravenous injection remained as dormant small colonies even eight weeks after
      treatment. These different metastatic patterns after SOI and intravenous
      injection visualized by GFP expression indicates that initial steps of the
      metastatic cascade influence the subsequent progression of metastasis.

PMID- 9252649
TI  - Transient exposure to cytarabine increases peptide growth factor receptor
      expression and tumorigenicity of melanoma cells.
AB  - We have demonstrated that anticancer drugs at cytostatic concentrations enhance
      the expression and function of epidermal growth factor (EGF-R) and transferrin
      (TRF-R) receptors on human tumor cells. We hypothesized that these effects could
      represent a protective response of tumor cells to sublethal antiproliferative
      stimuli which could lead to enhanced growth potential. 72 hours exposure of human
      melanoma GLL-19 cells to 1,000 nM ara-C induced growth inhibition and increased
      the number of EGF-R, TRF-R and nerve growth factor receptor (NGF-R) on cell
      surface. Enhanced expression of beta 3 integrins CD49a, CD49c and CD49e, av
      integrin CD51, beta 3 integrin CD61, CD58/LFA3 and collagen IV and laminin was
      also detected in ara-C-treated GLL-19 cells. These changes at the tumor cell
      surface were paralleled by increased in vitro adhesion, invasive potential and
      clonogenic growth in soft agar and in vivo tumor formation. A more aggressive
      tumor cell phenotype is induced in human melanoma cells after transient exposure
      to cytostatic concentrations of ara-C.

PMID- 9252651
TI  - Induction of apoptotic cell death in three human osteosarcoma cell lines by a
      polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone)
      (MGBCP).
AB  - Our previous experiments have shown that methylglyoxal
      bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine synthesis inhibitor,
      suppresses the growth of osteosarcoma cells repressing their intracellular
      polyamine levels, and that this inhibition of cell growth is only partially
      reversed by the addition of polyamines. In the present study, we found evidence
      indicating that the incomplete recovery of cell growth by the addition of
      polyamines to the polyamine-depleted cells was due to programmed cell death
      (apoptosis) induced by MGBCP. Morphological changes showing blebbing and
      chromatin condensation were observed in MGBCP-treated cells, and hypodiploid
      subpopulations containing apoptotic cells were clearly visible in the profile of
      flow cytometric analysis. Characteristic oligonucleosomal-sized fragments were
      increased as the concentration of MGBCP was increased. The results presented here
      suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic
      cell death in three human osteosarcoma cell lines.

PMID- 9252652
TI  - Enhanced expression of cyclin-dependent kinase inhibitor in apoptosis of androgen
      independent prostatic cancer cell line induced by calcium ionophore.
AB  - In order to examine the relationship between apoptosis of androgen-independent
      prostatic cancer cells and cell cycle-associated proteins, TSU-pr1 human
      prostatic cancer cells were chronically exposed in vitro to the calcium ionophore
      ionomycin to sustain an elevation in their intracellular free calcium
      concentration. Temporal analysis demonstrated that the death of these cells does
      not require cell proliferation and involves fragmentation of genomic DNA into
      nucleosome sized pieces. Morphological analysis demonstrated that this death
      process is via apoptosis. During the apoptotic process induced by ionomycin,
      expression of cyclin-dependent kinase inhibitor p27Kip1 increased. Flow
      cytometric analysis showed that the treatment resulted in a block in G0/G1 of the
      cell cycle. These results demonstrate that even nonproliferating androgen
      independent prostatic cancer cells can be induced to undergo apoptosis if a
      modest elevation in the intracellular free calcium is sustained for a sufficient
      time. p27Kip1 protein is a candidate for the cell cycle regulator in ionomycin
      treated TSU-pr1 cells.

PMID- 9252653
TI  - Expression of CD44, ICAM-1 and N-CAM in colorectal cancer. Correlation with the
      tumor stage and the phenotypical characteristics of tumor-infiltrating
      lymphocytes.
AB  - The cellular adhesion molecules (CAMs) CD44s, CD44v6, CD44v10, ICAM-1 and N-CAM
      were immunohistologically detected in colorectal cancers using the APAAP method.
      The expression of CD44s and CD44v6 was associated with the presence of lymph node
      metastases in the examined tumors. The pattern of ICAM-1 expression was inversely
      related to that of CD44, i.e. lower numbers of ICAM-1 positive cells were
      observed in metastasizing tumors. An intense focal staining of N-CAM was observed
      in the majority of the metastasizing tumors. The expression of CD44v, ICAM-1 or N
      CAM on tumor cells did not correlate with the density of the tumor-infiltrating
      lymphocytes (TIL) within the tumors. The flowcytometric analysis of TIL showed a
      significant accumulation of CD25+ and HLA-DR+ cells and a reduced number of
      CD45RA+ cells as compared to autologous peripheral blood lymphocytes (PBL) or
      intraepithelial lymphocytes of the colon mucosa (IEL). These phenotypic
      characteristics of TIL did not correlate with the CAMexpression on tumor cells.

PMID- 9252655
TI  - Effect of methionine depletion on growth and apoptosis in various tumor cell
      lines.
AB  - Sodium ascorbate, sodium 5,6-benzylidene-L-ascorbate (SBA), gallic acid and
      caffeic acid induced apoptotic cell death in human myelogenous leukemic cell
      lines, and stimulated oxidation of methionine into methionine sulfoxide in the
      culture medium. When various tumor cell lines were cultured in methionine-free
      medium, their growth was nearly terminated at G1 phase of the cell cycle,
      producing much smaller number of apoptotic cells. Addition of methionine
      sulfoxide to the methionine-free medium did not stimulate the apoptosis
      induction. These data suggest that induction of apoptosis by ascorbates, gallate
      or by caffeate cannot be simply explained by methionine oxidation.

PMID- 9252654
TI  - Angiogenesis inhibitor TNP-470 augments the effect of repeated arterial ischemia
      on growth but does not affect take in a rat liver tumor model.
AB  - Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in
      the rat, but regrowth of tumor cells and capillaries takes place from the tumor
      periphery. It was therefore considered of interest to combine this treatment with
      the angiogenesis inhibitor TNP-470 (therapeutic model). Wistar rats with a
      dimethylhydrazine-induced adenocarcinoma implanted into the liver received one of
      the following treatments: TNP-470 + transient hepatic ischemia, transient hepatic
      ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one
      week after the start of treatment. In addition, we investigated if TNP-470
      decreases the risk of tumor take in the liver after intraportal injection of
      viable tumor cells (adjuvant study). Transient hepatic ischemia combined with TNP
      470 gave a smaller increase in tumor volume than transient hepatic ischemia (p <
      0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic
      ischemia or TNP-470 caused a significant suppression of tumor growth when
      compared to controls (p < 0.01 in both cases). In the adjuvant study, TNP-470
      caused retardation of tumor growth (p < 0.01 as compared to controls) but did not
      affect tumor number. It is concluded that TNP-470 suppressed tumor growth, both
      alone and in combination with transient hepatic ischemia, but did not affect take
      of tumor.

PMID- 9252656
TI  - Cytotoxicity of copper complexes of 2-furaldehyde oxime derivatives in murine and
      human tissue cultured cell lines.
AB  - The copper complexes of furan oxime derivatives were found to be potent cytotoxic
      agents in both murine and human tissue cultured cell lines which were either
      suspended or solid tumors. The ED50 values were frequently improved over the
      clinically useful antineoplastic agents. These copper complexes of 2-furaldehyde
      oximes were effective inhibitors of L1210 lymphoid leukemia DNA synthesis
      followed by RNA synthesis. Purine synthesis regulatory enzyme activities were
      markedly reduced by the compounds with marginal inhibition of t-RNA polymerase,
      and nucleoside kinases activities. L1210 DNA topoisomerase II activity was
      markedly reduced with IC50 values better than the standard VP-16, etoposide. Yet,
      the copper complexes caused no further protein linked breaks than VP-16 did, but
      did block phosphorylation activation of the topoisomerase II enzyme.

PMID- 9252657
TI  - Effects of Matrigel on the SF-767 malignant glioma athymic mouse tumor model.
AB  - Matrigel, an extracellular matrix material, has been used to promote growth of
      experimental tumors. SF-767, a human glioblastoma cell line, is used in brain
      tumor research. We investigated Matrigel induced changes in tumor latency, growth
      rate, cell yield, plating efficiency, and histology of SF-767 tumors in athymic
      mice. Low volume (0.1 ml) Matrigel did not increase growth rate in comparison
      with control tumors but appeared to promote uniformity in growth. High volume
      (0.5 ml) Matrigel increased the initial rate of tumor growth, increased cell
      yield and produced tumors with a centralized area of residual Matrigel and
      necrotic cells, with viable cells on the periphery of the mass. On average,
      tumors grown with Matrigel had shorter latency periods and lower plating
      efficiencies. We conclude that important characteristics of the SF-767 tumor
      model, which may be important when evaluating efficacy of anticancer agents, are
      altered by Matrigel.

PMID- 9252658
TI  - Antitumor activity of novel tricyclic pyrone analogs in murine leukemia cells in
      vitro.
AB  - New tricyclic pyrone derivatives were synthesized and tested for their ability to
      prevent L1210 leukemic cells from synthesizing DNA and growing in vitro. At 50
      microM, a pyripyropene analog has no effect, whereas four pentahydro-3-aryl-1
      oxopyrano[4,3-b][1]benzopyrans all inhibit DNA synthesis by 79-91% and tumor cell
      growth by 93-100%. These inhibitory effects are concentration dependent with IC50
      around 8.5 microM for DNA synthesis at 2 hours and 1.1 microM for tumor cell
      growth at 4 days. The aryl groups of these antitumor agents are either 3,4
      dimethoxyphenyl or 3-pyridyl. Introduction of a methyl group at C5a and a
      formyloxy or hydroxy group at C6 does not alter the antitumor effects of the 3,4
      dimethoxyphenyl benzopyrans but reduces those of the 3-pyridyl benzopyrans,
      which, at 50 microM, inhibit DNA synthesis by only 32-49% and fail to alter tumor
      cell growth. The 4-hydroxy-6-(3-pyridyl)-2-pyrone has no effect and the tricyclic
      pyrones lacking aryl groups have very little inhibitory effects on DNA synthesis,
      suggesting that a greater conjugation is required for the antitumor activity.
      These molecules have never been reported and might be valuable to develop a new
      class of anticancer drugs.

PMID- 9252659
TI  - Anticancer activities of 2,5,8,9-substituted 6-oxo-1,2,3,4,5,6
      hexahydrophenanthridines on multi-drug-resistant phenotype cells.
AB  - Lycorine is a member of the alkaloid group from the bulb of the amaryllidaceae.
      This drug has been reported to have anticancer activity. Several synthetic
      intermediates obtained during the synthetic study of anticancer drugs based on
      the lycorine structure, were tested for anticancer activity using three cell
      lines: L1210 and HL60 cell lines which were resistant (R) or sensitive (S) to
      adriamycin. The two synthetic intermediates, 2-acetoxy- and 2-hydroxy-5-allyl-8,9
      methylenedioxy-6-oxo-1,2,3,4,5,6-hexahydr ophenanthridine (1 and 2), both had
      anticancer activity in all three cell lines. However, the LD50 for the precursors
      was about 20 fold greater than for the native lycorine. Both 1 and 2 were
      cytotoxic to the adriamycin-resistant cell line, indicating that these drugs are
      not affected by the multidrug resistance factors. When low doses of the compounds
      were used, the HL60R cell line could be induced to differentiate to a cell which
      expressed a macrophage specific protein. These results suggest that
      phenanthridines 1 and 2 can be used on cells which are resistant to adriamycin,
      and that one mechanism of action is the induction of differentiation.

PMID- 9252660
TI  - Paracetamol counteracts docosahexaenoic acid-induced growth inhibition of A-427
      lung carcinoma cells and enhances tumor cell proliferation in vitro.
AB  - The belief that n-3 polyunsaturated fatty acids are in general cytotoxic to tumor
      cells appears not to be accurate. Of four tumor cell lines exposed to 35 microM
      docosahexaenoic acid (DHA, 22:6 n-3), we found only one (A-427, lung carcinoma)
      to be sensitive, whereas three (A-172, A549 and SK-LU-1) in fact were stimulated.
      A 6-fold higher level of lipid peroxidation in A549 as compared with A-427 cells
      indicates that cytotoxicity is not determined by the overall level of lipid
      peroxidation. Moreover, paracetamol (0.1, 0.3 and 1.5 mM), which is known to have
      both pro- and antioxidant activity, counteracted the cytotoxic effect of DHA on A
      427 cells in a dose-dependent manner by a mechanism that does not involve
      inhibition of overall lipid peroxidation. Although paracetamol (0.1 and 0.3 mM)
      in the absence of DHA was able to enhance proliferation of all tumor cell lines
      1.1-1.4-fold, this was insufficient to explain the ability of the drug to protect
      against DHA-induced cytotoxicity. Neither did paracetamol cause major changes to
      the activity of the defense enzyme glutathione peroxidase, known to play a role
      in the sensitivity of A-427 cells to DHA. Paracetamol could possibly act by
      reacting with minor, highly toxic, peroxidation products, or alternatively, by
      altering the substrate for lipid peroxidation, i.e. the fatty acid composition of
      the membranes, in favor of less toxic products.

PMID- 9252661
TI  - A streptococcal preparation (OK-432) enhances monoclonal antibody NCC-ST-421
      cytotoxicity against human colon cancer.
AB  - The murine IgG3 monoclonal antibody NCC-ST-421 (ST-421), raised against human
      gastric cancer, shows strong reactivity with the Le(a)/Le(a) (al-fucosylated
      extended type 1 chain) antigen expressed on gastrointestinal (GI) cancer cells.
      ST-421 is capable of mediating both antibody-dependent cellular cytotoxicity
      (ADCC) by human peripheral blood lymphocytes (PBL), and complement dependent
      cytotoxicity (CDC). We investigated combination immunotherapy with OK-432, a
      streptococcal preparation, and ST-421 in vitro and in vivo. ADCC against Colo 205
      (a human colon cancer cell line) was enhanced 2 to 3 fold after preincubation of
      PBL with OK-432 in vitro. These effect's were strongest when PBL were
      preincubated with OK-432 at a concentration of 0.5 ng/ml for 24 hours. In vivo, a
      human colon cancer xenograft model exhibited significant growth suppression after
      combined treatment with ST-421 and OK-432. Such combination immunotherapy may
      therefore be clinically useful in GI cancer.

PMID- 9252662
TI  - Inhibitory effects of telomere-mimic phosphorothioate oligonucleotides on various
      human tumor cells in vitro.
AB  - We tested the cell growth inhibitory effects of telomere-mimic oligomers, 5'
      d(TTAGGG)n-3' where n = 1, 2, 3 or 4 in the following 8 human tumor cell lines:
      2780 ovarian carcinoma, HEp-2 squamous cell carcinoma, VAMT-1 mesothelioma, DND
      1A melanoma, MOLT-3 ALL, Jurkat lymphoma, Daudi Burkitt lymphoma, and JAR
      choriocarcinoma. As controls, 1 scrambled 6-mer and 2 scrambled 24-mers were
      tested. Among the compounds tested, the 6-mer and 12-mer were not active in any
      of the cell lines studied. Increases in the length of oligonucleotides from 18-
      to 24-mer resulted in increased cell growth inhibitory activity in sensitive cell
      lines. Cells in suspension cultures, MOLT-3 ALL and Daudi Burkitt lymphoma were
      generally more sensitive than the monolayers (24-mer ID90 = -3 microM). While the
      inhibitory effects of authentic 24-mer oligomer were more pronounced than the
      scrambled oligomers, both of the scrambled 24-mers also showed some degree of
      inhibitory activity. Except for modest activity of the 24-mer in 2 cell lines,
      DND-1A and 2780, none of the compounds tested were active against solid tumor
      cell lines. These data indicate that further study of the telomere-mimic 24-mer
      is warranted as candidate compound for the treatment of leukemia/lymphoma.

PMID- 9252663
TI  - Effect of Trolox, a synthetic analog of alpha-tocopherol, on cytotoxicity induced
      by UV irradiation and antioxidants.
AB  - The addition of Trolox, a synthetic analog of alpha-tocopherol, significantly
      reduced the cytotoxicity induced by UV irradiation and antioxidants, such as
      ascorbate, gallate and caffeate. Ascorbate and gallate, but not UV irradiation,
      stimulated the oxidation of methionine to methionine sulfoxide in the culture
      medium, possibly because of their prooxidant actions. Trolox slightly, but
      significantly reduced the methionine oxidation. On the other hand, alpha
      tocopherol showed a much lower protective effect against ascorbate and gallate
      induced cytotoxicity, and failed to reduce the methionine oxidation induced by
      these agents. ESR spectroscopy showed that both Trolox and alpha-tocopherol did
      not significantly change the radical intensity of ascorbate and gallate. The
      present study suggests that the antioxidative efficacy of Trolox surpasses that
      of alpha-tocopherol.

PMID- 9252664
TI  - Radical intensity and differentiation-inducing activity of benzo[a]phenothiazines
      and phenothiazines.
AB  - ESR spectroscopy revealed that 12H-benzo [a]phenothiazine, 9-methyl-12H
      benzo[a]phenothiazine, 10-methyl-12H-benzo [a]phenothiazine, 11-methyl-12H
      benzo[a]phenothiazine and 5-axo-5H-benzo[a]phenothiazine, which induced the
      differentiation of human myelogenous leukemic cell lines into maturing
      macrophages, produced radical(s) under an alkaline condition. On the other hand,
      6-hydroxy-5-axo-5H-benzo [a]phenothiazine, 6-methyl-5-oxo-5H
      benzo[a]phenothiazine and 5H-benzo[a][1,4]benzothiazino-[3,2-c]phenothiazine, and
      13 phenothiazines, which had little or no differentiation-inducing activity,
      produced no detectable amounts of radical(s). Using Huckel molecular orbital
      (HMO) method, these active benzo[a]phenothiazines were shown to have the elevated
      n-spin density at the sulfur atom of their molecules. Seven out of 8
      benzo[a]phenothiazines significantly enhanced the radical intensity of sodium L
      ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA), whereas only 3 out of 13
      phenothiazines showed similar effects. These data suggest that the induction of
      human leukemic cell differentiation by benzo[a]phenothiazines might be initiated
      by radical mediated reactions.

PMID- 9252665
TI  - A model for osseous metastasis of human breast cancer established by intrafemur
      injection of the MDA-MB-435 cells in nude mice.
AB  - BACKGROUND: A nude mouse model was developed and studied for temporal
      pathogenesis of bony metastasis of human breast cancer. MATERIALS AND METHODS:
      Human breast cancer cells, MDA-MB-435, were injected into the medulla of left
      femurs of 10 Beige nude mice, whereas their right femurs were similarly injected
      with phosphate buffered saline as a control. The mice were killed at 1 week
      intervals for up to 5 weeks. RESULTS: Tumors appeared in all the animals 3 weeks
      after the injection: they began to appear in the medulla at 2 weeks, and invasion
      of the tumor into the cortex and surrounding tissues of the bone appeared at 4
      weeks. Both osteolytic and osteoblastic activation frequently observed in the
      affected bone of breast cancer patients were present. CONCLUSION: This model
      produces a high incidence of bony metastasis and may be appropriate for the study
      of osseous metastasis of this human disease.

PMID- 9252666
TI  - Taxane sensitivity of ovarian carcinoma in vitro.
AB  - Paclitaxel, the first clinically available taxane, has proven to be effective in
      the treatment of ovarian carcinoma. Docetaxel is the second taxoid derivative
      which has also shown activity in ovarian carcinoma. These two compounds have
      clear differences in pharmacokinetics and side-effects. In the present study we
      have tested the cytotoxic effect of docetaxel in seven ovarian carcinoma cell
      lines using the 96-well plate clonogenic assay. These results have been compared
      with data obtained from our recent study on cisplatin and paclitaxel
      sensitivities of the same cell lines. Chemosensitivity has been expressed as IC50
      value, the drug concentration causing 50% inhibition of clonogenic survival. The
      IC50 values for docetaxel were 0.23-2.30 nM showing a 10-fold difference between
      individual cell lines. On a molar basis, docetaxel was 1.2 to 2.6 times more
      active than paclitaxel in six out of seven cell lines. This may be explained by
      differences in the mechanism of action or by differences in other pharmacological
      properties.

PMID- 9252667
TI  - Detection of rare circulating breast cancer cells by filtration cytometry and
      identification by DNA content: sensitivity in an experimental model.
AB  - Current methods of detecting micrometastases in breast cancer fail in a large
      proportion of patients. Therefore an improved method for detection of metastases
      in blood samples could be of great clinical interest both for prognosis and
      selection of patients for adjuvant systemic therapy. We have developed a new non
      invasive method which associates immuno-magnetic separation and filtration
      cytometry. The sensitivity of our procedure was evaluated in a model system using
      a mixture from a human breast cancer cell line (MCF-7) and a normal human blood
      sample. The identification of tumoral cells was achieved by measuring DNA content
      in comparison with standard cells. The lowest concentration of MCF-7 detected was
      1 tumoral cell in 500,000 white blood cells. In addition, filtration cytometry
      provides a visual control of nuclei permitting the elimination of all doubtful
      cases and an automatic count of tumoral cells directly per ml of blood, which may
      be an independent predictor of early relapse. This new method may avoid
      unnecessary axillary lymph node dissection in patients with negative nodes. Our
      procedure seems suitable for the detection of rare circulating cells in routine
      laboratory testing and could be used in other applications.

PMID- 9252668
TI  - Copper, but not iron, enhances apoptosis-inducing activity of antioxidants.
AB  - Addition of either CuCl or CuCl2 significantly enhanced sodium ascorbate or
      sodium 5,6-benzylidene-L-ascorbate (SBA)-induced cytotoxicity and
      internucleosomal DNA cleavage in human promyelocytic leukemic HL-60 cells. On the
      other hand, the addition of either FeCl2 or FeCl3 inhibited the cytotoxic
      activity of ascorbate. These effects were observed even if the cells were exposed
      for only 20 minutes to metals and ascorbates. Copper also stimulated the gallate
      or caffeate-induced apoptotic cell death, whereas iron was inhibitory. Both
      copper and iron enhanced the radical intensity of ascorbates, but slightly
      reduced the radical intensity of gallate and caffeate, suggesting that radical
      intensity is not the sole determinant of apoptosis induction. Metals did not
      significantly change the methionine oxidation stimulated by ascorbate, gallate or
      caffeate. Methionine oxidation may not be indispensable for antioxidant-induced
      apoptosis.

PMID- 9252669
TI  - Paclitaxel and N-methylformamide: in vitro interactions in human colon cancer
      cell line.
AB  - The combination of differentiation-inducing agents with conventional
      antineoplastic drugs has been suggested as a potential new cancer therapeutic
      approach. We have assayed the cytotoxic effect of N-Methylformamide (NMF) as a
      differentiating agent combined with Paclitaxel, a novel antineoplastic agent, on
      cell survival of a human adenocarcinoma cell line HT29. The cell killing of this
      combination was evaluated by clonogenic assay and cell cycle perturbation was
      analyzed by flow cytometric methods. HT29 cells were exposed to graded doses of
      Paclitaxel (0.001-0.01-0.1-1-5 micrograms/ml) for 2, 4, 8, 16, 18 and 24 hours in
      order to determine its dose-time effect. Secondly, exponentially or non-growing
      HT29 cells were exposed to graded doses of Paclitaxel (0.001-5 micrograms/ml) for
      18 hours at 37 degrees C, and in combination experiments the cells were pre- or
      posttreated with 1% NMF for 72 hours. The results demonstrated that only
      proliferating cells were responsive to Paclitaxel and that its cytotoxicity is
      strictly related to exposure time. The combination studies showed that only the
      Paclitaxel-->NMF sequence causes a powerful reduction in the surviving fraction
      of HT29 cells, whereas the reverse sequence had a protective effect on cell
      killing. The flow cytometry evaluation has indicated that synergism with NMF in
      HT29 cells was observed only at the same Paclitaxel concentrations required for
      mitotic arrest, suggesting that the mechanism underlying the synergic interaction
      was a Paclitaxel-induced alteration of cell cycle kinetics. This study stresses
      the importance of the administration sequence in the protocols involving NMF as a
      cytotoxic effect modulator as well as the role of cell kinetics in determining
      the effectiveness of this modulation.

PMID- 9252670
TI  - Prognostic significance of apoptosis related proteins Bcl-2 and Bax in node
      negative breast cancer patients.
AB  - In this immunohistochemical study we investigated the expression of Bcl-2 and Bax
      apoptosis related proteins in node-negative breast carcinomas. The results were
      correlated with the recurrence rate of the patients. In order to avoid the
      influence of the most important tumor prognostic parameters we selected two
      groups of node negative breast ductal carcinomas that were grade II according to
      Bloom and Richardson classification, had a diameter of 1-3 cm but differed in
      clinical outcome: 44 of the patients had a 10 year disease-free survival while 46
      developed metastatic disease in the same period of time. Bcl-2 and to a lesser
      degree Bax expression were inversely related with distant metastases (Pbcl-2 =
      0.007, Pbax = 0.03). Combined analysis of Bax/Bcl-2 expression in relation to
      clinical outcome showed that the absence of both factors was more strongly
      associated with the development of distant metastases (P = 0.006, Ptrend =
      0.001). Our findings indicate that Bcl-2 and Bax apoptosis-related proteins are
      good indicators of prognosis in node-negative breast cancer patients, and their
      combined absence, suggestive of serious deregulation of the apoptotic process,
      may contribute to the biologic aggressiveness of the tumors.

PMID- 9252671
TI  - Cytochemical demonstration of nitric oxide synthase and 5' nucleotidase in human
      glioblastoma.
AB  - Both nitric oxide (NO), formed from L-arginine by the enzyme nitric oxide
      synthase (NOS), and adenosine, which is produced by 5' nucleotidase (5' N) acting
      on adenosine 5' monophosphate (5' AMP) are implicated in several
      neurophysiological processes. In addition, 5' N is a linker protein involved in
      cell motility. Alterations of both enzyme activities seem to be responsible for
      some pathological states of the central nervous system (CNS). In the present
      report, we have studied the cytochemical demonstration of NOS and 5' N activities
      in human glioblastoma cells. Enzyme activity of both was observed in tumor cells;
      moreover, the coincidence of enzyme histochemistry and immunohistochemistry for
      NOS was noted in most cases. The findings were interpreted on the basis of the
      cytotoxic effects due to NO production by tumor cells, and on the non-catalytic
      role of membrane 5' N which acting as an adhesive molecule can favour tumor
      invasiveness.

PMID- 9252672
TI  - 31P NMR spectroscopy of photodynamically treated cells.
AB  - The metabolic response of Chinese Hamster Ovary (CHO) cells during photodynamic
      therapy (PDT) with hematoporphyrin IX (Hp IX) and pheophorbide (Ph) was monitored
      in real time by 31-phosphorous (31P) nuclear magnetic resonance (NMR)
      spectroscopy. The effects of the delivered light dose and of cell oxygenation
      were investigated. A delayed disappearance of nucleoside triphosphate (NTP)
      following irradiation was observed, which was related to the treatment
      efficiency. For cells irradiated with a light dose of 0.8 J/cm2 in the presence
      of Hp IX, the disappearance of the NTP peaks occurred within 30 minutes of
      irradiation, but for an irradiation of 0.24 J/cm2, the disappearance of the NTP
      peaks occurred about 6 hours later, and this delayed disappearance is related to
      the surviving fraction. For irradiation experiments involving Ph and a light dose
      of 0.036 J/cm2, NTP in injured cells began to decrease about 3 hours after
      irradiation, whereas for a light dose of 0.24 J/cm2, we observed the
      instantaneous disappearance of the NTP peaks occurring during the irradiation
      time. The same efficiency was obtained with two different oxygen partial
      pressures in the perfusate (360 and 154 mmHg) and a light dose of 0.24 J/cm2.

PMID- 9252673
TI  - Advances in the understanding of lung cancer.
AB  - Lung cancers still represent an incurable group of malignancies, where we have to
      admit that therapy, be it surgery, chemotherapy or radiation, still fails. The
      emphasis in research has centered on exogenous factors causing the initiation and
      progression of the different types of lung cancer, especially exposure to tobacco
      smoke. But so far we have learned that endogenous factors play an equal, if not a
      more important role, in the onset of this group of diseases. Cancer arising
      spontaneously never appears to be due to one specific factor, but experimental
      cancers have been shown to do so. In this light, recent advances in molecular
      biology have pointed out the relevance of the role of oncogenes and tumor
      suppressor genes in the pathogenesis of lung cancers. It is the purpose of this
      paper to review these latest findings, especially from a genetic point of view.

PMID- 9252674
TI  - Modulation of natural killer cell functional activity in athymic mice by beta
      carotene, oestrone and their association.
AB  - In athymic mice, Natural Killer (NK) cells influence the take rate and growth of
      human malignant tissue xenografts. To confirm preliminary results, comparative
      experiments were conducted to study the effects of beta-carotene, oestrone and
      their association on the cytolysis mediated by spleen NK cells from athymic mice
      receiving these different treatments. Target cells consisted of YAC-1 malignant
      cells. With a 65% increase of cytolysis (ratio effector/target 50:1), beta
      carotene induced a significant activation of NK cells (p < 0.002). This effect
      could be attributed to its antioxidant properties and confirmed by a moderate
      increase in erythrocyte glutathione peroxidase activity. On the contrary,
      oestrone resulted in a significant decrease of cytolysis (p < 0.001). In this
      case, the prooxidant properties of oestrone could explain its effect on NK cells
      and agree with the increase of intracellular reduced glutathione level observed.
      When mice received the combination beta-carotene-oestrone, their opposite effects
      on NK cell activity were counterbalanced, leading to a moderate change of
      cytolysis.

PMID- 9252675
TI  - Non-transferrin-bound iron and tumor cells.
AB  - The study of iron uptake from low molecular weight complexes by Ehrlich carcinoma
      cells shows concentration-dependence, and ATP increases the iron uptake from
      citrate and lactate complexes. Blood proteins can act as inhibitors, and
      deferoxamine chelation of cell-bound iron complex indicates that the percentage
      of iron penetrating the cell is about the same for a wide range of iron complex
      concentrations in the incubation medium (about 5% for ferric lactate). Ascorbic
      acid increases iron uptake and simultaneously decreases lipid peroxidation.
      Electrophoresis shows a very high iron transfer from ferric lactate to ATP, and
      to a lesser extent to ADP and AMP. In the pathological evolution of iron overload
      to a neoplasia, the probable involvement of an iron exchange between iron
      complexes from non-transferrin-bound iron of plasma and ATP is discussed.

PMID- 9252676
TI  - Antitumor effect of carboplatin combined with radiation on tumors in mice.
AB  - The antitumor effect of cis-diammine-1, 1-cyclobutane dicarboxylate platinum(II)
      (CBDCA, Carboplatin) and radiation on Ehrlich ascites tumors was evaluated in CD
      1 mice. A single dose of CBDCA was combined with a single dose of radiation. The
      antitumor effect was evaluated by tumor volume. Inhibition of tumor growth by the
      combination of CBDCA and radiation was greater than by CBDCA and radiation alone.
      The most effective condition was the simultaneous combination of CBDCA with
      radiation. Further, we examined the radiation influence on the concentration of
      platinum in tumor tissue. We found that when CBDCA was administered after
      irradiation, the concentration of platinum in tumor tissue decreased
      proportionally with time.

PMID- 9252677
TI  - Radical modulation activity of benzo[a]phenothiazine.
AB  - 12H-Benzo[a]phenothiazine generated radical(s) under alkaline conditions, and
      enhanced the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L
      ascorbate. Phenothiazine and chlorpromazine hydrochloride did not produce
      radicals, nor affect the radical intensity of ascorbates. 12H
      Benzo[a]phenothiazine scavenged the superoxide anion and hydroxyl radical, more
      efficiently than phenothiazine and chlorpromazine hydrochloride. The radical
      modulation activity of 12H-benzo[a]phenothiazine might explain at least in part
      the ability of this compound to induce monocytic differentiation and apoptosis in
      human myelogenous leukemic cell lines.

PMID- 9252678
TI  - Glycophorin-induced differentiation of human myelogenous leukemic cell lines.
AB  - Human myelogenous leukemic cell lines, U-937, ML-1, and THP-1, were induced to
      differentiate into maturing macrophage-like cells upon treatment with any
      glycophorins from either human, monkey or cow erythrocyte membrane. The
      differentiated cells expressed lower growth potential, and higher nitroblue
      tetrazolium-reducing activity, Fc-receptor, phagocytic activity and non-specific
      esterase activity. The differentiation-inducing activities of the glycophorins
      were significantly reduced after neuraminidase treatment. On the other hand,
      sialic acid and colominic acid (a polymer of sialic acid) were inactive. These
      results suggest that some conformational requirement involving the linkage of
      sialic acid residues in the glycoproteins is necessary for the observed
      differentiation-inducing activity.

PMID- 9252679
TI  - In vivo growth regulation by cytokine in breast cancer cells showing an estradiol
      inhibitive response in vitro.
AB  - The rates of the stimulative, insensitive, and inhibitive responses to 10(-2) nM
      E2 in sixty clinical breast cancer cases were 24.2%, 45.2%, and 30.6%,
      respectively. We then examined the expression of mRNAs of such cytokines as TNF
      alpha, TGF-alpha, EGF, and TGF-beta, in cancer tissue specimens from these three
      different groups. In MCF-7 showing an E2-stimulative response, the expression of
      mRNAs of both TNF-alpha and TGF-alpha were suppressed by 10(-2) nM E2, but these
      same expressions in KSE-1 showing an E2 stimulative response were enhanced by E2.
      The mRNA expression of TGF-beta in these two cell lines was suppressed by 10(-2)
      nM E2, but that of EGF was enhanced. In clinical cases showing an E2-inhibitive
      response, the mRNA expression ratio of TNF-alpha/TGF-beta was above 2.5, but
      under 2.5 in E2-uninhibitive response cases. The mRNA expression ratio of TGF
      alpha/TGF-beta was over 1.8 in the E2-inhibitive responsive cases, but under 1.8
      in the E2-uninhibitive response cases. The mRNA expression ratio of EGF/TGF-beta
      did not show any regular tendency in three groups showing a different E2-response
      in vitro. Based on in vitro results and mRNA expression in clinical cases, the
      cytokine expression for E2-inhibitive cancer cells differed from those of E2
      stimulative and -insensitive cells. Therefore, E2-inhibitive cancer cells are
      thus considered to possibly possess a characteristic growth regulation which is
      different from that for E2-uninhibitive cancer cells.

PMID- 9252680
TI  - Inhibition of farnesyl protein transferase by monoterpene, curcumin derivatives
      and gallotannin.
AB  - Ras proteins must be isoprenylated at a conserved cysteine residue near the
      carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to extend
      their biological activity. Previous studies have indicate an intermediate in the
      mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this
      isoprenyl group, and that using inhibitors of the mevalonate pathway could block
      the transforming properties of ras oncogene. Unfortunately, mevalonate is a
      precursor of various end products essential to mammalian cells, such as
      dolichols, ubiquinones, heme A, and cholesterol. In this study, we partially
      purified farnesyl protein transferase (FPTase) capable of catalyzing the
      farnesylation of unprocessed Ras p21 proteins in vitro from porcine kidney
      epithelial-like LLC-PK 1 cells, human lung adenocarcinoma A549 cells and human
      pancreatic cancer MIA PaCa-2 cells. This FPTase activity requires a divalent
      cation, such as Mg2+ or Zn2+ ions, sulfhydryl protecting agent, DTT, as well as
      certain pH which is linear with time and with enzyme concentration, and is
      present in many mammalian normal cell and tumor cell lines. Sequentially, we
      observed the effects of the monoterpene compound, d-limonene; curcumin
      derivatives, CD-I and CD-II; polyphenol compound, gallotannin; Salvia
      miltiorrhiza derivative, SMD; and retinoid acid derivative, RAD on FPTase
      activity. We found that curcumin derivatives and gallotannin had a strong
      inhibition on FPTase besides d-limonene, while gallotannin was the strongest
      among synthetic and natural compounds tested. Salivia miltiorrhiza and retinoid
      acid derivatives had no influence on FPTase activity. Our results suggest that
      compounds containing polyphenol hydroxyl may be a new source of FPTase
      inhibitors. The experiment also showed that availability of an in vitro farnesyl
      protein transferase assay could be useful in screening for potential inhibitors
      of ras oncogene function that will not interfere with other aspects of the
      mevalonate pathway.

PMID- 9252681
TI  - Methionine oxidation and apoptosis induction by ascorbate, gallate and hydrogen
      peroxide.
AB  - Addition of either ascorbate, gallate, caffeate or hydrogen peroxide to the
      culture medium stimulated the oxidation of free methionine to methionine
      sulfoxide, regardless of the presence or absence of the cells. In methionine-free
      medium, growth of human myelogenous leukemic cell lines was nearly stopped by G1
      arrest, without induction of internucleosomal DNA cleavage. Methionine sulfoxide,
      a major oxidation product of methionine, was neither growth-promoting nor
      cytotoxic. On the other hand, methional, a deamination and decarboxylation
      product of methionine, was highly cytotoxic. The present study suggests that the
      apoptosis induction by these antioxidants and oxidant cannot simply be explained
      by methionine oxidation or depletion.

PMID- 9252682
TI  - Immunohistochemical expression of p53, bcl-2, mdm2 and waf1/p21 proteins in
      colorectal adenocarcinomas.
AB  - The present study was undertaken to examine the distribution of p53, p21, mdm-2
      and bcl-2 protein expression in human colorectal adenocarcinomas in order to
      obtain combined information about the immunophenotypes characterising these
      tumours. Formalin-fixed, paraffin-embedded tissue sections from 52 cases of
      colorectal adenocarcinomas were stained using immunohistochemical methods for the
      detection of p53, p21/waf1, mdm2 and bcl-2 proteins. P53, p21/waf1, mdm2 and bcl
      2 proteins were expressed in 35/52, 45/52, 9/52 and 27/52 cases, respectively.
      All nine mdm2+ cases expressed p53 and p21 proteins as well. The three patterns
      observed in p53/p21 expression were: p53+/p21+, p53+/p21- and p53-/p21+ in 28, 7,
      and 17 cases, respectively. Consequently, p53+/mdm2-/p21+, p53+/mdm-/p21- and p53
      /mdm2-/p21+ immunophenotypes were expressed in 19, 7, and 17 cases respectively.
      Four patterns of p53/bcl2 expression were identified: p53+/bcl2+, 20 cases;
      p53+/bcl2-, 15 cases; p53-/bcl2+, 7 cases; p53-/bcl2-, 10 cases. It was
      noteworthy that 9 of the 10 p53-/bcl2-tumours had negative lymph node status. The
      present results suggest that both p53 dependent and p53-independent induction of
      p21 expression may be involved in the molecular mechanisms controlling these
      tumours. High expression of the p53 protein in colorectal carcinomas could be due
      not only to p53 gene mutations but also to binding to mdm2 protein which leads to
      p53 protein stabilisation. In addition, tumours with p53-/bcl2- immunophenotype
      are frequently associated to negative lymph node status and seem to be less
      aggressive.

PMID- 9252683
TI  - Immunocytochemical detection of prostate specific antigen expression in human
      breast carcinoma cells.
AB  - To date, no true tissue specific antigen has been discovered. Prostate-specific
      antigen (PSA) was initially reported to be a tissue specific protein, detected in
      the seminal fluid and produced by normal and abnormal epithelial cells of the
      prostate gland. PSA is a 33 kD glycoprotein, with serine protease activity, and
      it is produced by several different tissues in the human body. Its expression
      levels may be elevated during benign and neoplastic cell growth in the prostate,
      and in a number of other human malignancies. The detection of PSA is also useful
      in monitoring the efficacy of anticancer treatment in malignant prostatic
      adenocarcinoma. In the present immunocytochemical study, PSA expression was
      examined employing a biotin-streptavidin based, alkaline phosphatase conjugated
      antigen detection technique in 16 routine, neutral formalin fixed, paraffin-wax
      embedded, primary BC tissue sections. Human postnatal thymic tissue, among
      others, was used as a negative tissue control, while normal prostate and prostate
      carcinomas (PCs) were included in the collection of antigen positive tissues. We
      observed the presence of PSA in all 16 BC cases, and this expression was
      independent of estrogen receptor status. The intensity of the staining was
      moderate to high (B to A) and localized to 20% to 40% of the total BC cell
      population, with cells of similar immunoreactivity being clustered in groups
      within the tumor microenvironment. This result directly contradicts the previous
      opinion concerning the prostate epithelium specificity of PSA expression and
      production. The immunophenotype (IP) heterogeneity of BC cells is further
      substantiated by their PSA positivity and its association with the presence of
      steroid hormone receptors. The establishment of the clinical significance of
      these findings necessitates further in vivo and in vitro research in BCs. The
      prognostic significance of PSA in BCs may lie in the identification of a subset
      of estrogen receptor negative BC patients who have malignancies associated with a
      good prognosis. PSA related, novel antineoplastic immunotherapy may also be
      recommended.

PMID- 9252684
TI  - P-glycoprotein mediated multidrug resistance assessment by flow-cytometry in
      malignant hemopathies.
AB  - A relatively common and frequent form of multidrug resistance(MDR) in cancer
      cells is due to membrane overexpression of P-glycoprotein. Mdr phenotype was
      investigated by flow-cytometry in several types of malignant hemopathies -chronic
      lymphocytic leukemia, non-Hodgkin lymphomas, acute lymphoblastic and myeloblastic
      leukemias. We used daunomycin and fluo-3 as fluorochromes, and verapamil as
      reversor agent. The method is lacking unitary clinical parametrization and in
      order to improve it, we tried to establish an optimal concentration of verapamil,
      which was shown to be 14.92 micrograms/ml. The reliability of results obtained
      with fluo-3 in culture media containing Ca2+ is questionable, as low variations
      in the intracellular level of this ion dramatically influences light emission by
      the fluorochrome and possibly the function of P-gp. To avoid such fluorescence
      intensity variations, Ca(2+)-free cell culture medium for fluo-3-based flow
      cytometric assay is suggested to be used.

PMID- 9252686
TI  - Retinoblastoma (pRb) protein immunoexpression in colorectal cancer.
AB  - The level of expression of the cell cycle regulatory proteins is an important
      facet in determining the malignant state. Fifty consecutive colectomy specimens
      of colorectal carcinoma in patients over 50 years of age, and 25 cases in
      patients under 30 years, were examined to ascertain retinoblastoma protein
      expression and to relate this to clinicopathological features. Retinoblastoma
      protein (pRb) staining was more intense in well differentiated, low stage
      carcinomas in the over 50 age group (p < 0.001). On the other hand, in the under
      30 age group, pRb staining was seen in all tumours grades and stages. No
      statistical significance was noted with other clinical or pathological features
      in both age groups.

PMID- 9252685
TI  - Papillary cystic tumors of the pancreas: assessment of malignant potential by
      analysis of progesterone receptor, flow cytometry, and ras oncogene mutation.
AB  - BACKGROUND: Although the biologic behavior of papillary cystic tumor (PCT) of the
      pancreas is more favorable than the adenocarcinoma, a malignant form has been
      reported. There has been much controversy as to the histologic evidence for
      malignancy. The purpose of this study is to evaluate whether the ras oncogene
      mutation is present in the PCT, together with hormone receptor status and DNA
      flow cytometry that can be used to predict tumor aggressiveness. MATERIALS AND
      METHODS: In 6 collected cases of PCT, estrogen receptors (ER) and progesterone
      receptors (PR) were detected by immunohistochemical techniques, DNA ploidy and S
      phase fraction (SPF) were studied by flow cytometry, and H, K, and N-ras oncogene
      mutation were analyzed by polymerase chain reaction (PCR). RESULTS: General
      strong positive immunostaining of PR and negative staining of ER are found in all
      6 cases of PCT, including 5 adolescent girls and one 55-year-old women with areas
      of anaplastic transformation. Flow cytometry analysis revealed diploid DNA in all
      6 cases but higher SPF in the anaplastic portion of the old one. None of the 6
      cases showed H-, K-, or N-ras oncogene mutation. CONCLUSIONS: These results
      suggest PR status and ras oncogene mutation appear to be not useful in predicting
      aggressive behavior. DNA ploidy and S-phase fraction may provide useful
      information for prognosis, but their more precise prognostic value of PCT needs a
      larger number of cases to clarify.

PMID- 9252687
TI  - Differentiation of human fibroblasts to tissue macrophages by the Snyder-Theilen
      feline sarcoma virus (ST:FeSV): growth modulation of human tumor cell lines in
      agar.
AB  - BACKGROUND: Snyder-Theilen feline sarcoma virus (ST:FeSV)-transduced human
      fibroblasts differentiate into tissue macrophages(1-9). The ST:FeSV-induced
      macrophages demonstrate macrophage-mediated cytotoxicity (MTC) and antibody
      dependent cellular cytotoxicity (ADCC), including growth modulation of tumor
      cells in agar (3,4,6). MATERIALS AND METHODS: Here we tested the effects of
      ST:FeSV-induced macrophages in agar on the following human tumor cell lines:
      colon adenocarcinoma, prostate adenocarcinoma, breast adenocarcinoma, malignant
      melanoma, leiomyosarcoma, fibrosarcoma, and fibrous histiocytoma. The tumor cells
      were co-incubated in agar with ST:FeSV-induced macrophages in the absence or
      presence of 10% fetal bovine serum (FBS). RESULTS: Regardless of serum
      conditions, the growth of all tumor cells tested was inhibited considerably by
      the ST:FeSV-induced macrophages. Colon adenocarcinoma cells were the least
      affected, and fibrosarcoma or fibrous histiocytoma cells were the most sensitive
      to growth inhibition by the ST:FeSV-induced macrophages. A notable exception was
      the growth stimulation of breast adenocarcinoma (BT-20; MCF-7), and of prostate
      adenocarcinoma (TSU-prl) tumor cell lines by the ST:FeSV-induced macrophages in
      the absence of FBS. CONCLUSIONS: The results attest to the potency of secreted
      proteins that are expressed by ST:FeSVinduced macrophages which can modulate
      tumor cell growth in agar. The results further indicate that serum is likely to
      have an impact on the effects of these growth regulatory factors on human tumor
      cells.

PMID- 9252688
TI  - Comparative and environmental genotoxicity of antimony and arsenic.
AB  - Antimony and arsenic compounds are known to have a genotoxic potential. Soil
      contamination with these elements can be due to the presence of natural ore
      sources of fahlore (gray copper). As a result, human and animal populations may
      be highly exposed. The sister chromatid exchange (SCE) test is an adequate tool
      for the sensitive detection of antimony and arsenic genotoxicity. We used this
      assay to investigate the coergism of the two elements in vitro to gain data for
      the assessment of a putative risk from coexposure. The combinative effect of
      antimony and arsenic in the SCE test appeared subadditive. Additionally, the SCE
      served to determine the genotoxic potential in extracts of contaminated fahlore
      soil samples gained under mildly acidic conditions. The genotoxicity observed was
      very low because antimony and arsenic predominated in the pentavalent, non
      genotoxic state, but, the partial antagonism observed in the in vitro experiments
      could be an additional explanation for the low genotoxicity.

PMID- 9252689
TI  - Modulation of apoptosis signaling in etoposide-treated lymphoma cells.
AB  - Signals of etoposide (ETO) induced apoptosis were studied in a human (B) lymphoma
      cell line, HT58. Morphology and DNA fragmentation assays proved the appearance of
      apoptosis after a short ETO treatment (4 hours). Modulation of signal components
      of this apoptotic pathway resulted the following a) phorbol ester (PMA) or heat
      shock inhibited apoptosis, which was prevented by staurosporine b) 3-amino
      benzamide, a potent poly(ADP-ribose)polymerase inhibitor, had no significant
      effect; c) cysteine reactive compounds, such as iodoacetamide and phenylarsine
      oxide, as well as protease inhibitor TPCK were very active inhibitors of
      apoptosis; d) protein synthesis inhibitor, cycloheximide, potentiated cell death;
      e) the ETO-induced p53 protein overexpression had neither enhancing nor
      protecting effect on the apoptotic process. In conclusion, in the majority of
      HT58 lymphoma cells the apoptotic machinery is "primed" (the components are
      already expressed) and ETO-induced apoptosis is regulated by STA sensitive
      phosphorylation and proteolysis by cystein proteases, but not affected by ADP
      ribozylation or p53.

PMID- 9252690
TI  - P21/waf1 protein expression in nasopharyngeal carcinoma. Comparative study with
      PCNA, p53 and MDM-2 protein expression.
AB  - We investigated the immunohistochemical expression of p21/waf1 protein in 59
      cases of nasopharyngeal carcinomas (NPC) and compared p21 expression with PCNA,
      p53 and mdm2 protein expression. We found p21, PCNA, p53 and mdm2 in 59/59,
      59/59, 18/59 and 12/59 nasopharyngeal carcinomas, respectively. We observed a
      tendency to a relationship between high expression of PCNA (> 25% positivity in
      tumour cells) and low expression of p21 protein. Parallel p53/p21 protein
      expression was found in 18 cases. Twelve were also mdm2 positive. This pattern
      may represent NPC with wild type (wt) p53 since mdm2 and p21 proteins are
      inducible by wt p53 gene. In these cases p53 protein expression may be due to
      stabilisation to mdm2 protein. This could be important in the pathogenesis of
      these cases since mdm2 may deregulate the p53-dependent growth suppressive
      pathway. Discordant p53-/p21+ protein expression was found in 41 cases. All were
      also mdm2 negative. This pattern suggests immunohistochemically undetectable wt
      p53 gene which is able to induce p21 protein expression.

PMID- 9252691
TI  - Cytotoxic properties of a phosphoglycoconjugated derivative of 7 beta
      hydroxycholesterol upon normal and tumor cells in culture.
AB  - The cytotoxic activity of a new hydrosoluble axysterol derivative, a phosphoric
      acid diester of 7 beta-hydroxycholesterol (7 beta-OHC, one of the most toxic
      oxysterol) and of galactose has been evaluated using cultured tumor cells of
      various origins, and compared with 7 beta-OHC. As its parent compound, XG-142
      exhibits a significant cytotoxic activity against all the cell lines tested, but
      the IC50's were higher than those obtained with 7 beta-OHC. Moreover, the
      cytotoxicity was slower to appear than after a 7 beta-OHC treatment. Cell phase
      distribution was analysed, and revealed some differences between the two
      compounds. Both oxysterols induced apoptosis at micromolar concentrations, as
      evidenced by several methods including agarose gel electrophoresis of fragmented
      DNA and flow cytometry of propidium iodide labeled cells. Apoptosis was also
      obtained when 7 beta-OHC and XG-142 were combined at concentrations unable to
      induce this type of cell death when used separately. Upon normal murine spleen
      cells, XG-142 was found to be less toxic than 7 beta-OHC, and the capacity to
      respond to Con A stimulation was preserved. Therefore, XG-142 can be considered
      as a promising soluble analogue of 7 beta-OHC, and its application as anticancer
      agent should be considered.

PMID- 9252693
TI  - Tyrosine kinase expression profile in bladder cancer.
AB  - The expression pattern of tyrosine kinase in bladder cancer cells was evaluated
      by PCR amplification with degenerate primers derived from conserved catalytic
      domain in tyrosine kinase. The results indicated that TRK-E and Arg kinases were
      more abundantly expressed than several other kinases in bladder cancer. In
      addition, we identified a novel clone whose sequence could not be matched in
      GeneBank. This clone may represent a serine/threonine kinase based on sequence
      similarity.

PMID- 9252692
TI  - MDA468 growth inhibition by EGF is associated with the induction of the cyclin
      dependent kinase inhibitor p21WAF1.
AB  - Epidermal growth factor (EGF) usually stimulates the proliferation of a variety
      of normal and malignant cells. In contrast, MDA468, a human breast cancer cell
      line with a very high number of EGF receptors, is growth inhibited in response to
      concentrations of EGF that stimulate most other cells. The purpose of this study
      was to elucidate the cellular mechanisms involved in EGF-induced growth
      inhibition. EGF treatment stimulated the sustained expression of the cyclin
      dependent kinase (CDK) inhibitor p21WAF1. The p21WAF1 induction in EGF-treated
      MDA468 cells is probably p53-independent since these cells contain no active p53.
      The promoter for p21WAF1 gene contains binding sites for signal transducer and
      activator of transcription (STAT) and EGF is known to activate members of this
      family of transcription factors. Using electrophoretic mobility shift assays
      (EMSA), we found that EGF activates STAT1 and STAT3 in the MDA468 cells. These
      activated STATs specifically recognized the three conserved STAT-responsive
      elements in the p21WAF1 gene promoter, suggesting that STATs may be responsible
      for the p21WAF1 induction by EGF in MDA468 cells. The sustained rise in p21WAF1
      in response to EGF is proposed to be a means of growth inhibition in these cells.

PMID- 9252694
TI  - Detection of rare human breast cancer cells. Comparison of an immunomagnetic
      separation method with immunocytochemistry and RT-PCR.
AB  - BACKGROUND: The detection of occult carcinoma cells in patients with breast
      cancer may aid determination of prognosis and the development of new therapeutic
      approaches. In this study, we report a new method to detect rare human breast
      cancer cells, which combines an immunomagnetic separation (IMS) procedure with
      cytokeratin 19 (CK 19) immunostaining. MATERIALS AND METHODS: Four monoclonal
      antibodies (MAb) previously characterized against cell surface antigens (1BE12,
      ED8, 7B10 and 83D4), were evaluated for IMS optimization. Immunoseparated
      epithelial cells were identified using a MAb against CK 19. We compared the IMS
      procedure with the immunocytochemistry (ICC) and the RT-PCR for CK 19 on an "in
      vitro" experimental model. RESULTS: The best results in IMS procedures were
      obtained using MAbs 1BE12 (directed against Lewis y antigen) and ED8 (directed
      against MUC 1). In reconstitution experiments, using several ratios of T47D cells
      mixed with peripheral-blood mononuclear (PBMN) cells, the IMS procedure reliably
      detects one mammary carcinoma cell in 5 x 10(5) PBMN cells, whereas the ICC
      detects up to one T47D cell per 10(5) PBMN cells. The best sensitivity was
      observed with the RT-PCR (up to one T47D cell per 10(6) PBMN cells). We found the
      same high specificity with the three methods evaluated. CONCLUSIONS: The IMS
      procedure using MAbs 1BE12 or ED8 associated with CK 19 immunostaining is a
      specific, sensitive, and feasible method for the detection of rare human breast
      cancer cells. This method proved to be better than the ICC staining but its
      sensitivity was lower than that of RT-PCR for CK 19.

PMID- 9252695
TI  - HNPCC-Lynch syndrome and idiopathic inflammatory bowel disease. A hypothesis on
      sharing of genes.
AB  - Colon cancer occurring in patients with Lynch Syndrome and in Inflammatory Bowel
      Disease (IBD) share many features. There is some evidence to support the
      assumption that multiple genetic factors play an important role in the
      pathogenesis of idiopathic IBD and Lynch Syndrome. In our previous study,
      providing detailed medical, genetic and pathologic findings on 202 hereditary non
      polyposis colorectal cancer (HNPCC) relatives we found in the colonic mucosa
      features indicating an IBD though all the screened subjects of the family denied
      symptoms of IBD. Some studies have reported that the rate of undetected IBD
      ranges from 27 to 38%. Finally, a member of this family, considered not at risk
      for cancer by genetic analysis results, developed a clinically manifested IBD.
      The morphological aspects of the disease were not discussed in our previous
      study. It is possible that many members of this family inherit a major gene
      giving liability to the disease and are carriers of a subclinical form of IBD
      with a minimal morphological marker which becomes manifest in some members when
      other factors intervene. A possible genetic model linking the two diseases can be
      suggested: IBD needs two major genes for susceptibility (s) and clinical
      development (D). Both can be present in IBD and Lynch Syndrome, but in the latter
      a third gene plays a suppressor role on the development gene (D). In conclusion,
      we hypothesize that the IBD developing gene may be considered as protective
      against HNPCC, and this condition may result in a selective genetic advantage.

PMID- 9252696
TI  - Immunohistochemical detection of cathepsin D in low grade breast invasive cancer.
AB  - BACKGROUND: Cathepsin D (CatD) can facilitate the invasive behaviour of breast
      cancer cells and thus plays a key role in the mechanism of invasion and
      metastasis. MATERIALS AND METHOD: The expression of the protease CatD was
      evaluated using an immunohistochemical technique with a polyclonal antibody on
      paraffin-embedded tissue from 80 women treated for invasive ductal mammary
      carcinoma not otherwise specified (NOS). RESULTS: Thirty seven tumours (46%)
      showed prominent staining of cells in the tumour. Neoplastic cell staining for
      CatD correlated with axillary nodal involvement (p < 0.05), high oestrogen
      receptor positivity status (p < 0.01) and low or moderate tumour grade (p <
      0.05). Stromal cell (primarily histiocyte) CatD immunostaining was frequently
      noticed and was proportional to the degree of the intratumoural inflammatory
      infiltrate. CONCLUSIONS: Cat D detection in neoplastic cells is likely to be
      involved in the invasive capability of well differentiated breast cancer cells,
      but it may simultaneously reflect the functional integrity of the oestrogen
      response pathway, commonly observed in well-differentiated tumours.

PMID- 9252697
TI  - Prognostic influence of blood transfusion on minimal residual disease in resected
      gastric cancer patients.
AB  - BACKGROUND: The effect of blood transfusion on prognosis of resected cancer
      patients has been debated controversially. Therefore, we raised the hypothesis
      that transfusion-associated immunomodulation affects minimal residual disease
      after curative tumour resection, an unknown and uncontrolled phenomenon in all
      former studies which might significantly influence long-term prognosis. PATIENTS
      AND METHODS: 104 patients of a prospective study with curatively resected gastric
      cancer were stratified according to the immunocytochemical detection of
      disseminated tumour cells in bone marrow and the prognostic impact of allogeneic
      blood transfusion was tested. Multiple sequential bone marrow aspirations during
      follow-up were performed in 74 patients to investigate the blood transfusion
      effect on long-term development of this systemic disease component. RESULTS:
      Whereas in patients with tumour cell detection in bone marrow a significant
      association of blood transfusion and survival was seen (P = 0.048; relative risk
      2.91; 95% CI 1.51-5.61), this was not found in patients without disseminated
      tumour cells (P = 0.129). Quantitative development of tumour cells in bone marrow
      during follow-up demonstrated a significant quantitative increase of tumour cells
      in transfused patients only (P = 0.028). CONCLUSION: These findings might explain
      the contradictory results of recent studies and suggest that the prognostic
      effect of transfusion is mediated through an impact on minimal residual disease
      in resected cancer patients.

PMID- 9252698
TI  - Is p53 expression, detected by immunohistochemistry, an important parameter of
      response to treatment in testis cancer?
AB  - BACKGROUND: Several prior studies revealed positive p53 expression via
      immunohistochemistry (IHC) in a large percentage of germ cell testicular cancers
      (GCTTs). However, the predicting and prognostic value of this protein remains to
      be defined. Therefore, the aim of our study was to further clarify the role of
      p53 protein in GCTTs and to look for correlations between its gene expression and
      other disease parameters, including histological subtype, stage and clinical
      resistance sensitivity. Furthermore, we correlated p53 protein expression with
      that of MDRI gene product protein (Pgp) in order to examine the interrelationship
      between these two markers. PATIENTS AND METHODS: 77 untreated patients with GCTTs
      were investigated for their p53 expression using monoclonal antibody and
      immunohistochemistry in paraffin-embedded specimens. There were 34 patients with
      stage I, 16 with stage II, 27 with stage III disease. RESULTS: All tumor types,
      except differentiated teratomas, were immunoreactive for p53 to a various extent
      ranging from scarcely positive to homogeneously stained tumor cells. Seminomas
      (S) and embryonal carcinoma (EC) components showed the most positive nuclear
      staining. p53 expression showed a significant inverse correlation with the stage
      of disease (P < 0.0003). There was a significant positive relationship between
      p53 immunoreactivity and response to treatment (P = 0.0012), i.e. high levels of
      p53 expression correlated with clinical sensitivity of the tumors to
      chemotherapy. We could demonstrate a statistically significant opposite
      relationship between p53 and Pgp immunoreactivity (P < 0.0005). CONCLUSION: Our
      results show that p53 status in tumor cells may be a strong determinate of
      susceptibility to chemotherapy and that p53 overexpression has a favorable
      prognosis in terms of response to treatment in GCTTs. Moreover, the findings
      provide clinical evidence for the presense of significant relationship between
      p53 and MDR1/Pgp immunoreactivity. They also suggest that patients resistant to
      chemotherapy and lacking p53 expression might benefit from an alternative
      appropriately designed chemotherapeutic regimen to achieve further successful
      treatment in GCTTs.

PMID- 9252699
TI  - Malignant myoepithelioma of the minor salivary glands arising in a pleomorphic
      adenoma.
AB  - This paper reports a case of carcinoma expleomorphic adenoma of the minor
      salivary glands, where the carcinomatous component was a malignant myoepithelioma
      (myoepithelial carcinoma). Immunohistochemical investigation showed that the
      carcinoma cells were positive for cytokeratin, S-100 protein and vimentin, and
      focally positive for actin and desmin. A moderate level of positivity was found
      fo laminin and collagen IV around the neoplastic islands. These data are the
      confirmation that the carcinoma cells were myoepithelial. The number of mitoses,
      the istotype, the minimal extent of extracapsular infiltration and the absence of
      vascular invasion made it possible to include this particular case among those
      with a better prognosis.

PMID- 9252700
TI  - Prognostic significance of Hsp-27 in astrocytic brain tumors: an
      immunohistochemical study.
AB  - Formalin-fixed paraffin-embedded tumor specimens from 95 patients with
      supratentorial astrocytic brain tumors were immunostained by a monoclonal
      antibody against the heat shock protein-27 (Hsp-27) using the
      streptavidin/peroxidase method. The immunohistochemical analysis was scored in a
      semiquantitative fashion incorporating both the intensity and distribution of
      specific staining (score): the immunohistochemical results were correlated with
      the histological grade of the tumors and patients' sex and age. Furthermore, Hsp
      27 expression was studied in two groups into which the patients were further
      divided: group (a) previously untreated patients (n = 76) whose biopsy or
      surgical resection was related to their initial presentation and diagnosis and
      group (b) patients (n = 19) with reccurent disease who underwent radiotherapy
      and/or chemotherapy. Strong Hsp-27 cytoplasmic immunopositivity was observed in
      42 out of 51 (82%) glioblastomas, in 8 out of 20 (40%) anaplastic astrocytomas
      and in 2 out of 24 (8%) astrocytomas. The mean Hsp-27 score was 45.2 in
      glioblastomas, 6.5 in anaplastic astrocytomas and 0.4 in astrocytomas. The
      expression of Hsp-27 immunoreactivity appeared to be independent of the age and
      sex of the patients. A non significant difference was defined between untreated
      patients and previously treated patients. Hsp-27 immunoreactivity was observed in
      the microvascular endothelial proliferations and in tumor blood vessels. Normal
      astrocytes were Hsp-27 negative. These findings indicate that, in contrast with
      the low Hsp-27 expression found in benign astrocytomas, the expression of Hsp-27
      in a number of poorly differentiated tumors, including glioblastomas and
      anaplastic astrocytomas, is consistent and independent of previous treatment of
      the patients. We support the involvement of Hsp-27 in the growth of astrocytic
      brain tumors.

PMID- 9252701
TI  - Esthesioneuroblastoma: a general review of the cases published since the
      discovery of the tumour in 1924.
AB  - Esthesioneuroblastoma (ENB) arises from the neuroepithelium in the olfactory rim
      of the nasal cavity. It accounts for about 3% of all intranasal tumours. Reviews
      since the first description by Berger and Luc in 1924 never reported more than a
      hundred cases, stressing the rarity of the tumour. However, a thorough literature
      review revealed a total of 945 reported cases. In our search we found a total of
      1,457 cases chronicled in the literature of which perhaps 487 were cited in more
      than one paper, bringing the total of reported cases to 945. Author cases
      accounted for 198 and therefore collaborative efforts accounted for 747 cases.
      Sex distribution was 53.36% male and 46.64% female. Kadish classification was
      applied to 553 cases revealing 103 (18.29%) class A cases, 182 (32.33%) class B
      and 278 (49.38%) class C cases. This distribution was generally stable through
      the decades. Treatment could be classified in 898 cases. It consisted of surgery
      alone in 25.17% (226 cases), radiotherapy alone in 18.37% (165 cases), combined
      surgery and radiotherapy in 43.21% (388 cases) and chemotherapy in 13.2% (119
      cases), followed in 11 cases (1.22%) by bone marrow transplant. In the reported
      cases an overall follow up could be evaluated in 477 cases, while in only 234
      cases a five-year follow up was done. The outcome was 68.38% alive and disease
      free, 12.82% alive with disease and 18.80% dead. From these 20.51% had surgery
      only, 11.11% radiotherapy and 68.38% combined surgery and radiotherapy. The best
      survival rates were obtained by combined therapy (72.5% vs. 62.5% surgery alone
      and 53.85% radiotherapy alone). Death rates were highest after radiotherapy alone
      (30.77% versus 18.75% in combined therapy and 12.50% after surgery alone). In
      conclusion, ENB is a rare but not exceptional tumour. It is best treated with
      combined surgery and radiotherapy. Unfortunately early diagnosis is still
      uncommon and no significant changes to the proportions of Kadish classes at first
      diagnosis have been noted in recent decades. A greater awareness of the tumour
      and earlier diagnosis seems the major focus for future research.

PMID- 9252702
TI  - Differential cancer morbidity towards year 2000 in a population disease outlook
      across Europe. II. The male gender.
AB  - The conception of new, 'avoidable' life style diseases in affluent Western
      societies is largely based upon observations in groups of middle-aged urban males
      with mortality as the major end-point. This applies to cancer, too, and studies
      of morbidity, where cancer is put within the overall disease spectrum, are called
      for as a necessary intermediary stage for hypothesis generation and initiation of
      evaluative and interventive epidemiological projects in the community. Here also
      the conditions and circumstances that determine health and well being, that is,
      salutogenetic factors, come increasingly into focus. We made a comparative
      analysis of the total hospitalization for somatic diseases during 1986-1987 at
      the Linkoping University Hospital in the county of Ostergotland, Sweden and the
      both complementary and commensurable Heraklion University Hospital on Crete. They
      are representative of their respective European situations, and are the only
      somatic hospitals in their regions. Large differences were found with lower
      morbidity in the more 'Arcadian', rural settings. The results provide valuable
      data on traits and patterns between earlier surveys such as the Seven Countries
      study and today. We have earlier reported on the findings from the female group
      of the two populations, and here wish to concentrate on the males. In particular,
      cancer is compared with the both prominent and 'archetypical' forms of male ill
      health that are comprised by cardiovascular diseases and accidents. We discuss
      some of the salutogenetic as well as pathogenetic factors that call for closer
      study in the next stage of our project, whose emblem of Ariadne's thread we feel
      also has a strong bearing on the masculine gender.

PMID- 9252703
TI  - Advanced colorectal cancer, refractory to infusional fluorouracil treatment:
      efficacy of second line fluorouracil in combination with a different biochemical
      modulation.
AB  - BACKGROUND: Currently there is no standard second line treatment for patients
      with advanced colorectal cancer (ACC). Previous reports have demonstrated that
      some patients may benefit from second line infusional 5-fluorouracil (5-FU) after
      failing 5-FU bolus treatment. PATIENTS AND METHODS: We retrospectively studied
      the efficacy and toxicity of infusional 5FU regimens given in second line, which
      only differed from the first line regimen in the type of biochemical modulation
      and compared these results in a non-randomized fashion to the outcome of patients
      receiving supportive care only in second line. RESULTS: Sixty six patients with
      ACC were treated in first line with an infusional 5-FU-based schedule. At the
      time of disease progression 38 patients received supportive care only. The
      remaining 28 patients continued treatment with the same 5-FU regimen, but with
      another biochemical modulator. Fourteen patients achieved stable disease for a
      median duration of 6 months and one patient achieved a complete remission which
      lasted 34 months. The median survival from the time of disease progression on
      first line treatment was 7 months for patients who received second line
      treatment, whereas those who received supportive care survived for a median
      period of 3 months (p < 0.05). CONCLUSION: Changing the type of biochemical
      modulation of infusional 5-FU as a second line treatment-alternative may be of
      some benefit to a subgroup of patients with ACC.

PMID- 9252704
TI  - Atypical mitoses in colectomy specimens from patients with long standing
      ulcerative colitis.
AB  - About 1% of dividing epithelial cells in esophageal, gastric and duodenal mucosas
      with chronic inflammation have been found to be atypical. In the present work,
      the characteristics of the mitotic figures in the colorectal mucosa with
      ulcerative colitis (UC)--a disease characterized by chronic mucosal inflammation-
      were investigated. Feulgen-stained histologic sections (having > 30 mitoses in 3
      large tissue sections) from 59 colectomy specimens with long standing total UC
      were scrutinized at high power microscopy (1000 x). A total of 2,104 mitoses were
      recorded in the 59 specimens with UC: 591 (28.1%) were atypical. Atypical mitoses
      were present in 19.2% (SE 4.7) of the 26 specimens having chronic active
      inflammation, in 16.9% (SE 5.6) of the 9 with UC in remission, in 34.6% (SE 7.7)
      in mucosas with dysplasia (n = 8) and in 49.1% (SE 10.2) in carcinoma (n = 16).
      Atypical mitoses were also found in 17.0% (SE 5.4) in the non-dysplastic mucosa
      from colitic patients having dysplasia or carcinoma elsewhere as well as in 0.96%
      (SE 0.3) in 14 "noncolitic" controls with chronic inflammation. The percentage of
      atypical mitoses was influenced-except in areas with dysplasia or carcinoma-by
      the duration of the disease (< 15 or > 16 years), but not by the age or the
      gender of the patients. Since the frequency of atypical mitoses in "noncolitic"
      controls with chronic inflammation was low, it is evident that factors other than
      chronic inflammation may be involved in the induction of atypical mitoses in
      colitics. Acquired nuclear aberrations detected during the mitotic phase, but not
      at interphase do occur in colorectal epithelial cells from long-standing UC
      patients, not only in areas with dysplasia or carcinoma but also in areas without
      those neoplastic changes.

PMID- 9252705
TI  - Pharmacokinetics of 5-fluorouracil (5-FUra) in patients with metastatic
      colorectal cancer receiving 5-FUra bolus plus continuous infusion with high dose
      folinic acid (LV5FU2).
AB  - The pharmacokinetics of 5-fluorouracil (5-FUra) were investigated in 16 patients
      with metastatic colorectal cancer receiving high-dose folinic acid (LV 200 mg/m2)
      followed by 5-FUra bolus (400 mg/m2) and continuous infusion (600 mg/m2) on days
      1 and 2. Quantitation of unchanged drug was assessed by a highly specific high
      performance liquid chromatographic method. The concentrations of 5-FUra at the
      end of the loading dose averaged 30.7 +/- 13.2 micrograms/ml (i.e., 236 microM).
      The steady-state plasma concentration averaged 0.31 +/- 0.11 microgram/ml (i.e.,
      2.4 microM). 5-FUra plasma levels declined rapidly after the end of infusion with
      an apparent elimination half-life of 7.08 +/- 3.21 minutes. Clearance ranged from
      776 to 3023 ml/min/m2. Large patient-to-patient variations in plasma 5-FUra
      concentrations were observed. No toxicity greater than WHO grade 2 was seen. One
      patient experienced grade 1 stomatitis and two others experienced grade 1 and 2
      myelosuppression. One patient developed diarrhoea and another suffered asthenia.
      Nausea and vomiting were observed in 5 patients.

PMID- 9252706
TI  - Tumor marker concentrations in normal and malignant tissues of colorectal cancer
      patients and their prognostic relevance.
AB  - Tumor markers CEA, CA19-9, CA15-3, CA125, AFP, beta-HCG, SCC were measured
      quantitatively in serum, tumor tissue and healthy colonic mucosa of patients with
      colorectal cancer. We wanted to investigate whether there is a difference in
      concentration between patients with and without recurrence of cancer. During the
      follow-up period 14 of 38 patients showed tumor recurrence. Patients with cancer
      relapse had higher preoperative serum levels of CEA and CA19-9 and significantly
      higher concentrations in their histologically normal colonic mucosa of CEA, CA19
      9, SCC and lower ones of CA15-3. The highest values of CEA, CA19-9, and SCC
      occurred in the mucosa of patients developing local cancer recurrence. Marker
      concentrations in tumor tissues themselves did not differ between patients with
      or without tumor relapse. Though this should be confirmed in a larger number of
      cases we conclude from these results that tumor marker concentrations in healthy
      colonic mucosa of patients with colorectal cancer may become valuable indicators
      of the risk of tumor recurrence.

PMID- 9252707
TI  - Prediction of nodal metastasis and prognosis in breast cancer: a neural model.
AB  - BACKGROUND: An increasing number of women with breast cancer are detected with
      the disease at an early stage, when the lymph nodes are not involved. In order to
      obviate the necessity to carry out axillary dissection, accurate surrogates for
      lymph node involvement need to be identified. In this paper we have examined the
      use of a neural network to predict nodal involvement. The neural approach has
      also been extended to investigate its predictive applicability to the long-term
      prognosis of patients with breast cancer. A number of established and
      experimental prognostic markers have been studied in an attempt to accurately
      predict patient outcome 72 months after first examination. METHODS: 81,
      unselected patients, presenting clinically, who had all undergone mastectomy for
      invasive breast carcinoma were considered in this study. A total of 12 markers
      were analysed for the prediction of lymph node metastasis, while node status
      itself was used as an additional marker for the prognostic analysis. In this case
      the outcome related to whether a patient had relapsed within 72 months of
      diagnosis. In both cases, a number of marker combinations were analysed
      separately in an attempt to classify those most favourable marker interactions
      with respect to lymph node prediction and prognosis. Patients were randomly
      divided into a training set (n = 50) and a test set (n = 31). The simulation was
      developed using the NeuralWorks Professional II/Plus software (NeuralWare,
      Pittsburgh, Pa, USA). RESULTS: In the case of lymph node metastasis, the neural
      network was able to correctly predict axillary involvement, or otherwise, in 84%
      of the patients in the test set by considering 9 of the 12 available markers.
      This represents an improvement of 10% over the traditional approach which
      considers the tumour grade and size only. The sensitivity and specificity were
      also shown to be 73% and 90%, respectively. With regard to patient prognosis,
      again 84% classification accuracy was obtained using a subset of the markers,
      with a sensitivity of 50% and a specificity of 96%. CONCLUSIONS: Although this
      study considered a relatively small sample of patients, nevertheless it
      demonstrates that artificial neural networks are capable of providing strong
      indicators for predicting lymph node involvement. There is no longer a need for
      axillary dissection with all its implications in patient morbidity and demands on
      clinical resources. The management of breast cancer and the planning of
      strategies for adjuvant treatments is also facilitated by the use of neural
      networks for the long-term prognosis of patients.

PMID- 9252708
TI  - Detection of occult liver metastases in colorectal cancer by measurement of
      biliary carcinoembryonic antigen.
AB  - About a 20-25% of the patients at diagnosis of colorectal carcinoma present with
      occult liver metastases. The aim of this work was to determine the prognostic
      significance of CEA bile level for the early detection of occult metastases. We
      determined the CEA blood level and the CEA bile level in 182 patients with
      colorectal carcinoma (3 Dukes' stage A, 86 Dukes' stage B, 53 Dukes' stage C, and
      40 patients with liver metastases) and also in 42 patients with simple
      cholelithiasis, as the control group. In the patients with cholelithiasis, the
      mean values of CEA serum and bile levels were normal. In patients with colorectal
      carcinomas the CEA serum levels ranged from 3 to 110 ng/ml, and the CEA bile
      level from 3 to 226 ng/ml. Patients with liver metastases, had a mean CEA serum
      level of 193 ng/ml, while CEA bile level was 1,225 ng/ml. In conclusion, our
      results suggest that the determination of CEA bile is highly useful in the
      diagnosis of occult liver metastases.

PMID- 9252709
TI  - Immunohistochemical detection of Glut3 in human tumors and normal tissues.
AB  - Malignant cells have been shown to utilize more glucose than normal cells in
      vitro and in vivo. Glut3 is a member of the facilitative glucose transporters
      family of transmembrane proteins, and its mRNA levels has been found to be
      elevated in human cancers, indicating that it may play a role in glucose uptake
      by cancer cells. Localization and extent of expression of Glut3 protein in normal
      and malignant human tissues is still largely unknown. We studied Glut3 expression
      in a series of 325 benign and malignant human tissues using standard
      immunoperoxidase technique. Of the normal tissues tested, Glut3 immunoreactivity
      was detected only in normal testis and placenta. Twelve of 14 (86%) testicular, 3
      of 22 (16%) ovarian, 2 of 8 (25%) gastric, and 11 of 41 (27%) non-small cell lung
      carcinomas were positive for Glut3. Other carcinomas, including those of the
      breast and colon, were negative. Only in Glut3-positive testicular carcinomas
      were most tumor cells Glut3-positive. We conclude that a) Glut3 has a limited
      expression in normal and malignant human tissues, as determined by
      immunohistochemical staining, b) Glut3 may play a role in glucose uptake in a
      subset of carcinomas of the lung stomach and ovary, and, therefore, these tumors
      may have a distinct clinical behavior, and c) Glut3 may be an attractive target
      for monoclonal therapy or imaging of testicular germ cell tumors.

PMID- 9252710
TI  - Lentinan potentiates immunity and prolongs the survival time of some patients.
AB  - For the selection of patients responding well to lentinan, we performed two
      immunological analysis of patients. Flow cytometric analysis was obtained from
      peripheral blood lymphocytes; the patients who had greater than 2.5 ratio of
      [CD11(-) CD8(+)/CD11(+) CD8(+) after treatment]/[CD11(-) CD8(+)/CD11(+) CD8(+)
      before treatment] at 10 days after lentinan administration showed prolonged
      survival. The analysis of the- levels of soluble factors such as IL-6, sIL-6R,
      TNF-alpha, G-CSF, sICAM-1, IAP, and PGE2 and the decreasing levels of G-CSF, IL
      6, and PGE2 after lentinan administration had a statistically significant
      correlation with the ratio of [CD4(+) CD29(+)/CD4(+) CD29(-) after
      treatment]/[(CD4(+) CD29(+)/CD4(+)CD29(-) before treatment]. The decrease in IL
      6, G-CSF, and PGE2 levels after lentinan administration indicated an increase in
      immunine potential. From these results, we belive that patients with over 2.5
      fold increase in [CD11(-) CD8(+)/CD11(+) CD8(+) after treatment]/[CD11(-)
      CD8(+)/CD11(+) CD8(+) before treatment] and showing a decrease in IL-6, G-CSF,
      and PGE2 levels after lentinan administration should continue treatment with
      lentinan for a long period.

PMID- 9252711
TI  - Chemosensitivity of anaplastic thyroid carcinoma and poorly differentiated
      thyroid carcinoma.
AB  - BACKGROUND: The prognosis of anaplastic thyroid carcinoma (ATC) and poorly
      differentiated thyroid carcinoma (PDTC) is very poor because of their resistance
      to chemotherapy. MATERIALS AND METHODS: We retrospectively evaluated the response
      to chemotherapy of 14 patients with ATC and examined the in vitro
      chemosensitivity of primary cultures of one ATC and five PDTCs from six recent
      patients. RESULTS: As assessed at one month after treatment, one patient had a
      partial remission (PR), 3 had no change (NC), and the other 10 progressed (PD).
      The mean survival of all 14 patients was 3.4 months (PD; 2.3 months, PR or NC; 6
      months). Five of the tumors (one ATC and four PDTCs) were resistant to all drugs
      examined: adriamycin, cisplatin, cyclophosphamide, etoposide, and carboplatin;
      cells from one PDTC were sensitive to adriamycin alone. Although five patients
      had administration of anti-cancer agents, none showed a response to chemotherapy.
      CONCLUSION: most ATCs and PDTCs are very resistant to anti-cancer agents. In
      vitro chemosensitivity testing may prevent the administration of ineffective
      chemotherapy.

PMID- 9252712
TI  - Prognostic factors in metastatic breast cancer patients obtaining objective
      response or disease stabilization after first-line chemotherapy with epirubicin.
      Evidence for a positive effect of maintenance hormonal therapy on overall
      survival.
AB  - Randomized trials suggest that the outcome of metastatic breast cancer (BC)
      patients is not affected by the currently available therapies. Although response
      rates per se may be associated with survival prolongation, patients experiencing
      objective response may be those patients fated to have the longest natural
      disease history. The separation of responders from progressing patients after
      first-line chemotherapy could allow the selection of a more homogeneous subgroup
      in which further treatment strategies might achieve a better control of the
      disease. This study investigated the influence of some patient characteristics,
      disease characteristics, and previous treatments on the outcome of non
      progressing patients after first-line chemotherapy with epirubicin
      administration. We also evaluated the effect of the maintenance endocrine therapy
      in improving response rate and overall survival (OS). From May 91 to May 93, 207
      patients were enrolled in a randomized trial aiming to compare the activity of
      epirubicin (120 mg/sqm) +/- lonidamine (600 mg/daily). Among the 169 patients
      attaining complete (CR), partial response (PR) or disease stabilization (SD), 65
      were not randomly submitted to maintenance endocrine therapy (MET). Liver
      involvement, previous adjuvant chemotherapy and previous hormonal therapy
      (administered in adjuvant setting or for advanced disease) were found to
      negatively influence OS both in univariate and multivariate analysis. Differences
      in OS stratifying patients according to DFI, estrogen receptor status and PS did
      not attain statistical significance. Patients receiving MET survived
      significantly longer than those submitted to observation and this difference
      maintained the statistical significance also within patient subsets homogeneous
      for specific prognostic features. In conclusion, most prognostic factors for
      advanced BC have been confirmed in our series of patients obtaining CR, PR or SD
      to full dose epirubicin. The positive prognostic impact of MET is impressive and
      deserves confirmation in randomized studies.

PMID- 9252713
TI  - Long-term survivors of non-small cell lung cancer after radiation therapy: the
      significance of histological type.
AB  - To determine if histological type was a prognostic factor for non-small cell lung
      cancer (NSCLC), 67 two-year survivors were analyzed retrospectively after
      definitive radiation therapy (RT) for inoperable or unresectable Stage I-III
      NSCLC. There was no difference in short-term outcome (within 2 years) between
      patients with squamous cell carcinoma and patients with adenocarcinoma. After 2
      years, the 5-year survival rate for the 2-year survivors was 56% for squamous
      cell carcinoma (n = 55) and 34% for adenocarcinoma (n = 12). According to degree
      of histologic differentiation, patients with poorly differentiated adenocarcinoma
      had a poorer outcome compared than those with well differentiated adenocarcinoma
      and squamous cell carcinoma as a whole. Among progression-free patients at the
      end of 2 years, 97% of patients with squamous cell carcinoma survived without
      evidence of disease for more than 5 years. Disease-free 2-year survival should be
      substituted for 5-year survival in patients with squamous cell carcinoma treated
      with RT.

PMID- 9252714
TI  - Defibrotide in the prevention of venous irritation by vinorelbine administration.
AB  - BACKGROUND: Vinorelbine is active in a variety of malignancies. The most common
      side effects are leukopenia and granulocytopenia, moreover Vinorelbine is a
      vescicant and venous irritant, the incidence of the latter being 10-26% in
      patients who received VNB as a 20-30 minute peripheral infusion. To prevent
      venous toxicity we have carried out a study in order to evaluate the efficacy of
      Defibrotide in this issue. MATERIALS AND METHODS: 41 patients were enrolled in
      the study, the experimental schedule was: Defibrotide 400 mg on 250 cc of normal
      saline iv, after 15 minutes of infusion, we delivered quick, brief and repeated
      pulses of Vinorelbine through the plastic tube followed by remaining Defibrotide:
      For grading venous irritation we used the scale by Rittenberg et al. RESULTS: A
      total of 360 infusion were delivered, the incidence of any venous irritation was
      5% and maximum grade 2. No severe toxicity was recorded. CONCLUSION: These data
      show that Defibrotide might serve as a therapeutic drug to prevent vascular
      toxicity by Vinorelbine.

PMID- 9252715
TI  - p53 protein expression as prognostic factor in human pancreatic cancer.
AB  - Mutations in the p53 tumor suppressor gene are considered to play an important
      role in the carcinogenesis of pancreatic cancer. The present study was designed
      to assess the clinicopathological significance of the expression of p53 protein
      in human pancreatic cancer. A total of 64 specimens of pancreatic cancer (44
      primary and 20 metastatic lesions) were obtained by surgery in our department
      between 1982 and 1995, and p53 protein was stained using an immunohistochemical
      staining method (strepto-avidin-biotin complex method) with 2 kinds of anti-p53
      monoclonal antibodies (DO-1 and PAb240). DO-1-p53 was usually stained in the
      nucleus of cancer cells and was positively expressed in 35 out of 64 specimens
      (54.7%): 21 out of 44 primary lesions (47.7%), and 14 out of 20 metastatic
      lesions (70.0%). On the other hand, PAb240-p53 was stained in both the nucleus
      and cytoplasm in 45 out of 64 specimens (70.3%): 33 out of 44 primary lesions
      (75.0%) and 12 out of 20 metastatic lesions (60.0%). The survival rate of the
      patients with DO-1-p53 (+) pancreatic cancer after pancreatectomy was
      significantly lower than that of patients with DO-1-p53 (-) pancreatic cancer. On
      the other hand, there were no significant implications of PAb240-p53 protein
      expression on survival after pancreatectomy. With regard to the
      clinicopathological characteristics, the rate of DO-1-p53 protein expression was
      significantly higher in elderly patients (> or = 65 y.o.). As a result, DO-1-p53
      protein expression may be a beneficial prognostic factor for patients with
      pancreatic cancer, and it is a factor independent of the stage and other
      clinicopathological factors.

PMID- 9252716
TI  - Prognostic significance of proliferating cell nuclear antigen expression in
      transitional cell carcinoma of the upper urinary tract.
AB  - BACKGROUND: Haphazard cell proliferation is a fundamental biologic defect in
      cancer. Thus, assessment of the growth fraction provides a valuable index of
      biological property for human neoplasm. Proliferating cell nuclear antigen (PCNA)
      expression has been used to estimate the growth fraction of human cancer, and its
      prognostic value. Information in transitional cell carcinoma (TCC) of the upper
      urinary tract, however, is very few. MATERIALS AND METHODS: A total of 73
      patients with TCC of the upper urinary tract was collected between July 1988 and
      December 1995 for this study. The labeling index of PCNA immunostaining was
      correlated with clinicopathologic factors and compared for its prognostic value
      with a median follow-up of 54 months. RESULTS: The PCNA index was positively
      associated with histological grading, tumor stage and patient prognosis (P =
      0.00, respectively). Multivariate analysis demonstrated that significant factors
      in relation to patient survival were tumor stage (P = 0.01), followed by PCNA
      index (P = 0.04) and gender of patients (P = 0.04). Multiple comparison revealed
      that PCNA index set at 0.30 had prognostic value in terms of patient survival (P
      = 0.00), and the risk of metachronous bladder recurrence (P = 0.02). CONCLUSION:
      Our data suggested that assessment of PCNA index may be used as an adjuvant
      prognostic factor for patients with TCC of the upper urinary tract.

PMID- 9252717
TI  - Feasibility and toxicity of combination chemotherapy with ifosfamide,
      vinorelbine, cisplatin versus ifosfamide, vinorelbine in patients with advanced
      non small cell lung cancer.
AB  - Vinorelbine (VNB) and Ifosfamide (IFO) have recently been proposed for treatment
      of non small cell lung cancer (NSCLC). The two drugs separately induce response
      rates in excess of 20% and, when combined, of 32.56%. Cisplatin (DDP) is
      considered a standard in chemotherapy of NSCLC affected patients. We report data
      on the feasibility and the toxicity of an IFO, VNB and DDP combination in
      comparison with IFO, VNB association. Results obtained show that the IFO, VNB,
      DDP combination has a more severe toxicity profile than the IFO, VNB combination
      although not to a degree precluding its feasibility. Responses, however, appear
      somewhat more favorable than in the group treated with the combination IFO, VNB.
      It is therefore necessary to ascertain if clinical advantages in survival and
      symptom palliation offered by IFO, VNB, DDP combination outweigh impairment in
      quality of life due to its significant toxicity.

PMID- 9252718
TI  - Epidermal growth factor receptor-immunohistochemical detection and clinical
      significance for treatment of primary breast cancer.
AB  - Epidermal growth factor receptor is considered to play an important role in the
      carcinogenesis and progression of breast cancer, but its clinical significance
      remains controversial mainly due to different methods and methodical problems. We
      determined EGF-R expression by an immunohistochemical assay on paraffin-embedded
      primary breast cancer tissue by means of the anti EGF-R mab E30 (Merck, FRG) and
      streptavidin-peroxidase technique. Material and clinical data were available from
      111 patients with a mean follow-up time of 75.4 +/- 1.1 months (range 61-90
      months). 21 (18.9%) of the breast cancer specimens showed positive staining for
      EGF-R 5 year-overall survival in patients with EGF-R negative tumors was 61.7%
      compared with 41.6% of patients with EGF-R positive breast carcinomas. No
      correlation was found between the expression of EGF-R and other prognostic
      factors except an inverse relationship with the expression of the estrogen
      receptor (p < 0.05). Whereas EGF-R expression demonstrated prognostic
      significance in univariate analysis, this could not be confirmed by multivariate
      analysis. Immunohistochemical determination of EGF-R represents a reliable and
      simple method to obtain more data about the biological behavior of malignant
      breast disease with increasing impact on therapeutic procedures.

PMID- 9252719
TI  - Implications of serum basic fibroblast growth factor levels in chronic liver
      diseases and hepatocellular carcinoma.
AB  - Angiogenesis occurs in response to tissue damage, and is of vital importance for
      tumor growth and metastasis. Basic fibroblast growth factor (bFGF), a well-known
      angiogenic factor, has been suggested to be a useful diagnostic marker in certain
      hypervascular tumors. However, the relevance of its detection has not been well
      evaluated in patients with hepatocellular carcinoma (HCC) and benign chronic
      liver diseases. In the current study, immunoassay of bFGF was performed on serum
      samples from 39 patients with HCC, 21 with liver cirrhosis, 22 with chronic
      hepatitis and 40 normal subjects. The serum bFGF level was significantly
      increased in patients with liver cirrhosis and HCC when compared with those with
      chronic hepatitis or normal subjects (all p-values < 0.001). However, no
      difference was observed between the groups with liver cirrhosis and HCC (p >
      0.05). If we set 9.6 pg/ml (mean + 3 standard deviations of bFGF in the control
      group) as the upper limit of normal serum level of bFGF, elevated bFGF
      concentrations were noted in 9.1%, 42.9% and 51.3% of patients with chronic
      hepatitis, liver cirrhosis and HCC respectively. In non-cancer patients, the
      coexistence of acute illness (p = 0.000) was an independent factor related to the
      elevation of serum bFGF. On the other hand, a multivariate analysis demonstrated
      that both advanced stage of cancer (p = 0.026) and coexistence of acute illness
      (p = 0.000) influence the serum level of bFGF in patients with HCC. We conclude
      that serum bFGF levels are significantly higher in patients with HCC and are
      positively correlated with advanced tumor stage. Nevertheless, elevation of serum
      bFGF may also be observed in a significant number of patients with liver
      cirrhosis. Therefore, measurement of serum bFGF alone cannot be satisfactory as a
      tumor marker for diagnosis of HCC. In addition, it is important to point out that
      coexistence of acute illness may be a crucial confounding factor in the diagnosis
      or monitoring of any cancer by the estimation of serum bFGF.

PMID- 9252720
TI  - Vascular endothelial growth factor and its receptor correlate with angiogenesis
      and survival in pulmonary adenocarcinoma.
AB  - The vascular endothelial growth factor (VEGF) and its receptor (Flt) protein
      expression was immunologically studied individually and in combination with the
      microvascular density (MVD) determined by the factor 8-related antigen (F8RA) and
      their prognostic value in 118 patients with a pulmonary adenocarcinoma. The
      presence of VEGF and Flt was associated with the MVD and prognosis. A reduced
      expression of both of VEGF and Flt correlated with less tumor angiogenesis and a
      better prognosis. Our findings suggest that VEGF and Flt expressions play an
      important role in tumor angiogenesis and that the VEGF and Flt coexpression
      promotes angiogenesis and metastasis in pulmonary adenocarcinoma.

PMID- 9252721
TI  - HLA antigen as predictive index for the outcome of breast cancer patients with
      adjuvant immunochemotherapy with PSK.
AB  - We demonstrated that the prognosis of breast cancer patients who received
      adjuvant immunochemotherapy with Krestin (PSK) showed a tendency to be better
      than that of breast cancer patients receiving chemotherapy only. We
      retrospectively investigated the usefulness of HLA typing for selecting patients
      to receive adjuvant immuno-chemotherapy with PSK. One hundred and thirty-four
      patients with operable breast cancer were typed as HLA-A, -B, -C by a
      lymphocytotoxicity test. Patients without vascular invasion had no adjuvant
      therapy (NA group). Patients with vascular invasion in the tumor and/or in the
      metastatic lymph node were randomized into two groups. In group 1 (FEMP only), a
      combination chemotherapy of 100 mg of 5-fluorouracil (F), 50 mg of
      cyclophosphamide (E), 2 mg of mitomycin C (M), and 5 mg of predonisolone (P) was
      orally administered daily for 28 days (one course). In group 2 (FEMP+PSK), FEMP
      and 3.0 g of PSK were orally administered for 28 days (one course). Two courses a
      year of these agents were given for five years in both groups. Each group (NA,
      FEMP, FEMP+PSK) was stratified by the presence of HLA B40 type (B40(+)) or not
      (B40(-)). Five- and 10-year disease-free survival (DFS) rates (93%, 80%,
      respectively) of patients with B40(+) seemed to be better than those (83% and
      51%) of patients with B40(-). In the NA group, 5- and 10-year DFS were 100% and
      71% in patients with B40(+), 92% and 76% in those with B40(-), respectively. In
      the FEMP group (chemotherapy only), 5- and 10-year DFS of patients with B40(+)
      were both 84%. These were not statistically significant compared with those (82%
      and 33%) of patients with B40(-). On the other hand, in the FEMP+PSK group, 5-
      and 10-year DFS of patients with B40(+) were both 100%, and those of patients
      with B40(-) were 76% and 55%, respectively. DFS of patients with B40(+) was
      significantly better than that of patients with B40(-). It is concluded that HLA
      typing may be a predictive index in determining the use of immunochemotherapy
      combined with PSK for patients with operable breast cancer.

PMID- 9252722
TI  - Comparison of the long-term results of brachytherapy for T1-2N0 oral tongue
      cancer treated with Ir-192 and Ra-226.
AB  - BACKGROUND: The authors report the compatibility of iridium-192 (Ir-192) to
      Radium-226 (Ra-226) based on the clinical results of three-decades. METHODS: From
      1967 through 1985, 119 patients with early oral tongue cancer (T1-2N0) were
      treated with conventional Ra-226 needles and 135 patients with Ir-192 hair pins.
      RESULTS: Local control rates at 10 years for T1 and T2 tongue cancer were 79% and
      61% for patients treated with Ra-226, 83% and 68% with Ir-192. The 10-year cause
      specific survival rates for the T1 and T2 patients with Ra-226 were 76% and 63%,
      and those with Ir-192 were 77% and 68%, respectively. CONCLUSIONS: Ir-192 showed
      good possibilities as a substitute for Ra-226 in brachytherapy for early oral
      tongue cancer.

PMID- 9252723
TI  - Serum levels of circulating intercellular adhesion molecule-1 in patients with
      breast cancer.
AB  - BACKGROUND: The outcome of breast cancer is usually determined by multiple
      factors. Circulating intercellular adhesion molecule-1 has been found to be
      increased in the circulation of patients with malignancy. This study was designed
      with the aim of evaluating the prognostic significance of circulating
      intercellular adhesion molecule-1 in breast cancer. METHODS AND MATERIAL: From
      December 1994 to May 1995, 50 patients with invasive breast carcinoma were
      included. Venous blood samples were collected before surgery and the serum levels
      of circulating intercellular adhesion molecule-1 were measured with an enzyme
      immunoassay method. The data of maximum tumor size, age, estrogen receptor
      status, lymph node status and TNM staging were collected and evaluated
      simultaneously with the serum levels of circulating intercellular adhesion
      molecule-1. Fifteen healthy subjects were used as control group. RESULTS: The
      mean value of circulating intercellular adhesion molecule-1 in patient group was
      463 +/- 92 ng/ml and that of the control group was 346 +/- 68 ng/ml and the
      difference was significant (p < 0.01). In univariable analysis, patients with
      maximum tumor size of 5 cm or greater (p < 0.01), more advanced lymph node status
      (p < 0.01) and more advanced TNM staging (p < 0.01) were shown to have
      significantly higher serum levels of circulating intercellular adhesion molecule
      1. However, in multivariable analysis, TNM staging was demonstrated to be the
      only independent factor (p < 0.01) related to significant, higher serum level of
      circulating intercellular adhesion molecule-1. CONCLUSION: Preoperative serum
      levels of circulating intercellular adhesion molecule-1 may reflect the severity
      of staging for invasive breast cancer and may be a promising, additive predictor
      which deserves further investigation.

PMID- 9252724
TI  - Immunohistochemical analysis of 4-aminobiphenyl-DNA adducts in oral mucosal cells
      of smokers and nonsmokers.
AB  - BACKGROUND: The "biologically effective dose markers", DNA and protein adducts,
      are a direct index of carcinogen induced cell damage and an indirect one of
      genetic susceptibility. This study aimed to examine the dose-response
      relationship for 4-Aminobiphenyl-DNA adducts in oral cells of smokers and non
      smokers. MATERIALS AND METHODS: An immunoperoxidase method with the monoclonal
      3C8 antibody, which recognizes 4-Aminobiphenyl-DNA, has been used for detecting
      DNA damage in oral cells of 12 smokers and 12 non smokers. RESULTS: Higher
      staining for 4-Aminobiphenyl-DNA was detected in the cells of smokers (187 +/-
      42) vs. non smokers (135 +/- 35) (p = 0.004), with a twofold range in relative
      staining for both groups, suggesting individual differences relevance in
      metabolizing carcinogens and/or repairing DNA damage. CONCLUSIONS: This non
      invasive method requiring small cell amounts is a tool for monitoring large
      groups of subjects at risk in primary prevention programs.

PMID- 9252725
TI  - Ultrasound in the detection of breast cancer associated with isolated clustered
      microcalcifications, mammographically identified.
AB  - The purpose of this work was to evaluate the effectiveness of US scanning in
      detecting breast cancer associated with isolated clustered microcalcifications
      (MC) mammographically identified. 52 isolated clusters of MC mammographically
      detected underwent histological examination. In all cases, ultrasonographic of
      (US) and cytologic examinations were performed for the improved definition of the
      nature of the MC. Fine needle aspiration was performed under radiographical (Rx)
      guidance, only in cases of US-negativity. Ultrasound detected a breast lesion in
      31 cases, out of which 24 (77.4%) were found to be carcinomas (invasive in 87.5%
      of the cases). Out of the remaining 21 US-negative cases, 7 (33.3%) were
      malignant lesions (15% invasive). Statistical analysis demonstrated that US
      positivity significantly correlated with the presence of malignant lesions (p <
      0.001). US-examination should also be performed in cases of isolated clustered
      microcalcifications for a more accurate selection of cases requiring histological
      verification.

PMID- 9252727
TI  - Racial variation in lung cancer.
AB  - Lung cancer claimed about 153,000 lives in 1994 in the United States. Despite
      research overall lung cancer survival has still not improved during the last 20
      years, with 5-year relative survival remaining about 13%. In addition several
      epidemiologic and molecular studies showed a difference in the incidence of lung
      cancer in the three major races. The aim of our study was to investigate the
      variations of race in lung cancer patients, in order to identify potential risk
      factors linked to the different racial status. In this light we compared a 10
      years lung cancer data of black population from Howard University Hospital,
      Washington D.C., U.S.A. and a 20 years data of white population from the Vienna
      University Hospital, Austria. Our results did not show any significant difference
      in mean age or tumor localization in both groups, but highlighted a remarkable
      difference in the incidence of the lung cancer histological types also according
      to the sex. In this respect it could be more successful to consider
      carcinogenesis like a protracted process of gene function deregulation in
      response to cell injury from exposure to genotoxic substances with individual
      specificity.

PMID- 9252726
TI  - Combination of chemotherapy and radiotherapy improves the cure rate in primary
      extranodal lymphomas of the head and neck (PLHN).
AB  - BACKGROUND: Since PLHN are rare, prognostic factors and the therapeutic strategy
      have not yet been clearly assessed. PATIENTS AND METHODS: Seventy-one patients
      with PLHN (44 stage I, 27 stage II; 54 with high-grade histology) received the
      following treatments: 5 radical surgery, 21 radiotherapy, 43 combined treatment
      (mainly chemotherapy plus radiotherapy) [CT] and 1 was not treated. RESULTS:
      Disease-related survival (DRS) and disease-free survival (DFS) were 84% and 69%
      at 5 years and 70% and 56% at 10 years. CT provided significantly better DRS and
      DFS than radiotherapy alone (92% and 81% vs 70% and 43% respectively), though the
      group receiving the CT included most of the patients with high-grade histology
      (37) and stage II (20). Outcome was not influenced by stage and site of
      involvement (Waldeyer's ring vs non-Waldeyer's ring). Multivariate analysis
      showed that favourable prognostic factors were age for DRS, high-grade histology
      and CT for DFS. CONCLUSIONS: Patients receiving the CT fared significantly
      better, though most of them had high-grade histology and stage II.

PMID- 9252728
TI  - Ethnic variations in lung cancer.
AB  - Cancer of the lung is the most frequent cancer in the world, but with wide
      geographical variation in risk. It is most spread among males of all races
      worldwide, the only exception being its incidence among Chinese women aged 70
      years and older. When comparing the different ethnic groups we have to consider
      that besides inhaling cigarette smoke actively or as a passive smoker the
      exposure to occupational carcinogens varies considerably according to different
      work places. In our study we compared 10 years of data from African-Americans in
      Howard University Hospital, Washington D.C. with 20 years of data from the white
      population in the University Hospital of Vienna, Austria. Ethnic patterns are
      generally consistent within each group in terms of both incidence and mortality.
      The difference in susceptibility between the sexes, the three major racial groups
      and already proven differences in genetic variations indicate the difference
      between individuals concerning the initiation and progression of lung cancer.

PMID- 9252729
TI  - Exanthem associated with Epstein-Barr virus illness.

PMID- 9252730
TI  - A dermatologic diary. Portrait of a practice.

PMID- 9252731
TI  - An update on molluscum contagiosum.
AB  - Molluscum contagiosum is a common viral infection of the skin, and occasionally
      the mucous membranes, manifesting as benign tumors. The characteristic appearance
      is of pearly, umbilicated papules. The disease is self-limited in immunocompetent
      hosts, but may be protracted in those who are immunocompromised. Multiple local
      therapeutic options are available; the use of systemic agents has been reported
      in recalcitrant cases or in patients in whom topical therapy is difficult to
      apply.

PMID- 9252732
TI  - Oral pigmentation representing Laugier-Hunziker syndrome.
AB  - Oral pigmentation is seen fairly commonly in dermatologic practice. Several
      conditions must be considered in the differential diagnosis. We present a patient
      whose condition highlights the clinical syndrome known as Laugier-Hunziker and
      provides the opportunity to review the clinical course, pathologic features, and
      literature of this uncommon syndrome.

PMID- 9252733
TI  - The "K" test for dosage of topical medication.
AB  - Firmly pressing a sheet of Kleenex to the skin after applying a cream of ointment
      aids the patient in dosing properly. A positive "K" test results when the Kleenex
      is soiled, indicating that a wasteful amount of salve has been used.

PMID- 9252734
TI  - Xanthoerythrodermia perstans and alopecia mucinosa in a patient with CD-30
      cutaneous T-cell lymphoma.
AB  - Xanthoerythrodermia perstans (XEP) is a distinctive variant of large-plaque
      parapsoriasis. Along with alopecia mucinosa and lymphomatoid papulosis, there is
      a strong association between large-plaque parapsoriasis and evolving cutaneous T
      cell lymphoma (CTCL). In some reports, large-plaque parapsoriasis was suggested
      to be a precursor lesion that converted to CTCL in 10 to 30 percent of cases. We
      describe a patient who presented clinically with both XEP and alopecia mucinosa
      and was subsequently shown to have CD-30 CTCL.

PMID- 9252735
TI  - Allergic contact dermatitis to propylene glycol in calcipotriene ointment.
AB  - A woman developed a pruritic exacerbation of her methotrexate-dependent psoriasis
      after applying topical calcipotriene ointment. Patch test reactions were positive
      to propylene glycol 1 percent and white petrolatum, but to none of the other
      ingredients of the medication. Physicians would be advised to patch test patients
      to both the therapeutic medication and the excipients of topical substances to
      which patients have adverse reactions. By so doing, an allergic reaction to one
      or more of the excipients may be found, thus the patient may be provided the
      benefit of the topical medication by using it in a form that does not contain the
      allergenic substance.

PMID- 9252736
TI  - Acute generalized exanthematous pustulosis secondary to diltiazem therapy.
AB  - Acute generalized exanthematous pustulosis in a rare pustular exanthem that is
      most commonly drug induced. We report a case occurring secondary to diltiazem
      therapy and briefly review the typical characteristics of this entity.

PMID- 9252737
TI  - Dermatophytosis in healing herpes zoster lesions.
AB  - Fungal infection of the face is frequently misdiagnosed, since the typical
      ringworm, erythematous, slightly scaling, indistinct borders are only uncommonly
      seen on the face. Herpes zoster is a common infection caused by the varicella
      zoster virus that transmits varicella (chickenpox). Granulomatous reactions such
      as granuloma annulare, pseudolymphoma, sarcoidal reaction, and eruptive
      keratoacanthoma have been described in herpes zoster scars. We describe here the
      first reported case of dermatophytosis occurring in healing herpes zoster
      lesions. This condition has not been previously reported.

PMID- 9252739
TI  - Transthoracic fine needle aspiration cytology of lung for suspected malignancy:
      an audit of cytological findings with histopathological correlation.
AB  - Transthoracic fine needle aspiration cytology (TFNAC) is an invasive procedure
      and should therefore be subject to regular review. We report an audit of TFNAC
      from 146 patients. One hundred and thirty-six samples (93%) were adequate and 86
      were malignant, 16 suspicious and 34 contained no malignant cells. TFNAC was the
      sole means of diagnosis of malignancy in 55 patients. However, further
      pathological data were available in 58 of the adequate samples; TFNAC was
      malignant in 31, suspicious in eight and contained no malignant cells in 19. All
      malignant TFNAC were confirmed (absolute sensitivity = 85%; positive predictive
      value = 100%); as were five of eight with suspicious cytology. Of 19 patients
      with negative TFNAC, nine were subsequently found to have a malignancy
      (specificity = 68%).

PMID- 9252738
TI  - Clobetasol propionate emollient 0.05 percent: hypothalamic-pituitary-adrenal-axis
      safety and four-week clinical efficacy results in plaque-type psoriasis.
AB  - Two clinical trials were conducted to evaluate the safety and antipsoriatic
      efficacy of a new 0.05 percent emollient formulation of clobetasol propionate
      (CP). In a crossover study of hypothalamic-pituitary-adrenal (HPA)-axis effects
      in 12 patients with psoriasis or eczema, 1.5 gm of CP emollient, applied to
      lesions twice daily for seven consecutive days, resulted in fewer patients with
      serum cortisol concentrations < 10 micrograms/100 mL than CP cream 0.05 percent
      (1vs 4); such concentrations were seen in two other patients during both
      treatment phases. A double-blind, randomized, parallel-group clinical trial in
      patients with moderate to severe plaque-type psoriasis showed that four weeks'
      treatment with CP emollient 0.43 to 0.5 gm twice daily (n = 35) was significantly
      more effective than emollient vehicle (n = 39) in reducing total signs/symptoms
      and scaling by Day 4, erythema and skin thickening by Day 8, and pruritus by Day
      15. CP emollient was rated superior to vehicle by Day 4 in physician's gross
      assessment ratings and by Day 15 in patient's self-assessment ratings. In all
      assessments, CP emollient continued to be superior to vehicle during the
      remainder of the treatment period and two-week posttreatment period. No
      significant differences were observed in tolerability or serum cortisol effects
      during the course of the study.

PMID- 9252740
TI  - Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology
      using the cytospin method; improvement through multidisciplinary clinical audit.
AB  - A breast FNA cytology service for palpable breast lumps was commenced in 1989
      using the cytospin method. Over the following 6 years 2314 aspirates were
      received. The results were audited in detail in 1990, 1991/1992 and 1994.
      Multidisciplinary clinical audit meetings followed each audit cycle. Practice
      change was agreed after each audit. Each audit cycle was followed by demonstrable
      improvement in the complete sensitivity of the technique, being respectively 79%,
      88% and 96%. The cytospin method is a viable alternative to the conventional
      smear method.

PMID- 9252741
TI  - Routine audit of breast fine needle aspiration (FNA) cytology specimens and
      aspirator inadequate rates.
AB  - In an attempt to improve the quality of the breast FNA specimens we instigated a
      continuing audit of this procedure in this hospital. All FNAs since 1990 have had
      the following recorded: mode of aspiration, e.g. freehand or image guided,
      patient presentation (screening or symptomatic), patient diagnostic category,
      cytological diagnosis and final histological diagnosis. Aspirator performance was
      assessed by means of the inadequate aspiration rate (IR) of FNAs performed on
      patients with a final diagnosis of cancer (FDC) and diagnostic category A
      patients (clinically or radiologically malignant lesions). An ongoing annual
      review of the performance of all the aspirators was undertaken, all of whom
      received individual feedback. Counselling and further training were offered where
      indicated by poor performance. Over the period 1990-1995 a total of 13537 FNAs
      were performed by 27 aspirators. The IR on category A and FDC cases over this
      period was 16.0% and 18.1%. The best performance achieved by an aspirator in a
      calendar year was an IR of 3.6% with no inadequate specimens in either FDC or
      category A lesions, and the best performance over the entire period was an
      average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The
      overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases
      from 12.2% to 21.7%. There was a significant improvement in individual junior
      aspirator performance when their first year was compared with their last year on
      the unit. In some cases a deterioration in intra-aspirator performance was
      observed, from an IR of 6% to 33%. The overall IR rate of the unit remained
      stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared
      to be largely due to a high proportion of the aspirations being performed by
      experienced personnel with consistent IRs. However, concealed within the overall
      rate there were some poor performers who benefited from counselling and/or
      further training. These results indicate an important role for audit in
      identifying poor aspirators who benefit from targeted training and advice,
      thereby improving the quality of FNA specimens, and ultimately patient care.

PMID- 9252742
TI  - Immunocytochemical staining of effusions; an external quality control study in
      The Netherlands.
AB  - In The Netherlands an external quality control study of immunocytochemical (IC)
      staining of effusions was initiated, consisting of three test rounds. The 12
      participating laboratories received samples of malignant effusions (runs 1, 2 and
      3), and five unstained control specimens prepared from the same material in runs
      2 and 3. The laboratories used their own protocols to prepare and stain the
      samples ('in-house' specimens). Two persons viewed and scored the slides
      following preset criteria concerning number and morphology of diagnostic cells,
      background staining and staining specificity. Better scoring results were found
      for control specimens, compared with 'in-house' specimens, primarily caused by
      cell loss in the latter. This finding underlines the view that high quality IC
      needs well organized processing and staining procedures, and warrants external
      quality control systems.

PMID- 9252743
TI  - The value of lymph node imprint cytodiagnosis: an assessment of interobserver
      agreement and diagnostic accuracy.
AB  - The aim of this study was to assess the reliability of cytodiagnosis of lymph
      node imprints without fixed tissue sections. One hundred randomly selected
      archival cases were used in the study. These air-dried May-Grunwald-Giemsa
      imprint slides were assessed independently and blind by three pathologists. Cases
      were assigned to one of four diagnostic categories: reactive changes, non
      Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and secondary malignancy. Each
      broad diagnosis was compared with the 'correct' reviewed histological diagnosis
      to calculate interobserver agreement and diagnostic accuracy. The overall kappa
      score (+0.59) was indicative of moderate agreement. The mean pathologist
      diagnostic accuracy was 78%, with complete agreement with the histological
      diagnosis in 61% of cases. The main diagnostic difficulties were in the
      distinction between reactive changes and NHL and distinguishing NHL from HD.
      Further diagnostic classification, e.g. typing of lymphomas and subclassification
      of Hodgkin's disease, was not found to be reliable using the imprints alone. With
      these limitations in mind, pathologists should be able to use lymph node imprints
      for cytodiagnosis in selected cases. The study also emphasized the utility of
      imprints as a corollary to the histology and as a tool for cytology training and
      continuing education.

PMID- 9252744
TI  - Image analysis of low magnification images of fine needle aspirates of the breast
      produces useful discrimination between benign and malignant cases.
AB  - Fine needle aspirates of the breast (FNAB) (n = 362; 204 malignant, 158 benign),
      prepared by cytocentrifuge methods and stained by the Papanicolaou technique,
      were analysed using a semi-automated image analysis system at a low magnification
      which precluded resolution of nuclear detail. The measured parameters were
      integrated optical density, fractal textural dimension, number of cellular
      objects (single cells and contiguous groups of cells), distance between cellular
      objects (mean, s.d., skewness and kurtosis), area of cellular objects (mean,
      s.d., skewness, kurtosis) and the nearest neighbour statistic. The cases were
      divided into a 200-case training set and a 162-case test set. Analysis was
      performed by logistic regression and the multi-layer Perceptron type of
      artificial neural network. Logistic regression and the neural network produced
      similar performances with a sensitivity of 82-83%, specificity 85% and a positive
      predictive value for a malignant result of 85%. A non-parametric analysis of all
      the predictor variables showed that all except the mean area of cellular objects
      and the s.d. of this measurement were significant discriminants (P < 0.05), but
      most were highly interrelated and this was reflected in the selection of only
      three predictor variables by forward and backward conditional logistic
      regression. This study shows that much diagnostic information is present in low
      power views of FNAB, and that image analysis could form the basis of a semi
      automated decision-support aid.

PMID- 9252745
TI  - The influence of the cervix on smear quality. I: Atrophy. An audit of cervical
      smears taken post-colposcopic management of intraepithelial neoplasia.
AB  - Out of 951 smears taken from women attending a hospital cytology clinic, 122 were
      found to be of poor quality. Twenty-eight percent of these were associated with
      clinical and/or cytological atrophy, and in 91% of these the main adverse factor
      affecting smear quality was scantiness. The relative risk of obtaining a scanty
      smear was found to be 4.8 times greater in women in whom clinical atrophy was
      identified when compared with those with no atrophy. It is suggested that a
      reduction in the number of scanty, and hence potentially inadequate, smears in
      the screening programme may be achieved by the use of more appropriate sampling
      implements in all women in whom there is clinical evidence of atrophy. Further
      review of alternative sampling methods is indicated.

PMID- 9252746
TI  - Cervex brush versus vaginal-cervical-endocervical (VCE) triple smear techniques
      in cervical sampling.
AB  - Cervex brush sampling was compared with the conventional triple vaginal-cervical
      endocervical (VCE) smear technique. Nine hundred and fifty-nine Cervex brush
      smears and 1064 VCE smears were studied. All smears with both methods were
      technically satisfactory for evaluation. Endocervical cells were found in 90.7%
      and metaplastic cells in 73.3% of Cervex brush samples and in 92.5% and 64.1% of
      VCE samples, respectively. There were significantly more metaplastic cells in
      smears from premenopausal women. Low grade squamous intraepithelial lesion (SIL)
      was found in three Cervex brush samples and in two VCE samples. High-grade SIL
      was found only in one Cervex brush sample. Benign cellular changes were found in
      142 Cervex brush samples and in 144 VCE samples. Sampling with the Cervex brush
      is efficient, simple and fast and gives high quality cervical smears for
      cytological evaluation.

PMID- 9252747
TI  - Arias-Stella changes in cervicovaginal specimens.

PMID- 9252748
TI  - Quality assurance in cervical cytopathology.

PMID- 9252749
TI  - The growth fraction of normal human epidermis.
AB  - In human epidermis, germinative cell production is determined by three
      parameters: the cell cycle time, the loss of cycling cells by programmed cell
      death and the proportion of keratinocytes actively engaged in the cell cycle or
      growth fraction. The last parameter is still a subject of debate as the
      identification of a proliferative cell with certainty is impossible. Two indirect
      methods (grain count dilution of labelled cells and continuous labelling) suggest
      that non-proliferative cells may exist in the germinative compartment of human
      epidermis. Results obtained in vitro demonstrate that keratinocytes can be
      blocked in certain conditions in a state of quiescence similar to a G0 phase.
      Increasing evidence suggests that, as in mouse epidermis, the germinative
      compartment of human epidermis is and is divided into a small proportion of stem
      cells (10%) with a high proliferative potential, a larger proportion of transit
      amplifying cells with a limited proliferative potential (50%) and postmitotic
      cells committed to undergo terminal differentiation (40%). In this hierarchical
      arrangement, most of the nonproliferative cells belong to the postmitotic
      compartment. If this model is correct, the germinative cell population in a
      quiescent or G0 state is a small proportion of the stem cell compartment and has
      therefore little influence on the kinetics of normal human epidermis.

PMID- 9252750
TI  - Characterization of the nuclear deoxyribonucleic acid content and nuclear
      morphometry in 71 primary cutaneous melanomas.
AB  - BACKGROUND: While the determination of nuclear deoxyribonucleic acid (DNA)
      content (DNA ploidy level) and nuclear morphometry characterization has proved to
      be of prognostic value in melanocytic lesions, there are several ways of
      performing these determinations. OBJECTIVE: To identify which of 9 DNA ploidy-
      and 2 nuclear morphometry-related variables are of prognostic and/or diagnostic
      value in 71 primary melanomas. METHODS: Histological typing, Breslow depth
      determination, the evaluation of Clark's level of invasion and the 11
      quantitative variables (calculated in Feulgen-stained nuclei using computer
      assisted microscope analysis) determined for each melanoma were submitted to
      discriminant analysis. RESULTS: The discriminant analysis of image cytometric
      variables enabled specific cell subpopulations to be identified in histological
      and the Breslow-related groups, but not in the Clark-related ones. CONCLUSION:
      The characterization of melanoma heterogeneity by means of the identification of
      specific DNA ploidy level-related cell subpopulations in specific Breslow-related
      groups enables the problem of intra- and interobserver variability in Breslow
      depth determination to be reduced and therefore can help dermatologists in their
      daily routine.

PMID- 9252751
TI  - Sebum excretion in hidradenitis suppurativa.
AB  - BACKGROUND: Clinical and histological similarities between hidradenitis
      suppurativa and acne have been pointed out. The possible role of sebaceous glands
      in hidradenitis has not previously been investigated. Acne treatment, in
      particular is however not effective in hidradenitis. No previous information was
      found on regional sebum excretion in hidradenitis. OBJECTIVE: Investigate the
      sebum excretion (SE) and markers of cutaneous virilization in hidradenitis
      patients. METHODS: Sebutapes and scores of acne, hirsutes and alopecia in 16
      women with hidradenitis suppurativa were compared with 16 healthy controls.
      RESULTS: The SE and the number of active glands followed a similar pattern in
      both groups (face > axillae/genitofemoral fold, p < 0.0001) but no significant
      differences were seen between the two groups. No differences were seen in the
      median Body Mass Index, number of obese persons in either group or any of the
      clinical markers of virilization studied. CONCLUSION: No significant axillary,
      genitofemoral or facial seborrhea was found in hidradenitis. It is suggested that
      SE is not an important factor in the development of hidradenitis, and this may
      help explain the generally unsatisfactory therapeutic effect of retinoids in this
      disease. The results further suggest that general cutaneous virilization is not a
      feature of hidradenitis.

PMID- 9252752
TI  - Disaccharide analysis of skin glycosaminoglycan in localized scleroderma.
AB  - BACKGROUND: Altered metabolism of skin glycosaminoglycan has rarely been
      investigated in localized scleroderma in contrast to systemic sclerosis.
      OBJECTIVE: The aim of this investigation is to elucidate the change in skin
      glycosaminoglycan of localized scleroderma. METHODS: We analyzed 5 skin samples
      of localized scleroderma and 10 site-matched control skin samples using high
      performance liquid chromatography after 1-phenyl-3-methyl-5-pyrasolone labeling.
      RESULTS: The involved skin constantly showed an increased amount of delta Di
      4S(DS), the main disaccharide unit of dermatan sulfate, a decreased amount of
      delta Di-HA, the main disaccharide unit of hyaluronic acid, and an elevated ratio
      of delta Di-4S(DS)/delta Di-HA as compared with the uninvolved skin or the site
      matched control skin. CONCLUSION: These results correlate well with those
      findings in systemic sclerosis, indicating that the alteration in skin GAG may be
      closely related to the fibrotic process.

PMID- 9252753
TI  - Primary neuroendocrine carcinoma of the skin expresses tyrosinase mRNA: detection
      by a specific nested PCR technique.
AB  - BACKGROUND: Tyrosinase transcripts have been identified in a wide range of normal
      organs and neoplasms such as cutaneous nevi, breast carcinomas, liposarcomas and
      schwannomas. The cells responsible for these positive results have not been
      accurately identified yet, but they might correspond to either fully
      differentiated melanocytes, melanocytic precursors or cells bearing potential for
      melanocytic differentiation. OBJECTIVE: To assess the expression of tyrosinase
      mRNA in surgical resection specimens and peripheral blood samples from 2 patients
      with primary neuroendocrine carcinomas of the skin (PNCS). METHODS: The
      expression of tyrosinase mRNA transcripts was tested by means of a reverse
      transcriptase and nested PCR technique, using specific primers, in tissue samples
      from surgical specimens and heparinized blood samples from 2 patients with PNCS.
      RESULTS: The results of the test were positive in the 2 specimens of PCNS but
      negative in blood samples. CONCLUSION: Our findings provide further support for
      the hypothesis that PNCS originates from a pluripotent stem cell capable of
      neuroendocrine cell differentiation, keratin production, and, as reported herein,
      tyrosinase mRNA expression. It remains to be seen whether this technique can also
      be applied to patients with PNCS, as an adjunct to staging and treatment
      planning.

PMID- 9252754
TI  - Quality-switched ruby laser treatment of solar lentigines and Becker's nevus: a
      histopathological and immunohistochemical study.
AB  - OBJECTIVE: A histopathological and immunohistochemical study was initiated to
      assess changes in benign human pigmented skin lesions after quality switched ruby
      laser (QSRL) irradiation. METHOD: A total of 196 solar lentigines on 8 patients'
      forearms were irradiated in vivo, 13 biopsies were taken. Hematoxylin-eosin
      staining and immunohistochemical techniques using anti-S-100 and Fontana-Masson
      stainings, as well as cryosections stained with nitroblue tetrazolium chloride
      (NBTC), were employed for the evaluation of the specimens. RESULTS: Immediately
      after QSRL impact selective photothermal damage (vacuolization) of all pigmented
      epidermal and basal melanocytes, keratinocytes, superficial dermal melanocytes
      and melanophages could be observed in solar lentigines. Cryosections stained with
      NBTC featured minimal thermal damage of the surrounding tissue. One Becker's
      nevus was also exposed to the QSRL, biopsies were taken before and immediately
      after QSRL exposure. In this lesion, superficially located pigments were
      selectively damaged, but a fair amount of pigmented cells in adnexal structures
      persisted throughout this single course of QSRL treatment. Recurrence of
      lentigines was not observed. In Becker's nevus, following initial fading of the
      lesion, clinically reactive hyperpigmentation occurred 4 weeks later. CONCLUSION:
      We found that pigmented lesions featuring a moderate amount of pigment
      exclusively in and around the basal cell layer, like solar (actinic) lentigo, can
      be successfully removed by a single QSRL exposure selectively damaging epidermal
      and basal pigmented structures. Further investigations concerning QSRL treatment
      of dermally pigmented skin lesions have to be initiated.

PMID- 9252755
TI  - Ex vivo quality-switched ruby laser irradiation of cutaneous melanocytic lesions:
      persistence of S-100-, HMB-45- and Masson-positive cells.
AB  - AIM: To assess changes in human pigmented melanocytic skin lesions after quality
      switched ruby laser (QSRL) irradiation. METHODS: Investigations were performed ex
      vivo on 21 melanocytic pigmented lesions (10 nevus cell nevi, 2 pigmented dermal
      nevi, 4 congenital nevi, 3 lentigo maligna lesions, 2 superficial spreading
      melanomas) immediately after surgical excision. A total of 42 biopsy specimens
      was obtained for comparative investigations before and after QSRL impact.
      Electron microscopy was performed in 3 lesions. RESULTS: Hematoxylin-eosin
      stainings showed selective vacuolization of pigmented structures (melanin
      granules, melanophages, pigmented melanocytes, pigmented keratinocytes)
      immediately after QSRL irradiation due to selective photothermolysis.
      Cryosections stained with nitroblue tetrazolium chloride featured minimal thermal
      damage of the surrounding tissue proving the high selectivity of QSRL light.
      Immunohistochemical techniques employing anti-S-100, HMB-45 antimelanoma antibody
      and Fontana-Masson staining revealed selective photothermal damage
      (vacuolization) of basal melanin granules, pigmented basal melanocytes and
      epidermal keratinocytes, as well as pigmented superficial dermal melanocytes.
      Deeper melanocytes and nests of nonpigmented melanocytes persisted unaltered and
      retained their S-100 and HMB-45 positivity. Masson's staining revealed persisting
      dermal melanophages. Electron microscopy showed specific damage of both
      keratinocytes and melanocytes with numerous melanosomes and confirmed the light
      microscopic findings. Deeper dermal melanocytes containing only few melanin
      granules remained unaltered. CONCLUSION: In pigmented lesions extending into the
      dermis, deeper pigmented melanocytic cells (nevus cells) persist throughout a
      single course of QSRL exposure. Nonpigmented melanocytic cells remain totally
      unaffected by QSRL irradiation. Therefore QSRL therapy of melanocytic nevi and
      congenital nevi should only be performed in controlled studies. Long-term results
      have to be evaluated before recommendations can be given.

PMID- 9252756
TI  - Roaccutane treatment guidelines: results of an international survey.
AB  - BACKGROUND: Oral isotretinoin (Roaccutane) revolutionized the treatment of acne
      when it was introduced in 1982. METHODS: Twelve dermatologists from several
      countries with a special interest in acne treatment met to formally review the
      survey of their last 100 acne patients treated with oral isotretinoin. The
      primary purpose of the survey was to identify the types of acne patients who were
      prescribed oral isotretinoin and how the patients were managed. RESULTS: Of the
      1,000 patients reviewed, 55% of those who received oral isotretinoin had those
      indications treated historically, i.e. severe nodular cystic acne or severe
      inflammatory acne, not responding to conventional treatment. Forty-five percent
      of patients who were prescribed oral isotretinoin however had either moderate or
      mild acne. Most patients in this group had moderate acne (85%). However, 7.3% had
      mild acne on physical examination. The criteria for prescribing oral isotretinoin
      in this less severe group of patients included acne that improves < 50% after 6
      months of conventional oral antibiotic and topical combination therapy, acne that
      scars, acne that induces psychological distress and acne that significantly
      relapses during or quickly after conventional therapy. Treatment is usually
      initiated at daily doses of 0.5 mg/kg (but may be higher) and is increased to 1.0
      mg/kg. Most of the physicians aimed to achieve a cumulative dose of > 100-120
      mg/kg. Mucocutaneous side-effects occur frequently but are manageable while
      severe systemic side-effects are rarely problematic (2%). The teratogenicity of
      oral isotretinoin demands responsible consideration by both female patients and
      their physicians. Significant cost savings when treating acne patients with oral
      isotretinoin as compared to other treatment modalities were further proven in
      this study. CONCLUSIONS: Our recommendation is that oral isotretinoin should be
      prescribed not only to patients with severe disease but also to patients with
      less severe acne, especially if there is scarring and significant psychological
      stress associated with their disease. Acne patients should, where appropriate, be
      prescribed isotretinoin sooner rather than later.

PMID- 9252757
TI  - Cutaneous malakoplakia on the forehead.
AB  - A case of cutaneous malakoplakia in an 81-year-old woman in reported. A reddish
      slowly growing plaque had appeared on her forehead 13 years previously.
      Histopathology revealed a dense dermal granulomatous infiltrate consisting of
      lymphocytes and numerous histiocytes containing Michaelis-Gutmann bodies.
      Ciprofloxacin treatment resulted in partial involution of the lesion.

PMID- 9252758
TI  - Orifices at the lower neck: heterotopic salivary glands.
AB  - Heterotopic islands of salivary-gland tissue are rare and have been described in
      a number of sites in the head and neck. We describe a patient with salivary-gland
      fistulas in the lower third of the neck, without evidence of any other congenital
      abnormalities. The appearance of sinuses in association with heterotopic salivary
      gland tissue suggests that its embryologic origin may be from the branchial
      clefts. Surgical treatment is recommended.

PMID- 9252759
TI  - An unusual presentation of multiple congenital melanocytic nevi with a limb
      distribution.
AB  - We report a newborn in whom multiple small congenital melanocytic nevi (MN) were
      noted on the right side involving the scapular area, shoulder, upper arm and
      forearm. Such a limb distribution of small congenital MN has never been reported
      in the literature.

PMID- 9252760
TI  - Generalized drug reaction due to papaya juice in throat lozenges.
AB  - We report the case of a 55-year-old woman without a history of atopic disease or
      drug allergy who developed a maculopapular symmetric exanthematous rash about 2
      days after taking throat lozenges containing papaya juice. Patch tests gave
      negative reactions to the European standard series but were positive for papaya
      juice. A solution of 1% papain in water showed a weak and probably irritant
      reaction, while a 0.1% solution was negative. To our knowledge this is the first
      case report of systemic contact dermatitis to papaya without papain
      hypersensitivity.

PMID- 9252761
TI  - Generalized lichen nitidus with oral and nail involvement in a child.
AB  - The generalized form of lichen nitidus (LN) with oral and nail changes is
      extremely rare in childhood. We report a 10-year-old boy with generalized LN
      associated with oral involvement and onychodystrophy. Oral lesions showed
      yellowish papules on the gums. The nails had longitudinal striations and pits on
      the finger-nails, and transversal ridging of the big toes was found. Cutaneous
      and mucosal lesions as well as onychodystrophy spontaneously cleared within 8
      months.

PMID- 9252762
TI  - Cutaneous amebiasis in an Iranian immunodeficient alcoholic: immunochemical and
      histological study.

PMID- 9252763
TI  - Serum antibodies to parvovirus B19 in patients with pityriasis rosea.

PMID- 9252764
TI  - The petrified ear--a manifestation of dystrophic calcification.

PMID- 9252765
TI  - Acquired acromelanosis due to phenytoin.

PMID- 9252766
TI  - Gloves-and-socks syndrome in a patient with Epstein-Barr virus infection.

PMID- 9252767
TI  - Proliferating tricholemmal cyst should always be considered as a low-grade
      carcinoma.

PMID- 9252768
TI  - Lichen planus associated with metformin therapy.

PMID- 9252769
TI  - Collision of primary malignant neoplasms on the skin: the connection between
      malignant melanoma and basal cell carcinoma.
AB  - Several studies have reported the association of cutaneous malignant melanomas
      (MM) with carcinomas. Collision malignancies cases from our files were retrieved.
      Among a series of 78,000 primary cutaneous cancers, 11 were collision tumors of
      MM with basal cell carcinoma and 106 were basosquamous carcinomas while no
      association was found between MM and squamous cell carcinomas. It is concluded
      that coexisting and confluent malignancies of the skin might not always be a
      random event.

PMID- 9252770
TI  - Treatment of dystrophic epidermolysis bullosa with autologous meshed split
      thickness skin grafts and allogeneic cultured keratinocytes.
AB  - A 5-year-old boy with dystrophic epidermolysis bullosa (DEB), type generalized
      mitis, presented with a 2-year-old non-healing skin defect on the presternal and
      abdominal region. After debridement up to the middle dermis, the defect was
      grafted with autologous meshed split-thickness grafts from non-involved skin from
      the thigh and covered with allogeneic keratinocytes. The described method is a
      valuable therapeutic option in DEB patients who have donor skin areas with a
      preserved structure of the basement membrane zone.

PMID- 9252771
TI  - Healing rate and bacterial necrotizing vasculitis in venous leg ulcers.
AB  - Morbidity associated with venous leg ulcers is important in the elderly. The
      biological processes involved during attempts at healing are much more complex
      than in most models of experimental wounds. In addition, there is still
      controversy on deleterious effects elicited by both microorganisms and
      antiseptics on cells involved in the healing process. Using histology,
      immunohistochemistry and iterative computerized planimetry, we evaluated the
      bacterial load, the inflammatory aspects and the healing rate of leg ulcers
      present in 15 eligible women aged from 57 to 73 years. Each patient had at least
      2 chronic ulcers treated with hydrocolloid dressing alone or in combination with
      daily applications of povidone-iodine solution (PVP-I). The weekly reduction in
      wound area was superior for hydrocolloid+PVP-I treatment than in hydrocolloid
      treated ulcers. After a 4-week treatment, hydrocolloid-treated ulcers contained
      clumps of microorganisms and showed massive infiltration by phagocytes including
      Mac 387+ and factor XIIIa+ cells. Leukocytoclastic vasculitis was present as
      well. These features were less pronounced in ulcers treated with hydrocolloid+PVP
      I. In sum, a broad-spectrum antimicrobial such as PVP-I may be beneficial in
      reducing deleterious bacteria-related inflammation. As a result, the healing rate
      leg ulcers is enhanced.

PMID- 9252772
TI  - Experimental reproduction of polymorphous light eruption and benign summer light
      eruption by whole-body UVA irradiation.
AB  - The entity 'benign summer light eruption' (BSLE) has been introduced to make a
      clinical subdivision in the heterogeneous group of polymorphous light eruptions
      (PLE). Provocation tests for PLE are not always easy to perform and require
      expensive apparatus. Our purpose was to evaluate a provocation test that could be
      readily done by a dermatologist with a UVA cabin. Provocation tests are currently
      required in order to obtain a financial contribution from the social security
      services in Belgium. In addition, we were interested in determining whether the
      results of the provocation test would permit us to differentiate between the
      clinical entities of BSLE and PLE. We studied the efficacy of whole-body UVA
      irradiation for BSLE and PLE patients. A total of 45 patients was tested, of whom
      26 were diagnosed as having BSLE and 19 PLE. In the BSLE group, 24 patients (92%)
      presented lesions. In the PLE group, 15 patients (79%) had a reaction, but 3 had
      a positive UVB test. The mean dose to induce lesions was 65.96 J/cm2 for the BSLE
      group and 52.86 J/cm2 for the PLE group. We conclude that the whole-body UVA test
      is a high-performance provocation test for both BSLE and PLE patients although it
      cannot differentiate the two entities from one another.

PMID- 9252773
TI  - Pemphigoid presenting as atypical excoriated prurigo: regarding 11 cases.
AB  - The acquisition of bullous pemphigoid may have different aspects. The disease can
      be initiated via the development of an excoriated prurigo in which clinical and
      histological features do not initially suggest the diagnosis of pemphigoid. The
      presence of eosinophils, oedema or a cleft at the dermis-epidermis junction are
      not constant features of the histopathological picture. Distinguishing a bullous
      pemphigoid from a prurigo can only be achieved by direct immunofluorescence.

PMID- 9252774
TI  - Pulse steroid therapy for children's severe alopecia areata?
AB  - Seven children with severe, rapidly evolving alopecia areata (AA) were treated
      with pulse steroid therapy (PST). AA had been present for 3-44 weeks and involved
      more than 30% of the scalp. One patient had alopecia totalis. Intravenous
      methylprednisolone (5 mg/kg twice a day) was administered for 3 days. No serious
      side effects were noted. At the 12-month follow-up, complete regrowth had
      occurred in 5 patients (71%). The patient with alopecia totalis had no regrowth.
      PST appears to be a promising and safe treatment for extensive, recent-onset AA
      in children. No response is to be expected in alopecia totalis or long-standing
      AA.

PMID- 9252775
TI  - Dermo-epidermal stimulation elicited by a beta-lipohydroxyacid: a comparison with
      salicylic acid and all-trans-retinoic acid.
AB  - Although ageing has been thought to be irreversible, studies made during the last
      decade have shown that a few topical compounds may limit or improve the age
      related skin damages. The efficacy of tretinoin (all-trans-retinoic acid) in
      treating photoageing is well established. Identifying other compounds with
      similar effect and improved tolerance would be greatly valued. In this double
      blind study, a new beta-lipohydroxyacid compound was evaluated. To address a
      comparison between products, 6 volunteers completed a 4-week study using twice
      daily 0.025% tretinoin, 5% salicylic acid, 1.5% beta-lipohydroxyacid or vehicle.
      Immunohistochemistry and computerized image analysis were performed on skin
      sections from biopsies taken after treatment. We searched for changes in
      epidermal renewal (Ki-67 labeling), modifications in cytokeratin (56-65 kD) and
      filaggrin patterns, and in tumor necrosis factor alpha (TNF-alpha), Ulex
      europaeus and factor XIIIa expressively. The vehicle- and salicylic-acid-treated
      areas had an aspect similar to untreated control sites. Both beta-lipohydroxyacid
      and tretinoin induced enhanced epidermal proliferation and thickness with
      activation of factor XIIIa+dendrocytes. The effects were more pronounced at the
      tretinoin-treated site. We speculate that TNF-alpha might mediate some of the
      dermal effects. The beta-lipohydroxyacid mimics some of the stimulatory effects
      of tretinoin on the epidermis and dermis. This new compound should be listed
      among topical products boosting the skin tissues affected by ageing.

PMID- 9252776
TI  - Tufted angioma, a particular form of angioma.
AB  - Tufted angioma is a rare acquired cutaneous angiomatous proliferation
      characterized by slowly spreading erythematous macules and plaques, sometimes
      surmounted by nodular formations. Synonyms are progressive capillary hemangioma
      and Nakagawa's angioblastoma. Tufted angioma appears to be benign since follow-up
      studies did not report malignant transformation. This lesion must be
      distinguished from other vascular tumors, especially from Kaposi's sarcoma. If
      this lesion appears in an older patient, angiosarcoma should be excluded.

PMID- 9252777
TI  - Capillary-venous malformation in the labia majora in a 12-year-old girl.
AB  - The case of a capillary-venous malformation in the labia majora of a 12-year-old
      girl is reported. The tumour increased in volume with puberty. The authors
      present a differential diagnosis between immature haemangioma and vascular
      malformation. The diagnosis is based on clinical examination, ultrasound, nuclear
      magnetic resonance, arteriography and gynaecological exploration. This
      malformation can be excised locally.

PMID- 9252778
TI  - Acute generalized exanthematic pustulosis: a case with a lymphoma-like
      presentation.
AB  - A 28-year-old woman developed an acute generalized exanthematic pustulosis in
      association with a massive lymphadenopathy. A viral etiology seemed highly
      probable although a drug reaction could not be excluded.

PMID- 9252779
TI  - Severe erosive stomatitis: association with immunological diseases?
AB  - We present 2 cases of severe erosive stomatitis. The first case involves the rare
      association of an extensive, erosive lichen planus with a Castleman's tumor. The
      second case involves the association of lichen planus pemphigoides with severe,
      obstructive lung disease (bronchiolitis obliterans). We believe that in both
      cases the conjunction of these conditions is not fortuitous but perhaps due to an
      underlying immune dysfunction. With patients presenting a severe, therapy
      resistant, erosive stomatitis, one should be alerted to the possibility of
      immunological diseases and/or tumors.

PMID- 9252780
TI  - Overlap of sarcoidosis and rosacea.
AB  - Numerous descriptions have been applied to rosacea-like eruptions of the face,
      some of them remaining of questionable nosologic significance. A case of rosacea
      like syndrome with lacrimal, ocular and salivary involvement is described. The
      differential diagnosis and therapeutic response of this unusual association are
      discussed.

PMID- 9252781
TI  - Docetaxel-induced subungual hemorrhage.
AB  - Docetaxel (RP 56976 or Taxotere), a semisynthetic drug belonging to the family of
      taxoids, is a new chemotherapeutic agent used in phase II trials for breast,
      ovarian and lung cancer. We report 2 cases of subungual hemorrhages, which, to
      our knowledge, have yet to be cited in association with the use of docetaxel.
      Although not incapacitating, the patient should be made aware of the potential
      risk of this drug reaction.

PMID- 9252782
TI  - Baboon syndrome.
AB  - An 18-month-old patient developed Baboon syndrome after oral treatment with
      erythromycin syrup for a sore throat. The lymphoblastic transformation test was
      positive for erythromycin. Prick tests were negative although the intradermal
      test was positive at a concentration of erythromycin of 1:10,000. The biopsy
      showed a perivascular lymphocytic dermatitis. Local treatment with a potent
      corticoid improved the lesions after 3 days. The Baboon syndrome is uncommon
      among children. It has a pattern similar to systemic contact dermatitis with
      particular features (erythema in flexural areas). In our case, the role of
      erythromycin was documented. However, this antibiotic remains a relatively rare
      allergen.

PMID- 9252783
TI  - Regulation of protein kinase C: a tale of lipids and proteins.
AB  - Protein kinase C (PKC) is a family of serine/threonine kinases implicated in
      intracellular signalling events triggered in response to a large variety of
      agonists. Currently, 11 mammalian PKC isoforms have been identified which are
      divided into three groups, the calcium-dependent, the non-calcium-dependent and
      the atypical isoforms. Common to all members is the presence of an aminoterminal
      regulatory domain, which renders the kinase inactive by interacting with the
      carboxyterminal catalytic domain. Thus, intracellular PKC activation requires the
      release of this autoinhibitory restraint, which, as this review summarizes, may
      involve both interactions with lipids and proteins. Furthermore, post
      translational PKC phosphorylation events, required to convert PKC to an
      activation competent state, are discussed.

PMID- 9252784
TI  - Bryostatin 1 induces ubiquitin COOH-terminal hydrolase in acute lymphoblastic
      leukemia cells.
AB  - It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation
      of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B
      cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH
      terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells
      were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in
      morphology, surface immunophenotype, acid phosphatase and terminal
      deoxynucleotidyl transferase. Protein patterns of the parent and differentiated
      cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were
      studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic
      features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pl 34-5.3) was
      detected by 2 D PAGE in the differentiated, but not in parent cells. The presence
      of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2
      D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in
      parent and Bryo1-treated cells and was compared with 12-O-tetradecanoylphorbol-13
      acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of
      ubiquitin expression as detected by flow cytometry. Sodium borohydride, an
      inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh
      cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating
      effect is not fully understood. This study shows that UCH-L1 expression may play
      a major role in Bryo1-induced differentiation in pre-B-ALL.

PMID- 9252785
TI  - Micromethod for the fluorimetric determination of plasma N-acetyl-alpha-D
      galactosaminidase and study of some of its characteristics.
AB  - We have studied some characteristics of N-acetyl-alpha-D-galactosaminidase in
      human plasma using a sensitive and very simple fluorimetric (single tube
      incubation/fixation) micromethod. The enzyme has a pH optimum at 4.5, is linear
      on incubation during at least 6 h, is protected from inactivation at room
      temperature by acidification, and is stable on freezing (about 85% residual
      activity after 1 year at -20 degrees C). Enzyme kinetics indicate that the
      affinity for the substrate is low (K(m) value 7 mmol/l). By studying about 10
      possible effectors, no activation was found by detergents. As expected, the
      colorigenic p-nitrophenyl derivative substrate, N-acetylgalactosamine and
      galactose are low-affinity inhibitors. A histogram of 108 control samples showed
      a unimodal distribution pattern with a slight bias to the right. No
      pseudodeficients were found on analysis of 220 control plasma samples. Patients
      with alpha-galactosaminidosis had residual activity between 0.7 and 2.1%. In
      patients with 17 different lysosomal storage diseases, no increase was found
      except in mucolipidosis II and III. The main advantages of the method are its
      simplicity sensitivity, short incubation time requirement and economy in
      substrate consumption. The method can be used either for screening or diagnostic
      purposes of genetic N-acetyl-alpha-D-galactosaminidase deficiency.

PMID- 9252787
TI  - Kinetic studies of the effects of K+, Na+ and Li+ on the catalytic activity of
      human erythrocyte pyridoxal kinase.
AB  - Kinetic studies were conducted to examine the effects of K+, Na+ and Li+ on human
      erythrocyte pyridoxal kinase (PK) activity. A dialyzed hemolysate served as the
      PK source. The substrates used were pyridoxal (PL) and ATP. Determination of the
      enzymatic activity was based on HPLC separation and fluorimetric detection of PL
      and pyridoxal 5'-phosphate as semicarbazone derivatives. In comparison to the
      poor activity of PK assayed without monovalent cation, all tested cations are
      activators. Among them, K+ is the most effective, improving both PK affinity for
      the substrates and maximal velocity. Na+ increases maximal velocity and PK
      affinity for ATP but decreases it for PL. Li+ is a poor activator which seems to
      modify the enzymatic mechanism from a random to an ordered sequential pattern
      with ATP bound before PL. Results suggest that K+ and Na+ bind to PK on the same
      site while Li+ binds on another site. This hypothesis and the mechanism of
      monovalent cation-PK interaction are compared to other well-known K(+)-activated
      enzymes.

PMID- 9252786
TI  - The integrity of thiol groups is essential for catalytic efficiency of rat liver
      cholesterol ester hydrolase either in microsomal membranes or after
      solubilization.
AB  - Neutral cholesterol ester hydrolase from rat liver microsomes was inactivated in
      a dose and time-dependent manner by classical sulphydryl-reacting reagents such
      as p-hydroxymercuribenzoic acid, 5,5'-dithio-bis-(2-nitrobenzoic acid), N
      ethylmaleimide, or iodoacetate. The concentrations at which half-maximal
      inhibition of the native microsomal cholesterol ester hydrolase occurred (IC50)
      were 15, 68, and 370 mumol/l and 68 mmol/l, respectively. Only partial
      reactivation of the enzyme was observed under excess dithiothreitol or
      mercaptoethanol treatment. The stimulation of cholesterol ester hydrolase by the
      metal ions Ca2+ and Mg2+ was dependent on the integrity of the thiol groups.
      Solubilization of cholesterol ester hydrolase from membranes preserved its
      sensitivity towards sulphydryl reagents and thiols, as well as its ability to be
      activated by Ca2+ and Mg2+. Dithiothreitol, mercaptoethanol, and Ca2+ and Mg2+
      provided total protection of the enzyme against inactivation by thiol-reacting
      reagents. The results indicate that one or more thiol groups are either at the
      active centre of the native and solubilized forms of rat liver microsomal
      cholesterol ester hydrolase or are sufficiently near, to interfere with the
      catalysis when they are reacted.

PMID- 9252788
TI  - Steady-state kinetics of Thr35 and Thr39 mutants in human adenylate kinase by
      site-directed mutagenesis.
AB  - Adenylate kinase (AK; EC 2.7.4.3, hAK1) catalyzes the reaction: MgATP(2-)+ AMP2-
      reversible MgADP-(+) ADP3-. To elucidate the catalytic and structural roles of
      threonine residues in human AK, Thr35 and Thr39 mutants were analyzed by steady
      state kinetics. The K(m) values of T35P and T35Y were not changed for MgATP2- and
      AMP2-, and the kcat values were decreased by 1/39 compared to those of wild-type
      AK. Thr35 was suggested to be essential for catalysis. The K(m) values of T39S,
      T39V and T39P were increased 5.6- to 59.0-fold for AMP2-; however, the kcat
      values were not reduced. Although the K(m) values of T39F and T39L were
      unchanged, the kcat values were reduced by more than 1/57. Thr39 appears to play
      an important role in the binding of AMP2- and to be essential for catalysis. As
      noted above, a hydroxyl group of the Thr residue in human AK appears to be
      important.

PMID- 9252789
TI  - A variant alkaline phosphatase detected in a patient with lung cancer.
AB  - A variant alkaline phosphatase (ALP), with heat-sensitivity characteristics
      similar to that of the bone type, was found in the serum of a patient suffering
      from lung cancer. In disc polyacrylamide gel electrophoretic studies most of this
      enzyme had migrated to the region corresponding to liver ALP, with the remainder
      affecting bone ALP. Like kidney ALP, this ALP was markedly inhibited by 0.5
      mmol/l L-cysteine. The K(m) of this ALP for p-nitrophenylphosphate was 0.39
      mmol/l, similar to that of kidney ALP. The sugar moiety of this enzyme bore
      greater resemblance to that of kidney ALP than liver or bone ALP. However,
      immunoprecipitation of this particular ALP was strong with a monoclonal antibody
      against liver ALP and moderate with an antibody against bone ALP.

PMID- 9252790
TI  - Combined 3-methylglutaconic and 3-hydroxy-3-methylglutaric aciduria with
      endocardial fibroelastosis and dilatative cardiomyopathy in male and female
      siblings with partial deficiency of complex II/III in fibroblasts.
AB  - We report on 2 children, brother and sister, who presented with cardiomyopathy
      and muscular hypotonia at the age of B months. They both excreted significant
      amounts of 3-hydroxy-3-methylglutaric acid (3-HMG) and 3-methylglutaconic acid (3
      MGC) but no 3-methylglutaric acid (3-MG). Enzyme analysis in fibroblasts revealed
      normal activities of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase and of 3
      methylglutaconyl hydratase and other enzymes of 3-HMG metabolism. Loading tests
      with leucine did not affect the excretion of 3-HMG and 3-MGC. The girl died as a
      result of her cardiomyopathy, while the boy recovered and was treated with
      cardiac supportive therapy. He showed a steady improvement during his clinical
      course with biochemical normalization of the urinary excretion of 3-HMG,
      concomitant with marked improvement in the hypertrophic cardiomyopathy. In
      cultured fibroblasts from both patients a reduced activity of complex II/III of
      the respiratory chain was measured which may be the cause of this new type of 3
      HMG uria. Analysis of mitochondrial DNA heart muscle, liver and fibroblast
      culture of the patient did not reveal any major mitochondrial DNA rearrangements
      (deletion, duplication) or any point mutation that had been described in
      association with mitochondrial cardiomyopathy.

PMID- 9252791
TI  - Frontotemporal dementia: its rediscovery.
AB  - Frontotemporal dementia (FTD) is the second most frequent degenerative cause of
      dementia. Although described for more than a century, it remains often
      misdiagnosed, mistaken for Alzheimer's disease or psychiatric disorders, which is
      prejudicial to care and research. It is a clinical syndrome corresponding to at
      least three histological entities: (1) Pick's disease, (2) non-specific
      frontotemporal degeneration, (6 times more frequent), and (3) frontal lobe
      abnormalities associated with motor neurone disease. It never corresponds to
      Alzheimer pathology. It must be suspected in patients with behavioural dyscontrol
      predating memory impairment, without spatial disorientation and normal EEG.

PMID- 9252792
TI  - Visual disturbances and transurethral resection of the prostate: the TURP
      syndrome.
AB  - A 73-year-old man with a history of a cerebral and a cardiac vascular disease and
      atrial flutter developed visual disturbances characterized by vision being dark
      in both eyes and by seeing as through a color photographic negative immediately
      after an uncomplicated transurethral resection of the prostate (TURP) for
      prostatic hyperplasia under spinal anesthesia. There was complete remission of
      the symptomatology after 2.5 h. A cerebrovascular workup was negative.
      Considering postoperative hyponatremia and hypoosmality, we discuss the possible
      role of glycine-induced visual disturbances as described in the TURP reaction
      syndrome, to our knowledge an entity almost unknown in the neurologic literature.
      Glycine-induced visual disturbances should therefore be considered in the
      differential diagnosis of bilateral transient visual loss.

PMID- 9252793
TI  - The Besancon Stroke Registry: an acute stroke registry of 2,500 consecutive
      patients.
AB  - The purpose of this study was to estimate the frequency of various risk factors,
      courses and outcome of stroke subtypes in a large hospital-based stroke registry.
      The Centre Hospitalier Universitaire of Besancon is the only public hospital with
      a neurological department in the county to admit any unselected patient with an
      acute stroke. A prospective hospital-based registry using systematic computer
      coding of data was conducted. All patients were evaluated by standard testing
      (neuroimaging, Doppler ultrasonography and cardiac investigations). From 1987 to
      1994, 2,500 stroke patients with a first-ever stroke were included in the
      Besancon Stroke Registry. There were 1,425 men (mean age 66.1 years) and 1,075
      women (mean age 70.6 years). Ischemic stroke was present in 84% of the patients
      (cerebral infarction in 84.5% and transient ischemic attacks in 15.5%), primary
      intracerebral hemorrhage (PIH) in 14.2% and cerebral venous thrombosis in 1.8%.
      On the 1st day of the stroke 79.9% of the patients were admitted, 47.1% within 6
      h. In addition, stroke severity was well correlated with the time of the
      patient's admission. Past medical history of hypertension was the major risk
      factor occurring in 55.8% of all patients, followed by smoking, atrial
      fibrillation, ischemic heart disease, hypercholesterolemia and diabetes mellitus.
      Clinical presentation was distributed according to classical patterns. The in
      hospital mortality rate was 13.6% and was higher in patients with infarcts
      (13.7%) or PIH (25.6%). Logistic regression analysis determined independent
      predictive factors for death: deterioration at 48 h [odds ratio (OR) 10.1, 95%
      confidence interval (CI) 7.0-14.5], initial loss of consciousness (OR 4.5, 95% CI
      3.1-6.4), age > 70 (OR 2.6, 95% CI 1.8-3.8), complete motor deficit (OR 1.9, 95%
      CI 1.3-2.8), major cognitive syndrome (OR 1.5, 95% CI 1.1-2.3), hyperglycemia at
      admission (OR 1.007, 95% CI 1.004-1.01), female gender (OR 0.7, 95% CI 0.5-0.9)
      and regressive stroke onset (OR 0.2, 95% CI 0.1-0.5). The Besancon Stroke
      Registry is a useful tool for the study of the risk factors, clinical features,
      and the course of strokes in an early phase.

PMID- 9252794
TI  - Complementarity of contrast transcranial Doppler and contrast transesophageal
      echocardiography for the detection of patent foramen ovale in stroke patients.
AB  - All studies concerning the detection of patent foramen ovale (PFO) have compared
      transthoracic or transesophageal echocardiography (c-TEE) to transcranial Doppler
      ultrasound after contrast injection (c-TCD), but combining both techniques in the
      search of PFO has received no consideration. Our study aims to substantiate this
      claim in 37 patients with cryptogenic stroke. It includes two protocols for the
      detection of PFO to assess the complementarity of c-TCD and c-TEE performed
      simultaneously or separately. Firstly, we used a standardized protocol,
      performing c-TCD alone. Secondly, we used a standardized and a simultaneous
      protocol which associated c-TCD with c-TEE. When c-TCD and/or c-TEE found right
      to-left shunts, they were classified as minimal, intermediate and massive. c-TCD
      revealed all PFO detected by c-TEE in 24 patients out of 37 (65%). Furthermore, c
      TCD was positive for a PFO in 5 other patients whereas c-TEE was negative. The
      degree of right-to-left interatrial shunting varied according to the protocol: c
      TCD performed alone found 15 massive, 4 intermediate and 5 minimal shunts whereas
      10, 9 and 5, respectively, were detected by c-TCD when it was combined with c
      TEE. In contrast, c-TEE revealed 8 massive, 8 intermediate and 8 minimal shunts.
      c-TCD can identify minimal shunts missed by c-TEE and could be more relevant to
      detect massive shunts, particularly when not performed simultaneously with c-TEE
      because no sedation is required for c-TCD alone as opposed to c-TEE: thus
      patients are more cooperative and produce a better Valsalva strain. c-TEE
      confirms pulmonary shunts suspected by c-TCD and determines the morphologic
      characteristics of the interatrial septum. While previous studies opposed c-TEE
      against c-TCD for the detection of a PFO, we think that both techniques are
      complementary and that it is interesting to associate them, particularly when
      they are deferred, to increase the ability of detecting PFO and to specify the
      degree of right-to-left shunting.

PMID- 9252795
TI  - Clinical and electrophysiological phenotype of a homozygously duplicated Charcot
      Marie-Tooth (type 1A) disease.
AB  - Type 1A of Charcot-Marie-Tooth disease (CMT1A) is associated with a
      microduplication of chromosome 17 (region 17p11.2) which contains PMP22, an
      important gene for peripheral nerve myelination. Patients carrying two
      duplications are expected to have a more severe phenotype, close to the Dejerine
      Sottas syndrome. In this article, we report a family of 5 CMT1A patients in whom
      the unrelated father and mother carry a 17p11.2 duplication. The 2 daughters
      carry only one duplication (one given by the father, the other given by the
      mother), but the son carries two 17p11.2 duplications. Interestingly, the
      clinical phenotype of the son is more severe (scoliosis) compared to those of his
      sisters, but his motor nerve conduction velocities are in the range of a
      heterozygote CMT1A patient. The mechanisms leading to a more severe phenotype for
      CMT1A are discussed and may not be strictly related to lower nerve conduction
      velocities.

PMID- 9252796
TI  - Studies to assess if pizotifen prophylaxis improves migraine beyond the benefit
      offered by acute sumatriptan therapy alone.
AB  - Two multi-centre studies-one double-blind, placebo-controlled (study 1) and one
      open (study 2)-were set up to assess if pizotifen prophylaxis improved migraine
      beyond the benefit offered by acute sumatriptan therapy alone. Eighty-eight
      patients completed the blinded study and 63 patients completed the open study.
      Both studies were of crossover design with patients undertaking a 4 week run-in
      period prior to a 12-week treatment period. Following a 4-week washout period
      patients commenced a second 12-week treatment period on the alternative treatment
      regimen. All breakthrough attacks were treated with 100 mg oral sumatriptan with
      an optional 2 doses available to treat any recurrence within 24 h of taking dose
      1. Pizotifen was built up to a final daily dose of 1.5 mg over a 2-week period
      and patients remained on this dose for a further 10 weeks. Patients in the
      blinded study were given matching placebo tablets for one of the two treatment
      periods. The efficacy of sumatriptan was not affected by pizotifen. The median of
      the monthly attack rate experienced by patients was slightly lower whilst
      patients were on pizotifen and sumatriptan than while on placebo prophylaxis and
      sumatriptan or sumatriptan alone; study 1, 3.5 vs 3.9 attacks per month (p =
      0.008); study 2, 2.9 vs. 3.2 attacks per month (p = 0.23). Also, while on
      pizotifen and sumatriptan more patients had a greater proportion of their time in
      the study migraine-free. From the results of these studies it does not appear
      that pizotifen reduces migraine severity; regardless of the treatment regimen the
      initial headache severity of most attacks was moderate. Weight gains experienced
      by patients while on pizotifen and sumatriptan were greater than the weight gains
      experienced while on placebo prophylaxis and sumatriptan or sumatriptan alone
      (period 1); study 1, 2.6 vs. 1.0 kg (p = 0.002); study 2, 1.6 vs. -0.8 kg (p <
      0.0001). The combination of pizotifen and sumatriptan did not result in any
      additional adverse events other than those usually seen with each medication
      alone. In these studies, where the average number of migraine attacks was around
      4 per month, the benefits conferred by pizotifen were at the expense of the
      adverse events associated with the drug, particularly weight gain. Therefore the
      clinical benefit of treatment with pizotifen for patients who have less than 4
      attacks per month should be carefully reviewed as acute treatment with
      sumatriptan may be the most appropriate treatment. Pizotifen may be better
      reserved for those patients who have 4 of more attacks per month.

PMID- 9252797
TI  - Silent cerebral microembolism in asymptomatic and symptomatic carotid artery
      stenoses of low and high degree.
AB  - 124 carotid arteries of 62 patients with unilateral or bilateral carotid stenosis
      proven by selective angiography were investigated by transcranial Doppler to
      detect high-intensity transient signals (HITS) in the middle cerebral arteries
      (MCAs). HITS identified as embolic signals were detected in 29 of 124 (23.3%)
      MCAs and in all cases were asymptomatic. HITS were more common in the MCAs on the
      same side as high-degree (> 70%) carotid stenoses (24 of 57 = 42.2%) compared
      with low-degree (< 70%) carotid stenoses (5 of 28 = 17.9%, p < 0.05). No HITS
      were detected in the MCAs on the same side as normal (24) and occluded (15)
      carotid arteries. About the clinical features related to the stenoses, HITS were
      detected with a nonsignificant prevalence in the MCAs on the same side as
      symptomatic stenoses (16 of 43 = 37.2%) compared with asymptomatic stenoses (13
      of 42 = 30.9%) and a relationship between HITS number and time elapsed from
      symptoms was observed. All symptomatic carotid stenoses > 70% (33) underwent
      endarterectomy and none of them showed HITS after surgical treatment. These
      results encourage the feasibility of prognostic studies to evaluate the clinical
      significance of embolic signals and suggest that silent microembolism could be
      helpful in selecting a high-risk group of asymptomatic or < 70% carotid stenoses
      for endarterectomy.

PMID- 9252799
TI  - Dysphagia in Parkinson's disease.
AB  - The prevalence of dysphagia and its relationship to the nutritional status of the
      subject was examined in 53 patients with Parkinson's disease (PD). Forty-three
      patients (81%) had swallowing difficulties but this was mild in most of them. The
      nutritional status of patients with PD was similar to that of age- and sex
      matched control subjects. Disease duration and severity correlated with the
      severity of dysphagia. The study also identified tremor and speech disturbances
      as the main predictors of dysphagia in PD.

PMID- 9252798
TI  - The perceived effects of smoked cannabis on patients with multiple sclerosis.
AB  - Fifty-three UK and 59 USA people with multiple sclerosis (MS) answered
      anonymously the first questionnaire on cannabis use and MS. From 97 to 30% of the
      subjects reported cannabis improved (in descending rank order): spasticity,
      chronic pain of extremities, acute paroxysmal phenomenon, tremor, emotional
      dysfunction, anorexia/weight loss, fatigue states, double vision, sexual
      dysfunction, bowel and bladder dysfunctions, vision dimness, dysfunctions of
      walking and balance, and memory loss. The MS subjects surveyed have specific
      therapeutic reasons for smoking cannabis. The survey findings will aid in the
      design of a clinical trial of cannabis or cannabinoid administration to MS
      patients or to other patients with similar signs or symptoms.

PMID- 9252801
TI  - The effect of COMT inhibition by tolcapone on tolerability and pharmacokinetics
      of different levodopa/benserazide formulations.
AB  - This double-blind, placebo-controlled, randomized, crossover study was designed
      to evaluate the effects of catechol-O-methyltransferase (COMT) inhibition by
      tolcapone on the pharmacokinetics of levodopa given as four different
      formulations of levodopa/benserazide: 50/12.5 mg, 100/25 mg, 200/50 mg (all
      standard release), or 100/25 mg (controlled release). Sixteen healthy volunteers,
      in two groups of 8, were given two different levodopa/benserazide formulations
      with and without tolcapone in random order on 4 days, each separated by a 7-day
      washout period. On each treatment day, 200 mg tolcapone or placebo (blinded) was
      taken orally 1 h before and 3 and 7 h after a single (unblinded) dose of
      levodopa/benserazide. All treatment combinations were well tolerated. Continuous
      inhibition of erythrocyte COMT activity by approximately 75% was observed over 13
      h with tolcapone; this was unaffected by levodopa/benserazide formulation.
      Tolcapone had similar effects on plasma levodopa concentrations with the standard
      release formulations: half-life and bioavailability increased approximately 2
      fold compared with placebo, and maximum plasma concentration (Cmax) and time to
      Cmax (tmax) were unaffected, except for a slight increase in Cmax with the
      levodopa/benserazide 200/ 50 mg formulation. With the controlled-release
      formulation, tolcapone increased the levodopa area under the plasma
      concentration/time curve approximately 2-fold. Although levodopa tmax appeared
      delayed, the absorption phase was unaffected. Onset of levodopa effect is
      therefore not likely to be delayed when tolcapone is coadministered with this
      formulation. Regardless of levodopa/benserazide formulation, 3-O-methyldopa
      formation was reduced by 90% with tolcapone compared with placebo. These results
      show that tolcapone could potentiate the antiparkinsonian effects of levodopa
      independently of levodopa/benserazide formulation.

PMID- 9252800
TI  - A laser microprobe mass analysis of brain aluminum and iron in dementia
      pugilistica: comparison with Alzheimer's disease.
AB  - We report a laser microprobe mass analysis of aluminum and iron content in the
      hippocampus and in the inferior temporal cortex in 2 cases of dementia
      pugilistica (DP), 4 cases of Alzheimer's disease (AD), and 3 controls. There was
      a predominant accumulation of Al and Fe within neurofibrillary tangles (NFT) in
      both DP and AD cases. High levels of Al and Fe were also detected in the nuclei
      of NFT-free and NFT-containing neurons, as well as in neuropil probe sites in
      these cases. In both regions, NFT contained substantially higher levels of Al and
      Fe in DP compared to AD cases. These findings suggest the existence of an
      association between the deposition of Al and Fe and NFT formation, and support
      the possibility of a global dysregulation of Al and Fe transport in DP and AD.

PMID- 9252802
TI  - Myasthenia gravis following IFN-alpha-2a treatment.

PMID- 9252803
TI  - Varicella with acute motor axonal neuropathy.

PMID- 9252804
TI  - Electrophysiological and MRI findings in 2 patients with Listeria
      rhombencephalitis.

PMID- 9252805
TI  - Arthrodesis of the first metatarsophalangeal joint to salvage failed silicone
      implant arthroplasty.
AB  - Between 1987 and 1992, all patients presenting to the senior author with a
      symptomatic failed silicone implant arthroplasty refractory to conservative
      treatment were converted to a metatarsophalangeal joint arthrodesis. Internal
      fixation was achieved with either dual intrameduilary threaded Steinmann pins or
      an obliquely placed AO compression screw and a three- or four-hole one-third
      tubular dorsal neutralization plate. Bone grafting was used to maintain hallux
      length. Successful arthrodesis was achieved in all five feet in patients with
      rheumatoid arthritis. Subjectively, patients improved from an average of 0.69
      before arthrodesis to 4.89 after arthrodesis. The average walking tolerance
      improved from 1.11 to 4.80, and the overall level of satisfaction improved from
      0.0 to 4.79. The patient's ability to wear shoes improved from 0.87 to 3.1.
      Successful arthrodesis produces a foot that is more functional and durable than
      excisional arthroplasty. Subjectively, these patients stated that their level of
      pain, walking tolerance, and overall satisfaction improved significantly after
      the arthrodesis. Clinically, there was no evidence of transfer lesions,
      tenderness, or hallux subluxation. Hallux length was well maintained after
      surgery with bone grafting, but it was more difficult to obtain the alignment
      goals. The average postoperative metatarsophalangeal dorsiflexion angle was 15.6
      degrees and the first metatarsophalangeal angle was 3.1 degrees. Despite this,
      patient satisfaction was high. Arthrodesis of the first metatarsophalangeal joint
      using a bone graft to salvage failed silicone implant arthroplasty produces
      acceptable subjective and radiographic results. Although technically demanding,
      it provides long-term stability to the hallux, restores weightbearing, and allows
      for maintenance of a propulsive gait. We recommend this procedure instead of an
      excisional arthroplasty to maintain high level of function and overall patient
      satisfaction.

PMID- 9252806
TI  - Plantar pressure distribution after resection of the metatarsal heads in
      rheumatoid arthritis.
AB  - Surgical correction of the forefoot in rheumatoid arthritis by resection of all
      metatarsal heads in combination with a resection arthroplasty of the first
      metatarsophalangeal joint showed excellent and good results in 20 (77%) of 26
      cases and satisfactory and fair results in 6 (23%) of 26 cases. Twenty-six feet
      in 16 patients were operated on by a plantar approach and examined after a mean
      follow-up period of 50 months (range, 24-90 months). Seventy-three percent of the
      patients were free of pain. In 75 (58%) of all 130 investigated toes, complete
      absence of load distribution was noted. In the remaining 55 (42%) toes, we
      observed a variable extent of function, depending on the length of resection.
      Although toe function is better in minimal metatarsal resection, single excessive
      length or plantar spike formation revealed pressure peaks in the metatarsal area.
      Metatarsal head resection provided reduction of pain and correction of severe
      deformities, and permitted the patients to wear ordinary shoes in 24 (93%) of 26
      cases.

PMID- 9252807
TI  - Endoscopic plantar fascia release: a cross-sectional anatomic study.
AB  - Endoscopic plantar fascia release is a new procedure proposed to treat heel pain
      and plantar fasciitis. The purpose of this study was to assess the structures at
      risk during plantar fascia release using this method. Ten fresh-frozen cadaver
      feet were divided into two groups. All specimens underwent cannula placement
      inferior to the plantar fascia. Five-of the specimens had plantar fascia release
      using the endoscopic technique. Six of the specimens were then frozen and cut in
      transverse, sagittal, and coronal sections to visualize the relationship between
      the cannula and plantar fascia and surrounding structures. Gross dissection was
      performed on the remaining four specimens. The amount of plantar fascia released,
      the relationship to the nerve to abductor digiti minimi, and the fascia of the
      abductor hallucis muscle were assessed. The average distance from the cannula
      margin to the nerve to the abductor digiti minimi was 6 mm at the medial border
      of the plantar fascia. The average amount of plantar fascia released was 90%.
      Although a complete release was attempted, the fascia to the abductor hallucis
      was not released in any of the specimens. The nerve to the abductor digiti minimi
      was not damaged in any of the specimens. On coronal sections, the nerve was
      closer to the cannula and plantar fascia release than previously reported.

PMID- 9252808
TI  - Varus tilt of the tibial plafond as a factor in chronic ligament instability of
      the ankle.
AB  - The authors performed a radiographic study of 136 patients with acute ligament
      sprains and 85 patients with chronic lateral ligament instability of the ankle.
      Varus angulation of the tibial plafond, varus angulation of the line passing both
      malleolar ends, and varus angulation of the medial malleolus were measured on the
      AP views, and dorsal angulation of the tibial plafond was measured on the lateral
      views. The varus angles of the tibial plafond, the line passing both malleolar
      ends, and the medial malleolus were larger as mean values in patients with
      chronic ligament instability than in the patients with acute ligament sprain. The
      varus tilt of the tibial plafond is more often seen in patients with chronic
      ligament instability of the ankle than in patients with acute ligament sprains.

PMID- 9252809
TI  - Traumatic dislocations of the lesser toes.
AB  - Traumatic dislocations of lesser metatarsophalangeal joints (DLMTPJ) and lesser
      interphalangeal joints (DLIPJ) are very uncommon. A retrospective analysis of 31
      cases and of the 16 reported cases was conducted to clarify our understanding of
      the pathomechanics, the role of associated injuries, recommended treatment, and
      outcome. Hyperextension with axial loading produces the injuries. Ipsilateral
      foot fractures or dislocations often occur and thus may compromise the outcome.
      Thirty percent of DLMTPJ and virtually all DLIPJ require open reduction; most
      often, the plantar plate prevents closed treatment of either DLMTPJ or DLIPJ. At
      follow-up, treated isolated DLMTPJ have few or no complaints; disability persists
      in patients who suffered concomitant displaced ipsilateral midfoot or forefoot
      fractures or dislocations. Neglected DLMTPJ remain symptomatic. All reduced DLIPJ
      are pain free.

PMID- 9252810
TI  - Successes and pitfalls in the healing of neuropathic forefoot ulcerations with
      the IPOS postoperative shoe.
AB  - Unnecessary amputations can be avoided with the healing of foot ulcerations in
      neuropathic feet. Traditional approaches have relied on relieving plantar and
      other extrinsic foot pressures. A retrospective review was performed of the
      office records of patients with Wagner grade 1 and 2 neuropathic forefoot
      ulcerations who were prescribed an IPOS (Niagara Falls, NY) postoperative shoe. A
      total of .33 patients were in the chart review. Twenty-three of these patients
      were located and agreed to participate in a telephone survey. Patients showed a
      compliance of 78%. Seventy-seven percent of the patients healed their ulcers and
      wore prescription inserts and extra-depth shoes at a mean of 8 weeks. Seventy
      eight percent of our telephone survey patients were either satisfied or satisfied
      with reservations. Problems or complications from wearing the IPOS postoperative
      shoe occurred with 38% of all patients.

PMID- 9252811
TI  - Arthroscopic treatment of anterior ankle impingement.
AB  - Ankle arthroscopy has recently allowed the elaboration of less invasive
      techniques for the treatment of anterior impingement. Its indications,
      advantages, and drawbacks in this application are discussed. Between 1987 and
      1994, 133 patients were treated for ankle impingement. Among them, 58 patients,
      37 men and 21 women (mean age, 28.5 years), who had failed a trial of
      conservative treatment were treated by means of tibiotalar arthroscopy. Twenty
      seven were athletes engaged in sports with abnormal stressing of the ankle.
      According to McDermott's radiological classification, there were 15 stage I
      cases, 23 stage II, 13 stage III, and 7 stage IV. Preoperative evaluation with a
      modified version of McGuire's scoring system gave 50 cases rated as "poor" (< 60
      points) and 8 cases rated as "fair" (60-67 points). Treatment consisted of
      removal of adhesions, cartilage shaving, and removal of the bone impingement with
      powered instruments, curettes, or small osteotomes. Follow-up was from 8 to 62
      months (mean, 21.5 months). The postoperative McGuire ratings were 37 good, 13
      fair, and 8 poor. There were no major complications. Recurrence of impingement
      was observed in four cases of stage III and IV. The conclusion is drawn that
      ankle arthroscopy is a sound method for the treatment of anterior impingement.
      Even in cases with severe joint cartilage impairment, it plays a therapeutic role
      as a means of postponing a possible arthrodesis.

PMID- 9252812
TI  - Nonsurgical treatment of monarticular nontraumatic synovitis of the second
      metatarsophalangeal joint.
AB  - Thirteen patients with second metatarsophalangeal joint synovitis in 14 feet were
      seen during 4.5 years for monarticular nontraumatic synovitis of the
      metatarsophalangeal joint. They were treated with a nonsurgical regimen of intra
      articular corticosteroids, along with the modification of a regular laced shoe to
      provide a rockerbottom effect. Nine feet of 8 patients were available for follow
      up at an average of 75 months. Seven feet were asymptomatic, with no recurrence.
      One patient with bilateral involvement continued with symptoms unchanged. There
      were no recurrences. The treatment was unsuccessful for one patient who underwent
      surgical synovectomy. The above regimen seems to satisfactorily resolve the
      symptoms in 70% of the patients treated.

PMID- 9252813
TI  - A comparison of two motion analysis systems for the measurement of two
      dimensional rearfoot motion during walking.
AB  - The purpose of this study was to compare two-dimensional rearfoot motion during
      walking measured by a traditional video-based motion analysis system to that of
      an electromagnetic analysis system. Twenty-five individuals (15 men, 10 women)
      with a mean age of 29.8 years served as subjects for this study. The results of
      the study showed that there was a high correlation (r = 0.945) between the mean
      motion paths produced by the two systems, indicating that they were very similar.
      The electromagnetic motion analysis system was able to produce these similar
      results in a fraction of the time required by the video-based system.

PMID- 9252814
TI  - Fastest reduction of posttraumatic edema: continuous cryotherapy or intermittent
      impulse compression?
AB  - Sixty patients with foot or ankle trauma were randomized and treated in three
      groups. In intermittent impulse compression, an air pad under the foot was
      inflated every 20 seconds, thus activating the venous foot pump. In continuous
      cryotherapy, ice water circulates between the ice box and the cold pad. The ice
      water was changed once per day. In standard therapy, the injured extremity was
      treated with cool packs, which were changed 4 times per day. Beginning at
      admission, every 24 hours the circumference was measured around the ankle,
      midfoot, and forefoot. After 24 hours of treatment, there was a 47% reduction in
      swelling with the A-V impulse System, 33% with continuous cryotherapy, and 17%
      with cool packs. After 4 days of postoperative treatment, the A-V impulse System
      reduced the swelling by 74% versus 70% with continuous cryotherapy and 45% with
      cool packs. Both new methods are preferable to cool packs. Because of the better
      preoperative results, the A-V impulse System proved to be the most effective
      device.

PMID- 9252815
TI  - Intraosseous gouty invasion of the talus.
AB  - A 34-year-old man presents with a cystic lesion of the talus that has developed
      over the last 3 years and a history of a single first metatarsophalangeal attack
      of gout. Radiodiagnostic studies confirmed the cyst and an associated
      osteochondritic lesion but showed no evidence of avascular necrosis. At
      arthroscopy, chalk-like material was removed from the cyst, which was
      histologically compatible with tophaceous gout. The lesion was debrided, and the
      patient was then treated with antihyperuricemic medication; radiographic evidence
      of cyst resorption was seen after 9 months of treatment.

PMID- 9252816
TI  - Analysis of clinical grading scales for the foot and ankle.
AB  - To evaluate grading methods used to report clinical results, we reviewed 1,607
      articles related to the foot and ankle published in six orthopaedic journals from
      1980 through July 1993. Many clinical studies use criteria such as patient
      satisfaction to grade results. A numeric score or grade was used in 346 articles:
      238 used a grade only, 90 used a numeric score and grade, and 18 used a numeric
      score only. The numeric score or grade was usually, but not always, reported with
      details of the individual clinical factors that composed the score or grade.
      Twenty-three articles used a score before and after treatment. Statistics were
      used in 62 articles, and in 6 of those the statistics were used to compare
      clinical condition before and after treatment. This study demonstrated the array
      of grading methods used in selected orthopaedic journals and indicated the need
      for standardized grading techniques to allow for more meaningful interpretation
      of the orthopaedic literature.

PMID- 9252817
TI  - Foot and ankle research priority: report from the Research Council of the
      American Orthopaedic Foot and Ankle Society.

PMID- 9252818
TI  - Nonunion of a fracture of the lateral malleolus: a case report and review of
      literature.

PMID- 9252820
TI  - Treatment of plantar fasciitis with night splint and shoe modifications
      consisting of a steel shank and anterior rocker bottom.

PMID- 9252819
TI  - Nonoperative management of posterior tibial tendon dysfunction.

PMID- 9252821
TI  - Does supported housing protect recent immigrants from psychological distress?
AB  - Psychological distress measured by the Talbieh Brief Distress inventory was
      compared between two groups of immigrants: consumers of supported housing (N =
      302) and non-consumers living in community settings (N = 419), matched by sex,
      age and education level. Overall, distress level was found to be significantly
      lower in consumers of supported housing than in non-consumers. Consumers also
      exhibited significant lower hostility, obsessive-compulsive and paranoid ideation
      symptoms, but they were similar to nonconsumers on level of depression, anxiety
      and sensitivity. The results suggest that supported housing protects recent
      immigrants from environmental stresses to a greater extent than community
      residence.

PMID- 9252822
TI  - Students' stress in China, Japan and Korea: a transcultural study.
AB  - In this transcultural comparison of stress among Chinese, Japanese and Korean
      students, the authors examined stressors with the Stress Questionnaire Form for
      College Students, strategies for coping with Ways of Coping-Revised, and physical
      reactions to the stressors with the Physical Symptom Scale of Stress. Compared to
      the Japanese and Korean students, Chinese students had a multitude of stressors
      and experienced the highest level of stress. In coping with stressful events,
      Koreans were the most active, Chinese the least active and Japanese were
      intermediately active. Physical symptoms were found to be most serious in Koreans
      and less serious in Chinese and Japanese. Coping techniques seemed unrelated to
      alleviating physical symptoms in Koreans but mildly related in Chinese and
      Japanese.

PMID- 9252823
TI  - Users' views of a drop-in project for the homeless.
AB  - Homeless adults attending a drop-in voluntary project were approached to assess
      their views on the project, pathways into homelessness, physical and mental
      health needs and history of substance misuse. Over a six week period, 70 users
      were interviewed. Of these 54 (77%) were men and the rest women. Twenty five
      (35%) were living in insecure accommodation. A significant proportion 61% (43)
      acknowledged having suffered from emotional or mental health problems in the past
      and nearly half (47%) admitted to having received a psychiatric diagnosis. Nearly
      one third reported past criminal record. The use of substances (drugs and
      alcohol) was fairly common. There were no ethnic differences in the findings
      although the numbers from ethnic minorities remain small. This is not a typical
      homeless sample but the findings suggest vulnerability of such a group. The group
      was by and large satisfied with the open access and flexible approach of the
      project. The findings are discussed in relation to the acceptable services
      provided by voluntary organisations and suggestions made for further studies.

PMID- 9252824
TI  - From Leros asylum to community-based facilities: levels of functioning and
      quality of life among hostel residents in Greece.
AB  - The pattern of mental health care in Greece is undergoing a major transformation.
      The Leros Projects I and II supported the development of 13 community hostels
      located throughout the Greek mainland. These hostels provide residential care to
      more than 100 former psychiatric inpatients, mainly from Leros asylum. The
      present study evaluates the impact of the resettlement process on the residents'
      perceived quality of life (QoL) together with an examination of the residents'
      psychiatric and behavioural functioning four years after the move from hospital.
      The target sample (n = 99) comprised of individuals who may be considered
      'chronic' psychiatric patients with a long history of institutionalisation and
      many are socially deprived with few family ties. The residents' functioning
      profile indicates a range of different levels of abilities. The QoL findings show
      that the majority of residents (70%) perceived the movement from the traditional
      hospital regime to the community hostels as being a positive change and expressed
      their satisfaction (74%) with the new living situation. This study demonstrates
      that even the most dependent, chronic psychiatric patients in Greece can be
      maintained in community settings and are able to articulate generally reliable
      and valid responses concerning the impact of service changes.

PMID- 9252825
TI  - Interpretive group psychotherapy and dependent day hospital patients: a
      preliminary investigation.
AB  - A small group of highly dependent day hospital patients, together with a small
      number of 'potential' day hospital referrals sharing similar characteristics,
      were treated in twice weekly interpretive group psychotherapy for between seven
      and nine months. At the end of treatment three of four day hospital patients had
      made a successful separation from the day hospital, and at nine month follow-up
      outcome appeared improved. Only two of the six non-day hospital patients remained
      in the group, the reasons for which are discussed. The method of evaluation
      proved manageable, although it would be more appropriate to studies involving
      larger numbers and possibly control interventions. It is suggested that the role
      of interpretive group psychotherapy in rehabilitation deserves further
      investigation.

PMID- 9252826
TI  - Does quality of life differ in schizophrenic women and men? An empirical study.
AB  - In our study of 617 schizophrenic patients, we tested the hypothesis that women
      have a better objective and subjective quality of life than men. Better social
      integration of women was confirmed. Objective conditions had a significant but
      quantitatively small impact on satisfaction with specific life domains. Better
      social integration did not, however, lead to more satisfaction among
      schizophrenic women. Satisfaction with life in general was better predicted by
      satisfaction in different life domains than by objective circumstances.
      Predictors of satisfaction with life were not equal for both sexes. Rather than
      confirming quantitative differences in subjective quality of life, our data
      support the existence of gender-specific processes and contexts of subjective
      valuation.

PMID- 9252827
TI  - Mu-Ghayeb: a culture-specific response to bereavement in Oman.
AB  - Studies with normal subjects and patients suggest that in grieving the dead, the
      bereaved has to go through a progressive course of psychological and social
      reorganization. The Mu Ghayeb belief in Omani society involves a complete denial
      of the loss for a relatively long period with the expectation of the return of
      the dead. This belief persists even after an elaborate ritual of burial and a
      prescribed period of mourning. The deceased are expected to leave the grave after
      burial and join their families when the spell placed on them by a sorcerer is
      broken or counteracted. Although the Mu Ghayeb belief is inconsistent with Muslim
      religion, it may be explained in terms of sudden and untimely death which used to
      be rife in the seafaring Omani society.

PMID- 9252828
TI  - Surgical reconstruction for deep venous insufficiency.
AB  - All patients with significant venous stasis disease should undergo noninvasive
      evaluation to determine the magnitude, precise location, and etiology of the
      problem (i.e. obstruction and/or reflux). Patients who fail aggressive medical
      therapy (compression and skin care) and who have significant symptoms should be
      considered candidates for surgical correction. The majority of patients screened
      will have a significant component of superficial venous insufficiency with or
      without the presence of incompetent perforating veins. In this case we address
      the superficial and perforating venous systems prior to consideration of deep
      venous reconstruction. When correction of superficial venous incompetence fails
      to improve the patient's symptoms, they are then considered for deep venous
      reconstruction. Patients with primary venous insufficiency are typically good
      candidates for direct valvuloplasty performed using the open or angioscopic
      techniques, while patients with damaged (post thrombotic) or absent valves are
      best managed by vein valve transplantation or segmental transposition. Results
      for both valvuloplasty and vein valve transplantation demonstrate good
      intermediate term valvular patency and ulcer healing. It appears that when used
      as part of a complete treatment protocol addressing superficial, deep, and
      perforating venous systems, as well as attention to skin care and appropriate
      compressive therapy that surgical reconstruction for deep venous reflux affords
      significant benefit to our patients.

PMID- 9252830
TI  - A multiple comparison procedure to control the strong stagewise family error rate
      in comparing test treatments and a control.
AB  - Multiple comparisons are commonly seen in clinical trials and many other fields.
      An example, which is the focus of this paper, is the comparison of several test
      treatments (possibly different doses of a compound) with placebo (control). It is
      well known that steps must be taken to control the type I error rate when
      multiple testing is performed. We introduce the concept of the strong stagewise
      family error rate and propose a multiple comparison procedure to control this
      error rate. The proposed procedure is compared to Dunnett's step-down procedure
      when there are two test treatment groups and a placebo group.

PMID- 9252829
TI  - A sequential trial of pain killers in arthritis: issues of multiple comparisons
      with control and of interval-censored survival data.
AB  - A large clinical comparison of pain killers used in the treatment of arthritis
      was conducted using a sequential design. The trial presented two major
      challenges: there were three treatments to be compared, and patients were
      assessed annually for up to 7 years. Treatment comparisons were made by selecting
      appropriate pairwise comparisons, to which standard theory could be applied.
      Rules concerning actions to take in the event of each stopping criterion being
      reached were evaluated by simulation. The annual assessments were used to create
      an interval-censored survival time: the year during which "disease progression"
      first occurred.

PMID- 9252831
TI  - Analysis of a within-subject design with covariates.
AB  - This paper deals with a method of analyzing incomplete data, forming a monotone
      pattern, from a within-subject design with baseline measurements. An assumption
      of multivariate normality with antedependence structure is made for both the
      baseline measurements and the response measurements. Adjusted means for the
      period-by-sequence cells and their dispersion matrix are obtained. Large sample
      tests are proposed for testing various hypotheses. A numerical example is given
      to illustrate the methodology.

PMID- 9252832
TI  - Drop-outs and a random regression model.
AB  - The implications of drop-outs for power of random regression model (RRM) tests of
      significance for differences in the rate of change produced by two treatments in
      a randomized parallel-groups design were investigated by Monte Carlo simulation
      methods. The two-stage RRM fitted a least squares linear regression equation to
      all of the available data for each individual, and then ANOVA or ANCOVA tests of
      significance were applied to the resulting slope coefficients. The tests of
      significance were adequately protected against type I error, but power was
      seriously eroded by the presence of drop-outs. Simple endpoint analyses with
      baseline and time-in-treatment covaried proved more robust against the power
      degradations.

PMID- 9252833
TI  - Application of rank analysis of covariance methods to analysis of multiple
      anatomical regions with treatment for seborrheic dermatitis.
AB  - This paper presents the advantages of rank analysis of covariance in contrast to
      the Mantel-Haenszel procedure in the presence of a covariate. In this paper, data
      from a clinical trial with an indication for seborrheic dermatitis, which
      afflicts multiple anatomical regions, is presented. This paper presents analysis
      performed using both the Mantel-Haenszel procedure and rank analysis of
      covariance for separate anatomical regions, as well as for the combined
      anatomical regions. The analysis for the combined anatomical regions involves
      weighted sums over different strata.

PMID- 9252834
TI  - Reference ranges for screening preclinical drug safety data.
AB  - Reference ranges are used in preclinical drug safety studies to screen
      experimental data for atypical values. The methods used most often to construct
      sample reference ranges are essentially large sample methods and may flag too few
      "atypical" values. It is better to generate finite sample reference ranges by
      modifying existing methods used for constructing tolerance intervals. We define
      validity and efficiency for reference ranges and discuss the validity and
      efficiency of the methods described. A finite sample distribution-free method
      emerges as the clear winner.

PMID- 9252835
TI  - Multipoint dissolution specification and acceptance sampling rule based on
      profile modeling and principal component analysis.
AB  - In dissolution testing, multiple dissolution measurements at specific time points
      are needed in quality control when the compliance of the product requires
      controlled dissolution throughout the time course. The dissolution specification
      based on general multivariate confidence region was proposed by Chen and Tsong
      (8). This paper presents two alternative procedures when the dissolution profile
      consists of important measurements at more than 4 time points. In the first
      procedure, when the dissolution profile can be described by a physical curve
      through modeling, the dissolution specification is developed based on the
      confidence region of the parameters of the physical curve. In the second
      procedure, the principal components (PCS) as the linear combinations of the
      dissolution measurements are identified and dissolution specification is set
      based by the confidence intervals of the values of principal components. In both
      approaches the specification can be set at lower dimensions than the general
      multivariate confidence region approach. A single-stage acceptance rule can be
      used in both approaches by first projecting the dissolution values of each tablet
      in the new testing batch onto the determined parameters axes (through modeling in
      modeling approach and through projection on the selected PCS in principal
      component approach). Then check if the projections of the new tablet fall within
      the specifications. Finally, count the number of tablets that fall outside the
      specification limits and reject the batch if the proportion of out-of
      specification tablet is high and accept the lot for release if the proportion is
      low.

PMID- 9252836
TI  - The difference of means of two indirect unpaired groups in receptor
      autoradiography.
AB  - We present an approximate method to compare the difference of the means of two
      groups of populations by indirect unpaired data. This indirect data structure
      occurs in receptor autoradiography, where the tissue distribution of receptors is
      visualized in the form of ligand bindings. This visualization is indirect because
      we can only observe and measure nonspecific bindings in one autoradiograph and
      total bindings in another autoradiograph. The distribution of receptors is
      obtained by subtracting the nonspecific bindings from the total bindings. Besides
      the reasoning of our method, an example is given using our experimental data.

PMID- 9252837
TI  - Evaluation of the uncertainty of molecular mass measurement by electrospray
      ionization mass spectrometry.
AB  - Electrospray ionization (ES) is a novel method used in mass spectrometry (MS) for
      producing gas-phase ions from substances in solutions. Common practices for
      molecular mass estimation from ES spectra summarize the spectrum as a single peak
      giving no estimate of uncertainty or treat each peak as an independent molecular
      mass measurement. ES-MS data analysis showed that each peak in an ES spectrum
      does not always provide an independent measure of molecular mass. Underestimation
      of measurement uncertainty is a possible result. An elementary time series
      method, the Yule-Walker equations, was applied to molecular mass estimation from
      ES data.

PMID- 9252838
TI  - Directional efficient tests or classic alpha adjustments?

PMID- 9252839
TI  - Colonic irrigation and the theory of autointoxication: a triumph of ignorance
      over science.
AB  - Autointoxication is an ancient theory based on the belief that intestinal waste
      products can poison the body and are a major contributor to many, if not all,
      diseases. In the 19th century, it was the ruling doctrine of medicine and led
      "colonic quackery" in various guises. By the turn of the century, it had received
      some apparent backing from science. When it became clear that the scientific
      rationale was wrong and colonic irrigation was not merely useless but potentially
      dangerous, it was exposed as quackery and subsequently went into a decline. Today
      we are witnessing a resurgence of colonic irrigation based on little less than
      the old bogus claims and the impressive power of vested interests. Even today's
      experts on colonic irrigation can only provide theories and anecdotes in its
      support. It seems, therefore, that ignorance is celebrating a triumph over
      science.

PMID- 9252840
TI  - Multiple esophageal webs: treatment and follow-up of seven patients.
AB  - We have treated seven patients with multiple esophageal webs without a
      predisposing disorder. The patients ranged in age from 34 to 61 years and had
      suffered from dysphagia for 4 to 26 years. None had skin disease, a history of
      ingestion of a potentially caustic substance, or evidence of gastroesophageal
      reflux disease by history or endoscopy. All patients responded to esophageal
      dilation, but dysphagia recurred in all during follow-up ranging from 6 months to
      4 years, often requiring repeated dilation. Study of our patients and similar
      patients reported previously leads us to believe this unusual disorder is
      congenital.

PMID- 9252841
TI  - Endoscopic discrimination of gastric ulcers.
AB  - Because endoscopists are concerned about misidentifying a gastric neoplasm as a
      benign gastric ulceration (GU), routine endoscopic biopsy and documentation of GU
      healing has been recommended. With the decreasing incidence of gastric cancer in
      the United States, the increased use of nonsteroidal anti-inflammatory drugs, and
      the concern over medical care costs, this practice standard has been questioned.
      To study the utility of endoscopic GU follow-up, we reviewed all cases of GU in
      the Duke GI-Trac database over a 7-year period. We found 1,189 patients diagnosed
      with GU who underwent 1,698 upper endoscopies. Of these, 130 patients underwent
      serial esophagogastroduodenoscopy until GU healing was documented. We identified
      19 cases of gastric neoplasm. Endoscopic impression correlated with histology as
      follows: positive predictive value, 36%; negative predictive value, 99.3%;
      specificity, 90%; and sensitivity, 84%. Two of the three cases of GU in which the
      endoscopist's impression was benign but histology revealed malignancy occurred in
      the setting of an acute gastrointestinal bleed. We conclude that more than 99% of
      the time an endoscopist's initial impression that a GU is benign is correct.
      Using the Medicare reimbursement scheme, approximately $150,000 would be spent to
      detect one early gastric cancer. Our results further question the utility of
      serial endoscopic evaluation of GUs until healing.

PMID- 9252842
TI  - Concurrent use of antiulcerative agents.
AB  - Many physicians prescribe more than one antiulcerative agent (AUA) simultaneously
      to the same patient, although there is little evidence to support this practice.
      The purposes of this study were to (a) determine patient factors associated with
      the concurrent use of these agents and (b) estimate the excess costs generated by
      the prescription of multiple rather than a single agent. We conducted a case
      control study of concurrent AUA users among New Jersey Medicaid enrollees age 65
      years and older. To evaluate the excess cost generated by the ongoing
      prescription of an additional AUA, we measured the additional drug expenditures
      associated with each regimen of concurrent use. Nearly 1 in 15 AUA users (6.6%)
      met our conservative definition of concurrent AUA use. In a multiple logistic
      regression model, previous gastrointestinal procedure, use of a nonsteroidal anti
      inflammatory drugs, nursing home residency, and recent hospitalization for more
      than 20 days were all predictors of concurrent use of more than one AUA. No
      association was found with age, sex, or number of pharmacies used. The upper
      bound estimate of the cost generated by the concurrent prescription of a second
      AUA was $210 (range: $2-$942) over the 180-day study period, with a lower bound
      of $151 (range: $1-$449). Annually, such excess cost would range from $301 to
      $420 per patient. This would account for between $457 million and $637 million
      per year for the nation's elderly if these patterns are generalizable. Despite
      the lack of evidence of therapeutic benefit from multiple concurrent AUA use in
      most patients, this practice is fairly common. Besides introducing the risk of
      additional costs and side effects in the absence of additional efficacy, the
      costs of such duplicative prescribing are substantial.

PMID- 9252843
TI  - Electrogastrography and gastric emptying scintigraphy are complementary for
      assessment of dyspepsia.
AB  - We have tried to correlate abnormalities in electrogastrography (EGG) and gastric
      emptying (GE) with symptom severity in patients with functional dyspepsia.
      Seventy-two patients with functional dyspepsia underwent EGG, GE, and symptom
      severity quantitation. EGGs were assessed for dominant frequency (DF), percentage
      of time of DF in the 2 to 4 cpm range, and postprandial-fasting DF power ratio.
      Solid-phase GE scintigraphy was assessed for 2-hour percentage retention.
      Symptoms of upper abdominal discomfort, early satiety, postprandial abdominal
      distension, nausea, vomiting, and anorexia were graded as none (0), mild (1),
      moderate (2), and severe (3); the sum represented a total symptom score. The EGG
      was abnormal in 11 of 22 (50%) patients with delayed GE compared with 11 of 50
      (22%) with normal GE (p < 0.025). The total symptom scores were higher in
      patients with both delayed GE and abnormal EGG compared with patients with normal
      GE and EGG, normal GE and abnormal EGG, and delayed GE and normal EGG. We
      conclude that EGG abnormalities are more common in dyspeptic patients with
      delayed GE. Patients with both delayed GE and abnormal EGG have more severe
      symptoms. Our results suggest that EGG and GE complement each other in
      correlating symptoms to gastric dysmotility.

PMID- 9252844
TI  - Predictors of patient cooperation during gastrointestinal endoscopy.
AB  - We examined a number of patient variables, including three different scales of
      preprocedure patient anxiety, to determine which best predicted patient
      cooperation and satisfaction with gastrointestinal endoscopy. We prospectively
      evaluated 251 patients undergoing outpatient diagnostic
      esophagogastroduodenoscopy and colonoscopy under conscious sedation. All were
      given a questionnaire on arrival to our endoscopy center that included three
      measures of preprocedure anxiety: (a) a single question asking how anxious the
      patient was (termed "Anxiety I" scale); (b) a visual linear analog scale of
      anxiety; and (c) the Hospital Anxiety and Depression scale. Patient cooperation
      during the procedure was rated by the attending endoscopist. Patients were
      telephoned the next day to complete a questionnaire assessing their endoscopic
      experience. Logistic regression analysis was used to construct models for
      predicting which patients were most likely to have difficulty during their
      procedures from both the endoscopists' and the patients' standpoint. Statistical
      analysis identified three parameters that by themselves significantly correlated
      with patient cooperation during endoscopy: age (p = 0.008), Anxiety I scale (p =
      0.03), and visual linear analog anxiety score (p = 0.02). When used together,
      age, type of procedure, and Anxiety I scale were the best predictors of patient
      cooperation from the standpoint of the endoscopist. Age, type of procedure,
      Anxiety I scale, and education level were the best predictors of satisfaction
      with endoscopy from the perspective of the patient. Good cooperation during
      endoscopy was associated with greater patient satisfaction.

PMID- 9252845
TI  - Crohn's disease in late adolescence: acute onset or long-standing disease?
AB  - We studied retrospectively a group of 53 patients with Crohn's disease, diagnosed
      between 18 and 21 years of age. They had all undergone a thorough medical
      evaluation at age 17 before military service. They thus served as a unique group
      in whom the natural course of the disease, duration of signs and symptoms before
      diagnosis, and delay in diagnosis could be assessed. Other than a more frequently
      elicited history of nonspecific mild recurrent abdominal pain in childhood in the
      patient group, medical history, physical growth, sexual development, and
      laboratory parameters of inflammation did not differ in the patient group and the
      healthy control group. Crohn's disease in this group of young adults is likely
      one of acute onset and did not begin as an exacerbation of a more subtle and
      prolonged process.

PMID- 9252846
TI  - Sincalide: a cholecystokinin agonist as an aid in endoscopic retrograde
      cholangiopancreatography--a prospective assessment.
AB  - Although several approaches to overcome difficult bile duct cannulation and gain
      free biliary access have been popularized, the use of gastrointestinal peptide
      hormonal agents such as sincalide, a cholecystokinin agonist, as an alternative
      method has not been evaluated. I have carried out a prospective, nonrandomized
      assessment of the use of sincalide for diagnostic and therapeutic endoscopic
      retrograde cholangiopancreatography (ERCP). Overall, sincalide was used in 23%
      (32/136) of ERCPs in 26.6% (29/109) patients. Sincalide was successfully used to
      (a) obtain a cholangiogram after initial failure using only a standard catheter
      in 12 of 19 patients; (b) precisely locate the papilla and bile duct orifice in
      five of five patients; (c) locate the bile duct opening to obtain a cholangiogram
      and free cannulation during needle-knife papillotomy or weeks later in five of
      seven and three of three patients, respectively; and (d) gain free access (deep
      cannulation) to the bile duct after a cholangiogram in 5 of 10 patients. The
      selected use of sincalide appears to enhance the success of diagnostic and
      therapeutic ERCP; however, perseverance alone may account for some of this
      success. Controlled, randomized trials comparing sincalide or nothing, sincalide
      or a sphincterotome, or sincalide or glide or guide wire in patients in whom
      initial attempts to obtain a cholangiogram are unsuccessful are warranted.

PMID- 9252847
TI  - Ultrasonography-secretin test pattern after acute administration of octreotide in
      healthy persons and in patients with recurrent acute pancreatitis.
AB  - The intravenous administration of octreotide stimulates sphincter of Oddi
      activity and impairs pancreatic flow into the duodenum. Postsecretin
      ultrasonography (US-S test) has revealed an increase in the caliber of the main
      pancreatic duct, which disappears in healthy persons approximately 10 minutes
      later as a result of the opening of the sphincter of Oddi and passage of
      stimulated fluids into the duodenum. We have assessed US-S test patterns after
      octreotide in healthy persons and in patients with recurrent acute pancreatitis.
      The study sample consisted of 16 participants: alcohol-abstinent, nonsmoking,
      healthy volunteers (four men, three women; mean age: 28 +/- 2.5 years) and nine
      patients with recurrent acute pancreatitis (six men, three women; mean age: 32.1
      +/- 7.1 years). All participants underwent measurement of the main pancreatic
      duct at 1-min intervals for 60 min after secretin stimulation (1 IU/kg
      intravenous bolus). On a different day the same persons had repeated US-S tests 1
      hour after administration of 0.1 mg octreotide intramuscularly. In both controls
      and patients with recurrent acute pancreatitis, octreotide administration induced
      an appreciable dilatation of the main pancreatic duct before secretin
      stimulation, and the caliber remained significantly increased throughout the
      duration of the test. These results suggest that a single administration of
      octreotide at the dose used (a) does not inhibit pancreatic secretion of basal
      and secretin-stimulated fluid within the first 60 min and (b) probably exerts an
      inhibitory effect on sphincter of Oddi relaxation. These findings warrant more
      intensive study given their therapeutic implications for acute pancreatic
      disease.

PMID- 9252848
TI  - Acute viral hepatitis E: clinical and serologic studies in Singapore.
AB  - Seroprevalence of hepatitis E is now documented in many countries around the
      world, but studies of its clinical manifestations and serologic course have been
      confined to endemic areas. We have prospectively evaluated the occurrence,
      evolution, and outcome of acute hepatitis E in our patients. Fifteen patients (11
      men, 4 women; median age: 41 years) were diagnosed to have acute, sporadic
      hepatitis E between July 1993 and January 1995; 10 of the 15 were followed up.
      Sera anti-hepatitis E virus (HEV) immunoglobulin (Ig)G and IgM antibodies and HEV
      ribonucleic acid in the blood and stool were tested at weeks 1 and 2; serial
      tests for hepatitis E antibodies and liver function were carried out at months 1,
      3, 6, 9, 12, and 18. Coinfection with hepatitis A and superinfection on chronic
      hepatitis B were found in 3 and 2 patients, respectively. One patient had
      transient passage of virus in the stool, but none was viremic. Eighty-seven
      percent of patients lost their IgM antibodies within 3 months, but anti-HEV IgG,
      once present, persisted throughout follow-up. All patients but one had complete
      recovery. A higher than reported level of alanine transaminase (mean: 28.5 times
      normal) and the lack of viremia during acute infection in our patients may be due
      to increased immune-mediated viral clearance.

PMID- 9252850
TI  - Hypoxic hepatitis caused by severe hypoxemia from obstructive sleep apnea.
AB  - Cardiac and circulatory failure are the main causes of hypoxic hepatitis. In a
      prospective study of 142 cases of hypoxic hepatitis collected during a 10-year
      period, we encountered two cases resulting from extreme arterial hypoxemia
      without congestive heart failure, cor pulmonale, or circulatory failure. Both
      patients were morbidly obese women admitted to the intensive care unit for
      carbonarcosis. Oxygen arterial saturation was very low, less than 35% in both
      patients, but there was no history of cardiac or respiratory failure and no
      clinical evidence of circulatory failure. Cardiac function, evaluated by isotopic
      scintigraphy, was normal. After the episode of hypoxic hepatitis, a diagnosis of
      obstructive sleep apnea was made clinically and confirmed by performing nocturnal
      oximetry, which showed multiple episodes of oxygen desaturation in both patients.
      Polysonography could be performed in one case and was typical of obstructive
      sleep apnea. Liver ischemia is the main mechanism leading to hypoxic hepatitis.
      More recently, the role of passive congestion of the liver has been emphasized.
      Arterial hypoxemia, however, is generally considered to be a minor factor. Our
      two cases support the hypothesis that severe arterial hypoxemia may lead to
      hypoxic hepatitis even in the absence of cardiac and circulatory failure.

PMID- 9252849
TI  - A 3-year pilot study with 1,25-dihydroxyvitamin D, calcium, and calcitonin for
      severe osteodystrophy in primary biliary cirrhosis.
AB  - We carried out a 3-year pilot study of 59 consecutive women with osteoporosis of
      primary biliary cirrhosis (PBC), allocating them to two groups according to the
      severity of bone demineralization assessed by means of dual-photon absorptiometry
      (DPA) of the lumbar spine, Group A (36 patients; bone mineral density [BMD] >
      0.800 g/cm2) received no treatment; group B (23 patients; BMD < 0.800 g/cm2) was
      treated as follows: oral 1,25-dihydroxyvitamin D (0.5 microgram twice a day for 5
      days) followed by a 1-month course with oral calcium carbonate (1,500 mg/day)
      +carbocalcitonin (40 UMRC intramuscularly three times weekly). This treatment was
      repeated every 3 months. The following parameters were assessed at baseline and
      every 12 months: DPA, serum and urinary minerals, serum parathyroid hormone
      (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D.
      During follow-up, 11 initially untreated patients whose BMD dropped below 0.800
      g/cm2 were switched to the treatment group (8 after 12 months and 3 after 24
      months). No significant changes were observed in either group for PTH, BGP, or
      vitamin D metabolites. Comparing patients who were always treated, those who were
      never treated, and those who switched to the treatment group (ever treated) in
      this 36-month period, the percentage of annual bone loss in the never-treated
      patients was significantly less (p < 0.002) than in the ever-treated patients,
      suggesting the presence of two subgroups in PBC patients; one with rapid bone
      loss and the other with slow bone loss. Moreover, in the ever-treated patients,
      ADFR (activate, depress, free, repeat) therapy resulted in an improvement in BMD
      (p < 0.05 compared with the value before therapy). We conclude that ADFR therapy
      is effective in the treatment of patients with PBC with severe osteodystrophy,
      despite no change in osteoblastic activity, although controlled, randomized
      studies are in order to confirm our data.

PMID- 9252851
TI  - Delayed presentation of esophageal perforation as a result of overtube placement.
AB  - The first use of an overtube to assist endoscopy was described more than 20 years
      ago. Since then a number of uses of overtubes have been described, but relatively
      few complications have been reported. We report a case of esophageal perforation
      caused by overtube insertion during endoscopic band ligation of varices. This
      case is unique in that the patient presented 13 days after the original
      procedure, and it is the first reported case of esophageal injury involving the
      modified Bard overtube. The existing literature involving overtube injury is also
      reviewed.

PMID- 9252852
TI  - Cyclic neutropenia in Crohn's ileocolitis: efficacy of granulocyte colony
      stimulating factor.
AB  - A 40-year-old patient with long-standing Crohn's ileocolitis in remission
      experienced cyclic neutropenia with a periodicity of 14 days. He was not
      receiving immunosuppressive or myelosuppressive therapy. The patient had
      Staphylococcus aureus bacteremia resulting from central catheter infection, which
      was refractory to antibiotic therapy during the period of severe neutropenia.
      When granulocyte colony-stimulating factor (G-CSF) was administered, the cyclic
      neutropenia rapidly disappeared, the neutrophil and leukocyte counts normalized,
      and the sepsis resolved. When G-CSF therapy was discontinued, the leukocyte and
      absolute neutrophil counts again declined. With reinstitution of therapy, the
      leukocyte and absolute neutrophil counts recovered and normalized. Crohn's
      ileocolitis remained in remission during G-CSF therapy. This report confirms and
      extends one previous report of cyclic neutropenia associated with Crohn's disease
      and demonstrates in one patient the efficacy and safety of G-CSF on the
      hematologic, bacteriologic, and clinical manifestations of cyclic neutropenia
      associated with Crohn's disease.

PMID- 9252853
TI  - Splenic rupture after colonoscopy.

PMID- 9252854
TI  - Rectal bleeding from a mucous fistula secondary to a Dieulafoy's lesion.
AB  - Dieulafoy's lesion is a submucosal artery associated with a minute mucosal
      defect, and it is an extremely rare cause of profuse but intermittent
      gastrointestinal bleeding. Most cases have occurred in the proximal stomach
      within 6 cm of the gastroesophageal junction. Less commonly, cases are
      encountered in the antrum, duodenum, jejunum, colon, and rarely the rectum. Only
      three cases of rectal Dieulfoy's lesion have been reported in the English medical
      literature: one in a child and two in otherwise healthy young men. We report a
      case of a rectal Dieulafoy's lesion in an elderly man with a mucous fistula.
      Successful treatment was administered with a combination of injection therapy and
      heater-probe coagulation followed by elective surgical oversewing. Rectal
      Dieulafoy's lesions should be included in the differential diagnosis of
      unexplained rectal bleeding in the elderly.

PMID- 9252855
TI  - Massive gastrointestinal bleeding from a Dieulafoy-like lesion of the rectum.

PMID- 9252857
TI  - Severe hepatotoxicity on beginning propylthiouracil therapy.
AB  - We report a case of propylthiouracil (PTU)-induced cholestatic hepatotoxicity in
      Graves' disease that developed 1 day after beginning PTU. After clinical recover,
      liver abnormalities persisted for 5 years. Percutaneous liver biopsy and the
      eventual normalization of enzyme levels excluded permanent liver damage as a
      result of PTU therapy. Thus prolonged elevation of serum enzymes is consistent
      with the diagnosis of PTU-induced hepatotoxicity, which may recover completely.

PMID- 9252856
TI  - Pyrazinamide-induced granulomatous hepatitis.
AB  - Noncaseating granulomatous hepatitis may be caused by a variety of drugs, but we
      have not found, by computer search of the literature, a previous describe of
      granulomatous hepatitis associated with pyrazinamide. We describe a 52-year-old
      man with hectic fever, chills, extreme fatigue, liver damage, and hyperuricemia
      about 4 weeks after commencing pyrazinamide therapy. A liver biopsy specimen
      showed noncaseating epithelioid granulomas. The patient recovered soon after the
      interruption of tuberculostatic treatment.

PMID- 9252858
TI  - Primary biliary cirrhosis and gastric carcinoid: a rare association?
AB  - Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune
      disorders. Although antibodies against gastric parietal cells are found in nearly
      all PBC patients, autoimmune gastritis is only very rarely associated. We
      describe a woman with PBC in whom chronic autoimmune gastritis complicated by a
      large pedunculated gastric carcinoid tumor was found. Additionally, the patient
      had autoimmune thyroiditis. This was interpreted as the rare association of PBC
      with Schmidt's syndrome type III. The carcinoid tumor was removed endoscopically.
      We conclude from the case that an endoscopic screening for autoimmune gastritis
      should at least be performed in patients with PBC and autoimmune thyroiditis,
      keeping in mind the possible occurrence of a polyendocrinopathy and the
      potentially serious complication of a gastric carcinoid tumor.

PMID- 9252859
TI  - Idiopathic thrombocytopenic purpura in a liver transplant recipient with previous
      primary biliary cirrhosis.
AB  - The loss of immunotolerance has been implicated in the pathogenesis of both
      primary biliary cirrhosis (PBC) and idiopathic, immune-mediated thrombocytopenic
      purpura (ITP). An association between these two autoimmune diseases has been well
      described. We describe a 41-year-old woman in whom ITP developed 457 days after
      liver transplantation for PBC while receiving immunosuppressive medications
      sufficient to maintain allograft function. Our case report, the first to describe
      post-transplant ITP in association with PBC, demonstrates the persistence of the
      underlying immune dysregulation of PBC after transplantation. The practice of
      decreasing the dosage of immunosuppressive medication to maintenance levels after
      transplantation may unmask the effects of this defect in immunotolerance.

PMID- 9252860
TI  - Peritoneal mesothelioma in recurrent familial peritonitis.
AB  - A 39-year-old man had a 2-year history of fatigue, weight loss, drug-resistant
      ascites, and decreased intestinal motility. During adolescence he began to suffer
      frequent episodes of acute benign peritonitis that spontaneously subsided at age
      35. The fact that his younger brother was taking colchicine for the same symptoms
      led us to diagnose familial Mediterranean fever (FMF). The medical workup
      revealed uniform thickening of the intestinal wall with no signs of amyloidosis.
      Exploratory laparotomy revealed diffuse peritoneal mesothelioma that proved to be
      unresponsive to chemotherapy. There was no history of asbestos exposure. It is
      probable that the chronic peritoneal inflammation was responsible for the
      development of this tumor, although in almost all cases of FMF this phenomenon
      causes only limited peritoneal fibrosis or, less commonly, encapsulating
      peritonitis. A computerized search of the literature indicates that this is the
      second report of peritoneal mesothelioma associated with FMF.

PMID- 9252861
TI  - Gastrointestinal autonomic nerve tumor with giant abscess. A case report and
      literature review.
AB  - We report a gastrointestinal autonomic nerve tumor of the stomach with a giant
      abscess. The patient had fever and pain and was found to have anemia and an
      abdominal mass. X-ray and endoscopic examination showed a gastric submucosal
      tumor with a fistula to the gastric lumen. Partial gastrectomy was performed and
      no metastasis was found. On gross examination, the excised tumor was seen to be a
      submucosal solid tumor with a giant abscess. Alpha streptococci and anaerobic
      gram-negative rods were cultured from the pus of the abscess. The tumor resembled
      a gastric myogenic tumor composed of spindle cells, partly showing storiform and
      epithelioids. Tumor cells showed positive staining for vimentin and neuron
      specific enolase but were negative for desmin, alpha-smooth muscle actin, and S
      100 protein. Ultrastructural examination showed remarkable interdigitation of
      cytoplasmic processes with neurosecretory granules between the tumor cells. This
      lesion was similar to previously described gastrointestinal autonomic nerve
      tumors. Gastrointestinal autonomic nerve tumors are a rare, distinct subtype of
      gastrointestinal stromal tumors; although several cases of focally necrotic
      tumors have been reported, there has been only one report of the tumor with an
      abscess, as in our case.

PMID- 9252862
TI  - Crohn's disease and the myelodysplastic syndrome.

PMID- 9252863
TI  - 5-Aminosalicylic acid, 1,000-mg caplets versus 500-mg tablets, in maintenance of
      remission in ulcerative colitis.

PMID- 9252865
TI  - Malignant transformation in a duodenal villous adenoma of the afferent limb of
      Billroth II anastomosis.

PMID- 9252866
TI  - Successful endoscopic relief of large bowel obstruction in a case of a sigmoid
      colon gallstone ileus.

PMID- 9252864
TI  - Duodenal stenosis may not regress after eradication of Helicobacter pylori.

PMID- 9252867
TI  - Liver biopsy as a cause of Streptococcus bovis peritonitis.

PMID- 9252868
TI  - Did Alexander the Great die of acute pancreatitis?
AB  - I propose that Alexander the Great died of acute pancreatitis secondary to heavy
      alcohol consumption and a very rich meal. The cause of death of prominent
      historic or artistic figures attracts considerable interest of historians and
      researchers. This is especially the case for Alexander the Great. More than
      20,000 publications, books, or monographs on the life and work of Alexander the
      Great have been published. There are several theories and hypotheses regarding
      the cause of his death, that are based on historic descriptions, diaries,
      notations, and interpretations of events. It is inevitable that history and myth
      intermingle in any investigative approach, no matter how scholarly. In this
      article, on the basis of several historic sources. I have made an effort to
      reconstruct the final 14 days of his life and record the course of medical events
      that preceded his death with the formulation of a plausible diagnosis.

PMID- 9252869
TI  - Convenience store gastroenterology.

PMID- 9252870
TI  - AL-type amyloidosis presenting with rapidly deteriorating liver involvement.

PMID- 9252871
TI  - IL-4 as a key factor influencing the development of allergen-specific Th2-like
      cells in atopic individuals.
AB  - In the last years Th2-like cells, able to produce IL-4, IL-5, IL-6 and IL-10,
      have been shown to play an important role in the pathogenesis of allergic
      diseases. They are absolutely required for IgE production by B-cells and are
      expanded at the level of target tissues of atopic patients. Very recently, much
      attention has been focused on the genetic and environmental factors responsible
      for the differentiation and ongoing expansion of allergen-specific Th2-like cells
      in atopic subjects. In this review possible cellular sources of IL-4 in the
      primary, secondary and ongoing responses to allergens are discussed. In atopics,
      Th cell precursors themselves could be proposed as a main source of IL-4 in the
      primary responses to allergens. However, there is extensive evidence for the role
      of other cells such as mast cells, basophils and eosinophils as important sources
      of IL-4 the secondary and ongoing responses to allergens.

PMID- 9252872
TI  - Nonfatal systemic reactions to subcutaneous immunotherapy: a 10-year experience.
AB  - The present retrospective study reviews our clinical experience with Subcutaneous
      immunotherapy (SIT) over a 10 year period (1981-1991), in order to assess both
      incidence and clinical features of nonfatal systemic reactions due to this
      treatment. 192,505 injections were globally administered to 2,206 outpatients,
      following the suggested precautionary guidelines. We observed 115 systemic
      reactions (5.2% of patients and 0.06% of injections) and no fatalities. The
      association asthma + urticaria was the most frequent reaction (67%), followed by
      asthma alone (22%). No risk factor related to age, gender, pollen season or
      manufacturer was observed. The occurrence of systemic reactions was highly
      frequent in asthmatic patients, but approximately 1/3 of the patients who
      presented reactions had never previously suffered from asthma. The largest part
      of the observed reactions occurred during the maintenance phase of treatment.
      Almost all adverse events occurred within 30 minutes after the injection and they
      were promptly controlled by routine therapy. We conclude that subcutaneous
      immunotherapy, if performed with careful compliance to good clinical practice
      rules, is a safe treatment for respiratory allergy.

PMID- 9252874
TI  - Drug allergy: identification and characterization of IgE-reactivities to aspirin
      and related compounds.
AB  - Twenty-seven patients with aspirin (ASA) sensitivity were studied. 14 patients
      had naso-ocular-bronchial reactions after taking ASA while others had cutaneous
      and gastrointestinal reactions. The oral challenges with salicylic acid (SA), O
      methylsalicylic acid (OMSA), ASA, and the determination of IgE antibodies
      specific to salicyloyl, O-methylsalicyloyl, acetylsalicyloyl using correspondent
      disks by RAST, RAST inhibition and RAST crossinhibition assays were performed.
      The findings suggest that OMSA seems to be the main offender responsible for
      cutaneous and gastrointestinal reactions, whereas ASA is responsible for naso
      ocular-bronchial reactions. The clinical crossreactions between ASA and ASA-like
      drugs (nonsteroidal anti-inflammatory drugs and pyrazolone drugs) are probably
      due to "inborn errors of metabolism". The results indicate that genetic factors,
      mast-cell heterogeneity, and the interindividual variability in drug metabolism,
      combined with immunological background should be considered as underlying
      mechanisms.

PMID- 9252873
TI  - Skin manifestations and immunological parameters in childhood food allergy.
AB  - According to Hansen's contact rule, the digestive system should be considered as
      the main shock organ, yet in food allergy, this is not the case. Very often
      specific food triggers clinical manifestations not involving the digestive
      system; that is, reactions are manifested either in the respiratory system, as
      asthma or rhinitis, or in the skin. In these cases the BALT (broncho-alveolar
      lymphoid tissue) and GALT (gastrointestinal lymphoid tissue) units play a basic
      role in the sensitizations. The purpose of this study was to determine the most
      frequent skin manifestations of food allergy among children, and the most
      frequently involved foods. We also thought it interesting to evaluate the
      diagnostic reliability of the different standard immunological parameters
      utilized by the study team in food allergy. All patients underwent intracutaneous
      tests with 12 groups of the most frequent food allergens, as well as serum IgE,
      antigen-specific IgE against foods, and antigen-specific histamine release tests.
      Antigen-specific IgG4 determination was performed in some cases. The results
      obtained confirmed previous studies, the most common manifestations being:
      angioedema (48%), followed by urticaria (31%) and atopic dermatitis (21%).
      Regarding the frequency of sensitization to different food allergens, in mono- or
      polisensitization, fish and egg stand out in our environment. Certain food
      allergens are more frequently responsible for specific skin manifestations. Thus,
      for fish sensitization, the most frequent skin manifestation is atopic dermatitis
      (50%); for egg sensitization, angioedema is the most frequent skin manifestation
      (50%); and for milk, urticaria (50%). Finally, and in agreement with previous
      works regarding the diagnostic reliability of in vitro techniques, we found that
      the histamine release test offered the highest percentage of diagnostic
      reliability. Only for sensitization to milk proteins did antigen-specific IgE
      demonstrate higher reliability. Once again, we stress that our main problem is
      the lower reliability of skin tests against food allergens than against inhalant
      allergens. We emphasize the importance of food as a major factor in the
      etiopathogenesis of atopic dermatitis, as well as the need to complement the
      study, when possible, by means of the in vitro techniques described.

PMID- 9252875
TI  - Specific IgE to castor bean (Ricinus communis) pollen in the sera of clinically
      sensitive patients to seeds.
AB  - Human sensitization to castor bean seeds in occupational workers and people
      living close to oil processing factories has been acknowledged for a long time.
      In view of the cross-reactivity among different plant parts of the same species,
      we studies crossreactivity between seeds of castor bean and its pollen at the
      molecular level. Sera from 26 seed-positive atopics, when analyzed for ELISA
      against seed and pollen extracts of castor bean, showed binding with both seed
      and pollen extracts, but binding was stronger with seed extracts as compared to
      pollen. ELISA inhibition revealed partial similarity as pollen extract could not
      achieve 90% inhibition even at 100 micrograms/ml, and remained the same after
      protein concentrations of 40 micrograms/ml. Antigenic extracts of seeds and
      pollen separated into 12 and 20 fractions on SDS-PAGE, respectively. The 26 sera
      studied for specific IgE binding to different fractions of seed and pollen
      extracts showed IgE binding in 17 and 16 cases respectively, but with weak
      binding to pollen fractions. The crossreactivity was confirmed with pooled sera
      by blot inhibition. Seed antigen completely inhibited the sera for specific IgE
      at 10 mg/ml protein while pollen antigen showed only partial inhibition.
      Crossreactivity and presence of common epitopes between seed and pollen extracts
      are confirmed.

PMID- 9252876
TI  - Endoscopic scoring system in patients with allergic rhinitis.
AB  - Visual inspection of the airways in patients with chronic bronchitis and asthma
      by fiberoptic bronchoscopy and the relation of these findings to bronchoalveolar
      lavage (BAL) fluid analysis or some clinical parameters have been reported
      previously. In this study, we have attempted to assess and grade airway
      inflammation in allergic rhinitis patients (ARP) by fiberoptic bronchoscopy.
      During the procedure, BAL was obtained and visual inspection of airways done by
      the method used by Thompson et al. Ten ARP with bronchial hyperreactivity (BHR)
      (Group 1), 10 ARP without BHR (Group 2) and 2 nonatopic, healthy subjects
      (Control Group) were studied. The fluid recovery and differential cell
      concentration were similar in the three groups. The inflammatory scores were 11.0
      +/- 7.0, 13.8 +/- 6.9, 15.0 +/- 4.2 in group 1, group 2 and control group,
      respectively, without showing any significant differences between the groups.
      There was no correlation between the inflammatory score and PC20 to methacholine.
      This indicates that BHR in ARP will need explanations other than the inflammation
      within airways.

PMID- 9252878
TI  - Comparison among delayed-type skin tests, serum IgE levels and peripheral blood
      CD4 in HIV-positive patients.
AB  - Three groups of HIV-positive men and a control group of healthy subjects were
      evaluated simultaneously by delayed-type skin tests with recall antigens
      detection of CD4 cell counts in peripheral blood and the IgE serum levels.
      Delayed-type skin test reactivity and CD4 cell counts in peripheral blood
      decreased while IgE serum levels increased as immune imbalance progressed with
      the worsening of HIV infection (p = 0.003 between controls and HIV-positive
      patients). The existence of atopy did not significantly influence IgE serum
      levels in the groups of HIV-positive patients (p < 0.2). Candidin appeared as a
      useful antigen in the delayed-type skin tests considering that it was the only
      antigen that remained positive with low values of CD4 cell counts (< or =
      250/mm3). The detection of serum IgE levels as well as the performance of delayed
      type skin tests with recall antigens are useful tools to evaluate immunological
      status whereas the number of CD4 in peripheral blood is critical for determining
      the initiation of antiretroviral therapy.

PMID- 9252877
TI  - Annual and diurnal incidence of Cladosporium conidia in the atmosphere of
      Cordoba, Spain.
AB  - The presence of Cladosporium conidia in the atmosphere of Cordoba, a city in
      Southern Spain, was studied. Samplings were carried out over a three-year period
      in the form of hourly analyses by use of a Hirst volumetric inert collection
      medium trap, located 15 meters above ground level. The results obtained suggest
      that conidia from species of this genus are present in the atmosphere of Cordoba
      throughout the year. The mean of the concentrations obtained during the study
      period was 1065 conidia/m3 day. The conidium concentration show a markedly
      seasonal variation pattern, with two annual peaks (one in June and the other in
      September-October). The incidence of Cladosporium conidia in Cordoba appears to
      be determined mainly by the temperature and relative humidity. As regards
      intradiurnal variation, the number of Cladosporium conidia peaks between 8 and 10
      pm, with a minimum between 5 and 6 am.

PMID- 9252879
TI  - High-resolution computed tomography in patients with bronchial asthma:
      correlation with clinical features, pulmonary functions and bronchial
      hyperresponsiveness.
AB  - The high-resolution computed tomography (HRCT) studies for bronchial asthma (BA)
      have revealed abnormal radiologic findings such as bronchial wall thickening,
      bronchiectasis, emphysema and mosaic pattern of lung attenuation. But the
      clinical significance of these findings are not yet clarified. In this study, we
      quantified the bronchial wall thickness and evaluated HRCT features in 57 BA
      subjects (338 bronchi) who had precipitating factors of irreversible airway
      remodeling, 19 COPD subjects (70 bronchi) and 10 healthy subjects (23 bronchi).
      Then we correlated HRCT findings with the clinical features, pulmonary functions
      and methacholine PC20 (PC20M) and studied their clinical significance. The
      bronchial wall for BA was about 1.48 mm thicker than that for COPD and about 2.34
      mm thicker than for healthy controls (p < 0.0001, respectively). But the
      individual mean ratio of bronchial wall thickness to luminal diameter (BWT/LD) in
      asthmatics did not correlate with the clinical features, lung functions and
      PC20M. Abnormal HRCT findings, such as bronchiectasis (17.5%), emphysema (5.3%)
      and mosaic pattern of lung attenuation (17.5%) were found in BA. These findings
      were more common in BA with moderate to severe airflow limitation (FEV1 < 80%, p
      < 0.05) and patients with these changes had a more prolonged history of asthma (p
      < 0.05). PC20M was higher in BA with these abnormal changes (p < 0.001) but these
      patients' FEV1 (p < 0.05), FEF25-75 (p < 0.05) and specific airway conductance (p
      < 0.05) were lower than those having BA without such findings. In this study we
      showed that the bronchial wall was more significantly thickened in BA but that it
      did not correlate well with the clinical features, lung functions and PC20M.
      Additionally, patients having BA with abnormal airway and air space HRCT findings
      had a prolonged history of asthmatic symptoms, loss of lung functions and
      decreased bronchial hyperresponsiveness. These results suggested the possibility
      that HRCT can be used for the differentiation of BA from COPD or healthy
      controls. Furthermore, patients having BA with abnormal HRCT changes demonstrate
      poor lung function and less hyperreactive bronchi than those without. We
      concluded that HRCT may be useful for the prognosis and treatment of bronchial
      asthma cases who have the precipitating factors of irreversible airway
      remodelling.

PMID- 9252880
TI  - Recurrent fixed drug eruption caused by citiolone.
AB  - Citiolone (N-acetylhomocysteinethiolactone) is a thiolic-derived medication
      frequently used in Spain and in other countries as a mucolytic agent for the
      treatment of certain hepatic disorders. Mucolytic drugs have rarely been
      implicated in the fixed drug eruption etiology. We report on a patient who
      presented several episodes of fixed exanthema related to citiolone intake. The
      patch test with citiolone (10% in dimethyl sulfoxide) was negative. The diagnosis
      was confirmed by a positive controlled oral challenge test. Other mucolytic
      thiolic-derivatives (N-acetylcysteine) were tolerated by the patient, thus
      crossreactivity between these drugs seems to be unlikely.

PMID- 9252881
TI  - Coming out of the (water) closet.

PMID- 9252882
TI  - Breastfeeding research.

PMID- 9252883
TI  - Episiotomy.

PMID- 9252885
TI  - Continence for women: evidence-based practice.
AB  - Approximately 20% of women ages 25-64 years experience urinary incontinence. The
      symptoms increase during perimenopause, when 31% of women report that they
      experience incontinent episodes at least once per month. Bladder training and
      pelvic muscle exercise are the recommended initial treatment and can be taught
      effectively in the ambulatory care setting. Bladder training enables women to
      accommodate greater volumes of urine and extend between-voiding intervals. Pelvic
      muscle exercise increases muscle strength and reduces unwanted urine leakage.
      Accumulated research results provide evidence-based guidelines for nursing
      practice. The Association of Women's Health, Obstetric, and Neonatal Nurses has
      identified continence for women as the focus of its third research utilization
      project. This article presents the rationale, evidence base, and educational
      strategies compiled by the Research Utilization 3 Nurse Scientist Team. Nurses
      can enable women to incorporate these noninvasive techniques into self-care.

PMID- 9252884
TI  - Women's health.

PMID- 9252886
TI  - Immunologic adaptations during pregnancy.
AB  - Many complementary changes occur in a pregnant woman's immune system to protect
      the fetus from attack while maintaining maternal defenses against disease.
      Enhancements occur in immune elements that fight bacterial infections.
      Conversely, suppression of T-cell activity causes increased susceptibility to
      viral infections, such as hepatitis, rubella, herpes, and human papilloma virus,
      and leads to an irreversible reduction in helper T cells in women infected with
      the human immunodeficiency virus. Local secretion of corticosteroids and changes
      in cytokine concentration in the reproductive tract protect the fetus from
      rejection. Understanding these changes assists the perinatal nurse in assessing
      and counseling women of childbearing age.

PMID- 9252887
TI  - A smoking cessation plan for pregnant women.
AB  - Women continue to smoke during pregnancy for many reasons. Successful smoking
      cessation requires a comprehensive treatment approach. The proposed plan
      described in this article incorporates training for care providers; life skills
      support for clients; and ongoing, brief interventions. Prenatal visits provide
      the opportunity for these interventions. A smoking flow chart is used to
      facilitate continuity of message and consistent charting. Support for life
      skills, such as stress management, assertiveness, self-esteem, and role
      clarification, is integral to disrupting the cycle of addiction. Motivation of
      staff and smokers may be the nurse's most significant challenge. Further research
      into physiologic support, such as nicotine replacement, is recommended.

PMID- 9252888
TI  - Urinary tract infection during pregnancy: a risk factor for cerebral palsy?
AB  - OBJECTIVE: To assess a possible association of urinary tract infection (UTI)
      during pregnancy and cerebral palsy in offspring. DESIGN: Secondary analysis of a
      case-control study using structured telephone interviews and birth certificate
      reviews. SETTING: Cases from community-based agencies providing services to
      preschool children who were developmentally delayed. PARTICIPANTS: One hundred
      twelve preschool children with cerebral palsy and 153 children without cerebral
      palsy. MAIN OUTCOME MEASURES: Risk for cerebral palsy. RESULTS: The prevalence of
      UTI among case mothers was 17.9% compared with 5.2% among control mothers. The
      crude odds ratio for risk of cerebral palsy for a mother with a UTI was 3.9,
      whereas the adjusted odds ratio was approximately 5, indicating that the risk of
      having a child with cerebral palsy was 4 to 5 times greater for mothers who had a
      UTI during pregnancy. CONCLUSIONS: Urinary tract infection during pregnancy was
      found to be a risk factor for development of cerebral palsy in offspring.
      Assessment for UTI should occur at the initial prenatal visit and more frequently
      for women with symptoms or who are at risk. Pregnant women should be educated
      about preventive measures for UTI. Future research is needed to assess more
      directly the relationship between UTI during pregnancy and cerebral palsy in
      offspring.

PMID- 9252889
TI  - Bottle-feeding histories of preterm infants.
AB  - OBJECTIVE: To describe the bottle-feeding histories of preterm infants and
      determine physical indices related to and predictive of bottle-feeding initiation
      and progression. DESIGN: Ex post facto. SETTING: Academic medical center.
      PARTICIPANTS: A convenience sample of 40 preterm infants without concomitant
      cardiac, gastrointestinal, or cognitive impairment. MAIN OUTCOME MEASURES:
      Postconceptional age at first bottle-feeding, full bottle-feeding, and discharge.
      RESULTS: The morbidity rating, using the Neonatal Medical Index (NMI), was most
      strongly correlated with postconceptional age at first bottle-feeding (r = .34, p
      < .05), full bottle-feeding (r = .65, p < .01), and discharge (r = .55, p < .05).
      The morbidity rating also accounted for 12%, 42%, and 30% of the variance in
      postconceptional age at first bottle-feeding, full bottle-feeding, and discharge,
      respectively. CONCLUSIONS: The NMI may be a useful tool for predicting the
      initiation and progression of bottle-feeding in preterm infants.

PMID- 9252890
TI  - Bed rest from the perspective of the high-risk pregnant woman.
AB  - OBJECTIVE: To describe the experience of prolonged bed rest from the perspective
      of women during high-risk pregnancies. DESIGN: A focused ethnographic study that
      used interviews, participant diaries, and field notes as data sources. SETTING:
      Participants were obtained from an acute-care hospital antepartum unit and an
      antepartum home care program. PARTICIPANTS: Twenty-four women with complications
      of pregnancy requiring prolonged bed rest (range, 7-50 days). RESULTS: A model of
      the stress process in pregnant women on bed rest emerged from the data analysis.
      Stressors were grouped into situational (sick role, lack of control, uncertainty,
      concerns regarding fetus's well-being, and being tired of waiting), environmental
      (feeling like a prisoner, being bored, and having a sense of missing out), and
      family (role reversal and worry about older children) categories. Two main
      mediators of stress were social support and coping. Families, friends, and
      professionals were perceived as sources of support. Women used coping strategies,
      such as keeping a positive attitude, taking it 1 day at a time, doing it for the
      baby, getting used to it, setting goals, and keeping busy. Manifestations of
      stress were evidenced by adverse physical symptoms, emotional reactions, and
      altered social relationships. CONCLUSIONS: Prolonged bed rest is a stressful
      experience for pregnant women at high risk. Understanding the stress process in
      pregnant women confined to bed rest may assist nurses in developing interventions
      to reduce stressors and enhance mediators.

PMID- 9252891
TI  - Effects of social support on prenatal care and health behaviors of low-income
      women.
AB  - OBJECTIVE: To determine the relationship of social support from partners and
      others to the adequacy of prenatal care and to the prenatal health behaviors of
      low-income women. DESIGN: Descriptive, correlational study using self-reports and
      medical record review. SETTING: Data were collected in five metropolitan prenatal
      clinics serving low-income women. PARTICIPANTS: Ethnically diverse, primarily
      single, low-income pregnant women (N = 101) between 28 and 40 weeks of pregnancy.
      MAIN OUTCOME MEASURES: Subjects completed the Norbeck Social Support
      Questionnaire, the Prenatal Health Questionnaire, and the Demographic/Pregnancy
      Questionnaire. RESULTS: Social support provided by the partner correlated
      positively with adequacy of prenatal care, whereas social support from others
      (excluding partner relationships) correlated positively with prenatal health
      behaviors. Professionals such as health care providers and counselors were not
      considered sources of social support by women. CONCLUSIONS: Nurses who work with
      low-income pregnant women in a variety of settings should assist partners in
      recognizing their potential positive contributions, teach women to communicate
      their expectations to their partners, acknowledge the importance of other family
      members as providers of social support, and when needed, refer women to programs
      that increase available social support.

PMID- 9252892
TI  - Toward an understanding of addiction.
AB  - Given the large number of women with drug use and addiction problems, nurses have
      frequent opportunities to intervene to promote positive changes in drug use
      behavior. Classifications of drugs commonly used and terms relevant to drug use
      are presented. A discussion of different perspectives on addiction and a theory
      of change for addictive behaviors provides a foundation for working with women
      who have addictions.

PMID- 9252893
TI  - Addiction in women: prevalence, profiles, and meaning.
AB  - Biologic predisposition, stressors in the environment, and the extent and quality
      of social support in part explain the development of alcoholism and other drug
      dependencies in women. The nurse's approach to patients and use of effective
      tools for assessment of alcohol and drug use can result in increased
      identification and referrals for treatment.

PMID- 9252894
TI  - Drug treatment for women: traditional models and new directions.
AB  - Drug treatment is a diverse field in which a variety of treatment frameworks and
      formats exist, few of which have been tailored to women's circumstances and
      needs. Most drug treatment is based on insight-oriented and behavioral
      approaches, often accompanied by pharmacologic treatments. Complementary
      approaches such as acupuncture and biofeedback also are available. Feminist
      criticisms of traditional therapy have prompted development of woman-centered
      treatment, which provides a safe environment for empowerment and building
      relationship skills. Nurses can provide supportive interventions using mutuality
      and avoiding confrontation, and can advocate for access to woman-centered drug
      treatment and harm reduction measures to minimize the damage caused by alcohol
      and drugs.

PMID- 9252895
TI  - All my buddies was male: relationship issues of women with addictions.
AB  - There is a common perception that women who abuse drugs and alcohol do not like
      women. How does this attitude relate to women's abuse of drugs, and what
      difference might it make to the nursing care of addicted women. The importance of
      relationships to self and others has been emphasized in nursing theories, recent
      theories of women's psychologic development, and the social models used to
      explain substance abuse. This article examines what is known about the
      interpersonal relationships of women with addictions, including those with men
      and with other women, and explores how those relationships are associated with
      women's substance abuse behaviors. A brief explanation of current theories of
      women's psychologic development is followed by a review of the literature
      regarding the relationships of women with addiction problems, highlighting their
      attitudes toward themselves as women and the importance of the adult mother
      daughter relationship. Implications for the treatment of addicted women by nurses
      are discussed.

PMID- 9252896
TI  - In harm's way: childbearing women and nicotine.
AB  - In the United States cigarette smoking accounts for 11% of deaths of women.
      Approximately one of every four women smoke. Among pregnant women, 20-50% smoke,
      although prevalence rates vary depending upon income, age, and educational level.
      Spontaneous quit rates are highest among pregnant smokers. Interventions have
      been used to assist pregnant women to stop smoking, and the use of a combination
      of methods has yielded the highest quit rates among pregnant women, but
      postpartum relapse rates provide a glimpse of the short-term benefit of these
      intense efforts. Smoking cessation interventions for pregnant women must be
      considered within the larger context of women's lives to promote permanent
      smoking cessation.

PMID- 9252897
TI  - Malnutrition in children with cystic fibrosis: the energy-balance equation.

PMID- 9252899
TI  - Antineutrophil cytoplasmic antibodies in children with inflammatory bowel
      disease: prevalence and diagnostic value.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA), particularly
      perinuclear ANCA (p-ANCA), have been found more frequently in sera from patients
      with ulcerative colitis (UC) than in sera from Crohn's disease (CD) or
      unclassified enterocolitis (UE) patients. This 2-center study examined sera from
      102 pediatric patients with inflammatory bowel disease (IBD) to evaluate their
      diagnostic value and assess their relationship with disease features,
      distribution, activity and treatment. METHODS: The serum ANCA of 102 children
      with IBD were measured: 33 UC, 64 CD and 5 UE with various disease locations and
      degrees of activity. The mean age at the onset of symptoms was 10.7 years (1 to
      16.3 years). Sera from 26 unaffected first degree relatives and 20 children
      without IBD were also investigated. ANCA were detected using indirect
      immunofluorescence of ethanol-fixed granulocytes. RESULTS: There were ANCA in the
      sera of 24/33 children with UC (73%), 9/64 with CD (14%) and 4/5 with UE (80%). p
      ANCA were more frequent than cytoplasmic-ANCA in positive sera: UC = 67%, CD =
      57% and UE = 75%. The presence of ANCA was 73% sensitive and 81% specific for a
      diagnosis of UC, compared to other IBD (p < 0.001). Three children with proved
      sclerosing cholangitis associated with UC were all positive. There was no link
      between ANCA-positive sera and disease activity, or other endoscopic or clinical
      criteria. ANCA were detected in 4/26 first degree relatives (15%) and in 1/20
      control subjects (5%). CONCLUSIONS: Because of their sensitivity and specificity,
      ANCA may be helpful in the clinical assessment of patients with IBD, and
      especially those with UC. However, there is no link between the pressure of p
      ANCA and the site of UC or its activity, so that it cannot be used to monitor
      medical treatment or surgical indications.

PMID- 9252898
TI  - Experimental colitis impairs linear bone growth independent of nutritional
      factors.
AB  - BACKGROUND: Poor linear growth frequently complicates chronic inflammatory bowel
      disease in children. Circulating inflammatory mediators may play a role in this
      growth delay. We evaluated the effect of experimental colitis on bone growth in a
      nutritionally controlled rat model. METHODS: Experimental colitis was induced in
      male Sprague-Dawley rats (125-150 g) by enema with trinitrobenzene sulfonic acid
      in 50% ethanol on day 1 and 11 of a 14-day protocol. Control animals were pair
      fed and all animals received a liquid rat diet (1 kcal/ml). Twenty-four-hour
      urine, collected on days 2 and 12 and serum samples, collected at death, were
      analyzed for calcium, zinc, and magnesium. Serum samples from a separate set of
      animals were studied for serial interleukin-6 levels. Right proximal tibias were
      processed for growth-plate histomorphometry, in which linear growth is
      proportional to the heights of the proliferative zone, and terminal hypertrophic
      chondrocyte, but inversely proportional to the height of the resting zone.
      RESULTS: Histology confirmed active inflammation in the animals given
      trinitrobenzene sulfonic acid. Weight gain and both urinary excretion and serum
      levels of zinc, calcium, and magnesium did not differ between treatment and
      nontreatment groups. Histologically, there was impaired linear bone growth. The
      resting zone was greater in the colitis group (94.5 +/- 32.6 microns versus 3.9
      +/- 5.4 microns; p < 0.05); the proliferative zone was smaller in the colitis
      group (123.7 +/- 18.2 microns versus 78.9 +/- 11.2; p < 0.05 micron); the
      terminal hypertrophic chondrocyte was reduced in the colitis group (19.5 +/- 1.4
      microns versus 28.8 +/- 3.6 microns; p < 0.05). At 6 and 24 hours after
      induction, the level of interleukin-6 was elevated in the colitis group.
      CONCLUSIONS: Experimental colitis results in a decreased linear bone growth,
      independent of nutritional intake. Circulating cytokines derived from intestinal
      inflammation may contribute to the suppression of bone growth.

PMID- 9252900
TI  - Clinical outcome of ulcerative proctitis in children.
AB  - BACKGROUND: Although the course of ulcerative proctitis in adults has been well
      described, little data are available concerning its clinical behavior in children
      and adolescents. This study sought to characterize the presentation, response to
      therapy, and long-term course of ulcerative proctitis in the pediatric
      population. METHODS: A retrospective chart review was conducted at five pediatric
      gastroenterology centers. RESULTS: A total of 38 subjects (mean age 11.6 years)
      were identified with ulcerative proctitis (mean follow-up 4.3 years). Symptoms
      were mild at diagnosis in 74% and moderate or severe in 26%. Thirty-two percent
      had a complaint of constipation at presentation. Cessation of symptoms was noted
      in 68% within 3 months of therapy, an additional 24% within 6 months, and 8% were
      still symptomatic despite 6 months of therapy. During any subsequent yearly
      follow-up interval, -55% of patients were asymptomatic, 40% had a chronic
      intermittent course, and < 5% were continuously symptomatic despite therapy.
      Eight subjects were treated with oral corticosteroids, one with 6-mercaptopurine,
      and one with cyclosporine. Extension of inflammation proximal to the rectosigmoid
      occurred in 11 of 38 subjects (29%), 0.5-11.3 years postdiagnosis. Seven of the
      13 subjects (54%) followed for > or = 5 years had proximal extension of disease,
      and two had undergone colectomy. CONCLUSIONS: Despite a mild presentation in most
      subjects, ulcerative proctitis seems to have a high risk of proximal extension of
      disease. The overall response to therapy seems to be similar to that reported for
      ulcerative colitis in children. Follow-up endoscopic evaluation of patients with
      ulcerative proctitis seems warranted, especially in the setting of recurrent or
      recalcitrant symptoms.

PMID- 9252901
TI  - The 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth
      in children.
AB  - BACKGROUND: We evaluated the clinical utility of the 13C-xylose breath test for
      the diagnosis of small bowel bacterial overgrowth in children. METHODS: To
      determine the optimal dose of 13C-xylose, 29 healthy children, 3 to 12 years old,
      were randomly assigned to receive one of three doses of 13C-xylose (10, 25, or 50
      mg). After an overnight fast, the oral dose of 13C-xylose was administered, and
      breath samples were collected every 30 minutes for 4 hours. Samples were analyzed
      for 13CO2 by gas chromatography with mass spectrometry. Using the 50 mg dose, we
      then performed nine breath tests with concurrent duodenal bacterial cultures in 6
      children, 3 to 12 years old, with short-bowel syndrome (n = 2), immunodeficiency
      states (n = 1), and motility disorders (n = 3). RESULTS: Excretion of 13CO2 in
      breath peaked at 2.5 hours in all three control groups. The 50-mg dose produced
      the highest median peak and the smallest range of 13CO2 excretion in breath
      within each time period. The time of peak 13CO2 excretion in breath varied among
      the diseased children; however, the six patients with small-bowel bacterial
      overgrowth (2 x 10(5)-3.5 x 10(5) gram negative rods) all had peak 13CO2 that
      exceeded the maximum breath 13CO2 level in breath of the control subjects at the
      corresponding time period (100% sensitivity). Of the three patients with negative
      cultures, two had negative breath test results and one had positive results (67%
      specificity). One subject had normalization of both duodenal culture and breath
      test results after antibiotic treatment of small-bowel bacterial overgrowth.
      CONCLUSIONS: Our preliminary results suggest that with a dose of 50 mg 13C
      xylose, breath test results reliably predict small-bowel bacterial overgrowth in
      susceptible children.

PMID- 9252902
TI  - Plasminogen activation system in human milk.
AB  - BACKGROUND: Plasmin is the major endogenous protease present in milk. The level
      of plasmin activity is controlled by the availability of the precursor
      plasminogen and by the levels of plasminogen activators and inhibitors. Recently,
      a differential distribution of tissue-type plasminogen activator (t-PA) and
      urokinase-type plasminogen activator (u-PA) has been demonstrated in bovine milk.
      To assess whether this distribution pattern is a general feature, the occurrence
      of components of the plasminogen activation system in different fractions of
      human milk was investigated. METHODS: Milk samples were separated into the
      following fractions; milk fat, skim milk, and milk cells by centrifugation. The
      different fractions were detected for the presence of plasminogen and plasminogen
      activators by immunoblotting and zymography. The distribution of t-PA and u-PA
      was investigated by ligand binding analysis. t-PA-catalyzed plasminogen
      activation was examined by a coupled chromogenic assay. RESULTS: A differential
      distribution of plasminogen, t-PA, and u-PA was found. Casein micelles were found
      to exhibit t-PA and plasminogen binding activity, whereas the u-PA receptor was
      identified as the u-PA binding component in the cell fraction. Furthermore, human
      casein enhanced t-PA-catalyzed plasminogen activation, comparable to the
      enhancing effect obtained with fibrinogen fragments. CONCLUSION: The finding of a
      differential distribution of u-PA and t-PA in milk suggests that the two
      activators may have different physiological functions, which involve protection
      against invading microorganisms and maintenance of patency and fluidity in the
      ducts of mammary gland, respectively.

PMID- 9252904
TI  - Indices of body fat distribution in Spanish children aged 4.0 to 14.9 years.
AB  - BACKGROUND: Reference values for the main indices of body fat distribution in
      children are not available. METHODS: The study population comprised 1638
      Caucasian children and adolescents: 848 boys and 790 girls, with ages ranging
      from 4.0 to 14.9 years, and living in the central part of Spain (Provincia de
      Zaragoza). The waist-to-hip circumference ratio and the triceps-to-subscapular
      skinfold thickness ratio were measured. RESULTS: In boys, mean waist-to-hip
      circumference ratio ranges from 0.834, at 13.5 years, to 0.896 at 4.5 years. In
      girls, waist-to-hip circumference ratio ranges from 0.756, at 14.5 years, to
      0.877, at 4.5 years. We observed a decrease of waist-to-hip circumference ratio
      with age, especially in girls. In boys, triceps-to-subscapular skinfold thickness
      ratio ranges from 1.360, at age 14.5, to 1.704, at age 5.5. In girls, triceps-to
      subscapular skinfold thickness ratio ranges from 1.468, at age 13.5, to 1.727, at
      age 9.5. We observed a decrease with age only in boys. CONCLUSIONS: We present
      reference values for the main indices of body fat distribution, which could be
      useful in clinical practice. However, research is needed that will compare these
      indices with data on body fat distribution obtained by a gold standard method,
      such as computed tomography or magnetic resonance imaging.

PMID- 9252903
TI  - The effect of triglyceride positional distribution on fatty acid absorption in
      rats.
AB  - BACKGROUND: Human milk contains palmitic acid predominantly in the triglyceride
      sn-2 position, and differs from the palmitic acid positional distribution found
      in most infant formulas (predominantly positions sn-1 and sn-3). Following
      lipolysis by pancreatic lipase, 2-monoglycerides and free fatty acids are
      produced. All 2-monoglycerides are well absorbed, including 2-monopalmitin, thus
      providing one reason for the efficient absorption of palmitic acid in breast-fed
      infants. If infants are fed fat blends with palmitic acid located in the sn-1 and
      sn-3 positions, the resulting free fatty acids may form poorly absorbed calcium
      soaps. Therefore, many infant formulas contain only modest levels of palmitic
      acid. METHODS: Fat absorption studies were conducted in rats with preparations
      containing various amounts of palmitic acid in the triglyceride sn-2 position.
      Determining total fat absorption, specific fatty acid absorption, and the
      presence of calcium-fatty acid soaps. RESULTS: Betapol, a new triacylglycerol,
      similar to human milk in its palmitic acid content and positional distribution,
      demonstrated excellent absorption characteristics compared to fat blends derived
      from either palm olein or oleo (similar in fatty acid profile to Betapol, but
      with most palmitic acid in the sn-1 and sn-3 positions). A five-point dose
      response was used to further evaluate the relationship of positional distribution
      and fat loss. Palmitic acid excretion and fecal fatty acid soaps were negatively
      correlated to the presence of palmitic acid in the sn-2 position. CONCLUSION:
      These studies provide evidence that palmitic acid can be efficiently absorbed,
      avoiding fatty soap formation of it is present in the sn-2 position.

PMID- 9252905
TI  - Enteric cryptosporidiosis in pediatric HIV infection.
AB  - BACKGROUND: Enteric cryptosporidiosis is a frequent problem in adults with human
      immunodeficiency virus (HIV) infection, but little is known of its features in
      children. The aim of this study was to investigate the incidence and the clinical
      features of cryptosporidiosis in HIV-infected children. METHODS: Thirty-five
      children with symptomatic HIV infection were screened every 2 months, and in case
      of diarrhea, for the presence of Cryptosporidium. Intestinal function tests were
      performed, and the fecal osmotic gap was measured in children with
      cryptosporidiosis. RESULTS: Seventy episodes of diarrhea occurred in 16 children
      in a median period of 17 months. Cryptosporidium was detected in five cases, all
      with full-blown acquired immunodeficiency syndrome. Cryptosporidiosis was
      significantly more protracted than any other form of diarrhea and was associated
      with dehydration and severe weight loss. Intestinal function was not modified
      during cryptosporidiosis. Osmotic gap values were consistent with secretory
      rather than osmotic diarrhea. In four cases, recovery was observed without
      specific treatment. CONCLUSIONS: Enteric cryptosporidiosis is a severe problem in
      advanced stages of HIV infection. It does not induce intestinal malabsorption. It
      induces diarrhea of secretory type. Recovery may be observed independently of
      therapy.

PMID- 9252906
TI  - Insulin resistance with altered secretory kinetics and reduced proinsulin in
      cystic fibrosis patients.
AB  - BACKGROUND: Impaired glucose tolerance and secondary diabetes are frequent in
      older patients with cystic fibrosis (CF), associated with increased frequency of
      infections and reduced life expectancy. Studies on the pathophysiology of islet
      cell secretion in CF are a prerequisite for a scientifically based therapeutic
      approach. METHODS: Oral glucose tolerance tests were performed in 71 patients
      (14.2 +/- 0.5 years; mean +/- SE) and 56 control subjects (16.5 +/- 0.9 years).
      Glucose, insulin, C-peptide, and proinsulin were measured every 30 min. RESULTS:
      Glucose tolerance in CF patients was classified as normal (NGT, n = 48), impaired
      (IGT, n = 14), or diabetic (DM, n = 9). Even in CF patients with NGT, blood
      glucose was significantly elevated at 30, 60, and 90 min of the test.
      Surprisingly, the secretory responses of insulin and C-peptide were not reduced
      in CF patients with IGT or DM compared with both healthy controls or CF patients
      with normal glucose tolerance. However, peak insulin concentration was reached at
      90 min in CF-IGT or CF-DM patients compared with 30 min in controls. The ratio of
      glucose to insulin, an indicator of insulin resistance, increased in CF patients
      with progression of carbohydrate intolerance. Proinsulin was significantly
      reduced in all CF patients compared with controls (p < 0.001; Wilcoxon's rank sum
      test). CONCLUSIONS: In CF patients with impaired glucose tolerance or diabetes,
      integrated insulin release is not diminished, indicating that insulin resistance
      is likely to contribute to hyperglycemia in CF patients with IGT or DM. Reduced
      proinsulin levels in CF patients are compatible either with enhanced conversion
      of proinsulin to insulin in compensation for reduced beta-cell mass, or enhanced
      clearance of proinsulin.

PMID- 9252907
TI  - Activated eosinophils in esophagitis in children: a transmission electron
      microscopic study.
AB  - BACKGROUND: Esophagitis in infants and children is often characterized by
      eosinophilic inflammation. The underlying pathophysiologic mechanisms leading to
      this type of inflammation, and the role of eosinophils in the clinical expression
      of esophagitis, are unknown. The purpose of this study was to demonstrate the
      ultrastructural activation state of eosinophils in esophagitis in infants and
      children. METHODS: Standard transmission electron microscopy was used to examine
      endoscopic esophageal biopsy material from patients with and without esophagitis,
      as defined by standard histologic criteria. RESULTS: Twelve esophagitis and three
      control cases were studied. In patients with esophagitis, electron microscopy
      revealed numerous eosinophils throughout the mucosa and invariably demonstrated
      signs of activation, including inversion of core-to-matrix densities and lucency
      of granule core protein. Eosinophils in an activated state were seen in active
      diapedesis through vascular endothelium into the mucosa. Eosinophils were
      sometimes seen in proximity to lymphocytes. Biopsies of control patients did not
      demonstrate eosinophils. CONCLUSIONS: Eosinophils present in esophagitis are
      activated by electron microscopic criteria, and can been seen in an activated
      state entering into the mucosa. This suggests that eosinophils play an active
      role in the pathophysiology of this disorder, and that proinflammatory factors
      are present that selectively recruit and activate eosinophils in esophagitis in
      children.

PMID- 9252908
TI  - Use of cisapride in treatment of constipation in children.
AB  - BACKGROUND: Chronic constipation is a common problem in children. We observed the
      effects of cisapride in the management of idiopathic constipation in children.
      METHODS: Thirty-seven children with a history of constipation (i.e., pain and
      difficulty or delay in defecation for > 3 months) were recruited and randomly
      assigned to 8 weeks of treatment with either cisapride, 0.2 mg/kg three times
      daily, or matching placebo after a 2-week run-in period in a double-blind,
      parallel-group study design. In phase 1 (2 weeks), patients had plain abdominal
      radiographs to assess degree of faecal load, and those with impaction were given
      laxatives. After satisfactory clearance of faeces, total gastrointestinal transit
      time and orocaecal transit time were measured. In phase 2, after 8 weeks of
      treatment with either cisapride or placebo (0.2 mg/kg t.d.s.), the transit
      studies were repeated. RESULTS: Compared with placebo, cisapride did not improve
      either stool frequency or transit time in this study population. CONCLUSION: This
      study did not demonstrate a clinical role for the use of cisapride in the
      treatment of idiopathic constipation in children.

PMID- 9252910
TI  - Gastrointestinal cytomegalovirus infection complicating Crohn's disease in an
      adolescent without AIDS.

PMID- 9252909
TI  - Surgical therapy and follow-up of pancreatitis in children.
AB  - BACKGROUND: Acute and chronic pancreatitis in children differ from that in adults
      both from the etiology and the therapeutic approach. Within the frame of a blunt
      abdominal trauma-the most frequent cause in children-acute pancreatitis is often
      detected by emergency laparotomy and external drainage is recommended. Chronic
      relapsing pancreatitis, and particularly its hereditary form, is very rare in
      children and requires a different therapeutic concept. The results of surgical
      therapy for both forms of pancreatitis in childhood were evaluated in the present
      study. METHODS: Sixteen patients with acute and chronic relapsing pancreatitis
      were operated on in our facility between 1976 and 1988. Their history and
      postoperative course were analyzed in a retrospective study, including a final
      examination at the end of the follow-up period. RESULTS: Eight children with
      acute pancreatitis were operated on at an average age of 6 years and were
      followed up for an average of 7.5 years, with good results. The remaining
      children, aged between 3 and 14 years (average age of 9 years), were operated on
      for chronic relapsing pancreatitis. Our experience with early operative
      treatment, on average 2.7 years after onset of symptoms, is presented. Only three
      patients experienced a mild relapse during the follow-up period of 2-13 years
      (average of 5.4 years). CONCLUSIONS: For acute pancreatitis in childhood,
      operative treatment by inner drainage is necessary and effective only in case of
      complications, should conservative treatment fail. In children with chronic
      relapsing pancreatitis, the good exocrine and the normal endocrine function of
      the pancreas in these patients justified the early operation. Timely treatment is
      recommended in cases with typical changes of the pancreatic duct so as to shorten
      the relapsing clinical problems of the children and to maintain the function of
      the pancreas.

PMID- 9252911
TI  - Phytobezoar-induced ileal and colonic obstruction in childhood.

PMID- 9252912
TI  - Neonatal protein-losing enteropathy caused by intestinal lymphatic hypoplasia in
      siblings.

PMID- 9252913
TI  - Septicemia as a complication of Henoch-Schonlein purpura.

PMID- 9252915
TI  - Life-threatening food allergy in a child treated with FK506.

PMID- 9252914
TI  - Ovarian neoplasm and endometrioid carcinoma in a patient with Turcot syndrome.

PMID- 9252916
TI  - Oral insulin is biologically active on rat immature enterocytes.

PMID- 9252917
TI  - Disseminated nocardiosis complicating medical therapy in Crohn's disease.

PMID- 9252918
TI  - Recommended Dietary Allowances (RDAs), Recommended Dietary Intakes (RDIs),
      Recommended Nutrient Intakes (RNIs), and Population Reference Intakes (PRIs) are
      not "recommended intakes".

PMID- 9252919
TI  - Time for TNF?

PMID- 9252920
TI  - Breath hydrogen testing for small bowel bacterial overgrowth--a lot of hot air?

PMID- 9252921
TI  - Crohn's disease: to feed or not to feed at night is the question.

PMID- 9252922
TI  - Nutritional status in children with acute leukemia.

PMID- 9252923
TI  - Salmonella arizona enterocolitis acquired by an infant from a pet snake.

PMID- 9252925
TI  - Use of cisapride in treatment of idiopathic constipation in children.

PMID- 9252924
TI  - Correlation of hydrogen and methane production to rice carbohydrate malabsorption
      in Burmese (Myanmar) children.

PMID- 9252926
TI  - Thalidomide in oral Crohn's disease refractory to conventional medical treatment.

PMID- 9252927
TI  - Laparoscopic myomectomy. Time and cost analysis of power vs. manual morcellation.
AB  - OBJECTIVE: To compare electromechanical to manual morcellation in the performance
      of laparoscopic myomectomies. STUDY DESIGN: Laparoscopic myomectomy was performed
      with manual or electromechanical morcellation in a case-control study. Weight of
      myoma, patient weight and age were matched. Length of time for morcellation,
      blood loss, complications and length of hospital stay were measured. RESULTS:
      Twenty-eight cases of laparoscopic myomectomy, 14 with a manual and 14 with an
      electromechanical morcellator, were performed. Use of the electromechanical
      morcellator reduced the average time for extraction of myomas < 100 g by 15
      minutes and 401-500 g by 150 minutes on average. The average time savings for all
      myomectomies was 53 minutes. With operating room charges of $10 per minute, the
      $14,000 cost of the morcellator was recovered by the 21st case. CONCLUSION:
      Electromechanical morcellation results in significant time savings as compared to
      the manual technique. Financial savings accrue rapidly after the 21st case.

PMID- 9252928
TI  - Prophylactic cerclage in pregnancy. Effect in women with a history of conization.
AB  - OBJECTIVE: To evaluate the effect of prophylactic cerclage on the course of
      pregnancy in women with prior conization. STUDY DESIGN: In a retrospective,
      observational study, the outcome of pregnancies in 69 women with (n = 30) and
      without (n = 39) cerclage who previously underwent conization was evaluated
      regarding hospitalization due to threatened preterm labor and delivery before 37
      weeks of gestation. RESULTS: The occurrence of preterm delivery was 23.3% in the
      cerclage group and 20.5% in the control group (P = .78). Women with prophylactic
      cerclage were hospitalized significantly more often due to threatened premature
      labor: with cerclage, 66.7%; without cerclage, 33.3% (P = .006). CONCLUSION:
      Prophylactic cerclage should be used more sparingly in women with a history of
      conization because it does not prevent premature delivery and tends to induce
      preterm uterine contractions.

PMID- 9252929
TI  - Estrogen-androgen for hormone replacement. A review.
AB  - OBJECTIVE: To critically examine the role of androgens as part of postmenopausal
      hormone replacement therapy. STUDY DESIGN: Examination of original reports and
      reviews obtained by electronic database searches and supplemented by manual
      search of bibliographies. RESULTS: As compared to estrogens alone, estrogen
      androgen therapy may better protect against osteoporosis and increase libido,
      energy levels and general sense of well-being. However, estrogen-androgen
      replacement also reduces the beneficial increases in high-density lipoprotein
      induced by estrogens alone, although this effect may be offset at least partially
      by decreases in atherogenic triglycerides. The long-term net effect of estrogen
      androgen replacement on cardiovascular disease remains unknown. CONCLUSION:
      Although the literature includes relatively few clinical trials or well
      controlled studies and is further limited by the subjective nature of outcomes,
      such as sexual and psychological function, the available data suggest that for
      many postmenopausal women, estrogen-androgen replacement may provide benefits
      beyond those provided by estrogen-only replacement therapy.

PMID- 9252930
TI  - Cervex-Brush vs. spatula and Cytobrush. A cytohistologic evaluation.
AB  - OBJECTIVE: To compare the efficacy of two cervical smear instruments, Cervex
      Brush and spatula plus Cytobrush. STUDY DESIGN: Cervical smears were taken before
      laser ring biopsies in 213 women, who were randomized for the Cervex-Brush or
      spatula plus Cytobrush (S+C). The cytologic diagnosis was compared to the
      histologic diagnosis after laser ring biopsy. RESULTS: The correlation between
      cytology and histology showed comparable concordance (54% and 42%) for the two
      devices. In 130 (74 with Cervex-Brush and 56 S+C) patients, histology revealed
      moderate dysplasia or more advanced lesions. Those cases were further analyzed
      for smear failures. Negative smears were found in 13 cases (10 in the Cervex
      Brush and 3 in the S+C group). This difference in favor of S+C was not, however,
      statistically significant. Significantly more false negative smears were found
      when endocervical cells were absent and in patients 30-39 years of age.
      CONCLUSION: Modern sampling devices, such as the Cervex-Brush and S+C, seem to be
      equally efficient in obtaining dysplastic squamous cells. Other factors of
      importance for nonrepresentative cervical smears should be studied in order to
      improve efficacy.

PMID- 9252931
TI  - Previous cesarean birth. A risk factor for placenta previa?
AB  - OBJECTIVE: To study the risk of placenta previa following a previous cesarean
      birth. STUDY DESIGN: We conducted a population-based, case-control study using
      1990 North Carolina state birth certificate data. The study population included
      342 women with a pregnancy complicated by placenta previa and 1,082 randomly
      selected controls. Analysis was restricted to women who reported one or more
      previous live births and delivered a singleton, live neonate. Adjusted odds
      ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using
      logistic regression, controlling for maternal age, race, prior spontaneous or
      induced abortions and cigarette use. RESULTS: When the data were adjusted for
      maternal age, race, prior spontaneous or induced abortions, and cigarette use,
      women who had a previous cesarean birth and had a parity of 3 were 1.7 times more
      likely (OR 1.7, 95% CI 0.7, 4.2) and women of parity > or = 4 were 5.5 times more
      likely (OR 5.5, 95% CI 1.0, 30.1) to have placenta previa than women of parity 1
      who had a previous cesarean birth. CONCLUSION: Women with a history of a previous
      cesarean birth and parity > or = 3 were at increased risk of having a pregnancy
      complicated by placenta previa.

PMID- 9252932
TI  - Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral
      density and vasomotor symptoms. Nafarelin Study Group.
AB  - OBJECTIVE: To compare intranasal nafarelin and intramuscular leuprolide acetate
      (LA) depot in the management of endometriosis. STUDY DESIGN: A multicenter,
      prospective, randomized, double-placebo, double-blind study was conducted on
      subjects who had symptoms and signs of endometriosis and bone mineral density
      (BMD) within the age-appropriate normal range. For 6 months, 99 subjects received
      nafarelin, 200 micrograms twice daily, and placebo injections once monthly; 93
      subjects received LA depot injections, 3.75 mg once monthly, and placebo nasal
      spray, twice daily. Subjects were followed throughout treatment and for six
      months after treatment. The main outcome measures were changes in endometriosis
      symptoms and signs, BMD measurements, subject-reported and objectively measured
      hot flushes and circulating estradiol concentrations. RESULTS: Nafarelin was as
      effective as LA depot in alleviating symptoms and signs of endometriosis. LA
      depot recipients lost significantly more BMD, had more days with subjective hot
      flushes and more objectively measured hot flushes than did nafarelin recipients.
      In the nafarelin group, estradiol levels were consistently higher than in the
      leuprolide depot group, with significant differences by month 3 of dosing.
      CONCLUSION: Nafarelin and LA depot were equally effective despite higher
      estradiol levels in nafarelin recipients. Nafarelin-treated subjects lost less
      BMD, had fewer days with hot flushes and had fewer objectively measured hot
      flushes.

PMID- 9252933
TI  - Complete androgen insensitivity syndrome. Molecular characterization in two
      Chinese women.
AB  - OBJECTIVE: To study the molecular basis of complete androgen insensitivity
      syndrome (AIS). STUDY DESIGN: The coding region of the human androgen receptor
      (hAR) gene in two women with AIS was amplified with polymerase chain reaction
      using 12 pairs of oligonucleotide primers and then sequenced with a dye
      terminator method. RESULTS: Both patients had mutation in exon E of the androgen
      binding domain. In one patient, codon 732 GAC (aspartic acid) was changed to ACC
      (asparagine), and her CAG polyglutamine tract had 27 repeats. In the other
      patient, codon 765 GCC (alanine) was changed to ACC (threonine), and her CAG
      polyglutamine tract in exon A had 19 repeats. CONCLUSION: Except for CAG
      polyglutamine polymorphism, these two missense mutations were the only
      differences detected in the coding region of the hAR gene. Both mutations
      involved the CpG sequence, which has been regarded as a mutation hotspot. To the
      best of our knowledge, these two mutations have not been observed before in
      Chinese women. Elucidation of the molecular defects of AIS patients would be very
      helpful for genetic counseling and prenatal diagnosis.

PMID- 9252935
TI  - Laparoscopy for adnexal torsion in pregnant women.
AB  - OBJECTIVE: To report on six cases of adnexal torsion in pregnant women treated by
      operative laparoscopy. STUDY DESIGN: A retrospective study. Between January 1989
      and March 1996, 26 patients with adnexal torsion were treated by operative
      laparoscopy. Of these patients, six were pregnant (23%). The types of operative
      procedure and outcome were studied. RESULTS: Adnexal torsion occurred between 6
      and 13 weeks of amenorrhea. Two cases involved hyperstimulation, 3 cases a
      functional cyst and 1 case a dermoid cyst. In 4 cases laparoscopic treatment
      consisted of untwisting followed by puncture of the ovarian cyst; in 1 case it
      involved intraperitoneal cystectomy and in another simple untwisting of the
      adnexa. The immediate postoperative history was uncomplicated. In one patient
      with ovarian hyperstimulation, torsion recurred three weeks after the initial
      operation. No miscarriages occurred. CONCLUSION: In the hands of skilled
      surgeons, laparoscopy is well suited to the diagnosis and treatment of adnexal
      torsion occurring during the first trimester of pregnancy. Beyond 16 weeks or
      when there is any suspicion of torsion on a suspected tumor, it is preferable to
      use laparotomy.

PMID- 9252934
TI  - Impact of pregnancy on maternal AIDS.
AB  - OBJECTIVE: To assess the impact of pregnancy on maternal acquired
      immunodeficiency syndrome (AIDS) among tribal women in India. STUDY DESIGN: From
      February 1992 to February 1996, 71 tribal women from Manipur, India, with AIDS
      (Centers for Disease Control stage iii/iv), matched for age, parity, CD4
      lymphocyte count and demographic characteristics, were recruited into a
      prospective study. Thirty-two (49%) of these women were pregnant (8-10 weeks)
      (group A) and 38 (51%) nonpregnant (group B). RESULTS: Pneumocystis carinii
      pneumonia followed by miliary tuberculosis and wasting disease were the most
      common AIDS-defining illness and cause of maternal death in both groups. A total
      of 28 (39%) women died as a direct result of their AIDS-defining illness; 10
      (27%) of them were among the nonpregnant women as compared to 18 (56%) deaths
      among the pregnant women (P = .17, odds ratio 3.7285, 95% confidence interval
      1.23, 11.58). Three (16%) of these 18 deaths occurred within 14 weeks of an
      uneventful first-trimester medical termination of pregnancy. Thirteen women (41%)
      died undelivered at 30-34 weeks' gestation, and two died within 3 weeks of
      delivery. Fourteen (44%) women vaginally delivered 14 preterm infants, between 28
      and 35 weeks' gestation. Eleven of these infants died within six weeks; nine
      deaths were a direct result of prematurity and clinical diagnosis of an AIDS
      defining illness. The mean survival time was 9.72 months for the pregnant women
      and 22.6 months for the nonpregnant women (P = .066). CONCLUSION: Pregnancy
      increased maternal and fetal mortality in these AIDS-infected women.

PMID- 9252936
TI  - Simple ovarian cysts. Clinical features on a first-trimester ultrasound scan.
AB  - OBJECTIVE: To determine the clinical features of simple ovarian cysts, often seen
      on a first-trimester ultrasound scan. STUDY DESIGN: All initial examinations from
      patients scanned in 1993 (N = 1,001) were reviewed, and the clinical features of
      simple ovarian cysts were determined. Relationships were determined between the
      presence of a cyst and first-trimester pregnancy outcomes, including progression
      beyond the first trimester, blighted ovum, ectopic pregnancy and fetal demise.
      RESULTS: A simple ovarian cyst was observed in 29% of patients. Cysts were seen
      less often after 8 weeks' gestation, and there was an equal distribution between
      those on the right and those on the left side of the pelvis. Cyst diameters did
      not vary with gestational age, and most mean diameters were within a range of 1-3
      cm. The absence of a cyst was more often associated with a blighted ovum on
      follow-up ultrasound scan (relative risk, 2.8), but its presence or absence did
      not correlate with failure to progress beyond the first trimester, ectopic
      pregnancy or intrauterine fetal demise. CONCLUSION: The presence of simple
      ovarian cysts in the first trimester, which may represent corpus luteal cysts,
      appears to support early pregnancy development due to its association with a
      lower incidence of blighted ova.

PMID- 9252937
TI  - Spontaneous left tubal and right interstitial pregnancy. A case report.
AB  - BACKGROUND: Spontaneous bilateral ectopic pregnancy is a rare event and difficult
      to diagnose preoperatively. CASE: A unique case occurred of bilateral ectopic
      pregnancy involving the left fallopian tube and right cornu, or interstitial
      segment. CONCLUSION: This case demonstrates the difficulty in diagnosing
      heterotopic pregnancies and in particular those pregnancies with an interstitial
      component and also demonstrates the limits of ultrasound and laparoscopy in
      making such a diagnosis.

PMID- 9252938
TI  - Pregnancy after intracytoplasmic injection of immotile sperm. A case report.
AB  - BACKGROUND: With the advent of intracytoplasmic sperm injection (ICSI),
      fertilization and pregnancy have been reported in complete asthenozoospermia. The
      major problem with the use of immotile sperm for ICSI has been differentiating
      between live and dead sperm. We successfully selected live sperms with the
      hypoosmotic swelling test, and a twin pregnancy resulted after intracytoplasmic
      injection of completely immotile sperm. CASE: A 32-year-old woman and her 36-year
      old husband had had primary infertility for four years. Evaluation of the couple
      showed complete asthenozoospermia of the husband. Ovulation in the wife was
      successfully stimulated with clomiphene citrate, follicle-stimulating hormone and
      human menopausal gonadotropin. We selected the viable sperm with the hypoosmotic
      swelling test. ICSI was then performed. After assisted hatching, we transferred
      four embryos on the third day after oocyte retrieval. Intrauterine twin pregnancy
      was confirmed by ultrasonography four weeks later. The healthy infants, free of
      anomalies, were born on the 36th gestational week. CONCLUSION: The hypoosmotic
      swelling test is a simple method of selecting immotile and viable sperm for use
      in ICSI.

PMID- 9252939
TI  - Multiple gestation in a unicornuate uterus. A case report.
AB  - BACKGROUND: Uterine anomalies in the obstetric population have been reported to
      occur in 0.1-3.2% of patients, and the unicornuate uterus constitutes only 1-2%
      of these anomalies. CASE: A 35 year-old woman with known unicornuate uterus
      became pregnant with twins after controlled ovarian hyperstimulation and
      intrauterine insemination. The pregnancy was complicated by cervical
      incompetence, premature labor, dysfunctional labor, the need for cesarean
      delivery and postpartum uterine atony. CONCLUSION: This is the third reported
      successful outcome of multiple gestation following the use of assisted
      reproductive technologies in a patient with a unicornuate uterus. The presence of
      this mullerian anomaly should not be considered an absolute contraindication to
      the use of superovulation when treating infertility.

PMID- 9252940
TI  - Ruptured bacterial intracranial aneurysm in pregnancy. A case report.
AB  - BACKGROUND: Rupture of a documented infectious cerebral aneurysm is a rare
      complication of infectious endocarditis, with a high morbidity and mortality
      rate. The only previously reported case was associated with maternal and neonatal
      mortality. No known report exists of a ruptured bacterial intracranial aneurysm
      complicating an ongoing pregnancy with maternal or fetal survival. CASE: A 38
      year-old, white woman, gravida 9, para 4, at 18 weeks' gestation, developed
      infectious endocarditis with peripheral and cerebral emboli secondary to
      intravenous drug abuse, causing renal failure and cortical strokes. She required
      hemodialysis and also suffered a subarachnoid hemorrhage due to rupture of
      cerebral bacterial aneurysms. A team approach to her care was necessary. At 28
      weeks' gestation she delivered by cesarean section for abruptio placentae. Both
      the mother and neonate recovered. CONCLUSION: Rupture of mycotic aneurysms can be
      catastrophic and is often managed surgically. The patient described here was
      severely affected, and though indicated, surgical intervention was not possible.
      An aggressive team approach provided a good maternal and fetal outcome.

PMID- 9252941
TI  - Glutamine-supplemented nutrition.

PMID- 9252942
TI  - Epidermal growth factor up-regulates sodium-glucose cotransport in enterocyte
      models in the presence of cholera toxin.
AB  - BACKGROUND: Sodium-glucose cotransport by enterocytes is key to the successful
      implementation of oral rehydration in diarrhea. Confluent, differentiated Caco-2
      cells have enterocyte-like characteristics. We have previously shown that short
      term incubation of isolated rat jejunal enterocytes with epidermal growth factor
      (EGF) results in the up-regulation of sodium-glucose cotransport. The aim of this
      study was to examine the effect of EGF on Caco-2 cells in the presence of cholera
      toxin. METHODS: Caco-2 cells grown on tissue culture dishes were used for glucose
      and sodium uptake studies and cells were grown on polycarbonate membranes for
      transport examinations. Effects of EGF on the kinetic parameters of sodium
      glucose contransporter, thymidine transport, and on the activity of Na+/K(+)
      ATPase were examined. The efficacy of basolateral vs apical EGF on sodium and
      glucose transport was compared after incubation of the monolayers with 10 nmol/L
      of cholera toxin. RESULTS: EGF increased both glucose and sodium uptake and
      transport, and we observed a simultaneous increase in the activity of Na+/K(+)
      adenosine triphosphatase (ATPase). Kinetic studies performed on brush-border
      membrane vesicles prepared from EGF-incubated confluent monolayers and on intact
      cells showed an increase in the maximum velocity but not the Michaelis constant,
      suggesting increased availability of transporters rather than conformational
      change. This effect was seen within minutes in both of the two putative
      transporters, high-affinity, low-capacity and low-affinity, high-capacity. There
      was no acute effect on thymidine uptake. Studies in the presence of cholera toxin
      demonstrated a significant up-regulation in sodium-glucose cotransport when EGF
      was applied from the basolateral side; the increase was smaller but significant
      with apical application. CONCLUSIONS: Differentiated Caco-2 cells have two
      kinetically distinct sodium-glucose cotransporters. Short-term incubation of Caco
      2 cells with EGF resulted in an up-regulation of sodium-glucose cotransport and
      subsequent increase in Na+/K(+)-ATPase activity. The effect of basolaterally
      applied EGF was more significant with or without incubation with cholera toxin.
      The early effect of EGF on glucose and sodium cotransport may have important
      therapeutic implications in diarrhea and dehydration states. The in vitro model
      described here uses a homogeneous cell population and provides a versatile system
      for uptake and transport studies.

PMID- 9252943
TI  - 1997 Jonathan E. Rhoads Lecture. Understanding obesity: the unfinished business.

PMID- 9252944
TI  - 1997 Harry M. Vars Research Award. Does the route of feeding modify gut barrier
      function and clinical outcome in patients after major upper gastrointestinal
      surgery?
AB  - BACKGROUND: Direct experimental evidence suggests that total enteral nutrition
      (TEN) reduces septic morbidity compared with bowel rest and total parenteral
      nutrition (TPN) and that mucosal support and maintenance of gut barrier function
      is a key mechanism. This effect is supported indirectly by clinical studies, but
      this question has not previously been investigated directly in the postoperative
      patient. This study examined the hypothesis that early enteral feeding after
      major upper gastrointestinal surgery may modulate gut barrier function and
      decrease the risk of major infective complications compared with bowel rest and
      parenteral nutrition. METHODS: A randomized clinical trial of 67 patients (TPN =
      34; TEN = 33) fed postoperatively for 7 days was performed. Thirty-day major
      morbidity and mortality were monitored. Intestinal permeability was measured
      using the lactulose/mannitol test preoperatively and on postoperative days 1 and
      7. Systemic anti-endotoxin core immunoglobulin G and M antibodies and serum
      albumin and C-reactive protein were quantified at these time points. RESULTS: No
      clinical benefit was observed in patients fed enterally compared with the
      parenterally fed group. Intestinal permeability was increased on the 1st
      postoperative day in association with evidence of endotoxin exposure. By day 7,
      enteral feeding compared with parenteral feeding had failed to significantly
      influence any of the gut barrier or systemic parameters. CONCLUSIONS: This
      randomized controlled trial of TEN vs TPN after major upper gastrointestinal
      surgery failed to show a clinical benefit for the enteral route. Moreover,
      enteral nutrition did not modulate gut barrier function postoperatively.

PMID- 9252945
TI  - Early postoperative enteral nutrition improves peripheral protein kinetics in
      upper gastrointestinal cancer patients undergoing complete resection: a
      randomized trial.
AB  - BACKGROUND: Patients with upper gastrointestinal (GI) tract malignancies are at
      risk for malnutrition and postoperative morbidity and mortality. We examined the
      protein kinetic effects of early enteral feeding in this population and compared
      it with results in patients receiving IV fluid. METHODS: Twenty-nine patients
      undergoing resection of an upper GI tract malignancy were prospectively
      randomized to either enteral feeding starting on postoperative day (POD) 1 via a
      jejunostomy tube (FEED, n = 12) or IV fluid (IVF, n = 17). On POD5, all patients
      underwent a protein metabolic study using [3H]phenylalanine to determine forearm
      skeletal muscle (nmol phenylalanine/100 g/min) protein net balance. Free fatty
      acids (FFA, mEq/dL) and insulin levels (mU/mL) were measured. RESULTS: Protein
      net balance was significantly less negative in the FEED group compared with the
      IVF group (-1.4 +/- 0.8 vs -5.0 +/- 1.4, p < .05). Respiratory quotient was
      significantly increased in patients receiving enteral feeding (0.85 +/- 0.02 vs
      0.78 +/- 0.02 FEED vs IVF, p < .05). FFA levels were significantly decreased in
      the FEED group (0.36 +/- 0.04 vs 0.85 +/- 0.07, p < .05). Insulin levels were
      significantly elevated in the FEED group (19.8 +/- 4.5 vs 9.3 +/- 0.8, p < .05).
      Insulin levels correlated with amino acid fluxes. CONCLUSIONS: Postoperative
      enteral nutrition in upper GI cancer patients results in an improvement in
      protein kinetic net balance and amino acid flux across peripheral tissue. In
      addition, insulin levels are elevated, and this elevation correlates with amino
      fluxes across the forearm. By improving peripheral protein kinetics, early
      postoperative enteral nutrition may potentially contribute to a decrease in
      postoperative morbidity and mortality in upper gastrointestinal cancer patients.

PMID- 9252946
TI  - Glutamine-enriched enteral diet enhances bacterial clearance in protected
      bacterial peritonitis, regardless of glutamine form.
AB  - BACKGROUND: The effects of glutamine (Gln)-enriched enteral diets on bacterial
      clearance were investigated in a rat protracted peritonitis model. The effects of
      the Gln form, peptide-based vs free amino acid-based, were also compared.
      METHODS: Twenty-three rats underwent gastrostomy. An osmotic pump was implanted
      in the peritoneal cavity. The rats received a continuous intragastric infusion of
      one of three diets: Gln-depleted (Gln 0), Gln-enriched with the Gln in free amino
      acid form (Gln F), or Gln-enriched with the Gln in oligopeptide form (Gln P). The
      three formulas were isocaloric and isonitrogenous. The pumps delivered a
      continuous infusion of Escherichia coli, starting at 48 hours after implantation,
      for 24 hours. Then, the animals were killed. RESULTS: Bacterial numbers in
      peritoneal lavaged fluid (PLF) and the liver were significantly lower in the Gln
      P and Gln F groups than in the Gln 0 group. The bacterial number in PLF
      correlated with that in the liver. Neither the number nor the population of
      peritoneal exudative cells differed among groups. Plasma levels of proline,
      alanine and citrulline were significantly higher in the Gln P and Gln F groups
      than in the Gln 0 group. Both Gln supplemented groups showed significantly
      greater villous height, crypt depth, and numbers of mitoses per crypt in the
      small intestine than the Gln 0 group. CONCLUSIONS: Supplemental Gln enhances
      peritoneal and hepatic bacterial clearance, regardless of Gln form. Gln-enriched
      may be more beneficial than Gln-depleted enteral diets in peritonitis.

PMID- 9252947
TI  - Arginine-enhanced enteral nutrition augments the growth of a nitric oxide
      producing tumor.
AB  - BACKGROUND: Arginine-enhanced diets have been shown to be beneficial in tumor
      bearing hosts, but no data exist regarding their effects in hosts bearing nitric
      oxide (NO)-producting tumors. OBJECTIVE: To examine the effect of arginine
      supplementation on the growth of a NO-producing murine breast cancer cell line.
      METHODS: EMT-6 cells were grown in various concentrations of arginine in the
      presence or absence of the inducible nitric oxide synthase (iNOS) inhibitor,
      aminoguanidine (1 mmol/L). Forty-eight hours later, nitrite accumulation and
      viable cell number were assessed. BALB/c mice were then pair-fed basal purified
      diets (n = 10), 4% casein diets (isonitrogenous control, n = 5), or 4% arginine
      enhanced diets (n = 10). One week later, 10(5) EMT-6 cells were implanted
      subcutaneously into the dorsal flank. After tumor implantation, five mice fed
      basal purified diets and five mice fed arginine-enhanced diets also received
      aminoguanidine (100 mg/kg subcutaneously twice daily). Two weeks after tumor cell
      implantation, tumor size (mean diameter), animal weight, serum and tumor nitrite
      and nitrate levels were measured. RESULTS: There was minimal nitrite accumulation
      in arginine-free media, while increasing the arginine concentration increased
      nitrite levels. Viable cell number did not increase in arginine-free media, but
      increased nearly twofold in 100 and 1000 mumol/L arginine. In 5000 and 10,000
      mumol/L arginine, the difference in viable cell number was not statistically
      different than that seen in arginine-free media, whereas the addition of
      aminoguanidine blocked nitrite accumulation and increased viable cell number at
      these arginine concentrations. Arginine-enhanced diets stimulated tumor growth in
      vivo more than twofold over tumor growth in mice fed isonitrogenous control or
      basal purified enteral diets. Mice fed arginine-enhanced diets also had increased
      serum nitrite and nitrate levels over mice fed basal purified enteral diets,
      whereas tumors from mice fed arginine-enhanced diets had nitrite and nitrate
      levels similar to mice fed basal purified enteral diets. Aminoguanidine blocked
      the increase in serum nitrite and nitrate, but failed to block the increased
      tumor growth in mice receiving the arginine-supplemented diets. CONCLUSIONS:
      Arginine concentration influences the growth of EMT-6 tumor cells in vitro and
      dietary arginine supplementation augments tumor growth in vivo. The mechanism of
      the growth modulation in vitro is NO-dependent whereas the enhanced tumor growth
      in vivo is NO-independent.

PMID- 9252948
TI  - Effect of medium-chain triglyceride emulsion in total parenteral nutrition on
      experimental hepatic metastasis in the rat.
AB  - BACKGROUND: This study evaluated the effect of total parenteral nutrition (TPN)
      regimens containing a medium-chain triglyceride (MCT) emulsion on tumor
      metastasis. METHODS: Tumor metastasis development was assessed by the number of
      metastatic foci on the liver surface in rats inoculated with ACL-15 tumor cells
      via the portal vein. Rats received one of the following TPN regimens: TPN
      containing an MCT emulsion (group M), in which tricaprylin emulsion served as the
      MCT and comprised 50% of nonprotein calories (NPC); TPN containing a long-chain
      triglyceride (LCT) emulsion (group L), in which soybean oil served as the LCT and
      comprised 50% of NPC; and TPN without lipid emulsion (group G), in which dextrose
      comprised 100% of NPC. RESULTS: The number of metastatic foci was greatest in
      rats receiving TPN containing the MCT emulsion on day 11 after tumor cell
      inoculation and either 11 days of TPN or 2 days of TPN followed by 9 days
      standard rat chow. CONCLUSIONS: TPN containing MCT emulsion increases liver
      metastasis early in its administration.

PMID- 9252949
TI  - Triglyceride hydrolysis of soy oil vs fish oil emulsions.
AB  - BACKGROUND: Fish oil triglycerides (TG) are being considered for use in IV lipid
      emulsions, but the characteristics of their lipase-mediated clearance from plasma
      are largely unknown. METHODS: We compared the in vitro hydrolysis of soy oil long
      chain triglyceride emulsions (LCT) and fish oil emulsions (omega-3) using
      lipoprotein (LPL) and hepatic (HL) lipases, omega-3 emulsions contained 18% and
      28% of total TG fatty acid as eicosapentaenoic acid (EPA) and docosahexanoic acid
      (DHA), respectively. RESULTS: Under conditions of maximal hydrolysis, total free
      fatty acid (FFA) release was two- to threefold greater with LCT compared with
      omega-3 emulsions. Also, EPA and DHA together contributed proportionally much
      less than other fatty acids (< 20%) to FFA released from omega-3 emulsions. In
      mixtures of LCT emulsion with omega-3 emulsions, the presence of > 20% of omega-3
      particles substantially inhibited LCT emulsion hydrolysis (by up to 50%).
      CONCLUSIONS: Our results suggest that, during infusion of omega-3 emulsions, EPA
      and DHA may enter cells as TG or partial glycerides within emulsion particles and
      not as FFA and that coinfusion of omega-3 emulsion with LCT emulsion at low omega
      3:LCT emulsion ratios (up to 20% of total triglyceride as omega-3) will not
      substantially inhibit LCT hydrolysis.

PMID- 9252950
TI  - A prospective survey for central line skin-site colonization by the pathogen
      Malassezia furfur among hospitalized adults receiving total parenteral nutrition.
AB  - BACKGROUND: Over 50 case reports suggest that Malassezia furfur is an emerging
      systemic pathogen in neonates who receive IV lipid emulsions. Because isolation
      of this fungus requires special culture techniques, which are not routinely used,
      the authors of many case reports of M. furfur infections in adults question
      whether infections caused by this organism are being underdiagnosed in older
      patients. METHODS: Catheter insertion site colonization rates in adults receiving
      total parenteral nutrition (TPN) were prospectively evaluated in 149 hospitalized
      patients with 928 cultures handled specifically for M. furfur detection. Positive
      control samples consisted of M. furfur cultures in neonates and in adults, who
      had not been enrolled in the study, and of a separate positive culture obtained
      from a skin site inoculated with M. furfur. RESULTS: M. furfur was not cultured
      from any of the 928 study samples (95% confidence interval [CI] -0.4% to +0.4%).
      CONCLUSIONS: These results suggest that M. furfur is less of a threat to
      hospitalized adults receiving TPN than has been otherwise postulated. These data
      do not support the inclusion of special cultures for M. furfur in routine skin
      site surveillance programs among hospitalized adults receiving TPN.

PMID- 9252951
TI  - Pentoxifylline and thalidomide fail to reduce hepatic steatosis during total
      parenteral nutrition and bowel rest in the rat.
AB  - BACKGROUND: We suggested that the continuous translocation of endotoxin from Gram
      negative bacterial overgrowth during bowel rest and total parenteral nutrition
      (TPN) causes the release of tumor necrosis factor (TNF), resulting in liver
      damage and hepatic dysfunction. Because TPN-induced hepatic steatosis was
      significantly reduced by the monoclonal antibodies against TNF, we attempted a
      more clinically applicable approach using pentoxifylline and thalidomide.
      METHODS: A control group (group I) fed rat chow and four groups of rats receiving
      TPN were studied. Group II received TPN only; group III, TPN and 100 mg/kg/d
      pentoxifylline; group IV, TPN and 200 mg/kg/d pentoxifylline; and group V, TPN
      and 5 mg/kg/d thalidomide. On day 7, total liver fat was determined. RESULTS:
      Bowel rest and TPN resulted in a significant (p < .0005) increase in liver fat
      content that was unaltered by either pentoxifylline or thalidomide. CONCLUSIONS:
      Our results show no role for pentoxifylline or thalidomide in reducing TPN
      associated hepatic steatosis.

PMID- 9252952
TI  - Long-term central venous access through the ovarian vein.
AB  - This is a case report of a patient, totally dependent on parenteral nutrition,
      with thrombosis of the superior vena cava and infrarenal inferior vena cava. The
      ovarian vein was the most accessible route for placement of a long-term
      indwelling catheter. We describe a technique of central venous access via the
      ovarian vein through a lower midline laparotomy.

PMID- 9252953
TI  - Subcutaneously implanted enteral nutrition port.
AB  - BACKGROUND: Patients who have undergone esophagectomy with extensive lymph node
      dissection under thoracolapalotomy for advanced esophageal carcinomas frequently
      need long-term nutrition support because of their inadequate oral intake. We have
      used tube enterostomy feeding for these patients not only immediately after the
      operations but also at home to prevent the development of malnutrition. Patients
      who receive long-term tube enterostomy feeding often suffer from skin problems
      around the enteral nutrition catheters. Once the catheter is removed, the patient
      with anticipated malnutrition is subsequently unable to receive beneficial
      enteral nutrition. We have developed a new enteral access system that is placed
      subcutaneously. This subcutaneously implanted enteral nutrition port makes
      possible intermittent and long-term enteral nutrition support not only for the
      postoperative period but also for home care. METHODS: This system consists of the
      port (Infuse-a-Port, SMAP15 Snaplock Macro-Port Venous Access System; Strato
      Medical Co) and the enteral nutrition tube (Enteral Tube 8F, 75 cm; Zeon Co).
      This system was applied to seven patients who had undergone esophagectomy. The
      port was placed on the lower chest subcutaneously, and the catheter was placed
      through the gastric tube and duodenum up to the jejunum. After the operation, a
      20-gauge port needle was placed, and enteral nutrition formula (Enterued; Termo
      Co) was started with the enteral nutrition pump. RESULTS: No complications (eg,
      infection of skin, obstruction of tube) were observed from the postoperative
      period through the home care stage. The observation period for this implanted
      system ranged from 2 to 12 months. The patients were able to avoid the
      malnutrition anticipated after the extensive operations and continued to receive
      nutrition support safely and effectively at home. CONCLUSION: This new nutrition
      support system is safe and efficient for patients who anticipate long-term
      enteral nutrition support. A subcutaneously implanted enteral nutrition port
      makes possible intermittent and long-term nutrition support without patient
      discomfort and inconvenience.

PMID- 9252954
TI  - Testosterone replacement increases fat-free mass and muscle size in hypogonadal
      men.

PMID- 9252955
TI  - Essential fatty acid status in patients.

PMID- 9252956
TI  - Low fat-monounsaturated rich diets containing high-oleic peanuts improve serum
      lipoprotein profiles.
AB  - Postmenopausal hypercholesterolemic women are at risk for cardiovascular disease
      and are encouraged to follow low-fat (LF) (< or = 30% energy) diets. However,
      these diets may have undesirable effects on high density lipoprotein cholesterol
      (HDL-C), apolipoprotein A-I (apo A-I) and triglycerides, whereas diets high in
      monounsaturated fats do not. Twenty postmenopausal hypercholesterolemic women
      previously consuming high-fat diets (34% energy) were placed on a low fat
      monounsaturated rich diet (LFMR: 26%, 14% energy, respectively) for 6 men.
      Sixteen women already eating LF diets (24% energy) were also followed to monitor
      variations in serum lipids due to seasonal variations. Twenty-five women
      successfully completed the study (LFMR = 12, LF = 13). Serum cholesterol
      decreased 10% (264 to 238 mg/dL, P < or = 0.01) and low density lipoprotein
      cholesterol (LDL-C) decreased 12% (182 to 161 mg/dL, P < or = 0.01) in the LFMR
      group, but did not change in the LF group. The reduction in serum cholesterol in
      the LFMR group was greater than estimated by predictive formulas. Serum
      triglycerides and apo A-I did not change in the LFMR group. A modest decrease in
      HDL-C, HDL3-C, and apolipoprotein B (apo B) occurred in both groups, but only the
      LFMR group showed a trend toward beneficial changes in LDL-C/HDL-C and apo A-Vapo
      B ratios. Overall, the LFMR diet was well tolerated and resulted in an improved
      serum lipid and apolipoprotein profile.

PMID- 9252957
TI  - Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte
      membranes and platelets during dietary supplementation with fish, fish oil, and
      docosahexaenoic acid-rich oil among healthy young men.
AB  - The effects of n-3 fatty acid supplementation in the form of fresh fish, fish
      oil, and docosahexaenoic acid (DHA) oil on the fatty acid composition of plasma
      lipid fractions, and platelets and erythrocyte membranes of young healthy male
      students were examined. Altogether 59 subjects (aged 19-32 yr, body mass index
      16.8-31.3 kg/m2) were randomized into the following diet groups: (i) control
      group; (ii) fish diet group eating fish meals five times per week [0.38 +/- 0.04
      g elcosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA per day]; (iii) DHA oil
      group taking algae-derived DHA oil capsules (1.68 g/d DHA in triglyceride form);
      and (iv) fish oil group (1.33 g EPA and 0.95 g DHA/d as free fatty acids) for 14
      wk. The fatty acid composition of plasma lipids, platelets, and erythrocyte
      membranes was analyzed by gas chromatography. The subjects kept 4-d food records
      four times during the study to estimate the intake of nutrients. In the fish
      diet, in DHA oil, and in fish oil groups, the amounts of n-3 fatty acids
      increased and those of n-6 fatty acids decreased significantly in plasma lipid
      fractions and in platelets and erythrocyte membranes. A positive relationship was
      shown between the total n-3 polyunsaturated fatty acids (PUFA) and EPA and DHA
      intake and the increase in total n-3 PUFA and EPA and DHA in all lipid fractions
      analyzed. DHA was preferentially incorporated into phospholipid (PL) and
      triglyceride (TG) and there was very little uptake in cholesterol ester (CE),
      while EPA was preferentially incorporated into PL. and CE. The proportion of EPA
      in plasma lipids and platelets and erythrocyte membranes increased also by DHA
      supplementation, and the proportion of linoleic acid increased in platelets and
      erythrocyte membranes in the DHA oil group as well. These results suggest
      retroconversion of DHA to EPA and that DHA also interferes with linoleic acid
      metabolism.

PMID- 9252958
TI  - Heneicosapentaenoate (21:5n-3): its incorporation into lipids and its effects on
      arachidonic acid and eicosanoid synthesis.
AB  - 6,9,12,15,18-Heneicosapentaenoic acid (21:5n-3) (HPA), present in small amounts
      in fish oils, has been prepared by chemical elongation of eicosapentaenoic acid
      (EPA) and its biological properties compared with EPA and docosahexaenoic acid
      (DHA). All the double bonds of HPA are displaced one carbon away from the
      carboxyl group when compared to EPA. HPA is incorporated into phospholipids and
      into triacylglycerol in cell culture to a similar extent as EPA and DHA. HPA is a
      stronger inhibitor of the conversion of alpha-linoleic acid and dihomo-gamma
      linolenic acid to arachidonic acid (AA) in hepatoma cells than are EPA, DHA, and
      AA. HPA is a poor substrate for prostaglandin H synthase and for 5-lipoxygenase,
      but it inactivates prostaglandin H synthase as rapidly as do AA, EPA, and DHA.
      HPA inhibits thromboxane synthesis in isolated platelets as efficiently as EPA.
      EPA, HPA, and DHA are all weak inducers of acyl-CoA oxidase in hepatoma cells.
      Therefore, since fish oils contain only small amounts of HPA, it is unlikely that
      this fatty acid is of particular significance for the biological effects of these
      oils, possibly with the exception that it is a strong inhibitor of AA synthesis.

PMID- 9252959
TI  - Characterization of an HL-60 cell variant resistant to the antineoplastic ether
      lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine.
AB  - A resistant cell line (HL-60R) was selected by incubating HL-60 cells with
      increasing concentrations of 1-O-octadecyl-2-O-methyl-rac-glycero-3
      phosphocholine (ET-18-OCH3) and used to examine the mechanism of resistance to
      the antineoplastic ether-linked lipid. The HL-60R cells exhibited a > 10-fold
      increase in resistance when measured by [3H]-thymidine incorporation in
      comparison to the HL-60 cell line. ET-18-OCH3 binding occurred at 4 degrees C and
      was not saturable at the concentrations tested (1-100 microM), indicating that
      the binding was receptor-independent. At 4 degrees C, association of ET-18-OCH3
      was low for each cell line. AT 37 degrees C, uptake in the HL-60 cells was
      approximately 5-fold greater in comparison to HL-60R cells at each concentration
      tested. However, when the cellular content of ET-18-OCH3 was equal, both cell
      lines experienced similar declines in cell growth. Cellular incorporation of
      ether lipid was determined using serum-free media and in the presence of serum
      albumin or lipoproteins. Reduced uptake by the resistant cell line was observed
      only in the presence of albumin. A greater proportion of ether lipid could be
      removed from prelabeled HL-60R cells than from HL-60 cells, by an albumin wash
      procedure, indicating an increased rate of internalization and retention by the
      sensitive cell line. ET-18-OCH3 uptake in the HL-60 cell line was also more
      sensitive to treatment with endocytic (chloroquine, monensin) or metabolic (NaF,
      KCN) inhibitors. These results suggest that uptake is the principal determinant
      influencing sensitivity of the resistant cell line and consists of receptor
      independent binding followed by internalization. Differential uptake requires the
      presence of serum albumin and is dependent on the energy-dependent endocytosis of
      the ether lipid.

PMID- 9252960
TI  - Conjugated linoleic acid modulation of phorbol ester-induced events in murine
      keratinocytes.
AB  - Recent work in our lab has shown that the chemoprotective fatty acid, conjugated
      linoleic acid (CLA), inhibits phorbol ester skin tumor promotion in mice. Because
      little is known about the deposition of CLA into tissues as well as its
      biological activity, this study compared the incorporation and biological
      activity of CLA to linoleic acid (LA; 18:2, c9,c12) and arachidonic acid (AA;
      20:4 c5,c8,c11,c14) in cultured keratinocytes. When keratinocytes (HEL-30) were
      grown in media containing 14C-CLA for various periods, more than 50% of the 14C
      CLA was incorporated into cellular lipids by 9 h. The distribution of CLA in
      phospholipid classes was similar to LA, Approximately 50% of 14C-LA and 14C-CLA
      were incorporated into phosphatidylcholine (PC), while the remainder was taken up
      by phosphatidylethanolamine (PE) and phosphatidylserine/phosphatidylinositol
      (PS/PI). In contrast, 14C-AA was more equitably distributed into PC, PE, or PS/PI
      (27, 30, or 38%, respectively). When keratinocytes were prelabeled with
      radiolabeled fatty acids, phorbol ester-induced release of 14C-CLA was 1.5 times
      higher than 14C-LA and 14C-AA. However, 14C-prostaglandin E (PGE) release in 14C
      CLA prelabeled cultures was 6 and 13 times lower than cultures treated with 14C
      LA and 14C-AA, respectively. Moreover, the ability of non-radiolabeled CLA to
      support ornithine decarboxylase activity, a hallmark event of tumor promotion,
      was significantly lower than in LA- and AA-treated cultures. These studies
      suggest that CLA inhibits skin tumor promotion, in part, through a PGE-dependent
      mechanism.

PMID- 9252961
TI  - Conversion of 18:3 delta 9cis, 12cis, 15trans in rat liver microsomes.
AB  - Several years ago, it was established that the delta 15 trans isomer of alpha
      linolenic acid is converted in vivo into fatty acids containing 20 and 22 carbons
      (geometrical isomers of eicosapentaenoic and docosahexaenoic acids). The present
      study focused on the in vitro delta 6 desaturation, the first step of the
      biosynthesis of the n-3 long-chain polyunsaturated fatty acids from 18:3n-3. For
      that purpose, rat liver microsomes were prepared and incubated with radiolabeled
      18:3 delta 9cis,12cis,15cis (18:3c,c,c) or 18:3 delta 9cis, 12cis, 15trans
      (18:3c,c,t) under desaturation conditions. The data show that 18:3c,c,t is
      converted at a lower rate compared with alpha-linolenic acid. The product of
      conversion of 18:3c,c,t may be 18:4 delta 6cis, 9cis, 12cis, 15trans resulting
      from a delta 6 desaturation of the trans substrate. Moreover, the conversion of
      radiolabeled 18:3c,c,t was strongly decreased by the presence of 18:3c,c,c (up to
      48%) while the 18:3c,c,t only slightly decreased the conversion of radiolabeled
      18:3c,c,c. Thus, the desaturation enzyme presented a higher affinity for the
      native all-cis n-3 substrate.

PMID- 9252963
TI  - Unusual effects of some vegetable oils on the survival time of stroke-prone
      spontaneously hypertensive rats.
AB  - Preliminary experiments have shown that a diet containing 10% rapeseed oil (low
      erucic acid) markedly shortens the survival time of stroke-prone spontaneously
      hypertensive (SHRSP) rats under 1% NaCl loading as compared with diets containing
      perilla oil or soybean oil. High-oleate safflower oil and high-oleate sunflower
      oil were found to have survival time-shortening activities comparable to that of
      rapeseed oil; olive oil had slightly less activity. A mixture was made of soybean
      oil, perilla oil, and triolein partially purified from high-oleate sunflower oil
      to adjust the fatty acid composition to that of rapeseed oil. The survival time
      of this triolein/mixed oil group was between those of the rapeseed oil and
      soybean oil groups. When 1% NaCl was replaced with tap water, the survival time
      was prolonged by approximately 80%. Under these conditions, the rapeseed oil and
      evening primrose oil shortened the survival time by approximately 40% as compared
      with n-3 fatty acid-rich perilla and fish oil; lard, soybean oil, and safflower
      oil with relatively high n-6/n-3 ratios shortened the survival time by roughly
      10%. The observed unusual survival time-shortening activities of some vegetable
      oils (rapeseed, high-oleate safflower, high-oleate sunflower, olive, and evening
      primrose oil) may not be due to their unique fatty acid compositions, but these
      results suggest that these vegetable oils contain factor(s) which are detrimental
      to SHRSP rats.

PMID- 9252964
TI  - Oral acetylsalicylic acid induces biliary cholesterol secretion in the rat.
AB  - Several agents can alter biliary cholesterol secretion, critical for cholesterol
      excretion and gallstone formation. Although salicylate effects on bile formation
      and gallstones have been studied, biliary lipid secretion has not been measured
      during oral aspirin treatment. We examined whether oral acetylsalicylic acid
      affects bile lipid secretion. Three groups of young rats were fed chow for 3 wk.
      Two of the groups then received aspirin at either 1.67 or 3.33 g/kg diet for 4 d.
      Serum, hepatic, and bile lipids were measured, as were enzymes of cholesterol
      synthesis and esterification. With oral aspirin, bile cholesterol secretion
      increased by 42% and hepatic cholesteryl ester content decreased by 40%. Serum
      cholesterol and hepatic free cholesterol did not change. To evaluate mechanisms
      of the cholesterol hypersecretion, hypothyroid animals fed low-fat or fish oil
      diets and repleted with triiodothyronine were also studied. Aspirin stimulated
      cholesterol secretion to a degree similar to triiodothyronine. An additive
      response was seen in fish oil-fed rats. Aspirin did not appear to have a primary
      action on 3-hydroxy-3-methylglutaryl-CoA reductase or acyl CoA:cholesterol
      acyltransferase activities, and had no direct effect on esterification of
      cholesterol by isolated hepatocytes. Aspirin may directly increase cholesterol
      transport into bile or have cell membrane effects which alter cholesterol
      transport. It remains to be determined whether the observed alterations in bile
      cholesterol secretion are specific to the rat or also apply to humans.

PMID- 9252962
TI  - Increased hepatic beta-oxidation of docosahexaenoic acid, elongation of
      eicosapentaenoic acid, and acylation of lysophosphatidate in rats fed a
      docosahexaenoic acid-enriched diet.
AB  - Rats were fed a diet supplemented with corn oil (n-3 deficient), soy oil, or a
      mixture containing 8% 22:6n-3 ethyl ester for 6 wk. The hepatic capacities for
      the beta-oxidation and synthesis of 22:6n-3, in addition to the acylation of
      lysophosphatidate, were tested in vitro. In rats that were fed a 22:6n-3-enriched
      diet, both the beta-oxidation of 22:6n-3 and elongation of 20:5n-3 were enhanced
      compared to those in rats fed the other diets. Acylation of lysophosphatidate was
      also enhanced in rats fed a 22:6n-3-enriched diet, while the rate of
      dephosphorylation of phosphatidate was not changed. The amount of 22:6n-3 in the
      liver was much less than that consumed in a docosahexaenoic acid-enriched diet.
      These results suggest that a significant amount of dietary 22:6n-3 was degraded
      via beta-oxidation, and that a portion of the retroconverted 20:5n-3 was recycled
      for the synthesis of 22:6n-3. The recycling of 20:5n-3 might contribute to the
      low level of 22:6n-3 in rats fed an n-3-deficient diet.

PMID- 9252965
TI  - gamma-Linolenic acid-containing diet attenuates bleomycin-induced lung fibrosis
      in hamsters.
AB  - Although bleomycin (BLM), an antineoplastic drug, is used in the treatment of a
      variety of tumors, the mechanism(s) that contribute to its induced lung injury
      and fibrosis are not fully elucidated. Since alterations in the levels of certain
      fatty acid metabolites have been associated with BLM-induced lung injury, we
      tested the effects of dietary gamma-linolenic acid (GLA)-containing evening
      primrose oil on BLM-induced morphological alterations in the hamster lung, the
      marked elevation of tissue hydroxyproline (a marker for collagen synthesis), and
      elevated generation of arachidonic acid metabolites (marker of inflammatory
      mediators). Our data revealed that after 14 d of dietary GLA-containing oil (i)
      BLM-induced elevation of lung hydroxyproline was suppressed (P < 0.05), (ii) the
      marked BLM-induced elevation of lung leukotriene B4 (LTB4) (a marker of
      polymorphanuclear generation of proinflammatory LTB4) was significantly
      suppressed (P < 0.05). The decrease in LTB4 was accompanied by marked elevations
      (P < 0.05) of lung prostaglandin E1 (PGE1) and 15-hydroxyeicosatrienoic acid (15
      HETrE), both with known antiinflammatory properties. Taken together, data from
      these studies suggest that dietary GLA-containing oil contributes to tissue
      elevation of PGE1 and 15-HETrE, which in vivo may attenuate lung inflammation and
      fibrosis.

PMID- 9252966
TI  - Oleanolic acid and ursolic acid stabilize liposomal membranes.
AB  - The effects of oleanolic acid (OA) and ursolic acid (UA) on the fluidity and
      stability of dipalmitoyl phosphatidylcholine (DPPC) liposomal membrane were
      monitored by measuring the fluorescence polarization of 1,6-diphenyl-1,3,5
      hexatriene labeled in the liposomal membrane and the leakage of calcein from the
      probe-encapsulated liposomes. The experiments with the liposomes made of DPPC and
      OA or UA showed that OA and UA exhibited a moderate fluidity-modulating effect
      for the liquid-crystalline liposomal membrane, and a strong condensing effect for
      both crystalline and liquid-crystalline liposomal membranes. Their effects were
      comparable to those of cholesterol. These results suggest that their fluidity
      modulating and condensing effects might have some implications in their
      biological functions.

PMID- 9252967
TI  - An improved synthesis of taurine- and glycine-conjugated bile acids.
AB  - A simple and efficient method for the synthesis of taurine- and glycine
      conjugated bile acids is described. The condensation reaction was achieved by the
      simple mixing of unconjugated bile acid (1.0 eq.), taurine (2.0 eq.) (or
      glycinate ester), diethyl phosphorocyanidate (1.2 eq.) in the presence of
      triethylamine at room temperature for 30-60 min. Sample clean-up was effected by
      the use of a prepacked Sep-Pak C18 cartridge for reversed-phase solid extraction
      or by direct recrystallization, yielding the desired taurine and glycine
      conjugates in 89-93 and 92-96% isolated yields, respectively.

PMID- 9252968
TI  - A synthesis of 4-hydroxy-2-trans-nonenal and 4-(3H) 4-hydroxy-2-trans-nonenal.
AB  - 4-Hydroxy-2-trans-nonenal, the most abundant and toxic unsaturated aldehyde
      generated during membrane lipid peroxidation, was synthesized starting from
      fumaraldehyde dimethyl acetal. In the first step of the synthesis, the
      fumaraldehyde dimethyl acetal was partially hydrolyzed using amberlyst catalyst
      to obtain the monoacetal. The 4-hydroxy-2-trans-nonenal was synthesized by the
      Grignard reaction of the fumaraldehyde monoacetal with 1-bromopentane. 4-Hydroxy
      2-trans-nonenal, obtained as its dimethylacetal, was oxidized to its
      corresponding 4-keto derivative using pyridinium chlorochromate buffered with
      sodium acetate as the oxidizing agent. 4-(3H) 4-Hydroxy-2-trans-nonenal was
      obtained in one step by the sodium borotriteride reduction of the 4-keto
      derivative.

PMID- 9252969
TI  - Chromogenic assay for phospholipase D from Streptomyces chromofuscus: application
      to the evaluation of substrate analogs.
AB  - A rapid and convenient chromogenic assay for phospholipase D from Streptomyces
      chromofuscus (PLDSc) has been developed that converts the choline generated from
      the enzyme-catalyzed hydrolysis of phospholipids into a chromogenic dye. By
      quenching the reaction with EDTA at defined times, an initial rate curve is
      produced from which a kcat and K(m) can be readily derived. This assay has been
      applied to the biological evaluation of several substrate analogs, all of which
      appear to be activators rather than substrates or inhibitors of this enzyme.
      Performing the assay in 96-well microtiter plates allows for the easy screening
      of potential effectors of this enzyme.

PMID- 9252970
TI  - Structural characterization of a "signature" phosphatidylethanolamine as the
      major 10-hydroxy stearic acid-containing lipid of Cryptosporidium parvum oocysts.
AB  - A 10-hydroxy stearic acid-containing lipid from Cryptosporidium parvum was
      purified by thin-layer chromatography and analyzed by infrared spectroscopy, fast
      atom bombardment mass spectrometry, 1H and 31P nuclear magnetic resonance
      spectroscopy, and was identified as phosphatidyl-ethanolamine.

PMID- 9252971
TI  - Osteopenia induced by long-term, low- and high-level exposure of the adult rat to
      lead.
AB  - The skeleton, the major site for Pb accumulation, is responsible for the largest
      fraction of the total body burden, but long-term effects of low-level exposure in
      adults remain unclear. In this study rats were exposed to low (0.01%; 100 ppm,
      LoPb) or high (0.5%, 5,000 ppm, HiPb) Pb, low calcium, feeding regimes for 1-12
      months. Both LoPb and HiPb animals showed significant 12-month blood Pb levels
      [LoPb 21 +/- 3 micrograms/dl; HiPb 59 +/- 18; controls 3 +/- 1 (mean +/- SEM), p
      = 0.001]. Dual energy X-ray densitometry of the femur detected a significant
      decrease in bone density in HiPb animals by 3 months which remained significantly
      lowered through 12 months [3 months: HiPb: 0.498 +/- 0.011 (6) vs. control: 0.546
      +/- 0.012 (6), p < 0.003]. By 12 months' density was also significantly lowered
      in LoPb animals (p = 0.001). Mineral analyses of ashed femurs showed a
      significant lead content after 1, 3, 9 and 12 months' exposure [1 month: LoPb,
      0.020 +/- 0.002 (4) (% ash weight) vs control 0.008 +/- 0.0004 (4); HiPb 0.016 +/
      0.001 (8); control 0.007 +/- 0.0004 (6) (p < or = 0.002)]. Ca levels (% ash
      weight) were significantly lowered at 9 months in HiPb and 12 months in both
      groups (p < or = 0.04). Quantitative histomorphometry documented significantly
      elevated osteoid and resorptive trabecular surface features in both Pb groups.
      The LoPb design produced no overt renal functional abnormalities and resulted in
      blood Pb values comparable to those in man with modest environmental Pb exposure.
      The HiPb design resulted in development of lead nephropathy (more severe from
      months 6-12) and produced blood lead levels comparable to those seen in past
      industrial exposure. Findings show that Pb is incorporated into bone mineral
      after only 1 month's exposure to LoPb with significant osteopenia after 12
      months' exposure; HiPb caused osteopenia by 3 months. No normal compensatory
      mechanism was elicited to maintain bone mass. Results stress renewed concern
      about the effects of cumulative, low-level lead exposure in our elderly
      population.

PMID- 9252972
TI  - Sodium distribution in black and white women.
AB  - Delayed gamma neutron activation analysis (DGNA) was performed on 99 black and
      168 healthy white women, aged 20-80 years, to examine sodium distribution in the
      two ethnic groups. Elements measured included total body levels of sodium (TBNa)
      and chlorine (TBCl). The black women were heavier, and consequently had a higher
      body surface area. Sodium excess (Naes) was calculated from TBNa and TBCl. Total
      body water was measured by tritiated water dilution. TBNa was higher in black
      than white women, and this difference persisted when the values were corrected
      for body surface area. TBNa and Naes declined significantly with age in white
      women, whereas extracellular fluid sodium (ECFNa) remained constant. The change
      with age was not statistically significant in black women for TBNa, Naes or
      ECFNa. Our sample of healthy black women had a higher TBNa and Naes than healthy
      white women. This difference persisted after adjustment for body surface area, so
      that values for sodium distribution need to be adjusted for race. The change in
      TBNa with age in white women appears to be due to their decline of skeletal
      tissue mass with a consequent decline in nonexchangeable sodium.

PMID- 9252973
TI  - Stimulation by citric acid of calcium and phosphorus bioavailability in rats fed
      a calcium-rich diet.
AB  - The effect of dietary citric acid supplementation on calcium (Ca) and phosphorus
      (P) bioavailability was studied in rats fed 3 different diets containing 0.1, 0.5
      or 1.0 g/100g Ca during 7 weeks. Citric acid supplementation increased intestinal
      Ca and P absorption and the Ca and P retention/intake ratio only in rats fed the
      1% Ca diet. It also increased the P concentration of bone ashes in rats fed the
      0.5% Ca diet (18.9 +/- 0.2 vs 17.5 +/- 0.5%) and the 1% Ca diet (20 +/- 0.1 vs.
      19 +/- 0.3%), and the Ca bone ash concentration in rats fed the 1% Ca diet (36.7
      +/- 0.4 vs. 35.7 +/- 0.5%). In rats fed the 1% Ca diet, plasma P concentration
      was decreased by citric acid supplementation (2.09 +/- 0.10 vs. 2.45 +/- 0.08
      mmol/l) while urinary P excretion was increased (18.2 +/- 2.3 vs. 2.0 +/- 0.3
      mmol/4 days), together with a decrease in plasma calcitriol concentration (54.4
      +/- 2.6 vs. 79.6 +/- 2.5 ng/l), but no change of the circulating parathyroid
      hormone level. This study indicates that citric acid supplementation together
      with a Ca-rich diet allows to obtain an increased retention of Ca and P in bone.
      The prolonged administration of Ca citrate supplements may therefore help to
      increase bone mineral concentration.

PMID- 9252974
TI  - Intestinal calcium absorption from mineral water.
AB  - Little is known about the bioavailability of calcium in water and various
      beverages. Some mineral waters contain large amounts of calcium that could
      compensate for insufficient consumption of dairy products. The fractional
      intestinal absorption of calcium (FCA) was measured in 12 healthy adult
      volunteers, using a trace dose of radiocalcium and 200 mg of calcium carrier,
      part of which was calcium contained in mineral water. Measurements were performed
      in fasting subjects consuming a standard breakfast. In all the subjects, three
      mineral waters with a calcium concentration of 10.4, 78, and 467 mg/l,
      respectively, were tested. Calcium absorption occurred with the same kinetics for
      each of the mineral waters tested, and within 2 h of the oral dose, equilibrium
      was reached between absorbed calcium and calcium remaining in the
      gastrointestinal tract, which resulted in a constant FCA value. This level
      comprising between 34.1 and 37.0% was independent of the daily calcium
      consumption and the chemical content of the mineral water. In conclusion, calcium
      contained in mineral waters in available for intestinal absorption. In a given
      normal subject, the only rate-limiting factor for FCA is the amount of total
      calcium given with foods and drinks. Mineral waters containing calcium are
      recommended as a supplemental source of calcium to achieve optimal calcium
      requirements, especially in aged people with lactose intolerance.

PMID- 9252975
TI  - Short-term effect of parathyroidectomy on biochemical markers in primary and
      secondary hyperparathyroidism.
AB  - This study has been carried out in order to evaluate several bone metabolic
      markers after parathyroidectomy in patients with primary hyperparathyroidism
      (PHP) and secondary hyperparathyroidism (SHP). The subjects studied were 6
      patients with PHP (5 females, 1 male, aged 64-83 years) and 5 patients with SHP
      on chronic maintenance hemodialysis with skeletal symptoms (2 females, 3 males,
      aged 57-67 years). In PHP, serum alkaline phosphatase (ALP) and procollagen type
      I carboxy-terminal propeptides (PICP) levels showed a trend to increase gradually
      after parathyroidectomy, changes which were statistically significant (ALP, p =
      0.0375; PICP, p = 0.0006). The serum bone Gla protein (BGP) level showed no
      significant change throughout the pre- and postoperative periods (p = 0.7512).
      Urinary pyridinoline (Pyr.) and deoxypyridinoline (DPyr.) levels showed rapid
      decreases after parathyroidectomy (Pyr.; p = 0.0014, DPyr., p = 0.0087). In SHP,
      individual values of serum ALP in 3 patients with complete parathyroid resection
      and 1 patient with incomplete parathyroid resection showed a tendency to
      increase. Individual values of serum BGP and PICP increased after
      parathyroidectomy in 3 patients with complete parathyroid resection but not in
      the 2 patients with incomplete parathyroid resection. Individual values of the
      serum carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen
      (ICTP) level showed no certain trend. The results obtained after surgery indicate
      that there is a positive uncoupling of the two processes of bone remodeling, and
      serum PICP and urinary pyridinium cross-links are good specific markers for the
      evaluation of potential recovery of bone damage after parathyroidectomy.

PMID- 9252976
TI  - Boron diffusion across the dialysis membrane during hemodialysis.
AB  - To investigate the movement of boron across the dialysis membrane, serum and
      dialysate boron levels of long-term hemodialysis (HD) patients (n = 17) were
      determined using inductively coupled plasma emission spectrometry in both the
      inlet and the outlet side of the dialyzer. Results revealed that 77.8% of the
      serum boron in the inlet side of the dialyzer was filterable and 94.4% of
      filterable boron was actually filtered during HD. Boron dialysance was found to
      be 138.6 +/- 16.1 ml/min, and this value was higher than the clearance value of
      blood urea nitrogen (not significant), phosphorus and creatinine (p < 0.001). It
      is concluded that HD is effective in eliminating serum boron even at low
      concentrations, and boron can be classified as an element that is easily
      diffusible across the dialysis membrane. There seems to be relatively little
      relation of boron to serum constituents of macromolecules that are reported to
      have a major impact on the diffusion of trace elements across the HD membrane.

PMID- 9252977
TI  - Hypomagnesemic hypokalemia and hypocalcemia: clinical and laboratory
      characteristics.
AB  - Clinically important electrolyte disturbances such as hypokalemia and
      hypocalcemia have been well described in patients with hypomagnesemia of various
      causes. We undertook the present study to describe in detail the clinical
      characteristics as well as the acid base and electrolyte abnormalities in an
      effort to better understand the conditions that favor the appearance of this
      syndrome of hypomagnesemic hypokalemia and hypocalcemia, and the underlying
      pathogenetic mechanisms. A total of 35 adult patients (23 male, 12 female), aged
      21-79 years, who exhibited profound hypomagnesemia, hypokalemia, and hypocalcemia
      on their admission were studied. The most common causes of the syndrome were
      alcoholism and cisplatin administration. All but 2 patients with diarrhea had
      inappropriate magnesiuria. Despite hypokalemia and hypocalcemia all patients
      exhibited renal potassium and calcium wasting. Eight alcoholic patients with
      alcohol withdrawal syndrome or acute intoxication had pure respiratory alkalosis,
      while 6 patients with severe hypokalemia presented with metabolic alkalosis.
      Three chronic alcoholic patients exhibited metabolic alkalosis coexisting with
      respiratory alkalosis, while 1 alcoholic patient had the syndrome of alcoholic
      ketoacidosis. Hyponatremia was evident in only 2 patients with clinical and
      laboratory evidence of extracellular volume depletion. Hypophosphatemia was
      observed in 12 patients mainly due to inappropriate phosphaturia. Finally,
      hyperphosphatemia was found in 2 alcoholic patients with severe respiratory
      alkalosis. In conclusion, patients with hypomagnesemic hypokalemia and
      hypocalcemia exhibit multiple interrelated acid base and electrolyte
      abnormalities and mainly hypokalemia due to inappropriate kaliuresis,
      hypophosphatemia or rarely hyperphosphatemia, respiratory and metabolic
      alkalosis, as well as mixed acid base disorders.

PMID- 9252978
TI  - Interaction between extracellular calcium and endothelin-1 influences parathyroid
      hormone secretion from bovine parathyroid cells through the increase in
      intracellular calcium.
AB  - Endothelin-1 (ET-1) secretion from bovine parathyroid cells (bPTCs) responds to
      the changes in extracellular calcium concentrations ([Ca2+]c) and ET-1 inhibits
      parathyroid hormone (PTH) secretion. However, the effect from the interaction
      between [Ca2+]e and ET-1 on PTH secretion is unknown. To clarify these issues, a
      bPTC suspension was used to study the regulation of ET-1 secretion by subtle
      changes in [Ca2+]e and PTH secretion by the interaction between [Ca2+]e and ET-1.
      We added [Ca2+]e at varying concentrations, 0.5-2.0 mM, to the bPTC medium to
      define the relationship between [Ca2+]e and ET-1 secretion and found that the ET
      1 secretion was inversely regulated by [Ca2+]e with a low [Ca2+]e stimulating,
      and a high [Ca2+]e inhibiting ET-1 secretion. It is even suppressed to an
      undetectable level at a [Ca2+]e of > 1.5 mM. Further, we worked to determine how
      the interaction between ET-1 and [Ca2+]e influences PTH secretion. ET-1 > or =
      10(-10) M, inhibited PTH secretion in a dose-dependent manner and significantly
      inhibited PTH secretion at a low or normal [Ca2+]e. At an ET-1 concentration of >
      or = 10(-10) M, the 'calcium-PTH' relation showed significant changes in
      physiological responses. The effect of ET-1 on intracellular calcium
      concentrations ([Ca2+]i) of bPTCs was studied using the fura 2 fluorescence
      method. We found that increasing doses of ET-1 induced a progressive increase in
      [Ca2+]i of bPTCs. Our results suggest that ET-1 secretion is inversely regulated
      by [Ca2+]e. ET-1 can inhibit PTH secretion and alter the parathyroid secretion
      pattern to various calcium stimuli. ET-1 also elevates [Ca2+]i and this may be a
      part of the intracellular signaling mechanisms involved in the inhibition of PTH
      secretion from bPTCs.

PMID- 9252979
TI  - Extracellular magnesium depletion in pediatric patients with insulin-dependent
      diabetes mellitus.
AB  - It is unclear whether insulin-dependent diabetes mellitus is a state of magnesium
      depletion. This is a relevant question, since magnesium deficiency has been
      implicated in the pathogenesis of diseases that develop to an increased extent
      into diabetes mellitus. Total plasma magnesium was not statistically different in
      76 pediatric patients with insulin-dependent diabetes mellitus (0.77 [0.73-0.81]
      mmol/l; median and interquartile range), 59 healthy adults (0.80 [0.77-0.83]
      mmol/l) and 19 healthy children (0.80 [0.78-0.83] mmol/l). In contrast, plasma
      ionized magnesium, the most interesting form with respect to physiological and
      biological properties, was significantly lower in diabetic patients (0.50 [0.48
      0.53] mmol/l) when compared with healthy adults (0.53 [0.50-0.56] mmol/l; p <
      0.01) and healthy children (0.54 [0.51-0.56] mmol/l; p < 0.02). Our report
      confirms recent findings of reduced circulating ionized magnesium but normal
      circulating total magnesium in adults with non-insulin-dependent diabetes
      mellitus.

PMID- 9252980
TI  - Isolation of IL-2 receptor-beta cDNA clones from AtT-20 pituitary cells:
      constitutive expression and role in signal transduction.
AB  - Interleukin-2 (IL-2) has been shown to stimulate ACTH secretion by anterior
      pituitary cells and has been implicated in pathophysiological processes of the
      pituitary and brain in several major neuropsychiatric disorders. The present
      study tested the hypothesis that IL-2 receptor-beta (IL-2R beta), a
      constitutively expressed and essential subunit for IL-2 signaling in lymphocytes,
      is expressed by AtT-20 pituitary cells and involved in transducing intracellular
      signals induced by IL-2. We isolated and sequenced three overlapping IL-2R beta
      cDNA clones from AtT-20 pituitary cells representing key regions of the gene
      protein coding sequence. These cDNA clones including conserved sequences shared
      by growth hormone and prolactin as well as intracytoplasmic Src and JAK family
      homology domains of nonreceptor protein tyrosine kinases essential for IL-2
      signaling in lymphocytes. Their nucleotide sequences were 100% homologous with
      those expressed by lymphocytes (together they comprised 70% of the full length
      coding sequence). The IL-2R beta gene is constitutively expressed by AtT-20
      pituitary cells, and its transcription was upregulated after CRF stimulation.
      Species-specific Il-2 induced intracellular signals in AtT-20 cells known to be
      mediated by Il-2R beta, including a transient increase in c-myc nuclear proto
      oncogene transcription and the dose-dependent induction of DNA replication as
      measured by [3H]thymidine incorporation. The IL-2-induced DNA replication signal
      was not delivered by heat inactivated IL-2 and was partially blocked by a murine
      anti-IL-2R beta monoclonal antibody. These studies suggest that IL-2R beta may be
      a critical target involved in mediating the neuroimmunological actions of this
      prototypical cytokine in endocrine cells.

PMID- 9252981
TI  - In vivo occupancy of D2 dopamine receptors by nafadotride.
AB  - Nafadotride has been proposed as a selective antagonist for the D3 dopamine
      receptor. This drug has been shown to exhibit selectivity between D2 and D3
      dopamine receptors in in vitro assay systems; however, the in vivo D2/D3
      selectivity of the compound has not been determined. In this study, protection
      against inactivation by EEDQ was used as a measure of in vivo occupancy of D2
      receptors by behaviorally relevant doses of nafadotride (0.1-10 mg/kg, s.c. and
      i.p.) in adult, male Sprague-Dawley rats. Ex vivo [3H]spiperone binding was then
      determined in striatal membranes, l-Nafadotride (10 mg/kg) protected 71% of D2
      receptors after s.c. administration; 40% after i.p. administration. Protection of
      13% of D2 receptors was observed at a dose of 3 mg/kg (s.c.). These data suggest
      that blockade of D2 receptors contributes to the pharmacological effects of
      nafadotride when administered at doses above 1 mg/kg (s.c.) or 3 mg/kg (i.p.).

PMID- 9252982
TI  - Effects of sleep deprivation on serotonergic neuronal activity in the dorsal
      raphe nucleus of the freely moving cat.
AB  - Total sleep deprivation (TSD) for one or more nights produces a rapid
      antidepressant response in humans. Since most pharmacological treatments for
      depression increase brain serotonin neurotransmission, the purpose of the present
      study was to determine whether TSD increases the activity of serotonergic neurons
      in the dorsal raphe nucleus (DRN) in cats. Cats were prevented from sleeping by
      the experimenter, who monitored the behavioral state of each animal on a
      polygraph. Firing rates during quiet waking (QW) and active waking (AW) were
      obtained throughout a 24-h sleep deprivation period and subsequent 6-h recovery
      period. During the experiments, unit activity was also recorded during exposure
      to loud white noise, which elicited strong behavioral arousal. The inhibitory
      response of serotonergic DRN neurons to systemic administration of the selective
      5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was determined
      before and after TSD to assess possible changes in 5-HT1A autoreceptor
      sensitivity. TSD increased mean firing rates by as much as 18% during both AW and
      white noise exposure. Maximal effects were observed after 15 h of TSD for AW, and
      after 18 h for white noise. QW firing rates also tended to be elevated throughout
      TSD. Firing rates for all conditions during the recovery period were not
      significantly different from baseline. The neuronal inhibition produced by 8-OH
      DPAT was significantly diminished after TSD. Overall, these results indicate that
      TSD increases the firing rate of serotonergic DRN neurons during AW and arousal.
      This effect may be attributable to a decrease in the sensitivity of 5-HT1A
      autoreceptors. These findings are consistent with the hypothesis that TSD exerts
      its antidepressant action, at least in part, through an activation of brain
      serotonergic neurons.

PMID- 9252983
TI  - Adenosine A2A agonists: a potential new type of atypical antipsychotic.
AB  - The systemic intraperitoneal (i.p.) administration of the adenosine A2A agonist
      CGS 21680 was found to dose-dependently antagonize spontaneous and amphetamine
      induced (1 mg/kg i.p.) motor activity with similar ED50 values (about 0.2 mg/kg).
      The ratios between the ED50 values for induction of catalepsy and for
      antagonizing amphetamine-induced motor activity for CGS 21680, haloperidol, and
      clozapine were 12, 2, and > 30, respectively. Furthermore, CGS 21680 was
      comparably much stronger than haloperidol or clozapine at antagonizing the motor
      activity induced by phencyclidine (2 mg/kg subcutaneously) than motor activity
      induced by amphetamine (1 mg/kg i.p.). In conclusion, the present results show a
      clear "atypical" antipsychotic profile of the adenosine A2A agonist CGS 21680 in
      animal models.

PMID- 9252984
TI  - Subchronic phencyclidine administration reduces mesoprefrontal dopamine
      utilization and impairs prefrontal cortical-dependent cognition in the rat.
AB  - Repeated ingestion of phencyclidine by humans induces enduring schizophrenic
      symptomatology, particularly cognitive dysfunction. In the presently described
      series of experiments, the neurochemical and cognitive consequences of subchronic
      phencyclidine administration in the rat were explored. Repeated phencyclidine
      exposure led to a selective reduction in basal and stress-evoked dopamine
      utilization in the prefrontal cortex. In addition, rats previously subchronically
      treated with phencyclidine were impaired on performance of a spatial working
      memory task in a delay-dependent manner. Importantly, these dopaminergic and
      cognitive deficits were observed after withdrawal from phencyclidine, and as
      such, the neurochemical and behavioral effects were due to drug-induced
      neurobiological changes rather than direct drug effects. These biochemical and
      behavioral data show that repeated phencyclidine administration induces
      prefrontal cortical cognitive deficits in rats, as in humans, and offer a
      biochemical perspective of the neural substrate underlying this cognitive
      impairment: inhibition of mesocortical dopamine neurons. Thus, these data may
      have relevance to psychiatric disorders involving prefrontal cortical
      dopaminergic hypoactivity and cognitive dysfunction, as has been hypothesized in
      schizophrenia.

PMID- 9252985
TI  - Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid
      receptor mRNA expression in the luteal phase of the menstrual cycle.
AB  - We examined the effects of the menstrual cycle on hypothalamic-pituitary adrenal
      axis regulation in healthy women with no history of psychiatric illness by
      measuring plasma cortisol responses to a low-dose (0.25 mg) of dexamethasone (N =
      23) and by measuring glucocorticoid receptor (type II) mRNA expression in
      lymphocytes using Northern blotting (N = 19). Both measures were performed in the
      early follicular and mid-luteal phases of the menstrual cycle. Dexamethasone
      suppression of plasma cortisol was greater in the follicular phase of the
      menstrual cycle compared to the mid-luteal phase (p < .01). In addition, type II
      glucocorticoid receptor mRNA expression in lymphocytes was 78% higher in the
      follicular phase compared to the mid-luteal phase (p < .02). These results
      indicate that glucocorticoid feedback regulation of the hypothalamic-pituitary
      adrenal axis is reduced in the mid-luteal phase of the menstrual cycle. Reduced
      feedback regulation of central stress response systems may play a role in
      generation of common premenstrual symptoms of irritability and dysphoria.

PMID- 9252986
TI  - Can the effects of antidepressants be observed in the first two weeks of
      treatment?

PMID- 9252987
TI  - The problem of gestalt in neurobiology.
AB  - The question of gestalts is discussed within the framework of its neuronal
      mechanisms. Two basic hypotheses are considered: 1) that of gestalts as a result
      of the hierarchical organization of neurons (gnostic units), and 2) that of
      gestalts as a result of the synchronization of neurons of a given level. Analysis
      of published data led to the conclusion that gestalts result from vector coding
      in the hierarchical organization of neurons. High-frequency oscillations in the
      gamma range (40-200 Hz) are of endogenous origin, and their function is to
      reinforce the synaptic inputs to those neurons which are involved in the
      synthesis of a gestalt.

PMID- 9252988
TI  - Real-time distribution of linked spike activity in cortical neurons during
      learning in the cat.
AB  - Analysis of the distribution of linked spike activity showed changes occurring
      within the structure of interneuron functional connections during learning. In an
      electric shock defensive reflex, concentration of linked spikes from cat motor
      cortex neurons was observed on signal presentation, while in a conditioned food
      procuring reflex to time, this was confined to the moment at which reinforcement
      was provided. This can be regarded as the appearance of a reflex at the level of
      interneuron interactions. This conclusion is supported by the observation that in
      well-trained animals, concentrations of linked spikes could be seen at the place
      of the conditioned reflex response, even in the absence of defensive and food
      procuring movements.

PMID- 9252989
TI  - Studies of the role of the brain cholinergic system in the mechanisms of
      dissociative learning.
AB  - Rats were trained to make conditioned food reflex excursions in two states: in
      normal conditions and on a background of treatment with pharmacological agents
      producing dissociative states. A number of cholinergic substances were completely
      interchangeable in dissociative learning; anticholinergic compounds efficiently
      neutralized the ability of cholinergic substances to produce dissociative states;
      muscarinic cholinoreceptors played the leading role in production of the
      dissociative state.

PMID- 9252990
TI  - Direct activating effect of the lateral preoptic region of the hypothalamus on
      the synchronizing system of the thalamus.
AB  - Chronic studies on cats were used to analyze rearrangements of total
      bioelectrical activity and neuron responses in the median center of the thalamus
      to electrical stimulation of the lateral preoptic nucleus of the hypothalamus.
      These electrophysiological studies established the existence of ipsi- and
      contralateral projections from the preoptic region to the median center. The
      preoptic region was shown to have an activating effect on the thalamic mechanisms
      generating spindle activity. It is suggested that the preoptic region with the
      nonspecific thalamus, acting via direct hypothalamo-thalamic connections, is one
      of the mechanisms involving the preoptic somnogenic system in the initiation of
      sleep and in the formation of the slow-wave phase of sleep.

PMID- 9252991
TI  - Effects of changes in dynamic equilibrium in microtubule and microfilament
      systems on the plastic responses of neurons.
AB  - Studies were carried out on the effects of disruption and stabilization of
      microtubules and microfilaments on the formation of neuronal plastic responses in
      isolated nerve cells of the mollusk Lymnaea stagnalis. Disruption of these
      cytoskeletal elements prevented the development of neuronal plastic responses.
      Microtubule stabilization produced a dynamic relationship between the development
      and retention of neuronal plastic responses and series of stimuli. Stabilization
      of microfilaments blocked the development but promoted the retention of these
      neuronal responses.

PMID- 9252992
TI  - Time organization of frontal-motor cortex interneuron interactions in the cat
      neocortex in conditions of different levels of food motivation.
AB  - Studies were carried out in conscious cats with recording of multicellular
      activity in moderate hunger and after 24-h food deprivation. Cross-correlation
      analysis was used to assess statistical interneuron interactions between closely
      located neurons in the frontal and sensorimotor regions of the neocortex (local
      networks), and between the cells of these regions (distributed networks). One-day
      food deprivation increased the number of interactions formed within both local
      and distributed neuron networks. Increases in intercortical connections between
      the frontal and motor regions was seen at all time intervals studied (0-100
      msec), though the most significant changes occurred at time intervals of up to 30
      msec.

PMID- 9252993
TI  - Changes in the electrical characteristics of command neurons on development of a
      conditioned defensive reflex in the edible snail.

PMID- 9252994
TI  - A systems process of reinforcement.
AB  - Functional systems theory was used to consider the process of reinforcement of
      the actions on the body of reinforcing factors, i.e., the results of behavior
      satisfying the body's original needs. The systems process of reinforcement
      includes reverse afferentation entering the CNS from receptors acted upon by
      various parameters of the desired results, and mechanisms for comparing reverse
      afferentation with the apparatus which accepts the results of the action and the
      corresponding emotional component. A tight interaction between reinforcement and
      the dominant motivation is generated on the basis of the hologram principle.
      Reinforcement forms an apparatus for predicting a desired result, i.e. a result
      of-action acceptor. Reinforcement procedures significant changes in the
      activities of individual neurons in the various brain structures involved in
      dominant motivation, transforming their spike activity for a burst pattern to
      regular discharges; there are also molecular changes in neuron properties. After
      preliminary reinforcement, the corresponding motivation induces the ribosomal
      system of neurons to start synthesizing special effector molecules, which
      organize molecular engrams of the acceptor of the action's result. Sensory
      mechanisms of reinforcement are considered, with particular reference to the
      information role of emotions.

PMID- 9252995
TI  - Dynamics of high-frequency (up to 200 Hz) components of brain electrical activity
      during learning reflect the functional mosaicism of the neocortex.
AB  - This study was undertaken with the aim of identifying frequency bands with
      correlated changes in the spectral power amplitudes of brain electrical activity,
      including high-frequency components (the 1-200 Hz band) in four dogs, using one
      dimensional analysis. Factor and cluster analysis of the spectral densities of
      various parts of the cortex and the olfactory bulb were carried out. The ratios
      of factors in different parts of the brain, both in terms of the proportions of
      the total dispersity and in terms of weightings, provided data on regional and
      individual differences in electrical activity. During learning (development of a
      motor habit consisting of pressing a feeder pedal), the factor organization of
      electrical activity became more, complex, particularly in the high-frequency part
      of the spectrum (40-170 Hz). The changes consisted of the appearance of narrower
      frequency sub-bands, each of which was present at high weighting (0.7-0.9) for
      one of the factors. The use of high-frequency components allowed functional
      mosaicism of the neocortex to be detected.

PMID- 9252996
TI  - NMDA receptors and associative-type ultrastructural synaptic plasticity in the
      rat neocortex.

PMID- 9252997
TI  - Comparative neurobiology of color vision in humans and animals.
AB  - Discrimination of colors was studied using an instrumental learning paradigm in
      monkeys (Macaque rhesus) and fishes (Carpio cyprinus L.). The confusion matrices
      composed of probabilities of instrumental responses were treated by factor
      analysis. The spherical structure of perceptual color space revealed in both
      animals was similar to that in humans. The four eigenvectors constituting the
      four-dimensional Euclidean hypersphere correspond to "red-green," "blue-yellow,"
      "brightness," and "darkness" neuronal channels.

PMID- 9252998
TI  - Brain mechanisms of emotions.
AB  - At the 23rd International Congress of Physiology Sciences (Tokyo, 1965) the
      results of experiment led us to the conclusion that emotions were determined by
      the actual need and estimation of probability (possibility) of its satisfaction.
      Low probability of need satisfaction leads to negative emotions actively
      minimized by the subject. Increased probability of satisfaction, as compared to
      the earlier forecast, generates positive emotions which the subject tries to
      maximize, that is, to enhance, to prolong, to repeat. We named our concept the
      Need-Informational Theory of Emotions. According to this theory, motivation,
      emotion, and estimation of probability have different neuromorphological
      substrates. Activation through the hypothalamic motivatiogenic structures of the
      frontal parts of the neocortex orients the behavior to signals with a high
      probability of their reinforcement. At the same time the hippocampus is necessary
      for reactions to signals of low probability events, which are typical for the
      emotionally excited brain. By comparison of motivational excitation with
      available stimuli or their engrams, the amygdala selects a dominant motivation,
      destined to be satisfied in the first instance. In the cases of classical
      conditioning and escape reaction the reinforcement was related to involvement of
      the negative emotion's hypothalamic neurons, while in the course of avoidance
      reaction the positive emotion's neurons were involved. The role of the left and
      right frontal neocortex in the appearance or positive or negative emotions
      depends on these informational (cognitive) functions.

PMID- 9252999
TI  - Information synthesis in key parts of the cerebral cortex as the basis of
      subjective experience.
AB  - This paper discusses a number of principles of the organization of cerebral
      processes underlying subjective experiences. The concept developed here suggests
      that these experiences arise as a result of the synthesis of different types of
      information, this synthesis occurring in various parts of the cortex which have
      key roles in this mental function. The synthesis is made using information
      arriving from the external environment, information extracted from memory, and
      information arriving from motivational centers. The concept is based on studies
      of the cerebral mechanisms of perception and thought. Experiences are
      demonstrated to arise as a result of the synthesis, by neurons in the
      projectional cortex, of data describing the physical and informational properties
      of a stimulus; the mechanism of the synthesis is a circular movement of
      excitation from the projectional to the associative regions of the cortex, then
      to the hippocampus and motivational centers, with return of excitation to the
      projectional cortex. It is also demonstrated that the process of thought involves
      convergence of cortical connections on defined centers, which are called
      interaction foci. Different thought operations are associated with their own
      specific interaction focus topographies: in imaginative thinking, foci are
      located in the temporo-parietal cortex, while abstract thinking foci in the
      frontal cortex. It is suggested that information arriving by means of neural
      connections is compared and synthesized in interaction foci, and that this
      provides the basis for decision-making. The final part of this paper addresses
      the functional importance of mental phenomena and their possible effects on
      cerebral processes.

PMID- 9253000
TI  - Dynamic character and age dependence of functional brain organization in
      attention.
AB  - Intrahemispheric functional organization was studied during a task expectancy
      period with special reference to attention mechanisms. The estimation of
      coherence of functionally identical rhythmic EEG components was made to
      characterize the intracortical integration. Several factors influencing the
      possibility to make an adequate prognosis and to realize it were varied.
      Different types of the task (objective factor) were used. Subjects of different
      ages (7, 9-10 years, young adults) and children of the same age differing by the
      brain maturity level (subjective factor) were studied. It was shown that all
      factors studied have a certain influence on the brain organization underlying the
      task preceding attention. Clear age differences as well as the lag between the
      possibility to formation and realization of the prognosis in children were
      observed. Alternative "strategies" used in different ages to facilitate the task
      performance were analyzed; the underlying mechanisms were discussed.

PMID- 9253001
TI  - Reinforcement concept in investigations on simple nervous systems.
AB  - An analysis of the applicability of the concept of reinforcement to the studies
      of learning in simple nervous systems of invertebrates is made. Analysis of the
      literature data and my own results suggests that reinforcement cannot be regarded
      as an independent behavioral phenomenon. A description of reinforcement as a
      state of the nervous system which precedes long-term changes of behavior is
      given. Using the example of aversive conditioning to food in gastropod snails it
      is shown that a state of the network that can be correlated with the state of
      reinforcement can be elicited in the simple nervous system by activation of
      serotonergic pedal cells modulating avoidance behavior of the animal. The
      conclusion is made that with certain limitations the reinforcement concept can be
      used in studies on simple nervous systems.

PMID- 9253003
TI  - Sensory information--the major factor of ontogeny.
AB  - On the basis of their own data authors postulate that the increase in sensory
      input during early ontogeny results in a delay in the development of the sensory
      systems formed earlier. In connection with this, the sensory basis of behavioral
      patterns becomes ineffective, causing their reorganization and the appearance of
      new forms of behavior. Limitation of sensory input during during the critical
      periods of development stimulates the accelerated manifestation of behavioral
      patterns. However, this acceleration also has long-lasting negative effects -
      alterations in the process of learning and memory in adult animals.

PMID- 9253002
TI  - Formation and realization of individual experience.
AB  - This article describes the methodological approach of systemic psychophysiology.
      In the framework of this approach a wide range of experimental data is analyzed:
      results of neuronal recordings in vitro and in awake normal and pathological
      animals learning to perform and performing both complex instrumental and simple
      behavioral acts. Another block of analyzed data is based on experiments with
      human subjects who learn and perform the tasks of categorization of words and
      operator tasks, participate in group game activity, and answer the questionnaires
      of psychodiagnostic methods. As a result of this analysis, the systemic
      psychophysiology approach is used to describe qualitatively and quantitatively
      the formation and realization of individual experience.

PMID- 9253004
TI  - Biochemical correlates of individual behavior.
AB  - This article is a review of data (results of the authors' investigations and data
      from the literature) concerning neurochemical correlates of individual behavior
      in rats. The "emotional resonance" test was used for behavioral selection of
      rats. Individual behavior in this test is related to the differences in free
      radical-mediated processes, membrane lipid content, nitric oxide synthase
      activity, and cAMP pattern in cerebral macrostructures. Behavior-related
      differences may be revealed in intact animals; however, most of them are reactive
      (induced by significant external factors). These differences depend on age; they
      may be global, specific for selected brain regions, and/or related to
      interhemisphere lateralization of biochemical parameters.

PMID- 9253005
TI  - Is there a zone of vascular vulnerability in the fetal brain stem?
AB  - The pattern of malformations in congenital anomalies such as Mobius syndrome and
      following prenatal cocaine exposure suggests that there is a zone of vascular
      vulnerability or ischemic sensitivity in the paramedian region of the developing
      brain stem. In the present study, postmortem examination of the brain of an
      infant with Mobius syndrome revealed mineralized foci concentrated in paramedian
      wedge-shaped areas of the pontine and medullary tegmentum. We also examined the
      development of brain stem vasculature in the rat at the light and ultrastructural
      level to determine whether anatomical features of the paramedian brain stem
      region could contribute to elevated incidence of vascular accidents in that zone.
      Several observations of relevance to the question of vascular vulnerability of
      the midline were made. Firstly, and as previously noted by other authors, the
      brain stem midline remains avascular for protracted periods during fetal life. We
      propose that the inability of vessels in the paramedian region to anastomose
      across the avascular midline gives rise to paramedian watershed zones that could
      be vulnerable to ischaemia in the event of hypoperfusion due to teratogenic
      action. Secondly, we studied the development of cytochrome oxidase activity in
      the fetal brain stem and noted high oxidative metabolic activity of the somatic
      efferent nuclei in the paramedian region, which could render their constituent
      neurons particularly susceptible to hypoxia. Thirdly, our ultrastructural
      examination revealed large amounts of extracellular space surrounding paramedian
      pontine vessels in comparison to laterally placed vessels, although there was no
      significant difference between the vessels of the two regions in tight junction
      length and endothelial thickness. We propose that the greater proportion of
      unoccupied extracellular space surrounding medial vessels may contribute to
      poorer support of these vessels in ischemic/reperfusion episodes. This poor
      support could in turn give rise to an increased risk of hemorrhage.

PMID- 9253006
TI  - Neurobehavioral outcomes among farm and nonfarm rural Ecuadorians.
AB  - International researchers have urged greater use of simple neurobehavioral
      batteries in developing country settings where higher levels of exposure and a
      variety of cultural and demographic factors may both occur. We conducted a cross
      sectional survey of 144 farm members and 72 age and education frequency-matched
      controls from rural Ecuador, using an amplified Neurobehavioral Core Test
      Battery. Farm members ranged from those with only indirect pesticide contact to
      applicators regularly applying organophosphate and carbamate insecticides by
      backpack sprayer. The distributors of scores showed those with less than 4 years
      of formal education and at the extremes of age (< 16 or > 65 years old)
      contributed sufficiently to nonnormality that they had to be excluded from
      subsequent analyses (resultant n = 170). After adjustment for age and education,
      language-based IQ test scores and farm membership were the most consistent
      determinants of neurobehavioral outcomes. Visual-spatial tasks were the most
      sensitive to the effects of farm membership. Gender (women better than men),
      alcohol problems, and solvent use were also important for some neurobehavioral
      tests.

PMID- 9253007
TI  - Gender differences in the uptake of inorganic mercury by motor neurons.
AB  - Gender differences have been noted in the tissue distribution of mercury. We
      sought to determine if the uptake of low-dose inorganic mercury into motor
      neurons differs between male and female mice. Four male and four female mice were
      injected i.p. with 0.5 mg HgCl2/kg. In 50-microns sections of lumbar spinal cord
      stained with autometallography, six motor neuron cell bodies were selected for
      study. The volume percentage of mercury granules in the cell bodies was estimated
      using a confocal microscope. Mercury granules occupied more perikaryal volume in
      motor neurons from female mice (mean 3.7%) than from male mice (mean 2.2%) (p <
      or = 0.05). After the same dose, the amount of renal mercury measured by mass
      spectrometry was significantly less in six female than five male mice. In
      conclusion, female mice take up more inorganic mercury into their motor neurons
      than do male mice. This may be related to a smaller deposition of mercury in the
      female kidney, leaving more circulating mercury available to be taken up by motor
      axons.

PMID- 9253008
TI  - Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in
      the weanling rat.
AB  - On gestational day 7 pregnant rats were implanted with osmotic minipumps
      containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile
      water. Their offspring were cross-fostered so that they were exposed to methadone
      prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine
      (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone
      exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a
      brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of
      males exposed to methadone postnatally. No effects of perinatal methadone
      exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4
      hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly
      in males exposed to methadone prenatally. Striatal and parietal cortical 5
      hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased
      slightly in rats exposed to methadone postnatally. Although parietal cortical 5
      HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone
      exposure, the ratios of metabolite and precursor to 5-HT were not affected.
      Effects of methadone exposure appeared to depend upon the developmental stage at
      which exposure occurred and did not appear to result from the phenomenon of
      neonatal withdrawal. Changes in activity of these three neurotransmitter systems
      may contribute to the effect of perinatal methadone on the activity of other
      neurons, such as cholinergic neurons.

PMID- 9253010
TI  - Developmental neurotoxicity evaluation of the avermectin pesticide, emamectin
      benzoate, in Sprague-Dawley rats.
AB  - The potential of emamectin benzoate (EB) to cause developmental neurotoxicity in
      Sprague-Dawley rats was assessed using a study design by the US EPA. Dosages of 0
      (deionized water), 0.1, 0.6, or 3.6 mg/kg/day were administered at 5 ml/kg by
      oral gavage from gestational day (GD) 6 to lactational day (LD) 20 to groups of
      25 mated females each. Between GD 17 and 20 the high dose was reduced to 2.5
      mg/kg/day because of pup tremors observed at this dose level in a concurrent two
      generation study. Females were allowed to deliver and the young were evaluated
      for survival, growth, development, behavior, and histological changes to brain,
      spinal cord, peripheral nerve, and skeletal muscle. Behavioral assessment of the
      offspring consisted of open field motor activity, auditory startle habituation,
      and passive avoidance tests; each was conducted on weanling and adult animals
      (one animal/sex/litter). Histopathological examination of the CNS and PNS was
      conducted on one animal/sex/litter on postnatal days (PND) 11 and 60. There were
      significant increases in average F0 maternal body weight gains during gestation
      in the 0.6 and 3.6/2.5 mg/kg/day groups, but no other effects were observed in
      pregnant females of these or the low-dose groups during the study. Beginning on
      PND 6, tremors were observed in high-dose pups, and this was followed by hindlimb
      splay in all high-dose pups by PND 15-26. Both of these physical signs
      disappeared by PND 34 (i.e., 10-11 days after weaning). There were no compound
      related deaths in F1 offspring. Beginning on PND 11, progressive decreases in
      preweaning average weights were observed in the high-dose group (to 42% below
      control in females on PND 21). Average weight gain during the postweaning period
      was significantly decreased in the 3.6/2.5 mg/kg/day group. There were EB-related
      effects in behavioral tests only in the high-dose group. A significant increase
      in PND 13 average horizontal motor activity was due to stereotypical movements.
      Average horizontal activity was decreased on PND 17 and in adult females, but
      there was no effects on PND 21. Average peak auditory startle response amplitude
      was decreased on PND 22 and in adults. There were no EB-related effects in the
      passive avoidance test, relative brain weights, or in the histological
      examination (including morphometry) of the nervous system. These results
      demonstrate that the high-dose EB exposure during gestation and lactation to rats
      produced evidence of neurotoxicity in the F1 offspring, and a clear No Observed
      Adverse Effect Level (NOAEL) for developmental neurotoxicity of EB was determined
      to be 0.6 mg/kg/day.

PMID- 9253009
TI  - Neurobehavioral consequences of intermittent prenatal exposure to high
      concentrations of toluene.
AB  - The effects of several concentrations of toluene on physical and behavioral
      development were examined in CD-1 mice prenatally exposed during the last week of
      gestation. Pregnant mice were exposed to either 200, 400, or 2000 ppm toluene
      (TOL) for 60 min three times a day during gestational days 12-17. A sham group
      was exposed concurrently to filtered air. No group differences were observed in
      maternal weight gain or food consumption, common measures of maternal toxicity.
      Initial litter characteristics including gestation length, number of litters
      delivered, and litter size were also similar. At birth, mean initial individual
      pup weight from representative male and female 2000 TOL-exposed pups was less
      than sham-exposed pups; however, entire litter weight did not differ. Pups were
      evaluated on postnatal days 1-20. Pups exposed to 2000 TOL gained less weight and
      performed more poorly on the behavioral tests of the righting reflex, grip
      strength, and inverted screen. In contrast, pups exposed to either 200 or 400 TOL
      did not differ from sham-exposed pups on any of the measures of development or
      behavior. These data provide evidence for the neurobehavioral teratogenicity of
      prenatal exposure to high levels of toluene late in gestation. Because this
      exposure regimen of intermittent high-concentration exposure was designed to
      simulate human exposures that might occur with toluene abuse, these results are
      consistent with case reports of adverse consequences of inhalant abuse by
      pregnant women.

PMID- 9253011
TI  - Behavioral changes following 4-week inhalation exposure to pseudocumene (1,2,4
      trimethylbenzene) in the rat.
AB  - Pseudocumene (1,2,4-trimethylbenzene, TMB) is a component of several solvent
      mixtures. During recent studies on rats we investigated the effect of a 4-week (6
      h/day, 5 days/week) inhalation exposure to TMB at concentrations of 0, 25, 100,
      or 250 ppm on radial maze performance, open field activity, passive avoidance,
      active two-way avoidance, and shock-induced changes in the pain sensitivity
      reflecting the magnitude of the shock-induced fear response (hot plate test). The
      tests were performed between days 14 and 54 after the last exposure. The radial
      maze performance was not disturbed in any dose group. During testing in the open
      field grooming was significantly increased in rats exposed to 100 ppm TMB. In
      rats exposed to 100 and 250 ppm TNB, a foot shock applied after stepping off an
      elevated platform (a safe area) resulted in a significantly smaller increase in
      the step-down latency (i.e., passive avoidance, on days 3 and 7 after the foot
      shock) than in sham-exposed animals. Learning of a two-way active avoidance was
      slightly retarded in rats exposed to 250 ppm of TMB. Results of the hot plate
      test revealed no differences between groups in the paw sensitivity to heat (54.5
      degrees C) before a 2-min intermittent food shock, but in rats exposed to 100 and
      250 ppm of TMB the foot shock-induced fear response persisted apparently longer.
      These results suggest that inhalation exposure to TMB may lead to long-lasting
      disturbances in CNS functions.

PMID- 9253012
TI  - HIV case study.

PMID- 9253013
TI  - Pervasive developmental disorder, not otherwise specified: primary care
      perspectives.
AB  - Pervasive developmental disorder, not otherwise specified (PDD, NOS), a
      developmental-neurologic spectrum disorder, occurs in 10 to 12 of every 10,000
      children. PDD, NOS is characterized by a spectrum of significant problems that
      may vary substantially in range and expression. These may include visual/spatial,
      kinesthetic, verbal/linguistic, and musical/rhythmic problems. Social skill
      deficits are also common, as are restricted, repetitive patterns of behavior,
      interests, and activities. Symptoms of PDD, NOS are often expressed differently
      among children with the disorder and can be mistakenly attributed to other
      problems such as attention deficits, oppositional behavior, or stress reactions.
      Clinicians may encounter children in their practice who exhibit symptoms of PDD,
      NOS and must be familiar with this disorder so that appropriate diagnosis and
      treatment can be provided. Families also need ongoing, anticipatory guidance to
      help them cope with the behavioral aspects of the disorder.

PMID- 9253014
TI  - Chronic fatigue syndrome: an update for clinicians in primary care.
AB  - Cases of long-standing (6 months or longer) fatigue that are not explained by an
      existing medical or psychiatric diagnosis are referred to as chronic fatigue
      syndrome (CFS). CFS is a condition of unknown etiology that presents with a
      complex array of symptoms in patients with diverse health histories. A diagnosis
      of CFS is largely dependent upon ruling out other organic and psychologic causes
      of fatigue. CFS can present the clinician with a unique set of challenges in
      terms of diagnosis and treatment. A review of recent research suggests that the
      management of CFS requires an individualized approach for each patient. An
      historic overview of the condition is presented along with current theories of
      causation, diagnosis considerations, symptom management, and health promotion
      strategies.

PMID- 9253015
TI  - Primary care management of acute low back pain.
AB  - Acute low back pain will affect more than 80% of the population, with more than
      28% of the industrial workforce suffering from lost work. Acute low back pain is
      recognized as the third most common illness presenting to private practice
      groups. The psychosocial overtones of depression and anxiety that often coexist
      or predate the episode of acute low back pain add to its complexity and cost.
      Diagnosis and treatment options are reviewed based on the Agency for Health Care
      Policy and Research recommendations of 1994. This article reviews details of the
      history and physical with emphasis on the importance of a thorough neurologic and
      psychologic evaluation. "Red flags" that should warn the clinician of the
      presence of a more acute illness are discussed with recommendations for referral.
      The treatment of acute low back pain now centers on increasing mobility and
      functional use of the spine as soon as possible. Nonsteroidal anti-inflammatory
      agents as well as aspirin and acetaminophen are recommended as first-line drug
      treatments; they have been found to be equally as effective as muscle relaxants
      and opioids for the control of pain without the burden of dependence and
      potential for abuse.

PMID- 9253016
TI  - Pathophysiology, assessment, and treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) is a slowly progressing neurologic movement disorder
      affecting nearly 1% of the population over age 65. PD is the fourth most common
      neurodegenerative disease of patients. Incidence is greater in men with a ratio
      of 3:2--men to women. Because PD is so complex, diagnosis and treatment are often
      very challenging. While the cause of PD is unknown, research has concentrated on
      genetics, exogenous toxins, and endogenous toxins from cellular oxidative
      reactions. The presenting symptoms of a patient with PD include muscle rigidity,
      tremors, bradykinesia, and postural instability. Treatment for PD has been
      primarily pharmacologic: levodopa, carbidopa, anticholinergics, and selegiline (a
      monoamine oxidase inhibitor to reestablish an equilibrium between dopamine and
      acetylcholine). surgical procedures (e.g., pallidotomy, thalamotomy, and tissue
      implants) are a possible choice of treatment for patients who have failed to
      respond satisfactorily to drugs.

PMID- 9253017
TI  - A comprehensive approach to evaluating nipple discharge.
AB  - While emphasis is justifiably placed on the importance of detecting breast masses
      during breast examination, the equally important need for accurate assessment of
      nipple discharge is often overlooked. Inspection and palpation for nipple
      discharge should be part of every breast examination. When detected, a critical
      analysis should be made of every nipple discharge, with the ultimate objective
      being differentiation between benign and malignant discharges. All nipple
      discharges can be defined by the physical characteristics of laterality,
      spontaneity, color, consistency, number of ducts involved, and duration. By
      correlating these characteristics with certain historical features (e.g., age,
      pregnancy, trauma, drugs), accurate determination of etiology can be made. A four
      step approach is presented that offers a logical method for making the essential
      correlations. The sequence of the four relevant questions proposed gives the
      examiner a logical basis from which to assign clinical importance to each
      discharge. An algorithm is outlined that correlates diagnostic considerations
      with therapeutic actions.

PMID- 9253018
TI  - Counseling children and adolescents on safety.

PMID- 9253019
TI  - Troglitazone: a new class of oral antihyperglycemic for the treatment of type II
      diabetes.

PMID- 9253020
TI  - Symptoms attributed to ovarian cancer by women with the disease.
AB  - Ovarian cancer is more likely to be cured when diagnosed in the early stages, but
      the vagueness of presenting symptoms, which are easily attributed to benign
      conditions, is a major barrier to early diagnosis. The goal of this research was
      to further delineate these vague presenting symptoms. A convenience sample of 50
      women aged 35 to 70 years who had been diagnosed with ovarian cancer was obtained
      through the Internet. Data were obtained by means of a one-time questionnaire
      consisting of a symptom checklist, narrative descriptions of symptoms, and
      demographic questions. Overall, 94% (n = 47) of the participants reported
      experiencing at least one symptom prior to their ovarian cancer diagnosis. Six
      gastrointestinal symptoms were reported by greater than 50% of the sample. The
      mean number of symptoms per woman was 8.6 (SD = 4.3, range 1-190. The mean total
      number of symptoms reported by the women that they retrospectively attributed to
      cancer was 5.9 (SD = 4.5, range 0-16). Narratively, the women reported menstrual
      cycle changes most frequently (22% of the sample). This study highlights the need
      for education of health care professionals on the symptomatology of this disease.
      Education of women should focus on the known signs and symptoms of ovarian cancer
      and what defines normal age-related physiologic changes.

PMID- 9253021
TI  - Electron probe X-ray microanalysis of otoconia in the guinea pig inner ear.
AB  - By using the electron probe X-ray microanalysis technique, the elemental
      composition of otoconia was analyzed in the normal adult pigmented guinea pig. In
      the X-ray spectra of otoconia, the most abundant element was Ca, but significant
      peaks for P, S, Cl and K were also detected. The comparison of the elemental
      composition in the utricular and saccular otoconia did not show any significant
      difference. Regression analysis revealed that the concentrations of Ca and K are
      related by a linear function in both the utricular and saccular otoconia.
      Analysis of otoconia of different sizes showed that there were no differences in
      Ca concentration in small, normal and large otoconia. The comparison of other
      elemental compositions revealed that P, S, Cl and K in the central part of
      saccular small otoconia showed higher concentrations than those of normal or
      large otoconia. P, S, Cl and K in the utricular small otoconia showed relatively
      higher concentrations. These findings may indicate that the small otoconia are
      immature or newly generated.

PMID- 9253022
TI  - The morphological differences of stereocilia and cuticular plates between type-I
      and type-II hair cells of human vestibular sensory epithelia.
AB  - The sensory epithelia of macula utriculi were examined by conventional and
      intermediate voltage transmission electron microscopy. The specimens were
      obtained from three cases of acoustic neurinoma who were operated on using the
      translabyrinthine approach. The mean diameter of the vestibular hair cell
      stereocilia was obtained and the cuticular plates of type-I and type-II hair
      cells were reconstructed three-dimensionally from the consecutive 0.5-micron
      thick sections. The mean diameter of stereocilia of type-I hair cells was 488 +/-
      59 nm (n = 13) and that of stereocilia of type-II hair cells was 373 +/- 21 nm (n
      = 14). Stereocilia of type-I hair cells numbered about 70 and those of type-II
      hair cells about 50. The cuticular plates of type-I hair cells were several times
      as thick as those of type-II hair cells. The cuticular plate of the type-I hair
      cell appeared to be an inverse cone and that of the type-II hair cell seemed to
      be a flat disc.

PMID- 9253023
TI  - Clinical testing of the statolith-ocular reflex.
AB  - Quantification of eye torsion induced by stimulation of the statolith organ has
      recently become available (in the clinic) thanks to the development of video
      nystagmography. A major step forward has been the development of real-time
      measurement of eye torsion which enables interactive testing of the statolith
      ocular reflex. The function of the statolith organs can be evaluated by the study
      of the impact of statolith stimulation upon the canal-mediated dynamic vestibulo
      ocular reflex (VOR) or by measurement of the static VOR. The latter is more
      appropriate because instruction or alertness seems not to affect the reflex
      substantially. Four ways of inducing the static reflex are discussed and related
      experiments are described. In normal subjects, the gain of eye torsion upon
      lateroflexion (up to 45 degrees) and whole-body roll (up to 90 degrees) ranges
      from 0.13 to 0.22; eye torsion is 10.3 degrees maximal. Eccentric rotation
      inducing a maximal centrifugal force of 1 g results in a gain of eye torsion
      ranging from 0.15 to 0.23 with a maximal eye torsion of 7.8 degrees in normals.
      Sinusoidal sideward translation at accelerations of about 0.5 g at 0.3 Hz, which
      can be considered as specific dynamic statolith stimulation, induces a small but
      substantial eye torsion of maximally 4.1 degrees and with an eye torsion gain
      ranging from 0.10 to 0.15. Lateroflexion and body flexion do not require
      sophisticated stimulation equipment and therefore are attractive for
      implementation in the out-patient department. In patients, impairment of the
      statolith-ocular reflex is frequently found both in patients with normal as well
      as in those with defective dynamic VORs (caloric asymmetries). A qualitative
      concept is presented to describe the deflection pattern of the cilia upon
      lateroflexion, eccentric rotation and sidewards translational acceleration.
      According to this theoretical concept, a reduced static eye torsion might point
      to both a saccular and/or an utricular lesion. An asymmetry of ocular torsion is
      only expected upon eccentric rotation or sidewards translation in case of a
      unilateral saccular lesion.

PMID- 9253024
TI  - Selective chemical vestibulectomy. Preliminary results.
AB  - In an attempt to destroy the peripheral vestibular labyrinth selectively in
      patients suffering from intractable vertigo as a result of end-stage Meniere's
      disease, 25 patients underwent selective chemical vestibulectomy between 1989 and
      1994. As part of the procedure a certain quantity of streptomycin was placed
      between the bony and the membranous part of the lateral semicircular canal. The
      dosage of streptomycin used for successful ablation of vertigo varied between 250
      and 100 micrograms. Within 12 months following the procedure all patients
      experienced a tremendous improvement in their overall condition. In spite of the
      fact that some patients noted an overall hearing improvement, increased cochlear
      thresholds were observed in a number of patients, which could not be ignored. The
      aim of this report is to detail the reliability of control of vertigo,
      conservation of hearing, and change in disability 12 months after surgery in the
      23 patients (of 25) available for follow-up.

PMID- 9253026
TI  - Temporal bone pathology of a patient with cochlear implant.
AB  - A 66-year-old man with profound total deafness received a 22-channel cochlear
      implant. After surgery, his hearing improved and the postoperative course was
      uneventful except transient vertigo. The patient died of lung cancer after 2.5
      years. Twelve hours after death, the temporal bone was harvested for histological
      and electron microscopic examination. The mastoid air cells were preserved,
      although a few mucosal folds were present. The Dacron mesh tie had largely been
      absorbed, but part remained embedded in fibrous tissue. No inflammation was noted
      in the tympanic cavity or the round window through which the electrodes were
      inserted. In the cochlea, the scala tympani was filled with fibrous tissue at the
      site of electrode insertion. The scala media had collapsed, while the organ of
      Corti and stria vascularis showed degeneration. Osseous spiral bundles and spiral
      ganglion cells were noted, though reduced in number.

PMID- 9253025
TI  - Molecular basis of type II collagen autoimmune disease: observations of
      arthritis, auricular chondritis and tympanitis in mice.
AB  - A type II collagen autoimmune response results in arthritis, auricular chondritis
      and tympanosclerosis in humans and animals. The purpose of this study is to
      further define the molecular and pathogenic events involved in these lesions in
      rodents. Type II collagen fragment CB11-specific monoclonal antibodies induced
      lesions in joints, ear lobes and tympanic membranes. In immunized mice, the
      thickness of tympanic membranes increased to two- to fourfold normal size.
      Electron micrography showed that the arrangement of collagen fibers is irregular
      in both radial and auricular layers, containing fibroblasts, a homogeneous
      material resembling low-density cholesterol crystals and cell infiltration. The
      mice with auricular chondritis had lymphocytes expressing V beta-8 T cell
      receptor (TCR) in arthritic joints and lymphocytes expressing V beta-6 TCR in ear
      lobe lesions. A monoclonal antibody specific to the TCR V beta-8 subfamily
      suppressed the onset of arthritis. Sequence analyses of the V beta structure of
      TCR involved in the lesions confirm the immunohistologic study.

PMID- 9253027
TI  - Laryngeal zoster with unilateral laryngeal paralysis.
AB  - The case of a 60-year-old man with a unilateral laryngeal mucosal lesion and
      complete left vocal cord paralysis is reported. The lesion localized to the left
      side of the larynx covered the laryngeal vestibule, arytenoid, false vocal cord
      and true vocal cord, but did not extend to the hypopharynx or oropharynx. Enzyme
      immunoassay for varicella-zoster virus (VZV) led to a diagnosis of VZV infection.

PMID- 9253028
TI  - Sternocleidomastoid muscle-clavicle myoosseous flap for single-stage
      reconstruction of postoperative tracheal defects in patients with invasive
      thyroid tumor. Three case reports.
AB  - In this report, we present 3 cases with thyroid carcinoma with tracheal invasion.
      In all cases, the tracheal defects were simultaneously reconstructed using a
      sternocleidomastoid muscle-clavicle myoosseous flap. We were able to close the
      tracheostomas without trouble, and no stenotic lesions or late complications were
      noted. This myoosseous composite flap has proved itself to be a reliable material
      for laryngotracheal reconstruction in some cases with thyroid carcinoma.

PMID- 9253029
TI  - Direct evidence that iron deprivation induces apoptosis in murine lymphoma 38C13.
AB  - We found that the mouse B cell lymphoma 38C13 underwent apoptosis in vitro when
      deprived of iron by three independent methods: (1) exposure to a synergistic pair
      of rat IgG monoclonal antibodies against the mouse transferrin receptor; (2)
      exposure to the iron chelator deferoxamine (DFO), and (3) exposure to a defined
      culture medium without any added iron (iron-poor medium). When each antibody was
      present at a concentration of 5 micrograms/ml, the number of living cells
      declined to approximately 25% after a 24-hour incubation. After 48 h, there were
      no surviving cells. When DFO was present at a concentration of 10 microM, the
      effects were similar, but delayed by 24 h. when iron-poor medium was used, the
      effects and kinetics were similar to those seen with antibody treatment. For each
      method of iron deprivation, the reduction in cell viability correlated with the
      development of apoptosis, as assessed by DNA fragmentation analysis and propidium
      iodide staining. Electron microscopy studies provided additional confirmation of
      apoptotic cell death. The addition of 500 microM ferric citrate completely
      prevented apoptosis for each of the three methods of iron deprivation. These
      studies provide new and compelling evidence to support the view that iron
      deprivation can specifically induce apoptosis and serve to strengthen the
      rationale for further studies of iron deprivation as a form of cancer treatment.

PMID- 9253030
TI  - Influenza A virus affects the response of human peripheral blood mononuclear
      cells to phytohaemagglutinin A by altering the cytoskeleton.
AB  - In the present study, we demonstrate that the infection of human peripheral blood
      mononuclear cells (PBMC) with influenza A virus caused changes in intracellular
      fluorescein fluorescence polarization (IFFP) which, as previously described,
      reflect alterations in the polymerization of the cytoskeleton. Kinetic
      measurements revealed two cycles of an approximate 10% decrease in IFFP within
      3.5 and 5 h after infection. Infection win influenza A virus also altered the
      response of PBMC to phytohaemagglutinin (PHA), which was manifested as changes of
      5.3 and 4% in IFFP at 1 and 2 h after infection, respectively. the changes in
      IFFP correlated with DNA synthesis measured 72 h after exposure to PHA. These
      results show the ability of IFFP measurements to identify early intracellular
      metabolic events induced in virus-infected cells.

PMID- 9253031
TI  - Role of steroid hormone and growth factor receptors and proto-oncogenes in the
      behavior of human mammary epithelial cancer cells in vitro.
AB  - The cultivation of cells from primary breast cancers is very unpredictable. The
      majority of breast-cancer-derived cell lines are of metastatic origin. To define
      the characteristics of tumor cells which govern their ability to grow in vitro as
      primary cultures as well as continuous or established culture cell lineages,
      human mammary epithelial cancer (HMEC) cells from 18 cases of unselected primary
      breast cancer were propagated in culture. Propagation of HMEC cells in vitro as
      monolayers in primary culture was successful in 10 out of 18 (55.5%) cases, which
      showed continous proliferation of tumor cells only up to 6-8 passages before they
      reached senescence. An investigation of the effects of phenotypic expression of
      estrogen receptors (ER), the progesterone receptors, c-erbB-2 oncoprotein and
      epidermal growth factor receptors (EGFR) on the capacity of HMEC cells to grow in
      vitro as monolayers showed that expression of ER and EGFR is required for
      controlling tumor proliferative activity in vitro. Expression of ER protein made
      the growth of HMEC cells more difficult, while expression of EGFR protein made
      their growth in vitro easier. Phenotypic characteristics of floating HMEC cells
      were found to be different from those grown on cover slips as adherent cultures,
      suggesting a selective growth of HMEC cells of a specific phenotype in culture.
      Cultured HMEC cells in subsequent passages showed a decrease in their
      proliferative capacity, alterations in phenotypic characteristics and development
      of morphologic features of terminal differentiation, resulting in senescence.

PMID- 9253032
TI  - Uniform expression of cytotoxic molecules in anaplastic large cell lymphoma of
      null/T cell phenotype and in cell lines derived from anaplastic large cell
      lymphoma.
AB  - We recently provided ample evidence that anaplastic large cell lymphomas of
      T/null phenotype (T-/null-ALCL) genotypically represent peripheral T cell
      lymphomas which in up to 90% have a phenotype of cytotoxic cells with expression
      of granzyme B protein and perforin transcripts. However, the issue of granzyme B
      expression in T-/null-ALCL is still controversial due to differing results from
      another laboratory. To verify our earlier immunohistochemical stainings for
      granzyme B, we looked for granzyme B transcripts by in situ hybridization (ISH).
      In addition, we investigated our previously analyzed cases by immunohistology
      (IH) with another antibody (2G9), which reacts with two molecules known to be
      expressed in cytotoxic cells: T-cell-restricted intracellular antigen (TIA)-1 and
      granule membrane protein-17 (GMP-17). We also extended our studies to homogenous
      tumor cell populations provided by ALCL-derived cell lines. As evidenced by ISH,
      transcripts for perforin, TIA-1 and granzyme B were found in all ALCL-derived
      cell lines. Similarly, proteins of TIA-1/GMP-17, granzyme B and perforin were
      expressed in all of these lines as shown by IH. In biopsy specimens, TIA-1/GMP-17
      were detected by IH in 14/16 cases of T-/null-ALCL, and granzyme B transcripts
      were found in 13/13 T-/null-ALCL cases, but not in 6 B-ALCL cases. The detection
      of granzyme B transcripts yielded results largely identical to those of IH for
      granzyme B protein, thus confirming our earlier data and suggesting that the
      regulation of the expression of this molecule largely occurs at the
      transcriptional level. Our data further confirm the almost uniform expression of
      cytotoxic molecules in both primary ALCL cases and ALCL-derived cell lines and
      therefore suggest that the derivation from cytotoxic T cells may be the unifying
      characteristic for T-/null-ALCL.

PMID- 9253033
TI  - Activated naive and memory CD4+ and CD8+ subsets in different stages of HIV
      infection.
AB  - The aim of this study was to evaluate the changes and the correlations between
      the main lymphoid phenotypes indicative of activation and/or functional states
      during the course of HIV infection. Immunophenotype studies by flow cytometry
      were performed on blood samples from 59 HIV-1-positive patients, divided into
      four stages, and 18 seronegative healthy controls, to determine the expression of
      HLA-DR, CD29 and CD45RA on CD4+ and CD8+ lymphocytes. HLA-DR expression was
      elevated on the total lymphocyte population and in both the main T subsets. Its
      presence on CD4+ lymphocytes probably has a different significance in the first
      phase of infection when it is indicative of reactive activation, in contrast to
      the more advanced stages of disease when it favors the spread of HIV infection
      among this cellular subset. The increasing state of immune activation is also
      confirmed by a proportional decrease in the expression of CD45RA, substantial
      stability of CD29 and an increase in double-negative CD4+ cells as the infection
      proceeds. Also CD8+HLA-DR+ lymphocytes increase during the course of disease. The
      parallel increase of the CD8+CD45RA+ subset in asymptomatic patients suggests the
      presence in this phase of infection of peripheral blood immature and activated
      CD8+ cells. Similarly to CD4+, the CD29 subset of CD8+ lymphocytes remains
      unchanged compared to controls during disease progression. In both CD4+ and CD8+
      subsets we observed the increase of a double-negative sub-population of uncertain
      significance. HLA-DR, the memory marker CD29 and the naive marker CD45RA seem to
      be the more promising and helpful indicators for a better staging of disease and
      may provide information that accurately correlates with progression of infection.
      The peculiar trend of the described phenotypic alterations could represent
      changes in the immune response to HIV during disease progression and facilitate
      the definition of specific immune patterns in different stages of HIV infection.

PMID- 9253034
TI  - Increased expression of cytokeratins 14, 18 and 19 correlates with tumor
      progression in the uterine cervix.
AB  - The expression of cytokeratins (CKs) in normal cervical epithelium, low grade
      squamous intraepithelial lesions (SIL), high grade SILs and squamous cell
      carcinoma (SCC) were analyzed using four different monoclonal antikeratin
      antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity
      in basal and parabasal layers. CK 19 and 14 were expressed only in the basal
      layer while CK 13 was found selectively n the spinal cells. As the lesions
      progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19
      and 14 in the basal cell compartment increased while the expression of CK 13
      decreased. In SCC, as well-differentiated tumors showed decreased
      immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal
      (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13
      reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14
      may be directly related to tumor grade and CK 13 may be a marker of
      differentiation in cervical lesions.

PMID- 9253035
TI  - Expression of the antiapoptotic protein bcl-2 is not dependent on the tumor
      suppressor p53 protein in Indian breast carcinoma.
AB  - Tissue homeostasis and the maintenance of cell populations depend on a delicate
      balance between the rates of cell proliferation and cell death. Programmed cell
      death or apoptosis is believed to play a major role in physiological processes
      which, when defective, could contribute to the pathogenesis and progression of
      tumors. A role for altered programmed cell death in cancer stems from the
      description of alterations on tumor-associated genes involved in the regulation
      of apoptosis such as p53 and bcl-2. The p53 gene promotes apoptosis in cells with
      genetic damage, while bcl-2 is an antiapoptotic gene. It is therefore possible
      that the balance between p53 and bcl-2 may have significant implications for the
      pathobiology of breast cancer. This study was therefore undertaken to evaluate
      the expression of these two proteins with opposite functions and their relation
      to the total growth fraction of the tumor as measured by PCNA immunoreactivity. A
      significant correlation was observed between expression of p53 and PCNA. In
      contrast, bcl-2 expression did not correlate with the expression of p53. There
      was also no correlation observed between expression of bcl-2 and PCNA. A
      significant correlation was observed between expression of p53 and the grade of
      the tumor and stage of the disease. Our results thus support the hypothesis that
      accumulation of p53 is associated with a high tumor proliferation rate, an
      association that might be expected in view of the role of wild-type p53 as a
      negative regulator of cell proliferation. Another important observation was the
      lack of relationship between bcl-2 expression and PCNA immunoreactivity,
      supporting the hypothesis that bcl-2 is not a major regulator of proliferation.

PMID- 9253036
TI  - Medical applications of synchrotron radiation x-rays.
AB  - The use of synchrotron radiation is not widespread in the field of medicine and
      in fact few health-care professionals have even heard of it. It is the purpose of
      this article to explain what it is and to give some examples of how it can
      contribute to medical science. X-rays have been used for diagnostic medical
      imaging for more than 100 years and, whilst new techniques such as computed
      tomography have been developed, the means of producing x-rays has altered little
      during that time. Synchrotron radiation sources provide multiple, extremely
      intense and tuneable beams of photons over a huge range of energies from infrared
      through to hard x-rays. Their advent has revolutionized many experimental
      techniques and synchrotron radiation is being applied across many fields from
      imaging to molecular dynamics. It has spawned several methods for studying live
      and wet tissue samples, yielding information on both structure and composition on
      all length scales down to atomic resolution. Such techniques have played a
      crucial role in the development of molecular biology and the solution of protein
      structures. The application of synchrotron radiation in the field of radiography
      is now expanding and it is clear that very substantial improvements in image
      quality and patient dose can be realized. Following an overview of the production
      and properties of synchrotron radiation, some of the ways in which this
      remarkable tool has already been exploited for medical research are reviewed and
      some potential clinical opportunities highlighted.

PMID- 9253037
TI  - Anisotropy of human muscle via non-invasive impedance measurements.
AB  - Combining non-invasive 50 kHz impedance measurements with a mathematical model
      for the underlying structure, we obtain in vivo values for the transverse and
      longitudinal conductivities of the muscles of the human thigh and for the
      (isotropic) conductivity of the covering skin-fat layer. Results for a healthy
      male subject are in acceptably good agreement with those obtained elsewhere on
      surgically exposed or freshly excised animal tissue and with 'global'
      measurements on humans. Also, measurements using rotatable probes reveal
      orientations of underlying muscle fibres via minima in resistance versus angle
      curves. The results suggest potentially useful methods for studying muscle
      properties in clinical and physiological research.

PMID- 9253038
TI  - Erythemal irradiances of filtered ultraviolet radiation.
AB  - A spectrum evaluator (3 cm x 3 cm) employing four passive dosimeters has been
      used to evaluate the time averaged spectrum to allow calculation of the erythemal
      exposures resulting from the predominantly UVA component of filtered solar
      ultraviolet radiation. An exposure interval of approximately 20 min to autumn and
      spring sunshine was required for the spectrum evaluator to allow evaluation of
      the filtered source spectrum. For a clear spring day an erythemal exposure of
      0.85 MED (minimum erythemal dose) to a horizontal plane and 0.38 MED to a
      vertical plane over a 6 h period was measured within a glass enclosure. For a
      partially cloudy day six weeks later, these were 0.89 and 0.44 MED for the
      horizontal and the vertical planes respectively. The ratios of the filtered to
      the unfiltered erythemal exposures within and outside the enclosure respectively
      ranged from 0.08 to 0.18 throughout the two days.

PMID- 9253039
TI  - External audit of photon beams by mailed film dosimetry: feasibility study.
AB  - A feasibility study for mailed film dosimetry has been performed. The global
      reproducibility of the method is better than 2%. It is shown that the normalized
      sensitometric curve does not depend on photon beam quality in the range from Co
      60 gamma-rays to 18 MV x-rays, although the dose per optical density decreases
      when the energy increases. The fading of the latent image before film processing
      is only 3% per month and the normalized sensitometric curve is not modified after
      a period of 51 days between irradiation and processing. Sets of films were mailed
      to three different institutes for irradiation and returned for processing and
      evaluation after more than two months in order to verify that mailing of
      irradiated and unprocessed films does not produce unwanted artefacts. Finally the
      feasibility of external audits with mailed film dosimetry is illustrated by
      comparison of beam profiles measured with films and ionization chambers in a
      polystyrene phantom.

PMID- 9253041
TI  - Fluence non-uniformity effects in air kerma determination around brachytherapy
      sources.
AB  - In ionization chamber dosimetry close to brachytherapy sources, the non-uniform
      photon fluence in the vicinity of the air cavity of the ionization chamber must
      be corrected for. In this paper, experimentally determined relative non
      uniformity correction factors are determined for a PTW23331 chamber and a number
      of Farmer-type chambers. It is concluded that the 'anisotropic' theory of
      Bielajew agrees better with the experimental results than the 'isotropic' theory
      of Kondo and Randolph. The experiments show that neither the material choice nor
      the radius of the central electrode have any significant effect on the non
      uniformity correction factors. Experiments on the wall-material dependence in the
      non-uniformity correction factor, which is predicted by the anisotropic theory,
      were inconclusive. Parameters for the Farmer-type chambers for calculation of
      theoretical non-uniformity correction factors are given. Data to derive
      anisotropic fluence non-uniformity correction factors are given in tabular form.
      An error in the Kondo and Randolph equations is reported and the corrected
      equations presented.

PMID- 9253040
TI  - New compensator design options for charged-particle radiotherapy.
AB  - The purpose of this investigation is to propose new compensator design strategies
      for protons and heavier particles which are based on pencil-beam (PB) dose
      calculations and which significantly reduce the dose to tissues downstream from
      the target, yet provide acceptable target coverage under conditions of patient
      motion. Averaging and expansion operations are provided to improve the target
      coverage if the patient moves slightly during treatment, and a structure-sparing
      option is provided to protect critical structures lying downstream from the
      target. The new compensator design options were evaluated for two patients who
      had skull-base tumours. When the patient and compensator were perfectly aligned,
      the new PB compensator designs provided target coverage comparable to, if not
      better than, standard compensator designs for both patients. Furthermore, the
      volume of normal tissue distal to the target which received in excess of 95% of
      the prescription dose was roughly a factor of two lower for the averaged PB
      compensators than for the expanded standard compensators. In the event of patient
      motion, on average, the volume of the target receiving 95% or more of the
      prescribed dose was 3% less for the averaged PB compensators than for the
      expanded standard compensators. In conclusion, the new compensator design options
      evaluated in this investigation provide better protection for normal tissues
      distal to the target volume than standard compensator designs, with only a modest
      decrease in target volume coverage in the event of patient motion.

PMID- 9253042
TI  - An EGS4 Monte Carlo examination of general cavity theory.
AB  - EGS4 Monte Carlo simulations have been performed to examine general cavity theory
      for a number of TLD cavity materials irradiated in megavoltage photon and
      electron beams. The TLD materials were LiF, Li2B4O7, CaF2 and CaSO4 irradiated in
      Perspex, water, Al, Cu and Pb phantoms. For megavoltage photon beams, this has
      been done by determining the dose component (1-d) resulting from photon
      interactions in the cavity compared with the dose component resulting from photon
      interactions in the phantom material (d) by Monte Carlo simulations and
      analytical techniques. The results indicate that the Burlin exponential
      attenuation technique can overestimate the dose contribution from photon
      interactions in a 1 mm thick LiF cavity by up to 100% compared with the Monte
      Carlo results for LiF TLDs irradiated in a water or Perspex phantom. However,
      there is agreement to within 1% in the quality dependence factor, determined from
      Burlin's cavity theory, Monte Carlo simulations and experimental measurements for
      LiF and Li2B4O7 TLDs irradiated in a Perspex or a water phantom. The agreement
      was within 3% for CaF2 TLDs. However there was disagreement between Monte Carlo
      simulations and Burlin's theory of 6 and 12% for LiF TLDs irradiated in copper
      and lead phantoms respectively. The adaptation of Burlin's photon cavity theory
      and other modifications to his photon general cavity theory for electrons have
      been shown to be seriously flawed.

PMID- 9253043
TI  - Application of cavity theory to the response of various TLDs to 60Co gammas
      degraded in water.
AB  - Several types of thermoluminescent dosimeters (LiF:Mg, Ti, Al2O3:Mg,Y and
      CaF2:Mn) were irradiated at different depths in a water phantom placed at a
      distance of 2.5 m from a panoramic 60Co source. Detectors were encapsulated in
      Plexiglas holders with a wall thickness of 0.5 cm. Reference dosimetry was
      carried out using a Fricke dosimeter and an ionization chamber. The experimental
      data were compared with the predictions of the general cavity theory for gamma
      ray spectra at different depths of water. The suitability of parameters of the
      cavity theory proposed by different authors was evaluated in the analysis of the
      experimental results. The results show that there is no need for any modification
      to the original and simple Burlin expression which gives very good agreement with
      the experimental values.

PMID- 9253044
TI  - Evaluating x-ray detectors for radiographic applications: a comparison of
      ZnSCdS:Ag with Gd2O2S:Tb and Y2O2S:Tb screens.
AB  - ZnSCdS:Ag was evaluated as a radiographic image receptor and was compared with
      Gd2O2S:Tb and Y2O2S:Tb phosphors often used in radiography. The evaluation of a
      radiographic receptor was modelled as a three-step process: (i) determination of
      light output intensity as related to the input radiation dose, (ii) determination
      of visible light characteristics with respect to radiographic optical detectors,
      and (iii) determination of image information transfer efficiency. The light
      intensity emitted per unit of x-ray exposure rate was measured and theoretically
      calculated for laboratory prepared screens with coating thicknesses from 20 to
      220 mg cm-2 and tube voltages from 50 to 250 kVp. ZnSCdS:Ag light intensity was
      higher than that of Gd2O2S:Tb or Y2O2S:Tb for tube voltages less than 70 and 80
      kVp respectively. ZnSCdS:Ag displayed the highest x-ray to light conversion
      efficiency (0.207) and had optical properties close to those of Gd2O2S:Tb and
      Y2O2S:Tb, and its emission spectrum was well matched to optical detectors. The
      image information transfer properties described by the modulation transfer
      function, the quantum noise transfer function, and the detective quantum
      efficiency were calculated for both general radiographic and mammographic
      conditions and were found to be intermediate between those of Gd2O2S:Tb and
      Y2O2S:Tb screens. Conclusively, ZnSCdS:Ag is an efficient phosphor well suited to
      radiography.

PMID- 9253045
TI  - Monochromatic microtomographic imaging of osteoporotic bone.
AB  - A monochromatic beam obtained from laboratory based instrumentation has been used
      for the first time to carry out a microtomographic x-ray scan of a small segment
      of osteoporotic bone. The resulting tomograph provides an accurate map of the x
      ray linear attenuation coefficient at the characteristic energy for Cu K alpha x
      rays. The bone segment was imaged in a variety of ways which are common to
      microtomography in order to compare the efficacy of different experimental
      configurations. A Si crystal monochromator was placed before the x-ray detector
      in order to reject radiation scattered by the sample. In addition, polychromatic
      scans were compared with monochromatic scans. The effects of multiple scatter can
      be seen upon comparison of scans with and without the second monochromator. The
      results indicate that beam-hardening and x-ray scattering can significantly alter
      an image, thereby distorting the interpretation of what is physically present in
      the specimen. An accurate, monochromatic tomographic scanning facility is being
      developed in an attempt to map meaningful physical constants for various
      materials.

PMID- 9253046
TI  - Design and calibration of electric field probes in the range 10-120 MHz.
AB  - In view of potential thermal hazards, there is a need to determine the specific
      absorption rate (SAR) distributions associated with radiofrequency coils used in
      magnetic resonance imaging (MRI) (typically 10-120 MHz). Electric field (E-field)
      distributions in tissue-equivalent phantoms may be determined using a probe
      comprising a dipole antenna and a detector. The geometry of the dipole dictates
      the sensitivity of the device, thus two designs are discussed in this paper. Both
      probes are compact, have a spatial resolution of 2.5 cm3, operate at MR
      frequencies and have a response independent of the dielectric characteristics of
      the phantom material. Calibration of these probes requires a system capable of
      producing a known E-field both in air and in a tissue-like medium at frequencies
      between 10 and 120 MHz. Transverse electromagnetic wave (TEM) cells answering
      these specifications are described and the calibration procedure outlined.
      Accurately calibrated E-field probes can make field measurements in phantoms
      which can be used to verify predictions from numerical models. These numerical
      techniques may then be used to predict E-fields, and hence SAR, in patients.

PMID- 9253047
TI  - Experimental verification of numerically predicted electric field distributions
      produced by a radiofrequency coil.
AB  - There are safety issues regarding energy deposition within tissues due to
      radiofrequency fields used in some magnetic resonance (MR) procedures. Procedures
      should be compliant with guidelines that specify limits to temperature elevation
      and specific absorption rate (SAR). In general, direct measurement of these
      quantities in patients is impractical and an alternative approach is to determine
      SAR from the electric field (E-field) distributions predicted by numerical
      models. In this initial study the E-field distribution in a tissue-simulating
      phantom due to a square coil driven at 31 MHz is predicted using a finite
      difference time domain (FDTD) solution to Maxwell's equations. An experimental
      arrangement of the same problem was constructed and the resulting E-field
      distribution was measured using a calibrated minimally perturbing E-field probe.
      A comparison between experimentally and theoretically derived data showed that
      the numerically predicted E-fields were within +/-1 dB of the fields measured
      with the E-field probe in the phantom material. The results provide confidence in
      the use of the FDTD algorithm to determine quantitatively accurate E-field
      distributions arising from square radiofrequency (RF) coils used in MR
      procedures. The accuracy of numerical models of other coil designs such as bird
      cages, saddles and surface coils can be investigated in the same manner. Future
      studies will evaluate the exposure of patients to these RF fields.

PMID- 9253048
TI  - Gamma-ray scattering for fat fraction measurement.
AB  - The work reported examines the potential of using gamma-ray photon backscatter
      information to measure in vivo the percentage of fat in specific tissue volumes.
      241Am gamma rays are used as the source and the backscatter detected with a
      hyperpure germanium detector, with ethanol (approximately 80% fat, 20% muscle)
      and water (muscle) being used as tissue substitutes. Two measurement techniques
      are examined; the measurement of the ratio of coherent scatter to Compton scatter
      and the measurement of the Compton scatter profile. Both are shown to be
      sensitive to the composition difference between ethanol and water. For the
      coherent-Compton scatter ratio, the measured difference between water and ethanol
      is 1.85:1, close to the value calculated (about 2:1). A similar difference in the
      coherent-Compton ratios between muscle and fat is calculated (2.2:1). The FWHM of
      the Compton profile has also been shown to vary with tissue composition with a
      difference of 0.10 keV (5%) between the ethanol and water profile widths.

PMID- 9253049
TI  - An optical phantom with tissue-like properties in the visible for use in PDT and
      fluorescence spectroscopy.
AB  - The design and characterization of optical phantoms which have the same
      absorption and scattering characteristics as biological tissues in a broad
      spectral window (between 400 and 650 nm) are presented. These low-cost phantoms
      use agarose dissolved in water as the transparent matrix. The latter is loaded
      with various amounts of silicon dioxide, Intralipid, ink, blood, azide,
      penicillin, bovine serum, and fluorochromes. The silicon dioxide and Intralipid
      particles are responsible for the light scattering whereas the ink and blood are
      the absorbers. The penicillin and the azide are used to ensure the conservation
      of such phantoms when stored at 4 degrees C. The serum and fluorochromes, such as
      Coumarin 30, produce an autofluorescence similar to human tissues. Various
      fluorochromes or photosensitizers can be added to these phantoms to simulate a
      cancer photodetection procedure. The absorption and fluorescence spectroscopy of
      the porphyrin-type fluorescent markers used clinically for such photodetection
      procedures is similar in these phantoms and in live tissues. The mechanical
      properties of these gelatinous phantoms are also of interest as they can easily
      be moulded and reshaped with a conventional cutter, so that complex structures
      and shapes, with different optical properties, can be designed. The optical
      properties of these phantoms were determined between 400 and 650 nm by measuring
      their effective attenuation coefficient (mu eff) and total reflectance (Rd). The
      microscopic absorption and reduced scattering coefficients (mu a, mu s') were
      deduced from mu eff and Rd using a Monte Carlo simulation.

PMID- 9253050
TI  - Array detection for speckle reduction in optical coherence microscopy.
AB  - This paper introduces a spatial-diversity method for speckle suppression in
      optical coherence microscopy. The method is based on combining interference
      signals from an array of detectors placed in the back focal plane of the
      objective lens, such that elements receive light backscattered from the sample
      volume at different angles. Incoherently adding ('compounding') the signals
      increases the signal-to-noise ratio of the processed image compared to that
      attainable with a single detector. The speckle-reduction method was demonstrated
      with a benchtop microscope equipped with a quadrant photodiode. To evaluate its
      potential application in dermatology, images of living skin acquired with and
      without compounding were compared. The quality of the compounded images was found
      to be substantially better. A signal-to-noise gain close to a factor of two (the
      theoretical maximum attainable using four detectors) was achieved without a
      significant loss in resolution. The method can be applied to arrays with a larger
      number of elements, potentially enabling more advanced forms of spatial-diversity
      and adaptive-optics methods.

PMID- 9253051
TI  - Numerical calculation of energy deposition by high-energy electron beams: III-B.
      Improvements to the 6D phase space evolution model.
AB  - The phase space evolution model of Huizenga and Storchi, Morawska-Kaczynska and
      Huizenga and Janssen et al has been modified to (i) allow application on
      currently available computer equipment with limited memory (128 Megabytes) and
      (ii) allow 3D dose calculations based on 3D computer tomographic patient data.
      This is a further development aimed at the use of the phase space evolution model
      in radiotherapy electrons beam treatment planning. The first modification regards
      the application of depth evolution of the phase space state combined with an
      alternative method to transport back-scattered electrons. This depth evolution
      method requires of the order of 15 times less computer memory than the energy
      evolution method. Results of previous and new electron transport methods are
      compared and show that the new electron transport method for back-scattered
      electrons hardly affects the accuracy of the calculated dose distributions. The
      second modification regards the simulation of electron transport through tissues
      with varying densities by applying distributed electron transport through
      similarly composed media with a limited number of fixed densities. Results of non
      distributed and distributed electron transport are compared and show that the
      distributed electron transport method hardly affects the accuracy of the
      calculated dose distributions. It is also shown that the results of the new dose
      distribution calculations are still in good agreement with and require
      significantly less computation time than results obtained with the EGS4 Monte
      Carlo method.

PMID- 9253052
TI  - Accuracy of geometrical modelling of heat transfer from tissue to blood vessels.
AB  - We have developed a thermal model in which blood vessels are described as
      geometrical objects, 3D curves with associated diameters. Here the behaviour of
      the model is examined for low resolutions compared with the vessel diameter and
      for strongly curved vessels. The tests include a single straight vessel and
      vessels describing the path of a helix embedded in square tissue blocks. The
      tests show the excellent behaviour of our discrete vessel implementation.

PMID- 9253053
TI  - Improvements in the design of linear diffusers for photodynamic therapy.
AB  - The angular radiance distribution of several linear diffusers used for
      photodynamic therapy (PDT) was measured. The forward scattering found previously
      was not observed for these designs. The improved isotropy leads to a better
      agreement between intended treatment site and actual maximum of the fluence rate
      profile when the linear diffuser is used in a hollow, cylindrical organ.

PMID- 9253054
TI  - Abutment region dosimetry for sequential arc IMRT delivery.
AB  - Arc-based intensity modulated radiation therapy (IMRT) planning and delivery is
      available as a commercial product (Nomos Corp.). The dose distribution is
      delivered to 1.68 cm thick regions, and the patient moved in a precise manner
      between treatments. Assuming accurate patient positioning, the abutment region
      dose distribution near the gantry isocentre is delivered with no undesired dose
      heterogeneities. However, for regions far from the isocentre, the dose
      distribution may exhibit high- or low-dose regions due to uncompensated beam
      divergence for arc treatments of less than 360 degrees gantry angle length. A
      study has been initiated to characterize abutment region dose distribution
      heterogeneities for sequential arc IMRT delivery. Five dose distributions were
      optimized, each using 8 cm diameter target volumes at different distances from
      the isocentre, and the arc delivery limited to 290 degrees symmetric about the
      vertical axis. The target lengths were sufficient to require a treatment
      consisting of five couch positions, yielding four abutment regions. The dose
      within the abutment regions was measured using film and analysed as a function of
      off-axis position along both the vertical and horizontal directions. Little
      dependence on the dose heterogeneity was seen along the horizontal axis passing
      through the isocentre. However, the abutment regions along the vertical axis
      contained 15% low and 7% high doses at 7 cm above and below the isocentre
      respectively. This dose heterogeneity is not predicted by the current clinical
      release of the treatment planning software due to limitations of the dose
      calculation algorithm. The intensity of dose heterogeneity is considered
      sufficient to warrant further study.

PMID- 9253056
TI  - Radiographic appearance of interstitial lung disease.
AB  - Interstitial lung disease has many forms, and its appearance can vary widely
      under radiographic imaging. This article reviews the anatomy and physiology of
      the lung, then describes the most common radiographic characteristics of ILD-the
      ground glass effect, consolidation, cysts, honey-combing, pulmonary nodules and
      interstitial thickening. Also included is a discussion of the advantages of using
      high-resolution computed tomography to image ILD.

PMID- 9253055
TI  - Dielectric properties of the skin.

PMID- 9253057
TI  - Types of diaphragmatic motion during hepatic angiography.
AB  - To determine the types and causes of diaphragmatic motion during hepatic
      angiography, the authors used transarterial cut-film portography (TAP) to study
      movement of the diaphragm during breath-holding. Thirty-three TAP sequences were
      studied, and the patients' diaphragmatic motions were classified into four
      categories according to the distance their diaphragms moved. Results showed that
      the diaphragm was stationary in 33% of the TAP studies, while perpetual motion
      occurred in 15% of the studies, early-phase motion occurred in 12% and late-phase
      motion occurred in 40%. Ten sequences showed diaphragmatic motion of more than 10
      mm, with eight sequences showing caudal motion and two showing cranial motion.
      This article discusses the cause of diaphragmatic motion during breath-holding
      for hepatic angiography and presents suggestions to reduce motion artifacts
      during the exam.

PMID- 9253058
TI  - Reducing misregistration of mask image in hepatic DSA.
AB  - When performing hepatic digital subtraction angiography, misregistration of the
      mask image can cause artifacts that obscure pathology. For this article,
      researchers analyzed the breath expiration times of 59 patients and found that
      expiration times ranged from 1.8 seconds to 6 seconds. Thirty DSA series were
      obtained taking into account the patient's breath expiration time, and 35 series
      were obtained without taking the expiration time into consideration. Artifacts
      were detected in 20% of the DSA series where expiration time was taken into
      consideration and in 42.9% of series where it was not (p < 0.05). The research
      showed that misregistration of the mask image during hepatic DSA can be reduced
      by starting the exposure at the end of breath expiration.

PMID- 9253059
TI  - Radiographic imaging of small bowel disease.

PMID- 9253060
TI  - R.T. education, employment in Turkey.

PMID- 9253061
TI  - Living with rheumatoid arthritis.

PMID- 9253062
TI  - Imaging patients with chronic disabilities.
AB  - For some patients, a chronic disability occurs suddenly, such as when it is the
      result of an accident or a stroke. For others, the development of a disability is
      a gradual process, the result of a disease process such as multiple sclerosis or
      Alzheimer's disease. Regardless of whether a person becomes disabled slowly or
      gradually, a variety of psychological dynamics are involved. Because a loss has
      occurred, all disabled patients experience grief and go through denial,
      depression and the struggle for reintegration. It is essential that the radiology
      staff carefully assess each patient's feelings and encourage him or her to take
      control of life. Disabled people do not need to remain in the grieving stage
      forever. They can learn to adjust and adapt, and the radiologic technologist can
      help by providing support and encouragement. If the technologist knows what to
      expect and understands how to react, even the briefest encounter in the radiology
      department can have a positive effect on the patient's adjustment.

PMID- 9253063
TI  - Give students 'knowledge holes' to fill.

PMID- 9253065
TI  - Case of the season. Langerhans' cell histiocytosis with sclerosing cholangitis
      [SC] causing secondary biliary cirrhosis.

PMID- 9253064
TI  - Latex allergies can affect any of us.

PMID- 9253066
TI  - Cholangiography.

PMID- 9253067
TI  - Ultrasound of the bile ducts.

PMID- 9253068
TI  - Computed tomography of the bile ducts.
AB  - Although not typically a first-line test for patients with suspected biliary
      tract disease, improvements in CT technology have resulted in an increased
      ability for CT to detect and characterize causes of biliary obstruction and other
      biliary diseases. As with other abdominal neoplastic disease, CT is the most
      common imaging procedure for staging biliary tract malignancies. Attention to
      optimizing CT techniques and an awareness of subtle CT imaging findings can
      increase the efficacy of CT in evaluating the biliary tract.

PMID- 9253069
TI  - Magnetic resonance imaging of the bile ducts.

PMID- 9253070
TI  - The bile duct in liver transplantation.

PMID- 9253071
TI  - Congenital and acquired biliary disorders in children.

PMID- 9253072
TI  - Percutaneous interventions in the biliary tree.

PMID- 9253073
TI  - Left ventricular aneurysms: pathophysiologic observations and standard resection.
AB  - For the past four decades, the standard approach to the treatment of left
      ventricular aneurysms has been to resect the aneurysm wall and close it in a
      linear fashion. During the past decade, evidence has accumulated that this simple
      approach may not be the most efficacious in terms of either short-term
      ventricular function or long-term survival and quality of life. To establish the
      basis against which the newer techniques are to be compared, this article
      describe the historical evolution of procedures designed to treat ventricular
      aneurysms, the pathophysiolgy of aneurysms, the standard surgical technique still
      used by most surgeons, and the rationale for the newer surgical approaches.

PMID- 9253074
TI  - Left ventricular aneurysms: the endoventricular circular patch plasty.
AB  - The endoventricular circular patch plasty (EVCPP) technique was first used by us
      in 1984 to re-establish a more normal morphology of the left ventricular cavity
      distorted by post-myocardial infarction scar tissue. This technique includes the
      placement of a subendocardial circumferential pursestring suture inside the left
      ventricle around the base of the aneurysm at the junction of scarred and normal
      endocardium. A patch is then placed at this level to establish a new contour for
      the left ventricular cavity. Because this patch is placed at the junction of scar
      and normal endocardium, a substantial portion of the distal ventricular septum is
      excluded from the left ventricular cavity. The overall hospital mortality in our
      series of more than 715 cases is approximately 7% and, in the survivors, the
      ejection fraction is increased an average of 0.10.

PMID- 9253075
TI  - Surgical management of left ventricular aneurysms: a clarification of the
      similarities and differences between the Jatene and Dor techniques.
AB  - In the mid 1980s, two highly innovative and entirely new approaches to the
      surgical treatment of left ventricular aneurysms were introduced almost
      simultaneously and completely independently by Dr Adib Jatene in Sao Paulo,
      Brazil and Dr Vincent Dor, then at the University of Nice, France and now at the
      Centre Cardio-Thoracique de Monaco. The similarities between these two approaches
      to the repair of left ventricular aneurysms and their close temporal evolution
      have caused confusion regarding their differences and the precise surgical
      technique of each approach. It is the purpose of this article to clarify the
      similarities and differences between these two techniques.

PMID- 9253076
TI  - Reconstructive left ventricular surgery for post-ischemic akinetic dilatation.
AB  - The term dyskinesia refers to a post-ischemic fibrous area of ventricle that
      moves in a paradoxical manner during ventricular systole and diastole, ie, an
      aneurysm. Akinesia indicates that such an area of scarred ventricle exhibits no
      movement during either systole or diastole. In the past, it has been considered
      extremely important, from a surgical standpoint, to differentiate between
      dyskinesia, which can be treated surgically, and akinesia, which cannot be
      treated by surgery. Because the only alternative form of surgical therapy in many
      of these patients is cardiac transplantation, we have applied the technique of
      reconstruction of akinetic areas by our endocardial ventricular patch plasty
      technique in the same manner as that used for areas of dyskinesia. The surgical
      results, especially in patients with large areas of akinesia in the left
      ventricle, confirm the validity of this direct approach to the treatment of a
      frequently complex problem.

PMID- 9253077
TI  - The treatment of refractory ischemic ventricular tachycardia by endoventricular
      patch plasty reconstruction of the left ventricle.
AB  - Although the endoventricular patch plasty technique was originally developed to
      improve the functional status of the left ventricle following resection of an
      aneurysm, it became apparent early on in our experience that the technique also
      cured most cases of ventricular tachycardia associated with these aneurysms. As a
      result, we began to include as a part of our preoperative work-up an
      electrophysiology study in which we attempted to induce ventricular tachycardia
      even if it had not occurred spontaneously. Using our standard surgical approach,
      plus the use of cryotherapy, we have now operated on 106 patients with either
      spontaneous or inducible ventricular tachycardia preoperatively in association
      with ventricular dyskinesia or akinesia. The operative mortality in this series
      of patients was 7.5%. Postoperatively, ventricular tachycardia could not be
      induced in 92% of the survivors and only 2 patients have had episodes of
      spontaneous ventricular tachycardia. Because this technique does not require any
      intraoperative electrophysiological mapping, we believe this to be an excellent
      surgical approach for patients with refractory ischemic ventricular tachycardia.

PMID- 9253078
TI  - Current role of esophageal function studies.
AB  - The introduction of laparoscopic techniques for performing anti-reflux surgery
      has led to a significant increase in the number of such procedures being
      performed. Furthermore, the threshold of symptoms required for performance of
      such procedures seems to have been lowered. For these reasons, it is more
      important than ever to ensure that symptoms attributed to gastroesophageal reflux
      are appropriately evaluated for a high rate of clinical success after anti-reflux
      surgery. Clinical assessment requires a careful history, expert radiographic
      assessment, and endoscopy by an experienced observer. Objective measurements
      including esophageal manometry, acid perfusion studies, and 24-hour esophageal pH
      monitoring continue to play an important role in the diagnosis and management of
      associated functional disorders of the esophagus.

PMID- 9253079
TI  - Hiatus hernia and gastroesophageal reflux: indications for surgery and selection
      of operation.
AB  - It is generally agreed that no single surgical technique of repair provides
      adequate results under all circumstances. It is equally important to recognize
      that almost all conditions which complicate hiatus hernia and gastroesophageal
      reflux are of a benign order, and the decision for surgery is an option for the
      adequately informed patient. This article presents the indications for operation
      and the criteria for selection of open repairs. It is not a review article, but
      rather expresses the experience and opinions of the author.

PMID- 9253080
TI  - Current medical treatment and indications for surgical referral for
      gastroesophageal reflux disease (GERD).
AB  - Gastroesophageal reflux disease (GERD) is a common problem in medical practice.
      Estimates are that 10% of the U.S. population will experience daily heartburn and
      up to 40% will have symptomatic GERD on a frequent basis. Current medical therapy
      allows physicians to provide complete symptom relief, maintain long-term symptom
      remission and prevent complications. New advances in minimally invasive surgical
      techniques have made antireflux surgery an attractive alternate for long-term
      management in selected patients. This article reviews current medical treatment
      and indications for surgical referral in GERD.

PMID- 9253081
TI  - Laparoscopic antireflux surgery.
AB  - Laparoscopic antireflux surgery is a safe and effective alternative surgical
      approach for the treatment of gastroesophageal reflux disease (GERD). However,
      the same rigorous evaluation required for open fundoplication is mandated for
      patients undergoing laparoscopic antireflux surgery. For successful laparoscopic
      antireflux surgery, both the mastery of laparoscopic techniques and the
      application of the principles of antireflux surgery are required. Operative
      mortality and morbidity compare favorably with those of open antireflux
      procedures, and there is a marked reduction of certain complications. Meticulous
      laparoscopic technique during the mobilization of the gastric cardia and
      esophagus will limit mortality and intraoperative and postoperative
      complications. Although laparoscopic antireflux surgery shortens postoperative
      recovery and speeds return to work, it may be the double-edged sword causing
      early failures. Short and intermediate term results compare similarly with open
      antireflux surgery. Laparoscopic antireflux surgery is an important and
      significant advancement in the evolution of GERD therapy, its definitive role in
      the surgeon's armamentarium is dependent on evaluation of long-term data.

PMID- 9253082
TI  - An imager's guide to normal neck anatomy.
AB  - Neck anatomy is quite complex and presents a daily challenge to the head and neck
      radiologist. The goal of this article is to help the practicing radiologist
      understand the basic anatomy of the neck. The major emphasis of this article is
      on the neck spaces as delimited by the various layers of the deep cervical
      fascia. A discussion of neck surface anatomy is also included followed by a
      description of the major blood vessels, nerves, and lymphatics within the
      extracranial head and neck. The technical aspects of neck imaging are briefly
      mentioned, and normal CT and MRI images of the neck are provided. Finally, a few
      normal variants are illustrated.

PMID- 9253083
TI  - Non-nodal neck masses.
AB  - Planar imaging has made significant contributions to the evaluation of patients
      with non-nodal neck masses. The clinical history, physical examination, and
      imaging characteristics of these lesions are often complimentary. Yet, planar
      imaging much more accurately defines the size, location, and extent of these
      lesions than is revealed on physical examination. The CT and MR characteristics
      are often sufficiently specific to arrive at the correct preoperative diagnosis
      in these patients. We present the classical radiographic and clinical features of
      several non-nodal neck masses.

PMID- 9253084
TI  - Inflammatory and infectious lesions of the neck.
AB  - Diagnostic imaging is frequently used to evaluate the patient who has or may have
      an infection or other inflammatory lesion in the neck. In fact, these diagnoses
      and their differentiation from tumor may only be made after a careful
      radiological evaluation. This review will illustrate the imaging appearance of
      many of the common inflammatory conditions that may arise in the neck. In most,
      but not all cases, CT is the imaging study of choice in the initial work-up of
      this patient population.

PMID- 9253085
TI  - Imaging of cervical lymphadenopathy.
AB  - The identification and classification of cervical lymphadenopathy can be a
      challenging task for the general radiologist. Patients with a wide range of
      clinical presentation and disease states are often referred for imaging, although
      evaluation and staging of head and neck cancer is the most common indication. In
      addition to metastatic squamous carcinoma of the upper aerodigestive tract, the
      differential diagnosis of enlarged cervical lymph nodes includes the following:
      bacterial, mycobacterial and viral infections, granulomatous conditions such as
      sarcoidosis, primary and secondary involvement in lymphoma; other metastatic
      neoplasms such as from breast and lung, as well as more uncommon conditions such
      as sinus histiocytosis, eosinophilic granuloma, Kimura's disease, and Kikuchi's
      disease. This article will review the anatomy and regional classification of the
      cervical lymph node chains and discuss the common and uncommon etiologies of
      cervical lymph node enlargement.

PMID- 9253086
TI  - 1996 North American Spine Society presidential address.

PMID- 9253087
TI  - Anatomic relations of the thoracic pedicle to the adjacent neural structures.
AB  - STUDY DESIGN: This study analyzed anatomic parameters between the thoracic
      pedicles and the spinal nerve roots. OBJECTIVES: To quantitatively determine the
      anatomic relations of the thoracic pedicle to the adjacent neural structures.
      SUMMARY OF BACKGROUND DATA: Pedicular screw placement carries with it potential
      hazard to the surrounding neural structures, especially in the thoracic spine. No
      studies exist regarding the anatomic relations of the thoracic pedicle to the
      adjacent nerve roots. METHODS: Fifteen cadavers were obtained for study of the
      thoracic spine. All soft tissue was dissected off the thoracic spine. Laminectomy
      and total removal of the superior and inferior articular facets was then
      performed on C7-T1 through T12-L1 to expose the pedicles, nerve roots, and dura.
      Measurements were taken from the pedicle to the nerve root superiorly and
      inferiorly as well as between the pedicles. Also, the superoinferior diameter of
      the nerve root and the frontal angle of the nerve root were measured. Symmetrical
      structures were measured bilaterally. RESULTS: The results showed that no
      epidural space could be found between the dural sac and the pedicle in all 15
      cadavers. The average distances from the thoracic pedicle to the adjacent nerve
      roots superiorly or inferiorly at all levels ranged from 1.9 to 3.9 mm and from
      1.7 to 2.8 mm, with a minimum of 1.3 mm, respectively. The interpedicular
      distance increased from T1 (13.8 mm) to T3, slightly decreased in T4-T5, then
      gradually increased to T12 (16.6 mm). The superoinferior diameter of the nerve
      root increased consistently from 2.9 mm at T1 to 4.6 mm at T11. The frontal nerve
      root angle decreased consistently from T1 (120.1 degrees) to T12 (57.1 degrees),
      except at T4-T5. CONCLUSIONS: This study suggested that more care be taken into
      consideration in placing a transpedicular screw in the transverse plane than in
      placing a screw in the sagittal plane in the thoracic spine.

PMID- 9253089
TI  - Natural course of experimental scoliosis in pinealectomized chickens.
AB  - STUDY DESIGN: Pinealectomy induces experimental scoliosis in chickens. This study
      analyzed the natural course and characteristics of the scoliosis that developed
      after pinealectomy. OBJECTIVES: To investigate the natural course of experimental
      scoliosis after pinealectomy in chickens and determine its similarity to
      idiopathic scoliosis in humans. SUMMARY OF BACKGROUND DATA. Pinealectomy affects
      the systemic hormonal balance and consistently induces progressive scoliosis in
      chickens. METHODS: Thirty five chickens were divided into two groups, a
      pinealectomy group (n = 25) and a control group (n = 10). At the age of 3 days,
      all chickens in the pinealectomy group underwent surgery. Spinal radiographs of
      all chickens were taken at 2-week intervals until the age of 16 weeks. RESULTS:
      There was no alteration of spinal alignment in the control group. Seventeen
      chickens in the pinealectomy group had scoliosis (17 degrees-85 degrees) that
      featured a three-dimensional spinal deformity consisting of both lateral
      curvature and vertebral rotation with rib humps. The scoliosis progressed to
      become slight, moderate, or severe as the chickens grew older. Pinealectomized
      chickens showed several other differences from chickens of the normal control
      group, such as poor weight gain, underdeveloped cockscombs, and late onset of egg
      laying. CONCLUSIONS: The scoliosis developing in chickens after pinealectomy was
      similar to human idiopathic scoliosis, and thus seems to be a useful model of
      idiopathic scoliosis.

PMID- 9253088
TI  - The pathologic effects of intrathecal betamethasone.
AB  - STUDY DESIGN: The histopathologic effects of the intrathecal injection of
      betamethasone (Celestone Chronodose; Schering Corporation, Kenilworth, New
      Jersey) were assessed after the injection of various volumes of the preparation
      in 20 sheep. OBJECTIVE: To assess the safety of Celestone Chronodose injected
      into the intrathecal space. SUMMARY OF BACKGROUND DATA: The safety and efficacy
      of epidural steroid have received considerable attention in the medical
      literature in recent years. In Australia, reports of possible adverse effects of
      Depo-Medrol (methylprednisolone), including the complication of arachnoiditis,
      have been followed by statements from the manufacturers of commonly used steroid
      preparations recommending they should not be administered epidurally. Previous
      evidence suggests that arachnoiditis does not result from epidural administration
      of steroids, but may develop from the intrathecal administration of Depo-Medrol.
      There are no reports concerning the safety of Celestone Chronodose (beta
      methasone). METHODS: Twenty-three adult merino sheep had lumbar punctures
      performed at the L6-S1 level, and different volumes of Celestone Chronodose or
      normal saline were injected into the subarachnoid space. The animals were killed
      after 6 weeks, and the spinal cord, meninges, and nerve roots of the lumbar spine
      were examined for evidence of pathologic changes. RESULTS: There were no
      abnormalities demonstrated in three sheep injected with up to 18 ml of normal
      saline solution. Eleven sheep injected with 1 ml (5.7 mg) of Celestone Chronodose
      even when repeated at weekly intervals (five sheep, three injections) did not
      demonstrate pathologic changes. One of six sheep injected with 2 ml of Celestone
      Chronodose and all of three sheep injected with greater volumes showed
      histopathologic changes of arachnoiditis. CONCLUSIONS: Given that the volume of
      cerebrospinal fluid in the sheep is approximately one third of that in humans,
      this study suggests that small volumes (up to 2 ml) of Celestone Chronodose
      injected intrathecally in humans are unlikely to cause arachnoiditis, but that
      the risk of this complication increases substantially with higher doses.

PMID- 9253090
TI  - Mechanical stability of thoracolumbar pedicle screw fixation. The effect of
      crosslinks.
AB  - STUDY DESIGN: Pedicle screw fixation for unstable thoracolumbar spine injuries is
      relatively new. The effect of one or two crosslinks on rotational and lateral
      bending stiffness was studied. OBJECTIVE: To determine the rotational and bending
      stiffness values of thoracolumbar fractures fixed by the AO's internal fixation
      system with zero, one, or two crosslinks. METHODS: Eight embalmed thoracolumbar
      spine segments. (T12-L2) were instrumented at T12 and L2 with a pedicle screw-rod
      system. Rotational stiffness was determined for 10 cycles to 2.5 degrees, 3.5
      degrees, and 5 degrees of rotation, with and without one or two crosslinks, and
      lateral bending stiffness for 10 cycles to 0.25, 0.40, and 0.50 inch. The results
      showed a clear trend toward increased stiffness with crosslinks. RESULTS: The
      stiffness values of the two-crosslink construct at 2.5 degrees and 3.5 degrees of
      rotation were significantly higher than those of the zero-crosslink system. Also,
      the bending stiffness of the two-crosslink construct was significantly higher
      than that of no-crosslink system at all of the displacements. CONCLUSIONS:
      Rotational stiffness values of the two-crosslink construct were significantly
      higher than those of the zero-crosslink system, at 2.5 degrees and 3.5 degrees of
      rotation. Lateral bending stiffness of the two-crosslink system was higher than
      that of the zero-crosslink system at all levels of displacement.

PMID- 9253091
TI  - The success of anterior cervical arthrodesis adjacent to a previous fusion.
AB  - STUDY DESIGN: A retrospective review of all patients surgically treated for
      adjacent segment disease of the cervical spine over a 20-year period. OBJECTIVES:
      To determine the clinical and radiographic success of discectomy with interbody
      grafting and corpectomy with strut grafting in the treatment of adjacent segment
      disease of the cervical spine. SUMMARY OF BACKGROUND DATA: Up to 25% of all
      patients undergoing anterior cervical fusion have new disease due to degeneration
      of an adjacent segment within 10 years. The success of surgical treatment in
      these patients with adjacent segment disease has not been reported. METHODS:
      Thirty-eight patients were surgically treated for adjacent segment disease by
      discectomy with interbody grafting or corpectomy with strut grafting. Arthrodesis
      was evaluated by flexion-extension lateral radiographs and clinical outcomes were
      assessed using Robinson's criteria at least 2 years after surgery. Fusion rates
      were compared by Fisher's exact test, and outcomes were compared by rank-sum
      analysis. RESULTS: The rate of arthrodesis was significantly lower in the 24
      patients treated by discectomy with interbody grafting at one or more levels
      (63%) than in the 14 patients treated by corpectomy with strut grafting (100%; P
      = 0.01). Clinical outcomes were similar for the corpectomy and discectomy groups
      (P = 0.55). There was a trend toward better outcomes in patients who achieved a
      solid arthrodesis (P = 0.13). CONCLUSIONS: Achieving fusion is more difficult
      when anterior cervical arthrodesis is performed adjacent to a prior fusion. Strut
      grafting resulted in a significantly higher rate of arthrodesis than interbody
      grafting.

PMID- 9253092
TI  - Atlantoaxial fusion and retrodental pannus in rheumatoid arthritis.
AB  - STUDY DESIGN: This study analyzed the influence of atlantoaxial fusion in
      rheumatoid arthritis patients on inflammatory retrodental pannus. OBJECTIVES: To
      determine the value of fusion on the magnitude of pannus as a compressive
      structure on the spinal cord. SUMMARY OF BACKGROUND DATA: Transverse and vertical
      instability may lead to neurologic deficits from spinal cord compression.
      Increased size of the retrodental pannus can exacerbate the neurologic
      deterioration. Anterior removal of dens and pannus followed by posterior fusion
      has been proposed in such situations as a method to relieve spinal cord
      compression. METHODS: Twenty-two patients with atlantoaxial instability and
      verified pannus on magnetic resonance imaging underwent posterior fusion of the
      upper cervical spine. These patients were followed 12 to 75 months after surgery
      by clinical, radiologic, and magnetic resonance imaging evaluations. The size of
      the pannus was compared before and after surgery. RESULTS: In all patients, the
      retrodental pannus had significantly decreased or disappeared postoperatively.
      CONCLUSIONS: Pannus reduction occurred even in patients whose disease was active
      or progressing, supporting the hypothesis that the pannus is more a reactive
      fibrous tissue resulting from instability rather than a direct consequence of the
      inflammatory process itself.

PMID- 9253093
TI  - Anterior cervical pseudarthrosis. Natural history and treatment.
AB  - STUDY DESIGN: A retrospective study of long-term clinical outcomes in 48 patients
      with pseudarthroses after anterior cervical discectomy and fusion. OBJECTIVES: To
      determine the natural history, risk factors, and treatment outcomes in a large
      population with documented pseudarthrosis after anterior cervical discectomy and
      fusion. SUMMARY OF BACKGROUND DATA: Recent reports suggest that pseudarthrosis
      after anterior cervical discectomy and fusion adversely affects clinical outcome.
      Little data regarding cervical pseudarthroses have been published, and
      conclusions have been drawn from reports with small patient populations and short
      term follow-up periods. METHODS: Forty-eight patients with radiographically
      documented pseudarthrosis after anterior cervical discectomy and fusion were
      studied. Patients were examined and radiographs made at regular intervals (mean
      follow-up, 66 months). Clinical results were based on patients' assessment of
      pain, prescription drug use, activity level and Odom's criteria. Clinical
      outcomes in patients who underwent surgical repair of the pseudarthrosis are
      reported. RESULTS: Of the 48 patients, 32 (67%) with pseudarthroses were
      symptomatic at latest follow-up or at the time of further surgery. Of the 32
      patients, 9 had a symptom-free period of at least 2 years after the anterior
      cervical discectomy and fusion before redeveloping cervical symptoms after a
      traumatic episode. Of 48 patients with pseudarthroses, 16 (33%) remained
      asymptomatic at a mean of 5.1 years after anterior cervical discectomy and
      fusion. A younger age at the time of anterior cervical discectomy and fusion
      increased the likelihood of the pseudarthrosis becoming symptomatic. After
      multiple level anterior cervical discectomy and fusion, the caudal-most operated
      level accounted for 82% of the pseudarthroses. Sixteen patients had an anterior
      repair of the pseudarthrosis, and fusion was achieved in 14. Six patients
      underwent posterior pseudarthrosis repair, and all healed. In patients in whom
      fusion was achieved with a second cervical operation, the results were excellent
      in 19 and good in 1. CONCLUSION: A pseudarthrosis after anterior cervical
      discectomy and fusion is frequently associated with a poor clinical outcome.
      Surgical repair of the pseudarthrosis with an anterior or posterior approach
      seems to have a high likelihood of a successful clinical outcome.

PMID- 9253094
TI  - Vertebral column resection for the treatment of rigid coronal decompensation.
AB  - STUDY DESIGN: A retrospective study of patients with rigid coronal
      decompensation. OBJECTIVES: To determine if patients with rigid coronal
      decompensation can be safely and successfully treated by anterior-posterior
      vertebral column resection, spinal shortening, posterior instrumentation, and
      fusion to correct their deformities. SUMMARY OF BACKGROUND DATA: Previous
      investigators have described reconstructive techniques used to treat patients
      with sagittal and coronal spine deformities. These techniques include osteotomy
      and anterior or posterior fusion. Although a number of these studies consider the
      problems associated with failed back syndrome (flatback, coronal and axial
      imbalance, pseudarthrosis), they have not satisfactorily addressed the management
      of rigid coronal decompensation. The patient population of the current study, on
      average, presented with more severe, fixed deformities than those detailed in the
      literature, and required more extensive surgery than previously described.
      METHODS: Twenty-four patients (average age, 27 years) with rigid coronal
      decompensation underwent anterior-posterior vertebral column resection, spinal
      shortening, posterior instrumentation, and fusion. Degree of curvature was
      measured in the coronal and sagittal planes, and decompensation was assessed.
      Follow-up was from 2 to 10 years. RESULTS: Coronal and sagittal decompensation
      were corrected an average of 82% and 87%, respectively; T1 tilt and pelvic
      obliquity were improved by 65% and 53%, respectively; and scoliosis was improved
      by 52%. Complications occurred in 14 patients, but at follow-up all patients
      rated their results as either good or excellent. CONCLUSIONS: Patients with
      fixed, decompensated spinal deformity may be safely corrected by vertebrectomy,
      decancellation, spinal shortening, instrumentation, and fusion. Complications are
      transient, and the benefits in this select group of patients outweigh the risks.

PMID- 9253095
TI  - Degree of disc disruption and lower extremity pain.
AB  - STUDY DESIGN: Data were collected prospectively from patient-completed pain
      drawings, lumbar discographic pain responses, and computed tomographic
      discographic images. OBJECTIVES: To determine if there were differences in pain
      location or the type of pain associated with the severity of symptomatic disc
      disruption. SUMMARY OF BACKGROUND DATA: Lower extremity pain related to spinal
      pathology was for a long time attributed primarily to nerve root compression.
      However, this simple model could not explain all lower extremity pain. Other
      mechanisms such as biochemical agents have been implicated. Also, nerve endings
      have been found in the outer layers of the anulus. Such endings could be
      associated with pain referred from the disc into the lower extremities. Pain
      drawings have been used in several studies to investigate various back pain
      origins and provide an easily administered method to document pain location.
      METHODS: Pain drawings were completed by 187 patients undergoing discography at
      the three lowest levels. The study group consisted of 118 men and 69 women with
      an average age of 37.2 years (range, 18-62 years). Computed tomographic
      discograms were scored using the Dallas discogram description, which assigns
      separate scores for discs with disruption of outer anular fibers (Grade 2) and
      those with disruption of the outermost anular layers associated with deformation
      or herniation of the outer anular well (Grade 3). The pain response provoked with
      each disc injection was recorded as pressure only or painless, pain dissimilar to
      clinical symptoms, similar to symptoms, or the exact reproduction of clinical
      pain, in this study, the similar and exact reproduction responses were combined
      and considered to be "symptomatic." The drawings were classified based on the
      presence or absence of pain in three regions: low back or buttocks, thigh, and
      leg. The drawings were also scored using the system described by Ransford, and
      those that were likely to be indicative of psychological problems were analyzed
      separately (N = 43). RESULTS: There was no significant difference in the distal
      location of lower extremity pain among patients whose most severe symptomatic
      disc disruption was a Grade 2 compared with those with symptomatic Grade 3
      disruption (62.2% vs. 61.7%; P > 0.75; chi-square). The figure was similar for
      patients with both symptomatic Grade 2 and 3 disruption (72.7%). However,
      patients with symptomatic Grade 2 disruption used significantly more symbols to
      describe their pain, and in particular aching pain, than did those with
      symptomatic Grade 3 disruption. CONCLUSIONS: These results indicate that disc
      disruption passing into the outer layers of the anulus, but not resulting in
      deformation of the outer anular wall, was as frequently associated with lower
      extremity pain as were discs with more severe disruption deforming the outer
      anular wall; however, they were associated with a greater degree of aching pain.
      These findings support that lower extremity pain may be referred from the disc.

PMID- 9253096
TI  - Discography of lumbar discs after surgical treatment for disc herniation.
AB  - STUDY DESIGN: Eighty-three patients were identified who had discography performed
      at a disc level that had been subject to previous laminectomy and partial
      discectomy, and who had also undergone discography at one or more additional
      levels. The results of these studies were retrospectively reviewed. OBJECTIVE: To
      define the results of discography performed on previously operated discs. SUMMARY
      OF BACKGROUND DATA: It is not uncommon for the physician to encounter patients
      with complaints of persistent chronic back pain after surgical treatment of a
      lumbar disc herniation. Although such patients are frequently studied by
      discography, there is very little scientific literature to document the expected
      results. METHODS: A retrospective study of the results of discography on
      previously operated disc was performed. RESULTS: A positive pain response was
      significantly more likely in the previously operated discs than in the unoperated
      discs (P < 0.0001). Posterior extravasation of dye was noted in 34% (35 of 102)
      of the postoperative discs and 21% (29 of 136) of the unoperated discs. Positive
      concordant pain provocation was noted in 48 (75%) of the 64 discs showing
      posterior dye extravasation; 28 were postoperative discs and 20 were unoperated
      discs. CONCLUSIONS: Patients presenting with disabling back pain who had
      previously undergone surgical treatment for a herniated nucleus pulposus show a
      high (72%) incidence of concordant pain with discography of the previously
      operated level. Only 34% of the previously operated discs demonstrated posterior
      extravasation of discography dye. Persistence of a posterior anular defect was
      associated with a higher incidence of positive concordant pain response.

PMID- 9253097
TI  - Effect of exercise on sick leave due to low back pain. A randomized, comparative,
      long-term study.
AB  - STUDY DESIGN: The study was carried out as an open, randomized, multicenter,
      parallel-group study with an observation period of 12 months. Four norwegian
      physiotherapy institutes took part. Patients were subsequently followed for 12
      months of home exercise on their own, without for 12 months of home exercise on
      their own, without the supervision of a physiotherapist. OBJECTIVES: 1) To
      investigate and compare the effects of two different exercise programs on low
      back problems in patients after a 1-year training program under the supervision
      of a physiotherapist. 2) To investigate the effect supervision by, and motivation
      from, physiotherapists has on training compliance and efficacy. SUMMARY OF
      BACKGROUND DATA: After ordinary physiotherapy treatment for low back problems,
      patients were randomly allocated either to a conventional training program
      designed by physiotherapists or to a training program using a new Norwegian
      developed training apparatus called the TerapiMaster. The study included 153
      patients with low back problems, all of whom had been referred to physiotherapy
      by their general practitioners. One hundred twenty-six patients were followed for
      an additional 12 months when performing home exercise programs on their own.
      METHODS: Monitoring patient satisfaction with the training program, compliance
      with the program, and absenteeism from work during the training period. RESULTS:
      Patient satisfaction with both training programs was high, with about 83% of
      participating patients completing the study in accordance with the protocol. Mean
      absenteeism (SD) during the preceding year totaled 82.5 days (19.8) in the
      conventional training group and 61.6 days (14.7) in the TerapiMaster group.
      Significant reductions to 17.2 days (6.0) and 16.4 days (5.3) in the two groups,
      respectively, were recorded during the training period, corresponding to a 75% to
      80% reduction compared with the preceding 1-year period. Mean absenteeism showed
      a further significant decline during the 12-month period without supervised
      training. The average values were 9.9 days (3.2) for conventional training and
      9.3 days (3.1) for the TerapiMaster, respectively. CONCLUSIONS: Both exercise
      programs reduced absenteeism significantly (75-80%). No difference in the effects
      of the two different programs was discernible. Regular follow-up through
      encouragement and variation in the training programs appear to be important
      factors for motivating patients to adhere to regular exercise programs for low
      back problems. This thesis was corroborated by the 12-month study of unsupervised
      exercise.

PMID- 9253098
TI  - A prospective study of Waddell signs in patients with chronic low back pain. When
      they may not be predictive.
AB  - STUDY DESIGN: Analysis of the treatment-outcome predictive power of Waddell signs
      by evaluating them before and after functional restoration, with assessment of 1
      year socioeconomic outcomes. OBJECTIVE: To evaluate the presence of Waddell
      nonorganic signs in a group of patients with chronic low back pain presenting for
      functional restoration, and to determine whether they were predictive of
      treatment success of failure. SUMMARY OF BACKGROUND DATA: Waddell has described
      "nonorganic" physical signs in patients with chronic low back pain indicative of
      somatization. Other researchers have correlated high Waddell scores with
      psychosocial barriers that required additional consultation, and have suggested
      that diminution of a Waddell score during physical rehabilitation is predictive
      of subsequent therapeutic success. METHODS: Total positive Waddell signs score
      and individual sign scores were assessed at initial presentation for functional
      restoration treatment and at discharge in a group of 50 patients with chronic low
      back pain (average length of disability = 17.9 months; average age = 38.5 years).
      Patients were then tracked and assessed with a 1-year follow-up structured
      interview to evaluate outcome variables such as return to work, work retention,
      re-injury rate, health utilization, and subsequent surgery. RESULTS: Statistical
      analyses of these data revealed no significant associations between Waddell total
      positive score or changes in score and therapeutic success as measured by any of
      the behavioral outcomes such as return to work. Also, no predictive value was
      found for the individual positive signs of their changes and therapeutic success.
      CONCLUSIONS: Although positive Waddell signs have been found to be predictive in
      patients with short-term chronic low back pain, the current results suggest that,
      in patients who have longer duration of pain and who undergo a comprehensive
      functional restoration program, these signs are not significantly prognostic.
      Because functional restoration is an interdiscipilinary approach that effectively
      manages somatization complaints in a consistent manner by all treatment
      personnel, such complaints do not create any major barriers to recovery.
      Therefore, although Waddell signs may be predictive of treatment outcome in less
      intensive rehabilitation programs, they do not provide any predictive power in a
      comprehensive functional restoration program, which has a basic goal of managing
      barriers to recovery in a clinically efficacious manner.

PMID- 9253099
TI  - Objectification of functional improvement after nonoperative care.
AB  - STUDY DESIGN: In this article, the authors review the three broad categories of
      measures that have been used to objectify functional improvement after
      nonoperative care of painful spinal disorder patients-physical, psychological,
      and socioeconomic. For each of the three categories, the major measures used are
      discussed, as well as research relating to the efficacy of the measures.
      OBJECTIVE: To point out the many differences that still exist among research
      studies regarding which functional outcome measures to use and when to use them.
      SUMMARY OF BACKGROUND DATA: During the past few decades, it has been made
      abundantly clear that painful spinal disorders, particularly when associated with
      work disability and/or financial benefits, result from a complex interaction of
      medical, psychological, and social factors. This has resulted in frequent
      confusion regarding what constitutes the primary roots of the disabling process.
      Currently, a more comprehensive biopsychosocial perspective of chronic pain and
      disability has emerged that has significant implications for diagnostic and
      treatment philosophies of practitioners. METHODS: Identifying the measures
      frequently used to address the important biopsychosocial factors, and evaluating
      their relative benefits and drawbacks. RESULTS AND CONCLUSIONS: It is
      demonstrated that there has been an overall trend in recent years toward using
      more objective, quantifiable instruments, encompassing the physical,
      psychological, and socioeconomic parameters of outcomes research in painful
      spinal disorders. These changes will certainly improve the ability of researchers
      to tease out which factors tap more directly into such tissue as physical
      impairment, as well as create greater uniformity of measures that will permit
      direct comparisons between studies.

PMID- 9253100
TI  - Patient characteristics associated with diagnostic imaging evaluation of
      persistent low back problems.
AB  - STUDY DESIGN: Post hoc analysis of data from the National Low Back Pain Study, a
      prospective observational multicenter study of patients referred for the
      evaluation and treatment of persistent low back problems. OBJECTIVE: To identify
      patient characteristics associated with use of particular diagnostic imaging
      examinations in patients with persistent low back problems. SUMMARY OF BACKGROUND
      DATA: The Agency for Health Care Policy and Research clinical practice guidelines
      on low back problems suggest that the use of particular diagnostic imaging tests
      for a given patient should be based on specific characteristics of that patient.
      METHODS: Use of diagnostic imaging examinations in 2,374 patients with persistent
      low back problems who were enrolled in the National Low Back Pain Study from 1986
      to 1991 was analyzed. Stepwise logistic regression was used to identify patient
      characteristics that distinguish between enrollees who underwent particular
      imaging studies. RESULTS: Characteristics that distinguished patients who had
      undergone magnetic resonance imaging from those who had received only lumbo
      sacral spine radiographs included higher socioeconomic status, greater resource
      use in the preceding 12 months, more functional impairment, presence of sciatica,
      and presence of neurologic signs/symptoms suggestive of nerve root compromise.
      Suspected soft tissue involvement was characteristic of enrollees who had
      undergone magnetic resonance imaging, whereas suspected structural involvement
      characterized patients who received noncontrast computed tomography. Only
      nonclinical factors, such as higher annual household income, disability
      compensation, and male gender distinguished enrollees who had undergone both
      magnetic resonance imaging and computed tomography-myelography from those who
      received only computed tomography-myelography. CONCLUSION: Particular patient
      socioeconomic and clinical characteristics are associated with receipt of
      specific imaging studies in evaluation of persistent low back problems.

PMID- 9253101
TI  - Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year
      follow-up study in Framingham.
AB  - STUDY DESIGN: A 25-year follow-up study of 606 members of the population-based
      Framingham cohort, who had received lateral lumbar radiographs in 1967-1968 and
      1992-1993, and completed an interview on back symptoms at the second examination.
      OBJECTIVES: To evaluate whether calcific lesions in the posterior wall of the
      abdominal aorta, the source of the feeding arteries of the lumbar spine, are
      associated with disc degeneration or back pain, which would suggest that ischemia
      of the lumbar spine leads to disc degeneration. METHODS: The presence of
      radiographic aortic calcification was ascertained in front of each lumbar segment
      from L1 through L4, and disc degeneration at intervertebral spaces from L1-L2
      through L4-L5. The associations between aortic calcification, disc degeneration,
      and back pain were tested using logistic regression with adjustment for age and
      sex. RESULTS: At the baseline examination, aortic calcification was significantly
      associated with general disc degeneration, that is, disc space narrowing or
      endplate sclerosis at any lumbar level (odds ratio 1.6; 95% confidence interval
      1.0-2.5; P = 0.034). In longitudinal, level-specific analyses, comparing local
      aortic calcifications with disc degeneration at the matching level, aortic
      calcifications predicted disc deterioration, that is, a decrease in disc space or
      appearance of endplate sclerosis, between the examinations (odds ratio 1.5; 95%
      confidence interval 1.3-1.8; P < 0.001). Furthermore, subjects in whom aortic
      calcifications developed between the examinations had disc deterioration twice as
      frequently as those in whom aortic calcifications did not develop (odds ratio
      2.0; 96% confidence interval 1.2-3.5; P = 0.013). Also, individuals with severe
      (Grade 3) posterior aortic calcification in front of any lumbar segment were more
      likely than others to report back pain during adult life (odds ratio 1.6; 95%
      confidence interval 1.1-2.2; P = 0.014). CONCLUSIONS: Advanced aortic
      atherosclerosis, presenting as calcific deposits in the posterior wall of the
      aorta, increases a person's risk for development of disc degeneration and is
      associated with the occurrence of back pain.

PMID- 9253102
TI  - A prospective analysis of magnetic resonance imaging findings in patients with
      sciatica and lumbar disc herniation. Correlation of outcomes with disc fragment
      and canal morphology.
AB  - STUDY DESIGN: A two-part observational study. In Part 1, consecutive lumbar
      magnetic resonance imaging scans in patients with sciatica meeting enrollment
      criteria were prospectively and blindly analyzed by a set protocol. In Part 2,
      further clinical findings at the time of the magnetic resonance imaging were
      obtained by retrospective chart review and outcome assessment done at follow-up
      of more than 2 years. OBJECTIVES: To determine the quantitative magnetic
      resonance findings of disc and canal measures in patients with sciatica and to
      analyze the predictive values of these magnetic resonance imaging and clinical
      variables on outcomes. METHODS: Part 1: Consecutive patients with a primary
      diagnosis of sciatica who came to lumbar magnetic resonance imaging were
      enrolled, and magnetic resonance imaging dimensions of discs and canal at the
      herniated level were collected. Part 2: Of 186 patients in Part 1, 135 were
      followed for more than 2 years; 87 were treated conservatively, and 48 were
      treated surgically. Outcomes were judged on satisfaction, activity level,
      medication intake, and reported pain at follow-up (mean, 2.6 years). RESULTS:
      Part 1: Wide ranges of disc and canal measurements were seen in all parameters.
      Significant differences in all magnetic resonance parameters were noted between
      male and female patients. Men had proportionately greater canal compromise by the
      affected disc than women. Positive sciatic tension signs and short duration of
      symptoms correlated with large disc herniation. Right-sided symptomatic
      herniations were usually larger than left. Part 2: At follow-up, predictors of
      outcome were determined independently for the surgery and the nonoperative
      groups. In the nonoperative group, a shorter duration of sciatica was the most
      significant predictor of a good outcome (P = 0.0018). Moreover, a duration of
      symptoms less than 6 months, no involvement with litigation, and younger age were
      also correlated with a favorable outcome. The only magnetic resonance parameter
      associated with good outcome was a small ratio of disc hemiarea to remaining
      canal hemiarea (P = 0.045). For the surgical group, a larger anteroposterior disc
      length was the most significant independent predictor of a positive outcome (P <
      0.0001). Larger ratios of disc area to canal area are also significantly
      associated with good outcomes (P < 0.0001), as are large disc areas and small
      remaining canal areas. Large right-left canal widths and small disc widths are
      also identified as predictors of a favorable outcome. Of the clinical parameters,
      concurrent medical illness, workers' compensation involvement, and female gender
      appear to be the most significantly correlated with poor outcome. All fair or
      poor surgical outcomes were in patients with smaller (< 6 mm) disc herniations.
      CONCLUSIONS: Quantitative measurements by magnetic resonance imaging of disc and
      canal morphology of 188 patients with sciatica indicate a wide range of
      herniation and canal sizes, with significant differences between men and women.
      In a cohort of 135 patients followed for more than 2 years, demographic and
      clinical features appeared to predict outcomes of nonoperative treatment, whereas
      morphometric features of disc herniation and the spinal canal seen on magnetic
      resonance imaging were much more powerful predictors of surgical outcomes.

PMID- 9253103
TI  - The sagittal pelvic tilt index as a criterion in the evaluation of
      spondylolisthesis. Preliminary observations.
AB  - STUDY DESIGN: Radiographic analysis of a pediatric population with
      spondylolisthesis was performed to examine sagittal plane pelvic rotation and
      degree of slip over time. OBJECTIVES: To determine whether the degree of standing
      sagittal offset of L5 with respect to the acetabulum correlated with slip
      progression and symptoms. SUMMARY OF BACKGROUND DATA: The natural history of
      isthmic spondylolisthesis remains unclear. Attempts to predict slip progression
      in the clinical setting, and thus the possible need for eventual surgical
      intervention, remain imprecise. Predicting slip progression based on sagittal
      alignment of the L5 vertebra with respect to the acetabulum has been proposed by
      some investigators. METHODS: Fifty-two children and adolescents were followed
      clinically and radiographically for an average of 5.6 years. Serial lateral
      standing radiographs that included the hips and lumbar spine were measured to
      compute a sagittal pelvic tilt index. The latter value is a ratio of relative
      distances from the center of S2 to the projection of L5 and the center of the
      femoral heads on the horizontal. RESULTS: Of the 52 patients studied, 38 have
      remained asymptomatic without significant slip progression or change in sagittal
      pelvic tilt index ratio. Of the original group, 13 patients had significant
      symptoms and revealed a decrease in the sagittal pelvic tilt index over time.
      Eight of the 13 stabilized at the end of adolescence, whereas 5 had continued
      decrease in the sagittal pelvic tilt index ratio. These five required operative
      treatment for pain and progressive slip. CONCLUSIONS: The sagittal pelvic tilt
      index gives the examiner an objective measure of the stability of the lumbosacral
      junction by quantifying the relationship between S2, the center of the hip, and
      L5. A decreasing sagittal pelvic tilt index ratio in this preliminary series
      correlated with slip progression and risk of conservative treatment failure,
      whereas those patients with a stable sagittal pelvic tilt index did not progress
      and remained clinically asymptomatic.

PMID- 9253104
TI  - Delayed postoperative paraparesis in scoliosis surgery. A case report.
AB  - STUDY DESIGN: A case report is presented of an unusual complication of scoliosis
      surgery that, to the authors' knowledge, has never been reported in the
      literature. OBJECTIVE: Neurologic complications can occur after an uneventful
      posterior spinal instrumentation and fusion for scoliosis. Careful observation
      during the post-operative period is crucial for early detection of impending
      neurologic deficit. SUMMARY OF BACKGROUND DATA: Nerve compression of the cauda
      equina has been reported as a complication of different types of surgery in the
      lumbar spine, but an ascending paraparesis has never been described as a
      complication of scoliosis surgery. METHODS: A 12-year-old boy with a right
      thoracic scoliosis measuring 68 degrees and a 72 degrees left lumbar curve
      underwent Cotrel-Dubousset instrumentation and fusion from T5 to L4. Spinal cord
      monitoring with somatosensory evoked potentials and motor action potential were
      recorded and stable through out the entire procedure. Thirty hours later, a
      rapidly progressive ascending para-paresis developed that required urgent
      decompression. RESULTS: This patient underwent urgent decompression and removal
      of the Cotrel-Dubousset instrumentation. After surgery, the clinical picture
      improved gradually, and at 2-month follow-up he had regained normal strength in
      his lower limbs except for a grade 4 left extensor hallucis longus. By 4 months
      postdecompression, he had made a total recovery. CONCLUSIONS: Although clinical
      examination may be difficult to perform in patients who are unconscious, on large
      doses of narcotic drugs, or mentally retarded, careful observation during the
      postoperative period and awareness of this complication can allow early detection
      of impending reversible neurologic deficit and provision of appropriate
      treatment.

PMID- 9253105
TI  - Sacroiliac joint pain.

PMID- 9253106
TI  - Neck and shoulder pain after laminoplasty.

PMID- 9253107
TI  - Risk of manipulative cervical treatment.

PMID- 9253108
TI  - Mechanisms of the graft-versus-leukemia reaction.
AB  - It is now clear that the graft-versus-leukemia (GVL) effect which accompanies
      allogeneic bone marrow transplantation for hematological malignancies is a
      powerful therapeutic weapon which, if harnessed, could improve our ability to
      treat refractory malignant disorders. Advances in the understanding of the
      alloimmune response now provide a clearer picture of the mechanisms involved in
      the GVL reaction: the CD4+ T cell plays a central role in the orchestration of
      leukemia cell killing. The immunogenicity of the leukemia is also a major factor
      determining the effectiveness of the GVL response. The characterization of
      antigens restricted to leukemia and hematopoietic tissues should make it
      eventually possible to produce specific and powerful antileukemic alloresponses
      in donor lymphocytes by adoptive immunotherapy or by vaccines.

PMID- 9253109
TI  - Signaling mechanisms in growth factor-stimulated cell motility.
AB  - Most mammalian cells have the capacity to migrate. When placed into culture,
      cells will generally display a set rate of basal, unstimulated locomotion. The
      cells will begin to move in one direction and, after some time, change directions
      resulting in a random walk. External stimuli can influence cell motility in
      several ways to either enhance or retard the rate of migration (chemokinesis), to
      change the average amount of cell migration observed before the cell turns
      (persistence), or to increase the directionality of movement by limiting the
      number of turns made by the cells. Several factors have been identified that
      stimulate cell movement, but the signaling mechanisms that mediate this induced
      cell movement have only recently begun to be studied. In this review, we discuss
      the signals that support the directional movement of fibroblasts and epithelial
      cells in response to chemoattractant gradients. The work will emphasize studies
      carried out by our laboratory and others on the stimulation of cell motility by
      the PDGF. These results indicate that at least two sets of signaling molecules
      cooperate to regulate cell motility in vivo. These include phospholipase C-gamma,
      phosphoinositide-3' kinase and the Ras-GTPase activating protein Ras-GAP. The
      first set are those which bind to the intracellular domain of the receptor
      tyrosine kinase and bring about the phosphorylation and/or activation of
      intracellular effectors proximal to the receptor. The second is a set of down
      stream effectors that regulate either the rate of cell movement or the
      directionality of that movement depending on the cell type. These include Ras and
      the Ras-related GTPase Rac along with free phosphoinositides and calcium ions
      that regulate the actin polymerization machinery. Signals that mediate nuclear
      changes leading to cell proliferation, such as elements of the MAP kinase
      pathway, do not appear to play a role in PDGF-stimulated cell migration. Current
      work thus suggests that a coordinated spatial regulation of signaling elements
      that interact with the cell membrane and cytoskeleton but not necessarily with
      nuclear elements is the controlling mediator of directional cell motility.

PMID- 9253110
TI  - In vitro proliferation and differentiation of erythroid progenitors of cord
      blood.
AB  - Stem cell factor (SCF) is known to synergize with erythropoietin (EPO) for
      erythropoiesis in vitro. Clonogenic assay and suspension culture were used to
      assess the effect of EPO alone or its combination with SCF on the proliferation
      and differentiation of erythroid progenitors of cord blood. Colony formation,
      increase in cell count, and cell cycling status for the proliferation as well as
      expression of Glycophorin A (Gly A) and hemoglobinization as the marker of
      differentiation were determined with each stimulation. The cell cycle status of
      the cells in suspension cultures was determined using FACScan after labeling of
      cells with propidium iodide. Expression of Gly A and degree of hemoglobinization
      were determined by FACScan and spectrophotometer on the cells plucked from
      colonies in semisolid culture. Larger increases in cell counts in suspension
      culture were observed with EPO + SCF after 12 days of inoculation than with EPO
      alone. Mean doubling time was 14.2 h with EPO + SCF and 22.7 h with EPO alone.
      The proportion of cells in S and G2 + M phase in day 14 suspension culture was
      48% with EPO + SCF and 43% with EPO alone (no significant difference). Mean
      colony counts per 10(5) nonadherent mononuclear cells were 76 +/- 14 with EPO +
      SCF and 51 +/- 15 with EPO at day 14 (p < 0.05). The number of macroscopic
      colonies with > 0.5 mm diameter was 10.7 +/- 1.2 with EPO + SCF and 0.3 +/- 0.5
      with EPO (p < 0.05). Percent of Gly A+ cells was 75% for both EPO + SCF and EPO
      colonies at day 14. Hemoglobin concentration/10(5) cells at day 14 was 0.70 +/-
      0.17 microgram with EPO + SCF, and 1.16 +/- 0.32 micrograms with EPO alone (p <
      0.05). In conclusion, SCF in the combination with EPO showed a synergistic effect
      for erythroid proliferation in colony number as well as colony size derived from
      cord blood, while SCF with EPO decreased hemoglobin synthesis but not Gly A
      expression at day 14.

PMID- 9253111
TI  - Coexpression of Kit and the receptors for erythropoietin, interleukin 6 and GM
      CSF on hemopoietic cells.
AB  - The detection of functional growth factor (GF) receptors on subpopulations of
      hemopoietic cells may provide a further dissection of immature cell subsets.
      Since little information is available about coexpression of different GF
      receptors at the level of single hemopoietic cells, we studied the feasibility of
      simultaneous cell staining with a combination of biotin- and digoxigenin-labeled
      GFs for flow cytometric detection of functional receptors. Using this
      methodology, coexpression of Kit and receptors for erythropoietin (EPO),
      interleukin 6 (IL-6), and GM-CSF on hemopoietic cells was studied by triple
      staining of rhesus monkey bone marrow (BM) cells with labeled GFs and antibodies
      against other cell surface markers. Most of the immature, CD34+2 cells were Kit+
      but did not display detectable levels of EPO-receptors (EPO-Rs) or GM-CSF-R.
      Approximately 60% of these CD34+2/Kit+ cells coexpressed the IL-6-R,
      demonstrating that immature cells are heterogeneous with respect to IL-6-R
      expression. Maturation of monomyeloid progenitors, as demonstrated by decreasing
      CD34 and increasing CD11b expression, is accompanied by a decline of Kit and an
      increase in GM-CSF-R expression in such a way that Kit+/GM-CSF-R+ cells are
      hardly detectable. IL-6-R expression is maintained or even increased during
      monomyeloid differentiation. IL-6-R and GM-CSF-R were not identified on most
      CD71+2 cells, which indicated that these receptors are probably not expressed
      during erythroid differentiation. Together with previous results, our data show
      that both Kit and CD71 are upregulated with erythroid commitment of immature
      progenitors. Upon further differentiation, Kit+/EPO-R-cells lose CD34 and acquire
      EPO-R. Maturing erythroid cells eventually lose CD71 and Kit expression but
      retain the EPO-R. In conclusion, this approach enables further characterization
      of the specificity of GFs for different bone marrow subpopulations. Apart from
      insight into the differentiation stages on which individual GFs may act,
      information about receptor coexpression may be used to identify individual cells
      that can respond to multiple GFs, and allows for further characterization of the
      regulation of lineage-specific differentiation.

PMID- 9253112
TI  - Differential effect of erythropoietin and GM-CSF on megakaryocytopoiesis from
      primitive bone marrow cells in serum-free conditions.
AB  - In this study we have explored the effect of recombinant human erythropoietin
      (EPO) and recombinant murine GM-CSF on megakaryocyte progenitors (colony forming
      units-megakaryocyte [CFU-Mk]) using a serum-free fibrin clot assay and enriched
      primitive hematopoietic progenitors of marrow cells from day 4 post-5
      fluorouracil-treated mice. We have monitored the production of high proliferative
      potential-colony forming cells ([HPP-CFC]; compact colonies, > 0.5 mm) and
      studied their relationship to CFU-Mk formation. EPO induced the formation of
      small numbers of megakaryocyte colonies, but acted together with the
      megakaryocyte-stimulating factors, stem cell factor (SCF) and interleukin (IL-3),
      to augment the size of CFU-Mk (colonies with > 50 megakaryocytes/colony). A
      strong correlation between the number of CFU-Mk and HPP-CFC formation from 5
      fluorouracil bone marrow cells was observed when these cells were stimulated with
      EPO in the presence of SCF and IL-3. On the other hand, GM-CSF alone had no
      effect on megakaryocyte colony formation. Moreover, GM-CSF in the presence of SCF
      and IL-3 potentiates the HPP-CFC formation (i.e., an increase of 3.1-fold
      compared to the effect induced by SCF+IL-3) with strong inhibitory effects on the
      number and size of megakaryocyte colonies. Although several studies suggest that
      EPO and GM-CSF can stimulate megakaryocytopoiesis, our results indicate that
      neither EPO nor GM-CSF alone are sufficient to stimulate primitive progenitors
      committed to the megakaryocyte lineage. The fact that EPO can exert a strong
      effect on the size of CFU-Mk induced by SCF/IL-3 suggests that only those
      megakaryocyte progenitors previously stimulated by other megakaryocyte
      stimulating factors are able to respond to EPO. These findings may explain the
      physiological and clinical observations in which high levels of EPO are often
      associated with thrombocytosis.

PMID- 9253113
TI  - Serum ferritin iron, a new test, measures human body iron stores unconfounded by
      inflammation.
AB  - Serum ferritin protein is an acute phase reactant. We hypothesized that serum
      ferritin protein generated in response to an inflammatory process would have much
      less iron (Fe) in it than would "normal" ferritin protein, and therefore
      measuring serum ferritin iron would assess human body iron status unconfounded by
      inflammation. BASIC METHODS: We measured serum ferritin iron in 140 clinical
      samples obtained from the serum banks of Bronx VA Medical Center Hematology and
      Nutrition Laboratory (Bronx, NY), the CDC Nutritional Biochemistry serum sample
      bank (Atlanta, GA), and the sample bank from patients with thalassemia and iron
      overload treated at New York Hospital (New York, NY). Each was analyzed for three
      conventional criteria of iron status: serum iron, percentage of transferrin
      saturation and ferritin protein. In addition, tests for inflammation were also
      performed: C-reactive protein, WBC and transaminases. Seventy-seven patients'
      sera from 140 screened met each of three consistent criteria for stages of iron
      status. Serum ferritin was immobilized by immunoprecipitation with rabbit
      antihuman polyclonal antibody bound to agarose and separated from other iron
      containing proteins, digested with 0.2 ml of 3N nitric acid and analyzed for iron
      content by atomic absorption spectroscopy. RESULTS: Serum ferritin iron ranged in
      normal controls from 10 ng to 35 ng Fe/ml. The patients with iron deficiency
      (4/4) and those in negative iron balance (5/6) had values < or = 10 ng. Positive
      iron balance (8/9) and iron overload (22/22) values were > 35 ng/ml, in contrast
      to 11/19 with inflammation. Seventeen of twenty-two with overload had values >
      100 ng/ml while only 1/19 with inflammation had such a value. Ferritin iron in
      ferritin protein was > 15% by weight in 14/22 with iron overload but in 0/19 with
      inflammation. IMPLICATIONS OF THE WORK: Serum ferritin iron is a simple, direct
      measure of iron stores that we propose, in conjunction with measuring serum
      ferritin protein, as a minimally invasive screening procedure for accurately
      assessing the whole range of human body iron status, unconfounded by
      inflammation.

PMID- 9253114
TI  - Purging peripheral blood progenitor cell grafts from lymphoma cells: quantitative
      comparison of immunomagnetic CD34+ selection systems.
AB  - Autologous peripheral blood progenitor cell (PBPC) transplantation is
      increasingly being used for treatment of indolent lymphomas. Since involvement of
      bone marrow and peripheral blood is frequent and methods to reduce the lymphoma
      cell load of PBPC grafts are thus highly desirable, we have studied purging of
      PBPC comparing two immunomagnetic CD34+ selection systems (VarioMACS, Miltenyi
      Biotech; Bergisch Gladbach, Germany, and Isolex50 System, Baxter; Irvine, CA).
      Samples of freshly collected mobilized PBPCs were contaminated with BALM-3 or
      KARPAS422 lymphoma cells that had been labeled with the fluorescent DNA stain
      Hoechst 33342. The mixture was subjected to separation with the two devices and
      the resulting "CD34+" fractions were screened for lymphoma cells by limiting
      dilution using fluorescence microscopy and by polymerase chain reaction
      amplification of t(14;18) or CDRIII-rearrangements. Both devices yielded
      comparable purities (MACS 97% [87%-99%]; Isolex 97% [84%-99%]) and recoveries of
      CD34+ cells (MACS 56% [30%-81%]; Isolex 45% [24%-63%]). The overall depletion of
      lymphoma cells was 3.9 log (2.6-5.9), however, residual contaminating cells were
      seen in every single experiment. The purging efficacy was dependent on the type
      of contaminating lymphoma cell (BALM-3: 4.4 log [3.7-4.8]; KARPAS422: 3.2 log
      [2.6-4.2]; p = 0.018), whereas the type of selection system used or the
      percentage of CD34+ cells in the starting material had no influence. We conclude
      that excellent purification of CD34+ cells leading to a vigorous depletion of
      lymphoma cells can be achieved with both CD34+ selection systems investigated.
      However, the efficacy of purging may greatly differ between individual lymphomas,
      and complete eradication of contaminating cells from PBPC grafts may rarely be
      achieved with CD34+ selection alone.

PMID- 9253115
TI  - Importance of parenchymal:stromal cell ratio for the ex vivo reconstitution of
      human hematopoiesis.
AB  - Many new developments in tissue engineering rely on the culture of primary
      tissues which is composed of parenchymal and mesenchymal (stromal) cell
      populations. Because stroma regulates parenchymal function, the
      parenchymal:stromal cell (P:S) ratio will likely influence culture behavior. To
      investigate parenchymal-stromal cell interactions, the P:S ratio was
      systematically varied in a human bone marrow (BM) culture system, measuring the
      output of mature cells, immature progenitors (colony forming units
      granulocyte/macrophage [CFU-GM]), and primitive stem cells (long-term culture
      initiating cells [LTC-IC]). When parenchymal CD34-enriched cells were grown
      without stroma, cell and CFU-GM output increased linearly as inoculum density was
      increased, resulting in constant cell and CFU-GM expansion ratios. On irradiated
      preformed stroma (IPFS), culture output was significantly higher and less
      dependent on CD34-enriched cell inoculum density, resulting in greater expansion
      ratios at lower inoculum densities. The number of IPFS cells required to support
      CD34-enriched cells was independent of the CD34-enriched cell number, suggesting
      that IPFS did not provide discrete niches, but instead acted through soluble
      signals. Experiments using conditioned medium (CM) from IPFS confirmed the
      presence of soluble signals, but CM did not completely substitute for direct
      contact between CD34-enriched cells and IPFS. Because of known differences
      between IPFS and stroma growing within BM mononuclear cell (MNC) cultures,
      experiments were next performed using mixtures of CD34-enriched and CD34-depleted
      fractions of MNC. When inoculated with a fixed CD34+lin- cell number, culture
      output was optimal near the P:S ratio of the unmanipulated MNC sample and
      declined as CD34- cell number was increased or decreased. In cultures inoculated
      with a fixed total cell number, CFU-GM output increased as CD34+lin- cell number
      was increased, whereas LTC-IC output reached a plateau. These data suggest that a
      limited number of LTC-IC supportive niches were present in MNC stroma, whereas
      IPFS lacks these niches and acts predominantly through a less potent soluble
      mechanism. These studies underscore the importance of parenchymal-stromal cell
      interactions in the ex vivo reconstitution of tissue function and offer insight
      into the nature of these interactions in the human BM culture system.

PMID- 9253117
TI  - Immunohistochemical determination of p53 protein in prostatic cancer and
      prostatic intraepithelial neoplasms.
AB  - A role of genetic alterations in the p53 tumor suppressor gene has been
      implicated in many types of human malignancies. In this study, we examined the
      prevalence of immunohistochemically detectable p53 accumulation in prostatic
      tissues obtained from patients with prostatic adenocarcinoma, benign prostate
      hyperplasia and prostatic intraepithelial neoplasms. Six of 36 (16.7%) cancer
      cases and 2 of 11 (18.2%) cases of high-grade prostatic intraepithelial neoplasms
      showed p53 expression while no nuclear staining was observed in normal and
      hyperplastic prostatic tissues. Correlation of p53 expression with cancer stage,
      Gleason score and serum prostate-specific antigen level demonstrated that there
      was no statistically significant relationship between p53 expression and these
      clinicopathological parameters. Also, no significant association between p53
      expression and prognosis was observed.

PMID- 9253116
TI  - Growth of human hematopoietic cells in immunodeficient mice conditioned with
      cyclophosphamide and busulfan.
AB  - Human hematopoietic cells survive and proliferate for at least 10 weeks in severe
      combined immunodeficient mice prepared with the cytotoxic drugs busulfan and
      cyclophosphamide. The human cells growing in the mice can be detected by in situ
      hybridization using a probe detecting human repetitive DNA or by staining the
      cells with antihuman antibodies (anti-CD45 and anti-HLA I).
      Busulfan/cyclophosphamide-treated mice were injected with a wide range of cell
      doses, ranging from 5 to 50 million unfractionated bone marrow cells and 2 to 40
      million low density bone marrow cells. Animals were killed at 1, 3, 5, 7 and 10
      weeks after transplantation. Human cells were found in many animals and could be
      detected as early as one week after transplantation. The peak of repopulation was
      at two to five weeks, but in some animals human cells could be detected for as
      long as 10 weeks. Many of the human cells expressed high levels of glycophorin,
      but mature human erythrocytes were not found. The human cells were not uniformly
      distributed throughout the marrow. They grew in small clusters in the
      subepiphyseal region. The extent of human hematopoietic repopulation in the mouse
      was extremely variable. At no time and at no dose was repopulation achieved in
      all of the animals. Treatment with human growth factors is not necessary for the
      survival of the human hematopoietic cells but, in their absence, normal
      hematopoiesis does not occur.

PMID- 9253118
TI  - Chromophobe cell renal carcinoma: DNA flow cytometry and proliferation status in
      9 cases.
AB  - Nine cases of chromophobe cell renal carcinoma are reported, 2 in pregnant women.
      One neoplasm progressed and the patient died of disease, and this tumor presented
      the highest mitotic index and focal positivity to Ki-67 antibody. DNA flow
      cytometric study discovered 89% of aneuploidy, with 3 tetraploid cases. We
      conclude that chromophobe cell renal carcinoma is a relatively indolent but
      clearly malignant neoplasm. We suggest that the mitotic index could be the best
      method to predict malignant behavior. The high incidence of aneuploid cell lines
      may be due to structural anomalies; it is not indicative of malignant behavior.

PMID- 9253119
TI  - Influence of experimental spermatic cord torsion on the contralateral testis in
      rats. Evaluation of tissue free oxygen radical scavenger enzyme levels.
AB  - To evaluate the degree of ischemia formation in the contralateral testicle
      following unilateral testicular torsion, free oxygen radical formation after
      detorsion or an orchiectomy procedure in terms of superoxide dismutase (SOD) and
      catalase activities was detected in adult male Wistar rats. Animals were divided
      into 4 groups and following 2 and 6 h of unilateral torsion, the orchiectomy or
      detorsion procedures were performed and free radical scavenger enzyme activities
      (SOD, catalase) were measured in the contralateral testes after 24 h, 1 week and
      1 month. Evaluation of our results revealed no meaningful ischemia formation in
      the contralateral testes of rats undergoing 2 h of unilateral testicular torsion.
      However, animals undergoing 6 h of unilateral testicular torsion demonstrated a
      statistically significant alteration with respect to enzyme concentrations.
      Alterations in the contralateral testes were more prominent in animals that had
      undergone the detorsion procedure following 6 h of testicular torsion. Our
      results indicate that preservation of twisted testes through a detorsion
      procedure could cause further deterioration by way of reperfusion injury,
      indicating the importance of removal of the damaged testicle to minimize long
      term histopathologic alterations in the contralateral testes.

PMID- 9253120
TI  - Safety and efficiency of laparoscopic varicocelectomy in one hundred consecutive
      cases.
AB  - The purpose of this study is to report the safety and efficiency of laparoscopic
      varicocelectomy in 100 consecutive patients operated at a single teaching
      institution. There were three indications: (1) infertility associated with oligo
      astheno-teratospermia (n = 52); (2) chronic dragging sensation of the left
      testicle (n = 42), and (3) incidental finding of a large varicocele in young
      adolescents (n = 6). In group 1, the postoperative pregnancy rate was 47% and
      sperm quantity, concentration and mobility were significantly increased. The
      efficiency in pain control and clinical outcome amounted to 80 and 100% in groups
      2 and 3, respectively. Complications were few and minor. There was no
      intraperitoneal organ or major vessel injury. The mean length of hospital stay
      (0.9 days) and median total recovery time (5 days) were remarkably short. In
      conclusion, laparoscopic varicocelectomy is a safe procedure. It is as efficient
      as open spermatic vein ligation, and provides the patient with a short hospital
      stay and quick full recovery.

PMID- 9253121
TI  - Two-plane modified radical retropubic prostatectomy.
AB  - Salvage radical prostatectomy may be effective in patients refractory to
      radiation therapy. We describe a modified technique of radical retropubic
      prostatectomy, whereby a transverse incision in the cul-de-sac is made and the
      seminal vesicles and vas deferens are dissected away from the posterior surface
      of the bladder. This plane which follows the anterior layer of Denonvilliers'
      fascia is carried up to the bladder neck. The second plane of dissection follows
      the posterior layer of Denonvilliers' fascia up to the apex of the prostate. The
      peritoneal incision in the cul-de-sac is closed. After entering the space of
      Retzius the endopelvic fascia is incised and the remainder of the procedure
      follows the standard retropubic approach. This technique may be used for salvage
      prostatectomy to avoid rectal injury.

PMID- 9253122
TI  - Intravenous urography revisited in the age of ultrasound and computerized
      tomography: diagnostic yield in cases of renal colic, suspected pelvic and
      abdominal malignancies, suspected renal mass, and acute pyelonephritis.
AB  - The aim of our study was to assess the diagnostic yield of intravenous urography
      (IVU) compared to ultrasound (US) and computerized tomography (CT) in cases of
      renal colic, suspected pelvic and abdominal malignancies, suspected renal mass,
      and acute pyelonephritis. We retrospectively analyzed the case charts of 216
      consecutive patients. The patients had been referred to the Department of
      Radiology by different hospital departments and local general practitioners. All
      had undergone clinical examination, US and IVU, in that order. When deemed
      necessary, conventional tomography was performed. Patients with renal masses also
      underwent CT. In cases without renal colic and normal US examination, the
      subsequent IVU failed to detect any further important pathology. Hydronephrosis
      was equally well detected using US and IVU, however, the level of obstruction was
      better determined using delayed X-ray films. In 24% of cases of renal colics the
      initial US was normal, however, the IVU revealed ureteric obstruction. Repeat US
      8-12 h later always showed hydronephrosis. In 6 of 34 solid renal masses, IVU and
      conventional tomography failed to make the correct diagnosis, but never could the
      patient be spared a subsequent CT. IVU is only indicated if US shows
      hydronephrosis. In cases of renal colic, repeat US is necessary to diagnose the
      possibly developing hydronephrosis. Clinical history, US and a plain abdominal
      image will suffice to make the diagnosis. Renal masses always require CT. In
      these cases, IVU is not necessary. There is no indication left for conventional
      renal tomographies.

PMID- 9253123
TI  - Histological observations of the adhesion and endocytosis of calcium oxalate
      crystals in MDCK cells and in rat and human kidney.
AB  - Adhesion and/or endocytosis of calcium oxalate crystals to the three kinds of
      tubular cells (Madin-Darby canine kidney (MDCK) cells, rat and human kidney) were
      demonstrated morphologically to presume the initial formation of kidney stone.
      After removal of the nonadhesion crystals, the cells were subsequently recultured
      in the vertical position. At various times thereafter, the interactions between
      COM crystals and MDCK cells were evaluated morphologically by SEM. COM crystals
      adhered to the surface of MDCK cells immediately, and the crystals were then
      endocytosed. The microvilli of the cells appeared to play an important role in
      these processes. At later times, some complexes that consist of aggregated
      calcium oxalate crystals and cell debris were observed sporadically. Kidney
      tissues were obtained from male Sprague-Dawley rats which were injected with
      sodium oxalate intraperitoneally. Experimentally induced calcium oxalate crystals
      were evaluated histologically using polarized light microscopy. Some crystals in
      the cortical portion were attached to the tubular epithelium or internalized into
      the luminal membrane. Whereas in the papilla, the aggregated crystals were
      observed lying free from the degenerated tubular lumen along with the cell
      debris. Human kidney tissues were obtained from 38 patients with calcium oxalate
      nephrolithiasis who underwent nephrolithotomy or partial nephrectomy before the
      era of ESWL. The specimens were examined for calcium crystals within the tubular
      lumen, attached to the tubular walls or internalized into the tubular cells, by
      polarized light microscopy. Approximately 50% of the specimens observed crystals
      attached to the tubular cell epithelium and some of them were seen inside the
      tubular cells. In conclusion, crystal-cell interaction resulted in movement of
      crystals from the lumen into the cells by an action of microvilli from the
      results of MDCK cells. However, it was not clear from the results in rats or
      human kidney tissue that crystal adhesion and/or endocytosis might be vital in
      the crystal growth in the kidney.

PMID- 9253124
TI  - Operations on hermaphrodites and castration in Byzantine times (324-1453 AD).
AB  - The authors present and comment on the surgical methods performed on
      hermaphrodites and for castration, which are unique in the medical bibliography
      of Byzantium and were described by the famous physician of the 7th century, Paul
      of Aegina. The latter describes the techniques of reconstruction of
      hermaphrodites learned from the now lost work of the great surgeon of the 1st
      century AD, Leonidas from Alexandria. Paul of Aegina presents, with some ethical
      reservation the scientific methods of castration used by surgeons only in cases
      of acts of God or for serious health reasons, where they were obliged to operate.
      The authors furthermore present the legal position of the state and the church in
      relation to a phenomenon so widespread in Byzantium as castration.

PMID- 9253125
TI  - A transient increase in serum procollagen 1 carboxyterminal peptide following
      effective treatment in prostate cancer patients with bone metastases.
AB  - Procollagen 1 carboxyterminal peptide (P1CP) is thought to be an indicator of new
      bone formation. The present report demonstrates that effective endocrine therapy
      induced an initial increase followed by a delayed decrease in serum levels of
      P1CP and alkaline phosphatase in spite of an immediate decrease in serum PSA and
      PAP and improvement of clinical symptoms in prostate cancer patients with bone
      metastases. The transient increase in P1CP and alkaline phosphatase is a healing
      reaction and is followed by apparent improvement. Short-term effects of endocrine
      therapy on prostate cancer patients with bone metastases should be
      comprehensively evaluated based upon the entire spectrum of clinical and
      laboratory findings including serial changes of serum prostate markers and bone
      markers as well.

PMID- 9253126
TI  - Secondary acute monocytic leukemia occurring during the treatment of a testicular
      germ cell tumor. A case report and review of the literature.
AB  - Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ
      cell tumors is a well-described entity. It also may occur in patients with
      testicular germ cell tumors. We report a case of acute monocytic leukemia
      occurring in a 44-year-old man who received etoposide-based chemotherapy and
      radiotherapy for a recurrent, metastatic testicular germ cell tumor. The patient
      received 14 cycles of systemic chemotherapy for pulmonary and para-aortic lymph
      node metastases following his initial orchiectomy. The total amount of etoposide
      this patient received was 6,400 mg/m2. Leukemia occurred 11 years after
      orchiectomy. A literature review revealed 25 other reported cases of secondary
      leukemias after treatment for testicular carcinoma. It is not clear whether
      chemotherapy, radiotherapy or both are responsible for the secondary leukemias
      seen in these patients.

PMID- 9253128
TI  - Aggressive angiomyxoma of the scrotum.
AB  - Aggressive angiomyxoma is a rare benign tumor, arising in the pelvic soft tissues
      and perineum. It occurs almost exclusively in adult females. It is locally
      infiltrative and exhibiting a high risk of local recurrence. However, it is slow
      growing and does not metastatize. We report a case of aggressive angiomyxoma in
      an adult male which arose in the scrotum.

PMID- 9253127
TI  - Erysipelas and elephantiasis of the scrotum--surgery and drug therapy.
AB  - Elephantiasis of the scrotum is the terminal stage of persistent refractory
      lymphedema. Its debilitating functional and cosmetic effects have significant
      psychological, emotional and social consequences for the affected patient. The
      causal relationship between etiology and recurrent disease is illustrated here by
      2 cases. Therapy options are also discussed. Primary therapeutic success is
      determined by radical surgery, since chronic inflammation and chronic oedema
      mutually foster one another. Metabolic stability, sanitization of infected
      cutaneous areas and the prophylactic administration of antibiotics are essential
      to ensure that the treatment of recurrent erysipelas is successful in the long
      term.

PMID- 9253129
TI  - Temporary spiral stent after endoscopic repair of posttraumatic stricture of
      prostatomembranous urethra.
AB  - We placed a urethral spiral stent for 7 months after an endoscopic excision of
      scar tissue in a patient who had a posttraumatic stricture of the
      prostatomembranous urethra. This procedure immediately allowed the patient to
      void normally and avoided the need for an indwelling urethral catheter.

PMID- 9253130
TI  - Simultaneous occurrence of urothelial bladder carcinoma and primary
      retroperitoneal leiomyosarcoma.
AB  - A case of primary carcinoma of the urinary bladder associated with a primary
      retroperitoneal leiomyosarcoma is presented. Due to the lack of early symptoms,
      diagnosis of the retroperitoneal leiomyosarcoma was late and therefore the
      prognosis was poor. Twelve months after diagnosis the patient died not of the
      bladder tumor, but of the recurrent leiomyosarcoma.

PMID- 9253131
TI  - Adrenal myelolipoma with abdominal pain.
AB  - We report a case of adrenal myelolipoma with abdominal pain. Preoperative
      diagnosis was correctly made by computed tomography and magnetic resonance
      imaging. We have reviewed the literature and discuss the contribution of modern
      imaging techniques to the diagnosis of this tumor.

PMID- 9253132
TI  - Gallbladder metastasis of renal cell carcinoma. A case report and review of the
      literature.
AB  - Although renal cell carcinoma is known to metastasize mainly to lungs, lymph
      nodes, bone, liver, brain or adrenal glands, unusual metastatic spread has been
      published in many case reports and autoptical studies. The gallbladder is rarely
      the site of distant metastases, and in most cases of gallbladder metastasis
      malignant melanoma is the primary tumor. A review of the literature revealed only
      7 cases of renal cell carcinoma metastasizing to the gallbladder, and these were
      mainly found at necropsy. The case of a clinically detected gallbladder
      metastasis is presented.

PMID- 9253133
TI  - ACTH-independent bilateral macronodular adrenocortical hyperplasia caused
      Cushing's syndrome.
AB  - A 53-year-old man who had been followed up for the treatment of hypertension
      presented with a bilateral adrenal mass during a screening CT scan. Other imaging
      studies and biochemical tests suggested Cushing's syndrome caused by a pituitary
      independent and adrenal-dependent bilateral adrenal tumor. A total adrenalectomy
      was performed and the pathological appearance of the surgical specimen showed
      adrenal hyperplasia. Therefore, these findings were considered to be consistent
      with ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). This
      tumor is quite rare and its etiology still remains controversial. We herein
      report this incidentally found AIMAH and also review the pertinent literature.

PMID- 9253134
TI  - Adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia
      presenting as pre-Cushing's syndrome.
AB  - We report a man with pre-Cushing's syndrome due to ACTH-independent bilateral
      macronodular adrenocortical hyperplasia. Plasma ACTH was low and urinary 17-OHCS
      was not suppressed by a high dose of dexamethasone (8 mg), but plasma cortisol
      was responsive to exogenous ACTH. The adrenal glands were enlarged and contained
      multiple nodules composed of large clear cells and small compact cells. The
      steroid levels in the adrenal glands were lower than those in overt Cushing's
      syndrome due to the adrenocortical adenoma. This suggests that the tumor produces
      insufficient amounts of active hormones to have a clinical effect.

PMID- 9253135
TI  - Coping with HIV disease among seropositive women: psychosocial correlates.
AB  - With HIV becoming more of a chronic illness, and with a shift in the demographics
      of the HIV pandemic to women, it is important to understand which psychosocial
      factors relate to positive coping behaviors in HIV-infected women. Additionally,
      socioeconomic factors have frequently confounded the interpretation of results of
      many other studies of stress and coping in HIV-infected individuals. In the
      present study, 58 HIV-infected women were assessed. These women were generally
      well-educated, employed women and therefore did not suffer from socioeconomic
      factors associated with inner city living, commercial sex work, or drug use. We
      performed a discriminant function analysis to determine which of five
      psychosocial variables could discriminate between those who strongly self
      identified with each of three coping styles from those with low self
      identification. The three coping styles included an active, problem solving
      style, a hopeless, given-up style, and a stoic style. Different patterns of
      psychosocial variables discriminated between those who strongly identified with a
      coping style from those who did not. For fighting spirit, the best combination of
      predictors (loadings > .25) were: strong social support, lower loneliness,
      depression, and anger, and a belief in a chance locus of control. The best
      combination of predictors for identification with a helpless coping style were:
      loneliness, depression, and anger, lower social support and less belief in a
      chance locus of control. Stronger identification with a stoic coping style were
      belief in a chance locus of control and lower social support, loneliness, and
      anger. Results of the study point to areas of psychosocial functioning which need
      to be strengthened or diminished in order to maintain effective coping for HIV
      infected women and enhance their quality of life.

PMID- 9253136
TI  - Modeling smoking cessation: exploring the use of a videotape to help pregnant
      women quit smoking.
AB  - This exploratory study examined the acceptability and efficacy of a videotape
      modeling smoking cessation as an adjunct to smoking cessation advice delivered
      during prenatal care. In a randomized controlled trial involving 60 women, we
      compared the delivery of brief smoking cessation advice and a tipsheet to the
      same advice and tipsheet plus provision of the videotape. Outcomes included
      opinions about content and acceptability of the videotape, and smoking behavior
      change during pregnancy. The most highly endorsed features of the videotape were
      seeing other women quitting smoking (77%), dealing with stress and bad feelings
      (69%), talking about what to do with urges to smoke (69%), and discussing ways to
      get support from families and friends (54%). The reported quit rate in the last
      month of pregnancy, validated by exhaled carbon monoxide levels, and including
      women lost to follow-up as smokers, was 19.2% in the intervention group and 0% in
      the comparison group (p = .02). This study suggests that the use of videotapes
      modeling smoking behavior change may increase the effectiveness of the assistance
      in quitting smoking that is generally available in obstetric and family practices
      or public maternity clinics.

PMID- 9253137
TI  - A study of the effects of tamoxifen in the frail elderly: difficulties
      encountered in nursing home research.
AB  - OBJECTIVE: This study was conducted in order to determine whether the effects of
      tamoxifen in elderly, frail nursing home residents are similar to those that have
      been previously reported for younger postmenopausal women. DESIGN: A chart review
      study. SETTING: The Jewish Home and Hospital for Aged (JHHA), a subacute long
      term care facility. PARTICIPANTS: One hundred fifty-eight women who had been at
      the JHHA at any time since 1986. One hundred ten had a history of breast cancer;
      43 of these had been treated with tamoxifen while at the JHHA (Group I), and 66
      had not (Group II). The remaining 49 women had no history of breast cancer (Group
      III). MEASUREMENTS: Data were collected from the time of admission to the JHHA
      through August, 1994 on: chemistry profiles, bone fractures apparently not a
      consequence of metastasis, gynecological parameters, and thromboemboli. RESULTS:
      The lack of pre-admission clinical information presented problems regarding
      research design and the interpretation of our findings. Nevertheless, compared to
      women who had not been treated with tamoxifen, treated women had a significantly
      elevated incidence of vaginal discharge (P = 0.01) and a lower prevalence of
      elevated total cholesterol (P = 0.04). Although not statistically significant,
      they also had decreased levels of low density lipoprotein cholesterol and an
      increased incidence of thromboemboli and bone fractures. CONCLUSIONS: While some
      of the effects of tamoxifen in elderly, frail women are similar to those observed
      in younger, postmenopausal women, others may be different. Our results suggest a
      need for further innovative studies that focus on the consequences of tamoxifen
      treatment in the elderly, frail population.

PMID- 9253138
TI  - Development of the menopause symptom list: a factor analytic study of menopause
      associated symptoms.
AB  - This paper outlines the development of a menopausal symptom checklist amongst a
      community sample of 40 women aged between 45-55 years. Participants completed an
      atheoretical symptom checklist of 56 symptoms that have previously been
      associated with menopause. Following two principal components factor solutions,
      three factors containing 25 symptoms emerged as significant. Interpretation of
      the three factor solution was straightforward with the factors labelled
      psychological, vaso-somatic, and general somatic. These symptoms formed the item
      pool for the Menopause Symptom List (MSL). Unique psychometric properties of the
      MSL make this instrument a useful clinical and research tool. Symptoms are
      operationally defined, scored separately for both frequency of occurrence and
      severity upon 6-point rating scales which provide sensitivity in detecting
      changes in symptomatology. Advantages of the MSL over existing climacteric
      symptom checklists is discussed.

PMID- 9253140
TI  - Psychological effects of weight retained after pregnancy.
AB  - This study is a prospective investigation of the effect of weight retained after
      pregnancy on weight satisfaction, self-esteem and depressive affect, utilising
      the framework provided by expectancy-value theory. Self-report data were obtained
      from 115 women who were in the last month of their first pregnancy, and then
      again a month following the birth. On average women were heavier four weeks after
      having their baby than they were prior to becoming pregnant, and were less
      satisfied with their post-natal weight and shape. They were also slightly heavier
      than they had anticipated, particularly in the case of the younger women. Actual
      post-natal weight proved the most important predictor of psychological well-being
      following birth.

PMID- 9253139
TI  - NGO-promoted women's credit program, immunization coverage, and child mortality
      in rural Bangladesh.
AB  - A growing number of non-governmental organizations (NGOs) are adopting the
      collateral-free credit programs by anchoring them with their social development
      programs aimed at improved program effectiveness and sustainability. Drawing upon
      a sample of 3,564 targeted poor households covered by five small NGOs in rural
      Bangladesh, this study finds that the NGO credit-members as well as those who
      reside in the NGO program area are higher adopters of child immunization than
      those in the non-program area. Similarly, the study found that infant and child
      mortality is lower among the NGO credit members than among the non-members and
      that under five-year deaths of children progressively decline with the increase
      in the doses of vaccines. Implications of these findings are discussed in the
      study.

PMID- 9253141
TI  - Nuclear magnetic resonance timecourse studies of glyphosate metabolism by
      microbial soil isolates.
AB  - 1. Triple Resonance Isotope EDited nmr spectroscopy (TRIED) has been developed to
      detect and examine minute levels of glyphosate metabolites in microbial soil
      isolates. Using stable isotopic labelling (13C and 15N), TRIED allows the
      simultaneous detection of multiple metabolites in crude matrices at submicrogram
      levels. An improvement over earlier techniques where milligrams are needed, TRIED
      can detect 500 ng of triply labelled compound in a crude sample (1:14,000 mass
      ratio) in just hours. 2. TRIED is used here to compare the kinetics and metabolic
      pathways of glyphosate metabolism by two strains of Ochrobactrum anthropi, LBAA
      and S5. Both LBAA and S5 appear to metabolize glyphosate primarily via the
      aminomethylphosphonate (AMPA) pathway, since no detectable levels of glycine or
      sarcosine are observed in the media or lysates of either microbe. The formation
      of N-methylAMPA is common to the metabolism of both microorganisms, but N
      acetylAMPA is observed only in LBAA. N-methylacetamide is detected predominantly
      in media and lysates of S5, although some evidence also points to the formation
      of this metabolite in LBAA. 3. Results are consistent with conventional
      radioactive tracer studies. TRIED nmr provides more specific structural
      information complementary to radiolabel methods. Both nmr and radioactivity
      studies show S5 glyphosate metabolism to be much slower than that of LBAA.

PMID- 9253142
TI  - In vivo and in vitro formation of morphinone from morphine in rat.
AB  - 1. Morphinone, a toxic metabolite, and its glutathione adduct (MO-GSH) were
      identified in the bile of rat after subcutaneous injection of morphine (25 mg/kg)
      by hplc procedures. The amounts of morphinone and MO-GSH excreted in the 12-h
      bile were 0.8 +/- 0.3 and 8.4 +/- 4.3% respectively. 2. The 9000 g supernatants
      of rat, guinea pig, rabbit, mouse, hamster and bovine livers produced morphinone
      from morphine in the presence of either NAD+ or NADP+, NAD+ was a more efficient
      cofactor than NADP+ except in the guinea pig which equally utilized both
      cofactors. With NAD+ as cofactor, the amounts of morphinone formed in rat and
      guinea pig were 5.70 and 5.82 mumol/g liver/30 min respectively and were three-to
      four times those in other species. 3. The enzyme activity responsible for
      formation of morphinone from morphine in the rat was almost exclusively
      distributed in the microsomal fraction, whereas guinea pig, hamster and bovine
      expressed the enzyme activity mainly in the cytosolic fraction. Rabbit and mouse
      gave higher activity in the cytosolic and microsomal fractions respectively, but
      other fractions of both species contained considerable activity. 4. The enzyme
      activities in male and female rat microsomes were characterized with respect to
      developmental pattern, kinetic parameters, pH dependency and susceptibility to
      inhibitors. 5. In conclusion the metabolism of morphine to morphinone in rat was
      confirmed by in vivo and in vitro experiments. It is also suggested that this
      pathway is a common route in morphine metabolism in several mammalian species.

PMID- 9253143
TI  - Cytochrome P450 isozymes responsible for the metabolism of toluene and styrene in
      human liver microsomes.
AB  - 1. Cytochrome P450 isozymes from Asian (31 Chinese subjects) and Caucasian (14
      Finnish subjects) livers were examined for their roles in the metabolism of
      toluene (rates of benzyl alcohol, o- and p-cresol formation) and styrene (rates
      of styrene glycol formation). 2. For toluene, the overall rate of metabolism was
      higher in samples from Finnish than from Chinese subjects. At 0-20 mM toluene,
      the rate of o-cresol formation was significantly higher in Finnish microsomes
      than in Chinese ones. The formation rates of benzyl alcohol and p-cresol in
      Finnish samples were also higher than those of Chinese samples, but only at a
      high substrate concentration (5.0 mM). For styrene metabolism, the Chinese liver
      microsomes showed higher metabolic rates than the Finnish ones at 0.085 mM
      styrene, but not at the higher substrate concentration. 3. Mean expression levels
      of immunochemically detected CYP1A2/1 and CYP2B6 were almost 3-fold higher in
      Finnish microsomes, whereas CYP2E1 was 1.7-fold higher in Chinese samples. 4.
      Correlation analysis showed that CYP2E1 (benzyl alcohol formation) and CYP1A2/1
      (o-cresol formation) contributed to the metabolism of toluene at the low
      substrate concentration, whereas CYP2C8 was the form more actively involved at
      the higher toluene concentrations. At the higher concentration (1.8 mM) of
      styrene, CYP2B6 was most active isozyme to catalyse the formation of styrene
      oxide from styrene. 5. These results suggest that CYP2E1 and CYP1A2/1 are the
      main isoforms responsible for the metabolism of toluene at low substrate
      concentrations in human liver microsomes, CYP2E1 at low styrene concentration,
      and CYP2C8 and CYP2B6 at high concentrations of toluene and styrene respectively.

PMID- 9253144
TI  - Synthesis, isolation and identification of glucuronides and mercapturic acids of
      a novel antiparasitic agent, licochalcone A.
AB  - 1. Four glucuronic acid conjugates of licochalcone A (Lica), and their
      metabolites, have been synthesized using rabbit and pig liver microsomes and
      purified by preparative hplc. 2. The glucuronides were identified as E-Lica 4'-O
      beta-glucuronide, E and Z-Lica 4-O-beta-glucuronide and a mono-glucuronide
      conjugate of a beta-hydroxylated Lica metabolite. The metabolites were identified
      by hplc-nmr (one and two-dimensional nmr) as well as hplc-ms. 3. At pH 8.5 Lica
      reacted with N-acetyl-L-cysteine giving the two epimeric conjugates, which were
      then isolated by preparative hplc and identified by one and two-dimensional nmr
      spectroscopic methods. 4. Only two glucuronic acid conjugates (E- and Z-Lica 4-O
      beta-glucuronide) were found in the urine of rat after i.p. administration of a
      single dose of Lica.

PMID- 9253145
TI  - Irgasan DP 300 (5-chloro-2-(2,4-dichlorophenoxy)-phenol) induces cytochrome P450s
      and inhibits haem biosynthesis in rat hepatocytes cultured on Matrigel.
AB  - 1. The effect of Irgasan DP 300 (5-chloro-2-(2,4-dichlorophenoxy)phenol) on
      cytochrome P450 (P450) induction and haem biosynthesis was studied in rat
      hepatocytes cultured on Matrigel. 2. Irgasan DP 300 significantly induced 7
      benzyloxyresorufin O-debenzylase activity, followed by 7-pentoxyresorufin O
      depentylase and 7-ethoxyresorufin O-deethylase activities. 4-Nitrophenol
      hydroxylase, testosterone 6 beta-hydroxylase and methoxyresorufin O-demethylase
      activities were also slightly increased. The maximum induction of these enzyme
      activities was obtained at the same concentration of 125 microM in the culture
      medium. 3. Immunochemical blots using anti-rat cytochrome P450 antibodies
      revealed that Irgasan DP 300 preferably induced CYP2B1/2 along with a slight
      increase in 3A. These results indicate that Irgasan DP 300 is a phenobarbital
      type inducer. 4. In the absence of exogenous 5-aminolevulinic acid (ALA), slight
      increases in protoporphyrin IX (2.6-fold) and coproporphyrin III (1.3-fold) were
      observed in the Irgasan DP 300-treated cultures. In contrast, when 75 microM ALA
      was present, Irgasan DP 300 (250 microM) caused an extensive accumulation of
      uroporphyrin I (13-fold). 5. Irgasan DP 300 inhibited rat hepatic
      uroporphyrinogen III synthase in vitro. 6. These results indicate that Irgasan DP
      300 produced accumulation of hydroxymethylbilane in rat hepatocytes by inhibiting
      uroporphyrinogen III synthase, and consequently an accumulation of uroporphyrin
      I.

PMID- 9253146
TI  - Sanfetrinem and sanfetrinem-cilexetil: disposition in rat and dog.
AB  - 1. The absorption, distribution, metabolism and excretion of sanfetrinem have
      been investigated in the rat and dog after intravenous (i.v.) administration of
      the radiolabelled parent compound, and oral dosing of the hexetil ester prodrug,
      14C-sanfetrinem-cilexetil. 2. Sanfetrinem-cilexetil was rapidly absorbed and
      hydrolysed pre-systemically to sanfetrinem. The oral bioavailability was 32% in
      rat and 15% in dog. 3. Drug-related radioactivity was distributed in all tissues
      with high levels present in bladder, kidney and liver. The volume of distribution
      was approximately that of extracellular fluid. There was no indication of any
      significant binding or retention to any tissues, including those containing
      melanin. 4. Protein binding of sanfetrinem determined in rat and dog plasma was
      constant over a wide range of concentrations equivalent to 14-18% in dog and
      about 67% in rat plasma. 5. Two metabolites were identified in urine after i.v.
      administration: the open beta-lactam ring derivative (GV173923) and the dimeric
      compound (GV196359). 6. After i.v. dosing the terminal half-life of the unchanged
      drug was 12 min in rat and 35 min in dog. The half-life of the total
      radioactivity was longer due to low levels of metabolites. Of the dose, > 90% was
      excreted in the urine both in rat and dog, and 69% of the dose was excreted as
      unchanged sanfetrinem in rat urine. The radioactivity excreted in the bile
      accounted for 3-7% of the dose.

PMID- 9253147
TI  - Metabolism of 36Cl-ornidazole after oral application to the male rat in relation
      to its antifertility activity.
AB  - 1. The antimycotic ornidazole (a male antifertility agent in rats) was
      synthesized incorporating 36Cl in the chloropropyl sidechain and its metabolism
      was investigated in the male rat after oral ingestion. 2. Blood levels of
      radioactivity were low over the first 24 h and there was no tissue accumulation
      of radioactivity over 48 h. 3. Most of the excreted radioactivity (20% of the
      ingested dose) appeared in the urine within the first 24 h. 4. Three major
      compounds were detected in 0-24-h urine samples and were characterized as
      ornidazole (13% of total radioactivity), Cl- (22%) and 3-chlorolactate (30%), the
      oxidation product of 3-chlorolactaldehyde. 5. No polyuria or glucosuria was
      observed following the oral administration of ornidazole, suggesting that any (R)
      3-chlorolactate produced was insufficient to affect renal metabolism. 6.
      Conversion of ornidazole initially to (R, S)-alpha-chlorohydrin or ultimately to
      the glycolytic inhibitor (S)-3-chlorolactaldehyde could explain its antifertility
      action in the male rat.

PMID- 9253148
TI  - Localization and disposition of a non-peptide angiotensin II type 1 receptor
      antagonist, and its glucuronide metabolite, in rat.
AB  - 1. The disposition of radioactivity of a non-peptide angiotensin II type 1
      receptor antagonist (E4177) has been studied in groups of male rats after a
      single oral 1 mg/kg dose of 14C-E4177 was administered by gavage. We have also
      used light-microscopic autoradiography to investigate the localization of
      radioactivity in the target tissues for this angiotensin II receptor antagonist.
      2. The radioactivity was absorbed quickly, and the maximum blood levels (Cmax)
      were reached at 0.38 +/- 0.14 h after dosing. The concentrations then declined bi
      exponentially with a mean apparent half-life for the first phase (t1/2 alpha) of
      0.46 +/- 0.07 h and a terminal half-life (t1/2 beta) of 6.22 +/- 1.08 h. By 24 h,
      the levels had decreased to 2.7 +/- 1.5% Cmax. The blood levels radioactivity at
      48 h after administration were below the limit of quantification. 3.
      Radioactivity was distributed throughout the body at 15 min after administration.
      Tissues in which radioactivity was present at higher levels than in plasma were
      the liver and kidney. Radioactivity was rapidly eliminated from the tissues and
      was not retained in any individual organ. 4. The major route of excretion was via
      the bile. Since > 90% of the administered radioactivity was recovered by 24 h
      after administration, the excretion was relatively rapid. The major metabolite in
      bile was a glucuronide of E4177 biphenylcarboxylic acid (E4177-Glu). 5. Light
      microscopic autoradiographic observations revealed a strong localization of
      radioactivity throughout the surface cells of the adrenal glomerulosa, the blood
      vessels in kidney and the surface of the aortic smooth muscle cells, which are
      all rich in angiotensin II type 1 (AT1) receptors.

PMID- 9253149
TI  - Diethanolamine absorption, metabolism and disposition in rat and mouse following
      oral, intravenous and dermal administration.
AB  - 1. The disposition of [14C]diethanolamine (DEA) (1) was determined in rat after
      oral, i.v. and dermal administration, and in mouse after dermal administration.
      2. Oral administration of DEA to rat was by gavage of 7 mg/kg doses once and
      after daily repeat dosing for up to 8 weeks. Oral doses were well absorbed but
      excreted very slowly. DEA accumulated to high concentrations in certain tissues,
      particularly liver and kidney. The steady-state of bioaccumulation was approached
      only after several weeks of repeat oral dosing, and the half-life of elimination
      was approximately 1 week. 3. DEA was slowly absorbed through the skin of rat (3
      16% in 48 h) after application of 2-28 mg/kg doses. Dermal doses ranging from 8
      to 80 mg/kg were more readily absorbed through mouse skin (25-60%) in 48 h of
      exposure, with the percent of the applied dose absorbed increasing with dose. 4.
      Single doses (oral or i.v.) of DEA were excreted slowly in urine (c. 22-25% in 48
      h) predominantly as the parent compound. There was minimal conversion to CO2 or
      volatile metabolites in breath. The profile of metabolites appearing in urine
      changed after several weeks of repeat oral administration, with significant
      amounts of N-methylDEA and more cationic metabolites appearing along with
      unchanged DEA.

PMID- 9253150
TI  - Dose-dependent effects of acute lindane treatment on Kupffer cell function
      assessed in the isolated perfused rat liver.
AB  - 1. Twenty-four hours after lindane exposure (5-60 mg/kg) a dose-dependent
      increase in the serum and hepatic levels of the insecticide was observed. Both
      the basal rate of O2 consumption and the sinusoidal efflux of lactate
      dehydrogenase (LDH) by the perfused rat liver was enhanced after the
      administration of 20-60 mg lindane/kg. 2. The administration of low doses of
      lindane (5-20 mg/kg) increased carbon uptake and the carbon-induced O2
      consumption by the perfused liver, effects that were abolished by pretreatment
      with the Kupffer cell inactivator gadolinium chloride (GdCl3). These parameters
      were not modified at the higher doses of lindane used (40-60 mg/kg). 3. In the
      dose range of 20-60 mg lindane/kg, carbon infusion led to a further increase in
      liver LDH efflux over values found in its absence, an effect that was markedly
      diminished by GdCl3 in rat treated with 20 mg lindane/kg, being unaltered by
      GdCl3 in animals given 60 mg/kg. 4. It is concluded that lindane induces a dose
      dependent biphasic effect on Kupffer cell function, which could be conditioned by
      differential membrane perturbation actions of the insecticide that progressively
      accumulates in the liver, thus altering receptor-mediated and enzymatic processes
      related to colloidal carbon phagocytosis. Increased Kupffer cell function at low
      doses of lindane leads to enhanced liver injury. However, this feature of lindane
      intoxication at higher doses (60 mg/kg) is independent of Kupffer cell activity
      and seems to be determined by an oxidative stress mechanism induced at the
      parenchymal cell level.

PMID- 9253151
TI  - Patterning of immobilized antibody layers via photolithography and oxygen plasma
      exposure.
AB  - A novel technique for patterning immobilized antibody layers based upon
      photolithography and oxygen plasma exposure has been developed. Mouse monoclonal
      antibodies specific for thiabendazole (a post-harvest fungicide and veterinary
      anthelmintic) were covalently linked through free amine groups to aminosilanized
      silicon dioxide films using glutaraldehyde. Immobilized antibody layers were
      stabilized with sucrose, dehydrated, and stored refrigerated with desiccant.
      Photolithographic patterning was performed with a positive photoresist with
      modified bake temperatures and times, selective UV exposure with a contact mask,
      and aqueous alkaline solubilization of exposed resist. Exposed regions of
      immobilized antibody were then removed by exposure to a low power, radio
      frequency oxygen discharge. Residual resist was stripped with acetone. Successful
      patterning was demonstrated by challenging surfaces with goat anti-mouse antibody
      conjugated to tetramethylrhodamine isothiocyanate. Sucrose stabilization was
      necessary for antibody to undergo photoresist processing without loss of binding
      activity. Challenge with enzyme linked antigen of oxygen plasma exposed antibody
      layers demonstrated that plasma treatment completely neutralized antibody capture
      ability. Ellipsometry measurements of oxygen plasma exposed antibody layers
      indicated complete removal of immobilized antibodies. Fluorescent imaging
      demonstrated smallest line widths of 2-3 microns.

PMID- 9253152
TI  - A cell-based immunobiosensor with engineered molecular recognition--Part II:
      Enzyme amplification systems.
AB  - Immune cells in vivo routinely perform highly selective immunosensing in blood
      and tissues as part of their normal immune surveillance functions. We have been
      investigating the potential of exploiting the immunosensing detection abilities
      of excitable immune cells (i.e. the mast cell) for the development of whole cell
      immunobiosensors. A key feature is that these immune cells can be selectively
      engineered to recognize specific antigens in vitro. In the presence of antigen,
      these cells undergo excitable activation responses which result in increased
      metabolism and the exocytosis of stored intracellular mediators. We have
      previously determined that mast cell metabolic responses can be thermally
      transduced in real time, thus indicating the possibility of whole cell
      thermoelectric immunobiosensing. In this work we investigated the use of enzyme
      amplification systems to enhance the direct transduction of immune cell responses
      to analyte. It was found that with appropriate enzymes, peak outputs occurred
      within approximately 5 min (4-20 times faster than without enzymes) and peak
      response magnitudes were up to nine-fold greater than without enzymes.

PMID- 9253153
TI  - Evanescent wave fibre optic sensor for detection of L. donovani specific
      antibodies in sera of kala azar patients.
AB  - An easy-to-use technique for detection of antibodies specific for the parasite L.
      donovani in human serum sample has been developed. The method is based on an
      evanescent wave generated from a tapered configuration of decladded optical fibre
      and does not require any volumetric measurement. Tapered fibres are immobilized
      with the purified cell surface protein of L. donovani by covalent bonding.
      Treated fibres are incubated with the patient serum for 10 min followed by
      incubation with goat anti human IgG tagged FITC. Fluorescent intensity from the
      fibre has been shown to be proportional to L. donovani specific antibodies
      present in the test sera. Direct readings can be obtained after signal
      enhancement through a photomultiplier tube within 5 min. The system, when tested
      on 12 positive sera, did not show any false negative result. Also, no false
      positive result was obtained with serum samples of patients infected with
      leprosy, tuberculosis, typhoid and malaria, showing the specificity of the sensor
      and efficacy of the technique.

PMID- 9253154
TI  - Development of an amperometric flow injection immunoanalysis system for the
      determination of the herbicide 2,4-dichlorophenoxyacetic acid in water.
AB  - An amperometric flow injection immunoanalysis (FIIA) system based on an
      immunoreactor with immobilized biocomponents on a silica surface has been
      developed for the determination of the herbicide 2,4-dichlorophenoxyacetic acid
      (2,4-D). In the antigen coating mode the hapten was immobilized and monoclonal
      primary antibody against 2,4-D together with alkaline phosphatase (AP)-labelled
      secondary antibody were used as sensing elements in a titration assay. In the
      antibody coating mode a biotinylated monoclonal antibody was immobilized on the
      surface of the immunoreactor and a 2,4-D-AP-conjugate was used for detection. For
      electrochemical measurements p-aminophenol enzymatically generated from p
      aminophenyl phosphate was oxidized at a carbon working electrode at +150 mV
      versus Ag/AgCl. The system enabled the determination of 2,4-D in drinking water
      samples in the range from 0.2 to 70 micrograms/l. The whole system was computer
      controlled with a measuring time of 12 min for one determination.

PMID- 9253155
TI  - Multianalyte biosensors on optical imaging bundles.
AB  - We present an optical biosensor design that expands the utility of enzyme
      biosensors. These biosensors are fabricated by site-selective photodeposition of
      analyte-sensitive polymer matrices on optical imaging fibres. These dual-analyte
      arrays allow for the simultaneous, independent measurement of the analyte of
      interest and the transducing analyte. The first integrated optical-biosensors
      using this design have been prepared that allow both the dependent and
      independent analytes to be measured simultaneously, for example penicillin and pH
      (Healey & Walt, 1995) or glucose and O2 (Li & Walt, 1995). Independent
      measurement of the transducing analyte allows penicillin or glucose to be
      quantitated in the presence of a concurrent pH or O2 change, respectively.
      Penicillin can be measured in the range 0.25-10.0 mM in the pH range 6.2-7.5.
      Glucose can be measured in the range 0.6-20.0 mM in the O2 range 20-100%. The
      utility of the sensor design was demonstrated by using the penicillin-dual
      analyte biosensor to quantitate penicillin produced during a Penicillium
      chrysogenum fermentation.

PMID- 9253156
TI  - Specific binding of low molecular weight ligands with direct optical detection.
AB  - The characterization of low molecular weight ligand interaction with receptor
      molecules is of importance for the investigation of biological processes and for
      drug research. We report on the investigation of the binding of low molecular
      weight ligands to immobilized receptors by label-free detection. Reflectometric
      interference spectroscopy, an optical transducer which allows the monitoring of a
      few picograms per square millimetre changes in surface coverage, was used to
      study two model systems. In both cases detection of the binding event was
      successful. High affinity binding of biotin to immobilized streptavidin was
      clearly detectable at receptor surface concentrations as low as 1-2 x 10(10)
      binding sites/mm2. Linear correlation between the receptor surface concentration
      and the response to biotin binding was observed. Using immobilized DNA, we
      investigated the binding of common intercalators with respect to kinetics and
      thermodynamics by evaluation of the association and the dissociation part of the
      binding curve. Bi-exponential increase and decrease of intercalator loading was
      observed, indicating complex interaction kinetics. The four structurally
      different intercalators showed significant distinction in binding kinetics and
      equilibrium signals. Improvement of experimental parameters is required to obtain
      more reliable kinetic data.

PMID- 9253157
TI  - Amperometric lactate oxidase catheter for real-time lactate monitoring based on
      thin film technology.
AB  - An amperometric lactate oxidase catheter has been developed for in vivo
      application to real-time lactate monitoring. The electrochemical behaviour of the
      1 x 3 mm Pt-Ag/AgCl thin film electrode is not significantly influenced by
      lactate oxidase-polyurethane covering. Gamma-irradiation (25 kGy) is suitable for
      the sterilization procedure. The final lactate catheter is characterized by a
      linear concentration range between 0.5 and 20 mmol/l lactate with a sensitivity
      around 2 nA mmol-1 l-1 lactate. The accuracy is demonstrated by the measurement
      of control sera. Both physiological and pathological materials correlate well
      with the declared values. The dry stored lactate catheter needs about 10 min for
      hydration and is characterized by response times t98% of less than 2 min. Ex vivo
      whole blood measurements using the lactate catheter (y) give a correlation with
      the BIOSEN Med L (x) of y = (1.010x + 0.513) mmol/l (r = 0.9748). Lactate values
      obtained by continuous catheter operation ex vivo correlate well with those
      obtained by BIOSEN Med L. First subcutaneous implantation (dog) underlines the
      characteristics obtained ex vivo: after 30 min hydration the lactate catheter
      follows the lactate concentration measured ex vivo with samples from the leg vein
      by BIOSEN Med L.

PMID- 9253158
TI  - Transport, metabolism and distribution space of octanoate in the perfused rat
      liver.
AB  - The scope of the present work was to investigate the metabolism and the passage
      of octanoate from albumin into the phospholipid bilayer of the plasma membrane
      and from thence into the cell space. The experiments were done in the isolated
      perfused rat liver with infusions of albumin and octanoate at various
      concentrations. Once steady-state conditions were attained, trace amounts of [1
      14C]-octanoate, [131 I]-albumin and [3H]-water were injected simultaneously and
      the effluent perfusate was fractionated. The normalized dilution curves were used
      for model analysis. The model which gives the best fit to the experimental
      results and which also produces the most consistent parameters is one that
      presupposes a rapid distribution of octanoate into the cell membrane and a slow
      transfer from the cell membrane into the cytosol. The concentration dependence of
      the distribution between the membrane and the extracellular space is parabolic,
      suggesting that octanoate changes the properties of the cell membrane when
      present at higher concentrations. The passage from the cell membrane into the
      cell space is relatively slow and limits metabolic transformation partly or
      totally, depending on the octanoate concentration in the plasma membrane. The
      rapid transfer of octanoate from the albumin space into the plasma membrane
      corroborates previous measurements of the dissociation of the albumin-octanoate
      complex.

PMID- 9253160
TI  - Different progress of MDCK cell death after infection by two different influenza
      virus isolates.
AB  - The effect of influenza strains A (H3N2) and B, isolated during the seasons of
      1994 and 1995 in the Czech Republic, on MDCK cells was studied. Various
      concentrations of virus and conditions of nutrition were used during the cell
      culture. The virus replication and consequently fragmentation of genomic DNA
      together with cytotoxicity were investigated in the absence and presence of 10
      per cent calf serum. Virus replication, regardless of type A or B, caused earlier
      DNA fragmentation in comparison to non-infected cells in tissue culture. The
      results showed that the influenza B strain had a greater cytotoxic effect on MDCK
      cells than influenza A. A higher infection dose of influenza A virus accelerated
      the onset of apoptosis; conversely, a higher infection dose of influenza B virus
      delayed the onset of apoptosis. The absence of serum enhanced the progress of
      influenza-induced apoptosis in conditions in vitro.

PMID- 9253159
TI  - Rapid induction of Fas antigen mRNA expression in vivo by cycloheximide.
AB  - The effect of administration into rats of cycloheximide on the expression of
      genes, such as tissue transglutaminase, testosterone-repressed prostate message
      2, Fas antigen, bcl-2, DNase I, and poly(ADP-ribose) polymerase, which were
      believed to be involved in the mechanism of apoptosis, was studied. While the
      effect of cycloheximide on the expression of genes other than Fas antigen was
      modest, only the expression of Fas antigen was elevated rapidly in most of the
      organs examined. A possible direct effect of cycloheximide on cells per se to
      induce Fas antigen mRNA expression was demonstrated by the tissue culture study
      using L929 fibroblast cells, although the magnitude of the induction detected in
      vitro was small compared with that in vivo. This induction of Fas antigen mRNA by
      cycloheximide is a first report on the modulation of Fas antigen mRNA expression
      in vivo.

PMID- 9253161
TI  - Effects of retinoids on the production of tumour necrosis factor-alpha and nitric
      oxide by lipopolysaccharide-stimulated rat Kupffer cells in vitro: evidence for
      participation of retinoid X receptor signalling pathway.
AB  - Kupffer cells play important roles in the development of liver injury by
      producing cytokines and free radicals. In consequence inhibition of these
      inflammatory mediators will be one of the targets for treating liver diseases.
      Retinoids modulate a wide variety of functions of monocytes/macrophages. Cellular
      effects of retinoids are mediated by two families of nuclear receptors, retinoic
      acid receptors (RARs) and retinoid X receptors (RXRs). We examined the effects of
      several kinds of natural and synthetic retinoids on the production of tumour
      necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) by LPS-stimulated rat
      Kupffer cells in vitro. Of the various retinoids tested, 9-cis-retinoic acid (9
      cis-RA) and Ro 13-6307 which are agonists of both RARs and RXRs, suppressed the
      production of TNF-alpha and NO in a concentration-dependent fashion, whereas
      three types of RAR-selective agonists, Ro 13-7410, Ro 40-6055 and Ro 19-0645 did
      not show any effect. Furthermore, the RAR alpha antagonist, Ro 41-5253, did not
      prevent the effects induced by 9-cis-RA. The results suggest that these effects
      of 9-cis RA and Ro 13-6307 were induced by the RXRs-dependent signalling pathway.

PMID- 9253162
TI  - Effect of adrenaline on lymphocyte metabolism and function. A mechanism involving
      cAMP and hydrogen peroxide.
AB  - This study examined the effect of adrenaline on lymphocyte metabolism and
      function. The following parameters were addressed: cell proliferation, glucose
      and glutamine metabolism as indicated by the measurement of enzyme activities,
      the utilization of metabolites and production and oxidation of substrates. We
      also evaluated the involvement of beta-receptors in this response as well as the
      possible effect of cAMP and hydrogen peroxide in the process of lymphocyte
      activation by adrenaline. The results indicated that adrenaline is able to induce
      metabolic changes in lymphocytes that are related to enhanced proliferative
      capacity, but under physiological conditions fails to initiate the process, the
      catecholamine could, increase cell proliferation via increased production of H2O2
      by macrophages, since this reactive oxygen intermediate can act as a trigger for
      lymphocyte activation. The results also showed that distinct populations of
      lymphocytes present different responses to adrenaline activation, as demonstrated
      by cells obtained from the same site but exposed to different mitogens such as
      LPS and ConA.

PMID- 9253163
TI  - Temperature dependency of calcium responses in mammary tumour cells.
AB  - Changes of intracellular calcium concentration ([Ca2+]i) induced by the
      extracellular application of ATP and bradykinin in mouse mammary tumour cells
      (MMT060562) were investigated by image analysis of fluo-3 fluorescence at 24
      degrees C and 35 degrees C. ATP (0.1-100 microM) and bradykinin (0.1 nM-1 microM)
      induced the increase of [Ca2+]i at both temperatures and Ca(2+)-depletion did not
      affect these [Ca2+]i responses. Both [Ca2+]i responses became more sensitive at
      35 degrees C than at 24 degrees C. A clear latency of [Ca2+]i increase after the
      application of the agonists was observed, and it changed with the concentration
      of the agonist. As concentrations of ATP or bradykinin became lower, the latency
      and rise time became longer. At higher concentrations, the latency and rise time
      approached a constant value. The latency shortened remarkably at 35 degrees C.
      These results suggested the involvement of a regenerative or threshold process in
      the [Ca2+]i responses in mammary tumour cells.

PMID- 9253164
TI  - In vitro stimulation by tumour cell media of [3H]-thymidine incorporation by
      mouse spleen lymphocytes.
AB  - Mouse spleen lymphocyte (SL) cells show a three to four-fold increase in [3H]
      thymidine incorporation when incubated in tumour cell media, or in media
      containing tumour cell cytosol. Agarose gel chromatography of both [3H]-thymidine
      labelled tumour cell media and cytosol shows a sharp peak of DNA-associated
      material eluting at about 60 kDa. This DNA-associated material is imported
      rapidly and efficiently by SL cells and is recoverable from their cytosol. The
      stimulating effect on SL cell thymidine incorporation resides primarily, if not
      exclusively, in this extruded/cytosolic 60 kDa DNA material. Tumour cells
      incubated in media containing normal or liver, but not tumour, cytosol show a
      reduced rate of [3H]-thymidine incorporation, indicating competition between
      normal and tumour associated DNA complexes. The results indicate that such cell
      extruded DNA complexes may transmit 'genetic messages' to other cells, and are
      discussed in terms of interactions in the tumour-bearing host.

PMID- 9253165
TI  - Introducing specific antibodies into electropermeabilized cells is a valuable
      tool for eliminating specific cell functions.
AB  - A technique is established for the role of intracellular proteins to be
      eliminated and thereby gives information about their specific role in signal
      transduction within cells. Rat pancreatic islets as well as INS-1 cells (an
      insulin secreting cell line) were electrically permeabilized in order to
      introduce high molecular weight compounds. Optimized conditions were five
      exposures with 15-s intervals, tau = 200 ms, an electric field of 1.36 kV per 0.4
      cm in a specific permeabilization buffer at a calculated Ca++ concentration of 5
      x 10(-8) M. In electroporation control experiments the spectrophotometrically
      measured uptake of the cell membrane-impermeable propidium iodide, FITC-labelled
      dextran (MW approximately 4000) and FITC-labelled antibodies (MW approximately
      150,000) was established as being 81.5 +/- 5.0, 82.7 +/- 3.0 and 81.0 +/- 1.0 per
      cent of maximum, respectively. These data were corroborated qualitatively by
      visualizing microscopically the fluorescence of the FITC-labelled compounds in
      islets as well as in INS-1 cells. The cells appear to reseal since control
      experiments indicated a short-lived outflow of lactate dehydrogenase (MW of
      140,000 which is similar to that of antibodies) and of insulin for the first 15
      20 min. After electroporation the cells were functionally intact, i.e. responded
      to the stimulus carbachol (CCh). Only 18.0 +/- 10.1 per cent of cells had not
      resealed after 2 h (propidium iodide uptake measured at various time intervals
      after electroporation). As was shown recently the effect of specific compounds
      such as CCh and CCK8 on insulin release was eliminated selectively by antibodies
      against specific G proteins thus proving this method to be a valuable tool. In
      conclusion, adding antibodies to electrically permeabilized cells is a valuable
      tool for eliminating a specific cell function in order to elucidate the specific
      role of intracellular compounds. This method can probably be used for testing the
      specific role of other proteins in cell functions.

PMID- 9253166
TI  - Inhibition of human tumour cell proliferation by analogues of adenosine.
AB  - The effects of adenosine and several structural analogues of adenosine upon
      thymidine incorporation into human tumour cells and rat cervical lymphocytes were
      investigated. The analogue NECA, which has equal specificity for the A1 and A2
      receptor, had the most inhibitory effect on lymphocyte proliferation while the A1
      agonists had limited effects, suggesting that these cells possess principally A2
      adenosine receptors. In the case of human tumour cells, however, the most
      inhibitory effect on proliferation was obtained with the A1-specific analogues.
      The general order of inhibitory effects of adenosine analogues on thymidine
      incorporation in human tumour cells was: S-ENBA > CPA = R-PIA > S-PIA > NECA.
      These findings suggest that in the cells presently studied the A1 adenosine
      receptor predominates. Removal of exogenous adenosine by growth in the presence
      of adenosine deaminase inhibited thymidine incorporation. The effect of adenosine
      removal lends further support to the proposal that adenosine has some, as yet
      unidentified, regulatory role in the control of human tumour cell proliferation.

PMID- 9253167
TI  - Fungal microflora biodiversity as a function of pollution in Oued Sebou
      (Morocco).
AB  - An inventory of the fungal microflora present in sediments collected at 11 sites
      along Oued Sebou has been established. The influence of some climatic parameters
      (temperature, rainfall) and of pollution on the composition of the fungal
      communities has been questioned. Emericella nidulans, Eurotium amstelodami,
      Neosartotya fisheri var. glabrum (Ascomycetes), Dreschslera biseptata
      (Dematiaceae), Penicillium citrinum (Mucedinaceae) and Phoma sp. (Sphaeropsidale)
      can be considered as strains sensitive to pollution. Penicillium janthelinum,
      Trichoderma koningii (Mucedinaceae) and Candida albicans (Yeast) were found only
      at the most polluted sites; Talaromyces flavus (Ascomycete) Rhodotorula rubra,
      Saccharomyces cerevisiae (Yeasts) and Fusarium oxysporum (Tuberculariales) were
      more often found at heavily polluted sites than at lightly polluted ones.

PMID- 9253168
TI  - Calculation of soil-water and benthic sediment partition coefficients for
      mercury.
AB  - To accurately model mercury transport to water bodies, an assessment of this
      pollutant's behavior in the watershed is critical. Partition coefficients,
      defined as an estimate of the ratio of the pollutant concentration sorbed onto
      soil/sediment particles to the pollutant concentration dissolved in pore water at
      equilibrium, is an important term in multimedia models. In this paper, partition
      coefficients are calculated for two broad species of mercury: inorganic mercuric
      mercury (Hg-II) and methylmercury (MHg). Although there is considerable
      variability in the calculated values, the approximate mean values for the soil
      water partition coefficients range from 3.3 x 10(3) to 6.0 x 10(4) L/kg for Hg-II
      and 2.0 x 10(1) to 6.7 x 10(3) L/kg for MHg. For the benthic sediment partition
      coefficients, the values range from 5.7 x 10(3) to 9.9 x 10(5) L/kg for Hg-II,
      and 6.5 x 10(2) to 1.1 x 10(5) L/kg for MHg.

PMID- 9253169
TI  - Mercury emissions from dental chairs by disinfection.
AB  - Dental aspirator kits are equipped with amalgam separators, which eliminate the
      particulate matter from the effluent. When the aspirator kits are disinfected,
      the disinfectant solution is in contact with the separated amalgams over night
      and over the weekend. Oxidizing components of the disinfectants dissolve mercury
      from the separated amalgam. The dissolved mercury is released into the
      environment along with the effluent on the beginning of the following workday.
      The degree of mercury remobilization depends on the amount and oxidizing power of
      the disinfectant components. The mercury concentrations measured in the effluent
      of the aspirator kits after the application of seven different disinfectants were
      18.4 micrograms/l-1396 micrograms/l. The emission of mercury by dental aspirator
      kits is lowered substantially by using disinfectants which contain no oxidizing
      substances. Disinfecting of dental aspirator kits for hygienic reasons is not
      necessary. Therefore we propose only cleaning rather than disinfecting dental
      aspirator kits.

PMID- 9253170
TI  - Bioaccumulation and lack of toxicity of octachlorodibenzofuran (OCDF) and
      octachlorodibenzo-p-dioxin (OCDD) to early-life stages of zebra fish (Brachydanio
      rerio).
AB  - Previous studies with octachlorodibenzo-p-dioxin (OCDD) and
      octachlorodibenzofuran (OCDF) in juvenile or adult fish exposed via water
      revealed no toxicity, despite significant bioaccumulation. With 2,3,7,8
      tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), the fish early-life stage study has
      been shown to be the most sensitive test system. Therefore, the effects of OCDD
      and OCDF on the early-life stages of zebra fish (Brachydanio rerio) were
      determined during a flow-through test based on a column generator method. No
      statistically significant effect of OCDD and OCDF on the survival and hatching
      time of the eggs was found. Furthermore, no effects on survival, weight, general
      appearance or behaviour of the larvae were observed at the end of the exposure
      period of 32 days. GC-MS analysis of test solution samples revealed geometric
      mean measured concentrations of 32 (OCDD) and 34 ng/l (OCDF), respectively.
      Concentrations in surviving larvae at the end of the study were 61 (OCDD) and 94
      (OCDF) micrograms/kg, respectively. These concentrations in zebra fish larvae
      were several orders of magnitude higher than concentrations in fish collected
      from the wild. In a review of the available laboratory fish experiments, we found
      a lack of biomagnification of OCDD and OCDF. We do not expect to find adverse
      effects of these compounds on the aquatic environment.

PMID- 9253171
TI  - Chemical and mutagenic analysis of volatile organic compounds in Raleigh air
      samples at three different elevations before, during, and after Hurricane Gordon.
AB  - Volatile organic compounds (VOCs) were collected and measured at a television
      tower 10 km southeast of downtown Raleigh, North Carolina at three different
      levels (Surface, < 1 m; Mid, 240 m; and Top, 433 m) during the summer and fall of
      1994. The combined presence of ozone, arenes, and nitrogen oxides (NOx) suggested
      possible nitration of arenes during atmospheric mixing. Air samples, therefore,
      were collected using XAD-filled canisters at each level on the tower prior to,
      during, and after Hurricane Gordon. Collected air samples were Soxhlet extracted
      and analyzed with the Salmonella typhimurium microsuspension mutagenicity assay
      using strains YG1021 and YG1026 which are sensitive to nitrarenes. Significant
      mutagenicity was observed only in the Top and Mid level samples for the post
      hurricane, normal weather air samples. Surface samples were not mutagenic, which
      suggests the long-range transport of these mutagenic nitrarenes.

PMID- 9253172
TI  - Carrier effects of dosing the H4IIE cells with 3,3',4,4'-tetrachlorobiphenyl
      (PCB77) in dimethyl sulfoxide or isooctane.
AB  - A rat hepatoma cell line, H4IIE, serves as a bioassay tool to assess the
      potential toxicity of dioxin-like chemicals, including polychlorinated biphenyls
      (PCB) in environmental samples. PCB exposure to these cells induces cytochrome
      (CYP) P4501A1 activity in a dose-dependent fashion, thus allowing assessment of
      mixtures. The objective of this study was to determine the effect of different
      carriers, dimethyl sulfoxide (DMSO) and isooctane on the concentrations of PCBs
      in the H4IIE cells and induction of CYP1A1 activity as measured by
      ethoxyresorufin O-deethylase (EROD) activity. H4IIE cells were dosed with three
      micrograms of UL-14C-PCB77/plate dissolved in DMSO or isooctane, and were
      harvested at sequential time periods for 4 days. PCB77 concentration and EROD
      activity were measured in the cells. EROD activity was greater when using DMSO as
      compared to isooctane, while there was no difference in the distribution of PCB77
      derived radioactivities within the cell culture system based upon the carrier
      solvent used to deliver PCB77.

PMID- 9253173
TI  - Artemia mitochondrial genome: molecular biology and evolutive considerations.
AB  - During the last two decades an increasing amount of information has been
      accumulated regarding the gene structure and organization of the mitochondrial
      genome from various organisms. Many studies carried out mainly in mammals, have
      contributed to the knowledge of the basic elements involved in the replication
      and transcription of mitochondrial DNA. However, very little is known about these
      processes in invertebrates. In this review we discuss our current knowledge of
      the animal mitochondrial genetic system and briefly summarize the structure of
      the Artemia mitochondrial genome, the characteristics of its transcriptional
      machinery and how its expression is controlled during early development, in
      relation with what is known in other organisms. Artemia is the only crustacean
      where the mtDNA has been studied at this level of detail up to date.

PMID- 9253174
TI  - Crustacean muscle plasticity: molecular mechanisms determining mass and
      contractile properties.
AB  - Two crustacean models for understanding molecular mechanisms of muscle plasticity
      are reviewed. Metabolic changes underlying muscle protein synthesis and
      degradation have been examined in the Bermuda land crab, Gecarcinus lateralis.
      During proecdysis, the claw closer muscle undergoes a programmed atrophy, which
      results from a highly controlled breakdown of myofibrillar proteins by Ca(2+)
      dependent and, possibly, ATP/ubiquitin-dependent proteolytic enzymes. The
      advantage of this model is that there is neither fiber degeneration nor
      contractile-type switching, which often occurs in mammalian skeletal muscles. The
      second model uses American lobster, Homarus americanus, to understand the genetic
      regulation of fiber-type switching. Fibers in the claw closer muscles undergo a
      developmentally-regulated transformation as the isomorphic claws of larvae and
      juveniles differentiate into the heteromorphic cutter and crusher claws of
      adults. This switching occurs at the boundary between fast- and slow-fiber
      regions, and thus the transformation of a specific fiber is determined by its
      position within the muscle. The ability to predict fiber switching can be
      exploited to isolate and identify putative master regulatory factors that
      initiate and coordinate the expression of contractile proteins.

PMID- 9253175
TI  - Molecular phylogenetics of a protein repair methyltransferase.
AB  - Protein-L-isoaspartyl (D-aspartyl) O-methyltransferase (E.C. 2.1.1.77) is a well
      conserved and widely distributed protein repair enzyme that methylates isomerized
      or racemized aspartyl residues in age-damaged proteins. We exploited the
      availability of protein sequences from 10 diverse animal, plant and bacterial
      taxa to construct a phylogenetic tree and determine the rates of amino acid
      substitution for this enzyme. We used a likelihood ratio test to show that this
      enzyme fulfills the conditions for a molecular clock. We found that the rate of
      substitution is 0.39 amino acid substitutions per site per 10(9) years and
      remains relatively constant from bacteria to humans. We argue that this degree of
      sequence conservation may result from the functional constraints necessitated by
      the requirement to specifically recognize altered aspartyl but not normal
      aspartyl residues in proteins. Relative rate analysis of the Caenorhabditis
      elegans sequence suggests that the amino acid substitution rate in the nematode
      lineage may be higher than that in other lineages and that the divergence of
      nematodes may have been a more recent event than suggested by previous analysis.

PMID- 9253176
TI  - Development of an ELISA for chum salmon (Oncorhynchus keta) growth hormone.
AB  - A specific and sensitive enzyme-linked immunosorbent assay (ELISA) was developed
      for the measurement of low levels of serum growth hormone (GH) in chum salmon
      (Oncorhynchus keta). The antiserum to GH (a-rsGH) was obtained from a rabbit
      immunized with recombinant chum salmon GH. The noncompetitive ELISA was performed
      by a sandwich method using a-rsGH rabbit IgG as the first antibody, its
      biotinylated Fab' fragment as the second antibody, and the avidin-biotin reaction
      for signal amplification. This assay could be run in 3 days and routinely
      detected GH at concentrations as low as 0.5 ng/ml. The development of an ELISA
      for GH made possible quantification of serum GH levels. In this assay system,
      parallel dilution curves were obtained using purified chum salmon GH and GH's
      from several species of the genus Oncorhynchus.

PMID- 9253177
TI  - Characterization of Cu,Zn superoxide dismutase from the bathophile fish,
      Lampanyctus crocodilus.
AB  - Cu,Zn SOD from the bathophile teleost Lampanyctus crocodilus (LSOD) shows a high
      degree of homology with the sequence of the enzymes from other teleostean fish
      species. The catalytic properties of LSOD are very similar to those of the bovine
      enzyme, albeit with higher sensitivity to thermal denaturation. The apparent
      molecular mass of LSOD (37.6 KDa) is higher than the other Cu,Zn SOD variants
      studied. The aminoacid sequence of LSOD reveals interesting substitutions
      compared to the bovine enzyme. These are discussed in view of the particular
      environmental conditions to which L. crocodilus is adapted.

PMID- 9253178
TI  - Structure and expression of bombyxin E1 gene: a novel family gene that encodes
      bombyxin-IV, an insect insulin-related neurosecretory peptide.
AB  - A bombyxin gene encoding precursor molecule for bombyxin-IV, one of the insulin
      related neurosecretory peptide of the silkmoth Bombyx mori, has been cloned and
      characterized. The nucleotide sequence of this gene and its deduced amino acid
      sequence deviate moderately from those characterized previously for the family A,
      B, C and D bombyxin genes. The gene encoding the bombyxin-IV precursor was
      therefore defined into a novel family E and designated as gene E1. The bombyxin
      E1 transcript in Bombyx brain was shown to locate in four pairs of medial
      neurosecretory cells, which also produce other bombyxin family mRNAs, and the
      amount of the E1 transcript did not change markedly during the fifth larval
      instar. Genomic Southern hybridization indicated that the Bombyx haploid genome
      contained a single copy of the bombyxin family E gene.

PMID- 9253179
TI  - A comparative study on the functional properties of the wild European mouflon and
      domestic sheep hemoglobins.
AB  - The functional properties of Hb B of the wild European mouflon (Ovis gmelini
      musimon), Hb B of domestic sheep (Ovis aries), and Hb C isolated from anemic
      mouflon were investigated. Mouflon and sheep Hbs appear to be very similar in
      their response to organic anions and protons, whereas sheep Hb B displays an
      oxygen affinity lower than that of mouflon Hb B and sheep Hb A. Mouflon Hb B and
      Hb C, like sheep Hb A and Hb C, have similar efficiencies in transporting oxygen
      to the tissues. As in other ruminant Hbs, the effect of temperature on the oxygen
      affinity is slight. Data suggest that mouflon Hb B is not only structurally, but
      even functionally, more similar to sheep Hb A than to sheep Hb B.

PMID- 9253180
TI  - Abundant synthesis of transthyretin in the brain, but not in the liver, of
      turtles.
AB  - The binding of thyroxine to proteins in the blood plasma of the turtle, Trachemys
      scripta, was analyzed by incubation with radioactive thyroxine, electrophoresis
      and autoradiography. Albumin and an alpha-globulin were found to bind thyroxine;
      no thyroxine-binding transthyretin was detected in the prealbumin region. In
      contrast to blood plasma, a thyroxine-binding prealbumin was observed in medium
      from T. scripta choroid plexus incubated in vitro. RNA was extracted from brain
      tissue containing choroid plexus and from liver of T. scripta and Chelydra
      serpentina and analyzed by hybridization with transthyretin cDNA from the lizard
      Tiliqua rugosa. The brain RNAs contained substantial amounts of transthyretin
      mRNA, whereas only trace amounts of transthyretin mRNA were detected in RNA from
      liver. No transthyretin mRNA was observed in RNA from kidney. The results support
      the hypothesis that the expression of the transthyretin gene first evolved in the
      choroid plexus of the brain at the stage of the stem reptiles, whereas abundant
      transthyretin synthesis in liver evolved much later, and independently, in
      mammals and birds.

PMID- 9253181
TI  - Metabolic response in skeletal muscle fibres of standardbred trotters after
      racing.
AB  - Histochemical and biochemical analyses were performed on muscle biopsies obtained
      after racing from the gluteus muscle of 18 standardbred trotters. Fibre type
      composition and enzyme activities varied among the horses. The percentage of type
      IIB fibres showed a positive correlation to the lactate dehydrogenase activity
      and a negative correlation to the citrate synthase activity. ATP concentrations
      in whole muscle after racing showed a negative correlation to both lactate and
      IMP concentrations. Within individual fibres, ATP concentrations varied markedly,
      with some type II fibres having values as low as 1-5 mmol/kg d.w. and some fibres
      having values as high as 40-58 mmol/kg d.w., whereas mean ATP concentration for
      whole muscle was 18.3 +/- 7.7 mmol/kg d.w. Some fibres with low ATP
      concentrations revealed high IMP concentrations. Blood samples taken after racing
      showed high values for lactate, ammonia, and uric acid in plasma. Muscle AMP and
      ADP concentrations after racing were related to the horses placing in a race,
      with higher concentrations giving a lower placing. The results of this study show
      that adenine nucleotide breakdown in muscle is of great importance for energy
      release during racing, and that ATP and IMP concentrations may very markedly
      among individual fibres. Thus, metabolite analyses on whole muscle must be
      evaluated with caution, as this only represents a mean value for metabolic
      responses in different fibres during racing.

PMID- 9253182
TI  - Characterization of phosphotyrosine phosphatase activity in sheep platelets:
      amphiphilic and hydrophilic forms.
AB  - Using O-phosphotyrosine as a substrate, we characterized the phosphotyrosine
      phosphatase (PTPase; protein-tyrosine-phosphate-phosphohydrolase, EC 3.1.3.48)
      activity from sheep platelets. PTPase was found to be located in three
      particulate subcellular fractions and in the cytosol, with K(m) values in the
      millimolar range. PTPase was strongly inhibited by vanadate, molybdate and HgCl2
      and only weakly inhibited by Zn2+. Other divalent cations and NaF had no
      significant effect on the activity associated with the membrane fraction but were
      slightly stimulatory as regards cytosolic activity. Heparin inhibited cytosolic
      activity 2-fold more than membrane-bound activity and dithiothreitol only
      inhibited cytosolic PTPase. Polycationic compounds were seen to be weak
      stimulators of all the PTPase activity. Solubilization of the PTPase from
      membranes always required a detergent. When subjected to Triton X-114 phase
      partitioning, PTPase was recovered in the detergent-rich (35%) and in the
      detergent-poor (65%) phases. Sedimentation analysis of the cytosolic PTPase
      showed a peak of 3.2S that remained unmodified when Triton X-100 or Brij 97
      sucrose gradients were used. Sedimentation analysis of the membrane-associated
      PTPase showed 6S and 3.7S peaks unchanged in Triton X-100 or Brij 97 gradients
      together with 7.5S and 10.3S shoulders that shifted to smaller sedimentation
      coefficients in Brij 97 sucrose gradients. These results support the view that
      sheep platelets contain amphiphilic and hydrophilic forms of PTPase.

PMID- 9253183
TI  - Miltpain, new cysteine proteinase from the milt of chum salmon, Oncorhynchus
      keta.
AB  - A new cysteine proteinase, salmon miltpain, was isolated and purified from the
      milt of chum salmon (Oncorhynchus keta). Native molecular mass was estimated as
      67,000 by gel filtration column chromatography (Shodex WS2003) and 22,300 by SDS
      polyacrylamide gel electrophoresis. Isoelectoric point was determined to be 3.9
      by isoelectric focusing. The first 15 amino acid residues in the N-terminal
      region were LPSFLY-AEMVGYNIL. The cysteine proteinase, which had a pH optimum of
      6.0 for Z-Arg-Arg-MCA hydrolysis, required a thiol-reducing reagent for
      activation and was inhibited by E-64, iodacetamide, CA-074 Me, TLCK, TPCK and
      ZPCK. The cysteine proteinase exhibited unique substrate specificity toward
      paired basic residues such as Lys-Arg, Arg-Arg at the subsites of P2-P1 and had a
      K(m) of 16.3 microM and kcat of 20.3 s-1 with Z-Arg-Arg-MCA as substrate and a
      K(m) of 52.9 microM and kcat of 1.79 s-1 with Z-Phe-Arg-MCA. This proteinase was
      found to considerably hydrolyze basic proteins such as histone, salmine and
      clupaine but not milk casein.

PMID- 9253184
TI  - Chromatographic and hyphenated methods for elemental speciation analysis in
      environmental media.
AB  - This review discusses chromatographic techniques that permit the analysis of
      speciated metals in the environment using conventional detectors, such as UV, and
      element-specific detectors, such as flame atomic absorption spectrometry,
      electrothermal atomic absorption spectrometry and inductively coupled plasma mass
      spectrometry. The importance of determining precise elemental forms in hazardous
      waste-contaminated soil, water and biota in terms of toxicity is outlined.
      Previous reviews on this subject are described and recent research on this
      subject is discussed. Most of the work cited has been performed in the 1990s and
      a table summarizing the chromatographic method and the detector system used,
      including brief comments on the work, is included to enable quick reference.

PMID- 9253185
TI  - Ion chromatographic characterization of toxic solutions: analysis and ion
      chemistry of biological liquids.
AB  - The literature on the analysis of biological fluids by ion chromatography is
      reviewed herein. It has been demonstrated that ion chromatography is the method
      of choice for the determination of anions such as chloride, nitrite, bromide,
      phosphate, nitrate, sulfate, oxalate, thiocyanate, thiosulfate, citrate,
      isocitrate, carbonate, and similar species. Cations such as sodium, ammonium,
      potassium, magnesium, and calcium in various biological solutions have also been
      successfully identified and quantified. The technique fulfils several
      requirements of a reliable microanalytical method by providing sufficient speed,
      automation, case of use, and accuracy. For many types of analyses, very little or
      even no sample preparation is required. Because of this, as presented in this
      review, ion chromatography is widely used not only to obtain reliable clinical
      data, but also to study ion chemistry. It has been an invaluable tool in
      nephrolithiasis and dental research. This review should provide a useful
      reference for analysts and researchers involved in clinical studies. The review
      is presented in four sections: (1) introduction, (2) methods of analysis, (3) ion
      chemistry and (4) critical comments and concluding remarks. Section 1, as usual,
      deals with the general introduction of the subject and objectives. Section 2
      includes the review of the literature on ion chromatography (IC) methods
      developed for routine analysis of various analytes present in biological fluids.
      Section 3 deals with the applications of IC used in the understanding of ion
      chemistry of biological fluids. Specifically, it deals with the physical
      chemistry aspects related to nephrolithiasis and dental research, such as
      speciation, driving force for crystals formation and crystallization, and
      pathophysiology. Section 4 contains critical comments and concluding remarks.

PMID- 9253186
TI  - Determination of coal tar and creosote constituents in the aquatic environment.
AB  - Creosote and its parent material, coal tar, are complex mixtures. Upon release
      their components fractionate into the air, water, soil/sediment and biota; as a
      function of their physical and chemical properties. Therefore, assessment of
      their fate and concentrations in the environment must consider a wide variety of
      both compounds and matrices. Analyses are typically complicated, consisting of
      sample extraction, purification and chromatography-based final characterization
      steps. Several new techniques have been introduced to reduce or simplify the
      number of steps, solvent and time required. Recently developed extraction methods
      include supercritical fluid, accelerated solvent, microwave and solid-phase
      microextraction. On-line purification and coupling of extraction and
      chromatography have also emerged. HPLC and GC remain the major tools for
      performing the final separations. Application of mass spectrometry has increased
      as more reliable, versatile and less expensive units have become available, such
      as the ion trap and mass selective detectors. Fluorescence and diode array UV, in
      concert with HPLC, and C-, S- and N-selective gas chromatographic detectors are
      also being applied.

PMID- 9253187
TI  - Gas chromatographic analysis of polychlorinated dibenzo-p-dioxins and
      dibenzofurans.
AB  - Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans are toxic
      compounds formed during natural processes and human activities. The extraction
      and clean-up for these compounds from various environmental and biological
      sources has been described. The gas chromatographic analysis of polychlorinated
      dibenzo dioxins/furans with different columns and detectors has been reviewed.
      The advantages of using a mass detector in the analysis are discussed.

PMID- 9253188
TI  - Methods for the determination of mutagenic heterocyclic amines and their
      applications in environmental analysis.
AB  - The environmental analysis of heterocyclic amines is important to preserve human
      health, because all these compounds are potent mutagens and many are carcinogens
      in experimental animals. This review summarizes the analytical methods for the
      determination of mutagenic heterocyclic amines and their applications to various
      environmental samples. High-performance liquid chromatographic methods with
      ultraviolet, electrochemical and fluorescence detections are commonly used for
      the quantification of heterocyclic amines. Moreover, liquid chromatography-mass
      spectrometry, gas chromatography, gas chromatography-mass spectrometry, capillary
      zone electrophoresis and enzyme-linked immunosorbent assay are also developed.
      Heterocyclic amines in complex environmental matrices are present at low parts
      per billion or less, so that the sample preparation influences the reliable and
      accurate analysis of these compounds. Mutagenic heterocyclic amines are widely
      distributed in a number of ambient environmental components such as airbone
      particles, diesel-exhaust particles, cigarette smoke, cooking fumes, rain water,
      sewage water, incineration-ash and soil. These facts suggest that mutagenic
      heterocyclic amines are likely to be ubiquitous environmental pollutants and
      humans are continually exposed to these compounds in normal daily life.

PMID- 9253189
TI  - Enantioselective determination of chiral organochlorine compounds in biota by gas
      chromatography on modified cyclodextrins.
AB  - Approaches to the gas chromatographic enantiomer separation of chiral
      organchlorines (alpha-hexachlorocyclohexane, cis- and trans-chlordane,
      heptachlor, heptachlorepoxide, oxychlordane, o,p'-DDT, compounds of technical
      toxaphene and stable atropisomeric polychlorinated biphenyls) are reviewed.
      Chiral stationary phases based on cyclodextrin derivatives and used for the gas
      chromatographic enantiomer separation of the chiral organochlorines are
      described. Enantiomeric ratios of chiral organochlorines in technical mixtures
      and biological samples are reported and discussed.

PMID- 9253190
TI  - Determination of polycyclic aromatic compounds and heavy metals in sludges from
      biological sewage treatment plants.
AB  - The procedure of the analysis of polycyclic aromatic hydrocarbons (PAHs) and
      their derivatives in the sludges from biological sewage treatment plants has been
      worked out. The analysis included isolation of organic matter from sludges,
      separation of the extract into fractions of similar chemical character,
      qualitative-quantitative analysis of individual PAHs and their nitrogenated and
      oxygenated derivatives. Liquid-solid chromatography, solid-phase extraction and
      semipreparative band thin-layer chromatography techniques were used for the
      separation. Capillary gas chromatography-mass spectrometry analysis of the
      separated fractions enabled identification of more than 21 PAHs, including
      hydrocarbons which contained 2-6 aromatic rings as well as their alkyl
      derivatives, 10 oxygen derivatives, 9 nitroarenes, aminoarenes and over 20
      azaarenes and carbazoles. Using the capillary gas chromatography-flame ionization
      detection technique the content of 17 dominant PAHs was determined. The content
      of heavy metals was determined in investigated sludges with the use of atomic
      absorption spectrometry. The concentrations of the respective metals could be
      ranked in the order Cd < Co < Ni < Pb < Cr < or = Cu < Mn < Zn < Fe. The sludges
      were analysed for the first time in Poland in view of their possible utilisation
      in agriculture and in cultivating dumps of coal mine wastes, taking into
      consideration the contents of toxic organic pollutants and heavy metals.

PMID- 9253191
TI  - Analysis of benzalkonium chloride in the effluent from European hospitals by
      solid-phase extraction and high-performance liquid chromatography with post
      column ion-pairing and fluorescence detection.
AB  - A highly reproducible and specific method for the analysis of the quaternary
      ammonium compound, benzalkonium chloride, in effluents from European hospitals is
      presented. Benzalkonium chloride was extracted with end-capped RP-18 solid-phase
      cartridges and was selectively eluted. The resulting solution was analyzed by
      high-performance liquid chromatography (HPLC). After elution from the analytical
      column of the HPLC system, 9,10-dimethoxyanthracene-2-sulfonate was added
      continuously as a fluorescence marker, forming a hydrophobic ion-pair with
      benzalkonium chloride. The ion-pair was analyzed by fluorescence detection. The
      method was applied to highly complex effluent samples from different sized
      European hospitals. The measured concentrations were between 0.05 and 6.03 mg/l.
      The amounts emitted per bed and year were 4.5-362 g and did not correlate with
      the size of the hospital. The total amounts were 2.6-909 kg/year.

PMID- 9253192
TI  - Analysis of toxic wastes in tissues from aquatic species. Applications of matrix
      solid-phase dispersion.
AB  - One of the difficult tasks in studying toxic wastes in the environment is the
      process involved in their extraction from biological matrices. This review
      addresses the regulatory aspects which mandate subsequent analyses in aquatic
      species and the studies which have addressed these problems from a variety of
      analytical perspectives. In this regard, the tissue extraction process known as
      matrix solid-phase dispersion is also reviewed and data are presented indicating
      that it may provide a generic process for the extraction and subsequent analysis
      of pesticides, polynuclear aromatic hydrocarbons and polychlorinated biphenyls.

PMID- 9253193
TI  - Analytical methods for the determination of organochlorine compounds. Application
      to environmental samples in the Slovak Republic.
AB  - The paper deals with the isolation of chlorinated phenols, benzenes and
      insecticides from water, soil and vegetable samples. A review of the current
      procedures is presented. Solid-phase extraction on Empore extraction discs was
      experimentally evaluated for isolation of the compounds from surface and ground
      waters. For the isolation of chlorophenols from soil and vegetable samples, a
      method of simultaneous steam distillation/extraction was elaborated which proved
      to be also applicable for waste waters and sludges. Chlorinated insecticides and
      benzenes were extracted from soil and vegetable samples with the Soxhlet
      procedure. Final determinations were carried out by GC-electron-capture
      detection. The recoveries of the methods were well over 70%, with relative
      standard deviations below 14%. Samples of surface and ground waters, soil and
      vegetables, mostly from the vicinity of chemical and municipal waste dumping
      sites, were analysed. The highest contamination levels were found for chlorinated
      phenols in surface water from the vicinity of a former chemical waste dumping
      place where the concentrations of 2,6-dichlorophenol and pentachlorophenol were
      4.3 and 3.9 micrograms l-1, respectively.

PMID- 9253195
TI  - Rigid porous polyacrylamide-based monolithic columns containing butyl
      methacrylate as a separation medium for the rapid hydrophobic interaction
      chromatography of proteins.
AB  - Macroporous poly(acrylamide-co-butyl methacrylate-co-N,N'-methylenebisacrylamide)
      monoliths containing up to 15% butyl methacrylate units have been prepared by
      direct polymerization within the confines of HPLC columns. The hydrodynamic and
      chromatographic properties of these 50 mm x 8 mm I.D. columns-such as back
      pressure at different flow-rates, effect of percentage of hydrophobic component
      in the polymerization mixture, effect of salt concentration on the retention of
      proteins, dynamic loading capacity, and recovery-were determined under conditions
      typical of hydrophobic interaction chromatography. Using the monolithic column,
      five proteins were easily separated within only 3 min.

PMID- 9253194
TI  - Speciation of organotin compounds in marine biomaterials after basic leaching in
      a non-focused microwave extractor equipped with pressurized vessels.
AB  - A rapid method for the speciation of butyl- and triphenyltin compounds in marine
      biotissues is described. A non-focused microwave extractor, operating at a power
      of 950 W and equipped with 12 pressurized vessels, was used to achieve fast
      sample leaching with tetramethylammonium hydroxide. The pH of the liquid extract
      was adjusted to 5. Organotins were ethylated with sodium tetraethylborate,
      extracted in isooctane and determined by means of a microwave-induced plasma
      atomic emission detector coupled to a gas chromatograph. The stability of butyl
      and phenyl compounds, exposed to the microwave energy, was studied as a function
      of the vessel temperature. The possibility of simultaneous carried-out
      extractions and the use of microwave to perform the ethylation and extraction of
      organotin compounds was also studied. The full procedure was validated with
      certified material NIES-11 and with real samples, by comparison with a classic
      leaching method using tetramethylammonium hydroxide without microwave.

PMID- 9253196
TI  - Liquid chromatography-electrospray mass spectrometry with in-source fragmentation
      for the identification and quantification of fourteen mutagenic amines in beef
      extracts.
AB  - Conditions for the liquid chromatography-electrospray mass spectrometric (LC-ES
      MS) determination of the fourteen most abundant heterocyclic amines and related
      compounds that can be produced in thermally processed foods were established. The
      simultaneous separation of all HAs on an octadecylsilane microbore column using a
      gradient elution with 5 mM ammonium acetate, pH 4.0, and acetonitrile was
      optimized. The mass spectra obtained at different extraction voltages were
      studied. The highest extraction voltages provided structural information for the
      characterization of these amines. Good detection limits comparable with those of
      LC and electrochemical detection were obtained. The method was applied to the
      analysis of these mutagens in beef extracts after a solid-phase extraction clean
      up and in-source fragmentation had been applied for confirmation purposes. The
      levels of several heterocyclic amines measured were estimated to be in the range
      of 7.8-135.2 ng g-1.

PMID- 9253197
TI  - Development and validation of a high-performance liquid chromatography method for
      the determination of cold relief ingredients in chewing gum.
AB  - An isocratic high-performance liquid chromatography (HPLC) method for the
      simultaneous determination of the active compounds paracetamol, pseudoephedrine
      and chlorpheniramine in chewing gum samples has been developed and validated. The
      method required a simple liquid-liquid extraction using n-hexane and a mixture of
      water-acetonitrile prior to HPLC analysis. The chromatographic separation was
      achieved with an aqueous solution containing hexylamine (pH 3)-acetonitrile as
      the mobile phase, a Spherisorb C18 column and UV detection at 220 nm. As an
      application, the proposed method has been used to evaluate the release into
      saliva of these compounds from samples under a controlled human chewing process.

PMID- 9253198
TI  - Role of PSO genes in the repair of photoinduced interstrand cross-links and
      photooxidative damage in the DNA of the yeast Saccharomyces cerevisiae.
AB  - Recent progress in elucidating the molecular structure of the PSSO genes PSO2 to
      PSO7 is presented. Their role in DNA repair and mutagenesis is discussed in the
      light of the putative proteins encoded in the respective ORFs and with the
      knowledge of recent progress in biological and biochemical experimentation. The
      role of the RecA protein in some steps of DNA repair in Saccharomyces cerevisiae
      is presented and discussed.

PMID- 9253200
TI  - In vitro and in vivo spectrofluorometry of a water-soluble meta
      (tetrahydroxyphenyl)chlorin (m-THPC) derivative.
AB  - The pharmacokinetics of a water-soluble derivative obtained from meta
      (tetrahydroxyphenyl)chlorin (m-THPC) was evaluated in in vitro and in vivo
      studies. Cytoplasm fluorescence was measured in two cell models (L1210 and HT29)
      using a flow cytometer and a confocal microspectrofluorometer. Cells were
      incubated with the compound at several doses (0-150 micrograms ml-1 for flow
      cytometry) and for several time periods (0-6 h for microspectrofluorometry). For
      in vivo studies, nude mice were grafted with human adenocarcinoma 15 days before
      intraperitoneal injection of polyethylene glycol-m-THPC (PEG-m-THPC).
      Fluorescence was recorded through an optical fibre spectrofluorometer using the
      660 nm peak for detection. In in vitro studies, the fluorescence was found to be
      proportional to the dose. Maximum fluorescence was recorded in L1210 cells
      earlier and more intensely than in HT29 cells (3 h at 202 +/- 14 counts s-1 and 5
      h at 43 +/- 2.15 counts s-1 respectively). Concerning in vivo studies, maximum
      tumour fluorescence was observed 24 h after injection (3568 +/- 178 counts s-1).
      Selectivity was expressed by the calculated tumour-to-skin and tumour-to-muscle
      ratios. The time taken to observe the maximum ratios (2.95 +/- 0.16 for tumour-to
      skin and 6.61 +/- 0.3 for tumour-to-muscle) was almost the same as the time taken
      to observe the maximum fluorescence in the tumour. Studies are in progress to
      correlate these results with photodynamic effects.

PMID- 9253199
TI  - A solubilization technique for photosensitizer quantification in ex vivo tissue
      samples.
AB  - The determination of the photosensitizer concentration in ex vivo tissue samples
      is commonly used for pharmacokinetic and dosimetric studies of photodynamic
      therapy, both clinically and pre-clinically. In this report, a new method is
      presented based on tissue solubilization and subsequent fluorometry. This method
      has the advantages of good sensitivity, accuracy and reproducibility, as well as
      low cost and ease of handling of the tissue samples. The method was tested for
      six different photosensitizers in a variety of tissues. The accuracy and
      concentration detection limits are compared with those of other published
      extraction methods.

PMID- 9253201
TI  - Photodynamic effects of meso-tetra (4-sulfonatophenyl)porphine on human leukemia
      cells HEL and HL60, human lymphocytes and bone marrow progenitor cells.
AB  - Meso-tetra(4-sulfonatophenyl)porphine (TPPS4), in combination with a light dose
      of 14 J cm-2, has a profound negative effect on the proliferation and viability
      of leukemia cells HL60 (human promyelocytic leukemia) and HEL (human
      erythroleukemia), the viability of normal lymphocytes and the colony-forming
      activity of human bone marrow progenitor cells. However, normal leukocytes
      (monocytes, granulocytes) are, to a large extent, resistant to photodynamic
      treatment (PDT). Whilst DNA fragmentation suggesting apoptosis is induced in HL60
      cells, accumulation in the interphase of the cell cycle (G0/G1, G2/M) is mainly
      operative in the TPPS4-mediated PDT of HEL cells. The "dark" effect of TPPS4 on
      the cell viability is below 15% up to a concentration of 40 microM.

PMID- 9253203
TI  - Comparative analysis of the metazoan parasite communities of leatherjackets,
      Oligoplites palometa, O. saurus, and O. saliens (Osteichthyes:Carangidae) from
      Sepetiba Bay, Rio de Janeiro, Brazil.
AB  - One hundred and fifty-seven specimens of leatherjackets, 84 specimens of
      Oligoplites palometa (Cuvier), 37 specimens of O. saurus (Bloch & Schneider), and
      36 specimens of O. saliens (Bloch) captured at the Sepetiba Bay, State of Rio de
      Janeiro, between March of 1991 and November of 1992, were necropsied to study
      their communities of metazoan parasites. All fishes studied were parasitized by
      one or more metazoan species. Eighteen parasite species were found in O. palometa
      and 13 parasite species were found in O. saurus and O. saliens, respectively. The
      digeneans were the majority of the parasite specimens collected, with 90.3%,
      82.2%, and 87.7% in O. palometa, O. saurus, and O. saliens, respectively. The
      Simpson index was lower than 0.25 for the 3 host species, showing an absence of
      concentration for dominance. The similarity coefficients among the parasite
      communities of the 3 fish species was above 66%. The parasites of the 3 host
      species showed typical overdispersed pattern of distribution. Four cases of
      positive correlation between host's total length and prevalence and parasite
      intensity were found. The majority of the species did not show influence of host
      sex. The 3 host species had similar parasite diversity, which was not correlated
      with the host's total body length and there was no significant difference between
      male and female hosts. Oligoplites palometa and O. saurus each had one pair of
      ectoparasite species sharing a positive association and with a positive
      correlation between their intensities. No pairs of associated species were found
      in O. saliens. Parasites were found along the entire extension of the
      gastrointestinal tract of the 3 host species. The parasite communities of O.
      palometa, O. saurus, and O. saliens are defined as isolationists because there
      are few evidences of interspecific association or covariation. The presence of
      larval stages of cestodes and nematodes suggests that the three species of
      Oligoplites are at an intermediate level in the marine trophic web.

PMID- 9253204
TI  - [Effect of fire on understory birds of a gallery forest in central Brazil].
AB  - Habitat burning may cause significant population and community changes in animals
      and plants, specially when the humans increase fire frequency. We mist-netted the
      understory birds of a gallery forest from the cerrado region of central Brazil
      before and after a fire of unknown cause which burned the Ecological Reserve of
      the University of Brasilia, Brasilia, DF, in September 1987. We conducted mist
      netting mostly during the morning, using 12 mist-nets distributed on 2.5 ha in
      the interior and border of the forest. We captured 137 individuals of 37 species,
      51 individuals of 21 species during 135.5 net/h before the fire, and 98
      individuals of 33 species during 233 net/h after the fire. The bird community as
      a whole did not change after the fire. The observed changes in the bird community
      were related to the type of habitat used by some species of birds than to their
      diet. Species typical to gallery forests are probably less adapted to habitat
      burning than species that occur in other habitats and may be suffering a decrease
      or a disturbance in their population structure, revealing an important problem of
      cerrado bird conservation.

PMID- 9253205
TI  - DNA fingerprinting in the rare black-fronted piping guan Pipile jacutinga
      (Cracidae, Aves).
AB  - Brazilian Cracidae are threatened by heavy environmental degradation and hunting.
      The Black-fronted piping-guan (Pipile jacutinga) used to inhabit the Atlantic
      coastal highland forests. Now it occurs in limited forest areas where it is
      rarely seen. Interative management, including captive breeding, might be an
      important action for its survival. We present data on DNA fingerprinting using
      Jeffreys' human minisatellite probes 33.6 and 33.15. Our results show that this
      technique is useful for estimating the genetic variability of natural populations
      and may help to maintain the genetic variability of captive bred individuals of
      this species. A linkage analysis of the fingerprint profiles in a family with 7
      chicks was performed (to estimate the number of independently segregating loci
      detected in this species) and at least 16 highly polymorphic independent loci
      were identified for each probe.

PMID- 9253202
TI  - Tumour-localizing and tumour-photosensitizing properties of zinc(II)-octapentyl
      phthalocyanine.
AB  - Zn(II)-octapentyl-phthalocyanine (ZnOPPc), incorporated into a Cremophor oil
      emulsion, was found to be a highly selective tumour-targeting agent (50-fold
      larger concentration in the tumour than in the peritumoral tissue) when injected
      at a dose of 1.46 mumol (kg body weight)-1 in Balb/c mice bearing an
      intramuscularly transplanted MS-2 fibrosarcoma. The pharmacokinetic properties of
      this phthalocyanine were closely similar to those found for the analogous
      octadecyl derivative, whereas the unsubstituted Zn(II)-phthalocyanine showed a
      lower efficiency and selectivity of tumour targeting than the octaalkyl
      substituted phthalocyanines. Irradiation of the ZnOPPc-loaded tumour with 620-700
      nm light 24 h after injection caused a significant delay of tumour growth with a
      gradual shrinkage of the neoplastic mass; the damage involved important
      contributions from both random necrosis and apoptosis of malignant cells.

PMID- 9253206
TI  - Chronic diffuse sclerosing osteomyelitis of the mandible or mandibular location
      of S.A.P.H.O. syndrome.
AB  - The chronic diffuse sclerosing osteomyelitis (CDSO) of the mandible has been
      described as an inflammatory disease characterized by recurrent episodes of
      intense pain in the mandible, often accompanied by trismus, paresthesia and
      progressive mandibular deformity. The etiopathogeny of this entity is not fully
      known. The differential diagnosis must be carried out very carefully, and the
      treatment results are very disappointing. Recently, evidence that suggests that
      CDSO may be the mandibular location of a more diffuse condition, the synovitis,
      acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome, has been offered. We
      describe two clinical cases of CDSO of typical evolution which fulfill the
      criteria for SAPHO syndrome, offering us an occasion for a review of the current
      literature.

PMID- 9253207
TI  - Antibacterial effects of amalgams on mutans streptococci in an in vitro biofilm
      test procedure.
AB  - Conflicting data continue to be presented in the literature regarding the
      antibacterial potential of various amalgam alloy compositions. The aim of the
      present study was to compare the antibacterial effects of 4 different amalgam
      samples on mutans streptococci using two in vitro test procedures. Glass and
      bovine enamel served as negative controls. The first test, one commonly used,
      consisted of immersing freshly prepared disks of the six materials in culture
      broth inoculated with mutans streptococci. Optical density measurements of the
      broth served to evaluate bacterial growth. This was followed by a biofilm
      technique which provided more intimate contact between the bacteria and specimen
      surfaces. With the exception of one high-copper lathe-cut amalgam, the first test
      revealed no antibacterial potential of the samples whereas the second test with
      the biofilm design elucidated significant differences in antibacterial potential
      between the amalgam alloy compositions and the controls. The biofilm technique,
      used in an in vitro test procedure, reflects the conditions of the oral
      environment more accurately than conventional test designs.

PMID- 9253208
TI  - The future of endoscopy.

PMID- 9253211
TI  - The story of nutrition.

PMID- 9253209
TI  - Determination of local tumour extension in cases of carcinoma of the prostate.
AB  - OBJECTIVE: Since most cases of carcinoma of the prostate (CaP) are still
      diagnosed at a time when the tumour has already spread beyond the prostatic
      capsula and therefore is incurable, recent impetus has been given to early
      detection with the chance of curative therapy. METHODS: This paper reviews of the
      literature concerning the ability of prostate-specific antigen (PSA), digital
      rectal examination (DRE), transrectal ultrasonography (TRUS), TRUS directed
      sextant biopsies, computerized tomography (CT) and magnetic resonance imaging
      (MRI) to determine the pathological stage of clinically organ-confined CaP.
      RESULTS: The combination of PSA, DRE, TRUS and TRUS directed sextant biopsies
      yield the best information about the pathological extent of clinically organ
      confined CaP. However, while this is true for a cohort of patients, the
      individual patient may still suffer from locally advanced disease that was
      unpredictable preoperatively by applying these tests. Positive surgical margins
      after radical prostatectomy are a logical consequence of advanced disease and
      therefore will be seen as long as no better clinical staging is available to the
      urologist and as long as CaP does not get diagnosed earlier in the course of the
      disease. CONCLUSION: At the present time the determination by PSA, DRE, TRUS and
      TRUS directed sextant biopsies are the diagnostic procedures of choice for the
      clinical staging of patients with potentially organ-confined CaP, CT and MRI are
      unable to markedly enhance the accuracy of clinical staging in this disease.

PMID- 9253212
TI  - Digital pulse volume recording: an essential test for the assessment of arteritis
      in diabetic patients.
AB  - The high incidence of medial calcification in the distal arteries of lower
      extremities in diabetic patients is responsible for most of the errors made in
      measuring ankle-pressure index. Because digital arteries are rarely calcified,
      digital pulse volume recording has been proposed as a specific and complementary
      test. Between March 1993 and March 1996, this test was performed in addition to
      ankle-pressure index in 66 diabetic patients. The ankle-arm index was
      overestimated and erroneous in 89.4% of cases. Digital arteries were calcified in
      74% of cases and diabetic neuropathy present in 53% of cases. Assessment of the
      severity of arteritis by digital pulse volume recording (category 1 to 5) has led
      to better prevention and treatment. It is an essential test for the assessment of
      arteritis in diabetics, but also for the prediction of success of a surgical
      procedure: distal amputation, lumbar sympathectomy and arterial reconstruction.

PMID- 9253213
TI  - Human leukocyte antigen frequencies in a selected group of Lebanese Greek
      Orthodox.
AB  - HLA classes I and II profiles were determined among 45 unrelated Lebanese Greek
      Orthodox by the complement dependent lymphomicrocytotoxicity assay. HLA epitope
      frequencies and alleles in linkage disequilibrium were determined; the obtained
      results were then compared to those reported for other groups. Moreover, possible
      HLA-disease associations were examined; medical history in relation to diabetes,
      rheumatoid arthritis, and ankylosing spondilitis was taken for each of the 45
      individuals. The results indicated that: 1) There were similarities and
      differences in HLA frequencies and alleles in linkage disequilibrium in Greek
      Orthodox as compared to those in other groups. It is worth mentioning the higher
      frequencies of B35, DR11, and DQ3 and the existence of linkage disequilibrium
      between DR11 and DR52 and DR4 and DR53 in Greek Orthodox. 2) Preliminary results
      indicate that there were no significant HLA-disease associations between each of
      DR4 and rheumatoid arthritis, DR4 and insulin dependent diabetes mellitus (IDDM),
      and B27 and ankylosing spondilitis in the group studied. Such associations have
      been reported in North American Caucasians.

PMID- 9253214
TI  - Nutrition in renal disease.

PMID- 9253215
TI  - Nutrition of infants and children during acute diarrhea.

PMID- 9253216
TI  - Setting the agenda for research and education on coronary heart disease.
AB  - Coronary heart disease (CHD) disproportionately affects the African American
      population with death and disability. The disparity in mortality continues to
      exist between the general population and African Americans despite decreases in
      death rates in both groups since the 1970s. The National Heart, Lung, and Blood
      Institute (NHLBI) is committed to developing and supporting research and
      activities that improve the health of African Americans through community
      partnership initiative. One such initiative is the CHD in Blacks Project,
      developed to increase awareness of the adverse effects of CHD, encourage healthy
      lifestyle behaviors, and, among health professionals, ensure that the latest
      treatment guidelines from the NHLBI in high blood pressure, high blood
      cholesterol, and obesity are used. The NHLBI has also established a network of
      health professionals from across the country to assist in developing medical
      education programs and community education outreach activities in conjunction
      with the National Medical Association, the Association of Black Cardiologists,
      and the National Black Nurses Association.

PMID- 9253217
TI  - Research in coronary heart disease in blacks: issues and challenges.
AB  - Research on coronary heart disease (CHD) has contributed to the decline in
      cardiovascular disease morbidity and mortality during the past three decades.
      However, life expectancy and rates of illness and death from CHD have not
      improved for blacks as for whites. Blacks have not experienced the full benefit
      of research advancements for a variety of reasons, including insufficient
      scientific data, lack of research focused on minority populations, and limited
      access to health care resources and technology. In order to address these
      disparities in prevention, diagnosis, treatment, and outcomes of CHD in blacks,
      the National Heart, Lung, and Blood Institute converted a Working Group on
      Research in Coronary Heart Disease in Blacks. In its deliberations, the working
      group identified 10 priority research areas, which are treatment, epidemiology
      (data collection and analysis), evaluation of chest pain and diagnosis of CHD,
      prevention and behavior, risk factors, genetics, vascular biology, left
      ventricular hypertrophy, coronary microvasculature, and sudden cardiac death.

PMID- 9253218
TI  - Cardiovascular disease in African American and white physicians: the Meharry
      Cohort and Meharry-Hopkins Cohort Studies.
AB  - Differences in cardiovascular disease (CVD) were studied in a cohort of medical
      students from the classes of 1958-65 of Meharry Medical College (n = 435), all
      African Americans, and the classes of 1957-64 of Johns Hopkins University (n =
      580), all white. At baseline, African Americans were older (27 vs. 24 years, p =
      0.001), more likely to smoke (71 vs. 47 percent), had greater body mass index (24
      vs. 23 kg/m), and had higher systolic blood pressure (120 vs. 116 mmHg). At
      follow-up (23-35 years later), African American physicians had higher CVD risk
      (RR = 1.65, 95% CI = 1.3-2.41), higher incidence of coronary artery disease (1.4
      times), and much higher case fatality (51.5 vs. 9.4 percent). Risk factor levels
      in youth can predict CVD events several years later; predictors may differ
      between racial groups. Best predictors were cigarette smoking, cholesterol, and
      paternal history in white physicians, and blood pressure in African American
      physicians.

PMID- 9253219
TI  - Diagnosis and therapeutic intervention in the management of coronary artery
      disease in African Americans.
AB  - Coronary artery disease (CAD) is the leading cause of death in African Americans,
      despite the lower prevalence of anatomic coronary atherosclerosis in this group.
      Risk factors for CAD in African Americans are considerable; however, the specific
      role of these risk factors in the excess mortality rates as compared with that of
      whites is not clarified. Factors such as differences in vascular pathobiology may
      be important in determining the cause of the excess mortality. The higher
      prevalence of normal coronary angiograms in African Americans with angina may be
      caused by pathobiology related to microvascular function and reserve. When access
      is available, the initial approach to diagnoses and management of coronary artery
      disease in African Americans is no different from that in other populations.
      Diagnostic approaches and therapeutic interventions are needed to identify the
      cause and modify the effects of the excess risks from coronary artery disease in
      African Americans.

PMID- 9253220
TI  - Stroke Belt initiative: the Tennessee experience.
AB  - African Americans have a higher rate of stroke than other U.S. population groups.
      As part of the 11-state "Stroke Belt" region, Tennessee has the fifth highest
      death rate from stroke in the country. In 1993, a two-year community-based
      project was initiated to reduce the incidence of stroke and its associated risk
      factors among African Americans. Three counties, Shelby (Memphis), Davidson
      (Nashville), and Hamilton (Chattanooga), were selected as project sites because
      of their large African American populations. Specific objectives of the project
      were to promote risk factor awareness in African Americans, assist African
      American churches and community groups in developing and implementing
      intervention programs, and build the capacity for intervention programs within
      African American communities by collaborating with a variety of community
      organizations. This article describes the program's approach, which included
      using both adults and youth as mentors. In addition, it presents major
      accomplishments and lessons learned in project implementation.

PMID- 9253221
TI  - Faith-based health needs assessment: implications for empowerment of the Faith
      community.
AB  - Churches are often caught in the middle of the struggle between health care
      institutions and managed care organizations. A faith-based center of excellence
      model is proposed that would establish a middle ground between the secular and
      "sacred" aspects of health care. Such a model would focus on using the faith
      community to influence the behavior and lifestyle of persons within the organized
      public health model, thus providing a new model of ministry. This process can
      increase an understanding of the tools needed for the clergy to be better
      caregivers, more influential co-change agents, and more informed about data
      driven outcome ministry. This integrated process is critical for real change in
      health outcomes, for the improvement of primary prevention, and for reducing
      disease mortality.

PMID- 9253222
TI  - Cardiovascular implications of smoking: the surgeon general's point of view.
AB  - One-fifth of all heart disease-related deaths are due to cigarette smoking.
      Smoking alone doubles the risk of heart failure. African Americans suffer the
      highest death rates from smoking among all U.S. population groups. Excess risk of
      heart disease caused by smoking can be reduced by half after just one year of
      quitting smoking. Therefore, the Agency for Health Care Policy and Research
      recommends that all patients who smoke be offered smoking cessation treatments
      such as nicotine replacement therapy, social supports, and skills training to
      achieve smoking abstinence. Such treatments should also include nutritional
      counseling and programs of appropriate physical activity. Other strategies to
      reduce the prevalence of smoking among youth include curtailing marketing efforts
      that glamorize smoking and strict enforcement of the minimum-age-of-sale laws.
      With proper nutrition, moderate physical activity, and the cessation of smoking,
      the risk factors associated with heart disease could be greatly reduced.

PMID- 9253224
TI  - Strategies for enhancing research and research training programs for African
      Americans: viewing barriers as opportunities.
AB  - Minorities have long been excluded from biomedical research programs, both as
      researchers and as study participants. One reason for the dearth of minority
      researchers is their lack of awareness that federal and private financial
      assistance programs exist on their behalf. To provide opportunities for
      minorities in biomedical research, minority institutions must be given expanded
      opportunities to participate in federally sponsored biomedical research programs.
      Thus both governmental and private agencies need to appraise minority research
      institutions of the kinds of assistance available and how to access funds. One
      means of disseminating such information would be to post it on the Internet.
      Minority institutions, for their part, must make basic research a priority and
      engage in mentorship programs that encourage minority precollege students to
      pursue careers in the sciences. Researchers can gain the trust of African
      Americans through outreach programs, which may lead to the greater inclusion of
      this population in clinical trials.

PMID- 9253225
TI  - Cardiovascular risk factor screening and intervention in African American adults.
AB  - The Cardiac Health and Rehabilitation program of St. Thomas Hospital in
      Nashville, Tennessee, has developed a project to assess the effectiveness of a
      community-based cardiovascular risk assessment and intervention program directed
      at African American adults. The specific aim of this program is to assess the
      feasibility of implementing a community-based cardiovascular disease risk factor
      reduction program directed at African American adults. Its ultimate goal is to be
      able to teach African American adults cost-efficient, simple methods of exercise,
      nutrition, and weight management; smoking cessation; and blood pressure control.
      The program is expected to raise the African American community's awareness of
      the importance of modifiable cardiovascular disease risk factors and their effect
      on cardiac morbidity and mortality. The program is also expected to be able to
      evaluate the success of cardiovascular disease risk factor intervention and
      patient satisfaction with the program.

PMID- 9253223
TI  - Forging alliances to meet future research and training needs.
AB  - There are countless challenges in meeting the future needs of the biomedical
      research community. In an era of flattened research budgets, the overarching
      concern has become how more can be done with less. One approach, still novel for
      the biomedical research community but proven successful for the commercial
      sector, is the establishment of strategic alliances. Among federal entities, the
      National Institutes of Health (NIH) and the Office of Research on Minority Health
      (ORMH) have as their goal the improvement of the health of the nation's
      minorities through support for alliances between academic research institutions.
      These partnerships serve to maximize an institution's opportunity for success,
      especially with regard to research and training. There are many different
      opportunities for institutions to establish partnerships, especially among
      minority institutions, and between minority and majority institutions. Features
      of successful alliances are described, working partnership models identified, and
      other opportunities explored.

PMID- 9253226
TI  - Public health in a managed care environment.
AB  - As the health care system moves in a new direction, toward managed care, the
      critical role of public health in society's efforts to mitigate illness and the
      realization of health become more apparent. Indeed, the public health problems of
      this era will not yield to simple solutions. They require a multitude of
      resources, both human and material, and a myriad of services derived from these
      resources. Public health's role is to serve as the government's presence in
      assessing health status, developing policy, evaluating the effectiveness of
      policy implementation, and assuring access to and quality of comprehensive health
      services. Increasingly, public health must coordinate a wide array of systems in
      both the private and public sectors to fulfill its purpose.

PMID- 9253227
TI  - The impact of obesity on hypertension management in African Americans.
AB  - Blood pressure is strongly related to body weight, and control of obesity is a
      critical component of hypertension prevention and control. Data from multicenter
      studies such as the Trials of Hypertension Prevention, the Trials of
      Antihypertensive Interventions and Management, and the Trial of Nonpharmacologic
      Interventions in the Elderly help to set aside previous questions about whether
      the association of obesity with hypertension applies to African Americans. Given
      the high prevalence of overweight among African Americans, especially women, the
      issue is not whether weight reduction should be a component of hypertension
      prevention and treatment but how to design and implement programs that will help
      overweight African American men and women achieve permanent weight loss. Modest
      weight losses can not only prevent or reverse blood pressure elevations but also
      have a favorable impact on obesity-related cardiovascular risk factors such as
      diabetes and hyperlipidemia.

PMID- 9253228
TI  - Lessons learned from the Healthy Heart Community Prevention Project in reaching
      the African American population.
AB  - The Healthy Heart Community Prevention Project (HHCPP) is an ongoing program of
      cardiovascular risk identification and modification in the African American
      community in New Orleans, Louisiana. The program targets low socioeconomic status
      African American populations, which continue to have higher rates of coronary
      heart disease, stroke, and overall cardiovascular mortality than the general
      population. Among the HHCPP's initiatives have been the use of barbershops and
      beauty salons as blood pressure screening sites. Church-based programs, in which
      ministers provide "healthy heart sermons," as well as screenings at sports
      events, where volunteers provide health advice, have proven to be successful
      aspects of the program. The HHCPP has also offered educational sessions to a
      broad cross-section of health professionals, including physicians as well as
      nurse practitioners and nutritionists. Future initiatives include the
      establishment of cholesterol screening programs.

PMID- 9253230
TI  - The political agenda of health care for African Americans.
AB  - Health care reform presents both challenges and opportunities for African
      Americans. On the one hand, reform could result in the closure of black medical
      institutions and fewer black physicians. On the other hand, reform gives African
      Americans an opportunity to bargain for available resources to gain equality in
      health care services. To this end, the Volunteer State Medical Association has
      been involved in state health care reform. Its goals are to resolve the current
      financial crisis at black medical institutions; to assist in the survival and
      development of local black managed care organizations; to assure that all
      licensed black physicians have continued access to patients; and to develop black
      owned health-related businesses. The association has formed the Tennessee
      Coalition for Quality Health Care, a group of African American politicians,
      physicians, educators, and health care administrators who can negotiate with
      state and federal officials in the issue of health care reform.

PMID- 9253229
TI  - New insights and interventions: churches uniting to reach the African American
      community with health information.
AB  - Effective church-based community health programs must take a holistic approach
      when dealing with health problems among African Americans. Such an approach
      emphasizes the relationship between the physiological, psychological, and
      spiritual selves. These programs must also ensure the complete involvement of
      clergy and church members, who can participate in programs by providing a certain
      level of skill, thereby engendering a sense of partnership in the process. Also
      necessary is an emphasis on healthy living instead of a fear of dying. Rather
      than framing health issues in mortality statistics, church-based programs need to
      stress ways to improve the quality of life, in keeping with the messages conveyed
      by the church. By taking these approaches, health organizations will find a
      religious community more willing to accept health messages.

PMID- 9253231
TI  - The role of managed care: the national and Tennessee experiences.
AB  - The United States is the only developed country with no national health care
      policy. What exists is a national health insurance system. The problem with this
      system arises when paying for health care for the poor, who often require the
      most expensive type of care for acute or episodic ailments. Managed care, though
      not a panacea, has the potential of providing the organization to effectively
      control costs and change the existing health care paradigm from one of fee-for
      service inpatient care to one of ambulatory care, home-based care, and physician
      office-based procedures. An example of a state-based initiative that has cut
      medical costs is Tennessee's TennCare. Under TennCare, approximately 1.2 million
      Tennesseans are covered, nearly 400,000 of whom were previously uninsured. Such
      programs, both state and national, must now look to including prevention and
      wellness care to effectively change the underlying epidemiology of illness among
      the poor.

PMID- 9253232
TI  - Study of the secretion of substance P, neurotensin and somatostatin in patients
      with cholelithiasis.
AB  - A comparative, case-control study on the pre- and postprandial release of three
      gastrointestinal peptides implicated in gallbladder motility has been carried out
      in humans in the attempt to determine their possible role in the pathogenesis of
      cholelithiasis. Fifty-seven adult patients (40 females and 17 males) with an
      ultrasound diagnosis of gallstones and 20 healthy subjects (9 females and 11
      males) without cholelithiasis or other digestive pathology were studied. Plasma
      substance P, neurotensin and somatostatin were measured by means of RIA-I125 in
      basal fasting conditions and 30, 60 and 90 minutes after the oral intake of a
      semiliquid mixed meal. The levels of secretion of each hormone were compared in
      patients and healthy controls on an overall basis and in terms of sex, age and
      body weight. We found a basal and postprandial hypersecretion of substance P in
      patients with gallstones when compared with controls. Individuals with
      cholelithiasis showed a moderate decrease in neurotensin secretion after the oral
      meal. Somatostatin release was unchanged. In conclusion, patients with gallstones
      may present a functional disorder in the secretion of gastrointestinal hormones
      involved in gallbladder motility.

PMID- 9253233
TI  - Endoscopic polypectomy in the treatment of colonic adenomas containing
      adenocarcinoma.
AB  - Fifty-seven adenomas containing adenocarcinoma were removed endoscopically from
      the colons of 56 patients (36 males and 20 females) with a mean age of 64.5
      years. The 13 polyps containing carcinoma in situ were satisfactorily treated by
      endoscopic resection. In 29 cases, the carcinoma had invaded the head, neck or
      stalk of the polyp. The outcome was good in every case, including one involving
      invasion of the resection margin. Follow-up or intraoperative studies disclosed
      the presence of residual lesion in only 4 patients out of 15 with submucosal
      invasion. All four had invaded resection margins and incomplete endoscopic
      excision. Endoscopic polypectomy is a suitable therapeutic option for most
      colonic adenomas containing a carcinoma provided a complete resection is achieved
      with wide resection margins, particularly in those cases in which the submucosa
      is not reached.

PMID- 9253234
TI  - Analysis of the predictive value of clinical data in patients with suspected
      colonic disease.
AB  - OBJECTIVE: To develop guidelines for predicting colonic disease on the basis of
      clinical parameters. EXPERIMENTAL DESIGN: A prospective study of the clinical
      data prior to colonoscopy. On the basis of the endoscopic findings, the patients
      were divided into three diagnostic groups: absence of significant disease,
      significant benign disease and malignant disease. The patient population was
      divided randomly into two subgroups. The clinical data from one of them was used
      to build a database which, using Bayes' theorem, was compared with the variables
      from the other subgroup to predict the diagnosis for each patient. PATIENTS: A
      total of 336 patients (170 males and 166 females; mean age: 58 years; range: 15
      to 87 years) were evaluated. RESULTS: When the endoscopic findings were grouped
      on the basis of their clinical importance, 211 patients (63%) belonged to the
      group without significant disease, 60 patients (18%) had significant benign
      disease and 65 (19%) presented a neoplastic disease. Of the 21 variables selected
      for use in the database, 6 showed statistically significant differences in terms
      of the absence or presence of malignant disease: age, absence of previous similar
      episodes, weight loss, rectal bleeding, lack of improvement and the presence of a
      mass on digital rectal examination. The predictive model differentiated patients
      with neoplasm from those without malignant disease, but was not capable of
      identifying differences among the latter. The model was useful for assessing the
      risk of malignant disease for each patient. CONCLUSIONS: The predictive model
      obtained is a useful tool for establishing the diagnosis and the priority in the
      performance of colonoscopy.

PMID- 9253235
TI  - Plasminogen in patients with liver cirrhosis.
AB  - BACKGROUND: We studied the plasminogen concentration in patients with alcoholic
      liver cirrhosis in order to assess its synthesis in the liver and establish
      correlations with other routine parameters such as the albumin level and
      prothrombin time. MATERIAL AND METHODS: Plasminogen was determined by radial
      immunodiffusion albumin by nephelometry and the prothrombin time by Quick's
      method. The study involved 40 healthy volunteers and 80 patients diagnosed as
      having alcoholic liver cirrhosis. Histopathological confirmation was achieved in
      56 patients, while in the remainder it was based on other instrumental methods
      and clinical and laboratory findings. RESULTS: The plasminogen level was lower in
      patients with liver cirrhosis (7.8 +/- 0.3 mg/dl) than in healthy controls (11.7
      +/- 0.6 mg/dl). According to the Child-Pugh classification, the concentration in
      class A was 9.0 +/- 0.3 mg/dl, in class B it was 7.3 +/- 0.4 mg/dl and in class C
      it was 6.1 +/- 0.2 mg/dl. The differences between the groups were statistically
      significant. CONCLUSION: The plasminogen level is of diagnostic value in the
      assessment of liver function and correlates well with the albumin concentration
      and the prothrombin time.

PMID- 9253236
TI  - Characterization of the epidemiological process of HIV infection using some
      immunological markers.
AB  - In an attempt to elucidate the causes which led to the high percentage of HIV
      infection in the infantile population in Romania, the paper deals with the study
      of the evolution of the infection process, in the 0-6 years age group; the
      process was separately studied in children from closed collectivities (5,318
      sera) and children living with their families (2,462). The study of the various
      patterns obtained with sera analysed by western-blot allowed of concluding that
      the massive spreading of the infection in both types of infantile population
      occurred in 1991-1992, the most intense process being reported in the 0-2 years
      age group (children from closed collectivities). The differences between the
      evolution of HIV infection epidemic in the above mentioned infantile populations
      and that noticed in adults are shown.

PMID- 9253237
TI  - Pre- and post-therapy blood lymphocyte levels in IgE-negative urticaria,
      associated with several parasitic or fungal diseases.
AB  - 115 patients with non-immune (IgE-negative) urticaria, related to parasitic
      (lambliasis, oxyuriasis, ascaridiasis) or fungal (candidiasis) associations were
      investigated-both before and one month after specific and antihistaminic therapy
      concerning different percentage levels of blood lymphocyte sets and subsets, by
      means of flow cytometry. Before therapy, three kinds of immune deficiency
      patients were obtained, one in lambliasis and oxyuriasis, the second in
      ascaridiasis, and the third in candidiasis, respectively. Clinical, biological
      and immunological recovering after therapy exhibited some differences related to
      the presumed non-allergic etiology, i.e. better in lambliasis and oxyuriasis and
      worse in ascaridiasis and candidiasis.

PMID- 9253238
TI  - Experimental study on estimating the immunogenic potency of diphtheria and/or
      tetanus toxoids in monovaccines and associated vaccines.
AB  - The results obtained using the "classical" active immunoprotection tests on
      guinea pigs, biometrically interpreted by the regression analysis in "PROBIT"
      systems revealed that the biopreparations of the Cantacuzino Institute meet the
      validity conditions related to the parallelism of the "slopes" enabling the
      calculation of ED50 and of the relative potencies against the reference
      preparations. The results also showed that the relative potencies of the
      biopreparations tested by the two methodologies were very close. The geometrical
      means and the geometrical standard deviations of the titrers obtained in mice
      pointed to the similarity of the values following inoculation of the Cantacuzino
      Institute preparations on the one hand and of the international reference
      preparation on the other.

PMID- 9253239
TI  - Antibiotic resistance study of invasive S.pneumoniae.
AB  - 121 invasive pneumococci isolated from meningitis, septicemia, pneumopathies and
      other clinical infections (osteo-arthritis, peritonitis, sinusitis, otilis,
      conjunctivitis, plagues) were screened for susceptibility to penicillin G (P),
      erythromycim (E), chloramphenicol (Cl), tetracycline (T), ceftriaxone (Cro), and
      sulfametoxazole trimethoprim (SxT) by diffusimetric method, by MICs to P and Cro
      by agar dilutions and E-test. 48.8% were penicillin resistant (MICs > 0.12
      microgram/ml), 22.7% being highly resistant (MICs 3-8 micrograms/ml). Any strain
      was resistant to P only, but patterns with P included were frequent (55.8%).
      Resistance to SxT was highest (monoresistance 25.6% as well as polyresistance
      69.8%). 72.9% were resistant strains to > or = 1 antibiotic with 12 patterns of
      resistance (1-5 antibiotics). All of the strains were susceptible to Cro (MICs
      0.003-0.5 microgram/ml). Resistance was closely correlated to serotypes
      6,9,14,19,23 to site of isolation and diagnosis. Pneumococci from meningitis were
      2-3 times more susceptible to P,E,Cl,T and SxT than the isolates from
      pneumopathies or other infections.

PMID- 9253240
TI  - George Zotta (1886-1942). An early concept of malaria stratification.

PMID- 9253241
TI  - Determining EDTA in blood.

PMID- 9253242
TI  - Analysis of proteins by direct-scanning infrared-MALDI mass spectrometry after 2D
      PAGE separation and electroblotting.
AB  - A novel approach is reported for the analysis and identification of proteins
      separated by 2D-PAGE with scanning infrared matrix-assisted laser
      desorption/ionization mass spectrometry (scanning IR-MALDI-MS). The proteins of
      human blood plasma were separated by 2D-PAGE, electroblotted onto PVDF membranes,
      incubated in matrix solution, and then scanned by IR-MALDI-MS. Mass contour plots
      of selected spots were obtained. Protein separation is shown to be conserved by
      comparison with silver-stained gels. The sensitivity for the protein detection is
      comparable if not better than that of silver-stained gels. Posttranslational
      modifications were identified by comparing the measured mass to the one
      calculated from the known DNA sequence. Adduct formation to unprotected cysteine
      residues during gel separation is demonstrated for selected proteins.

PMID- 9253243
TI  - Quantitative capillary electrophoresis/ion spray tandem mass spectrometry
      determination of EDTA in human plasma and urine.
AB  - A quantitative method has been developed for the determination of EDTA in human
      plasma and urine. The samples are prepared with automated anion-exchange solid
      phase extraction using 100 microL of human plasma. The extracts are analyzed by
      capillary electrophoresis/mass spectrometry using selected reaction monitoring in
      the negative ion mode. Large-volume injections (10% of the CE capillary volume)
      are used to improve the concentration level of detection via field-amplified
      sample injection. The first reported validation of a CE/MS/MS technique was
      carried out for this method. Using a 13C stable-label isotope for the internal
      standard, the lower level of detection and lower level of quantitation were
      determined to be 7.3 and 14.6 ng/mL EDTA in human plasma, respectively. The
      injection precision had a relative standard deviation (RSD) of 6.1%. The intra
      assay precision was less than 15% RSD. The intra-assay accuracy was less than +/-
      12% bias from the nominal concentration. The interassay precision was less than
      18% RSD and the interassay accuracy was less than +/- 9% bias from the nominal
      concentration.

PMID- 9253245
TI  - Quantification of biomolecules by external electrospray ionization Fourier
      transform mass spectrometry.
AB  - Fourier transform mass spectrometry (FTMS) is well-known for its capabilities in
      structural characterization of molecules. Recent developments in radio frequency
      excitation, linearized trapping, and accumulation of ions generated from external
      sources have improved the potential of FTMS for quantitative analysis. Here, a
      commercial external electrospray ionization FTMS, employing a linearized ion trap
      (the Infinity Cell) and an ion accumulation procedure in which ions are deflected
      off-axis and injected into the trap, is evaluated as an analytical method for
      quantifying amino acids, peptides, and proteins. Linear response over
      approximately 2-3 orders of magnitude is observed for singly-charged ions with
      low coefficients of variation (generally < 10%), and the calibration curves
      generated can be used to quantify structurally similar analytes with < 4%
      relative error, as shown here for quantification of leucine enkephalin from
      curves generated by methionine enkephalin. Similar precision is obtained for
      multiply-charged lysozyme, but over only 1.5 orders of magnitude. Some m/z
      discrimination is observed as a function of trap accumulation potential for a two
      component cytochrome c/lysozyme mixture. The results are promising because they
      suggest that quantification using liquid chromatography coupled to electrospray
      FTMS is possible.

PMID- 9253244
TI  - Protein digest analysis by pressurized capillary electrochromatography using an
      ion trap storage/reflectron time-of-flight mass detector.
AB  - Pressurized capillary electrochromatography (pCEC) has been coupled to an ion
      trap storage/reflectron time-of-flight mass spectrometer for the analysis of
      peptide mixtures and protein digests. Taking advantage of the electroosmotic
      flow, high separation efficiency has been achieved in pCEC due to a relatively
      flat flow profile and the use of smaller packing materials. A supplementary
      pressure was used in these experiments which suppressed bubble formation and also
      allowed the tuning of the elution of peptides using the electrical field. In this
      work, a fast separation of a six-peptide mixture has been successfully performed.
      Using columns only 6 cm long, a tryptic digest of bovine cytochrome c was fully
      separated in around 14 min by properly tuning the applied voltage and the
      supplementary pressure. In addition, relatively complex protein digests, such as
      a tryptic digest of chicken ovalbumin, were analyzed using this pCEC/MS system,
      and more than 20 peaks were resolved in the total ion current chromatogram within
      17 min. The use of an ion trap storage/reflectron time-of-flight mass
      spectrometer as an on-line detector further increased the resolving power of the
      pCEC by unambiguously identifying coeluting components. The nonscanning property
      of the time-of flight mass analyzer and the ion signal integration capability of
      the ion trap were successfully combined to provide rapid and sensitive full-mass
      range detection in these experiments.

PMID- 9253246
TI  - High-sensitivity detection and postsource decay of 2-aminopyridine-derivatized
      oligosaccharides with matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - The sensitivities of oligosaccharide derivatives in matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) were
      compared using two matrixes, 2,5-dihydroxybenzoic acid (DHBA) and alpha-cyano-4
      hydroxycinnamic acid (CHCA). For this purpose, maltopentaose was tagged with 2
      aminopyridine (PA), 4-aminobenzoic acid ethyl ester (ABEE), and trimethyl-(p
      aminophenyl)ammonium chloride (TMAPA). DHBA was more advantageous for enhancement
      than CHCA. Among the derivatives, the sensitivity with the PA-tagged
      maltopentaose showed a 100-fold improvement over the native one with DHBA as a
      matrix, while the oligesaccharide derivatized with ABEE and TMAPA gave 30- and 10
      fold increases in sensitivity over the underivatized one. To obtain structural
      information from these derivatized oligosaccharides, postsource decay (PSD)
      during flight in the field-free drift in MALDI-TOFMS was measured. Predictable
      and reproducible fragmentation patterns could be obtained in all cases.
      Furthermore, we found matrix-dependence fragmentation with the PA-labeled
      oligosaccharide. With CHCA, a simple spectrum ascribable to Y series ions was
      obtained. On the other hand, both B and Y series ions were clearly observed in
      the DHBA case. The results demonstrate the usefulness of derivatives for
      sensitive analysis of oligosaccharides with MALDI.

PMID- 9253247
TI  - Solvent microextraction as a speciation tool: determination of free progesterone
      in a protein solution.
AB  - A 1-microL drop of n-octane suspended from the tip of a microsyringe needle in
      500 mL of stirred aqueous solution is used to extract unbound progesterone in the
      presence of 1% (w/v) bovine serum albumin (BSA) for analysis by gas
      chromatography (GC). The observed extraction kinetics are in good agreement with
      a proposed convective-diffusive mass transfer model which accounts for diffusion
      of both free and bound species in the aqueous Nernst diffusion film adjacent to
      the interface. The equilibrium binding constant, which can be measured both at
      equilibrium and at nonequilibrium extraction times, is in good agreement with
      literature values. The very small phase ratio employed (i.e., 2 x 10(-6) mL of
      organic/mL of water) avoids perturbation of the aqueous solution equilibria.

PMID- 9253248
TI  - Coupling condensation nucleation light scattering detection with capillary
      electrophoresis using electrospray.
AB  - An improved method for coupling capillary electrophoresis (CE) with condensation
      nucleation light scattering detection (CNLSD) is described. The method employs an
      electrospray aerosol source followed by aerosol particle neutralization within a
      weak plasma established by a polonium-210 alpha emitter. Sensitive, universal
      detection of underivatized proteins, peptides, and amino acids is demonstrated.
      The system performance was significantly affected by the operational mode of the
      electrospray source, characterized by the physical appearance of the droplet at
      the end of the electrospray capillary. With a so-called pulsating mode,
      relatively low backgrounds were obtained with 10 mM ammonium acetate or 10 mM
      ammonium acetate/10 mM ammonia CE buffers using one diffusion screen, allowing
      detection of proteins at single microgram per milliliter levels and amino acids
      and peptides at submicrogram per milliliter levels. Linearity of response,
      expressed as peak height or peak area; mass limits of detection (LODs) for
      proteins, peptides, and amino acids at the picogram level, corresponding to
      femtomole levels of peptides and amino acids or subfemtomole levels of proteins;
      and better detectability compared to UV absorbance at 214 and 200 nm were
      demonstrated. The separation efficiencies obtained with the CE-electrospray-CNLSD
      system are much higher than those obtained for a previously reported pneumatic
      nebulizer-based system and in the range of approximately 20,000-160,000 plates/m
      using the pulsating electrospray mode. With careful adjustment of the
      electrospray voltage, a different operating mode, called the silver bullet mode,
      could be established for which higher signals, lower background and background
      noise, and higher separation efficiencies were observed compared to the pulsating
      mode. The lower background levels observed with the silver bullet mode eliminated
      the need for the use of a diffusion screen for background control with the buffer
      employed. With the silver bullet mode without a diffusion screen, linear response
      and LODs at the 15 ng/mL level, corresponding to subpicogram or 1-2 fmol levels
      of underivatized peptides and amino acids, and plate numbers in the range of
      65,000-220,000 plates/m were estimated.

PMID- 9253250
TI  - Voltammetric detection for capillary electrophoresis.
AB  - Several approaches to implementing amperometric detection for capillary
      electrophoresis have been reported. This report describes the development of a
      voltammetric detector for CE. The detector is designed to minimize distortion of
      the voltammetry due to ohmic potential drop. This was accomplished by using a
      cast Nafion detection cell at the end of the separation capillary. The cast
      Nafion detection cell provided a low-dead-volume, low-resistance cell that
      minimized ohmic potential drop and peak band broadening. The ability to detect
      the current due to oxidation of analytes superimposed on a large background
      current was also improved. A dynamic background subtraction scheme was used in
      which a second working electrode, positioned in the electrochemical cell but
      outside of the detection cell, was used to compensate for the background current
      in real time. The output of the compensating working electrode was subtracted
      from the output of the detecting working electrode prior to analog-to-digital
      conversion. Postexperimental digital background subtraction was also implemented.
      This approach provided optimal elimination of the background current with maximal
      detection of the analytical signal. The voltammetric detector developed produced
      high-quality voltammetric response of analytes with injected concentrations as
      low as 0.20 microM. The system was evaluated by obtaining CE voltammograms of a
      mixture of eight test phenolic acids.

PMID- 9253249
TI  - Improved chiral separations using a polymerized dipeptide anionic chiral
      surfactant in electrokinetic chromatography: separations of basic, acidic, and
      neutral racemates.
AB  - Two polymeric chiral anionic surfactants [poly(sodium N-undecylenyl-L-valine)
      (poly-L-SUV) and poly(sodium N-undecylenyl-L-valine-valine) (poly-L-SUVV)] are
      compared as pseudostationary phases for chiral separations of basic, acidic, and
      neutral enantiomers. Parameters such as pH, concentration and type of background
      electrolyte, concentration of polymerized chiral surfactants, and injection size
      were studied to investigate the migration behavior and optimize the chiral
      resolution of several racemic analytes. At equivalent monomer concentrations, the
      migration factors for cationic enantiomers were larger with poly-L-SUV than with
      poly-L-SUVV. In contrast, the reverse was true for anionic enantiomers. However,
      in both cases, chiral recognition was significantly enhanced with poly-L-SUVV as
      compared to that with poly-L-SUV. It is interesting to note that the separation
      selectivity and resolution of a neutral racemate were slightly better with the
      latter, but only at the expense of longer analysis time and lower efficiencies.

PMID- 9253251
TI  - Microscale epitope mapping by affinity capillary electrophoresis-mass
      spectrometry.
AB  - Using beta-endorphin as a model system, a new microscale solution-based approach
      for linear epitope mapping based on affinity capillary electrophoresis-mass
      spectrometry (ACE-MS) is demonstrated. Tryptic peptides are separated in a
      neutral coated capillary and monitored by ultraviolet absorbance and electrospray
      mass spectrometry. Then, following injection of the peptide digest mixture, anti
      beta-endorphin antibody is injected. The peptide, which binds to the antibody, is
      captured and disappears from its migration time. Following this subtraction
      screening procedure, the binding of the individually synthesized or isolated
      immunoreactive peptide is examined by the ACE-MS procedure to confirm that the
      epitope resides on the peptide. A series of truncated peptides can then be made
      and the precise epitope determined by ACE-MS. The method utilizes low femtomole
      amounts of antibody and peptide digest per run and is rapid and easily
      automatable.

PMID- 9253252
TI  - Visible diode laser-induced fluorescence detection of phenylacetic acid in plasma
      derivatized with Nile blue and using precolumn phase transfer catalysis.
AB  - This study reports the application of Nile blue (NB), a farred oxazine label, as
      a precolumn derivatization reagent for the measurement of free levels of
      phenylacetic acid (PAA) in plasma. The measurement of PAA in psychiatric
      populations is important because it provides a marker for 2-phenylethylamine
      (PEA), which has been implicated in the pathogenesis of schizophrenia and major
      depression. PAA was derivatized with NB through an amide linkage in the presence
      of 2-chloro-1-methylpyridinium iodide (carboxylic acid activator, CMP) and
      triethylamine (base catalyst, TEA), respectively. The formation of the NB-PAA
      derivative was confirmed using normal phase and reversed phase thin-layer
      chromatography, reversed phase liquid chromatography, and electrospray mass
      spectrometry. The formation of the NB-PAA derivative was optimized using a
      sequential single factor approach. The optimal conditions for the formation and
      chromatographic separation of the derivative were determined to be 8.0 nmol/mL
      NB, 390 nmol/mL CMP, 2 mumol/mL TEA, a reaction time of 45 min, and a reaction
      temperature of 25 degrees C. This derivatization scheme was performed in a phase
      transfer catalysis mode that enabled the simultaneous extraction,
      preconcentration, and derivatization of the analyte in a single step. The limit
      of derivatization of PAA was determined to be 1.0 x 10(-9) M in phosphate
      buffered saline, a PAA-free matrix. This derivatization was limited not by the
      kinetics of the reaction but by the chromatographic separation of the derivative
      from a side reaction product. The method was used to estimate endogenous free
      levels of PAA in human plasma samples. The levels of PAA in four sources of
      plasma were determined to be within 30-70 ng/mL using the method of standard
      addition and reflected levels that have been reported in the literature. The
      limit of detection of the derivative was determined to be 7.33 x 10(-11) M using
      a laboratory-constructed HPLC-VDLIF detector.

PMID- 9253253
TI  - Peptide separation in normal phase liquid chromatography.
AB  - A new method is established for separating peptides in normal phase liquid
      chromatography using TSK gel Amide-80, carbamoyl groups bonded to a silica gel
      matrix, and an acetonitrile-water solution containing 0.1% trifluoroacetic acid.
      Peptide retention time increased with acetonitrile concentration in the initial
      eluent. Hydrophilic peptides with no retention in a reversed phase column were
      retained and separated in the present method. Separation selectivities in the
      present and reversed phase methods differed significantly. Two-dimensional
      separation of protein digest using reversed and normal phases was conducted,
      taking advantage of the differences in selectivities. All peptides obtained from
      the digest could be separated completely. The present method is useful for
      separating peptide mixtures in conjunction with reversed phase liquid
      chromatography. Peptide recovery from the Amide-80 column exceeded 80%, as with
      the reversed phase column, and repeatability and reproducibility were
      satisfactory.

PMID- 9253254
TI  - An optical method for evaluating ion selectivity for calcium signaling pathways
      in the cell.
AB  - A method for evaluating a physiologically relevant ion selectivity of Ca2+
      signaling pathways in biological cells based on a Ca(2+)-dependent on/off switch
      for cellular processes via calmodulin (CaM) chemistry is described. CaM serves as
      a primary ion receptor for Ca2+ and a given CaM-binding peptide as a target for a
      CaM-Ca2+ complex. Upon accommodating four Ca2+ ions in its binding sites, CaM
      undergoes a conformational change to form a CaM-Ca(2+)-target peptide ternary
      complex. This Ca(2+)-induced selective binding of the Ca(2+)-CaM complex to the
      target peptide was monitored by a surface plasmon resonance (SPR) technique. As a
      target peptide, a 26-amino acid residue of M13 derived from skeletal muscle
      myosin light-chain kinase was used. The target peptide was covalently immobilized
      in the dextran matrix on top of gold, over which sample solutions containing Ca2+
      and CaM were injected in a flow system. Ca(2+)-dependent SPR signals were
      observed for Ca2+ concentrations from 3.2 x 10(-8) to 1.1 x 10(-5) M and it
      leveled off. The observed SPR signals were explained as due to an increase in the
      refractive indexes caused by a Ca2+ ion-switched protein/ peptide interaction,
      i.e., Ca2+ ion to CaM and subsequent additional binding of the thus formed
      complex with immobilized M13. No SPR signals were however, induced by Mg2+, K+,
      and Li+ at concentrations as high as 1.0 x 10(-1) M; these results and previous
      spectroscopic data taken together conclude that these ions do not induce
      CaM/peptide interaction. Large changes in SPR signals were observed with a Sr2+
      ion concentration over 5.1 x 10(-4) M; Sr2+ ion behaved in this case as a strong
      agonist toward the Ca(2+)-dependent on/off switch of CaM. The present system thus
      exhibited "physiologically more relevant" ion selectivity in that relevant metal
      ions could switch on the CaM/peptide or -protein interaction rather than merely
      be bound to CaM causing no further signal transduction. The potential use of this
      finding for more widely evaluating cation selectivity toward the Ca2+ signaling
      process was discussed.

PMID- 9253255
TI  - Calibration of micropipets using the bioluminescent protein aequorin.
AB  - A new method for calibrating micropipets and determining accurate injection
      volumes using a pressure-based injector has been developed. This method employs
      the bioluminescent protein aequorin and can be used to determine injection
      volumes as small as 3 pL. The calibration plots are linear over at least 3 orders
      of magnitude. In contrast to conventional micropipet calibration methods that
      employ fluorescent molecules, the present method produces small background
      signals.

PMID- 9253256
TI  - Preventing perinatal infections.

PMID- 9253257
TI  - Regulating the pharmaceutical industry.

PMID- 9253258
TI  - Misconduct in research: editors respond.

PMID- 9253259
TI  - User fees.

PMID- 9253261
TI  - More freedom for doctors to move within EU.

PMID- 9253260
TI  - When the next influenza pandemic comes.

PMID- 9253263
TI  - Pain is often misdiagnosed.

PMID- 9253264
TI  - Half of the world lives in "medieval" squalor.

PMID- 9253262
TI  - Patenting of genes moves one stage closer.

PMID- 9253265
TI  - US tobacco firms target Asia.

PMID- 9253266
TI  - Romania to change health system.

PMID- 9253268
TI  - Contribution of deaths related to alcohol use to socioeconomic variation in
      mortality: register based follow up study.
AB  - OBJECTIVE: To estimate the contribution of excessive alcohol use to socioeconomic
      variation in mortality among men and women in Finland. DESIGN: Register based
      follow up study. SUBJECTS: The population covered by the 1985 and 1990 censuses,
      aged > or = 20 in the follow up period 1987-93. MAIN OUTCOME MEASURES: Total
      mortality and alcohol related mortality from all causes, from diseases, and from
      accidents and violence according to socioeconomic position. The excess mortality
      among other classes compared with upper non-manual employees and differences in
      life expectancy between the classes were used to measure mortality differentials.
      RESULTS: Alcohol related mortality constituted 11% of all mortality among men
      aged > or = 20 and 2% among women and was higher among manual workers than among
      other classes. It accounted for 14% of the excess all cause mortality among
      manual workers over upper non-manual employees among men and 4% among women and
      for 24% and 9% of the differences in life expectancy, respectively. Half of the
      excess mortality from accidents and violence among male manual workers and 38%
      among female manual workers was accounted for by alcohol related deaths, whereas
      in diseases the role of alcohol was modest. The contribution of alcohol related
      deaths to relative mortality differentials weakened with age. CONCLUSIONS: Class
      differentials in alcohol related mortality are an important factor in the
      socioeconomic mortality differentials in Finland, especially among men, among
      younger age groups, and in mortality from accidents and violence.

PMID- 9253269
TI  - Effect of cleansing the birth canal with antiseptic solution on maternal and
      newborn morbidity and mortality in Malawi: clinical trial.
AB  - OBJECTIVE: To determine if cleansing the birth canal with an antiseptic at
      delivery reduces infections in mothers and babies postnatally. DESIGN: Clinical
      trial; two months of no intervention were followed by three months of
      intervention and a final month of no intervention. SETTING: Queen Elizabeth
      Central Hospital (tertiary care urban hospital), Blantyre, Malawi. SUBJECTS: A
      total of 6965 women giving birth in a six month period and their 7160 babies.
      INTERVENTION: Manual wipe of the maternal birth canal with a 0.25% chlorhexidine
      solution at every vaginal examination before delivery. Babies born during the
      intervention were also wiped with chlorhexidine. MAIN OUTCOME MEASURES: Effects
      of the intervention on neonatal and maternal morbidity and mortality. RESULTS:
      3635 women giving birth to 3743 babies were enrolled in the intervention phase
      and 3330 women giving birth to 3417 babies were enrolled in the non-intervention
      phase. There were no adverse reactions related to the intervention among the
      mothers or their children. Among infants born in the intervention phase, overall
      neonatal admissions were reduced (634/3743 (16.9%) v 661/3417 (19.3%), P < 0.01),
      as were admissions for neonatal sepsis (7.8 v 17.9 per 1000 live births, P <
      0.0002), overall neonatal mortality (28.6 v 36.9 per 1000 live births, P < 0.06),
      and mortality due to infectious causes (2.4 v 7.3 per 1000 live births, P <
      0.005). Among mothers receiving the intervention, admissions related to delivery
      were reduced (29.4 v 40.2 per 1000 deliveries, P < 0.02), as were admissions due
      to postpartum infections (1.7 v 5.1 per 1000 deliveries, P = 0.02) and duration
      of hospitalisation (Wilcoxon P = 0.008). CONCLUSIONS: Cleansing the birth canal
      with chlorhexidine reduced early neonatal and maternal postpartum infectious
      problems. The safety, simplicity, and low cost of the procedure suggest that it
      should be considered as standard care to lower infant and maternal morbidity and
      mortality.

PMID- 9253270
TI  - Bone density and risk of hip fracture in men and women: cross sectional analysis.
AB  - OBJECTIVE: To determine the relative contribution of decline in bone density to
      the increase in risk of hip fracture with age in men and women. DESIGN: Incidence
      data of hip fracture from the general population were combined with the bone
      density distribution in a sample from the same population and with a risk
      estimate of low bone density known from literature. SETTING: The Netherlands.
      SUBJECTS: All people with a hospital admission for a hip fracture in 1993, and
      bone density measured in a sample of 581.4 men and women aged 55 years and over
      in a district of Rotterdam. MAIN OUTCOME MEASURE: One year cumulative risk of hip
      fracture by age, sex, and bone density measured at the femoral neck. RESULTS: A
      quarter of all hip fractures occurred in men. Men reached the same incidence as
      women at five years older. Controlled for age, the risk of hip fracture by bone
      density was similar in men and women. The risk of hip fracture increased 13-fold
      from age 60 to 80; decrease in bone density associated with age contributed 1.9
      (95% confidence interval 1.5 to 2.4) in women and 1.6 (1.3 to 1.8) in men.
      CONCLUSIONS: The risk of hip fracture by age and bone density is similar in men
      and women. The decrease in bone density associated with age makes a limited
      contribution to the exponential increase of the risk of hip fracture with age.

PMID- 9253272
TI  - New connections between medical knowledge and patient care.

PMID- 9253271
TI  - Comparison of two methods of screening for genital chlamydial infection in women
      attending in general practice: cross sectional survey.
AB  - OBJECTIVES: To estimate the prevalence of Chlamydia trachomatis in asymptomatic
      women attending general practice: to assess the potential of the ligase chain
      reaction as a screening tool; and to evaluate selective screening criteria.
      DESIGN: Cross sectional survey. SETTING: Four general practices in northeast
      London. SUBJECTS: 890 women aged 18-35 years attending general practice for a
      cervical smear or a "young well woman" check between October 1994 and January
      1996. The women were tested for C trachomatis with confirmed enzyme immunoassay
      (endocervical specimens) and ligase chain reaction assay on urine specimens. MAIN
      OUTCOME MEASURES: Prevalence of C trachomatis infection in women aged 18-35 on
      the basis of each test; sensitivity and specificity of both tests in this
      population. RESULTS: Prevalence of confirmed infection was 2.6% (95% confidence
      interval 1.6% to 3.6%) in all women. Prevalence on the basis of enzyme
      immunoassay was 1.6% (0.8% to 2.7%), with a sensitivity of 60% and a specificity
      of 100%. Prevalence on the basis of ligase chain reaction was 2.5% (1.5% to
      3.9%), with 90% sensitivity and 99.8% specificity. Screening all women aged < or
      = 25 and all women who had had two or more partners in the past year would have
      detected 87% (20/23) of infections. CONCLUSION: Ligase chain reaction on urine
      samples performs at least as well as enzyme immunoassay on cervical specimens in
      this low prevalence population. It offers potential as a non-invasive screening
      tool. A simple selective screening strategy might be appropriate and would be
      able to detect most cases of infection. However, a rigorous economic evaluation
      of possible screening strategies is needed first.

PMID- 9253273
TI  - Science, medicine, and the future. Treatment of rheumatoid arthritis.

PMID- 9253274
TI  - ABC of mental health. Psychosexual problems.

PMID- 9253275
TI  - How to read a paper. Getting your bearings (deciding what the paper is about).

PMID- 9253276
TI  - Informed consent. The central problem is often poor design and conduct of trials.

PMID- 9253278
TI  - Informed consent. Other societies have different concepts of autonomy.

PMID- 9253277
TI  - Informed consent. Journals should require routine reporting of consent rates.

PMID- 9253279
TI  - Informed consent. British institutions collaborating in projects overseas may
      face dilemma.

PMID- 9253280
TI  - Informed consent. Research studies in diving medicine are considered by Ministry
      of Defence research ethics committee.

PMID- 9253281
TI  - Informed consent. Subjects may not understand concept of clinical trials.

PMID- 9253282
TI  - Informed consent. Informed consent is not always obtained in United States.

PMID- 9253283
TI  - Informed consent. Research in pregnancy brings special considerations.

PMID- 9253284
TI  - Informed consent. Explicit guidance is required on valid exemptions for need for
      ethical review.

PMID- 9253285
TI  - Informed consent. Lack of respect for patients in medical research may reflect
      wider disrespect in clinical practice.

PMID- 9253286
TI  - Informed consent. Rigorous studies are needed to determine values of
      interventions.

PMID- 9253287
TI  - Informed consent. Trials that use Zelen's procedure should be acceptable.

PMID- 9253288
TI  - Informed consent. Not seeking informed consent breaches patient's charter.

PMID- 9253289
TI  - Informed consent. Ethical principles may need to be adapted when research subject
      is not an individual subject.

PMID- 9253290
TI  - Informed consent. Study in which patients had HIV tests could have been designed
      differently.

PMID- 9253291
TI  - Informed consent. Informed consent is light years away for black African
      patients.

PMID- 9253292
TI  - Informed consent. Research suffers if patients suspect that their rights may be
      breached.

PMID- 9253293
TI  - Informed consent. Patients' knowledge that they are participating in trial may
      not bias results.

PMID- 9253294
TI  - Informed consent. Two stage randomisation and consent would overcome many
      problems.

PMID- 9253295
TI  - Informed consent. Ability to be informed is separate from ability to give
      consent.

PMID- 9253296
TI  - Informed consent. "Blanket" consent to trials would be a good idea.

PMID- 9253297
TI  - Informed consent. Respect for autonomy may conflict with principle of
      beneficence.

PMID- 9253299
TI  - French committee will investigate proposed link between activities of nuclear
      reprocessing plant and leukaemia.

PMID- 9253300
TI  - Plans are needed on how to cope with demand for ventilation during pandemic
      influenza.

PMID- 9253301
TI  - Scientists should inform public of risks of transgenic experimentation.

PMID- 9253302
TI  - Public should know of efficacy of early hospital treatment of paracetamol
      overdose.

PMID- 9253303
TI  - Balance in long-term follow up between secondary and primary care is necessary.

PMID- 9253304
TI  - Surgical management of pituitary tumors.

PMID- 9253305
TI  - Long-term effect of testosterone therapy on bone mineral density in hypogonadal
      men.
AB  - In both men and women, a decrease in bone mineral density (BMD) is a major
      symptom of hypogonadism. Although the effects of estrogens on osteoporosis in
      women are well documented, comparatively little is known about the effects of
      long term testosterone substitution on BMD in hypogonadal men. Therefore, we
      studied BMD in 72 hypogonadal patients (37 men with primary and 35 men with
      secondary hypogonadism) under testosterone substitution therapy that continued
      for up to 16 yr. Thirty-two of these men were also seen before initiation of
      therapy. At annual intervals, trabecular BMD of the lumbar spine was measured by
      quantitative computed tomography, a true volumetric and reproducible method for
      long term serial BMD measurements. Serum levels of testosterone increased to the
      normal range in all androgen-treated hypogonadal men. The most significant
      increase in BMD was seen during the first year of testosterone treatment in
      previously untreated patients, when BMD increased from 95.2 +/- 5.9 to 120.0 +/-
      6.1 mg/cm3 hydroxyapatite (mean +/- SE). Long term testosterone treatment
      maintained BMD in the age-dependent reference range in all 72 hypogonadal men,
      independent of the type of hypogonadism. Transdermal testosterone patches applied
      to the scrotum were as effective in normalizing BMD as im testosterone enanthate
      injections. In summary, testosterone therapy increases BMD in hypogonadal men
      regardless of age. The greatest increase is seen during the first year of
      treatment in previously untreated patients with low initial BMD. In hypogonadal
      men, BMD can be normalized and maintained in the normal range by continuous, long
      term testosterone substitution.

PMID- 9253306
TI  - Troglitazone ameliorates insulin resistance in patients with Werner's syndrome.
AB  - Insulin resistance in Werner's syndrome (WS) is probably due to defective
      signaling distal to the insulin receptor. To analyze the metabolic effects of
      troglitazone (TRO) in these patients, we performed frequently sampled iv glucose
      tolerance tests. Glucose kinetics were analyzed by the minimal model. Five
      patients with WS (mean age, 41.2 yr; body mass index, 17.0 kg/m2) were treated
      with TRO (400 mg/day) for 4 weeks. Each subject underwent a 75-g OGTT and
      frequently sampled iv glucose tolerance tests. Treatment reduced the area under
      the curve of glucose and insulin in the OGTT by 26% and 43%, respectively.
      Glucose tolerance, as manifested by the glucose disappearance rate improved
      significantly (1.36 +/- 0.16 to 1.94 +/- 0.30%/min; P < 0.05). Although the first
      phase insulin secretion was unchanged, insulin sensitivity and glucose
      effectiveness increased significantly [0.47 +/- 0.11 to 1.38 +/- 0.37 x 10(-4)
      min/pmol.L (P < 0.05) and 1.72 +/- 0.17 to 2.52 +/- 0.24 x 10(-2) min-1 (P <
      0.05), respectively]. However, treatment did not change glucose effectiveness at
      zero insulin. In patients with WS, TRO ameliorates glucose intolerance mediated
      by increased insulin sensitivity as well as glucose effectiveness, as assessed by
      minimal model analysis. TRO may modulate the postreceptor signaling component and
      be a clinically useful regimen for the treatment of patients with the
      intracellular insulin signaling defect.

PMID- 9253307
TI  - Marked decline in serum concentrations of adrenal C19 sex steroid precursors and
      conjugated androgen metabolites during aging.
AB  - The present data show a dramatic decline in the circulating levels of
      dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androst-5-ene-3 beta,17
      beta-diol (5-diol), 5-diol-sulfate, 5-diol-fatty acid esters, and androstenedione
      in both men and women between the ages of 20-80 yr. In the 50- to 60-yr-old
      group, serum DHEA decreased by 74% and 70% from its peak values in 20- to 30-yr
      old men and women, respectively. the serum concentrations of the conjugated
      metabolites of dihydrotestosterone (DHT), namely androsterone (ADT)-G, androstane
      3 alpha,17 beta-diol (3 alpha-diol-G), androstane-3 beta,17 beta-diol (3 beta
      diol-G), and ADT-sulfate are the most reliable parameters of the total androgen
      pool in both men and women, whereas serum testosterone and DHT can be used as
      markers of testicular secretion in men and interstitial ovarian secretion in
      women. The serum concentration of these various conjugated androgen metabolites
      decreased by 40.8% to 72.8% between the 20- to 30-yr-old and 70- to 80-yr-old age
      groups in men and women, respectively, thus suggesting a parallel decrease in the
      total androgen pool with age. As estimated by measurement of the circulating
      levels of these conjugated metabolites of DHT, it is noteworthy that women
      produce approximately 66% of the total androgens found in men. In women, most of
      these androgens originate from the transformation of DHEA and DHEA-S into
      testosterone and DHT in peripheral intracrine tissues, whereas in men the testes
      and DHEA and DHEA-S provide approximately equal amounts of androgens at the age
      of 50-60 yr. An additional potentially highly significant observation is that the
      majority of the marked decline in circulating adrenal C19 steroids and their
      resulting androgen metabolites takes place between the age groups of 20- to 30-yr
      olds and 50- to 60-yr-olds, with smaller changes are observed after the age of 60
      yr.

PMID- 9253308
TI  - Physiological changes in dehydroepiandrosterone are not reflected by serum levels
      of active androgens and estrogens but of their metabolites: intracrinology.
AB  - This study analyzes in detail the serum concentration of the active androgens and
      estrogens, as well as a series of free and conjugated forms of their precursors
      and metabolites, after daily application for 2 weeks of 10 mL 20%
      dehydroepiandrosterone (DHEA) solution on the skin to avoid first passage through
      the liver. In men, DHEA administration caused 175%, 90%, 200% and 120% increases
      in the circulating levels of DHEA and its sulfate (DHEA-S), DHEA-fatty acid
      esters, and androst-5-ene-3 beta,17 beta-diol, respectively, with a return to
      basal values 7 days after cessation of the 14-day treatment. Serum
      androstenedione increased by approximately 80%, whereas serum testosterone and
      dihydrotestosterone (DHT) remained unchanged. In parallel with the changes in
      serum DHEA, the concentrations of the conjugated metabolites of DHT, namely
      androsterone glucuronide, androstane-3 alpha,17 beta-diol-G, and androstane-3
      beta,17 beta-diol-G increased by about 75%, 50%, and 75%, respectively, whereas
      androsterone-sulfate increased 115%. No consistent change was observed in serum
      estrone (E1) or estradiol (E2) in men receiving DHEA, whereas serum E1-sulfate
      and E2-sulfate were slightly and inconsistently increased by about 20%, and serum
      cortisol and aldosterone concentrations were unaffected by DHEA administration.
      Almost superimposable results were obtained in women for most steroids except
      testosterone, which was about 50% increased during DHEA treatment. This increase
      corresponded to about 0.8 nM testosterone, an effect undetectable in men because
      they already have much higher (approximately 15 nM) basal testosterone levels. In
      women, the serum levels of the conjugated metabolites of DHT, namely androsterone
      glucuronide, androstane-3 alpha,17 beta-diol-G, androstane-3 beta,17 beta-diol-G,
      and androsterone-sulfate were increased by 125%, 140%, 120% and 150%,
      respectively. The present study demonstrates that the serum concentrations of
      testosterone, DHT, E1, and E2 are poor indicators of total androgenic and
      estrogenic activity. However, the esterified metabolites of DHT appear as
      reliable markers of the total androgen pool, because they directly reflect the
      intracrine formation of androgens in the tissues possessing the steroidogenic
      enzymes required to transform the inactive precursors DHEA and DHEA-S into DHT.
      As well demonstrated in women, who synthesize almost all their androgens from
      DHEA and DHEA-S, supplementation with physiological amounts of exogeneous DHEA
      permits the biosynthesis of androgens limited to the appropriate target tissues
      without leakage of significant amounts of active androgens into the circulation.
      This local or intracrine biosynthesis and action of androgens eliminates the
      inappropriate exposure of other tissues to androgens and thus minimizes the risks
      of undesirable masculinizing or other androgen-related side effects of DHEA.

PMID- 9253309
TI  - Medical therapy of Graves' disease: does thyroxine prevent recurrence of
      hyperthyroidism?
AB  - Sixty patients with Graves' disease (GD) hyperthyroidism were distributed in two
      randomized groups. Patients in group A (n = 30) received carbimazole by a
      titration regimen, and patients in group B (n = 30) were treated with higher
      doses of carbimazole plus T4. Clinical and analytical evaluations were done at
      baseline, during treatment (18.4 +/- 2.6 months), and after, until the relapse of
      hyperthyroidism, or for 4.98 +/- 1.6 yr in patients who did not relapse. There
      were no differences in clinical parameters, thyroid hormones, or TSH binding
      inhibitory immunoglobulins (TBII) levels between the two groups, either at
      baseline or at the end of treatment. Serum TSH persisted undetectable in 16 out
      of 60 patients (group A: 9; group B: 7), after treatment. Relapse occurred in 38
      patients (63.3%), (group A: 18 (60%) vs. group B: 20 (66.7%)). Patients who
      relapsed had bigger goiters at baseline (P = 0.02) and at the end of treatment (P
      = 0.03). Eighty-seven percent (14/16) of patients with undetectable TSH after
      therapy relapsed, vs. 54.5% (24/44) of those with normal TSH (P = 0.01).
      Undetectable TSH at the end of treatment was the only independent variable in the
      logistic analysis to predict relapse. Treatment modality did not influence the
      relapse rate. This study has found that, in Spanish patients, the use of high
      doses of carbimazole with T4 offers no advantages in the treatment of GD
      hyperthyroidism.

PMID- 9253310
TI  - Abnormal adrenal and vascular responses to vasopressin mediated by a V1
      vasopressin receptor in a patient with adrenocorticotropin-independent
      macronodular adrenal hyperplasia, Cushing's syndrome, and orthostatic
      hypotension.
AB  - The elucidation of gastric inhibitory polypeptide-dependent Cushing's syndrome
      suggested that ectopic expression or increased responsiveness of other adrenal
      hormone receptors may underlie ACTH-independent macronodular adrenal hyperplasia
      (AIMAH) or adrenocortical tumors. We studied a 36-yr-old woman with Cushing's
      syndrome, AIMAH, and orthostatic hypotension. During upright posture, cortisol
      and aldosterone were stimulated despite suppression of ACTH and renin. Arginine
      vasopressin (AVP, 10 U im), under dexamethasone suppression, increased plasma
      cortisol (3.4-fold), aldosterone (67-fold), and androgens in this patient but not
      in controls. ACTH 1-24, but not desmopressin acetate, angiotensin II,
      isoproterenol, or other hormones stimulated steroidogenesis in vivo. Plasma AVP
      was undetectable initially and increased suboptimally during posture tests after
      bilateral adrenalectomy. AVP stimulated cortisol production more in dispersed
      cells from the AIMAH than from a normal adult adrenal (424 vs. 135% at 10
      nmol/L). Adrenal V1-AVP receptor presence and mediation of response were shown by
      RT-PCR and by binding and [Ca+2]i studies. Post adrenalectomy, orthostatic
      hypotension persisted; a prolonged vasoconstrictive response to AVP was found in
      vitro in the patient's sc small arteries. We propose that altered adrenal and
      vascular responses of the V1-AVP receptor-effector pathway underlie this new
      syndrome.

PMID- 9253311
TI  - Changes in bone mineral density, body composition, and lipid metabolism during
      growth hormone (GH) treatment in children with GH deficiency.
AB  - Adults with childhood onset GH deficiency (GHD) have reduced bone mass, increased
      fat mass, and disorders of lipid metabolism. The aim of the present study was to
      evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid
      metabolism in GHD children before and during 2-3 yr of GH treatment (GHRx). Forty
      children with GHD, mean age 7.9 yr, participated in the study of bone metabolism
      and body composition; and an additional group of 17 GHD children, in the study of
      lipid metabolism. Lumbar spine BMD, total body BMD, and body composition were
      measured with dual-energy x-ray absorptiometry. Volumetric BMD (bone mineral
      apparent density, BMAD) was calculated to correct for bone size. BMD, BMAD, lean
      tissue mass, bone mineral content, fat mass, and percentage body fat were
      expressed as SD scores (SDS), in comparison with normative data of the same
      population. Lumbar spine BMD and BMAD and total body BMD were all decreased at
      baseline. All BMD variables increased significantly during GHRx, lumbar spine BMD
      SDS, already after 6 months of treatment. Lean tissue mass SDS increased
      continuously. Bone mineral content SDS started to increase after 6 months GHRx.
      Fat mass SDS decreased during the first 6 months of GHRx and remained stable
      thereafter. Biochemical parameters of bone formation and bone resorption did not
      differ from normal at baseline and increased during the first 6 months of GHRx.
      Serum 1,25 dihydroxyvitamin D increased continuously during GHRx, whereas PTH and
      serum calcium remained stable. Lipid profile was normal at baseline: Atherogenic
      index had decreased and apolipoprotein A1(Apo-A1) had increased after 3 yr of
      treatment. In conclusion, children with GHD have decreased bone mass. BMD,
      together with height and lean tissue mass, increased during GHRx. GHRx had a
      beneficial effect on lipid metabolism.

PMID- 9253312
TI  - Pituitary-adrenal suppression and recovery in preterm very low birth weight
      infants after dexamethasone treatment for bronchopulmonary dysplasia.
AB  - High dose dexamethasone is frequently used for the treatment of neonatal
      respiratory conditions and to facilitate weaning from mechanical ventilation in
      preterm, very low birth weight infants. However, very little is known about the
      severity, site, and duration of steroid-induced hypothalamic-pituitary-adrenal
      axis suppression in this category of patients. Twenty-three preterm, very low
      birth weight infants who received a full 3-week dose-tapering course of
      dexamethasone were prospectively studied, with a human CRH stimulation test
      performed at three different times: before the start of steroid treatment (week
      0), immediately after the course (week 3), and 4 weeks after stopping
      dexamethasone (week 7). Plasma ACTH and serum cortisol concentrations were
      measured at 0 (baseline), 15, 30, and 60 min. Immediately after the steroid
      course (week 3), both basal and poststimulation plasma ACTH and serum cortisol
      concentrations were markedly suppressed. The hormone concentrations at 0, 15, 30,
      and 60 min in week 3 were significantly lower than their corresponding levels in
      week 0 (P < 0.0001 for both ACTH and cortisol) and week 7 (P < 0.0001 and P <
      0.005 for ACTH and cortisol, respectively). In contrast, when the hormone levels
      in week 7 were compared to their corresponding concentrations in week 0, only the
      60 min serum cortisol concentration in week 7 was significantly lower (P = 0.02).
      The currently used dosage of dexamethasone caused severe pituitary-adrenal
      suppression immediately after treatment, but substantial recovery of the
      endocrine axis was observed 4 weeks after discontinuation of therapy. Although
      the recovery appeared to be earlier with the pituitary center, both pituitary and
      adrenal glands were capable of mounting a biochemically adequate response to
      exogenous human CRH stimulation at this stage. Steroid replacement therapy may be
      desirable at a time of stress in the immediate posttreatment period, but it would
      seem unnecessary 1 month after stopping dexamethasone treatment.

PMID- 9253313
TI  - Estrogen or testosterone increases self-reported aggressive behaviors in
      hypogonadal adolescents.
AB  - A randomized, double-blinded, placebo-controlled cross-over clinical trial was
      used to determine the role of sex steroids on the development of aggressive
      behaviors in 35 boys and 14 girls. Depo-testosterone (to boys) or conjugated
      estrogens (to girls) was administered in 3-month blocks alternating with placebo
      at three dose levels approximating early, middle and late pubertal amounts. The
      Olweus Multifaceted Aggression Inventory was administered after each placebo and
      treatment period to ascertain the effect of sex steroids on self-reported
      aggressive behaviors. We employed a strict intent-to-treat analytical model. The
      data demonstrated significant hormone effects on physical aggressive behaviors
      and aggressive impulses, but not in verbal aggressive behaviors nor aggressive
      inhibitions in both boys and girls. These results are the first to causally
      relate the administration of physiological doses of sex steroids to changes in
      aggressive behaviors in adolescents.

PMID- 9253314
TI  - Adrenocorticotropin- and cortisol-releasing effect of hexarelin, a synthetic
      growth hormone-releasing peptide, in normal subjects and patients with Cushing's
      syndrome.
AB  - GH-releasing peptides (GHRPs) are synthetic, nonnatural molecules that strongly
      stimulate GH secretion, but also slightly increase PRL, ACTH, and cortisol levels
      in man. To investigate the mechanism underlying the ACTH- and cortisol-releasing
      activity of GHRPs in man, we compared the ACTH- and cortisol-releasing activity
      of Hexarelin (HEX; 2.0 micrograms/kg, iv), a hexapeptide belonging to the GHRP
      family, with that of human CRH (hCRH; 2.0 micrograms/kg, iv) in normal subjects
      (6 men and 6 women, 24-68 yr old) and patients with Cushing's syndrome (2 men and
      15 women, 16-68 yr old). The GH response to HEX administration was also studied.
      In normal subjects, HEX administration significantly increased ACTH (peak us.
      baseline, mean +/- SD, 32.4 +/- 17.7 vs. 16.3 +/- 7.2 pg/mL; P < 0.005) and
      cortisol levels (135.9 +/- 51.0 vs. 110.0 +/- 31.6 micrograms/L; P < 0.01). The
      ACTH and cortisol responses to hCRH [35.7 +/- 13.2 vs. 17.1 +/- 7.7 pg/mL (P <
      0.01) and 162.8 +/- 50.1 vs. 102.8 +/- 28.1 micrograms/L (P < 0.01),
      respectively] were similar to the responses to HEX. The stimulatory effect of
      HEX, but not that of hCRH, on both ACTH and cortisol secretion in Cushing's
      disease was clearly higher (P < 0.01) than that observed in normal subjects. In
      fact, in Cushing's disease both HEX and hCRH elicited a clear increase in ACTH
      levels [381.1 +/- 350.0 vs. 52.4 +/- 25.0 (P < 0.005) and 100.0 +/- 86.2 vs. 53.3
      +/- 29.7 pg/mL (P < 0.01), respectively but the ACTH increase induced by HEX was
      about 7-fold greater (P < 0.02) than that induced by hCRH. Similarly, both HEX
      and hCRH elicited a significant increase in cortisol levels [366.9 +/- 189.5 vs.
      189.7 +/- 86.3 micrograms/L (P < 0.005) and 209.9 +/- 125.4 vs. 167.2 +/- 96.3
      micrograms/L (P < 0.02), respectively], but the cortisol increase induced by HEX
      was about 4-fold greater (P < 0.05) than that induced by hCRH. In patients with
      Cushing's syndrome due to adrenal adenoma or ectopic ACTH, no change in ACTH and
      cortisol levels was observed after either HEX or hCRH administration. The peak GH
      response to HEX in normal subjects was clearly higher (P < 0.03) than that in
      hypercortisolemic patients (45.8 +/- 20.5 vs. 22.4 +/- 21.1 micrograms/L). In
      conclusion, the ACTH- and cortisol-releasing activity of HEX is similar to that
      of hCRH in normal subjects, whereas it is dramatically enhanced in patients with
      Cushing's disease. This evidence indicates the importance of the ACTH-releasing
      activity of GHRPs and suggests that it could be at least partially independent of
      CRH-mediated mechanisms. As the stimulatory effect of HEX on ACTH and cortisol
      secretion is lost in patients with Cushing's syndrome due to adrenal adenoma or
      ectopic ACTH, these findings suggest the usefulness of GHRPs to investigate the
      activity of the hypothalamo-pituitary-adrenal axis in pathophysiological
      conditions and possibly to differentiate pituitary from ectopic ACTH-dependent
      Cushing's syndrome.

PMID- 9253315
TI  - The efficiency of dietary protein utilization is increased during puberty.
AB  - We investigated whether the efficiency of dietary protein utilization for growth
      increases during the pubertal growth spurt in both nondiabetic and diabetic
      subjects. We measured leucine oxidation and retention (intake minus oxidation) in
      orally fed nondiabetic (n = 9) and diabetic (n = 9) human subjects, aged 7-17 yr.
      Eight subjects were Tanner stage I, and 10 were Tanner stages III-V; groups were
      not matched for gender. After 3 days of consuming a diet containing approximately
      1 g/kg. day protein, subjects drank a commercial liquid nutrition formula,
      containing L-[1(-13)C]leucine, every 30 min for a total of 6 h to provide 1 g
      protein/kg. day. Isotopic enrichment of CO2 was used to calculate the fractional
      leucine oxidation rate and, together with alpha-ketoisocaproate isotopic
      enrichment, to calculate total leucine oxidation. Leucine oxidation rates
      decreased with puberty in both nondiabetic subjects (36.0 +/- 10.4 vs. 23.9 +/-
      4.2 mumol/kg fat-free mass (FFM).h, prepubertal and pubertal, respectively; P <
      0.05) and diabetic (33.6 +/- 4.9% vs. 27.3 +/- 3.4 mumol/kg FFM.h, prepubertal
      and pubertal, respectively; P < 0.1) subjects. Leucine retention increased with
      puberty in both nondiabetic (0.27 +/- 3.2 vs. 15.7 +/- 5.3 mumol/kg FFM.h,
      prepubertal and pubertal, respectively; P < 0.001) and diabetic (1.9 +/- 4.9 vs.
      13.2 +/- 4.4 mumol/kg FFM.h, prepubertal and pubertal subjects, respectively; P <
      0.05) subjects. The data suggest that the pubertal growth spurt is associated
      with a marked increase in the efficiency of dietary protein utilization for
      growth.

PMID- 9253316
TI  - Cardiovascular abnormalities in patients with X-linked hypophosphatemia.
AB  - Treatment for X-linked hypophosphatemia (XLH; vitamin D metabolites and phosphate
      salts) may result in hypercalcemia, hypercalciuria, nephrocalcinosis, and
      hyperparathyroidism. Cardiovascular abnormalities occur in association with these
      complications, but have not been reported in XLH. We hypothesized that such
      abnormalities may occur in XLH and evaluated cardiovascular status in 13 patients
      with this disease. All patients were asymptomatic and had normal cardiovascular
      physical examinations and Holter studies. Serum calcium and creatinine clearance
      were normal in all. However, all patients had mild to moderate nephrocalcinosis.
      Left ventricular hypertrophy was diagnosed by electrocardiogram in three and by
      ultrasonography in seven children. Baseline blood pressure (BP) was normal (mean
      +/- SD, 116 +/- 15/74 +/- 6 mm Hg). During exercise stress testing, systolic BP
      increased in all patients, but the maximal systolic pressure was less than that
      in healthy age- and sex-matched controls (156 +/- 20 vs. 175 +/- 23; P = 0.002,
      by t test). An abnormal increase in diastolic BP occurred at all levels of work
      load in XLH patients; their peak exercise diastolic BP was 91 +/- 12 vs. 72 +/- 6
      mm Hg in controls (P < 0.0001, by t test). Whether these abnormal findings are
      primary defects in XLH or represent complications of treatment is unclear.
      Patients with XLH should be monitored closely for the development of hypertension
      and left ventricular hypertrophy. Investigation of the mechanisms involved and
      establishment of therapeutic guidelines are indicated.

PMID- 9253317
TI  - Thyroiditis after pregnancy loss.
AB  - We present a case series evaluating the development and characteristics of
      thyroiditis following pregnancy loss. Five women were followed prospectively with
      measurement of thyroid function and antithyroid antibodies after pregnancy loss.
      Serum TSH concentrations were measured by immunoradiometric assay and antithyroid
      antibodies by RIA and hemagglutination techniques. All women had normal serum TSH
      concentrations before conception or at the time of pregnancy loss, and all but
      one had positive antithyroid antibodies. Pregnancy loss occurred between 5-20
      weeks gestation because of ectopic pregnancy or either spontaneous or elective
      abortion. Two women had subclinical hypothyroidism with peak serum TSH values of
      8.7 mU/L and 5.4 mU/L at 2 and 7 months after pregnancy loss, respectively. Three
      women had clinical hyperthyroidism with serum TSH values < or = 0.2 mU/L
      diagnosed between 3-11 months after pregnancy loss followed subsequently by a
      hypothyroid phase. Painless thyroiditis within 1 yr of pregnancy loss in these
      women suggests that the immunological changes of a short-term gestation may be
      sufficient to lead to thyroiditis.

PMID- 9253318
TI  - Increase in urinary cortisol excretion and memory declines: MacArthur studies of
      successful aging.
AB  - Cortisol production is increased during stress, and the actions of cortisol on
      receptors in the brain and other body organs are involved in allostasis, the
      process of adaptation to stress, as well as in allostatic load, the wear and tear
      associated with excessive exposure to cortisol. Using data from a community-based
      longitudinal study of older men and women, aged 70-79 yr, we tested the
      hypothesis that exposure to increasing levels of cortisol is associated with
      declines in memory performance. Associations between 12-h urinary free cortisol
      excretion and performance on tests of memory (delayed verbal recall and spatial
      recognition), abstraction, and spatial ability were examined. Among the women,
      greater cortisol excretion was associated with poorer baseline memory
      performance, independent of socio-demographic, health status, health behavior,
      and psychosocial characteristics. Moreover, women who exhibited increases in
      cortisol excretion over a 2.5-yr follow-up period were more likely to show
      declines in memory performance. By contrast, women who experienced declines in
      cortisol exhibited improvements in memory performance. No significant
      associations were found among the men. The results for the women suggest that
      decrements in memory performance associated with increases in cortisol may not
      represent irreversible effects, as declines in cortisol were associated with
      improvements in memory.

PMID- 9253319
TI  - An overnight insulin infusion algorithm provides morning normoglycemia and can be
      used to predict insulin requirements in noninsulin-dependent diabetes mellitus.
AB  - Initial insulin requirements in noninsulin-dependent diabetes mellitus (NIDDM)
      are difficult to estimate because of individual variability in insulin
      sensitivity and secretion. We evaluated a simple, nurse-managed algorithm for
      overnight delivery of insulin, for its ability to provide morning near
      normoglycemia and as a means to predict initial insulin requirements in NIDDM.
      Twenty-seven patients with poorly controlled NIDDM were studied on 30 occasions.
      A 12-h iv insulin infusion was begun at 2000 h, and bedside blood glucose
      concentrations were measured at hourly intervals. The rate of insulin infusion
      was adjusted according to blood glucose levels. We estimated the preprandial
      insulin dose requirement for the following day in 16 patients based on overnight
      insulin requirements to maintain normoglycemia. Preprandial insulin doses were
      adjusted for prevailing blood glucose concentrations. At 2000 h, the mean (+/
      SEM) blood glucose concentration was 265.7 +/- 10.8; at 0300 h, it was 122.8 +/-
      3.4; and at 0700 h, it was 123.8 +/- 5.1 mg/dL. On the next day, mean blood
      glucose levels (before and 2 h after a meal) were: breakfast, 102.5 +/- 5.9 and
      177.3 +/- 19.2; lunch, 138.9 +/- 15.5 and 136.3 +/- 11.4; dinner, 105.7 +/- 7.2
      and 178.1 +/- 15.7 mg/dL. There was no significant difference between mean
      calculated and administered total insulin dosage the next day (84.2 +/- 7.0 vs.
      78.2 +/- 8.2 U). Thus, a weight-based algorithm for iv insulin infusion induced
      near-normoglycemia in NIDDM and successfully predicted the insulin dose
      requirement. We conclude that initiating insulin therapy in NIDDM patients can be
      achieved rapidly and efficiently based on a nurse-managed overnight insulin
      infusion.

PMID- 9253320
TI  - Experimental transplantation of human fetal and adult pancreatic islets.
AB  - We examined morphology and function following transplantation of human fetal
      islet-like clusters (ICCs) in nude mice and compared the functional efficiency of
      human adult islets and fetal ICCs after transplantation. To assess the optimal
      site we first transplanted ICCs under the kidney capsule, pancreas, lung, and
      liver in nude mice. Grafts to the kidney and pancreas matured functionally and
      morphologically, as evidenced by a 4-fold increase in C peptide after glucose
      stimulation and the presence of insulin in the grafts of all animals. Grafts to
      the lung, liver, and spleen did poorly; C peptide was only measurable in two of
      eight, two of five, or three of five of mice grafted to the lung, liver, or
      spleen, respectively. Using chemically diabetic nude rats as recipients, we were
      able to restore normoglycemia using 15,000 ICCs/kg. Lastly, when transplanted
      under the kidney capsule of normal nude mice, ICCs had significantly higher
      insulin contents and C peptide release than equivalent grafts of adult islets. In
      summary, ICCs are an efficient source of insulin-producing cells of potential use
      in clinical transplantation. In nude mice, both the kidney and the pancreas
      provide suitable environments for the growth and maturation of undifferentiated
      human beta-cells.

PMID- 9253321
TI  - Biochemical bone markers and bone mineral density during postmenopausal hormone
      replacement therapy with and without vitamin D3: a prospective, controlled,
      randomized study.
AB  - The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D on
      the serum concentrations of three bone biochemical markers and their associations
      with bone mineral density (BMD) were studied in a population-based 1-yr follow-up
      study. A total of 72 healthy postmenopausal women were randomized into 4
      treatment groups: HRT group (sequential combination of 2 mg estradiol valerate
      and 1 mg cyproterone acetate), D group (vitamin D3, 300 IU/day), HRT+D group
      (both of the above), and placebo group (calcium lactate, 500 mg/day). Serum
      concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP)
      were measured as biochemical markers of bone formation, and serum type I collagen
      carboxy-terminal telopeptide was measured as a marker of bone resorption at
      baseline and after 6 and 12 months of treatment. To investigate the associations
      of these markers with BMD, lumbar (L2-L4) and femoral neck BMDs were determined
      by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both
      hormone groups, the serum concentrations of the three bone metabolic markers had
      decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT
      group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrations
      decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the
      HRT+D group. Serum type I collagen carboxy-terminal telopeptide concentrations
      had decreased by 21.6% (P = 0.012) in HRT group and by 14.1% (P = 0.011) in the
      HRT+D group. In the D group, the serum concentrations of BAP had decreased by
      11.7% (P = 0.040) after 12 months, but the other two markers showed no change.
      The only change seen in the placebo group was a 19.2% increase in OC
      concentrations (P = 0.041) after 6 months, but at 12 months, the mean OC level
      was similar to that at baseline. After 2.5 yr, both lumbar and femoral BMD had
      decreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019), respectively]
      and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010), respectively],
      whereas no significant changes occurred in the hormone groups. There were
      significant inverse correlations between the changes in lumbar and femoral BMDs
      and changes in all three biochemical markers (r = -0.240 through -0.336; P =
      0.005-0.064). Our results suggest that HRT counteracts the biochemical changes
      caused by increased bone turnover associated with menopause. Importantly, the
      changes in bone markers correlate with long term changes in BMDs of lumbar spine
      and femoral neck. Low dose vitamin D treatment, however, seems to have only
      marginal effects on bone metabolism in early postmenopausal healthy women.

PMID- 9253322
TI  - Lipoprotein subfraction changes in normal pregnancy: threshold effect of plasma
      triglyceride on appearance of small, dense low density lipoprotein.
AB  - A detailed longitudinal examination of plasma lipoprotein subfraction
      concentrations and compositions in pregnancy was performed with the objective of
      discovering the pattern of change in lipoprotein subfractions. Plasma
      triglyceride, cholesterol, very low density lipoprotein (VLDL1), very low density
      lipoprotein (VLDL2), intermediate density lipoprotein (IDL), low density
      lipoprotein (LDL) and its subfractions (LDL-I, LDL-II, LDL-III), and high density
      lipoprotein-cholesterol (HDL cholesterol) were quantified in 10 normal pregnant
      women from 10 weeks of gestation and at 5 weekly intervals thereafter, until 35
      weeks of gestation, together with circulating hepatic lipase (at 10 and 35 weeks)
      and serum estradiol concentration. Median concentrations of VLDL1 (19-109 mg/dL),
      VLDL2 (17-103 mg/dL) and IDL (26-124 mg/dL) increased in parallel (maximum
      increase around 5-fold) as plasma triglyceride increased with advancing
      gestation. This contrasts with observations in the normal non-pregnant female,
      where higher concentrations of plasma triglyceride are associated with
      preferentially higher VLDL1 concentrations. The rise in IDL was also remarkable
      as this does not normally accompany changes in plasma triglyceride. LDL mass
      increased by 70% (200-353 mg/dL) between 10 and 35 weeks, and in 6 of the 10
      women studied, the LDL subfraction pattern was modified towards a smaller denser
      pattern in a manner suggestive of a "threshold" transition, with the proportion
      of LDL-III increasing at the expense of LDL-II, whereas in the other 4 women, LDL
      subfraction profile remained unchanged throughout pregnancy. Interestingly, this
      "threshold" transition, if it occurred, did so at varying gestational ages and
      triglyceride concentrations for different women. The likelihood of LDL
      subfraction change and the final concentration of small, dense. LDL-III were
      related to the 10-week triglyceride concentration (R2 = 36.7%, P = 0.063) and to
      the rate of change in triglyceride for a given increment in estrogen (R2 = 48.6%,
      P = 0.025). In addition, VLDL1 mass exceeded 100 mg/dL during pregnancy only in
      those individuals in whom LDL profile perturbation was evident (chi 2, P <
      0.001). LDL profile change was evident at the lowest triglyceride concentrations
      in the 2 individuals with the highest increments in triglyceride corrected for
      estrogen. On the basis of these longitudinal observations, we conclude the
      following: 1) as plasma triglyceride increases in pregnancy, there are parallel
      rises in median concentrations of VLDL1, VLDL2 and IDL, around 5-fold; 2) as a
      result of this progressive increase in plasma triglyceride, in particular in
      VLDL1, the LDL profile is altered in some individuals towards smaller, dense
      particles; 3) in general, the higher the initial (booking) fasting plasma
      triglyceride concentration or the larger the rate of change in triglyceride for a
      given increment in estradiol, the greater the probability of change in LDL
      profile towards smaller denser species; 4) significantly, LDL subclass
      perturbation towards smaller denser species occurs not in a gradual and
      progressive manner but exhibits "threshold" behavior; and finally, 5) this
      threshold is achieved at differing gestational ages and triglyceride
      concentrations for different women.

PMID- 9253323
TI  - Growth hormone response to the hypothalamic somatostatinergic activity in
      acromegalic patients.
AB  - Oral glucose administration suppresses the TRH-induced TSH response by enhancing
      the hypothalamic somatostatinergic activity (HSA). We assessed the HSA in 13
      acromegalic patients by measuring glucose-induced suppression of TRH-stimulated
      TSH secretion. The HSA showed wide variation with up to 64% suppression. The mean
      HSA of the patients (25 +/- 6%) did not differ from that in normal young men (19
      +/- 4%) in our previous study. Six patients had normal or low HSA, and the other
      7 patients had high HSA. The mean TRH-stimulated TSH levels of the patients with
      normal or low HSA was significantly lower than that of the patients with high HSA
      (5.13 +/- 0.10 vs. 11.30 +/- 2.80 mU/L). The HSA did not relate to sex, age,
      tumor size, basal GH levels, the paradoxical responses to TRH and GnRH,
      octreotide response, or the gsp oncogene. In the combined glucose-TRH test,
      glucose pretreatment completely suppressed the paradoxical increase in GH level
      at 30 min in 4 patients. However, it could suppress the paradoxical GH response
      by only 6-51% in the other 5 patients who also showed the paradoxical response in
      TRH test. The tumor diameter of patients with good response to the HSA was
      significantly larger than that of the patients with poor response (31 +/- 5 vs.
      14 +/- 2 mm) as was the tumor grade (3.3 +/- 0.3 vs. 1.7 +/- 0.2). This study
      supports the idea that a reduction of HSA is not a primary cause of acromegaly,
      and the HSA seems to increase to suppress the autonomous secretion of GH from the
      pituitary adenomas. HSA as well as the response of tumors to HSA do not determine
      tumor growth.

PMID- 9253324
TI  - Free insulin-like growth factor I serum levels in 1430 healthy children and
      adults, and its diagnostic value in patients suspected of growth hormone
      deficiency.
AB  - Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding
      protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which
      makes them good diagnostic markers for screening of GH deficiency (GHD) in short
      children, although some controversy still exists. Only a minor fraction of the
      total IGF-I circulates in its free form, which is believed to be the biologically
      active form. However, our knowledge of the clinical or physiological value of
      determination of free IGF-I in serum is limited at present. In adults, the
      diagnostic value of total IGF-I and IGFBP-3 determinations in patients suspected
      of GHD has only been reported in a few studies, whereas no previous reports on
      the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum
      levels of free IGF-I were determined in 1430 healthy children, adolescents, and
      adults by a newly developed, commercially available immunoradiometric assay
      (Diagnostic Systems Laboratories) to establish valid normative data for this
      analysis. We studied the diagnostic value of free IGF-I in relation to total IGF
      I and IGFBP-3 determinations in adults who were suspected of GHD. A GH
      provocative test, using oral clonidine, was performed in 108 adult patients who
      had previously been treated with GH in childhood. In healthy subjects, free IGF-I
      levels increased during childhood, with the highest mean values during puberty.
      After puberty, a subsequent decline in serum levels of free IGF-I was apparent.
      We found, unmeasurable free IGF-I values in 34 of the prepubertal children
      (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that
      amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels
      were below--2 SD in 56 of 79 GHD patients (sensitivity, 71%) and above--2 SD in
      24 of 29 patients with a normal GH response (specificity, 83%). Multiple linear
      regression analysis demonstrated that free IGF-I was significantly dependent on
      peak GH levels, duration of the disease, and number of other pituitary axes
      affected. We conclude that free IGF-I serum levels increase during childhood with
      a peak in puberty, whereafter free IGF-I levels return to prepubertal levels.
      Three percent of healthy prepubertal children had unmeasurable free IGF-I levels
      using this assay. We found that determination of the free IGF-I serum
      concentration may predict the outcome of a GH provocative test in adults
      suspected of GHD, but that a single determination of free IGF-I offered no
      significant advantage compared to determination of total IGF-I or IGFBP-3 serum
      levels.

PMID- 9253325
TI  - Hormonal responses to psychological stress in men preparing for skydiving.
AB  - The purpose of the study was to examine the relationship between the hormonal and
      psychological responses of young men about to engage in a potentially life
      threatening event. Subjects were recruited to take their first skydiving jump.
      The scores on questionnaires designed to assess anxiety were not significantly
      increased at 0800 h on the morning before the jump by comparison with scores
      obtained from the same subjects 3-5 days previously. However, a psychological
      instrument for rating of events indicated significantly increased intensity, and
      sympathetic nervous system activity, as measured by the salivary amylase
      response, was increased over self-control values. Salivary cortisol and
      testosterone levels were significantly lower on the morning of the jump than self
      control values and values in control subjects determined at the same time of day.
      However, plasma LH was not suppressed. The anxiety and stress measures as well as
      the rating of events rose to high levels just before the jump. With the exception
      of testosterone, which remained low, serum cortisol, PRL, and GH all increased
      greatly subsequent to the rise in psychological measures, reached peak values
      before or shortly after landing, and declined significantly within the next hour.
      Anxiety and subjective stress scores declined to those of the self-control values
      within 15 min after landing, but the rating of events scale remained
      significantly elevated. In summary, reported anxiety associated with a purely
      psychological stressor was suppressed until within a few hours preceding the
      event, but was preceded by an increase in sympathetic nervous system activity and
      suppression of plasma cortisol and salivary testosterone levels. The event itself
      was associated with a reversal of the cortisol decline; other stress-associated
      hormones increased, but salivary testosterone remained low.

PMID- 9253326
TI  - Testosterone substitution normalizes elevated serum leptin levels in hypogonadal
      men.
AB  - The ob gene product leptin (OB) is a feedback signal from the adipocyte to the
      hypothalamus and is involved in regulation of food intake and energy expenditure
      in rodents. A major determinant of serum OB levels is fat mass. Several studies
      suggest that men have lower OB levels than women even after adjustment for
      percent body fat. We, therefore, investigated the influence of testosterone (T)
      substitution in hypogonadal men on serum OB levels. Hypogonadal men with T levels
      of 3.6 nmol/L or less and off substitution therapy for at least 3 months were
      assigned to two treatment groups: testosterone enanthate (TE; 250 mg, i.m., every
      21 days; n = 10) or a single s.c. implantation of 1200 mg crystalline T (TPEL; n
      = 12). Blood samples for determination of T, 5 alpha-dihydrotestosterone (DHT),
      sex hormone-binding globulin, and 17 beta-estradiol were obtained before therapy
      and then every 21 days until day 189 and at follow-up visits on days 246 and 300.
      Serum OB levels were assessed on days 0, 42, 84, 126, 168, and 300. OB levels
      were referred to a normal range for men based on the analysis of OB levels in 393
      adult men. Substitution with T led to a large rise in T and DHT in both groups
      compared to baseline values (average T, days 21-189: TE, 14.33 +/- 2.63 nmol/L;
      TPEL, 24.98 +/- 1.64; average DHT, days 21-189: TE, 4.20 +/- 0.57 nmol/L; TPEL,
      5.11 +/- 0.56; P < or = 0.05). Concomitantly, 17 beta-estradiol increased in both
      groups, and sex hormone-binding globulin levels were significantly decreased. At
      baseline, serum OB levels in hypogonadal men were 3-fold elevated compared to
      those in normal men (12.39 +/- 2.93 micrograms/L vs. 4.28 +/- 0.52; P < 0.01) and
      not different between groups (TE, 13.7 +/- 5.6; TPEL, 11.3 +/- 2.9 micrograms/L).
      This elevation was retained after adjustment for body mass index in the normal
      control group [TE, 1.45 +/- 0.51 SD score (P < 0.0001); TPEL, 0.98 +/- 0.35 SD
      score (P < 0.0008)]. During T substitution serum OB was completely normalized
      (trough levels: TE, 4.6 +/- 1.0 micrograms/L; TPEL 4.3 +/- 0.9 micrograms/L). In
      multiple regression analysis, the androgen (T plus DHT)/estrogen ratio was the
      only significant determinant of OB levels (r = -0.32; P < 0.01). At baseline, OB
      levels did not correlate with body mass index, but during substitution, the
      correlation was considerably improved. We conclude that hypogonadal men exhibit
      elevated OB levels that are normalized by substitution with T. The only
      determinant of OB levels was the androgen/estrogen ratio, indicating a major
      influence of sex steroids on OB production. The interaction of T and OB might be
      part of a hypothalamic-pituitary-gonadal-adipose tissue axis that is involved in
      body weight maintenance and reproductive function.

PMID- 9253327
TI  - Glucose homeostasis in children with falciparum malaria: precursor supply limits
      gluconeogenesis and glucose production.
AB  - To evaluate glucose kinetics in children with falciparum malaria, basal glucose
      production and gluconeogenesis and an estimate of the flux of the gluconeogenic
      precursors were measured in Kenyan children with uncomplicated falciparum malaria
      before (n = 11) and during infusion of alanine (1.5 mg/kg.min; n = 6). Glucose
      production was measured by [6,6-2H2]glucose, gluconeogenesis by mass isotopomer
      distribution analysis of glucose labeled by [2-13C]glycerol. Basal plasma glucose
      concentration ranged from 2.1-5.5 mmol/L, and basal glucose production ranged
      from 3.3-7.3 mg/kg.min. Glucose production was largely derived from
      gluconeogenesis (73 +/- 4%; range, 52-93%). During alanine infusion, plasma
      glucose increased by 0.4 mmol/L (P = 0.03), glucose production increased by 0.8
      mg/kg.min (P = 0.02), and gluconeogenesis increased by 0.8 mg/kg.min (P = 0.04).
      We conclude that glucose production in children with uncomplicated falciparum
      malaria is largely dependent on gluconeogenesis. However, gluconeogenesis is
      potentially limited by insufficient precursor supply. These data indicate that in
      children with falciparum malaria, gluconeogenesis fails to compensate in the
      presence of decreased glycogen flux to glucose, increasing the risk of
      hypoglycemia.

PMID- 9253329
TI  - Effects of insulin-like growth factor I combined with growth hormone on
      glucocorticoid-induced whole-body protein catabolism in man.
AB  - Treatment with insulin-like growth factor I (IGF-I) alone failed to affect
      glucocorticoid-induced protein catabolism in a previous study from our
      laboratory. To assess the effects of the combination of IGF-I and GH in a similar
      protocol, 24 normal subjects received (in a double-blind, randomized, placebo
      controlled manner) s.c. injections of either GH alone (0.3 IU/kg.day), the
      combination of IGF-I (80 micrograms/kg.day) and GH (0.3 IU/kg.day), or placebo
      for a period of 6 days during which they were treated with methylprednisolone
      (0.5 mg/kg.day). Whole-body protein kinetics measured, using the [1-13C]-leucine
      infusion technique, demonstrated that leucine flux (a parameter of protein
      breakdown) increased during administration of glucocorticoids alone (placebo
      group) and during GH-treatment, whereas the glucocorticoid-induced increase was
      abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation (a parameter
      of irreversible protein catabolism) increased in the placebo group (+60 +/-
      14.5%, P < 0.005, day 7 vs. day 1), remained unchanged in the GH group (+2.5 +/-
      10%), and decreased in the combination group (-17.7 +/- 3.3%, P < 0.002, day 7
      vs. day 1). Glucose MCR decreased in the group receiving placebo (P < 0.05) and
      remained unchanged during combined treatment with IGF-I plus GH. It is concluded
      that glucocorticoid-induced protein, catabolism (leucine oxidation) is abolished
      during coadministration of GH (anticatabolic effect), whereas treatment with IGF
      I and GH results in a net anabolic effect without adverse effects on peripheral
      glucose clearance.

PMID- 9253328
TI  - Ribonucleic acid expression of the CLA-1 gene, a human homolog to mouse high
      density lipoprotein receptor SR-BI, in human adrenal tumors and cultured adrenal
      cells.
AB  - Human CLA-1 is homologous to the mouse SR-BI gene, which was recently identified
      as a high density lipoprotein receptor involved in selective cholesterol uptake
      in rodent adrenal cells. We screened 42 normal and pathological adrenal samples
      by Northern blotting and found abundant expression of CLA-1 messenger ribonucleic
      acid (mRNA) in normal adult and fetal adrenals, adrenocortical adenomas, and
      hyperplasias. Adrenocortical carcinomas and the adrenals adjacent to Cushing's
      adenomas contained less CLA-1 mRNA than normal adrenals. CLA-1 mRNA was also
      highly expressed in a Leydig cell tumor, but much less in liver, kidney, and
      pheochromocytomas. The accumulation of CLA-1 mRNA in primary cultures of normal
      adrenocortical cells was up-regulated by ACTH in a dose- and time-dependent
      manner. Both dibutyryl cAMP and staurosporine increased the basal expression of
      CLA-1 mRNA. Although there was no additive effect of ACTH and dibutyryl cAMP,
      staurosporine slightly enhanced the stimulatory effect of ACTH on the expression
      of CLA-1 mRNA. The abundant expression of CLA-1 mRNA and its regulation by the
      physiological hormone ACTH in human adrenal cells suggest that CLA-1 has a role
      in adrenal steroidogenesis, probably as a lipoprotein receptor mediating the
      selective cholesterol uptake in these cells.

PMID- 9253330
TI  - Interplay between sex steroids and melatonin in regulation of human benign
      prostate epithelial cell growth.
AB  - Human benign prostatic epithelial cells contain functional melatonin receptors
      that can suppress cell growth and viability. The development of benign prostatic
      hyperplasia in men is assumed to result from androgen-estrogen imbalance. The
      impact of sex steroids on melatonin receptors in human benign prostate epithelial
      cells was investigated. The suppression by melatonin of [3H]thymidine
      incorporation and cGMP, and the enhancement of cAMP levels in the cells were used
      as markers of melatonin responses. Dihydrotestosterone (DHT) and 17 beta
      estradiol (E2) separately increased [3H]thymidine incorporation into the cells,
      but suppressed it when combined. In cells grown with DHT, melatonin responses
      were extenuated. E2 greatly reduced the apparent affinity of [125I]melatonin
      binding in these cells without affecting binding site density. In parallel, the
      ability of melatonin to suppress [3H]thymidine incorporation into the cells was
      ablated within 1 h after the addition of E2. The melatonin-mediated increase in
      cAMP and decrease in cGMP concentrations were also ablated by E2. Preincubation
      of the cells with bis-indolylmaleimide (GF 102903X), a specific inhibitor of
      protein kinase C, prevented the E2-mediated inactivation of melatonin binding and
      the inhibitory action on [3H]thymidine incorporation. Prolonged (18-h) incubation
      of the cells with phorbol 12-myristate 13-acetate to down regulate protein kinase
      activity, partially restored [125I]melatonin binding and responsiveness in the E2
      treated cells. These data indicate that 1) DHT and E2 enhance prostate epithelial
      cells growth, but reduce cell growth when combined; 2) DHT extenuates the
      inhibitory effects of melatonin on epithelial cell growth; and 3) E2 acts to
      inactivate melatonin receptors and consequently responses in human epithelial
      benign prostatic hyperplasia cells. This process is probably mediated by protein
      kinase C. Together, these results show an interplay between melatonin and sex
      steroids in the regulation of benign prostatic epithelial cell growth.

PMID- 9253331
TI  - Glucocorticoid regulation of leptin synthesis and secretion in humans: elevated
      plasma leptin levels in Cushing's syndrome.
AB  - Leptin, the obese (ob) gene product, is an adipocyte-derived satiety factor that
      is involved in the regulation of food ingestion and body weight. To investigate
      glucocorticoid regulation of leptin synthesis and secretion in humans, we
      measured plasma leptin levels in patients with Cushing's syndrome with adrenal or
      pituitary adenoma and in patients with iatrogenic Cushing's syndrome. Plasma
      leptin levels in patients with Cushing's syndrome were significantly elevated
      compared to those in nonobese healthy subjects and obese subjects without any
      metabolic or endocrine diseases at a given percentage of body fat by analysis of
      covariance. In patients with adrenal or pituitary adenoma, after the tumor
      resection, plasma leptin levels were reduced, with a concurrent decrease in
      plasma cortisol levels. With no significant changes in body weight, plasma leptin
      levels were also elevated significantly in lean healthy volunteers 24 h after the
      administration of 1 mg dexamethasone. Dexamethasone potently induced ob gene
      expression and leptin secretion in the organ culture of human adipose tissue. The
      data demonstrate that glucocorticoids act, at least in part, directly on the
      adipose tissue and increase leptin synthesis and secretion in humans.

PMID- 9253332
TI  - Hemodynamic effects of parathyroid hormone-related peptide-(1-34) in humans.
AB  - It has been suggested that PTH-related peptide-(1-34) (PTHrP) is a regulator or
      modulator of regional or systemic cardiovascular function with varying
      vasodilating actions in different species. We have studied the cardiovascular
      pharmacodynamic profile of PTHrP in healthy humans. In a double blind, placebo
      controlled, cross-over study design, eight healthy subjects were assigned to
      stepwise increased i.v. doses of PTHrP. In addition, a dose-response curve to
      PTHrP was constructed in a dorsal hand vein in eight subjects. PTHrP dose
      dependently increased pulse rate and renal plasma flow by more than 50% (P <
      0.0001 for both parameters, by ANOVA), but only a small venodilating response was
      seen in hand vein experiments, and no effect was noted on mean arterial blood
      pressure or cardiac inotropic performance. Although it is unlikely that PTHrP
      regulates systemic hemodynamics, its chronotropic effect and its potent action on
      renal plasma flow may represent the primary cardiovascular physiological targets
      of action.

PMID- 9253333
TI  - Protein metabolism in human obesity: relationship with glucose and lipid
      metabolism and with visceral adipose tissue.
AB  - It is controversial whether metabolic disorders of human obesity include protein
      metabolism. Even less information is available concerning the effect of fat
      distribution on protein metabolism. Therefore, a comprehensive evaluation of
      glucose, lipid, and protein metabolism was performed in 11 obese nondiabetic and
      9 normal women whose body composition and regional fat distribution were
      determined. [1-14C]Leucine and [3-3H]glucose were infused in the postabsorptive
      state and during an euglycemic hyperinsulinemic (35-40 microU/mL) clamp combined
      with indirect calorimetry for assessment of leucine flux, oxidation, and
      nonoxidative disposal, glucose turnover and oxidation, and lipid oxidation. Fat
      free mass (FFM) was estimated by a bolus of 3H2O. Subcutaneous abdominal and
      visceral adipose tissues were determined by nuclear magnetic resonance imaging.
      During the clamp, obese women had lower glucose turnover (4.51 +/- 0.41 vs. 6.63
      +/- 0.40 mg/min.kg FFM; P < 0.05), with a defect in both oxidation (3.27 +/- 0.22
      vs. 3.89 +/- 0.21) and nonoxidative disposal (1.24 +/- 0.27 vs. 2.74 +/- 0.41; P
      < 0.005), whereas lipid oxidation was higher during the clamp (0.49 +/- 0.15 vs.
      0.17 +/- 0.09 mg/min.kg FFM). There was no difference in leucine flux (basal,
      2.23 +/- 0.17 vs. 2.30 +/- 0.29; clamp, 2.06 +/- 0.19 vs. 2.10 +/- 0.24
      mumol/min.kg FFM), oxidation (basal, 0.37 +/- 0.04 vs. 0.36 +/- 0.05; clamp, 0.34
      +/- 0.04 vs. 0.39 +/- 0.06) and nonoxidative leucine disposal (basal, 1.86 +/-
      0.17 vs. 1.94 +/- 0.26; clamp, 1.72 +/- 0.20 vs. 1.71 +/- 0.19) in the two
      groups. In obese women, basal leucine oxidation was directly related with glucose
      oxidation and inversely to lipid oxidation (both P < 0.05), whereas visceral
      adipose tissue was inversely related to leucine flux both in the basal state and
      during the clamp (P < 0.05). In conclusion, in human obesity, 1) rates of protein
      metabolism in the basal state and in the range of insulin concentrations
      encountered after a meal are normal; 2) protein oxidation is positively related
      to glucose oxidation and negatively related to lipid oxidation; and 3) visceral
      adipose tissue is inversely related to all parameters of protein metabolism.

PMID- 9253334
TI  - Structural and functional abnormalities at 11p15 are associated with the
      malignant phenotype in sporadic adrenocortical tumors: study on a series of 82
      tumors.
AB  - Abnormalities of the 11p15 region with overexpression of the normally imprinted
      insulin-like growth factor II (IGF-II) gene have been implicated in the
      pathogenesis of adrenocortical tumors. We evaluated the frequency and
      distribution of 11p15 loss of heterozygosity (LOH) and IGF-II gene overexpression
      in a series of 82 sporadic adrenocortical tumors, screened for pathological
      functional imprinting of the 11p15 region in tumors not exhibiting LOH and
      evaluated the expression of H19 gene in these tumors. Abnormalities of the 11p15
      region as LOH (loss of the maternal allele and duplication of the paternal
      allele) and/or IGF-II gene overexpression are frequent features of the malignant
      state and were found in 27 of 29 (93.1%) of the malignant tumors and in only 3 of
      35 (8.6%) of the benign tumors. Tumors without abnormality of the 11p15 region
      (mainly benign tumors) did not exhibit pathological functional imprinting. In
      tumors with mosaicism for 11p15 LOH, biallelic expression of the IGF-II gene was
      constant in the tumor cell contingent not undergoing LOH. Abrogation of H19
      expression correlated with the loss of the maternal allele (LOH or pathological
      imprinting), but did not always correlate with overexpression of the IGF-II gene.
      These data indicate the involvement of dysregulation of the 11p15 region in late
      steps of adrenocortical tumorigenesis and provide us with new molecular markers
      for a better diagnostic and prognostic evaluation of adrenocortical tumors.

PMID- 9253335
TI  - Different expression patterns of somatostatin receptor subtypes in cultured
      epithelial cells from human normal prostate and prostate cancer.
AB  - The transcripts of five SRIH receptor subtypes (SSTR1, SSTR2, SSTR3, SSTR4, and
      SSTR5) were investigated by RT-PCR in epithelial cells (EC) and stromal cells
      (SC) from primary cultures of five normal human prostates and six prostate
      cancers. Primary cultures of prostate EC were established in serum-free
      keratynocyte medium with 5% FCS, epidermal growth factor, and bovine pituitary
      extract; SC were cultured in MEM with 10% FCS. Total RNA was extracted from EC
      and SC using a modified guanidine thiocyanate method. RT-PCR was performed after
      deoxyribonuclease treatment, using SSTR1-, SSTR2-, SSTR3-, SSTR4-, and SSTR5
      specific-primers and adding glyceraldehyde-3-phosphate dehydrogenase-specific
      primers as internal control. A PCR product of the expected size of 334 bp,
      corresponding to SSTR1, was expressed only in EC from prostate cancer, whereas
      the expected 461-bp product of SSTR2 was found only in EC from normal prostate.
      SSTR3 messenger RNA was undetectable in normal and cancer EC, whereas SSTR4 and
      SSTR5 were present in both cell types. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5
      messenger RNAs were not expressed in SC from both normal and cancer prostates.
      The RT-PCR method clearly demonstrated SSTRs' expression in the human prostate EC
      in vitro with differences between normal and tumoral samples. Our results may
      explain the ineffectiveness of some SSTR2 selective SRIH analogues in the
      treatment of prostate cancer and suggest that the absence of SSTR2 could
      represent a growth advantage in prostate cancer.

PMID- 9253336
TI  - Body composition and physical fitness are major determinants of the growth
      hormone-insulin-like growth factor axis aberrations in adult Turner's syndrome,
      with important modulations by treatment with 17 beta-estradiol.
AB  - The objectives of this study were to 1) study the GH-insulin-like growth factor
      (IGF) axis in adult untreated Turner's syndrome compared to that in age-matched
      controls; 2) examine the effects of sex hormone substitution on this axis, 3)
      study the effects of route of administration of 17 beta-estradiol on the measured
      variables, and 4) examine the effects of sex steroids on hepatic function in
      Turner patients. Twenty-seven patients with Turner's syndrome were evaluated
      before and during sex hormone replacement, and an age-matched control group (n =
      24) was evaluated once. Main outcome variables were GH and other measures of the
      GH-IGF axis, body composition, maximal oxygen uptake, sex hormone-binding
      globulin, and hepatic enzymes and proteins. The integrated 24-h GH concentration
      (IC-GH; micrograms per L/24 h) was reduced in women with Turner's syndrome (T)
      compared to controls [C; mean +/- SD, 18.3 +/- 12.0 (T) vs. 37.2 +/- 29.7 (C); P
      = 0.007]. However, multiple regression revealed that fat-free mass (FFM) and
      maximal oxygen uptake were significant explanatory variables (joint r = 0.77; P <
      0.0005), accounting for 60% of the variance in the 24-h IC-GH. This association
      was also present in controls. After adjustment for these two variables, any
      difference in GH concentration between Turner patients and controls disappeared.
      Serum IGF-I and IGF-II were identical in Turner patients and controls despite the
      difference in 24-h IC-GH. The level of GH-binding protein (GHBP; nanomoles per L)
      was higher in Turner women [1.87 +/- 0.72 (T) vs. 1.22 +/- 0.33 (C); P = 0.0005];
      after adjustment for FFM, the difference in GHBP levels disappeared between
      Turner patients and controls. During sex hormone treatment a significant increase
      was seen in the 24-h IC-GH (P = 0.02), FFM (percentage of weight; P < 0.0005) and
      maximal oxygen uptake (milliliters of O2 per kg/min; P = 0.02). Serum IGF-I was
      unchanged, whereas serum IGF-II (micrograms per L) decreased significantly
      [Turner, basal (TB), vs. Turner, treatment (TT), 860 +/- 135 vs. 823 +/- 150; P =
      0.04]. Alanine aminotransferase (units per L), gamma-glutamyl transferase (units
      per L), and alkaline phosphatase (units per L) were significantly elevated during
      the basal study period, and all decreased during treatment [alanine amino
      transferase, 55 +/- 55 (TB) vs. 30 +/- 20 (TT; P = 0.006); gamma-glutamyl
      transferase, 92 +/- 98 (TB) vs. 43 +/- 65 (TT; P = 0.003); alkaline phosphatase,
      211 +/- 113 (TB) vs. 175 +/- 54 (TT); P = 0.06]. The route of administration of
      17 beta-estradiol did not affect its actions. In conclusion, we found the GH-IGF
      axis in Turner's syndrome to be normal, with body composition and physical
      fitness exerting the same modifying effects on this axis as seen in the normal
      population. Sex hormone replacement in Turner's syndrome is associated with
      normalizing effects on the GH-IGF axis, body composition, physical fitness, and
      hepatic function. The lowering of hepatic enzymes is a surprising and hitherto
      undiscovered action of sex steroids. Finally, the route of administration of 17
      beta-estradiol is of minor importance in Turner's syndrome.

PMID- 9253337
TI  - Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone
      (DHEA) in humans.
AB  - The physiological importance and therapeutical interest of dehydroepiandrosterone
      (DHEA) and its sulfate ester (DHEAS) are still controversial. Panhypopituitarism
      is characterized by the absence of secretion of adrenal and gonadal steroids and
      thus the production of their metabolites. The conversion of DHEA given orally
      into delta 5 derivatives, androgens, androgen metabolites, and estrogens was
      studied in ten patients with complete panhypopituitarism. Sex steroid therapy was
      withdrawn for at least 2 months. Each patient received, at 1-month intervals and
      in a random order, two single oral doses of DHEA (50 mg and 200 mg) and placebo.
      During each treatment, urine samples were collected for 24 h, and blood samples
      were drawn at hourly intervals for 8 h. In patients with pituitary deficiency,
      plasma DHEA and DHEAS were not detectable and increased, with the 50 mg dose, up
      to levels observed in young adults. The administration of 200 mg of DHEA induced
      an increase of both steroids to supraphysiological plasma levels. A small
      increase of delta 5-androstenediol was observed. In contrast, the increase of
      plasma delta 4-androstenedione was important and dose dependent. DHEA was also
      converted into the potent sex steroid testosterone (T). The administration of a
      50 mg dose of DHEA restored plasma T to levels similar to those observed in young
      women. The 200 mg dose induced an important increase of plasma T, slightly below
      the levels observed in normal men. The increase of plasma dihydrotestosterone
      levels was small at both doses of DHEA, in contrast with the large conversion of
      DHEA into androsterone glucuronide and androstanediol glucuronide. Finally, DHEA
      administration induced a significant and dose dependent increase of plasma
      estrogens and particularly of estradiol. In conclusion, this short term study
      demonstrates that: 1) panhypopituitarism is a model of interest to study the
      metabolism of DHEA; 2) in the absence of pituitary hormones and of adrenal and
      gonadal steroids, DHEA given orally is mainly converted into delta 4 derivatives,
      which in turn are strongly metabolized into 5 alpha-3keto-reduced steroids; 3) a
      significant increase of sex active hormones was observed in plasma after 200 and
      even 50 mg of DHEA. Thus, biotransformation of DHEA into potent androgens and
      estrogens may explain several of the reported beneficial actions of this steroid
      in aging people.

PMID- 9253338
TI  - Phe576 plays an important role in the secondary structure and intracellular
      signaling of the human luteinizing hormone/chorionic gonadotropin receptor.
AB  - Recent studies have identified multiple activating mutations in the sixth
      transmembrane domain of LH/chorionic gonadotropin receptor (LH/CGR) in patients
      with male-limited precocious puberty. Computer analysis suggested that these
      mutations had an effect on the secondary structure of the third cytoplasmic loop
      and sixth transmembrane domain, and that Phe576 was a critical conformational
      bridging residue between these regions that might be important for receptor
      activity. We made four amino acid substitutions of the Phe576 (F576I, F576G,
      F576Y, F576E) in the LH/CG receptor to analyze its functional role. Computer
      analysis of secondary structure predicted that the F576E mutant changed the
      secondary structure to a totally helical conformation in the region of the third
      intracellular and sixth transmembrane domain. In contrast, the F576G, F576I, and
      F576Y mutants were predicted to change the helical conformation in the region to
      an extended conformation. In expression studies, mutations of Phe576 produced
      functional changes in cAMP and inositol phosphate (IP) signaling, and human CG
      (hCG) binding. Mutations predicted to cause an extended conformation exhibited
      two functional patterns: first, constitutively activating in cAMP signaling
      without changes in IP signaling or hCG binding (F576I and F576G), and second,
      constitutively activating in cAMP signaling with decreased hCG-induced cAMP and
      IP signaling and with both higher affinity and lower capacity of hCG binding
      (F576Y). The mutation predicted to cause a totally helical conformation resulted
      in no cAMP response and a minimal IP response to hCG stimulation, with negligible
      hCG binding (F576E). These data suggest that the common change induced by the
      F576I, F576G, and F576Y mutations to an extended conformation on the third
      cytoplasmic loop and sixth transmembrane domain of the LH/CGR results in
      increased Gs coupling and activation of adenylyl cyclase. The F576Y mutation
      appears to have an additional effect, beyond a modification in receptor
      conformation, that leads to higher affinity and lower capacity of hCG binding, as
      well as altered Gq coupling and phospholipase C activation. The F576E mutation
      has a distinct and different impact on receptor conformation, which leads to
      negligible hCG binding and minimal function; however, the F576E mutation may
      provide a clue to understanding the receptor mutations that result in loss of
      function and pseudohermaphroditism. We conclude that Phe576 plays an important
      role in the human LH/CGR with respect to receptor conformation, Gs coupling, and
      cAMP signaling consistent with predictions from mutations associated with male
      limited precocious puberty.

PMID- 9253339
TI  - Minimal cardiac effects in asymptomatic athyreotic patients chronically treated
      with thyrotropin-suppressive doses of L-thyroxine.
AB  - Biondi, Fazio, and colleagues recently reported that long term T4 treatment to
      suppress serum TSH markedly affects cardiac function. T4-treated patients had
      more symptoms [12.2 +/- 3.9 (+/-SD) vs. 4.2 +/- 2.3 by quantitative
      questionnaire], higher mean heart rate, increased incidence of atrial
      extrasystoles, increased interventricular septal thickness and left ventricular
      mass index (LVMi), and significant diastolic dysfunction. The severity of cardiac
      abnormalities was highly correlated with scores of a rating scale used for
      assessing symptoms of thyrotoxicosis. We have duplicated their studies in 17
      athyreotic patients (mean age, 45 +/- 10 yr; range, 27-63 yr) without heart
      disease or hypertension whose dose of T4 was titrated to suppress serum TSH to
      less than 0.01 microU/mL. The mean duration of T4 treatment was 9.2 +/- 5.4 yr.
      Controls were healthy volunteers matched for sex and age (+/-3 yr). The mean T4
      dose was 2.8 +/- 0.9 micrograms/kg (0.192 +/- 0.058 mg/day). By questionnaire,
      patients had minimal symptoms, although their symptom score was significantly
      greater than the control value (4 +/- 3 vs. 2 +/- 1; P < 0.05; maximum score,
      36). No differences in mean heart rate or in atrial or ventricular extrasystoles
      were noted. In patients, indexes of systolic and diastolic function and
      interventricular septal thickness were similar to control values. The mean LVMi
      was normal in both groups. However, the mean LVMi in patients (117 +/- 35 g/m2)
      was higher than that in controls (92 +/- 31; P < 0.05). In conclusion, patients
      were minimally affected by TSH-suppressive doses of T4. They had few symptoms and
      no increase in extrasystoles or basal heart rate. Based on current knowledge, the
      increase in LVMi observed in patients without associated significant systolic or
      diastolic abnormalities does not have clinical or prognostic importance.
      Therefore, in the absence of symptoms of thyrotoxicosis, patients treated with
      TSH-suppressive doses of L-T4 may be followed clinically without specific cardiac
      laboratory studies.

PMID- 9253340
TI  - Comparative messenger ribonucleic acid analysis of immediate early genes and sex
      steroid receptors in human leiomyoma and healthy myometrium.
AB  - To shed light on the molecular mechanisms involved in the pathogenesis of uterine
      leiomyomas, transcript levels of the immediate early genes c-fos, c-myc, and c
      jun and of the estrogen receptor (ER) and progesterone receptor (PR) were
      determined in tissue samples of human myometrium and leiomyoma. The messenger RNA
      (mRNA) content was analyzed by RT-PCR. mRNAs for c-fos, c-myc, c-jun, ER, and PR
      were detected in all 18 samples of leiomyoma and corresponding myometrial tissue
      collected in this study. Interestingly, in contrast to healthy tissues, we found
      a distinct and significant reduction of c-fos mRNA in the tumor. These data were
      substantiated by the finding of lowered c-Fos protein levels in leiomyomas
      tissues. Moreover, transcripts of c-jun and c-myc were less abundant in most of
      the leiomyomas than in the myometrium. This different expression of the
      protooncogenes in leiomyomas and myometrium was independent of the phase of the
      menstrual cycle in which samples were collected. In contrast to the reduced
      transcript levels observed for the immediate early genes, the ER and PR mRNA
      contents of the leiomyomas and myometrium did not differ. These results were
      confirmed by immunohistochemical studies for ER and PR protein. In conclusion,
      our data show that the deregulated expression of protooncogenes, especially of c
      fos, is linked to the pathogenesis of leiomyomas. Confirmation of a potential
      role of downregulated c-fos levels for the benign character of these tumors
      requires further investigation. Additionally, the findings suggest that sex
      steroids do not influence the different expression patterns of c-fos, c-myc, and
      c-jun in leiomyomas, as compared with myometrium.

PMID- 9253341
TI  - Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal
      axis responsivity in healthy humans.
AB  - The hypercortisolism of melancholic depression is thought to reflect hypothalamic
      hypersecretion of CRH and may be related to the hyperarousal associated with this
      syndrome. Although chronic administration of imipramine to experimental animals
      significantly decreases CRH messenger RNA levels in the paraventricular nucleus,
      it is generally thought that resolution of hypercortisolism following recovery
      from depression is related to the improvement in mood and decrease in anxiety
      that accompanies recovery rather than an intrinsic effect of imipramine. The
      present study was designed to explore whether chronic imipramine administration
      to healthy, nondepressed volunteers is associated with effects on hypothalamic
      pituitary-adrenal (HPA) axis function. We studied basal and provocative measures
      of HPA axis function in 14 healthy volunteers before and after 6 weeks of
      imipramine treatment at therapeutic doses. Imipramine was associated with
      decreased responses in peak ACTH and cortisol to ovine CRH and in peak ACTH to
      arginine vasopressin (P = 0.02, P = 0.003, and P = 0.02, respectively) without
      changes in indices of basal HPA axis function. These data are consistent with
      preclinical findings and support the hypothesis that imipramine has an intrinsic
      effect on central components of HPA axis function, potentially related to its
      therapeutic effects.

PMID- 9253342
TI  - Embryonic regulation of integrins beta 3, alpha 4, and alpha 1 in human
      endometrial epithelial cells in vitro.
AB  - In the present study, we examined the embryonic regulation of beta 3 integrin in
      human endometrial epithelial cells (EEC) at the protein level and analyzed
      putative embryonic factors responsible for this regulation. The model employed is
      based on a clinical in vitro fertilization program in which single human embryos
      were cocultured with EEC until blastocyst stage and then transferred back to the
      uterus. After embryo transfer, EEC wells were divided according to the embryonic
      status reached: EEC with embryos that achieved the blastocyst stage, EEC with
      arrested embryos, and EEC without embryos. Immunostaining for beta 3 was positive
      in plasma membrane of EEC. Flow cytometry showed a mean percentage of beta 3
      stained cells of 24.1 +/- 5.7 in EEC cocultured with embryos that achieved the
      blastocyst stage (n = 13) vs. 9.5 +/- 1.6 (P < 0.05) in those EEC cultured with
      arrested embryos (n = 12). Immunostaining for alpha 1 and alpha 4 integrins was
      negative in EEC monolayers studied, regardless of the presence or absence of
      embryos, and these findings were confirmed by flow cytometry. The possibility
      that the embryonic IL-1 system and leukemia inhibitory factor were involved in
      the endometrial beta 3 up-regulation was investigated by neutralizing experiments
      demonstrating a significant inhibition of beta 3-stained cells when EEC
      monolayers were cultured in the presence of EEC/blastocyst-conditioned media with
      (n = 4) vs. without (n = 8) antihuman interleukin (IL)-1 alpha + IL-1 beta (1.65%
      vs. 14.6%; P < 0.05). Dose-response experiments further demonstrated an up
      regulation of beta 3 positive cells when IL-1 alpha + IL-1 beta were added to the
      medium at a concentration of 10 pg/mL compared with control medium without added
      cytokines (40% vs. 20%, n = 4). The functional relevance of the EEC beta 3 up
      regulation was tested using a mouse blastocyst adhesion assay. More mouse
      blastocysts attached to EEC previously in contact with human blastocyst (72.7%)
      compared with those EEC previously in contact with arrested embryos (40%). Our
      results demonstrate the selective effect of a developing human embryo on EEC
      expression of beta 3, which is maximal when a human blastocyst instead of an
      arrested embryo is considered. Furthermore, the embryonic IL-1 system seems to be
      involved in the EEC beta 3 up-regulation, reinforcing the concept of precise
      paracrine cross-talk between blastocyst and endometrial epithelium during
      embryonic implantation.

PMID- 9253343
TI  - Circulating concentrations of dimeric inhibin A and B in the male rhesus monkey
      (Macaca mulatta).
AB  - The purpose of this study was to determine the relative concentrations of inhibin
      A and B in peripheral serum of the adult male rhesus monkey and to examine the
      testicular contribution to these circulating forms of inhibin. In addition,
      inhibin B concentrations were also determined in peripheral sera of neonatal and
      juvenile males and in spermatic vein blood of adults. Immunoradiometric assays
      specific for the measurement of inhibin A and B were used. These assays also
      provided an opportunity to reexamine the physiological significance of a
      replacement infusion of recombinant human (rh)-inhibin A previously employed to
      study the role of this hormone in regulating FSH secretion in the monkey. In
      intact adults, the mean (+/-SE) serum concentration of inhibin B was 1008 +/- 184
      pg/mL. In contrast, circulating inhibin A concentrations were very low (< 46
      pg/mL). Inhibin B was consistently detected in neonatal monkey serum (275 +/- 57
      pg/mL), and concentrations of this inhibin dimer increased throughout postnatal
      development, reaching maximum values in adulthood. Circulating inhibin A
      concentrations in neonatal and juvenile monkeys were undetectable (< 7 pg/mL).
      Both forms of inhibin were generally undetectable in castrate sera. The ratio of
      inhibin B concentrations in testicular venous blood to those in the peripheral
      circulation was 1.4:1. These findings indicate that, in the male monkey, inhibin
      B is the principal form of circulating dimeric inhibin, and that this hormone is
      derived exclusively from the testis. The elevated levels of circulating inhibin B
      in the juvenile male monkey suggest that, during this phase of development,
      testicular inhibin B secretion is relatively gonadotropin independent.
      Additionally, we found that the concentration of circulating inhibin A in
      castrate animals that had earlier received an iv infusion of rh-inhibin A (832
      ng/h/kg BW) was 9881 +/- 2135 pg/mL, indicating that this mode of inhibin
      replacement may not have been entirely physiological.

PMID- 9253344
TI  - Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with
      neuron-specific enolase and the alpha-subunit of glycoprotein hormones.
AB  - Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine
      tumors. Its specificity in differentiating between neuroendocrine and
      nonneuroendocrine tumors, its sensitivity to detect small tumors, and its
      clinical value, compared with other neuroendocrine markers, have not clearly been
      defined, however. The objectives of this study were to evaluate the clinical
      usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron
      specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU)
      were determined in 211 patients with neuroendocrine tumors and 180 control
      subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU
      were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors,
      respectively. Serum CgA was most frequently increased in subjects with
      gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%),
      nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid
      carcinomas (50%). The highest levels were observed in subjects with carcinoid
      tumors. NSE was most frequently elevated in patients with small cell lung
      carcinoma (74%), and alpha-SU was most frequently elevated in patients with
      carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had
      elevated CgA concentrations. A significant positive relationship was demonstrated
      between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated
      concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%,
      and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300
      micrograms/L, were observed in only 2% of control patients (n = 3) compared to
      40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the
      best general neuroendocrine serum marker available. It has the highest
      specificity for the detection of neuroendocrine tumors compared to the other
      neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated
      with tumor volume; therefore, small tumors may go undetected. Although its
      specificity cannot compete with that of the specific hormonal secretion products
      of most neuroendocrine tumors, it can have useful clinical applications in
      subjects with neuroendocrine tumors for whom either no marker is available or the
      marker is inconvenient for routine clinical use.

PMID- 9253345
TI  - Variants in the human intestinal fatty acid binding protein 2 gene in obese
      subjects.
AB  - Fatty acid binding protein 2 gene (FABP2) has been proposed to be an important
      candidate gene for insulin resistance; therefore, it also could be a promising
      candidate gene for obesity. We screened the whole coding region of the FABP2 gene
      in 40 obese nondiabetic Finnish subjects. Furthermore, we investigated the
      effects of the codon 54 polymorphism of this gene (Ala-->Thr) on insulin levels
      and basal metabolic rate in 170 obese subjects. The frequencies of the variants
      found in exon 4 (GTA-->GTG) and 3'-noncoding region (GCGCA-->GCACA), as well as
      the allele frequencies for the variable lengths of the ATT repeat sequence in
      intron 2 did not differ between the obese subjects and nonobese controls. The
      frequency of threonine-encoding allele in codon 54 of the FABP2 gene did not
      differ between obese and control subjects (28 vs. 29%, respectively). In the
      obese group there were no differences in gender distribution, age, weight, body
      mass index, lean body mass, percentage of body fat, waist circumference, and
      waist-to-hip ratio among the individuals homozygous for Ala54, heterozygous for
      Thr54, and homozygous for Thr54-encoding alleles. Similarly, fasting serum
      insulin, glucose, lipids and lipoprotein concentrations, basal metabolic rate
      (adjusted for lean body mass and age), respiratory quotient, and rates of glucose
      and lipid oxidation did not differ among the groups. We conclude that obesity is
      not associated with specific variants in the FABP2 gene. Furthermore, the codon
      54 Ala to Thr polymorphism of this gene does not influence insulin levels or
      basal metabolic rate in obese Finns.

PMID- 9253346
TI  - Growth inhibition of new human thyroid carcinoma cell lines by activation of
      adenylate cyclase through the beta-adrenergic receptor.
AB  - In normal thyroid cells, the TSH-adenylate cyclase system plays a pivotal role in
      controlling growth and differentiation. However, the role of this system in the
      growth of thyroid carcinoma is not well understood. To investigate this subject,
      we have established four new human thyroid carcinoma cell lines, designated BHP 2
      7, 7-13, 10-3, and 18-21, from different patients. Northern gel analysis revealed
      that all of these cell lines expressed Pax-8 messenger ribonucleic acid;
      additionally, only BHP 18-21 cells expressed TTF-1 messenger ribonucleic acid.
      These cells were treated with various concentrations of 8-bromo-cAMP, forskolin,
      TSH, and adrenergic receptor agonist (norepinephrine, epinephrine, and
      isoproterenol). Cell proliferation was assessed by [3H]thymidine incorporation
      and cell number. In these human thyroid carcinoma cell lines, the addition of 8
      bromo-cAMP reduced [3H]thymidine incorporation at a concentration of 10 mumol/L.
      Forskolin (0.1-10 mumol/L) significantly induced cAMP accumulation, decreased
      [3H]thymidine incorporation, and reduced cell number in a dose-dependent manner.
      Conversely, TSH (0.01-1 mU/ mL) did not affect the accumulation of cAMP or cell
      growth. We found that adrenergic receptor agonists induced the accumulation of
      cAMP and inhibited cell growth. The rank of potency was isoproterenol >
      epinephrine > > norepinephrine. The binding studies of [3H]CGP-12177, a specific
      beta-adrenergic agonist, revealed that these new thyroid carcinoma cells had beta
      adrenergic receptors. These results indicate that cAMP inhibits the growth of
      some human thyroid carcinoma cells, and that cAMP production is regulated through
      beta-adrenergic receptor-mediated pathways, but not through TSH receptor-mediated
      pathways.

PMID- 9253347
TI  - Immunoglobulin G kappa antithyroid peroxidase antibodies in Hashimoto's
      thyroiditis: epitope-mapping analysis.
AB  - Patients with autoimmune thyroid disease frequently have high affinity antibodies
      to thyroid peroxidase (TPO), although the role they play in disease pathogenesis
      is not known. We have previously prepared 37 monoclonal anti-TPO IgG kappa Fab
      fragments from two patients with Hashimoto's thyroiditis and demonstrated the
      similarity of these Fab sequences to those published previously, mainly derived
      from patients with Graves' disease. In this paper, we described epitope mapping
      of these Fabs using a previously characterized panel of murine monoclonal
      antibody (mAb) and show that the Fabs bind to two neighboring epitopes on native
      TPO. Although the epitope-mapping method differs from that used to characterize
      previously published TPO-reactive Fab sequences, it indicates a similarly
      restricted response to neighboring epitopes in both Graves' disease and
      Hashimoto's thyroiditis. The epitope mapping included mAb 47, which binds to a
      linear TPO peptide of known sequence in addition to native TPO. Although TPO
      reactive Fab did not inhibit the binding of mAb 47, mAb 47 did inhibit the
      binding of Fab, indicating the likely site of the immunodominant region on native
      TPO. These results confirm the restricted nature of TPO antibody and further
      delineate the immunodominant region of native TPO as defined by the mAb.

PMID- 9253348
TI  - Frequency modulation of follicle-stimulating hormone (FSH) during the luteal
      follicular transition: evidence for FSH control of inhibin B in normal women.
AB  - To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the
      effect of differing levels of FSH on inhibin B secretion during the luteal
      follicular transition, exogenous GnRH was administered to GnRH-deficient women
      using one of two regimens, and the results were compared to those in normal
      women. In the GnRH-deficient women, the GnRH pulse frequency was increased from
      every 4 h in the late luteal phase to every 90 min on the day of menses to mimic
      normal cycling women (physiological frequency transition; n = 8 studies) or the
      GnRH pulse frequency was kept constant at a late luteal phase frequency of every
      4 h through the first 6 days of the subsequent early follicular phase of cycle 2
      (slow frequency transition; n = 6 studies). The differential rise in FSH
      secretion induced in these studies allowed us to examine the subsequent
      contribution of varying levels of FSH to inhibin B secretion. A physiological
      regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH
      and inhibin B levels that did not differ from that in normal cycling women and a
      normal follicular phase length. On the other hand, maintaining a luteal frequency
      of GnRH for 6 days into the subsequent early follicular phase produced FSH levels
      significantly lower than those in the physiological transition (P < 0.05), with
      the greatest difference seen on the day after menses (9.1 +/- 1.0 vs. 16.4 +/-
      1.4 IU/L for the slow and physiological transition groups, respectively; P <
      0.005), but no difference in LH. This slower rise of FSH secretion in the slow
      frequency group was associated with significantly lower inhibin B levels (43.3 +/
      21.5 vs. 140.0 +/- 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later
      doubling of estradiol from baseline (day 9.6 +/- 0.9 vs. day 5.6 +/- 0.1; P <
      0.02), and a longer follicular phase length (16.0 +/- 1.4 vs. 11.6 +/- 0.9 days;
      P < 0.05) compared with those in the physiological transition group. In
      conclusion, during the luteal-follicular transition, the GnRH pulse frequency
      contributes to but is not solely responsible for the FSH rise that initiates
      folliculogenesis. Alteration of FSH dynamics induced by changes in GnRH pulse
      frequency in GnRH-deficient women provides evidence that FSH stimulates inhibin B
      production in the human. Timely follicular development indicated by both
      estradiol and inhibin B secretion appears to be dependent on the pattern of
      increase in FSH during the luteal-follicular transition.

PMID- 9253349
TI  - Fasting and postprandial lipid abnormalities in hypopituitary women receiving
      conventional replacement therapy.
AB  - Hypopituitary patients, particularly women, have excess mortality, mostly due to
      vascular disease. We have studied circulating lipid and lipoprotein
      concentrations, fasting and over 24 h, in hypopituitary women and men and in
      matched controls. Firstly, 67 hypopituitary patients (36 women) and 87 normal
      controls (54 women) were studied after an overnight fast. Secondly, 12 patients
      (6 women) and 14 matched controls (7 women) were studied over 24 h of normal
      meals and activity. The patients were all GH deficient and were replaced with
      cortisol, T4, and sex hormones where appropriate, but not with GH. In the first
      study, circulating triglycerides, total cholesterol, high density lipoprotein
      (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol were measured
      after an overnight fast. In the second study, fasting levels of apolipoprotein B,
      apolipoprotein A1, and lipoprotein(a) were also measured, and then circulating
      triglyceride and total cholesterol concentrations were measured over 24 h.
      Fasting concentrations of triglyceride (mean +/- SEM, 1.73 +/- 0.22 vs. 1.11 +/-
      0.09 mmol/L; P = 0.0025), total cholesterol (6.45 +/- 0.25 vs. 5.59 +/- 0.21
      mmol/L; P = 0.002), LDL cholesterol (4.58 +/- 0.24 vs. 3.80 +/- 0.19 mmol/L; P =
      0.007), and apolipoprotein B (135 +/- 10 vs. 111 +/- 9 mg/dL; P = 0.048) were
      elevated in hypopituitary compared to control women. The lipid alterations were
      observed in older and younger women and occurred independently of sex hormone or
      glucocorticoid replacement. Fasting values were not significantly different in
      hypopituitary and control men. Patients and controls (women and men) had similar
      fasting HDL cholesterol, apolipoprotein A1, and lipoprotein(a) concentrations.
      Although the differences that existed in fasting lipid values were most marked in
      women, the men were also abnormal in this respect, in that a higher proportion of
      hypopituitary than control men had total and LDL cholesterol above recommended
      values (> or = 6.2 and > or = 4.1 mmol/L, respectively). In the postprandial
      period (0730-2030 h), the areas under the curve (AUC) for circulating
      triglyceride and total cholesterol were significantly higher in hypopituitary
      than control women (P = 0.0089 and P = 0.0016, respectively). The AUC for
      triglyceride and total cholesterol over 24 h were also significantly increased (P
      = 0.009 and P = 0.0004, respectively). No significant differences were observed
      for postprandial and 24-h AUC for triglyceride and total cholesterol
      concentrations in men. We conclude that hypopituitarism with conventional
      replacement therapy is associated with unfavorable fasting and postprandial lipid
      and lipoprotein concentrations, particularly in women. The changes may contribute
      to the observed increased vascular morbidity and mortality.

PMID- 9253350
TI  - Mechanisms of defective glucose-induced insulin release in human pancreatic
      islets transplanted to diabetic nude mice.
AB  - We have previously observed that human islets, transplanted under the kidney
      capsule of hyperglycemic nude mice, show a longlasting impairment in glucose
      induced insulin release. To investigate the cause(s) of this phenomenon, we
      transplanted human islets into normoglycemic or alloxan-diabetic nude mice for a
      4- to 6-week period. In a third experimental group, aimed at evaluating
      reversibility of hyperglycemia effects, diabetic nude mice bearing a human islet
      graft were cured by a second intrasplenic transplant of mouse islets, and the
      human islets were exposed to a further 2 weeks of normoglycemia. Four to 6 weeks
      of hyperglycemia induced a severe impairment of glucose- and arginine-induced
      insulin release, as demonstrated by perfusion of the graft-bearing kidney. This
      defective release was not restored by a subsequent 2-week period of
      normoglycemia, and it was accompanied by normal (pro)insulin biosynthesis,
      glucose oxidation, and expression of insulin messenger RNA. Taken together with
      our previous study, these observations indicate that impaired glucose metabolism,
      depletion of insulin messenger RNA, decreased (pro)insulin biosynthesis,
      increased glycogen accumulation, and depletion of insulin reserves cannot explain
      the deleterious effects of the diabetic state on human islet insulin release.
      This, and the similar inhibition of glucose- and arginine-induced insulin
      release, suggest that prolonged hyperglycemia may exert its deleterious effect on
      insulin release at a step distal to closure of ATP-sensitive K-channels.

PMID- 9253351
TI  - Human B cells secreting immunoglobulin G to glutamic acid decarboxylase-65 from a
      nondiabetic patient with multiple autoantibodies and Graves' disease: a
      comparison with those present in type 1 diabetes.
AB  - Antibodies to glutamic acid decarboxylase-65 (GAD65) are present in a number of
      autoimmune disorders, such as insulin-dependent (type 1) diabetes mellitus
      (IDDM), stiff man syndrome, and polyendocrine autoimmune disease. Antibodies to
      GAD in IDDM patients usually recognize conformation-dependent regions on GAD65
      and rarely bind to the second isoform, glutamic acid decarboxylase-67 (GAD67). In
      contrast, those present in stiff man syndrome and polyendocrine disease commonly
      target the second isoform (GAD67) and include antibodies that are less dependent
      on the conformation of the molecule. By immortalizing peripheral blood B cells
      with Epstein-Barr virus, we have generated three human IgG autoantibodies, termed
      b35, b78, and b96, to GAD65 from one patient with multiple autoantibodies to
      endocrine organs and Graves' disease. All three autoantibodies are of the IgG1
      isotype, with islet cell activity, and do not react with GAD67. The regions on
      GAD65 recognized by the three autoantibodies have been investigated by
      immunoprecipitation with a series of chimeras, by binding to denatured and
      reduced antigens, and using protein footprinting techniques. Using chimeric GAD
      proteins, we have shown that b35 targets the IDDM-E1 region of GAD65 (amino acids
      240-435) whereas both b78 and b96 target the IDDM-E2 region of GAD65 (amino acids
      451-570). Furthermore, examination of binding to recombinant GAD65 and GAD67 by
      Western blotting revealed some differences in epitope recognition, where only b78
      bound denatured and reduced GAD65. However, b35, b78, and b96 autoantibodies had
      different footprinting patterns after trypsin treatment of immune complexes with
      GAD65, again indicating different epitope recognition. Our results indicate that
      antibodies to GAD65 present in nondiabetic patients with multiple autoantibodies
      to endocrine organs show similarities to those in IDDM (by targeting IDDM-E1 and
      IDDM-E2 regions of GAD65) as well as subtle differences in epitope recognition
      (such as binding to denatured and reduced GAD65 and by protein footprinting).
      Thus, the GAD65 epitopes recognized by autoantibodies in different autoimmune
      diseases may overlap and be more heterogeneous than previously recognized.

PMID- 9253352
TI  - Growth hormone receptor messenger ribonucleic acid in normal and pathologic human
      adrenocortical tissues--an analysis by quantitative polymerase chain reaction
      technique.
AB  - GH receptor (GHR) has been reported to express in both normal rat and human
      adrenals. However, no study examined GHR expression in diseased human adrenal
      cortex. We quantitated, with RT-PCR, GHR messenger RNA (mRNA) in both normal and
      diseased human adrenal cortex with the following results: GHR mRNA levels in four
      histologically normal, not steroid-stimulated, control adrenal cortices was 1.5
      11 x 10(4) molecules/microgram total RNA; in three diffusely hyperplastic
      adrenals (DH): 6.7-17.7 x 10(4); in two nonfunctioning tumors (NF): 0.84-1.9 x
      10(4); in five androgen-producing neoplasms (AP): 4.6-34 x 10(4); and in five
      glucocorticoid-producing neoplasms (GP): 6.7-87 x 10(4). GHR transcript levels
      among adrenal cortices, DH, NF, AP, and GP reached statistically significant
      difference (P < 0.03). The GP group exhibited higher GHR mRNA levels than
      controls (P < 0.006). NF, as well as GP and AP, tumors had less GHR mRNA than
      their histologically normal adjacent cortex (P < 0.05). A positive correlation
      between urinary cortisol and GHR messenger RNA (mRNA) levels from GP and DH was
      observed (r = 0.93, P < 0.003). Our data suggest that GHR is expressed in both
      normal and diseased adrenal cortex and that GHR mRNA accumulation is less
      efficient in adrenocortical neoplasm than their adjacent nonneoplastic cortex.
      GHR expression in adrenal cortex provides an evidence of direct GH action in this
      tissue.

PMID- 9253353
TI  - Influence of circulating epinephrine and norepinephrine on insulin-like growth
      factor binding protein-1 in humans.
AB  - The aim of the present study was to investigate the influence of circulating
      epinephrine (Epi) and norepinephrine (Norepi) on serum insulin-like growth factor
      binding protein-1 (IGFBP-1) concentrations. Healthy men received 0.3 nmol.kg.min
      Epi iv (n = 6), 0.5 nmol.kg.min Norepi iv (n = 7), or saline (n = 5) during 30
      min. Arterial blood samples were obtained before, during, and 120 min after
      infusion. During the catecholamine infusion arterial Epi and Norepi plasma
      concentrations reached 6.35 +/- 0.53 and 15.65 +/- 2.71 nmol/L, respectively,
      which resulted in significant increases in glucose concentrations. When Epi was
      infused, IGFBP-1 increased from 45 +/- 6 micrograms/L to 76 +/- 10 micrograms/L
      (P < 0.05) 60 min after the infusion. Epi was also followed by increases in
      insulin, C-peptide, and glucagon. Norepi resulted in a slight increase in
      circulating IGFBP-1 (43 +/- 6 to 54 +/- 8 nmol/L, NS). The findings suggest that
      Epi, at plasma concentrations similar to those reached during physical stress,
      stimulates the production of IGFBP-1 in humans.

PMID- 9253354
TI  - Analysis of proliferative activity of the parathyroid glands using proliferating
      cell nuclear antigen in patients with hyperparathyroidism.
AB  - To elucidate the cellular proliferative kinetics of the parathyroidal gland in
      patients with hyperparathyroidism, we investigated the expression of
      proliferating cell nuclear antigen (PCNA) in parathyroidal tissues using an
      immunohistochemical procedure. The PCNA labeling index (LI; maximum LI, maximal
      stained area; average LI, evenly distributed stained area) indicating cellular
      proliferative activity was defined as the number of PCNA-positive cells per 1000
      parathyroid cells in the region of interest. We used these indexes to compare and
      investigate the proliferative activity of parathyroid cells under various
      conditions. The specimens used for the study were 42 parathyroid glands from 21
      patients with primary hyperparathyroidism (19 cases of adenoma and 2 cases of
      primary hyperplasia due to multiple endocrine neoplasia type 1) and 129
      parathyroid glands from 32 patients with secondary hyperparathyroidism. An
      additional 40 parathyroid glands resected during thyroid surgery of 30
      normocalcemic patients were used as normal controls. In normally functioning
      parathyroids, a small number of cells in the growth phase were found. In primary
      hyperparathyroidism, proliferative activity was highest in the adenoma followed
      by primary hyperplasia. In contrast, the PCNA LIs showed a low value in the
      normal rim of the adenoma and normal glands resected as biopsy specimens from
      adenoma patients. We, therefore, assumed that proliferative activity was
      suppressed in these cells compared with that in normally functioning glands. In
      secondary hyperparathyroidism, when the cell component of the parathyroid tissues
      was divided into five types, PCNA immunoreactivity was lowest in the dark chief
      cells. Proliferative activity in cells of the oxyphil series was the same or
      higher than that in the clear chief cells or vacuolated chief cells. When
      classified according to the structure of the parathyroid glands, cell
      proliferation was significantly higher in the nodular type than in the diffuse
      type (maximum LI, 176 +/- 231 vs. 38.3 +/- 55.7; average LI, 120 +/- 188 vs. 24.8
      +/- 43.5; mean +/- SD; P < 0.001). More PCNA-immunoreactive cells were found in
      autotransplanted glands with recurrence than in glands resected during the
      initial surgery. To summarize the PCNA expression classified according to the
      pathological types of hyperparathyroidism, the PCNA LIs were highest in secondary
      hyperplasia (maximum LI, 144 +/- 212; average LI, 96.0 +/- 169) and adenoma
      (maximum LI, 102 +/- 81.7; average LI, 67.5 +/- 67.7), followed by primary
      hyperplasia (maximum LI, 25.0 +/- 25.4; average LI, 19.2 +/- 22.2) and normal
      glands (maximum LI, 13.6 +/- 23.9; average LI, 4.40 +/- 8.90). These findings
      suggest that the cellular proliferative kinetics of the parathyroid gland differ
      depending on the type of hyperparathyroidism, glandular structure, and cell
      components. As the detection method of intranuclear expression of PCNA in cells
      is too sensitive, we should be careful not to overestimate the number of cells in
      the proliferative cycle. However, these results could not have been obtained
      using a conventional method such as DNA analysis by flow cytometry.

PMID- 9253355
TI  - The GLUT3 glucose transporter isoform is differentially expressed within human
      placental cell types.
AB  - The cellular localization of GLUT3 messenger ribonucleic acid (mRNA) and protein
      was examined in human term placenta using a combination of methodologies. In situ
      hybridization indicated that GLUT3 mRNA was present in the trophoblast cell layer
      and in vascular endothelium with a heterogeneous distribution pattern. GLUT3
      protein migrating at an apparent molecular mass of 49 kDa was detected by
      immunoblotting in membranes from whole placenta and endothelial cells derived
      from intraplacental microvessels, but not in isolated trophoblast cells. This
      cell-specific pattern of expression was confirmed by immunocytochemical studies
      showing a prominent localization of GLUT3 protein in vascular endothelium. These
      findings indicate a differential distribution of GLUT3 mRNA and protein in the
      human placenta. Based on its cell-specific distribution at the fetal interface,
      GLUT3 protein could be of cardinal importance in the transport of glucose from
      the placenta to the fetal circulation.

PMID- 9253356
TI  - Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs
      alpha genes as a cause of toxic thyroid adenomas.
AB  - A total of 33 different autonomous hot nodules from 31 patients, originating
      mainly from Belgium, were investigated for the presence of somatic mutations in
      the TSH receptor and Gs alpha genes. This constitutes an extension of our
      previous study, including the first 11 nodules of the series. The complete coding
      sequence of the TSH receptor gene and the segments of Gs alpha known to harbor
      mutations impairing guanosinetriphosphotase activity were studied by direct
      sequencing of genomic DNA extracted from the nodules. DNA from the juxtanodular
      tissue or peripheral white blood cells was analyzed in all patients to confirm
      that the mutations identified were somatic. Twenty-seven mutations (82%) were
      found in the TSH receptor gene, affecting a total of 12 different residues or
      locations. All these mutations but 2 (see below) have been identified previously
      as activating mutations. Only 2 mutations were found in Gs alpha (6%). In 4
      nodules, no mutation was detected. Five residues (Ser281, Ile486, Ile568, Phe631,
      and Asp633) were found mutated in 3 or 4 different nodules, making them hot spots
      for activating mutations. Phe631 and Asp633 belong to a cluster of 5 consecutive
      residues (629-633) in the N-terminal half of transmembrane segment VI; which
      harbor together 44% of the mutations identified in this cohort. Two novel
      mutations were identified: a point mutation causing substitution of Phe for Leu
      at position 629 (L629F); and a deletion of 12 bases removing residues 658-661 at
      the C-terminal portion of exoloop 3 (del658-661). When tested by transfection in
      COS-7 cells, both mutant receptors display increase in constitutive stimulation
      of basal cAMP accumulation. Although it is still capable of binding TSH, the
      del658-661 mutant has completely lost the ability to respond to the stimulation
      by the hormone. Our results demonstrate that, in a cohort of patients from a
      moderately iodine deficient area, somatic mutations increasing the constitutive
      activity of the TSH receptor are the major cause of autonomous hot nodules.

PMID- 9253357
TI  - An amphotropic retroviral vector expressing a mutant gsp oncogene: effects on
      human thyroid cells in vitro.
AB  - Point mutations of the gsp protooncogene (encoding the alpha-subunit of the Gs
      protein) that constitutively activate the cAMP signaling pathway are a common
      feature of and a plausible causative mechanism for thyroid hyperfunctioning
      adenomas (hot nodules). To investigate the extent to which mutant gsp acting
      alone can induce proliferation of thyroid follicular cells, we generated an
      amphotropic retroviral vector (based on the pBABE-neo plasmid and psi-CRIP
      packaging line) to permit stable introduction of a hemagglutinin-tagged Gln227-
      >Leu mutant gsp gene into normal human thyrocytes in vitro. The biological
      activity of the vector was confirmed by detection of HA-tagged Gsp protein
      expression and induction of cAMP synthesis in selected target cells. Normal human
      thyroid follicular cells in primary monolayer culture were infected with the gsp
      retroviral vector or with corresponding vectors expressing mutant H-ras or neo
      only as positive and negative controls, respectively. Although, as before, mutant
      ras generated 10-20 well differentiated epithelial colonies/dish of 10(5)
      infected cells, with an average lifespan of 15-20 population doublings, only
      small groups of no more than 15-50 differentiated thyrocytes were observed with
      the gsp vector. In addition to standard conditions (10% FCS), infections were
      performed in reduced serum (1% FCS, TSH, and insulin), in the presence of
      isobutylylmethylxanthine, or in the presence of agents capable of closing gap
      junctions, with no significant difference in outcome. Although little or no
      proliferative response was observed regardless of the conditions, there was clear
      evidence of morphological response (rearrangement of the actin cytoskeleton and
      increased cell size). The results suggest that gsp mutation may not be a
      sufficient proliferogenic stimulus by itself to account for hot nodule formation.

PMID- 9253358
TI  - Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the
      Ca(2+)-sensing receptor.
AB  - Activating mutations of the Ca(2+)-sensing receptor (CaR) gene have been
      identified in families with autosomal dominant hypoparathyroidism and in one
      patient with sporadic hypoparathyroidism. Here, we describe two additional
      patients with sporadic hypoparathyroidism. One patient presented with mild
      symptoms at age 18 yr; the other was severely symptomatic from infancy. A
      heterozygous missense mutation was identified in each patient. One mutation
      (L773R) involved the fifth transmembrane domain of the CaR, the other (N118K)
      affected the amino-terminal, extracellular domain. In both cases, the probands'
      parents lacked the mutation, indicating that the mutations arose de novo. In
      expression studies the mutations shifted the concentration-response curve to the
      left and increased maximal activity. We conclude that 1) sporadic
      hypoparathyroidism can be caused by de novo gain-of-function mutations of the
      CaR; 2) the phenotype can vary from mild to life-threatening hypocalcemia; 3)
      gain-of-function mutations can involve not only extracellular regions, as
      previously reported, but also transmembrane domains of the CaR; and 4) the
      mechanism of activation can involve both increased receptor sensitivity to Ca2+
      and increased maximal signal transduction.

PMID- 9253359
TI  - Two novel missense mutations in calcium-sensing receptor gene associated with
      neonatal severe hyperparathyroidism.
AB  - Familial hypocalciuric hypercalcemia (FHH) is characterized by lifelong
      asymptomatic hypercalcemia without PTH hypersecretion and is inherited as an
      autosomal dominant trait with near 100% penetrance. In contrast, neonatal severe
      hyperparathyroidism (NSHPT) is a life-threatening disorder characterized by
      marked hypercalcemia and PTH hypersecretion. FHH/NSHPT results from inactivating
      mutations of the human calcium-sensing receptor (Casr) gene on chromosome 3q13.3
      24. Nearly 30 different mutations of the Casr gene associated with FHH/NSHPT have
      been reported previously. In this report, genetic analysis of 1 Japanese NSHPT
      family revealed 2 novel mutations at codon 185 (CGA-->TGA/Arg-->Ter) in exon 4 of
      the Casr gene and at codon 670 (GGG-->GAG/Gly-->Glu) in exon 7. The Arg185Ter
      change was shown to occur in the proband's unaffected father and paternal
      grandmother as well as in the proband. The other mutation in exon 7 was shown in
      the proband's unaffected mother of Philippine origin as well as in the proband.
      This family is the first case of manifestation of more than 1 mutation in a
      proband's chromosomes; 1 mutation was obtained from the unaffected father, and
      the other was from the unaffected mother. Our observations have given us
      important keys to help elucidate the structure-function relationships of the
      Casr.

PMID- 9253360
TI  - Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF
      receptor, and CRF-binding protein and localization of the gene products in the
      human ovary.
AB  - Recently, the presence of immunoreactive corticotropin-releasing factor (IrCRF)
      in the thecal-stromal cells of the human ovary and the ability of CRF to suppress
      estrogen production by human granulosa cells in vitro have been reported. To
      understand the functional role of ovarian CRF requires characterization of the
      human ovarian CRF system, which includes CRF, type 1 CRF receptor (CRF-R1), and
      the high affinity CRF-binding protein (CRF-BP). Accordingly, we have examined the
      ovarian CRF system and the cellular distribution of these proteins and their
      messenger ribonucleic acids (mRNAs) using immunohistochemistry and in situ
      hybridization, respectively. Normal ovaries from 10 premenopausal women
      undergoing hysterectomy with ovariectomy were used in the analyses. IrCRF and its
      mRNA were localized in thecal cells of small antral and mature follicles. A low
      abundance of IrCRF and mRNA was also detected in stromal cells of both stages of
      follicles. Expression of the gene encoding CRF was more prominent in mature
      follicles than in small antral follicles. CRF-R1 mRNA signal was found
      exclusively in thecal cells of mature follicles and moderately in small antral
      follicles. Granulosa cells were devoid of CRF and CRF-R1 mRNAs and proteins. The
      IrCRF-BP, but not its transcript, was detected in thecal cells and luman of
      capillary vessels of the thecal/stromal compartment of mature follicles. The
      absence of CRF-BP gene transcript in human ovarian follicles was confirmed by
      reverse transcription-PCR, indicating that the IrCRF-BP detected is not derived
      from the ovarian transcript and suggesting that the presence of IrCRF-BP and
      luman of capillary vessels in the thecal compartment originates from the
      peripheral circulation. Thecal cells of mature follicles, relative to those of
      small antral follicles, exhibited an intensive immunostaining and mRNA signal for
      17 alpha-hydroxylase (P450c17) indicative of androgen biosynthesis. We conclude
      that the thecal compartment of the human ovary contains a CRF system endowed with
      CRF and CRF-R1 and the blood-derived CRF-BP. Granulosa cells are devoid of the
      CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17 alpha
      hydroxylase proteins and gene expression with follicular maturation suggest that
      the intraovarian CRF system may play an autocrine role in androgen biosynthesis
      with a downstream effect on estrogen production by the granulosa cells. The
      functionality of the ovarian CRF system may be conditioned by the relative
      presence of circulating CRF-BP by virtue of its ability to compete with CRF for
      the CRF receptor.

PMID- 9253361
TI  - Levels of hepatocyte growth factor and its messenger ribonucleic acid in
      uncomplicated pregnancies and those complicated by preeclampsia.
AB  - The purpose of this study was to elucidate the possible relationship between
      hepatocyte growth factor (HGF) expression and the pathogenesis of preeclampsia.
      The concentration of immunoreactive HGF was measured and the expression of HGF
      messenger ribonucleic acid (mRNA) assessed in human placentas obtained from two
      groups: uncomplicated and preeclamptic pregnancies at various gestational weeks.
      In addition, the localization of HGF mRNA and c-met protein was analyzed using in
      situ hybridization and immunohistochemical staining, respectively. The expression
      of HGF mRNA and the concentration of immunoreactive HGF were highest in second
      trimester and were significantly decreased in preeclamptic placentas compared
      with the uncomplicated cases in third trimester. HGF mRNA was localized to
      placental mesenchymal cells, whereas c-met protein was demonstrated on
      cytotrophoblast. These results provide evidence of an abnormality of HGF
      expression in the preeclamptic placentas. Such placentas exhibit the abnormally
      shallow trophoblast invasion of the uterus, and reduced expression of HGF could
      well account for this morphometric change.

PMID- 9253362
TI  - A growth hormone-releasing hormone-producing pancreatic islet cell tumor
      metastasized to the pituitary is associated with pituitary somatotroph
      hyperplasia and acromegaly.
AB  - The functional and morphological changes in the pituitary gland caused by a GHRH
      producing pancreatic islet cell tumor that metastasized to the pituitary and
      caused somatotroph hyperplasia are described. A 52-yr-old woman presented with
      loss of visual acuity, diabetes insipidus, and acromegaly caused by a GHRH
      producing endocrine carcinoma metastasized to the pituitary. The serum GHRH, GH,
      and insulin-like growth factor I levels of the patient were elevated.
      Immunohistochemical and in situ hybridization study revealed GHRH
      immunoreactivity and GHRH messenger RNA (mRNA) in the metastatic tumor cells. The
      anterior pituitary showed hyperplasia of somatotroph cells with intact acinar
      structure that did not contain an adenoma, determined by light microscopy using
      silver impregnation. Electron microscopy revealed hyperplastic characteristics of
      densely granulated somatotrophs. In situ hybridization documented strong signals
      for GH mRNA and pituitary-specific transcriptional factor Pit-1 mRNA in the
      hyperplastic somatotrophs. A weak signal for GHRH receptor mRNA was detected in
      these somatotrophs. However, using in situ RT-PCR, GHRH receptor mRNA was more
      conclusively observed in most of the somatotrophs. The excessive production of
      GHRH by metastatic tumor may have resulted in somatotroph hyperplasia by the
      synergistic effects of Pit-1 and GHRH receptor. It can be concluded that the
      pathogenesis of pituitary adenoma formation is primarily mediated by other
      factors than hypothalamic hormone.

PMID- 9253363
TI  - Differential expression of members of the bcl-2 gene family in proliferative and
      secretory human endometrium: glandular epithelial cell apoptosis is associated
      with increased expression of bax.
AB  - Glandular epithelial cells of the human endometrium initiate apoptosis in the
      secretory phase of the cycle. To better understand the regulation of apoptosis in
      this paradigm of endocrine-regulated cell turnover, we studied the expression of
      the cell death regulatory genes, bax, bcl-2, and bcl-x, in human proliferative
      and secretory endometria relative to the absence or presence of apoptosis. As
      assessed by immunohistochemistry, levels of BAX protein were modest in
      proliferative endometrium and increased dramatically in the secretory phase when
      apoptosis was most prevalent. Expression of BAX was predominantly localized to
      epithelial cells of the functionalis layer of the secretory endometrium. In
      contrast, BCL-2 immunoreactivity was maximal during the proliferative phase and
      decreased in the secretory phase. Moreover, BCL-2 was topographically
      concentrated in the basalis layer. Immunoreactive BCL-X protein was observed
      mostly in glandular epithelial cells of the human endometrium. Compared with
      proliferative endometrium, secretory endometrium showed stronger BCL-X staining,
      especially in the functionalis layer. By Western blotting we confirmed that both
      proliferative and secretory endometrium expressed the long or antiapoptosis form
      as well as the short or proapoptosis form of the BCL-X protein. Taken together,
      our results demonstrate a coordinated pattern of expression of bcl-2 gene family
      members in human endometrium during the menstrual cycle, with a shift toward
      greater levels of the proapoptosis protein, BAX, occurring in glandular
      epithelial cells during the secretory phase of the cycle. Therefore, we conclude
      that cyclic changes in endometrial growth and regression may be precisely
      regulated by shifts in the ratio or balance of BCL-2 and related proteins in
      glandular epithelial cells.

PMID- 9253364
TI  - Plasma leptin levels do not change in patients with Cushing's disease shortly
      after correction of hypercortisolism.
AB  - In the present study, we characterized the changes in plasma leptin levels in
      patients with pituitary Cushing's disease and in age- and sex-matched controls.
      Plasma levels of ACTH, cortisol, and leptin were measured before and after iv
      administration of ovine CRH in controls once and in patients twice (while they
      had active hypercortisolism and 10 days after successful surgery). Cushing's
      patients had elevated body mass indexes (34 +/- 1.9 vs. 22.9 +/- 0.8) and plasma
      leptin levels (35.6 +/- 3.4 vs. 9.2 +/- 1.9 ng/mL) compared to controls, which
      remained unchanged 10 days after successful transsphenoidal surgery and directly
      proportional to the body mass index. Plasma leptin levels were not affected by
      CRH infusion in either the controls or the patients despite clear-cut elevations
      in plasma ACTH and cortisol. These findings suggest that although acute changes
      in plasma cortisol do not affect plasma leptin, chronic hypercortisolism results
      in elevated leptin levels, probably by causing visceral obesity.

PMID- 9253365
TI  - Nocturnal rise of leptin in normal prepubertal and pubertal children and in
      patients with perinatal stalk-transection syndrome.
AB  - We studied 24-h profiles of circulating leptin levels using a sensitive and
      specific radioimmunoassay in healthy pre- (Tanner 1) and pubertal boys and girls
      (Tanner 3-4) as well as in a group of patients with perinatal stalk-transection
      syndrome. Similar nyctohemeral rhythm in serum leptin levels were found in
      prepubertal (MESOR: 2.34 +/- 0.2 ng/ml; amplitude 0.32 +/- 0.1 ng/ml) and
      pubertal boys (MESOR 2.2 +/- 0.2 ng/ml; amplitude 0.38 +/- 0.07 ng/ml). Likewise,
      no differences were found between prepubertal (MESOR 6.6 +/- 1.07 ng/ml;
      amplitude 1.67 +/- 0.4 ng/ml) and pubertal girls (MESOR 4.05 +/- 0.5 ng/ml;
      amplitude 0.95 +/- 0.2 ng/ml). In contrast, higher MESOR (p < 0.002) and
      amplitude values (p < 0.005) were found in prepubertal and pubertal girls than in
      prepubertal and pubertal boys. Finally a significant nyctohemeral rhythm in serum
      leptin levels was found in patients with perinatal stalk-transection syndrome
      (MESOR: 9.3 +/- 2.3 ng/ml; amplitude 1.46 +/- 0.4 ng/ml). This data shows the
      existence of sexual dimorphism in the nyctohemeral rhythm in serum leptin levels
      that are not influenced by the pubertal stage or by pulsatile anterior pituitary
      hormone secretion.

PMID- 9253366
TI  - Interest of routine measurement of serum calcitonin: study of thyroidectomized
      patients.

PMID- 9253367
TI  - Prolactinomas apparently resistant to quinagolide respond to cabergoline therapy.

PMID- 9253368
TI  - Prolactinomas apparently resistant to quinagolide respond to cabergoline therapy.

PMID- 9253369
TI  - Immunocytochemical localization of gonadotropin and gonadal steroid receptors in
      human pineal glands.

PMID- 9253370
TI  - Some reflections and hypotheses on the pathophysiology of female urinary
      incontinence.
AB  - It is proposed that opening and closure of the proximal urethra and bladder neck
      are regulated by a battery of surrounding structures, the most important being
      the pubourethral-vesical ligaments, the suburethral vaginal wall, 'the hammock',
      the pubococcygeus muscles, the levator plate and the connective tissue which like
      glue connects these structures to each other. Inappropriate function in one of
      these structures can, to some extent, be compensated for by an improved function
      in another hereby maintaining continence. However, a significantly deteriorated
      function in the support of urethra--normally maintained by the
      pubourethral/pubovesical ligaments, the pubococcygeus muscles and suburethral
      vaginal wall--will result in pronounced stress incontinence. Severe defects in
      these structures can generally not be compensated for by exercises of the pelvic
      muscles. This is true, in particular, if there is also a defect function in the
      connective tissue which 'glues' the urogenital structures to each other. Under
      such circumstances surgical procedures have to be considered to alleviate the
      patients symptoms. What is said so far must not exclude the importance of
      recognizing the role of the internal urethral structures to maintain continence,
      in particular the quality of urethral muscles, connective tissue and
      vascularization. In some specific cases of mixed incontinence it can be
      speculated whether the urge symptom can be caused by an anatomical dysfunction
      causing the proximal urethra and the bladder neck to remain involuntarily open or
      to open promptly at even minor pressure provocations. If so distension of the
      bladder neck and proximal urethra may activate stretch receptors located here
      which will induce uninhibited detrusor contractions. The presence of estrogen
      receptors in many of the structures involved in preserving continence may explain
      the increased prevalence of dysfunctions in the urogenital tract in
      postmenopausal patients, in particular in those not on hormone replacement
      therapy.

PMID- 9253371
TI  - Reliability of diagnostic tests.
AB  - The reliability of a diagnostic test depends on the accuracy and reproducibility
      of the test results. The accuracy is defined by comparing the test results with a
      final true diagnosis. The predictive values are here the most important clinical
      measures. Since it may be impossible to establish a final true diagnosis the
      reliability must in some cases be measured by a determination of reproducibility.
      The reproducibility is measured by comparing results of repeated examinations of
      the same patient. The reproducibility is measured by the use of the kappa
      coefficient which adjusts the observed agreement for expected chance agreement. A
      study of reliability of a diagnostic test should fulfill the same methodological
      requirements as other clinical studies. Both the predictive values and the kappa
      coefficient are supposed to depend on the prevalence and this should be noticed
      when results of different studies are compared. Reliability of diagnostic tests
      is often poor and scientific development of how to improve clinicians' diagnostic
      practice is much needed.

PMID- 9253372
TI  - Patient history in the diagnosis of urinary incontinence and determining the
      quality of life.

PMID- 9253373
TI  - The value of clinical examination of the female incontinent patient.
AB  - The role of different instruments in evaluation of disturbance in the lower
      urinary tract has been discussed briefly, emphasizing simplicity and the power of
      the contact between the physician and the patient. A good history based on clear
      and descriptive language is still the milestone in making the correct diagnosis.
      Combined with a proper physical examination and simple inexpensive and time
      saving clinical examination this may leave only few patients requiring
      sophisticated multichannel urodynamic equipment before the adequate treatment can
      be offered. One should bear in mind that the world is facing diminishing medical
      resources at the same time as there are more and more women seeking help for
      their incontinence. Therefore the measurements must be cost effective and patient
      friendly.

PMID- 9253374
TI  - Frequency/volume chart: the basic tool for investigating urinary symptoms.
AB  - BACKGROUND: This article reviews the literature on the frequency/volume chart.
      The frequency/volume chart is the systematic registration of point of time of
      voiding and voided volume done by the patient in her own environment for a
      specified period of time, usually 24 or 48 hours. The chart can be supplemented
      with the registration of incontinence episodes. Measurements obtained from the
      frequency/volume chart include total voided volume/24 hours, frequency of
      micturition, mean voided volume, largest single voided volume and range of voided
      volumes. RESULTS: Normal values for these measurements as well as values for
      patients with stress incontinence and detrusor instability are presented.
      CONCLUSIONS: The frequency/volume chart is a simple and inexpensive way of
      recording basic data, some of which can be obtained in no other way, e.g. total
      voided volume. The frequency/ volume chart has acceptable reproducibility but
      limited diagnostic capacity. It provides a basis for instituting treatment in
      many patients and provides the best tool for following the result of treatment in
      patients with the urge syndrome.

PMID- 9253375
TI  - Pad weighing tests: the best way to quantify urine loss in patients with
      incontinence.
AB  - This article reviews the literature on pad weighing tests composed to measure
      urinary incontinence. The tests can be divided into short-term tests (one to two
      hours) performed in a clinic or laboratory, or long-term tests (12 to 48 hours)
      performed by the patient at home. The short-term tests, apart from practical
      disadvantages, have low negative predictive value and require retrograde filling
      of the bladder to reach acceptable reproducibility. The long-term tests have
      practical advantages, better sensitivity and acceptable reproducibility. Pad
      weighing tests have no value for the purpose of differential diagnosis. The
      validity of the long-term test as a measure of the symptom of urinary
      incontinence is obvious whereas it is unclear what the short-term test measures.

PMID- 9253376
TI  - Reliability and validity of stationary cystometry, stationary cysto-urethrometry
      and ambulatory cysto-urethro-vaginometry.
AB  - OBJECTIVE: The purpose of this article is to evaluate the reliability and
      validity of stationary cystometry, stationary cysto-urethrometry and ambulatory
      cysto-urethro-vaginometry for the diagnosis of urinary incontinence. MATERIAL AND
      METHODS: Literature search on reproducibility of cystometry is based on articles
      written in the English language found in Medline from 1987 to 1993. Five articles
      were found. These articles had references for another 6 older articles about the
      same topic. One recently published article is evaluated as well. Data about
      reproducibility of cystometry performed in these studies are given. Knowledge of
      reproducibility of cystometry combined with urethrometry, urethro-vagino or
      rectometry with leak detection during stationary or ambulatory recording is
      given. An evaluation of validity of the different methods is presented. RESULTS
      AND CONCLUSION: Conflicting data has been found for sensory parameters of
      stationary cystometry such as volume or pressure at first desire to void, strong
      desire to void and maximum cystometric capacity. No data were found concerning
      the reliability of cystometry for the recording of urinary incontinence. The main
      problem of urge-incontinent patients is leakage with a strong feeling of urgency.
      The recording of sensory parameters by cystometry is not valid when the main
      problem is urge incontinence. Cystometry will be valid for the diagnosis of urge
      incontinence when a leak detector is used or a mark is made at the tracings when
      leakage is observed. The reliability of cystometry concerning urge incontinence
      should be documented. The reliability of a urethral pressure recording when the
      urethral catheter is extracorporally fixed is low. The reliability and validity
      of ambulatory cysto-urethro-vaginometry in diagnosing urge incontinence, unstable
      urethra and genuine stress incontinence seems to be good, but needs better
      documentation.

PMID- 9253377
TI  - Urethral pressure measurement.
AB  - BACKGROUND: Urethral pressure measurement is a procedure used for assessment of
      the urethral sphincter function during storage. METHODS: The techniques available
      are subject to significant pitfalls, interpretation problems and test-retest
      variation. CONCLUSION: Urethral pressure profile (UPP) parameters are of limited
      value in the assessment of the urethral sphincter function. The parameters do not
      1) discriminate stress incontinence from other disorders, 2) provide a measure of
      the severity of the condition and 3) return to normal after successful
      incontinence surgery. Urethral pressure profile may be useful in disclosing local
      pathology, in assessment of changes with intervention in the individual patient
      and in selecting patients with 'low pressure urethra' which may have therapeutic
      implications. The quality of our techniques of measurement and our concepts of
      interpretation need to be improved.

PMID- 9253378
TI  - Uroflowmetry and pressure/flow study of voiding in women.
AB  - BACKGROUND: Uroflowmetry and pressure-flow study are procedures used for the
      evaluation of micturition. METHODS: Uroflowmetry is mainly a screening test to
      pick up abnormal voiding patterns and an abnormal trace warrants further
      investigation. A certain test-retest variation exists in terms of flow-rates and
      pattern. CONCLUSION: Uroflowmetry is not helpful in diagnosing the types of
      incontinence found in women and its value as a routine test in the assessment of
      incontinent patients remains to be documented. Pressure-flow study of voiding
      enables the differentiation between true obstruction and of a hypoactive detrusor
      function. Test-retest variation of the obtained parameters, however, is
      significant. The role of pressure-flow study voiding in the preoperative
      assessment of patients with stress incontinence needs clarification.

PMID- 9253379
TI  - Techniques for imaging bladder support.
AB  - BACKGROUND: Imaging techniques of bladder support can be of diagnostic value to
      differ causes of urinary incontinence like misbuilding of the lower urinary
      tract, hypermobility of the bladderneck and urethral wall pathology, which is
      valuable prior to surgery for incontinence. METHOD: Literature about imaging
      techniques, especially, voiding cystourethrography, ultrasonography and MRI were
      studied and their diagnostic value evaluated. CONCLUSION: Dynamic ultrasonography
      is the first line imaging method for studying bladder support. Bladderneck
      hypermobility, as a sign of defect in the adjunctive closure forces is better
      correlated to stress incontinence than bladder morfology, diagnosed during static
      cystography. Voiding cystography has its place in diagnosing misbuildings of the
      lower urinary tract. MRI is just at the beginning of its clinical era, and seems
      relevant for studies of urethral pathology.

PMID- 9253380
TI  - Clinical neurophysiological methods for investigating the lower urinary tract in
      patients with micturition disorders.
AB  - METHODS: Different clinical neurophysiological methods used in the investigation
      of patients with micturition disorders are summarized in a short critical review.
      The techniques of measuring nerve conduction velocities, sacral reflex latencies,
      cortical evoked potentials, sensory thresholds, concentric needle EMG and single
      fibre EMG are described and the clinical applications of the different methods
      are reported. CONCLUSION: It is concluded that the neurophysiological tests are
      mainly useful in establishing the integrity of the peripheral innervation of the
      pelvic floor and in case of neurogenic lesions, the combination of different
      methods might show the level of the lesion.

PMID- 9253381
TI  - Consensus of basic assessment of female incontinence.

PMID- 9253382
TI  - Evolution of transcription-regulating proteins: caveat lector!
AB  - The paper of Hawkins et al. [Gene 146 (1994) 145-158] reports incorrect
      descriptions of mutant phenotypes, omits mention of the absence of a highly
      relevant glutamine-binding site and contains sequence alignments which might
      mislead the reader. Extensive sequence analysis reveals as untenable a central
      hypothesis of the paper concerning a possible evolutionary relationship between
      anthranilate synthetases and the transcription factors mediating nitrogen
      metabolite repression in fungi.

PMID- 9253383
TI  - On wisdom after the event.

PMID- 9253384
TI  - On reaching the tunnel at the end of the light.

PMID- 9253385
TI  - Measurement of morning stiffness in rheumatoid arthritis clinical trials.
AB  - OBJECTIVE: Morning stiffness (MS) is a common problem for patients with
      rheumatoid arthritis (RA). However the clinical evaluation of the symptom has
      proved to be difficult. The aim of the study was to determine the responsiveness
      of two methods for measuring MS. METHODS: Data from an uncontrolled (n = 63) and
      a controlled study (n = 80) of inpatient multidisciplinary team care for RA were
      analyzed. MS was measured by its duration to maximum improvement and by its
      severity on a visual analog scale (VAS). The responsiveness of both assessment
      methods was computed by calculating effect sizes and t-statistics, and by
      receiver operating characteristic (ROC) curves with clinical improvement
      according to the definition of the American College of Rheumatology as an
      external criterion. RESULTS: With respect to the ability to detect a clinical
      improvement between admission and discharge in the uncontrolled study, and a
      difference in improvement between the treatment and the control group in the
      controlled study, the effect sizes and t-values of the VAS for severity of MS
      were consistently higher than those of the duration of MS. In contrast to the
      duration, the responsiveness of the VAS for MS compared favorably with the
      responsiveness of other endpoint measures. The ROC surface area of the VAS was
      higher than that of the duration. CONCLUSION: For the evaluation of MS in RA
      clinical trials, the assessment of MS by a severity score is more responsive than
      one based on duration and compares favorably with the performance of other
      endpoint measures.

PMID- 9253386
TI  - The role of change in physical performance in determining risk for dependence in
      activities of daily living among nondisabled community-living elderly persons.
AB  - Among community-living elderly persons, a single assessment of physical
      performance is a powerful predictor of dependence in activities of daily living
      (ADLs). The aim of this study was to determine whether an assessment of change in
      physical performance provides useful prognostic information beyond that available
      from a single assessment. Among a large representative cohort of elderly persons,
      we evaluated the 586 participants who were ADL independent at both the baseline
      and the one year interviews. For each of the three timed tests, participants who
      had a large decline in physical performance were significantly more likely to
      develop ADL dependence at three years than those who improved or showed no
      change. After adjusting for 1-year scores, however, change in physical
      performance was no longer associated with ADL dependence. However, among the 775
      participants who were ADL independent at the baseline interview, change in
      physical performance was significantly associated with the onset of ADL
      dependence at one year, even after adjusting for baseline performance. When
      determining risk for ADL dependence, an assessment of change in physical
      performance over one year does not provide useful prognostic information beyond
      that available from a single assessment. Nevertheless, change in physical
      performance is independently associated with concurrent ADL dependence and may be
      useful in predicting future disability if measured over shorter intervals.

PMID- 9253387
TI  - Comparison of two procedures to estimate the hospital stay attributable to
      nosocomial infection: matched cohort study versus analysis of covariance of the
      total unmatched cohort.
AB  - We compare the results of a matched cohort study with those yielded by analysis
      of covariance (ANCOVA) in the cohort where the matched study was nested to assess
      whether the matching design underestimates (as it has been assumed) the extra
      length of hospitalization due to nosocomial infection. A total of 218 patients
      developed hospital infection in a cohort of 1483 general surgery patients; 161
      were successfully matched 1:1 for surgical procedure, ASA score, age (+/-10
      years), emergency-scheduled surgery, preoperative stay, and, whenever possible,
      number of diagnoses and sex. Unmatched infected patients (57, 23.1%) were
      different from matched ones. There were no differences for the variables between
      matched infected patients and their pairs. The matched cohort study overestimates
      the extra LOH due to hospital infection. The use of ANCOVA in the total cohort
      obviates the selection bias of the matched cohort design.

PMID- 9253388
TI  - Cardiovascular morbidity and mortality among hypertensive patients in general
      practice: the evaluation of long-term systematic management.
AB  - OBJECTIVE: To evaluate systematic management of hypertensive patients with regard
      to cardiovascular morbidity and mortality. DESIGN: In a matched cohort study
      (1978-1993) the number of cardiovascular events among hypertensive patients under
      continuous systematic management in four general practices was compared with
      those occurring among hypertensive patients from eight "usual care" general
      practices. SUBJECTS: The source population consisted of employees of a major
      electronic company in Eindhoven with hypertension as determined at an
      occupational health examination. The index group (n = 120) consisted of employees
      who were participating in the systematic management program in four practices. A
      reference group of 120 patients was selected from hypertensive employees who were
      registered in eight "usual care" practices by matching for age, gender, fasting
      blood glucose, and frequency of occupational health examinations. The total
      cohort consisted primarily of males (78%), whose ages ranged from 50 to 65 years.
      MAIN OUTCOME MEASURES: Risk difference (RD) per 1000 patient years regarding left
      ventricular hypertrophy, heart failure, angina pectoris, myocardial infarction,
      transient ischaemic attack, stroke, peripheral arterial disease, nephropathy,
      retinopathy, cardiac death, death due to stroke, and non-cardiovascular death was
      determined. In addition to morbidity and mortality, systematic hypertension
      management was evaluated with regard to cardiovascular risk factors throughout a
      period of maximally 12 successive years (1978-1989). Morbidity and mortality data
      were derived from general practice records and archives; data on risk factors
      were assessed at bi-annual occupational health examinations. RESULTS: The total
      follow-up duration amounted to 2628 patient years. The mean follow-up duration in
      the index group was 10.8, in the reference group 11.1 years. As compared to the
      "usual care" reference group, the index group showed less left ventricular
      hypertrophy (RD 8.2, 95% CI 1.4-15.0), less angina pectoris (RD 9.7, 95% CI 2.0
      17.4) and less peripheral arterial disease (RD 3.7, 95% CI 0.5-7.1). The
      difference in mean decrease in blood pressure during follow-up was 11.3 mmHg
      systolic and 5.9 mmHg diastolic in favour of the index group. No significant
      differences between the index and the reference groups were found with regard to
      the changes in other risk factors. CONCLUSION: In our study systematic management
      of hypertensive patients aged 50 to 65 in general practice was associated with a
      statistically significant, and clinically relevant decrease in cardiovascular
      morbidity and blood pressure. Although causality cannot be determined from this
      non-randomized cohort study, the findings do support the view that systematic
      management of hypertensive patients in general practice is valuable.

PMID- 9253389
TI  - Decreasing mortality from acute myocardial infarctions: effect of attack rates
      and case severity.
AB  - Mortality from myocardial infarction (MI) has declined in many countries and the
      reasons for the decline have not been fully quantified. We used the database of
      the Halifax County MONICA Project to test the hypothesis that the decline of in
      hospital mortality from MI can be explained by a trend toward less severe disease
      as opposed to improved treatment. During the study period 1984-1993, 14,130
      people aged 25-74 had been admitted to hospital with suspected MI. Of these, 3774
      were diagnosed as definite MI by standardized criteria (480 fatal). For each
      patient, clinical history, serial cardiac enzymes, and ECG treatment regimen
      during hospital stay were extracted from patient charts. Survival status 28 days
      after onset of symptoms was determined. A severity index predicting 28-day case
      fatality was derived from health status at admission time. During the study
      period the rate of definite MI in the MONICA target population showed a general
      downward trend from 221 to 179 per 100,000/year (p = 0.0002). The severity index
      increased during the observation time (p < 0.0001), predicting 25% higher
      mortality. Case fatality fluctuated, but showed a marginally significant decline.
      We conclude that part of the decreased in-hospital mortality from MI is due to
      lower attack rates. The remainder occurred despite increased case severity and is
      possibly due to improved in-hospital treatment.

PMID- 9253390
TI  - Efficiency optimization of the selection period in therapeutic trials.
AB  - To determine eligibility for a (randomized) clinical trial, measuring the
      inclusion and exclusion criteria can be extended over a period of time. During
      this period, known as the selection period, a patient is repeatedly examined at
      certain time intervals. This study describes an approach for optimizing the
      efficiency of the selection period. Efficiency is defined as the costs of
      randomizing one patient. The objective is to construct prediction models based on
      data obtained early in the selection period to predict subsequent exclusions. A
      prediction model increases the efficiency if after its application the costs per
      randomization are lower. The approach is illustrated using data from the
      selection period of the Rotterdam Cardiovascular Risk Intervention (ROCARI) trial
      which was composed of five consecutive patient visits. At each visit, data to
      determine eligibility was obtained. We found that logistic regression models
      based on data of the first and second visit could predict exclusions during the
      third visit. Application of the prediction models suggested that in this
      particular trial the costs per randomization would decrease by $52. As the
      initial costs per randomization were $1444, there would be a 3.6% (52/1444)
      savings in recruitment costs under the prediction models, accounting for a
      savings of more than $450,000. We conclude that the use of data obtained early in
      a selection period can predict subsequent exclusions, and therefore could
      increase the efficiency of such a period. The approach could be applied to data
      obtained in a pilot study as well as data obtained in the beginning of a
      prolonged intake period.

PMID- 9253391
TI  - Left, right, near or far wall common carotid intima-media thickness measurements:
      associations with cardiovascular disease and lower extremity arterial
      atherosclerosis.
AB  - We evaluated the differences in strength of the associations of prevalent
      cardiovascular disease and lower extremity arterial atherosclerosis to common
      carotid intima-media thickness, assessed by near wall measurements only, by far
      wall measurements only, and by the average of near and far wall measurements. The
      study was based on data from 1500 participants of the Rotterdam Study, a single
      center-population-based prospective follow-up study among 7983 subjects, aged 55
      years or over. Comparison of the strength of the associations of near wall intima
      media thickness and of combined near and far wall intima-media thickness to
      cardiovascular disease and lower extremity arterial atherosclerosis revealed
      significantly stronger associations compared to associations observed for far
      wall intima-media thickness, in particular for stroke and lower extremity
      arterial disease. We conclude that near wall common carotid intima-media
      thickness measurement provides at least as good an indicator of atherosclerosis
      elsewhere and of cardiovascular risk as the far wall intima-media thickness
      measurement.

PMID- 9253392
TI  - Interaction fallacy.
AB  - We define interaction fallacy as the situation in which heterogeneity of odds
      ratios suggests an interaction that does actually not exist among the
      corresponding risk ratios. We provide a hypothetical example of interaction
      fallacy between the presence of the germ-line BRCA1 mutation, age at first live
      birth, and breast cancer risk based on data from the literature. More generally,
      we present a set of hypothetical conditions under which interaction fallacy may
      occur.

PMID- 9253393
TI  - Cost-benefit analyses in the health-care literature: don't judge a study by its
      label.
AB  - OBJECTIVES: To assess whether health-care related economic evaluations labeled as
      "cost benefit analyses" (CBA) meet a contemporary definition of CBA methodology
      and to assess the prevalence of methods used for assigning monetary units to
      health outcomes. DATA SOURCES: Medline, Current Contents, and HSTAR databases and
      reference lists of review articles, 1991-1995. STUDY SELECTION: Economic analyses
      labeled as CBAs were included. Agreement on study selection was assessed. STUDY
      EVALUATION: CBA studies were classified according to standard definitions of
      economic analytical techniques. For those valuing health outcomes in monetary
      units (bona fide CBAs), the method of valuation was classified. RESULTS: 53% of
      95 studies were reclassified as cost comparisons because health outcomes were not
      appraised. Among the 32% considered bona fide CBAs, the human capital approach
      was employed to value health states in monetary units in 70%. Contingent
      valuation methods were employed infrequently (13%). CONCLUSIONS: Studies labeled
      as CBAs in the health-care literature often offer only partial program
      evaluation. Decisions based only on resource costs are unlikely to improve
      efficiency in resource allocation. Among bona fide CBAs, the human capital
      approach was most commonly used to valuing health, despite its limitations. The
      results of health-care related CBAs should be interpreted with extreme caution.

PMID- 9253394
TI  - Assessing non-consent bias with parallel randomized and nonrandomized clinical
      trials.
AB  - In some randomized clinical trials, a large proportion of patients eligible for
      randomization may withhold consent to be randomized. When the subjects in the
      randomized trial differ from the eligible population with respect to
      characteristics that are associated with the magnitude of the treatment effect,
      there may be non-consent bias, i.e., the treatment effect for those in the
      randomized trial may not reflect the treatment effect for the eligible
      population. In response to this problem, some investigators have conducted, in
      addition to the randomized trial, a separate nonrandomized but otherwise
      identical trial consisting of those patients who are eligible for randomization,
      but instead choose their own treatment. Observed baseline covariate data can be
      used to adjust for differences between the randomized population and the eligible
      population when estimating the treatment effect for the eligible population.
      After adjusting, different outcomes for the randomized versus nonrandomized
      treated groups and/or the randomized versus nonrandomized control groups reflect
      the presence of hidden non-consent bias resulting from differences between the
      trial population and the eligible population with respect to unobserved
      covariates. A sensitivity analysis can display how hidden non-consent bias can
      account for an imbalance in the treatment groups with respect to an unobserved
      covariate. A parallel randomized and nonrandomized trial which compares
      adenoidectomy versus medical treatment for children with recurrent otitis media
      [Paradise et al. Efficacy of adenoidectomy for recurrent otitis media in children
      previously treated with tympanostomy-tube placement. J Am Med Assoc 1990; 263:
      2066-2073] is used as an illustration.

PMID- 9253395
TI  - Reliability and validity of self-report CD4 counts-in persons hospitalized with
      HIV disease.
AB  - Studies of health care outcomes and clinical decision making for people with HIV
      disease depend on CD4 cell count data to accurately assess the stage of disease.
      The possibility of obtaining reliable and valid data from self-reported CD4
      counts is an unexplored source of potentially important, cost-effective
      information for these purposes. We examined the extent of agreement of self
      reported CD4 counts with medical record CD4 among 120 patients (95% male, 69%
      white, 5% injection drug users) hospitalized with HIV-related illness at seven
      Los Angeles area hospitals. Average record and report CD4 counts did not differ
      significantly, and record and report CD4 counts were highly correlated (product
      moment correlation of 0.84, intraclass correlation of 0.82). Agreement between
      self-reports and medical records varied by CD4 level: at higher levels of CD4,
      the differences between self-reports and medical records tended to be larger,
      with self-reports yielding upwardly biased estimates compared to the medical
      records. These findings suggest that self-report CD4 data may provide clinically
      adequate estimates of true CD4 counts. The study needs to be replicated in other
      populations, notably those with larger numbers of subjects who are female, of
      minority ethnicity, or injection drug users.

PMID- 9253396
TI  - Body mass index compared to dual-energy x-ray absorptiometry: evidence for a
      spectrum bias.
AB  - The objective of this study was to evaluate the accuracy of body mass index (BMI)
      in the diagnosis of obesity. The relationship of this weight-for-height index to
      body composition was determined using dual-energy x-ray absorptiometry (DEXA) in
      226 Caucasian subjects. BMI-obesity was defined as a BMI greater than 27.8 kg/m2
      in males and greater than 27.3 kg/m2 in females. BMI-obesity was weakly sensitive
      (males: 12.5%, females 13.6%) compared with diagnosis by DEXA, defined as percent
      body fat mass (%BF) greater than 20% in males and greater than 25% in females.
      Conversely, the specificity of BMI-obesity was high (males and females: 100%).
      When analyzing subgroups of subjects according to weight, sensitivity was higher
      among heavier subjects than among lighter ones. In both sexes and in all
      subgroups, the specificity was 100%. The clinical implication of this spectrum
      bias is that, in men or women weighing less than 80 kg, measures of obesity other
      than BMI, such as bioelectrical impedance, should be preferred.

PMID- 9253397
TI  - Epidemiological evidence for the disruption of ionized calcium homeostasis in the
      elderly.
AB  - Ionized calcium (Ca2+), phosphate, albumin, total calcium, and pH measurements
      taken from participants in a large population-based epidemiological study were
      examined to determine the change in physiological variation with age for persons
      over 43 years old. Only Ca2+ showed a statistically significant increase in SD
      with age (p < 0.0001). The Ca2+ coefficients of variation (CV) increased from
      2.92% in the youngest age group (43-54 years) to 3.69% in the oldest age group
      (75-86 years of age). In females, the increase in Ca2+ variability was nearly
      complete by age 55. Males also showed a significant (p = 0.006) increase in SD
      between the 43-54 age group and the 55-64 age group, however, Ca2+ variability
      did not plateau after age 55 in men as it did in women. In the 43-54 (p = 0.04)
      and 55-64 (p = 0.03) age group men showed significantly better physiological
      control of Ca2+ than women. Phosphate showed a slight decrease in CV with age.
      These data suggest that Ca2+ homeostasis is disrupted in the same age groups that
      are most vulnerable to osteoporosis.

PMID- 9253398
TI  - The association between nulliparity and gestational hypertension.
AB  - The association between nulliparity and gestational hypertension was examined by
      analysis of the 1988 National Maternal and Infant Health Survey. Gestational
      hypertension was defined as the occurrence of two consecutive diastolic blood
      pressure readings > or = 90 mm Hg after 20 completed weeks gestation in the
      absence of proteinuria in subjects normotensive prior to pregnancy. Preeclampsia
      was defined as gestational hypertension in the presence of significant
      proteinuria. Using logistic regression, 110 subjects with gestational
      hypertension and 34 subjects with preeclampsia were compared with 4371 subjects
      free of all hypertensive disorders. Nulliparity was weakly associated with an
      increase in the risk of gestational hypertension among whites (odds ratio, 95%
      confidence interval: 1.58 [0.92-2.74]) and not associated with risk among blacks
      (1.09 [0.51-2.35]). Preeclampsia was strongly associated with increased risk
      among whites (2.86 [0.94-8.73]) and blacks (2.94 [0.94-9.18]). The small increase
      in risk of gestational hypertension associated with nulliparity in contrast with
      the large increase in risk of preeclampsia suggests that these disorders may have
      a different etiology.

PMID- 9253399
TI  - Potential adverse outcomes of psychotropic and narcotic drug use in Canadian
      seniors.
AB  - Potential adverse outcomes (falls, impaired cognition, impaired self-care) of
      psychotropic (benzodiazepines, antidepressants, antipsychotics) and narcotic
      medication use were examined in a large sample of Canadians 65 years of age and
      older. We examined rates of reported falls, Digit Symbol Substitution Test (DSST)
      scores, and mean number of self-care impairments for those consuming psychotropic
      and/or narcotic drugs as compared to non-users. Use of psychotropic drugs and/or
      narcotics was associated with an increased prevalence of falls, lower DSST
      scores, and/or number of self-care difficulties. For example, in subjects who
      were cognitively normal, the frequency of falls was 60% greater in benzodiazepine
      users and 120% greater in users of antidepressants as compared to non-users.
      Adverse outcomes increased with the number of classes of psychotropic or narcotic
      medications used. These effects were most pronounced in cognitively normal
      subjects where the prevalence of falls increased from 13.9% in those consuming
      none of the medication classes to 42.6% for users of two or more classes. In
      subjects with mild dementia the use of these medications was not associated with
      any significant differences in the outcomes measured. Regression models showed
      that benzodiazepine, antidepressant, and narcotic use remained significant
      explanatory variables for potential adverse outcomes even after simultaneously
      considering the effects of several other variables. Although further work is
      necessary, our results suggest that individuals with better cognitive function
      may be at particular risk for adverse effects with use of these medications.

PMID- 9253400
TI  - Albumin as a predictor of mortality in elderly patients.

PMID- 9253401
TI  - Red, cold and dead?

PMID- 9253402
TI  - AZT monophosphate knocks thymidylate kinase for a loop.

PMID- 9253403
TI  - RNA aptamers.

PMID- 9253404
TI  - Structure of thymidylate kinase reveals the cause behind the limiting step in AZT
      activation.

PMID- 9253405
TI  - Domain packing and dynamics in the DNA complex of the N-terminal zinc fingers of
      TFIIIA.
AB  - The three N-terminal zinc fingers of transcription factor IIIA bind in the DNA
      major groove. Substantial packing interfaces are formed between adjacent fingers,
      the linkers lose their intrinsic flexibility upon DNA binding, and several lysine
      side chains implicated in DNA recognition are dynamically disordered.

PMID- 9253406
TI  - Three-dimensional structure of the Ras-interacting domain of RalGDS.
AB  - The Ras-interacting domains of the the protein-kinase Raf and the Ral guanine
      nucleotide dissociation stimulator, RalGDS, lack extensive sequence similarity,
      but their overall three-dimensional structures are very similar to each other.
      Mutational analysis indicated that three residues in the RalGDS domain are
      critical for its interaction with Ras.

PMID- 9253407
TI  - Crystal structure of a trapped phosphoenzyme during a catalytic reaction.
AB  - The crystal structure of the fructose-2,6-bisphosphatase domain trapped during
      the reaction reveal a phosphorylated His 258, and a water molecule immobilized by
      the product, fructose-6-phosphate. The geometry suggests that the
      dephosphorylation step requires prior removal of the product for an 'associative
      in-line' phosphoryl transfer to the catalytic water.

PMID- 9253408
TI  - Trapping and visualization of a covalent enzyme-phosphate intermediate.
AB  - Using a mutant version of E. coli alkaline phosphatase, we succeeded in trapping
      and determining the structure of the phospho-enzyme intermediate. The X-ray
      structure also revealed the catalytic water molecule, bound to one of the active
      site zinc ions, positioned ideally for the apical attack necessary for the
      hydrolysis of the intermediate.

PMID- 9253409
TI  - Crystal structure at 2.8 A resolution of anabolic ornithine transcarbamylase from
      Escherichia coli.

PMID- 9253410
TI  - Protein structural classes in five complete genomes.
AB  - The predicted distribution of globular proteins over folding types in five
      complete genomes differs from the tendencies observed in known protein
      structures. The ratio between the number of predicted membrane and globular
      proteins is conserved.

PMID- 9253411
TI  - Picture story. Trimers and tumours.

PMID- 9253412
TI  - A residue-specific NMR view of the non-cooperative unfolding of a molten globule.
AB  - Molten globules are partially folded forms of proteins that are thought to be
      general intermediates in protein folding. Nonetheless, there is limited
      structural information about such species because they possess conformational
      heterogeneity and complex dynamical properties that lead to extreme line
      broadening in NMR spectra. Here we use a 2-D NMR approach that overcomes this
      difficulty by detecting the unfolding of individual residues in a molten globule
      in increasing concentrations of denaturant. The results show that the structure
      in the low pH form of alpha-lactalbumin (alpha-LA) is not formed cooperatively.
      Moreover, a core region remains collapsed under extremely denaturing conditions,
      even when the majority of the polypeptide chain is completely unfolded. Our
      results support a model for protein folding in which the core provides a template
      for correct assembly of the remainder of the structure.

PMID- 9253413
TI  - Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc
      binding suggest a novel mode of interaction with MHC class II molecules.
AB  - Bacterial superantigens are small proteins that have a very potent stimulatory
      effect on T lymphocytes through their ability to bind to both MHC class II
      molecules and T-cell receptors. We have determined the three-dimensional
      structure of a Streptococcal superantigen, SPE-C, at 2.4 A resolution. The
      structure shows that SPE-C has the usual superantigen fold, but that the surface
      that forms a generic, low-affinity MHC-binding site in other superantigens is
      here used to create a SPE-C dimer. Instead, MHC class II binding occurs through a
      zinc binding site that is analogous to a similar site in staphylococcal
      enterotoxin A. Consideration of the SPE-C dimer suggests a novel mechanism for
      promotion of MHC aggregation and T-cell activation.

PMID- 9253414
TI  - Interlocking structural motifs mediate molecular discrimination by a theophylline
      binding RNA.
AB  - To visualize the interplay of RNA structural interactions in a ligand binding
      site, we have determined the solution structure of a high affinity RNA
      theophylline complex using NMR spectroscopy. The structure provides insight into
      the ability of this in vitro selected RNA to discriminate theophylline from the
      structurally similar molecule caffeine. Numerous RNA structural motifs combine to
      form a well-ordered binding pocket where an intricate network of hydrogen bonds
      and stacking interactions lock the theophylline into the complex. Two internal
      loops interact to form the binding site which consists of a sandwich of three
      base triples. The complex also contains novel base-zipper and 1-3-2 stacking
      motifs, in addition to an adenosine platform and a reversed sugar. An important
      feature of the RNA is that many of the conserved core residues participate in
      multiple overlapping tertiary interactions. This complex illustrates how
      interlocking structural motifs can be assembled into a highly specific ligand
      binding site that possesses high levels of affinity and molecular discrimination.

PMID- 9253415
TI  - Crystal structure of the EF-Tu.EF-Ts complex from Thermus thermophilus.
AB  - In order to study nucleotide exchange mechanisms in GTP-binding proteins, we have
      determined the crystal structure of the complex formed by the elongation factor
      Tu (EF-Tu) and its exchange factor Ts (EF-Ts) from Thermus thermophilus. The
      complex is a dyad symmetrical heterotetramer in which each EF-Tu, through a
      bipartite interface, interacts with two subunits of EF-Ts, explaining the need
      for a dimeric exchange factor. The architecture of the assembly is distinctly
      different from that of the corresponding heterodimeric E. coli complex, in which
      the monomeric E. coli EF-Ts remarkably forms essentially the same bipartite
      interface with EF-Tu through a sequence/structural repeat. GDP is released
      primarily by a Ts-induced peptide flip in the nucleotide binding pocket that
      disrupts hydrogen bonds to the phosphates and repositions the peptide carbonyl so
      as to sterically and electrostatically eject the GDP. The exchange mechanism may
      have useful implications for receptor-induced exchange in heterotrimeric G
      proteins.

PMID- 9253417
TI  - Structural studies of poliovirus mutants that overcome receptor defects.
AB  - In order to better understand the process of cell entry for non-enveloped
      viruses, we have solved the crystal structures of five poliovirus mutants which
      can infect cells expressing mutant poliovirus receptors. Four of these structures
      have been solved from frozen crystals using cryocrystallographic data collection
      methods. The mutations have a range of structural consequences, from small local
      perturbations to significant loop rearrangements. All of the mutant viruses are
      more labile to conversion to an apparent cell entry intermediate, suggesting that
      these mutant viruses could compensate for the suboptimal receptors by lowering
      the thermal energy required to undergo the receptor-mediated conformational
      change.

PMID- 9253416
TI  - The solution structure of an HMG-I(Y)-DNA complex defines a new architectural
      minor groove binding motif.
AB  - The solution structure of a complex between a truncated form of HMG-I(Y),
      consisting of the second and third DNA binding domains (residues 51-90), and a
      DNA dodecamer containing the PRDII site of the interferon-beta promoter has been
      solved by multidimensional nuclear magnetic resonance spectroscopy. The
      stoichiometry of the complex is one molecule of HMG-I(Y) to two molecules of DNA.
      The structure reveals a new architectural minor groove binding motif which
      stabilizes B-DNA, thereby facilitating the binding of other transcription factors
      in the opposing major groove. The interactions involve a central Arg-Gly-Arg
      motif together with two other modules that participate in extensive hydrophobic
      and polar contracts. The absence of one of these modules in the third DNA binding
      domain accounts for its-100 fold reduced affinity relative to the second one.

PMID- 9253418
TI  - The annual meeting of the European Academy of Allergology and Clinical Immunology
      (EAACI) '97. Rhodes, Hellas, June 1-5, 1997. Abstracts.

PMID- 9253419
TI  - 12th Annual meeting of the American Society of Primatologists. San Diego,
      California, June 27-July 1997. Abstracts.

PMID- 9253420
TI  - [XVII Brazilian Congress of Neurology. 16 September 1996. Abstracts].

PMID- 9253421
TI  - [III Sao Paulo Congress of Neurology and Child Psychiatry. 28-30 November 1996.
      Abstracts].

PMID- 9253423
TI  - Cumulative index volumes 16 through 25.

PMID- 9253422
TI  - [Dermatology--guidelines and quality assurance for diagnosis and therapy. 39th
      Session of the German Dermatologic Society, Association of German-language
      Dermatologists. Karlsruhe, 23-26 April 1997. Abstracts].

PMID- 9253424
TI  - 7th Interscience World Conference on Inflammation, Antirheumatics, Analgesics,
      Immunomodulators. Geneva, Switzerland, 19-21 May 1997. Abstracts.

PMID- 9253425
TI  - [90th Annual meeting of the Swiss Society of Pediatrics. Geneva, 19-21 June 1997.
      Abstract].

PMID- 9253426
TI  - [63rd Annual meeting of the German Society of Cardiology and Cardiovascular
      Research. Mannheim, 3-5 April 1997. Abstracts].

PMID- 9253427
TI  - [German Society of Neurosurgery 48th annual meeting. Berlin, 27-30 April 1997.
      Abstract].

PMID- 9253428
TI  - Matching program for appointment to residency training in neurological surgery in
      United States.

PMID- 9253429
TI  - National mechanisms for the selection of trainees. Procedure in Great Britain.

PMID- 9253430
TI  - Leadership qualities in prominent neurosurgeons.
AB  - Our questionnaire provided a unique occasion to unravel the characteristics of
      leading neurosurgeons. As is also the case for successful leaders in other
      fields, neurosurgical leaders are good at school, used to being confronted with
      dilemmas, truthloving, ambitious, and, of course, gifted. They constitute a
      hardworking elite. The key to success is awareness. Awareness of oneself
      awareness of one's surroundings, awareness of the message to be delivered,
      awareness of the difficulties to be overcome and of their solutions. Awareness
      requires mental readiness, and this is directly linked to performance excellence
      in surgery [6].

PMID- 9253431
TI  - Criteria to find qualified candidates--professional personnel recruitment methods
      adapted to neurosurgery.
AB  - A neurosurgeon has not received any special training in personnel recruitment at
      the time he becomes chief of a department. Consequently, a suboptimal personnel
      policy is most probable. Due to the rapid changes in social behaviour and style
      of leadership in postwar Europe, he might be ill advised to follow only the
      example of his successful predecessors, apart from the fact, that this would only
      be possible if the personalities (of the former and new chief) were similar. To
      save time and energy for optimal patient care, personnel recruitment can be
      improved and made more reproducible and reliable by adopting modern, professional
      non-medical principles. A typical stepwise process of personnel recruitment
      includes an analysis of the position and function, the definition of demands and
      offers, the choice of advertising and searching methods, the analysis of the
      application documents, the interview with the candidate including its re
      evaluation and the ongoing evaluation process during the training. This election
      process is not only conducted by the chief of a department, but also by senior
      staff-members and even young, competing assistants. It aims to find the candidate
      who fits best in the requirements, who will be trained and educated with the
      least effort and who has the best potential to succeed in the long run. The only
      factors seemingly predicting a good development of a candidate are personality,
      energy (potential, motivation) and intelligence. Therefore, the search should
      especially aim to discover these-admittedly difficult to detect-qualities.

PMID- 9253432
TI  - Criteria and procedures in the automotive industry.

PMID- 9253433
TI  - Selection of Air Force officers--profiles, criteria, testing.
AB  - The article presents an explanation of the selection process for German Air Force
      (GAF) officers in general, and those for flying duty in particular. The text
      includes an overview of the entire selection and training process, the desired
      profiles and characteristics of GAF officers, criteria for evaluating current
      officers, and statistics which show the results of this process.

PMID- 9253434
TI  - Can we define or measure manual skills in surgical training?
AB  - Neurosurgery requires manual dexterity. But should tests be devised to assess
      manual skills as part of a selection process for training or used as a means of
      determining surgical competence? The paper debates this fundamental question and
      proposes that manual skills for neurosurgical tasks need to be defined within the
      overall context of a recognised and fully assessed training programme. The
      importance of training as a means of transferring competence, part of which is
      manual skills, is emphasised. In conclusion the paper points out the inadequacy
      of solely measuring manual skills, were it possible, in assessing neurosurgical
      competence.

PMID- 9253435
TI  - How many residents should we train? The USA experience.
AB  - Over the past ten years, an average of 135 residents have entered neurosurgical
      training in the United States each year. These neurosurgeons-to-be come from
      about 250 applicants who annually enter the national matching program for
      neurosurgery. After completing training, they join a pool of practicing
      neurosurgeons that includes about 3,260 board certified neurosurgeons and an
      additional 390 practicing neurosurgeons who are still in the certification
      process. The pool of active neurosurgeons does not increase by 135 surgeons each
      year since the forces of retirement and death serve to decrease it. Judging by
      the experience of some large Health Maintenance Organizations, who employ no more
      neurosurgeons than are necessary to supply their enrolled members, the net result
      is that the USA has at present about the proper number of neurosurgeons necessary
      to meet the needs of the country. No one can predict future needs for
      neurosurgeons with accuracy, and it is safer not to set the number of
      neurosurgeons based on a guess. We do need to restrict the number of trainees to
      that number we can train properly. The quality of our neurosurgeons needs to be
      maintained. Beyond that, the market place, however imperfect, is a better long
      term regulator of numbers than any governmental or privately-based committee.

PMID- 9253436
TI  - How many residents shall we train? The Netherlands experience.

PMID- 9253437
TI  - How many higher neurosurgical trainees shall we train in the British Isles?
AB  - In the British Isles there are a small number of neurosurgeons. The number of
      career trainees has been rigorously controlled over the years, such that there is
      a sufficient number to satisfy the number of new consultants required as the
      result of retirement and the creation of new posts. The number of career trainees
      posts is 89 but the current calculated requirement is for 112 career trainees. In
      addition overseas trainees come to the British Isles, usually for a specific part
      of their training.

PMID- 9253438
TI  - How many neurosurgeons do we want to educate in Europe annually? The Danish
      proposal.
AB  - The neurosurgical population consists of professors, consultants, specialised
      senior registrars, and doctors in training (senior registrars, trainees and young
      doctors to be educated as neurosurgeons). Knowing number and size of the
      neurosurgical departments in each European country, the number of staff members,
      the politics of retirement (age, educational level) and the age of every
      neurosurgeon it is possible to calculate the exact number of trainees needed per
      year to maintain a state of balance in every single European country. With
      Denmark as a model we based our assessments partly on a simple calculation model
      of the exact annual number of neurosurgical trainees or senior registrars and
      partly used an actuary flow model for calculation. In Denmark with 5
      neurosurgical departments, 5.2 mill. population and a retirement age of 70, we
      have an average of 1-2 newcomers per year and maintain a bulk of 10 senior
      registrars in education. Thus there will be a balance between intake of newcomers
      and retirement, of course with some unknown factors as unforeseen dismissal or
      resignation, death rate among neurosurgeons and transfer to private practice.

PMID- 9253439
TI  - How many residents shall we train? The Iberian experience.
AB  - The basic features of neurosurgical training in Portugal and Spain are described.
      Data include demographic characteristics, training requirements and accreditation
      criteria.

PMID- 9253441
TI  - How many residents shall we train--the situation in Germany.
AB  - The situation of training neurosurgeons in Germany is reviewed taking into
      consideration the current figures of finished residencies, the development in the
      number of training neurosurgical units in Germany, and the personnel and
      structure of a neurosurgery unit allowed to train. The jurisdiction for
      specialist training as well as typical problems encountered in training residents
      are being discussed. In 1992; 130,364 patients, equivalent to 0.94% of all
      patients in Germany were treated in 4.792 dedicated neurosurgical beds. A total
      of 644 working neurosurgeons were registered. Between 1986 and 1993, 349
      residents qualified as neurosurgeons, an average of 43.5 per year. 57% of
      neurosurgical units employ non-trainee junior doctors, 13% have no residents, and
      62% of departments trained less than one resident per year on average. Only 57%
      of units finish residency training always on time and only 79% of major units
      have full training permission. The figures provided in this article do not
      substantiate the assumption that we have trained too many specialists in the
      past. The problems which some residency programmes encounter however do suggest
      that it could be wise not to continue to train specialists at the same rate as in
      the past.

PMID- 9253440
TI  - Neurosurgical manpower in France.

PMID- 9253442
TI  - How many neurosurgeons should we train? The Japanese experience.

PMID- 9253443
TI  - Neurosurgical training at present and in the next century.

PMID- 9253444
TI  - The UEMS model--proposals for classification and training durations of
      specialties registered in doctors' directives. European Union of Medical
      Specialists.

PMID- 9253445
TI  - Contents and structure of a training program. The Japanese proposal.

PMID- 9253446
TI  - Neurosurgical training in Austria--present status and aspects for the future.

PMID- 9253447
TI  - A resident's experience and suggestion.

PMID- 9253448
TI  - "Control and structure of a training program." The view of a non-academic
      hospital.

PMID- 9253449
TI  - Assessment of training progress and examinations.
AB  - Board certification and accreditation of training programs began as measures of
      quality in the United States. Both functions were done initially by the American
      Board of Neurological Surgery (ABNS). In 1954, certification of trainees and
      accreditation of programs became separate functions in order to eliminate
      potential conflicts of interest. Currently, the ABNS certifies trainees who have
      completed neurological surgery training in an accredited program whose curriculum
      includes operative and nonoperative experience, have the endorsement of the
      training program director, and have passed the written in-training examinations
      and a final oral examination. Accreditation of training programs is a separate
      function administered by the Residency Review Committee (RRC) of the
      Accreditation Council for Graduate Medical Education. Individual programs are
      reviewed on a periodic basis for quality of the curriculum, facilities, faculty,
      and patient volume. The ABNS and the RRC are separate groups, both comprised of
      neurosurgeons with a strong commitment to the educational process.

PMID- 9253450
TI  - Experience with the EANS examinations.

PMID- 9253451
TI  - Experience with the United Kingdom examinations in neurosurgery.
AB  - The UK Intercollegiate Specialty Board examination in Surgical Neurology was
      established in 1991 based on the experience of the original Royal College of
      Surgeons of Edinburgh Assessment in Surgical Neurology, an exit examination that
      was originally opposed both by surgery in general and by the younger
      neurosurgical community. Criteria for eligibility encompass both UK, EC and non
      EC overseas graduates. Candidates must have completed satisfactorily their 4th
      year of a 6 year training programme, have personal experience with the more
      straightforward benign tumours, aneurysms and posterior fossa explorations, and
      be able to safely manage a conventional neurosurgical practice. The examination
      consists of a multiple choice question paper, clinical examination and three
      Vivas. A curriculum is under construction. Examinations are held twice per annum,
      and rotate between the four colleges. There are strict guidelines for the
      examiners. The pass rate is about 70%. All aspects of the examination continue to
      evolve and are carefully audited.

PMID- 9253452
TI  - Periodic evaluation of training progress and teaching.

PMID- 9253454
TI  - When should residents be exposed to research?
AB  - In this paper the planning of research in a neurosurgical training program is
      discussed. There are good arguments to organize research rotation after one or
      two years of clinical exposure rather than at the beginning or the end of the
      program. Teacher as well as resident can prepare the rotation more carefully
      selecting the topic according to abilities and interests, selecting a suitable
      research institution, and prepare funding if necessary. The goals of a research
      rotation, the various categories of basic and applied research, and the length of
      the research period are being treated.

PMID- 9253455
TI  - Role of surgical research in the training of neurosurgeons.

PMID- 9253453
TI  - What consequences should result from failure to meet internal standards?
AB  - This paper tries to approach a difficult problem, namely how to deal with a
      resident who has failed to meet the internal standards of a residency training
      program. First the problems of the definition of a standard and the associated
      problems of its reproducibility, documentation, teaching, update, and internal
      variability inside the same teaching program are dealt with. Consequently the
      question needs to be answered that constitutes a failure to meet the standard.
      The results of a survey of residents' attitudes are quoted as are some responses
      to a survey among the chiefs of teaching programs. Considering the attitudes of
      residents on how to handle breaches of standard the basic message was that
      residents want to be told that they do not function. Both parties want the
      collaboration of senior staff members on this topic. Whereas residents want to re
      train, exercise and talk they do not want sanctions. Chiefs, however, want much
      less re-training, exercising and talking but earlier sanction. The difficult
      point of dealing with a true failure is discussed in the light of the German
      legal situation and the actual possibilities of how to handle the case. Before it
      comes to the point of discontinuing the training of a resident, it needs to be
      agreed upon what would be a classical situation of failure in which both the
      chiefs responsible for training and the residents agree that training is better
      discontinued. The author describes his experience with the real course of events
      in 7 cases he witnessed in 22 years.

PMID- 9253456
TI  - Research in neurosurgical training: clinical reviews and trials.
AB  - A well prepared intellectual basis is at least as important as a sound technical
      training for a safe, successful Neurosurgeon. Correct decisions depend as much
      upon clinical information and experience as upon biomedical theory and an
      appreciation of the science of real life clinical research is more valuable than
      experience in laboratory techniques. Understanding of what makes up a good study,
      providing a reliable basis for clinical practice, is best gained through the
      training conducting personal research. The training must provide an enquiring,
      motivating, intellectual environment, as well as disciplined organisation and
      support. Successful clinical research is difficult and demanding but is one of
      the clearest testimonies to the quality of both trainer and trainees.

PMID- 9253457
TI  - From the scientific idea to its realisation--principles and strategies in
      neurosurgery.

PMID- 9253458
TI  - Subspeciality training in neurosurgery.
AB  - Evolution for neurosurgeons is not at a standstill. The environment, competition
      from neighbouring fields, advances in biology and changes in the level of
      information available to our patients, the "market" will favour and demand
      subspecialisation. Subspecialists are characterized by recognized records of
      excellence. The best suited to impart knowledge to a clinical fellow is the
      senior subspecialist who is working within a group of other complementary
      subspecialists. To develop subspecialty expertise takes a minimum of one,
      preferably two years of training. Neurosurgery will retain and regain its
      strength as a discipline by diversification, not by clinging to monolithic
      uniformity.

PMID- 9253459
TI  - Neurosurgical spine fellowships: the Phoenix model.

PMID- 9253460
TI  - A model fellowship in pediatric neurosurgery.

PMID- 9253461
TI  - Post residency subspecialty training in neurosurgery--the impact of subspecialty
      training on organized neurosurgery and resident training--benefits,
      responsibilities and liabilities.

PMID- 9253462
TI  - In the realm of ideas: the advent of advanced surgery of the human cerebrum and
      neurosurgical education.
AB  - High technology has recently exerted remarkable positive forces within the field
      of neurological surgery. Striking developments in brain imaging, stereotaxy,
      molecular biology, radiation physics and complex data management promise to
      revolutionize surgery of the human cerebrum. These changes are not without
      profound impact on national health care economics and present enormous
      philosophical and educational challenges which will create considerable turmoil
      over the next decades.

PMID- 9253463
TI  - The development of training systems in general surgery.

PMID- 9253464
TI  - Interactive multimedia software for training and education in neurosurgery.
AB  - Medicine with its abundance of facts and richness of imaging techniques has
      always been adopting new technologies to improve teaching and training. As a
      natural consequence, the use of computer-based multimedia technology is generally
      increasing in medicine and also reaching the field of neurosurgery. Especially
      the use of interactive multimedia technology seems promising to improve training
      and education and increase accessibility of highly specific material.

PMID- 9253465
TI  - A comparison of the efficacy and safety of inhaled corticosteroids in asthma.

PMID- 9253466
TI  - Cellular and molecular studies of atherogenesis.
AB  - The lesions of atherosclerosis represent a protective, inflammatory
      fibroproliferative response against the different agents which can cause the
      disease. With a chronic insult, the response may become excessive and thus
      constitute part of the disease process. The excessive response may be reversed,
      given sufficient opportunity for modification of the injurious factors.
      Approaches to modifying specific cellular interactions, growth-regulatory
      molecules or intracellular signaling molecules may afford opportunities for
      lesion prevention or regression. For further reading see [1,2].

PMID- 9253467
TI  - A critical look at the evidence for the oxidation of LDL in atherogenesis.

PMID- 9253468
TI  - Immunological response to oxidized LDL.

PMID- 9253469
TI  - Mechanical determinants of plaque modeling, remodeling and disruption.

PMID- 9253470
TI  - Mechanisms involved in endothelial responses to hemodynamic forces.

PMID- 9253471
TI  - Phagocyte implications in advanced atherosclerosis.

PMID- 9253472
TI  - Mechanisms of leukocyte activation in the circulation.

PMID- 9253473
TI  - Pentoxifylline: its influence on the interaction of blood cells with the vessel
      wall.
AB  - PTX counteracts the increased microvessel permeability which is a feature of the
      inflammatory aspect of atherogenesis. Furthermore, PTX inhibits oxLDL-induced
      leukocyte adhesion and, via its positive influence over fibrinolysis and anti
      aggregatory factors (e.g. prostacyclin), inhibits thrombus formation. PTX thereby
      preserves the integrity of the walls of the microcirculatory blood vessels, while
      reducing the likelihood of thrombosis and its potentially life-threatening
      sequelae.

PMID- 9253474
TI  - Epidemiology of peripheral vascular disease.

PMID- 9253475
TI  - Socioeconomic impact of peripheral vascular disease.

PMID- 9253476
TI  - Quality of life assessment in peripheral arterial disease.

PMID- 9253477
TI  - Clinical experience with pentoxifylline.

PMID- 9253478
TI  - Transient evoked otoacoustic emissions in newborns in the first 48 hours after
      birth.
AB  - Newborns are often discharged from hospital at the age of about 48 hours. At this
      age, transient evoked otoacoustic emissions (TEOAEs) are not necessarily
      recordable in all healthy newborns. In order to determine the factors which would
      enable the successful recording of TEOAEs before discharge to facilitate
      screening for hearing, 65 fullterm newborns under 48 hours of age were tested,
      the youngest being 10 hours old. The ears of those neonates in whom TEOAEs could
      not be obtained (N = 7 neonates bilaterally, 6 unilaterally) were examined
      otoscopically, cleaned of vernix and retested for TEOAEs. We were thus able to
      record in at least one ear in all neonates tested, if the ears were clean, if
      they were asleep and if the testing room was quiet.

PMID- 9253479
TI  - Hair cell loss from acoustic trauma in chloroquine-treated red, black and albino
      guinea pigs.
AB  - In order to further elucidate the relationship between noise-induced hearing loss
      and pigmentation, a two-factor study was designed. Albino, red and black guinea
      pigs were divided into controls and chloroquine-treated groups and exposed to 1
      kHz noise, 105 dB SPL, for 72 hours. One month later the animals were sacrificed
      and the loss of hair cells evaluated. The red guinea pigs developed a greater
      hair cell loss (OHC) in all three OHC rows than black or albino animals. Black
      and albino groups showed equal amounts of OHC loss. A high dosage of chloroquine
      seemed to reduce the OHC loss in albino, but not in black or red guinea pigs. The
      greater OHC loss in red compared with black animals is in accordance with the
      original hypothesis that melanin protects the inner ear against noise trauma.
      However, as red guinea pigs developed greater OHC loss than albinos, it is
      obvious that the original hypothesis needs to be modified to consider also the
      different melanin types, i.e., the black eumelanin and the red pheomelanin. The
      present results are interpreted as a toxic interaction in the strial melanocytes
      between pheomelanin and noise. It is suggested that the pathophysiology of noise
      induced hearing loss involves cochlear mechanisms related to radical oxygen
      species (ROS) as melanin both generates and neutralizes ROS. A hypothesis about a
      linkage between dopamine, noise trauma and the cochlear melanocyte system is
      discussed.

PMID- 9253480
TI  - Single unit activity in the inferior colliculus of the rat elicited by electrical
      stimulation of the cochlea.
AB  - The activity of single neurons (n = 182) of the central nucleus of the inferior
      colliculus (CIC) of the rat was recorded in response to unilateral electrical
      stimulation of the left cochlea and/or acoustical stimulation of the right ear.
      The probability of response to both modes of stimulation was comparable (90 per
      cent for contralateral and 60 per cent for ipsilateral presentation). Response
      patterns consisted predominantly of onset excitations. Response latencies to
      electrical stimuli ranged from 3 to 21 ms, with an average value of 9.7 ms (SD =
      3.5 ms) in the ipsilateral CIC and 6.6 ms (SD = 3.4 ms) in the contralateral CIC.
      With respect to binaural inputs, the majority of units were excited by
      stimulation of either ear (EE; about 60 per cent) while about one third were
      influenced by one ear only (EO). Units excited by one ear and inhibited by the
      other (EI) were rare. The main difference between the present implanted rats and
      normal animals was the virtual absence here of inhibitory effects for both types
      of stimuli when they were delivered to the ipsilateral ear (very few EI units).

PMID- 9253482
TI  - The Landau-Kleffner syndrome: increased understanding.
AB  - The Landau-Kleffner and the continuous spike and wave discharges during slow
      sleep (CSWS) syndromes are described and possible links between the two are
      discussed. They certainly overlap, with clinical and electroencephalographic
      features in common. Potential causes are discussed. There is seldom a definite
      reason for the seizures but it way well be that the spike and wave discharges
      seen in the EEG, whatever their origin, may disrupt the development of language
      and cognitive function at a critical stage. If neurons and axons are involved in
      this disorganized activity they surely cannot perform normally. The evidence that
      these discharges in the Landau-Kleffner syndrome can have a focal origin in areas
      important for language supports this hypothesis. Certain variations among studies
      quoted may be due to factors such as age of onset, the duration of the paroxysmal
      activity, its intensity and especially its localization. Also, if development has
      been distorted subsequent progress is likely to be disturbed after the primary
      condition has ceased to exist. The diagnosis can sometimes present difficulties,
      for example from deafness, psychiatric condition, post-ical dysphasia and from
      progressive degenerative neurological disorders. If the possible role of the
      epileptic activity is accepted, there are strong reasons for advocating anti
      epileptic treatment, even if overt seizures are rare. The response to drugs is
      varied. Fits will usually stop, but not so often the spike and wave discharges,
      and it is justifiable to try various regimes. Subpial resection has been reported
      to be successful, possibly by preventing the cortex generating seizures, and
      their spread.

PMID- 9253481
TI  - Audiometric patterns of genetic non-syndromal sensorineural hearing loss.
AB  - Sixty-five families with non-syndromal sensorineural hearing loss (NS-SNHL) of
      genetic aetiology were subtyped according to Gorlin et al. Individual audiogram
      shapes were also classified in order to detect inter- and intra-familial
      variations. In 48 families with an Autosomal Dominant (AD) inherited form, 26
      exhibited the features of (high-frequency) progressive NS-SNHL, 12 those of mid
      frequency NS-SNHL, 5 were affected by congenital low-frequency NS-SNHL; 1 kindred
      showed a progressive low-frequency pattern and another 1 a unilateral NS-SNHL;
      only 3 kindreds were affected by severe congenital NS-SNHL. Autosomal Recessive
      (AR) inherited forms were composed of 9 kindreds with severe congenital NS-SNHL,
      and 7 with moderate congenital NS-SNHL. One X-linked form was identified. AD- and
      AR-inherited NS-SNHL differed significantly both in severity of hearing
      impairment and in audiogram shapes. With few exceptions, in each family
      classified according to Gorlin, most of the affected subjects shared the same
      audiogram profile. Intrinsic progression of the disease versus ageing was studied
      in the larger subtype of individuals with the high-frequency loss. Gorlin's
      classification still remains the best system to classify NS-SNHL, and can provide
      a broad base to separate a very heterogeneous group of disorders. Results
      obtained in gene mapping in single large human families or in homologous gene
      search could be tested in our families. For some of them, namely those with high
      frequency progressive and low-frequency NS-SNHL, testing should already be
      feasible.

PMID- 9253483
TI  - Leukocytes in neuronal ceroid-lipofuscinoses: function and apoptosis.
AB  - The neuronal ceroid-lipofuscinoses (NCL) are a group of progressive
      encephalopathies with a fatal course that are mostly of autosomal recessive
      inheritance. The pathophysiological mechanisms causing the diseases are not
      known. The characteristic histomorphological feature of the NCL is an abnormal
      lysosomal accumulation of lipopigments in neural and extraneural cells, including
      peripheral blood leukocytes. We studied the function of peripheral venous blood
      immunocompetent cells in ten patients with NCL and in age- and sex-matched
      controls to determine how, if at all, the accumulation of intracytoplasmic
      storage material influences the functional capacity of affected tissue. Our
      results did not reveal any functional impairment of affected cells, but rather
      suggested a higher turnover rate in NCL. Apoptosis was increased, suggesting that
      abnormally controlled programmed cell death might play an important role in the
      pathogenesis of NCL.

PMID- 9253484
TI  - Single dose immunoglobulin therapy for childhood Guillain-Barre syndrome.
AB  - To establish the efficacy of intravenous immunoglobulins (IVIG) in the treatment
      of acute Guillain-Barre syndrome (GBS), we treated nine consecutive pediatric
      cases (age 2.5-13.5 years) fulfilling the criteria for GBS with a single dose of
      IVIG (Sandoglobulin; 2 g/kg/BW). None of the patients experienced any IVIG
      related side-effects. The mean time required to improve by at least one grade on
      the functional GBS scale after IVIG treatment was 3.5 days, while the mean period
      to regain ambulation was 11.2 days. Full mobilization without evidence of relapse
      in the follow-up period (mean 14.5 months) was noted in all but one patient who
      relapsed after 5 months. We conclude that the early use of a single IVIG dose may
      prevent further progression of the disease, thus shortening the clinical course
      of childhood GBS. The most beneficial IVIG dose regimen remains to be determined
      by controlled trials.

PMID- 9253485
TI  - Brief post-hypoxic-ischemic hypothermia markedly delays neonatal brain injury.
AB  - The influence of post-insult temperature modulation on ischemic injury in
      immature brain was studied in 7-day-old rats that underwent a unilateral carotid
      artery ligation followed by exposure to hypoxia in 8% oxygen at an ambient
      temperature of 36.5 degrees C. After the hypoxic exposure, the animals were
      separated into three groups and placed for 3 h in temperature-controlled
      incubators set at 32 degrees C, 35 degrees C, and 38 degrees C. In Study 1, the
      influence of post-insult temperature modulation was assessed after graded
      cerebral hypoxic-ischemic injury. Brain damage was assessed 1 week after the
      insult by comparison of wet weights in the cerebral hemispheres ipsilateral and
      contralateral to the carotid artery ligation. Rectal temperatures of the animals
      significantly correlated with extent of brain injury after 60 min (Spearman
      correlation coefficient, p = 0.44, P = 0.005) and 90 min (p = 0.46, P = 0.004)
      but not 120 min of hypoxia (p = 0.18, P = 0.46). In Study 2, animals were exposed
      to 75 min hypoxia, and injury was assessed morphometrically and histologically at
      1 and 4 weeks after the injury. Rectal temperatures significantly correlated with
      the extent of ischemic injury in the cerebral cortex (p = 0.3, P = 0.046) and
      striatum (p = 0.3, P = 0.048) at 1 week, but not 4 weeks, after the insult. The
      findings indicate that post-insult hypothermia delayed the expression of mild to
      moderate brain damage by more than a week, after which the damage was as severe
      as in normothermic animals. The results indicate that the events that determine
      the final expression of a neonatal hypoxic-ischemic insult can be extended over a
      long interval by post-insult hypothermia.

PMID- 9253486
TI  - CSF ACTH and beta-endorphin in infants with West syndrome and ACTH therapy.
AB  - Corticotrophin (adrenocorticotropic hormone, ACTH) and beta-endorphin levels of
      the cerebrospinal fluid (CSF) were determined in 16 infants with the West
      syndrome during individualized ACTH treatment. Prior to treatment, the levels of
      CSF ACTH were significantly higher in infants with cryptogenic spasms, normal
      perinatal events, or normal development than in infants with symptomatic spasms
      or delayed development. The CSF beta-endorphin levels did not differ among the
      groups. At response, the infants could be divided into three groups: (1) short
      course, low-dose responders with a substantial CSF ACTH decline, (2) long-course,
      high-dose responders with no such effect (but with a tendency towards an upward
      incline), and (3) non-responders with no significant CSF ACTH changes. The
      changes in CSF beta-endorphin were somewhat similar to the changes in CSF ACTH,
      but the greater variability did not allow statistical significance.

PMID- 9253487
TI  - Delayed appearance of interictal EEG abnormalities in early onset childhood
      epilepsy with occipital paroxysms.
AB  - Childhood epilepsy with occipital paroxysms is an age-related idiopathic focal
      epilepsy. Occipital EEG paroxysms are considered necessary for diagnosis. We
      carried out a close clinical and EEG follow-up (range, 2-12 years; mean, 6 years
      7 months; median, 7 years) in 24 patients (age range, 4-19 years; mean, 11 years
      8 months; median, 11 years). In five children with early seizure onset and
      particularly benign prognosis without any treatment, EEG abnormalities appeared 3
      10 months after the first seizure. Four of them exhibited the ictal pattern of
      versive seizures with vomiting. Our findings confirm that in the early idiopathic
      focal seizure disorders, interictal EEG abnormalities may be lacking at the
      beginning of the disorder.

PMID- 9253489
TI  - Perioral myoclonia with absences? A case report with EEG and voltage mapping
      analysis.
AB  - The author presents clinical and electroencephalographic data of an epileptic
      girl, whose absences started at the age of 2. Based on seizure semiology, serial
      EEG and video-EEG recording, 7 years of follow-up and other clinical data, the
      patient was diagnosed as having the PMA ('perioral myoclonus with absences')
      syndrome. There were some disagreement between clinical and EEG data, however.
      Finally, she became completely seizure free on valproate+lamotrigine medication.
      Detailed EEG and voltage mapping analysis disclosed that spike movements of ictal
      and interictal generalized spike-wave discharges showed always the same, very
      consistent, peculiar topographic pattern. This pattern was fundamentally
      different from spike patterns associated with typical absence seizures (recorded
      in other patients). Analysis of clinical, EEG and voltage mapping results-suggest
      that actually this case might be rather classified as myoclonic epilepsy. The
      conjunction of this case to the PMA syndrome has been discussed.

PMID- 9253488
TI  - Immunohistochemical demonstration of cytokeratin in human embryonic neurons
      arising from placodes.
AB  - Sensory neurons of the olfactory, trigeminal, facial, vestibulo-cochlear,
      glossopharyngeal and vagal nerves, and neurons migrating along the olfactory
      nerve to the brain have special anlagen, made up of placodes located in the
      epithelial layer. To investigate the characteristic phenotype of placode-derived
      neurons, immunohistochemical analysis of intermediate filaments was conducted on
      formalin-fixed human embryonic tissues. Neurons arising from placodes including
      luteinizing-hormone releasing hormone (LHRH) neurons migrating from the olfactory
      placode to the brain had immunoreactivity to antibodies specific to cytokeratin,
      AE1 and CAM5.2 during the embryonic stage. However, this immunoreactivity
      disappeared during the late embryonic to the post-embryonic stage and was not
      observed in the roots of these nerves in the post-natal stage. Immunoreactivity
      was detected in both the somata and processes, and the distribution differed from
      that described in rodent brain neurons. With this exception, no other human
      peripheral neurons, including spinal dorsal root ganglia, had immunoreactivity
      with anti-cytokeratin antibodies throughout the entire developmental stage.
      Although the cephalic neural crest also directly generates neurons to most of the
      cranial sensory ganglia, we could not find any evidence that it contributed to
      the genesis of cytokeratin-positive embryonic neurons. We concluded that
      cytokeratin is an intermediate filament common to human embryonic neurons of
      cephalic placodal origin and that this immunohistochemical marker may be useful
      in analyzing the developmental sequence of several congenital diseases involving
      the cranial nerves, such as Moebius syndrome and Goldenhar syndrome.

PMID- 9253490
TI  - Rare combination of Becker muscular dystrophy and Klinefelter's syndrome in one
      patient.
AB  - Becker muscular dystrophy (BMD) was diagnosed in a male patient with
      Klinefelter's syndrome (47, XXY karyotype). The BMD was confirmed by (i)
      immunohistological methods and Western blotting, showing decreased quantity of
      dystrophin in muscle biopsy specimen and (ii) molecular genetic analysis which
      demonstrated a homozygous deletion of exons 45-47 within the dystrophin gene on
      both X-chromosomes. The same deletion was found on one of the X-chromosomes in
      the patient's mother. It can be deduced therefore that Klinefelter's syndrome in
      this patient is most likely due to a non-disjunctional error which occurred
      either during the second maternal meiotic division or during early postzygotic
      mitotic divisions.

PMID- 9253491
TI  - Congenital familial myopathy with type 2 fiber hypoplasia and type 1 fiber
      predominance.
AB  - A 12-month-old girl with delayed developmental milestones, due to muscle
      hypotonia and weakness from early infancy, exhibited type 2 fiber hypoplasia. A
      muscle biopsy specimen disclosed type 1 fiber predominance and type 2B fiber
      deficiency compatible with congenital myopathy. During the following 4 years, she
      continued to have mild muscle weakness, but no mental retardation. Her mother had
      similar symptoms from early infancy with minimal progression. Although type 2
      fiber hypoplasia is a non-specific finding in various diseases, it may be a
      specific finding in a limited number of patients with hereditary congenital non
      progressive myopathy.

PMID- 9253492
TI  - Heat stroke-like episode in a child caused by zonisamide.
AB  - A 2-year-old mentally retarded boy with frontal lobe epilepsy presented with an
      episode that resembled heat stroke during the administration of zonisamide. He
      developed hyperpyrexia with oligohidrosis and central neurological symptoms,
      including, chorea-like involuntary movements, resting tremor, and cogwheel
      rigidity. A sweat test using pilocarpine iontophoresis revealed a marked
      reduction in the sweat response, which suggested a postganglionic sweating
      dysfunction. A skin biopsy examined by light and electron microscopy showed no
      morphological abnormality in the sweat glands. The oligohidrosis caused by
      zonisamide was reversible in that the patient regained the ability to sweat
      within 2 weeks of the cessation of drug administration. Children receiving
      zonisamide should be monitored for oligohidrosis and the development of
      neurological symptoms associated with an elevation of body temperature.

PMID- 9253493
TI  - Quality control for hospitals' clinical ethics services: proposed standards.

PMID- 9253494
TI  - Liability of ethics consultants: a case analysis.

PMID- 9253495
TI  - Non-heart-beating cadaver procurement and the work of ethics committees.

PMID- 9253496
TI  - Wisconsin healthcare ethics committees.

PMID- 9253497
TI  - Ethics in the outpatient setting: new challenges and opportunities.

PMID- 9253499
TI  - CQ sources/bibliography.

PMID- 9253498
TI  - Ethics without walls: the transformation of ethics committees in the new
      healthcare environment.

PMID- 9253500
TI  - Treating the patient to benefit others.

PMID- 9253501
TI  - Goldilocks and Mrs. Ilych: a critical look at the "philosophy of hospice".

PMID- 9253502
TI  - Reassessing the reliability of advance directives.

PMID- 9253503
TI  - Teaching the virtues: justifications and recommendations.

PMID- 9253505
TI  - Individual autonomy and collective decisionmaking.

PMID- 9253504
TI  - Developing habits and knowing what habits to develop: a look at the role of
      virtue in ethics.

PMID- 9253506
TI  - The effect of promoter strength in adenoviral vectors containing herpes simplex
      virus thymidine kinase on cancer gene therapy in vitro and in vivo.
AB  - The use of adenoviral vectors to deliver the herpes simplex virus thymidine
      kinase (HSVtk) gene followed by treatment with the prodrug ganciclovir (GCV) has
      promise for a variety of applications where excess cell proliferation is
      detrimental such as treatment of tumors and vascular restenosis. Optimizing this
      system is thus an important goal. The purpose of this study was to determine if
      the induction of higher levels of HSVtk expression would augment the sensitivity
      to GCV. This was accomplished by generating adenoviral vectors that expressed
      HSVtk from promoters of different efficiencies (the CMV versus RSV promoters).
      Despite higher levels of HSVtk expression per cell with the CMV promoter, there
      was no significant enhancement of antitumor effects between RSV- and CMV-driven
      adenovirus vectors in in vitro and in vivo studies indicating that simply
      increasing HSVtk enzyme levels per cell above a minimal threshold level will not
      be effective in augmenting the HSVtk/GCV system. These results suggest that other
      strategies, e.g., the use of higher doses of GCV, augmentation of the "bystander
      effect," the generation of mutant HSVtk genes with higher substrate affinities,
      the discovery of improved vectors with increased transduction efficiencies, or
      the development of new prodrugs with higher affinities for HSVtk will therefore
      be needed to enhance therapeutic responses.

PMID- 9253507
TI  - Defective herpes simplex virus vectors expressing thymidine kinase for the
      treatment of malignant glioma.
AB  - Viral vectors used for cancer gene therapy have usually been either replication
      incompetent vectors expressing a gene product that leads to the destruction of
      the tumor or replication-competent vectors that are inherently cytotoxic to the
      tumor cells. We have sought to combine the attributes of these different
      approaches using a defective herpes simplex virus (HSV) vector that consists of a
      defective particle, containing tandem repeats of the HSV thymidine kinase (TK)
      gene, and a replication-competent, non-neurovirulent HSV mutant as a helper
      virus. HSV-TK activity in defective vector-infected cells was significantly
      greater than that in helper virus-infected cells which contained a single copy of
      HSV-TK. Infection of cells with this defective vector renders them, as well as
      surrounding uninfected cells, sensitive to killing by ganciclovir. Ganciclovir
      treatment of C57BL/6 mice bearing TK-defective vector/helper virus-infected
      subcutaneous GL261 gliomas resulted in significantly decreased tumor size.

PMID- 9253508
TI  - Sensitization of colorectal and pancreatic cancer cell lines to the prodrug 5
      (aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) by retroviral transduction and
      expression of the E. coli nitroreductase gene.
AB  - Expression of genes encoding prodrug-activating enzymes can increase the
      susceptibility of tumor cells to prodrugs, and may ultimately achieve a better
      therapeutic index than conventional chemotherapy. CB1954 is a weak,
      monofunctional alkylating agent which can be activated by Escherichia coli
      nitroreductase to a potent dysfunctional alkylating agent which crosslinks DNA.
      We have inserted the nitroreductase gene into an LNCX-based retroviral vector, to
      allow efficient gene transfer and expression in colorectal (LS174T) and
      pancreatic (SUIT2, BxPC3, and AsPC1) cancer cell lines. A clone of LS174T cells
      expressing nitroreductase showed > 50-fold increased sensitivity to CB1954, and
      nitroreductase-expressing clones of pancreatic tumor lines were up to
      approximately 500-fold (SUIT2) more sensitive than parental cells. Concentrations
      of CB1954 minimally toxic to nontransduced cells achieved 100% cell death in a
      50:50 mix of parental cells with SUIT2 cells expressing nitroreductase; and
      marked "bystander" cell killing was seen with just 10% of cells expressing
      nitroreductase. Significant bystander cell killing was dependent on a high cell
      density. In conjunction with regional delivery of vectors and tumor selectivity
      of cell entry and/or gene expression, nitroreductase and CB1954 may be an
      attractive combination for prodrug-activating enzyme gene therapy of colorectal
      and pancreatic cancer.

PMID- 9253509
TI  - The influence of the p53 codon 72 polymorphism on ovarian carcinogenesis and
      prognosis.
AB  - The frequency of dysfunction of the p53 tumor suppressor gene in cancer has made
      the concept of gene replacement therapy with wild-type p53 an attractive
      strategy. Codon 72 of the p53 gene is highly polymorphic with a reported
      arginine/proline allelotype frequency of 0.65/0.35 for Caucasians and a reversal
      of this ratio in African-Americans. Ovarian cancer is more common and less
      aggressive in Caucasians. The arginine and proline alleles have different
      biochemical properties. Thus, we have hypothesized that these alleles may also
      have different biologic properties that could make one superior to the other for
      gene replacement therapy. To test this hypothesis in vivo, we investigated the
      prevalence of each allelotype in a population of 190 Midwestern American women
      with ovarian cancer and 52 healthy controls without a family history of cancer.
      We have found that: (1) the heterozygous arginine/proline allelotype is more
      common in probands with borderline cancers than in probands with invasive cancers
      (P = .0001) or healthy controls (P = .005); (2) despite a survival advantage (P =
      .006), probands homozygous for the arginine allele developed ovarian cancer at an
      earlier age (P = .01); (3) the frequency of tumor p53 mutations was independent
      of the germline p53 allelotype, but (4) when a loss of heterozygosity occurred in
      probands with invasive disease, the proline allele was lost preferentially (P =
      .002), and (5) any tumor which retained a proline allele was more prone to
      mutation (P = .04) than a tumor without a proline allele. Our results suggest
      that variation in the p53 codon 72 allelotype is an example of an intermediate
      risk polymorphism which interacts with epigenetic factors to play a role in
      ovarian carcinogenesis and may differentially influence cellular DNA repair and
      apoptotic pathways. These findings may have important ramifications in the choice
      of wild-type p53 genotype for gene replacement therapy of ovarian cancer.

PMID- 9253510
TI  - An HSVtk-mediated local and distant antitumor bystander effect in tumors of head
      and neck origin in athymic mice.
AB  - The "bystander effect," produced by ganciclovir-mediated killing of cells
      transduced with a herpes simplex virus thymidine kinase (HSVtk) gene, defines the
      cooperative killing of non-HSVtk-transduced cells. In vitro, a major contributor
      to this phenomenon is metabolic cooperation involving transfer of cytotoxic small
      molecules between cells via gap junctions. In this study, the bystander effect
      was assessed in vivo using cells of oral squamous cell carcinoma origin. Mixtures
      of HSVtk+ and HSVtk- tumor cells were implanted subcutaneously in the left flank
      of nude mice, and naive HSVtk- cells were implanted subcutaneously in the right
      flank. When tumors attained a size of 0.5 to 1 cm, the animals were treated with
      ganciclovir on a daily basis. The tumors comprised of mixed cells in the left
      flank resolved, consistent with a predicted bystander effect. The naive tumors in
      the right flank either resolved or became cytostatic showing little further
      growth compared to controls. Similar results were obtained when naive tumors were
      grown in both flanks and the tumor in the left flank received intratumoral
      injection of HSVtk retroviral producer cells or PA317 (HSVtk+) packaging cells,
      but not parental NIH 3T3 cells. Concomitant treatment with dexamethasone impaired
      the antitumor effect on the contralateral side. When these experiments were
      performed in SCID-Beige mice, there was a reduced antitumor effect on the
      ipsilateral flank and no antitumor response in the contralateral flank. Together
      with histology of regressing tumors, which showed an infiltration of lymphoid
      cells, these results are suggestive of an immune-related antitumor response that
      could account for the distant bystander effect.

PMID- 9253511
TI  - In vivo gene inoculation of a recombinant single-chain antitumor antibody induces
      anti-immunoglobulin response.
AB  - While in vivo gene inoculation is being increasingly exploited to express genes
      of choice and elicit specific immune responses in animal models, the utility of
      this method has not been explored extensively for the expression of antibody
      genes. The primary constraint of this method is the need to deliver to, and
      express in, a single cell two functional genes, i.e., those encoding heavy and
      light chains of an antibody molecule. Several single-gene constructs encoding
      variants of the monoclonal antibody (MAb) CC49 have been developed, MAb CC49
      recognizes a tumor-associated glycoprotein, TAG-72. SP2/O myeloma cells,
      transfected with the CC49 single gene, express a single-chain protein which is
      secreted by the transfectoma as a homodimer. Following intramuscular injection of
      mice with the expression plasmids of the single-gene constructs, the encoded CC49
      antibody (AB1) was detected in the plasma of the host. In addition, cellular and
      humoral immune responses to AB1 have been demonstrated. Antibodies (AB2) to the
      in vivo-produced variable region of AB1 have been detected and persisted for at
      least 70 days post-inoculation of the recombinant plasmid. Thus, in vivo gene
      inoculation of single-chain immunoglobulins may be an alternative or
      complimentary approach to the induction of anti-idiotypic responses in
      immunotherapy protocols.

PMID- 9253512
TI  - Increase of cytotoxic sensitivity of primary human melanoma cells transfected
      with the interleukin-7 gene to autologous and allogeneic immunologic effector
      cells.
AB  - Patients with metastatic melanoma have a very poor prognosis. In many cases, the
      tumor recurs after surgical excision. Therefore, it might be beneficial for
      cancer patients to induce an immune attack against the tumor by inserting a
      cytokine gene into the tumor cells. Here, 14 primary cell cultures could be
      established from 45 patients with malignant melanoma. Primary cell cultures were
      transfected via electroporation with the gene encoding for human interleukin-7
      (IL-7). Transfection resulted in the production of biologically active IL-7 with
      an average of 850 pg/mL per 10(6) cells per 24 hours. Irradiation with 10,000
      cGy, which inhibited tumor cell growth in vitro, increased the amount of released
      IL-7 to an average amount of 1050 pg/mL per 10(6) cells per 24 hours. No
      significant differences in the phenotype were observed in the IL-7-transfected
      cells compared with nontransfected cells. The expression of HLA class I and II,
      ICAM-1, and of a melanoma-associated antigen remained unaltered. Transfection
      with IL-7 had no significant effect on the proliferation of melanoma cells as
      measured in a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]
      assay. There was no significant change in the cytokine profile after transfection
      or irradiation of the cells, but one cell culture expressed a high amount of IL-6
      (about 2 ng/mL). IL-6 was expressed in nontransfected cells and was not altered
      by transfection. Interestingly, transfected cells from primary melanoma cultures
      possessed a higher sensitivity to immunologic effector cells compared with
      nontransfected cells. This was true for allogeneic as well as autologous melanoma
      cells. Our results show the feasibility of a gene transfer into primary human
      melanoma cells, different from retroviral transduction. IL-7-transfected cells
      might be of value in vaccination protocols for melanoma patients.

PMID- 9253514
TI  - Evaluation of i-STAT portable clinical analyzer in a neonatal and pediatric
      intensive care unit.
AB  - OBJECTIVE: To evaluate the Point-of-Care (POC) i-STAT system for measuring blood
      gases (pH, pCO2, pO2) and whole blood electrolytes (sodium, Na+, potassium, K+
      and ionized calcium, iCa2+) in the neonatal and pediatric intensive care units.
      DESIGN AND METHODS: The i-STAT system was evaluated for imprecision, necessity of
      running quality control and accuracy. Comparison of patients' samples analyzed by
      the i-STAT system and the Ciba Coming 288 blood gas analyzer were performed. The
      reliability of the i-STAT system when performed by non-laboratory personnel was
      assessed. RESULTS: The system was evaluated for imprecision and linearity using
      three concentrations of aqueous standards. Except for pO2, the %CVs were < 3.0
      for all the analytes (pH, pCO2, Na+, K+ and iCa2+) at all the three
      concentrations. Using whole blood studies the precision data gave %CVs that were
      < 3.5 for all the analytes. Linearity studies showed good linearity over the five
      different concentrations tested. Comparison of the i-STAT and the Ciba Coming 288
      blood gas analyzer was assessed by split sample measurement. Patients' results
      from the i-STAT correlated well with the Ciba Coming 288 blood gas analyzer (r =
      0.99 for pH, pCO2 and pO2 and 0.95 to 0.99 for Na+ and K+) with the exception of
      iCa2+ (r = 0.73). There was no significant difference in the results when
      operated by PICU/NICU nurses or laboratory personnel. A further study was made to
      assess whether routine quality control (QC) samples are necessary when using the
      i-STAT system. The regression analysis (slope and correlation coefficient) of the
      results from instruments run with and without QC samples gave results close to 1,
      indicating that there is no need to run additional quality control (QC).
      CONCLUSION: The POC testing analyzer i-STAT is a reliable alternative to the
      traditional blood gas analyzers and provides marginal improvement in turnaround
      time when compared with the service received from the PICU/NICU laboratory. Costs
      need to be carefully controlled.

PMID- 9253513
TI  - Selective augmentation of radiation effects by 5-fluorocytosine on murine
      B16(F10) melanoma cells transfected with cytosine deaminase gene.
AB  - We report that in vitro 5-fluorocytosine sensitizes B16(F10) melanoma cells to
      radiation damage when they are transfected with cytosine deaminase gene (CD). The
      greatest enhancement of radiation cytotoxicity was observed when B16(F10)/CD
      cells were incubated in medium with 500 microM 5-fluorocytosine for 3 hours, with
      incubation starting 1 hour after irradiation. 5-Fluorocytosine did not change
      radiosensitivity of parental, nontransfected cells. The isoeffective dose for CD
      transfected cells treated with 5-fluorocytosine was reduced by 20% at a 2-Gy
      level of effect for nontransfected cells. We believe that the observed outcome is
      related to 5-fluorouracil generated by CD and subsequent 5-fluorouracil
      anabolites. Our results support the development of in vivo models for tumor
      radiosensitization using the CD gene/5-fluorocytosine system.

PMID- 9253515
TI  - Quantitative reverse transcriptase-polymerase chain reaction for prostate
      specific antigen mRNA.
AB  - OBJECTIVE: To develop a quantitative reverse transcriptase-polymerase chain
      reaction assay for monitoring the prostate-specific antigen (PSA) mRNA. METHODS:
      PSA mRNA is amplified, in parallel, with the mRNA of beta-actin, a housekeeping
      gene. The ratio of the amplification products obtained reflects the relative
      amount of PSA mRNA with respect to actin mRNA. During PCR, digoxigenin-dUTP is
      incorporated in the amplified sequences. The PCR products are analyzed separately
      by time-resolved immunofluorometric hybridization assays, using specific probes
      immobilized in microtiter wells. The hybrids are reacted with alkaline
      phosphatase-labeled anti-digoxigenin antibody. The phosphate ester of
      fluorosalicylate is used as a substrate. The fluorosalicylate produced forms a
      fluorescent complex with Tb(3+)-EDTA which is measured by time-resolved
      fluorometry. RESULTS: The hybridization assays for both PSA and actin
      amplification products show linearity in the range of 1.4-110 pmol/L. The
      exponential phase of PCR amplification extends up to 200,000 and 100,000 PSA and
      actin cDNA molecules, respectively. We prepared mixtures containing various
      numbers of LNCaP cells in one million cells that do not express PSA and used them
      as samples in the proposed assay. The ratio of the fluorescence values obtained
      after analysis of PSA and actin amplification products is linearly related to the
      number of LNCaP cells in the range of 20 to 3000 cells. Reproducibility studies
      demonstrate %CVs for the fluorescence ratios of 14.7, 11.8, and 12.2 when samples
      containing 150, 300 and 1600 LNCaP cells were analyzed (n = 4). CONCLUSIONS: A
      quantitative analytical methodology is provided for monitoring PSA mRNA. The
      assay is expected to be beneficial in the study of prostate cancer spread.

PMID- 9253516
TI  - Determination of silicon in serum and tissue by electrothermal atomic absorption
      spectrometry.
AB  - OBJECTIVES: To employ an electrothermal atomic absorption spectrometry (ETAAS)
      method with chemical modifiers for the determination of silicon (Si) in serum and
      tissues. METHODS: Si was measured in serum of chronic hemodialysis patients, and
      in fibrous breast capsule tissues following silicone-gel implant removal. Tissue
      was dried, and digested with concentrated nitric acid prior to analysis. A
      chemical modifier, which included lanthanum oxide and ammonium phosphate, was
      used to dilute the serum, and digested tissue samples (1:4) before atomization.
      Si was determined at 251.6 nm in a graphite fumace using an atomic absorption
      spectrophotometer. RESULTS: The method was linear (to 1000 micrograms/L), and
      precise (CV 5.9% at 281 micrograms/L and 8.4% at 73 micrograms/L). Recovery of Si
      in spiked serum and breast tissue samples was between 97-104%. Reference values
      for women on a normal diet and no exposure to silicone implants gave serum Si to
      30 to 209 micrograms/L (n = 60), and breast tissue levels of 0.25 to 2.4
      micrograms/g dry wt (n = 48). Si in breast capsule from women exposed to silicone
      breast implants varied from 29 to 496 micrograms/g dry wt (n = 10). Serum Si in
      hemodialysis patients (n = 53) ranged from 900 to 3300 micrograms/L. CONCLUSIONS:
      We conclude that our chemically modified ETAAS method is suitable for Si
      determination in normal and elevated human serum and tissue specimens.

PMID- 9253517
TI  - Apolipoprotein E genotyping in patients with neurodegenerative diseases.
AB  - OBJECTIVES: There is a growing demand to perform apolipoprotein E (Apo-E)
      genotyping on neuropathologic archive material. Due to the extremely long
      fixation time, this material is unsuitable for routinely used Apo-E genotyping
      methods. We present an investigation into the applicability of a new method.
      DESIGN AND METHODS: An Apo-E genotyping method was tested for use on formalin
      fixed paraffin-embedded brain tissue, using semi-nested PCR followed by
      hybridization with biotin-labeled allele-specific oligonucleotides, and
      chemiluminescent detection. The method was applied to 88 archive samples of
      different neurologic disorders. RESULTS: With this technique 76% (67/88) of the
      samples could be genotyped. The crucial step is the semi-nested PCR. All the
      samples from which a PCR product could be obtained, the Apo-E gene could be
      genotyped without interpretation problems. Seventy-six percent of the samples
      that could not be genotyped, were fixed in unbuffered formalin. CONCLUSIONS: This
      technique offers a good Apo-E genotyping method applicable on neuropathological
      archive material in order to support in retrospect clinical studies.

PMID- 9253518
TI  - Mutations in cholesteryl ester transfer protein and hepatic lipase in a North
      American population.
AB  - OBJECTIVE: To examine a North American population sample with increased HDL
      cholesterol for mutations in the genes coding for cholesteryl ester transfer
      protein (CETP) and hepatic lipase (HL). DESIGN AND METHODS: Seventy individuals
      with increased HDL cholesterol at the time of initial presentation to the Lipid
      Clinic (males > 1.7 mmol/L, females > 1.8 mmol/L) were examined by polymerase
      chain reaction-restriction fragment length polymorphism (PCR/RFLP) analysis for
      known mutations in CETP intron 14 and exon 15 and HL exons 6 and 8. RESULTS: CETP
      intron 14 mutation frequency 0.7%, CETP exon 15 A1503G 0%, HL exon 6 C873T 2.1%,
      HL exon 8 C1221T 0%. An unusual mutation in CETP exon 15 G1533A was found at a
      frequency of 3.5%. The sequence of this mutation was determined to be a G to A
      change at bp 1533 resulting in a predicted amino acid change of arginine to
      glutamine at position 451. CONCLUSIONS: Known mutations in CETP were much less
      prevalent in this North American population than in the Japanese populations that
      have been previously reported. HL mutations, described previously in only 6
      families worldwide, appear to be more prevalent than previously recognized. CETP
      G1533A, reported only once previously is prevalent in this population at a
      surprisingly high frequency. The functional significance of this mutation is
      unknown.

PMID- 9253519
TI  - Effect of decreased plasma low-density lipoprotein levels on adrenal and
      testicular function in man.
AB  - OBJECTIVE: The study assessed whether serum LDL cholesterol levels affect adrenal
      and Leydig cell function in man. DESIGN AND METHODS: A 24-h continuous ACTH
      infusion was performed in 15 consecutive chronically ill patients. Serum cortisol
      and DHEA-s were measured at baseline and at 3, 6, 12, 20, and 24 h during the
      infusion. Fasting serum lipoprotein levels including LDL cholesterol, HDL
      cholesterol as well as FSH, LH, total and free testosterone concentrations were
      also measured on the baseline morning samples prior to the infusion. RESULTS: The
      initial 3 and 6 h percent rise in cortisol values during 24 h ACTH infusion were
      significantly diminished in patients with LDL-C values < 1.55 mmol/L as compared
      with patients with higher LDL-C levels (127 +/- 17% (SE) vs. 199 +/- 31% (SE); p
      < 0.02 and 115 +/- 17% vs. 213 +/- 32%; p < 0.02. However, the 24-h areas of
      cortisol under the curve were comparable in the 2 groups. Basal and ACTH
      stimulated DHEA-s levels and percent increases tended to be lower in the low LDL
      C group but the differences were not statistically significant. The mean total
      testosterone was lower in the low LDL-C group (5.30 +/- 1.78 vs. 15.60 +/- 1.95
      nmol/L; p < 0.0005). Free testosterone levels were also lower in the low LDL-C
      group (0.03 +/- 0.009 nmol/L vs. 0.08 +/- 0.01 nmol/L; p < 0.001). Five of six
      patients with low LDL-cholesterol had low testosterone values, but variable LH
      levels. CONCLUSIONS: Our results suggest that severe acquired LDL cholesterol
      insufficiency impairs slightly the initial glucocorticoid response to ACTH
      stimulation but not the overall cortisol production during sustained ACTH
      stimulation. It also may contribute to the reduction in testosterone seen in
      chronically ill patients.

PMID- 9253521
TI  - Rapid diagnosis of beta thalassemia mutations in Mediterraneans by PCR and
      restriction analysis of natural or created sites.

PMID- 9253520
TI  - BRCA1 tumor suppressor gene product shares immunoreactive epitopes with a protein
      present in seminal plasma.
AB  - OBJECTIVES: To develop immunofluorometric procedures for measuring BRCA1 protein
      in various biological fluids and tissue extracts. DESIGN AND METHODS: Five
      commercially available monoclonal and polyclonal antibodies against BRCA1 were
      evaluated for developing competitive and non-competitive immunofluorometric
      procedures for BRCA1. Biotinylated and nonbiotinylated peptides were used to
      assess the specificity of the antibodies for blocking experiments and for the
      competitive immunoassay. Extensive studies to exclude cross-reactivity and non
      specific effects in the non-competitive immunoassay were undertaken. Seminal
      plasmas as well as breast tumor extracts, amniotic fluids and cerebrospinal
      fluids were analyzed. RESULTS: We designed novel methods for measuring BRCA1
      immunoreactivity. One configuration based on the "sandwich-type" immunoassay
      principle was used for further studies. We discovered that seminal plasma
      contains an immunoreactive protein which appears to possess the D-20
      (aminoterminal) and C-20 (carboxyterminal) epitopes of BRCA1. Molecular weight
      identification using gel filtration chromatography has shown that the
      immunoreactive species has a molecular weight between 660 and 160 KDa.
      CONCLUSIONS: We identified for the first time a protein in seminal plasma that
      shares immunoreactive epitopes with the BRCA1 tumor suppressor protein. We are
      currently purifying this protein in order to examine if it is homologous or
      identical to BRCA1.

PMID- 9253522
TI  - Stoichiometric measurement of DNA damage caused by 8-methoxy-psoralen and UVA.

PMID- 9253523
TI  - Is it time to measure Lp(a) as part of coronary heart disease risk assessment?
AB  - Is Lp(a) culpable in atherosclerosis? This is a question for scientists. Lp(a)
      fulfills two of Koch's four criteria for causation for CHD. However, the actual
      mechanism by which Lp(a) promotes atherosclerosis remains unproven. Should we
      investigate Lp(a) as part of assessment of CHD risk? There are some reasons that
      favour measuring plasma Lp(a) in selected patients. First, a high Lp(a) can exist
      without physical or historical evidence. Second, the measurement of Lp(a) might
      affect diagnosis, treatment and/or prognosis. However, presently there is no
      standard assay for Lp(a) and there is no evidence for benefit of treatment
      elevated Lp(a). Furthermore, there is no current evidence that knowledge of a
      patient's Lp(a) status would affect management of other aspects of a patient's
      CHD risk. Lp(a) can be considered to be a non-modifiable potential CHD risk
      factor, as are family history and gender. If Lp(a) is to be measured, it must be
      done so using a validated, reliable and commonly used assay. Measuring Lp(a)
      could be reserved for subjects in whom there is equivocation over how
      aggressively to treat the traditional CHD risk factors, such as elevated plasma
      LDL cholesterol. If Lp(a) were found to be high in such a subject, the modifiable
      CHD risk factors should be addressed more aggressively. However, the medical
      community awaits the results of prospective studies addressing this particular
      issue.

PMID- 9253524
TI  - Proposed definitive methods for measurement of plasma testosterone and 17 alpha
      hydroxyprogesterone.

PMID- 9253525
TI  - Left unilateral ECT: still a viable option?

PMID- 9253526
TI  - ECT in patients with major depressive disorder and low cardiac output.
AB  - Electroconvulsive therapy (ECT) in patients with impaired cardiac output may be
      associated with significant cardiovascular morbidity and mortality because of its
      hemodynamic effects. Many clinicians are reluctant to treat these patients with
      ECT because of the high risk associated with the treatment. In this report, we
      present a clinically appropriate protocol for ECT treatment of patients with
      impaired cardiac output and major depressive disorder. Three patients, ages 59-78
      years, with resistant major depression and impaired cardiac output (ejection
      fraction 20-25%), were successfully treated with ECT according to this protocol.

PMID- 9253527
TI  - ECT for the treatment of intractable mania in two prepubertal male children.
AB  - We provide case reports of the successful use of electroconvulsive therapy (ECT)
      for intractable mania in two prepubertal male children. Both children responded
      well to ECT without significant complications. The report focuses in particular
      on the procedure and technique of doing ECT in this patient population.

PMID- 9253528
TI  - Bridging the skull: electroconvulsive therapy (ECT) and repetitive transcranial
      magnetic stimulation (rTMS) in psychiatry.
AB  - A brief account of repetitive transcranial magnetic stimulation (rTMS) with
      reference to electroconvulsive therapy (ECT) is given, identifying similarities
      and dissimilarities, and discussing their potential therapeutic roles. The
      insulating properties of the skull prevent specific, noninvasive stimulation of
      particular brain regions by direct electrical means. ECT allows electrical
      stimulation of the cortex, but its concomitant seizures and distributed
      electrical currents can have adverse effects on patients. By contrast, magnetic
      fields pass almost without attenuation through the skull, and can induce
      secondary electrical currents in localized areas of the brain. Subconvulsive rTMS
      does not require seizure or general anesthetic, and does not affect memory.
      Recent studies suggest that rTMS has therapeutic potential for mood disorders,
      for which ECT is well established. rTMS is a new technology with the potential to
      treat some mental disorders currently treated with ECT, with fewer side effects.
      ECT will almost certainly remain the treatment of choice in some situations, but
      ECT and rTMS may be alternatives for other patients. It is possible that rTMS
      will become established in some areas where ECT is not used. Further research
      will define these roles and evaluate the utility of rTMS.

PMID- 9253529
TI  - Curare: a preventive of traumatic complications in convulsive shock therapy
      (including a preliminary report on a synthetic curare-like drug). 1940.

PMID- 9253530
TI  - ECT for the treatment of Huntington's disease: a case study.
AB  - We report a 56-year-old man with Huntington's disease whose chorea substantially
      improved after treatment with electroconvulsive therapy (ECT). ECT should be
      considered for medically refractory cases of movement disorders, especially those
      with severe disability.

PMID- 9253531
TI  - Combination midazolam and droperidol for severe post-ECT agitation.

PMID- 9253532
TI  - Delirium in a 75-year-old woman receiving ECT and levodopa.

PMID- 9253533
TI  - Mirtazapine and ECT combination therapy.

PMID- 9253534
TI  - Lipids, lipoproteins, obesity and the cardiovascular risk, what is new and what
      has been left aside.

PMID- 9253535
TI  - Obesity and cardiovascular disease: is body structure a factor?
AB  - Obesity is associated with increased cardiovascular morbidity and mortality.
      Individuals who predominantly store fat abdominally (particularly in the visceral
      area), more often present with an atherogenic lipid profile and are more
      frequently characterized by hemostatic, metabolic and anatomical abnormalities
      compatible with insulin resistance and increased atherothrombotic risk. Weight
      loss improves many of the cardiovascular risk factors associated with abdominal
      obesity.

PMID- 9253536
TI  - Familial aggregation of obesity, candidate genes and quantitative trait loci.
AB  - This brief review covers the findings reported in 1996 and in the first 2 months
      of 1997 on the genetic epidemiology and the molecular markers of human obesity.
      Although relatively little new evidence has been published on the heritability
      and other genetic epidemiology characteristics of obesity and fat topography,
      more has been reported on candidate genes, positional candidate genes and
      quantitative trait loci. Two recent genome-wide scans have revealed that several
      molecular markers on different chromosomes were linked to obesity-related
      phenotypes. Little support for a role for specific candidate genes can be found
      at this time. A large number of rodent quantitative trait loci have been
      uncovered so far but they have not yet been systematically tested in human
      populations.

PMID- 9253537
TI  - Peroxisome proliferator-activated receptor gamma and the control of adipogenesis.
AB  - The adipose cell is now known to play a complex role in energy homeostasis,
      storing energy and signaling to other tissues concerning the state of energy
      balance. The past several years have seen an explosive increase in our knowledge
      of the transcriptional basis of adipocyte differentiation. This review describes
      the role of peroxisome proliferator-activated receptor gamma in this process, and
      describes how other transcription factors may affect adipogenesis by modulating
      the amount or activity of peroxisome proliferator-activated receptor gamma.
      Furthermore, peroxisome proliferator-activated receptor gamma and other
      adipogenic transcription factors provide a focus for beginning to understand how
      various hormones and metabolites influence the development of this tissue in
      vivo.

PMID- 9253538
TI  - High density lipoprotein and coronary heart disease: insights from mutations
      leading to low high density lipoprotein.
AB  - Hypoalphalipoproteinemia can result from defects in the genes encoding
      apolipoprotein A-I, the major protein component of HDL, or enzymes that are
      critical for the formation/maturation of mature HDL. Recent information
      contradicts earlier findings, suggesting that most of the affected subjects are
      at increased risk of developing coronary heart disease, independent of the
      mutated gene. A possible exception is represented by mutations in the
      apolipoprotein A-I gene leading to structural variants, that might even exert a
      protective effect against atherosclerosis.

PMID- 9253539
TI  - Pharmacology of apolipoprotein A-I.
AB  - The role of HDL and its main protein component the apolipoprotein A-I as being
      antiatherogenic is well established. Experimental data give support for the
      involvement of at least three different types of mechanism: (1) the reverse
      cholesterol transport, (2) anti-inflammatory mechanisms and (3) antithrombotic
      mechanisms. Depending upon the stage and type of atherosclerosis, different
      mechanisms may be more or less important. Knowledge of pharmacology of
      apolipoprotein A-I has strongly increased during past years and clinical studies
      have started with infusions of apolipoprotein A-I phospholipid complexes.

PMID- 9253540
TI  - The menopause and lipid metabolism: strategies for cardiovascular disease
      prevention.
AB  - The menopause and its biology are as yet still incompletely understood. Very
      little is known about biological and molecular changes in cardiovascular target
      tissues and organs after menopause. Experimental and clinical evidence indicate
      that prevention of cardiovascular disease by estrogens is aimed both at the
      correction of risk factors and at the direct control of vessel structure and
      function. The effects of progestogens on these processes are still debated. Few
      other medical interventions have as great a potential for affecting morbidity and
      mortality as does hormone replacement therapy in postmenopausal women. Hormone
      replacement therapy has produced effects on health risk, some are reduced, some
      are raised, while some remain uncertain, suggesting that further testing through
      specific clinical trials are required before confident recommendations can be
      made about the full range of benefits and risks. Lipid lowering therapy may be an
      acceptable alternative for postmenopausal women at risk for cardiovascular
      disease.

PMID- 9253541
TI  - Lipoprotein alterations and atherosclerosis in the elderly.
AB  - Lipoproteins play a key role in the pathogenesis of atherosclerotic diseases.
      With increasing age, modifications in the metabolism, distribution and correlates
      of lipoprotein lipids have been described. Age associated changes in lipoproteins
      are determined by several genetic and environmental factors, but in elderly
      populations, an important role is also played by the presence of comorbid
      diseases and poor health. In older populations, the ability of lipoprotein levels
      to predict cardiovascular risk is controversial. When lipoprotein levels are
      measured at old age, secondary changes in total and high density lipoprotein
      cholesterol levels may lead to misclassification and to underestimation of
      associations. When analyzing associations in older populations, it is therefore
      important to consider measures of disease burden and comorbidity. When these
      caveats are taken into account, evidence from observational studies in older
      persons confirms the association between lipoprotein lipids, cardiovascular and
      cerebrovascular disease. Among older patients with cardiovascular disease,
      intervention trials have demonstrated that lipid lowering drugs can significantly
      reduce total and coronary heart disease mortality. Unequivocal evidence that
      lipid-lowering drugs are beneficial in old and very old persons without pre
      existing cardiovascular disease is still lacking. Results from primary and
      secondary intervention trials in older men and women are needed to provide
      conclusive guidelines.

PMID- 9253542
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 9253543
TI  - Nutrition and therapeutics.

PMID- 9253544
TI  - Genetics and molecular biology.

PMID- 9253545
TI  - Lipid metabolism.

PMID- 9253546
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 9253547
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 9253548
TI  - Therapy and clinical trials.

PMID- 9253549
TI  - Relation of maternal ethnicity to infant birthweight in east London, England.
AB  - OBJECTIVE: We sought to determine whether black race is a risk factor for very
      low birthweight in a developed country other than the United States. DESIGN: A
      cross-sectional study was performed. SETTING: We analyzed a dataset of 1987-1990
      birth records from three hospitals in East London, England. PARTICIPANTS: All
      live born African (N = 3,495), West Indian (N = 3,471), and European white (N =
      20,313) singleton infants born to East London residents. MAIN OUTCOME MEASURES:
      For each ethnic group, we calculated the proportion of very low birthweight (<
      1500g) and moderately low birthweight (1500-2499g) infants. RESULTS: The very low
      birthweight rate was 2.9% for infants of West Indian descent and 2.2% for infants
      of African descent vs. 1.3% for European whites; odds ratio (95% confidence
      interval) = 2.1(1.7-2.8) and 1.8(1.2-3.1), respectively. West Indian and white
      mothers were similar in terms of age, social support, and prenatal care. African
      mothers were older and had less social support. The West Indian:white and
      African:white differentials in very low birthweight rates persisted among low
      risk mothers; odds ratio (95% confidence interval) = 2.7(1.7-4.0) and 2.3(1.5
      3.6), respectively. CONCLUSIONS: We conclude that black race is a risk factor for
      very low birthweight in the United Kingdom.

PMID- 9253550
TI  - Preeclampsia and neonatal outcomes in chronic hypertension: comparison between
      white and black women.
AB  - We compared the incidence of preeclampsia and neonatal outcomes in 208 white
      (born in Canada) and 74 black (born in Haiti) women with mild chronic
      hypertension. Controls included 17,677 white and 2,400 black normotensive women
      delivered in the same center between 1987 and 1991. Superimposed preeclampsia
      (32.4% vs 14.9%; p < 0.01), perinatal mortality (9.5% vs 2.9%; p < 0.05) and
      prematurity (32.4% vs 19.7%; p < 0.05) were more frequent in black than in white
      women with chronic hypertension. Within both races, chronic hypertensive women
      with superimposed preeclampsia demonstrated higher rates of perinatal mortality
      and morbidity than controls. White chronic hypertensive women without
      preeclampsia and controls had similar rates of perinatal mortality as compared to
      black study participants and controls (2.3% vs 1.4%), small-for-gestational-age
      newborns (10.7% vs 7.8%) and prematurity (12.4% vs 15.3%). Compared to black
      controls, black chronic hypertensive women without preeclampsia had higher rates
      of perinatal mortality (1.2% vs 8.0%; p < 0.001) and prematurity (9.0% vs 18.0%;
      p < 0.05). These data provide evidence of ethnic differences in perinatal
      outcomes in chronic hypertensive women that are not explained only by
      superimposed preeclampsia.

PMID- 9253551
TI  - Middle digestive cancers in Texas Hispanics: a New World syndrome?
AB  - To test the hypothesis that middle digestive cancers in Texas Hispanics follow
      the patterns predicted by the New World Syndrome (1984), cancer incidence rates
      and relative risks for middle digestive cancers were estimated for 1944-1992. The
      relative risk for all middle digestive cancers is significantly elevated in Texas
      Hispanics compared with Anglos, and this risk has increased over time. Elevated
      risks of these cancers in Texas Hispanics have been explained as resulting from
      the evolutionary history of Native Americans (American Indians), their genetic
      relation to Texas Hispanics, and a changing diet and lifestyle. Recent Texas
      cancer incidence data add further support to the hypothesis. Other current
      disease prevalence data in Texas Hispanics, percent of the population which is
      diabetic and percent which is overweight, are also consistent with the New World
      Syndrome. Expected patterns of disease in males vs females are also confirmed.
      Factors that do not support the New World Syndrome hypothesis and can be examined
      by future studies are described. This is the first report since the original
      describing and updating patterns of middle digestive cancers in Texas Hispanics
      as resulting from the New World Syndrome. Application of these findings to
      contemporary medical practice and to cancer prevention are reviewed.

PMID- 9253552
TI  - Is there a difference in hypertensive claim rates among Medicaid recipients?
AB  - The purpose of this study was to determine whether there are racial differences
      in the rates of prevalence and new claims to Medicaid for hypertension treatment
      in a population of uniformly low economic status--i.e., Georgia Medicaid
      recipients. Age-specific and age-adjusted prevalence rates of hypertension in
      1991 and the first 1991 claim rates by race and gender were calculated. Gender
      specific black-to-white risk ratios, using the Mantel-Haenszel pooled point
      estimate (RMH) and the corresponding test-based 95 percent confidence interval
      (CI) were also calculated. African-American females were more likely than African
      American males, or whites of either sex to have hypertension diagnoses. For newly
      claimed cases, the gender-specific black-to-white risk ratios were significant in
      malignant hypertension for both females (RMH = 1.9, 95 percent CI 1.4-2.5) and
      males (RMH = 2.0, 95 percent CI 1.2-3.7) and in unspecified hypertension for
      females (RMH = 1.5, 95 percent CI 1.4-1.6), but were less significant in
      unspecified hypertension for males, and in benign hypertension for both sexes.
      Using Medicaid data may have caused underestimation of the prevalence and
      incidence of hypertension among Medicaid recipients; however, significant racial
      differences in the "occurrence" of hypertension still existed among them. Factors
      other than the household income status may be responsible for much of the excess
      risk of hypertension in the black Medicaid population.

PMID- 9253553
TI  - Incidence of spontaneous subarachnoid hemorrhage among Hispanics and non-Hispanic
      whites in New Mexico.
AB  - BACKGROUND AND PURPOSE: There are differences in cerebrovascular disease
      incidence between racial and ethnic groups. Little is known about cerebrovascular
      disease among Hispanics living in the southwestern United States as compared to
      non-Hispanic whites. This is the first study which measures and compares the
      incidence of spontaneous subarachnoid hemorrhage (SAH) among Hispanics and non
      Hispanic whites living in Bernalillo County, New Mexico. This information may
      help reduce the risk and incidence of SAH. METHODS: Medical records of all
      possible cases of spontaneous SAH occurring during a two-year period (January 1,
      1993 to December 31, 1994) among residents of Bernalillo County, New Mexico, were
      reviewed in all local hospitals. Hospital records were identified by ICD-9-CM
      codes. Medical examiner records were also reviewed for additional SAH cases
      occurring during the same time period. The 1990 U.S. census provided the
      population base. RESULTS: There were 22 spontaneous SAHs among 267,965 non
      Hispanic whites and 25 spontaneous SAHs among 178,310 Hispanics. Incidence of SAH
      increased with age in both groups. The age- and sex-adjusted total annual
      incidence of SAH per 100,000 people was 3.73 among non-Hispanic whites and 9.19
      among Hispanics (relative risk for Hispanics 2.46, 95% confidence interval 1.37
      4.43, P = 0.003). The incidence rates among men and women were not significantly
      different in either ethnic group. CONCLUSIONS: The incidence of SAH among
      Hispanic residents of Bernalillo County, New Mexico, is approximately two and a
      half times higher than that among non-Hispanic whites. This suggests a higher
      prevalence or a greater tendency to rupture of berry aneurysms among Hispanics as
      compared to non-Hispanic whites. The reasons for this difference require further
      investigation.

PMID- 9253554
TI  - Skin tone, hostility, and blood pressure in young normotensive African Americans.
AB  - Several studies have found a positive relationship between darkness of skin tone
      and blood pressure in African Americans. This has raised speculation about the
      relative contributions of genetic and/or psychosocial factors in the mediation of
      this relationship. Using a laboratory stress protocol, we performed
      cardiovascular reactivity testing with 42 male and 40 female African-American
      college students after pre-testing them on measures of hostility using four
      psychometric scales derived from the Minnesota Multiphasic Personality Inventory
      (MMPI). Skin tone measures were obtained with a reflectance spectrophotometer. In
      the combined sample of males and females, we found a weak but statistically
      significant positive relationship between darker skin tone and systolic blood
      pressure (p = 0.03). However, males were significantly darker than females (p =
      .005) suggesting that the skin tone and blood pressure relationship is an
      artifact of gender. No differences in patterns of cardiovascular habituation or
      levels of hostility were found between dark and light subjects. Discussion of
      these results focuses on the weak statistical relationship found in this and
      other studies and the specificity of previous findings based on educational and
      socioeconomic factors.

PMID- 9253555
TI  - The development and evaluation of the hypertension temporal orientation (HTO)
      scale.
AB  - Temporal orientation is a multidimensional concept that describes the perception
      of time among individuals. Time perception is structured by life experiences and
      can vary depending upon the particular context involved. Whether a person is past
      , present- or future-oriented has been shown to influence his/her approach and
      reaction to health situations. Because the management of hypertension is based on
      achieving some future health state, hypertension provides a context in which an
      individual's time perspective may be particularly influential. One purpose of
      this study was to develop and evaluate a scale to measure temporal orientation
      that was specific to hypertension, namely the hypertension temporal orientation
      (HTO) scale. Data were collected via telephone interviews with 300 people who had
      been diagnosed by a physician as having hypertension. Principal components factor
      analysis revealed three dimensions of hypertension temporal orientation: (1) a
      nonexperiential domain; (2) an experiential disease domain; and (3) an
      experiential treatment domain with coefficient alpha estimates of 0.76, 0.66, and
      0.63, respectively. The HTO scale was significantly discriminant of African
      Americans and whites on the experiential treatment domain whereby African
      Americans were more present-oriented regarding the daily management (or
      treatment) of hypertension as compared to whites. Additional evidence for the
      validity of the HTO scale was found with temporal orientation group comparisons
      on health perceptions. The findings provide early support for the reliability and
      validity of the HTO scale for measuring temporal orientation among people with
      hypertension.

PMID- 9253556
TI  - The influence of birthplace on mortality among Hispanic residents of New York
      City.
AB  - To determine the mortality experience of Hispanic residents of New York City and
      the influence of birthplace on their mortality rates, NYC Department of Health
      mortality records for 1988 to 1992 were linked for analysis with 1990 United
      States census data for New York City. Age-specific death rates for all Hispanics
      were compared by birthplace with those of non-Hispanic whites. Age-adjusted death
      rates were also compared. Overall, Hispanics had death rates lower than non
      Hispanic blacks, and death rates similar to those of non-Hispanic whites.
      Hispanics had higher rates of death from HIV-infection, diabetes,
      stroke/hypertensive disease, cirrhosis and homicide, and fewer deaths from cancer
      and coronary heart disease than did non-Hispanic whites. Moreover, there were
      substantial differences in mortality between Hispanic subgroups categorized by
      birthplace. Migrants from Puerto Rico had the highest, and those from Central and
      South America the lowest mortality rates. United States-born Hispanics, although
      younger, had age-adjusted mortality rates higher than New York City non-Hispanic
      whites. In summary, the mortality of Hispanics generally approximated that of non
      Hispanic whites, and was lower than that of non-Hispanic blacks. However,
      stratification of Hispanics by birthplace revealed substantial variation within
      the Hispanic population of New York City.

PMID- 9253557
TI  - Health status of diabetic persons in an Asian-Pacific population: evidence from
      Guam.
AB  - OBJECTIVE: The goal of this study was to document the sociodemographic, physical,
      and psychosocial health characteristics of self-reported diabetic Asian-Pacific
      Americans in Guam. METHODS: Data from Guam's 1991 Behavioral Risk Factor Survey
      were analyzed using analysis of variance. RESULTS: Diabetic men are significantly
      more likely than nondiabetic men to be Chamorro, not to have graduated from high
      school, to be unemployed, and to be impoverished. Diabetic women are also
      significantly more likely than nondiabetic women to be impoverished. Hypertension
      is more prevalent among diabetic men and women than among nondiabetic persons.
      Diabetic men are at greater risk than nondiabetic men for heart attack, and are
      significantly more likely to assess their physical health as poor. Diabetic women
      are more likely than nondiabetic women to suffer strokes. CONCLUSIONS: The
      results of this study indicate significant differences in the health status of
      diabetic and nondiabetic Asian-Pacific persons in Guam and extends our
      understanding of the health characteristics and service needs of this rapidly
      growing and under-studied population.

PMID- 9253558
TI  - Can hypertension be prevented? Applications of risk modifications in black
      populations: U.S. populations.

PMID- 9253559
TI  - Just how benign is renal dopamine?

PMID- 9253560
TI  - Transoesophageal echocardiography in critically ill patients. A comprehensive
      approach.

PMID- 9253561
TI  - The minimum alveolar concentration of sevoflurane in rats.
AB  - There are only limited data on sevoflurane minimum alveolar concentration (MAC)
      in rats. This study was designed to determine the minimum alveolar concentration
      value for sevoflurane in younger and older rats. Minimum alveolar concentration
      determination was performed in spontaneously breathing animals, 9-week-old rats
      (younger, n = 8) and more than 13-month-old rats (older, n = 8). Rats were
      instrumented with a silastic catheter in the abdominal aorta via the femoral
      artery to allow for arterial blood gas sampling. Subsequently, minimum alveolar
      concentration for sevoflurane was determined in 40 younger and 38 older rats.
      Minimum alveolar concentration for sevoflurane in younger rats was significantly
      higher than in the older rats (2.68 +/- 0.19 vs. 2.29 +/- 0.19, P < 0.001).
      Subgroup analysis indicated that minimum alveolar concentration for sevoflurane
      was not affected by the presence of an arterial catheter in the abdominal aorta
      (younger, 2.75 +/- 0.08 vs. 2.67 +/- 0.21; older, 2.23 +/- 0.19 vs. 2.30 +/-
      0.18). Minimum alveolar concentration is profoundly affected by the age of the
      animal, but not by limited instrumentation.

PMID- 9253562
TI  - Ondansetron, droperidol and their combination for the prevention of post
      operative vomiting in children.
AB  - In this study the antiemetic effects of droperidol, ondansetron and their
      combination were evaluated in 160 ASA Grade I and II children undergoing surgery
      for strabismus, who were randomly assigned to one of four groups: Group D
      received droperidol 75 micrograms kg-1, group O ondansetron 0.1 mg kg-1, group
      D+O received both droperidol 75 micrograms kg-1 and ondansetron 0.1 mg kg-1, and
      group N NaCl as placebo. Emesis within the first 24 h occurred in 95.0% of the
      children with placebo medication, compared with 32.5% (D), 40.0% (O) and 45.0%
      (D+O) in the groups with antiemetic prophylaxis. The differences between group N
      and all other groups were significant (P < 0.001). However, there were no
      statistically significant differences between the groups D, O and D+O. It is
      concluded that droperidol (75 micrograms kg-1) and ondansetron (0.1 mg kg-1) both
      significantly reduce PONV in children undergoing surgery for strabismus. Neither
      ondansetron, nor the combination D+O were superior to droperidol alone.

PMID- 9253563
TI  - Prevention of patient bacterial contamination of anaesthesia-circle-systems: a
      clinical study of the contamination risk and performance of different heat and
      moisture exchangers with electret filter (HMEF).
AB  - The microbiological contamination of 250 breathing system tubes after use in
      anaesthesia circle systems with reduced fresh gas flow was investigated. The
      lungs of 50 patients were ventilated without any filtering device between the
      endotracheal tube and the Y-piece. A total of 51, 49 and 100 patients,
      respectively, were given different types of heat and moisture exchanger with
      electret filters (HMEF). With no filtering device the tubing system was
      contaminated by microorganisms originating from the patient's tracheal secretion
      in 13% of the patients. In contrast, no bacterial migration into the tubing
      system was detected when any of the investigated HMEF-devices were used. We
      therefore conclude that heat and moisture exchangers with electret filters
      prevent contamination of the anaesthesia breathing system with microorganisms
      from the patients airways.

PMID- 9253564
TI  - Transition to post-operative epidural or patient-controlled intravenous analgesia
      following total intravenous anaesthesia with remifentanil and propofol for
      abdominal surgery.
AB  - Remifentanil is an ultrashort acting mu opioid, well suited to total intravenous
      (i.v.) anaesthesia. Pain immediately following emergence from anaesthesia is a
      potential problem because of the rapid offset. This study investigated the
      transition from remifentanil/propofol total intravenous anaesthesia to post
      operative analgesia with epidural or patient controlled analgesia morphine in 22
      patients undergoing major abdominal surgery. A remifentanil post-operative
      infusion initiated during emergence was titrated in the recovery room for 30 min,
      at which time 14% of patients had a pain score of 2 and 86% had pain scores of 0
      or 1 (0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severe pain), at a mean
      infusion rate of 0.086 microgram kg-1 min-1. A smooth transition was then made to
      either epidural analgesia or patient controlled analgesia with morphine; pain
      scores were not significantly changed during the transition. Nausea occurred in
      16 of the 22 patients, but only following administration of morphine. Epidural
      analgesia produced significantly lower pain scores on the surgical ward compared
      with patient controlled analgesia.

PMID- 9253565
TI  - Comparison between the Ovassapian intubating airway and the Berman intubating
      airway in fibreoptic intubation.
AB  - The most common indication for employing the fibreoptic technique for intubation
      is when a difficult intubation is anticipated. It may also be used when
      intubation unexpectedly proves difficult with a rigid laryngoscope in
      anaesthetized patients. However, failures with orotracheal fibreoptic intubation
      have been reported in up to 9.5% of cases, although only two possible equipment
      related causes of intubation difficulties have been identified. The Berman
      intubating airway and the Ovassapian intubation airway in fibreoptic orotracheal
      intubation have been compared in 65 patients. The study was randomized and for
      fibreoptic endoscopy each patient served as his or her own control. The results
      indicate that both airways can be used for orotracheal fibreoptic intubation in
      anaesthetized patients. The Berman airway offers easier visualization of the
      vocal cords than the Ovassapian airway, provided that the Berman airway is of an
      adequate size and positioned in the midline. Upon impingement of the intubation
      tube, completing the tracheal intubation is more difficult with the Berman airway
      than the Ovassapian airway.

PMID- 9253566
TI  - Effect of intra-operative mechanical ventilation using 50% inspired oxygen on
      pulmonary oxygenation.
AB  - Forty-three ASA Grade I patients scheduled for elective abdominal surgery
      received at random either 25% or 50% inspired oxygen for intra-operative
      mechanical ventilation lasting 4-6 h. Pulse oximetry was monitored continuously.
      Venous admixture was assessed from the PaO2/FIO2 ratio and was measured twice
      intraoperatively: at the time of incision, and during surgical wound closure.
      PaO2 was measured 1 h after extubation having breathed room air for 10 min, if
      tolerated. The patients in the two groups were similar in regard to general
      characteristics, and had similar operations. Patients given oxygen 50% had
      operations that lasted longer, which made the trial more sensitive. The inspired
      oxygen did not affect pulmonary gas exchange either within each group or between
      groups under the conditions of the study. In no patient did pulse oximetry record
      an oxygen saturation below 95% intra-operatively.

PMID- 9253567
TI  - Administration of sufentanil and nitrous oxide blunts cardiovascular effects of
      desflurane but does not prevent an increase in middle cerebral artery blood flow
      velocity.
AB  - Desflurane has been reported to cause tachycardia and hypertension during
      induction of anaesthesia. The aim of this study was to determine the effects of
      desflurane on cerebral blood flow (CBF) velocity using transcranial Doppler
      ultrasonography in a setting that closely resembled usual clinical practice. In
      two groups (n = 9 in each) ASA Grade I or II patients, anaesthesia was induced
      with etomidate and vecuronium intravenously (i.v.), sufentanil (0.3 microgram kg
      1 i.v.) was added in the second group. Patients were ventilated by facemask for 2
      min before desflurane was administered in steps of 0.5 MAC min-1 until 1.5 MAC
      was reached and maintained for 7 min. Haemodynamic variables and CBF velocity in
      the middle cerebral artery (MCA) were monitored throughout the study period. In
      group 1 heart rate increased to 108 +/- 2 b.p.m. (37% increase) whereas MAP
      increased to 114 +/- 6 mmHg after administration of desflurane (33% increase).
      CBF velocity increased to 86 +/- 7 cm s-1 (69% increase). In group 2 no
      significant changes in systemic haemodynamic responses were measured after
      desflurane administration; however, CBF velocity increased to 73 +/- 5 cm s-1
      (59% increase). The results indicate that desflurane increases CBF velocity
      concurrently with induction of tachycardia and hypertension. Although sufentanil
      and N2O attenuate the systemic haemodynamic alterations caused by desflurane, the
      CBF velocity increases. These data suggest that the abrupt addition of desflurane
      may have adverse consequences in patients at risk for intracranial hypertension.

PMID- 9253568
TI  - Early assessment of transplanted liver function: lignocaine clearance test
      (MEGX).
AB  - The purpose of this study was to assess the value of lignocaine biotransformation
      into monoethylglycinexylidide (MEGX) and conventional liver function tests in the
      early post-operative period as an indicator of graft function and as a diagnostic
      tool for complications after hepatic transplantation. Monoethylglycinexylidide
      formation, plasma bilirubin, aspartate aminotransferase (ASAT), alanine
      aminotransferase (ALAT), factor V index (FVI) and prothrombin time index (PTI)
      were measured in 71 patients undergoing 80 liver transplantations respectively at
      12 (T1), 24 (T2), 48 (T3) and 72 h (T4) after liver graft revascularization.
      Patients were divided into two group according to the post-operative outcome.
      Patients with favourable outcome (n = 59) had significantly higher
      monoethylglycinexylidide synthesis, higher factor V index and prothrombin time
      index plasma concentrations, lower bilirubin, ASAT and ALAT plasma concentration
      (P < 0.0001 at T2 and T3) than those with complicated time course (n = 21).
      Monoethylglycinexylidide synthesis was the best discriminant of a favourable
      outcome, whereas bilirubin and ALAT concentrations were associated with
      complications (bilirubin for primary non function [PNF], ALAT for acute
      rejection). Thus, the combination of parameters at T2 was a very efficient
      predictor of primary non function, acute rejection and an uncomplicated time
      course.

PMID- 9253569
TI  - Cardiac output and ethanol monitoring of fluid absorption.
AB  - The purpose of this experimental study was to find out whether central
      haemodynamic activity influences the precision of the ethanol method used to
      monitor fluid absorption during endoscopic surgery. Today, the nomograms used
      together with this monitoring method indicate that increasing breath ethanol
      values reflect progressively larger absorption volumes regardless of the
      haemodynamic situation. Cardiac output was measured by ultrasound-Doppler and
      compared with the concentrations and pharmacokinetics of ethanol in the breath
      during and after 13 intravenous (i.v.) infusions of 15 mL kg-1 of irrigating
      fluid containing 1% of ethanol in nine healthy male volunteers. The results show
      that the peak ethanol concentration increases with cardiac output. This can
      probably be explained by the shorter time needed for the blood to reach and to
      return from well perfused tissues, thereby prolonging the apparent rate of
      distribution to poorly perfused tissues. It is concluded that a hyperkinetic
      circulation causes the ethanol monitoring method to indicate larger absorption
      volumes.

PMID- 9253570
TI  - Biplane transoesophageal echocardiographic detection of myocardial ischaemia in
      patients with coronary artery disease undergoing non-cardiac surgery: segmental
      wall motion vs. electrocardiography and haemodynamic performance.
AB  - Intra-operative segmental wall motion abnormalities (SWMA) detected by
      transoesophageal echocardiography (TOE) have been shown to be a sensitive
      indicator of myocardial ischaemia. To determine the incidence and characteristics
      of segmental wall motion abnormalities and to relate these changes to
      perioperative myocardial ischaemia, biplane TEE, electrocardiogram (ECG) (II+V5)
      and pulmonary capillary wedge pressure (PCWP) were continuously monitored in 62
      consecutive patients with ischaemic heart disease undergoing non-cardiac surgery.
      Short-axis view at mid-papillary level in transverse scan (T-scan) and long-axis
      in longitudinal (L-scan) two-chamber view were used for wall motion analysis. New
      segmental wall motion abnormalities were detected in 16 of 64 patients (25%)
      using biplane transoesophageal echocardiography. Monoplane transoesophageal
      echocardiography showed a sensitivity of 75% and a specificity of 100%,
      electrocardiogram two lead showed a sensitivity of 56% and a specificity of 98%,
      whereas pulmonary capillary wedge pressure had a sensitivity of 25%, and a
      specificity of 93% and pressure rate quotient (PRQ) < 1 demonstrated sensitivity
      of 19% and a specificity of 92% in the detection of myocardial ischaemia. It is
      concluded that the long-axis view of the left ventricle provides additional
      information for the detection of segmental wall motion abnormalities. Neither
      changes in haemodynamic performance nor in electrocardiography leads II and V5
      match those of transoesophageal echocardiography for the identification of
      myocardial ischaemia.

PMID- 9253571
TI  - Premedication with controlled release diclofenac sodium reduces post-operative
      pain after minor gynaecological surgery.
AB  - The effect of a single pre-operative oral dose of controlled release diclofenac
      sodium on post-operative pain after minor gynaecological surgery was
      investigated. Fifty-two women took part in a double-blind controlled study. Pain
      was assessed by visual analogue scale (VAS), a four-point verbal rating score,
      and the requirement for post-operative analgesia. Those patients who received
      diclofenac had significantly less post-operative pain than the placebo group up
      to 2 h after surgery.

PMID- 9253572
TI  - Antiseptic-impregnated central venous catheters reduce the incidence of bacterial
      colonization and associated infection in immunocompromised transplant patients.
AB  - The incidence of bacterial colonization of central venous catheters using a
      standard polyurethane catheter was compared with that using an antiseptic (silver
      sulphadiazine and chlorhexidine) impregnated catheter in a group of patients with
      thoracic organ transplantation. Colonization was reduced from 25 of 35 standard
      catheters to 10 of 44 study catheters (P < 0.002), a 68% reduction. Similarly,
      the incidence of concomitant infection, by the same organism at another site was
      reduced from 10 of 35 standard catheters to 4 of 44 study catheters (P < 0.03), a
      63% reduction.

PMID- 9253573
TI  - Epoetin alfa facilitates presurgical autologous blood donation in non-anaemic
      patients scheduled for orthopaedic or cardiovascular surgery.
AB  - Patients expected to need at least three units of blood for their elective
      cardiovascular or orthopaedic surgery, were allocated randomly to receive
      intravenous (i.v.) Epoetin alfa 600 IU kg-1 (n = 27), 300 IU kg-1 (n = 30) or
      placebo (n = 23), on days 1, 4 and 7. Provided haemoglobin > or = 11 g dL-1, one
      unit of blood was collected on days 1, 4, 7, 11 and 14. Iron supplementation was
      given throughout the study. Surgery was scheduled between days 18 and 21.
      Significantly more patients treated with Epoetin alfa (100% for 600 IU kg-1; 97%
      for 300 IU kg-1) were able to donate > or = 4 units of blood compared with
      placebo (78%) (P = 0.011 and P = 0.032). No significant differences were seen in
      total patient exposure to homologous blood (7.4%, 3.3% and 17.4%, respectively).
      Mean red cell volume donated (P = 0.005 for 600 IU kg-1; P = 0.158 for 300 IU kg
      1 both vs. placebo) and production (P < 0.001 and P = 0.012, respectively) were
      dose related. Twenty-four patients became iron deficient. No differences in the
      incidence of adverse events were seen between the groups.

PMID- 9253574
TI  - Acute haemodilution and prostaglandin E1-induced hypotension: effects on the
      coagulation-fibrinolysis system.
AB  - The effects of acute haemodilution, during prostaglandin E1 (PGE1)-induced
      hypotension, on the blood coagulation-fibrinolysis system were studied in 40
      patients undergoing hip surgery. The patients were randomly divided into four
      groups of 10 patients each; Group A (control) received no induced hypotension or
      haemodilution, group B received hypotension alone, group C received haemodilution
      alone and group D received the combination of induced hypotension and
      haemodilution. Haemodilution in groups C and D was produced by drawing
      approximately 1000 mL of blood and replacing it with the same amount of 6%
      hydroxyethyl starch. Induced hypotension in groups B and D was conducted with
      PGE1 and mean blood pressure was maintained at 55 mmHg. The mean dosage of PGE1
      was 648 micrograms in group B and 661 micrograms in group D. In the control and
      PGE1-induced hypotension groups there was no significant change in platelet count
      (PLT), prothrombin time (PT), activated partial thromoplastin time (aPTT),
      fibrinogen (FIB), antithrombin-III (AT-III) or plasminogen (PLG). Haemodilution
      alone caused significant decreases in PLT (-43%), PT (+21%), FIB (-33%), AT-III (
      21%) and PLG (-27%), and a significant increase in aPTT (+26%), whereas the
      combination of PGE1-induced hypotension did not cause any further change in these
      parameters. Serum-fibrin degradation products (FDP) significantly increased
      (+300%) and PLG significantly decreased (-30%) after surgery in all groups. It
      can be concluded that acute haemodilution to a haematocrit value of 22 +/- 2%
      causes a slight coagulopathy, which is not enhanced when combined with PGE1
      induced hypotension.

PMID- 9253577
TI  - Extracorporeal shock wave lithotripsy in a patient with complete atrioventricular
      heart block.
AB  - Extracorporeal shock wave lithotripsy using a spark gap generator is
      contraindicated in patients with complete atrioventricular heart block. A case of
      a patient with such a heart block, who successfully underwent renal lithotripsy,
      without cardiac pacemaker, is reported.

PMID- 9253576
TI  - Accidental subdural injection of local anaesthetic: diagnosis by pressure
      measurement and response to aspiration of injectate.
AB  - A healthy 22-year-old man received an initial injection of 12 mL of
      lignocaine/bupivacaine solutions (2 mL test, then 10 mL) into an epidural
      catheter. This produced a satisfactory regional blockade that seemed to be
      epidural but, when a supplementary 6 mL injection was given 1 h later, the
      patient developed impaired motor function as far as the upper cranial nerves,
      with loss of pinprick sensation to the shoulder. The emergence of fluid dribbling
      freely from the catheter prompted measurement of the pressure, which was 36 mmHg.
      The fluid was proved not to be cerebrospinal fluid (CSF) by the absence of
      glucose (on dextrostix), by the appearance of turbidity with added thiopentone,
      and later by microscopy. Slow aspiration of 7 mL of the presumed injectate
      reduced the pressure in the catheter to 8 mmHg, which promptly reversed the
      additional excessive blockade, allowing surgery to proceed uneventfully. The
      retrieval of injectate argues strongly that the catheter tip had found its way
      subdurally, and the promptness of the reversal with aspiration argues for a
      mechanical rather than a pharmacological cause for the extensive neurological
      dysfunction after the second injection. Pressure measurement and aspiration may
      be helpful in other similar cases.

PMID- 9253575
TI  - Living related small bowel transplantation: anaesthesia and peri-operative care.
AB  - The peri-operative management of the only surviving case, to date, of living
      related small bowel transplantation is described. The anaesthetic technique was
      chosen to optimize hepato-splanchnic blood flow. Peri-operative splanchnic blood
      flow was measured and alterations in flow with changes in inotropic agents and
      volume loading monitored. There appears to be a role for the use of dopexamine
      and aggressive volume loading.

PMID- 9253578
TI  - Chondronecrosis of the cricoid cartilage after intubation. Two case reports.
AB  - Chondronecrosis of the cricoid cartilage is a rare complication of intubation.
      The records of two children were reviewed. An 8-month-old girl with
      myelomonocytic leukaemia developed chondronecrosis 10 days after a 2-day period
      of ventilation. A 4-year-old girl comatose after poisoning by the histamine
      antagonist, alimemazine, developed chondronecrosis after a 2-day period of
      intubation. The complication was suspected when extubation led to dyspnoea owing
      to laryngeal stridor and was confirmed by direct laryngoscopy. We review the
      development of the condition, the causative factors, treatment and prevention.

PMID- 9253579
TI  - A complication of percutaneous tracheostomy whilst using the Combitube for airway
      control.
AB  - We report the occurrence of oesophageal perforation and dilatation during
      percutaneous tracheostomy. The Combitube was used for airway maintenance during
      this procedure. This case highlights the limitations of the Combitube when used
      in this situation.

PMID- 9253580
TI  - Physostigmine: going ... going ... gone? Two cases of central anticholinergic
      syndrome following anaesthesia and its treatment with physostigmine.
AB  - Two patients presented with very different signs of central anticholinergic
      syndrome following general anaesthesia for which they had received premedication
      with hyoscine. Both responded dramatically to 1 mg of intravenous (i.v.)
      physostigmine, which produced a rapid return to a normal level of consciousness.
      The aetiology of central anticholinergic syndrome is multi-factorial, but the
      diagnosis should be considered in all patients who demonstrate abnormal post
      anaesthetic awakening. It is recommended that 1 mg of intravenous physostigmine
      is a safe and effective treatment for central anticholinergic syndrome, and that
      a supply of this important drug must be kept readily available in the recovery
      area of the operating theatre department.

PMID- 9253581
TI  - Atypical signs of glycine absorption following transurethral resection of the
      prostate: two case reports.
AB  - Two cases of atypical transurethral resection (TUR) syndrome occurring during the
      post-operative course are reported. Atypical clinical events such as confusion,
      drowsiness and sudden hypotension could not be explained by the amount of glycine
      fluid absorption, because in both cases this was less than 1000 mL. However, high
      serum concentrations of glycine were noted without marked hyponatraemia and with
      normal measured osmolalities. We suggest that the absorption of glycine is
      related to its high lipid solubility rather than to its direct passage through an
      evident prostatic effraction or periprostatic extravasation.

PMID- 9253582
TI  - Anaesthesiology manpower in Europe.

PMID- 9253583
TI  - Very long sleep after one dose of clorazepate.

PMID- 9253584
TI  - Avian gastrulation and neurulation are not impaired by the removal of the
      marginal zone at the unincubated blastoderm stage.
AB  - In the present study, we removed the whole area marginalis, Rauber's sickle and
      the peripheral part of the area centralis from unincubated chicken blastoderms
      (st IV, Vakaet, 1962a). By placing a fragment of a quail Rauber's sickle
      (functioning as early gastrulation organizer: Callebaut and Van Nueten, 1994) at
      different places and oriented in different directions on the remaining central
      part of the area centralis, we observed, after in vitro culture, a normal
      embryonic development. This indicates that the area marginalis itself is not
      indispensable for gastrulation and neurulation. Our study also indicates that
      none of the three elementary tissues (Rauber's sickle, endophyll and upper layer)
      of the avian unincubated blastoderm present an irreversible functional polarity.

PMID- 9253585
TI  - Histochemical study of the epithelia of nasal polyps by biotinylated lectins and
      neoglycoprotein. A comparison with the normal human respiratory epithelium.
AB  - Formalin-fixed, paraffin-embedded sections from human nasal polyps and the normal
      respiratory epithelium were glycohistochemically investigated. Three biotinylated
      lectins were used: peanut (Arachis hypogaea) agglutinin (PNA) which, binds to
      terminal galactose (beta 1-3) N-acetylgalactosamine residues that can be unmasked
      by a neuraminidase digestion; wheat germ (Triticum vulgare) agglutinin (WGA),
      which binds to N-acetylglucosamine and N-acetylneuraminic acids; and gorse seed
      (Ulex europaeus) agglutinin (UEA-1), which binds to L-fucose. In addition, the
      presence of accessible galactose (beta 1-3) N-acetylgalactosamine (T-antigen)
      glycan receptors (endolectins) was also assessed. The avidin-biotin-peroxidase
      complex (ABC) and diaminobenzidine (DAB) were used as chromogen. The ciliated
      cells of the normal respiratory epithelium and those of the pseudostratified
      epithelium of nasal polyps possess similar glycohistochemical characteristics
      suggesting no major alterations on the level of lectin-reactive carbohydrate
      epitopes as indicators of cellular glycosylations. Notably, this parameter can
      respond sensitively to changes in cell differentiation or activation. The basal
      and mucus-secreting cells in the two epithelia display different reactivity
      patterns emphasizing the presence of dissimilar sugar residues. Similarly, the
      dysplasia reflecting squamous epithelium of nasal polyps shows a distinct
      staining behaviour, indicative for disparate glycoconjugate display. Thus,
      quantitative differences in the lectin-selective staining of various cell types
      are detectable. The expression of T-antigen-bearing neoglycoprotein binding is
      weak and similar in both the normal epithelium and the pseudostratified
      epithelium lining nasal polyps. Only the most superficial cells of the squamous
      epithelium disclose a moderate labelling with this probe. These results indicate
      that further studies in this field are warranted, employing neoglycoproteins and
      also endolectins from human tissues to correlate glycobiological properties of
      the epithelium of the conducting airways and its diseased forms with functional
      features.

PMID- 9253586
TI  - The capsular ligaments of the wrist.
AB  - Variable descriptions and nomenclatures of the ligaments of the wrist can be
      found in the literature. To verify the multiple concepts advanced about this
      subject and to provide a basis for a better understanding of the individual
      variations of carpal biomechanics, and of the numerous pathomechanical concepts
      found in the literature, this study attempted to report the gross anatomy of the
      capsular carpal ligaments and their variations. Precise dissection of 66
      anatomical preparations enabled to observe the origin, insertion, and number of
      fascicles of the capsular ligaments of the wrist. The anatomy of the capsular
      ligaments of the wrist displayed, besides relatively constant structures,
      considerable individual variations that concerned particularly the ulnocarpal and
      dorsal ligaments. A classification of the specimens according to variations in
      the important wrist ligaments has been advanced and has to be refined by a more
      extensive analysis. The possible influence of these variable configurations upon
      carpal biomechanics, diagnosis, classification and treatment of carpal
      pathologies seems conceivable but still has to be determined.

PMID- 9253587
TI  - Morphological and morphometric aspects of primate cornea: a comparative study
      with human cornea.
AB  - Morphological and morphometric features of the cornea of 13 species of primates
      have been studied in order to determine possible morphological differences
      between them. The existence of relationships between different morphometric
      corneal variables was also examined to establish which variables best defined and
      characterized the cornea. The present aim is to determine which primate cornea
      resembles that of the human being most with a view to possible future clinical
      and experimental studies. The results obtained revealed that all the cornea under
      study presented similar morphological features. The relationship between total
      corneal thickness and corneal epithelial thickness was determined as well as the
      relationship between epithelial thickness, the number of epithelial layers and
      the number of epithelial cells. However, the morphological pattern of Bowman's
      membrane and corneal endothelium differed in the species studied. Finally, the
      study indicates that the chimpanzee and the gorilla are the species with a
      corneal morphometry which is closest to that of the human cornea.

PMID- 9253588
TI  - Topographical distribution of NADPH-diaphorase-positive neurons in the cat's
      claustrum.
AB  - The NADPH-diaphorase histochemical technique was used to visualize the
      morphological features of the NADPH-diaphorase positive cells and fibres, and
      their distribution in both parts of the cat's claustrum. Taking into account the
      size and form of the perikaryon and the dendritic and axonal characteristics, the
      neurons are grouped in different subclasses: large, medium-sized and small. The
      present data suggest the occurrence of two populations of NADPH-diaphorase
      neurons in the claustrum. One population consisting of large and medium-sized
      positive neurons represents the projection neurons while the other population of
      small positive neurons corresponds to the local circuit neurons.

PMID- 9253589
TI  - On the development of Cetacean extremities: II. Morphogenesis and histogenesis of
      the flippers in the spotted dolphin (Stenella attenuata).
AB  - Externally, the flippers of Cetacea resemble fish fins, but their internal
      structure is entirely mammalian. They show, however, some adaptative deviations
      from the typical pattern of the mammalian extremities, the most striking of which
      is an increased number of phalanges. The aim of this study is to describe the
      course of the development of flippers in the spotted dolphin (Stenella attenuata)
      and compare its features with other similar species from an evolutionary
      perspective. Early stages of flipper development were studied histologically.
      Differentiation of cartilaginous anlagens of the skeleton progresses
      proximodistally, condensation in digital rays being evident sooner than
      chondrogenesis in the carpal region. In one specimen, the temporary presence of
      cartilaginous rudiments of two carpal elements, which are not found in adults,
      was observed. At all examined stages, phalangeal number progressively increases
      up to (radial to ulnar) 3, 7, 7, 5, 3 in the most advanced stage. The reason for
      this condition is the specialised function of these limb-like structures. It is a
      classical example of convergence, in which mammalian extremities change their
      form to emulate the fin function. A similar condition is found in another group
      of originally terrestrial animals secondarily fully adapted to the aquatic mode
      of life-Ichyosauria (Reptilia).

PMID- 9253590
TI  - Ultrastructural observations on the human visceral pleura.
AB  - Visceral pleura with underlying lung parenchyma was obtained following
      thoracotomy carried out in 21 patients of both sexes, aged 27-56 years. The
      samples were taken from unaltered lung regions, and were studied using
      transmission electron microscopy (TEM). The main components of the visceral
      pleural tissue complex, mesothelium, basal lamina (BL), elastic membrane (EM),
      and submesothelial connective tissue layer, are described, with special reference
      to their relations with the corresponding structures of the lung interstitium.
      These elements have significant quantitative regional diversities but can be
      recognized in all investigated cases, and show constant structural uniformity.
      Two basic mesothelial cell types, squamous (flat) and cuboidal (high) are
      discerned, based on the differences in size, shape, cell organelles and membrane
      specialization. The cuboidal mesothelial cells are especially characteristic for
      the visceral pleura. In addition, an intermediate mesothelial cell that
      apparently represents a stage in the development of a squamous to a cubiodal
      mesothelial cell is fairly common. For more rarely, degenerative mesothelial
      cells are found.

PMID- 9253591
TI  - Nutrition education for the public. Discussion papers of the FAO Expert
      Consultation. United Nations.

PMID- 9253592
TI  - Risk management and food safety. Report of a Joint FAO/WHO Consultation, Rome,
      Italy, 27 to 31 January 1997. United Nations.

PMID- 9253593
TI  - Residues of some veterinary drugs in animals and foods. Monographs prepared by
      the Forty-Seventh meeting of the Joint FAO/WHO Expert Committee on Food
      Additives. Rome, 4-13 June 1996.

PMID- 9253594
TI  - QTL mapping to QTL cloning: mice to the rescue.

PMID- 9253595
TI  - The mappers' torch song.

PMID- 9253596
TI  - From bench to bedside... but when?

PMID- 9253597
TI  - A physical map of human chromosome 7: an integrated YAC contig map with average
      STS spacing of 79 kb.
AB  - The construction of highly integrated and annotated physical maps of human
      chromosomes represents a critical goal of the ongoing Human Genome Project. Our
      laboratory has focused on developing a physical map of human chromosome 7, a
      approximately 170-Mb segment of DNA that corresponds to an estimated 5% of the
      human genome. Using a yeast artificial chromosome (YAC)-based sequence-tagged
      site (STS)-content mapping strategy, 2150 chromosome 7-specific STSs have been
      established and mapped to a collection of YACs highly enriched for chromosome 7
      DNA. The STSs correspond to sequences generated from a variety of DNA sources,
      with particular emphasis placed on YAC insert ends, genetic markers, and genes.
      The YACs include a set of relatively nonchimeric clones from a human-hamster
      hybrid cell line as well as clones isolated from total genomic libraries. For map
      integration, we have localized 260 STSs corresponding to Genethon genetic markers
      and 259 STSs corresponding to markers orders by radiation hybrid (RH) mapping on
      our YAC contigs. Analysis of the data with the program SEGMAP results in the
      assembly of 22 contigs that are "anchored" on the Genethon genetic map, the RH
      map, and/or the cytogenetic map. These 22 contigs are ordered relative to one
      another, are (in all but 3 cases) oriented relative to the centromere and
      telomeres, and contain > 98% of the mapped STSs. The largest anchored YAC contig,
      accounting for most of 7p, contains 634 STSs and 1260 YACs. An additional 14
      contigs, accounting for approximately 1.5% of the mapped STSs, are assembled but
      remain unanchored on either the genetic or RH map. Therefore, these 14 "orphan"
      contigs are not ordered relative to other contigs. In our contig maps, adjacent
      STSs are connected by two or more YACs in > 95% of cases. With 2150 mapped STSs,
      our map provides an average STS spacing of approximately 79 kb. The physical map
      we report here exceeds the goal of 100-kb average STS spacing and should provide
      an excellent framework for systematic sequencing of the chromosome.

PMID- 9253598
TI  - Resistance to salmonellosis in the chicken is linked to NRAMP1 and TNC.
AB  - Natural resistance to infection with Salmonella typhimurium in mice is controlled
      by two major loci, Bcg and Lps, located on mouse chromosomes 1 and 4,
      respectively. Both Bcg and Lps exert pleiotropic effects and contribute to
      cytostatic/cytocidal activities of the macrophage. Bcg encodes for a membrane
      phosphoglycoprotein designated Nrampl (natural resistance-associated macrophage
      protein 1), which belongs to an ancient family of membrane proteins, Lps has not
      been cloned yet, but its location on mouse chromosome 4 has been refined for
      positional cloning. As in mice, chicken inbred lines differ in their
      susceptibility to infection with Salmonella typhimurium. We have tested the
      candidacy of the chicken homologs of Nrampl and Tnc (a locus closely linked to
      Lps), in the differential resistance of chicken inbred lines to infection with S.
      typhimurium. We have first analyzed six inbred chicken lines of Salmonella
      resistant or Salmonella-susceptible phenotypes for the presence of nucleotide
      sequence variations within the coding portion of NRAMP1. We have identified 11
      sequence variations within NRAMP1 in the chicken inbred lines tested: 10 of these
      represented either silent mutations or conservative changes. However, one G-->A
      substitution at nucleotide 696 resulted in the nonconservative replacement of
      Arg223 to Gln223 within the predicted TM5-6 region. This allelic variant was
      specific to the susceptible line C and not observed in any of the resistant
      strains. To investigate the effect of NRAMP1 and TNC on resistance to infection
      with S. typhimurium, 425 (W1 x C)F1 x C chicken progeny were examined during a
      period of 15 days postinfection. Together, NRAMP1 and TNC explain 33% of the
      early differential resistance to infection with S. typhimurium of parental lines
      C and W1. Our data established that resistance to infection with S. typhimurium
      in chickens is inherited as a complex trait and that comparative mapping has
      proven to be useful to identify Salmonella-resistance genes in the chicken.

PMID- 9253599
TI  - Identification and chromosomal localization of human genes containing CAG/CTG
      repeats expressed in testis and brain.
AB  - Human genes containing triplet repeats have been demonstrated to be involved in
      several neurodegenerative diseases by expansion of the repeat in succeeding
      generations. To identify novel genes involved in such pathologies, we have
      isolated transcripts containing (CAG/CTG)n repeats using two approaches. First,
      we screened 4 x 10(6) clones representing 10 copies of a human testis cDNA
      library using a (CAG)14 oligonucleotide probe. Among the 910 clones identified,
      the 243 clones with the strongest hybridization signal were sequenced partially
      from 3' or 5' ends. This provided us with 251 partial sequences that grouped into
      clusters corresponding to 39 genes, of which 19 represent unknown species.
      Second, we selected 203 additional ESTs containing (CAG/CTG)n repeats
      representing 121 clusters from the IMAGE consortium infant brain cDNA library.
      From these two series of sequences, we have localized 95 genes on human
      chromosomes using a panel of whole genome radiation hybrid (Genebridge 4). These
      genes are located on all of the chromosomes except for chromosome X, the highest
      density being observed on chromosome 19.

PMID- 9253600
TI  - Characterization of Alu repeats that are associated with trinucleotide and
      tetranucleotide repeat microsatellites.
AB  - The association of subclasses of Alu repetitive elements with various classes of
      trinucleotide and tetranucleotide microsatellites was characterized as a first
      step toward advancing our understanding of the evolution of microsatellite
      repeats. In addition, information regarding the association of specific classes
      of microsatellites with families of Alu elements was used to facilitate the
      development of genetic markers. Sequences containing Alu repeats were eliminated
      because unique primers could not be designed. Various classes of microsatellites
      are associated with different classes of Alu repeats. Very abundant and poly(A)
      rich microsatellite classes (ATA, AATA) are frequently associated with an
      evolutionarily older subclass of Alu repeats, AluSx, whereas most of GATA and CA
      microsatellites are associated with a recent Alu subfamily, AluY. Our
      observations support all three possible mechanisms for the association of Alu
      repeats to microsatellites. Primers designed using a set of sequences from a
      particular microsatellite class showed higher homology with more sequences of
      that class than probes designed for other classes. We developed an efficient
      method of prescreening GGAA and ATA microsatellite clones for Alu repeats with
      probes designed in this study. We also showed that Alu probes labeled in a single
      reaction (multiplex labeling) could be used efficiently for prescreening of GGAA
      clones. Sequencing of these prescreened GGAA microsatellites revealed only 5% Alu
      repeats. Prescreening with primers designed for ATA microsatellite class resulted
      in the reduction of the loss of markers from approximately 50% to 10%. The new
      Alu probes that were designed have also proved to be useful in Alu-Alu
      fingerprinting.

PMID- 9253601
TI  - A transcript map for the 2.8-Mb region containing the multiple endocrine
      neoplasia type 1 locus.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in
      which affected individuals develop multiple parathyroid, enteropancreatic, and
      pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on
      chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb
      interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity
      studies in MEN 1 and sporadic tumors suggest that the MEN1 gene encodes a tumor
      suppressor and have helped to narrow the location of the gene to a 600-kb
      interval between PYGM and D11S449. Focusing on this smaller MEN1 interval, we
      have identified and mapped 12 transcripts to this 600-kb region. A precise
      ordered map of 33 transcripts, including 12 genes known to map to this region,
      was generated for the 2.8-Mb D11S480-D11S913 interval. Fifteen candidate genes
      (of which 10 were examined exhaustively) were evaluated by Southern blot and/or
      dideoxy fingerprinting analysis to identify the gene harboring disease-causing
      mutations.

PMID- 9253602
TI  - An approximately 1.2-Mb bacterial artificial chromosome contig refines the
      genetic and physical maps of the lurcher locus on mouse chromosome 6.
AB  - Lurcher (Lc) is a semidominant mouse mutant that displays a characteristic ataxia
      in the heterozygous state beginning in the third postnatal week. This symptom
      results from a neurodegenerative event in the cerebellum: There is a catastrophic
      loss of Purkinje cells in the heterozygote animal between postnatal days 10 and
      15. In an effort to identify the genetic lesion borne by Lc mice, we initiated a
      cloning project based on the position of the Lc mutation on mouse chromosome 6.
      We have extended our previous analysis of the genomic segment containing the Lc
      locus by isolating a set of stable and manipulable genomic clones called
      bacterial artificial chromosomes (BACs) that cover this region of mouse
      chromosome 6. These clones provided a good substrate for the isolation of markers
      that were used to refine the physical map of the locus. Furthermore, 20 of these
      markers were mapped onto our (B6CBACa-AW-J/A-Lc x CAST/Ei)F1 x B6CBACa-AW-J/A
      backcross, refining the genetic map and identifying two nonrecombinant markers
      (D6Rck354 and D6Rck355). These two markers, in conjunction with the closest
      flanking markers, were used to identify a 110-kb genomic segment that contains
      all four markers and hence contains the Lc locus. This small genomic segment,
      covered by multiple BACs, sets the stage for the final effort of this project-the
      identification of transcripts and of the mutation within the Lc locus.

PMID- 9253604
TI  - Genotator: a workbench for sequence annotation.
AB  - Sequencing centers such as the Human Genome Center at LBNL are producing an ever
      increasing flood of genetic data. Annotation can greatly enhance the biological
      value of these sequences. Useful annotations include possible gene locations,
      homologies to known genes, and gene signal such as promoters and splice sites.
      Genotator is a workbench for automated sequence annotation and annotation
      browsing. The back end runs a series of sequence analysis tools on a DNA
      sequence, handling the various input and output formats required by the tools.
      Genotator currently runs five different gene-finding programs, three homology
      searches, and searches for promoters, splice sites, and ORFs. The results of the
      analyses run by Genotator can be viewed with the interactive graphical browser.
      The browser displays color-coded sequence annotations on a canvas that can be
      scrolled and zoomed, allowing the annotated sequence to be explored at multiple
      levels of detail. The user can view the actual DNA sequence in a separate window;
      when a region is selected in the map display, it is highlighted automatically in
      the sequence display, and vice versa. By displaying the output of all of the
      sequence analyses, Genotator provides an intuitive way to identify the
      significant regions (for example, probable exons) in a sequence. Users can
      interactively add personal annotations to label regions of interest. Additional
      capabilities of Genotator include primer design and pattern searching.

PMID- 9253603
TI  - Detection of RAPD markers correlated with chloroquine resistance in Plasmodium
      falciparum.
AB  - We described the use of the random amplified polymorphic DNA (RAPD) technique on
      Plasmodium falciparum DNA to detect genetic markers for chloroquine-resistant
      strains. Fourteen RAPD primers were tested, three of which generated banding
      patterns correlated with chloroquine resistance. To measure this correlation, the
      RAPD profiles were analyzed using the Nei and Li similarity coefficient.
      Detection of distinctive RAPD bands allowed us to synthesize specific PCR primers
      to be used on whole-blood samples. Two primer sets were synthesized and tested on
      sensitive and resistant strains for their ability to amplify the DNA fragment
      corresponding to the RAPD marker. These results suggest that RAPD and PCR
      techniques can be used as powerful tools for the detection of genetic markers
      associated with drug resistance.

PMID- 9253614
TI  - Cytogenetic analysis of Liza ramada (Pisces, Perciformes) by different staining
      techniques and fluorescent in situ hybridization.
AB  - A cytogenetic investigation was carried out on specimens of Liza ramada, a
      mugilid species common in the Mediterranean sea. The analysis of chromosomes was
      performed through Ag-staining, C-banding, chromomycin A3 and DAPI staining, and
      fluorescent in situ hybridization with ribosomal genes. The results obtained are
      discussed with respect to cytotaxonomic implications and to the features of NORs.

PMID- 9253615
TI  - Genetic differentiation among natural populations of the Nile tilapia Oreochromis
      niloticus (Teleostei, cichlidae).
AB  - We analysed the genetic differentiation among 17 natural populations of the Nile
      tilapia Oreochromis niloticus (Linnaeus, 1758) using allozymes and restriction
      fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA). The populations
      studied, from the River Senegal to Lake Tana and from Lake Manzalla to Lake
      Baringo, represent all subspecies which have been previously described. Sixteen
      variable nuclear loci showed that these populations can be clustered in three
      groups: (1) West African populations (Senegal, Niger, Volta and Chad drainages),
      (2) Ethiopian Rift Valley populations (Lakes Awasa, Ziway, Koka and the Awash
      River) and (3) Nile drainage (Manzalla, Cairo, Lake Edward) and Kenyan Rift
      Valley populations (Lakes Turkana, Baringo and River Suguta). Nine different
      mtDNA haplotypes were found in the RFLP analysis of a 1 kb portion of the D-loop
      region. The network obtained showed that there are three geographically distinct
      groups; all West African populations and O. aureus are clustered, the two
      Ethiopian Rift Valley populations are distinct and between these two groups are
      the Kenyan and Ugandan Rift Valley populations. Nile populations show affinities
      both with West African populations and with specimens from Lakes Tana and
      Turkana. Taxonomic and biogeographical implications of these results are
      discussed.

PMID- 9253618
TI  - Histopathological changes in bone marrow biopsies from patients with chronic
      myeloid leukaemia after treatment with recombinant alpha-interferon.
AB  - AIMS: Recombinant alpha-interferon (r-IFN) is an effective therapy for chronic
      myeloid leukaemia (CML), inducing haematological and major cytogenetic response
      in 70% and 30% of patients, respectively. In this study we have evaluated the
      significance of bone marrow (BM) histology on the subsequent response to r-IFN
      therapy, as well as the morphological changes induced by r-IFN within BM. METHODS
      AND RESULTS: 73 BM biopsies were studied from 21 patients with Ph1-positive CML
      in chronic phase at diagnosis and at different times during r-IFN treatment. At
      diagnosis the probability of achieving a major or complete cytogenetic response
      was significantly higher in patients with a total marrow cellularity lower than
      90% (P = 0.02). During therapy with r-IFN, significant BM changes included
      disappearance of the CML pattern (P = 0.0002), reduction of M:E ratio (P =
      0.0009) and total cellularity (P = 0.0027), and increase in number of terminal
      megakaryocytes (P = 0.0009) and of fatty tissue regeneration (P = 0.037); only
      after long-term therapy (mean 20 months), did reticulin fibrosis increase
      significantly (P = 0.032). CONCLUSIONS: The overall BM morphology in response to
      treatment displayed different pictures, ranging from persistence of CML (25
      biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence
      of diffuse morphological abnormalities was associated with lack of cytogenetic
      responsiveness (P = 0.025).

PMID- 9253619
TI  - Static and dynamic bone changes in hospitalized patients suffering from rickets-
      a histomorphometric study.
AB  - AIMS: The aim of this study was to assess static and dynamic bone changes in
      patients suffering from rickets. METHODS AND RESULTS: Transcortical iliac crest
      biopsies of 15 hospitalized children with rickets were taken after labelling new
      bone formation with two cycles of tetracycline administration 10 days apart.
      Undecalcified sections were prepared, appropriately stained and histomorphometric
      analysis performed. Static and dynamic bone changes were measured including the
      volume of bone and osteoid, trabecular and cortical bone dimensions and
      resorptive and mineralization activities. The results were compared with normal
      values. The nature of the mineralization fronts was noted. Trabecular osteoid
      volumes of all but one patient was above the normal range of 1.9% (+/-0.4%). This
      patient suffered rickets associated with the Kwashiorkor-Marasmus syndrome.
      Tetracycline labelling was found to be more sensitive than subjective evaluation
      of the nature of the mineralization fronts. Despite a balanced hospital diet, a
      bone formation rate of zero was found in three cases, indicating a need for
      vitamin D and mineral supplementation. Seven cases had decreased mineralization
      lag times, indicating response to the balanced diet. CONCLUSIONS: This study
      showed that histometric analysis of labelled bone biopsies is a helpful adjunct
      to the diagnosis but particularly assessment of response to management of
      deficiency states in children.

PMID- 9253620
TI  - Tumoral calcinosis: a clinicopathological study of 111 cases with emphasis on the
      earliest changes.
AB  - AIMS: To study the pathogenesis of tumoral calcinosis (TC), we investigated 111
      cases registered in Zaire over 30 years. METHODS AND RESULTS: The patients were
      108 black Africans and three Caucasians between 3 and 74 years of age (mean,
      37.7; median, 39). The gender was known in 33 males and 46 females; in 79 the
      gender was unknown. All but three were healthy and one had tuberculosis. The
      majority presented with a painless swelling in single or multiple periarticular
      regions. The hip was the most commonly affected (57%). Seven recurrences after
      surgical removal of the mass were reported. On microscopic examination, lesions
      were classified as follows: 24% stage I, 16% stage II and 60% stage III depending
      on the cellular activity at the border of the cysts. In five stage I cases only,
      and in no advanced stage II/III lesions, were exuberant cellular proliferative
      changes seen adjacent to the classical cystic form. These consisted of either ill
      defined reactive-like perivascular solid cell nests admixed with mononuclear and
      iron-loaded macrophages, or well-organized variably sized fibrohistiocytic
      nodules embedded in a dense collagenous stroma. These immature changes indicated
      newly appearing lesions and were assumed to represent the earliest discernible
      stages in the evolution of TC. The unique well-defined fibrohistiocytic nodules
      have not been described previously. CONCLUSIONS: These findings have thus
      described the full spectrum of lesions occurring in TC. We believe that the
      adjacent findings are potentially important either in recognizing early stages of
      the disease or in understanding its pathogenesis.

PMID- 9253621
TI  - Value of thrombomodulin immunostaining in the diagnosis of mesothelioma.
AB  - AIMS: Even with the benefit of immunohistochemistry and electron microscopy, the
      differential diagnosis between epithelial mesothelioma and pulmonary
      adenocarcinoma is often difficult. In most instances, the diagnosis of
      mesothelioma must be reached by the use of immunohistochemical markers that react
      with adenocarcinomas, but not with mesotheliomas. The purpose of this study is to
      determine the value of thrombomodulin (TM) as a positive marker for mesothelioma
      when distinguishing epithelial pleural mesothelioma from pulmonary
      adenocarcinoma. METHODS AND RESULTS: TM was expressed in 28 (80%) of 35
      epithelial pleural mesotheliomas, but only five (10.9%) of 46 pulmonary
      adenocarcinomas had appreciable reactivity for this marker. CONCLUSION: It is
      concluded that TM can be useful in separating pulmonary adenocarcinoma from
      epithelial mesothelioma, but it should be used only in conjunction with other
      immunohistochemical markers that are currently employed in distinguishing between
      these two types of malignancies.

PMID- 9253622
TI  - Immunohistochemical differentiation of metastases of renal carcinomas versus
      other carcinomas with anti-gamma GT monoclonal antibody 138H11.
AB  - AIMS: Adenocarcinomas account for about 60% of metastatic cancers of unknown
      primary (CUP) site. In such a clinical CUP situation, histopathologists are
      challenged to differentiate renal cell carcinomas (RCC) from other
      adenocarcinomas with similar immunophenotypes, especially chemotherapeutically
      treatable mammary and ovarian carcinomas. METHODS AND RESULTS: Recently, we
      produced a monoclonal antibody (mAb), designated 138H11, against human gamma
      glutamyl-transferase (gamma GT), which stained over 98% primary clear cell and
      chromophilic RCC on frozen sections. The 138H11 epitope could not be stained
      using conventional techniques in most paraffin-embedded sections of the same
      origin, due to destruction by formalin fixation below the detection level. Here,
      we demonstrate that mAb 138H11 can specifically stain gamma GT in paraffin
      embedded primary and metastatic RCC after enhancement with an ultrasensitive
      immunohistochemical method. We analysed a selected subgroup of adenocarcinomas
      with immunophenotypes which would not allow a differentiation from RCC in a CUP
      situation. We found a predominantly membranous expression of the 138H11 target
      antigen in 26/51 primary RCC and 15/ 34 metastatic RCC. In contrast, all 43/43
      primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian,
      mammary, bronchial and gastric carcinomas were negative for mAb 138H11.
      CONCLUSIONS: The data suggest that mAb 138H11 is useful for the
      immunohistochemical differentiation of RCC from other metastatic adenocarcinomas
      if the primary site of the tumour is not known.

PMID- 9253623
TI  - Pigmented renal cell carcinoma: accumulation of abnormal lysosomal granules.
AB  - AIMS: Five cases of renal cell carcinoma (RCC) with abnormal pigmentation have
      been examined by histochemical, immunohistochemical and ultrastructural methods.
      METHODS AND RESULTS: Compared with conventional RCCs, there was no difference in
      histological findings of each case, except for the presence of pigmented cells.
      In three cases, tumour cells possessing various sized brown granules with
      neuromelanin-like features were scattered throughout the tumour. The granules
      observed in one of the others were angulated lysosomes and in another tumour
      cells in the pigmented areas possessed the granules closely resembling those of
      granular cell tumour. However, melanosome or neurosecretory granules could not be
      detected in any of the cases examined. In three cases, some of these abnormal
      granules showed a weak acid phosphatase activity. On immunohistochemical
      examination, tumour cells showed a positive immunoreaction for epithelial markers
      and lacked any antigens suggesting neuroectodermal or neuroendocrine
      differentiation. The granules in three cases were faintly positive for lysozyme
      and KP-1. CONCLUSIONS: These findings indicate that abnormal pigmentation of RCCs
      examined in this study is attributed to accumulation of abnormal lysosomal
      granules in the neoplastic cells.

PMID- 9253624
TI  - Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of
      hepatocellular carcinoma, a report of four cases.
AB  - AIMS: Four cases of hepatoid adenocarcinoma, three in the stomach, and one in the
      sigmoid colon, are presented to emphasize venous permeation and mimicry of
      hepatocellular carcinoma by metastatic liver nodules. METHODS AND RESULTS: Tumour
      cells in all cases extensively invaded vems, and intravenous tumour thrombi in
      two cases were grossly observed as anastomosing, worm-like cords up to 10 mm in
      diameter in the lesser omentum and mesentery in continuity with the primary
      mucosal lesions. The cytological features and trabecular architecture of the
      metastatic liver nodules in these subjects mimicked primary hepatocellular
      carcinoma. In a third case the tumour contained grossly visible bile in a
      metastatic lung nodule, but there was no evidence of bile production in the
      primary gastric or metastatic liver lesions. In the fourth case, detailed
      histopathological study revealed a gastric origin of the hepatoid adenocarcinoma,
      rather than primary hepatocellular carcinoma metastatic to the stomach, the
      initial diagnosis. CONCLUSIONS: These cases are reported here to draw attention
      to this rare variant of gastrointestinal adenocarcinoma, its mimicry of
      hepatocellular carcinoma when metastatic to the liver and other sites, and its
      propensity for venous permeation.

PMID- 9253625
TI  - Intra-vascular tumour in pleomorphic adenomas--a report of four cases.
AB  - AIMS: The aim of this study was to report four cases of pleomorphic adenoma which
      were characterized by intra-vascular tumour. METHODS AND RESULTS: The patients
      ranged in age from 13-43 years, one was male while three were female. The tumours
      were situated in the parotid gland, submandibular gland and palate (two cases).
      The intra-vascular tumour consisted of single, clustered and solid cords of cells
      within multiple muscular walled blood vessels and capillaries both in the capsule
      and in the tumour. Immunoperoxidase staining confirmed that the intra-vascular
      cells were phenotypically identical to those of the tumour. The possibility that
      the intra-vascular tumour represents artefactual 'spillage' has been considered,
      however there is some histological evidence suggesting that this phenomenon
      represents true vascular invasion. CONCLUSIONS: The biological significance of
      intra-vascular tumour in pleomorphic adenomas is unknown. Thus far there has been
      no correlation with either recurrence or metastases.

PMID- 9253626
TI  - Reliability of rectal biopsy in distinguishing between chronic inflammatory bowel
      disease and acute self-limiting colitis.
AB  - AIMS: In order to assess the validity of previously proposed criteria for the
      differentiation of chronic inflammatory bowel disease (CIBD) from acute self
      limiting colitis (ASLC) all rectal biopsies were reported by a single
      histopathologist with a long-term gastrointestinal interest over a 4.5-year
      period. METHODS AND RESULTS: The presence or absence of distorted crypt
      architecture, increased lymphocytes and plasma cells, villous mucosal
      architecture, granulomata, basal lymphoid aggregates, basal giant cells and
      Paneth cell metaplasia was noted for each biopsy. The definite presence of any of
      the above features, with the exception of intramucosal granulomata, was regarded
      as indicative of CIBD. Eighteen months later all available case notes were
      examined and the presenting clinical symptoms and working clinical diagnosis
      extracted. The final diagnosis, histopathological diagnosis and the presence or
      absence of any of the above histopathological features were correlated and the
      positive predictive value of each histopathological feature was calculated. A
      correct diagnosis of either CIBD or ASLC was made in 80 of 84 and 29 of 31 cases,
      respectively. CONCLUSIONS: Villous mucosal architecture and Paneth cell
      metaplasia were found to be specific features of CIBD. Distorted crypt
      architecture, basal lymphoid aggregates and plasma cell infiltration of the
      lamina propria were also useful features but strict definition of these features
      is required and discussed. Intramucosal epithelioid granulomas were identified in
      eight cases of CIBD and four cases of ASLC. In association with ruptured crypts
      intramucosal granulomas are not specific features of Crohn's colitis.

PMID- 9253627
TI  - Diagnostic value of inhibin immunoreactivity in ovarian gonadal stromal tumours
      and their histological mimics.
AB  - AIMS: Inhibin is a heterodimeric protein hormone which appears to be a sensitive
      serological and immunohistochemical marker of ovarian granulosa cell tumours. The
      purposes of this study were to examine inhibin immunoreactivity in a wide range
      of gonadal stromal neoplasms and to assess its value in the differential
      diagnosis of problematic ovarian tumours. METHODS AND RESULTS: Inhibin
      immunostaining was identified in eight cases of stromal hyperthecosis, 24 adult
      type granulosa cell tumours, two juvenile granulosa cell tumours, nine Sertoli
      cell or Sertoli-Leydig cell tumours, one gynandroblastoma, three gonadoblastomas,
      two cases of sex cord tumour with annular tubules, two steroid cell tumours and
      two sclerosing stromal tumours. Inhibin was also present in 4/6 fibrothecomas and
      2/3 unclassified gonadal stromal tumours. There was no staining of neoplastic
      cells in any of the problematic ovarian tumours, in many of which a diagnosis of
      gonadal stromal tumour had been initially considered. However, inhibin was
      detected in reactive stromal cells in many cases. CONCLUSIONS: Inhibin is a
      sensitive immunohistochemical marker of a wide range of gonadal stromal tumours
      and is of value in the differential diagnosis of ovarian neoplasia.

PMID- 9253629
TI  - Human immunodeficiency virus type 1 in an unusual cystic lymphoepithelial lesion
      of the lung.
AB  - AIMS: We present the clinical and histopathological findings of an unusual
      pulmonary cystic lymphoepithelial lesion in an HIV sero-positive patient. METHODS
      AND RESULTS: The 32-year-old female patient developed two nodules in the vicinity
      of the right and left hila. Left upper lobectomy showed a 40-mm wide cystic
      lesion. The cyst wall was lined by a squamous epithelium and lymphoid tissue with
      a marked follicular hyperplasia and a prominent follicular cell dendritic network
      expressing HIV major core protein p24. CONCLUSIONS: The absence of an Epstein
      Barr virus infected lymphoid population and monoclonal immunoglobulin gene
      rearrangement supported the benign nature of the lesion.

PMID- 9253628
TI  - Lymphoepithelioma-like salivary gland carcinoma in Taiwan: a clinicopathological
      study of nine cases demonstrating a strong association with Epstein-Barr virus.
AB  - AIMS: Lymphoepithelioma-like carcinoma (LELC) of the salivary glands is a rather
      rare tumour. Previous studies have shown its strong association with Epstein-Barr
      virus (EBV) among Chinese and Eskimos. We tested this observation with nine
      Chinese patients with salivary gland LELC in Taiwan including one with coexisting
      nasopharyngeal carcinoma (NPC) and studied the prognostic significance of their
      histopathological features. METHODS AND RESULTS: This series showed a
      predilection for female patients and parotid glands with a median age of 50
      years. Three patients died 18.5-26 months after the diagnosis including the case
      with NPC. Six patients were alive without recurrence for 14-45 months with a
      median follow-up of 34.5 months. Histopathologically, the tumours showed either
      lobular or diffuse growth pattern. Granulomas and/or germinal centres were
      observed in most cases and both B- and T-cells were found in the lymphoid
      infiltrates, indicating that the salivary gland LELC was capable of inducing a
      strong host immune reaction. Microscopic growth pattern, lymph node metastasis,
      and presence or absence of granulomas and/or germinal centres seemed to be
      important prognostic factors. Both salivary gland LELC and NPC shared similar
      histopathological appearance and positive immunostaining for epithelial membrane
      antigen and cytokeratin AE1 but not AE3. Granulomas and amyloid might occur in
      both tumours. A nasopharyngeal examination is indicated in patients with salivary
      gland LELC to exclude the possibility of coexisting or metastatic NPC. All nine
      cases showed positive nuclear signals for EBV-encoded RNA by in situ
      hybridization including the case with NPC. CONCLUSIONS: Our study and the
      previously published studies show that the association of salivary gland LELC and
      EBV is strongly related to racial and geographical factors.

PMID- 9253630
TI  - Early adenocarcinoma of the oesophagus and oesophageal cyst.
AB  - AIMS: An increased risk of adenocarcinoma of the oesophagus has been demonstrated
      in patients with long segments of Barrett's mucosa. The risk of cancer associated
      with short segments of metaplasia of the oesophagogastric junction is not known.
      METHODS AND RESULTS: We report a case of early adenocarcinoma of the oesophagus
      arising on short tongues of Barrett's mucosa associated with an oesophageal cyst.
      The patient was a 68-year-old man with no previous clinical history of gastro
      oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead
      to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia.
      On pathological examination of the resected specimen, an early adenocarcinoma had
      developed in Barrett's mucosa, localized just above the oesophageal cyst.
      CONCLUSIONS: As oesophageal cysts can cause symptoms suggestive of reflux, we
      hypothesize that this association may not be fortuitous.

PMID- 9253631
TI  - Nodular erythema elevatum diutinum mimicking cutaneous neoplasms.
AB  - AIMS: We describe the cutaneous pseudoneoplastic lesions in two patients with
      nodular erythema elevatum diutinum, a rare chronic disorder in which polymorph
      nuclear fragmentation (leukocytoclasis) is present within dermal nodules showing
      spindle cells and fibrosis. In both cases diagnostic difficulty was encountered
      clinically and pathologically and various benign and malignant neoplasms were
      considered in the differential diagnosis. METHODS AND RESULTS:
      Immunohistochemically the spindle cells were negative for CAM5.2, AE1/3, S100
      protein and desmin (D33). They were positive for vimentin and focally positive
      for CD34 and alpha-smooth muscle actin. Some of the spindle cells were positive
      for Mac 387 and KP1(CD68). By electron microscopy, the lesions were shown to
      consist of fibroblasts/myofibroblasts and fusiform macrophages. CONCLUSIONS:
      Increased awareness of the features described will help to avoid misdiagnosis as
      a neoplastic process.

PMID- 9253632
TI  - Atypical dermal nodules in benign melanocytic naevi.
AB  - AIMS: The prognosis of deeply invasive melanoma can be poor and to a large extent
      it is unresponsive to treatment once metastases have occurred. It is therefore
      important that any dermal melanocytic lesions that have some features suggestive
      of melanoma but are nevertheless benign, should be identified. METHODS AND
      RESULTS: A series of 40 benign melanocytic naevi is described in which the
      clinical presenting feature was a central focus of increased pigmentation. This
      was found histologically to correspond to dermal nodules of large melanocytes
      showing some, usually mild, nuclear atypia but low indices of cellular
      proliferation. The nodules are found within otherwise typical melanocytic naevi.
      The clinical and histological differential diagnosis included invasive melanoma
      but in follow-up, which is admittedly short (mean 24 months), none have recurred
      or metastasized. CONCLUSIONS: It is suggested that the nodules represent terminal
      differentiation of melanocytes rather than proliferative changes. They should be
      distinguished from melanoma and regarded as a variant of benign melanocytic
      naevi.

PMID- 9253633
TI  - Epithelioid sarcoma masquerading as perforating granuloma annulare.

PMID- 9253634
TI  - Occupational health in Israel.

PMID- 9253635
TI  - Pulmonary metal distribution in urban dwellers.
AB  - To clarify the factors influencing the concentrations and distribution of metal
      elements in the lung, we analyzed the following 8 metals in the 5 lung lobes of
      17 autopsied urban dwellers by flame or flameless atomic absorption spectrometry:
      aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), manganese
      (Mn), copper (Cu), and Zinc (Zn). The arithmetic mean value (in micrograms of
      metal per gram of dry weight) calculated for five lobar metal concentrations in
      each subject ranged from 80 to 681 for Al, from 0.34 to 3.41 for Cd, from 0.41 to
      12.7 for Cr, from 0.22 to 1.93 for Ni, from 0.15 to 1.47 for Pb, from 0.64 to
      2.36 for Mn, from 2.84 to 7.24 for Cu, and from 40.7 to 77.6 for Zn. The eight
      metals were classifiable into two groups on the basis of the interindividual and
      interlobar concentration variations. The first group, consisting of Cu and Zn,
      was characterized by smaller interindividual variations (co-efficient of
      variation, CV < 30%) and smaller inter lobar variations (mean CV < 15%). Their
      levels were not affected significantly by sex, smoking habits, or possible
      occupational exposure to metal-containing dust. In contrast, the second group,
      consisting of Al, Cd, Cr, Ni, Pb, and Mn, exhibited larger interindividual
      variations (CV > 45%) and larger interlobar variations (mean CV > 25%).
      Concentrations of these metals, except for Cd, tended to be higher in the upper
      lobes than in the lower lobes. The concentrations of Al and Cr were significantly
      higher in men than in women. Smoking significantly elevated the levels of Cr, Cd,
      Ni, and Pb, and the concentrations of Al, Cr, Ni, and Mn were higher in subjects
      with possible occupational exposure to metal-containing dust than in those
      without such exposure. However, the interlobar distribution patterns of the
      metals did not seem to be influenced by sex, smoking habits, or occupational
      exposure to metal-containing dust.

PMID- 9253636
TI  - Effect of 3 hours of passive smoke exposure in the evening on inflammatory
      markers in bronchoalveolar and nasal lavage fluid in subjects with mild asthma.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of environmental
      tobacco smoke (ETS) exposure in the evening on inflammatory changes in
      bronchoalveolar (BAL) and nasal lavage (NAL) fluid. METHODS: Ten subjects with
      mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1
      0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or
      ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the
      following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL
      fluids were analyzed for cellular composition and concentrations of histamine,
      albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid,
      tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior
      to and 30 min after exposures, and NAL fluids were analyzed for histamine,
      albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and
      tryptase. RESULTS: There was a significant rise in symptoms after ETS exposure
      compared with sham (P < 0.05). Spirometric lung function did not change during or
      after exposure compared with pre-session values. Visual bronchoscopic scoring
      revealed no significant effect of ETS exposure, nor did BAL cells and mediators
      or NAL mediators as compared with pre-challenge or post-sham values. CONCLUSION:
      In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an
      inflammatory effect detectable in BAL or NAL fluid.

PMID- 9253637
TI  - Effects of occupational use of vibrating tools in the autonomic, central and
      peripheral nervous system.
AB  - OBJECTIVES: The objective of this study was to clarify the autonomic, central and
      peripheral nervous effects of vibrating-tool operation. METHODS: The ECG R-R
      interval variability (CVRR), including the C-CVHF, C-CVLF (two component CVs of
      the CVRR reflecting parasympathetic and sympathetic activities, respectively) and
      the power spectral densities (PSDHF and PSDLF) after autoregressive analysis,
      short-latency somatosensory evoked potentials (SSEP), distribution of nerve
      conduction velocities (DCV), and median and radial nerve conduction velocities
      (NCVs) were measured in 17 vibrating-tool operators and the same number of age
      matched control subjects. Some of the operators complained of white finger even
      in summer as soon as they arrived at the cold workplace. DESIGN: The significance
      of the differences in neurophysiological data between the exposed and unexposed
      groups and the associations between these data in the former were investigated.
      RESULTS: The CVRR, C-CVHF and PSDHF were significantly lower in the vibrating
      tool operators than in the matched controls. The N9-N13 interpeak latency of the
      SSEP, i.e., conduction time of the cervico-spinobulbar pathway, in the operators
      was significantly prolonged as compared with the controls; the faster velocities
      of the DCV and the NCVs were significantly slowed in the operators. The N9-N13
      interpeak latency in the operators was significantly correlated with the C-CVHF.
      CONCLUSION: Complex stressors of local vibration, cold, noise and heavy work,
      seem to affect the cervico-spinobulbar, parasympathetic and peripheral nerve
      functions. Also, parasympathetic hypofunction may imply a consequence in
      brainstem pathology induced by cold exposure in addition to vibration.

PMID- 9253638
TI  - A study of autoantibodies and circulating immune complexes in mercury-exposed
      chloralkali workers.
AB  - Inorganic mercury may cause immunologically mediated disease: e.g.,
      glomerulonephritis, acrodynia, and contact allergy. Animal models have
      demonstrated the importance of genetic factors in determining susceptibility and
      resistance to autoimmunity, as well as the specific manifestation of the
      autoimmune response. Findings in groups of workers with occupational exposure to
      inorganic mercury have been inconsistent. OBJECTIVE: To investigate whether an
      immune response, caused by exposure to inorganic mercury (Hg), could be shown in
      occupationally exposed workers. METHODS: Immunoglobulin G (IgG), antinuclear
      autoantibodies, antibodies against thyroid, stomach or kidney antigens using
      indirect immunofluorescence, antibodies against glomerular basement membrane
      using ELISA, and circulating immune complexes in serum, and albumin in urine,
      were examined in Hg-exposed workers and controls. The two groups, 41 male
      chloralkali workers exposed to Hg vapour (mean exposure time 9 years) and 41
      unexposed controls were age-matched and recruited from the same company. Hg
      concentrations in whole blood (B-Hg), plasma (P-Hg), and urine (U-Hg) were
      determined using cold vapor atomic spectrometry. DESIGN: Cross-sectional study.
      RESULTS: The mean B-Hg, P-Hg and U-Hg levels were 46 nmol/l, 37 nmol/l, and 27
      micrograms/g creatinine in the exposed group, and 17 nmol/l, 6.9 nmol/l, and 3.4
      micrograms/g creatinine in the referents. No statistically significant
      differences were found regarding IgG levels, urinary albumin excretion,
      prevalence of abnormal titers of autoantibodies or circulating immune complexes.
      There were no statistically significant associations between autoantibodies or
      immune complexes on the one hand and mercury exposure indices on the other.
      CONCLUSION: The results indicate that, if and when lasting autoimmune response
      occurs at the mercury exposure levels of the present study, it is uncommon. A
      small fraction of humans may, however, be susceptible to the development of
      autoimmunity, and there is also a possible "healthy worker" selection. Thus cross
      sectional studies of moderate numbers of active workers will have low power to
      demonstrate autoimmune effects.

PMID- 9253639
TI  - Reproducibility of a questionnaire for assessment of present and past physical
      activities.
AB  - OBJECTIVE: The aim of this study was to evaluate the reproducibility of a self
      administered questionnaire about present and past physical activities at work and
      during leisure time. METHODS AND DESIGN: The questionnaire, covering the period
      1970-1993, comprised 12 questions on physical activities at work, and 12, with
      similar wording, for such activities in leisure time. There were also four
      questions on physical training. Two-week reproducibility (test-retest
      reliability) concerning the period 1970-1993 was analysed in a group of 44
      subjects, and 1-year reproducibility, concerning current activities in 1993, was
      analysed in a second group of 123 subjects in relation to gender, age and low
      back health. RESULTS: Test-retest reliability calculated as intraclass
      correlation coefficients (ri) for physical activities at work (ri 0.41-0.98)
      exceeded that for leisure time and physical training activities (ri 0.33-0.68).
      Calculated correlations did not differ markedly between past and present
      activities. No distinct influence of gender or low back health on 1-year
      reproducibility was found, in contrast to a slight tendency towards higher
      reproducibility among subjects of 50 years and older compared with younger
      subjects. CONCLUSIONS: Reproducibility of this questionnaire about physical
      activities at work showed no clear tendency to deteriorate regarding activities
      during the immediately preceding two decades. The questions about physical
      activities during leisure time have to be revised. Reliable retrospective
      information about physical activities in leisure time could perhaps not be
      collected by self-administered questionnaires and other methods, e.g. interview
      based questionnaires, may be more suitable.

PMID- 9253640
TI  - International data base of exposure measurements in the pulp, paper and paper
      product industries.
AB  - An international data base of exposure measurements in the pulp, paper and paper
      product industries was constructed to be used in exposure assessment for
      epidemiology studies and hazard control. Industrial hygiene and biological
      monitoring data were collected from countries participating in the multicentric
      study of the International Agency for Research on Cancer. Each measurement was
      characterized by country, mill type and number, department, job, agent measured,
      sampling method, measurement result in the standard unit, duration and date of
      sampling, assessment of representativeness, measurer, purpose of measurements,
      and remarks (e.g. on measurement sites and biases). Over 31,000 measurement
      results on 246 different chemical agents from 13 countries were available from
      pulp (45% of measurements), paper/paperboard/recycling (12%) and paper product
      (11%) mills or from their non-production departments (23%). Most measurements
      (82%) were carried out after 1980. The most frequently measured group of agents
      was inorganic gases (35%), followed by organic compounds (25%), solvents (18%),
      mineral dusts (12%), metals (6%) and bioaerosols (3%). Over 90% of the
      measurements were without an obvious bias, but their true representativeness is
      difficult to assess. Concentrations of various agents, including sulfur dioxide,
      chlorine dioxide, carbon monoxide, nitrogen dioxide, ozone, ammonia, formaldehyde
      and some solvents, often exceeded current occupational exposure limits. This data
      base summarizes a great deal of previously unpublished exposure data, provides a
      unique opportunity to study exposure patterns at the international level and
      identifies exposure situations that require further attention and investigation.

PMID- 9253641
TI  - Biological monitoring of methylhexahydrophthalic anhydride by determination of
      methylhexahydrophthalic acid in urine and plasma from exposed workers.
AB  - OBJECTIVE: To investigate whether methylhexahydrophthalic acid (MHHP acid) in
      urine and plasma can be used as a biomarker for exposure to
      methylhexahydrophthalic anhydride (MHHPA). METHODS: MHHPA in air was sampled by
      Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation
      detection. MHHP acid in urine and plasma was analysed by GC with mass
      spectrometric detection. Workers occupationally exposed to MHHPA were studied.
      Air levels of MHHPA were determined by personal sampling in the breathing zone.
      Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27
      workers. In eight workers all urine was collected at intervals during 24 h.
      Plasma levels of MHHP acid were determined in 20 workers. RESULTS: The time
      weighted average (TWA) air levels ranged from 5 to 60 micrograms MHHPA/m3 during
      8-h workshifts. The urinary levels of MHHP acid increased during exposure and
      decayed after the end of exposure with an estimated half-life of about 6 h. A
      correlation was found between the TWA air levels of MHHPA and creatinine-adjusted
      MHHP acid levels in urine collected during the last 4 h of exposure. A
      correlation was also seen between the TWA air levels of MHHPA and the plasma
      concentrations of MHHP acid. An exposure to 20 micrograms MHHPA/m3 corresponded
      to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma.
      CONCLUSION: The results indicate that MHHP acid in urine or plasma may be used
      for biological monitoring of the exposure to MHHPA.

PMID- 9253642
TI  - Mortality in a group of tar distillery workers and roofers.
AB  - OBJECTIVE: A retrospective cohort mortality study was conducted to assess long
      term health risk in a group of tar distillery workers and roofers in order to
      investigate the existence of carcinogenic effects related to the occupational
      exposures. METHODS: The study population consisted of 907 tar distillery workers
      and 866 roofers, employed at least one half-year between January 1947 and January
      1980. This group was followed for mortality until January 1988. For the deceased
      workers the cause of death was provided by the Central Bureau of Statistics. The
      observed cause-specific mortality was compared with the expected cause-specific
      mortality calculated by means of the national mortality rates of The Netherlands.
      RESULTS: Mortality from cancer of the lungs and trachea was higher than expected
      in both groups, but not statistically significant. In addition the roofers had
      experienced an excess mortality rate from external causes. CONCLUSIONS: The study
      provides some additional support for the carcinogenicity of coal tar exposures,
      but the findings were not statistically significant.

PMID- 9253643
TI  - The present state of occupational health in Japan.

PMID- 9253644
TI  - Hydrogels of N-acylchitosans and their cellulose composites generated from the
      aqueous alkaline solutions.
AB  - Hydrogels of N-acetyl and N-propionylchitosans were prepared form aqueous
      solutions of sodium N-acylchitosan salts (alkaline N-acylchitosans) and sodium N
      acylchitosan xanthate [O-(sodiumthio)thiocarbonyl N-acylchitosan], respectively,
      by standing at room temperature and on heating. Novel hydrogels of N
      acetylchitosan-cellulose and N-propionylchitosan-cellulose composites were also
      prepared from sodium cellulose xanthate [O-(sodiumthio)thiocarbonyl cellulose]
      solutions mixed with sodium N-acylchitosan salts and with sodium N-acylchitosan
      xanthates, respectively.

PMID- 9253645
TI  - The solution molecular weight and shape of the bacterial exopolysaccharides
      amylovoran and stewartan.
AB  - Amylovoran, the acidic exopolysaccharide (EPS) of Erwinia amylovora, and
      stewartan, the capsular EPS of E. stewartii, were characterized by analytical
      ultracentrifugation and by size exclusion chromatography connected to dual
      detection of light scattering and mass. The average molecular weights of
      amylovoran and stewartan were determined as 1.0 x 10(6) and 1.7 x 10(6) Da, with
      polydispersity values (Mw/M(n)) of 1.5 and 1.4, respectively. Based on the sugar
      composition and their molecular weight, both exopolysaccharides consist of
      approximately 1000 repeating units per molecule, this suggests a similar
      mechanism for chain length determination during biosynthesis of EPS in both
      organisms.

PMID- 9253646
TI  - Influence of thermal history on the stability of gelatin gels.
AB  - Gelatin gel properties have been studied using three techniques. Optical rotation
      measurements have shown that the lower the ageing temperature, the faster the
      helix content increases but the lower the helix stability. Rheological
      measurements show that a small increase in temperature leads to a melting of some
      junction zones followed by a build up of new ones. By ageing the gel at two
      successive temperatures one can show the existence of two populations of junction
      zones with different thermal stabilities. The same result is shown on melting
      thermograms obtained by differential scanning calorimetry. All these results are
      consistent with the hypothesis of the presence of junction zones of various
      lengths, the thermostability of which being proportional to their lengths.

PMID- 9253647
TI  - Qualitative modeling of normal blood coagulation and its pathological states
      using stochastic activity networks.
AB  - We have developed a method for representing biological pathways and simulating
      their behavior based on the use of stochastic activity networks (SANs). SANs, an
      extension of the original Petri net, have been used traditionally to model flow
      systems including data-communications networks and manufacturing processes. We
      apply the methodology to the blood coagulation cascade, a biological flow system,
      and present the representation method as well as results of simulation studies
      based on published experimental data. In addition to describing the dynamic
      model, we also present the results of its utilization to perform simulations of
      clinical states including hemophilia's A and B as well as sensitivity analysis of
      individual factors and their impact on thrombin production.

PMID- 9253648
TI  - Effects of temperature and concentration on bovine lens alpha-crystallin
      secondary structure: a circular dichroism spectroscopic study.
AB  - Elucidation of the structure of alpha-crystallin, the major protein in all
      vertebrate lenses, is important for understanding its role in maintaining
      transparency and its function in other tissues under both normal and pathological
      conditions. Progress toward a unified consensus concerning the tertiary and
      quaternary structures of alpha-crystallin depends, in part, on an accurate
      estimation of its secondary structure. For the first time, three algorithms,
      SELCON, K2D and CONTIN were used to analyze far ultra-violet circular dichroism
      (UV-CD) spectra of bovine lens alpha-crystallin to estimate the secondary
      structure and to determine the effects of temperature and concentration. Under
      all experimental conditions tested, the analyses show that alpha-crystallin
      contains 14% alpha-helix, 35% beta-sheet and the remainder, random coil and
      turns. The results suggest that alpha-crystallin is best classified as a mixed
      protein. In addition, increased temperature and concentration of alpha-crystallin
      result in increased alpha-helices with a compensatory decrease in beta-sheets.
      Such structural alterations in alpha-crystallin may be functionally important
      during terminal differentiation of the lens fiber cells that is accompanied by
      increased protein concentrations and its role as a chaperone-like protein.

PMID- 9253649
TI  - A 13C solid state nuclear magnetic resonance spectroscopic study of cork cell
      wall structure: the effect of suberin removal.
AB  - Solid state 13C NMR measurements of cork, before and after suberin removal,
      showed that aliphatic suberin is spatially separated from carbohydrate and lignin
      and experiences higher motional freedom. Two types of chain methylenes, differing
      in chemical shift and in dynamic properties, were identified in aliphatic
      suberin. Experimental evidence indicated that the more motionally hindered
      methylenes are those situated nearer the linkages of aliphatic suberin to the
      cell wall. These linkages were shown to involve -CH2O- groups, probably engaged
      in ester linkages to phenylpropane units and carbohydrate C6 carbons. Spectral
      intensity changes indicated that, during the first steps of alkaline
      desuberization, these linkages are broken and the shorter aliphatic suberin
      chains removed. Longer chains require hydrolysis of the ester linkages within the
      chains and are removed upon stronger alkaline treatment. T1(C), T1 rho (H) and T1
      rho (C) relaxation times have shown that the removal of suberin from cork leads
      to a motionally restricted and more compact environment, on the megahertz and mid
      kilohertz timescales. The properties of cork suberin showed that suberin
      organization in cork is distinct from that in potato tissue.

PMID- 9253650
TI  - Kinetics of irreversible inhibition of yeast alcohol dehydrogenase during
      modification by 4,4'-dithiodipyridine.
AB  - The course of inactivation of yeast alcohol dehydrogenase (YADH) using 4,4'
      dithiodipyridine (DSDP) has been studied in this paper. The results show that the
      reaction mechanism between DSDP and YADH is a competitive, complexing inhibition.
      The microscopic constants for the inactivation of the free enzyme and the enzyme
      substrate complex were determined. The presence of the substrate NAD+ offers
      strong protection for this enzyme against inactivation by DSDP. The above results
      suggest that two Cys residues are essential for activity and are situated at the
      active site. These essential Cys residues should be Cys-46 and Cys-174 which are
      ligands to the catalytic zinc ion. Another Cys residue, which can be modified by
      DSDP, is non-essential for activity of the enzyme.

PMID- 9253651
TI  - Identifying the G protein, Gz alpha, and its associated proteins in nervous
      tissue using mass spectrometry and microsequencing techniques.
AB  - The signaling pathway associated with pertussis and cholera toxin sensitive G
      proteins have been extensively investigated. In contrast, the function and
      associated signal transduction cascade for the pertussis toxin insensitive G
      protein, Gz alpha have remained elusive. Therefore, the aim of this study was to
      identify the signal transduction pathway associated with Gz alpha by using the
      protein identification techniques of matrix assisted laser desorption ionization
      time of flight mass spectroscopy and N-terminal Edman sequencing. We have chosen
      this technique to identify proteins that Gz alpha associates with and to gain
      insights into the potential role this G protein plays in cells. As Gz alpha is
      predominantly localized in neuronal tissues, homogenates of whole brain tissue
      were used. Gz alpha and its associated proteins were immunoprecipitated from
      brain tissue and identified. The immunoprecipitation of four proteins (140, 46,
      41 and 36 kDa) was shown to be inhibited in the presence of the Gz alpha peptide.
      These proteins were subsequently identified as phospholipase C (PLC)-gamma, beta
      or gamma-actin, Gz alpha and G beta, the beta subunit of heterotrimeric G
      proteins, respectively. These results suggest that Gz alpha exists in a protein
      complex with the actin cytoskeleton and an important intracellular signalling
      enzyme, PLC-gamma. These methods are powerful techniques for determining protein
      protein interactions, and provide the first step to the identification of
      signalling proteins that Gz alpha associates with. However further
      experimentation will be required to determine the biological relevance of these
      protein interactions.

PMID- 9253652
TI  - Cloning of a new chicken trkC extracellular isoform and its mRNA expression in E9
      sensory and autonomic ganglia.
AB  - Neuronal development and maintenance are regulated by trophic interactions with
      the target tissues and the innervating nerve. The neurotrophin family of
      polypeptide growth factors, consisting of nerve growth factor (NGF), brain
      derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5
      (NT-4/5), are produced in limited amounts in target areas. They bind to tyrosine
      receptor kinases of the trk family, including trkA, trkB and trkC, which mediate
      intracellular signalling in the responding neurons. There are reports of
      different isoforms of trkA, trkB and trkC having different signalling capacities.
      This study reports a novel deletion of the first cysteine-rich domain in the
      extracellular part of chicken trkC. We describe the mRNA expression of this
      isoform compared to non-deleted forms in E9 peripheral ganglia studied by
      reversetranscriptase-polymerase chain reaction (RT-PCR) and in situ
      hybridization. We also compare the mRNA expression pattern of two existing signal
      peptide sequences and the distribution of trkC mRNA detected by the use of a
      kinase specific probe. The results show that the novel isoform is expressed in
      peripheral sensory and autonomic ganglia. Moreover both signal peptide forms are
      detected in these ganglia by RT-PCR. In addition, in situ hybridization results
      showed a weak mRNA expression of the novel isoform in the E9 dorsal root ganglion
      (DRG) but not in Remak's ganglion. The two existing signal peptides are equally
      expressed in the DRG and Remak's ganglion, at labelling densities comparable to
      those for the full-length catalytic form of trkC.

PMID- 9253653
TI  - Myelin proteolipid DM20: evidence for function independent of myelination.
AB  - DM20 is a proteolipid protein that has been extensively studied for its role in
      central nervous system myelination. We demonstrate that DM20 expression is
      widespread and independent of myelination. In the Schwann cells and neurons of
      the peripheral nervous system, DM20 is not incorporated into the membrane as it
      is in the central nervous system (CNS), but remains cytoplasmic. Mutations that
      severely reduce the amount of DM20 mRNA in CNS myelinating cells have little
      effect on DM20 expression in nonmyelinating cells of the peripheral nervous
      system and embryonic CNS. Most importantly, the combination of wild-type DM20
      from the endogenous X-linked gene and mutant DM20 expressed from an autosomal
      transgene results in embryonic lethality. We propose a function for DM20 to
      explain these diverse findings based on the ability of DM20 to form multimeric
      complexes, and hypothesize that the DM20 complex participates in intracellular
      molecular transport.

PMID- 9253654
TI  - Phosphorylation events mediated by protein kinase C alpha and epsilon participate
      in regulation of tau steady-state levels and generation of certain "Alzheimer
      like" phospho-epitopes.
AB  - Hyperactivation of protein kinase C (PKC) in intact neuroblastoma cells by
      several methods increases site-specific tau phosphorylation as shown by increases
      in paired helical filament-I (PHF-I) and ALZ-50 but not AT-8 immunoreactivity. In
      the present study, the influence of PKC on tau metabolism was further examined by
      isoform-specific antisense oligonucleotide-mediated PKC downregulation in human
      SH-SY-5Y neuroblastoma cells and by generation of stably-transfected subclones
      expressing isoform-specific anti-PKC mRNA sequences. Downregulation of PKC
      epsilon by both of these methods reduced PHF-I and ALZ-50 immunoreactivity,
      suggesting that this PKC isoform, perhaps via downstream kinase cascades,
      regulated tau phosphorylation events that normally generate these epitopes. By
      contrast, downregulation of either PKC epsilon or PKC alpha reduced
      immunoreactivity towards the phosphate-independent anti-tau antibodies 5E2 and
      JM, suggesting that both of these isoforms participated in regulation of tau
      steady-state levels. Downregulation of PKC beta did not affect any of the above
      changes. The above roles were apparently unique for PKC epsilon and PKC alpha,
      since activation of multiple PKC isoforms by phorbol ester treatment and/or other
      calcium-dependent kinase(s) by ionophore-mediated calcium influx could not
      compensate for downregulation of PKC alpha or PKC epsilon in maintaining tau
      steady-state levels or PHF-I/ALZ-50 immunoreactivity, respectively. These
      findings suggest that hyperactivation of signal transduction pathways, including
      those regulated by PKC, could evoke changes in neuronal cells reminiscent of
      those seen in affected neurons in Alzheimer's disease.

PMID- 9253655
TI  - Induction of cyclic AMP and cyclic GMP 3':5'-cyclic nucleotide phosphodiesterase
      activities in neuroblastoma lines under differentiating conditions.
AB  - It is now widely accepted that cyclic nucleotide phosphodiesterases (PDEs) play
      fundamental roles in signal transduction pathways; they show a remarkable
      molecular complexity, different tissue distribution and complex regulatory
      mechanisms. Here we report PDE isoforms expression in two dibutyryl cyclic AMP
      differentiated murine cell lines: the hybrid neuroblastoma-glioma 108CC15 and the
      parental neuroblastoma N18TG2. They differ in the ability to establish functional
      synapses, a feature present only in the former. Ionic exchange chromatography
      elution profiles of N18TG2 and 108CC15 undifferentiated cell extracts show two
      main peaks of activity. The first one hydrolyzes cyclic GMP and is specifically
      inhibited by Zaprinast, thus representing a member of the PDE5 family. The second
      peak hydrolyzes cyclic AMP and is significantly inhibited by rolipram, as all the
      PDE4 family members. The induction of differentiation by dibutyryl cyclic AMP in
      both clonal lines results in an increase of PDE activities only after 3 hr of
      treatment, suggesting that protein neosynthesis is involved. Interestingly in
      both clones, besides the increase in cyclic AMP hydrolyzing specific activity
      (3.1-fold in 108CC15 and 2.5-fold in N18TG2), we also observed an increase in
      cyclic GMP hydrolyzing activity (1.7-fold in 108CC15 and 4.3-fold in N18TG2).
      While the induction of PDE4, previously reported also in other cellular systems,
      could be considered as a feedback response to the higher cyclic AMP levels, this
      is not true for the isoform that hydrolyzes cyclic GMP. These data suggest that
      the induction of PDE isoforms in neuroblastoma cells could be related to the
      activation of neuronal differentiative pathway.

PMID- 9253656
TI  - Lead-induced developmental changes in AP-1 DNA binding in rat brain.
AB  - Exposure to lead during ontogeny is detrimental to the growth and development of
      the brain. Morphological abnormalities occur in the developing brain, which are
      manifested as mental retardation and other neurological disorders. Despite
      extensive research, the biochemical mechanism for neurological effects of lead
      has not been established but appears to be at the level of the genome since
      aberrant expression of developmentally-important genes has been reported. Basal
      levels of activator protein 1 (AP-1) transcription factor DNA binding are
      elevated in the rat brain during the early postnatal period. The AP-1 DNA binding
      complex is composed of a Jun:cAMP responsive element binding protein dimer, which
      appears to modulate expression of developmentally-important genes that contain AP
      1 binding sites in their promoter. Brain regions from perinatally lead-exposed
      rats were examined on postnatal days 3, 9 and 15 for DNA binding activity to the
      AP-1 DNA sequence. AP-1 DNA binding activities were significantly increased on
      postnatal day 3 in hippocampus and cortex from lead-treated rats with no other
      area (frontal lobe or brainstem) or timepoint showing significant changes. Since
      no increases were detected in the level of Jun protein which is a component of
      the AP-1 binding complex, post-translational modification may be involved in
      enhancing DNA binding activity. By altering levels of AP-1 DNA binding to the
      promoter regions, lead exposure may be changing the levels of mRNA synthesis of
      developmentally important genes.

PMID- 9253657
TI  - G-protein expression in melanotropes changes coincident with innervation of the
      developing rat pituitary intermediate lobe.
AB  - The two isoforms of the dopamine D2 receptor, the D2short and the D2long differ
      in a 29 amino acid insert in the third cytoplasmic loop with which G proteins
      interact. We have previously reported that in rat melanotropes, expression of
      D2short increases markedly at the end of the first postnatal week which is
      concurrent with innervation of the intermediate lobe. Using immunohistochemistry,
      this study examined expression of G alpha i1/2, G alpha i3, G alpha o and G alpha
      s proteins before and after dopaminergic innervation. G alpha i3 increased
      through gestational day 20, and then remained level to postnatal day 6. At this
      time, coinciding with the induction of D2short expression, G alpha i3
      immunoreactive intensity increased markedly, possibly indicating co-regulation of
      these proteins. On postnatal day 6, G alpha s immunoreactive intensity increased
      in some, but not all, melanotropes. The resulting heterogeneity in Gs expression
      persisted in the adult. G alpha i1/2 immunoreactivity did not change and G alpha
      o was detected only subsequent to the event of innervation. Thus, dopamine
      released from axons and acting through D2 receptor stimulation could increase G
      alpha i3 immunoreactivity and decrease G alpha s immunoreactive intensity in some
      melanotropes.

PMID- 9253658
TI  - Lack of biocytin transfer at gap junctions in the chicken vestibular nuclei.
AB  - In vivo experiments were designed to test for functional gap junctions at 'mixed'
      synapses that were morphologically characterized between the large-diameter,
      primary vestibular fibers and second-order vestibular neurons in the chicken,
      Gallus gallus. In previous intracellular recordings and dye injections into these
      neurons from brain slice preparations of chick embryos (E15/16) and also newborn
      hatchlings (HI-2), no evidence was obtained for functional gap junctions.
      Therefore, biocytin, a low molecular weight tracer that permeates gap junction
      channels, was extracellularly applied to either the ampullary nerves or to the
      vestibular ganglion of 3-6 day old hatchlings and adult chickens (9 months). This
      procedure resulted in the uptake of the dye and heavy staining of both the thick
      and thin fibers composing the vestibular nerve and in loading of vestibular
      efferent neurons. However, no dye transfer was observed between the large
      diameter, primary vestibular fibers and second-order vestibular neurons. This
      observation, which was performed using a relatively non-invasive approach on
      intact animals, suggests that the gap junctions at these mixed synapses are
      probably not functional under the conditions of these experiments.

PMID- 9253659
TI  - Neurochemical coding in the myenteric plexus of the upper gastrointestinal tract
      of hibernating hamsters.
AB  - As part of our investigation of the plasticity of autonomic nerves in
      physiological and pathological conditions, we have examined the effect of
      hibernation on the neurochemical content of myenteric nerves and nerve cell
      bodies of the upper gastrointestinal tract of the non-seasonal hibernator, the
      golden hamster. Age matched hamsters kept at room temperature and those kept at 5
      degrees C but which failed to hibernate, were used as controls. Possible changes
      in nerve fibres and nerve cell bodies containing the general neuronal marker,
      protein gene product 9.5, the peptides, vasoactive intestinal polypeptide,
      substance P (SP) and calcitonin gene-related peptide (CGRP), the catecholamine
      synthesizing enzyme tyrosine hydroxylase and the enzyme responsible for
      synthesizing nitric oxide, nitric oxide synthase, were examined in the
      oesophagus, proventriculus and proximal and distal stomach of the golden hamsters
      using immunohistochemical techniques. The results of the present study revealed a
      significant increase in the number of nerve cell bodies and density of nerve
      fibres containing SP-immunoreactivity and increased number of CGRP-immunoreactive
      cell bodies but not the other markers examined in the proximal stomach and
      proventriculus. In contrast, there was no change in the distribution of any of
      the neuroactive substances examined in the myenteric plexus of the oesophagus and
      distal stomach. It is suggested that the change in the environment of the
      hibernating hamsters perturbs the normal digestive physiology in the proximal
      stomach and proventriculus that is reflected by the selective changes in SP- and
      CGRP-containing enteric nerves; these changes may be part of protective reflex
      mechanisms to the environmental changes resulting from hibernation, where
      upgrading of nerve cell bodies expressing CGRP and SP has occurred.

PMID- 9253660
TI  - Development and maturation of noradrenaline-containing nerves of the rat uterine
      artery. Effects of acute and chronic oestrogen treatment.
AB  - The development and maturation of noradrenaline-containing nerves of the rat
      uterine artery was investigated, histochemically and biochemically, at seven
      different postnatal age-stages and following acute and chronic treatment with
      oestradiol. Morphological changes in the vessel were quantitatively evaluated on
      Toluidine Blue-stained semithin sections and low magnification
      electronmicrographs. In summary, the uterine artery is innervated at birth; the
      adult pattern of innervation is established at two weeks of age; the innervation
      density increases progressively between the infantile and prepubertal periods,
      accompanying proliferation and growth of smooth muscle cells in the tunica media;
      changes in the innervation are followed by an increase in the tissue
      concentration of noradrenaline and neither the endocrine changes characterizing
      puberty nor acute or chronic treatment with oestradiol have an effect on the
      pattern of development of the uterine artery and associated noradrenaline
      containing nerves. Results are interpreted considering the differential
      susceptibility of urinogenital organs to sex hormones.

PMID- 9253661
TI  - Global trends in women's health.
AB  - Global trends in women's health have to be looked at in the broader context of
      the definition of health as a state of complete physical, mental and social well
      being, and not merely the absence of disease or infirmity. Our species is
      undergoing a historical bio-social evolution, with women positioned to have more
      power over their bodies and their lives. The implications for women's health are
      vast. Our profession has to face new challenges. The woman behind the mother is
      finally emerging, and making her presence felt. A reproductive evolution is
      sweeping the globe, with women having to lead a contraceptive life. A
      contraceptive technology revolution has benefited hundreds of millions, but the
      task is still unfinished. Demand for quality is substituting a desire for
      quantity in human reproduction. Sexual health is becoming an important
      psychosocial component of our health and well-being. The mature adult woman and
      the elderly woman are rising to an important place in our health care. The
      widening bio-social gap in adolescents dictates an increasing need for
      appropriate promotive, preventive and curative health care. One global trend in
      women's health unfortunately did not happen. Maternity is still, unnecessarily, a
      major cause of death and morbidity for women in developing countries.

PMID- 9253662
TI  - Women's health problems in the Arab World: a holistic policy perspective.
AB  - The paper reviews key health problems of women in the Arab World. It relies on
      data and information from international yearbooks, regional data bases, and small
      scale field studies. The relevant context in which women live; of lingering
      illiteracy rates, lack of access to cash income, and increasing poverty is
      described. Reproductive health is reviewed within this context pointing to trends
      of delayed marriage and declining fertility in some countries while other
      countries maintain high levels. Similar variability is observed in contraceptive
      use rates and the interaction of contraception and health is discussed. Evidence
      points to high levels of reproductive morbidity. The socio-cultural context is
      found particularly relevant to pregnancy and childbirth, seen as natural
      processes by women, to experiences of menopause, and to violence against women,
      particularly female circumcision. A holistic policy perspective is suggested to
      address these problems.

PMID- 9253663
TI  - The effect of women's role on health: the paradox.
AB  - Most societies in Africa are patriarchal in nature. Traditional Africa has
      allocated the role of nurturing, and ensuring the health of the family and the
      community as a whole to women. From the age of six, girls begin to work with
      their mothers, cleaning, sweeping, nursing and caring for the younger children,
      the aged and the sick. Therefore, the female child is customarily socialized as
      the custodian of family health. Because women are traditionally responsible for
      health in African countries and their status in society is low, the status of the
      health sector has received less attention than other sectors. The paradox of
      entrusting the woman with the responsibility of health and at the same time
      denying her the opportunities to influence policies remains a major obstacle.
      Factors that influence women's health in Africa most commonly include poverty,
      poor education and poor nutrition. Access to education for African women is a
      major problem. The impact of a poorly educated mother is passed on to the
      daughter. In some parts of Africa, female circumcision contributes to the high
      school dropout rates. Once the girls are withdrawn from school to participate in
      the ceremonies, they do not return to school. They are encouraged and socialized
      towards marriage. Africa has the highest fertility rate, the lowest life
      expectancy (49 years for males and 52 for females, the highest infant mortality
      rate (114 deaths per 1000 live births); the highest maternal mortality rate and
      the highest dependency ratio (47% under 15 years and only 3% over 65). The
      foregoing factors call for urgent attention to health issues, especially those
      which affect women who are the traditional health providers. There is an
      unacceptably high rate of unsafe abortion which accounts for up to 30% of
      maternal mortality in some African countries, and there is growing concern over
      teenage pregnancies in some African countries. Nearly two-thirds of the cases of
      septic abortions are in the 15-19-year age group and yet African governments and
      the legal systems would rather not deal with abortion. The gap between mortality
      and fertility is widening; it doubled between 1972 and 1994 and is expected to
      double in 2017. In many African countries, children are the only 'goods' that
      women are expected to produce. Unless this attitude changes, fertility rates will
      continue to rise as women continue to search for their place in society and
      justify their place within marriages and relationships through child bearing.

PMID- 9253664
TI  - Impact of roles of women on health in India.
AB  - India's population has more than doubled since 1961. Although India has been a
      leader in developing health and population policies, there have been major
      implementation problems due to poverty, gender discrimination, and illiteracy.
      Yet, three-quarters of the food produced annually in India is because of women.
      In 1991, only 39.3% of Indian women were literate. The literacy level of women
      can affect reproductive behavior, use of contraceptives, health and upbringing of
      children, proper hygienic practises, access to jobs and the overall status of
      women in the society. Early marriage and childbirth was a major determinant of
      women's health and was also responsible for the prevailing socioeconomic
      underdevelopment in India. The overall maternal mortality for India is 572.3 per
      100,000 births, ranging from 14.9% in Bihar to 1.3% in Kerala. Anemia is an
      indirect factor in 64.4% of the maternal deaths. Trained birth attendants
      currently assist in about 60-80% of all births in women at the time of delivery.
      Socioeconomic factors are responsible for maternal deaths to a large extent -
      money in 18.3%, transport in 13.7%. When the mother dies it doubles the chances
      of death of her surviving sons and quadruples that of her daughters. Among the
      avoidable factors in maternal deaths, lack of antenatal care is the most
      important. Women, if educated and aware, can improve the health of their children
      by simple measures like good hygiene, exercise and dietary habits. Because of
      poverty, many of the young children, especially girls living on streets are easy
      prey for criminal prostitution rings, drug trafficking and consequences of HIV
      infection, and severe emotional and mental disturbances. Women are responsible
      for 70-80% of all the healthcare provided in India. Female healthcare providers
      can play an important role in educating society to recognize their health and
      nutrition needs. Women professionals and empowerment of women at all levels are
      required for improvement of the health and nutrition structure in India.

PMID- 9253665
TI  - The American College of Obstetricians and Gynecologists: a decade of responding
      to violence against women.
AB  - Violence against women is a common phenomenon worldwide. Effects can be severe
      and life-long. As physicians who treat women exclusively, the obstetrician
      gynecologist has a medical and ethical obligation to recognize and intervene on
      behalf of their abused patients. At the same time, because of the special nature
      of the patient-physician relationship, the obstetrician-gynecologist is in a
      unique position to provide such assistance. This article presents an overview of
      violence against women and its consequences, highlights responses to the problem,
      and details the activities of the American College of Obstetricians and
      Gynecologists to educate its members on domestic violence. ACOG activities may
      serve as a model of response to domestic violence for similar organizations.

PMID- 9253666
TI  - Family planning in Russia.
AB  - The data concerning the abortion rate in Russia for the past 5 years are
      presented. They demonstrate that abortion has been the main means of birth
      control. At present, the government, the Ministry of Public Health, obstetricians
      and gynecologists, and public organizations are making every effort to introduce
      medical and non-medical means of contraception.

PMID- 9253667
TI  - Current practice of family planning in China.
AB  - Current practice of family planning in China is based on the population policy
      and strategy of the country. Comprehensive contraceptive methods are provided in
      family planning clinics at all levels. Among the methods used, intrauterine
      devices and tubal sterilization are most popular. Vasectomy is popular in some
      provinces. Oral pills, injectables and subdermal implants occupy a small
      proportion. Incidence of abortion is high due to failure of methods and
      unprotected intercourse. Attention is paid to the adoption of emergency
      contraception to prevent unwanted pregnancy. Improvement in quality of care is
      the key to a successful family planning program. Basic research is essential for
      development of new contraceptive technology.

PMID- 9253668
TI  - Abortion and contraceptive practices in eastern Europe.
AB  - In countries of the CCEE region (Countries of Central and Eastern Europe) the
      very high incidence of pregnancy termination is characteristic of family planning
      and the notion 'contraception instead of abortion' has not yet been achieved. The
      causes and consequences of this unfortunate situation will be reviewed: the
      reproductive health indicators in the area; the status of contraceptive use and
      of abortion; the impact of legislation in the different countries; and the
      efforts to achieve changes. The conclusions of the 'Szeged Declaration' which led
      to an increase in contraceptive prevalence will be discussed.

PMID- 9253669
TI  - Illegal abortion: consequences for women's health and the health care system.
AB  - Illegal abortion is responsible for up to half of maternal deaths and consumes a
      large proportion of health resources in many developing countries, particularly
      in Africa and Latin America. The legal situation of abortion in a country does
      not influence the abortion rate, but illegality is associated with a much greater
      risk of complications and death. To make abortion legal is not enough. Access to
      safe abortion strongly depends on the capacity and willingness of physicians and
      the health system to provide safe services, which sometimes are made available in
      spite of restrictive laws. The abortion rate will drop and the safety of the
      procedure will improve, parallel to the position women occupy in a given society,
      and to the level of recognition of their sexual and reproductive rights. The
      medical profession, and FIGO in particular, has a great role to play in
      implementing initiatives that will reduce the consequences of illegal abortion
      for women and society.

PMID- 9253670
TI  - Improving adolescent sexual behavior: a tool for better fertility outcome and
      safe motherhood.
AB  - The consequences of increased adolescent sexuality worldwide include: an
      increased rate of adolescent pregnancies and abortions; a high prevalence of
      sexually transmitted diseases; and a significant number of psychosocial problems.
      Improvement of adolescent sexual behavior should be one of the primary goals of
      the 21st century. This includes development of new contraception techniques,
      providing protection from sexually transmitted diseases, improvement of
      contraception compliance and the correct use of mass media. As adolescents seek
      advice on sexual matters, it is our responsibility to provide them with accurate
      consultation as well as free family planning services in well organized
      adolescent units, where they may be counselled on the prevention of unwanted
      pregnancy, and sexually transmitted diseases. This will assist in a better
      fertility outcome and a safe motherhood.

PMID- 9253671
TI  - Family planning in the 21st century: perspective of the International Planned
      Parenthood Federation.
AB  - Many women still die as a result of pregnancy or childbirth and yet there are an
      increasing number of women who wish to regulate their fertility and space or
      limit their child-bearing. This paper, outlining some success stories, elucidates
      the family planning challenges and identifies key messages to indicate the role
      that IPPF can play in the 21st century. Issues such as advocacy for sexual and
      reproductive health and rights, increased male participation, serving the
      interests of marginalized groups, appropriate technology, quality of care and
      cooperation between various partners, all need to be addressed to improve sexual
      and reproductive health including family planning in the 21st century.

PMID- 9253672
TI  - Implementing family planning programs in developing countries: lessons and
      reflections from four decades of Population Council experience.
AB  - Over the last three decades, contraceptive prevalence has risen from about 10% to
      nearly 60% in developing countries, but still about 1 in 4 births in developing
      countries (outside China) is unwanted. More than 120 million women in these
      countries who do not want to become pregnant do not use contraceptives. Nearly
      600,000 women die each year from pregnancy-related causes, between 67,000 and
      204,000 of them from unsafe abortions. At the 1994 International Conference on
      Population and Development in Cairo, delegates endorsed the view long advocated
      by the Population Council: the primary purpose of family planning programs should
      be to help women avoid unwanted pregnancy and achieve their fertility goals
      safely. That means, at the very least, that programs should address those
      reproductive health issues that are directly related to fertility regulation. To
      meet the Cairo challenge, progress is needed simultaneously on several levels. We
      need more and better contraceptive technologies that meet the needs of different
      groups; higher-quality family planning services; more outreach to underserved
      groups (such as men and adolescents); programs tailored to local cultures; and
      measures to address all the factors that prevent women who do not want to become
      pregnant from using contraceptives. The call for a client-centered, reproductive
      health approach to family planning constitutes a critique of programs driven by
      demographic goals. The new family planning paradigm puts a premium on 'quality of
      care'. Unfortunately, many family planning programs still fall substantially
      short of offering clients reproductive choice and supporting their reproductive
      health. The Population Council takes the view that contraceptive research and
      development is an essential component of a multilevel strategy to reduce unwanted
      fertility safely. New products, used ethically and provided with quality, would
      be of tremendous benefit to women and men throughout the world. The Population
      Council has developed, registered, and licensed seven products, including some of
      the most widely used contraceptives in the world. The Council is also one of the
      world centers for research on male reproductive physiology and male
      contraception. New contraceptive methods are only as good as the context in which
      they are offered. To accelerate the pace of overall fertility decline,
      governments must adopt policies that reduce the economic and social risks
      associated with having smaller families, and policies that promote later and
      planned childbearing.

PMID- 9253673
TI  - Sexually transmitted diseases: global importance.
AB  - The worldwide incidence of sexually transmitted diseases (STDs) including the
      human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)
      continues to increase and represents a major public health problem especially in
      the developing world causing infertility and ectopic pregnancy. Prevention of the
      spread of STDs, along with early detection and appropriate therapy has the
      potential to minimize the reproductive tract damage of these infections and
      simultaneously improve the health of women in all areas of the world.

PMID- 9253674
TI  - HIV and women in Thailand: severity and services.
AB  - Thailand has extensive data on the emergence of HIV and aggressive prevention
      programs to prevent the spread of the disease. The increasing HIV infection among
      women who desire pregnancy increases the number of HIV-infected infants. Standard
      guidelines for HIV testing include that the test should be voluntary, counseling
      should be given before and after testing, the test results should be kept
      strictly confidential, AIDS education should be provided for all hospital
      personnel, and an appropriate hospital policy on AIDS is in place. In HIV
      positive women decisions about pregnancy termination or continuation is usually
      made by both husband and wife after counseling about the possibility of perinatal
      transmission. The current practices in Thailand of patient care, antenatal care,
      management of labor, breast feeding and contraceptive practice are reviewed.

PMID- 9253675
TI  - Effects of chronic parasitosis on women's health.
AB  - Parasitic diseases are closely related to the lack of sanitation (unavailability
      of potable water, inadequate disposal of human waste, lack of latrines) or the
      absence of personal hygiene. They are also closely linked to warm and humid
      climates, and are therefore considered tropical diseases. This chapter addresses
      chronic hookworm parasitosis and malaria, and their effect on women's health. Of
      all Helminthes, hookworms cause the most severe anemia because of iron deficiency
      due to chronic blood loss. Worldwide, an estimated 51% of pregnant women suffer
      from anemia-almost twice as many as non-pregnant women. In severe cases (Hb < 70
      g/l) the risk of perinatal maternal and child death increases up to 500-fold.
      Anemia due to maternal deficiency affects the fetus, causes retarded intrauterine
      growth, and reduces fetal ability to absorb iron provided by the mother.
      Hookworms are nematodes that infect roughly 1 billion people. Their preferred
      habitat is the jejunum, where they attach to the mucous tissue to feed, and
      secrete an anticoagulant causing bleeding. Hookworm infections often begin in
      childhood. The worm enters the body through the skin and reaches the highest
      number at the end of adolescence and young adulthood. Little attention has been
      given to the treatment of pregnant women because of unavailability of safe
      antiparasitic drugs and fear of teratogenesis. However, there are new treatments,
      and the anthelminthic drugs may be administered in schools and organized women's
      groups in communities. During pregnancy anthelminthic treatment can improve
      maternal, fetal and infant health. Treatment given every 4 months has been shown
      to interrupt the transmission cycle of the parasite and help to improve the iron
      status of all women. Therapeutic strategies should be linked to other measures,
      such as promoting the use of shoes, introduction of potable water, education and
      treatment of the population at large, especially the school-age population. An
      estimated 267 million people are annually infected by malaria, a parasitic
      disease caused by Protozoa of the genus Plasmodium. Malaria is transmitted by the
      Anopheles mosquito and is highly prevalent in tropical and subtropical regions
      located between 40 degrees latitude North and 30 degrees latitude South. It
      causes acute attacks that leave the human body in such a poor state that health
      problems resulting from these attacks become chronic. Due to the high mortality
      and morbidity associated with it, malaria is considered the most serious of
      tropical diseases and a major public-health dilemma. Pregnant women are at high
      risk of becoming infected, as well as children in their first years of life. In
      pregnant women, malaria can cause anemia which can be the major cause of maternal
      mortality, especially during the first pregnancy. Malaria can also cause fetal
      anemia which frequently results in retarded intrauterine growth and low birth
      weight. Prophylactic treatment with antimalarial drugs during pregnancy is
      recommended in areas where the disease is endemic. The prophylactic treatment
      should focus primarily on primiparous women who are most susceptible. Chloroquine
      is safe and effective for antimalarial prophylaxis, and is not teratogenic.
      Proguanil is also safe for prophylactic use during pregnancy, particularly in
      areas where P. falciparum is resistant to chloroquine. Mefloquine may be used
      during the third trimester of pregnancy, only if other antimalarial drugs are
      unavailable or ineffective.

PMID- 9253676
TI  - Impact of cancer screening on women's health.
AB  - Worldwide, 31% of cancers in women are in the breast or uterine cervix.
      Prevention of cervical cancer is effective with the use of the cervical Pap smear
      test if applied in an organized and continuous fashion, including treatment of
      precancerous lesions. At best such programs have led to a 60% decrease in
      cervical cancer incidence and mortality in the Nordic countries. Early detection
      of breast cancer in a population based screening may lead to a 30% reduction of
      mortality from this disease in the screened population. Measures to guarantee
      high coverage and attendance, adequate field facilities, organized program for
      quality control and adequate facilities for diagnosis and treatment are
      prerequisites of successful programs. In absolute terms the contribution of
      screening to the total mortality reduction among middle-aged populations is
      small, much smaller than the potential gains from cancer prevention.

PMID- 9253677
TI  - Global importance of infertility and its treatment: role of fertility
      technologies.
AB  - Understanding the reasons for infertility and the development of new techniques
      for its treatment is one of the fields within medicine which has undergone a
      dramatic development during the last two decades. In the past, gynecologists
      seemed more successful in the treatment of female problems than urologists and
      andrologists on the male side, while in the last couple of years this scenario
      has changed due to the development of both operative procedures to harvest
      spermatozoa from the epididymis and the testis and the ability to micro-inject
      single spermatozoa (ICSI) or even spermatides directly into metaphase II oocytes.
      It should, however, be emphasized that the successful development of in vitro
      fertilization (IVF) and other assisted reproduction technologies (ART), could not
      have taken place without the development of diagnostic innovations, such as
      immunoassays of hormones, high resolution ultrasound and various endoscopic
      techniques. Today, treatment of the infertile couple is less of a medico
      technical problem and more a socio-economic dilemma. This communication is an
      attempt to summarize the more prominent steps in reproductive medicine during the
      last decades and one more general conclusion of global relevance which can be
      drawn, is that less money must be spent on diagnosis and more resources
      transferred to treatment options.

PMID- 9253678
TI  - Inappropriate use of new technology: impact on women's health.
AB  - While medical technology is very useful we need to be aware of its inappropriate
      use. Examples are given, such as: continuous vs. intermittent electronic fetal
      monitoring; widespread use of magnetic resonance image technology where simple
      methods could be as effective; laparoscopically assisted vaginal hysterectomies
      replacing simple vaginal hysterectomies and increasing the cost; ultrasound to
      provide the first pictures of the baby or to detect female fetuses for female
      feticide; use of technology for defensive medicine rather than using it for the
      patient's welfare, and pecuniary indications. Woe betide the doctor who does not
      make enough money--he may find that his contract is not renewed. We need to
      empower patients with information, so that they can judge the technology and its
      appropriateness as it relates to them. Opinion programs have helped to curb the
      misuse of unnecessary surgery, and audit and peer review programs also provide a
      check on the misuse of technology. The provision of consensus statements, e.g. by
      the National Institutes of Health, USA, have helped to clarify issues and to
      guide doctors as to the appropriateness of the newer technologies, and practice
      guidelines formulated by experts are also very helpful. We need to teach medical
      students and residents how to be critical, how to evaluate claims and study the
      literature, so that they are not hoodwinked by 'authority' or misled by
      manufacturer's claims.

PMID- 9253679
TI  - Ethical issues relating to reproduction control and women's health.
AB  - There are many ethical aspects which derive from the application of reproduction
      control in women's health. Women's health can be enhanced if women are given the
      opportunity to make their own reproduction choices about sex, contraception,
      abortion and application of reproductive technologies. The main issues that raise
      ethical dilemmas following the development of assisted reproduction techniques
      are: the right to procreate or reproduce; the process of in vitro fertilization
      itself-is it morally acceptable to interfere in the reproduction process?; the
      moral status of the embryo; the involvement of a third party in the reproductive
      process by genetic material donation; the practice of surrogacy, cryopreservation
      of pre-embryos; genetic manipulation; experiments on pre-embryos, etc. Induced
      abortion raises ethical issues related to the rights of the woman versus the
      rights of the fetus. For those who consider life to begin at conception abortion
      always equals murder and is therefore forbidden. Those who believe in the
      absolute autonomy of the woman over her body take the other extreme approach. The
      discussion surrounding abortion usually centers on whether it should be legal or
      illegal. Access to safe abortion is critical to the health of women and to their
      autonomy. The development of new effective contraceptive methods has a profound
      impact on women's lives. By the use of contraception it is possible to lessen
      maternal, infant and child mortality and to reduce the prevalence of sexually
      transmitted diseases. Research and development of new effective reversible
      contraceptives for women and men is needed. Dissemination of information about
      the safety and effectiveness of contraceptive methods is of great importance.
      Female genital mutilation is still practiced worldwide due to customs and
      tradition among various ethnic groups. The procedure is considered to be
      medically detrimental to the physical and mental health of women and girls, and
      is considered by many as oppression of women. The practice has to be stopped.
      Recognition of the fetus as a 'patient' has a potential effect on women's right
      for autonomy; they have no legal obligation to undergo invasive procedures and to
      risk their health for the sake of their fetuses. The woman carries ethical
      obligations toward her fetus. This obligation should not be enforced by the law.
      At present women bear most of the burden of reproductive health. All of them have
      a right of access to fertility regulation. Governments and society must ensure
      the women's equal rights to health care just as men have in the regulation of
      their fertility.

PMID- 9253680
TI  - Women and the third and fourth age.
AB  - In 1900, the world population was less than 1.7 billion people; the United
      Nations projects that in 2000 it will be 6.2, and in 2020, 7.9 billion. The
      proportion of the elderly (65 years and over), will increase from 5.1% (1950) to
      6.8% by the year 2000 and to 8.8% by 2020, when out of an elderly population of
      796 million people, 124 million are projected to be 80 years and over. Due to an
      increasing gender inequality in life expectation, the majority of the elderly
      will be women. An aged population is a basically new feature in the history of
      humanity, the implications of which are-as yet-incompletely understood. It is
      clear, however, that the last years of life are accompanied by an increase in
      disability and sickness, with very high demands for health and social services.
      Hence, the soaring elderly population will raise major social, economic and
      ethical issues worldwide and may strain to the limit the ability of health,
      social and economic infrastructures of many countries. It may also result in an
      increasingly large proportion of humanity (the elderly in general and elderly
      women, in particular) living in absolute poverty. The demographic, health,
      socioeconomic and ethical dimensions of the problem are discussed with particular
      emphasis on the situation of elderly women and a plea is made for greatly
      increased medical and socioeconomic research.

PMID- 9253681
TI  - Skin microcirculation responses to severe local cooling.
AB  - When skin is exposed to cold, cutaneous blood flow is initially restricted due to
      sympathetic vasoconstriction. Prolonged exposure to cold has a secondary
      protective vasodilator effect. In the present study, the effects of severe and
      prolonged local cold on the cutaneous microcirculation were assessed. In 10 young
      healthy subjects, laser Doppler skin flux and flux motion were measured at the
      calf during 20 min of local ice cooling and 15 min subsequent recovery. In the
      6th minute of cooling, mean skin flux decreased to 58 +/- 6% of the resting value
      (p < 0.05), then increased and reached 129 +/- 10% of the resting value at the
      end of the cooling period, followed by a phase of reactive hyperemia with a
      maximum of 225 +/- 24% (p < 0.05). Mean flux motion frequency, spontaneously
      present at rest with a frequency of 2.6 +/- 0.2 cycles/ min decreased rapidly
      during the first minutes of cold exposure, was absent during the 6th to the 10th
      minute, reappeared and started to increase from the 11th minute and reached 4.4
      +/- 0.3 cycles/min during the recovery period (p < 0.05). This study seems to
      indicate that the phenomenon of protective increase of cutaneous microcirculatory
      blood flow consists of an initial phase of vasodilation, followed by a phase of
      active and enhanced microvessel vasomotor activity.

PMID- 9253682
TI  - Effect of Ginkgo biloba extract (EGb 761) on the vasospastic response of mouse
      cutaneous arterioles to platelet activation.
AB  - The effect of intravenously administered Ginkbo biloba extract (EGb 761) on the
      vasospastic response to platelet activation has been assessed using a cutaneous
      flap preparation in anaesthetized mice. Arterioles of the axillary artery were
      observed by intravital microscopy, and platelets were activated by topical
      application of ADP under two steady state conditions: normothermia (37 degrees C)
      and hypothermia (24 degrees C). Responses of the cutaneous arterioles to
      stimulation by topical application of a thromboxane agonist (U46619) were also
      compared in animals treated intravenously with EGb 761 or with a thromboxane
      synthesis inhibitor (U63557). ADP induced a 34% constriction of the arterioles in
      control animals. However, no arteriolar constriction occurred in response to ADP
      in platelet-depleted animals (collagen-induced thrombocytopenia) or in animals
      treated with EGb 761 (60 mg/kg, i.v.). Exposure of the arterioles to hypothermia
      (24 degrees C) for 10 min induced constriction of 7-12% in all experimental
      groups of animals. Under these hypothermic conditions, either EGb 761 or
      thrombocytopenia abolished ADP-induced arteriolar constriction which was
      substituted by arteriolar dilation, indicating that EGb 761 can inhibit the
      vasospasm that is produced by platelet activation. As topically applied U46619
      (10(-5) M) induced arterioles constriction (about 22%) that was abolished by
      intravenous treatment with EGb 761, the extract appears to act directly rather
      than as a thromboxane synthase inhibitor. Collectively, these findings indicate
      that platelet factors can play a significant role in cutaneous vasospasm, and
      that EGb 761, via an action on the thromboxane pathway, could be useful in
      treating Raynaud's phenomenon and other vascular disorders which involve
      increased thromboxane production.

PMID- 9253683
TI  - The influence of cellular hypoxia and reactive oxygen species on the development
      of endothelial cell edema.
AB  - We investigated in vitro whether endothelial cell edema is induced by cellular
      hypoxia or oxygen radical formation. Measurements of relative cell volume (RCV)
      were made using microweight analysis, liquid scintillation spectrometry and
      analysis of cellular protein content. To validate this method of determining cell
      volume, endothelial cells were incubated in media of different osmolarities.
      Vascular endothelial cells reacted to osmotic stress with a volume increase or
      decrease. The addition of xanthine oxidase (XOD; 3 mU/ml) and hypoxanthine (1 mM)
      for the enzymatic production of O2- caused a reproducible and significant
      increase in RCV by 29 +/- 8% (from 5.5 to 7.1 microliters/10(6) cells; p < 0.001)
      after an incubation time of 60 min. Nonenzymatically produced H2O2 (100 microM)
      caused a similar increase in RCV by 35 +/- 5% (from 5.5 to 7.6 microliters/10(6)
      cells; p < 0.001) over the same incubation period. The addition of catalase (50
      U/ml) diminished the increasing effect of XOD as well as that of H2O2 on cell
      volume. As assessed by the uptake of the vital dye trypan blue and the release of
      lactate dehydrogenase into the medium, there was no significant loss of viability
      during the incubation time. Lower concentrations of H2O2 as well as lower
      activities of XOD did not induce a significant increase in RCV. Higher H2O2
      concentrations and increased XOD activities caused a considerable time- and
      concentration-dependent injury of endothelial cells. RCV was unchanged even after
      long exposure (5 h) to two different hypoxic gas mixtures (3% O2:5% CO2:92% N2;
      0% O2:5% CO2:95% N2). Cell viability was not impaired under hypoxic conditions.
      The results suggest that reactive oxygen species play a more important role in
      the development of endothelial cell edema than cellular hypoxia.

PMID- 9253684
TI  - Microvascular permselectivity in the chick chorioallantoic membrane during
      endothelial cell senescence.
AB  - The chorioallantoic membrane (CAM) of the chick embryo represents an in vivo
      model to evaluate microvascular function during the sequential phases of
      endothelial proliferation (angiogenesis), cytodifferentiation, and senescence.
      The principal focus of this study was to characterize microvascular barrier
      functions of the CAM endothelium during its nonproliferating, aging phase
      (senescence). A graded series of fluorescein isothiocyanate (FITC) dextrans
      served to index macromolecular selectivity of the senescent capillary
      endothelium. Extravasation of FITC dextrans 40 and 150 was restricted, while FITC
      dextran 10 progressively accumulated within the intercapillary interstitia during
      15-min perfusion periods. Endothelial vesicle densities were greater in the first
      and second-order pre- and first- order postcapillary endothelia (28 +/-
      8/micron2) than those recorded for the capillary endothelium (8 +/- 3/micron2).
      Junctional cleft lengths (luminal to abluminal distances), on the other hand,
      were greater in the capillary endothelium (1.08 +/- 0.50 microns) than those
      recorded for the second-order pre- and postcapillaries (0.46 +/- 0.03 micron).
      Junctional cleft widths were segmentally uniform (20 nm) in the microvascular
      units. That permselectivity of the segmental microvascular endothelia was
      homogeneous is ultrastructurally consistent with the uniform junctional cleft
      widths rather than the heterogeneous cleft lengths and vesicle densities. The CAM
      serves as the principal respiratory exchange surface of the embryo. Thus,
      maintenance of colloid oncotic balance across the microvascular endothelium is
      likely critical to gaseous exchange. The retention of a selective barrier during
      the senescent phase of the CAM endothelium serves to support this concept.

PMID- 9253685
TI  - Skin blood flow during vasoconstrictive and vasodilative stimuli in essential
      hypertension patients: a laser Doppler flowmetry study.
AB  - In order to compare the extent of the elicited vasoconstrictive and vasodilative
      response at the microcirculatory level in essential hypertension (EH), we
      measured the skin blood flow by means of a laser Doppler flowmeter (LDF). Thirty
      four mild-to-moderate EH patients were enrolled. Twenty-two sex- and age-matched
      healthy subjects were selected as a control group. The LDF measurements were
      carried out with the probe over the fingertip of the distal phalanx at baseline
      conditions (Rest flow, RF), after an ischaemic test (post-ischaemic peak flow)
      and during an arithmetic stress test (AT). The flow was expressed in arbitrary
      units. The data were processed using the Perisoft computer program. The relative
      flows after the ischaemic test (Rel F1) and during the AT (Rel F2) were expressed
      as a percentage of the previous RF values (RF1 and RF2, respectively). During the
      AT, the lag time was calculated (in seconds). As compared to the control
      subjects, RF was significantly lower in the EH group (p < 0.01). During the AT,
      the EH patients showed a statistically lower mean Rel F2 decrease compared to the
      control subjects (p < 0.01). No statistically significant difference occurred in
      the Rel F1 and lag time. These data suggest that the vasoconstrictive capacity of
      the precapillary vessels is impaired in patients with hypertension.

PMID- 9253686
TI  - Skin vasomotor reflexes during inspiratory gasp: standardization by spirometric
      control does not improve reproducibility.
AB  - Arteriovenous anastomoses (AVA) in skin microcirculation are mediated by the
      sympathetic stimuli. The inspiratory gasp test (IG test) triggers the sympathetic
      nervous system, resulting in a decrease in AVA skin blood flow, as measured by
      laser Doppler fluxmetry (LDF). We studied the reproducibility of the IG test
      under carefully standardized respiratory conditions. In each of 19 healthy
      (young) volunteers with a mean skin temperature during the experiment above 28
      degrees C 13 IG tests were performed, either under spirometric control or
      uncontrolled and by using a negative pressure transducer. Starting the IG test
      end-inspiratory results in the most pronounced absolute LDF decrease [140 PU (70
      490)], median (minimum-maximum) as compared to starting end-expiratory [100 PU
      (40-260)] and during inspiration [110 PU (50-350)], respectively, p < 0.001 and p
      < 0.001. Inspiration as fast as possible results in a larger absolute LDF
      decrease [150 PU (40-450)], compared to inspiration in 5 s [120 PU (60-340); p <
      0.02] and in 10 s [130 PU (40-350); p < 0.05]. Continuously sucking negative
      mouth pressure results in a larger LDF decrease [140 PU (30-420)] in comparison
      with taking one deep breath and holding it for 10 s [110 PU (30-270); p < 0.01].
      However, standardization of the IG test did not improve its reproducibility.

PMID- 9253687
TI  - Effects of different intensity endurance training on the capillary network in rat
      skeletal muscle.
AB  - Effects of low- and high-intensity endurance training on the capillary luminal
      diameter and number were studied morphometrically in the rat plantaris muscle.
      Male Wistar-Imamichi rats were divided into three groups: sedentary control group
      (Cont, n = 9), low-intensity (running speed of 20 m/min) training group (T-20, n
      = 8) and high-intensity (running speed of 40 m/min) training group (T-40, n = 7).
      Rats in both training groups were subjected to each treadmill running program for
      60 min/day, 5 days/week for 9 weeks. After 9 weeks of training, citrate synthase
      activity significantly increased in T-40 compared with Cont, but did not change
      in T-20. All morphometric parameters with respect to capillary and muscle fiber
      area were determined in the perfusion-fixed plantaris muscle. The mean muscle
      fiber areas in both T-20 and T-40 were similar to that in Cont. The capillary-to
      fiber ratios were significantly higher in T-20 (2.28 +/- 0.06) and T-40 (2.29 +/-
      0.06) than in Cont (2.00 +/- 0.07). The number of capillaries with a small
      luminal diameter (2-4 microns) was significantly higher in T-20 than in Cont. In
      contrast, T-40 had a significantly higher number of capillaries with a large
      luminal diameter (8-10 microns) compared with Cont. This study indicates that
      endurance training induces changes in the capillary luminal diameter as well as
      capillary number, and that the adaptive response of the capillary luminal
      diameter to endurance training depends on the training intensity.

PMID- 9253688
TI  - Calibration problems for dimensional measurements of microvessel using TV
      methods.

PMID- 9253689
TI  - [Pulsatile diameter change of coronary artery lumen estimated by intravascular
      ultrasound].
AB  - To analyze the pulsatile movement of coronary arterial walls, intravascular
      ultrasound was used to measure the diameter changes in the arterial lumen of 32
      patients with coronary artery disease (CAD group) and five patients with chest
      pain but no CAD (control group). Measurements were performed on segments of the
      proximal left anterior descending coronary artery that were angiographically
      nonstenotic. Following identification of the peak systolic and end-diastolic
      phases using intra-coronary pressure tracings, the luminal diameters were
      measured around the center at 4 degrees intervals using a computer-assisted image
      analyzer. The pulsatile diameter change (dD) and end-diastolic diameter (DD) at
      each interval were analyzed and compared between the CAD and control groups. Mean
      DD did not differ significantly between the CAD group (4.53 +/- 0.69 mm) and the
      control group (4.52 +/- 0.51 mm). In contrast, the mean dD in the CAD group (0.05
      +/- 0.18 mm) was significantly lower than that of the control group (0.13 +/-
      0.12 mm). The mean maximum and minimum standardized percentage pulsatile diameter
      changes were -10.6 +/- 6.2% and 16.2 +/- 5.9%, respectively, in the CAD group,
      and -2.7 +/- 4.6% and 11.7 +/- 1.3%, respectively, in the control group. The mean
      standard deviation of dD was significantly greater in the CAD group (0.182 +/-
      0.05 mm) than in the control group (0.116 +/- 0.04 mm), which indicated dD in CAD
      patients varied to a greater degree than in control patients. The ratio dD/dP (dP
      : pulse pressure) was used as an index of vascular compliance at the site of
      measurement. The mean dD/dP was significantly smaller in the CAD group (1.1 +/-
      2.5 x 10(-3) mm/mmHg) than in the control group (4.0 +/- 3.3 x 10(-3) mm/mmHg).
      Aniso-diametric wall movement in the coronary artery (as indicated by a negative
      dD during systolic expansion) was enhanced in the CAD group compared to the
      control group. This was probably caused by the early stages of the arterial
      sclerotic process as it progressed heterogeneously along the vessel wall. Thus,
      aniso-diametric movement, which is a functional abnormality of the coronary
      arterial wall, appears to antedate detectable morphological changes.

PMID- 9253690
TI  - [Transthoracic digital color Doppler assessment of the left anterior descending
      coronary artery and intramyocardial blood flow].
AB  - Noninvasive assessment of the distal left anterior descending coronary artery and
      intramyocardial blood flow were attempted in 50 consecutive patients (28 males
      and 22 females, mean age [+/-SD] 58 +/- 12 years) using a 7.5 MHz transducer
      (Doppler frequency: 5 MHz) and a SSA-380A ultrasound digital system with special
      optimal settings for the color Doppler examination. Modified apical acoustic
      windows were used to visualize the blood flow in the distal left anterior
      descending coronary artery and the intramyocardial artery. By selecting a sample
      volume (2 mm wide) on the color trace of these blood flows, Doppler spectral
      tracing of the distal left anterior descending coronary artery and
      intramyocardial blood flows could be recorded using pulsed-wave Doppler system.
      Blood flow in the distal left anterior descending coronary artery was detected in
      43 (86%, Vmax = 22 +/- 8.7 cm/sec, Vmean = 16 +/- 5.1 cm/sec) of 50 patients, and
      intramyocardial blood flow in 40 (80%, Vmax = 26 +/- 11.0 cm/sec, Vmean = 19 +/-
      8.5 cm/sec) of 50 patients. Distal left anterior descending coronary artery and
      the intramyocardial blood flows can be imaged by transthoracic digital color
      Doppler echocardiography in the clinical setting.

PMID- 9253691
TI  - [Effect of barnidipine hydrochloride on the autonomic nervous system: difference
      between short- and long-acting components of calcium antagonist].
AB  - Short-acting calcium antagonists have a deleterious effect on the prognosis for
      patients with myocardial ischemia, possibly caused by overactivation of
      sympathetic nerves due to vasodilatation, negative inotropism, or coronary steal.
      However, there is considerable debate about whether long-acting calcium
      antagonists as well as the short-acting calcium antagonists have the same effect.
      Barnidipine-HCl is a newly-developed calcium antagonist with 1:2 short- and long
      acting particles. This study evaluated the changes of autonomic tone due to
      barnidipine. Both the short- and long-acting effect of the calcium antagonist was
      evaluated. Eleven patients with primary hypertension underwent 24-hour ambulatory
      electrocardiogram and blood pressure monitoring before and after the treatment
      with barnidipine. Heart rate and blood pressure were compared before and after
      the medication. Heart rate variability was analyzed with a Marquette 8000/T. High
      frequency power (HF), as a parameter of vagal tone, and the ratio to low
      frequency power (LF), as a parameter of sympathetic tone, were obtained. Twenty
      four-hour average blood pressure decreased significantly during the day, but
      nocturnal hypotension was not observed. Heart rate did not increase. HF decreased
      at the peak of the short- and long-acting components. LF/HF increased at the peak
      of the short-acting component. Short-acting particles of barnidipine had a
      deleterious effect on the autonomic tone, that is overactivation of sympathetic
      tone and suppression of vagal tone. Long-acting particles of barnidipine
      suppressed the vagal tone. These findings suggest that short-acting calcium
      antagonists may cause arrhythmia or deterioration of coronary ischemia.

PMID- 9253692
TI  - [Secretion of atrial natriuretic peptide from the left ventricle and heart in
      patients with hypertrophic cardiomyopathy: relationship with hemodynamic and
      echocardiographic profiles].
AB  - This study investigated whether atrial natriuretic peptide (ANP) secretion from
      the left ventricle occurs and correlated any secretion with the hemodynamic or
      echocardiographic parameters in patients with hypertrophic non-obstructive
      cardiomyopathy (HNCM). Volume overload was induced by intravenous injection of
      low-molecular weight dextran in 19 patients with HNCM and seven normal subjects
      (control group). Simultaneous measurements of plasma ANP concentrations in the
      aortic root, anterior interventricular vein and coronary sinus, and hemodynamic
      parameters were performed before and after volume overload. Echocardiographic
      parameters were measured under the basal conditions in the HNCM group. There was
      no difference in ANP concentrations between the aorta and anterior
      interventricular vein either before or after volume overload in the control
      group, whereas they were significantly higher in the anterior interventricular
      vein than in the aorta both before and after volume overload in the HNCM group,
      suggesting increased ANP secretion from the left ventricle. Moreover, the
      difference in ANP concentrations between these locations was enhanced by volume
      overload. In the HNCM group, the differences in ANP concentrations between these
      locations were positively correlated with the pulmonary capillary wedge pressure
      and left ventricular end-diastolic pressure before and after volume overload, but
      not with left ventricular thickness or left atrial dimension. These results
      suggest that enhanced ANP secretion from the left ventricle in both basal and
      volume overloaded states occurs in HNCM, and this ANP secretion from the left
      ventricle is closely related to left ventricular end-diastolic pressure but not
      to wall thickness and mass index of left ventricle.

PMID- 9253693
TI  - [Effects of oral amezinium metilsulfate in patients with sick sinus syndrome].
AB  - The effects of amezinium metilsulfate (Risumic) were studied in patients with
      sick sinus syndrome. Four males and 11 females with clinical symptoms were
      treated with 0.5 mg/kg for 1 to 40 weeks. In all patients, the length of sinus
      pause observed during 24-hour Holter monitoring was longer than 2.0 sec, and/or
      the sinus node recovery time in the electrophysiologic study was longer than 2.0
      sec. The effects were evaluated by Holter monitoring and standard
      electrocardiography. The total number of heart beats every 24 hours by Holter
      monitoring were significantly increased from 78,917 +/- 15,983 (mean +/- SD) to
      85,753 +/- 17,849 beats after the treatment. The length of the sinus pause was
      significantly decreased from 3.89 +/- 1.24 to 2.36 +/- 1.45 sec. Patients with
      sinus node recovery time of less than 5.0 sec showed the effects especially
      clearly. The total number of premature ventricular contractions was decreased
      from 530 +/- 767 to 123 +/- 182 beats. The PQ, QRS and QTc intervals did not
      change. Only diastolic pressure was slightly increased. Clinical symptoms
      disappeared in almost all patients and the clinical courses were favorable.
      Amezinium metilsulfate, which stimulates the intrinsic sympathetic nervous
      system, increased total heart beat and shortened sinus pause in patients with
      sick sinus syndrome. Few side effects, such as arrhythmogenecity or increase of
      blood pressure were observed. These results show that amezinium metilsulfate is
      useful in the treatment of patients with sick sinus syndrome, if the disease is
      not so severe as to require implantation of a cardiac pacemaker.

PMID- 9253694
TI  - [Pheochromocytoma of the left retroperitoneal paraganglion associated with
      torsade de pointes: a case report].
AB  - A 54-year-old woman developed torsade de pointes with secondary QT prolongation
      due to hypokalemia and hypomagnesemia. Her serum K and Mg levels were 2.5 mEq/l
      and 1.5 mg/dl, respectively. This electrolyte imbalance was due to intentional
      overdosing of metolazone. Attacks of torsade de pointes occurred three times in
      the intensive care unit and were corrected by intravenous lidocaine
      administration. Her serum K level was corrected using KCl infusion, restoring the
      normal QT interval. Routine computed tomography found a left retroperitoneal
      paraganglioma. Urinary and serum catecholamine examination revealed extremely
      high values of epinephrine and norepinephrine. The diagnosis was pheochromocytoma
      in the left retroperitoneal paraganglion. The tumor which was removed measured 70
      x 65 x 60 mm in size. Microscopic examination revealed the characteristic
      patterns of pheochromocytoma.

PMID- 9253695
TI  - [Cardiovascular imaging in a month. A 54-year-old woman complaining of syncopal
      attacks].

PMID- 9253696
TI  - Anomalous origin of a coronary artery as a cause of sudden death.

PMID- 9253697
TI  - Methicillin-resistant Staphylococcus aureus (MRSA)--a re-appraisal of control
      measures in the light of changing circumstances.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains an important
      nosocomial pathogen and the number of affected patients is rising. Increasing
      numbers of patients at risk of acquisition, inadequate isolation facilities,
      problems in identifying the source of outbreaks and the perception amongst some
      clinical colleagues that control measures are too disruptive have contributed to
      the problems faced by infection control teams. Recent controlled studies indicate
      that MRSA is no less virulent than sensitive strains and emphasize the continuing
      need for control measures even where MRSA is endemic. Efforts to control spread
      should be targeted to key clinical areas, such as intensive care units, where the
      impact of infection is likely to be greatest, whilst general infection control
      measures should be strengthened throughout the hospital.

PMID- 9253698
TI  - Microbiological quality of ice in hospital and community.
AB  - A survey was undertaken in response to a report of a clinical infection which had
      been related to an ice-making machine on a hospital ward. A detailed study of the
      ice microflora of 27 ice-making machines was performed. In a subsequent survey,
      ice samples (N = 194) from establishments such as bars and hotels were examined
      for bacterial indicators of hygiene. Samples from hospital ice-making machines
      yielded low numbers of a wide range of potentially opportunistic micro-organisms,
      many of environmental rather than clinical origin. For ice sampled in the
      community, the total aerobic plate count (TAPC) at 37 degrees C for 95% of the
      samples was < 500 cfu/mL, and at 22 degrees C 75% had < 500 cfu/mL. Examination
      for coliforms showed that 69% of samples contained no coliforms, but 20%
      contained > 100 coliforms/100 mL. Escherichia coli was detected in three samples
      but in very low numbers. This report investigates the relevance of ice machines
      to the control of hospital infection, the hygiene of ice in the community,
      discusses the microbiological quality of ice and proposes possible guidelines.

PMID- 9253699
TI  - The potential for catheter microbial contamination from a needleless connector.
AB  - Needleless connectors have been widely introduced into clinical practice to allow
      the connection of syringes and luers to peripheral and central vascular
      catheters. The potential for microbial contamination of catheters via these
      devices is currently unclear. A recently introduced connector, the 'Connecta
      Clave', was assessed by various in-vitro methods. The 'Connecta Clave' is
      specifically devised to separate external components from the fluid pathway. The
      compression seals of 50 devices were contaminated with 1 x 10(4) cfu
      Staphylococcus epidermidis, disinfected with isopropanol, and fluid passed
      through. Only one device allowed organisms to pass through, despite this
      challenge, representing a contamination rate of 2%. In comparison, when 50
      connectors were challenged with 20 cfu of S. epidermidis, no organisms passed
      through the device during use. In the clinical situation, after manipulation, <
      16 cfu of skin organisms were found associated with the compression seal of the
      devices. It is, therefore, likely that the contamination rates in clinical
      practice will be extremely low. Three methods of disinfecting the compression
      seals and associated rims were also evaluated. A combination of alcohol
      chlorhexidine spray, followed by a 70% isopropanol swab, resulted in the most
      efficacious disinfection. The isopropanol swabs produced an adequate disinfection
      rate. The overall results suggest that by use of specially designed connectors,
      not only are needlestick injuries reduced, but the likelihood of microbial
      contamination of catheters via the internal route may also be diminished.

PMID- 9253700
TI  - Outbreak of scarlet fever at a hospital day care centre: analysis of strain
      relatedness with phenotypic and genotypic characteristics.
AB  - An outbreak of scarlet fever involving 12 children occurred at a hospital day
      care centre from February to March 1996. Twenty-five throat isolates of
      Streptococcus pyogenes (GAS, group A streptococcus) available from 24 children,
      including 10 children with scarlet fever and 14 asymptomatic carriers, and one
      asymptomatic staff member were studied for the presence of genes encoding
      streptococcal pyrogenic exotoxin types A (speA), B (speB), and C (speC) and for
      protease activity. Antimicrobial susceptibilities using the E-test, cluster
      analysis by cellular fatty acid composition and random amplified polymorphic DNA
      (RAPD) patterns by means of arbitrarily-primed polymerase chain reaction (APPCR)
      of the isolates were performed to investigate the outbreak. Only one isolate from
      an asymptomatic child possessed the speA gene. All isolates possessed the speB
      gene and 24 (96%) isolates were positive for the speC gene. There was no
      difference in protease activity between isolates from children with scarlet fever
      and from asymptomatic carriers. Thirteen isolates (10 recovered from children
      with scarlet fever, two from asymptomatic children, and one from the staff
      member) were considered to be the same strain according to the identical
      antimicrobial susceptibility profile and RAPD patterns and were also considered
      to be similar by cluster analysis of fatty acid composition. These findings
      suggest that the outbreak was caused by a unique clone of GAS. We conclude that
      RAPD typing and cluster analysis by cellular fatty acids composition both provide
      a powerful tool for epidemiological investigation of GAS infections.

PMID- 9253701
TI  - Low bacterial contamination of nebulizers in home treatment of cystic fibrosis
      patients.
AB  - Many reports have shown bacterial contamination of nebulizers used by patients
      with cystic fibrosis (CF) at home. At the Stockholm CF centre we recommend
      dismantling the equipment, washing, rinsing and drying it after each use, and
      disinfecting it once daily by boiling water or by 2% acetic acid followed by
      drying without rinsing. We studied whether patients comply with these
      recommendations and whether they are sufficient to prevent bacterial
      contamination. Nebulizers from 49 CF patients were investigated, 21 of whom are
      chronically colonized with Pseudomonas aeruginosa and one with Burkholderia
      cepacia. All patients were visited at home. Thirty-nine patients (79%)
      disinfected their equipment after the latest use in accordance with our
      recommendations. Thirty-eight pieces showed no, or only scanty, growth of micro
      organisms belonging to the normal oropharyngeal flora. A moderate growth of alpha
      streptococci was observed from a further five pieces. Four of these had not been
      cleaned after the latest inhalation occasion, and one was visibly dirty.
      Pseudomonads were observed from three pieces; two of these had been disinfected
      by boiling water and one by acetic acid, followed by rinsing in tap water. All
      three had been inadequately dried. Pseudomonads could not be cultured
      simultaneously from the sputum of these three patients. In conclusion, most
      patients comply with our cleaning and disinfection recommendations and these
      recommendations appear satisfactory in preventing bacterial contamination.

PMID- 9253702
TI  - Origin and transmission of methicillin-resistant Staphylococcus aureus in an
      endemic situation: differences between geriatric and intensive-care patients.
AB  - Imported vs. hospital-acquisition of MRSA was assessed in > 6000 patients at a
      large tertiary care teaching hospital. About five percent (5.1%) of patients
      carried MRSA on admission, mostly without clinical symptoms; the highest
      percentage (11.6%) being in geriatric patients. Hospital-acquisition of MRSA
      occurred in 1.7% of patients and was particularly high in intensive-care units
      (5.2%). Phenotype and genotype analysis of 158 MRSA strains isolated from 61
      patients revealed a cluster of closely related strains in the hospital-acquired
      MRSA infections and the close relationship of this cluster to the regional
      epidemic MRSA strain. The MRSA strains imported by geriatric patients were
      genetically different, did not spread between geriatric patients and were only a
      minor source of nosocomial infection.

PMID- 9253703
TI  - Fungaemia due to Fusarium spp. in cancer patients.
AB  - Five cases of fungaemia due to Fusarium spp. in cancer patients are described.
      Two were breakthrough cases, despite ongoing therapy with amphotericin B. Three
      were caused by Fusarium solani, one by F. oxysporum and one by F. dimerum. Four
      patients died, three of them despite therapy with amphotericin B for between 5-37
      days. We describe only the second reported case of F. dimerum fungaemia. Since
      1972, 93 cases of systemic infection with Fusarium spp. have been described: 43
      had positive blood cultures and the overall mortality was 72%.

PMID- 9253704
TI  - Incidence surveillance of wound infection in hernia surgery during
      hospitalization and after discharge in a university hospital.
AB  - A six-month prospective incidence surveillance of wound infection was conducted
      in the department of general surgery of the Rio de Janeiro University Hospital.
      Postoperative infections were classified according to Centers for Disease Control
      criteria. This study reports a rate of 14.04% in surgical infections limited to
      herniorrhaphy and detected by surveillance. The majority (87.50%) of them were
      only apparent after hospital discharge. Fourteen out of 16 patients (88.60%) were
      not deemed to be at risk for surgical infections. Staphylococcus aureus was the
      most important pathogen associated with infection. This report shows that
      community surveillance is necessary to determine accurate rates of hospital
      acquired infection and will help establish prevention and control policies in
      Brazil.

PMID- 9253705
TI  - Fatal primary cutaneous aspergillosis in a bone marrow transplant recipient:
      nosocomial acquisition in a laminar-air flow room.
AB  - A case of primary cutaneous aspergillosis occurring in an allogeneic bone marrow
      transplant recipient in a laminar airflow room is reported. The patient developed
      grade III graft-versus-host-disease and epidermolysis. Although the patient had
      remained in his laminar airflow room from the graft onward, he subsequently
      developed primary cutaneous aspergillosis. The aspergillosis became invasive and
      the patient died. The patient was probably contaminated by air containing conidia
      when he left the sterile room for endoscopy, and the fluidized bed used may have
      contributed to the local development of the disease. This nosocomial
      aspergillosis stresses the necessity of performing invasive procedures under
      laminar airflow protection to prevent Aspergillus contamination in
      immunocompromised hosts at risk for aspergillosis.

PMID- 9253706
TI  - Risk of nosocomial infection during a 50-day surgeon strike.

PMID- 9253707
TI  - Acetic acid treatment of pseudomonal postoperative wound infection.

PMID- 9253708
TI  - Acetaminophen, N-acetyl-benzo-quinoneimine, and apoptosis.

PMID- 9253709
TI  - The breast cancer gene product TSG101: a regulator of ubiquitination?
AB  - Sequence analysis is a powerful tool to obtain structural and functional
      information about genes and their products. Here we show that TSG101, a gene
      subjected to somatic mutations in breast cancer, contains an amino terminal
      domain that is a homologue of ubiquitin conjugating enzymes (UBCs) and not, as
      previously proposed, DNA-binding domains. As the UBC active site residue is
      replaced in the TSG101 sequence in a similar manner to several other members of
      the UBC family, we propose a role for TSG101 in regulating the ubiquitination of
      short-lived gene products.

PMID- 9253710
TI  - Molecular understanding of hematopoietin/cytokine receptor signaling defects in
      hematopoietic disorders.
AB  - Hematopoietic growth factors (HGFs) act on the hematopoietic cells via binding to
      specific cell surface receptors. Many HGF receptors have certain common
      structural features and have therefore been grouped in the superfamily of
      hematopoietin or cytokine receptors, also referred to as the class I receptor
      superfamily [1, 2]. Activation of these receptors by their cognate growth factors
      is mediated through the formation of dimeric or oligomeric complexes of receptor
      structures. Some HGF receptors are composed of heteromeric complexes, comprising
      two or three different receptor chains. For instance, this is the case for
      receptors of interleukins 2, 3, and 5 and granulocyte-macrophage colony
      stimulating factor [3]. Other receptor structures, for example, those of
      granulocyte colony-stimulating factor and erythropoietin, form homodimeric
      complexes upon growth factor binding [2, 4]. This brief overview begins with an
      introduction of the major principles of HGF receptor signaling: this is followed
      by a discussion of the consequences of HGF receptor signaling defects for the
      development of disorders of the hematopoietic system and the presentation of
      clinical examples of such diseases.

PMID- 9253711
TI  - Gene-based strategies for the immunotherapy of cancer.
AB  - T lymphocytes play a crucial role in the host's immune response to cancer.
      Although there is ample evidence for the presence of tumor-associated antigens on
      a variety of tumors, they are seemingly unable to elicit an adequate antitumor
      immune response. Modern cancer immunotherapies are therefore designed to induce
      or enhance T cell reactivity against tumor antigens. Vaccines consisting of tumor
      cells transduced with cytokine genes in order to enhance their immunogenicity
      have been intensely investigated in the past decade and are currently being
      tested in clinical trials. With the development of novel gene transfer
      technologies it has now become possible to transfer cytokine genes directly into
      tumors in vivo. The identification of genes encoding tumor-associated antigens
      and their peptide products which are recognized by cytotoxic T lymphocytes in the
      context of major histocompatibility complex class I molecules has allowed
      development of DNA-based vaccines against defined tumor antigens. Recombinant
      viral vectors expressing model tumor antigens have shown promising results in
      experimental models. This has led to clinical trials with replication-defective
      adenoviruses encoding melanoma-associated antigens for the treatment of patients
      with melanoma. An attractive alternative concept is the use of plasmid DNA, which
      can elicit both humoral and cellular immune responses following injection into
      muscle or skin. New insights into the molecular biology of antigen processing and
      presentation have revealed the importance of dendritic cells for the induction of
      primary antigen-specific T cell responses. Considerable clinical interest has
      arisen to employ dendritic cells as a vehicle to induce tumor antigen-specific
      immunity. Advances in culture techniques have allowed the generation of large
      numbers of immunostimulatory dendritic cells in vitro from precursor populations
      derived from blood or bone marrow. Experimental immunotherapies which now
      transfer genes encoding tumor-associated antigens or cytokines directly into
      professional antigen-presenting cells such as dendritic cells are under
      evaluation in pre-clinical studies at many centers. Gene therapy strategies, such
      as in vivo cytokine gene transfer directly into tumors as well as the
      introduction of genes encoding tumor-associated antigens into antigen-presenting
      cells hold considerable promise for the treatment of patients with cancer.

PMID- 9253712
TI  - Cardiotrophin-1 and the role of gp130-dependent signaling pathways in cardiac
      growth and development.
AB  - The reactivation of an embryonic pattern of gene expression is a central feature
      common to virtually all forms of cardiac hypertrophy. Unraveling the regulatory
      mechanisms, growth factors and cytokines controlling gene expression and cell
      fate during cardiac development may therefore have implications for our
      understanding of cardiac hypertrophy in the adult. Along this line, a cDNA
      expression library was established from an embryonic stem cell-based in vitro
      model of cardiogenesis, and screened for clones that would induce an increase in
      cell size in cultured cardiomyocytes. This experimental strategy resulted in the
      isolation of a novel cytokine, cardiotrophin-1 (CT-1), that activates several
      features of cardiomyocyte hypertrophy in vitro, including sarcomeric organization
      and embryonic gene expression. CT-1 displays structural similarities to the
      interleukin (IL)-6 related cytokines. Furthermore, receptor binding studies and
      functional studies reveal that CT-1 shares the signal transducing receptor
      components gp130 and LIFR with the previously identified members of the IL-6
      cytokine family. CT-1 rapidly activates gp130 and LIFR tyrosine phosphorylation
      in cultured cardiac myocytes. The growth promoting effects of CT-1 therefore
      indicate that signaling pathways emanating from gp130 and LIFR are coupled to
      cardiomyocyte hypertrophy. In support of this notion, the simultaneous
      overexpression of IL-6 and the IL-6 receptor in transgenic mice has been shown to
      result in a constitutive tyrosine phosphorylation of gp130 in the myocardium and
      cardiac hypertrophy. The striking phenotype of gp130 null-mutant mice, generated
      by homologous recombination, implies gp130 in cardiac development as well: mutant
      mice exhibit severe ventricular hypoplasia, suggesting a role for gp130-dependent
      signaling pathways in the expansion of the compact layer of the ventricular
      myocardium. CT-1 is expressed at high levels in the myocardium during the course
      of cardiogenesis, and promotes the proliferation and survival of embryonic
      cardiomyocytes. CT-1 may therefore represent a candidate cytokine to activate
      gp130 during cardiac development. In summary, cytokines signaling through gp130
      are emerging as potent regulators of embryonic heart development and adult
      cardiac hypertrophy.

PMID- 9253713
TI  - Genetic control of interleukin 12 responsiveness: implications for disease
      pathogenesis.
AB  - We examined the effect of genetic background on Th1/Th2 development. We discuss
      data demonstrating that genetic background is an important determinant of
      interleukin-12 (IL-12) responsiveness and the potential implications for disease
      progression in murine experimental leishmaniasis. Genetic analysis of the
      differential control of IL-12 responsiveness led to the identification of a
      controlling locus on the middle portion of murine chromosome 11. This genetic
      region (or its human counterpart, 5q31) has been associated with increased
      disease susceptibilities for several atopic, infectious, and autoimmune
      disorders. We discuss potential roles for genetic control of IL-12 responsiveness
      in the development of these diseases.

PMID- 9253714
TI  - Evidence of alternative promoters directing isoform-specific expression of human
      endothelin-converting enzyme-1 mRNA in cultured endothelial cells.
AB  - The endothelins, a family of closely related vasoactive and mitogenic peptides,
      are thought to play an important role in cardiovascular pathophysiology. The
      conversion of the inactive precursor "big endothelin" to the biologically active
      peptide is catalyzed in vitro and in vivo by endothelin-converting enzymes (ECE).
      Recently the cDNA cloning of two homologous proteins, termed ECE-1 and ECE-2, has
      been reported. ECE-1 may play a key role in the activation and regulation of the
      cardiovascular endothelin proteolytic cascade. ECE-1 mRNA is expressed in two
      isoforms, termed alpha and beta, which are identical except for the 5'-terminal
      regions. To investigate the transcriptional regulation of isoform-specific ECE-1
      mRNA expression we isolated phage clones from a human genomic library and
      identified the alpha- and beta-specific exons of ECE-1. The exon/intron
      organization of the 5'-terminal region of the human ECE-1 gene in conjunction
      with putative transcription initiation start sites suggests the existence of two
      alternative promoters, each directing the expression of either isoform. A reverse
      transcription/polymerase chain reaction assay indicated differential mRNA
      expression of ECE-1 isoforms. Using a luciferase reporter gene assay, we found
      that the genomic region upstream of exon 1 alpha confers strong promoter activity
      in the human endothelial cell line ECV 304, which was previously shown to express
      predominantly ECE-1 alpha mRNA. Transfection of serial deletion mutants in ECV304
      cells indicated the existence of three positive and also one negative regulating
      element within 2 kb of the alpha-promoter region. Luciferase reporter gene
      studies also revealed that the genomic region upstream of exon 3, which encodes
      the putative ECE-1 beta specific N-terminus, was able to direct luciferase
      expression in primary cultured bovine aortic endothelial cells, indicating the
      existence of an alternative promoter. Transfection of nested deletions spanning
      1.2 kb upstream of the putative translation initiation codon of ECE-1 beta
      suggested the existence of three positive regulating regions within the beta
      specific promoter. Both ECE-1 promoters lack TATA or CAAT boxes, and the two show
      different patterns of consensus sequences for transcription factors, suggesting a
      differential transcriptional regulation of isoform-specific ECE-1 mRNA
      expression.

PMID- 9253716
TI  - Comparative research on leukemia and related diseases: an introduction to a
      scientific approach.
AB  - Publication in this journal of the abstracts of the Nineteenth Symposium of the
      International Association for Comparative Research on Leukemia and Related
      Diseases in Mannheim/Heidelberg led editor and publisher to suggest an article
      introducing comparative research in leukemia and related diseases. Our survey
      briefly summarizes the history of this symposium, as it evolved from a meeting on
      animal leukemia virus into one dealing with viral and genetic aspects of human
      and animal leukemia and related diseases. The scientific evolution of the Abelson
      murine leukemia virus with its abl oncogene in the 1970s to what currently
      appears as the most reliable marker for human chronic myeloid leukemia is merely
      one example.

PMID- 9253715
TI  - Acetaminophen metabolism and cytotoxicity in PC12 cells transfected with
      cytochrome P4502E1.
AB  - Although a number of studies confirm the important role of metabolites in the
      cytotoxicity of acetaminophen, its precise mechanisms remain unknown.
      Acetaminophen is metabolized by microsomal enzymes. Cytochrome P4502E1 (CYP2E1)
      mediated N-hydroxylation results in the formation of N-acetyl-benzo-quinoneimine,
      a highly reactive intermediate. We examined biochemical parameters related to
      necrotic and apoptotic processes in acetaminophen-exposed PC12 cells is and in a
      PC12 cell line genetically engineered to express human CYP2E1. Both the
      [3H]thymidine incorporation test and the protein assay uniformly showed dose- and
      time-related significant growth retardation in both cell lines exposed to the
      drug. This was more evident in CYP2E1-transfected cells. Moreover, the cytotoxic
      effect of acetaminophen was increased as evidenced by lactate dehydrogenase
      activity in the culture medium. Both random oligonucleotide primed synthesis
      assay and enzyme-linked immunosorbent assay revealed significant DNA
      fragmentation in both cell lines, which was greater in transfected cells,
      reaching about 11% of total cellular DNA. These results were confirmed by flow
      cytometry and microscopic examination of cell nuclei. Intracellular calcium
      levels were increased only in transfected cells, approximately threefold when 5
      mM acetaminophen was administered for 48 h. These results indicate the cytotoxic
      effects of acetaminophen via apoptosis, necrosis, and growth retardation. While
      the precise mechanism remains obscure, it seems that DNA fragmentation and
      apoptotic cascade represent a preliminary biochemical event in acute cell death,
      and that acetaminophen bio-transformation by CYP2E1 stimulates this pathway.

PMID- 9253717
TI  - Use of a breathable glove liner for prevention of delayed hypersensitivity to
      rubber accelerators.

PMID- 9253718
TI  - Cost-effectiveness of the varicella vaccine for administration to health care
      workers.

PMID- 9253719
TI  - Can heavy lifting cause epididymitis?

PMID- 9253720
TI  - The competitive advantage of a healthy work force: opportunities for occupational
      medicine.

PMID- 9253721
TI  - ACOEM Code of Ethical Conduct. American College of Occupational and Environmental
      Medicine.

PMID- 9253722
TI  - A proposed revision of the ACOEM Code of Ethics. American College of Occupational
      and Environmental Medicine.
AB  - The 1993 revision of the American College of Occupational and Environmental
      Medicine (ACOEM) Code of Ethical Conduct is insufficiently demanding of
      physicians in important areas, such as conflicts of interest, reporting unethical
      or incompetent colleagues, and confidentiality of medical information. The
      International Commission on Occupational Health's International Code of Ethics,
      drafted for all occupational health professionals worldwide, does not apply well
      to American legal and economic relationships. The best way to revise the 1993
      ACOEM Code is to incorporate key provisions of the American Occupational Medical
      Association's 1976 Code. A proposed revised ACOEM Code is presented combining
      elements of the 1993 ACOEM and 1976 AOMA Codes. The resulting code is a clearer
      description of individual standards of conduct and group ideals.

PMID- 9253723
TI  - Effect of chronic low-level exposure to jet fuel on postural balance of US Air
      Force personnel.
AB  - This study used the postural stability technique to investigate the neurological
      effects of cumulative low-level exposure to raw JP-8 jet fuel vapor on aircraft
      maintenance personnel. All subjects performed two sets of four 30-second postural
      sway tests. The results of mean cumulative exposure levels (in parts per million
      +/- standard error of mean) were the following: naphthas, 1308 +/- 292; benzene,
      21.2 +/- 5.7; toluene, 23.8 +/- 6.1; and m-,o-, p-xylene, 22.7 +/- 5.4. Covariate
      adjusted regression analysis of the exposed group data showed a statistically
      significant association (P < 0.05) between the solvents (benzene, toluene, and
      xylene) and increased postural sway response. For all solvent exposures, the
      "eyes closed, on foam" test provided the strongest association between sway
      length and JP-8 benzene (r2 range, 0.45 to 0.52), implying subtle influence on
      vestibular/proprioception functionalities.

PMID- 9253724
TI  - Cancer risk and mortality patterns among silicotic men in Sweden and Denmark.
AB  - Data from nationwide registry-based cohorts of patients hospitalized for
      silicosis in Sweden from 1965 to 1983 and Denmark from 1977 to 1989 were linked
      to national cancer registries in both countries and to mortality data in Sweden
      to evaluate the risk of cancer and other disorders among hospitalized silicotic
      patients. The overall cancer standardized incidence ratio (SIR) was 1.5 (95%
      confidence interval [CI], 1.3 to 1.7) in Sweden and 1.7 (95% CI, 1.2 to 2.3) in
      Denmark, primarily because of elevations in primary lung cancer in both Sweden
      (SIR, 3.1; CI, 2.1 to 4.2) and Denmark (SIR, 2.9; CI, 1.5 to 5.2). For Sweden,
      the all-causes standardized mortality ratio (SMR) was 2.0 (1.9 to 2.2). The SMR
      for all malignancies was 1.5 (1.2 to 1.7), primarily because of excesses of lung
      cancer (SMR, 2.9; CI, 2.1 to 3.9). The significant increase in mortality for all
      infectious and parasitic conditions (SMR, 11.2) was primarily due to tuberculosis
      (SMR, 21.8). Significant excesses in mortality from silicosis (SMR, 523),
      bronchitis (SMR, 2.6) and emphysema (SMR, 6.7) contributed to the elevation in
      nonmalignant respiratory deaths (SMR, 8.8), whereas excess mortality from
      musculoskeletal disorders (SMR, 5.9) was due to six deaths from autoimmune
      diseases. Despite limitations of the available data, our findings are consistent
      with previous reports indicating that silicotic patients are at elevated risk of
      lung cancer, nonmalignant respiratory diseases, tuberculosis, and certain
      autoimmune disorders.

PMID- 9253725
TI  - An updated meta-analysis of formaldehyde exposure and upper respiratory tract
      cancers.
AB  - In this study, we summarize 47 epidemiologic studies related to formaldehyde
      exposure and use meta-analytic techniques to assess findings for cancers of the
      lung, nose/nasal sinuses, and nasopharynx. Our analyses indicate that workers
      with formaldehyde exposure have essentially null findings for lung cancer and a
      slight deficit of sinonasal cancer. Nasopharyngeal cancer rates were elevated
      moderately in a minority of studies. Most studies, however, did not find any
      nasopharyngeal cancers, and many failed to report their findings. After
      correcting for underreporting, we found a meta relative risk of 1.0 for cohort
      studies. Case-control studies had a meta relative risk of 1.3. Our review of the
      exposure literature indicated that the nasopharyngeal cancer case-control studies
      represented much lower and less certain exposures than the cohort studies. We
      conclude that the available studies do not support a causal relation between
      formaldehyde exposure and nasopharyngeal cancer. This conclusion conflicts with
      conclusions from two previous meta-analyses, primarily because of our
      consideration of unreported data.

PMID- 9253726
TI  - Cost benefit of sumatriptan to an employer.
AB  - Benefit and occupational health managers need information on whether new
      treatments, such as sumatriptan, for migraine headache improve organizational or
      individual performance. A work productivity outcomes assessment was conducted
      among sumatriptan-using employees of an Independent Practice Association-health
      maintenance organization population. Of the 164 sumatriptan users, 101 full-time
      employees were surveyed by telephone once in an open-label, before-after design.
      The results revealed that lost labor costs, a function of days missed from work
      and reduced productivity at work as a result of migraine, were decreased after
      sumatriptan treatment initiation. Incremental benefit of this reduction in lost
      productivity is valued at $435/month per employee. The sumatriptan cost
      associated with this benefit is $43.78/month. The benefit-to-cost ratio is 10:1.
      Other costs and benefits were excluded. In conclusion, the availability of
      sumatriptan for migraine headache treatments in this IPA-HMO resulted in improved
      work productivity and had a net benefit for the employer.

PMID- 9253727
TI  - Occupational lead exposure and hearing loss.
AB  - Studies of adults, children, and laboratory animals suggest an association
      between lead exposure and hearing loss. A causal relationship might direct
      mandated medical surveillance of lead-exposed workers to include audiometric
      testing. A cross-sectional, computerized dataset was obtained from a private
      occupational health screening company to examine the relationship between blood
      lead level and hearing loss. Audiometry and blood lead results were available for
      183 workers. A statistically significant correlation was found between blood lead
      level and an elevated hearing threshold at 400 Hz (P = 0.03); no other
      frequencies showed such a correlation. This finding suggests either an
      interaction between nose exposure and lead, interaction of other exposure factors
      (such as cigarette smoking), or that factors other than biomechanical ones render
      the organ of Corti more susceptible at 4000 Hz. Further evaluation of these
      questions should be undertaken. Computerized databases created for worker
      surveillance may be a source for data useful for examining other causal
      connections in occupational settings.

PMID- 9253728
TI  - An evaluation of peer and professional trainers in a union-based occupational
      health and safety training program.
AB  - Social cognitive theory posits that behavior can be changed by observing others
      perform or describe performance of behaviors. This framework was applied to
      understanding health behavior change associated with workplace health and safety
      training. Questionnaires were developed and administered to 426 workers at a
      United Automobile Worker's Union health and safety training program. Participants
      received training from one of three trainers: (1) local union discussion leaders
      (LUDLs), (2) professional staff trainers, or (3) LUDLs with professional staff
      trainers. Data were collected in three phases: before, after, and three months
      post-training. Findings show that subjects trained by LUDLs identify most closely
      with their instructors, whereas subjects trained by staff trainers identify least
      closely with them. In addition, workers trained by LUDLs reported changing
      behavior as a result of training more often than workers trained by others.

PMID- 9253729
TI  - Occupational injuries among urban recyclers.
AB  - In this article, we describe the emergence of urban recycling as a new trade and
      discuss the new pattern of injuries among its practitioners. We conducted a
      retrospective chart review and convenience survey at an urban homeless health
      center. We found a high prevalence of severe, costly injuries, many of which are
      amenable to prevention. Lacerations, infections, needle sticks, and blunt trauma
      are all common in this group. Some cases are extremely expensive or even lethal.
      We conclude that a new trade and a new pattern of injuries associated with it
      have emerged around recycling.

PMID- 9253730
TI  - Reversing blindness--one child at a time.

PMID- 9253731
TI  - Congenital aphakia.

PMID- 9253732
TI  - Treating amblyopia.

PMID- 9253733
TI  - Mechanized anterior capsulectomy.

PMID- 9253734
TI  - Childhood aphakic glaucoma.

PMID- 9253735
TI  - Random dot stereoacuity of preschool children. ALSPAC "Children in Focus" Study
      Team.
AB  - PURPOSE: Commercially available book-format random dot stereopsis tests for
      children are quick and simple to use, but provide accurate measurement of
      stereoacuity only in children age 5 years or older. Alternative methods for
      preschool children provide only pass/fail information or require lengthy
      laboratory-based protocols. To address the need for a quick and accurate measure
      of random dot stereoacuity in the preschool age range, we developed a new book
      format random dot stereoacuity test. METHODS AND RESULTS: A total of 25 potential
      shapes for the new test were evaluated in a group of 43 healthy full-term
      children aged 3 years +/- 2 months. Eleven shapes that were identified
      successfully by more than 95% of the 3-year-olds were selected to be incorporated
      into the preschool stereotest. The preschool random dot stereotest books were
      administered to more than 1000 normal children and pediatric patients in multiple
      settings: a research laboratory (Retina Foundation SW), a population screening
      project (University of Bristol, UK), eye clinics (Children's Medical Center,
      Dallas, Tex), and a day care center (Federal University, Sao Paulo, Brazil).
      Randot, Lang 1, Frisby, or Titmus stereoacuity tests also were administered.
      Orthoptic or ophthalmic examinations were obtained for all children as a gold
      standard. Outcome measures were success rate and concordance with the clinical
      examination. Sensitivity, specificity, and accuracy exceeded 0.90 both in
      clinical and screening settings. CONCLUSIONS: The preschool random dot books had
      a higher success rate than other tests in the preschool age range and provided
      accurate measurement of stereoacuity in the 3- to 5-year-old age range.

PMID- 9253736
TI  - Visual outcome of craniopharyngioma in children.
AB  - PURPOSE: To assess the visual outcome of children with craniopharyngioma and
      identify predictors of visual loss. METHODS: A retrospective analysis of all
      patients younger than 18 at presentation who were evaluated between 1984 and 1995
      was performed. Visual outcome was assessed as a function of age, systemic
      symptoms, visual acuity at presentation, and need for postoperative radiotherapy.
      RESULTS: Thirty-one patients were identified, with a mean age of 7.7 years
      (range, 1.2 to 16.8 years) at the time of surgical resection. The initial visual
      acuity (known in 20 patients at presentation) in the better-seeing eye was > or =
      20/40 in 14 (70%) patients and < 20/200 in 2 (10%) patients. Twelve (39%)
      patients presented with visual symptoms and 15 (48%) with systemic symptoms. All
      patients underwent surgical resection; some patients required multiple surgeries
      (52%) or adjuvant radiotherapy (48%). The mean postsurgical follow up was 6.5
      years (range, 4 days to 25 years). Postoperative visual acuity was > or = 20/40
      in the better eye in 22 (71%) patients; 8 (26%) patients had visual acuity <
      20/200 in their better-seeing eye. Optic atrophy developed in 51 eyes of 27
      patients (81%). CONCLUSIONS: Craniopharyngioma presents with visual symptoms in
      children and is associated with significant permanent visual dysfunction. Age
      younger than 6 years at presentation and visual symptoms at presentation were
      associated with a significantly poorer visual outcome. Craniopharyngioma should
      be considered in the differential diagnosis of every child with amblyopia,
      particularly when no amblyogenic factors such as anisometropia or strabismus are
      present.

PMID- 9253737
TI  - Diplopia following subcutaneous injections of botulinum A toxin for facial
      spasms.
AB  - PURPOSE: To study the incidence, cause, recovery time, and prevention of diplopia
      following subcutaneous injection of botulinum A toxin for the treatment of facial
      spasms. METHODS: Patients who experienced diplopia after botulinum A toxin
      injections had their deviations examined in detail. When the muscle that caused
      diplopia was identifiable, the injection closest to that muscle was omitted in
      the next treatment in an attempt to prevent diplopia. RESULTS: Of 250 patients
      receiving about 1500 sets of injections, 25 (1.7%) incidents of diplopia occurred
      in 10 patients. Excluding two patients who declined further treatment after
      having diplopia on their first botulinum A toxin treatment, seven of the
      remaining eight patients had multiple incidents of diplopia. The most common
      pattern of diplopia was "uncertain diagnosis." The most common identifiable cause
      of diplopia was paresis of the inferior oblique muscle. Omission of the injection
      into the central portion of the lower eyelids in the next treatment prevented
      recurrence of diplopia in only one of the four patients. No significant
      correlation between botulinum A toxin doses injected and times to recovery was
      noted. CONCLUSIONS: Diplopia following botulinum A toxin treatment is uncommon.
      Seven patients (3% of patients studied) had 22 episodes of diplopia (88% of
      episodes). When diplopia occurs, it tends to recur on reinjection, sometimes with
      a prolonged recovery time. This response may not be dose dependent. The
      extraocular muscles of some patients may be more susceptible to chemodenervation
      than others, or botulinum A toxin may diffuse to extraocular muscles more easily
      in some patients than in others.

PMID- 9253738
TI  - Transscleral diode laser cyclophotocoagulation for refractory pediatric
      glaucomas.
AB  - PURPOSE: To evaluate the success of contact transscleral cyclophotocoagulation
      (TDC) in patients with refractory pediatric glaucomas. METHODS: Twenty-six eyes
      of 20 patients with therapy-resistant pediatric glaucomas were included in this
      retrospective study. Subgroup analysis was performed for patients 10 or younger
      and patients older than 10 at time of first TDC procedure. Diode laser
      cyclophotocoagulation was applied using a fiber optic G-probe. Follow up until
      time of failure or for a minimum of 6 months was obtained for all procedures in
      all eyes. Failure was defined as intraocular pressure (IOP) greater than 21 mm
      Hg, repeat of TDC due to clinically inadequate IOP control, progression to
      another procedure, or serious complication. RESULTS: Baseline mean pretreatment
      IOP was 34.2 +/- 10.4 mm Hg (range, 15 to 62 mm Hg). Ten of 26 eyes (38%) were
      successful 6 months after initial TDC. A mean decrease in IOP of 10.3 +/- 14.7 mm
      Hg was noted after the first procedure (P < 0.05). Eighteen eyes (70%) were
      retreated at least once. The mean decrease in IOP for all patients after all
      procedures was 12.9 +/- 13.4 mm Hg (P < 0.001). This represents a mean percent
      decrease in IOP of 33.2 +/- 6.9%. The overall success rate was 50%, including
      retreated patients. The younger and older subgroups did not differ with regard to
      overall success, time to failure, or retreatment rats. One patient suffered a
      retinal detachment. Visual loss was noted in 4 of 22 eyes with reliable visual
      acuity measurements. CONCLUSION: TDC is an effective means of decreasing IOP in
      some patients with refractory pediatric glaucomas. Although the retreatment rate
      is high, the procedure generally is well tolerated with few complications.

PMID- 9253740
TI  - Effects of strabismus surgery on corneal topography.
AB  - BACKGROUND: Changes in refraction follow surgery on the extraocular muscles. We
      examined corneal topography before and after medial or lateral rectus muscle
      recession using a computer-assisted topographic analysis system. METHODS: A total
      of 36 patients (52 eyes) were examined. Measurements were taken 1 day before
      surgery and 1, 15, and 30 days after surgery. RESULTS: A significant change in
      astigmatic power was detected 1 day after surgery in the meridian of the recessed
      muscle, evidencing a localized flattening of the cornea. Induced astigmatism
      decreased over time. At 30 days following surgery, 6% of patients evidenced a
      residual change higher than 1 diopter (D); 12% evidenced a residual change higher
      than 0.5 D. CONCLUSION: The increase of astigmatic power recorded 1 day after
      surgery is higher for medial rectus muscle recession than for lateral rectus
      muscle recession. Corneal topography changes, located mainly in the meridian of
      the recessed muscle and the optical zone, are greatly reduced or gone within 1
      month of surgery.

PMID- 9253739
TI  - Predictive value of regression and theoretical IOL formulas in pediatric
      intraocular lens implantation.
AB  - PURPOSE: Intraocular lenses (IOLs) are being implanted in children with greater
      frequency and in a wider age range. The accuracy of available regression and
      theoretical formulas in predicting correct IOL power for pediatric eyes, however,
      has not been reported. METHODS: We reviewed medical records of 47 consecutive
      pediatric IOL implantations after cataract extraction that met inclusion
      criteria. Age at surgery ranged from 2 months to 10 years, with measured axial
      lengths of the eye between 18.6 and 26.7 mm. For the purpose of this study, the 2
      month postoperative refraction was considered the post-IOL refractive outcome.
      Using preoperative globe axial length, corneal curvature, IOL power, and the A
      constant for the lens provided by the manufacturer, we employed the four common
      IOL power formulas (one regression formula [SRK-II] and three theoretical
      formulas [SRK-T, Holladay, and Hoffer Q]) to predict refractive outcome. RESULTS:
      The average difference between predicted and actual postoperative refractive
      error ranged from 1.2 to 1.4 diopters (D) for all formulas. Predicted
      postoperative refraction was less than the actual in 89 calculations and greater
      in 99. No significant differences in predictive accuracy were found in any of the
      axial length groups (group 1 P = 0.79, group 2 P = 0.42, and group 3 P = 0.86).
      All formulas were slightly less accurate in group 3 patients (shortest eyes). In
      this group, the Hoffer Q formula had the lowest error (1.4 D) and the SRK-II had
      the highest error (1.8 D). The difference was not statistically significant (P =
      .86). CONCLUSIONS: In our pediatric study eyes, all four IOL power calculation
      formulas predicted mean refractive outcome within 1.4 D. Theoretical formulas did
      not outperform the regression formula.

PMID- 9253741
TI  - Bilateral central retinal artery occlusion in a neonate.

PMID- 9253742
TI  - Prolonged oculocardiac reflex during strabismus surgery under topical anesthesia.

PMID- 9253743
TI  - Leber's congenital amaurosis in 22 affected members of one family.

PMID- 9253744
TI  - Endoscopic goniotomy for congenital glaucoma.

PMID- 9253745
TI  - Inadvertent Faden procedure.

PMID- 9253746
TI  - Amblyopia resulting from shield ulcers and plaques of the cornea in vernal
      keratoconjunctivitis.

PMID- 9253747
TI  - Determination of vascular compliance, interstitial compliance, and capillary
      filtration coefficient in rat isolated perfused lungs.
AB  - Gravimetric methods are useful for investigating mechanisms of edema formation.
      In isolated lungs perfused under isogravimetric conditions, important information
      may be gained by analyzing the weight changes induced by a sudden change in
      capillary pressure. In the present study, we investigated the possibility to
      analyze this weight change by a biexponential equation and use the coefficients
      obtained to derive vascular compliance (Cv), interstitial compliance (Ci) and the
      capillary filtration coefficient (Kf,c). Fitting the data of the weight gain to a
      biexponential curve explained the data significantly better than fitting it to a
      monoexponential curve, suggesting that two phases can be separated. The first
      phase is thought to represent vascular filling and was completed for 95% after
      0.57 +/- 0.21 min (n = 30). In contrast, 95% completion of phase 2, which relates
      to interstitial filling, took 18.4 +/- 13.9 min (n = 30). The values obtained for
      Cv, Ci and Kf,c were 0.064 +/- 0.018 ml/cm H2O, 0.067 +/- 0.030 ml/cm H2O, and
      0.588 +/- 0.206 ml/min/cm H2O/100 g lung wet weight, respectively. Treatment of
      the lungs with platelet activating factor caused no changes in Cv or Ci, but
      increased Kf,c suggesting increased endothelial permeability. We conclude that
      analysis of weight changes by a biexponential equation offers a quick and
      reliable way to analyze factors related to edema formation.

PMID- 9253748
TI  - A rapid electron-capture gas chromatographic method for the quantification of
      fluvoxamine in brain tissue.

PMID- 9253749
TI  - Dipalmitoylphosphatidylcholine/linoleic acid mixed unilamellar vesicles as model
      membranes for studies on novel free-radical scavengers.
AB  - Large unilamellar vesicles (LUVs) are generally accepted to be a suitable model
      for peroxidation studies. In the present report, dipalmitoylphosphatidylcholine
      (DPPC)/linoleic acid-mixed LUVs were employed as model membranes to verify the
      inhibitory effect of tocopherol (an efficient representative antioxidant) against
      2,2'-azobis(2-amidinopropane)hydrochloride-induced peroxidation (evaluated by
      monitoring conjugated diene accumulation). In this model, the appropriate
      experimental conditions (particularly, liposome composition and peroxidation
      temperature) were selected following characterization of bilayer physical state,
      and not only by evaluation of peroxidation rate. Thus, the experiments described
      provide a routine screening procedure that would be appropriate for assessing the
      activity profile of novel free-radical scavengers.

PMID- 9253750
TI  - A simple method for measuring dopamine release from rat brain slices.
AB  - In many circumstances, rapid information is required about the effects of drugs
      on neurotransmitter release in brain, and a common method used is measurement of
      radiolabelled release from superfused brain slices or synaptosomes in vitro.
      However, the method requires expensive equipment and is not readily adapted to
      the measurement of endogenous release. The method described here uses readily
      available cheap chromatographic columns to measure both radiolabelled and
      endogenous dopamine (DA) release from striatal slices in repeated incubation
      samples. The results showed that the [3H]DA release is sensitive to temperature,
      K(+)-stimulation, and to both a DA agonist (pergolide) and an antagonist
      (eticlopride). Endogenous DA release was also stimulated by high K+ (20 mM) and
      sensitive to a DA agonist. Pergolide (100 microM) reduced both [3H]DA and
      endogenous DA release, while eticlopride (10 microM) increased [3H]DA, but not
      endogenous DA release. The results demonstrate an alternative cheap and quick way
      to study neurotransmitter release from brain in vitro.

PMID- 9253751
TI  - Increased cardiac workload by adrenoceptor agonists for the estimation of
      potential antiischemic activity in a conscious rabbit model.
AB  - The antiischemic effect of drugs can be detected at a lower dose range if the
      cardiac workload is increased. A brief period of frequency-loading (ventricular
      overpacing = VOP) results in well-defined, reproducible changes in cardiac
      parameters in the conscious, chronically instrumented rabbit; however, rapid
      pacing frequently evoked ventricular tachycardia or even fatal ventricular
      fibrillation. Therefore, cardiac workload has been increased by i.v.
      administration of adrenoceptor agonists, such as isoproterenol (ISO),
      phenylephrine (PHE), and their combination, respectively. The doses applied
      (especially the combination of 2 micrograms/kg ISO and 16 micrograms/kg PHE,
      giving optimal changes) were sufficient to produce a marked elevation of both the
      ST segment in the intracavital electrogram and the left ventricular end-diastolic
      pressure, without evoking cardiac arrhythmias. We compared the effect of this
      adrenergic "test" stimulus with that of VOP on hemodynamic and
      electrophysiological parameters of the heart, and furthermore, on the
      modification of responses to both "test" stimuli by oral administration of the
      coronary vasodilator: Isosorbide-5-mononitrate (IS-5-N), given in a dose of 40
      mg/kg. Both VOP- and ISO+PHE-induced changes were significantly attenuated by IS
      5-N, and a temporal coincidence of the maximal effects was found as well. We
      reached the following conclusion: The combined administration of ISO and PHE not
      evoking fatal arrhythmias in the dose range applied can replace the more risky
      VOP as a "test" workload in the estimation of antiischemic action.

PMID- 9253752
TI  - A simple, rapid, and sensitive scintillation proximity assay for the
      determination of levels of guinea-pig interleukin-5 in bronchoalveolar lavage
      samples.
AB  - This article describes the development and validation of a scintillation
      proximity assay (SPA) sensitive for guinea-pig interleukin-5 (IL-5). SPA beads
      were coated with TRFK-5, a monoclonal antibody directed against mouse IL-5, which
      is known also to bind guinea-pig IL-5. The assay is a simple competitive binding
      assay between [125I]-rh-IL-5 and the IL-5, in a sample of guinea-pig
      bronchoalveolar lavage fluid (BALF), for the binding site on the TRFK-5-coated
      beads. IL-5 levels in BALF ([IL-5]BALF) were shown to increase in guinea-pigs
      sensitized to ovalbumin (OvA) and challenged with an OvA inhalation. This
      occurred at a time (24 h) after challenge when there was also a marked
      eosinophilia. The assay was validated by treating guinea-pigs with a second
      antibody, Genzyme 2374-01, directed against IL-5. Treatment with this antibody
      resulted in a significant reduction of the antigen-induced eosinophilia and
      concentration of [IL-5]BALF. This observation confirms that the IL-5 identified
      in BALF also cross-reacts with the antibody Genzyme 2374-01. Interestingly,
      plasma from sensitized, but unchallenged, guinea-pigs also contained detectable
      levels of IL-5, and the stimulation of plasma protein extravasation (PPE) within
      the airways with inhaled histamine also induced a rise in [IL-5]BALF. These
      observations suggest that the plasma may be an additional source of the IL-5
      present in the airways of antigen-challenged guinea-pigs.

PMID- 9253753
TI  - Analysis of agonist-agonist interactions: the crucial influence of curve shape.
AB  - The two-receptor:one-transducer model (Leff, 1987) is here extended to analyze
      interactions between agonists displaying E[A] curves of different shapes, by
      incorporating slope factors into the separate and common parts of the
      transduction pathway. Interactions were modelled as the effect of one agonist, at
      fixed concentration, on the curve to the other. A variety of patterns of position
      and slope changes are predicted. These do not depend on the shape of the control
      curve, rather, they depend on the slope factors in the separate and common
      pathways. The following specific predictions are made: (1) when the common
      pathway is steep, curves undergo potentiation and flattening; (2) when the common
      pathway is flat, curves undergo right-shift and steepening; (3) when the common
      pathway is hyperbolic, curves undergo right-shift, with no slope change; (4) when
      the slope depends on the separate pathways, curves only undergo right-shift with
      no change in slope. The model provides a sound basis for classifying agonist
      interactions and for detecting additional, synergistic or antagonistic
      properties. This analysis indicates that methods based on dose-additivity or
      independence are less reliable for these purposes. The model provides a practical
      test, based on slope changes, to detect and quantify additional properties.

PMID- 9253754
TI  - Two generations of spore research: from father to son.
AB  - Harlyn O. Halvorson has played an active and defining role in the field of
      microbiology for more than 40 years. In this article, he reminisces on the major
      influence that his father, H. Orin Halvorson, had in the direction of his
      professional life. The two H.O. Halvorson's, often confused in the literature,
      became one of the only two father and son pairs to head the American Society for
      Microbiology in 1954 and 1977, respectively. Major scientists of the era, their
      research and their collaborations, are remembered in relation to their main
      works. Harlyn O. Halvorson's interest in bacterial and yeast spores, and
      especially spore germination in bacilli, is the highlight of this memoir. His
      scientific research thrusts, leadership at Marine Biological laboratories, Woods
      Hole, NACSEX (North American-Cuban Scientific Exchange) and elsewhere, his
      dedication to advanced students and numerous other endeavors, both scientific and
      political, are told here.

PMID- 9253755
TI  - Major viral diseases affecting fish aquaculture in Spain.
AB  - The number of viruses isolated from fish has grown in the last few years as a
      reflection of the increasing interest in fish diseases, particularly those
      occurring in aquaculture facilities. Of all the described viruses, only a few are
      considered to be of serious concern and economic importance; they are described
      in this review, drawing special attention to the four families of viruses
      (Birnaviridae, Rhabdoviridae, Iridoviridae and Reoviridae) that have been
      reported in Spanish aquaculture. Infectious pancreatic necrosis virus, a member
      of the first family, is the most spread virus with a prevalence of 39%. Viral
      diseases are untreatable and because effective and safe vaccines for fish are not
      yet commercially available, a great care needs to be exercised when moving fish
      or eggs from one site or country to another. Some fish health control regulations
      have been legislated in Europe and USA.

PMID- 9253756
TI  - Extracellular bacterial mineralization within the context of geomicrobiology.
AB  - In the biosphere, bacteria can function as geochemical agents, promoting the
      dispersion, fractionation and/or concentration of matter. These processes, which
      are being more and more valued from the point of view of various scientific
      disciplines, have given rise to the field of geomicrobiology. At the same time,
      microbial processes resulting in the concentration of matter and thus inducing
      the formation of minerals, constitute an area of research of growing interest
      known as biomineralization. In this review a succinct summary of various aspects
      of both disciplines has been offered together with a more detailed review of
      those aspects related to extracellular bacterial mineralization. The significance
      of the role played by the metabolism of bacteria is discussed along with the
      results of recent research on the role of dead bacteria and bacterial remains
      that act as heterogeneous nuclei of crystallization. The role played by the
      membranes of bacteria has also been considered to be highly relevant, and a
      discussion concerning their possible value as models for both the study of more
      complex biomineralization processes as well as application in the field of
      biomimetic materials is put forward.

PMID- 9253757
TI  - Use of Percoll gradient centrifugation for the isolation of diatoms from Wadden
      Sea sediments; diatom yields, species recoveries and population diversity.
AB  - The technique of Percoll gradient centrifugation was applied to samples from
      Wadden Sea sediments of the shoreside near Dangast (German Bight). Experiments
      were also performed with Wadden Sea sediment inoculated with diatoms and with
      axenic and mixed diatom cultures. For axenic and mixed cultures, total recoveries
      ranged from 6 to 70% of the diatoms loaded onto the gradients, whereas the yields
      were less than 5% in most of the experiments with Wadden Sea sediments. The
      extraction of diatoms from mixed cultures and from sediment samples was not
      quantitative, neither in terms of biodiversity nor of total individuals
      extracted, because the rates of recovery varied for the different species. Diatom
      cells extracted by Percoll gradient centrifugation were devoid of sand grains and
      debris. The obtained material was suitable to be used in biochemical experiments,
      in cultural studies and for electron microscopy. The overall cell morphology and
      subcellular organelle organization was excellent and appeared to be unaffected by
      the purification procedure. The results and advantages and disadvantages of the
      technique are discussed.

PMID- 9253758
TI  - Production of carpophores of Lentinus edodes and Ganoderma lucidum grown on cork
      residues.
AB  - Cork, being widely used in industry, generates high amounts of waste of difficult
      elimination because of its complex biological degradation, and the high pollutant
      smokes from its burning. Similarities between suberin (major component of cork)
      and lignin suggest that fungi with high lignin degrading capacity could colonize
      cork residues. Basidiomycetes such as Lentinus edodes and Ganoderma lucidum,
      besides their capacity for degrading, are edible. Thus, while using them to
      degrade cork, it is also possible to obtain a food product. In this study, dry
      matter was reduced 40%, suberin was degraded 45%, oxidizable carbon was increased
      35%, and Lentinus showed a high rate of growth. These results indicate that there
      is an environmental alternative to the elimination of residues from the cork
      industry.

PMID- 9253759
TI  - Implementation of conditions of the inoculum stage for Streptosporangium
      cultures.
AB  - Different factors concerning the inoculum stage of cultures classified within the
      genus Streptosporangium have been studied. These factors include a comparison
      among several inoculum media and sources, the influence of aeration and volume of
      medium in the growth of the cultures, and the effect of the inoculum size on the
      course of the production of two antibacterial substances. The results suggest
      that a slight variation in the status of the seed culture (age, biomass
      concentration, etc.) affect the course of the batch culture during its initial
      exponential phase (3-5 days), whereas, at longer times, the behavior of the
      culture does not depend greatly on the characteristics of the inoculum. The
      results obtained have allowed to define a set of conditions producing the maximum
      increase of biomass in the minimum time.

PMID- 9253760
TI  - Characterization and selection of lactobacilli isolated from Spanish fermented
      sausages.
AB  - The use of starter cultures to control and run the fermentative process is a
      usual way of manufacturing sausages in meat industries. The first stage in the
      starter culture designing process is to characterize the lactic acid bacteria
      isolated from these meat products, in order to select the best strains. The
      strains used for this study were isolated from different dry fermented sausages,
      obtained during the manufacturing process. The main tests used to identify the
      isolated bacteria were: microscopic-morphologic characteristics, catalase
      activity, production of gas, growth at 8, 15 and 45 degrees C, fermentation of
      carbohydrates and production of lactic acid isomers. A total of 194 strains were
      identified. Lactobacillus sake and Lactobacillus plantarum were the most frequent
      species. Other microbiological tests were also performed, and three strains of
      Lactobacillus sake were found which did not produce dextran from sucrose.

PMID- 9253761
TI  - Growth of methylaminotrophic, acetotrophic and hydrogenotrophic methanogenic
      bacteria on artificial supports.
AB  - The efficiency of organic matter degradation in attached biomass reactors depends
      on the suitable selection of artificial support for the retention of bacterial
      communities. We have studied the growth on glass and clay beads of
      methylaminotrophic, acetotrophic and hydrogenotrophic methanogenic bacterial
      communities isolated from anaerobic reactors. Bacterial counts were performed by
      the standard MPN technique. Experiments were performed in 50 ml vials for 12 days
      at 35 degrees C. Increase in the counts of methylaminotrophic and
      hydrogenotrophic methanogens occurred on both glass and clay beads. The latter
      support material also stimulated the growth rate of methylaminotrophic
      methanogens.

PMID- 9253762
TI  - Gonzalo Vidal (1943-1994). A life for micropaleontology and Precambrianresearch.

PMID- 9253763
TI  - Macrolife and beyond.

PMID- 9253764
TI  - Membrane insertion: The strategies of toxins (review).
AB  - Protein toxins are soluble molecules secreted by pathogenic bacteria which act at
      the plasma membrane or in the cytoplasm of target cells. They must therefore
      interact with a membrane at some point, either to modify its permeability
      properties or to reach the cytoplasm. As a consequence, toxins have the built-in
      capacity to adopt two generally incompatible states: water-soluble and
      transmembrane. Irrespective of their origin or function, the membrane interacting
      domain of most protein toxins seems to have adopted one out of two structural
      strategies to be able to undergo this metamorphosis. In the first group of toxins
      the membrane interacting domain has the structural characteristics of most known
      membrane proteins, i.e. it contains hydrophobic and amphipathic alpha-helices
      long enough to span a membrane. To render this 'membrane protein' water-soluble
      during the initial part of its life the hydrophobic helices are sheltered from
      the solvent by a barrel of amphipathic helices. In the second group of toxins the
      opposite strategy is adopted. The toxin is an intrinsically soluble protein and
      is composed mainly of beta-structure. These toxins manage to become membrane
      proteins by oligomerizing in order to combine amphipathic beta-sheet to generate
      sufficient hydrophobicity for membrane insertion to occur. Toxins from this
      latter group are thought to perforate the lipid bilayer as a beta-barrel such as
      has been described for bacterial porins, and has recently been shown for
      staphylococcal alpha-toxin. The two groups of toxins will be described in detail
      through the presentation of examples. Particular attention will be given to the
      beta-structure toxins, since four new structures have been solved over the past
      year: the staphyloccocal alpha-toxin channel, the anthrax protective antigen
      protoxin, the anthrax protective antigen-soluble heptamer and the CytB protoxin.
      Structural similarities with mammalian proteins implicated in the immune response
      and apoptosis will be discussed. Peptide toxins will not be covered in this
      review.

PMID- 9253765
TI  - Protein kinase C: an example of a calcium-regulated protein binding to membranes
      (review).
AB  - The location of the calcium-binding domain on protein kinase C is being addressed
      by mutational and structural studies. This work can be complemented by detailed
      studies of the properties of the binding of the enzyme to membranes. These
      binding studies have revealed a number of unique pieces of information about the
      properties of Ca(2+)-prompted membrane partitioning, including the fact that
      there is only one Ca(2+)-binding site which regulates the partitioning of the
      enzyme and that this site is located 0.3 nm from the membrane interface.
      Furthermore, the binding of protein kinase C to membranes has been shown to
      enhance the affinity of the enzyme for Ca(2+) by several orders of magnitude. We
      illustrate how contributions of the interactions of proteins with other molecules
      also affect the concentration of calcium required to affect membrane
      partitioning. Only when all of these factors are considered can a quantitative
      description of Ca(2+)-regulated protein binding to membranes be achieved. Thus
      conformational studies, together with classical thermodynamic studies, can
      provide a more detailed understanding of the functional, as well as, the
      structural, properties of amphitropic proteins.

PMID- 9253766
TI  - Gel filtration chromatographic studies of the isolated membrane domain of band 3.
AB  - We have investigated the oligomeric state of the membrane domain of band 3 (MDB3)
      in non-ionic detergent solution using Sepharose CL-4B gel filtration
      chromatography to study the hydrodynamic properties of the protein as a function
      of its concentration. The studies were performed in a C12E9 (polyoxyethylene-9
      lauryl ether) buffer containing phosphatidylcholine and sodium chloride, which
      significantly slow a dilution-induced band 3 conformational change, and an
      associated aggregation process. Under these conditions native MDB3 eluted
      predominantly as a single Gaussian peak with a Stokes radius of 76 +/- 14 A, at
      all protein concentrations studies between 0.2 and 12 microM. This value agrees
      with the calculated Stokes radius (74 A) determined from the crystal structure of
      the MDB3 dimer. The Stokes radius of the MDB3 monomer was obtained experimentally
      by treating native MDB3 with 0.5% SDS, and exchanging the SDS for C12E9 on the
      Sepharose column. SDS-treated MDB3 showed two peaks whose ratio was strongly
      dependent on applied protein concentration. The peak representing the largest
      material had a Stokes radius of 69.7 +/- 14 A, which is essentially the same as
      the native MDB3 dimer. The peak representing the smaller material had a Stokes
      radius of 36 +/- 9 A, and was assigned as the MDB3 monomer in C12E9. Evidence is
      discussed which indicates that the C12E9 monomer specifically self-associates to
      form a functional MDB3 dimer. We conclude that native MDB3 exists as a stable
      dimer in mixed micellar solutions composed of C12E9 and phosphatidylcholine, and
      that the dimer can be dissociated to monomers only by denaturation.

PMID- 9253767
TI  - Heparin binding protein-44 (HBP-44)/receptor-associated protein (RAP)mediates
      cell-substratum adhesion of mouse NIH/3T3 cells through its binding to low
      density lipoprotein (LDL) receptor-related protein (LRP).
AB  - The low density lipoprotein receptor-related protein (LRP) is a multifunctional
      endocytic receptor with the ability to bind and endocytose several structurally
      and functionally distinct ligands. The 39 kDa receptor-associated protein (RAP)
      is an endoplasmic reticulum (ER) resident protein, which is believed to function
      intracellularly as a molecular chaperone for LRP and to regulate its ligand
      binding activity along the secretory pathway. Mouse heparin binding protein-44
      (HBP-44) is a homologue of human RAP. Using a recombinant form of HBP-44
      expressed in Escherichia coli cells as a highly specific ligand for LRP, we
      demonstrated that HBP-44 coated on cell culture plates mediates the cell
      substratum adhesion of mouse 3T3 fibroblasts in a dose-dependent manner, with 50%
      attachment at the concentration of 0.2 micrograms/ml. Ligand blot analysis with
      HBP-44 of whole cell extracts and the materials precipitated by anti-LRP
      antibodies revealed that the receptor for HBP-44 on NIH/3T3 cells was LRP. The
      results suggest that LRP serves as a cell adhesion receptor in some cells.

PMID- 9253768
TI  - Determination of viral neuraminidase specificity for membrane-bound sialic acids
      by cell electrophoresis.
AB  - The ability of the influenza virus neuraminidase (NA) to cleave specific sialic
      acids was measured by cell electrophoresis. Most of the surface charge of human
      erythrocytes can be attributed to sialic acids. Therefore cleavage of sialic
      acids reduces the surface charge density which is measurable as a reduced cell
      electrophoretic mobility (EPM). For experiments specifically sialylated,
      erythrocytes were used. Their EPM was significantly decreased after incubation
      with virus strains possessing the corresponding NA specificity, even when the
      viral haemagglutinin (HA) was unable to bind to the erythrocyte's surface. Thus,
      the limited applicability of elution experiments, which requires virus binding,
      is overcome. An additional advantage of this procedure is that it is non
      radioactive. In our model system the erythrocyte's surface resembles the natural
      situation of viral interaction with membrane-bound receptors.

PMID- 9253771
TI  - Three dimensional image reconstruction of neuroanatomical structures: methods for
      isolation of the cortex, ventricular system, hippocampus, and fornix.
AB  - Magnetic Resonance (MR) imaging allows volumetric quantification of a variety of
      neuroanatomical structures using two dimensional (2D) images as well as three
      dimensional (3D) reconstruction of the brain and any of its constituent parts.
      Three-dimensional analysis permits integration of the neuroanatomical changes
      which occur in pathologic states, with the cognitive and behavioral changes
      elucidated through neuropsychological assessment. This paper describes uniform
      methods for 3D neuroanatomical isolation of the neocortex, ventricular system,
      and hippocampus in both normal and pathologic states. The 3D methods are
      described in detail using two different software programs, ANALYZE and IMAGE.
      Three-dimensional neuroanatomical reconstructions were carried out on a patient
      who sustained a very severe traumatic brain injury. The 3D image analysis in the
      patient with traumatic brain injury, revealed structural changes in frontal and
      temporal cortex, ventricular dilation, and hippocampal atropy. The
      neuropsychological impairments in this patient, were consistent with the observed
      neuroanatomical changes revealed on 3D image reconstruction. This technology
      permits precise determinations of the extent and severity of the neuroanatomical
      changes which follow neurological injury disease.

PMID- 9253770
TI  - Postconcussion symptoms.
AB  - Research pertaining to the self-report of symptoms after traumatic brain injury
      was reviewed. Cognitive, emotional, and motivational factors have more relevance
      than demographic (except for female sex) and personality factors. Specific
      neuropsychological deficits in attention and memory have been found in the early
      stages after head injury of even mild severity. This is unlikely to be the only
      factor affecting symptom persistence. Exaggeration of cognitive dysfunction
      occurs in some cases, but appears unrelated to symptom overreport. Increased
      emotional distress typically accompanies symptom persistence. The psychological
      reaction of preoccupation with symptoms and emotional distress is not unique to
      concussion, but also occurs after severe head injury and back injury and relates
      more to the personal interpretation of the effect of the trauma than to objective
      indicators of brain injury severity.

PMID- 9253772
TI  - [Multiple roles of inducible cyclooxygenase-2 and its selective inhibitors].
AB  - Cyclooxygenase (COX) is the enzyme that catalyzes the conversion of arachidonic
      acid to prostaglandin endoperoxides. In addition to constitutive COX-1, inducible
      COX-2 has been discovered. COX-2 is induced not only in acute exudative rat
      carrageenin-induced pleurisy, but in granuloma formation/proliferative
      inflammation for the acceleration of angiogenesis. This means that COX-2 is
      induced in the healing process of wounds such as in granuloma of gastric ulcer
      and the proliferative stage of endometrium. COX-2 is also introduced in ovulation
      and parturition. Osteoblasts induce COX-2 to accelerate bone absorption.
      Induction of COX-2 in colon carcinoma is a recent, very exciting topic of
      investigation. We can learn about many unknown roles of COX-2 from its knockout
      mouse, but the results must be interpreted cautiously. Development of selective
      COX-2 inhibitors, such as NS-398, opened a new era in which the side effects of
      gastric and renal lesions by NSAIDs could be ignored. However, prolongation of
      would healing by the inhibitors and transient expression of COX-2 must be
      considered in medical intervention with selective COX-2 inhibitors. Nevertheless,
      acute exudative inflammation, granuloma formation and bone absorption in
      rheumatoid arthritis are good targets for these inhibitors and application of
      these inhibitors will be extended to dysmenorrhea, interruption of abortion and
      increasing survival rate of patients with colon carcinoma.

PMID- 9253773
TI  - [Neurotransmission in human brains measured by positron emission tomography
      (PET)].
AB  - Various techniques have been developed to image human brain function in the past
      decade. X-ray computerized tomography and magnetic resonance imaging (MR) are
      used to evaluate brain structure. Recently, positron emission tomography (PET)
      and MR are often utilized to perform human brain mapping such as attention,
      cognition, language comprehension, and so on. PET also makes it possible to
      evaluate the states of various types of neurotransmission. These techniques
      cannot only be used to map "brain neurochemistry" in normal human brains, but
      they will also increase our knowledge by demonstrating neurochemical
      abnormalities in a wide range of neurological and psychiatric disorders or those
      that occur during normal aging. The PET techniques are applicable to the
      development of new drugs in the pharmaceutical industry. Using PET techniques of
      imaging neurotransmission, it is feasible to measure the release of
      neurotransmitter after activation of the CNS by various methods (ligand
      activation study). We have developed the methodology of using 11C-labeled
      antagonists for mapping functional histamine H1-receptors in human brain directly
      and noninvasively by PET. The present review article provides an outline of the
      conceptual and methodological progress over the past several years that has made
      it possible to visualize neurotransmission in human brains by PET.

PMID- 9253769
TI  - The Halstead Category Test: a fifty year perspective.
AB  - The Category Test, a major part of the Halstead-Reitan Neuropsychological
      Battery, was first described in a 1943 article by Halstead and Settlage. This
      paper reviews the development of the test, the psychometric properties of the
      instrument, available administration and scoring methods, discusses various
      interpretative strategies, and the empirical support for the test's clinical
      validity. Recent developments are then reviewed, as well as what the authors see
      as the future potential for this instrument.

PMID- 9253774
TI  - [45Ca kinetics and calcium balance studies. A useful method for analyzing calcium
      movement as a whole throughout the entire body in rats].
AB  - 45Ca kinetics and calcium balance studies allow for the simultaneous
      determination of calcium movement in the intestines, kidneys and bones. Since the
      flow of minerals in each of these organs depends on those in other organs, it is
      important to evaluate calcium movement as a whole throughout the entire body.
      Morphological methods can be used to evaluate local bone formation and resorption
      microscopically within defined windows. However, bone remodeling does not proceed
      equally in every part of the skeleton, and local events tend to be misread as
      general phenomena. Although variables such as bone formation and resorption
      obtained in 45Ca kinetics and calcium balance studies tell nothing about the
      location of these events, and the concept of compartments can be somewhat
      difficult to understand, this method is still useful for obtaining quite reliable
      results compared to those obtained by other methods. Our review describes the
      concept of the compartment model and explains the pertinent methods in comparison
      with other methods.

PMID- 9253775
TI  - [Antihypertensive effects of a novel calcium antagonist, AE0047, in various
      hypertensive models].
AB  - The antihypertensive effects of oral or intravenous administration of AE0047, a
      novel 1,4-dihydropyridine-type calcium antagonist, were investigated in
      spontaneously hypertensive rats (SHR/crj), one kidney-one clip renal hypertensive
      rats (RHR), deoxycorticosterone acetate (DOCA)-salt hypertensive rats (DHR) and
      two kidney-one clip renal hypertensive dogs (RHD). AE0047 (1, 3, 10 mg/kg, p.o.)
      caused a dose-related reduction of systolic blood pressure (SBP) with low reflex
      tachycardia in SHR/crj and RHR. The effect reached its maximum at 2-4 hr after
      administration and was sustained for a long time. In DHR, AE0047 (0.3, 1, 3
      mg/kg, p.o.) similarly showed the antihypertensive effects at 2-7 hr with no
      significant changes in heart rates (HR). The doses (ED30) of AE0047 required to
      decrease SBP by 30% were 2.6, 3.4 and 0.68 mg/kg in SHR/crj, RHR and DHR,
      respectively. In RHD, and AE0047 capsule (GJ-0956: 4, 8, 16, 32 mg/body, p.o.)
      produced dose-dependent and long lasting effects with a transient and slight
      increase in HR. Furthermore, the intravenous administration of AE0047 (10, 30,
      100 micrograms/kg) produced the antihypertensive action slowly, reached a plateau
      10 min later and then maintained for many hours. In contrast, nitrendipine (3-100
      mg/kg, p.o., 3-30 micrograms/kg, i.v.) and nicardipine (1-30 mg/kg, p.o., 3-30
      micrograms/kg, i.v.) exhibited a similar potency to AE0047, but these maximal
      effects were produced at 1-2 hr and 0.5-1 min in the case of oral and intravenous
      administration, respectively, with a rapid recovery in the above hypertensive
      rats. These results indicate that AE0047 exhibits an antihypertensive effect with
      a slow onset and long-lasting profile.

PMID- 9253776
TI  - [Antihypertensive effects of long-term treatment with AE0047, a novel long
      lasting calcium antagonist, in hypertensive models of rats and dogs].
AB  - The antihypertensive effects of AE0047, a novel 1,4-dihydropyridine-type calcium
      antagonist, were investigated in spontaneously hypertensive rats (SHR/crj) and
      two kidney-one clip renal hypertensive dogs (RHD). AE0047, which was orally
      administered at the dose of 0.3, 1 or 3 mg/kg once daily for 8 consecutive weeks
      to SHR/crj, exhibited a dose-related decrease in systolic blood pressure. The
      antihypertensive action was reinforced during the drug treatment at 0.3 and 1
      mg/kg. At each dose, the trough-to-peak (T/P) ratio was above 0.50 two weeks
      later. Although the reflex tachycardia was observed at 1 or 3 mg/kg on the 1st
      day, it gradually weakened within 8 weeks. Long-term treatment with AE0047 led to
      the regression of left ventricular hypertrophy. Furthermore, AE0047 had no
      influences on lipid and glucose metabolism. In RHD, and AE0047 capsule (GJ-0956)
      containing 2 or 8 mg of the drug was administered for 2 weeks. GJ-0956 produced
      no reduction in blood pressure at 2 mg, but enhanced the antihypertensive effect
      starting at 8 mg. The T/P ratios were 0.52 and 0.67 for the systolic and
      diastolic pressure, respectively, on the 14th day. These results indicate that
      AE0047 may be expected to exhibit beneficial effects for the clinical treatment
      of hypertension.

PMID- 9253777
TI  - Susceptibility testing of bacteria and fungi. Report from "the Norwegian Working
      Group on Antibiotics".

PMID- 9253778
TI  - Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results
      of a tripart assessment survey. The Fatigue Coalition.
AB  - Although fatigue is the most common symptom reported by cancer patients and has
      serious adverse effects on quality of life, it remains poorly understood. A
      survey was designed to characterize the epidemiology of cancer-related fatigue
      from the perspectives of the patient, primary caregiver, and oncologist. A
      telephone survey included 419 cancer patients recruited from 100,000 randomly
      selected households nationwide. Patients provided access to 200 primary
      caregivers (usually family members) who were also interviewed by telephone. In a
      separate mail survey, 197 of 600 randomly sampled oncologists (unrelated to the
      patients) responded to a questionnaire that assessed perceptions and attitudes
      concerning fatigue in cancer patients who had received chemotherapy or
      radiotherapy and their caregivers. The median patient age was 65 years, and the
      principal cancer diagnoses were breast (females) and genitourinary (males). Fifty
      nine percent of the patients had received chemotherapy, 63% radiation therapy,
      and 24% both; 20% of patients received their last treatment within 6 weeks, 31%
      within 7 weeks to 1 year, and 49% more than 1 year ago. More than three quarters
      of patients (78%) experienced fatigue (defined as a general feeling of
      debilitating tiredness or loss of energy) during the course of their disease and
      treatment. Thirty-two percent experienced fatigue daily, and 32% reported fatigue
      significantly affected their daily routines. Caregivers reported observing
      fatigue in 86% of the index patients, and oncologists perceived that 76% of their
      patients experienced fatigue. Although oncologists believed that pain adversely
      affected their patients to a greater degree than fatigue (61% v 37%), patients
      felt that fatigue adversely affected their daily lives more than pain (61% v
      19%). Most oncologists (80%) believed fatigue is overlooked or undertreated, and
      most patients (74%) considered fatigue a symptom to be endured. Fifty percent of
      patients did not discuss treatment options with their oncologists, and only 27%
      reported that their oncologists recommended any treatment for fatigue. When used,
      treatments for fatigue were generally perceived by patients and caregivers to be
      successful. These data confirm the high prevalence and adverse impact of cancer
      related fatigue, although it is seldom discussed and infrequently treated. For
      patients and oncologists, improving the quality of life of cancer patients
      requires a heightened awareness of fatigue, a better understanding of its impact,
      and improve communication and familiarity with interventions that can reduce its
      debilitating effects.

PMID- 9253779
TI  - The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: a new tool
      for the assessment of outcomes in cancer anemia and fatigue.
AB  - Anemia, frequently associated with cancer and cancer treatment, can use a variety
      of symptoms that diminish overall quality of life (QOL). Fatigue is the most
      commonly reported symptom among cancer patients and can significantly affect
      their daily lives. Using the Functional Assessment of Cancer Therapy-General
      (FACT-G) instrument, which measures general QOL, as a core questionnaire, 20 new
      questions related to the impact of fatigue and other anemia-related symptoms on
      patients with cancer were developed. Two new instruments were produced: the FACT
      Fatigue (FACT-F), consisting of the FACT-G plus 13 fatigue items (the Fatigue
      Subscale), and the FACT-Anemia (FACT-An), consisting of the FACT-F plus seven
      items addressing other concerns related to anemia, but unrelated to fatigue. FACT
      F and FACT-An demonstrated good stability (r = .87 for both) and strong internal
      consistency (alpha = .95 and .96, respectively). Test-retest reliability
      coefficients for the Fatigue Subscale and nonfatigue items also showed good
      stability (r = .84 to .90), and the Fatigue Subscale showed strong internal
      consistency (alpha = .93 to .95). Convergent and discriminant validity testing
      revealed a significantly positive relationship with other known measures of
      fatigue, a significant negative relationship with vigor, and an anticipated lack
      of relationship with social desirability. The FACT-An, FACT-F, and Fatigue
      Subscale were found to successfully discriminate patients based on hemoglobin
      (Hb) level and Eastern Cooperative Oncology Group (ECOG) performance status. When
      patients were divided into two groups by Hb levels, patients with Hb levels
      greater than 12 g/dL reported significantly less fatigue, fewer nonfatigue anemia
      symptoms, better physical well-being, better functional well-being, and higher
      general QOL. The FACT-An, the FACT-F, and the Fatigue Subscale are useful
      measures of QOL in cancer patients and add focus to the widespread clinical
      problems of anemia and fatigue.

PMID- 9253780
TI  - The impact of epoetin alfa on quality of life during cancer chemotherapy: a fresh
      look at an old problem.
AB  - Untreated anemia is common in cancer patients. Previous studies have demonstrated
      that both the existence of cancer and treatment with chemotherapy can suppress
      the normal endogenous erythropoietic response to anemia, making some cancer
      patients transfusion cadidates. In placebo-controlled phase III studies,
      administration of recombinant human erythropoietin (epoetin alfa) increased
      hemoglobin (Hb) levels and decreased transfusion requirements in patients
      undergoing cancer chemotherapy. In these studies, an increase in self-perceived
      energy level, functional status, and overall quality of life (QOL) was noted in
      the subset of patients in whom hematocrit levels increased by > or = 6%. To
      examine more closely the relationship between epoetin alfa therapy and QOL issues
      in patients undergoing chemotherapy, we conducted an open-label phase IV study
      involving 2,030 patients treated at 570 community cancer centers in the United
      States. Patients initially received epoetin alfa 150 U/kg subcutaneously (s.c.)
      three times per week for 4 months; if response was judged inadequate, the dosage
      was increased after 8 weeks to 300 U/kg s.c. three times per week. Hb levels and
      transfusion requirements were monitored monthly. Before and after the study, each
      patient completed a linear analog self-assessment scale designed to measure
      energy level, daily activity, and overall QOL. During epoetin alfa therapy, there
      was a progressive and significant increase (P < .001) in Hb concentrations.
      Significantly fewer (P < .001) patients were transfused and fewer transfusions
      were administered per patient per month after the first month of epoetin alfa
      therapy. Fifty-eight percent of the patients who required a transfusion during
      the first month of epoetin alfa therapy did not require a transfusion during the
      subsequent 3 months of the study. The entire patient population demonstrated a
      significant increase in mean scores for energy level, daily activity, and overall
      QOL. The magnitude of the increase in these scores correlated with the magnitude
      of the increase in Hb concentration. Statistically significant improvement in
      energy scores, daily activity, and overall QOL (P < .05) were observed,
      regardless of tumor response. These observations require confirmation on placebo
      controlled trials, but the implications for oncology practice are important. They
      suggest that in cancer patients undergoing chemotherapy, the tradition of leaving
      anemia untreated may compromise patients' ability to function and their QOL.

PMID- 9253781
TI  - Impact of transfusion on viral load in human immunodeficiency virus infection.
AB  - Recent research has shown that anemia and transfusion are associated with
      accelerated mortality in patients with human immunodeficiency virus type 1 (HIV
      1) infection. It appears that blood transfusions may directly accelerate HIV-1
      disease progression through activation of HIV-1 expression and/or transfusion
      related immunosuppression. In vitro and in vivo evidence suggests that
      immunization with common recall antigens (eg, tetanus toxoid) can significantly
      increase plasma HIV viremia, as well as the in vitro susceptibility of peripheral
      blood mononuclear cells to acute infection. Allogeneic leukocytes also present an
      antigenic challenge to HIV-infected mononuclear cells, which may cause them to
      proliferate and increase viral production. In vitro incubation of HIV-infected
      mononuclear cells with allogeneic blood components (mainly leukocytes) results in
      increased viral replication. Whether the effects of transfusion on HIV viral load
      are due to a reduced immune response and/or activation of the virus itself
      remains to be determined. An ongoing study is evaluating the effects of depleting
      leukocytes from blood prior to transfusion in HIV-infected patients. Patients are
      randomized to receive standard of leukocyte-depleted red blood cell (RBC)
      transfusions and the effect of transfusion on HIV replication is measured.
      Preliminary data suggest that leukocyte depletion prior to RBC transfusion does
      not alter viral replication compared with standard packed RBC transfusions.

PMID- 9253782
TI  - Allogeneic transfusion and infection: economic and clinical implications.
AB  - An increased incidence of postoperative infection and risk of cancer recurrence
      in patients who have received allogeneic blood transfusions suggests that such
      transfusions may be associated with clinically significant immunomodulatory
      effects. Allogeneic transfusion increase humoral immunity and decrease cell
      mediated immunity. The mechanism of allogeneic transfusion-induced
      immunomodulation may involve altered cytokine regulation with a shift toward a
      type-2 (Th2) immune response. In patients undergoing hip replacement or spine
      surgery, the postoperative infection rate with allogeneic blood transfusion
      appears to be 7- to 10-fold higher than with autologous blood or no transfusion.
      The occurrence of postoperative infection is largely abrogated through the use of
      autologous or leukocyte-depleted blood. In our orthopedic surgery patients, use
      of allogeneic blood was associated with a significantly increased length of
      hospital stay, resource consumption, and attendant hospital charges. Allogeneic,
      but not autologous, blood transfusion were associated in a dose-dependent manner
      with longer hospital stays and higher costs. Multiple linear regression analyses
      demonstrated that the number of units of allogeneic blood transfused, rather than
      surgeon and type of surgery, was the most statistically significant predictor of
      length of stay and hospital charges. Using data reported in the literature, we
      estimate that the death rate from allogeneic transfusion-related postoperative
      infection and cancer recurrence combined (215 deaths with 1% causality to 21,500
      with 100% causality) may exceed the death rate due to all other transfusion risks
      combined. Improved clinical outcomes may result from techniques that minimize
      allogeneic blood use or its immunologic effects (e.g., autologous transfusion or
      other blood-sparing approaches in surgery, leukodepletion of allogeneic blood,
      and the use of growth factors [eg, epoetin alfa]).

PMID- 9253783
TI  - Perioperative epoetin alfa increases red blood cell mass and reduces exposure to
      transfusions: results of randomized clinical trials.
AB  - To avoid the inherent risk of complications associated with perioperative
      allogeneic transfusion, preoperative autologous blood donation (PAD) is
      frequently employed by patients undergoing major elective surgical procedures.
      However, many patients are unable to donate a sufficient quantity of blood prior
      to surgery. Recent studies have shown that epoetin alfa (Procrit; Ortho-Biotech,
      Raritan, NJ) effectively increases red blood cell (RBC) mass when administered
      preoperatively and decreases the requirement for allogeneic transfusion. These
      studies also demonstrated that patients with baseline hemoglobin levels ranging
      from 10 to 13 g/dL have the highest risk for requiring allogeneic transfusions
      and appear to achieve the greatest benefit from epoetin alfa treatment. We
      evaluated several dosing regimens and schedules for perioperative epoetin alfa
      administration. In our initial study, the comparative efficacy of three different
      epoetin alfa regimens was assessed by hemoglobin concentration, hematocrit, and
      absolute reticulocyte counts. In addition, we analyzed the effect of accelerated
      erythropoiesis on iron indices and individual RBC hemoglobin content. Our study
      demonstrated that epoetin alfa is safe and effective in increasing RBC mass;
      however, iron stores considered sufficient for basal erythropoiesis may not
      optimally support the accelerated RBC production associated with epoetin alfa
      therapy. In a subsequent randomized multicenter trial, we compared weekly epoetin
      alfa dosing to daily dosing in patients undergoing elective major orthopedic
      surgery. The results of this study indicated that administering epoetin alfa on a
      weekly schedule for several weeks prior to surgery may be at least as effective
      and more convenient than perioperative daily epoetin alfa dosing.

PMID- 9253784
TI  - Emerging trends in surgical blood transfusion.
AB  - The traditional belief of surgeons that allogeneic blood is an effective and safe
      therapy with minimal risks has been challenged by a heightened awareness of the
      problems of transfusion reactions, disease transmission, and immunomodulation
      related to red blood cell (RBC) transfusion. Surgeons have responded to those
      challenges by reassessing the reasons for transfusion, increasing autologous
      blood use, modifying surgical techniques to reduce blood loss, and employing
      various drugs to reduce transfusion requirements. Of primary importance is the
      need for the surgeon to thoughtfully plan allogenic blood transfusion
      requirements for each patient. Blood should be transfused only when there is a
      documented need to increase oxygen delivery in patients unable to meet demands
      through normal cardiopulmonary mechanisms. Autologous blood use, an alternative
      to allogeneic transfusion, is a standard of care for elective orthopedic
      procedures and radical prostatectomy. Surgical principles of gentle tissue
      handling, anatomic dissection, and blood loss minimization are increasingly
      practiced. Surgical approaches include vascular isolation, use of a water jet
      dissector, microwave tissue coagulation, arthroscopic joint repair, and cold
      compression. Surgical techniques that decrease bleeding morbidity and mortality
      include the transjugular intrahepatic portosystemic shunt, intraluminal stents
      and grafts, laparoscopic techniques, electrocautery, and laser techniques.
      Pharmacologic agents also affect surgical blood loss and transfusion
      requirements. Anesthetic agents, locally acting clotting agents, and
      antifibrinolytics each may reduce blood loss. In addition, perioperative
      recombinant human erythropoietin use significantly decreased the need for
      allogeneic transfusions in both anemic and nonanemic surgical patients. Since
      allogeneic transfusion-induced immunomodulation may have significant effects on
      mortality related to increased rates of postoperative infection and cancer
      recurrence, these new approaches and techniques may have an important clinical
      impact on surgical patients.

PMID- 9253786
TI  - Trends in medical care cost--revisited.
AB  - Market forces have had a greater influence on the health care sector than
      anticipated. The increased use of managed care, particularly HMOs, has been
      largely responsible for a sharp deceleration in the rise of medical care costs.
      After recording double-digit growth for much of the post-Medicare/Medicaid
      period, national health expenditures rose just 5.1 percent and 5.5 percent in
      1994 and 1995, respectively. The medical care Consumer Price Index (CPI) rose 3.5
      percent in 1996-just 0.5 percent above the overall CPI. The delivery and
      financing of health care continues to evolve within a framework of cost
      constraints. As such, mergers, acquisitions and provider alliance groups will
      remain an integral part of the health industry landscape. However, cost savings
      are likely to become more difficult to achieve, especially if the "quality of
      care" issue becomes more pronounced. National health expenditures, which
      surpassed the $1 trillion mark in 1996, are projected to rise to $1.4 trillion by
      the year 2000--representing a 7.2 percent growth rate from 1995. In any event,
      demographics and technological advances suggest that the health sector will
      demand a rising share of economic resources. The ratio of health care
      expenditures to gross domestic product is forecast to rise from 13.6 percent in
      1995 to 15 percent by the year 2000.

PMID- 9253785
TI  - A portrait of Asians and Pacific Islanders in the United States.
AB  - Asians and Pacific Islanders (API) have an increasingly visible presence in the
      United States. This diverse population--encompassing persons with ancestry from
      East and Southeast Asia, the Indian subcontinent, and the Pacific islands--has
      grown at a faster rate than any other major racial or ethnic group. In 1996 Asian
      Americans numbered approximately 9.7 million (up from 3.8 million in 1980),
      nearly 4 percent of the U.S. population. The Census Bureau projects that this
      population group will reach 34.4 million by 2050, representing roughly 9 percent
      of all Americans. While immigration has fueled much of this growth, Asians' young
      age structure also will help boost their numbers in the next century. Fifty-six
      percent of Asian Americans live in three states--California, New York and Hawaii.
      Asian Americans comprise very small proportions of the populations of most other
      states. About 77 percent of the 2.8 million API households in 1996 were families,
      compared with 69 percent of white households. Roughly one in six Asian American
      households has five or more persons, compared with one in 12 white households.
      Educationally, Asians tend to be high achievers--42 percent of all API adults
      have at least a bachelor's degree, compared with 26 percent of while adults. Two
      thirds of Asian Americans participated in the civilian labor force in 1996. Among
      employed Asians, one-third held managerial and professional jobs. Both
      proportions were roughly the same as for whites. Although the median income for
      API households was 9 percent higher than for white households in 1995, this
      difference is largely due to Asian households having more workers contributing to
      the household income. Despite these apparent measures of success, the poverty
      rates for Asian American families and individuals are nearly twice as high as
      those for whites.

PMID- 9253787
TI  - National Survey of Ambulatory Surgery: 1994.
AB  - In 1994, 27.7 million surgical and nonsurgical procedures were performed during
      18.4 million visits to ambulatory surgery settings. Eighty-five percent of the
      ambulatory procedures (23.4 million) were performed in hospital-based settings
      and 15 percent (4.3 million) were in freestanding settings. More than half of the
      ambulatory procedures were in three major categories: operations on the digestive
      system, the eye and the musculoskeletal system. The leading ambulatory procedures
      were extraction of lens (performed almost 2 million times), endoscopy of large
      intestine with or without biopsy (1.8 million) and insertion of prosthetic lens
      (1.6 million). Women had significantly more ambulatory surgery procedures than
      men. The ambulatory procedure performed most frequently on children under 15 was
      myringotomy. Also common for children were tonsillectomies and adenoidectomies.
      For those aged 15-44, frequently performed ambulatory procedures included
      endoscopies of large and small intestine; dilation and curettage of uterus;
      bilateral destruction or occlusion of fallopian tubes; and arthroscopy of knee.
      In the 45-64 year old group, endoscopies of large and small intestine were the
      most commonly performed ambulatory procedures. Extraction of lens and insertion
      of prosthetic lens were the leading ambulatory procedures for those 65 years and
      older, though endoscopies of large and small intestine were also performed
      frequently for this age group.

PMID- 9253788
TI  - Enhanced likelihood of a golden wedding anniversary.
AB  - Today's newly married couples can more than ever expect to celebrate their silver
      and even golden wedding anniversaries. In comparison with their counterparts at
      the turn of the century, the chances of joint survival for 50 years for the
      typical bride and groom in 1995 were 3 1/4 times higher, despite increasing
      divorce rates and due in large part to increasing longevity. Currently, the
      median age at marriage for brides and grooms is at record high levels for both.
      In 1995 the median age at first marriage for a bride was 24.5 years and was 26.9
      years for the groom--at the beginning of the century first marriage vows were
      spoken at age 21.9 and 25.9 years, respectively. The probability of surviving to
      have a silver wedding anniversary is extremely high. Of all newly married couples
      who remain married, nearly 900 out of every 1,000 can anticipate celebrating a
      25th wedding anniversary together.

PMID- 9253789
TI  - Two transcription activation functions in the amino terminus of the mouse
      estrogen receptor that are affected by the carboxy terminus.
AB  - To determine the characteristics of the N-terminal transactivation domain (AF-1)
      of the mouse estrogen receptor (ER), we constructed a number of deletion mutants.
      Wild-type and mutant receptors were expressed in yeast cells and assayed for
      their ability to transactivate an estrogen-responsive reporter plasmid (ERE-CYCl
      LacZ) that contained a single estrogen response element of the vitellogenin A2
      gene promoter. Deletion of the N-terminal 121 amino acids from the mouse ER
      resulted in a 50% reduction in transactivation activity compared with the full
      length wild-type ER. Deletion of the first 150 amino acids resulted in loss of
      90% transactivation activity. An ER deletion mutant lacking residues 121-154
      retained full transcriptional activity, suggesting that this region plays a
      significant transacting role only when the first portion is deleted. A point
      mutation was introduced in the C-terminal region at Met-521 in order to study the
      possible interaction between the C-terminal ligand-binding domain and the N
      terminal AF-1 region. This mutant ER, M521G, exhibited 150% of the
      transcriptional activity of the wild-type ER. An M521G mutant lacking the N
      terminal 121 amino acids retained full transactivation activity, whereas, M521G
      lacking 150 amino acids resulted in only 10% of wild-type activity. These results
      suggest that residues 121-154 might interact with the C terminus to affect
      transcription. In summary, multiple N-terminal regions in the ER were identified
      that function in transactivation. Furthermore, a point mutation in the C-terminal
      portion of the ER may change the conformation of the ER ligand-binding domain,
      producing a more stable receptor/ligand complex that increases transcriptional
      activity. These data suggest that the N- and C-terminal portions of the ER
      interact in a cooperative manner to activate transcription from target genes.

PMID- 9253790
TI  - Studies directed toward a mechanistic evaluation of aromatase inhibition by
      androst-5-ene-7,17-dione. Time-dependent inactivation by the 19-nor and 5 beta, 6
      beta-epoxy derivatives.
AB  - To gain further insight into the mechanism for inactivation of aromatase by
      androst-5-ene-7,17-dione (1) and its 19-nor analog 4, 10 beta-oxygenated steroids
      5 and 6, delta 1(10)-steroid 7, and 19-oxo-5 beta,6 beta-epoxy compound 8 were
      synthesized and tested for their ability to inhibit aromatase in human placental
      microsomes. All of the steroids studied inhibited the enzyme in a competitive
      manner with apparent Ki values ranging from 1.1 to 35 microM. The delta 1(10)
      compound 7 was the most potent inhibitor among them. All of the inhibitors caused
      a time-dependent inactivation of aromatase in the presence of NADPH in air with
      the kinact values ranging from 0.036 to 0.190 min-1. The substrate
      androstenedione protected the inactivation, but a nucleophile, L-cysteine, did
      not, in each case. In contrast, each inhibitor did not cause the time-dependent
      inactivation in the absence of NADPH. These results show that the 5 beta,6 beta
      epoxide 8 and/or the dienone 7 are not a reactive electrophile involved in the
      irreversible binding to the active site of aromatase during the mechanism-based
      inactivation caused by the suicide substrates 1 and/or 4.

PMID- 9253791
TI  - Electrospray mass spectrometry of testosterone esters: potential for use in
      doping control.
AB  - The study described involves an attempt to identify 17 beta-fatty acid esters of
      testosterone in blood plasma following administration of such agents. These drugs
      are therapeutic but are increasingly misused by athletes in an attempt to improve
      sports performance. The mass spectral properties of testosterone esters under
      electrospray ionization are described. These esters (testosterone acetate,
      propionate, isocaproate, benzoate, enanthate, cypionate, phenylpropionate,
      decanoate, and undecanoate) essentially give only a protonated molecular ion
      (MH+) under "optimum sensitivity" mass spectrometric conditions but could be
      induced to fragment in the source or collision cell of a triple quadrupole mass
      spectrometer. The underivatized steroid esters were analyzed by direct infusion
      because development of solvent systems compatible with high-performance liquid
      chromatography (HPLC) was not achieved for these nonpolar compounds. HPLC/MS
      (mass spectrometry) was possible when the steroids were converted to polar, water
      soluble, Girard hydrazones, and almost all were separated by microbore C4 HPLC
      using a water, acetonitrile, TFA gradient. The mass spectra under optimal
      ionization conditions essentially comprised only a molecular ion (M+), but source
      fragmentation gave major ions at M - 59 and M - 87 for all compounds. The
      molecular ion and these fragment ions were monitored in a selected-ion-recording
      (SIR) method developed for detecting the steroids in plasma. Using this
      methodology, testosterone enanthate and undecanoate could be detected after
      intramuscular injection or oral administration of the drugs. Further development
      of the technique could form the basis of a protocol for confirming the misuse of
      testosterone in sport, especially if sensitivity could be improved.

PMID- 9253792
TI  - Structure-activity relationship studies of the amide functionality in (p-O
      sulfamoyl)-N-alkanoyl tyramines as estrone sulfatase inhibitors.
AB  - Recently, we reported the synthesis and biomedical studies of a series of (p-O
      sulfamoyl)-N-alkanoyl tyramines as nonsteroidal estrone sulfatase inhibitors. One
      of the most potent inhibitors in this series is (p-O-sulfamoyl)-N-tridecanoyl
      tyramine 1 with an 1C50 value of 61.3 nM. In this study, we synthesized four
      analogs of 1 (compounds 2-5) to investigate the structure-activity relationships
      of the amide functionality in (p-O-sulfamoyl)-N-tridecanoyl tyramine. Replacement
      of the amide functionality in 1 with an ethylene moiety to form the alkyl analog
      5 resulted in complete loss of sulfatase inhibitory activity (IC50 of 61.3 nM vs.
      > 20 microM). The keto, hydroxy, and ester analogs (inhibitors 2-4) are 8-15
      times less in affinity to the sulfatase than inhibitor 1. However, their
      inhibitory activities are significantly higher than the alkyl analog 5. The
      results suggest that the amide functionality is favorable for sulfatase
      inhibitory activity and that there may be a hydrogen bonding component to the
      enzyme interaction in this region.

PMID- 9253793
TI  - Electrical permeabilization of rat luteal cells: in situ phosphorylation of
      endogenous protein.
AB  - Progesterone synthesis in the corpus luteum is regulated primarily by luteinizing
      hormone which acts via the adenylate cyclase/cyclic AMP/protein kinase A
      signalling cascade. Protein phosphorylation therefore plays a key role in the
      regulation of steroidogenesis, but there are relatively few studies of the in
      situ phosphorylation of luteal cell substrates. This may in part reflect the
      difficulties inherent in measuring changes in protein phosphorylation in intact
      cells preloaded with 32P and difficulties in interpreting data obtained using
      broken cell preparations. We have now applied a method of stable permeabilization
      of luteal cell plasma membranes by exposure of cell populations to a high
      intensity electric field. Under optimum conditions (5 kV/cm, six discharges)
      electrical permeabilization reproducibly produced populations of luteal cells in
      which 70-80% of the cells were permeabilized, as assessed by Trypan blue
      exclusion and [14C] sucrose space measurements. Pores were stable for at least 1
      h, and there were no ultrastructural changes to the cells that could be detected
      by transmission electron microscopy. Permeabilized cells showed rapid cyclic AMP
      induced changes in phosphorylation of endogenous proteins when provided with
      [gamma - 32 P] ATP. Our results demonstrate that the electricity permeabilized
      luteal cell offers a useful model for studying intracellular events in
      steroidogenic stimulus-response coupling cascades.

PMID- 9253794
TI  - Synthesis of sodium androst-5-ene-17-one-3 beta-methylene sulfonate.
AB  - The synthesis of sodium androst-5-ene-17-one-3 beta-methylene sulfonate 2, a
      stable analog of memory-enhancing neurosteroid dehydroepiandrosterone sulfate, is
      described. The synthesis of compound 2 is carried out in six steps from
      dehydroepiandrosterone.

PMID- 9253795
TI  - Synthesis and in vitro evaluation of side chain-unsaturated analogs of 24a,24b
      dihomo-1,25-dihydroxycholecalciferol.
AB  - A synthesis and an in vitro evaluation of side chain-unsaturated analogs 3 and 4
      of 24a, 24b-dihomo-1,25-dihydroxycholecalciferol (1) are described, Novel C23a,
      24-vitamin D synthons (sulfone 10 and aldehyde 11) were used for the synthesis of
      analog 4 and for the efficient preparation of the parent compound 1. The
      synthetic approach developed allows the use of easily available side chain
      fragments, such as oxirane 12 or Wittig reagent 15 for the preparation of
      compound 1 and analog 4, respectively. Introduction of a 24aE double bond results
      in a selective, 1000-fold increase in the binding affinity of analog 4 for the
      vitamin D receptor, compared to the affinity of 1, whereas the affinity of 4 for
      the vitamin D-binding protein and the activity in stimulating the differentiation
      of human promyelocytic leukemia HL-60 cells remained largely unchanged.

PMID- 9253796
TI  - Low extracellular calcium enhances beta cell sensitivity to the stimulatory
      influence of 1,25-dihydroxyvitamin D3 on insulin release by islets from vitamin
      D3-deficient rats.
AB  - The beneficial effect of 1,25-dihydroxyvitamin D3 [1,25 (OH)2 D3] on insulin
      secretion from beta cells in hypocalcemic vitamin D3-deficient rats is now well
      established. Moreover, few data concerning the mechanism of 1,25 (OH) 2D3
      efficiency as a function of the severity of hypocalcemia. In the present
      experiment, we submitted islets from vitamin D3-deficient rats to in vitro
      exposure to a range of decreasing extracellular Ca2+ concentrations ([Ca2+]ex),
      from 0.5 mM to 0.6 mM, during a 6-h 10-8 M 1,25 (OH) 2D3 induction. Thereafter,
      we compared the effect of this pretreatment on the islets' insulin response to a
      given stimulus. Various stimuli were used, and we measured in parallel the
      variations of 86Rb+ and 45Ca2+ efflux and insulin release into the perifusion
      medium. In the presence of 1,25 (OH) 2D3, we observed an inverse correlation
      between the [Ca2+]ex pre-exposure and the amplitude of the insulin response to
      certain stimuli studied, suggesting that beta cells that were pre-exposed to low
      [Ca2+]ex became more sensitive to the beneficial effect of 1,25 (OH) 2D3 on
      insulin release. This effect was observed when beta cells were activated by
      acetylcholine but only during its second phase of stimulation, and more
      particularly with the barium plus theophylline stimulus. In contrast, insulin
      release was not affected by [Ca2+]ex pre-exposure during 1,25 (OH) 2D3 induction
      in response to acetylcholine during its first phase of stimulation, thus
      excluding any mechanism mediated via nutrient pathways, membrane depolarization,
      or inositol triphosphate (IP3)-dependent events. Moreover, the islets that were
      pre-exposed to a 10-fold [Ca2+]ex exhibited only a 50% lower 45Ca2+ content after
      45Ca2+ loading, suggesting a different or relatively more efficient storage
      capacity in the presence of low extracellular calcium. Studies of 45Ca2+ efflux
      showed that the mobilization of Ca2+ stores induced by a barium plus theophylline
      stimulus, in the absence of calcium in the perifusion medium, was more efficient
      in islets pre-exposed to low [Ca2+]ex, whereas the acetylcholine-IP 3-induced
      mobilization of Ca2+ from reticular stores was not affected. These results
      generated the hypothesis that 1,25 (OH)2D3 may prepare the beta cells during
      their pre-exposure to low [Ca2+]ex to become more efficient as concerns insulin
      release via a more efficient mobilization of 45Ca2+ stores (mitochondrial?) and
      by an activation of release potentiating systems via protein kinase C protein
      kinase A pathways.

PMID- 9253797
TI  - Pharmacological approaches and strategies for therapeutic modulation of
      fibrinogen.

PMID- 9253798
TI  - Thrombin receptor: a novel target for antiplatelet drug development.

PMID- 9253799
TI  - Current status of platelet NO synthases.

PMID- 9253800
TI  - New families with von Willebrand disease type 2M (Vicenza).
AB  - The variant von Willebrand disease (vWd) variant type 2M (Vicenza) was identified
      in 13 patients of 7 unrelated families. 11 patients were from different parts of
      germany and 2 patients from Turkey. Hitherto this variant of vWd has been
      described only in two families originating from the province of Vicenza in
      Northern Italy. Characteristically this type of vWd shows the supranormal
      multimers of von Willebrand factor (vWf) in plasma similar to those seen in
      normal plasma after desmopressin infusion. Clinically, the patients present with
      bleeding symptoms. Other laboratory abnormalities include reduced values for vWf
      antigen (vWf: Ag), factor VIII coagulant activity (VII:C), ristocetin cofactor
      activity (RiCof) and collagen binding activity (vWf: CBA). The hereditary
      transmission of this variant is consistent with an autosomal dominant mode of
      inheritance. The patients with vWd type 2M (Vicenza) could be allocated into two
      subgroups: type "platelet normal" with normal vWf properties in platelets and
      type "platelet low" with reduced vWf: Ag levels in platelets.

PMID- 9253801
TI  - The activation of human platelets mediated by two monoclonal antibodies raised
      against CD9.
AB  - The platelet activation induced by two anti-human platelet P24/CD9 McAbs was
      investigated. The results showed that: the pathway of platelet aggregation
      induced by the two McAbs (HI117 and SJ9A4) is not the same; HI117 and SJ9A4
      induced the phosphorylation of platelet proteins (40KD and 20KD) when platelets
      were activated; but HI117 didn't cause a rise in intracellular Ca2+ concentration
      in activated platelets compared with SJ9A4; the epitope recognized by HI117 and
      SJ9A4 is different and this is probably the real reason why the two CD9 McAbs
      play different roles in platelet activation. Additionally McAbs HI117 and SJ9A4
      could not promote associates of other proteins (e.g.: GPIIb/IIIa) with P24/CD9 on
      activated human platelets. All these results indicate that the mechanism of
      platelet activation induced by HI117 or SJ9A4 is different form each other. It
      suggests that CD9 antigen play an important and complex role in platelet
      activation.

PMID- 9253802
TI  - Effect of L-arginine on in vitro plasmin-generation and fibrinogenolysis.
AB  - L-arginine ahs received much attention in numerous aspects of the regulation of
      vascular tone and haemostasis. L-arginine seems to be capable to bind to
      plasminogen, too. The aim of the present paper is to investigate the action of L
      arginine on in vitro plasmin generation and fibrino(geno)lysis by chromogenic,
      kinetic plasmin generation assay and electrophoretic analysis. The acceleration
      of tPA-induced plasmin generation in the presence of low concentration of L
      arginine, along with augmentation of in vitro fibrinogenolysis have been
      documented. L-arginine may have a role in the modification of fibrinogenolysis,
      and this role should be considered if arginine is used as an element of some
      novel antithrombotic agents.

PMID- 9253803
TI  - Lonomia achelous caterpillar venom (LACV) selectively inactivates blood clotting
      factor XIII.
AB  - Lonomia Achelous Caterpillar Venom (LACV) causes a severe acquired bleeding
      diathesis in exposed persons. The condition is characterized by prolonged
      bleeding from superficial wounds and mucous membranes. Intracranial or intra
      abdominal hemorrhage is a common and often fatal complication. A constant finding
      in these cases is a profound decrease of clotting Factor XIII (FXIII) activity.
      In the present study, the effects of LACV on plasmatic and purified human FXIII
      has been evaluated. The results show that native LACV and one of its
      chromatographically purified fractions (termed FIID) produce a dose dependent
      decrease of FXIII activity accompanied with an impairment of fibrin(ogen)
      crosslinking. We conclude that the inactivation of FXIII by fraction FIID (which
      will be named Lonomin V), is one of the principal patho-physiological mechanisms
      behind the acquired bleeding diathesis seen in these cases.

PMID- 9253804
TI  - Microplate reader--a convenient tool in studies of blood coagulation.
AB  - Results of platelet aggregation measured with a dual channel aggregometer and
      with a microplate reader are compared. Platelets in plasma were activated by ADP
      and by collagen, and thrombin was used for the aggregation study of gel filtered
      platelets. The results obtained with both instruments were quantitatively and
      qualitatively similar. A microplate reader allowed a simultaneous measurement of
      a high number of samples with a high degree of reproducibility. The same
      instrument can be useful in other coagulology studies. Results of citrated plasma
      clotting by thrombin or by recalcination together with results of platelet
      counting, both obtained with a microplate reader, are presented in this report as
      well.

PMID- 9253805
TI  - Sulfated polysaccharide from the leaves of Artemisia Princeps activates heparin
      cofactor II independently of the Lys173 and Arg189 residues of heparin cofactor
      II.
AB  - A sulfated polysaccharide (AFE-HCD) purified from the leaves of Artemisia
      princeps Pamp selectively accelerated the rate of thrombin inhibition by heparin
      cofactor II (HCII). By using plasma derived HCII and bacterial expressed
      recombinant HCII molecules, the interaction between each HCII molecule and AFE
      HCD was analyzed. AFE-HCD accelerated thrombin inhibition by plasma derived HCII
      or bacterial expressed wild type HCII to the same extent (IC50: 0.056
      micrograms/ml for plasma derived HCII and 0.066 micrograms/ml for recombinant
      HCII under the experimental condition). The recombinant HCII (rHCII) molecule
      with Lys173-->Leu or Arg189-->His substitution, which is defective in
      interactions with heparin and dermatan sulfate, respectively, is activated by AFE
      HCD to inhibit thrombin in a manner similar to wild type rHCII. These results
      suggested that activation of HCII was independent of its Lys173 or Arg189
      residue. Although AFE-HCD is a selective activator of HCII like dermatan sulfate,
      the amino acid residue required for the activation of HCII was distinct form that
      of dermatan sulfate as well as heparin.

PMID- 9253806
TI  - Comparison of the anticoagulant action of sulfated and phosphorylated
      polysaccharides.
AB  - Oat spelts xylan (OSX), fucoidan, kappa carrageenan and chondroitin sulfates A
      and C were sulfated using chlorosulfonic acid-pyridine complex while the first
      three were phosphorylated using methane sulfonic acid-phosphorous pentoxide
      mixture. The compounds were isolated as the sodium salts and their in vitro
      anticoagulant properties were determined by measuring the concentration of each
      compound required to double prothrombin time of pooled normal human plasma. The
      results of 31P-nmr spectroscopy showed that phosphorylation significantly
      increased the molecular weights of the polysaccharides by forming phosphodiester
      and diphosphodiester bonds. In general the anticoagulant properties of the
      sulfated polysaccharides were related to the % sulfate while the phosphorylated
      polysaccharides showed increases in anticoagulant properties which were related
      to the increase in the molecular weight and inversely related to the % phosphate.
      The mechanism of action of oat spelts xylan phosphate (OSXP) was studied using
      125I-thrombin and normal human plasma. The results showed that at lower
      concentration of the OSXP, the complexation of 125I-thrombin with heparin
      cofactor-II(HC-II) was enhanced, while at higher concentration of the compound,
      the complexation with both antithrombin-III(AT-III) and HC-II was enhanced.

PMID- 9253807
TI  - High and constant plasma levels of tissue plasminogen activator and PEG-hirudin
      can be achieved by subcutaneous delivery.
AB  - Intramural thrombosis is a consistent finding in the arteries of patients who die
      following coronary angioplasty. This thrombosis is thought to have a role in
      restenosis, which is a common complication of coronary angioplasty. It has been
      hypothesised that antithrombotics such as hirudin or tissue-type plasminogen
      activator (tPA), may be therapeutically useful following angioplasty. This report
      describes the bioavailability of both agents following subcutaneous (sc)
      injection in cholesterol-fed rabbits. Intravenously delivered tPA has a half-life
      of 3-5 minutes. The half-life of intravenously administered hirudin is less than
      one hour in many species. In order to prolong the duration of action recombinant
      hirudin was conjugated to polyethylene glycol (PEG). Polyethylene glycol
      conjugated recombinant hirudin (PEG-rH) (0.7 mg/kg) antigen and activity were
      measurable after just 1 hr, reaching a maximum (663 and 884 ng/ml respectively)
      at 12 hours. Significant levels were present in rabbit plasma 24 hours after
      injection. Subcutaneously delivered recombinant (r-tPA) (1 mg/kg) was present in
      significant amounts 1 hr after injection, reaching a maximum (92 IU/ml) at 2
      hours. Levels of tPA at 9 hours were approximately 80x normal circulating levels.
      High and constant levels of functional activity of both PEG-rH and r-tPA in
      rabbit plasma are achieved by subcutaneous delivery.

PMID- 9253808
TI  - Studies of the t-PA-catalyzed Glu-plasminogen activation on different models of
      polymeric fibrin.
AB  - The rate of activation of Glu-plasminogen by t-PA on fibrin clot and on the
      complexes of fibrinogen, its fragment X2, fibrin fragment D-D with N-DSK of
      fibrin has been studied. The reaction rate constant of (kcat/Km) increased and Km
      decreased in series of effectors X2-->X2 - N-DSK-->D-D-->D-D - N-DSK = fibrinogen
      - N-DSK-->fibrin clots. The structure of activator complexes of reaction of Glu
      plasminogen activation by t-PA on fibrin clot has been suggested.

PMID- 9253809
TI  - Effect of evening primrose oil on platelet aggregation in rabbits fed an
      atherogenic diet.
AB  - Evening primrose oil (Oenothera biennis) is a rich source of omega-6 series fatty
      acids. We report here the effects of dietary supplementation with evening
      primrose oil (EPO) on platelet aggregation as the main factor in arterial
      thrombus formation in an experimental model of atherogenesis in rabbits. A total
      of 40 male white New Zealand rabbits were divided into four groups (n = 10
      animals/group): 1: normal diet, 2: atherogenic diet (ATD), 3: normal diet
      enriched with 15% EPO, 4: ATD + EPO. Each group was kept on the diet for 6 weeks.
      We determined serum lipid profile, platelet aggregation in whole blood, platelet
      thromboxane B2 production and platelet lipid peroxides. The atherogenic diet
      increased platelet aggregation (135% when ADP was used, and 185% when collagen
      was used as the inducer). Evening primrose oil reduced hyperaggregation to the
      values obtained in rabbits fed with the normal diet. Thromboxane synthesis was
      increased from 0.18 to 2.28 nmol/10(9) platelets); EPO reduced this value to 1.38
      nmol/10(9) platelets. Lipid peroxides were increased by ATD from 0.27 to 0.81
      nmol/10(8) platelets; EPO prevented this increase (0.35 nmol/10(8) platelets). In
      conclusion, EPO reduced platelet hyperaggregability in rabbits fed an atherogenic
      diet.

PMID- 9253810
TI  - Influence of different anticoagulants on platelet aggregation in whole blood; a
      comparison between citrate, low molecular mass heparin and hirudin.
AB  - Anticoagulants used for platelet function studies in vitro may affect platelet
      responsiveness. In the present study we compared the influence of three different
      anticoagulants, sodium citrate, low molecular mass heparin, and recombinant
      hirudin, on platelet aggregation in whole blood in vitro, using impedance
      aggregometry. ADP and collagen induced aggregation was significantly lower in
      citrated blood compared to hirudin treated blood, reflecting the importance of
      extracellular calcium for platelet function. Inhibition of platelet aggregation
      by aspirin, was more pronounced in citrated blood compared to hirudin treated
      blood, in agreement with the concept of artifactually enhanced thromboxane
      generation in media containing low extracellular calcium levels. In blood
      anticoagulated with low molecular mass heparin, platelet aggregation to collagen
      tended to be enhanced as compared to hirudin treated blood, whereas platelet
      responses to ADP at a high concentration were slightly reduced. Of the
      anticoagulants investigated, the selective thrombin inhibitor hirudin is the most
      suitable anticoagulant for studies of platelet aggregation in vitro in whole
      blood.

PMID- 9253811
TI  - Comparison of four commercial citrate blood collection systems for platelet
      function analysis by the PFA-100 system.

PMID- 9253812
TI  - Carotid plaque typing by multiple-parameter ultrasonic tissue characterization.
AB  - We evaluated the ability of ultrasonic tissue characterization (UTC), based on
      backscattered echo signals, to distinguish among the components of advanced
      carotid plaques. We performed spectral analysis of echo signals acquired from
      human carotid endarterectomy specimens in vitro to calculate three parameters of
      the calibrated power spectrum: slope, intercept and total power for fibrous,
      lipid pool and thrombus constituents of plaque. Plaque constituents were
      identified histologically. We evaluated classification efficacy by discriminant
      function analysis. Slope and intercept parameters alone provided correct
      classification in 92.5%, 57.6% and 72.4% of fibrous, lipid pool and thrombus
      plaque components, respectively. Slope, intercept and total power used in
      combination improved classification of the three tissue types to 93.0%, 69.7% and
      81.0%. The overall proportion of correctly classified tissue regions increased
      from 84.5% to 88.0% by the combined use of the three parameters. The improvement
      in classification that occurred when we included total power as a third parameter
      suggests that ultrasound plaque components may not consist solely of small,
      randomly distributed isotropic scatterers. Our ability to identify plaque thrombi
      provides motivation for future studies of parameter-based imaging methods for
      identifying such plaque that presents an increased risk of embolic neurologic
      ischemic events.

PMID- 9253813
TI  - Automatic attenuation compensation for ultrasonic imaging.
AB  - A new method has been developed for the automatic correction for attenuation in
      ultrasonic pulse-echo imaging. By assuming that a specified relationship holds
      between local attenuation and local backscatter throughout each pulse-echo
      signal, a gain factor may be calculated that more appropriately compensates for
      attenuation at every depth. The rationale depends on the observation that,
      broadly speaking, materials that backscatter strongly also attenuate strongly.
      The new method has been evaluated by postprocessing clinical B-scans following
      video frame capture. The images formed demonstrated the success of the algorithm
      in imaging homogeneous tissues at a constant grey level, irrespective of
      variations in the attenuation of overlying tissue. For example, the fetal lung
      was imaged uniformly irrespective of the presence of rib or spine, and prostatic
      tissue was imaged uniformly through a partial bladder window. Spatial resolution
      and speckle patterns are retained. The method is suitable for real-time
      application.

PMID- 9253814
TI  - Interactive automatic fetal head measurements from ultrasound images using
      multimedia computer technology.
AB  - We have developed a tool to automatically detect inner and outer skull boundaries
      of a fetal head in ultrasound images. These boundaries are used to measure
      biparietal diameter (BPD) and head circumference (HC). The algorithm is based on
      active contour models and takes 32 s on a Sun SparcStation 20/71. A high
      performance desktop multimedia system called MediaStation 5000 (MS5000) is used
      as a model for our future ultrasound subsystem. On the MS5000, the optimized
      implementation of this algorithm takes 248 ms. The difference (between the
      computer-measured values on MS5000 and the gold standard) for BPD and HC was
      1.43% (sigma = 1.00%) and 1.96% (sigma = 1.96%), respectively. According to our
      data analysis, no significant differences exist in the BPD and HC measurements
      made on the MS5000 and those measurements made on the Sun SparcStation 20/71.
      Reduction in the overall execution time from 32 s to 248 ms will help making this
      algorithm a practical ultrasound tool for sonographers.

PMID- 9253815
TI  - Intra- and extrahepatic arterial resistances in chronic hepatitis and liver
      cirrhosis.
AB  - Thirty patients with chronic hepatitis (CH), 84 with liver cirrhosis (LC) and 42
      controls, underwent noninvasive measurement of hepatic artery resistance index
      (RI) by means of Doppler ultrasound (US), at the porta hepatis and in the
      intrahepatic branches, in order to investigate possible changes related to: (a)
      the liver disease; (b) the site of measurement; and (c) ageing. The intrahepatic
      RI differed among LC, CH and controls (0.731, 0.690 and 0.643, p < 0.05), whereas
      the RI at the porta hepatis did not (0.754, 0.748 and 0.729, respectively).
      Intrahepatic RI correlated with age in LC (r = 0.51, p < 0.0001) and in controls
      (r = 0.49, p < 0.001). In LC, it correlated also with the presence and size of
      esophageal varices (r = 0.32, p < 0.05). In conclusion, an increase of hepatic
      artery RI in chronic liver diseases can be demonstrated when assessed in the
      intraparenchymal branches. The increase of hepatic artery RI with ageing should
      be considered in future studies.

PMID- 9253816
TI  - Neural network analysis of Doppler ultrasound blood flow signals: a pilot study.
AB  - It has been hypothesised that each artery in the human body has its own
      characteristic "signature" -a unique Doppler flow profile which can identify the
      artery and which may also be modified by the presence of disease. To test this
      hypothesis an artificial neural network (ANN) was trained to recognise three
      groups of maximum frequency envelopes derived from Doppler ultrasound
      spectrograms; these were the common carotid, common femoral and popliteal
      arteries. Data were collected from 24 subjects known to have no significant
      atheromatous disease. The maximum frequency envelopes were used to create sets of
      training and testing vectors for a backpropagation ANN. The ANN demonstrated a
      high success rate for appropriate classification of the test vectors: 100% for
      the carotid; 92% for the femoral; and 96% for the popliteal artery. This work has
      demonstrated the ability of the ANN to differentiate accurately between different
      and similar flow profiles, outlining the potential of this technology to identify
      subtle changes induced by the onset of arterial disease within a specific vessel.
      It should be noted that the ANN not only models the maximum frequency envelope
      but also, unlike standard indices, makes a decision as to which artery the
      maximum frequency envelope belongs to, thus providing the potential to obviate
      human subjective classification.

PMID- 9253817
TI  - Correlation of ultrasonic attenuation (30 to 50 MHz and constituents of
      atherosclerotic plaque.
AB  - The ultrasonic integrated attenuation and the slope of attenuation (30-50 MHz)
      were measured in vitro at 20 degrees +/- 2 degrees C using radio frequency
      signals backscattered from human aortae. Ultrasonic measurements and histologic
      classifications were made in a total of 124 local regions from 58 independent
      segments of aortae. Values of the integrated attenuation were significantly
      higher in collagen-lipidic (142 +/- 51 dB cm-1, n = 18), and lipidic regions (139
      +/- 53 dB cm-1, n = 11) compared to regions of normal media (97 +/- 20 dB cm-1, n
      = 44) and dense collagen (107 +/- 33 dB cm-1, n = 43). The most elevated
      integrated attenuation values were observed in calcified regions (245 +/- 93 dB
      cm-1, n = 8). The slope of attenuation was significantly higher in lipidic than
      in normal media (p = 0.002), dense collagen (p = 0.0007) or collagenlipidic (p =
      0.04) regions. The correlation between attenuation and local tissue composition
      was used to establish ranges of values of integrated attenuation that are most
      likely to indicate specific tissue types. Images of the local tissue type were
      constructed. Comparison of these quantitative images with the corresponding
      histologic sections demonstrates that attenuation measurements offer promise for
      the in vivo characterization of plaque structure and composition.

PMID- 9253818
TI  - Ultrasound contrast agent in intravascular echography: an in vitro study.
AB  - The intravascular ultrasound image of the intraluminal contour depends on the
      difference between acoustic impedances of the media which create the endoluminal
      interface. There are several limitations to the visualization and detection of
      this interface. These limitations are due to artifacts encountered during image
      formation and to anatomical complexity. The purpose of this study is to obtain
      intraluminal contour enhancement using ultrasound contrast agent (UCA).
      Therefore, our objective was to address the feasibility of this technique by
      documenting the following: (i) the acoustic properties of UCA at 30 MHz; (ii) in
      vitro experimentation with tube or postnecrotic artery; and (iii) suitable
      digital processing. The images obtained with UCA (enhanced image quality) and
      subtracted from those without UCA provided, after simple digital processing,
      accurate visualization of the arterial lumen. The image obtained exhibits an
      even, high-contrast intraluminal edge. Such characteristics facilitate contour
      extraction by the automated contour detection procedures.

PMID- 9253819
TI  - Gray scale second harmonic imaging of the liver: a preliminary animal study.
AB  - Gray scale second harmonic imaging (2.5 MHz/5.0 MHz) was evaluated in preliminary
      animal studies with a new ultrasound contrast agent (FS069). FS069 was
      administered intravenously in 10 rabbits (6 with normal liver, and 4 with
      implanted VX-2 tumors) and two woodchucks with hepatocellular carcinomas. The
      vasculature (including tumor vessels) and liver parenchyma were clearly enhanced
      at a low dosage (optimal dose was from 0.1 to 0.2 mL/kg) in all cases.
      Enhancement was reproducible and generally dose-dependent. Tumors were enhanced
      well during the early phase and tumor enhancement disappeared earlier than that
      of surrounding normal liver. Arterial phase and portal phase were easily
      distinguished and patterns of enhancement were diagnostic of the tumors. Gray
      scale second harmonic imaging is useful in the detection of hepatic tumors and in
      diagnosis of their hemodynamics.

PMID- 9253820
TI  - Analysis of the frequency modulation present in Doppler ultrasound signals may
      allow differentiation between particulate and gaseous cerebral emboli.
AB  - The purpose of this study was to investigate the incidence of frequency
      modulation in Doppler signals from cerebral emboli and to seek possible
      explanations for its occurrence. Signals from 200 particulate emboli and 200
      presumed gaseous emboli were studies. The Doppler signals were visualised in the
      time domain and were classified into three main types. Type I signals contained
      no modulation, type II signals showed gradual frequency changes and type III
      showed a rapid change evident in only a small percentage of the entire signal.
      Type I signals were observed from 71.5% of particulate emboli but only 19% of
      gaseous emboli (X(2)) = 111, p < 0.001). Type II signals were found in 28.5% of
      particulate emboli and 38% of gaseous emboli (X(2)) = 4.06, p < 0.05). The most
      surprising and significant finding was that 43% of gaseous embolic signals were
      categorised as type III signals compared with 0% of signals from particulate
      emboli (X(2)) = 109, p < 0.001). The finding that known particulate emboli appear
      never to produce rapid frequency modulation may provide a basis for
      differentiating between gaseous and particulate emboli.

PMID- 9253821
TI  - Intravascular elasticity imaging using ultrasound: feasibility studies in
      phantoms.
AB  - A technique is described for measuring the local hardness of the vessel wall and
      atheroma using intravascular ultrasound. Strain images were constructed using the
      relative local displacements, which are estimated from the time shifts between
      gated echo signals acquired at two levels of intravascular pressure. Time shifts
      were estimated using one-dimensional correlation with bandlimited interpolation
      around the peak. Tissue-mimicking phantoms with typical morphology and hardness
      topology of some atherosclerotic vessels were constructed. Hard and soft regions
      could be distinguished on the strain image, independently of their contrast in
      echogenicity. Thus, the potential of ultrasonic hardness imaging to provide
      information that may be unavailable from the echogram alone was demonstrated. The
      strain images of the homogeneous and layered phantoms showed some artifacts that
      need to be corrected for, to obtain images of the modulus of elasticity. For in
      vitro and in vivo experiments, the spatial resolution of the technique needs to
      be improved. Furthermore, two-dimensional correlation techniques may be necessary
      in case of nonradial expansion and an off-centre catheter position.

PMID- 9253822
TI  - Electromagnetic hydrophone for pressure determination of shock wave pulses.
AB  - An electromagnetic hydrophone has been designed and tested to determine its
      ability to measure shock wave pulses similar to those produced by lithotripter
      machines. The principle of operation of the hydrophone, its design and
      performance are described. The hydrophone was exposed to 4000 shots and peak
      compressional pressures on the order of 30 MPa without any deleterious effects of
      its performance and operation. The hydrophone can be calibrated directly by
      measurement of the magnetic field of the permanent magnet and voltage induced in
      the electrical conductor. While the spatial resolution of the electromagnetic
      hydrophone is limited by the length of the vibrating conductor and was determined
      to be 5 mm, it can be improved. The overall bandwidth of the hydrophone,
      including its integral preamplifier, had to be limited to 17 MHz; however, the
      hydrophone appears to reproduce correctly the general shape of the propagating
      shock wave pulse. The influence of the hydrophone's bandwidth on the measured
      pulse shape and its amplitude is analysed, and it is shown that it affects rise
      time and peak compressional pressure. However, no deteriorating influence was
      observed in reproduction of peak rarefactional pressure.

PMID- 9253823
TI  - An optical trigger source for hydrophone-based ultrasound measurement systems: a
      feasibility study.
AB  - Ultrasound is routinely used in many medical applications. Concern for the safety
      of subjects undergoing investigations has led to the development of systems to
      quantify the acoustic output of such devices. One system, the NPL ultrasound beam
      calibrator, uses a multi-element hydrophone to determine rapidly the temporal and
      spatial characteristics of the acoustic output. When investigating pulsed systems
      it is necessary to synchronise data acquisition with the launch of the acoustic
      pulse, a procedure that currently can be both time consuming and difficult. This
      article examines the feasibility of using an alternative, optical approach,
      generating a trigger signal in response to the changes in refractive index
      associated with propagation of the acoustic pulse.

PMID- 9253824
TI  - Thresholds for premature contractions in murine hearts exposed to pulsed
      ultrasound.
AB  - A single pulse of high intensity ultrasound can produce either a premature
      ventricular contraction or a reduction in the aortic pressure in frog hearts. The
      objective of this study was to determine whether similar ultrasound exposures can
      produce premature contractions in the mammalian heart. The cardiac activity of
      murine hearts in vivo was monitored noninvasively using electrocardiography and
      plethysmography. Each ultrasound exposure was a single pulse of ultrasound,
      several milliseconds in duration, delivered to the murine heart during diastole.
      The thresholds for producing a premature contraction with a 5-ms ultrasound pulse
      at 1.2 MHz was approximately 2 MPa peak positive pressure. The occurrence of
      premature contractions decreased as the duration of the ultrasound pulse
      decreased. These results found with the mammalian heart are similar to those
      reported earlier for the frog heart. No damage to cardiac tissue was observed
      grossly, although significant hemorrhage occurred to adjacent lung tissue.

PMID- 9253825
TI  - Age dependence of ultrasonically induced lung hemorrhage in mice.
AB  - Thresholds for ultrasonically induced lung hemorrhage were determined in neonatal
      mice (24-36 h old), juvenile mice (14 d old) and adult mice (8-10 weeks old) to
      assess whether or not the threshold for lung hemorrhage is dependent upon age.
      Ultrasonic exposures were at 1.15 MHz with a pulse length of 10 microseconds,
      pulse repetition frequency of 100 Hz and a total exposure duration of 3 min. The
      threshold for lung hemorrhage occurred at a peak positive acoustic pressure of
      approximately 1 MPa for mice in all three age groups. Although the thresholds
      were similar for neonatal, juvenile and adult mice, the sizes of the
      suprathreshold hemorrhages were significantly larger in adult mice than in
      neonatal or juvenile mice.

PMID- 9253826
TI  - Ultrasonically induced lung hemorrhage in young swine.
AB  - Ten-day old swine were used in the final step of a study of the age dependence of
      the threshold for lung hemorrhage resulting from exposure to diagnostically
      relevant levels of pulsed ultrasound. A 2.3-MHz focused transducer (pulse length
      of 10 microseconds, 100-Hz pulse repetition frequency) was incremented vertically
      at several sites for a distance of 2 or 2.5 cm over the chest of the subject for
      a total exposure period of 16 or 20 min. The procedure was repeated at a total of
      four sites per animal. Animals were euthanized and lungs were scored by visual
      inspection for numbers and areas of gross hemorrhages. The threshold level for
      hemorrhage was approximately 1.3-MPa peak positive pressure in water and the
      surface of the animal or, at the surface of the lung, 0.8-MPa peak positive
      pressure, 0.8-MPa fundamental pressure, 0.7-MPa maximum negative pressure and 20
      Wcm-2 pulse average intensity. These values are essentially the same as those
      reported previously for neonatal swine, and neonatal, juvenile and adult mice.

PMID- 9253827
TI  - Acoustic streaming: comparison of low-amplitude linear model with streaming
      velocities measured by 32-MHz Doppler.
AB  - The pressure gradient along the ultrasonic beam results in medium streaming.
      Following Nyborg's analysis of the Navier-Stokes equation, Wu and Du developed an
      approximate solution for the streaming velocity generated by flat and weakly
      focused transducers. We have modified their solution of the Poisson equation by
      directly deriving the Dirichlet boundary conditions to be applied for this type
      of equation. Our numerical results (for the linear case) were about one half
      smaller for flat and weakly focused on Gaussian beam transducers compared to the
      results by Wu and Du. The theoretical calculations were verified using a purpose
      designed 32-MHz pulsed Doppler unit. The applied average acoustic power was
      changed from 1 microW to 6 mW, the burst width was 0.5 microseconds and the pulse
      repetition frequency was 32 kHz. The experiments were done on 4-mm-diameter flat
      and focused (focal distance = 8 and 12 mm) transducers. The streaming was
      measured along the ultrasonic beam from 0-20 mm; at all positions, the maximum
      Doppler frequency was estimated from the recorded spectra. Streaming was induced
      in a solution of water and corn starch. The experimental results showed that, for
      a given acoustic power, the streaming velocity was independent of the starch
      density in water changed from 0.3-40 g of starch in 1 l of distilled water. For
      applied acoustic powers, the streaming velocity changed linearly from 0.2-40
      mm/s. Both the theoretical solutions for plane and focused waves and the
      experimental results were in good agreement.

PMID- 9253828
TI  - Acoustic cavitation nuclei survive the apparent ultrasonic destruction of Albunex
      microspheres.
AB  - The hypothesis tested was that gas bodies capable of nucleating violent
      cavitation activity in vitro would survive the rapid disruption of Albunex
      microspheres by 1-MHz ultrasound. Human erythrocyte hemolysis was used as a proxy
      measure of cavitation. Fluid (5% human serum albumin [HSA]) with or without
      Albunex (ALX) was exposed or sham-exposed to 1-MHz ultrasound (P+ = 1.25 +/- 0.01
      MPa, P- = 0.81 +/- 0.01 MPa; ISPTP approximately 35 W/cm2) for 60 s using 10
      microseconds pulses and a duty factor of 0.5. An equal volume of whole human
      blood was then added to the fluid, followed by a second 60-s treatment.
      Insonation of cell suspensions prepared in previously sham-exposed HSA + ALX
      fluid produced about 4% hemolysis, a level significantly greater than in the
      controls. Insonation of cell suspensions prepared in previously insonated HSA +
      ALX fluid produced about 0.4% hemolysis; this also differed significantly from
      the controls. The data thus support the hypothesis.

PMID- 9253829
TI  - Comparative in vitro activity of doxycycline and oxytetracycline against porcine
      respiratory pathogens.
AB  - Minimum inhibitory concentrations of doxycycline and oxytetracycline were
      determined against 55 Pasteurella multocida strains, 59 Actinobacillus
      pleuropneumoniae strains and 26 Mycoplasma hyopneumoniae strains isolated from
      the respiratory tract of pigs. An additional set of 76 P multocida strains
      isolated from pneumonic pigs was tested for their minimum inhibitory
      concentrations of doxycycline. The P multocida and A pleuropneumoniae strains
      were isolated in France and the minimum inhibitory concentrations were determined
      by an agar dilution method. The M hyopneumoniae strains were isolated in the
      United Kingdom and minimum inhibitory concentrations were determined by a serial
      broth dilution method. All the strains tested were susceptible to doxycycline
      whereas 15 per cent of the P multocida strains and 22 per cent of the A
      pleuropneumoniae strains were resistant to oxytetracycline. Doxycycline
      concentrations inhibiting 90 per cent of strains were 1 microgram/ml for P
      multocida and 2 micrograms/ml for A pleuropneumoniae. The ratio of the minimum
      inhibitory concentrations of doxycycline and oxytetracycline ranged between 1/1
      and 1/4 for the oxytetracycline-susceptible strains and between 1/16 and 1/64 for
      the oxytetracycline-resistant strains. All the M hyopneumoniae strains were
      susceptible to doxycycline and oxytetracycline, the concentrations inhibiting 90
      per cent of strains being 1 microgram/ml and 2 micrograms/ml, respectively. These
      data confirm that doxycycline has a higher in vitro activity against pig
      respiratory pathogens than oxytetracycline.

PMID- 9253830
TI  - Mortality in insured Swedish dogs: rates and causes of death in various breeds.
AB  - Data on over 222,000 Swedish dogs enrolled in life insurance in 1992 and 1993
      were analysed. There were approximately 260 deaths per 10,000 dog-years at risk.
      Breed-specific mortality rates and causes of death are presented for breeds with
      more than 500 dogs at risk that had consistently high or low rates. Breed
      specific mortality ranged from less than 1 per cent to more than 11 per cent.
      True rates and proportional statistics for the cause of death were calculated for
      the entire insured population (250 breeds) and cause-specific mortality rates
      were calculated for the breeds with the highest risk of dying of the most common
      causes. Trauma, tumours and problems related to the locomotor system together
      accounted for more than 40 per cent of all deaths or euthanasias. Although
      limited to insured dogs, these data cover approximately one-third of all Swedish
      dogs and provide baseline mortality data for further population-based studies on
      health and disease.

PMID- 9253831
TI  - Evaluation of plasma chemistry and haematological studies on chickens infected
      with Eimeria tenella and E acervulina.
AB  - Plasma chemistry and haematological studies were conducted on chickens with
      coccidiosis. Male White Leghorn chickens, of two weeks old, were inoculated with
      5 x 10(4) Eimeria tenella sporulated oocysts or with 1 x 10(6) E acervulina
      sporulated oocysts. Blood samples were taken four, seven and 11 days after
      inoculation. A wet chemistry system was applied to measure the plasma activities
      of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,
      gamma glutamyltransferase, creatine kinase, amylase and lactate dehydrogenase and
      the concentrations of creatine, total bilirubin, urate, total cholesterol, total
      protein, albumin, glucose and triglycerides. A dry chemistry system was applied
      to measure sodium, potassium, chloride and calcium. The number of red blood cells
      and packed cell volume were determined by a micro cell counter and blood pH was
      measured with a blood gas analyser. The erythrocyte count, packed cell volume,
      sodium and chloride levels in the chickens infected with E tenella were
      significantly (P < 0.05) lower than those of the uninfected controls. The
      significant decrease in blood pH of the chickens infected with E acervulina
      suggests malabsorption associated with duodenal lesions induced by the infection.

PMID- 9253832
TI  - Surgical treatment of a comminuted articular fracture of the accessory carpal
      bone in a thoroughbred horse.
AB  - The clinical, radiographic and ultrasonographic findings in a case of a
      comminuted articular fracture of the accessory carpal bone of a thoroughbred
      chaser are described, and its surgical treatment and aftercare are detailed. The
      horse made an uneventful recovery and successfully returned to racing.

PMID- 9253833
TI  - Larval Echinococcus multilocularis infection in a dog.

PMID- 9253834
TI  - Ventral peritoneal rectal tear repair in a mare.

PMID- 9253835
TI  - Chronic treatment with naloxone enhances libido in the male goat during
      anoestrus.

PMID- 9253836
TI  - Sporadic milk drop in dairy cows.

PMID- 9253837
TI  - Outbreak of clinical mastitis in dairy cows following 'blitz' therapy.

PMID- 9253839
TI  - "Gut-tie" in steers.

PMID- 9253838
TI  - 'Gut-tie" in steers.

PMID- 9253840
TI  - Abomasal disorders in dairy cattle.

PMID- 9253841
TI  - Equine botulism.

PMID- 9253842
TI  - Management of anthelmintic resistance.

PMID- 9253844
TI  - Virulent foot rot in sheep.

PMID- 9253845
TI  - [Lectures of the annual meeting of the German, Austrian and Swiss Societies for
      Medical and Biological Engineering. Zurich, 4-7 September, 1996].

PMID- 9253843
TI  - Abdominal distension in a cat.

PMID- 9253847
TI  - [38th Congress of the German Society for Pneumology. Freiburg, 5-8 March 1997.
      Abstracts].

PMID- 9253846
TI  - 10th Franco-Belges Meeting of Pharmacochemistry. Luxembourg, 30-31 May 1996.
      Abstracts.

PMID- 9253848
TI  - [XVIII Portuguese Congress of Cardiology. Porto, 20-23 April 1997. Abstracts].

PMID- 9253849
TI  - [Swiss Society of Surgery 84th annual meeting. Davos, 12-14 June 1997.
      Abstracts].

PMID- 9253850
TI  - Is there a nociceptive carousel?

PMID- 9253851
TI  - Targeting ischaemia--cell swelling and drug efficacy.
AB  - Myocardial ischaemia can precipitate fatal arrhythmia, the leading cause of
      mortality in the western world. During ischaemia, cardiac myocytes swell rapidly.
      Such changes in cell volume radically alter the electrophysiology of these cells.
      Ischaemia also alters the potency of antiarrhythmic drugs, with the effectiveness
      of some antiarrhythmics being diminished. Conversely, the ideal antiarrhythmic
      would be 'switched on' by ischaemia. As well as making the drug more potent, this
      would minimize unwanted side-effects by targeting diseased tissue alone. In this
      article, Anthony Wright and Sian Rees discuss possible strategies for developing
      'ischaemia-selective' antiarrhythmics. To date, research has focused on
      potentiation of antiarrhythmic action by membrane depolarization, as occurs
      during ischaemia. The authors suggest that cell swelling alters drug efficacy and
      propose that this could represent a new way of targeting ischaemia.

PMID- 9253852
TI  - Pharmacotherapy of alcohol dependence.
AB  - The current pharmacotherapeutic approaches to alcohol dependence, together with
      the results of a number of clinical trials, are reviewed in this article. Despite
      the somewhat disappointing clinical results, pharmacotherapeutic interventions
      did lead to some small, but significant, improvements in alcohol abstinence
      rates.

PMID- 9253853
TI  - Electrophysiological pharmacology of the autoreceptor-mediated responses of
      dopaminergic cells to antiparkinsonian drugs.
AB  - It is generally accepted that the dopamine receptor ligands currently used in the
      treatment of parkinsonian symptoms mainly stimulate dopamine (DA) receptors of
      the D2 family to produce beneficial effects. Although several animal models can
      provide useful indications on the activity of the antiparkinsonian drugs in the
      brain, the specific cellular sites and the mechanism of action of these
      therapeutic agents are not completely known. In this article, Nicola Mercuri,
      Antonello Bonci and Giorgio Bernardi suggest that the electrophysiological
      effects of antiparkinsonian drugs on nigral dopaminergic cells are related to
      their clinical efficacy. In addition, they report that the stimulation of the D2
      'autoreceptors' located on the residual dopamine-containing cells is implicated
      in the therapeutic response elicited by dopamine receptor agonists in
      parkinsonism. Thus, an electrophysiological approach, which can give basic
      information regarding the actions of direct and indirect DA receptor agonists on
      the dopaminergic neurones, might be relevant for the evolution of the
      pharmacological strategies in Parkinson's disease.

PMID- 9253854
TI  - Adenosine in the mammalian heart: nothing to get excited about.
AB  - Until quite recently, the cardiodepressant actions of adenosine were widely
      accepted. A nucleoside that produces negative chronotropic and ionotropic
      effects, adenosine, has been used clinically as the drug of choice for
      terminating supraventricular (atrioventricular node) tachycardia and is likely to
      play an important part in regulating arrhythmogenic activity as an endogenous
      antiarrhythmic metabolite. Despite this, recent experimental data, particularly
      resulting from in vitro studies using animal models, have shown a paradoxical
      excitable action of adenosine in the heart. In this article, Amir Pelleg and
      Steven Kutalek present the reasons why they continue to believe that any
      excitatory actions of adenosine in the heart are clinically irrelevant.

PMID- 9253855
TI  - Nitric oxide supplementation or synthesis block--which is the better approach to
      treatment of heart disease?
AB  - Nitric oxide (NO) released from endothelium mediates the vasodilatation caused by
      numerous autacoids. Nitric oxide can also be exogenous in that some drugs used in
      cardiovascular disease are NO donors (e.g. glyceryl trinitrate, sodium
      nitroprusside and isosorbide mononitrate used in angina). However, the notion
      that NO is a cardiac protectant, whose mimicry or supplementation is desirable,
      has recently been questioned by data that suggest it is an innocent bystander in
      some conditions, and even a pathological mediator of dysfunction in others. This
      important issue is discussed by Mike Curtis and Ravinder Pabla who suggest it is
      necessary to reappraise the role of NO modulation in cardiac pharmacotherapy.

PMID- 9253856
TI  - Oestrogen/growth factor cross-talk in breast carcinoma: a specific target for
      novel antioestrogens.
AB  - Breast cancer cells express receptors for and are sensitive to a variety of
      steroids, polypeptide hormones and growth factors; the blocking of and/or the
      interference with their biochemical pathways could represent a new approach to
      breast tumour therapy. Antioestrogens achieve such a goal by competing with
      oestradiol for binding to the oestrogen receptors through which intracellular
      effects of the hormone are mediated. Tamoxifen has undergone the most extensive
      clinical evaluations and represents the treatment of choice for the endocrine
      management of breast cancer. Nevertheless, it is well known that tamoxifen
      retains agonist activity both in vitro and in vivo. To circumvent this
      disadvantage, new molecules with steroid-like structure, represented by ICI
      164,384 and ICI 182,780, have been synthesized. In this review, Alessandra de
      Cupis and Roberto Favoni review data about the cross-talk between the two major
      families of breast cancer growth regulator: oestrogens and growth factors,
      focusing on the use of nonsteroidal antioestrogens and the new generation of
      steroidal antioestrogens as possible specifically targeted inhibitors of breast
      tumour proliferation.

PMID- 9253857
TI  - Endothelium-derived hyperpolarizing factor(s): updating the unknown.
AB  - Endothelium-dependent hyperpolarization of vascular smooth muscle is a mechanism
      that contributes to the vasodilator response to shear stress and chemicals acting
      on endothelial receptors. The phenomenon is explained by the release from
      endothelial cells, of an endothelium-derived hyperpolarizing factor(s) (EDHF)
      (s), although its (their) exact nature is still controversial. Indeed,
      endothelial cells produce several substances that are capable of evoking
      hyperpolarization in vascular smooth muscle. However, which of these factors
      represents EDHF under physiological conditions remains unknown. The term EDHF
      should be reserved for a substance(s) that differs from both NO and
      prostaglandins. In this review Jean-Vivien Mombouli and Paul M. Vanhoutte
      consider the possible candidates for EDHF and the arguments that have lead to the
      proposal that these substances fulfil the functions of an endothelium-derived
      relaxing agent. The weaknesses of the available sudies are also discussed. The
      identification of EDHF would allow the understanding of its physiological role
      alongside other known endothelial mediators such as NO and prostacyclin. This
      could lead to the design of new therapies aimed at correcting the impairment of
      EDHF-mediated dilatation in a number of cardiovascular diseases.

PMID- 9253858
TI  - Pharmacological properties of beta 3-adrenoceptors.

PMID- 9253859
TI  - On criteria for functional beta 3-adrenoceptors.

PMID- 9253860
TI  - Tropical diseases and economic change.

PMID- 9253861
TI  - Seroepidemiology of hepatitis A virus antibody in primary school children in Khon
      Kaen Province, northeastern Thailand.
AB  - Hepatitis A is a disease commonly found in Thai children. Since 1984, there have
      been very few reports on the age specific prevalence of hepatitis A virus
      infection in the northeastern part of Thailand, which has the largest population
      and is the poorest area of the country. We studied the seroprevalence of
      hepatitis A virus (HAV) antibody in 3 primary school children in different areas
      of Khon Kaen Province, northeastern Thailand. Anti-HAV level was assayed by
      ELISA. Four hundred and forty-one children age 6-12 years were selected from one
      primary school in the urban area and two from rural areas. The highest prevalence
      was 22.6% at age 12 years and 0 at age 6 years. The seroprevalence was highest,
      45%, in rural school children of the lowest socioeconomic status as compared to
      10.8% and 2.6% in other urban school children. The overall prevalence was 12.7%
      and the age specific prevalence with 95% CI are presented. These data indicated a
      much lower seroepidemiological prevalence than previously reported and might be
      related to the level of socioeconomic and standard of public sanitation and
      living conditions.

PMID- 9253862
TI  - High hepatitis C seroprevalence in Thai intravenous drug abusers and qualitative
      risk analysis.
AB  - One of the high risk groups of hepatitis C virus infection is intravenous drug
      abusers (IVDAs). The study of HCV seroprevalence and some qualitative risk
      factors in this target group can be valuable for prevention of the infection.
      During June to October 1992, a cross-sectional study of 150 intravenous male drug
      abusers seeking medical treatment at Phranangkhlao and Rajavithi Hospitals was
      conducted. Blood specimens were collected for determining anti-HCV antibody by
      EIA. An in-depth interview was carried out searching for some qualitative risk
      factors in anti-HCV positive and negative IVDAs. It was found that 95.33% of
      studied IVDAs were positive for anti-HCV antibody. There was no significant
      difference between the prevalence of anti-HCV and their ages (p > 0.05). The
      antibody prevalence trended to be higher with the longer duration of drug use.
      The positive rate of IVDAs who had injected more than 8 years was significantly
      higher than that of IVDAs who had injected less than 2 years (100% and 85.71), p
      = 0.004. Alanine amino-transferase (ALT) levels and anti-HIV antibodies were
      determined. IVDAs with higher levels of anti-HCV had higher percentages of ALT
      abnormality and anti-HIV positive rates. Data from in-depth interview showed that
      the longer duration of imprisonment, tattoo/ear piercing, extramarital relations
      without using condoms, the longer duration of drug use and needle/syringe sharing
      were potential risk factors for HCV infection in this target group.

PMID- 9253863
TI  - Protective antibody after a 'one dollar' hepatitis B vaccine.
AB  - The seropositivity rate of anti-HBs after hepatitis B vaccines, "Hepavax B", a
      one-dollar per dose vaccine produced by Korean Green Cross Corporation, Korea
      which were widely distributed and used for the first few years in the National
      Expanded Program on Immunization in Thailand were assessed in children who
      regularly came for immunization at the Well Baby Clinic at the Children's
      Hospital between June to December 1994. The schedule for hepatitis B immunization
      is at birth, 2 and 6 months of age. The seropositivity rate of anti-HBs at 6
      months after the last dose were 86.3% and 87.7% at 12 months which was comparable
      to the seropositivity rate after other more expensive hepatitis B vaccines at 2
      years (88.1%). This result should convince people that a one-dollar hepatitis B
      vaccine, "Hepavax" is immunogenic and expected to be as effective as other
      expensive hepatitis B vaccines. The marked reduce in the cost of hepatitis B
      vaccines will enable us to prevent and ultimately control of worldwide hepatitis
      B infections in the future.

PMID- 9253864
TI  - In vivo and in vitro studies on the morphological change in the monkey epidermal
      Langerhans cells following exposure to dengue 2 (16681) virus.
AB  - A direct comparison of skin Langerhans cell (LC) morphologic change following in
      vivo and in vitro exposure to dengue-2 (DEN-2) virus (16681) was performed in the
      monkey to investigate any differences in functional activity profiles. Time-lapse
      study of skin biopsy at the intradermal (id) virus injection sites, and thin skin
      sheets removed from the monkey with exposure to virus in culture medium, revealed
      a highly active migration of epidermal LCs in both sets of experimental
      specimens. The migration led to a relatively higher number of dendritic cells
      (DC) which appeared in active migrational profiles, in the superficial dermis.
      Moreover, obvious cytoplasmic structural changes, corresponding to their
      immunologic function, were observed in these superficial dermal DCs 2 hours after
      exposure. Despite their similar changes, early and late endosomes with degraded
      virus-like particles could be seen in the skin sheets owing to lagging in
      cellular physiological process in vitro, but none in the skin biopsies. Existence
      of these endosomes, which was extremely difficult to visualize in vivo,
      highlighted the mode of antigen processing by the endocytic pathway. The present
      study showed that the epidermal LC was a potent antigen-presenting cell for
      eliciting the success of id immunization and carried out the immunological
      activity in vivo or in vitro in the like manner, in respect to the physiological
      conditions.

PMID- 9253865
TI  - An appraisal of some recent diagnostic assays for Japanese encephalitis.
AB  - A study was undertaken in South Arcot district of Tamil Nadu, India to assess
      relative merits of selected diagnostic techniques for Japanese encephalitis.
      During the transmission seasons of 1993-1995, a total of 85 patients (mostly
      pediatric) clinically diagnosed as acute encephalitis or other related central
      nervous system (CNS) disorders were examined; in 53 (62.4%) a laboratory
      diagnosis of JE was established. In terms of diagnostic value, immunoglobulin M
      (IgM) antibody capture ELISA (MAC ELISA) on convalescent serum had the highest
      sensitivity (89%) and negative predictive value (NPV) (50%). This was followed by
      MAC ELISA on acute serum and CSF which had similar sensitivity (84%) and NPV
      (40%). The hemagglutination inhibition test and Toxorhynchites splendens
      inoculation technique for virus isolation were also similar in sensitivity (68%)
      and NPV (25%). The virus antigen detection technique by IFA in cells of
      cerebrospinal fluid (CSF) was the least sensitive (58%). The distinct advantage
      of the acute serum ELISA is that it can be carried out on a single finger-prick
      blood specimen. The IFA on CSF cells is the most rapid diagnostic test since it
      requires only 2-3 hours to complete. Therefore, both these tests also offer
      potential tools for JE surveillance programs.

PMID- 9253866
TI  - Monoclonal antibodies against respiratory syncytial virus for rapid detection and
      subgroup determination.
AB  - Thirty-one hybridomas producing monoclonal antibodies (MAbs) against structural
      proteins of RSV subgroup A (Long strain) and RSV subgroup B (Japanese wild
      strain) were produced and separated into three groups by their reactivities with
      RSV-A and RSV-B using IFA. Group I was specific to RSV-A, Group II was specific
      to RSV-B and group III was specific to both subgroups. Characterization of
      selected two MAbs from each group indicated that three MAbs recognized
      phosphoprotein (P) and the others recognized fusion protein (F). All of the
      selected MAbs were IgG1 and carried kappa light chain. These selected MAbs can be
      used to detect the presence of RSV from NPAs and classify them into two
      subgroups. The infection rates of RSV in Thai children are very low and most of
      them were RSV subgroup A.

PMID- 9253867
TI  - Clinical and laboratory profile of sixty patients with AIDS: a South Indian
      study.
AB  - Sixty patients who fulfilled the WHO case definition of acquired immunodeficiency
      syndrome (AIDS) were admitted and treated between January 1993 and June 1995 in
      JIPMER Hospital, Pondicherry, South India. Their mean age was 30.3 +/- 6.4 years.
      Male: female ratio was 5 : 1. The heterosexual route was the major mode of
      transmission (96.7%). Fever was the commonest presentation (98.3%), followed by
      weight loss (85%) and cough (36.7%). The commonest opportunistic infection seen
      was tuberculosis (pulmonary, extrapulmonary - single or in combination) followed
      by esophageal candidiasis. Cryptococcal meningitis, intestinal crytosporidiosis,
      CNS toxoplasmosis, Pneumocystis pneumonia and group B Salmonella septicemia were
      the other infections encountered. Ten out of the 38 patients with tuberculosis
      were followed up on antituberculous treatment for 6 months. Seven out of 18
      patients with esophageal candidiasis were treated with ketoconazole.

PMID- 9253868
TI  - Impact of school-based HIV and AIDS education for adolescents in Bombay, India.
AB  - The HIV/AIDS epidemic in India is expanding rapidly. The present study is a pre
      test-post-test evaluation of a school-based HIV/AIDS educational program. The pre
      test was administered to 2,919 students regarding modes of transmission and
      prevention of HIV/AIDS. An education program was instituted for one half school
      day at ten secondary schools. Principals of two schools refused to participate.
      One month later, the post-test was administered to 2,400 students. Before the
      educational intervention only 50% of the students knew that HIV/AIDS is
      transmitted sexually, only 34% knew that there are no medicines that cure
      HIV/AIDS and 24% thought that HIV is transmitted by mosquito bites. After the
      intervention, 95% of the students knew that HIV/AIDS is transmitted sexually, 92%
      knew that there is no HIV/AIDS cure and 76% knew that HIV/AIDS is not transmitted
      by mosquitos. There was a substantial increase in correct knowledge about
      HIV/AIDS among students after our single educational program. This suggests that
      school-based educational programs for adolescents in India can succeed in
      providing basic information regarding HIV/AIDS.

PMID- 9253869
TI  - Knowledge, attitude, and preventive practice survey regarding AIDS comparing
      registered to freelance commercial sex workers in Iloilo City, Philippines.
AB  - A survey of female commercial sex workers (CSW) in Iloilo City, Philipines, was
      conducted in October and November 1995 to determine the level of knowledge,
      attitudes, and preventive practices regarding HIV/AIDS to guide future education
      programs. CSWs in the Philippines were categorized as registered or freelance.
      Registered CSWs included "hospitality girls" from licensed bars, night clubs, and
      massage parlors who have registered with the local social hygiene clinic (SHC).
      Freelance CSWs are not registered. 110 registered and 46 freelance CSWs were
      surveyed. We compared demographic data, scores from a basic knowledge test, and
      preventive practices between registered and freelance CSWs. Demographic data
      indicate that registered CSWs often originate from provinces outside of the
      Visayan Islands (25%) and most have never been married (93%). Freelance CSWs
      included more married (11%) and separated (11%) women from nearby cities.
      Knowledge test scores of registered and freelance CSWs were not significantly
      different. 90-96% of CSWs correctly answered questions regarding modes of
      transmission. However, 25% still believed it is possible to contract AIDS from
      using a public restroom. Registered and freelance CSWs believed their risks for
      AIDS to be equally great. However, 38% of freelance CSWs admit to never or almost
      never using condoms compared to 15% of registered CSWs. Licensed establishments
      and a support staff at the social hygiene clinic may provide a relatively
      structured working environment, giving registered CSWs security and confidence to
      insist on condom use. In most cases, condom use seems to depend on male customer
      compliance, and CSWs, especially freelancers, cannot afford to insist on condom
      use. The CSWs indicated that they learned most about AIDS through health
      personnel and television.

PMID- 9253870
TI  - Epidemiology of blood-borne viruses: a study of healthy blood donors in Southern
      Pakistan.
AB  - There are only a few published reports regarding the prevalence of hepatitis B
      virus, hepatitis C virus and human immunodeficiency virus in Pakistani blood
      donors. The true extent of the prevalence of these viral infections in healthy
      adults in unclear. We examined blood donors attending the Aga Khan University
      Hospital and blood donation camps in the cities of Karachi and Hyderabad,
      Pakistan for the presence of hepatitis B surface antigen (HBsAg), antibodies to
      hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV).
      Relationship of anti HCV to the surrogate marker alanine aminotransferase (ALT)
      was also examined. Prevalence of HBsAg was found to be 2.28% (1,173/51,257), anti
      HCV was 1.18%(198/16,705) and that of anti HIV to be 0.02% (10/51,257). Higher
      rate of prevalence of HBsAg and anti HCV was observed in the younger age group of
      21 to 30 years. Male to female ratio for HBsAg was 2.5:1 and for anti HCV 1:1.
      Seropositivity for HBsAg was significantly greater than anti HCV (p < 0.0001). No
      clear relationship was found between high ALT (>55 U/l) and anti HCV positivity.
      Further examination of seropositive samples for HIV revealed only one donor to be
      positive by Western blot also. Prevalence of hepatitis B and C in the adult blood
      donor population in Southern Pakistan is higher than western countries but is
      similar to regional countries. This study also suggested that high ALT is not a
      useful surrogate marker for hepatitis C virus. Prevalence of HIV in this donor
      population is very low and is comparable to the western countries.

PMID- 9253872
TI  - Comparison of separated-lymphocyte and whole-blood lymphocyte proliferation
      assays for evaluating rabies-induced cellular immunity.
AB  - A whole-blood lymphocyte proliferation assay was compared to a standard method
      requiring the isolation of peripheral blood mononuclear cells (PBMC). Both
      methods were used to measure the cell-mediated immune responses to rabies in
      rabies-vaccine recipients. Whole-blood cells gave moderately higher
      lymphoproliferative responses in terms of stimulation indices than did separated
      PBMC. The results obtained from these two methods can be considered equivalent
      for the purpose of quantitating cellular reactivity to rabies. The use of whole
      blood has advantages over the standard isolated-PBMC method.

PMID- 9253871
TI  - Study of young women vaccinated against rubella virus for 10 years in Taiwan.
AB  - Since the licensing of the rubella virus vaccine (RA 27/3 strain) in 1979,
      clinical studies on the RA 27/3 strain vaccine, which gives rise to high titer
      antibody, have been reported. In the present study, this vaccine was used to
      examine the immune response in young women. Volunteers without the previous
      immunity to rubella virus screened by hemagglutination inhibition (HAI), latex
      agglutination (LA), fluorescence immunoassay (FIA) and solid-phase immunoassay
      (SPIA) tests were injected with Rudivax vaccine or Meruvax II vaccine. Adverse
      reactions occurred between 10 and 20 days after vaccination in 30% of the
      volunteers. After 28-35 days, vaccinees developed antibodies against rubella
      virus. The titer of rubella antibody reached it's peak from the 40th day through
      the 100th day. One year after vaccination, the geometric mean titer (GMT) of
      rubella virus antibody still remained over 1 : 64 (HAI) and 1 : 38.2 (FIA), and
      SPIA IgG RI mean was 2.80. Two years later, the antibody titers were 1 : 52 by
      HAI and 1 : 32.1 by FIA, and SPIA IgG RI mean was 2.75. After 5 years, the
      antibody titers were 1 : 48.6 (HAI) and 1 : 28.2 (FIA), and SPIA IgG RI mean was
      2.74. After 10 years, the anti-rubella virus antibody titers were 1 : 38.9 (HAI)
      and 1 : 25.1 (FIA), and SPIA IgG RI mean was 2.42. LA antibody still remained
      seropositive. In conclusion, the rubella vaccine RA 27/3 is safe and efficient,
      and it is applicable for the control of the rubella in Taiwan.

PMID- 9253873
TI  - Amphotericin B with or without flucytosine followed by fluconazole as primary
      therapy for cryptococcal meningitis in patients with AIDS.
AB  - Eighteen consecutive AIDS patients with a first episode of cryptococcal
      meningitis were enrolled in the study to evaluate the efficacy and tolerability
      of amphotericin B with or without flucytosine followed by fluconazole as primary
      therapy for cryptococcal meningitis in patients with AIDS. The treatment
      consisted of intravenous amphotericin B 0.6 mg/kg daily with or without
      flucytosine (150 mg/kg d in four divided doses) for 2 weeks which was then
      followed by oral fluconazole 400 mg daily for 8 weeks. After completion of
      primary therapy, all patients received a maintenance dose of oral fluconazole 200
      mg daily. The primary therapy was successful in 17 (94%) of the 18 patients. The
      median length of time to the first negative cerebrospinal fluid culture for
      Cryptococcus neoformans in the 17 patients with successful treatment was 3 (range
      2 to 6) weeks. No patient had to discontinue the treatment due to adverse drug
      reactions. During a mean observation period of 26.94 weeks, no relapse case was
      documented among the 17 patients. Our results indicate that this regimen as
      primary therapy for cryptococcal meningitis in AIDS patients is effective and
      well tolerated.

PMID- 9253874
TI  - Bacterial diarrhea in Laos, a region where cholera was endemic.
AB  - There were cholera outbreaks in Lao PDR since 1993. Two provinces were epidemic
      areas of cholera in 1993. However the area of cholera occurrence increased to 7
      provinces through 1994. Then a bacterial survey had done for the purpose of
      public health improvement. EPEC was markedly isolated from the hospital in
      Vientiane. In apparent infection of Salmonella and non-01 Vibrio cholerae with
      soldiers stationed in the island in Mekong River belong to Vientiane were pointed
      out. The outbreak of diarrhea in suburban village of Vientiane, the diarrhea was
      not due to cholera but due to Shigella dysenteriae and Aeromonas sobria. As far
      as results in the capital city Vientiane and the Vientiane province go, it could
      say that there was no record and isolation of V. cholerae or non-01 V. cholerae
      0139 in this study. On the contrary, Vibrio cholerae 01 serotype Eltor Ogawa was
      isolated although the community declared the end of the cholera outbreak. This
      study pointed out the importance of establishing sanitary conditions and health
      education systems in Lao PDR.

PMID- 9253875
TI  - Anti-PGL-1 antibody levels in Thai leprosy patients.
AB  - Phenolic glycolipid - 1 (PGL-1) is a Mycobacterium leprae specific cell wall
      component. It is an immunodominant antigen and can induce a strong humoral immune
      response. IgM antibody levels against PGL-1 were measured in Thai leprosy
      patients between October 1992-April 1994 by a commercially available M. leprae
      particle agglutination test (MLPA). The percentage of seropositivity was much
      higher in newly untreated multibacillary (MB) patients (83.9%) than in
      paucibacillary (PB) patients (17.8%). Antibody levels in the MB group varied in
      the range 32-8,192, whereas they varied in the range 32-256 in the PB group.
      Patients being treated with multidrug therapy (MDT) were 68.3% and 19.4%
      seropositive in the MB and PB groups, respectively. Seropositivities in control
      serum specimens were 11.3% in active pulmonary tuberculosis patients, 2.6% in
      dermatologic patients and 4.4% in a healthy population. In conclusion, the anti
      PGL-1 assay using MLPA appears to be a sensitive and specific diagnostic tool for
      the diagnosis of MB patients. Additionally, it may provide an alternative to the
      BI determination in monitoring MB patients under MDT, and also in the
      surveillance of such patients after MDT.

PMID- 9253876
TI  - In vitro activity of cefoperazone-sulbactam: Singapore experience.
AB  - In vitro activity of commonly used antimicrobial agents against consecutively
      isolated 521 strains of Gram negative bacilli causing serious infections in the
      National University Hospital, Singapore were tested in parallel with cefoperazone
      sulbactam combination. With the combination complete resistance of 2% and
      intermediate resistance of 5% were noted among the 521 strains tested. Resistance
      to imipenem was low (5%) but resistance against other antimicrobial agents varied
      from 12% (amikacin) to 80% (ampicillin). In vitro data demonstrated a possible
      future role for cefoperazone-sulbactam in the treatment of sepsis caused by Gram
      negative bacilli in our hospital.

PMID- 9253877
TI  - Utility of catalytic models in the estimation of incidence and prevalence of
      malaria in a hyperendemic situation.
AB  - Simple catalytic models were used for estimating the true incidence of malaria in
      hyperendemic villages of Koraput District in Orissa State where Plasmodium
      falciparum is predominant. The hill top villages recorded a slide positive rate
      of 45.68. The daily rate of inoculation among infants was estimated to be
      0.00781. The inoculation rate was so high that the recovery from one infection
      was compensated by the subsequent infection and hence the prevalence continued to
      increase with age. The model adequately represents the observed data for infants
      but could not be used for estimating the true prevalence in the adult population
      without incorporating other factors like immunity and superinfection.

PMID- 9253878
TI  - Anthelminthic treatment raises plasma iron levels but does not decrease the acute
      phase response in Jakarta school children.
AB  - The study was conducted to investigate the impact of intestinal helminthiasis and
      treatment on iron status and acute phase response (APR) among urban Indonesian
      primary school children, aged 8-11 years old. The prevalence of helminthiasis
      among these children was; Ascaris lumbricoides, 81.6%; Trichuris trichiura,
      88.3%; and mixed infection of A. lumbricoides and T. trichiura, 70.0%. Of 120
      children enrolled in the investigation, 59 received a single 400 mg dose of
      albendazole, and 61 received a placebo. Ten days following treatment, the
      prevalence of ascariasis and trichuriasis in the treatment group diminished to 0%
      and 27%, respectively, and in the placebo group to 63.9% and 68.9%. Plasma iron,
      hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white
      blood cell (WBC), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis
      factor (TNF) concentrations were determined prior to the intervention and 10 days
      after. Plasma iron concentrations and WBC count rose in the treatment group (p=<
      or =0.05) when compared to baseline status. Increases in hemoglobin
      concentrations observed in the treatment group 10 days post-treatment were not
      statistically significant. CRP, IL-1, IL-6 and TNF were found to be within normal
      limits for both groups both before and after treatment. ESR increased
      significantly in both treatment and placebo groups when compared the rates
      measured before treatment. These findings show that treatment with albendazole is
      associated not only with a decreased worm burden in school children, but also a
      rise in plasma iron.

PMID- 9253879
TI  - Soil-transmitted helminthiases in China: a spatial statistical analysis.
AB  - The prevalence of the soil-transmitted helminthiases is extremely high in some
      rural areas in China. The endemic foci of these human parasites constitute one of
      the most neglected public health problems. A large scale survey on human
      parasites (1988-1992) was conducted in China. The prevalences of the soil
      transmitted helminthiases in the 30 provinces, autonomous regions and
      municipalities were reported and correlated with ecological factors (Yu et al,
      1994; Xu et al, 1995). In this paper, we re-examined and analyzed the reported
      results with a spatial pattern test statistic, the D statistic. The values of the
      D statistic indicated that the spatial correlation of the prevalence of the soil
      transmitted helminthiases in China was significant. We also found that the
      spatial correlation of the prevalence could largely be explained by the paddy
      field area per capita. The correlation of the prevalence of the soil-transmitted
      helminthiases and the paddy field area per capita was higher than the correlation
      of the prevalence with the factors found previously by Xu et al (1995).

PMID- 9253881
TI  - Comparative trials using albendazole and mebendazole in the treatment of soil
      transmitted helminths in schoolchildren on Penang, Malaysia.
AB  - Trials using albendazole and mebendazole, as single 400 mg dose treatments,
      against soil-transmitted helminths, were carried out in 7-9 and 10-12 years-old
      schoolchildren living in urban and rural environments in Penang, Malaysia. Both
      drugs were equally effective in treating trichuriasis and ascariasis in both age
      groups and environments. However, mebendazole is not so effective in the
      treatment for hookworms when compared to albendazole. It is suggested that
      albendazole should be considered the drug of choice for mass chemotherapy for
      Penang.

PMID- 9253880
TI  - Monoclonal antibody-based ELISA for the detection of circulating Entamoeba
      histolytica antigen in hepatic amebiasis in hamsters (Mesocricetus auratus).
AB  - Circulating amebic antigens were determined by using a sandwich ELISA with
      specific monoclonal antibody in the sera of 35 group I hamsters, 7 of which were
      sacrificed at intervals after hepatic inoculation with 500,000 axenically grown
      HM:1:IMSS strain of E. histolytica trophozoites, 7 group II infected hamsters in
      which metronidazole treatment was given and 18 group III uninfected controls.
      Amebic antigenemia was demonstrated in 5 of 7 (71.4%), 6 of 7 (85.7%), 7 of 7
      (100%), 7 of 7 (100%) and 7 of 7 (100%) of group I hamsters on days 5, 10, 15, 20
      and 30 of infections respectively, whereas 6 of 7 (85.7%) of group II hamsters
      were weakly positive, one was negative and all 18 group III hamsters were
      negative. The sensitivity of the assay was 100% after the animals were infected
      15 days onwards. The level of antigenemia in hamsters of group I with abscess was
      significantly higher than those of the same group without abscess (p < 0.05).
      Absence or reduction of antigenemia after treatment could be interpreted to mean
      a positive test of cure and favorable therapeutic response. The MAb-PAb-based
      ELISA for the detection of circulating E. histolytica represents a simple and
      sensitive diagnostic test for invasive amebiasis in hamsters. Application of this
      test in amebic liver abscess patients should be of diagnostic value for
      indication of present infection or test of cure after successful treatment.

PMID- 9253882
TI  - Profile of heroin addicts in Nagaland, India.
AB  - A total of 395 drug addicts from Nagaland, India during 1992-1993 were studied.
      Of these, 331 (83.8%) were primary abusers of heroin. Mean age of the group was
      21.8 years +/- SD 3.84. Of these 5.2% were females. The majority were unmarried
      (92.1%) and 52% had completed 10 years of schooling. Drug-related school dropout
      rate was 72.8%. Unemployment was predominant (90.3%) in the group, of which most
      were never employed. Christianity was the main religion (90.9%) of the group. The
      mean age at first use of heroin was 17.6 years +/- SD 3.68. The mean duration of
      dependence on heroin was 4.4 years +/- SD 2.8. Heroin was injected by 80.9%
      subjects. Friends were the main source of introduction. Concurrent use of
      tranquilizers and codeine containing cough syrups was prevalent in the event of a
      short supply of heroin. The involvement of young, unemployed, unmarried persons
      in heroin addiction; widespread prevalence of the injection route and needle
      sharing; chronicity of heroin dependence; paucity of specialized treatment
      avenues and proximity to the Golden Triangle facilitating illicit traffic, have
      contributed to emergence of heroin addiction as a major public health problem in
      Nagaland.

PMID- 9253883
TI  - Sequential pattern of non-medical drug use in the drug career of opiate
      dependents in Nagpur, India.
AB  - A study was carried out in a group of opiate addicts who reported to various
      centers in Nagpur city, India, to know the sequential pattern of nonmedical drug
      use in the drug career of opiate dependents in Nagpur. The mean age of the study
      group was 28.2 years, the majority were males, educated up to 10th standard,
      employed in various occupations like petty business, vehicle driving, etc, with
      an average monthly income of Rs. 316. The average number of drugs ever used per
      person was 3.7 +/- 1.2, those recently used was 2.6 +/- 0.9 and currently used
      was 2.2 +/- 0.6. The study group experienced 13 drug types in their addict
      careers. Beedi?cigarette was the first drug abused by the majority. Drug careers
      starting with beedi?cigarette, progressing to alcohol and then to canabis and
      finally to heroin were observed in a majority of subjects. There appeared to be a
      shift from multidrug use to the singular combination of heroin and
      beedi?cigarette currently. Use of all other drugs declined in favor of heroin as
      the career progressed. The study indicates that preventive programs should be
      directed at reducing the use of initial drugs like beedi?cigarette and alcohol
      and also reducing the social acceptability of these drugs as measure for
      preventing progression to hard drugs like heroin.

PMID- 9253884
TI  - Obesity in primary care patients in Kelantan, Malaysia: prevalence, and patients'
      knowledge and attitudes.
AB  - This study measured the body mass index (BMI), and assessed attitudes and
      knowledge about obesity, of 197 male and 217 female patients aged 20-59 years
      attending the primary care clinic of the university hospital in Kelantan,
      Malaysia. There was no significant difference between the mean BMI of males
      (23.7) and females (24.2). In the overweight group (BMI 25-29.9) were 60 men
      (30%) and 66 women (30%). In the obese group (BMI 30 and above) were 12 men (6%)
      and 22 women (10%). Both diabetes mellitus and hypertension were associated with
      significantly higher BMI's. Knowledge about obesity was lacking. Sixty-three
      (15%) failed to recognize that obesity is bad for health. When asked the causes
      of obesity, 88 (21%) failed to mention either diet or lack of exercise. "Being
      happy" was suggested as a cause by 32 (8%). When asked if certain foods would
      cause obesity if eaten in excess, 45 (11%) said "No" for fatty foods, and 164
      (40%) said "No" for sweet foods. Concerning appearance, 30 (15%) men regarded an
      obese man as normal or even handsome, while 49 (23%) women regarded an obese
      woman as normal or beautiful. Obesity is common among our adult patients, and is
      associated with some of their common health problems. However, a substantial
      minority do not regard obesity as unhealthy, do not relate it to diet or lack of
      exercise, do not recognize important groups of fattening foods, and do not regard
      obesity as unattractive.

PMID- 9253885
TI  - Incidence and risk factors for carbohydrate intolerance in Thai infants with
      acute diarrhea: an outpatient-based study.
AB  - Until recently, information concerning carbohydrate intolerance complicating
      acute infantile diarrhea of outpatients in Thailand has been lacking. This
      prospective study was undertaken to determine the incidence and risk factors of
      secondary carbohydrate intolerance in outpatients. Of 197 well-nourished infants
      with acute diarrhea who were seen at the outpatient department of Songklanagarind
      Hospital between July 1991 and June 1992, 62 infants (31.3%) had carbohydrate
      intolerance, and 7 of the 62 (3.5%) also had acquired monosaccharide intolerance.
      The clinical characteristics that predicted infants with carbohydrate intolerance
      were : a low bodyweight relative to the length, dehydration (OR 4.55, 95% CI
      1.1.5-17.9), the presence of mucus in diarrheal stools (OR 2.79, 95% CI 1.23
      6.32) and rotavirus infection (OR 3.49, 95% CI 1.20-10.18).

PMID- 9253886
TI  - Vitamin A status of Filipino preschool children given a massive oral dose.
AB  - The protection period of a 200,000 IU of vitamin A on Filipino children was
      determined. Subjects were 105 children aged 1-5 years given a single massive dose
      during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was
      measured by HPLC at baseline, one, two, four and six months after the
      administration of the dose. Results showed that baseline serum retinol levels
      were significantly lower than all follow-up values. Serum retinol values were
      maintained at levels higher than pre-supplementation values although the values
      decreased on the second month after supplementation. The proportions of deficient
      and low (< 20 microg/dl) levels were significantly lower one and six months after
      supplementation. All follow-up serum retinol levels of children with deficient
      and low values at baseline were significantly lower (p < 0.001) than those with
      normal values. The WHO recommendation of 200,000 IU was effective in increasing
      serum retinol concentrations and maintaining it above pre-supplementation levels
      up to 6 months after administration of the dose. It also replenished organic
      vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of
      infection also decreased among the children. Supplementation with vitamin A has
      likewise resulted in an increase in hemoglobin values and a decrease in the
      proportion of anemics (Hb < 11.0 g/dl) among the children.

PMID- 9253887
TI  - Effect of air pollution on respiratory symptoms of junior high school students in
      Indonesia.
AB  - In 1994, 16,187 junior high school students were surveyed in Jakarta and
      surrounding cities, Indonesia, to study the effect of air pollution on
      respiratory illnesses. Nitrogen dioxide (NO2) was measured by the filter badge
      developed by Yanagisawa and Nishimura as a measure of air pollution. The average
      concentration of NO2 is the highest in central Jakarta and Tangerang (22-30 ppb),
      the lowest in rural areas (5-11 ppb), and in other cities, 11-20 ppb. Self
      administered questionnaires were given to the students in 29 schools to obtain
      respiratory symptoms of cough, phlegm and wheeze. A significant relationship was
      found in this study between NO2 exposure levels and prevalence rates of cough,
      phlegm, and wheezing without cold, which were 27.7 to 38.7%, 15.0 to 21.9%, and
      1.4 to 2.9%, respectively. Prevalence rates of persistent cough and persistent
      phlegm were 7.3 to 10.8% and 4.5 to 5.0% respectively. These rates were higher
      than those found by other researchers. This difference may be partly due to the
      survey methods. The more polluted, the higher the prevalence rate of respiratory
      symptoms.

PMID- 9253888
TI  - Strokes in Thai children : etiology and outcome.
AB  - In Asian countries, specific etiology and outcome of stroke in children are
      rarely reported. During January 1979 to December 1997, 68 children with stroke,
      admitted to the Department of Pediatrics, Ramathibodi Hospital, Bangkok were
      reviewed for etiology and outcome; 38 patients (22 males) had ischemic stroke and
      30 (20 males) had hemorrhagic stroke. Severe headache, vomiting, disturbance of
      consciousness and papilledema were prominent presentations of hemorrhagic stroke.
      Bleeding from vascular anomalies of the brain (AVM) was the most common etiology
      of hemorrhagic stroke while septic and non-septic emboli from congenital and
      acquired heart diseases were the most common cause of ischemic stroke. The
      mortality rate was 7% and 9% in hemorrhagic and ischemic strokes, respectively.
      Complete recovery was observed in 52% of cases of hemorrhagic stroke but in only
      26% of ischemic stroke. Hemiparesis was the most common residual neurological
      deficit with higher occurrence in ischemic stroke.

PMID- 9253889
TI  - An outbreak of horseshoe crab poisoning in Chon Buri, Thailand: clinical,
      toxicologic and therapeutic considerations.
AB  - In 1994-1996, an outbreak of horseshoe crab poisoning by eating toxic eggs of the
      horseshoe crab Carcinoscorpius rotundicauda affected over 100 persons in Chon
      Buri which located on the eastern coast of Thailand. We discuss clinical
      description and management of this first major outbreak. The responsible toxin
      has been partially purified by means of ultrafiltration and high performance
      liquid chromatography. The horseshoe crab toxin is identified as tetrodotoxin
      (TTX) and anhydro TTX.

PMID- 9253890
TI  - Progress in studies on the overwintering of the mosquito Culex tritaeniorhynchus.
AB  - A detailed review is presented of half a century's research in Japan, Korea and
      the temperate zone of China on the overwintering of Culex tritaeniorhynchus, the
      main vector of Japanese encephalitis. The evidence indicates that in the
      temperate zone, two types of overwintering strategy can be distinguished in Cx.
      tritaeniorhynchus, ie survival by adults in situ in a dormant state, or migration
      by individuals which are in reproductive diapause. The authors contend that the
      former strategy is not very effective, and individuals which overwinter in this
      way do not constitute the main source of the next season's mosquito populations.
      On the contrary, new mosquito populations seem to be established by groups of
      adults which appear suddenly, early in the year, and which are probably windborne
      migrants from the south. It is concluded that further research into the mode of
      overwintering of Cx. tritaeniorhynchus should focus on the effective source of
      the populations which appear in temperate areas in early spring, and that efforts
      should be made to increase our understanding of the migration patterns of this
      species.

PMID- 9253891
TI  - Genetic differentiation among three populations of Anopheles minimus of Guangxi
      and Yunnan Provinces in the People's Republic of China.
AB  - Electrophoretic studies were carried out on isozymes of 3 populations of
      Anopheles minimus collected from Guangxi and Yunnan Provinces of the People's
      Republic of China in 1993. Eight proteins were analyzed by 5% polyacrylamide gel
      electrophoresis. The most variable population, Y-F, was highly polymorphic at 14
      of 20 loci (P=0.700) with an average heterozygosity H of 0.340. P values of 0.500
      and 0.700, and H values of 0.220 and 0.210 were obtained for each from 'Guangxi
      Lab' (GX-L) and 'Yunnan-Lab' (Y-L), respectively. Nei's genetic distances (D)
      between Y-L and GX-L, Y-F and GX-L, and Y-F and Y-L were 0.1131, 0.1946 and
      0.1069, respectively. These results suggest that GX-L is distant from the 2 other
      populations, Y-L and Y-F, and that this genetic differentiation between the 2
      populations of Yunnan and Guangxi Provinces corresponds to the forms A and B,
      which were morphologically classified by Xu et al (unpublished).

PMID- 9253892
TI  - Laboratory evaluation on the toxic effects of bednets impregnated with permethrin
      against malaria mosquitos.
AB  - In the laboratory, bednets impregnated with 250mg ai/m2 and 500mg ai/m2
      permethrin caused respectively the mean mortalities of 86.6% within 13 months and
      87.2% within 17 months on laboratory-bred An. sinensis, while they caused average
      mortalities of 58.3% within 4 months and 73.8% within 10 months on An. dirus
      respectively. The bioassay results of KT50 and LT50 on the two species showed
      that KT50 is shorter than LT50 after exposure to the treated bednets. The ratio
      is 1:2.16 - 1:3.05. It was observed Anopheles had obviously secondary knocked
      down after exposure to the treated bednets and there is obvious resurgent after
      Anopheles have been knocked down. When the temperature goes up the resurgence
      gets shorter, the resurgence rate gets higher and the mortality gets lower. It
      showed that permethrin has stronger knocking down effect than killing effect.

PMID- 9253893
TI  - Estimation of larval production in Sanjay Lake and its surrounding ponds in
      Delhi, India using remote sensing technology.
AB  - A feasibility study to use remote sensing techniques for estimation of mosquito
      production in Sanjay lake in east Delhi was carried out. Besides the Sanjay lake,
      larval production for 12 surrounding remote sensing identifiable ponds was also
      estimated. Inspite of some limitations the technique is very useful for rapid
      mapping of major breeding sites, recording temporal changes and estimation of
      larval production in a cost effective manner in terms of survey cost and time.

PMID- 9253894
TI  - Pyrethroid insecticide treated bednets for malaria control in the People's
      Republic of China.

PMID- 9253895
TI  - Etiology of acute non-A, B, C hepatitis in Thai patients: preliminary study.
AB  - To better characterize the etiology of acute non-A, B, C hepatitis, 24 sera from
      50 acute hepatitis without acute markers for hepatitis A, B, and C were examined
      for acute markers for the hepatitis E virus (HEV), cytomegalovirus (CMV), herpes
      simplex virus type 2 (HSV-2), and Epstein-Barr virus. Immunoglobulin M (IgM)
      specific for HEV, HSV-2, and CMV was detected using ELISA and total Ig specific
      to EBV was determined by standard indirect immunofluorescence. IgM to CMV was not
      observed in sera from any of the patients; whereas, IgM to HEV was detected in
      sera from 2 patients and IgM to HSV-2 was detected in 5 of 24 acute hepatitis
      patients. In addition, high titer of antibody was found in 2 of the patients.
      This results indicate that HSV-2 and HEV circulate in Thailand and are
      responsible for a small proportion of non-A, B, C hepatitis in Thailand.

PMID- 9253896
TI  - Potential transmission of Bancroftian filariasis in urban Thailand.

PMID- 9253897
TI  - Prevalence of Blastocystis in animals from domesticated surroundings.

PMID- 9253898
TI  - First report of Suidasia pontifica (Acari : Acaridae) in milk powder.

PMID- 9253899
TI  - Differential performance of TRISS-like in early and late blunt trauma deaths.
AB  - OBJECTIVES: (1) To independently validate the Trauma and Injury Severity Score
      Like (TRISS-Like) model derived by Offner et al. (Revision of TRISS for intubated
      patients. J Trauma. 1992;32:32-35) in a population of Canadian blunt trauma
      victims, and (2) to compare the ability of this model to predict mortality in
      early and late trauma deaths. STUDY POPULATION: Prospective cohort of blunt
      trauma cases with Injury Severity Score > 12 identified from the Ontario Trauma
      Registry over a 5-year period. STUDY DESIGN: The TRISS-Like model consisting of
      age, Injury Severity Score, systolic blood pressure, and best motor response of
      the Glasgow Coma Scale was evaluated as to its ability to predict mortality by
      determining the sensitivity, specificity, and the area under the receiver
      operating characteristic curve. The sample was then divided into early (< or = 7
      days) and late mortality subgroups in which model performance was evaluated with
      respect to time of death. RESULTS: A total of 7,703 patients were included in
      this analysis. The overall mortality was 12.3%. The TRISS-Like model allowed for
      assessment of an additional 23% of patients than would standard TRISS and
      performed with a sensitivity of 97.1%, specificity of 39.8% and an area under the
      receiver operating characteristic curve of 0.873. Analysis of mortality with
      respect to time demonstrated that 75% of deaths occurred by day 7. The
      specificity and receiver operating characteristic area increased in the early (<
      or = 7 days) subgroup, 46.5% and 0.935, respectively, compared with 20.8% and
      0.778 in the late mortality group. CONCLUSIONS: TRISS-Like demonstrated similar
      performance to that reported with the standard TRISS model but with the
      additional advantage that it is more generalizable because it can be applied to
      intubated patients. TRISS-Like demonstrated substantially superior performance in
      early trauma deaths compared with those that occurred late. This differential
      performance may be because the model does not include risk factors for late
      mortality.

PMID- 9253900
TI  - Estimation of condensed pulmonary parenchyma from gas exchange parameters in
      patients with multiple trauma and blunt chest trauma.
AB  - Pulmonary gas exchange in correlation with condensed lung volume was
      prospectively studied in 10 patients with multiple injuries and blunt chest
      trauma. The purpose was to find nomograms that allow the estimation of the extent
      of pulmonary density from gas exchange parameters. The condensed lung volume was
      determined planimetrically from serial transverse sections of chest computed
      tomographic scans. There was no correlation between condensed lung volume and
      mean pulmonary artery pressure, pulmonary vascular resistance, systemic vascular
      resistance, or cardiac index and a week negative correlation to the oxygenation
      index (PaO2/FIO2) (r2 = 0.46) and to the total static lung compliance (r2 =
      0.29). A strong correlation between pulmonary density and intrapulmonary shunt
      fraction (Qs/Qt) (r2 = 0.95) as well as alveoloarterial PO2 difference (P[A-a]O2)
      (r2 = 0.86) was evident. By using linear regression equations (linear regression
      line with 95% confidence interval), nomograms were calculated. The extent of
      pulmonary density can easily be obtained from these nomograms by measuring Qs/Qt
      or P(A-a)O2. The presented nomograms may be helpful in monitoring the effect of
      treatment in patients with blunt chest trauma.

PMID- 9253901
TI  - Computed tomography of the chest in blunt thoracic trauma: results of a
      prospective study.
AB  - BACKGROUND: Computed tomography of the chest (CTC) is more sensitive than
      conventional roentgenography at detecting blunt thoracic injuries. Its effect on
      subsequent therapy remains incompletely characterized. METHODS: Nine criteria
      believed to represent the presence of, or the potential for, significant thoracic
      injuries were defined, and patients were followed prospectively. Forty
      consecutive patients had CTC after initial evaluation. Physiologic and anatomic
      findings were compared, and the effect of CTC on therapy was analyzed. RESULTS:
      CTC detected 76 injuries not found on plain roentgenograms, and plain
      roentgenograms detected 25 injuries not visible on CTC scans. Six patients had
      therapy changes based on CTC findings, five of which involved chest tube
      modification. The percentage of pulmonary contusion did not predict the need for
      mechanical ventilation but did correlate with physiologic contusion. CONCLUSIONS:
      Blunt thoracic injuries detected by CTC infrequently require immediate therapy.
      If immediate therapy is needed, findings will be visible on plain roentgenograms
      or on clinical exam. Routine CTC in blunt trauma is not recommended but may be
      helpful in selected cases.

PMID- 9253902
TI  - Cardiac herniation producing tamponade: the critical role of early diagnosis.
AB  - BACKGROUND: Rupture of the pleuropericardium (PP) occurs rarely, with most
      patients dying of associated injuries before arriving at the hospital. Among
      patients who initially survive, the diagnosis is often delayed until cardiogenic
      shock secondary to cardiac herniation is evident. METHODS: The records of 10
      patients with PP lacerations and cardiac herniations were reviewed. RESULTS: All
      but one patient had a normal chest x-ray (CXR) film on admission. After the
      patients became symptomatic, seven of nine had abnormal findings on CXR film
      demonstrating herniation of the heart into the left hemithorax. The other two
      patients underwent surgery without a repeat CXR film. Except for one who was
      taken directly to the operating room, all patients had been previously stabilized
      before developing cardiogenic shock, on average 9 hours after admission.
      Operative therapy was closure of the pericardium for five patients and completion
      pericardiotomy for the others. All survivors developed significant complications,
      and four of them died. CONCLUSIONS: The diagnosis of PP rupture should be
      considered for patients with multiple trauma who develop sudden and unexpected
      cardiogenic shock after their initial condition has been stabilized. A repeat CXR
      film is diagnostic in most cases and should be used as the most efficient and
      expeditious route to making the diagnosis.

PMID- 9253903
TI  - Thoracic trauma and early intramedullary nailing of femur fractures: are we doing
      harm?
AB  - INTRODUCTION: It has been reported that early intramedullary nailing (IMN) of a
      femur fracture in the presence of thoracic injury increases morbidity and
      mortality. The purpose of the present study was to determine if IMN < or = 24
      hours after multisystem injury (Injury Severity Score (ISS) > 16) is associated
      with a poor hospital outcome in the presence of blunt thoracic trauma
      (Abbreviated Injury Scale (AIS) thorax score > or = 2). METHODS: Retrospective
      cohort study at a single adult trauma center. RESULTS: In a 6-year period, 149
      blunt trauma patients had both an ISS > 16 and a femur fracture managed by IMN.
      These 149 patients were divided into four groups based on thoracic injury (T =
      AIS thorax score > or = 2; N = AIS thorax score < 2) and the timing of IMN (E = <
      or = 24 hours; L = > 24 hours). There were 68 TE, 57 NE, 15 TL, and 9 NL
      patients. The TE and NE groups were similar in age and ISS. TE and NE groups had
      similar durations of ventilation, critical care, hospital stay, and mortality.
      Furthermore, TE patients were no more likely to be intubated after IMN than NE
      patients. TE patients were matched with similar patients without a femur fracture
      and found to have similar hospital outcomes. CONCLUSIONS: This study has not
      demonstrated an increased morbidity or mortality associated with early IMN in the
      presence of thoracic trauma.

PMID- 9253904
TI  - Retinal large vessel oxygen saturations correlate with early blood loss and
      hypoxia in anesthetized swine.
AB  - BACKGROUND: Noninvasive monitoring would likely improve trauma care. Using laser
      technology, we monitored the oxygen saturation in retinal vessels during
      exsanguination and hypoxia. METHODS: Seven anesthetized swine were bled at 0.4
      mL/kg/min for 40 minutes. During exsanguination, retinal venous saturation
      (SrvO2) was measured using an eye oximeter, and central venous saturation (SvO2)
      was measured using a fiber-optic catheter. After the shed blood was reinfused,
      the FiO2 was progressively decreased from 0.97 to 0.07. Femoral artery oxygen
      saturation (SaO2) and retinal artery oxygen saturation (SraO2) were measured at
      each increment. RESULTS: During exsanguination, SrvO2 correlated with blood loss
      (r = -0.93) and SvO2 (r = 0.94). SraO2 correlated with SaO2 during incremental
      hypoxia (R2 = 0.93 +/- 0.15). CONCLUSIONS: In this model of exsanguination,
      retinal venous oxygen saturation correlates with blood volume and with central
      venous oxygen saturation. The SraO2 correlates with SaO2 during graded hypoxia.
      Use of an eye oximeter to noninvasively monitor trauma patients appears promising
      and warrants further study.

PMID- 9253905
TI  - Laser Doppler evaluation of burned hands predicts need for surgical grafting.
AB  - Management of deep dermal hand burns represents a difficult clinical problem for
      the burn team because bedside estimation of burn depth is unreliable. Early
      identification of full-thickness injury and prolonged healing times might result
      in the decision to perform surgical excision of eschar and skin grafting of the
      wounds. Such a strategy may improve overall functional and cosmetic results of
      hand burn treatment. This report concerns a 2-year study of 31 patients with 43
      burned hands using the LD6000 helium-neon laser Doppler flowmeter. After
      obtaining informed consent, burned areas of the hand were evaluated on days 1, 3,
      and 5 after burn. Results were reported as flow (mV), representing the quantity
      of moving erythrocytes multiplied by erythrocyte velocity in the capillary
      tissue. The reported volume in percentage of Doppler-shifted light represented
      only the quantity of moving erythrocytes. Median flow values in nongrafted hands
      were 150 mV; in those requiring skin grafts, median flow values were 89 mV. Flow
      values were significantly greater in nongrafted compared with grafted hand burns
      on days 1 and 5. Volume values were not associated with whether or not grafting
      was performed. Median volume values, however, did allow determination of whether
      the burns would spontaneously heal within 15 days (high group) or if a mean of 42
      days would be required (low group). Functional and cosmetic outcomes were
      determined by retrospective chart review, which revealed comparable results
      regardless of grafting and regardless of short or prolonged healing times. Laser
      Doppler flowmetry may serve as a valuable adjunct to the prediction of the need
      for grafting and time to wound closure. Standardization of flowmetry data and
      techniques of evaluation are desirable. Spontaneous healing should be the goal in
      the majority of deep dermal hand burns.

PMID- 9253906
TI  - Manipulation of the inflammatory response to burn injury.
AB  - BACKGROUND: Burn injury is characterized by hypermetabolism and protein
      catabolism. Endotoxin, derived from either wound or gut, may participate in this
      response. METHODS: Eleven seriously burned patients were treated with the
      endotoxin-binding agent polymyxin B and underwent partitional calorimetry and
      nitrogen balance studies. The data from theses patients were compared with data
      from 28 contemporary, similarly burned patients who did not receive polymyxin B.
      RESULTS: Elevated levels of circulating endotoxin were not consistently detected
      in either group. Interleukin-6 was elevated and correlated with rectal
      temperature and nitrogen excretion in both groups. Administration of polymyxin B
      produced no change in metabolic rate but produced a significantly more positive
      nitrogen balance and was associated with a prompt reduction in interleukin-6
      levels. CONCLUSIONS: These data support the hypothesis that endotoxin plays a
      role in the postburn protein catabolism but not in the hypermetabolic response.
      This protein catabolic response is statistically associated with circulating
      interleukin-6 levels, suggesting a possible role for interleukin-6 in postinjury
      protein wasting.

PMID- 9253907
TI  - Oxandrolone, an anabolic steroid, significantly increases the rate of weight gain
      in the recovery phase after major burns.
AB  - We studied the effect of an anabolic steroid, oxandrolone, combined with a high
      protein diet (2 g/kg/day) on the rate of weight gain and restoration of muscle
      function in the recovery phase after deep burns of 30 of 50% of total body
      surface (n = 7). The findings were compared with findings from an isocaloric (2
      g/kg/day protein) diet alone (n = 6). The study was prospective and randomized.
      Data were also compared retrospectively with data from a group of burn patients
      treated in the same fashion using a high-calorie, high-protein diet with a
      protein content of 1.3 to 1.4 g/kg/day (n = 10). Muscle function was quantified
      using a physical therapy index defining rate of progress (0 = lowest, 10 =
      highest). Oxandrolone was given in the beginning of the recovery phase in a
      dosage of 10 mg orally twice a day. The recovery phase was defined as resolution
      of the hypermetabolic state using physiologic criteria. The study was performed
      in an acute burn rehabilitation facility where patients were transferred once
      entering the recovery phase. Patients in each group were not different with
      regard to age and burn size. We found that mean weight loss for all patients was
      11 +/- 2% of preburn weight during the catabolic phase despite optimum nutrition
      and early wound closure. Data are presented as mean +/- SD. We found that the
      average weight gain during the first 3 weeks was 14.5 +/- 2.5 pounds and that the
      physical therapy index was 8.8 +/- 0.5 of recovery in the oxandrolone-protein
      group (n = 7); both of these values were significantly greater than the
      corresponding values in the other groups. In the high-protein alone group (n =
      6), weight gain was 7.5 +/- 1.7 pounds and physical therapy index was 7.0 +/-
      0.8. In the retrospective group (n = 10), weight gain was 4.4 +/- 0.8 pounds and
      function index was 4.1 +/- 0.5. The daily caloric intake was not different
      between groups. Protein content and oxandrolone were the variables. No side
      effects were noted with oxandrolone. We can conclude that an anabolic steroid
      combined with increased protein intake can significantly increase the rate of
      restoration of weight gain postburn.

PMID- 9253908
TI  - A prospective, randomized trial of intravenous fat emulsion administration in
      trauma victims requiring total parenteral nutrition.
AB  - OBJECTIVE: Intravenous fat infusions are a standard component of total parenteral
      nutrition (TPN). We studied the effects of withholding fat infusions in trauma
      patients requiring TPN. DESIGN: Polytrauma patients receiving TPN were randomized
      to receive a standard fat emulsion dose (L) or to have fat infusions withheld
      (NL) for the first 10 days of TPN. The two groups received the same amino acid
      and carbohydrate dose (isonitrogenous, nonisocaloric). MATERIALS AND METHODS:
      Clinical outcome parameters were measured. T-cell function was assessed by
      measuring lymphokine activated killer and natural killer cell activity.
      MEASUREMENTS AND MAIN RESULTS: Demographics including Injury Severity Score (27
      +/- 8; 30 +/- 9) and APACHE II scores (23 +/- 6; 22 +/- 5) were similar for the L
      (n = 30) and NL (n = 27) groups, respectively. Differences (p < 0.05) were found
      in length of hospitalization (L = 39 +/- 24; NL = 27 +/- 16), intensive care unit
      length of stay (L = 29 +/- 22; NL = 18 +/- 12), and days on mechanical
      ventilation (L = 27 +/- 21; NL = 15 +/- 12). The L group had a higher number of
      infections (72 in 30) than the NL group (39 in 27) and T-cell function was
      depressed in this group. CONCLUSIONS: Intravenous fat emulsion infusions during
      the early postinjury period increased susceptibility to infection, prolonged
      pulmonary failure, and delayed recovery in critically injured patients. It is not
      clear whether the improved outcome in the NL group was directly related to
      withholding the fat infusions or due to the hypocaloric nutritional regimen
      (underfeeding) these patients received.

PMID- 9253909
TI  - Secondary emergency department triage (supertriage) and trauma team activation:
      effects on resource utilization and patient care.
AB  - BACKGROUND: Not all field triage patients need full trauma team activation.
      Secondary emergency department (ED) triage (supertriage), a clinical and anatomic
      screen, determines trauma team versus ED management. The purpose was to study the
      effects of supertriage on injury severity and disposition by patients managed
      with and without team activation. METHODS: Observational study of consecutive
      patients transported for alert consideration undergoing supertriage by a trauma
      nurse. Chart review was performed for disposition and Injury Severity Score.
      Contingency table or t test with p < or = 0.05 was used for data analysis.
      RESULTS: One hundred ninety patients were screened; 74% of the 54 with positive
      supertriage and team activation needed the operating room in 24 hours or the
      intensive care unit versus 46% of cases with negative supertriage managed in the
      ED and admitted (p = 0.015). Of the 35 admitted ED patients, 10 required the
      operating room and 6 required the intensive care unit. CONCLUSIONS: Supertriage
      identified a majority requiring team activation; however, resources must be
      available for the seriously injured not meeting field or hospital triage
      criteria.

PMID- 9253910
TI  - Financial outcome of treating trauma in a rural environment.
AB  - The financial plight of the urban trauma center is well documented. However, the
      financial status of the rural trauma center is largely unknown. We hypothesized
      that our rural trauma center with a high number of blunt trauma patients, a wide
      spectrum of injury severity, and a large percentage of insured patients would
      prove to be financially advantageous to the institution. From January 1994 to
      June 1995, 1,119 consecutive trauma admissions had a complete financial profile
      compiled including actual costs, reimbursements, and reimbursement ratio (RR =
      reimbursement/actual costs). Our injury severity profile was very skewed with a
      preponderance of less severely injured patients (mean Injury Severity Score = 9.6
      +/- 7.8). The payor profile of these patients included 49.2% fee-for-service (RR
      = 1.43), 25.4% diagnosis-related group-based (RR = 0.92), 8.77% per diem (RR =
      0.51), and 1.25% capitated (RR = 0.47). Overall, the RR for the trauma unit was
      1.11, representing a net profit overall. Cost closely tracked both hospital and
      intensive-care unit length of stay (R2 = 0.925). Likewise, reimbursement also was
      reflected in both hospital and intensive-care unit length of stay (R2 = 0.735).
      We conclude that our rural trauma center, with a favorable payor mix and low
      injury severity, is financially profitable.

PMID- 9253911
TI  - Geographic variations in mortality from motor vehicle crashes in Taiwan.
AB  - Mortality from motor vehicle crashes within five urbanization categories in
      Taiwan between 1981 and 1990 was investigated. Sex-specific standardized
      mortality ratios (SMRs) were calculated within each urbanization category for
      motor vehicle crash deaths. Most urban areas demonstrated lower SMRs for both
      males and females. In contrast, most rural areas exhibited higher SMRs for both
      males and females. Both males and females demonstrated a significant linear
      relationship between decreasing urbanization and increasing SMRs for motor
      vehicle crash mortality. A variety of factors may underlie the inverse
      correlation between SMRs for motor vehicle crashes and urbanization category.
      These data are most useful in generating hypotheses for further studies to define
      specific etiological factors operating within urbanization categories.

PMID- 9253912
TI  - Facial protection conferred by cycle safety helmets: use of digitized image
      processing to develop a new nondestructive test.
AB  - Cycle safety helmets are designed to prevent head injury. Although most
      commercially available helmets conform to one of several national and
      international standards, individual designs differ widely, particularly in
      relation to face coverage. A method was developed to assess the potential for the
      differing designs to protect the face from injury. A nonimpact test was assessed,
      using digitized image-processing software (Digithurst Ltd.) to measure the shadow
      cast by a helmet rim under a collimated plane light source onto the face of a
      mannequin headform. Twelve helmet designs available internationally were tested
      and ranked with respect to the direct protection conferred (area of the face
      directly covered by the helmet) and indirect protection (area of the face
      shaded). The three highest-ranking helmets for direct protection (Rosebank
      Stackhat, Asphalt Warrior, and Lazer Voyager) also ranked the highest for
      indirect protection. These helmets were more inferiorly extended and were of a
      more bulky construction. It was concluded that the dimensions of cycle helmets in
      relation to face coverage are crucial in influencing the extent to which facial
      protection is conferred. International test standards need urgent revision to
      ensure that face coverage is optimized. Lower-face protection could be achieved
      through incorporation of a lower-face bar to cycle helmets.

PMID- 9253913
TI  - Are scene flights for penetrating trauma justified?
AB  - OBJECTIVE: To evaluate the medical efficacy of helicopter scene flights for
      patients with noncranial penetrating injuries. DESIGN: A retrospective review of
      122 consecutive victims of noncranial penetrating injuries evacuated by
      helicopter from the scene of injury to a level I trauma center. There were no
      medical criteria for accepting or rejecting a request for a scene flight by any
      public safety agency or emergency medical service (EMS). Flights were dispatched
      if the weather permitted and if a helicopter was available. RESULTS: The majority
      of patients were critically wounded. Their average Revised Trauma Score was 10.6,
      and 15.6% of the patients died (19 of 122), including all 11 patients who
      required prehospital cardiopulmonary resuscitation. Helicopter transport from the
      scene did not hasten trauma center arrival for any of the 122 patients. Ninety
      two of the first-responder EMS units (75.4%) were advanced life support units
      (ALS) with crews of paramedics. The remaining 30 (24.6%) first-responder EMS
      units were basic life support units (BLS) with crews of emergency medical
      technicians (EMTs). Six of 122 patients (4.9%) required medical interventions by
      the medical flight crews beyond the capabilities of the ground EMS personnel.
      Only 3 of the 92 patients (3.3%) treated by first-responding paramedics received
      medical interventions by the medical flight crews beyond those authorized for
      paramedics (one cricothyroidotomy and two needle thoracenteses). Two of the 30
      patients (6.7%) treated by first-responding EMTs received medical interventions
      by the medical flight crews not authorized for the EMTs. The on-scene paramedics
      performed endotracheal intubation on 10 patients. However, because of subsequent
      clinical deterioration, the medical flight crews performed endotracheal
      intubations on nine additional patients. In addition, two patients intubated by
      the first-responding paramedics required reintubation by the medical flight
      crews. CONCLUSIONS: Scene flights in this metropolitan area for patients who
      suffered noncranial penetrating injuries demonstrated that these flights were not
      medically efficacious. This conclusion rests on the findings that arrival at a
      trauma center was not hastened by scene flights and that only 4.9% of patients
      required prehospital care by the medical flight crew beyond the capabilities of
      the first-responding EMS personnel (2.5 and 6.7% for ALS and BLS responders,
      respectively). Based on this experience, we believe that in metropolitan areas,
      scene flights for victims of noncranial penetrating injuries should be restricted
      to critically injured patients likely to require prehospital care by the medical
      flight crew that is beyond the capabilities of the first responders or when the
      scene flight is likely to significantly hasten the arrival of the injured patient
      to an appropriate trauma center.

PMID- 9253915
TI  - Equine-related neurosurgical trauma: a prospective series of 30 patients.
AB  - Thirty million Americans ride horses; 50,000 of these riders are treated in
      emergency rooms annually. Equestrian activities are uniquely dangerous because
      the participant is unrestrained, often helmetless, and riding large,
      unpredictable animals capable of 40-mph speeds and kicking with up to 1 ton of
      force. Neurologic injuries in equestrians constitute the majority of severe
      injuries and fatalities. We prospectively studied all patients admitted to the
      University of Kentucky Medical Center with equine-related neurosurgical trauma
      from July 1992 to January 1996. Eighteen of 30 patients were male. Age ranged
      from 3 to 64 years. Five patients died (17%), and two suffered permanent
      paralysis. There were 24 head injuries (80%) and 9 spinal injuries (30%). The
      majority of injuries (60%) were caused by ejection or fall from the horse. Twelve
      patients (40%) were kicked by a horse, and four patients sustained crush
      injuries. Six patients underwent craniotomy, three had operative spinal
      stabilization, and five required ventriculostomy. Eleven patients (37%) were
      professional riders. Twenty-four patients (80%) were not wearing helmets,
      including all fatalities and craniotomy patients. Our data show that equine
      related neurosurgical injuries can be severe and fatal because of the significant
      size, force, and unpredictability of these animals as well as the lack of proper
      headgear. We recommend that helmets be worn at all times around horses because a
      significant number of our patients (33%) were injured as bystanders. Risk of
      serious injury appears to be a function of cumulative exposure to horses, not
      level of expertise. Experience is not protective; helmets are.

PMID- 9253914
TI  - Injury rates in children participating in taekwondo competition.
AB  - OBJECTIVE: To report rates of injuries sustained during Junior taekwondo
      competitions. DESIGN: Prospective. MATERIALS AND METHODS: Data were collected
      with simple check-off forms that describe the athlete, nature, site,
      circumstances, and severity of the injury at three major taekwondo tournaments
      involving a total of 3,341 boys and 917 girls. MAIN RESULTS: No difference was
      found between boys (58.34/1,000 athlete-exposures) and girls (56.57/1,000 athlete
      exposures) in total injury rate (p > 0.05). Collapsed over gender, significant
      differences (p = 0.013) in injury rates of body parts were found with the lower
      extremities (21.83/1,000 athlete-exposures) ranked first. Unblocked attacks are
      the major cause of injury in both boys and girls. CONCLUSIONS: Coaches are
      advised to work on the blocking skills of their Junior taekwondo athletes. No
      head contact for children in taekwondo competition should also be considered.

PMID- 9253916
TI  - Pediatric hand injuries due to exercise bicycles.
AB  - METHODS: This is a 5-year retrospective review of hand injuries caused by
      exercise bicycles among 34 children. RESULTS: Mean age was 3 years and 5 months.
      Accidents were caused most commonly by impingement of the fingers between the
      chain and sprocket wheel (77%), but injuries caused by spinning wheel spokes
      (23%) were generally more severe. Injuries were usually of the avulsion type and
      ranged in severity from lacerations (43%) to fractures (19%) to amputations
      (38%). The central digits (87%) were involved more frequently than the border
      digits (13%). Replantation was possible for 33% of the amputated digits, with 50%
      of the fingers surviving. CONCLUSION: The avulsive nature of these injuries
      should be taken into consideration when attempting replantation. Increased
      community awareness and equipment safety modifications are needed to eliminate
      this preventable problem.

PMID- 9253917
TI  - Flexor tendon graft for late management of isolated rupture of the profundus
      tendon.
AB  - BACKGROUND: Late management options for the neglected flexor tendon injury
      include arthrodesis, tenodesis, tendon advancement, or tendon grafting. Although
      the clinical outcomes of single-stage and second-stage flexor tendon grafting are
      satisfactory, many controversies exist. The present study retrospectively
      reviewed the clinical outcomes of flexor tendon grafting for 15 patients with
      isolated profundus rupture. METHODS: Fifteen cases of isolated rupture of the
      flexor profundus tendon were treated by free tendon graft. The age of the
      patients ranged from 13 to 21 years (mean, 17.3 years). The time from injury to
      operation ranged from 4 to 14 weeks (mean, 8.3 weeks). All tendon grafts were
      passed through the intact superficialis tendon to repair the injured profundus
      tendon. These patient were followed up from 14 to 62 months after treatment mean,
      31.3 months). RESULTS: All but one patient had less than 3.2 cm of flexion from
      fingertip to mid-palmar crease. Fourteen patients achieved active distal
      interphalangeal (DIP) joint flexion of more than 20 degrees. Four patients
      developed extension loss of the proximal interphalangeal (PIP) joint of more than
      30 degrees after surgery. The mean active flexion after surgery was 33 degrees
      (range, 15-55 degrees) for DIP joints and 91.3 degrees (range, 80-100 degrees)
      for PIP joints. Three patients had combined extension loss of PIP and DIP joints
      of more than 40 degrees for the index and middle fingers. Twelve patients (80%)
      had satisfactory results, whereas treatment of the other 3 patients was
      considered unsuccessful. CONCLUSION: Flexor tendon graft can be used to
      reconstruct the isolated rupture of the profundus tendon and achieve satisfactory
      results for properly selected patients.

PMID- 9253918
TI  - Retained foreign bodies.
AB  - OBJECTIVE: To evaluate the frequency of occurrence and outcome of patients having
      retained foreign bodies after treatment in an urgent-care setting. MATERIALS AND
      METHODS: Closed case records from the files of the Medical Professional Mutual
      Insurance Company involving claims of retained foreign body were reviewed for a 7
      year period. MAIN RESULTS: Thirty-two patients filed 54 claims against 32
      physicians and 22 health care institutions. Defense costs were $298,906, and
      indemnity payments were $1,279,171. Glass was the most frequent retained foreign
      body, constituting 53% of claims. Despite the fact that glass is radiopaque, x
      ray films were ordered for only 35% of these patients. Retention of glass
      fragments when no radiologic study was obtained resulted in unsuccessful defense
      of 60% of the claims and higher indemnity payments. Radiologic studies were
      ordered for only 31% of all patients. CONCLUSIONS: All wounds should be
      considered to be at risk for foreign body entry. Documentation in the medical
      record of wound exploration and patient follow-up, and ordering of plain films
      and other diagnostic imaging studies should be used more frequently toward this
      end.

PMID- 9253919
TI  - Treatment of femoral shaft aseptic nonunions: comparison between closed and open
      bone-grafting techniques.
AB  - OBJECTIVE: The aim of this prospective study was to investigate and compare the
      effects of closed and open bone-grafting techniques in the treatment of femoral
      shaft aseptic nonunions. MATERIALS AND METHODS: Forty consecutive femoral shaft
      aseptic nonunions with inserted reamed intramedullary nails were randomly divided
      into two groups. The indications for these techniques were aseptic nonunions with
      less than 1 cm of shortening, no rotational or angular misalignment, and no large
      bony defects. The closed technique consisted of intramedullary reaming to a
      larger size and reinsertion of a stable intramedullary nail. The open technique
      consisted of local debridement, maintaining local stability with or without
      supplementation, and upper tibial cancellous bone grafting. RESULTS: Thirty-five
      cases were followed up for at least 1 year (range, 1-3 years), and all achieved
      solid unions. There were no significant complications. The union period with the
      closed technique was significantly shorter than with the open technique (4.0 +/-
      0.6 months vs. 5.1 +/- 0.8 months; p < 0.01, Student's t test). The operating
      time with the closed technique was also significantly shorter than with the open
      technique (36 +/- 7 minutes vs. 58 +/- 14 minutes; p < 0.01, Student's t test).
      There was no significant difference in other parameters between the two
      techniques. CONCLUSIONS: The closed bone-grafting technique had clinical results
      similar to those of the open technique. The surgical procedure was simpler,
      however, and the union period was shorter. Whenever possible, therefore, the
      closed technique should be considered in all indicated cases.

PMID- 9253920
TI  - Specific features associated with femoral shaft fractures caused by low-energy
      trauma.
AB  - OBJECTIVE: To scrutinize the fracture patterns of femoral shaft fractures caused
      by low-energy injury mechanism and to delineate the problems associated with the
      treatment of these fractures. MATERIALS AND METHODS: Of a total of 192
      consecutive skeletally mature patients with 201 acute fresh femoral shaft
      fractures admitted during a 10-year period (1985-1994), 50 patients had a
      fracture caused by low-energy trauma. The fractures were classified in terms of
      their configuration, site, degree of comminution, and soft-tissue injury. The
      previous fractures, chronic illnesses, and continuous medications of the patients
      as well as the injury mechanisms and concomitant injuries were registered. All
      general and local complications and their consequences were recorded. Forty
      patients could be followed until the bony union of the fracture was achieved, the
      mean follow-up time being 14 months. RESULTS: The incidence of these injuries was
      2.5 per 100,000 person-years. There were 32 women and 18 men. The mean age of the
      patients was 65 years (range, 17-92 years). Thirteen patients were younger than
      60 years of age. Thirty-two (64%) had at least one local or general factor
      weakening the mechanical strength of the bone that predisposed them to a
      fracture. Thirty-two patients sustained a fracture of the left femur (p < 0.05).
      All fractures were closed. None of the patients had significant concomitant
      injuries. In 33 cases, the site of the fracture was in the middle third of the
      femur. The fracture configuration was spiral in 29, transverse in 10, oblique
      transverse in 7, and oblique in 4 cases. Postoperative complications, including
      delayed union, nonunion, and malunion, occurred with 29 patients. Eighteen
      reoperations among 12 patients were performed because of these complications.
      CONCLUSIONS: Femoral shaft fractures caused by low-energy violence occur mainly
      in patients suffering from a chronic disease or a condition causing osteopenia of
      the femur. The most common fracture pattern was a spiral one in the middle third
      of the femoral shaft. Despite the low-energy violence, the treatment of these
      fractures is not devoid of complications. The treatment of these seemingly simple
      fractures requires careful planning and meticulous operative technique.

PMID- 9253921
TI  - Previous trauma as a risk factor for recurrent trauma in rural northern Israel.
AB  - BACKGROUND: Recently, a few urban trauma centers reported on repetitiveness of
      injury in some population groups. The aim of this study is to evaluate the
      concept of "trauma recidivism" by measurement of the association of previous
      trauma events with acute trauma in a rural region of northern Israel with a
      specific sociocultural population mixture, low drug and alcohol abuse, and low
      levels of criminal activity. METHODS: A case-control study was conducted
      comparing 100 consecutive trauma cases with selected controls. The main predictor
      variable evaluated in this study was a history of previous significant traumatic
      events. Cases were defined as patients > 14 years of age hospitalized for acute
      trauma. Controls were selected from hospitalized patients with nontraumatic
      conditions. Logistic regression analysis was performed to adjust for potential
      sociodemographic confounding factors. RESULTS: The trauma group was significantly
      younger (p < 0.001) and predominantly male (p < 0.03). The incidence of
      "recurrent trauma" was highly significant in this group (p < 0.00001), and
      "injury-free intervals" were significantly shorter (p < 0.002). A history of
      previous significant traumatic events was a strong predictor for recurrent trauma
      (adjusted odds ratio, 10.36; 95% confidence interval, 3.10-34.58). Injury types
      and patterns differed in subgroups, although the demographic structure of the
      trauma recidivists group conformed to that of the general population.
      CONCLUSIONS: In this limited population study from rural northern Israel, a
      previous history of significant trauma is associated with recurrent trauma.
      Sociodemographic and cultural factors do not appear to be strong predictors for
      recurrent trauma. Further research investigating trauma recidivism is needed to
      clarify these relationships.

PMID- 9253923
TI  - Intrahepatic vascular clamping in complex hepatic vein injuries.

PMID- 9253922
TI  - Ligation: an alternative for control of exsanguination in major vascular
      injuries.
AB  - BACKGROUND: Temporization in the management of patients in extremis has gained
      acceptance in trauma surgery. Resection, without anastomosis, in major visceral
      injuries followed by delayed reconstruction has been successful. METHODS: To
      evaluate this approach in patients with substantial vascular trauma, we reviewed
      our experience of five patients with major vascular injuries that were ligated as
      a temporizing procedure during a 58-month period. If the patient was hypothermic,
      acidotic, and potentially or actually coagulopathic with significant blood loss,
      achieving expeditious hemostasis was the primary consideration. After hemodynamic
      resuscitation, warming, and correction of the coagulation profile, if necessary
      the patients were returned to the operating room for definitive reconstruction.
      RESULTS: All patients survived; only two required subsequent vascular
      reconstruction. CONCLUSIONS: The prompt control of hemorrhage must be the first
      objective of treatment in critically injured patients. Ligation of major vessel
      injury is a therapeutic alternative as part of the "damage control" philosophy.

PMID- 9253924
TI  - Preservation of reflex movement in a pediatric patient with a complete spinal
      cord injury: case report.

PMID- 9253925
TI  - Isolated avulsion of the middle colic artery with colonic infarction after blunt
      abdominal trauma.

PMID- 9253926
TI  - Spontaneous anterior and lateral tibial compartment syndrome in a type I diabetic
      patient: case report.
AB  - We report the case of a 46-year-old man with type I diabetes who spontaneously
      developed compartment syndrome of the anterior and lateral compartment of the
      left leg. The patient was treated with two compartment fasciotomies.

PMID- 9253927
TI  - An unusual cause of thoracic outlet syndrome.

PMID- 9253928
TI  - Subcoracoid trapping of the proximal fragment of a fractured clavicle.
AB  - An unusual indication--not previously reported--for surgical treatment of a
      clavicle fracture, in a 56-year-old male, is presented. The proximal fragment had
      been entrapped under the coracoid, and there were symptoms from impairment of the
      musculocutaneous nerve. Reduction by closed means proved unsuccessful, and an
      open procedure was necessary for this rare type of the common clavicle fracture.

PMID- 9253929
TI  - Pseudoaneurysm of the superior gluteal arterial system: an unusual cause of pain
      after a pelvic fracture.
AB  - This case report describes a complication after treatment of a rotationally
      unstable pelvic fracture: a pseudoaneurysm of the superior gluteal arterial
      system. The patient sustained an anterior-posterior compression pelvic fracture
      that was stabilized with anterior symphyseal plating and percutaneous iliosacral
      screw insertion. The etiology of the pseudoaneurysm was likely multifactorial,
      including the injury (anterior-posterior compression pelvic fracture), prolonged
      coagulation parameters during administration of warfarin, and the percutaneous
      insertion of an iliosacral lag screw. A pseudoaneurysm of the superior gluteal
      arterial system should be included in the differential diagnosis of unexplained
      pelvic or buttock pain after a pelvic fracture.

PMID- 9253930
TI  - Common carotid artery and tracheal injury from shoulder strap seat belt.
AB  - Carotid artery injuries from seat belt shoulder straps have been reported
      involving primarily the internal carotid artery. This paper describes a case of
      common carotid artery disruption and tracheal transection after a shoulder strap
      seat belt injury. A successful method for management of this rare injury is
      presented. Repair involved autogenous arterial replacement in a contaminated
      field using an interposition graft of superficial femoral artery.

PMID- 9253931
TI  - An unusual case of nail gun injury: penetrating neck wound with nail retention in
      the right pleural cavity.

PMID- 9253932
TI  - Bilateral cervical rib fracture secondary to blunt trauma.

PMID- 9253933
TI  - Delayed presentation of 50 years after a World War II vascular injury with
      intraoperative localization by duplex ultrasound of a traumatic false aneurysm.
AB  - A case of delayed presentation of a traumatic false aneurysm in the left arm 50
      years after penetrating injury sustained during World War II is described. The
      original injury resulted in brachial artery occlusion and complete median nerve
      palsy. The false aneurysm presented with a spontaneous, contained rupture.
      Surgical repair was performed after duplex ultrasound localization of the lesion
      to a small collateral artery lateral to the elbow, thereby avoiding dissection in
      the densely scarred tissue plains in the antecubital fossa. Duplex ultrasound was
      also used intraoperatively to facilitate localization of the aneurysm neck and to
      confirm absence of flow in the sac after repair. A brief historical review of
      traumatic false aneurysms caused by combat injuries, is provided. The progress in
      the treatment of such injuries gained by wartime experience is reviewed.

PMID- 9253934
TI  - Biliary-pleural fistula presenting as a massive pleural effusion after
      thoracoabdominal penetrating trauma.

PMID- 9253935
TI  - Abdominal vascular injuries.
AB  - Trauma surgeons are occasionally faced with patients with abdominal vascular
      injuries. Important surgical issues in the successful management of these
      injuries require a thorough knowledge of the abdominal vascular anatomy and
      techniques of vascular repair, that surgical exploration be performed without
      delay, that the vascular injury be exposed rapidly with control of hemorrhage
      upon entering the abdomen, that efforts be made to reestablish perfusion
      initially to the structures at the highest risk of anoxic injury, and an
      understanding that it is occasionally necessary to perform temporary procedures
      while the general condition of a patient is being stabilized, with subsequent
      definitive care. The primary goal in the management of these patients should be
      hemorrhage control rather than maintenance of blood flow. The principles of
      abbreviated laparotomy with planned reoperation should be used in some patients
      with major abdominal vascular injuries. The decision to reestablish vascular
      continuity at a later time should balance anticipated functional outcome against
      potential complications.

PMID- 9253936
TI  - Traumatic plastic bowing of bones.

PMID- 9253937
TI  - Statistical analysis in Abbreviated Injury Scale does not reflect the added
      morbidity of multiple lower extremity fractures (J. Trauma 1996; 40; 951)

PMID- 9253938
TI  - Tension pneumothorax.

PMID- 9253939
TI  - Negative pressure pulmonary edema (NPPE)

PMID- 9253940
TI  - Self-inflicted injuries before arrival of Hale-Bopp comet.

PMID- 9253941
TI  - Carbamazepine normalizes the altered behavioral and neurochemical response to
      stress in benzodiazepine-withdrawn rats.
AB  - Rats chronically treated with diazepam (2 mg/kg per day, i.p.) for 21 days were
      tested 96 h after the last injection in both the forced swim test (inescapable
      stress) and in an active avoidance test (escapable stress). The influence of
      carbamazepine (7.5 mg/kg, i.p.) administered 25 min prior to each behavioral task
      was investigated. Withdrawn animals showed a reduced time spent in immobility in
      the forced swim test and an enhanced latency to escape in the active avoidance
      test. Both behavioral effects were normalized by a single carbamazepine
      administration. An additional experiment was performed to investigate the effect
      of a forced swim experience on cortical chloride uptake following GABA (gamma
      aminobutyric acid) stimulation 96 h after diazepam withdrawal, and the influence
      of a single administration of carbamazepine on these effects. An increased
      chloride uptake was observed in vehicle-treated rats but not in diazepam
      withdrawn animals following the swimming experience. Carbamazepine pretreatment
      enhanced chloride uptake after diazepam withdrawal but did not modify chloride
      flux in stressed or unstressed vehicle-treated rats. These results support the
      hypothesis that diazepam withdrawal affects the ability to develop adaptive
      responses to stress and that carbamazepine can normalize such an alteration.

PMID- 9253942
TI  - Mazindol and lidocaine are antinociceptives in the mouse formalin model:
      involvement of dopamine receptor.
AB  - The antinociceptive potential of mazindol, an anorectic drug, and lidocaine, an
      amide-type local anesthetic, were investigated in the mouse formalin test with
      concurrent motor function assessment. In addition, the role of dopamine and
      opioid receptors in mediation of the antinociceptive action of these drugs was
      examined. The i.p. injection of mazindol (1.25-10 mg/kg) and lidocaine (10-30
      mg/kg) induced significant antinociceptive responses in both phases of the test.
      Cocaine (20 mg/kg, i.p.), used as positive control, also inhibited the pain
      responses caused by formalin. Haloperidol (0.2 mg/kg, i.p.), and sulpiride (5
      mg/kg, i.p.), a dopamine D2 receptor antagonist, reduced the antinociceptive
      actions of mazindol and cocaine, while SCH 23390, R(+)-7-chloro 8-hydroxy-3methyl
      1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine (0.03 mg/kg, i.p.), a dopamine D1
      receptor antagonist, did not affect these responses. Only the antinociception
      associated with mazindol was reversed by naloxone (2 mg/kg, i.p.). The same
      pretreatments failed to modify lidocaine-induced antinociception. The drug
      conditions used in this study did not reveal any motor impairment in the rotarod
      test. These observations suggest an involvement of dopaminergic mechanisms,
      mainly via dopamine D2 receptors, in the antinociceptive action of mazindol in
      the formalin test, but the nature of mechanisms involved in the lidocaine
      responses remains unsolved.

PMID- 9253943
TI  - Peripheral adenosine 5'-triphosphate enhances nociception in the formalin test
      via activation of a purinergic p2X receptor.
AB  - The pronociceptive effects of adenosine 5'-triphosphate (ATP) were examined in
      the low concentration formalin model (0.5%) by coadministration of ATP, ATP
      analogs (alpha,beta-methylene-ATP and 2-methylthio-ATP) and antagonists (suramin,
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) with formalin and
      determining effects on the expression of flinching behaviours. Coadministration
      of ATP (5-500 nmol) with formalin enhanced phase 2 (12-60 min after injection)
      but not phase 1 (0-10 min after injection) responses. alpha,beta-methylene-ATP
      (0.5-50 nmol) but not 2-methylthio-ATP (50-500 nmol) produced a similar
      enhancement of activity, generating an order of potency of alpha,beta-methylene
      ATP, ATP >> 2-methylthio-ATP. This enhancement was primarily expressed in the
      latter part of phase 2, 30-60 min after injection. Coadministration of suramin 50
      500 nmol, a non-selective P2X and P2Y purinoceptor antagonist and
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid 5-500 nmol, a selective P2X
      purinoceptor antagonist, dose-dependently inhibited the augmentation of the
      formalin response by ATP 50 nmol, but did not reduce the response to formalin
      itself. Pretreatment for 30 min with higher doses of suramin inhibited the
      response to formalin (0.5%, 1.5%) and this appeared to be by a systemically
      mediated action as it was seen following administration into the contralateral
      paw. The results of this study provide evidence in support of a P2X purinoceptor
      mediated augmentation of the pain signal by ATP. The delayed time-course of the
      effect suggests that it may occur in concert with other mediators that are
      recruited by the inflammatory process, rather than reflecting a direct
      depolarization of sensory nerves. Other behavioural paradigms may be required to
      examine the fast onset, direct effect. Suramin appears to exert both local and
      systemic effects on the expression of pain behaviours in response to formalin.

PMID- 9253944
TI  - Mutual dependence of calcitonin-gene related peptide and acetylcholine release in
      neuromuscular preparations.
AB  - To investigate the mutual dependence of calcitonin gene-related peptide (CGRP)
      and acetylcholine release, we examined the effect of a cholinesterase inhibitor
      neostigmine on the release of CGRP-like immunoreactivity in rat phrenic nerve
      hemidiaphragm muscle preparation, and conversely, the effect of CGRP on
      [3H]acetylcholine release from motor nerve terminals loaded with [3H]choline in
      the same preparations of mice. Release of CGRP-like immunoreactivity was
      increased by electrical nerve stimulation (train of 40 pulses of 200 micros pulse
      duration and frequency of 50 Hz applied every 10 s) in the whole preparation but
      not in the segmental preparation containing the endplate region. Neostigmine (0.1
      0.3 microM) enhanced the resting release of CGRP-like immunoreactivity in a
      concentration-dependent manner, whereas it depressed the nerve-evoked release of
      CGRP-like immunoreactivity. CGRP (1 microM) added to perfusate decreased nerve
      evoked [3H]acetylcholine release. These results suggest that CGRP, which is
      released by electrical nerve stimulation or a cholinesterase inhibitor in intact
      skeletal muscles, negatively modulates nerve-evoked acetylcholine release.

PMID- 9253946
TI  - The effect of 3-acetylpyridine on inferior olivary neuron degeneration in Lurcher
      mutant and wild-type mice.
AB  - Lurcher mutant and wild-type mice were given intraperitoneal injections of 3
      acetylpyridine to look at the toxic effects of this drug on the inferior olivary
      neurons. Intraperitoneal administration of 3-acetylpyridine is characterized by
      the different sensitivity of inferior olivary neurons in Lurcher mutant and wild
      type mice. Lurcher mutants suffered a destruction of these neurons while wild
      type mice were unaffected. The results show that there is a different effect of 3
      acetylpyridine between genetic mutations and wild-type mice on the same inbred
      strain of mice. The different affinity of 3-acetylpyridine for the inferior
      olivary neurons of this mutant is briefly discussed.

PMID- 9253945
TI  - Neuropeptide FF receptors control morphine-induced analgesia in the
      parafascicular nucleus and the dorsal raphe nucleus.
AB  - The ability of (1DMe)Y8Fa (D.Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), a
      selective neuropeptide FF analog resistant to enzymatic degradation, to control
      morphine-induced analgesia was investigated in rat after microinfusion into the
      dorsal raphe nucleus and the nucleus parafascicularis of the thalamus. Infusion
      of (1DMe)Y8Fa (2.5 nmol) in the nucleus raphe dorsalis did not modify the animal
      response in the tail-immersion test but significantly reversed analgesia induced
      by coinjected morphine (27 nmol). Similarly, (1DMe)Y8Fa (5 nmol) inhibited
      morphine effects in the hot-plate test after co-injection into the parafascicular
      nucleus. Furthermore, (1DMe)Y8Fa injected into the parafascicular nucleus
      attenuated analgesia induced by morphine injected into the nucleus raphe dorsalis
      and similarly, the neuropeptide FF analog in the nucleus raphe dorsalis decreased
      the effects of 27 nmol morphine injected in the parafascicular nucleus. The
      density of neuropeptide FF receptors did not decrease in the nucleus raphe
      dorsalis after lesion of serotonergic neurons by 5,7-dihydroxytryptamine.
      However, after this lesion, (1DMe)Y8Fa injected in the nucleus raphe dorsalis was
      no longer able to modify analgesic effects of morphine in hot-plate and tail
      immersion tests. Similarly, the serotonin (5-HT) depletion induced by a systemic
      administration of para-chlorophenylalanine did not modify morphine analgesia
      microinjected into the nucleus raphe dorsalis and the parafascicular nucleus but
      blocked the ability of (1DMe)Y8Fa to reverse morphine effects in both nuclei.
      These data show that neuropeptide FF exerts anti-opioid effects directly into
      both the nucleus raphe dorsalis and the parafascicular nucleus and acts also at
      distance on opioid functions. Furthermore, anti-opioid effects of neuropeptide FF
      require functional serotonergic neurons although neuropeptide FF receptors are
      not carried on these neurons.

PMID- 9253947
TI  - Interleukin-1beta-induced, nitric oxide-dependent and -independent inhibition of
      vascular smooth muscle contraction.
AB  - Stimulation of vascular smooth muscle by bacterial lipopolysaccharide has been
      shown to produce interleukin-1beta and to induce vasodilation in septic shock. To
      understand the mechanisms of interleukin-1beta-induced relaxation, we examined
      the effects of interleukin-1beta on contractility and cyclic GMP contents of
      vascular smooth muscle. After treatment of the rat aorta with interleukin-1beta
      (20 ng/ml) for 6 h, the cyclic GMP content increased and the contraction induced
      by phenylephrine (1 microM) was partially inhibited. An inhibitor of nitric oxide
      (NO) synthase, N(G)-monomethyl-L-arginine (L-NMMA, 100 microM), prevented the
      inhibitory effect of interleukin-1beta. After treatment with interleukin-1beta
      for 24 h, the phenylephrine-induced contraction was inhibited more strongly.
      Neither L-NMMA (100 microM) nor aminoguanidine (100 microM) reversed the
      inhibition, whereas methylene blue (10 microM) partially reversed the inhibition.
      After treatment with interleukin-1beta for 12 or 24 h, the cyclic GMP content
      increased but to a level lower than that obtained with a 6-h treatment. The
      effects of sodium nitroprusside (1 microM) to inhibit the phenylephrine-induced
      contraction and to increase the cyclic GMP content were markedly suppressed by
      the 24-h interleukin-1beta treatment. In contrast, the 24-h interleukin-1beta
      treatment did not change the ability of 8-bromo-cGMP to relax the phenylephrine
      stimulated aorta. Addition of L-NMMA (1 mM) during the 24 h treatment prevented
      NO production and preserved the sodium nitroprusside-induced cGMP generation by
      interleukin-1beta. The 24 h interleukin-1beta treatment increased the threshold
      concentration of KCl needed to induce contraction without changing the maximum
      contraction. In the presence of 25.4 mM KCl or the non-selective K+ channel
      inhibitor, tetraethylammonium, the inhibitory effect of the 24-h interleukin
      1beta treatment on phenylephrine-induced contraction was restored. These results
      suggest that interleukin-1beta inhibits vascular smooth muscle contraction by a
      time-dependent, dual mechanism. After a 6-h treatment with interleukin-1beta, the
      NO/cyclic GMP system is activated. After a 24-h interleukin-1beta treatment, in
      contrast, the NO/cyclic GMP system may be desensitized and the contraction of
      vascular smooth muscle is inhibited by another mechanism, possibly membrane
      hyperpolarization.

PMID- 9253948
TI  - T-686, a novel inhibitor of plasminogen activator inhibitor-1, inhibits
      thrombosis without impairment of hemostasis in rats.
AB  - The aim of this study was to evaluate the antithrombotic potential of T-686
      ((3E,4E)-3-benzylidene-4-(3,4,5-trimethoxy-benzylidene)-pyrr olidine-2,5-dione),
      a novel inhibitor of plasminogen activator inhibitor-1 (PAI-1), in rat thrombosis
      models. T-686 (0.1-100 mg/kg per day, p.o.) dose dependently decreased the weight
      of venous thrombi induced by a combination of stasis and hypercoagulability. The
      antithrombotic effect was enhanced by repeated administration of T-686. Warfarin
      (0.1 mg/kg per day for 3 days) also prevented thrombus formation. The
      antithrombotic action by warfarin was accompanied by prolongation of coagulation
      time, while no effect on coagulation time was observed in T-686-treated rats. T
      686 lowered the activity of PAI-1 in plasma. In the arterio-venous shunt model,
      pretreatment with T-686 (10 mg/kg per day) or ticlopidine (100 mg/kg per day) for
      8 days inhibited thrombus formation by 33% and 44%, respectively. T-686 had no
      effect on collagen-induced platelet aggregation ex vivo, while ticlopidine
      inhibited platelet aggregation. T-686 did not affect bleeding time at 10-100
      times the antithrombotic dose, while warfarin dose dependently prolonged bleeding
      time at and around the antithrombotic dose. These results suggest that T-686
      prevents thrombus formation in rats without impairment of hemostasis.

PMID- 9253949
TI  - K(ATP) channels do not mediate vasodilation by 3-morpholinosydnonimine in goat
      coronary artery.
AB  - The present study investigated the role of ATP-sensitive potassium (K(ATP))
      channels in mediating relaxation to the nitric oxide (NO) donor, 3
      morpholinosydnonimine (SIN-1) in goat coronary arteries. SIN-1 (10(-8)-10(-5) M)
      caused concentration-dependent relaxations of the coronary artery ring segments
      contracted with K+ (30 mM) with an EC50 of 6.61 x 10(-7) M. Methylene blue (3 x
      10(-6) M) caused a rightward shift in the concentration-response curve of SIN-1
      (10(-8)-3 X 10(-5) M) with a corresponding increase in the EC50 (3.62 x 10(-6) M)
      of the nitrovasodilator. While the K(ATP) channel blocker, glibenclamide (1 and 3
      x 10(-6) M) caused dose-dependent inhibition of vasorelaxations produced by
      pinacidil (10(-8)-10(-4) M), it had no effect on the vasodilations elicited by
      SIN-1 (10(-8)-10(-5) M) in the coronary arterial smooth muscle. Increasing the
      extracellular K+ concentration from 30 mM to 80 mM to reduce the K+ gradient
      across the cell membrane, inhibited the relaxations elicited by pinacidil (10(-8)
      10(-4) M). On the other hand, SIN-1 (10(-8)-10(-5) M)-induced relaxations were
      potentiated in high K+ (80 mM) compared to those observed at K+ (30 mM). These
      results suggest that goat coronary artery vasodilations caused by the NO donor,
      SIN-1, do not involve K(ATP) channels.

PMID- 9253950
TI  - Differential effects of sulindac on renal hemodynamics and function in the rat.
AB  - Renal hemodynamics were studied using an electromagnetic perivascular flow sensor
      in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.)
      sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial
      pressure was significantly decreased (by 15 mmHg) with sulindac (n = 12). In the
      5 mg/kg b.w. sulindac group (n = 7), renal blood flow progressively and
      significantly increased from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during
      concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The
      pressure limits for efficient and no renal blood flow autoregulation remained
      unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac
      group (n = 5), renal blood flow did not change but autoregulatory pressure limits
      were lowered by 10 mmHg 2 h after treatment (P < 0.025). Also, Na+ retention was
      marked. Prostanoid excretion in urine was significantly reduced with either dose
      but basal plasma renin activity was not (about 8 ng/ml per h; n = 15). When
      plasma renin activity was enhanced after a reduction in renal perfusion pressure
      (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by
      10 mg/kg b.w. sulindac (P < 0.05; n = 6). In conclusion, differential effects of
      sulindac on renal hemodynamics, Na+ excretion and plasma renin activity were
      demonstrated. Renal hemodynamic changes could be related in part to the
      cytochrome P-450 arachidonic acid pathway.

PMID- 9253951
TI  - Role of nitric oxide and nitric oxide-independent relaxing factor in contraction
      and relaxation of rabbit blood vessels.
AB  - It has been shown that spontaneous release of nitric oxide (NO) from the vascular
      endothelium attenuates contractile responses of vascular smooth muscles to
      norepinephrine, and that acetylcholine-induced relaxation is mediated by the
      evoked release of NO and endothelium-derived hyperpolarizing factor. Since the
      involvement of these substances (or factors) in mechanical responses is
      heterogeneous among blood vessels, we have investigated the role of these
      substances in agonist-induced contraction and relaxation in 6 rabbit blood
      vessels. Vascular reactivity for the contractile response to norepinephrine was
      potentiated after removal of endothelium and by 100 microM N(G)-nitro-L-arginine
      (L-NA) but not by 80 nM-0.4 microM clotrimazole. This potentiation was most
      marked in the mesenteric artery among the blood vessels tested, suggesting that
      the basal release of NO reduced the contractile response of the vascular smooth
      muscle to norepinephrine in this artery. Acetylcholine-induced relaxation was
      abolished by removal of the endothelium and was attenuated by L-NA (1-100 microM)
      in all blood vessels. The attenuation by 100 microM L-NA was most obvious in
      aorta and vein and least in mesenteric resistance artery in which the
      acetylcholine-induced, L-NA-resistant relaxation was inhibited by 80 nM-0.4
      microM clotrimazole. These results suggested that there is a regional difference
      in the degree of involvement of NO in acetylcholine-induced relaxation. In
      mesenteric resistance artery, the NO-independent, clotrimazole-sensitive factor,
      possibly hyperpolarizing factor may also contribute to the response to
      acetylcholine at high concentrations.

PMID- 9253952
TI  - Role of nitric oxide in the effects of hypoglycemia on the cerebral circulation
      in awake goats.
AB  - This study was performed to examine the role of nitric oxide in the effects of
      hypoglycemia on the cerebral circulation. Hypoglycemia was induced with insulin
      and its effects on cerebral blood flow (measured with an electromagnetic flow
      transducer placed on the internal maxillary artery) were studied in awake goats
      under control conditions and after administration of the nitric oxide synthesis
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 47 mg/kg). Also,
      cerebrovascular reactivity to vasodilator stimuli was examined during insulin
      induced severe hypoglycemia, before and after L-NAME treatment. In five animals
      under control conditions (glycemia = 90 +/- 7 mg/dl, cerebral blood flow = 64 +/-
      4 ml/min, mean systemic arterial pressure = 102 +/- 4 mmHg, cerebrovascular
      resistance = 1.62 +/- 0.11 mmHg/ml per min and heart rate = 73 +/- 6 beats/min),
      insulin decreased glycemia: when hypoglycemia was moderate (glycemia = 46 +/- 2
      mg/dl) or severe (glycemia = 26 +/- 1 mg/dl) cerebral blood flow increased by 25
      +/- 4% and 47 +/- 6%, and cerebrovascular resistance decreased by 18 +/- 3% and
      34 +/- 4%, respectively. Under basal conditions, L-NAME did not affect glycemia
      but reduced resting cerebral blood flow by 37 +/- 2%, increased mean arterial
      pressure by 33 +/- 2% and decreased heart rate by 28 +/- 3%; after L-NAME, both
      moderate and severe hypoglycemia did not alter significantly resting cerebral
      blood flow and cerebrovascular resistance. In five other goats, L-NAME,
      administered during severe hypoglycemia, abolished the increase in cerebral blood
      flow, and increased cerebrovascular resistance and mean arterial pressure over
      the control (normoglycemic) values. In these animals with severe hypoglycemia,
      acetylcholine (0.01-1 microg), isoproterenol (0.03-3 microg) and diazoxide (0.3-9
      mg), injected into the internal maxillary artery, decreased cerebrovascular
      resistance in a dose-dependent manner, and this decrease was similar before and
      after L-NAME. Therefore, insulin-induced hypoglycemia may produce cerebral
      vasodilatation by releasing nitric oxide and may diminish the capacity of the
      cerebral vasculature to release nitric oxide in response to acetylcholine.

PMID- 9253953
TI  - Effects of adrenomedullin on rat cerebral arterioles.
AB  - The effects of adrenomedullin on isolated rat intracerebral arterioles were
      investigated and compared with those of calcitonin gene-related peptide (CGRP)
      and amylin. Adrenomedullin produced dose-dependent vasodilation (maximum dilation
      27.1 +/- 2.1% at 3 x 10(-7) M, median effective dose (EC50)) 1.6 x 10(-9) M).
      CGRP produced similar vasodilation (19.8 +/- 4.1%) at 10(-7) M with a lower EC50
      of 2.8 x 10(-11) M. Amylin did not cause vasodilation at concentrations up to 10(
      6) M. Adrenomedullin-induced vasodilation was significantly suppressed by CGRP-(8
      37). These data suggest that adrenomedullin is a potent vasodilator for
      arterioles in the cerebral microcirculation that acts through CGRP receptors.

PMID- 9253954
TI  - Arachidonic acid and its metabolites are involved in the expression of morphine
      dependence in guinea-pig isolated ileum.
AB  - The effects of phospholipase A2, cyclooxygenase-1, cyclooxygenase-2 and 5
      lipoxygenase inhibitors were investigated on the naloxone-precipitated withdrawal
      contracture of the acute morphine-dependent guinea-pig ileum in vitro. Mepacrine
      (a phospholipase A2 inhibitor), tolmetin (selective cyclooxygenase-1 inhibitor)
      and meloxicam (selective cyclooxygenase-2 inhibitor) treatment before or after
      morphine was able to both prevent and reverse the naloxone-induced contracture
      after exposure to morphine in a concentration-dependent fashion. Also,
      nordihydroguaiaretic acid (5-lipooxygenase inhibitor) was able to block the
      naloxone-induced contracture following exposure to morphine when injected before
      or after the opioid agonist. The results of the present study suggest that
      arachidonic acid and its metabolites (prostaglandins and leukotrienes) are
      involved in the development of opioid withdrawal.

PMID- 9253955
TI  - Renal vasoconstrictor response to 5-hydroxytryptamine in the in situ autoperfused
      rat kidney: involvement of angiotensin II and the 5-HT2 receptor activation.
AB  - Using a number of agonist and antagonist compounds, we attempted to characterize
      the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT)
      in the in situ autoperfused rat kidney. An intra-arterial (i.a.) bolus injection
      of 5-HT (0.0125 to 0.1 microg/kg) increased renal perfusion pressure in a dose
      dependent way but did not change the systemic blood pressure. The 5-HT2 receptor
      agonist, (1-(3-chlorophenyl) piperazine), m-CPP, caused a local vasoconstrictor
      effect in the autoperfused rat kidney. An intra-arterial injection of 5
      carboxamidotryptamine, 5-CT and 1-(m-chlorophenyl)-biguanide (m-CPBG) did not
      modify the renal perfusion pressure. The vasoconstrictor effect elicited by 5-HT
      and m-CPP was significantly decreased by ritanserin, enalapril and losartan but
      was not modified by prazosin, propranolol or indomethacin pretreatment. Our data
      suggest that the vasoconstrictor serotonergic response induced in the in situ
      autoperfused rat kidney is mediated through angiotensin II activation by a local
      5-HT2 receptor mechanism.

PMID- 9253956
TI  - Compensation of muscarinic bronchial effects of talsaclidine by concomitant
      sympathetic activation in guinea pigs.
AB  - The aim of the present investigation was to determine the reasons why the
      muscarinic receptor agonist talsaclidine (WAL 2014 FU, 1-azabicyclo[2.2.2]
      octane,3-(2-propynyloxy)-, (R)-,(E)-2-butenedioate) is devoid of bronchospastic
      effects in anaesthetized guinea pigs but causes contracture in isolated tracheal
      muscle from this species. Effects on airway resistance were assessed with a
      modified Konzett-Rossler method in guinea pigs anaesthetized with urethane.
      Intravenous injection of 1-64 mg/kg talsaclidine did not cause substantial
      bronchospasm in control animals. After blockade of beta-adrenoceptors, the
      muscarinic receptor agonist induced dose-dependent bronchospasm which could be
      blocked by atropine. In despinalized animals and in animals with spinal
      transection, talsaclidine was bronchospastic but ED50 values were higher and
      maximal effects were smaller than in intact animals after beta-adrenoceptor
      blockade. In adrenalectomized guinea pigs, talsaclidine was nearly as
      bronchospastic as after blockade of beta-adrenoceptors. In contrast, the
      muscarinic ganglion stimulant McN-A-343, 4-(m-chlorophenylcarbamoyloxy)-2-butyn
      trimethyl-ammonium chloride, (2-32 mg/kg i.v.), which has a muscarinic receptor
      profile similar to that of talsaclidine, i.e., full muscarinic agonism and
      highest affinity at muscarinic M1 receptors, partial agonism at muscarinic M3
      receptors, but in contrast to talsaclidine does not penetrate the blood-brain
      barrier, caused dose-dependent bronchospasm in control animals. These results
      indicate that talsaclidine has bronchospastic potential which, however, does not
      become evident in vivo because of functional antagonism via beta-adrenoceptors
      resulting from concomitant activation of the sympathetic nervous system in
      general and the adrenals in particular. It can be concluded that the unique
      profile of action of talsaclidine is due to partial agonism at bronchial
      muscarinic M3 receptors, a prerequisite for susceptibility to functional
      antagonism, and to its ability to penetrate the blood-brain barrier readily and
      to induce sympathetic activation as a result of full agonism at peripheral
      ganglionic and adrenal as well as central muscarinic M1 receptors.

PMID- 9253957
TI  - Inhibition of brain cyclooxygenase-2 activity and the antipyretic action of
      nimesulide.
AB  - The antipyretic action and the mechanism of action of 4-nitro-2
      phenoxymethanesulfonanilide (nimesulide), a new nonsteroidal antiinflammatory
      drug, were investigated in yeast-induced febrile rats. Yeast-injected rats
      developed marked fever and exhibited an approximately 7-fold increase in brain
      levels of prostaglandin E2 and an approximately 2-fold increase in the expression
      of cyclooxygenase-2 mRNA despite an almost unchanged expression of cyclooxygenase
      1 mRNA. Nimesulide produced a dose dependent antipyretic action, which was
      stronger than that of indomethacin and ibuprofen, and decreased dose dependently
      the increased brain prostaglandin E2 levels, whereas it did not influence the
      expression of cyclooxygenase-2 mRNA. It inhibited markedly the enhanced brain
      cyclooxygenase activity, primarily cyclooxygenase-2, in vivo and dose dependently
      increased brain cyclooxygenase activity in vitro. These results suggest that the
      marked antipyretic action of nimesulide is primarily mediated through the
      selective inhibition of the activity of brain cyclooxygenase-2 induced under
      febrile conditions.

PMID- 9253958
TI  - Influence of fatty acid ethanolamides and delta9-tetrahydrocannabinol on cytokine
      and arachidonate release by mononuclear cells.
AB  - The effects of arachidonic acid ethanolamide (anandamide), palmitoylethanolamide
      and delta9-tetrahydrocannabinol on the production of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-4, interleukin-6, interleukin-8, interleukin-10,
      interferon-gamma, p55 and p75 TNF-alpha soluble receptors by stimulated human
      peripheral blood mononuclear cells as well as [3H]arachidonic acid release by non
      stimulated and N-formyl-Met-Leu-Phe (fMLP)-stimulated human monocytes were
      investigated. Anandamide was shown to diminish interleukin-6 and interleukin-8
      production at low nanomolar concentrations (3-30 nM) but inhibited the production
      of TNF-alpha, interferon-gamma, interleukin-4 and p75 TNF-alpha soluble receptors
      at higher concentrations (0.3-3 microM). Palmitoylethanolamide inhibited
      interleukin-4, interleukin-6, interleukin-8 synthesis and the production of p75
      TNF-alpha soluble receptors at concentrations similar to those of anandamide but
      failed to influence TNF-alpha and interferon-gamma production. The effect of both
      compounds on interleukin-6 and interleukin-8 production disappeared with an
      increase in the concentration used. Neither anandamide nor palmitoylethanolamide
      influenced interleukin-10 synthesis. delta9-Tetrahydrocannabinol exerted a
      biphasic action on pro-inflammatory cytokine production. TNF-alpha, interleukin-6
      and interleukin-8 synthesis was maximally inhibited by 3 nM delta9
      tetrahydrocannabinol but stimulated by 3 microM delta9-tetrahydrocannabinol, as
      was interleukin-8 and interferon-gamma synthesis. The level of interleukin-4,
      interleukin-10 and p75 TNF-alpha soluble receptors was diminished by 3 microM
      delta9-tetrahydrocannabinol. [3H]Arachidonate release was stimulated only by high
      delta9-tetrahydrocannabinol and anandamide concentrations (30 microM). These
      results suggest that the inhibitory properties of anandamide,
      palmitoylethanolamide and delta9-tetrahydrocannabinol are determined by the
      activation of the peripheral-type cannabinoid receptors, and that various
      endogenous fatty acid ethanolamides may participate in the regulation of the
      immune response.

PMID- 9253960
TI  - Effects of phorbol ester on carbachol-induced contraction in bovine ciliary
      muscle: possible involvement of protein kinase C.
AB  - The aim of the research was to characterize muscarinic receptors of bovine
      ciliary muscle and to investigate the desensitization process. The role of
      protein kinase C was analyzed. The results show that muscarinic receptors of
      bovine ciliary muscle have the pharmacological characteristics of the M3 subtype.
      Acute exposure to phorbol esters (1 microM phorbol 12,13-dibutyrate, PDB, or 0.1
      microM phorbol 12-myristate 13-acetate, PMA, for 15 and 5 min, respectively)
      resulted in antagonism of muscarinic receptor-mediated contraction. Long-term
      pretreatment (18 h) with PMA to down-regulate protein kinase C resulted in
      potentiation of carbachol-induced contraction, reduction of agonist-induced
      desensitization and loss of phorbol ester-induced desensitization. Staurosporine
      (3 microM) and H7 [1-(5-isoquinolinesulfonyl)-2-methyl-piperazine] (1 microM),
      protein kinase C inhibitors, produced a significant potentiation of the
      contractile effect of carbachol, reduced the desensitization produced by repeated
      addition of carbachol and suppressed that induced by phorbol esters. In vitro
      incubation with carbachol, PDB or PMA did not cause any modification of the
      binding of labeled [3H]quinuclidinyl benzilate. In vitro incubation with PDB and
      PMA produced, as expected, a significant translocation of protein kinase C from
      the cytosol to the membrane. The incubation of the ciliary muscle with carbachol,
      using the protocol of exposure that induced maximal desensitization of
      contractile responses, produced a significant redistribution of the enzyme from
      the cytosol to the membrane. These findings suggest that agonist-induced
      modulation of functional cholinergic sensitivity in ciliary muscle is correlated,
      at least partially, to the translocation of protein kinase C from the cytosol to
      the membrane. The desensitization by phorbol esters is completely due to protein
      kinase C activation; during the desensitization process, direct modification of
      the density and affinity of muscarinic receptors is not involved.

PMID- 9253959
TI  - Persistence of effects of nitric oxide synthase inhibitors: comparisons on blood
      flow and plasma exudation in guinea pig skin.
AB  - Plasma protein extravasation has been measured in guinea pig skin using 125I
      albumin and blood flow using 133Xenon (133Xe) clearance. The nitric oxide (NO)
      synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-monomethyl
      L-arginine (l-NMMA) and N(G)-nitro-L-arginine (L-NOArg) and the alpha
      adrenoceptor agonist, phenylephrine, inhibited bradykinin induced plasma protein
      extravasation when co-injected with the peptide. The inhibitory effects of L-NAME
      and L-NOArg lasted for up to 8 and 4 h, respectively, whereas phenylephrine and L
      NMMA had no persistent inhibitory effects. When co-injected with 133Xe, L-NAME, L
      NMMA, L-NOArg and phenylephrine, but not D-NAME, produced significant reductions
      in skin blood flow. When injected prior to 133Xe, L-NAME and L-NOArg, but not
      phenylephrine or L-NMMA, significantly reduced flow. The effect of L-NAME on flow
      was not significant at 8 h. Thus, although the inhibitory effects of the NO
      synthase inhibitors on mediator induced plasma protein extravasation show
      correlations with their effects on blood flow, the persistent effect of L-NAME on
      exudation appears to extend beyond its effect on flow.

PMID- 9253961
TI  - Angiotensin receptor subtypes in the uterine artery during ovine pregnancy.
AB  - This study was undertaken to determine if changes in receptor density or affinity
      could account for the reduced vascular sensitivity to angiotensin II seen during
      pregnancy. Angiotensin receptor subtypes in the uterine arteries of non-pregnant,
      pregnant and postpartum ewes were investigated using saturation and competition
      receptor binding techniques with the specific receptor antagonists, losartan (DuP
      753) and PD-123319 (S)1-[[4-(dimethylamino)-3-methylphenyl]-methyl]-5
      (diphenylacetyl )-4,5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid,
      ditrifluoroacetate, monohydrate). Receptor density and affinity of total
      angiotensin receptors, as well as the angiotensin AT1 and AT2 receptor subtypes
      in uterine arteries were compared with those in the mesenteric artery and aorta.
      The uterine artery contains both AT1 and AT2 receptor subtypes, whereas the
      mesenteric artery and aorta contain primarily the AT1 receptor subtype. In
      uterine arteries from pregnant sheep, angiotensin receptor density was increased
      because AT2 receptors were increased. AT1 receptor density was not altered. This
      change was not seen in the aorta. In the uterine artery, receptor affinity for
      [Sar1,Ile8]angiotensin II decreased in mid-gestation (IC50 7.7 +/- 1.2 x 10(-9)
      M) compared with non-pregnant ewes (IC50 3.0 +/- 0.6 x 10(-9) M, P = 0.006), and
      there was decreased affinity of angiotensin AT1 receptors for losartan during
      pregnancy (IC50 2.8 +/- 1.0 x 10(-4) M) compared with non-pregnant ewes (IC50 2.2
      +/- 1.3 x 10(-6) M, P = 0.025). Our results show changes in the density and
      affinity of the angiotensin receptor subtypes in the uterine artery which could
      explain its reduced responsiveness to circulating angiotensin II during
      pregnancy.

PMID- 9253962
TI  - Effects of constant and flickering light on retinal metabolism in rabbits.
AB  - PURPOSE: To characterize the glucose metabolism in the rabbit retina. METHODS: An
      artery and a vortex vein were cannulated. Arteriovenous differences in oxygen,
      lactate and glucose concentrations, and blood flow were determined during either
      1) darkness and light, or 2) light and 4 Hz flickering light. RESULTS: In
      darkness, oxygen consumption, glucose consumption, and lactate formation were
      0.122 +/- 0.014, 0.204 +/- 0.015 and 0.160 +/- 0.023 micromol/min (mean +/- SE),
      respectively. Constant light reduced oxygen consumption insignificantly, and had
      no effect on glucose consumption. Hyperoxia did not affect the lactate formation.
      Flickering light increased the glucose consumption and lactate formation by 15
      20%. CONCLUSIONS: In rabbits, 10% of the glucose consumed is oxidized, 40-50% is
      metabolized to lactate and the rest is used for other purposes. The glycolysis is
      primarily aerobic. Flickering light increases the glucose metabolism, constant
      light having little effect.

PMID- 9253963
TI  - The role of nitric oxide in hyperaemic response to flicker in the retina and
      optic nerve in cats.
AB  - PURPOSE: To elucidate the role of nitric oxide (NO) in the eye and the flicker
      induced vascular response. METHODS: The blood flow in the retina and different
      parts of the optic nerve was compared in cats treated with the NO-synthase
      blocker, N(G)-nitro-L-arginine methyl ester and in control animals. In both
      groups, one of the eyes was dark-adapted, the other was subjected to 8 Hz
      flickering light. The regional blood flow was measured with the microsphere
      method. RESULTS: In control animals, flickering light increased blood flow in the
      retina and optic nerve head by 39% and 256%, respectively. Pretreatment with N(G)
      nitro-L-arginine methyl ester prevented this increase in retinal blood flow and
      markedly reduced the blood flow in the optic nerve heads. CONCLUSION: NO release
      may mediate much of the vasodilating effect of flicker in cats, and play a role
      in maintaining normal vascular tone in the optic nerve head.

PMID- 9253965
TI  - Glial cell involvement in vascular occlusion of diabetic retinopathy.
AB  - Twenty areas of retinal vascular occlusion from ten eyes of 6 diabetic patients
      were studied by immunohistochemistry to type IV collagen (basement membranes),
      von Willebrand factor (endothelial cells), and to glial fibrillary acid protein
      (glial cells) on serial sections. In all studied lesions immunoreactivity to type
      IV collagen and von Willebrand factor was confined to the retinal vascular walls
      whereas the material accumulated to occlude the vascular lumens centrally
      displayed immunoreactivity to glial fibrillary acid protein. All arterioles
      observed in the lesions were occluded. These arterioles had retained their
      circular shape, and the intravascular glial protein immunoreactivity communicated
      with the extravascular glial tissue through localised breaks in the vascular
      wall. The intravascular immunoreactivity was found to continue inside the
      arteriole along its successive diminishing to reach the capillary level. The
      venules were only occluded in less than half of the studied lesions. These
      venules were collapsed to assume a bean-like shape, and sequences with total
      obliteration of the vascular lumen alternated with sequences where a residual
      space corresponding to the former lumen displayed immunoreactivity to glial
      protein. The paper suggests that glial cell invasion, but not endothelial cells
      or basement membrane thickening, occludes the vascular lumen in areas of retinal
      non-perfusion secondary to diabetic retinopathy.

PMID- 9253964
TI  - Effects of dorzolamide hydrochloride 2% on the retinal circulation.
AB  - PURPOSE: To study the effect of a single dose of topical dorzolamide
      hydrochloride 2%, a carbonic anhydrase inhibitor, on the retinal circulation of
      normal subjects. METHODS: Measurements of the effect of dorzolamide hydrochloride
      were performed in 20 normal subjects using bidirectional laser Doppler
      velocimetry and monochromatic fundus photography. In a double-masked randomized
      design, one eye received one drop of dorzolamide hydrochloride 2 % and the other
      eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity and
      volumetric blood flow rate were measured in a main temporal vein of each eye
      before the drops, and then, 2 h later. RESULTS: Following treatment, intraocular
      pressure decreased by 12% in the dorzolamide-treated eye (p = 0.0004, paired
      Student's t-test) and by 4% in the placebo-treated eye, p = 0.04). No significant
      changes in venous diameter, maximum erythrocyte velocity, and volumetric blood
      flow rate were observed in the dorzolamide-treated eyes (0.6%, 2.6% and 1.4%,
      respectively) or the placebo-treated eyes (1%, 3.7% and 1.6%, respectively).
      CONCLUSIONS: A single drop of dorzolamide hydrochloride does not cause any
      significant change in any of the hemodynamic parameters measured. With the
      variability of our measurements, we have about 89% power to detect average 10%
      change in volumetric blood flow rate if significance testing is performed at p =
      0.05 level.

PMID- 9253966
TI  - Retinal examination intervals in diabetic patients on diet treatment only.
AB  - PURPOSE: The aim of the present study was to examine whether type 2 diabetic
      patients with good metabolic control achieved on diet treatment only, developed
      sight-threatening retinopathy during a four-year follow-up period. METHODS: A
      retrospective four-year follow-up study was carried out including all diabetic
      patients on diet treatment only, registered at the out-patient clinic at the
      Department of Medicine and referred for fundus photography to the Department of
      Ophthalmology in 1989 as well as all patients referred from primary care units
      for fundus photography during 1988 and 1989. One hundred and seventeen diabetic
      patients treated with diet only were examined with fundus photography after
      remittance, and after two and four years. RESULTS: Age at diabetes diagnosis was
      58.8 +/- 13.8 years (mean +/- SD), age at baseline was 61.5 +/- 13.6 years, and
      diabetes duration was 2.7 +/- 3.1 years. During the four-year follow-up period,
      48 of the patients (41%) remained on diet treatment only whereas diabetes
      treatment was changed in 66 (56%), from diet to oral agents only in 57 (49%), and
      from diet to insulin alone or in combination with oral agents in 9 (8%) of the
      patients. One hundred and six patients (91%) did not have any retinopathy at
      baseline and 11 patients (9%) had minimal background retinopathy. At follow-up,
      there were no signs of retinopathy in 93 patients (79%), 22 (19%) had minimal
      background retinopathy, and two had developed moderate background retinopathy.
      Out of those patients who were still on diet at follow-up, five (10%) had
      developed minimal background retinopathy. Mean blood glucose and HbA1c levels,
      registered every year during the observation period, were higher at most time
      points in patients who received oral agents or insulin treatment compared to
      those who were treated with diet only during the entire observation period. No
      differences were observed between patients who received oral agents and those who
      received insulin alone or in combination with oral agents. CONCLUSION: It is
      suggested, that if the initial retinal examination reveals no or minimal diabetic
      retinopathy at the time of diagnosis of type 2 diabetes mellitus, the second
      examination can be postponed at least 4 years in patients with good metabolic
      control on diet treatment only.

PMID- 9253967
TI  - Active prevention in diabetic eye disease. A 4-year follow-up.
AB  - Ten years after the foundation of a national diabetic eye screening program in
      1980, we have established a low prevalence of blindness and partial sight in type
      1 and type 2 diabetics in Iceland. We ask whether the screening program is also
      associated with a low incidence of blindness in diabetics. We now report the
      results of a prospective study on the 4-year incidence of diabetic retinopathy
      and visual impairment in type 1 diabetics with age at onset less than 30 years.
      Out of 205 patients participating at baseline, 175 patients (85.4%) participated
      over the full 4-year period. Patients were examined annually and received laser
      treatment according to Diabetic- and Early Treatment Diabetic Retinopathy Study
      criteria. The 4-year incidence of any retinopathy was 38.1%, of proliferative
      retinopathy 6.6%, and of macular edema 3.4%. Out of 174 patients, 7.4% showed
      improvement in visual acuity of 2 Snellen lines while 2.5% experienced worsening
      of visual acuity of 2 Snellen lines during the 4-year period. No diabetic
      suffered more than 2 lines deterioration of vision and none became legally blind.
      The incidence of retinopathy in Icelandic type 1 diabetics participating in our
      annual eye screening program is low and the visual acuity stable. Our results
      suggest that visual impairment in diabetics can be prevented with active regular
      screening and standard laser therapy.

PMID- 9253968
TI  - Pseudo-exfoliation and mortality.
AB  - The hypothesis that ocular pseudo-exfoliation syndrome is part of a generalized
      disorder has been tested by suggesting that subjects having this syndrome would
      have increased mortality. However, no association was found between presence of
      ocular pseudo-exfoliation syndrome and mortality.

PMID- 9253969
TI  - Hyaluronan in the exfoliation syndrome.
AB  - PURPOSE: To histochemically analyze if the glycoseaminoglycan component of
      pseudoexfoliation material consists of hyaluronan. METHODS: The hyaluronan
      binding region of cartilage proteoglycans was utilized in a staining specific for
      hyaluronan. The technique has been described and employed previously. Human donor
      eyes with and without the presence of visible pseudoexfoliations were analyzed.
      RESULTS: Hyaluronan was found to coat the fibrillar exfoliation material on the
      lens, the zonules, the iris epithelium and the ciliary body. It was also found on
      a capsular bag following cataract surgery. CONCLUSION: In the anterior chamber
      hyaluronan constitutes one part of the exfoliation material. Abnormal findings of
      hyaluronan could be found in the cornea.

PMID- 9253970
TI  - Indocyanine green angiography in angioid streaks.
AB  - PURPOSE: To define the indocyanine green angiographic aspects of angioid streaks,
      peau d'orange and choroidal new vessels. METHODS: Fifty-seven consecutive
      patients (112 eyes) with angioid streaks were evaluated by fluorescein
      angiography and indocyanine green angiography. RESULTS: Indocyanine green
      angiography showed angioid streaks in all eyes. We identified three different
      indocyanine green patterns of streaks (four groups): fluorescent (63%),
      hypofluorescent (8%), 'track-like' (19%) and mixed (10%). Angioid streaks were
      visualized better by indocyanine green angiography and red-free retinography than
      fluorescein angiography. Peau d'orange was seen better and found to be more
      widespread by indocyanine green angiography. Fluorescein angiography visualized
      choroidal neovascularization better, except for occult forms. CONCLUSIONS: Our
      findings show that angioid streaks have different indocyanine green angiography
      patterns. Considering that the hypofluorescent pattern was significantly observed
      in younger patients, indocyanine green angiography aspects might be correlated
      with different stages of the disease.

PMID- 9253971
TI  - Five years' experience with the Grating disc. A simplified method of evaluating
      vision in young children.
AB  - The Grating Disc (GD) is a simplified visual test designed for children 18 months
      to 4 approximately 5 years. Two hundred pediatric patients (103 males, 97
      females; aged 5 months to > 6 years) participated in this study to determined how
      the GD visual acuity (VA) correlates with the Preferential Looking (PL) VA. Forty
      six percent of the patients had varying degrees of retinopathy of prematurity.
      The PL acuity was determined using the up-and-down staircase procedure. To
      measure GD acuity, six GDs with vertical gratings equivalent to acuities of
      20/1920 to 20/60 were used. The examiner presented one GD simultaneously with the
      homogeneous disc from 57 cm. The VA was determined by the finest GD that the
      child could differentiate from the homogeneous disc. The overall correlation
      between the PL and the GD acuities was very high (R2 = 0.861). One hundred twenty
      eight patients (64.0%) had an acuity agreement within 0.5 octave and 178 (89.0%)
      patients were within 1.0 octave. When the PL acuity was > or = 20/100, the GD and
      PL acuities showed good agreement. When the PL acuity was poorer, the GD acuity
      was poorer than the PL acuity. Although the GD acuity tended to be lower than the
      PL acuity in severely visually impaired patients, the GD acuity agreed with the
      PL in most visual assessments of young children. GD testing could be a useful
      alternative when sophisticated assessment systems such as the PL are unavailable.

PMID- 9253972
TI  - Intraocular lens thickness and ocular growth in newborn rabbits.
AB  - PURPOSE: To examine ocular growth in newborn rabbits with a thick or a thin
      silicone intraocular lens implanted. METHODS: Bilateral lensectomy was performed
      in twelve 23-day-old rabbits. All eyes were implanted with a silicone intraocular
      lens (IOL) with polypropylene haptics (Allergan Medical Optics SI 26 NB). In each
      rabbit, one eye was selected at random and a +12 diopter IOL with a centre
      thickness of 1.10 mm was implanted in the capsular bag. In the other eye a +24
      diopter IOL with a centre thickness of 1.83 mm was implanted. Axial length,
      corneal diameter, corneal thickness and intraocular pressure were measured in all
      eyes preoperatively, and then 1, 2 and 3 months after surgery. The wet mass of
      the after-cataract was measured 3 months after surgery. RESULTS: Both the axial
      length and the corneal diameter were significantly increased in eyes implanted
      with the thicker silicone IOL. No significant difference in corneal thickness or
      intraocular pressure was found between the eyes. No correlation was found between
      the IOL-thickness and the wet mass of the after-cataract. CONCLUSION: The results
      suggest that in the young rabbit eye the thickness of an implanted IOL influences
      eye growth.

PMID- 9253973
TI  - Visual development in healthy eyes from 24 months to four years of age.
AB  - The study is of visual development from 24 months to 4 years of age. The O-test
      was used in children from 24 to 27 months of age; and the Kolt-test from 28
      months to 4 years. One measurement was performed in both eyes of 89 normal
      children aged from 24 months to 4 years. The mean visual acuity was 0.48 at 24 to
      29 months; 0.55 at 30 to 35 months; 0.67 at 36 to 41 months; 0.77 at 3 1/2 to 4
      years of age.

PMID- 9253974
TI  - How are macular changes reflected in pattern visually evoked cortical potentials?
AB  - To investigate the macular contribution to the amplitude and latency of pattern
      visual evoked cortical potentials (PVECPs), we recorded PVECPs in patients with
      unilateral macular disease (retinal diseases involving the macular region) and
      optic neuritis. We selected patients with visual acuities better than 0.3, which
      is thought to be the minimum acuity to provide clearly discernible responses. The
      visual stimulus was a checkerboard. We varied the check size in 4 steps as 7, 14,
      28, and 56 min of arc, and the contrast was 20% or 80%. The amplitude of the
      sinusoidal wave of steady-state VECPs (12 Hz) and the P100 component of a
      transient VECP (3 Hz) were measured. Significant attenuation and delay of PVECPs
      in the affected eye were found in the macular disease group. Macular disease may
      cause an increase of VECP latency. However, VECP seemed to be a more sensitive
      test of optic nerve disease than of macular disease, when patients had similar
      visual acuities.

PMID- 9253975
TI  - Keratoconjunctivitis sicca and primary Sjogren's syndrome in a Danish population
      aged 30-60 years.
AB  - PURPOSE: To investigate the presence of keratoconjunctivitis sicca and primary
      Sjogren's syndrome a sample of 504 persons aged 30-60 years from Copenhagen was
      studied. METHODS: The presence of keratoconjunctivitis sicca and primary
      Sjogren's syndrome was estimated according to both the Copenhagen set of criteria
      and the preliminary European criteria. RESULTS: Symptoms of dry eye and oral
      dryness were very common and with no significant correlation to age or sex.
      Keratoconjuncitivis sicca was most frequent in persons aged 50-59 years and was
      equally common in men and women. Primary Sjogren's syndrome could only be
      diagnosed in one person according to the Copenhagen criteria (cut-off the
      Schirmer-1 test < or = 5 mm/5 min), and in three persons according to the
      preliminary European criteria. CONCLUSION: The frequency of keratoconjunctivitis
      sicca in persons aged 30-60 years in Copenhagen may be estimated to be 11%
      according to the Copenhagen criteria and 8% according to the preliminary European
      criteria. The frequency of primary Sjogren's syndrome in persons aged 30-60 years
      in Copenhagen may be estimated to be between 0.2% and 0.8% according to the
      Copenhagen criteria and between 0.6% and 2.1% according to the preliminary
      European criteria.

PMID- 9253977
TI  - Quantitative study of the effect of dacryocystorhinostomy on lacrimal drainage.
AB  - Using scintigraphy, we have studied the lacrimal drainage from the conjunctival
      sac of normal subjects and patients who have undergone dacryocystorhinostomy. A
      mathematical model of drainage was constructed that accurately described the
      complete activity curves for both groups. The initial rate of drainage was shown
      to be a relevant parameter to characterize drainage, and it was found to be
      different from normals to patients, indicating that the lacrimal pump mechanism
      is affected by dacryocystorhinostomy.

PMID- 9253976
TI  - The importance of plasma polymorphonuclear (PMN) elastase determination in
      patients with uveitis.
AB  - PURPOSE: Polymorphonuclear elastase is used as an important marker for
      inflammatory disease. We wanted to show whether polymorphonuclear elastase could
      be a marker in uveitis. METHODS: Twenty-two patients with uveitis and 30 healthy
      control subjects were included in the study. Polymorphonuclear elastase levels
      were determined by immunoactivation method before and after periods of
      corticosteroid and/or cyclosporin treatments. RESULTS: The levels were high in
      all of the patients before treatment; the levels reached normal range with
      treatment. In some cases, however, uveitis could not be suppressed in spite of
      treatment; these patients had high polymorphonuclear elastase levels. CONCLUSION:
      It was concluded that determination of polymorphonuclear elastase level may be
      used for monitoring of uveitis.

PMID- 9253978
TI  - A national glaucoma care program.

PMID- 9253979
TI  - Phaco-emulsification of cataract in eyes with glaucoma.
AB  - This study was conducted to determine how phaco-emulsification and intraocular
      lens (IOL) implantation influenced intraocular pressure (IOP) in eyes with
      glaucoma, and glaucoma medication requirements postoperatively. A retrospective
      clinical analysis was undertaken of 226 eyes of 182 glaucoma patients who had
      undergone phacoemulsification and IOL implantation. IOP on the first day after
      operation increased from a preoperative mean of 17.1 mmHg (SD +/- 3.9 mmHg) to a
      mean of 20.7 mmHg (SD +/- 9.0 mmHg). One week after operation the average IOP was
      17.4 mmHg (SD +/- 5.5 mmHg). One year after operation the average IOP had
      declined to 15.3 mmHg (SD +/- 3.1 mmHg). One year after operation 34% of the
      patients did not need glaucoma medication. If glaucoma is fairly well controlled
      (mean IOP preoperative 17.1 mmHg) phaco-emulsification alone can result in
      satisfactory IOP control in eyes with capsular and primary open-angle glaucoma.

PMID- 9253981
TI  - Incidence of retinopathy of prematurity (ROP) in the western part of Norway. A
      population-based retrospective study.
AB  - We have investigated the incidence of retinopathy of prematurity (ROP) among
      premature infants with birth weight less than 1500 g in two Norwegian counties
      during the years 1989-1993. Two hundred and seven out of 244 such infants (84.8%)
      were examined at the neonatal intensive care unit; 66 of those examined (31.9%)
      had a birth weight below 1000 g. ROP was found in 21 patients (10.1%), and stage
      3 disease was present in 7 (3.4%). No patient had more advanced ROP than stage 3.
      Assuming that no cases of stage 3 ROP were missed among the total of 244
      children, the incidence of stage 3 disease was 2.9%. The frequency of ROP in this
      study is compared to that of other population-based studies in the Nordic
      countries, and incidence differences are discussed.

PMID- 9253980
TI  - Relationships of orbital computed tomographic findings and activity scores to the
      prognosis of corticosteroid therapy in patients with Graves' ophthalmopathy.
AB  - To elucidate the relationships of orbital computed tomographic findings and
      activity scores to the prognosis of corticosteroid therapy in patients with
      Graves' ophthalmopathy, 22 cases were treated with corticosteroid. Orbital
      computed tomographic was performed before treatment and the maximal muscle areas
      of rectus muscle bellies were calculated from the coronal images. Activity scores
      were calculated according to the recommendations of an international ad hoc
      committee. The clinical severity of the eye disease was based on the NOSPECS
      classification. Observation of the effectiveness of treatment at 6 months allowed
      patients to be classified into good responders or poor responders. Twelve of 22
      patients (54.5%) belonged to the good responders. The total muscle areas were
      less in good responders. Although the total muscle areas were significantly
      correlated with the activity scores, no difference in the activity scores was
      noted between these two groups. We concluded that although activity score seems
      to be a predictor of initial responsiveness to anti-inflammatory drugs, the
      maximal muscle area is a prognostic factor of corticosteroid therapy in patients
      with Graves' ophthalmopathy.

PMID- 9253982
TI  - Bilateral clinical anophthalmos.
AB  - We report on the risk factors, associations and outcome of 5 children with
      bilateral clinical anophthalmos. Our study showed no gestational, environmental
      or hereditary association but confirmed strong association with multiple systemic
      abnormalities.

PMID- 9253983
TI  - The use of capsaicin in herpes zoster ophthalmicus neuralgia.
AB  - The treatment of neuralgia which occurs during and following herpes zoster
      ophthalmicus is often unsatisfactory. Capsaicin (trans-8-methyl-N-vanillyl-6
      nonenamide) is a drug which depletes substance P and may be effective in
      inhibiting pain. We utilized topical capsaicin to the affected dermatome five
      times daily for 4 weeks in 6 patients with acute and post herpetic neuralgia. In
      four cases pain was markedly relieved and narcotic medications were either
      discontinued or significantly reduced. In two cases, pain was not reduced. Four
      patients had side effects including burning sensation at the site of the drug
      administration (4 cases), dermatitis as a result of overuse of the drug (2 cases)
      and hyperesthesia (1 case). Our results suggest that capsaicin may be a useful
      therapy for the alleviation of pain in some individuals with herpes zoster
      ophthalmicus. However, controlled studies are needed to establish these results.

PMID- 9253984
TI  - Bilateral anterior uveitis and retinal haemorrhages after administration of
      trimethoprim.
AB  - In this case report we present a female patient with recurrent urinary infection
      treated with trimethoprim/sulfamethoxazole, trimethoprim alone and ciprofloxacin.
      She developed adverse systemic symptoms and bilateral anterior uveitis following
      administration of the former two drugs, and in addition retinal haemorrhages
      after the use of trimethoprim. Uveitis and retinal haemorrhages are rare side
      effects of trimethoprim/sulfamethoxazole. To our best knowledge they have not
      been described as a side effect of trimethoprim alone.

PMID- 9253985
TI  - Cilioretinal artery occlusion following scleral reinforcement surgery.
AB  - A 12-year-old high myope girl presented with a cilioretinal artery occlusion in
      her left eye. Three years previously, she had undergone posterior scleral support
      surgery to prevent the progression of her myopia. The general medical workup of
      the patient did not reveal any causative factor for retinal artery occlusion. A
      possible relation between the cilioretinal artery obstruction and the previous
      scleral reinforcement surgery is postulated based on two proposed mechanisms.

PMID- 9253986
TI  - Wolfring dacryops and needling.
AB  - Cysts of the accessory lacrimal gland of Wolfring are uncommon in Europe; they
      are commoner in areas where trachoma is endemic and usually occur in eyes with
      some evidence of past trachomatous scarring (Bullock et al. 1986). The
      recommended mode of management is surgical, using an operating microscope, with
      an incision through the conjunctiva. Simple aspiration is inappropriate since the
      cyst refills. We describe a case of dacryops of the glands of Wolfring in a
      Caucasian male with no evidence of previous trachoma. This was managed with
      simple needling of the cyst. There was no recurrence of the cyst at 2 years
      follow-up.

PMID- 9253987
TI  - Choroidal neovascularization complicating epiretinal membrane removal.
AB  - PURPOSE: Surgical removal of epiretinal membranes generally leads to anatomic and
      functional improvement. Main complications include cataract, retinal breaks and
      detachment. We describe the onset of a juxtafoveal choroidal neovascularization 2
      years after surgery of an epiretinal membrane. METHODS: The neovascular membrane
      was treated by argon laser photocoagulation. RESULTS: Complete obliteration of
      the neovascularization was obtained resulting in functional improvement.
      CONCLUSIONS: Although rare, choroidal neovascularization as a complication of
      epiretinal membrane surgery must be suspected in case of poor visual outcome or
      relapse of symptoms.

PMID- 9253988
TI  - CHARGE association with congenital glaucoma due to maldevelopment of the anterior
      chamber angle.
AB  - PURPOSE: We examined the clinicopathologic features of a male infant with the
      CHARGE association and bilateral congenital glaucoma. METHODS: Trabeculectomy
      specimens were obtained from the anterior chamber angle and examined by light and
      electron microscopy. RESULTS: Histopathologic examination of the trabeculectomy
      specimens showed immature development of the trabecular meshwork that was covered
      by the ciliary muscles. There were few intertrabecular spaces because the
      meshwork was almost completely filled with cells and extracellular substances.
      Deposition of a granular and/or homogeneous substance was observed in the
      subendothelial area of Schlemm's canal. CONCLUSIONS: Our patient exhibited
      features typical of the CHARGE association, but also had congenital glaucoma. We
      hypothesize that these clinical findings are all mediated by a neurocristopathic
      mechanism. Our findings suggest that the CHARGE association may predispose to
      anterior chamber angle maldevelopment, which can lead to congenital glaucoma.

PMID- 9253989
TI  - Autosomal recessive nanophthalmos.
AB  - Nanophthalmos is a rare congenital ocular malformation which is generally
      recognized at middle age when serious complications have already developed. In
      this report 7 early diagnosed nanophthalmic cases are presented and diagnostic
      criteria, complications, inheritance and various modalities of treatment are
      discussed.

PMID- 9253990
TI  - The long-term follow-up of a highly myopic patient with a macular vortex vein.
AB  - We followed a highly myopic patient with a macular vortex vein for 11 years. His
      refraction was -12D OU at age 10 years when the vein was first observed
      ophthalmoscopically in the left eye. Eleven years later, his myopia had
      progressed (4 diopters OD; 8 diopters OS), and the axial lengths were elongated
      (+1.8 mm OD; +2.7 mm OS). The macular vortex vein was dilated and tortuous.
      Indocyanine green angiography revealed the outflow route of this vein in the
      posterior pole, where both nasal and temporal posterior choroidal venous blood
      collected. Computed tomography showed that the vein left the eyeball directly and
      coursed along the optic nerve 5 mm posterior to the optic disc. A major
      collecting channel of posterior choroid outflow in some highly myopic eyes, a
      macular vortex vein may be formed at a relatively early age, and continue to
      enlarge, with elongation of axial length and progression of myopia.

PMID- 9253991
TI  - Enlargement of extraocular muscles during treatment with amiodarone.
AB  - A case of extraocular muscle enlargement diagnosed 2 months after the start of
      treatment with amiodarone is presented. The orbital CT scan was typical of
      endocrine ophthalmopathy. The patient had no history of hyperthyroidism and
      during a follow-up period of 2 years no laboratory evidence of irregularities in
      the thyroid hormone metabolism was discovered.

PMID- 9253992
TI  - Conjunctival keratoacanthoma.
AB  - Keratoacanthoma is a rapidly growing skin neoplasia that may stabilize or regress
      spontaneously. We describe here a case of conjunctival keratoacanthoma and
      comment about the clinical signs and symptoms and pathological findings.

PMID- 9253993
TI  - The eye and its diseases in Ancient Egypt.
AB  - Based on a study of mummies, skeletons, burial rites, medical instruments,
      medicaments, literature and objets d'art from Ancient Egypt before the
      Hellenistic Period, the understanding of the eye, its diseases and their
      treatment at that time is described. Magic spells, religious rites and medical
      treatments, especially with eye ointments, were probably used often complementary
      to one another. We must be very cautious about our conclusions in regard to the
      effectiveness of the treatments. Eye diseases have been depicted only
      exceptionally in Egyptian art, except for blindness and 'symbolic blindness'.

PMID- 9253994
TI  - Surgery and chronic uveitis.

PMID- 9253995
TI  - Fast spin-echo (FSE) and gradient- and spin-echo (GRASE) in fast MRI of the
      pelvis.
AB  - In this prospective study two different T2-weighted fast spin-echo (FSE)
      sequences and a gradient- and spin-echo (GRASE) sequence were compared in 20
      consecutive patients undergoing clinical pelvic MR examinations. A GRASE and two
      FSE sequences were applied, whereby the FSE sequences differed from each other by
      altered echo spacings (15.0 and 22.5 ms) and T2 contrast. Quantitative image
      analysis included ROI evaluation of different S/N and C/N values. Visual image
      analysis was performed by two independent readers using a standardized score
      sheet for anatomic and pathologic findings. Overall image quality was
      significantly better in both FSE sequences. GRASE and FSE22.5 were superior in
      delineation of most of anatomic and pathologic structures due to intermediate to
      hypointense contrast behavior of pelvic fat compared to FSE15.0 in which fat was
      bright. Therefore, FSE15.0 was optimal for low intensity lesions. Short
      acquisition times of FSE and GRASE sequences allow application of two different
      techniques-fat hypointense respectively bright-for excellent lesion
      visualisation. This study demonstrates the usefulness of contrast manipulation in
      fast T2-weighted MRI techniques without special techniques, such as fat
      saturation.

PMID- 9253996
TI  - MR imaging of thoracic neurilemmomas.
AB  - Magnetic resonance (MR) imaging features of 15 thoracic neurilemmomas were
      analyzed. Morphologically, five tumor patterns could be identified on MR imaging
      including: inhomogeneous masses (n = 8), thick-walled multiloculated masses (n =
      2), thick-walled central cystic masses (n = 2), homogeneous cystic masses (n = 2)
      and a target pattern mass (n = 1). The signal characterization of thoracic
      neurilemmomas was variable, usually brighter on T2-weighted images, hyper- to
      hypo-intense on T1-weighted images and always enhancing. Histopathologically, the
      inhomogeneous masses were characterized by irregular distribution of
      hypercellular Antoni A and hypocellular Antoni B tissues with variable degrees of
      cystic, hemorrhagic, myxoid and hyaline degenerative changes. Enlargement of the
      cystic areas led to the development of thick-walled multiloculated masses while
      confluence of these cystic areas produced a central cystic pattern. Extensive
      myxoid or hyaline degeneration yielded homogeneous cystic tumors. Peripheral
      fibrinous changes and central Antoni B stroma contributed to a target pattern.
      Appreciation of the protean MR manifestations and understanding of the underlying
      histopathological changes of thoracic neurilemmomas are helpful in the diagnosis
      of this tumor.

PMID- 9253997
TI  - Gd-enhanced MR imaging of brain metastases: contrast as a function of dose and
      lesion size.
AB  - MR imaging contrast of brain metastases after cumulative doses of gadolinium
      chelate is quantitated and compared in order to assess the clinical utility of
      high dosage. T1-weighted spin-echo MR images of 39 patients with metastatic brain
      tumors were made before and after each of three equal doses cumulating to 0.1,
      0.2 and 0.3 mmol Gd-complex per kg body weight. Quantitation of MRI contrast was
      limited to homogeneous brain metastases larger than 3 mm (n = 246). Post-Gd MRI
      contrast doubled with dose escalation from 0.1 to 0.3 mmol/kg and also increased
      with lesion size, by a factor of 2.5 between metastases of 3 and 16 mm diameter,
      that is after correcting for partial volume effect. At 0.2 and 0.3 mmol/kg the
      respective numbers of visible metastases increased by 15% and 43% compared with
      0.1 mmol/kg (p < 0.0001, both). Image contrast figures differed significantly
      between doses (p = 0.018). Both the number of metastases and the image contrast
      is significantly higher when dose escalation is performed. It is indicated that
      the number of detected metastases will increase further at Gd doses beyond 0.3
      mmol/kg. Post-Gd MRI contrast increases with lesion size, to an extent that can
      not be attributed to partial volume attenuation.

PMID- 9253998
TI  - MRI of pulmonary embolism using Gd-DTPA-polyethylene glycol polymer enhanced 3D
      fast gradient echo technique in a canine model.
AB  - This study was to evaluate the accuracy of MR angiography (MRA) using a Gd-DTPA
      polyethylene glycol polymer (Gd-DTPA-PEG) with a 3D fast gradient echo (3D fgre)
      technique in diagnosing pulmonary embolism in a canine model. Pulmonary emboli
      were created in six mongrel dogs (20-30 kg) by injecting tantalum oxide-doped
      autologous blood clots into the femoral veins via cutdowns. MRI was performed
      with a 1.5 T GE Signa imager using a 3D fgre sequence (11.9/2.3/15 degrees)
      following intravenous injection of 0.06 mmol Gd/kg of Gd-DTPA-PEG. The dogs were
      euthanized and spiral CT of the lungs were then obtained on the deceased dogs.
      The MRI images were reviewed independently and receiver-operating-characteristic
      (ROC) curves were used for statistical analysis using spiral CT results as the
      gold standard. The pulmonary emboli were well visualized on spiral CT. Out of 108
      pulmonary segments in the six dogs, 24 contained emboli >2 mm and 27 contained
      emboli < or = 2 mm. With unblinded review, MRI detected 79% of emboli >2 mm and
      only 48% of emboli < or = 2 mm. The blinded review results were significantly
      worse. Gd-DTPA-PEG enhanced 3D fgre MRI is potentially able to demonstrate
      pulmonary embolism with fairly high degree of accuracy, but specialized training
      for the interpretations will be required.

PMID- 9253999
TI  - Analysis of tracer transit in rat brain after carotid artery and femoral vein
      administrations using linear system theory.
AB  - Determination of tissue perfusion rates by MRI bolus tracking methods relies on
      the central volume principle which states that tissue blood flow is given by the
      tissue blood volume divided by the mean tracer transit time (MTT). Accurate
      determination of the MTT requires knowledge of the arterial input function which
      in MRI experiments is usually not known, especially when using small animals. The
      problem of unknown arterial input can be circumvented in animal experiments by
      directly injecting the contrast agent into a feeding artery of the tissue of
      interest. In the present article the passage of magnetite nanoparticles through
      the rat cerebral cortex is analyzed after injection into the internal carotid
      artery. The results are discussed in the framework of linear system theory using
      a one-compartment model for brain tissue and by using the well characterized
      gamma-variate function to describe the tissue concentration profile of the
      contrast agent. The results obtained from the intra-arterial tracer
      administration experiments are then compared with the commonly used intra-venous
      injection of the contrast agent in order to estimate the contribution of the
      peripheral circulation to the MTT values in the latter case. The experiments were
      analyzed using a two-compartment model and the gamma-variate function. As an
      application perfusion rates in normal and ischemic cerebral cortex of
      hypertensive rats were estimated in a model of focal cerebral ischemia. The
      results indicate that peripheral circulation has a significant influence on the
      MTT values and thus on the perfusion rates, which cannot be neglected.

PMID- 9254000
TI  - In vivo animal tests of an artifact-free contrast agent for gastrointestinal MRI.
AB  - A variety of shortcomings are associated with most currently used
      gastrointestinal contrast agents for magnetic resonance imaging (MRI). Artifacts
      resulting from peristalsis and other motions in the abdominal region are produced
      by many positive contrast agents (which increase signal intensity). Although this
      is not a problem for negative contrast agents (which decrease signal intensity),
      some negative contrast agents produce magnetic susceptibility artifacts that are
      especially pronounced at high field strength and with gradient echo pulse
      sequences. These susceptibility artifacts are produced by both paramagnetic and
      diamagnetic agents. It has been demonstrated in phantoms, however, that
      susceptibility matching can be used to produce contrast agents with desirable
      relaxation and contrast properties but without deleterious susceptibility
      artifacts. We now report results of animal tests of such an oral contrast agent,
      consisting of a suspension of superparamagnetic iron oxide particles and
      diamagnetic barium sulfate particles, compared to individual suspensions of the
      iron oxide and of the barium sulfate. Iron oxide was the least effective and the
      matched susceptibility mixture was the most effective for the intestine, which
      has traditionally been the most difficult region of the GI tract to visualize
      clearly. Matched susceptibility mixtures, which are inherently able to yield
      images free of susceptibility artifacts without compromising contrast, show
      promise of being improved oral negative contrast agents for use in
      gastrointestinal MRI.

PMID- 9254001
TI  - A general method for measurement of the time integral of variant magnetic field
      gradients: application to 2D spiral imaging.
AB  - A new method is proposed by which the time integral of time-varying magnetic
      fields in different voxels can be determined by MRI. A further processing step is
      employed which enables the integral of the magnetic field gradients experienced
      by groups of voxels to be deduced. Analysis of the theoretical background and
      complete simulations have been used to assess the limitations of the technique
      and the method is applied to the measurement of a 2D spiral k-space trajectory
      and also of its 1D components. These measured trajectories have been used to
      reconstruct images from experimental spiral-scan raw data of a phantom acquired
      using the 2D spiral k-space trajectory. Comparisons of the resulting images are
      made with the image reconstructed using the corresponding theoretical trajectory.
      The importance of the repeatability, reliability and accuracy of the technique is
      demonstrated.

PMID- 9254002
TI  - Image registration of MR and CT images using a frameless fiducial marker system.
AB  - A new system of fiducial stereotactic markers that can easily be adapted to
      various imaging modalities without losing image registration was developed and
      tested. Utilizing MR and CT imaging the accuracy of the new system was evaluated
      with phantom studies and preliminary patient studies. The markers are clearly
      visible without artifacts on both imaging modalities. The clear delineation of
      the marker dots on the images enables an accurate automated marker detection.
      Using the marker system, image registration was found to yield an accuracy of up
      to 1 mm, depending on the imaging modality and the employed marker arrangement.
      The presented marker system shall improve patient comfort in comparison to
      conventional fixed stereotactic frames if repeated, highly accurate registrations
      are necessary over longer periods.

PMID- 9254003
TI  - In vivo and ex vivo study of metabolic and cellular effects of 5-fluorouracil
      chemotherapy in a mouse mammary carcinoma.
AB  - The effect of 5-fluorouracil (5FU) on the 31P nuclear magnetic resonance (NMR)
      profile of a mouse mammary carcinoma, implanted on the foot of CH3/He mice, was
      studied both in vivo and in perchloric acid extracts. In vivo, significant
      increases in the ratios, nucleotide triphosphate:inorganic phosphate (Pi) (p <
      0.02) and phosphocreatine:Pi (p < 0.005), were observed 48 h after 5FU, relative
      to control. Two readily resolvable peaks were observed in the phosphomonoester
      region of the in vivo NMR spectrum, phosphocholine (PC) and a peak (denoted PME')
      comprised of mainly phosphoethanolamine (PE). PME':PC was significantly elevated
      relative to control from 24 h to 168 h (p < 0.0001 at 48 h). Perchloric acid
      extract data indicate that the change in this ratio was due to an increase in the
      PE concentration rather than a decrease in PC. PE increased from 0.56 +/- 0.11
      micromol/g tissue in controls to 0.95 +/- 0.29 micromol/g tissue 48 h after 5FU
      (p < 0.006). Perchloric acid extracts also revealed a significant increase in
      phosphodiesters. Glycerophosphocholine increased from 0.82 +/- 0.24 micromol/g
      tissue in controls to 1.82 +/- 0.61 micromol/g tissue in 5FU treated tumors after
      48 h (p < 0.002), and glycerophosphoethanolamine increased from 0.25 +/- 0.06
      micromol/g tissue in controls to 0.36 +/- 0.10 micromol/g tissue in treated
      tumors (p < 0.004). These changes suggest that ethanolamine and choline
      containing metabolites in this tumor may be metabolized via different pathways.
      Cell cycle analysis showed only relatively small changes in cell cycle
      distribution and apoptotic fraction following 5FU.

PMID- 9254004
TI  - Relationship between pulse sequences and signal intensity of joint fluid in the
      gradient-echo MR imaging.
AB  - To depict the labrum and meniscus in terms of contrast to joint fluid by
      increasing its signal intensity, we examined in vitro and in a human subject the
      good imaging conditions of gradient-echo magnet resonance by using a 1.0 Tesla
      superconducting imager (Shimadzu). In our in vitro study, 3 types of joint fluid
      and physiological saline were imaged together with PVA gel (as the substitute for
      surrounding soft tissue), by using either the STAGE, SSFP, or STERF method, and
      with several TR's (repetition time); and mean signal intensity was obtained. In
      order to confirm the findings of the in vitro study, a human study was conducted:
      physiological saline was injected into a shoulder joint, and axial planes were
      depicted under the conditions equivalent to those of the in vitro study. With the
      STERF method, signal intensity of the fluid was high at any flip angle, but PVS
      gel and the surrounding soft tissues such as muscles were rarely depicted. With
      the STAGE and SSFP methods, depiction of the fluid, PVA gel, and the surrounding
      soft tissues were possible by setting an appropriate flip angle for TR: With the
      STAGE method (a spoiled gradient echo sequence), good imaging was possible by
      selecting small flip angle, regardless TR. Therefore, because of easiness in
      selecting conditions, the STAGE method is considered to be the best for
      diagnostic scanning.

PMID- 9254005
TI  - Early cerebral-metabolite quantification in perinatal hypoxic-ischaemic
      encephalopathy by proton and phosphorus magnetic resonance spectroscopy.

PMID- 9254006
TI  - Angiosarcoma of the liver: MR imaging pre- and post-chemotherapy.
AB  - Angiosarcoma of the liver is a rare tumor of mesenchymal origin. We report the MR
      appearance of angiosarcoma of the liver on T1-weighted, T2-weighted, and serial
      gadolinium enhanced spoiled gradient echo images pre- and post-intravenous
      chemotherapy. On pre-treatment images, angiosarcoma lesions were well defined,
      high signal with central regions of low signal on T2-weighted images, and showed
      peripheral nodular enhancement on serial post gadolinium images. Lesions
      resembled hemangiomas, however low signal central regions on T2-weighted images
      was a distinguishing feature. Post-treatment images acquired 11, 15, and 17
      months after initiation of therapy, demonstrated decrease in diameter or
      resolution of angiosarcoma masses. Lesions increased in signal on T1 weighted
      images and decreased in signal on T2 weighted images approaching the signal
      intensity of liver. Treated liver lesions enhanced negligibly on gadolinium
      enhanced images.

PMID- 9254007
TI  - Organization and sequence of the human gene for the mitochondrial citrate
      transport protein.
AB  - The citrate (tricarboxylate) carrier transports citrate (or other
      tricarboxylates) across the inner membranes of mitochondria in an electroneutral
      exchange for malate (or other dicarboxylic acids). We have determined the
      sequence of the human citrate transporter gene from overlapping genomic clones
      generated by polymerase chain reactions by use of primers and probes based on the
      rat cDNA sequence and on emerging sequences. The gene is spread over 2.8 kb of
      human DNA and is divided into eight exons. All the introns are located at the
      level of the sequences coding for the extramembranous loops (and not for the
      transmembrane segments) of the mature protein. The open reading frame of the
      human gene encodes the mature protein consisting of 298 amino acids, preceded by
      a presequence of 13 amino acids to help to target it into mitochondria. 84
      identities and 106 highly conservative substitutions are present in CTPs from man
      to yeast. In addition, we have determined the sequences of two human pseudogenes
      related to the citrate carrier gene encompassing the coding sequence of the gene
      between nucleotides 260 and 720.

PMID- 9254008
TI  - Genomic structure and sequence analysis of the valyl-tRNA synthetase gene of the
      Japanese pufferfish, Fugu rubripes.
AB  - The genomic sequence and exon-intron organisation of the valyl-tRNA synthetase
      gene in the Japanese pufferfish, Fugu rubripes, have been determined. This single
      copy Fugu gene spans 8.5 kb, about 2.5 times smaller than that in man (21 kb). It
      contains 29 exons, with the largest intron being 1008 bp. The predicted
      polypeptide consists of 1217 amino acids, with a molecular weight of 138 kD and
      an isoelectric point of 7.27. It shares 40% identity in the overlapping region
      with its homolog in bacteria, 47% with yeast, and 67% with man. The Fugu gene has
      an additional N-terminal sequence which shows strong similarity to elongation
      factory-1gamma, a feature it shares only with the human sequence, but not with
      any other lower eukaryote or prokaryote studied so far. This N-terminal segment
      is encoded in the first six exons, suggesting their capture by a translocation
      through introns. Indeed, the acquisition of extra domains to perform related
      functions in RNA splicing and translation of polypeptides has already been
      observed in other aminoacyl-tRNA synthetases. Two cDNA sequences of human valyl
      tRNA synthetase have been published, with discrepancies between them. Aided by
      comparisons with the Fugu gene, three of these discrepancies have been resolved,
      involving the elucidation of the sequence and positions of two introns. This
      compact vertebrate genome has demonstrated its value as a tool for the analysis
      of genes at the genomic level.

PMID- 9254010
TI  - A novel algorithm for the search of 5S rRNA genes in DNA databases: comparison
      with other methods and identification of new potential 5S rRNA genes.
AB  - We report here a new algorithm for the identification of 5S rRNA genes in DNA
      databases. Based on an improved version of the general weight matrix method, this
      search procedure relies on the recognition of three informative regions within 5S
      rRNA genes, and on the weighted evaluation of the distance between them. As an
      additional step, the algorithm extends the weight matrix analysis to the full
      length 5S rRNA sequence. This combined strategy, which includes a fast, but
      poorly selective, preliminary search procedure and an auxiliary step, that is
      slow but highly selective, strongly reduces the number of false positive
      instances, yielding a total false positive rate of 0.00076%. On the other hand,
      97.5% of the 1045 known 5S rRNA genes were correctly recognized by this
      algorithm, and 29 previously unidentified potential 5S rRNA sequences were
      uncovered. A detailed analysis of these candidate sequences, including prediction
      of 5S rRNA secondary structure and checking for the presence of transcriptional
      termination signals, showed that eight of them correspond to authentic 5S rRNA
      genes. The performance of this specialized algorithm for the detection of 5S rRNA
      genes was compared with that of the general hidden Markov model search procedure.
      Due to their utilization of different filtering rules, the two approaches proved
      to be highly complementary. Their combined use will thus provide a very effective
      tool for the detection of dispersed 5S rRNA genes, either active or inactive, in
      the vertebrate genome.

PMID- 9254009
TI  - Cloning and characterization of novel gene, DCRR1, expressed from Down's syndrome
      critical region of human chromosome 21q22.2.
AB  - The new gene, DCRR1, from the proximal part of the Down's syndrome critical
      region (DCR) was identified by the GRAIL analysis of the 97-kb nucleotide
      sequence of two P1 DNAs and the cDNA for DCRR1 gene was cloned. A 7.36-kb cDNA
      encodes the imcompleted open reading frame composed of 1941 amino acid residues
      (220.2 kDa). The deduced amino acid sequence contains the conserved domain for
      protein phosphatases at the N-terminus. The domain encoding the rod-like tail of
      a myosin heavy chain was also found near the C-terminal region besides the
      signature for an actin binding protein, profilin, suggesting its possible role as
      a microtuble-associated protein. Two different sizes (7.9 and 9.0 kb) of mRNAs
      were detected in the poly(A)+ RNA from abundant tissues by the Northern analysis.
      The smaller transcript was only transcribed at a high level in the testis. The
      imbalance of the DCRR1 gene dosage may contibute to the pathogenesis of Down's
      syndrome.

PMID- 9254011
TI  - Nucleotide sequence of ToxPK1 gene from Toxoplasma gondii.
AB  - We report here for the first time a complete nucleotide sequence (6.8 kb) of a
      protein kinase gene (ToxPK1) from the obligate intracellular protozoan parasite
      of man, Toxoplasma gondii. This gene comprising putatively of 9 exons and 8
      introns forms the Toxoplasma gene with the largest number and size of introns
      reported so far. The predicted protein with 508 amino acids contains the 15
      invariant residues as well as the characteristic motifs specific to protein
      serine/threonine kinases. Homology-based computational comparisons suggested that
      TOXPK1 belongs to or closely resembles the SNF1 subfamily of protein
      serine/threonine kinases. Based on the functions of SNF1 homologs in other
      organisms and our RT-PCR results, it is likely that TOXPK1 may be transiently
      expressed to up-regulate glycogen biosynthesis during the development of
      tachyzoites into bradyzoites.

PMID- 9254012
TI  - An ABC-transporter system homolog in an organism of the phylogenetic domain
      Archaea.
AB  - A cluster of genes was identified in an archaeal organism, the methanogen
      Methanosarcina mazei S-6, that was a homolog of the ABC-transporter system loci
      of several organisms belonging to the phylogenetic domain Bacteria. The gene
      number, size, and organization were also similar. The proteins encoded by these
      genes were similar in structure, hydrophilicity-hydrophobicity profiles, and
      motifs to the equivalent components of homolog systems in bacteria and eucarya.

PMID- 9254013
TI  - Isolation of the mouse cDNA homologous to the human EXT1 gene responsible for
      Hereditary Multiple Exostoses.
AB  - We have cloned and sequenced the mouse cDNA homologous to the human Hereditary
      Multiple Exostoses (EXT1) gene. The mouse homolog shows 94% similarity at the
      nucleotide level and 99% similarity at the protein level compared to the human
      gene. The 5' UTRs are unusually conserved for non-coding sequences showing 94%
      similarity compared to 80% for the 3' UTRs. The high level of evolutionary
      conservation between the EXT1 proteins as well as the 5' UTR suggests that each
      plays an important and related role in both species.

PMID- 9254014
TI  - Cloning and sequence analysis of a cDNA encoding bovine ribosomal protein P2:
      predicted alpha-helices and potential phosphorylation sites.
AB  - A cDNA corresponding to bovine acidic ribosomal P2 was cloned and sequenced. It
      encodes a polypeptide 115 amino acids long. The secondary structure prediction
      shows that bovine P2 contains a large part of the protein domain as alpha
      helices. Alignment and analysis of 16 eukaryotic P2 proteins of 12 species reveal
      that there are three predicted alpha-helical regions conserved in almost all P2
      proteins; helix 1 and helix 2 may be part of a helix-turn-helix structure.
      Sequence analysis indicates that there are seven serine residues in bovine P2
      protein which are potential phosphorylation sites for a variety of Ser/Thr
      kinases. A few such sites appear at similar positions in many P2 proteins. The
      antigenic region is predicted to be located in the stretch of acidic amino acids
      in the vicinity of the C-terminus of P2. The predicted alpha-helical structures,
      potential phosphorylation sites and antigenic regions of the P2 protein provide
      some insights into the structure of P2 protein and deserve further experimental
      study.

PMID- 9254015
TI  - A cell cycle-regulated histone H3 gene of alfalfa with an atypical promoter
      structure.
AB  - The control of cell cycle expression of histone genes in plants is incompletely
      understood. A new histone H3 gene was cloned from alfalfa (Medicago sativa) that
      codes for the replication-dependent histone H3.1 variant protein. Despite lacking
      all promoter sequence motifs that have been associated with cell cycle-dependent
      histone gene expression in plants, northern analysis of synchronized cells
      clearly linked gene expression to DNA replication. TTAATNA was recognized as a
      new sequence element in the 3' untranslated regions of this and all other cell
      cycle-dependent histone H3 genes of dicotyledonous plants. It is not found in the
      replication-independent histone H3 genes.

PMID- 9254016
TI  - Sequence of a human cDNA encoding Cab45, a Ca2+-binding protein with six EF-hand
      motifs.
AB  - We report the sequence of a human cDNA encoding a deduced 362 amino acid protein
      with six EF-hand calcium-binding motifs. The protein is a likely human
      counterpart of the Cab45 protein recently identified in the 3T3-L1 mouse
      adipocyte cell line [Scherer et al. (1996), J. Cell Biol. 133, 257-268],
      displaying 87% aa and 83% nt identity with this sequence. The mRNA for human
      Cab45 is detected ubiquitously in tissue Northern blots.

PMID- 9254017
TI  - IS element ISXC6 of Xanthomonas campestris pv. campestris.
AB  - An insertion sequence element, ISXC6, was isolated from Xanthomonas campestris
      pv. campestris 17 (Xc17). Sequence analysis showed that it is 1,500 bp long and
      has 20-bp perfect inverted repeat ends. Upon transposition, a direct repeat
      TAATTC was generated, flanking this IS. No significant homology was observed
      between this sequence and other sequences in database. Results of Southern
      hybridization showed that multiple copies of ISXC6 were present in 7 strains of
      Xanthomonas examined.

PMID- 9254018
TI  - Further sequence analysis of the DNA regions with the Rhodococcus 20S proteasome
      structural genes reveals extensive homology with Mycobacterium leprae.
AB  - The sequence of the respective DNA regions downstream of the 20S proteasome
      structural genes prcB1A1 (6 kb) and prcB2A2 (3.3 kb) of Rhodococcus erythropolis
      NI86/21 were determined. A highly conserved gene organization was observed
      between the two clusters which differed significantly in G + C content (68.8%
      versus 62.6%). Several ORFs were homologues of putative genes previously
      identified by genomic sequencing of the equivalent DNA in the related
      nocardioform actinomycete, Mycobacterium leprae, and thought to be specific for
      this pathogen. Three ORFs (ORF8(1), ORF8(2), ORF12[1]) without a counterpart in
      M. leprae were found. No significant homology to known sequences including
      proteasome-related gene products was detected, except for ORF9(1) and ORF9(2)
      which display a high level of sequence identity with a partially sequenced ORF in
      Streptomyces chrysomallus. These downstream ORFs also show a significant level of
      sequence homology with the ORF6(1) and ORF6(2) which are located upstream of the
      proteasome structural genes in the respective clusters.

PMID- 9254019
TI  - A method to direct sequence cosmid LAWRIST16 clones.
AB  - We developed a new cycle condition method optimized for direct sequencing
      LAWRIST16 cosmid clones based on dye terminator and dye primer cycle sequencing
      chemistries. We report a direct comparison of the two most widely used sequencing
      polymerase enzymes (AmpliTaq FS and Thermosequenase). The sequencing data
      obtained is of high quality and we believe this method could be routinely used in
      large scale sequencing facilities.

PMID- 9254020
TI  - The cloning and sequencing of an ovine c-myc cDNA.
AB  - We report the cloning of an ovine c-myc cDNA. The clone was isolated from a
      bovine leukemia virus-infected cell line (YR2) cDNA library cloned in the lambda
      gt10 vector. The clone encodes the full length c-Myc protein made of 439 amino
      acids with 93, 96, 92 and 93% similarity with human, feline, murine and rat c-Myc
      proteins, respectively.

PMID- 9254021
TI  - Nucleotide sequence of equine MxA cDNA.
AB  - A 2.6 kb cDNA species has been isolated from a cDNA library prepared from
      interferon-alpha stimulated equine peripheral blood leucocytes and the nucleotide
      sequence determined. The cDNA has a single open reading frame potentially
      encoding a 660 amino acid polypeptide showing a high degree of homology with
      known mammalian Mx proteins, including the possession of three consensus GTP
      binding motifs. The protein has a calculated pI = 6.1 and in accordance with
      proposed nomenclature we have designated it equine MxA.

PMID- 9254022
TI  - Staurosporine differentiated human SH-SY5Y neuroblastoma cultures exhibit
      transient apoptosis and trophic factor independence.
AB  - The use of chemically differentiated neuroblastoma cells in the study of neuronal
      function has become a common alternative to primary neuronal cell cultures in
      recent years, particularly in the area of cell death. Staurosporine, a
      nonselective protein kinase inhibitor, has been demonstrated to be a particularly
      strong inducer of differentiation in the SH-SY5Y human neuroblastoma cell line.
      However, at present, no data exist on the long-term effects of this compound. We
      have compared the effects of staurosporine with 12-O-tetradecanoyl phorbol-13
      acetate and retinoic acid in terms of long-term cell viability and neuronal
      function in the SH-SY5Y cell line. In the presence of serum, staurosporine
      treated cells underwent apoptosis, which ultimately resulted in total cell loss.
      In contrast, when cultured in defined serum-free medium, a cessation of apoptosis
      occurred after approximately 1 week, at which point viability could be maintained
      in excess of 1 month. The addition of aurintricarboxylic acid, which has been
      demonstrated to prevent apoptosis in a variety of cell models, completely
      prevented both apoptosis and differentiation in staurosporine-treated cells both
      under serum-supplemented and serum-free conditions. Apoptosis was not prevented
      by the protein synthesis inhibitor, cycloheximide. The removal of staurosporine
      from the culture medium after 3 weeks had no effect on cellular morphology,
      function, or proliferation, indicating that the attained neuronal phenotype was
      terminal. Voltage-gated calcium channel sensitivity, used as a measurement of
      neuronal function, was highest in staurosporine-treated cells. On the basis that
      apoptosis and neurotrophin independence are hallmarks of the maturation of dorsal
      root ganglion neurons, results suggest that staurosporine-differentiated SH-SY5Y
      cells may bear a similar phenotype to that found in vivo. Furthermore, this model
      may provide for an excellent means of obtaining a stable and homogenous
      population of postmitotic monoaminergic neurons for investigating neuronal
      function and differentiation.

PMID- 9254023
TI  - Ketamine modulation of the temporal pattern of discharges and spike train
      interactions in the rat substantia nigra pars reticulata.
AB  - This study compares the temporal pattern of discharges of extracellularly
      recorded substantia nigra pars reticulata (SNr) single units in two experimental
      conditions: Equithesin- and ketamine-induced anesthesia. The analysis of the
      statistical properties of the spike trains recorded in the Equithesin group of
      animals showed that this experimental condition could be considered as a control
      condition with respect to previous data reported in the literature. We
      investigated the glutamatergic modulation of SNr activity at spike train level in
      a steady-state condition by using the anesthetic agent ketamine, which is a
      noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) glutamatergic
      receptors. The most relevant effect of ketamine at single unit level was to
      induce burst discharges, with an intraburst frequency rate near 50 Hz,
      specifically in units characterized by an initial long refractoriness in the
      Equithesin condition. The other classes of single units tended to discharge at a
      higher rate without any significant change in their temporal pattern of firing.
      Simultaneous recording of the spike trains of 108 SNr pairs (46 and 62 during
      Equithesin and ketamine condition, respectively) were equally distributed between
      pairs of units simultaneously recorded from the same electrode and from distinct
      electrodes at a distance up to 400 microm in the same hemisphere. Ketamine
      induced a significant increase in the number of pairs with synchronous firing
      (from 4 to 49%), which was strongly, but not exclusively, associated with an
      increased tendency to fire in bursts. Neighboring cells tended to fire with a
      similar pattern in either condition of recording, whereas synchronous firing
      between distant cells was observed only during ketamine condition.

PMID- 9254024
TI  - A simulation study of the electromyographic volley at initiation of rapid
      isometric contractions in the first dorsal interosseous muscle.
AB  - Monopolar surface electromyograms (EMGs) of rapid isometric abduction of the
      first dorsal interosseous muscle (FDI) were initiated from an EMG volley that was
      characterized by a negative potential lasting over several tens of milliseconds.
      An EMG model was developed to study how the EMG volley was generated. EMGs were
      defined as the linear summations of surface-recorded action potential trains
      originating from single motor units (MUs). All action potential trains had the
      same discharge pattern but different recruitment thresholds, depending on the
      potential amplitude. Real action potentials in single MUs in FDI were recorded
      with a monopolar surface electrode, one of which was used as a prototype wave in
      simulation. The model predicted an initial negative potential comparable to that
      of the EMG volley observed in rapid contractions of FDI. Results from our
      simulation studies suggest that the EMG volley is caused by at least two
      independent factors: (1) the negative phase of the action potential is greater in
      area than the positive one, in which the effect is enhanced by the high discharge
      rate of many MUs; (2) many MUs are recruited within a short time in an orderly
      fashion starting from those with small action potentials to those with large
      ones.

PMID- 9254025
TI  - The affinity of lipid-coated microbubbles for maturing brain injury sites.
AB  - The availability of a vehicle to deliver lipid soluble agents to a brain injury
      site may be of potential value in management of brain injury. This work describes
      the aggregation of intravenously administered Lipid-Coated Microbubbles (LCM) in
      the injury site following an experimental radiofrequency rat brain lesion. The
      bubbles can be identified around the region of the injury after the lesion has
      matured at least 48 h. The greatest bubbles density is evident after the lesion
      has matured for 10 days. This bubble density, reflecting "affinity," decreases to
      a plateau level from the second to the third week after injury. In order to
      investigate the potential relationship of bubble influx to posttraumatic
      astrocytosis and to cell turnover in the region, we utilized dual-channel laser
      scanning confocal microscopy to track both bubble influx into the region and
      concomitant Glial Fibrillary Acidic Protein (GFAP) expressing astroctyte cell
      distribution. Cell turnover was assayed in separate sections using
      immunohistochemical staining of Proliferating Cell Nuclear Antigen (PCNA). We
      suggest a relationship between the LCM affinity and reactive astrocytes, but
      found no affinity of LCM for cells which stained positive with PCNA.

PMID- 9254026
TI  - Delayed decrease of calbindin immunoreactivity in the granule cell-mossy fibers
      after kainic acid-induced seizures.
AB  - Kainic acid (KA) administration induces an abnormal excitation and spontaneous
      recurrent seizures. Alterations of granule cell properties may be potential
      mechanisms. In this study, dynamic alterations of calbindin, a calcium binding
      protein particularly abundant in the granule cells, have been investigated
      immunocytochemically in the rat hippocampus after the KA-induced seizures. The
      calbindin immunoreactivity decreased slightly in the CA1/CA2 fields already after
      1 and 3 days, and was lost partly or completely in the pyramidal layer after 10
      days. From day 21, the calbindin immunoreactivity decreased in dendrites and soma
      of the granule cells and mossy fibers. The alterations remained at least to day
      90, while no evident neuronal loss occurred in the granule cells. This may
      reflect a disturbance of calcium homostasis in the granule cells after seizures.
      The delayed decrease of calbindin has a time course similar to the occurrence of
      spontaneous recurrent seizures, suggesting a possible correlation between the two
      events.

PMID- 9254027
TI  - Synaptophysin immunoreactivity in the aging rat pituitary gland.
AB  - The density of synaptophysin (SN)-immunoreactivity (IR) was examined in pituitary
      glands of aging male Sprague-Dawley rats. SN-IR was observed as dense dots among
      endocrine cells of the intermediate lobe, while the neural lobe contained
      numerous, highly dense immunopositive regions. Some anterior lobe secretory cells
      contained SN-IR within the cytoplasm, suggestive of the presence of the protein
      in secretory granules, but no dot-like staining was observed between endocrine
      cells of that region. A quantitative analysis of the dot-like SN-immunostaining
      within the intermediate lobe found that tissue from groups of rats aged 13
      months, or 15-17 months, contained significantly fewer SN-immunopositive areas
      than did tissues from 8-month-old animals. Diminished SN immunostaining is
      suggestive of reduced numbers of synapses in the intermediate lobe, which may
      lead to alterations in regulation of pituitary hormone secretion from endocrine
      cells in the older animals.

PMID- 9254028
TI  - Intra-ventral tegmental area administration of H7 delays, but does not prevent
      the development of cocaine-induced sensitization.
AB  - Previous studies have suggested that increased protein kinase C activity in the
      ventral tegmental area (VTA) may play a role in the acute and development of the
      sensitized behavioral responses to cocaine. The present study was conducted to
      further characterize the role of protein kinases in the development of
      sensitization. Animals received injections of saline or the nonspecific protein
      kinase inhibitor H7 into the VTA before each of their four daily systemic
      injections of saline or cocaine. Animals were tested for sensitization with a
      challenge injection of systemic cocaine after a withdrawal period of 24 h or 1
      week. Tests for sensitization included monitoring cocaine-induced motor activity
      and/or dopamine concentrations in the nucleus accumbens, as measured by in vivo
      microdialysis. Pretreatment with H7 in the VTA attenuated the acute motor
      stimulant response to cocaine as well as the cocaine-induced increase in
      extracellular dopamine in the nucleus accumbens. In addition, the augmented
      increase in dopamine in the nucleus accumbens of cocaine-sensitized animals was
      prevented in animals pretreated with H7 before each of their daily cocaine
      injections, when tested after a 24 h withdrawal. However, when tested after a 1
      week withdrawal, animals demonstrated sensitization to both the cocaine-induced
      increase in motor activity and the cocaine-induced increase in dopamine in the
      nucleus accumbens regardless of whether they received intra-VTA saline or H7
      before each of their daily cocaine injections. These data suggest that injection
      of a protein kinase inhibitor into the VTA delays, but does not prevent the
      development of cocaine-induced behavioral sensitization.

PMID- 9254029
TI  - Possible involvement of catalase in the protective effect of interleukin-6
      against 6-hydroxydopamine toxicity in PC12 cells.
AB  - We examined the effects of various neurotrophic factors and cytokines on 6
      hydroxydopamine (6-OHDA)-induced toxicity in PC12 cells. Exposure of PC12 cells
      to 6-OHDA resulted in a concentration- and time-dependent cell death, as
      evidenced by the release of lactate dehydrogenase into the culture medium.
      Addition of catalase, but not superoxide dismutase, to the culture medium
      protected PC12 cells from the 6-OHDA-induced toxicity. Interleukin (IL)-6
      provided a dose-dependent protection against the 6-OHDA toxicity, as did nerve
      growth factor (NGF). In addition, basic fibroblast growth factor and dibutyryl
      cyclic AMP partially protected PC12 cells from 6-OHDA toxicity. Neither IL
      1alpha, IL-2, IL-4, transforming growth factor-beta, nor leukemia inhibitory
      factor had any effect. The protective effect of IL-6 was attenuated by 3-amino
      1,2,4-triazole, an inhibitor of catalase. These results suggest that IL-6 may
      protect PC12 cells against the 6-OHDA toxicity by activating free radical
      detoxifying mechanisms, such as catalase activity.

PMID- 9254030
TI  - Functional development of the vibrissae somatosensory system of the rat: (14C) 2
      deoxyglucose metabolic mapping study.
AB  - Functional development of the rat whisker somatosensory system was studied by
      using the (14C) 2-deoxyglucose (2DG) metabolic mapping technique. Restrained rat
      pups had their left mystacial vibrissae stroked for 30 minutes and their brains
      harvested, sectioned, and autoradiographed from the level of the lower medulla to
      the frontal cortex. Subjects were tested at postnatal days (PNDs) 0-9 and 21. At
      birth, all subjects exhibited a significant increase of 2DG uptake in the left
      spinal trigeminal nuclei, the principal trigeminal sensory nucleus, and a portion
      of the right ventral posteromedial thalamic nucleus. The primary somatosensory
      cortex exhibited significant 2DG uptake contralateral to stimulation by PND 6,
      followed by the secondary somatosensory cortex at PND 7. The pattern of 2DG
      uptake in the somatosensory cortices became more intense and well defined by PND
      9. Given that the somatosensory system develops in an orderly fashion from the
      periphery to higher brain structures, the present results show that brain
      structures mediating whisker sensory input are not metabolically active until
      projections from lower somatosensory centers are established. Neurons become
      responsive to whisker stimulation in the subcortical structures at birth and in
      the somatosensory cortex a few days later. This cortical activity follows the
      organization of the upper tier of thalamocortical fibers into a "barrelfield."
      Moreover, there is a gradual enhancement in functional activity of the vibrissa
      neurons at different somatosensory nuclei as rats mature. The present study
      elucidates the time course of functional development in the rat somatosensory
      system.

PMID- 9254031
TI  - Differential distribution of (GABA)A receptor subunits on bulbospinal
      serotonergic and nonserotonergic neurons of the ventromedial medulla of the rat.
AB  - Spinally projecting neurons of the ventromedial medulla (VMM) compose an
      important efferent pathway for the modulation of nociception. These neurons
      receive a substantial gamma-aminobutyric acid (GABA)-ergic input, but the GABA
      receptor that mediates this input is unknown. This study examined the
      distribution of GABA(A) receptor alpha1 and alpha3 subunits in serotonergic and
      nonserotonergic neurons of the VMM that project to the dorsal horn in the rat. A
      pledget of Gelfoam soaked in Fluoro-Gold was placed at the thoracolumbar junction
      of the spinal cord to label spinally projecting neurons. Alternate sections of
      the medulla were then incubated with a mixture of antisera to either serotonin
      and the alpha1 subunit, or to serotonin and the alpha3 subunit of the GABA(A)
      receptor. Nearly 30% of spinally projecting neurons in the VMM were
      immunoreactive for the alpha1 subunit. A similar percentage of spinally
      projecting neurons in the VMM were immunoreactive for the alpha3 subunit,
      although diffuse cellular labeling combined with intense staining of processes in
      the neuropil precluded a rigorous semi-quantitative estimation of this
      population. No alpha1-subunit-immunoreactive neurons colocalized serotonin. In
      contrast, serotonergic neurons were immunoreactive for the alpha3 subunit.
      However, these double-labeled neurons were a modest percentage of the
      serotonergic population. A small percentage of spinally projecting serotonergic
      neurons was immunoreactive for the alpha3 subunit. These results suggest that
      significant numbers of spinally projecting serotonergic and nonserotonergic
      neurons of the VMM possess GABA(A) receptors that differ in their respective
      subunit compositions and that both classes of neurons may mediate the
      antinociception produced by the microinjection of GABA(A) receptor antagonists in
      the VMM.

PMID- 9254033
TI  - Morphology of interneurons in the procerebrum of the snail Helix aspersa.
AB  - Terrestrial snails have a highly developed sense of olfaction. Because the
      procerebrum has a large number of cells and is located at the entry site of the
      olfactory nerve into the brain, the structure is thought to have a significant
      role in the processing of olfactory stimuli. The morphology of the procerebral
      neurons in the snail Helix aspersa was investigated through intracellular
      injections of biocytin. No formal categorization of neuronal types was possible,
      but some cells were seen to have neurites entirely intrinsic to the procerebrum,
      whereas others had both intrinsic and extrinsic arborizations, and still others
      had only extrinsic arborizations. These interneurons were previously thought to
      have arborizations restricted to the procerebral lobe. We demonstrated the extent
      of the neurite projections outside of the procerebral lobe by making focal
      injections of biocytin or Neurobiotin into various regions of the cerebral
      ganglion. This technique revealed subsets of cells that send neurites not only in
      the ipsilateral ganglion but also through the cerebral commissure into the
      contralateral cerebral ganglion. Our results demonstrate not only that the
      procerebral cell population is heterogeneous but also that the procerebrum
      interacts more directly with the rest of the central nervous system than was
      formerly believed.

PMID- 9254032
TI  - Regulation of developing dopaminergic axonal arbor size in three-dimensional
      reaggregate tissue culture.
AB  - The role of target availability in determining axonal size of the developing
      dopaminergic neuron was examined in three-dimensional reaggregate culture in
      which these neurons undergo normal neurochemical and morphological development.
      The ratio of striatal target cells to dopaminergic neurons was systematically
      increased from 2:1 to 50:1 (striatal to mesencephalic cells). These ratios
      provide sufficient target for quantitative survival of dopaminergic neurons
      similar to that seen in vivo. After 3 weeks in culture, dopamine levels increased
      linearly and proportionally to dopaminergic cell number over a 25-fold relative
      increase in target cell availability. The amount of neurotransmitter per
      dopaminergic cell remained constant, suggesting that the axonal arbor did not
      increase as a function of target availability. This conclusion was directly
      tested by morphological analysis of the dopaminergic axonal arbor in single
      aggregates containing between 0 and 45 dopaminergic cells under conditions in
      which sufficient target was not a factor in dopaminergic cell survival. As was
      the case with respect to dopamine concentration, axonal arbor size per cell
      remained constant in the face of increasing target availability. Thus,
      availability of target cells under these conditions, is not, per se, the limiting
      factor on the rate of growth of the developing dopaminergic axonal arbor.

PMID- 9254034
TI  - Transient fetal structure, the gangliothalamic body, connects telencephalic
      germinal zone with all thalamic regions in the developing human brain.
AB  - Previous studies reported that telencephalic proliferative zones contribute to
      the development of the pulvinar thalamic nucleus in the human brain (Rakic and
      Sidman [1969] Z. Anat. Entwicklungsgesch. 129:53-82). The present study examined
      their possible contribution to the development of other thalamic nuclei.
      Postmortem brain tissue from human fetuses ranging between 10.5 and 40 weeks of
      gestation (wg) was processed by Nissl staining, Golgi impregnation, and MAP2
      (microtubule-associated protein 2) immunocytochemistry. The gangliothalamic body,
      suggested to serve as a conduit for cells migrating from the ganglionic eminence
      to the thalamus, was found in the period from 15 to 34 wg in all rostrocaudal
      thalamic regions, particularly at the level of the anterior nuclear complex,
      mediodorsal and pulvinar nucleus, and in addition, the lateral geniculate
      nucleus. In Nissl-stained sections, the gangliothalamic body is a thin cellular
      layer situated beneath the thalamic surface, near the telencephalo-diencephalic
      junction. In Golgi- and MAP2-stained sections, it is a stream of mostly bipolar
      cells extending from the ganglionic eminence to the medial thalamus. In addition,
      MAP2-immunoreactivity confirms the neuronal nature of its cells. The present
      study further supports the hypothesis that certain neurons migrate from the
      ganglionic eminence to the thalamus through the transient gangliothalamic body
      during fetal development. Moreover, our data indicate that both the association
      (mediodorsal and pulvinar), as well as the anterior (limbic) and specific relay
      nuclei are potential recipients of the telencephalic neurons.

PMID- 9254035
TI  - Octavolateral neurons projecting to the middle and posterior rhombencephalic
      reticular nuclei of larval lamprey: a retrograde horseradish peroxidase labeling
      study.
AB  - The octavolateral area of lampreys, which receives primary fibers from the
      octaval and lateral line nerves, is involved in the premotor organization of body
      movements through secondary projections to the reticular formation. Here, the
      typology of neurons of the three octavolateral nuclei (ventral, medial, and
      dorsal) that putatively project to the middle and posterior rhombencephalic
      reticular nuclei were studied by retrograde transport of horseradish peroxidase
      (HRP) applied to these reticular nuclei. Several types of neurons were labeled in
      the ventral nucleus, both ipsilateral and contralateral to the site of HRP
      application. Some of these neurons showed a rather simple morphology (octavomotor
      neurons, monopolar cells), but most had more- or less-branched dendrites that
      were associated with one, or several, fields of terminal fibers in the
      octavolateral area. Unlike those of the ventral nucleus, labeled neurons of the
      medial nucleus were homogeneous in appearance (mostly pear-shaped). The dorsal
      nucleus was scarcely developed in larvae, as judged from the very simple and
      small labeled cells. The presence of terminal or "en-passant" boutons of
      secondary octavolateral fibers in the reticular area and the commissural nature
      of these fibers were also investigated by means of application of HRP or
      indocarbocyanine dye to the octavolateral nuclei. In addition, neurons of other
      alar plate nuclei that were labeled by the HRP application to the reticular
      nuclei (trigeminal descending root nucleus and solitary nucleus) were also
      characterized. The functional significance of these results is discussed.

PMID- 9254036
TI  - Constitutive expression of the 27-kDa heat shock protein (Hsp27) in sensory and
      motor neurons of the rat nervous system.
AB  - In this study, the constitutive expression of the 27-kDa heat shock protein
      (Hsp27) in the adult rat central nervous system has been examined by
      immunohistochemistry and by two-dimensional gel Western blot analysis. Hsp27
      immunoreactivity was observed primarily in motoneurons of cranial nerve nuclei
      and spinal cord, and in primary sensory neurons and their central processes.
      Also, Hsp27 immunoreactivity was present in neurons of the arcuate nucleus and of
      the reticular formation. However, only a subset of these neurons was Hsp27
      immunoreactive. Most general somatic efferent motoneurons of the hypoglossal
      nucleus and spinal motor columns and most special visceral efferent motoneurons
      of the cranial nerve nuclei were Hsp27-positive. In contrast, fewer general
      somatic efferent motoneurons for eye muscles were Hsp27-positive, and only a
      small proportion of general visceral efferent neurons, i.e., parasympathetic and
      sympathetic preganglionic neurons, were stained for Hsp27. Many pseudounipolar
      sensory neurons were Hsp27-immunoreactive, and the patterns of staining in
      central sensory nuclei suggested that specific subpopulations of sensory neurons
      contained Hsp27. The cellular distribution of Hsp27 was uniform throughout the
      cytoplasm, including the perikaryon, axon and dendrites, the latter often
      exhibiting varicosities or beading in distal processes. Western blot analyses
      revealed that at least three phosphorylated isoforms of Hsp27 were present in the
      spinal cord. These results suggest that constitutively expressed Hsp27 may be
      related to functional subpopulations of motoneurons and primary sensory neurons.

PMID- 9254037
TI  - Localization of neurons expressing substance P and neurokinin B gene transcripts
      in the human hypothalamus and basal forebrain.
AB  - In situ hybridization histochemistry was used to map the distribution of neurons
      expressing the substance P (SP) or neurokinin B (NKB) genes in the human
      hypothalamus and basal forebrain. Hypothalami from five adult males were frozen
      in isopentane at -30 degrees C and serially sectioned at 20 jm thickness. Every
      20th section was hybridized with [35S]-labeled, 48-base synthetic cDNA probes
      that were complementary to either SP or NKB mRNAs. Slides were dipped into
      nuclear emulsion for visualization of mRNAs at the single-cell level. The
      location of labeled neurons (greater than x 5 background) was mapped by using an
      image-combining computer microscope system. A distinct and complementary
      distribution pattern of SP and NKB neurons was observed in the human hypothalamus
      and basal forebrain. NKB was the predominant tachykinin in the rostral
      hypothalamus, whereas SP mRNA predominated in the posterior hypothalamus.
      Numerous NKB neurons were identified in the magnocellular basal forebrain, the
      bed nucleus of stria terminalis, and the anterior hypothalamic area. Scattered
      NKB neurons were present in the infundibular and paraventricular nuclei,
      paraolfactory gyrus, posterior hypothalamic area, lateral division of the medial
      mammillary nucleus, and amygdala. Numerous neurons expressing SP mRNAs were
      identified in the premammillary, supramammillary, and medial mammillary nuclei;
      the posterior hypothalamic area; and the corpus striatum. Scattered SP neurons
      were also observed in the preoptic area; the infundibular, intermediate,
      dorsomedial, and ventromedial nuclei; the infundibular stalk; the amygdala; the
      bed nucleus of stria terminalis; and the paraolfactory gyrus. These studies
      provide the first description of the location of neurons that express tachykinin
      gene transcripts in the human hypothalamus.

PMID- 9254038
TI  - Serotonergic axonal contacts on identified cat trigeminal motoneurons and their
      correlation with medullary raphe nucleus stimulation.
AB  - The innervation of the trigeminal motor nucleus by serotonergic fibers with cell
      bodies in the raphe nuclei pallidus and obscurus suggests that activation of this
      pathway may alter the excitability of trigeminal motoneurons. Thus, we recorded
      intracellular responses from cat jaw-closing (JC) andjaw-opening (JO) alpha
      motoneurons evoked by raphe stimulation and used a combination of intracellular
      staining of horseradish peroxidase (HRP) and immunohistochemistry at the light
      and electron microscopic levels to examine the distribution of contacts made by
      serotonin (5-HT)-immunoreactive boutons on the two motoneurons types. Electrical
      stimulation applied to the nucleus raphe pallidus-obscurus complex induced a
      monosynaptic excitatory postsynaptic potential (EPSP) in JC (masseter) alpha
      motoneurons and an EPSP with an action potential in JO (mylohyoid) alpha
      motoneurons. The EPSP rise-times (time to peak) and half widths were
      significantly longer in the JC than in the JO motoneurons. The EPSPs were
      suppressed by systemic administration of methysergide (2 mg/kg). Six JC and seven
      JO alpha-motoneurons were well stained with HRP. Contacts were seen between 5-HT
      immunoreactive boutons and the motoneurons. The JC motoneurons received a
      significantly larger number of the contacts than did the JO motoneurons. The
      contacts were distributed widely in the proximal three-fourths of the dendritic
      tree of JC motoneurons but were distributed on more proximal dendrites in the JO
      motoneurons. At the electron microscopic level, synaptic contacts made by 5-HT
      immunoreactive boutons on motoneurons were identified. The present study
      demonstrated that JC motoneurons receive stronger 5-HT innervation, and this
      correlates with the fact that raphe stimulation caused larger EPSPs among these
      neurons than among JO motoneurons.

PMID- 9254039
TI  - Insular cortex and neighboring fields in the cat: a redefinition based on
      cortical microarchitecture and connections with the thalamus.
AB  - The insular areas of the cerebral cortex in carnivores remain vaguely defined and
      fragmentarily characterized. We have examined the cortical microarchitecture and
      thalamic connections of the insular region in cats, as a part of a broader study
      aimed to clarify their subdivisions, functional affiliations, and eventual
      similarities with other mammals. We report that cortical areas, which resemble
      the insular fields of other mammals, are located in the cat's orbital gyrus and
      anterior rhinal sulcus. Our data suggest four such areas: (a) a "ventral
      agranular insular area" in the lower bank of the anterior rhinal sulcus,
      architectonically transitional between iso- and allocortex and sparsely connected
      to the thalamus, mainly with midline nuclei; (b) a "dorsal agranular insular
      area" in the upper bank of the anterior rhinal sulcus, linked to the mediodorsal,
      ventromedial, parafascicular and midline nuclei; (c) a "dysgranular insular area"
      in the anteroventral half of the orbital gyrus, characterized by its connections
      with gustatory and viscerosensory portions of the ventroposterior complex and
      with the ventrolateral nucleus; and (d) a "granular insular area", dorsocaudal in
      the orbital gyrus, which is chiefly bound to spinothalamic-recipient thalamic
      nuclei such as the posterior medial and the ventroposterior inferior. Three
      further fields are situated caudally to the insular areas. The anterior sylvian
      gyrus and dorsal lip of the pseudosylvian sulcus, which we designate "anterior
      sylvian area", is connected to the ventromedial, suprageniculate, and lateralis
      medialis nuclei. The fundus and ventral bank of the pseudosylvian sulcus, or
      "parainsular area", is associated with caudal portions of the medial geniculate
      complex. The rostral part of the ventral bank of the anterior ectosylvian sulcus,
      referred to as "ventral anterior ectosylvian area", is heavily interconnected
      with the lateral posterior-pulvinar complex and the ventromedial nucleus. Present
      results reveal that these areas interact with a wide array of sensory, motor, and
      limbic thalamic nuclei. In addition, these data provide a consistent basis for
      comparisons with cortical fields in other mammals.

PMID- 9254040
TI  - Response to the Glyco-Forum.

PMID- 9254041
TI  - Partial purification and substrate specificity of heparan sulfate alpha-N
      acetylglucosaminyltransferase I: synthesis, NMR spectroscopic characterization
      and in vitro assays of two aryl tetrasaccharides.
AB  - Studies of heparan sulfate biosynthesis on beta-D-xylosides have led to the
      hypothesis that heparan sulfate alpha-N-acetylglucosaminyltransferase I (alpha
      GlcNAc-TI) recognizes structures at the reducing end of the proteoglycan linkage
      tetrasaccharide. We report here the in vivo and in vitro testing of this
      hypothesis using four synthetic substrates, benzyl- and 2-naphthalenemethanyl
      beta-D-xylosides, and two proteoglycan linkage tetrasaccharides containing benzyl
      alcohol or naphthalmethanol aglycones, viz., GlcAbeta(1 --> 3)Gal beta(1 -->
      3)Gal beta(1 --> 4)Xyl beta-O-Bn (BNT) and GlcAbeta(1 --> 3)Gal beta(1 --> 3)Gal
      beta(1 --> 4)Xyl beta-O-NM (NMT). The aryl tetrasaccharides were chemically
      synthesized and the 1H and 13C resonances were assigned by two-dimensional NMR
      spectroscopy. The inter-residue spatial constraints, determined by the 2D NOESY
      data, revealed essentially identical conformations for the interglycosidic
      linkages and Xyl-O-CH2Ar linkages in both compounds. Interestingly, the aromatic
      rings in both tetrasaccharides undergo rapid internal rotation across the CH2-Ar
      bond. These tetrasaccharides were used to assay heparan sulfate alpha-GlcNAc-TI
      from homogenates of wild-type CHO cells. alpha-GlcNAc-TI was also purified
      approximately 900-fold from rat liver and assayed with BNT and NMT. At nearly all
      concentrations tested, alpha-GlcNAc-TI activity from both CHO cell homogenates
      and rat liver was greater with the NMT. When fed to CHO cells, benzyl-beta-D
      xyloside primed heparan sulfate poorly relative to 2-naphthalenemethanyl-beta-D
      xyloside. Thus, the in vitro enzyme activity is consistent with the in vivo
      priming data that suggests that alpha-GlcNAc-TI can directly recognize structure
      at the reducing end of the linkage tetrasaccharide. These studies provide an in
      vivo basis for the possible role of core protein sequences in the biosynthesis of
      specific glycosaminoglycans.

PMID- 9254042
TI  - Molecular dynamics simulations of the two disaccharides of hyaluronan in aqueous
      solution.
AB  - Hyaluronan is an unusually stiff polymer when in aqueous solution, which has
      important consequences for its biological function. Molecular dynamics
      simulations of hyaluronan disaccharides have been performed, with explicit
      inclusion of water, to determine the molecular basis of this stiffness, and to
      investigate the dynamics of the glycosidic linkages. Our simulations reveal that
      stable sets of hydrogen bonds frequently connect the neighboring residues of
      hyaluronan. Water caging around the glycosidic linkage was observed to increase
      the connectivity between sugars, and further constrain them. This, we propose,
      explains the unusual stiffness of polymeric hyaluronan. It would allow the
      polysaccharide to maintain local secondary structure, and occupy large solution
      domains consistent with the visco-elastic nature of hyaluronan. Simulations in
      water showed no significant changes on inclusion of the exoanomeric effect. This,
      we deduced, was due to hyaluronan disaccharides ordering first shell water
      molecules. In some cases these waters were observed to transiently induce
      conformational change, by breaking intramolecular hydrogen bonds.

PMID- 9254043
TI  - Developmental changes in carbohydrate antigens in embryonic rat lens.
AB  - The functions of glycosphingolipids, especially those containing the alpha
      galactosyl epitope, were investigated during the development and differentiation
      of rat lens. Glycosphingolipids in embryonic lens tissue were mainly composed of
      neolacto-series glycosphingolipids and sialic acid-containing ganglio-series
      gangliosides GM3 and GD3. These glycosphingolipids and gangliosides were widely
      expressed on cell membranes in the lens vesicle and the elongating lens fibers.
      In particular, the expression of neolacto-series glycosphingolipids with the
      alpha-galactosyl epitope was found to be associated with the differentiation and
      interaction of lens fibers. Glycoproteins with the alpha-galactosyl epitope was
      also involved in the elongation of lens fibers. The expression of the
      glycoproteins was highly specific in elongating lens fibers when these were
      examined in head sections obtained at various embryonic stages. Thus, the alpha
      galactosyl epitope on glycosphingolipids and glycoproteins appears to be
      associated with the differentiation and elongation of lens fibers in the rat.
      Evolution-related changes in the expression of carbohydrate antigens are also
      discussed in relation to the development and cell-to-cell interaction of lens
      fibers in mammals.

PMID- 9254044
TI  - Expression of a cDNA encoding the glucose trimming enzyme glucosidase II in CHO
      cells and molecular characterization of the enzyme deficiency in a mutant mouse
      lymphoma cell line.
AB  - Glucosidase II is an ER resident glycoprotein involved in the processing of N
      linked glycans and probably a component of the ER quality control of
      glycoproteins. For cloning of glucosidase II cDNA, degenerate oligonucleotides
      based on amino acid sequences derived from proteolytic fragments of purified pig
      liver glucosidase II were used. An unamplified cDNA library from pig liver was
      screened with a 760 bp glucosidase II specific cDNA fragment obtained by RT-PCR.
      A 3.9 kb glucosidase II cDNA with an open reading frame of about 2.9 kb was
      obtained. The glucosidase II sequence did not contain known ER retention signals
      nor hydrophobic regions which could represent a transmembrane domain; however, it
      contained a single N-glycosylation site close to the amino terminus. All studied
      pig and rat tissues exhibited an mRNA of approximately 4.4 kb with varying tissue
      expression levels. The authenticity of the identified cDNA with that coding for
      glucosidase II was proven by overexpression in CHO cells. Mouse lymphoma PHAR 2.7
      cells, deficient in glucosidase II activity, were shown to be devoid of
      transcripts.

PMID- 9254045
TI  - Mevalonate-regulated mechanisms in cell growth control: role of dolichyl
      phosphate in expression of the insulin-like growth factor-1 receptor (IGF-1R) in
      comparison to Ras prenylation and expression of c-myc.
AB  - One or more mevalonate derivatives of non-sterol type have been proposed to be of
      indispensable importance for cell growth. Conceivable mevalonate-dependent
      mechanisms involved in growth control are farnesylation of Ras proteins,
      regulation of c-myc expression, and N-linked glycosylation of the IGF-1 receptor.
      The latter mechanism might be rate-limited by dolichyl phosphate, which acts as a
      donor of oligosaccharides in glycoprotein synthesis in the endoplasmic reticulum.
      In order to study the significance for cell proliferation of the three
      aforementioned mevalonate-dependent processings, their inhibitory response due to
      mevalonate deprivation was explored and compared with the effect on DNA synthesis
      in the malignant melanoma cell line SK-MEL-2. We found that mevalonate depletion
      due to treatment with 3 microM lovastatin for 24 h, which efficiently growth
      arrested the cells, hardly at all affected the expression of c-myc, and although
      Ras prenylation was inhibited by 50%, the most pronounced effect of lovastatin
      was seen on N-linked glycosylation of IGF-1 receptors, which was inhibited by
      more than 95%. The order and magnitude of the decreased IGF-1 receptor
      glycosylation, which was followed by a decreased expression of IGF-1 receptors at
      the cell membrane, correlated well with the inhibition of DNA synthesis. We
      investigated whether dolichol, and in particular dolichyl phosphate, through its
      participation in N-linked glycosylation, act as regulators of IGF-1 receptor
      expression. First, we could confirm that exogenous dolichol became phosphorylated
      and in this form took part in the glycosylation processing. Secondly, we showed
      that dolichyl phosphate, in a dose-dependent manner, could increase the number of
      IGF-1 receptors at the cell membrane, simultaneously as DNA synthesis was
      stimulated. Taken together, our results provide direct evidence for an important
      role of dolichyl phosphate as a regulator of cell growth through limiting N
      linked glycosylation of the IGF-1 receptor.

PMID- 9254046
TI  - Microheterogeneity of the oligosaccharides carried by the recombinant bovine
      lactoferrin expressed in Mamestra brassicae cells.
AB  - The development of therapeutic glycoprotein production using the baculovirus
      expression system depends on the ability of insect cell lines to reproduce site
      specific mammalian-like N-glycans. A combination of 1H-NMR and mass spectrometry
      techniques (MALD-MS, ES-MS, and CID-MS-MS) allowed us to elucidate the N-linked
      oligosaccharides microheterogeneity on three different N-glycosylation sites,
      Asn233, Asn476, and Asn545, of a baculovirus-expressed recombinant bovine
      lactoferrin produced in Mamestra brassicae. Two families of N-glycan structures
      have been found: first, oligomannosidic glycans (Man[9-5]GlcNAc2) and secondly,
      short truncated partially fucosylated glycans (Man(3-2)[Fuc(0-1)]GlcNAc2). These
      results indicate that Mamestra brassicae cell line is not able to synthesize
      complex N-glycans, even if an alpha1,6-linked fucose residue is frequently
      present on the asparagine-bound N-acetylglucosamine residue of short truncated
      structures. Nevertheless, we have shown that Mamestra brassicae ensures the same
      N-glycosylation pattern as found on natural bovine lactoferrin showing the same
      distribution between complex and high-mannose type glycans on the different
      glycosylation sites. Sites which are naturally occupied by high-mannose glycans
      (Asn233 and Asn545) are substituted essentially by the same type of N-glycans in
      the recombinant counterpart, and the site Asn476,which carries sialylated complex
      type chains in the natural glycoprotein, is substituted by short, truncated,
      partially fucosylated chains in Mamestra brassicae-expressed bovine lactoferrin.
      These various results lead us to the conclusion that bovine lactoferrin is an
      interesting model to determine the potential of glycosylation of the
      baculovirus/insect cell expression systems.

PMID- 9254047
TI  - Structural characterization of glycophingolipids from the eggs of Schistosoma
      mansoni and Schistosoma japonicum.
AB  - The granulomatous pathology in human intestinal schistosomiasis is induced
      primarily by the egg antigens of schistosome, a parasitic trematode. Glycolipids
      and glycoproteins were extracted from the eggs of the two major species which
      infect human, Schistosoma mansoni and Schistosoma japonicum, for structural
      characterization based on highly sensitive mass spectrometric analysis coupled
      with chemical derivatization. Here, we demonstrate that a series of uniquely
      multifucosylated glycosphingolipids constitute the major egg glycolipids of S.
      mansoni but not of S. japonicum. The S. mansoni glycosphingolipids were found to
      be extended by varying numbers of an unusual repeating unit, -->4(Fuc1-->2Fuc1-
      >3)GlcNAc1-->, and terminating as +/-Fuc1-->2Fuc1-->3GalNAc1--> at the
      nonreducing terminus. The similarity of these fucosylated structures,
      particularly the nonreducing terminal sequence, to the previously identified
      multifucosylated O-linked oligosaccharides of the cercarial glycocalyx, suggests
      that they may constitute the cross-reacting epitopes between the egg antigens and
      cercariae of S. mansoni. On the other hand, the difucosylated GalNAc terminal
      epitope was not found on the glycosphingolipids of S. japonicum. Thus, it
      qualifies for a possible role as a species-specific recognition glycan.

PMID- 9254049
TI  - The N-glycosylation sites of soybean seed coat peroxidase.
AB  - Tryptic digestion of apo-soybean peroxidase (apo-SBP), with and without
      acetamidation, chromatographic separation of the tryptic fragments and MALDI-TOF
      analysis of the major components, both before and after digestion with
      glycopeptidase A, demonstrated the presence of six carbohydrate groups on five
      peptides. Five of the glycopeptides can be mapped with confidence to the peptides
      containing Asn16, Asn90, Asn104, Asn169, and Asn174. The sixth N-glycosylation
      site is not known and does not appear to be Asn145. It may be present on the N
      terminus of SBP, which has not been sequenced.

PMID- 9254048
TI  - Structural mapping of the glycans from the egg glycoproteins of Schistosoma
      mansoni and Schistosoma japonicum: identification of novel core structures and
      terminal sequences.
AB  - The structural diversity of the glycans from Schistosoma mansoni and Schistosoma
      japonicum egg glycoproteins was investigated using high sensitivity fast atom
      bombardment mass spectrometric screening of glycan pools released enzymically or
      chemically from egg extracts. The egg glycoproteins from the two species carry a
      comparable range of high mannose and complex type N-glycans with both lacNAc and
      lacdiNAc constituting the backbones of the antennae in the latter class.
      Truncated N-glycans similar to those found on nematodes, insects, and plants were
      also identified. Sequential digestion with peptide N-glycosidase F and peptide N
      glycosidase A afforded effective release and separation of N-glycans with
      nonfucosylated or alpha6-monofucosylated trimannosyl N,N'-diacetyl-chitobiose
      cores from those carrying core alpha3-, alpha6-difucosylation, all of which were
      found to be present in both species. Remarkably, a portion of the N-glycans from
      S. mansoni eggs was shown to be based on a xylosylated, alpha6-fucosylated
      trimannosyl core, whereas a portion of those from S. japonicum contains a
      xylosylated alpha3-, alpha6-difucosylated core which has not been previously
      described in any organism. O-Glycans were chemically released from the de-N
      glycosylated glycopeptides and found to carry terminal sequences similar to those
      in the N-glycans. This study provides further evidence that multi-fucosylated
      terminal HexNAc units, previously identified on the cercarial glycocalyx O
      glycans and egg glycosphingolipids, and now on the egg N- and O-glycans, are
      unique features of S. mansoni glycans. These multifucosylated terminal
      structures, which were not detected on the egg glycans of S. japonicum, are
      likely to constitute the cross-reacting epitopes between the eggs and cercariae
      of S. mansoni. Interestingly other HexNAc termini, including an unusual stretch
      of HexNAc3, were found to be common to both species. The mapping studies reported
      in this article provide an important foundation for further structural work in
      this challenging and important area of glycobiology.

PMID- 9254051
TI  - Purification and characterization of the Escherichia coli K1 neuB gene product N
      acetylneuraminic acid synthetase.
AB  - Escherichia coli K1 produces a capsular polysaccharide of alpha(2-8) poly-N
      acetylneuraminic acid. This polysaccharide is an essential virulence factor of
      these neuropathogenic bacteria. The genes necessary for the synthesis of neuNAc
      were localized to a plasmid containing the neuBAC genes of the K1 gene cluster.
      Cells harboring the neuB+ allele in an aldolase (nanA-) negative background
      produce neuNAc in vivo. Enzymatic synthesis of neuNAc could be demonstrated in
      extracts of cells harboring an expression plasmid (pNEUB) containing the neuB
      gene alone. NeuNAc synthetase was purified to homogeneity from extracts of cells
      harboring pNEUB. The molecular weight of the purified enzyme is 40 kDa, similar
      to that predicted by the nucleotide sequence of the neuB gene. The amino terminal
      sequence of the purified protein matches that predicted by the nucleotide
      sequence of the neuB gene. NeuNAc synthetase catalyzes the formation of neuNAc as
      indicated by its coupling to the CMP-neuNAc synthetase reaction. The enzyme
      condenses manNAc and PEP with the release of phosphate. The E. coli neuNAc
      synthetase is specific for manNAc and PEP, unlike rat liver enzyme that utilizes
      N-acetylmannosamine-6-phosphate to form neuNAc-9-PO4. This represents the first
      report of a purification of a sialic acid synthetase from either a eukaryotic or
      prokaryotic source to homogeneity. These experiments clearly demonstrate an
      aldolase-independent sialic acid synthetase activity in E. coli K1.

PMID- 9254050
TI  - Leishmania adleri, a lizard parasite, expresses structurally similar
      glycoinositolphospholipids to mammalian Leishmania.
AB  - Glycoinositolphospholipids (GIPLs) were isolated from promastigotes of the lizard
      parasites Leishmania adleri by phenol/water extraction. Phosphoinositol
      oligosaccharides were liberated by mild alkaline hydrolysis, purified by gel
      filtration and high pH anion exchange chromatography, and characterized by
      methylation analysis, fast atom bombardment mass spectrometry, and nuclear
      magnetic resonance spectroscopy. The four major compounds (I-IV) from L. adleri
      were linked to alkylacyl glycerol, and their glycan moieties had the following
      structures: Man alpha(1-2)Man alpha(1-6)[Man alpha(1-3)] Man alpha(1-4)GlcN
      alpha(1-6)Ins-1-PO4 (I), Galp alpha(1-6) Galp alpha(1-3)Galf beta(1-3)Man alpha(1
      3)Man alpha(1-4)GlcN alpha(1-6)Ins-1-PO4 (II), Galp alpha(1-3)Galf beta(1-3)Man
      alpha(1-3) Man alpha(1-4)GlcN alpha(1-6)Ins-1-PO4 (III), Man alpha(1-2)[EtNP(
      6)]Man alpha(1-6)[Man alpha(1-3)] Man alpha(1-4)GlcN alpha(1-6)Ins-1-PO4 (IV).
      These compounds are analogous to the previously characterized GIPLs from New and
      Old World leishmanial parasites of mammals designated iM4 (identical to compound
      I), GIPLs 3 and 2 (identical to compounds II and III, respectively), and EPiM4
      (identical to compound IV), which is consistent with a close phylogenetic
      relationship between lizard and mammalian Leishmania. However, in contrast to the
      mammalian parasites, the abundant surface glycoconjugate known as
      lipophosphoglycan was either absent or confined to the flagellar pocket region in
      L. adleri.

PMID- 9254052
TI  - Oxidized low density lipoproteins stimulate galactosyltransferase activity, ras
      activation, p44 mitogen activated protein kinase and c-fos expression in aortic
      smooth muscle cells.
AB  - Previously, our laboratory has shown that oxidized low density lipoproteins (Ox
      LDL) can exert a concentration-dependent stimulation in the proliferation of
      aortic smooth muscle cells, "a hallmark in the pathogenesis of atherosclerosis"
      (Chatterjee, S. (1992) Mol. Cell. Biochem., 111, 143-147). Here we report a novel
      aspect of Ox-LDL-mediated signal transduction. We demonstrate that in aortic
      smooth muscle cells, Ox-LDL stimulates the activity of a UDP
      galactose:glucosylceramide beta1-->4 galactosyltransferase (GalT-2) and
      phosphorylation/activation of p44 mitogen-activated protein (MAP) kinase (p44
      MAPK). The activity of GalT-2 increased about 2-fold within 2.5-5 min of
      incubation of cells with Ox-LDL (10 microg/ml). After 5 min of incubation of
      cells with Ox-LDL, but not LDL, there was a 2-fold increase in the activity of
      p44 MAPK. Phosphoamino acid analysis employing thin layer chromatography revealed
      that the tyrosine and threonine moieties of p44 MAPK was phosphorylated by Ox
      LDL. D-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP; a potent
      inhibitor of GalT-2) impaired the Ox-LDL mediated induction of p44 MAPK activity
      and the phosphorylation of tyrosine and threonine residues in p44 MAPK. This
      phenomenon was bypassed by the simultaneous addition of lactosylceramide. The
      upstream and downstream parameters in MAP kinase signaling pathways were
      investigated next. We found that Ox-LDL stimulated (9-fold) the loading of GTP on
      Ras. Interestingly, Ox-LDL specifically induced c-fos mRNA expression (6.5-fold)
      in these cells, as compared to the control. Thus, one of the biochemical
      mechanisms in Ox-LDL mediated induction in the proliferation in aortic smooth
      muscle cells may involve GalT-2 activation, lactosylceramide production, Ras GTP
      loading, activation of the kinase cascade, and c-fos expression.

PMID- 9254053
TI  - Enzymatic transfer of a beta1,6-linked N-acetylglucosamine to the alpha-galactose
      of globo-N-tetraose: in vitro synthesis of a novel hybrid pentasaccharide of
      lacto-globo type.
AB  - A novel saccharide was synthesized by incubating globo-N-tetraose, GalNAc beta1
      3Gal alpha1-4Gal beta1-4Glc, and UDP[3H]GlcNAc with hog gastric mucosal
      microsomes, known to contain beta1,6-N-acetylglucosaminyltransferase activity of
      a broad acceptor specificity. Chromatography and MALDI-TOF mass spectrometry of
      the product, as well as the amount of incorporated radioactivity indicated that
      one [3H]GlcNAc residue was transferred to the acceptor saccharide. One- and two
      dimensional 1H NMR-spectroscopic analysis of the product and ESI-CID mass
      spectrometry of the pentasaccharide in permethylated form established its
      structure as GalNAc beta1-3([3H]GlcNAc beta1-6)Gal alpha1-4Gal beta1-4Glc. The
      new enzyme activity possesses substrate specificity features common to a purified
      beta1,6-GlcNAc-transferase from bovine tracheal epithelium, which forms branches
      at the subterminal beta1,3-substituted galactose and accepts both GlcNAc- and Gal
      configuration at the terminal residue of the acceptor (Ropp et al. (1991) J.
      Biol. Chem., 266, 23863-23871). The new beta1,6-GlcNAc-branch was readily
      galactosylated by bovine milk beta1,4-galactosyltransferase, revealing a pathway
      to novel hybrid type glycans with N-acetyllactosamine chains on globotype
      saccharides. This pathway may lead to the rare IP blood-group antigen and to
      globoside-like molecules mediating cell adhesion.

PMID- 9254054
TI  - Application of matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry with delayed ion extraction to ganglioside analyses.
AB  - Various monosialo- and disialo-gangliosides and their derivatives were examined
      by delayed ion extraction matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (DE MALDI-TOF MS) in the reflector mode with alpha-cyano
      4-hydroxycinnamic acid or 2,5-dihydroxybenzoic acid used as the matrix. Native
      gangliosides were generally found to give good spectra in the negative ion mode.
      2,5-Dihydroxybenzoic acid was a better matrix for gangliosides than alpha-cyano-4
      hydroxycinnamic acid, because this matrix seemed to minimize loss of sialic acid
      and carbon dioxide of gangliosides. About 1 pmol of ganglioside was able to be
      detected with this matrix. When "A-series" gangliosides such as GD1a and GalNAc
      GD1a gave undesirable extra peaks probably due to loss of sialic acid besides
      molecule-related ion peaks, the methyl-esterification of the gangliosides at the
      carboxyl groups of sialic acids was found to be necessary to obtain good DE MALDI
      TOF mass spectra in the positive ion mode. In contrast, "B-series" gangliosides
      such as GD1b, GD2, and GD3 gave rise to major dehydrated molecule-related ion [M
      H2O-H]- peaks in the negative ion mode without the pretreatment of methyl
      esterification. The DE MALDI-TOF mass spectrometric analysis enabled us to
      distinguish between GD1a and GD1b, which have the same molecular weight. It was
      also found that not only a purified sample, but also a mixed sample of various
      gangliosides was amenable to the identification of them by DE MALDI-TOF MS.

PMID- 9254055
TI  - Obesity in db and ob animals leads to impaired hepatic very low density
      lipoprotein secretion and differential secretion of apolipoprotein B-48 and B
      100.
AB  - Dyslipidemia secondary to obesity is commonly observed in both animals and
      humans. As it has been hypothesized that obesity can result in overproduction of
      VLDL, leading to the subsequent dyslipidemia, we have examined the triglyceride
      and apoB secretion rates in vivo in obese C57BI/ KsJ db/db and C57BI/6J ob/ob
      mice and their lean littermates. In ob/ob animals, obesity resulted in
      significantly lower, not higher, triglyceride secretion rates in both males (3.94
      +/- 0.49 mg/h per g liver vs. 5.45 +/- 0.29 mg/h per g liver in lean littermates,
      P < 0.001) and females (4.29 +/- 0.81 mg/h per g liver vs. 5.25 +/- 0.59 mg/h/g
      liver, P < 0.001). For db/db, the obese females did not show a statistically
      significant triglyceride secretion rate compared to their lean littermates. Only
      the male db/db animals showed a significantly higher triglyceride secretion rate
      compared with lean littermates (5.50 +/- 1.1 mg/h per g liver vs. 3.37 +/- 0.36
      mg/h/g liver, P < 0.001). Examination of the apolipoprotein B (apoB) secretion
      rates showed that for ob/ob animals and db/db obese females, apoB48 secretion was
      significantly decreased compared to that of normal littermates, with a small
      increase in apoB-100 secretion. Total apoB secreted, however, was not increased.
      Our data further suggest that the predominant cause of the dyslipidemia under
      these conditions is a defect in removal of VLDL from the circulation.

PMID- 9254056
TI  - Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR
      BI, an HDL receptor that mediates selective lipid uptake.
AB  - The class B type I scavenger receptor, SR-BI, binds HDL, mediates selective
      uptake of HDL cholesteryl esters by cultured cells, and its expression is
      coordinately regulated with steroidogenesis in several endocrine tissues
      (adrenal, ovary, testes). SR-BI can also bind LDL and anionic phospholipids,
      which raised the possibility that HDL apolipoproteins might not participate
      directly in HDL binding. We have examined the ability of individual human HDL
      apolipoproteins (apoA-I, apoA-II, and apoC-III) reconstituted into
      phospholipid/unesterified cholesterol complexes to bind to murine SR-BI (mSR-BI)
      expressed in stably transfected cultured cells. All three
      apolipoprotein/phospholipid/unesterified cholesterol complexes specifically
      associated with mSR-BI expressing cells with high affinity and competed for the
      binding of HDL, while apolipoprotein-free complexes did not. Furthermore, lipid
      free forms of these soluble apolipoproteins also competed for HDL and
      apolipoprotein/ phospholipid/cholesterol complex association with mSR-BI, but
      locust high density lipophorin and bovine serum albumin were not effective
      competitors.Thus, all three of the HDL apolipoproteins (apoA-I, apoA-II, and apoC
      III) tested can directly mediate binding to mSR-BI, and this multiligand
      apolipoprotein receptor may be responsible for at least some of the
      multilipoprotein and apolipoprotein binding activity previously observed in cells
      and tissues.

PMID- 9254057
TI  - Effects of simvastatin on the metabolism of polyunsaturated fatty acids and on
      glycerolipid, cholesterol, and de novo lipid synthesis in THP-1 cells.
AB  - In the monocytic THP-1 cells, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitor simvastatin (5 microM) enhances the conversion of exogenous
      linoleic (18:2 n-6) and eicosapentaenoic (20:5 n-3) acids to their long-chain
      polyunsaturated fatty acid (LC-PUFA) derivatives, and this effect is associated
      with changes in the desaturation steps. In addition, formation of monounsaturated
      fatty acids from endogenously synthesized precursors is increased. These
      metabolic changes lead to elevated LC-PUFA and fatty acid (FA) unsaturation in
      cells. The effects of simvastatin on FA metabolism are associated with increased
      synthesis of triglycerides from glycerol. The dose-effect relationships for the
      activity of simvastatin on total linoleic acid (LA) conversion and cholesterol
      synthesis reveal that enhancement of PUFA metabolism is already maximal at 0.5
      microM simvastatin, whereas cholesterol synthesis is further inhibited by
      concentrations of simvastatin up to 5 microM. The effects of 5 microM simvastatin
      on PUFA metabolism are partially prevented by mevalonate (1 mM) and
      geranylgeraniol (5 microM) but not by farnesol (10 microM). These data indicate
      that HMG-CoA inhibitors have profound effects on PUFA metabolism, and that the
      pathways for cholesterol and PUFA synthesis are mutually modulated.

PMID- 9254058
TI  - Estrogen dependence of synthesis and secretion of apolipoprotein B-containing
      lipoproteins in the chicken hepatoma cell line, LMH-2A.
AB  - The chicken hepatoma cell line LMH-2A, which permanently overexpresses the
      chicken estrogen receptor, was used to study the synthesis and secretion of
      lipoproteins in response to treatment with estrogen. In the absence of the
      hormone, only small amounts of apolipoprotein B (apoB) and no apolipoprotein VLDL
      II (apoII) were found in cell extracts. After treatment of cells with moxestrol,
      a stable estrogen derivative, for 24 to 48 h, a dramatic increase in the
      quantities of these lipoproteins was observed both in cell extracts and in the
      medium. As determined by pulse-chase experiments, both proteins also showed
      enhanced rates of synthesis after estrogen induction, and secretion of the newly
      synthesized proteins was essentially complete by 6 h. The secreted apoB
      containing lipoprotein particles have a density corresponding to that of very low
      density lipoprotein (VLDL). Furthermore, in estrogen-stimulated cells, the
      secreted particles also contain apoII, as shown by co-immunoprecipitation of
      apoII, and apoB. It appears that vitellogenin, the product of another estrogen
      regulated gene in egg-laying species, is not synthesized by LMH-2A cells. Taken
      together, the data suggest that LMH-2A cells provide a new and promising cell
      system to investigate lipoprotein synthesis, assembly, and secretion in an
      estrogen-dependent manner.

PMID- 9254059
TI  - Uptake of hypertriglyceridemic very low density lipoproteins and their remnants
      by HepG2 cells: the role of lipoprotein lipase, hepatic triglyceride lipase, and
      cell surface proteoglycans.
AB  - Hypertriglyceridemic very low density lipoproteins (HTG-VLDL, S(f) 60-400) are
      not taken up by HepG2 cells. However, addition of bovine milk lipoprotein lipase
      (LPL) at physiological concentrations markedly stimulates uptake. In the present
      study, we determined whether: a) LPL catalytic activity is required for uptake,
      b) LPL functions as a ligand, and c) cell surface hepatic triglyceride lipase
      (HL) and/or proteoglycans are involved. Incubation of HepG2 cells with HTG-VLDL
      plus LPL (8 ng/ml) increased cellular cholesteryl ester (CE) 3.5-fold and
      triglyceride (TG) 6-fold. Heat-inactivation of LPL abolished the effect. Addition
      of tetrahydrolipstatin (THL, an LPL active-site inhibitor) to HTG-VLDL + LPL,
      inhibited the cellular increase in both CE and TG by greater than 90%. Co
      incubation of HTG-VLDL + LPL with heparin, heparinase, or heparitinase, blocked
      CE accumulation by 70%, 48%, and 95%, respectively, but had no effect on the
      increase in cellular TG. Pre-treatment of cells with 1 mM 4-methylumbelliferyl
      beta-D-xyloside, (beta-xyloside) to reduce cell surface proteoglycans inhibited
      the increase in CE induced by HTG-VLDL + LPL by 78%. HTG-VLDL remnants, prepared
      in vitro and isolated free of LPL activity, stimulated HepG2 cell CE 2.8-fold in
      the absence of added LPL, a process inhibited with THL by 66%. Addition of LPL (8
      ng/ml) to remnants did not further enhance CE accumulation. HepG2 cell HL
      activity, released by heparin, was inhibited 95% by THL. The amount of HL
      activity and immunoreactive mass, released by heparin, was reduced 50-60% in beta
      xyloside-treated cells. These results indicate that physiological concentrations
      of LPL promote HepG2 cell uptake of HTG-VLDL primarily due to remnant formation
      and that LPL does not play a major role as a ligand. HL activity and cell surface
      proteoglycans significantly enhance the subsequent uptake of VLDL remnants.

PMID- 9254060
TI  - Characterization of a specific polyclonal antibody against 13
      hydroperoxyoctadecadienoic acid-modified protein: formation of lipid
      hydroperoxide-modified apoB-100 in oxidized LDL.
AB  - Lipid hydroperoxide may react with protein or amino phospholipid without
      secondary decomposition. We prepared a polyclonal antibody to lipid hydroperoxide
      modified proteins using 13S-hydroperoxy-9Z, 11E-octadecadienoic acid-modified
      keyhole limpet hemocyanin (13-HPODE-KLH) as immunogen. The antibody recognized 13
      HPODE-modified bovine serum albumin (BSA), but not aldehyde-modified proteins,
      such as malondialdehyde-modified BSA. The antibody also recognized adducts
      derived from 13-HPODE and 13S-hydroperoxy-9Z, 11E, 15Z-octadecatrienoic acid (13
      HPOTRE(alpha)). The oxidized alpha-linolenic acid- and linoleate-protein adducts
      were recognized by the antibody. Oxidized phospholipid-protein adducts were
      scarcely recognized by the antibody. However, when ester bonds of phospholipids
      containing linoleic acid were hydrolyzed by alkaline treatment, the cross
      reactivities appeared. The result suggests that a phospholipid hydroperoxide can
      react with a protein directly or indirectly, and a carboxyl terminal (COOH) of
      the lipid in an adduct was needed as an epitope. Oxidized LDL (ox-LDL) was
      prepared by the incubation of LDL with copper ion or 2,2'-azobis(2
      amidinopropane)dihydrochloride (AAPH), and the formation of lipid hydroperoxide
      modified apolipoprotein was confirmed using the antibody. A slight
      immunoreactivity was observed in ox-LDL without alkaline treatment. When the ox
      LDL was treated with alkali to hydrolyze the ester bonds of the lipid, enhanced
      antigenicity appeared with time-dependency. The results suggest that lipid
      hydroperoxide-modified apolipoprotein was formed during the oxidation of LDL.

PMID- 9254061
TI  - Oxidation products of cholesteryl linoleate are resistant to hydrolysis in
      macrophages, form complexes with proteins, and are present in human
      atherosclerotic lesions.
AB  - Accumulation of the insoluble lipid-protein complex, ceroid, is a characteristic
      of atherosclerotic plaques. To determine whether deficient processing of
      cholesteryl esters in oxidized (ox) low density lipoprotein (LDL) contributes to
      ceroid formation, we studied the hydrolysis of internalized [3H] cholesteryl
      linoleate (CL) in oxLDL by mouse peritoneal macrophages (MPM). The hydrolysis by
      MPM of [3H]CL incorporated into oxLDL or LDL did not differ, suggesting that
      products of lipid and/or apoB oxidation had no impact on the lysosomal hydrolysis
      of [3H]CL. To evaluate the hydrolysis of oxCL by MPM, we subjected extensively
      ox[3H]CL to fractionation by TLC. The predominant fraction (D) consisted of
      sterols and oxysterols esterified to scission products of oxidized fatty acids
      containing terminal carbonyl groups, i.e., lipid core aldehydes. The extent of
      hydrolysis of [3H]-fraction D by MPM cultures, as well as by MPM extracts at pH
      4.0, was significantly reduced when compared to the hydrolysis of intact [3H]CL.
      Fraction D also formed complexes with serum proteins, and the purified core
      aldehyde, cholesteryl 9-oxononanoate reacted with epsilon-amino group of lysines.
      Finally, several cholesteryl ester aldehydes were detected in lipid extracts of
      human atheroma. These results suggest that decomposition products of extensively
      oxidized cholesteryl linoleate that are also present in atherosclerotic lesions,
      are not adequately degraded by mouse peritoneal macrophage lysosomes and could
      interact with proteins to form ceroid.

PMID- 9254063
TI  - Metabolism of all-trans-retinoic acid by cultured human epidermal keratinocytes.
AB  - The uptake and metabolism of exogenous all-trans-retinoic acid by human epidermal
      keratinocytes in submerged culture was examined. Retinoic acid presented to
      keratinocytes in physiological form bound to albumin was rapidly taken up. Peak
      cellular concentrations were achieved within 1 h and were 50- to 100-fold higher
      than that in medium. Retinoic acid metabolism was less rapid but was vigorous,
      exhibiting a half-life of 6 h. Neither uptake nor metabolism was saturable at
      medium retinoic acid concentrations up to 1 microM. Eighty-five percent of
      retinoic acid was metabolized to unidentified polar compounds which were excreted
      from cells to the medium. The production and clearance of the polar metabolites
      was inhibited 60% by 10 microM ketoconazole. Fifteen percent of intracellular
      retinoic acid was converted to 3,4-didehydroretinoic acid, was proportional to
      cellular retinoic acid concentration, and was not affected by ketoconazole.
      Cellular retinyl ester content, which is sensitive to exogenous retinoic acid,
      was correlated with both the concentration and the quantity, of retinoic acid in
      the culture system. These results suggest that the metabolism of retinoic acid in
      keratinocytes is substrate limited and has potential to limit the availability of
      exogenous retinoic acid for retinoid signaling.

PMID- 9254062
TI  - Association of genetic variations in apolipoprotein B with hypercholesterolemia,
      coronary artery disease, and receptor binding of low density lipoproteins.
AB  - To search for unique mutations in the apolipoprotein B (apoB) gene that disrupt
      the binding of LDL to its receptor and cause hypercholesterolemia, we examined
      more than 800 patients with high LDL cholesterol levels and/or coronary artery
      disease (CAD). Analysis of patient DNA by single-strand conformation polymorphism
      and allele-specific oligonucleotide hybridization of the sequence surrounding the
      putative receptor- binding domain of apoB (amino acid positions 2965 to 3534)
      revealed seven variations. LDL from heterozygotes with either Arg 3500 Gln or Arg
      3531 Cys bound defectively with the LDL receptor in competitive binding assays.
      The Arg 3500 Gln substitution was statistically more prevalent in patients with
      hypercholesterolemia (P = 0.0003). Total cholesterol and LDL-cholesterol were
      significantly higher (P< 0.0004) in 34 apoB 3500 Gln carriers than in the
      controls. The allele encoding the Arg 3531 Cys substitution was more prevalent
      (0.8%) in the CAD group (P = 0.05) than in the controls. A Ser 3252 Gly variant
      was statistically more prevalent in the hypercholesterolemic group (P = 0.03),
      but LDL with this mutation had normal LDL receptor-binding activity. The other
      four variants identified (Leu 3350 Leu, Gln 3405 Glu, Val 3396 Met, and Ser 3455
      Arg) were not associated with defective LDL-receptor binding,
      hypercholesterolemia, or CAD, nor were the apoB mutations associated with
      elevated lipid levels in family members. The surprising result that only two
      mutations of apoB in the receptor-binding domain (Arg 3500 Gln and Arg 3531 Cys)
      were associated with defective LDL binding, hypercholesterolemia, or CAD is in
      stark contrast with familial hypercholesterolemia, where nearly 150 mutations of
      the LDL receptor have been described that disrupt its function. This study
      strongly suggests that a limited number of mutations of apoB markedly influence
      LDL binding to its receptor.

PMID- 9254064
TI  - Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in
      neonatal rat ventricular myocytes.
AB  - The energy need of cardiac muscle cells in vivo is largely covered by the
      oxidation of saturated and mono-unsaturated fatty acids (FA). However, in vitro
      studies have shown that the saturated FA C16:0 at physiological concentrations
      exerts detrimental effects on primary cultures of neonatal rat ventricular
      myocytes by, as yet, unknown mechanisms. To evaluate the noxious effects of FA in
      more detail, neonatal cardiomyocytes were exposed to saturated (C16:0; C18:0) or
      mono-unsaturated (C16:1; cis-C18:1; trans-C18:1) FA, or combinations thereof for
      up to 48 h. FA (0.5 mM) complexed to bovine serum albumin (BSA) (0.15 mM) were
      added to a glucose-containing defined medium. Irrespective of the length and
      degree of unsaturation of the aliphatic chain, FA supplied to the cells were
      readily incorporated in the phospholipid pool. In the presence of mono
      unsaturated FA, cardiomyocytes remained healthy and accumulated substantial
      amounts of triacylglycerol. In contrast, within 24 h after application of the
      saturated FA C16:0 or C18:0, cells had become irreversibly damaged, as evidenced
      by the presence of pyknotic nuclei and massive release of the cytosolic markers
      lactate dehydrogenase (LDH) and fatty acid-binding protein (FABP). Moreover, the
      occurrence of DNA-laddering indicated that apoptosis was involved. Induction of
      apoptotic cell death by C16:0 was counteracted by the co-administration of
      equimolar amounts of cis-C18:1, whereas trans-C18:1 delayed, but did not prevent,
      loss of cardiomyocyte viability. The present findings suggest that the
      incorporation of saturated, but not mono-unsaturated, fatty acids induces
      alterations in the phospholipid membrane, which initiate apoptotic cell death in
      neonatal cardiomyocytes.

PMID- 9254065
TI  - Phenotypic characterization of Lith genes that determine susceptibility to
      cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder
      bile.
AB  - Lith genes control susceptibility to cholesterol gallstone formation in inbred
      strains of mice on a lithogenic diet containing high fat, high cholesterol and
      0.5% cholic acid. Our study defines the physical-chemical phenotypes of C57L,
      AKR, and (C57L x AKR) F1 mouse gallbladder biles during 56 days on the lithogenic
      diet. We found enhanced cholesterol supersaturation, accumulation of mucin gel,
      and larger gallbladders in all C57L and F1 mice, as well as more frequent
      gallstone formation in male C57L and F1 mice (80%) compared to females (40%) or
      AKR mice (15%). In male C57L and F1 mice, mucin gel accumulated at 3 days,
      followed by cholesterol supersaturation and phase separation of liquid crystals,
      solid monohydrate crystals, and, in 43% of mice, anhydrous cholesterol crystals;
      whereas, in females, phase separations were delayed 2 to 9 days, and anhydrous
      crystals did not form. In AKR mice, cholesterol supersaturation and phase
      separations were infrequent and delayed, and gender did not influence the
      phenotype. Taurocholate invariably replaced endogenous bile salts, especially
      tauro-beta-muricholate, with crystallization sequences matching taurocholate
      containing model bile systems. We conclude: i) Lith genes determine biliary
      cholesterol supersaturation, mucin gel accumulation, gallbladder size, phase
      separation, and prevalence of cholesterol gallstones. ii) Identical phenotypes in
      C57L and F1 mice indicate susceptibility to cholesterol gallstones is genetically
      dominant, favoring males 2:1. iii) Mucin gel accumulation, crystallization, and
      stone formation are rare in AKR mice. This definition of the physical chemistry
      of lithogenesis should aid in further elucidation of the Lith genes and the
      proteins they encode.

PMID- 9254066
TI  - Ganglioside hydration study by 2H-NMR: dependence on temperature and water/lipid
      ratio.
AB  - Dynamic properties of 2H2O in samples of ganglioside aggregates hydrated at
      water/lipid ratios ranging from 25:1 to 8000:1 mole/mole were studied by using
      deuterium nuclear magnetic resonance (2H-NMR). We present a physical model for
      the interpretation of the measured spin-spin relaxation times (T2). For all the
      concentrations studied the model provides evidence for the existence of at least
      two kinds of water environments: one in which the rotational correlation time is
      in the range of 10(-9) to 10(-8) s, and a second in which it lies between 10(-11)
      to 10(-10) s. A detailed study on the temperature dependence was performed for
      two of the concentrations, one corresponding to the hexagonal phase (100:1
      mole/mole) and the other involving a micellar phase (200:1 mole/mole). In the
      100:1 2H2O/ganglioside molar ratio sample, most of the water is tightly bound to
      long cylindrical structures. For the 200: 1 sample, there are on average
      approximately 30 water molecules tightly bound to the polar head group of each
      ganglioside molecule. The relative number and dynamics of molecules in this
      environment are essentially insensitive to temperature variations in the range
      220-300K The rest of water molecules are also influenced by the aggregate, having
      a different mobility from that observed in the free liquid state.

PMID- 9254067
TI  - Plasma lipoprotein distribution of apoC-III in normolipidemic and
      hypertriglyceridemic subjects: comparison of the apoC-III to apoE ratio in
      different lipoprotein fractions.
AB  - In order to assess the relationship between plasma accumulation of triglyceride
      rich lipoproteins (TRL) and lipoprotein levels of apoC-III and apoE, we have
      measured apoC-III and apoE in lipoproteins separated according to size (by
      automated gel filtration chromatography) from plasma of normolipidemic subjects
      (plasma triglyceride (TG): 0.84 +/- 0.10 mmol/l; mean +/- SE, n = 8), and from
      type III (n = 8) and type IV (n = 8) hyperlipoproteinemic patients, matched for
      plasma TG (5.76 +/- 0.62 v 5.55 +/- 0.45 mmol/l, resp.). Total plasma apoC-III
      concentration was similar in type III and type IV patients (33.1 +/- 3.4 v 37.6
      +/- 4.4 mg/dl, respectively), but was significantly increased compared to
      normolipidemic controls (10.0 +/- 1.0 mg/dl, P < 0.001). TRL apoC-III was lower
      and high density lipoprotein (HDL) apoC-III was significantly higher in type III
      versus type IV subjects (14.8 +/- 3.2 vs. 22.8 +/- 3.0 mg/dl, P < 0.05; 8.3 +/-
      1.0 vs. 5.2 +/- 0.5 mg/dl, P < 0.05). Plasma concentration of apoC-III in
      lipoproteins that eluted between TRL and HDL (intermediate-sized lipoproteins,
      ISL) was similar in the two hypertriglyceridemic groups (10.1 +/- 1.3 vs. 9.7 +/-
      1.6 mg/dl), but was significantly higher (P< 0.05) than controls (2.2 +/- 0.3
      mg/dl). TRL, ISL, and HDL apoE concentrations were significantly higher in type
      III versus type IV subjects (P < 0.05). All lipoprotein fractions in type III
      patients were characterized by lower apoC-III to apoE ratios. In contrast, the
      TRL apoC-III to apoE ratio of type IV patients was similar and the ISL apoC-III
      to apoE ratio was significantly higher, compared to normolipidemic individuals.
      These results indicate that compared to normolipidemic individuals, remnant-like
      lipoproteins in the ISL fraction of type IV patients are enriched in apoC-III
      relative to apoE, whereas those of type III patients are enriched in apoE
      relative to apoC-III.

PMID- 9254068
TI  - Novel elements located at -504 to -399 bp of the promoter region regulated the
      expression of the human macrophage scavenger receptor gene in murine macrophages.
AB  - The expressions of type I and type II macrophage scavenger receptors (MSRs) are
      highly specific in macrophages and related cell types. Although some reports have
      described the regulation of MSR gene expression and proposed some cis-elements
      related to cell-specific expression, the regulation of MSR remains largely
      unclear. This is due, in part, to an unacceptably low efficiency of transfection
      into monocyte/ macrophage cells. In the present study, we optimized the
      conditions of electroporation in murine macrophage (P388D1) cells. The efficiency
      of electroporation was increased 20-fold compared with previous methods. Using
      the optimized method, we focused on studying the regulation of the human MSR
      promoter in macrophages. We presently demonstrate that: a) the proximal -10 to
      +50 bp human MSR promoter region is necessary for the cell type-specific
      expression of human MSR; b) the 6.5 kbp upstream sequence suppresses the
      expression of human MSR; c) a promoter region extending from -504 to -399 bp
      produced the greatest increase in transcriptional activity; d) macrophage cell
      specific transcription factors bind to the region as determined by
      electrophoretic mobility shift assay (EMSA) and a footprint assay; and e)
      mutations of the region reduced about 40-75% of the promoter activity in a
      transfecting assay. We concluded that novel elements located at the -504 to -399
      bp region may play an important role in the regulation of the MSR gene expression
      in macrophages. We speculate that macrophage-specific factors binding to those
      elements may be responsible for the transcription regulation of the MSR gene in
      macrophages.

PMID- 9254069
TI  - Cholesterol 7alpha-hydroxylase influences the expression of hepatic apoA-I in two
      inbred mouse strains displaying different susceptibilities to atherosclerosis and
      in hepatoma cells.
AB  - C57BL/6 mice are susceptible to diet-induced atherosclerosis, whereas BALB/c mice
      are resistant. The susceptibility of C57BL/6 mice has been linked to decreased
      plasma HDL cholesterol in response to a diet containing fat, cholesterol, and
      cholic acid. Feeding C57BL/6 mice a diet consisting of fat and cholesterol, but
      no cholic acid, increased plasma high density lipoprotein (HDL) cholesterol. The
      increase in HDL was associated with increases in both plasma apolipoprotein
      (apo)A-I and hepatic apoA-I mRNA. Supplementation of the cholesterol-rich diet
      with cholic acid inhibited the stimulatory effect of cholesterol on hepatic apoA
      I mRNA expression, resulting in similar hepatic apoA-I mRNA levels compared to
      chow-fed mice. Atherosclerosis-resistant BALB/c mice were also resistant to diet
      induced changes in plasma HDL, apoA-I, and hepatic apoA-I mRNA levels. Previous
      studies showed that the diets changed both the activity and mRNA encoding the
      liver specific enzyme 7alpha-hydroxylase (1993.J. Lipid Res. 34: 923-931). In
      both strains of mice, hepatic expression of apoA-I and 7alpha-hydroxylase mRNA
      varied in parallel. Whereas susceptible C57BL/6 mice also showed a significant
      correlation between HDL cholesterol and expression of 7alpha-hydroxylase, no such
      correlation was observed in BALB/c mice, suggesting that genetic differences in
      HDL metabolism, not hepatic apoA-I synthesis, are responsible for the strain
      specific differences in plasma HDL levels. The finding that lecithin: cholesterol
      acyltransferase (LCAT) activity was significantly decreased in C57BL/6 mice, but
      not in BALB/ c mice fed the atherogenic diet, further supports this conclusion.
      Additional studies show that McArdle hepatoma cells stably expressing plasmid
      derived rat 7alpha-hydroxylase recapitulated the parallel linear relationship
      between 7alpha-hydroxylase and apoA-I mRNA expression observed in both strains of
      mice. These data link hepatic apoA-I mRNA expression to hepatic cholesterol/bile
      acid metabolism.

PMID- 9254071
TI  - Determinants of postprandial lipemia in men with coronary artery disease and low
      levels of HDL cholesterol.
AB  - We studied the determinants of postprandial lipemia in 49 post-coronary-bypass
      men with low HDL cholesterol (< or = 1.1 mmol/l at screening). The subjects were
      given a mixed meal containing 63 g fat and 150,000 IU vitamin A. Serum was
      obtained before and 3, 4, 5, 6, and 8 h after the meal. S(f) > 400 and S(f) 12
      400 lipoproteins, LDL, and HDL were separated by ultracentrifugation; and
      triglyceride (TG), retinyl ester (RE), and apolipoprotein (apo)E concentrations
      were measured. The associations of 15 potential predictor variables with measures
      of postprandial lipemia were evaluated in univariate and multivariate models.
      Fasting TG concentration was the most important determinant of postprandial lipid
      and apoE concentrations. In univariate analyses, neither apoE phenotype nor
      common genetic polymorphisms in the apoB gene (XbaI and apoB signal peptide
      length polymorphisms), lipoprotein lipase gene (Hind III polymorphism), or apoC
      III gene (C[1100] to T sequence change) significantly predicted the magnitude of
      postprandial lipemia. In multivariate linear regression analyses, fasting TG
      concentration (P< 0.001) and postheparin plasma hepatic lipase activity (P =
      0.023) were directly, and body mass index (P = 0.007) and the presence of apoE2
      (P = 0.029) allele inversely related to the TG increment in S(f) >400
      lipoproteins. Fasting TG was associated with a high (P < 0.001) and presence of
      the SP24 allele of the apoB signal peptide gene with a low (P = 0.014) S(f) 12
      400 TG response. Fasting TG concentrations alone predicted 35%, 10%, and 34% of
      the variability in postprandial S(f) >400 responses of TG, RE, and apoE;
      multivariate models improved this predictive power to 40-50%. Even multivariate
      models were poor predictors of postprandial responses in S(f) 12-400 lipoproteins
      (0-26%). Much of the interindividual variation in the magnitude of postprandial
      lipemia remained unexplained in the present study.

PMID- 9254070
TI  - Acetyl-L-carnitine flux to lipids in cells estimated using isotopomer spectral
      analysis.
AB  - Acetyl-L-carnitine is known as a reservoir of activated acetyl units and as a
      modulator of metabolic function. The objective of this study was to quantify the
      fate of the acetyl moiety of acetyl-L-carnitine in lipogenic pathways.
      Lipogenesis was studied in an adipocyte model, differentiated 3T3-L1 cells, and a
      hepatoma cell, HepG2 cells. Lipogenesis and ketogenesis were examined in rat
      hepatocytes. Both de novo synthesis and elongation of fatty acids were
      investigated using gas chromatography/mass spectrometry and [1,2-(13)C]acetyl-L
      carnitine. Comparisons were performed with [13C]glucose and [13C]acetate.
      Isotopomer Spectral Analysis, a stable isotope method for differentiating between
      the enrichment of the precursor and the amount of synthesis was used to analyze
      the data. Acetyl-L-carnitine was generally less effective than acetate as a
      precursor for de novo lipogenesis. The effects of acetyl-L-carnitine were not
      identical to those of acetate plus carnitine as expected if acetyl-L-carnitine
      flux to acetyl CoA is controlled by carnitine acetyl transferase. Acetyl-L
      carnitine (2 mM) contributed approximately 10% of the lipogenic acetyl-CoA used
      for synthesis and elongation as well as 6% of the ketogenic acetyl-CoA. No
      differences were found between the precursor enrichment for de novo lipogenesis
      and for elongation of saturated fatty acids. Flux of acetyl-L-carnitine to lipid
      was increased, not decreased, by the ATP citrate lyase inhibitor, 
      hydroxycitrate. In contrast, flux of glucose to lipid was dramatically decreased
      by this inhibitor. These results indicate that flux of acetyl-L-carnitine to
      lipid can bypass citrate and utilize cytosolic acetyl-CoA synthesis.

PMID- 9254072
TI  - Molecular cloning and functional expression of cDNA encoding the pig plasma
      phospholipid transfer protein.
AB  - Humans and the pig show marked similarities in lipoprotein metabolism; therefore,
      the pig has been used as a model in numerous nutritional studies. Pig plasma
      displays no activity of cholesteryl ester transfer protein (CETP), which is known
      to be responsible for half of the phospholipid mass transfer in human plasma, the
      other half being accounted for by the plasma phospholipid transfer protein
      (PLTP). This makes the pig an ideal subject for the study of PLTP structure and
      function. Here we report the molecular cloning of pig PLTP and the eukaryotic
      cell expression of its complementary DNA. Pig PLTP was found to share 93% amino
      acid sequence identity with human PLTP and 81% with mouse PLTP. Tissue expression
      of PLTP mRNA was examined by a method based on reverse transcription-polymerase
      chain reaction (RT-PCR) and solid-phase minisequencing in nine pig tissues. The
      highest PLTP mRNA levels were found in the pancreas, brain, lung, and liver.
      Medium from COS-1 cells expressing PLTP possessed phospholipid transfer activity,
      and the secreted recombinant PLTP was detectable by Western blotting in the
      culture supernatant. A mutant protein with a substitution of Cys at position 22
      by Arg was found to display impaired secretion into growth medium indicating a
      role for cysteines in the correct folding of PLTP. This study forms the basis for
      future work on the structure-function relationships in pig PLTP.

PMID- 9254073
TI  - Quantification in the subnanomolar range of phospholipids and neutral lipids by
      monodimensional thin-layer chromatography and image analysis.
AB  - A sensitive, rapid, and simple method is presented for the simultaneous
      quantitation of the major phospholipids and neutral lipids using an image
      analyzer after separation by one-dimensional thin-layer chromatography. A clear
      cut separation of the lipids was achieved on one EDTA-impregnated chromatoplate
      with five step-wise developments. An image was acquired, and the integrated
      optical densities of the individual spots were quantitated by a camera-equipped
      image analyzer against an internal standard of cholesteryl formate. Calibration
      curves for each lipid followed linear or hyperbolic functions permitting
      quantification of as little as 0.015 nmol of lysophosphatidylcholine and as much
      as 7.50 nmol of triglyceride from a single application. Quantitation of the major
      lipids in human plasma by TLC and image analysis and standardized enzymatic
      methods were well correlated. The method is suitable for routine analysis of
      biological samples having lipid profiles as different as rat hepatocyte
      subcellular fractions, and very low density lipoproteins secreted by rat
      hepatocyte suspensions.

PMID- 9254074
TI  - Alternative forms of the scavenger receptor BI (SR-BI).
AB  - The class B, type I scavenger receptor has been implicated as a receptor for high
      density lipoprotein (HDL). We have isolated a murine cDNA clone encoding an
      alternative form of SR-BI that differs in the putative cytoplasmic domain of the
      receptor. This variant form, likely the result of alternative mRNA splicing, is
      designated SR-BI.2. SR-BI.2 mRNA was detected in mouse tissues known to express
      SR-BI and tissue-specific differences in the relative abundance of SR-BI.2 were
      apparent. In mouse adrenal glands, SR-BI.2 represented approximately one-third of
      total SR-BI mRNA, whereas in mouse testes, SR-BI.2 represented the major mRNA
      species (79% of total). SR-BI.2 was also detected in the human cell lines
      examined, namely HeLa, HepG2, and THP-1 cells. CHO cells transfected with the
      mouse SR-BI.2 cDNA expressed significant levels of SR-BI.2 protein and acquired
      the ability to take up fluorescent lipid (DiI) from DiI-HDL. Alternative splicing
      of SR-BI represents a potentially important process for the regulation of SR-BI
      expression and function.

PMID- 9254076
TI  - Giant fusiform intracranial aneurysms: review of 120 patients treated surgically
      from 1965 to 1992.
AB  - The paucity of information about giant fusiform intracranial aneurysms prompted
      this review of 120 surgically treated patients. Twenty-five aneurysms were
      located in the anterior and 95 in the posterior circulation. Six patients
      suffered from atherosclerosis and only three others had a known arteriopathy. The
      remaining 111 patients presented with aneurysms resulting from an unknown
      arterial disorder; these patients were much younger than those harboring
      atherosclerotic aneurysms. Mass effect occurred in only 50% of cases and
      hemorrhage in 20%. Eight aneurysms caused transient ischemic attacks. Hunterian
      proximal occlusion or trapping were dominant among the treatment methods. In
      contrast to the management of giant saccular aneurysms, the usual thrombotic
      occlusion of a giant fusiform aneurysm after proximal parent artery occlusion
      requires the presence of two collateral circulations to prevent infarction, one
      for the end vessels and another for the perforating vessels that arise from the
      aneurysm. Although there was some reliance on the circle of Willis and on
      collateral vessels manufactured at surgery, the extent of natural leptomeningeal
      and perforating collateral, thalamic, lenticulostriate, and brainstem vessels was
      astonishing and formerly unknown to the authors. Good outcome occurred in 76% of
      patients with aneurysms in the anterior circulation; two of the six cases with
      poor results included patients who were already hemiplegic. Ninety percent of
      patients with posterior cerebral aneurysms fared well. Only 67% of patients with
      basilar or vertebral aneurysms had good outcomes, although more (17%) of these
      patients were in poor condition preoperatively because of brainstem compression.

PMID- 9254075
TI  - Prolonged inhibition of cholesterol synthesis explains the efficacy of
      atorvastatin.
AB  - HMG-CoA reductase inhibitors or statins are effective in both the primary and
      secondary prevention of coronary heart disease, the extent of benefit being
      proportional to the reduction in low density lipoprotein (LDL) cholesterol
      achieved. Atorvastatin, a newly licensed compound, reportedly lowers LDL with
      greater efficacy than other statins. The mechanism of this action was, therefore,
      explored in twenty patients with refractory familial hypercholesterolemia who
      received in a single-blind sequence simvastatin 40 mg/day, placebo and
      atorvastatin 10 mg/day each for 4 weeks. At the end of the placebo period the
      effects of single 40-mg doses of simvastatin and atorvastatin on plasma levels
      and urinary excretion of mevalonic acid, indices of HMG-CoA reductase activity,
      were compared. Administration of atorvastatin 10 mg daily for 1 month lowered LDL
      cholesterol by 32.5%, compared with placebo (P = 0.0001), which was 4.5% less
      than the decrease after simvastatin 40 mg daily (P = 0.33). The area under the
      plasma curve and urinary mevalonic acid/ creatinine ratio were both significantly
      less during the 24 h after a single dose of atorvastatin 40 mg than after a
      single dose of simvastatin 40 mg (P < 0.01). These findings suggest that the
      greater efficacy of atorvastatin compared with simvastatin is due to more
      prolonged inhibition of HMG-CoA reductase, presumably reflecting longer residence
      of atorvastatin or its active metabolites in the liver.

PMID- 9254077
TI  - Contralateral approaches to bilateral cerebral aneurysms: a microsurgical
      anatomical study.
AB  - In patients with bilateral supratentorial aneurysms, surgical clipping of all
      aneurysms via a unilateral approach would obviate the need for a second
      operation. The authors conducted a microsurgical study in human cadaver heads to
      examine the contralateral exposure for four common aneurysm sites in the anterior
      circulation: the ophthalmic artery (OA) origin, the posterior communicating
      artery (PCoA) origin, the internal carotid artery (ICA) termination, and the
      middle cerebral artery (MCA) bifurcation. Frontotemporal craniotomies were
      performed in 16 cadavers to evaluate the corridor for exposure of these sites
      from the contralateral side. Morphometric data, including lengths and diameters
      of major arterial segments and optic nerves, were documented for anatomical
      correlation. In this study, the contralateral OA origin was successfully exposed
      in 62% of specimens, the PCoA origin in 50%, the ICA bifurcation in 100%, and the
      MCA bifurcation in 62%. Exposure of the OA origin and, in some cases, the PCoA,
      required incision of the falciform ligament and mobilization of the contralateral
      optic nerve. Exposure of the MCA bifurcation was dependent on the length of the
      M1 segment, with successful exposure only when this segment was shorter than 14
      mm. Implications for the contralateral approach to aneurysms at these sites are
      discussed and the microsurgical corridors for exposure are described. For
      correlation with the anatomical study, a brief clinical review of patients with
      bilateral supratentorial aneurysms treated at The Johns Hopkins Hospital between
      1992 and 1995 is presented. Guidelines for the contralateral approach to
      aneurysms are discussed with reference to the anatomical study and the clinical
      review.

PMID- 9254078
TI  - Surgical indications in patients with an intracerebral hemorrhage due to ruptured
      middle cerebral artery aneurysm.
AB  - In this retrospective study, the authors analyzed surgical outcomes in patients
      who suffered an intracerebral hemorrhage (ICH) as a result of a ruptured middle
      cerebral artery aneurysm. They studied 47 patients who underwent early aneurysm
      surgery and hematoma evacuation within 24 hours after onset of ICH. The types of
      ICH were classified into three groups according to their appearance on
      computerized tomography scanning: 1) temporal ICH; 2) intrasylvian hematoma; and
      3) ICH with diffuse subarachnoid hemorrhage (SAH). Overall, 25 patients (53%)
      achieved a favorable outcome and 18 (38%) died. Factors that could be used to
      predict a favorable outcome included age less than 60 years, temporal ICH, World
      Federation of Neurological Surgeons Grade II or III, absence of a surgical
      complication, and a hematoma volume less than 25 ml. In the patients with
      temporal ICH, eight of nine patients achieved a good recovery and no patient
      developed a surgical complication or delayed ischemic deficit. The significant
      prognostic factor in patients with an intrasylvian hematoma was surgery within 6
      hours after onset of symptoms. In patients with temporal ICH or intrasylvian
      hematoma, the results of the initial neurological examination did not accurately
      predict outcome. On the other hand, in patients with ICH and diffuse SAH, those
      patients who developed an ICH with a volume greater than 25 ml had a poor
      prognosis. These results indicate that aggressive surgical treatment should be
      performed in patients with a temporal ICH or an intrasylvian hematoma, regardless
      of the neurological findings on admission; in patients with ICH and diffuse SAH,
      a careful review of surgical indications is required.

PMID- 9254079
TI  - Intracranial aneurysms treated with the Guglielmi detachable coil: midterm
      clinical results in a consecutive series of 100 patients.
AB  - A prospective study was designed to evaluate clinical outcome in a series of 100
      consecutively treated patients who underwent endovascular embolization of 104
      intracranial aneurysms using Guglielmi detachable coils (GDCs). Midterm clinical
      outcome (2-6 years, average 3.5 years) was obtained for 94 patients and was
      classified according to a modified Glasgow Outcome Scale. Of nine patients
      treated in the acute phase of severe subarachnoid hemorrhage (Grade IV or V),
      seven died from the initial hemorrhage, one had a poor outcome, and one had a
      fair midterm outcome, with no post-GDC embolization hemorrhages. Twenty patients
      underwent subsequent surgical or endovascular procedures that did not include the
      use of GDCs. These included aneurysm clipping in nine patients and parent vessel
      sacrifice in 11 patients. None of these 20 patients experienced post-GDC
      embolization hemorrhage. The postoperative midterm clinical outcomes of these 20
      patients did not significantly differ from the outcomes of patients who underwent
      GDC embolization as their definitive treatment. Six patients died of unrelated
      causes prior to reaching the 2-year survival point, with no post-GDC embolization
      hemorrhage. The midterm outcomes of the remaining 61 patients who underwent GDC
      embolization as their definitive treatment were classified as excellent (46
      patients [75%]), good (seven patients [11%]), fair (three patients [5%]), poor
      (one patient [2%]), or dead (four patients [7%]). All four patients died from
      giant lesions. At midterm follow up, the surviving 57 patients' neurological
      statuses were unchanged or improved in 54 cases and worsened in three cases. The
      midterm post-GDC embolization hemorrhage rate was 0% for small aneurysms, 4% (one
      case) for large aneurysms, and 33% (five cases) for giant lesions. The GDC
      procedure is a safe, effective, and reliable means of preventing aneurysm
      hemorrhage in patients with small and large intracranial aneurysms. Results,
      however, are less satisfactory in cases involving giant lesions. Further follow
      up review is necessary to establish durability in the longer term. Patients with
      Grade IV or V subarachnoid hemorrhage in this series generally had poor outcomes
      even if the GDC procedure was successful in occluding the aneurysm.

PMID- 9254080
TI  - Endovascular treatment of cerebral aneurysms following incomplete clipping.
AB  - The authors report their experience using electrolytically detachable coils for
      the treatment of residual cerebral aneurysms following incomplete surgical
      clipping. Eight patients were treated for six anterior and two posterior
      circulation aneurysm remnants. All patients were referred for endovascular
      treatment by experienced cerebrovascular neurosurgeons at the authors'
      institution. Patients underwent follow-up angiography immediately after
      endovascular treatment. In seven of the eight patients, additional follow-up
      angiographic studies were obtained at periods ranging from 7 weeks to 2 years
      posttreatment. The latest follow-up angiograms demonstrated that six of the eight
      aneurysm remnants were 100% occluded, with near-complete occlusion of the other
      two aneurysm remnants. There was no permanent neurological or non-neurological
      morbidity or mortality associated with the treatment. There was no incidence of
      aneurysm hemorrhage during or after treatment. Endovascular treatment of cerebral
      aneurysm remnants following prior surgical clipping can be accomplished with
      acceptable morbidity and mortality rates. Endovascular coil occlusion can play an
      important adjunctive role in the treatment of those aneurysms that have been
      incompletely obliterated by surgical clipping.

PMID- 9254081
TI  - Cerebral cavernous malformations: natural history and prognosis after clinical
      deterioration with or without hemorrhage.
AB  - Despite recent studies of the natural history of cavernous malformations, there
      remains significant uncertainty concerning hemorrhage rates and the importance of
      lesion location. Controversy arises over varying definitions of "hemorrhage."
      What is ultimately important to the patient is the occurrence of a neurological
      event, which may or may not be associated with radiologically documented
      hemorrhage, as well as the chance of recovery after such an event. The purpose of
      this study was to determine the rates of occurrence and sequelae of neurological
      events in 173 patients referred to our vascular malformation clinic with
      cavernous malformations. All patient data were entered into a database. The mean
      age at presentation for the 173 patients was 37.5 years. The lesion location was
      deep (brainstem, cerebellar nuclei, thalamus, or basal ganglia) in 64 patients
      (37%) and superficial in 109 (63%). Thirty-one patients (18%) had multiple
      lesions. Disease presentation was due to seizures in 62 patients (36%),
      hemorrhage in 44 (25%), focal neurological deficit without documented hemorrhage
      in 35 (20%), headache alone in 11 (6%), and incidental findings in 21 patients
      (12%). The results obtained in the 110 patients eligible for follow-up review
      were used to derive information on the rates of hemorrhage and neurological
      events. An interval event (neurological deterioration) required both symptoms and
      signs. The total mean follow-up period was 46 months, the majority (65%) of which
      was prospective. There were 18 interval events in 427 patient-years of follow-up
      review, for an overall annual event rate of 4.2%. Location was the most important
      factor for predicting interval event occurrence, with significantly higher rates
      for deeply located (10.6%/year) compared with superficially located lesions
      (0%/year) (p = 0.0001). Of patients suffering a neurological event, only 37% had
      complete resolution of their deficits. This largely prospective study indicates
      that deep cavernous malformations carry a worse prognosis than superficial
      lesions with respect to annual rates of neurological deterioration. The alarming
      rate of adverse clinical events occurring in patients with deep lesions is
      punctuated by the fact that less than one-half of them recover fully during long
      term follow-up review.

PMID- 9254082
TI  - Surgical management of deep-seated dural arteriovenous malformations.
AB  - The best treatment for deep-seated dural arteriovenous malformations (AVMs)
      remains controversial. Therapeutic options include transarterial and transvenous
      embolization, surgical excision of the dural nidus, ligation of draining veins,
      and stereotactically guided radiation treatment. The authors report on their
      experience with the application and technique of skull base surgical approaches
      for deep-seated dural AVMs. Their series includes six patients who were
      surgically treated for five tentorial dural AVMs and one inferior petrosal sinus
      dural AVM between 1991 and 1995. Three patients presented with progressive
      brainstem dysfunction, one had progressive myelopathy, and two suffered
      subarachnoid hemorrhage. Venous hypertension caused progressive neurological
      deterioration in four patients and ruptured venous aneurysms caused hemorrhage in
      two patients. Four of the five tentorial dural AVMs received bilateral arterial
      supply from the internal carotid arteries and external carotid arteries (ECAs).
      The dural AVM of the inferior petrosal sinus was fed from both vertebral arteries
      and ECAs. In this series, all dural AVMs drained into deep cerebral veins. Intra-
      and postoperative angiographic studies were used to document complete
      obliteration in each case. After surgery, three patients developed transient,
      delayed (24-72 hours) neurological worsening. One month postsurgery, all six
      patients showed improvement from their preoperative neurological function.
      Surgical resection of these deep-seated dural AVMs was accomplished by
      eliminating the arterial supply rather than ligating the draining veins to avoid
      aggravating the underlying venous hypertension. This study demonstrates an
      important role for skull base surgical approaches in the management of patients
      with deep-seated dural AVMs that have hemorrhaged, are not obliterated by
      embolization, and for which stereotactically guided radiation therapy is an
      unsuitable option.

PMID- 9254083
TI  - Hemostasis and fibrinolysis activation after subarachnoid hemorrhage.
AB  - The authors assessed hemostasis and fibrinolysis serially: on admission and on
      the 1st and 7th days after surgery for subarachnoid hemorrhage (SAH), examining
      the complications of aneurysm rupture and its surgical repair. Of 32 patients, 25
      with SAH were compared with seven control patients who underwent surgery for an
      unruptured intracranial aneurysm. On admission, patients with SAH had higher
      thrombin-antithrombin III complex (TAT) levels (13.3 +/- 3.8 vs. 3.8 +/- 0.6
      ng/ml, p = 0.01), fibrin degradation product, D-dimer levels (1310 +/- 220 vs.
      556 +/- 89 ng/ml, p = 0.0001), and leukocyte counts (14.6 +/- 0.7 vs. 10.6 +/-
      1.8 x 10(9) cells/L, p < 0.05) than did control patients. Postoperative D-dimer
      values (p = 0.007) remained higher in the SAH group. Furthermore, admission D
      dimer levels were higher in the patients in poor clinical condition than in those
      in good condition (2017 +/- 377 vs. 934 +/- 208 ng/ml, p = 0.007), and D-dimer
      levels were associated with the outcome at 3 months after admission.
      Additionally, thrombin generation and fibrinolytic markers measured on admission
      were related to clinical grade, amount of subarachnoid blood seen on computerized
      tomography (CT) scanning, and patient fatality. Patients with hypodense lesions
      verified on follow-up CT scanning or with persistent neurological deficits at 3
      months had higher prothrombin fragments 1 and 2, TAT, D-dimer, and plasminogen
      activator inhibitor-1 values on the 1st day postoperatively than did patients
      without such lesions. In short, in patients with SAH, activation of coagulation
      and fibrinolysis was strongly associated with clinical state, patient fatality,
      and outcome at 3 months, and postoperatively this activation correlated with the
      development of brain infarction.

PMID- 9254084
TI  - Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor
      alpha following subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to
      ischemic brain damage. Experimental ischemia has been shown to be connected with
      the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor
      necrosis factor-alpha (TNF alpha). Increased levels of these cytokines, however,
      have not been detected thus far in patients following an SAH event. For this
      reason daily cerebrospinal fluid (CSF) samples were collected from 22
      consecutively enrolled patients with SAH and from 10 non-SAH patients (controls).
      The CSF samples were studied using immunoassays for IL-1Ra and TNF alpha to
      investigate whether an SAH caused increased cytokine levels. The mean IL-1Ra
      levels were significantly higher in patients with SAH who were in poor clinical
      condition on admission than in those who were in good condition (318 pg/ml vs. 82
      pg/ml, p < 0.02). The IL-1Ra levels increased during delayed ischemic episodes
      and after surgery in patients who were in poor clinical condition. Significant
      increases in IL-1Ra and TNF alpha were detected during Days 4 through 10 in
      patients suffering from SAH who eventually had a poor outcome (p < 0.05).
      Patients with good outcomes and control patients had low levels of these
      cytokines. The levels of IL-1Ra increased after surgery in patients with Hunt and
      Hess Grades III through V, but not in those with Grade I or II. This finding
      indicates that patients in poor clinical condition have a labile biochemical
      state in the brain that is reflected in increased cytokine levels following the
      surgical trauma. Both IL-1Ra and TNF alpha are known to induce fever, malaise,
      leukocytosis, and nitric oxide synthesis and to mediate ischemic and traumatic
      brain injuries. The present study shows that levels of these cytokines increase
      after SAH occurs and that high cytokine levels correlate with brain damage. It is
      therefore likely that fever, leukocytosis, and nitric oxide synthesis are also
      mediated by IL-1 in patients suffering from SAH and it is probable that the
      inflammatory mediators contribute to brain damage.

PMID- 9254085
TI  - Hemodynamically significant cerebral vasospasm and outcome after head injury: a
      prospective study.
AB  - The authors prospectively investigated cerebral hemodynamic changes in 152
      patients with head injuries to clarify the relationship between cerebral
      vasospasm and outcome. They also sought to determine the most clinically
      meaningful criteria for diagnosing cerebral vasospasm. Patients with varying
      degrees of moderate-to-severe head injury were monitored using transcranial
      Doppler (TCD) ultrasonography and intravenous 133Xe-cerebral blood flow (CBF)
      measurements. Outcome was determined at 6 months. Using TCD ultrasonography, mean
      flow velocities were determined for the middle cerebral artery (V(MCA), 149
      patients) and basilar artery (V(BA), 126 patients). Recordings of the mean
      extracranial internal carotid artery velocity (V(EC-ICA)) were also performed to
      determine the hemispheric ratio (V(MCA)/V(EC-ICA), 147 patients). Cerebral blood
      flow measurements were obtained in 91 patients. Concurrent TCD and CBF data from
      85 patients were used to calculate a "spasm index" (the V(MCA) or V(BA),
      respectively, divided by the hemispheric or global CBF). The authors investigated
      the clinical significance of elevated flow velocity, hemispheric ratio, and spasm
      index. Patients diagnosed as having MCA or BA vasospasm on the basis of TCD
      derived criteria alone had a significantly worse outcome than patients without
      vasospasm. When CBF was considered, hemodynamically significant vasospasm, as
      defined by an elevated spasm index, was even more strongly associated with poor
      outcome. Stepwise logistic regression analysis confirmed that hemodynamically
      significant vasospasm was a significant predictor of poor outcome, independent of
      the effects of admission Glasgow Coma Scale score and age. On the basis of the
      results of this study, the authors suggest that the important factor impacting on
      outcome is not vasospasm per se, but hemodynamically significant vasospasm with
      low CBF. These findings show that vasospasm is a pathophysiologically important
      posttraumatic secondary insult, which is best diagnosed by the combined use of
      TCD and CBF measurements.

PMID- 9254086
TI  - High-risk mild head injury.
AB  - The generally accepted definition of mild head injury includes Glasgow Coma Scale
      (GCS) scores of 13 to 15. However, many studies have shown that there is a
      heterogeneous pathophysiology among patients with GCS scores in this range. The
      current definition of mild head injury is misleading because patients classified
      in this category can have severe sequelae. Therefore, a prospective study of 1360
      head-injured patients with GCS scores ranging from 13 to 15 who were admitted to
      the neurosurgery service during 1994 and 1995 was undertaken to modify the
      current definition of mild head injury. Data regarding patients' age, sex, GCS
      score, radiographic findings, neurosurgical intervention, and 6-month outcome
      were collected and analyzed. The results of this study showed that patients with
      lower GCS scores tended to have suffered more serious injury. There was a
      statistically significant trend across GCS scores for percentage of patients with
      positive acute radiographic findings, percentage receiving neurosurgical
      interventions, and percentage with poor outcome. The presence of postinjury
      vomiting did not correlate with findings of acute radiographic abnormalities.
      Based on the results of this study, the authors divided all head-injured patients
      with GCS scores ranging from 13 to 15 into mild head injury and high-risk mild
      head injury groups. Mild head injury is defined as a GCS score of 15 without
      acute radiographic abnormalities, whereas high-risk mild head injury is defined
      as GCS scores of 13 or 14, or a GCS score of 15 with acute radiographic
      abnormalities. This more precise definition of mild head injury is simple to use
      and may help avoid the confusion caused by the current classification.

PMID- 9254087
TI  - Combined medical and surgical treatment after acute spinal cord injury: results
      of a prospective pilot study to assess the merits of aggressive medical
      resuscitation and blood pressure management.
AB  - The optimal management of acute spinal cord injuries remains to be defined. The
      authors prospectively applied resuscitation principles of volume expansion and
      blood pressure maintenance to 77 patients who presented with acute neurological
      deficits as a result of spinal cord injuries occurring from C-1 through T-12 in
      an effort to maintain spinal cord blood flow and prevent secondary injury.
      According to the Intensive Care Unit protocol, all patients were managed by using
      Swan-Ganz and arterial blood pressure catheters and were treated with
      immobilization and fracture reduction as indicated. Intravenous fluids, colloid,
      and vasopressors were administered as necessary to maintain mean arterial blood
      pressure above 85 mm Hg. Surgery was performed for decompression and
      stabilization, and fusion in selected cases. Sixty-four patients have been
      followed at least 12 months postinjury by means of detailed neurological
      assessments and functional ability evaluations. Sixty percent of patients with
      complete cervical spinal cord injuries improved at least one Frankel or American
      Spinal Injury Association (ASIA) grade at the last follow-up review. Thirty
      percent regained the ability to walk and 20% had return of bladder function 1
      year postinjury. Thirty-three percent of the patients with complete thoracic
      spinal cord injuries improved at least one Frankel or ASIA grade. Approximately
      10% of the patients regained the ability to walk and had return of bladder
      function. As of the 12-month follow-up review, 92% of patients demonstrated
      clinical improvement after sustaining incomplete cervical spinal cord injuries
      compared to their initial neurological status. Ninety-two percent regained the
      ability to walk and 88% regained bladder function. Eighty-eight percent of
      patients with incomplete thoracic spinal cord injuries demonstrated significant
      improvements in neurological function 1 year postinjury. Eighty-eight percent
      were able to walk and 63% had return of bladder function. The authors conclude
      that the enhanced neurological outcome that was observed in patients after spinal
      cord injury in this study was in addition to, and/or distinct from, any potential
      benefit provided by surgery. Early and aggressive medical management (volume
      resuscitation and blood pressure augmentation) of patients with acute spinal cord
      injuries optimizes the potential for neurological recovery after sustaining
      trauma.

PMID- 9254088
TI  - Duration of protective activity of cerebrospinal fluid shunt catheters
      impregnated with antimicrobial agents to prevent bacterial catheter-related
      infection.
AB  - This study determined the protective effect of antibacterial processing of
      cerebrospinal fluid (CSF) shunt catheters against infection with staphylococci,
      which is an important complication following CSF shunt placement for
      hydrocephalus. Also examined is the effect of a conditioning film such as that
      seen on the luminal surface of shunts used in posthemorrhagic hydrocephalus.
      Conventional preventative measures, including antimicrobial prophylaxis, confer a
      temporary or unproven benefit. The authors have therefore developed a process for
      impregnation of CSF shunts with rifampicin and clindamycin, and this has been
      shown previously to achieve the target duration of 28 days of protective activity
      in vitro. The present study demonstrates the limit of the period of protection
      and the efficacy of the processing against a wide range of staphylococci,
      particularly in the presence of a plasma protein conditioning film. Five strains
      of Staphylococcus aureus and 17 coagulase-negative staphylococci, all clinical
      isolates, were inoculated into the shunts at 2-week intervals until failure of
      antimicrobial protection occurred. The results showed that the process protected
      against all strains for between 42 and 56 days and that the conditioning film did
      not diminish the protection. Catheters processed by this method show promise of
      significant reductions in the incidence of CSF shunt infections.

PMID- 9254089
TI  - Absence of bleeding complications in patients undergoing cortical surgery while
      receiving valproate treatment.
AB  - Valproate (VPA) is associated with a variety of idiosyncratic hematological
      effects including thrombocytopenia, inhibition of platelet aggregation, and
      fibrinogen depletion. This has led some investigators to recommend
      discontinuation of VPA therapy prior to elective surgical procedures. However,
      administration of VPA therapy is not altered prior to surgery at the authors'
      center and no VPA-associated bleeding complications have been observed.
      Therefore, a retrospective chart review was conducted to verify the clinical
      observations in patients who had undergone cortical resection while receiving
      antiepileptic drugs (AEDs). Baseline, surgical, and postoperative laboratory data
      were available for a total of 313 patients, 111 of whom were receiving VPA and
      202 of whom were receiving AEDs without VPA (control patients). Eighty-seven
      percent of the patients receiving VPA were also being treated with at least one
      other AED. The control group was approximately equally divided between
      monotherapy (55%) and polytherapy (45%) treatments. Platelet counts were
      significantly lower in the control polytherapy (284 +/- 74 x 10(9)/L) and both
      VPA groups (279 +/- 113 x 10(9)/L) as compared with the control monotherapy group
      (314 +/- 85 x 10(9)/L). Baseline fibrinogen levels were significantly lower in
      the VPA than in the control groups (223 +/- 91 g/dl vs. 278 +/- 95 g/dl). Both
      pre- and postoperatively, the VPA group had lower red blood cells counts,
      hematocrit, and hemoglobin levels. There was no significant difference between
      groups in estimated blood loss during surgery or qualitative wound discharge
      postsurgery. There was only one case of a bleeding complication, which occurred
      14 days postoperatively in a patient receiving carbamazepine monotherapy. The
      results of this study confirm the clinical observations of an absence of bleeding
      complications in patients receiving VPA therapy at the time of surgery, despite
      differences in laboratory parameters.

PMID- 9254090
TI  - Cerebellar astrocytoma: experience with 54 cases surgically treated at the Mayo
      Clinic, Rochester, Minnesota, from 1978 to 1990.
AB  - A comprehensive review of the literature has shown that the treatment of choice
      for cerebellar astrocytomas has primarily been gross-total resection of the mass
      and gross-total resection of the enhancing portion of pilocytic astrocytomas.
      Most large scale studies of postresection survival rates of patients with
      cerebellar astrocytomas were conducted when computerized tomography (CT) and
      magnetic resonance (MR) imaging were not readily available. It has been shown
      that postoperative CT scans or MR images are more reliable than the surgeon's
      estimate of the degree of tumor resection at the time of surgery. It is not
      possible, therefore, to make an accurate determination regarding a postresection
      prognosis based on the degree of suspected tumor resection without the
      availability of appropriate radiographic imaging. In this study, the authors
      retrospectively evaluated the treatment of 54 patients with cerebellar
      astrocytoma who underwent surgery at the Mayo Clinic in Rochester, Minnesota,
      from 1978 through 1990. Preoperative and postoperative CT scans or MR images were
      available in all 54 patients.

PMID- 9254091
TI  - Management of primary intracranial germinomas: diagnostic surgery or radical
      resection?
AB  - Because intracranial germinomas are readily curable with radiation and
      chemotherapy or radiation therapy alone, the role of radical surgery has become
      debatable. This study assesses the optimum degree of surgical resection for
      intracranial germinomas. Twenty-nine patients who underwent surgery for germinoma
      were retrospectively analyzed (male/female ratio 27:2, median age 18 years).
      Among these 29 patients there were 10 solitary pineal, seven solitary
      neurohypophyseal/hypothalamic, and 12 multifocal or disseminated tumors. Biopsy
      samples were obtained in 16 patients (stereotactically in eight,
      transsphenoidally in four, and via frontotemporal craniotomy in four). Partial
      resection was attained in five patients (via a frontotemporal approach in three
      and occipitotranstentorially in two). Gross-total resection was achieved via an
      occipitotranstentorial route in eight patients with pineal masses. After surgery,
      10 patients were treated with radiotherapy alone, and 19 received radiation and
      chemotherapy; complete remission was achieved in all 29 patients. The overall
      tumor-free survival rate was 100% at a median follow-up period of 42 months.
      There was no significant difference in outcome related to the extent of surgical
      resection. Postoperative neurological improvement was seen in only two patients,
      whereas transient postoperative complications, mainly upgaze palsy, were observed
      in six. One patient experienced a slight hemiparesis, bringing the surgical
      morbidity rate to 3% (one of 29). It is concluded that radical resection of
      intracranial germinomas offers no benefit over biopsy. The primary goal of
      surgery should be to obtain a sufficient volume of tumor tissue for histological
      examination. If there is strong evidence of germinoma on radiological studies,
      biopsy samples should be obtained. When a perioperative histological diagnosis of
      pure germinoma is made during craniotomy, no risk should be taken in continuing
      the resection.

PMID- 9254092
TI  - Redefined role of angiogenesis in the pathogenesis of dural arteriovenous
      malformations.
AB  - To investigate the role of angiogenesis in the pathogenesis of dural
      arteriovenous malformations (AVMs), 40 rats underwent common carotid artery
      external jugular vein (CCA-EJV) anastomosis, bipolar coagulation of the vein
      draining the transverse sinus, and sagittal sinus thrombosis to induce venous
      hypertension. Fifteen rats underwent a similar surgical procedure, but venous
      hypertension was not induced. The 55 rats were divided into seven groups. Four
      groups, each containing 10 rats, underwent induced venous hypertension. The other
      three groups, each containing five rats, did not undergo induced venous
      hypertension. After 1, 2, or 3 weeks, dura mater was obtained from one group of
      hypertensive rats and from one group of nonhypertensive rats and was assayed for
      angiogenic activity (rabbit cornea bioassay). The remaining group of 10
      hypertensive rats was not assayed to determine if sampling affected dural AVM
      formation. Unlike rats without CCA-EJV anastomosis, rats with CCA-EJV anastomosis
      had significantly increased postoperative sagittal sinus pressures (p < 0.0001).
      Mean angiogenesis indices were significantly greater in rats with venous
      hypertension than in rats without venous hypertension (p = 0.004). Dural AVMs
      formed in 42% of the 55 rats and facial AVMs formed in 51%. Angiogenic activity
      correlated positively with venous hypertension (p = 0.74). Development of dural
      AVMs correlated positively with both venous hypertension (p = 0.0009) and
      angiogenic activity (p = 0.04). These data indicate that venous hypertension may
      induce angiogenic activity either directly or indirectly by decreasing cerebral
      perfusion and increasing ischemia, and that dural AVM formation may be the result
      of aberrant angiogenesis.

PMID- 9254093
TI  - Natriuretic peptide system and endothelin in aneurysmal subarachnoid hemorrhage.
AB  - The natriuretic peptide system consists of atrial natriuretic peptide (ANP),
      brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The system
      is implicated in the control of body fluid homeostasis, causes natriuresis and
      diuresis (ANP and BNP), and regulates vascular tone (CNP). A reciprocal
      relationship between ANP and endothelin (ET) has been suggested, and earlier
      studies have documented a possible role of ET in cerebral vasospasm after
      aneurysmal subarachnoid hemorrhage (SAH). The authors studied plasma ANP, BNP,
      CNP, and ET for 6 consecutive days in 13 patients with SAH by using
      radioimmunoassay. The median admission values for ANP were 31.5 pg/ml (range 16.8
      323 pg/ml [normal 15 +/- 7 pg/ml]); for BNP, 45.3 pg/ml (range 2.2-80.2 pg/ml
      [normal 12 +/- 9 pg/ml]); for CNP, 7.7 pg/ml (range < 2-20 pg/ml [normal 5.2 +/-
      3 pg/ml]); and for ET, 11 pg/ml (range 6.5-25.1 pg/ml [normal 7.2 +/- 4 pg/ml]).
      Additional increases (defined as > 100% increase on two consecutive measurements)
      were noted in ANP (11 patients), BNP (10 patients), and CNP (three patients), and
      resulted in a negative fluid balance in 10 of the 13 patients. The CNP increased
      in three of four patients with cerebral vasospasm and in one of nine patients
      without cerebral vasospasm (Fisher's exact test, p = 0.2). No major fluctuations
      in plasma ET were noted. In seven patients, the plasma ET level did not increase
      beyond 10 pg/ml during the days of measurement. In six patients, only an
      occasional sample showed an increase to a maximum of 25 pg/ml. Changes in BNP,
      ANP, and CNP were independent of each other. The authors conclude that both
      plasma ANP and BNP increase after SAH and often result in a negative fluid
      balance. Plasma ANP and BNP seem differentially regulated in the presence of SAH
      but not by the level of the plasma ET. The possible role of CNP as a regulatory
      response to cerebral vasospasm needs further exploration.

PMID- 9254094
TI  - Prevention and reversal of cerebral vasospasm by an endothelin-converting enzyme
      inhibitor, CGS 26303, in an experimental model of subarachnoid hemorrhage.
AB  - Delayed cerebral ischemia due to cerebral vasospasm is a major cause of morbidity
      and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH).
      Increasing evidence implicates the potent vasoconstrictor peptide endothelin (ET)
      in the pathophysiology of cerebral vasospasm. In the present study the authors
      examined the therapeutic value of blocking the production of ET-1 by inhibiting
      the conversion of its relatively inactive precursor, Big ET-1, to a
      physiologically active form. An inhibitor of ET-converting enzyme (ECE), CGS
      26303, was injected intravenously after inducing SAH in New Zealand white
      rabbits. Injections of CGS 26303 were initiated either 1 hour after SAH
      (prevention protocol) or 24 hours after SAH (reversal protocol). One of three
      concentrations (3, 10, or 30 mg/kg) of CGS 26303 was injected twice daily, and
      all animals were killed by perfusion fixation 48 hours after SAH occurred.
      Basilar arteries were removed and sectioned, and their cross-sectional areas were
      measured in a blind manner by using computer-assisted videomicroscopy. Treatment
      with CGS 26303 attenuated arterial narrowing after SAH in both the prevention and
      reversal protocols. The protective effect of CGS 26303 achieved statistical
      significance at all dosages in the prevention protocol and at 30 mg/kg in the
      reversal protocol. These findings demonstrate that inhibiting the conversion of
      Big ET-1 to ET-1 via intravenous administration of an ECE inhibitor can be an
      effective strategy for limiting angiographic vasospasm after SAH. Moreover, the
      results demonstrate that treatment with the ECE inhibitor is capable of reducing
      vasospasm even when initiated after the process of arterial narrowing has begun.
      Finally, the results provide further support for the role of ET in the
      establishment of cerebral vasospasm. The ECE inhibitor CGS 26303 thus represents
      a promising therapeutic agent for the treatment of cerebral vasospasm following
      aneurysmal SAH.

PMID- 9254095
TI  - Source and cause of endothelin-1 release into cerebrospinal fluid after
      subarachnoid hemorrhage.
AB  - Despite years of research, delayed cerebral vasospasm remains a serious
      complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed
      that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis
      in a series of experiments. In a primate model of SAH, serial ET-1 levels were
      measured in samples from the perivascular space by using a microdialysis
      technique and in cerebrospinal fluid (CSF) and plasma during the development and
      resolution of delayed vasospasm. To determine whether elevated ET-1 production
      was a direct cause of vasospasm or acted secondary to ischemia, the authors also
      measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To
      elucidate the source of ET-1, they measured its production in cultures of
      endothelial cells and astrocytes exposed to oxyhemoglobin (10 microM),
      methemoglobin (10 microM), or hypoxia (11% oxygen). There was no correlation
      between the perivascular levels of ET-1 and the development of vasospasm or its
      resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by
      vasospasm (CSF ET-1 levels were 9.3 +/- 2.2 pg/ml and ET-1 plasma levels were 1.2
      +/- 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 +/
      1.7 pg/ml in CSF and 2.7 +/- 1.5 pg/ml in plasma). Transient cerebral ischemia
      evoked an increase of ET-1 levels in CSF (1 +/- 0.4 pg/ml at the occlusion vs.
      3.1 +/- 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal
      (0.7 +/- 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture
      showed inhibition of ET-1 production 6 hours after exposure to hemoglobins.
      Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 +/- 0.8
      pg/ml vs. 0.1 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and
      at 48 hours (6.4 +/- 0.6 pg/ml vs. 0 +/- 0.1 pg/ml, control vs. hypoxic
      endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET
      1 at 6 hours (1.5 +/- 0.6 vs. 6.4 +/- 1.1 pg/ml, control vs. hypoxic astrocytes;
      p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells,
      during hypoxia and is released from the brain after transient ischemia. There is
      no relationship between ET-1 and vasospasm in vivo or between ET-1 and
      oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1
      levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the
      result of cerebral ischemia rather than reflecting the cause of cerebral
      vasospasm.

PMID- 9254096
TI  - The complement membrane attack complex and the bystander effect in cerebral
      vasospasm.
AB  - Activation of complement results in formation of membrane attack complexes (MACs)
      that can insert themselves either into cells that initiate complement activation
      or into nearby ("innocent bystander") cells. The MACs form large-conductance,
      nonspecific ion channels that can cause lytic or sublytic cell damage. The
      authors used a highly sensitive patch clamp technique to assess the contribution
      of the bystander effect to the pathophysiology of cerebral vasospasm. They
      compared the effect of complement activation by autologous aged versus fresh
      erythrocytes on the membrane conductance of freshly isolated rat cerebral artery
      smooth-muscle cells. In the presence of autologous serum aged, but not fresh,
      erythrocytes caused a large increase in membrane conductance, an effect that was
      prevented by heat-inactivating the serum. Ethyleneglycol tetraacetic acid in the
      presence of Mg++ attenuated the effect, indicating that complement activation was
      taking place via the classic pathway. The effect was reproduced by zymosan
      activated autologous serum, suggesting that such changes in conductance could
      result from insertion of MACs secondary to a bystander effect. Both C8- and C9
      depleted heterologous sera produced minimal effects that were converted to full
      effect by addition of the missing complement component. Superoxide dismutase plus
      catalase did not attenuate the conductance changes produced by autologous serum
      plus aged erythrocytes. Autologous serum plus aged erythrocyte membrane ghosts
      that were free of lysate caused a typical increase in conductance. This study
      demonstrates that complement activation by aged erythrocytes can result in MAC
      insertion into innocent bystander smooth-muscle cell membranes and that this
      mechanism, heretofore undescribed, may contribute to development of vasospasm
      after subarachnoid hemorrhage.

PMID- 9254097
TI  - Effects of serotonin on cerebral circulation after middle cerebral artery
      occlusion.
AB  - Serotonin (5-HT) produces constriction of peripheral collateral blood vessels.
      Using an animal model, the authors tested the hypothesis that 5-HT constricts
      collateral vessels in the cerebrum. A branch of the middle cerebral artery (MCA)
      was occluded proximally and cannulated distally in anesthetized dogs. Blood flow
      to the area at risk for infarction was detected by perfusing the cannulated MCA
      branch with microsphere-free blood during systemic injection of radioactive
      microspheres (shadow flow technique). Blood flow to collateral-dependent and
      normal cerebrum was measured during intravenous infusion of 5-HT (10 and 40
      mg/kg/minute). Serotonin produced a dose-related reduction of blood flow to
      collateral-dependent cerebrum, increased collateral vessel resistance in large
      cerebral arteries and collateral vessels, and decreased cerebral artery perfusion
      pressure. In contrast, blood flow to normal cerebrum was not altered because a
      decrease in small vessel resistance effectively compensated for a decrease in MCA
      perfusion pressure. These findings indicate that 5-HT produces constriction of
      collateral vessels in the cerebrum. This response is clearly different from
      normal small cerebral vessels, which dilate during 5-HT infusion.

PMID- 9254098
TI  - Microcirculation after cerebral venous occlusions as assessed by laser Doppler
      scanning.
AB  - Research on cerebral venous circulation disturbances (CVCDs) has been limited
      partly by the paucity of animal models that produce consistent venous infarction.
      Occlusion of two adjacent cortical veins in rats by means of a photochemical
      thrombotic technique provides a minimally invasive, clinically relevant, and
      reproducible model suited to study the pathophysiology of CVCDs. In this study,
      the effects of venous occlusion on regional cortical blood flow and the brain
      damage that ensues were evaluated. Cortical vein occlusion was induced by
      photoactivation of rose bengal via 100-microm fiberoptic illumination. The
      cerebral venous flow pattern was examined using fluorescence angiography until 90
      minutes after venous occlusion, and regional cerebral blood flow (rCBF) was
      determined at 48 locations by using laser Doppler scanning. Histological damage
      was assessed 48 hours after vein occlusion. Occlusion of two cortical veins
      (Group T; seven animals) was compared with single-vein occlusion and its ensuing
      brain damage (Group S; five animals) and with sham-operated control (five
      animals). An rCBF reduction occurred 30 minutes after occlusion in Group T and
      was more extensive than the decrease in Group S after 60 minutes. Observation
      frequency histograms based on local CBF data obtained in Group T demonstrated
      that local CBF at some sites decreased to a level below the ischemic threshold
      within 90 minutes. Six of the seven rats in Group T had a growing venous thrombus
      with extravasation of fluorescein. The resulting infarction was significantly
      larger in Group T (9.8 +/- 4.5% of the hemispheric area) than in Group S (only 3
      +/- 1.5% of the hemispheric area). In conclusion, microcirculation perturbations
      occur early after venous occlusion and result in the formation of a venous
      thrombus accompanied by local ischemia and severe venous infarction. The extent
      of vein occlusion determines the resulting brain damage. Based on the results of
      this study, the authors conclude that CVCDs may be attenuated by prevention of
      venous thrombus progression together with the use of protective measures against
      the consequences of ischemia.

PMID- 9254099
TI  - Expression and activation of epidermal growth factor receptors in meningiomas.
AB  - Previous studies have demonstrated expression of epidermal growth factor
      receptors (EGFRs) in human cerebral meningiomas. However, the activation status
      of the EGFRs and whether they activate cytoplasmic mitogenic signaling pathways
      are not known. In this study, using Northern blot analysis and the polymerase
      chain reaction, the authors report expression of epidermal growth factor,
      transforming growth factor-alpha, and EGFR messenger RNA in 27 meningioma
      specimens. Using Western blot and immunohistochemical analyses of the meningioma
      samples, the authors demonstrate that the EGFRs expressed by these meningiomas
      are activated. These activated EGFRs interact with and phosphorylate Shc, an SH2
      domain-containing adapter protein that is important in transducing mitogenic
      signals from EGFRs to the nucleus via activation of the Ras signaling pathway.
      These results support the concept that activation of EGFRs in human meningiomas
      by autocrine/paracrine stimulation may contribute to their proliferation.

PMID- 9254100
TI  - Penetration of the optic chiasm by a ruptured anterior communicating artery
      aneurysm. Case report.
AB  - There are few reports of anterior communicating artery aneurysms causing visual
      symptoms, and penetration of the optic chiasm by such aneurysms has not been
      reported. A 40-year-old man presented with the abrupt onset of left homonymous
      hemianopsia, right visual acuity disturbance (finger counting), and slight
      headache. Angiography disclosed a 7-mm anterior communicating artery aneurysm
      projecting inferiorly. After the neck of the aneurysm was clipped, the dome of
      the aneurysm was resected. The operation confirmed that the aneurysm had
      penetrated the right half of the optic chiasm and the thrombosed dome had also
      compressed the right optic tract. Although the aneurysm was successfully clipped,
      the visual disturbance persisted after surgery, suggesting that the damage to the
      visual pathways by aneurysm penetration was irreversible in this case.

PMID- 9254101
TI  - Tumor seeding following stereotactic biopsy of brain metastases. Report of two
      cases.
AB  - In a series of 22 patients treated with gamma knife surgery for brain metastasis
      in whom biopsy specimens were obtained via stereotactically guided procedures
      before the radiosurgical treatment was administered, two cases with evidence of
      tumor seeding were observed on subsequent follow-up examination. These findings
      contradict the opinion that the risk for tumor spread after a biopsy is
      negligible. This evidence may be explained by the fact that radiosurgery leaves
      the surrounding tissue unaffected by the treatment, which results in preserved
      anatomy around the tumor. This allows the surgeon to define the previous biopsy
      channel and, consequently, whether a distant tumor recurrence may have resulted
      from tumor seeding related to the biopsy procedure. Additionally, radiosurgical
      treatment leaves tumor cells that may have been spread as a result of the biopsy
      unaffected, giving them the potential to divide and develop into a new tumor. In
      contrast to this, microsurgical removal of the tumor will affect the surrounding
      tissue, making it impossible to detect whether new metastases are resulting from
      seeding. Furthermore, conventional fractionated radiation therapy will sterilize
      tumor cells that may have spread, thus making it impossible for these cells to
      regrow. The authors conclude that the risk for tumor seeding following a
      stereotactically guided biopsy may be higher than previously assumed.

PMID- 9254102
TI  - Giant chondroma of the falx.

PMID- 9254103
TI  - Posterior rhizotomy.

PMID- 9254104
TI  - Cerebral blood flow and vasoresponsivity.

PMID- 9254105
TI  - Informed consent.

PMID- 9254106
TI  - Cavum septum pellucidum cysts.

PMID- 9254107
TI  - Cavum septum pellucidum cysts.

PMID- 9254108
TI  - Inhibitory effects of Korean folk medicine 'Hi-Chum' on histamine release from
      mast cells in vivo and in vitro.
AB  - The effect of aqueous extract of Siegesbeckia glabrescence (Compositae) whole
      plants (SGWP) on systemic or local anaphylaxis was studied. SGWP inhibited
      compound 48/80-induced systemic anaphylaxis 100% with a dose of 1000 mg/kg. Oral
      administration of SGWP (100 mg/kg) showed a marked inhibition rate in local
      immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis reaction. When SGWP
      was pretreated at concentration ranging from 0.1 to 1000 mg/kg, the serum
      histamine levels were reduced in a dose-dependent manner. Moreover, SGWP dose
      dependently inhibited the histamine release from peritoneal mast cells by
      compound 48/80. These results indicate that SGWP possess strong antianaphylactic
      activity by inhibition of histamine release from mast cells.

PMID- 9254109
TI  - Phytochemical and biological study of radal Lomatia hirsuta (Proteaceae).
AB  - The anti-inflammatory property of Lomatia hirsuta (Lam.) Diels ex Macbr.
      (Proteaceae), leaves (radal), a plant used in Chilean traditional medicine for
      bronchial troubles and asthma, was evaluated. The biological assays showed
      infusion of L. hirsuta leaves inhibits the inflammation induced by lambda
      carrageenan corresponding to a 29.2% anti-inflammatory effect, and to 53.5% of
      the maximum effect observed with sodium naproxen (4 mg/kg) in the same
      experimental conditions. The coumarins, umbelliferone and scopoletin, were the
      major compounds isolated, along with quercetine, rhamnetin and iso-rhamnetin,
      with minor quantities or quercitrine and no presence of toxic naphthoquinone
      derivates. These results supported the folk use of L. hirsuta.

PMID- 9254110
TI  - Biological and chemical study of paico (Chenopodium chilense, Chenopodiaceae).
AB  - The methanolic extract of the aerial portion of Chenopodium chilense Schrad.,
      used in Chilean traditional medicine as a remedy for stomach-ache, has been found
      to exert the major spasmolytic activity in acetylcholine contracted rat ileum.
      This extract, with a complex flavonoid patterns on thin layer chromatography
      (TLC) analysis, is practically non-toxic both for rats and brine shrimp Artemia
      salina in acute toxicity test.

PMID- 9254111
TI  - Studies on in vivo antitussive activity of Leucas lavandulaefolia using a cough
      model induced by sulfur dioxide gas in mice.
AB  - The methanol extract of Leucas lavandulaefolia was investigated for its effects
      on a cough model induced by sulfur dioxide gas in mice. It exhibited significant
      antitussive activity when compared with control in a dose-dependent manner. The
      antitussive activity of the extract was comparable to that of codeine phosphate
      (10 mg/kg), a prototype antitussive agent. The Leucas lavandulaefolia extract at
      100, 200, and 400 mg/kg. p.o. showed inhibition of cough by 35.0, 51.9, and 56.5%
      within 1 h of performing the experiment.

PMID- 9254112
TI  - Antiemetic efficacy of ginger (Zingiber officinale) against cisplatin-induced
      emesis in dogs.
AB  - Effect of ginger (Zingiber officinale Roscoe, Zingiberaceae) extracts (acetone,
      50% ethanolic and aqueous) were investigated for antiemetic activity against
      emesis induced by 3 mg/kg cisplatin (the 100% emetic dose i.v.) in-healthy
      mongrel dogs. The acetone and 50% ethanolic extract at the doses of 25, 50, 100
      and 200 mg/kg p.o. exhibited significant protection while aqueous extract at
      these doses was ineffective against cisplatin emesis. The acetone extract was
      more effective than ethanolic extract. However, both were less effective when
      compared to 5-HT3 receptors antagonist-granisetron. Neither of the ginger extract
      was effective against apomorphine-induced emesis. The findings suggest that
      ginger could be an effective and cheap antiemetic adjunct to cancer chemotherapy.

PMID- 9254113
TI  - Quantitative ethnopharmacological study of the Campidano Valley and Urzulei
      district, Sardinia, Italy.
AB  - A new method has been developed for quantitative, phytotherapeutical analysis
      with a goal to create a general tool suitable for a wide range of research
      situations. This tool would allow one to gather data in such a format as to
      facilitate comparison with studies from other areas. The method was applied to
      data gathered from two sites in Sardinia, Italy (Campidano and Urzulei). Analysis
      was performed on 2635 responses (a) by plant, (b) by plant part, (c) by medicinal
      preparation and (d) by therapeutic use. This yielded specificity indexes which
      proved useful in comparing phytotherapeutic applications in the two geographic
      areas under study. In Urzulei the original phytotherapeutic heritage is deeply
      rooted in the local socio-economic history and clearly reflects the area's
      geographic isolation. Indeed, in this area, there is little reliance on modern
      health care. On the other hand, in Campidano, the body of phytotherapeutic
      application is more extensive. Indeed, due to migration-and to a lesser extent
      isolation- the latter area has been more affected by technological interference
      and cultural overlapping. In this area attention is widely focused on such modern
      ailments as glycemia, hypertension and constipation.

PMID- 9254114
TI  - Antinociceptive activity of Channa striatus (haruan) extracts in mice.
AB  - Haruan, Channa striatus, is a snakehead fish consumed in many parts of the
      southeast Asian region. It is believed to promote wound healing, as well as
      reduce post-operative pain. In an attempt to establish the scientific basis for
      the alleged pain-relieving benefits of this fish, we studied the antinociceptive
      effects of whole fillet and mucus extracts from haruan in the mouse using the
      abdominal constriction and tail flick tests. In the abdominal constriction test,
      the 30 min fillet extract exhibited concentration-dependent inhibition of the
      writhing response in the 10-50% concentration range, with 20% as the IC50 value.
      This activity was not dependent on the duration of extraction, with no
      significant differences among the extracts obtained at durations of 10, 20, 30,
      60, 90 and 120 min (range between 45-54% inhibition at 20% concentration). The
      mucus extract also showed concentration-dependent inhibition of the abdominal
      constriction response-at the highest concentration used the average inhibition
      was 68.9%, while IC50 value was 25%. Neither the fillet extract (30 min, 20%) nor
      the mucus extract (25%) had any demonstrable effect on the tail flick latency on
      their own, but significantly enhanced the antinociceptive activity of morphine in
      this assay. Similarly, low concentrations of the mucus and fillet extract
      enhanced the effects of morphine in the abdominal constriction test.
      Collectively, these results suggest a scientific basis for the folklore practice
      of eating haruan fish in the post-operative period for pain relief: Haruan
      extracts have antinociceptive activity and enhance the activity of other
      antinociceptive agents.

PMID- 9254115
TI  - Antimalarial activity of extracts and fractions from Bidens pilosa and other
      Bidens species (Asteraceae) correlated with the presence of acetylene and
      flavonoid compounds.
AB  - After interviewing natives and migrants from the Amazon region of Brazil about
      plants traditionally used for treatment of malaria fever and/or liver disorders,
      we selected and identified 41 different species, including the native Bidens
      (Asteraceae). We have undertaken an antimalarial study of Bidens pilosa and other
      species of Bidens from abroad. The crude ethanol extracts (whole plant, leaves
      and roots) and the chloroform and butanol fractions from B. pilosa at
      concentrations of 50 microg/ml caused up to 90% inhibition of Plasmodium
      falciparum growth in vitro. In vivo the fractions caused partial reduction of
      Plasmodium berghei parasitemia in mice. The ethanol extracts from nine different
      Bidens species collected outside Brazil were tested, and seven inhibited parasite
      growth in vitro by 65-91%. As B. pilosa appears to be a promising antimalarial
      agent, we further characterized the substances responsible for such activity.
      HPLC analysis using a photo diode-array detector showed phenyl acetylene and
      flavonoids in the ethanol extract from the leaves and roots. The chloroform
      fractions from the roots, which caused 86% inhibition of parasite growth in
      vitro, contained a major component identified as 1-phenyl-1,3-diyn-5-en-7-ol
      acetate. The association of antimalarial activity and the presence of acetylene
      compounds is discussed. In summary, all species of Bidens which had aliphatic
      acetylenes (6-14 each) were also very active, whereas extracts of B. parriflora
      and of B. bitternata with none or the three acetylenes, respectively as reported
      in literature, were inactive or had a borderline activity in vitro.

PMID- 9254116
TI  - Anti-oedematous activities of the main triterpendiol esters of marigold
      (Calendula officinalis L.).
AB  - Separation and isolation of the genuine faradiol esters (1, 2) from flower heads
      of Marigold (Calendula (officinalis L., Asteraceae) could be achieved by means of
      repeated column chromatography (CC) and HPLC for the first time. Structure
      elucidation of faradiol-3-myristic acid ester 1, faradiol-3-palmitic acid ester 2
      and psi-taraxasterol 3 has been also performed, without any previous degradation
      by means of MS, 1H-NMR, 13C-NMR and 2D-NMR experiments. The anti-oedematous
      activities of these three compounds were tested by means of inhibition of Croton
      oil-induced oedema of the mouse ear. Both faradiol esters showed nearly the same
      dose dependent anti-oedematous activity and no significant synergism appeared
      with their mixture. The free monol, psi-taraxasterol, had a slightly lower
      effect. Furthermore, faradiol was more active than its esters and than psi
      taraxasterol and showed the same effect as an equimolar dose of indomethacin.

PMID- 9254117
TI  - [Allergy to mosquitoes and use of new immunobiological parameters].
AB  - With regard to an observation of anaphylaxis after a mosquito bite, we have shown
      by new immunobiological parameters and clinical investigations: Skin tests,
      specific IgE, Tests of Activation of basophils by flow cytometry (on basophils
      and total blood) and measurement of Leucotriene LTC4, the objective reality of
      the mechanism of IgE-dependent hypersensitivity (HS). This observation is
      correlated with rare work in support of true IgE-mediated allergy to mosquito 9
      authors having used skin tests, PK in 1984 and immunoblot.

PMID- 9254118
TI  - [Acute or chronic food allergy: adapted therapeutic and diagnostic procedures].
AB  - In food allergy the allergen may present two very different clinical pictures:
      acute allergy (urticaria, bronchospasm, anaphylaxis) and chronic food allergy
      (eczema, rhinitis, digestive problems). These two syndromes are rarely separated
      in the literature on the subject although positive diagnosis is made on very
      different elements in the two cases. Furthermore, therapy, especially the diet,
      must be adapted in the two different cases of allergy.

PMID- 9254119
TI  - [Food allergens].
AB  - Perhaps more than any other kind of allergen, search for a food allergen seems to
      be difficult. There should be no bias about the usual allergens found in our
      food, that are a source of pathology that is less spectacular than shocks or
      giant urticaria that are provoked by easily recognised causes. Crossed allergies
      must be recognised in their overall features. This may give decisive aid in the
      etiological approach by facilitating understanding of the symptoms and the
      discovery of potential triggering allergens which are systematically sought.

PMID- 9254120
TI  - [Bioclinical interest in the assay of leukotrienes in four cases of sensitization
      to trophallergens].
AB  - New cellular tests as flow cytometry and leukotriene release having been set up
      for allergy diagnosis, we checked the reliability of the LTC4 release test for 4
      patients sensitized to wheat flour, oyster and lobster and to anise. Food allergy
      diagnosis was based on the clinical history, skin tests (pricks and IDR) and
      specific IgE. After allergen stimulation, LTC4 released was determined by an RIA
      method using a monoclonal antibody. The allergen extracts used for skin tests and
      LTC4 release having the same origin, LTC4 release test showed a good correlation
      with the clinical history whereas specific IgE determinations were less
      sensitive. Skin tests were negative in the cases.

PMID- 9254121
TI  - [Diagnosis of delayed type hypersensitivity to Candida albicans. Evaluation of
      lymphocyte activation by flow cytometry (171 observations)].
AB  - Abnormal delayed-type hypersensitivy to Candida albicans, since it results in an
      excessive reaction of the immune system, is very difficult to diagnose. This
      study shows that the syndromic reaction observed after intradermal injection of
      an extract of Candida albicans, in patients suspected of abnormal delayed-type
      hypersensitivy to this antigen, is associated with the presence of specific
      circulating T cells, detectable through cell culture in the presence of Candida
      albicans. There is a very significant correlation between the clinical symptoms,
      the cutaneous tests, and the lymphocyte activation tests. This abnormal
      reactivity essentially involves the CD8 cells.

PMID- 9254122
TI  - [Clinical signs of food allergy].
AB  - To investigate the clinical signs of food allergy is to open new horizons for the
      understanding of worrying acute symptoms for the patients and too often only
      symptomatic treatment. It is also possible to take control in a more logical way
      of illnesses that are classified as chronic and so incurable. The clinical
      examination requires great attention and much listening. Urticaria, eczema,
      rhinitis, asthma, colitis are the most frequent symptoms. More rarely, there may
      be certain migranes or lipoid nephrosis in children.

PMID- 9254123
TI  - [Treatment and prevention of food allergy].
AB  - Treatment of food allergy is above all etiological, and needs suppression of the
      food on condition: that it has been proven to be responsible, that it is not
      indispensible to nutrition. The etiological treatment may be associated with drug
      treatment: the anaphylactic reaction can be treated with adrenalin and
      corticosteroids, then chronic food allergy may be prevented or treated by: Sodium
      cromoglycate (Nalcron, Intercron). Ketotifen (Zaditen). Second generation anti-H1
      that has a stronger anti-allergic action (Cetrizine, Loratidine). Immunotherapy
      or really habituation to the food is possible in some casas, but progress by
      ingestion of the food may be extremely slow. Prevention includes: Food of the
      pregnant and nursing woman: the mother should have a varied diet without
      excessive consumption of any food. For atopic infants diversification of foods
      should be late. Information to parents is essential.

PMID- 9254124
TI  - [Urban atmospheric pollution and human public health].

PMID- 9254125
TI  - [Implantable cardioverter-defibrillators and mortality after myocardial infarct].

PMID- 9254126
TI  - [The implantable cardioverter-defibrillator: the Portuguese experience].
AB  - OBJECTIVE: The aim of this study was to review the Portuguese experience with
      implantable cardioverter-defibrillator therapy (ICD), in order to evaluate the
      increase in the number of ICD implanted, the main indications for this kind of
      therapy, the technical evolution of the procedure and the results of the follow
      up of these patients during the last five years. PATIENT SELECTION: The study
      group consists of 58 patients, 53 male and 5 female, mean age 54 +/- 14 years
      with ICD implanted in our country since 1992. The ICDs were implanted in 4
      Hospitals, namely, Santa Cruz Hospital with 36 patients, Santa Maria Hospital
      with 11, Santa Marta Hospital with 8 and Coimbra University Hospital with 3
      patients. Twenty six patients were resuscitated from cardiac arrest and the other
      32 had ventricular tachycardia (VT) not tolerated haemodynamically and refractory
      to therapy. The diagnosis was coronary artery disease in 31 patients, dilated
      cardiomyopathy in 8, valvular disease in 4, congenital cardiopathy in 3, right
      ventricular dysplasia in 2, congenital long QT syndrome in 1, hypertrophic
      cardiomyopathy in one. Seven patients had idiopathic ventricular fibrillation
      without structural heart disease and one patient had isolated right ventricular
      dilatation. METHODS: All patients underwent electrophysiological study before ICD
      implantation. In 2 patients epicardial leads were used and in the remaining 56
      patients a transvenous approach was used. The device was implanted in an
      abdominal position in 36 patients and in a pectoral position in 22.
      Defibrillation and pacing thresholds were measured during the implantation
      procedure and whenever necessary. Patients were followed up on an outpatient
      basis with evaluation of the number of arrhythmic episodes, therapy efficacy with
      reprogramming of the device when required. RESULTS: The number of implantations
      has increased, from 4 devices implanted in 1992, to 32 in 1996. The implantation
      was successful and without mortality or complications in all patients.
      Defibrillation threshold was 16 +/- 3 J, with an electrode impedance of 48 +/- 9
      Ohms. During a mean follow-up time of 18 +/- 15 months (1 to 56) 5 patients died,
      one of sudden death and 4 of non cardiac deaths, 15 patients were re-admitted to
      hospital and in 8 patients the device was replaced due to exhaustion. In this
      period, 37 patients (64%) had arrhythmic episodes detected by the device, 32
      patients (55%) had shocks and 9 (16%) were treated with anti-tachycardia pacing.
      Inappropriate shocks were observed in 10 patients (17%). The ICD were
      reprogrammed in 11 patients. CONCLUSIONS: Portuguese experience with IC
      implantation is increasing and has shown to be a safe procedure with no operative
      mortality or morbidity. The incidence of appropriate shocks was high with a good
      efficacy in sudden death reduction.

PMID- 9254127
TI  - [A clinical case of restrictive myocarditis due to senile-type amyloidosis].
AB  - We describe the case of a patient with restrictive cardiomyopathy due to primary
      amyloidosis associated with aging. The patient had a complex myocardial function.
      A brief review is made of the etiology, diagnostic procedures and therapy of this
      clinical entity, which is an important rare cause of cardiac death in elderly
      patients.

PMID- 9254128
TI  - [The echocardiographic diagnosis of a rare complication of an aneurysm of the
      sinus of Valsalva].
AB  - We report the case of a patient with complete heart block caused by extension of
      a congenital aneurysm of the sinus of Valsalva into the upper interventricular
      septum, which was diagnosed by transthoracic and transesophageal
      echocardiography. We emphasize the rarity of this pathology and the value of
      transesophageal echocardiography in its assessment, providing a complete
      anatomicofunctional characterization and allowing surgical repair without
      previous cardiac catheterization.

PMID- 9254129
TI  - [The importance of the endothelium in heart failure].
AB  - The endothelium is involved in cardiac and vascular dysfunction characteristic of
      heart failure. Vascular dysfunction has been related either to an impaired
      endothelium dependent vasodilation of both capacitance and resistance vessels, or
      to an increase in the plasmatic levels of endothelium derived contracting
      factors, such as endothelin-1. While the former seems to respond favourably to
      ACE-inhibitors, physical training and L-arginine; the latter will soon be
      treatable with endothelin-1 A e B receptor antagonists or with inhibitors of its
      converting enzyme. Cardiac dysfunction may be explained not only by the loss of
      the positive inotropic effect induced by low concentrations of nitric oxide
      (produced by the constitutive NO-synthase in the normal endothelium), but also by
      the negative inotropic effect induced by the high concentrations of nitric oxide,
      produced as a consequence of the stimulation of the inducible NO-synthase. It is
      therefore conceivable that cardiac dysfunction would also improve with the
      administration of drugs presently used to correct endothelium dependent
      vasodilatation disturbances.

PMID- 9254130
TI  - Attempt to solubilize Na+/K+-exchanging ATPase with amphiphilic peptide PD1.
AB  - The effect of the 24-amino-acid-long peptide, PD(1), on rat cerebral cortical
      Na+/K+ -exchanging ATPase (EC 3.6.1.37) has been studied. Incubation of the
      enzyme preparation (25 degrees C for 10-25 min) with the peptide (10(-7) - 10(-4)
      M) did not appreciably affect the activity of the enzyme, only 5-8% activation
      being registered. On the other hand, PD(1) completely eliminated the cooperative
      nature of Na+ -binding to Na+/K+ -exchanging ATPase (n(H) decreased from 1.4 to
      0.9) and slightly (1.2-fold) decreased the affinity for Na+. ATP, a substrate of
      activity for Na+/K+ -exchanging ATPase, blocked the PD(1)-promoted effect on the
      cooperativity for Na+. Incubation of cerebral cortical membranes with 5 x 10(-4)
      M PD(1) revealed a shift (from 19.5 degrees C to 21.4 degrees C) of the typical
      break on the Arrhenius plot (15-37 degrees C). Prolonged incubation of enzyme
      preparation (25 degrees C for 1-2 h) with PD(1) (4.5 x 10(-4) - 0.7 x 10(-2) M)
      followed by centrifugation of the mixture at 53,000 g for 90 min, resulted in
      loss of the activity both in the supernatant and the sediment, while the protein
      content in the supernatant and the sediment remained unchanged. After a short
      incubation (25 degrees for 10 min) with PD(1) (1 x 10(-6) M), followed by
      centrifugation, the full activity of Na+/K+ -exchanging ATPase in the sediment
      was restored. These data suggest that peptitergent PD(1) does not solubilize the
      transmembrane protein Na+/K+ -exchanging ATPase, although it abolishes the
      cooperative effect of Na+.

PMID- 9254131
TI  - Examination-induced distress in a public examination at the completion of
      secondary schooling.
AB  - BACKGROUND: The context for this study was the Higher School Certificate
      examination in New South Wales, Australia. AIMS: The main research aim was to
      investigate the association between the Higher School Certificate, the reported
      distress and anxiety levels of the adolescent students who prepare for and sit
      for the examination, and various other internal and environmental variables.
      SAMPLE: The random sample consisted of 445 students in their last two years of
      secondary schooling, with approximately equal numbers of males and females from a
      diverse range of ethnic backgrounds. METHODS: Analysis was carried out using
      principal components analysis and multiple regression. RESULTS: The most
      significant contribution to distress associated with the examination was made by
      the personality trait, anxiety proneness. Lower socio-economic status, self
      confidence, academic and verbal self-concepts and perceived ability to cope were
      also found, to a lesser extent, to be associated with increased distress. The
      interactions sex with ethnic background and year with ethnic background were of
      particular interest. Students who were male and had an English speaking
      background, and students in year 11 who had an English speaking background were
      least likely to experience distress than others in the context of the
      examination. CONCLUSIONS: Whilst results must be treated with caution, particular
      groups of students potentially vulnerable to distress were identified and
      directions for future research indicated.

PMID- 9254132
TI  - Teachers' views on bullying: definitions, attitudes and ability to cope.
AB  - BACKGROUND: Teachers play a crucial role in preventing and managing the
      widespread problem of bullying. Despite this, scant attention has been paid to
      their views on this type of problem. AIMS: To determine (i) what behaviours
      teachers regard as bullying; (ii) teachers' attitudes towards bullying, bullies
      and victims; (iii) teachers' self-beliefs about their ability to deal with
      bullying and their need for training; (iv) teachers' views of their
      responsibility for bullying in various locations; (v) the impact of length of
      service on attitudes and perceived ability to cope with bullying. SAMPLE: Pre-,
      infant, junior, and secondary school teachers (N = 138) from schools selected on
      a convenience basis. Age range 19 to 57 years (mean = 35.8), length of teaching
      experience range one to 38 years (mean = 12.2 years). METHODS: Standardised
      questionnaire completed and returned within a one-week period. RESULTS: Teachers
      viewed a wide range of behaviours as bullying, but significantly more agreed that
      some items (e.g., 'Threatening people verbally') were bullying than agreed others
      were (e.g., 'Leaving people out'). Teachers expressed generally negative
      attitudes towards bullying and bullies, and were generally sympathetic towards
      victims, although sympathy diminished with increasing length of service.
      Teachers, regardless of length of service, were not confident in their ability to
      deal with bullying and 87 per cent wanted more training. Significantly more
      teachers felt responsible for preventing bullying in the classroom and playground
      than outside of school. CONCLUSION: School psychologists must consider teachers'
      views about many aspects of the problem of bullying if they are to devise optimum
      strategies for tackling it.

PMID- 9254133
TI  - Steady state enzyme velocities that are independent of [enzyme]: an important
      behavior in many membrane and particle-bound states.
AB  - The popular paradigm for biological education in kinetics involves descriptions
      that are appropriate for soluble enzymes. Derivations seldom present the
      assumptions on which the fundamental parameter of these kinetics, the site rate
      constant, is based. This omission can create difficulty for understanding
      situations where the assumptions are invalid. Membrane- and particle-bound
      enzymes systems provide several examples. In fact, biological organisms show
      macroscopic design and enzyme expression levels which suggest utilization of
      alternative kinetic mechanisms. The role of substrate affinity and enzyme
      inhibitors is greatly altered, with correlated impact on biomedical and
      biotechnological designs. Enzymes may perform functions such as isolation of cell
      contents from the environment, an action that is usually reserved for membranes.
      These properties can be mimicked but never perfectly replicated in purified
      systems. This presentation provides a description of some of these behaviors for
      membrane- or particle-bound enzymes, using an approach that is closely correlated
      with the manner in which steady state enzyme kinetics are typically presented.

PMID- 9254134
TI  - Hammerhead ribozymes with a faster cleavage rate.
AB  - A hammerhead ribozyme that was previously reported to have a rate of chemical
      cleavage 10-fold faster than that of conventional hammerheads was analyzed in
      greater detail. Although originally found as a bimolecular hammerhead assembled
      through helices I and II, fast cleavage was observed in hammerheads in the more
      conventional helix I-helix III form, provided the sequence of helix I of teh fast
      hammerhead was preserved. Mutations indicted that the fast rate of cleavage was
      due to the presence of both the U1.1-A2.1 and A1.2-U2.2 base pairs. The faster
      rate of cleavage was due to a small increase in the activation entropy of the
      reaction. In addition, we confirmed previous reports that increasing the length
      of helix I by greater than five base pairs inhibits cleavage slightly and have
      uncovered a similar effect in helix II.

PMID- 9254135
TI  - [Towards a new model of the family physicians/pharmaceutical industry
      relationship].

PMID- 9254136
TI  - [The evaluation of women's health promotion services: the internal client, the
      external client].
AB  - OBJECTIVES: To find the opinion of internal and external customers of the Women's
      Health Promotion Services; to obtain information about the perceptions and
      suggestions of both midwives and users of the service. DESIGN: An observational
      study of the qualitative evaluation of a service provided in Primary Health Care,
      through an open questionnaire to midwives and focus groups with users. SETTING:
      Health Area 4 in the Community of Valencia. PARTICIPANTS: 15 midwives from Health
      Area 4, 3 groups of women using the Pregnancy Follow-up Programme and 3 groups
      from the Programme of Integrated Care for climacteric women, coming from two
      Health Districts, one urban and one rural. MAIN RESULTS: For midwives,
      coordination with general practitioners was better in the urban setting, and with
      Family Planning Centres in the rural one. Absence of team work with
      gynaecologists, and gynaecologists' failure to value midwives' work, were
      identified as problems. CONCLUSIONS: Different patterns for the organisation and
      use of women's health promotion services were identified between the urban and
      rural setting. The problems of coordination identified by the midwives are not
      perceived as such by the service's users, who evaluated as satisfactory the
      Primary Care services received.

PMID- 9254137
TI  - [The changes of physician in an adult population at an urban health center].
AB  - OBJECTIVE: To describe, quantify and analyse the phenomenon of a change of
      doctor. DESIGN: An observational, descriptive and retrospective study. SETTING:
      The Torrero-Este Health Centre in the urban periphery of Zaragoza, attending a
      population of 20,433 people. PATIENTS: 268 people of both sexes, between 16 and
      87 years old and users of the Health Centre, who requested a change of doctor
      between 1990 and 1995. MEASUREMENTS AND MAIN RESULTS: The study's variables were
      taken from the patients' clinical records; and each patient was interviewed to
      analyse the situation before and after the change. After excluding 50 for various
      reasons, there were 218 patients left. The patient profile was: women 61.7%,
      active population 57.8%, and under 60 years old 78%. Those who attended most
      often and put forward problems with their doctor as the reason for changing their
      doctor, nevertheless continued being the most frequent attenders after the
      change. There were differences (p < 0.05) in personal treatment and attendance
      between doctors who "donated" patients and doctors who "received" them, and also
      in the reason for the change and the number of consultations. CONCLUSIONS: In the
      context of the quality of services provided, we thought that changes in doctor
      expressed some kind of uneasy. This study had the double benefit of being an
      indicator of quality of care and of enabling the centre's health professionals to
      know what the flow of patients between the different clinics was, which may help
      to improve the model of clinical interview.

PMID- 9254138
TI  - [Chronic patients at home. A descriptive and survival analysis at 2 years after
      the introduction of a home care program].
AB  - OBJECTIVES: To describe the group of chronic patients cared for at home and the
      frequency of visits, and to analyse their survival at two years. DESIGN: A
      longitudinal, descriptive study. SETTING: Raval Nord Health District, Barcelona.
      PATIENTS AND OTHER PARTICIPANTS: All the 646 patients registered as chronically
      ill at home during the first two years of a programme of home care (May 1994 to
      1996). MEASUREMENTS AND MAIN RESULTS: First, a descriptive analysis of the main
      characteristics of this population group was made, which showed that 66.6% were
      women and that its average age was 81 (SD, 11 years). Less autonomy meant a
      greater number of visits (p < 0.0001), both by the doctor and nursing staff.
      Nursing visits were mainly to attend bed-sores and Diabetes Mellitus. Loneliness
      was the greatest underlying reason for social workers' visits. CONCLUSIONS: This
      was a very aged population group, with high mortality and requiring on-going home
      care. Autonomy was a good predictor both of the frequency of visits and of these
      patients' survival time.

PMID- 9254139
TI  - [A comparison of 2 clinical laboratory methods in the diagnosis of bacterial
      vaginosis].
AB  - OBJECTIVE: To determine the sensitivity, the specificity, and positive and
      negative predictive values of two laboratory methods used to diagnose bacterial
      vaginosis; Gram stain and the Gardnerella vaginalis culture, in comparison with
      the clinical sings of vaginal discharge; homogeneous secretion, pH > 4.7,
      positive amine test and the presence of clue cells. DESIGN: A prospective,
      comparative and crossover type. SETTING: This study was carried out in the Health
      Center "Dr. Jose Castro Villagrana" SSA, situated in Tlalpan, Mexico City. From
      January, 1992 to July, 1996. PARTICIPANTS: 3,142 women, from 16 to 55 years old
      with cervicovaginitis diagnosis, without previous treatment and sexual active
      life history. RESULTS: By means of clinical criterion (33.1%), it was diagnosed
      1,041 women with bacterial vaginosis. Statistical differences were not found
      between the culture and Gram stain in the presence or no-presence of bacterial
      vaginosis diagnosed by clinical criterion (p = 0.33) The clue cells were the best
      predictor of bacterial vaginosis. CONCLUSIONS: The differences between both
      methods analysed were minimal and they didn't have statistical value so that, it
      is proposed the Gram stain as diagnostic method of bacterial vaginosis based on
      factors like speed, reproductiveness and low cost.

PMID- 9254140
TI  - [The application of risk strategy to a maternal-child program at a health
      center].
AB  - OBJECTIVES: The overall objective is to prioritize health care for women and
      children at higher social risk. DESIGN: Intervention study. SETTING: An urban
      health centre. PATIENTS: Women and children using a programme for mothers and
      infants at greater social risk. Infant health (IH): immigrant children, low
      social and economic level and conflictual family relationships. Family planning
      (FP) and young adult (YA): previous abortion, low social and economic level,
      immigrants. Pregnancy monitoring (PM): pregnancies in women under 20, immigrants,
      unwanted pregnancy. Vaccinations: living in an area of social risk, child of
      immigrants. INTERVENTIONS: 1) Preferential focus on risk groups, specific markers
      in records and archives. 2) Checking attendance at appointments and recouping. 3)
      Early referral to the social worker (and midwife in risk pregnancy). 4) Analysis
      of reasons for leaving programme and improving access. MEASUREMENTS AND MAIN
      RESULTS: The number of people with a greater risk criterion. CONCLUSIONS: The
      follow-up procedures of the mother and child programme, specific to those at
      higher social risk, are useful for recouping those who leave the programme and
      for positive discrimination in the care delivered to these groups.

PMID- 9254141
TI  - [Hypertension in elderly persons: prevalence, knowledge, treatment and control].
AB  - OBJECTIVE: To assess the prevalence of hypertension, systolic isolated
      hypertension, knowledge about hypertension, pharmacologic treatment and control
      of hypertension in an elderly population. DESIGN: Cross-sectional survey,
      observational. PLACE AND PARTICIPANTS: Interview performed on a random sample of
      elderly community dwelling people 65 years and over stratified by age and sex,
      living in Leganes during 1990 (n = 1180). METHOD AND MAIN RESULTS: Information
      was collected at the elderly's homes with two interviews and a physical exam
      including blood pressure measurements. Two criteria were used for the analysis of
      hypertension: 1) WHO and 2) JNC V. In the study, hypertension was defined as
      elevated blood pressure according to the criteria and/or pharmacologic treatment
      for hypertension at the time of the interview. CONCLUSION: Prevalence of combined
      hypertension among the elderly in Leganes is in the range of values observed in
      other studies undertaken in Spain and abroad. Elderly's knowledge about their
      hypertensive condition is high and physicians' choice of antihypertensive
      treatment seems adequate. The level of control achieved depends on the criteria
      used and although subject to improvement, is similar to the one observed in other
      countries.

PMID- 9254142
TI  - [The validity of 6 indirect methods for assessing drug treatment compliance in
      arterial hypertension].
AB  - OBJECTIVE: To validate six indirect methods, which were simple and easy to apply
      in clinical practice, of identifying patients who did not comply with drugs
      treatment for hypertension. DESIGN: A prospective study based on two visits to
      patient's home. SETTING: rural health centre at Calpe, Alicante. PATIENTS: 174
      patients (58 men and 116 women) were included. They were chosen at random from
      the centre's records of hypertense patients. MEASUREMENTS AND MAIN RESULTS:
      Compliance was assessed by the method of a surprise counting of pills in the
      patient's home. Patients who had between 80 and 110% compliance were defined as
      compliant. The six indirect methods validated were: communication of self
      compliance (CS), attendance at appointments (AA), doctor's judgment (DJ),
      information about the illness (II), hypertension control (HC) and the Morisky
      Green test (MG). II was the most sensitive (81.9%). CS reached the highest
      specificity (93.4%), the best positive predictive value (81.8%) and the best
      concordance index (kappa, 0.26). CONCLUSIONS: II and CS are the indirect methods
      with the best validity indicators and could be used together to assess compliance
      with drugs treatment for hypertension.

PMID- 9254144
TI  - [A record form for the follow-up of diabetes I and II].

PMID- 9254143
TI  - [Helicobacter pylori and gastroduodenal pathology: its pathogenesis, diagnosis
      and therapeutic guidelines].

PMID- 9254145
TI  - [Homeopathy].

PMID- 9254146
TI  - [How should the drug prescription be?: efficacious and safe, of course;
      efficient?, also].

PMID- 9254147
TI  - [Insomnia at a mental health center].

PMID- 9254148
TI  - [The technical requirements for submitting manuscripts].

PMID- 9254150
TI  - [The attitudes to and needs for education on HIV infection among primary care
      health professionals].
AB  - OBJECTIVE: To evaluate the attitudes, knowledge and training needs for primary
      care health professionals (PCP) dealing with HIV/AIDS infection. DESIGN: An
      observational, crossover study. SETTING: primary care: health districts in the
      Ciutat Vella health area of the city of Barcelona. PARTICIPANTS: 34 nursing
      professionals and 32 general practitioners. INTERVENTIONS: A validated
      questionnaire, which was self-administered, anonymous and filled in under
      supervision during October 1994. MEASUREMENTS AND MAIN RESULTS: Everyone answered
      a 20-question multiple choice test of knowledge and a 5-point Likert-type
      attitudes scale with 10 items. The PCP overall displayed: insufficient scores on
      the test of knowledge, on positive attitudes, on the difficulty of asking about
      risk practices if the reason for consultation is unrelated, on safety in
      handling, and need for training. CONCLUSIONS: Half the PCP displayed a level of
      theoretical preparation in need of improvement. Their positive attitudes and the
      clear need for more training on the question make it very likely that our PCPs
      would take advantage of training programmes. The situation in areas with less
      prevalence of the infection might well be different.

PMID- 9254151
TI  - [The validity of therapeutic utility and intrinsic value as indicators of drug
      prescription quality: an analysis of treatments in cases of the common cold].
AB  - OBJECTIVE: To determine the validity of intrinsic value and therapeutic utility.
      DESIGN: The medicines prescribed in a random sample of 50 cases of common cold
      from each health centre evaluated were classified according to their intrinsic
      value (ordinal classification using five categories) and therapeutic use
      (dichotomized classification based on their intrinsic value). Patients with
      immunodeficiency or underlying pathology (COPD, cardiopathy, diabetes) were
      excluded. Each of the generic and non-specific indicators were studied to
      determine sensitivity and specificity for detecting problems in the rational
      prescription of medicines. SETTING: A representative sample from 8 primary care
      centres in the Murcia region. MEASUREMENTS AND MAIN RESULTS: The operative
      replies curve for intrinsic value revealed that this indicator was of little use
      in evaluating the quality of prescription. CONCLUSIONS: The low validity of the
      generic prescription indicators suggests that systems to monitor quality based on
      a specific focus (linking the prescription to the disease treated) should be
      designed.

PMID- 9254149
TI  - [The outlook for Spanish primary care starting with a bibliometric analysis of
      its scientific production (1971-1994)].
AB  - OBJECTIVE: To establish the relative weight of the various kinds of primary
      health care (PHC) research collected in the IME (Spanish medical index), In order
      to determine their possible relationships with Spain's PHC model. DESIGN:
      Bibliometric analysis. PARTICIPANTS: PHC documents (1971-1994) from the IME data
      base (CD-ROM), subdivided by years, journals, themes and Autonomous Communities
      (AC). RESULTS: 3,015 studies were published, with a first phase (1970s) of under
      10 documents per year, a second (1980s) with a big increase and a third (1990s)
      of stagnation. Of the 117 journals containing studies, Atencion Primaria gave a
      home to almost 58% (60% after 1984). CONCLUSIONS: PHC research production has
      stagnated recently, though the journal Atencion Primaria has maintained its
      undisputed leadership position. The clinical model predominant in Spanish
      medicine is generally followed.

PMID- 9254152
TI  - [Tobacco dependence in primary care: the opinion of professionals in the
      Guadalajara Health Area].
AB  - OBJECTIVE: To find the views and approach of primary care professionals in this
      Health Area to questions referring to restrictions on tobacco consumption,
      possibilities of intervention and resources devoted to monitoring tobacco
      dependency. DESIGN: A crossover study using an anonymous self-administered
      questionnaire with closed replies. SETTING: Primary care professionals from the
      Guadalajara Health Area. PARTICIPANTS: Medical, nursing and other professional
      staff (361 people), with an 86.1% reply rate. MEASUREMENTS AND MAIN RESULTS:
      90.7% thought it was a good idea that tobacco consumption was legally regulated,
      although only 54.3% of non-smokers and 49.7% of doctors were in favour of
      extending the law. 37.5% of doctors and 19.5% of nurses (at the expense above all
      of non-smokers) were in favour of prioritizing care for non-smokers. Over 85%
      considered useful or very useful the introduction of methods to combat dependency
      in Health Centres and among health staff. CONCLUSIONS: There is a broad consensus
      on restricting tobacco consumption in determined places and applying methods in
      primary care to facilitate giving up tobacco. A critical attitude to the state on
      its tobacco policy was noted.

PMID- 9254153
TI  - [Dementias in the primary care setting].
AB  - OBJECTIVE: To study the epidemiological, demographic, social and family, and
      clinical variables of the population suffering dementia in our health district.
      DESIGN: A retrospective evaluation of medical records. SETTING: A rural health
      district. PATIENTS: All those patients with a diagnosis of dementia in 1995.
      MEASUREMENTS AND RESULTS: The evaluation was based on primary care medical
      records. The prevalence of dementia in the over-65s ranged, according to the
      population group, between 1.29 and 5.19 per 100 inhabitants. 90.2% of patients
      with dementia remained living at home. Their average age was 79.8 (SD, 7.4). 57%
      had Alzheimer's disease. 40% were in advanced stages of the disease (stage III
      and IV). Only 26% of the patients were referred to Neurology in 1995. 35% of the
      patients took no medication for their dementia. 45.6% were included in a home
      care programme. The main carer was the son or daughter in 47.8% of cases.
      Expectation of life from when dementia was diagnosed was 5.53 (SD 4.64) years.
      Patients with dementia died in their own homes in 47% of cases, the main cause of
      death being infection. CONCLUSIONS: In our rural environment most patients with
      dementia remained with their families. In most cases the aetiological diagnosis
      of dementia could be made from primary care.

PMID- 9254154
TI  - [The evaluation of evening hours in a primary care pediatrics office].
AB  - OBJECTIVE: To know about the preference for the evening hours in the primary care
      pediatric consults. DESIGN: A crossover, observational and prospective study.
      SETTING: Pediatric consult at a health center in the town of Irun, Bidasoa
      District (Guipuzcoa). PARTICIPANTS: The mothers or companions (171) of the coming
      children. MEASUREMENTS AND MAIN RESULTS: It was asked to the mothers coming to
      the consult about their preferences for the hour. The children were divided into
      three groups: younger than 3 years, 3 to 5 and older than 5. Then, it was taken
      into account the demand of each group. Projecting the results of the poll on the
      demand, the children older than 3 prefer the evening hour and between the younger
      (who represent nearly the half of the pediatric consults), the 50% prefer the
      morning, and the other half, the evening. There are not significant differences
      comparing the children from 3 to 5 years to the older than 5. There are
      significant differences, instead, between the children younger than 3 and any of
      the two groups of children older than 3: with the group from 3 to 5 (p < 0,01),
      with the older than 5 (p < 0,05) and with the older than 3 as whole (p < 0,01).
      CONCLUSIONS: If it would be wanted to adapt the hour to their preferences, it
      would be necessary to making enable the morning hour for the children younger
      than 3, and the evening consults for the older.

PMID- 9254155
TI  - [An evaluation of the protocols of the CME program. Do they satisfy the criteria
      for the working out of clinical protocols?].
AB  - OBJECTIVE: To evaluate the protocols published in the journal Formacion Medica
      Continuada (FMC) since its appearance. DESIGN: An evaluation study. SETTING: The
      journal FMC in Primary Care. PARTICIPANTS: Clinical protocols (11) published by
      the journal, and the people who have composed them. INTERVENTIONS: An evaluation
      based on the criteria for composing clinical protocols proposed by Saura et al.
      MAIN RESULTS: Overall these proposals complied with 56.9% of the proposed
      criteria. None of them (0%) complied with all the norms that a protocol must
      meet. On analysing independently each criterion, the following were satisfied in
      all the protocols evaluated: the designation, index of pages, definition of the
      problem and bibliography. The protocol for COPE in Primary Care satisfied 75% of
      the criteria and was the protocol which complied with most criteria. The battered
      child protocol satisfied 41.66% of the criteria and was the protocol satisfying
      the least number of criteria. CONCLUSIONS: These are good protocols, in that
      overall they satisfy a large part of the proposed criteria, despite the fact that
      these are demanding criteria. However they can and must improve.

PMID- 9254156
TI  - [New vaccines in medicine: the outlook].

PMID- 9254157
TI  - [The SICAP listing: a poor instrument for coding in primary care. Sistema de
      Informacion de Centros de Atencion Primaria].

PMID- 9254158
TI  - [Adverse reactions and drugs: the wrong title and content].

PMID- 9254159
TI  - [Taking the arterial pressure during consultation].

PMID- 9254160
TI  - Estimating workforce and training requirements for nephrologists through the year
      2010. Ad Hoc Committee on Nephrology Manpower Needs.

PMID- 9254161
TI  - NIH workshop on the role of dietary supplements for physically active people.
      Bethesda, Maryland, June 3-4, 1996.

PMID- 9254162
TI  - Nutrition and HIV infection. 2nd International Conference under the aegis of the
      Society Francophone de Nutrition Enteral et Parenterale. Cannes, France, 23-25
      April 1997. Abstracts.

PMID- 9254163
TI  - Passive retrograde cerebral perfusion during routine cardiac valve surgery
      reverses middle cerebral artery blood flow and reduces the risk of stroke.
AB  - BACKGROUND AND AIMS OF THE STUDY: Cerebral complications constitute a major
      source of morbidity and disability after cardiac valve surgery. These may be the
      result of macroembolization (air/debris) or inadequate perfusion pressure. In an
      attempt to reduce the incidence of cerebral vascular accident (CVA)/transient
      ischemic attack (TIA), we have routinely performed three minutes of passive
      retrograde cerebral perfusion (PRCP) on all valve cases. Here, we retrospectively
      determined our perioperative (0-30 day) incidence of CVA/TIA. METHODS: In all
      cases, the extracorporeal circuit consisted of an ascending aortic cannula and
      either one two-stage or two single-stage venous cannulae. Three minutes of PRCP
      was instituted in all cases upon discontinuation of anterograde cardiopulmonary
      bypass (CPB) via a shunt distal to the heart/lung machine between the arterial
      and venous cannulae. Mean systemic blood pressure was maintained at 60 mmHg with
      Neo-Synephrine. Central venous pressure never exceeded 25 mmHg. In 10 cases,
      transcranial Doppler ultrasonography (TCD) was used to assess middle cerebral
      artery (MCA) blood flow. In total, 209 consecutive valve procedures with PRCP
      (group A) were compared with 164 consecutive valve procedures with no PRCP (group
      B). All data were compared using Fisher's exact probability test. The incidence
      of CVA/TIA was also compared with published retrospective and prospective data.
      RESULTS: TCD demonstrated blood flow reversal in the MCA after a minimum of 30 s.
      The incidence of CVA/TIA was 0% (0/209) in group A, and 2.4% (4/165) in group B
      (p = 0.0386). The incidence of CVA/TIA in published retrospective data is 0.7
      3.8% and 4.8-5.2% in prospective data. CONCLUSIONS: We have demonstrated in 209
      consecutive valve cases that, upon discontinuation of CPB, routine three-minute
      PRCP not only reversed MCA blood flow, but also reduced the incidence of
      neurologic events.

PMID- 9254164
TI  - [New prospects in the clearance of pulmonary edema].

PMID- 9254165
TI  - [The role of the pulmonologist in pulmonary infection].

PMID- 9254166
TI  - [Maximum static respiratory pressures in adults. The reference values for a
      Mediterranean Caucasian population].
AB  - The aim of this study was to establish reference values for PImax and PEmax for
      the Mediterranean adult population. Male and female individuals between 18 and 83
      years old meeting the criteria for consideration as references and residing in
      the metropolitan area of Valencia were assigned by decades to six subgroups, each
      containing at least 20 men and 20 women. PEmax was obtained from the point of
      maximum expiration (residual volume) and PImax was the point of maximum
      inspiration (total lung capacity). The cohort, which finally included 264
      subjects (129 men and 135 women), was separated a priori by sex for data
      analysis. The following types of variables were studied: sociological
      (employment, educational level and exercise), biometric (age, height and weight)
      and spirometric results. A linear correlation analysis was performed for each
      pair of variables and a Kolmogorov-Smirnov test of normality was performed. In
      order to check the accuracy of PImax and PEmax readings, intra-individual
      variability was determined by performing three consecutive procedures over 3 days
      in 39 randomly selected individuals (18 men and 21 women). Significant inter-day
      and inter-test effects for respiratory pressures were thus ruled out. Predictive
      equations were worked out using a simple linear model including all predictive
      variables and eliminating weaker variables in a stepwise manner. Mathematical
      goodness of fit was assessed by a coefficient for multiple determinations (R2);
      also determined were the estimated standard error and statistical significance.
      We also compared observed and estimated values and the behavior of residual
      values in terms of their independence, normality and homoscedasticity. Reference
      limits were established by defining percentiles. The equations finally arrived at
      for men were as follows: PImax (-cmH2O) - 1.03 x Age + 0.59 x Weight + 133.07,
      PEmax (cmH2O) - 1.31 x Age + 263.12. The equations for women were PImax (-cmH2O) 
      0.64 x Age + 125.18, PEmax (cmH2O) - 0.57 x Age + 0.65 x Weight + 116.26.
      Agreement with the usual references (the Black and Hyatt equations) was analyzed.

PMID- 9254167
TI  - [The prognostic factors for early mortality and for total or partial gammagraphic
      resolution in venous thromboembolic disease].
AB  - Our objective was to investigate possible factors implicated in either early
      death from or scintigraphic resolution of pulmonary embolism. To that end we
      conducted a retrospective study of 116 patients with either a high likelihood of
      pulmonary thromboembolism (PTE) diagnosed by scintiscan or with a fair
      probability of PTE by scintiscan accompanied by a positive phlebograph. The
      images were taken upon admission, at 7 days, 10 days and 6 months. The factors
      analyzed were age, sex, trauma, immobility, surgery, obesity, hemiplegia, venous
      insufficiency, cardiopulmonary disease, neoplasia, chest X-ray and ECG
      alterations, D(A-a)O2 and size of perfusion defects upon admission and 7 to 10
      days later. We performed single-variable analyses and multiple logical regression
      analyses using perfusion defect at 6 months as the dependent variable. The early
      mortality rate (13%) was higher in patients with neoplasms, a larger alveolar
      arterial index and greater perfusion defects upon admission. Scintiscans became
      normal in 28%. Multivariate analysis to predict total or partial resolution at 6
      months showed that size of perfusion defects at 7 to 10 days was the best
      predictive factor. A cutoff point was calculated by analyzing the ROC for this
      factor. Thus, when the defect at 7 to 10 days was equal to or greater than 1
      segment, the probability of residual defects remaining after 6 months was twice
      as great (sensitivity 83%, specificity 57%). In conclusion, early death was more
      likely in PTE patients with neoplasms, larger defects upon admission and greater
      alveolar-arterial difference. Scintigrams showed resolution 6 months after
      admission in 28%. The size of perfusion defects 7 to 10 days after admission was
      the factor that best predicted total of partial resolution at 6 months.

PMID- 9254168
TI  - [Cytohistological agreement of fine-needle transthoracic lung puncture-aspiration
      (FNTLPA) in malignant lesions].
AB  - To assess agreement between cyto-histological results and fine needle aspiration
      (FNA) biopsy of malignant pulmonary lesions, and to study the relation with type
      of lesion. specimen and impact on patient management. Retrospective study of FNA
      performed over the past 4 years if a biopsy was available (obtained by fiberoptic
      bronchoscopy, thoracotomy or biopsy of extrapulmonary organs) for comparison. We
      recorded overall agreement (OA) and agreement by type of disease or neoplasm
      (DA). Also studied were the features of the lesion, the puncture technique and
      material obtained in function of agreement. Eighty samples were available for
      comparison. OA was 58.7% (K = 0.17). DA was good for epidermoid carcinoma (87%, K
      = 0.64) and poor for adenocarcinoma (87.5%, K = 0.30). The lowest agreement was
      for undifferentiated large cell carcinoma (10.3%, K = 0.07). In such cases FNA
      specimens were not useful for classifying 61.5% of adenocarcinomas and 21.6% of
      epidermoid carcinomas. Cyto-histological inaccuracy was clinically significant,
      however, in only 3 (3.7%) patients. Lesions for which diagnosis was consistent
      were larger in size (4.6 +/- 2.2 versus 4 +/- 1.6 cm, p = NS), were nearer to the
      visceral pleura (1.5 +/- 2.3 versus 2 +/- 2.2 cm, p = NS) and tended to have been
      sampled with the guidance of computerized tomography (65% versus 35%), although
      this did not affect the features or amount of material obtained. We found poor OA
      for adenocarcinoma and undifferentiated large cell carcinoma. Although
      disagreement was clinically significant in only 3.7% of cases, the implications
      indicate that the specificity of the technique should be improved, above all in
      small cell carcinomas. We observed no differences as to type of lesion or
      specimen obtained that might predict interpretive difficulties.

PMID- 9254169
TI  - [Community-acquired pneumonia (CAP) with hospital treatment. The value of the
      clinical picture and complementary exams in predicting its etiology].
AB  - We studied 162 patients with community-acquired pneumonia admitted for hospital
      treatment, in order to determine the utility of clinical and ancillary
      examinations for predicting etiology and guiding the most appropriate empirical
      treatment. Acute first appearance of symptoms, purulent expectoration, chest
      sounds indicating lung condensation, pleuritic chest pain and leukocytosis over
      12,500/ml were statistically significant in differentiating typical pneumonias
      from those with atypical behavior patterns. The last two features were the most
      relevant according to multivariate analysis. We conclude that careful taking of
      case histories and basic blood testing continue to be relevant and must not be
      considered anachronistic for the differential diagnosis of community-acquired
      pneumonias.

PMID- 9254170
TI  - [The evaluation of lung vascular compliance by the dobutamine stress test in
      patients who are candidates for extensive lung resections].
AB  - This prospective descriptive study evaluated the utility of dobutamine in
      studying pulmonary vascular compliance in patients with lung neoplasms who are
      high risk candidates for lung resection. Seventeen consecutive patients meeting
      one of the following inclusion criteria were enrolled: FEV1 < 60% of theoretical
      value, FVC < 65%, residual volume > 130%. postoperative predictive FEV1 < 1,000
      ml or PaO2 < 70 mmHg breathing room air. A Swan-Ganz catheter was inserted in the
      right side 24 h before surgery. The following data were recorded: heart rate
      (HR), mean pulmonary artery pressure (PAP), cardiac output, pulmonary vascular
      resistance (PVR) and arterial blood gas readings. Measurements were taken as
      follows: a) with the patient at rest breathing room air; b) after infusion of
      dobutamine 10 micrograms/kg/min; c) 30 min after breathing room air, and d) after
      surgery. Eleven of the 17 patients underwent pneumonectomy (5 left sided and 6
      right sided). Bi-lobectomy was performed in 3 patients, segmentectomy was
      performed in 1 and lobectomy in 1. One patient did not undergo surgery because
      PAP was over 34 mmHg at baseline and did not decrease after oxygen
      administration. Dobutamine administration was associated with a significant
      increase in cardiac output (p < 0.001) and PAP (p < 0.05), with a significant
      decrease in PVR (p < 0.05), indicating good pulmonary vascular reserve in our
      cohort. No patient suffered serious complications in the postoperative period and
      all were released from the hospital. There were no complications related to
      dobutamine perfusion. We conclude that the study of pulmonary vascular function
      with dobutamine in high risk candidates for extensive lung resection may be a
      simple method for evaluating pulmonary vascular compliance before surgery,
      although its possible usefulness still remains to be determined.

PMID- 9254171
TI  - [The diagnosis and treatment of community-acquired pneumonia. SEPAR. Sociedad
      Espanola de Neumologia y Cirugia Toracica].

PMID- 9254172
TI  - [The importance of creating adult cystic fibrosis units].

PMID- 9254173
TI  - [Primary pulmonary nodular amyloidosis].
AB  - Localized nodular pulmonary amyloidosis is a very rare condition. We report the
      case of a man with an upper left lobe mass measuring 8 cm and a nodule measuring
      3 cm at the same site. Both were detected by chance in radiologic images.
      Neoplasia was suspected and diagnosis was made by thoracotomy and lung biopsy.
      After two years of follow-up, the patient remains asymptomatic and the radiologic
      images are stable, with no clinical or analytical evidence of systemic
      amyloidosis or dysproteinemia.

PMID- 9254174
TI  - [Pulmonary torsion of the right superior lobe: an unusual complication secondary
      to surgery].
AB  - Pulmonary torsion is a serious complication consisting of the rotation of the
      pulmonary parenchyma upon its vascular pedicle. Torsion is usually related to
      lung surgery and may lead to death. Early diagnosis allows for the rapid
      treatment that is essential for preventing death and decreasing associated
      complications.

PMID- 9254175
TI  - [A giant-cell tumor with rib location].

PMID- 9254176
TI  - [The quality of life related to health in pneumology].

PMID- 9254177
TI  - [Lingual tuberculosis: apropos a clinical case].

PMID- 9254178
TI  - [Contaminated esparto fibers: the cause of extrinsic allergic alveolitis].

PMID- 9254179
TI  - [The usefulness of the isolation of Cryptosporidium in the respiratory secretions
      of HIV-infected patients].

PMID- 9254180
TI  - Castles in the air?

PMID- 9254181
TI  - [The sociomedical problems in the work of flight instructors].
AB  - Study of medicosocial problems of pilot instructors revealed their sufficiently
      good health status which, however, was liable to decrease because of augmenting
      stress due to poor social protection and difficulties in the training of young
      pilots. Early professional aging of this group is obvious; it is caused by
      deterioration of the health status and by destruction of motivation coupled with
      the pension policy pursued with regard to military pilots. Pilots engaged in the
      training of young specialists are in need of sociopsychological monitoring and
      regular and comprehensive measures aimed at health maintenance and
      rehabilitation. We consider that at present these problems can hardly be solved
      because of insufficient attention of the state organizations and governmental
      structures to the present-day situation in aviation. The authors propose measures
      for regulating the labor of pilot instructors and prophylactic, therapeutic, and
      rehabilitation measures aimed at reducing the impact of psychogenic occupational
      factors.

PMID- 9254183
TI  - [Medical care standards in modern public health].

PMID- 9254182
TI  - [The economic problems of regional public health].

PMID- 9254184
TI  - [Public health at the municipal level].
AB  - The purposes of health protection and fortification in various sociums and
      conditions of attaining these purposes may differ at various levels (federal,
      regional and municipal) of the society organization. At the municipal level the
      fortification and protection of population health may be regarded as the chief
      idea, aim, and criterion of the optimal functioning and development of a socium
      of the given level, reflecting the measure of efficacy of providing the immediate
      vital activity of the population. The task of social management is as follows:
      the share of the national output, created by the socium, is to be distributed so
      that it were possible for this socium to permanently recreate and maintain at a
      certain qualitative level its labor resources--the major energy potential of the
      socium, and adequately provide and guarantee human rights as the main value of
      the society. A logistic model of the management structure ensuring population
      health at a municipal level is presented. For health control and for attaining
      this aim it is necessary to transfer the maximum of legal functions to the
      municipal level of society administration. It is desirable that every citizen,
      and not only administration, be involved in the reformation of the society as
      regards health protection, and that the citizens be personally interested in this
      process.

PMID- 9254185
TI  - [Economic mechanisms in decreasing the level of hospitalizations].
AB  - Increase of the role of primary health care and decrease of hospitalizations is a
      pressing medical and economic problem. However, rather often it is beneficial for
      a medical institution to hospitalize a patient. In order to create stimuli for
      decreasing the level of hospitalization, medical institutions are to have a share
      in the economy due to non-hospitalization. Proper validation of the share of the
      resultant economy is needed to realize this principle.

PMID- 9254186
TI  - [The international classification of the sequelae of diseases in modern public
      health].

PMID- 9254187
TI  - [The hospitalization of patients with acute surgical diseases of the abdominal
      organs].

PMID- 9254188
TI  - [Improvement in the activities of the system of obligatory medical insurance].

PMID- 9254189
TI  - [Physicians and the population on the reforming of public health (based on
      sociological research data)].
AB  - A sociological analysis of the opinions of physicians and population on public
      health reforms was carried out during the period of active introduction of
      obligatory medical insurance in Russia, that is, in July-August 1994 and 1995. A
      total of 4000 questionnaires distributed among the population and 2500 among
      physicians were analyzed using the random cluster and typological proportional
      sampling. The paper presents statistical data disclosing the opinion of the
      population and physicians on the process of introducing obligatory medical
      insurance as the priority improvement in the activity of outpatient health
      centers and on other reforms in public health. Analysis of public opinion
      demonstrated the difficulties of the present period and the reserves in improving
      the reformation of public health which may be used to ensure guaranteed volume of
      medical care rendered to the population.

PMID- 9254190
TI  - [An analysis and the aspects of the introduction of plastic cards into medical
      insurance in Russia].

PMID- 9254191
TI  - [Experience in raising the qualifications of physicians in a region].

PMID- 9254192
TI  - [The history of the opening of the clinical institutes of Moscow University].

PMID- 9254193
TI  - [The Faculty Therapeutic Clinic of St. Vladimir University: the formation of the
      Kiev Scientific Center of Ukrainian Therapy. I. The founding of the clinic. Its
      first professor--F. S. Tsytsurin (1844-1857)].

PMID- 9254194
TI  - [S. F. Vol'skii--Russian historian of medicine of the 1830s to 1840s].

PMID- 9254195
TI  - [Zemstvo physician V. V. Khizhniakov (on the 125th anniversary of his birth)].

PMID- 9254196
TI  - [Iakov Alekseevich Chistovich].

PMID- 9254197
TI  - [The first optometrist of Russia L. N. Gassovskii].

PMID- 9254198
TI  - [The prevalence of digestive organ diseases and the organization of specialized
      care].
AB  - Analysis of 5942 case histories of inpatients and 15,482 case histories of
      outpatients helped reveal the morbidity structure with regard to diseases of the
      digestive system and assess these diseases incidence in the urban and rural
      population of different age and sex. The incidence of diseases of the biliferous
      duct was found to be 45.6, of peptic ulcer 21.4, and of pancreatitis 14.2 per
      1000 population for the urban population and 7.2, 20.2, and 2.3/1000,
      respectively, for the rural population. The age of the urban patients is most
      often 40 to 49, that of the rural ones 50 to 59 years. Among surgical inpatients
      the share of cases with involvement of the biliferous duct was 8.8%, with
      gastroduodenal ulcer 14.1%, and with pancreatitis 6.4%. Diseases of the digestion
      organs rank fourth in the mortality structure; 92.3% of deaths are patients
      hospitalized in emergency.

PMID- 9254199
TI  - [Basic trends in the development and realization of state scientific and
      technical programs in the field of preventive medicine].
AB  - Reviews the state research and technological programs on priority trends in
      medical science. The programs are aimed at improving the nation's health. The
      emphasis in these programs is laid upon prophylactic medicine and the
      sociohygienic approach, underlying the health status of children and adults in
      the country.

PMID- 9254200
TI  - [The quality and efficiency of medical care and medical services as philosophical
      and medical problems].

PMID- 9254201
TI  - [Medical service and the methodology of expertise (formalizing medical care)].

PMID- 9254202
TI  - [The organizational and economic aspects of the introduction of obligatory
      medical insurance].
AB  - The principal stages in transition to obligatory medical insurance are discussed.
      Such transition is to be carried out with due consideration for the readiness of
      this or that territory to it, and necessitates a rational arrangement of the
      network of public health institutions and the optimal number of medical staff
      corresponding to planned scope of work; choice of a value for financing medical
      care with consideration for certain requirements of, primarily, statistical and
      standard well-being; estimation of prices for medical services with consideration
      for labor consumption for this or that type of work using mainly the parameters
      for the entire branch, as well as the local standards for labor; distribution of
      means to subdivisions and individual specialists in accordance with the scope,
      complexity, and quality of services rendered.

PMID- 9254203
TI  - [The characteristics of actuarial calculations for voluntary medical insurance].
AB  - Presents methods of mathematical validation of agreements on voluntary medical
      insurance. Reduction coefficients are used for determining the onset of the
      insurer's responsibility after a certain number of invalidity days. The reduction
      coefficient is regarded as a probability that the insured person recovers not
      later than by a certain date, and the sequence of these coefficients as function
      of distribution of the course of invalidity. Use of the actuarial estimations for
      validating different aspects of voluntary medical insurance helps specify the
      probable payments and provide the financial stability of insurance companies.

PMID- 9254204
TI  - [The necessity for structural changes and their medico-economic trends in public
      health].
AB  - Discusses the new socioeconomic conditions in public health, which imply higher
      requirements to the use of resources and to their quality. Emphasizes that a
      physician of a general profile promotes the development of such tendencies, the
      realization of which, in turn, is conductive to other structural changes
      reflecting the changes in the population health and in changing need in medical
      care.

PMID- 9254205
TI  - [The results of a comprehensive evaluation of the health status of the
      population, of public health resources and of the socioeconomic status of the
      territories of the Russian Federation].
AB  - Population health in the Russian Federation was assessed over the course of 5
      years using a universal method with ranking of territories according to Euclidian
      distance, which is a variant of cluster analysis. The same method was used in
      study of the ratio of territories as to their provision with public health
      resources and some resultant socioeconomic parameters. Under condition of the
      socioeconomic crisis involving the whole country, the population health rapidly
      reacted to changes by developing new and progress of the existing negative
      tendencies, which led to shift of some territories, particularly of the Northern
      ones, in the ranked series. As a rule, there are more problems with population
      health at territories with more strained socioeconomic situation.

PMID- 9254206
TI  - [Optimization of the activities of the treatment and prevention hospital
      institutions in Tver' Province].
AB  - Assesses the actual level of bed fund use in various types of hospitals and for
      various profiles of the bed fund, as exemplified by Tver' Province [correction of
      district]. Presents the tentative estimation of the possible reduction of the bed
      fund, increase of the efficacy of its exploitation, redistribution of the
      releasing resources, and more extensive outpatient medical care.

PMID- 9254207
TI  - [Conceptual modelling of urban medical care].

PMID- 9254208
TI  - [Experience in the sociological study of the reasons for the refusal of the
      population to consult for medical care].

PMID- 9254209
TI  - [Regional characteristics in the development of and structural changes in public
      health].

PMID- 9254211
TI  - [The problems of medical insurance in the article by James A. Rice "The new
      social contract in the countries of the former Soviet Union"].

PMID- 9254212
TI  - [The transformation of the public health system in the USA in the context of the
      global reform process].

PMID- 9254210
TI  - [Medical personnel: the scientific and practical aspects (the current status of
      the problem)].

PMID- 9254213
TI  - [The history of the development of the public health system in the European North
      under extreme socioeconomic conditions].

PMID- 9254214
TI  - [The scientific hygiene schools of Russia at the end of the 19th-the start of the
      20th centuries (a comparative analysis)].

PMID- 9254215
TI  - [Pasteur stations in Byelarus and their role in the development of
      microbiological research].

PMID- 9254216
TI  - [The evaluation of the health of the working-age population].

PMID- 9254217
TI  - [Means for the rational utilization of the bed resources under obligatory medical
      insurance].
AB  - Presents a multivariant system of rational use of the bed fund used in Samara
      Province [correction of district]. This system helped preserve the scope of
      hospital aid rendered to the population in 1993-1995 which was planned by the
      district program of obligatory medical insurance, despite cutting down about
      5,000 beds in premises previously adjusted for therapeutic needs and old
      premises.

PMID- 9254218
TI  - [Public health reforms in the CIS countries].
AB  - The health status of the population has been deteriorating at virtually all
      territories of the former USSR during the last decade. The author considers that
      cooperation within the framework of the Coordination Committee of the CIS
      countries, aimed at creating a universal organ rendering methodological and
      practical assistance to member countries, already through with the disintegration
      stage and striving to reintegration, is the most effective approach to public
      health reformation.

PMID- 9254219
TI  - [General medical (family) practice in the system of primary medical health care].

PMID- 9254220
TI  - [Improvement in the legal support of the epidemic health well-being of the
      population in the Russian Federation].
AB  - The study is devoted to the problem of scientific validation for the development
      of legal basis of sanitary and epidemiological welfare of the population of
      Russia. Many-year complex expert and analytical studies of the valid and newly
      created laws in this sphere helped design a conceptual model of the development
      and improvement of the system of sanitary legislation.

PMID- 9254221
TI  - [The role of the audit in the system of obligatory medical insurance].
AB  - Presents the fundamentals of applying audit to the system of obligatory medical
      insurance. Auditory check-up of the funds of obligatory medical insurance
      revealed waste of money, detected its causes, and proposed approaches to
      correcting it. Use of auditory service is a condition indispensable for improving
      the reliability of obligatory medical insurance functioning.

PMID- 9254222
TI  - [The problems in the information support for the activities of an outpatient
      polyclinic institution in the system of obligatory medical insurance].

PMID- 9254223
TI  - [Public opinion on the questions of obligatory medical insurance].
AB  - Presents the results of investigation of public opinion about the development of
      obligatory medical insurance (OMI) system. The majority of respondents consider
      that introduction of OMI should be paralleled with improvement of the quality of
      medical care free of charge and its preservation. Opinions about OMI differ
      within a wide range in different sociodemographic groups and indicate that
      purposeful differentiated ideological activity is needed to propagate the idea of
      OMI.

PMID- 9254224
TI  - [Higher medical education in the USA].

PMID- 9254225
TI  - [Scientific fallacies in medicine (the historical aspect)].

PMID- 9254226
TI  - [The teaching of chemistry in the Medical Department of Moscow University in the
      18th century].

PMID- 9254227
TI  - [Russian Action (the history of Russian medicine abroad)].

PMID- 9254228
TI  - [The medical workers of the hospital bases at the rear in World War II].

PMID- 9254229
TI  - [The Omsk Institute of Epidemiology and Microbiology in 1941-1945].

PMID- 9254230
TI  - [The medicine of Belorussia during the occupation (1941-1944)].

PMID- 9254231
TI  - [A century of the Bryansk Society of Physicians].

PMID- 9254232
TI  - [Medical and health organization in the building of the Amur railroad (1891
      1913)].

PMID- 9254234
TI  - [Physician and public figure V. A. Stradomskii].

PMID- 9254233
TI  - [The history of immunoprophylaxis in Belorussia].

PMID- 9254235
TI  - [Chronic nonspecific lung diseases in the structure of general population
      morbidity].
AB  - Analysis of the level and time course of mortality due to chronic nonspecific
      diseases of the lungs based on the death certificates issued by physicians in
      1990-1993 in Omsk Province [correction of district] revealed a tendency to an
      increase of this parameter to as much as 48.4 per 100,000 population, and still
      higher in the rural regions. The mortality of the rural population is 2-3 times
      higher than in town. Chronic nonspecific pulmonary diseases are frequently
      concomitant with other diseases, in 75% cases with cardiovascular diseases; the
      majority of the cases are latent, and, hence, the true social significance of the
      diseases is unknown. The share of chronic nonspecific pulmonary diseases among
      other causes of death increases with age; it is higher in men than in women (7.5
      and 5.4% in town and 20 and 15% in the country, respectively). Chronic bronchitis
      predominates among chronic nonspecific diseases of the lungs causing death, being
      responsible for 75 to 81% lethal cases; bronchial asthma ranks second (6.5-15%),
      other diseases are rare.

PMID- 9254237
TI  - FDA seeks help in evaluating consequences of therapeutic interchange.

PMID- 9254236
TI  - [Drug abuse problems among senior high-school students of Stavropol'].
AB  - Characterizes the prevalence of use of alcohol, narcotic and toxic agents and
      tobacco smoking among the older schoolchildren in the Stavropol district in 1991
      and 1994. The prevalence and motivation of alcoholization, tobacco smoking, and
      narcotization of adolescents and schoolchildren are analyzed on a large
      representative scope of material. The regularities in the development of harmful
      habits and time course of their progress are disclosed and the unfavorable
      tendencies are shown as regards the most socially hazardous types of
      narcotization of schoolchildren--alcoholization and narcotization.

PMID- 9254238
TI  - Changes in hospital ownership proliferate, with uncertain effect on communities.

PMID- 9254239
TI  - [Risk factors and cancer prevention].

PMID- 9254240
TI  - [Esophageal cancer: its epidemiology, risk factors and prevention].

PMID- 9254241
TI  - [Risk factors for gastric cancer].

PMID- 9254242
TI  - [The epidemiology, risk factors and prevention of liver cancer].

PMID- 9254243
TI  - [The search of risk factors for pancreatic cancer: practice, patience and
      paradigms].

PMID- 9254244
TI  - [Risk groups for colorectal cancer].

PMID- 9254245
TI  - [The epidemiology, risk factors and prevention of anal cancer].

PMID- 9254246
TI  - [The gastric mucosal barrier. Introduction].

PMID- 9254247
TI  - [The resistance of the superficial gastric epithelium to aggression].

PMID- 9254248
TI  - [The role of prostaglandins in the defense of the gastric mucosal barrier].

PMID- 9254249
TI  - [Leukocyte-endothelium interaction: inflammation and gastric damage].

PMID- 9254250
TI  - [The effect of nitric oxide on the regulation of gastric blood flow].

PMID- 9254251
TI  - [Growth factors in the defense of the gastric mucosal barrier].

PMID- 9254252
TI  - [Mucus and bicarbonate secretion in the gastric mucosal barrier].

PMID- 9254253
TI  - [The immune system and the defense of the gastric mucosal barrier].

PMID- 9254254
TI  - [Immune disorders in acute pancreatitis and principles of immunocorrecting
      therapy].
AB  - An expert system of diagnosis of the immune disorders types according to Gell and
      Coombs classification was for the first time applied in the examination of 63
      patients with different forms of an acute pancreatitis (AP). The individualized
      schemes of the immunocorrecting therapy depending on the type of disorder and the
      grade of the intoxication syndrome present were elaborated.

PMID- 9254256
TI  - [Reflux gastritis due to Helicobacter pylori as the cause of unsatisfactory
      results of cholecystectomy].
AB  - In 85.8% of patients with cholelithiasis (CL) the reflux-gastritis was revealed,
      of whom in 71.4% caused by Helicobacter pylori. In 80% of patients the positive
      effect achievement is guaranteed by the early accomplishment of cholecystectomy
      and an active conduction of rehabilitation measures in early postoperative
      period.

PMID- 9254255
TI  - [Clinical effectiveness of the use of liposomes with antibiotics and ecterocide
      in purulent-inflammatory thoracic and abdominal complications].
AB  - The liposomes with antibiotics and ectericide were applied in the complex of
      treatment of 120 patients with purulent-inflammatory diseases of respiratory and
      digestive systems. Prominent curative effect of the liposomes with antibiotics
      selective application was established.

PMID- 9254257
TI  - [Clinical and morphological aspects of Helicobacter pylori invasion in reflux
      esophagitis].
AB  - The mucosal biopsies morphological investigation of the lower third of esophagus
      were conducted for Helicobacter pylori detection in 43 patients with reflux
      esophagitis. Helicobacter pylori were detected in 66.7%, gastric metaplasia-in
      83.3% of patients. Helicobacter pylori plays an important role in reflux
      esophagitis pathogenesis. Surgical treatment is indicated if the combined
      antireflux and antibacterial therapy is ineffective.

PMID- 9254258
TI  - [Intravenous catheter embolism].
AB  - Ethiology, diagnosis, prognosis and the way of the intravenous catheter embolism
      (ICE) elimination are depicted. The results of endovascular removal of foreign
      bodies from the cardiac chambers and main vessels are presented. Recommendations
      concerning the patients with ICE conducting are given.

PMID- 9254259
TI  - [Dynamics of external respiration indicators after laparoscopic and open
      surgery].
AB  - The comparative evaluation of spirometric indexes restoration after laparoscopic
      cholecystectomy (LC) and open cholecystectomy was presented. Each of two groups
      consisted of 27 patients. The method of computer pneumotachometry (CPTM) using
      "ETON 01" microprocessor system was used. Functional possibilities of lungs are
      significantly higher after the LC conduction, and CPTM parameters on the third
      day are better than in patients on the 7th day after open cholecystectomy.

PMID- 9254260
TI  - [Pathogenesis and treatment of pancreatic pseudocyst and pancreatic fistula].
AB  - The functioning part of parenchyma, isolated from the organ and its duct system
      due to the presence of pancreatitis or injury is the source filling the
      pseudocyst cavity and the cause which supports the pancreatic fistula existence.
      Possibility of pancreatic pseudocyst simulation in experiment on dogs was proved.
      An experimental cyst cavity decompression was done with the help of the tunnel
      conducted via papilla between the cyst and the main duct.

PMID- 9254261
TI  - [Results of the use of perftoran for anti-ischemic protection of renal
      transplant].
AB  - Renal allotransplantation was conducted in 44 patients. Forty injured persons 20
      58 yrs. of age with brain trauma and also 4 patients with brain tumor, who have
      died in a specialized neuroreanimation department, served as donors. Control
      group consisted of 20 patients, basic one-24 patients in whom the intravenous
      perftoran infusion in 10-15 ml/kg dose was conducted additionally while the
      conditioning procedures were done. In basic group the transplants proved to be
      more functionally sufficient alike the control one.

PMID- 9254262
TI  - [Use of organ-preserving surgery in patients with renal coral-like calculi and
      chronic renal failure].

PMID- 9254263
TI  - [Indicators of cellular immunity and the level of autoneurosensitization in
      patients with cerebral palsy after transplantation of the embryonal nerve tissue
      into the brain].
AB  - According to the clinico-immunologic investigation in patients suffering a birth
      palsy it was established, that the transplantation operation into the brain of
      embryonal neural tissue (ENT) causes not only the clinical course changes of the
      disease, but also have positive influence on the immune system specific and
      nonspecific indexes. The immunity state changes after the operation were
      dependent on what side hemisphere of the great brain the ENT was transplanted.

PMID- 9254264
TI  - [Substantiation of indications for low-intensity laser irradiation in combined
      preoperative care of patients with ulcerative gastrointestinal hemorrhage].
AB  - Indications for the low-intensive laser application in preoperative procedure
      scheme were speculated on the ground of complex investigation data in 175
      patients with gastrointestinal ulcerative hemorrhage (GIUH). Indications for
      intravascular laser blood irradiation (IVLBI), for the projectional action on
      thymus, spleen and their combined application are established. For the reliable
      hemostasis guarantee the conduction of laser therapy is the most effective one.

PMID- 9254265
TI  - [Abdomino-anal resection of the rectum with the bringing down of the
      demesenterized colon into the anal canal].

PMID- 9254266
TI  - [Use of low-energy laser irradiation in patients with colorectal cancer after
      surgery].
AB  - Intravascular blood irradiation with laser was conducted in the early
      postoperative period in 32 patients with colorectal cancer with the use of
      semiconductor laser "Looch-2". It promoted the decrease of the purulent
      complications prevalence, the lowering of the thromboembolism occurrence risk,
      the diminution of the endogenic intoxication syndrome expression. Fast
      rehabilitation of patients was promoted by renewal of antitumoral resistance and
      immunity.

PMID- 9254268
TI  - [Combined and surgical treatment of cancer of the proximal stomach involving the
      lower third of the esophagus].
AB  - The experience of treatment of 197 patients with proximal stomach cancer,
      involving the lower third of esophagus, was analyzed. Surgical treatment was
      performed in 91 (46.2%) patients, combined treatment-in 106 (53.8%).
      Postoperative mortality was (17.3 +/- 2.7)%, five year survival index-(29.9 +/-
      3.2)%.

PMID- 9254267
TI  - [Immunological monitoring of patients with disseminated colorectal cancer under
      thermochemotherapy].
AB  - The basic immunological indexes were investigated in patients with disseminated
      colorectal cancer after conduction of magnetothermia and chemotherapy using
      fluorouracil. Control group consisted of 11 patients, to whom monotherapy with
      fluorouracil was prescribed. The modifying action of magnetothermia alleviates
      significantly the immunodepressive effect of cytostatic drugs.

PMID- 9254269
TI  - [Analgesia in pancreatic cancer. Achievements and perspectives].

PMID- 9254270
TI  - [Surgical treatment of morbid obesity].

PMID- 9254271
TI  - [Singlet oxygen therapy].
AB  - Physico-chemical concept of the singlet oxygen therapy application using
      photochemically sensibilized air or drinking a water, already barbaturized by an
      activated singlet oxygen of air, is adduced. Therapy technology and examples of
      its clinical application in the treatment of several pathologic processes for the
      free-radicals correction are depicted.

PMID- 9254273
TI  - [Surgical treatment of peptic ulcer associated with chronic duodenal
      obstruction].
AB  - Results of treatment of 333 patients with duodenal ulcer disease (DUD) combined
      with chronic duodenal impassability (DDI) were analyzed. Principles of surgical
      tactics choice were expounded, and indications for the operation were
      substantiated. Postoperative complications occurred in 9.3% of patients.
      Improvement of surgical results was promoted by application of an adequate
      procedure with chronic duodenal impassability correction.

PMID- 9254275
TI  - Are you $aving enough?

PMID- 9254274
TI  - [Use of quantum hemotherapy in complex treatment of aged patients with
      suppurative inflammatory diseases].
AB  - The results of different kinds of the quantum hemotherapy application in elderly
      patients with purulent-inflammatory disease of soft tissues were summarized. The
      combined laser-ultraviolet irradiation proved to be the most effective, its
      application permitted to improve significantly the results of treatment.

PMID- 9254272
TI  - [Drainage in the care of cavities].

PMID- 9254276
TI  - [Of mice and men: social impact of an emerging illness].
AB  - In response to unexplained deaths in an Indian reserve of the southwestern United
      States, a fascinating scientific investigation rapidly led to the identification
      of a new infectious syndrome, the "Hantavirus pulmonary syndrome". The health
      promotion campaign that followed was remarkable for its large scale and for the
      efficiency of its delivery, but was not well received by the people on the
      reserve. This article demonstrates that the preventive guidelines were
      incompatible with the natives' popular beliefs and that the social trauma caused
      by the intervention could have been avoided since within the Indian tradition the
      disease was already well-defined and effective preventive means had been
      developed.

PMID- 9254277
TI  - [From vocation to discipline].
AB  - This article looks at the history of nursing care in relation to modern-day nurse
      theorists' concepts of a professional nursing identity. In her discussion of the
      history of female caregivers and the nursing profession, the author attempts to
      show that by shifting nursing care from the concept of a vocation to a so-called
      scientific concept, nurses have failed to resolve their identity problem. The
      author maintains that the reason for this failure stems from the early days of
      the profession when line managers ignored the tradition of caregiving, rather
      than using it as the basic rationale of the nursing profession. This former
      tradition had caregivers using medicinal herbs, preparing home remedies,
      performing minor surgery, helping women during childbirth (midwifery),
      accompanying the dying and helping the poor. The author concludes that nurses
      would benefit from greater awareness of their profession's historical roots. This
      would in turn give them a clearer understanding of the type of services they are
      capable of delivering to the public.

PMID- 9254278
TI  - [Private practice: a choice, but what challenges!].
AB  - Recent changes in the Canadian health care system are having an impact on the way
      health care services are delivered. As a result, opportunities are opening up for
      a whole new generation of autonomous and independent nurses who choose to work
      directly with clients in a private practice setting. In part one of this two-part
      article, the author describes the main responsibilities of the nurse
      entrepreneur. Stressed are the areas of competency and the entrepreneurial spirit
      required. Administrative, professional, legal and fiscal aspects of independent
      practice are also outlined. Part two of the article focuses on the ethical
      responsibilities of the nurse entrepreneur and the regulations concerning fees,
      publicity, insurance, and office and file management. The author recommends
      keeping current on new developments and establishing a process whereby clients
      can evaluate the quality of care they receive.

PMID- 9254280
TI  - Outcomes research.

PMID- 9254279
TI  - Familial and developmental abnormalities of front lobe function and
      neurochemistry in schizophrenia.
AB  - structural abnormalities of the cerebral cortex in schizophrenia have been
      revealed by magnetic resonance imaging, although it is not clear whether these
      abnormalities are diffuse or local. We predicted that changes in cortical
      structure would result in abnormalities in biochemical markers for the glutamate
      system in post-mortem brain, and that the pattern of neurochemical abnormalities
      would be a clue to the distribution and extent of pathology. A number of studies
      have now reported increases in biochemical and other markers of glutamatergic
      cell bodies and terminals in the frontal cortex in schizophrenia. These findings
      are consistent with the presence of an abnormally abundant glutamatergic
      innervation, which may be due to an arrest in the normal developmental process of
      synaptic elimination. In the anterior temporal cortex and hippocampus there is
      evidence of an asymmetric loss of glutamate terminals, and of reduced GABA
      function, which may be secondary to the glutamatergic deficit. Glutamate cell
      body markers are spared in the temporal lobe; we argue that the loss of glutamate
      uptake sites may reflect the loss of an extrinsic glutamatergic innervation of
      the polar temporal cortex which arises from the frontal cortex. These fronto
      temporal projections may be vulnerable because they arise from a cytoarchitecture
      which has not been stabilized by remodelling during early post-natal life. There
      have been several therapeutic studies of drugs with actions on brain glutamate
      systems. Based on the glutamate deficiency theories, one approach has been to
      enhance glutamatergic function using agonists of the N-methyl-D-aspartate-linked
      glycine site. However, there are no clear therapeutic effects, and some studies
      report aggravation of positive symptoms. This might be expected if, as part of
      our post-mortem studies suggested, there is excess glutamatergic innervation in
      some brain regions in schizophrenia. There is neuropsychological evidence that
      frontal abnormalities in schizophrenia may be genetically determined. We found
      that first degree relatives of schizophrenic patients were selectively impaired
      in tests of frontal lobe function, whereas both frontal and temporal function is
      impaired in patients We conclude that the genetic predisposition to schizophrenia
      involves impaired frontal lobe function. Psychotic symptoms develop only when a
      second process results in a loss of fronto-temporal projections and leads to
      temporal lobe dysfunction.

PMID- 9254281
TI  - [The role of cellular contacts in the recovery of the ion channels of epithelial
      cell membranes].
AB  - Cationic currents in mature MDCK cells are almost exclusively due to K+ channels.
      Harvesting with trypsin-EDTA destroys 80-90% of these channels. Upon replating,
      K+ currents recover in 12-20 h, by means a process that requires synthesis of
      proteins and of RNA. In the present work we demonstrate that this restoration
      depends on a Ca2+ activated-cell contact. Thus, cells in confluent monolayers
      bathed with 1.8 mM Ca2+ have a K+ current of 343 +/- 82 pA; confluent without
      Ca2+ have only 90 +/- 12 pA (27% of control; and without cell-cell contacts
      incubated with 1.8 mM Ca2+ (subconfl+Ca2+) have 104 +/- 21 pA (31% of control).
      This demonstration that the expression of K+ channels depends on Ca-activated
      cell-attaching molecules suggests that a molecule of the type of uvomorulin is
      involved.

PMID- 9254282
TI  - [The chemotherapy of cysticercosis. The results 10 years or more after follow
      up].
AB  - Chemotherapy for neurocysticercosis was born logically because of the scant
      success of surgery, which is generally palliative, not curative. Prazicuantel is
      the only drug about which serious of more than 100 cases, and follow-up of more
      than 2 years, have been published. Its use has become universal, reason enough
      for this theme to be addressed. This paper pretends to contribute to the
      determination of its therapeutic value in the treatment of neurocysticercosis by
      means of the clinical and radiologic treatment of 50 sick persons followed up for
      from between 10 (72%) and more than 10 (28%) years. The patients had been treated
      with prazicuantel with a dose of 50 mg per kilo of body weight during 15 days;
      26% received one treatment, 58% received two, and 22%, three or more treatments.
      The patients were studied once again clinically and radiologically with computed
      axial tomography of the cranium and magnetic resonance. Biological testing was
      done only if activity-suspected cases. The results showed a rate of 68% clinical
      cures or important improvement. Emphasis is made of the 6% of cases in which the
      clinical cure process was apparent. It was confirmed that neurocysticercosis is a
      generalized chronic ailment in which evolution is achieved by means of periods of
      activity alternating with periods of recession. The employment of witnesses is
      not advised, and it is suggested for later investigation that ample series of
      cases be followed-up over long periods of time. It is insisted upon that the best
      treatment for the illness is prophylaxis.

PMID- 9254283
TI  - [Quality paradigms in medical care].

PMID- 9254284
TI  - [The beginnings of occupational medicine in New Spain during the 16th century].

PMID- 9254285
TI  - [The first school of medicine and the first university of the American continent
      in Mexico].

PMID- 9254286
TI  - [Primary spontaneous bilateral coronary dissection associated with arterial
      calcinosis].

PMID- 9254288
TI  - [Streptococcus pneumoniae. The appearance of antibiotic resistance].

PMID- 9254287
TI  - [The molecular bases of AIDS therapy].

PMID- 9254289
TI  - [The epidemiology of dementias].

PMID- 9254290
TI  - [The legal framework of artificial insemination].

PMID- 9254291
TI  - [Concepts on the treatment of patients infected with the human immunodeficiency
      virus (HIV)].

PMID- 9254292
TI  - [Juvenile myoclonic epilepsy].

PMID- 9254293
TI  - [Pain in the Guillain-Barre syndrome in children].
AB  - In Guillain-Barre syndrome (GBS) painful involvement has not been considered as a
      major clinical manifestation for diagnostic criteria among children. Was to
      evaluate whether clinical our purpose painful sensations are the main
      manifestations in pediatric patients with GBS. Twenty patients that fulfilled the
      Asbury criteria for diagnosis of GBS were studied prospectively from January,
      1992 to June, 1994. Painful sensations were evaluated considering segmentary
      level with special focus in intensity, modality, topography distribution from the
      beginning to the resolution of the paralysis and effect to analgesic therapy
      every day for the first week and weekly thereafter. Patients had a mean age of
      9.6 years (SD 5.4). Twelve patients were males and eight were females. All the
      patients but one complained of pain during some time of the course of illness,
      (19/20, 95%). At the illness onset, pain sensations were spontaneously referred
      in 12/20 (60%) of the cases, after anamnesis in 3/20 (15%) and physical exam in
      4/20 (20%). Pain distribution during acme occurred in feet, thighs and legs in
      95% of patients; back, arms and forearms in 65%, buttocks, shoulders and hands in
      35%. The highest intensity of pain took place the first week of the illness
      course, and the mean time of decreasing occurred with a median of three days
      after onset with complete resolution three weeks later. We report that pain was
      an early and main clinical manifestation of GBS in children. We suggest that pain
      must be considered as a relevant criterium for GBS diagnosis in pediatric
      patients.

PMID- 9254295
TI  - [Specialization and specialties in medicine].

PMID- 9254294
TI  - [The factors associated with a lengthy hospital stay in a third-level unit].
AB  - A descriptive, cross-sectional and retrospective design was developed in order to
      assess the frequency of patients with lengthy hospital stay (LHS) and associated
      factors at the Hospital de Especialidades, Centro Medico Nacional Siglo XXI,
      IMSS, in Mexico City from January to April, 1993. Some 2,488 patients were
      discharged during this period and 541 were selected at random. There were 23.9%
      (n = 131) of patients who had LHS, with a specific mean of 7.7 days and a total
      mean of 18 days of hospital stay compared with 5 days for those patients who did
      not have LHS. The associated factors were: patient's origin, admission
      conditions, complications, hospital infections, category and specialty of
      attending physician, delay in laboratory and diagnostic imaging exams and
      results, delay in surgical interventions, and need of outside transportation at
      time of discharge. Characteristics of patients with greater probabilities of
      having LHS are outside origin, diagnosis of malignant tumor, complications,
      hospital infections, and delay in laboratory exams and in surgical interventions.
      Some of these characteristics can be modified in order to improve LHS and quality
      of medical care. Further investigations are required to individually analyze
      these characteristics as well as the justification for LHS and its costs.

PMID- 9254296
TI  - [The bicentenary of smallpox vaccination].

PMID- 9254297
TI  - The Niagara-on-the-Lake Hypnosis Conference. August 1996. In memory of Kenneth S.
      Bowers, Ph.D. (1937-1996).

PMID- 9254298
TI  - Pandemic Influenza: Confronting a Re-emergent Threat. Proceedings of a meeting.
      Bethesda, Maryland, 11-13 December 1995.

PMID- 9254299
TI  - IIIrd European Workshop on Digestive Surgery. Brussels, Belgium, 13-14 May 1997.

PMID- 9254300
TI  - 7th International Symposium on Pediatric Neuro-Oncology. Washington, DC, May 15
      18, 1996. Abstracts.

PMID- 9254301
TI  - [Diagnostic imaging and functional tests--deglutition disorders (MRI, deglutition
      pressure)].

PMID- 9254302
TI  - Alterations of Na+ channel gating in myotonia.

PMID- 9254303
TI  - Take caution with the 'no suicide contract'.

PMID- 9254304
TI  - Remarks by Dr. Dennis H. Leverett on receiving the John W. Knutson Distinguished
      Service Award.

PMID- 9254306
TI  - [Lack of knowledge about waiting lists in health care. Reformed care guarantee
      could have the answers].

PMID- 9254305
TI  - [Medical science explains. The art of medicine understands. A new book on medical
      history from the prehistoric time to the year 2000].

PMID- 9254307
TI  - [Patients should be listed with primary care units, not with individual
      physicians!].

PMID- 9254308
TI  - [Pertussis vaccine with a component--safe and effective].

PMID- 9254309
TI  - [Worry about the IGM is not justified].

PMID- 9254310
TI  - [What anti-depressive agent is best?].

PMID- 9254311
TI  - [A serious discussion concerning p-pills is needed].

PMID- 9254312
TI  - [A lot in Alconline is missing in Medline].

PMID- 9254313
TI  - [Thyroid gland surgery in the future].

PMID- 9254314
TI  - [There are all reasons to choose an accredited laboratory].

PMID- 9254315
TI  - [Accreditation of a laboratory involves quality requirements].

PMID- 9254316
TI  - [Research laboratories can also be accredited].

PMID- 9254317
TI  - [Clinical psychopharmacology. The art of prescribing a correct dosage, and being
      able to make the patient take it].

PMID- 9254318
TI  - [Care during the initial phase of suspected myocardial infarct. Lack of knowledge
      results in deficient treatment].

PMID- 9254319
TI  - [Malignant skin melanoma a difficult clinical diagnosis. The primary management
      is often insufficient].

PMID- 9254321
TI  - [Melanocytic tumors. Liberal nevus surgery and histopathological scrutiny reduce
      mortality].

PMID- 9254320
TI  - [Delayed diagnosis of subungual melanoma. Two cases were misjudged as
      onychomycosis].

PMID- 9254322
TI  - [Sexuality--an important factor for quality of life. Who should treat erectile
      dysfunction?].

PMID- 9254323
TI  - [Liver abscess caused by Ascaris lumbricoides. Memorandum about hepatic changes
      in adopted children from developing countries].

PMID- 9254324
TI  - [Enterovirus infections in new disguise].
AB  - Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of
      small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses
      cause a number of wellknown diseases and symptoms in humans, from subclinical
      infections and the common cold to poliomyelitis with paralysis. The development
      of polio vaccines is the greatest accomplishment within the field of enterovirus
      research and the background work was awarded the Nobel prize in 1954. New
      knowledge implies that enteroviruses play a more important part in the morbidity
      panorama than was previously thought. Chronic (persistent) enteroviruses were
      formerly unknown. Serologic and molecular biology techniques have now
      demonstrated that enteroviral genomes, in certain situations, persist after the
      primary infection (which is often silent). Persistent enteroviral infection or
      recurrent infections and/or virus-stimulated autoimmunity might contribute to the
      development of diseases with hitherto unexplained pathogenesis, such as post
      polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly
      some cases of chronic fatigue syndrome.

PMID- 9254325
TI  - [From an idea to a completed drug: a process of 10-15 years].

PMID- 9254326
TI  - [A lot of irrelevance on psychoses. A more streamlined approach is needed].

PMID- 9254327
TI  - Visibility for nurses.

PMID- 9254328
TI  - Improvement committee reaps benefits.

PMID- 9254329
TI  - Nursing cutbacks and patient care.

PMID- 9254330
TI  - BIONJ: an improved version of the NJ algorithm based on a simple model of
      sequence data.
AB  - We propose an improved version of the neighbor-joining (NJ) algorithm of Saitou
      and Nei. This new algorithm, BIONJ, follows the same agglomerative scheme as NJ,
      which consists of iteratively picking a pair of taxa, creating a new mode which
      represents the cluster of these taxa, and reducing the distance matrix by
      replacing both taxa by this node. Moreover, BIONJ uses a simple first-order model
      of the variances and covariances of evolutionary distance estimates. This model
      is well adapted when these estimates are obtained from aligned sequences. At each
      step it permits the selection, from the class of admissible reductions, of the
      reduction which minimizes the variance of the new distance matrix. In this way,
      we obtain better estimates to choose the pair of taxa to be agglomerated during
      the next steps. Moreover, in comparison with NJ's estimates, these estimates
      become better and better as the algorithm proceeds. BIONJ retains the good
      properties of NJ--especially its low run time. Computer simulations have been
      performed with 12-taxon model trees to determine BIONJ's efficiency. When the
      substitution rates are low (maximum pairwise divergence approximately 0.1
      substitutions per site) or when they are constant among lineages, BIONJ is only
      slightly better than NJ. When the substitution rates are higher and vary among
      lineages,BIONJ clearly has better topological accuracy. In the latter case, for
      the model trees and the conditions of evolution tested, the topological error
      reduction is on the average around 20%. With highly-varying-rate trees and with
      high substitution rates (maximum pairwise divergence approximately 1.0
      substitutions per site), the error reduction may even rise above 50%, while the
      probability of finding the correct tree may be augmented by as much as 15%.

PMID- 9254331
TI  - Incubation temperatures affect adherence to plastic of Candida albicans by
      changing the cellular surface hydrophobicity.
AB  - The influence of cellular surface hydrophobicity on the adherence capacity to
      plastic of Candida albicans was investigated at two culture temperatures (37 and
      22 degrees C). The majority of the 42 strains studied were hydrophobic at 22
      degrees C and hydrophilic at 36 degrees C. The hydrophobic cells showed a
      consistent adherence capacity which was absent from the hydrophilic strains. The
      culture temperatures affect adherence to plastic of C. albicans by changing the
      cellular surface hydrophobicity.

PMID- 9254332
TI  - Regulation of rubratoxin-B biosynthesis: assessment of role of gamma-irradiation,
      pH and carbohydrates.
AB  - The maximum rubratoxin-B yield was obtained at pH 5.5,, and by increasing the
      initial pH to near neutrality the yield decreased for both yeast extract sucrose
      (YES) and Sabouraud dextrose yeast extract (SDYE) media, but the concentration of
      mycotoxin was higher in YES medium. The rubratoxin-B yield from Penicillium
      purpurogenium decreased with increasing gamma-irradiation, and at 1.0 kGy no
      mycotoxin was detected at any pH values. In both the unirradiated and irradiated
      P. purpurogeniium cultures, as the rubratoxin-B synthesis increased from 46 to 72
      h, the lipid content decreased. The concentration (mmoles/g dry wt mycelium) of
      puridine nucleotides in the mycelium of P. purpurogenium during growth in YES and
      SDYE media may be a factor in rubratoxin-B synthesis. An elevated NADPH/ NADP
      ratio favours fatty acid synthesis whereas a depressed NADPH/NADP ratio favours
      mycotoxin formation. The gamma-irradiation played a role in the regulation of
      rubratoxin-B biosynthesis.

PMID- 9254333
TI  - Fish consumption and the risk of myocardial infarction.

PMID- 9254334
TI  - Fish consumption and the risk of myocardial infarction.

PMID- 9254335
TI  - Fish consumption and the risk of myocardial infarction.

PMID- 9254336
TI  - Clonal relapse in Hodgkin's disease.

PMID- 9254337
TI  - Postexposure treatment of HIV.

PMID- 9254338
TI  - Postexposure treatment of HIV.

PMID- 9254339
TI  - Are advances in treatment changing views about high-risk sex?

PMID- 9254341
TI  - Upside down in the Journal.

PMID- 9254340
TI  - Melanoma after PUVA therapy for psoriasis.

PMID- 9254342
TI  - [Creutzfeldt-Jakob disease].
AB  - A most common form of human prion disease, also known as non-conventional slow
      virus diseases; Creutzfeldt-Jakob's disease is described in detail. The available
      data on the pathogenesis of the illness have recently changed and constitute a
      most exciting article of contemporary medicine. 109 cases are introduced that
      have been verified neuropathologically in Hungary until now; their summed up
      clinical data, the pathological findings and their epidemiological
      characteristics are discussed. It must be emphasized that the diagnosis of the
      illness cannot be inevitably confirmed clinically. Transplantation of organs or
      tissues of all deceased, who suffered of an illness with dementia, should be
      strictly avoided accordingly.

PMID- 9254343
TI  - [Does tonsillectomy cause any change in long-term course of IgA nephropathy?].
AB  - Tonsillectomy seems to be a logical step in IgA nephropathy owing to the frequent
      tonsillitis before the beginning and the acute exacerbations of the disease. The
      usefulness of tonsillectomy is questionable because there are only few and short
      term follow-up data after it. We followed up 35 kidney biopsy proven IgA
      nephropathy patients (25 men and 10 women) for an average of 12.2 yrs (range 7
      32) after tonsillectomy. The values of endogenous creatinine clearance, serum
      creatinine, hematuria and proteinuria were compared at regular intervals during a
      follow-up with those obtained before tonsillectomy. We considered more than
      12,000 data using 2 tailed t test. We found that proteinuria started to decrease
      significantly already 6 months after tonsillectomy (1.40 +/- 0.27 g/day before
      tonsillectomy vs 0.92 +/- 0.25 g/day after it, p < 0.05) and was significantly
      lower under follow-up. The tendency in microhematuria was similar (70.5 +/- 35.0
      million RBC/12 hours before and 14.0 +/- 6.5 million RBC/12 hours 6 months after
      tonsillectomy, p < 0.0001). Furthermore, tonsillectomy stopped gross hematuria
      appearing in the acute exacerbation of the disease in more than two-thirds of
      patients. Creatinine clearance did not change in the first 2 years after
      tonsillectomy, however, from 2.5 years after it is significant slow and continual
      decrease started (117.0 +/- 9.8 ml/min before and 106.2 +/- 10.8 mil/min 2.5 yrs
      after tonsillectomy, p < 0.05). End-stage renal failure was detected only in 4
      patients out of 35 after 10 years after tonsillectomy, in our non
      tonsillectomised control group in 8 patients out of 40.

PMID- 9254344
TI  - [The state of radiotherapy in 1996 Hungary and principles of its development].
AB  - Although the number of radiation treatments (external) fields and
      brachytherapeutic insertions) increased substantially, by 9% of a year, in
      Hungary in 1994 and 1995, about half of the patients who needed radiotherapy did
      not receive this form of treatment. The regionalization of radiotherapeutic care
      resulted in the establishment of 12 centres, with considerable discrepancies in
      infrastructural and staff conditions, characterized by presence of Western
      European conditions in 1 institution or by close to them in 3 institutions, but
      by lack of the required infrastructure or personnel in two-thirds (8) of the
      centres. To reach the minimum recommended infrastructural level, Hungarian
      radiotherapeutic care requires the following items for the 12 centres: 4
      radioprotected treatment rooms, 8 linear accelerators of dual energy, 4 low
      monoenergetic linacs/telecobalt units, 5 after-loading set-ups, 6 simulators, 6
      CT-based treatment planning systems and 6 automatic water phantoms. With respect
      to the present workload, the number of personnel in the different groups is low;
      the situation is especially problematic in newly organized or reconstructed
      centres. Furthermore, provision of radiation treatment to all cancer patients who
      need it, requires development at every level of the staff. Increases in the
      infrastructural and staff conditions of the currently existing radiotherapeutical
      centres should be the actual goal, and not the foundation of new centres. The
      most important aspects of the priority in the development of the infrastructure
      are the following: higher number of adequately trained staff, academic
      obligations (universities), change of the amortized facilities and
      supplementation of the currently empty radioprotected rooms with equipment.

PMID- 9254345
TI  - [Usage of antibiotics in hospitals].
AB  - The authors publish the results of a survey conducted among hospital records of
      patients discharged from eight inpatient's institutes between 1-31st of January
      1995 to gather information on the indications and usage of antibiotics. The
      institutes were selected from different part of the country to represent the
      hospital structure as much as possible. Data from the 13,719 documents were
      recorded and analysed by computer program. It was found that 27.6% of the
      patients (3749 cases) received antibiotic treatment. 407 different diagnosis and
      365 different surgical procedures (as profilaxis) were considered as indications
      of antibiotic treatment (total: 4450 indications for 5849 antibiotic treatment).
      The largest group of patients receiving antibiotics was of antibiotic profilaxis
      (24.56%, 1093 cases), followed by lower respiratory tract infections (19.89%, 849
      cases), uroinfections (10.53%, 469 cases) and upper respiratory tract infections.
      Relatively large group of patients belonged to those who had fever or
      subfebrility without known reason (7.35%, 327 cases) and to those who did not
      have any proof in their document indicating the reasons of antibiotic treatment
      (6.4%, 285 cases). We can not consider the antibiotic indications well founded in
      those groups of patients (every sixth or every fifth cases). The most frequently
      used antibiotics were of [2-nd] generation cefalosporins. The rate of nosocomial
      infections were found as 6.78% average. The results are demonstrated on diagrams
      and table.

PMID- 9254346
TI  - [Total cavo-pulmonary anastomosis in heart surgery for the correction of
      univentricular heart].
AB  - The total cavopulmonary anastomosis is one of the alternative surgical procedures
      which can be performed in the management of the most complicated congenital heart
      diseases. It was the first time in Hungary that this surgical management was
      performed successfully in a girl with univentricular heart, pulmonary valve
      stenosis, malposition of the great arteries, who was operated on palliative
      procedure previously.

PMID- 9254347
TI  - [Sir Joseph Lister (1827-1912). On the 100th anniversary of his honorary
      membership in the Hungarian Medical Faculty as well as the millennium of the
      founding of Hungary (896)].

PMID- 9254348
TI  - [Instruction for Ph. D. in oncology in Hungary, its development and advancement
      with the support of the European Foundation for Advanced Education (Tempus)].

PMID- 9254349
TI  - [Helicobacter pylori and peptic ulcer].

PMID- 9254350
TI  - [Apoptosis in the regulation of immune processes and in the pathogenesis of
      autoimmune diseases].
AB  - Programmed cell death (mainly apoptosis) is involved in all fundamental processes
      of the immune system. Furthermore, apoptosis is essential for elimination of
      autoreactive lymphocytes and is, therefore a mechanism to guarantee self
      tolerance. There are several genes directly implicated in the regulation of
      lymphoid apoptosis. However, certain mouse strains expressing the defective
      mutants of those genes exhibit immunological dysfunctions resembling human
      autoimmune disease conditions. Thus, further analyses of such animal models could
      facilitate the better understanding of immunopathological abnormalities
      developing in humans.

PMID- 9254351
TI  - [Assessment of myometrial invasion in endometrial cancer by transvaginal
      ultrasonography].
AB  - Transvaginal ultrasound was used in 52 women to characterise endometrial cancer
      with respect to myometrial invasion according to International Federation of
      Gynaecologist and Obstetricians (FIGO) recommendations for surgical staging of
      endometrial cancer. Endometrial cancer was diagnosed on the basis of dilatation
      and curettage and the degree of invasion was evaluated preoperatively by
      transvaginal ultrasound. The ultrasound data were compared to macroscopic finding
      of the uterine specimen and to histopathology. Evaluation with transvaginal
      sonography was accurate in 46 of 52 cases (accuracy 88%, sensitivity 86%,
      specificity 90%, positive predictive value 92%, negative predictive value 83%).
      Cervical tumor extension was correctly diagnosed in seven of ten women in which
      it was present. Transvaginal ultrasound seems to be a reliable method for
      assessing tumor invasion. This non-invasive method could be included as an
      important tool in te establishment of individualised treatment program in case of
      women with endometrial cancer.

PMID- 9254352
TI  - [Microsporum infections in Hajdu-Bihar County].
AB  - Mycotic infections caused by Microsporum canis occurred in 237 cases between 1983
      1995 in Hajdu-Bihar county. The disease accumulated seasonally up during the
      beginning of summer and the end of autumn, in particularly. Children and young
      people had often got microsporiasis. Women patients seemed to be more frequent
      than men. The disease in many cases, appeared on all members of families. A main
      factor in spreading of pathogen were apparently healthy Persian cats. Only few
      cases could be observed in child-communities on the occasion of screening. The
      oral antimycotics-griseofulvin, terbinafine-combined with local ones proved
      efficacious in the treatment of scalp microsporia and extensive skin infections.
      Local antimycotical unguents/creames and solutions resulted acceptable effects in
      the therapy of localized microsporiatic symptoms. Cooperation between
      dermatologists, epidemiologists and veterinaries is needed for successful
      prevention.

PMID- 9254353
TI  - [Utilization of antibiotics according to most frequent indications at Hungarian
      hospitals and results of surveys].
AB  - Antibiotic utilisation of 8 Hungarian hospitals was analyzed examining the case
      histories of patients who were discharged between January 1 and 31, 1995. Usage
      of antibiotics in the most frequent indications is reported in this paper.
      Majority of the prescriptions for the treatment of upper and lower respiratory
      tract infections were broad spectrum beta lactams. Higher rate of penicillin
      usage was found only in tonsillitis cases. Besides II. generation cephalosporins
      (22.7% of 730 prescriptions), beta-lactamase inhibitor + aminopenicillin
      combinations (13.4%) and III. generation cephalosporins (9.5%) considerable
      quantity of aminoglycosides (14.9%) and quinolones (9.5%) were found in
      pneumonia. Relatively high rate of aminoglycosides in the treatment of lower
      respiratory infections is inconsistent with therapeutic guidelines in force. Co
      trimoxazol and quinolones were most frequently prescribed for the treatment of
      lower urinary tract infections. Traditional urodesinficients were on the first
      place only at one hospital. Treatment of frequently occurring nosocomial
      infections was compared with those of community acquired at the same site. There
      was not significant difference in the utilisation rates of the most of antibiotic
      groups regarding place of disease acquisition. 44% of the 1373 prescriptions for
      perioperative profilaxis was indicated for clean operations where benefit of
      antibiotic administration is questionable. Duration of antibiotic profilaxis was
      more than 48 hours in 59% of prescriptions. Drugs most frequently used for
      perioperative profilaxis were II. generation cephalosporins (23.7%), metronidazol
      (16.7%), aminoglycosides (9.6%) and III. generation cephalosporines (9.6%). The
      authors compare their results to the literature. They suggest the setting up of
      "infection control committees" to organise the antibiotic policies in hospitals.

PMID- 9254355
TI  - [Do not neglect our national literature either!].

PMID- 9254354
TI  - [Comparative analysis of diagnoses by the referring family physician and the
      hospital admission committee in ambulatory patients at an internal medicine
      department].
AB  - The objectives of the present study were, as follows: 1. To what rate do the
      primary care doctors refer their patients to the regional internal medicine
      emergency department? 2. What sort of problems are the reasons of the referring?
      3. To what extent are the opinions of the referring doctors confirmed or reviewed
      by the specialists? 4. What rate of the referred patients are admitted or
      discharged after the urgent consultations and-or interventions. 5. What kind of
      additional tests were used by the institutional caregivers in order to make
      accurate diagnoses? 6. What was the fate of the unaccepted patients? Data were
      collected in the patient document archive of the First Dept. of Medicine of the
      Albert Szent-Gyorgyi Medical University, Szeged, Hungary. Each patients'
      referring notes and inpatient charts between September 15th, 1995 and January
      15th, 1996 were studied in a retrospective way. Upon the results of the study, it
      was concluded, as follows: The primary care doctors referred their patients with
      right orientation diagnosis to the emergency department in 70% of the cases.
      45.8% of the referred pts. were admitted to the internal inpatient ward. The
      agreement of the referring and discharge diagnoses was greater (85.7%) among the
      admitted patients as compared to the unaccepted ones (56.8%). 14% of the referred
      pts. were referred to other specialists by the internists. On the basis of the
      results the actual messages of the study for an under- and postgraduate medical
      teaching group, and for the health care politicians are discussed in the paper.

PMID- 9254356
TI  - [Sub-intensive management of acute gastrointestinal hemorrhages: possibilities,
      pitfalls and hopes].

PMID- 9254357
TI  - [Tumors of the papilla of Vater--diagnostic and therapeutic dilemmas].
AB  - Benign and malignant tumors of papilla Vateri are rare diagnoses in the
      endoscopic practice. Sixteen patients with benign and 22 cases of malignant
      tumors are presented. In all of them endoscopic cholangiopancreatography with or
      without papillotomy followed by biopsy and operation in 13 cases was performed.
      Biopsy confirmed the endoscopy in 71%. Adenomyosis, supposed by endoscopy was
      proved by repeated histology in only 2/9 cases although invasive component of the
      tumor was found in 3/9 patients at operation underlying precancerous nature of
      this entity. Among 5 cases of villous adenoma one developed malignant alterations
      during 4 years of follow-up. Biopsy was not more effective after papillotomy than
      without it, and 5-7 days of delay for recovery of thermic lesion did not
      ameliorate success rate of histology. For malignant diseases surgical therapy
      should be considered if staging of tumor and general condition of the patient
      permits. In unresectable cases endoscopic palliation (papillotomy or polypectomy
      with or without drainage) can increase survival. In patients with benign tumors
      operative endoscopy followed by regular ultra-sonography and endoscopy seems to
      be necessary.

PMID- 9254358
TI  - [The female athletes' triad: eating disorders, amenorrhea, osteoporosis].
AB  - The study provides a summary of the most important features of eating disorders,
      amenorrhoea and osteoporosis jointly called the female athletes' triad.
      Considering the seriousness of the various symptoms, different branches of sport
      are affected to a different degree, which could be explained by the
      predispositioning risk factors being featured differently. The weight of the
      problem is indicated by the fact that eating disorders in female athletes show a
      15-62%, while amenorrhea a 3.4-66% prevalence. There is no similar comprehensive
      figure concerning osteoporosis. Though various studies make the connection
      unambiguous, there can be no doubt about the urgency of further tests with
      respect to screening, therapy and prevention, as well.

PMID- 9254359
TI  - [Expression of macrophage markers in childhood and adult Langerhans histiocytosis
      (LCH)].
AB  - In the diagnosis of the Langerhans cell histiocytosis several monocyte and
      macrophag markers have been tested in the recent years. We compared the
      expression of macrophage and lymphoid markers in childhood and adult type
      Langerhans cell histiocytosis. Ten childhood and 11 adult cases were tested using
      paraffin sections of biopsy samples. We have examined 6 markers: the S-100,
      Lysozyme, CD68 macrophag and the CD1a, CD4, HLA-DR lymphoid markers. We have
      found that the CD68 marker was more frequently positive than the other examined
      macrophag markers, and proved to be almost as reliable as the recently discovered
      CD1a. The most interesting result was that the expression of the markers was
      different in the childhood and adult type of the disease. On the basis of our
      experience the possibility arise that the phenotype of the childhood and adult
      type of the Langerhans cell histiocytosis is different.

PMID- 9254360
TI  - [Urinary calcium excretion. (Normal values for urinary calcium/creatinine ratio
      in Hungary). Multicenter study].
AB  - Metabolic bone disorders have attracted increasing attention in Hungary due to
      their significant impact on public health care. Measuring urinary calcium
      excretion is the first step in the biochemical assessment of bone metabolism.
      Fasting urinary calcium corrected by creatinine excretion is widely used all over
      the world. The aim of the present study was to establish standard methods and
      normal values for the calcium/creatinine ratio in Hungary. Twenty-four centers
      specializing in metabolic bone diseases participated in the study. Urine
      standards were sent out to these centers for calcium and creatine determinations.
      Based on the collected data, methods were corrected in order to achieve similar
      results for the standards. In the second phase of the study, the normal values
      for calcium/creatinine ratio were determined in SI units based on the data from
      1846 healthy subjects (age 20-80 yrs) including 944 females and 902 males. The
      normal value for females was 0.438 +/- 0.391 (means +/- SD), and 0.395 +/- 0.352
      for males, respectively (p < 0.03). The ratio increased with age in both sexes.
      The highest values were observed between 60-64 years in women and 70-74 years in
      men, respectively. After this peak, the calcium/creatinine ratio decreased. The
      values before and after 45 years of age were significantly different both in
      women (0.37 +/- 0.36, vs. 0.52 +/- 0.41, p < 0.001; and men (0.32 +/- 0.23, vs.
      0.47 +/- 0.45, p < 0.001). The use of this distinction is recommended in the
      everyday practice.

PMID- 9254361
TI  - [The favorable effect of humic acid based complex micro-element preparations in
      cadmium exposure].
AB  - The authors have studied the effect of consumption of a humic acid based complex
      microelement preparation (potassium, magnesium, iron, zinc, manganese, copper,
      vanadium, cobalt, molibden, selenium bound to humic acids) for six weeks (10 ml
      daily) on the biological exposure indices (blood and urine cadmium levels) and
      clinical laboratory parameters (liver and kidney tests, blood picture) of men (n
      = 18; 39.7 +/- 10.4 years of age;) working in cadmium exposure for 8.3 +/- 5.0
      years. The initial mean blood and urine cadmium levels of the non-smoking
      subjects was twice higher than that of the non-smoking male controls living in
      the same urban area (n = 35), and significantly correlated with the length of
      exposure. Their mean serum alanin-aminotransferase, gamma-glutamyl-transferase,
      creatinine, uric acid and urinary N-acetyl-beta-D-glucosaminidase levels were
      significantly higher than that of the controls. After the six-week treatment
      blood cadmium level, activity of serum alanin-aminotransferase, serum uric acid
      and urinary protein concentrations decreased significantly, the abnormal serum
      iron levels normalized. According to this results, the absorption of cadmium
      decreased on the effect of the complex microelement supplementation and the
      adverse laboratory changes attributable partly to cadmium exposure improved.
      Therefore humic acid based complex microelement supplementation is recommended as
      an effective tool for prevention and health protection in occupational cadmium
      exposure as well as for smokers known to be considerably burdened by cadmium.

PMID- 9254362
TI  - [Centenary of the invention of bronchoscopy].

PMID- 9254363
TI  - [Kornel Scholtz, M. D. (1871-1962)].

PMID- 9254364
TI  - [New concepts in the therapy of diabetic cardiopathies].
AB  - Most reasonable cause of diabetic cardiopathy might be the impaired energy fuel
      supply and metabolism producing inevitably a hypotic condition and needing
      myocardial cytoprotection. Under diabetic conditions glucose disposal of the
      heart muscle-decreases, but working myocardial cell remains penetrable for
      glucose even in the absence of insulin. Therefore, it is worth to stimulate
      aerobic glycolysis to protect diabetic heart from frequent ischaemic events
      induced by diabetic late complications, since fatty acids oxidation wastes more
      oxygen than glycolysis for ATP production. Trimetazidine has an original
      cytoprotective mode of action reducing oxygen demand without altering heart
      activity. Consequently, trimetazidine protects structure and functions of the
      ischemic myocardial cell. On the other hand, glycation and altered turnover of
      proteins play also an important role in the development of diabetic cardiopathy.
      Consequently, not only trimetazidine but aminoguanidine could also reduce the
      development of alterations in diabetic cardiopathy inhibiting the glycation of
      proteins. Finally, calcium antagonists are also very usefull in myocardial
      cytoprotection of the diabetic heart, according to the altered cellular calcium
      regulation and a calcium overload which play the main role in the development of
      diabetic cardiopathy.

PMID- 9254365
TI  - [Experience with endoscopic diagnosis and treatment of acute biliary
      pancreatitis].
AB  - Acute biliary pancreatitis may be a grave illness with a fatal outcome in some
      instances. Its etiology is unclear so far. The diagnosis is difficult even with
      the help of conventional diagnostic methods and the most up to date imaging
      techniques. The most sensitive method among laboratory investigations is the
      elevation of ALT (serum alanine transferase) while endoscopic
      cholangiopancreatography has the highest accuracy rate of invasive diagnostic
      procedures. There is a chance of spontaneous remission in cases with mild
      symptoms while invasive measures-endoscopy or surgery-are needed in cases with
      grave symptoms. In the present study we evaluate 23 of our cases.

PMID- 9254366
TI  - [Possibilities to increase the efficacy of growth hormone therapy in Turner
      syndrome].
AB  - The authors gave an account of the results of the first two years treatment of
      Turner's syndrome with growth hormone. They used the international reference
      standards to evaluate the treatment aimed at promoting the growth of girls having
      Turner's syndrome. The applied the projected final height method to predict
      height. Their results proved that their treatment which improved growth had
      favourably accelerated height velocity and increased the projected final height,
      which they hoped to lead to adult final height. They dealt with the trend of
      costs/benefit rate of treatment which improved the growth in children with Turner
      syndrome and on its basis they emphasized the importance of individual treatment.
      The continuous control of growth hormone treatment not only purported to the
      improvement of the efficiency of the therapy but also makes possible to avoid
      raising exaggerated expectations in the parents.

PMID- 9254367
TI  - [Cases of multiple tumors in our clinic].
AB  - Between 1989 and 1994, 719 patients had been treated with tumours at the
      Department of Surgery, Teaching Hospital of Semmelweis University Medical School,
      Budapest, Multiple tumours were found in 53 cases (7.37%), 49 of these being
      duplex and four triplex form. In men colorectal carcinoma was the most frequent
      while in women synchrone and metachrone breast cancers. Simultaneous breast
      tumors were most often found in senior patients (mean age 72.7) and metachrone
      ones at younger age (first tumor at 54.8 and the second one at 65.4 years of age,
      the following time being 10.6 years). Colorectal and gynecological tumours
      appeared with breast cancer in 5 cases. Regional colorectal tumours developed in
      five patients after radiotreatment of the pelvis. Familiar accumulation of
      colorectal cancer occurred in 4 cases. Lynch syndrome developed in 2 patients.
      The role of genetical factors is known in this group of illness, and they need to
      be screened. In this study the metachrone cancer in women occurred most
      frequently and only these patients received oncological treatment. The more
      effective treatment is supposed to enhance the number of multiplex tumours in
      which etiological factors also can play a role likewise mutagen effects of the
      first cancer therapies. The importance of collecting and processing these data is
      to referre to those risks, which should be considered in our everyday diagnostic
      work and postoperative care in these groups of patients.

PMID- 9254368
TI  - [Aortic regurgitation caused by quadri-cuspid aortic valve].
AB  - Authors report the surgical treatment of a rare malformation of the aortic valve
      associated with coronary artery stenosis. The aortic valve had a supernumerary
      cusp which was revealed intraoperatively. The supernumerary cusp appeared to be
      similar in size to the three other. Surveying the literature it is stated, that
      the number of similar entities are about 50 in number. Autopsy findings note,
      that the prevalence is about 0.008-0.012%. During the past 25 years, in aortic
      valve replacement cases such entity could have not been explored. The possible
      significance of the entity lays in--that without rheumatic or degenerative origin
      in the life span (above 40 years of age) it may lead to severe regurgitation
      leading to functional deterioration.

PMID- 9254370
TI  - [Correlations between control of therapeutic drug use and contemporary patient
      care].

PMID- 9254369
TI  - [Electronic medical consultation].
AB  - This short paper introduces various preprogrammed and knowledge-based decision
      support methods. Fundamentals of case-based reasoning, clinical algorithms,
      statistical decision theory, decision trees, rule-based systems, causal networks
      and mathematical models that can be used to store and manipulate medical
      knowledge are reviewed. This brief introduction can serve as a guide to papers
      illustrating the use of different methodologies in clinical practice.

PMID- 9254371
TI  - [Nitrogen monoxide (NO) in the function of the gastrointestinal tract and the
      liver].
AB  - This review is concerning with the endothel derived relaxing factor (EDRF)
      discovered in 1980 and identified as NO in 1987 in the function and activities of
      the gastrointestinal tract and the liver. It is of importance, that NO seems to
      basic mediator of the so called nonadrenerg-noncholinerg inhibitory innervation
      of the bowel, and also takes part in the regulation of mucosal blood supply and
      secretory function. In portal hypertension elevated cGMP is found in the urine,
      as evidence of increased nitrogen oxide synthase (NOS) activity. NO may act both
      as hepatoprotective and cytotoxic factor in the free radical reactions of several
      liver disease.

PMID- 9254372
TI  - [The effect of the delivery method on the mortality of very low birth weight
      infants in case of breech presentation].
AB  - The authors have investigated the data of 1009 neonates born from breech
      presentation in the I. Department of Obstetrics and Gynecology of Semmelweis
      Medical School between January 1., 1990 and December 31., 1995. The frequency of
      caesarean section in this group was 75.5%. In the subgroup of very small neonates
      (those under the birthweight of 1500 grams) caesarean section was performed in
      71.4%. In this group 73.8% of the neonates were alive on the 28th postpartum day,
      as opposed to 37.7% in the group spontaneously delivered. The difference proved
      to be significant in the group weighing between 750 and 1249 grams.
      Intraventricular haemorrhage was also more frequent in the group spontaneously
      delivered. The difference was not significant in the groups under 750 grams and
      between 1250 and 1500 grams birthweight. Based on their investigation the authors
      conclude, that in the group of fetuses whose estimated birthweight is predicted
      to be between 750 and 1250 grams by ultrasound examination, perinatal mortality
      and morbidity rates in breech presentation can be improved by performing
      caesarean section.

PMID- 9254373
TI  - [Synchronous surgical removal of esophageal and pulmonary cancer by endoscopic
      mucosectomy and video-assisted lobectomy through minimal thoracotomy].
AB  - Authors report a case of a 75 year old, male patient suffering from an early
      stage squamous esophageal cancer and a synchronous adenocarcinoma of the lung.
      The patient was operated on simultaneously at the same setting: the esophageal
      tumour was taken out by endoscopic mucosectomy, whereas the pulmonary cancer was
      removed by video assisted minimal thoracotomy. The definitive histological
      diagnosis was: squamous cell cancer (muscular mucosal cancer) (pT1) of the
      esophageal lesion and adenosquamous cancer (pT2) of the lung. Authors draw
      attention on the significance of the early diagnosis of malignant tumours, and in
      this case minimally invasive endoscopic procedures can be successfully performed.

PMID- 9254374
TI  - [Prenatal genetic diagnosis of type I autosomal dominant polycystic kidney
      disease].
AB  - Probanda affected with autosomal dominant polycystic kidney disease (ADPKD) had a
      molecular genetic analysis which indicated the type I. Of the three pregnancies
      in the probanda, first two had mutant gene carrier fetuses and these pregnancies
      were terminated. The fetus of the third pregnancy had no mutant gene and this
      pregnancy ended in the birth of a healthy boy. The principles of genetic
      counselling and antenatal care are summarised in ADPKD type I.

PMID- 9254375
TI  - [The diagnostic value of IgG galactosylation in rheumatoid arthritis].
AB  - Glycosylation is the main posttranslational modification of protein molecules.
      Human immunoglobulin G (IgG) is unique among serum glycoproteins because it is
      associated with at least 30 different biantennary oligosaccharide moieties.
      Elevated ratio of circulating IgG molecules lacking galactose from the
      oligosaccharides on the CH2 domain correlates with severity of the disease in a
      number of different autoimmune illnesses. Moreover, it may be helpful in
      differential diagnosis of rheumatoid arthritis (RA). By that we may try to
      predict outcome of RA. Its seems that agalactosyl IgG is distinctively connected
      with rheumatoid arthritis and may be involved in its immunopathogenesis.

PMID- 9254376
TI  - [Aladar Fay, M.D. (1864-1944)].

PMID- 9254377
TI  - [P. E. Roux, French pioneer of microbiology, honorary doctor of the Budapest
      University of Sciences].

PMID- 9254378
TI  - [Incidence of depression in Hungarian homes for the aged].

PMID- 9254379
TI  - [To the history of radiation therapy planning for cancer patients].

PMID- 9254380
TI  - Does bed sharing affect the risk of SIDS? American Academy of Pediatrics. Task
      Force on Infant Positioning and SIDS.
AB  - The American Academy of Pediatrics endorses and accepts as its policy the
      position on bed sharing as articulated below by a panel of experts convened by
      the National Institute of Child Health and Human Development (NICHD). The Panel
      attended a conference sponsored by the NICHD entitled "Infant Sleep Environment
      and SIDS Risk" in Bethesda, MD, on January 9-10, 1997. After hearing
      presentations from a variety of experts from the United States and several other
      countries, the Panel prepared the following statement regarding the relationship
      of bed sharing and SIDS.

PMID- 9254381
TI  - Screening examination of premature infants for retinopathy of prematurity. A
      joint statement of the American Academy of Pediatrics, the American Association
      for Pediatric Ophthalmology and Strabismus, and the American Academy of
      Ophthalmology.

PMID- 9254382
TI  - Alternative therapy for colds.

PMID- 9254383
TI  - RespiGam/PREVENT study questioned.

PMID- 9254384
TI  - Skeptic questions results.

PMID- 9254385
TI  - Tolerable life.

PMID- 9254386
TI  - Idiopathic status epilepticus.

PMID- 9254387
TI  - In search of therapeutic nursing: subacute care.
AB  - A form of 'intermediate' care exists in the USA which parallels the work of nurse
      led units in the UK. This article describes subacute care, the term used for in
      patient facilities for post-operative care and rehabilitation, and looks at its
      application in the USA. The work of such units is detailed and compared with
      similar units in the UK.

PMID- 9254388
TI  - Sibling rivalry? Two physician brothers and the accident that changed their view
      of the profession.

PMID- 9254389
TI  - Reporting of adverse drug reactions.

PMID- 9254390
TI  - Is routine screening for colorectal cancer justifiable? This gastroenterologist
      says NO!
AB  - In this era of resource limitations, use of healthcare dollars should be directed
      to diagnostic and therapeutic programs that can be supported by scientifically
      valid information. Screening for colorectal cancer has to overcome two
      limitations before its routine use can be justified. First, the disease is
      largely a problem in elderly patients, who are likely to have comorbid
      conditions. Second, any cancer screening identifies mainly slower-growing lesions
      (i.e., length-time bias), which may be less of a mortal threat in older patients.
      Data available in 1997 cannot justify implementation of colorectal cancer
      screening as a public health policy. My advice to individual patients is not to
      have it done, and we have not instituted the practice at the public hospital
      where I work. I myself have declined it for each of the past 5 years when my
      personal physician has offered it to me.

PMID- 9254391
TI  - Pityriasis.

PMID- 9254392
TI  - Vision: from photon to perception.

PMID- 9254394
TI  - [Epidemiology of viral hepatitis].

PMID- 9254393
TI  - Chronic social stress, social status, and susceptibility to upper respiratory
      infections in nonhuman primates.
AB  - OBJECTIVE: The objective of the study was to assess the roles of social stress
      and social status in susceptibility to upper respiratory infection. METHOD: Sixty
      male cynomolgus monkeys were randomly assigned to stable or unstable social
      conditions for 15 months. Two markers of social status, social rank and percent
      of behaviors that were submissive, were assessed at independent observation
      periods. Endocrine, immune, and behavioral responses were each assessed (at 3
      month intervals) during the 9th through 14th months of the study. At the
      beginning of the 15th month, all animals were exposed to a virus (adenovirus)
      that causes a common-cold-like illness. The primary outcome was whether or not an
      animal developed an infection (shed virus) after viral exposure. RESULTS:
      Although the social instability manipulation was associated with increased
      agonistic behavior as indicated by minor injuries and elevated norepinephrine
      responses to social reorganizations, the manipulation did not influence the
      probability of being infected by the virus. However, low social status (as
      assessed by either marker) was associated with a substantially greater
      probability of being infected. It was also associated with less body weight,
      greater elevated cortisol responses to social reorganizations, and less
      aggressive behavior. However, none of these characteristics could account for the
      relation between social status and infection. CONCLUSIONS: Social stress was not
      associated with susceptibility to infection. However, animals with lower social
      status were at higher risk than high social status animals.

PMID- 9254395
TI  - [Transmission routes of hepatitis C virus in carrier patients and study of family
      contacts].
AB  - A study was made of the routes of transmission of HCV in 106 carrier patients and
      the prevalence of antibodies to HCV antigen (HCV Ab) in 132 family contacts
      (mothers, sexual partners and children of carrier women) attended at a Primary
      Care Center in Madrid. The following data were obtained through a personal
      interview: age, gender and possible routes of contagion. Also, ALT and serologic
      status to HBV. Household contacts were interviewed and HCV Ab status obtained.
      Only in 21 patients (19.8%) was no risk factor found ("sporadic cases"). Eighty
      one individuals (76.4%) and 13 (12.3%) had percutaneous transmission and sexual
      transmission risk factors, respectively. Out of 18 studied mothers, two (11.1%)
      had HCV Ab. The prevalence of HCV Ab in household contacts was 8.35%. These
      results suggest that the proportion of sporadic cases decreases significantly
      when a thorough investigation is carried out in carrier patients. The
      percutaneous route is responsible for most of HCV infections. The prevalence of
      HCV Ab among household contacts appears to be higher than among general
      population.

PMID- 9254396
TI  - [Impact of AIDS on admissions and mortality in an Internal Medicine Department
      (1990-1995)].
AB  - OBJECTIVE: To know and analyze the main causes of death in an Internal Medicine
      Department (MI), as well as the impact of AIDS on admissions and mortality rate
      in such a Department. MATERIALS AND METHODS: A total of 275 patients out of the
      35,521 attended patients from 1990 to 1995 had positive serology to HIV (HIV+). A
      total of 1,793 deaths were recorded, 42 of which were attributed to AIDS.
      Clinical and epidemiologic parameters were studied; also, management parameters
      associated with death were investigated (particularly, those caused by this
      disease). RESULTS: The overall mortality rate was 5.04%, where as the mortality
      rate among HIV+ in patients was 15.27%; the primary causes of death were
      cardiovascular, tumoral, and respiratory disease by decreasing frequency. AIDS
      was the first cause of death in patients aged less than 35 years. As for AIDS,
      the number of admissions on account of this disease had a progressive increase
      along the study period; the mean age of dead patients (31.6 years) tended to
      increase in the last few years and to be significantly higher among men (6
      years); the mean of hospital stay among HIV+ patients (14.16 days) tended to
      decrease in the last few years. CONCLUSIONS: AIDS has had a progressive increase
      and has become the primary cause of hospital death in IM, in patients aged less
      than 35 years. As the experience with this disease increases, the mean stay of
      HIV+ patients decreases, although it tends to increase in patients who ultimately
      die, possibly because of the social changes in the last few years, as disease,
      and particularly death, is intended to become separated from family home.

PMID- 9254397
TI  - [High titers of rheumatoid factor: clinical significance].
AB  - Rheumatoid factor (RF) is one of the most characteristic laboratory parameters in
      rheumatoid arthritis (RA), and its specificity for this disease increases when
      the titer is high. We investigated the diagnoses associated with high titers of
      RF and whether they are associated with a poor prognosis of RA. PATIENTS AND
      METHODS: Patients with RF titers higher than 300 IU/ml were studied
      (nephelometry) during a three-year period in a general hospital. Patients with RA
      were compared with other group of patients with RA and RF lower than 300 IU/ml
      regarding functional capacity, presence of nodules, HLA-DR4 and radiologic
      status, in a retrospective cohort study. RESULTS: RF was quantitated in 2,181
      patients and was higher than 300 IU/ml in 79 cases; 63 among patients in this
      group (80%) had RA, and the remaining patients inflammatory diseases of the
      connective tissue (four patients), palindromic rheumatism (two), liver disease
      (two), infection (one) and neoplasm (one). In two cases the diagnosis was
      arthrosis and in one case arthralgia of unknown origin. RA with RF higher than
      300 IU/ml had a higher frequency of rheumatoid nodules than RA with RF lower than
      300 IU/ml (p = 0.01; RR: 2.26; 95% CI: 1.18-4.35). The index of functional
      capacity and rate of HLA-DR4 and erosions was similar in both RA groups.
      CONCLUSIONS: In a patient with a high RF titer, RA should be first ruled out,
      followed by other inflammatory diseases, collagenosis and liver diseases. The
      likelihood of finding a healthy patient with arthrosis or soft tissue rheumatism
      was very low. In RA, rheumatoid nodules were significantly associated with RF
      with titers higher than 300 IU/ml.

PMID- 9254398
TI  - [Efficacy of acetazolamide treatment of patients with hypercapnia and
      superimposed metabolic alkalosis].
AB  - BACKGROUND: Metabolic alkalosis usually complicates the evolution of patients
      with hypercapnia under diuretic or steroid therapy. The objective of this study
      was to analyze the efficiency of therapy with acetazolamide, a reversible
      carbonic anhydrase inhibitor, in this condition. PATIENTS AND METHODS:
      Prospective study conducted at our hospital from June 1994 to March 1996, with 45
      patients who had chronic respiratory acidosis and metabolic alkalosis. After a
      previous stabilization of the patient and eventually the discontinuation of
      diuretic or corticosteroid drugs fro 24-48 hours, 500 or 750 mg of acetazolamide
      were administered daily for 48 hours. Later, variations both in arterial
      gasometry and venous electrolytes were analyzed by comparing two means of paired
      data. RESULTS: After therapy with acetazolamide a clinical improvement was
      observed in patients, a decrease in PaCO2, pH and CO3H (p < 0.001) and an
      increase in PaO2 (p < 0.001). Hypochloremia (82.2%) and hypopotassemia (33.3%)
      were the most common electrolytic abnormalities before therapy. Both
      abnormalities improved significantly after the administration of acetazolamide.
      In five patients (11.1%) acetazolamide was discontinued when metabolic acidosis
      appeared, which only in three cases was associated with acidemia. No secondary
      effects were observed. CONCLUSIONS: Acetazolamide is an efficient alternative for
      treatment of patients with respiratory acidosis and metabolic alkalosis,
      particularly when other more common measures in this condition (discontinuation
      of diuretics and/or volemic replacement) have failed or are contraindicated. On
      the other hand, the emergence of relevant secondary effects is unlikely.

PMID- 9254400
TI  - [Polymicrobial endocarditis: a clinical and evolutive study of 12 cases diagnosed
      during a 10-year period].
AB  - Polymicrobial endocarditis (PE) is uncommon, whether in series of cases of
      polymicrobial bacteriemia or of endocarditis. Among the 201 cases of infective
      endocarditis seen between 1986 and 1995 by an infectious diseases service, 12
      patients had PE (6%). Nine were males, mean age was 28 years and ten were active
      intravenous drug users. All of them were HIV (+) and 50% had AIDS. Eleven
      subjects had infection of the tricuspid valve and 58% developed septic pulmonary
      emboli. The most common organism encountered was Staphylococcus aureus in 8
      patients followed by Streptococcus viridans and S. pneumoniae in three. The most
      common combinations of organisms were S. aureus and S. pneumoniae in 3 cases and
      S. aureus and Pseudomonas aeruginosa in two. Two patients died, one with
      Xantomona maltophilia and another with Candida albicans. The symptoms of PE were
      usually indistinguishable from endocarditis caused by a single organism and the
      prognosis depended on the species rather than the number of organisms isolated.

PMID- 9254399
TI  - [Antibiotic treatment of acute gastroenteritis].
AB  - The empiric antibiotic therapy for acute gastroenteritis (AGE) is indicated only
      in patients with underlying diseases or risk for bacteremia. The clinical
      characteristics, clinical efficiency of antibiotic therapy with pivmecillinam (52
      patients) or ciprofloxacin (75 patients) and its effects on the fecal carrier
      state of Salmonella spp. were studied in 127 adult patients with AGE and
      antibiotic therapy indication. The initial stool culture was positive in 90
      patients (71%). The microorganism recovered most frequently was Salmonella spp.,
      with a bacteremia rate in these patients of 5%. The susceptibility of Salmonella
      spp. to ciprofloxacin and mecillinam was 100% and 90%, respectively. Therapy with
      ciprofloxacin or pivmecillinam showed a similar efficiency. Fecal excretion
      lasted no longer than five weeks and no chronic carriers were observed.

PMID- 9254401
TI  - [Hepatitis B virus infection in the absence of serological markers or with
      atypical serological patterns].

PMID- 9254402
TI  - [Malignant hypertension].

PMID- 9254403
TI  - [Genetic diversity of hepatitis C virus. Genotypes].

PMID- 9254404
TI  - [A 17-year-old woman with hemoptysic expectoration and interstitial lung
      disease].

PMID- 9254405
TI  - [Progressive exertional dyspnea and characteristic images in thoracic
      radiography].

PMID- 9254407
TI  - [Comparing survival curves].

PMID- 9254406
TI  - [Upper dysphagia with 10-year course].

PMID- 9254408
TI  - [Bronchocentric granulomatosis with unusual presentation].

PMID- 9254409
TI  - [Nodal nocardiosis in 2 patients with HIV infection treated with cotrimoxazole].

PMID- 9254410
TI  - [Brown-Sequard syndrome secondary to dissecting aortic aneurysm].

PMID- 9254411
TI  - The purpose of glycolysis.

PMID- 9254412
TI  - Sickle cell anemia research and a recombinant DNA technique.

PMID- 9254413
TI  - Synergistic effect of environmental estrogens: report withdrawn.

PMID- 9254414
TI  - Showdown over clean air science.

PMID- 9254415
TI  - NIH leads research gains as Congress picks up pace.

PMID- 9254416
TI  - Chimp retirement plan proposed.

PMID- 9254417
TI  - European Parliament backs new biopatent guidelines.

PMID- 9254418
TI  - Academy seeks government help to fight openness law.

PMID- 9254419
TI  - Biologists cut reductionist approach down to size.

PMID- 9254420
TI  - Gram-positive bacterium sequenced.

PMID- 9254421
TI  - How jet-lag hormone does double duty in the brain.

PMID- 9254422
TI  - Proinsulin C-peptide--biological activity?

PMID- 9254423
TI  - PtdIns(3,4,5)P3 gets its message across.

PMID- 9254424
TI  - Fighting dengue in Cuba.

PMID- 9254425
TI  - Transgenic lambs from cloning lab.

PMID- 9254426
TI  - Ban has mixed impact on Texas, California grad schools.

PMID- 9254427
TI  - Archaeologists rediscover cannibals.

PMID- 9254428
TI  - Feeling a protein's motion.

PMID- 9254429
TI  - A developmental biology summit in the high country.

PMID- 9254430
TI  - New insights into how babies learn language.

PMID- 9254431
TI  - Of topo and Maxwell's dream.

PMID- 9254432
TI  - For self-starting scientists a "model" career awaits.

PMID- 9254434
TI  - [Mother-infant rooming-in and exclusive breast feeding].
AB  - OBJECTIVE: To determine the influence of joined mother-child hospital lodging
      (JL) on the frequency of exclusive human lactation (EHL) from birth to four
      months of age. MATERIAL AND METHODS: Non-randomized cohort study performed at the
      lactation clinic of the "Luis Castelazo Ayala" Hospital of the Mexican Social
      Security Institute from January 1993 to October 1994 which included 178 healthy
      mother-child pairs (MCP) with term pregnancy. The jointly lodged group (JL)
      consisted of 90 MCP in which mothers received assessment for lactation; 88 MCP
      were lodged separately and no assessment was provided. Results were statistically
      analyzed to determine frequency and variable associations. RESULTS: Feeding was
      recorded as either EHL, powdered milk or both. Groups with or without JL were
      stratified by form of birth, either labor or Cesarean section. With the Mantel
      Haenszel X2 and logarithmic range, differences were significant with p < 0.05.
      During the study, global lactation was similar among groups. In the first month,
      EHL was higher in the JL group, 61 vs 42% independently of the form of birth (p <
      0.05). The only variable which influenced EHL was JL. CONCLUSIONS: Mother-child
      JL favours EHL during the first month post-partum.

PMID- 9254433
TI  - [The federal health expenditure on the uninsured population: Mexico 1980-1995].
AB  - In the last fifteen years Mexico suffered several economic crisis which have
      negatively affected public expenditure in social welfare and, as a consequence,
      public expenditure in health. This paper discusses the relationship between the
      adjustment policies adopted to confront these crisis and public expenditure in
      health care for the non-insured population, as well as the regional distribution
      of this expenditure. In part one, the evolution of general public expenditure,
      public expenditure in social welfare, and public expenditure in health between
      1980 and 1995 is described. In part two, the distribution of public health
      expenditure for the non-insured population among the five regions in which the
      country was divided by the National Health Survey II is discussed. The main
      conclusion of this paper is that, between 1980 and 1995, the public expenditure
      gaps that have existed for a long time in Mexico among regions remained
      unchanged. These gaps basically affect the southern states of the country, are
      not related to health needs, and may deepen in view of the new relative cuts in
      public expenditure in social welfare announced by the new administration.

PMID- 9254435
TI  - [The economic costs in the production of health services: from the cost of inputs
      to the cost of case management].
AB  - OBJECTIVE: To generate information on costs of health services. MATERIAL AND
      METHODS: Using Kessner's criteria the tracer conditions selected were:
      hypertension, diabetes, diarrhea and pneumonia. Case-management definitions were
      established and then, -using the case-management costing method-the production
      functions, inputs and unit costs necessary to meet the demand for medical care
      per condition. Data were processed in a spreadsheet software package to estimate
      in-patient and out-patient case-management costs. RESULTS: Findings from this
      study show that using in-patient and out-patient case-management costing it is
      possible to identify the relative weight of the different production functions
      and inputs. Using the relative frequencies, both production functions and inputs
      were classified in high, medium and low impact on the total case-management cost.
      CONCLUSIONS: This information suggests that planning, organization and resource
      allocation should be guided by in-patient and out-patient service demands for
      each tracer conditions. In addition we suggests direct action to stimulate the
      obtention of economic earnings from resources utilization in the most efficient
      way.

PMID- 9254437
TI  - [Dental caries in schoolchildren of the Federal District].
AB  - OBJECTIVE: To estimate the prevalence and severity of dental caries and the
      dental treatment necessities of school children in Mexico City. The studied
      population was surveyed for dental caries in 1988 to obtain data necessary for
      the National Program of Salt Fluoridation in Mexico. MATERIAL AND METHODS: The
      population was selected with a sample frame based on a list of Kindergartens and
      primary schools registered at the Ministry of Public Education in 1988. The oral
      cavity examination was based on diagnostic criteria marked by the World Health
      Organization. RESULTS: A total of 4475 scholars of 5 to 12 years of age were
      included in the study. Dental caries prevalence in the population reached 90.5%.
      The index of treatment necessities was high (79.6%). The mean of caries index in
      scholars of 12 years of age was DMFT = 4.42 (SD = 3.2) and DMFS = 6.53 (SD =
      4.8). CONCLUSIONS: Results emphasize the pertinence of a widely reaching
      preventive program of such as salt fluoridation. Additionally, strategies to
      improve access of the school children population to dental services must be
      elaborated.

PMID- 9254436
TI  - [Tobacco consumption in the population insured by Mexican Institute of Social
      Security].
AB  - OBJECTIVE: To determine the prevalence of tobacco consumption among the active
      insured population of the Mexican Social Security Institute. MATERIAL AND
      METHODS: A cross-sectional study in which the active insured population from the
      36 political delegations was interviewed by means of a structured and self
      applicable questionnaire on tobacco consumption, age of initiation, amount of
      cigarettes consumed and suspension. RESULTS: The sample consisted of 45 117
      subjects, of which approximately half were men and half women. Smoking prevalence
      in men was 40% and in women, 17.6%. Prevalence was highest in the north of the
      country. There is an effect of age on tobacco consumption and more than half
      started smoking during adolescence. CONCLUSIONS: Smoking prevalence was found to
      be high, however, the average number of cigarettes is low. Suspension index is
      low. Public health measures are necessary to diminish this addiction.

PMID- 9254438
TI  - [Teenage pregnancy as a public problem: a critical view].
AB  - The present work is a review of the most commonly used arguments to define
      pregnancy during adolescence as a public problem: its supposed increase,
      contribution to accelerated population growth, adverse effects on maternal and
      child health and contribution to the persistence of poverty. Some elements are
      proposed for an alternative explanation with the intention of defining with more
      rigour and pertinence the real problems related to pregnancy during adolescence,
      thus allowing an improvement in the design of policies and programs to confront
      it.

PMID- 9254439
TI  - [Transitions: lives, institutions, ideas].

PMID- 9254440
TI  - [The inaugural speech for the School of Public Health. 1922].

PMID- 9254441
TI  - [The uses and effects of the Calmette-Guerin Mycobacterium bovis bacillus (BCG
      Vaccination)].

PMID- 9254442
TI  - [The relevant aspects on the hospital discharge statistics of the National Health
      System].

PMID- 9254443
TI  - [Update topic: the uses and effects of the Calmette-Guerin Mycobacterium bovis
      bacillus (BCG vaccine)].

PMID- 9254445
TI  - 1997 State of the Art. Proceedings of the XVIth Congress of the International
      Society on Thrombosis and Haemostasis.

PMID- 9254444
TI  - [Seasonal variation in mortality in the city of Valencia, Spain].
AB  - OBJECTIVE: To study the seasonal variation in mortality for all causes, grouped
      according to age and sex, within the city of Valencia during the period 1976-1990
      and its relationship with air temperature. MATERIAL AND METHODS: This is an
      ecological study using monthly global mortality and mean atmospheric temperature
      statistics for the city of Valencia, Spain between 1976 and 1990. The principal
      variable has turned out to be mortality for all causes. Mortality rates have been
      determined for specific age groups (0-4, 35-49, 50-64, 65-74 and > or = 75), as
      well as for both genders, within the city of Valencia for each of the 180-month
      period of investigation. Average monthly mortality data has been obtained and the
      percentage variation has been calculated. Graphical analysis has been used to
      examine the seasonal variation in mortality and in order to discern the nature of
      any relationship between atmospheric temperature and mortality. The regression
      line has been adjusted using the Loess method (smoothed regression motive,
      locally pondered). The association between mean temperature and mortality has
      calculated by means of multiple regression analysis controlling for trend,
      seasonality and period effect. RESULTS: A clear seasonal pattern emerges with
      mortality peaking during the Winter months and dipping during the Summer and
      early Autumn. The increase in mortality seen during the month of January came to
      27.7% of the total mortality for females and 19.5% of the total mortality for
      males. By age groups, this increase was greater in the 75-plus age group.
      Graphically, the relationship between temperature and mortality has a V-shape
      appearance, with a lower mortality level when the mean daily temperature for the
      month in question is approximately 23 degrees Celsius. Based on this
      relationship, two complementary.

PMID- 9254446
TI  - Proceedings of the 6th International Sendai Symposium on Biliary Atresia. Japan,
      May 20-21, 1996.

PMID- 9254447
TI  - [Biological age: the forensic medical aspects].
AB  - All methods for assessing the age of man are based on the use of parameters of
      biological aging. Discrepancies between the biological and actual age make
      impossible the precise determination of actual age. The extent of expert error
      depends on the type of aging, the greatest error being observed in hyperergic and
      the least in asynchronous aging. Expert evaluation of age can be made more
      precise if the complex of diagnostic parameters be extended; these parameters
      should be selected strictly in accordance with the specific requirements to
      assessment of age. Addition of the parameters of aging of the endocrine glands
      and other organs and tissues appears to hold good promise.

PMID- 9254448
TI  - [The status and goals of research in forensic chemistry in the Russian
      Federation].

PMID- 9254449
TI  - [An analysis of the errors in determining the time of death by cadaveric changes
      during the performance of the initial inquiry activities].
AB  - Analysis of 265 forensic medical expert conclusions on murdered subjects' corpses
      permitted us to quantitatively and qualitatively evaluate the errors made by
      forensic medics examining the corpse at the site where it was found. In 23.4% of
      cases these errors were due to improper methodology of thanatometric
      investigations and were made by forensic medics of different length of service
      and qualification. Approaches to improving the diagnosis of time of death during
      the initial investigation are outlined.

PMID- 9254450
TI  - [The forensic medical service of the Russian Federation (its status, problems and
      developmental outlook)].

PMID- 9254451
TI  - [The use of a method of sequential mathematical analysis for the differential
      diagnosis of trauma from a fall from a height and of trauma due to the collision
      of a moving automobile with a pedestrian by the chest injuries].
AB  - Fifty cadavers of subjects dead after falling from height and 50 cadavers of
      subjects dead as a result of collisions between moving cars and pedestrians were
      examined. Under study were injuries to soft tissues of the chest, thoracic bones
      and viscera, and combinations thereof. Mathematical probability successive
      analysis after Gubler (1978) helped distinguish 64 highly informative injuries
      signs which permit determining the type of injury. Diagnostic coefficients and
      informative value of these signs are presented in the differential diagnostic
      table.

PMID- 9254452
TI  - [A comparative analysis of the chest injuries in different types of traumatic
      exposure].
AB  - A total of 200 death cases from various injuries are analyzed using the files of
      the Kaliningrad Bureau of Forensic Medical Expert Evaluation over 1991-1992.
      Chest injuries were found to occur most often in men aged 31 to 40. The
      predominant lesions are abrasions, hemorrhages in soft tissues, rib fractures,
      and lung injuries.

PMID- 9254453
TI  - [The complex forensic medical study of the bony remains from a burial long ago].
AB  - A complex of methods of forensic medical expert evaluation of bone rudiments,
      including identification osteological, spectral, histological, and biological
      studies, files of historical archives, archaeological and soil science data,
      helped tentatively determine the time of burial and assess the individual
      features of subjects buried at the territory of an ancient orthodox monastery.

PMID- 9254454
TI  - [The infliction of harm to health in light of the provisions of the new Criminal
      Code of the Russian Federation].

PMID- 9254455
TI  - [Tuberculous sepsis in expert practice].

PMID- 9254456
TI  - [The death of a newborn infant from ethanol poisoning].

PMID- 9254457
TI  - [The regulations for the forensic medical expertise of the severity of harm to
      health. Appendix 2 to the order of the Ministry of Public Health of the Russian
      Federation of 10 December 1996 No. 407].

PMID- 9254458
TI  - [S. F. Khotovitskii--one of the founders of forensic medicine in Russia (on the
      200th anniversary of his birth)].

PMID- 9254459
TI  - [The All-Russian Society of Forensic Medical Personnel in the period between
      congresses (1992-1996)].

PMID- 9254460
TI  - [The status of research in forensic medicine and the introduction of the results
      of research work into expert practice].

PMID- 9254461
TI  - Latex agglutination test for visceral leishmaniasis.

PMID- 9254462
TI  - Control of tubercular haemoptysis by bronchial artery embolization.
AB  - Thirty-seven patients presenting with massive or recurrent haemoptysis secondary
      to tuberculous aetiology were subjected to bronchial artery angiography. Of
      these, failure, to catheterize the bleeding vessel occurred in two patients while
      embolization was withheld in two patients due to the presence of anterior spinal
      artery arising from a common intercosto-bronchial trunk. Immediate arrest of
      bleeding was performed in the remaining 33 patients by selective embolization of
      the abnormal bronchial arteries with a resorbable material (Gelfoam). Regular
      follow up for a duration of 6 months after the procedure revealed relapse of
      haemoptysis in four patients; three were treated by re-embolization of the
      abnormal bleeding vessels while one patient died due to aspiration immediately on
      admission. No recurrence of bleeding was seen in the remaining 29 patients. It is
      concluded that bronchial artery embolization is an effective treatment for
      immediate control of life-threatening haemoptysis.

PMID- 9254463
TI  - Special issue dedicated to Professor Georg Rutishauser on the occasion of his
      70th birthday.

PMID- 9254464
TI  - [Means for improving therapeutic care under the conditions of local war and the
      problems in training medical personnel].

PMID- 9254466
TI  - [The sequelae and problems of the Chernobyl catastrophe].

PMID- 9254465
TI  - [Emergency care for infectious disease patients].
AB  - Urgent critical condition during acute course of infectious diseases can be
      developed in early terms and suddenly with fast irreversible changes in vital
      organs and systems. In connection with generality of pathogenesis of many groups
      of infectious diseases the critical conditions characterized by stereotyped
      clinical syndromes. They include infective toxic shock, infective toxic
      encephalopathy and cerebral hypertension, acute dehydration, acute respiratory,
      cardiac, hepatic, adrenal and renal insufficiency. Urgent therapeutic measures
      can be standardized with reference to that or other syndromes of critical
      conditions. In their number--prescription of glucocorticosteroids, diuretics,
      neuroleptics, antipyretic preparations, solutions of various applicability.
      Application of antimicrobic preparations and specific antitoxic serums,
      antimalarial preparations requires care in connection with possible development
      of complications of toxic or allergic character.

PMID- 9254468
TI  - [The basic trends in the reform of military medical education].
AB  - Specific character of military medical training in the Armed Forces of Russian
      Federation is defined by lack of multilevel structure of pre-graduated
      preparation. At a pre-graduated stage during 7 years only preparation of the
      specialists is carried out--in Military Medical Academy (St.-Petersburg) and on
      the military medical faculties (MMF) at medical state universities. According to
      the concept of development of military medical education in the Armed Forces of
      RF (1996) is planned: to apply widely psychologic selection and psychophysiologic
      "support" of cadets and students at all stages of preparation; during transition
      period, till 2003 year, to carry out primary specialization at the medical high
      schools, at military post-graduated courses and at officer's courses of MMF: to
      stop after 2003 primary specialization of graduated from military medical high
      schools at post-graduated course. Finally medical discipline graduated from high
      schools will choose after 3-years service in the units. The article consider
      questions about preparation of younger medical specialists (sanitary instructors
      and medical assistants), and also military medical preparation of all servicemen
      on rendering first care to injured and ill.

PMID- 9254467
TI  - [The nature of the changes in the immunity of the women who worked in the cleanup
      of the sequelae of the accident at the Chernobyl Atomic Electric Power Station
      and were evacuated from the radioactively contaminated area].
AB  - During examination of 37 women taking part in elimination of consequences of
      Chernobyl's disaster was revealed, that complex of disaster factors action
      resulted the formation of disbalance in the system of immunocompetence cells and
      caused the oppression of functional activity of neutrophils. In 110 women living
      on the radioactive contaminated zone (5-40 Ci/km) the phenomena of the secondary
      immunodeficiency in the form of defeat as cellular as humoral factors of immunity
      and nonspecific resistance system was diagnosed.

PMID- 9254469
TI  - [A comparative evaluation of the treatment procedure for the victims of the
      earthquakes on Iturup and Sakhalin].

PMID- 9254470
TI  - [Acute hemorrhage: its classification and the determination of its size and
      severity (1)].

PMID- 9254471
TI  - [Infusion-transfusion therapy at stages of medical evacuation].

PMID- 9254472
TI  - [The structure of battle trauma to the brain and the organization of the delivery
      of neurological care at stages in the medical evacuation in armed conflicts].

PMID- 9254473
TI  - [Successful x-ray endovascular prosthesis in abdominal aortic aneurysm].

PMID- 9254474
TI  - [The structure of the irreversible losses in modern armed conflicts].

PMID- 9254475
TI  - [The use of Sandostatin in the combined treatment of acute destructive
      pancreatitis].

PMID- 9254476
TI  - [Tragic pages in the life of brigade physician P. I. Timofeevskii].

PMID- 9254477
TI  - [Experience in improving outpatient polyclinic care].

PMID- 9254478
TI  - [The organizational problems in the postgraduate and additional professional
      training of military physicians].
AB  - In the article materials of social research on problems of postgraduate and
      additional vocational training are analyzed. Original analytical results are
      received, which characterize real periodicity and volume of increase of
      qualification of the military doctors, permit deeper to estimate necessity of
      perfection of military-medical education, put particular questions, concerning
      improvements of quality of professional training. Research lead to the conclusion
      about necessity of further scientific search in this direction.

PMID- 9254479
TI  - [The rehabilitation of the wounded with combat injuries to the extremities].
AB  - In the article necessity of organization of system of rehabilitation of the
      wounds in the limbs is emphasized, its main rules, components, problems and
      methods are opened. Due to early specialized surgical care in combination to
      modern conservative grant terms of stationary treatment are much reduced, in 2
      times quantity of good remote results is increased, in 3 times number of bad
      outcomes, in 1.5 time--number of retired, on 15.2%--physical inability are
      reduced. Ways of further perfection of system of complex rehabilitation treatment
      are planned.

PMID- 9254480
TI  - [The current procedure for the surgical treatment of combat gunshot eye
      injuries].

PMID- 9254482
TI  - [Threshold tables for the study of color vision in military medical expertise].

PMID- 9254481
TI  - [The diagnosis of lesions of the venous collectors of the brain].
AB  - Comparative data of transcranial ultrasonic dopplerography (170 patients) and
      radionuclide antroscintigraphy (124), received during diagnostics of defeats of
      venous collectors of brain are analyzed. Five variants of defeats of venous
      collectors (cross, sigmoid, internal of jugular vein), but also unpaired sine
      (direct, confluent) are described. Received results permit to reveal
      interrelation of infringements of venous outflow and increase of intracranial
      pressure.

PMID- 9254483
TI  - [Variants of progressive dementias in middle-aged and elderly persons].

PMID- 9254484
TI  - [The methodological aspects in determining standards in the demand for surgical
      beds].

PMID- 9254485
TI  - [The use of mathematical modelling methods in clinical practice].

PMID- 9254486
TI  - [The mental state of servicemen released from captivity].
AB  - The clinical and medico-psychological research of the servicemen, long time
      staying by hostages in captivity is lead. Boundary mental frustration, in
      particular neurotic reactions and the conditions, asthenodepressive syndrome,
      posttraumatic stress frustrations, are revealed in 45.8% surveyed. The most
      psychotraumatic is initial period of adaptation to conditions of captivity. The
      necessity to carry out the measures of medico-psychological rehabilitation and
      treatment of the servicemen, released from captivity, should be taken into
      account during planning of medical maintenance of the troops in local wars and
      armed conflicts.

PMID- 9254487
TI  - [The effect of extreme ecological factors on the resistance of the healthy human
      being].

PMID- 9254489
TI  - [Relics of the front: Stalingrad-Berlin].

PMID- 9254488
TI  - [Pathology of the circulatory system in officers of the Naval Fleet: an analysis
      of the trends and means for decreasing morbidity].

PMID- 9254490
TI  - [The training of medical workers in a partisan detachment].

PMID- 9254491
TI  - [Outstanding scientist, therapist and teacher (on the centenary of the birth of
      M. S. Vovsi)].

PMID- 9254492
TI  - [The contribution of S. F. Khotovitskii to the creation and development of the
      Voenno-meditsinskii zhurnal].

PMID- 9254493
TI  - [The psychoemotional status and cardiovascular system function of patients with
      ischemic heart disease and hypertension receiving physio- and balneotherapy].

PMID- 9254494
TI  - [Hyperbaric oxygenation in the combined sanatorium rehabilitation of patients
      with corrected heart defects].

PMID- 9254495
TI  - [Intracranial electrostimulation in partial circulatory failure in man].

PMID- 9254496
TI  - [The effect of nitrogen silicide thermal mineral water on stomach function in
      gastroduodenal pathology].
AB  - Patients with ulcer, hyperacid and normal acid gastritis were given nitrogen
      silicate mineral water from Annensk thermal springs. The water was found to
      inhibit acid-pepsin-forming function and to improve gastric motility and
      evacuation. Acceptable fluoride concentration and not a single case of the
      disease aggravation make the above mineral water suitable for rehabilitation of
      patients with ulcer and gastritis.

PMID- 9254497
TI  - [The correction of prostatic hemodynamics in chronic prostatitis].
AB  - Prostatic rheography findings evidence for marked disturbances of venous outflow
      in patients with chronic prostatitis. To correct the hemodynamics, rectal
      magnitotherapy was used in two regimens: with constant frequency of the magnetic
      field (5000 Hz) and fluctuating magnetic field (1-20000 Hz). The comparison of
      the results gave priority to the latter regimen because it provided reduction of
      the treatment duration and normalization of rheographic parameters in 37 (90.2%)
      patients. The authors recommend rectal magnitotherapy for combined treatment of
      chronic prostatitis.

PMID- 9254499
TI  - [The biological activity of the therapeutic sapropel muds of Siberia].

PMID- 9254498
TI  - [The indices of intraerythrocyte metabolism and hemoglobin oxygen affinity in
      volleyball players under intensive physical loads].
AB  - The authors' investigations led them to the conclusion that skilled volleyball
      players' erythrocytes undergo adaptive metabolic rearrangement. There was also
      low hemoglobin affinity to oxygen. A single training load provoked the effect of
      metabolic enhancement as a result of increased red cell concentration of glucose,
      glycosylated hemoglobin and high activity of hexokinase.

PMID- 9254500
TI  - [Vitamin complexes as one of the indices of the biological activity of peloids].

PMID- 9254501
TI  - [The creation of a legal-standards basis for the economic validation of nature
      preserving activities in health resorts].

PMID- 9254502
TI  - [The sanatorium-health resort service under market economy conditions].

PMID- 9254503
TI  - [The participation of antioxidant systems in adaptive body reactions to the
      action of physical factors].

PMID- 9254504
TI  - [An integrated evaluation of the adaptation system and existing risk factors as a
      method for the objective assessment of the efficacy of sanatorium-health resort
      treatment].

PMID- 9254505
TI  - [Methods of nondrug therapy: a view of their systematic development (the
      valeological and social perspectives)].

PMID- 9254506
TI  - [The effect of physical factors on the active transport of sodium ions across
      cell membranes].

PMID- 9254507
TI  - [The 60th anniversary of the Azerbaijan Research Institute of Medical
      Rehabilitation and Natural Therapeutic Factors].

PMID- 9254508
TI  - [Environmental anomalies and their effect on the nature of the exacerbations of
      cardiovascular pathology].

PMID- 9254509
TI  - [Mechanisms of antitumor activity of carotenoids].
AB  - Carotenoids are shown to inhibit the initiation phase of carcinogenesis due to
      their antioxidant activity. But neither antioxidant nor pro-vitamin properties of
      these pigments can explain their antitumor action in many cases. Studying this
      problem another property of carotenoids must be accounted: their ability to
      modify biomembranes reinforcing lipid bilayer and decreasing its fluidity. High
      level of membrane fluidity is characteristic of the tumor cells and they are very
      sensitive to its decrease. Suppressing of membrane fluidity is the mechanism for
      anticancer action of tamoxifen-related compounds, and there are strong reasons to
      suggest the same mechanism for carotenoids.

PMID- 9254510
TI  - [Platelet activating factor--role in regulating the functional activity of the
      mononuclear phagocyte system].
AB  - Data on the synthesis of platelet-activating factor (PAF) and it's natural
      analogues by mononuclear phagocytes, PAF-receptor expression in these cells and
      PAF action on monocytes and macrophages are summarized. Special attention is paid
      to the biochemical events during processes named above. Considered phenomena are
      evaluated as important parts of total organism defence system.

PMID- 9254511
TI  - [A synthetic fragment of insulin with insulin-like biological activity].
AB  - We have used computer modeling of insulin 3-D structure and experimental data
      about action of site point mutation on insulin activity to design functionally
      important domain with signaling activity and synthesized peptide than might be
      sufficient for the binding to insulin receptor. The designed and synthesized
      peptide consist of ten residues and may be obtained in two forms: oxidized and
      reduced (with or without disulfide bond). The synthesized decapeptide peptide
      represents functionally important site for binding to the insulin receptor. Amino
      acid residues at position 1-8 correlate with B-chain of insulin at position (B19
      B26). Residues at position 9.10 correlate with A-chain at position A-10-A21. This
      peptide was tested with cell culture L-929 (glucose uptake) in comparison with
      bioactive commercial peptide (R-G-FF) and insulin. It was shown that synthesized
      peptide exhibit biological activity at molar concentration 0.01-1 mkM. Our
      results successfully demonstrate the synthetic insulin fragment have insulin-like
      biological activity.

PMID- 9254512
TI  - [Effect of a sodium transmembrane gradient on efflux of creatinine from the
      myocardium].
AB  - Heart maintains a gradient for creatine under physiological conditions, so that
      creatine release is relatively small. Calcium depletion, addition of strophanthin
      or decrease of sodium concentration (till 80 mM) provoke release of creatine.
      Elevation of transmembrane sodium gradient by raising of extracellular sodium
      concentration prevented loss of creatine. The effect of elevated concentration of
      sodium ions was blocked by strophanthin but depended on osmolarity, because
      solutions with the same osmolarity that hypersodium media had no protective
      effect on release of creatine. A sarcolemmal mechanism of Na creatine
      cotransports is proposed.

PMID- 9254513
TI  - [Change in histone proteins in rat liver chromatin during exposure of the animal
      to functional stress].
AB  - Pattern of rat liver histones at intensive physical exercises with preliminary
      injection of lysosomotropic drugs was studied by method of electrophoresis in
      PAAG. Elevation of the acetylated forms of histone H4 was revealed. The increased
      proteolysis of lysine-rich histones (H1, H2A, H2B) was shown in swimming rats
      previously stimulated by prodigiosan. The possible role of lysosomal proteinases
      of liver cells in mechanism of chromatine activation is discussed.

PMID- 9254514
TI  - [Comparative study of the action of antineoplastic platinum compounds with
      varying nephrotoxic effects].
AB  - Studying the action of the two antitumour platinum compounds--cisplatin capable
      of exerting a nephrotoxic action and cycloplatam which has no damaging effect on
      the kidney, it was found that 3 h after the administration of cycloplatam the
      content of platinum in the kidney was 2 times lower than in the cfse of
      cisplatin. Due to different dynamics of the excretion of platinum compounds from
      the kidney 5 lays after their addition the content of platinum in the kidney was
      the same in both cases. The content of platinum in the nuclei, mitochondria and
      supernatant with respect to a total content in the kidney cortex was almost equal
      for both compounds. Inhibition of nephrotoxic effect of cisplatin after the
      animals were pretreated with choline chloride or paraaminohippurate is not
      connected with a decrease of platinum in the kidney either 3 h, or 5 days after
      the injection of these preparations. The mechanisms of nephrotoxic action of
      cisplatin and its prevention are discussed.

PMID- 9254516
TI  - [Status of bioenergetic processes in brain of immature rats during the dynamics
      of cranio-cerebral trauma].
AB  - In one month's old rats open cranio-cerebral injury was modelled. During the post
      traumatic period the state of bioenergetic processes in brain tissues was studied
      in dynamics. Disturbance of oxidative phosphorylation in cerebral mitochondria
      and depression of membranes ATPase activity was revealed. This changes were most
      expressed in 1-4 days after the injury. Recovery of the impaired bioenergetic
      processes in post-traumatic period in one month's old rats is slower than in
      adult.

PMID- 9254515
TI  - [Enzyme activity and level of GABA-shunt substrates in rat brain during repeated
      exposure to hypoglycemic doses of insulin].
AB  - The activity of glutamate decarboxylase, GABA-, aspartate-and alanine
      aminotransferases, the content of GABA, glutamate, aspartate and alanine were
      studied in the brain hemispheres and stem of rats that were undergoing the
      hypoglycemic coma as well as those rats had undergone 7-9 comas on the second day
      after the last coma. In hypoglycemia, the brain's content of glutamate, alanine
      and GABA decreased and content of aspartate increased; the activity of enzymes
      investigated did not change. On the second day after 7-9th hypoglycemic coma, the
      decrease of activity of glutamate decarboxylase in hemispheres and the decrease
      of GABA amount in brain stem were detected. This can be an evidence of decrease
      of GABA amount produced and secreted by nerve ends of the pathways leading from
      striata to substantia nigra. The detected changes result from multiple influence
      of hypoglycemia to the brain and may by important in the development of
      posthypoglycemic encephalopathy.

PMID- 9254517
TI  - [Changes in cell membrane lipid composition when exposed to native plasma
      proteins during thermal trauma].
AB  - Changes of phospholipid contents of cellular membranes were investigated on the 1
      and 3 days after thermal trauma. The influence of injection of principle
      antioxidative plasmaproteins-, CP, TF and preparation BITO on phospholipid
      contents was studied. It is shown, that the usage of CP, BITO, TF in less grade,
      helps to reserve easy oxidative fractions and to decrease microviscosity of
      cellular membranes.

PMID- 9254518
TI  - [Coupling of calcium homeostasis and lipid peroxidation in mechanisms of
      bronchial hyperreactivity in patients with bronchial asthma].
AB  - A comparative study of calcium homeostasis, calcium regulating system and lipid
      peroxidation has been done with 16 bronchial asthma patients (BA) at bronchospasm
      of physical effort (BPhE) and with 15 asthma attack patients in remission period.
      The data obtained point to the close pathogenetic link between the changes of
      calcium homeostasis, hormonal calcium regulating system and LPO strengthening the
      appearance of hyperreactivity of bronchial tree and BA.

PMID- 9254519
TI  - [Inactivation of serotonin in patients with hemorrhagic fever with kidney
      syndrome].
AB  - In 150 patients with epidemic hemorrhagic fever hyperserotoninemia,
      thrombocytopenia, increase in the activity of monoamine oxidase, ceruloplasmin
      and serotonin pectic effect were found. However only during mild cases of the
      disease inactivation of serotonin was effective and changes of its concentration
      in plasma were absent.

PMID- 9254520
TI  - [Activators and inhibitors of fibrinolysis in chronic glomerulonephritis and
      amyloidosis].
AB  - Functional activities of plasminogen activators (FPAA) and their inhibitors and
      plasminogen activators's (PA), antigen level were determined in 31 patients with
      chronic glomerulonephritis, 23 patients with amyloidosis and 15 healthy persons.
      High FPAA correlated with favourable prognosis of diseases, elevated PA antigen
      level and diminished alpha 1-antitrypsin, alpha 2-macroglobulin and antiactivator
      activities. There were decreased PA antigen level and increased inhibitor's
      activities in group with zero FPAA. Protein loaded functional probe demonstrated
      the presence of PA reserves in high FPAA patients and "pathological proteolysis"
      in zero FPAA patients. The last phenomenon was likely connected to nonspecific
      proteases differed from PA.

PMID- 9254521
TI  - [Analysis of the connection between the level of protein fractions and
      immunoglobulins in blood serum with irradiation in nuclear power enterprise
      workers].
AB  - 989 workers of atomic industry at the age from 35 to 78 years old subjected to
      the general external gamma radiation and incorporation of plutonium 239 in a wide
      range of doses about 17-40 years ago have been examined for the protein indices
      with the radiation effect bearing in mind nine non-radiation factors. The step-by
      step regression analysis revealed a positive linear link for the total protein
      level, absolute content of alpha-I-globulins with the total dose of external
      gamma radiation. Increasing of serum proteins entropy, correlated with external
      radiation by protein shifts effect, had not coincided with its age increasing.
      The influence of plutonium-239 incorporation on the examined protein parameters
      was not found.

PMID- 9254522
TI  - [Search for expansion of CAG-repeats in DNA sequences expressed in the brain of
      humans with psychiatric and neurological diseases].
AB  - Dynamic mutations due to trinucleotide repeat expansion are a new class of human
      genome mutations. CAG repeat expansion in the coding region of associated genes
      is the molecular genetic basis of the several diseases of nervous system. Eight
      DNA sequences with CAG repeats expressed in human brain were chosen from the
      GenBank database. The search of CAG expansion was carried out for patients with
      schizophrenia (brain and blood) and essential tremor. CAG repeat expansion has
      not been found for the loci. The distribution of allelic sizes is similar in the
      patients and control samples. Locus HS0073 has shown the polymorphism of the
      length for CAG repeat alleles. Statistically reliable excess of the homozygotes
      has been found for schizophrenic patients.

PMID- 9254523
TI  - [Possibility of regulating platelet aggregation ability with the S2-receptor
      blocker, naftidrofuril, in patients with insulin-dependent diabetes mellitus].
AB  - The actions of S2-receptor antagonist naftidrofuril (Duzodril-retard, Byk Gulden,
      FRG) on both basal and thrombin-induced levels of malondialdehyde in platelets as
      well as platelet aggregability in patients with insulin-dependent diabetes
      mellitus with or without angiopathies were studied. Significant decrease in the
      basal level of MDA was observed after treatment and the effect was more profound
      in patients without vascular complications. The treatment with Duzodril-retard at
      daily dose of 200 mg during 40 days was not shown to decrease in platelet
      hyperfunction in response to the inductors: ADP, 1 and 5 microM; adrenaline, 1
      microM; collagen, 4 mu/ml; ristomycin, 0.9 and 1.2 mg/ml; and thrombin 0.5 U/ml).
      The reduction of hyperreactivity of platelets in response to adrenaline in
      patients without angiopathies was found out during treatment with Duzodril
      retard. This could be referred as positive sign for prognosis because of decrease
      in sensitivity of platelets to adrenaline may lead to corresponding decrease in
      reactivity to ADP during long-term usage of naftidrofuril. Platelets of the
      patients were shown to be hypersensitive to ADP at maximal extent. The decrease
      in the sensitivity of platelets to large concentrations of ristomycin was found,
      the fact which may serve as an evident for some normalization of functional
      activity of platelets as well endothelin-platelet interactions in patients
      without vasal complications. Thus, Duzodril-retard has an activity as angio
      protector in most degree at the cases when vasal disturbances are not clinically
      significant yet.

PMID- 9254524
TI  - [Key mechanisms of damage and adaptation in the body under the multi-factoral
      effect of ecotoxicants].
AB  - Toxicants, that are present in chemical productions, influence functioning of
      protective mechanisms of the workers. The examined people have an increased
      content of the average molecular mass oligopeptides, changed ionic molecular
      composition of blood. Antioxidant protection with catalase participation is high.
      The accelerated replacement of membrane components displays an adaptation of
      organism to the chemical stress conditions.

PMID- 9254525
TI  - [Synthesis of beta-maltosides, derivatives of p-nitrophenol, 2-chloro-4
      nitrophenol, and 4-methylumbelliferone, and their use as substrates for
      determining alpha-glucosidase activity].
AB  - Synthesis of beta-maltosides, p-nitrophenyl-beta-D-maltoside and 4
      methylumbelliferyl-beta-D-maltoside, based on interaction of hepta-acetate-beta-D
      maltosyl fluoride with the corresponding trimethylsilyl ethers of p-nitrophenol
      and 4-methylumbelliferone is described. 2-Chloro-4-nitrophenyl-beta-D-maltoside
      was synthesized by interaction of hepta-acetate-alpha-D-maltosyl bromide with 2
      chloro-4-nitrophenol in two phase system using phase transfer catalyst. The
      method of assay of neutral alpha-glucosidase from human kidney and urine using
      synthesized beta-maltosides (p-nitrophenyl-beta-D-maltoside, 2-chloro-4
      nitrophenyl-beta-D-maltoside and 4-methylumbelliferyl-beta-D-maltoside) as
      substrates and beta-glucosidase as an auxiliary enzyme is proposed. The method is
      simple, convenient and 10-fold more sensitive than the commonly used alpha
      glucosidase assay procedure with the corresponding synthetic alpha-glucosides, p
      nitrophenyl-alpha-D-glucoside and 4-methylumbelliferyl-alpha-D-glucoside. A
      modification of the method, with p-nitrophenyl-beta-D-maltoside as substrate, was
      applied to the semi-automatic assay of urinary alpha-glucosidase in 96-well
      microtitre plates.

PMID- 9254526
TI  - [The effect of angiography with disodium fluorescein on the hemorheologic
      parameters of diabetics].
AB  - Chorioretinal angiography with fluorescein is an auxiliary method widely used in
      Ophthalmology which enables us to study the blood/humour and blood/retina/choroid
      interface. The presence of a strange compound in circulation may interfere with
      blood flow homeostasis. With the aim of studying fluorescein influence in blood
      rheology, blood samples were drawn before, immediately after and 30 minutes after
      fluorescein bolus injection; from 10 patients with diabetes mellitus, with or
      without retinopathy, blood fluidity (hematocrit, erythrocyte aggregation and
      whole blood viscosity) and erythrocyte membrane functional properties were
      determined. After fluorescein injection there was erythrocyte hyperaggregation
      (37.7%, p = 0.004), was detected, hemoglobin concentration (p = 0.039) and
      hematocrit (p = 0.013) decrease, and a double time increase of methemoglobin
      concentration (p < 0.001) the erythrocyte membrane hydrophobic region became more
      rigid (p = 0.016). All these abnormalities normalized after 30 minutes. In
      conclusion, fluorescein angiography interferes acutely with the hemorheological
      parameters of patients with diabetes mellitus, with erythrocyte hyperaggregation
      which could interfere with the microcirculation of these patients.

PMID- 9254527
TI  - [Evaluation of the Cell-DYN 35))].
AB  - The Cell-Dyn 3500 is an automated haematology analyzer which quantitatively
      measures and computes haematological quantities including a full "five-part"
      white cell differential. It measures 22 parameters for erythrocytes, white blood
      cells and platelets, also giving the respective histograms. Evaluation of the
      Cell-Dyn 3500 was performed according to the International Committee for
      Standardization in Haematology (ICSH) norms, for a period of 5 weeks. A total of
      1,235 samples were studied by comparison with the Coulter MaxM. The five-part
      white cell differential and the flagging system were estimated and compared with
      the smear examination of 506 samples, by four clinical pathologists trained in
      cytology. Good correlation was obtained within, between batches, and day-to-day,
      for the following parameters: red blood cells (RBC), haemoglobin (HGB), mean cell
      volume (MCV), white blood cells (WBC) and platelets (PLT). The accuracy was
      estimated (RBC, HGB, VGM, WBC and PLT) each day with three different levels of
      titrated controls with good results. The linearity was established for RBC, HGB,
      WBC and PLT. The results obtained were good. Carry-over studies were performed
      according to the Broughton method for the same parameters and the results were
      also good. Stability studies for the automatic parameters including the
      differential white blood cell count showed that these parameters were stable at 4
      degrees C for 48 hours. At room temperature the stability was reduced to 7 hours.
      Agreement was good between the Cell-Dyn 3500 and the Coulter MaxM, for the
      automatic haemocytometric values. The comparative studies between the five-part
      white cell differential of the haematologic analyzer and the manual differential
      showed excellent results for neutrophils and lymphocytes, very good for monocytes
      and eosinophils. For the flag estimation two criteria were established, one based
      on the clinical significance and the other based on the alarm detection described
      in the analyzer manual. The specificity was good for both criteria. In general
      the sensibility was better for the second criteria. The Cell-Dyn 3500 has thus
      shown to be a good haematology analyser which greatly reduces the morphological
      examination of smears.

PMID- 9254529
TI  - [Electrical burns in children. 3 years of case histories].
AB  - The Burn Unit of Dona Estefania Hospital admitted a total of 454 patients from
      January 1992 to January 1995, 24 of these patients suffered from electric shock.
      Of these 24 patients 3 suffered burns in the mouth, 15 in one or both hands and 6
      multiple burns. In 19 patients the burns were up to 1%. A description is made of
      5 cases, male children between the ages of 9 and 13 years, which were deemed
      severe. The incidents occurred outdoors with different voltages and in activities
      considered of ludic or experimental nature: two on the roof of a house, two with
      railway cables and one with an electrical cable in a port zone. The burnt areas
      vary between 4% and 70%, all of them 2nd and 3rd degree, with hospitalization
      lasting from 36 to 116 days. In addition to early and coordinated medical and
      rehabilitative treatment, according to individual needs, a description is also
      made of the cutaneous sequelae (deforming cicatrices, bridles), neurologic and
      psychologic sequelae, with emphasis on a patient who underwent amputation of the
      lower left leg and 4th and 5th ranges of the right foot. It was concluded that
      measures should be taken in education and legislation to prevent these accidents.
      Relevance is given to the need for a multidisciplinary team and specialized
      center for the treatment of these patients.

PMID- 9254528
TI  - [Perinatal morbidity and mortality related to gestational infection. The
      histological identification of chorioamnionitis and its incidence in the
      population studied].
AB  - Infection of the embryo and foetus remains a major public health problem. It has
      been widely accepted as a major cause of spontaneous abortion, premature birth
      and morbidity and mortality of the newborn. Furthermore, many studies stress the
      role of chorioamnionitis in the onset of premature labor. We have found a
      significant incidence of chorioamnionitis in placentas examined in our
      laboratory, but we do not know the real prevalence of intra amniotic infection
      and the magnitude of its consequences. Furthermore, there is no data concerning
      the micro-organisms that can act as pathogens in our patients. The aim of this
      study was to better define the role of infection in pregnancy in our hospital. As
      a first approach we studied all the placentas that were sent to the
      Histopathology Department during 1993, trying to correlate histological findings
      with clinical data. We found that 38% of 280 placentas had histological criteria
      for chorioamnionitis, 33% of which were associated with fetal death. Only 13% of
      these cases had clinical signs of infection. These facts stress the need for a
      sensitive and selective method of identifying organisms that act as pathogens in
      intrauterine infection. It may be possible to prevent some of its complications
      if an earlier diagnosis and identification of the agent are done.

PMID- 9254530
TI  - [Sepsis in the very low-birth-weight newborn infant].
AB  - Sepsis is a common pathology during the neonatal period. Low-birth weight is the
      most important isolated risk factor. With the purpose of determining the
      prevalence of nosocomial infection in newborns of very low birth weight (VLBW),
      finding the microbial flora and the mortality of these patients, the authors
      retrospectively analysed the clinical processes of the hospitalized VLBW in the
      Neonatal Intensive Care Unit (NICU) in S. Joao Hospital in 1993 and 1994. Of the
      1091 newborns admitted to the hospital in these two years, 112 were VLBW (10%).
      Of these, 48 had sepsis-31 (28%) confirmed sepsis and 17 (15%) probable sepsis.
      The agents most commonly found were Staphylococcus epidermidis (44%) and
      Klebsiella pneumoniae (21%). Thirteen patients (27%) died, with infection as the
      cause of death in nine (19%). Our results confirm the importance of nosocomial
      neonatal infection, which should involve the strict observance of the asepsis
      norms and a proper policy of antibiotics.

PMID- 9254531
TI  - [Small for gestational age newborn infants. The effect of standard curves of
      birth weight on the calculation of the prevalence and of the risk factors].
AB  - Sampling decisions, statistical methods and criteria for dating pregnancy all
      influence birth-weight percentiles and the ability to classify a newborn as
      growth retarded or small for date. Consequently the prevalence of small for date,
      the type and the magnitude of risk factors associated with this condition, and
      the evaluation of preventive interventions are dependent on the standards used.
      In this study we established birthweight standards for sex and gestational age
      (36 to 41 weeks) in a sample of 7518 singleton newborns delivered from 1989-92 at
      Famalicao Hospital. Later, these reference percentiles were applied to a sample
      of 2210 to calculate the prevalence of small for date, to evaluate associated
      risk factors, and to compare these estimates with those obtained using Thompson
      or Lubchenco published charts. The prevalence of small for gestational age was
      significantly higher using local standards (9.9 or 10.0%) when compared with
      those obtained using Thompson (8.8%, p < 0.005) or Lubchenco (4.4%, p < 0.005)
      percentiles. However, the risk factors identified and the magnitude of the point
      estimates for odds ratios were similar regardless of the reference percentiles.
      This study shows a significant misclassification of newborns as small or adequate
      for gestational age that may affect individual prognosis, but this is not
      reflected in the type and the importance of detected risk factors at a group
      level.

PMID- 9254532
TI  - [Acute myocardial infarct in infants].
AB  - A retrospective study was made of 6 children, with nonsurgical-related acute
      myocardial infarction (AMI), between January 1987 and December 1994. The ratio
      for gender was 1 and mean age at AMI was 49 days, 4 cases being associated with
      congenital heart disease (Fallot's tetralogy, truncus arteriosus and DiGeorge
      syndrome, one case each, and anomalous origin of left coronary artery, 2 cases).
      Kawasaki disease and coronary embolisation from thrombosis of the renal vein
      occurred in the other 2 cases respectively. All developed congestive cardiac
      failure and cardiomegaly. In the ECG pathologic q waves with more than 35 msec
      occurred in all, and QT prolongation occurred in 3. Five children (83%) all with
      AMI in the anterior and lateral wall of the left ventricle died, death being
      related with cardiac mechanical failure and not with arrhythmias.

PMID- 9254533
TI  - [Acute infectious diarrhea in children].
AB  - Diarrhoea is defined either clinically or pathophysiologically. Some
      epidemiological issues are considered in a global as well as in a national
      perspective. The main etiologies and pathophysiological mechanisms are referred.
      Some important natural defenses against intestinal infection are pointed out.
      Clinical manifestations are briefly described. The main therapeutical guidelines
      are discussed. Breast milk is referred to as one of the most important preventive
      measures against acute infectious diarrhoea.

PMID- 9254534
TI  - [The prevention of insulin-dependent diabetes mellitus].
AB  - At the present time, there are markers which we can use to identify individuals
      with a high susceptibility of developing insulin-dependent diabetes mellitus
      (IDDM) years before the onset of the disease. Insulin-dependent diabetes mellitus
      is an autoimmune disease strongly associated with HLA antigens DR3 and DR4. In
      this manuscript, we discuss the usefulness of several markers, such as islet cell
      antibodies, insulin autoantibodies and glutamic acid decarboxylase antibodies, to
      identify individuals with a high susceptibility to IDDM before the disease is
      clinically evident. Monitoring first phase insulin release during intravenous
      glucose administration is a useful index of residual beta cell function that can
      be used to detect individuals who are close to insulin dependence. Several drugs
      have been used to prevent the development of IDDM. These include
      immunodepressors, anti-inflammatory agents, non-specific immunomodulators and
      free radical scavengers. Due to their toxicity, studies employing aziothioprine
      and cyclosporin were discontinued. Other agents, such as tetrandrin and
      lymphotoxin, are now restricted to non-human trials. Currently, two large-scale
      multicentric human trials, one in Europe using nicotinamide (European
      Nicotinamide Diabetes Intervention Trial, ENDIT) and the other in the USA using
      insulin (Diabetes Prevention Trial), are now in full activity and will test the
      benefits of these drugs in the prophylaxis of IDDM in highly susceptible
      individuals.

PMID- 9254536
TI  - [Curriculum planning. The direct way].
AB  - An attempt is being made in several Portuguese Medical Schools to reduce the
      Medical Course to five academic years. It will be easier and much more rigorous
      to base these changes on a detailed list of Educational Objectives. The choice of
      Educational Objectives must take into account the professional and social context
      surrounding the non-specialist physician (family doctor, general practitioner,
      etc), the background and maturity of the students, the manpower and resources of
      the Medical School and the results of the evaluation of the medical graduates as
      they finish their undergraduate training. This paper is an attempt to produce a
      list of Educational Objectives for undergraduate training in urology. Since we
      lack adequate information in relation to Portugal, we relied on epidemiological
      data from other countries as well as the experience obtained in similar attempts
      carried out in the USA.

PMID- 9254535
TI  - [Therapeutic angiography].
AB  - After a brief reference to the most important pioneers of angiography, the author
      describes the techniques performed, lesions treated and future perspectives. The
      following techniques are performed: embolizations, selective infusion of drugs,
      placement of inferior vena cava filter, removal of intra-vascular bodies,
      revascularisation techniques and porta-cava shunt. Reference was made to the
      following lesions treated: tumours, hemorrhages, arteriovenous malformations,
      hypersplenism, pulmonary embolism, varicocele, ischemic lesions and portal
      hypertension.

PMID- 9254537
TI  - [A systems approach to the hospital system].
AB  - The new pathology of the nineties and the management of hospital resources
      requires a new attitude and behaviour. The hospital system must satisfy the
      necessities and expectations of the population. The systemic approach to the
      hospital system provides a better understanding of the system and some possible
      answers.

PMID- 9254538
TI  - [The aspects of humanizing in hospitals for adults. We learn from pediatric
      experience!].
AB  - Since the late seventies, the Portuguese pediatric health services have gradually
      been accepting and desiring the presence of a family member during a child's
      hospital stay, due to the affective and psychological benefits thereof. This
      attitude was extended to include the emergency room, wards and intensive care
      units. In the majority of cases there is a perfect understanding between the
      health care team and the family member. It would be of the utmost importance for
      the humanization of the respective Services that the health care professionals of
      the adult hospitals, which are still very conservative with respect to this
      issue, should be encouraged to follow the Pediatric experience.

PMID- 9254539
TI  - [Diagnosis-related groups. Their contribution to an expanded discussion].
AB  - After defining the concept of medical activity quantification, the author focuses
      on the principle, objectives, advantages and inconveniences of DRGs. Describing
      the Portuguese experience, which was overall positive, the author ends by
      appealing for a greater discussion of all these concepts among physicians.

PMID- 9254540
TI  - [Statistics and medical decision making].
AB  - Statistics is the science that studies variability in all its forms and, in
      essence, is an instrument that allows us to analyze variable phenomena and detect
      small, but nevertheless important, differences. The instrumental character of
      this science made Statistics a fundamental tool for the study of biological and
      clinical phenomena, but the purpose of this discussion is to focus on the fact
      that Statistics, either directly or indirectly, is presently the basis of
      virtually all medical decision-making processes and, consequently, has had a
      major influence on clinical practice itself. Disease prevalence, the
      consideration of risk factors, for instance, which is information of great
      importance in the process of diagnosis, is obtained through studies that are
      based in statistical methodologies. It is, however, in the decision-intensive
      processes of selecting diagnostic examinations, choosing the best therapy and
      evaluating the prognostic implications, that Statistics have had a more direct
      impact on clinical practice. In modern Medicine, Statistics may no longer be seen
      as a set of techniques that are applied in scientific research. Rather,
      Statistics should be understood as the appropriate language for describing and
      discussing observed phenomena.

PMID- 9254541
TI  - [The Calmette-Guerin bacillus (BCG). An agent to consider in pediatric
      infection].
AB  - Complications occurring a long time after BCG vaccination in healthy children
      have been occasionally referred, despite being rare. Osteitis seems to be the
      most frequent of those complications; therefore it must be considered in the
      differential diagnosis of that sort of lesions. The authors report a case of a 15
      month old boy, previously healthy, who suffered an enlargement of the right foot
      for 3 weeks, unresponsive to antibiotics. The lesion revealed to be osteitis due
      to bacillus Calmette-Guerin, and abated after specific treatment.

PMID- 9254542
TI  - [A resurgence of rheumatic fever. New causes or old attitudes?].
AB  - Bearing in mind that in the last years there has been an increase in rheumatic
      fever episodes, the authors evaluate the cases recently observed in the
      department. The data of 3 children born and living in Portugal, the first known
      outbreak of rheumatic fever observed between June 93 and March 94, were examined.
      One case presented polyarthritis, another polyarthritis and carditis and the
      third chorea and carditis. In just one case was the diagnosis of rheumatic fever
      considered in the beginning, and over-all, failures in the diagnosis and
      treatment of tonsillitis, and in echocardiographic diagnosis were detected. In
      view of these examples, the authors conclude that the increasing incidence and
      morbidity of rheumatic fever is more probably due to forgetfulness of old
      attitudes than to new causes. Delay in the diagnosis and errors in secondary
      prophylaxis may influence long term results.

PMID- 9254544
TI  - HBO for necrotizing fasciitis.

PMID- 9254543
TI  - [Thermal colorectal lesions].
AB  - A case report of thermal burns of the rectum and colon in a 94-year-old woman.
      The thermal lesions were caused by a scalding water enema. Flexible sigmoidoscopy
      was useful in documenting the extension of the lesions and histology was helpful
      in documenting the diagnosis. The authors review the enema's complications.

PMID- 9254545
TI  - Varieties of elder abuse.

PMID- 9254546
TI  - What a nursing assistant knows.

PMID- 9254547
TI  - Clinical snapshot: gout.

PMID- 9254549
TI  - Proving nursing's value.

PMID- 9254548
TI  - Walk with me. Assuming the patient role can be a priceless lesson in empathy.

PMID- 9254550
TI  - Common questions about sex and sexuality in elders.

PMID- 9254551
TI  - Emergency contraception--parsimony and prevention in the medicine cabinet.

PMID- 9254552
TI  - Authors and authorship--reform or abolition?

PMID- 9254553
TI  - Statistics in the journal--significance, confidence, and all that.

PMID- 9254554
TI  - [The ultrasonic diagnosis of an early abnormal pregnancy].
AB  - During the period of January 1993 to February 1994, 70 pregnant women had an
      ultrasonic diagnosis of abnormal pregnancy. 111 ultrasound examinations were made
      -mean 1.6 of each woman. The ultrasonic diagnosis up to 70 women was: missed
      abortion--35 women (50%), blighted ovum--30 women (42.9%), other diagnosis--5
      women (7.1%). Histological examination of material was made with 64 women
      (91.4%). Comparing the ultrasonic diagnosis to histological results, authors do
      not recommend a final diagnosis before eight gestation week.

PMID- 9254555
TI  - [The premenstrual syndrome in adolescents].
AB  - The premenstrual syndrome is associated with the appearance of distressing
      somatic, physiological and behavioural symptoms at a certain phase of the
      menstrual cycle and has not been sufficiently studies with adolescents. The aim
      of this study is to determine the frequency, severity and period of appearance of
      the more important somatic and psychological symptoms characteristic of
      adolescents with PMS. The study includes 186 girls at an age between 16 and 18
      years monitored for the period of one year and four months. The most frequently
      met somatic symptom is headache (39%), the most frequent psychological one-
      irritability (46%). Sufficient attention is paid to the influence of the menarche
      and cigarette smoking in adolescents with PMS.

PMID- 9254556
TI  - [Sexual activity, contraception and abortions among teenagers in Bulgaria].
AB  - Sexual activity in adolescence, the pregnancies, abortions and deliveries, STDs
      and the decisive role of the information about sex and sexuality are questions
      with great importance nowadays. The aim of present study is to find the changes
      in the sexual activity among the adolescents, in their motivation in beginning
      the sexual life, information that they have about sex and sexuality, in unwanted
      pregnancies, deliveries and about abortions in the last five years, following our
      former study. We present the data obtained from an inquire of 432 schoolboys and
      girls (aged 17-18), from 263 girls, aged 13 to 18, admitted for interruption of
      unwanted pregnancy in the Univ. Ob. & Gyn. Hospital in Sofia, Bulgaria, as well
      as from 132 girls after delivery in adolescence.

PMID- 9254557
TI  - [Epidemiological studies of patients with genital chlamydiosis in Pleven
      District].
AB  - The authors aimed at conducting an epidemiological analysis of genital chlamydial
      infection among married couples with infertility problems, women with pelvic
      inflammatory disease and among patients with promiscuity and clinical symptoms of
      genital infection in the region of Pleven. They performed a prospective study for
      a six month period of time. 36 married couples with infertility problems and 66
      patients with promiscuity were included in the study. The authors conclude that
      genital chlamydiosis is a widely spread sexually transmitted disease among a
      large group of patients. Poor personal hygiene, poor education, young age, some
      professions which are a predisposition to promiscuity increase the risk of
      sexually transmitted diseases.

PMID- 9254559
TI  - [The relationship between simple and atypical endometrial hyperplasia and
      endometrial carcinoma].
AB  - The study was carried on 101 women in the perimenopause and postmenopause. The
      patients were divided into three groups, according to the results of the
      pathomorphological examination: I group--patients with simple hyperplasia; II
      group--patients with atypical hyperplasia; III group--patients with endometrial
      carcinoma. The simple hyperplasia predominates in the perimenopause, while the
      endometrial carcinoma was the most frequent cause for metrorrhagia in the
      postmenopausal women. When the endometrial carcinoma was combined with
      hyperplasia there were higher differentiation and less invasiveness of the
      endometrial carcinoma in these cases.

PMID- 9254560
TI  - [The adjuvant chemotherapy of N(-) patients with breast cancer--when is it
      indicated?].
AB  - The object of this research is determination the necessity of leading of adjuvant
      chemotherapy with patients with breast cancer without metastases in axillary
      lymph nodes (N(-)), with disadvantages other prognostic factors (T > 20 mm,
      estrogen receptors (-), II and III stage grading). Post-operative with 52 women
      with high risk of recedives or metastases had been performed polychemotherapy (39
      CMF and 13 FEC). Control group include 40 patients without adjuvant chemotherapy.
      Relapse are report with 6 of investigate and 8 of control group (pt > 0.05). The
      obtained results are discussed in connection with literature data.

PMID- 9254561
TI  - [The clinical picture of the fetal alcohol syndrome].
AB  - Six new cases of alcoholic embryopathy on newborn children are described. We
      found out that the mother suffers from chronicle alcoholism. The diagnosis fetal
      alcohol syndrome is made because there are the minimal diagnostically syndromes:
      prenatalis hypotrophia, microcephalia, mental retardation, face dysmorphism,
      cardinal anomalies. We have observed an unfolded clinical picture with added
      hypertrophia on the clitoris and anomalies of the kidneys on one of the children.
      With the description of the cases we direct obstetrician's and neonatologist's
      attention to this current in this moment medical problem.

PMID- 9254558
TI  - [Regional and systemic neoadjuvant chemotherapy in locally advanced carcinoma of
      the cervix uteri].
AB  - Neoadjuvant chemotherapy with bleomycin and Cisplastin was administered on ten
      patients with cervical cancer (IIB, IIIA, IIIB). On three successive days, five
      minutes after deep bilateral subcutaneous application of 100E Hylase in the
      medical surface of the lower third of the shin, 20 mg/msq of bleomycin was
      introduced slowly. The chemotherapeutic drug was absorbed by the lymph
      capillaries predominantly, and then transferred to the pelvic lymph nodes.
      Cisplastin was administered intravenously, at a dose of 50 mg/msq. Treatment was
      applied three times, third week. Remission was observed in 5 out of the 10 cases.

PMID- 9254562
TI  - [Hemorheological parameters in the prognosis of the risk of fetal retardation in
      pregnancy with arterial hypertension].
AB  - The haemorheological theory creates the notions of the interrelationship between
      the haemodynamic alterations in the blood flow and the whole-blood viscosity. The
      whole-blood viscosity is a variable parameter in close relation to the vessel
      geometry and blood flow rate, the blood plasma viscosity, the volume
      concentration of the blood cells, mostly of the red blood cells (the haematocrit)
      as well as to the hydrodynamically effective haemorheological phenomena of the
      aggregation and deformability of the erythrocytes. In the onward development of
      pregnancy in Bulgarian women with pre-eclamptic signs an increase of the
      haematocrit, the haemoglobin concentration and the erythrocyte aggregation were
      found. These data could be of benefit as reference point of possible risk
      conditions for the mother during the pregnancy advance and in the same time of
      manifestation a retardation and/or stillbirth or neonatal death.

PMID- 9254563
TI  - [The preimplantation diagnosis of genetic defects].

PMID- 9254564
TI  - [Amniotic fluid--an important factor in fetal development (a review of the
      literature)].

PMID- 9254565
TI  - [The relationship between the outcome of a free vaginal birth and the indications
      for a prior cesarean section].
AB  - The author sets up the task to analyse the correlation between the results of
      vaginal delivery and the indications for a previous Caesarean section. The work
      is done on the base of 740 deliveries in the Clinic of Obstetrics and Gynaecology
      in Stara Zagora. The author discusses the major indications for Caesarean
      delivery especially pelvis-fetal disproportion and makes the conclusion that this
      indication has not been set properly during the first Caesarean delivery because
      the women delivers even larger fetuses per vias naturales in the consequent
      pregnancies. The pelvio-fetal disproportion in pregnancy does not mean that the
      next pregnancies must be terminated by operation.

PMID- 9254566
TI  - [The advantages, disadvantages and sequelae of episiotomy and spontaneous tears
      of the perineum].

PMID- 9254568
TI  - [Rare locations of myoma--a case report].

PMID- 9254567
TI  - [The testicular feminization syndrome combined with disseminated
      hemangiomatosis].
AB  - It is described a new born child with many hemangiomas on the liver. It is made a
      karyogram to exclude. The possibility of chromosome disease. We fixed male
      karyotype 46 XY--syndrome Morris. We found out that it is a rare combination of
      testicular feminization with disseminated hemangiomatosis. After the medical
      treatment with high doses of cortisone the hemangiomas decreased their sizes.

PMID- 9254569
TI  - [A case of genital actinomycosis--the diagnostic difficulties].

PMID- 9254570
TI  - [A rare case of a kidney situated in the lesser pelvis. The diagnostic
      difficulties].
AB  - The minor aries to us an interesting case--woman, 30 years with two deliveries-at
      gynaecological examination in the polyclinic it is found a formation in the
      region of the left ovary. The laparotomy in this connection finds ectopic
      situated left kidney in the minor pelvis. The author calls attention to the
      differential diagnostic difficulties, which poses this casus to the practising
      gynaecologists and that it always must be thinking about this also on a large
      aspect.

PMID- 9254571
TI  - [Struma ovarii--a rare tumor in gynecological practice].
AB  - The authors present four cases of struma ovarii, observed a period of five years
      (1990-1995) in the Chair of Gynaecology and Obstetrics--Pleven. The literature
      data concerning this interesting problem was discussed in detail.

PMID- 9254572
TI  - [Temporary embryonic maturation in the tubes of heterologous species].

PMID- 9254573
TI  - [The treatment of vaginal candidiasis during pregnancy with a single dose of
      clotrimazole].
AB  - The author is describing their own clinical experience with the treatment of
      vaginal candidosis during pregnancy with the application of a single dose
      clotrimazole 500 mg (Canesten 1) with only one vaginal globule. In 77.5% of the
      pregnancy women is obtained a perfect result with disappearing of the clinical
      symptoms (pruritus, increasing bleeding, discomfort during excretion of urine)
      and negativisation of the microbiological results. The author is making the
      conclusion, that the treatment with a unique vaginal globule can be useful in
      light and acute cases of mycotic colpitis in pregnant patients. A recommendation
      is given for follow-up of the pregnant patients in the last 3-4 weeks of the
      pregnancy, for a candidosis check-up and prescription of an adequate treatment.

PMID- 9254575
TI  - [Standards for the determination of the physical development of newborn infants
      in the city of Plovdiv].
AB  - Using the method of the percentiles the author derives the referent values for
      the individual estimation of the newborns in the town of Plovdiv, using the
      following signs: height, body mass, head and chest circumferences. The referent
      values are derived according to sex. They can find an application for the
      practical work of the obstetricians and pediatricians in the town of Plovdiv.

PMID- 9254574
TI  - [The therapeutic potentials of the vaginal antimicrobial preparation
      Chlorchinaldin].
AB  - The aim of this study is the clinical testing of the vaginal wide-range,
      antimicrobial, quinolone--Chlorchinaldin/0,2/by POLFA, which has a strong
      antibacterial, antifungal, trichomonal and keratoplastic effect. The medicine was
      used on 43 patients with complaints of aggravated fluor. The clinical,
      colposcopic and microbiologic study showed: candidiasis--in 16 trichomoniasis--in
      8, bacterial vaginalis--in 3 and anaerobic vaginitis--in 2 patients. The rest of
      the women (14) had various aerobic microbial findings. The treatment was daily
      using one vaginal tablet, every night for 10 days. A control examination was
      carried out one week after the any of therapy. The results showed a positive
      clinical effect, since in 67.4% there were negative microbiological findings. The
      lack of effect in cases with bacterial vaginosis and anaerobic vaginitis was
      painted out. These results give reason to believe that the wide antimicrobial
      range of Chlorchinaldin B will be complementary to the currently used drugs in
      the treatment of vaginal infections.

PMID- 9254576
TI  - [An alternative method for treating headache after spinal anesthesia in cesarean
      section].
AB  - From pregnant women, delivered with section caesarean and spinal anaesthesia 22%
      36% have complained of headache. Its treatment is difficult. A group of 35
      pregnant women aged between 22-34 years have received headache after spinal
      anaesthesia for caesarean section. They were subjected to acupuncture in the
      points S8, Li4, G11,14, B10, GV14,20 by the scheme. The number of procedures
      varied between 1 and 3. The author reports the following results: headache passed
      in 30 women after 1 procedure, in 4--after 2 and in 1--after 3 procedures. The
      author concluded that the method is effective.

PMID- 9254577
TI  - [Birth injuries to the liver in deceased newborns in relation to the means of
      delivery].
AB  - The study includes all 151 deceased newborns with traumatic subcapsular
      haemorrhage of the liver for the 3-year period between 1992 and 1994 in the
      University Maternity Hospital "Maichin dom"--Sofia. We compared the frequency and
      the causes for the hepatic rupture and how they depend on the way of delivery. We
      established a significantly higher frequency in the group of neonates undergone
      breech delivery /17.2%/ then in the group with head presentations /5.7%/. In the
      last group 3 of neonates were born by caesarean section. We conclude that the
      breech presentation increases the risk of hepatic birth injuries. Other
      predisposing factors are the perinatal asphyxia and the immaturity.

PMID- 9254578
TI  - Local nasal immunotherapy. Proceedings of a satellite symposium to the XVI
      Congress of European Academy of Allergology and Clinical Immunology. Madrid, June
      1995.

PMID- 9254579
TI  - Choice of tracheal tube size for children: finger size or age-related formula?
AB  - A study was undertaken to compare the size of tracheal tube used for paediatric
      anaesthesia derived from either the diameter of the distal phalanx of the little
      or index finger, or from a standard formula (age in years/4 + 4.5 mm). The
      results showed that the diameter of the terminal phalanx was a poor predictor of
      the external diameter of the tube that provided the best fit. The mean (SD)
      diameters were 9.34 (1.02), 10.24 (1.23) and 7.56 (0.97) mm for the little
      finger, index finger and tracheal tube providing 'best fit', respectively. The
      formula provided a better correlation with the internal diameter of the chosen
      tracheal tube. The mean (SD) figures were 5.61 (0.75) and 5.70 (0.67) mm for the
      formula and the chosen tracheal tube, respectively. The use of the diameter of
      the terminal phalanx of either the little or the index finger is an unreliable
      measurement for the prediction of the tracheal tube size in paediatrics.

PMID- 9254580
TI  - [Age-dependent changes in the sub-epithelial blood supply to the bovine rumen].
AB  - Qualitative age-related changes in the structure and the position of
      subepithelial blood vessels in the bovine atrium ruminis were investigated on the
      electron microscopical level in 39 fetal, peri- and postnatal individuals as well
      as in adult animals of different ages. Standardized morphometrical methods were
      applied and the data were statistically evaluated. The distance between
      epithelium and capillary endothelium, the endothelial fenestration and the
      thickness of the endothelial wall as well as the endothelial-epithelial exchange
      sectors facing each other were distinctly a function of age. Crucial changes of
      these parameters were either finished until the sixth postnatal month and were
      pronounced during the period of feeding adaptation from milk to roughage or were
      not markedly influenced during this period. The degree of endothelial
      vesiculation showed individual variations but was not a function of age or
      feeding regime.

PMID- 9254581
TI  - Digestion of staphylococcal enterotoxin by Bacillus natto.
AB  - Cooked rice contaminated with staphylococcal enterotoxin A (SEA) was mixed with
      'natto', a Bacillus natto fermented soybean food, and the mixture was incubated
      at 37 degrees C for 1 h. Reversed passive latex agglutination (RPLA) tests
      performed on the mixture revealed that the RPLA titer against SEA was
      significantly reduced after incubation. Subsequent analytical tests showed that
      the SEA protein molecule was fragmented to small peptides by an extracellular
      protease, subtilisin, produced by B. natto. The proteolytic activity of B. natto
      was also found to be effective against other types of staphylococcal
      enterotoxins.

PMID- 9254582
TI  - [The 50th anniversary of the State Scientific Center on Antibiotics (pages from
      its history)].

PMID- 9254583
TI  - [A conjugate of ristomycin A ristosaminylaglycon-polymyxin B: the spectrum of its
      antimicrobial action and its membranolytic activity].
AB  - Antimicrobial activity of a conjugate based on two antibiotics, i.e. ristomycin A
      and polymyxin B was studied. The conjugate was shown to have a broad
      antimicrobial spectrum. In concentrations of 5 to 30 micrograms/ml it inhibited
      the growth of gram-positive and gram-negative bacteria and in concentrations of 5
      to 40 micrograms/ml it inhibited the growth of the pathogenic clinical strains.
      An insignificant membranolytic action of the conjugate with respect to membranes
      of the susceptible bacteria and no hemolytic action on human red blood cells were
      detected.

PMID- 9254584
TI  - [Homeostatic changes in monkeys in a model of glanders].
AB  - Some aspects of homeostasis impairment in monkeys infected with Pseudomonas
      mallei were investigated. The levels of the hormonal shifts, complement
      components, beta 2-microglobulin and prostaglandins evident of the infection
      severity were estimated. The pathomorphological profiles of various forms of
      malleus in the primates were studied.

PMID- 9254585
TI  - [The science of antibiotics: a retrospective and view to the future].

PMID- 9254586
TI  - [The possibility of using the mycelial wastes from the production of antifungal
      antibiotics as additives to lubricating oils].
AB  - Antiwear and antitear properties of mycelial waste from production of antifungal
      antibiotics i.e. levorin, nystatin, mycoheptin, amphotericin B and griseofulvin
      were studied. It was shown that the waste mycelium from griseofulvin production
      had the best antiwear and antitear characteristics due to a higher percentage of
      phosphorus and sulphur in it as compared to the mycelial waste from production of
      the other antibiotics.

PMID- 9254587
TI  - [The 75th anniversary of the discovery of lysozyme].

PMID- 9254588
TI  - [Nikolai Aleksandrovich Krasil'nikov (on the centenary of his birth)].

PMID- 9254589
TI  - [A survey of the materials from the 7th International Congress on Infectious
      Diseases].

PMID- 9254590
TI  - [Rifabutin--a new antituberculous antibiotic].

PMID- 9254591
TI  - Cytoplasmic disposition of aspartate 821 in anion exchanger from human
      erythrocytes.
AB  - The location with respect to the plasma membrane of aspartate 821 in erythrocytic
      anion exchanger has been determined by labeling inside-out vesicles and intact
      erythrocytes with impermeant reagents and following the outcome by site-directed
      immunochemistry. Intact erythrocytes and inside-out vesicles in the same
      container were vectorially modified with 1-ethyl-3-[3
      (trimethylammonio)propyl]carbodiimide and [35S]sulfanilic acid. The inside-out
      vesicles were separated from the erythrocytes by differential centrifugation, and
      both the vesicles and membranes made from the erythrocytes were stripped with
      alkali and digested with trypsin to liberate from each sample the peptide
      YHPDVPYVK containing aspartate 821. The tryptic digests were passed over an
      immunoadsorbent specific for peptides with the amino-and carboxy-terminal
      sequences YHPD- and -PYVK. Specifically bound peptides were eluted with acid, and
      the eluates were pooled and submitted to high-pressure liquid chromatography. A
      peak of absorbance at 229 nm corresponding to the peptide YHPDVPYVK was present
      in chromatograms of samples from both the inside-out vesicles and the intact
      erythrocytes. Another peak that displayed absorbance at 229 and 250 nm,
      corresponding to the peptide YHP(p-[35S]sulfo-beta-aspartanilide)VPYVK, was
      observed in the chromatogram of the sample from the inside-out vesicles but not
      in the chromatogram of the sample from the erythrocytes. This peak had associated
      with it a large number of counts per minute of [35S]sulfur, whereas no counts per
      minute of [35S]sulfur above background were detected on the chromatogram of the
      sample from the erythrocytes. The incorporation of [35S]sulfanilic acid into
      aspartate 821 of anion exchanger in inside-out vesicles was at least 10-fold
      greater than the incorporation of [35S]sulfanilic acid into aspartate 821 of
      anion exchanger in erythrocytes when the two preparations were labeled in the
      same solution. These results demonstrate that aspartate 821, found between two
      hydrophobic segments in the sequence of anion exchanger, is located on the
      cytoplasmic surface of this membrane-spanning protein.

PMID- 9254592
TI  - A classical enzyme active center motif lacks catalytic competence until modulated
      electrostatically.
AB  - The cysteine proteinase superfamily is a source of natural structural variants of
      value in the investigation of mechanism. It has long been considered axiomatic
      that catalytic competence of these enzymes mirrors the generation of the
      ubiquitous catalytic site imidazolium-thiolate ion pair. We here report
      definitive evidence from kinetic studies supported by electrostatic potential
      calculations, however, that at least for some of these enzymes the ion pair state
      which provides the nucleophilic and acid-base chemistry is essentially fully
      developed at low pH where the enzymes are inactive. Catalytic competence requires
      an additional protonic dissociation with a common pKa value close to 4 possibly
      from the Glu50 cluster to control ion pair geometry. The pH dependence of the
      second-order rate constant (k) for the reactions of the catalytic site thiol
      groups with 4,4'-dipyrimidyl disulfide is shown to provide the pKa values for the
      formation and deprotonation of the (Cys)-S-/(His)-Im+H ion pair state. Analogous
      study of the reactions with 2,2'-dipyridyl disulfide reveals other kinetically
      influential ionizations, and all of these pKa values are compared with those
      observed in the pH dependence of kcat/Km for the catalyzed hydrolysis of N
      acetylphenylalanylglycine 4-nitroanilide. The discrepancy between the pKa value
      for ion pair formation and the common pKa value close to 4 related to generation
      of catalytic activity is particularly marked for ficin (pKa 2.49 +/- 0.02) and
      caricain (pKa 2.88 +/- 0.02) but exists also for papain (pKa 3.32 +/- 0.01).

PMID- 9254593
TI  - The crystal structure of citrate synthase from the hyperthermophilic archaeon
      pyrococcus furiosus at 1.9 A resolution,.
AB  - The crystal structure of the closed form of citrate synthase, with citrate and
      CoA bound, from the hyperthermophilic Archaeon Pyrococcus furiosus has been
      determined to 1.9 A. This has allowed direct structural comparisons between the
      same enzyme from organisms growing optimally at 37 degrees C (pig), 55 degrees C
      (Thermoplasma acidophilum) and now 100 degrees C (Pyrococcus furiosus). The three
      enzymes are homodimers and share a similar overall fold, with the dimer interface
      comprising primarily an eight alpha-helical sandwich of four antiparallel pairs
      of helices. The active sites show similar modes of substrate binding; moreover,
      the structural equivalence of the amino acid residues implicated in catalysis
      implies that the mechanism proceeds via the same acid-base catalytic process.
      Given the overall structural and mechanistic similarities, it has been possible
      to make detailed structural comparisons between the three citrate synthases, and
      a number of differences can be identified in passing from the mesophilic to
      thermophilic to hyperthermophilic citrate synthases. The most significant of
      these are an increased compactness of the enzyme, a more intimate association of
      the subunits, an increase in intersubunit ion pairs, and a reduction in
      thermolabile residues. Compactness is achieved by the shortening of a number of
      loops, an increase in the number of atoms buried from solvent, an optimized
      packing of side chains in the interior, and an absence of cavities. The intimate
      subunit association in the dimeric P. furiosus enzyme is achieved by greater
      complementarity of the monomers and by the C-terminal region of each monomer
      folding over the surface of the other monomer, in contrast to the pig enzyme
      where the C-terminus has a very different fold. The increased number of
      intersubunit ion pairs is accompanied by an increase in the number involved in
      networks. Interestingly, all loop regions in the P. furiosus enzyme either are
      shorter or contain additional ion pairs compared with the pig enzyme. The
      possible relevance of these structural features to enzyme hyperthermostability is
      discussed.

PMID- 9254594
TI  - Interactions of deglycosylated cobalt(III)-pepleomycin (green form) with DNA
      based on NMR structural studies,.
AB  - Pepleomycin (PEP)1 is a metalloglycopeptide antitumor antibiotic that has
      improved pharmacological properties than does bleomycin (BLM). Both PEP and BLM
      bind to and degrade DNA in a sequence-selective manner. The binding interactions
      of HO2--Co(III)-CodPEP (CodPEP) with CGTACG have been studied by 2D NMR and
      molecular modeling. Inspection of the 2D-NMR data revealed 60 notable
      intermolecular NOEs between CodPEP and CGTACG which place the drug's metal
      binding domain and peptide linker in the minor groove of the DNA close to G8 and
      T9. On the basis of the NOEs, the drug's DNA binding domain is located close to
      the T9.A4 and A10.T3 base pairs. Intercalation of the bithiazole tail between
      these base pairs is indicated by the loss of DNA symmetry upon complexation with
      CodPEP, by a break in the sequential connectivity at the TpA steps, and by the
      upfield shift of the bithiazole H-H5 and H-H5' proton resonances. Intercalation
      of the bithiazole moiety unfolds the CodPEP molecule and exposes its
      hydroperoxide group to the DNA. The hydroperoxide group in the refined model of
      CodPEP-CGTACG is close to the C4' proton of T9, consistent with cleavage at this
      position. The NOE pattern between the pyrimidine ring of CodPEP and G8 of DNA
      suggests a specific pairing recognition via hydrogen bonds between these groups,
      thus establishing a 5'-GT-3' sequence preference. The structural elucidation of
      the free CodPEP and CoPEP [Caceres-Cortes et al. (1997) Eur. J. Biochem. 244, 818
      828], and of the complex of CodPEP-CGTACG afford a plausible mechanism for the
      recognition and its subsequent cleaving of DNA by the drug. The process involves
      the unfolding of the compact CodPEP, recognition of a guanine base using the
      metal binding domain, threading of the bithiazole tail between base pairs, and
      finally positioning of the HO2- group close to the T or C found 3' to the
      specific G site.

PMID- 9254595
TI  - Thermodynamic and structural analysis of phosphotyrosine polypeptide binding to
      Grb2-SH2.
AB  - A thermodynamic analysis using isothermal titration calorimetry (ITC) has been
      performed to examine the binding interaction between the SH2 (Src homology 2)
      domain of growth factor receptor binding protein 2 (Grb2-SH2) and one of its
      phosphotyrosine (pY) polypeptide ligands. Interaction of the Shc-derived
      phosphotyrosine hexapeptide Ac-SpYVNVQ-NH2 with Grb2-SH2 was both enthalpically
      and entropically favorable (DeltaH = -7.55 kcal mol-1, -TDeltaS = -1.46 kcal mol
      1 , DeltaG = -9.01 kcal mol-1, T = 20 degrees C). ITC experiments using five
      alanine-substituted peptides were performed to examine the role of each side
      chain in binding. The results were consistent with homology models of the Grb2
      SH2-Shc hexapeptide complex which identified several possible hydrogen bonds
      between Grb2-SH2 and the phosphotyrosine and conserved asparagine(+2) side chains
      of the Shc hexapeptide. These studies also demonstrated that the hydrophobic
      valine(+1) side chain contributes significantly to the favorable entropic
      component of binding. The thermodynamic and structural data are consistent with a
      Grb2-SH2 recognition motif of pY-hydrophobic-N-X (where X is any amino acid
      residue). The measured heat capacity of binding (DeltaCp = -146 cal mol-1 K-1)
      was very similar to computed values using semiempirical estimates (DeltaCp = -106
      to -193 cal mol-1 K-1) derived from apolar and polar accessible surface area
      values calculated from several homology models of the Grb2-SH2-Shc hexapeptide
      complex. The homology model which most closely reproduced the measured DeltaCp
      value is also the model which had the lowest RMS deviation from the subsequently
      determined crystal structure. Calculations based on the thermodynamic data and
      these semiempirical estimates indicated that the binding event involves burial of
      nearly comparable apolar (677 A2) and polar (609 A2) surface areas.

PMID- 9254596
TI  - High-resolution NMR structure and backbone dynamics of the Bacillus subtilis
      response regulator, Spo0F: implications for phosphorylation and molecular
      recognition.
AB  - NMR has been employed for structural and dynamic studies of the bacterial
      response regulator, Spo0F. This 124-residue protein is an essential component of
      the sporulation phosphorelay signal transduction pathway in Bacillus subtilis.
      Three-dimensional 1H, 15N, and 13C experiments have been used to obtain full side
      chain assignments and the 1511 distance, 121 dihedral angle, and 80 hydrogen
      bonding restraints required for generating a family of structures (14 restraints
      per residue). The structures give a well-defined (alpha/beta)5 fold for residues
      4-120 with average rms deviations of 0.59 A for backbone heavy atoms and 1.02 A
      for all heavy atoms. Analyses of backbone 15N relaxation measurements demonstrate
      relative rigidity in most regions of regular secondary structure with a
      generalized order parameter (S2) of 0.9 +/- 0.05 and a rotational correlation
      time (taum) of 7.0 +/- 0.5 ns. Loop regions near the site of phosphorylation have
      higher than average rms deviation values and T1/T2 ratios suggesting significant
      internal motion or chemical exchange at these sites. Additionally, multiple
      conformers are observed for the beta4-alpha4 loop and beta-strand 5 region. These
      conformers may be related to structural changes associated with phosphorylation
      and also indicative of the propensity this recognition surface has for
      differential protein interactions. Comparison of Spo0F structural features to
      those of other response regulators reveals subtle differences in the orientations
      of secondary structure in the putative recognition surfaces and the relative
      charge distribution of residues surrounding the site of phosphorylation. These
      may be important in providing specificity for protein-protein interactions and
      for determining the lifetimes of the phosphorylated state.

PMID- 9254597
TI  - DNA bending by GCN4 mutants bearing cationic residues.
AB  - Transcription activation is thought to require DNA bending to promote the
      interaction of upstream activators and the basal transcription machinery.
      Previous experiments have shown that some members of the bZIP family of DNA
      binding proteins bend DNA, while others do not. We are exploring the possibility
      that electrostatic effects play a role in these differences. The yeast bZIP
      transcription factor GCN4 does not induce DNA bending in vitro. Substitution of
      basic residues for three neutral amino acids of GCN4 confers the ability to bend
      DNA. This result is consistent with a model of induced DNA bending wherein excess
      positive charge in proximity to one face of the double helix neutralizes local
      phosphate diester anions resulting in a laterally asymmetric charge distribution
      along the DNA. Previous data suggest that such an unbalanced charge distribution
      results in collapse of the DNA toward the neutralized surface. Interpretations of
      the present data are discussed. Our result supports the hypothesis that
      electrostatic interactions can play a key role in DNA bending by bZIP proteins.

PMID- 9254598
TI  - Electrostatic mechanism for DNA bending by bZIP proteins.
AB  - Biology is replete with examples of protein-induced DNA bending, yet the forces
      responsible for bending have been neither established nor quantified. Mirzabekov
      and Rich proposed in 1979 that asymmetric neutralization of the anionic
      phosphodiester backbone by basic histone proteins could provide a thermodynamic
      driving force for DNA bending in the nucleosome core particle [Mirzabekov, A. D.,
      & Rich, A. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 1118-1121]. Strauss and Maher
      lent support to this proposal in 1994 by demonstrating that replacement of six
      proximal phosphate residues with neutral methylphosphonates resulted in DNA bent
      spontaneously toward the neutralized face [Strauss, J. K., & Maher, L. J., III
      (1994) Science 266, 1829-1834; Strauss, J. K., Prakash, T. P., Roberts, C.,
      Switzer, C., & Maher, L. J., III (1996) Chem. Biol. 3, 671-678; Strauss, J. K.,
      Roberts, C.; Nelson, M. G.; Switzer, C., & Maher, J. L., III (1996) Proc. Natl.
      Acad. Sci. U.S.A. 93, 9515-9520]. Here it is shown that bZIP proteins bend DNA
      via a mechanism involving direct contacts between one or two basic side chains
      and a symmetry-related pair of unique, nonbridging phosphate oxygens. The
      locations of these phosphates provide direct experimental support for a protein
      induced bending mechanism based on asymmetric charge neutralization. This
      straightforward mechanism is compatible with many DNA-recognition motifs and may
      represent a general strategy for the assembly of protein-DNA complexes of defined
      stereochemistries.

PMID- 9254599
TI  - Structures of competitive inhibitor complexes of protocatechuate 3,4-dioxygenase:
      multiple exogenous ligand binding orientations within the active site.
AB  - Protocatechuate 3,4-dioxygenase (3,4-PCD) catalyzes the oxidative ring cleavage
      of 3,4-dihydroxybenzoate to produce beta-carboxy-cis, cis-muconate. Crystal
      structures of Pseudomonas putida3,4-PCD [quaternary structure of
      (alphabetaFe3+)12] complexed with seven competitive inhibitors [3
      hydroxyphenylacetate (MHP), 4-hydroxyphenylacetate (PHP), 3-hydroxybenzoate
      (MHB), 4-hydroxybenzoate (PHB), 3-fluoro-4-hydroxybenzoate (FHB), 3-chloro-4
      hydroxybenzoate (CHB), and 3-iodo-4-hydroxybenzoate (IHB)] are reported at 2.0
      2.2 A resolution with R-factors of 0. 0.159-0.179. The inhibitors bind in a
      narrow active site crevasse lined with residues that provide a microenvironment
      that closely matches the chemical characteristics of the inhibitors. This results
      in as little as 20% solvent-exposed surface area for the higher-affinity
      inhibitors (PHB, CHB, and FHB). In uncomplexed 3,4-PCD, the active site Fe3+ is
      bound at the bottom of the active site crevasse by four endogenous ligands and a
      solvent molecule (Wat827). The orientations of the endogenous ligands are
      relatively unperturbed in each inhibitor complex, but the inhibitors themselves
      bind to or near the iron in a range of positions, all of which perturb the
      position of Wat827. The three lowest-affinity inhibitors (MHP, PHP, and IHB)
      yield distorted trigonal bipyramidal iron coordination geometry in which the
      inhibitor C4-phenolate group displaces the solvent ligand. MHB binds within the
      active site, but neither its C3-OH group nor the solvent molecule binds to the
      iron. The C4-phenolate group of the three highest-affinity inhibitors (PHB, CHB,
      and FHB) coordinates the Fe3+ adjacent to Wat827, resulting in a shift in its
      position to yield a six-coordinate distorted octahedral geometry. The range of
      inhibitor orientations may mimic the mechanistically significant stages of
      substrate binding to 3, 4-PCD. The structure of the final substrate complex is
      reported in the following paper [Orville, A. M., Lipscomb, J. D., & Ohlendorf, D.
      H. (1997) Biochemistry 36, 10052-10066].

PMID- 9254601
TI  - In vitro and in vivo redox states of the Escherichia coli periplasmic
      oxidoreductases DsbA and DsbC.
AB  - DsbC is a periplasmic protein of Escherichia coli that was previously identified
      by a genetic selection that rescued sensitivity to dithiothreitol in Tn10
      mutagenized cells. The Erwinia chrysanthemi dsbC gene was identified in a
      previous genetic screen to restore motility in a dsbA null strain. In order to
      analyze the biochemical role of E. coli DsbC, the protein was overexpressed,
      purified, and compared with DsbA in terms of disulfide isomerization, thiol
      oxidation, and in vivo redox state. In vitro, DsbC and DsbA have an equivalent
      kcat for disulfide isomerization with the model substrate, misfolded insulin-like
      growth factor-1. However, DsbA is a more effective oxidant than DsbC of protein
      dithiols. In vivo, DsbA is found exclusively in the oxidized state in wild-type
      strains grown in rich media. On the other hand, in vivo DsbC has one pair of
      cysteines oxidized and one pair reduced. DsbD is required to maintain this
      reduced pair of cysteines, confirming previous genetic results. A dsbC deletion
      strain showed decreases in the production of some, but not all, heterologous
      proteins containing multiple disulfide bonds. Notably, those proteins affected by
      the dsbC deletion do not have the cysteines paired consecutively.

PMID- 9254600
TI  - Crystal structures of substrate and substrate analog complexes of protocatechuate
      3,4-dioxygenase: endogenous Fe3+ ligand displacement in response to substrate
      binding.
AB  - Protocatechuate 3,4-dioxygenase (3,4-PCD) utilizes a ferric ion to catalyze the
      aromatic ring cleavage of 3,4-dihydroxybenzoate (PCA) by incorporation of both
      atoms of dioxygen to yield beta-carboxy-cis, cis-muconate. The crystal structures
      of the anaerobic 3,4-PCD.PCA complex, aerobic complexes with two heterocyclic PCA
      analogs, 2-hydroxyisonicotinic acid N-oxide (INO) and 6-hydroxynicotinic acid N
      oxide (NNO), and ternary complexes of 3,4-PCD.INO.CN and 3,4-PCD. NNO.CN have
      been determined at 2.1-2.2 A resolution and refined to R-factors between 0.165
      and 0.184. PCA, INO, and NNO form very similar, asymmetrically chelated complexes
      with the active site Fe3+ that result in dissociation of the endogenous axial
      tyrosinate Fe3+ ligand, Tyr447 (147beta). After its release from the iron, Tyr447
      is stabilized by hydrogen bonding to Tyr16 (16alpha) and Asp413 (113beta) and
      forms the top of a small cavity adjacent to the C3-C4 bond of PCA. The equatorial
      Fe3+ coordination site within this cavity is unoccupied in the anaerobic 3,4
      PCD.PCA complex but coordinates a solvent molecule in the 3,4-PCD.INO and 3,4
      PCD.NNO complexes and CN- in the 3,4-PCD.INO.CN and 3,4-PCD.NNO.CN complexes.
      This shows that an O2 analog can occupy the cavity and suggests that
      electrophilic O2 attack on PCA is initiated from this site. Both the dissociation
      of the endogenous Tyr447 and the expansion of the iron coordination sphere are
      novel features of the 3,4-PCD. substrate complex which appear to play essential
      roles in the activation of substrate for O2 attack. Together, the structures
      presented here and in the preceding paper [Orville, A. M., Elango, N. , Lipscomb,
      J. D., & Ohlendorf, D. H. (1997) Biochemistry 36, 10039-10051] provide atomic
      models for several steps in the reaction cycle of 3,4-PCD and related Fe3+
      containing dioxygenases.

PMID- 9254602
TI  - Lateral packing of the pancreatic lipase cofactor, colipase, with
      phosphatidylcholine and substrates.
AB  - The interaction of the pancreatic lipase cofactor colipase with a
      diacylphosphatidylcholine, acylglycerols, and free fatty acid was investigated by
      monitoring its adsorption to monomolecular lipid films. Surface pressure and
      colipase surface concentration were measured as a function of the initial lipid
      concentration and composition. Colipase adsorbs to a level of 28-30 pmol/cm2 to
      form a close-packed monolayer of protein and interacts strongly with all lipids
      when the lipid chain:colipase ratio is </=3. Consideration of the size difference
      between the protein and acyl groups suggests that in this regime the lipid is
      occupying the voids between tightly packed protein molecules. At lipid
      chain:colipase ratios >3, the triacylglycerol is excluded from the monolayer
      phase. Phosphatidylcholine, diacylglycerols, and free fatty acid remain in the
      monolayer phase up to </=25 lipid chain:colipase ratios. Geometrically over this
      range of compositions, the colipase molecules should be separated by up to 0-2
      acyl chains. At higher lipid chain:colipase ratios, diacylglycerols are likely
      excluded from the monolayer phase. Anomalous behavior is observed with the fatty
      acid which at lipid chain:colipase ratios >25 induces higher levels of colipase
      adsorption than at lower ratios. This suggests the formation of a novel structure
      involving fatty acid and/or colipase. Phosphatidylcholine also remains in the
      interface at lipid chain:colipase ratios >3 but shows little additional
      interaction with colipase. However, fluorescence microscopy suggests that the
      phosphatidylcholine and colipase are miscible in the interface. The specificity
      demonstrated in this study suggests that colipase may regulate the type of
      surfaces to which colipase and, hence, lipase bind and may control the species
      distribution of substrate to which bound lipase is exposed.

PMID- 9254603
TI  - Importance of phospholipid in the folding and conformation of
      phosphatidylinositol transfer protein: comparison of apo and holo species.
AB  - The significance of noncovalently bound phospholipid as a structural component of
      phosphatidylinositol transfer protein (PITP) and its role in acquisition and
      maintenance of the native conformation of the protein have been addressed by
      studying the refolding of PITP after exposure to 6 M guanidinium chloride
      (GdnCl). Protein conformations were characterized by (1) the intrinsic tryptophan
      fluorescence, circular dichroism, and absorbance spectroscopy, (2) the degree of
      binding of the fluorescent probe 1,8-ANS, and (3) limited proteolytic digestion.
      When the GdnCl concentration was reduced 100-fold by rapid dilution at 25 degrees
      C, practically all of the native transfer activity was regained within 20 min.
      Endogenous phospholipid demonstrated a strong interaction with the native PITP.
      Separation of the phospholipid from the protein by chromatography on a lipophilic
      matrix was achieved only under denaturing conditions and resulted in spontaneous
      oxidation of the apo-protein, accompanied by almost complete loss of recoverable
      transfer activity. Under reducing conditions, however, apo-PITP recovered more
      than 80% of the native transfer activity and was similar to holo-PITP in the
      kinetics of phospholipid transfer. Renatured apo-PITP demonstrated a significant
      relaxation of the tertiary structure, compared to native and renatured holo-PITP.
      Incubation of apo-PITP with phospholipid vesicles resulted in a more compact
      protein conformation. We conclude that the polypeptide can spontaneously fold to
      a native-like conformation, sufficient for interaction with a lipid membrane and
      acquisition of a phospholipid ligand. Binding of a phospholipid ligand brings
      about the final adjustments of protein conformation to the more compact native
      structure.

PMID- 9254604
TI  - Allosteric activation of phosphatidylinositol-specific phospholipase C: specific
      phospholipid binding anchors the enzyme to the interface.
AB  - Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus
      thuringiensis exhibits 'interfacial activation' toward the water-soluble
      substrate myo-inositol 1,2-(cyclic)phosphate [Zhou et al. (1997) Biochemistry 36,
      347-355]. The activation of PI-PLC enzyme is optimal with PC or PE interfaces.
      NMR experiments (TRNOE and 31P line width analyses) were carried out to
      investigate the interaction of PI-PLC with activator amphiphiles. These studies
      showed that the enzyme had high affinity for phosphatidylcholine (or PE)
      molecules with dissociation constants of 0.5 and 0.3 mM for diC6PC and diC7PC,
      respectively. TRNOE cross-peaks of bound PC were confirmed to represent
      intramolecular relaxation pathways using partially perdeuterated PC molecules
      consistent with a single molecule binding tightly. The large activation by a PC
      interface can be explained by a single PC molecule binding specifically to PI-PLC
      and anchoring the enzyme-lipid complex to the interface. Other interfaces, such
      as micellar diC8PS, can activate PI-PLC about 2-3-fold; however, the monomers of
      these detergents showed little affinity for the enzyme as measured by TRNOE or
      31P NMR line widths. The 3.6-fold activation produced by polymerized vesicles of
      1,2-bis[12-(lipoyloxy)dodecanoyl]-sn-glycero-3-phosphocholine (compared to the 15
      fold activation generated by nonpolymerized PC vesicles) was comparable to the
      nonspecific activation of other detergents. This confirmed that single-PC
      molecule binding was allosteric and anchored the enzyme in the interface. The
      conformation of interfacially activated enzyme is discussed in term of the
      stabilization of a critical surface loop and helix B observed with weak intensity
      in the X-ray crystal structure.

PMID- 9254605
TI  - Converting trypsin to chymotrypsin: structural determinants of S1' specificity.
AB  - Trypsin and chymotrypsin differ strikingly in substrate specificities despite
      great similarity in their primary and tertiary structures. This work analyzes the
      role of two surface loops, loop 40 and loop 60, as structural determinants of the
      specificity of the S1'-subsite in chymotrypsin and trypsin. Chymotrypsin prefers
      P1' Arg/Lys residues, while trypsin prefers hydrophobic P1' residues. We replaced
      loop 40 and loop 60 in trypsin with their chymotrypsin counterparts. These
      mutations do not affect the S1 specificity and catalytic activity of trypsin. The
      S1' specificity was analyzed by monitoring acyl-transfer reactions to 16 amino
      acid amides. The exchange of loop 40 does not affect the S1' specificity. In
      contrast, the replacement of loop 60 causes a loss of specificity for P1'
      Met/Ile/Leu. Combining both mutations reconstitutes a chymotrypsin-like S1'
      specificity. The specificity for Arg-NH2 increases 3-fold while the preferences
      for Met-NH2 and Ile-NH2 decrease 4- and 8-fold, respectively. Therefore, P1'
      Arg/Met discrimination changes by factor 12 and P1'-Arg/Ile discrimination
      changes by factor 24. Thus, loop 40 and loop 60 act synergistically to determine
      S1' specificity in trypsin and chymotrypsin.

PMID- 9254606
TI  - Effect of a covalently attached synergistic anion on chelator-mediated iron
      release from ovotransferrin: additional evidence for two concurrent pathways.
AB  - The mechanism by which the iron-transport protein transferrin releases its iron
      in vivo is presently unclear. In vitro studies have implicated two concurrent
      chelator-mediated iron-release pathways: one which is hyperbolic in nature,
      involving a conformational change in the protein as a rate limiting step, and a
      second which has been proposed to be first-order in nature and to involve initial
      release of a synergistic anion. We have examined the effect that an affinity
      label analog of the synergistic anion has on chelator-mediated iron-release from
      this protein. A covalently attached anion would inhibit iron-release via any
      pathway in which anion release is a prerequisite to iron release. The present
      investigation examined the effect that the covalently attached anion had on iron
      release to pyrophosphate (PPi) and N, N-bis(phosphonomethyl)glycine (DPG), two
      chelators which are believed to utilize both pathways concurrently. Results show
      that when the affinity-label anion is utilized, strictly hyperbolic data are
      obtained, with similar observed kmax values. This is strong support for the
      hypothesis of a common, chelator-independent rate-limiting step for the one
      available pathway. These results also support strongly the hypothesis that
      synergistic anion removal is a prerequisite step to iron-release via the second
      pathway.

PMID- 9254607
TI  - Constitutive activation of the m5 muscarinic receptor by a series of mutations at
      the extracellular end of transmembrane 6.
AB  - The m5 muscarinic acetylcholine receptor was constitutively activated by a wide
      range of amino acid substitutions at a residue (serine 465) that is positioned at
      the junction of the sixth transmembrane domain and the extracellular loop. Of 13
      substitutions tested, 11 produced significant increases in constitutive activity.
      Replacement of serine 465 with large (phenylalanine and valine) or basic residues
      (arginine and lysine) increased the constitutive activity of the receptor to
      between 55 and 110% of the maximum response of the wild-type receptor to the
      agonist carbachol. Other substitutions (e.g., cysteine and leucine) increased the
      constitutive activity to an intermediate level (30%), while small and acidic
      residues (glycine, aspartate, and glutamate) caused small or insignificant
      increases. The increase in the constitutive activity of each mutant receptor
      correlated with an increase in the potency of carbachol in both binding and
      functional assays, with the most constitutively activated receptors showing a 40
      fold decrease in the EC50 of carbachol. The negative antagonist atropine bound to
      and reversed the constitutive activity of all mutant receptors with equal
      potency. These data were fitted to a two-state model of receptor function. The
      data are consistent with the primary effect of substitutions to serine 465 being
      to selectively destabilize the inactive state of the receptor, thus favoring
      formation of the active state in the absence of agonists. Our data strongly
      support this two-state model of receptor function and identify a critical role of
      this domain in the activation of muscarinic receptors.

PMID- 9254608
TI  - Phosphorylation of serine 392 stabilizes the tetramer formation of tumor
      suppressor protein p53.
AB  - Tumor suppressor protein p53 is a tetrameric phosphoprotein that activates
      transcription from several cell cycle regulating genes in response to DNA damage.
      Tetramer formation is critical to p53's ability to activate transcription;
      however, posttranslational modifications and protein stabilization also
      contribute to p53's ability to activate transcription. To determine if
      phosphorylation affects tetramer formation, we synthesized phosphopeptides
      corresponding to residues 303-393 of human p53, which includes the domain
      responsible for tetramer formation. Phosphate was chemically incorporated at
      Ser315, Ser378, or Ser392 and also at both Ser315 and Ser392. Equilibrium
      ultracentrifugal analyses showed that phosphorylation at Ser392 increased the
      association constant for reversible tetramer formation nearly 10-fold.
      Phosphorylation of either Ser315 or Ser378 had little effect on tetramer
      formation, but phosphorylation of Ser315 largely reversed the effect of
      phosphorylation at Ser392. Analyses by calorimetry demonstrated that
      phosphorylation may influence subunit affinity (and, in turn, DNA binding) by an
      enthalpy-driven process, possibly between the C-terminal residues and the region
      immediately adjacent to Ser315. The Kd for the tetramer-monomer transition of the
      unphosphorylated p53 C-terminal domain was determined to be approximately 1-10
      microM. Thus, in normal, undamaged cells p53 may be largely monomeric.
      Enhancement of tetramer formation through phosphorylation of Ser392, coupled with
      a DNA-damage-induced increase in its nuclear concentration, could provide a
      switch that activates p53 as a transcription factor in response to DNA damage.

PMID- 9254609
TI  - Changes in the reaction mechanism of electron transfer from plastocyanin to
      photosystem I in the cyanobacterium Synechocystis sp. PCC 6803 as induced by site
      directed mutagenesis of the copper protein.
AB  - The kinetic mechanism of plastocyanin oxidation by photosystem I in the
      cyanobacterium Synechocystis sp. PCC 6803 is drastically changed by modifying the
      metalloprotein by site-directed mutagenesis. The mutations herein considered
      concern four specific residues, two in the east face and the other two in the
      hydrophobic patch of plastocyanin. The first set of mutants include D44A, D44K,
      D47A, and D47R, as well as the double mutants D44A/D47A and D44R/D47R; the second
      set consists of L12A and K33E. The kinetic efficiency of all these mutant
      plastocyanins has been analyzed by laser-flash absorption spectroscopy. The
      plastocyanin concentration dependence of the observed electron transfer rate
      constant (kobs) is linear with most mutant plastocyanins, as with wild-type
      plastocyanin, but exhibits a saturation plateau at high protein concentration
      with the double mutant D44R/D47R, which suggests the formation of a plastocyanin
      PSI transient complex. The effect of ionic strength on kobs varies from the wild
      type plastocyanin to some of the mutants, for instance D44K, for which the salt
      concentration dependence of kobs is just the reverse as compared to the wild-type
      protein. The ionic strength dependence of kobs with D44R/D47R exhibits a bell
      shaped profile, which is similar to that of green algae and higher plants. These
      findings indicate that the double mutant D44R/D47R follows a reaction mechanism
      involving not only complex formation with PSI but also further reorientation to
      properly accommodate the redox centers prior to electron transfer, as is the case
      in most evolved species, whereas the wild-type copper protein reacts with PSI by
      following a simple collisional kinetic model.

PMID- 9254610
TI  - Tyrosyl interactions in the folding and unfolding of bovine pancreatic
      ribonuclease A: a study of tyrosine-to-phenylalanine mutants.
AB  - Three tyrosine-to-phenylalanine mutants of ribonuclease A (Y25F, Y92F, and Y97F)
      are investigated for their enzymatic activities, molecular stabilities, and
      unfolding/refolding kinetics. These mutants exhibit 80, 90, and 80%,
      respectively, of the catalytic activity of the wild-type enzyme. Thermal,
      Gdn.HCl, and pH transition measurements indicate that Y25F and Y97F are less
      stable than the wild-type protein, whereas the bulk of the thermodynamic and
      kinetic evidence indicates that Y92F is as stable as the wild-type protein.
      Differences in molar extinction coefficients indicate that tyrosines 25, 92, and
      97 contribute 38, 13, and 39%, respectively, to the absorption difference between
      the folded and unfolded states, in general agreement with previous studies but
      possibly indicating the contribution of a fourth tyrosine residue to account for
      the remaining 10%. Stopped-flow single- and double-jump kinetic experiments were
      carried out on the wild-type and three mutant proteins. At least one tyrosine
      residue besides tyrosine 92 contributes to the slow fluorescence-unfolding phase;
      the likely candidate for this residue is tyrosine 115 which monitors the cis
      trans isomerization of the X-Pro114 peptide bond. Tyrosines 25 and 97 are
      involved in interactions that retard conformational unfolding and accelerate
      conformational refolding as well as the cis-trans proline isomerization of the
      slow-refolding phases, presumably by stabilizing the major beta-hairpin structure
      of RNase A. These interactions may contribute to the strong pH dependence of the
      folding and unfolding of ribonuclease A. In contrast, tyrosine 92 does not affect
      the folding and unfolding rates significantly. An improved "box" model of proline
      isomerization under unfolding conditions was derived from exhaustive fitting of
      all possible box models. The kinetic data support the identification of Pro93 as
      the proline whose isomerization distinguishes the slow-refolding species (USII
      and USI) from the other, faster-refolding species (Uvf, Uf, and Um), implying
      that Pro93 isomerizes in the slow-refolding reactions USI --> N and IN --> N.
      Similarly, Pro114 seems to distinguish between the very fast-refolding species
      Uvf and the fast-refolding species Uf. Lastly, Pro117 seems to distinguish the
      major slow-refolding species USII from the minor slow-refolding species USI and
      the medium-refolding species Um from the fast- and very fast-refolding species.

PMID- 9254611
TI  - Solution dynamics and secondary structure of murine leukemia inhibitory factor: a
      four-helix cytokine with a rigid CD loop.
AB  - Leukemia inhibitory factor (LIF) is a hematopoietic cytokine which elicits its
      effects on diverse cell types via both gp130 and a more specific LIF receptor.
      Recombinant murine LIF was studied by multidimensional homonuclear and 1H-15N
      heteronuclear NMR and 95% of backbone amide resonances assigned. Definition of
      the secondary structure by chemical shift data and NOE connectivities shows a
      four-alpha-helix bundle fold (helices A-D) in solution, with an additional
      flexible turn of helix in the AB loop. Subtle differences are seen in the
      conformations of helices A and D from those defined in the crystal structure
      [Robinson, R. C., Grey, L. M., Staunton, D., Vankelcom, H., Vernallis, A. B.,
      Moreau, J.-F., Stuart, D. I., Heath, J. K., & Jones, E. Y. (1994) Cell77, 1101
      1116]. The dynamics of the polypeptide backbone of LIF were assessed from 15N T1
      and T2 relaxation times and 15N-1H heteronuclear NOEs of the amide groups. Using
      model-free formalism, the overall rotational correlation time of LIF in solution
      is calculated to be 9.7 ps. The four alpha-helices are relatively rigid, and high
      mobility is observed for N-terminal residues (Ser 1-Asn 21) and the AB loop. In
      contrast to several closely related cytokines, the long CD loop is relatively
      rigid. This may have implications for interactions with the specific LIF
      receptor, which binds in this region.

PMID- 9254612
TI  - Effects of GTP on bound nitric oxide of soluble guanylate cyclase probed by
      resonance Raman spectroscopy.
AB  - Soluble guanylate cyclase (sGC) was isolated from bovine lung, and its resonance
      Raman (RR) spectra were investigated for the reduced, CO-bound (CO-sGC), NO-bound
      (NO-sGC), oxidized, and oxidized NO-bound forms in the presence and absence of
      GTP. The enzyme was purified by more than 12 000-fold in terms of specific
      activity than the supernatant of homogenates, and the heme content was determined
      with the pyridine hemochoromogen method and Bradford's protein assay to be 0.8
      per heterodimer (alpha, Mr = 74 000; beta, Mr = 69 000). The RR spectra of sGC
      and CO-sGC including the Fe-His stretch at 203 cm-1 and the Fe-CO stretch at 473
      cm-1 were unaltered by binding of GTP and cGMP, but apparent RR spectra of NO-sGC
      in the presence of GTP changed with time and concentrations of GTP. In the
      absence of GTP, the RR bands of the N-O stretch (nuNO) and the Fe-NO stretch
      (nuFe-NO) were observed at 1681 and 521 cm-1, respectively. In its presence,
      however, two nuNO bands were observed at 1700 and 1681 cm-1, which exhibited 15NO
      isotopic frequency shifts of 32 and 34 cm-1, respectively. Similar Raman spectral
      changes were observed with the same amount of cGMP but not with PPi or GTP
      analogues including ATP, GMPPNP, and GTPgammaS. This suggests that GTP or cGMP
      binds to the distal side of the heme in the proximity of bound NO, possibly
      regulating NO binding.

PMID- 9254613
TI  - Functionally linked hydration changes in Escherichia coli aspartate
      transcarbamylase and its catalytic subunit.
AB  - Aspartate transcarbamylase (ATCase) is a highly regulated, dodecameric enzyme
      that catalyzes the first committed step in pyrimidine biosynthesis. Upon
      ligation, ATCase undergoes a conformational transition from a low-activity T
      state to a high-activity R-state. This transition involves major changes in the
      molecular architecture, including structural rearrangements of several
      intersubunit interfaces and a 12 A expansion of the molecule along its 3-fold
      axis. Solute-induced osmotic stress experiments report that approximately 208
      solvent waters are taken up by ATCase as it binds substrate. Solvent-accessible
      surface area calculations conducted on the T and R conformers of ATCase agree
      very well with this result, predicting that approximately 189 waters are taken up
      during this conformational change. Both osmotic stress measurements and surface
      area calculations on the catalytic trimer of ATCase predict water release upon
      ligation of the trimer. Specific aspects of the application of osmotic stress to
      ATCase are also discussed, including solute size effects, and an assessment of
      potential alternative explanations for these results.

PMID- 9254614
TI  - Identification of cysteine-523 in the aspartate binding site of Escherichia coli
      asparagine synthetase B.
AB  - The site-directed chemical modifier [p-(fluorosulfonyl)benzoyl]adenosine (5'
      FSBA) inactivates Escherichia coli asparagine synthetase B activity following
      pseudo-first-order kinetics, with ATP providing specific protection, with a Kd of
      12 microM. The 5'-FSBA modification appears to be covalent, even though a
      nonstoichiometric amount (less than 10%) of radiolabeled 5'-FSBA was associated
      with a totally inactivated enzyme. However, the inactivation by 5'-FSBA could be
      reversed upon the addition of dithiothreitol. These results are indicative of 5'
      FSBA-induced disulfide bond formation, which requires the presence of at least
      two cysteine residues in the proximity of the ATP binding site. Identification of
      the critical cysteine residue was accomplished by sequential replacement of each
      cysteine in the protein by site-directed mutagenesis. Cys 523 was identified as
      the key residue involved in the formation of the 5'-FSBA-induced disulfide bond.
      Detailed kinetic analyses and comparison with similar enzymes, suggest that this
      cysteine residue, while in close proximity to the ATP binding site, is actually
      involved in aspartate binding in asparagine synthetase B.

PMID- 9254615
TI  - Kinetics of protoporphyrinogen oxidase inhibition by diphenyleneiodonium
      derivatives.
AB  - Protoporphyrinogen oxidase, the last enzyme of the common branch of the heme and
      chlorophyll pathways in plants, is the molecular target of diphenyl ether-type
      herbicides. These compounds inhibit the enzyme competitively with respect to the
      tetrapyrrole substrate, protoporphyrinogen IX. We used the flavinic nature of
      protoporphyrinogen oxidase to investigate the reactivity of the enzyme toward the
      2,2'-diphenyleneiodonium cation, a known inhibitor of several flavoproteins.
      Diphenyleneiodonium inhibited the membrane-bound yeast protoporphyrinogen oxidase
      competitively with molecular oxygen. The typical slow-binding kinetics suggested
      that the enzyme with a reduced flavin rapidly combined with the inhibitor to form
      an initial complex which then slowly isomerized to a modified enzyme-inhibitor
      complex (Ki = 6.75 x 10(-8) M, Ki* = 4.1 x 10(-9) M). This inhibition was
      strongly pH-dependent and was maximal at pH 8. Substituted diphenyleneiodoniums
      were synthesized and shown to be even better inhibitors than 2,2'
      diphenyleneiodonium: Ki = 4.4 x 10(-8) M and Ki* = 1.3 x 10(-9) M for 4-methyl
      2,2'-diphenyleneiodonium, Ki = 2.2 x 10(-8) M and Ki * = 1.1 x 10(-9) M for 6
      methyl-2,2'-diphenyleneiodonium, and Ki = 6.4 x 10(-9) M and Ki* = 1.2 x 10(-1)2
      M for 4-nitro-2,2'-diphenyleneiodonium. The 4-nitro-2,2'-diphenyleneiodonium was
      a quasi irreversible inhibitor (k5/k6 > 5000). Diphenyleneiodoniums are a new
      class of protoporphyrinogen oxidase inhibitors that act via a mechanism very
      different from that of diphenyl ether-type herbicides and appear to be promising
      tools for studies on the structure-function relationships of this agronomically
      important enzyme.

PMID- 9254617
TI  - Raman study of the polarizing forces promoting catalysis in 4-chlorobenzoate-CoA
      dehalogenase.
AB  - The enzyme 4-chlorobenzoate-CoA dehalogenase catalyzes the hydrolysis of 4
      chlorobenzoate-CoA (4-CBA-CoA) to 4-hydroxybenzoyl-CoA (4-HBA-CoA). In order to
      facilitate electrophilic catalysis, the dehalogenase utilizes a strong polarizing
      interaction between the active site residues and the benzoyl portion of the
      substrate [Taylor, K. L., et al. (1995) Biochemistry 34, 13881]. As a result of
      this interaction, the normal modes of the benzoyl moiety of the bound 4-HBA-CoA
      undergo a drastic rearrangement as shown by Raman spectroscopy. Here, we present
      Raman difference spectroscopic data on the product-enzyme complex where the
      product's benzoyl carbonyl is labeled with 18O (C=18O) or 13C (13C=O) or where
      the 4-OH group is labeled with 18O. The data demonstrate that the carbonyl group
      participates in the most intense normal modes occurring in the Raman spectrum in
      the 1520-1560 cm-1 region. The substrate analog 4-methylbenzoate-CoA (4-MeBA-CoA)
      has also been characterized by Raman difference spectroscopy in its free form and
      bound to the dehalogenase. Upon binding, the 4-MeBA-CoA shows evidence of
      polarization within the delocalized pi-electrons, but to a lesser extent compared
      to that seen for the product. The use of 4-MeBA-CoA labeled with 18O at the
      carbonyl enables us to estimate the degree of electron polarization within the
      C=O group of the bound 4-MeBA-CoA. The C=O stretching frequency occurs near 1663
      cm-1 in non-hydrogen bonding solvents such as CCl4, near 1650 cm-1 in aqueous
      solution, and near 1610 cm-1 in the active site of dehalogenase. From model
      studies, we can estimate that in the active site the carbonyl group behaves as
      though it is being polarized by hydrogen bonds approximately 57 kJ mol-1 in
      strength. Major contributions to this polarization come from hydrogen bonds from
      the peptide NHs of Gly114 and Phe64. However, an additional contribution, which
      may account for up to half of the observed shift in nuC=O, originates in the
      electrostatic field due to the alpha-helix dipole from residues 121-114. The
      helix which terminates at Gly114, near the C=O group of the bound benzoyl,
      provides a dipolar electrostatic component which contributes to the polarization
      of the C=O bond and to the polarization of the entire benzoyl moiety. The effect
      of both the helix dipole and the hydrogen bonds on the C=O is a "pull" of
      electrons onto the carbonyl oxygen, which, in turn, polarizes the electron
      distribution within the benzoyl pi-electron system. The ability of these two
      factors to polarize the electrons within the benzoyl moiety is increased by the
      environment about the benzoyl ring; it is surrounded by hydrophobic residues
      which provide a low-dielectric constant microenvironment. Electron polarization
      promotes catalysis by reducing electron density at the C4 position of the benzoyl
      ring, thereby assisting attack by the side chain of Asp145. An FTIR study on the
      model compound 4-methylbenzoyl S-ethyl thioester, binding to a number of hydrogen
      bonding donors in CCl4, is described and is used to relate the observed shift of
      the C=O stretching mode of 4-MeBA-CoA in the active site to the hydrogen bonding
      strength value. Since the shift of the C=O frequency upon binding is due to
      hydrogen bonding and helix dipole effects, we refer to this bonding strength as
      the effective hydrogen bonding strength.

PMID- 9254616
TI  - Isotope effect studies on the calcineurin phosphoryl-transfer reaction:
      transition state structure and effect of calmodulin and Mn2+.
AB  - The hydrolysis of p-nitrophenyl phosphate (pNPP) catalyzed by calcineurin has
      been studied by measurement of heavy-atom isotope effects in the substrate. The
      isotope effects were measured at the nonbridging oxygen atoms [18(V/K)nonbridge],
      at the position of bond cleavage in the bridging oxygen atom [18(V/K)bridge], and
      at the nitrogen atom in the nitrophenol leaving group [15(V/K)]. The isotope
      effects increased in magnitude upon moving from the pH optimum of 7.0 to 8.5;
      18(V/K)bridge increased from 1.0072 to 1.0115, and 15(V/K) from 1.0006 to 1.0014.
      The value for 18(V/K)nonbridge is 0.9942 at pH 8.5. These data are consistent
      with P-O bond cleavage being partially rate-limiting at the pH optimum and more
      so at the higher pH. The 18(V/K)nonbridge isotope effect indicates that the
      dianion is the substrate for catalysis, and a dissociative transition state is
      operative for phosphoryl transfer. Increasing the concentration of the activating
      metal ion Mn2+ at pH 7.0 from 1 mM to 5 mM increases the magnitude of the isotope
      effects by an amount similar to that observed with the shift in pH from 7.0 to
      8.5, indicative of a change in the commitment factor in the kinetic mechanism so
      as to make the chemical step more rate-limiting.

PMID- 9254618
TI  - The N-linked oligosaccharides of the beta-subunit of rabbit gastric H,K-ATPase:
      site localization and identification of novel structures.
AB  - The gastric H,K-ATPase is responsible for acid secretion by parietal cells. Its
      beta-subunit is a glycoprotein which is exposed to the harsh, acidic environment
      of the stomach. The location and structural features of the N-linked
      oligosaccharides were determined using matrix-assisted laser desorption
      ionization mass spectrometry (MALDI/MS) (in conjunction with mass composition
      analysis and exoglycosidase digestions), Edman degradation, and monosaccharide
      composition analysis. All seven N-linked sequons at positions 99, 103, 130, 146,
      161, 193, and 222 were fully glycosylated. An unusual restricted array of
      oligosaccharides was observed at individual Asn residues. Asn99 was modified
      exclusively with oligomannosidic-type structures (Man6GlcNAc2-Man8GlcNAc2).
      Asn193 contained both oligomannosidic (Man5GlcNAc2-Man8GlcNAc2) and lactosamine
      type structures, indicating significant "leakiness" in the pathway which converts
      oligomannose to lactosamine-type at a single glycosylation site. MALDI/MS with
      collision-induced dissociation was required to demonstrate that sequons separated
      by a single residue (99Asn-Ile-Ser-Asp-Asn-Arg-Thr105) were modified with only
      oligomannose and lactosamine structures, respectively. Analysis of the total
      oligosaccharide pool using MALDI/MS and exoglycosidase analysis revealed 24
      lactosamine species (bi-, tri-, and tetraantennary structures), with all branches
      terminated in alpha-linked Gal residues, most possessing a single Fuc residue.
      Nine novel oligosaccharides contained multiple alpha-linked Gal residues per
      branch. Bi- and triantennary structures, with and without lactosamine repeats,
      were observed at Asn146 and Asn161. Tetraantennary structures with lactosamine
      repeats were found only at Asn130, and this site also contained most of the
      structures with multiple alpha-linked Gal residues per branch.

PMID- 9254619
TI  - Transmembrane orientation of hydrophobic alpha-helices is regulated both by the
      relationship of helix length to bilayer thickness and by the cholesterol
      concentration.
AB  - A fluorescence-based approach to evaluate the regulation of transmembrane
      orientation of alpha-helices has been developed to examine the behavior of a
      membrane-inserted alpha-helical peptide with a 19 residue hydrophobic sequence.
      The emission lambdamax of a Trp residue in the helix was used to determine its
      location in the bilayer. To calibrate this method, Trp lambdamax and depth
      (determined by parallax analysis of fluorescence quenching) were measured for
      transmembrane peptides with Trp at different positions. Transmembrane orientation
      of the alpha-helix was found to be destabilized by differences between the width
      of the bilayer and the length of the hydrophobic sequence (i.e., hydrophobic
      mismatch). When bilayer width exceeded the length of the hydrophobic segment,
      mismatch induced formation of a nontransmembraneous orientation close to the
      polar/hydrocarbon interface. By manipulation of bilayer width in situ, it was
      found that the transmembrane and nontransmembrane orientations could
      interconvert. Cholesterol altered the transmembrane/nontransmembrane equilibrium
      to a degree consistent with its tendency to increase bilayer thickness.
      Evaluation of the energetics of transmembrane vs nontransmembrane insertion
      showed increased mismatch of a helix with bilayer width by the equivalent of just
      one hydrophobic residue can destabilize transmembrane orientation by roughly 0.5
      kcal/mol. Inclusion of 30 mol % cholesterol in a bilayer can alter transmembrane
      insertion stability by 3-5 kcal/mol. Thus, physiologically relevant variations in
      both the hydrophobic helix length/membrane thickness ratio and the cholesterol
      levels influence transmembrane insertion significantly.

PMID- 9254620
TI  - Heat shock protein 80 of Neurospora crassa, a cytosolic molecular chaperone of
      the eukaryotic stress 90 family, interacts directly with heat shock protein 70.
AB  - The subunit structure of Hsp80, the most abundant heat-shock protein of
      Neurospora crassa, was examined by chemical cross-linking of the purified protein
      in vitro. Resolution of glutaraldehyde-treated Hsp80 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis SDS-PAGE suggests that the native state of
      this protein is a tetramer; the relative proportion of cross-linked species,
      estimated by the fraction of protein recovered in each category, is consistent
      with a dimer-of-dimer structure. Upon interaction with nucleotides, higher order
      cross-linked oligomers were detected, indicating ligand-induced conformational
      changes. The effect of nucleotides was also monitored by following tryptophan
      fluorescence: CTP, UTP, and NAD led to fluorescence quenching, the effect of CTP
      being the most pronounced. As individual molecular chaperones often act in
      concert with cochaperones, interaction between the two major cytosolic stress
      proteins--Hsp80 and Hsp70--was examined. Purified Hsp70 was immobilized on ATP
      agarose and purified Hsp80 was applied to the Hsp70-saturated matrix; while Hsp80
      did not bind to ATP-agarose by itself, it was bound strongly by immobilized
      Hsp70. The [Hsp70-Hsp80] complex was eluted with ATP and coelution of both
      proteins was confirmed by Western blot analysis, using specific polyclonal
      antibodies raised against each protein. The physical association of stress
      inducible Hsp70 and Hsp80 was verified by interprotein cross-linking in vitro
      followed by immunoblot analysis and by immunoprecipitation.

PMID- 9254621
TI  - Guanidine hydrochloride-induced denaturation and refolding of transthyretin
      exhibits a marked hysteresis: equilibria with high kinetic barriers.
AB  - Fluorescence and circular dichroism spectroscopy as well as analytical
      ultracentrifugation and glutaraldehyde cross-linking were utilized to evaluate
      the tertiary and quaternary structural changes occurring on the denaturation and
      reconstitution pathways of transthyretin (TTR) as a function of guanidine
      hydrochloride (GdnHCl) concentration. These results demonstrate that the GdnHCl
      mediated denaturation and reconstitution of TTR is reversible. However, the
      lowest GdnHCl concentration that dissociates and unfolds transthyretin does not
      allow the unfolded monomer to refold to tetramer at a rate that is measurable. As
      a result, there is a striking hysteresis observed upon comparison of the GdnHCl
      mediated denaturation and reconstitution transitions. The TTR tetramer does not
      dissociate into unfolded monomer until the denaturant concentration exceeds 4 M
      GdnHCl, whereas unfolded monomeric TTR (denatured in 7 M GdnHCl) does not refold
      and assemble into a native tetrameric structure until the GdnHCl concentration is
      reduced to less than 2 M. These results imply that a significant kinetic barrier
      intervenes between the folded tetramer and unfolded monomer in both the
      denaturation and reconstitution directions at pH 7. A kinetics study of the
      denaturation of TTR as a function of GdnHCl concentration yields a first-order
      rate constant for unfolding of (9.0 +/- 7.5) x 10(-11) s-1, estimated by
      extrapolation of the rate constants for the tetramer to unfolded monomer
      transition as a function of GdnHCl to 0 M GdnHCl. This rate is very slow; as a
      result, wild-type TTR is predicted to be kinetically stable as a tetrameric
      quaternary structure once formed. These results imply that the rate of TTR
      dissociation and partial unfolding to the monomeric amyloidogenic intermediate
      under denaturing conditions may play a role in transthyretin-based amyloid
      diseases.

PMID- 9254622
TI  - Sequential metal binding by the RING finger domain of BRCA1.
AB  - Analysis of the amino acid sequence encoded by the familial breast and ovarian
      cancer susceptibility gene, BRCA1 [Miki et al. (1994) Science 266, 66-71],
      revealed the presence of an amino-terminal RING finger domain, a zinc binding
      motif found in a variety of proteins. Previously determined structures of two
      RING finger peptides from other proteins revealed that each RING finger sequence
      forms a single domain that includes two interleaved metal binding sites. One is a
      four-cysteine site comprised of metal binding residues 1, 2, 5, and 6 (in terms
      of position along the amino acid sequence) (site 1) and the other is a three
      cysteine, one-histidine site involving metal binding residues 3, 4, 7, and 8
      (site 2). We have characterized the metal binding and metal-dependent folding
      properties of peptides encompassing the BRCA1 RING finger. Using cobalt(II) as a
      spectroscopic probe, we have found that metal binding is sequential, with site 1
      becoming nearly fully occupied prior to metal binding to site 2. More detailed
      thermodynamic analysis as well as studies of a variant peptide revealed that
      metal binding appears to be anticooperative with dissociation constants of 3 x
      10(-8) M for site 1, 5 x 10(-7) M for site 2 with site 1 unoccupied, and 8 x 10(
      6) M for site 2 when site 1 is occupied. Circular dichroism spectroscopic studies
      revealed that the BRCA1 RING finger peptide is somewhat structured at pH 7 in the
      absence of metal ions, with further structural changes occurring after the metal
      binding.

PMID- 9254623
TI  - Solution conformation of a five-nucleotide RNA bulge loop from a group I intron.
AB  - We present the solution conformation, determined by NMR spectroscopy, of a five
      nucleotide RNA bulge loop. The bulge interrupts the stem of a 25-nucleotide RNA
      hairpin, and its sequence and flanking sequences are those of a conserved bulge
      from a Group I intron. The secondary structure of the bulge loop in the hairpin
      context is that predicted by the secondary structure prediction algorithm of
      Zuker. It differs, however, from the secondary structure deduced from sequence
      covariation of the bulge in the context of the functionally folded Group I
      introns and observed in the crystal structure of an independently folding domain
      of the Group I intron from Tetrahymena thermophila. This difference represents an
      exception to the heierarchical model of RNA folding in which preformed elements
      of secondary structure interact to form a tertiary structure. The three
      dimensional structure of the bulge loop is characterized by discontinuous base
      stacking. Adjacent adenines stack with each other and with the flanking double
      helices. However, the position of the central uracil is not well defined by NOE
      distance constraints and is a point of discontinuity in the base stacking.

PMID- 9254625
TI  - Dynamics of carbon monoxide binding with cytochromes P-450.
AB  - The dynamics of CO rebinding with cytochromes P-450cam, P-450scc, and P-450LM2
      after laser flash photolysis have been investigated from 293 to 77 K, and the
      distribution functions of the rate parameters P(k) and of the activation enthalpy
      P(H) were determined using the maximum entropy method. In a fluid solvent,
      geminate rebinding is nonexponential, presumably because of a spectral shift
      induced by protein relaxation on the same time scale. Substrate binding increases
      the yield of the bimolecular process and decreases the bimolecular rate by 1 or 2
      orders of magnitude. The amplitude of these effects seems to correlate with
      substrate specificity. In a rigid environment at low temperature, cytochromes P
      450 exhibit a bimodal distribution of activation enthalpy; P(H) consists of two
      distinct bands which are in a thermal equilibrium even at 77 K. The results lead
      to a scheme in which a common structural perturbation splits the conformational
      substates of cytochromes P-450 into pairs of "doublet" substates with different
      dynamic properties. The hierarchy of conformational substates of cytochromes P
      450 thus contrasts with that of oxygen-binding hemoproteins such as myoglobin.

PMID- 9254624
TI  - The major, N2-dG adduct of (+)-anti-B[a]PDE shows a dramatically different
      mutagenic specificity (predominantly, G --> A) in a 5'-CGT-3' sequence context.
AB  - Mutations induced by the (+)-anti diol epoxide of benzo[a]pyrene [(+)-anti
      B[a]PDE] were described previously in the supF gene of the Escherichia coli
      plasmid pUB3 [Rodriguez et al.(1993) Biochemistry, 32, 1759]. (+)-anti-B[a]PDE
      induced a complex pattern of mutations, including insertions, deletions,
      frameshifts, as well as base substitution mutations, which for G:C base pairs
      alone included a significant fraction of G:C --> T:A, A:T and C:G mutations. A
      variety of results suggest that most of these mutations arise from the major
      adduct ([+ta]-B[a]P-N2-dG), raising the question how can a single adduct induce
      different kinds of mutations? Our working hypothesis in this regard is that (1)
      an adduct can adopt multiple conformations; (2) different conformations cause
      different mutations; and (3) adduct conformation is controlled by various
      factors, such as DNA sequence context. To investigate what conformation is
      associated with what mutation, it is essential to find examples where [+ta]-B[a]P
      N2-dG induces principally one kind of mutation as a prelude to the study in that
      same context of the conformation(s) potentially relevant to mutagenesis. Earlier
      work indicated that (+)-anti-B[a]PDE gave a preponderance of G --> A mutations in
      a 5'-CGT-3 sequence context, and herein it is shown that these mutations are
      likely to be attributable to the major adduct, since in this same sequence
      context [+ta]-B[a]P-N2-dG studied site specifically also induces principally G -
      > A mutations ( approximately 82%). Previously, [+ta]-B[a]P-N2-dG was shown to
      induce principally G --> T mutations (approximately 97%) in a 5'-TGC-3' sequence
      context. Thus, by simply altering its surrounding sequence context this adduct
      can give a preponderance of either G --> A or G --> T mutations. This is the most
      dramatic change in base substitution mutagenic specificity for an adduct
      described to date and illustrates that the qualitative pattern of mutagenesis by
      a bulky adduct can be remarkably diverse.

PMID- 9254626
TI  - Partial volumes and compressibilities of extended polypeptide chains in aqueous
      solution: additivity scheme and implication of protein unfolding at normal and
      high pressure.
AB  - An empirical additivity method for calculation of the partial volumes and
      adiabatic compressibilities of extended oligo- and polypeptides having arbitrary
      amino acid compositions has been developed and tested by comparison with
      available experimental data. Its accuracy is the best among the known empirical
      approaches. Comparison of experimental data on protein denaturation with the
      results of calculation allows one to discriminate between the unfolded and molten
      globule states of globular proteins and to estimate the extent of unfolding. For
      the first time, experimental nonlinear data for the volume-pressure relationship
      in proteins and model compounds have been used to interpret the high-pressure
      denaturation of proteins. It has been shown that the two denatured states, molten
      globule and unfolded ones, can be attained by a pressure rise: the molten globule
      state by moderate pressure and the unfolded one by high pressure. The
      relationship between volumetric properties and hydration is briefly discussed.

PMID- 9254627
TI  - Isolation and conformational analysis of fragment peptide corresponding to the
      heparin-binding site of hepatocyte growth factor.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes. The mitogenic
      activity of HGF is mediated by its binding to a high-affinity receptor, c-Met.
      Heparan sulfate is an initial binding site for HGF, based on its relative
      abundance on the cell surface. The binding of HGF to heparin or heparin-like
      molecules may induce oligomerization of HGF and facilitate c-Met-dependent
      mitogenesis [Zioncheck et al. (1995) J. Biol.Chem. 270, 16871-16878]. Thus,
      heparin binding is important for the biological activity of HGF. To identify the
      heparin-binding site of HGF, we isolated fragment peptides corresponding to the
      site by limited proteolysis and chemical degradation of recombinant human HGF
      (rhHGF). The heparin-binding ability of the peptides was expressed as their
      elution positions on heparin-affinity column chromatography with NaCl gradient
      elution. Because all of the heparin-binding peptides obtained in this study were
      isolated from the N-terminal hairpin-loop region (PyrGlu32-Asn127) of HGF, the
      region was identified as the heparin-binding site of HGF. One of the isolated
      peptides, Phe42-Glu111, containing the N-terminal hairpin-loop structure, was
      considered a suitable model peptide for the heparin-binding site of HGF. From the
      observation using circular dichroism spectroscopy, it was indicated that the
      secondary structure of the peptide changed from a random structure to a beta
      sheet-like structure upon heparin binding. In addition, oligomerization of HGF in
      the presence of heparin was observed by dynamic light scattering. Based on our
      evidence, it is considered that the conformational change in the heparin-binding
      site may induce the oligomerization of HGF.

PMID- 9254628
TI  - Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus
      resistance to nucleoside inhibitors zidovudine and 3-TC.
AB  - Two mutants of HIV-1 reverse transcriptase (RT) associated with high-level
      resistance of the virus to AZT (RT-AZT: D67N, K70R, T215Y, K219Q, and M41L) or 3
      TC (RT-3TC: M184V) were expressed in Escherichia coli and purified. None of these
      mutants showed significant changes in the affinity and kinetics of binding to a
      DNA/DNA primer/template. RT-AZT was investigated in detail with respect to its
      kinetics of incorporation of nucleotides. No change in the relative rates of TMP
      and AZTMP incorporation could be detected for RT-AZT with respect to wild type
      RT. These results imply that there is no increased discrimination against AZTTP
      in the mutant. This was found for DNA/DNA and DNA/RNA primer/template.
      Additionally, rapid kinetics of incorporation of 3'-amino-3'-deoxythymidine 5'
      monophosphate (a possible metabolite of AZT) were investigated and compared with
      TMP incorporation, but no difference in its relative rates of incorporation
      between wild type RT and RT-AZT was detected. In contrast, the already very slow
      rate of incorporation of 3-TCMP seen with wild type enzyme was drastically
      reduced (by a factor of 23 and 36 with DNA/DNA primer/template and DNA/RNA
      primer/template, respectively) for RT-3TC, showing a clear correlation between in
      vitro and in vivo effects. The affinity of 3-TCTP to the RT-3TC-primer/template
      complex was not affected by the mutation M184V. A 1.6-fold cross-resistance to
      ddATP, the converted form of the prodrug ddI, could also be shown for RT-3TC, but
      no cross-resistance to ddCTP was detected. Additionally, rapid kinetics of AZTMP
      incorporation by RT-3TC were investigated. There was an indication of a slightly
      higher rate of incorporation of AZTMP by RT-3TC than wild type RT.

PMID- 9254629
TI  - Mechanisms of action of the bactericidal/permeability-increasing protein BPI on
      endotoxin and phospholipid monolayers and aggregates.
AB  - We have investigated the mechanisms of interaction of the recombinant N-terminal
      portion of bactericidal/permeability-increasing protein, rBPI21, with
      lipopolysaccharide (LPS) isolated from enterobacterial deep rough mutant strains.
      Experimentally, the ability of rBPI21 to form monolayers at the air/water
      interface and its action on lipid monolayers were analyzed. We have further
      studied the interaction of rBPI21 with aggregates from phospholipids and Re
      mutant LPS by infrared and resonance energy transfer spectroscopy and laser
      Doppler velocimetry. From monolayer experiments, the molecular area of a single
      rBPI21 molecule was estimated to be about 12 nm2. At lateral pressures of </=25
      mN/m, rBPI21 incorporated into monolayers from negatively charged LPS and
      phosphatidylglycerol (PG) but not into those from neutral phosphatidylcholine.
      rBPI21 incorporated not only into monolayers but also into liposomes made from or
      containing negatively charged phospholipids, reducing the absolute value of the
      zeta-potential of LPS and PG aggregates. Furthermore, due to intercalation,
      rBPI21 caused the rigidification of the acyl chains of lipids in the gel as well
      as in the fluid phase and significantly immobilized their phosphate groups. High
      concentrations of Mg2+ ions were found to have a protective effect against the
      action of rBPI21. On the basis of these results, the biophysical characteristics
      of rBPI21 are discussed and a model is proposed as to how the rBPI21-induced
      influence on lipid monolayers and bilayers could explain rBPI21-mediated effects
      on the bacterial membrane.

PMID- 9254630
TI  - Mechanisms of action of bactericidal/permeability-increasing protein BPI on
      reconstituted outer membranes of gram-negative bacteria.
AB  - The mechanisms of interaction of the recombinant N-terminal portion of
      bactericidal/permeability-increasing protein, rBPI21, with various planar
      asymmetric and symmetric bilayer membranes, including the lipid matrix of the
      outer membrane of Gram-negative bacteria, were investigated via electrical
      measurements. For the lipopolysaccharide (LPS) leaflet of the outer membrane,
      isolated deep rough mutant LPS of Escherichia coli strain F515 (F515 LPS) and
      Proteus mirabilis strain R45 (R45 LPS) were used. The addition of rBPI21 to the
      LPS side of asymmetric LPS/phospholipid membranes, as well as to black lipid
      membranes made from dioleoylphosphatidylglycerol (DOPG), led to membrane rupture.
      The innermembrane potential difference resulted in a slight increase from 0 to 5
      mV for symmetric DOPG membranes but changed for asymmetric F515 LPS/PL membranes
      from -36 to +8 mV and for R45 LPS/PL membranes from -37 to -5 mV following the
      addition of rBPI21. In all cases, the addition of rBPI21 led to an increase in
      membrane current. The effect of rBPI21 on the innermembrane potential difference
      of LPS/PL membranes was significantly reduced in the presence of 40 mM MgCl2
      (shift from -36 to -31 mV for F515 LPS). On the basis of these results and from
      our studies on the interaction of rBPI21 with lipid monolayers and aggregates
      [Wiese, A., et al. (1997) Biochemistry 36, 10301-10310], a model is discussed
      explaining how the observed membrane rupture, increase of membrane current, and
      change of transmembrane potential as induced by rBPI21 may contribute to
      bacterial dysfunction.

PMID- 9254631
TI  - Strand specificity in the interactions of Escherichia coli primary replicative
      helicase DnaB protein with a replication fork.
AB  - The interactions of the Escherichia coli primary replicative helicase DnaB
      protein, with synthetic DNA replication fork substrates, having either a single
      arm or both arms, have been studied using the thermodynamically rigorous
      fluorescence titration techniques. This approach allows us to obtain absolute
      stoichiometries of the formed complexes and interaction parameters without any
      assumptions about the relationship between the observed signal (fluorescence) and
      the degree of binding. Subsequently, the formation of the complexes, with
      different replication fork substrates, has also been characterized using the
      sedimentation velocity technique. To our knowledge, this is the first
      quantitative characterization of interactions of a hexameric helicase with
      replication fork substrates. In the presence of the ATP nonhydrolyzable analog,
      AMP-PNP, the E. coli DnaB helicase preferentially binds to the 5' arm of the
      single-arm fork substrate with an intrinsic affinity 6-fold higher than its
      affinity for the 3' arm. ATP hydrolysis is not necessary for formation of the
      helicase-fork complex. The asymmetric interactions are consistent with the 5' -->
      3' directionality of the helicase activity of the DnaB protein and most probably
      reflects a preferential 5' --> 3' polarity in the helicase binding to ssDNA, with
      respect to the ssDNA backbone. The double-stranded part of the fork contributes
      little to the free energy of binding. The data indicate a rather passive role of
      the duplex part of the fork in the binding of the helicase. This role seems to be
      limited to impose steric hindrance in the formation of nonproductive complexes of
      the enzyme with the fork. Quantitative analysis of binding of the helicase to the
      two-arm fork substrate shows that two DnaB hexamers can bind to the fork, with
      each single hexamer associated with a single arm of the fork. In this complex,
      the intrinsic affinity of the DnaB hexamer for the 5' arm in a two-arm fork is
      not affected by the presence of the 3' arm. Moreover, the results show that the
      3' arm is in a conformation which makes it easily available for the binding of
      the next DnaB hexamer. Because of the large size of the DnaB hexamer, the data
      indicate that the 3' arm is separated from the 5' arm. The separation of both
      arms must be to such an extent that the 3' arm can bind an additional large DnaB
      hexamer. These results reveal that the 3' arm is not engaged in thermodynamically
      stable interactions with the helicase hexamer, when it is bound in its stationary
      complex to the 5' arm of the fork. The significance of the these results for a
      mechanistic model of the hexameric DnaB helicase action is discussed.

PMID- 9254632
TI  - The conformational properties of elongation factor G and the mechanism of
      translocation.
AB  - The elongation phase of protein synthesis is promoted by two G proteins,
      elongation factor Tu (EF-Tu), which delivers aminoacyl tRNAs to the ribosome, and
      elongation factor G (EF-G), which catalyzes translocation. Crystallographic
      investigations have revealed that EF-G.GDP resembles the EF-Tu.GTP.(aminoacyl
      tRNA) complex, and it has been proposed that the translocase function of EF-G is
      derived from this similarity [Nissen, P., et al. (1995) Science 270, 1464].
      However, its significance is uncertain because the affinity of EF-G.GDP for the
      ribosome is much lower than that of the ternary complex it resembles and because
      EF-Tu.GDP, the form of EF-Tu that has low ribosome affinity, has a conformation
      radically different from that of EF-Tu.GTP or EF-Tu in the ternary complex. The
      small-angle X-ray scattering study described here was undertaken to ascertain if
      the form of EF-G that has high ribosome affinity, EF-G.GTP, the structure of
      which is unknown, could be a mimic of EF-Tu.GDP. The data show that nucleotide
      free EF-G, EF-G.GDP, EF-G. GTP, and EF-G.GMPPCP cannot be distinguished by
      solution scattering and that it is likely they all resemble crystalline EF-G.GDP.
      Since an EF-Tu-like change would easily have been detected, it follows that it
      does not occur in EF-G. These observations have significant implications for the
      mechanism of translocation.

PMID- 9254633
TI  - Tetrameric stoichiometry of a prokaryotic K+ channel.
AB  - Genes with sequences reminiscent of neuronal K+ channels have recently been
      identified in prokaryotes. These putative K+ channels appear to be integral
      membrane proteins, with multiple transmembrane sequences identified by
      hydrophobicity analysis and a sequence strikingly similar to the pore-lining "P
      region" motif found in all known eukaryotic K+ channels. This study examines the
      oligomeric state and stability in detergent micelles of SliK, a K+ channel
      homologue from Streptomyces lividans. A synthetic gene for SliK was expressed at
      high levels in Escherichia coli, and the protein was purified. The predominant
      form of the protein runs in SDS-PAGE gels as an oligomer of the 19-kDa
      polypeptide, but harsh treatments such as heat or high pH convert this slowly
      migrating material into monomeric form. A "mass-tagging" strategy developed to
      examine subunit stoichiometry shows that SliK is a homotetramer in SDS and
      dodecyl maltoside micelles. The tetrameric structure can be disrupted by P-region
      mutations known to prevent the functional expression of neuronal K+ channels. The
      tetramer is remarkably stable, showing no conversion to the monomeric form after
      14 days at room temperature. Although SliK-mediated cation flux activity was not
      observed, the tetrameric behavior of the protein argues that SliK may provide a
      system for a direct attack on the structure of a K+ channel P-region sequence.

PMID- 9254634
TI  - Structural dynamics of the Streptomyces lividans K+ channel (SKC1): oligomeric
      stoichiometry and stability.
AB  - SKC1, a 160-residue potassium channel with two putative transmembrane (TM)
      segments was recently identified from Streptomyces lividans. Its high levels of
      expression, small size, and ease of purification make SKC1 an ideal candidate for
      high-resolution structural studies. We have initiated the structural
      characterization of this channel by assessing its oligomeric behavior, stability
      in detergent, general hydrodynamic properties, and preliminary secondary
      structure content. SKC1 was readily expressed and purified to homogeneity by
      sequential metal-chelate and gel filtration chromatography. Standard SDS-PAGE,
      together with chemical cross-linking analysis indicated that SKC1 behaves as a
      tightly associated tetramer even in the presence of SDS. Using a gel shift assay
      to assess its oligomeric state, we determined that SKC1 is stable as a tetramer
      in most detergents and can be maintained in nonionic detergent solutions for
      extended periods of time. The tetramer is also stable at relatively high
      temperatures, with an oligomer-to-monomer transition occurring at approximately
      65 degrees C. The Stokes radius of the micellar complex is 5 nm as determined
      from gel filtration chromatography of SKC1 in dodecyl maltoside. Preliminary
      estimations of secondary structure from CD spectroscopy showed that the channel
      exists mostly in alpha-helical conformation, with more than 50% alpha-helical,
      close to 20% beta-sheet, 10% beta-turn, and about 15% unassigned or random coil.
      These results are consistent with the idea that a bundle of alpha-helices forming
      a tetramer around the ion-conductive pathway is the common structural motif for
      members of the voltage-dependent channel superfamily.

PMID- 9254635
TI  - Challenges in measuring patient outcomes.
AB  - Reliable and valid measurement of outcomes is a key criterion for assessing the
      efficacy and effectiveness of nursing interventions. However, measurement in
      outcomes studies present a special challenge due to the longitudinal nature of
      such studies as well as the need to operationalize the intervention, specify and
      select the most relevant contextual and outcome variables, and delineate the
      influence of other providers on outcomes. This article specifies measurement
      related issues and problems that threaten the credibility of outcome studies.
      Client-related and instrument-related measurement issues which could compromise
      outcomes measurement are also addressed.

PMID- 9254636
TI  - Whose outcomes. Patients, providers, or payers?
AB  - While it is clear that measuring outcomes is important, choosing which outcomes
      to measure remains unclear. Controversy exists in outcomes measurement as to
      which specific outcome measures should be selected. Additionally, should one set
      of outcome measures be used for one purpose, such as comparing overall medical
      outcomes and another set used for another purpose, such as comparing individual
      patient outcomes? While it becomes obvious that comparisons would be easier if
      the same outcomes were used, knowing which outcomes to choose to best measure an
      effect is not always an easy task. The challenge in outcomes measurement comes in
      selecting outcomes that are comprehensive, comparable, meaningful, and accurate
      in their reflection of the effects of care.

PMID- 9254637
TI  - The role of the Agency for Health Care Policy and Research (AHCPR) in improving
      outcomes of care.
AB  - This article describes the various outcomes programs supported by the Agency for
      Health Care Policy and Research (AHCPR). The mission of the agency is to generate
      and disseminate information that improves the delivery and quality of health
      care. The agency is charged with helping consumers, providers, purchasers, health
      plans, and policy makers meet the challenge of improving the quality of health
      care services while reducing spending. AHCPR has been recognized as funding the
      development of "gold standard" clinical practice guidelines and the source of
      unbiased, science-based information on what works and does not work in health
      care.

PMID- 9254638
TI  - The benefits of continuous performance measurement.
AB  - Performance measurement is fast becoming a way of life for health care providers
      in this age of increased accountability and outcomes reporting. Health care
      organizations are well advised to carefully select measures and measurement tools
      to adequately meet the demands of others in a cost-effective and beneficial
      manner. A strategic plan and implementation of an effective performance
      measurement system will help to guide an organization to evaluate key processes
      and implement changes to improve patient care. In February 1997, the Joint
      Commission announced new accreditation requirements for hospital and long-term
      care organizations; these organizations must enroll in an acceptable performance
      measurement system by the end of 1997 and prepare to submit data to the Joint
      Commission for at least two clinical measures within the first quarter of 1999.

PMID- 9254639
TI  - Case study. Outcomes management in orthopaedics.
AB  - Improving outcomes while maintaining quality and satisfaction in today's
      healthcare environment is a challenge. This article shares some of the foundation
      work and the results of an interdisciplinary team effort toward that goal.
      Changes in care practices and their impact on outcomes can promote the welfare of
      the patient, institution, and the nation's health.

PMID- 9254641
TI  - Nurses at the bedside. Influencing outcomes.
AB  - Nurses who provide direct care to patients significantly impact patient and
      institutional outcomes. Patient outcomes influenced by nursing interventions and
      actions include clinical, social, satisfaction, and knowledge outcomes.
      Institutional outcomes influenced by nursing interventions include quality,
      image, and financial outcomes. Although research is needed to demonstrate the
      relationship between direct nursing interventions and outcomes, it is clear that
      bedside nurses make important contributions.

PMID- 9254640
TI  - Nurse managed prenatal programs affect outcomes for corporations.
AB  - Faced with higher medical costs and increased insurance premiums, corporations
      are focusing on health promotion and wellness. With increasing numbers of women
      in the workforce, corporations have identified the need for prenatal programs. By
      developing, initiating, and evaluating outcome-based prenatal programs nurses can
      target the health care needs of this select population. One such program
      documented several outcomes including improved employee health and an 86%
      reduction in maternal/newborn costs.

PMID- 9254642
TI  - Outcomes research. Clues to quality and organizational effectiveness?
AB  - Outcomes research has often been touted as the best response to concerns about
      quality in today's health care organizations. Yet, outcomes research is
      accompanied by its own set of problems. These problems must be addressed if
      outcomes research is, in fact, to guide assessments of quality and of
      organizational effectiveness. One question is how quality and organizational
      effectiveness should be defined. In addition, measurement issues are particularly
      problematic in outcomes research, as is the availability of appropriate data.
      This article discusses each of these areas, and concludes by presenting an
      integrated model to guide the assessment of outcomes, quality, and organizational
      effectiveness.

PMID- 9254644
TI  - A focused strategic plan for outcomes evaluation.
AB  - This article describes how organizations devise strategic directions. The process
      of focused strategic or hoshin planning is introduced and reviewed. This model
      illustrates how a nursing department planned a focused strategic direction for
      outcomes evaluation. This discussion includes the dedication of resources, the
      focusing of research priorities and a summary of the outcomes evaluation program,
      and the method used for implementation of the priorities. Finally, benefits of
      both the focused planning process and the outcomes evaluation program are
      discussed.

PMID- 9254643
TI  - Achieving outcomes through organizational redesign.
AB  - The current health care environment demands delivery of high quality health
      services within increasingly restricted cost parameters. To meet these demands
      health care organizations are seeking performance improvement at every level
      within the organization. Delivering care is the core business of health care
      organizations. It is a complex process composed of multiple, interfacing
      processes and subprocesses. Successful redesign does not seek to make incremental
      improvement, but to create a new organizational framework in which processes
      enable achievement of quality, service, and cost outcomes. This article examines
      drivers for redesign, presents a process for redesigning health care
      organizations, describes successful management of organizational change, and
      presents a case study of a successful redesign initiative.

PMID- 9254645
TI  - Endometriosis: a review on its pathogenesis.
AB  - Although peritoneal endometriosis was recognized in 1860, its pathogenesis still
      remains unclear. Several theories attempt to explain the pathogenesis of this
      condition. From these, the implantation theory maintains that peritoneal
      endometriosis is the result of implantation and subsequent growth of retrogradely
      shed viable endometrial cells. Based on a second theory, the peritoneal
      mesothelium transforms to an endometrium-like tissue under the influence of
      products of regurgitated endometrium (induction). Cell adhesion molecules could
      be functionally involved in the binding of the endometrial cells to the
      peritoneal lining. In peritoneal endometriosis, a delicate equilibrium seems to
      exist between attacking forces (retrograde menstruation) and the defense
      mechanisms. On one hand, the amount and the nature of the regurgitated menstrual
      debris seems important to the development of the disease. On the other hand, the
      active intra-abdominal milieu may be involved. This milieu probably converts the
      regurgitated endometrial tissue into single cells via loss of functional cell
      adhesion properties. Endometriosis may result form the impairment of the function
      of the peritoneal milieu in disposing of the regurgitated cells. Alternatively,
      the endometriosis may occur if the number of regurgitated cells is too large. An
      intact peritoneal lining may be an important additional line of defense in
      preventing the binding of the endometrial cells. Endometriosis is likely to
      develop if such defense mechanisms fail. Here, the scientific basis of the
      endometriosis theories is discussed.

PMID- 9254646
TI  - Introduction of a glycosylation site into a secreted protein provides evidence
      for an alternative antigen processing pathway: transport of precursors of major
      histocompatibility complex class I-restricted peptides from the endoplasmic
      reticulum to the cytosol.
AB  - We found that the presentation of a H-2Kd-restricted determinant from influenza
      virus nucleoprotein (NP) to T cells is strictly dependent on expression of the
      transporter associated with antigen presentation (TAP), regardless of whether NP
      is expressed as a cytosolic or secreted NP (SNP). Introducing an N-linked
      glycosylation site into the determinant selectively reduced presentation of SNP.
      This indicates that glycosylation does not interfere with TAP-transported
      peptides, and therefore that cytosolic peptides derived from SNP must have been
      exposed to the glycosylation machinery of the endoplasmic reticulum (ER) before
      their existence in the cytosol. Based on these findings, we propose that TAP
      dependent processing of at least some ER-targeted proteins entails the
      reimportation of protein from the secretory pathway to the cytosol, where the
      protein is processed via the classical pathway.

PMID- 9254647
TI  - Estrogen inhibits bone resorption by directly inducing apoptosis of the bone
      resorbing osteoclasts.
AB  - Estrogen deficiency causes bone loss, which can be prevented by estrogen
      replacement therapy. Using a recently developed technique for isolation of highly
      purified mammalian osteoclasts, we showed that 17 beta-estradiol (E2) was able to
      directly inhibit osteoclastic bone resorption. At concentrations effective for
      inhibiting bone resorption, E2 also directly induced osteoclast apoptosis in a
      dose- and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial
      antagonists, respectively, completely or partially blocked the effect of E2 on
      both inhibition of osteoclastic bone resorption and induction of osteoclast
      apoptosis. These data suggest that the protective effects of estrogen against
      postmenopausal osteoporosis are mediated in part by the direct induction of
      apoptosis of the bone-resorbing osteoclasts by an estrogen receptor- mediated
      mechanism.

PMID- 9254648
TI  - Role of the thymus in transplantation tolerance in miniature swine. I.
      Requirement of the thymus for rapid and stable induction of tolerance to class I
      mismatched renal allografts.
AB  - The almost uniform failure in transplant patients of tolerance-inducing regimens
      that have been found to be effective in rodents, has made it necessary to examine
      large animal models before testing of new approaches clinically. Miniature swine
      have been shown to share many relevant immunologic parameters with humans, and
      because of their reproducible genetics, have proved extremely useful in providing
      such a large animal model. We have previously shown that indefinite systemic
      tolerance to renal allografts in miniature swine is induced in 100% of cases
      across a two-haplotype class I plus minor histocompatibility antigen disparity by
      a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection
      observed uniformly without CyA treatment. In the present study, we have examined
      the role of the thymus during the induction of tolerance by performing a complete
      thymectomy 21 d before renal transplantation. This analysis demonstrated a
      striking difference between thymectomized and nonthymectomized animals.
      Thymectomized swine developed acute cellular rejection characterized by a T cell
      (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor
      CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a
      mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in
      vitro. These results indicate that the thymus is required for rapid and stable
      induction of tolerance.

PMID- 9254649
TI  - Tolerance induction and autoimmune encephalomyelitis amelioration after
      administration of myelin basic protein-derived peptide.
AB  - Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the
      central nervous system, is an animal model of paralyzing human disease, multiple
      sclerosis. EAE is readily induced by immunization with myelin basic protein (MBP)
      in mice transgenic for an alphabeta T cell receptor (TCR) that is specific for
      MBP. Subcutaneous injection of p17 (a peptide consisting of 17 NH2-terminal
      aminoacids of MBP) in complete Freund's adjuvant (CFA) causes paralysis.
      Induction of paralysis is inhibited by prior intraperitoneal injection of the
      same peptide in incomplete Freund's adjuvant (IFA). In addition, ongoing
      paralysis is ameliorated by subsequent intraperitoneal injection of p17 in IFA.
      Tolerance induction is equally efficient in Fas-deficient and IL-4-deficient TCR
      transgenic mice, suggesting that neither activation-induced cell death nor
      differentiation into Th2 type cells plays a role in the tolerance induction.
      Tolerance induction by p17 seems to be based on reduction in the responsiveness
      of anti-MBP T cells, as documented by lower overall antigen-induced lymphokine
      production and proliferation, as well as diminished upregulation of early
      activation marker CD69 by tolerized T cells. We propose that continuous
      encounters of MBP-specific T cells with p17 play a critical role in the induction
      and maintenance of tolerance.

PMID- 9254650
TI  - Endothelial-dependent mechanisms regulate leukocyte transmigration: a process
      involving the proteasome and disruption of the vascular endothelial-cadherin
      complex at endothelial cell-to-cell junctions.
AB  - Although several adhesion molecules expressed on leukocytes (beta1 and beta2
      integrins, platelet endothelial cell adhesion molecule 1 [PECAM-1], and CD47) and
      on endothelium (intercellular adhesion molecule 1, PECAM-1) have been implicated
      in leukocyte transendothelial migration, less is known about the role of
      endothelial lateral junctions during this process. We have shown previously
      (Read, M.A., A.S. Neish, F.W. Luscinskas, V.J. Palambella, T. Maniatis, and T.
      Collins. 1995. Immunity. 2:493-506) that inhibitors of the proteasome reduce
      lymphocyte and neutrophil adhesion and transmigration across TNF-alpha-activated
      human umbilical vein endothelial cell (EC) monolayers in an in vitro flow model.
      The current study examined EC lateral junction proteins, principally the vascular
      endothelial (VE)-cadherin complex and the effects of proteasome inhibitors (MG132
      and lactacystin) on lateral junctions during leukocyte adhesion, to gain a better
      understanding of the role of EC junctions in leukocyte transmigration. Both
      biochemical and indirect immunofluorescence analyses of the adherens junction
      zone of EC monolayers revealed that neutrophil adhesion, not transmigration,
      induced disruption of the VE-cadherin complex and loss of its lateral junction
      localization. In contrast, PECAM-1, which is located at lateral junctions and is
      implicated in neutrophil transmigration, was not altered. These findings identify
      new and interrelated endothelial-dependent mechanisms for leukocyte
      transmigration that involve alterations in lateral junction structure and a
      proteasome-dependent event(s).

PMID- 9254651
TI  - Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a
      stem cell gene.
AB  - We evaluated in vivo interactions between extrinsic (growth factor induced) and
      intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem
      cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle
      kinetics were assessed in eight strains of inbred mice using the cobblestone area
      forming cell (CAFC) assay. A strong inverse correlation was observed between
      mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in
      the femur. The population size of primitive stem cells (CAFC day 35) varied
      widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling
      and quiescent), which were similar. Administration of the early acting cytokine
      flt-3 ligand to these strains resulted in activation of quiescent primitive stem
      cells exclusively in strains with high endogenous stem cell numbers (DBA and
      AKR), but was unrelated to strain-specific progenitor cell cycling. To map loci
      affecting stem cell frequency, we quantified stem cells in BXD recombinant inbred
      mice (offspring of C57BL/6 and DBA/2). The resulting strain distribution pattern
      showed high concordance with a marker that mapped to chromosome 18 (19 cM).
      Linkage with this genomic interval was associated with a likelihood of odds score
      of 3.3, surpassing the level required for significance. Interestingly, this
      segment, containing the EGR-1 gene, shows synteny with human chromosome 5q, a
      region strongly associated with various hematological malignancies. Our findings
      indicate that a gene mapping to this region is mutated in either C57BL/6 or DBA/2
      (and possibly AKR) mice. These studies in apparently healthy mice may facilitate
      the identification of a gene implicated in human 5q-syndromes.

PMID- 9254652
TI  - Identification of a Gal/GalNAc lectin in the protozoan Hartmannella vermiformis
      as a potential receptor for attachment and invasion by the Legionnaires' disease
      bacterium.
AB  - The Legionnaire's disease bacterium, Legionella pneumophila, is a facultative
      intracellular pathogen which invades and replicates within two evolutionarily
      distant hosts, free-living protozoa and mammalian cells. Invasion and
      intracellular replication within protozoa are thought to be major factors in the
      transmission of Legionnaire's disease. Although attachment and invasion of human
      macrophages by L. pneumophila is mediated in part by the complement receptors CR1
      and CR3, the protozoan receptor involved in bacterial attachment and invasion has
      not been identified. To define the molecular events involved in invasion of
      protozoa by L. pneumophila, we examined the role of protein tyrosine
      phosphorylation of the protozoan host Hartmannella vermiformis upon attachment
      and invasion by L. pneumophila. Bacterial attachment and invasion were associated
      with a time-dependent tyrosine dephosphorylation of multiple host cell proteins.
      This host cell response was highly specific for live L. pneumophila, required
      contact with viable bacteria, and was completely reversible following washing off
      the bacteria from the host cell surface. Tyrosine dephosphorylation of host
      proteins was blocked by a tyrosine phosphatase inhibitor but not by tyrosine
      kinase inhibitors. One of the tyrosine dephosphorylated proteins was identified
      as the 170-kD galactose/N-acetylgalactosamine-inhibitable lectin (Gal/GalNAc)
      using immunoprecipitation and immunoblotting by antibodies generated against the
      Gal/GalNAc lectin of the protozoan Entamoeba histolytica. This Gal/GalNAc
      inhibitable lectin has been shown previously to mediate adherence of E.
      histolytica to mammalian epithelial cells. Uptake of L. pneumophila by H.
      vermiformis was specifically inhibited by two monovalent sugars, Gal and GalNAc,
      and by mABs generated against the 170-kD lectin of E. histolytica. Interestingly,
      inhibition of invasion by Gal and GalNAc was associated with inhibition of
      bacterial-induced tyrosine dephosphorylation of H. vermiformis proteins. High
      stringency DNA hybridization confirmed the presence of the 170-kD lectin gene in
      H. vermiformis. We conclude that attachment of L. pneumophila to the H.
      vermiformis 170-kD lectin is required for invasion and is associated with
      tyrosine dephosphorylation of the Gal lectin and other host proteins. This is the
      first demonstration of a potential receptor used by L. pneumophila to invade
      protozoa.

PMID- 9254653
TI  - Degradation of mouse invariant chain: roles of cathepsins S and D and the
      influence of major histocompatibility complex polymorphism.
AB  - Antigen-presenting cells (APC) degrade endocytosed antigens into peptides that
      are bound and presented to T cells by major histocompatibility complex (MHC)
      class II molecules. Class II molecules are delivered to endocytic compartments by
      the class II accessory molecule invariant chain (Ii), which itself must be
      eliminated to allow peptide binding. The cellular location of Ii degradation, as
      well as the enzymology of this event, are important in determining the sets of
      antigenic peptides that will bind to class II molecules. Here, we show that the
      cysteine protease cathepsin S acts in a concerted fashion with other cysteine and
      noncysteine proteases to degrade mouse Ii in a stepwise fashion. Inactivation of
      cysteine proteases results in incomplete degradation of Ii, but the extent to
      which peptide loading is blocked by such treatment varies widely among MHC class
      II allelic products. These observations suggest that, first, class II molecules
      associated with larger Ii remnants can be converted efficiently to class II
      peptide complexes and, second, that most class II-associated peptides can still
      be generated in cells treated with inhibitors of cysteine proteases.
      Surprisingly, maturation of MHC class II in mice deficient in cathepsin D is
      unaffected, showing that this major aspartyl protease is not involved in
      degradation of Ii or in generation of the bulk of antigenic peptides.

PMID- 9254654
TI  - Src homology 2 protein tyrosine phosphatase (SHPTP2)/Src homology 2 phosphatase 2
      (SHP2) tyrosine phosphatase is a positive regulator of the interleukin 5 receptor
      signal transduction pathways leading to the prolongation of eosinophil survival.
AB  - Interleukin-5 (IL-5) regulates the growth and function of eosinophils. It induces
      rapid tyrosine phosphorylation of Lyn and Jak2 tyrosine kinases. The role of
      tyrosine phosphatases in IL-5 signal transduction has not been investigated. In
      this study, we provide first evidence that SH2 protein tyrosine phosphatase 2
      (SHPTP2) phosphotyrosine phosphatase plays a key role in prevention of eosinophil
      death by IL-5. We found that IL-5 produced a rapid activation and tyrosine
      phosphorylation of SHPTP2 within 1 min. The tyrosine phosphorylated SHPTP2 was
      complexed with the adapter protein Grb2 in IL-5-stimulated eosinophils.
      Furthermore, SHPTP2 appeared to physically associate with beta common (betac)
      chain of the IL-5 receptor (IL-5betacR). The association of SHPTP2 with IL
      5betacR was reconstituted using a synthetic phosphotyrosine-containing peptide,
      betac 605-624, encompassing tyrosine (Y)612. The binding to the phosphotyrosine
      containing peptide increased the phosphatase activity of SHPTP2, whereas the same
      peptide with the phosphorylated Y612--> F mutation did not activate SHPTP2. Only
      SHPTP2 antisense oligonucleotides, but not sense SHPTP2, could inhibit tyrosine
      phosphorylation of microtubule-associated protein kinase, and reverse the
      eosinophil survival advantage provided by IL-5. Therefore, we conclude that the
      physical association of SHPTP2 with the phosphorylated betac receptor and Grb2
      and its early activation are required for the coupling of the receptor to the Ras
      signaling pathway and for prevention of eosinophil death by IL-5.

PMID- 9254655
TI  - Murine salmonellosis studied by confocal microscopy: Salmonella typhimurium
      resides intracellularly inside macrophages and exerts a cytotoxic effect on
      phagocytes in vivo.
AB  - Salmonella typhimurium is considered a facultative intracellular pathogen, but
      its intracellular location in vivo has not been demonstrated conclusively. Here
      we describe the development of a new method to study the course of the
      histopathological processes associated with murine salmonellosis using confocal
      laser scanning microscopy of immunostained sections of mouse liver. Confocal
      microscopy of 30-micron-thick sections was used to detect bacteria after
      injection of approximately 100 CFU of S. typhimurium SL1344 intravenously into
      BALB/c mice, allowing salmonellosis to be studied in the murine model using more
      realistic small infectious doses. The appearance of bacteria in the mouse liver
      coincided in time and location with the infiltration of neutrophils in
      inflammatory foci. At later stages of disease the bacteria colocalized with
      macrophages and resided intracellularly inside these macrophages. Bacteria were
      cytotoxic for phagocytic cells, and apoptotic nuclei were detected
      immunofluorescently, whether phagocytes harbored intracellular bacteria or not.
      These data argue that Salmonella resides intracellularly inside macrophages in
      the liver and triggers cell death of phagocytes, processes which are involved in
      disease. This method is also applicable to other virulence models to examine
      infections at a cellular and subcellular level in vivo.

PMID- 9254656
TI  - The motheaten mutation rescues B cell signaling and development in CD45-deficient
      mice.
AB  - The cytosolic SHP-1 and transmembrane CD45 protein tyrosine phosphatases (PTP)
      play critical roles in regulating signal transduction via the B cell antigen
      receptor (BCR). These PTPs differ, however, in their effects on BCR function. For
      example, BCR-mediated mitogenesis is essentially ablated in mice lacking CD45
      (CD45(-)), but is enhanced in SHP-1-deficient motheaten (me) and viable motheaten
      (mev) mice. To determine whether these PTPs act independently or coordinately in
      modulating the physiologic outcome of BCR engagement, we assessed B cell
      development and signaling in CD45-deficient mev (CD45-/SHP-1-) mice. Here we
      report that the CD45-/SHP-1-) cells undergo appropriate induction of protein
      kinase activity, mitogen-activated protein kinase activation, and proliferative
      responses after BCR aggregation. However, BCR-elicited increases in the tyrosine
      phosphorylation of several SHP-1-associated phosphoproteins, including CD19, were
      substantially enhanced in CD45-/SHP-1-, compared to wild-type and CD45- cells. In
      addition, we observed that the patterns of cell surface expression of mu, delta,
      and CD5, which distinguish the PTP-deficient from normal mice, are largely
      restored to normal levels in the double mutant animals. These findings indicate a
      critical role for the balance of SHP-1 and CD45 activities in determining the
      outcome of BCR stimulation and suggest that these PTPs act in a coordinate
      fashion to couple antigen receptor engagement to B cell activation and
      maturation.

PMID- 9254657
TI  - Vascular adhesion protein 1 (VAP-1) mediates lymphocyte subtype-specific,
      selectin-independent recognition of vascular endothelium in human lymph nodes.
AB  - Interactions between lymphocyte surface receptors and their ligands on vascular
      endothelial cells regulate the exit of lymphocytes from the circulation. Distinct
      subsets of mononuclear cells bind to high endothelial venules (HEVs) in different
      lymphoid organs to a different extent, but the molecular mechanisms behind this
      selectivity have remained poorly characterized. Here we show that vascular
      adhesion protein-1 (VAP-1) mediates subtype-specific binding of CD8-positive T
      cells and natural killer cells to human endothelium. VAP-1-dependent,
      oligosaccharide-dependent peripheral lymph node (PLN) HEV adhesion under shear
      was independent of L-selectin, P-selectin glycoprotein ligand 1, and alpha4
      integrins, the known lymphocyte receptors involved in the initial recognition of
      endothelial cells. PLN HEV adhesion was also critically dependent on peripheral
      lymph node vascular addressins (PNAds), but lymphocyte L-selectin was absolutely
      required for PNAd binding. Most lymphocytes relied on both PNAd and VAP-1 in HEV
      binding. The overlapping function of L-selectin ligands and VAP-1 in PLN
      introduces a new control point into the lymphocyte extravasation process.
      Finally, intravital microscopy revealed that VAP-1 is involved in initial
      interactions between human lymphocytes and endothelial cells in inflamed rabbit
      mesenterial venules in vivo. In conclusion, VAP-1 is a novel contact-initiating
      ligand that discriminates between different subpopulations of mononuclear cells
      and is an appealing target for selective modulation of adhesion of CD8- and CD16
      positive effector cells.

PMID- 9254659
TI  - Requirement of Fas for the development of autoimmune diabetes in nonobese
      diabetic mice.
AB  - Insulin-dependent diabetes mellitus (IDDM) is assumed to be a T cell-mediated
      autoimmune disease. To investigate the role of Fas-mediated cytotoxicity in
      pancreatic beta cell destruction, we established nonobese diabetic (NOD)
      lymphoproliferation (lpr)/lpr mice lacking Fas. Out of three genotypes, female
      NOD-+/+ and NOD-+/lpr developed spontaneous diabetes by the age of 10 mo with the
      incidence of 68 and 62%, respectively. In contrast, NOD-lpr/lpr did not develop
      diabetes or insulitis. To further explore the role of Fas, adoptive transfer
      experiments were performed. When splenocytes were transferred from diabetic NOD,
      male NOD-+/+ and NOD-+/lpr developed diabetes with the incidence of 89 and 83%,
      respectively, whereas NOD-lpr/lpr did not show glycosuria by 12 wk after
      transfer. Severe mononuclear cell infiltration was revealed in islets of NOD-+/+
      and NOD-+/lpr, whereas islet morphology remained intact in NOD-lpr/lpr. These
      results suggest that Fas-mediated cytotoxicity is required to initiate beta cell
      autoimmunity in NOD mice. Fas-Fas ligand system might be critical for autoimmune
      beta cell destruction leading to IDDM.

PMID- 9254658
TI  - Kinetics of eotaxin generation and its relationship to eosinophil accumulation in
      allergic airways disease: analysis in a guinea pig model in vivo.
AB  - Challenge of the airways of sensitized guinea pigs with aerosolized ovalbumin
      resulted in an early phase of microvascular protein leakage and a delayed phase
      of eosinophil accumulation in the airway lumen, as measured using bronchoalveolar
      lavage (BAL). Immunoreactive eotaxin levels rose in airway tissue and BAL fluid
      to a peak at 6 h falling to low levels by 12 h. Eosinophil numbers in the tissue
      correlated with eotaxin levels until 6 h but eosinophils persisted until the last
      measurement time point at 24 h. In contrast, few eosinophils appeared in BAL over
      the first 12 h, major trafficking through the airway epithelium occurring at 12
      24 h when eotaxin levels were low. Constitutive eotaxin was present in BAL fluid.
      Both constitutive and allergen-induced eosinophil chemoattractant activity in BAL
      fluid was neutralized by an antibody to eotaxin. Allergen-induced eotaxin
      appeared to be mainly in airway epithelium and macrophages, as detected by
      immunostaining. Allergen challenge of the lung resulted in a rapid release of
      bone marrow eosinophils into the blood. An antibody to IL-5 suppressed bone
      marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin
      levels. Thus, IL-5 and eotaxin appear to cooperate in mediating a rapid transfer
      of eosinophils from the bone marrow to the lung in response to allergen
      challenge.

PMID- 9254660
TI  - Quantitative analysis reveals expansion of human hematopoietic repopulating cells
      after short-term ex vivo culture.
AB  - Ex vivo culture of human hematopoietic cells is a crucial component of many
      therapeutic applications. Although current culture conditions have been optimized
      using quantitative in vitro progenitor assays, knowledge of the conditions that
      permit maintenance of primitive human repopulating cells is lacking. We report
      that primitive human cells capable of repopulating nonobese diabetic (NOD)/severe
      combined immunodeficiency (SCID) mice (SCID-repopulating cells; SRC) can be
      maintained and/or modestly increased after culture of CD34+CD38- cord blood cells
      in serum-free conditions. Quantitative analysis demonstrated a 4- and 10-fold
      increase in the number of CD34+CD38- cells and colony-forming cells,
      respectively, as well as a 2- to 4-fold increase in SRC after 4 d of culture.
      However, after 9 d of culture, all SRC were lost, despite further increases in
      total cells, CFC content, and CD34+ cells. These studies indicate that caution
      must be exercised in extending the duration of ex vivo cultures used for
      transplantation, and demonstrate the importance of the SRC assay in the
      development of culture conditions that support primitive cells.

PMID- 9254661
TI  - Beta-adrenergic stimulation selectively inhibits long-lasting L-type calcium
      channel facilitation in hippocampal pyramidal neurons.
AB  - L-type calcium channels are abundant in hippocampal pyramidal neurons and are
      highly clustered at the base of the major dendrites. However, little is known of
      their function in these neurons. Single-channel recording using a low
      concentration of permeant ion reveals a long-lasting facilitation of L-type
      channel activity that is induced by a depolarizing prepulse or a train of action
      potential waveforms. This facilitation exhibits a slow rise, peaking 0.5-1 sec
      after the train and decaying over several seconds. We have termed this behavior
      "delayed facilitation," because of the slow onset. Delayed facilitation results
      from an increase in opening frequency and the recruitment of longer duration
      openings. This behavior is observed at all membrane potentials between -20 and 
      60 mV, with the induction and magnitude of facilitation being insensitive to
      voltage. beta-Adrenergic receptor activation blocks induction of delayed
      facilitation but does not significantly affect normal L-type channel activity.
      Delayed facilitation of L-type calcium channels provides a prolonged source of
      calcium entry at negative membrane potentials. This behavior may underlie calcium
      dependent events that are inhibited by beta-adrenergic receptor activation, such
      as the slow afterhyperpolarization in hippocampal neurons.

PMID- 9254662
TI  - Targeted transduction of CNS neurons with adenoviral vectors carrying
      neurotrophic factor genes confers neuroprotection that exceeds the transduced
      population.
AB  - Application of neurotrophic factors (NFs) to the cut stump of motor nerves of
      neonatal rats confers neuroprotection from trauma-induced neuronal death. To test
      whether motoneurons are capable of responding to endogenously produced NFs,
      facial motoneurons were genetically modified in vivo to express several NFs and
      then tested for their response to peripheral nerve damage. Replication-defective
      adenoviral vectors [Adv. Rous sarcoma virus (RSV)-nf] representing three families
      of NFs were constructed that carried genes for brain-derived neurotrophic factor
      (BDNF), ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic
      factor (GDNF), and nerve growth factor. Media from cultured cells transduced with
      Adv. RSV-nf contained NFs that supported the survival of cultured chick sensory
      neurons in the same manner as recombinant NF standards. When Adv.RSV-nf or an
      adenoviral vector containing the beta-galactosidase gene (Adv.RSV-beta-gal) were
      injected into the facial muscles of neonatal rats the vectors were retrogradely
      transported to the facial nucleus where the NFs or beta-gal were expressed. A
      fraction (approximately 10%) of the neurons were transduced as demonstrated by
      reverse transcriptase-PCR, histochemistry, and immunocytochemistry. In the case
      of Adv.RSV-BDNF, Adv.RSV-CNTF, and Adv.RSV-GDNF, a significant portion of the
      facial nucleus neurons was protected, 16.5, 18.2, and 53.3%, respectively, from
      death after axotomy, showing that neurons are capable of transporting the Adv.
      RSV-nf, expressing the recombinant NF genes, and responding to the NFs. In the
      case of Adv.RSV-GDNF, a greater number of facial nucleus motoneurons survived
      than were transduced, indicating that neighboring untransduced neurons were
      protected by the GDNF expressed by the transduced neurons by a paracrine
      mechanism.

PMID- 9254663
TI  - Slow recovery from inactivation of Na+ channels underlies the activity-dependent
      attenuation of dendritic action potentials in hippocampal CA1 pyramidal neurons.
AB  - Na+ action potentials propagate into the dendrites of pyramidal neurons driving
      an influx of Ca2+ that seems to be important for associative synaptic plasticity.
      During repetitive (10-50 Hz) firing, dendritic action potentials display a marked
      and prolonged voltage-dependent decrease in amplitude. Such a decrease is not
      apparent in somatic action potentials. We investigated the mechanisms of the
      different activity dependence of somatic and dendritic action potentials in CA1
      pyramidal neurons of adult rats using whole-cell and cell-attached patch-clamp
      methods. There were three main findings. First, dendritic Na+ currents decreased
      in amplitude when repeatedly activated by brief (2 msec) depolarizations.
      Recovery was slow and voltage-dependent. Second, Na+ currents decreased much less
      in somatic than in dendritic patches. Third, although K+ currents remained
      constant during trains, K+ currents were necessary for dendritic action potential
      amplitude to decrease in whole-cell experiments. These results suggest that
      regional differences in Na+ and K+ channels determine the differences in the
      activity dependence of somatic and dendritic action potential amplitudes.

PMID- 9254664
TI  - Murine astrocytes express a functional chemokine receptor.
AB  - Elevated levels of chemokines have been observed in various diseases of the CNS.
      Little is known, however, about how these chemokines affect parenchymal cells of
      the CNS. The current studies examine astrocyte chemotaxis to the mouse chemokine
      macrophage inflammatory protein-1alpha (MIP-1alpha). Murine astrocytes
      demonstrate directed migration along a chemical gradient in response to 10(-10)
      10(-8) M MIP-1alpha. Peak chemotactic responses are noted at 10(-9) M. MIP-1alpha
      induced astrocyte migration is specifically inhibitable with pertussis toxin,
      suggesting a role for Galphai proteins in the signaling process. RT-PCR and in
      situ hybridization were used to identify expression of the murine CCR1 MIP-1alpha
      receptor on astrocytes. Astrocytes contain mRNA for CCR1, but messages for CCR4
      and the orphan chemokine receptor MIP-1alphaR-like#1 were not detected. The
      combined results suggest that a functional chemokine receptor is expressed on
      resident cells of the CNS. We speculate that the interactions of chemokines with
      astrocytes are involved in inflammatory reactions of the CNS.

PMID- 9254665
TI  - Baculovirus expression provides direct evidence for heteromeric assembly of P2X2
      and P2X3 receptors.
AB  - P2X2 and P2X3 are subunits of P2X receptors, cation channels opened by binding
      extracellular ATP. cDNAs encoding P2X2 and P2X3 receptor subunits, each with one
      of two C-terminal epitope tags, were cloned into baculovirus. Virally infected
      insect cells (Spodoptera frugiperda) expressed moderate to high levels of the
      corresponding proteins, as detected by Western blotting, by the specific binding
      of [35S]ATP and by whole-cell recordings of membrane current evoked by ATP or
      alphabetamethylene-ATP. In cells infected at the same time with two viruses
      encoding P2X2 and P2X3 receptors, the two proteins could be cross
      immunoprecipitated with antibodies specific for either of the epitope tags. Whole
      cell recordings from these cells showed that ATP and alphabetamethylene-ATP
      evoked currents with agonist sensitivity and desensitization quite distinct from
      those observed when P2X2 or P2X3 receptors were expressed alone. The results
      offer a method to express large amounts of P2X receptor protein, and they provide
      direct evidence that P2X2 and P2X3 subunits assemble to form heteromeric channels
      having distinct properties from those formed as homomers.

PMID- 9254666
TI  - Neural agrin induces ectopic postsynaptic specializations in innervated muscle
      fibers.
AB  - Neural agrin, in the absence of a nerve terminal, can induce the activity
      resistant expression of acetylcholine receptor (AChR) subunit genes and the
      clustering of synapse-specific adult-type AChR channels in nonsynaptic regions of
      adult skeletal muscle fibers. Here we show that, when expression plasmids for
      neural agrin are injected into the extrasynaptic region of innervated muscle
      fibers, the following components of the postsynaptic apparatus are aggregated and
      colocalized with ectopic agrin-induced AChR clusters: laminin-beta2, MuSK,
      phosphotyrosine-containing proteins, beta-dystroglycan, utrophin, and rapsyn.
      These components have been implicated to play a role in the differentiation of
      neuromuscular junctions. Furthermore, ErbB2 and ErbB3, which are thought to be
      involved in the regulation of neurally induced AChR subunit gene expression, were
      colocalized with agrin-induced AChR aggregates at ectopic nerve-free sites. The
      postsynaptic muscle membrane also contained a high concentration of voltage-gated
      Na+ channels as well as deep, basal lamina-containing invaginations comparable to
      the secondary synaptic folds of normal endplates. The ability to induce AChR
      aggregation in vivo was not observed in experiments with a muscle-specific agrin
      isoform. Thus, a motor neuron-specific agrin isoform is sufficient to induce a
      full ectopic postsynaptic apparatus in muscle fibers kept electrically active at
      their original endplate sites.

PMID- 9254667
TI  - Agonist-specific coupling of a cloned Drosophila melanogaster D1-like dopamine
      receptor to multiple second messenger pathways by synthetic agonists.
AB  - The mechanism of coupling of a cloned Drosophila D1-like dopamine receptor,
      DopR99B, to multiple second messenger systems when expressed in Xenopus oocytes
      is described. The receptor is coupled directly to the generation of a rapid,
      transient intracellular Ca2+ signal, monitored as changes in inward current
      mediated by the oocyte endogenous Ca2+-activated chloride channel, by a pertussis
      toxin-insensitive G-protein-coupled pathway. The more prolonged receptor-mediated
      changes in adenylyl cyclase activity are generated by an independent G-protein
      coupled pathway that is pertussis toxin-sensitive but calcium-independent, and
      Gbetagamma-subunits appear to be involved in the transduction of this response.
      This is the first evidence for the direct coupling of a cloned D1-like dopamine
      receptor both to the activation of adenylyl cyclase and to the initiation of an
      intracellular Ca2+ signal. The pharmacological profile of both second messenger
      effects is identical for a range of naturally occurring catecholamine ligands
      (dopamine > norepinephrine > epinephrine) and for the blockade of dopamine
      responses by a range of synthetic antagonists. However, the pharmacological
      profiles of the two second messenger responses differ for a range of synthetic
      agonists. Thus, the receptor exhibits agonist-specific coupling to second
      messenger systems for synthetic agonists. This feature could provide a useful
      tool in the genetic analysis of the roles of the multiple second messenger
      pathways activated by this receptor, given the likely involvement of dopamine in
      the processes of learning and memory in the insect nervous system.

PMID- 9254668
TI  - Differential expression of alpha-bungarotoxin-sensitive neuronal nicotinic
      receptors in adrenergic chromaffin cells: a role for transcription factor Egr-1.
AB  - Adrenomedullary chromaffin cells express at least two subtypes of acetylcholine
      nicotinic receptors, which differ in their sensitivity to the snake toxin alpha
      bungarotoxin. One subtype is involved in the activation step of the catecholamine
      secretion process and is not blocked by the toxin. The other is alpha
      bungarotoxin-sensitive, and its functional role has not yet been defined. The
      alpha7 subunit is a component of this subtype. Autoradiography of bovine adrenal
      gland slices with alpha-bungarotoxin indicates that these receptors are
      restricted to medullary areas adjacent to the adrenal cortex and colocalize with
      the enzyme phenylethanolamine N-methyl transferase (PNMT), which confers the
      adrenergic phenotype to chromaffin cells. Transcripts corresponding to the alpha7
      subunit also are localized exclusively to adrenergic cells. To identify possible
      transcriptional regulatory elements of the alpha7 subunit gene involved in the
      restricted expression of nicotinic receptors, we isolated and characterized its
      5' flanking region, revealing putative binding sites for the immediate early gene
      transcription factor Egr-1, which is known to activate PNMT expression. In
      reporter gene transfection experiments, Egr-1 increased alpha7 promoter activity
      by up to sevenfold. Activation was abolished when the most promoter-proximal of
      the Egr-1 sites was mutated, whereas modification of a close upstream site
      produced a partial decrease of the Egr-1 response. Because Egr-1 was found to be
      expressed exclusively in adrenergic cells, we suggest that this transcription
      factor may be part of a common mechanism involved in the induction of the
      adrenergic phenotype and the differential expression of alpha-bungarotoxin
      sensitive nicotinic receptors in the adrenal gland.

PMID- 9254669
TI  - Kappa-opioid receptor activation modulates Ca2+ currents and secretion in
      isolated neuroendocrine nerve terminals.
AB  - Whole-cell patch-clamp recordings were performed together with time-resolved
      measurements of membrane capacitance (Cm) in nerve terminals acutely dissociated
      from neurohypophysis of adult rats to investigate modulation of Ca2+ currents and
      secretion by activation of opioid receptors. Bath superfusion of the kappa-opioid
      agonists U69,593 (0.3-1 microM), dynorphin A (1 microM), or U50,488H (1-3 microM)
      reversibly suppressed the peak amplitude of Ca2+ currents 32. 7 +/- 2.7% (in 41
      of 56 terminals), 37.4 +/- 5.3% (in 5 of 8 terminals), and 33.5 +/- 8.1% (in 5 of
      10 terminals), respectively. In contrast, tests in 11 terminals revealed no
      effect of the mu-opioid agonist [D-Pen2,5]-enkephalin (1-3 microM; n = 7) or of
      the delta-agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (1 microM; n = 4) on Ca2+
      currents. Three components of high-threshold current were distinguished on the
      basis of their sensitivity to blockade by omega-conotoxin GVIA, nicardipine, and
      omega-conotoxin MVIIC: N-, L-, and P/Q-type current, respectively. Administration
      of U69,593 inhibited N-type current in these nerve terminals on average 32%,
      whereas L-type current was reduced 64%, and P/Q-type current was inhibited 28%.
      Monitoring of changes in Cm in response to brief depolarizing steps revealed that
      the kappa-opioid-induced reductions in N-, L-, or P/Q-type currents were
      accompanied by attenuations in two kinetically distinct components of Ca2+
      dependent exocytotic release. These data provide strong evidence of a functional
      linkage between blockade of Ca2+ influx through voltage-dependent Ca2+ channels
      and inhibitory modulation of release by presynaptic opioid receptors in mammalian
      central nerve endings.

PMID- 9254670
TI  - Adenoviral vector-mediated expression of B-50/GAP-43 induces alterations in the
      membrane organization of olfactory axon terminals in vivo.
AB  - B-50/GAP-43 is an intraneuronal membrane-associated growth cone protein with an
      important role in axonal growth and regeneration. By using adenoviral vector
      directed expression of B-50/GAP-43 we studied the morphogenic action of B-50/GAP
      43 in mature primary olfactory neurons that have established functional synaptic
      connections. B-50/GAP-43 induced gradual alterations in the morphology of
      olfactory synapses. In the first days after overexpression, small protrusions
      originating from the preterminal axon shaft and from the actual synaptic bouton
      were formed. With time the progressive formation of multiple ultraterminal
      branches resulted in axonal labyrinths composed of tightly packed sheaths of
      neuronal membrane. Thus, B-50/GAP-43 is a protein that can promote neuronal
      membrane expansion at synaptic boutons. This function of B-50/GAP-43 suggests
      that this protein may subserve an important role in ongoing structural synaptic
      plasticity in adult neurons and in neuronal membrane repair after injury to
      synaptic fields.

PMID- 9254671
TI  - Assembly of GABAA receptors composed of alpha1 and beta2 subunits in both
      cultured neurons and fibroblasts.
AB  - GABAA receptors are believed to be pentameric hetero-oligomers, which can be
      constructed from six subunits (alpha, beta, gamma, delta, epsilon, and rho) with
      multiple members, generating a large potential for receptor heterogeneity. The
      mechanisms used by neurons to control the assembly of these receptors, however,
      remain unresolved. Using Semliki Forest virus expression we have analyzed the
      assembly of 9E10 epitope-tagged receptors comprising alpha1 and beta2 subunits in
      baby hamster kidney cells and cultured superior cervical ganglia neurons.
      Homomeric subunits were retained within the endoplasmic reticulum, whereas
      heteromeric receptors were able to access the cell surface in both cell types.
      Sucrose density gradient fractionation demonstrated that the homomeric subunits
      were incapable of oligomerization, exhibiting 5 S sedimentation coefficients.
      Pulse-chase analysis revealed that homomers were degraded, with half-lives of
      approximately 2 hr for both the alpha1((9E10)) and beta2((9E10)) subunits.
      Oligomerization of the alpha1((9E10)) and beta2((9E10)) subunits was evident, as
      demonstrated by the formation of a stable 9 S complex, but this process seemed
      inefficient. Interestingly the appearance of cell surface receptors was slow,
      lagging up to 6 hr after the formation of the 9 S receptor complex. Using
      metabolic labeling a ratio of alpha1((9E10)):beta2((9E10)) of 1:1 was found in
      this 9 S fraction. Together the results suggest that GABAA receptor assembly
      occurs by similar mechanisms in both cell types, with retention in the
      endoplasmic reticulum featuring as a major control mechanism to prevent
      unassembled receptor subunits accessing the cell surface.

PMID- 9254672
TI  - Quantitative single-cell-reverse transcription-PCR demonstrates that A-current
      magnitude varies as a linear function of shal gene expression in identified
      stomatogastric neurons.
AB  - Different Shaker family alpha-subunit genes generate distinct voltage-dependent
      K+ currents when expressed in heterologous expression systems. Thus it generally
      is believed that diverse neuronal K+ current phenotypes arise, in part, from
      differences in Shaker family gene expression among neurons. It is difficult to
      evaluate the extent to which differential Shaker family gene expression
      contributes to endogenous K+ current diversity, because the specific Shaker
      family gene or genes responsible for a given K+ current are still unknown for
      nearly all adult neurons. In this paper we explore the role of differential
      Shaker family gene expression in creating transient K+ current (IA) diversity in
      the 14-neuron pyloric network of the spiny lobster, Panulirus interruptus. We
      used two-electrode voltage clamp to characterize the somatic IA in each of the
      six different cell types of the pyloric network. The size, voltage-dependent
      properties, and kinetic properties of the somatic IA vary significantly among
      pyloric neurons such that the somatic IA is unique in each pyloric cell type.
      Comparing these currents with the IAs obtained from oocytes injected with
      Panulirus shaker and shal cRNA (lobster Ishaker and lobster Ishal, respectively)
      reveals that the pyloric cell IAs more closely resemble lobster Ishal than
      lobster Ishaker. Using a novel, quantitative single-cell-reverse transcription
      PCR method to count the number of shal transcripts in individual identified
      pyloric neurons, we found that the size of the somatic IA varies linearly with
      the number of endogenous shal transcripts. These data suggest that the shal gene
      contributes substantially to the peak somatic IA in all neurons of the pyloric
      network.

PMID- 9254673
TI  - Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal
      ganglion neurons.
AB  - To determine the subunit composition of high-affinity kainate receptors in native
      neurons is a challenging problem because of the expression of more than one GluR
      subunit. In the present study the question of whether GluR5 and/or GluR6 subunits
      combine with KA-1 or KA-2 subunits in vivo is addressed by performing detailed
      physiological, pharmacological, and molecular characterization of functional
      kainate receptor channels in acutely dissociated trigeminal ganglion (TG)
      neurons. The results show that (1) smaller diameter TG neurons (<30 microm)
      respond to L-glutamate and kainate, and the currents gated by kainate desensitize
      with prolonged agonist exposure; (2) all kainate receptor subunits are detected
      to some extent by reverse transcriptase-PCR, whereas glutamate receptor subunits
      GluR5 and KA-2 are expressed at high levels in the TG; (3) there is an obvious
      similarity between the features of native kainate receptor channels in TG neurons
      and of heteromeric recombinant GluR5(R)/KA-2 channels in pharmacological
      properties, desensitization, rectification, ion permeability, and mean channel
      conductance; and (4) the age-dependent increase in GluR5 and KA-2 RNA levels in
      the TG is correlated well with an increased number of kainate-sensitive cells
      during postnatal development. Our data suggest that the heteromeric GluR5/KA2
      combination actually occurs in TG neurons and give a clue as to the subunit
      composition of native kainate receptor channels.

PMID- 9254674
TI  - T-type Ca2+ current properties are not modified by Ca2+ channel beta subunit
      depletion in nodosus ganglion neurons.
AB  - At the molecular level, our knowledge of the low voltage-activated Ca2+ channel
      (T-type) has made little progress. Using an antisense strategy, we investigated
      the possibility that the T-type channels have a structure similar to high voltage
      activated Ca2+ channels. It is assumed that high voltage-activated channels are
      made of at least three components: a pore forming alpha1 subunit combined with a
      cytoplasmic modulatory beta subunit and a primarily extracellular alpha2delta
      subunit. We have examined the effect of transfecting cranial primary sensory
      neurons with generic anti-beta antisense oligonucleotides. We show that in this
      cell type, blocking expression of all known beta gene products does not affect T
      type current, although it greatly decreases the current amplitude of high voltage
      activated channels and modifies their voltage dependence. This suggests that beta
      subunits are likely not constitutive of T-type Ca2+ channels in this cell type.

PMID- 9254675
TI  - Developing neonatal rat sympathetic and sensory neurons differ in their
      regulation of 5-HT3 receptor expression.
AB  - Serotonin 5-HT3 receptors (5-HT3Rs) are ligand-gated ion channels expressed by
      many peripheral neurons and are involved in several physiological processes. To
      learn more about the developmental regulation of 5-HT3R expression, we
      investigated rat sympathetic and vagal sensory neurons. We found that sympathetic
      and sensory neurons differ in their regulation of 5-HT3R expression during early
      postnatal life and as these neurons develop in culture. In SCG neurons 5-HT3R
      transcript levels are low at postnatal day 1 (P1) and increase 7.5-fold by P21;
      this increase occurs even after elimination of preganglionic innervation. In
      comparison, 5-HT3R mRNA levels in P1 nodose neurons are over 14-fold greater than
      in P1 SCG and change little by P21. We show that 5-HT3R transcript levels in
      nodose neurons depend on intact target innervation and drop by 60% after axotomy.
      When P1 SCG neurons develop in culture, we observed a significant increase in 5
      HT3R expression: after 7 d in culture, transcript levels increase ninefold versus
      a threefold increase for neurons developing for 7 d in vivo. In contrast, 5-HT3R
      mRNA levels in cultured nodose neurons drop by 70% within 24 hr; however, this
      drop is transient. After 2 d, transcript levels begin to increase, and after 7 d,
      they are above initial values. We show that this delayed increase in 5-HT3R
      expression depends on neurotrophins. In both nodose and sympathetic neurons we
      found that the changes in 5-HT3R gene expression correlate directly with the
      appearance of 5-HT-evoked current densities.

PMID- 9254676
TI  - Prolonged sodium channel inactivation contributes to dendritic action potential
      attenuation in hippocampal pyramidal neurons.
AB  - During low-frequency firing, action potentials actively invade the dendrites of
      CA1 pyramidal neurons. At higher firing rates, however, activity-dependent
      processes result in the attenuation of back-propagating action potentials, and
      propagation failures occur at some dendritic branch points. We tested two major
      hypotheses related to this activity-dependent attenuation of back-propagating
      action potentials: (1) that it is mediated by a prolonged form of sodium channel
      inactivation and (2) that it is mediated by a persistent dendritic shunt
      activated by back-propagating action potentials. We found no evidence for a
      persistent shunt, but we did find that cumulative, prolonged inactivation of
      sodium channels develops during repetitive action potential firing. This
      inactivation is significant after a single action potential and continues to
      develop during several action potentials thereafter, until a steady-state sodium
      current is established. Recovery from this form of inactivation is much slower
      than its induction, but recovery can be accelerated by hyperpolarization. The
      similarity of these properties to the time and voltage dependence of attenuation
      and recovery of dendritic action potentials suggests that dendritic sodium
      channel inactivation contributes to the activity dependence of action potential
      back-propagation in CA1 neurons. Hence, the biophysical properties of dendritic
      sodium channels will be important determinants of action potential-mediated
      effects on synaptic integration and plasticity in hippocampal neurons.

PMID- 9254677
TI  - Alteration of Ca2+ dependence of neurotransmitter release by disruption of Ca2+
      channel/syntaxin interaction.
AB  - Presynaptic N-type calcium channels interact with syntaxin and synaptosome
      associated protein of 25 kDa (SNAP-25) through a binding site in the
      intracellular loop connecting domains II and III of the alpha1 subunit. This
      binding region was loaded into embryonic spinal neurons of Xenopus by early
      blastomere injection. After culturing, synaptic transmission of peptide-loaded
      and control cells was compared by measuring postsynaptic responses under
      different external Ca2+ concentrations. The relative transmitter release of
      injected neurons was reduced by approximately 25% at physiological Ca2+
      concentration, whereas injection of the corresponding region of the L-type Ca2+
      channel had virtually no effect. When applied to a theoretical model, these
      results imply that 70% of the formerly linked vesicles have been uncoupled after
      action of the peptide. Our data suggest that severing the physical interaction
      between presynaptic calcium channels and synaptic proteins will not prevent
      synaptic transmission at this synapse but will make it less efficient by shifting
      its Ca2+ dependence to higher values.

PMID- 9254678
TI  - Evidence that the homeodomain protein Gtx is involved in the regulation of
      oligodendrocyte myelination.
AB  - We have investigated the patterns of postnatal brain expression and DNA binding
      of Gtx, a homeodomain transcription factor. Gtx mRNA accumulates in parallel with
      the RNAs encoding the major structural proteins of myelin, myelin basic protein
      (MBP), and proteolipid protein (PLP) during postnatal brain development; Gtx mRNA
      decreases in parallel with MBP and PLP mRNAs in the brains of myelin-deficient
      rats, which have a point mutation in the PLP gene. Gtx mRNA is expressed in
      differentiated, postmitotic oligodendrocytes but is not found in oligodendrocyte
      precursors or astrocytes. These data thus demonstrate that Gtx is expressed
      uniquely in differentiated oligodendrocytes in postnatal rodent brain and that
      its expression is regulated in parallel with the major myelin protein mRNAs,
      encoding MBP and PLP, under a variety of physiologically relevant circumstances.
      Using a Gtx fusion protein produced in bacteria, we have confirmed that Gtx is a
      sequence-specific DNA-binding protein, which binds DNA sequences containing a
      core AT-rich homeodomain binding site. Immunoprecipitation of labeled DNA
      fragments encoding either the MBP or PLP promoter regions with this fusion
      protein has identified several Gtx-binding fragments, and we have confirmed these
      data using an electrophoretic mobility shift assay. In this way we have
      identified four Gtx binding sites within the first 750 bp of the MBP promoter and
      four Gtx binding sites within the first 1. 3 kb of the PLP promoter. In addition,
      inspection of the PLP promoter sequence demonstrates the presence of six
      additional Gtx binding sites. These data, taken together, strongly suggest that
      Gtx is important for the function of differentiated oligodendrocytes and may be
      involved in the regulation of myelin-specific gene expression.

PMID- 9254679
TI  - Ionized intracellular calcium concentration predicts excitotoxic neuronal death:
      observations with low-affinity fluorescent calcium indicators.
AB  - Cytosolic calcium ([Ca2+]i) is an important mediator of neuronal signal
      transduction, participating in diverse biochemical reactions that elicit changes
      in synaptic efficacy, metabolic rate, and gene transcription. Excessive [Ca2+]i
      also has been implicated as a cause of acute neuronal injury, although
      measurement of [Ca2+]i in living neurons by fluorescent calcium indicators has
      not consistently demonstrated a correlation between [Ca2+]i and the likelihood of
      neuronal death after a variety of potentially lethal insults. Using fluorescence
      videomicroscopy and microinjected calcium indicators, we measured [Ca2+]i in
      cultured cortical neurons during intense activation with either NMDA (300 microM)
      or AMPA (450 microM). At these concentrations NMDA killed >80% of the cultured
      neurons by the next day, whereas neuronal death from AMPA was <20%. Using the
      conventional calcium indicator, fura-2/AM, we estimated [Ca2+]i elevations to be
      approximately 300-400 nM during exposure to either glutamate agonist. In
      contrast, indicators with lower affinity for calcium, benzothiazole coumarin
      (BTC), and fura-2/dextran reported [Ca2+]i levels >5 microM during lethal NMDA
      exposure, but [Ca2+]i levels were <1.5 microM during nonlethal activation of AMPA
      receptors or voltage-gated calcium channels. Fura-2 reported [Ca2+]i responses
      during brief exposure to glutamate, NMDA, AMPA, kainate, and elevated
      extracellular K+ between 0.5 and 1 microM. With the use of BTC, only NMDA and
      glutamate exposures resulted in micromolar [Ca2+]i levels. Neurotoxic glutamate
      receptor activation is associated with sustained, micromolar [Ca2+]i elevation.
      The widely used calcium indicator fura-2 selectively underestimates [Ca2+]i,
      depending on the route of entry, even at levels that appear to be within its
      range of detection.

PMID- 9254680
TI  - Expression of zinc transporter gene, ZnT-1, is induced after transient forebrain
      ischemia in the gerbil.
AB  - To elucidate the molecular mechanisms underlying neuronal death after transient
      forebrain ischemia, we cloned genes expressed after transient forebrain ischemia
      in the Mongolian gerbil by a differential display method. A gerbil homolog of rat
      zinc transporter, ZnT-1, which transports intracellular Zn2+ out of cells, was
      isolated. Its expression became detectable exclusively in pyramidal neurons of
      the CA1 region 12 hr after ischemia and reached a maximum from day 1 to day 2 as
      shown by in situ hybridization. By day 7, expression had disappeared entirely
      from the cells in the CA1 region, because the neurons had died. No other brain
      regions exhibited such a significant level of ZnT-1 mRNA expression during this
      period. Zn2+ was shown to accumulate in CA1 pyramidal neurons expressing ZnT-1
      mRNA after the ischemia by using zinquin, a zinc-specific fluorescent dye. When
      primary hippocampal neurons were exposed to a high dose of Zn2+, ZnT-1 mRNA
      accumulated. These results suggest that the induction of ZnT-1 mRNA observed in
      CA1 neurons was caused by an increase in the intracellular Zn2+ concentration. It
      was reported recently that Zn2+ chelator blocked neuronal death after ischemia
      and that the influx of Zn2+ might be a key mechanism underlying neuronal death.
      The induction of ZnT-1 mRNA in CA1 pyramidal neurons fated to die after transient
      ischemia is of interest to the study of postischemic events and the molecular
      mechanisms underlying delayed neuronal death.

PMID- 9254681
TI  - Subunit composition, kinetic, and permeation properties of AMPA receptors in
      single neocortical nonpyramidal cells.
AB  - Native AMPA receptors (AMPARs) were investigated in neocortical fast-spiking (FS)
      and regular-spiking nonpyramidal (RSNP) cells. The onset of and recovery from
      desensitization as well as current rectification and single-channel conductance
      were studied by using fast glutamate application to outside-out patches. The
      GluR1-4 subunit, flip/flop splicing, and R/G editing expression patterns of
      functionally characterized cells were determined by single-cell reverse
      transcription-PCR to correlate the subunit composition of native AMPARs with
      their functional properties. Our sample, mostly constituted by RSNP neurons,
      predominantly expressed GluR3 flip and GluR2 flop. In individual cells, flip/flop
      splicing of each subunit appeared to be regulated independently, whereas for R/G
      editing all subunits were either almost fully edited or unedited. We confirmed
      that the relative GluR2 expression controls the permeation properties of native
      AMPARs, whereas none of the single molecular parameters considered appeared to be
      a key determinant of the kinetics. FS neurons displayed AMPARs with relatively
      homogeneous functional properties characterized by fast desensitization, slow
      recovery from desensitization, marked inward rectification, and large single
      channel conductance. In contrast, these parameters varied over a wide range in
      RSNP neurons, and their combination resulted in various AMPAR functional
      patterns. Indeed, in different cells, fast or slow desensitization was found to
      be associated with either slow or fast recovery from desensitization. Similarly,
      fast or slow kinetics was associated with either strong or weak rectification.
      Our results suggest that kinetic and permeation properties of native AMPARs can
      be regulated independently in cortical neurons and probably do not have the same
      molecular determinants.

PMID- 9254682
TI  - Glial growth factor rescues Schwann cells of mechanoreceptors from denervation
      induced apoptosis.
AB  - Golgi tendon organs and Pacinian corpuscles are peripheral mechanoreceptors that
      disappear after denervation during a critical period in early postnatal
      development. Even if regeneration is allowed to occur, Golgi tendon organs do not
      reform, and the reformation of Pacinian corpuscles is greatly impaired. The
      sensory nerve terminals of both types of mechanoreceptors are closely associated
      with Schwann cells. Here we investigate the changes in the Schwann cells found in
      Golgi tendon organs and Pacinian corpuscles after nerve resection in the early
      neonatal period. We report that denervation induces the apoptotic death of these
      Schwann cells and that this apoptosis can be prevented by administration of a
      soluble form of neuregulin, glial growth factor 2. Schwann cells associated with
      these mechanoreceptors are immunoreactive for the neuregulin receptors erbB2,
      erbB3, and erbB4, and the sensory nerve terminals are immunoreactive for
      neuregulin. Our results suggest that Schwann cells in developing sensory end
      organs are trophically dependent on sensory axon terminals and that an axon
      derived neuregulin mediates this trophic interaction. The denervation-induced
      death of mechanoreceptor Schwann cells is correlated with deficiencies in the re
      establishment of these sensory end organs by regenerating axons.

PMID- 9254683
TI  - Brain-derived neurotrophic factor enhances long-term potentiation in rat visual
      cortex.
AB  - Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of
      the nerve growth factor (NGF) gene family, have been suggested to play a role in
      experience-dependent modification of neural networks in the developing nervous
      system. In this study we addressed the question of whether these neurotrophins
      are involved in long-term potentiation (LTP) in developing visual cortex. We
      recorded layer II/III field potentials and whole-cell currents evoked by test
      stimulation of layer IV at 0.1 Hz in visual cortical slices prepared from young
      rats (postnatal day 15-25) and observed effects of BDNF, NT-3, and NGF on these
      responses. Then we analyzed the effects of these neurotrophins on LTP induced by
      tetanic (Theta-burst type) stimulation of layer IV. We found that BDNF at 200
      ng/ml potentiated field potentials and EPSCs in most cases and that this
      potentiation lasted after cessation of the BDNF application. At the concentration
      of 20 ng/ml, BDNF did not show such an effect, but it enhanced the magnitude of
      expressed LTP. On the other hand, NT-3 and NGF had none of these effects.
      Immunohistochemical staining of slices with antibody against BDNF showed that
      exogenous BDNF penetrated into the whole slice within approximately 5 min of its
      application. The actions of BDNF were blocked by preincubation of slices with
      TrkB-IgG fusion protein, a BDNF scavenger, or coapplication of K252a, an
      inhibitor for receptor tyrosine kinases. TrkB-IgG or K252a itself completely
      blocked LTP, suggesting that endogenous BDNF or another TrkB ligand plays a role
      in LTP in the developing visual cortex.

PMID- 9254684
TI  - Differential expression of distinct members of Rho family GTP-binding proteins
      during neuronal development: identification of Rac1B, a new neural-specific
      member of the family.
AB  - Previous studies on small GTP-binding proteins of the Rho family have revealed
      their involvement in the organization of cell actin cytoskeleton. The function of
      these GTPases during vertebrate development is not known. With the aim of
      understanding the possible role of these proteins during neuronal development, we
      have cloned and sequenced five members expressed in developing chick neural
      retinal cells. We have identified four chicken genes, cRhoA, cRhoB, cRhoC, and
      cRac1A, homologous to known human genes, and a novel Rac gene, cRac1B. Analysis
      of the distribution of four of the identified transcripts in chicken embryos
      shows for the first time high levels of expression of Rho family genes in the
      vertebrate developing nervous system, with distinct patterns of distribution for
      the different transcripts. In particular, cRhoA and cRac1A gene expression
      appeared ubiquitous in the whole embryo, and the cRhoB transcript was more
      prominent in populations of neurons actively extending neurites, whereas the
      newly identified cRac1B gene was homogeneously expressed only in the developing
      nervous system. Temporal analysis of the expression of the five genes suggests a
      correlation with the morphogenetic events occurring within the developing retina
      and the retinotectal pathway. Expression of an epitope-tagged cRac1B in retinal
      neurons showed a diffuse distribution of the protein in the cell body and along
      neurites. Taken as a whole, our results suggest important roles for ubiquitous
      and neural-specific members of the Rho family in the acquisition of the mature
      neuronal phenotype.

PMID- 9254685
TI  - Muscarinic induction of synchronous population activity in the entorhinal cortex.
AB  - Oscillation and synchronization of neural activity is important in normal brain
      function but is also relevant to epileptogenesis. One of the most frequent forms
      of epilepsy originates in temporal lobe circuitry of which the entorhinal cortex
      (EC) is crucial. Because muscarinic receptor activation promotes oscillatory
      dynamics in EC neurons, we investigated in a brain slice preparation the effects
      of carbachol (CCh) on oscillatory population activity in the EC. We found that
      CCh produced epileptiform activity in EC, which according to field profile and
      current source density analysis was usually driven by layer V. In addition,
      localized CCh application and surgical isolation experiments demonstrated that EC
      layer II, but not layer III, can also independently generate synchronous
      population activity. Intracellular recordings from EC principal cells during
      epileptiform activity demonstrated large-amplitude, synaptically driven
      depolarizing events and bursts of action potentials synchronized to the field
      spikes. In layer II neurons, the depolarizing events had a multiphasic reversal
      potential that suggested concurrent glutamatergic and GABAergic synaptic input.
      Interestingly, although the epileptiform activity required activation of AMPA but
      not NMDA receptors, small-amplitude field spikes persisted during block of fast
      excitatory neurotransmission. These field spikes were correlated to large
      amplitude IPSPs in layer II neurons, and both activities were abolished by GABAA
      receptor antagonism. Thus, in response to muscarinic activation, pools of EC
      interneurons discharge synchronously by a mechanism not necessarily involving
      principal cell activation. Given the differential projection pattern of EC layers
      V and II toward the neocortex and hippocampus, respectively, their robust
      epileptogenic character may be of major importance in temporal lobe epilepsy.

PMID- 9254686
TI  - Spatial and temporal expression of the period and timeless genes in the
      developing nervous system of Drosophila: newly identified pacemaker candidates
      and novel features of clock gene product cycling.
AB  - The circadian timekeeping system of Drosophila functions from the first larval
      instar (L1) onward but is not known to require the expression of clock genes in
      larvae. We show that period (per) and timeless (tim) are rhythmically expressed
      in several groups of neurons in the larval CNS both in light/dark cycles and in
      constant dark conditions. Among the clock gene-expressing cells there is a subset
      of the putative pacemaker neurons, the "lateral neurons" (LNs), that have been
      analyzed mainly in adult flies. Like the adult LNs, the larval ones are also
      immunoreactive to a peptide called pigment-dispersing hormone. Their putative
      dendritic trees were found to be in close proximity to the terminals of the
      larval optic nerve Bolwig's nerve, possibly receiving photic input from the
      larval eyes. The LNs are the only larval cells that maintain a strong cycling in
      PER from L1 onward, throughout metamorphosis and into adulthood. Therefore, they
      are the best candidates for being pacemaker neurons responsible for the larval
      "time memory" (inferred from previous experiments). In addition to the LNs, a
      subset of the larval dorsal neurons (DNLs) expresses per and tim. Intriguingly,
      two neurons of this DNL group cycle in PER and TIM immunoreactivity almost in
      antiphase to the other DNLs and to the LNs. Thus, the temporal expression of per
      and tim are regulated differentially in different cells. Furthermore, the light
      sensitivity associated with levels of the TIM protein is different from that in
      the heads of adult Drosophila.

PMID- 9254687
TI  - Dopaminergic neurons intrinsic to the primate striatum.
AB  - Intrinsic, striatal tyrosine hydroxylase-immunoreactive (TH-i) cells have
      received little consideration. In this study we have characterized these neurons
      and their regulatory response to nigrostriatal dopaminergic deafferentation. TH-i
      cells were observed in the striatum of both control and 1-methyl-4-phenyl-1,2,3,
      6-tetrahydropyridine (MPTP)-treated monkeys; TH-i cell counts, however, were 3.5
      fold higher in the striatum of MPTP-lesioned monkeys. To establish the
      dopaminergic nature of the TH-i cells, sections were double-labeled with
      antibodies to dopamine transporter (DAT). Immunofluorescence studies demonstrated
      that nearly all TH-i cells were double-labeled with DAT, suggesting that they
      contain the machinery to be functional dopaminergic neurons. Two types of TH-i
      cells were identified in the striatum: small, aspiny, bipolar cells with varicose
      dendrites and larger spiny, multipolar cells. The aspiny cells, which were more
      prevalent, corresponded morphologically to the GABAergic interneurons of the
      striatum. Double-label immunofluorescence studies using antibodies to TH and
      glutamate decarboxylase (GAD67), the synthetic enzyme for GABA, showed that 99%
      of the TH-i cells were GAD67-positive. Very few (<1%) of the TH-i cells, however,
      were immunoreactive for the calcium-binding proteins calbindin and parvalbumin.
      In summary, these results demonstrate that the dopaminergic cell population of
      the striatum responds to dopamine denervation by increasing in number, apparently
      to compensate for loss of extrinsic dopaminergic innervation. Moreover, this
      population of cells corresponds largely with the intrinsic GABAergic cells of the
      striatum. This study also suggests that the adult primate striatum does retain
      some intrinsic capacity to compensate for dopaminergic cell loss.

PMID- 9254688
TI  - The effect of aging on experience-dependent plasticity of hippocampal place
      cells.
AB  - The firing characteristics of 1437 CA1 pyramidal neurons were studied in relation
      to both spatial location and the phase of the theta rhythm in healthy young and
      old rats performing a simple spatial task on a rectangular track. The old rats
      had previously been found to be deficient on the Morris spatial learning task.
      Age effects on the theta rhythm per se were minimal. Theta amplitude and
      frequency during rapid eye movement sleep were virtually identical. During
      behavior, theta frequency was slightly reduced with age. In both groups, cell
      firing occurred at progressively earlier phases of the theta rhythm as the rat
      traversed the place field of the cell (i. e., there was "phase precession," as
      reported by others). The net phase shift did not differ between age groups. The
      main finding of the study was a loss of experience-dependent plasticity in the
      place fields of old rats. During the first lap around the track on each day, the
      initial sizes of the place fields were the same between ages; however, place
      fields of young rats, but not old, expanded significantly during the first few
      laps around the track in a given recording session. As the place fields expanded,
      the rate of change of firing with phase slowed accordingly, so that the net phase
      change remained constant. Thus changes in field size and phase precession are
      coupled. A deficit in plasticity of place fields in old rats may lead to a less
      accurate population code for spatial location.

PMID- 9254689
TI  - Cellular-synaptic generation of sleep spindles, spike-and-wave discharges, and
      evoked thalamocortical responses in the neocortex of the rat.
AB  - Thalamocortical neuronal oscillations underlie various field potentials that are
      expressed in the neocortex, including sleep spindles and high voltage spike-and
      wave patterns (HVSs). The mechanism of extracellular current generation in the
      neocortex was studied in the anesthetized and awake rat. Field potentials and
      unit activity were recorded simultaneously along trajectories perpendicular to
      the cortical layers at spatial intervals of 100 microm by multiple-site recording
      silicon probes. Current source density (CSD) analysis revealed that the spatial
      positions of sinks in layers IV, V-VI, and II-III and of the accompanying sources
      were similar during sleep spindles, HVSs, and thalamic-evoked responses, although
      their relative strengths and timings differed. The magnitude and relative timing
      of the multiple pairs of sinks and sources determined the amplitude variability
      of HVSs and sleep spindles. The presence of temporally shifted dipoles was also
      supported by the time distribution of unit discharges in different layers.
      Putative interneurons discharged with repetitive bursts of 300-500 Hz. The spike
      component of HVSs was associated with fast field oscillations (400-600 Hz
      "ripples"). Discharges of pyramidal cells were phase-locked to the ripples. These
      findings indicate that the major extracellular currents underlying sleep
      spindles, HVSs, and evoked responses result from activation of intracortical
      circuitries. We hypothesize that the fast field ripples reflect summed IPSPs in
      pyramidal cells resulting from the high frequency barrage of interneurons.

PMID- 9254690
TI  - Granule cell activation of complex-spiking neurons in dorsal cochlear nucleus.
AB  - Dorsal cochlear nucleus (DCN) principal cells receive, in addition to their well
      known auditory inputs, various nonauditory inputs via a cerebellar-like granule
      cell circuit located in the superficial layers of the DCN. Activation of this
      circuit (granule cell axons make excitatory synapses on the principal cells but
      also contact inhibitory interneurons that project to the principal cells)
      produces strong inhibition of the principal cells. Here we investigate the role
      of cartwheel cells, homologs of cerebellar Purkinje cells, in producing this
      inhibition. The responses of type IV units (one type of principal cells) and of
      cartwheel cells were recorded to ortho- and antidromic activation of the granule
      cells (i. e., by stimulation of their inputs from the somatosensory cuneate and
      spinal trigeminal nuclei and by direct stimulation of their parallel fiber
      axons). Cartwheel cells were identified on the basis of recording depth and
      complex action potential shape. A four-pulse facilitation paradigm (four pulses
      at 50 msec intervals) was used; this stimulus allows separation of the apparently
      simple inhibitory somatosensory response of type IV units into a three-component
      (inhibition-excitation-inhibition) response. As expected, cartwheel cells are
      excited by granule cell activation; the latencies and four-pulse amplitudes of
      these responses correspond to the properties of the second, long-latency
      inhibitory component of type IV responses. The source of the first, short-latency
      inhibitory response is still unknown. Nevertheless, these results show that
      cartwheel cells convey inhibitory polysensory information to DCN principal cells.

PMID- 9254691
TI  - The response of subthalamic nucleus neurons to dopamine receptor stimulation in a
      rodent model of Parkinson's disease.
AB  - Overactivity in the subthalamic nucleus (STN) is believed to contribute to the
      pathophysiology of Parkinson's disease. It is hypothesized that dopamine receptor
      agonists reduce neuronal output from the STN. The present study tests this
      hypothesis by using in vivo extracellular single unit recording techniques to
      measure neuronal activity in the STN of rats with 6-hydroxydopamine-induced
      lesions of the nigrostriatal pathway (a model of Parkinson's disease). As
      predicted, firing rates of STN neurons in lesioned rats were tonically elevated
      under basal conditions and were decreased by the nonselective dopamine receptor
      agonists apomorphine and L-3, 4-dihydroxyphenylalanine (L-DOPA). STN firing rates
      were also decreased by the D2 receptor agonist quinpirole when administered after
      the D1 receptor agonist (+/-)- 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8
      diol (SKF 38393). Results of the present study challenge the prediction that
      dopaminergic agonists reduce STN activity predominantly through actions at
      striatal dopamine D2 receptors. Firing rates of STN neurons were not altered by
      selective stimulation of D2 receptors and were increased by selective stimulation
      of D1 receptors. Moreover, there was a striking difference between the responses
      of the STN to D1/D2 receptor stimulation in the lesioned and intact rat;
      apomorphine inhibited STN firing in the lesioned rat and increased STN firing in
      the intact rat. These findings support the premise that therapeutic efficacy in
      the treatment of Parkinson's disease is associated with a decrease in the
      activity of the STN, but challenge assumptions about the roles of D1 and D2
      receptors in the regulation of neuronal activity of the STN in both the intact
      and dopamine-depleted states.

PMID- 9254692
TI  - An anatomical basis for visual calibration of the auditory space map in the barn
      owl's midbrain.
AB  - The map of auditory space in the external nucleus of the inferior colliculus
      (ICX) of the barn owl is calibrated by visual experience during development. ICX
      neurons are tuned for interaural time difference (ITD), the owl's primary cue for
      sound source azimuth, and are arranged into a map of ITD. When vision is altered
      by rearing owls with prismatic spectacles that shift the visual field in azimuth,
      ITD tuning in the ICX shifts adaptively. In contrast, ITD tuning remains
      unchanged in the lateral shell of the central nucleus of the inferior colliculus
      (ICCls), which provides the principal auditory input to the ICX, suggesting that
      the projection from the ICCls to the ICX is altered by prism-rearing. In this
      study, the topography of the ICCls-ICX projection was assessed in normal and
      prism-reared owls by retrograde labeling using biotinylated dextran amine. In
      juvenile owls at the age before prism attachment, and in normal adults, labeling
      patterns were consistent with a topographic projection, with each ICX site
      receiving input from a restricted region of the ICCls with similar ITD tuning. In
      prism-reared owls, labeling patterns were systematically altered: each ICX site
      received additional, abnormal input from a region of the ICCls where ITD tuning
      matched the shifted ITD tuning of the ICX neurons. These results indicate that
      anatomical reorganization of the ICCls-ICX projection contributes to the visual
      calibration of the ICX auditory space map.

PMID- 9254695
TI  - Effects of base mismatches on joining of short oligodeoxynucleotides by DNA
      ligases.
AB  - The requirement for Watson-Crick base pairing surrounding a nick in duplex DNA to
      be sealed by DNA ligase is the basis for oligonucleotide ligation assays that
      distinguish single base mutations in DNA targets. Experiments in a model system
      demonstrate that the minimum length of oligonucleotide that can be joined differs
      for different ligases. Thermus thermophilus (Tth) DNA ligase is unable to join
      any oligonucleotide of length six or less, while T4 DNA ligase and T7 DNA ligase
      are both able to join hexamers. The rate of oligonucleotide ligation by Tth DNA
      ligase increases between heptamer and nonamer. Mismatches which cause the duplex
      to be shortened by fraying, at the end distal to the join, slow the ligation
      reaction. In the case of Tth DNA ligase, mismatches at the seventh and eighth
      position 5'to the nick completely inhibit the ligation of octamers. The results
      are relevant to mechanisms of ligation.

PMID- 9254694
TI  - Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
AB  - The BLAST programs are widely used tools for searching protein and DNA databases
      for sequence similarities. For protein comparisons, a variety of definitional,
      algorithmic and statistical refinements described here permits the execution time
      of the BLAST programs to be decreased substantially while enhancing their
      sensitivity to weak similarities. A new criterion for triggering the extension of
      word hits, combined with a new heuristic for generating gapped alignments, yields
      a gapped BLAST program that runs at approximately three times the speed of the
      original. In addition, a method is introduced for automatically combining
      statistically significant alignments produced by BLAST into a position-specific
      score matrix, and searching the database using this matrix. The resulting
      Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the
      same speed per iteration as gapped BLAST, but in many cases is much more
      sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is
      used to uncover several new and interesting members of the BRCT superfamily.

PMID- 9254693
TI  - Homing endonucleases: keeping the house in order.
AB  - Homing endonucleases are rare-cutting enzymes encoded by introns and inteins.
      They have striking structural and functional properties that distinguish them
      from restriction enzymes. Nomenclature conventions analogous to those for
      restriction enzymes have been developed for the homing endonucleases. Recent
      progress in understanding the structure and function of the four families of
      homing enzymes is reviewed. Of particular interest are the first reported
      structures of homing endonucleases of the LAGLIDADG family. The exploitation of
      the homing enzymes in genome analysis and recombination research is also
      summarized. Finally, the evolution of homing endonucleases is considered, both at
      the structure-function level and in terms of their persistence in widely
      divergent biological systems.

PMID- 9254696
TI  - A prediction of the amino acids and structures involved in DNA recognition by
      type I DNA restriction and modification enzymes.
AB  - The S subunits of type I DNA restriction/modification enzymes are responsible for
      recognising the DNA target sequence for the enzyme. They contain two domains of
      approximately 150 amino acids, each of which is responsible for recognising one
      half of the bipartite asymmetric target. In the absence of any known tertiary
      structure for type I enzymes or recognisable DNA recognition motifs in the highly
      variable amino acid sequences of the S subunits, it has previously not been
      possible to predict which amino acids are responsible for sequence recognition.
      Using a combination of sequence alignment and secondary structure prediction
      methods to analyse the sequences of S subunits, we predict that all of the 51
      known target recognition domains (TRDs) have the same tertiary structure.
      Furthermore, this structure is similar to the structure of the TRD of the C5
      cytosine methyltransferase, Hha I, which recognises its DNA target via
      interactions with two short polypeptide loops and a beta strand. Our results
      predict the location of these sequence recognition structures within the TRDs of
      all type I S subunits.

PMID- 9254697
TI  - Precise assessment of microsatellite instability using high resolution
      fluorescent microsatellite analysis.
AB  - The instability of microsatellite sequences dispersed in the genome has been
      linked to a deficiency in cellular mismatch repair. This phenotype has been
      frequently observed in various human neoplasms and is regarded as a major factor
      in tumorigenesis. To demonstrate alterations in microsatellite sequences,
      polymerase chain reaction (PCR) and electrophoretic analysis are techniques often
      used. However, the electrophoretic profiles of PCR-amplified microsatellite
      sequences have not been well characterized. Moreover, the conventional method
      using autoradiography has critical problems in detection characteristics and
      migration accuracy. We made use of fluorescence-labeled PCR and laser scanning
      with linear detection characteristics, so as to detect bands quantitatively.
      Next, we characterized Taq polymerase-dependent modification of the amplified
      microsatellite sequences, using artificially synthesized microsatellite alleles
      and we optimized the electrophoretic profiles by enzymatic modification with T4
      DNA polymerase. We developed a dual fluorescence co-electrophoresis system, in
      which both samples derived from cancer and normal tissues are electrophoresed in
      the same lane, in order to minimize migration errors. These improvements
      remarkably facilitate precise and objective assessments of microsatellite
      instability. Analyzing many positive cases in cell lines and tissue specimens, we
      classified all the patterns of microsatellite alteration and set up new criteria
      for assessing microsatellite instability.

PMID- 9254698
TI  - Evidence for a hydroxide ion bridging two magnesium ions at the active site of
      the hammerhead ribozyme.
AB  - In the presence of magnesium ions, cleavage by the hammerhead ribozyme RNA at a
      specific residue leads to 2'3'-cyclic phosphate and 5'-OH extremities. In the
      cleavage reaction an activated ribose 2'-hydroxyl group attacks its attached 3'
      phosphate. Molecular dynamics simulations of the crystal structure of the
      hammerhead ribozyme, obtained after flash-freezing of crystals under conditions
      where the ribozyme is active, provide evidence that a mu-bridging OH-ion is
      located between two Mg2+ions close to the cleavable phosphate. Constrained
      simulations show further that a flip from the C3'- endo to the C2'- endo
      conformation of the ribose at the cleavable phosphate brings the 2'-hydroxyl in
      proximity to both the attacked phosphorous atom and the mu-bridging OH-ion. Thus,
      the simulations lead to a detailed new insight into the mechanism of hammerhead
      ribozyme cleavage where a mu-hydroxo bridged magnesium cluster, located on the
      deep groove side, provides an OH-ion that is able to activate the 2'-hydroxyl
      nucleophile after a minor and localized conformational change in the RNA.

PMID- 9254699
TI  - Peg5/Neuronatin is an imprinted gene located on sub-distal chromosome 2 in the
      mouse.
AB  - We have established a systematic screen for imprinted genes using a subtraction
      hybridization method with day 8.5 fertilized and parthenogenetic embryos. Two
      novel imprinted genes, Peg1/Mest and Peg3, were identified previously by this
      method, along with the two known imprinted genes, Igf2 and Snrpn. Recently three
      additional candidate imprinted genes, Peg5-7 , were detected and Peg5 is analyzed
      further in this study. The cDNA sequence of Peg5 is identical to Neuronatin, a
      gene recently reported to be expressed mainly in the brain. Two novel spliced
      forms were detected with some additional sequence in the middle of the known
      Neuronatin sequences. All alternatively spliced forms of Peg5 were expressed only
      from the paternal allele, confirmed using DNA polymorphism in a subinterspecific
      cross. Peg5/Neuronatin maps to sub-distal Chr 2, proximal to the previously
      established imprinted region where imprinted genes cause abnormal shape and
      behavior in neonates.

PMID- 9254700
TI  - Sce3, a suppressor of the Schizosaccharomyces pombe septation mutant cdc11,
      encodes a putative RNA-binding protein.
AB  - In the fission yeast Schizosaccharomyces pombe, the cdc11 gene is required for
      the initiation of septum formation at the end of mitosis. The sce3 gene was
      cloned as a multi-copy suppressor of the heat-sensitive mutant cdc11-136. When
      over-expressed, it rescues all mutants of cdc11 and also a heat-sensitive allele
      of cdc14, but not the cdc14 null mutant. Deletion shows that sce3 is not
      essential for cell proliferation. It encodes a putative RNA-binding protein which
      shows homology to human eIF4B. Immunolocalisation indicates that Sce3p is located
      predominantly in the cytoplasm. Elevated expression of sce3 increases the steady
      state level of cdc14 mRNA. Possible mechanisms of its action are discussed.

PMID- 9254701
TI  - Sequence-specific targeting and covalent modification of human genomic DNA.
AB  - We compare two techniques which enable selective, nucleotide-specific covalent
      modification of human genomic DNA, as assayed by quantitative ligation- mediated
      PCR. In the first, a purine motif triplex-forming oligonucleotide with a
      terminally appended chlorambucil was shown to label a target guanine residue
      adjacent to its binding site in 80% efficiency at 0.5 microM. Efficiency was
      higher in the presence of the triplex-stabilizing intercalator coralyne. In the
      second method, an oligonucleotide targeting a site containing all four bases and
      bearing chlorambucil on an interior base was shown to efficiently react with a
      specific nucleotide in the target sequence. The targeted sequence in these cases
      was in the DQbeta1*0302 allele of the MHC II locus.

PMID- 9254702
TI  - Inhibition of transcription by the TAR RNA of HIV-1 in a nuclear extract of HeLa
      cells.
AB  - Regulation of transcription of human immunodeficiency virus type-1 (HIV-1)
      requires specific interaction of Tat protein with the trans-activation response
      region (TAR). Inhibition of replication of HIV-1 has previously been achieved
      with a TAR decoy, namely a short RNA oligonucleotide that corresponded to the
      sequence of the authentic TAR RNA. Since TAR RNA has the potential to interact
      with cellular factors, we examined the effect of TAR RNA on efficiency of
      transcription in nuclear of HeLa cell extracts. We performed an in vitro
      transcription assay in the presence of authentic TAR RNA using a template that
      was driven by the CMV (cytomegalovirus) early promoter in a HeLa nuclear extract
      and found, for the first time, that TAR RNA inhibited transcription by
      approximately 60-70% independently of the Tat-TAR interaction. Furthermore, we
      evaluated inhibition of transcription by variants of TAR RNA and found that the
      TAR RNA loop, bases surrounding the loop, the triple base bulge and the 'lower'
      stem region of TAR RNA were responsible for the inhibition of transcription.
      Taken together, earlier reports on proteins that bind to TAR RNA and the present
      results suggest that integrity of TAR RNA is important for efficient binding to
      cellular transcription factors. As judged from the significant inhibition
      observed in this study, the TAR decoy might sequester transcription factors and
      thus it might potentially be able to inhibit transcription of housekeeping genes
      that are unrelated to Tat function.

PMID- 9254703
TI  - Cleavage of collagen RNA transcripts by hammerhead ribozymes in vitro is mutation
      specific and shows competitive binding effects.
AB  - We report here the in vitro use of hammerhead ribozymes as an approach to the
      gene therapy of osteogenesis imperfecta (OI). Our strategy for the treatment of
      this dominant genetic disorder is based on selective reduction of the level of
      the mRNA transcripts from the mutant allele. We studied the in vitro cleavage
      activity of five different hammerhead ribozymes targeted against synthetic
      transcripts of two naturally occurring human collagen mutations and against a
      point mutation introduced into a construct containing a portion of the mouse
      COL1A1 gene. This is the first demonstration that ribozyme cleavage is absolutely
      dependent on the presence of the ribozyme cleavage site introduced by the disease
      causing mutation. Cleavage specificity and activity were unchanged when the
      cleavage site was located in transcripts of progressively longer length. Cleavage
      efficiency depended directly on the ratio of ribozyme/substrate, as well as on
      the time and temperature of incubation. We investigated the competitive effects
      of both total RNA and normal synthetic transcripts on ribozyme cleavage activity.
      The ribozyme was able to localize and cleave its specific target even in the
      presence of a vast excess of total RNA. However, cleavage efficiency was linearly
      inhibited by the presence of a non- cleavable competitor substrate which
      contained a ribozyme binding site identical to the site present in the cleavable
      target. Although this competition could be eliminated by introducing a mismatch
      into one ribozyme binding arm, the presence of the mismatch decreased ribozyme
      cleavage efficiency. The mutation- specificity of ribozyme cleavage demonstrated
      in this work provides support for in vivo studies aimed at ribozyme development
      as a treatment for dominant negative genetic disorders.

PMID- 9254704
TI  - Recruitment of transcription factors to the target site by triplex-forming
      oligonucleotides.
AB  - Triplex-forming oligonucleotides (TFOs) are generally designed to inhibit
      transcription or DNA replication but can be used for more diverse purposes. Here
      we have designed a hairpin-TFO able to recruit transcription factors to a target
      DNA. The designed oligonucleotide contains a triplex-forming sequence, linked
      through a nucleotide loop to a double-stranded hairpin including the SRE enhancer
      of the c-fos gene promoter. We show here that this oligonucleotide can
      specifically recognise its DNA target at physiological salt and pH conditions.
      The stability of the triplex formed under these conditions is very high: >90% of
      the triplex remains intact after 24 h of incubation. Bound to the double-stranded
      target DNA, the oligonucleotide retains its ability to interact specifically with
      transcription factors, recruiting them to the proximity of the target DNA. Our
      results suggest that this type of oligonucleotide may prove useful in the design
      of new tools for artificial modulation of gene expression.

PMID- 9254705
TI  - Specific polyadenylation and purification of total messenger RNA from Escherichia
      coli.
AB  - Obtaining pure mRNA preparations from prokaryotes has been difficult, if not
      impossible, for want of a poly(A) tail on these messages. We have used poly(A)
      polymerase from yeast to effect specific polyadenylation of Escherichia coli
      polysomal mRNA in the presence of magnesium and manganese. The polyadenylated
      total mRNA, which could be subsequently purified by binding to and elution from
      oligo(dT) beads, had a size range of 0.4-4.0 kb. We have used hybridization to a
      specific plasmid-encoded gene to further confirm that the polyadenylated species
      represented mRNA. Withdrawal of Mg2+ from the polyadenylation reaction resulted
      in addition of poly(A) to 16S rRNA despite the presence of Mn2+, indicating the
      vital role of Mg2+ in maintaining the native structure of polysomes. Complete
      dissociation of polysomes into ribosomal subunits resulted in quantitative
      polyadenylation of both 16S and 23S rRNA species. Chromosomal lacZ gene-derived
      messages were quantitatively recovered in the oligo(dT)-bound fraction, as
      demonstrated by RT-PCR analysis. Potential advantages that accrue from the
      availability of pure total mRNA from prokaryotes is discussed.

PMID- 9254706
TI  - The RNase P RNA from cyanobacteria: short tandemly repeated repetitive (STRR)
      sequences are present within the RNase P RNA gene in heterocyst-forming
      cyanobacteria.
AB  - The RNase P RNA gene (rnpB) from 10 cyanobacteria has been characterized. These
      new RNAs, together with the previously available ones, provide a comprehensive
      data set of RNase P RNA from diverse cyanobacterial lineages. All heterocystous
      cyanobacteria, but none of the non-heterocystous strains analyzed, contain short
      tandemly repeated repetitive (STRR) sequences that increase the length of helix
      P12. Site-directed mutagenesis experiments indicate that the STRR sequences are
      not required for catalytic activity in vitro. STRR sequences seem to have
      recently and independently invaded the RNase P RNA genes in heterocyst-forming
      cyanobacteria because closely related strains contain unrelated STRR sequences.
      Most cyanobacteria RNase P RNAs lack the sequence GGU in the loop connecting
      helices P15 and P16 that has been established to interact with the 3'-end CCA in
      precursor tRNA substrates in other bacteria. This character is shared with
      plastid RNase P RNA. Helix P6 is longer than usual in most cyanobacteria as well
      as in plastid RNase P RNA.

PMID- 9254707
TI  - Nucleoprotein complex formation by the enhancer binding protein nifA.
AB  - The nitrogen fixation protein NifA is a member of the protein family activating
      transcription by the alternative eubacterial sigmaN (sigma54) RNA polymerase
      holoenzyme. Binding sites for NifA, upstream activator sequences (UASs), are
      remotely located. Interaction between holoenzyme bound in a closed promoter
      complex and NiFA is facilitated by bending of the intervening DNA by integration
      host factor (IHF). We have examined NifA contact with the Klebsiella pneumoniae
      nifH promoter UAS in the presence and absence of holoenzyme and IHF. Footprints
      with UV light were made on 5-BrdU-substituted DNA and DNase I and laser UV
      footprints on conventional DNA templates. Results establish that the consensus
      thymidine residues of the UAS motif 5'-TGT are in close proximity to NifA.
      Reactivity suggests that each UAS thymidine is not structurally equivalent.
      Titration of NifA binding to the UAS in the presence or absence of the closed
      promoter complex indicates that the interaction of NifA with the UAS is not
      strongly co-operative with holoenzyme or IHF, a result supportive of an
      activation mechanism not reliant upon simple recruitment of factors to the
      promoter. Laser footprints demonstrated that holoenzyme suppressed reactivity of
      promoter consensus -14, -15 and -16 T residues, indicating close contact. Binding
      of holoenzyme resulted in a specific increase in 5-BrdU reactivity at -9 within
      the holoenzyme binding site, likely reflecting DNA distortion. Enhanced -9
      reactivity required sigmaNN-terminal sequences that are necessary for activation.
      Since T-9 is melted in open complexes the closed complex appears poised for
      melting. Open promoter complex formation was accompanied by a distinct change in
      laser footprint signal at -11, consistent with the view that nucleation of strand
      separation occurs within or close to the -12 promoter element.

PMID- 9254708
TI  - The binding of two dimers of IciA protein to the dnaA promoter 1P element
      enhances the binding of RNA polymerase to the dnaA promoter 1P.
AB  - Transcription of the dnaA gene from the promoter 1P has been shown to be
      activated in vitro and in vivo by the binding of IciA protein to two sites on the
      dnaA promoter region [Lee, Y. S., Kim, H., and Hwang, D. S. (1996) Mol. Microbiol
      . 19, 389-396; Lee, Y. S., and Hwang, D. S. (1997) J. Biol. Chem. 272, 83-88]. In
      vitro transcription assays using DNA fragments carrying variable combinations of
      two IciA binding sites revealed that IciA binding site I (IciA I site), which is
      located upstream of the promoter 1P, is responsible for the transcriptional
      activation. Binding of one dimeric IciA protein to the IciA I site is followed by
      binding of the second dimer. Two dimers of IciA protein, rather than one dimer,
      on the IciA I site appeared to enhance the binding of RNA polymerase to the
      promoter 1P, resulting in the activation of transcription from the promoter 1P.

PMID- 9254709
TI  - Contacts between Bacillus subtilis catabolite regulatory protein CcpA and amyO
      target site.
AB  - Catabolite control protein A (CcpA) is a global regulatory protein involved in
      catabolite repression and glucose activation in Gram-positive bacteria. cis 
      Acting DNA sequences, catabolite response elements ( cre s), involved in this
      regulatory system contain a 14 base pair (bp) region of dyad symmetry. CcpA, a
      repressor of the Lac I family, has been shown to bind specifically to cre s. To
      better understand cre recognition by CcpA, we have focused on the interaction
      between CcpA and the amyE cre , called amyO, which is located at the
      transcription start site of the alpha-amylase gene. DNA-protein complexes were
      probed with dimethylsulfate (DMS) and N -ethylnitrosourea (EtNU) to identify
      guanines and phosphates that participate in complex formation. Interaction
      between amyO and CcpA visualized through methylation protection and interference
      showed that CcpA contacts guanine residues at the outer bounds of amyO with
      higher affinity than near the dyad axis. From ethylation interference studies, it
      was found that CcpA contacts three phosphate groups at each end of amyO, and one
      or two phosphate groups near the dyad axis. Exonuclease III protection revealed
      that CcpA protects a 26 bp region centered around the dyad axis of amyO. The
      isolated N-terminal fragment still specifically bound to the sequence resembling
      the half sites of the amyO sequence. Considering these findings and the helical
      structure of B-DNA, our results suggest that each of the two monomers of the CcpA
      molecule contact the major groove in each half of the region of dyad symmetry and
      that the contacts are on the same face of the DNA helix, which is typical of
      bacterial repressor-operator interactions. However, the absence of strong
      contacts near the dyad axis by CcpA is in contrast to the situation with the gal
      repressor, another member of the Lac I family of repressors.

PMID- 9254710
TI  - Effects of diaminopurine and inosine substitutions on A-tract induced DNA
      curvature. Importance of the 3'-A-tract junction.
AB  - Gel migration and uranyl photoprobing have been used to study the effects of
      inosine and 2,6-diaminopurine (2,6-DAP) substitution on adenine-tract (A-tract)
      induced DNA curvature. Using a 10mer repeated sequence including five inosines we
      show by uranyl photoprobing that a narrow minor groove varying in phase with the
      helix repeat is not the cause of DNA curvature. Further, we have systematically
      studied by gel migration the effects on A-tract induced curvature of either
      single or full substitution with inosine and/or 2,6-DAP in a 5'-AAAAAGCCGC
      3'sequence. DNA curvature is shown to increase when inosines are substituted for
      the guanosines in the sequence between the A-tracts. By comparing the effects of
      each monosubstitution it can be seen that when the G closest to the 3'-end of the
      A-tract is substituted the effect on DNA curvature is much stronger than when
      substitution is made at any other position. By contrast, curvature is abolished
      when 2,6-DAP residues are substituted for all adenines, and monosubstitution
      reveals that the effect of substituting a single adenine is strongest at the 3'
      end of the A-tract. These results favor a model in which the curvature induced by
      an A-tract in DNA molecules is primarily located at the junction with the 3'-end
      of the A-tract, and this peculiar junction is created because the A-tract has a
      preference to form a non-B-DNA structure which builds up from the 5'-end.

PMID- 9254711
TI  - Expression of bovine mitochondrial tRNASer GCU derivatives in Escherichia coli.
AB  - By replacing a stretch of five A-U base pairs in the acceptor stem with G-C
      pairs, mitochondrial tRNA-SerGCU lacking a D arm could be expressed in
      Escherichia coli cells in considerable amounts. The expressed tRNA with no
      modified nucleoside was serylated in vitro with the mitochondrial enzyme. The
      tRNASerGCU derivatives carrying identity elements for alanine tRNA and the
      related anticodons were expressed. However, this expression event did not affect
      cell growth, probably because the expression started from the late log phase,
      which suggests that these mitochondrial tRNA derivatives are not involved in
      E.coli gene expression systems. Although there are some restrictions in the
      secondary structure of tRNAs that can be expressed by this method, it could prove
      useful for preparing large amounts of heterologous tRNAs in vivo.

PMID- 9254712
TI  - Antisense oligonucleotide binding to U5 snRNP induces a conformational change
      that exposes the conserved loop of U5 snRNA.
AB  - Conformational rearrangements of the spliceosomal small nuclear RNAs (U snRNAs)
      are essential for proper assembly of the active site prior to the first catalytic
      step of splicing. We have previously shown that conformational changes caused by
      binding of an antisense 2'-O-methyl RNA oligonucleotide (BU5Ae) to U5 snRNA nt 68
      88 disrupted the U4/U5/U6 complex and induced formation of the U1/U4/U5 and U2/U6
      complexes. Here we show that the conformational change induced by BU5Ae exposes
      the invariant loop of U5 that binds the 5'exon and also reorganizes internal loop
      1 (IL1) and the top of stem 2. Interestingly, we have also previously found that
      the U1/U4/U5 complex induced by BU5Ae brings the invariant loop of U5 into close
      proximity with the 5'-end of U1. Taken together, these data suggest that U1 and
      U5 may both contribute to the ability of the U1/U4/U5 complex to bind the 5'
      splice site.

PMID- 9254713
TI  - ESSA: an integrated and interactive computer tool for analysing RNA secondary
      structure.
AB  - With ESSA, we propose an approach of RNA secondary structure analysis based on
      extensive viewing within a friendly graphical interface. This computer program is
      organized around the display of folding models produced by two complementary
      methods suitable to draw long RNA molecules. Any feature of interest can be
      managed directly on the display and highlighted by a rich combination of colours
      and symbols with emphasis given to structural probe accessibilities. ESSA also
      includes a word searching procedure allowing easy visual identification of
      structural features even complex and degenerated. Analysis functions make it
      possible to calculate the thermodynamic stability of any part of a folding using
      several models and compare homologous aligned RNA both in primary and secondary
      structure. The predictive capacities of ESSA which brings together the
      experimental, thermodynamic and comparative methods, are increased by coupling it
      with a program dedicated to RNA folding prediction based on constraints
      management and propagation. The potentialities of ESSA are illustrated by the
      identification of a possible tertiary motif in the LSU rRNA and the visualization
      of a pseudoknot in S15 mRNA.

PMID- 9254714
TI  - Competition between HMG-I(Y), HMG-1 and histone H1 on four-way junction DNA.
AB  - High mobility group proteins HMG-I(Y) and HMG-1, as well as histone H1, all share
      the common property of binding to four-way junction DNA (4H), a synthetic
      substrate commonly used to study proteins involved in recognizing and resolving
      Holliday-type junctions formed during in vivo genetic recombination events. The
      structure of 4H has also been hypothesized to mimic the DNA crossovers occurring
      at, or near, the entrance and exit sites on the nucleosome. Furthermore, upon
      binding to either duplex DNA or chromatin, all three of these nuclear proteins
      share the ability to significantly alter the structure of bound substrates. In
      order to further elucidate their substrate binding abilities, electrophoretic
      mobility shift assays were employed to investigate the relative binding
      capabilities of HMG-I(Y), HMG-1 and H1 to 4H in vitro. Data indicate a definite
      hierarchy of binding preference by these proteins for 4H, with HMG-I(Y) having
      the highest affinity (Kd approximately 6.5 nM) when compared with either H1 (Kd
      approximately 16 nM) or HMG-1 (Kd approximately 80 nM). Competition/titration
      assays demonstrated that all three proteins bind most tightly to the same site on
      4H. Hydroxyl radical footprinting identified the strongest site for binding of
      HMG-I(Y), and presumably for the other proteins as well, to be at the center of
      4H. Together these in vitro results demonstrate that HMG-I(Y) and H1 are co
      dominant over HMG-1 for binding to the central crossover region of 4H and suggest
      that in vivo both of these proteins may exert a dominant effect over HMG-1 in
      recognizing and binding to altered DNA structures, such as Holliday junctions,
      that have conformations similar to 4H.

PMID- 9254715
TI  - Diversity among the primate eosinophil-derived neurotoxin genes: a specific C
      terminal sequence is necessary for enhanced ribonuclease activity.
AB  - The human eosinophil-derived neurotoxin (hEDN) is a secretory effector protein
      from eosinophilic leukocytes that is a member of the ribonuclease A (RNase A)
      family of ribonucleases. EDN is a rapidly evolving protein, accumulating non
      silent mutations at a rate exceeding those of most other functional coding
      sequences studied in primates. Although all primate EDNs retain the structural
      and functional residues known to be prerequisites for ribonuclease activity, we
      have shown previously that recombinant EDN derived from a New World monkey
      sequence ( Saguinus oedipus ) had significantly less catalytic activity than the
      human (hEDN) ortholog.In this work, we have prepared recombinant proteins from
      EDN from sequences derived from orangutan (Pongo pygmaeus, oEDN) and Old World
      monkey (Macaca fascicularis, mcEDN) genomic DNAs, and from a second New World
      monkey sequence (Aotus trivirgatus, omEDN) as well. The catalytic efficiencies [
      k cat/ K m (M-1s-1)] determined for both oEDN and mcEDN were similar to that
      determined previously for hEDN, while omEDN displayed approximately 100-fold less
      catalytic activity. The relative ribonuclease activities of hEDN/omEDN chimeras
      pointed to a C-terminal segment as crucial to the enhanced catalytic activity
      hEDN, and substitution of Arg 132-Ile 133 of hEDN with the Thr-Thr pair at the
      analogous position in omEDN resulted in an approximately 10-fold reduction in
      hEDN's catalytic efficiency. However, the reverse substitution, Arg-Ile for Thr
      Thr in omEDN, did not enhance the catalytic efficiency of this relatively
      inactive protein. These results indicate that the Arg and/or Ile residues
      adjacent to the C-terminus are necessary (but not sufficient) for enhanced
      ribonuclease activity among the primate EDNs, and will permit prediction of the
      relative ribonuclease activities based on differences in primary structure.

PMID- 9254716
TI  - Re-usable DNA template for the polymerase chain reaction.
AB  - DNA covalently bound to an uncharged nylon membrane was used for consecutive
      amplifications of several different genes by PCR. Successful PCR amplifications
      were obtained for membrane-bound genomic and plasmid DNA. Membrane-bound genomic
      DNA templates were re-used at least 15 times for PCR with specific amplification
      of the desired gene each time. PCR amplifications of specific sequences of p53,
      p16, CYP1A1, CYP2D6, GSTM1 and GSTM3 were performed independently on the same
      strips of uncharged nylon membrane containing genomic DNA. PCR products were
      subjected to restriction fragment length polymorphism analysis, single-strand
      conformational polymorphism analysis and/or dideoxy sequencing to confirm PCR
      amplified gene sequences. We found that PCR fragments obtained by amplification
      from bound genomic DNA as template were identical in sequence to those of PCR
      products obtained from free genomic DNA in solution. PCR was performed using as
      little as 5 ng genomic or 4 fg plasmid DNA bound to membrane. These results
      suggest that DNA covalently bound to membrane can be re-used for sample-specific
      PCR amplifications, providing a potentially unlimited source of DNA for PCR.

PMID- 9254718
TI  - A solid-phase assay to screen monoclonal antibodies against DNA-binding protein.
AB  - A method is described for selecting monoclonal antibodies (mAb) against DNA
      binding protein. The protocol involves a non-radioactive solid-phase DNA binding
      assay using a 96-well plate. Because the solid-phase assay is highly specific and
      sensitive, partially purified antigen is sufficient for the immunization, and mAb
      screening can be performed with crude cell extract as the antigen. MAbs obtained
      by this method could supershift the DNA-protein complex in the electromobility
      shift assay, and were sufficient for immunoscreening of a cDNA expression
      library.

PMID- 9254717
TI  - pH dependence of self-splicing by the group IA2 intron in a pre-mRNA derived from
      the nrdB gene of bacteriophage T4.
AB  - The nrdB gene of bacteriophage T4 contains a group IA2 intron. We have
      investigated the kinetics of self-splicing by a shortened variant of nrdB pre
      mRNA in the presence of the co-substrates guanosine and 2'-amino-2'
      deoxyguanosine. The pH dependence of the first transesterification step displayed
      parallel linear correlations for the two different co-substrates up to pH 7,
      above which the reaction with guanosine levels off to become pH independent. The
      plot for the 30-fold slower reaction with 2'-aminoguanosine is linear up to pH 8
      8.5 and then levels off. The linear correlations with slopes close to unity
      suggest that a deprotonation event accelerates the transesterification reaction
      and that a change in rate limiting step occurs at a first order rate constant of
      approximately 1 min-1(i.e. for our system k cat/ K m approximately 10(5) M-1 min
      1). The pH dependence of observed rate constants in different divalent metal ion
      mixtures, where the 2'-aminoguanosine-dependent reaction is enhanced 6- and 35
      fold compared with that in magnesium, strongly supports this conclusion. This is,
      to our knowledge, the first report on an intact self-splicing group I intron
      where use of different co-substrates and divalent metal ions shows that a
      deprotonation enhances the rate and verifies that the transitions occurring
      during splicing of group I introns are all part of a common reaction sequence.

PMID- 9254719
TI  - Rapid determination of the complexity of cDNA bands extracted from DDRT-PCR
      polyacrylamide gels.
AB  - A band extracted from a differential display polyacrylamide gel often represents
      a composite of heterogeneous products. We have developed a non- radioactive
      method to simply and rapidly analyse its complexity. A fluorescent restriction
      enzyme fingerprint of the composite mixture is generated. The number of
      individual bands observed in this fingerprint indicates the complexity of the re
      amplified cDNA mixture. Restriction fingerprints of the inserts of cDNA subclones
      derived from the re-amplified cDNA mixture are compared to the composite
      fingerprint to select those representing the most intense bands in the composite.
      This dramatically reduces the number of clones required for further
      characterisation.

PMID- 9254720
TI  - Microamplification of specific chromosome sequences; an improved method for
      genome analysis.
AB  - An improved method was developed for microdissection and cloning of metaphase as
      well as pachytene chromosomes. The protocol incorporates efficient ligation of
      chromosomal DNA with linker adaptors, abolishment of microcloning steps and the
      reduction of micromanipulation. The threshold for amplifying genomic DNA template
      was in the range of 2-20 femtogram. The amplification products had a size
      distribution between 200 and 1300 bp (average 500 bp). Using pachytene
      chromosomes of maize the selectivity for segment-specific libraries can be
      increased between 10- and 20-fold. The approach described here is being applied
      to the fine mapping and isolation of genes conveying resistance against plant
      pathogens.

PMID- 9254721
TI  - Centromeric inactivation in a dicentric human Y;21 translocation chromosome.
AB  - A de novo dicentric Y;21 (q11.23;p11) translocation chromosome with one of its
      two centromeres inactive has provided the opportunity to study the relationship
      between centromeric inactivation, the organization of alphoid satellite DNA and
      the distribution of CENP-C. The proband, a male with minor features of Down's
      syndrome, had a major cell line with 45 chromosomes including a single copy of
      the translocation chromosome, and a minor one with 46 chromosomes including two
      copies of the translocation chromosome and hence effectively trisomic for the
      long arm of chromosome 21. Centromeric activity as defined by the primary
      constriction was variable: in most cells with a single copy of the Y;21
      chromosome, the Y centromere was inactive. In the cells with two copies, one copy
      had an active Y centromere (chromosome 21 centromere inactive) and the other had
      an inactive Y centromere (chromosome 21 centromere active). Three different
      partial deletions of the Y alphoid array were found in skin fibroblasts and one
      of these was also present in blood. Clones of single cell origin from fibroblast
      cultures were analysed both for their primary constriction and to characterise
      their alphoid array. The results indicate that (1) each clone showed a fixed
      pattern of centromeric activity; (2) the alphoid array size was stable within a
      clone; and (3) inactivation of the Y centromere was associated with both full
      sized and deleted alphoid arrays. Selected clones were analysed with antibodies
      to CENP-C, and staining was undetectable at both intact and deleted arrays of the
      inactive Y centromeres. Thus centromeric inactivation appears to be largely an
      epigenetic event.

PMID- 9254722
TI  - Rad51 immunocytology in rat and mouse spermatocytes and oocytes.
AB  - On the assumption that Rad51 protein plays a role in early meiotic chromosomal
      events, we examine the location and time of appearance of immuno-reactive Rad51
      protein in meiotic prophase chromosomes. The Rad51 foci in mouse spermatocytes
      appear after the emergence of, and attached to, short chromosomal core segments
      that we visualize with Cor1-specific antibody. These foci increase in number to
      about 250 per nucleus at the time when core formation is extensive. The numbers
      are higher in mouse oocytes and lower in rat spermatocytes, possibly correlating
      with recombination rates in those cases. In the male mouse, foci decrease in
      number to approximately 100 while chromosome synapsis is in progress. When
      synapsis is completed, the numbers of autosomal foci decline to near 0 while the
      X chromosome retains about 15 foci throughout this time. This stage coincides
      with the appearance of testis-specific histone H1t at mid- to late pachytene.
      Electron microscopy reveals that at first Rad51 immunogold-labeled 100 nm nodules
      are associated with single cores, and that they come to lie between the
      chromosome cores during synapsis. It appears that these nodules may be the
      homologs of the Rad51-positive early nodules that are well documented in plants.
      The reciprocal recombination-correlated late nodules appear after the Rad51 foci
      are no longer detectable. The absence of Rad51 foci in the chromatin loops
      suggests that in wild-type mice Rad51/DNA filaments are restricted to DNA at the
      cores/synaptonemal complexes. The expected association of Rad51 protein with
      Rad52 could not be verified immunocytologically.

PMID- 9254723
TI  - Constitutive and strong association of PAF53 with RNA polymerase I.
AB  - Mouse RNA polymerase I (Pol I) is composed of 14 polypeptides, 3 of which are
      thought to be loosely associated with, and may be dislodged from, Pol I. To find
      out whether these polymerase-associated factors (PAF53, 51, and 49) serve a role
      in growth-dependent control of rDNA transcription, we generated polyclonal
      antibodies against three subunits of murine Pol I, RPA116, RPA40 and PAF53, and
      used different experimental approaches, e.g. immunoblot analysis,
      immunoprecipitation and immunofluorescence studies, to compare the stoichiometry
      of individual subunits both in different Pol I preparations and in extracts from
      cells grown under different conditions. This comparative analysis reveals that
      the molar ratio of the second largest subunit RPA116 to PAF53 is the same,
      irrespective of whether crude extracts or highly purified Pol I fractions are
      analyzed. Significantly, the relative level of PAF53 was comparable in
      exponentially growing or growth-arrested cells, indicating that growth-dependent
      fluctuations in Pol I activity are not accompanied by alterations in the amount
      of PAF53. In addition, we show by high resolution immunofluorescence analysis
      that, under conditions of repressed rDNA transcription, including serum
      starvation, actinomycin treatment und during mitosis, PAF53 remains attached to
      the transcriptional machinery. The finding that the Mr 53,000 protein remains in
      the multiprotein complex under all experimental conditions tested indicates that
      PAF53 is not a loosely associated regulatory factor but a bona fide subunit of
      Pol I.

PMID- 9254724
TI  - Chromosome-specific alpha-satellite DNA from the centromere of chimpanzee
      chromosome 4.
AB  - The centromeric regions of human and primate chromosomes are characterized by
      diverged subsets of tandemly repeated alpha-satellite DNA. Comparison of the
      alpha-satellites on known homologous chromosomes in human and chimpanzee provides
      insight into the very rapid evolution of satellite DNA sequences and the
      mechanisms that shape complex genomes. By using oligonucleotide primers specific
      for a conserved region of human alpha-satellite DNA, we have amplified a
      chromosome-specific alpha-satellite subset from the chimpanzee genome by the
      polymerase chain reaction. Fluorescence in situ hybridization showed that clones
      palphaPTR4N and palphaPTR4H are homologous to sequences at the centromere of the
      chimpanzee chromosome 4. This alpha-satellite subset is organized as a series of
      pentameric (higher-order) repeats, operationally defined by digestion of genomic
      DNA with HaeIII, MboI, RsaI, SstI, and XbaI. The lengths of four independent
      centromeric arrays measured by pulsed-field gel electrophoresis varied between
      800 and 3,500 kb (mean = 1,850 kb, SD = 1,000 kb). Nucleotide sequence analysis
      demonstrated that chimpanzee chromosome 4 alpha-satellite is most closely related
      to the suprachromosomal subfamily II, which is evolutionarily different from the
      subfamily I to which the alpha-satellite on the homologous human chromosome 5
      belongs. This implies that the human-chimpanzee sequence divergence has not
      arisen from a common ancestral alpha-satellite repeat(s) but instead represents
      concerted evolution of distinct repeats on homologous chromosomes.

PMID- 9254725
TI  - The intranuclear organization of normal, hemizygous and excision-deficient rRNA
      genes during developmental amplification in Tetrahymena thermophila.
AB  - In the ciliated protozoan, Tetrahymena thermophila, the diploid germinal
      micronucleus contains two allelic copies of the gene for ribosomal RNA (rDNA).
      During genesis of new somatic macronuclei the germline rDNA gene is excised by
      developmentally programmed chromosome breakage and preferentially amplified to
      approximately 9, 000 copies. We have studied this process by fluorescence in situ
      hybridization. We find that initially rDNA amplification is restricted to two
      separate and highly confined regions of the nucleus. Analysis of nuclei that are
      hemizygous for the rDNA locus reveals that each focus of hybridization is derived
      from a single allele of the rDNA. As rDNA amplification progresses these two foci
      of hybridization disperse and spread throughout the macronucleus, eventually
      forming approximately 100-500 new nucleoli. These events are correlated with
      morphologically distinct developmental stages. We investigated the amplification
      of the C3 allele of the rDNA that confers a replication advantage over the B
      allele during vegetative propagation, and find no evidence for preferential
      amplification of the C3 early in rDNA maturation. We also show that the rmm 11
      rDNA mutant allele, which is defective for developmentally programmed rDNA
      excision, can be amplified during the two-foci stage in mutant homozygotes and
      heterozygotes, but fails to amplify further and disperse into multiple nucleoli.
      These data indicate that amplification of the rmm 11 allele is not delayed during
      the initial rounds of amplification, and suggest that efficient excision is not
      required for this amplification to occur. We propose that rDNA amplification is a
      two-step process. First, the two rDNA alleles are independently amplified, while
      allelic copies remain closely associated. Later, copies of the rDNA disperse and
      are further amplified, presumably because rDNA excision has occurred, generating
      fully mature rDNA minichromosomes that are able to replicate to high copy number.

PMID- 9254726
TI  - Hybrid origin of a B chromosome (PSR) in the parasitic wasp Nasonia vitripennis.
AB  - Little is known about the origin and evolution of supernumerary (B) chromosomes.
      This study utilizes molecular markers to examine the evolutionary history and
      microstructural organization of the supernumerary paternal-sex-ratio (PSR)
      chromosome of the parasitic wasp Nasonia vitripennis. Copies of the
      retrotransposon NATE were previously isolated from PSR and the genomes of N.
      vitripennis and related wasp species. A phylogenetic analysis of sequences
      representing 29 elements from PSR and seven wasp species, coupled with a
      hybridization analysis of elements in genomic DNA provides evidence that PSR was
      recently transferred into N. vitripennis from a species in the genus
      Trichomalopsis. A linear region of the PSR chromosome was compared by Southern
      blot analysis with genomic DNA from N. vitripennis, Nasonia longicornis,
      Trichomalopsis americanus, and Trichomalopsis dubius. A region organized
      similarly to the region on PSR was not evident in any of the species, thus a
      progenitor region was not identified. However, the hybridizations revealed that
      this region of PSR is primarily composed of repetitive sequences that appear
      dispersed in these wasp genomes, and might represent additional mobile elements.
      At least three different dispersed repeats are present in the 18 kb region of
      PSR. The abundance of tandem and dispersed repetitive sequences in this
      relatively small region provides additional evidence for the degenerate structure
      of the PSR chromosome.

PMID- 9254727
TI  - Integrated map of the Schizosaccharomyces pombe genome.
AB  - A restriction map of the entire Schizosaccharomyces pombe genome was constructed
      using two restriction enzymes (BamHI and PstI) that recognize 6 bp. The
      restriction map contains 420 minimally overlapping clones (miniset) and has 22
      gaps. We located 126 genes, marker fragments of DNA (NotI and SfiI linking
      clones), and 36 transposable elements by hybridization to unique restriction
      fragments.

PMID- 9254728
TI  - Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after
      treatment with gamma radiation and suramin.
AB  - Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing
      clinical trials in the treatment of hormone- and chemo-refractory tumors. Its
      unusual mechanism of action and its activity against prostate cancer raise the
      possibility that it could be particularly suitable for combined-modality
      treatment of prostate cancer. PC3 human prostate cancer cells were used as an in
      vitro model to test the possible interaction between suramin and ionizing
      radiation. Treatment with gamma radiation resulted in detachment of PC3 cells
      from the monolayer, and the detached cells exhibited internucleosomal DNA
      fragmentation characteristic of apoptosis. Low concentration of suramin (50-100
      micrograms/ml, 35-70 microM) increased spontaneous as well as radiation-enhanced
      apoptosis. However, suramin inhibited spontaneous and radiation-enhanced
      apoptosis at 300 micrograms/ml (210 microM), a concentration that is more
      commonly used in the clinic. At this concentration suramin inhibited DNA
      fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on
      inhibition of DNA fragmentation was reversible if the suramin was removed 24 h
      after irradiation. Despite inhibition of radiation-induced apoptosis by 300
      micrograms/ml suramin (from 5% to 2.9% at 48 h), clonogenic cell death was
      enhanced by the combination of suramin and radiation. The effects of radiation
      and suramin on clonogenic cell survival appeared to be additive by isobologram
      analysis at clinically relevant radiation doses. Continuous exposure to a lower
      concentration of suramin (100 micrograms/ml) during the clonogenic assay period
      was as effective in decreasing clonogenic survival as 48 h exposure to 300
      micrograms/ml suramin in decreasing clonogenic survival. Our data indicate that,
      when used in combination with radiation, suramin may be effective at
      concentrations that are lower than those required for efficacy as a single agent.

PMID- 9254729
TI  - Differential activation of p53 targets in cells treated with ultraviolet
      radiation that undergo both apoptosis and growth arrest.
AB  - The ability of p53 to act as a tumor suppressor is tightly correlated with its
      ability to function as a transcriptional activator at the G1/S-phase cell cycle
      checkpoint. Previous overexpression studies have indicated simultaneous induction
      of p53 target genes, despite opposing cellular functions of their protein
      products. To delineate the response of endoansactivation function to DNA damage
      in a normal cell, we irradiated early-passage rat embryo fibroblasts with 10 or
      50 J/m2 of ultraviolet light (mostly UV-C). We investigated the induction of p53
      targets and the response of the cells over 48 h. In this system, northern
      analysis revealed differential regulation of the p53 targets p21WAFI/CIPI, Mdm2,
      Ccng (also known as cyclin G) and Bax in accordance with their proposed functions
      in the cell. The growth suppressor p21WAFI/CIPI was activated initially (within 6
      h) after exposure to 10 J/m2, but not after 50 J/m2, in a p53-dependent manner.
      Both Ccng and Mdm2 were activated later than p21 (12-24 h) after exposure to 10
      J/m2. Expression of Bax was increased after exposure to both 10 J/m2 (24 h after
      UV exposure) and 50 J/m2 (6 h after UV exposure), which correlated well with the
      apoptosis seen in cells exposed to either dose. These fibroblasts also exhibited
      a temporary cell cycle arrest (< 8 h) at 10 J/m2. Thus we have investigated the
      physiological response of the p53 pathway in normal cells and identified a
      temporal order for induction of p53 targets. We demonstrate that both apoptosis
      and cell cycle arrest occur simultaneously when cells are treated with UV
      radiation, indicating that the amount of DNA damage is not the sole determinant
      of the cellular response.

PMID- 9254730
TI  - X-ray- and ultraviolet-radiation-induced mutations in Muta mouse.
AB  - To evaluate the usefulness of the transgenic Muta mouse for investigating
      radiation-induced mutations in vivo, we have examined the effects of whole-body X
      irradiation and compared them to the effects of ultraviolet light. The
      spontaneous mutation frequencies in young adults were about 7 x 10(-5) in the
      spleen, liver and skin. The mutation frequencies 1 week after a lethal dose of X
      radiation (8 Gy) were 3.2, 2.6 and 2.7 times the spontaneous levels in the
      spleen, liver and skin, respectively. When the skin was irradiated with 10 kJ m-2
      of UVB, the mutation frequency increased about 6 times. The mutation frequencies
      induced by an acute dose of 4 Gy or by a fractionated dose of 11.7 Gy (0.15 Gy x
      78 times, 3 times/week) in the spleen and liver were less than 2-fold the
      spontaneous levels at 16 weeks after irradiation. A comparison of X and UV
      radiation was also conducted with cultured cells derived from the mouse embryo.
      UVC of 5 J m-2 raised the mutation frequency to 15 times that of unirradiated
      cells, while 10 Gy X rays raised it 2.6 times. The findings indicate that the
      Muta mouse is less sensitive to X-ray-induced mutation than UV-induced mutation.

PMID- 9254731
TI  - Lack of uncoupling of S phase and mitosis after irradiation in p53- human
      lymphoblast cell lines.
AB  - It has been shown that p53- human colorectal cancer cells arrest after DNA damage
      in a G2-like state and may then undergo DNA synthesis without intervening mitosis
      (Waldman et al., Nature 381, 713-716, 1996). To further clarify the role of p53
      in the regulation of the G2/M-phase checkpoint, we have studied cells of three
      closely related human lymphoblastoid cell lines (TK6, WTK1 and TK6E6, an HPV16 E6
      transfected TK6 line) with differing p53 status. The cells were irradiated with
      1.5-12 Gy gamma rays with or without 2 mM caffeine. There was no evidence of
      uncoupling of DNA synthesis and mitosis after irradiation in the p53- cell lines,
      WTK1 and TK6E6, suggesting that this uncoupling may not be a universal
      phenomenon. The apparent formation of tetraploid cells after irradiation of cells
      of the p53- WTK1 line was due to the occurrence of a G2-phase block in a pre
      existing tetraploid population. These results support the conclusion that control
      of the G2/M-phase checkpoint after irradiation may differ among different cell
      types.

PMID- 9254732
TI  - Cumulative genetic damage in hematopoietic stem cells in a patient with a 40-year
      exposure to alpha particles emitted by thorium dioxide.
AB  - Thorotrast, a colloidal suspension of the long-lived radionuclide, thorium-232,
      was widely used as a radiographic contrast medium for several decades. Due to the
      poor excretion of the sol, however, Thorotrast would deposit in the liver, bone
      marrow and other tissue, and patients would receive alpha-particle irradiation
      for life. To gauge the cumulative genetic damage to hematopoietic stem cells due
      to chronic exposure to alpha particles, we conducted a multi-end-point evaluation
      in a 72-year-old man who had been administered a 32-ml bolus of Thorotrast during
      cerebral angiography performed over 40 years ago in 1950. Peripheral T
      lymphocytes were cultured to quantify the frequencies and cellular distributions
      of asymmetrical and symmetrical types of chromosome aberrations in first-division
      metaphases and micronuclei in cytokinesis-arrested interphase II cells.
      Aberrations were scored using classical chromosome group analysis methods and
      chromosome painting techniques. Assays of glycophorin-A (GPA) mutations in red
      blood cells were also performed to obtain a relative measurement of damage
      sustained by the erythroid stem cell population. Results revealed that
      approximately 30% of the lymphocytes in this patient contained one or more
      chromosome aberrations, the majority of which were of the "stable" type. About
      one-third of the lymphocytes with chromosome damage carried multiple aberrations,
      suggesting that significant numbers of stem cells survive exposures to alpha
      particle radiation that induce complex genomic alterations. Increased frequencies
      of GPA mutations were observed, demonstrating that genomic damage is also induced
      in erythroid progenitors. The numbers of micronuclei in lymphocytes were only
      moderately increased compared to expected values for persons of comparable age,
      and thus this end point was not useful for quantifying exposure level. Despite
      the relatively severe burden of somatic cell damage induced by 40 years of
      internal alpha-particle irradiation, the patient remains surprisingly free of any
      serious illness.

PMID- 9254733
TI  - Impaired cell proliferation in mice that persists across at least two generations
      after paternal irradiation.
AB  - Irradiation of male F0 mice 6 to 7 weeks prior to mating causes significant
      changes in the proliferation of F1 and F2 embryonic cells. These changes are
      revealed as a competitive cell proliferation disadvantage in chimera assays when
      the affected embryo is paired with a normal embryo in an aggregation chimera.
      This effect has been observed previously to be transmitted to F1 embryos for
      absorbed doses from 0.01 to 1.0 Gy; 0.01 Gy is about 100-fold lower than
      detectable using conventional germline mutation assays. However, until now there
      has been no reported cross-generation heritability. We now report that this
      competitive cell proliferation disadvantage persists without degradation in the
      F2 generation of embryos when F0 males received 1.0 Gy from gamma irradiation 6
      and 7 weeks prior to conception of F1 males.

PMID- 9254734
TI  - Incidence of primary malignancies other than breast cancer among women treated
      with radiation therapy for benign breast disease.
AB  - This report presents data on the long-term risks of developing malignancies other
      than breast cancer after exposure to scattered doses of ionizing radiation. The
      estimates were based on a cohort of 3,090 women who were diagnosed clinically
      with benign breast disease between 1925 and 1961. A total of 1,216 women were
      treated with radiation therapy. The breasts received a mean absorbed dose of 5.84
      Gy. Mean absorbed doses owing to scatter to 14 other organs were also determined.
      The lung received the highest mean scattered dose (0.75 Gy; range 0.004-8.98 Gy)
      and rectum the lowest (0.008 Gy; range 0-0.06 Gy). Median age at first exposure
      was 40 years. The follow-up lasted up to 61 years after treatment (mean follow-up
      27 years). End-point data were obtained from population-based registers. With
      internal reference the relative risk for non-breast solid tumors was 1.2 (95%
      confidence interval 1.0-1.5). However, this excess was not apparent when
      comparison with the general population was made (standardized incidence ratio =
      0.95; 95% confidence interval 0.84-1.07). Among individual sites no significantly
      increased risks were observed. For stomach cancer there was a linear increase
      with dose (ERR/Gy = 1.3; two-sided P = 0.05). No increased risk was observed for
      leukemias. In two earlier reports, breast cancer incidence has been shown to be
      significantly increased in this cohort of irradiated women. Our results suggest
      that the scattered doses from the breast irradiation may have increased the risk
      of cancers of other sites, but the small number of cases in different locations
      precludes strong interpretations.

PMID- 9254735
TI  - Intracranial tumors after radium treatment for skin hemangioma during infancy--a
      cohort and case-control study.
AB  - The risk of developing intracranial tumors was studied in a Swedish cohort of
      11,805 infants treated with 226Ra for hemangioma of the skin between 1930 and
      1965. The cohort was followed up in the Swedish Cancer Register during the years
      1958 through 1992, giving 402,958 person-years at risk. Forty-seven intracranial
      tumors developed in 46 individuals. The standardized incidence ratio (SIR) was
      1.80 (95% CI 1.32-2.39). An excess number of cases was found for many
      histopathological subgroups, although the excess was statistically significant
      only for gliomas (n = 23, SIR 1.89, 95% CI 1.20-2.83) and meningiomas (n = 8, SIR
      2.42, 95% CI 1.06-4.77). Absorbed doses to the brain have been calculated. The
      mean dose to the brain was only 7.2 cGy. The dose response was evaluated by
      Poisson regression methods. There was an excess of intracranial tumors in all
      dose categories, but no clear dose-response relationship could be seen for the
      data. This indicates that explanations other than irradiation may also be
      involved. The selection of the reference population has been studied and
      confirmed to be representative. For individuals treated before 7 months of age,
      however, the data could be fitted to both the linear and the linear-quadratic
      model. These results may indicate that the youngest infants may be more sensitive
      to ionizing radiation and that even very low doses to the brain may increase the
      risk for intracranial tumors.

PMID- 9254736
TI  - Response of mouse intestine after single and fractionated irradiation with
      accelerated carbon ions with a spread-out Bragg peak.
AB  - The responses of mouse intestine were examined after irradiation with accelerated
      carbon ions with a spread-out Bragg peak. The carbon-ion beam (135 MeV/nucleon),
      accelerated by the RIKEN ring cyclotron facility, was modulated to have a spread
      out Bragg peak (SOBP) 3 cm wide. In the SOBP the biological dose (relative
      physical dose x RBE) was designed in earlier studies to be flat at the 10%
      survival level of Chinese hamster V79 cells. The numbers of surviving crypt
      clonogenic cells after single and fractionated irradiation with the carbon-ion
      beam were obtained by a microcolony assay method. The composite single-dose
      survival curves for the crypt clonogenic cells were calculated and fitted by a
      linear-quadratic (LQ) model. An analysis with the LQ model for crypt clonogenic
      cells showed that the alpha coefficient increased along with increasing LET, and
      that the beta coefficient was relatively constant, even for high-LET radiations.
      The biological dose distributions for the crypt clonogenic cells at the 10%
      survival level were flat in the SOBP. The isoeffective design of the SOBP for the
      135 MeV/nucleon carbonion beam, based on biological data from a mammalian in
      vitro cell system, appears to be applicable to the response of murine intestinal
      tissue in vivo.

PMID- 9254737
TI  - Whole-body gamma irradiation modifies bile composition in the pig.
AB  - The effects of 6 Gy whole-body 60Co gamma irradiation on bile composition in pigs
      were studied to determine possible alterations in the quality of the bile, which
      may be a determining factor in diarrhea as well as nutrient malabsorption, which
      classically occurs after irradiation. The bile duct of pigs was catheterized to
      allow a total and continuous deviation of bile over several weeks, before and
      after irradiation. After measurement of the volume and sampling, bile was
      returned to the animal via a duodenal catheter. Bile samples were then analyzed
      for cholesterol, phospholipid and total bile acid content. Individual bile acids
      were quantified by HPLC analysis. Bile flow was significantly decreased during
      the first 24 h and after the fifth day postirradiation. Whereas cholesterol,
      phospholipid and total bile acid concentrations were not altered, profiles of
      individual bile acids were modified significantly as early as the first day
      postirradiation. Moreover, the change of these profiles with time was specific
      for each bile acid. Such modifications in bile acid profiles resulted in a change
      in the properties of the bile acid pool in an increased proportion of
      dihydroxylated bile acids known to interfere with gut functions, and it is
      reasonable to suggest that radiation-induced changes in bile acid profiles may be
      involved in radiation-induced gastrointestinal disorders.

PMID- 9254738
TI  - The generation of hydroxyl radicals in the reaction of molecular oxygen with
      polyphosphate complexes of ferrous ion.
AB  - The reaction of Fe2+ with molecular oxygen (autoxidation) was investigated in 20
      mM phosphate buffer (pH 7.4) at 37 degrees C using a fluorescent OH probe,
      coumarin-3-carboxylic acid. The autoxidation of unchelated Fe2+ produces OH
      radicals. Polyphosphatic chelators (pyrophosphate and tri- and tetrapoly
      phosphate) enhanced the generation of radicals. This effect was explained by an
      alteration of the reaction mechanism. The two-electron reduction of the oxygen
      molecule and the generation of hydrogen peroxide intermediates are the major
      reactions during Fe2+ autoxidation. The polyphosphatic complexes of ferrous ion
      reduce molecular oxygen and reactive oxygen intermediates by a one-electron
      mechanism. The chelation of ferrous ion increases the generation of the
      superoxide radical and production of OH during ferrous ion autoxidation and in
      the Fenton reaction. The results consider the ferrous ion-polyphosphate system as
      a convenient model for the generation of hydroxyl radical in biological systems.

PMID- 9254739
TI  - Radioprotection against the formation of DNA double-strand breaks in cellular DNA
      but not native cellular chromatin by the polyamine spermine.
AB  - The complexing of histones with DNA and the resulting condensation of chromatin
      protect mammalian cell DNA from radiation-induced strand breakage. In recent
      studies of SV40 DNA and minichromosomes, marked radioprotection was afforded by
      spermine through polyamine-induced compaction and aggregation (Newton et al.,
      Radiat. Res. 145, 776-780, 1996). To evaluate the contribution of polyamines to
      the radioprotection of cellular chromatin, intact V79 cells, nuclei (native
      chromatin) and chromatin that was partially or completely stripped of histones
      were treated with spermine or putrescine and gamma-irradiated while embedded in
      agarose plugs, and induction of double-strand breaks was determined by pulsed
      field gel electrophoresis. In the absence of added spermine, the order of
      radiosensitivity was: dehistonized chromatin (DNA loops anchored to the nuclear
      matrix) > chromatin depleted of histone H1 > chromatin partially depleted of
      histone H1 > native chromatin > intact cells. Spermine at concentrations below 1
      mM was without effect on strand breakage in any of the preparations, except for
      limited radioprotection of H1-depleted chromatin. Increasing radioprotection with
      increasing concentration (1-10 mM) was provided to dehistonized chromatin by
      spermine but not by putrescine, a polyamine that does not compact DNA or
      chromatin. Significant radioprotection by spermine was also found for H1-depleted
      relaxed chromatin at concentrations > or = 1 mM. In contrast, no radioprotection
      by spermine (up to 10 mM) was observed for any of the chromatin preparations
      containing all histones. These observations support the hypothesis proposed by
      Newton et al. that spermine protects DNA against radiation damage via polyamine
      induced compaction and aggregation. With removal of histone H1, the exposed
      chromatin develops the ability to be protected by spermine. However, the absence
      of radioprotection of native chromatin by spermine is consistent with a role for
      histones as the major radioprotectors of cellular DNA and the differential
      radiosensitivity of decondensed compared to condensed cellular chromatin
      resulting from the effects of factors other than polyamines.

PMID- 9254740
TI  - Shift in global AIDS focus.

PMID- 9254741
TI  - AIDS pioneer to set up centre in SA.

PMID- 9254742
TI  - Doctors and the TRC--confronting our past.

PMID- 9254743
TI  - How can it be...?

PMID- 9254744
TI  - The Red Cross Air Ambulance--flight of fancy or not?

PMID- 9254745
TI  - Variegate porphyria in South Africa, 1688-1996--new developments in an old
      disease.
AB  - Variegate porphyria, an autosomal dominant inherited trait resulting in decreased
      activity of protoporphyrinogen oxidase, the penultimate haem biosynthetic enzyme,
      is characterised clinically by photosensitive skin disease and a propensity to
      acute neurovisceral crises. The disease has an exceptionally high frequency in
      South Africa, owing to a founder effect. The specific mutation in the
      protoporphyrinogen oxidase gene sequence which represents this founder gene has
      been identified. Genetic diagnosis is therefore now possible in families in whom
      the gene defect is known. However, the exact nature and degree of activity of the
      porphyria can only be determined by detailed quantitative biochemical analysis of
      excreted porphyrins. The relative contributions of the acute attack and the skin
      disease to the total disease burden of patients with variegate porphyria is not
      static, and in South Africa there have been significant changes over the past 25
      years, with fewer patients presenting with acute attacks, leaving a greater
      proportion to present with skin disease or to remain asymptomatic with the
      diagnosis being made in the laboratory. The most common precipitating cause of
      the acute attack of VP is administration of porphyrinogenic drugs. Specific
      suppression of haem synthesis with intravenous haem arginate is the most useful
      treatment of a moderate or severe acute attack. Although cutaneous lesions are
      limited to the sun-exposed areas, management of the skin disease of VP remains
      inadequate.

PMID- 9254746
TI  - Primary liver cancer in two sisters in Holland with intermittent acute porphyria.
AB  - Two sisters living in Holland, with a niece now living in South Africa, were
      reported in 1958 to have inherited intermittent acute porphyria (IAP). In 1994
      both sisters died from primary liver cancer. Other reports have also noted an
      increased mortality from carcinoma of the liver in porphyrics. Porphyria
      variegata has a high prevalence in white and coloured South Africans, and it
      would be relatively easy to ascertain whether those who have inherited the gene
      for this disorder, in South Africa, have a higher than reported mortality from
      liver cancer. If they do, consideration should be given to ways to reduce their
      risk of developing and dying from this cancer.

PMID- 9254747
TI  - The molecular basis of South African genetic porphyria established at last!

PMID- 9254749
TI  - The influence of the full blood count on medical inpatient management.
AB  - AIM: This investigation studied the use of the full blood count (FBC) in a
      general medical inpatient ward at Groote Schuur Hospital. OBJECTIVES: To
      determine the relative frequency of the reasons for which FBCs were requested
      (clinically indicated v. routine) and how they influenced patient management.
      PATIENTS: One hundred and sixty-five consecutive general medical inpatients
      admitted to the ward between September and December 1993 were included. Each
      patient underwent an FBC and differential white cell count prior to entering the
      ward. DESIGN: After taking a history and examining the patient, the physician
      responsible for each of the 165 patients completed a questionnaire. OUTCOMES
      MEASURED: Physicians had to indicate whether the FBC was routine or clinically
      indicated and how the FBC result influenced their patient management. RESULTS: In
      67.9% of cases the FBC was considered to be clinically indicated, while in 32.1%
      of cases it was routine. Although it was felt that 76.4% of the clinically
      indicated tests influenced patient care, patient management was changed in only
      24.7% of cases. In the case of routine tests, care was influenced in only 2.0% of
      cases. CONCLUSION: Routine tests have a very low clinical yield. There is no
      substitute for good clinical judgement and the practice of routine tests must be
      reviewed, as much time, money and patient discomfort could be saved by the
      elimination of unnecessary investigations.

PMID- 9254748
TI  - Thyroid cancer in South Africa--an indicator of regional iodine deficiency.
AB  - OBJECTIVE: Because follicular thyroid cancers predominate in iodine deficient and
      papillary cancers predominate in iodine-replete populations, we have analysed
      national and regional (former Transvaal) incidences of these cancer types as a
      surrogate measure of the population iodine nutritional status in South Africa.
      DESIGN: Statistical analysis, by race and sex, of differentiated thyroid cancers
      reported to the South African National Cancer Registry (1988), and of the
      computerised histology records of the Department of Anatomical Pathology, SAIMR
      (January 1990 to June 1994; Transvaal data). MAIN OUTCOME MEASURES: Relative
      frequencies of the two cancer types nationally and geographically in the
      Transvaal region. MAIN RESULTS: Thyroid cancer was underdiagnosed in populations
      other than white. Nationally, follicular histology accounted for 55% of all
      differentiated primary thyroid cancers, and predominated especially in black
      women. Follicular morphology predominated in blacks resident in the rural regions
      of the former Transvaal (58%), while papillary histology predominated in urban
      areas (of present-day Gauteng), irrespective of race (78%; P = 0.003).
      CONCLUSION: The national predominance of follicular thyroid cancer indicates that
      significant iodine deficiency exists in the country as a whole. The observed
      urban-rural differences in prevalences of follicular and papillary cancer types
      suggest regional differences in the severity of iodine deficiency. There is a
      need for a formal survey of the population iodine nutritional status in South
      Africa.

PMID- 9254750
TI  - Development of a health programme in a peri-urban informal settlement in Besters,
      KwaZulu-Natal.
AB  - OBJECTIVES: The demographic, socio-economic and environmental status of the peri
      urban informal settlement of Besters and its inhabitants' health, welfare and
      disability profiles were investigated for the development of a community-based
      health intervention programme. STUDY DESIGN: A cross-sectional study using a
      structured household questionnaire assessed community health status in July 1991
      in order to identify specific health and development needs through focus group
      discussions and community consultations. A health and development programme was
      established during 1992. Community participation in this programme was then
      assessed by measurement of the components of the health and development
      programme, categorised as inputs (resources), processes (activities), outputs
      (effects) and outcomes. SETTING: Besters, an informal peri-urban settlement north
      of Durban, KwaZulu-Natal. SUBJECTS: Residents of Besters. RESULTS: The
      demographic, environmental and morbidity profiles of Besters were consistent with
      both South African and international studies of informal communities. Patterns of
      health service utilisation reflected inappropriate use of the tertiary hospital
      in the city centre, grossly fragmented patterns of utilisation--both for
      preventive and curative care and for antenatal and maternity services--and,
      finally, a discordance between community health needs and ability to pay for
      services. The interaction between input, process and output measures of community
      participation are discussed. CONCLUSION: Integration of health service provision
      with other infrastructural development, based on community perceptions, enhances
      health development and community participation. Important lessons emerged about
      the strengths and limitations of community participation and its relevance for
      other communities.

PMID- 9254752
TI  - Diagnosis of variegate porphyria at birth by demonstration of the R59W mutation.

PMID- 9254751
TI  - The Truth and Reconciliation Commission and post-traumatic stress disorder.

PMID- 9254754
TI  - Primary care--continuity v. segregation.

PMID- 9254755
TI  - Not the right middle lobe syndrome?

PMID- 9254756
TI  - Poor feedback from specialists.

PMID- 9254757
TI  - The high road to rural medicine.

PMID- 9254758
TI  - The high road to rural medicine.

PMID- 9254759
TI  - Total intravenous or inhalational anaesthesia--a cost comparison.

PMID- 9254760
TI  - Interpretation of HIV test results for insurance purposes.

PMID- 9254761
TI  - Sulpiride (Eglonyl)--use to stimulate lactation.

PMID- 9254763
TI  - Can cardiologists disregard cardiac genetics and molecular biology?

PMID- 9254762
TI  - Virodene--support misguided.

PMID- 9254764
TI  - Should all cardiac patients be offered the choice of cardiac rehabilitation?
AB  - OBJECTIVE: To determine whether cardiac rehabilitation services are beneficial to
      patients and cost-effective. DESIGN: Several recent publications are reviewed.
      The first of these, 'Cardiac Rehabilitation. Clinical Practice Guideline No. 17',
      is itself a review of original published research: 900 scientific reports were
      examined by a multidisciplinary panel and 334 of these were considered to be of
      sufficient scientific merit to be used as the references for the guideline. The
      other publications discussed are: The American Heart Association Consensus Panel
      Statement, 'Preventing heart attack and death in patients with coronary disease',
      the American College of Cardiology's recommendations on 'Matching the intensity
      of risk factor management with the hazard for coronary disease events' and
      Recommendations of the Task Force of the European Society of Cardiology, the
      European Atherosclerosis Society and European Society of Hypertension,
      'Prevention of coronary heart disease in clinical practice'. RESULTS: Cardiac
      rehabilitation brought about substantial benefits in risk factor profiles,
      including improvement in exercise tolerance, blood lipids, psychosocial well
      being, and reduction in cigarette smoking and stress levels. In addition there
      was well-documented proof of improvement of pathophysiological measures, such as
      relief of symptoms, less progression and greater regression of disease and a
      reduction in mortality. As an intervention, cardiac rehabilitation was shown to
      be as cost-effective as many pharmacological regimens and surgical interventions.
      CONCLUSIONS: The evidence in support of cardiac rehabilitation is so overwhelming
      that all patients should be educated about this form of treatment and have the
      ultimate choice of accepting or rejecting it.

PMID- 9254765
TI  - Selective catheter ablation of the slow atrioventricular nodal pathway for atrial
      fibrillation.
AB  - The slow AV nodal pathway was ablated selectively in a 62-year-old man with
      uncontrolled rapid atrial fibrillation. This resulted in a much slower
      ventricular response without the need for permanent pacing. The pathophysiology
      is discussed.

PMID- 9254766
TI  - Ischaemic preconditioning does not protect hypertrophied myocardium against
      ischaemia.
AB  - OBJECTIVES: Because ischaemic preconditioning elicits a potent endogenous
      protective mechanism against the development of myocardial infarction, it is
      important to explore its utilisation in clinical situations. The aim of this
      study was to examine whether the myocardium of rats with genetic hypertension
      could be protected by ischaemic preconditioning. METHODS: Male New Zealand
      genetically hypertensive rats (GH-Wistar-derived) and normotensive Wistar
      controls (WAG-Wistar-derived), aged 12 months, were used. Isolated perfused
      hearts were preconditioned by 3 periods of 5 minutes' global ischaemia,
      interspersed with 5 minutes' reperfusion, and subsequently subjected to 25
      minutes' global ischaemia, followed by 30 minutes' reperfusion. RESULTS: Heart
      and body mass were significantly higher in GH rats. Although the heart/body mass
      ratios of GH rats were higher than those of WAG rats, the difference was not
      significant. The reperfusion coronary flow pattern during the preconditioning
      protocol differed markedly between the 2 groups. Only normotensive WAG hearts
      demonstrated protective effects of preconditioning on post-ischaemic function and
      tissue creatine phosphate content, while the GH hearts could not be
      preconditioned. CONCLUSIONS: An explanation for the failure of preconditioning in
      GH hearts is not yet available. The data caution against implementation of
      preconditioning in patients with angina pectoris and left ventricular
      hypertrophy.

PMID- 9254767
TI  - Sydenham's chorea--analysis of 27 patients and a review of the literature.
AB  - The first documented epidemic of Sydenham's chorea was in 1418. In 1686 Thomas
      Sydenham was the first to describe the condition, but it was Richard Bright who
      in 1831 first made the association between chorea and rheumatic fever. Chorea is
      one of the major diagnostic criteria for rheumatic fever. Chorea is often
      considered a benign self-limiting condition. Little is known about the
      pathophysiological process. A link between the group A beta-haemolytic
      streptococcus through an antibody-mediated immune response targeting the basal
      ganglia has been described. Special investigations have been done to ascertain
      the pathophysiology, but none is of diagnostic value. The aims of this study were
      to analyse the clinical findings, the role of special investigations in the
      management and course of Sydenham's chorea and to review the literature. Data on
      27 patients were analysed. Special investigations in these patients can be
      divided into those necessary to assist in diagnosing acute rheumatic fever and
      those to exclude other causes that mimic chorea. None of these tests was helpful
      in diagnosing chorea due to other causes; neither did they influence the
      management of these patients. In conclusion, Sydenham's chorea remains a clinical
      diagnosis and extensive and expensive special investigations are seldom
      warranted.

PMID- 9254768
TI  - Ruptured idiopathic left ventricular false aneurysm of the free wall associated
      with Takayasu's arteritis in a young child.
AB  - The co-existence in a young child of long-standing Takayasu's arteritis, chronic
      myocarditis and a false aneurysm of the left ventricle raises the possibility
      that a common inflammatory process may have accounted for all three findings. The
      unique combination of pathology observed in this patient may provide further
      evidence that widens the spectrum of cardiac involvement associated with
      Takayasu's disease to include the myocardium.

PMID- 9254769
TI  - Pitfalls in coronary stenting. A review of current strategies.

PMID- 9254770
TI  - Cardiovascular disease in pregnancy--Part I. Round-table discussion.

PMID- 9254771
TI  - ELITE study raises losartan's profile in heart failure therapy debate.

PMID- 9254772
TI  - Is hospitalisation necessary for recent-onset atrial fibrillation?

PMID- 9254774
TI  - Potential influence of tea consumption on the development of cardiovascular
      disease.

PMID- 9254773
TI  - Benefits beyond lipid-lowering.

PMID- 9254775
TI  - EBCT scanner installed at Pretoria Heart Hospital.

PMID- 9254777
TI  - Medical aid proposals.

PMID- 9254778
TI  - Safe packaging in SA.

PMID- 9254779
TI  - Backstreet abortion in South Africa.

PMID- 9254780
TI  - Fragile X syndrome occurs in the South African black population.

PMID- 9254781
TI  - Organ transplantation policy--for whom does the bell toll?

PMID- 9254782
TI  - Organ transplantation--the other view.

PMID- 9254783
TI  - Vitamin D and its analogues and the prevention and treatment of osteoporosis.

PMID- 9254784
TI  - The meaning of professionalism in medicine.
AB  - The challenges facing the professions (and perhaps especially the medical
      profession) in the new South Africa are complex and far-reaching. Here an attempt
      is made to place these challenges in local, global and historical perspectives to
      facilitate a deeper understanding of their implications. A brief outline of
      forces influencing the social construction of health services is followed by some
      sociological and professional concepts of professionalism, and some reasons are
      provided for the public's concern about the image professionals have of
      themselves. The inadequacy of defensive responses by professions is emphasised
      and the need is outlined for introspection and deeper understanding of ethics,
      human rights and values in relation to medical practice.

PMID- 9254785
TI  - The epidemiology of incomplete abortion in South Africa. National Incomplete
      Abortion Reference Group.
AB  - OBJECTIVE: To describe the epidemiology of incomplete abortion (spontaneous
      miscarriage and illegally induced) in South Africa. DESIGN: Multicentre,
      prospective, descriptive study. SETTING: Fifty-six public hospitals in nine
      provinces (a stratified, random sample of all hospitals treating gynaecological
      emergencies). PATIENTS: All women of gestation under 22 weeks who presented with
      incomplete abortion during the 2-week study period. MAIN OUTCOME MEASURES:
      Incidence of, morbidity associated with and mortality from incomplete abortion.
      MAIN RESULTS: An estimated 44686 (95% CI 35633-53709) women per year were
      admitted to South Africa's public hospitals with incomplete abortion. An
      estimated 425 (95% CI 78-735) women die in public hospitals from complications of
      abortion. Fifteen per cent (95% CI 13-18) of patients have severe morbidity while
      a further 19% (95% CI 16-22) have moderate morbidity, as assessed by categories
      designed for the study which largely reflect infection. There were marked inter
      provincial differences and inter-age group differences in trimester of
      presentation and proportion of patients with appreciable morbidity. CONCLUSIONS:
      Incomplete abortions and, in particular, unsafe abortions are an important cause
      of mortality and morbidity in South Africa. The methods used in this study
      underestimate the true incidence for reasons that are discussed. A high priority
      should be given to the prevention of unsafe abortion.

PMID- 9254786
TI  - Management of incomplete abortions at South African public hospitals. National
      Incomplete Abortion Study Reference Group.
AB  - OBJECTIVE: The objective of this report was to review and describe the management
      of incomplete abortion by public sector hospitals. DESIGN: A descriptive study in
      which data were collected prospectively from routine hospital records on all
      women admitted with incomplete abortion to a stratified random sample of
      hospitals between 14 and 28 September 1994. SETTING: Public sector hospitals in
      South Africa. PATIENTS: Women with incomplete abortions. MAIN OUTCOME MEASURES:
      Length of hospital stay, details of medical management, details of surgical
      management, determinants of the above. MAIN RESULTS: Data were collected on 803
      patients from the 56 participating hospitals. Of these, 767 (95.9%) were in
      hospital for 1 day or more, and 753 (95.3%) women underwent evacuation of the
      uterus. Sharp curettage was the method employed in 726 (96.9%) and general
      anaesthesia was used for 601 (68%) of the women requiring uterine evacuation.
      Antibiotics were prescribed for 396 (49.5%) and blood transfusions were
      administered to 125 (17%) women. Statistical analysis showed length of stay to be
      longer in small hospitals (under 500 beds) and when the medical condition was
      more severe. Antibiotic usage and blood transfusion were more common with
      increasing severity and a low haemoglobin level on admission. However, some
      inappropriate management was identified with regard to both. MAIN CONCLUSIONS: It
      is suggested that uncomplicated incomplete abortion can be more effectively and
      safely managed using the manual vacuum aspiration technique with
      sedation/analgesia as an outpatient procedure. Attention should be directed at
      the introduction of this management routine at all types of hospital and to the
      ensuring of appropriate management of women with complicated abortion.

PMID- 9254787
TI  - An analysis of the cost of incomplete abortion to the public health sector in
      South Africa--1994.
AB  - OBJECTIVE: To analyse the medical costs incurred in treating women for incomplete
      abortion. This study was performed in conjunction with a nationwide survey of
      women who presented to public hospitals with incomplete abortion in 1994. DESIGN:
      Cost analysis with two modified Delphi panels used to develop models of resource
      use reflecting three severity categories of symptoms and three hospital treatment
      settings. SETTING: Public hospitals in South Africa. PARTICIPANTS: A panel of 15
      senior level obstetrician/ gynaecologists and a second panel of 11 patient care
      managers representing district, regional and tertiary level hospitals in 7
      provinces. MAIN RESULTS: A conservative estimate of the total cost of treating
      women is R18.7 million +/- R3.5 million for 1994. An estimated R9.74 million +/-
      R1.3 million of this was spent treating women with 'unsafe' incomplete abortions.
      CONCLUSIONS: The management of incomplete abortion requires significant public
      sector expenditure. The long-term indirect costs to women, their families and
      communities are discussed and treatment costs estimated so that unmet needs for
      medical care resulting from unsafe abortions can be addressed.

PMID- 9254788
TI  - The increasing burden of tuberculosis in rural South Africa--impact of the HIV
      epidemic.
AB  - OBJECTIVE: To determine the impact of the HIV epidemic on tuberculosis caseload
      in rural South Africa. SETTING: Hlabisa health district, KwaZulu-Natal. METHODS:
      Demographic and clinical data were extracted from the tuberculosis database for
      the period, May 1991-June 1995. The attributable fraction of HIV-infected
      tuberculosis cases was estimated from the prevalence of HIV infection in
      tuberculosis cases and the prevalence of HIV infection in women attending
      antenatal clinics. RESULTS: Between 1991 and 1995, the annual tuberculosis
      caseload increased from 301 to 839 cases. Tuberculosis accounted for 4.7% of all
      admissions in 1989 and 8.3% in 1995 (P < 0.0001). The incidence of tuberculosis
      increased from 154/100,000 in 1991, to 413/100,000 in 1995. The proportion with
      smear-positive pulmonary disease fell from 65% to 56% (P = 0.04), and pleural
      tuberculosis accounted for 7.5% of disease in 1991 and 18% in 1995 (P = 0.002).
      The minimum HIV prevalence in patients with tuberculosis increased from 8.7% in
      1991 to 28.3% in 1995, and the proportion of tuberculosis cases attributable to
      HIV infection was estimated to be at least 44% in 1995. CONCLUSION: The burden of
      HIV-related tuberculosis is increasing rapidly in rural South Africa and is
      exerting a negative impact. Innovative approaches to control will be needed to
      cope with it effectively.

PMID- 9254789
TI  - Costs and cost-effectiveness of alternative tuberculosis management strategies in
      South Africa--implications for policy.
AB  - OBJECTIVE: To conduct an economic analysis of the Hlabisa community-based
      directly observed therapy management strategy for tuberculosis and to project
      costs of three alternative strategies. SETTING: Hlabisa health district, KwaZulu
      Natal, South Africa. METHODS: An economic analysis comparing the current
      tuberculosis management strategy in Hlabisa with three alternative strategies
      (the Hlabisa strategy prior to 1991 based on hospitalisation, the national
      strategy and sanatorium care) in terms of costs to both health service and
      patient and of cost-effectiveness. RESULTS: The current Hlabisa strategy was the
      most cost-effective (R3799 per patient cured), compared with R98307 for the
      strategy used prior to 1991, R9940 for the national strategy, and R11145 for
      sanatorium care. Between 71% and 88% of treatment costs lie with the health
      service, and hospitalisation (R119 per day) is the most expensive item. Prolonged
      hospitalisation is extremely expensive, but community care is cheaper (community
      clinic visit, R28; community health worker visit, R7). The total cost of
      supervising a patient in the community under the current Hlabisa strategy was
      R503, equivalent to 4.2 days in hospital. Drug costs (R157) are equivalent to
      just 1.3 days in hospital. CONCLUSION: Cost to both health service and patient
      can be substantially reduced by using community-based directly observed therapy
      for tuberculosis, a strategy that is cheap and cost-effective in Hlabisa. These
      findings have important national implications, supporting the goals of the new
      tuberculosis control programme.

PMID- 9254790
TI  - Maternal and child health indicators in a rural South African health district.
AB  - OBJECTIVE: To measure important maternal and child health indicators in a rural
      health district as part of the process of developing a comprehensive district
      health information system. DESIGN: A modified Expanded Programme on Immunisation
      cluster sample survey. SETTING: Hlabisa health district, KwaZulu-Natal.
      PARTICIPANTS: 480 mothers (or carers) of children aged 12-35 months surveyed in
      32 clusters. INTERVENTIONS: A questionnaire was administered and Road-to-Health
      cards were examined. MAIN OUTCOME MEASURES: Proportion of women receiving
      antenatal care and delivering in a health facility; knowledge and understanding
      of vaccination; and recall of vaccination history. Proportion of children with a
      Road-to-Health card, overall coverage of each vaccine, coverage at 12 months of
      age and proportion receiving an immunogenic dose. RESULTS: Most mothers (91%) had
      attended antenatal care, 77% had received tetanus toxoid and 83% delivered in a
      health facility. Only 14 children (3%) had never received a Road-to-Health card
      and 73% had one available at the time of the survey. Overall immunisation
      coverage was high (80-98%), as was the proportion receiving an immunogenic dose
      of each vaccine (78-98%). However, only 76% had received all the vaccines due to
      a 12-month-old child, and only 88% of these had received all doses by 12 months
      of age. CONCLUSIONS: While the key maternal health indicators measured here are
      reassuring, there is still room for improvement in the child health indicators.
      The proportion of women receiving antenatal care and delivering in a health
      facility is very high, but the proportion of children receiving all vaccines can
      be improved upon, as can the timing of immunisation. The results of this survey
      are being used to strengthen further the primary health care services in the
      district.

PMID- 9254791
TI  - Smoking in urban pregnant women in South Africa.
AB  - AIM: To estimate the exposure to active and passive smoking of pregnant women in
      South Africa and to determine their knowledge and behaviour with regard to
      smoking during pregnancy. METHODS: A questionnaire was completed by pregnant
      women attending antenatal services in four South African cities. Questions were
      asked about smoking status, beliefs on the health effects of tobacco smoke during
      pregnancy, exposure to passive smoking and behavioural changes with regard to
      smoking during pregnancy. Women from different ethnic groups and social classes
      participated. RESULTS: The study population was 394 pregnant women. Of these 42%
      were black, 29% coloured and 10% Indian women, who used public antenatal
      services, and 19% were pregnant women (ethnicity unspecified) who attended
      private obstetric practices. Of the coloured women, 47% smoked; for the black and
      Indian women and those who attended a private practice, the smoking rates were
      4%, 3% and 28%, respectively. Approximately 90% of the pregnant women knew it was
      unhealthy to smoke during pregnancy. Most women who smoked stopped or reduced
      tobacco use during their pregnancy. Of the pregnant women, 70% lived with at
      least one smoker in the house. CONCLUSIONS: Few black and Indian pregnant women
      in South Africa smoke, while coloured pregnant women smoke heavily. Quitting
      programmes should be targeted at them when they attend antenatal services.
      Pregnant women and their families should be alerted to the impact of
      environmental tobacco smoke, since so many are passive smokers during pregnancy.

PMID- 9254792
TI  - Cost-effective on-site screening for anaemia in pregnancy in primary care
      clinics.
AB  - OBJECTIVE: To determine the feasibility, accuracy and cost of developing a system
      of on-site screening for anaemia in pregnancy in primary care clinics. SETTING:
      Mobile clinic team in Hlabisa health district, KwaZulu-Natal. METHODS: Four
      hundred and forty-nine consecutive women attending antenatal clinics were
      screened for anaemia (haemoglobin < 10 g/dl) using copper sulphate solution; the
      results were compared with true haemoglobin levels as determined by an automated
      analyser. Three hundred women had haemoglobin concentration estimated with a
      portable haemoglobinometer and results compared with those from the automated
      analyser. RESULTS: Screening with copper sulphate solution was highly sensitive
      (95.7%) but had low positive predictive value for anaemia (37.2%). Haemoglobin
      concentration estimated by haemoglobinometer correlated highly with results from
      the analyser (r = 0.82; P < 0.0001), and the mean difference in concentrations
      between the two methods was 1.1 g/dl. The average cost of screening all women
      with copper sulphate solution (6 cents/sample) and determining the true
      concentration in those screened as possibly anaemia (R2.64/sample) was 72 cents
      per woman. The cost of using an automated analyser was R6.20 per sample.
      CONCLUSION: Combined use of copper sulphate solution and a haemoglobinometer is a
      feasible, accurate and cost-effective way of screening for and diagnosing anaemia
      in pregnant women, on-site, in primary care clinics.

PMID- 9254793
TI  - Virodene--support misguided.

PMID- 9254795
TI  - Virodene--support misguided.

PMID- 9254796
TI  - Occupational lung diseases in ex-mineworkers--misinformed critique.

PMID- 9254797
TI  - Ophthalmia neonatorum prophylaxis--can we do it more cost-effectively?

PMID- 9254798
TI  - Curriculum development for the rural specialist.

PMID- 9254799
TI  - Curriculum development for the rural specialist.

PMID- 9254801
TI  - Trace elements and osteoporosis.

PMID- 9254802
TI  - The concept of rational drug use.

PMID- 9254803
TI  - Eclampsia--cause and prevention.

PMID- 9254804
TI  - Interferon found helpful in herpes genitalis case.

PMID- 9254805
TI  - An audit of asthma care at Khayelitsha Community Health Centre.

PMID- 9254806
TI  - Malnutrition--food parcels and follow-up.

PMID- 9254807
TI  - Hospital kickbacks.

PMID- 9254808
TI  - Developing health in the Cape.

PMID- 9254809
TI  - To clone or not to clone?

PMID- 9254810
TI  - MASA supports doctors' role in community.

PMID- 9254811
TI  - Obesity--anything new?

PMID- 9254812
TI  - Stroke incidence in South Africa.

PMID- 9254814
TI  - Health sector co-operation in southern Africa--priorities for action.

PMID- 9254813
TI  - Malaria in the new South Africa--are district health systems and current malaria
      control strategies compatible?

PMID- 9254815
TI  - Where do we go from here--the future of nephrology in South Africa.

PMID- 9254817
TI  - Paediatric burns in a rural South African district hospital.
AB  - OBJECTIVES: To describe the epidemiology, clinical features, management and
      outcome of children with burns admitted to a rural district hospital. DESIGN: A
      retrospective analysis of the case notes of consecutive cases of paediatric
      burns. SETTING: Hlabisa Hospital, KwaZulu-Natal-a 450-bed rural district hospital
      serving approximately 200,000 people. SUBJECTS: All cases of paediatric burns
      (age < 12 years) admitted to Hlabisa Hospital in 1994. MAIN OUTCOME MEASURES:
      Number of admissions, month of admission, age, sex, time to presentation, site of
      burn, complications, number of surgical procedures, adherence to management
      protocol and outcome. RESULTS: One hundred and forty-nine children presented to
      the outpatient department in 1994 and 88 (59%) were admitted. The median age of
      those admitted was 36 months with 66 (75%) aged less than 5 years; 42 (48%) were
      boys. Thirty-nine children (44%) were admitted during the four winter months of
      May to August. The average interval from the time of the burn to presentation at
      hospital was 42 hours (range 1-120). Sixty-eight burns (77%) were due to hot
      fluid or food burning the legs, trunk or arms. There was a high level of
      morbidity. Nineteen (22%) children developed wound infections, 5 (6%) developed
      contractures and 20 (23%) required a total of 32 surgical procedures. There was 1
      death. Burns were responsible for more paediatric patient days spent in hospital
      than any condition other than malnutrition, and a longer length of stay was
      associated with delay in presentation. Children presenting within 24 hours of the
      burn had a mean length of stay of 12.8 days, compared with 25.2 days (P = 0.03)
      for children presenting 24 hours or more after the burn. Twenty of the 22
      children who stayed for longer than 3 weeks or who required transfer were judged
      to have been managed inadequately in at least one respect compared with 3 of 48
      who were discharged within 2 weeks or not transferred (P < 0.001). CONCLUSION:
      This study shows that paediatric burns are an important cause of morbidity and
      contribute significantly to inpatient stay in this rural setting. The lengthy
      delay from time of burn to presentation at hospital is of serious concern and our
      results show that this delay is associated with increased hospital stay. As most
      burns were due to spillage of hot fluids or food there seems to be significant
      potential for preventive interventions. Community-based studies would help to
      estimate the true incidence of burns and would contribute to an understanding of
      the reasons for delay in presentation. The information gathered is being used to
      inform the development of a burns prevention programme.

PMID- 9254816
TI  - The cost and benefit of prophylaxis against deep vein thrombosis in elective hip
      replacement. DVT/PE Prophylaxis Consensus Forum.
AB  - A consensus forum was convened to evaluate the economic considerations associated
      with prophylaxis against thrombo-embolic disease in patients undergoing hip
      replacement therapy in South Africa. This forum consists of orthopaedic surgeons,
      vascular surgeons and a statistician. METHODS: The forum was instructed to
      evaluate the economic costs of the commonly used forms of prophylaxis of thrombo
      embolism in patients undergoing hip replacement surgery in South Africa, looking
      at short-term events only. The methods used for the prophylaxis of thrombo
      embolism in South Africa were determined by a postal survey. A decision tree was
      constructed to determine the events that will occur after a clinical decision to
      use no prophylaxis. The probabilities of these events were then determined.
      Protocols for and costs of prophylaxis and treatment were established. With the
      decision tree and these costs, the cost of the various modalities of prophylaxis
      was then determined. RESULTS: The probability, determined by the forum, of
      developing a deep-vein thrombosis (DVT) when no prophylaxis is used was 0.5, with
      a mortality rate of 2.1%. The cost of this decision was R875. No prophylaxis
      given, but a venogram performed on day 7, reduced the mortality rate to 0.7%;
      however, this cost R3 017. The cost of low-molecular-weight heparin was R1 223
      (probability 0.26, mortality rate 1.1%), while unfractionated heparin with a
      graduated compression stocking (GCS) cost R1 351 (probability 0.24, mortality
      rate 1%). Aspirin with a GCS cost R777 (probability 0.35, mortality rate 1.5%).

PMID- 9254818
TI  - Hepatitis C virus infection rate in volunteer blood donors from the Western Cape-
      comparison of screening tests and PCR.
AB  - INTRODUCTION: Hepatitis C virus (HCV) antibody seroprevalence studies
      overestimate the true infection rate. No data exist on the incidence of HCV or
      its clinical features in blood donors of sub-Saharan Africa. AIMS: To establish
      the true incidence of HCV infection in volunteer blood donors in the Western
      Cape, and compare risk factors and clinical and biochemical features of viraemic
      and non-viraemic subjects. METHODS: All donors attending the Western Province
      Blood Transfusion Service between December 1992 and August 1994 were screened
      prospectively for anti-HCV using the Abbott second-generation assay. Positive
      donors were evaluated clinically and biochemically. Their sera were examined for
      HCV-RNA by the polymerase chain reaction (PCR). RESULTS: Of 66314 donors
      screened, 275 (0.41%) were anti-HCV-positive. Of these 13.6% were PCR-positive
      (0.056% of all donors). PCR-positive patients had more risk factors for HCV
      acquisition (P < 0.01), symptoms of hepatitis (P = 0.02) and clinical signs of
      liver disease (P = 0.05) and higher alanine (P < 0.0001) and aspartate
      aminotransferase levels (P < 0.0001) than PCR-negative donors. However, clinical
      and biochemical features did not discriminate adequately between PCR-positive and
      negative donors. Liver biopsies performed in 9 of 13 PCR-positive cases showed
      mild inflammation, but no cirrhosis.

PMID- 9254819
TI  - Stroke incidence rates among black residents of Harare--a prospective community
      based study.
AB  - OBJECTIVE: To estimate the crude incidence rates of cerebrovascular accidents
      among the black residents of Harare. DESIGN: Prospective community-based study.
      SETTING: Black residents of Harare, Zimbabwe. PARTICIPANTS: Two hundred and
      seventy-three 'first-ever' strokes prospectively identified over a 12-month
      period. MAIN OUTCOME STUDY FACTORS: Cerebrovascular accident first-week fatality
      rate; age- and sex-related incidence. RESULTS: The crude incidence rate was
      estimated to be 30.7 per 100000 (95% confidence interval 27.1-34.4) and the
      standardised rate was 68 per 100000. Fifty-one per cent of stroke victims were
      below the age of 54 years. Thirty-five per cent of patients died within 1 week of
      the stroke. Overall, the age-specific rates for both sexes rose with age, with
      the rates for women being higher at all age strata except for the group 45-54
      years. CONCLUSION: With a standardised rate of 68 per 100000 and a first-week
      mortality rate of 35%, stroke must now be considered an important cause of
      morbidity and mortality in the population.

PMID- 9254820
TI  - Diagnostic disagreement--the lessons learnt from malaria diagnosis in Mpumalanga.
AB  - Diagnostic tests that require human interpretation will always be susceptible to
      error. This may lead to delays in initiating effective therapy for potentially
      fatal conditions. The Malaria Control Programme in South Africa has historically
      relied on the microscopic examination of Giemsa-stained thick blood smears to
      confirm the clinical diagnosis of malaria. The level of agreement of malaria
      laboratory diagnosis performed by the four laboratories serving the Mpumalanga
      Province Malaria Control Programme was investigated. The disagreement between the
      laboratories argues in favour of a uniform training and quality assurance
      programme or the introduction of alternative diagnostic modalities. It should
      also serve as a caution against diagnostic complacency in other public health
      programmes.

PMID- 9254821
TI  - Georgius Agricola: 1494-1555--mining engineer and physician. His contribution to
      occupational medicine and the aetiology of bronchus carcinoma.

PMID- 9254822
TI  - Virodene--support misguided.

PMID- 9254823
TI  - Virodene--support misguided.

PMID- 9254824
TI  - Virodene--support misguided.

PMID- 9254825
TI  - The 'impending' AIDS catastrophe!

PMID- 9254826
TI  - Cytological screening for cervical cancer--what are its opportunity costs?

PMID- 9254827
TI  - Cytological screening for cervical cancer--what are its opportunity costs?

PMID- 9254829
TI  - Cytological screening for cervical cancer--what are its opportunity costs?

PMID- 9254828
TI  - Cytological screening for cervical cancer--what are its opportunity costs?

PMID- 9254830
TI  - Feasibility of universal screening for cervical cancer in rural South Africa.

PMID- 9254831
TI  - Screening for cancer of the cervix in South Africa.

PMID- 9254834
TI  - Establishment of human DNA and plasma or serum banks for research purposes--a
      proposal.

PMID- 9254835
TI  - The quality and relationship of referral and reply letters.

PMID- 9254837
TI  - National Association of Pharmaceutical Wholesalers--request to reduce gross
      margins on prescription medicines.

PMID- 9254839
TI  - Antigenic and genetic characterization of Legionella proteins: contributions to
      taxonomy, diagnosis and pathogenesis.

PMID- 9254838
TI  - ABH and related histo-blood group antigens in normal & malignant human
      endometrium in relation to genetic and hormonal factors.
AB  - Recent immunohistochemical studies have shown that endometrial carcinomas are
      characterized by changes in glycosylation involving histo-blood group antigens.
      These carbohydrate determinants are present not only on erythrocytes but are also
      expressed by epithelial cells. Their expression herein has been shown to be
      related to the genetic status of the individual in terms of the ABO, Lewis and
      ABH-secretor type. Moreover, they show changes in expression relating to
      development, tissue-type, differentiation, cell-motility and malignancy.
      Meanwhile, most studies performed on endometrial tissue have not considered duly
      that histo-blood group antigen expression herein may be influenced by genetic and
      hormonal factors. Using immunohistochemistry and MABs with specificity to ABH-
      and related histo-blood group antigens with different peripheral core structures
      we have studied the expression of these carbohydrates in the human endometrium in
      relation to genetic and hormonal factors. The present paper presents a summary
      and a discussion of present knowledge on expression of histo-blood group antigens
      in the normal and malignant human endometrium. In addition, the possible
      regulatory mechanisms that control their expression in the endometrium are
      discussed. The histo-blood group phenotype of normal endometrial epithelial cells
      show great complexity. Variations in expression are related to the genetic
      status, i.e., the ABO, Lewis and ABH-secretor status. However, our findings
      suggest that the regulation of Lewis antigen expression in the endometrium
      differs from that in erythrocytes. Moreover, expression of histo-blood group and
      related carbohydrates varies with layer, mucosal histology, cell-type and hormone
      levels in serum. In glands in the functionalis and basalis, the histo-blood group
      phenotype is characterized by a predominant expression of sialylated types 2 and
      3 chains. Expression of ABH determinants is, in general, low. However, the
      expression of fucosylated and terminal ABH determinants vary with the menstrual
      cycle, degree of proliferation and hormone levels in serum. The secretory
      phenotype is characterized by an increased expression of type-1 chain antigens,
      and by expression of sialylated chains as S-Tn, MS-Le(a), DS-Lac. A/B transferase
      protein expression was found to correlate with E2 levels in serum. These findings
      in conjunction with studies of glycosyltransferase activity in murine endometrial
      cell strongly suggest that the endometrial epithelial cell histo-blood group
      phenotype is also modulated by the ovarian hormones. The histo-blood group
      phenotype of endometrial carcinomas and precursor lesions is also influenced by
      the ABO, Lewis and secretor-status. Except for loss of A/B transferases and A/B
      antigens, which appear to be a late event, the changes are demonstrable also in
      preneoplastic endometrial cells. The malignant phenotype is characterized by an
      increased expression of type-1 chain carbohydrates. ABH-secretors express H and
      Le(b) antigens in addition to Le(a) and S-Le(a) antigens, whereas ABH-non
      secretors express Le(a), and S-Le(a) determinants mainly. Moreover, endometrial
      carcinomas express Tn antigen, and sialylated carbohydrates, which are expressed
      in luteal phases of the normal endometrium, i.e., S-Tn, DS-Lac, and MS-Le(a)
      antigens. Thus the histo-blood group phenotype of endometrial carcinoma cells in
      many ways shows a resemblance to that of secretory endometria. The relation
      between expression of T, S-T and A/B transferase protein and E2 levels in serum
      was maintained in endometrial carcinomas. Expression of H, Le(b), LeX, S-LeX, and
      LeY was related to the tumour grade, whereas only expression of H determinants
      was related to the FIGO stage. In accord, recent studies have suggested that
      expression of H and Le(b) antigens in endometrial carcinomas may be correlated
      with prognosis. An increased activity of alpha 1-2 and alpha 1-3/4
      fucosyltransferases has recently been demonstrated in endometrial carci

PMID- 9254840
TI  - Towards a unified nomenclature describing voltage-gated calcium channel genes.
AB  - A unified nomenclature for describing voltage-gated calcium channel genes is
      proposed. The terminology has been approved by the HUGO/GDB nomenclature
      committee.

PMID- 9254841
TI  - Assignment of human genes for beta 2 and beta 4 subunits of voltage-dependent
      Ca2+ channels to chromosomes 10p12 and 2q22-q23.
AB  - We have used human beta 2 and beta 4 cDNA probes to map the genes encoding two
      isoforms of the regulatory beta subunit of voltage-activated Ca2+ channels, viz.
      CACNB2 (beta 2) and CACNB4 (beta 4), to human chromosomes 10p12 and 2q22-q23,
      respectively, by fluorescence in situ hybridization. The gene encoding the beta 2
      protein, first described as a Lambert-Eaton myasthenic syndrome (LEMS) antigen in
      humans, is found close to a region that undergoes chromosome rearrangements in
      small cell lung cancer, which occurs in association with LEMS. CACNB2 (beta 2)
      and CACNB4 (beta 4) genes are members of the ion-channel gene superfamily and it
      should now be possible to examine their loci by linkage analysis of ion-channel
      related disorders. To date, no such disease-related gene has been assigned to
      10p12 and 2q22-q23.

PMID- 9254842
TI  - Studies of the CAG repeat in the Machado-Joseph disease gene in Taiwan.
AB  - Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar
      degeneration characterized by cerebellar ataxia and pyramidal signs associated in
      varying degrees with a dystonic-rigid extrapyramidal syndrome or peripheral
      amyotrophy. Unstable CAG trinucleotide repeat expansion in the MJD gene on the
      long arm of chromosome 14 has been identified as the pathological mutation for
      MJD. While investigating the distribution of CAG repeat lengths of the MJD gene
      in Taiwan's population, we have identified 18 MJD-affected patients and 12 at
      risk individuals in seven families. In addition, we have analyzed the range of
      CAG repeat lengths in 96 control individuals. The CAG repeat number ranged from
      13 to 44 in the controls and 72-85 in the affected and at-risk individuals. Our
      results indicated that the CAG repeat number was inversely correlated with the
      age of onset. The differences in CAG repeat length between parent and child and
      between siblings are greater with paternal transmission than maternal
      transmission. Our data show a tendency towards the phenomenon of anticipation in
      the MJD families but do not support unidirectional expansion of CAG repeats
      during transmission. We also demonstrated that PCR amplification of the CAG
      repeats in the MJD gene from villous DNA was possible and might prove useful as a
      diagnostic tool for affected families in the future.

PMID- 9254843
TI  - Mistyping frequency of the angiotensin-converting enzyme gene polymorphism and an
      improved method for its avoidance.
AB  - A DD genotype of the angiotensin I-converting enzyme gene has been implicated in
      various diseases. However, genotype frequencies differ between previous reports,
      and data on the association of DD genotype with disease are sometimes
      conflicting. Although elimination of mistyping is of crucial importance,
      assessment of the accuracy of currently adopted typing methods has rarely been
      performed. Mistyping of the DD genotype is reported to occur by a conventional
      method with insertion/ deletion (I/D) flanking primers using polymerase chain
      reaction (PCR). We investigated whether currently adopted genotyping methods by
      PCR are reliable or not. We genotyped 248 patients by conventional PCR methods
      with I/D flanking primers with or without dimethyl sulfoxide (DMSO), and
      confirmed the DD genotype with insertion-specific primers with or without DMSO.
      Mistyping occurred frequently, not only in both methods without DMSO but also in
      a modified method with I/D flanking primers with inclusion of DMSO. Typing by
      these methods proved to lead to erroneous results more frequently than had been
      previously thought. To reduce mistyping frequency, initial PCR genotyping with
      I/D flanking primers with an inclusion of DMSO, followed by confirmation of the
      DD genotype by insertion-specific primers with DMSO, is recommended.

PMID- 9254844
TI  - A family exhibiting heteroplasmy in the human mitochondrial DNA control region
      reveals both somatic mosaicism and pronounced segregation of mitotypes.
AB  - A family exhibiting heteroplasmy at position 16355 in hypervariable region I of
      the human mtDNA control region has been identified. This family consists of a
      mother, daughter, and son. DNA samples extracted from blood stains, buccal swabs,
      and hairs from these individuals were amplified by PCR and sequenced utilizing
      fluoresence-labeled dye terminator chemistry in an automated DNA sequencer. In
      both the daughter and mother, heteroplasmy was observed in DNA extracted from
      blood stains, buccal swabs, and hairs. In the blood stains, the proportion of
      cytosine was greater than thymine in both individuals. Buccal swab extracts
      showed a more balanced contribution from the two nucleotides. Telogenic hair root
      and hair shaft samples exhibited a wide range of nucleotide contributions at this
      position, from predominately cytosine in some samples to predominately thymine in
      others. The apparent stochastic segregation of mitotypes in hair samples is
      discussed from a forensic viewpoint, and the mechanism of mtDNA heteroplasmy is
      considered.

PMID- 9254845
TI  - Cytogenetic rearrangements involving the loss of the Sonic Hedgehog gene at 7q36
      cause holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a genetically heterogeneous disorder that affects the
      midline development of the forebrain and midface in humans. As a step toward
      identifying one of the HPE genes, we have set out to refine the HPE3 critical
      region on human chromosome 7q36 by analyzing 34 cell lines from families with
      cytogenetic abnormalities involving 7q, 24 of which are associated with HPE.
      Genomic clones surrounding the DNA marker D7S104, which has previously been shown
      to be in the HPE3 critical region, have been examined by fluorescent in situ
      hybridization and microsatellite analysis of our panel of patient cell lines. We
      report the analysis of a cluster of four translocation breakpoints within a 300
      kb region of 7q36 that serves to define the minimal critical region for HPE3 and
      that has directed the search for candidate genes. The human Sonic Hedgehog (hSHH)
      gene maps to this region and has been shown to be HPE3 on the basis of mutations
      within the coding region of the gene. We present evidence that cytogenetic
      deletions and/or rearrangements of this region of chromosome 7q containing Sonic
      Hedgehog, and translocations that may suppress Sonic Hedgehog gene expression
      through a position effect are common mechanisms leading to HPE.

PMID- 9254846
TI  - How common are common fragile sites: variation of aphidicolin-induced chromosomal
      fragile sites in a population of the deer mouse (Peromyscus maniculatus).
AB  - Aphidicolin (APC)-induced chromosomal gaps and breaks were analyzed for ten deer
      mice (Peromyscus maniculatus) from a natural population. The FSM statistical
      methodology was used to identify fragile sites as chromosomal loci exhibiting
      significantly non-random numbers of gaps/breaks in each individual and enabled an
      assessment of variation in fragile sites among the individuals. The individual
      deer mice exhibited as few as 7 to as many as 19 of the populational total of 34
      sites. Two sites were fragile in all individuals and 13 sites were fragile in
      single individuals only. Defined by populational frequencies of greater than 50%,
      high-frequency fragile sites constituted 26% of the populational total.
      Approximately 35% of the total fragile sites were fragile in 20-40% of the
      population (low-frequency fragile sites) and about 38% were fragile in single
      individuals only. Analysis of the data pooled over all individuals identified
      significantly non-random breakage at 80 sites, 47 of which were not identified as
      fragile in any single individual. It appears, therefore, that fragile site
      identifications from pooled data have fostered an inflated estimate of the
      numbers and frequencies of common fragile sites. Comparison of the fragile site
      and spontaneous breakage (control) data suggest that APC-induced fragile sites
      represent regions of chromosomes that experience elevated levels of somatic
      mutation. Additionally, the occurrence of APC-induced fragile sites at or near
      the interstitial breakpoints of two pericentric-inversion polymorphisms in this
      population supports the hypothesis that fragile sites experience an increased
      rate of meiotic chromosomal mutation and are predisposed to undergo phylogenetic
      rearrangement.

PMID- 9254847
TI  - Phenylketonuria and the peoples of Northern Ireland.
AB  - The comparison of regional patterns of recessive disease mutations is a new
      source of information for studies of population genetics. The analysis of
      phenylketonuria (PKU) mutations in Northern Ireland shows that most major
      episodes of immigration have left a record in the modern genepool. The mutation
      165T can be traced to the Palaeolithic people of western Europe who, in the
      Mesolithic period, first colonised Ireland. R408W (on haplotype 1) in contrast,
      the most common Irish PKU mutation, may have been prevalent in the Neolithic
      farmers who settled in Ireland after 4500 BC. No mutation was identified that
      could represent European Celtic populations, supporting the view that the
      adoption of Celtic culture and language in Ireland did not involve major
      migration from the continent. Several less common mutations can be traced to the
      Norwegian Atlantic coast and were probably introduced into Ireland by Vikings.
      This indicates that PKU has not been brought to Norway from the British Isles, as
      was previously argued. The rarity in Northern Ireland of IVS12nt1, the most
      common mutation in Denmark and England, indicates that the English
      colonialization of Ireland did not alter the local genepool in a direction that
      could be described as Anglo-Saxon. Our results show that the culture and language
      of a population can be independent of its genetic heritage, and give some insight
      into the history of the peoples of Northern Ireland.

PMID- 9254848
TI  - A novel de novo mutation in exon 14 of the fibrillin-1 gene associated with
      delayed secretion of fibrillin in a patient with a mild Marfan phenotype.
AB  - The Marfan syndrome, an autosomal dominant heritable disorder of connective
      tissue, is caused by mutations in the gene for fibrillin-1, FBN1. A novel FBN1
      mutation was identified using temperature-gradient gel electrophoresis of a
      reverse-transcribed polymerase chain reaction product spanning exons 14 to 16.
      The mutation, G1760A, is predicted to result in the amino acid substitution C587Y
      and thus to disrupt one of the disulfide bonds of the calcium-binding epidermal
      growth factor-like module encoded by exon 14. C587Y was found to be a de novo
      mutation in a relatively mildly affected 15-year-old girl whose clinical
      phenotype was characterized mainly by ectopia lentis and thoracic scoliosis.
      Metabolic labeling of cultured dermal fibroblasts from the affected patient
      demonstrated delayed secretion of fibrillin with normal synthesis and no decrease
      in incorporation into the extracellular matrix compartment. Fibrillin
      immunostaining of confluent dermal fibroblast cultures revealed no visible
      difference between the patient's cells and control cells. Characterization of
      many different FBN1 mutations from different regions of the gene may provide a
      better understanding of clinical and biochemical genotype-phenotype
      relationships.

PMID- 9254849
TI  - A missense mutation in the FALDH gene identified in Sjogren-Larsson syndrome
      patients originating from the northern part of Sweden.
AB  - Sjogren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized
      by congenital ichthyosis, spastic di- or tetraplegia, and mental retardation. SLS
      has been reported to occur in many populations but the highest incidence is in
      the north of Sweden. The gene causing SLS encodes a fatty aldehyde dehydrogenase
      (FALDH). In the present study, a point mutation in exon 7 of the FALDH gene was
      found in SLS patients of northern Swedish origin. The mutation consists of a C-to
      T exchange at nucleotide position 943 in the cDNA. As a consequence, a highly
      conserved proline is replaced by a serine. The mutation was found in 49 out of 58
      affected chromosomes and could be the most widely spread SLS mutation in the
      world.

PMID- 9254850
TI  - Inheritance of cleft palate in Italy. Evidence for a major autosomal recessive
      locus.
AB  - Although several studies have demonstrated familial aggregation of nonsyndromic
      cleft palate (CP), the mode of inheritance still remains uncertain. We report the
      results of complex segregation analysis performed in families of 357 consecutive
      newborns affected with nonsyndromic CP (i.e., CP not a component feature of
      malformation syndrome, sequence or association), and registered in the North East
      Italy and Emilia Romagna congenital malformation registries in the period 1981
      1993. This sample, based on a large number of consecutive births, in a well
      defined geographical area, with quality control to detect associated anomalies
      and malformation syndromes, is independent of the number of affected subjects in
      the family and of CP severity, fitness, and survival. We have analyzed, using the
      mixed model, the whole sample of nonsyndromic CP, including isolated (i.e.,
      without other anomalies) CP (CPI) and CP associated with at least one other
      anomaly (CPA), for which a diagnosis of malformation syndrome was not possible.
      When nonsyndromic CP (including CPA) are considered in the analysis, there is no
      heterogeneity between CPA and CPI nor between CP including hard palate (CPH) and
      CP of the soft palate only (CPS). POINTER and COMDS programs cannot discriminate
      between alternative genetic models; only the hypothesis of non-genetic
      transmission is rejected. The COMDS analysis two-locus model, which indicates
      that a modifier locus (or loci) operates in addition to a single major locus
      (SML), does not show evidence of better fit than SML, polygenic, and
      multifactorial models. When the severity parameter (defined as CPH and CPS) is
      added, CPI and CPA show heterogeneity. Eventually, when the analysis is limited
      to CPI and includes information on severity, a recessive SML, with low penetrance
      and determining CPH, provides a significant best fit. To have defined a genetic
      model for CPI and provided evidence for SML inheritance suggests that genetic
      linkage studies could be implemented. This conclusion is in agreement with
      previous studies which showed a significant association between alleles of
      transforming growth factor alpha and CP only in humans, and that single recessive
      genes may play a crucial role during palatogenesis in mice as well as in Brittany
      spaniels. Application of the candidate genes to human CPH families could reveal
      whether these genes are involved.

PMID- 9254851
TI  - Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the
      risk of coronary artery disease in Chinese.
AB  - The homozygous deletion allele (DD) of the angiotensin-I converting enzyme (ACE)
      gene and the T235 homozygote of the angiotensinogen (AGT) gene have been reported
      to be correlated with an increased prevalence of coronary artery disease (CAD)
      and myocardial infarction (MI). The importance of the DD genotype and T235
      homozygote as genetic risk factors for CAD in Chinese remains uncertain. This
      study included 426 patients who underwent coronary angiography and 180 healthy
      subjects without clinical evidence of CAD. Coronary angiography identified 268
      patients with CAD (CAD group) and 158 patients without CAD. The healthy subjects
      and patients without angiographic evidence of CAD constituted the control group.
      Three polymorphisms were studied: an insertion/deletion (I/D) polymorphism of the
      ACE gene and the T174 M and M235T polymorphisms of the AGT gene. No association
      was found between any of the three studied polymorphisms and the risk of CAD or
      MI in Chinese using univariate or multivariate analysis. In multivariate
      analysis, the relative risks were 1.20 (95% confidence interval = 0.91-1.61, P =
      0.20) for the DD genotype, 1.05 (95% CI = 0.82-1.35, P = 0.69) for the T174
      homozygote, and 1.19 (95% CI = 0.91-1.55, P = 0.20) for the T235 homozygote.
      Similarly, no significant difference was found in the frequencies of the DD
      genotype and the T174 and T235 homozygotes between the control group, the CAD
      group, the non-MI group, and the MI group when analyzed according to sex, age, or
      degree of risk. Our data suggest that neither the DD genotype of the ACE I/D
      polymorphism nor the T174 and T235 homozygotes of the AGT gene confer significant
      risk for CAD or MI in Chinese.

PMID- 9254852
TI  - Human fibroblast growth factor receptor 3 gene (FGFR3): genomic sequence and
      primer set information for gene analysis.
AB  - We have determined the nucleotide sequence of the human fibroblast growth factor
      receptor 3 (FGFR3) gene, including 800 bp of the 5'-flanking region and compared
      the sequence with the previously published murine Fgfr3 gene. The organization of
      the gene is highly conserved between man and mouse. We used the intron sequences
      to design a set of primers that allow amplification of the 17 exons (2-18) that
      encode the complete open reading frame. Using these primers the FGFR3 gene can be
      amplified at the genomic level, which significantly facilitates mutational
      screening.

PMID- 9254853
TI  - A new mutation, 3905insT, accounts for 4.8% of 1173 CF chromosomes in Switzerland
      and causes a severe phenotype.
AB  - We have analysed 1173 cystic fibrosis (CF) chromosomes from Switzerland for eight
      mutations in the CF transmembrane conductance regulator (CFTR) gene. This
      permitted the identification of 88.5% of all mutations present. A novel insertion
      mutation in exon 20 of the CFTR gene, 3905insT, was discovered. This mutation
      accounted for 4.8% of CFTR gene mutations in Switzerland and has since been
      identified in other populations of probable Swiss descent. It is associated with
      a highly variable clinical phenotype but always with pancreatic insufficiency.
      Haplotype analysis with three intragenic microsatellites in the CFTR gene showed
      that the mutation is associated with a haplotype rarely identified on other CFTR
      alleles and, therefore, that the frequency of the mutation in Switzerland is
      explained by a founder effect of a relatively recent mutation event.

PMID- 9254854
TI  - Molecular genetic analysis of the FMR-1 gene in a large collection of autistic
      patients.
AB  - A genetic etiology in autism is now strongly supported by family and twin
      studies. A 3:1 ratio of affected males to females suggests the involvement of at
      least one X-linked locus in the disease. Several reports have indicated an
      association of the fragile X chromosomal anomaly at Xq27.3 (FRAXA) with autism,
      whereas others have not supported this finding. We have so far collected blood
      from 105 simplex and 18 multiplex families and have assessed 141 patients by
      using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic
      Observation Scale, and psychometric tests. All four ADI-R algorithm criteria were
      met by 131 patients (93%), whereas 10 patients (7%) showed a broader phenotype of
      autism. Southern blot analysis was performed with three different enzymes, and
      filters were hybridized to an FMR-1-specific probe to detect amplification of the
      CCG repeat at FRAXA, to the complete FMR-1 cDNA probe, and to additional probes
      from the neighborhood of the gene. No significant changes were found in 139
      patients (99%) from 122 families, other than the normal variations in the
      population. In the case of one multiplex family with three children showing no
      dysmorphic features of the fragile X syndrome (one male meeting 3 out of 4 ADI
      algorithm criteria, one normal male with slight learning disability but negative
      ADI-R testing, and one fully autistic female), the FRAXA full-mutation-specific
      CCG-repeat expansion in the genotype was not correlated with the autism
      phenotype. Further analysis revealed a mosaic pattern of methylation at the FMR-1
      gene locus in the two sons of the family, indicating at least a partly functional
      gene. Therefore, we conclude that the association of autism with fragile X at
      Xq27.3 is non-existent and exclude this location as a candidate gene region for
      autism.

PMID- 9254855
TI  - Implications of intragenic marker homozygosity and haplotype sharing in a rare
      autosomal recessive disorder: the example of the collagen type XVII (COL17A1)
      locus in generalised atrophic benign epidermolysis bullosa.
AB  - Generalised atrophic benign epidermolysis bullosa (GABEB) is a form of junctional
      epidermolysis bullosa with a recessive mode of inheritance. The gene considered
      likely to be involved in this disease is COL17A1, since in the majority of GABEB
      patients the product of that gene, the 180-kD bullous pemphigoid antigen (BP180),
      is undetectable in skin. We have identified an intragenic COL17A1 microsatellite
      marker for which 83% of randomly selected control individuals are heterozygous.
      We observed homozygosity for different alleles of this marker in five out of six
      collagen type XVII-negative GABEB patients of different European descent. Five of
      the six COL17A1 alleles of three patients originating from the eastern part of
      the Netherlands were identical, as were the haplotypes including flanking
      markers. The 2342delG mutation was identified in all these five alleles. This
      confirms the expectation that due to genetic drift and hidden inbreeding for an
      autosomal recessive disorder with low gene frequency, such as collagen type XVII
      negative GABEB, most disease alleles from a restricted geographical area will be
      "identical by descent". Our results demonstrate that involvement of a candidate
      gene can be confirmed by looking for identity by descent of highly informative
      intragenic markers.

PMID- 9254856
TI  - FISH-deletion mapping defines a 270-kb short stature critical interval in the
      pseudoautosomal region PAR1 on human sex chromosomes.
AB  - Deletions of the pseudoautosomal region (PAR1) of the sex chromosomes have
      recently been discovered in individuals with short stature, and a minimal common
      deletion region of 700 kb within PAR1 has subsequently been defined. We have
      cloned this entire region, which is bounded by the Xp/Yp telomere, as an
      overlapping cosmid contig. In the present study, we have used fluorescence in
      situ hybridization (FISH) to study four patients with X-chromosomal
      rearrangements, two with normal height and two with short stature. Genotype
      phenotype correlations have narrowed down the the critical "short stature
      interval" to a 270-kb region containing the gene with an important role in
      growth. A minimal tiling path of 6-8 cosmids bridging this interval is now
      available for interphase and metaphase FISH and provides a valuable tool for
      diagnostic investigations of patients with idiopathic short stature.

PMID- 9254857
TI  - Evidence for balancing of KM, but not GM, alleles by heterotic advantage in South
      Amerinds.
AB  - Two KM alleles occur in 1075 South Amerinds of 14 tribes in approximately
      balanced and uniform frequency. However, the number of heterozygotes is 12.7%
      greater than expected by frequency analysis and 16.5% greater by segregation
      analysis. This excess is evident in children 0-4 years of age and may reflect
      either prenatal or early childhood selection. The frequencies of GM haplotypes
      were different, and quite uniformly so, in diverse tribes. Most GM heterozygotes
      can only be distinguished from GM 1,2,17 21 homozygotes by DNA or family
      relationship. No deficit of GM homozygotes was observed in 119 children in whom
      heterozygosis was determined by family. Thus, the KM polymorphism, like HLA, may
      be maintained by preferential survival of heterozygotes, but GM probably depends
      on another mechanism.

PMID- 9254858
TI  - Polymorphism in exon 10 of the human coagulation factor V gene in a population at
      risk for sickle cell disease.
AB  - In Caucasians, the R506Q mutation in exon 10 of the factor V gene (FV Leiden)
      confers an increased risk of thromboembolism. We have scanned this region of the
      gene for possible mutations in 450 subjects from populations at risk for sickle
      cell disease (SCD). The R506Q mutation was absent in subjects from sub-Saharan
      Africa, whereas its allelic frequency was 2.5% in the West Indies. Only one other
      substitution with no functional consequences in vitro (R485K) was found (32.4%
      allelic frequency) in sub-Saharan Africa. Thus, we found no mutations in exon 10
      of the FV gene constituting an additional risk factor for thrombosis in SCD in
      sub-Saharan Africa. This suggests that the putative selective advantage conferred
      by R506Q does not exist in these populations, unless R485K has functional
      consequences in vivo. If further suggests that R506Q in American Africans is of
      Caucasian origin. Our data are the first to document ethnic variations in the
      frequency of the R485K polymorphism.

PMID- 9254859
TI  - Evidence for gene conversion in the generation of extensive polymorphism in the
      promoter of the growth hormone gene.
AB  - The human growth hormone gene (GH-N) is located in a cluster of five highly
      homologous genes that are coordinately expressed in pituitary (GH-N) and in
      placental tissues (the chorionic-somatomammotropin-like gene, the GH-variant gene
      and the two chorionic somatomammotropin genes). Sequence analysis from position 
      162 to position +100 of the GH-N gene has revealed eight nucleotide polymorphisms
      with no significant difference in frequency between patients affected by isolated
      growth hormone deficiency and controls. Remarkably, all these variations are
      located at positions where the GH-N differs from at least one of the other four
      homologous genes. The analysis of the twelve GH-N haplotypes originating from the
      combinations of the eight polymorphisms has revealed that not only single
      variations, but also nucleotide combinations are identical to those of the other
      placental genes. These findings suggest that whole stretches of the GH-N gene
      promoter have been replaced by homologous DNA stretches copied from one of the
      other four loci by repeated gene-conversion-like events, where the GH-N gene has
      acted as the recipient and the placental genes as donors of the converted
      sequences. The presence of a Chi-like element also indicates that the GH-N
      promoter represents a hot spot of gene conversion. Three of these variations
      cause, in addition, an amino-acid substitution in the GH-gene-derived
      transcriptional activator gene whose coding sequence overlaps the GH-N promoter.
      Thus, a DNA region that serves two distintic functions representing the proximal
      promoter of a gene and the 5' coding region of another gene displays an unusually
      high degree of polymorphism that has probably arisen because of gene conversion.

PMID- 9254860
TI  - Deletions in Xq26.3-q27.3 including FMR1 result in a severe phenotype in a male
      and variable phenotypes in females depending upon the X inactivation pattern.
AB  - High resolution cytogenetics, microsatellite marker analyses, and fluorescence in
      situ hybridization were used to define Xq deletions encompassing the fragile X
      gene, FMR1, detected in individuals from two unrelated families. In Family 1, a
      19-year-old male had facial features consistent with fragile X syndrome; however,
      his profound mental and growth retardation, small testes, and lover limb skeletal
      defects and contractures demonstrated a more severe phenotype, suggestive of a
      contiguous gene syndrome. A cytogenetic deletion including Xq26.3-q27.3 was
      observed in the proband, his phenotypically normal mother, and his learning
      disabled non-dysmorphic sister. Methylation analyses at the FMR1 and androgen
      receptor loci indicated that the deleted X was inactive in > 95% of his mother's
      white blood cells and 80-85% of the sister's leukocytes. The proximal breakpoint
      for the deletion was approximately 10 Mb centromeric to FMR1, and the distal
      breakpoint mapped 1 Mb distal to FMR1. This deletion, encompassing approximately
      13 Mb of DNA, is the largest deletion including FMR1 reported to date. In the
      second family, a slightly smaller deletion was detected. A female with moderate
      to severe mental retardation, seizures, and hypothyroidism, had a de novo
      cytogenetic deletion extending from Xq26.3 to q27.3, which removed approximately
      12 Mb of DNA around the FMR1 gene. Cytogenetic, and molecular data revealed that
      approximately 50% of her white blood cells contained an active deleted X. These
      findings indicate that males with deletions including Xq26.3-q27.3 may exhibit a
      more severe phenotype than typical fragile X males, and females with similar
      deletions may have an abnormal phenotype if the deleted X remains active in a
      significant proportion of the cells. Thus, important genes for intellectual and
      neurological development, in addition to FMR1, may reside in Xq26.3-q27.3. One
      candidate gene in this region, SOX3, is thought to be involved in neuronal
      development and its loss may partly explain the more severe phenotypes of our
      patients.

PMID- 9254861
TI  - Identification of a four-base deletion (delTCAT296-299) in the dihydropyrimidine
      dehydrogenase gene with variable clinical expression.
AB  - Dihydropyrimidine dehydrogenase catalyzes the first and rate-limiting step in the
      breakdown of thymine, uracil, and the widely used antineoplastic drug, 5
      fluorouracil. Sequence analysis of the dihydropyrimidine dehydrogenase cDNA in a
      Dutch consanguineous family identified a novel four-base deletion (delTCAT296
      299) leading to premature termination of translation. The deletion is located in
      a TCAT tandem-repeat sequence and most likely results from unequal crossing-over
      or slipped mispairing. In this family we identified three homozygous individuals
      for this mutation. Two of these showed convulsive disorders but one was
      clinically normal. This observation suggests that, at least in this family, there
      is no clear correlation between the dihydropyrimidine dehydrogenase genotype and
      phenotype.

PMID- 9254863
TI  - Toward a multicolor chromosome bar code for the entire human karyotype by
      fluorescence in situ hybridization.
AB  - A colored banding pattern for human chromosomes is described that distinguishes
      each chromosome in a single fluorescence in situ hybridization with a set of
      subregional DNA probes. Alu/polymerase chain reaction products of various
      human/rodent somatic cell hybrids (fragment hybrids) were pooled into two probe
      sets that were labeled differentially and detected by red and green fluorescence.
      Chromosome regions hybridized by DNA present in both pools appeared yellow. The
      result was a multi-color set of 110 distinct signals per haploid chromosome set
      for the human karyotype. Each individual chromosome showed a unique sequence of
      signals, a result termed the "chromosome bar code". The reproducibility of the
      hybridization pattern in various labeling and hybridization experiments was
      analyzed by computer densitometry. We have applied the chromosome bar code both
      in diagnostic cytogenetics and in genome studies. The approach allows the rapid
      identification of chromosomes and chromosome rearrangements. Although not yet
      showing the resolution of classical banding patterns, the present experiments
      demonstrate various applications in which the present multi-color bar code can
      significantly add to the spectrum of cytogenetic techniques.

PMID- 9254862
TI  - Mutational and genetic origin of LDL receptor gene mutations detected in both
      Belgian and Dutch familial hypercholesterolemics.
AB  - DNA samples from 100 unrelated Belgian patients with familial
      hypercholesterolemia (FH) were screened for the presence of specific low-density
      lipoprotein receptor (LDLR) gene mutations, previously shown to be prevalent in
      related populations. Two point mutations, viz., P664L and a G to A splicing
      defect at position 1359-1, were detected in single Flemish-speaking families. A
      long-distance polymerase chain reaction (PCR) assay, used to screen for the 4-kb
      and 2.5-kb deletions previously identified by Southern blot analyses in different
      parts of The Netherlands, revealed a 3-kb deletion in two Belgian patients.
      Comparison of PCR product length showed that both Dutch deletions of exons 7-8
      are identical to that found in Belgians, but different from the 2.5-kb deletion
      previously described in South Africans of mixed ancestry. The Belgian patients
      probably share a common ancestor, for each mutation identified, with FH patients
      from The Netherlands, since all three mutations were associated with the same
      LDLR gene haplotype as described for the Dutch population. Analysis of the
      deletion junctions demonstrated the role of a 31-bp repetitive sequence in the
      generation of large rearrangements involving exons 7 and 8 of the LDLR gene. The
      finding that only 4 out of 100 analyzed Belgian hypercholesterolemics carry a
      known LDLR mutation that is prevalent in related populations suggests that the
      Belgian FH population has its own spectrum of mutations.

PMID- 9254865
TI  - Exon skipping in the sterol 27-hydroxylase gene leads to cerebrotendinous
      xanthomatosis.
AB  - We report a new mutation in the sterol 27-hydroxylase (CYP 27) gene in a Dutch
      family with cerebrotendinous xanthomatosis: a G-->A transition in the splice
      donor site in intron 4. This mutation leads to skipping of exon 4, resulting in a
      loss of 66 amino acids in the CYP 27 enzyme molecule.

PMID- 9254864
TI  - Cystic fibrosis in Lebanon: distribution of CFTR mutations among Arab
      communities.
AB  - Cystic fibrosis (CF) is thought to be rare among the Arab populations from the
      Middle East and little data have been reported so far. We have studied a sample
      of 20 families living in Lebanon for several generations and who have at least
      one child with CF. These families are mainly from the Maronite, Greek Catholic,
      Greek Orthodox. Shiite or Sunnite groups. We found a 50% rate of consanguineous
      marriage, independent of the community of origin. The distribution of CF
      genotypes was determined through the screening of all exons of the CFTR (cystic
      fibrosis transmembrane conductance regulator) gene by the technique of denaturing
      gradient gel electrophoresis combined with asymmetric amplification DNA
      sequencing. A total of ten different mutations accounting for 87.5% of 32
      unrelated CF alleles was identified, including two novel putative mutations
      (E672del and IVS21-28G-->A). Three mutations, delta F508 (37.5%), W1282X (15.6%),
      and N1303K (9.4%) accounted for 62.5% of CF alleles. Interestingly, in the
      Maronite group, 66.7% of the delta F508 chromosomes were found to be associated
      with allele 7 of the IVS8(T)tract, contrasting with the absolute linkage
      disequilibrium between European delta F508 chromosomes and allele 9. During this
      study, two previously undescribed polymorphisms (IVS14a + 17del5 and 2691T/C)
      were also identified.

PMID- 9254866
TI  - Evidence of a third locus in X-linked recessive spastic paraplegia.
AB  - We have investigated a family with severe X-linked spastic paraplegia and
      assigned the disease locus to Xq11.2-q23 by linkage and haplotype analysis. This
      region harbors the gene coding for proteolipid protein, which is mutated in one
      of the two established forms of X-linked spastic paraplegia, i.e., SPG2. We have
      performed extensive mutation analysis of this gene. Our failure to detect a
      mutation in this family suggests a third locus in X-linked recessive spastic
      paraplegia.

PMID- 9254867
TI  - Collagen subtype pattern in normal and varicose saphenous veins in humans.
AB  - Our present study was to determine the collagen subtype pattern in the greater
      saphenous vein of the lower limb, obtained from 21 normal (macroscopically and
      ultrastructurally non-varicose vein segments from non-varicose subjects) and 37
      varicose subjects, and to compare affected (macroscopically and ultrastructurally
      varicose segments from varicose veins) vs. non-affected (macroscopically and
      ultrastructurally non-varicose segments from varicose veins) segments (16). After
      elastase pretreatment and partial pepsin digestion, types I, III & V collagens
      (CI, CIII, CV) were extracted selectively by differential salt precipitation and
      measured quantitatively in samples obtained from normal and varicose saphenous
      veins-either affected or unaffected segments. Significant elevations of water (p
      < 0.05) and collagen type I [CI] (p < 0.01) content in varicose veins (both
      affected and unaffected segments) as compared with normal saphenous veins were
      observed. The collagen type III (CIII) and collagen type V (CV) content of
      varicose veins were found to be slightly reduced as compared to normal veins and
      consequently the CI/(CIII+CV) ratio in varicose veins increased significantly (p
      < 0.02) as compared to normal veins. Elevation of the CI/(CIII+CV) ratio in
      varicose veins may cause considerable weakening of the venous wall, further
      supporting the "weak wall" theory of varicose vein etiology.

PMID- 9254868
TI  - The value of anti-Helicobacter pylori IgG antibodies in establishing eradication
      of infection in children.
AB  - The aim of this study was to evaluate the performance of anti-Helicobacter pylori
      (H. pylori) IgG antibodies in monitoring eradication of infection in children.
      Forty-seven H. pylori-infected children (aged 12.5 +/- 3.0 years, range 6.5-18
      years) were followed for a mean of 30.3 months (range 6.66 months). Patients were
      divided into those with eradicated infection and those with ongoing infection, as
      determined by antral biopsy-related tests (histology, urease and culture). Anti
      H. pylori antibodies (EIA) were tested at diagnosis and follow-up and changes of
      antibody titers were compared between the two groups. Twenty-five of 26 non
      eradicated patients showed persistently high levels of antibodies throughout the
      study. One patient had non-detectable antibodies despite an ongoing infection for
      12 months. Patients with eradicated infection showed a progressive fall of
      antibody levels from 52.9 +/- 32.4 U/ml at diagnosis to 17.5 +/- 4.1 U/ml at 6
      months (p < 0.007) and 4.4 +/- 0.7 U/ml at > or = 12 months (p < 0.002). In 17 of
      21 eradicated patients, serum antibodies normalized during the follow-up period;
      in 4 of the 21 patients, a decrease of > or = 40% of the initial value was
      observed during the 8-month follow-up. The validity of serology in the evaluation
      of H. pylori infection had a sensitivity of 100%, specificity of 96% and positive
      predictive and negative predictive values of 95% and 100% respectively. Our
      conclusion is that serial determination of anti-H. pylori antibodies is a
      reliable method for the follow-up and monitoring of H. pylori eradication in
      children and adolescents.

PMID- 9254869
TI  - Evaluation of febrile infants under 3 months of age: is routine lumbar puncture
      warranted?
AB  - Fever may be the sole clinically evident presentation of serious bacterial
      infection (SBI) in a very young infant, and therefore lumbar puncture is still
      widely regarded as a mandatory procedure in the sepsis workup of febrile infants
      under 2 months of age. In this retrospective study, we evaluated the frequency
      and the diagnostic value of cerebrospinal fluid examination in 492 infants aged
      less than 3 months who were hospitalized because of fever during 1988-1994. The
      patients were categorized as being at "high risk" or "low risk" for SBI according
      to current clinical and laboratory criteria. Among the 492 infants, 196 (40%)
      were identified as "high-risk" for SBI, and 296 (60%) were at low risk. Among the
      overall series of infants, 60 babies (12%) were subsequently proven with
      bacterial infection. Among the 196 "high-risk" babies, 26% had bacterial
      infection, compared to only 3% of the 296 infants at low risk (p < 0.0001),
      denoting a sensitivity of 85% and a specificity of 65% of the clinical
      classification criteria. Lumbar puncture was done to 186 (46%) infants upon
      hospital admission; 176 punctures yielded satisfactory samples of cerebrospinal
      fluid (CSF). Sixteen (3%) patients had abnormal CSF findings: 2 of them had
      positive bacterial cultures and 14 were compatible with aseptic meningitis. The 2
      patients with purulent meningitis were clinically very ill and were immediately
      recognized as deserving a lumbar puncture. Of the 14 patients with aseptic
      meningitis, 13 were initially screened as being at high risk for serious
      infection, and therefore underwent a lumbar puncture. Over the years of this
      survey, a declining trend for performing lumbar puncture in "low-risk" young
      febrile infants became evident: during 1988-1992, evaluation of sepsis included a
      lumbar puncture in 45% of the infants, compared to 27% during the following 2
      years (p < 0.0001). Not one instance of purulent meningitis evolved among the
      infants in whom lumbar puncture was not performed. Our observations suggest that
      hospitalized young febrile infants may safely be spared a lumbar puncture when
      they do not meet the proposed criteria for being at high risk, or when their
      clinical and laboratory picture suggests being at low risk for SBI.

PMID- 9254870
TI  - Chlamydia trachomatis infection during pregnancy: can it cause an intrauterine
      infection?
AB  - In an attempt to prove the presence of intrauterine fetal chlamydial infection,
      sera from 26 laboring women, who tested positive for cervical chlamydial antigen
      in the first half of their pregnancies, and from 43 laboring women with no
      evidence of such infection, and sera from the cord of their delivered infants
      were tested for chlamydial IgA-, IgG- and IgM-specific antibodies. Nine (34.6%)
      of the 26 women with positive cervical infection and 5 (11.6%) of the 43 women
      with no identifiable cervical infection had significant antibody levels at the
      time of the delivery. Three of the 26 (11.5%) babies born to the mothers with
      positive cervical chlamydial infection early in the pregnancy and high antibody
      titer at delivery were found to have anti-chlamydial antibodies in their cord
      serum, indicating intrauterine infection; cord sera from the other 43 babies were
      negative for these antibodies. These findings suggest a low but possible risk of
      intrauterine infection in the presence of lower genital infection during
      pregnancy.

PMID- 9254871
TI  - Compliance with mammography screening in Israeli women: the impact of a pre
      scheduled appointment and of the letter-style.
AB  - The objectives of this study were to determine the impact of different personal
      invitations on screening mammography attendance and to clarify the influence of
      personal characteristics and health-related attitudes and behaviors on
      compliance. One thousand and five hundred women, aged 50-74 years, were randomly
      selected in the city of Haifa. Four letters of invitation were used. Actual
      mammography performance was validated by a national computerized database. All
      other data was collected via a telephone interview following the mammography. The
      overall compliance rate amounted to 45%. The major predictors of compliance were
      having had a clinical breast examination within the previous year (p = 0.0008),
      having a health professional recommend routine mammography (p = 0.01) and
      perceiving mammography as efficient in early detection of breast cancer (p =
      0.02). Aggressiveness of message details, or a family physician's or higher
      authority's signature on the letter had no impact on compliance. A letter of
      invitation for a routine mammogram at a specific time resulted in an overall rate
      of compliance 3-fold higher than the baseline. Based on the results of this
      study. Kupat Holim Clalit decided to implement use of personal invitations for
      screening mammography to israeli women on a regular basis.

PMID- 9254872
TI  - Radiofrequency catheter ablation of ectopic atrial tachycardia.
AB  - Ectopic atrial tachycardia (EAT) is an uncommon type of supraventricular
      tachycardia. It is usually chronic, incessant and resistant to pharmacologic
      therapy. Radiofrequency catheter ablation, which has become one of the treatments
      of choice for the more common types of supraventricular tachycardia, has recently
      also been shown to be effective in EAT. Radiofrequency catheter ablation was
      attempted in three patients with incessant EAT. Two of the patients, aged 7 and
      13 years, had signs of left ventricular dysfunction, and the EAT originated in
      the left atrium. The remaining patient, aged 72 years, had a right EAT with
      normal left ventricular function. Radiofrequency ablation was guided by
      endocardial atrial mapping to locate the site of earliest atrial activation.
      Ablation was successful in all three patients, with complete cure of the
      tachycardia for a follow-up period of 12 to 19 months. Radiofrequency catheter
      ablation of EAT is highly successful and should be considered as one of the
      treatments of choice for this arrhythmia.

PMID- 9254873
TI  - Height and social class in male adolescents from different ethnic backgrounds in
      Israel.
AB  - The relationship between height and social class, independent of the effect of
      ethnic background was examined. This is a population-based study of 17-year-old
      israeli-born Jewish males born between 1966-1969 who underwent routine physical
      examination prior to army recruitment. Inductees descending from 9 ethnic
      backgrounds-Germany, Hungary, India, Morocco, Poland, Romania, Russia, Yemen and
      at least 3rd-generation israeli-born were used for this analysis. Anthropometric
      data was abstracted from the computerized induction examination; socioeconomic
      status (SES) was assigned according to the residence of each recruit. Statistical
      analysis included analysis of variance and chi square test for linear trend. Mean
      height of the total (reference) group was 173.7 cm, ranging from 172.0 cm in the
      lowest SES level to 175.1 cm in the highest level. The proportion of individuals
      above the 85th percentile of height of the reference group, increased linearly
      from 8.7% (lowest SES) to 18.5% (highest SES) (p < 0.01). The mean height of
      recruits differed considerably among ethnic groups in each SES level and ranged
      from 170.8 cm (Yemenites) to 175.4 cm (Russian and Romanian) in the total group.
      In each ethnic group, height differences between extreme levels of SES were
      observed ranging from 2.3 cm (Morocco) to 4.3 cm (Russia). We conclude that
      height among 17-year old israeli-born males is positively associated with SES
      after controlling for ethnicity.

PMID- 9254874
TI  - Reported health concerns of Israeli high school students--differences by age and
      sex.
AB  - Health concerns of high school students in the 10th grade and again in the 12th
      grade were studied. The students filled out an anonymous questionnaire that
      included a list of 73 concerns. At both ages their main concerns were reportedly
      related to school. Concerns relating to army service ranked high particularly in
      the 12th grade, among both sexes. Concerns relating to sexual relations were
      frequent among boys at both ages, whereas concerns about mood and loneliness were
      more frequent among girls. Reports on physical concerns were frequently related
      to height among the younger boys and weight and diet among girls of both ages.
      Concerns were grouped into 6 domains. In each of them, except for sexuality,
      girls had more concerns. A significant decline in the number of concerns was
      noted from the first to the second survey, indicating a partial resolution of the
      issues central to adolescent development. Knowledge about concerns of adolescents
      may help health care providers in counseling and health education program
      planning.

PMID- 9254875
TI  - The role of botulinum toxin in the treatment of lower limb spasticity in children
      with cerebral palsy--a pilot study.
AB  - The use of botulinum toxin in cerebral palsy is still experimental. We conducted
      a pilot clinical trial with botulinum toxin injections on 14 children with
      spastic cerebral palsy. All patients were mobile with dynamic contractures of the
      gastrocnemius-soleus muscles. The injections were monophasic in 9 patients and
      biphasic in 5 patients. Improvement in dorsiflexion, quality of gait and grade of
      independence were achieved in 3 patients; improvement in dorsilflexion and
      quality of gait were achieved in 6 patients. There was no significant change in
      quality of gait in 4 patients. The beneficial effect lasted 4-9 months (mean 6.7
      months). A combined functional score given by the physicians, therapists and
      parents showed a marked improvement in 6 patients (42.9%), a mild improvement in
      3 patients (21.4%) and no improvement in 5 patients (35.7%). Biphasic injections
      were slightly more effective than monophasic injections (p < 0.02). Adverse
      effects were usually mild. We conclude that botulinum toxin may be used for the
      reduction of spasticity in patients with cerebral palsy who have dynamic
      deformities of the ankle joints.

PMID- 9254876
TI  - Hemodialysis treatment may improve inspiratory muscle strength and endurance.
AB  - Chronic renal failure can result in a variety of conditions leading to muscle
      weakness. However, little is known about inspiratory muscle performance and the
      acute effects of hemodialysis on the muscles. We investigated the inspiratory
      muscle performance in chronic renal failure patients undergoing maintenance
      dialysis. Static inspiratory pressures and inspiratory muscle endurance were
      determined in 21 patients (13 men and 8 women), before and after dialysis.
      Inspiratory muscle strength before dialysis was significantly reduced in all
      subjects but one (mean +/- SEM, PImax = 52.9% of predicted). Following dialysis,
      the static inspiratory pressure was increased in 18 patients, decreased in 1
      patient and remained unchanged in 2. Inspiratory muscle endurance was almost
      normal before dialysis (mean +/- SEM, PmPeak/PImax = 66.1%). Following dialysis,
      the inspiratory muscle endurance increased in 13 patients, decreased in 5
      patients and remained unchanged in 3. There was no significant correlation
      between inspiratory muscle strength and the time on chronic hemodialysis. We
      conclude that in patients with chronic renal failure receiving maintenance
      hemodialysis there is predialysis reduction in inspiratory muscle strength and
      less significant reduction in the endurance. Both the inspiratory muscle strength
      and endurance significantly increased following hemodialysis in most but not all
      of the subjects. The dialysis-induced changes in biochemical parameters may exert
      opposing effects on inspiratory muscle performance. This might explain the
      diversity of the results obtained in this study and studies performed by others.

PMID- 9254877
TI  - Planter foot pressures in pregnant women.
AB  - The physiological changes occurring during pregnancy may be responsible for the
      faulty foot position leading to backache and lower limb pain. We evaluated the
      changes in the plantar foot pressures during pregnancy. Twenty-eight, full-term,
      healthy, pregnant women, average age 28 years, were examined and evaluated
      clinically, and the plantar foot pressure distribution was measured statically
      and dynamically using the EMED system. Twenty-eight, non-pregnant women, average
      age 25 years, served as the control group. In the static measurements, the
      pregnant women had significantly lower maximal forefoot pressures and higher
      hindfoot pressures than the non-pregnant women. The area of the foot in contact
      with the measuring pressure plate was greater in the pregnant women than in the
      non-pregnant women. In the dynamic measurements, the maximal force in almost
      every area of interest was significantly higher. The total force exerted on the
      pressure plate at the instant of maximal force of every area of interest during
      the whole step was higher in the pregnant group. On the medial side of the
      forefoot there was a slight decrease in the contact time of the maximal force.
      The peak pressures were higher in the midfoot of both feet and on the lateral
      side of the right forefoot in the pregnant women. In the medial side of the
      forefoot, the peak pressures were lower in pregnant women. CONCLUSIONS: The
      pregnant woman has a different pattern of gait. There is an increase of load on
      the lateral side of the foot and the hindfoot. These changes may be responsible
      for the musculoskeletal complaints of lower limb pain in pregnant women.

PMID- 9254878
TI  - Allergy and SLE: common and variable.
AB  - Autoimmune conditions and allergic diseases are both characterized by immune
      dysregulation. The purpose of this study was to evaluate the incidence of various
      allergic disorders in patients with systemic lupus erythematosus (SLE). Sixty
      patients with SLE completed a questionnaire detailing their allergic disorders,
      which we compared with those of 60 age- and sex-matched healthy people. Forty
      four of the SLE patients (56%) had at least one type of allergic disorder.
      Perturbation of immunoregulation in SLE patients may increase the susceptibility
      to develop IgE-mediated allergic disorders.

PMID- 9254879
TI  - Allergy and systemic lupus.

PMID- 9254880
TI  - The molecular mechanism of aflatoxin B1-induced liver cancer: is mitotic
      recombination involved?

PMID- 9254881
TI  - Expression of HMGI-C, a member of the high mobility group protein family, in a
      subset of breast cancers: relationship to histologic grade.
AB  - The high-mobility-group (HMG) protein gene HMGI-C is apparently involved in the
      genesis of a variety of benign human solid tumors with rearrangements of
      chromosomal region 12q14-15 affecting the HMGI-C gene. So far, no expression of
      HMGI-C has been found in adult tissues, and no data are available on the
      expression of HMGI-C in primary human malignant tumors of epithelial origin.
      Therefore, we analysed the HMGI-C expression patterns in 44 breast cancer samples
      and 13 samples of nonmalignant adjacent tissue by hemi-nested reverse
      transcriptase-polymerase chain reaction for HMGI-C expression. There was no
      detectable expression of HMGI-C in any nonmalignant adjacent breast tissues
      analyzed. In contrast, we found expression in 20 of 44 breast cancer samples
      investigated. In invasive ductal tumors, expression was noted predominantly in
      tumors with high histologic grade: 17 of 21 breast cancer samples with histologic
      grade 3 but only three of 16 samples with histologic grades 1 or 2 showed
      expression of HMGI-C. In addition, all seven lobular breast cancer samples tested
      did not express HMGI-C. From these results, we concluded that HMGI-C expression
      may be of pathogenetic or prognostic importance in breast cancer.

PMID- 9254882
TI  - Effect of 12-O-tetradecanoylphorbol-13-acetate on inhibition of expression of
      keratin 1 mRNA in mouse keratinocytes mimicked by 12(S)-hydroxyeicosatetraenoic
      acid.
AB  - Differentiation of cultured keratinocytes is controlled by the calcium
      concentration of the medium and is marked by the expression of differentiation
      specific keratins. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA)
      alters the normal differentiation program and suppresses keratin (K) 1
      expression. Based on reported similarities in the effects of TPA and the
      arachidonic acid metabolite 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), we
      hypothesized that 12(S)-HETE might suppress K1 expression in mouse keratinocytes.
      We also investigated the effect of pretreatment with 13(S)-hydroxyoctadecadienoic
      acid (13(S)-HODE) because others have reported that 13(S)-HODE prevents 12(S)
      HETE-induced events. In our study, 100 nM 12(S)-HETE mimicked the effect of 500
      nM TPA in suppressing K1 mRNA expression within 24 h of calcium-induced
      differentiation. Pretreatment with 100 nM 13(S)-HODE blocked the 12(S)-HETE
      effect but not the TPA effect. A role for protein kinase C (PKC) was suggested
      for both TPA and 12(S)-HETE based on the loss of response with the PKC inhibitors
      bryostatin-1 or RO-31-8220. Both TPA and 12(S)-HETE stimulated keratinocyte PKC
      activity. Pretreatment with 13(S)-HODE blocked the 12(S)-HETE-induced increase in
      PKC activity. Immunoblotting showed that whereas TPA caused a rapid, partial
      translocation of the PKC alpha isozyme, it had no effect on the distribution of
      PKC delta. Conversely, 12(S)-HETE had no effect on the distribution of PKC alpha
      but caused a complete translocation of PKC delta. Pretreatment with 13(S)-HODE
      prevented 12(S)-HETE-elicited translocation of PKC delta. We conclude that 12(S)
      HETE mimics the effect of TPA on K1 mRNA and that the effect is mediated through
      different isoforms of PKC.

PMID- 9254883
TI  - Metastasis induced by overexpression of p185neu-T after orthotopic injection into
      a prostatic epithelial cell line (NbE).
AB  - Overexpression of p185erbB2/neu has been detected in many adenocarcinomas,
      including prostatic cancer. In this study, a nontumorigenic cell line isolated
      from the rat prostatic epithelium (NbE) transfected with the activated oncogene
      p185neu-T was used to investigate the role of this oncogene in tumor progression.
      When clones overexpressing p185neu-T were injected orthotopically (1.5 to 2 x
      10(6) cells) into the dorsal-lateral prostates of nude mice, prostatic tumors
      were detected in all mice injected and metastasis to the skeletal muscle in the
      rib area in 60-80% of the mice injected. Tumor and metastasis origin was
      confirmed by reselection with G418 and reverse transcriptase-polymerase chain
      reaction. Control cell lines produced no prostatic tumors or metastases.
      Incubation at low density (12500 cells/2 cm2) in serum-free medium revealed that
      clones overexpressing p185neu-T had a higher rate of [3H]thymidine incorporation
      than did control clones on 3, 5, and 7 d after plating (P < or = 0.0001) and
      constitutively overexpressed the 2.6-kb ornithine decarboxylase transcript.
      Additionally, clones overexpressing p185neu-T demonstrated an increased
      expression of epidermal growth factor receptor and p180erbB4, as judged by RNA
      blot analysis. Together these data support the hypothesis that overexpression of
      p185neu-T fosters tumor progression by several pathways, including induction of
      the metastatic cascade, increased proliferative capabilities, and increased
      expression of other members of the erbB2 gene family.

PMID- 9254884
TI  - Dideoxy fingerprinting assay for BRCA1 mutation analysis.
AB  - Since the isolation of BRCA1, the familial breast/ovarian cancer predisposition
      gene, much effort has been invested in characterizing the mutation spectrum. The
      large size of the gene and the wide distribution of its more than 100 mutations
      has increased the challenge of this endeavor such that traditional mutation
      detection techniques are inadequate. We examined the sensitivity of dideoxy
      fingerprinting (DDF), which combine a Sanger sequencing reaction with multiple
      fragment single-strand conformation analysis (SSCA), as a mutation detection
      technique to screen BRCA1. Here we describe the technique and compare its
      sensitivity with that of SSCA in detecting 21 previously described BRCA1 sequence
      variants. All the variants were detected by DDF, but only 17 of 21 (81%) were
      observed by SSCA under standard conditions. Three of four alterations missed by
      SSCA were base substitutions. As a BRCA1 mutation detection technique, DDF was
      more sensitive than SSCA and may prove to be a useful research tool in defining
      the mutation spectrum within this and other genes.

PMID- 9254885
TI  - Involvement of activator protein-1 (AP-1) in induction of apoptosis by vitamin E
      succinate in human breast cancer cells.
AB  - The purpose of this study was to document induction of apoptosis by vitamin E
      succinate (VES; RRR-alpha-tocopheryl succinate) in human breast cancer cells in
      culture and to characterize potential c-jun involvement. VES at 18.8 microM (10
      micrograms/mL) induced DNA synthesis arrest, reduced total cell numbers, and
      induced apoptosis in estrogen receptor-positive and estrogen-responsive MCF-7
      human breast cancer cells. VES at 10 micrograms/mL induced apoptosis in greater
      than 60% of cells within 3 d of treatment. Apoptosis was documented by detection
      of fragmented or condensed nuclei in 4',6-diamindino-2-phenylindole-stained
      cells, detection of terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick-end labeled DNA, and DNA laddering. Analyses of mRNA and protein levels of
      candidate molecules involved in apoptosis showed that MCF-7 cells treated with
      VES exhibited elevated and persistent expression of c-jun. MCF-7 cells stably
      transfected with a dominant-negative interfering mutant c-jun, TAM-67, and
      expressing high levels of mutant jun exhibited approximately 50% blockage of VES
      mediated apoptosis. In addition to increased c-jun expression after VES
      treatment, VES-treated MCF-7 cells exhibited elevated activator protein-1 (AP-1)
      binding activity. Comparisons of AP-1 binding factors by super-shift analyses
      with jun-specific antibodies in cells sensitive to VES-induced apoptosis (empty
      vector control 7-1 cells) and cells resistant to VES-induced apoptosis (TAM-67
      containing TAM-9 cells) showed that the sensitive cells expressed c-jun and jun D
      and the resistant cells TAM-67 AP-1 binding proteins after VES treatment. These
      studies suggested that c-jun may be involved in the apoptotic process initiated
      by VES treatment of human MCF-7 breast cancer cells.

PMID- 9254886
TI  - Differential effects of p53 mutants on the growth of human bronchial epithelial
      cells.
AB  - We investigated the effects of five different p53 mutants on the growth of
      primary cultures of normal human bronchial epithelial (NHBE) cells. The five
      defective viral pZIP-Neo constructs contained the following mutations at
      mutational hot-spots found in human cancers: codons 143ala, 175his, 248trp,
      249ser, and 273his. NHBE cells were infected with the p53 mutants, wild-type p53,
      or the pZIP-Neo vector control. The 143ala, 248trp, and 273his mutants, as well
      as wild-type p53, decreased the colony-forming efficiency and inhibited the
      growth of NHBE cells. The 175his mutant did not significantly change the growth
      rates. In NHBE cells from three donors, the 249ser mutant conferred a substantial
      growth advantage to the NHBE cells in a colony-forming-efficiency assay. In NHBE
      cells isolated from one donor, the 249ser mutant also produced a significant life
      span extension. These cells grew rapidly through 80 population doublings and
      entered an apparent "crisis" in passage 14. Karyotypic analyses of one culture at
      multiple passages revealed aneuploid populations with alterations of chromosomes
      5, 11, and 13; quantitative DNA analysis detected aneuploidy in late passages
      from that culture and two other primary cultures. These data demonstrated that
      the codon 249ser mutation could provide a growth advantage to bronchial
      epithelial cells and suggest that this mutant protein can induce genomic
      instability.

PMID- 9254887
TI  - A dominant negative mutant of jun blocking 12-O-tetradecanoylphorbol-13-acetate
      induced invasion in mouse keratinocytes.
AB  - We previously reported that induced activator protein-1 (AP-1) transcriptional
      activity appears to be required for tumor promoter-induced transformation in
      mouse epidermal JB6 cells. To extend this investigation to a keratinocyte culture
      model and a transgenic mouse model, we constructed K14TAM67, a keratin 14
      promoter-controlled version of the dominant negative jun mutant to directly block
      AP-1 activity and possibly indirectly block NF kappa B activity in basal squamous
      epithelia. This study was directed at characterizing TAM67 expression and
      biological activity in the mouse cell line 308, a keratinocyte model for studying
      carcinogenesis. Cotransfection of K14TAM67 with luciferase plasmid reporter DNAs
      produced inhibition of basal and 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced AP-1 and NF kappa B activity but had no effect on p53-dependent
      transcriptional activity. In an in vitro invasion assay, stable expression of
      TAM67 in 308 cells blocked TPA-induced Matrigel invasion. This suggests that
      blocking TPA-induced AP-1- or NF kappa B-regulated gene expression by TAM67
      inhibits TPA-induced progression. Recombinant tissue inhibitor of
      metalloproteinase 1 reduced TPA-induced in vitro invasion, thus implicating
      metalloproteinases at least in part in the transcription factor-dependent
      process. Analysis of mRNA levels for members of the matrix metalloproteinase
      (MMP) family, however, revealed that the expression of any single MMP family
      member did not correlate with regulation of AP-1 or NF kappa B activity. However,
      the combination of substantial levels of mRNA for stromelysin-1, stromelysin-2,
      collagenase, membrane type 1 MMP, and gelatinase A occurred only in TPA-treated
      cells in the absence of TAM67. These results suggest that the action of the
      dominant negative jun mutant on AP-1 and NF kappa B gene regulation results in
      complex alterations in the levels of downstream effector genes, such as the
      metalloproteinases, that effect TPA-induced cellular invasion.

PMID- 9254888
TI  - Altered expression of transforming growth factor-alpha: an early event in renal
      cell carcinoma development.
AB  - Transforming growth factor-alpha (TGF-alpha) is a multifunctional cell regulatory
      protein with a wide range of effects on cell growth and differentiation and has
      been implicated in the neoplastic transformation of a variety of cell types.
      Altered expression of TGF-alpha and its cognate receptor (epidermal growth factor
      receptor) is enhanced in human and rat renal cell carcinomas. The objective of
      the study reported here was to determine whether altered TGF-alpha expression is
      an early or late event in renal tubular oncogenesis. The immunohistochemical
      expression of TGF-alpha was studied in preneoplastic renal tubular lesions in a
      rat model of hereditary renal cell carcinoma. Strong TGF-alpha immunoreactivity
      was present at all stages of renal cell tumor development, including the earliest
      detectable dysplasias. In contrast, the non-neoplastic regenerating tubular
      epithelium of rat degenerative nephropathy did not stain for TGF-alpha, although
      this tissue exhibited a proliferative capacity similar to that observed in the
      dysplastic and neoplastic lesions. This study indicated that altered TGF-alpha
      expression was detectable early in the development of renal cell tumors and may
      be an important feature of the transformed phenotype.

PMID- 9254889
TI  - Review of mutagenicity of monocyclic aromatic amines: quantitative structure
      activity relationships.
AB  - Monocyclic aromatic amines (MAAs) are environmental pollutants. Many of them are
      genotoxic and impose hazards to human health. The mutagenicity of more than 80 of
      these amines was reviewed with primary emphasis on evaluation by the Ames
      Salmonella/microsome testing system. Many amines are mutagenic in Salmonella
      tester strains TA98 and TA100, but S9 mix is required for activity for most of
      the active ones. 2,4-Diaminotoluene, 2,4-diaminoethylbenzene, and a few amines
      containing a nitro-group are direct mutagens. There are several quantitative
      structure-activity relationship (QSAR) models which rationalize mutagenicity of
      many aromatic amines and several parameters, such as the lowest unoccupied
      molecular orbital energy (ELUMO), highest occupied molecular orbital energy
      (EHOMO), and hydrophobicity that are important. What factors determine the
      minimum requirement for the compound to be mutagenic and what factors determine
      the extent of mutagenicity suggest questions for further study.

PMID- 9254890
TI  - On the metabolizing systems for short-term genotoxicity assays: a review.

PMID- 9254891
TI  - The first US National Toxicology Program exercise on the prediction of rodent
      carcinogenicity: definitive results.
AB  - A few years ago, the US National Toxicology Program sponsored an exercise aimed
      at comparing different prediction approaches for carcinogenicity by challenging
      them on a common set of chemicals. The exercise was considered to be sufficiently
      completed when 40 (out of 44) chemicals were actually experimentally tested, and
      the experimental and estimated carcinogenicity were compared. More recently, the
      rodent results for the remaining 4 chemicals have been disclosed, making it
      possible to draw definitive conclusions on the comparative exercise. Having
      analyzed the first subset of results with multivariate statistical methods, we
      present here the analysis of the complete set of results. The present analysis
      also considers aspects (e.g., the complementarity of the different systems in
      identifying the carcinogens), which had not been investigated previously. The
      conclusion of this study were: (a) the expansion of the data base from 40 to 44
      chemicals did not significantly change the results of the exercise; (b) the
      structure-activity approaches generated prediction profiles different from those
      generated by the prediction systems mainly relying on the use of experimental
      data (in vitro and in vivo); (c) the performance of the predictive systems was
      generally rather limited; (d) the prediction systems were affected by over
      sensitivity; they were generally capable of identifying the molecules containing
      the potentially alerting substructures, but were not so refined as to be able to
      discriminate between potential and actual carcinogenicity; (e) the combination of
      the systems into batteries did not permit a significant increase in the
      performance of the individual methods. The need for, and possible approaches to
      finely tuning the systems are discussed.

PMID- 9254892
TI  - Mutagenicity, carcinogenicity and teratogenicity of thallium compounds.
AB  - The paper reviews the information available concerning the mutagenic,
      carcinogenic and teratogenic effects of thallium. Data on mutagenic and
      carcinogenic risks of thallium and its compounds are extremely scanty but what is
      available does not indicate that thallium could be mutagenic or carcinogenic. At
      any rate, such risks, if they exist, would be submerged by the general high
      toxicity of thallium. On the other hand, thallium has some teratogenic
      properties, especially on cartilage and bone formation, although this seems to be
      more prominent in chicks than in mammals. Nevertheless, pregnant women should not
      be exposed to doses of thallium which might produce toxic symptoms; exposure to
      lower doses such as might occur near thallium-emitting plants is probably not
      embryotoxic.

PMID- 9254893
TI  - Antimutagenicity of the porphyrins and non-enzyme porphyrin-containing proteins.

PMID- 9254894
TI  - Pharmacological and molecular evidence for the expression of the two steroid 5
      alpha-reductase isozymes in normal and hyperplastic human prostatic cells in
      culture.
AB  - BACKGROUND: Whereas the embryological development of the human prostate is
      clearly dependent on steroid 5 alpha-reductase (5 alpha-R) type 2 expression, the
      respective expression of the two known isoforms (types 1 and 2) of 5 alpha-R in
      the adult human prostate remains unclear. METHODS: 5 alpha-R isoform mRNA
      expression (Northern blots and reverse transcriptase-polymerase chain reaction
      [RT-PCR]) and enzyme activity were studied in immortalized epithelial cells (NE)
      and in fibroblasts from normal (NF) or hyperplastic (BPHF) human prostates.
      RESULTS: 5 alpha-R activity (fmol/microgram DNA/hr) was 1.43 +/- 0.5 in NE, 10.7
      +/- 4.7 in NF, and 79 +/- 37 in BPHF. mRNAs for both 5 alpha-R isoforms were
      expressed in the three cell types, as shown by Northern blot and RT-PCR analysis.
      LY306089, a selective 5 alpha-R type 1 inhibitor, strongly inhibited 5 alpha-R
      activity in all cell types (IC50: 10 nM), confirming the predominant expression
      of 5 alpha-R type 1 in these cells. Finasteride, a 5 alpha-R type 2 inhibitor,
      was less efficient (IC50: 45, 35, and 65 nM in NE, NF, and BPHF, respectively).
      In addition, the inhibition by finasteride decreased with serial subculture in NF
      only, suggesting an effect of age in culture on the expression of 5 alpha-R type
      2 in these cells. SKF105657, also a 5 alpha-R type 2 inhibitor, was a poor
      inhibitor in this system. CONCLUSIONS: These studies demonstrate that human
      prostate cells in culture express both isoforms of 5 alpha-R and suggest a
      balance in the expression of the two isoforms as a function of various regulatory
      factors.

PMID- 9254896
TI  - Fine structural studies of induced tumors arising within the prostatic complex of
      Lobund-Wistar rats.
AB  - BACKGROUND: Morris Pollard, Phyllis Luckert, and colleagues have reported the
      occurrence of spontaneously arising tumors of the prostatic complex in aged
      Lobund-Wistar (L-W) rats, and have also shown that the genesis of such tumors may
      be accelerated by means of intravenous administration of methylnitrosourea,
      followed by androgen supplementation. METHODS: Light and electron microscopic
      investigations of the tumors arising under this regime were conducted, with the
      objective of documenting morphological changes attending the transformation
      process; 10 tumor samples were used for the electron microscopic studies.
      RESULTS: All tumors studied were adenocarcinomas arising within the prostatic
      complex of induced animals. These tumors varied in size, degree of
      differentiation, and invasiveness. Foci of prostatic intraepithelial neoplasia
      were noted in light microscopic studies as well. Consistent fine structural
      features exhibited by cells of the induced adenocarcinomas included a large
      nuclear to cytoplasmic ratio; large irregular nuclei with heavily marginated
      chromatin; conspicuous nucleoli; abundant ribosomes and polysomes and a paucity
      of rough endoplasmic reticulum; and numerous cytoplasmic vesicles and lipid
      inclusions. Numerous, short microvilli extended from the cell surface into a
      copious surrounding extracellular matrix. CONCLUSIONS: Thus, these tumors shared
      many of the fine structural features characteristic of the Dunning (rat) and
      human prostatic adenocarcinomas.

PMID- 9254895
TI  - Luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) and bombesin
      antagonist RC-3940-II inhibit the growth of androgen-independent PC-3 prostate
      cancer in nude mice.
AB  - BACKGROUND: Hormones like bombesin (BN)/gastrin-releasing peptide (GRP) and
      luteinizing hormone-releasing hormone (LH-RH) and growth factors such as
      epidermal growth factor (EGF) might be involved in the relapse of prostate cancer
      under androgen ablation therapy. Interference with receptors for BN/GRP, LH-RH,
      or EGF might provide a therapeutic approach to inhibit tumor growth of androgen
      independent prostate cancer. METHODS: LH-RH antagonist Cetrorelix (SB-75) and the
      BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the
      androgen-independent PC-3 human prostate cancer cell line xenografted into nude
      mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP
      and EGF were measured. RESULTS: When the treatment was started, tumor volume in
      all groups was 70-80 mm3. After 4 weeks, tumor volume in the control animals
      injected with saline was 871 +/- 233 mm3 and that of animals treated with
      Cetrorelix only 197 +/- 61 mm3. The BN/GRP antagonist RC-3940-II also
      significantly reduced PC-3 tumor volume in nude mice to 122 +/- 20 mm3. The
      combination of Cetrorelix and RC-3940-II produced no additional inhibition. High
      affinity receptors for EGF were detected in the tumor membranes and their number
      was significantly decreased after administration of Cetrorelix or RC-3940-II.
      CONCLUSIONS: These findings demonstrate that LH-RH antagonists and BN/GRP
      antagonists inhibit the growth of the androgen-independent prostate cancer cell
      line PC-3 in vivo. Both analogs may exert a direct inhibitory effect on tumor
      growth through a down-regulation of EGF receptors.

PMID- 9254897
TI  - On the prediction of the histologic composition of benign prostatic hyperplasia
      based on clinical and MRI parameters.
AB  - BACKGROUND: The histologic composition of prostate adenoma seems related to the
      development of clinical benign prostatic hyperplasia (BPH). Therefore, a new
      noninvasive prediction model as an alternative for biopsies was investigated.
      METHODS: In 19 patients, the data of a routine preoperative workup for
      transurethral resection (TURP) and of an additional MRI-examination were related
      to the results of morphometry on TURP-tissue. RESULTS: Statistical analysis
      identified age of the patient and MRI-volumetrics of the prostate adenoma as best
      predictors of the epithelial fraction, with a 95% confidence interval of at least
      5% (range, 9-14%) (R2 = 50%). CONCLUSIONS: This prediction model is sufficiently
      accurate to categorize a population of patients into histologic subgroups. It
      seems very likely that this method will be of use as an investigative tool in
      medical trials to provide insight into the pathogenesis of clinical BPH and into
      treatment strategies for the individual patient.

PMID- 9254898
TI  - Effect of vitamin C on prostate cancer cells in vitro: effect on cell number,
      viability, and DNA synthesis.
AB  - BACKGROUND: Many studies describe the protective role of vitamin C (ascorbic
      acid) against cancer development and in treatment of established cancer. The
      present study investigated whether ascorbic acid demonstrates a therapeutic
      benefit for prostate cancer. METHODS: Androgen-independent (DU145) and androgen
      dependent (LNCaP) human prostate cancer cell lines were both treated in vitro
      with vitamin C (0-10 mM). Cell counts, cell viability, and thymidine
      incorporation into DNA were determined. RESULTS: Treatment of DU145 and LNCaP
      cells with vitamin C resulted in a dose- and time-dependent decrease in cell
      viability and thymidine incorporation into DNA. Vitamin C induced these changes
      through the production of hydrogen peroxide; addition of catalase (100-300
      units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of
      ascorbic acid. Superoxide dismutase, an enzyme that dismutates superoxide and
      generates hydrogen peroxide, did not prevent decreases in cell number and DNA
      synthesis, suggesting further the involvement of hydrogen peroxide in vitamin C
      induced changes. These results clearly indicate that reactive oxygen species
      (ROS) are involved in vitamin C-induced cell damage. However, that singlet oxygen
      scavengers such as sodium azide and hydroquinone and hydroxyl radical scavengers
      such as D-mannitol and DL-alpha-tocopherol did not counteract the effects of
      ascorbic acid on thymidine incorporation suggests that vitamin C-induced changes
      do not occur through the generation of these ROS. CONCLUSIONS: Vitamin C inhibits
      cell division and growth through production of hydrogen peroxide, which damages
      the cells probably through an as yet unidentified free radical(s)
      generation/mechanism. Our results also suggest that ascorbic acid is a potent
      anticancer agent for prostate cancer cells.

PMID- 9254899
TI  - Plasminogen activator and matrix metalloproteinase production and extracellular
      matrix degradation by rat prostate cancer cells in vitro: correlation with
      metastatic behavior in vivo.
AB  - BACKGROUND: The plasminogen activation (PA) and metalloproteinase (MMP) system
      are involved in tumor cell migration and invasion. METHODS: The proteolytic
      activity of cell lines originating from the rat Dunning R-3327 prostate tumor was
      analyzed by measuring in vitro extracellular matrix degradation, enzyme activity,
      and mRNA levels of enzymes, inhibitors, and receptors, and compared with their
      known metastatic behavior in vivo. RESULTS: Only the highly metastatic sublines
      AT-3, MATLu, and MATLyLu showed a high extracellular matrix degradation mediated
      by urokinase-type plasminogen activator (u-PA). Relatively high levels of u-PA
      were present in the aggressive cell lines. u-PA receptor mRNA was produced in all
      cells, and all but AT-1 produced LDL-receptor-related-protein (LRP) mRNA. t-PA
      mRNA was only found in HIF and MATLu. In gelatin, zymography lysis was observed
      at 72 kD and 74-76 kD in MATLu and MATLyLu cells, respectively. MMP-2 mRNA was
      present in all cell lines except AT-1 and AT-2, and MMP-3 mRNA was present in AT
      2, AT-3, and MATLu. CONCLUSIONS: These in vitro experiments show that in
      different rat prostate cancer sublines, proteolytic activity and u-PA-mediated
      extracellular matrix degradation correlate with their known metastatic behavior
      in vivo.

PMID- 9254900
TI  - Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic
      loss in advanced human prostate cancer.
AB  - BACKGROUND: We recently isolated the KAI1 gene, a metastasis suppressor gene for
      prostate cancer, from human chromosome region 11p13-cen-containing rat prostate
      cancer cells. The present study was performed to further locate the region of the
      KAI1 gene on the short arm of chromosome 11, and to examine whether loss of this
      region is significant during progression of human prostate cancer. METHODS: The
      small portion of human chromosome 11 (i.e., 11p13-cen) was reintroduced into
      highly metastatic rat prostate cancer cells by using microcell-mediated
      chromosome transfer. Loss of heterozygosity (LOH) at polymorphic microsatellite
      loci on the human chromosome 11 was examined in human prostate cancer tissues.
      RESULTS: The minimum region of human chromosome 11 that contained the KAI1 gene
      was located on the proximal region of 11p11.2 divided by the D11S554 locus. The
      percentage of LOH or allelic imbalance at the D11S1344 locus, which is located on
      the same region as the KAI1 locus, in metastasis tissues from autopsy cases who
      died from metastatic prostate cancer was 70% (7 of 10 informative cases), whereas
      the percentages in primary tumors from the same cases and from cases with
      clinically localized prostate cancer were 33% (3 of 9 informative cases) and 8%
      (1 of 12 informative cases), respectively. CONCLUSIONS: These findings
      demonstrate a high frequency of LOH or allelic imbalance at the centromeric
      region of 11p, which contains the KAI1 gene in advanced prostate cancer.

PMID- 9254901
TI  - Serum levels of endothelial and neural cell adhesion molecules in prostate
      cancer.
AB  - BACKGROUND: Tumorigenesis and progression to metastatic disease are accompanied
      by changes in the expression of cell adhesion molecules (CAMs). Normally
      expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1,
      NCAM, and E-selectin, are altered and overexpressed in progressive disease and
      metastases. Abnormal levels of these latter CAMs have been observed in melanoma
      and carcinomas of the colon and breast, and NCAM is overexpressed in small-cell
      lung carcinoma (SCLC). The objective of this study was to determine if serum
      levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients with
      benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and
      identify prostate cancers with high potential for progression to metastatic
      disease. METHODS: Serum levels of these CAMs were determined by ELISA in serum
      from normal males and females and from patients with BPH and CaP before and after
      treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma,
      and small-cell lung carcinoma were also evaluated, as soluble CAMs have been
      reported to be elevated in these cancer patients. RESULTS: ICAM-1 levels were
      elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (P
      = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma
      (P = 0.0001). NCAM levels were elevated in the sera of patients with SCLC (P =
      0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and
      pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients
      were significantly greater than in BPH (P = 0.0005) and CaP patients with
      pathologically determined organ-confined (P = 0.0014) or nonorgan-confined
      disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH
      patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels for
      normal age-matched donors. None of the CAMs were found to offer an advantage over
      prostatic-specific antigen (PSA) for monitoring CaP patients following definitive
      radiotherapy, radical prostatectomy, or hormonal therapy. CONCLUSIONS: The
      results of this study indicate that serum ICAM-1, VCAM-1, NCAM, and E-selectin
      are not clinically useful biomarkers for differentiating CaP from BPH, for
      predicting progression, for identifying metastatic potential, or for monitoring
      treatment.

PMID- 9254902
TI  - Changes in patterns of prostate cancer care in the United States: results of
      American College of Surgeons Commission on Cancer studies, 1974-1993.
AB  - BACKGROUND: Advances in medical and public health practice have led to many
      changes in patterns of prostate cancer care. Data from several studies of
      prostate cancer by the Commission on Cancer of the American College of Surgeons
      provide information on the directions, magnitudes, and consequences of these
      changes. METHODS: The Commission on Cancer conducts patient care evaluation (PCE)
      studies based on the voluntary participation of hospital cancer programs and
      their tumor registries. PCE studies have been conducted repeatedly for prostate
      cancer covering patients diagnosed as early as 1974 and as recently as 1990. In
      addition, the National Cancer Data Base of the Commission on Cancer collects data
      for all forms of cancer from throughout the country. The Commission on Cancer,
      the American Cancer Society, and the American Urologic Association also has
      conducted a focused survey of radical prostatectomy outcomes. In aggregate, these
      multiple studies have accrued 179,366 reports on treatment of prostate cancer
      patients. RESULTS: Predominant among practice changes are new techniques of
      prostate cancer detection and initial evaluation which have led to shifts in
      disease stage at the time of initial therapy. The proportion of prostate cancer
      that is localized at the time of detection has increased. Use of radiation
      therapy and radical prostatectomy has increased as the selection of hormone
      treatment and no cancer-directed treatment have decreased. Five-year prostate
      cancer survival has improved for every stage of disease. CONCLUSIONS: The
      multiple studies by the Commission on Cancer provide data that are not available
      from other sources. Continued monitoring of prostate cancer patterns of care may
      be useful in measuring progress in control of this common disease.

PMID- 9254903
TI  - Detection of the isoenzymes of wheat grain proteinase A.
AB  - A new method for the purification of wheat cysteine proteinase A which plays a
      key role in the mobilization of seed storage proteins during germination has been
      developed. It consists of (NH4)2SO4 fractionation, gel filtration, and both ion
      exchange and hydrophobic chromatography. Constancy of the specific activity of
      chromatographic fractions and their SDS-electrophoretic pattern indicates the
      homogeneity of the final enzyme preparation. However, electrophoresis in
      nondenaturing conditions revealed three protein bands of similar intensity, each
      showing proteolytic activity. The N-terminal sequences of all three
      electrophoretic components are identical. They are also identical to a segment of
      the amino acid sequence deduced from one of several cDNA clones derived from
      closely related, but non-identical mRNAs that accumulate in the aleurone layer of
      gibberellic acid-treated wheat. It is very likely that the three electrophoretic
      components found are isoenzymes encoded by cDNA clones described by these
      authors.

PMID- 9254904
TI  - Developmental regulation of the Drosophila Tropomyosin I (TmI) gene is controlled
      by a muscle activator enhancer region that contains multiple cis-elements and
      binding sites for multiple proteins.
AB  - Developmental gene regulation in vertebrate somatic muscles involves the
      cooperative interaction of MEF2 (myocyte-specific enhancer-binding factor 2) and
      members of the b-HLH (basic helix-loop-helix) family of myogenic factors. Until
      recently, however, nothing was know about the factors that control the
      developmental regulation of muscle genes during embryogenesis in Drosophila. The
      Drosophila Tropomyosin I (TmI) gene contains a proximal and distal muscle
      enhancer within the first intron that regulates its expression in
      embryonic/larval and adult muscles. We have recently shown that the 355-bp
      proximal enhancer contains a binding site for the Drosophila homologue of
      vertebrate MEF2 and that MEF2 acts cooperatively with a basal level muscle
      activator region to direct high level muscle expression in transgenic flies. The
      92-bp muscle activator region, however, does not contain any consensus E-box
      (CANNTG) binding site sequences for b-HLH myogenic factors, suggesting the MEF2
      may interact with other factors to regulate muscle genes in Drosophila. In this
      study we have used mutation analysis and germ-line transformation to analyze cis
      acting elements within the muscle activator region that regulate its expression
      in transgenic flies. We have identified a 71-bp region that is sufficient for low
      basal level temporal- and muscle-specific expression in the embryo, larva, and
      adult. Substitution mutations within the muscle activator region have identified
      several cis-element regions spanning 60-bp that are required for either full or
      partial muscle activator function. An analysis of proteins that bind to this
      region by gel mobility shift assay and copper nuclease footprinting has allowed
      us to identify the sites in this region at which multiple proteins complex and
      interact. We propose that these cis-elements and the proteins that they bind
      regulate muscle activator function and together with MEF2 are capable of
      regulating high level muscle expression.

PMID- 9254905
TI  - Precocious sporulation and developmental lethality in yelA null mutants of
      Dictyostelium.
AB  - A novel developmental gene, yelA, has been found that plays as essential role in
      regulating terminal differentiation of Dictyostelium discoideum. Strains in which
      yelA is disrupted by plasmid insertion are arrested at the tight mound stage but
      accumulate the bright yellow pigment characteristic of mature sori. Although
      these mutant strains do not form fruiting bodies, many of the cells encapsulate
      within the mounds. Sporulation occurs about 6 hours earlier in yelA- cells than
      in wild-type cells, accompanied by precocious expression of a prespore gene,
      spiA. However, the spores are defective and lose viability over a period of
      several hours. Unencapsulated cells also die unless they are dissociated from the
      mounds and shaken in suspension. The yelA gene was isolated by plasmid rescue and
      found to encode a protein of 102 kDa in which the N-terminal sequence shows
      significant similarity to domains found in the eIF-4G subunits of the
      translational initiation complex eIF-4F. In wild-type cells yelA mRNA first
      accumulates at 8 hours of development and is maintained in both prespore and
      prestalk cells until culmination when it is found only is stalk cells. Mutations
      in yelA can partially suppress the block to sporulation in mutant strains in
      which either of the prestalk genes tagB or tagC is disrupted such that an
      encapsulation signal is not produced. It appears that premature encapsulation is
      normally inhibited by YelA until a signal is received from prestalk cells during
      culmination.

PMID- 9254906
TI  - Genomic organization of the mouse fertilin beta gene that encodes an ADAM family
      protein active in sperm-egg fusion.
AB  - The fertilin alpha and beta genes (Ftna and Ftnb, respectively) encode a sperm
      surface heterodimer that functions in sperm-egg fusion. They are the first
      identified members of a large gene family coding for multidomain membrane
      proteins (ADAMs) that include A Disintegrin And Metalloprotease domain. In this
      study, we report the isolation and structural organization of the mouse fertilin
      beta gene. The gene is present as a single copy and covers a region of
      approximately 55 kilobases in the genome. The fertilin beta gene is composed of
      at least 20 exons interrupted by 19 introns. The sizes of the exons are
      relatively small and vary from 56 to 193 bases; the sizes of introns vary from
      350 bases to 9.4 kilobases. The exon-intron boundaries conform to the GT/AG rule
      with one exception: GC replaces GT at the 5' splice site in intron 13. Comparison
      of genomic organization between mouse fertilin beta and the previously sequenced
      ADAM family gene, human MDC [Katagiri et al. (1995): Cytogenet Cell Genet 68:39
      44] showed 12 conserved exon-intron boundaries. In addition, we analyzed the
      fertilin alpha gene, demonstrating that more than one gene is present in the
      mouse genome.

PMID- 9254907
TI  - Temporal and spatial regulation of a putative transcriptional repressor
      implicates it as playing a role in thyroid hormone-dependent organ
      transformation.
AB  - Thyroid hormone (T3) induces both larval cell death and adult cell proliferation
      and differentiation during amphibian metamorphosis. We have previously isolated a
      bZip transcription factor (TH/bZip) as a T3 response gene in the metamorphosing
      Xenopus intestine. We demonstrate that the Xenopus TH/bZip gene is a direct T3
      response gene and ubiquitously regulated by T3 in tadpoles. Developmental in situ
      hybridization analyses have shown that TH/bZip gene is regulated in a cell-type
      specific manner that correlates with tissue transformation. In particular, it is
      found to be expressed in the larval intestinal epithelial cells prior to their
      apoptotic degeneration and in the proliferating adult cell types. However, the
      gene is repressed again upon adult cell differentiation. This regulation pattern
      mimics that of the thyroid hormone receptor (TR)beta genes. Since the TH/bZip
      gene is a direct T3-response gene, such a correlation suggests that TR beta may
      be involved in the regulation of the TH/bZip gene. More importantly, in situ
      hybridization reveals a strong spatiotemporal correlation of TH/bZip expression
      with the tissue-specific remodeling in the intestine, suggesting that TH/bZip
      gene may participate, depending on the cell types, in both inducing apoptosis and
      stimulating cell proliferation. A similar role has been reported for the proto
      oncogene c-myc, another leucine-zipper-containing transcription factor, in tissue
      culture cell systems.

PMID- 9254908
TI  - Green fluorescent protein/beta-galactosidase double reporters for visualizing
      Drosophila gene expression patterns.
AB  - We characterized 120 novel yeast Ga14-targeted enhancer trap lines in Drosophila
      using upstream activating sequence (UAS) reporter plasmids incorporating newly
      constructed fusions of Aequorea victoria green fluorescent protein (GFP) and
      Escherichia coli beta-galactosidase genes. Direct comparisons of GFP
      epifluorescence and beta-galactosidase staining revealed that both proteins
      function comparably to their unconjugated counterparts within a wide variety of
      Drosophila tissues. Generally, both reporters accumulated in similar patterns
      within individual lines, but in some tissues, e.g., brain, GFP staining was more
      reliable than that of beta-galactosidase, whereas in other tissues, most notably
      tests and ovaries, the converse was true. In cases of weak enhancers, we
      occasionally could detect beta-galactosidase staining in the absence of
      discernible GFP fluorescence. This shortcoming of GFP can, in most cases, be
      alleviated by using the more efficient S65T GFP derivative. The GFP/beta-gal
      reporter fusion protein facilitated monitoring several aspects of protein
      accumulation. In particular, the ability to visualize GFP fluorescence enhances
      recognition of global static and dynamic patterns in live animals, whereas beta
      galactosidase histochemistry affords sensitive high resolution protein
      localization. We present a catalog of Ga 14-expressing strains that will be
      useful for investigating several aspects of Drosophila melanogaster cell and
      developmental biology.

PMID- 9254909
TI  - Two two-gene macronuclear chromosomes of the hypotrichous ciliates Oxytricha
      fallax and O. trifallax generated by alternative processing of the 81 locus.
AB  - We describe the first know macronuclear chromosomes that carry more than one gene
      in hypotrichous ciliated protozoa. These 4.9- and 2.8-kbp chromosomes each
      consist almost exclusively of two protein-coding genes, which are conserved and
      transcribed. The two chromosomes share a common region that consists of a gene
      that is a member of the family of mitochondrial solute carrier genes (CR-MSC;
      [Williams and Herrick (1991): Nucleic Acids Res 19:4717-4724]. Each chromosome
      also carries another gene appended to its common region: The 4.9-kbp chromosome
      also carries a gene that encodes a protein that is rich in glutamine and charged
      amino acids and bears regions of heptad repeats characteristic of coiled-coils.
      Its function is unknown. The second gene of the 2.8 kbp chromosome is a
      mitochondrial solute carrier gene (LA-MSC); thus, the 2.8-kbp chromosomes
      consists of two mitochondrial solute carrier paralogs. Phylogenetic analysis
      indicates that the two genes were duplicated before ciliates diverged from the
      main eukaryotic lineage and were subsequently juxtaposed. The CR- and LA-MSC
      genes are each interrupted by three introns. The introns are not in homologous
      positions, suggesting that they may have originated from multiple group II intron
      transpositions. These chromosomes and their genes are encoded in the Oxytricha
      germline by the 81 locus. This locus is alternatively processed to generate a
      nested set of three macronuclear chromosomes, the 4.9- and 2.8-kbp chromosomes
      and a third (1.6 kbp) which consists almost exclusively of the shared common
      gene, CR-MSC. Such alternative processing is common in macronuclear development
      of O. fallax [Cartinhour and Herrick (1984): Mol Cell Biol 4:931-938]. Possible
      functions for alternative processing are considered; e.g., it may serve to
      physically link genes to allow co-regulation or co-replication by a common cis
      acting sequence.

PMID- 9254910
TI  - Mathematics as a basis for chemistry.
AB  - Mathematicians are increasingly publishing papers in which mathematics is applied
      to chemical problems. Examination of some of these papers reveals that while they
      contain genuine contributions to chemistry they tend to avoid the more
      interesting and difficult problems. The "forward" problem of estimation of
      physical properties from a compound's structure, for example, has seen many
      publications, a proportion of which have been successful. The "reverse" problem,
      prediction of the structures which possess given properties, is only rarely
      examined and never by mathematicians. This is unfortunate because these problems
      are mathematically complex and mathematicians could make significant
      contributions by bringing their skills to bear on such questions.

PMID- 9254911
TI  - Constructing protein models for ligand-receptor binding thermodynamic
      simulations: an application to a set of peptidometic renin inhibitors.
AB  - Structure-based design is the application of ligand-receptor modeling to predict
      the activity of a series of molecules that bind to a common receptor for which
      the molecular geometry is available. Successful structure-based design requires
      an accurate receptor model which can be economically employed in the design
      calculations. One goal of the work reported here has been to reduce the size of a
      model structure of a macromolecular receptor to allow multiple ligand-receptor
      molecular dynamic (MD) simulations to be computationally economical yet still
      provide meaningful binding thermodynamic data. A scaled-down 10 A receptor model
      of the enzyme renin, when subjected to an alternate atomic mass constraint,
      maintains the structural integrity of the composite parent crystal structure. A
      second goal of the work has been to develop schemes to explore and characterize
      the protonation states of receptors and ligand-receptor systems. Application of
      the charge state characterization schemes to the hydroxyethylene and statine
      transition state inhibitors of renin in the training set suggests a
      monoprotonation state of the two active-site aspartate residues, where the lone
      proton resides on the outer carboxylate oxygen of Asp226 is most likely. For the
      reduced amide transition state inhibitors an active site consisting of both
      aspartates in the totally ionized state, and the ligand carrying a net +1.0
      charge, is most stable and consistent with experimental data.

PMID- 9254912
TI  - Prediction of ligand-receptor binding thermodynamics by free energy force field
      (FEFF) 3D-QSAR analysis: application to a set of peptidometic renin inhibitors.
AB  - A methodology is presented and applied in which the accurate estimation of ligand
      receptor binding thermodynamics is achieved by formulating the calculation as a
      QSAR problem. When the receptor geometry is known, the free energy force field
      (FEFF) ligand-receptor binding energy terms can be calculated and used as
      independent variables in constructing FEFF 3D-QSARs. The FEFF 3D-QSAR analysis of
      a series of transition state inhibitors of renin was carried out. From a
      statistical analysis of the free energy contributions to the binding process,
      FEFF 3D-QSARs were constructed that reveal the change in solvation free energy
      upon binding and the intramolecular vacuum internal energy of the ligand in the
      unbound state are the most significant FEFF terms in determining the binding free
      energy, delta G. Other terms, such as ligand stretching, bending, and torsion
      energy changes, the intermolecular van der Waals interaction energy, and change
      in ligand conformational entropy upon binding, are also found to make significant
      contributions in some FEFF 3D-QSAR delta G models and in delta H and delta S
      binding models. Overall, a relatively small number of the thermodynamic
      contributions to the ligand-receptor binding process dominates the thermodynamics
      of binding in a given model.

PMID- 9254913
TI  - Molecular design using the minireceptor concept.
AB  - Explicit molecular binding pockets were constructed and optimized around sets of
      superimposed ligands using the minireceptor concept. The resulting binding sites
      incorporate the properties of the different ligands and were shown to be suitable
      for the design of molecules presenting novel interaction patterns. Two
      applications of minireceptor construction and/or optimization, followed by
      molecular design are described. In the pursuit of new ligands mimicking the
      action of paclitaxel, a minireceptor was constructed using the primary amino acid
      sequence of the target protein as a guide. The active site extracted from a
      homology-based model of the serotonin 5-HT1A receptor was optimized around a set
      of three ligands using the same approach.

PMID- 9254914
TI  - Trends in capillary electrophoresis: 1997.
AB  - This article is intended to present an overview of developments in the field of
      capillary electrophoresis (CE) and its application to the analysis of micro
      environments. Instrumental developments in injection and detection methods and
      the separation chemistries are outlined. Emphasis is placed on methods and means
      that have significantly improved the capability of CE. Subsequently, several
      selected applications to the exploration of microenvironments such as CE-based
      sensors, CE on microchip, and single cell analysis are described. The recent
      advancements in these areas are highlighted.

PMID- 9254915
TI  - Nonneutral evolution of tandem repeats in the mitochondrial DNA control region of
      lagomorphs.
AB  - The mitochondrial DNA of the European rabbit (Oryctolagus cuniculus) contains a
      tandem array of 153-bp repeats in the vicinity of the replication origin of the H
      stand. Variation among molecules in the number of these repeats results in inter-
      and intraindividual length polymorphism (heteroplasmy). Generally, in an
      individual, one predominant molecular type is observed, the others representing a
      low percentage of the mtDNA content. At the tissue level, we observe a particular
      distribution of this polymorphism in the gonads compared with liver, kidneys, or
      brain, implying a relationship between the differentiation status of the cells
      and the types of new mtDNA molecules which appear and accumulate during lifetime.
      Similar tandem repeats were also found in the mtDNA noncoding region of European
      hares (Lepus europaeus), a cottontail (Sylvilagus floridanus), and a pika
      (Ochotona rufescens). The lengths and the sequences of these units evolve rapidly
      and in a concerted way, but the number of repeats is maintained in a narrow
      range, and an internal 20-bp segment is highly conserved. Constraints restrict
      the evolution of the primary sequence of these repeated units, the number of
      which is probably controlled by a stabilizing selection.

PMID- 9254916
TI  - A molecular phylogeny for aplocheiloid fishes (Atherinomorpha,
      Cyprinodontiformes): the role of vicariance and the origins of annualism.
AB  - Annual aplocheiloid killifish embryos possess a rare ability among vertebrates to
      enter stages of developmental arrest (diapause) when subjected to adverse
      environmental conditions. Previous morphological analyses have presented
      disparate hypotheses regarding the evolution of the intriguing life history
      associated with this phenomenon. We present a novel hypothesis of aplocheiloid
      relationships based on 1,009 bp of sequence data from three mitochondrial genes
      (cytochrome b, 12S rRNA, and 16S rRNA). Phylogenetic analysis using maximum
      parsimony, neighbor-joining, and maximum likelihood produce strongly congruent
      topologies. Our data confirm the monophyly of the Neotropical family Rivulidae,
      while demonstrating a paraphyletic Old World assemblage. The basal sister group
      position of Indo-Malaysian and Madagascaran taxa relative to a monophyletic South
      American/African dichotomy strongly indicates the role of vicariance in the
      diversification of these fishes in spite of their definition as secondary
      freshwater fish. The distribution of annualism onto this topology implies a
      single early origin for this suite of characters, prior to the divergence of
      South American and African taxa. If so, then annualism has since been lost
      several times during the evolution of genera now residing in permanent aquatic
      habitats. Paleoclimatic knowledge complements this scenario based on molecular
      characters.

PMID- 9254917
TI  - The origin and evolution of Ebola and Marburg viruses.
AB  - Molecular evolutionary analyses for Ebola and Marburg viruses were conducted with
      the aim of elucidating evolutionary features of these viruses. In particular, the
      rate of nonsynonymous substitutions for the glycoprotein gene of Ebola virus was
      estimated to be, on the average, 3.6 x 10(-5) per site per year. Marburg virus
      was also suggested to be evolving at a similar rate. Those rates were a hundred
      times slower than those of retroviruses and human influenza A virus, but were of
      the same order of magnitude as that of the hepatitis B virus. When these rates
      were applied to the degree of sequence divergence, the divergence time between
      Ebola and Marburg viruses was estimated to be more than several thousand years
      ago. Moreover, most of the nucleotide substitutions were transitions and
      synonymous for Marburg virus. This suggests that purifying selection has operated
      on Marburg virus during evolution.

PMID- 9254918
TI  - The main features of the craniate mitochondrial DNA between the ND1 and the COI
      genes were established in the common ancestor with the lancelet.
AB  - We have cloned the mitochondrial DNA fragment extending from tRNA-Leu to the
      cytochrome oxidase subunit 1 (COI) genes of Branchiostoma lanceolatum, Myxine
      glutinosa, Lampetra fluviatilis, and Scyliorhinus caniculus and have determined
      their respective gene sequences and organization. In all four species, this
      region contains the ND1 and ND2 genes and the genes coding eight tRNAs, namely,
      tRNA-Ile, -Gln, -Met, -Trp, -Ala, -Asn, -Cys, and -Tyr. The gene order is the
      same in the hagfish, lamprey and dogfish. In the lancelet, the location of the
      tRNA genes is slightly different. The mitochondrial code of Myxine, Lampetra, and
      Scyliorhinus is identical to that of vertebrates. The code used by the lancelet
      is the same with the exception of AGA (a stop codon in vertebrates), which codes
      for glycine in the lancelet. From the comparison of the four maps with already
      published ones for other species, we propose that the main features of the
      craniate mtDNA between the ND1 and COI genes were established in the common
      ancestor to cephalochordates and vertebrates more than 400 MYA. The origin of
      replication of the light-strand (Ori-L), usually located between the tRNA-Asn and
      tRNA-Cys genes in vertebrates, was not found in the lancelet, hagfish, or lamprey
      (Lampetra). In contrast, it was found in the dogfish. Thus the position of Ori-L
      was established for the first time in the common ancestor to the Chondrichthyes
      and Osteichthyes and remained present in all later-emerging vertebrates.

PMID- 9254919
TI  - Nucleotide sequence divergence in the A+T-rich region of mitochondrial DNA in
      Drosophila simulans and Drosophila mauritiana.
AB  - We have determined the nucleotide sequences of two regions within the A+T-rich
      region of mitochondrial DNA (mtDNA) in the siIII type of Drosophila simulans and
      the maI type of D. mauritiana. The sequences of the two regions in siIII and maI
      are almost identical. The sequences include elements corresponding to the type I
      and type II repeats elements and the T-stretches as reported in D. melanogaster;
      an approximately 340-bp region (A region) adjacent to the tRNA(Ile) gene includes
      a part of the type II repeat element, and an approximately 440-bp region (B
      region) includes a central portion of the A+T-rich region between the type I and
      type II repeat arrays. Each sequence of the two species was compared with those
      of D. melanogaster and D. yakuba. The sequences of the A region are relatively
      well conserved among the four species. The alignment of the two sequences of the
      B region with those of D. melanogaster and D. yakuba requires numerous
      insertions/deletions. For both regions, nucleotide differences between D.
      simulans or D. mauritiana and D. melanogaster are similar to those between the
      two and D. yakuba. The tendency is obvious in a subregion within the type II
      repeat element in the A region. These findings suggest that the rate of
      nucleotide substitution in the subregion is accelerated in the lineage leading to
      D. melanogaster. Loss of functional constraint in the stem-loop-forming sequence
      is proposed for this acceleration.

PMID- 9254920
TI  - Evolution of isochores in rodents.
AB  - The most deviant isochore pattern within mammals was found in rat and mouse; most
      other mammals possess a different kind of isochore organization called the
      "general pattern." However, isochore patterns remain largely unknown in rodents
      other than mouse and rat. To investigate the taxonomic distribution of isochore
      patterns in rodents, we sequenced the nuclear gene LCAT (lecithin:cholesterol
      acyltransferase) from 17 rodents species (bringing the total of LCAT sequences in
      rodent to 19) and compared their GC contents at third codon positions and in
      introns. We also analyzed an extensive sequence database from rodents other than
      rat and mouse. All murid LCAT sequences are much poorer in GC than all nonrodent
      LCAT sequences, and the hamster sequence database shows exactly the same isochore
      pattern as rat and mouse. Thus, all murids share the same special isochore
      pattern--GC homogenization. LCAT sequences are GC-poor in hystricomorphs too, but
      the guinea pig sequence database indicates that large changes in GC content occur
      without an overall modification of the isochore pattern. This novel mode of
      isochore evolution is called GC reordering. LCAT sequences also show that the
      evolution of isochores in sciurids and glirids is nonconservative in comparison
      with that in nonrodents. Thus, at least two novel patterns of isochore evolution
      were found. No rodent investigated to date shared the general mammalian pattern.

PMID- 9254921
TI  - Evolution of functional diversification of the paired box (Pax) DNA-binding
      domains.
AB  - The Pax gene family consists of tissue-specific transcriptional regulators that
      always contain a highly conserved DNA-binding domain with six alpha-helices
      (paired domain), and, in many cases, a complete or residual homeodomain. Numerous
      genes of this family have been identified in animals, with the largest number
      found in vertebrates. Our evolutionary analyses indicate that the vertebrate Pax
      gene family consists of four well-defined and statistically supported groups:
      group I (Pax-1, 9), II (Pax-2, 5, 8), III (Pax-3, 7), and IV (Pax-4, 6). Group I
      paired domains share a most recent common ancestor with Drosophila Pox meso,
      group II with Pox neuro, group III with paired and gooseberry, and group IV with
      the eyeless gene. Two groups containing complete homeodomains (III and IV) are
      distantly related, and the intergroup relationships are (I,III), (II,IV). These
      four major groups arose before the divergence of Drosophila and vertebrates prior
      to the Cambrian radiation of triploblastic metazoan body plans. We conducted an
      analysis of fixed radical amino acid differences between groups in a phylogenetic
      context. We found that all four fixed radical amino acid differences between
      groups I and III are located exclusively in the N-terminal alpha-helices.
      Similarly, groups II and IV show three fixed radical differences in these alpha
      helices but at positions different from those in groups I and III. Implications
      of such fixed amino acid differences in potentially generating sequence
      recognition specificities are discussed in the context of some recent
      experimental findings.

PMID- 9254922
TI  - Phylogenetic reconstruction of vertebrate Hox cluster duplications.
AB  - In vertebrates and the cephalochordate, amphioxus, the closest vertebrate
      relative, Hox genes are linked in a single cluster. Accompanying the emergence of
      higher vertebrates, the Hox gene cluster duplicated in either a single step or
      multiple steps, resulting in the four-cluster state present in teleosts and
      tetrapods. Mammalian Hox clusters (designated A, B, C, and D) extend over 100 kb
      and are located on four different chromosomes. Reconstructing the history of the
      duplications and its relation to vertebrate evolution has been problematic due to
      the lack of alignable sequence information. In this study, the problem was
      approached by conducting a statistical analysis of sequences from the fibrillar
      type collagens (I, II, III, and IV), genes closely linked to each Hox cluster
      which likely share the same duplication history as the Hox genes. We find
      statistical support for the hypothesis that the cluster duplication occurred as
      multiple distinct events and that the four-cluster situation arose by a three
      step sequential process.

PMID- 9254923
TI  - Microsatellite evolution--a reciprocal study of repeat lengths at homologous loci
      in cattle and sheep.
AB  - The application of microsatellites in evolutionary studies requires an
      understanding of the patterns governing their evolution in different species. The
      finding that homologous microsatellite loci are longer, i.e., containing more
      repeat units, in human and in other primates has been taken as evidence for
      directional microsatellite evolution and for a difference in the rate of
      evolution between species. However, it has been argued that this finding is an
      inevitable consequence of biased selection of longer-than-average microsatellites
      in human, because cloning procedures are adopted to generate polymorphic and,
      hence, long markers. As a test of this hypothesis, we conducted a reciprocal
      comparison of the lengths of microsatellite loci in cattle and sheep using
      markers derived from the bovine genome as well as the ovine genome. In both
      cases, amplification products were longer in the focal species, and loci were
      also more polymorphic in the species from which they were originally cloned. The
      crossing pattern that we found suggests that interspecific length differences
      detected at homologous microsatellite loci are the result of biased selection of
      loci associated with cloning procedures. Hence, comparisons of microsatellite
      evolution between species are flawed unless they are based on reciprocal analyses
      or on genuinely random selection of loci with respect to repeat length.

PMID- 9254924
TI  - The age of the common ancestor of eukaryotes and prokaryotes: statistical
      inferences.
AB  - In this paper, a simple distance measure was used to estimate the age (T) of the
      common ancestor of eukaryotes and prokaryotes which takes the rate variation
      among sites and the pattern of amino acid substitutions into account. Our new
      estimate of T based on Doolittle et al.'s data is about 2.5 billion years ago
      (Ga), with 95% confidence interval from 2.1 to 2.9 Ga. This result indicates (1)
      that Doolittle et al.'s estimate (approximately 2.0 Ga) seems too recent, and (2)
      that the traditional view about the divergence time between eukaryotes and
      prokaryotes (T0 = 3.5 Ga) can be rejected at the 0.1% significance level.

PMID- 9254925
TI  - Mitochondrial gene arrangement of the horseshoe crab Limulus polyphemus L.:
      conservation of major features among arthropod classes.
AB  - Numerous complete mitochondrial DNA sequences have been determined for species
      within two arthropod groups, insects and crustaceans, but there are none for a
      third, the chelicerates. Most mitochondrial gene arrangements reported for
      crustaceans and insect species are identical or nearly identical to that of
      Drosophila yakuba. Sequences across 36 of the gene boundaries in the
      mitochondrial DNA (mtDNA) of a representative chelicerate. Limulus polyphemus L.,
      also reveal an arrangement like that of Drosophila yakuba. Only the position of
      the tRNA(LEU)(UUR) gene differs; in Limulus it is between the genes for
      tRNA(LEU)(CUN) and ND1. This positioning is also found in onychophorans,
      mollusks, and annelids, but not in insects and crustaceans, and indicates that
      tRNA(LEU)(CUN)-tRNA(LEU)(UUR)-ND1 was the ancestral gene arrangement for these
      groups, as suggested earlier. There are no differences in the relative
      arrangements of protein-coding and ribosomal RNA genes between Limulus and
      Drosophila, and none have been observed within arthropods. The high degree of
      similarity of mitochondrial gene arrangements within arthropods is striking,
      since some taxa last shared a common ancestor before the Cambrian, and contrasts
      with the extensive mtDNA rearrangements occasionally observed within some other
      metazoan phyla (e.g., mollusks and nematodes).

PMID- 9254926
TI  - Confidence intervals of evolutionary distances between sequences and comparison
      with usual approaches including the bootstrap method.
AB  - Two methods are commonly employed for evaluating the extent of the uncertainty of
      evolutionary distances between sequences: either some estimator of the variance
      of the distance estimator, or the bootstrap method. However, both approaches can
      be misleading, particularly when the evolutionary distance is small. We propose
      using another statistical method which does not have the same defect: interval
      estimation. We show how confidence intervals may be constructed for the Jukes and
      Cantor (1969) and Kimura two-parameter (1980) estimators. We compare the exact
      confidence intervals thus obtained with the approximate intervals derived by the
      two previous methods, using artificial and biological data. The results show that
      the usual methods clearly underestimate the variability when the substitution
      rate is low and when sequences are short. Moreover, our analysis suggests that
      similar results may be expected for other evolutionary distance estimators.

PMID- 9254927
TI  - Phylogenetic relationships of bolitoglossine salamanders: a demonstration of the
      effects of combining morphological and molecular data sets.
AB  - We analyzed sequence data for 555 bp of the mitochondrial gene cytochrome b in
      plethodontid salamanders, taken from 18 ingroup (tribe Bolitoglossini) and 4
      outgroup (tribe Plethodontini) taxa. There were 257 variable sites, of which 219
      were phylogenetically informative. Sequence differences among taxa exceeded 20%,
      and there were up to 15% amino acid differences among the sequences. We also
      analyzed 37 morphological (including karyological) characters, taken from the
      literature. Data were analyzed separately and then combined using parsimony and
      likelihood approaches. There is little conflict between the morphological and DNA
      data, and that which occurs is at nodes that are weakly supported by one or both
      of the data sets. Treated separately, the morphological and DNA data provide
      strong support for some nodes but not for others. The combined data act
      synergistically so that good support is obtained for nearly all of the nodes in
      the tree. Recent divergences are supported by silent transitions, and older
      divergences are supported by a combination of morphological, karyological, DNA
      transversion, and amino acid changes. Eliminating silent changes from the DNA
      data improves the consistency index and improves some bootstrap and decay index
      values for several deeper branches in the tree. However, the combined data set
      with all characters included provides a better supported tree overall. Maximum
      likelihood and parsimony with all of the data give not only the same topology but
      also remarkably similar branch lengths. Results of this analysis support the
      monopoly of the supergenera Hydromantes and Batrachoseps, and of a sister group
      relationship of Batrachoseps and the supergenus Bolitoglossa (represented in this
      study one species of the genus Bolitoglossa).

PMID- 9254928
TI  - Identification of a novel TAP2 allele in a Colombian black population: gene
      conversion, ancestral intermediate or convergent change?

PMID- 9254929
TI  - Relaxation in a high-stress environment: the molecular bases of extensible cell
      walls and cell enlargement.

PMID- 9254930
TI  - Plant intercellular communication via plasmodesmata.

PMID- 9254931
TI  - Leaf morphogenesis in flowering plants.

PMID- 9254932
TI  - Building a root: the control of patterning and morphogenesis during root
      development.

PMID- 9254933
TI  - Epidermal cell fate and patterning in leaves.

PMID- 9254934
TI  - Last exit: senescence, abscission, and meristem arrest in Arabidopsis.

PMID- 9254937
TI  - Acute appendicitis in children in a community hospital: a five year review.
AB  - OBJECTIVE: To review appendectomy cases in children at a small community hospital
      and to compare with experience at larger centers. DESIGN: A five-year
      retrospective study. SETTING: Bartlett Regional Hospital, Juneau, Alaska.
      PATIENTS AND METHODS: Records of children age 14 and younger who underwent
      appendectomy from 1991 through 1996 were reviewed; 79 charts were found. Cases
      were grouped as simple appendicitis, advanced appendicitis, and appendectomy
      without appendicitis. Variables considered included: length of symptoms at first
      contact, time from onset until surgery, presence or absence of classical
      symptoms, post-operative complications, length of hospital stay. RESULTS AND
      CONCLUSION: 51 cases (64.6%) of simple appendicitis, 22 cases (27.9%) of advanced
      disease, and 6 cases (7.6%) of normal appendix occurred. Advanced disease was
      high (66.7%) in children less than 5, and low (22.7%) in ages 10-14. Parental
      delay > 48 hours in seeking care was a significant factor in advanced disease,
      professional delay (time from first exam until surgery) was not. Post-surgical
      complications occurred in 7 (31.8%) cases of advanced disease and in none of the
      cases with simple appendicitis. Advanced disease cases had an average hospital
      stay of 8.59 days (+/-2.92) vs. 3.86 days (+/-1.46) for simple appendicitis.
      Review of appendicitis in children at this hospital compared favorably with the
      experience at larger medical centers.

PMID- 9254935
TI  - Oligosaccharins, brassinolides, and jasmonates: nontraditional regulators of
      plant growth, development, and gene expression.
AB  - Each of the nontraditional plant hormones reviewed in this article,
      oligosaccharins, brassinolides, and JA, can exert major effects on plant growth
      and development. However, in many cases, the mechanisms by which these compounds
      are involved in the endogenous regulation of morphogenesis remain to be
      established. Nevertheless, the use of mutant or transgenic plants with altered
      levels or perception of these hormones is leading to phenomenal increases in our
      understanding of the roles they play in the life cycle of plants. It is likely
      that in the future, novel modulators of plant growth and development will be
      identified; some will perhaps be related to the peptide encoded by ENOD40 (Van de
      Sande et al., 1996), which modifies the action of auxin.

PMID- 9254938
TI  - Expanding use of thrombolytic therapy in the treatment of acute myocardial
      infarction in rural Alaskan hospitals.
AB  - This paper focuses on clinical quality improvement comparing the results of two
      studies done approximately one year apart on treatment of acute myocardial
      infarction in four rural hospitals. The purpose of both studies was to determine
      how often eligible, elderly Medicare patients with acute myocardial infarction
      received thrombolytic treatment and aspirin. The studies were done by abstracting
      medical records for the calendar year 1993 and again in the year between October
      1, 1994 and September 30, 1995. The results show that the use of thrombolytic
      therapy in these hospitals for the Medicare population increased by 40% between
      1993 and 1995, a statistically significant increase (95% confidence intervals
      (CI) 20.1% to 60.0%). The rate of thrombolytic therapy among eligible Medicare
      patients went from 25.5% in 1993 to 65.7% in 1995. The use of aspirin also
      increased by 12.5% which was borderline significant (95% CI, 0.0% to 34%). The
      results were not as dramatic because the baseline for aspirin use with acute
      myocardial infarction was already 67.5% in 1993. These results indicate that the
      treatment of acute myocardial infarction is evolving closely in line with the
      American Heart Association/American College of Cardiology 1996 guidelines.
      Studies of clinical quality improvement such as this are now requirements for
      hospital certification.

PMID- 9254936
TI  - Light modulation of vegetative development.

PMID- 9254939
TI  - Notes/reflections based on personal experience.

PMID- 9254941
TI  - Sense and specificity in computer based patient records in general practice. The
      ICPC-ICD-10 conversion structure as the Holy Grail.

PMID- 9254940
TI  - Pipe-smoking along the Yukon (1867).

PMID- 9254942
TI  - Coordinated care. Are we putting the cart before the horse?

PMID- 9254943
TI  - General practitioners' perceptions regarding coordinated care.
AB  - OBJECTIVE: To explore the attitudes of general practitioners to the changing
      roles in the coordination of complex patient care. METHOD: A questionnaire survey
      was distributed with Australian Doctor. RESULTS: GPs were found to fall into four
      broad groups in relation to care coordination: those who do not want to expand
      their role in coordination of care (30%); those who would like to expand their
      role in coordination of care, but do not want to take costs into account when
      making decisions about patient care (34%); those who would like to expand their
      role in coordination of care, do think costs should be taken into account, but do
      not wish to be involved in budget management (21%); and those who would like to
      expand their role in coordination of care and be involved in budget management
      (22%). CONCLUSION: In the context of the introduction of managed care in
      Australia, this survey highlights the potential for GPs to take on a range of
      roles and responsibilities under these arrangements.

PMID- 9254944
TI  - Managing people with HIV/AIDS--the involvement of Victorian general
      practitioners.
AB  - OBJECTIVE: To examine aspects of knowledge, attitudes, behaviour and practice
      (KABP) of Victorian general practitioners (GPs) in relation to human
      immunodeficiency virus (HIV), as part of a larger KABP study relating to GPs and
      sexually transmissible diseases (STDs). METHOD: Questionnaire survey of 520
      randomly selected GPs. RESULTS: A response rate of 85% was obtained. Most
      respondents were aware of the major risk factors for HIV infection and most GPs
      obtained consent before HIV testing. More than 22% of respondents had ordered an
      HIV test that was positive and 39% had been involved with the management of HIV
      positive patients (asymptomatic, symptomatic or both). The gender of the
      practitioner (male), greater frequency of STD diagnosis and greater level of ease
      in treating homosexual men were all significantly associated with having ordered
      an HIV test that was positive and with ongoing management of asymptomatic and
      symptomatic HIV positive patients, whereas practitioner age, frequency of
      advising on safe sex and providing contraceptive advice were not. CONCLUSION:
      Thirty-nine per cent of Victorian GPs are now managing HIV positive patients,
      representing a 17% increase since 1989. We found that GP knowledge of HIV
      transmission and infection control was generally good although information on
      knowledge and practice beyond initial diagnosis was not sought. Given the
      evidence of a significant association between practitioner experience in HIV/AIDS
      management and survival of their patients, there is a need for further research
      into the educational and support needs of Australian GPs in relation to this
      increasingly complex area of clinical practice.

PMID- 9254945
TI  - A survey on the diagnosis and management of asthma in young children.
AB  - OBJECTIVE: To examine how asthma in children less than 5 years of age is
      diagnosed and managed by general practitioners (GPs) and how this compares with
      the National Asthma Campaign guidelines. METHOD: A cross sectional postal survey
      of 164 GPs in the eastern suburbs of Melbourne in November, 1995. RESULTS:
      General practitioners diagnose asthma primarily on history, with the symptoms of
      nocturnal cough, wheeze and chronic cough considered as most important. Wheeze is
      the most important sign. An overuse of oral beta 2 agonists and inhaled
      corticosteroids were found. CONCLUSIONS: Asthma is diagnosed primarily on history
      and the presence of a wheeze helps to confirm the diagnosis. Management is
      appropriate overall, but there seems to be an overtreatment of mild asthmatics,
      and an overuse of inhaled corticosteroids.

PMID- 9254946
TI  - A model for the evaluation of computerised codes. The Gabrieli Medical
      Nomenclature as an example.
AB  - The objective of this article was to evaluate the Gabrieli Medical Nomenclature
      (GMN) as a coding system for primary care, using a system of five criteria. These
      were: the infrastructure supporting the coding system; the code structure; ease
      of use of the codes; the reproducibility of coding; the usefulness of the codes
      to Australian GPs. The performance of the GMN was evaluated as being at, or below
      the level of other coding systems in each of the assessment areas. It was found
      that the GMN has no advantages over other, existing coding systems. Evaluation of
      coding systems should include an assessment of the reproducibility of coding and
      its usefulness to Australian general practice.

PMID- 9254947
TI  - A new coding tool for computerised clinical systems in primary care--ICPC plus.
AB  - Standardised classifications are essential for reliable information management.
      The International Classification of Primary Care (ICPC) provides a recognised
      structure for classifying problems managed in general practice but lacks
      sufficient details for medical records. This paper describes an extended version
      of ICPC, based on the natural language of GPs in Australia, for use in
      computerised clinical systems.

PMID- 9254948
TI  - Integration of undergraduate and postgraduate general practice education--does it
      work?
AB  - Academic general practice remains a small part of most medical schools. One
      topical method of creating larger units is to integrate the undergraduate and
      postgraduate education roles. This paper describes the structure of the General
      Practice and Rural Health Unit at the North Queensland Clinical School, where
      education, clinical service and policy development roles are combined to create
      one of Australia's larger academic general practice centres. Issues which have
      facilitated and challenged the development are discussed in this reflective paper
      describing the first 3 years of operation.

PMID- 9254949
TI  - Attitudes of rural general practitioners towards undergraduate medical student
      attachments.
AB  - OBJECTIVE: Increasing exposure of undergraduate medical students to rural
      practice is a key component of the national effort in Australia to redress the
      rural workforce shortage. For this exposure to be successful, willing cooperation
      of current rural general practitioners is essential. To date there has been no
      formal assessment of rural general practitioners' attitudes to having
      undergraduate medical students attached to their practice. METHOD: A descriptive
      survey, using a mailed questionnaire was sent to all 316 general practitioners
      currently practising in rural areas of South Australia, as identified from the
      database maintained by the South Australian Rural Practice Training Unit.
      RESULTS: A 71.5% response rate (n = 225) was achieved, of which 203 were eligible
      for inclusion. Of these, 176 doctors had medical student attachments in their
      practice on at least one occasion; 74.4% of whom (n = 131) perceived the
      attachments to have a positive experience on their continuing medical education
      experience, and 81.1% (n = 142) described a positive experience on their
      professional development. However, 52.6% (n = 92) felt the attachments had a
      negative effect on their income. Almost all the doctors who were included in the
      survey (94.6%, n = 192) were willing to have students attached to their practice
      in the future for between one to two weeks. Of these, 169 wanted quality
      assurance points, 112 wanted financial reimbursement, and 108 wanted 'academic
      status' with a university. CONCLUSION: The results suggest that rural general
      practitioners are willing to have students attached to their practice for periods
      between one to two weeks, providing they receive quality assurance points, and to
      a lesser extent, financial reimbursement and academic status.

PMID- 9254950
TI  - Clinical audit--linking continuing medical education (CME) and practice
      assessment (PA).
AB  - The Quality Assurance (QA) Program of the Royal Australian College Of General
      Practitioners has required doctors to engage in practice assessment (PA)
      activities. Clinical audit is one of these activities and has been used as an
      assessment tool in the Graduate Diploma in Family Medicine at Monash University,
      in impact evaluation of educational programs as well as a means of pooling
      morbidity data for research purposes and peer review. Examples of these uses of
      clinical audit are cited, with discussion in greater detail in relation to a
      dermatology course, cardiovascular risk factor detection and ongoing management
      of congestive cardiac failure. Doctors participating in these audit activities
      have almost invariably described them as a valuable reflective educational
      exercise with changes in clinical practice occurring after the audit in a number
      of instances.

PMID- 9254951
TI  - General practitioner participation in 'Morning Report' at a major teaching
      hospital.
AB  - General practitioners attending 'Morning Report' have provided information on the
      general practice management of a wide range of conditions and have promoted the
      benefits of improved communication between general practitioners and hospital
      doctors. By collecting data on a range of problems at the community hospital
      interface, they are in a position to identify and act upon issues with important
      implications for health care. This activity is recommended to all general
      practitioners working in association with a major hospital.

PMID- 9254952
TI  - QE-Mail--improving communication between the hospital and general practitioners.
AB  - OBJECTIVE: To describe the process of developing a therapeutic bulletin with a
      view to improving communications between providers of primary and secondary care
      and to survey general practitioners to assess their responses to the bulletin and
      to ascertain their further information needs. METHODS: A clinical panel was
      convened to select relevant topics for inclusion in the bulletins. The topic for
      each bulletin was researched and written using standard information sources and
      relevant experts. A survey was mailed with the first edition of the bulletin, to
      GPs in the Western Division of General Practice and in country areas, and to
      Directors of Nursing from country hospitals. RESULTS: The overall response rate
      to the survey was 41%. The majority of respondents had read the bulletin and
      found it useful. Most thought that the presentation, in terms of length, detail
      and layout, was suitable. Topics suggested for future editions included
      antibiotics, antihypertensives and antidepressants. CONCLUSION: The bulletin, QE
      Mail, was well received and helped to inform GPs about current practices at the
      hospital. Future directions include the use of e-mail to distribute the bulletins
      and a follow up survey to determine if the bulletin is still meeting
      practitioners' needs.

PMID- 9254954
TI  - Do patients with asthma fill their prescriptions?

PMID- 9254953
TI  - A pre-discharge project--does GP willingness equal involvement?
AB  - OBJECTIVE: To compare GPs' willingness to participate in a GP pre-discharge
      project as measured by a survey, with actual participation rates. To identify the
      characteristics of GPs likely to make a pre-discharge visit to frail, aged
      inpatients admitted under the care of a geriatrician. METHOD PRE-IMPLEMENTATION
      GP SURVEY: Survey of a random sample of 100 GPs from the Central Sydney area
      using a standardised questionnaire. PRE-DISCHARGE VISIT PROJECT: Information on
      actual participation rates and GPs who declined to make a pre-discharge visit was
      obtained from an audit of Division of General Practice records. Information on
      Patient characteristics was obtained from patient interviews and medical records.
      The survey was conducted at the Balmain Hospital and Concord Repatriation and
      General Hospitals located within the Central Sydney Area Health Service. The
      subjects were GPs practising in central Sydney and patients admitted under the
      care of a geriatrician at Balmain and Concord Hospitals. RESULTS: Twenty-nine per
      cent of GPs reported that they were willing to undertake visits without
      remuneration and 71% reported they were willing to make a pre-discharge visit if
      remunerated. Fifty-three per cent of GPs actually complied with a request to make
      a remunerated pre-discharge visit. This was 18% less than the rate determined by
      the survey. GPs were less likely to make a visit if they were solo practitioners
      and not members of the Division. Patients who were more dependent, as measured by
      total Barthel's score, and those from nursing homes were less likely to receive a
      visit. CONCLUSION: GP surveys may overestimate participation rates in Division
      projects. In reality, it appears difficult for GPs to accommodate pre-discharge
      visits in a general practice routine and the offered remunerations may not be
      adequate compensation for time lost when undertaking a pre-discharge visit.
      Lastly, some GPs may not see a benefit in visiting more dependent patients.

PMID- 9254955
TI  - Interview with Brian Mouatt. Interview by Mike Grace.

PMID- 9254956
TI  - Uses of the self-retaining photographic retractor.

PMID- 9254957
TI  - The future of dental amalgam: a review of the literature. Part 7: Possible
      alternative materials to amalgam for the restoration of posterior teeth.
AB  - This is the last in a series of articles on the future of dental amalgam. It
      considers possible alternative materials to amalgam for the restoration of
      posterior teeth. The materials discussed are gold inlays, gold foil, gallium
      alloys, and tooth coloured non-metal alternatives including glass-ionomer
      cements, composite resins, glass-ionomer-resin hybrids, compomers and ceramics.
      The clinical indications for these restorations are first described along with
      their potential clinical problems and their mean survival rates in comparison
      with dental amalgam. Secondly, the safety of composite resins is considered and
      potential toxic and hypersensitive effects of these materials are discussed.
      Finally, it is concluded that the present evidence does not appear to demonstrate
      that dental amalgam is hazardous to the health of the general population. It
      does, however, recommend that in continuing to use amalgam dentists must use
      strict mercury hygiene procedures to avoid risk to their staff and contamination
      of the environment. It seems that mercury contamination of the environment is
      likely to be the main reason for any future government action against the
      continued clinical use of dental amalgam.

PMID- 9254958
TI  - Burnout and stress-related factors among junior staff of three dental hospital
      specialties.
AB  - OBJECTIVE: To determine whether occupational stress, health status, job
      satisfaction and burnout differed between the three major hospital dental
      specialties, and to compare this data with previous studies. DESIGN: A cross
      sectional survey. SETTING: The regional dental teaching hospital and outlying
      hospital units in Merseyside in 1993. SUBJECTS AND METHODS: All 52 junior
      hospital dentists in the Merseyside area were invited to complete a self-report
      questionnaire to be returned by post. Up to three reminders were sent. 42 staff
      replied (81% response rate). MAIN OUTCOME MEASURES: Occupational Stress
      Indicator, Maslach Burnout Inventory. RESULTS: The profile of stressors was
      comparable to a previously reported sample of hospital dentists. Job satisfaction
      varied significantly across specialties (P < 0.015) whereas personal achievement
      was reported to be strong regardless of the nature of work. Self-reported health
      (physical and mental) was similar across specialties. 10% of respondents were
      suffering burnout. Depersonalisation (a result of extended and demanding contacts
      with patients) was significantly (P < 0.05) greater in restorative and oral
      surgery specialties in comparison with orthodontists. CONCLUSIONS: Although short
      term stressors among hospital dental staff were not different between
      occupational groups, some important longer term effects were identified.

PMID- 9254959
TI  - Clinical guidelines for dentistry: will they be useful?
AB  - OBJECTIVE: To review the literature on the development and effectiveness of
      clinical guidelines. DESIGN: Literature review of relevant publications following
      a Medline search. Publications that reported studies investigating effectiveness
      of guidelines were confined to randomised controlled trials. CONCLUSIONS: If
      guidelines are to be effective they should be (i) based on high levels of
      scientific evidence, (ii) developed with input from the dentists who will be
      using them and (iii) presented in a satisfactory manner. Importantly, the
      effectiveness of the guidelines should be rigorously evaluated.

PMID- 9254960
TI  - Acute idiopathic thrombocytopaenic purpura in childhood: report of a case
      presenting in general dental practice.
AB  - Acute idiopathic thrombocytopaenic purpura is the most common of the
      thrombocytopaenias of childhood. Clinically it is associated with petechiae,
      mucocutaneous bleeding and occasionally haemorrhage into tissues. The oral mucosa
      is frequently involved. This paper describes a case presenting in general dental
      practice.

PMID- 9254961
TI  - Eight weeks in Warsaw.
AB  - In October and November 1996 I worked for 8 weeks in the Department of Prosthetic
      Dentistry, Institute of Stomatology, Medical Academy of Warsaw, Poland, at the
      invitation of the Head of Department, Professor E Spiechowicz. My objective was
      to carry out an academic audit of the teaching of partial denture prosthetics.

PMID- 9254962
TI  - An outbreak of diarrhetic shellfish poisoning.

PMID- 9254963
TI  - Needlestick malaria with tragic consequences.

PMID- 9254964
TI  - [Some YAC contig construction and long range physical mapping at human X
      chromosome Xp11.3-21.3].
AB  - Human X chromosome short arm Xp11.3-p21.3 is an area, where several genetic
      disease gene loci are located. In this work, the YAC conting construction, long
      range physical mapping were done for this region. Some DNA probes and STS markers
      were used for YAC screening. Totally 77 YACs were obtained from the YAC libraries
      of CEPH, ICRF and ours. The size determination, 26 pairs of microsatelite STS
      analysis, single copy probe hybridization, Alu-PCR finger printing and long range
      physical mapping were conducted with these YACs. These results allowed us to map
      these YACs, and finally 6 YAC contigs were obtained in Xp11.3-21.3, covering
      about 15.3 Mb. This work will greatly facilitate the positional cloning of
      disease genes or the genome sequencing in this important region.

PMID- 9254965
TI  - [Genetic diversity and phylogenetic relationships among Chinese Macacas based on
      protein electrophoresis].
AB  - In this paper, using protein electrophoresis method, we studied
      proteinpolymorphism and genetic divergence of 5 species in Genus Macaca: M.
      mulatta, M. arctoides, M. assamensis, M. thibetana, M. fascicularis. A total of
      30 genetic loci were analyzed for 29 individuals, including 4 Nycticebus pygmaeus
      as outgroup. For the 19 M. mulatta, 9 loci were found to be polymorphic.
      Accordingly, the percentage of polymorphic loci, P = 0.3; the mean number of
      alleles, A = 1.4, and the mean heterozygosity, H = 0.1045, indicating a rather
      high level of genetic diversity in this species. Furthermore, 10 loci showed
      polymorphic among the 5 species, which can be used as information loci for
      phylogenetic reconstruction. Three programs (conml, neighbor, fitch) in PHYLIP
      3.5 c were chosen to construct phylogenetic trees. All of the three trees show
      support a close relationship between M. mulatta and M. fascicularis. However, two
      trees have the same topology, suggesting that M. arctoides belongs to an
      independent species group, while M. assamensis and M. thibetana are closely
      related and belong to another species group, and the other tree gives a different
      topology which implies that M. arctoides, M. assamensis and M. thibetana belong
      to one species group.

PMID- 9254966
TI  - [Mitochondrial DNA sequence evolution and conservation relevance of snub-nosed
      langurs].
AB  - The classification and phylogenetic relationships of the snub-nosed langurs
      (Rhinopithecus) are still open questions. We have sequenced a mitochondrial
      cytochrome b gene fragment from R. roxellana, R. bieti, R. avunculus and
      Presbytis phayrei. There are 47 sites (19%) characterized by variation. A series
      of evolutionary trees with concordant topology has been derived by using
      parsimony, maximum likelihood and distance methods, which may have resolved the
      evolutionary relationships of the three golden monkey species. R. bieti is more
      closely related to R. avunculus than to R. roxellana. The divergence among those
      three species occurred about 2-6 million years ago. Our results suggest that
      Rhinopithecus is a valid genus, and avunculus should be placed into this genus.
      Our non-invasive genetic analysis provided useful information for the genetic
      management of the captive population at the Kunming Institute of Zoology.

PMID- 9254976
TI  - [Study on transposition behavior of IS5376 in Bacillus stearothermophilus].
AB  - IS5376 and IS5377 are two transposable elements discovered in Bacillus
      stearothermophilus. Analysis of random samples revealed that the frequency of
      transposition of IS5376 from CU21 chromosome to plasmids pFDC5 and pFDC12 was
      much higher at 65 degrees C than that at 48 degrees C while that of IS5377 was
      very low at both 48 degrees C and 65 degrees C. The exact nature of the
      temperature effect is obscure at present from evidences obtained so far it is
      concluded that this is a consequence of the innate property of IS5376.
      Furthermore, it was found that a certain degree of site specificity in
      transposition was evident and that a direct repeat of 4 or 5 bp of the target DNA
      appeared at the site of transposition.

PMID- 9254977
TI  - [Constuction of an improved system for the determination of fidelity of
      polymerase in PCR].
AB  - A system used for the determination of fidelity of DNA polymerase in PCR was
      developed in E.coli and was used to determine the fidelity of FD DNA polymerase
      in PCR amplication. Frame shift and base substitution mutations were created in
      vitro in the lacZ gene in pUC118 and pUC119. As a result, a set of six derived
      plasmids namely pFDFM118 and pFDFM119 (-1 frame shift), pFDFP118 and pFDFP119 (+1
      frame shift), pFDFU118 and pFDFU119 (base substitution) were obtained. All of
      them failed to carry out lacZ alpha-complementation in E.coli MV1184 and the
      colonies appeared white on medium with X-Gal and IPTG consequently. PCR reaction
      was carried out using these derived plasmids as templates and the PCR products
      were ligated to specially constructed cloning vectors pFDFL118 or pFDFL119, and
      the ligated products were used to transform MV1184. If any back mutation happens
      to occur during PCR, the transformants would appear blue on medium with X-Gal and
      IPTG. By scoring the number of blue and white colonies, the fidelity of DNA
      polymerase can be calculated. With this system the error of replication of the FD
      DNA polymerase was found to be 10(-5)-10(-6).

PMID- 9254978
TI  - Estimation of event-related synchronization changes by a new TVAR method.
AB  - The modeling of nonstationary electroencephalogram (EEG) with time-varying
      autoregressive (TVAR) models is discussed. The classical least squares TVAR
      approach is modified so that prior assumptions about the signal can be taken into
      account in an optimal way. The method is then applied to the estimation of event
      related synchronization changes in the EEG. The results show that the new
      approach enables effective estimation of the parameter evolution of the time
      varying EEG with better time resolution compared to previous methods. The new
      method also allows single-trial analysis of the event-related synchronization.

PMID- 9254979
TI  - Spectral analysis of a thalamus-to-cortex seizure pathway.
AB  - Physiological evidence has shown that the anterior thalamus (AN) and its
      associated efferents/afferents constitute an important propagation pathway for
      one animal model of generalized tonic-clonic epileptic seizures. In this study we
      extend and confirm the support for AN's role by examining neuroelectric signal
      indicators during seizure episodes. We show that the electroencephalogram (EEG)
      recorded from AN is highly coherent with the EEG derived from the cortex (CTX).
      By removing the effects of another thalamic nucleus, posterior thalamus (PT)
      unaffiliated with the tract linking AN to cortex-partial coherence analysis
      leaves the CTX/AN coherence undiminished. The most robust band of strong CTX-AN
      coherence is centered around the spike-wave pacing frequency of 1-3 Hz. Partial
      multiple coherence analysis techniques are used to remove the possible signal
      contribution from hippocampus in addition to PT. The CTX-AN coherence still
      remains undiminished in the low-frequency bands. Conclusive evidence from
      coherence studies and other spectral measures reaffirm the special role of the AN
      in the propagation of seizure activity from subcortex to cortex.

PMID- 9254980
TI  - Multivariate analysis of muscular fatigue during bicycle ergometer exercise.
AB  - The purpose of this study is to estimate the endurance threshold in terms of
      muscular fatigue during bicycle ergometer exercise. The problems to be solved are
      induced by dynamic movement and the physiological variation of muscle activity:
      that is, the progression and impairment of muscle activity occur simultaneously.
      First of all, we used multichannel recordings of myoelectric (ME) signals to
      reduce the effect by the movement of a bipolar surface electrode relative to the
      innervation zones. Second, since even the different types of ME parameters
      contain redundant information on muscular fatigue, we used the principal
      component analysis (PCA) to represent the meaningful information by small
      dimensions. Moreover, we proposed a total evaluation pattern to discriminate
      muscular fatigue from progression of muscle force at a glance. The total
      evaluation pattern shows the proportion of first principal component, the
      components of the first eigenvector, and the correlation coefficients as a
      function of the work load. The assessment using the total evaluation pattern
      divided eight subjects into three groups, whereas these subjects were not
      identified by a specific ME parameter.

PMID- 9254981
TI  - A fuzzy clustering approach to EP estimation.
AB  - The problem of extracting a useful signal (a response) buried in relatively high
      amplitude noise has been investigated, under the conditions of low signal-to
      noise ratio. In particular, we present a method for detecting the "true" response
      of the brain resulting from repeated auditory stimulation, based on selective
      averaging of single-trial evoked potentials. Selective averaging is accomplished
      in two steps. First, an unsupervised fuzzy-clustering algorithm is employed to
      identify groups of trials with similar characteristics, using a performance index
      as an optimization criterion. Then, typical responses are obtained by ensemble
      averaging of all trials in the same group. Similarity among the resulting
      estimates is quantified through a synchronization measure, which accounts for the
      percentage of time that the estimates are in phase. The performance of the
      classifier is evaluated with synthetic signals of known characteristics, and its
      usefulness is demonstrated with real electrophysiological data obtained from
      normal volunteers.

PMID- 9254982
TI  - Analysis of abnormal signals within the QRS complex of the high-resolution
      electrocardiogram.
AB  - This paper presents a new, quantitative approach to measuring abnormal intra-QRS
      signals, using the high-resolution electrocardiogram (HRECG). These signals are
      conventionally known as QRS "notches and slurs." They are measured qualitatively
      and form the basis for the ECG identification of myocardial infarction. The HRECG
      is used for detection of ventricular late potentials (LP), which are linked with
      the presence of a reentry substrate for ventricular tachycardia (VT) after a
      myocardial infarction. LP's are defined as signals from areas of delayed
      conduction which outlast the normal QRS period. Our objective is to quantify very
      low-level abnormal signals that may not outlast the normal QRS period. In this
      work, abnormal intra-QRS potentials (AIQP) were characterized by removing the
      predictable, smooth part of the QRS from the original waveform. This was
      represented as the impulse response of an ARX parametric model, with model order
      selected empirically from a training data set. AIQP were estimated using the
      residual of the modeling procedure. Critical AIQP parameters to separate VT and
      non-VT subjects were obtained using discriminant functions. Results suggest that
      AIQP indexes are a new predictive index of the HRECG for VT. The concept of
      abnormal intra-QRS potentials permits the characterization of pathophysiological
      signals contained wholly within the normal QRS period, but related to
      arrhythmogenesis. The new method may have other applications, such as detection
      of myocardial ischemia and improved ECG identification of the site of myocardial
      infarction, particularly in the absence of Q waves.

PMID- 9254983
TI  - A model for the design and evaluation of algorithms for closed-loop
      cardiovascular therapy.
AB  - Developing a clinically useful closed-loop drug delivery system can be extremely
      time consuming and costly. One approach to reducing the time and cost associated
      with developing closed-loop systems is to reduce the number of animal experiments
      and perform an extensive set of simulation studies. Through simulations, a closed
      loop controller's performance can be evaluated over a complete spectrum of the
      patient population, including boundary conditions. Simulation studies are
      repeatable, offering significant advantages in comparing modifications in control
      algorithms. Finally, simulation studies can be performed in a fraction of the
      time required for animal studies, at a fraction of the cost. We have developed a
      simulator, that included a nonlinear pulsatile-flow cardiovascular model, a
      physiological regulatory mechanism, and the pharmacology of four frequently
      titrated cardiovascular drugs. This simulator has already been used in the design
      and evaluation of two closed-loop algorithms-a self-tuning regulator (STR) and a
      multiple model adaptive controller (MMAC)-for blood pressure control during and
      after cardiac surgery.

PMID- 9254984
TI  - The effects of inhomogeneities and anisotropies on electrocardiographic fields: a
      3-D finite-element study.
AB  - The aim of this study was to quantify the effects of selected inhomogeneities and
      anisotropies on computed electric potential fields associated with the
      electrocardiographic forward problem. The model construction was based on the
      Utah Torso model and included geometry for major anatomical structures such as
      subcutaneous fat, skeletal muscle, and lungs, as well as for epicardial fatpads,
      major arteries and veins, and the sternum, ribs, spine, and clavicles. Measured
      epicardial potentials served as the electrical source for solutions to the
      electrocardiographic forward problems computed using the finite element method
      (FEM). The geometry of the torso model for each simulation was constant, but
      different combinations of conductivities were assigned to individual organs or
      tissues. Comparisons of different conductivity combinations followed one of two
      basic schemes: 1) a homogeneous torso served as the reference against which we
      compared simulations with a single organ or tissue and assigned its nominal
      conductivity, or 2) a fully inhomogeneous torso served as the reference and we
      removed the effect of individual organs or tissues by assigning it the
      homogeneous conductivity value. When single inhomogeneities were added to an
      otherwise homogeneous isotropic model, anisotropic skeletal muscle (at a 15:1
      anisotropy ratio) and the right and left lung had larger average effects (12.8,
      12.7, and 12.1% relative error (RE), respectively) than the other inhomogeneities
      tested. Our results for removing single inhomogeneities show that the
      subcutaneous fat, the anisotropic skeletal muscle (with the degree of anisotropy
      equal to 7:1), and the lungs have larger average impacts on the body surface
      potential distributions than other elements of the model (with values of 14.9,
      12.6, and 11.7% RE, respectively). The results also show that the size of the
      effect depended strongly on the distribution of epicardial potentials. The
      results of this study suggest that accurate representation of tissue
      inhomogeneity has a significant effect on the accuracy of the forward solution,
      with regions near the torso surface playing a larger role, in general, than those
      near the heart.

PMID- 9254985
TI  - A robust reconstruction of sparse biomagnetic sources.
AB  - Inequalty constraints are introduced to a normalized minimum-L1-norm estimator,
      which gives a sparse solution of the biomagnetic inverse problem. The constraints
      have a numeric tolerance to take into account the measurement ambiguity caused by
      noise. Computer simulation and phantom-data analysis show how the solution is
      improved by the constraints with a moderate tolerance; the improvement is
      examined in noisy conditions such that signal-to-noise ratios (SNR's) are lower
      than 10 dB.

PMID- 9254986
TI  - Influence of tissue resistivities on neuromagnetic fields and electric potentials
      studied with a finite element model of the head.
AB  - Modeling in magnetoencephalography (MEG) and electroencephalography (EEG)
      requires knowledge of the in vivo tissue resistivities of the head. The aim of
      this paper is to examine the influence of tissue resistivity changes on the
      neuromagnetic field and the electric scalp potential. A high-resolution finite
      element method (FEM) model (452,162 elements, 2-mm resolution) of the human head
      with 13 different tissue types is employed for this purpose. Our main finding was
      that the magnetic fields are sensitive to changes in the tissue resistivity in
      the vicinity of the source. In comparison, the electric surface potentials are
      sensitive to changes in the tissue resistivity in the vicinity of the source and
      in the vicinity of the position of the electrodes. The magnitude (strength) of
      magnetic fields and electric surface potentials is strongly influenced by tissue
      resistivity changes, while the topography is not as strongly influenced.
      Therefore, an accurate modeling of magnetic field and electric potential strength
      requires accurate knowledge of tissue resistivities, while for source
      localization procedures this knowledge might not be a necessity.

PMID- 9254987
TI  - Computational aspects of finite element modeling in EEG source localization.
AB  - A comparison is made of two different implementations of the finite element
      method (FEM) for calculating the potential due to dipole sources in
      electroencephalography (EEG). In one formulation (the direct method) the total
      potential is the unknown that is solved for and the dipole source is directly
      incorporated into the model. In the second formulation (the subtraction method)
      the unknown is the difference between the total potential and the potential due
      to the same dipole in an infinite region of homogeneous conductivity,
      corresponding to the region where the dipole is located. Both methods have the
      same FEM system matrix. However, the subtraction method requires an additional
      calculation of flux integrations along the edges of the elements in the
      computation of the right-hand side (RHS) vector. It is shown that the subtraction
      method is usually more accurate in the forward modeling, provided the flux
      integrations are computed accurately. Errors in calculating the flux integrations
      may result in large errors in the forward solution due to the ill-conditioned
      nature of the FEM system matrix caused by the Neumann boundary condition. To
      minimize the errors, closed-form expressions for the flux integrations are used
      for both linear and quadratic triangular elements. It is also found that FEM
      forward modeling errors may cause false extrema in the least-square objective
      function obtained from the boundary potential, near boundaries between media of
      differing conductivity. Multiple initial guesses help eliminate the possibility
      of the solution getting trapped in these false extrema.

PMID- 9254988
TI  - Long-term unrestrained measurement of stride length and walking velocity
      utilizing a piezoelectric gyroscope.
AB  - Long-term monitoring of stride length and walking velocity is considered to
      provide useful information for making decisions on treatment of patients with
      gait disabilities. The purpose of this study was to develop a device with the
      following design criteria: lightweight, easy attachment, little hindrance to the
      natural gait pattern, sufficient memory to record for one day, and practicality
      in clinical use. The prototype consists of a piezoelectric gyroscope, which
      detects angular velocity of the thigh of one leg in the sagittal plane, and a
      microprocessor-based maximum/minimum detector/data logger of a cyclic analog
      signal associated with the gait cycle. The accuracy of the device was evaluated
      in 20 normal subjects, seven above-the-knee (A/K) amputees, and ten hemiplegic
      patients, and relative accuracy within +/-15% was obtained, except for two
      special cases.

PMID- 9254989
TI  - A multichannel neural probe for selective chemical delivery at the cellular
      level.
AB  - A bulk-micromachined multichannel silicon probe capable of selectively delivering
      chemicals at the cellular level as well as electrically recording from and
      stimulating neurons in vivo has been developed. The process buries multiple flow
      channels in the probe substrate, resulting in a hollow-core device. Microchannel
      formation requires only one mask in addition to those normally used for probe
      fabrication and is compatible with on-chip signal-processing circuitry. Flow in
      these microchannels has been studied theoretically and experimentally. For an
      effective channel diameter of 10 microns, a channel length of 4 mm, and water as
      the injected fluid, the flow velocity at 11 torr is about 1.3 mm/s, delivering
      100 pl in 1 s. Intermixing of chemicals with the tissue fluid due to natural
      diffusion through the outlet orifice becomes significant for dwell times in
      excess of about 30 min, and a shutter is proposed for chronic use. The probe has
      been used for acute monitoring of the neural responses to various chemical
      stimuli in guinea pig superior and inferior colliculus.

PMID- 9254990
TI  - A silicon probe with integrated microheaters for thermal marking and monitoring
      of neural tissue.
AB  - This paper describes a microheater structure and its integration on a silicon
      microprobe. The 30-micron-diameter microstructure can be used to heat local areas
      of tissue or to measure local tissue temperature with an accuracy of < 0.3 degree
      C. The polysilicon microheater is suspended on a dielectric membrane to reduce
      undesired heat conduction to the probe substrate. The heating efficiency is 4.4
      degrees C/mW in still water and 2.2 degrees C/mW in guinea pig cortex. Six
      milliwatts applied for 2 min in cortex produces a temperature of 50 degrees C,
      creating a well-defined 50-micron-wide lesion for determining probe position
      histologically. Fabrication of the heaters requires no additional masking or
      processing steps in addition to those normally used for recording or stimulating
      probes.

PMID- 9254991
TI  - Multireference adaptive noise canceling applied to the EEG.
AB  - The technique of multireference adaptive noise canceling (MRANC) is applied to
      enhance transient nonstationarities in the electroeancephalogram (EEG), with the
      adaptation implemented by means of a multilayer-perception artificial neural
      network (ANN). The method was applied to recorded EEG segments and the
      performance on documented nonstationarities recorded. The results show that the
      neural network (nonlinear) gives an improvement in performance (i.e., signal-to
      noise ratio (SNR) of the nonstationarities) compared to a linear implementation
      of MRANC. In both cases an improvement in the SNR was obtained. The advantage of
      the spatial filtering aspect of MRANC is highlighted when the performance of
      MRANC is compared to that of the inverse auto-regressive filtering of the EEG, a
      purely temporal filter.

PMID- 9254992
TI  - Comparison of oral and intravenous hydration and diuretic, choice for protecting
      cisplatin induced nephrotoxicity.
AB  - Efficacy of oral hydration was compared with that of traditional intravenous
      hydration along with comparison of furasemide with mannitol in 65 patients of
      solid tumours undergoing Cisplatin based anterior chemotherapy. Incidence of
      reversible uremia was found to be equivalent in the series. Our results suggest
      superiority of oral hydration and furosemide diuresis owing to cost efficiency
      and patient comfort.

PMID- 9254993
TI  - Non Hodgkins lymphoma of ethmoidal sinus with rhinoorbital myiasis.
AB  - A patient with primary non-hodgkins lymphoma of the paranasal sinuses presenting
      as rhinoorbital myiasis is reported. The myiasis causing species was identified
      as Chrysomia bezziana Villeneuve. This case demonstrates the extreme destruction
      caused by myiasis and the inadequacy of therapeutic options available in such
      patients.

PMID- 9254994
TI  - Epithelioid haemangioma (benign haemangioendothelioma of bone)--a case report.
AB  - A case of epithelioid Haemangioma of the femur is presented. The patient, a 29
      year old woman, was treated by curettage and bone grafting, following which two
      "recurrent" tumours appeared. These were successfully removed by repeat
      curettage.

PMID- 9254995
TI  - Olfactory neuroblastoma in a case of cured lepromatous leprosy--chance occurrence
      or....

PMID- 9254996
TI  - Massive oedema of the ovary--a tumour-like condition--report of two cases.

PMID- 9254997
TI  - Splenic lymphocytes with circulating villous lymphocytes--a case report.
AB  - A 25 years old male presented with hepatomegaly splenomegaly and fever. He was
      diagnosed as splenic lymphoma with circulating villous lymphocytes (SLVL) on
      morphology, cytochemistry and immunocytochemistry performed on peripheral blood
      and bone marrow smears. Case is being presented because of rarity and unusual
      presentation at young age.

PMID- 9254999
TI  - Rosai-Dorfman disease presenting as a meningioma.
AB  - This report documents an unusal case of extranodal sinus histiocytosis (Rosai
      Dorfman disease) which produced a solitary intracranial mass lesion that was
      diagnosed clinically and radiologically as a meningioma. Morphological features
      have been described and literature extensively reviewed.

PMID- 9254998
TI  - Cytology. A valuable tool in prognostication of carcinoma breast.
AB  - Sixty consecutive cases of carcinoma breast diagnosed on fine needle aspiration
      cytology (FNAC) between July 1993 to June 1994 were studied prospectively.
      Nuclear grading was done on all cytologic smears, histologic grading was possible
      in only 22 cases. A good correlation was seen between nuclear grading on cytology
      and histology. Silver staining for nucleolar organizer region, and
      immunocytochemical staining for Ki-67 and C-erbB-2 could be done with ease on
      cytologic smears, providing necessary additional information on which to base the
      theraputic decisions.

PMID- 9255000
TI  - Assessment of chlorpromazine as radiation sensitizer and protector.
AB  - In vitro studies of chlorpromazine (CPZ) a popular anti-psychotic drug has shown
      radiation sensitizing effects at higher celluar concentration and protective
      effect at a lower concentration. The present study was designed to evaluate both
      sensitizing and protective effects in the treatment of advanced cancer of the
      cervix treated with hypofractionated external radiation and intratumoural
      injection of chlopromazine. Twenty patients were treated with intratumoural CPZ
      and radiation, while, 23 patients received radiation alone. A 52.94% complete
      response was noted in CPZ arm while 39.1% complete response in the control. A
      trend towards improved response is seen in CPZ group. Similarly patients who
      received CPZ showed significantly low proctitis rates.

PMID- 9255001
TI  - Baby Friendly Hospital Initiative: the Kerala experience.

PMID- 9255002
TI  - Effect of timing of cord clamping on the iron status of infants at 3 months.
AB  - OBJECTIVE: To determine the effect of timing of cord clamping on iron stores of
      term infants at 3 months of age. DESIGN: Prospective randomized clinical trial.
      SETTING: Tertiary hospital. SUBJECTS: 107 term neonates born to mothers with
      uncomplicated pregnancies and with hemoglobin more than 10 g/dl. METHODS: The 107
      infants were randomized to either early (n = 48) or late (n = 59) clamping groups
      at the time of delivery. Outcome measures evaluated were serum ferritin and
      hemoglobin in the infant at 3 months age. RESULTS: The groups were comparable for
      maternal age, parity, weight, supplemental iron intake in pregnancy, infant's
      birth weight, gestation and sex. Maternal and cord ferritin and hemoglobin values
      at birth were comparable. The infant ferritin at 3 months were also similar.
      CONCLUSIONS: Iron stores at 3 months in term infants are not influenced by timing
      of cord clamping at birth.

PMID- 9255003
TI  - Renal dysfunction detected by beta-2 microglobulinuria in sick neonates.
AB  - OBJECTIVE: To assess renal involvement in sick neonates referred to Neonatal
      Intensive Care Unit (NICU) using standard renal parameters and urinary beta 2
      microglobulin (B2M) excretion. DESIGN: Descriptive study. SETTING: Level II NICU
      and Nephrology Division of Pediatric Tertiary hospital. SUBJECTS: Forty six term
      sick neonates transferred for neonatal care and forty healthy term neonates who
      served as normal controls for urinary B2M excretion. METHODS: Standard tests
      including estimation of BUN, serum creatinine, blood pH, serum bicarbonate, serum
      and urinary electrolytes, urine output, and urinalysis. Urinary B2M levels were
      estimated from urine collected on day 1 (D1) and day 3 (D3) in all and 18
      neonates were tested on day 7 (D7) by radio-immunoassay method. RESULTS:
      Statistically significant elevation of mean values of urinary B2M were noted when
      sick neonates were compared with normal controls irrespective of primary disease,
      indicating tubular dysfunction (41/46 = 90%), whilst only 7 of these (17%) had
      abnormalities indicating renal involvement when judged by standard tests. Very
      high levels of urinary B2M were noted with birth asphyxia (n = 9), sepsis (n = 8)
      and renal disease (n = 7). Transient elevation of urinary B2M was noted in
      meconium aspiration syndrome (n = 4). Ten surgical cases with non renal
      congenital malformations showed high urinary B2M and 12/18 tested on D7 had
      persistently high urinary B2M due to multiple factors. CONCLUSIONS: Elevated
      urinary B2M in 90% sick neonates with apparently normal renal parameters in
      majority (34/41) indicates subclinical proximal tubular dysfunction especially in
      neonates with asphyxia, sepsis and congenital malformations. Persistent elevation
      of urinary B2M appear to be a sensitive diagnostic indicator for defining a group
      of neonates with subtle renal tubular dysfunction, the clinical relevance of
      which on long term basis is a subject for future study.

PMID- 9255004
TI  - Aerobic capacity and cardiopulmonary response to exercise in healthy south Indian
      children.
AB  - OBJECTIVE: To examine the cardiorespiratory response to exercise in healthy South
      Indian school children. DESIGN: Prospective study. SETTING: Cardiopulmonary
      Medicine Unit, Tuberculosis Research Center, Madras. SUBJECTS: Data was obtained
      on 47 girls and 48 boys in the age group 7 to 14 years. INTERVENTION: The
      children performed a graded maximal exercise stress test on a computerized
      treadmill system. RESULTS: Maximum oxygen consumption (VO2max) increased
      significantly at 11 years of age in both sexes but while boys showed a
      progressive increase beyond 11 years, girls did not. When corrected for weight,
      only boys at 14 years had a significant increase in VO2max/kg. Boys had higher
      values of VO2max/kg than girls at all ages. Minute ventilation and oxygen pulse
      values also increased in both sexes at 11 to 12 years. The VO2max of South Indian
      children was lower than the predicted values available for North American
      children when prediction equations based on height were used. However, when
      regression equations based on weight were used, the predicted values for North
      American and South Indian boys were similar, though values for the Indian girls
      were still low. CONCLUSIONS: Nutritional and sociocultural factors may play a
      role in determining VO2max of children from different populations, rather than
      ethnic differences alone.

PMID- 9255005
TI  - Nimesulide.

PMID- 9255006
TI  - Hirschsprung's disease.

PMID- 9255007
TI  - Usefulness of oxygen saturation (SpO2) monitoring in sick preterm neonates.

PMID- 9255008
TI  - Growth hormone in birth asphyxia.

PMID- 9255010
TI  - Kawasaki disease.

PMID- 9255009
TI  - An explosive outbreak of poliomyelitis in an orphanage in Delhi: risk factors for
      the unusually high attack rates.

PMID- 9255011
TI  - Nosocomial Salmonella bareilly septicemia: a nursery outbreak.

PMID- 9255012
TI  - Hypertrophic cardiomyopathy in infancy.

PMID- 9255013
TI  - Zellweger's syndrome.

PMID- 9255014
TI  - Central pontine myelinolysis in a normonatremic child.

PMID- 9255015
TI  - Congenital microgastria.

PMID- 9255016
TI  - Multiple sclerosis and systemic lupus erythematosus in a 10-year-old girl.

PMID- 9255017
TI  - Parents opinion on pre-primary education.

PMID- 9255018
TI  - Acute intermittent porphyria.

PMID- 9255019
TI  - Pulmonary blastoma.

PMID- 9255020
TI  - Partial liquid ventilation in neonates.

PMID- 9255021
TI  - Withdrawal of antiepileptic drugs after one year?

PMID- 9255022
TI  - Leprosy elimination.

PMID- 9255023
TI  - Emerging foodborne diseases.

PMID- 9255025
TI  - Defense mechanism of breast-milk.

PMID- 9255024
TI  - Current antibiotic choice for enteric fever.

PMID- 9255026
TI  - Reproducibility of self-administered questionnaire in epidemiological surveys.
AB  - We evaluated the reproducibility of data on intake frequency of 33 food items,
      beverage intake frequency of 3 items, drinking and smoking habits, and past
      history of 10 diseases obtained from a self-administered questionnaire. The
      survey subjects consisted of 263 aged 39 to 79 years individuals in the general
      population. After about one year interval these subjects consecutively
      participated in two surveys and were unintentionally requested to answer to the
      same questionnaire. The means of percent exact agreements for 33 food items were
      48.4% in all, 42.7% in males and 49.4% in females. The means of their percent
      agreements within one category difference were 85.4% in all, 83.3% in males and
      85.8% in females. The reproducibility of beverage intake frequency was the
      highest in green tea, followed in order by black tea and coffee. The percent
      exact agreements were 85.4% in males and 81.8% in females for drinking habit,
      87.5% in males and 99.0% in females for smoking habit, and 93.7% in males and
      97.2% in females for past history. The reproducibility of the self-administered
      questionnaire was the highest in past history, followed in order by smoking
      habit, drinking habit and dietary habit. The values of reproducibility were
      higher in females than in males except for drinking habit. Although reduction of
      categories was needed to improve the reproducibility, the obtained values from
      the self-administered questionnaire were sufficiently high for epidemiological
      studies.

PMID- 9255027
TI  - Ischaemic heart disease deaths in a Japanese rural area evaluated by clinical
      records.
AB  - A community-based survey to examine the actual number of ischaemic heart disease
      (IHD) deaths was undertaken in the western area of Toyama, a rural area with a
      population of 209,000. IHD deaths (International Classification of Diseases
      [ICD], ninth revision, codes 410-414) and heart failure (HF) deaths (ICD code
      428) according to the death certificate aged 15 to 74 in 1987 to 1990 were
      reevaluated from medical records using the criteria of the multinational
      monitoring of trends and determinants in cardiovascular disease (MONICA). Of 97
      subjects with IHD and of 170 subjects with HF according to the death certificate,
      85 cases (87.6%) and 143 cases (84.1%) could be examined, respectively. Using the
      MONICA criteria, of 85 subjects with IHD, 18 (21.2%) were reevaluated as
      "definite acute myocardial infarction (AMI)" and 30 (35.3%) as "possible AMI". On
      the other hand, of 143 subjects with HF, 1 (0.7%) were reevaluated as "definite
      AMI" and 12 (8.4%) as "possible AMI". From these results, the number of deaths as
      reevaluated IHD was estimated 104.5 in the study period, and it was 7.7% increase
      at least compared with the number of deaths judged from the death certificate.

PMID- 9255028
TI  - Factors related to the desire to enter a nursing home among elderly Japanese.
AB  - A cross-sectional survey on 1462 residents aged 55 years and over was conducted
      in an urban Japanese community to describe the factors influencing the people's
      desire to be institutionalized in later life. Multiple logistic regression
      analyses were performed to identify the variables associated with the desire for
      a nursing home placement. Men unsatisfied with their family bonds were more
      likely to desire placement in a nursing home. Younger women living alone or
      dissatisfied with their health status demonstrated a greater desire to be
      institutionalized. Among the elderly aged 70 years old and over, those who were
      dissatisfied with their family bonds or disabled in going outdoors were more
      likely to desire to live in a welfare facility. Gender, housing and financial
      characteristics were not significant factors for the desire to be
      institutionalized. Numerous factors were similar with actual predictors of
      nursing home placement; however, the elderly advancing in age were more concerned
      to remain at home. The present findings suggest that, aside from physical and
      mental disability, the family-related issue is the most important factor
      prompting the desire for institutionalization.

PMID- 9255029
TI  - A novel approach to assessing family history in the prevention of coronary heart
      disease.
AB  - Family history serves as the most important risk factor in prevention of coronary
      heart disease from youth. Prevalent methods of assessing family history, however,
      have serious drawbacks: a sudden rise of risk when a family member develops the
      disease; insufficient control for age among family members. We propose a simple
      quantitative method overcoming such drawbacks. Data on family history were
      obtained by questionnaires sent to 2,393 male high school students and their
      cholesterol levels were measured. Family risk from each family member was
      calculated by (30/Risk age)4, where the risk age was age at onset expressed by
      decade; if absent, it was replaced by present age or age at death. A mean score
      in a family served as the family risk. A total of 1,584 students and 17,127
      family members were analyzed. The proposed method yielded a statistically
      significant association (Odds ratio = 1.60; 95% confidence interval: 1.15-2.25)
      between the family risk (above or below the median) and the student's atherogenic
      index (above or below the 90th percentile) calculated from cholesterols. This
      association was stronger than those by conventional methods. The proposed method
      may be useful in prevention activities and its efficiency needs to be confirmed
      in other studies.

PMID- 9255030
TI  - Differing influence on delays in the case-finding process for tuberculosis
      between general physicians and specialists in Mongolia.
AB  - The objective of this study is to compare the influence on delays in the
      tuberculosis case-finding process according to the types of medical facilities
      initially visited. The subjects include 107 patients 16 years and older who were
      diagnosed with bacteriologically confirmed pulmonary tuberculosis at nine
      tuberculosis specialized facilities in Ulaanbaatar, Mongolia from May 1995 to
      March 1996. Patients were interviewed about their demographic and socioeconomic
      factors and their medical records were reviewed for measuring delays. Fifty-five
      patients initially consulted general physicians and the remaining 52 patients
      initially visited other types of facilities including tuberculosis specialized
      facilities. Patients who initially consulted general physicians had shorter
      patient's delays and longer doctor's delays than those who had visited other
      facilities first. Since the reduction of patient's delay outweighs the extension
      of doctor's delay among patients who initially consulted general physicians,
      their total delay was shorter than that of patients who visited other facilities
      first. The beneficial influence of consulting general physicians first on the
      total delay was observed after adjusting for patient's age, sex, residence area,
      family income and family history of tuberculosis. This finding indicates that
      general physicians play an important role in improving the passive case-finding
      process in Mongolia.

PMID- 9255032
TI  - Cigarette smoking and nasopharyngeal cancer: an analysis of the relationship
      according to age at starting smoking and age at diagnosis.
AB  - To examine whether the association between smoking and nasopharyngeal cancer
      varies according to age at starting smoking and age at diagnosis of the disease,
      we compared 113 men with nasopharyngeal cancer diagnosed between 31 and 59 years
      old who lived within eight cancer registry areas to 1,910 controls selected by
      random-digit telephone dialing. Compared to smoking which began at the age of 22
      years or older, the risk estimates were 0.4 (95% confidence interval (CI) 0.2
      0.9) and 0.8 (95%CI 0.4-1.5) for smoking begun at the ages of 18-21 and 17 years
      or younger, when adjusted for pack-years smoked and other potential confounders
      (p for trend > 0.8). In contrast, the risk estimates adjusted for age at starting
      smoking and other variables were 1.3 (95%CI 0.7-2.6), 1.9(95%CI 0.9-4.0) and
      3.0(95%CI 1.4-6.2) for 15-29.9, 30-44.9 and 45 or over, relative to 15 or less
      pack-years smoked (p for trend < 0.005). The analyses were repeated for subgroups
      in terms of age at diagnosis. The relative risks of ever-smoking and the dose
      effect relation between pack-years and the risk of the disease were not
      significantly different between men whose cancer was diagnosed at the age 49 or
      younger and those whose tumor was diagnosed between the ages 50 and 59. This
      study suggests that the magnitude of the risk for nasopharyngeal cancer may not
      vary significantly with the age at which smoking begins, and age at which the
      disease is diagnosed.

PMID- 9255031
TI  - Smoking habits, local brand cigarettes and lung cancer risk in Okinawa, Japan.
AB  - To disclose the association between smoking habits and lung cancer in Okinawa,
      Japan, we analyzed the data from a case-control study conducted from 1988 to
      1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched
      population controls, provided the following major findings. (a) The odds ratios
      (ORs) for current smokers relative to nonsmokers were much greater for squamous
      cell carcinoma than for adenocarcinoma. The OR was 9.82 for squamous cell
      carcinoma and 2.18 for adenocarcinoma in males, 28.2 and 1.14, correspondingly,
      in females. (b) Males who quit smoking for 20 years or more demonstrated no
      elevated lung cancer risk. (c) Among male current smokers, the more the number of
      cigarettes smoked per day, the higher the lung cancer risk for both cell types,
      but particularly for squamous cell carcinoma. In contrast, deep smoke inhalation
      significantly increased the risk for adenocarcinoma in particular. (d) Okinawan
      brand cigarettes were more strongly associated with the risk, compared with other
      brand ones. This finding might partly explain the higher frequency of lung cancer
      in males with the relatively lower smoking rate in Okinawa.

PMID- 9255033
TI  - The behavior of endometrial hyperplasia: a prospective study. Endometrial
      Hyperplasia Study Group.
AB  - OBJECTIVE: To clarify the behavior of endometrial hyperplasia in a prospective
      study. METHOD: Fifty-one patients with endometrial hyperplasia were followed up
      for 6 months. Samples of endometrial tissues were taken by uterine endometrial
      biopsy every 4 weeks during the first 3 months and at the end of follow-up.
      RESULTS: In 69% (35/51) of the patients histological picture of the endometrium
      became normal during the observation period. The lesions persisted in 17% (6/35)
      of the patients with simple hyperplasia, in 25% (1/4) of those with complex
      hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80%
      (4/5) of the patients with complex atypical hyperplasia. In the remaining 3
      patients with simple hyperplasia, the lesions progressed to complex atypical
      hyperplasia by the end of follow-up, after showing a normal endometrium.
      CONCLUSION: Most cases of endometrial hyperplasia, except for complex atypical
      hyperplasia, disappeared spontaneously within a short period of time.

PMID- 9255034
TI  - Effects of transforming growth factor-beta on the production of parathyroid
      hormone-related peptide in a human ovarian cancer cell line in vitro.
AB  - OBJECTIVE: We examined the effects of transforming growth factor-beta 1 (TGF-beta
      1) on intracellular parathyroid hormone-related peptide (PTHrP) production in a
      human ovarian cancer cell line (HOC-21). METHODS: Various concentrations of TGF
      beta 1 were added to a culture medium, and the numbers of cells were counted. HOC
      21 cells were cultured with or without TGF-beta 1, and intracellular PTHrP was
      measured by a radioimmunoassay kit that recognized the carboxy-terminal protein
      while counting the number of cells. Furthermore, a 125I-TGF-beta 1 binding assay
      was carried out. Values were analyzed statistically using an analysis of variance
      followed by an unpaired t-test. RESULTS: Five ng/ml of TGF-beta 1 inhibited the
      cell growth on Day 1 after plating. The TGF-beta 1 significantly (p < 0.05)
      stimulated intracellular PTHrP production in a time-dependent manner, also by Day
      1. A 125I-TGF-beta 1 binding study revealed that HOC-21 cells expressed a high
      affinity for the TGF-beta 1 receptor. CONCLUSION: The suppression of human
      ovarian cancer cell proliferation by TGF-beta 1 might be involved in the
      production of PTHrP.

PMID- 9255035
TI  - Characterization of macrophages isolated from the maternal surface of human term
      placenta by a new method of urokinase treatment.
AB  - OBJECTIVES: This study was performed to establish a new method for isolating
      macrophages from the maternal surface of human term placenta by urokinase
      treatment and to characterize their immunological functions. METHODS: Macrophages
      were recovered from the maternal surface of 6 human term placentas by urokinase
      treatment, adherence to plastic, and density gradient centrifugation using
      Percoll. The cells retrieved were tested for their surface markers by
      immunofluorescent staining. Their antigen-presenting capacity was examined by use
      of a mixed lymphocytes culture (MLC) test. In 2 cases, human leucocyte antigen
      (HLA) typing was performed. RESULTS: An average of 4 x 10(6) macrophage-like
      cells were obtained per whole placenta. More than 90% of them were positive for
      CD14, HLA-DR, and DQ surface antigens. An MLC test revealed that they had antigen
      presenting capacity. Of the 6 cases, 2 showed positive MLC test results with
      maternal peripheral-blood mononuclear cells. In 1 of the 2 cases, macrophages
      with paternal HLA phenotypes were identified. CONCLUSION: The urokinase treatment
      is a new useful method for isolating macrophages from the maternal surface of
      human term placenta. Using this method, we obtained macrophages of paternal HLA
      phenotypes (fetal origin) that might have migrated to the maternal surface of
      human term placenta.

PMID- 9255036
TI  - Pregnancy in a patient of Glanzmann's thrombasthenia with antiplatelet
      antibodies.
AB  - Glanzmann's thrombasthenia is an autosomal recessive, inherited platelet function
      disorder. There is an absence of glycoprotein (GP) IIb/IIIa on the platelet
      membrane which causes reduced platelet aggregation with a defective platelet
      haemostatic plug formation. The management of bleeding episodes in these patients
      with platelet transfusions may result in alloimmunization and make the successive
      transfusions less effective. Pregnancy and delivery is rare in these patients and
      is associated with a high risk of severe haemorrhage. We describe a primigravida
      with Glanzmann's thrombasthenia and alloimmunization who developed secondary
      postpartum haemorrhage and was successfully treated with oral prednisolone.

PMID- 9255037
TI  - Ultrasonographic diagnosis of fetal cholelithiasis.
AB  - A case of opacity in the fetal gallbladder was diagnosed by ultrasound. The
      lesion resolved spontaneously in the postnatal period. Careful follow-up
      ultrasound examinations are necessary for fetal cholelithiasis in the pre- and
      postnatal periods, and conservative management is mandatory.

PMID- 9255038
TI  - Effect of maternal exercise on fetal umbilical artery waveforms: the comparison
      of IUGR and AFD fetuses.
AB  - OBJECTIVE: To determine the effect of maternal exercise on the fetal blood flow
      of normal and growth-retarded fetuses. METHODS: The effect of maternal exercise
      on fetal blood flow was investigated with 24 pregnant women between 36 and 42
      weeks' gestation. Seventeen pregnancies were uncomplicated (normal group) and the
      other 7 were complicated with growth-retarded fetuses (IUGR group). They
      underwent graded walking on a treadmill with an upper limit of 150 bpm for the
      maternal heart rate. The systolic over diastolic velocity ratio (S/D ratio) of
      the umbilical artery was measured before exercise, and at 3, 5, 10, and 15
      minutes after exercise. RESULTS: The mean S/D ratio of the IUGR group before
      exercise was significantly higher than that of the normal group (p < 0.05). The
      S/D ratio did not change significantly after exercise, in either the normal group
      or the IUGR group. CONCLUSION: This study suggests that maternal exercise at this
      level of intensity and duration does not have any harmful effect, even on growth
      retarded fetuses that might have placental dysfunctions.

PMID- 9255039
TI  - Granulocytic sarcoma of uterine cervix as presentation of acute myeloid leukemia:
      a case report and review of literature.
AB  - Localized extramedullary collection of leukemic cells is termed as granulocytic
      sarcoma. Incidences of 2-8% in acute myeloid leukemia have been reported in
      various autopsy studies. In female it usually involves ovary. Since most of such
      tumors are asymptomatic, they are detected only at autopsy. We report here a case
      who manifested as abnormal vaginal bleeding, large cervical mass, renal failure,
      and aspergillous fungaemia. The patient died before she could be treated. From
      the present report it would appear that granulocytic sarcoma at times may precede
      other manifestations of leukemia.

PMID- 9255040
TI  - Outcome of abruptio placentae in normotensive and hypertensive patients in Aga
      Khan University Hospital, Pakistan.
AB  - The aim of our study was to compare the perinatal and maternal outcome in
      hypertensive women experiencing abruptio placentae with that of normotensive
      women. We hypothesized that hypertensive women experiencing abruptio had a less
      favorable outcome than the normotensive women. Ours was a retrospective cohort
      study, in which the outcome of 33 hypertensive women with abruptio was compared
      with 138 normotensive women experiencing abruptio placentae. Our results indicate
      that although higher number of hypertensive women with abruptio had a past
      history of hypertension and were more likely to have diabetes (p = 0.05) there
      was no difference found in the grades of abruption or in any other antenatal
      complications between the 2 groups. The hypertensive women were also more likely
      to undergo cesarean section. We did not find any difference in the neonatal
      outcome. Therefore, we conclude that there is no difference in the maternal and
      perinatal outcome between the hypertensive and normotensive women experiencing
      abruptio.

PMID- 9255041
TI  - Intrinsic ureteric involvement by endometriosis: a case report.
AB  - Endometriosis occasionally involves the urinary tract, and a ureteral obstruction
      from this order constitutes a rare variant with serious consequences. Intrinsic
      ureteric involvement by endometriosis is an exceedingly rare event. This case
      report describes intrinsic ureteric involvement by endometriosis. The case
      involved 47-year-old woman, gravida 4, para 2, who had a 4-year history of
      dysmenorrhea and hypermenorrhea. An intravenous pyelogram showed a right
      hydronephrosis. She underwent a total abdominal hysterectomy and a right
      ureteroureterostomy. A pathologic examination revealed complete obstruction of
      the right ureter by intrinsic intramural endometriosis. We conclude that because
      ureteral endometriosis, especially intrinsic endometriosis, is usually silent and
      results in a high rate of renal loss before recognition, physicians should have a
      hightened awareness of this uncommon but serious manifestation of endometriosis.

PMID- 9255042
TI  - DNA analysis of the androgen receptor gene in two cases with complete androgen
      insensitivity syndrome.
AB  - OBJECTIVE: Androgen insensitivity syndrome is an X-linked disorder of sexual
      differentiation resulting from abnormalities of the androgen receptor gene. In
      this study, we analyzed the androgen receptor gene in 2 cases with complete
      androgen insensitivity syndrome (CAIS). METHODS: DNAs were isolated from patients
      with CAIS, and the androgen receptor gene was amplified by a polymerase chain
      reaction. Sequence analysis of the androgen receptor gene was performed. RESULTS:
      In Patient 1, one substitutional mutation [glutamine (CAA) to arginine (CGA) at
      position 194] was identified in exon A, and the premature termination of the
      androgen receptor gene was also demonstrated due to the deletion of one
      nucleotide at the codon in exon C (position 597). In Patient 2, one
      substitutional mutation [arginine (CGC) to cysteine (TGC) at position 855] in
      exon G was identified. This position was located in the hormone-binding domain
      and appeared to be a hot spot of mutations because the mutations at the same
      position have been reported before in several unrelated cases. CONCLUSION: The
      results of this study suggest that these abnormalities might be related to the
      pathogenesis of complete androgen insensitivity syndrome.

PMID- 9255043
TI  - First-trimester detection of amniotic sac in relation to miscarriage.
AB  - OBJECTIVES: The purposes of this study were to make clear the amniotic sac
      detection rate, and to determine whether the detection of an amniotic sac can
      effectively predict miscarriage in the first trimester. STUDY DESIGN: This study
      included 169 normal pregnancy cases and 169 miscarriage cases. Both groups
      consisted of cases with a crown-rump length (CRL) of less than 40 mm. RESULTS: In
      normal pregnancies, the amniotic sac was detectable at a CRL of 7 mm, or longer,
      and its detection rate varied proportionately with the length of the crown rump.
      In the miscarriage cases, the detection of an amniotic sac was possible at a CRL
      of less than 7 mm, and it was independent of the length of the crown rump. At a
      CRL of less than 7 mm, the amniotic sac was detected in 6 miscarriage cases, and
      the amniotic sac size increased after embryonic death in 19 miscarriage cases.
      The amniotic sac detection rate was 38% (65 cases) in all miscarriage cases.
      CONCLUSION: Detection of an amniotic sac might be one of the useful signs
      indicating miscarriage when the CRL is less than 7 mm, at which point detection
      in normal cases is not yet possible.

PMID- 9255044
TI  - Comparative study of different anticonvulsants in eclampsia.
AB  - One hundred eclampsia patients were admitted in this hospital from January 1993
      to November 1993 and they were subjected to different anticonvulsant regimes.
      There were 28 patients in lytic cocktail group, 16 in diazepam group, 16 in
      magnesium sulphate group and 40 patients in phenytoin sodium group. The results
      are compared in every aspect. Feto maternal outcome is best with magnesium
      sulphate regime followed by phenytoin sodium regime. They produce significantly
      better results than lytic cocktail and diazepam.

PMID- 9255045
TI  - Factors influencing an ultrasound-estimated bone mass in postmenopausal women.
AB  - OBJECTIVE: There are various methods for determining bone-mineral density for
      diagnosing osteoporosis. The most accurate method among them is dual-energy X-ray
      absorptiometry (DEXA), and the simplest one utilizes an ultrasound bone
      densitometer. We investigated factors influencing the correlation between bone
      density values determined by dual-energy X-ray absorptiometry and by the use of
      an ultrasound bone densitometer. METHODS: Sixty-seven postmenopausal Japanese
      women aged from 31 to 68 years old were enrolled in the study. Bone-mineral
      densities (BMDs) of the lumbar spine (L2-4) measured by DEXA and broadband
      ultrasound attenuation (BUA) of the right os calcaneus measured by an ultrasound
      bone densitometer were subjected to statistical analysis. RESULTS: Multivariate
      analysis indicated that the patient's exercise history was useful-following the
      number of years since menopause and body weight-for determining lumbar spine bone
      mineral density. The influence of hormone replacement therapy (HRT) on bone mass
      in postmenopausal women is also considered to be marked, but the results of the
      present multivariate analysis showed almost no influence on BUA or the L2-4 BMD.
      CONCLUSIONS: The patient's exercise history should be taken into consideration
      when lumbar spine bone-mineral density is estimated using an ultrasound bone
      densitometer instead of DEXA.

PMID- 9255047
TI  - Comparison of an improved AFP kit with the intra-amniotic PSP dye-injection
      method in equivocal cases of preterm premature rupture of the fetal membranes.
AB  - OBJECTIVE: We developed an improved AFP kit for detecting AFP in leaked amniotic
      fluid. We studied the relationship between the results of the improved AFP kit
      and those of the intra-amniotic PSP dye-injection test (PSP test), and compared
      the results of two tests with the prognosis for subsequent pregnancy outcome, in
      order to know the diagnostic value of the two tests for preterm PROM, especially
      in equivocal cases. METHODS: We compared the results of the AFP kit test with
      those of the PSP test in 8 equivocal cases of preterm PROM (18th to 34th weeks of
      gestation). RESULTS: The results of the AFP kit test coincided with those of the
      PSP test in all 8 equivocal cases of preterm PROM. The 4 cases that tested
      positive resulted in preterm deliveries; and the other 4 cases that tested
      negative resulted in full-term deliveries. CONCLUSION: The use of the AFP kit
      test is useful in assessing the prognosis for subsequent pregnancy in equivocal
      cases of preterm PROM. The rapid and accurate AFP kit test for diagnosing preterm
      PROM can be substituted for the PSP test in bedside and outpatient-clinic
      assessments.

PMID- 9255046
TI  - A phenotypically normal liveborn male after prenatal diagnosis of trisomy 20
      mosaicism.
AB  - We report on a case of prenatally diagnosed trisomy 20 mosaicism. Conventional
      cytogenetic analysis and fluorescence in situ hybridization (FISH) using a
      chromosome 20 specific probe were performed on the lymphocytes and extra
      embryonic tissues after birth. All of them revealed normal karyotypes. The baby
      is developing normally at the age of 2 years.

PMID- 9255048
TI  - Laparoscopic colposuspension in women with previously failed anti-incontinence
      surgery.
AB  - OBJECTIVES: To assess the effectiveness of laparoscopic colposuspension after
      previously failed anti-incontinence surgery. METHODS: Retrospective review of 10
      cases, all with urodynamically proven grade 2 genuine stress incontinence.
      RESULTS: All patients were subjectively cured at 3 months or more follow-up. The
      mean hospital stay was 2.9 days, the mean time until normal voiding was 1.7 days,
      and the mean blood loss was 39 ml. CONCLUSION: Laparoscopic colposuspension may
      be useful after failed anti-incontinence surgery. However, larger numbers are
      needed with objective longer term follow-up.

PMID- 9255049
TI  - Puerperal inversion of the uterus in Nepal: case reports and review of
      literature.
AB  - Retrospective study of 6 cases of puerperal inversion of the uterus is being
      presented from 1975 to 1995 and a review of literature for 20 years of the period
      1975-1995 has been summarised. In the present series, one case with acute
      puerperal inversion of uterus were treated by manual reposition, 2 cases of
      chronic puerperal inversion of uterus was treated surgically by Kustner's vaginal
      approach. Two cases with subacute puerperal inversion of uterus, 1 case of
      chronic puerperal inversion were treated by Haultain and Huntington method. Out
      of 241 cases of uterine inversion obtained from review of literature for last 20
      years, 229 (95%) constituted puerperal and 12 (5%) were non puerperal inversions.
      Among puerperal inversions, 191 (83.4%) cases were of acute type and only 6
      (2.62%) cases were of subacute variety. The chronic puerperal inversion
      constituted 32 (13.9%). Out of 63 cases of uterine inversions in India, maternal
      deaths were reported as 6 (9.5%) but there was no maternal death in the present
      series.

PMID- 9255050
TI  - Structural comparisons of cell organelles and nuclei in rat hepatocytes with
      three different fixation techniques.
AB  - The morphological properties of cell organelles and nuclei in rat hepatocytes
      were compared, when the hepatocytes were either chemically fixed in
      glutaraldehyde and osmium (GA-Os), chemically fixed only in osmium (Os-2h) or
      physically fixed with a microwave-irradiated osmium (Mw-Os) fixative for a short
      duration. Judging from the fine structure, the mitochondria and rER were best
      preserved after physical fixation; because of the smooth surfaces and regular
      open contours, but both organelles shrank in the two chemical fixatives. The
      Golgi complexes and peroxisomes of the hepatocytes were not markedly changed by
      any of the fixative procedures. However the lysosomes and sER were changed to
      some extent after physical fixation. In the nucleus, the two kinds of chromatins
      and the nucleolus were best preserved with physical fixation. In conclusion,
      physical fixation is a very simple and fast procedure that is convenient for
      routine electron microscopy if some attention is paid to the morphological
      changes.

PMID- 9255051
TI  - Histological comparison of morphea and lichen sclerosus et atrophicus.
AB  - Although lichen sclerosus et atrophicus at an early stage and morphea can be
      differentiated clinically and histologically, both diseases at a late stage
      present diagnostic difficulties. In this study, collagen and acid
      glycosaminoglycans in the skin of both morphea and lichen sclerosus et atrophicus
      were examined by polarization microscopy. Picrosirius red and Toluidine blue (pH
      5.8) were used as stains. Under polarized light, the picrosirius red-stained
      collagen fibers appeared green in the papillary and reticular dermis of morphea,
      except the fibers immediately below the epidermis, which appeared orange yellow.
      In lichen sclerosus et atrophicus, the collagen fibers appeared green in the
      reticular dermis at both early and late stage. In the papillary dermis the fibers
      appeared orange at an early stage and greenish orange at a late stage. Toluidine
      blue-stained birefringence in morphea diminished in the presence of MgCl2 at 0.2
      M, in lichen sclerosus et atrophicus in the presence of MgCl2 at 0.3 M.
      Histologically, there were some differences in epidermal changes between the two
      diseases; the epidermis was thick in morphea and thin in lichen sclerosus et
      atrophicus. This difference seems to relate to that in the fibers beneath the
      epidermis.

PMID- 9255052
TI  - Gastric cancer surgery in the octogenarian.
AB  - Seventy-seven octogenarian patients with gastric cancer (Group 1) were
      retrospectively investigated and compared with patients of age from 75 to 79
      years (Group 2). The incidence rates for renal impairment, hepatic impairment,
      and hypoproteinemia, as preoperative complications, were higher in Group 1 than
      in Group 2 (each p < 0.05). The resectability rate was 83% in Group 1 and 89% in
      Group 2. D1 lymphadenectomy was performed for 45% of Group 1 and for 18% of Group
      2 (p < 0.001). On the other hand, D2 lymphadenectomy was performed for 39% of
      Group 1 and for 71% of Group 2 (p < 0.001). A postoperative complication occurred
      in 25% of Group 1 and in 9% of Group 2 (p < 0.01). However, the postoperative
      mortality rate was zero in both groups. The t1 (early cancer) rate was 27% in
      Group 1 and 41% in Group 2 (p < 0.05). On the other hand, t2 was 31% in Group 1
      and 19% in Group 2 (p < 0.05). The overall 5-year-survival rate was 38% in Group
      1 and 48% in Group 2. When causes of mortality other than gastric cancer were
      excluded, the 5-year-survival-rate was 51% in Group 1 and 67% in Group 2 (p <
      0.01).

PMID- 9255053
TI  - Cornell Medical Index score observed among northeast Thai nursing students.
AB  - This report describes physical, psychological and overall health complaints of
      513 female Thai nursing students obtained by using the Cornell Medical Index
      questionnaire (C.M.I.) Thai version. The subjects were 17 to 24 years old in
      their 1st, 2nd, 3rd, or 4th year-class of nursing school in the northeast region
      of Thailand. The Pearson correlation coefficient shows an adequate internal
      consistency of the C.M.I. The observed C.M.I. scores ranged from 1 to 110 with a
      mean of 36.6. The highest percentages of yes-response, among physical and
      psychological complaints, were observed in the questions concerning the
      genitourinary system, and sensitivity respectively. A statistically significant
      inverse correlation was observed between year of nursing school and C.M.I. scores
      in physical, psychological and overall health complaints: the mean C.M.I. score
      on physical and overall health complaints of the 1st and the 3rd year-class
      students were significantly higher than those of the 2nd and the 4th year-class.

PMID- 9255055
TI  - Macrolides reduce the expression of surface Mac-1 molecule on neutrophil.
AB  - Several reports described a favorable effect of "low-dose and long-term"
      erythromycin (EM) on chronic obstructive pulmonary diseases including diffuse
      panbronchiolitis (DPB), although its mechanism still remains obscure. We
      investigated the effect of some macrolides, erythromycin (EM), rokitamycin (RKM),
      midecamycin (MDM) on the expression of neutrophil adhesion molecule Mac-1 using
      LPS-stimulated human whole blood as an experimental vivo model. Samples from six
      healthy volunteer were treated with various concentrations (0.02 ug/ml-20 ug/ml)
      of EM, RKM and MDM for 1 to 3 hs. Surface expression of Mac-1 antigen was
      determined by use of flow-cytometry. When pretreated with EM and MDM for 1 and 3
      hs, significant reduction in Mac-1 expression was observed, but with RKM no
      substantial reduction. These findings indicate that some macrolides such as EM
      suppress the surface expression of Mac-1 on neutrophil and may alleviate local
      alveolar injury in chronic pulmonary diseases.

PMID- 9255054
TI  - Rapid uptake and phosphorylation of D-mannose, and limited D-mannose 6-phosphate
      isomerization in the glycolytic pathway of bloodstream forms of Trypanosoma
      brucei gambiense.
AB  - Bloodstream forms of the parasitic protozoa Trypanosoma brucei gambiense derive
      all of needed energy through an unusual glycolysis. In an earlier study, we
      showed that D-mannose specifically inhibited the growth of bloodstream forms of
      T. b. gambiense. We investigated D-mannose transport into the T. b. gambiense
      bloodstream forms and its metabolism in the initial phase of the glycolytic
      pathway. D-Mannose was transported rapidly into the bloodstream forms of T. b.
      gambiense (K(m) = 378 microM), and D-glucose competitively inhibited D-mannose
      uptake. D-Mannose and D-glucose are transported into bloodstream trypanosomes by
      the same carrier. Hexokinase from the bloodstream trypanosomes could convert D
      mannose to D-mannose 6-phosphate (K(m) = 155.8 microM; Vmax = 0.93 mumol/min/mg
      protein); with kinetic properties very similar to D-glucose phosphorylation (K(m)
      = 199.4 microM; Vmax = 1.15 mumol/min/mg protein). D-Mannose 6-phosphate could be
      further metabolized in the glycolytic pathway. However, the metabolic rate was
      extremely slow, and D-mannose 6-phosphate accumulated in the glycosomes. D
      Mannose may cause growth inhibition of bloodstream trypanosomes through an
      extremely high concentration of D-mannose 6-phosphate in the glycosomes.

PMID- 9255056
TI  - Properties of ligand-gated potassium channels in neurons of rat dorsolateral
      septal nucleus.
AB  - Properties of ligand-gated K+ channels were examined in neurons of rat
      dorsolateral septal nucleus (DLSN). Application of muscarine (30 microM), 5
      hydroxytryptamine (5-HT, 10 microM), adenosine (100 microM), baclofen (10 microM)
      and norepinephrine (NE, 10 microM) to DLSN neurons caused hyperpolarizing
      responses associated with decreased membrane resistance. Hyperpolarizations
      induced by muscarine increased their amplitudes at membrane potential between -70
      and -50 mV. Baclofen- and NE-induced hyperpolarizations were less sensitive to
      voltage. The agonist-induced hyperpolarizations decrease in amplitudes and
      reversed at a membrane potential between -90 and -100 mV. Ba2+ (1 mM) blocked all
      agonist-induced hyperpolarizations in DLSN neurons. Tetraethylammonium (TEA, 3
      mM) blocked the muscarine-induced hyperpolarization but not the
      hyperpolarizations induced by the other agonists. Extracellular Cs+ and
      glibenclamide did not block the agonist-induced hyperpolarizations. These results
      suggest that muscarine, 5-HT, adenosine, baclofen and NE cause the
      hyperpolarization by increasing the activity of Ba(2+)-sensitive K+ channels,
      probably the GTP-binding protein (G-protein) activated inward rectifier K+ (GIRK)
      channels in DLSN neurons.

PMID- 9255057
TI  - Hemarthrosis of the knee and bone contusion.
AB  - We present five patients with acute traumatic hemarthrosis of the knee who also
      had hemorrhage within the bone marrow around the knee detected by magnetic
      resonance imaging. No additional bony, ligamentous, meniscal or osteochondral
      injuries were evident from clinical examination, initial and repeated plain
      radiographs, or magnetic resonance imaging. The main symptoms were sharply
      localized pain and tenderness of the contused area. When hemarthrosis was
      demonstrated at the first office visit, three cases had fat droplets in the
      blood. Two patients with hemarthrosis of the knee undergoing arthroscopy showed
      no obvious lesions of intra-articular structures. Instead they showed congestion
      of the joint capsule located in accordance with the traumatic episode. Magnetic
      resonance imaging demonstrated marrow abnormalities as diffusely low and high
      signal intensity areas in T1-weighted and T2-weighted images, respectively, in
      locations consistent with the traumatic episode and the symptoms. These
      disappeared within an average of 13 weeks (range in 4 cases, 12 to 16 weeks).
      These findings were considered diagnostic of bone contusion. Symptom duration was
      about 2 weeks in all cases. In conclusion the clinician should consider the
      possibility of coexisting bone contusion in cases of acute traumatic hemarthrosis
      of the knee with no evidence of bone or intra-articular lesions on clinical
      examination and conventional radiographs.

PMID- 9255058
TI  - Thymolipoma: clinical and pathological features--report of three cases and review
      of literature.
AB  - We report three recently resected cases of thymolipoma. Two cases (case 2 and 3)
      were female and the other (case 1) was male. The age of these three were 41
      years, 63 years, and 29 years, respectively. While two cases (case 1 and 2) were
      asymptomatic, the other (case 3) had associated myasthenia gravis. Preoperative
      examination in each case was performed using chest CT scan or chest MRI, or both.
      Only one case (case 1) was diagnosed as thymolipoma preoperatively, and this was
      by a chest MRI showing the mass in continuity with the thymus. The diagnosis of
      each lesion was confirmed histologically by their composition of lobules of
      mature adipose tissue with minute islands of thymic tissue consisting of
      epithelial cells, lymphocytes, and Hassall's bodies.

PMID- 9255059
TI  - A rare case of the right-sided aortic arch that has the right subclavian artery
      as the last branch.
AB  - This report describes a rare case of the right-sided aortic arch with the right
      subclavian artery as the last branch, which was encountered in a Japanese male
      cadaver in the dissecting room at Kurume University School of Medicine in 1995.
      In this subject, the ascending aorta arose from the left ventricle and ascended
      obliquely, curving forward and to the right, and became the right-sided aortic
      arch. The aortic arch passed upwards, reaching a summit at the level of the third
      thoracic vertebral body, then curved dorsally. The left brachiocephalic, the
      right common carotid and the right subclavian arteries came off the aortic arch
      in that order. After the right subclavian artery, the aortic arch dilated and
      formed the aortic diverticulum behind the trachea and the esophagus. The right
      thoracic aorta, a continuation of the aortic arch, descended to the right of the
      vertebral column. This case is a type M anomaly according to the Adachi-Williams
      Nakagawa's classification, and is the twelfth case with this type of vascular
      variation to be reported in Japan.

PMID- 9255060
TI  - A case of horseshoe kidney.

PMID- 9255061
TI  - Telomerase and telomere-binding proteins: controlling the endgame.

PMID- 9255062
TI  - A measure of success in fold recognition.
AB  - Prediction of protein structure by fold recognition, or threading, was recently
      put to the test in a 'blind' structure prediction experiment, CASP2. Thirty-two
      teams from around the world participated, preparing predictions for 22 different
      'target' proteins whose structures were soon to be determined. As experimental
      structures became available, we, as organizers of the threading competition,
      computed objective measures of fold-recognition specificity and model accuracy,
      to identify and characterize successful predictions. Here, we present a brief
      summary of these prediction evaluations, a tally of 'correct' predictions and a
      discussion of factors associated with correct predictions. We find that threading
      produced specific recognition and accurate models whenever the structural
      database contained a template spanning a large fraction of target sequence.
      Presence of conserved sequence motifs was helpful, but not required, and it would
      appear that threading can succeed whenever similarity to a known structure is
      sufficiently extensive.

PMID- 9255063
TI  - Three-dimensional NMR structure of a self-folding domain of the prion protein
      PrP(121-231)

PMID- 9255064
TI  - A shared domain between a spindle assembly checkpoint protein and Ypt/Rab
      specific GTPase-activators.

PMID- 9255065
TI  - Novel protein serine/threonine phosphatases: variety is the spice of life.
AB  - The dephosphorylation of proteins on serine and threonine residues is a major
      mechanism of cellular regulation. Many novel protein serine/threonine
      phosphatases in the PPP family have recently been discovered and the insights
      that have been gained into their different functions are summarised in this
      review.

PMID- 9255066
TI  - Molecular mechanisms of blood vessel formation.
AB  - The formation of new blood vessels, angiogenesis, is a tightly regulated process.
      Extracellular angiogenic inducers stimulate the migration and proliferation of
      endothelial cells, while negative regulators counteract this effect. Changes in
      the relative balance of inducers and inhibitors activate the 'angiogenic switch',
      before stabilizer molecules activate the maturation of nascent blood vessels.

PMID- 9255067
TI  - Guiding ribose methylation of rRNA.
AB  - Eukaryotic rRNAs contain a complex set of ribose-methylated nucleotides. Why are
      these nucleotides modified and how are they selected? A large family of small
      nucleolar RNAs (snoRNAs) with long complementarities to sites of rRNA methylation
      has been recently found to guide such modifications, opening up a direct approach
      to the study of their elusive function. Ribose methylation can also be targeted
      to non-rRNA sequences by tailored snoRNA guides, possibly providing a highly
      selective tool for altering gene expression at the post-transcriptional level.

PMID- 9255068
TI  - RNA seeing double: close-packing of helices in RNA tertiary structure.
AB  - Structured RNA molecules play essential roles in RNA processing, chromosome
      maintenance and protein biosynthesis. RNA necessarily uses different strategies
      than proteins for folding and assembly of complex architectures. The RNA-folding
      problem is largely an issue of helical packing: how does RNA organize and pack
      short, double-helical segments to produce active sites and recognition motifs for
      proteins? Noncanonical base pairs, metal ions and 2'-hydroxyl groups are key
      elements in RNA higher-order structure formation.

PMID- 9255069
TI  - Phosphoinositide 3-kinases: a conserved family of signal transducers.
AB  - Phosphoinositide 3-kinases (PI3Ks) generate lipids that are implicated in
      receptor-stimulated signalling and in the regulation of membrane traffic. Several
      distinct classes of PI3Ks have now been identified that have been conserved
      throughout eukaryotic evolution. Potential signalling pathways downstream of
      PI3Ks have been elucidated and PI3K function is now being characterised in
      several model organisms.

PMID- 9255071
TI  - WebMol--a Java-based PDB viewer.

PMID- 9255070
TI  - Shearing DNA for genomic library construction.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussion in the newsgroup bionet.molibio.methds-reagnts, available on the
      internet. This month's column discusses the pros and cons of various techniques
      used to shear DNA for shotgun cloning. For details on how to partake in the
      newsgroup, see the accompanying box.

PMID- 9255072
TI  - Reflections on the days of ribosome reconstitution research.

PMID- 9255073
TI  - Achieving best practice in maternity care.

PMID- 9255074
TI  - Perinatal audit in Europe.

PMID- 9255075
TI  - Has screening for cervical cancer been successful?

PMID- 9255076
TI  - Who understands the menopause?

PMID- 9255077
TI  - Management of fetal choroid plexus cysts.

PMID- 9255078
TI  - The HELLP syndrome.

PMID- 9255080
TI  - Effects of magnesium sulphate on the noradrenaline-induced cerebral
      vasoconstrictor and pressor responses in the goat.
AB  - OBJECTIVE: To examine the ability of magnesium sulphate to counteract the
      noradrenaline-induced cerebral vasoconstrictor and pressor responses in goats by
      using both in vivo and in vitro techniques. DESIGN: Cerebral blood flow was
      measured in vivo by means of an electromagnetic flow probe around the internal
      maxillary artery. Isometric tension was recorded in vitro from rings of goat
      middle cerebral artery maintained in an organ bath. RESULTS: 1. In vivo.
      Continuous infusion of noradrenaline (10 micrograms/min) directly into the
      cerebral arterial supply elicited sustained decrease in cerebral blood flow (61%
      [SEM 3] of control values) and increase in cerebral vascular resistance (178%
      [SEM 9] of control values). Magnesium sulphate, injected directly into the
      cerebral arterial supply (10-300 mg) or infused intravenously (0.3 g and 3 g
      during 15 min) at the noradrenaline-induced steady state, increased cerebral
      blood flow by decreasing cerebral vascular resistance in a dose-dependent manner.
      A similar result was obtained when intravenous magnesium sulphate (3 g/15 min)
      was tested against the cerebral vasoconstrictor and pressor responses induced by
      intravenous infusion of noradrenaline (30 micrograms/min). 2. In vitro. When
      compared with the response obtained in a control medium (1 mmol/L Mg2+), 10
      mmol/L Mg2+ significantly inhibited the maximum contraction elicited by
      noradrenaline (10(-8) to 3 x 10(-3) mol/L) from 45% [SEM 4] to 26% [SEM 4].
      CONCLUSIONS: Magnesium sulphate reverses the noradrenaline-induced cerebral
      vasoconstrictor and pressor responses by a direct inhibitory action of Mg2+ on
      the actions of noradrenaline in the cerebral and peripheral vascular beds, which
      leads to a decrease in vascular resistance. These results could explain, at least
      in part, the beneficial effects of magnesium sulphate in the management of
      preeclampsia and eclampsia.

PMID- 9255081
TI  - Maternal middle cerebral artery velocimetry in normal pregnancy and postpartum.
AB  - OBJECTIVE: To study changes throughout gestation and the puerperium of middle
      cerebral artery flow velocity waveforms obtained by transcranial Doppler
      ultrasound. DESIGN: Prospective, observational study. SETTING: John Radcliffe
      Maternity Hospital, Oxford, UK. PARTICIPANTS AND METHODS: Middle cerebral artery
      velocities were measured by transcranial Doppler ultrasound in 25 nonpregnant
      women, 22 women longitudinally followed throughout pregnancy and 21 women
      serially studied from delivery until the late puerperium. MAIN OUTCOME MEASURES:
      Transcranial Doppler changes in pregnancy and the puerperium. RESULTS: The
      transcranial Doppler ultrasound measurements showed good reproducibility. Signals
      from one middle cerebral artery could not be obtained in 4.6% of the
      examinations, but otherwise readings were similar on both sides. Women in the
      second half of pregnancy had lower middle cerebral artery mean velocities than
      nonpregnant women. Velocities decreased with advancing gestation but increased in
      the immediate puerperium to levels comparable to those found in nonpregnant
      women. CONCLUSIONS: Transcranial Doppler ultrasound is a noninvasive technique
      suitable for studying maternal cerebral haemodynamics in pregnancy and
      postpartum. Middle cerebral artery mean velocity decreased with advancing
      gestation and increased to nonpregnant values in the immediate puerperium. These
      physiological changes need to be considered when comparing data with measurements
      taken in abnormal pregnancy states.

PMID- 9255079
TI  - Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised
      controlled multicentre trial.
AB  - OBJECTIVE: To determine whether treatment with ampicillin and metronidazole in
      women with threatened idiopathic preterm labour will prolong the gestation and
      reduce maternal and neonatal infectious morbidity. DESIGN: Randomised controlled
      double-blind trial. SETTING: Six obstetric departments in the Copenhagen area.
      POPULATION: One hundred and twelve women with singleton pregnancies, with
      threatened idiopathic preterm labour and intact amniotic membranes at 26 to 34
      weeks of gestation. METHODS: Random allocation to eight days intravenous and oral
      treatment with ampicillin and metronidazole, or placebo. MAIN OUTCOME MEASURES:
      Number of days from admission to delivery, gestational age at delivery, rates of
      preterm delivery, low birthweight, maternal infections and neonatal infections.
      RESULTS: Treatment with ampicillin and metronidazole was associated with a
      significant prolongation of pregnancy (admission to delivery 47.5 days versus 27
      days, P < 0.05), higher gestational age at delivery (37 weeks versus 34 weeks, P
      < 0.05), decreased incidence of preterm birth (42% versus 65%, P < 0.05), and
      lower rate of admission to neonatal intensive care unit (40% versus 63%, P <
      0.05), when compared with placebo treatment. Antibiotic treatment had no
      significant effects on infectious morbidity. CONCLUSIONS: Treatment with
      ampicillin and metronidazole in women with threatened idiopathic preterm labour
      significantly prolonged the gestation, but had no effects on maternal and
      neonatal infectious morbidity.

PMID- 9255082
TI  - Effect of location of the sensor on reflectance pulse oximetry.
AB  - OBJECTIVE: The influence of the location of the sensor on reflectance pulse
      oximetry during fetal monitoring in labour was investigated using the newborn
      infant as a model. METHODS: Seven healthy infants were studied between 19 and 48
      hours after term delivery. Recordings of reflectance pulse oximetry were obtained
      from eight different sites on the infant's head. The relative changes in red to
      infrared light (R/IR) were determined. In pulse oximetry R/IR values are
      converted to arterial oxygen values by means of an empirically derived
      calibration curve. RESULTS: Significantly lower R/IR values were found at the
      forehead compared with the fontanelle, the parietal and occipital position, and
      the temporal area. Conversion to oxygen saturation values revealed a difference
      of up to 13.4% in oxygen saturation between the forehead and the occipital area.
      CONCLUSION: Assuming that the arterial blood oxygen saturation did not change
      substantially, our findings indicate that in reflectance pulse oximetry there is
      no unique relation between R/IR and arterial oxygen saturation. The differences
      in reflectance pulse oximetry at the various sites are explained by differences
      in optical properties (scattering and absorption) of the tissue underneath the
      sensor. These will affect the red and infrared light reaching the detectors in a
      different way, and consequently R/IR changes. Because during intrapartum
      monitoring exact positioning of the sensor on the fetal head is usually
      impossible, the accuracy of fetal reflectance pulse oximetry is impaired.

PMID- 9255083
TI  - The changing pattern of eclampsia over a 60-year period.
AB  - OBJECTIVE: To determine changes in the incidence and pattern of eclampsia within
      the same geographical area over a 60-year period. DESIGN: A retrospective,
      descriptive study of 1259 consecutive women classified, at the time, as having
      had an eclamptic convulsion between the years 1931 and 1990. SETTING: A large
      city centre teaching hospital and the surrounding catchment area. MAIN OUTCOME
      MEASURES: The changes in the incidence and timing of the convulsion and the
      outcomes for the mother and baby. RESULTS: Over the study period, the incidence
      of eclampsia fell by more than 90%, from 74.1/10,000 in the 1930s to 7.2/10,000
      in the 1980s. Most of the reduction occurred over the first four decades, with
      little change in the last 20 years. Overall, 44% of the cases of eclampsia
      occurred in the antenatal period, 33% intrapartum and 23% postpartum. Since the
      biggest decreases were seen in the incidence of antenatal and particularly
      intrapartum eclampsia, there has been a relative increase in the proportion of
      eclampsia occurring postpartum. Maternal death from eclampsia occurred in 15.1%
      of cases between 1931 and 1940, 13.4% between 1941 and 1950, but fell
      dramatically to < or = 3.9% after 1950. There has been no maternal death since
      1964. Apart from the first decade, postpartum eclampsia was associated with
      significantly less risk of death to the mother throughout the study period.
      Perinatal death rate has fallen steadily from 432.6/1000 cases of eclampsia
      between 1931 and 1940 over the first three decades, to 168.7/1000 between 1961
      and 1970. There has been little change since, although a lower proportion of
      neonatal deaths occurred as stillbirths. CONCLUSIONS: We found a significant
      reduction in both the incidence of eclampsia and associated morbidity in this
      population over the last 60 years. This has occurred in association with the
      introduction of the National Health Service, widespread antenatal care for all
      and a general improvement in health and welfare. Any further reduction in the
      incidence in the UK may be difficult to achieve. Since the incidence of eclampsia
      is now low, efforts should perhaps be directed at minimising the morbidity
      associated with severe pre-eclampsia rather than prevention of convulsions.

PMID- 9255084
TI  - Women's health in midlife: the influence of the menopause, social factors and
      health in earlier life.
AB  - OBJECTIVE: To describe the health symptoms of a large representative sample of
      British women at age 47 years, and to examine the influence of the menopause
      allowing for social factors and health in earlier adult life. DESIGN: A national
      prospective birth cohort study. Information on health problems, menstrual cycle,
      use of hormone replacement therapy and life stress at 47 years was collected
      using a postal questionnaire. Information on health, smoking behaviour and
      educational attainment earlier in life had been collected at previous home
      visits. SETTING: England, Scotland and Wales. POPULATION: A general population
      sample of 1498 women, 84% of those sent a questionnaire. MAIN OUTCOME MEASURE:
      Twenty self-reported health symptoms over the previous 12 months. RESULTS: Women
      who had experienced an early natural menopause had a strongly raised risk of
      vasomotor symptoms (hot flushes or night sweats), sexual difficulties (vaginal
      dryness or difficulties with intercourse) and trouble sleeping. However, there
      was little or no excess risk of other somatic or psychological symptoms. In
      contrast, all types of symptoms were more common among women who had had a
      hysterectomy or were users of hormone replacement therapy. Women with the least
      education, stressful lives, or a previous history of poor physical and
      psychological health at age 36 also reported more symptoms at 47 years compared
      with other women, but adjustment for these factors in a logistic regression model
      did not affect the relations between symptoms and current menopausal status. For
      vasomotor symptoms, postmenopausal women had an adjusted odds ratio of 4.7 (95%
      CI 2.6-8.5) and perimenopausal women had an adjusted odds ratio of 2.6 (95% CI
      1.9-3.5) compared with premenopausal women. Corresponding adjusted odds ratios
      for sexual difficulties were 3.9 (95% CI 2.1-7.1) and 2.2 (95% CI 1.4-3.2), and
      for trouble sleeping were 3.4 (95% CI 1.9-6.2) and 1.5 (95% CI 1.1-2.0).
      CONCLUSIONS: Specific symptoms were clearly associated with the natural
      menopause. More general health concerns were common among women in middle life,
      particularly among those with stressful lives, or those who had had a
      hysterectomy or started taking hormone replacement therapy before they were
      postmenopausal. Appropriate advice and support needs to be easily accessible.

PMID- 9255085
TI  - Magnetic resonance imaging of the uterus after endometrial resection.
AB  - OBJECTIVE: Despite the increasing popularity of endometrial resection for the
      treatment of menstrual problems, the long term sequelae of this procedure are
      poorly recognised. As diagnostic hysteroscopy following endometrial resection is
      frequently unrewarding and transvaginal ultrasound is incapable of detecting
      subtle changes in endometrial morphology, magnetic resonance imaging was employed
      to evaluate the uterus. DESIGN: Retrospective study of unselected post-operative
      women. METHODS: Fifty-nine women, of whom 22 were amenorrhoeic, were studied a
      mean number of 34 months after endometrial resection, using a 1.5 Tesla magnetic
      resonance imaging system with a pelvic phased array coil for signal reception. T2
      weighted FSE images were acquired through the long and short uterine axis and
      volumetric assessment of each uterine layer performed using an ISG Allegro
      workstation. MAIN OUTCOME MEASURES: The location and volume of residual
      endometrium, the volume of junctional zone and myometrial tissue, and the
      presence of additional intrauterine and pelvic pathology were recorded. RESULTS:
      Residual endometrium was demonstrated in all except three amenorrhoeic women,
      with a similar mean volume present in menstruating and amenorrhoeic groups.
      Additional findings included adenomyosis, haematometra, fallopian tube dilatation
      and free intraperitoneal fluid. CONCLUSIONS: The majority of amenorrhoeic and all
      menstruating women have residual endometrium after endometrial resection. The
      lack of communication of islands of residual endometrium with the uterine cavity
      results in haematometra formation, fallopian tube dilatation and possibly free
      intraperitoneal fluid.

PMID- 9255086
TI  - Bladder visualisation as a prognostic sign in oligohydramnios-polyhydramnios
      sequence in twin pregnancies treated using therapeutic amniocentesis.
AB  - Oligohydramnios-polyhydramnios sequence in twin pregnancies may be managed by
      aggressive amniocentesis and is described in nine consecutive cases. In four of
      the nine pregnancies both twins survived, one pair died in the neonatal period,
      and the other four pairs all suffered intrauterine death. The median number of
      amnioreductions performed was five (range 2-7). In this series the reaccumulation
      of urine in the bladder of the 'stuck twin' was a predictive prognostic marker of
      survival in both twins, with a sensitivity and specificity of 100%.

PMID- 9255087
TI  - Zoonotic and viral infection in fetal loss after 12 weeks.
AB  - One hundred and thirty-six women from an urban, rural and farming community were
      recruited to a study of infectious causes of midtrimester miscarriage (n = 85),
      stillbirth (n = 32), or termination for developmental (n = 17) or chromosomal (n
      = 2) abnormalities. No woman had evidence of acute infection with toxoplasma,
      listeria, leptospira or Chlamydia psittaci (ovine enzootic abortion). One woman
      had midtrimester miscarriage associated with primary cytomegolovirus infection
      and five women had evidence of parvovirus B19 infection, although fetal infection
      was not proven. Zoonoses were not identified as a cause of fetal loss or
      malformation in this at-risk population, but parvovirus B19 was a significant
      cause of midtrimester fetal loss.

PMID- 9255088
TI  - Maternal serum inhibin-A in pregnancies complicated by insulin dependent diabetes
      mellitus.
AB  - We have examined whether insulin dependent diabetes mellitus (IDDM) affects
      maternal serum levels of inhibin-A, a recently described prenatal marker of
      Down's syndrome, by comparing levels in 169 women with IDDM with levels in 432
      nondiabetic pregnant women between 15 and 20 weeks of gestation. There was a
      small but significant increase in the inhibin-A level in the diabetic women only
      when levels were corrected for maternal weight: median MoM 1.17 (P < 0.01 vs
      controls, Student's t test). The underlying mechanism for this elevation in
      pregnancies complicated by IDDM currently remains obscure.

PMID- 9255089
TI  - Menstrual characteristics associated with endometriosis.
AB  - This case-controlled study investigates whether the presence of menstrual
      characteristics, which may increase the exposure of the peritoneal cavity to
      retrograde menstruation, increases the risk of developing endometriosis. The
      menstrual characteristics considered were 1. age at menarche of less than 12
      years, 2. duration of menstrual flow greater than five days and 3. menstrual
      cycle lengths of < 28 days. The frequency with which these menstrual
      characteristics occurred in 305 women with proven endometriosis was compared with
      their frequency in 305 age-matched women without endometriosis. Adjusting for the
      confounding factors of parity, age at first childbirth and social class, the only
      menstrual characteristic that was significantly associated with endometriosis was
      menstrual cycle lengths of less than 28 days (odds ratio 1.83; 95% confidence
      intervals 1.60-2.55). There was insufficient evidence to conclude that the
      presence of menstrual characteristics which may increase the exposure of the
      peritoneal cavity to retrograde menstruation, increase a women's risk of
      developing endometriosis. The association of short menstrual cycle lengths with
      endometriosis may have been consequential rather than causal.

PMID- 9255090
TI  - Acute uterine inversion: a new technique of hydrostatic replacement.

PMID- 9255091
TI  - Recurrent idiopathic ovarian hyperstimulation syndrome in pregnancy.

PMID- 9255092
TI  - Laparoscopic cornuostomy in the treatment of interstitial pregnancy with
      subsequent hysterosalpingography.

PMID- 9255093
TI  - The whole duty of obstetricians.

PMID- 9255094
TI  - The case against new reproductive technologies in developing countries.

PMID- 9255095
TI  - The case against new reproductive technologies in developing countries.

PMID- 9255096
TI  - Serum levels of the tumour-associated trypsin inhibitor in patients with
      endometriosis.

PMID- 9255097
TI  - A comparison of the inactive urinary kallikrein: creatinine ratio and the
      angiotensin sensitivity test for the prediction of pre-eclampsia.

PMID- 9255098
TI  - Estimation of fetal lung volume using enhanced 3-dimensional ultrasound: a new
      method and first result.

PMID- 9255099
TI  - VEGF mRNA levels in placentae from pregnancies complicated by pre-eclampsia.

PMID- 9255100
TI  - Posterior colporrhaphy: its effect on bowel and sexual function.

PMID- 9255101
TI  - A double-blind randomised controlled trial of the effects of medroxyprogesterone
      acetate on bone density of women taking oestrogen replacement therapy.

PMID- 9255102
TI  - Gynaecological cancer services: time for change.

PMID- 9255103
TI  - The growth of paediatric rheumatology.

PMID- 9255104
TI  - Why does osteoarthritis of the knee hurt--sometimes?

PMID- 9255105
TI  - Effects of transforming growth factor beta on the production of prostaglandin E
      and caseinase activity of unstimulated and interleukin 1-stimulated human
      articular chondrocytes in culture.
AB  - Transforming growth factor beta (TGF beta) has previously been shown to have
      actions on chondrocytes and cartilage both in vitro and in vivo which suggest a
      role in connective tissue repair. In particular, some of its actions have been
      shown to be antagonistic to those of interleukin 1 (IL-1). In this study, the
      effects of TGF beta on prostaglandin E (PGE) production and caseinase activity,
      in the presence and absence of IL-1, in human articular chondrocytes were
      investigated. TGF beta 1 and TGF beta 2 were shown to modulate IL-1 beta
      stimulated PGE production and caseinase activity. Both TGF beta 1 and beta 2
      inhibited IL-1 beta-stimulated PGE production in the absence of serum and
      augmented it in the presence of serum. TGF beta 1 and TGF beta 2 inhibited IL-1
      stimulated caseinase activity with and without serum. In general, the TGF beta s
      had little or no effect on basal PGE or caseinase levels. TGF beta s may be
      important modulators of chondrocyte metabolism, their effects on PGE production
      may depend on cytokine interactions; furthermore, their effects on caseinase
      activity may help prevent cartilage breakdown.

PMID- 9255106
TI  - Selective induction of the secretion of cathepsins B and L by cytokines in
      synovial fibroblast-like cells.
AB  - We have investigated the potent influence of some cytokines, tumour necrosis
      factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), basic fibroblast
      growth factor (bFGF) and interferon-gamma (IFN-gamma), on the secretion of
      cysteine proteinases (cathepsins B and L) by cultured synovial fibroblast-like
      cells from patients with rheumatoid arthritis (RA). After treatment of synovial
      fibroblast-like cells with cytokines, culture media were evaluated for cathepsins
      B and L by enzyme immunoassays, and for cathepsin B and L activities using the
      enzymatic substrates. Z-Phe-Arg-AMC and Z-Arg-Arg-AMC, and specific inhibitors.
      Treatment of synovial fibroblast-like cells with TNF-alpha or PDGF resulted in a
      marked increase in cathepsin B secretion. Moreover, after prolonged PDGF
      treatment, the amount of secreted cathepsin B returned to the low control level.
      In contrast, bFGF led to increased cathepsin L secretion. IFN-gamma induced both
      cathepsin B and L secretion. Our results show that cytokines induce a selective
      secretion of cathepsins B and L by synovial fibroblast-like cells. This selective
      effect of cytokines on the secretion of cysteine proteinases suggests that
      synovial fibroblast-like cell-mediated articular degradation is a highly
      regulated process.

PMID- 9255107
TI  - Gelatinase B in chronic synovitis: immunolocalization with a monoclonal antibody.
AB  - Gelatinase B is a matrix metalloproteinase (MMP-9) involved in the remodelling of
      extracellular matrices of connective tissues. With the use of specific monoclonal
      antibodies against human gelatinase B, the producer cell types were pinpointed in
      histopathological sections of a number of arthritic diseases. In cases of acute
      joint trauma, chondromatosis, villonodular synovitis and a cyst of a bursa, high
      numbers of strongly immunopositive neutrophils were observed in addition to
      weaker staining macrophages. Activated macrophages with giant cell morphology
      clearly stained with the gelatinase B-specific monoclonal antibody in the case of
      villonodular synovitis and in an epidermoid cyst. However, in the sections from
      patients with rheumatoid arthritis, no immunostaining was seen. In other cases of
      chronic synovitis, however, within the lymphocyte nodular aggregates a strong
      gelatinase B expression was observed in morphologically identified dendritic
      cells. In conclusion, gelatinase B production in joint disease seems to be
      predominantly by neutrophils and cell types of the macrophage/antigen-presenting
      cell lineage.

PMID- 9255108
TI  - Expression of the cutaneous lymphocyte antigen and its counter-receptor E
      selectin in the skin and joints of patients with psoriatic arthritis.
AB  - We have investigated whether the skin-homing T lymphocytes identified by the
      cutaneous lymphocyte antigen (CLA) are increased in the synovial membrane of
      patients with psoriatic arthritis. Twenty-six synovial samples (13 psoriatic
      arthritis, seven rheumatoid arthritis, six osteoarthritis) were obtained from
      involved knees. Lesional skin biopsies were taken from nine of the patients with
      psoriatic arthritis and six patients with psoriasis alone. All samples were
      single- and dual-stained for CLA and CD3 (to identify T lymphocytes) using HECA
      452 (anti-CLA) and anti-CD3 monoclonal antibodies. E-selectin expression was also
      determined. The percentage of dual-stained lymphocytes was significantly greater
      in psoriatic skin than in synovium (P < 0.001) and similar between psoriatic and
      rheumatoid synovium. There was no significant difference in the percentages of
      CLA-positive cells in psoriatic skin in patients with psoriatic arthritis
      compared with psoriasis alone. The intensity of endothelial E-selectin expression
      was significantly greater in skin psoriasis than in synovium (P < 2 x 10(-5)),
      and rheumatoid synovium had significantly greater expression than psoriatic
      synovium (P < 0.05). However, there was no significant correlation between E
      selectin expression and the percentages of CLA-positive lymphocytes. This study
      provides further evidence that the CLA antigen is enriched on skin-homing
      lymphocytes. Conversely, the link between skin and joint inflammation in
      psoriatic arthritis does not seem to be explained by increased trafficking of CLA
      T cells to psoriatic synovium.

PMID- 9255109
TI  - Macrophage targeting with 99mTc-labelled J001 for scintigraphic assessment of
      experimental osteoarthritis in the rabbit.
AB  - The potential of scintigraphy with technetium 99m-labelled J001 (99mTc-J001) to
      detect synovitis was studied in 15 rabbits with osteoarthritis (OA) of the right
      knee (section of cruciate ligaments), in five sham-operated rabbits and in four
      non-operated rabbits. J001 is a non-pyrogenic, acylated poly (1,3) galactoside
      isolated from the membrane of a non-pathogenic strain of Klebsiella pneumoniae
      which is able to bind selectively to macrophages via the binding to CD11b and
      CD14 molecules. The results of 99mTc-J001 scintigraphy were compared with those
      of scintigraphy with 99mTc-labelled methylene diphosphonate (99mTc-MDP) and GC
      APG (a derivative of J001 unable to bind macrophages in vitro). The mean
      scintigraphic ratios (diseased healthy knee) of 99mTc-J001 were significantly
      higher in OA rabbits than in sham- and non-operated rabbits, from as early as day
      18 until day 90. 99mTc-J001 scintigraphy demonstrated earlier increased uptake
      than 99mTc-MDP scintigraphy. The mean scintigraphic ratios of 99mTc-J001 were
      significantly higher than those of 99mTc-GC-APG (which remained normal) in OA
      rabbits. The normal scintigraphic ratios of 99mTc-J001 in sham-operated and non
      operated rabbits, as well as of 99mTc-GC-APG in OA rabbits, suggested that the
      increased uptake demonstrated with 99mTc-J001 in OA rabbits, as early as day 18
      corresponded to imaging of synovitis via elective macrophage targeting. These
      results showed that 99mTc-J001 scintigraphy should be a specific method of
      detecting synovitis in OA.

PMID- 9255110
TI  - Ligase chain reaction in detection of Chlamydia DNA in synovial fluid cells.
AB  - Synovial fluid cells from 12 patients with reactive arthritis (ReA) triggered by
      Chlamydia trachomatis were studied for the presence of Chlamydia DNA using the
      ligase chain reaction (LCR) LCx (Abbott) and the polymerase chain reaction (PCR)
      Amplicor (Roche). In addition, peripheral blood leucocytes from 11 of these
      patients were analysed by LCR. As controls, seven patients with newly diagnosed
      rheumatoid arthritis (RA) were included. Chlamydia trachomatis DNA was detectable
      by LCR in samples of synovial fluid cells from 4/12 patients with C. trachomatis
      triggered ReA, and in none by PCR. Chlamydia trachomatis DNA was not detectable
      in the synovial fluid cells of the seven RA patients by either method, neither
      was C. trachomatis DNA detectable in the peripheral blood leucocytes of the ReA
      patients (0/11) or controls (0/6) by LCR. The LCR technique may be useful in the
      demonstration of Chlamydia DNA in synovial fluid cells.

PMID- 9255111
TI  - The outcome of ankylosing spondylitis: a study of 100 patients.
AB  - The outcome was studied in 100 patients with adult-onset primary ankylosing
      spondylitis (AS). After a mean disease duration of 16 yr, 51.5% of the patients
      were employed in full-time work. Cessation of work occurred at a mean disease
      duration of 15.6 yr, and was significantly associated with female sex, low levels
      of education, acute anterior uveitis, 'bamboo spine' and the co-existence of non
      rheumatic diseases. Functional outcome was studied by analysing activities of
      daily living, and revealed similar findings in males and females. Most of the
      loss of function occurred during the first 10 yr of disease, and correlated
      significantly with the occurrence of peripheral arthritis, spinal X-ray changes
      of AS and development of 'bamboo spine'. After > 20 yr of disease, > 80% of the
      patients still complained of daily pain and stiffness, and > 60% reported daily
      use of drugs.

PMID- 9255112
TI  - Outcome of planned pregnancies in systemic lupus erythematosus: a prospective
      study on 62 pregnancies.
AB  - We conducted a prospective study in order to determine planned pregnancy outcome
      in systemic lupus erythematosus followed in a tertiary referral centre. Pregnancy
      was authorized if disease was inactive on 20 mg/day prednisone or less for at
      least 1 yr. Upon the diagnosis of pregnancy, systematic corticosteroids
      consisting of 10 mg/day prednisone or more were started. In the case of
      antiphospholipid antibodies, 100 mg/day aspirin was added, replaced by heparin in
      the pre-partum period. In the case of antiphospholipid syndrome complicated by
      previous thrombotic events or fetal losses despite aspirin, heparin was
      prescribed. One woman with a history of atrioventricular block was treated with
      dexamethasone. Patients were monitored by medical and obstetrical examination,
      and laboratory tests carried out at least monthly and a quarterly echography.
      Among 62 pregnancies in 38 women, lupus flare was observed in 27% of the cases,
      6% of which occurred in the post-partum period. Flares were moderate except in
      one renal involvement in a woman with prior diffuse proliferative
      glomerulonephritis. Therapy was not modified in half of the cases. Pregnancy
      ended in early spontaneous abortion not related to lupus flare (n = 10),
      stillbirth (n = 2). induced abortion (n = 2), preterm birth (n = 29) and full
      term birth (n = 19). Caesarean section was performed in nine cases. A severe
      infection occurred in two premature neonates. Another premature neonate was
      growth retarded. Two children had cutaneous neonatal lupus. No child died,
      neither had atrioventricular block. Stillbirth and severe prematurity were more
      common in mothers with antiphospholipid syndrome. After exclusion of early
      spontaneous and induced abortions, the live birth rate was 96%, that is close to
      the French general population. The main problem remains a high rate of
      prematurity, but without maternal or neonatal death.

PMID- 9255113
TI  - Ankylosing spondylitis and secretor status: a re-evaluation.
AB  - Non-secretion of ABO blood group substances in body fluids is associated with
      susceptibility to some bacterial infections. Non-secretors were previously found
      to be over-represented in patients with ankylosing spondylitis (AS) (49%)
      compared to controls (27%). Re-evaluation of secretor status in a population of
      92 AS patients and 103 controls revealed identical proportions of non-secretors
      (28%). Of 43 patients studied in both surveys, 6/22 typed initially as non
      secretors proved to be secretors using both haemagglutination inhibition assay
      (HAI) and enzyme-linked immunosorbent assay (ELISA) techniques. Loss of secreted
      blood group antigens in the saliva is the cause of this mis-typing. Careful
      attention to the method of collection, handling and preservation of saliva
      specimens is essential for accurate assessment of secretor status. Therefore,
      there is no link between secretor status and AS.

PMID- 9255114
TI  - A comparison of the prevalence of rheumatoid arthritis and other rheumatic
      diseases amongst Pakistanis living in England and Pakistan.
AB  - The impact of environmental factors on the causation of rheumatoid arthritis (RA)
      is thought to be considerable. We explored this by comparing the prevalence of RA
      amongst Pakistanis living in England, where it is relatively high amongst ethnic
      English, and in Pakistan. The frequency of other rheumatic diseases was also
      compared. Information on 2056 adult Pakistanis in England and 4232 in Pakistan
      was obtained by house-to-house surveys using identical protocols. Positive
      respondents were examined by the same two clinicians in both countries. Rheumatic
      complaints increased with age and were more common in females in both
      communities. The standardized morbidity ratio (SMR) (95% CI) of RA in England was
      2.1 (1.1-3.1) compared with Pakistan, a difference that was entirely attributable
      to females. The SMR (95% CI) for women was 3.0 (0.4-5.6) and for men 0.86 (-0.84
      to 2.56). In Pakistan, there was a trend to more reporting of some but not all
      rheumatic complaints amongst the affluent segment of the population. This was
      increasingly apparent amongst those resident in England and the possibility of an
      impact of easier ascertainment amongst the more educated cannot be discounted.
      Low back pain was significantly more common in England. Furthermore, the colder
      climate was frequently invoked as a cause of more symptoms in England. Thus,
      several factors may have influenced the observation that RA is more common
      amongst Pakistanis in England compared with Pakistan. An environmental factor
      cannot be excluded. However, the frequency of non-specific musculoskeletal pain
      was similar. The regions of Pakistan from which the two populations were derived
      were also different and immunogenetic heterogeneity might also have contributed
      to the difference in RA prevalence.

PMID- 9255115
TI  - Measurement of the quality of life in rheumatic disorders using the EuroQol.
AB  - The EuroQol is a validated quality of life (QOL) scale that has been used in
      population and clinical studies, and has been reported in patients with
      rheumatoid arthritis (RA). It is short, simple to complete, and might be suitable
      for surveys of rheumatic disease patients. The properties of this instrument were
      investigated in a postal survey of 1372 rheumatic disease patients, including 537
      with RA, 319 with osteoarthritis (OA) and 516 with fibromyalgia. In addition,
      simultaneous measurements of functional disability, pain, psychological status,
      global severity and demographic characteristics were made. EuroQol scores (0.57)
      were significantly lower than VAS health state scores (0.67) and arthritis
      related global severity scores (0.62). QOL was similar in RA and OA, but lower in
      fibromyalgia, across all instruments. The distribution of EuroQol scores had many
      gaps and was not continuous. EuroQol did not reflect VAS QOL scores at EuroQol
      levels below 0.5, and the mean score difference between the instruments below
      that level was 0.43. Many patients with low EuroQol scores (including some with
      health states that were 'worse than death') had high VAS scores. These
      differences appear to have arisen because disability, pain and depression
      questions ask about mild or moderate problems, but not both, thereby forcing
      scale compression in the mid ranges. In addition, the 'severe' value is so
      extremely abnormal that few patients endorse it. Finally, penalty scores are
      applied to those with at least one maximally abnormal score. The scoring
      properties and distributional aspects of the EuroQol indicate substantial
      problems in its use in rheumatic disease patients.

PMID- 9255116
TI  - Systemic lupus erythematosus, thrombocytopenia, microangiopathic haemolytic
      anaemia and anti-CD36 antibodies.
AB  - Thrombocytopenia in patients with acute systemic lupus erythematosus (SLE)
      frequently presents the clinician with considerable diagnostic and therapeutic
      difficulties. In this Grand Round, we present a 48-yr-old woman with a 7 yr
      history of lupus, who presented with acute proliferative glomerulonephritis and
      nephrotic syndrome, pneumonia, profound hypocomplementaemia and a severe
      microangiopathic haemolytic anaemia with associated thrombocytopenia. Her
      thrombocytopenia proved initially refractory to conventional immunosuppressive
      therapy, and corticosteroids, and resolved only with plasma exchange and repeated
      fresh frozen plasma infusions. Serological testing revealed high-titre
      antinuclear antibodies (ANA) and markedly raised antibodies to double-stranded
      (ds) DNA, but no significant elevation in anticardiolipin antibodies. Platelet
      associated IgG and IgM and antibodies to the CD36 glycoprotein antigen, expressed
      on platelets and endothelium, were detected in the serum. We address some of the
      difficult diagnostic and management issues raised by this complex patient and the
      possible immunopathological links between antibodies to CD36, immune-mediated red
      cell destruction, thrombocytopenia and thrombotic microangiopathic haemolytic
      anaemia.

PMID- 9255118
TI  - Letter from Lebanon.

PMID- 9255117
TI  - Antimalarial drugs in the treatment of rheumatological diseases.

PMID- 9255119
TI  - The use of cyclosporin A microemulsion in rheumatoid arthritis: conclusions of an
      international review.

PMID- 9255120
TI  - Inadvertent intra-articular injection of the wrong substance.

PMID- 9255121
TI  - Scalp necrosis in giant cell arteritis and review of the literature.
AB  - A patient with giant cell arteritis (GCA) who developed scalp necrosis (SN) is
      described and 23 other cases in the English language literature are reviewed. SN
      is rare and occurs in older patients of mean age 77 yr. Thirteen patients
      presented to dermatologists. Nineteen (79%) had other serious complications of
      GCA: visual loss in 16, gangrene of the tongue in four and nasal septum necrosis
      in one. The mean interval between the onset of symptoms of GCA and SN was 3.0
      months in the 19 cases which antedated corticosteroid therapy. SN resulted from
      active arteritis and no case was definitely linked to temporal artery biopsy.
      Scalp healing was complete or progressing satisfactorily in 18 cases (75%). SN is
      a potentially reversible complication of GCA and adequate corticosteroid therapy
      is mandatory. In the current case. SN related to inadequate dosage of
      prednisolone.

PMID- 9255122
TI  - Safety of meloxicam: a global analysis of clinical trials [British Journal of
      Rheumatology, 1996;35(suppl. 1):68-77].

PMID- 9255123
TI  - Middle colic artery rupture: an unusual presentation of polyarteritis nodosa.

PMID- 9255124
TI  - Distinctive ethnic differences in the incidence of osteoarthritis.

PMID- 9255125
TI  - Clinical improvement and radiological deterioration in rheumatoid arthritis.

PMID- 9255126
TI  - Joint inflammation and erosion: different mechanisms?

PMID- 9255127
TI  - Systemic lupus erythematosus following Escherichia coli sepsis in an elderly
      woman.

PMID- 9255128
TI  - Visual loss and giant cell arteritis.

PMID- 9255129
TI  - The neurologic examination.
AB  - The essentials of the neurological examination are reviewed from the perspective
      of the emergency medicine practitioner. Important historical information to be
      obtained, as well as indications and techniques for individual components of the
      physical examination, are covered. Appropriate and concise methods for
      documenting the results of the neurological examination in the patient record are
      also discussed.

PMID- 9255130
TI  - Neuroimaging.
AB  - Nonenhanced CT scan remains the most valuable and available neuroimaging study
      available in the ED. Nonenhanced CT scans are excellent for identifying acute
      hemorrhage, mass lesions, hydrocephalus, and cerebral edema. It is of limited
      value in identifying old blood, small abscesses and tumors, arteriovenous
      malformations, and aneurysms; in these cases, either enhancement of the CT or MR
      imaging may be preferable. The role of MR imaging is evolving and is becoming a
      neuroimaging modality more easily available to the emergency physician. When
      available, it is the preferred neuroimaging study for ischemic infarcts, lacunar
      infarcts, and encephalitis.

PMID- 9255131
TI  - Central nervous system resuscitation.
AB  - Traumatic injury to the central nervous system induces delayed neuronal death,
      which may be mediated by acute and chronic neurochemical changes. Experimental
      identification of these injury mechanisms and elucidation of the neurochemical
      cascade following trauma may provide enhanced opportunities for treatment with
      novel neuroprotective strategies.

PMID- 9255132
TI  - Stroke syndromes.
AB  - Emergency physicians must stay cognizant of the rapid and dramatic changes
      underway in the management of patients with acute stroke syndrome. The future
      clearly points towards a time when emergency physicians will be called upon to
      treat "brain attacks" in a manner similar to heart attacks, with early
      recognition and treatment. As effective interventions are developed, we will be
      able to alter the course, increase the survival, and decrease the morbidity and
      long-term disability of stroke patients.

PMID- 9255133
TI  - Mild head trauma.
AB  - Patients with mild traumatic brain injury constitute the overwhelming majority of
      head-injured patients seen in the emergency department. The indications for
      radiologic imaging in these patients are still undergoing study and revision. The
      Glasgow Coma Scale is a widely used triage score for head injury, but is less
      useful at identifying which patients with mild head injuries have intracranial
      pathology. There have been several retrospective studies and a few prospective
      studies examining the indications for imaging in mild to moderate head trauma.
      They all show that it is not easy to predict which patients will have CT
      abnormalities, and that some of these patients do go on to require neurosurgery.
      No set of clinical predictors have yet been put together that is capable of
      identifying all patients who are safe to be discharged without a CT scan.
      Pharmacologic therapy to help reduce axonal damage after head trauma and thus
      minimize the postconcussive sequelae of mild traumatic brain injury remains a
      challenge for physicians and neurobiologists into the next century.

PMID- 9255134
TI  - The management of severe traumatic brain injury.
AB  - An approach to the initial evaluation, resuscitation, and treatment of the
      patient with severe traumatic brain injury is presented in terms of the
      underlying physiology and literature support. The primary importance of rapid and
      complete systemic resuscitation in terms of the "ABCs" is stressed, with the goal
      of optimizing cerebral perfusion and preventing secondary insults to the injured
      brain. The integration of brain-specific treatments and diagnostic maneuvers into
      resuscitation protocols is discussed, including the role of mannitol and
      hyperventilation as well as the prioritization of CT imaging of the brain.

PMID- 9255135
TI  - Approach to generalized weakness and peripheral neuromuscular disease.
AB  - A large number of intellectually engaging and potentially serious neuromuscular
      diseases have been presented. The emergency medicine physician must be able to
      recognize those entities that have the potential to clinically deterioration. The
      evaluation of weakness requires a comprehensive, broad-based differential that is
      driven by the history and physical. Diagnostic testing is determined by the
      clinical suspicion as is the urgency for further work-up. The following are the
      final diagnoses of the eight illustrative cases that were presented at the
      beginning of this article. Case 1. This unfortunate woman had a metabolic
      myopathy that was only diagnosed after enzymatic analysis of a muscle biopsy. Her
      genetic defect, carnitine palmitoyltransferase deficiency, is unusual as it does
      not present until late in adolescence or slightly later in life. It is a defect
      in lipid metabolism in which long-chain fatty acids are unable to gain entrance
      into the mitochondrion for oxidative degradation. The defect is apparent only
      after prolonged exercise or fasting. In this patient, rhabddomyolysis led to
      acute renal failure that resolved without requiring temporary dialysis. Case 2.
      This patient had an elevated CPK-MM. Her EMG showed myopathic changes and her
      nerve conduction studies were normal. She had a positive test for antinuclear
      antibodies. A biopsy of her quadriceps muscle revealed lymphocytic infiltration
      of the muscle fibers that showed some focal myocyte degeneration. The diagnosis
      of dermatomyositis was made based on the findings noted previously and the
      heliotrope hue of her periorbital skin. A search for an occult neoplasm was
      negative. She responded moderately to a course of high-dose prednisone. Case 3.
      The laboratory test that confirmed this diagnosis was the potassium of 2.4 mEq/L.
      The remainder of the electrolytes were normal. Infusion of 20 mEq of potassium
      over 2 hours led to a prompt return of normal muscle strength. The final
      diagnosis was hypokalemic periodic paralysis. In this disease there is an
      inherited defect in the ability of the myocyte to maintain a normal transmembrane
      potential. The defect is latent until there is a precipitating factor, such as an
      high carbohydrate meal or prolonged immobility. There is also a form seen with
      thyrotoxicosis and is essentially cured when the patient becomes euthyroid. The
      disease is seen most frequently in Asian males, although it is reported in most
      ethnic groups. Prophylaxis in these patients is with acetazolamide which raises
      the serum potassium indirectly by causing a metabolic acidosis. Triamterene and
      spironolactone have also been successfully used on occasion. This patient turned
      out to have thyrotoxicosis as well. Case 4. This man had both cranial motor and
      peripheral muscular dysfunction. There was no evidence of nonmotor cranial nerve
      dysfunction, nor was there evidence of any peripheral sensory deficits. The
      diagnosis of myasthenia gravis was established by the rapid and transient
      response of this patient to 2 mg of edrophonium. He was found to have
      antiacetylcholine receptor antibodies and was also thyrotoxic. He had a stormy
      course requiring intubation and prolonged ventilation. Eventually, he underwent
      thymectomy and is stable on pyridostigmine. Case 5. Initially suspected to be
      hysteria, this patient and his relatives had botulism from home-canned peppers.
      The index case required prolonged intubation and ventilation. The patients were
      treated with polyvalent antiserum and gastric lavage to remove the residual
      contaminated food which was still in their stomachs due to the gastric atony seen
      with this disease. The botulinus toxin prevents the release of acetylcholine
      molecules from their storage vesicles in nerve terminals. Thus, this disease is
      the opposite of the cholinergic syndrome seen with organophosphate insecticide
      poisonings except that cognitive functioning is not impaired in botulism. Case 6.
      This is a celebrated case that took a great deal of sleuthing

PMID- 9255136
TI  - Pediatric migraine.
AB  - Migraine headaches are relatively common, affecting approximately 5% of all
      children. Although the differential diagnosis is extensive, a complete history
      and physical will usually lead to the correct diagnosis without laboratory or
      radiologic studies for most children. In cases of migraine complicated by
      neurologic problems, such as hemiplegia or ophthalmoplegia, neuroradiologic
      studies may be helpful to establish the diagnosis of complicated migraine.
      Treatment of migraine in children consists primarily of avoidance of triggers,
      rest, and simple analgesics. Behavior therapy, including relaxation-response
      training, has been shown to be an effective adjunct in managing both the
      frequency and intensity of the migraine attack. Use of pharmacologic agents for
      abortive and prophylactic therapy has not been extensively supported by well
      designed, well-controlled research. In general, use of these agents should be
      restricted to the small group of children with frequent, severe attacks.
      Sumatriptan, a 5-HT1 receptor agonist, has shown promise in adult patients but
      future gains in treatment will be achieved only after a better understanding of
      the cause and pathogenesis of migraine.

PMID- 9255137
TI  - Spells. Differential diagnosis and management strategies.
AB  - In summary, when approaching the patient who has had a spell of unknown cause,
      the most important differentiation to make is between a syncopal episode and a
      seizure. The history and physical examination will provide the diagnosis in
      approximately 85% of cases. Once the physician has some idea of which path to
      pursue, it is important to order the tests in a directed fashion tailored to the
      patient's presentation. A shotgun approach is neither warranted nor beneficial
      and is best avoided when possible. Some patients will remain without a diagnosis
      despite a complete workup, thus it is important for the emergency physician to
      rule out the life-threatening possibilities and to arrange the appropriate long
      term follow-up for the patient with their primary care provider.

PMID- 9255138
TI  - Diplopia in the emergency department.
AB  - Normal binocular vision requires that all involved structures; ocular, muscular,
      and neuronal; be intact and all of the intricate processes controlling conjugate
      gaze and cortical fusion be functioning. Diplopia may represent pathology at any
      point in this complex system. A careful history and physical examination may
      reveal a relatively benign etiology or may compel rapid diagnostic studies to
      evaluate the patient for neurological catastrophe.

PMID- 9255139
TI  - The serotonin syndrome.
AB  - The serotonin syndrome is characterized by mental status changes and a variety of
      autonomic and neuromuscular manifestations. Its duration is usually brief,
      resolving within hours provided that the inciting agent has been discontinued. In
      most cases, two or more types of medications known to increase the activity of
      serotonin at the 5-HT1A receptor are required to produce it, and it frequently
      begins soon after the initiation of a new treatment regimen. Treatment is largely
      supportive although limited clinical experience warrants the cautious use of
      specified agents. Although its overall incidence is unknown, it is probably low,
      and an appropriate level of suspicion coupled with an adequate knowledge of the
      patient's drug history remains the mainstay of diagnosis and treatment.

PMID- 9255140
TI  - Carotid and vertebral artery dissections.
AB  - Dissections of the carotid and vertebral arteries are a common cause of stroke in
      young adults. The diagnosis may be missed because the typical signs and symptoms
      are often delayed in onset, or easily confused with other more commonly
      encountered entities. Dissections of the carotid and vertebral arteries may occur
      spontaneously or may accompany mild to severe trauma. They present with a variety
      of findings including headache, neck and face pain, Horner's syndrome, or stroke.

PMID- 9255141
TI  - Spinal cord syndromes.
AB  - In summary, a working knowledge of the spinal cord's anatomy is critical in
      understanding the various presentations of the spinal cord syndromes. A careful
      history and physical, including a systematic neurologic examination, will direct
      the diagnostic work-up. There are a number of disorders that may affect the spine
      which are slowly progressive and do not necessarily require an emergent
      evaluation. However, patients with spinal cord trauma and spinal cord metastatic
      lesions are at risk for rapid and progressive deterioration. These patients
      require high priorization in care because morbidity and mortality may be
      significantly impacted by rapid diagnosis and initiation of therapeutic
      interventions.

PMID- 9255142
TI  - Brain death.
AB  - The development and evolution of the concept of brain death has been necessary
      due to our technologic advances in medical care and organ transplantation. The
      current operational definition of brain death is based on coma, absent brain stem
      reflexes, and apnea, with use of confirmatory testing only as necessary. This
      definition has demonstrated functional utility and may be further refined over
      time. Medical providers and the public continue to become increasingly
      comfortable with the concept of brain death.

PMID- 9255143
TI  - Molecular nuclear medicine: the best kept secret in medicine.

PMID- 9255144
TI  - Quantitation of biochemical markers of bone resorption following strontium-89
      chloride therapy for metastatic prostatic carcinoma.
AB  - The urinary production of pyridinium collagen cross-links, pyridinoline (PYD) and
      deoxypyridinoline (DPD), has been correlated to increased bone resorption in
      patients with neoplasms. This study investigated the production of these
      compounds in patients with metastatic prostate carcinoma who received palliative
      treatment that did and did not include 89Sr-chloride therapy. METHODS: Urinary
      production of PYD and DPD was measured by high-performance liquid chromatography
      and natural flucrescence detection methods. The urine from several age-matched
      groups of patients was examined for these compounds including healthy controls (n
      = 20), patients with early-stage (Stage A-B) prostate carcinoma (n = 8), patients
      with metastatic prostate carcinoma treated with conventional analgesic and
      radiotherapeutic palliation (n = 20), patients with metastatic disease who
      underwent 89Sr-chloride therapy (n = 20) and patients with mild Paget's disease
      (n = 5). Patients were also monitored for urinary PYD and DPD production for a 6
      mo interval after a palliative intervention. RESULTS: Elevated PYD and DPD (p <
      0.05) concentrations were measured in patients with metastatic and nonmetastatic
      prostate cancer and Paget's disease. The urinary production of these compounds
      remained unchanged for 6 mo after 89Sr-chloride therapy for symptomatic osseous
      metastases. However, the patients who did not undergo 89Sr-chloride therapy
      exhibited a two-fold increase in PYD and a four-fold increase in DPD above
      controls during the interval. CONCLUSION: PYD and DPD are sensitive and specific
      bone resorption markers which demonstrate a slowing of bone resorption after
      palliative 89Sr-chloride therapy in patients with bone metastases.

PMID- 9255145
TI  - Radioimmunotherapy for breast cancer using indium-111/yttrium-90 BrE-3: results
      of a phase I clinical trial.
AB  - BrE-3 is a murine IgG1 monoclonal antibody that binds to 97% of human ductal
      breast cancer specimens. A previous study documented the ability of 111In-labeled
      1,4-methyl-benzyl isothiocyanate diethylenetriamine pentaacetic acid (111In-MX
      DTPA) BrE-3 to specifically target breast cancer tissue in patients, and the
      dosimetry derived from the pharmacokinetics suggested that a useful therapeutic
      index could be obtained with 90Y-MX-DTPA BrE-3. A Phase I maximum tolerated dose
      study was, therefore, initiated. METHODS: Six patients received 111In/90Y-MX-DTPA
      BrE-3, three of them receiving 6.25 and the other three receiving 9.25 mCi/m2 of
      90Y. Pharmacokinetics, dosimetry, human anti-mouse antibody (HAMA), toxicity and
      clinical responses were evaluated. RESULTS: Three of six patients demonstrated a
      minor and transient, but objective tumor response, and none of the patients had
      significant toxicity. Tumor dosimetry ranged from 39 to 167 rad/mCi of 90Y (442
      1887 rad/ dose). HAMA response occurred in five of six patients. CONCLUSION:
      Minimal toxicity, dosimetric calculations and clinical assessment indicate that a
      useful therapeutic index can be achieved with this therapy. Indium-111/yttrium-90
      MX-DTPA BrE-3 can be safely administered to patients with metastatic breast
      cancer, and therapy doses yielded pharmacokinetics similar to those of tracer
      doses. Clinical responses, albeit transient, were achieved with single-dose
      therapy. Rapid onset of the HAMA response will hinder multicycle therapy, unless
      it is prevented with immunosuppressive drugs or the use of a "humanized"
      antibody. Further studies are needed to determine the optimal use of BrE-3 for
      radioimmunotherapy.

PMID- 9255146
TI  - Breast imaging with fluorine-18-FDG PET: quantitative image analysis.
AB  - This study evaluated various quantitative criteria for analysis of breast imaging
      with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG).
      METHODS: In a prospective study, 73 patients with abnormal mammography or
      palpable breast masses scheduled for biopsy were investigated with PET. A total
      of 97 breast tumors were evaluated by histology, including 46 benign and 51
      malignant tumors. Using a whole-body PET scanner, attenuation-corrected images
      were acquired between 40 and 60 min after tracer injection. For Patlak analysis,
      dynamic data acquisition was obtained in 24 patients. To differentiate between
      benign and malignant breast tumors, receiver operating characteristic curves were
      calculated using incrementally increasing threshold values for tumor/ nontumor
      ratios based on average and maximum activity values per region of interest,
      standardized uptake values (corrected for partial volume effect, normalized to
      blood glucose, partial volume effect and blood glucose, using the lean body mass
      as well as the body surface area) and calculating the FDG influx rate (K)
      assessed by Patlak analysis. RESULTS: Quantification of FDG uptake in breast
      tumors provided objective criteria for differentiation between benign and
      malignant tissue with similar diagnostic accuracy as compared with visual
      analysis. Applying correction for partial volume effect and normalization by
      blood glucose yielded the highest diagnostic accuracy. CONCLUSIONS: These
      quantitative methods provided accurate evaluation of PET data for differentiating
      benign from malignant breast tumors. Quantitative assessment is recommended to
      complement visual image interpretation with the potential benefit of reduced
      interobserver variability.

PMID- 9255147
TI  - Clinical significance of hepatic visualization on iodine-131 whole-body scan in
      patients with thyroid carcinoma.
AB  - The purpose of this study was to evaluate the frequency and clinical significance
      of diffuse hepatic uptake on 131I whole-body scan in 399 patients (53 males, 348
      females) with well-differentiated adenocarcinomas of the thyroid. METHODS: Two
      hundred and ninety-one diagnostic scans were performed 2 days after the
      administration of 74-370 MBq (2-10 mCI) 131I, and 824 post-therapy scans were
      done 3-5 days after the administration of 1.11-7.4 GBq (30-200 mCI) 131I. There
      was no evidence of liver metastasis in these patients. Liver and thyroid
      visualization on each 131I scan were graded from 0-4. To evaluate the
      incorporation of radioiodine to thyroglobulin and thyroid hormones, a patient's
      serum was extracted by 80% ethanol/20% trichloroacetic acid solution and analyzed
      by silica gel thin-layer chromatography. RESULTS: Diffuse hepatic uptake (> Grade
      2) was definitely seen in 239 of 399 (59.9%) of the patients and 397 of 1115
      (35.6%) of the studies. In the diagnostic scans, 36 (12.0%) showed uptake in the
      liver. In post-therapy scans, however, the incidence of liver uptake increased
      according to increased doses of 131I (39.1% with 1.11 GBq, 61.5% with 2.775-3.7
      GBq and 71.3% with 5.55-7.4 GBq). The more that uptake appeared in the residual
      thyroid, the more it appeared in the liver. There were 13 patients whose scans
      showed metastatic and liver uptake without any thyroid uptake. Fifteen patients
      showed diffuse liver uptake without uptake by the thyroid or metastasis. Follow
      up studies of seven of these patients revealed metastatic lesions. Liver uptake
      on scan related to the fraction of 131I-labeled thyroglobulin in the serum.
      CONCLUSION: Diffuse liver uptake indicated functioning thyroid remnant or
      metastasis. In a few cases, liver uptake without uptake by the thyroid or
      metastasis on whole-body scans suggests hidden metastases.

PMID- 9255148
TI  - Staging recurrent metastatic colorectal carcinoma with PET.
AB  - Accurate detection of recurrent colorectal carcinoma remains a diagnostic
      challenge. The purposes of this study were to assess the accuracy of 18FDG-PET in
      patients with recurrent colorectal carcinoma in detecting liver metastases
      compared with computed tomography (CT) and CT portography, detecting extrahepatic
      metastases compared with CT and evaluating the impact on patient management.
      METHODS: Fifty-two patients previously treated for colorectal carcinoma presented
      on 61 occasions with suspected recurrence and underwent 18FDG-PET of the entire
      body. PET, CT and CT portography images were analyzed visually. The final
      diagnosis was obtained by pathology (n = 44) or clinical and radiological follow
      up (n = 17). The impact on management was reviewed retrospectively. RESULTS: A
      total of 166 suspicious lesions were identified. Of the 127 intrahepatic lesions,
      104 were malignant, and of the 39 extrahepatic lesions, 34 were malignant.
      Fluorine-18-fluorodeoxyglucose imaging was more accurate (92%) than CT and CT
      portography (78% and 80%, respectively) in detecting liver metastases and more
      accurate than CT for extrahepatic metastases (92% and 71%, respectively).
      Fluorine-18-fluorodeoxyglucose detected unsuspected metastases in 17 patients and
      altered surgical management in 28% of patients. CONCLUSION: These data identify
      that 18FDG-PET is the most accurate noninvasive method for staging patients with
      recurrent metastatic colorectal carcinoma and plays an important role in
      management decisions in this setting.

PMID- 9255149
TI  - Arteriovenous shunts in patients with hepatic tumors.
AB  - The study aimed to investigate the influence of tumor type, tumor size, tumor
      vascularity and treatment on arteriovenous shunts between the liver and lungs in
      patients with hepatic cancer. METHODS: Our previous assessment of the degrees of
      lung shunting using intra-arterial 99mTc-macroaggregated albumin in 125 patients
      with hepatocellular carcinoma (HCC) was extended to include 377 patients with HCC
      and 25 patients with colorectal liver metastases. Patients were given 111 MBq (3
      mCi) of 99mTc-macroaggregated albumin during hepatic angiography. The lungs and
      the liver were localized as regions of interest on the digitized gamma
      scintigraphic image. The total counts taken over the lungs divided by the total
      counts taken over both the lungs and the liver gave the percentage of lung
      shunting. Tumor size was measured by computerized tomography or ultrasound scan.
      Tumor vascularity was assessed based on the degree of neovascularization. Linear
      regression and Wilcoxon rank test were used for statistical analysis. RESULTS:
      Patients with HCC had a higher median (7.6%) and a wider range (< 1-75.4%) of
      percentages of lung shunting when compared with those with colorectal liver
      metastases (median, 4.7%; range, < 1-23.9%). The lung shunting correlated with
      the tumor size in the 377 patients with HCC (r = 0.359; p < 0.0001). Excluding
      one outlier, we found a similar correlation in 24 patients with colorectal
      metastases (r = 0.686; p < 0.0001). In HCC, the mean lung shunting increased with
      increasing tumor size, up to 15 cm, and then remained almost unchanged, up to a
      size of > 20 cm. The mean lung shunting also increased with increasing
      vascularity grades, as assessed by hepatic angiography. The difference between
      any two vascularity grades was statistically significant (p = 0.0001-0.0148).
      Similar analysis by subgroups in colorectal liver metastases was impossible
      because of the small number of patients. Lung shunting decreased in HCC patients
      after the tumors were treated, but it might increase or decrease when the disease
      recurs. CONCLUSION: The lung shunting was influenced by the type, size and
      vascularity of the hepatic tumor. The change in lung shunting with the status of
      the tumor after treatment further suggests a neoplastic nature of the blood
      vessels involved in the arteriovenous shunt.

PMID- 9255150
TI  - Incrustation and uptake of skeletal imaging agent in transitional cell carcinoma.
AB  - We present a case of transitional cell carcinoma of the bladder visualized by
      99mTc-HMDP bone scintigraphy and suggest possible uptake mechanisms. Pelvic CT
      demonstrated a sessile bladder tumor with punctate and curvilinear calcifications
      on the surface areas (incrustation). Technetium-99m-HMDP bone scintigraphy
      demonstrated intense uptake corresponding to the site of the bladder tumor.
      Chemisorption of urinary 99mTc-HMDP, rather than of blood-born 99mTc-HMDP, may
      have occurred at the tumor surface.

PMID- 9255151
TI  - Technetium-99m-MIBI versus fluorine-18-FDG in diffuse multiple myeloma.
AB  - Experience of scintigraphic detection of bone lesion and active bone marrow
      involvement of multiple myeloma, especially with sestamibi and FDG-PET scans is
      in evolution. We report a case of intense sestamibi uptake in bone marrow
      correlating with the extent of the disease, while FDG-PET scans showed activity
      only in areas of active disease progression associated with pain. Technetium-99m
      sestamibi appears to indicate the extent of the disease, while [18F]FDG-PET scans
      show sites of active tumor proliferation and may be useful in directing local
      therapy such as radiation.

PMID- 9255152
TI  - FDG-PET appearance of pelvic Castleman's disease.
AB  - We report a case of Castleman's disease demonstrating 18F-fluorodeoxyglucose
      (FDG) localization by whole-body PET imaging in a pelvic soft-tissue mass shown
      on abdominopelvic CT. In this case, there is mild FDG localization within pelvic
      Castleman's disease with standard uptake values lower than in many cases of low
      grade and intermediate-grade lymphomas previously reported. FDG-PET may be of
      value as an imaging modality for differentiating Castleman's disease from
      lymphoma.

PMID- 9255153
TI  - Delayed positive thallium uptake in large B-cell non-Hodgkin's malignant
      lymphoma.
AB  - We report an unusual finding in an AIDS patient who presented with a large
      mediastinal mass and multiple lymphadenopathy. A sequential thallium and gallium
      scan to specify the nature of the mediastinal mass was requested. The early
      thallium images, acquired 15 min after the intravenous injection, showed no
      uptake in the mass. The delayed images 2 hr later showed intense thallium uptake.
      A gallium scan performed 48 hr later also showed intense gallium uptake in the
      mediastinal mass. Biopsy from the inguinal lymph node confirmed the presence of
      large-cell diffuse noncleaved malignant lymphoma. This case raises questions
      about the optimum time of imaging for thallium in high-grade lymphoma, whether
      delayed imaging is essential, about previous reports of low sensitivity of
      thallium in undifferentiated lymphoma and about the mechanism of thallium uptake
      in this type of tumor.

PMID- 9255154
TI  - PET 2-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during
      chemotherapy with gemcitabine.
AB  - This study was performed to investigate the effect of the new chemotherapeutic
      agent gemcitabine on glucose transport and metabolism in prostate carcinoma in
      vitro and in vivo. METHODS: After transplantation of rat prostate adenocarcinoma
      cells, dynamic PET measurements with fluorine-18-labeled 2-fluoro-2-deoxy-D
      glucose (18FDG) were performed in 15 animals before and 1 day after therapy with
      90 mg/kg of body weight (n = 8) and 180 mg/kg of body weight (n = 7) gemcitabine.
      In the second examination, the animals received a simultaneous injection of 18FDG
      and [3H]thymidine. Quantitative evaluation of the PET data was done using the
      standardized uptake value (SUV) as well as a three-compartment pharmacokinetic
      model. Furthermore, the incorporation of [3H]thymidine into the DNA was
      determined. In vitro measurements of the FDG, 3-O-methylglucose and thymidine
      uptake were performed immediately and 4 hr after a 24-hr incubation period with
      different doses of gemcitabine. RESULTS: FDG-SUV and the metabolic rate of FD 3
      utilization did not change significantly after therapy. However, the values for
      the transport rate constants K1 and K2 increased significantly. The incorporation
      of thymidine into the DNA of treated tumors showed an 80% decline as compared
      with a control group. In the cell culture experiments, a dose-dependent increase
      of FDG (up to 178%) and 3-O-methylglucose uptake (up to 305%) was demonstrated.
      The thymidine uptake showed a 96% decline in the nucleic acid fraction and an
      increase of up to 337% in the cytoplasmic fraction. CONCLUSION: The more global
      measures of FDG metabolism as SUV and metabolic rate of FDG utilization were
      unchanged after therapy, while DNA synthesis and cell viability declined.
      However, in vitro and in vivo evidence of an enhancement of glucose transport is
      presented, indicating that quantification by modelling may be superior for the
      evaluation of metabolic effects during chemotherapy.

PMID- 9255155
TI  - Localization of iodine-125-mIP-Des-Met14-bombesin (7-13)NH2 in ovarian carcinoma
      induced to express the gastrin releasing peptide receptor by adenoviral vector
      mediated gene transfer.
AB  - The gastrin releasing peptide receptor (GRPr) has a high affinity for the 14
      amino acid bombesin peptide. For this analysis, [125I]-Tyr4-bombesin was compared
      with [125I]-mIP-bombesin (a seven amino acid bombesin analog) for in vitro
      binding and internalization into tumor cells and for tumor localization in vivo.
      Also, a recombinant adenoviral vector (AdCMVGRPr) was used for gene transfer to
      induce the expression of GRPr in human ovarian cancer cells for binding and tumor
      localization with these radiolabeled peptides. METHODS: [125I]-mIP-bombesin was
      synthesized and compared with [125I]-Tyr4-bombesin in internalization assays
      using BNR-11 cells (mouse fibroblast cells stably transfected with GRPr) over a
      24-hr period. In vitro binding assays used BNR-11, and A427, HeLa and SKOV3.ip1
      human cancer cells, which were either uninfected or infected with AdCMVGRPr.
      Biodistribution studies were performed in normal BALB/c mice and in athymic nude
      mice bearing orthotopic SKOV3.ip1 ovarian cancer tumors. The SKOV3.ip1 tumors
      were induced to express GRPr with the AdCMVGRPr adenoviral vector. RESULTS:
      Internalization assays showed that [125I]-Tyr4-bombesin was rapidly internalized
      and catabolized at 37 degrees C with approximately 10% of the radioactivity
      remaining intracellularly at 4 hr, compared with approximately 30% with [125I]
      mIP-bombesin. HeLa, A427 and SKOV3.ip1 cells were all induced to express levels
      of GRPr that were higher than those seen with the positive control BNR-11 cells.
      Normal mice showed a lower level of radioactivity in both the blood and thyroid
      for [125I]-mIP-bombesin [0.26% +/- 0.10% injected dose per gram (ID/g) and 0.24%
      +/- 0.05% ID] than for [125I]-Tyr4-bombesin (3.5% +/- 1.6% ID/g and 5.2% +/- 4.4%
      ID) at 4 hr postinjection. Mice bearing intraperitoneal (i.p.) SKOV3.ip1 tumors
      and given AdCMVGRPr i.p. 5 days after tumor cell inoculation followed by [125I]
      mIP-bombesin i.p. at day 7 showed 16.5% +/- 4.8% ID/g in tumor compared with 5.9%
      +/- 3.0% ID/g with [125I]-Tyr4-bombesin at 4 hr postinjection. Tumor bearing mice
      given saline or a control adenovirus expressing the beta-galactosidase (LacZ)
      gene showed significantly lower tumor uptake values of both bombesin peptides.
      CONCLUSION: Internalization assays showed that [125I]-mIP-bombesin has favorable
      characteristics compared with [125I]-Tyr4-bombesin with regards to cellular
      internalization and retention. The results demonstrate successful in vitro and in
      vivo transduction of human tumor cells with a recombinant adenoviral vector
      expressing GRPr. Additionally, tumors transduced in vivo to express GRPr
      demonstrated significantly greater localization of [125I]-mIP-bombesin when
      compared with [125I]-Tyr4-bombesin.

PMID- 9255156
TI  - Triumph over mischance: a role for nuclear medicine in gene therapy.

PMID- 9255157
TI  - Thoracic and abdominal SPECT-CT image fusion without external markers in
      endocrine carcinomas. The Group of Thyroid Tumoral Pathology of Champagne
      Ardenne.
AB  - Superimposition of SPECT and computed tomography (CT) slices from the
      thoracoabdominal region was achieved without the use of external markers for 14
      studies in 13 patients with endocrine carcinoma. Technical feasibility and
      clinical validation of this retrospective fusion method were assessed. METHODS:
      Patients had a history of thyroid cancer or of carcinoid tumor. To detect tumor
      sites, CT scan and dual-isotope tomoscintigraphy were performed, with 99mTc
      hydroxymethylene diphosphonate for bone scintigraphy and with 111In
      pentetreotide, 131I or 131I-metaiodobenzylguanidine for tumor scintigraphy (TS).
      A superimposition method previously developed for the pelvic region was adapted
      to the nonrigid thoraco-abdominal region. CT-bone scintigraphy and CT-TS
      superimposed images were obtained. Clinical validation of the information
      obtained from the superimposed images was obtained from surgery or follow-up
      imaging studies performed after clinical evolution of the disease process.
      RESULTS: Reliable and reproducible registration was achieved in all patients. CT
      TS superimposed images produced accurate localization of abnormal TS foci.
      Accuracy was limited primarily by variable relative displacements of the
      thoracoabdominal organs. For 10 sites in 8 patients, localization and/or
      characterization obtained from CT-TS images was confirmed by a reference
      technique. Superimposition enabled the localization of tumor sites that otherwise
      could not have been suspected from CT alone and allowed the characterization of
      CT suspicious masses and the confirmation of CT positive sites. Nonspecific tumor
      TS uptake sites were also localized. CONCLUSION: With standard CT and dual
      isotope SPECT acquisitions, SPECT-CT fusion is feasible in the thoracoabdominal
      region without the use of external markers. Fused images were validated in 8
      patients for 10 sites. The use of this technique could probably improve the
      management and care of patients with endocrine carcinoma.

PMID- 9255158
TI  - D2-like dopamine receptor density in Tourette syndrome measured by PET.
AB  - Tourette syndrome (TS) is a chronic neurologic disorder characterized by the
      presence of involuntary motor and phonic tics. There is evidence that TS is
      associated with an abnormality of the dopaminergic system, involving postsynaptic
      D2 receptors. We tested the hypothesis that D2-like dopamine receptors are
      elevated in TS. METHODS: Twenty-nine adult patients with TS were studied by PET
      imaging with [11C]3-N-methylspiperone ([11C]NMSP). Two methods of data analysis
      were used. The first was a caudate-to-cerebellar ratio, measured at 45 min. The
      second method, applied in 20 subjects, was a two-PET scan procedure. Both used
      high specific activity [11C]NMSP, but the second scan was preceded by a dose of
      unlabeled haloperidol, which partially occupied the D2-like dopamine receptors.
      This was done to provide an absolute measure of receptor density (Bmax). All
      patients were compared to age- and sex-matched controls. RESULTS: Neither group
      showed significant differences from their control group in caudate-to-cerebellar
      ratio. However, the two-PET scan Bmax measurement demonstrated that 4 of the 20
      patients had significantly elevated D2-like receptors. In this group of 20
      patients, multiple linear regression analysis revealed a trend between the
      severity of vocal tics and Bmax values. This Bmax measure also revealed a
      significant (p < 0.05) association with performance on the Wisconsin Card Sorting
      Test. CONCLUSION: These findings suggest that not all patients with TS have an
      abnormality of D2-like receptors, but a subgroup of TS subjects has a significant
      D2-like dopamine receptor elevation. These findings also support the importance
      of applying a more quantitative method for Bmax determination to PET imaging
      analysis. The Bmax findings in the subgroup do not exclude an effect of
      intrasynaptic dopamine competition, but this effect may be less likely due to the
      high affinity of [11C]NMSP.

PMID- 9255159
TI  - Quantification of cerebral blood flow and partition coefficient using iodine-123
      iodoamphetamine.
AB  - The aim of this study was to develop a simple, noninvasive method for quantifying
      both regional cerebral blood flow (rCBF) and the partition coefficient (lambda)
      using N-isopropyl-p[123I]iodoamphetamine and SPECT. METHODS: By employing a two
      compartment model (influx, K1: outflux, k2), a new method was introduced that
      requires two serial SPECT scans at 30 min and 60 min, and a single arterial
      sample 5 min after tracer injection. The integral of the arterial input function
      is inferred from the sample by using the correlation obtained from 25 subjects.
      Two original mathematical functions, phi for K1 and gamma for lambda (= K1/k2),
      were obtained from the input functions of 12 subjects. The values of K1 and
      lambda are determined from the two scans and the single arterial sample by using
      these functions. The values obtained for K1 (= rCBF) and lambda were compared
      with those obtained by nonlinear least-squares fitting analysis and the 133Xe
      inhalation SPECT method. RESULTS: K1 and lambda were in good agreement with the
      values obtained by nonlinear least-squares fitting analysis (r = 0.873 in K1 and
      r = 0.825 in lambda), and rCBF values were closely correlated with those obtained
      by the 133Xe method (r = 0.843). CONCLUSION: The proposed method has three
      advantages: (a) accurate, simultaneous quantification of both rCBF and the
      partition coefficient; (b) simplicity and noninvasiveness; and (c) a relatively
      short period (approximately 70 min) for the study.

PMID- 9255160
TI  - Regional differences in technetium-99m-ECD clearance on brain SPECT in healthy
      subjects.
AB  - The aim of this study was to evaluate the in vivo stability of ECD brain SPECT.
      METHODS: Twenty normal volunteers (35.4 +/- 9.1 yr) each had six ECD scans at 30,
      60, 120, 240, 360 and 480 min postinjection. Each scan was acquired for 24 min
      using a triple-head SPECT system. Average counts per pixel were measured from
      frontal, temporal, parietal, occipital, cerebellum, basal ganglia, thalamus and
      white matter regions. ECD clearance rates were calculated by fitting regional
      time activity data to a monoexponential equation. Regional gray-to-white matter
      (G/W) and gray-to-cerebellum (G/C) ratios were calculated for each scan. Analysis
      of variance was used to compare regional ECD clearance and ratio measurements.
      RESULTS: The average ECD clearance was 4.3%/hr. There was a significant regional
      variation in the ECD clearance, being higher for occipital (6.34%/hr) but lower
      for both white matter (2.39%/hr) and thalamus (2.45%/hr). Both G/W and G/C ratios
      showed a significant regional variation with time. The overall G/W ratio was 2.13
      at 30 min and became progressively lower after 2 hr, reaching 1.78 at 8 hr. All
      regional G/W ratios declined with time except for thalamus where it remained
      constant at 2.15. The overall G/C ratio was 0.984 at 30 min but it declined after
      4 hr, reaching 0.955 at 8 hr. All regional G/C ratios declined with time except
      for thalamus where it increased progressively from 0.955 to 1.120 at 8 hr.
      CONCLUSION: ECD clears from normal brain slowly and shows a significant regional
      variation. As a result, G/W contrast begins to decrease after 2 hr and the gray
      matter activity pattern becomes significantly different after 4 hr. Therefore,
      the optimal imaging time may be between 30-120 min. However, images obtained up
      to 4 hr still maintain the initial gray-matter activity pattern.

PMID- 9255161
TI  - Fluorine-18-FPH for PET imaging of nicotinic acetylcholine receptors.
AB  - Visualization of central nicotinic acetylcholine receptors (nAChRs) with modern
      PET or SPECT imaging techniques has been hampered by the lack of a radioligand
      with suitable in vivo binding characteristics (i.e., high target-to-nontarget
      ratios and kinetics appropriate for the half-life of the tracer and imaging
      modality used). This paper describes in vivo binding, kinetics and pharmacology
      of a highly potent 18F-labeled analog of epibatidine, (+/-)-exo-2-(2-[18F]fluoro
      5-pyridyl)-7-azabicyclo[2.2.1]heptane ([18F]FPH), in the mouse brain with the
      view towards application of this tracer for PET imaging of nAChR in human brain.
      METHODS: Fluorine-18-FPH was administered intravenously to mice, and time
      activity curves were determined for several regions in the brain and other
      organs. Saturation and pharmacology of [18F]FPH binding was demonstrated in vivo
      by preinjecting unlabeled FPH or other drugs with known pharmacological action
      before [18F]FPH was injected. The effect of the drugs on [18F]FPH accumulation
      was evaluated. RESULTS: [18F]FPH was rapidly incorporated into the mouse brain;
      peak activity (2.4% of the injected dose) was measured at 5 min after intravenous
      administration, followed by washout to 1.1% injected dose (ID) at 60 min. Highest
      concentrations of 18F occurred at 15 min in areas known to contain high densities
      of nAChR ?e.g., thalamus [9.7% of injected dose per gram tissue (ID/g?] and
      superior colliculus (8.3% ID/g)]. Accumulation of the 18F tracer in hippocampus,
      striatum, hypothalamus and cortical areas was intermediate (5.0, 5.6, 4.2 and
      5.6% ID/g, respectively) and low in the cerebellum (2.8% ID/g). The distribution
      of [18F]FPH in the mouse brain matched that of other in vivo nAChR probes such as
      3H-labeled epibatidine or norchloroepibatidine, [3H](-)-nicotine and [3H]cytisine
      and that of nAChR densities determined in postmortem autoradiographic studies in
      rodents. Preinjection of blocking doses of unlabeled epibatidine, (-)-nicotine,
      lobeline and cytisine significantly inhibited [18F]FPH binding in thalamus and
      superior colliculus, but not in cerebellum, whereas drugs that interact with
      binding sites other than acetylcholine recognition sites of nAChR (e.g.,
      mecamylamine, scopolamine, N-methylspiperone and ketanserin) had no effect on
      [18F]FPH accumulation in any of the brain regions examined. CONCLUSION: Fluorine
      18-FPH labels nAChR in vivo in the mouse brain. Because of its high uptake into
      the brain and high ratios of specific-to-nonspecific binding, this radioligand
      appears to be ideally suited for PET imaging of nAChR in the mammalian brain.

PMID- 9255162
TI  - Physiologic modeling of PET data: quantitative conflict and challenge.

PMID- 9255163
TI  - Controversies arising from recent FDOPA articles.

PMID- 9255164
TI  - Nigrostriatal dopaminergic imaging with iodine-123-beta CIT-FP/SPECT and fluorine
      18-FDOPA/PET.

PMID- 9255165
TI  - Synthesis, in vivo evaluation and PET study of a carbon-11-labeled neuronal
      nitric oxide synthase (nNOS) inhibitor S-methyl-L-thiocitrulline.
AB  - Reports have implicated neuronal nitric oxide synthetase (nNOS) in the
      pathological effects of neurodegenerative diseases. S-Methyl-L-thiocitrulline
      (MTICU), a potent and selective nNOS inhibitor (Ki = 1.2 nM), was chosen as our
      initial target molecule for positron emitter labeling as a potential nNOS tracer.
      We report the synthesis, biological evaluation and primate brain images of S
      [11C]methyl-L-thiocitrulline ([I11C]MTICU). METHODS: The two-step synthesis of
      [11C]MTICU consisted of the S-alkylation of alpha-N-Boc-L-thiocitrulline t-butyl
      ester with [11C]Mel followed by TFA hydrolysis and HPLC purification. The final
      product was obtained within 50 min (yield = 9.1%-12.5%, based on [11C]Mel S.A. =
      27-680 Ci/mmol at end of synthesis). The lipophilicity of [11C]MTICU was
      determined by octanol/water partition coefficient (LogP). Blood stability of this
      tracer in vitro and in vivo was measured by HPLC analysis. Biodistribution using
      female Sprague-Dawley rats was performed, including examination of uptake in
      cerebellum and olfactory bulb (high nNOS) as well as cortex and brain stem (low
      nNOS). Carbon-11-MTICU was administered to a female baboon and brain images were
      obtained using a Siemens ECAT EXACT scanner for determination of brain regional
      uptake and blood-brain barrier permeability. RESULTS: At 30 min postinjection,
      [11C]MTICU remained 64% intact in vivo and 95% intact in vitro. Lipophilicity
      estimation gave Log p = 1.08 +/- 0.08 (n = 6). The brain (0.11% ID/g)-to-blood
      (0.20% ID/g) ratio was 1:2 at 30 min postinjection. Uptake in the cerebellum was
      20% higher than in either the cortex or the brain stem (p < 0.05). Blockage using
      1 mg/kg MTICU reduced uptake in the cerebellum and the cortex by 22%, but did not
      affect the brain stem. PET imaging showed that [11C]MTICU brain uptake, corrected
      for blood volume, was stable from 10 min to 1 hr at approximately 0.4% ID/organ.
      PET images of a baboon brain showed increased uptake in the region of the
      olfactory bulb compared to uniform biodistribution in the rest of the brain.
      CONCLUSION: The [11C]MTICU is a tracer that is potentially useful in determining
      nNOS levels in vivo.

PMID- 9255166
TI  - Outcome of hepatobiliary scanning in neonatal hepatitis syndrome.
AB  - To evaluate the diagnostic information gained from hepatobiliary scanning in
      infants, we reviewed 86 consecutive infants who were < or = 4 mo old and were
      treated for conjugated hyperbilirubinemia at the Hospital for Sick Children in
      Toronto between 1985 and 1993 and who had technetium iminodiacetic hepatobiliary
      scanning and a percutaneous liver biopsy performed in close temporal proximity.
      METHODS: Retrospective reviews of hospital charts and blinded reviews of
      hepatobiliary scans were performed. RESULTS: There were 58 male and 28 female
      infants (age range, 2-124 days; mean = 65 days). Hepatobiliary scanning failed to
      show biliary excretion into the gastrointestinal tract in 53 of 86 patients.
      Forty of these 53 had extrahepatic biliary atresia. The remaining 33 patients
      demonstrated biliary excretion into the gastrointestinal tract; 24 of 33 had
      neonatal hepatitis. Among 13 of the 53 patients who had no evidence of biliary
      excretion and who also did not have extrahepatic biliary atresia, 8 had
      idiopathic neonatal hepatitis, 4 had interlobular bile duct paucity and 1 had
      total parenteral nutrition-associated cholestasis. In this large series, no
      patient with extrahepatic biliary atresia showed bile drainage on hepatobiliary
      scanning. Fifty percent of patients with interlobular bile duct paucity but no
      extrahepatic obstruction failed to show biliary excretion of radionuclide. Twenty
      five percent of patients (8 of 32) with idiopathic neonatal hepatitis
      demonstrated no biliary excretion. Hepatocellular extraction was examined by
      semiquantitative analysis in the nondraining, nonbiliary atresia patients (12 of
      53). Four of these 12 patients demonstrated poor liver extraction. Three patients
      had idiopathic neonatal hepatitis, and one had bile duct paucity. Therefore, four
      of eight neonatal hepatitis patients had normal extraction, suggesting that poor
      versus good liver hepatocyte clearance cannot accurately identify neonatal
      hepatitis. CONCLUSION: Hepatobiliary scanning requires cautious interpretation.
      Nondraining scans may indicate severe neonatal hepatitis or the presence of
      interlobular bile duct paucity.

PMID- 9255167
TI  - The rim sign in hepatic abscess: case report and review of the literature.
AB  - We studied a previously healthy patient who presented with a 3-wk history of
      fever, flu-like symptoms and abdominal pain. METHODS: Blood cultures were
      positive for Escherichia coli. A computed tomography (CT) scan revealed a 2-cm
      low-density focus in the right hepatic lobe. A technetium-99m-mebrofenin scan
      showed a photopenic area in the right hepatic lobe surrounded by a rim of
      activity greater than the adjacent parenchymal activity. RESULTS: Gallbladder
      visualization was normal and the diagnosis of hepatic abscess was made. CT-guided
      percutaneous drainage of the lesion yielded six cc of pus, the culture of which
      grew E. coli, Prevotella and Bacteroides fragilis. Drainage and a 6-wk course of
      intravenous antibiotics were followed by clinical improvement and resolution of
      the abscess by CT. CONCLUSION: The rim sign and its possible mechanism of
      causation in hepatic abscess are discussed in this report, together with a review
      of the literature.

PMID- 9255168
TI  - Leukocyte-marrow scintigraphy in hyperostosis frontalis interna.
AB  - Hyperostosis frontalis interna is the term used to describe the thickening of the
      frontal bones of the skull. This thickening of the frontal bones is accompanied
      by an increase in the diploic space which results in an increased quantity of
      hematopoietically active marrow. Increased frontal bone uptake of labeled
      leukocytes has been reported in this condition, and the symmetric appearance of
      this activity may suggest its benign etiology. We have encountered a case of
      hyperostosis frontalis interna in which the uptake of labeled leukocytes was
      asymmetric and marrow scintigraphy confirmed that the activity seen was due to
      marrow not infection.

PMID- 9255169
TI  - Compartmental analysis of the complete dynamic scan data for scintigraphic
      determination of effective renal plasma flow.
AB  - We have developed an image-based compartmental analysis for estimating effective
      renal plasma flow (ERPF in units of milliliters per minute) from the full time
      activity curves of regions of interest (ROI) placed over the heart, kidneys and
      bladder. METHODS: Kidney or time-activity curves are corrected for physical
      attenuation using estimates of kidney depth derived from patient height and
      weight. Estimates of the calibration factors, Kp and Kb (mCl/counts/sec), for the
      plasma and bladder time-activity curves are determined by applying the following
      ROI analysis to each frame of the dynamic scan: (Kp)Pc(t) + (Kb)Bc(t) = Di -
      Rq(t), where P c(t) and Bc(t) represent the counting rates measured in ROI placed
      over the left ventricle blood pool and bladder at time t; Di is the known total
      injected dose, and Rq(t) represents the millicurie of tracer in the kidneys at
      time t. Once Kp and Kb have been determined by regression, the calibrated time
      activity curves are used to solve for the physiological parameter fERPF (min-1),
      which represents the fraction of the total body plasma cleared of mertiatide per
      min. The ERPF calculated by the product of fERPF and plasma volume, determined
      from patient weight, was compared to the ERPF as calculated by blood samples and
      the Schlegel and renal uptake plasma volume product scintigraphic techniques.
      RESULTS: Twenty-five adult patients with a wide range of ages and renal function
      were studied. The results of this image-based method for calculating ERPF
      correlated well with the values obtained from blood samples (linear regression
      slope = 1.06; y-int = -34.68 ml/min, r = 0.905) and offered a significant
      improvement over both the Schlegel and renal uptake plasma volume product
      estimates (p < 0.05). CONCLUSION: A scintigraphic estimation of ERPF without
      blood samples using time-activity data from the heart, kidneys and bladder
      acquired over the entire renogram is feasible and correlates well with more
      invasive techniques requiring blood samples.

PMID- 9255170
TI  - Single-sample methods to measure GFR with technetium-99m-DTPA.
AB  - Many single-sample methods have been suggested to simplify the methodology of
      glomerular filtration rate (GFR) measurement. The relative accuracy of these
      competing methods is still not clear for clinical practice. METHODS: Fifty-four
      GFR studies with 99mTc-DTPA were performed on 37 adult patients (serum creatinine
      0.8-10 mg/dl). Each study included a UV/P, plasma clearance method (three-sample)
      and single-sample methods. The single-sample methods used were those of
      Christensen and Groth (modified by Watson), Constable, Dakubu, Groth and Aasted,
      Jacobsson, Morgan, Russell and Tauxe. RESULTS: When the GFR > or = 30 ml/min (n =
      26), all of the single-sample methods were highly correlated with UV/P. The
      correlation of the single-sample method with the plasma clearance was higher than
      with UV/P. In this group (GFR > or = 30 ml/min), the Groth 4-hr sample method had
      the best value of both absolute difference and percent absolute difference (mean
      +/- s.e. = 11.05 +/- 2.51 ml/min and 14.08% +/- 2.43%, respectively). Most single
      sample methods do not perform well at GFR < 30 ml/min (n = 28), and none of them
      has a good correlation with UV/P or plasma clearance at this level of renal
      function. However, the Groth and Aasted's 4-hr sample method was the best
      compared with others (mean +/- s.e. = 8.43 +/- 1.30 ml/min for absolute
      difference, and 65.91% +/- 16.70% for percent absolute difference). CONCLUSION:
      Single-sample methods may not correctly predict GFR in advanced renal failure.
      Groth and Aasted's method with 4-hr plasma sample has both the lowest mean
      absolute difference and percent absolute difference in both the group with GFR >
      or = 30 ml/min and GFR < 30 ml/min. All methods perform acceptably at GFR > or =
      30 ml/min.

PMID- 9255171
TI  - MAG3 renogram deconvolution in kidney transplantation: utility of the measurement
      of initial tracer uptake.
AB  - The study of renal retention function by deconvolution analysis of renographic
      curves is useful to calculate quantitative parameters in renal studies. The aim
      of the work is to evaluate the usefulness of 99mTc-MAG3 renogram deconvolution in
      renal function monitoring of kidney graft recipients. METHODS: Forty-three kidney
      grafts and 112 renograms were studied: 41 were diagnosed as functioning graft, 35
      as acute tubular necrosis, 24 as acute rejection, 8 as obstruction and 4 as
      cyclosporin toxicity. The parameters calculated were mean transit time (MTT),
      time at 20% of renal retention function (T20) and initial uptake (IU). RESULTS:
      MTT and T20 were significantly longer in obstructives than in functioning grafts
      (p < 0.001). Initial uptake was significantly lower in acute tubular necrosis
      (ATN) and acute rejection (p < 0.001) and in obstructives (p < 0.05) than in
      functioning grafts. The joint evaluation of MTT and IU allowed to diagnose cases
      with graft function severely impaired. CONCLUSION: Initial uptake is useful in
      evaluating post-transplantation complications and in combination with MTT and T20
      reflects renal dysfunction severity.

PMID- 9255172
TI  - Evaluation of infections of the locomotor system with indium-111-labeled human
      IgG scintigraphy.
AB  - Indium-111-labeled human nonspecific immunoglobin G (111In-IgG) is one of the
      newer agents suggested for scintigraphic evaluation of infection and
      inflammation. In this study, the utility of this agent was studied in routine
      clinical practice. METHODS: A dose of 75 MBq 111In labeled to 2 mg IgG
      (MacroScint) was administered intravenously in 226 patients with 232 possible
      foci of infection or inflammation. Imaging was performed 4, 24 and 48 hr
      postinjection. The results were verified by culture, obtained either surgically
      (42%) or via puncture (19%) and long-term clinical and roentgenological follow-up
      (39%). Follow-up data were used in patients of whom the vast majority had a
      negative work-up, including negative 111In-IgG scintigraphy. RESULTS: All
      infected total hip (THA) and total knee arthroplasties, focal osteomyelitis,
      diabetic foot infections, septic arthritis and soft-tissue infections were
      detected (61 foci). Only one patient with early, low-grade spondylodiscitis was
      false negative with 111In-IgG. Since 111In-IgG scintigraphy does not discriminate
      between infectious and sterile inflammation, careful interpretation is necessary
      in cementless THA up to 1 yr after insertion, uptake only around the neck of the
      femoral component of a THA, recent fractures and pseudarthrosis, in which uptake
      may be caused by sterile inflammation and not by infection (specificity for
      inflammation 100%, specificity for infection of 77%). CONCLUSION: Indium-111-IgG
      scintigraphy is a very sensitive tool for detection of infectious bone and joint
      disease. Moreover, when uptake patterns of 111In-IgG, which are characteristic
      for sterile inflammation, are excluded, infection can be ruled out with a high
      degree of certainty.

PMID- 9255173
TI  - Imaging of the pancreas and related diseases with PET carbon-11-acetate.
AB  - The purpose of this study was to evaluate [1-11C]-acetate as a tracer for
      functional imaging of the pancreas and related diseases using position emission
      tomography (PET). METHODS: Thirty-three patients underwent 30 min of dynamic
      attenuation-corrected PET after intravenous administration of 740 MBq (20 mCi) of
      [1-11C]-acetate. RESULTS: The normal pancreas demonstrates prompt uptake of [1
      11C]-acetate and is visualized as early as 2 min post-injection, with maximal
      activity achieved by 5 min. Subsequent clearance of tracer from the pancreas is
      slow relative to adjacent organs and background, such that by 10 min post
      injection the pancreas is the most prominent organ in the imaging field of view.
      Pancreatic uptake of [1-11C]-acetate was unaffected by pancreatic endocrine
      insufficiency, but is absent in chronic pancreatitis complicated by exocrine
      insufficiency. Moderately reduced [1-11C]-acetate uptake was observed in acute
      uncomplicated pencreatitis. The level of tracer accumulation was substantially
      reduced in phlegmatous masses complicating pancreatitis and in chronic mass
      forming pancreatitis. Adenocarcinoma of the pancreas likewise demonstrated no
      significant uptake of [1-11C]-acetate. CONCLUSIONS: Accumulation of [1-11C]
      acetate by the pancreas allows rapid metabolic imaging using PET, and may be a
      useful metabolic probe for the study of pancreatic physiology and disease.

PMID- 9255174
TI  - Technetium-99m-labeled chemotactic peptides in acute infection and sterile
      inflammation.
AB  - Chemotactic peptides have been proposed as vehicles to image infection and
      inflammation. Previous studies have shown high uptake at the site of infection
      soon after injection, most likely because of specific binding to receptors on
      locally present leukocytes. To investigate this hypothesis, the in vivo behavior
      of a synthetic chemotactic peptide was compared to a control peptide of similar
      molecular weight with low receptor binding affinity. In addition, the potential
      to target to different infections and sterile inflammation was tested. METHODS:
      Twenty-four hours after induction of Escherichia coli, Staphylococcus aureus and
      zymosan abscesses, rabbits were i.v. injected with either 1 mCi of 99mTc-labeled
      formyl-methionyl-leucyl-phenylalanyl-lysine-hydrazinonicotinamid e (99mTc-fMLFK
      HYNIC) or 99mTc-labeled hydrazinonicotinamide-methionyl-leucyl-phenylalanyl-OMe
      (99mTc-HYNIC-MLFOMe, control peptide). Gamma camera images were obtained at 5 min
      and 1, 4, 8 and 20 hr postinjection. Biodistribution was determined at 20 hr
      postinjection. RESULTS: The blood clearances of 99mTc-fMLFK-HYNIC and 99mTc-HYNIC
      MLFOMe were similar. With time, 99mTc-fMLFK-HYNIC was retained in the abscess (E.
      coli), whereas the control agent 99mTc-HYNIC-MLFOMe was cleared from the abscess
      (0.049 +/- 0.011 versus 0.005 +/- 0.0003% 1D/g at 20 hr postinjection; p <
      0.0005). Abscess-to-contralateral muscle ratios of 99mTc-fMLFK-HYNIC rose to 36.8
      +/- 4.3 at 20 hr postinjection. E. coli, S. aureus and zymosan abscesses were
      clearly visualized from 4 hr postinjection onward. Abscess-to-background ratios
      increased to values varying from 4.4 +/- 0.2 (zymosan) to 7.1 +/- 0.6 (S. aureus)
      at 20 hr postinjection. The uptake in S. aureus and zymosan abscesses did not
      differ significantly from the uptake in E. coli abscesses. CONCLUSIONS: fMLFK
      HYNIC is retained in both acute infection and sterile inflammation by means of
      specific receptor binding if sufficient cellular infiltration is present.

PMID- 9255175
TI  - Localization of radiolabeled chemotactic peptide at focal sites of Escherichia
      coli infection in rabbits: evidence for a receptor-specific mechanism.
AB  - The infection imaging properties of a high-affinity 99mTc-labeled chemotactic
      peptide receptor agonist (N-formyl-methionyl-leucyl-phenylalanine-lysine; N-For
      MLFK) were compared with a low-affinity agonist (N-Acetyl-MLFK; N-Ac-MLFK), a
      moderate-affinity antagonist (N-isobutyloxycarbonyl-MLFK; N-IBoc-MLFK) and non
      specific inflammation imaging agents. METHODS: All peptides were prepared by
      solid-phase methods and purified by high-performance liquid chromatography. The
      products were assayed in vitro for N-formyl-methionyl-leucyl-phenylalanine
      receptor binding and superoxide production. Three types of studies were performed
      in rabbits with Escherichia coli infection: (Study A) Four groups of six animals
      were coinjected with 99mTc-N-For-MLFK-hydrazinonicotinamide (N-For-MLFK-HYNIC)
      plus 111In-immunoglobulin G, 111In-red blood cells or 111In-diethylene triamine
      pentaacetic acid. (Study B) Three groups of six rabbits were coinjected with
      111In-leukocytes plus 99mTc-N-For-MLFK-HYNIC, 99mTc-N-Ac-MLFK-HYNIC or 99mTc-N
      IBoc-MLFK-HYNIC. (Study C) Two groups of six rabbits were injected with 99mTc-N
      For-MLFK-HYNIC and 111In-leukocytes with and without an excess of antagonist. In
      all three studies, the radiopharmaceuticals were injected 24 hr after infection
      and dual photon (99mTc and 111In) gamma camera images were acquired at 2-3 and 16
      18 hr later. Target-to-background (T/B) ratios were calculated for regions of
      interest drawn over the infected and contralateral normal tissue. RESULTS: N-For
      MLFK, N-Ac-MLFK and N-IBoc-MLFK had EC50s for receptor binding of 2.0, 830 and
      150 nM, respectively. The corresponding EC50s for superoxide production were
      20.0, approximately 10(3) and > 10(4). Study A demonstrated that the T/B for
      99mTc-N-For-MLFK-HYNIC was higher than for any of the nonspecific imaging agents
      (p < 0.001), and 111In-immunoglobulin G had a higher T/B ratio than 111In
      diethylenetriamine pentaacetic acid (p < 0.01) or 111In-red blood cells (p = NS).
      Study B showed that 99mTc-N-For-MLFK-HYNIC had a higher T/B ratio than the other
      peptides (p < 0.001). 111In-leukocytes and 99mTc-N-IBoc-MLFK-HYNIC had comparable
      T/B ratios, which were higher than for 99mTc-N-Ac-MLFK-HYNIC (p < 0.05). Study C
      demonstrated that coinjection with an antagonist resulted in a significant
      reduction in the T/B ratio for 99mTc-N-For-MLFK-HYNIC (p < 0.001), but did not
      affect the T/B ratio for 111In-leukocytes. CONCLUSION: Nonspecific mechanisms
      contribute minimally to the localization of 99mTc-chemotactic peptide analogs at
      sites of infection and the majority of the accumulation appears to be receptor
      mediated. Also, chemotactic peptide receptor antagonists can be used for
      infection imaging. These results provide important new insights for future
      radiopharmaceutical development.

PMID- 9255176
TI  - Technetium-99m-labeled chemotactic peptides: specific for imaging infection?

PMID- 9255178
TI  - Simplified calculation of MRglc using PET.

PMID- 9255177
TI  - The physical and chemical nature of technegas.
AB  - Technegas, the discrete radio-aerosol particle, containing 99mTc has been
      investigated, and the chemical evolution and physical properties of the particle
      demonstrated. METHODS: A commercial technegas generator was used to produce
      aerosols according to standard clinical procedures. The aerosols were collected
      by electrostatic precipitation and examined with transition electron microscopy
      (TEM), scanning electron microscopy (SEM) and force microscopy. The chemical
      evolution was examined by x-ray techniques and thermogravimetric analysis.
      RESULTS: The active particle was identified as hexagonal platelets of metallic
      technetium contained within a thin layer of graphitic carbon. This composite
      structure is discussed in light of the metal particle behaving as a template for
      the carbon capsule. The average size of the observed hexagonal platelets, 30-60
      nm, was only weakly dependent on the concentration of technetium in the crucible.
      CONCLUSION: The mechanism for the formation of the technegas pancreas has been
      developed and the particles involved characterized. It appears that the use of
      other metals also leads to the formation of similar materials.

PMID- 9255179
TI  - Bias in PET quantitation due to camera calibration procedures.

PMID- 9255180
TI  - Nocturnal hypoglycemia in children with diabetes: an important problem revisited.

PMID- 9255181
TI  - Tanner-Whitehouse versus Greulich-Pyle in bone age determinations.

PMID- 9255182
TI  - Laparoscopic versus open splenectomy: how clear is the choice?

PMID- 9255183
TI  - An evolving view of hyper-IgM syndrome.

PMID- 9255184
TI  - Toddler-to-mother transmission of varicella-vaccine virus: how bad is that?

PMID- 9255185
TI  - Preoperative fasting: you don't have to be cruel to be kind.

PMID- 9255186
TI  - Annular pancreas.

PMID- 9255187
TI  - Immunobiology of childhood tuberculosis: a window on the ontogeny of cellular
      immunity.

PMID- 9255188
TI  - Nocturnal hypoglycemia in children and adolescents with insulin-dependent
      diabetes mellitus: prevalence and risk factors.
AB  - OBJECTIVES: To evaluate the prevalence and risk factors of nocturnal hypoglycemia
      (NH) in children and adolescents with insulin-dependent diabetes mellitus. STUDY
      DESIGN: A total of 150 patients, 87% of whom were receiving conventional therapy,
      were admitted to the hospital for one night. Blood glucose (BG) levels were
      measured hourly from 10 PM to 8 AM. RESULTS: The prevalence of NH was 47%; NH was
      asymptomatic in 49% of the cases. Risk factors were as follows: at least two
      episodes of severe hypoglycemia from onset of insulin-dependent diabetes mellitus
      (p = 0.0004), insulin dosage > 0.85 IU/kg per day (p = 0.02), more than 5% of BG
      measurements < or = 3.3 mmol/L during the last month of monitoring (p = 0.04).
      The risk decreased significantly with age (p = 0.0001). Both high predictive
      values and significant relative risk were found for BG thresholds < or = 5.2
      mmol/L at dinner time (p < 0.0001) and < or = 6.7 mmol/L at 7 AM (p < 0.0001).
      When BG values at 10 PM were used, prediction of NH was weak. CONCLUSIONS:
      Nocturnal hypoglycemia occurred frequently in children and adolescents with
      insulin-dependent diabetes mellitus. Our study found risk factors that will help
      pediatricians to identify those children with a high risk of NH. Especially in
      these patients, counseling based on the BG values before dinner and early in the
      morning is indicated to reduce the prevalence of NH.

PMID- 9255189
TI  - Tanner-Whitehouse bone age reference values for North American children.
AB  - On the basis of 1090 x-ray films from 225 boys and 225 girls ages 8 to 16 years
      participants in the Project Heartbeat longitudinal study who were living in a
      generally above-average income environment near Houston, Tex.-we provide Tanner
      Whitehouse Mark 2 RUS (radius, ulna, and selected metacarpals and phalanges) bone
      age reference values for North American children of European origin. We designate
      these values as US90 (for the 1990s) reference values, in contrast to the
      original British bone age standards, called UK60 (for the 1960s). The US90
      children matured considerably earlier than those on which the UK60 standards were
      based, though only about 3 months earlier than contemporary Spanish children. A
      study of 190 x-ray films from a research longitudinal series of 23 healthy boys
      in Virginia yielded values very close to the Houston values, confirming that our
      US90 reference values should be used in North America, pending a more extensive
      survey.

PMID- 9255190
TI  - Comparison of laparoscopic and open splenectomy in children with hematologic
      disorders.
AB  - OBJECTIVE: To compare laparoscopic and traditional open splenectomy in children
      with nonmalignant hematologic disorders. STUDY DESIGN: Retrospective review of 36
      consecutive nonrandomized splenectomies (16 laparoscopic and 20 open) performed
      for hematologic disorders at a single pediatric institution during the past 3
      years. The two-sided Mann-Whitney U test for non-parametric variables was used
      for statistical analysis. RESULTS: An open procedure was performed on 20 patients
      (mean age, 9.7 years), five of whom had a concomitant cholecystectomy. A
      laparoscopic splenectomy was performed on 16 children (mean age, 10.3 years),
      seven of whom had a concomitant cholecystectomy. The mean anesthesia and
      operative times were longer in the laparoscopic than in the open group (p <
      0.001). However, the mean number of hours of postoperative analgesia was less in
      the laparoscopic group (p < 0.005). Patients who had laparoscopic splenectomy
      were also discharged home earlier (p < 0.01) and resumed a regular diet sooner.
      Mean operating room charges were higher in the laparoscopic group (p < 0.001),
      but total hospitalization costs were not significantly different. Postoperative
      complication rates were similar. The hematologic response was comparable.
      CONCLUSIONS: laparoscopic splenectomy is feasible and safe in children with
      hematologic disorders. Although it currently requires more operative time than
      the open approach, it is superior with regard to duration of postoperative
      analgesia, duration of hospital stay, and recovery of bowel function.

PMID- 9255191
TI  - Clinical spectrum of X-linked hyper-IgM syndrome.
AB  - We report the clinical and immunologic features and outcome in 56 patients with X
      linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand
      gene. Upper and lower respiratory tract infections (the latter frequently caused
      by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often
      associated with Cryptosporidium infection) were common. Many patients had chronic
      neutropenia associated with oral and rectal ulcers. The marked prevalence of
      infections caused by intracellular pathogens suggests some degree of impairment
      of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation
      to mitogens were normal, a defective in vitro proliferative response to antigens
      was observed in some patients, and additional defects of cell-mediated immunity
      may be presumed on the basis of current knowledge of CD40-ligand function. All
      patients received regular infusions of immunoglobulins. Four patients underwent
      liver transplantation because of sclerosing cholangitis, which relapsed in there.
      Three patients underwent bone marrow transplantation. Thirteen patients (23%)
      died of infection and/or liver disease. X-linked hyper-IgM syndrome, once
      considered a clinical variant of hypogammaglobulinemia, is a severe
      immunodeficiency with significant cellular involvement and a high mortality rate.

PMID- 9255192
TI  - Randomized, multicenter trial of inhaled nitric oxide and high-frequency
      oscillatory ventilation in severe, persistent pulmonary hypertension of the
      newborn.
AB  - BACKGROUND: Although inhaled nitric oxide (iNO) causes selective pulmonary
      vasodilation and improves oxygenation in newborn infants with persistent
      pulmonary hypertension, its effects are variable. We hypothesized (1) that the
      response to iNO therapy is dependent on the primary disease associated with
      persistent pulmonary hypertension of the newborn (PPHN) and (2) that the
      combination of high-frequency oscillatory ventilation (HFOV) with iNO would be
      efficacious in patients for whom either therapy alone had failed. METHODS: To
      determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we
      enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were
      stratified by predominant disease category: respiratory distress syndrome (n =
      70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary
      hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and
      congenital diaphragmatic hernia (n = 34); they were then randomly assigned to
      treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment
      failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in
      crossover to the alternative treatment; treatment failure after crossover led to
      combination treatment with HFOV plus iNO. Treatment response with the assigned
      therapy was defined as sustained PaO2 of 60 mm Hg or greater. RESULTS: Baseline
      oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during
      treatment with conventional ventilation. Ninety-eight patients were randomly
      assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three
      patients (26%) recovered with the initially assigned therapy without crossover
      (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival
      was 100% and there were no differences in days of mechanical ventilation, air
      leak, or supplemental oxygen requirement at 28 days. Of patients whose initial
      treatment failed, crossover treatment with the alternate therapy was successful
      in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125
      patients in whom both treatment strategies failed, 32% responded to combination
      treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either
      treatment alone or combination therapy. By disease category, response rates for
      HFOV plus iNO in the group with respiratory syndrome and the group with meconium
      aspiration syndrome were better than for HFOV alone or iNO with conventional
      ventilation (p < 0.05). Marked differences in outcomes were noted among centers
      (percent death or treatment with extracorporeal membrane oxygenation = 29% to
      75%). CONCLUSIONS: We conclude that treatment with HFOV plus iNO is often more
      successful than treatment with HFOV or iNO alone in severe PPHN. Differences in
      responses are partly related to the specific disease associated with PPHN.

PMID- 9255193
TI  - Dose response to inhaled nitric oxide in pediatric patients with pulmonary
      hypertension and acute respiratory distress syndrome.
AB  - OBJECTIVE: To determine the pulmonary vascular functional dose response to
      inhaled nitric oxide (NO) for infants and children with acute respiratory
      distress syndrome and pulmonary artery hypertension. DESIGN: Prospective,
      clinical observational study. SETTING: Thirteen-bed pediatric intensive care unit
      at a 168-bed children's hospital. PATIENTS: Infants and children requiring
      mechanical ventilation with an oxygenation index greater than 10. METHODS:
      Children with severe acute respiratory distress syndrome received inhalation
      therapy with NO after conventional mechanical ventilation failed to result in
      improvement. Inhaled NO was sequentially titrated from 10 parts per million to
      20, 40, 60, and 80 ppm at 10-minute intervals. A reduction of at least 30% in the
      pulmonary vascular resistance index (PVRI), or a reduction in mean pulmonary
      artery pressure of at least 10%, or an increase in the hypoxemia score of at
      least 20%, or a decrease in the oxygenation index of at least 20% from
      pretreatment values was considered a therapeutic response. After sequential
      titration, children who responded received continuous inhaled NO at the lowest
      dose associated with a therapeutic response. RESULTS: Fourteen children received
      15 trials with inhaled NO (median age, 63.4 months; range, 0.4 to 201 months).
      One patient's condition deteriorated during the titration phase, unrelated to NO
      treatment, and the patient was withdrawn from the study protocol. The mean (+/-
      SD) pretreatment oxygenation index was 35 +/- 15, which decreased to 32 +/- 20 at
      80 ppm of inhaled NO (p = 0.01). Ten children had pulmonary artery catheter
      measurements. The PVRI decreased by 30% or greater in seven children (70%). One
      child had a minimal decrease in PVRI during the titration phase but demonstrated
      an increase of more than 30% after NO therapy was discontinued. Mean pretreatment
      PVRI (270 +/- 106) decreased to 207 +/- 92 dynes/sec per cubic centimeter per
      square meter at 80 ppm of inhaled NO (p = 0.06). Pretreatment mean pulmonary
      artery pressure (31 +/- 7) decreased to 28 +/- 5 mm Hg at 80 ppm of inhaled NO (p
      = 0.04). Six trials (43%) showed an increase of 20% or greater in their hypoxemia
      score. Maximum improvement in the hypoxemia score and reduction in OI, PVRI, and
      mean pulmonary artery pressure occurred at 20 to 40 ppm of NO. Ten trials led to
      continuous inhaled NO therapy ranging from 7 to 661.5 hours, with a median of 47
      hours. Systemic hypotension was not observed in any patient, and the maximum
      methemoglobin level was 5%. CONCLUSION: Inhaled NO appears to be a safe, although
      variably effective, therapy for the treatment of infants and children with acute
      respiratory distress syndrome. The maximum dose response occurs between 20 and 40
      ppm of inhaled NO. Systemic side effects did not occur in any child who received
      NO therapy.

PMID- 9255194
TI  - Longitudinal follow-up of a cohort of newborn infants treated with inhaled nitric
      oxide for persistent pulmonary hypertension.
AB  - OBJECTIVE: To describe the outcome of a group of term newborn infants treated
      with inhaled nitric oxide for severe persistent pulmonary hypertension. STUDY
      DESIGN: We performed a prospective longitudinal medical and neurodevelopmental
      follow-up of 51 infants treated as neonates for persistent pulmonary hypertension
      of the newborn with inhaled nitric oxide. The original number of treated infants
      was 87, of whom 25 died in the neonatal period; of 62 infants who survived, 51
      were seen at 1 year of age and 33 completed a 2-year evaluation. Statistical
      analysis used population medians, means, and standard deviations for parameters
      assessed. Paired t tests and chi-square analysis were used to compare outcomes
      measured at 1 year with assessment at 2 years for the 32 infants seen at both 1-
      and 2-year visits. RESULTS: At 1-year follow-up median growth percentiles were
      20%, 72.5%, and 50% for weight, length, and occipitofrontal circumference,
      respectively. Thirteen of 51 infants (25.5%) were < 5th percentile in weight.
      Nine of 51 infants (17.6%) had feeding problems (need for gastrostomy feeding or
      gastroesophageal reflux), and 14 (27.5%) had a clinical diagnosis of reactive
      airways disease. Infant development as measured by the Bayley Scales of Infant
      Development was 104 +/- 16 for the mental development index and 97 +/- 20 for the
      psychomotor index. Six of 51 infants (11.8%) were found to have severe neurologic
      handicaps, defined as a Bayley score on either the mental development or
      psychomotor index of < 68, abnormal findings on neurologic examination, or both.
      Fewer children (6.1% vs 15.7%) required supplemental oxygen at 2 years compared
      with 1 year, and performance on the psychomotor index of the Bayley Scales
      improved significantly. CONCLUSIONS: One- and 2-year follow-up of a cohort of
      infants with persistent pulmonary hypertension of the newborn who were treated
      with inhaled nitric oxide had an 11.8% (1 year) and 12.1% (2-year) rate of severe
      neurodevelopmental disability. There are ongoing medical problems in these
      infants including reactive airways disease and slow growth that merit continued
      close longitudinal follow-up.

PMID- 9255195
TI  - Pharmacokinetics of once-daily dosing of gentamicin in neonates.
AB  - In a prospective, randomized trial of once-daily versus twice-daily intravenous
      or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once
      daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily
      intravenous dosing group and the twice-daily intravenous or intramuscular dosing
      group, respectively, had mean steady-state gentamicin peak concentrations of 10.7
      versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7
      versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7
      micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and
      volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic
      effects were identified in any group. Once-daily gentamicin therapy with 5.0
      mg/kg in neonates achieves peak serum levels that are more suitable for optimal
      bacterial killing than those which traditional regimens achieve. Similar trough
      levels suggest that even larger doses and longer dosing intervals may be ideal in
      term neonates.

PMID- 9255196
TI  - Potassium metabolism in extremely low birth weight infants in the first week of
      life.
AB  - OBJECTIVE: Nonoliguric hyperkalemia has been reported to occur in the first week
      of life in as many as 50% of extremely low birth weight (ELBW) infants. We
      studied potassium balance and renal function in the first 5 days of life to
      characterize potassium metabolism during the three phases of fluid and
      electrolyte homeostasis that we have described in ELBW infants and to elucidate
      the factors that contribute to the development of nonoliguric hyperkalemia. STUDY
      DESIGN: Plasma potassium concentration (PK), potassium intake and output, and
      renal clearances were obtained for the first 6 days of life in 31 infants with a
      birth weight of 1000 gm or less. Collection periods in which urine flow rate was
      greater than or equal to 3 ml/kg per hour and weight loss was greater than or
      equal to 0.8 gm/kg per hour were denoted to be diuretic. Prediuresis includes all
      collection periods before the first diuretic period; diuresis includes all
      collection periods between the first and last diuretic periods; postdiuresis
      includes all collection periods after the last diuretic period. Infants with a PK
      greater than 6.7 mmol/L on at least one measurement were denoted to have
      hyperkalemia. RESULTS: PK increased initially after birth--despite the absence of
      potassium intake- and then decreased and stabilized by the fourth day of life.
      Diuresis occurred in 27 of 31 infants. The age at which PK peaked was closely
      related to the onset of diuresis. PK decreased significantly during diuresis as
      the result of a more negative potassium balance, despite a significant increase
      in potassium intake. In fact, PK fell to less than 4 mmol/L in 13 of 27 infants
      during diuresis. After the cessation of diuresis, potassium excretion decreased
      even though there was a significant increase in potassium intake, potassium
      balance was zero, and PK stabilized. Hyperkalemia developed in 11 of 31 infants.
      The pattern of change in PK with age was similar in infants with normokalemia and
      hyperkalemia: PK initially increased (essentially in the absence of potassium
      intake) and then decreased and stabilized by the fourth day of life. However, the
      rise in PK after birth was greater in infants with hyperkalemia than in those
      with normokalemia: 0.7 +/- 0.2 versus 1.8 +/- 0.2 mmol/L (p < 0.001). No
      differences in fluid and electrolyte homeostasis or renal function were
      identified as associated with hyperkalemia. CONCLUSIONS: PK increases in most
      ELBW infants in the first few days after birth as a result of a shift of
      potassium from the intracellular to the extracellular compartment. The increase
      in the glomerular filtration rate and in the fractional excretion of sodium, with
      the onset of diuresis, facilitates potassium excretion, and PK almost invariably
      decreases. Hyperkalemia seems to be principally the result of a greater
      intracellular to extracellular potassium shift immediately after birth in some
      ELBW infants.

PMID- 9255197
TI  - Potassium intake and cardiovascular reactivity in children with risk factors for
      essential hypertension.
AB  - OBJECTIVES: Our study objectives were as follows: (1) to determine whether
      urinary excretion of potassium is lower in black than in white children, (2) to
      determine whether cardiovascular reactivity (CVR) varies inversely with dietary
      intake of potassium, and (3) to confirm that CVR is greater in black than in
      white children, and in children with a family history of hypertension than in
      those without such a history. STUDY DESIGN: Baseline measurements included 24
      hour urinary sodium, potassium, and creatinine levels and food intake (by
      questionnaire). Resting and stress blood pressure were measured during blood
      sampling, cold water foot immersion, and a video game before and after 1 week
      each of supplementation with potassium citrate, 1.5 mmol/kg per day, and placebo
      administered in random order. RESULTS: Thirty-nine children aged 7 to 15 years
      were studied. White subjects had higher baseline excretion of potassium than
      black subjects (p < 0.001) and higher vegetable intake (p < 0.01), which were
      positively correlated (r = 0.53, p < 0.001). At baseline, the 24-hour urinary
      potassium/creatinine ratio varied inversely with diastolic CVR to the video game
      stressor in white children (r = -0.55, p = 0.02). Cardiovascular reactivity was
      not attenuated measurably by potassium supplementation compared with placebo. The
      CVR was greater in children with a family history of hypertension than in those
      without, but was not greater in black children than in white children.
      CONCLUSIONS: The urinary potassium/creatinine ratio is higher in white than black
      children because their intake of vegetables is greater; dietary potassium intake
      may modulate CVR, particularly in white children with a family history of
      hypertension, but may need to be supplemented for more than 1 week to demonstrate
      attenuation of CVR; and a family history of hypertension may be a stronger
      predictor of enhanced CVR than is race.

PMID- 9255198
TI  - Neonatal manifestations of congenital dyserythropoietic anemia type I.
AB  - Congenital dyserythropoietic anemia type I is a rare inherited bone marrow
      disorder characterised by macrocytic anemia with pathognomonic morphological
      ultrastructural features in erythroid precursors. The disease is usually not
      diagnosed in the neonatal period. In a retrospective study of 31 patients we
      found that 17 were first seen in the neonatal age with significant anemia (birth
      hematocrit 0.34 +/- 0.07); 14 of the 17 infants also had early jaundice. Six
      infants were small for gestational age and two had syndactyly. Although rare,
      congenital dyserythropoietic anemia type I should be considered in the
      differential diagnosis of neonatal anemia.

PMID- 9255199
TI  - Association between liver transplantation for Langerhans cell histiocytosis,
      rejection, and development of posttransplant lymphoproliferative disease in
      children.
AB  - OBJECTIVE: Langerhans cell histiocytosis (LCH) is an unusual indication for
      orthotopic liver transplantation in children. Data from limited case reports
      suggest that orthotopic liver transplantation for LCH is associated with
      excellent survival rates and a low incidence of disease recurrence. However, in
      our experience, children who have transplantation for LCH appeared to experience
      a high incidence of refractory rejection and posttransplant lymphoproliferative
      disease (PTLD). STUDY DESIGN: Data from 398 liver transplants performed in 298
      children younger than 16 years of age were reviewed to determine the presence of
      risk factors for PTLD in patients with LCH and other causes of liver failure.
      RESULTS: The incidence of PTLD was significantly higher in children who received
      transplants for LCH compared with all indications (p < 0.001) and specific
      indications that were associated with the development of PTLD (p < 0.002). Among
      patients in whom PTLD developed, there was no significant difference in the
      incidence of primary Epstein-Barr virus infections in patients who receive
      transplantation for LCH (4/4, 100%) versus all other indications (12/14, 86%).
      Children who had transplantation for LCH were older than those who had
      transplantation for other indications (LCH median age 3.1 years, other
      indications 1 year). The incidence of rejection, especially refractory rejection,
      was greater in patients who had transplantation for LCH (100% and 50%,
      respectively) compared with those who had transplantation for other indications
      (70% and 10%, p < 0.02 for refractory rejection). CONCLUSIONS: Patients who had
      transplantation for liver disease related to LCH experienced a 67% long-term
      survival (median follow up 5.8 years, range 2.1 to 7.5 years). Recurrent LCH
      occurred in only 33% of patients and was easily managed. However, PTLD developed
      in two thirds of these patients, perhaps in part because of the high incidence of
      refractory rejection. This series therefore demonstrates an association between a
      primary disease process and the development of PTLD. Although the data indicate
      that children with LCH-induced liver failure benefit from transplantation,
      special care must be exercised in screening for and preemptive treatment of PTLD.

PMID- 9255200
TI  - Growth and growth hormone secretion in children with cancer treated with
      chemotherapy.
AB  - OBJECTIVE: To evaluate the effect of chemotherapy on growth and growth hormone
      (GH) secretion. METHODS: We analyzed growth and GH secretion in 60 children in
      complete remission after treatment by chemotherapy and surgery for malignant
      solid tumors. None of them received cranial radiotherapy. Growth hormone reserve
      was assessed by at least two stimulation tests (clonidine, L-dopa, growth hormone
      releasing hormone). In 12 children the reserve of GH pretreatment was also
      evaluated. RESULTS: Growth hormone deficiency (GHD) was observed in 27 of 60
      patients (45%). At diagnosis, mean standing height was +0.23 +/- 0.11 standard
      deviation score (SDS) in the GHD group and +0.16 +/- 0.10 SDS in the non-GHD
      group. After chemotherapy, mean standing height in the GHD group was -0.28 +/-
      0.15 SDS and -0.14 +/- 0.11 in the non-GHD group (p < 0.05), and the growth rate
      was +0.13 +/- 0.07 SDS in the GHD group and +0.22 +/- 0.18 SDS in the non-GHD
      group. For a mean follow-up of 30 months, the mean standing height was -0.46 +/-
      0.29 SDS in the GHD group and -0.24 +/- 0.16 SDS for the non-GHD group (p <
      0.05), and the growth rate was -0.27 +/- 0.19 SDS in the GHD group and -0.16 +/-
      0.12 SDS in the non-GHD group (p < 0.05). The GH response to clonidine was
      significantly less than that found with the other stimuli. There was correlation
      between the dose intensity of some drugs and the subsequent GH response to
      stimulation tests. The GHD group was found to have received significantly higher
      doses of actinomycin D than the non-GHD group (p < 0.05). Growth impairment and
      GHD were not found to be correlated with duration of treatment and follow-up,
      tumor type, sex, or age. CONCLUSIONS: Chemotherapy as the sole form of treatment
      in children with cancer interferes with growth. The observed impairment of growth
      depends, at least in part, on a GHD related to chemotherapy. The growth rate in
      conjunction with the GH response to clonidine provides a sensitive measure of GHD
      associated with chemotherapy.

PMID- 9255201
TI  - Economic evaluation of respiratory syncytial virus infection in Canadian
      children: a Pediatric Investigators Collaborative Network on Infections in Canada
      (PICNIC) study.
AB  - OBJECTIVES: To quantify the cost and distribution of health care resources
      consumed annually in management of Canadian children from birth to 4 years of age
      with respiratory syncytial virus (RSV) infection. STUDY DESIGN: Estimates of
      direct medical expenditures (in 1993 U.S. dollars) were collected from a
      prospective cohort study of hospitalized children with RSV and from national and
      provincial databases. RESULTS: The annual cost of RSV-associated illness was
      almost $18 million. The largest component of direct expenditures (62%) was for
      inpatient care for the estimated 0.7% of all infected children ill enough to
      require admission. Physician fees comprised only 4% of inpatient expenses.
      Expenditures for ambulatory patients accounted for 38% of direct costs.
      CONCLUSIONS: The greatest reductions in the economic cost of RSV infections will
      be found in interventions that reduce duration of or prevent hospital stay. Costs
      for management of RSV infection in children in the Canadian health care system
      are considerably less than charges reported in the United States.

PMID- 9255202
TI  - Safety of repeated intermittent courses of aerosolized recombinant human
      deoxyribonuclease in patients with cystic fibrosis.
AB  - OBJECTIVES: To determine the effect of repeated doses of aerosolized recombinant
      human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies,
      acute allergic reactions, and pulmonary function in patients with cystic
      fibrosis. DESIGN: A multicenter, open-label study in which 184 patients received
      10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout
      period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase
      antibodies and pulmonary functions were performed. RESULTS: Detectable anti
      rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes
      in their symptoms from the time they entered the trial. Antibodies detected were
      all of the IgG isotype. Increases in both forced expired volume in 1 second and
      forced vital capacity were noted from the beginning to the end of each cycle of
      treatment returning to baseline during the off-treatment period of each cycle.
      Seropositivity to rhDNase was not associated with allergic reactions and had no
      relationship on improvement in pulmonary function. CONCLUSIONS: Development of
      anti-rhDNase antibodies occurred in a small number of patients and was not
      associated with side effects. Intermittent administration of rhDNase for 24 weeks
      to patients with cystic fibrosis was well tolerated and was not associated with
      anaphylaxis in any patient. Pulmonary function improved significantly during the
      14-day cycles while rhDNase was administered and returned to baseline when
      rhDNase was discontinued.

PMID- 9255203
TI  - Residual neurologic sequelae after childhood cerebral malaria.
AB  - BACKGROUND: Cerebral malaria is an important cause of pediatric hospital
      admissions in the tropics. It commonly leads to neurologic sequelae, but the risk
      factors for this remain unclear and the long-term outcome unknown. OBJECTIVE: The
      purpose of this study was to identify the common forms of neurologic sequelae
      that occur after cerebral malaria, their evolution over time, and the major
      clinical risk factors for residual disability. STUDY DESIGN: Prospective study in
      624 children admitted with cerebral malaria to two hospitals in The Gambia, West
      Africa. RESULTS: We found that 23.3% of survivors had neurologic sequelae on
      discharge from the hospital. By 1 month the proportion had decreased to 8.6%, and
      at 6 months only 4.4% of survivors were found to have residual neurologic
      sequelae. The most common forms of neurologic sequelae were paresis and ataxia,
      often found in combination with other neurologic abnormalities. In a multiple
      logistic regression analysis, depth of coma on admission, multiple convulsions,
      and duration of unconsciousness were the only three independent risk factors.
      Hypoglycemia and lactate acidosis were not predictive of sequelae, although they
      are important risk factors for fatality. CONCLUSION: This finding raises the
      possibility that fatal outcome and neurologic sequelae arise from separate
      pathologic processes.

PMID- 9255204
TI  - Toxic shock syndrome without rash in a young child: link with syndrome of
      hemorrhagic shock and encephalopathy?
AB  - A diffuse macular erythroderma and subsequent desquamation after 1 to 2 weeks are
      two of the five major diagnostic criteria of toxic shock syndrome (TSS). We
      present the case of a 15-month-old girl with TSS, but without erythroderma or
      desquamation. She was admitted with high fever, shock, and multiorgan
      involvement. Minimal or no cutaneous signs were present. Initially the diagnosis
      of the syndrome of hemorrhagic shock and encephalopathy was made. After 7 days, a
      TSS toxin 1-producing strain of Staphylococcus aureus was cultured from an
      inguinal lymph node, where inflammation had already been noticed on admission.
      Moreover, the girl had no antibodies against this toxin. The serum cytokine
      profile during the acute phase of her illness showed high levels of tumor
      necrosis factor-alpha, interleukin-6 and interferon-gamma, as is seen during
      activation of the immune system by TSS toxin 1. Other possible causes for the
      patient's illness were excluded. We conclude that the patient had TSS without
      rash. Without the evidence implicating a TSS toxin 1-producing strain of S.
      aureus as the cause of her disease, a diagnosis of syndrome of hemorrhagic shock
      and encephalopathy would have been made. It is possible that some cases of
      syndrome of hemorrhagic shock and encephalopathy represent a variant of TSS in
      small children.

PMID- 9255205
TI  - Pelvic ultrasonography in patients with Turner syndrome: age-related findings in
      different karyotypes.
AB  - Real-time ultrasonography was performed in 142 patients with Turner syndrome,
      aged 0.57 to 21 years, with different karyotypes (45,X [4896], X mosaicism [17%],
      and X structural abnormalities [35%]). Ovarian and uterine volumes were
      calculated and the data collected in a mixed longitudinal and cross-sectional
      mode. Thirty-eight patients were followed longitudinally during pubertal age (10
      to 18 years bone age) for ovarian data. Patients with Turner syndrome were
      divided into two groups according to the presence or absence of detectable
      ovaries. Patients with Turner syndrome with detectable ovaries showed the first
      increase in ovarian volume at about 9 years of bone age; this increase was
      continuous and more evident only after 14 years of age and appeared later than in
      control subjects. When followed longitudinally during puberty, the ovaries showed
      a hormonal function in some cases. Girls with X mosaicism had the highest
      percentage of bilateral detectable ovaries and the greatest total ovarian volume;
      about 50% of them had spontaneous breast appearance and 38.5% had spontaneous
      menarche. They showed also the lowest gonadotropin levels, when bilateral ovaries
      were present during puberty. On the contrary, patients with the 45,X karyotype
      had the lowest percentage of detectable ovaries, ovarian volume, and spontaneous
      breast appearance. In our patients with Turner syndrome, uterine measures
      increased significantly with age and this was more evident in subjects with
      detectable ovaries after 13 years of bone age. Compared with control subjects,
      they showed significantly lower uterine measures, and patients with X mosaicism
      had greater and more progressive increments. In conclusion, pelvic
      ultrasonography in Turner syndrome is particularly useful in detecting ovaries
      and their possible increase in volume. These data, linked with karyotype pattern
      and gonadotropin levels, have prognostic value in predicting the future sexual
      development of these patients.

PMID- 9255206
TI  - Prospective multicenter study of sulfonylurea ingestion in children.
AB  - OBJECTIVE: Sixty-eight percent of pediatric sulfonylurea ingestions reported to
      poison centers do not result in laboratory or behavioral effects. Consequently,
      if all exposed children are admitted overnight or for 24 hours for these
      exposures, it will result in 600 to 700 hospital admissions per year of children
      who will remain free of symptoms. We prospectively studied exposures reported to
      10 regional poison centers to determine if it were possible to differentiate
      those patients who would have symptoms from those who would remain symptom free.
      METHODS: We analyzed all sulfonylurea exposures in children < or = 12 years old
      reported to the participating poison centers. Hypoglycemia was defined as blood
      glucose (BG) concentration < 60 mg/dl. RESULTS: Hypoglycemia developed in 56
      (30%) of 185 exposed patients. Fifty-four of the 56 (96%) hypoglycemic patients
      had development of hypoglycemia within 8 hours of ingestion. Eighty-seven of the
      patients were initially managed with oral supplementation only; in 13 cases,
      treatment advanced to intravenous administration of glucose or glucagon with the
      onset of hypoglycemia. There was no statistical difference in medical outcome
      between patients monitored during oral supplementation versus during intravenous
      infusion of dextrose. Ingestions analyzed by time of day did not predict risk of
      hypoglycemia. Sufficient data were available for 103 (58%) of the 177 patients
      who ingested glyburide or glipizide to calculate a toxic dose/weight ratio. Of
      these 103 patients, 31 of 36 patients who ingested < or = 0.3 mg/kg remained
      symptom free, whereas 31 of 67 who ingested more than 0.3 mg/kg had BG
      concentrations < 60 mg/dl (p < 0.005, 95% confidence interval 0.05 to 0.58;
      sensitivity 86%, specificity 46%). CONCLUSION: A lack of onset of hypoglycemia
      (BG > 60 mg/dl) in the first 8 hours after ingestion is predictive of a benign
      outcome in accidental pediatric sulfonylurea ingestion. Clinical observation of
      children for onset of hypoglycemia during oral feeding alone appears safe. Some
      children with symptoms of hypoglycemia need to receive intravenous dextrose
      therapy. Time of day of ingestion is not predictive of risk of hypoglycemia.
      Finally, at this time it appears inappropriate to use a milligram per kilogram
      body weight dose as a guide for management decisions.

PMID- 9255207
TI  - Defective antigen-induced lymphocyte proliferation in the X-linked hyper-IgM
      syndrome.
AB  - We examined T-cell proliferation in five patients with X-linked hyper-IgM
      syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired
      antigen-induced proliferation, whereas their lectin responses were normal. Thus,
      in addition to severely depressed antibody responses, patients with XHIM have a
      defect in antigen-specific T-cell proliferation, which may explain their
      susceptibility to pathogens such as Pneumocystis carinii.

PMID- 9255208
TI  - Transmission of varicella-vaccine virus from a healthy 12-month-old child to his
      pregnant mother.
AB  - A 12-month-old healthy boy had approximately 30 vesicular skin lesions 24 days
      after receiving varicella vaccine. Sixteen days later his pregnant mother had 100
      lesions. Varicella-vaccine virus was identified by polymerase chain reaction in
      the vesicular lesions of the mother. After an elective abortion, no virus was
      detected in the fetal tissue. This case documents transmission of varicella
      vaccine virus from a healthy 12-month-old infant to his pregnant mother.

PMID- 9255209
TI  - Sedation in children: adequacy of two-hour fasting.
AB  - OBJECTIVES: (1) To investigate the relationship between the duration of time that
      children fasted before a procedure and their gastric volume and pH at the time of
      the procedure. (2) To compare the variables of gastric pH and volume with
      historical standards. METHODS: We performed 285 gastroscopies for children aged
      0.1 to 18.6 years (mean, 7.5 +/- 5.3) between October 1991 and January 1995.
      Duration of fasting was 0.5 to 24 hours (mean, 6.7 +/- 5.3) after ingestion of
      clear liquids. Immediately after intravenously administered sedation, the gastric
      contents were removed endoscopically with suction and direct visualization to
      ensure complete evacuation. The volume and pH of the gastric contents were
      measured and analyzed in comparison with the duration of fasting. The values
      obtained were also compared with historical standards thought to minimize the
      risk of aspiration pneumonia: gastric volume 0.4 ml or less per kilogram of body
      weight and pH of 2.5 or greater. RESULTS: There was no significant correlation
      between duration of fasting and either gastric volume divided by body weight
      (mean, 0.68 +/- 1.31 ml/kg; range, 0 to 15.23 ml/kg) or pH (mean, 2.03 +/- 1.40;
      range, 1 to 8). There was less no significant difference in the percentage of
      children with gastric volume of 0.4 ml/kg or less or with pH of 2.5 or greater
      between the groups with the following fasting times: 30 minutes to 3 hours, more
      than 3 hours to 8 hours, and more than 8 hours. CONCLUSIONS: On the basis of the
      data in this study and a review of the literature, we concluded that (1) fasting
      longer than 2 hours after ingesting clear liquids does not significantly change
      gastric volume or pH, (2) there is no advantage in requiring children to fast for
      longer than 2 hours after clear liquid ingestion before sedation or anesthesia
      for any procedure, and (3) fewer than half of pediatric patients actually achieve
      the "desirable" values of a gastric volume of 0.4 ml/kg or less and a pH value of
      2.5 pH units or more, regardless of fast duration, even though these values are
      presented in the literature as a goal to minimize the risk of aspiration
      pneumonia.

PMID- 9255210
TI  - Disseminated varicella and staphylococcal pericarditis after topical steroids.

PMID- 9255211
TI  - Vertically transmitted babesiosis.

PMID- 9255212
TI  - Shprintzen-Goldberg syndrome results from mutations in fibrillin-1, not monosomy
      22q11.

PMID- 9255213
TI  - Near-fatal misdiagnosis of congenital adrenal hyperplasia.

PMID- 9255214
TI  - Cirrhosis in a child with deficiency of mitochondrial respiratory-chain succinate
      cytochrome c-oxidoreductase.

PMID- 9255215
TI  - Congenital cytomegalovirus infection with gastrointestinal involvement.

PMID- 9255216
TI  - Immunochemical staining in congenital cytomegalovirus-induced ileal ulceration.

PMID- 9255217
TI  - The not-so-good old days: working with pituitary growth hormone in North America,
      1956 to 1985.
AB  - Before 1985 the use of growth hormone (GH) was governed by a philosophy of
      scarcity and conservation of resources. Between 1956 and 1959 human pituitary GH
      was shown to be effective. The competition for gland collection and extraction
      that followed benefited only certain patients with motivated parents and only a
      few investigators. To maximize gland collection, the distribution of GH for
      clinical investigation, and the number of patients who could be treated, the
      National Institutes of Health and the College of American Pathologists formed the
      National Pituitary Agency (NPA). In Canada a similar program was developed by the
      Canadian Medical Research Council. For more than 20 years the NPA supervised most
      of the GH treatment in the United States. Commercial pituitary GH entered the
      U.S. market in 1976, and competition soon appeared. Patients treated through the
      NPA were subjects in clinical studies for part of the first year of treatment,
      after which the limited availability of GH dictated treatment for only part of
      the year and caps on final heights. By 1984 treatment was year round and the
      height caps largely unenforced. In the last year of its distribution NPA GH was
      used in 2450 patients in the United States and commercial pituitary GH was used
      in 600 to 800; slightly more than 300 patients were being treated in Canada. And
      then, in 1985, came Creutzfeldt-Jacob disease. While the not-so-good old days are
      gone and need not be lamented, there remains virtue in a conservative therapeutic
      philosophy. If anything can be learned from the use of pituitary GH in children,
      it is a healthy respect for the law of unintended consequences.

PMID- 9255218
TI  - Pioneering recombinant growth hormone manufacturing: pounds produced per mile of
      height.
AB  - The first efforts to produce recombinant human growth hormone (GH) for clinical
      use were begun by scientists at Genentech, Inc., almost a generation ago, late in
      1979. The very small market for GH that was predicted at the time led to this
      manufacturing effort being done as a demonstration project. Among the early
      issues was whether the Escherichia coli host cell could be routinely produced in
      a stable manner and be inactivated after the GH production run (as required by
      Federal guidelines) without the GH being permanently denatured. A 10 L E. coli
      process was developed, and phase I testing began in early 1981. The approval of
      this recombinant GH product by the FDA in 1985 paved the way for many
      improvements and a sustained production effort in the next decade. The more than
      1990 fermentation runs have produced tons of E. coli and more than 130 pounds of
      GH for both clinical research and the treatment of severely short children.

PMID- 9255219
TI  - Disorders of puberty: inactivating and activating molecular mutations.
AB  - Recent developments have increased our understanding of the molecular mechanisms
      that are responsible for several disorders of puberty. Specific gene mutations
      have been identified in three syndromes, one that is associated with delayed
      puberty (Kallmann syndrome) and two that are associated with precocious puberty
      (McCune-Albright syndrome and familial male precocious puberty). Mutations in the
      KAL gene have been shown to be responsible for cases of X-linked Kallmann
      syndrome. This gene encodes a protein that is believed to be involved in neural
      target recognition and protease inhibition. In McCune-Albright syndrome,
      heterozygous, postzygotic somatic mutations of the alpha-subunit of the
      stimulatory guanine nucleotide binding protein Gs have been shown to stimulate
      constitutive G protein activation and long-term cyclic adenosine monophosphate
      production. Similarly, familial male precocious puberty has been linked to gain
      in-function mutations that result in increased levels of cyclic adenosine
      monophosphate; however, these mutations are found in the luteinizing hormone
      receptor gene itself. The clinical manifestations and the recent molecular
      advances in each of these three syndromes are explored.

PMID- 9255220
TI  - Effects of renal failure on the growth hormone-insulin-like growth factor axis.
AB  - Children with chronic renal failure (CRF) often have retarded growth, and
      abnormalities of the growth hormone-insulin-like growth factor (GH-IGF) axis in
      CRF may contribute to this growth failure. The serum GH and IGF levels are normal
      in these children, but IGF bioactivity is low as a result of excess IGF binding
      proteins (IGFBPs) in the 35 kd serum fractions. The levels of intact IGFBP-1, -2,
      and -6 and of a 29 kd IGFBP-3 fragment are all high, and the IGFBP-1 and -2
      levels correlate negatively with height. Children with CRF who are treated with
      GH show catch-up growth that correlates positively with the increase in each
      component of the 150 kd serum ternary complex (acid-labile subunit, IGFBP-3, IGF
      I, and IGF-II). Consistent with this observation, the increase in IGFBP-3 levels
      is confined to the 150 kd serum fractions. Serum levels of IGFBP-1, -2, and -6 do
      not rise, but serum IGF bioactivity does. Thus GH appears to induce an increase
      in the ternary complex in the serum of children with CRF. It is possible that
      IGFs released by the 150 kd serum complex promote growth by overcoming the
      inhibitory effects of excess IGFBPs in the 35 kd serum fractions.

PMID- 9255221
TI  - Effects of growth hormone and insulin-like growth factor I on renal growth and
      function.
AB  - Polypeptide growth factors regulate kidney development, growth, and function and
      participate in the repair processes after renal injury. The use of one or more
      growth factors as therapeutic agents in the settings of acute and chronic renal
      failure has been proposed. Insulin-like growth factor I (IGF-I) accelerates the
      restoration of kidney function and the normalization of structure and reduces
      mortality rates in animal models of acute renal injury. The mechanisms by which
      IGF-I acts in acute renal failure include stimulation of anabolism, maintenance
      of glomerular filtration, acceleration of tubular regeneration, and increased
      expression of ischemia-induced renal genes. It has been safely used in persons at
      risk of having acute renal failure and in patients with end-stage chronic renal
      failure, in whom it increases the glomerular filtration rate. Further studies to
      determine the role of IGF-I as a therapeutic agent for acute renal failure and
      its utility as a medical therapy for chronic renal insufficiency are required.

PMID- 9255222
TI  - Growth-hormone treatment of renal transplant recipients: the National Cooperative
      Growth Study experience--a report of the National Cooperative Growth Study and
      the North American Pediatric Renal Transplant Cooperative Study.
AB  - OBJECTIVE: To evaluate growth response and renal allograft measures after
      recombinant human growth-hormone (GH) treatment in pediatric renal transplant
      recipients. STUDY DESIGN: Data on GH-treated children in the National Cooperative
      Growth Study (NCGS) database were linked to the database of the North American
      Pediatric Renal Transplant Cooperative Study (NAPRTCS). Data were analyzed for
      growth rate, graft survival, graft function, acute rejection, and adverse events.
      Data on 2390 transplant recipients in the NAPRTCS who had at least 24 months of
      graft function were used in the comparisons. RESULTS: Fifty-nine patients were
      treated with GH after renal transplantation. One-year growth data were available
      for 42 of these; 2-year, for 31; and 3-year, for 13. Growth velocity increased
      from 2.47 +/- 1.83 cm/yr to 7.17 +/- 2.97 cm/yr after 1 year. Year-2 and -3
      growth rates were 5.93 +/- 2.29 cm/yr and 6.31 +/- 2.32 cm/yr. Height standard
      deviation score immediately after transplantation was -3.26 +/- 1.44 and at the
      initiation of GH was -3.59 +/- 1.15; it increased to -3.18 +/- 1.06 at year 1 and
      to -3.16 +/- 0.92 at year 2 and was -3.31 +/- 1.00 at year 3. Five-year graft
      survival was 80% in the GH cohort and 85% in the NAPRTCS cohort. Acute rejection
      ratio was 1.44 and 1.43 episodes per patient in the GH and NAPRTCS cohorts,
      respectively. Calculated creatinine clearance at 6 years was 68 and 63 ml/min per
      1.73 m2, respectively. CONCLUSIONS: Growth hormone increase growth velocity for
      up to 3 years without an apparent decrease in graft survival or renal function,
      and no relation between GH therapy and acute rejection is seen. A randomized,
      prospective study to evaluate further the safety and efficacy of this promising
      therapy is required.

PMID- 9255223
TI  - Growth hormone is not safe for children with renal transplants.
AB  - Growth failure is an important problem in children with renal failure. Even after
      renal transplantation their growth rates may be lower than normal, and "catch-up"
      growth does not occur. Therefore there is great interest in giving growth hormone
      (GH) after transplantation. Clinical observations and theoretic considerations
      call into question whether GH after transplantation is safe. Studies have shown a
      more rapid than normal decline in renal function after the initiation of GH
      therapy. This result could be explained by the effects of GH on the immune
      response. Growth hormone is known to modulate (usually upregulate) the immune
      response and could be a reason for the increased loss of renal function caused by
      rejection. It could also be explained by the long-term effects of GH on the
      injured kidney. Experimental data (generally not in the transplantation model)
      suggest that exogenous GH given after renal injury or reduced renal mass leads to
      a more rapid development of glomerular sclerosis and reduced renal function. GH
      should not be administered to children after renal transplantation until all
      safety questions have been answered in prospective clinical trials.

PMID- 9255224
TI  - Growth hormone is safe in children after renal transplantation.
AB  - With the availability of an easily produced and safely administered form of
      recombinant human growth hormone (GH), the clinical indications for its use have
      increased. Recent studies have shown that GH therapy is both safe and effective
      in the treatment of growth failure in children with chronic renal insufficiency.
      Similarly, GH has been used to treat growth failure in children after renal
      transplantation. GH therapy increases growth in these patients, but in some of
      them increased organ rejection or worsening of kidney function occurs. GH is a
      neuroendocrine peptide that is important to somatic growth, but it has also been
      shown to have pleiotropic effects on many cells and organ systems including the
      immune system. We have shown that GH in vitro augments the responses during a
      mixed leukocyte culture in normal adult volunteers. GH also augments the
      responses to donor-specific alloantigens in some patients. We conclude that if in
      vitro assays such as these can successfully identify those patients who are at
      risk for organ rejection and worsening kidney function, then GH therapy is safe
      in children with growth failure after renal transplantation.

PMID- 9255225
TI  - Risk of leukemia in children treated with human growth hormone: review and
      reanalysis.
AB  - BACKGROUND: Data have suggested that any increased incidence of leukemia in
      growth-hormone (GH)-treated patients was limited to those with known risk factors
      for leukemia. However, previous studies may have overestimated the numbers of
      patient-years of risk by not excluding data from "positive-risk-factor" patients.
      This risk was reanalyzed by using data on children in the National Cooperative
      Growth Study (NCGS), with correction for this possible confounding factor.
      METHODS: The risk of leukemia in GH-treated patients without known risk factors
      was determined by using patient-years of GH therapy and patient-years since first
      exposure to GH therapy and the values obtained were compared with values from the
      Surveillance, Epidemiology, and End Results program of the National Cancer
      Institute. RESULTS: Three cases of leukemia in patients without known risk
      factors were found in the NCGS database; 3.42 cases would be expected in the
      119,846 patient-years in the analysis using time since GH exposure. Two of these
      cases of leukemia occurred during GH therapy (67,773 patient-years); 2.13 cases
      would be expected. CONCLUSION: Excluding data on patients with known risk factors
      for leukemia provides a more accurate estimate of the risks in GH-treated
      patients. The incidence of leukemia in these patients is comparable to that in
      the general population of age-matched children.

PMID- 9255226
TI  - Endocrine late effects of childhood cancers.
AB  - Long-term survival in children with cancer has increased markedly in the past 15
      years. However, impaired linear growth and thyroid dysfunction that vary
      according to the age at diagnosis and treatment and to the dose and duration of
      radiation and chemotherapy have been described in these patients. The impact of
      cranial irradiation on the hypothalamic-pituitary-adrenal axis and on pubertal
      maturation has been less well studied. A positive correlation between the age at
      diagnosis and the age at onset of puberty in children who have been treated with
      high-dose cranial radiation therapy for central nervous system (CNS) tumors has
      been found recently. Frank adrenal insufficiency is uncommon after high-dose CNS
      irradiation, but alterations in the hypothalamic-pituitary-adrenal axis do occur.
      Assessments of the effects of newer modes of radiation therapy such as
      hyperfractionated craniospinal radiation suggest a lower incidence of primary
      hypothyroidism in the long term.

PMID- 9255227
TI  - Growth-hormone signal transduction.
AB  - Growth hormone (GH) has long been recognized as one of the principal factors that
      control postnatal growth. Advances made in the last 5 years have increased our
      understanding of the intracellular signaling mechanisms subsequent to GH binding.
      The earliest event in GH signaling appears to be the binding of a single GH
      molecule by a pair of GH receptors (GHRs). The dimerization of GHRs leads to the
      activation of Janus kinase 2 (JAK2), a nonreceptor tyrosine kinase that
      associates with the cytoplasmic domain of GHR. It is thought that all signaling
      downstream from GHR depends on this initial activation of JAK2. Once activated,
      JAK2 tyrosyl-phosphorylates both itself and the cytoplasmic domain of GHR. These
      phosphorylated tyrosine residues act as docking sites for various signaling
      molecules that contain Src homology 2 (SH-2) or other phosphotyrosyl-binding
      domains. The signaling molecules that are recruited and activated by the GHR-JAK2
      complex include signal transducers and activators of transcription (Stat)
      factors, the adapter protein Shc, and the insulin receptor substrates (IRSs) 1
      and 2. The recruitment and activation of these signaling intermediates leads to
      the activation of enzymes such as MAP kinase, phosphatidylinositol-3'-kinase,
      protein kinase C, and phospholipase A2 and to the release of various second
      messengers such as diacylglycerol, calcium, and nitric oxide. Ultimately, these
      pathways modulate cellular functions such as gene transcription, metabolite
      transport, and enzymatic activities that affect the GH-dependent control of
      growth and metabolism.

PMID- 9255228
TI  - The spectrum of growth-hormone insensitivity.
AB  - OBJECTIVES: To summarize the steps that led to the recognition of the Laron
      syndrome of growth-hormone (GH) insensitivity as a recessive disorder that is
      caused by mutations in the growth hormone receptor (GHR) gene, to discuss the
      different types of mutations that have been found in the GHR gene, and to examine
      whether the degree of growth impairment in affected homozygotes depends on the
      specific type of GHR mutation. RESULTS: A broad spectrum of abnormalities in the
      GHR gene have been reported. These abnormalities range from deletions of multiple
      exons, through deletions of a small number of base pairs, nonsense mutations,
      missense mutations that alter GH-binding affinity or impair receptor processing,
      to mutations that exert their deleterious effects by altering messenger RNA
      splicing and result in the loss of portions of the GHR. CONCLUSIONS: Different
      abnormalities in the GHR gene have different effects on the concentrations of
      circulating GH-binding protein that represents the extracellular portion of the
      GHR. Homozygosity or compound heterozygosity for the different mutations produces
      a fairly uniform phenotype of severe postnatal growth retardation. The
      differences in height standard deviation scores between persons appear to depend
      more on age, sex, and nutritional status than on the specific type of GHR
      mutation.

PMID- 9255230
TI  - National Cooperative Growth Study substudy VI: the clinical utility of growth
      hormone-binding protein, insulin-like growth factor I, and insulin-like growth
      factor-binding protein 3 measurements.
AB  - OBJECTIVE: To assess the clinical utility of growth-hormone-binding protein
      (GHBP), along with growth hormone (GH), insulin-like growth factor I (IGF-I), and
      insulin-like growth factor-binding protein 3 (IGFBP-3), levels in the evaluation
      of short stature. STUDY DESIGN: Prospective substudy of the National Cooperative
      Growth Study, a multicenter observational study. RESULTS: A total of 6447
      assessable subjects undergoing workup for short stature were enrolled at 197
      sites. At baseline the cause of short stature was undefined in 77% of subjects.
      Mean GHBP levels were lowest in subjects with renal disease and highest in those
      with Turner syndrome. No cases of complete GH insensitivity syndrome (Laron
      syndrome) were identified. Subjects with low GHBP levels were among those tested
      for GH receptor mutations. IGF-I standard deviation scores (SDS) and IGFBP-3 SDS
      were positively correlated; both increased during GH therapy. There was a weak
      positive correlation between log peak GH levels and both IGF-I SDS and IGFBP-3
      SDS and a weak negative correlation between log peak GH levels and GHBP SDS. Mean
      changes in GHBP SDS in subjects treated with GH and untreated subjects were not
      significant. Change in height SDS in subjects treated with GH was negatively
      correlated with age and IGF-I level but not correlated with baseline GHBP SDS.
      CONCLUSION: GHBP levels are GH independent and not predictive of responses to GH
      therapy, although low GHBP levels may indicate GH receptor abnormalities and
      partial GH insensitivity.

PMID- 9255229
TI  - Partial growth-hormone insensitivity: the role of growth-hormone receptor
      mutations in idiopathic short stature.
AB  - Mutations in the GHR locus may play a role in the cause of idiopathic short
      stature (ISS) by impairing growth-hormone (GH) receptor (GHR) function. At one
      extreme, mutations that nullify the function of the GH receptor are linked to
      complete GH insensitivity syndrome, or Laron syndrome, and we hypothesized that
      less-disruptive mutations could contribute to partial GH insensitivity syndrome.
      Low levels of GH binding protein may indicate mutations in the extracellular
      domain of the receptor, and by focusing on 14 children with ISS who had low GH
      binding protein and insulin-like growth factor I levels, we found three
      heterozygotes and one compound heterozygote for mutations in the extracellular
      domain of the receptor. We have since extended our study to a broader spectrum of
      patients, adding 76 patients with ISS who were treated with GH in a phase II
      study of the safety and efficacy of recombinant human GH in ISS and also adding
      10 patients who were ascertained as having ISS by pediatric endocrinologists in
      private practice. The GHR gene has thus been analyzed in 100 patients with ISS,
      eight of whom were found to carry mutations: four in our original study and four
      with normal or elevated levels of GH binding protein. The latter group consists
      of three carriers of heterozygous extracellular domain mutations and one carrier
      of a heterozygous intracellular domain mutation. Family data suggest that the
      carriers of these mutations have a range of phenotypes, supporting our hypothesis
      that the expression of these heterozygous mutations as partial GH insensitivity
      syndrome depends on the genetic makeup of the person.

PMID- 9255232
TI  - Effects of growth hormone treatment in children with cystic fibrosis: the
      National Cooperative Growth Study experience.
AB  - Poor longitudinal growth and low body weight affect many persons with cystic
      fibrosis (CF). The Cystic Fibrosis Foundation reports that 28% of all persons
      with CF are below the 10th percentile for height and that 34% are below the 10th
      percentile for weight. Intensive nutritional supplementation has not resulted in
      sustained improvement in the poor linear growth and low weight in CF. Because of
      the significant impact of nutrition in CF, the anabolic effects of growth hormone
      (GH) may make the agent useful as adjunctive treatment for malnutrition and poor
      linear growth. To date, 24 patients with CF (16 boys; 87% Tanner stage 1) have
      been enrolled in the National Cooperative Growth Study. The average age at
      enrollment was 10.3 years, and there was significant delay in height in all
      patients (mean height age, 7.1 years). Bone age was also significantly delayed
      (mean delay, 3.0 years). The mean maximum stimulated GH level was 12.3
      micrograms/L and the mean GH dose given was 0.291 +/- 0.038 mg/kg per week. After
      1 and 2 years of treatment with GH the growth rate increased in all patients with
      available growth rate data. The growth rates in these children were slightly
      lower than in children who were treated with GH for idiopathic GH deficiency. The
      weight-for-height standard deviation scores improved significantly after 2 years
      of GH treatment. There were adverse reactions (glucose intolerance) to GH in only
      two patients; treatment was suspended in one of these patients but was continued
      in the other. National Cooperative Growth Study data indicate that treatment with
      GH increases linear growth and weight in prepubertal patients with CF. These data
      suggest that GH may be useful for treating malnutrition in CF.

PMID- 9255231
TI  - Making a rational diagnosis of growth-hormone deficiency.
AB  - Growth hormone (GH) has been available for therapeutic use for more than 30
      years, but there is still considerable debate about the best way to diagnose GH
      deficiency. This can be attributed to the existence of a variable degree of GH
      insufficiency in most cases and the fact that assays vary considerably between
      laboratories in terms of sensitivity and epitope specificity. These difficulties
      are compounded by the episodic nature of GH secretion and our reliance on a
      variety of provocative tests. A workshop and consensus report held in Portland,
      Oregon, in 1995 highlighted these issues and suggested a rational diagnostic
      approach that emphasizes good auxologic evidence, followed by assays of insulin
      like growth factor I and insulin-like growth factor binding protein 3 to identify
      abnormalities in the GH axis. Actual assays of GH, during some provocative tests,
      are relegated to confirming that an identified abnormality in the GH-insulin-like
      growth factor axis is related to GH insufficiency rather than to GH resistance.

PMID- 9255233
TI  - Is growth hormone good for the heart?
AB  - Growth hormone (GH), probably acting indirectly through locally produced insulin
      like growth factor I, stimulates myocardial hypertrophy and increases myocyte
      contractility. In experimental models insulin-like growth factor I appears to be
      a key regulator of ventricular hypertrophy. Many adults with growth hormone
      deficiency (GHD) have reduced left ventricular mass, a lower ejection fraction,
      and reduced exercise tolerance. Elevated serum lipid levels, increased visceral
      fat, and early atheroma formation may contribute to an increased mortality rate
      from cardiovascular disease in these persons, but GH replacement therapy appears
      to correct many of these abnormalities. GH excess (acromegaly) results in cardiac
      hypertrophy that can progress to cardiac failure. Treatment with octreotide at
      least partially reverses cardiac hypertrophy and dysfunction. GH treatment may
      induce beneficial cardiac hypertrophy in adults without GHD who have dilated
      cardiomyopathy. Significant cardiac dysfunction has not been reported in children
      with GHD who are treated with GH, nor have adverse cardiac effects been reported
      with GH in short children without GHD, including those with Turner syndrome. We
      now have extensive experience with the therapeutic use of GH in children with
      cardiac structural abnormalities (e.g., Turner and Noonan syndromes, congenital
      heart disease), and such use appears to be safe. Furthermore, cardiac
      complications of GH in children without cardiac disease are rare. Continued
      observation to ensure that GH therapy has no long-term effects on cardiac anatomy
      or function in children is necessary.

PMID- 9255234
TI  - Exercise and growth hormone: does one affect the other?
AB  - The release of growth hormone (GH) is sensitive to many pharmacologic and
      physiologic stimuli, including exercise. Although the role of the increased
      amount of GH released during exercise is not fully understood, it most likely
      contributes to metabolic fuel adaptations during exercise, and tissue repair
      after the exercise session. The GH response to exercise is altered by many
      factors, including sex steroid concentrations, fitness level, and the intensity
      of previous exercise sessions. For both endurance and resistance exercise,
      greater activation of anaerobic glycolysis and lactate formation increases the
      amount of GH released. Whether an endurance exercise session or an endurance
      exercise training regimen influences the total amount of GH released during a 24
      hour period is not clear; this may depend on the gender of the person, the
      intensity of the exercise, and the duration of exercise training. The influence
      of a single session of resistance exercise or resistance training on 24-hour GH
      secretion has not been studied. Preexercise diet modulation (especially
      modulation of fat intake) may also influence the release of GH during endurance
      exercise. Studies that measure the 12- to 24-hour GH response to resistance
      exercise after the ingestion of various macronutrient diets have not been
      completed.

PMID- 9255236
TI  - Tiludronate for Paget's disease of bone.

PMID- 9255235
TI  - National Cooperative Growth Study substudy VIII: a new look at the natural
      history of short stature.
AB  - National Cooperative Growth Study (NCGS) substudy VIII was designed to determine
      the characteristics of children who are referred to pediatric endocrinologists
      for evaluation of short stature but are not treated with growth hormone (GH). No
      specific course of treatment is required to enter the study. Data on the
      subjects' characteristics at enrollment, the diagnostic procedures used by the
      investigators, and the occurrences of various medical conditions and intercurrent
      illnesses will be collected prospectively and will be compared with the
      corresponding data on children in the NCGS who are treated with GH.

PMID- 9255237
TI  - Fosfomycin for urinary tract infections.

PMID- 9255238
TI  - Drugs for non-HIV viral infections.

PMID- 9255239
TI  - [Evaluation of a test for rapid detection of D-dimers for the exclusion of the
      diagnosis of venous thrombosis].
AB  - OBJECTIVES: The SimpliRED whole blood D-dimer assay for exclusion of deep venous
      thrombosis in symptomatic outpatient appears to be a simple and rapid method; we
      wanted to confirm its reliability. METHODS: Fifty consecutive outpatients (mean
      age 57, range 20 to 89) referred to our department between September and December
      1996, for clinically suspected deep venous thrombosis (DVT) were included.
      Hospitalized patients were excluded as well as patients under anticoagulant and
      pregnant women. DVT was diagnosed with our usual strategy of compression
      ultrasonography at the levels of the common femoral, the superficial femoral and
      the popliteal veins including the exploration of sural and saphenous veins. The D
      dimer assay was performed, according to the manufacturer recommendation, blindly
      by a physician unaware of the results of ultrasonography within one hour.
      RESULTS: Eight of nineteen patients with DVT had a normal D-dimer test result
      Four had a sural DVT, but four had a proximal DVT. Furthermore four patients with
      normal D-dimers had superficial venous thrombosis. CONCLUSIONS: Our series does
      not confirm the high sensitivity and negative predictive value reported
      previously. To date it is premature to propose this assay as a first line test in
      the therapeutic management of patients with suspected DVT.

PMID- 9255240
TI  - [Epidemiological approach of inhibition in general practice].
AB  - OBJECTIVE: To obtain preliminary data on the prevalence and characteristics of
      inhibition in an adult population consulting in general practice. PATIENTS AND
      METHODS: Eight hundred thirteen general practitioners, forming a representative
      distribution of general medicine clinics in France. Each evaluated, during a
      study period which did not exceed 2 days in 70% of the cases, 20 consecutive
      patients using a standard questionnaire, noting age, sex, motivation for
      consultation, presence of inhibition, inhibition score, and associated diseases
      (5 were possible). The physicians also scored 12 specific items (attitude,
      fatigue, feeling of being "blocked", concentration, memory, planning, indecision,
      inefficiency, creativity, sleep, appetite, sexuality) (0 = absent; 1 = discrete;
      2 = moderate). The sum of the scores provided the global inhibition score
      (maximum = 24). RESULTS: Among the 15076 patients evaluated (M/F ratio 41.3/58.7;
      mean age 49.4 +/- 18 years; educational level: French aptitude certificate 44%)
      one or more of the inhibition items was the motivation for consultation in 23.9%
      and at least one item was scored in 80% of the cases. Fatigue was scored in more
      than half the patients. The percentage of patients considered to be inhibited (I)
      was 35.8% (M/F ratio 35.3/64.7; mean age 51.9 +/- 18 years). Compared with the
      non inhibited population (NI), the items most frequently associated with and most
      characteristic of inhibition were severe fatigue (I = 42.4% vs 8.7 NI), sleep
      disorders, difficulties in concentrating or memory, and a feeling of being
      "blocked". The symptom intensity score was 2.9 +/- 3.3, 10.9 +/- 5 and 15.9 +/-
      4.7 in populations NI, I and PI (patients considered to be the most inhibited)
      respectively. This suggested that there is a correlation between a high score and
      presence of inhibition and its intensity. Anxiety was invariably described in all
      three subpopulations, but depression was the most discriminating factor (3.7,
      33.9, and 67.2 for NI, I and PI respectively). CONCLUSION: These preliminary data
      show an unsuspected high frequency of inhibition in patients consulting in
      general practice. Inhibition was more frequently observed in women and in older
      patients inhibition showed a characteristic physical, intellectual and psychic
      symptomatology dominated by fatigue and increased in intensity when associated
      with a depressive syndrome.

PMID- 9255241
TI  - [Intracranial aneurysm and coronary ectasia].
AB  - BACKGROUND: Coronary aneurysms are uncommon and can exceptionally be associated
      with other aneurysmal localizations. CASE REPORT: A 34 year-old man with a
      history of aneurysm of the coronary arteries revealed by myocardial infarction
      without a wave six months earlier, presented cerebral hemorrhage secondary to an
      aneurysmal rupture of the anterior communicating artery. DISCUSSION: Other
      aneurysmal localizations such as the abdominal artery, pulmonary artery, hepatic
      artery, popliteal artery, coronary venous system or the left ventricle have been
      associated with coronary artery aneurysm. Only one case of coronary and cerebral
      aneurysm has been previously reported in the literature in an 8-year-old child
      with X-linked lymphoproliferative syndrome and EBV-induced infectious
      mononucleosis. Our case suggests that systemic aneurysmal disease may be a
      clinical entity and that cerebral angiogram should be discussed in patients with
      a coronary artery aneurysm.

PMID- 9255242
TI  - [Motor neuron syndrome and Lyme disease. Relation of causality or fortuitous
      association?].

PMID- 9255243
TI  - [Sarcoidosis occurring after breast cancer].

PMID- 9255244
TI  - [Streptococcus constellatus cerebral abscess in a patient with HIV infection].

PMID- 9255245
TI  - [What vasoactive agent should be chosen in rupture of esophageal varices in
      cirrhosis?].
AB  - Variceal esophageal bleeding is a frequent and severe complication of portal
      hypertension. Balloon compression was the standard therapy for many years.
      Currently, endoscopic hemostasis with sclerosis or ligation appears to be more
      effective but requires an experienced operator who is not always present at
      emergency situations. Parenteral administration of vasoactive agents is one
      therapeutic option offering new perspectives for the future. Data in the
      literature suggest that terlipressin or somatostatin would be the preferential
      choice because of the adverse effects of vasopressin. Data is insufficient
      concerning sandostatin. Currently, the trend is to administer vasoactive agents
      as soon as possible, prior to hospitalization and, perhaps, in association with
      endoscopic hemostasis. Treatment should be maintained for several days although
      the cost/benefit ratio remains a question of debate.

PMID- 9255246
TI  - [Statistics of mortality in 1994 and predictions of death caused by cancer 1997].
AB  - The latest mortality statistics available in France, for 1994, are presented and
      show that the first cause of death was cardiovascular disease (32%) followed by
      cancer (27%). Previsional estimations for 1997 reveal that in men, there will be
      an expected 85,000 deaths from cancer, the first cause of mortality in men, the
      first three localizations being lung cancer (24%), prostate cancer (11%) and
      colorectal cancer (10%). In women, there will be an estimated 55,000 deaths due
      to cardiovascular disease, the primary cause of mortality. Breast cancer is
      expected to be the number one cause of death by cancer (20%) followed by
      colorectal cancer (14%) and lung cancer (7%).

PMID- 9255247
TI  - [Role of behavioral and cognitive techniques in the treatment of schizophrenia].
AB  - PRAGMATIC APPROACH: For patients with schizophrenia, improvement does not simply
      mean freedom from delirium, but also implies the acquisition of the personal and
      relational skills needed for durable stabilization. Consequently, behavioral and
      cognitive therapies have progressively gained a specific role in the treatment of
      schizophrenia. BASIC PRINCIPLES: Behavior and cognitive techniques proposed for
      rehabilitating patients with schizophrenia are based on acquisition of social
      skills which the patients can use to manage their treatment and their daily
      familial and interpersonal relationships. FAMILY THERAPY: The aim of family
      therapy is to improve the emotion expressed within a family by improving the
      family's capacity for intercommunication, coherence and adaptation to the
      patient's situation. This individual and familial approach to behavior can
      provide substantial prolonged benefit for the schizophrenic patient. A PRECIOUS
      CONTRIBUTION TO THERAPEUTICS: The organization of behavioral and cognitive
      therapy requires long-term adhesion from patients, health cares and family. In
      combination with adapted drug therapy and with individually designed objectives,
      behavioral and cognitive therapies can widen the therapeutic spectrum proposed in
      this chronic and difficult to manage disease.

PMID- 9255248
TI  - [Intrahepatic porto-systemic shunt in the treatment of hemorrhage in portal
      hypertension].
AB  - PREVENT RECURRENT BLEEDING: Digestive hemorrhage due to portal hypertension is
      the cause of one-third of the mortality in cirrhosis. Transjugular intrahepatic
      portosystemic shunt (TIPS) creates a calibrated anastomosis between the portal
      vein and hepatic vein. The technique is now well established and a trained team
      can install a shunt in approximately 2 hours with a risk of failure of less than
      10%. RESULTS: TIPS can be effective for the treatment and prevention of variceal
      bleeding subsequent to portal hypertension. Preliminary results have not however
      provided the precise indications for this technique in the therapeutic
      armamentanium. COMPLICATIONS: Hepatic encephalopathy and obstruction are the main
      complications. Encephalopathy can occur as an acute episode; frequency appears to
      fall off after endothelialization of the prosthesis. The degree of shunt
      obstruction can reach 40% at one year and remains the major problem with this
      technique. Its pathogenesis is unknown and there is no prevention. Regular
      surveillance is required to detect this complication and take the necessary
      steps.

PMID- 9255249
TI  - [Psoriasis today].
AB  - PATHOGENESIS: Psoriasis is a proliferative disease of the epiderm which leads to
      major disorders in keratinocyte differentiation. The pathogenesis remains largely
      unknown. It has been hypothesized that intrinsic alterations of the keratinocyte
      or local or general immune disorders could be involved. GENES IMPLICATED:
      Psoriasis is a genodermatosis which is revealed or aggravated by environmental
      factors. The nature and chromosomal localization of the genes involved is
      currently under study. LOCAL TREATMENT: Over the last years, use of vitamin D has
      largely replaced former topical corticosteroid therapy. Phototherapy using narrow
      spectrum ultraviolet B is currently the standard treatment for extensive
      psoriasis. GENERAL TREATMENT: Methotrexate, retinoids and cyclosporin are
      effective in severe psoriasis but have side effects which limit their
      indications.

PMID- 9255250
TI  - Renal oncocytoma: a clinicopathologic study of 70 cases.
AB  - We reviewed 954 primary nonurothelial epithelial renal neoplasms with primary
      resection at Memorial Sloan-Kettering Cancer Center between the years 1980 and
      1995 and classified 70 cases (7%) as renal oncocytomas. The study population was
      composed of 39 men and 31 women, and the mean age was 65 years (range 25 to 86
      years). Fifty-six patients (80%) were asymptomatic at presentation, six (4%) had
      flank pain, six (4%) presented with a mass, and two (3%) had hematuria. Sixty-one
      were treated with total or radical nephrectomy, nine with partial nephrectomy.
      The right kidney was involved in 35 cases (50%), the left kidney in 32 (46%).
      Three cases (4%) were bilateral. Sixty-one cases (87%) were unifocal, nine (13%)
      multifocal. All the tumors were well circumscribed but unencapsulated. Forty-five
      (64%) were described as brown or red, whereas the remainder were variously
      described as tan to yellow. Central fibrosis or scar was described in 23 cases
      (33%), and gross areas of hemorrhage or cystic changes in 14 (20%). The mean size
      was 5.2 cm and median 5.0 cm (range 1.5 cm to 14 cm). Histologically, the tumors
      were characterized by a mixture of architectural patterns: compact cellular nests
      and acini embedded in a hyalinized, hypocellular stroma were present in 62 cases
      (89%), a solid nested architecture in 47 cases (67%), and a variable tubular
      component in 50 cases (71%). Small papillae, pseudopapillae, and intratubular
      epithelial tufts were seen in 19 cases (27%). Cytologically, the neoplasms also
      showed a mixture of cell types, the most common being the classic oncocyte, which
      consisted of round or polygonal cells with moderate to abundant granular,
      eosinophilic cytoplasm, and small round nuclei with evenly dispersed granular
      chromatin. Small basophilic nucleoli were visible in many of these cells in all
      cases. Thirty-one cases (44%) had a variable number of oncocytic cells with
      pyknotic nuclei and 20 (30%) contained clusters of small cells with a high
      nuclear/cytoplasmic ratio and dense hyperchromatic nuclei (so-called oncoblasts).
      Foci of tubules with clear cells embedded in a hyalinized stroma were present in
      six cases (9%). Cellular atypia was evident in 42 cases (60%) and was marked in
      21 (30%). Eleven cases (16%) exhibited mitotic activity, albeit low. No case had
      atypical mitoses or necrosis. Twenty-two cases (31%) had areas of calcification
      within the hyalinized stroma, 12 (17%) had calcospherites, and three (4%) had
      osseous and myeloid metaplasia. Vascular invasion was present in three cases
      (4%), and invasion of perinephric fat in 14 (20%). One patient presented with
      liver metastasis. Fourteen cases (20%) were pT1, 42 (60%) pT2, and 14 (20%) pT3.
      After a mean follow-up of 58 months (range 1 to 181), 62 patients (89%) were
      alive with no evidence of tumor, six (9%) had died of other causes, one was alive
      with stable metastatic disease in the liver 58 months after diagnosis, and one
      died with metastatic disease to bone and liver. We conclude that renal
      oncocytomas have a varied morphologic appearance and their pathologic diagnosis
      should be based on a constellation of architectural and cytologic features. The
      overwhelming majority of cases behave in a benign fashion, although in rare
      instances they can metastasize. The presence of atypical morphologic features do
      not alter the excellent prognosis associated with oncocytomas and do not predict
      an aggressive clinical course.

PMID- 9255251
TI  - Lymphocyte-rich well-differentiated liposarcoma: report of nine cases.
AB  - Nine well-differentiated liposarcomas with foci simulating the appearance of
      malignant lymphoma and other lymphoid disorders are reported. Their clinical
      presentation and evolution were not significantly different from those of their
      conventional counterparts lacking a lymphoid infiltrate. Microscopically, these
      tumors were characterized by areas of ordinary well-differentiated liposarcoma,
      admixed with discrete nodules comprised of small germinal centers, and separated
      by an admixture of lymphocytes, spindled stromal cells, collagen, and blood
      vessels, in which highly atypical tumor cells were embedded. The differential
      diagnosis included Hodgkin's disease, Castleman's disease, and inflammatory
      pseudotumor. Immunohistochemical evaluation revealed a pre-dominance of T cells
      in the lymphocytic population. Molecular genetic studies revealed no evidence of
      clonal rearrangement of the T cell receptor gene, supporting the interpretation
      of these lymphocytes as reactive. Awareness of the existence of this variant of
      inflammatory liposarcoma should prevent its misinterpretation as a primary
      lymphoproliferative process.

PMID- 9255252
TI  - Primitive neuroectodermal tumors arising in testicular germ cell neoplasms.
AB  - Twenty-nine young men (mean age 29 years) had primitive neuroectodermal tumors
      (PNETs) arising in germ cell tumors (GCTs). Nine patients had PNETs confined to
      the testis, eight patients had PNETs in the testis and at metastatic sites, and
      12 patients had PNETs identified only at extratesticular sites.
      Immunohistochemistry was of use in the further classification of these PNETs as
      neuroblastoma, medulloepithelioma, peripheral neuroepithelioma, or
      ependymoblastoma. The histologic pattern of PNETs in the testis (neuroblastoma or
      medulloepithelioma) did not predict which tumors metastasized. PNETs localized to
      the testis did not affect prognosis. Eight patients with no PNETs outside the
      testis were free of disease 1 month to 10 years after diagnosis. PNETs in
      extratesticular sites were an adverse prognostic factor. Nineteen patients with
      extratesticular PNETs had adequate clinical follow-up. Thirteen are dead of
      disease from 4 months to 5 1/2 years (mean 26 months) after diagnosis, four are
      alive with disease 6 months to 2 years after diagnosis, and two have no evidence
      of disease with short follow-up (6 and 17 months). Mean survival was longer (34
      months) for patients whose extratesticular PNET was neuroblastoma than for those
      with other types of PNETs (13 months). Chemotherapy directed against GCTs was not
      effective in patients who developed metastatic PNETs of GCT origin. We conclude
      that extratesticular PNETs in patients with testicular GCTs are usually fatal,
      but patients with neuroblastomatous metastases may have a more prolonged course.

PMID- 9255253
TI  - Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a
      clinicopathologic study of 12 cases.
AB  - Twelve cervical tumors showing morphologic evidence of neuroendocrine
      differentiation and lesional cells larger than those of typical small cell
      carcinoma are reported in women 21 to 62 (mean 34) years of age. The patients
      presented with an abnormal Papanicolaou smear or vaginal bleeding. Two tumors
      were stage Ia2, nine were stage Ib, and one was stage IIa. All patients were
      treated by radical hysterectomy, and most received adjuvant chemotherapy. Seven
      of 10 patients with > 1 year of follow-up died of tumor 6 to 24 months after
      hysterectomy. The tumors had insular, trabecular, glandular, and solid growth
      patterns and contained medium to large cells with moderate to abundant cytoplasm;
      eosinophilic cytoplasmic granules were present in nine cases. The tumors were
      mitotically active, and necrosis was present in 10 of them. Nine of 10 tumors
      were argyrophilic, and all 12 were immunoreactive for chromogranin. Individual
      cells containing somatostatin, serotonin, or glucagon were identified in four of
      eight cases. Adenocarcinoma in situ was present adjacent to the tumor in eight
      cases; invasive adenocarcinoma of non-neuroendocrine type was present in three of
      these tumors. Using diagnostic criteria established for pulmonary neuroendocrine
      tumors, the 12 tumors were classified as large cell neuroendocrine carcinomas.
      Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas
      that are frequently misdiagnosed and have an unfavorable outcome, similar to that
      of small cell carcinoma.

PMID- 9255254
TI  - Papillary squamotransitional cell carcinoma of the cervix: a report of 32 cases.
AB  - Papillary carcinomas of the uterine cervix with transitional or squamous
      differentiation are rare tumors that often resemble transitional cell carcinomas
      of the urinary tract. We reviewed 32 such cases of papillary cervical carcinoma
      and divided them into three groups: 1) predominantly (> 90%) squamous (nine
      cases), 2) mixed squamous and transitional (16 cases), and 3) predominantly
      transitional (seven cases). Overall, the patients ranged in age from 22 to 93
      years (mean 50), and the most common clinical presentation was abnormal bleeding
      (15 patients) and an abnormal Papanicolaou smear (nine patients). The tumors
      ranged in size from 0.7 to 6.0 cm (mean 3.0). All cases demonstrated a papillary
      architecture with fibrovascular cores lined by a multilayered, atypical
      epithelium resembling a high-grade squamous intraepithelial lesion of the cervix.
      Underlying superficial to deep stromal invasion was seen in 18 of 20 cases (90%);
      in the remaining 12 cases, the specimen was too superficial to assess invasion.
      Eighteen (86%) of the 21 cases examined immunohistochemically demonstrated
      immunoreactivity for cytokeratin 7, whereas only two of the 21 (9.5%) showed
      positivity for cytokeratin 20. Of the 12 women for whom follow-up information was
      available, three were treated by simple hysterectomy, two underwent radical
      hysterectomy, one was treated with radiation alone, and one with combination
      chemotherapy and radiotherapy. Three patients died of disease (two in the
      squamous group and one transitional) within an average of 13 months after
      diagnosis. Local recurrence developed in two women, and one of these, a vaginal
      recurrence, occurred 12 years after the original diagnosis. Based on the above
      findings, we believe that these tumors are a clinicopathologically distinct,
      homogeneous group that display a morphologic spectrum. Nevertheless, because some
      tumors may show a purely squamous or purely transitional appearance, we propose
      retaining the above three separate designations for these tumors with the
      understanding that there is often a substantial degree of subjectivity in
      deciding whether a tumor is squamous or transitional. The most distinctive,
      objective, and easily recognizable feature of these tumors is their surface
      papillary architecture rather than their superficial resemblance to transitional
      cell carcinomas of the urinary tract, and we emphasize the need to distinguish
      these potentially aggressive malignant tumors from the far more common and benign
      papillary lesions of the cervix.

PMID- 9255255
TI  - Antimitochondrial antibody (113-1) in the differential diagnosis of granular
      renal cell tumors.
AB  - Abundant granular eosinophilic cytoplasm is a common feature of renal oncocytoma,
      chromophobe renal cell carcinoma, eosinophilic variant of papillary renal cell
      carcinoma, and the granular variant of clear cell renal cell carcinoma (RCC).
      Each of these entities has a unique architectural pattern and a distinctive
      molecular or cytogenetic profile. The chief reason for their distinction from one
      another is the difference in their biologic behavior. Careful and thorough light
      microscopic examination distinguishes most cases based on individual
      characteristic architectural and cytomorphologic features. However, precise
      characterization may be difficult in some cases because of overlapping
      morphologic features. We evaluated the antimitochondrial antibody 113-1 in an
      attempt to ascertain differences in immunostaining patterns in 57 cases of
      granular renal tumors, including 20 renal oncocytomas, 15 chromophobe RCCs, 13
      granular variants of clear cell RCC, and nine eosinophilic variants of papillary
      RCC. Distinctive, and nearly exclusive, staining patterns were observed among the
      groups, with chromophobe RCC showing peripheral accentuation of coarse
      cytoplasmic granules (15 of 15), renal oncocytoma with diffuse and fine
      granularity (20 of 20), and granular variant of clear cell RCC with irregular
      cytoplasmic distribution of coarse granules (11 of 13). Staining was most intense
      in the eosinophilic variant of papillary RCC and was generally coarsely granular
      and diffuse. Staining patterns also differed in clear cell areas within
      chromophobe RCC and the granular variant of clear cell RCC. Although clear cells
      in the former group showed granular staining with peripheral accentuation, most
      of the clear cells in the latter lacked any staining. We conclude that, in
      addition to distinct cytoarchitectural features, immunostaining patterns with
      antimitochondrial antibody 113-1 appear to be a useful discriminatory adjunct in
      the complex differential diagnosis of granular renal cell tumors.

PMID- 9255256
TI  - Prostatic adenocarcinoma with atrophic features: malignancy mimicking a benign
      process.
AB  - Acinar atrophy and postatrophic hyperplasia in the prostate are commonly confused
      with adenocarcinoma. The converse situation may also present a diagnostic
      dilemma. We recently encountered a number of cases of adenocarcinoma with
      features that mimicked atrophy, raising the serious concern for the
      underdiagnosis of malignancy. To investigate the frequency of prostatic
      adenocarcinoma with atrophic features and the histologic criteria that allow its
      distinction from benign processes, we reviewed the histopathologic findings in
      202 consecutive totally embedded whole-mount radical prostatectomy specimens with
      adenocarcinoma, 100 consecutive routine needle biopsy specimens, and five
      additional selected needle biopsy specimens. None of the patients had received
      androgen deprivation therapy before specimen acquisition. Prostatic
      adenocarcinoma with atrophic features was defined as a proliferation of malignant
      acini that architecturally resembled atrophy or postatrophic hyperplasia but
      retained the diagnostic cytologic features of cancer. The acini were round, often
      dilated and distorted, and lined by flattened attenuated epithelium with scant
      cytoplasm. All cases had cytologic evidence of malignancy, including nuclear
      enlargement and prominent nucleoli; these findings could not be attributed to
      inflammation or treatment effect. Atrophic features were identified in cancer in
      six radical prostatectomy specimens (3%) and two routine needle biopsy specimens
      (2%). The proportion of cancer with atrophic features comprised a mean of 27% of
      each tumor in the prostatectomy specimens (range 10-60%) and 24% in the needle
      biopsies (range 10-90%). In the prostatectomy cases, the Gleason score of the
      cancers was 7 (in five cases) and 5 (in one case); in the biopsy specimens the
      Gleason score was 6 (in five cases) and 7 (in two cases). In addition, atrophic
      cancer in the prostatectomy cases had luminal eosinophilic proteinaceous
      secretions (six cases), blue mucin (five cases), crystalloids (two cases),
      apocrine blebs (three cases), collagenous micronodules (one case), and high-grade
      prostatic intraepithelial neoplasia within two high-power fields (three cases);
      the histologic features were similar in the needle biopsy specimens. We conclude
      that prostatic adenocarcinoma with atrophic features is an unusual finding that
      is easily confused with benign acinar atrophy. It is recognized by a combination
      of architectural and cytologic findings and usually coexists with typical Gleason
      score 5-7 acinar adenocarcinoma. This pattern is important to recognize to avoid
      the underdiagnosis of malignancy.

PMID- 9255257
TI  - Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5
      immunoreactivity.
AB  - Thus far, there are no immunohistochemical markers that are specific for thymic
      epithelial neoplasms, although demonstration of immature T cells in an epithelial
      tumor can indirectly support a diagnosis of thymoma. In this study, the
      usefulness of a paraffin section-reactive CD5 antibody (clone CD5/54/B4) for
      supporting the thymic origin of an epithelial neoplasm was evaluated. Antigen
      retrieval was effected by microwaving in citrate buffer. Sixteen of 24 thymic
      carcinomas (67%) were immunoreactive for CD5, including nine of nine squamous
      cell, two of two undifferentiated, two of four lymphoepithelioma-like, and one
      case each of basolid carcinoma, clear cell carcinoma, and unclassified thymic
      carcinoma, but none of four thymic small cell carcinomas. None of 17 cases of
      benign thymoma and 21 cases of invasive thymoma (including six cases classifiable
      as well-differentiated thymic carcinoma using the Muller-Hermelink criteria) was
      immunoreactive for CD5, in the presence of CD5-positive lymphocytes as an
      internal positive control. Two of three thymic neoplasms with features borderline
      between thymic carcinoma and invasive thymoma were immunoreactive for CD5. In
      contrast, none of 61 cases of other malignant neoplasms with a tendency to
      involve the mediastinum was immunoreactive for CD5, including 40 nonthymic
      carcinomas and 13 malignant germ cell neoplasma. CD5 staining of thymic
      epithelial tumors correlated with the absence of tumor-associated CD99-positive
      thymocytes, as demonstrated in our previous studies. We conclude that CD5 is a
      useful marker of primary thymic carcinomas. Taken together, CD5 and CD99 (or
      other immature T-cell markers such as TdT and Cd1a) should be particularly useful
      in evaluating mediastinal and other biopsy samples of possible thymic epithelial
      neoplasms and in the subtyping of these tumors.

PMID- 9255259
TI  - Granulomatous epididymal lesion of possible ischemic origin.
AB  - In a histologic review of adult epididymides obtained at autopsy (both
      epididymides of 408 men) or during surgery (261 men with testicular or epididymal
      nontumoral pathology), a peculiar granulomatous lesion was observed in two
      autopsy specimens (unilateral) and three surgical specimens. The lesion was
      located in the caput epididymidis and consisted of a zone of necrosis that
      involved efferent ducts and interstitial connective tissue and was not associated
      with an acute inflammatory response. Immunohistochemical study with
      anticytokeratin antibodies showed the presence of some epithelial cells in the
      damaged efferent ducts. At the periphery of the lesion, where damage was less
      severe, the efferent ducts only showed partial necrosis of their wall through
      which the necrotic material was released to the ductal lumen. Inflammatory
      infiltrates were scanty and consisted of lymphocytes and CD68-positive
      macrophages. Lymphocytes were mainly located around the necrotic zone or
      surrounding the adjacent, well-preserved efferent ducts, whereas macrophages
      formed large clusters in the ductal lumen. In these clusters, cholesterol
      crystals and giant cells of foreign body type were frequent. Intratubular
      epithelial regeneration as well as proliferation of small ducts showing
      epithelial regeneration and numerous spermatozoa in their lumen were observed.
      Ceroid granulomata, spermatic granulomata, and epidermoid metaplasia of the
      efferent ducts were observed in some cases. On the basis of the histologic study,
      the following developmental stages of the lesion are suggested: ischemic
      necrosis, granulomatous reaction, cicatrization, and sequelae. The term
      "granulomatous ischemic lesion" is proposed to designate this reactive lesion.

PMID- 9255260
TI  - Cytogenetic and immunohistochemical analysis of an adult anaplastic
      neuroblastoma.
AB  - Neuroblastomas in children are common tumors and are characterized by a number of
      recurrent cytogenetic and molecular changes. Adult neuroblastomas are rare, and
      their relationship to pediatric neuroblastomas is not clear. We report an
      anaplastic neuroblastoma presenting in a 28-year-old man. Histopathologic
      identification of the tumor as a neuroblastoma was problematic, and the initial
      diagnosis was poorly differentiated sarcoma. Tumor cells expressed
      immunoreactivity for tyrosine hydroxylase in addition to generic neuroendocrine
      markers, consistent with catecholamine-synthesizing ability. They also extended
      long, branching neurites in vitro. The tumor was positive for immunoreactive
      trkA. The karyotype after 6 days in culture was found to be 42,XY with multiple
      chromosomal abnormalities. The only abnormality shared with pediatric
      neuroblastomas was a rearrangement of chromosome 17q. Double minute chromosomes
      or homogeneously staining regions associated with N-myc amplification were not
      present. To our knowledge, this is the first reported karyotype of an adult
      neuroblastoma. The cytogenetic findings, together with expression of trkA,
      suggest that the tumor was more closely related to the favorable prognosis
      neuroblastomas of infancy than to the poor prognosis tumors that occur in older
      children, despite its unfavorable histology.

PMID- 9255258
TI  - Expression of vascular endothelial growth factor and its receptors in pilocytic
      astrocytoma.
AB  - Vascular endothelial growth factor (VEGF), a potent angiogenic and vascular
      permeability factor, is important in the angiogenesis of glioblastoma. A major
      difference between pilocytic astrocytoma, a grade I tumor, and the grade II
      fibrillary astrocytoma is the vascular proliferation, highly vascularized stroma,
      and great propensity for cyst formation in the former. In order to explore
      factors regulating such angiogenesis and cyst formation in pilocytic astrocytoma,
      we examined expression of VEGF and its receptors (KDR and Flt-1) using in situ
      hybridization. In all 14 cases a high level of VEGF transcripts could be
      demonstrated. These were found in specific regions, namely, in the tumor cyst
      wall, in areas of hyaline cystic degeneration, in stellate reticulated astrocytes
      around microcysts in the biphasic compact and loose areas, and in tumor cells
      with degenerative pleomorphic multicoated nuclei. KDR and Flt-1 were expressed in
      the tumor vasculature, with particularly high levels seen in coiled young
      proliferating vessels, especially those in the cyst wall. Given the known
      angiogenic and vascular permeability activities of VEGF, we propose that VEGF
      plays an important role in molding the characteristic morphologic features of
      this tumor, namely, the formation of cysts, microcystic pattern, hyaline cystic
      degeneration, hyaline vessels, and vascular proliferation. Mechanisms that block
      the VEGF pathway could constitute a potential therapeutic strategy for the
      treatment of this tumor.

PMID- 9255261
TI  - Natural killer-like T-cell lymphoma in the small intestine of a child without
      evidence of enteropathy.
AB  - A previously healthy 6-year-old boy developed symptoms of small intestinal
      obstruction and was found to have a large intraabdominal mass. At laparotomy the
      mass involved the jejunum and adjacent mesenteric lymph nodes, requiring
      resection. Microscopic and immunohistochemical studies demonstrated a T-cell non
      Hodgkin's lymphoma, confirmed by finding clonal T-cell receptor-beta and -gamma
      gene rearrangements by Southern blot analysis. The immunophenotype of this
      lymphoma-CD3+CD4-CD8-CD56+TIA-1+ beta F1(-)-suggests that the tumor cells are
      cytotoxic natural killer (NK)-like T cells, probably of CD3+CD4-CD8-
      intraepithelial cell origin. Examination of the adjacent and distal small
      intestinal mucosa failed to show any significant pathologic change. This case was
      unusual because intestinal lymphomas in children are usually of B-cell origin and
      most commonly have small noncleaved cell morphology. Childhood intestinal T-cell
      lymphomas have not been the focus of specific study but appear to be rare. In
      adults, intestinal T-cell lymphomas often arise in the background of gluten
      sensitive enteropathy (celiac disease). In contrast, this child had peripheral T
      cell lymphoma, with NK-like T-cell features, in the small intestine with no
      clinical or histologic evidence of enteropathy.

PMID- 9255262
TI  - Metastatic adenocarcinoma involving a mesothelial/monocytic incidental cardiac
      excrescence (cardiac MICE)
AB  - Mesothelial/monocytic incidental cardiac excrescence (MICE) is a recently
      described, peculiar microscopic finding in the endocardium or pericardium. These
      lesions are characterized by a mixture of mesothelial cell clusters and
      histiocytes, aggregated by fibrin. They have been interpreted as reactive or even
      artifactual, and the importance of distinguishing these aggregations from
      metastatic carcinoma has been emphasized. We report a unique case of a MICE that
      was seeded by clusters of metastatic adenocarcinoma cells. The patient was a 38
      year-old woman with no history of previous cardiac instrumentation who was found
      to have an adenocarcinoma of the right lung involving the hilus but apparently
      not invading the pericardium. At surgery, a small fragment of tissue was found
      floating in the pericardial cavity, and microscopic examination revealed a
      cluster of histiocytes, mesothelial cells and fibrin (components of usual, benign
      MICE) in which rare pleomorphic adenocarcinoma cells were scattered. Unlike the
      surrounding mesothelial cells and histiocytes, the pleomorphic cells stained for
      carcinoembryonic antigen, epithelial membrane antigen, and BerEP4 and focally
      produced intracellular mucin, confirming their malignant glandular nature. It is
      possible that the surrounding mesothelial cells, histiocytes, and fibrin were
      formed in response to invasion of the pericardial space by adenocarcinoma. This
      case indicates that not all lesions with the characteristic architecture of MICE
      can be dismissed as non-neoplastic without careful evaluation of both the
      cellular constituents and the clinical circumstances.

PMID- 9255263
TI  - Metastasizing dermatofibroma.

PMID- 9255264
TI  - A guideline for reporting results of statistical analysis in Japanese Journal of
      Clinical Oncology.
AB  - The paper gives guidelines to authors on the use of statistics, including
      statistical considerations when designing studies. Information on this article
      plus a list of other recommended books is available on the World Wide Web
      (http:/(/)wwwinfo.ncc.go.jp/jjco/) in Japanese as well as English.

PMID- 9255265
TI  - A nationwide clinical survey of patients with multiple endocrine neoplasia type 2
      and familial medullary thyroid carcinoma in Japan.
AB  - MEN (multiple endocrine neoplasia) type 2 syndrome is an inherited disease
      characterized by medullary thyroid carcinoma, pheochromocytoma,
      hyperparathyroidism and/or developmental anomalies. Germ-line mutations of the
      RET proto-oncogene have recently been identified as the underlying cause of the
      syndrome. Accordingly, several investigators have advocated prophylactic total
      thyroidectomy for medullary thyroid carcinoma at an early age in MEN 2 gene
      carriers identified by DNA analysis. Before applying this strategy in Japan, the
      biological behavior of each category of tumor in MEN 2 syndrome, and medullary
      thyroid carcinoma in particular, should be well understood. We conducted a
      nationwide questionnaire survey to clarify the clinicopathological features of
      MEN 2 in Japan, obtaining data for 230 patients diagnosed as having MEN 2. They
      included 84 males and 146 females, with a median age of 37.5 years (range 5-83).
      Patients were categorized as 179 with MEN 2A, 17 with MEN 2B, 12 with familial
      medullary thyroid carcinoma and 22 'other'. Medullary thyroid carcinoma,
      pheochromocytoma and parathyroid lesions occurred in 224 (97%), 132 (57%) and 25
      (11%) patients respectively. Twelve patients (5.2%) died of medullary thyroid
      carcinoma and 11 patients died of other or unknown causes. Of 163 patients for
      whom follow-up data were obtained, 82 (50%) experienced recurrences of medullary
      thyroid carcinoma, including symptomatic recurrent tumors in 24 patients and
      elevated calcitonin levels alone in 54. In the era of RET mutational analysis for
      screening relatives of patients with MEN 2, these data provide useful information
      about surgical management for patients with MEN 2 in Japan.

PMID- 9255266
TI  - Increased level of circulating adhesion molecules in the sera of breast cancer
      patients with distant metastases.
AB  - The adhesion of circulating cancer cells to the vascular endothelium is an
      important at step in the hematogenous metastasis of cancer. E-selectin expressed
      on endothelial cells and carbohydrate ligands expressed on cancer cells mediate
      this adhesion. We investigated the clinical significance of such cell adhesion
      molecules in breast cancer. The cytosol concentration of sialyl Lewis(x) was
      found more elevated in cancerous tissue than that in adjacent non-cancerous
      tissue. In the serum, sialyl Lewis(x) and soluble E-selectin were seen elevated
      in patients with advanced and recurrent breast cancer, especially in those with
      distant metastases. From the above, we have concluded that sialyl Lewis(x) and
      soluble E-selectin could be used as tumor markers with a close relationship to
      the metastasis of breast cancer.

PMID- 9255267
TI  - Estimation of adult T-cell leukemia incidence in Kyushu District from vital
      statistics Japan between 1983 and 1982: comparison with a nationwide survey.
AB  - To investigate the change in adult T-cell leukemia incidence between 1983 and
      1992 and to evaluate the sensitivity of the nationwide adult T-cell leukemia
      survey, we estimated adult T-cell leukemia incidence in the Kyushu district,
      southern Japan, where adult T-cell leukemia is endemic. The incidence of adult T
      cell leukemia was calculated from the difference between Kyushu and the rest of
      Japan in mortality from malignant lymphoid neoplasms, i.e., Kyushu's excess rate
      was assumed to be due to adult T-cell leukemia. In Kyushu, average annual adult T
      cell leukemia cases aged > or = 20 years were estimated for men as 252 during the
      period 1983-87 and 341 during 1988-92, and for women as 201 and 246 respectively.
      The age-adjusted mortality rate tended to be higher in the latter period [6.29
      per 100000 (95% confidence interval 5.59-7.00) vs. 5.25 (4.60-5.90) in men, and
      3.33 (2.85-3.80) vs. 3.18 (2.71-3.66) in women]. By contrast, the registered
      number of adult T-cell leukemia cases nationwide during 1988-93 was only 35%
      (203/587) of the estimated number, and the number of registered versus estimated
      cases decreased with age, especially when cases were > 60 years old. In
      conclusion, the estimated adult T-cell leukemia incidence for 1983-92 increased
      in the latter half of the period. The estimation suggests that 65% of adult T
      cell leukemia cases might be missed by a nationwide survey, and older cases were
      more likely than younger ones to be missed.

PMID- 9255269
TI  - High-dose cytarabine and mitoxantrone as salvage therapy for refractory non
      Hodgkin's lymphoma.
AB  - High-dose cytarabine alone or in combination with mitoxantrone has been shown to
      be active against refractory non-Hodgkin's lymphoma in therapeutic trials. We
      administered these two drugs to 16 patients with advanced and refractory non
      Hodgkin's lymphoma. Cytarabine was administered at 3 g/m2 as a 2-h intravenous
      infusion every 12 h on days 1-4 (8 doses) and mitoxantrone at 6 mg/m2/day as a 1
      h intravenous infusion on days 1-5. The clinical efficacy and toxicity were
      assessed according to the WHO criteria. Five patients (31%, 95% CI: 8-54%)
      attained complete remission and two had partial remission. In three of the five
      complete remission patients, the remission lasted for > 4 months. The remaining
      two patients had complete remission for only 1.3 months. Myelosuppression with
      subsequent infection was the major toxicity of this regimen. Severe leukopenia
      (WBC < 1000/microliter) lasted for an average of 20 days and thrombocytopenia (<
      25000/microliter) 18 days. Five patients (31%) died of treatment-related
      complications: neutropenia-associated sepsis in three, pneumonia in one and
      electrolyte imbalance in one. Nonmyeloid toxicities included alopecia in 100%
      (19% Gr.2, 75% Gr.3), stomatitis in 88% (13% Gr.2, 31% Gr.3), hepatotoxicity in
      38% (6% Gr.2, 6% Gr.3), dermatitis in 31% (19% Gr.2), CNS toxicity in 25% (6%
      Gr.2, 6% Gr.3), infection in 38% (13% Gr.3, 19% Gr.4) and chemical conjunctivitis
      in 6% (Gr.2). We conclude that a proportion of refractory non-Hodgkin's lymphoma
      cases will respond to high-dose cytarabine+mitoxantrone, but that the treatment
      seems too toxic to be acceptable as salvage therapy for refractory non-Hodgkin's
      lymphoma.

PMID- 9255268
TI  - Phase I study of cladribine (2-chlorodeoxyadenosine) in lymphoid malignancies.
      Cladribine Study Group.
AB  - Cladribine (2-chlorodeoxyadenosine;) is a purine analogue with clinical activity
      against hairy cell leukemia, chronic lymphocytic leukemia and indolent lymphoma.
      To clarify the toxicity profiles of cladribine, we conducted a phase I and
      pharmacological study of cladribine with a schedule of seven-day continuous
      intravenous infusion every 28 days up to a maximum of three cycles. We enrolled
      10 previously-treated patients with various lymphoid malignancies. No dose
      limiting toxicity (grade 4 hematologic and/or grade 3 or more non-hematologic)
      was observed in the three patients who received 0.06 mg/kg/day (Level 1). Of the
      seven patients who received 0.09 mg/kg/day (Level 2), one patient developed grade
      4 hypoxemia and grade 4 thrombocytopenia, and another developed grade 4
      neutropenia. Of the seven patients treated at Level 2, one with cutaneous T-cell
      lymphoma attained complete remission, and one with mantle cell lymphoma, one with
      chronic lymphocytic leukemia and one with adult T-cell leukemia-lymphoma attained
      partial remission. A pharmacokinetic analysis of the seven patients without
      leukemic cells showed that their area under the concentration versus time curves
      of plasma cladribine increased dose-dependently from 2661.3 +/- 300.4 nM x h at
      Level 1 (n = 3) to 3411.3 +/- 341.0 nM x h at Level 2 (n = 4) (P = 0.034). We
      conclude that the recommended phase II dose of cladribine (0.09 mg/kg/day as a
      seven-day continuous i.v. infusion) in Caucasian patients can be safely
      administered to Japanese patients. The encouraging results prompted us to plan
      subsequent phase II studies of cladribine against adult T-cell leukemia-lymphoma,
      hairy cell leukemia and indolent lymphoma.

PMID- 9255270
TI  - Prognostic factors and prognostic staging system for small cell lung cancer.
AB  - This study was performed to assess the prognostic factors and the predictors of
      long-term (3-year) survival in patients with small cell carcinoma of the lung,
      accrued in one randomized trial, and to define patient subgroups showing
      significantly different survivals using recursive partitioning and amalgamation
      analysis. A total of 300 patients with small cell carcinoma of the lung were
      entered into a randomized study comparing cyclophosphamide, adriamycin and
      vincristine (CAV), cisplatin and etoposide (PE) and alternating treatments of CAV
      and PE. Of these, 286 patients were analysed for the present study of prognostic
      factors. Multivariate analysis showed that poor performance status (2-3) (P =
      0.0001), extensive disease (P = 0.0015) and abnormally elevated serum lactate
      dehydrogenase (P = 0.0001) and alkaline phosphatase (P = 0.0013) were
      independently adverse pretreatment prognostic factors. Of limited disease
      patients, performance status (P = 0.029) and white blood cell count (P = 0.044)
      had a significant influence on the probability of 3-year disease-free survival.
      Using recursive partitioning and amalgamation analysis, three classes of similar
      prognosis were identified: the most favorable class was defined by knowledge of
      lactate dehydrogenase (normal), performance status (0-1) and serum sodium levels
      (normal) with median survival time of 16.0 months, and the class with the poorest
      prognosis was defined by knowledge of lactate dehydrogenase (elevated) and
      performance status (2-3) (median survival time 6.6 months). The intermediate
      class had a median survival time of 9.4 months. In conclusion, this
      subclassification system will be used for the design, implementation and
      interpretation of clinical studies as well as decision-making in individual
      patients.

PMID- 9255271
TI  - Second-line chemotherapy for relapsed small cell lung cancer.
AB  - Between January 1985 and August 1991, 159 patients with small cell lung cancer
      received first-line chemotherapy and 123 (77%) were responders. Of these, 88
      relapsed, the remainder having died of other or unknown diseases or being alive
      without carrying cancer. The relapsed patients were examined to evaluate the
      outcome of the treatment for relapsed small cell lung cancer and to identify the
      factors that would contribute to the response rates and the survival durations.
      Forty-eight of 88 relapsed patients received second-line chemotherapy. Of the 48,
      3 were evaluated as showing a complete response, 13 as partial response, 9 as no
      change, 15 as progressive disease and 8 as not evaluable. The response rate was
      33% (95% confidence interval 20.4-48.4%). The median survival time was 146 days.
      The duration and rate of response in first-line chemotherapy affected the
      response rates of the second-line chemotherapy, but without statistical
      significance (P = 0.058 and 0.067 respectively). Increased response duration,
      time off chemotherapy and previous response to first-line chemotherapy all had a
      positive effect on the survival times (P < 0.01). Relapsed small cell lung cancer
      still shows a response to second-line chemotherapy without lessening survival
      time, and thus clinical trials of new drugs or combination chemotherapeutic
      regimens for relapsed small cell lung cancer cases would be reasonably justified.
      Randomized comparative studies are warranted for determining the benefits of
      second-line chemotherapy for relapsed small cell lung cancer cases.

PMID- 9255272
TI  - Technical considerations for fractionated stereotactic radiotherapy of
      hepatocellular carcinoma.
AB  - Technical aspects of fractionated stereotactic radiotherapy for solitary
      hepatocellular carcinoma have been investigated. Precise positioning of the
      patient and substantial reduction of the liver movement due to respiration were
      achieved by placing the patient ventrally on the treatment couch without a body
      cast. Repeated CT examinations were required for verification of tumor targeting.
      Though there were geometrical limitations on gantry rotation when the linac couch
      was rotated from its standard position, dose distributions obtained were found to
      be excellent. A patient with a small solitary lesion in the posterior segment of
      the liver received 52 Gy in 13 fractions over 29 days. He tolerated the treatment
      well without experiencing any morbidities or deterioration of liver functions.
      Three months later his alpha-fetoprotein value returned to normal and CT
      examinations revealed tumor shrinkage as well as a reduction in the viability of
      the tumor cells. The results suggest that it is possible to overcome technical
      difficulties associated with fractionated stereotactic radiotherapy of
      intraabdominal tumors.

PMID- 9255273
TI  - Factors predictive of response and survival in patients with metastatic
      colorectal cancer in Taiwan.
AB  - 5-Fluorouracil in combination with leucovorin has been shown to be active in
      therapeutic trials of metastatic colorectal carcinoma. In this study, we
      administered these drugs to 72 patients with metastatic colorectal carcinoma.
      Thirty-six of them without previous exposure to 5-fluorouracil were treated with
      weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2)
      supplemented with oral levamisole. Another 36 patients with or without prior 5
      fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300
      mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and
      toxicity were assessed by WHO criteria. Variables were tested for relations to
      response and survival by univariate and multivariate analysis. The response rate
      was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P =
      0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months
      (biweekly) respectively (P = 0.708). Gastrointestinal side effects including
      nausea, vomiting, diarrhea and mucositia were the major toxicities of these
      regimens. By multivariate analysis, the only factor to influence response rate
      was the site of metastases (P = 0.009). The only factor to affect survival was
      performance status of the patient (P = 0.0001). We concluded that the two 5
      fluorouracil based regimens are well-tolerated and shown to have a response rate
      comparable with previous reports of similar regimens in patients with metastatic
      colorectal cancer. Only liver metastases seemed to have a better response to
      therapy. Performance status is the most important prognostic factor in patients
      with metastatic colorectal cancer.

PMID- 9255274
TI  - Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid
      carcinoma.
AB  - A 28-year-old woman was admitted to our Hospital with a chief complaint of
      progressive gingival swelling and loosening of teeth over about a year. According
      to past history, she had received total thyroidectomy 2 years previously due to
      thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly
      differentiated carcinoma of the thyroid'. One year ago, she began to be aware of
      gingival swelling and loosening of teeth. A gum biopsy was taken and the
      pathologic features were similar to her 'thyroid carcinoma'. Subsequent
      investigations, including immunohistochemical stain, showed the gum was heavily
      infiltrated with histiocyte-like Langerhans' cells which were positive for S-100
      protein. Ultrastructural examination of the cells under electron microscope
      revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell
      histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid
      involvement is extremely rare and may run a relatively indolent course. Even on a
      retrospective examination, it may easily be confused with poorly differentiated
      carcinoma of the thyroid. We suspect that this error may have been made on other
      occasions and that the occurrence of this condition may be underreported.

PMID- 9255275
TI  - Intersegmental attenuation difference on CT caused by partial Budd-Chiari
      syndrome secondary to hepatocellular carcinoma: report of two cases.
AB  - For two patients with partial Budd-Chiari syndrome secondary to hepatocellular
      carcinoma, dynamic CT was evaluated. The obstructed hepatic veins were both the
      middle and left hepatic veins in Case 1 and the right hepatic vein in Case 2. The
      area affected by obstructed hepatic vein(s) was seen as low density on both
      unenhanced and contrast enhanced CT in Case 1 and as high density on enhanced CT
      in Case 2. The border of attenuation differences caused by the obstruction of the
      middle (Case 1) or right (Case 2) hepatic vein was intersegmental planes of the
      anterior segment of the right lobe, and that caused by the obstruction of the
      left hepatic vein was the intersegmental plane of the medial third of the left
      lateral segment. Once intersegmental attenuation difference is recognized on CT,
      partial Budd-Chiari syndrome should be considered.

PMID- 9255276
TI  - A case of liver metastasis from colon cancer masquerading as focal sparing in a
      fatty liver.
AB  - Focal sparing in diffusely fatty liver is a well recognized entity. However, it
      occasionally creates some problems in the diagnosis of hepatic mass lesions. We
      recently experienced a case of liver metastasis from colon cancer which appeared
      as a wedge-shaped hyperdense area on non-enhanced CT (computed tomography). Other
      imaging techniques also demonstrated a wedge-shaped area which was difficult to
      distinguish from mere focal sparing in the fatty liver. CT arteriography and
      dynamic magnetic resonance images were useful for diagnosing this metastatic
      tumor. CT during arterial portography showed a wedge-shaped ischemic area in the
      anterior segment caused by intrahepatic portal vein blockade. The histological
      findings eventually revealed that the tumor, an adenocarcinoma, was surrounded by
      fibrotic tissue that mimicked focal sparing. We present the radiological features
      of this case and discuss how to arrive at a correct diagnosis.

PMID- 9255278
TI  - Sclerosing sweat duct carcinoma in the peri-anal skin: a case report.
AB  - We report a case of sclerosing sweat duct carcinoma, a rare tumor, occurring in
      the peri-anal skin, a rare position. The patient, a 41-year-old Japanese woman,
      was admitted to our hospital with recurrence of sclerosing sweat duct carcinoma
      in the peri-anal skin, which had been initially resected at a local hospital. She
      underwent abdomino-perineal resection. No lymph node metastases or distant
      metastases were found. Although we allowed a 2-cm resection margin around the
      tumor, microscopy showed that the tumor had extended to within 2 mm of this
      margin at several sites, indicating that sclerosing sweat duct carcinoma is
      locally aggressive. An ample resection margin should therefore be taken at
      initial surgery for this type of tumor. Moreover, surgical excision that is wider
      and deeper than primary excision is required when this tumor recurs.

PMID- 9255277
TI  - Papillary adenocarcinoma of the sigmoid colon associated with psammoma bodies and
      hyaline globules: report of a case.
AB  - We report a case of papillary adenocarcinoma of the sigmoid colon with psammoma
      bodies and intracytoplasmic hyaline globules. The patient was a 59-year-old
      woman. The tumor showed central ulceration with smooth elevated ridges.
      Histologically, the tumor was composed of numerous large irregular tubular
      structures accompanying infolded papillary growth. The tumor cells showed
      cytoplasmic basophilia and prominent nuclear atypia. Psammomatous-type
      calcification was scattered in the tumor stroma as well as in the glandular
      lumina. In addition, intracytoplasmic hyaline globules of various sizes were seen
      in the neoplastic cells. We propose the name papillary adenocarcinoma associated
      with psammoma bodies and hyaline globules for this tumor. Accumulation of further
      cases is needed to clarify the clinical significance of this type of tumor.

PMID- 9255279
TI  - Superficial angiomyxoma of the right inguinal region: report of a case.
AB  - We report one rare case of superficial angiomyxoma of the right inguinal region,
      in a 67-year-old man. The tumor, measuring 4.5 x 4.0 x 3.0 cm, had a finger-like
      shape, was composed of a well circumscribed conglomerate of multiple myxomatous
      nodules and was located partially in the dermis and partially in the subcutaneous
      tissue. Microscopically, in contrast to previously reported cases, the tumor was
      composed mainly of oval plump stromal cells with an amphophilic cytoplasm.
      Spindle-shaped stromal cells were scattered throughout the tumor. The tumor
      border was not infiltrative and was well defined by thick hyalized collagen
      bundles. Neither hyperchromasia nor pleomorphism was apparent. No mitotic figures
      were detected in the specimens prepared. Small to medium-sized blood vessels
      showed a scattered distribution, but large vessels, seen frequently in aggressive
      angiomyxoma, were absent. Moreover, no plexiform capillary pattern was evident.
      These findings were diagnostic of superficial angiomyxoma. Although this disease
      entity is considered as including cutaneous focal mucinosis, follicular fibroma,
      trichofolliculoma and trichogenic adnexal tumor, we propose that these tumors
      should be excluded.

PMID- 9255280
TI  - CT-guided bronchoscopic barium marking for resection of a fluoroscopically
      invisible peripheral pulmonary lesion.

PMID- 9255281
TI  - Gastric cancer staging in Japan: a comparison with British practice.

PMID- 9255282
TI  - Transurethral microwave thermotherapy: minimally invasive therapy for benign
      prostatic hyperplasia.

PMID- 9255283
TI  - Transurethral needle ablation of the prostate.

PMID- 9255284
TI  - Glycosaminoglycans and semisynthetic sulfated polysaccharides: an overview of
      their potential application in treatment of patients with urolithiasis.

PMID- 9255285
TI  - Detection of circulating prostate cells by reverse transcriptase-polymerase chain
      reaction of human glandular kallikrein (hK2) and prostate-specific antigen (PSA)
      messages.
AB  - OBJECTIVES: To investigate the clinical value of human glandular kallikrein (hK2)
      reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of
      prostate cells in circulation and to compare the results with those obtained from
      prostate-specific antigen (PSA) RT-PCR. METHODS: We examined peripheral blood
      (PB) and bone marrow (BM) samples of 13 patients with advanced-stage prostate
      cancer and 63 patients with clinically localized disease for the presence of
      circulating prostate cells. An RT-PCR protocol with a two-step amplification
      cycle and hot-start conditions was used. RESULTS: The limit of detection of the
      PCR portion is similar for PSA and hK2 (5 to 10 copies of the plasmid containing
      the cDNA). The RT-PCR limit of detection is one LNCaP cell in 10(8) peripheral
      blood mononuclear cells (PMBC) for PSA, and one LNCaP cell in 10(7) PMBC for hK2.
      Of the BM samples obtained prior to radical prostatectomy, 71.4% were positive
      for PSA mRNA and 41.3% were positive for hK2 mRNA. In PB, the PSA positivity was
      19% and hK2 positivity 12.7%. In advanced-stage patients, there were 76.9% PSA
      positive samples in BM versus 38.5% hK2-positive samples; 46.2% of patients were
      positive in PB for PSA versus 30.8% for hK2. CONCLUSIONS: We have developed a
      sensitive RT-PCR protocol for detection of hK2 mRNA and evaluated the suitability
      of hK2 mRNA in comparison with PSA mRNA as an additional marker for detection of
      prostate cells in circulation. Combining results of these two tests increased the
      sensitivity of detection.

PMID- 9255286
TI  - Urinary nitrite: more than a marker of infection.
AB  - OBJECTIVES: The bacteriostatic gas nitric oxide (NO) is formed when nitrite is
      acidified. Infected urine may contain considerable amounts of nitrite as a result
      of bacterial nitrate reductase activity, and detection of nitrite in urine is
      routinely used in the diagnosis of bacterial cystitis. We sought to determine
      whether NO was generated from acidified nitrite-containing urine. Furthermore, we
      also studied the growth of the urinary pathogen Escherichia coll in acidified
      nitrite-containing urine. METHODS: Urine, collected from healthy control subjects
      or from patients with infected nitrite-containing urine, was acidified and
      incubated in a closed syringe with varying amounts of nitrite added. After 30
      minutes, the headspace gas was removed and immediately injected into a
      chemiluminescence NO analyzer. In addition, NO was measured in urine collected
      from healthy control subjects after ingestion of vitamin C. Bacterial growth was
      measured continuously in control urine for 10 hours after incubation for 2 hours
      in acidic urine with varying concentrations of nitrite added. RESULTS: Large
      amounts of NO were released from infected nitrite-containing urine after mild
      acidification. NO was also released from acidified control urine if nitrite was
      added, and this release was greatly potentiated in the presence of vitamin C.
      Furthermore, the growth of E. coli was markedly reduced by the addition of
      nitrite to acidified urine. CONCLUSIONS: We propose that nitrite-producing
      bacteria induce their own death in acidic urine by supplying substrate for
      generation of bacteriostatic compounds such as NO. This mechanism might explain
      why urinary acidification and vitamin C may be effective in the treatment of
      bacteriuria.

PMID- 9255287
TI  - Incidence of stool guaiac conversion following extracorporeal shock wave
      lithotripsy.
AB  - OBJECTIVES: To study, in a prospective fashion, acute traumatic effects on the
      gastrointestinal tract of patients treated by extracorporeal shock wave
      lithotripsy (ESWL). METHODS: Stool samples from each of 54 patients were tested
      before and after ESWL for conversion to hemoccult positive. A minimum of one
      negative pre-ESWL stool guaiac test was required for inclusion into the study. A
      minimum of two stool guaiac tests were done after ESWL to verify negativity.
      Patients who converted to a positive hemoccult test after ESWL were then
      evaluated by colonoscopy for the source of bleeding. RESULTS: Fifty patients
      completed the study. A single patient (2.0%) converted to a positive post-ESWL
      hemoccult test and was evaluated with colonoscopy. This patient was found to have
      two benign adenomatous polyps in the sigmoid and descending colon after treatment
      for a left renal pelvis calculus. An additional patient with a slightly positive
      post-ESWL conversion refused further evaluation. The overall post-ESWL conversion
      rate to guaiac positive, therefore, was less than 4% (2 of 51 patients).
      CONCLUSIONS: There is no evidence of significant trauma or detectable bleeding in
      the normal gastrointestinal tract caused by ESWL as measured by postprocedure
      stool guaiac testing. Guaiac testing of the stool after ESWL may unmask pre
      existing gastrointestinal disease. Therefore a positive guaiac test after ESWL
      warrants further evaluation. This study reaffirms that ESWL is a safe, minimally
      invasive technique for the treatment of urolithiasis, without significant adverse
      side effects on the gastrointestinal tract.

PMID- 9255288
TI  - Retroperitoneoscopic renal biopsy in extremely obese patients.
AB  - OBJECTIVES: Retroperitoneoscopic renal biopsy can be technically challenging in
      extremely obese patients because of loss of surgical landmarks and difficulty in
      identifying the kidney within retroperitoneal adipose tissue. We present our
      experience with retroperitoneoscopic renal biopsy in extremely obese patients and
      describe our surgical technique. METHODS: We performed retroperitoneoscopic renal
      biopsies on 8 extremely obese patients (body mass index greater than 40). Mean
      patient weight was 144.3 kg. Three patients presented with acute renal failure
      and 5 presented with nephrotic range proteinuria. Retroperitoneoscopic renal
      biopsy was indicated based on extreme obesity alone in 3 patients, 2 patients had
      failed previous attempts at percutaneous biopsy, 1 patient had a solitary kidney,
      1 patient required chronic anticoagulation, and 1 patient was a Jehovah's
      Witness. Intraoperative ultrasonography and an anatomic approach facilitated the
      dissection and identification of the kidney. RESULTS: All eight
      retroperitoneoscopic renal biopsies were completed successfully without
      complication and all patients were discharged within 24 hours of the procedure.
      Sufficient tissue for pathologic diagnosis was obtained in all cases. Mean
      operating room time was 153 minutes and mean estimated blood loss was 71 mL. The
      patients returned to normal activity at a mean of 1.8 weeks. CONCLUSIONS: With
      the use of intraoperative ultrasonography and a systematic, anatomic approach,
      retroperitoneoscopic renal biopsy can be successfully completed in extremely
      obese patients. This procedure can be reliably performed on an outpatient basis
      with minimal morbidity and should be considered a viable alternative to open
      renal biopsy.

PMID- 9255289
TI  - Phase I trial of photodynamic therapy in the treatment of recurrent superficial
      transitional cell carcinoma of the bladder.
AB  - OBJECTIVES: A Phase I trial of photodynamic therapy (PDT) in the treatment of
      superficial transitional cell carcinoma (TCC) of the bladder was performed.
      METHODS: Twenty patients with recurrent superficial TCC of the bladder after
      receiving a mean of 2.6 (range 1 to 6) courses of intravesical therapy were
      treated with PDT. The photosensitizer Photofrin II dose was 1.5 or 2.0 mg/kg. A
      630-nm intravesical red laser was used to activate the photosensitizer 2 days
      after administration of Photofrin II. A 0.01% intralipid solution was used as a
      bladder-filling medium to scatter light and achieve more homogeneous light
      distribution. Light doses from 5.1 to 25.6 J/cm2 (total dosage 1500 to 5032 J)
      were used to illuminate the bladder. RESULTS: Twenty patients underwent 21
      treatments with PDT. Complications included asymptomatic reflux in 4 patients.
      One other patient, treated at the highest total light dose, experienced bladder
      contraction and fibrosis. Nine patients (45%) had no tumor evident at cystoscopy,
      on random biopsies, or in urinary cytology at the 3-month evaluation after
      treatment. Four patients remained without recurrent disease for 23 to 56 months.
      Sixteen of 20 (80%) patients experienced recurrence, and 8 of the 16 underwent
      cystectomy. CONCLUSIONS: An intravenous photosensitizer dose of 1.5 mg/kg
      Photofrin II followed by light energy in the range of 13 J/cm2 (total light dose
      2500 to 3250 J) was defined as a safe treatment parameter and resulted in tumor
      responses. With present technologies, administration of PDT requires careful
      dosimetry.

PMID- 9255290
TI  - Twenty-year experience with jejunal conduits.
AB  - OBJECTIVES: To assess the results of jejunal conduit urinary diversion, with
      particular attention to electrolyte imbalance and long-term renal function.
      METHODS: From 1976 to 1994, 50 patients underwent urinary diversion using a short
      jejunal loop (10 to 12 cm) placed transperitoneally. Of these patients, 18
      received pelvic irradiation before diversion. Renal function and configuration of
      the upper urinary tract were assessed by creatinine clearance and excretory
      urography. RESULTS: Median follow-up was 26 months (3 to 204). Of 50 patients, 22
      had a follow-up more than 5 years later (median 86 months). Eight patients (16%)
      underwent 10 revision procedures postoperatively. Late complications related to
      urinary diversion included renal calculi (12%), parastomal hernia (6%),
      pyelonephritis (4%), ureterojejunal obstruction (4%), and stomal prolapse (2%).
      Electrolyte imbalance occurred in 2 patients (4%) and was easily corrected by 4 g
      sodium bicarbonate. No significant decrease in creatinine clearance (P = 0.6) was
      found in 22 patients with a follow-up of more than 5 years; however, of these
      patients, 2 had a decrease in creatinine clearance of greater than 20%, due to
      ureterojejunal obstruction. Of 42 ureterorenal units, hydronephrosis occurred and
      increased in 1 and 2 cases, respectively, and renal scarring occurred and
      progressed in 2 and 2 cases, respectively. CONCLUSIONS: Urinary diversion using a
      short length of jejunum placed transperitoneally is a reliable procedure and
      gives good long-term renal function. Electrolyte imbalances are rare. Moreover,
      jejunal conduit can be used in almost all situations, especially after pelvic
      irradiation.

PMID- 9255291
TI  - Benign prostatic hyperplasia in Sweden 1987 to 1994: changing patterns of
      treatment, changing patterns of costs.
AB  - OBJECTIVES: To assess health care use and costs for benign prostatic hyperplasia
      (BPH) in Sweden from 1987 to 1994 when minimal invasive procedures, including
      transurethral microwave therapy (TUMT) and drugs, were introduced, in addition to
      conventional surgery. METHODS: Cross-sectional annual data on health care
      utilization based on national information systems and surveys were used for
      calculation of direct 1994 cost. RESULTS: The total number of men in the age
      group at risk for BPH was virtually constant, and the total direct health care
      costs for BPH treatment increased from 1987 to 1992. A slight decrease was
      evident for the years 1993 and 1994, notwithstanding the introduction of new
      ambulatory procedures in 1991 and of new drugs in 1992. The number of physician
      office visits changed little during the study period, although this estimate may
      be low. TUMT procedures were introduced rapidly but decreased; nevertheless,
      their share was never more than 3% of total costs. Drug sales were 15-fold those
      in 1992 and accounted for 12% of the total costs in 1994. Conventional
      transurethral resection of the prostate (TURP) operations decreased markedly
      after the introduction of the new treatments. CONCLUSIONS: The new treatments
      were adopted differently. TUMT procedures decreased as rapidly as they were
      introduced. Three years after the introduction of the new drugs, drug sales
      indicated that the number of men receiving drug treatment was greater than the
      annual number of men receiving TURP operations and TUMT procedures combined. Yet
      the total costs showed a slight decrease, mainly due to the decreasing numbers of
      TURP operations.

PMID- 9255292
TI  - Quantitative assessment of uroflow: is there a circadian rhythm?
AB  - OBJECTIVES: To investigate if the circadian rhythm of urinary flow values varies
      within groups of patients with varying degrees of bladder outlet obstruction.
      METHODS: A total of 170 patients with lower urinary tract symptoms suggestive of
      bladder outlet obstruction used a home-based uroflowmeter and produced a total of
      1670 correctly measured flows at home. These patients also underwent a screening
      program with free urinary flowmetry in the hospital and a urodynamic pressure and
      flow study. RESULTS: There is a circadian variability in urinary flow values in
      men with higher grades of obstruction. These men have a higher peak urinary flow
      with a smaller voided volume and thus a shorter flow time in the early afternoon
      when compared with late evening, early morning, and the midnight to morning
      periods. CONCLUSIONS: This significantly greater maximum flow in the afternoon in
      men with higher grades of obstruction can be an important bias in studies where
      the primary end point is to assess a small improvement in maximum flow.
      Therefore, the circadian rhythm of uroflow has to be taken into account in the
      evaluation of the efficacy of treatment. Patients participating in clinical
      research studies should produce their urinary flow in the clinic always during
      the same time period, either in the morning or in the afternoon, and should not
      switch their appointment time.

PMID- 9255295
TI  - Effect of ejaculation on serum total and free prostate-specific antigen
      concentrations.
AB  - OBJECTIVES: Measurement of total serum prostate-specific antigen (PSA) is widely
      used as an aid to early detection of prostate cancer. Measurement of the ratio of
      free to total PSA may increase the specificity of PSA testing. To improve
      specificity further, other factors that may cause transient increases in PSA,
      such as ejaculation, have been identified. We prospectively studied the effect of
      ejaculation on total and free PSA levels and examined whether changes induced by
      ejaculation would affect recommendations for performing prostatic biopsy.
      METHODS: We measured the baseline total and free serum PSA levels and obtained
      measurements 1.6, and 24 hours after ejaculation in 20 volunteers (mean age 59
      years). All men had baseline PSA levels less than 4.0 ng/mL. We used repeated
      measures analysis of variance to test for changes in total, free, and percent
      free PSA after ejaculation. We also calculated the proportion of men with PSA
      levels greater than the expected biologic variability at each timepoint. RESULTS:
      The mean total, free, and percent free serum PSA increased 1 hour after
      ejaculation. Mean total PSA levels remained significantly increased 6 and 24
      hours after ejaculation. Mean free PSA decreased to baseline levels by 6 hours
      after ejaculation, and percent free PSA returned to baseline by 6 hours after
      ejaculation and then decreased below baseline by 24 hours. When normal biologic
      variation was accounted for, 40% of men, at 24 hours after ejaculation, had total
      PSA levels above the baseline level. Similarly, 24 hours after ejaculation, the
      percent free PSA remained above baseline level in 10% and below baseline level in
      35% of the men. CONCLUSIONS: Both total and free PSA increase immediately after
      ejaculation, with differing rates of return to baseline levels. PSA testing
      within 24 hours after ejaculation may lead to an erroneous interpretation of the
      results of both total and percent free PSA measurements in a small proportion of
      men.

PMID- 9255294
TI  - Clinical outcome at 3 months after transurethral vaporization of prostate for
      benign prostatic hyperplasia.
AB  - OBJECTIVES: To evaluate the clinical outcome of transurethral vaporization of the
      prostate (TUVP) for the management of benign prostatic hyperplasia (BPH).
      METHODS: Between March and June 1995, 30 patients with symptomatic BPH treated by
      TUVP were enrolled in this study. Transrectal ultrasonography (TRUS) was done
      preoperatively. American Urological Association (AUA) symptom score
      determination, pressure flow study, and questionnaire (for evaluating potency)
      were done preoperatively and 3 months postoperatively. RESULTS: The average age
      was 70.5 years (range 60 to 83) and estimated prostate size by TRUS before
      surgery was 33.8 +/- 14.0 g. The average AUA symptom score decreased
      significantly 3 months after TUVP (6.2 +/- 7.8 versus 18.2 +/- 9.0; P < 0.01).
      The maximum urine flow rate (Qmax) was 11.1 +/- 3.7 mL/min before TUVP (mean +/-
      SD) and 17.0 +/- 6.5 mL/min 3 months after TUVP, whereas the detrusor pressure at
      maximum urine flow (Pdes at Qmax) was 61.0 +/- 23.9 and 41.2 +/- 15.2 cm H2O,
      respectively. Qmax increased and Pdes at Qmax decreased significantly 3 months
      after TUVP. Of the 30 patients, 3 (10%) developed bladder neck contracture. Of
      the 24 patients who were potent sexually before operation, 3 (12.5%) developed
      impotence 3 months after surgery. CONCLUSIONS: TUVP is an effective alternative
      surgical procedure to relieve obstruction for patients with symptomatic BPH.
      However, cautious attitude on its usage is advocated based on our preliminary
      results indicating the occurrence of late complication such as impotence and
      bladder neck contracture.

PMID- 9255293
TI  - Doxazosin in men with lower urinary tract symptoms: urodynamic evaluation at 15
      months.
AB  - OBJECTIVES: To assess the results of doxazosin treatment in men with lower
      urinary tract symptoms (LUTS) treated for 15 months and to correlate symptomatic
      changes with alterations in urodynamic measures. METHODS: After an initial 3
      month treatment period with doxazosin 4 mg/day, 50 men with LUTS were given the
      choice of continued treatment with this agent or other therapeutic options. All
      patients were evaluated by International Prostate Symptom Score (IPSS)
      questionnaires and urodynamic evaluation initially and after 3 months of
      treatment. Patients were followed for an additional 12 months and those who
      continued doxazosin treatment underwent repeat urodynamic testing. RESULTS: Among
      the original 50 patients, 24 men (48%) continued doxazosin treatment for 15
      months, 18 men (36%) discontinued therapy, and 8 men (16%) were either dead or
      lost to follow-up or had been diagnosed and treated for prostate cancer.
      Comparison of values at 3 and 15 months of follow-up (9.4 versus 13.4, P = 0.03)
      showed significant worsening of voiding symptoms, as assessed by the IPSS, in the
      24 men still receiving doxazosin. This deterioration of subjective results with
      doxazosin occurred despite continued improvements in peak urinary flow rate
      (Qmax), detrusor pressure at peak flow (PdetQmax), and objective measures of
      obstruction (Abrams-Griffiths number) from 3 to 15 months of follow-up.
      CONCLUSIONS: Relief of voiding symptoms in men with LUTS treated with doxazosin
      over prolonged intervals of 15 months does not correlate well with changes in
      urodynamic measures.

PMID- 9255296
TI  - Positive prostate-specific antigen circulating cells detected by reverse
      transcriptase-polymerase chain reaction does not imply the presence of prostatic
      micrometastases.
AB  - OBJECTIVES: Detection of circulating tumor cells may improve the preoperative
      local staging of prostate cancers. The aim of this study was to perform enhanced
      reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate-specific
      antigen (PSA) mRNA to define the predictive value of PSA-positive circulating
      cells in a large series of patients. METHODS: The study included 46 patients with
      Stage T1 to T2 prostate cancer, 94 with benign prostatic hyperplasia (BPH), and
      51 (including 9 women) with nonprostatic disease. PSA-positive cells from
      peripheral blood samples were detected by Southern blot analysis of the RT-PCR
      products. Original oligonucleotide primers were defined to exclusively detect the
      three PSA mRNA splices. RESULTS: Circulating PSA-positive cells were observed in
      8 (8.5%) of 94 patients with BPH, 10 (22%) of 46 with Stage T1 to T2 prostate
      cancer, and 9 (17.6%) of 51 with nonprostatic disease. The detection rate of PSA
      positive circulating cells was significantly increased in patients with prostate
      cancer versus patients with BPH (P = 0.03). Among clinically localized prostate
      cancers with a Gleason score less than 8, a correlation was observed between PSA
      positive circulating cells and Stage pT3 cancer (P = 0.038), capsular penetration
      (P = 0.04), and a positive margin (P = 0.038). The specificity of the assay for
      Stage pT3 cancer detection was 84.6%, with a positive predictive value of 60%.
      CONCLUSIONS: Although RT-PCR assay may have a role in preoperative local staging,
      this study demonstrated the absence of tissue and tumor specificity of PSA
      positive circulating cells, accounting for the weak positive predictive value of
      this technique.

PMID- 9255297
TI  - Stage D1 (T1-3, N1-3, M0) prostate cancer: a case-controlled comparison of
      conservative treatment versus radical prostatectomy.
AB  - OBJECTIVES: There is no consensus on the management of Stage D1 prostate cancer.
      The literature suggests that radical prostatectomy, as compared with pelvic
      lymphadenectomy (PLND) alone, may extend survival, Despite evidence that lymph
      node tumor burden influences cancer survival, few groups of researchers have
      controlled for this variable when comparing management strategies. We performed a
      study that was case-controlled for nodal tumor burden to determine if a survival
      advantage exists for radical prostatectomy. METHODS: Of 168 men with Stage D1
      disease diagnosed between 1983 and 1995, 127 underwent pelvic lymphadenectomy and
      radical retropubic prostatectomy (PLND/RRP) and 41 underwent PLND alone. Clinical
      charts were reviewed for follow-up, and lymph node tumor burden was assessed by
      volume of nodal metastases and the percentage of positive nodes sampled. Adjuvant
      treatment was based on the surgeon's preference and clinical situation. Nineteen
      patients from each group were matched for age, PSA, Gleason score, clinical
      stage, follow-up, and nodal tumor burden. RESULTS: Comparison of the non-case
      controlled PLND/RRP and PLND groups showed no differences in age, prostate
      specific antigen level, Gleason score, clinical stage, or follow-up. The nodal
      tumor burden was greater for the PLND group (P = 0.001). The 10-year cancer
      specific survival rates for the PLND/RRP and PLND groups were statistically
      different (P = 0.006). In the case-controlled group, the results were similar for
      cancer-specific survival at 10 years (56% and 34%, respectively; P = 0.09).
      CONCLUSIONS: These data suggest that in Stage D1 prostate cancer, a trend toward
      a statistical difference in survival may exist for radical prostatectomy as
      compared with conservative treatment. Further case-controlled and prospective
      randomized studies are needed to verify these results.

PMID- 9255298
TI  - Reduction in testicular temperature after varicocelectomy in infertile men.
AB  - OBJECTIVES: To study the effects of varicocelectomy on testicular temperature.
      METHODS: Testicular skin surface temperature was directly measured with an
      electronic thermometer calibrated to 0.01 degree C in 119 men before and after
      microsurgical varicocelectomy and in 45 control patients without varicocele.
      RESULTS: Testicular temperatures in men with varicocele were elevated
      preoperatively (right side [R]: 34.00 +/- 0.91 degrees C/left side [L]: 34.37 +/-
      0.87 degrees C unilateral; R: 34.07 +/- 0.83 degrees C/L: 34.34 +/- 0.85 degrees
      C bilateral) relative to control patients (R: 33.04 +/- 2.47 degrees C/L: 32.86
      +/- 2.52 degrees C) (P < 0.01). Postoperative temperatures were unchanged in the
      control patients. Testicular temperatures decreased after both bilateral and
      unilateral varicocelectomy (R: 33.03 +/- 0.85 degrees C/L: 32.84 +/- 1.0 degrees
      C unilateral; R: 33.27 +/- 1.0 degrees C/L: 33.54 +/- 1.2 degrees C bilateral) to
      levels nearly identical to those of control patients (P < 0.001). CONCLUSIONS:
      Testicular temperatures were elevated bilaterally in men with both unilateral and
      bilateral varicoceles. Both unilateral and bilateral microsurgical
      varicocelectomy results in a bilateral decrease in testicular temperature. These
      results support the hypothesis that a defect in testicular thermoregulation
      contributes to the pathophysiology of varicocele and demonstrate, for the first
      time in humans, the efficacy of varicocelectomy in restoring normal testicular
      temperatures.

PMID- 9255299
TI  - Renal transplantation in children following augmentation ureterocystoplasty.
AB  - OBJECTIVES: To assess the impact of augmentation ureterocystoplasty on the
      success of cadaveric renal transplantation in children with dysfunctional
      bladders. METHODS: Two patients with end-stage renal failure secondary to
      dysfunctional bladders (one myelodysplasia and one posterior urethral valves)
      underwent augmentation ureterocystoplasty prior to renal transplantation in order
      to increase bladder capacity and improve compliance. RESULTS: Significant
      improvement of bladder storage function was achieved in both patients. By the use
      of megaureter for augmentation, untoward sequelae of enteric or gastric
      augmentation were obviated. Renal transplantation was successful in both
      patients. Both have normal renal function 4 and 3 years after transplantation.
      CONCLUSIONS: Renal transplantation into bladders previously augmented with
      megaureters is successful. The use of urothelial-lined biomaterial for
      augmentation avoids the potential complications of gastro- or enterocystoplasty,
      which are especially dangerous in transplant patients.

PMID- 9255300
TI  - Skin flap closure by dermal laser soldering: a wound healing model for sutureless
      hypospadias repair.
AB  - OBJECTIVES: Laser tissue soldering (LTS) with the diode laser and human albumin
      hyaluronate-indocyanine green solder is a safe and effective method of providing
      an immediate leak-free closure during hypospadias repair. In this report, we
      compare the physiology, histology, and immunohistochemistry of wound healing
      following LTS and suturing in a rat skin flap model. METHODS: A 4 x 5-cm skin
      flap was raised and bisected (4 cm) on the dorsum of 48 Sprague-Dawley rats. The
      central wound was either closed from a dermal approach by suturing or LTS or left
      open, and studied at 0, 3, 5, 7, 10, 14, and 21 days postoperatively. An
      intraoperative comparison was made between suturing and LTS with respect to
      operative time. Postoperatively, flaps were excised for tensiometric analysis,
      and sections were stained with hematoxylin-eosin to define wound architecture.
      Resting skin temperature, laser exposed temperature without solder, and maximum
      temperature with solder (one drop) were measured at the level of the deep dermis,
      superficial striated muscle layer, and within the solder. Mean peak temperatures
      were recorded during a 1-minute laser activation time. RESULTS: Mean continuous
      suturing time (4.9 +/- 1.1 minutes) was significantly (P < 0.001) faster than
      either LTS (7.7 +/- 0.77 minutes) or discontinuous suturing (8.2 +/- 0.62
      minutes). Two seromas (sutured) and two instances of partial wound dehiscence (1
      sutured, 1 LTS) were noted. Tensile strength was increased significantly (P <
      0.001) for up to 5 days in the LTS group, but was equal to suturing at 7 and 10
      days. Immediate tensile strength after LTS was equivalent to a 7-day healed
      wound. At 14 days, wounds initially left open and those closed by LTS were
      stronger than sutured wounds (P < 0.05). There was no evidence of thermal injury
      or foreign body reaction in the LTS group. Solder was incorporated within the
      dermis in all wounds at 21 days. Laser activation of solder resulted in
      significant increases in temperature at all three tissue levels: 65.0 +/- 5.2 and
      69.9 +/- 6.8 degrees C in the deep and superficial skin (no significant
      difference between the two), and 101 +/- 15.6 degrees C within the solder (P <
      0.001 versus superficial and deep skin). CONCLUSIONS: Our results indicate that
      sutureless dermal LTS of skin flaps provides increased tensile strength for up to
      7 days, with relatively greater tensile strength provided within the first 3
      days. Our laser technique does not appear to alter the normal wound healing
      process. Rather, solder-tissue interaction initially, and extracellular matrix
      infiltration of solder later, provide the basis for improved wound strength. For
      hypospadias repair using skin flaps, these wound attributes may permit sutureless
      surgery.

PMID- 9255301
TI  - A method for intraoperative adjustment of sling tension: prevention of outlet
      obstruction during vaginal wall sling.
AB  - OBJECTIVES: To describe a simple, yet effective method of adjusting
      intraoperative tension on the suspending sutures of a vaginal wall sling placed
      for treatment of stress urinary incontinence (SUI) in the female patient.
      METHODS: A cystoscope sheath is placed per urethra and inclined to approximately
      20 degrees to 30 degrees relative to horizontal. The suspension sutures are tied
      down directly onto the rectus fascia but do not indent it. The sheath should
      easily rotate in the vertical plane within the urethral lumen, maintaining
      elastic mobility as the sutures are tied. RESULTS: On review of the first 160
      patients who have undergone vaginal wall sling using this technique of tension
      adjustment, no patient has had unexpected permanent urinary retention.
      Preoperative urgency incontinence has remained in 10 patients (less than 7%)
      postoperatively; 11 patients (6.8%) have had recurrent SUI during follow-up.
      CONCLUSIONS: Proper adjustment of suture tension during performance of a sling
      procedure for SUI is critical in preventing urethral obstruction. The technique
      described is simple, objective, reproducible, and highly effective.

PMID- 9255302
TI  - The Turner biopsy needle facilitates seminal vesicle aspiration.
AB  - Transrectal ultrasonography and seminal vesicle aspiration with or without
      vesiculography have become an integral part of the evaluation and management of
      the infertile male with ejaculatory duct obstruction. We have found that the Echo
      Tip Turner Biopsy Needle used in conjunction with ultrasound guidance greatly
      facilitates these transrectal procedures.

PMID- 9255303
TI  - Renal tubular acidosis.

PMID- 9255304
TI  - Fibroepithelial polyp of the ureter.

PMID- 9255305
TI  - Renal artery thrombosis in the newborn infant.
AB  - Renal artery thrombosis is rarely encountered in the pediatric population. The
      recent literature associates its occurrence with the use of umbilical artery
      catheterization. This report describes renal artery occlusion in 2 patients with
      severe cardiac disease who developed renal artery thrombosis a few weeks after
      birth. One patient had undergone umbilical artery catheterization months before
      he developed the renal artery occlusion. The second patient never had umbilical
      artery catheterization. Neither patient recovered renal function in the affected
      kidney despite systemic anticoagulation.

PMID- 9255306
TI  - Inflammatory (pseudosarcomatous) myofibroblastic tumor of the bladder.
AB  - We present a case of inflammatory (pseudosarcomatous) myofibroblastic tumor of
      the bladder in a child, along with a review of the literature. The benign nature
      of this rare disorder needs to be recognized so that superfluous radical therapy
      can be avoided. The clinical features and microscopic, ultrastructural, and
      immunohistochemical characteristics that help to identify this entity are
      described. To date, 72 such cases involving the bladder have been reported in the
      literature including the present one.

PMID- 9255307
TI  - Metabolic complications secondary to obstruction of a Kock pouch afferent limb.
AB  - Metabolic complications are frequently seen following urinary diversion with an
      intestinal segment. Afferent limb complications are noted in 10% of patients
      undergoing continent Kock urinary diversion. We present a patient with cloacal
      exstrophy with developed significant hypocalcemic tetany and metabolic acidosis
      related to a nondraining afferent limb of a Kock pouch created to achieve
      continence.

PMID- 9255308
TI  - Development of a malignant peripheral nerve sheath tumor following treatment for
      testicular seminoma.
AB  - A novel case is reported in which an S2 nerve root malignant peripheral nerve
      sheath tumor was diagnosed approximately 8 years after treatment for Stage I
      testicular seminoma. This patient underwent right orchiectomy and subsequent
      irradiation therapy to the periaortic region, including the sacrum. Postoperative
      radiation therapy likely played a role in the development of this second
      malignancy.

PMID- 9255309
TI  - Progelatinase A mRNA expression in cell lines derived from tumors in patients
      with metastatic renal cell carcinoma correlates inversely with survival.
AB  - OBJECTIVES: Tumors are thought to metastasize by a process involving tumor cell
      attachment to extracellular matrix, degradation of matrix components by tumor
      associated proteases, and cellular movement into the area modified by protease
      activity. Type IV collagen comprises the major element tumor cells must degrade
      to gain access to the rest of the body. Renal cancer cell line progelatinase A
      (E.C. 3.4.24.24; 72-kDa type IV collagenase; MMP-2) mRNA expression was
      correlated with patient survival. METHODS: Total cellular mRNA was extracted from
      tumor cell lines derived from patients with metastatic renal cell carcinoma. The
      results of the densitometric analysis of Northern blots were correlated with
      patient survival. Formalin-fixed, paraffin-embedded tissue sections of primary
      renal cancers were examined for immunohistochemical expression of MMP-2. RESULTS:
      Cell lines established from 23 primary renal tumors and six metastatic sites in
      26 patients with metastatic renal carcinoma were studied. Variable expression of
      progelatinase A, relative to A2058 melanoma cells (mean +/- SEM, 0.60 +/- 0.21;
      median, 0.082; range, 0 to 4.78), was found. There was a significant inverse
      association between patient survival and the log of the MMP-2 expression (P =
      0.045 by the Cox proportional-hazards model). Using a cutoff value of 0.10, the
      closest round number to the median expression of MMP-2, a significant difference
      between survival of patients with lower and higher MMP-2 expression in their
      primary renal cell line was found (P = 0.0054). Cell lines with low,
      intermediate, and high expression of MMP-2 mRNA all had primary tumors with high
      tissue immunohistochemical expression of MMP-2. CONCLUSIONS: These studies
      demonstrate an inverse relationship between renal cancer cell line MMP-2 mRNA
      expression and patient survival. Immunohistochemical studies of the primary
      tumors from which the cell lines were derived uniformly showed high MMP-2
      expression. Previous work suggests local renal factors upregulate cellular
      expression of MMP-2 in the primary tumor, and are not active at extrarenal sites.

PMID- 9255311
TI  - Ileal reservoir for bladder replacement.

PMID- 9255310
TI  - Identification of a novel transcript up-regulated in a clinically aggressive
      prostate carcinoma.
AB  - OBJECTIVES: To identify differentially expressed genes in tumor cells of patients
      with prostate cancer by means of tissue microdissection and targeted differential
      display. METHODS: RNA was recovered from pure populations of microdissected
      normal epithelium and invasive tumor from frozen tissue sections of a radical
      prostatectomy specimen. Reverse transcription-polymerase chain reaction (PCR)
      using arbitrary and zinc finger PCR primers was performed. RESULTS: A 130-base
      pair product was identified that appeared selectively in the tumor sample. DNA
      sequence analysis revealed it to be a clone from the expressed sequence tag
      database (GenBank accession R00504). Microdissection of normal epithelium and the
      corresponding invasive tumor was subsequently performed on a test panel of 10
      prostate carcinoma specimens. Comparison of R00504 levels in normal epithelium
      and invasive carcinoma, using beta-actin as an internal control, showed the
      transcript to be substantially overexpressed in 5 of 10 carcinomas. Northern
      blotting revealed R00504 to be a 2.6-kilobase gene. CONCLUSIONS: A novel
      transcript up-regulated in an aggressive prostate carcinoma was identified using
      degenerate zinc finger primers in microdissected tissue samples. The approach
      used in this study may be helpful in quantitative comparison of known genes and
      identification of novel genes in microdissected human tissue samples.

PMID- 9255312
TI  - Estimated potency of Casodex: a problematic design.

PMID- 9255315
TI  - Radical prostatectomies.

PMID- 9255313
TI  - Laparoscopic orchidopexy.

PMID- 9255314
TI  - Circumcision in infancy.

PMID- 9255316
TI  - Retrograde urogram for ureteral pseudodiverticulosis.

PMID- 9255318
TI  - 13th Annual meeting of the Society for the Study of Reproduction. Portland,
      Oregon, August 2-5, 1997. Abstracts.

PMID- 9255319
TI  - 7th International Symposium on Cardiovascular Pharmacotherapy. Jerusalem, Israel,
      June 1-5, 1997. Abstracts.

PMID- 9255320
TI  - 2nd Joint meeting of the Society for Clinical Trials and the International
      Society of Clinical Biostatistics. Boston, Massachusetts, July 6-10, 1997.
      Abstracts.

PMID- 9255317
TI  - Interferon alfa-2b for treatment of subclinical intraurethral human papilloma
      virus infection.

PMID- 9255322
TI  - 8th European Congress on Obesity. Dublin, 18-21 June, 1997. Abstracts.

PMID- 9255321
TI  - VIth International Congress of Andrology, Salzburg, Austria, 25-29 May 1997.
      Abstracts.

PMID- 9255324
TI  - Author and subject index volume 36, 1996.

PMID- 9255323
TI  - 8th International Conference on Bioinorganic Chemistry. Yokohama, Japan, July 27
      August 1, 1997. Abstracts.

PMID- 9255325
TI  - Plasma exchange is not excluded as a useful therapy in vasculitis-associated
      glomerulonephritis.

PMID- 9255326
TI  - Treatment of glomerulonephritis in microscopic polyangiitis and Churg-Strauss
      syndrome. Indications of plasma exchanges, Meta-analysis of 2 randomized studies
      on 140 patients, 32 with glomerulonephritis.
AB  - Although plasma exchanges (PE) have no added benefit in the treatment of
      vasculitides of the polyarteritis nodosa (PAN) group with steroids (CS) +/-
      cyclophosphamide (CY), this has not been demonstrated in patients presenting with
      glomerulonephritis (GN). We therefore reanalyzed the records of microscopic
      polyangiitis (MPA) or Churg-Strauss syndrome (CSS) patients presenting with GN.
      PATIENTS AND METHODS: Patients were included consecutively in 2 randomized
      trials: a) comparing CS vs CS + PE (n = 78) and b) comparing CS + pulse CY +/- PE
      in PAN and CSS with factors of poor prognosis (n = 62); 9-12 PE/patient were
      performed. RESULTS: 32 patients, 18 men and 14 women, presented with GN, 28 MPA
      and 4 CSS, mean age 53.2 +/- 17 years. Clinical/biological manifestations before
      treatment were comparable in both groups: weight loss 84.4%, fever 62.5%,
      mononeuritis multiplex 62.5%, purpura 28.1%, GI tract involvement 43.8%,
      arthritis 37.5%, asthma 12.5%, CNS manifestations 9.4%; cardiac involvement 9.4%;
      mean creatininemia was 303 +/- 286 mumol/l, proteinuria > 0.5 g/l or 1g/d was
      found in every case, microscopic hematuria in 20/32 patients, leukocyturia in
      12/32. Eight out of/16 were ANCA-positive, ELISA detected anti-MPO antibodies in
      5 and anti-PR3 in 3. HBV infection was never observed. After 1 year of treatment,
      creatininemia decreased from 374.4 +/- 352 to 290 +/- 352 mumol/l in the PE group
      and from 287 +/- 292 to 170 +/- 67 in the non PE group (NS). Six patients of the
      PE group and 2 of the non-PE group were dialyzed at onset of treatment. Four of
      the 6 PE patients and 1 of the 2 not treated with PE were off dialysis 1 year
      later. In addition 1 patient from the PE group developed a flare with renal
      failure and required chronic dialysis. The 5-year survival was higher in the PE
      group (4 deaths/19) than in the non PE group (7/13). The survival curve was 74%
      in the PE group vs 54% in the non-PE group (NS). CONCLUSION: This study confirms
      that PE have no added benefit in the treatment of GN in MPA and CSS.

PMID- 9255327
TI  - Anti-Ro (SSA) and anti-La (SSB) antibodies and complete congenital heart block.
AB  - Complete congenital heart block (CCHB) is the most severe manifestation of
      neonatal lupus syndrome, associated with a mortality rate of up to 31%. It is
      caused by irreversible damage to the cardiac conduction system due to the
      transplacental passage of maternal antibodies to the fetus. Anti-Ro (SSA) and
      anti-La (SSB) antibodies are usually detected in sera of mothers of children with
      prenatally diagnosed CCHB and in cardiac tissues of affected newborns. Their
      pathogeneic role in the development of CCHB has been established in several
      studies. When CCHB is detected during pregnancy, careful monitoring and delivery
      are needed before heart failure is developed. Treatment strategies are debatable
      and may include prophylactic therapy for high-risk pregnant women and a
      combination of intrauterine plasmapheresis with plasma exchange or with
      corticosteroids. Pacemaker insertion is required in most infants during the first
      three months of life. Assays for anti-Ro (SSA) and anti-La (SSB) antibodies
      should be performed on sera of pregnant women with SLE and newborns with CCHB.

PMID- 9255328
TI  - [Buccal dryness, xerostomia and measurement of salivary secretory activity].
AB  - Xerostomia is a marked reduction in saliva production and may occur as an early
      symptom of various systemic diseases. It is also secondary to the administration
      of numerous drugs. Severity of salivary gland dysfunction cannot be predicted
      from subjective reports of oral dryness by patient, and accurate assessments of
      salivary gland function should be managed. Several procedures for saliva
      samplings and secretory activity measurements have been reported. In normal
      individuals, the mean values of unstimulated whole saliva was slightly higher in
      males (0.42 ml/min) than in females (0.37 ml/min). Corresponding mean values for
      stimulated whole saliva are 1.77 ml/min and 1.38 ml/min. Unstimulated whole
      saliva collection during 15 min is recommended as the most reliable test for
      clinical diagnosis. It is found that an unstimulated salivary flow of 0.1 ml/min
      represents the cut-off limit for the diagnosis of xerostomia.

PMID- 9255329
TI  - [Prevention of bacterial infections in immunocompromised hosts, excluding HIV
      infection and mycobacterium infections].
AB  - The immunocompromised host is an individual whose defense mechanisms against
      infectious agents are altered in such a significant way that he is abnormally
      susceptible to infections agents in general and bacterial "opportunists" in
      particular. The type of infection and etiologic agents vary with the nature and
      the severity of the immune defect. The goal of prophylactic treatments is to
      prevent the occurrence or recurrence of infections, and so, to reduce the
      infectious morbidity and mortality when the nature of severity of
      immunosuppression make these complications probable. Beside specific measures,
      which are detailed in this article, the strict application of the so-called
      universal precautions, particularly handwashing, remain at the basis of the
      prevention of bacterial infections in the immunocompromised host.

PMID- 9255330
TI  - [Prevention of tuberculosis in immunocompromised patients].
AB  - Immunosuppressed patients have an increased risk of developing active
      tuberculosis, either by reactivation of an old infection, or by horizontal
      acquisition during a contact with a contagious tuberculous patient. The diagnosis
      of tuberculosis requires a clinical examination and the realization of a PPD skin
      test and a pulmonary radiograph. Symptomatic tuberculosis is a contra-indication
      to chemoprophylaxis and requires a full curative treatment. The decision to
      undertake chemoprophylaxis should be individual. When indicated, it relies
      classically on a 6-month regimen of isoniazid. Short term chemoprophylactic
      regimens, such as rifampicin-isoniazid during 3 months or rifampicin-pyrazinamide
      during 2 months, have shown some efficacy. The interaction of rifampicin with
      corticosteroids or ciclosporin often impedes the use of this antibiotic. Apart
      from HIV infection, no clinical study of chemoprophylaxis is available in
      immunosuppressed patients.

PMID- 9255331
TI  - [Prevention of atypical mycobacterium infections in immunocompromised patients].
AB  - Unusual before AIDS epidemic, non tuberculosis mycobacterial infections were
      observed in HIV-infected patients with CD4 cells count less than 75/mm3. Primary
      prophylaxis with rifabutin, clarithromycin or azythromycin may be used. Secondary
      prophylaxis are necessary with association of two or three drugs among
      clarithromycin, azythromycin, ethambutol and rifabutin. In immunocompromised
      patients, without HIV infection, risk of disseminated infection seems lower, but
      no study evaluate it.

PMID- 9255332
TI  - [Prevention of toxoplasmosis in immunocompromised patients].
AB  - The main underlying immunosuppressive conditions requiring prevention of
      toxoplasmosis are organ transplantations (especially heart and bone marrow
      transplants) and advanced HIV infection (CD4 + lymphocytes count < 100/mm3).
      Preventive strategies consist in reducing the rate of primary infection, mainly
      through hygiene and diet measures, and introducing chemoprophylaxis in patients
      already contaminated by the parasite: the most precise knowledge in this field
      concerns HIV infected patients. For prevention of recurrence, patients should
      receive pyrimethamine-sulfadiazine, or otherwise pyrimethamine-clindamycin
      combinations. For primary prophylaxis, cotrimoxazole is the first-line therapy.
      If patients cannot tolerate cotrimoxazole, a regiment including dapsone plus
      pyrimethamine is a possible alternative; pyrimethamine alone and atovaquone are
      currently under investigation.

PMID- 9255333
TI  - [Prevention of parasitic infections (excluding toxoplasmosis) in
      immunocompromised patients].
AB  - Immunocompromised patients, notably those with cell mediated immunity deficiency,
      are at risk for severe and life-threatening parasitic infections. Severity and
      frequency of Pneumocystis carinii pneumonia have led to systematically initiate
      prophylaxis for high-risk patients such as patients with HIV infection, hemopathy
      or renal transplants. Cotrimoxazole has shown the best efficacy both in primary
      and secondary prophylaxis. Side effects, notably skin rash, constitute the major
      limiting factor of cotrimoxazole therapy. However, its efficacy in preventing
      cerebral toxoplasmosis and to a lesser extent bacterial infections, makes
      cotrimoxazole the drug of choice for HIV-positive patients in this direction.
      Aerosolized pentamidine is probably the best alternative considering its similar
      results in primary prophylaxis for patients with a CD4 count > or = 100/mm3.
      Dapsone, associated with pyrimethamine for toxoplasmosis prevention, and
      atovaquone represent other possible alternatives. Such a prevention is absolutely
      necessary for HIV patients with a previous history of pneumocystosis or with less
      than 200 CD4/mm3. Moreover, children with SCID or acute leukemia as well as
      patients with renal or heart-lung transplantation would benefit from
      pneumocystosis prophylaxis. The frequency of relapses of visceral leishmaniasis
      also justifies a secondary prophylaxis. Because of its efficacy on P. carinii,
      intravenous pentamidine could be considered the drug of choice. However
      preliminary studies have indicated the value of liposomal amphotericin B (1 mg/kg
      twice a month) in this setting. Finally, cryptosporidiosis and microsporidiosis
      would benefit from secondary prophylaxis. However, since first line therapy is
      not well established, further studies are needed to precisely determine which
      drug could be of value.

PMID- 9255334
TI  - [Primary and secondary prevention of cytomegalovirus infections in
      immunocompromised patients].
AB  - Seroprevalence for CMV varies from 70% in the general population to more than 90%
      in HIV infected patients. Immunodepression whatever its origin, either post
      therapeutic as in transplant recipients, or induced by HIV, leads to the
      reactivation of this virus, present in a latent form in the host. In CMV
      seronegative patients, the main prevention is based on donor matching before a
      graft (graft of seronegative donor) and on the use of seronegative blood products
      or deleukocyted blood. Since the availability of efficient strategies of
      prophylaxis (before infection) or of early treatment (pre-emptive therapy), CMV
      disease is now infrequent in most transplantation centers. A real prophylaxis
      with ganciclovir is usually selected in high risk patients (lung, bone marrow
      transplants in case of a CMV seropositive recipient or seronegative but with a
      seropositive donor). It has replaced in most centers aciclovir that has only a
      modest efficacy. A pre-emptive therapy by ganciclovir is proposed in case of
      lower risk of CMV disease (kidney, liver or heart transplants) or if the local
      virology laboratory provides sensitive virological markers to detect the first
      signs of CMV reactivation. Besides viremia or pp65 antigenemia, currently used to
      initiate a pre-emptive therapy, the standardisation of other virological markers
      such as leukocytic or plasmatic PCR is in progress. The prophylaxis of CMV
      disease in less developed for HIV infected patients. Immunosuppression,
      continuously progressing in absence of antiretroviral agents, requires a
      continuous prophylaxis for months or years, treatment that is difficult to
      propose at the present time considering the modest activity of oral ganciclovir,
      the only oral agent available. Future progresses in this field will be obtained
      when a sensitive and reproductible CMV marker will allow to identify the patients
      at highest risk of CMV disease, and with new anti-CMV agents having a good oral
      bioavailability.

PMID- 9255335
TI  - [Prevention of herpes simplex and varicella zoster infections in patients of HIV
      infections].
AB  - Reactivation of Herpes simplex virus and varicella zoster virus infections occurs
      frequently in patients infected with human immunodeficiency virus (HIV).
      Prevention of Herpes simplex recurrences with oral acyclovir (400 mg x 2/day)
      should be recommended for patients with more than 6 relapses per year. Varicella
      zoster immunoglobulin is recommended for prophylaxis of varicella in exposed HIV
      infected adults and children who are susceptible. Prevention of varicella-zoster
      recurrences with oral acyclovir (800 mg x 5/day) should be considered for
      patients with retinopathy.

PMID- 9255336
TI  - [Azole antifungal agents in the prevention of fungal infections in neutropenic
      patients and bone marrow graft recipients].
AB  - Fungal infections are often encountered in neutropenic patients and bone marrow
      graft recipients. Several studies have demonstrated the efficacy of antifungal
      prophylaxis. Regimens including azole compounds are increasingly used due to
      facilitate administration. The efficacy of fluconazole to prevent systemic
      candidiasis was recently documented in multicentric studies in bone marrow
      recipients but is more controversial in neutropenic patients. The risk of
      selecting strains of Candida with lower sensitivity to azole compounds must also
      be taken into consideration. There has not been any large study evidencing a
      primary prophylactic affect of itraconazole against invasive aspergillosis, but
      the results of multicentric studies should be available soon. Recent trials have
      attempted to determine how these compounds can best be used in empirical
      treatment of persistent fever in neutropenic patients and in secondary
      prophylaxis for mycoses during later intensive treatment protocols.

PMID- 9255337
TI  - [Prevention of infections in immunosuppressed patients: prevention of post
      transfusion infections].
AB  - CMV infection is the most severe transfusion-transmitted infection in
      immunosuppressed patients, and must be prevented in high-risk subjects by the use
      of seronegative units or by the use if leucocyte-reduced units. The value of
      these methods has been shown in patients who are seronegative for CMV.
      Allotransfusions may favor bacterial infections through negative immunomodulatory
      effects due to leucocytes. Finally, parvovirus can induce a more severe disease
      in immunosuppressed patients.

PMID- 9255338
TI  - [Vaccinations in immunosuppressed patients].
AB  - In immune deficiency of any cause, immunization is of great interest to avoid
      preventable infectious diseases but the risk of adverse events and suboptimal
      immunologic responses has to be considered. For live, attenuated vaccines, the
      main risks are post-immunization complications, especially in severely
      immunocompromised people. For killed or inactivated vaccines, there are no contra
      indications, but the immune response is reduced, leading to consider higher
      vaccine doses or more frequent boosters. However, the response to such
      modifications of vaccine schedules has not been systematically evaluated and
      definitive recommendations cannot be made at this time. In addition, in HIV
      infection, the effect of vaccination on viral replication has to be evaluated. In
      developing countries some live vaccines are still recommended in HIV+ children
      because of the prevalence of the target-diseases (measles, poliomyelitis,
      tuberculosis...) and the rarity of vaccine complications.

PMID- 9255339
TI  - Primary hepatic lymphoma associated with chronic hepatitis C.
AB  - Like other viruses (i.e Epstein'Barr virus), the role of hepatitis C virus is
      suspected in the pathogenesis of lymphoproliferative disorders. We report one
      case of primary hepatic malignant lymphoma associated with chronic hepatitis C
      viral infection. The diagnosis was obtained by percutaneous liver biopsy showing
      a non-Hodgkin's diffuse large cell lymphoma and micronodular cirrhosis. Serology
      for hepatitis C virus positivity was known three years before lymphoma diagnosis.
      Staging of the lymphoma confirmed multinodular primary hepatic lymphoma with no
      other detectable localisation. Complete remission has been obtained with
      aggressive chemotherapy. The role of hepatitis C virus in the pathogenesis of the
      lymphoma is unknown. An indirect mechanism is suspected. Chronic inflammation may
      evolve from polyclonal lymphocytic proliferation to true non-Hodgkin's lymphoma,
      as it has been suggested for non-Hodgkin's lymphoma in the emergence of
      cryoglobulinemia in hepatitis C positive patients.

PMID- 9255340
TI  - [Polyuro-polydipsia syndrome and renal failure in a patient treated with
      lithium].

PMID- 9255341
TI  - [Inflammatory pseudotumor of the liver].

PMID- 9255342
TI  - [Kawasaki syndrome in adults: treatment with polyvalent intravenous
      immunoglobulins].

PMID- 9255343
TI  - [Autoimmune polyneuropathy associated with hepatitis C].

PMID- 9255344
TI  - [Toxiderma induced by fosfestrol (ST52)].

PMID- 9255345
TI  - [Acute pancreatitis and Zieve syndrome: an uncommon association].

PMID- 9255346
TI  - [Pharmacological control of biosynthesis pathway of mevalonate: effect on the
      proliferation of arterial smooth muscle cells].
AB  - The role of mevalonic acid (MVA) and its products (isoprenoids) in cell
      proliferation prompted us to investigate the effect of drugs affecting diverse
      enzymatic steps of the MVA pathway on rat aorta smooth muscle cell (SMC)
      proliferation. Competitive inhibitors of HMG-CoA reductase (statins) decreased
      SMC proliferation in a dose-dependent manner. The inhibitory effect induced by
      simvastatin 3.5 microM (70% +/- 3.8 decrease) was prevented by addition of 100
      microM MVA, (100% +/- 2.3), 10 microM farnesol (F-OH) (85% +/- 1.2) and 5 microM
      of all-trans geranylgeraniol (GG-OH) (precursor of prenylated proteins) (81% +/-
      1.1), but not by 2-cis GG-OH (precursor of dolichols), squalene and ubiquinone.
      The same inhibitory effect was obtained with 6-fluoromevalonate (1-50 microM), an
      inhibitor of MVA-PP decarboxylase. Squalestatin 1 (1-25 microM) and NB-598 (1-10
      microM), potent squalene synthase and epoxidase inhibitors, respectively, caused
      a complete inhibition of cholesterol synthesis without affecting SMC
      proliferation. Finally, BZA-5B (10-50 microM) a specific inhibitor of protein
      farnesyl tranferase (PFTase), inhibited SMC proliferation in a dose- (10-50
      microM) and time-dependent manner, reaching 52% +/- 6.3 inhibition after 9 days,
      in the presence of 50 microM BZA-5B, without affecting cholesterol synthesis.
      This effect was partially prevented by mevalonate (76% +/- 3.2) and GG-OH (87% +/
      7.3) but not by F-OH. On the other hand, SMC proliferation was not affected by
      the closely related compound BZA-7B (93% +/- 4), which does not inhibit PFTase.
      Taken together, these findings support the involvement of specific isoprenoid
      metabolites, probably through farnesylated and geranylgeranylated proteins in
      cell proliferation.

PMID- 9255347
TI  - [Isoprenylated proteins and cell proliferation: regulators and effectors of Ras
      proteins].
AB  - Ras proteins play a central role in the control of cellular proliferation. They
      are 189 amino acid monomeric GTP-binding proteins that cycle between an inactive
      GDP-bound and the active GTP-bound state, and carry a slow intrinsic GTPase
      activity. Ras proteins are activated by growth promoting signals incoming from
      receptor tyrosine kinases via SH2 domain and SH3 domain containing adapter
      proteins and the Ras exchange factor Sos, as well as from serpentine receptors
      via the beta gamma subunits of heterotrimeric G proteins and the Ras exchange
      factor Ras-GRF (or Cdc25). Proteins that can stimulate the GTPase activity of Ras
      (GAPs) ensure that following mitogenic stimulations, they return to their
      inactive GDP-bound state; amongst these proteins are p120-GAP, neurofibomin (the
      product of the susceptibility gene to type I neurofibromatosis), as well as the
      inositol 1,3,4,5-tetrakisphosphate-dependent GAPIP4BF. Several effectors have
      been identified that mediate the biological effects of Ras. The serine/threonine
      kinase Raf-1, as well as the closely related protein B-Raf, elicit the ERK
      cascade of MAP kinases. Phosphatidylinositol-3-OH kinase is involved in the
      activation of the Rac/Rho family proteins that play a role in the control of
      actin polymerisation, as well as in growth control, RalGDS, RGL and Rlf, are
      responsible for the activation of the Ras-related protein Ral. Recent evidence,
      using effector domain mutants of Ras, demonstrates that these pathways cooperate
      to elicit the growth promoting effects of Ras proteins.

PMID- 9255348
TI  - [Inhibitors of farnesyl transferase in oncology: from basic research to
      pharmaceutical research].
AB  - Advances in medical oncology have been obtained with compounds having new
      structure/mechanism of action. Pharmaceutical research is largely focused on
      "prospective" targets identified by basic science such as the oncogenic signal
      transduction pathways. Ras proteins stand as converging targets that could be
      blocked by different approaches including inhibition of the isoprenylation of the
      proteins. Many academic institutions and pharmaceutical companies have embarked
      on the research of farnesyl transferase inhibitors. Two approaches have been
      developed: 1) random screening of compounds from natural/synthetic origin; 2)
      synthesis of compounds able to mimic the C-terminal tetrapeptidic "CAAX box" and
      to inhibit consequently the critical step of farnesylation. This peptidomimetic
      approach has been successfull since active and specific inhibitors of Ras
      proteins farnesylation have been synthesized in the nM range. However, several
      major drawbacks have been identified: in particular, most of the time, the
      preclinical evaluation has been done with biochemical and biological materials
      implicating the activated Ha-ras oncogene (very unfrequently activated in human
      tumors) instead of the activated Ki-ras oncogene which is the relevant target in
      human carcinomas. This has resulted in the selection of compounds with
      preferential activity on Ha-ras tumors. Nevertheless, evidence has been now
      generated that inhibition of farnesyl transferase of ras proteins can lead to
      significant experimental antitumor effects. The most convincing data are those
      obtained with the Merck inhibitor L739,749 which is able to cause tumor
      regressions of carcinomas in transgenic mice.

PMID- 9255349
TI  - [Ras proteins in Saccharomyces cerevisiae, their partners and their activation].
AB  - Ras proteins play the role of molecular switches by conformational change between
      a GTP and a GDP-bound state. In the yeast Saccharomyces cerevisiae, they are
      encoded by two partially redundant genes RAS1 and RAS2 with a different pattern
      of gene expression. They are essential for growth because they are required for
      the activation of the adenylate cyclase and thus the protein kinase A pathway.
      Other possible biological functions remains to be established. To achieve their
      biological function, they need to be processed after their synthesis, they are
      modified farnesylated and palmitoylated at their C-terminal end at their CaaX
      box. Palmitoylation, involved in membrane localization, is not essential for
      growth but required for glucose signaling whereas farnesylation appears to
      participate in adenylate cyclase activation. In the GTP-bound state ras proteins
      interact through their conserved effector domain with the adenylate cyclase, the
      product of the CYR1/CDC35 gene. They also interact with GTPase activating
      proteins encoded by IRA1 and IRA2. These proteins are specific for yeast ras. It
      has been shown that Ira2p recognizes specific residues of yeast ras not shared by
      mammalian ras. The interaction with the guanine nucleotide exchange factor (GEF)
      of the CDC25 family is enhanced by dominant negative mutations such as RAS2ala22.
      Using the two hybrid approach, we have showed the key role of position 80 in
      Ras2p and confirmed the involvement of the a2 helix, the other switching part of
      ras, in this interaction and the induced effect. As a counterpart we have
      identified positions in HGRF55 conserved in other GEF involved in ras
      interaction. The triggering elements of ras activation: the GEF Cdc25p and Sdc25p
      are limiting components of the ras system. Cdc25p is part of a multimolecular
      complex associated with the membrane. We have shown that it can form homodimers
      and heterodimers with Sdc25p. It is an unstable protein containing a cyclin
      destruction box. Therefore its activity on ras could be regulated by controlling
      its cellular content.

PMID- 9255350
TI  - [Signal transduction by Rac small G proteins in phagocytes].
AB  - Rac1 and Rac2 are 92% homologous cytosolic small GTPase proteins. Both Rac1 and
      Rac2 have been implicated with NADPH oxidase activation in vitro, however, Rac2
      is largely predominant in human phagocytes. NADPH oxidase is a plasma membrane
      enzyme of phagocytes, generating superoxide anions which serve as bactericidal
      agents. Activation of this multimolecular enzyme, minimally requires assembly at
      the membrane with flavocytochrome b258 of cytosolic components p47phox, p67phox
      and Rac proteins. Using the yeast two hybrid system, we provide data
      demonstrating in vivo interactions between human p47phox, p67phox, and Rac
      proteins. Rac proteins interact with p67phox in a GTP-dependent manner, but do
      not interact with p47phox. Moreover, Rac effector site mutants which are known to
      be inactive in NADPH oxidase lose their interaction with p67phox. Finally, we
      observe that p67phox interacts six fold better with Rac2 than with Rac1. We also
      show a strong intracellular interaction between p47phox and p67phox. These
      results indicate that activated Rac, and particularly Rac2, can regulate
      superoxide production by NADPH oxidase of phagocytic cells through direct
      interaction with p67phox subunit. Recently published data suggest that Rac
      proteins could transduce mitogenic signals in non-phagocytic cells through
      superoxide production by a phagocytic-related NADPH oxidase enzymatic system
      which remains to be determined. NADPH oxidase regulation by Rac proteins in
      phagocytes could then be used as a model to understand the molecular mechanisms
      underlying Rac functions in various cell types.

PMID- 9255351
TI  - [Epigenetic mechanisms of aging: relations between Maillard reactions and radical
      generation].
AB  - Aging is under the influence of both genetic and epigenetic factors. We are
      particularly interested in these latter mechanisms which play an important role
      in the aging of most if not all pluricellular organisms. Genetic factors on the
      contrary appear to differ among the species investigated. We studied two major
      epigenetic mechanisms: the Maillard reaction or nonenzymatic glycosylation and
      generation of free radicals. Using a sensitive method of free radical detection
      based on the degradation of hyaluronan, we could show that Maillard products are
      able to produce the depolymerization of this glycosaminoglycan. This may be of
      special importance in tissues rich in hyaluronan as the vitrous of the eye. Its
      degradation with age, accelerated in diabetes may well depend on such reactions,
      intensifyed in diabetes and involved in its complications as diabetic
      retinopathy.

PMID- 9255352
TI  - [Aging and brain circulation. Role of the extracellular matrix of brain
      microvessels].
AB  - Maintenance of normal brain activity is dependent among other factors on the
      maintenance of a functional blood-brain barrier (BBB), localised mainly at the
      capillary wall of cerebral microcirculation. The modifications of the BBB during
      aging play an important role in cognitive decline with aging as well as in
      dementias. A review of the experiments of our laboratory over the last decades is
      presented, on the interaction of endothelial cells with their basement membranes,
      both together representing a functional unit of BBB. The action of proteolytic
      enzymes on the basement membrane increases BBB permeability by increasing the
      transcellular transport activity of endothelial cells. Flavonoid drugs protect
      BBB from proteolytic activity by interacting with collagen fibers and protecting
      sensitive peptide bonds from attack by proteolytic enzymes. These drugs enhance
      also the resynthesis of degraded basement membranes.

PMID- 9255353
TI  - [Prostatic bud induction by brief treatment with growth factors].
AB  - Effects of brief treatment of growth factors on the urogenital sinus of embryonic
      rats were investigated and it was found that 8 hour-treatment in the beginning of
      5-day cultivation with the epidermal growth factor (EGF) or transforming growth
      factor-alpha (TGF-alpha) can provoke prostatic bud formation, in the medium
      deprived of androgens.

PMID- 9255354
TI  - [In vitro effects of free fatty acids on water content and osmotic fragility of
      erythrocytes in rabbits].
AB  - The effects of free fatty acids in the blood on osmotic fragility and water
      content of erythrocytes when combined with hyperthermia were investigated. The
      isotonic buffer, containing the fatty acid, was added to the erythrocyte
      suspension to a final concentration of 200 microM/l. The samples were kept for
      one hour in an incubator at 37 or 42 degrees C. The osmotic fragility of
      erythrocytes was determined by Coil Planet Centrifuge System and intracellular
      water content was measured by gas-liquid chromatography. A high concentration of
      linoleic acid and hyperthermia caused the increase in intracellular water and the
      decrease in osmotic resistance of the red blood cells. The present experiment
      demonstrated that unsaturated fatty acid was one of the principal chemical and
      metabolic factors which cause sports anemia.

PMID- 9255355
TI  - [Anterior spinal fusion by thoracoscopy. A non-traumatic technique].
AB  - PURPOSE OF THE STUDY: Video assisted thoracic surgery (VATS) is a new modality
      which allows visualization of, and access to the intrathoracic organs without
      thoracotomy. Recently, this technique has been used for anterior thoracic spine
      approach to perform surgery which previously required standard postero-lateral
      thoracotomy. The authors report their initial experience of anterior spinal
      fusion using thoracoscopy and give a detailed description of their surgical
      procedure. MATERIAL AND METHODS: This technique, started on June 1993, was
      performed only in one level 1 in 10 patients who had thoracic spine trauma with
      fracture or luxation. The procedure was performed in the lateral decubitus
      position. The patient was prepared in the standard manner for a full thoracotomy.
      Surgical instruments that are needed for conversion to an open procedure must be
      in the operative room. Ventilation was stopped to the ipsilateral lung. Lung's
      collapse of the surgical side was obtained with a double lumen tube. Carbon
      dioxide (CO2) insufflation was used to further collapse. The first thoracoscopic
      portal was placed through the sixth or seventh intercostal space in the posterior
      axillary line, which was the safest place. All subsequent portals were placed
      under thoracoscopic visualization, in a triangular way as recommended by
      Landreneau (1992). Only open trocars were used to avoid complication of CO2
      insufflation. Once the target level has been defined, a needle was placed into
      the disc space and roentgenographic confirmation obtained. The parietal pleura
      was then divided using monopolar electrocautery. Segmental vessels of the
      operation field lied transversely across the midportion of the vertebral body.
      They were mobilised and systematically ligated with endoscopic clip to simplify
      the procedure. Then the intervertebral space was opened and bone and disc were
      removed, restricted to the anterior and middle third. The graft was placed into
      the thoracic cavity by using a high density calcium hydroxyapatite ceramic block.
      Peroperative radiologic control ascertained the good position of the implant. At
      the end of the procedure a chest tube was placed through the lower trocar site
      and the lung re-expanded. A post operative CT Scan controlled good position of
      the graft and complete lung expansion. Contra-indications for VATS are previous
      surgical procedures or empyema causing extensive pleural adhesions. Procedures
      not appropriate for VATS approach are some that require anterior instrumentation
      for stabilisation, burst fracture, or fracture with posterior wall involved.
      RESULTS: The planned procedure was accomplished in all but one patient who
      required conversion to an open procedure because of segmental artery bleeding.
      Mean operative time was 1 h 45 mm, and mean estimated blood loss was 650 cc.
      There was no complication from CO2 insufflation neither postoperative
      complication. With an average of 2 years follow up, anterior grafting is as good
      as an open technique, radiologic evaluation according to Uchida (1990) showed
      good incorporation of each block without any radiolucent line or displacement.
      DISCUSSION: According to literature this technique was performed safely in 10
      cases, especially without any respiratory complications and chronic pain
      (impairement of pulmonary function, re-expansion failure, incisional
      complications, rib fractures, chronic pain and malfunction of the chest wall,
      limitation of shoulder girdle motion) which are considered to be the main
      disadvantage of traditional thoracotomy. Many authors previously used VATS for
      multi level thoracic discectomy for correction of spinal deformities (Mack 1995),
      spinal reconstructive surgery (Mac Afee 1995) or removal of protrude thoracic
      disc (Rosenthal 1994). CONCLUSION: This original technique demonstrates that
      thoracoscopy for anterior thoracic surgery is better for the patients, reducing
      surgical trauma of the chest wall and to the lung parenchyma (in term of post
      operative comfort, sh

PMID- 9255356
TI  - [Sciatica caused by avulsion of the vertebral limbus in children].
AB  - PURPOSE OF THE STUDY: Sciatica is very rare in children. We report a particular
      from due to traumatic avulsion of the posterior vertebral limbus. The purpose of
      this study was to give the principal clinical and radiological aspects of this
      entity and to discuss the treatment which should be different from that of common
      adult disk herniation. MATERIALS: From 1980 to 1992, 10 children were examined
      for a sciatica (7 boys and 3 girls aged from 10 years 1 month to 15 years 2
      months). Sciatica appeared in all cases during sport activities and sometimes
      after a sport accident. Lumbar spine stiffness was encountered in all cases.
      Radiculalgia was unilateral in 7 cases, bilateral in 3 cases, in L5 territory in
      3 and S1 in 7 cases. 4 children had deficitary neurological signs: 3 abolitions
      of achilles reflex, 1 weakness of foot dorsi-flexors. Standard x-rays showed in 4
      cases the avulsed fragment in the vertebral canal. Spondylosis was encountered in
      3 cases and spondylolisthesis in one case. Diagnosis was possible in all cases
      with CT Scan, M.R.I., when done showed a normal disk signal. Three children were
      managed by a conservative treatment by rest or brace. Seven had a surgical
      treatment: resection of the avulsed fragment in 6 and total diskectomy in one.
      The mean follow-up was five years (2 to 8 years). RESULTS: There was no
      complication. At last follow-up all children had a good result without sciatica
      recurrence. DISCUSSION: Many factors allow us to think that avulsion of the
      vertebral rim in children is of traumatic origin. CT Scan is the best exploration
      for this particular lesion. It enabled evaluation of fragment volume and
      location. Magnetic resonance imaging showed uninjured disks. Removal of the
      avulsed fragment without diskectomy seems possible in children.

PMID- 9255357
TI  - [A prospective study of the outcome of anterior laxity of the knee after anterior
      cruciate ligament reconstruction with procedures using two different patellar
      tendon grafting methods].
AB  - PURPOSE OF THE STUDY: The aim of this study was to evaluate postoperative
      evolution of anterior laxity, in order to know at what time the elongation of the
      reconstructed anterior cruciate ligament (ACL) begins to develop after surgery,
      and if there were any correlations with recuperation of knee flexion or
      extension. The second purpose of this study was to compare two series of patients
      operated on by two different procedures for a long standing ACL rupture. MATERIAL
      AND METHODS: Two series of patients were compared: group I (60 cases), had an ACL
      reconstruction using a free autologous patellar tendon graft with a bone-to-bone
      fixation, supplemented by an external extra-articular plasty with a strip of
      quadricipital tendon as a direct prolongation of the graft of the patellar tendon
      and patella itself. "Mac InJones", and group II (50 cases), had a reconstruction
      with a similar transplant, but still attached on the tibia and with a fibrous
      fixation through the femoral condyle and the Gerdy's tubercule (modified
      "Marshall-Mac Intosh"). Anterior laxity was measured using two instrumented
      methods; first, Medmetric knee arthrometer (KT-1000), before and after operation,
      then each month later during the first 6 months and yearly. On the other hand, a
      personal stress X-ray protocol (at 20 degrees of flexion and with application of
      a 9 kg load at the distal part of the thigh), was made before operation, 6 months
      later, and yearly during 8 years. The laxity of both medial and lateral
      compartments of the knee were separately measured. Laxity was studied in parallel
      with the recuperation of knee flexion and extension during a rehabilitation
      program without any limitation in both directions. RESULTS: During a period of 3
      months, the laxity was arthrometrically inferior to the normal knee in the two
      groups, and appeared progressively. Laxity was independent from early
      recuperation of full range of flexion and extension. The elongation of the
      reconstructed ligament was showed to develop during the first 6 months and less
      during the following 6 months. Better results were found for group I during the
      earliest period with the Medmetric arthrometer, but there was no difference
      between both groups after 1 year and 2 years. With dynamic radiography, laxity
      was higher than indicated by KT-1000, and results were better for group I. Laxity
      was stabilized after one year and the results were still good after 8 years.
      DISCUSSION: KT-1000 showed a great interest for measurement of the compliance
      index (difference between laxity at 89 newtons and 69 newtons of traction), and
      can be used without any inconvenient for patients. Stress radiographs may be used
      for yearly controls. The radiographic method had better accuracy than KT-1000 and
      gave precise laxity measurements of the medial and lateral compartments of the
      knee. The laxity of the medial compartment showed to have a good prognostic
      value. CONCLUSION: Evolution of laxity is more favourable in group I with bone-to
      bone ligament fixation. Recovering early and complete flexion and extension is
      not prejudicial for the ligament. Laxity developed between 3 and 6 months and
      less between 6 and 12 months. KT-1000 is able to detect laxity during early
      postoperative period. Dynamic radiographs are more precise to control laxity year
      after year. Informations concerning the two compartments of the knee are of great
      interest to compare different procedures and to improve new surgical techniques.

PMID- 9255358
TI  - [Comparison between magnetic resonance imaging and arthroscopy for the diagnosis
      of knee meniscal lesions].
AB  - PURPOSE OF STUDY: The authors evaluated the use of MR-imaging of the menisci
      compared to arthroscopy considered as the gold standard by which all noninvasive
      imaging procedures of the knee have to be measured. MATERIAL AND METHODS: In a
      prospective study, we evaluated the use of MRI in 50 patients with clinically
      suspected disorders of the meniscus, followed by an arthroscopic examination by
      an experienced arthroscopist. MRI studies were performed after clinical
      evaluation and were interpreted by an experienced radiologist, who had no
      knowledge of the clinical findings. RESULTS: The accuracy of the diagnosis from
      MRI was 78 per cent for the medial meniscus (sensitivity 79 per cent and
      specificity 78 per cent) and 94 per cent for the lateral meniscus (sensitivity 50
      per cent and specificity 98 per cent). The average age of the patients was 34
      years, with a range from 3 to 73 years. The imaging studies revealed 9 false
      positive test and suggested that the meniscus was either degenerated or form in
      the horizontal plane. In all 9 menisci the abnormal MR imaging signal was limited
      to the posterior horns. The positive predictive value was 59 per cent and the
      negative predictive value was 94 per cent representing a moderate level of
      diagnostic certainty, both in patients who had a positive result and in those who
      had a negative result. High predictive negative value of MRI indicates that a
      negative MRI is quite reliable for meniscal lesions. DISCUSSION: Problems of MR
      imaging are the popliteus tendon sheath and the transverse ligament. This
      ligament is seen in association with a large branch of the lateral inferior
      geniculate artery, and may be mistaken for a grade 3 signal intensity in the
      anterior horn of the lateral meniscus. CONCLUSION: A normal MRI allows to
      eliminate a meniscal lesion and so there is no need for a diagnostic arthroscopy.
      But with a pathologic MRI there is a risk to establish too often the diagnostic
      of a meniscal lesion rather then to identify structural modifications as a
      degeneration.

PMID- 9255359
TI  - [Biomechanical comparative study of three types of osteosynthesis in the
      treatment of supra and intercondylar fractures of the humerus in adults].
AB  - PURPOSE OF THE STUDY: Supra and intercondylar fractures are the most common
      fractures of the distal end of the humerus in adult. An osteosynthesis consisting
      of a plate is the treatment of choice. But location and type of plate always
      remain open for debate. The authors present the results of an in vitro
      biomechanical study, which compared the stiffness of three types of
      osteosynthesis commonly used in these fractures. MATERIAL AND METHODS: The
      devices were on one hand the premolded lateral plate of Lecestre and Dupont
      (Howmedica) used alone or in conjunction with a medial 1/3 tubular plate of the
      AO group, and on the other hand a posterior plate, of which we are developing a
      new model, the Lambda plate (Protek) "Y"-shaped, monoblock, flat and molded on
      the humerus during operation. The study compared these different methods of
      fixation on fresh human humeri. In a first part, the posterior plate was compared
      to the single lateral one; in a second part, the posterior plate was compared to
      the coupled lateral and medial plates. The three plates were made of identical
      material. Both studies used eight pairs of bones with supra and intercondylar
      fractures realized by sawing. Each bone of a pair was fixed with one of the two
      types of device. Each humerus underwent different loading forces; sagittal
      bending (anterior and posterior) and torsion. The displacements were recorded
      using a calibrated measuring device coupled to two displacement sensors. The
      stiffness was calculated on force/displacement curves. RESULTS: In anterior
      bending, the Lambda posterior fixation was significantly stiffer than the single
      lateral one (p < 0.05) (239 +/- 109 versus 129 +/- 65 N/mm), and was not
      significantly different of the bilateral fixation (229 +/- 93 versus 224 +/- 108
      N/mm). In posterior bending, the mean stiffness of the Lambda fixation was not
      significantly different to that of the lateral fixation (91 +/- 27 versus 91 +/-
      52 N/mm), and less than that of the bilateral one (130 +/- 39 versus 170 +/- 70
      N/mm), but not significantly. In torsion the mean stiffness of the Lambda
      fixation was superior to that of the lateral one (146.75 +/- 50.66 versus 119.75
      +/- 58.8 Nm/rad), and bilateral one (233.31 +/- 107.47 versus 212.31 +/- 113.55
      Nm/rad), but again not significantly. DISCUSSION: The ideal osteosynthesis for
      the fractures of the humeral distal doesn't exist, because the bone undergoes
      antero-posterior and posteroanterior cyclical forces during elbow flexion.
      Therefore the best device should be placed on both sides of the bone, but
      anatomical reasons make this location impossible. According to our study, we
      think the "less worst" device is the posterior one using the Lambda plate. Its
      symmetrical design allows a best loading distribution on the two columns. Its
      thickness compensates for its posterior location and the short interval between
      two holes allows to put many screws (4 to 6) into the epiphysis. All supra and
      intercondylar fractures, comminuted or not, can be treated with this material.
      The single lateral device isn't still enough. Its stiffness mainly depends on the
      orientation of the oblique screw in the medial column. But the design of this
      column doesn't always allow for an optimal location of the screw, which is the
      reason of several failures. The bilateral device gives a stiffness, comparable to
      the posterior one, but doesn't allow as many screws as the Lambda plate in the
      epiphysis. Therefore, it can't be used in very distal fractures. CONCLUSION: In
      spite of the progress of the material and the accuracy of the indications, the
      treatment of supra and intercondylar fractures of the distal end of the humerus
      is always a difficult problem. The devices have to be as stable as possible to
      allow an early motion. The best one should be placed on both sides of the distal
      humerus, because of the sagittal cyclic forces it undergoes, but this location is
      anatomically impossible. Our study concludes that the device using the Lambda
      plate i

PMID- 9255360
TI  - [Evaluation of impaction on bone nail and bone plate of the pertrochanteric
      fracture].
AB  - PURPOSE OF THE STUDY: Impaction in pertrochanteric fracture sites is a well known
      phenomenon; the screw-plate system is designed to stabilise the fracture.
      Although easier to use, the risk with the nail-plate system is postoperative
      penetration of the nail into the joint. The present study was conducted to
      determine the exact conditions of the impaction, and to identify possible ways to
      improve the nail-plate system. MATERIAL-METHOD: The study included 129 cases of
      pertrochanteric fracture, excluding sub-trochanteric fractures. All fractures
      were fixed with a 130 degrees angulated nail-plate. In all cases, consolidation
      was uneventful after 8 to a 12 weeks. The anatomical type of fracture, i.e.
      stable or unstable, was determined according to the size of the intermediary
      fragment, including the trochanter minor. The displacement was measured as the
      difference between the length of the nail and the length of the femoral head and
      neck measured along the axis of the femoral neck. The parameters examined were:
      fracture stability degree, bony mineralisation (Singh Index), nail length,
      femoral neck, length nail position in the femoral head, and above all, fracture
      reduction. All these parameters were computerised and compared using Stat View
      statistics software. RESULTS: Impaction was observed in 43 per cent of cases.
      Among these, 25 per cent were rated as slight (1 to 5 mm), 18 per cent as
      moderate (over 5 mm) and 9 per cent as marked (10 to 25 mm). Impaction was
      associated with demineralisation of the bone tissue (p = 0.001). The anatomical
      classification of the fracture was not a determining factor (p = 0.19), as marked
      displacements were also recorded in stable fractures. A posterior and inferior
      position of the intramedullary nail in the femoral head is one of displacement
      determining factors (p = 0.004, two-sided 1 test). Valgus over-correction is the
      most important factor, especially when it is associated with bony
      demineralisation (p = 0.02) and an inadequately centred intramedullary pin (p =
      0.02). Shorter the femoral neck, and shorter the nail, greater was the frequency
      of nail articular penetration. DISCUSSION: The risk of articular penetration
      therefore reaches 15 per cent in petrochanteric fractures repaired with a nail
      plate, set at an angle of 130 degrees. A short neck, a cervicodiaphyseal angle
      superior to 140 degrees, and demineralisation are the three determining
      parameters. Stable or unstable fracture has in fact little effect on displacement
      incidence, and therefore does not, on its own, warrant the use of a prosthesis in
      comminuted fractures. The authors compared their results to literature on
      progressive sliding system: the incidence of complications associated with this
      type of fracture treatment is identical, but the determining parameters are
      different. CONCLUSION: The study shows that the nail-plate is efficient and
      provides simple and solid fracture fixation. However, this osteosynthesis
      material needs to be modified in order to improve its fixation in the femoral
      head.

PMID- 9255361
TI  - [Value of orthopedic treatment of distal fractures of the forearm in children.
      Apropos of 152 cases].
AB  - PURPOSE OF THE STUDY: Distal forearm fractures in children are frequent.
      Management is conservative except in rare cases which will be discussed. MATERIAL
      AND METHODS: Retrospective analysis of 152 distal forearm fractures after 10 and
      a half months (6 to 48 months) of follow-up was carried-out. Age ranged from 2 to
      16 years (mean 10 years). Orthopaedic treatment was proposed in each case, but in
      5, surgical treatment was required at onset. Clinical and radiological fracture
      reduction analysis was conducted immediately post op and during follow-up. 92 per
      cent of these fractures had a posterior or posterolateral angulation (with a mean
      angulation of 28 degrees 5). Among these cases, 64 per cent had instability
      criteria. Degree of translation when present (79 cases) was at 100 per cent in 55
      cases (70 per cent); greater than 50 per cent in 11 cases (14 per cent) and less
      than 50 per cent in 13 cases (16 per cent). In 12 cases (8 per cent), the
      displacement was anterior with a degree of translation greater than 50 per cent
      in 6 cases and an angulation always greater than 30 degrees in the 6 remaining
      cases. RESULTS: In 5 cases, surgical treatment was necessary due to initial
      instability and/or irreducibility. In 147 cases, analysis of instability
      criteria, reduction and cast quality, and of fracture location showed
      displacements in cases of non-adapted and incorrect X-ray work up (6 cases of 6);
      in 18 cases of 24 when the cast was adapted but with incorrect X-ray work-up; in
      5 cases of 10 when the cast was non-adapted with correct X-ray work-up, in 3
      cases of 7 when the fracture was superiorly located; and in 6 cases of 6 when
      cast was prematurely opened. DISCUSSION: Close reduction is possible for
      fractures with large displacement but must be done perfectly and the cast must be
      adapted. If instability, irreducibility and/or incorrect reduction exist,
      management must include posterolateral and intrafocal percutaneous pinning,
      especially in older children. While rare, this indication must be known.

PMID- 9255362
TI  - [Contribution of electromyographic analysis of the walking habits of children
      with spastic foot in cerebral palsy: a preliminary study].
AB  - PURPOSE OF THE STUDY: This preliminary study describes the methodology and the
      results of gait analysis in cases of equinus and equino-varus deformity of the
      foot in cerebral palsy children. The ultimate goal was to establish an aid to
      decision in spastic foot surgical management. MATERIAL: A prospective series of
      12 walking children (16 feet) with cerebral palsy has been evaluated prior to
      surgical correction of equinus or equino-varus deformity of the foot. The mean
      age was 8 years (range 4 to 11 years of age). METHOD: The pattern of muscle
      activity during gait cycle has been recorded by surface electrodes for the
      tibialis anterior, the triceps and the peroneae and by implanted electrodes for
      the tibialis posterior. Foot switches have been used to differentiate swing and
      stance gait phases. The results were compared with these of a series of normal
      children previously published. RESULTS: In four cases, the dynamic equinus was
      due to an extended or continuous contraction of the triceps surae. The varus
      deformity appeared to originate from two muscles: the tibialis posterior in 9
      cases and the tibialis anterior in 1 case. Both muscles were responsible for the
      deformity in 2 cases. Two muscular activation patterns were observed in the
      tibialis posterior: inverted (2 feet) or permanent (9 feet). From the main muscle
      which was responsible for deformity, we have determined the surgical technique
      which was most appropriate to restore the muscular balance. DISCUSSION: Our
      observations confirm Perry's hypothesis, namely that selective and phasic control
      during the walking cycle does not occur for patients suffering from cerebral
      palsy. Different surgical procedures were chosen according to the literature on
      this subject. In the treatment of equinus deformity, lengthening of the Achilles
      tendon is a satisfactory technique for hemiplegic patients. But we prefer
      gastrocnemius recession described by Vulpius in spastic diplegia in order to
      avoid over-lengthening or calcanal gait. If it can be shown that posterior tibial
      muscle overactivity is the cause of equinovarus, we perform a posterior tibial
      tendon lengthening, as proposed by Ruda and Frost, or a split posterior tibial
      tendon transfer as developed by Green. If the posterior tibial muscle is active
      only during the swing phase, we accomplish a split posterior tibial tendon
      transfer through the interosseus membrane as advocated by Saji. If the anterior
      tibial muscle is continuously active, a split anterior tibial tendon transfer to
      the cuboid described by Hoffer is performed. If the activity is continuous in
      both the tibial posterior and the tibial anterior muscles, we add a posterior
      tibial myotendinous lengthening to the split anterior tibial tendon transfer.
      CONCLUSION: Since 1992, we have developed in our institution a gait analysis
      laboratory in order to bring objective data in the process of decision making for
      tendon transfer surgery. With 4 years experience, this objective support now
      seems to us compulsory in decision of type of transfer. The goal of this
      preliminary study was to explain how we use the data and match these to our
      experience and literature.

PMID- 9255363
TI  - [Scaphoid and lunate palmar divergent dislocation. Apropos of a case].
AB  - A case of palmar dislocation of the scaphoid and lunate which where dissociated
      from each other is reported with a 3.5 years follow up. A 32 years old man fell
      while reading his motorcycle. He landed on his left hand dorsiflexed. There was
      no skin dilaceration and neuro-vascular status of his hand was intact. X-rays
      showed a palmar dislocation of the scaphoid and lunate with a large gap between
      the two bones. The lunate was also completely dissociated from the triquetrum and
      the capitate. Distal pole of the scaphoid remained in contact with the trapezium.
      The patient was taken to the operating room, and after unsuccessful closed
      reduction, an open reduction through a palmar approach was performed. A complete
      disruption of the anterior capsule was founded and all perilunate ligaments were
      completely disrupted. Reduction was easy under direct vision, and the anterior
      capsule was repaired. A non displaced trapezium fracture seen at surgery was
      fixed with a Kirschner wire. A long arm cast applied for 6 weeks. At 3.5 years
      follow-up, the patient had an almost full range of motion and no residual pain.
      Power grip was 25 per cent reduced in comparison with the opposite side. X-rays
      showed a palmarflexed scaphoid and Magnetic Resonance imaging showed no evidence
      of avascular necrosis. DISCUSSION: Simultaneous dislocation of scaphoid and
      lunate as a unit or with a large gap between the two bones are extremely rare
      injuries. In all cases already reported, results were briefly presented without
      any available clinical and radiological data because patients were lost for
      follow-up. In our case report, the anatomy and kinematics of the wrist showed the
      lack of our initial treatment with a single volar approach, anterior capsular
      reparation and a long arm cast alone. In fact, at 3.5 years follow up,
      ligamentous healing was inadequate to control compressive forces across the wrist
      and the scaphoid volarflexed despite a good alignement in the cast. Although the
      functional results is good, radiological outcome is far from being good. This
      case demonstrated that even in early treatment with a good position of carpal
      bones in the sole cast, healing of the ligamentous system without loosing
      reduction is difficult. CONCLUSION: In such a case, and with a low rate of
      avascular necrosis in perilunate dislocations treated early we suggest an open
      reduction and internal fixation (O.R.I.F.) to prevent carpal instability. We
      recommend combined volar and dorsal approaches for repairing anterior and
      posterior ligaments (especially interosseous ligaments on both sides of the
      lunate), associated with a stabilization of the entire carpum by scapho-lunate,
      triquetro-lunate, and capito-lunate Kirschner wire fixation.

PMID- 9255364
TI  - [A propos of an unusual case of lumbar-pelvic dislocation in a suicidal jumper].
AB  - PURPOSE OF THE STUDY: We report a particular case of lombo-pelvic dislocation in
      a suicidal jumper, characterized by a distal sacral fracture associated with
      bilateral fractures of both iliac wings. To our knowledge, it has yet not been
      described. MATERIAL AND METHODS: The patient was a 27 years old individual. On
      admission, he sustained the following injuries: hemodynamic shock with
      intraperitoneal bleeding due to disruption of the triangular ligament of the
      liver, which resolved with blood transfusions and did not require surgical
      treatment pelvic fractures initially identified as transverse fractures of both
      iliac wings, with bilateral avulsions of sciatic spines a compression fracture of
      the first lumbar vertebra without neurologic complication. In the intensive care
      unit, evolution was favorable. However, an incomplete cauda equina syndrome was
      noticed: the anal sphincter was flacid but perianal sensation to pinprick was
      conserved. An electromyogram showed that the latence of perineal reflexes was
      increased. The fracture and its displacement were recognized secondarily. A
      pelvic C.T. exhibited an increases in the antero-posterior dimension of the
      pelvic ring, due to a distal-displaced transverse sacral fracture. The proximal
      fragment of the sacrum remained attached to the iliac wing since sacro-iliac
      joints were intact, iliac wings had tilted forward, and the distal tip of the
      proximal sacral fragment was driven backward and inferiorly. RESULTS: The patient
      was maintained in the supine position during 3 months. He then rapidly recovered
      normal function of his lower limbs. He had normal gait patterns and pelvic
      static. He did not complain of any pain. Finally, the neurological deficit
      disappeared and he regained full sexual function and complete control of
      micturition. DISCUSSION: We think that this fracture should be considered as a
      variety of suicidal jumper's fracture described by Roy Camille et al. It has the
      same displacement as type 2 fracture in Roy Camille classification. In the
      emergency room, diagnosis is difficult, based on usual AP pelvic roentgenograms.
      A bilateral fracture of iliac wings in a suicidal jumper, especially if
      associated with bilateral sciatic spine avulsions, is an indication to a pelvic
      C.T.. A neurological perineal deficit should be ruled out. In our case, the
      perineal deficit can be attributed to the stretching of sacral roots resulting
      from a posterior displacement of the sacrum. The favorable evolution suggests
      that surgery may be not required, and there is no evidence in the literature that
      it would help neurological recovery. In distal fractures, the sacral canal is not
      narrowed, and a sacral laminectomy appears therefore not indicated. CONCLUSION:
      We have described a particular type of transverse fracture of the pelvis, which,
      in our mind, should be put in the same category as type 2 transverse fractures of
      the sacrum described by Roy Camille and al, in the suicidal jumper. Since there
      is no compression of sacral roots into the sacral canal, prolonged bedrest is
      likely to be the better treatment.

PMID- 9255365
TI  - [A rare entity: intraosseous synovial cyst of the calcaneus].
AB  - The authors report a rare case of a histologically proven intraosseous ganglion
      found in the calcaneus. A 59 year old carpenter was referred to our institution
      because of progressive talalgia with swelling of the hindfoot, increasing with
      prolonged standing and walking at job. X rays showed a multilobular radiolucent
      cyst developed in the anterior part of the left calcaneus, outlined by a rim of
      sclerotic bone. A lateral cortical split revealed by CT was deemed to be a
      traumatic communication with the soft tissue. At biopsy, a gelatinous and hematic
      content was noted but pathologic examination of the cyst walls failed to reveal
      the diagnosis; there were no malignant cells. 5 weeks later, the cyst and its
      contents were excised through lateral approach and the defect filled with
      cancellous bone graft. At pathological examination, a final diagnosis of ganglion
      cyst was determined. One year after surgery, the patient was asymptomatic; no
      sign of recurrence was observed. Intraosseous ganglia are benign subchondral
      cysts which rarely involve foot bones. When pain becomes consistent and swelling
      occurs because of overlooked fracture, malignant bone tumors should be ruled out.
      Histological examination is mandatory to confirm the diagnosis. Excision of the
      cyst and bone grafting are effective; recurrence is infrequent.

PMID- 9255366
TI  - [Intramuscular myxoma. Apropos of two cases].
AB  - The authors report two cases of rare localization of intra muscular myxoma: one
      in the buttock, and the other in the lumbar area. The first case, a 58 years old
      woman had a four month history of a mass in the buttock. Computed tomography
      revealed the presence of a solid tumor. Diagnosis was based on histological
      examination. After surgical treatment no recurrence was observed after fourteen
      months. The second case was a 54 years old woman who presented a sciatica with
      back pain and neurological signs. The symptoms didn't response to medical
      treatment. Computed tomography showed an enlarged and-cystic lumbar lesion
      extending to the first sacral hole, with bone erosion of L3 and L4 articular
      apophysis and spinous process. Needle biopsy and surgical excision of the tumor
      were performed. Total neurological recovery was observed and no recurrence was
      observed after three years. The authors reminded the characteristics of this rare
      and benign soft tissue tumor and specified the place of magnetic resonance
      imaging (MRI) to establish the diagnosis which was still confirmed by
      histological examination of an open biopsy. Clinical follow-up revealed
      exceptional recurrence and no metastasis.

PMID- 9255367
TI  - [Segmental sternal dislocation in children. Apropos of a surgically treated
      case].
AB  - The authors report one operated case of traumatic sternal segmental dislocation
      in a child, and propose a mechanism for this uncommon lesion. A fourteen year old
      boy was admitted in emergency for anterior chest pain, occurring during an
      exercise in parallel bars without any fall. X ray showed traumatic dislocation of
      the upper sternal segment. After 12 hours, because of bad clinical tolerance
      (pain, dyspnea with sweats and disphagia) reduction and plate stabilization
      (Senegas plate) was performed with immediate pain relief. The boy returned to
      school after 10 days. Plate was removed two months later after healing, with good
      clinical and radiological results. According to rare published cases,
      conservative treatment can be proposed in very young children because of
      dislocation remodeling. By others, in case of bad tolerance, surgical treatment
      is suggested despite the inconvenient of device's removal. The originality of
      this case is the indirect lesion mechanism. Hypothesis is given by authors.
      Treatment by plate is easy and gives immediate pain relief with good clinical and
      radiological results in teen-agers.

PMID- 9255368
TI  - [Bone metabolism during pregnancy and breast feeding. Osteoporosis in pregnancy].

PMID- 9255369
TI  - [Comparison of efficacy and tolerability of a thrombolytic treatment with rt-PA
      in acute massive pulmonary embolism in the elderly and patients under 75 years of
      age].
AB  - BACKGROUND: Pulmonary embolism often occurs in elderly patients. However,
      clinical presentation and treatment of massive pulmonary embolism (PE) in the
      elderly have not been extensively investigated. We report the results of rt-PA
      bolus infusion in patients aged 75 years or more suffering from massive PE.
      METHODS: Fifty-four adult patients referred to our institution with symptoms
      suggestive of massive PE were included in a therapeutic trial of single-chain rt
      PA. Patients with a Miller angiographic score of at least 20/34 were considered
      for entry into the study. Patients were divided into two groups according to
      their age. Clinical presentation at admission, resolution of scintigraphic
      vascular obstruction, death rate, hemorrhagic complications, recurrent pulmonary
      embolism and long-term follow-up were compared between both groups. RESULTS:
      Twenty-eight patients were less than 75 years old and 26 patients were aged 75
      years or more. Clinical symptoms at admission were similar in both groups. The
      mean absolute improvement in the lung scan perfusion defect, the rate of major
      bleeding, and the long-term evolution were not statistically different between
      older and younger patients. CONCLUSION: Clinical presentation and tolerance of
      massive PE did not differ between elderly and non-elderly patients. Old age
      should not preclude thrombolytic therapy in massive PE, provided there are no
      other contraindications for thrombolytic treatment.

PMID- 9255370
TI  - [Systemic scleroderma and cancer. Search for predictive factors of cancer in 123
      patients with scleroderma].
AB  - Several studies have suggested an increased risk of cancer in patients with
      systemic sclerosis, but the potential risk factors for these cancers remain
      unknown. The aim of this study was to identify, among patients with systemic
      sclerosis, factors associated with the development of cancer, with attention to
      clinical (age, sex, cutaneous sclerosis), immunological (antinuclear antibodies,
      anticentromere antibodies, anti-Scl-70 antibodies) and histological (pulmonary
      fibrosis) features. We retrospectively studied 123 patients with systemic
      sclerosis. The median follow-up period was 4 years. Fourteen cases of cancer
      (11.3%) were found (lung n = 3, breast n = 2, ovarian n = 2, skin n = 1, thyroid
      n = 1, rectum n = 1, uterine cervix n = 1, larynx n = 1, pancreas n = 1,
      myelodysplasia n = 1). The characteristics of systemic sclerosis were similar in
      patients with and patients without cancer. Yet, the three cases of lung cancers
      occurred in association with CREST syndromes and anticentromere antibodies.

PMID- 9255371
TI  - [Normal phosphorus and calcium metabolism during pregnancy and breast feeding].
AB  - Calcium homeostasis is stressed considerably during pregnancy and lactation.
      Important regulatory mechanisms are needed both for meeting the fetal requirement
      for calcium and for protecting the maternal skeleton from excessive resorption.
      For the past 10 years, more and more publications have deal with the involved
      mechanisms of regulation. The authors have reviewed these publications and tried
      to answer important questions: is there some irreversible bone loss related to
      pregnancy and/or lactation? How can such bone loss could be prevented?

PMID- 9255372
TI  - [Pathological phosphorus and calcium metabolism during pregnancy and breast
      feeding].
AB  - The occurrence of calcium and vitamin D deficiencies is enhanced during pregnancy
      and lactation. The presentation of parathyroid diseases is altered during
      gestation. A peculiar form of osteoporosis, pregnancy-associated osteoporosis,
      may be observed. Fetus and newborns suffer the consequences of all these
      disorders. The authors have reviewed the early detection and treatment of these
      diseases and emphasized their prevention.

PMID- 9255373
TI  - [POEMS syndrome].
AB  - POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly,
      Endocrinopathy, Monoclonal component and Skin changes). Other various clinical
      and biological features are reported: edema, cachexia, microangiopathic
      glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis.
      Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is
      sometimes associated with lymphoproliferative disorder. Castelman-like disease is
      frequently observed as pathologic findings on lymph nodes. Distinction between
      POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal
      protein is modest-always less than 30 g/L-and is almost of the lambda light chain
      class. In contrast to multiple myeloma this syndrome is rarely associated with
      hypercalcemia, skeletal fracture, renal involvement and increasing of M component
      during evolution. Bone marrow plasmocytosis is usually less than 15% and the
      kinetic phenotype and genetic characteristics of the plasma cell remain those
      found in monoclonal gammopathy of undetermined significance. The pathophysiology
      of this syndrome remains largely unknown but overproduction of pro-inflammatory
      cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical
      manifestations seem to be cytokine related. Polyneuropathy and cachexia are the
      main cause of death. A part corticosteroid and cure of solitary bone lesion,
      treatment is disappointing and survival is 60% at five years.

PMID- 9255374
TI  - [Actinomyces meyeri disseminated actinomycosis disclosing pulmonary carcinoma].
AB  - The diagnosis of severe actinomycosis parallel to that of neoplasia leads to
      speculation of a possible fortuitous association. Because underlying conditions
      such as immuno-suppression are suspected in such disease, and to strengthen this
      hypothesis, we report one more case of disseminated actinomycosis associated with
      a malignant disease, namely an epidermoid pulmonary carcinoma. The diagnosis was
      made by thoracotomy a few months after the infectious episode. Two years later
      the patient recovered. The analysis of the literature data is in favor of a
      fortuitous association between both diagnoses.

PMID- 9255375
TI  - [Spontaneous rupture of the esophagus (Boerhaave syndrome) in a patient with
      scleroderma treated by continuous ambulatory peritoneal dialysis].
AB  - Esophageal involvement is a common situation found in 50 to 80% of patients with
      scleroderma, but Boerhaave's syndrome is rare in this context. The authors report
      the first case of spontaneous esophageal rupture occurring in a chronic renal
      failure patient treated by continuous ambulatory peritoneal dialysis. In this
      observation, sclerodermal esophageal dyskinesia, chronic renal failure which is a
      classical cause of vomiting and the peritoneal dialysis which play an increasing
      role in the intraabdominal pressure are potential contributing factors to
      Boerhave's syndrome. In such patients presenting risk factors, even if they are
      asymptomatic, it seems reasonable to propose esophageal explorations with
      manometry or/and endoscopy looking for dyskinesia or other complications of
      gastro-esophageal reflux.

PMID- 9255376
TI  - [Osteoporosis in pregnancy: apropos of 2 cases].
AB  - Two women, 31 and 19 years old, developed acute back pain with non-traumatic
      vertebral fractures one month after delivery in one case, and during the 9th
      month of gestation in the second case. For the first patient, the evolution was
      favorable with an increase of bone mineral density (15.2% over fourteen months
      under calcium and vitamin D). Ten years later, the osteoporosis of the second
      patient worsened without any new pregnancy. Our observations suggest the
      possibility of different pathogenies in pregnancy-associated osteoporosis.

PMID- 9255377
TI  - [Severe pulmonary manifestation in adult-onset Still's disease].
AB  - Adult onset Still's disease may sometimes be complicated by severe
      manifestations. We report here a case of adult Still's disease with acute
      respiratory failure requiring mechanical ventilation.

PMID- 9255378
TI  - [Spinal cord compression of sarcoidosis origin: a case].
AB  - This observation reports the case of a rapid paraparesia occurring in a young
      man. Imaging disclosed a spina tumor. Diagnosis of sarcoidosis leads us to
      suspect a specific spinal granuloma involvement and to start corticosteroid
      pulses. Clinical and radiological symptoms improved dramatically.

PMID- 9255379
TI  - [Diffuse condensing osteopathy].

PMID- 9255380
TI  - [Perihepatitis and strong lupus anticoagulant. Apropos of a case].

PMID- 9255381
TI  - [Early cerebral ischemic complication following corticotherapy for Horton
      disease].

PMID- 9255382
TI  - [Gallium scintigraphy disclosing tumor of the small intestine!].

PMID- 9255383
TI  - Immunohistochemical study of merosin-negative congenital muscular dystrophy:
      laminin alpha 2 deficiency in skin biopsy.
AB  - We studied the immunohistochemical expression of laminin subunits alpha 2, alpha
      1, beta 1 in muscle and skin biopsy samples from three patients with congenital
      muscular dystrophy (CMD), and from ten control patients investigated for various
      neuromuscular disorders. Merosin alpha 2 chain was not detectable in the basement
      membrane of muscle fibers, or in the nerve endings, cutaneous nerves, and corium
      in the skin of the CMD patients, whereas it was clearly expressed in the skin
      biopsy samples from control patients, especially in the nerve endings of the
      arrector pili muscles. Laminin alpha 1 chain was expressed in the corium, in the
      muscle fiber membranes of arrector pili muscles and in cutaneous nerve fibers,
      perineurium and blood vessels in controls and in CMD patients. Laminin beta 1
      chain was faintly expressed in the corium, and a diffuse labeling was detected on
      arrector pili muscle with enhanced expression at nerve endings, intracutaneous
      nerves and capillaries, with similar findings in all biopsy specimens. For
      merosin-negative CMD patients, skin biopsy may provide a diagnostic alternative
      to muscle biopsy since merosin deficiency can be demonstrated in the skin neural
      structures, and in particular in the nerve endings of the arrector pili smooth
      muscles.

PMID- 9255384
TI  - Ultrastructural changes in rat locus coeruleus induced by chronic opioids.
AB  - The locus coeruleus (LC) is a major noradrenergic nucleus in the brain. The
      activity of the LC neurons is chronically regulated by opioids. So far, very
      little is known about the morphological changes induced by chronic treatment with
      opioids. In the present study, the effects of chronic treatment with morphine and
      dihydroetorphine, a new narcotic analgesic with lower physical dependence
      potential than morphine, were investigated on the ultrastructure of the rat LC.
      Rats received saline or increasing doses of morphine or dihydroetorphine for 5
      days by twice daily subcutaneous injections. Withdrawal was precipitated in half
      of the opioid-treated rats by a single intraperitoneal injection of naloxone 4 h
      after the last injections of opioids. The ultrastructure of the LC was examined
      by electron microscopy. Results showed that chronic morphine treatment induced a
      marked injury to the LC neurons. The primary changes in the cell body were the
      indentation of nuclei, the fragmentation and degranulation of rough endoplasmic
      reticulum, as well as the disaggregation of polyribosomes. Myelinoid bodies were
      seen in the processes. An accumulation of presynaptic vesicles was observed in
      some of the terminals which formed synaptic junctions with the LC neurons as
      compared to the normal controls. Naloxone-precipitated withdrawal from morphine
      did not stop the morphine-induced injury on the LC neurons except that less
      accumulation of presynaptic vesicles occurred. Chronic dihydroetorphine treatment
      only induced a slight change in the ultrastructure of the LC neurons. These
      results indicate that the LC neurons are more vulnerable to chronic treatment
      with morphine than to that with dihydroetorphine.

PMID- 9255386
TI  - Age-related neuronal loss in the nucleus centralis superior of the rhesus monkey.
AB  - The effect of age on the number of neurons in the nucleus centralis superior
      (NCS) was determined in 11 behaviorally tested rhesus monkeys of 7-32 years of
      age, There was a significant age-related decrease in both cell packing density
      and in the total number of neurons. This decrease in number of neurons appeared
      to effect two different populations of cell in the NCS, one of which corresponded
      in size to the serotonergic cells in this nucleus and the other to a smaller
      sized cell. Comparisons of the changes in the cell packing density with
      behavioral testing, showed significant correlations with the overall test
      performance as well as with individual tests of memory function and of executive
      system functions. These findings suggest that neuronal loss in the NCS may play a
      significant role in mediating cognitive changes seen in normal aging.

PMID- 9255387
TI  - Quantitative analysis of tau protein-immunoreactive accumulations and beta
      amyloid protein deposits in the cerebral cortex of the mouse lemur, Microcebus
      murinus.
AB  - Recent studies have revealed the presence of tau protein-immunoreactive
      accumulations and beta amyloid protein (A beta) deposits in the cerebral cortex
      of the aged mouse lemur, Microcebus murinus. To examine the age-related evolution
      of these changes and compare their regional distribution to that reported for
      humans and nonhuman primates with Alzheimer's disease lesions, we performed a
      quantitative analysis of a large series of mouse lemurs aged from 1 to 13 years.
      The prevalence and density of tau protein-immunoreactive accumulations in the
      neocortex of this prosimian increased steadily with age. Neocortical areas were
      frequently affected even in young mouse lemurs, whereas the subiculum and
      entorhinal cortex were only involved occasionally in animals older than 8 years.
      As in anthropoid primates, diffuse A beta deposits were often observed in the
      cerebral cortex and amygdala of old mouse lemurs. Although all animals with
      diffuse A beta deposits had tau protein-immunoreactive accumulations in the
      neocortex, no correlation was found between the densities of these lesions in
      each area and among the areas studied. The age-dependent progression of tau
      protein-immunoreactive accumulations indicates that this prosimian may represent
      a valuable model for the study of the biochemical mechanisms of brain aging,
      while the relative sparing of hippocampus in mouse lemurs contrasts sharply with
      previous reports on neurofibrillary tangle formation in humans, and suggests that
      this animal may also be useful to investigate the biological characteristics of
      neuroprotection in this area. Furthermore, the present data indicate that A beta
      deposition in mouse lemurs is not age dependent, but occurs in a few vulnerable
      old animals.

PMID- 9255385
TI  - Neuronal integrity and astrocytic reaction in cold injury: an immunohistochemical
      investigation.
AB  - The relationship between extravasation of serum albumin and damage to the
      neuronal elements as well as the astrocytic reaction was investigated following
      cold injury, using immunohistochemistry for albumin, microtubule-associated
      protein I and II (MAPs) and glial fibrillary acidic protein (GFAP). After 30 min,
      spreading of albumin to the neuropil and uptake into nerve cell bodies and
      dendrites were clearly observed in the area surrounding the cold lesion.
      Extravasation of albumin was maximal at 24 h and extended to the ipsilateral
      hippocampus and thalamus as well as to the paramedian part of the contralateral
      cerebral hemisphere. Uptake of albumin was seen in neurons with and without loss
      or reduction of the reaction for MAPs, but the former was confined to the area
      surrounding the cold lesion. When extravasated albumin receded from the neuropil,
      the positive reaction for albumin also disappeared from the neuronal elements and
      those neurons recovered immunoreactivity for MAPs. Astrocytes immunopositive for
      albumin were observed at 24 h in the white matter, and reactive astrocytes became
      notable even in the gray matter surrounding the cold lesion. Although reactive
      astrocytes persisted even after resolution of cerebral edema, immunopositivity
      for albumin disappeared from astrocytes soon after the disappearance of the
      reaction from the neuropil. As to the mechanism, rapid endo- and exocytosis may
      take place in response to the amount of edema fluid in the surrounding
      extracellular space, where albumin may be eliminated through the transvascular
      route and/or via the cerebrospinal fluid space.

PMID- 9255388
TI  - Cerebral glucose transporter expression in HIV infection.
AB  - Abnormalities in cerebral glucose metabolism have been demonstrated in patients
      with AIDS dementia complex (ADC), with increased consumption in early disease and
      decreased utilization in late stages. The basis of these changes is unknown.
      Accordingly, a pilot study was undertaken to determine whether levels of cerebral
      glucose transporters GLUT1 and GLUT3 were altered by HIV disease. Frontal gray
      and white matter membrane preparations from patients with HIV encephalitis
      (HIVE), HIV infection without parenchymal neuropathology, and non-infected
      controls were utilized in quantitative immunoblots to measure GLUT1 and GLUT3.
      Results were expressed as a ratio of glucose transporter to structural protein
      actin. Within-group patient variability was great, precluding statistically
      significant differences between groups for any one brain region. However, when
      data for gray and white matter was pooled, results obtained statistical
      significance, with levels of GLUT1 increasing in HIV infection without
      neuropathology, and declining with HIVE. Increased GLUT1 in HIV infection without
      parenchymal neuropathology may be important in the biology of increased glucose
      consumption described with early ADC. With progression to HIVE, reduced levels of
      glucose transporters may contribute to late stage hypometabolism.

PMID- 9255389
TI  - Regressive changes of astroglia in white matter lesions in cerebrovascular
      disease and Alzheimer's disease patients.
AB  - The pathogenesis of white matter lesions, which are frequently found in ischemic
      cerebrovascular disease and Alzheimer's disease, remains unclear. Using light and
      electron microscopic immunohistochemistry for glial fibrillary acidic protein
      (GFAP) as a marker, the present study focused on the role of astroglia which show
      characteristic morphological alterations. Of 29 brains of patients with
      cerebrovascular disease and Alzheimer's disease, 4 brains showed extensive
      swelling and vacuolation of white matter astroglia with their processes
      disintegrated and beaded (termed clasmatodendrosis). No such cells were observed
      in 6 control patients. Clasmatodendritic astroglia were not intensely
      eosinophilic using hematoxylin and eosin staining and included large lipophilic
      granules in their perikarya. These astroglia were immunoreactive for serum
      proteins such as immunoglobulins, fibrinogen and complement C3, C1q and C3d, as
      well as for proteins which are known to increase in reactive astroglia, such as
      vimentin, alpha-B crystallin, apolipoprotein-E and laminin. Double labeling for
      GFAP and microglial cell markers indicated that these cells were of astroglial
      lineage. Immunoelectron microscopy for GFAP revealed that clasmatodendritic
      astroglia had condensed chromatin, lysosomes and large membrane-bound osmiophilic
      cytoplasmic inclusions, which corresponded to the lipophilic granules observed
      with light microscopy. These cytochemical features collectively suggest that
      clasmatodendritic astroglia incorporate edema fluid and phagocytose cellular
      debris, and eventually degenerate as a result of cerebral edema.

PMID- 9255390
TI  - p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with
      Parkinson's disease.
AB  - We examined the immunohistochemical localization of p35nck5a, the regulatory
      subunit of cyclin-dependent kinase 5 (cdk5), in brains obtained postmortem from
      patients with Parkinson's disease (PD) and controls. We found p35nck5a
      immunoreactivity in Lewy bodies (LB) in the substantia nigra, locus ceruleus, and
      neocortex of brains from patients with PD. In addition, p35nck5a was colocalized
      with cdk5 immunoreactivity in LB. Cdk5 is the kinase most likely to be
      responsible for the phosphorylation of neurofilament proteins of LB, which is a
      crucial step for the formation of the insoluble LB fibrils. Since p35nck5a
      regulates the catalytic activity of cdk5 by forming a heterodimer with cdk5, the
      present results strongly support the hypothesis that a cdk5-p35nck5a complex is
      involved in the formation of LB fibrils.

PMID- 9255391
TI  - Effect of transient focal ischemia on blood-brain barrier permeability in the
      rat: correlation to cell injury.
AB  - Prolonged ischemia is known to damage the blood-brain barrier, causing an
      increase in vascular permeability to proteins. We studied the time course of
      extravasation of endogenous albumin in rats after 1 and 2 h of middle cerebral
      artery (MCA) occlusion followed by 6, 12, and 24 h of recirculation. In a
      separate group of rats that had undergone 1 h of MCA occlusion and 6 h of
      recirculation, influx of [14C]aminoisobutyric acid (AIB) from blood to brain was
      also measured. After 1 h of occlusion followed by 6 h of recirculation, neuronal
      damage was evident in caudoputamen, but there were no signs of blood-brain
      barrier leakage to either AIB or albumin. At 12 h, the caudoputamen contained
      extravasated albumin, and at 24 h extravasation was extended to the somatosensory
      cortex. Animals subjected to 2 h of MCA occlusion showed albumin extravasation in
      caudoputamen already at 6 h of recirculation, and at 12 and 24 h albumin was
      abundant in the major part of the right hemisphere. This study suggests that
      damage to neurons precedes leakage of the blood-brain barrier. Even a relatively
      short period of ischemia such as 1 h will result in markedly increased vascular
      permeability. However, a longer transient ischemic insult disrupts the blood
      brain barrier earlier than a shorter one.

PMID- 9255392
TI  - GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline
      Niemann-Pick disease type C.
AB  - Feline Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal
      storage disease which shares many of the clinical, biochemical and pathological
      features of the corresponding human disorder. Cytopathological alterations in
      distinct neuronal cell populations were investigated in this animal model to gain
      a better understanding of the pathogenesis of brain dysfunction. Golgi and
      immunocytochemical methods were employed to characterize the cell architectural
      changes occurring in neuronal somata, dendrites and axons at different stages of
      disease progression. Cortical pyramidal neurons in laminae II, III, and V
      exhibited various degrees of meganeurite and/or swollen axon hillock formation
      with or without ectopic dendritogenesis. Enlarged axon hillock regions with
      neuritic processes and spines were recognized early in the progression of feline
      NPC but were less prevalent in mid to late stages of the disease. Glutamic acid
      decarboxylase (GAD) immunocytochemistry demonstrated immunoreactive spheroids in
      numerous GABAergic axons in neocortex, subcortical areas, and cerebellum.
      Parvalbumin-immunoreactive axonal spheroid distribution in brain closely mirrored
      results from the GAD studies, whereas calbindin D-28k-immunoreactive spheroids
      were conspicuously absent in most cortical and subcortical areas examined.
      Purkinje cell axonal spheroid formation progressed in a distal to proximal
      direction, with eventual involvement of recurrent axon collaterals. Purkinje cell
      death and a concomitant decrease in the numbers of spheroids in the cerebellum
      were observed late in the disease course. Clinical neurological signs in feline
      NPC occur in parallel with neuronal structural alterations and suggest that
      GABAergic neuroaxonal dystrophy is a contributor to brain dysfunction in this
      disease.

PMID- 9255393
TI  - Localization of laminin subunits in the central nervous system in Fukuyama
      congenital muscular dystrophy: an immunohistochemical investigation.
AB  - We have undertaken an immunohistochemical study of laminin subunits in the
      central nervous system (CNS) of fetuses and patients with Fukuyama congenital
      muscular dystrophy (FCMD) and of controls including five fetuses. Immunoreaction
      product deposits with antibodies to laminin alpha 1, alpha 2, beta 1 and gamma 1,
      and beta-dystroglycan were detected on the surface and vessels of the CNS of
      controls. No staining with anti-alpha-sarcoglycan antibody was detected in the
      CNS. Neurons and glia did not react with any of the antibodies used. In utero
      expression of laminin subunits and beta-dystroglycan seemed to be lower in the
      cerebrum than in the spinal cord. Moreover, immunostaining for laminin alpha 2
      and beta 1 tended to be weak on the fetal spinal cord surface. Expression of
      laminin subunits and dystrophin-associated proteins in the CNS may be modulated
      during development, as in the skeletal muscle. The distribution of immunoreaction
      product deposits was basically the same in FCMD and controls, although laminin
      alpha 2 and beta-dystroglycan expression appeared to be decreased in the CNS of
      the FCMD cases. Defects of the pial-glial barrier of the fetal brain surface have
      been considered the main cause of micropolygyria in FCMD, and these observations
      suggest that the co-localization and secondary loss of these proteins in
      association with the unknown product(s) of the FCMD gene might be involved in the
      CNS lesions of this disorder.

PMID- 9255394
TI  - Tuberous sclerosis in a 20-week gestation fetus: immunohistochemical study.
AB  - We report an autopsy case of tuberous sclerosis complex (TSC) in a 20-week
      gestational age female fetus. The brain showed lesions suggestive of early
      cortical tubers and subependymal hamartomatous nodules. The large cells within
      these nodular clusters were variably immunoreactive for glial fibrillary acidic
      protein (GFAP) and vimentin and negative for synaptophysin and neurofilament.
      Subependymal radial glia expressed both vimentin and GFAP, but subpial radial
      glia either did not express these markers (in contrast to an age-matched control)
      or were absent. Tuberin expression was noted in heterotopic neurons in the white
      matter and brain cells consistent with Cajal Retzius cells in the neocortical
      molecular layer, very weakly in superficial cortical neurons, neurons in the
      basal ganglia, Purkinje cells and external granular cells of cerebellum, cranial
      nerve nuclei neurons, occasional germinal matrix cells, ependymal cells, choroid
      plexus epithelium, and pituitary gland neuroendocrine cells; it was not seen
      within the cells of subependymal nodules. The pattern of tuberin immunoreactivity
      was similar to that which we have observed in older TSC patients. Proliferating
      cell labeling indexes were comparable in the germinal matrix of the TSC patient
      and an age-matched control. Abnormal subpial radial glia may be responsible for
      some of the neuronal migration abnormalities that appear to result in neocortical
      tubers.

PMID- 9255395
TI  - Pseudopapillary neurocytoma of temporal lobe with glial differentiation.
AB  - We present a case of cerebral neurocytoma with unusual pseudopapillary pattern,
      which was a predominant feature in the tumor and was characterized histologically
      by hyalinized vascular cores surrounded by a single or multilayered small round
      cells. Vascular hyalinization was also evident in the linear arborizing capillary
      networks in the cellular mass of the tumor. Immunohistochemically, the tumor
      cells were strongly positive for synaptophysin and neuron-specific enolase except
      some cells lining the pseudopapillae, which showed immunoreactivity for glial
      fibrillary acidic protein, vimentin and S-100 protein. Ultrastructural
      examination revealed neuritic process of the tumor cells with occasional synaptic
      structures and neurosecretory granules. This report suggests that neurocytoma
      should be included in the differential diagnosis of papillary tumors in the
      central nervous system.

PMID- 9255396
TI  - The distribution of Lewy bodies in pure autonomic failure: autopsy findings and
      review of the literature.
AB  - Pure autonomic failure (PAF; also known as idiopathic orthostatic hypotension or
      Bradbury-Eggleston syndrome) is an uncommon sporadic disorder, characterized by
      autonomic failure without other neurological deficits and histopathologically by
      cell loss in intermediolateral columns and sympathetic ganglia. Few postmortem
      studies of patients with PAF have been reported in the literature, and none have
      demonstrated Lewy bodies in distal axons, although this has been described as a
      feature in Parkinson's disease with autonomic failure. We report a patient with
      PAF who had orthostatic hypotension and urinary symptoms for 15 years prior to
      death at the age of 63 years. Postmortem findings included typical and atypical
      Lewy bodies in the substantia nigra, locus ceruleus, substantia innominata, and
      sympathetic ganglia, as well as in autonomic axons in the epicardial fat,
      autonomic nerve fascicles in periadrenal adipose tissue, and autonomic nerves in
      the muscularis of the urinary bladder. Sites of autonomic nerve involvement
      correlated with clinical symptomatology, and thus were a valuable observation in
      the complete autopsy. Systemic autopsy results should be reviewed carefully in
      patients with PAF, as Lewy bodies in this disease may be seen in distal axons at
      a great length from their primary cell bodies.

PMID- 9255397
TI  - Three-dimensional joint moments analysis in a vertical quadrupedal posture
      associated with a leg release.
AB  - This study reports on rock climbers biomechanical adjustments following a leg
      release from a quadrupedal vertical initial stance. Six climbers of international
      level have been studied. They were asked to maintain a quadrupedal posture on
      artificial holds equipped with strain gauges and then to release their right
      foot. The results show that all the rock climbers adjust differently the vertical
      forces and the horizontal forces on the holds. They distribute the vertical
      forces over the three remaining holds and the horizontal forces over the
      controlateral holds. A quasi-static three-dimensional multi-segment model was
      used to produce the net reaction forces and joint moments at each joint. Moment
      results enhance the role of the controlateral limbs, particularly the left leg.
      The gravity seems to be counteracted at the left knee joint, while body balance
      seems to be managed at the left hip and ankle joints.

PMID- 9255398
TI  - Effect of age on the exocrine pancreatic secretion of the preruminant milk-fed
      goat.
AB  - The effect of age on the exocrine pancreatic function was studied in fifteen
      Granadina goat kids during the second, third and fourth postnatal week. The
      animals, chronically catheterized, were bottle-fed on goat milk twice a day. Pure
      pancreatic juice was collected from 1 hour before and throughout 8 hours after
      milk ingestion. Pancreatic flow rate, bicarbonate and chloride concentrations,
      total protein content and enzyme activities were determined. In resting
      conditions, pancreatic flow rate augmented with age, probably reflecting an
      increase in body and pancreas weight. Resting amylase and lipase activities
      recorded significant increases during the fourth week of life. That may be
      associated, respectively, to the immediate change to a high-starch diet and to a
      simultaneous decrease in the salivary lipase levels. Our results also showed age
      related differences after ingestion of milk, mainly concerning the volume
      response and the lipase output. The latter can be explained in the same way as
      regarding resting conditions. With respect to the volume response, several
      factors could be implicated, such as the circulating levels of gastrointestinal
      hormones, the sensitivity of the pancreas to such stimuli, the maturation degree
      in the secretory mechanisms of the gland or the development of the digestive
      tract.

PMID- 9255400
TI  - Isolation of cells from ovine fetal long bone and characterization of their
      osteoblastic activities during in vitro mineralization.
AB  - Studies about bone formation and regulation are complex due to a close
      relationship between bone cells. Primary cell cultures allow to understand
      osteoblastic function. We isolated cells from the cortical metacarpal bone of 85
      or 120 day-old ovine fetuses by an enzymatic method. After first passage and cell
      amplification, the growth medium (DMEM, ascorbic acid and fetal calf serum 10%)
      was replaced at confluence by a mineralization medium (MM: DMEM, ascorbic acid,
      beta-glycerophosphate, insulin). Alkaline phosphatase (ALP) activity in cell
      matrix layer increased after 4 days of cultures in MM and maximized at day 6. We
      also measured osteocalcin, ALP and IGF-I secretion simultaneously during
      mineralization. PTH, PTHrP and 1.25(OH)2D3 decreased ALP activity in cell-matrix
      layer after 4 days of treatment in MM without fetal calf serum (FCS). Cells from
      120 day-old fetuses were cultivated in MM with 10% FCS during 32 days to induce
      mineralization. Inorganic phosphorus concentration increased in medium between
      days 5 and 12, Ca concentration decreased in medium after 12 days of culture.
      Mineralization started at day 12, in the same time ALP activity appeared in
      medium. Osteocalcin secretion increased between days 6 and 12, decreased at day
      14 and increased from day 16 until day 32. Ovine fetal bone cells produced IGF-I
      until first days of culture in MM. Such ovine osteoblast phenotype cells having
      the capacity to differentiate and mineralize in vitro would be a model to study
      the endocrine regulation of osteoblastic function in large mammals.

PMID- 9255399
TI  - Platelet-derived growth factor mediates angiotensin II-induced DNA synthesis in
      vascular smooth muscle cells.
AB  - In order to elucidate the mechanism of angiotensin II (ANG II)-induced
      proliferation in vascular smooth muscle cells in culture, growth rates and 3H
      thymidine incorporation into DNA in response to ANG II treatment were examined in
      cultured rat aortic smooth muscle cells. ANG II-treated and control cells were
      exposed to the ANG II receptor antagonists [Sar1, Val5, Ala8]-ANG II (Sar) and
      DUP753 and to antibody against platelet-derived growth factor (PDGF). In growing
      cells, ANG II acted as a moderate mitogen, inducing an increase in growth rate
      during the first two days of treatment. ANG II induced a marked increase in 3H
      thymidine incorporation in cultured vascular smooth muscle cells. The effect was
      blocked by the ANG II inhibitors Sar and DUP753 and by the PDGF antibody. ANG II
      was able to stimulate vascular smooth muscle growth in cell culture. The effect
      seemed to be mediated, at least in part, by PDGF. These results are in agreement
      with a possible role of ANG II in promoting vascular growth in physiological
      and/or pathological situations.

PMID- 9255401
TI  - Identification and initial characterization of serum growth hormone binding
      protein in the turtle Chrysemys dorbigni.
AB  - Proteins that bind growth hormone (GHBP) have been identified in the blood of
      many mammalian and avian species, but not in reptilian species. We carried out
      binding studies with the serum of turtles using chromatographic techniques as
      well as the dextran-charcoal separation method. As in other species, we found at
      least two different GHBPs: one with high MW and low affinity and the other with
      lower MW and higher affinity. The high affinity GHBP was partially purified using
      gel filtration and affinity chromatography, reaching a degree of purification of
      11,000 times (0.17 nmol/g of serum protein in the serum vs 1900 nmol/g protein in
      the purified material). When the high affinity GHBP was characterized, it was
      found to have a dissociation constant (Kd: 2.6 +/- 0.7 nM) similar to those
      described for mouse or rat, but lower than those for chicken, rabbit or man. The
      binding capacity (Bmax) was 120 +/- 43 fmoles/mg of protein, which can be also
      expressed as 1.08 +/- 0.38 pmol/ml of serum. A preliminary MW estimation of 50-60
      kDa was obtained for turtle higher affinity GHBP. The specificity of this high
      affinity GHBP is somatogenic, since bovine GH competes as well as human GH for
      125I-hGH bound to binding protein, while ovine PRL competes only partially and
      with low affinity. Unrelated hormones, as insulin and glucagon, can not displace
      the 125I-hGH bound to turtle GHBP. A very important seasonal variation in turtle
      GHBP activity was observed: maximum binding was found in November (springtime),
      followed by a continuous decline over March and May.

PMID- 9255402
TI  - Modifications of antioxidant capacity and heart electrical activity induced by
      hydroperoxide in normal and vitamin E-fed rats.
AB  - Wistar rats, fed control or vitamin E-supplemented diet, were subjected to
      oxidative stress by a ten day treatment with daily intraperitoneal dose of tert
      butyl hydroperoxide (TBHP) (0.1 mumol/100 g body weight). The effectiveness of
      both diet and hydroperoxide treatment was established by determining the
      antioxidant capacity of blood, liver, and heart with an enhanced luminescence
      method. While the diet addition of vitamin E increased the antioxidant capacity
      of all the tissues in treated and untreated animals, the hydroperoxide treatment
      failed to decrease liver antioxidant capacity in control diet fed animals. The
      effect of the reiterated production of free radicals on electrophysiological
      properties of myocardium was determined by studying the heart rate in vivo and
      the time course of the surface electrical activity in papillary muscle fibers in
      vitro. In vivo, a significant tachycardia was found only in TBHP-treated, normal
      diet fed rats. The duration of action potential, recorded in Krebs' solution at
      26 degrees C, was not affected by diet in untreated animals but was modified by
      hydroperoxide treatment in a diet-dependent way: shortened in normal diet-fed
      rats and lengthened in vitamin E-supplemented diet-fed rats. On the basis of
      analogies with the results of electrophysiological recordings on different
      preparations subjected to oxidative stress in vitro, we suggest that the changes
      of action potential duration might depend on relative levels of added pro-oxidant
      and cell antioxidants.

PMID- 9255404
TI  - Exocrine pancreatic secretion in suckling goats. Adaptative effects of maternal
      milk and a milk substitute.
AB  - Suckling goats were fed ad libitum during the first month of their life by goat
      milk or by a milk replacer. These diets differed in the amount of fat and the
      type of protein. The composition of the exocrine pancreatic secretion in the
      basal period and in response to food were compared in both conditions. Pancreatic
      juice was collected one hour before meal intake up to the 8th postprandial hour.
      Pancreatic flow rate, bicarbonate and chloride levels, total protein and enzyme
      activities were measured. In resting conditions and in response to food, the
      lipase activity was found to be significantly lower in the group fed with milk
      replacer, which was poorer in fat. These results indicate an adaptation of the
      enzyme output to the available quantity of its substrate, similar to that
      described in the rat. Postprandial differences in the pancreatic flow rate,
      electrolytes and total protein were found between both groups. Their origin can
      be attributed to the protein used (soyabean) in the milk substitute. Such soya
      protein alters the normal clot formation in the abomasum and allows an
      accelerated abomasal digesta outflow and duodenal pH alkalinisation.

PMID- 9255403
TI  - Induction of transcription from the long terminal repeat of the intracysternal
      particles type A (IAP) by X-irradiation.
AB  - Intracisternal A particles (IAPs) are retrovirus-like entities that are present
      in many embryonic and transformed cells of Mus musculus. They present long
      terminal repeats (LTRs) which control the promotion and regulation of their
      transcription. Using a construction expressing a reporter gene under the control
      of the entire long terminal repeat (LTR) of IAP in transfected murine fibroblast
      BALB/c 3T3 cells clone D152, we were able to show that the IAP-LTR is activated
      by X-irradiation in a time-dependent manner. The relative CAT activity increased
      with increasing X-irradiation doses, reaching a maximum at 75-150 cGy, followed
      by a drop in activation. In addition, X-induced D152 mouse cells produced
      extracellular factor(s), in response to X-irradiation, which activated the IAP
      LTR in non-irradiated cells. This factor(s) was detected both when transfected
      cells were cocultured with inducing cells and when conditioned medium from
      irradiated cultures was added to the cell cultures. The use of suramin, a strong
      polyanonic molecule which has been reported to trap growth factors, induces a
      high reduction of the indirect activation.

PMID- 9255405
TI  - Beta-adrenergic-induced calcium efflux in rat parotid gland. Is mitochondrial
      Na+/Ca2+ exchange involved?
AB  - The effects of diltiazem were examined on 45Ca efflux in rat parotid glands.
      First, we showed that mitochondrial Na+/Ca2+ exchange occurs in rat parotid
      glands and that diltiazem inhibited the mitochondrial Na(+)-dependent calcium
      efflux. We also confirmed that in rat parotid gland, diltiazem did not modify
      calcium movements at plasma membrane level. Secondly, we tested the effects of
      diltiazem on pieces of parotid glands. Diltiazem alone induced 45Ca efflux from
      parotid lobules. When the effect of diltiazem was tested on isoproterenol-induced
      45Ca efflux, the effects of the two drugs were less than additive. By comparison,
      diltiazem did not modify carbachol induced 45Ca efflux. Diltiazem was able to
      induce calcium efflux from an intracellular calcium pool, which is not the IP3
      sensitive one. These data support the previous hypothesis that isoproterenol and
      carbachol do not mobilize the same calcium pool. Although we did not precisely
      determine the calcium pool sensitive to beta-adrenergic stimulation, we cannot
      rule out the hypothesis that mitochondria would be that store.

PMID- 9255406
TI  - Gender differences in blood ammonia response during exercise.
AB  - In order to test for possible gender differences in blood ammonia accumulation
      during exercise, groups of young, physically active women (n = 8) and men (n = 8)
      performed an incremental load (until exhaustion) and a constant load (30 min at
      75% VO2 peak) treadmill exercise test. The groups were matched for physical
      activity habits. VO2 peak was significantly higher in males (55.8 +/- 2.6
      ml/kg/min) than in females (44.5 +/- 2.8 ml/kg/min). During the incremental
      exercise test to exhaustion blood ammonia concentration progressively increased
      with increasing workload in both groups. Blood ammonia concentration was
      significantly higher in males at 70, 80 and 90% of VO2 peak. Peak blood ammonia
      concentration was higher in males than in females (155 +/- 35 vs 136 +/- 67
      mumol/l, respectively), but the difference did not reach the level of statistical
      significance. During the constant load exercise test blood ammonia concentration
      increased in both groups. At the end of the exercise test blood ammonia
      concentration was significantly higher in males than in females (137 +/- 42 vs 91
      +/- 24 mumol/l, respectively). In conclusion, the blood ammonia concentration
      during submaximal exercise is dependent on gender, the males showing higher
      ammonia concentrations compared to females at the same relative workload (percent
      of VO2 peak).

PMID- 9255407
TI  - Postnatal development of the exocrine pancreas in suckling goat kids.
AB  - A total of 25 preruminant Granadina breed goats were used. They were bottle-fed
      goat milk ad libitum from postnatal day 3 to 28. Until the age of 3 d, kids were
      fed colostrum. Body weight, pancreas weight, total protein concentration, enzyme
      activities in pancreatic tissue and hormone concentrations (cortisol, gastrin, T3
      and T4) were determined at 3, 7, 14, 21 and 28 d of age. Our results show that
      the rates of pancreatic synthesis and secretion of chymotrypsin are well
      developed at birth in the kid, and may compensate for possible deficiencies in
      gastric and/or enterocytes intracellular proteolysis. In week 4, there was a
      marked increase in amylase activity, change that can be attributed to the
      beginning of the transitional period known as weaning. The significant increase
      in circulating concentration of cortisol during week 4 suggests the involvement
      of corticosteroid as a mediator of pancreatic development at weaning. Changes in
      blood levels of this hormone are believed to be important in the expression of
      amylase in the neonatal period. However, T3-T4 blood levels remained unchanged
      from d 3 to 28, suggesting that, in the kid, these hormones appear to have no
      clear influence upon the postnatal development of the exocrine pancreas.

PMID- 9255408
TI  - Structural diversity of dermatan sulphate in porcine dermis.
AB  - The structural diversity of dermatan sulphate (DS), the major glycosaminoglycan
      component of mammalian skin, was investigated by examining different layers of
      porcine dermal tissue using 1H-NMR and disaccharide compositional analysis by
      HPLC. Structural reporter signals were assigned using one-dimensional (1D) 1H-NMR
      differential transient NOE and 1D totally correlated spectroscopy (TOCSY)
      spectra, measured at different probe temperatures. The results of these studies
      on 12 sliced layers (average thickness of 250 microns) of skin show that the
      content of glucuronic acid in DS decreases when moving from the outer surface of
      the skin to the inside, while the degree of sulfation of the C-2 hydroxy group of
      iduronate and the C-4 and C-6 hydroxy groups of N-acetylgalactosamine increases
      with depth. These results suggest that the utility of analysis of DS from various
      depths in porcine skin clearly show the origin of each sample, and might be
      useful for the quality control of these biological materials in clinical use.

PMID- 9255409
TI  - Internalization of non-permeant materials into cultured mammalian cells by vortex
      stirring in the presence of a high molecular weight polyacrylic acid: direct
      evidence of internalization and its dependence on the cell lines.
AB  - Laser scanning confocal fluorescence microscopic analysis provided a direct
      evidence of the internalization of non-permeant Lucifer Yellow and a dextran of
      MW 4400 into leukemia L1210 cells when the cells were vortex-stirred in the
      presence of a high molecular weight polyacrylic acid, A-119 (MW ca. 9 x 10(6)).
      The morphology of A-119-treated cells was probed by scanning electron microscopic
      analysis using 2% glutaraldehyde for fixation. The cells immediately after vortex
      stirring with A-119 showed many blebs on the cell surface, indicative of local
      weakening of the plasma membrane. The blebby surface returned to normal within 5
      min at 37 degrees C, but not completely at 0 degree C even after 20 min. Several
      cultured cell lines, murine splenocytes, and Ehrlich ascites carcinoma cells were
      particularly susceptible to permeabilization by this method, although the
      efficiency varied from one type of cell to another.

PMID- 9255410
TI  - Metabolic fate of ulinastatin (2); Pharmacokinetics in rabbits following intra
      articular administration.
AB  - The absorption and distribution of ulinastatin following intra-articular
      administration of [125I]ulinastatin to rabbits were determined and kinetic
      analysis using a multi-compartment model was performed. At 4 h after
      administration, the content of radioactivity in the synovial fluid, which was
      comparable to that of the immunoreactive ulinastatin, was 14.51% of the dose and
      decreased in a biphasic manner. The highest level of radioactivity was observed
      in the synovial membrane, followed by the meniscus, ligament, cartilage and
      patella, the radioactivities of which also declined biphasically. After intra
      articular administration, the plasma concentration of total radioactivity
      increased slowly and reached maximum at 4.3 h, and then declined slowly in a
      monophasic manner with a half-life of 10.8 h. The radioactivity of the high
      molecular weight fraction in plasma, which reached maximum at 1.7 h after
      administration and then declined with a half-life of 11.8 h, was consistent with
      the time curve for immunoreactive ulinastatin in the plasma through 24 h after
      the administration. Within 8 and 24 h after administration, respectively, 1.48
      and 4.66% of the administered radioactivity were transferred to the lymphatic
      fluid. The pharmacokinetics of [125I]ulinastatin after an intra-articular
      administration could be explained using a multi-compartment model in which a
      portion of the administered ulinastatin was absorbed via the lymphatic system.
      This finding suggested that ulinastatin was rapidly distributed and retained for
      a long period of time in the joint tissues. In addition, the pharmacokinetics of
      ulinastatin following intra-articular administration indicated typical flip-flop
      kinetics.

PMID- 9255411
TI  - Antiemetic effects of morphine on motion- and drug-induced emesis in Suncus
      murinus.
AB  - Emetic and antiemetic effects of morphine were investigated in Suncus murinus.
      Subcutaneous (up to 30 mg/kg) or intracerebroventricular administration (50
      micrograms) of morphine failed to cause emesis. However, pretreatment with
      morphine (s.c.) prevented the emesis induced by nicotine (10 mg/kg, i.p.), copper
      sulfate (40 mg/kg, p.o.), cisplatin (20 mg/kg, i.p.) and motion stimulus. These
      results suggest that morphine has only antiemetic potency and may block a common
      mechanism for the emetic reflex of suncus, because the antiemetic effects of the
      drug were exerted irrespective of the stimulus.

PMID- 9255412
TI  - A possible thermodynamic approach to the change of rectal temperature of rabbits
      due to forced restricting conditions.
AB  - It was found that the rectal temperature of rabbits restricted by a normal neck
      stock position dropped about 1.2-1.5 degrees C when the restriction position
      changed from a normal restriction to a supine restriction position. This
      temperature change was also reversible. We studied the mechanisms of this
      phenomenon from a thermodynamic point of view and obtained the following results:
      1) The rectal temperature of rabbit restricted in the supine position did not
      increase after the injection of lipopolysaccharide (LPS). 2) In the supine
      restricted rabbit, endogenous pyrogen which was induced by the injection of LPS
      to these rabbits appeared the same as the control. 3) Some pharmaceuticals
      (urethan, iproniazid, atropin and hexamethonium) did not show any influence on
      the drop of rectal temperature in either normal or supine restrictions. 4) The
      rectal temperature of shorn rabbits dropped more than that of normal rabbits in
      both normal and supine restrictions. 5) When the normal restriction position was
      changed to the supine and prone restriction positions, the mean surface
      temperature was also decreased. From these results, it was concluded that rabbit
      rectal temperature was changed with a change in the restriction position which
      could change the surface skin area.

PMID- 9255413
TI  - Involvement of a novel mouse hepatic microsomal esterase, ES46.5K, in the
      hydrolysis of phthalate esters.
AB  - ES46.5K, a novel esterase from mouse hepatic microsomes (Watanabe K., et al.,
      Biochem. Mol. Biol. Int., 31, 25-30 (1993)), catalyzed hydrolysis of phthalate
      esters. ES46.5K and mouse hepatic microsomes hydrolyzed diethyl-, dibutyl-,
      diisobutyl-, dioctyl- and diethylhexyl phthalates, whereas dicyclohexyl- and
      diphenyl phthalates having ring structure were not hydrolyzed by the enzymes.
      Vmax (mumol/min/mg protein)/K(m) (microM) ratios of ES46.5K for diethyl-, dibutyl
      , diisobutyl-, dioctyl- and diethylhexyl phthalates were 291, 2786, 565, 51 and
      57, respectively, while those of microsomes were 0.58, 0.83, 1.71, 0.05 and 1.10,
      respectively. The hydrolytic activity of ES46.5K was inhibited by
      diisopropylfluorophosphate and bis-p-nitrophenylphosphate. These results suggest
      that ES46.5K has high catalytic activity for phthalate esters and some role in
      the metabolism of phthalate esters in mice.

PMID- 9255414
TI  - CP2289, a new 5-HT3 receptor ligand: agonistic activities on gastroenteric
      motility.
AB  - A new 5-HT3 receptor ligand, CP2289, was synthesized and pharmacologically
      tested. Although CP2289 inhibited the Bezold-Jarisch reflex, it contracted the
      excised ileal muscle of mice, rats and guinea pigs. This response may reflect a
      partial agonist character of CP2289 in the gut. In vivo antiemetic and gastric
      emptying tests gave similar results.

PMID- 9255415
TI  - Effect of benzene extract of Hibiscus rosa sinensis on the estrous cycle and
      ovarian activity in albino mice.
AB  - The benzene extract of Hibiscus rosa sinensis flowers was administered
      intraperitoneally at the dose levels of 125 and 250 mg/kg body weight to adult
      mice and resulted in an irregular estrous cycle with prolonged estrus and
      metestrus. An increase in the atretic follicles and the absence of corpora lutea
      indicate the antiovulatory effect of the extract. The extract also showed
      estrogenic activity in immature mice by early opening of the vagina, premature
      cornification of the vaginal epithelium and an increase in uterine weight.
      Therefore the antiovulatory effect may be due to an imbalance in the hormonal
      environment, as there may be an increase in the endogenous secretion of estrogen
      by atretic follicles, and also to the estrogenicity of the flower extract.

PMID- 9255416
TI  - Wide range of molecular weight distribution of mitogenic substance(s) in the hot
      water extract of a Chinese herbal medicine, Bupleurum chinense.
AB  - In this study, we examined the contribution of lignin-like materials in lower
      molecular weight (MW) fractions from the hot water extract of Bupleuri Radix
      (Bupleurum chinense) (HWE-BR) for their immunopharmacological activities.
      Mitogenic activity was detected in all the fractions of MW ranges: lower than 1.0
      kDa, 1.0-3.5 kDa, 3.5-10 kDa, and 10-50 kDa. After NaClO2 treatment of these
      subfractions, UV spectra, ESR spectra, mitogenic activities on murine B-cells,
      and the activity of inducing nitric oxide in RAW 264.7 cells were significantly
      reduced, suggesting that lignin-like polyphenolic substance(s) of various MW
      might take part in these activities. The intensity of ESR spectra and mitogenic
      activities were stronger in higher MW subfractions, thus the content of stable
      radical species and/or the degrees of polymerization would be important for their
      immunopharmacological activities.

PMID- 9255417
TI  - Application of PCR-RFLP and MASA analyses on 18S ribosomal RNA gene sequence for
      the identification of three Ginseng drugs.
AB  - In order to develop convenient and reproducible methods for the identification of
      Ginseng drugs at a DNA level, PCR-Restriction fragment length polymorphism (PCR
      RFLP) and Mutant allele specific amplification (MASA) analyses were applied,
      based on differences of the 18S rRNA gene sequence among three Panax species. The
      PCR product of each species on the 18S rRNA gene was digested with the
      restriction enzymes Ban II and Dde I. Each fragment gave unique electrophoretic
      profiles for each species (PCR-RFLP analysis). The extracted DNA of each species
      was amplified by PCR using a designed species-specific oligonucleotide primer.
      The expected size of the fragments corresponding to each species were detected
      only when the optimum temperature and reaction time for annealing and extension
      were established (MASA analysis). These two analytical methods were carried out
      on three Ginseng drugs and the same results as in their original plants were
      obtained. The results suggest that PCR-RFLP and MASA analyses under the
      established conditions are convenient for identifying three Ginseng drugs.
      Moreover, to insure completion of the identification, a partial sequence of the
      plastid gene matK was determined in addition to the 18S rRNA gene. The gene
      sequences of three Panax species were of 1259 base pairs and that of P.
      quinquefolius was different from the other two at nucleotide position 102.

PMID- 9255418
TI  - Molecular cloning of pea cDNA encoding cycloartenol synthase and its functional
      expression in yeast.
AB  - The cDNA encoding cycloartenol synthase [EC 5.4.99.8] has been isolated from pea
      seedling by an efficient PCR using sets of degenerate primers based on the highly
      conserved sequences of the known 2,3-oxidosqualene cyclase cDNAs. The obtained
      cDNA contains a 2271-bp open reading frame and is encoding a predicted protein of
      757 amino acids with high homology (81%) to Arabidopsis thaliana cycloartenol
      synthase. The PCR-amplified open reading frame (ORF) has been inserted into
      pYES2, an expression vector in yeast, under the control of galactose-inducible
      promoter. Significant cycloartenol synthase activity has been found in the
      homogenate of the yeast transformed with the plasmid containing PCR-amplified
      ORF.

PMID- 9255419
TI  - Inhibitory effects of shouseiryu-to on two-stage carcinogenesis. II. Anti-tumor
      promoting activities of lignans from Asiasarum heterotropoides var. mandshuricum.
AB  - Two lignans, asarinin (6) and xanthoxylol (7), were isolated from the radix of
      Asiasarum heterotropoides var. mandshuricum, which consist of a kampo
      prescription, Shouseiryu-to, as inhibitors of Epstein-Barr virus early antigen
      (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). These
      lignans also exhibited remarkable inhibitory effects on a two-stage
      carcinogenesis test of mouse skin and pulmonary tumors. Furthermore, it was
      confirmed that these hydrophobic lignans dissolved in the water decoction of
      Shouseiryu-to, and these lignans might be among the active constituents of this
      kampo prescription in terms of its anti-tumor-promoting activity.

PMID- 9255420
TI  - Anti-hyperliposis effect of maitake fruit body (Grifola frondosa). I.
AB  - Experimental rat models (5-week-old Sprague-Dawley rats) with hyperlipemia were
      prepared by feeding high-cholesterol feed containing sodium cholate and casein as
      a protein source. Dried maitake (Grifola frondosa) powder was mixed with the
      basic high-cholesterol feed and the serum lipids were periodically measured.
      Values of cholesterol, triglyceride and phospholipid in serum of rats in the
      maitake-feed group were suppressed by 0.3-0.8 times those in animals fed the
      basic feed, the latter values being close to those in rats given normal feed. The
      value of high density lipoprotein (HDL)-cholesterol in serum which is generally
      reduced by the ingestion of high-cholesterol feed remained the level it was at
      the beginning of the experiment. Weights of extirpated liver and epididymal fat
      pads were significantly less (0.6-0.7 times) than those in the basic feed group,
      indicating that maitake inhibits lipid accumulation in the body. Liver lipids
      were also measured and the values were found to be decreased by maitake
      administration as true of serum lipid, suggesting maitake has an anti-liver lipid
      activity. Measurement of the amount of total cholesterol and bile acid in feces
      showed, the ratio of cholesterol-excretion had increased 1.8 times and bile acid
      excretion 3 fold by maitake treatment. From these results, it is believed that
      maitake helps to improve the lipid metabolism as it inhibits both liver lipid and
      serum lipid which are increased by the ingestion of high-fat feed.

PMID- 9255421
TI  - Metabolism of the intravenously administered recombinant human basic fibroblast
      growth factor, trafermin, in liver and kidney: degradation implicated in its
      selective localization to the fenestrated type microvasculatures.
AB  - The fate of trafermin (recombinant human basic fibroblast growth factor) was
      examined after intravenous administration of its iodinated form to rats.
      Autoradiography at 5 and 30 min after the injection showed that 125I-trafermin is
      localized specifically in the fenestrated endothelium through binding to heparan
      sulfate proteoglycans (HSPG) in liver, kidney, adrenal, spleen, hypophysis and
      bone marrow. Metabolites in the organs were examined at 5 min and 24 h after the
      injection. More than 73% of radioactivity in liver and kidney was extractable at
      either time point, and a large majority of the extracted radioactivity was
      heparin-binding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) revealed that the substantial radioactivity recovered from liver and kidney
      can commonly be attributed to a peptide with the same molecular weight as the
      intact trafermin (B-1, 17.7 kDa) and only three truncated metabolites (B-2, 15.0
      kDa; B-3, 7.2 kDa; B-4, 4.2 kDa). Because no truncated metabolites were found in
      serum, these metabolites seem to be produced inherently in liver and kidney.
      Although they all retained heparin-binding capacity, only B-1 and B-2 exhibited a
      stimulatory effect on proliferation of endothelial cells, and these bioactive
      peptides disappeared completely from liver within a day, indicating a rapid
      inactivation process in the organs. Taken together with the morphological
      evidence on autoradiography, it seems most likely that the injected trafermin
      could be inactivated in sinusoidal endothelial cells, probably through a well
      known internalization mechanism of the basic fibroblast growth factor-HSPG
      complex.

PMID- 9255422
TI  - The effect of membrane surface potential on the permeability of anionic compounds
      across the apical membrane in human intestinal epithelial (Caco-2) cells.
AB  - The effect of membrane surface potential of the apical side on the intracellular
      uptake of ionic compounds was investigated using the human colon adenocarcinoma
      cell line (Caco-2). The transepithelial transport of indolepropionic acid and
      tryptamine was consistent with the uptake behavior shown by rat intestinal brush
      border membrane (BBM) vesicles. Imipramine, which diminished the negative charge
      of the membrane surface (for both Caco-2 and BBM), acted to increase the uptake
      of the anionic compounds, indolepropionic acid and ceftibuten, and to decrease
      that of tryptamine (cationic compound) by both the Caco-2 monolayer and the
      intestinal BBM vesicles at a pH of 7.5. These results suggest that the effects of
      membrane surface potential on the permeability of ionic compounds were detectable
      on the Caco-2 cell line as well as the BBM vesicles. On the other hand, the
      inhibition of H(+)-linked transport and the stimulation of the surface charge
      regulated uptake of ceftibuten have occurred simultaneously on the Caco-2 cell
      line in the presence of imipramine. It seems that the membrane surface charge
      (negative) plays an important role in the transport process of ionic compounds
      across the intestinal epithelium.

PMID- 9255423
TI  - Antibacterial activity of two alkylamines integrated an indane scaffold: mimicry
      of a complementary unit on magainin 2.
AB  - Based on the antibacterial activity of 9-phenylnonylamine (pC9a) against
      Escherichia coli (ATCC29522) and Staphylococcus aureus (ATCC25923), we have
      further tested the inhibitory ability of the growth of the bacteria by (+/-)1-(4
      aminobutyl)-6-benzylindane (PM2) and (+/-)1-benzyl-6-(4-aminobutyl) indane (PM3),
      that is, two kinds of 1,6-disubstituted indanes. In an in vitro assay, they
      showed almost the same antibacterial activities against the bacteria as pC9a, as
      well as that of magainin 2 analogs (i.e., the peptides MSI-78 and 87-ISM), except
      in the case of 87-ISM against S. aureus. At the MIC (minimum inhibitory
      concentration) values, however, their killing rate of E. coli is actually quicker
      than pC9a. This indicates that an indane scaffold, used as a template to mimic a
      part of the alpha-helical structure of magainin 2, can accelerate the killing
      rate. At present, however, it is unknown whether either the hydrophobicity or the
      alpha-helical structure, or both, of the indane scaffold is involved in
      accelerating the rate. Moreover, these two indanes also showed stronger
      antibacterial activity against two strains of Helicobacter pylori (ATCC43526,
      ATCC43579) than either pC9a or magainin 2 related peptides.

PMID- 9255424
TI  - On the antibacterial activity of normal and reversed magainin 2 analogs against
      Helicobacter pylori.
AB  - Magainin 2 is an antimicrobial peptide isolated from the skin of Xenopus laevis.
      We have tested the antibacterial activities of normal and reversed magainin 2
      analogs against two strains of Helicobacter pylori (ATCC 43526, ATCC 43579),
      compared with those against Escherichia coli (ATCC 25922) and Staphylococcus
      aureus (ATCC 25923). Among these analogs, MSI-78A showed the strongest activity
      against H. pylori. The MIC (minimum inhibitory concentration) values were almost
      the same as those against E. coli and S. aureus. No or lesser activity was
      observed in all the reversed peptides compared to the corresponding normal
      magainin 2 analogs. Based on the CD (circular dichroism) measurement, the more
      active peptide tends to show a higher alpha-content. The positively-charged five
      amino acids (KILKK) positioned at the C terminus on the amphipathical alpha
      helical structure play important roles in exerting the strong activity against H.
      pylori. This indicates that the net charge of the cell surface in H. pylori may
      be more negative than that of E. coli, though both strains belong to the same
      genus.

PMID- 9255425
TI  - The effects of crude polysaccharide fractions of 4 kinds of kampo-hozai
      administered orally on nitric oxide production by murine peritoneal macrophages.
AB  - In order to characterize the pharmacological role of the crude polysaccharide
      fraction in kampo-hozai, we chose 4 kinds of kampo-hozai, Shosaiko-to, Daisaiko
      to, Hachimi-jio-gan and Hochu-ekki-to, and studied the effects of their crude
      polysaccharide fractions on nitric oxide (NO) production by 3% thioglycollate
      induced murine peritoneal macrophage. Oral administration of these fractions for
      7 d augmented lipopolysaccharide (LPS, 0.1-10 micrograms/ml)-induced NO
      production by peritoneal macrophages. These results suggest the possibility that
      a crude polysaccharide fraction affect the macrophage function in most kampo
      hozai.

PMID- 9255426
TI  - Effects of various absorption enhancers on the intestinal absorption of water
      soluble drugs by in vitro Ussing chamber method: correlation with an in situ
      absorption experiment.
AB  - The effect of absorption enhancers on the small and large intestinal absorption
      of drug in rats was examined using an in vitro modified Ussing chamber method,
      and the results were compared with those from an in situ absorption experiment.
      Phenol red was chosen as a model drug, while the absorption enhancers used were
      sodium glycocholate (Na-GC), sodium taurocholate (Na-TC), sodium deoxycholate (Na
      DC), EDTA, sodium salicylate (Na-Sal), sodium caprate (Na-Cap), diethyl maleate
      (DEM) and N-lauryl-beta-D-maltopyranoside (LM), all used at a concentration of 20
      mM. This modified Ussing chamber method showed that Na-DC, EDTA and LM were the
      most effective absorption enhancers in the large intestine. A good correlation
      exists between the area under the curve (AUC) (in situ loop model) and the
      cumulative amount of phenol red absorbed (in vitro modified Ussing chamber
      method). These results indicated that the in vitro modified Ussing chamber method
      can be used to evaluate the effects of various absorption enhancers in the
      intestine.

PMID- 9255427
TI  - Simultaneous determination of the lactone and carboxylate forms of 7-ethyl-10
      hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), in rat
      plasma by high performance liquid chromatography.
AB  - We established a high performance liquid chromatography (HPLC) method for the
      simultaneous determination of the lactone and carboxylate forms of 7-ethyl-10
      hydroxycamptothecin (SN-38), the active metabolite of the antitumor drug
      irinotecan (CPT-11), in rat plasma. Plasma samples were pretreated with chilled
      MeOH and zinc sulfate to precipitate protein, and were then directly injected
      into the HPLC system. Chromatography was carried out with a Puresil C18 column
      (particle size 5 microns), and the mobile phase consisted of 0.1 M ammonium
      acetate buffer (pH 5.5) and acetonitrile (70/30, v/v) containing 20 mM of tetra-n
      pentylammonium bromide. The column effluent was monitored with a
      spectrofluorometer (excitation wavelength 380 nm, emission wavelength 540 nm).
      The method was valid for SN-38 lactone (5-2500 ng/ml) and carboxylate (5-1000
      ng/ml).

PMID- 9255428
TI  - Molecular cloning and sequence analysis of the dnaA gene of Staphylococcus
      aureus.
AB  - The dnaA gene of Staphylococcus aureus has now been cloned and sequenced. The
      deduced amino acid sequence of Staphylococcus aureus DnaA protein is 62% and 39%
      identical to those of the DnaA protein from Bacillus subtilis and Escherichia
      coli, respectively. Expression of the dnaA gene of Staphylococcus aureus in
      Escherichia coli caused lethality in an oriC-dependent manner.

PMID- 9255430
TI  - Shifting attention between global features and small details: an event-related
      potential study.
AB  - In two experiments, large letters H or Z composed of small letters (also H or Z)
      were presented. Subjects had to make a two-choice motor response (e.g. H--left
      key, Z--right key). A cue presented 500 ms before the letter indicated which
      level (global or local) was relevant. In Experiment I, a third letter (T)
      sometimes appeared either at the cued or the non-cued level; in the former case,
      subjects had to shift their attention and to respond to stimulus features located
      at the non-cued level. The interference effect (RT delay in response to
      incongruent stimuli as compared to congruent ones) was larger when the local,
      rather than global, level was cued. A slow anterior negativity preceding globally
      cued stimuli and shorter N1 and P2 ERP component latencies to these stimuli
      indicated better preparation for processing of global, as compared to local,
      stimulus features. The shift from local to global focus yielded a larger increase
      of RT, error rate, and of the P600 latency than the global-to-local shift. The
      P600 latency changes were parallel to those of RT. In Experiment II, the
      attentional shift was provoked by stimulus color red-colored letters meant that
      the cue was invalid, and thus, subjects had to respond to the non-cued level.
      Neither the interference nor the attentional shift demonstrated any asymmetry
      between the global and local levels. ERPs also did not differ substantially after
      local and global cues. In the condition demanding a shift of focus (invalid cue,
      incongruent letter), a positive deflection of the lateralized readiness potential
      indicated the activation of the wrong response channel. The large RT increment in
      this condition was not accompanied by an increase of the P600 latency. Two
      possible mechanisms of attentional shift may be proposed, the first related to
      perceptual processes (e.g. an additional visual search), and the second, to the
      competition between two response intentions.

PMID- 9255431
TI  - P300 from a single-stimulus paradigm: auditory intensity and tone frequency
      effects.
AB  - The P300 component of the event-related brain potential (ERP) was elicited with
      auditory stimuli in two different tasks. The oddball paradigm presented both
      target and standard stimuli; the single-stimulus paradigm presented a target but
      no standard tone stimulus, with the inter-target interval the same as that for
      the oddball condition. Experiment 1 manipulated stimulus intensity and Experiment
      2 manipulated tone stimulus frequency, with the relative target probability
      maintained 0.20 for both tasks. P300 amplitude and latency were highly similar
      for the oddball and single-stimulus procedures in both experiments across
      independent variables. The findings suggest that the single-stimulus paradigm may
      prove useful in experimental and applied contexts that require very simple ERP
      task conditions.

PMID- 9255432
TI  - Uninformative symbolic cues may bias visual-spatial attention: behavioral and
      electrophysiological evidence.
AB  - Event-related brain potentials and response latencies were measured in an
      experiment where centrally presented arrow cues were followed by left or right
      visual target stimuli. In one condition, target location was indicated by the
      cues with 75% validity. In another condition, the precues were uninformative with
      respect to target location. Faster response times and larger negativities in the
      ERPs at midline electrodes were measured for targets at cued locations following
      informative cues, but also with uninformative precues. This indicates that visual
      spatial attention may be biased involuntarily by central symbolic precues.

PMID- 9255429
TI  - What's in a pause: event-related potential analysis of temporal disruptions in
      written and spoken sentences.
AB  - Two experiments examined the effects of disrupting the temporal patterns that
      develop during sentence reading and listening. Sentences were presented either
      visually, one word at a time (Experiment 1) or as natural speech (Experiment 2).
      Half of the sentences were familiar (proverbs or idioms) while the other half
      were constructed anew for these experiments. Within half the sentences, there was
      an unexpected 600-ms delay between the final two words. In both modalities, the
      amplitude of the N400 component of the event-related brain potential (ERP) to
      sentence final words was larger for unfamiliar than familiar sentences. The
      results in the two modalities differed, however, in that a Contingent Negative
      Variation (CNV) developed during the delay interval in the visual modality,
      whereas in the auditory modality the delay was marked by an emitted potential.
      The present results show that temporal patterns are processed differently in
      natural speech and in reading words presented one at a time in the center of a
      computer screen.

PMID- 9255433
TI  - The role of blood rheology in regulating blood pressure.
AB  - Review of the role of blood rheology in regulating blood pressure discloses that
      macromolecular binding to the erythrocyte membrane is a significant factor.
      Evidence is summarized supporting the thesis that blood viscosity is a prime
      regulator of blood pressure. Macromolecules may bind to erythrocytes and other
      macromolecules forming structures that increase blood viscosity when the blood
      stream flow rate is decreased. Review of the nature and extent of RBC membrane
      binding and a model for relating these bonds to blood pressure are presented.

PMID- 9255434
TI  - In vitro estimation of red blood cells' aggregation using ultrasound Doppler
      techniques.
AB  - Aggregation of red blood cells (RBCs) is one of the principal hemorheological
      factors which plays an important role in capillary circulation. In order to study
      RBC's aggregation, an ultrasound Doppler in vitro technique, using pulsed wave
      monoelement pencil 4 MHz probes, was designed. A hydraulic pump system has been
      implemented, using an electric step motor that establishes in a certain distance,
      a laminar blood flow profile into a rectangular cross-section plexiglass tube.
      Blood coming from blood collection bags was used and following certain typical
      measuring protocols, red blood cells' samples of various parameters and
      conditions were acquired. Adding dextrans to the blood samples, red blood cells
      aggregation was achieved and observed for various hematocrit values. Both the
      emitted and the backscattered signals were driven to a system containing a multi
      channel digital oscilloscope--of high sampling rate and processing capabilities-
      and a powerful PC with a high acquisition A/D card and special control software.
      The estimation of mean aggregates size--by measuring the mean ultrasonic
      intensity scattered by the blood sample--led us to a qualitative, in vitro
      ultrasonic method.

PMID- 9255435
TI  - The effect of RheothRx Injection on the hemorheological parameters in patients
      with acute myocardial infarction.
AB  - This study evaluated the hemorheological effects of a nonionic block copolymer
      surfactant, RheothRx Injection, on the hemorheological parameters in patients
      with acute myocardial infarction (AMI). For the in vitro study blood from 24
      patients admitted with chest pains (mean age: 49 +/- 11 yrs) was sampled after
      admission and in AMI cases (15 patients, mean age: 53 +/- 13 yrs) a second sample
      was collected 48 hours later. Different concentrations of RheothRx were added
      (0.25, 0.5, 1, 2 and 5 mg/ml) and the blood was tested for RBC aggregation via
      our computerized Myrenne Aggregometer (at Hct = 40%). Besides other routine
      laboratory parameters, fibrinogen levels were measured. In a substudy for CORE
      Trial, the hemorheological effects of RheothRx infusion was studied. Seven
      patients (mean age: 63 +/- 13 yrs) admitted with AMI and randomized for CORE
      Trial were studied. The samples were collected after admission, at 12, 24, 48
      hours, and at day 8 and 35. In vitro we found a significant (p < 0.05 or better)
      concentration-related decrease of RBC aggregation from 0.5 mg/ml drug
      concentration in the admission (both groups) and in the 48 hour (AMI) samples, in
      AMI patients with a mean decrease of 7 and 5% at 0.5 mg/ml, 13 and 8% at 1 mg/ml,
      22 and 19% at 2 mg/ml and 39 and 33% at 5 mg/ml plasma concentration of the drug.
      In the CORE Trial patients hemorheological parameters (plasma and whole blood
      viscosity, RBC aggregation and fibrinogen level) decreased during and after the
      administration of RheothRx, but after 2-8 days their values returned to the
      baseline level. These findings indicate that this agent can significantly reduce
      RBC aggregation and other hemorheological parameters, and thus suggest its
      potential usefulness in clinical states associated with increased RBC
      aggregation.

PMID- 9255436
TI  - Exercise test: trend of the leukocyte flow properties, polymorphonuclear membrane
      fluidity and cytosolic Ca2+ content in normals, in subjects with previous acute
      myocardial infarction and in subjects with aortocoronary by-pass.
AB  - We evaluated, during an exercise test, the leukocyte flow properties, the
      polymorphonuclear leukocyte (PMN) membrane fluidity and PMN cytosolic Ca2+
      content in normals, in subjects with previous acute myocardial infarction (AMI)
      and in subjects previously submitted to a aortocoronary by-pass. Leukocyte flow
      properties were evaluated using the St. George filtrometer. Examination of the
      PMN membrane fluidity was effected employing the probe TMA-DPH; while evaluation
      of the PMN cytosolic Ca2+ content was carried out using the probe Fura 2-AM. At
      baseline, in both cardiopathic groups a significant difference in PMN filtration
      parameters and in PMN cytosolic Ca2+ content was evident compared to normals. In
      normals, at peak of exercise, there was an evident reduction of mononuclear
      filtration parameters, while during recovery a slight increase of the PMN
      cytosolic Ca2+ content was observed. In subjects with previous AMI and in
      subjects with aortocoronary by-pass, however, we observed, at peak of exercise, a
      decrease of the mononuclear filtration parameters, a reduction of the PMN
      membrane fluidity and an increase of the PMN cytosolic Ca2+ content. In both
      groups, the changes in PMN membrane fluidity and cytosolic Ca2+ content remained
      during recovery. The trend of the PMN membrane fluidity and cytosolic Ca2+
      content found in the cardiopathic subjects during the exercise test suggest the
      PMN activation may be more evident in these subjects.

PMID- 9255438
TI  - Cutaneous warts.

PMID- 9255437
TI  - Myths, fables and even truths about warts and human papillomavirus.

PMID- 9255439
TI  - Epidermodysplasia verruciformis. Immunological and nonimmunological surveillance
      mechanisms: role in tumor progression.

PMID- 9255440
TI  - Role of HPV in cutaneous premalignant and malignant tumors.

PMID- 9255441
TI  - Latent and subclinical HPV external anogenital infection.

PMID- 9255442
TI  - Anogenital warts.

PMID- 9255443
TI  - Anogenital warts in children.

PMID- 9255444
TI  - Anogenital premalignant and malignant tumors (including Buschke-Lowenstein
      tumors).

PMID- 9255445
TI  - Cervical and vaginal HPV infections.

PMID- 9255447
TI  - Role of human papillomaviruses in cancer of the respiratory and upper digestive
      tract.

PMID- 9255446
TI  - HPV-associated diseases of oral mucosa.

PMID- 9255449
TI  - Cutaneous and genital HPV-associated lesions in HIV-infected patients.

PMID- 9255448
TI  - HPV infections and immunosuppression.

PMID- 9255450
TI  - Therapy of cutaneous warts.

PMID- 9255451
TI  - Therapy of anogenital HPV-induced lesions.

PMID- 9255452
TI  - Reflecting on developments in occupational dermatitis.

PMID- 9255453
TI  - Patch testing in systemic drug eruptions.

PMID- 9255454
TI  - Contact allergens--what's new? Cosmetic dermatitis.

PMID- 9255455
TI  - Contact allergens--what's new? Preservatives.

PMID- 9255456
TI  - Contact allergens--what's new? Fragrances.

PMID- 9255457
TI  - Contact allergens--what's new? Metals.

PMID- 9255458
TI  - Contact allergens--what's new? Medication-induced contact reactions.

PMID- 9255459
TI  - Contact allergens--what's new? Corticosteroids.

PMID- 9255460
TI  - Plastics/acrylics: material safety data sheets need to be improved.

PMID- 9255462
TI  - Mechanisms in irritant contact dermatitis.

PMID- 9255461
TI  - Ingested food in systemic allergic contact dermatitis.

PMID- 9255463
TI  - What's new in irritant dermatitis.

PMID- 9255464
TI  - Occupational dermatitis--what's new? Metalworking industry.

PMID- 9255465
TI  - Occupational dermatitis--what's new? Catering industry.

PMID- 9255466
TI  - Occupational dermatitis--what's new? Hospital workers.

PMID- 9255467
TI  - Occupational dermatitis--what's new? Electronics industry.

PMID- 9255468
TI  - Occupational dermatitis--what's new? Office environment.

PMID- 9255469
TI  - Pigmented contact dermatitis.

PMID- 9255470
TI  - Contact dermatitis due to topical traditional Chinese medication.

PMID- 9255471
TI  - Phytodermatitis.

PMID- 9255472
TI  - Photopatch testing.

PMID- 9255473
TI  - Mechanisms in contact urticaria.

PMID- 9255474
TI  - Agents causing contact urticaria.

PMID- 9255475
TI  - Predictive testing in contact dermatitis. Irritant dermatitis.

PMID- 9255476
TI  - Predictive testing in contact dermatitis. Allergic contact dermatitis.

PMID- 9255477
TI  - Prognosis of contact and occupational dermatitis.

PMID- 9255478
TI  - Preventive measures in contact dermatitis.

PMID- 9255479
TI  - Dermatitis in Ecuadorean farm workers.
AB  - Using a cross-sectional survey of potato farm workers in northern Ecuador, we
      examined the relationship between pesticide exposure and skin disorders. From a
      farm population census, all pesticide applicators and 1/2 of exposed field
      workers were selected. Controls were age-matched from urban occupations.
      Individual exposure measures included overall years and current hours working
      with pesticides. Farm-level measures included numbers of applications over the
      last 6 months and an application practices score (range 0-4). Each participant
      underwent a clinical skin examination, with patch tests to maneb on a sample of
      dermatitis cases. Exposure-related increases in conjunctivitis (7% of
      applicators, 0% in other groups), dermatitis (68% of exposed and 55% of
      applicators versus 31% of controls, p < 0.001) and pigmentation disorders (25% of
      exposed and applicators vs 10% controls, p = 0.06) were found. Among dermatitis
      cases (n = 117), 5% were positive to maneb on patch testing. In logistic
      regression analysis, significant predictors (p < 0.1) of dermatitis included
      years using fungicides (OR = 1.12 per year) and poor application practices (OR =
      1.42 per score unit). Agricultural fungicide application in high-exposure
      situations can contribute to dermatitis prevalence among farm populations.

PMID- 9255480
TI  - Contact allergenic activity of Tween 80 before and after air exposure.
AB  - Tween 80 is an ethoxylated hydrophilic non-ionic surfactant, which is used for
      the preparation of oil-in-water emulsions in pharmaceutical products, cosmetics,
      and industrial detergents. Ethoxylated surfactants are polyethers and are thus
      easily oxidized by atmospheric oxygen to a variety of hydroperoxides, peroxides
      and carbonyl compounds. The aim was to investigate the formation of oxidation
      products and the allergenic potential of Tween 80 before and after air exposure.
      The formation of peroxides and formaldehyde was followed with chemical analyses
      during air and pure oxygen exposure of water solutions of Tween 80 of technical
      quality. A complex mixture of compounds was formed when Tween 80 was oxidized.
      Formaldehyde was detected in amounts that may be eliciting in allergic
      individuals. Acetaldehyde was identified in Tween 80 before oxygen exposure,
      whereafter the amount gradually decreased. The contact allergenic activity was
      determined in experimental sensitization studies in guinea pigs. Non-oxidized as
      well as oxidized Tween 80 of technical quality showed allergenic activity. The
      results indicate that allergens are present in Tween 80 before oxidation and that
      new allergens are formed in the oxidation process. No obvious dose-response
      relationship was found in the sensitization studies. The possibility that
      allergenic compounds can be formed during storage and handling of products
      containing ethoxylated surfactants should be taken into consideration.

PMID- 9255481
TI  - Effect of a topical corticosteroid, a retinoid and a vitamin D3 derivative on
      sodium dodecyl sulphate induced skin irritation.
AB  - Exposure of the skin to sodium dodecyl sulfate (SDS) leads to disruption of
      barrier and skin irritation. We used repetitive short exposure to a low molarity
      SDS solution as an in vivo model to mimic the development of irritant contact
      dermatitis. In this model, we studied clinical (erythema), functional
      (transepidermal water loss(TEWL)) and cell biological changes. 24 healthy
      volunteers were patch tested with SDS (0.2%) for 4 h a day for 5 consecutive
      days. After removal of the patches, the exposed sites were treated 1 X daily
      either with a topical corticosteroid (triamcinolon acetonide cream 0.05%), a
      retinoid (tretinoin cream 0.025%), or a vitamin D3 derivative (calcipotriol
      ointment 50 micrograms/g). Irritant reactions were assessed by erythema scoring
      and measurement of barrier function with TEWL up to 14 days after the first
      challenge. Skin biopsies were taken for cell biological changes at day 4. Vehicle
      treated sites served as controls. Repetitive exposure of human skin to SDS
      resulted in a gradual increase in erythema scoring and TEWL associated with the
      upregulation of proliferative cells as measured by the expression of Ki-67
      antigen and of differentiation markers, visualized by increased expression of
      involucrin and epidermal-fatty-acid binding protein (E-FABP). Skin irritation as
      assessed by erythema scoring and TEWL was not significantly suppressed by
      triamcinolone cream. However, a significant reduction of the number of cycling
      keratinocytes and a decrease in involucrin positive cell layers was observed in
      this group. Neither treatment with calcipotriol ointment nor with tretinoin cream
      induced improvement of skin irritation as judged by visual scoring and TEWL. In
      contrast to steroid treatment, no significant effect of calcipotriol ointment or
      tretinoin cream treatment was observed with regard to the number of cycling cells
      and differentiation markers. Further studies are needed to assess whether
      treatment with topical corticosteroids is an effective modality in skin
      irritation and irritant contact dermatitis.

PMID- 9255482
TI  - Concomitant contact dermatitis due to textile dyes and to colour film developers
      can be explained by the formation of the same hapten.
AB  - p-phenylenediamine derivatives are widely used in industry and in cosmetics, and
      several of them are well-known sensitizers. One group of allergenic p
      phenylenediamine derivatives are used as colour film developers. Cross-reactivity
      between the colour film developers has been reported. In this paper, an
      occupational facial dermatitis due to colour film developers is described. The
      patient reacted to colour film developers (CD-1, CD-2, CD-3, and CD-4), but not
      to other p-phenylenediamine derivatives tested. He also showed allergic reactions
      to Disperse Blue 106 and Disperse Blue 124 and to Disperse Red 17, but not to
      Disperse Orange 3. The activation of the colour film developers by oxidation at
      physiological pH was analysed with chemical methods, and the mechanism
      responsible for the concomitant reactivities to the colour film developers and
      the disperse dyes at a molecular level is discussed.

PMID- 9255484
TI  - Contact dermatitis in a chimney sweep.

PMID- 9255483
TI  - Allergic contact dermatitis from grasses.
AB  - This study attempts to demonstrate the existence of allergic contact dermatitis
      from grass, and to develop a patch test series to screen patients with grass
      intolerance. 6 common grass species from lawns and military training areas were
      collected. Solvent extracts of polar, non-polar and volatile fractions were
      prepared and used for patch testing in 20 control subjects and 46 patients with a
      history of grass intolerance. The 20 controls had negative responses to patch
      testing. 5 out of 46 patients had positive patch tests to Axonopus compressus
      (carpet grass), Ischaemum muticum (seashore centipede grass), Imperata cylindrica
      (lalang), Panicum maximum (Guinea grass) and Pennisetum purpureum (elephant
      grass). Reactions to the non-polar fraction for all 5 species were noted. This
      study demonstrates the existence of allergic contact dermatitis from various
      common species of grass. In our series, this is seen in 11% of those with a
      history of grass intolerance.

PMID- 9255485
TI  - Contact sensitization to preservatives in children.

PMID- 9255486
TI  - Sensitization to pepper (Capsicum annuum) in a latex-allergic patient.

PMID- 9255487
TI  - Pigmented contact dermatitis due to Naphthol AS in a pillowcase.

PMID- 9255488
TI  - Occupational contact dermatitis from anethole in food handlers.

PMID- 9255489
TI  - Pseudo flautist's lip: allergic contact cheilitis from geraniol.

PMID- 9255490
TI  - Contact sensitivity to 1-(4-(2-chloroethyl)phenyl)-2-chloroethanol in a polymer
      chemist.

PMID- 9255491
TI  - Role of allergic contact dermatitis in rosacea.

PMID- 9255492
TI  - Allergic contact dermatitis from oleyl alcohol in lipstick cross-reacting with
      ricinoleic acid in castor oil and lanolin.

PMID- 9255493
TI  - Relapse of colophony dermatitis from lottery tickets.

PMID- 9255494
TI  - Reactivity to nicotine patches wrongly blamed on contact allergy.

PMID- 9255495
TI  - Simultaneous contact sensitivity due to lidocaine and crotamiton.

PMID- 9255496
TI  - Patch testing with lower concentrations of chromate and nickel.

PMID- 9255497
TI  - Lack of contact allergy in consecutive women with vulvodynia.

PMID- 9255498
TI  - Crescendo reactions to sodium lauryl sulfate and retinoic acid in irritant patch
      tests.

PMID- 9255500
TI  - Occupational allergic contact dermatitis caused by acrylic tri-cure glass
      ionomer.

PMID- 9255499
TI  - Contact dermatitis in psoriasis due to propolis.

PMID- 9255501
TI  - Maintenance of hand eczema by oral pantothenic acid in a patient sensitized to
      dexpanthenol.

PMID- 9255502
TI  - A dermatitis flare after patch testing with Dermatophagoides pteronyssinus in an
      atopic patient.

PMID- 9255503
TI  - Mechanisms of lymphocyte adhesion to cultured human corneal epithelial cells.
AB  - PURPOSE: The authors studied the adhesion mechanisms between peripheral blood
      lymphocytes (PBL) and cultured human corneal epithelial (HCE) cells to
      investigate the lymphocyte interaction with corneal epithelial cells in the
      corneal immune response. METHODS: First, the authors examined the expression of
      intercellular adhesion molecule (ICAM)-1 or lymphocyte function-associated
      antigen (LFA)-3 on the normal human corneal epithelium and cultured HCE cells by
      an immunostaining technique and flow cytometry. Effects of inflammatory cytokines
      such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, on ICAM-1
      or LFA-3 expression on cultured HCE cells were also examined. Second, the authors
      performed an adhesion assay with 51Cr-labeled monocyte-depleted PBL from normal,
      healthy volunteers and cultured HCE cells, with and without treatment of IFN
      gamma or TNF-alpha in 96-well-plates for 1 hour at 37 degrees C in 5% CO2. After
      unbound PBL were removed, the radioactivity of the sample in each well was
      counted with a scintillation counter. In addition, the authors evaluated the
      blocking effects of monoclonal antibodies (mAbs) on the adhesion of PBL to the
      cultured HCE cells. RESULTS: ICAM-1 expression was not detected in the normal
      human corneal epithelium. However, the expression of ICAM-1 was detected on the
      cultured HCE cells with Dulbecco's Modified Eagle Medium supplemented with 10%
      fetal bovine serum. In addition, both IFN-gamma and TNF-alpha increased ICAM-1
      expression on the cultured HCE cells dramatically. LFA-3 expression was detected
      in all cell layers of the normal human corneal epithelia. Neither IFN-gamma nor
      TNF-alpha had any effect on LFA-3 expression on the cultured HCE cells. The PBL
      adhesion to the HCE cells with and without treatment of IFN-gamma or TNF-alpha
      was blocked dominantly by anti-ICAM-1 or anti-LFA-1 alpha mAb. Anti-LFA-3 mAb
      also blocked the PBL adhesion but had less blocking effect than anti-ICAM-1 or
      anti-LFA-1 alpha mAb. Anti-very late activation antigen beta, or anti-human
      leukocyte antigen (HLA)-class I or HLA-class II mAb had no effect on the PBL
      adhesion to the HCE cells. The adhesion percentile of the PBL applied to the HCE
      cells pretreated with IFN-gamma or TNF-alpha showed a dose-response curve
      dependent on the concentration of these cytokines. CONCLUSIONS: The results in
      the present study demonstrate that (i) adhesion of lymphocytes to HCE cells could
      be mediated by the LFA-1-ICAM-1 pathway and/or the CD2-LFA-3 pathway; (ii) the
      LFA-1-ICAM-1 pathway could be crucial in lymphocyte adhesion to HCE cells; (iii)
      IFN-gamma or TNF-alpha exerts an enhancing effect not only on the ICAM-1
      expression on HCE cells but also on the adhesion of lymphocytes to HCE cells.

PMID- 9255504
TI  - Physiological transport properties of cultured retinal microvascular endothelial
      cell monolayers.
AB  - PURPOSE: To characterize baseline transport properties: hydraulic conductivity
      (Lp), albumin permeability (Pe), and transendothelial electrical resistance (TER)
      of bovine retinal microvascular endothelial cells (RMEC) in the development of an
      in vitro model of the blood-retinal barrier (BRB). METHODS: RMEC were grown on
      porous, polycarbonate filters for determination of the number of days required to
      achieve minimal transport rates. Lp, Pe, and TER were measured by utilizing a
      bubble tracking spectrophotometer, by quantifying the diffusional movement of
      fluorescein isothiocyanate-labeled albumin, and by utilizing a Millipore
      electrical resistance meter, respectively. RESULTS: Lp decreased significantly
      from 7.82 +/- 0.85 x 10(-7) (mean +/- SEM) cm/sec/cm H2O at post-plating Day 5 to
      1.44 +/- 0.26 x 10(-7) cm/sec/cm H2O at Day 9. Pe of the monolayer also decreased
      progressively with days post-plating from 3.44 +/- 0.53 x 10(-6) cm/sec at Day 7
      to a minimum of 1.95 +/- 0.29 x 10(-6) cm/sec at Day II. Peak TER fluctuated
      until Day 7, when it began to steadily increase from 17.14 ohm-cm2 to a peak
      value of 25.42 ohm-cm2 at Day 10, decreasing from then on to 22.24 ohm.cm2 on Day
      12. Known disrupters of the BRB, NECA and VEGF, elicited significant increase in
      RMEC Lp showing the sensitivity of this model to pharmacological alterations.
      CONCLUSIONS: Our data indicate that RMEC grown on polycarbonate filters form a
      restrictive monolayer of cells, which exhibit dynamic alterations in response to
      pharmacological agents, thus demonstrating an in vitro model of the BRB. Future
      studies with the model may offer insights into the pathogenesis of retinal
      vascular diseases and allow convenient testing of pharmacological interventions.

PMID- 9255506
TI  - Protein-lipid interaction on the surface of a hydrophilic contact lens in vitro.
AB  - PURPOSE: To investigate the mechanism of protein-lipid interactions responsible
      for biofilm formation on the surface of hydrophilic contact lenses in vitro.
      METHODS: New, never-worn hydrophilic contact lenses were individually incubated
      in a protein-only, lipid-only, or combination protein-lipid artificial tear
      solution for 24 hours at 37 degrees C with constant stirring. Deposited lipids
      were removed with a methanol based extraction procedure, separated using high
      performance, thin layer chromatography and quantitatively analyzed
      densitometrically. Deposited proteins were extracted with 4M urea, separated
      using gel electrophoresis and quantitatively analyzed densitometrically. RESULTS:
      The presence of protein in the artificial tear solution has a profound effect on
      the nature of lipid deposition for each group of hydrophilic lens, whereas the
      presence of lipid has a significant effect on the nature of protein deposition
      for only a group IV lens. In addition, the presence of lipid deposits on a group
      IV lens decreases the adsorption of lysozyme, while the presence of protein
      deposits reduces the amount of total lipid adhering to a group II lens.
      CONCLUSIONS: Protein adsorption on a group IV lens renders the lens surface less
      hydrophilic and, thereby, more susceptible to lipid deposition, which in turn
      increases surface hydrophobicity and inhibits additional protein deposition. For
      a group II lens, positively charged protein competes with and replaces some of
      the polar lipids attached to the lens. Thus, the interaction of protein and lipid
      on a lens surface most prone to a particular contaminant apparently makes it less
      likely for that contaminant to bind.

PMID- 9255505
TI  - Effect of 5-methylurapidil, an alpha 1a-adrenergic antagonist and 5
      hydroxytryptamine1a agonist, on aqueous humor dynamics in monkeys and rabbits.
AB  - PURPOSE: To evaluate the effects of 5-methylurapidil (5-MU) on intraocular
      pressure (IOP) and aqueous humor dynamics in female cynomolgus monkeys and albino
      rabbits. METHODS: IOP was measured by pneumatonometer prior to and up to 6 hours
      after AM administration of 5-MU to one eye of each of 8 normal monkeys and to the
      laser-induced glaucomatous eye of 8 monkeys. During single-dose and 5-day
      multiple-dose testing, pupillary diameter (PD) was measured at the same time and
      same intervals as IOP measurements in the normal monkeys. Outflow facility and
      aqueous humor flow rates were measured in 8 normal monkeys before and after
      treatment. Uveoscleral outflow was measured in 8 rabbits before and after
      treatment. RESULTS: In normal monkeys, unilateral topical application of 2 x 25
      microliters of 1% or 2% 5-MU significantly (p < 0.05) reduced pupil size and IOP
      bilaterally as compared to baseline measurements. The reduction in IOP (mean +/-
      SEM, mmHg) was up to 2.8 +/- 0.7 (1% 5-MU) and 4.4 +/- 0.5 (2% 5-MU) in the
      treated eyes, and 2.3 +/- 0.8 (1%) and 3.0 +/- 0.7 (2%) in the contralateral
      eyes. In glaucomatous monkeys, the maximum reduction in IOP was 6.5 +/- 1.0 mmHg
      (1%) and 7.5 +/- 0.8 mmHg (2%). The ocular hypotensive effect increased over time
      with twice-daily administration for 5 days. Compared with baseline values,
      outflow facility and aqueous flow rates in the treated eyes of normal monkeys
      were increased (p < 0.01) by 51% and by 11%, respectively. Uveoscleral outflow
      was unaltered (p > 0.3) in rabbits compared with baseline values. Mild corneal
      edema, corneal punctate erosions, and conjunctival discharge occurred in some
      eyes treated with either 1% or 2% 5-MU. CONCLUSIONS: 5-Methylurapidil, an
      antagonist at the alpha 1A-adrenergic receptor subtype and an agonist at the 5
      HT1A receptor subtype, lowers IOP predominantly by increasing outflow facility
      and may have potential for the therapy of glaucoma.

PMID- 9255507
TI  - Human T-cell lymphotropic virus type 1 can infect primary rat retinal glial cells
      and induce gene expression of inflammatory cytokines.
AB  - PURPOSE: To examine whether or not retinal glial cells can be infected by human T
      cell lymphotropic virus type 1 (HTLV-1) and test the possibility that HTLV-1
      infected retinal glial cells are involved in the pathogenesis of HTLV-1 uveitis
      (HU). METHODS: We tested infection of HTLV-1 by a standard coculturing method
      using WKAH rat retinal glial cells and irradiated MT-2, a human T cell line that
      produces HTLV-1. Infection was confirmed by detecting the integrated HTLV-1
      provirus, using polymerase chain reaction (PCR), viral gene expression, using
      reverse transcriptase-PCR (RT-PCR) and HTLV-1 p19 ELISA, and by identifying the
      HTLV-1-infected glial cells by immunofluorescence cytochemistry and in situ
      hybridization. Changes in cytokine gene expression were studied by RT-PCR.
      RESULTS: Using a semiquantitative PCR of HTLV-1 provirus sequence, we found that
      2.6% of the retinal glial cells were infected at 3 days after infection, followed
      by a gradual decrease in the percentage with an extended period of culture up to
      4 weeks. This time course of infection was also verified by RT-PCR and ELISA
      studies that detect viral mRNA expression and protein production, respectively.
      Expression of HTLV-1 gag protein and tax mRNA was detected in a part of glial
      cells by indirect immunofluorescence cytochemistry and in situ hybridization,
      respectively. RT-PCR analysis of cytokine gene expression revealed that gene
      expression of IL-6, CINC-1 (Gro, KC), and TNF-alpha were induced in these cells,
      with a peak at 3 weeks after infection. CONCLUSION: These results provided
      supportive evidence for the theory that the infection of retinal glial cells by
      HTLV-1 and subsequent production of inflammatory cytokines could be one
      contributing factor for the development of the unique clinical features of HU. A
      better understanding of the specific roles of the inflammatory cytokines in the
      pathogenesis of HU would be beneficial in the treatment and control of this
      disease.

PMID- 9255508
TI  - The immunohistochemical composition of corneal basement membrane in keratoconus.
AB  - PURPOSE: Keratoconus is a gradually progressing disease of unknown cause,
      characterized by central thinning, increased curvature, and finally scarring of
      the cornea. This causes myopia and astigmatism and the ultimate treatment is
      keratoplasty. We studied the composition of basement membranes (BMs) in normal,
      scarred and keratoconus corneas to find out possible changes specific for
      keratoconus. METHODS: Frozen sections of normal, scarred and keratoconus corneas
      were immunostained with various antibodies against basement membrane (BM)
      proteins and integrin beta 4. RESULTS: In the keratoconus corneas, we found
      discontinuities or defects in Bowman's layer, sometimes distorted stroma beneath
      the defects, and also thinning of the stroma. The results show that within the
      defects in keratoconus corneas, there is an expression of proteins that are not
      normally present in the corneal BM, i.e. collagen alpha 1/2 (IV) chains, and on
      the contrary, absence of the expression of some proteins, i.e. collagen alpha 5-6
      (IV) chains that normally are continuously expressed in the corneal epithelial
      BM. In addition, either increased or decreased expression of laminin-1 (alpha 1
      beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2) and collagen type VII,
      depending on the keratoconus defect, was seen and the expression of integrin beta
      4 was decreased. These findings seem to be specific for keratoconus, as they were
      not found in scarred corneas. CONCLUSIONS: The results show that the defects in
      BM and changes in the BM composition are involved in the pathogenesis of
      keratoconus. Furthermore, it seems that scarring alone does not explain the
      breaks in Bowman's layer and immunohistochemical changes seen in keratoconus.
      Therefore, we suggest that a process similar to wound healing, which is initiated
      by breaks in Bowman's layer, would largely contribute to the differences seen in
      keratoconus corneas.

PMID- 9255509
TI  - Harvest and storage of adult human retinal pigment epithelial sheets.
AB  - PURPOSE: To describe a method for the harvesting and storing of intact viable
      sheets of adult human retinal pigment epithelial (RPE) cells. METHODS: Adult
      human RPE cells were harvested as intact sheets from 21 cadaver eyes, using the
      enzyme Dispase. The sheets were embedded in 50% gelatin containing 300 mM sucrose
      and stored at 4 degrees C. The viability of the cells, as well as their ability
      to proliferate in vitro, was studied for 96 hours after harvesting. Light
      microscopy (LM), transmission (TEM) and scanning electron microscopy (SEM) were
      performed to determine the integrity and ultrastructural features of the cells.
      Microbiologic culture of the harvested sheets was performed to exclude
      contamination. RESULTS: LM, TEM and SEM showed intact RPE cells with well
      developed microvilli, basal infoldings and intercellular connections. The initial
      viability of intact RPE sheets was 86%, with a progressive decline in viability
      with increased storage time. Cells harvested within 24 hours after death
      maintained greater viability than those harvested after 24 hours (p < 0.05).
      Harvested RPE cells were free of microbial contamination and rapidly proliferated
      when cultured in vitro. CONCLUSION: Intact sheets of adult human RPE can be
      isolated using the enzyme Dispase. The cells appeared suitable for retinal
      transplantation if harvested within 24 hours of death and maintained 82%
      viability for as long as 48 hours if stored at 4 degrees C.

PMID- 9255510
TI  - Polymorphonuclear leukocyte cells and elastase in tears.
AB  - PURPOSE: To characterize the effects that mode of sampling and overnight eye
      closure have on the nature of caseinolytic activity recovered in tear fluid.
      METHODS: Reflex, open and closed (R, O and C) eye tear fluids were collected by
      microcapillary tubes or from the inferior formix by Schirmer strip.
      Microcapillary collected samples were centrifuged and recovered cells
      cytochemically characterized and probed by immunofluorescence microscopy, or
      alternatively extracted in acidic PBS. Tear supernatants, pellets and Schirmer
      strip extracts were subjected to casein zymography or SDS-PAGE and immunoprobed
      for plasmin/plasminogen. To identify caseinolytic activity, samples were
      immunoprecipitated with antibodies to plasmin/plasminogen or to elastase, and the
      immunoprecipitated materials were subjected to zymographic analysis. RESULTS:
      Immunoblot assays revealed R and O samples contained low levels of plasminogen
      (approximately 1.1 micrograms/ml) and only trace levels of plasmin (< 0.1 ng/ml).
      Insufficient levels of caseinolytic activity were present to allow zymographic
      detection. Cytochemical analysis revealed that R and O pellets consisted almost
      exclusively of desquamated epithelium. Immunoblot analysis revealed that C fluid
      was associated with an increase in plasminogen and its partial conversion to
      plasmin (approximately 3.2 ng/ microliter), high molecular weight covalent
      complexes and degradative products. Zymographic analysis disclosed much greater
      caseinolytic activity than could be attributed to plasmin or its cleavage
      products. This consisted primarily of three bands (30-26 kDa) which were
      identified as polymorphonuclear leukocyte (PMN) cell elastase based on size and
      antigenicity. This is derived from PMNs recovered from the C pellet. Elastase
      could also be recovered from Schirmer strips from 90% of donors, provided that
      the strips were extracted in sample loading buffer. The activity was restricted
      to the portion of the strip that had been in contact with the ocular tissue.
      CONCLUSIONS: The main source of caseinolytic activity in C fluid is elastase.
      This arises from PMNs that undergo recruitment, activation and degranulation in
      the C environment. In contrast, the elastase recovered in Schirmer strip extracts
      is derived from intact PMNs that adhere to the strip during sample collection.
      This would suggest that PMN cells undergo a low level of recruitment into the
      open eye environment.

PMID- 9255511
TI  - Limbal conjunctival Langerhans cell density in ocular cicatricial pemphigoid: an
      indirect immunofluorescence study on Dispase-split conjunctiva.
AB  - PURPOSE: To evaluate limbal conjunctival Langerhans cell density in ocular
      cicatricial pemphigoid patients versus normal controls. Langerhans cells
      obviously play a major role in T-cell activation and are involved in corneal and
      conjunctival inflammatory diseases. METHODS: We used a protease (Dispase II) on
      inferior limbal conjunctival biopsies to separate the epithelium from the
      substantia propria and performed indirect immunofluorescence to analyze CD1a+ (a
      specific Langerhans cell surface antigen) cell density on flat-mounted epithelial
      sheets obtained from 30 normal controls and 11 patients presenting with ocular
      cicatricial pemphigoid. RESULTS: This technique was quick and reproducible. The
      mean Langerhans cell density in normal limbal conjunctiva was 272 +/- 37
      cells/mm2. It was significantly higher in ocular cicatricial pemphigoid patients:
      386 +/- 43 cells/mm2 (p = 0.001). CONCLUSIONS: Conjunctival Langerhans cell
      density in ocular surface inflammatory diseases can best be evaluated by indirect
      immunofluorescence, following epithelial sheet separation from the substantia
      propria, using Dispase II.

PMID- 9255512
TI  - Platelet-derived growth factor-BB (PDGF-BB) in tear fluid: a potential modulator
      of corneal wound healing following photorefractive keratectomy.
AB  - PURPOSE: To measure the pre- and postoperative tear fluid platelet-derived growth
      factor-BB (PDGF-BB) concentrations of patients undergoing excimer laser
      photorefractive keratectomy (PRK). METHODS: Tear fluid samples from PRK patients
      were collected with scaled microcapillary tubes preoperatively (Day 0, N = 23),
      on the second (Day 2, N = 24) and on the seventh (Day 7, N = 14) postoperative
      days. The PDGF-BB concentration was measured using a sandwich enzyme immunoassay,
      and the PDGF-BB release was calculated by multiplying the concentration by the
      tear fluid flow in the collection capillary. RESULTS: The mean tear fluid flow in
      the capillary was 17.4 microliters/ min (range 1.4-55.0) on Day 0, 62.6
      microliters/min (4.3-125.0, p = 0.0000) on Day 2, and 15.5 microliters/min (1.2
      50.0, NS) on Day 7. Seventeen percent (4/23) of the Day 0 samples contained
      detectable concentrations of PDGF-BB (range 95-1330 ng/l). On Day 2 all (24/24)
      tear samples showed significantly increased concentrations (mean 507 ng/l, range
      45-2280 ng, p = 0.0001) and releases (mean 27.6 pg/min, range 1.0-98.0; p =
      0.0000). On Day 7 PDGF-B was still measurable in 9/14 samples (mean concentration
      194 ng/l, range < 5-925 ng/l, and mean release 1.9 pg/min, range 0.04-6.8
      pg/min). CONCLUSIONS: PDGF-BB is an inducible component of tear fluid. In spite
      of hypersecretion caused by the corneal wound, PDGF-BB concentrations raised
      significantly during the initial wound healing. Increased PDGF-BB release during
      the two postoperative days following PRK suggests a role in corneal wound
      healing.

PMID- 9255513
TI  - Effect of pretreatment of germanium-132 on Na(+)-K(+)-ATPase and galactose
      cataracts.
AB  - PURPOSE: Recently, we reported that topical administration of 2-carboxyethyl
      germanium sesquioxide (Ge-132) concurrently with 50% galactose feeding delayed
      the establishment of mature cataracts and reduced advance glycation product. This
      study was to determine the effect of pretreatment of Ge-132 on galactose
      associated morphological changes and Na(+)-K(+)-ATPase activity. METHODS: Young
      Sprague Dawley rats received topical eye drops four times a day of either saline
      or Ge-132 seven days prior to the 50% galactose diet and during galactose
      feeding. At desired intervals the lenses were extracted, photographed and
      processed for either light microscopy, scanning electron microscopy or the
      determination of Na(+)-K(+)-ATPase activity. RESULTS: In Ge-132 pretreated lenses
      as compared to saline pretreated lenses the following results were observed: (a)
      the galactose-induced morphological alterations in the majority of lenses were
      delayed and (b) Na(+)-K(+)-ATPase activity was protected. CONCLUSIONS: Our
      previous and current studies show that in addition to osmotic stress post
      translational protein modification, such as glycation, including enzymes may play
      a role in initiating changes that lead to cataract development. The inhibition of
      protein glycation by antiglycating compounds, such as Ge-132, delays sugar
      cataract formation. Currently, we are investigating the status of protein
      glycation and advanced glycation end products following pretreatment with Ge-132
      and the role of Ge-132 on the activities of enzymes such as aldose reductase and
      Na(+)-K(+)-ATPase.

PMID- 9255514
TI  - Quantification and regulation of mRNAs encoding beaded filament proteins in the
      chick lens.
AB  - PURPOSE: To quantify the expression of beaded filament protein mRNA levels in
      regions of the chick lens and to examine the in vitro regulation of message and
      protein levels using cell culture techniques. METHODS: RNase protection assays
      and Northern blotting were used to quantify beaded filament protein mRNA levels
      in dissected lenses. Cultured cells were assayed for mRNA with RNase protection
      and for protein with Western blotting and ELISA techniques after treatment with
      cAMP analogs. RESULTS: Beaded filament protein message levels were greatly up
      regulated in cortical fiber cells compared to annular pad cells. Full length
      messages were also detected in nuclear fiber cells. The presence of an unusual
      form of the CP49 message with a lamin-like insert, CP49INS, was also established.
      Both message and protein levels were subject to regulation in response to
      elevated intracellular cAMP levels. CONCLUSIONS: The accumulation of beaded
      filament protein levels during fiber cell development may be due to the increased
      cAMP-mediated transcription of message. The presence of CP49INS may lend new
      insight into mechanisms of intermediate filament assembly.

PMID- 9255515
TI  - Intracellular calcium mobilization following prostaglandin receptor activation in
      human ciliary muscle cells.
AB  - PURPOSE: To investigate the presence of specific prostaglandin receptors in
      primary cultures of human ciliary muscle cells by measuring agonist-stimulated
      intracellular calcium mobilization. METHODS: The ciliary muscle cells, cultured
      from postmortem human ciliary muscle explants, were first characterized by anti
      desmin and anti-smooth muscle alpha-actin antibodies. Increase in intracellular
      calcium concentrations, in fura 2-AM loaded human ciliary muscle cells stimulated
      by prostaglandin receptor agonists, were determined with a digital fluorescence
      imaging system. RESULTS: The resting intracellular calcium concentration in the
      fura 2-AM loaded cells was 60.0 +/- 6.0 nM. The threshold concentration of PG
      receptor agonists needed to increase the concentration of intracellular calcium
      was 10(-8) M. The stimulation of these cells by PGF2 alpha, 17-phenyl trinor
      PGE2, and U46619, the FP, EP1, and TP receptor agonists, resulted in the dose
      dependent increase of intracellular calcium. CONCLUSION: The results of the
      present study suggest that EP1, FP, and TP receptors are present in human ciliary
      muscle cells.

PMID- 9255516
TI  - Identification of developmentally regulated sea urchin U5 snRNA genes.
AB  - A PCR approach was used to isolate repeated U5 small nuclear RNA (snRNA) genes
      from the sea urchin Lytechinus variegatus. A 1.3 kb repeat, LvU5.0, and three
      other variants, LvU5.1-U5.3, that differ in the coding region and in the proximal
      sequence element (PSE) region were isolated. Southern Blot analysis indicate that
      the U5 snRNA genes, unlike other embryonically expressed snRNA genes (U1, U2 and
      U6), are not found in a simple tandem repeat, but instead, exist in several
      heterogeneous clusters each with a small number of genes. The U5 PSE has limited
      sequence similarity with the other sea urchin PSEs. However, when used in a
      mobility shift assay the U5 PSE forms a protein/DNA complex that is very similar
      to the complex formed with the U6 PSE. An RNase protection assay used to monitor
      the accumulation of U5 snRNA during development shows that at least two U5
      variants are coordinately expressed during embryogenesis.

PMID- 9255517
TI  - Nucleotide sequence of the Treponema pallidum eno gene.
AB  - We determined the nucleotide sequence of the enolase (eno) gene of Treponema
      pallidum, the noncultivable agent of syphilis. The deduced amino acid sequence of
      T. pallidum enolase (Eno) is 432 amino acids long with a predicted molecular mass
      of 46.7 kDa. The Eno amino acid sequence has a high degree of homology to the
      amino acid sequences of prokaryotic and eukaryotic Eno. This is the first eno
      sequence reported for a bacterium in the order Spirochaetales.

PMID- 9255518
TI  - Identification, sequences, and expression of Treponema pallidum chemotaxis genes.
AB  - Treponema pallidum, the agent of syphilis, is a pathogenic spirochete that has no
      known mechanisms of genetic exchange and cannot be continuously cultivated in
      vitro. A probe based on the nucleotide sequence of the T. pallidum cheA gene was
      used to screen a T. pallidum genomic DNA library. A treponemal DNA region
      containing four open reading frames (orfs) was identified. The proteins encoded
      by these orfs have significant homology with proteins involved in bacterial
      chemotaxis. The orfs have been designated cheA, cheW, cheX, and cheY. The cheA,
      cheW, and cheY genes were individually-cloned and expressed in vitro. The
      observed molecular mass of each protein correlated well with its predicted
      molecular mass. Reverse transcriptase-PCR data indicate that cheA through cheY
      are co-transcribed. The organization of these genes suggests that they comprise
      an operon. We hypothesize that the ability to sense and respond to nutrient
      gradients is important for the survival and dissemination of T. pallidum in vivo.
      The presence of a putative che operon strongly suggests that T. pallidum has the
      potential for a chemotactic response.

PMID- 9255519
TI  - Direct cycle sequencing with delta Taq DNA polymerase.
AB  - The delta Taq DNA polymerase is a new, genetically modified version of standard
      Taq DNA polymerase which lacks the 5'-->3'-exonuclease activity. The present
      study was designed to investigate the use of delta Taq DNA polymerase for direct
      cycle sequencing. Results show that delta Taq DNA polymerase can be used for
      direct cycle sequencing of the PCR amplified DNA, either from an asymmetrically
      amplified template (by PCR), double stranded DNA template, PCR amplified DNA
      cloned into a plasmid vector or from a single stranded template. The primer to
      template ratio and number of cycles necessary for best sequence data have been
      determined. From these results we conclude that delta Taq DNA polymerase is a
      highly versatile enzyme which can be used for DNA sequence determinations by
      direct cycle sequencing.

PMID- 9255520
TI  - PCR-based isolation and chromosome assignment of members of the Em gene family
      from wheat.
AB  - Four members belonging to the wheat Em gene family were isolated by PCR, cloned
      and subsequently sequenced. One of the genes corresponds perfectly to a previous
      published cDNA sequence, the other three genes are new. The amplified sequences
      contain the entire coding region, which is interrupted by a short intron of
      variable length, and part of the 3' untranslated region. The chromosomal
      assignment of each of the four sequences and three extra, previously published,
      Em sequences was determined using PCR with sequence-specific primers on wheat
      aneuploid nullitetrasomic lines. Three sequences were shown to be encoded by the
      Em-A1 locus (on chromosome 1A), one by Em-B1 on chromosome 1B and two by Em-D1 on
      chromosome 1D. Hence, primer sets specific for each of the three homoeologous
      chromosomes of the group 1 are available. A lot of DNA sequence polymorphism
      exists among the sequences most of which is found in the non-coding parts and
      mainly in the introns. Sequence alignment groups the seven known Em sequences
      irrespective of their locus origin. The implication of these findings in relation
      to the organisation and evolution of the Em gene family are discussed.

PMID- 9255521
TI  - Localization of an open reading frame with homology to human aspartoacylase
      upstream from psbA in the prokaryote Prochlorococcus marinus CCMP 1375.
AB  - An open reading frame encoding a polypeptide with significant homology (about 28%
      identity and 16% similarity) to human aspartoacylase (ASPA) was identified in the
      genome of Prochlorococcus marinus CCMP 1375, an oxyphototrophic bacterium.
      Sequence alignments show that, in particular, the regions previously suggested to
      form the catalytic core of human ASPA are evolutionarily conserved and nearly
      identical to that found in the Prochlorococcus putative ASPA. A glutamate at
      position 273 is located central to the strongly conserved INEAAY motif and
      corresponds to a glutamate-285 in human ASPA. A point mutation at this site,
      resulting in a Glu285Ala missense mutation, was identified previously as the
      molecular basis for Canavan disease, a form of leukodystrophy. The data provide
      new insights about conserved and hence functionally important domains of ASPA.
      The detection of this gene in an unicellular prokaryote demonstrates that this
      enzymatic activity is more widespread than expected previously. Furthermore,
      bacteria may be used as simple model organisms to study different forms of ASPA.

PMID- 9255522
TI  - Sequence of the VP7 gene of an atypical human rotavirus: evidence for genetic and
      antigenic drift.
AB  - The nucleotide sequence of the gene encoding the outer capsid glycoprotein, VP7,
      isolated from a reassortant human rotavirus, M3014, was determined. The deduced
      amino acid sequence exhibited significant identity to the VP7 from a standard
      strain belonging to serotype G4, although the antigenic regions of the M3014 VP7
      resembled sequences from both serotype G4 and G9 viruses. However, reactivity
      with G4 or G9 serotype-specific monoclonal antibodies was not observed. We
      suggest that the M3014 VP7 was derived from sequential mutation of a G4-like
      progenitor gene resulting in a protein with novel antigenic properties.

PMID- 9255523
TI  - An abundant zebrafish cDNA clone encodes a ras-like protein which is expressed
      ubiquitously.
AB  - An abundant clone from a zebrafish embryonic cDNA library was identified and
      sequenced. It encodes a ras-like protein, being 94-95% identical to vertebrate
      Ran, ras-related nuclear protein. The zebrafish Ran mRNA is expressed in all
      tissues examined and throughout embryogenesis; therefore, it is likely that the
      Ran protein functions in all types of cells.

PMID- 9255524
TI  - A prospective randomized trial of sclerotherapy versus ligation in the elective
      treatment of bleeding esophageal varices.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ligation (EVL) and endoscopic variceal
      sclerotherapy (EVS) are known to be equally effective in eradicating bleeding
      esophageal varices in patients with hepatic cirrhosis, but the long-term safety
      and efficacy of the two techniques have not been clearly established. The aim of
      this study was to determine the relative frequency of rebleeding, recurrence of
      varices, and survival after treatment with the two techniques during a relatively
      long follow-up period. PATIENTS AND METHODS: A total of 111 patients without
      bleeding at the index endoscopy were randomly assigned to either EVL (n = 57) or
      EVS (n = 54). After eradication of the varices, the patients received endoscopic
      examinations every three months and for each episode of rebleeding. RESULTS: The
      mean follow-up periods were 534 +/- 42 days in the EVS group and 496 +/- 40 days
      in the EVL group. The two techniques were equally effective in eradicating
      varices (93% in EVL group and 92.5% in EVS group). The mean number of sessions
      required to obtain eradication was slightly lower (mean +/- SE) in the EVL group
      (3.5 +/- 0.1 vs. 4.0 +/- 0.1, P = 0.004), while the time required for eradication
      was longer (33.8 +/- 2.1 vs. 27.3 +/- 1.4, P = 0.01). The comparison of the
      Kaplan-Meier estimates of survival and time to first rebleeding did not show any
      statistically significant differences between the two groups. The rate of
      complications was significantly higher in the EVS group than in the EVL group
      (31% vs. 11%, P = 0.001), while the rate of recurrent varices during follow-up
      was higher in the EVL group (30% vs. 13%, P = 0.03). CONCLUSIONS: While the two
      techniques are equally effective, ligation treatment shows greater advantages in
      the short-term follow-up, but is associated with more frequent recurrence of
      varices in the longer term. These two aspects should be considered for evaluation
      in the cost-benefit ratio and quality of life analysis. All patients should have
      frequent endoscopic evaluations (every three or four months) throughout the first
      year of follow-up.

PMID- 9255525
TI  - Treatment of bleeding esophageal varices with cyanoacrylate and polidocanol, or
      polidocanol alone: results of a prospective study in an unselected group of
      patients with cirrhosis of the liver.
AB  - BACKGROUND AND STUDY AIMS: Data concerning the results with emergency and further
      elective therapy of esophageal varices using polidocanol and cyanoacrylate, or
      polidecanol alone, in an unselected group of patients with liver cirrhosis have
      not previously been available. The aim of the present prospective study was to
      evaluate acute and repeated cyanoacrylate and polidocanol therapy in the
      emergency and long-term elective management of esophageal varices. METHODS: In
      accordance with the protocol of the present prospective study, acutely bleeding
      esophageal varices of grades 1 to 3 were treated endoscopically with polidocanol
      injection, while grade 4 varices, large solitary varices (over 5 mm) and
      otherwise uncontrollable cases of variceal bleeding were treated by injection of
      cyanoacrylate and polidocanol. Over a period of 62 months, 112 patients (65 men,
      47 women) with acute bleeding from esophageal varices due to cirrhosis of the
      liver (69% alcohol-related) underwent a total of 245 treatment sessions in
      hospital. The average age of the patients was 62.0 +/- 12.3 years (58.1% were 60
      or older). Hepatic function corresponded to Child-Pugh class A in 38 patients
      (33.9%), Child-Pugh class B in 68 patients (60.7%), and Child-Pugh class C in six
      (4.5%). RESULTS: Sixty-eight patients (60.7%) were treated with polidocanol
      alone, and 44 (39.3%) with cyanoacrylate and polidocanol. Acute hemostasis was
      achieved in all cases. In 5.7% of the sclerotherapy procedures, bleeding ulcers
      were observed, and a pleural effusion was seen in one case. The hospital
      mortality rate was 24.1%, resulting from the bleeding in 2.7% and due to liver
      failure in the remaining cases. Recurrent bleeding occurred within 24 hours in
      four patients (3.6%), and during the later course of the hospital stay in a
      further 11 patients (9.8%). The mean survival time was 13.7 +/- 17.7 months. Over
      the entire observation period of 23 +/- 21 months, 67 patients died (59.8%); the
      cause of death was hemorrhage in 4.5%, the underlying hepatic disease in 65.7%,
      and non-hepatic causes in 29.8%. Recurrent bleeding occurred in 58 patients
      (51.7%). The cumulative survival rate in the patients treated with cyanoacrylate
      and polidocanol was 66 +/- 15% and 26 +/- 32% after one and five years,
      respectively, and 56 +/- 13% and 33 +/- 19% in those treated with polidocanol
      alone. CONCLUSIONS: Endoscopic treatment of esophageal varices with cyanoacrylate
      and polidocanol, or polidocanol alone, is effective in controlling bleeding, and
      the complication rate is tolerable. The short-term and long-term mortality rates
      are determined largely by the underlying liver disease.

PMID- 9255526
TI  - Urinary trypsinogen-2 test strip in detecting ERCP-induced pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: We have evaluated a new urinary trypsinogen-2 test
      strip, based on the principle of immunochromatography, in the diagnosis of acute
      pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP).
      PATIENTS AND METHODS: One hundred six consecutive patients undergoing ERCP (with
      opacification of the pancreatic duct) at the Helsinki University Central Hospital
      were included in the study. Patients were tested with a urinary trypsinogen-2
      test strip six hours after ERCP. Quantitative trypsinogen-2 as well as serum and
      urine amylase values were measured before the procedure and six hours after it.
      RESULTS: In patients developing pancreatitis after ERCP, the median urinary
      trypsinogen-2 concentration six hours after the endoscopic procedure was 1780
      micrograms/l (range 29-10,700 micrograms/l), and in patients without pancreatitis
      the median concentration was 3.6 micrograms/l (range 0.1-3390 micrograms/l; P <
      0.0001). The sensitivity and specificity figures for the urinary trypsinogen-2
      test strip results in diagnosing post-ERCP pancreatitis were comparable (81% and
      97%, respectively) to those for serum amylase (91% and 96%) and urine amylase
      measurements (81% and 95%). The test strip showed a good correlation (kappa =
      0.75) with the quantitative trypsinogen-2 assay. CONCLUSIONS: The increase in
      urinary trypsinogen-2 concentration after ERCP reflects pancreatic injury, and
      can be detected by the test strip. Patients should be tested before the ERCP
      procedure as well, since elevated baseline values occur. The test is reliable and
      easy to perform even on an outpatient basis. However, its clinical usefulness
      requires evaluation in further trials.

PMID- 9255527
TI  - Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: The reason for the increased risk of pancreatitis
      after endoscopic retrograde cholangiopancreatography (ERCP) in patients with
      sphincter of Oddi dysfunction is not known. This study sought to determine
      whether pancreatic sphincter hypertension might explain some of the increased
      risk. PATIENTS AND METHODS: The incidence of pancreatitis was determined from a
      cohort of patients who underwent pancreatic sphincter manometry. Additional data
      collected included: pancreatic and biliary sphincter manometry results, distal
      bile duct diameter, chronic pancreatitis grade by pancreatography, and endoscopic
      treatments. RESULTS: Ten of 32 patients (31%) with pancreatic sphincter
      hypertension developed post-ERCP pancreatitis, compared to one of 33 (3%) with
      normal pancreatic manometry (P = 0.002). Patients with pancreatic sphincter
      hypertension were more likely to undergo endoscopic treatments (88%) compared to
      those with normal manometry (27%) (P = 0.001). The distal bile duct diameter was
      significantly smaller (4.5 +/- 0.5 mm) in patients who developed post-ERCP
      pancreatitis than in those who did not (6.2 +/- 0.3) (P = 0.025). Patients with
      small distal bile duct diameters (< 5 mm) were three times more likely to develop
      post-ERCP pancreatitis than those with larger ducts (relative risk [RR] 3.1, 95%
      confidence interval [CI] 0.9, 10.7). Patients with pancreatic sphincter
      hypertension were ten times more likely to develop post-ERCP pancreatitis than
      those with normal pancreatic manometry (RR 10.3, 95% CI 1.5, 76.0). In patients
      with a small bile duct size, pancreatic sphincter hypertension substantially
      increased the risk compared to those with normal manometry (RR 18.1, 95% CI 1.1,
      287.6). CONCLUSIONS: Pancreatic sphincter hypertension greatly increases the risk
      of post-ERCP pancreatitis in patients undergoing treatment or evaluation, or
      both, for sphincter of Oddi dysfunction.

PMID- 9255528
TI  - Endoscopic sphincterotomy for choledocholithiasis: a prospective single-center
      study on the short-term and long-term treatment results in 483 patients.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy (EST) is the method of
      choice for the treatment of choledocholithiasis. The aim of the present study was
      to assess the impact of various prognostic factors on the short-term and long
      term results of EST. PATIENTS AND METHODS: Data from 483 EST procedures carried
      out due to choledocholithiasis without concomitant neoplasms or hepatic
      cirrhosis, and without subsequent bile duct surgery, were analyzed prospectively.
      The 324 patients (67%) who agreed to take part in the follow-up examinations and
      fulfilled the inclusion criteria for the study were divided into four groups,
      depending on the presence of the gallbladder or cholecystolithiasis prior to EST
      and on the time of diagnosis, and were prospectively followed up by physical
      examination laboratory tests, abdominal ultrasound, and endoscopic retrograde
      cholangiography examinations to evaluate the short-term and long-term outcomes.
      RESULTS: EST was successful in 95.7% of cases. Early complications were noted in
      6.8% of cases. No early complications were seen in the group after
      cholecystectomy with a T-tube present, whereas this rate was highest in the group
      with concurrent choledocholithiasis and cholecystolithiasis (six of 48, 12.5%).
      Recurrent choledocholithiasis was observed in 5.6% of the cases overall. This
      rate was at its lowest in patients with choledocholithiasis alone, and was
      highest in the group with concurrent choledocholithiasis and cholecystolithiasis.
      Among the latter patients, the highest rates of papillary stenosis, chronic
      pancreatitis, and cholangitis were also observed, the latter complication being
      noted only in cases of recurrent common bile duct stones. CONCLUSIONS: EST is a
      relatively safe and effective procedure in the treatment of choledocholithiasis.
      The best prognostic factor is the presence of choledocholithiasis alone.
      Concurrent choledocholithiasis and cholecystolithiasis carry a more adverse
      prognosis, and in these cases cholecystectomy should be considered after EST.

PMID- 9255529
TI  - Suprapapillary fistulosphincterotomy at ERCP: a prospective study.
AB  - BACKGROUND AND STUDY AIMS: The role of the needle knife at endoscopic retrograde
      cholangiopancreatography (ERCP) remains controversial, with conflicting views
      being held on the value and safety of this device. The aim of the present study
      was to assess prospectively the value and safety of suprapapillary
      fistulosphincterotomy (FS) in the endoscopic management of biliary disease.
      PATIENTS AND METHODS: Suprapapillary fistulosphincterotomy was performed when
      biliary cannulation had failed after attempting to opacify the bile duct for 30
      minutes, initially with a standard diagnostic cannula and then by further
      attempts with a tapered cannula. The second indication for suprapapillary
      fistulosphincterotomy was inability to obtain satisfactory cannulation with the
      sphincterotome in patients in whom cholangiopancreatography showed pathology
      requiring endoscopic sphincterotomy. Using this technique, an opening was created
      into the intraduodenal segment of the common bile duct at a point on the vertical
      axis 3-5 mm proximal to the papillary orifice. The opening was then cannulated,
      and extended as required to facilitate clearance of stones or stent insertion.
      RESULTS: Of 531 consecutive patients, 83 (16%) underwent suprapapillary
      fistulosphincterotomy, and biliary cannulation was achieved in 74 of the 83
      (89%). If suprapapillary fistulosphincterotomy had not been used, the diagnostic
      success rate would have fallen from 513 out of 531 (97%) to 451 out of 531 (85%)
      (P = 0.0001); the clearance rate for duct stones would have fallen from 150 out
      of 156 (96%) to 130 out of 156 (83%) (P = 0.0003); and successful stent insertion
      would have fallen from 52 out of 59 (88%) to 38 out of 59 (64%) (P = 0.0044).
      There were no fatalities following suprapapillary fistulosphincterotomy.
      Complications occurred in five of the 83 patients (6%) who underwent
      fistulosphincterotomy, compared with five of the 448 patients (1%) who did not
      undergo the procedure (P = 0.01). CONCLUSIONS: Our results suggest that
      suprapapillary fistulosphincterotomy is a valuable adjunct in the management of
      biliary disease at ERCP, but, in view of the increased risk of complications, it
      should be reserved for patients in whom the index of suspicion for biliary
      disease is high and further endoscopic treatment is likely.

PMID- 9255530
TI  - Photodynamic therapy for the treatment of tumor ingrowth in expandable esophageal
      stents.
AB  - BACKGROUND AND STUDY AIMS: Tumor ingrowth through self-expanding metal stents
      presents a difficult problem for management. The techniques for treating tumor
      ingrowth have not yet been well described, and the optimal endoscopic approach is
      not clear. We have recently used photodynamic therapy (PDT) to treat tumor
      ingrowth through uncovered nitinol mesh stents. PATIENTS AND METHODS: Four
      patients (mean age 73) with obstructive adenocarcinomas of the distal esophagus
      had received self-expanding stents for palliation of their dysphagia. After stent
      placement, tumor ingrowth had caused progressive dysphagia in all of the
      patients; the dysphagia was graded on a scale from 0 (normal) to 4 (inability to
      swallow liquids). All of the patients received PDT treatment. RESULTS: After PDT,
      excellent palliation of the dysphagia was seen in all of the patients, with a
      mean improvement in the dysphagia score of 2.25 and a mean dysphagia-free
      interval of 92 days. There were no major complications. CONCLUSION: The use of
      PDT to treat tumor ingrowth through self-expanding metal esophageal stents is
      effective and safe.

PMID- 9255531
TI  - Enhanced effectiveness of photodynamic therapy with laser light fractionation in
      patients with esophageal cancer.
AB  - BACKGROUND AND STUDY AIMS: The fractionated application of laser light has been
      shown to enhance the effect of photodynamic therapy (PDT) on normal rat colon
      after photosensitization with 5-aminolevulinic acid. In a pilot study, we
      examined whether this modified laser treatment can also enhance the effect of PDT
      in patients with esophageal cancer after sensitization with hematoporphyrins.
      PATIENTS AND METHODS: Six patients (four cases of early esophageal carcinoma and
      two cases of advanced esophageal carcinoma, one of the latter patients having
      tumor overgrowth on a metal stent) were treated in nine sessions. In four
      sessions, laser energy was fractionated to enhance the PDT effect using a
      hematoporphyrin polyester. Irradiation was carried out 48 hours after
      sensitization. The total laser energy of 150 J/cm2 was applied either
      continuously or in fractions, with a single break of five minutes after 75 J/cm2.
      RESULTS: Among the three patients who underwent continuous laser light
      irradiation, one patient experienced a complete remission of two of three
      superficial esophageal cancers. The patient with tumor overgrowth on an implanted
      metal stent showed a partial response, with improvement of dysphagia without
      destruction of the stent, while in another patient with advanced esophageal
      cancer, the dysphagia did not improve after continuous laser treatment.
      Fractionated laser therapy led to complete remission in all three patients with
      early cancers, one of whom had failed to respond to previous treatment with
      continuous PDT. A partial remission was obtained in a fourth patient with a uT2
      cancer who had also shown no remission after continuous PDT treatment. However,
      after fractionated laser therapy, three mild esophageal stenoses occurred, in
      comparison with none after continuous PDT. CONCLUSIONS: Light fractionation
      during PDT improved the effectiveness of the treatment in a small number of
      patients, and increased side effects such as the occurrence of mild esophageal
      stenosis. This modified treatment can be a promising approach in the effort to
      reduce the dose of hematoporphyrins or other sensitizers required, and to avoid
      prolonged skin sensitization or local stenosis.

PMID- 9255532
TI  - Sclerotherapy is out--nearly.

PMID- 9255533
TI  - Is sclerotherapy out?

PMID- 9255534
TI  - Diagnosis and prevention of post-ERCP pancreatitis.

PMID- 9255535
TI  - Complications of endoscopic biliary sphincterotomy: a review.
AB  - Short-term complications of sphincterotomy can vary widely in different
      circumstances, and appear to be related primarily to two factors: the indication
      for the procedure, and the technical skill of the endoscopist. The risk of
      sphincterotomy is highest when it is performed for suspected sphincter of Oddi
      dysfunction, and lowest when it is performed for bile duct stone extraction in
      tandem with laparoscopic cholecystectomy. The endoscopic technique is an
      important factor in complications, and this is in turn related to the case
      volume, and presumably the skill and training of the endoscopist. With the
      exception of cirrhosis and perhaps other specific conditions, the patient's
      general medical condition appears to have little impact on the overall risk of
      sphincterotomy. Complications represent only one facet of negative outcomes in
      attempted sphincterotomy: failure to achieve bile duct access at all, failure of
      completed sphincterotomy to achieve its intended therapeutic response, and its
      long-term sequelae, may be at least as important in determining the overall
      outcome of sphincterotomy.

PMID- 9255536
TI  - Current status and trends in laparoscopic antireflux surgery: results of a
      consensus meeting. The European Study Group for Antireflux Surgery (ESGARS).
AB  - Laparoscopic surgery for gastroesophageal reflux disease has replaced the open
      approach in several institutions, and it is likely to become the "standard" for
      treatment in the near future. Members of five European surgical centers with
      extensive experience in pathophysiological research, diagnostic testing, and
      conventional surgery for esophageal disease met after five years of experience in
      using laparoscopic antireflux surgery, and established a plan to evaluate the
      potential for consensus among the centers involved in the surgical management of
      the disease. The consensus process started with a pathophysiological assessment
      of the reporting requirements for diagnostic workup. To allow a thorough
      appreciation of the surgical techniques used by all the participants, experience
      was exchanged in collaborative operations in an experimental surgical laboratory.
      It was concluded that the pathophysiological background to the disease is
      multifactorial, as many publications have shown in recent years. The group's
      meetings and discussions established a consensus list for the preoperative
      assessment of patients suspected of having gastroesophageal reflux disease, as
      well as a common list of operative techniques for successful antireflux surgery.

PMID- 9255537
TI  - Laparoscopic adrenalectomy: history, indications, and current techniques for a
      minimally invasive approach to adrenal pathology.
AB  - Refinements in the field of laparoscopic general surgery have not only made the
      performance of laparoscopic adrenalectomy technically feasible, but have even
      made it the preferred method of treatment for benign adrenal pathology. The
      advantage of the laparoscopic approach lies in the fact that it allows precise,
      hemostatic dissection of the gland in a minimally invasive fashion. We present
      here the results of published reports of laparoscopic adrenalectomy as well as
      our own experience, and compare these data with reports from open procedures. The
      indications for the surgical removal of the adrenal gland have not changed, and
      include: endocrine active tumors, suspected malignancies, adrenal masses larger
      than 6 cm, and masses that have been followed and observed to be growing.
      Laparoscopic adrenalectomy can be accomplished with one of three approaches:
      anterior, lateral and posterior. Each approach has advantages and limitations,
      and our preferences are discussed. The general techniques are briefly described.
      The findings from many studies show that the blood loss, operative complications,
      hospital stay and recovery period are significantly reduced with the laparoscopic
      approach. Based on our experience with 19 laparoscopic adrenalectomies and a
      review of the current literature, laparoscopic adrenalectomy can be fairly
      described as the current "gold standard" treatment for benign adrenal disease.
      Patients benefit from short hospital stays, lower morbidity, and a more rapid
      recovery. The only question that remains is the appropriateness of laparoscopic
      adrenalectomy in the treatment of adrenal malignancy, and the answer to this will
      depend on the results of long-term outcome studies.

PMID- 9255538
TI  - The value of pancreatoscopy in patients with mucinous ductal ectasia.
AB  - We report here on three cases of mucinous ductal ectasia in which the diagnosis
      was suggested by abdominal computed tomography and finally established by
      duodenoscopy with pancreatoscopy. Duodenoscopic examination of the ampulla of
      Vater demonstrated a patulous papillary orifice and extrusion of viscid mucus.
      Pancreatoscopic examination was carried out in all three patients, and
      characteristic findings such as papillary or villous mucosal projections coated
      with whitish gelatinous mucus were noted. In patients with mucinous ductal
      ectasia in whom the radiographic findings are equivocal, pancreatoscopic
      examination may provide valuable information for the differential diagnosis of
      amorphous filling defects in the main pancreatic duct, and may provide
      information that helps to determine the extent of the pathology and the resection
      margin.

PMID- 9255539
TI  - Endoscopic treatment of gastric outlet obstruction caused by a gallstone
      (Bouveret's syndrome) after extracorporeal shock-wave lithotripsy.
AB  - Two patients with gastric outlet obstruction caused by a gallstone were treated
      by endoscopic lithotripsy. All fragments of significant size were removed orally,
      except for one that was left in the stomach in the first patient. This fragment
      caused a recurrent ileus after initial clinical improvement. The other patient
      remained clinically well after hospital discharge.

PMID- 9255540
TI  - Early detection of recurrent hepatocellular carcinoma by endosonographically
      guided fine-needle aspiration biopsy.
AB  - Fine-needle aspiration guided by endoscopic ultrasonography (EUS) has shown
      promising results in establishing the cytological diagnosis of lesions identified
      during endoscopic ultrasound examinations. We report here on a case of recurrent
      hepatocellular carcinoma diagnosed by EUS-guided biopsy in which curative
      resection was possible as a result of early diagnosis.

PMID- 9255541
TI  - A case of colonic pseudolipomatosis: a rare complication of colonoscopy?
AB  - Mucosal pseudolipomatosis of the colon is a rare complication of colonoscopy. It
      is a benign lesion, and the etiology and pathogenesis of the disorder remain
      controversial. We report here a case of pseudolipomatosis of the colon discovered
      during investigation of rectal bleeding.

PMID- 9255542
TI  - Portal hypertensive colopathy: a recently recognized entity.

PMID- 9255543
TI  - Should we still use button gastrostomy tubes as replacements for percutaneous
      endoscopic gastrostomy tubes?

PMID- 9255544
TI  - Simultaneous endoscopic and radiological examination of the colon.

PMID- 9255545
TI  - Benign gastric ulcer masquerading as a submucosal tumor.

PMID- 9255546
TI  - Tension pneumothorax complicating a perforation of a duodenal ulcer during ERCP
      with endoscopic sphincterotomy.

PMID- 9255547
TI  - Cronkhite--Canada syndrome without colonic polyps.

PMID- 9255548
TI  - A case of phlebosclerotic ischemic colitis: a distinct entity.

PMID- 9255549
TI  - Endosonographic detection of a mucinous adenocarcinoma in an anal fistula.

PMID- 9255550
TI  - Endoscopic magnetic resonance imaging at variable coil orientations.

PMID- 9255551
TI  - Transnasal percutaneous endoscopic gastrostomy.

PMID- 9255552
TI  - Can the expandable esophageal metal Endocoil stent be safely removed?

PMID- 9255553
TI  - Duodenal Endoclip migration after laparoscopic cholecystectomy: report of a case.

PMID- 9255555
TI  - Genetic and environmental factors associated with variation of human xenobiotic
      glucuronidation and sulfation.
AB  - Glucuronidation and sulfation are phase 2 metabolic reactions catalyzed by large
      families of different isoenzymes in man. The textbook view that glucuronidation
      and sulfation lead to the production of harmless conjugates for simple excretion
      is not valid. Biologically active and toxic sulfates and glucuronides are
      produced and leed to adverse drug reactions, including immune hypersensitivity.
      Considerable variation in xenobiotic conjugation is observed as a result of
      altered expression of UDP-glucuronosyltransferases (UGTs) and sulfotransferases
      (STs). Recent cloning and expression of human cDNA encoding UGTs and STs has
      facilitated characterization of isoform substrate specificity, which has been
      further validated using specific antibodies and human tissue fractions. The
      availability of cloned/expressed human enzymes and specific antibodies has
      enabled the investigation of xenobiotic induction and metabolic disruption
      leeding to adverse responses. Genetic polymorphisms of glucuronidation and
      sulfation are known to exist although the characterization and assessment of the
      importance of these variations are hampered by appropriate ethical studies in men
      with suitable safe model compounds. Genetic analysis has allowed molecular
      identification of defects in well-known hyperbilirubinemias. However, full
      characterization of the specific functional roles of human UGTs and STs requires
      rigorous kinetic and molecular analyses of the role of each enzyme in vivo
      through the use of specific antibodies and inhibitors. This will leed to the
      better prediction of variation of xenobiotic glucuronidation and sulfation in
      man.

PMID- 9255557
TI  - Combinations of susceptible genotypes and individual responses to toxicants.
AB  - The variation in individual responses to exogenous agents has been shown to be
      exceptionally wide. It is because of this large diversity of responsiveness that
      risk factors to environmentally induced diseases have been difficult to pinpoint,
      particularly at low exposure levels. Opportunities now exist for studies of host
      factors in environmentally induced cancer or other diseases in which an
      environmental component can be presumed. Many of the studies have shown an
      elevated disease proneness for individuals carrying the potential at-risk alleles
      of metabolic genes, but a number of controversial results have also been
      reported. One possible explanation for the divergent findings is lack of
      knowledge of the other potentially relevant genotypes for a given exposure. This
      paper gives an overview of the published data on combinations of metabolic
      genotypes in relation to individual susceptibility to environmental toxicants.

PMID- 9255558
TI  - Genetic polymorphism of cytochrome P450 as a biomarker of susceptibility to
      environmental toxicity.
AB  - Cytochrome P450 (CYP) enzymes are responsible for the metabolism of numerous
      xenobiotics and endogenous compounds, including the metabolic activation of most
      environmental toxic chemicals and carcinogens. Both metabolic and genetic
      polymorphisms have been identified for human CYP enzymes. The association of CYP
      genetic polymorphism and human cancer risk, and susceptibility to environmental
      hazards, have received increasing attention. This article briefly reviews the
      approaches and methods currently used in CYP genetic polymorphism studies. In
      addition, the current status and perspectives of using CYP genetic polymorphism
      as a biomarker of individual susceptibility to cancer and environmental toxicity
      are discussed.

PMID- 9255556
TI  - Interaction between dose and susceptibility to environmental cancer: a short
      review.
AB  - Increased risk of environmentally induced cancer is associated with various types
      of exposures and host factors, including differences in carcinogen metabolism.
      Since many carcinogenic compounds require metabolic activation to enable them to
      react with cellular macromolecules, individual features of carcinogen metabolism
      may play an essential role in the development of environmental cancer. In this
      context, cigarette smoking has often been the main type of carcinogenic exposure
      examined in human studies. Increasing attention has recently been paid to the
      dose level at which individual susceptibility may be observed. Present studies on
      increased risk of smoking-related lung cancer associated with phenotypic or
      genotypic variation of the genes encoding for CYP1A1 or CYP2D6 enzymes are
      summarized. Similarly, higher risks of lung or bladder cancer seen at various
      levels of smoking in association with polymorphism of the glutathione S
      transferase gene GSTM1 or NAT1 and NAT2 genes involved in N-acetylation are
      reviewed. Finally, the influence of CYP2E1, GSTM1, or the combined at-risk
      genotype on the risk of hepatocellular carcinoma in smokers is briefly discussed.

PMID- 9255554
TI  - 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation
      of Chemicals: susceptibility to environmental hazards.
AB  - The 12th meeting of the Scientific Group on Methodologies for the Safety
      Evaluation of Chemicals (SGOMSEC) considered the topic of methodologies for
      determining human and ecosystem susceptibility to environmental hazards. The
      report prepared at the meeting describes measurement of susceptibility through
      the use of biological markers of exposure, biological markers of effect, and
      biomarkers directly indicative of susceptibility of humans or of ecosystems. The
      utility and validity of these biological markers for the study of susceptibility
      are evaluated, as are opportunities for developing newer approaches for the study
      of humans or of ecosystems. For the first time a SGOMSEC workshop also formally
      considered the issue of ethics in relation to methodology, an issue of particular
      concern for studies of susceptibility.

PMID- 9255559
TI  - Acetylation as an indicator of risk.
AB  - Aromatic amine acetylation has been recognized for many years as an important
      metabolic polymorphism in humans because of its relationship to disease. This
      system serves as a model in risk assessment because of its role in drug and
      carcinogen activation and detoxification and because of the case with which it is
      measured. However, possible interactions of NAT1-NAT2 phenotypes or genotypes
      illustrate the complexity of xenobiotic metabolism pathways. Moreover, the use of
      such information for risk assessment is further complicated by the association of
      the rapid phenotype with increased risk in colon cancer and the slow phenotype
      with increased risk in urinary bladder cancer. Before this biomarker can be
      effectively utilized as a significant predictor of individual risk, it will be
      necessary to identify specific sources of aromatic amine exposure and to
      characterize further the substrate specificity of NAT1 and NAT2 in relation to
      the multiplicity of enzyme variants occurring in human populations.

PMID- 9255560
TI  - Metabolic activation of toxins: tissue-specific expression and metabolism in
      target organs.
AB  - Cytochrome P450 (CYP) enzymes catalyze the generation of reactive species capable
      of binding with cellular macromolecules, leading to acute and delayed toxicity.
      Since individual CYP forms differ markedly in their substrate preferences and
      regulation, the expression profiles of CYP in various cell types are important
      determinants in tissue-specific toxicity. The highest concentrations of most
      forms of CYP are found in liver, but they are also present in many extrahepatic
      organs. Liver is also a target organ in which CYP-mediated activation and toxic
      outcome have been most convincingly linked. Prime examples are paracetamol
      induced hepatotoxicity and aflatoxin B1-associated hepatic cancer. In contrast to
      liver, most extrahepatic tissues are composed of multiple call types, which make
      experimental approaches difficult. Also the low abundance of individual forms is
      a challenge in the study of extrahepatic CYP-related toxicity. Recent years have
      witnessed the emergence of molecular biological techniques, e.g., reverse
      transcriptase-polymerase chain reactions, which facilitate the study of low
      abundant CYP forms in human tissues. Nevertheless, in the end we need definite
      information on the expression of activity, and for this purpose enzyme-specific
      substrates, reactions, and inhibitors and other methods to detect proteins and
      associated activities are needed. In humans, it is important to measure
      activities of specific enzymes in vivo. For this purpose, two approaches are
      currently available. Metabolism and/or elimination of enzyme-specific drugs can
      be employed. In cases in which genetic background determines the presence or
      absence of a specific enzyme, phenotyping and genotyping tests can be devised,
      e.g., for CYP2D6 (debrisoquine hydroxylation) polymorphism.

PMID- 9255561
TI  - DNA mismatch repair gene mutations in human cancer.
AB  - A new pathogenetic mechanism leading to cancer has been delineated in the past 3
      years when human homologues of DNA mismatch repair (MMR) genes have been
      identified and shown to be involved in various types of cancer. Germline
      mutations of MMR genes cause susceptibility to a hereditary form of colon cancer,
      hereditary nonpolyposis colon cancer (HNPCC), which represents one of the most
      common syndromes associated with cancer predisposition in man. Tumors from HNPCC
      patients are hypermutable and show length variation at short tandem repeat
      sequences, a phenomenon referred to as microsatellite instability or replication
      errors. A similar abnormality is found in a proportion of sporadic tumors of the
      colorectum as well as a variety of other organs; acquired mutations in MMR genes
      or other endogenous or exogenous causes may underlie these cases. Genetic and
      biochemical characterization of the functions of normal and mutated MMR genes
      elucidates mechanisms of cancer development and provides tools for diagnostic
      applications.

PMID- 9255562
TI  - Mini- and microsatellites.
AB  - While the faithful transmission of genetic information requires a fidelity and
      stability of DNA that is involved in translation into proteins, it has become
      evident that a large part of noncoding DNA is organized in repeated sequences,
      which often exhibit a pronounced instability and dynamics. This applies both to
      longer repeated sequences, minisatellites (about 10-100 base pairs), and
      microsatellites (mostly 2-4 base pairs). Although these satellite DNAs are
      abundantly distributed in all kinds of organisms, no clear function has been
      discerned for them. However, extension of trinucleotide microsatellite sequences
      has been associated with several severe human disorders, such as Fragile X
      syndrome and Huntington's disease. Rare alleles of a minisatellite sequence have
      been reported to be associated with the ras oncogene leading to an increased risk
      for several human cancers. A dynamic behavior of repeated DNA sequences also
      applies to telomeres, constituting the ends of the chromosomes. Repeated DNA
      sequences protect the chromosome ends from losing coding sequences at cell
      divisions. The telomeres are maintained by the enzyme telomerase. Somatic cells,
      however, lose telomerase function and gradually die. Cancer cells have activated
      telomerase and therefore they acquire immortality.

PMID- 9255564
TI  - Biomarkers of human exposure to pesticides.
AB  - For centuries, several hundred pesticides have been used to control insects.
      These pesticides differ greatly in their mode of action, uptake by the body,
      metabolism, elimination from the body, and toxicity to humans. Potential exposure
      from the environment can be estimated by environmental monitoring. Actual
      exposure (uptake) is measured by the biological monitoring of human tissues and
      body fluids. Biomarkers are used to detect the effects of pesticides before
      adverse clinical health effects occur. Pesticides and their metabolites are
      measured in biological samples, serum, fat, urine, blood, or breast milk by the
      usual analytical techniques. Biochemical responses to environmental chemicals
      provide a measure of toxic effect. A widely used biochemical biomarker,
      cholinesterase depression, measures exposure to organophosphorus insecticides.
      Techniques that measure DNA damage (e.g., detection of DNA adducts) provide a
      powerful tool in measuring environmental effects. Adducts to hemoglobin have been
      detected with several pesticides. Determination of chromosomal aberration rates
      in cultured lymphocytes is an established method of monitoring populations
      occupationally or environmentally exposed to known or suspected mutagenic
      carcinogenic agents. There are several studies on the cytogenetic effects of work
      with pesticide formulations. The majority of these studies report increases in
      the frequency of chromosomal aberrations and/or sister chromatid exchanges among
      the exposed workers. Biomarkers will have a major impact on the study of
      environmental risk factors. The basic aim of scientists exploring these issues is
      to determine the nature and consequences of genetic change or variation, with the
      ultimate purpose of predicting or preventing disease.

PMID- 9255563
TI  - The role of human glutathione transferases and epoxide hydrolases in the
      metabolism of xenobiotics.
AB  - Human glutathione transferases (GSTs) are a multigene family of enzymes that are
      involved in the metabolism of a wide range of electrophilic compounds of both
      exogenous and endogenous origin. GSTs are generally recognized as detoxifying
      enzymes by catalyzing the conjugation of these compounds with glutathione, but
      they may also be involved in activation of some carcinogens. The memmalian GSTs
      can be differentiated into four classes of cytosolic enzymes and two membrane
      bound enzymes. Human epoxide hydrolases (EHs) catalyze the addition of water to
      epoxides to form the corresponding dihydrodiol. The enzymatic hydration is
      essentially irreversible and produces mainly metabolites of lower reactivity that
      can be conjugated and excreted. The reaction of EHs is therefore generally
      regarded as detoxifying. The mammalian EHs can be distinguished by their physical
      and enzymatic properties. Microsomal EH (mEH) exhibits a broad substrate
      specificity, while the soluble EH (sEH) is an enzyme with a "complementary"
      substrate specificity to mEH. Cholesterol EH and leukotriene A4 hydrolase are two
      EHs with very limited substrate specificity. The activities of either GSTs or EHs
      expressed in vivo exhibit a relatively large interindividual variation, which
      might be explained by induction, inhibition, or genetic factors. These variations
      in levels or activities of individual isoenzymes are of importance with respect
      to an individual's susceptibility to genotoxic effects. This article gives a
      general overview of GSTs and EHs, discussing the modulation of activities,
      determination of these enzymes ex vivo, and the polymorphic expression of some
      isoenzymes.

PMID- 9255565
TI  - Biomarkers of gene expression: growth factors and oncoproteins.
AB  - This article reviews the literature on the application of methods for the
      detection of growth factors, oncogene proteins, and tumor-suppressor gene
      proteins in the blood of humans with cancer or who are at risk for the
      development of cancer. The research summarized here suggests that many of these
      biomarker assays can be used to distinguish between diseased and nondiseased
      states and in some instances may be able to predict susceptibility for future
      disease. Thus, these biomarkers could be valuable tools for monitoring at-risk
      populations for purposes of disease prevention and control.

PMID- 9255567
TI  - DNA adducts and mutations in occupational and environmental biomonitoring.
AB  - The methods applied for DNA adduct determination in humans have become more
      reliable. Yet there is a need to characterize the adducts studied better and when
      possible, to identify them with the help of the available standard compounds. Use
      of standard compounds also allows quantification of adduct levels. There is a
      lack of knowledge on the adduct levels and their half-lives in target and
      surrogate tissues. Most adduct studies have been carried out on occupational
      populations exposed to complex mixtures. White blood cells have been the most
      common source of DNA. Other exposures and tissues should be a subject of study.
      Notably, dietary exposures have been largely neglected. Biomonitoring of
      mutations is a relatively new field and a few exposures have so far been
      investigated. The results have been promising but logistics of the studies have
      to be improved to make large field studies possible. Future biomonitoring studies
      should make an effort to combine many end points, with emphasis on adducts,
      mutations, and constitutional metabolic factors.

PMID- 9255566
TI  - Factors influencing susceptibility to metals.
AB  - Although the long-neglected field of human susceptibility to environmental
      toxicants is currently receiving renewed attention, there is only scant
      literature on factors influencing susceptibility to heavy metals. Genetic factors
      may influence the availability of sulfhydryl-containing compounds such as
      glutathione and metallothionein, which modify the distribution and toxicity of
      certain metals. Age and gender play a role in modifying uptake and distribution,
      although the mechanisms are often obscure. Concurrent exposure to divalent
      cations may enhance or reduce the toxicity of certain metals through competition
      for receptor-mediated transport or targets. Increasing use of biomarkers of
      exposure should greatly increase our understanding of the underlying distribution
      of susceptibility to various environmental agents.

PMID- 9255569
TI  - Ethical, social, and legal issues surrounding studies of susceptible populations
      and individuals.
AB  - Calls for professional accountability have resulted in the development of ethics
      guidelines by numerous specialty and subspecialty groups of scientists. Indeed,
      guidelines among some health professions now address vulnerable and dependent
      groups: but these are silent on issues related to biomarkers. In parallel,
      attention has been drawn to human rights concerns associated with attempts to
      detect hypersusceptible workers, especially in democratic countries. Despite
      this, concern for vulnerable populations grows as advances in biomarker
      technology make the identification of genetic predisposition and susceptibility
      markers of both exposure and outcome more attainable. In this article, the
      principles derived from the ethical theory of utilitarianism provide the basis
      for principle-based ethical analysis. In addition, the four principles of
      biomedical ethics--respect for autonomy, beneficence, nonmaleficence, and social
      justice--are considered for biomarker studies. The need for a context in which
      ethical analysis is conducted and from which prevailing social values are shown
      to drive decisions of an ethical nature is emphasized; these include statutory
      regulation and law. Because biomarker studies can result in more harm than good,
      special precautions to inform research participants prior to any involvement in
      the use of biomarkers are needed. In addition, safeguards to maintain the privacy
      of data derived from biomarker studies must be developed and implemented prior to
      the application of these new technologies. Guidelines must be expanded to
      incorporate ethical, social, and legal considerations surrounding the
      introduction of new technologies for studying susceptible populations and
      individuals who may be vulnerable to environmental exposures.

PMID- 9255568
TI  - Cytogenetic markers of susceptibility: influence of polymorphic carcinogen
      metabolizing enzymes.
AB  - Polymorphisms of xenobiotic-metabolizing enzymes, responsible for individual
      differences in metabolic activation and detoxification reactions, may profoundly
      modulate the effects of chemical carcinogens. In the case of genotoxic
      carcinogens, differences in biological effects due to genetic polymorphisms can
      be evaluated by cytogenetic methods such as the analysis of chromosomal
      aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and
      changes in chromosome number. These techniques can be applied to any exposure
      known to induce such alterations, without additional method development for each
      exposing agent. The influence of polymorphic genes on the cytogenetic effects of
      a carcinogen can quickly be tested in vitro using metabolically competent cells
      collected from donors representing different genotypes or phenotypes. For
      instance, erythrocytes from individuals positive for glutathione S-transferase T1
      (GSTT1) express GSTT1, whereas GSTT1-null donors, having a homozygous deletion of
      the GSTT1 gene, completely lack this detoxification enzyme. This deficiency
      results in highly increased sensitivity to SCE induction in whole-blood
      lymphocyte cultures by 1,2:3,4-diepoxybutane, a reactive metabolite of 1,3
      butadiene. The same cytogenetic techniques can also be applied as effect
      biomarkers in studies of human populations exposed to genotoxic carcinogens. For
      example, elevated rates of chromosome damage have been detected among smokers
      lacking glutathione S-transferase M1 (GSTM1-null genotype), and the baseline
      level of SCEs seems to be increased in GSTT1-null individuals. Information
      obtained from cytogenetic studies of genetic polymorphisms can be used, for
      example, to recognize the genotoxically relevant substrates of the polymorphic
      enzymes, to identify genotypes that are susceptible to these genotoxins, to
      improve in vitro genotoxicity tests utilizing human cells, to increase the
      sensitivity of cytogenetic endpoints as biomarkers of genotoxic effects in
      humans, and to direct mechanistic studies and cancer epidemiology.

PMID- 9255570
TI  - Methods for and approaches to evaluating susceptibility of ecological systems to
      hazardous chemicals.
AB  - Differences in genetic susceptibility to hazardous chemicals affect individuals
      of both human and nonhuman populations. In both cases, differences in response to
      chemicals or general ill health result as a function of these differences in
      genetic susceptibility. However, ecological systems are a compilation of hundreds
      or even thousands of different species, resulting in structural and functional
      characteristics that are themselves affected by differences in susceptibility.
      Although individual and population differences in susceptibility to hazardous
      chemicals underlie effects at the community and the ecosystem level, they do not
      account for all differences. I propose a two-tiered approach to evaluating
      susceptibility to ecological systems: a general susceptibility as a function of
      ecosystem type (based on structure and function of that system) and a
      differential in susceptibility within broad ecosystem types as a function of
      biotic and abiotic factors. In terrestrial ecosystems, the two factors that most
      affect overall susceptibility are species diversity and hydrology; evaluation of
      the effects of hazardous chemicals involves measuring species diversity and water
      movement. This same methodological approach can be applied to aquatic ecosystems
      and to highly altered ecosystems such as agriculture, forestry, fisheries, and
      urbanization.

PMID- 9255571
TI  - Genetic susceptibility in ecosystems: the challenge for ecotoxicology.
AB  - Environmental management is inevitably complicated by the large variation in
      susceptibility to chemical toxicity exhibited by the living components of
      ecosystems, a significant proportion of which is determined by genetic factors.
      This paper examines the concept of genetic susceptibility in ecosystems and
      suggests the existence of two distinct forms reflecting genetic changes at the
      level of the individual and at the level of population and community. The
      influence of genetic susceptibility on exposure-response curves is discussed and
      the consequent accuracy of data used for toxicity test-based risk assessments
      examined. The paper concludes by describing a possible biomarker-based approach
      to future studies of susceptibility in ecosystems, suggesting the use of modern
      molecular genetic methods.

PMID- 9255572
TI  - A new type of hazardous chemical: the chemosensitizers of multixenobiotic
      resistance.
AB  - The purpose of this overview is to introduce the property of a new class of
      hazardous chemicals-the inhibitors of multixenobiotic resistance (MXR) in aquatic
      organisms, referred to as chemosensitizers. Aquatic organisms possess MXR, a
      mechanism similar to the well-known P-glycoprotein extrusion pump in multidrug
      resistant (MDR) tumor cells. MXR in aquatic organism moves from cells and
      organisms both endogenous chemicals and xenobiotics, including also some man-made
      chemicals. MXR in aquatic organisms represents a general biological first-line
      defense mechanism for protection against environmental toxins. Many chemical
      agents, the chemosensitizers, may after the function of this fragile mechanism.
      It is this new, MXR-inhibiting property, unrecognized as yet, that classifies
      these chemicals among top-rank hazardous water pollutants. The knowledge that the
      presence of one xenobiotic may block the pumping out of other xenobiotic(s), and
      hence accelerate their accumulation, may have important implications on
      environmental parameters like exposure, uptake, bioaccumulation, and toxicity. In
      this overview we present the evidence for the expression of MXR-phenotype in
      aquatic organisms, the demonstration of toxic consequences caused by MXR
      inhibitors, and the description of methods for measurement of concentration of
      MXR inhibitors in environmental samples.

PMID- 9255575
TI  - Epidemiologic studies of ionizing radiation and cancer: past successes and future
      challenges.
AB  - The health effects of radiation have been a focus for research since early in the
      20th century. As the century ends, extensive experimental and epidemiologic
      evidence has been accumulated that addresses the adverse consequences of
      radiation exposure; epidemiologic studies of radiation-exposed groups from the
      general population and specific occupational groups provide quantitative
      estimates of the cancer risks associated with exposure. This report provides a
      perspective on the extensive epidemiologic evidence on the health effects of
      ionizing radiation and on likely needs for further epidemiologic research on
      radiation and health. Epidemiologic studies have proved informative on the
      quantitative risks of radiation-caused cancer but we now face the challenges of
      more precisely characterizing risks at lower levels of exposure and also of
      assessing modifiers of the risks, including dose rate, genetic susceptibility,
      and other environmental exposures. This report considers investigative
      approaches, such as pooled analysis of multiple data sets, that can be used to
      address these complex questions and the limitations of these approaches for
      addressing societal concerns about the risks of radiation exposure.

PMID- 9255573
TI  - The causes and prevention of cancer: gaining perspective.
AB  - Epidemiological studies have identified several factors that are likely to have a
      major effect on reducing rates of cancer: reduction of smoking, increased
      consumption of fruits and vegetables, and control of infections. Other factors
      include avoidance of intense sun exposure, increased physical activity, and
      reduced consumption of alcohol and possibly red meat. Risks of many types of
      cancer can already be reduced, and the potential for further reductions is great.
      In the United States, cancer death rates for all cancers combined are decreasing,
      if lung cancer (90% of which is due to smoking), is excluded from the analysis.
      We review the research on causes of cancer and show why much cancer is
      preventable. The idea that traces of synthetic chemicals, such as DDT, are major
      contributors to human cancer is not supported by the evidence, yet public concern
      and resource allocation for reduction of chemical pollution are very high, in
      part because standard risk assessment uses linear extrapolation from limited data
      in high-dose animal cancer tests. These tests are done at the maximum tolerated
      dose (MTD) and are typically misinterpreted to mean that low doses of synthetic
      chemicals and industrial pollutants are relevant to human cancer. About half the
      chemicals tested, whether synthetic or natural, are carcinogenic to rodents at
      such high doses. Almost all chemicals in the human diet are natural. For example,
      99.99% of the pesticides we eat are naturally present in plants to ward off
      insects and other predators. Half of the natural pesticides that have been tested
      at the MTD are rodent carcinogens. Cooking food produces large numbers of natural
      dietary chemicals. Roasted coffee, for example, contains more than 1000
      chemicals: of 27 tested, 19 are rodent carcinogens. Increasing evidence supports
      the idea that the high frequency of positive results in rodent bioassays is due
      to testing at the MTD, which frequently can cause chronic cell killing and
      consequent cell replacement-a risk factor for cancer that can be limited to high
      doses. Because default risk assessments use linear extrapolation, which ignores
      effects of the high dose itself, low-dose risks are often exaggerated.

PMID- 9255574
TI  - Cigarette smoke radicals and the role of free radicals in chemical
      carcinogenicity.
AB  - This article consists of two parts: a brief overview of the ways in which free
      radicals can be involved in chemical carcinogenesis, and a review of cigarette
      smoke chemistry. Carcinogenesis is generally agreed to involve at least three
      stages: initiation, promotion, and progression. It is suggested that radicals
      sometimes are involved in the initiation step, either in the oxidative activation
      of a procarcinogen (such as benzo[a]pyrene) to its carcinogenic form or in the
      binding of the carcinogenic species to DNA, or both. The fraction of initiation
      events that involve radicals, as opposed to two-electron steps, is not known, but
      radicals probably are involved in a substantial number, although probably not a
      majority, of cancer initiation reactions. Promotion always involves radicals, at
      least to some extent. Progression probably does not normally involve radicals.
      The second part of this article reviews the molecular mechanisms involved in
      cigarette-induced tumors, particularly by aqueous cigarette tar (ACT) extracts
      and by a model of these solutions, aged solutions of catechol. ACT solutions as
      well as aged solutions of catechol contain a quinone-hydroquinone-semiquinone
      system that can reduce oxygen to produce superoxide and hence hydrogen peroxide
      and the hydroxyl radical. Both the cigarette tar radical and the catechol-derived
      radical can penetrate viable cells, bind to DNA, and cause nicks.

PMID- 9255577
TI  - Ethnic differences in cancer incidence: a marker for inherited susceptibility?
AB  - Cancer incidence varies markedly by ethnicity and geographic location. Ethnic
      variation in cancer occurrence has traditionally been ascribed to differences in
      social, cultural, economic, and physical environments. However, this
      interpretation of the epidemiologic evidence may need to be revised as a result
      of new biological evidence and theories of carcinogenesis. Carcinogenesis is now
      recognized to be a multistep process during which mutations or heritable changes
      in expression occur in genes involved in cellular growth control and genome
      stability. Inherited cancer susceptibility may be a stronger determinant of
      ethnic differences in cancer incidence than is currently appreciated. To examine
      the potential role of inherited susceptibility, the theoretical contribution of
      inherited susceptibility to ethnic differences in rates in considered using a
      simple probability model. Germline mutations in tumor suppressor genes BRCA1 and
      p53 are used to illustrate the magnitude of the ethnic differences for breast
      cancer that might arise from differences in inherited susceptibility. Our simple
      model suggests that ethnic differences in cancer occurrence can result from
      differences in genetic susceptibility. However, the magnitude of ethnic relative
      risk is likely to more strongly reflect differences in the distribution of
      susceptibility genotypes between groups than the magnitude of the disease risk
      associated with the genotypes. For many scenarios, the ethnic relative risk
      arising from differences in susceptibility may be bounded by the ratio of the
      proportion of susceptible individuals in each group.

PMID- 9255576
TI  - Breast cancer risk and environmental exposures.
AB  - Although environmental contaminants have potential to affect breast cancer risk,
      explicit environmental links to this disease are limited. The most well-defined
      environmental risk factors are radiation exposure and alcohol ingestion. Diet is
      clearly related to the increased incidence of breast cancer in developed
      countries, but its precise role is not yet established. Recent studies have
      implicated exposure to organochlorines including DDT as a risk factor for breast
      cancer in the United States, Finland, Mexico, and Canada. Other investigations
      have discovered associations between breast cancer risk and exposures to chemical
      emissions and some occupational exposures. Several points must be considered in
      evaluating the relationship of environmental exposure to breast cancer. Among
      these considerations are the mechanism of tumorigenesis, timing of environmental
      exposure, and genetic modulation of exposure. Epidemiologic and ecologic
      investigations must take into account the very complex etiology of breast cancer
      and the knowledge that tumorigenesis can arise from different mechanisms. Thus
      crucial exposures as well as reproductive events related to breast cancer may
      occur years before a tumor is evident. Moreover, environmental contaminants may
      alter reproductive development, directly or indirectly, and thereby effect the
      course of tumorigenesis. Such alterations include change in gender, change in
      onset of puberty, and inhibition or promotion of tumor formation. Timing of
      exposure is therefore important with respect to mechanism and susceptibility.
      Finally, genetic polymorphisms exist in genes that govern capacity to metabolize
      environmental contaminants. Higher risk may occur among persons whose enzymes
      either are more active in the production of procarcinogens or fail to detoxify
      carcinogenic intermediates formed from chemicals in the environment.

PMID- 9255578
TI  - Alterations in the K-ras and p53 genes in rat lung tumors.
AB  - Activation of the K-ras protooncogene and inactivation of the p53 tumor
      suppressor gene are events common to many types of human cancers. Molecular
      epidemiology studies have associated mutational profiles in these genes with
      specific exposures. The purpose of this paper is to review investigations that
      have examined the role of the K-ras and p53 genes in lung tumors induced in the
      F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K
      ras and p53 genes, if present in rat lung tumors, would help to define some of
      the molecular mechanisms underlying cancer induction by various environmental
      agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by
      tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK),
      beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These
      agents were chosen because the tumors they produced could arise via different
      types of DNA damage. Mutation of the K-ras gene was determined by approaches that
      included DNA transfection, direct sequencing, mismatch hybridization, and
      restriction fragment length polymorphism analysis. The frequency for mutation of
      the K-ras gene was exposure dependent. Only two agents, TNM and plutonium, led to
      mutation frequencies of > 10%. In both cases, the transition mutations formed
      could have been derived from deamination of cytosine. The identification of non
      ras transforming genes in rat lung tumors induced by mutagenic and nonmutagenic
      exposures such as NNK and beryllium would help define some of the mechanisms
      underlying cancer induction by different types of DNA damage. Alteration in the
      p53 gene was assessed by immunohistochemical analysis for p53 protein and single
      strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93
      adenocarcinomas examined was immunoreactive toward the anti-p53 antibody CM1. In
      contrast, 14 to 71 squamous cell carcinomas exhibited nuclear p53
      immunoreactivity with no correlation to type of exposure. However, SSCP analysis
      only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive,
      suggesting that protein stabilization did not stem from mutations within the p53
      gene. Thus, the p53 gene does not appear to be involved in the genesis of most
      rat lung tumors.

PMID- 9255580
TI  - DNA damage-inducible genes as biomarkers for exposures to environmental agents.
AB  - A biodosimetric approach to determine alpha-particle dose to the respiratory
      tract epithelium from known exposures to radon has been developed in the rat.
      Cytotoxicity assays have been used to obtain dose-conversion factors for
      cumulative exposures typical of those encountered by underground uranium miners.
      However, this approach is not sensitive enough to derive dose-conversion factors
      for indoor radon exposures. The expression of DNA damage-inducible genes is being
      investigated as a biomarker of exposure to radon progeny. Exposure of cultures of
      A549 cells to alpha particles resulted in an increase in the protein levels of
      the DNA damage-inducible genes, p53, Cip1, and Gadd45. These protein changes were
      associated with a transient arrest of cells passing through the cell cycle. This
      arrest was typified by an increase in the number of cells in the G1 and G2 phases
      and a decrease in the number of cells in the S phase. The effect of inhaled alpha
      particles (radon progeny) in rats was examined in the epithelial cells of the
      lateral well of the anterior nasal cavity. Exposures to radon progeny resulted in
      a significant increase in the number of cells in the G1 phase and a decrease in
      the number of cells in the S phase. These cell-cycle changes were concomitant
      with an increase in the number of cells containing DNA strand breaks. These
      results suggest a commonality between cell-cycle events in vitro and in vivo
      following exposure to ionizing radiation. In addition to ionizing radiation, A549
      cells were exposed to 4-nitroquinoline-1-oxide, methyl methanesulphonate,
      crocidolite asbestos, and glass microfiber. These studies showed that physical
      and chemical agents induce different expression patterns of p53, Cip1, and
      Gadd153 proteins and they could be used to discriminate between toxic and
      nontoxic materials such as asbestos and glass microfiber. The measurement of gene
      expression in A549 cells may provide a means to identify a broad spectrum of
      physical and chemical toxicants encountered in the environment.

PMID- 9255579
TI  - DNA adducts as exposure biomarkers and indicators of cancer risk.
AB  - Quantitation of DNA adducts in human tissues has been achieved with highly
      sensitive techniques based on adduct radiolabeling, antisera specific for DNA
      adducts or modified DNA, and/or adduct structural characterization using chemical
      instrumentation. Combinations of these approaches now promise to elucidate
      specific adduct structures and provide detection limits in the range of 1
      adduct/10(9) nucleotides. Documentation of human exposure and biologically
      effective dose (i.e., chemical bound to DNA) has been achieved for a wide variety
      of chemical carcinogens, including polycyclic aromatic hydrocarbons (PAHs),
      aromatic amines, heterocyclic amines, aflatoxins, nitrosamines, cancer
      chemotherapeutic agents, styrene, and malondialdehyde. Due to difficulties in
      exposure documentation, dosimetry has not been precise with most environmental
      and occupational exposures, even though increases in human blood cell DNA adduct
      levels may correlate approximately with dose. Perhaps more significant are
      observations that lowering exposure results in decreasing DNA adduct levels. DNA
      adduct dosimetry for environmental agents has been achieved with dietary
      contaminants. For example, blood cell polycyclic aromatic hydrocarbon-DNA adduct
      levels were shown to correlate with frequency of charbroiled meat consumption in
      California firefighters. In addition, in China urinary excretion of the aflatoxin
      B1-N7-guanine (AFB1-N7-G) adduct was shown to increase linearly with the
      aflatoxin content of ingested food. Assessment of DNA adduct formation as an
      indicator of human cancer risk requires a prospective nested case-control study
      design. This has been achieved in one investigation of hepatocellular carcinoma
      and urinary aflatoxin adducts using subjects followed by a Shanghai liver cancer
      registry. Individuals who excreted the AFB1-N7-G adduct had a 9.1-fold adjusted
      increased relative risk of hepatocellular carcinoma compared to individuals with
      no adducts. Future advances in this field will be dependent on chemical
      characterization of specific DNA adducts formed in human tissues, more-precise
      molecular dosimetry, efforts to correlate DNA adducts with cancer risk, and
      elucidation of opportunities to reduce human DNA adduct levels.

PMID- 9255582
TI  - Epidemiology of ultraviolet-DNA repair capacity and human cancer.
AB  - The following conclusions are derived from an epidemiological study. Reduced
      repair of ultraviolet (UV)-induced DNA damage contributes directly to basal cell
      carcinoma (BCC) in individuals with prior sunlight overexposure. A family history
      of BCC is a predictor of low DNA repair. Repair of UV-damaged DNA declines at a
      fixed rate of approximately 1% per annum in noncancerous controls. The DNA repair
      differences between young BCC cases and their controls disappear as they age.
      Hence, BCC, in terms of DNA repair, is a premature aging disease. The persistence
      of photochemical damage because of reduced repair results in point mutations in
      the p53 gene and allelic loss of the nevoid BCC gene (Gorlin's syndrome) located
      on chromosome 9q. The fact that environmental vulnerability is gender oriented
      implicates hormones in regulating DNA repair. Xeroderma pigmentosum appears to be
      a valid paradigm for the role of DNA repair in BCC in the general population.

PMID- 9255581
TI  - Polymorphisms of H-ras-1 and p53 in breast cancer and lung cancer: a meta
      analysis.
AB  - Certain polymorphic variants of H-ras-1 and p53 have been investigated for an
      association between inheritance and cancer risk. The results of a metaanalysis,
      which reviews studies of H-ras-1 rare alleles and p53 codon 72 allelic variants
      in breast and lung cancer, are presented. The data constituted evidence for
      elevated risk of both breast and lung cancer with inheritance of rare H-ras-1
      alleles. Calculated population attributable risks are 0.092 and 0.037 for breast
      and lung cancer, respectively. The frequency of the rare H-ras-1 alleles was
      observed to be greater in African Americans than in Caucasians, and a specific
      allele (A3.5) that is common in African Americans was found only at low frequency
      in Caucasians. For p53 a consensus has yet to be reached. Lung cancer studies
      conducted in Caucasian and African-American populations have found no evidence of
      risk associated with the proline variant of codon 72. Two similar studies
      conducted in Japanese populations suggested an association between p53 genotype
      distribution and lung cancer risk. However, one implicates the proline allele but
      the other implicates the arginine allele. The frequency of the proline variant is
      significantly dependent on race. Frequencies have been reported for control
      populations of Japanese (0.347 and 0.401), Caucasian (0.295, 0.284, and 0.214),
      African American (0.628 and 0.527), and Mexican American (0.263).

PMID- 9255583
TI  - Regulation of eukaryotic abasic endonucleases and their role in genetic
      stability.
AB  - Abasic (AP) sites in DNA arise from spontaneous reactions or the action of DNA
      glycosylases and represent a loss of genetic information. The AP sites can be
      mutagenic or cytotoxic, and their repair is initiated by class II AP
      endonucleases, which incise immediately 5' to AP sites. The main enzyme of S.
      cerevisiae. Apn1, provides cellular resistance to oxidants (e.g., H2O2) or
      alkylating agents, and limits the spontaneous mutation rate. AP endonucleases
      from other species can replace Apn1 function in yeast to different extents. We
      studied the main human enzyme, Ape, with respect to its incision specificity in
      vitro and the expression of the APE gene in vivo. The results suggest that Ape
      evolved to act preferentially on AP sites compared to deoxyribose fragments
      located at oxidative strand breaks and that the incision modes of Ape and Apn1
      may be fundamentally different. We also defined the functional APE promoter, and
      showed that APE expression is transiently downregulated during the regeneration
      of epidermis after wounding. This latter effect may lead to a window of
      vulnerability for DNA damage and perhaps mutagenesis during the healing of
      epidermal and other wounds. Such unexpected effects on the expression of DNA
      repair enzymes need to be taken into account in analyzing the susceptibility of
      different tissues to carcinogens.

PMID- 9255584
TI  - Recent molecular advances in the approach to early lung cancer detection and
      intervention.
AB  - Lung cancer is a major contributor to overall cancer mortality. Detecting lung
      cancer while it is still a localized process is a long-cherished goal for
      improving the outcome of this disease. Recent developments suggest that we are
      approaching this capability. We next have to think about how to implement a
      change in our approach to lung cancer management to derive the benefit of better
      detection capability. This is an area in which our growing understanding of lung
      cancer biology is providing clues on improving the inhibition of cancer
      progression.

PMID- 9255585
TI  - Native cellular fluorescence and its application to cancer prevention.
AB  - Native cellular fluorescence (NCF) represents the innate capacity of tissues to
      absorb and emit light of specified wavelengths. Recent advances in optical
      engineering and computer technology have provided the, opportunity to measure NCF
      characteristics of various tissues in vivo. This report will briefly review the
      current status of NCF analysis of various neoplastic tissues. The status of
      investigations involving the upper aerodigestive tract will be discussed. Though
      initial results demonstrate that neoplastic tissues can be discriminated from
      normal mucosa by NCF analysis, the biologic basis of this difference remains
      uncertain. This report will also emphasize that the ability to screen for cancer
      in aerodigestive mucosa may be enhanced through the assessment of multiple
      emission and excitation wavelengths. The true nature of the cellular fluorophores
      responsible for these mucosal spectral characteristics should be more fully
      defined in coming years.

PMID- 9255586
TI  - Perspectives in cancer chemoprevention.
AB  - Cancer chemoprevention can be defined as prevention of cancer by the
      administration of one or more chemical entities, either as individual drugs or as
      naturally occurring constituents of the diet. Based largely on the time period
      that chemopreventive agents exhibit activity in animal models of carcinogenesis,
      they can be classified as inhibitors of carcinogen formation, blocking agents,
      and suppressing agents. The majority of compounds that inhibit the formation of
      carcinogens prevent the formation of nitrosamines from secondary amines and
      nitrite in an acidic environment. Blocking agents are inhibitors of tumor
      initiation, while suppressing agents are inhibitors of tumor
      promotion/progression. Many well-characterized chemopreventive agents act at one
      or more steps in both tumor initiation and promotion/progression. The objective
      of this paper is to provide a general discussion of the mechanisms through which
      chemopreventive agents inhibit carcinogenesis. Examples of agents that act
      through these mechanisms are given; however, a complete listing of effective
      chemopreventive agents is not possible within the context of this paper. At the
      conclusion is a brief discussion of future prospects in cancer chemoprevention
      and obstacles to overcome.

PMID- 9255588
TI  - Chemoprevention by inducers of carcinogen detoxication enzymes.
AB  - One of the major mechanisms of chemical protection against carcinogenesis,
      mutagenesis, and other forms of toxicity mediated by electrophiles is the
      induction of enzymes involved in their metabolism, particularly phase 2 enzymes
      such as glutathione S-transferases (GSTs), uridine diphosphate
      glucuronosyltransferases, and NAD(P)H:quinone reductase. Furthermore, induction
      of phase 2 enzymes appears to be a sufficient condition for obtaining
      chemoprevention and can be achieved in many target tissues by administering any
      of a diverse array of naturally occurring and synthetic chemical agents. One
      class of chemopreventive agents, 1,2-dithiole-3-thiones, was developed on the
      basis of their potent activity in rodent tissues as inducers of GSTs. A
      substituted dithiolethione, oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3
      thione], is an effective inhibitor of aflatoxin B1-mediated hepatocarcinogenesis
      in the rat. Oltipraz produces dramatic decreases in the levels of aflatoxin-DNA
      adducts in the liver as well as in the urinary levels of the depurination product
      aflatoxin-N7-guanine. Corresponding increases are seen in the biliary elimination
      of aflatoxin-glutathione conjugates. Administration of oltipraz results in 3- to
      4-fold increases in hepatic cytosolic GST activities and mRNA levels for some
      alpha, mu and pi isoforms. Nuclear run-on assays have indicated that oltipraz
      treatment elevates rates of transcription of some GST subunits. In the rat,
      induction of phase 2 enzymes by oltipraz is mediated, at least in part, through
      the antioxidant response element in the 5' flanking region of these genes.
      Although oltipraz has a very short plasma half-life, elevations in the levels of
      some GST isoforms can persist up to 1 week after dosing with oltipraz.
      Concordantly, intermittent dosing schedules (i.e., once a week) are nearly as
      effective as daily interventions for inhibition of aflatoxin-mediated hepatic
      tumorigenesis. The protective efficacy of daily and weekly administration of
      oltipraz to people in Qidong, People's Republic of China, who are at high risk
      for aflatoxin exposure and subsequent development of hepetocellular carcinoma, is
      currently under evaluation.

PMID- 9255587
TI  - Approaches to chemoprevention of lung cancer based on carcinogens in tobacco
      smoke.
AB  - Chemoprevention may be one way to prevent lung cancer in smokers who are
      motivated to quit but cannot stop. The approach to chemoprevention of lung cancer
      described in this article is based on an understanding of the lung carcinogens
      present in tobacco smoke. The available data indicate that the compounds in
      cigarette smoke most likely involved in the induction of lung cancer in humans
      are the complex of polynuclear aromatic hydrocarbons typified by benzo[a]pyrene
      (B[a]P) and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK). A large number of compounds are now available that inhibit lung
      tumorigenesis by B[a]P or NNK in rodents. Inhibition of NNK-induced lung
      carcinogenesis by phenethyl isothiocyanate (PEITC) and inhibition of B[a]P
      induced lung carcinogenesis by benzyl isothiocyanate (BITC) are discussed as
      examples. Studies with PEITC in rodents clearly demonstrate that it inhibits NNK
      induced lung tumorigenesis by inhibiting the metabolic activation of NNK. Similar
      changes appear to occur in humans according to data generated in smokers who ate
      watercress, a source of PEITC. It is likely that mixtures of chemopreventive
      agents with activity against carcinogens in tobacco smoke, such as NNK and B[a]P,
      will be useful in chemoprevention of lung cancer in smokers. Furthermore, there
      is a need to develop suppressing agents for lung cancer that might be applicable
      in both smokers and ex-smokers.

PMID- 9255590
TI  - Cancer chemoprevention and therapy by monoterpenes.
AB  - Monoterpenes are found in the essential oils of many plants including fruits,
      vegetables, and herbs. They prevent the carcinogenesis process at both the
      initiation and promotion/progression stages. In addition, monoterpenes are
      effective in treating early and advanced cancers. Monoterpenes such as limonene
      and perillyl alcohol have been shown to prevent mammary, liver, lung, and'other
      cancers. These compounds have also been used to treat a variety of rodent
      cancers, including breast and pancreatic carcinomas. In addition, in vitro data
      suggest that they may be effective in treating neuroblastomas and leukemias. Both
      limonene and perillyl alcohol are currently being evaluated in phase I clinical
      trials in advanced cancer patients. The monoterpenes have several cellular and
      molecular activities that could potentially underlie their positive therapeutic
      index. The monoterpenes inhibit the isoprenylation of small G proteins. Such
      inhibitions could alter signal transduction and result in altered gene
      expression. The results of a new gene expression screen-subtractive display-have
      identified or confirmed several up- or downregulated genes in regressing mammary
      carcinomas. For example, these regressing tumors overexpress the mannose 6
      phosphate/IGF II receptor. The product of the gene both degrades the mammary
      tumor mitogen IGF II and activates the cytostatic factor TGF-beta. These and
      other alterations in the gene expression of mammary carcinomas lead to a G1 cell
      cycle block, followed by apoptosis, redifferentiation, and finally complete tumor
      regression in which tumor parenchyma is replaced by stromal elements. It is
      likely that monoterpenes prevent mammary cancer during their progression stage by
      mechanisms similar to those that occur during therapy. In contrast, prevention of
      mammary cancer by polycyclic hydrocarbons such as 7,12-dimethylbenz[a]anthracene
      occur by the induction of detoxifying phase II hepatic enzymes.

PMID- 9255589
TI  - Polyphenols as inhibitors of carcinogenesis.
AB  - Many polyphenolic compounds have demonstrated anticarcinogenic activities in
      animal models. These compounds include flavanone, flavonols, isoflavone, and
      catechins. In this article, tea catechins will be used as an example to
      illustrate current research in this area. Many laboratory studies have
      demonstrated the inhibition of tumorigenesis in animal models by different tea
      preparations. The animal models include tumorigenesis in the mouse lung, rat and
      mouse esophagi, mouse forestomach, mouse skin, mouse duodenum, rat small
      intestine, rat and mouse livers, and rat colon. In most of the studies, the
      inhibitory activity of tea could be demonstrated when tea preparations were given
      either during or after the carcinogen treatment period. Black tea was also
      effective, although the activity was weaker than green tea in some experiments.
      Decaffeinated tea preparations were also active in many model systems. The
      molecular mechanisms for these broad inhibitory actions are not fully understood.
      They are most likely related to the biochemical actions of the tea polyphenols,
      which include antioxidative activities and inhibition of cell proliferation and
      of tumor promotion-related activities. The effect of tea consumption on human
      cancers is not clear in spite of numerous investigations. The bioavailability and
      pharmacokinetics of tea polyphenols are being studied in animals and humans to
      provide a basis for more quantitative analyses on the effect of tea on
      carcinogenesis. More mechanistic and dose-response studies will help us to
      understand the effects of tea consumption on human carcinogenesis.

PMID- 9255592
TI  - Roles of retinoids and their nuclear receptors in the development and prevention
      of upper aerodigestive tract cancers.
AB  - Vitamin A analogs (retinoids) suppress oral and lung carcinogenesis in animal
      models and prevent the development of second primary tumors in head, neck, and
      lung cancer patients. These effects result from changes in the expression of
      genes that regulate cell growth and differentiation. Retinoic acid receptors
      (RARs; -alpha, -beta, and -gamma) and retinoid X receptors (RXRs; -alpha, -beta,
      and, -gamma) are retinoid-activated transcription factors, which mediate effects
      of retinoids on gene expression. Therefore, alterations in receptor expression or
      function could interfere with the retinoid signaling pathway and thereby enhance
      cancer development. We found that the expression of RAR beta was suppressed in
      more than 50% of oral and lung premalignant lesions in individuals without cancer
      and in dysplastic lesions adjacent to cancer and in malignant oral and lung
      carcinomas. The expression of the other receptors was not different among normal,
      dysplastic, and malignant oral tissues. However, the expression of RAR gamma and
      RXR beta was somewhat decreased in lung cancers. These results show that RAR beta
      expression is lost at early stages of carcinogenesis in the aerodigestive tract
      and support the hypothesis that the loss of RAR beta expression may facilitate
      the development of some of these cancers.

PMID- 9255591
TI  - Chemoprevention of ultraviolet radiation-induced skin cancer.
AB  - The use of chemical and physical sunscreening agents has increased dramatically
      during the last two to three decades as an effective means of preventing sunbum.
      The use of high sunprotection factor sunscreens has also been widely promoted for
      the prevention of skin cancer, including melanoma. Whereas sunscreens are
      undoubtedly effective in preventing sunbum, their efficacy in preventing skin
      cancer, especially melanoma, is currently under considerable debate. Sunscreens
      have been shown to prevent the induction of DNA damage that presumably results
      from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has
      been identified as an initiator of skin cancer formation. However, both
      laboratory and epidemiological studies indicate that sunscreens may not block the
      initiation or promotion of melanoma formation. These studies suggest that the
      action spectrum for erythema induction is different than the action spectrum for
      the induction of melanoma. Indeed, recent reports on the wavelength dependency
      for the induction of melanoma in a fish model indicate that the efficacy of
      ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude
      higher than would be predicted from the induction of erythema in man or
      nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin
      cancer have also been reported. Low levels and degree of unsaturation of dietary
      fats protect against UVR-induced skin cancer in mice humens. Compounds with
      antioxidant activity, including green tea extracts (polyphenols), have been
      reported to inhibit UVR-induced skin carcinogenesis.

PMID- 9255594
TI  - Effect of motor cortical kindling on subsequent ventral hippocampal kindling and
      the role of the corpus callosum in the cat.
AB  - The effect of bilateral motor cortical (MC) kindling on subsequent unilateral
      ventral hippocampal (VHIPP) kindling was studied in four cats with the corpus
      callosum (CC) intact and five cats with the CC bisected, compared with nine cats
      with unilateral VHIPP kindling. Subsequent VHIPP kindling in CC-intact cats
      resulted in the modified development of limbic seizures to ipsilateral, not
      contralateral, focal motor seizures in one of four cats, significantly greater
      seizure regressions from generalized convulsive seizure stage to earlier seizure
      stages and delayed onset of focal motor seizures and generalized convulsions in
      partial onset generalized convulsions. CC bisection reduced the degree of seizure
      regression from generalized convulsive seizure stage to earlier stages,
      facilitated the development of the last limbic seizure to the first generalized
      convulsive seizure, accentuated hemiconvulsions and asymmetrical generalized
      convulsions and delayed the onset of generalized convulsions in partial onset
      generalized convulsions. The modified seizure development was also induced in
      three of five CC-bisected cats. Results indicate that bilateral MC kindling
      induces inhibitory effects on subsequent unilateral VHIPP kindling and the
      modified ictal progress from the VHIPP to the contralateral hemispheric motor
      structures and also that CC bisection interferes with the bilateralization and
      synchronization of convulsions, but reduces the inhibition of previously
      established MC kindling against VHIPP kindling and facilitates the development of
      focal motor seizures to secondarily generalized convulsions.

PMID- 9255593
TI  - Dietary restrictions and cancer.
AB  - Dietary restriction (DR) alters a significant environmental factor in
      carcinogenesis, dietary intake, thus inhibiting both spontaneous and induced
      tumorigenesis. Potential mechanisms for the inhibition of spontaneous cancer may
      include the effects of DR to do the following: decrease body weight, which
      decreases cellular proliferation and increases apoptosis in a number of organs
      that increase and decrease with body size; decrease body temperature, thereby
      lowering the amount of endogenous DNA damage temperature generates; decrease
      oxidative damage, by increasing antioxidant damage defense systems; decrease,
      generally, cellular proliferation; and protect the fidelity of the genome by
      decreasing DNA damage, increasing DNA repair, and preventing aberrant gene
      expression. Potential mechanisms for reducing induced tumor incidence include
      lowering agent activation, changing agent disposition, decreasing the adducts
      most associated with agent toxicity, and inhibiting tumor progression through
      mechanisms similar to those that can effect spontaneous tumorigenesis. As a
      method to control a major source of environmental cancer, and as the major
      modulator of the agent induction of this disease, understanding how DR works may
      significantly contribute to the efforts to explain how diet impacts on
      development of cancer in the United States, and may suggest methods to reduce the
      adverse impacts of other environmental agents on the disease.

PMID- 9255595
TI  - Pharmacokinetics and muscle histopathology of intramuscular valproate.
AB  - To determine the safety and pharmacokinetics of parenteral sodium valproate
      healthy mature greyhound dogs, were given intramuscular injections following
      intravenous injections. Dosings intravenously and intramuscularly were at 20, 40
      and 60 mg/kg in the three groups. Intravenous infusion rates were constant.
      Sodium valproate solution concentrations of 300, 400 and 500 mg/ml were
      administered. Intramuscular valproate was quickly absorbed. Bio-availability
      approached 70%. Half life of 120 min was calculated. Toxic muscle necrosis was
      observed at all concentrations. Dosing valproate intramuscularly in humans is
      problematic in view of the muscle damage. Despite tissue damage sodium valproate
      was well absorbed intramuscularly. The intravenous injection of valproate at high
      concentrations, large doses and fast infusion rates produced no evidence of
      cardiotoxicity and levels of 180 micrograms/ml.

PMID- 9255597
TI  - The cerebral hemisphere of the turtle in vitro. An experimental model with
      spontaneous interictal-like spikes for the study of epilepsy.
AB  - Slice in vitro preparations have been useful to study the cellular basis of some
      epilepsy related phenomena. However, the cellular mechanisms that generate ictal
      activity remain poorly understood. Therefore, an experimental in vitro model
      capable of generating seizure-like activity might contribute to the study of the
      cellular basis of seizures. The outstanding resistance to hypoxia of turtles
      enabled us to develop an in vitro preparation that keeps all the cortical neural
      circuitry intact. A whole cerebral hemisphere of the turtle Chrysemys d'orbigny
      was isolated (n = 45) and simultaneous electrographic and intracellular
      recordings were performed in the medial cortex. The electrographic activity was
      composed by a non-rhythmic, low-voltage (10-20 microV) activity interrupted by
      spontaneous large (50-700 microV) sharp waves (LSWs). The cellular counterpart of
      the LSWs was often a burst of action potentials that resembled the paroxysmal
      depolarisation shift (PDS). Bicuculline (20-40 microM, n = 20) increased the
      interictal-like activity and in some preparations (3 out of 20) provoked seizure
      like events. Complex bursting activity and a slow afterhyperpolarisation were
      cellular events observed during seizures. We propose that this model might be a
      valuable tool for the study the cellular mechanisms involved in the transition
      from the interictal to the ictal activities.

PMID- 9255596
TI  - AWD 140-190: a new anticonvulsant with a very good margin of safety.
AB  - The anticonvulsant activity of the novel drug AWD 140-190 (4-(p-bromophenyl)-3
      morpholino-1H-pyrrole-2-carboxylic acid methyl ester) was evaluated in animal
      models of epileptic seizures. AWD 140-190 was active at nontoxic doses after oral
      and intraperitoneal administration in rats and mice in a range of anticonvulsant
      tests. The compound was active against electrically-induced seizures (MES, ED50
      rat p.o. = 2.47 mg/kg), in a genetic animal model the DBA/2 mouse, and in
      corneally kindled rats. It was not active against seizures induced chemically by
      pentylenetetrazole, bicuculline and strychnine. Effective doses in mice following
      both oral and intraperitoneal administration are similar indicating good oral
      absorption. During 14 days chronic oral treatment of mice with 10 mg/kg, no
      development of tolerance was observed. The protective indices (TD50/MES ED50) in
      rats and mice following oral administration are favorable when compared to
      phenytoin, carbamazepine and valproate. No motor impairment, evaluated with the
      rotarod test and by observation in the open field test, was observable following
      oral administration of doses up to 500 mg/kg. There was no influence on
      spontaneous motility and learning performance in rats and no interaction with
      ethanol in mice after administration of doses which are above anticonvulsant
      effective doses indicating the absence of central side effects. AWD 140-190 thus
      presents an orally active and safe anticonvulsant agent, which is structurally
      unrelated to anticonvulsants currently used.

PMID- 9255598
TI  - MRI volumetry and T2 relaxometry of the amygdala in newly diagnosed and chronic
      temporal lobe epilepsy.
AB  - Little is known about the appearance and severity of amygdaloid damage in
      temporal lobe epilepsy, particularly in its early stages. In the present magnetic
      resonance imaging study, we measured amygdaloid volumes and T2 relaxation times
      in 29 patients with newly diagnosed and in 54 patients with chronic temporal lobe
      epilepsy. The control population included 25 normal subjects. In the newly
      diagnosed patients, the mean amygdaloid volume did not differ from that in
      controls. Also, in the chronic patients the mean amygdaloid volume did not differ
      from that in controls or in newly diagnosed patients. However, in 19% of the
      chronic patients the amygdaloid volume was reduced by at least 20%. Moreover, in
      all of the epilepsy patients, both chronic and newly diagnosed, we found an
      inverse correlation between the number of epileptic seizures the patient had
      experienced and the amygdaloid volume on the focal side (focus on the left, r = 
      0.371, P < 0.01; focus on the right, r = -0.348, P < 0.05). The mean T2
      relaxation time in newly diagnosed or chronic patients did not differ from each
      other or from control values. However, the T2 relaxation time of the left
      amygdala was > or = 111 msec (i.e., > or = 2 S.D. over the mean T2 time of the
      left amygdala in control subjects) in seven (10%) patients, one of which was
      newly diagnosed and six were chronic. The T2 time of the right amygdala was
      prolonged in eight (12%) patients, three of which were newly diagnosed and five
      were chronic. We did not find any clear asymmetries in amygdaloid volumes or T2
      relaxation times between the ipsilateral and contralateral sides relative to
      seizure focus. According to the present findings, signs of amygdaloid damage were
      observed in approximately 20% of patients with temporal lobe epilepsy, most of
      which had chronic epilepsy.

PMID- 9255600
TI  - Comparison of the preclinical anticonvulsant profiles of tiagabine, lamotrigine,
      gabapentin and vigabatrin.
AB  - Tiagabine is a novel antiepileptic drug which has clinical efficacy against
      complex refractory and myoclonic seizures. The anticonvulsant mechanism of action
      of tiagabine results from its blockade of neuronal and glial GABA-uptake, thereby
      increasing GABA levels in the synaptic cleft. Here we present a comparison of the
      preclinical anticonvulsant profile of tiagabine with that of lamotrigine,
      gabapentin and vigabatrin in the following tests (all antiepileptic drugs were
      administered i.p.): seizures induced by pentylentetrazol (PTZ), 6,7-dimethoxy-4
      ethyl-b-carboline-3-carboxylate (DMCM) and maximal electroshock (MES); sound
      induced seizures in DBA/2 mice and finally acute amygdala kindled seizures.
      Tiagabine was the most potent drug in antagonizing tonic convulsions induced by
      PTZ, DMCM and sound induced seizures in DBA/2 mice with ED50 values of 2, 2 and 1
      mumol/kg, respectively, followed by lamotrigine with ED50 values of 9, 43 and 6
      mumol/kg, respectively. Gabapentin and vigabatrin had ED50 values in the same
      tests of 185, 452, 66 mumol/kg and 2322, > 7740, 3883 mumol/kg, respectively.
      Tiagabine was the only drug capable of blocking PTZ-induced clonic convulsions
      (ED50 = 5 mumol/kg), an effect seen at low but not high doses of tiagabine.
      Lamotrigine was the only drug which antagonized tonic convulsions in the MES test
      (ED50 = 36 mumol/kg). Therapeutic index (TI) of antiepileptic drugs in NMRI- and
      DBA/2-mice ranked with decreasing TI lamotrigine > gabapentin > vigabatrin >
      tiagabine. All drugs reduced the generalized seizures in amygdala kindled rats,
      but tiagabine and gabapentin furthermore attenuated afterdischarge duration of
      amygdala kindled seizures. However, an ED50 value against amygdala kindled focal
      seizures was only obtained for tiagabine (36 mumol/kg). The data here presented
      show that tiagabine, lamotrigine, gabapentin and vigabatrin possess different
      preclinical anticonvulsant profiles which is of relevance to the clinical
      anticonvulsant profiles of the drugs.

PMID- 9255599
TI  - Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05
      2090, not acting preferentially on GAT-1.
AB  - Two novel nipecotic acid derivatives, 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(4
      methoxyphenyl)-4-piperidino l (NNC 05-2045) and 1-(3-(9H-Carbazol-9-yl)-l-propyl)
      4-(2-methoxyphenyl)-4-piperidino l (NNC 05-2090) have been tested for inhibition
      of gamma-amino butyric acid (GABA) transporters in synaptosomal preparations of
      rat cerebral cortex and inferior colliculus and found to differ markedly from
      gabitril (tiagabine), a selective GAT-1 inhibitor. IC50 values for inhibition of
      [3H]GABA uptake into synaptosomes from cerebral cortex for NNC 05-2045 and NNC 05
      2090 were 12 +/- 2 and 4.4 +/- 0.8 microM, respectively. In synaptosomes from
      inferior colliculus in the presence of 1 microM 1-(2
      (((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic
      acid (NNC 05-0711), a highly potent and selective GAT-1 inhibitor, IC50 values
      for inhibition of [3H]GABA uptake were 1.0 +/- 0.1 and 2.5 +/- 0.7 microM,
      respectively. A receptor profile showed that NNC 05-2045 has binding affinities
      to sigma-, alpha 1- and D2-receptors of 113, 550 and 122 nM, respectively. NNC 05
      2090 displayed alpha 1- and D2-receptor affinity of 266 and 1632 nM,
      respectively. The anticonvulsant action of both compounds was tested in four
      rodent models after intra peritoneal (i.p.) injection. Both NNC 05-2090 dose
      dependently inhibited sound-induced tonic and clonic convulsions in DBA/2 mice
      with ED50 values of 6 and 19 mumol/kg, respectively. NNC 05-2045 also antagonized
      sound-induced seizures in genetic epilepsy prone rats (GEP rats) with ED50 values
      against wild running, clonic and tonic convulsions of 33, 39 and 39 mumol/kg,
      respectively (NNC 05-2090 was not tested in GEP rats). Both NNC 05-2045 and NNC
      05-2090 dose-dependently antagonized tonic hindlimb extension in the maximal
      electroshock (MES) test with ED50 values of 29 and 73 mumol/kg, respectively. In
      amygdala kindled rats NNC 05-2045 and NNC 05-2090 significantly (P < 0.05)
      reduced generalized seizure severity (seizure grade 3-5) at highest doses (72-242
      mumol/kg) and NNC 05-2090 also significantly reduced afterdischarge duration at
      these doses (P < 0.05). These data show that inhibition of GABA uptake through
      non-GAT-1 transporters has different anticonvulsant effects than selective GAT-1
      inhibitors (e.g. tiagabine) in that enhanced efficacy against MES and reduced
      efficacy against kindled seizures is observed. Although a contribution of
      adrenergic agonistic effects cannot be entirely ruled out, it is proposed that
      inhibition of GAT-3 (mouse GAT4) is primarily responsible for the anticonvulsant
      action of these two nipecotic acid derivatives in MES, amygdala kindled rats and
      in sound-induced seizures in GEP-rats and DBA/2 mice.

PMID- 9255601
TI  - Status epilepticus induced by pilocarpine and picrotoxin.
AB  - Since its original description over 10 years ago, the pilocarpine model of status
      epilepticus (SE) has gained considerable attention. Much work has been done with
      the model in order to characterize the involvement of different brain structures
      in seizure genesis and spread. Electrophysiological studies of temporal lobe
      epileptic slices of both human and animal models, have failed to reveal
      hyperexcitability, unless blockade of GABAergic inhibition is performed. Thus, we
      have decided to evaluate potential contributions of picrotoxin, a GABAA channel
      blocker, on pilocarpine-induced SE. Animals injected with three-specific dose
      combinations (pilocarpine dose/picrotoxin dose), 150/0.5, 75/1.5 and 50/2.0
      mg/kg, evoked status epilepticus (SE) within 23, 31 and 27 min, respectively.
      Ictal events and EEG spikes were initially observed either in the amygdala or in
      the hippocampus, with a later spread to cerebral cortex. Neuropathological
      analysis, performed 5-7 days after SE, has shown a high degree of cell loss
      predominantly in the piriform cortex, amygdala, hippocampus, thalamus and
      substantia nigra. Mortality rates for 150/0.5, 75/1.5 and 50/2.0 mg/kg
      (pilocarpine dose/picrotoxin dose) were 53, 42 and 51%, respectively. Single
      injections of 150 mg/kg of pilocarpine or 3 mg/kg of picrotoxin did not evoke any
      form of sustained epileptic activity. Previous studies in which simultaneous
      injections of other GABAA antagonists (i.e. bicuculline) and pilocarpine were
      performed, did not show clear evidences of a synergistic action between these two
      systems. The present study reveals a proconvulsant role for picrotoxin when co
      administered with subconvulsant doses of pilocarpine. Possible mechanisms that
      might account for the interactions between the cholinergic and GABAergic systems
      in regard to epileptogenesis are discussed.

PMID- 9255602
TI  - Effects of epidermal growth factor administration on repair of acetic acid
      induced colonic ulcerations in rats.
AB  - The effect of subcutaneous and luminal epidermal growth factor (EGF)
      administration on acetic acid-induced colonic ulceration was determined in adult
      rats. Application of acetic acid to the distal colonic lumen caused epithelial
      denudation, mucosal ulceration and inflammation in the exposed segment. Re
      epithelialization was detectable 5 to 7 days later, with near-complete resolution
      of the lesion by 14 days post-injury. Luminal EGF (1.6 mg/kg bw/day) or
      subcutaneous EGF (200 micromilligrams/kg bw/day), administered for 4 or 6 days
      from the time of ulceration failed to enhance re-epithelialization of the acid
      exposed segment. However, mucosal and submucosal thickening was attenuated 20-40%
      by subcutaneous EGF, reflecting a reduction in edema. Luminal EGF had a similar
      but less substantial effect in the submucosa, but was more effective at
      attenuating muscularis thickening adjacent to the lesion. In conclusion,
      administration of exogenous EGF for up to 6 days failed to enhance re
      epithelialization of acetic acid-induced colonic ulcerations but did attenuate
      the associated edematous response.

PMID- 9255603
TI  - The Csk-like proteins Lsk, Hyl, and Matk represent the same Csk homologous kinase
      (Chk) and are regulated by stem cell factor in the megakaryoblastic cell line
      MO7e.
AB  - Recently, the cDNAs for Lsk, Matk and Hyl, three Csk-related protein tyrosine
      kinases, have been cloned. We have examined the relationship of Lsk, Matk and
      Hyl, and found that the gene for each of these proteins is localized to the same
      region of human chromosome 19. Further, the proteins encoded by Lsk and Matk
      cDNAs are immunologically similar. These data strongly suggest that Lsk, Hyl and
      Matk are the same gene product. Previous reports demonstrating expression of Hyl
      and Matk in hematopoietic lineages led us to investigate the regulation of Lsk
      expression in response to stem cell factor (SCF) and granulocyte-macrophage
      colony stimulating factor (GM-CSF) in M07e, a human leukemic cell line. Induction
      of Lsk/Hyl/Matk protein and mRNA was observed after treatment with SCF but not
      with GM-CSF. GM-CSF and IL-3, potent mitogens, had no effect on Lsk/Hyl/Matk
      expression. In contrast, PMA induced Lsk/Hyl/Matk but did not stimulate
      proliferation. Therefore, induction of Lsk/ Hyl/Matk does not correlate with the
      capacity to stimulate proliferation. None of the stimuli examined increased Csk
      protein or mRNA expression. These data demonstrate differential regulation of Csk
      family members by cytokines and suggest a role for Lsk/ Hyl/Matk in responses
      mediated by SCF and PMA. Further, our data demonstrate that, as has been seen in
      blood monocytes, cytokine driven translational control of Lsk/Hyl/ Matk is likely
      a critical mode of regulation. Lastly, since our studies strongly suggest that
      the Lsk, Hyl and Matk kinases are related and regulated distinctly from Csk, we
      and several of the original authors have agreed to rename this kinase the Csk
      homologous kinase (Chk).

PMID- 9255604
TI  - Neutralising antibodies to the granulocyte colony-stimulating factor receptor
      recognise both the immunoglobulin-like domain and the cytokine receptor
      homologous domain.
AB  - To define regions of the granulocyte colony-stimulating factor (G-CSF) receptor
      that are important for ligand binding, neutralising monoclonal antibodies to the
      human receptor have been produced. Eleven antibodies recognised six different
      receptor epitopes. Antibodies from three of the epitope groups were able to
      detect the receptor by western blotting but did not inhibit G-CSF binding. The
      other three antibody groups inhibited G-CSF binding either completely (groups 1
      and 2) or partially (group 3). All the antibodies inhibited proliferation of
      BA/F3 cells expressing the G-CSF receptor to varying extents. By using human
      marine chimeric receptors, the binding sites of the antibodies were mapped to the
      immunoglobulin-like domain (groups 1 and 3), the cytokine receptor homologous
      domain (group 2) or the fibronectin type III domains (groups 4 to 6). These
      results show that the immunoglobulin-like and cytokine receptor homologous
      domains of the receptor are important for ligand binding and subsequent
      signalling.

PMID- 9255605
TI  - Evidence for a local action of growth hormone in embryonic tooth development in
      the rat.
AB  - Studies in non-dental embryonic tissues have suggested that an interaction
      between growth hormone and its receptor may play a role in growth and development
      before the foetal pituitary gland is competent. This study reports the
      distribution of growth hormone, its receptor and binding protein in developing
      rat tooth germs from embryonic day 17 to 21 and postnatal day 0 using antibodies
      specific for each of these proteins. Four foetal rats were processed at each time
      point (E17, E18, E20/21 and postnatal day 0). Following routine fixation and
      paraffin embedding, sections were treated with antisera to rat growth hormone,
      rat growth hormone binding protein and growth hormone receptor. Localization of
      antibody/antigen complexes was subsequently visualized by addition of
      biotinylated IgG and reaction with streptavidin peroxidase and diaminobenzidine.
      Assessment of the level of staining was qualitative and based on a subjective
      rankings ranging from equivocal to very strong staining. Overall, growth hormone
      and its binding protein were located both in the cellular elements and throughout
      the extracellular matrix, whereas the growth hormone receptor showed an
      exclusively intra-cellular location. All three proteins were detectable in cells
      of the dental epithelium and mesenchyme at the primordial bud stage (E17) which
      occurs prior to expression of pituitary growth hormone. At the cap stage of
      odontogenesis (E18-19), numerous cells in both the dental epithelium and
      mesenchyme were intensely immunoreactive for growth hormone, its binding protein
      and receptor. In the succeeding early bell stage (E20-21), most of the
      mesenchymal cells in the dental pulp were mildly positive for these proteins,
      while the dental epithelium and adjacent mesenchyme were more immunoreactive. At
      the late bell stage (postnatal day 0), all three proteins were localized in
      dental epithelium, differentiating mesenchymal cells the cuspal surface facing
      the epithelial-mesenchymal interface, preodontoblasts, and odontoblasts forming
      dentine. From these observations, immunoreactive growth hormone, its receptor and
      binding protein appear to be expressed in odontogenic cells undergoing
      histodifferentiation, morphodifferentiation and dentinogenesis in a cell-type and
      stage-specific pattern throughout embryonic tooth development. This suggests the
      possibility that growth hormone, or a growth hormone-like protein, plays a
      paracrine/autocrine role in tooth development in utero.

PMID- 9255606
TI  - Self renewal of embryonic stem cells in the absence of feeder cells and exogenous
      leukaemia inhibitory factor.
AB  - To evaluate the role of leukaemia inhibitory factor (LIF) for maintaining
      pluripotent embryonic stem (ES) cells in culture, we established several
      exogenous LIF-independent ES cell lines by continuous passaging in culture. The
      newly established ES cells, Kli and CBli, sustained their growth and remained
      undifferentiated in LIF-deficient medium. Analysis of chimaeric animals, produced
      with the beta-galactosidase transgenic Kli ES cells, revealed that LIF
      independent ES cells can contribute to all embryonic germ layers. There was no
      detectable LIF protein in ES cell conditioned medium, and no upregulation of LIF
      mRNA was found. The addition of neutralising anti-LIF antibodies was not
      sufficient to abrogate the self renewal of the Kli ES cells. These studies
      suggest that the signalling pathway involving diffusible LIF can be bypassed for
      maintaining the pluripotency in culture, and indicate a considerable
      heterogeneity in growth factor dependence and differentiation of different ES
      cells.

PMID- 9255607
TI  - Epo-induced hemoglobinization of SKT6 cells is mediated by minimal cytoplasmic
      domains of the Epo or prolactin receptors without modulation of GATA-1 or EKLF.
AB  - Interaction of erythropoietin with its type 1 receptor is essential to the
      development of late erythroid progenitor cells. Through the ectopic expression of
      receptor mutants in lymphoid and myeloid cell lines, insight has been gained
      regarding effectors that regulate Epo-induced proliferation. In contrast,
      effectors that regulate Epo-induced differentiation events (e.g. globin gene
      expression) are largely undefined. For in vitro studies of this pathway,
      erythroleukemic SKT6 cell sublines have been isolated which stably and
      efficiently hemoglobinize in response to Epo. Epo rapidly activated Jak2, STAT5
      and detectably STATs 1 and 3, while no effects on GATA-1, EKLF or STAT5
      expression were observed. Finally, efficient hemoglobinization of SKT6 cells was
      shown to be mediated by chimeric receptors comprised of the EGF receptor
      extracellular domain and truncated cytoplasmic subdomains of either the Epo
      receptor or the prolactin Nb2 receptor. This work further establishes SKT6 cells
      as an important model for studies of Epo-stimulated differentiation, and shows
      that this signaling pathway is promoted by a limited set of membrane-proximal
      receptor domains and effectors.

PMID- 9255608
TI  - Effects of transforming growth factor-beta 1 and phorbol ester on PAI-1 and PA
      genes in human lung cells.
AB  - Transforming growth factor-beta (TGF-beta) mediates the production of
      extracellular matrix proteins, proteases and protease inhibitors in epithelial
      cells. Both TGF-beta and phorbol-12-myristate-13-acetate (PMA) exert both
      positive and negative effects on mitogenesis in these as well as other cell
      types. Phorbol esters act through stimulation of protein kinase C (PKC) and are
      among the most potent tumor promoters known. The present study was conducted to
      determine whether the effect of TGF-beta in human non-small cell lung cancer
      (NSCLC) and normal human bronchial epithelial (NHBE) cells parallels that of the
      phorbol esters and whether this effect of TGF-beta involves PKC. TGF-beta 1 and
      PMA increased expression of TGF-beta 1 mRNA 24 hr after their addition to both
      NSCLC and NHBE cells. The effects of these agents on expression of the mRNAs for
      TGF-beta 2 and TGF-beta 3 were more complex; while TGF-beta 2 and TGF-beta 3
      mRNAs increased transiently in response to TGF-beta 1 in NHBE cells and TGF-beta
      3 mRNA increased transiently in some NSCLC cells, expression of these mRNAs
      decreased in most of these cells in response to PMA with the exception of the
      carcinoid NCI-H727 where TGF-beta 2 mRNA increased dramatically, TGF-beta 1 and
      PMA both caused a persistent increase in expression of the mRNAs for both
      plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator (PA) up to 24
      hr in most NSCLC cells, with the increase in PAI-1 mRNA beginning several hours
      before that of PA mRNA. In contrast, while TGF-beta 1 also increased expression
      of PAI-1 mRNA in NHBE cells, the expression of PA mRNA decreased simultaneously.
      The effect of PMA on PAI-1 and PA mRNAs was opposite of TGF-beta 1 in these
      cells, with expression of PAI-1 mRNA decreasing and PA mRNA increasing after
      addition of PMA. These data show that there is parallel regulation of the genes
      for TGF-beta 1, PAI-1 and PA by TGF-beta 1 and PMA in NSCLC, but differential
      regulation of the genes for PAI-1 and PA by these agents in NHBE cells. The
      responses of the mRNAs and proteins of TGF-beta 1, PAI-1 and PA to TGF-beta 1 and
      PMA were inhibited by the serine/ threonine kinase inhibitor H7 in NSCLC cells.
      Treatment of NSCLC cells with TGF-beta 1 and PMA resulted in a persistent
      increase in the expression of fibronectin mRNA and protein. This response was
      blocked by the addition of H7. Inhibition of these effects by H7 in NSCLC cells
      suggests that H7 blocks TGF-beta responses by inhibiting a protein
      serine/threonine kinase(s). Because the effects of TGF-beta and PMA on the
      different TGF-beta isoforms, PA, PAI and fibronectin in NHBE and NSCLC cells are
      complex, our data suggest that there are distinct mechanisms for controlling the
      different TGF-beta isoforms, PA, PAI and extracellular matrix proteins in normal
      lung and lung cancer cells.

PMID- 9255609
TI  - VEGF mRNA is stabilized by ras and tyrosine kinase oncogenes, as well as by UV
      radiation--evidence for divergent stabilization pathways.
AB  - Vascular Endothelial Growth Factor (VEGF) is a pivotal endothelial cell mitogen
      that mediates both normal and pathological angiogenesis. Although expressed at
      very low levels in cells not undergoing vascularization, VEGF mRNA is transiently
      upregulated and stabilized by a variety of extracellular stimuli, and is
      persistently upregulated and stabilized in many human tumor cell lines (White et
      al., 1995). Here we demonstrate that oncogenic activation of tyrosine protein
      kinases and Ras proteins induce a 6- to 16-fold increase in the abundance of VEGF
      mRNA and a 3- to 5-fold increase in the stability of VEGF mRNA, suggesting that
      persistent activation of signaling pathways induced by these oncoproteins
      accounts for overexpression of VEGF in a significant fraction of human tumors. In
      addition to these oncoproteins, ultraviolet (UV) radiation upregulated and
      stabilized VEGF mRNA 15- and 5-fold, respectively. While the tyrosine kinase
      inhibitor, genistein, blocked VEGF upregulation by activated tyrosine protein
      kinases, and the Ras inhibitor, N-Acetyl-S-trans-farnesyl-L-cysteine (AFC),
      eliminated VEGF expression in cells transformed by v-Ras, neither agent blocked
      upregulation by hypoxia or UV radiation. These data argue that multiple divergent
      pathways upregulate and stabilize VEGF mRNA.

PMID- 9255610
TI  - Hemoglobinopathies in Southeast Asia: molecular biology and clinical medicine.

PMID- 9255611
TI  - Hb Watts [alpha 74(EF3) or alpha 75(EF4)Asp-->0]: a shortened alpha chain variant
      due to the deletion of three nucleotides in exon 2 of the alpha 2-globin gene.
AB  - We have identified a new, slightly unstable alpha chain hemoglobin variant,
      present in a Mexican-American family. Amino acid sequencing and mass spectral
      analysis of the aberrant peptide (alpha T-9) of the variant revealed that the
      aspartic acid is deleted either at position 74 or 75 of one of the alpha-globin
      chains. Sequencing of the amplified alpha 2- or alpha 1-globin genes revealed a
      trinucleotide deletion (GAC) at codon 74 or 74 of the alpha 2 gene. Although the
      aspartic acid residues of 74 and 75 of the alpha chain are neither a heme nor an
      inter chain contact, the slight instability of Hb Watts may be due to disturbance
      of the central cavity of hemoglobin by the deletion of an aspartic acid residue
      in the EF helix. Hb Watts is the first example of a trinucleotide deletion in the
      alpha 2-globin gene.

PMID- 9255612
TI  - Hb Seal Rock [(alpha 2)142 term-->Glu, codon 142 TAA-->GAA]: an extended alpha
      chain variant associated with anemia, microcytosis, and alpha-thalassemia-2 (-3.7
      Kb).
AB  - Hb Seal Rock was first reported in a young African-American women and her 2-year
      old daughter (1). It is an extended alpha chain variant which, like Hb Constant
      Spring, is present in small quantity and is expressed as an alpha-thalassemia.
      The mutation, TAA-->GAA affects codon 142 of the alpha 2 gene. In this family,
      the index case was a compound heterozygote for Hb Seal Rock trait and for alpha
      thalassemia trait (-3.7 kb). Her hematologic expression was similar to mild Hb H
      disease, presumably because the Seal Rock mutation affects the alpha 2 gene that
      is normally responsible for approximately 70% of alpha-globin synthesis. Her
      daughter had only Hb Seal Rock trait, but was phenotypically alpha-thalassemia-2
      trait due to the expression of the Seal Rock mutation on one of her alpha 2
      globin genes, the other three alpha-globin genes being unaffected.

PMID- 9255613
TI  - A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gambara
      [beta 82(EF6)Lys-->Glu].
AB  - Hb Gambara is a new hemoglobin variant with abnormal beta chains that has been
      found in three out of four members of a family of Lombardy origin (Gambara,
      Brescia, Northern Italy). The affected subjects led a normal life, but they had
      modest erythrocytosis and mild (compensated) hemolysis with slight splenomegaly.
      Their abnormal hemoglobin was about 52% of the total hemoglobin, and was shown to
      be stable by the isopropanol test. Whole blood P50 of the proband was 19.3 Torr,
      Bohr effect was decreased (-0.25), as well as the molar ratio between the 2,3
      diphosphoglycerate level and total hemoglobin of erythrocytes (0.68). The
      purified abnormal hemoglobin was characterized by an altered oxygen affinity, low
      n-factor, chloride, and 2,3-diphosphoglycerate effects. The Bohr effect was about
      40% of the normal control. The abnormal hemoglobin moved faster than Hb A at
      alkaline electrophoresis, and split into two fractions, probably due to the
      formation of hybrid tetramers (alpha 2 beta A beta X). The reversed phase high
      performance liquid chromatogram from the tryptic digest of the aminoethylated
      abnormal beta chain subunits indicated the presence of an extra peptide, beta T
      9, 10, replacing the individual peptides beta T-9 and beta T-10. Finally, the
      proband's DNA, drawn from a suitable segment of the beta structural gene (exon
      2), revealed a nucleotide sequence carrying the heterozygous mutation AAG-->GAG
      at codon 82. This led to a Lys-->Glu substitution at position 82(EF6) of the beta
      chain.

PMID- 9255614
TI  - Hb Zengcheng [beta 114(G16)Leu-->Met] in a Cambodian family.

PMID- 9255615
TI  - Hb D-Punjab in the United Arab Emirates.

PMID- 9255616
TI  - Hb Geelong [beta 139(H17)Asn-->Asp] found in a Japanese male.

PMID- 9255617
TI  - Novel beta 0-thalassemia mutation in a Canadian woman of British descent (codons
      72/73, -AGTGA, +T).

PMID- 9255618
TI  - Immunology of hematopoietic stem cell transplantation: a brief review of its
      history.
AB  - The history of clinical marrow transplantation since 1968 is reviewed with an
      emphasis on immunological and immunogenetic aspects. The events leading to the
      creation of an international network of volunteer donor registries and the
      implementation of unrelated allogeneic marrow transplantation as a routine
      procedure are discussed. Current major issues which need to be resolved are
      addressed in order to set the stage for the topics covered in this volume of
      Immunological Reviews.

PMID- 9255619
TI  - From stem cells to lymphocytes: biology and transplantation.
AB  - We review the development of the hematopoietic system, focusing on the transition
      from hematopoietic stem cells (HSCs) to T cells. This includes the isolation of
      HSCs, and recent progress in understanding their ontogeny, homing properties, and
      differentiation. HSC transplantation is reviewed, including the kinetics of
      reconstitution, engraftment across histocompatibility barriers, the facilitation
      of allogeneic engraftment, and the mechanisms of graft rejection. We describe
      progress in understanding T-cell development in the bone marrow and thymus as
      well as the establishment of lymph nodes. Finally, the role of bcl-2 in
      regulating homeostasis in the hematopoietic system is discussed.

PMID- 9255620
TI  - Delineation of the human hematolymphoid system: potential applications of defined
      cell populations in cellular therapy.
AB  - Hematopoietic stem cells (HSC) have the capacity to reconstitute all the blood
      cells in the body. HSC are rare, representing on average 0.05% of the mononuclear
      cells present in healthy human bone marrow. Due to their capacity for self
      renewal and their pluripotent, long-term reconstituting potential, HSC are
      considered ideal for transplantation to reconstitute the hematopoietic system
      after treatment for various hematologic disorders or as a target for the delivery
      of therapeutic genes. Human HSC also have potential applications in restoring the
      immune system in autoimmune diseases and in the induction of tolerance for
      allogeneic solid organ transplantation. With the increased interest in human HSC
      for clinical applications, technology for the isolation of candidate HSC and
      knowledge of human hematopoiesis have been growing rapidly. In this article, we
      discuss the functional characterization of a human CD34+Thy-1+ HSC population
      which is essentially free of residual disease, our efforts to generate alternate
      monoclonal antibodies for the isolation of clinically useful stem or progenitor
      cell populations, and the identification of a novel lymphoid progenitor as part
      of an exploration towards defining progenitors with potential application as
      adjuncts to HSC-based cellular therapy.

PMID- 9255621
TI  - Development and function of T lymphocytes and natural killer cells after bone
      marrow transplantation of severely immunodeficient mice.
AB  - Bone marrow (BM) transplantation experiments were performed in a strain of CD3
      epsilon-transgenic mice, termed tg epsilon 26, which are completely deficient in
      T-cell and natural killer (NK) cell development. We found that an interaction of
      stromal cells and prothymocytes is required for the induction of a cortical
      thymic microenvironment. This induction takes place in a time window from fetal
      development to early neonates. Although the thymic environment is not required
      for NK-cell development, we found that aberrantly educated alpha beta or gamma
      delta T lymphocytes can influence NK-cell ontogeny. Surprisingly, BM
      transplantation of tg epsilon 26 fetuses and neonates results in normal T-cell
      development, but very low levels of NK cells. The poor NK-cell reconstitution in
      fetal and neonatal stages could be explained by an inefficient migration of
      hematopoietic progenitor cells to the BM. By contrast, migration of the
      progenitor cells to the thymus was efficient to initiate T-cell development. BM
      transplantation of adult tg epsilon 26 mice resulted in abnormal T-cell
      development which, in turn, caused an inflammatory bowel disease (IBD) in the
      recipient mice. Studies in these BM chimeras have revealed that both alpha beta
      and gamma delta T cells can be pathogenic and, further, that Th1-like cytokines
      produced by these cells are causal factors in the pathogenesis of IBD.

PMID- 9255622
TI  - Pathways of T-cell regeneration in mice and humans: implications for bone marrow
      transplantation and immunotherapy.
AB  - Much of our understanding of the immunobiology of bone marrow transplantation
      (BMT) has come from studies in young adult mice reconstituted with T-cell
      depleted bone marrow after lethal irradiation. Recent evidence indicates,
      however, that the applicability of conclusions drawn from this model to human BMT
      may be limited. While mice retain essentially normal thymic function well past
      sexual maturity, humans show significant age-related declines in thymic function
      relatively early in life. Therefore, thymic-deficient mice may provide a more
      accurate model for study of the immunobiology of BMT. T-cell regeneration in
      thymic-deficient mice occurs primarily via antigen-driven expansion of mature
      peripheral T cells resulting in limited immune competence due to quantitative
      deficiencies in T-cell number and severe restriction in the diversity of the
      regenerated T-cell receptor (TCR) repertoire. Similarly, immune reconstitution in
      adult humans after BMT is marked by quantitative T-cell deficiencies, especially
      in the CD4+ subset, and loss of TCR diversity. Taken together, prevailing
      evidence suggests that thymic function is suboptimal in most BMT recipients, and
      that thymic-independent pathways of T-cell regeneration are generally limited in
      their ability to restore host immune competence. New strategies to enhance thymic
      function in man after BMT would hold great therapeutic potential.

PMID- 9255623
TI  - Immunological reconstitution following bone marrow transplantation.
AB  - The recipients of hematopoietic stem cell transplants are characterized by an
      immunodeficiency of varying severity and duration. Their immunoincompetence is
      due in part to: 1) a lack of sustained transfer of donor immunity, 2) a
      recapitulation of lymphoid ontogeny, 3) the effects of graft-versus-host disease
      and its therapy, and 4) a reduction in thymic function. Recipients can have
      delays in the production of naive T lymphocytes following transplantation which
      result in defects in the production of new antigen-specific T lymphocytes and an
      inability to produce antibodies, especially to carbohydrate antigens.

PMID- 9255624
TI  - Recent advances in graft-versus-host disease (GVHD) prevention.
AB  - In the 1970s and 1980s, GVHD prevention approaches were limited in number. Recent
      advances in our understanding of the requirements for T-cell immune responses and
      for basic mechanism(s) involved in GVHD pathophysiology have led to exciting new
      strategies for GVHD prevention. This review focuses upon recent developments in
      GVHD prevention generated over the past 5 years. We have selected five different
      types of strategies to highlight including: 1) the in vivo targeting of GVHD
      reactive T cells using either intact and F(ab')2 fragments of monoclonal
      antibodies directed against T-cell-surface determinants or immunotoxins which
      consist of antibodies linked to toxins, 2) a comparison of the in vivo
      immunosuppressive effects of FK506 and rapamycin on T-cell signaling, 3) the
      inhibition of T-cell activation through blockade of costimulatory or adhesogenic
      signals, 4) shifting the balance between acute GVHD-inducing T-helper-type 1
      (Th1) T cells to anti-inflammatory T-helper-type 2 (Th2)-type T cells, and 5) the
      regulation of alloreactive T-cell activation by treatment with peptide analogs
      which affect either TCR/MHC, CD4/MHC class II, or CD8/MHC class I interactions.
      Collectively, these approaches are illustratrative of the progress made in
      extending our GVHD prevention armamentarium.

PMID- 9255625
TI  - Immunobiology and immunotherapeutic implications of syngeneic/autologous graft
      versus-host disease.
AB  - Administration of the immunosuppressive drug cyclosporine (CsA) after
      syngeneic/autologous bone marrow transplantation (BMT) elicits an autoimmune
      syndrome with pathology virtually identical to graft-vs-host disease (GVHD). The
      induction of this syndrome, termed syngeneic/autologous GVHD, is a two-tiered
      process requiring both the active inhibition of thymic-dependent clonal deletion
      and the elimination of mature T cells that have an immunoregulatory effect.
      Eradication of the peripheral immunoregulatory compartment by the preparative
      regimen provides a permissive environment for the activation of the
      syngeneic/autologous GVHD effector T cells. Although the repertoire of
      autoreactive effector T lymphocytes is highly conserved, these T cells
      promiscuously recognize MHC class II determinants. This novel specificity of the
      autoreactive lymphocytes appears to be dependent on the peptide derived from the
      MHC class II invariant chain. Recent studies also suggest that these promiscuous
      autoreactive T cells can effectively target and eliminate MHC class II-expressing
      tumor cells. Administration of cytokines that upregulate the target antigen or
      expand the effector population can potentiate the antitumor activity of
      syngeneic/autologous GVHD. Although the induction of syngeneic/autologous GVHD is
      an untoward effect of CsA immunosuppression, mobilization of these autoimmune
      mechanisms provides a promising immunotherapeutic approach for certain neoplastic
      diseases.

PMID- 9255626
TI  - Human minor histocompatibility antigens: new concepts for marrow transplantation
      and adoptive immunotherapy.
AB  - Bone marrow transplantation (BMT) is the present treatment for hematological
      malignancies. Two major drawbacks of allogeneic BMT are graft-versus-host disease
      (GVHD) and leukemia relapse. The use of HLA-matched siblings as marrow donors
      results in the best transplant outcome. Nonetheless, the results of clinical BMT
      reveal that the selection of MHC-identical donors' bone marrow (BM) is no
      guarantee for avoiding GVHD or ensuring disease-free survival even when donor and
      recipient are closely related. It is believed that non-MHC-encoded so-called
      minor histocompatibility antigens (mHag) are involved in both graft-versus-host
      and graft-versus-leukemia activities. The recent new insights into the chemical
      nature of mHag not only reveal their physiological function but, more
      importantly, provide insights into their role in BMT. Together with the
      information on the human mHag genetics and tissue distribution gathered in the
      past, we may now apply this knowledge to the benefit of human BMT. Directly
      relevant is the utility of mHag molecular typing for diagnostics in BM donor
      selection. Most promising is the use of mHag-specific cytotoxic T cells for
      adoptive immunotherapy of leukemia.

PMID- 9255627
TI  - Hematopoietic stem cell transplants from unrelated donors.
AB  - Transplantation of hematopoietic stem cells is now well established as life
      saving therapy for patients with several different genetic and acquired diseases.
      This has been possible largely because of the identification of HLA as the human
      major histocompatibility system and the application of new technologies for
      improving the accuracy of HLA typing and matching. Clinical advances including
      the development of more effective immune suppression therapy and improvements in
      supportive care have also been critically important. The lack of HLA-identical
      sibling donors for most patients and the extensive polymorphism of HLA genes have
      necessitated establishing very large registries of HLA-typed volunteers. With
      more than 3 million donors now available worldwide, the number of patients
      identifying HLA matches has increased substantially. Despite a higher incidence
      of graft-versus-host disease (GVHD), the results of unrelated donor transplants
      are favorable when performed under optimal conditions with a well-matched donor.
      In order to provide transplants for all patients, improved methods for GVHD
      prophylaxis are needed that will make it possible to safely perform transplants
      even across limited degrees of HLA disparity.

PMID- 9255628
TI  - Factors influencing the outcome of bone marrow transplants using unrelated
      donors.
AB  - The use of unrelated donors for bone marrow transplantation (BMT) is associated
      with an increased morbidity and mortality when compared with HLA-identical
      donors, primarily due to an increased rate of graft-versus-host disease, but also
      to increased susceptibility to infections and graft failure. HLA matching for
      donors and recipients is the single most important factor influencing the outcome
      of BMT. However, unrelated donor selection generally relies on matching only for
      HLA-A, -B and -DR antigens without considering potential incompatibility for
      other HLA loci, such as HLA-C, -DQ and -DP. In addition, other factors that
      affect the outcome of BMT need to be taken into consideration in selecting the
      best unrelated donor. In this review, we will focus on the effects of HLA
      associated factors in determining the result of a transplant procedure. We will
      also mention other relevant factors, drawing on our experience of laboratory
      studies performed at The Anthony Nolan Research Institute and clinical studies at
      the Hammersmith Hospital in London.

PMID- 9255629
TI  - The potential role of NK cells in the separation of graft-versus-tumor effects
      from graft-versus-host disease after allogeneic bone marrow transplantation.
AB  - Allogeneic bone marrow transplantation (BMT) is being increasingly used for the
      treatment of a variety of cancers ranging from leukemias to breast cancer.
      However, significant obstacles currently limit the efficacy of this treatment
      procedure. The predominant two are the occurrence of graft-versus-host disease
      (GVHD) and relapse from the cancer. While regimens exist that prevent the
      occurrence or severity of GVHD, these same regimens also increase the rate of
      relapse. Conversely, most attempts to reduce the relapse rate also result in
      increased GVHD. The use of NK cells as an adoptive immunotherapy after BMT is
      attractive for several reasons. NK cells exhibit antitumor effects both in vitro
      and in animal models and may, therefore, promote graft-versus-tumor (GVT) effects
      to remove minimal residual disease after allogeneic BMT. NK cells have also been
      shown to promote hematopoietic engraftment and donor cell reconstitution after
      allogeneic BMT in mice. The effects of NK cells on hematopoiesis are believed to
      be due to the hematopoietic growth factors they can produce after activation.
      Another advantage in using NK cells is that they can prevent the occurrence of
      GVHD after allogeneic BMT in mice. This effect is mediated at least in part by
      the immunosuppressive cytokine, transforming growth factor beta (TGF-beta). BMT
      studies in mice also indicate that the beneficial effects of NK cells are optimal
      if they are administered soon after the transplant. Thereafter, NK cells and,
      more importantly, IL-2, which is used to activate them, are detrimental and can
      exacerbate the subsequent GVHD. Thus, the use of activated NK cells after
      allogeneic BMT may provide GVT effects without inducing GVHD.

PMID- 9255630
TI  - Therapy with cultured T cells: principles revisited.
AB  - In animals and in humans, T-cell therapy can cure advanced disseminated leukemia
      that would otherwise be fatal. The therapeutic effect of immune T cells is
      quantitative. As the dose of effector T cells is increased, survival is
      proportionately increased. Therefore, effective T-cell therapy is predicated on
      the ability to procure large numbers of immune effector T cells. By using
      cultured T cells, the number of immune T cells can be increased in vivo
      substantially above the level achievable by vaccination. The survival of cultured
      T cells in vivo is dependent upon both the culture conditions used and the
      therapeutic regimens employed. Under appropriate conditions, cultured T cells can
      proliferate in vivo in response to stimulation by antigen, distribute widely and
      survive long term to provide effector function and immunologic memory. Given that
      T cells recognize peptides, the need for immunization with tumor can be
      circumvented by immunization with peptide. Peptide-specific T cells and the
      progeny of single T-cell clones can provide the necessary cellular functions to
      eradicate disseminated murine leukemia. The ability of cloned T cells to
      similarly provide substantial measurable immunity in humans has been validated in
      clinical trials. By priming with peptides and by using established culture
      conditions, T-cell therapy can now be directed against virtually any antigen
      within the host T-cell repertoire. The major remaining question to be answered is
      which proteins and which peptides are the most suitable targets for T-cell
      therapy trials.

PMID- 9255631
TI  - Biology and adoptive cell therapy of Epstein-Barr virus-associated
      lymphoproliferative disorders in recipients of marrow allografts.
AB  - Epstein-Barr virus (EBV) is an ubiquitous herpesvirus which is carried as a
      latent infection of B lymphocytes and salivary gland epithelial cells in over 90%
      of normal adults. Latently infected EBV-transformed B cells circulate at low
      frequency in the blood for the life of the host. These transformed B cells
      stimulate a heterogeneous and complex host cell response, ultimately leading to
      the development and maintenance of high frequencies of HLA-restricted T cells
      specific for the EBV-encoded nuclear antigens EBNA2-EBNA6 and the latency
      membrane proteins LMP-1 and LMP-2. Responses to latent EBV-encoded proteins are
      hierarchical with responses to certain epitopes predominating, dependent upon the
      HLA genotype of the host. Profound suppression of T-cell immunity may permit the
      emergence of polyclonal, oligoclonal or monoclonal EBV antigen-expressing
      lymphoproliferative disorders or malignant B-cell lymphomas expressing these
      latent EBV antigens. Adoptive transfer of small numbers of peripheral blood
      mononuclear cells or HLA-partially matched T cells from in vitro expanded EBV
      specific T-cell lines derived from a seropositive marrow donor has induced
      durable regressions of bulky, widely metastatic monoclonal EBV lymphomas in a
      high proportion of cases. This review describes the current state of knowledge
      and hypothesis regarding the biology and immunology of EBV infection in the
      normal host, the features of donor, host and virus which contribute to the
      development of EBV-associated lymphoproliferative diseases and the mechanisms
      whereby they are controlled by adoptive transfer of immune T cells.

PMID- 9255632
TI  - Adoptive cellular immunotherapy for EBV lymphoproliferative disease.
AB  - Reactivation of EBV (Epstein-Barr virus) after bone marrow transplantation can
      result in EBV-associated lymphoproliferative disease (EBV-LPD). We have
      administered donor-derived EBV-specific cytotoxic T lymphocytes (CTL) to patients
      who are at high risk of this complication after receiving a T-cell-depleted
      allograft from a matched unrelated or mismatched related donor. The cells were
      marked with the neo gene before infusion so that we could evaluate their
      persistence and efficacy. CTL infusion produced a virus-specific immune response
      to EBV that persisted for up to 2 years. None of the 36 patients who received
      prophylactic CTLs have developed EBV-LPD, compared with a cumulative risk of 14%
      in patients who did not receive this treatment. Strong evidence of clinically
      valuable immune activity comes from 6 of these 36 patients whose pre-CTL levels
      of EBV DNA were elevated to a degree strongly predictive of the onset of
      lymphoma. In each of these cases, the levels returned to baseline after CTL
      infusion. 2 patients who were treated for clinically evident EBV-LPD attained
      prolonged remission after CTL infusion and in situ hybridization and
      semiquantitative PCR showed that the gene-marked CTL had selectively accumulated
      at disease sites. The prophylactic CTL treatment lacked acute adverse effects,
      whereas 1 patient who received CTLs for bulky established disease developed
      initial tumor swelling and respiratory obstruction. We conclude that EBV-specific
      CTLs are a safe and effective prophylaxis for EBV lymphoma and can also eradicate
      established disease. This approach is now being extended to other viruses that
      produce post-transplant morbidity and to other EBV-associated malignancies.

PMID- 9255633
TI  - Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia.
AB  - In addition to chemotherapy and irradiation, in the context of allogeneic stem
      cell transplantation (SCT), the donor cell-mediated antileukemic effect can lead
      to sustained complete remissions, also in cases of a large tumor load. This
      phenomenon appears to be an immunologically mediated response, possibly due to
      various effector cell populations. Cytotoxic T-lymphocyte (CTL) responses against
      minor histocompatibility antigens with restricted tissue distribution, in
      particular restricted to some or all hematopoietic cells, may be highly efficient
      in inducing anti-leukemic responses for adoptive immunotherapy. Specific CTL
      responses against leukemia-associated antigens may be generated using leukemic
      cells modified to coexpress costimulatory molecules identical to professional
      antigen-presenting cells. Donor-derived T cells recognizing such antigens may be
      used in the context of allogeneic SCT to induce complete and sustained
      remissions, also in patients with leukemia refractory to chemotherapy. In these
      circumstances, the primary objective of allogeneic SCT may be not to diminish the
      number of malignant cells by the chemotherapy and irradiation as part of the
      conditioning regimen, but to allow immunotherapy against leukemic cells using
      donor lymphocyte populations.

PMID- 9255634
TI  - Cellular immunotherapy and autologous transplantation for hematologic malignancy.
AB  - The success of allogeneic transplantation is in part due to the immunotherapeutic
      effect mediated by the graft. Autologous transplantation is hampered by the
      absence of this effect, leading to a higher relapse rate. We have conducted a
      series of studies designed to augment the immunologic activity of the graft after
      autologous transplant with a view towards introducing an autologous graft-versus
      tumor effect that could decrease the rate of relapse after autologous transplant.
      These studies have included IL-2 activation of marrow followed by post-transplant
      infusional IL-2, the development of a novel protocol for the generation of highly
      efficient cytotoxic effector cells, termed cytokine-induced killer (CIK) cells,
      with broad and potent antitumor activity. In order to determine the potential for
      generating peptide-specific cytolytic T cells, studies have been conducted upon
      transducing antigen-presenting cells (APC) with AAV vector-mediated gene
      transfer, a vector capable of transducing non-proliferating target cells.
      Transduction of human monocytes and macrophages resulted in high expression of
      the transduced gene. This latter study forms the basis for determining whether
      genetic modification of APC can potentiate specific immune responses to tumor
      specific gene products. Taken together, these strategies will hopefully increase
      the therapeutic efficacy of autologous transplantation.

PMID- 9255635
TI  - Pa catheterization--quo vadis? Do we have to change the current practice with
      this monitoring device?

PMID- 9255636
TI  - Percutaneous dilatational tracheostomy: risks and benefits.

PMID- 9255638
TI  - The Therapeutic Intervention Scoring System: one single tool for the evaluation
      of workload, the work process and management?

PMID- 9255637
TI  - Is bleomycin-detectable iron present in the plasma of patients with sepsis
      syndrome?

PMID- 9255639
TI  - Cost accounting in ICUs: beneficial for management and research.

PMID- 9255640
TI  - The pathophysiology of pre-eclampsia.

PMID- 9255641
TI  - Percutaneous dilatational tracheostomy in a medical ICU.
AB  - OBJECTIVE: To evaluate the safety of percutaneous dilatational tracheostomy.
      DESIGN: A prospective clinical study. SETTING: The intensive care unit of a
      university medical clinic. PATIENTS: 137 critically ill patients admitted between
      May 1993 and September 1996. INTERVENTION: Percutaneous dilatational tracheostomy
      at the bedside. RESULTS: The median duration of translaryngeal intubation prior
      to tracheostomy was 8 days. Tracheostomy was carried out within 12.8 min (range 7
      30 min). Acute complications were documented in 11.0% of the patients. There was
      one case of severe bleeding with transient asphyxia. Four patients had tracheal
      mucosal laceration treated conservatively. The postoperative in-hospital
      complication rate was 5.1%, the sole problem being stomal bleeding. Only two
      cases of stomal infection were documented. There was no procedure-related
      mortality. CONCLUSION: In the hands of the experienced, percutaneous dilatational
      tracheostomy is a safe and quick bedside procedure. It is also less expensive and
      incurs minimal stress for the patient compared with the surgical method. The
      technique can be easily mastered by non-surgical physicians and we feel that it
      is the method of choice for elective tracheostomy in the majority of intensive
      care patients.

PMID- 9255642
TI  - Is bleomycin-detectable iron present in the plasma of patients with septic shock?
AB  - OBJECTIVE: To assess plasma iron status in critically ill patients with septic
      shock. DESIGN: Observational, prospective study. SETTING: Adult intensive care
      units in teaching and tertiary referral hospitals. PATIENTS AND PARTICIPANTS:
      Fifteen adult patients with established septic shock. Normal control subjects (n
      = 10) were also investigated. Data from patients and controls were compared with
      previously published iron values in critical care patients. MEASUREMENTS AND
      RESULTS: The indices investigated and correlated with clinical scores of illness
      severity included bleomycin-detectable iron, non-haem iron; transferrin and its
      percentage iron saturation, and the iron binding (anti-oxidant) activity of
      transferrin. Bleomycin-detectable iron was not present in the plasma of patients
      with septic shock whilst the plasma transferrin remained unsaturated with iron.
      One patient in multi-organ failure displayed bleomycin-detectable iron in plasma
      (1.16 mumol/l) and had 100% iron-saturation of transferrin. The plasma non-haem
      iron levels (7.84 +/- 1.82 mumol/l) were the lowest of all critical care patient
      groups studied by us. The plasma transferrin levels were also low but resulted in
      a near normal percentage saturation of transferrin with iron (34.6 +/- 6.5%). The
      scores of clinical severity correlated with changes in plasma iron chemistry.
      CONCLUSIONS: Patients with septic shock rarely have iron saturated transferrin in
      their plasma leading to the presence of bleomycin-detectable iron.

PMID- 9255643
TI  - Validation of the simplified therapeutic intervention scoring system on an
      independent database.
AB  - OBJECTIVE: To evaluate the performance of the Simplified Therapeutic Intervention
      Scoring System on an independent database and determine its relation with the
      Therapeutic Intervention Scoring System in the quantification of nursing workload
      in intensive care. DESIGN: Analysis of the database of a multicenter prospective
      Portuguese study. SETTING: 19 intensive care units (ICUs) in Portugal. PATIENTS:
      Data on 1094 patients consecutively admitted to the ICUs were collected during a
      period of 3 months. METHODS: Collection of the data necessary for the calculation
      of the Therapeutic Intervention Scoring System (TISS-76) and the Simplified
      Therapeutic Intervention Scoring System (TISS-28) during the first 24 h in the
      ICU. Basic demographic statistics and all the variables necessary for the
      computation of the Simplified Acute Physiology Score II were also collected.
      Vital status at discharge from the hospital was registered. Regression
      techniques, Pearson's correlation and paired sample t-test were used. Results are
      presented as mean +/- standard deviation except when stated otherwise.
      Reliability was evaluated by the use of intraclass correlation coefficients in a
      5% random sample. MEASUREMENTS AND RESULTS: After exclusion of all the patients
      with missing data, 1080 patients were analysed. The overall mean TISS-28 (29.82
      +/- 10.64) was significantly lower than the mean TISS-76 (31.14 +/- 11.95). Both
      systems showed very significant differences between ICUs (p < 0.001). The
      correlation between the two was good, with TISS-28 explaining 72% of the
      variation of TISS-76 (r = 0.85, r2 = 0.72). The relation between the two systems
      was TISS-28 = 6.22 + 0.85 TISS-76. In this cohort, reliability of data collection
      was very high, with intraclass correlation coefficients greater than 0.90 for
      both systems. CONCLUSIONS: TISS-28 was validated on this independent population.
      The results indicate that TISS-28 can replace TISS-76 for the measurement of the
      nursing workload in Portuguese ICUs.

PMID- 9255644
TI  - A new method of accurately identifying costs of individual patients in intensive
      care: the initial results.
AB  - OBJECTIVES: To analyse the patient-related and non-patient-related costs of
      intensive care using an activity-based costing methodology. DESIGN: A
      retrospective cost analysis of 68 patients admitted sequentially over a 10-week
      period. SETTING: The Adult General Intensive Care Unit of the Royal Hallamshire
      Hospital, Sheffield. RESULTS: The results showed large variations in the costs
      obtained for individual patients. The calculation of the costs for the initial
      period of stay showed a wide variation depending on whether the costs were
      determined per calendar day or per first 24-h period. Significant correlations of
      costs between the first 24 h of stay and the admitting Acute Physiology and
      Chronic Health II score (p < 0.004) and daily costs with the Therapeutic
      Intervention Scoring System scores (p < 0.0001) were found. The average daily
      patient-related cost of care was Pounds 592. Overhead costs were calculated at
      Pounds 560 per patient day, which made the total cost of a day's treatment in
      intensive care Pounds 1152. CONCLUSIONS: The use of average costs or scoring
      systems to cost intensive care is limited, as these methods cannot determine
      actual resource usage in individual patients. The methodology described here
      allows all the resources used by an individual patient or group of patients to be
      identified and thus provides a valuable tool for economic evaluations of
      different treatment modalities.

PMID- 9255645
TI  - New monitors of intravascular volume: a comparison of arterial pressure waveform
      analysis and the intrathoracic blood volume.
AB  - OBJECTIVE: Two new monitoring techniques, the analysis of arterial pressure
      waveform during mechanical ventilation and the determination of intrathoracic
      blood volume, were evaluated for preload assessment in a model of graded
      hemorrhage. DESIGN: 8 anesthetized dogs bled of 10, 20, and 30% of their blood
      volume, then retransfused and volume loaded with plasma expander. Central venous
      pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output,
      parameters of the arterial pressure waveform analysis [systolic pressure
      variation (SPV) and delta down (dDOWN)], and intrathoracic blood volume (ITBV)
      were measured at baseline and after each stage of hemorrhage and volume
      expansion. RESULTS: The stroke volume index decreased significantly from 1.3 +/-
      0.4 ml/kg at baseline to 0.7 +/- 0.2 ml/kg at 30% hemorrhage and then increased
      after retransfusion and volume loading. The changes in the filling pressures
      during the various stages of hemorrhage were in the range of 1-2 mmHg. CVP
      decreased from 5.5 +/- 0.9 to 3.1 +/- 1.7 mmHg and PCWP from 8.0 +/- 0.8 to 5.1
      +/- 1.2 mmHg at 30% hemorrhage. Both filling pressures responded significantly to
      retransfusion; PCWP also changed in response to a volume load. SPV and dDOWN
      (expressed as percent of the systolic blood pressure during a short apnea)
      increased significantly from 6.7 +/- 1.7 and 5.6 +/- 3.2%, respectively, at
      baseline, to 9.7 +/- 2.6 and 8.1 +/- 2.9% after 10% blood loss and to 13.1 +/-
      3.9 and 11.1 +/- 3.8% after 30% hemorrhage. ITBV decreased significantly from
      29.7 +/- 4.5 to 26.8 +/- 5.3 ml/kg after 10% blood loss and to 23.1 +/- 3.0 ml/kg
      after 30% hemorrhage. ITBV, SPV, and dDOWN responded significantly to
      retransfusion and volume load. Significant correlations were found between the
      degree of volume change and dDOWN (r = 0.93), SPV (r = 0.96), ITBV (r = 0.95),
      CVP (r = 0.82), and PCWP (r = 0.90). CONCLUSIONS: The parameters of arterial
      pressure waveform analysis (SPV and dDOWN) and ITBV were sensitive estimates of
      cardiac preload during the early stages of hemorrhage. Measurement of SPV and
      dDOWN, being both sensitive and relatively noninvasive, has advantages over other
      methods of preload assessment but is limited to patients on controlled mechanical
      ventilation. ITBV, which supplies quantitative information about cardiac preload,
      is more invasive but can also be used in patients who are breathing spontaneously
      or who are on partial ventilatory support.

PMID- 9255646
TI  - Type of solution and PCO2 measurement errors during tonometry.
AB  - OBJECTIVE: The choice of solution for gastrointestinal tonometry influences the
      PCO2 measurement bias, precision and the time required for equilibration. We
      compared saline with buffered solutions during in vitro tonometry, with respect
      to systematic and accidental measurement errors and equilibration time. DESIGN: A
      prospective laboratory study. MEASUREMENTS: Saline, phosphate, phosphate
      bicarbonate and succinylated gelatin solutions were equilibrated in a specialized
      blood gas tonometer at PCO2s of 2.7, 3.6, 4.5, 6.2 and 9.0 kPa, using calibration
      gases. Accidental errors were determined: the within-syringe decline of PCO2 and
      the effects of handling errors (five up and down movements of the plunger). The
      PCO2 build up in gastrointestinal tonometers was determined in 5000 ml saline
      baths with fixed PCO2 levels of 2.7 and 9.0 kPa. RESULTS: The build up of PCO2 in
      phosphate bicarbonate and gelatin was about 4 and 2 times slower than in saline
      and phosphate, respectively, both for gas and gastrointestinal tonometers. The
      bias of the measured PCO2 at equilibrium was -15% for saline, and between -1 and
      3% for phosphate, phosphate bicarbonate and gelatin. The precision was comparable
      among the solutions: 2 +/- 1% for saline, 2 +/- 1% for phosphate, 1 +/- 0% for
      phosphate bicarbonate and 1 +/- 1% for gelatin. The accidental errors were
      virtually absent with phosphate bicarbonate, intermediate with gelatin and
      largest with saline and phosphate. CONCLUSION: Phosphate bicarbonate buffer and
      succinylated gelatin allow accurate PCO2 measurements, but their equilibration is
      too slow for clinical application. The advantage of phosphate over saline
      solution is a smaller bias only. Thus, both saline and phosphate are currently
      the tonometer solutions of choice, provided that strictly anaerobic conditions
      are applied and the bias by the blood gas analyzer is known.

PMID- 9255647
TI  - Effects of epinephrine on right ventricular function in patients with severe
      septic shock and right ventricular failure: a preliminary descriptive study.
AB  - OBJECTIVE: To recognize patients with unresponsive septic shock and right
      ventricular (RV) failure and to evaluate the effects of epinephrine on RV
      performance in these patients. DESIGN: Prospective descriptive study. SETTING:
      Medical intensive care unit. SUBJECTS: 14 consecutive patients in septic shock
      unresponsive to fluid loading, dopamine, and dobutamine. INTERVENTIONS:
      Evaluation of RV function by thermodilution with a pulmonary artery catheter
      equipped with a rapid-response thermistor. Measurements were obtained before and
      during epinephrine infusion to achieve a systolic arterial pressure > or = 90
      mmHg or a mean arterial pressure (MAP) > or = 70 mmHg. RESULTS: At the time of
      inclusion in the study the hemodynamic pattern in the 14 patients was as follows:
      (MAP) 58 +/- 14 mmHg, systemic vascular resistance (SVR) 1046 +/- 437 dyne.s.cm
      5.m-2, pulmonary artery occlusion pressure (PAOP) 14 +/- 4 mmHg, mean pulmonary
      artery pressure (MPAP) 24 +/- 4 mmHg, right arterial pressure (RAP) 11 +/- 4
      mmHg, cardiac index (CI) 4 +/- 1.7 l/min per m2. During epinephrine infusion,
      MAP, CI and stroke volume index (SVI) were increased (27%, p < 0.01; 20%, p <
      0.01; 15%, p < 0.05, respectively). There was no change in PAOP, SVR or heart
      rate. Seven patients (group A) had marked RV failure defined by both RV dilation
      [RV end-diastolic volume index (RVEDVI) > 92 ml/m2] and low RV ejection factor
      (RVEF) (< 52%) and 7 did not (group B). Group A had a lower baseline RVEF than
      group B (24 +/- 7 vs 45 +/- 9%, p < 0.05), a higher RVEDVI (134 +/- 28 vs 79 +/-
      17 ml/ m2, p < 0.01), and a higher RVES (systolic) VI (103 +/- 30 vs 43 +/- 11
      ml/ m2, p < 0.01). The other hemodynamics, especially RAP and RV stroke work
      index (RVSWI) were no different in the two groups and did not predict RV
      dysfunction. In group A, epinephrine infusion improved RVEF (25%, p < 0.05) by a
      reduction in RVESVI (-8%, p < 0.05) without any change in RVEDVI or in RAP, in
      spite of a rise in MPAP (11%, p < 0.05). A rise in RVSWI (76%, p < 0.05), SVI
      (23%, p < 0.05), and CI (24%, p < 0.05) was also achieved. An upward vertical
      shift of the Frank-Starling relationship RVSWI/ RVEDVI and an upward shift to the
      left of the pressure volume relationship pulmonary artery peak pressure/RVESVI
      was observed only in the group with RV failure following treatment with
      epinephrine. In group B (without RV failure), RV parameters were not modified by
      epinephrine. CONCLUSION: In patients with severe septic shock, RV dysfunction was
      identified by the use of an RVEF pulmonary artery catheter and was improved by
      epinephrine by means of an improvement in RV contractility.

PMID- 9255648
TI  - Effects of high-frequency oscillatory ventilation on circulation in neonates with
      pulmonary interstitial emphysema or RDS.
AB  - OBJECTIVE: Mechanical ventilation may impair cardiovascular function if the
      transpulmonary pressure rises. Studies on the effects of high-frequency
      oscillatory ventilation (HFOV) on cardiovascular functions have yielded
      conflicting results. This study was done to compare alterations in left
      ventricular output and blood flow velocities in the anterior cerebral artery,
      internal carotid artery, and celiac artery using a Doppler ultrasound device
      before and 2 h after initiating HFOV in neonates with respiratory distress
      syndrome (RDS) or pulmonary interstitial emphysema (PIE). DESIGN: Prospective
      clinical study. SETTING: Neonatal intensive care unit in a perinatal center.
      PATIENTS: 18 critically ill infants (postnatal age 47 +/- 12 h; mean +/- SD) were
      studied before and during HFOV (piston oscillator). Indications for HFOV were
      severe respiratory failure due to PIE (n = 10) and severe surfactant deficiency
      (RDS, n = 8). In the RDS group, gestational age was 27 +/- 6 weeks (range 26-31
      weeks) and birth-weight 1620 +/- 380 g (range 850-1970 g). In the PIE group,
      gestational age was 28 +/- 2 weeks (range 26-36 weeks) and birth-weight 1740 +/-
      470 g (range 890-2760 g). MEASUREMENTS AND MAIN RESULTS: During HFOV, mean airway
      pressure was maintained at the same level as during intermittent mandatory
      ventilation in both groups (RDS, 12 +/- 2 cmH2O; PIE, 10 +/- 2 cmH2O). Compared
      to intermittent mandatory ventilation, several of the 12 parameters studied
      changed significantly (p < 0.004) during HFOV. In the RDS group, the partial
      pressure of oxygen in arterial blood/fractional inspired oxygen (PaO2/FIO2) ratio
      increased from 56 +/- 9 to 86 +/- 7 and partial pressure of carbon dioxide in
      arterial blood (PaCO2) decreased from 49 +/- 4 to 35 +/- 3 mmHg. In the PIE
      group, PaO2/FIO2 ratio increased from 63 +/- 8 to 72 +/- 7 and PaCO2 decreased
      from 63 +/- 7 to 40 +/- 5 mmHg. In the PIE group, heart rate decreased (135 +/-
      15 before HFOV vs 115 +/- 14 min-1 during HFOV) and mean systolic blood pressure
      increased (before 43 +/- 4 vs 51 +/- 4 mmHg during HFOV) significantly, whereas
      these parameters did not change in the RDS group. Left ventricular output
      increased significantly in the PIE group (210 +/- 34 before vs 245 +/- 36 ml/kg
      per min during HFOV; p < 0.004), but not in the RDS group (225 +/- 46 before vs
      248 +/- 47 ml/kg per min during HFOV; k < 0.05). Shortening fraction and systemic
      resistance did not change in either group. In the PIE group, mean blood flow
      velocities in the internal carotid artery (+59%), anterior cerebral artery (+65%)
      and celiac artery (+45%) increased significantly but did not change in the RDS
      group. CONCLUSIONS: The results show that HFOV as used in this study, improves
      oxygenation, CO2 elimination, and circulation in infants with RDS and PIE.
      However, systemic, cerebral, and intestinal circulation improved more in neonates
      with PIE than in those with RDS. This may be due to higher pulmonary compliance
      in infants with PIE when compared to those with RDS.

PMID- 9255649
TI  - Urea removal by neonatal hemo(dia)filters in hyperazotemic rabbits.
AB  - OBJECTIVE: Comparison of three neonatal hemo(dia)filters (FH22, Gambro;
      Minifilter Plus, Amicon; Miniflow 10, Hospal) for removal of urea by venovenous
      hemofiltration (HF) and venovenous hemodiafiltration (HDF). DESIGN: Filters were
      successively used for HF with two different blood flows (Qb = 8.3 and 16.6 ml/
      min) and for HDF with the two different blood flows and four dialysate flows (Qd
      = 0.5, 1.0, 2.0, and 3.0 l/h). SUBJECTS: 21 anesthetized adult New Zealand White
      rabbits infused with urea. MAIN RESULTS: Urea clearance was significantly
      increased by HDF compared to HF regardless of blood flow, dialysate flow, and the
      hemo (dia)filter type except in the FH22 group, when blood flow was high and
      dialysate flow was 0.5 or 1.0 l/h. The FH22 filter allowed the best urea
      clearance during HF at high blood flow. During the HDF procedures, the Miniflow
      10 allowed the highest urea clearance regardless of blood flow and dialysate
      flow.

PMID- 9255650
TI  - Predictors of mortality and multiple organ failure in children with sepsis.
AB  - OBJECTIVES: To assess the markers of perfusion which best discriminate survivors
      from non-survivors of childhood sepsis and to compare the information derived
      from gastric tonometry with conventionally measured haemodynamic and laboratory
      parameters. DESIGN: Prospective clinical study of children with sepsis syndrome
      or septic shock. SETTING: Paediatric intensive care unit in a tertiary referral
      centre. PATIENTS: 31 children with sepsis syndrome or septic shock.
      INTERVENTIONS: A tonometer was passed into the stomach via the orogastric route.
      MEASUREMENTS AND MAIN RESULTS: The following data were recorded at admission, 12,
      24 and 48 h: heart rate, mean arterial pressure, arterial pH, base deficit,
      arterial lactate, gastric intramucosal pH (pHi) and DCO2 (intramucosal carbon
      dioxide tension minus arterial partial pressure of carbon dioxide). The principal
      outcome measure was. The secondary outcome measure was the number of organ
      systems failing at 48 h after admission. There were 10 deaths and 21 survivors.
      No variable discriminated survival from death at presentation. Blood lactate
      level was the earliest discriminator of survival. Using univariate logistic
      regression, lactate discriminated survivors from those who died at 12 and 24 h
      after admission, but not at 48 h (p = 0.049, 0.044 and 0.062, respectively). The
      area under the receiver operating characteristic (ROC) curve for lactate was
      0.81, 0.88 and 0.89 at 12, 24 and 48 h, respectively. At 12 h after admission, a
      blood lactate level > 3 mmol/l had a positive predictive value for death of 56%
      and a lactate level of 3 mmol/l or less had a positive predictive value for
      survival of 84%. At 24 h a lactate level > 3 mmol/l had a positive predictive
      value for death of 71% and a level of 3 mmol/l or less had a positive predictive
      value for survival of 86%. No other variable identified non-survivors from
      survivors at 12 h. Gastric tonometry could only be done on 19 of the 31 children,
      of whom 8 died and 11 survived. In these 19 children, DCO2 measured at 24 h, but
      not at 12 or 48 h, distinguished those who died from those who survived (p =
      0.045 and p = 0.20, respectively). The area under the ROC curve for DCO2 measured
      at 24 h as a predictor of survival was 0.71. Neither the absolute value of pHi
      nor the trend of change in pHi at any time in the first 48 h identified survivors
      in this series. The mean arterial pressure distinguished survivors from non
      survivors at 24 and 48 h (area under ROC curve = 0.80 and 0.78, respectively).
      The base deficit and heart rate did not identify non-survivors from survivors at
      any time in the first 48 h. CONCLUSIONS: Blood lactate level was the earliest
      predictor of outcome in children with sepsis. In this group of patients, gastric
      tonometry added little to the clinical information that could be derived more
      simply by other means.

PMID- 9255651
TI  - Intermittent administration of furosemide versus continuous infusion in the
      postoperative management of children following open heart surgery.
AB  - OBJECTIVE: To compare the amount of furosemide needed to fulfil defined criteria
      for renal output if given intermittently or as a continuous infusion and to
      compare the effect of these two regimens on hemodynamic variables and urine
      electrolyte concentrations. DESIGN: Prospective randomized study of postoperative
      hemodynamically stable pediatric cardiac patients. The patients were given
      furosemide according to the urine output, either as an intermittent bolus
      injection or as a continuous infusion. SETTING: Pediatric intensive care unit in
      a university hospital. PATIENTS: The patients were randomly assigned before
      admission to either the intermittent i.v. or the continuous furosemide i.v.
      infusion group. MEASUREMENTS AND RESULTS: Demographic and hemodynamic data were
      recorded for a maximum of 72 h, as were furosemide dose, urine output, and fluid
      and inotropic drug requirements. Forty-six patients completed the study. Maximal
      hourly urine output was significantly higher in the intermittent group. A
      significantly lower dose of furosemide in the intermittent group produced the
      same 24-h urine volume as in the continuous infusion group. CONCLUSIONS:
      Intermittent furosemide administration may be recommended in hemodynamically
      stable postoperative pediatric cardiac patients because of less drug requirement.
      However, the high maximal urine output may cause hemodynamic problems in patients
      who depend on high inotropic support.

PMID- 9255652
TI  - Shock complicating severe falciparum malaria in European adults.
AB  - OBJECTIVE: To study adult patients with severe falciparum malaria who developed
      shock. DESIGN: Retrospective study from 1987 to 1993. SETTING: Medical intensive
      care unit in a university hospital. PATIENTS: 14 patients admitted with severe
      falciparum malaria who developed shock. All received intravenous quinine.
      MEASUREMENTS AND RESULTS: The mean Simplified Acute Physiology Score II was 59.5
      +/- 7.1; 2.6 +/- 0.4 criteria defining severe disease were present on admission
      in 12 patients; and initial parasitemia was 21 +/- 6%. Twelve patients received
      inotropic drugs. Pulmonary artery catheterization showed the following results in
      7 patients: mean arterial pressure 57 +/- 4 mmHg; pulmonary artery occlusion
      pressure 11 +/- 1 mmHg; cardiac index 5.5 +/- 0.91.min-1.m-2, and systemic
      vascular resistance index 783 +/- 122 dyne.s.cm-5.m-2. Seven patients had
      evidence of bacterial infection at the time of shock. Of the 7 deaths (50%), 5
      were due to shock, with documented bacterial infection in all patients and
      persistent parasitemia in 4. CONCLUSIONS: Shock complicating severe falciparum
      malaria in adults is associated with peripheral vasodilation and carries a poor
      prognosis. In falciparum malaria with shock, bacterial coinfection should be
      suspected immediately and treated empirically with broad-spectrum antibiotics.
      Nevertheless, Plasmodium falciparum may contribute directly or indirectly to the
      onset of shock.

PMID- 9255653
TI  - Left-sided superior vena cava: diagnosis by magnetic resonance imaging.
AB  - We describe a case of left-sided superior vena cava. The diagnosis was suggested
      by chest radiograph after central venous catheter placement. This was
      subsequently confirmed by magnetic resonance imaging.

PMID- 9255654
TI  - Drawover vaporizers for sedation in intensive care.
AB  - OBJECTIVE: We have undertaken a laboratory study to determine whether a drawover
      vaporizer in the inspiratory limb of an intensive care ventilator circuit can
      produce safe and therapeutic concentrations of isoflurane. DESIGN: An Oxford
      Miniature Vaporizer (OMV) and Ohmeda TEC vaporizer were assessed over the range
      of inspired isoflurane concentrations, airway pressures and tidal volumes
      experienced in the ICU. CONCLUSIONS: The experimental findings suggest that the
      OMV inhaler in plenum mode can be relied upon to produce safe concentrations of
      isoflurane over a clinically useful range of inspired concentrations.
      Furthermore, it behaves predictably over the range of airway pressures likely to
      be encountered in the patient admitted with acute severe asthma. However, we
      found that the Ohmeda TEC vaporizer did not perform reliably in this setting.

PMID- 9255655
TI  - Circulatory shock in the course of fatal poisoning by ingestion of formalin.

PMID- 9255656
TI  - Puumala type hantavirus infection with early choleriform syndrome and severe
      multiorgan failure.

PMID- 9255657
TI  - A more differentiated classification of hydroxyethyl starches is necessary.

PMID- 9255659
TI  - The effect of case mix adjustment on mortality as predicted by APACHE II.

PMID- 9255658
TI  - Nitric oxide production.

PMID- 9255660
TI  - Epidemiology and natural history of benign prostatic hyperplasia.

PMID- 9255661
TI  - Prognostic factors for renal cell carcinoma: a multivariate analysis of 320
      cases.
AB  - BACKGROUND: We performed a multivariate analysis of clinical variables in 320
      patients with renal cell carcinoma to identify important prognostic factors for
      long-term survival. METHODS: We retrospectively reviewed the medical records of
      320 patients who presented with renal cell carcinoma. Survival curves were
      calculated by the Kaplan-Meier method and statistical differences were determined
      by the log-rank test. Significant prognostic factors were evaluated by Cox's
      multivariate proportional hazard model. RESULTS: The median follow-up period was
      29 months. The overall survival rates at 1, 5, and 10 years were 90.0%, 77.6%,
      and 69.9%, respectively. Seventeen of the 19 prognostic factors evaluated were
      shown to be significant by the log-rank test: patient age, sex, performance
      status, body temperature, erythrocyte sedimentation rate (ESR), levels of
      hemoglobin, alpha 2-globulin, C-reactive protein, fibrinogen, immunosuppressive
      acidic protein (IAP), size or involvement of tumor (T classification), regional
      lymph node involvement (N classification), extent of metastasis (M
      classification), pathologic grade, tumor cell type, mode of tumor infiltration,
      and the modality of treatment (curative surgery). Among them, the body
      temperature, ESR, alpha 2-globulin, fibrinogen, IAP, and mode of tumor
      infiltration were excluded from multivariate analysis because of missing data.
      Curative surgery was also excluded because it is a treatment modality and
      different from the other variables which are clinical or pathologic
      characteristics. From the remaining 10 variables, multivariate analysis showed
      that age (P = 0.0389), N classification (P = 0.0289), and M classification (P <
      0.0001) were important and independent prognostic factors for long survival.
      CONCLUSION: This analysis showed that age, N classification, and M classification
      were the most important factors predicting long-term survival of patients with
      renal cell carcinoma.

PMID- 9255662
TI  - Endoscopic injection of collagen for the treatment of female urinary stress
      incontinence.
AB  - BACKGROUND: The objective of our study was to assess the efficacy and safety of
      glutaraldehyde cross-linked collagen injection in the treatment of female urinary
      stress incontinence. METHODS: We conducted a retrospective analysis of the
      records of 105 women who underwent collagen injection for urinary stress
      incontinence between March 1991 and April 1995. Preoperative assessment included
      uroflowmetry, residual urine determination, and urodynamic studies. RESULTS: Of
      the 105 women in our series, 95 patients (90.5%) had initial successful results
      at 3 months (61.0% cured, 29.5% significantly improved) while 4 patients (3.8%)
      had slight improvement and 6 (5.7%) failed surgical correction. One year after
      the procedure, the success rate dropped to 81.9% (86 patients) with 46.7% cured
      and 35.2% significantly improved. Nine patients (8.6%) had slight improvement and
      10 patients (9.5%) failed surgical correction. Eight patients (7.6%) with initial
      unsatisfactory results underwent additional sessions of collagen injection and
      were subsequently either cured or had significant improvement. Twenty-three
      patients (21.9%) suffered a relapse. The mean time to relapse was 13.3 months,
      and 6 of those who relapsed underwent repeated injections with favorable results.
      Complications were minimal; 6 patients had temporary retention of urine, and 2
      patients had urinary tract infections. CONCLUSIONS: We conclude that
      glutaraldehyde cross-linked collagen injection is a simple and safe method of
      treatment for urinary stress incontinence. A longer follow-up period is necessary
      to assess the long-term efficacy of this treatment.

PMID- 9255663
TI  - Lower urinary tract dysfunction as persistent complication of radical
      hysterectomy.
AB  - BACKGROUND: This study was performed to evaluate late effects on the lower
      urinary tract after radical hysterectomy. METHODS: We studied 9 women treated
      with radical hysterectomy for cervical cancer. All patients underwent surgery
      more than 10 years age (range, 14 to 36 years). Six patients had urologic
      complications associated with lower urinary tract dysfunction. The remaining 3
      were referred for urinary tract abnormalities detected by radiologic
      examinations. Lower urinary tract function was evaluated with thorough history
      taking, laboratory examinations, intravenous urography, and conventional
      urodynamic studies. RESULTS: Obstructive voiding symptoms and/or urinary
      incontinence were observed in 7 patients. Uroflowmetry, which was assessable in 7
      patients, revealed intermittent flow and a significant amount of residual urine
      in all patients. Cystometry revealed impaired bladder sensation, detrusor
      areflexia, straining on voiding, and probable impaired relaxation of the
      sphincter in all assessable patients. In addition, decreased bladder compliance
      was observed in 5 patients. CONCLUSION: All of the examined patients had severe
      and complicated urinary tract dysfunctions, even at more than 10 years after
      surgery. Careful follow-up may be mandatory for patients after radical
      hysterectomy, because compensating factors tend to mask their urologic symptoms.

PMID- 9255664
TI  - Transurethral balloon laser thermotherapy for urinary retention in patients with
      benign prostatic hyperplasia who are at high surgical risk.
AB  - BACKGROUND: Twelve patients with benign prostatic hyperplasia and urinary
      retention, who were considered to be poor candidates for prostatectomy, were
      treated by transurethral balloon laser thermotherapy (TUBAL-T). The mean patient
      age was 78.9 years (range, 66 to 93 years) and the mean duration of bladder
      catheterization was 11 weeks (range, 2 to 48 weeks). METHODS: Irradiation into
      the prostatic tissue was done through 360 degrees with a neodymium: yttrium
      aluminum garnet (Nd:YAG) laser balloon placed in the prostatic urethra, with pain
      relief provided by using local topical anesthesia. The total laser dose was from
      45,000 to 123,376 J, with an average of 73,089 J. The irradiation time was from
      40 to 54 minutes, with an average of 45.2 minutes. RESULTS: Spontaneous voiding
      became possible in all patients at a mean of 2.8 days (range, 1 to 7 days) after
      irradiation. The mean catheter-free period was 20.5 months (range, 6 to 34
      months), with the longest being 34 months. The international prostatic symptom
      scores, quality-of-life scores, and peak uroflow rates showed substantial
      improvement after laser thermotherapy. To date, long-term resumption of
      spontaneous voiding was successfully achieved in 9 of 12 cases (75%). CONCLUSION:
      TUBAL-T is safe and effective alternative for treatment of urinary retention in
      patients with benign prostatic hyperplasia who are considered to be at high
      surgical risk.

PMID- 9255665
TI  - Prostate-specific antigen levels from a mass screening program using highly
      sensitive RIA kits.
AB  - BACKGROUND: This study was designed to evaluate the distribution of prostate
      specific antigen (PSA) levels of men in a mass screening program for prostatic
      disease. METHODS: A total of 763 men over 40 years of age underwent mass
      screening for prostatic disease in a Japanese prefecture using the highly
      sensitive Eiken kit and the Hybritech (Tandem-R) kit. The screening tests
      consisted of serum PSA determination, digital rectal examination, a questionnaire
      on symptoms, evaluation of prostate volume, and determination of the obesity
      rate. RESULTS: Serum PSA levels of all subjects were measured with both kits. The
      correlation between the values obtained by the Eiken kit and those of the Tandem
      R kit was high (r = 0.990), but the values of the former were slightly higher
      than those of the latter. Serum PSA weakly correlated with age, however, when
      estimated within decade age brackets, the levels of PSA showed significant
      differences among only 1 pair of groups stratified by age. In contrast, the
      levels of PSA showed significant differences among 9 pairs of groups stratified
      by prostate volume. CONCLUSION: A highly sensitive assay kit is useful to
      evaluate both the distribution of PSA levels and the relationship of PSA values
      to age and prostate volume of men in mass screening programs for prostatic
      disease, since approximately 40% of the subjects who underwent the present mass
      screening showed PSA values under 1.0 ng/mL, which have been the the lower limit
      of detection of many PSA kits.

PMID- 9255666
TI  - Electron microscopic study of the penile plaques and adjacent corpora cavernosa
      in Peyronie's disease.
AB  - BACKGROUND: We conducted ultrastructural studies to clarify the fine structure of
      penile plaques and adjacent corpora cavernosa, and the causative basis for the
      process, in Peyronie's disease. METHODS: Penile plaques and adjacent corpora
      cavernosa were obtained during surgical extirpation from 5 patients with
      Peyronie's disease. Control tissues from the tunica albuginea and adjacent
      corpora cavernosa were obtained at penile amputation from 2 patients with penile
      cancer. Prepared tissues were examined by using electron microscopy. RESULTS:
      Penile plaques were composed of collagen fibrils, amorphous particulate material,
      and fibroblasts in all patients. In 1 of 5 patients, myofibroblasts were found in
      the border area between the lesion and underlying structures. Smooth-muscle cells
      and endothelial cells resembling myofibroblasts were noted in adjacent corpora
      cavernosa. In this patient, the plaque progressively enlarged, and was removed
      within 1 year of onset of the induration. CONCLUSIONS: Fibromatosis in Peyronie's
      disease involves both fibroblasts and myofibroblasts, which undergo sclerosis in
      some phase. In addition, smooth-muscle cells and endothelial cells in the
      adjacent corpora cavernosa may be incorporated in the fibromatosis.

PMID- 9255667
TI  - Pharmacokinetic studies of mycophenolate mofetil in rat kidney allograft
      recipients.
AB  - BACKGROUND: A pharmacokinetic estimation of the immunosuppressive activity of
      mycophenolate mofetil (MPM) was performed in rats with transplanted kidney
      allografts. METHODS: Kidney allografts from Brown Norway rats were transplanted
      into Lewis rats using a microsurgical technique. MPM, at doses of 5, 10, 15 and
      25 mg/kg/day, was administered orally every day after transplantation.
      Pharmacokinetic studies were performed on days 7 and 14, and thereafter every 2
      weeks. RESULTS: After the administration of MPM, the plasma concentration of
      mycophenolic acid (MPA) increased rapidly, peaking at 15 to 30 minutes, and then
      decreased biexponentially. The peak concentration of MPA and the area under the
      plasma MPA concentration versus time curves (AUC) significantly correlated with
      the dosage. MPM administration at 5 and 10 mg/kg/day significantly prolonged the
      graft survival time from 7.1 days to 18.5 days and 85.0 days, respectively. The
      AUC values on day 7 after transplantation were 32.7 micrograms.h/mL and 38.6
      micrograms.h/mL in rats receiving 5 and 10 mg/kg/day, respectively. However, in
      rats receiving 15 mg/kg/day of MPM or more, the AUC value at 7 days was 78.8
      micrograms.h/mL, and almost all of these rats died from gastrointestinal
      toxicity. CONCLUSION: MPM monotherapy significantly prolonged rat kidney
      allograft survival, however, high dosages of MPM caused gastrointestinal
      toxicity. AUC measurements of the MPA concentration are suitable for the
      pharmacokinetic monitoring of MPM.

PMID- 9255668
TI  - Spontaneous loss of antibiotic-resistant plasmids transferred to Escherichia coli
      in experimental chronic bladder infection.
AB  - BACKGROUND: We investigated whether Escherichia coli that has been transformed
      with antibiotic-resistant plasmids spontaneously loses the plasmids while
      infecting the rat bladder. METHODS: A nontransmissible antibiotic-resistant
      plasmid was transferred to a clinically isolated strain of E. coli. A knotted
      thread holding the strain was implanted into the bladder of male Wistar rats. One
      or 4 weeks later, the total number of bacteria and that of plasmid-carrying
      bacteria were measured in the bladder. RESULTS: When plasmid-carrying E. coli
      alone was inoculated, most of the plasmid-carrying E. coli were replaced with
      plasmid-free E. coli. When plasmid-carrying and plasmid-free E. coli were
      simultaneously inoculated, this replacement was accelerated. CONCLUSION: These
      results suggest that E. coli carrying antibiotic-resistant plasmids spontaneously
      lose the plasmids as time passes, and thus become sensitive to antibiotics.

PMID- 9255669
TI  - Escherichia coli virulence factors and serotypes in acute bacterial prostatitis.
AB  - BACKGROUND: Escherichia coli is the most frequent pathogen in both acute
      bacterial prostatitis and acute uncomplicated urinary infections. To assess the
      virulence profiles of E. coli in acute prostatitis, the serotypes and virulence
      factor (VF) genotypes were determined. METHODS: We studied 107 E. coli isolates
      from cases of acute bacterial prostatitis, 76 isolates from acute pyelonephritis,
      194 isolates from acute Cystitis and 80 fecal isolates from healthy people. All
      pyelonephritis and cystitis isolates were from women. Seven urovirulence
      determinants were analyzed by DNA colony hybridization, including the genes for
      type 1 fimbria (pil), P fimbria (pap), S fimbria (sfa), afimbrial adhesin AFA-I
      (afaI), alpha-hemolysin (hly), cytotoxic necrotizing factor 1 (cnf1) and
      aerobactin (aer). O:H:K serotypes were also determined. RESULTS: With the
      exception of pil and afaI, all VFs were significantly more often associated with
      prostatitis, pyelonephritis and cystitis isolates than with the fecal isolates.
      The prevalence of sfa, hly and cnf1 was higher in prostatitis isolates than in
      pyelonephritis and cystitis isolates, and the pap+sfa+hly+cnf1+ genotype was
      dominant among prostatitis isolates (48.8%). Nine O serotype (O1, O2, O4, O6,
      O16, O18, O22, O25 and O75) accounted for 79.4%, 73.7% and 78.4% of the
      prostatitis, pyelonephritis and cystitis strains, respectively. There was an
      apparent correlation between serotype and genotype in uropathogenic E. coli.
      CONCLUSION: The predominance of O serotypes in female urinary tract infections
      and a high percentage of multiple VFs among the prostatitis isolates suggested
      that VFs play important roles in the pathogenesis of acute bacterial prostatitis.

PMID- 9255670
TI  - Effects of ethanol on responses of isolated rabbit urinary bladder and urethra.
AB  - BACKGROUND: Acute ethanol ingestion increases the risk of urinary retention in
      patients with benign prostatic hyperplasia (BPH). To elucidate the mechanism of
      this effect, we investigated the in vitro effects of ethanol on lower urinary
      tract function in rabbits. METHODS: The responses to various stimuli of muscle
      strips isolated from male rabbit bladder and urethra were determined in the
      presence of 0%, 0.5%, 1.0%, and 3.0% ethanol. RESULTS: Basal tension of tissue
      strips taken from the bladder and the urethra was reduced by ethanol in a dose
      dependent manner, as were bladder contractions induced by field stimulation,
      bethanechol, and ATP. Ethanol also reduced phenylephrine-induced contractions of
      the prostatic urethra. A high (3%) concentration of ethanol significantly reduced
      KCl-induced contraction of both the bladder and urethra, as well as urethral
      relaxation induced by field stimulation following contraction with 200 mumol/L
      phenylephrine. CONCLUSION: Responsiveness of the rabbit lower urinary tract was
      significantly reduced by exposure to ethanol. A similar decrease in tonus and
      contractility of the detrusor and inhibition of relaxation in the prostatic
      urethra may lead to urinary retention in men following acute ingestion of
      ethanol.

PMID- 9255671
TI  - Laparoscopic adrenalectomy for bilateral pheochromocytoma: a case report.
AB  - We report a case of bilateral (2.4-cm left and 6.5-cm right) adrenal
      pheochromocytoma in a 27-year-old man that was treated by laparoscopic
      adrenalectomy. The patient had no evidence of multiple endocrine neoplasia, type
      II. The left adrenalectomy was performed first, with the patient in a semilateral
      position, and then the patient was turned before the procedure was begun on the
      right side. His postoperative convalescence was uneventful, and he continues
      corticosteroid replacement therapy. Transperitoneal laparoscopic adrenalectomy
      can be a safe procedure for bilateral pheochromocytoma, if the patients are
      carefully selected and the procedures are performed by experienced
      laparoscopists.

PMID- 9255672
TI  - Family study of 2,8-dihydroxyadenine stone formation: report of two cases of a
      compound heterozygote for adenine phosphoribosyltransferase deficiency
      (APRT*J/APRT*Q0).
AB  - The family members of 2 formers of 2,8-dihydroxyadenine stones were examined for
      history, adenine phosphoribosyltransferase (APRT) activity, genotype, urinary
      sediment, and urinary constituents. The patients' father showed a genotype of
      APRT*1/APRT*Q0, and their mother showed APRT*1/APRT*J. Patients 1 and 2 were
      compound heterozygotes for adenine phosphoribosyltransferase deficiency
      (APRT*J/APRT*Q0), and APRT activities were 4.5% and 4.0% of normal, respectively.
      2,8-Dihydroxyadenine crystals could be seen in the urinary sediment. Treatment
      with allopurinol completely stopped new stone formation for 5 years in patient 1.

PMID- 9255673
TI  - Transitional cell carcinoma of the renal pelvis with vena caval tumor thrombus.
AB  - We report a case of transitional cell carcinoma of the renal pelvis with vena
      caval tumor thrombus. To our knowledge only 14 cases of transitional cell
      carcinoma of the renal pelvis protruding into the vena cava have been reported.
      The literature regarding these cases is reviewed, and the differential diagnosis
      of this tumor from renal cell carcinoma is discussed.

PMID- 9255674
TI  - Perirenal pseudolymphoma: a case report.
AB  - A right nephrectomy was performed on a 51 year-old female with a tumor
      surrounding the right kidney since the possibility of malignant lymphoma could
      not be excluded based on radiography or a needle biopsy. An immunohistological
      examination of the surgically-resected specimen confirmed a diagnosis of
      pseudolymphoma. A pseudolymphoma involving the urinary tract is rare, and this is
      only the second reported case of pseudolymphoma in the perirenal space.

PMID- 9255675
TI  - Diagnostic magnetic resonance-urography in an infant girl with an ectopic ureter
      associated with a poorly functioning segment of a duplicated collecting system.
AB  - We report on a case of an ectopic ureter associated with a duplicated collecting
      system in a 6-month-old girl. Results of conventional imaging and endoscopic
      studies, including intravenous pyelography, ultrasonography of the kidneys,
      cystoscopy, vaginoscopy, and vaginogram, were unremarkable. An ectopic ureter,
      extending from a poorly functioning upper pole of the ipsilateral duplicated
      kidney to its vaginal opening, was visible on the magnetic resonance-urogram. The
      imaging time was not extensive, and the need for patient sedation was minimal.
      Respiratory motion and intestinal gas did not interfere with the quality of the
      images. Magnetic resonance-urography may possibly be used as a primary diagnostic
      method for this anomaly when it is not detected by standard imaging techniques,
      or as a noninvasive substitute for some interventional studies in infants.

PMID- 9255676
TI  - Menkes' kinky hair disease associated with a large bladder diverticulum: a case
      report.
AB  - We report a 2 year-old boy with Menkes' kinky hair disease associated with a
      solitary huge bladder diverticulum. To our knowledge this is the first reported
      case treated successfully by surgical excision under general anesthesia, which
      has been previously considered hazardous due to the poor general condition of the
      patient.

PMID- 9255677
TI  - Small cell carcinoma of the prostate: a case report.
AB  - A case of small cell carcinoma of the prostate without a primary lesion in the
      lung was reported. The cancer was diagnosed after the patient complained of
      lumbago caused by bone metastasis. The tumor was 5.9 x 5.0 x 4.6 cm. The patient
      was treated with 4 courses of chemotherapy using cisplatin and etoposide. The
      tumor diminished to 4.0 x 4.0 x 3.5 cm after completion of the 4 courses of
      treatment. Prostatic antigen levels were less than 1.0 ng/mL during the therapy.
      Neuron-specific enolase levels were 35.9 ng/mL at the beginning of therapy, and
      decreased to 7.4 ng/mL after completion of 4 courses of treatment. The patient
      died 3 months after the completion of treatment. This regimen had some value for
      inhibiting the growth of small cell carcinoma.

PMID- 9255678
TI  - Six cases of prenatal and neonatal torsion of the spermatic cord.
AB  - Torsions of the spermatic cord occurring from the intrauterine period to the end
      of the first year of life are termed perinatal. These are divided into prenatal
      and postnatal torsions, depending on their occurrence in the intrauterine or
      postuterine period. From January 1984 to January 1996, 6 cases were identified at
      our institution, involving 4 prenatal and 2 postnatal extravaginal torsions of
      the spermatic cord. These cases are reviewed with regard to optimal therapeutic
      approaches for the treatment of both the affected gonad as well as the
      contralateral one, and whether the event occurred prenatally or postnatally. The
      authors also propose several clinical indications useful for obstetricians,
      pediatricians, urologists and nurses.

PMID- 9255679
TI  - Accessory scrotum with penoscrotal transposition and retrocerebellar arachnoid
      cyst: a case report.
AB  - A 2-year-old boy presented with an accessory scrotum associated with penoscrotal
      transposition and a perineal lipoma. He also had a retrocerebellar arachnoid
      cyst. The accessory scrotum was resected with concurrent scrotoplasty. The
      retrocerebellar arachnoid cyst was seen on a subsequent brain computed tomography
      scan and was left untreated because there was no evidence that the volume was
      increasing.

PMID- 9255680
TI  - Conduction properties of the inferior vena cava-tricuspid annular isthmus in
      patients with typical atrial flutter.
AB  - INTRODUCTION: A functional region of slow conduction located in the inferior
      right atrium has been postulated to be critical to the induction and maintenance
      of typical human atrial flutter. We reexamined the potential role of functional
      conduction delay in the annular isthmus between the tricuspid valve and the
      inferior vena cava; it is within this region that such delays have been
      postulated to occur, and where interruption of conduction by radiofrequency
      energy application has been shown to eliminate typical flutter. METHODS AND
      RESULTS: Thirty patients with type I atrial flutter (30 counterclockwise, 14
      clockwise) were studied. Counterclockwise and clockwise isthmus activation times
      adjacent and parallel to the tricuspid valve were measured during three
      conditions: (1) atrial pacing in sinus rhythm, (2) atrial flutter, and (3)
      entrainment of atrial flutter. During pacing in sinus rhythm at progressively
      shorter cycle lengths, both counterclockwise and clockwise isthmus activation
      times remained unchanged; decremental conduction prior to flutter induction or
      loss of capture was not observed. Counterclockwise isthmus activation time did
      not significantly differ during flutter (68 +/- 23 msec), inferolateral tricuspid
      annulus pacing (71 +/- 23 msec), or entrainment of flutter (72 +/- 23 msec).
      Similarly, clockwise isthmus activation times did not significantly differ
      between flutter (65 +/- 22 msec), proximal coronary sinus pacing (73 +/- 21
      msec), or entrainment of flutter (64 +/- 15 msec). CONCLUSION: Decremental
      conduction is not characteristic of activation through the isthmus when
      activation is assessed parallel and adjacent to the tricuspid annulus. Functional
      slowing or conduction delay does not develop in this region during typical atrial
      flutter.

PMID- 9255681
TI  - Structural determinants of slow conduction in the canine sinus node.
AB  - INTRODUCTION: To elucidate the role of tissue structure as a determinant of the
      unique conduction properties of the sinus node, we compared the spatial
      distribution of intercellular connections at gap junctions in the sinus node to
      the more rapidly conducting crista terminalis and left ventricle, which have been
      studied previously. METHODS AND RESULTS: Samples of four canine sinus nodes were
      prepared for electron microscopy. The total number and spatial orientation of
      neighboring myocytes connected by ultrastructurally identified intercalated disks
      and gap junctions to nine randomly selected index cells were determined by
      sequentially examining subserial sections. Sinus node cells were sparsely
      interconnected compared to the extent of interconnections observed previously in
      other tissues. A typical sinus node cell was connected to only 4.8 +/- 0.7
      neighbors compared with 11.3 +/- 2.2 cells in the left ventricle and 6.4 +/- 1.7
      cells in the crista terminalis. Sinus node interconnections occurred at small
      intercalated disks that usually connected cells in partial side-to-side and end
      to-end juxtaposition. In contrast, left ventricular myocytes are interconnected
      at large intercalated disks that adjoin many cells in pure side-to-side and end
      to-end orientations. Crista terminalis myocytes are connected primarily in end-to
      end fashion. The aggregate gap junction profile length per unit myocyte area was
      26.5 times greater in the left ventricle and 5.0 times greater in the crista
      terminalis than in the sinus node. CONCLUSION: Sinus node myocytes exhibit small,
      sparsely distributed gap junctions that interconnect cells in complex patterns of
      lateral and terminal apposition. These structural features are consistent with
      the unique conduction properties of the sinus node.

PMID- 9255682
TI  - Membrane refractoriness and excitation induced in cardiac fibers by monophasic
      and biphasic shocks.
AB  - INTRODUCTION: This modeling study examines the effect of low-intensity monophasic
      and biphasic waveforms on the response of a refractory cardiac fiber to the
      defibrillation shock. METHODS AND RESULTS: Two cardiac fiber representations are
      considered in this study: a continuous fiber and a discrete fiber that
      incorporates gap junctions. Each fiber is undergoing a propagating action
      potential. Shocks of various strengths and coupling intervals are delivered
      extracellularly at fiber ends during the relative refractory period. In a
      continuous fiber, monophasic shock strengths of three times the diastolic
      threshold either elicit no response or, for coupling intervals above 380 msec,
      reinitiate propagation. In contrast, biphasic shocks of same strength are capable
      of terminating the existing wavefronts by either invoking a nonpropagating
      response (coupling intervals 370 to 382 msec) that prolongs the refractory period
      or inducing wavefront collision (coupling intervals above 400 msec). The fiber
      response is similar for other shock strengths and when cellular discontinuity is
      accounted for. Thus, for a refractory fiber, biphasic shocks have only a small
      "vulnerable" window of coupling intervals over which propagation is reinitiated.
      CONCLUSION: At short coupling intervals, a significant extension of
      refractoriness is generated at regions where the biphasic shock induced
      hyperpolarization followed by depolarization. At large coupling intervals, the
      enhanced efficacy of biphasic shocks is associated with their ability to induce
      wavefront collision, thus decreasing the probability of reinitiating
      fibrillation. Overall, the defibrillation shock affects the tissue through the
      induced large-scale hyperpolarization and depolarization, and not through the
      small-scale transmembrane potential oscillations at cell ends.

PMID- 9255683
TI  - Na/K pump current in guinea pig cardiac myocytes and the effect of Na leak.
AB  - INTRODUCTION: Steady-state Na/K pump current (Ip) in adult guinea pig ventricular
      myocytes was studied to determine the effect on the Na/K pump of transmembrane Na
      leak, membrane potential, and pipette Na concentration. METHODS AND RESULTS:
      Using conventional whole cell, patch clamp techniques, Ip was identified as
      either Ko-sensitive or ouabain-sensitive current when most other membrane
      currents were inhibited. Control experiments showed that there were no Ko
      sensitive currents other than Ip under the conditions of our experiments. Ip was
      found to be similar to that reported by others being voltage dependent between 
      130 and 0 mV and having a half maximal activation by Nai of 28 mM. Ouabain
      sensitivity was also measured, and it was found that there were two binding sites
      with the high affinity site comprising 5% to 10% of the total and having an
      apparent affinity 1000-fold higher than the low affinity site. Apparent affinity
      of both sites was shifted about 10-fold (higher affinity) by increasing Nai from
      10 to 85 mM. When internally perfused with 0 Na solution, Na leak through the
      membrane was found to be linearly related to Na/K pump activity. In contrast to
      prior suggestions, Ip was not correlated with series resistance when there was a
      large transmembrane Na gradient. CONCLUSION: These data suggest that, under
      conditions of high transmembrane Na gradient, Na leak through the membrane plays
      a significant role in determining Na/K pump activity.

PMID- 9255684
TI  - Nonsustained reentry following successive stimulation of cardiac tissue through a
      unipolar electrode.
AB  - INTRODUCTION: Using numerical simulations, we predict that nonsustained reentry
      occurs following a strong, premature stimulus through a unipolar electrode.
      METHODS AND RESULTS: Our simulations were based on the bidomain model of cardiac
      tissue, and the active membrane properties were represented by the Beeler-Reuter
      model. An outwardly propagating wavefront was excited by an initial stimulus
      (S1). A second stimulus (S2) was then applied through the same electrode.
      Nonsustained reentry or reentrant-like behavior followed the S2 stimulus for both
      cathodal and anodal stimulation, and were associated with "break" stimulation but
      not with "make" stimulation. The direction of spiral-wave rotation was reversed
      when the polarity of the stimulus was reversed. These complex dynamics occur only
      for a narrow window of S1-S2 intervals. During anodal S2 stimulation, two
      different modes of reentry exist. Our simulations also explain the "no response"
      phenomenon. CONCLUSION: Our mathematical model predicts that both anodal and
      cathodal unipolar S2 stimulation results in reentry. This behavior arises from an
      interaction of virtual anodes and cathodes surrounding the stimulating electrode.

PMID- 9255685
TI  - Prevention of action potentials during extracellular electrical stimulation of
      long duration.
AB  - INTRODUCTION: This study investigated if action potentials can be prevented by
      electrical field stimuli of long duration. METHODS AND RESULTS: The transmembrane
      potential was recorded by a double-barrel micro-electrode during field
      stimulation given across a papillary muscle from 10 guinea pigs. After 10 stimuli
      (S) with a 200-msec S-S interval, a 400-msec square wave shock was given just
      before or after the end of the effective refractory period following the 10th
      stimulus through electrodes 1 cm on either side of the papillary muscles. Another
      two stimuli (S' and S") having the same 200-msec S-S interval were given during
      the shock pulse to test if the action potentials induced by these two stimuli
      could be prevented by the shock. The shock strength was increased until the shock
      field prevented the action potentials induced by the S' and S" stimuli. The
      resting membrane potential was -85.5 +/- 2.9 mV. For shocks causing
      depolarization at the recording site, the field strength required to prevent S'-
      and S"-induced action potentials was 1.5 +/- 0.4 V/cm, which depolarized the
      transmembrane potential to -55.3 +/- 8.9 mV and -58.1 +/- 7.2 mV from the resting
      membrane potential at the time of the S' and S" stimuli, respectively. The
      strength of shocks causing hyperpolarization required to prevent S'- and S" 
      induced action potentials was 5.0 +/- 0.8 V/cm, which hyperpolarized the
      transmembrane potential to -105 +/- 6.5 mV and -115.6 +/- 6.9 mV from the resting
      membrane potential at the time of the S' and S" stimuli, respectively.
      CONCLUSION: Both depolarization and hyperpolarization caused by an electrical
      field can prevent action potentials.

PMID- 9255686
TI  - Effects of 2,3-butanedione monoxime on atrial-atrioventricular nodal conduction
      in isolated rabbit heart.
AB  - INTRODUCTION: 2,3-Butanedione monoxime (BDM) has been found to reversibly block
      cardiac contraction, without blocking electrical conduction. This study
      characterizes the dose-dependent effects of BDM on the conduction through the
      atrioventricular node (AVN) of rabbit heart. METHODS AND RESULTS: Thirteen
      isolated atrial-AVN preparations were used in control, during and after exposure
      to 5, 10, and 20 mM BDM. Anterograde and retrograde pacing protocols were used to
      obtain the Wenckebach cycle length, effective and functional refractory periods
      of the AVN, index of AVN conduction delay (the area under the AVN conduction
      curve), as well as index of intra-atrial conduction delay between the AVN inputs.
      Compared to control, 5 and 10 mM BDM produced either shortening or no effect on
      all of the above parameters except a slight (6% and 14%, respectively) increase
      in the intra-atrial delay. At 20 mM, BDM produced a further increase in the intra
      atrial delay (up to 50%) as well as in the retrograde AVN conduction delay (up to
      16%), while the characteristics of the anterograde conduction were still
      improved. The effects of perfusion with BDM on these parameters were reversible
      after washout. CONCLUSIONS: Aside from its known effect as an electromechanical
      uncoupler, BDM reversibly altered some of the electrical responses of the AVN.
      Most of these alterations, however, did not impede but rather improved AVN
      conduction. Since a dose of 10 mM is sufficient to fully eliminate undesirable
      motion, BDM should be considered a safe and valuable tool in AVN studies in vitro
      requiring a mechanically quiescent preparation.

PMID- 9255688
TI  - Implantable cardioverter defibrillator oversensing during periods of rate-related
      bundle branch block.
AB  - A patient with an implantable cardioverter defibrillator (ICD) and a dual chamber
      pacemaker experienced inappropriate ICD therapies only during periods of rate
      dependent right bundle branch block. Analysis of both stored and real-time ICD
      electrograms was critical to correctly diagnosing the problem and offering a
      solution.

PMID- 9255687
TI  - Radiofrequency catheter ablation of sustained monomorphic ventricular tachycardia
      in hypertrophic cardiomyopathy.
AB  - INTRODUCTION: Incessant monomorphic ventricular tachycardia (VT) with a right
      bundle branch block morphology and a northwest axis is a rare arrhythmic
      complication in a patient with hypertrophic cardiomyopathy and apical left
      ventricular aneurysm. METHODS AND RESULTS: The origin of this VT was localized
      using the following criteria: the presence of entrainment without fusion, equal
      intervals from the stimulus to the beginning of the QRS complex and from the
      electrogram to the QRS complex during VT, and the first postpacing interval
      identical to the tachycardia cycle length. Radiofrequency energy applied to the
      septoapical part of the apical left ventricular aneurysm terminated the
      tachycardia within 2 seconds. CONCLUSION: Using criteria to guide radiofrequency
      (RF) ablation of VT in patients with coronary artery disease, an incessant
      monomorphic VT in a patient with hypertrophic cardiomyopathy was successfully
      ablated.

PMID- 9255689
TI  - High-rate atrial pacing as an innovative bridging therapy in a neonate with
      congenital long QT syndrome.
AB  - INTRODUCTION: The neonatal presentation of the long QT syndrome is rare, although
      it is frequently accompanied by life-threatening arrhythmias. Infants may not
      survive childhood despite traditional management with beta-adrenergic blockade
      and pacing. METHODS AND RESULTS: This case describes a newborn with a long QT
      interval, T wave alternans, intermittent 2:1 AV block, ventricular arrhythmias,
      and a family history of sudden death. After failing medical therapy, conventional
      VVI and DDD pacing were unsuccessful due to prolonged ventricular refractoriness
      and proarrhythmia. At 2 months of life, the child was treated with high-rate (180
      ppm) atrial pacing to produce intentional 2:1 AV block. Following an episode of
      possible syncope at 16 months of age, an automatic implantable cardioverter
      defibrillator (ICD) was added. Finally, as recently reported, acutely induced
      hyperkalemia led to both a marked decrease in QTc and functional improvement in
      repolarization (consistent 1:1 AV conduction at rates to 180 beats/min).
      Spironolactone and dietary potassium were added and have produced the same
      effects chronically. CONCLUSIONS: High-rate atrial pacing with 2:1 AV block is
      presented as a novel and "bridging" therapy for neonatal long QT syndrome and 2:1
      AV block with ventricular arrhythmias. Definitive therapy with ICD implantation
      was then possible when patient size was substantially increased. The
      electrophysiologic response to intentional elevation of the serum potassium
      suggests a genetic defect in an inward potassium channel and demonstrates a
      possible therapy of long QT syndrome in some future patients.

PMID- 9255690
TI  - Pharmacologic management of atrial fibrillation.
AB  - In an era when many electrophysiologic problems are routinely treated with
      invasive procedures or implantable devices, drugs remain the cornerstones of
      treatment for atrial fibrillation. Atrial fibrillation may present as an episodic
      rhythm in patients who are primarily in sinus rhythm or it may be manifested as
      rhythm disorder that is permanent. Patients who appear to have an episodic rhythm
      disorder may be found to be in atrial fibrillation permanently when followed for
      long periods of time, and prognosis in the two forms is similar. It is,
      therefore, useful to consider them different manifestations in the same spectrum
      of disease. This review will address pharmacologic approaches designed to: (1)
      slow ventricular response; (2) restore sinus rhythm; (3) reduce occurrences of
      atrial fibrillation; and (4) prevent thromboembolic complications.
      Nonpharmacologic approaches to treating atrial fibrillation will be briefly
      reviewed.

PMID- 9255691
TI  - ICD-antiarrhythmic drug and ICD-pacemaker interactions.
AB  - Antiarrhythmic drugs and separate bradycardia pacing systems are prescribed
      commonly in patients with implantable cardioverter defibrillators (ICDs). Adverse
      effects of antiarrhythmic drugs on ICD function and adverse interactions between
      ICDs and pacemakers have been documented. The effect of antiarrhythmic drugs on
      the defibrillation threshold (DFT) in patients has not been well assessed. Most
      studies have been performed in animal models in which cardiac function was normal
      and drug doses were supraphysiologic. In addition, most studies have utilized
      monophasic defibrillation shock waveforms and epicardial lead systems. Despite
      the lack of clinical data applicable to current defibrillation systems, it
      appears that chronic amiodarone administration causes a significant DFT increase.
      In addition, antiarrhythmic drugs can influence antitachycardia pacing and
      tachycardia sensing. Defibrillation shocks can cause transient failure of
      pacemaker sensing and pacing, and cause spurious pacemaker reprogramming.
      Pacemaker function can result in ICD oversensing, leading to inappropriate
      therapy, or cause ICD undersensing, potentially resulting in failure to deliver
      therapy during ventricular fibrillation. The susceptibility of an ICD to
      undersensing appears related to the amplitude of the pacing stimulus artifact
      recorded by the ICD rate-sensing circuit and to the characteristics of the
      fibrillation electrogram. Preliminary data suggest that undersensing of
      ventricular fibrillation by current ICDs is an unlikely event.

PMID- 9255692
TI  - Incessant long RP tachycardia: what is the tachycardia mechanism?

PMID- 9255693
TI  - Annotation: computers for learning: psychological perspectives.
AB  - The research literature on the use of computers in support of learning is already
      vast. In this review, the focus is on children's learning, and on the way in
      which psychological theories of learning have informed (and to a lesser extent,
      been informed by) developments in the field of computer-based learning.
      Associationist, constructivist, and social-constructivist approaches are
      explored, and issues of equity, access, and special learning needs are addressed.
      It is concluded that computers have led to, and will continue to lead to,
      significant changes in both what and how children learn.

PMID- 9255694
TI  - A competency-based model of child depression: a longitudinal study of peer,
      parent, teacher, and self-evaluations.
AB  - In a two-wave longitudinal study of third and sixth graders (N = 617), we
      obtained self-reports of depression and peer, teacher, parent, and self-reports
      of competence in five domains: academic, social, attractiveness, conduct, and
      athletic. Competency evaluations by others predicted change in self-perceived
      competence over time for girls, but not for boys. Depression predicted change in
      self-perceived competence over time for boys but not for girls. Among girls, the
      relative importance of parent, teacher, and peer appraisals shifted from third to
      sixth grade. For both boys and girls, self-perceptions of competence predicted
      change in depression scores over time. Furthermore, self-perceived competencies
      mediated the relation between competency appraisals by others and children's self
      reported depression. Results are interpreted in light of a competency-based model
      of child depression.

PMID- 9255695
TI  - Dimensions and disorders of adolescent adjustment: a quantitative genetic
      analysis of unselected samples and selected extremes.
AB  - One of the fundamental questions for developmental psychopathology concerns the
      etiological links between the normal and abnormal. To what extent do disorders
      differ quantitatively or qualitatively from variation in the normal range?
      Genetic research on the normal and the abnormal differs in terms of concepts,
      methods, statistics, and target audiences. An approach, referred to as "DF"
      analysis, provides a framework for integrating these two worlds of genetic
      analysis. We applied traditional correlational analyses as well as DF (DeFries &
      Fulker, 1985) analyses to mother and father ratings of adjustment of adolescent
      siblings in a 3-year longitudinal twin and step-family study. At wave 1, the
      sample included 720 sibling pairs (average age of 12.9 years for the younger
      sibling and 14.5 years for the older siblings) and, in wave 2, 395 pairs still
      living at home. Both correlational analyses of the entire sample and DF analyses
      of selected extremes suggested moderate genetic influence and modest shared
      environmental influence for internalizing and externalizing behavior problems.
      Similar estimates were found for unselected individual differences and selected
      extreme groups. A framework is proposed that focuses on quantifying the
      etiologies of disorders (QED) as measured on continuous dimensions.

PMID- 9255696
TI  - Are people with autism and Asperger syndrome faster than normal on the Embedded
      Figures Test?
AB  - Previous work suggests children with autism show superior performance (in
      relation to their general mental age) on the Embedded Figures Test (EFT). Frith
      interprets this as showing that they have "weak central coherence". In Experiment
      1, using an adult level version of this task, we aimed to replicate and extend
      this finding, first, by collecting response time (RT) data; second, by testing
      adults with autism of normal intelligence; and third, by testing a group of
      adults with Asperger syndrome, in order to test for differences between autism
      and Asperger syndrome. Both clinical groups were significantly faster on the EFT.
      In Experiment 2, we investigated if this difference was due to a preference for
      local over global processing, using a novel drawing task based on the classical
      Rey Figure. The clinical groups did not differ significantly on this test, but
      there was a trend towards such a difference. Alternative explanations for the EFT
      superiority in autism and Asperger syndrome are considered.

PMID- 9255697
TI  - Information processing in clinically depressed and anxious children and
      adolescents.
AB  - The investigation of cognitive content and processes in childhood anxiety and
      depression has lagged behind similar research in the adult population. What
      studies do exist have largely restricted themselves to examining the nature of
      the thoughts that anxious and depressed children report. There is almost no
      research examining the ways in which anxious and depressed children perceive,
      attend to, remember, or think and make judgements about, emotional material. The
      present study investigated the subjective probability judgements that anxious and
      depressed children make concerning future negative events. Subjects generated
      probability estimates either for themselves or for other children for a range of
      events on a visual analogue scale. Events were either physically-threat-related
      or socially-threat-related. The results revealed no differences of interest with
      respect to type of threat but interesting differences between the groups with
      respect to reference. Depressed subjects estimated that events were equally
      likely to happen to themselves as to other children whereas both the controls and
      anxious children estimated that negative events were more likely to happen to
      others than to themselves, with this effect being stronger in the anxious group.
      These results are discussed in the context of the adult literature and also the
      limited literature on emotion-related cognitive processing in children.

PMID- 9255698
TI  - Sibling sex ratio of boys with gender identity disorder.
AB  - Sibling sex ratio (the ratio of brothers to sisters) was calculated for 444 boys
      with gender identity disorder (or with behaviors consistent with this diagnosis).
      The probands were ascertained from several researchers with expertise with this
      disorder and from the English language case report literature between 1938 and
      1995. Among the probands with at least one sibling (N = 333), the results showed
      that boys with gender identity disorder had a significant excess of brothers to
      sisters, 131.1:100, when compared with the expected secondary sex ratio of
      106:100. The excess of brothers replicated a previous study by Blanchard, Zucker,
      Bradley, and Hume (1995), in which the sibling sex ratio was 140.6:100. Further
      analyses showed that the probands were born later relative to their brothers than
      they were relative to their sisters. These findings are amenable to several
      psychosocial and biological explanations, which require further investigation.

PMID- 9255699
TI  - Childhood, adolescent, and young adult predictors of suicidal behaviors: a
      prospective study of African Americans.
AB  - This study examined the lifetime prevalence of suicidal behaviors and their
      relation to social integration, depression, and aggression/substance use in a
      cohort of African Americans followed prospectively from first grade to age 32.
      Lifetime depressive moods in adulthood, lifetime use of cocaine, and frequent
      mobility were associated with suicidal behaviors for both males and females. For
      males, having been in a mother-alone or mother-absent family at age 6, childhood
      psychopathology, and not being married were related to suicidal behaviors.
      Females who reported high assault behavior in adolescence were more likely to
      report suicide attempts. The results suggest that social integration, depression,
      and aggression/drug use are important risk factors for suicidal behaviors in this
      African American population.

PMID- 9255700
TI  - Detection of major and minor depression in children and adolescents: evaluation
      of the Mood and Feelings Questionnaire.
AB  - The detection of major and minor depression in children and adolescents was
      evaluated in an outpatient sample of 113 children employing the Mood and Feelings
      Questionnaire (both child and parent versions) and the K-SADS interview.
      Differences between depressed and nondepressed groups, those with major or minor
      depression, and depressed children compared with those comorbid for anxiety, were
      examined. Our findings support the validity of the MFQ as a screening instrument
      for major and minor depression in a population with a high proportion of
      depressed cases. High agreement between parent and child ratings was found, with
      cognitive items being the best predictors of depression.

PMID- 9255701
TI  - Malaise scores in adulthood of children and young people who have been in care.
AB  - Data from the National Child Development Study are used to assess the risk of
      high Malaise scores (indicating a tendency towards depression) amongst young
      adults at age 23 and 33. Results indicate that adults who have been in care are
      more likely to have high Malaise scores than are those who have not been in care.
      For men this risk increases as they grow older. Those with an early experience of
      social disadvantage are also more vulnerable to a high Malaise score than those
      not so disadvantaged. Overall, when other factors are controlled, the risk of a
      high Malaise score in adulthood is significantly greater for young adults who
      have been in care than those who have experienced severe social disadvantage in
      their childhood, except for women at age 33, where an early experience of social
      disadvantage carries a greater risk than the care experience.

PMID- 9255702
TI  - The Strengths and Difficulties Questionnaire: a research note.
AB  - A novel behavioural screening questionnaire, the Strengths and Difficulties
      Questionnaire (SDQ), was administered along with Rutter questionnaires to parents
      and teachers of 403 children drawn from dental and psychiatric clinics. Scores
      derived from the SDQ and Rutter questionnaires were highly correlated; parent
      teacher correlations for the two sets of measures were comparable or favoured the
      SDQ. The two sets of measures did not differ in their ability to discriminate
      between psychiatric and dental clinic attenders. These preliminary findings
      suggest that the SDQ functions as well as the Rutter questionnaires while
      offering the following additional advantages: a focus on strengths as well as
      difficulties; better coverage of inattention, peer relationships, and prosocial
      behaviour; a shorter format; and a single form suitable for both parents and
      teachers, perhaps thereby increasing parent-teacher correlations.

PMID- 9255703
TI  - Human jejunal effective permeability and its correlation with preclinical drug
      absorption models.
AB  - This review focuses on intestinal permeability measurements in humans and various
      aspects of in-vivo transport mechanisms. In addition, comparisons of human data
      with preclinical models and the blood-brain barrier is discussed. The regional
      human jejunal perfusion technique has been validated by several crucial points.
      One of the most important findings is that there is a good correlation between
      the measured human effective permeability values and the extent of absorption of
      drugs in humans determined by pharmacokinetic studies. We have also shown that it
      is possible to determine the effective permeability (Peff) for carrier-mediated
      transported compounds, and to classify them according to the proposed
      Biopharmaceutical Classification System (BCS). Furthermore, it is possible to
      predict human in-vivo permeability using preclinical permeability models, such as
      in-situ perfusion of rat jejunum, the Caco-2 model and excized intestinal
      segments in the Ussing chamber. The permeability of passively transported
      compounds can be predicted with a particularly high degree of accuracy. However,
      special care must be taken for drugs with a carrier-mediated transport mechanism,
      and a scaling factor has to be used. It is also suggested that it is possible to
      roughly estimate the permeability of the blood-brain barrier using measurements
      of intestinal permeability, even if the quantitative role of efflux of P
      glycoprotein(s) in-vivo still remains to be clarified. Finally, the data obtained
      in-vivo in humans emphasize the need for more clinical studies investigating the
      effect of physiological in-vivo factors and molecular mechanisms influencing the
      transport of drugs across the intestinal and as well as other membrane barriers.
      It is also important to study the effect of anti-transport mechanisms, such as
      efflux by P-glycoprotein(s), and gut wall metabolism, for example CYP 3A4, on the
      bioavailability.

PMID- 9255704
TI  - Characterization of the block structure and molecular weight of sodium alginates.
AB  - Sodium alginates are widely used within the pharmaceutical sciences, yet the
      molecular characteristics of these materials are frequently not stated. In this
      study, a range of characterization techniques is applied to five sodium alginate
      samples and the data compared, both between techniques and with the information
      obtained from the manufacturer. The mannuronic acid to guluronic acid (MG) ratio
      and the distribution of uronic acid residues of five sodium alginate samples have
      been measured using circular dichroism and NMR, with circular dichroism yielding
      MG ratios between 42.1 and 63.6%, depending on the grade of alginate used. The MG
      ratios obtained from NMR studies were in broad agreement with these values, and
      the technique also yielded information on the distribution of uronic acid
      residues within each batch; this was again found to vary considerably (NG > 1
      values ranging from 6.9 to 17.5). It was noted that samples with similar MG
      ratios could have markedly different chain-distribution characteristics. The
      uronic acid ratio ranges obtained from the manufacturers were found to be in good
      agreement with those found experimentally. Intrinsic viscosity measurements were
      used to compare the molecular weights of the samples; values between
      approximately 12,000 and 180,000 were obtained for the different batches. The
      study has enabled comparison of different methods for characterization of sodium
      alginate samples, highlighting their relative merits and the possible protocols
      that might be adopted. A critical discussion is given of the individual and
      combined use of these techniques and the relevance of such studies to the
      rational design and quality control of alginate-based pharmaceutical systems.

PMID- 9255705
TI  - The expanded Hansen approach to solubility parameters. Paracetamol and citric
      acid in individual solvents.
AB  - In this study two solubility-parameter models have been compared using as
      dependent variables the logarithm of the mole fraction solubility, lnX2e, and
      ln(alpha)/U (originally used in the extended Hansen method), where alpha is the
      activity coefficient and U is a function of the molar volume of the solute and
      the volume fraction of the solvent. The results show for the first time the
      proton-donor and -acceptor hydrogen-bonding capacities of paracetamol, as
      measured by the acidic and basic partial-solubility parameters. The influence of
      solvents on the differential scanning calorimetry (DSC) pattern of the solid
      phases was also studied in relation to the solubility models tested. Citric acid
      was chosen as a test substance because of its high acidity and its proton donor
      capacity to form hydrogen bonds with basic solvents. The partial acidic and basic
      solubility parameters obtained from multiple regression were consistent with this
      property, validating the model chosen. The results show that the more direct
      lnX2e variable was more suitable for fitting both models, and the four-parameter
      model seemed better for describing the interactions between solvent and solute.

PMID- 9255706
TI  - Potential efficacy of a delta 5-aminolevulinic acid bioadhesive gel formulation
      for the photodynamic treatment of lesions of the gastrointestinal tract in mice.
AB  - A delta 5-aminolevulinic acid (ALA) bioadhesive gel has been developed and
      evaluated in an in-vivo mouse model for photodynamic treatment of gastric cancer
      or Barrett's oesophagus. Four gels were tested: noveon AA-1, keltrol T, lutrol
      and blanose. An initial in-vitro study of gel adhesion showed that noveon and
      keltrol had longer polyethylene transit times than lutrol and blanose. In-vivo
      assays indicated that protoporphyrin IX was synthesized by gastric mucosa when
      ALA-noveon and ALA-lutrol were used (preferable results for noveon). Keltrol was
      eliminated from the study after these investigations. Only ALA-noveon gel was
      retained for studies of the relationship between ALA dose and fluorescence.
      Fluorescence measurements in-vivo showed that ALA concentration and application
      time had an influence on protoporphyrin IX synthesis. Maximum intensity (2091
      counts s-1) was found with 2 mg mL-1 ALA, and fluorescence intensities differed
      with application time, reaching 1805 counts s-1 after 240 min. ALA-noveon,
      showing good adhesion and enabling efficient diffusion of ALA at a pH < 6, was
      considered the best formulation for maintaining ALA stability.

PMID- 9255707
TI  - Effect of oral adsorbent AST-120 on cyclosporin absorption in rats.
AB  - The oral adsorbent AST-120 is used to inhibit the progression of renal failure by
      adsorbing uraemic toxins in the gastrointestinal tract. When AST-120 is
      administered to patients receiving immunosuppressive medicines, it is important
      to study the effect of AST-120 on the amount of these and other drugs absorbed.
      We have, therefore, studied the in-vitro adsorption of cyclosporin by AST-120 and
      investigated the effect of oral administration of AST-120 on the absorption of
      cyclosporin in rats. The in-vitro adsorption ratios of AST-120 for cyclosporin
      were more than 80%. When pure cyclosporin powder was administered with AST-120,
      blood cyclosporin concentrations were significantly higher than when cyclosporin
      was administered alone. When cyclosporin dissolved in medium-chain triglyceride
      was administered to rats by intramuscular injection there was no significant
      difference in the blood cyclosporin concentration of rats given combined AST-120
      and cyclosporin and those given cyclosporin alone. There was no significant
      difference between the serum concentration of total bile acids, in rats receiving
      combined oral AST-120 and cyclosporin dissolved in olive oil, and those receiving
      orally solely a solution of cyclosporin dissolved in olive oil. These results
      suggest that oral administration of AST-120 accelerates the absorption of orally
      administered cyclosporin from the gastrointestinal tract and does not affect the
      metabolism of cyclosporin. When a solution of cyclosporin in olive oil is
      administered orally, however, oral administration of AST-120 has no influence on
      cyclosporin absorption and does not affect the enterohepatic circulation of bile
      acids.

PMID- 9255709
TI  - Oral delivery and fate of poly(lactic acid) microsphere-encapsulated interferon
      in rats.
AB  - In the light of previous findings which suggest that particulate material can be
      absorbed and thence systemically disseminated from the gastrointestinal tract, we
      have investigated the oral uptake and distribution of soluble and microsphere
      encapsulated radiolabelled interferon-gamma. For trace-loaded (0.01% w/w
      interferon) microspheres, a quite different distribution of radioactivity was
      observed in-vivo 15 and 240 min after oral administration, in comparison with the
      control group which received equivalent doses of unencapsulated interferon-gamma.
      Thyroid gland activity in control animals killed at these times was significantly
      higher than that detected in those rodents receiving trace amounts of
      microencapsulated interferon-gamma (P < or = 0.05). For poly(L-lactide) particles
      with higher interferon loadings (0.97% w/w interferon-gamma) the distinction
      between the two experimental groups was less significant. During incubation in
      vitro, the trace-loaded particles released a significantly lower percentage of
      interferon-gamma in comparison with 0.97% w/w loaded microspheres (P < or = 1).
      Bio-distribution data from rats treated orally with trace amounts of
      unencapsulated and microencapsulated interferon-gamma leads us to the tentative
      conclusion that microencapsulation of proteins markedly affects oral uptake, and
      possibly post-absorption pharmacokinetic parameters also.

PMID- 9255708
TI  - Biodistribution of cyclosporin encapsulated in liposomes modified with
      bioadhesive polymer.
AB  - The purpose of this investigation was to study the possibility of renewing the
      immunosuppressive activity of cyclosporin by formulating the compound in
      liposomes modified with bioadhesive polymers. The liposomes prepared were
      evaluated both pharmacokinetically and pharmacodynamically. Tissue distribution
      and plasma pharmacokinetics of cyclosporin and model dye, sudan black, which is
      as hydrophobic as cyclosporin, were studied in rats after intravenous infusion
      (10 mg kg-1). The immunosuppressive efficacy of liposomal cyclosporin
      preparations was studied in the allogenic rat-heart-transplantation model, where
      cyclosporin therapy (10 mg kg-1) continued for one week. The entrapment of sudan
      black in liposomes modified with bioadhesive polymers resulted in higher sudan
      black delivery to the spleen and the liver than with standard sudan-black-loaded
      liposomes. Among the modified liposomes, those modified with carbopol 941 showed
      the most remarkable enhancing effect on the delivery of sudan black to these
      organs and total plasma clearance of sudan black decreased to 38.6 +/- 7.8 mL h-1
      kg-1 (standard liposomes, 58.9 +/- 6.4 mL h-1 kg-1). Delivery of cyclosporin to
      the spleen and the liver was increased approximately twofold by modifying the
      liposomes with carbopol 941. In the preliminary study on the allogenic rat-heart
      transplantation model, the mean survival days of the graft were 18.8 +/- 2.9 days
      for the group receiving cyclosporin liposomes modified with carbopol 941, 14.2 +/
      4.4 days for the group receiving standard cyclosporin liposomes and 7.6 +/- 0.5
      days for the group receiving cyclosporin solution. The encapsulation of
      cyclosporin in liposomes modified with bioadhesive polymer enhanced the residence
      time of cyclosporin in the systemic circulation, resulting in approximately
      twofold greater delivery of cyclosporin to the spleen and liver. However, in the
      allogenic rat-heart-transplantation model no significant difference was detected
      between the immunosuppressive efficacy of cyclosporin encapsulated in bioadhesive
      polymer-modified liposomes and that encapsulated in standard liposomes.

PMID- 9255711
TI  - A residence-time distribution analysis of the hydrodynamics within the intestine
      in man during a regional single-pass perfusion with Loc-I-Gut: in-vivo
      permeability estimation.
AB  - The goal of this study was to determine the most appropriate hydrodynamic model
      for the Loc-I-Gut in-vivo perfusion system. The general mixing-tank-in-series
      model, which can approximate single mixing tank and laminar and plug-flow
      hydrodynamics, was fitted to the observed experimental residence-time
      distribution curves for the non-absorbable marker [14C]PEG 4000. The residence
      time distribution analysis shows that the hydrodynamics of the perfusion solution
      within the jejunal segment in man is well approximately by a model containing on
      average between 1-2 mixing tanks in series. The solution is well mixed when using
      perfusion rates of 2.0, 3.0 and 6.0 mL min-1. The average mean residence time
      estimates from the fitted residence-time distribution were 12 +/- 7.6, 15 +/- 4.2
      and 7.7 +/- 4.6 min, respectively, at these three perfusion rates. The mean
      volumes of the segment (Vs) were 25 +/- 15, 45 +/- 12 and 46 +/- 27 mL,
      respectively. There were no statistical differences between 2.0, 3.0 and 6.0 mL
      min-1 in respect of the number of mixing tanks (n) and mean residence times. This
      residence-time distribution analysis indicates that the luminal fluid in the Loc
      I-Gut perfusion system is well-mixed, and that permeability calculations based on
      the well-mixed assumption most closely approximate the actual local (average)
      membrane permeability within the perfused segment.

PMID- 9255710
TI  - Effect of the size of liposomes on the transfer and uptake of carboxyfluorescein
      by the perfused human term placenta.
AB  - The effect of the size of liposomes on the uptake and transfer of the low
      molecular-weight, hydrophilic and polar molecule carboxyfluorescein has been
      determined across the perfused human term placenta. Carboxyfluorescein
      encapsulated neutral liposomes of three different sizes were prepared from
      equimolar concentrations of lecithin and cholesterol. Size distribution,
      encapsulation efficiency and stability of liposomes in blood-based media were
      determined. The concentration of carboxyfluorescein was measured
      spectrophotometrically. The transplacental transfer and placental uptake of free
      carboxyfluorescein (control data) were respectively 1.9 +/- 0.2 and 5.0 +/- 0.7%
      of initial dose. The placental uptake and foetal concentration of
      carboxyfluorescein were significantly increased by small liposomes (P < 0.05),
      and reduced by large (0.82 +/- 0.13%; P < 0.05) and multilamellar liposomes (0.32
      +/- 0.11%). There was a negative correlation between liposome size and
      transplacental transfer (y = -0.53 + 0.9x; r = 0.96; P < 0.001; n = 24) and
      placental uptake of carboxyfluorescein (y = -5.9 + 6.5x; r = 0.84; P < 0.001; n =
      24). The study indicates that placental uptake and transfer rate of liposomal
      carboxyfluorescein were dependant upon the size of liposomes.

PMID- 9255713
TI  - Cholinergic modulation of electrogenic ion transport in different regions of the
      rat small intestine.
AB  - Acetylcholine acting via muscarinic receptors located in the intestinal mucosa
      controls ion and fluid transport. This study examined the pathway(s) by which
      cholinergic receptors mediate secretion in rat isolated duodenum, jejunum and
      ileum using the short-circuit current (Isc) as an index of electrogenic CL-
      secretion. Carbachol and bethanechol induced electrogenic CL- transport which was
      insensitive to the neural blocker tetrodotoxin, indicating their direct action on
      the enterocytes. Functional characterization of electrogenic secretion activated
      via muscarinic receptors on jejunal and ileal enterocytes was achieved by use of
      selective muscarinic antagonists in the presence of tetrodotoxin. In both regions
      the rank order of potency of these compounds (atropine > 4-diphenylacetoxy-N
      piperidine methiodide (4-DAMP) > hexahydro-sila-difenidol (HHSiD) > pirenzepine >
      methoctramine) indicated the M3 receptor subtype. Secretion activated by the
      muscarinic agonist 4-[[(3-chlorophenyl)amino]carbonyl]-N,N, N-trimethyl-2-butyn-1
      ammonium chloride (McN-A-343) was sensitive to tetrodotoxin and pirenzepine but
      not to the ganglionic blocker, hexamethonium, indicating the M1 receptor subtype
      on post ganglionic neurons. Regional differences for bethanechol-activated
      secretion showed an increasing gradient in secretory capacity (Isc max) in a
      proximal-to-distal direction along the small intestine. Responses to McN-A-343
      also showed regional differences but these were unlike those of bethanechol.
      These results show that cholinomimetic-induced electrogenic CL- secretion in rat
      isolated small intestine appears to be mediated by two dissimilar populations of
      muscarinic receptor: M3 muscarinic receptors positioned on enterocytes and M1
      muscarinic receptors sited on submucosal neurons.

PMID- 9255712
TI  - Regional intestinal permeability in rats of compounds with different
      physicochemical properties and transport mechanisms.
AB  - Because the absorption of orally administered drugs depends on intestinal
      permeability, we have investigated how absorptive capacity varies from the
      proximal to distal intestine in rats. The effective permeabilities of compounds
      with a range of physicochemical properties and different absorption mechanisms
      were estimated by use of a previously validated in-situ, single-pass perfusion
      model. The low colonic permeabilities of D-glucose and L-dopa indicate the
      absence or low capacity of the glucose- and amino-acid-transporters in this
      region. With the exception of the small and moderately lipophilic non-steroidal
      anti-inflammatory drug, naproxen, for which permeability was maintained
      throughout the intestine, the passive intestinal permeabilities for hydrophilic
      and lipophilic drugs were approximately twice as high in the jejunum and ileum as
      in the colon. These observations are in accord with those made in recent studies.
      However, the reasons for the high colonic permeability of non-steroidal anti
      inflammatory drugs, and results obtained in previous animal experiments
      demonstrating that the colon is the region of the intestine with the highest
      absorptive capacity were not fully clarified. These data show that the
      permeability to hydrophilic and lipophilic drugs decreases along the intestine,
      whereas it is maintained throughout the intestine for the small and moderately
      lipophilic naproxen. Further investigations are required to clarify the interplay
      between membrane composition, fluidity and permeability under various conditions
      in different absorption models.

PMID- 9255714
TI  - The ligand-binding site of buspirone analogues at the 5-HT1A receptor.
AB  - A three-dimensional model of the 5-HT1A receptor in man was constructed by
      molecular-modelling techniques and used to study the molecular interactions of a
      series of buspirone analogues with the 5-HT1A receptor by molecular-mechanical
      energy minimization and molecular-dynamics simulations. The receptor has seven
      trans-membrane alpha helices (TMHs) organized according to the electron-density
      projection map of visual rhodopsin, and includes all loops between TMHs and the N
      and C-terminal parts. The best fit between the buspirone analogues and the
      receptor model was obtained with the quinolinyl part of the ligand molecules
      interacting with amino acids in TMH6, the imide group interacting with amino
      acids in TMH2, TMH3 and TMH7, and the carbonyl groups hydrogen-bonded with Ser86
      and Ser393. The ligand-binding rank order deduced from the experimentally
      determined inhibition constant was reproduced by calculation of receptor-binding
      energies of the buspirone analogues. The models suggest that steric hindrance and
      repulsive forces between the receptor and the imide group of the buspirone
      analogues are the most important determinants of ligand-binding affinity for
      discriminating between these ligands.

PMID- 9255716
TI  - Indole alkaloids from Sickingia williamsii reduce the in-vitro effects of
      morphine withdrawal in the guinea-pig.
AB  - The effect of indole alkaloids from Sickingia williamsii Standl. (Rubiaceae) on
      the effects of morphine withdrawal have been examined in-vitro. All the indole
      alkaloids isolated from S. williamsii (10(-4), 5 x 10(-5) and 10(-5) M)
      significantly and in a concentration-dependent manner reduced the effects of
      morphine withdrawal on the guinea-pig ileum. The results suggest that these
      alkaloids might be potential anti-addictive agents.

PMID- 9255715
TI  - Antiplatelet effects of some aporphine and phenanthrene alkaloids in rabbits and
      man.
AB  - Two aporphines (boldine and laurolitsine) and five phenanthrene alkaloids
      (litebamine, secoboldine, N-cyanosecoboldine, N-methylsecoglaucine and N
      methylsecopredicentrine) were evaluated in-vitro for their ability to inhibit
      platelet aggregation. All seven alkaloids inhibited aggregation of rabbit
      platelets and inhibited the release of ATP induced by arachidonic acid and
      collagen in rabbit platelets. Those aggregations induced by platelet-activating
      factor (PAF), thrombin, U46619 and ADP were inhibited by the three N-substituted
      secoboldine derivatives only. Thromboxane B2 formation caused by arachidonic acid
      was also suppressed by these compounds. They did not affect the generation of
      [3H]inositol monophosphate caused by collagen, PAF and thrombin in the presence
      of indomethacin. Platelet cyclic AMP level was unaffected by litebamine, but was
      increased by N-methylsecoglaucine. Litebamine suppressed the secondary
      aggregation, but not the primary aggregation, induced by ADP and adrenaline in
      platelet-rich plasma from man, whereas N-methylsecoglaucine inhibited both
      primary and secondary aggregation. It is concluded that the antiplatelet effect
      of these seven aporphine and phenanthrene alkaloids is mainly a result of
      inhibition of thromboxane A2 formation; N-methylsecoglaucine has additional
      antiplatelet activity as a result of increasing the levels of platelet cyclic
      AMP.

PMID- 9255717
TI  - Interaction of local anaesthetics with histamine H1 receptors in guinea-pig
      ileum.
AB  - The interaction of amine local anaesthetics and related compounds with histamine
      H1 receptors was investigated in guinea-pig ileal longitudinal muscle.
      Quinacrine, chloroquine, tetracaine and procaine inhibited [3H]mepyramine binding
      to solubilized membrane from ileal muscle with pKi values of 5.27 +/- 0.11, 5.66
      +/- 0.01, 4.28 +/- 0.08 and 3.97 +/- 0.11, respectively. The pKB values obtained
      from the initial parallel shift of the dose-response curves for histamine in the
      presence of these drugs were 5.49 +/- 0.11, 6.14 +/- 0.09, 4.86 +/- 0.06 and 4.58
      +/- 0.06, respectively, in reasonable agreement with the pKi values. The combined
      dose-ratio test with both local anaesthetics and antagonist (mepyramine) present
      showed that tetracaine and procaine were competitive and chloroquine was
      partially competitive, but that quinacrine was not competitive at histamine H1
      receptors. These local anaesthetics inhibited histamine-induced desensitization
      in guinea-pig ileum. Receptor occupancy (%) by agonist decreased from 95.2
      (without inhibitor) to 73.9, 42.8, 35.9 and 33.9 in the presence of quinacrine,
      chloroquine, tetracaine or procaine, respectively, under the conditions where
      each inhibitor drug induced half maximum inhibition of desensitization. The
      results suggested that most of these local anaesthetics interacted competitively
      at histamine H1 receptors and inhibited desensitization through their
      antagonizing actions, whereas quinacrine interacted allosterically and inhibited
      desensitization through a separate action.

PMID- 9255718
TI  - Effect of chitosan on renal function in patients with chronic renal failure.
AB  - The effects of chitosan have been investigated on eighty patients with renal
      failure undergoing long-term stable haemodialysis treatment. The patients were
      tested after a control treatment period of 1 week. Half were fed 30 chitosan
      tablets (45 mg chitosan/tablet) three times a day. Ingestion of chitosan
      effectively reduced total serum cholesterol levels (from 10.14 +/- 4.40 to 5.82
      +/- 2.19 mM) and increased serum haemoglobin levels (from 58.2 +/- 12.1 to 68 +/-
      9.0 g L-1). Significant reductions in urea and creatinine levels in serum were
      observed after 4 weeks of chitosan ingestion. The feeling of physical strength,
      the appetite and the sleep of patients in the treatment group had improved
      significantly after 12 weeks of ingestion, compared with those of patients in the
      control group. During the treatment period, no clinically problematic symptoms
      were observed. These data suggest that chitosan might be effective treatment for
      renal failure patients, although the mechanism of the effect should be
      investigated further.

PMID- 9255719
TI  - Use of microdialysis for in-vivo monitoring of hydroxyl free-radical generation
      in the rat.
AB  - Free-radicals are reported to cause the tissue-damage associated with some toxins
      and diseases, yet there is no suitable method for routine in-vivo monitoring of
      these species. This paper introduces an in-vivo microdialysis technique in which
      the hydroxyl radical reacts with salicylate to generate dihydroxybenzoic acids
      (DHBA) which are measured by HPLC with electrochemical detection. When pargyline,
      a monoamine oxidase inhibitor, was infused into rat brain, the levels of DHBA
      increased markedly. When noradrenaline was administered to animals pre-treated
      with pargyline, DHBA levels increased markedly compared with the group treated
      with noradrenaline only. When the heart was subjected to 15-min regional
      ischaemia by occlusion of the left anterior descending coronary artery, levels of
      DHBA in heart dialysate were unchanged. Electrical stimulation of the stellate
      ganglion resulted in marked elevation of levels of DHBA the myocardial dialysate.
      Infusion of Fe2+ into rat liver resulted in increased formation of DHBA. When the
      intestine was rendered ischaemic for 10, 20 and 30 min, the highest DHBA level
      was obtained after 10-min ischaemia and the lowest after 30 min. These results
      confirm that free-radical production might make a major contribution at certain
      stages in the progression of the injury.

PMID- 9255720
TI  - A comparison of the standard approach and the NONMEM approach in the estimation
      of bioavailability in man.
AB  - There has recently been concern about confidence intervals calculated using the
      standard error of parameter estimates from NONMEM, a computer program that uses a
      non-linear mixed-effects model to calculate relative bioavailability (F), because
      of possible downward bias of these estimates. In this study an alternate
      approach, the log-likelihood procedure, was used to calculate the confidence
      intervals for F from NONMEM. These were then compared with those calculated using
      the standard error of the parameter estimates, the traditional NONMEM approach,
      and the standard model-independent method, to determine whether bias exists. By
      use of data from a single dose, open cross-over study of ibuprofen using 14
      healthy male volunteers, NONMEM was shown to give results consistent with those
      obtained using the standard model-independent method of analysis and could be a
      useful tool in the determination of F where conditions for using the standard
      method of analysis are not optimum. The width of the confidence interval for F
      using the log-likelihood procedure was narrower and non-symmetrical when compared
      with that obtained using the traditional NONMEM approach. The width of the
      confidence interval obtained using the traditional NONMEM method was similar to
      that from the standard approach, however the parameter estimate for F was higher
      than that obtained from the standard method. This could have been because of an
      outlier in the data set to which the standard approach is more sensitive. No
      downward bias was found in the confidence intervals from NONMEM. The
      bioavailability data set was of relatively low variability and more research with
      highly variable data is necessary before it can be concluded that the confidence
      intervals calculated from NONMEM can be used for hypothesis testing.

PMID- 9255721
TI  - Predictions of carbamazepine concentrations using a Bayesian program (PKS System,
      Abbott): a retrospective evaluation in an outpatient population.
AB  - This work evaluates the performance of a Bayesian program (PKS System, Abbott)
      for predicting carbamazepine concentrations in an outpatient population. The
      retrospective study involved 20 epileptic patients (12 adults and 8 children)
      receiving carbamazepine monotherapy orally. The program was used to predict
      measured serum levels after feedback of 0, 1 or 2 steady-state concentrations. A
      significant negative prediction bias was observed when no feedback concentration
      was used for estimation. However, the prediction bias (mean prediction error;
      m.e.) decreased as soon as one feedback concentration was used for estimation.
      Precision (mean absolute prediction error; m.a.e.) was significantly improved
      with one feedback concentration and was even better with two concentrations.
      Likewise, r.m.s.e. (root mean squared error; composite of bias and precision)
      regularly decreased when the number of feedback concentrations used was
      increased. Eleven percent of the estimates were unacceptable clinically
      (prediction error > 2 mg L-1) when 1 feedback concentration was used; less than
      3% were unacceptable when two concentrations were used. Thus the performance of
      the Bayesian dosing program is acceptable when two feedback concentrations are
      known, and seems able to help the clinician adjust carbamazepine dosage in an
      outpatient population.

PMID- 9255722
TI  - A T-helper-2 bias in decidua: the prostaglandin contribution of the macrophage
      and trophoblast.

PMID- 9255723
TI  - Progestin-dependent stimulation of the human leukemia inhibitory factor promoter
      in SKUT-1B uterine tumor cells.
AB  - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which is essential for
      implantation in rodents and is expressed during the progesterone-dominated
      secretory phase of the menstrual cycle in the human endometrium. However, the
      effect of progestin on the transcriptional regulation of the LIF promoter has not
      been studied so far. In the present study, we used a luciferase reporter plasmid
      bearing 666 bp of the human LIF promoter (hLIF666-Luc) to investigate the effects
      of progestin on the transcriptional regulation of LIF in SKUT-1B uterine tumor
      cells. Jurkat T-lymphoma cells were used for comparison. Since both cell lines
      are devoid of functional progesterone receptors (PR), we co-transfected the cells
      with hLIF666-Luc and an expression vector for the human PR form B (PR-B) or A (PR
      A). Addition of the progesterone agonist MPA (medroxy-progesterone acetate, 2.5 x
      10(-7) M) resulted in induction of LIF transcription only in SKUT-1B cells, while
      it had no effect in Jurkat cells. Both PR forms were effective in inducing the
      LIF promoter in SKUT-1B cells when activated by MPA. However, the induction
      through PR-A was inhibited more efficiently by the progestin antagonist RU 486.
      We next investigated the stimulatory effect of MPA in SKUT-1B cells on deletion
      constructs (h274LIF-Luc, h148LIF-Luc and H82LIF-Luc) and found that it is
      maintained on these fragments. Thus, 82 bp are sufficient to mediate this effect.
      Our results show that the human LIF promoter is active in uterine tumor cells,
      and that it is differentially regulated by progestin in cells of uterine and
      lymphoid origin.

PMID- 9255724
TI  - PGE2, but not TGF beta 2, in rabbit blastocoelic fluid regulates the cytotoxic
      activities of NK and LAK cells.
AB  - Spontaneous and induced fetal resorptions have been associated with the
      infiltration and activation of GM1-positive natural killer (NK)-like cells.
      Predominance of these cells in the decidua and their reduced lytic activity
      suggest that regulation of their killing activity could be important for the
      survival of the fetus. It has therefore been hypothesized that the embryo was
      regulating NK lytic activity. To test this hypothesis, human and rabbit
      lymphocytes were cultured with various concentrations of interleukin-2. Their
      ability to kill 51Cr-labelled NK and lymphokine-activated killer (LAK)-sensitive
      targets was assessed in the presence of rabbit blastocoelic fluid taken at day-12
      of pregnancy (BF D-12). BF D-12 dramatically suppressed the killing activity of
      NK and LAK cells. This effect was observed on K562 (NK-sensitive targets), P815
      cells (LAK-sensitive targets), and freshly isolated cells in rabbit trophoblastic
      cell preparation. Elimination of prostaglandin E2 (PGE2), but not transforming
      growth factor beta 2 (TGF beta 2) or 6 keto prostaglandin F1 alpha (6KPGF 1
      alpha), by affinity chromatography, completely abolished BF biological activity.
      These findings clearly suggest that PGE2 in BF regulates the killing activity of
      NK and LAK cells, and that the semiallograft embryo plays an active role in its
      own protection. To our knowledge, it is the first demonstration that PGE2 from
      the embryo inhibits NK and LAK cell lytic activity.

PMID- 9255725
TI  - CD106 (VCAM-1) in testicular immunoregulation.
AB  - The expression of CD18, CD49d/CD29, CD44, CD54 and CD106 was studied in the
      testis of normal mice at various ages, in the cryptorchid testis, in the testis
      of estrogen-treated mice and in the testis of non-obese diabetic (NOD) mice,
      using immunocytochemistry to see which of these lymphocyte and endothelial
      adhesion proteins may be involved in lymphocyte regulation in the testis. CD18-,
      CD49d/CD29-, CD44- and CD54-expressing cells were not found in the normal > 10
      week-old BALB/c mouse testis. Leydig cells expressed CD106 strongly at this age.
      In contrast to the > 10-week-old testis, only very few interstitial cells of the
      2-week-old normal mice expressed CD106. The expression of CD106 increased
      gradually with age so that at 6 weeks of age the expression of CD106 was moderate
      in the interstitial tissue. In the experimentally abdominal testis, CD106 was
      expressed in the interstitial tissue as strongly as in the contralateral scrotal
      testis. CD44- and CD18-expressing cells were occasionally present in the
      interstitial tissue of the abdominal testis, but not in the contralateral scrotal
      testis. CD54 was present in the epithelium of the ductuli efferentes. In the
      testis of the estrogen-treated mice, CD106 was expressed in the interstitial
      tissue as strongly as in the normal mice. Occasional CD44- and CD18-expressing
      cells were found in the testicular capsule. In the testis of adult NOD mice,
      CD106 was present in the interstitial tissue, but none of the other studied
      proteins. Immunoblotting of CD106 from the adult testis under reducing conditions
      demonstrated a single broad band with a M(r) of 51-65 kDa. This is a novel
      isoform of CD106. In a modified Stamper-Woodruff assay, lymphocytes bound to the
      testicular interstitial tissue. In co-incubations of native Leydig cells and
      lymphocytes, anti-CD106 antibodies prevented formation of Leydig cell-lymphocyte
      rosettes more than isotype-matched irrelevant control antibodies, suggesting that
      Leydig cell lymphocyte binding occurs through CD106-CD49d interactions. In
      lymphocyte cultures in the presence of anti-CD3, anti-CD28, the M(r) > 5 K
      fraction of testis extract (containing CD106 as shown by immunoblotting) and anti
      CD106 or control antibody, anti-CD106 did not consistently affect T cell 3H-TdR
      incorporation. The present results suggest that CD106 expressed by the Leydig
      cells may act as an adhesion-promoting molecule or a co-stimulatory factor for T
      cells migrating to the testis.

PMID- 9255726
TI  - Autoantibodies and infertility: a review of the literature.
AB  - The role that autoantibodies play in infertility remains uncertain. There are
      conflicting data regarding the prevalence of autoantibodies in women with
      endometriosis. Certainly no one has demonstrated an association between the
      presence of antibodies in women with endometriosis and infertility. Despite
      intensive study, there is also no consensus on a role of autoantibodies to the
      zona pellucida as a cause of infertility. Recently, much attention has been
      focused on autoantibodies and infertility particularly with regards to
      phospholipid antibodies and their effect on IVF success rates. The literature
      suggests that women with infertility have an increased prevalence of phospholipid
      antibodies compared to fertile women. However, the presence of these antibodies
      has not been associated with a worsened prognosis for IVF cycles. Many questions
      remain to be answered. What is the cause of this apparently increased prevalence
      of autoantibodies in infertile women? Do these autoantibodies cause infertility
      or are they merely associated with some other condition which is actually
      causitive? Finally, can treatment of autoantibodies improve pregnancy rates in
      infertile couples after IVF or other infertility treatments? The answers to these
      questions should be sought by carefully conducted trials with appropriate control
      groups. Subjecting patients to expensive testing and 'treatments' before these
      answers are known is not consistent with good scientific or medical practice.

PMID- 9255727
TI  - Polymerase chain reaction protocols for the detection of DNA from mucosal human
      papillomavirus types -6, -11, -16, -18, -31 and -33.
AB  - Individual types of human papillomaviruses (HPV) which infect mucosal surfaces
      have been implicated as the causative agents for carcinomas of the cervix, anus,
      penis, larynx and the buccal cavity, occasional periungal carcinomas, as well as
      benign anogenital warts. The identification of particular HPV types is thus
      important for: identifying patients with premalignant lesions who are at risk of
      progression to malignancy; epidemiological studies; studies of the natural
      history of these viruses; and even medico-legal cases of suspected sexual abuse
      of children. In this protocol we describe PCR assays for: the identification of
      DNA from the mucosal HPVs types -6, -11, -16, -18, -31 and -33; a consensus HPV
      PCR for detecting DNA from 20 characterised mucosal HPVs, as well as more than 25
      novel HPVs; and, for a control PCR for beta-globin.

PMID- 9255728
TI  - Rapid differentiation of vaccine strains and field isolates of infectious
      laryngotracheitis virus by restriction fragment length polymorphism of PCR
      products.
AB  - A procedure was developed for differentiation of vaccine strains and field
      isolates of infectious laryngotracheitis virus (ILTV) by restriction fragment
      length polymorphism (RFLP) of DNA fragments amplified from the genome of ILTV by
      polymerase chain reaction (PCR). RFLP patterns of viral thymidine kinase (TK)
      gene, glycoprotein C (gC) gene, glycoprotein X (gX) gene and ICP4 gene amplified
      from different ILT viruses were compared. The results showed that the vaccine
      strain of tissue-culture-origin (TCO) could be readily distinguished from other
      ILT viruses. Moreover, two out of the four field isolates could be differentiated
      from vaccine strains of chicken embryo origin (CEO); but the remaining two field
      isolates were identical to the CEO vaccine strains. These results suggested that
      both vaccine-like and vaccine-unlike ILT viruses were involved in the field
      outbreak of this disease, and that the PCR/RFLP procedure could serve as a fast
      and sensitive method for the detection and differentiation of vaccine strains and
      field isolates of ILT viruses.

PMID- 9255729
TI  - Comparative evaluation of five rapid methods for identifying subtype 1b and 2c
      hepatitis C virus isolates.
AB  - A panel of 61 HCV isolates belonging to five different subtypes were used to
      evaluate five methods for rapid typing of HCV RNA: an in-house type-specific
      polymerase chain reaction based on the core region (type-specific PCR), a
      commercial amplification of the core region followed by hybridisation to probe
      coated wells (DEIA), a commercial amplification of the 5'-UTR region followed by
      hybridisation to probes immobilised on strips (LiPA), an in-house restriction
      fragment polymorphism analysis of the 5'UTR (RFLP), and a commercial serological
      method using synthetic peptides from the NS4 region (serotyping). The correct
      viral type was identified in 90% of cases by DEIA, in 82% of cases by type
      specific PCR, in 80% of cases by LiPA and RFLP, and in 67% of cases by
      serotyping. Correct identification of the virus subtype was much less frequent
      and was beyond the performance characteristics of some assays. Major problems
      were found in the identification of isolates belonging to type 2. This was
      probably at least partly due to the fact that all type 2 isolates in the viral
      panel were of subtype 2c, which has been considered rare until recently.

PMID- 9255730
TI  - Induction of antibodies to plant viral proteins by DNA-based immunization.
AB  - DNA-based immunization is a promising new technique for generating antibodies in
      laboratory animals for diagnostic purposes in biological science. The main
      advantages are the elimination of time and labor and the technically demanding
      steps of antigen purification. The DNA sequence of the protein of interest,
      cloned in a suitable in vivo expression vector that is administered
      intramuscularly or intradermally, is sufficient to induce an immune response in
      animals. We report the induction of antibodies to tobacco mosaic virus (TMV) coat
      protein (CP) as a highly immunogenic structural protein and potato virus Y (PVY)
      P1 protein (P1) as a nonstructural protein. The appropriate nucleotide sequences
      were introduced in a mammalian expression vector (pSG5) and injected
      intramuscularly into New Zealand White rabbits (Oryctolagus cuniculus). By 10
      days post-injection (dpi) a specific immune response was detected against TMV-CP,
      while it took about 5 weeks for a response to PVY P1. In both cases the antibody
      titers were significantly above the corresponding pre-immune serum, however, they
      were considerably below the titer of the matching conventionally produced
      antiserum. To our knowledge, this is the first report of DNA-based immunization
      in order to generate antibodies to plant viral proteins, but further improvements
      are necessary to increase antibody titers before this promising new technique can
      be introduced broadly in plant science for diagnostic purposes.

PMID- 9255731
TI  - Evaluation of a quantitative double ELISA strategy for confirmation and
      differentiation of HIV infection.
AB  - The current HIV pandemic is complicated by the spread of distinct types and
      subtypes of HIV. The currently used conventional diagnostic tests have shown
      limitations in the detection of antibodies against all HIV-1 subtypes, as
      demonstrated by recent identification of HIV-1 subtype O. To evaluate
      quantitatively the diagnostic potential of a double ELISA strategy for the
      detection and partial differentiation of HIV-1, HIV-1 subtype O and HIV-2
      infections blood samples were examined at five different test centers: Blantyre,
      Malawi; Abidjan and Daloa, Ivory Coast; Yaounde, Cameroon; Munich, Germany. All
      tests results, including ELISA extinction values and Western blot profiles, were
      forwarded to Munich for final interpretation. An indirect anti-HIV-1/2 ELISA and
      a competitive anti-HIV-1 ELISA were used in combination for the initial screening
      of blood specimens. All anti-HIV positive and anti-HIV negative samples were
      subjected to immunoblot analysis. Independent of the diversity of the extinction
      profiles, and of the test manufacturer, the quantitative evaluation of the ELISA
      extinction values could define two extinction areas with a 100% predictive value
      for HIV-1 seropositivity and HIV seronegativity; extinction values > 2 by the
      indirect ELISA and < 0.2 by the competitive ELISA for an anti-HIV-1 subtype A to
      I positive result; extinction values < 0.2 by the indirect ELISA and > 1.0 by the
      competitive ELISA for an anti-HIV negative result. Additionally, the quantitative
      evaluation of the extinction profile provides partial information on the HIV-1
      subtype as far as the distinction in group M and group O is concerned. In
      conclusion, the quantitative evaluation of this double ELISA strategy can reduce
      the number of blood specimens that require additional confirmatory testing in
      developing countries and can be superior to the immunoblot method during early
      seroconversion.

PMID- 9255732
TI  - A solid-phase enzyme linked immunosorbent assay using monoclonal antibodies, for
      the detection of African swine fever virus antigens and antibodies.
AB  - An improved solid-phase enzyme linked immunosorbent assay (ELISA) using
      monoclonal antibodies was developed to detect an African swine fever virus
      protein (VP73) in pig samples. The use of monoclonal antibodies against VP73
      allowed a sensitive and specific sandwich ELISA. This assay detected a limiting
      antigen concentration of 0.05 microgram/ml of VP73, lower than the detection
      limit of 0.6 microgram/ml obtained by using polyclonal antibodies by the same
      ELISA. The whole virus particle was detected with this method to a limit of 2.3 x
      10(2) PFU/ml. At the same time, an indirect ELISA was developed to detect ASFV
      antibodies. The results also indicate that this method may be a useful technique
      for epidemiological surveys.

PMID- 9255734
TI  - A new RNA-friendly fixative for the preservation of penaeid shrimp samples for
      virological detection using cDNA genomic probes.
AB  - In situ hybridization analysis of shrimp histological sections, utilizing Taura
      syndrome virus (TSV) specific cDNA probes, is the most sensitive diagnostic
      technique presently available for the detection of this penaeid shrimp viral
      disease. However, false negative genomic probe results are obtained frequently
      from samples of Pacific white shrimp, Penaeus vannamei, that have been preserved
      with Davidson's AFA (acetic acid, formaldehyde, alcohol) fixative and that,
      otherwise, demonstrate pathognomonic TSV lesions by routine histology. This
      problem was linked to prolonged storage of shrimp samples in Davidson's fixative,
      which is highly acidic (pH approximately 3.5-4). Degradation of TSV genomic RNA
      was hypothesized to be due to either fixative- induced acid hydrolysis and/or
      acidophilic endogenous ribonuclease activity. Routine H and E histology and in
      situ hybridization analyses were conducted on equal numbers of TSV infected P.
      vannamei juveniles that were preserved for four different time periods (2, 6, 10
      and 14 days) with either Davidson's fixative or a new, near neutral (pH
      approximately 6.0-7.0), RNA-friendly fixative (R-F) that was developed by the
      authors. In situ hybridization assays were conducted with and without R Nase
      precautions and all of the samples tested contained moderate to severe TSV
      lesions by routine histology. Davidson's preserved samples produced weak TSV
      probe signals after 2 days fixation, but did not react with the probes in those
      samples that were stored for > 6 days in the fixative. In contrast, TSV was
      detectable by gene probe in all of the time treatment samples preserved with the
      new R-F fixative. Equivalent in situ hybridization results were obtained when the
      same samples were analyzed in the absence of RNase-free conditions. These
      findings suggest that TSV RNA is degraded when samples are stored in an acidic
      fixative, such as Davidson's, for more than 2 days and that this problem can be
      prevented through preservation of shrimp samples with R-F fixative. The efficacy
      of this new fixative is demonstrated and the results show that RNase-free
      conditions are not necessary for conducting TSV in situ hybridization analyses.

PMID- 9255733
TI  - Immunolocalization of the pseudorabies virus immediate-early protein IE180 by
      immunoperoxidase staining.
AB  - The immediate-early (1E) gene of pseudorabies virus (PRV) expresses immediately
      upon infection, a phosphorylated protein (immediate-early protein, IE180) that
      can transactivate viral other genes and plays an essential role in regulating
      viral gene expression. In order to detect and localize IE180 in infected cells
      early on, this gene was cloned for overexpression, and the expressed products
      were applied to generate specific antibodies against IE180 protein. Two
      recombinant expression plasmids pN and pNB were constructed by cloning the IE
      gene onto pET 30a(+) expression vector via NcoI and BamHI sites. Plasmid pN
      contains the 1.8-kb NcoI-NcoI fragment of IE gene coding for the N-terminus of
      616 amino acid residues, while pNB contains the 2.8-kb NcoI-Bam HI fragment
      coding for the rest of the IE180 protein. Both pN and pNB were transformed,
      respectively, into E. coli cells and produced large amounts of IE protein
      products during induction with 1 mM IPTG. The expressed IE proteins for pN and
      pNB were 60 kDa and 100 kDa in size, respectively. These expression products were
      purified and then used as antigens to immunize mice for preparing specific
      antibodies against PRV IE180 protein. The specificities of the mice immune sera
      were confirmed by their abilities to react with IE180 protein present in the PRV
      infected cells in the Western immunoblotting assay. Furthermore, immunoperoxidase
      staining of PRV infected cells undertaken with these antisera revealed the
      subcellular distribution of the IE proteins in the infected cells and also
      demonstrated their transportation from the cytoplasm to the nucleus during
      infection.

PMID- 9255735
TI  - Molecular characterization of HIV viruses generated after in vivo ligation.
AB  - During the course of infection, human immunodeficiency virus type 1 (HIV-1)
      displays wide genotypic and phenotypic differences. Construction of chimeric
      viruses is useful to determine the genotypic basis that underlies phenotypic
      variations, but the procedure is time-consuming. Previously, it has been shown
      that co-transfection of truncated hemi-genomic HIV-1 proviral DNA can lead to
      generation of full-length infectious virus. In the study of HIV phenotypes, using
      this technique, it is important to determine whether recombination between the
      two hemigenomes occurs without mutations. After co-transfection, progeny
      recombinant viruses replicated at the same rate as the control. We purified
      progeny viruses from culture supernatants and determined mutations at the
      recombination site. It appeared that correct in vivo ligation depended on the
      purity of DNA and the restriction site used. It also appeared that some of the
      mutations observed affect replication, as progeny viruses bearing one of these
      mutations disappeared during in vitro cultures, whereas other mutants did not.
      Although this technique is widely applied to generate chimeric viruses, the
      results should be evaluated with care, since mutations influencing the phenotype
      of the progeny viruses may have been introduced.

PMID- 9255736
TI  - Elimination of background signals in a modified polymerase chain reaction-based
      reverse transcriptase assay.
AB  - Three highly sensitive reverse transcriptase (RT) assays were recently published
      that are at least one million times more sensitive than conventional RT assays.
      These assays derive their high sensitivities through the ability to amplify the
      complementary DNA (cDNA) product of the RT reaction by the polymerase chain
      reaction (PCR). We describe a modified PCR-based RT (PBRT) assay that retains the
      high sensitivities of the original assays while reducing their inherent
      background signals. The background signal of the PBRT assay was found to be due
      to an intrinsic RNA-dependent DNA polymerase activity of the Taq DNA polymerase,
      the enzyme used for the PCR. It could be eliminated by inserting a ribonuclease
      digestion step prior to amplifying the cDNA product of the RT reaction by PCR and
      by using a thermostable DNA polymerase identified as having reduced RNA-dependent
      DNA polymerase activity. Comparable results were obtained using three RNA
      templates with two purified RT enzymes. This modified assay is capable of
      detecting reliably between 10 and 100 molecules of RT, which is equivalent to
      between 1 and 10 retrovirus particles.

PMID- 9255737
TI  - Inactivation of rotavirus by new polymeric water disinfectants.
AB  - Two new insoluble polymeric materials were evaluated for their efficacies in
      inactivating rotavirus in flowing water in a biocidal filter application. The two
      polymers are N-chloro and N-bromo derivatives of a poly-styrene hydantoin
      prepared from commercial poly-styrene. The studies were conducted for rotavirus
      in halogen demand-free water at pH 7.0, 25 degrees C and Environmental Protection
      Agency (EPA) Test Water no. 2 at pH 9.0, 4 degrees C which contained heavy
      halogen demand. The range of flow rates studied was 0.16-1.22 ml s-1
      corresponding to contact times in the range of 4-24 s. Both of the polymers were
      effective in inactivating rotavirus, the N-bromo derivative providing a 4-6 log
      reduction under the test conditions. The materials may be useful as supplemental
      filters for hand-held water purification units.

PMID- 9255738
TI  - Quantification of HIV-1 viral RNA and proviral DNA by isotopic competitive PCR.
AB  - A quantitative isotopic competitive PCR (icPCR) assay was established using 32P
      labeled primers targeting the HIV-1 gag gene followed by quantification using a
      phosphoimager. The detection limit varied from 3 to 10 molecules of DNA and 10 to
      100 molecules of RNA per reaction. The icPCR quantification of HIV-1 DNA copies
      correlated well with the cell number of 8E5/LAV cells bearing a single provirus
      (r2 = 0.95). Provirus quantification was applied to overnight infected donor
      PBMCs, thereby determining infectious virus titres in culture supernatants as a
      rapid alternative to limiting dilution culture. Parallel quantification of the
      HIV-1 RNA indicated the infectious virus fraction to be 0.3%. In 39 HIV-1
      infected patients with clinical stages A (n = 17), B (n = 15), and C (n = 7), the
      HIV-1 RNA in the plasma was determined ranging from 100 to 90600 RNA copies/ml.
      The results of icPCR and a commercial assay (ROCHE Amplicor HIV-1 Monitor)
      correlated well (r = 0.97). In 13 additional patients, the plasma viral load per
      ml was compared with the proviral load per 10(6) PBMC showing a viral excess of
      10-1000-fold (mean of 85, r = 0.7, P < 0.01). It is concluded that icPCR is
      suitable for the measurement of proviral and viral load in experimental and
      clinical settings.

PMID- 9255740
TI  - Reactivity and amplification efficiency of the NASBA HIV-1 RNA amplification
      system with regard to different HIV-1 subtypes.
AB  - In view of the genetic diversity of the human immunodeficiency virus Type 1, we
      assessed the sensitivity and quantification efficiency of the HIV-1 RNA NASBA
      amplification system with respect to different HIV-1 subtypes and recombinants.
      Twenty cell culture supernatants representing 17 HIV-1 group M and 3 group O
      strains were tested, and NASBA RNA loads were compared with results obtained with
      a RT-PCR based HIV-1 RNA quantitation method, with p24-antigen concentrations and
      with the infective dose. The current HIV-1 RNA NASBA seemed suitable to
      quantitate representatives of different HIV-1 M subtypes. Differences between
      NASBA and RT-PCR loads were observed for certain HIV-1 M strains. Significantly
      lower RT-PCR loads were measured for most gag A, gag B and gag F strains, whereas
      NASBA detected lower copy numbers in 1 gag H strain and 1 gag H/env G
      recombinant. NASBA was not able to quantify 1 HIV-1 group M recombinant. Some of
      these differences could be explained by the presence and position of mismatches
      with primers. HIV-1 group O strains were not detectable by both RNA amplification
      methods. A firm correlation was not observed between the measured RNA loads and
      either the p24-antigen concentration or the infective dose.

PMID- 9255741
TI  - Detection of transmissible gastroenteritis virus by RT-PCR and differentiation
      from porcine respiratory coronavirus.
AB  - An RT-PCR method was developed that amplified genetic material from the 5' end of
      the S protein gene of both transmissible gastroenteritis virus (TGEV) and porcine
      respiratory coronavirus (PRCV), but discriminated between the two by the size of
      the product generated. A number of restriction endonuclease enzymes were assessed
      for recognition of the amplicons so produced. The assay was shown to detect viral
      RNA from all of the 26 different TGEV and PRCV isolates examined, covering a
      period from 1946 to 1996. Detection of TGEV in clinical specimens was possible
      using a spin column method to extract RNA and sensitivity was compared to virus
      isolation and antigen detection ELISA. The method could provide a means of
      confirming positive results from immunological screening tests such as FAT and
      ELISA, reducing the need for virus isolation and convalescent serology.

PMID- 9255742
TI  - Focus luminescence assay: macroscopically visualized foci of human
      cytomegalovirus and varicella zoster virus infection.
AB  - The plaques or foci of certain viruses due to their small size have to be counted
      microscopically, e.g., human cytomegalovirus (HCMV). The focus luminescence assay
      (FLA) described below generates macroscopic images as a result of the
      magnification due to scattered emitted light, and provides a hard copy using
      autoradiography or video imaging. Foci are detected according to an
      immunohistochemical protocol with horseradish peroxidase or alkaline phosphatase
      antibody conjugates which convert substrate into a luminescent product. Detection
      of varicella zoster virus (VZV) foci developed with a specific substrate-enhancer
      combination was so sensitive that 20-times lower primary antibody concentrations
      were effective than those required for conventional immunohistochemical staining.
      This method for HCMV and VZV may allow quantitative infectivity and focus
      reduction assays for viruses which produce little or no CPE.

PMID- 9255739
TI  - Green fluorescent protein expressed by recombinant pseudorabies virus as an in
      vivo marker for viral replication.
AB  - We isolated and characterized a pseudorabies virus (PrV) mutant expressing an
      engineered green fluorescent protein (GFP) optimized for expression in human
      cells. The GFP DNA was inserted in the non-essential glycoprotein G (gG) gene of
      the attenuated PrV strain Bartha. The coding sequence was cloned in frame behind
      the first seven codons of the gG gene under control of the strong gG promotor. On
      excitation with blue light, live cells infected with the recombinant PrV B80eGFP
      exhibited bright fluorescence when examined microscopically using filters for
      FITC fluorescence. In fixed samples detection sensitivity was increased by
      immunofluorescence using an anti-GFP antibody. Specifically labelled PrV mutants
      have been used successfully as transsynaptic circuit tracers for definition of
      central command neurons in the brain (Jansen et al., 1995. Central command
      neurons of the sympathetic nervous system: basis of the fight-or-flight response.
      Science 270, 644-646). Availability of this recombinant allows the study of even
      more complex interactions using differentially labelled PrV mutants, and provides
      a means to monitor viral replication and spread without destruction of the cell.

PMID- 9255743
TI  - The consequences of longevity.

PMID- 9255745
TI  - Womens attitudes and knowledge about the climacteric period and its treatment. A
      Swedish population-based study.
AB  - OBJECTIVES: The aim of the study was to investigate womens knowledge and
      attitudes about the menopause and hormone replacement therapy (HRT). MATERIAL AND
      METHODS: Women aged 46, 50, 54, 58 and 62 years, born on uneven days, resident in
      Goteborg, Sweden (n = 5.990) were invited by letter to complete a questionnaire
      concerning the menopause and HRT. RESULTS: The response rate was 76% (n = 4504).
      Current estrogen use was reported by 21%. Another 20% had stopped estrogen use
      e.g. because of a fear of cancer (9%) or other side-effects (14%). The most
      common reasons to refrain from HRT were minor climacteric symptoms (27%), fear of
      cancer (9%) or side-effects (15%) and the opinion that the menopause is a natural
      process (20%). A majority (67%) preferred HRT without withdrawal bleedings,
      especially elderly women (80%). Thirty-five per cent could accept life-long HRT
      if treatment was free from withdrawal bleedings. Almost 70% received their
      information about the menopause and HRT from a physician. Forty-five percent of
      the women considered the menopause to be a relief. Approximately 60% had a
      regular sex-life. The most common reasons for not having a regular sex-life were
      irrespective of the womans age, the absence of a partner (43%). Loss of sexual
      desire (29%) or partners loss of desire (12%), both of which showed an increase
      with age, were other reasons given. Only 8% of the total population had no sexual
      activity because of vaginal dryness but in the oldest cohort (62 years old) 32%
      gave this as a reason. CONCLUSION: Physicians require more time for counselling
      of patients about the menopause and HRT. Many women refrain from therapy because
      of fear and misconceptions. To achieve better long-term compliance especially in
      elderly women the use of 'non-bleeding' regimes requires further attention.

PMID- 9255744
TI  - Does estrogen replacement therapy reduce the risk of fatal breast cancer in
      postmenopausal women?

PMID- 9255746
TI  - Validity and reproducibility of self-reported age at menopause in women
      participating in the DOM-project.
AB  - OBJECTIVES: To study validity and reproducibility of self reported age at
      menopause. METHODS: Subjects were 1003 and 4892 Dutch women respectively aged 58
      73, who participated in a population-based breast cancer screening project. The
      median time since menopause was 7 years for the validity study. The time span
      between the two questionnaires in the reproducibility study was 7-9 years.
      RESULTS: Of the women with a natural menopause, 70% recalled their age at
      menopause correctly to within one year. For women with a surgical menopause this
      percentage was 80%. The validity decreased with increasing number of years since
      menopause. Reproducibility to within one year was 71% for women with a natural
      menopause and 79% for women with a surgical menopause; 95% of the women were
      consistent in reporting whether they had had a natural or a surgical menopause.
      CONCLUSIONS: As a consequence of this misclassification, the effect of age at
      menopause may be underestimated in studies relating self reported age at
      menopause to disease occurrence or mortality.

PMID- 9255747
TI  - A clinical and urodynamic study of patients with varying degrees of cystocele.
AB  - OBJECTIVE: To assess urodynamic alterations in patients with varying degrees of
      cystocele but without prolapse of the uterus, rectocele and/or enterocele.
      PATIENTS AND METHODS: Between September 1993 and June 1995 we examined 83
      patients with varying degrees of isolated cystocele. All subjects were questioned
      about their medical history and underwent urogynaecological examination and
      urodynamic tests. RESULTS AND CONCLUSIONS: In our study there were no cases of
      pure urge incontinence nor were there any normal urodynamic situations; genuine
      stress incontinence was the most frequent urinary disorder. Moreover patients
      with grade 3-4 cystocele on the Baden-Walker scale had more difficulty in voiding
      than subjects with milder forms of cystocele. In fact the maximum and average
      flow rates of the former tended to decrease, flow and voiding times were longer
      and acceleration of flow rate were significantly lower. The maximum urethral
      closure pressure tended to diminish with an increase in the duration of
      menopause, whereas the pressure transmission ratio tended to decline
      significantly with an increase in cystocele severity. In conclusion, even when
      cystocele is the only alteration in pelvic statics, it determines significant
      urodynamic changes that must be carefully assessed so as to optimize the choice,
      mode and time of surgical, rehabilitative or pharmacological intervention.

PMID- 9255748
TI  - Comparison of transvaginal ultrasonography and endometrial biopsy in endometrial
      surveillance in postmenopausal HRT users.
AB  - OBJECTIVES: To compare transvaginal ultrasonography with histological findings in
      endometrial evaluation of postmenopausal women using hormone replacement therapy
      and to evaluate endometrial safety of three hormone replacement therapy regimens.
      METHODS: In a randomized, comparative study in postmenopausal women, endometrial
      safety was evaluated using (1) no hormone replacement therapy, (2) oral
      micronized 17 beta-estradiol/oral sequential dydrogesterone, (3) transdermal 17
      beta-estradiol/oral sequential dydrogesterone, or (4) oral tibolone. 85 Non
      hysterectomised subjects underwent transvaginal ultrasonography immediately
      before Pipelle biopsy at baseline and subsequently after 12 and 24 months.
      Endometrial thickness and uterine dimensions were determined by transvaginal
      ultrasonography, and endometrial thickness (double-layer) was compared with
      biopsy results. RESULTS: Endometrial evaluation was conveniently performed by
      transvaginal ultrasonography, and endometrial thickness correlated well with
      biopsy findings. If endometrial thickness was < 5 mm, the endometrial biopsy
      sample was either inactive/atrophic or insufficient for histopathological
      diagnosis. Hyperplastic or malignant changes were not reported. After 24 months,
      endometrial thickness was increased both in the oral (P < 0.001) and transdermal
      (P < 0.001) 17 beta-estradiol/dydrogesterone groups, whereas with tibolone the
      change in endometrial thickness was not different from controls. CONCLUSION:
      transvaginal ultrasonography of the endometrium reliably predicts the
      histological picture in hormone replacement therapy users. Using 5 mm endometrial
      thickness as cut-off point, more than 75% of biopsies could be avoided. All three
      hormone replacement therapies were safe with respect to the endometrium. With
      sequential 17 beta-estradiol/dydrogesterone the expected progestogen-induced
      secretory pattern was observed, whereas endometrial histology under tibolone
      closely mimicked the natural atrophic postmenopausal state.

PMID- 9255749
TI  - Hormone replacement therapy and some salivary antimicrobial factors in post- and
      perimenopausal women.
AB  - OBJECTIVES: The effect of hormone replacement therapy (Cyclabil) on non
      immunoglobulin (peroxidase) and immunoglobulin (total IgA, IgG, IgM)
      antimicrobial factors as well as on total protein and microorganisms in whole
      saliva was assayed in 19 postmenopausal and 8 perimenopausal women. METHODS:
      Paraffin-stimulated whole saliva was collected before as well as 3 and 5 months
      after the onset of the treatment. Time- and group-related differences between
      post- and perimenopausal women were analyzed. RESULTS: Peroxidase and total
      protein output per min increased significantly (P = 0.004 and 0.001) during the
      treatment in both groups. No significant time- or group-related differences in
      the mean concentrations of the respective variables were found. The mean
      concentrations of salivary IgA and IgG showed a significant time-related decrease
      in both groups (P = 0.012 and 0.010). Salivary IgM concentration in
      perimenopausal women also showed a significant time-related decline (P = 0.017)
      and the difference in changes of salivary IgM between the two groups was
      significant (P = 0.033). Total IgA output per min increased in perimenopausal
      whereas it decreased in postmenopausal women (interaction; P = 0.021). Hormone
      treatment had no effect on the amount of salivary bacterial floras. CONCLUSIONS:
      The composition of saliva in post- and perimenopausal women was found to be
      estrogen-dependent. The second finding was that all women participating in the
      study reported a sense of enhanced oral well-being including relief of oral
      dryness.

PMID- 9255750
TI  - Systemic therapy with estrogen or estrogen with progestin has no effect on skin
      collagen in postmenopausal women.
AB  - OBJECTIVES: To investigate the effect of estrogen alone or combined with
      progestin on the amount and synthesis of skin collagen in postmenopausal women.
      METHODS: Forty-three early postmenopausal women were enrolled into this open, non
      randomized parallel-groups study. Fifteen women received a continuous oral dose
      of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate daily and 14
      women an oral dose of 2 mg estradiol valerate daily. Fourteen subjects served as
      controls. The histology and type I and III procollagen immunohistochemistry of
      the skin, skin thickness, the amount of total collagen determined by a
      colorimetric method and the synthesis of type I and III collagens determined by
      analysing procollagen propeptides in the suction blister fluid were studied
      before the treatment and at 6 and 12 months. The proportional area of elastic
      fibers and the thickness of the epidermis were assessed from the sections
      obtained before the treatment and at 12 months, with computerized image analysis.
      RESULTS: Skin thickness, the amount and rate of collagen synthesis, the
      proportional area of elastic fibers and the thickness of the epidermis were not
      affected by either 17 beta-estradiol and 1 mg of norethisterone acetate or 2 mg
      of estradiol valerate. No histological or immunohistological changes were
      detected in the skin specimens during the 12-month treatment period compared to
      the baseline or to the skin specimens of the control group. CONCLUSIONS: A 1-year
      treatment with systemic estrogen alone or combined with progestin does not change
      the amount of collagen or the rate of collagen synthesis in postmenopausal women.

PMID- 9255751
TI  - Hemodynamic effects of transdermal estradiol alone and combined with
      norethisterone acetate.
AB  - A 24 weeks, randomized, two-period, placebo controlled study was conducted to
      compare the effects of continuous transdermal 17 beta-estradiol replacement
      therapy (0.05 mg/day once a week) with placebo on systemic hemodynamics and blood
      pressure in postmenopausal women. Twenty-nine postmenopausal women (47-62 years)
      free of hormone replacement therapy were randomized in two groups; group 1
      received estradiol patches for the first 12 weeks and placebo patches for the
      second, and group 2 received the same treatments in the reverse order. The effect
      of combined estradiol plus oral norethisterone acetate (NETA) 1 mg was also
      evaluated in the subset of women with intact uteri (n = 24). Crossover analysis
      showed that stroke volume and cardiac output were significantly higher (P < 0.05)
      and blood pressure was significantly lower (P < 0.05) with estradiol,
      irrespective of the order in which the treatments were administered. Although
      correlations between plasma estradiol levels during active treatment and
      hemodynamic changes were not significant, hemodynamic changes were significantly
      greater above 63 pg/ml than below this level (P < 0.05). Oral norethisterone
      acetate administration either during transdermal placebo or estradiol arms tended
      to modify systemic hemodynamics in the same direction than estradiol but the
      changes did not attained statistical significance. In summary compared with
      placebo, transdermal 17 beta-estradiol, replacement to postmenopausal women,
      increased cardiac output and decreased blood pressure. Although the average
      magnitude of changes was small, the results suggest that plasma estradiol levels
      could be a source of individual variability in the hemodynamic response. Oral
      NETA administration tended to enhance rather than reverse the estradiol-induced
      changes.

PMID- 9255752
TI  - Changes in bone collagen markers and in bone density in hormone treated and
      untreated postmenopausal women.
AB  - OBJECTIVE: This study aims to compare bone mineral density measurements (BMD),
      pyridinium crosslink levels and pyridinium crosslink levels in untreated and
      hormone treated postmenopausal women. METHODS: A cross-sectional study comparing
      biophysical (BMD) and biochemical (pyridinium crosslink and PCICP) parameters in
      a group of untreated postmenopausal women (n = 145) to a group of postmenopausal
      women on hormone replacement therapy (HRT) (n = 92). RESULTS: Untreated
      postmenopausal women compared to postmenopausal women on HRT had higher
      Osteoblastic and Osteoclastic activity. Procollagen I C-end terminal peptide
      (PCICP) was 11.3% lower in the women on HRT compared to controls whilst
      crosslinks were 27.2% lower than in controls. This seems to indicate that women
      on HRT had a bone balance that was higher compared to the control group (15.9%).
      The difference in bone density of L2-L4 between the two groups was (16.1%).
      CONCLUSIONS: This study seems to indicate that postmenopausal women receiving HRT
      readjust their bone remodelling so that although osteoblastic function is
      reduced, there is a much greater deduction in osteoclastic function and this
      results in an overall higher bone mass observed in the BMD of women on HRT.

PMID- 9255753
TI  - Plasma estradiol concentrations and pharmacokinetics following transdermal
      application of Menorest 50 or Systen (Evorel) 50.
AB  - OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen
      replacement therapy (ERT) systems designed to release 50 micrograms 17 beta
      estradiol/day, two studies were performed in healthy postmenopausal volunteers.
      METHODS: Both studies had a cross-over design and incorporated a 1-week wash-out
      period between treatments. In the first study, Menorest 50 and Systen 50 (Evorel
      50) were compared over four days of application in 30 women. In the second, 13
      women wore each of the two systems for a total of 12 days each (three patches
      each for 4 days), and comparison was made during the third patch period (steady
      state, between days 8 and 12). Plasma 17 beta-estradiol levels were assayed using
      specific direct radioimmunoassays, and pharmacokinetic parameters were calculated
      by standard methods. All the samples of the first study were re-analysed using a
      different radioimmunoassay and the results of both assays were compared. RESULTS:
      In both studies, plasma 17 beta-estradiol levels rose at a comparable rate and
      reached similar peak levels with each of the two formulations. Levels then
      remained relatively constant throughout both evaluation periods with Menorest 50,
      but began to decline after 12 hours in the first study and after 30 h under
      steady state conditions in the second study with Systen 50. The difference
      between the two products was statistically significant in both studies. Analysis
      of pharmacokinetic parameters confirmed the greater bioavailability of Menorest
      50. In addition, 17 beta-estradiol levels remained within the suggested
      therapeutic ranges for relief of acute symptoms and protection against
      osteoporosis for longer periods of time with Menorest 50 than with Systen 50.
      CONCLUSION: Since the acute efficacy, long-term protective effects, side effects
      and risks associated with ERT may depend on critical threshold plasma levels,
      much attention should be paid to the pharmacokinetic profiles of different
      formulations. The comparison of these two different radioimmunoassays
      demonstrates the comparability of their results.

PMID- 9255754
TI  - Effect of tibolone on postmenopausal women with myomas.
AB  - OBJECTIVE: The aim of this study is to assess the effect of Tibolone (Livial) on
      uterine fibroids in postmenopausal women. METHODS: This study included 40
      naturally postmenopausal women with at least one uterine fibroid measuring > 20
      mm. All of theme were scanned by transvaginal ultrasonography. Patients were
      randomized into two groups. Group A (n = 20) were treated with Tibolone 2.5 mg
      daily for 1 year and group B (n = 20) did not received therapy. The size of the
      uterine fibroids was reevaluated on the end of the treatment. RESULTS: No
      statistically significant difference was found in the mean volume of fibroids
      before and after treatment with Tibolone. The administration of Tibolone resulted
      in an increase of fibroid volume in three patients, whereas it remained constant
      in the majority of the patients (70%) and decreased in three patients.
      CONCLUSIONS: Our results suggest that treating menopausal symptoms with Tibolone
      does not affect preexisting asymptomatic uterine fibroids.

PMID- 9255755
TI  - Cell aging in vivo and in vitro.
AB  - It has become a staple assumption of biology that there is an intrinsic fixed
      limit to the number of divisions that normal vertebrate cells can undergo before
      they senesce, and this limit is in some way related to aging of the organism. The
      notion of such a limited replicative lifespan arose from the often repeated
      observation that diploid fibroblasts cannot proliferate indefinitely in monolayer
      culture, and that the number of divisions before senescence is directly related
      to the in vivo lifespan of different species. The in vitro evidence is countered
      by estimates that the number of cell divisions in some organs of rodents and man
      are one or more orders of magnitude higher than the in vitro limit, with no
      indication of the degenerative changes seen in culture. Serial transplantation
      experiments in animals also exhibit many more cell divisions than the in vitro
      studies, with some indicating an indefinite replicative lifespan. I present
      evidence that vertebrate cells are severely stressed by enzymatic dispersion and
      sustain cumulative damage during serial subcultivations. The evidence includes
      large increases in cell size and its heterogeneity, reductions in replicative
      efficiency at low seeding densities, appearance of abnormal structures in the
      cytoplasm, changes in metabolism to a common cell culture type, continuous loss
      of methyl groups and reiterated sequences from DNA, and a constant rate of
      decline of growth rate with passage. This evidence is complemented by the
      reduction induced in the replicative life span of diploid cells by a large array
      of treatments which have different primary targets in the cells. The most
      consistent and general observation of cell behavior in aging animals, with only a
      few exceptions, is a reduction in the rate of cell proliferation. This reduction
      is perpetuated when the cells are grown in culture, indicating it is an enduring
      and intrinsic property of the cells rather than a systemic effect of the aging
      organism. A similar heritable reduction in growth rate can be induced in
      established cell lines by prolonged incubation at quiescence. The reduction can
      be exaggerated by subculturing the quiescent cells under suboptimal conditions,
      just as the effects of age are exaggerated under stress. The constant decline of
      growth rate that occurs during serial passage of diploid cells may represent a
      similar decay of cell function. I propose that the limit on replicative lifespan
      is an artifact that reflects the failure of diploid cells to adapt to the trauma
      of dissociation and the radically foreign environment of cell culture. It is,
      however, a useful artifact that has given us much information about cell behavior
      under stressful conditions. The overall evidence indicates cell in vivo
      accumulate damage over a lifetime that results in gradual loss of differentiated
      function and growth rate accompanied by an increased probability for the
      development of cancer. Such changes are normally held to a minimum by the
      organized state of the tissues and homeostatic regulation of the organism. The
      rejection of an intrinsic limit on the number of cell divisions eliminates the
      need for a cellular clock, such as telomere length, that counts mitoses. I offer
      a heuristic explanation for the gradual reduction of cell function and growth
      capacity with age based on a cumulative discoordination of interacting pathways
      within and between cells and tissues. I also make a case for the use of
      established cell lines as model systems for studying heritable damage to cell
      populations that simulates the effects of aging in vivo, and represents a
      relatively unexplored area of cell biology.

PMID- 9255756
TI  - Insulin receptors in mouse brain: age-related modifications are corrected by
      thymus graft.
AB  - Recently, we have shown that insulin receptors (InsRs) in the brain undergo
      impairment with aging, as happens for other receptors such as alpha- and beta
      adrenoceptors. Age-related alterations of adrenoceptors, which are modulated by
      brain InsRs, are not definitive as they can be recovered by a thymus graft. In
      this study we verified the possibility that the thymus graft can also recover the
      age-dependent modifications of brain InsRs. InsR characteristics were assayed in
      a group of 27 months old Balb/c-nu mice grafted with a neonatal thymus, under
      renal capsule, one month before the animals were killed. Another two groups of
      young (3 months) and old (27 months) mice were used as controls. A two-sites
      model analysis of receptor data confirmed the age-dependent decrease of InsR
      density previously observed in the high affinity population. Furthermore, a
      statistically significant recovery of this impairment was shown in thymus grafted
      animals. The low affinity receptor subset also showed some differences among the
      three animal models; however, they were not statistically significant. Thymus
      graft induced recovery of the age-related changes found in brain InsRs, together
      with the similar one observed on the adrenergic system, calls for deeper studies
      of their interaction and the role they can play on aging processes.

PMID- 9255757
TI  - Physiological basis for long life span.
AB  - A collection of clinical data is reported on nonagenarians in comparison to an
      'average' population of younger age. The results of these clinical data indicated
      that a vital physiological basis for long life span probably existed. The basis
      include a better micro-blood-flow state, a better cardiac, immune (nature killer
      cell activity), adrenocortical, hepatic and renal function, and a higher level of
      high density lipoprotein cholesterol. It is suggested that the method, including
      Chinese traditional medicine, to improve the micro-blood-flow, nature killer cell
      activity, high density lipoprotein cholesterol and vital organ function may be
      beneficial for life preservation and aging retarding.

PMID- 9255758
TI  - Expression and catalytic activities of protein tyrosine kinases (PTKs) Fyn and
      Lck in peripheral blood T cells from elderly humans stimulated through the T cell
      receptor (TCR)/CD3 complex.
AB  - Optimal signal transduction through the T cell receptor (TCR)/CD3 complex
      requires the coordinated activities of protein tyrosine kinases (PTKs) Fyn and
      Lck in addition to protein tyrosine phosphatases (PTPases) such as CD45. Although
      T cells stimulated with anti-CD3 monoclonal antibodies (mAb) exhibit age-related
      reductions in tyrosine phosphorylations of cellular proteins, it is unknown if
      the reduction represent abnormalities in PTKs or PTPases. In the current studies,
      immune complex kinase assays showed that the stimulation of peripheral blood T
      (PBT) cells from young humans with cross-linked anti-CD3 epsilon mAb OKT3 induced
      increased Fyn catalytic activity while anti-CD3 stimulation failed to induce
      significant increases in Lck activation. By contrast, Fyn activation in anti-CD3
      stimulated PBT cells from a substantial proportion of elderly humans was reduced
      compared to anti-CD3 stimulated PBT cells from young humans. Also, we failed to
      find any increase in anti-CD3 stimulation of Lck activity in PBT cells from
      elderly subjects that could compensate for the decline in Fyn activity. However,
      no age-related alterations were detected in PBT cell expression of Fyn or Lck
      that might contribute to the changes in enzymatic activity. The results of other
      experiments demonstrated that the functional activities of PTPases in PBT cells
      from elderly subjects were equivalent to PBT cells from young subjects. These
      observations suggest that aberrant regulation of TCR/CD3 coupled PTKs may
      contribute to the age-related defects in signaling cascades and immune
      responsiveness of human T cells.

PMID- 9255759
TI  - Contribution of IL-1 beta to the enhancement of Campylobacter rectus
      lipopolysaccharide-stimulated PGE2 production in old gingival fibroblasts in
      vitro.
AB  - Campylobacter rectus is associated with adult periodontitis. We previously
      reported that C. rectus lipopolysaccharide (LPS)-stimulated prostaglandin E2
      (PGE2) production in old cells of human gingival fibroblasts (HGFs) is higher
      than that in young cells. The present study examined whether an enhancement of C.
      rectus LPS-stimulated interleukin (IL)-1 beta production in old HGFs contributed
      to the increased production of PGE2. LPS was prepared from C. rectus ATCC33238.
      HGFs were established from healthy gingiva in three patients, aged 10-12 years.
      Cellular aging in culture was determined with increasing doubling. The cultured
      cells were treated with LPS (0.01-10 micrograms/ml), and the amount of IL-1 beta
      in the medium was measured after a 24 h incubation. The LPS-stimulated IL-1 beta
      production in each old cell (corresponding to 57-67% of complete life-span) was
      increased (1.6-2.6 times) compared to that in the young cells (corresponding to
      17-20% of the life-span). The IL-1 beta mRNA synthesis in the presence of LPS in
      the old cells was higher than that in the young cells. The enhancement of LPS
      stimulated PGE2 production was inhibited by anti-IL-1 beta antibody and by IL-1
      receptor antagonist. These findings suggest that the greater ability of old cells
      to produce PGE2 in response to C. rectus LPS is due to their greater level of IL
      1 beta.

PMID- 9255760
TI  - Internalization of human rhinovirus 14 into HeLa and ICAM-1-transfected BHK
      cells.
AB  - Virus adsorption and uptake of human rhinovirus 14 (HRV14) were studied with HeLa
      cells and baby hamster kidney (BHK) cells which were transfected with the HRV14
      receptor intercellular adhesion molecule-1 (ICAM-1). Transmission electron
      microscopy of HeLa cells revealed that HRV14 was internalized via clathrin-coated
      pits and -coated vesicles. A minority of virus particles also used uncoated
      vesicles for entry. The internalization showed the characteristics of receptor
      mediated endocytosis. Presence of the carboxylic ionophore monensin inhibited
      viral uncoating, indicating a pH-dependent entry mechanism. The expression of
      ICAM-1 on the surface of the ICAM-1 transfected baby hamster kidney cells (BHK
      ICAM cells) allowed extensive virus adsorption and internalization through
      membrane channels. Virus particles were lined up in these channels like pearls on
      a string, but did not induce a productive infection. Although ICAM-1 was
      expressed to the same degree on BHK-ICAM and HeLa cells, HRV14 induced neither
      viral protein and RNA syntheses nor infectious virus progeny in BHK-ICAM cells.
      ICAM-1 on the transfected BHK cells was a functional active receptor as it
      rendered these cells permissive to coxsackievirus A21. These results suggest that
      HRV14 uptake into BHK-ICAM cells is blocked directly in or shortly after its
      final step of internalization, the uncoating. Our findings underline that the
      receptor ICAM-1 determines virus uptake into cells, however, is not sufficient to
      confer susceptibility of BHK cells to HRV14 infection.

PMID- 9255761
TI  - HIV-1-infected myelomonocytic cells are resistant to Fas-mediated apoptosis:
      effect of tumor necrosis factor-alpha on their Fas expression and apoptosis.
AB  - To get insight into the involvement of tumor necrosis factor-alpha (TNF-alpha)
      and Fas (CD95) ligand in apoptosis (programmed cell death) of
      monocyte/macrophages in HIV-1-infected individuals, various T cell and
      myelomonocytic cell lines, including the HIV-1-infected clones OM-10.1 and U1
      cells, were cultured in the presence of either TNF-alpha alone, anti-Fas agonist
      monoclonal antibody (Fas-mAb) alone, or their combinations. TNF-alpha moderately
      decreased the viability of myelomonocytic cell lines in a dose-dependent fashion
      (1-100 ng/ml). Unlike HIV-1-infected T cell lines, the viability of OM-10.1 and
      U1 cells was not affected by the treatment with Fas-mAb alone at concentrations
      up to 1,000 ng/ml. However, the viability of OM-10.1 cells further decreased with
      increasing concentrations of Fas-mAb when exposed simultaneously to TNF-alpha,
      suggesting that TNF-alpha sensitizes the cells to Fas-mAb-induced cell death.
      FACScan analysis and DNA gel electrophoresis revealed that the cell death was due
      to apoptosis. Such an effect of Fas-mAb was not identified in U1 cells. TNF-alpha
      but not Fas-mAb activated latent HIV-1 in OM-10.1 and U1 cells. Although all
      myelomonocytic cell lines expressed Fas on their cell surface, TNF-alpha
      significantly up-regulated the expression of Fas in only OM-10.1 cells. These
      results indicate that, unlike T cells, HIV-1-infected myelomonocytic cells are
      generally resistant to the Fas-mediated apoptosis. However, they would become
      sensitive to the apoptosis if the expression of Fas could be up-regulated by TNF
      alpha or other factors.

PMID- 9255762
TI  - Demonstration of Borna disease virus (BDV) in specific regions of the brain from
      horses positive for serum antibodies to BDV but negative for BDV RNA in the blood
      and internal organs.
AB  - Sero- and molecular-epidemiological studies on Borna disease virus (BDV)
      infection show that BDV RNA is not always detected in the peripheral blood
      mononuclear cells (PBMCs) from serum anti-BDV antibody-positive individuals such
      as horses, sheep, cattle, cats, and humans. In this study we demonstrated BDV RNA
      signals by polymerase chain reaction only in restricted regions of the brain from
      horses with locomotor disease. Four of six horses examined showed apparently
      positive reactions for anti-BDV antibodies. Specific regions of the brain of
      these four horses were positive for BDV RNA but the internal organs, lymph nodes,
      and PBMCs were negative. Histological studies of their brains revealed no
      apparent histological abnormalities such as inflammatory reactions. These results
      suggest that BDV chronically infects certain restricted regions of brain in
      seropositive horses.

PMID- 9255763
TI  - T cell receptor specificities of Toxoplasma gondii-reactive mouse CD4+ T
      lymphocytes and Th1 clones.
AB  - The Toxoplasma gondii-directed CD4+ T cell response in chronically infected mice
      was studied with respect to both T cell receptor diversity and antigen
      specificities. T cell receptor chains V beta 4, 6, 8, 10, and 14 were
      predominantly found on toxoplasma-reactive CD4+ splenocytes. This repertoire was
      also detected among T. gondii-specific CD4+ T cell clones. Analysis of clonotypic
      cytokine profiles revealed typical Th1 clones secreting interleukin-2, interferon
      gamma and tumour necrosis factor activity and Th2 clones producing interleukin-4
      and interleukin-10. Five distinct toxoplasma antigens (p26, p40, p55, p58 and
      p60) were detected in electrophoretically separated toxoplasma lysate by five
      individual Th1 clones. Parallel testing of CD4+ T lymphocytes from infected mice
      confirmed that these specificities constitute the peak immunogenic fractions of
      toxoplasma lysate. The expression patterns of two clonotypic, T cell-stimulatory
      parasite antigens were studied in detail. While p55 was expressed by mouse
      virulent and avirulent T. gondii isolates and in both the tachyzoite and
      bradyzoite stages, p58 was detected only in virulent strains from intraspecies
      subgroup I. Thus, we describe the heterogeneity of toxoplasmic immunodominant T
      cell antigens including a 58-kDa group I-restricted molecule which may provide a
      marker for virulent isolates.

PMID- 9255764
TI  - The efficacy and safety of Skinner herpes simplex vaccine towards modulation of
      herpes genitalis; report of a prospective double-blind placebo-controlled trial.
AB  - A randomised, placebo-controlled, multi-centre trial of intracellular subunit
      herpes simplex virus (HSV) type 1 vaccine NFU.Ac.HSV-1(S-)MRC (Skinner vaccine)
      was conducted at three medical centres in the United States. Subjects with
      documented herpes genitalis of at least 1-year duration and a history of six or
      more genital HSV recurrences in the 12 months prior to study entry were
      randomised to receive vaccine or placebo at 0, 1 and 2 months. Vaccination
      induced significant neutralising, enzyme-linked immunosorbent assay and
      lymphocyte transformation response to HSV-1 antigen. The frequency of recurrences
      was reduced in the vaccinated female patients at both 3 and 6 months following
      vaccination with an overall reduction in patients of both sexes which did not
      reach statistical significance. Recurrence severity was reduced as measured by
      decreased number of lesions and associated symptoms per recurrence (P = 0.04).
      The data suggest that clinical manifestations of latent HSV genital infection may
      be modified by therapeutic immunisation.

PMID- 9255765
TI  - The hemagglutinin of Staphylococcus saprophyticus binds to a protein receptor on
      sheep erythrocytes.
AB  - Staphylococcus saprophyticus, an important cause of urinary tract infections,
      produces two major surface proteins, the S. saprophyticus surface-associated
      protein (Ssp) and the hemagglutinin, which mediates fibronectin binding and also
      functions as the major adhesion of the organism. The hemagglutinating and
      fibronectin binding functions probably reside on different parts of the molecule.
      To identify a receptor on eukaryotic cells, binding and inhibition studies with
      acidic and neutral glycosphingolipids, carbohydrates, and proteins of sheep
      erythrocyte membranes were conducted. S. saprophyticus did not bind to any
      glycosphingolipid and no inhibition was observed when hemagglutination assays
      were done in the presence of carbohydrates or fibronectin. Neither treatment of
      erythrocytes with galactose oxidase or neuraminidase and galactose oxidase nor
      mild periodate oxidation of erythrocytes reduced hemagglutination. However,
      proteinase-treated erythrocytes were no longer agglutinated. Similarly, untreated
      erythrocyte membranes inhibited hemagglutination, whereas proteinase-treated
      membranes did not. In addition, only hemagglutinating strains bound to 60- and 21
      kDa sheep erythrocyte membrane proteins on ligand blots, and these proteins
      inhibited hemagglutination. Our data indicate that, in contrast to many other
      hemagglutinins, the receptor on sheep erythrocytes for S. saprophyticus is a
      protein.

PMID- 9255766
TI  - Immunoprophylactic properties of 71-kDa cell wall-associated protein antigen of
      Mycobacterium tuberculosis H37Ra.
AB  - Proteins associated with the cell wall peptidoglycan (CW-Pr) of Mycobacterium
      tuberculosis H37Ra were isolated to evaluate their immunoreactivity and
      immunoprophylactic properties against experimental tuberculosis. Chemical
      treatment of the cell wall with trifluoromethanesulfonic acid: anisole (2:1)
      resulted in the release of three proteins of 71, 60 and 45 kDa as resolved by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A comparative study of
      immune responses elicited to individual proteins in mice immunized with CW-Pr
      emulsified in incomplete Freund's adjuvant showed the 71-kDa protein to be the
      most immunoreactive antigen. This 71-kDa protein was found to cross-react with
      the 70-kDa heat shock protein from M. leprae and possessed ATPase activity. Mice
      immunized with the 71-kDa protein exhibited significantly higher immune
      responses, on the basis of T and B cell reactivity, as compared to a M. bovis
      Bacillus Calmette Guerin (BCG)-vaccinated group. The culture supernatants
      collected from 71-kDa stimulated lymphocytes stimulated exhibited increased
      interferon-gamma and interleukin-2 production. The protective efficacy of the 71
      kDa protein in comparison to BCG was determined by challenging the mice with a
      virulent strain M. tuberculosis H37Rv. The 71-kDa protein was found to be more
      protective in animals challenged at 8 and 16 weeks post immunization, shown by
      increased survival rates and decreased viable bacilli counts in the target organs
      as compared to BCG-vaccinated animals.

PMID- 9255767
TI  - Pore-forming properties of proteolytically nicked staphylococcal alpha-toxin: the
      ion channel in planar lipid bilayer membranes.
AB  - Staphylococcal alpha-toxin is a single-chain protein with a molecular mass of
      33.2 kDa, which can form large water-filled pores both in lipid bilayers and in
      erythrocyte membranes. Limited proteolysis of the purified toxin with proteinase
      K led to time-dependent changes of all the functional features of the channels
      formed by the toxin. Single-channel conductance in planar bilayers was decreased
      about threefold. The anion selectivity of the channel was replaced with cation
      selectivity and the asymmetry in the current-voltage relationship of the channel
      became more pronounced. At the same time the nicked toxin kept its full ability
      to form ion channels in lipid bilayers, although it lost a considerable part of
      its hemolytic activity. In planar bilayers and in erythrocyte membranes, the
      proteolytically nicked toxin actually formed channels with a slightly smaller
      diameter (approximately 1.2 times) than that formed by the native toxin. This
      decrease was not marked enough to explain changes in the biological effects of
      the nicked toxin. The change in channel selectivity induced by the cleavage is
      considered to be the major determinant of the changes in the biological effects
      of the nicked toxin.

PMID- 9255769
TI  - HGS-TIGR splits, opportunity knocks.

PMID- 9255768
TI  - The lppC gene of Streptococcus equisimilis encodes a lipoprotein that is
      homologous to the e (P4) outer membrane protein from Haemophilus influenzae.
AB  - We report the cloning, sequencing, and analysis of a novel chromosomal gene of
      Streptococcus equisimilis strain H46A that codes for a membrane lipoprotein,
      designated LppC. The lppC gene is located 3' adjacent to, and co-oriented with,
      the unrelated gapC gene that encodes the previously characterized glyceraldehyde
      3-phosphate dehydrogenase. Sequencing of lppC revealed an 855-bp open reading
      frame that predicted a 32.4-kDa polypeptide possessing a potential lipoprotein
      signal sequence and modification site (VTGC). Signal sequence processing of LppC
      synthesized in the homologous host or expressed from plasmid pLPP2 in Escherichia
      coli was sensitive to globomycin, a selective inhibitor of lipoprotein-specific
      signal peptidase II. Subcellular localization of LppC using polyclonal antibodies
      raised to the hexahistidyl-tagged protein proved LppC to be tightly associated
      with the cytoplasmic membrane of S. equisimilis and with the outer membrane of E.
      coli JM109 (pLPP2). Southern, Northern and Western analyses indicated that lpp
      was conserved in S. pyogenes, and transcribed independently of gap as
      monocistronic 0.9-kb mRNA from a sigma 70-like consensus promoter. Database
      searches found homology of LppC to the hel gene-encoded outer membrane protein e
      (P4) from Haemophilus influenzae to which it exhibits 58% sequence similarity.
      However, unlike the hel gene, lppC was unable to complement hemA mutants of E.
      coli for growth on hemin as sole porphyrin source in aerobic conditions.
      Furthermore, neither the wild type nor an lppC insertion mutant of S. equisimilis
      could grow on hemin in iron-limited medium. These results, together with findings
      indicating that S. equisimilis H46A had no absolute requirement for iron, led us
      to conclude that lppC, in contrast to hel, is not involved in hemin utilization
      and has yet to be assigned a function.

PMID- 9255770
TI  - EuropaBio's regulatory niche.

PMID- 9255771
TI  - The biosafety protocol slouches toward Montreal.

PMID- 9255772
TI  - Agriculture is biotechnology's future in Europe.

PMID- 9255773
TI  - Paradigms and the rise (or fall?) of molecular biology.

PMID- 9255774
TI  - Upgrading German genomics.

PMID- 9255776
TI  - ICH-4 sets course for global harmony.

PMID- 9255775
TI  - Chemokine inhibitors for HIV.

PMID- 9255777
TI  - Short-order Sindbis vector targeting.

PMID- 9255779
TI  - SCID mouse models: more than furry flasks.

PMID- 9255778
TI  - Dusting off recombinant allergens.

PMID- 9255780
TI  - scFvs get down to basics: how MuSK makes synapses.

PMID- 9255781
TI  - Stress is good and bad for tumors.

PMID- 9255782
TI  - India: 50 years after independence.

PMID- 9255783
TI  - Australia: ready for business.

PMID- 9255784
TI  - Biotechnology in the Islamic world.

PMID- 9255785
TI  - Minnesota's biotechnology portfolio.

PMID- 9255786
TI  - Markl opens Max-Planck's doors.

PMID- 9255787
TI  - Biotechnology in Mexico: planning for the future.

PMID- 9255788
TI  - Natural antisense RNA/target RNA interactions: possible models for antisense
      oligonucleotide drug design.
AB  - Current antisense oligonucleotides designed for drug therapy rely on Watson-Crick
      base pairing for the specificity of interactions between antisense and target
      molecules. However, thermodynamically stable duplexes containing non-Watson-Crick
      pairs have been formed with synthetic oligonucleotides. There are also numerous
      examples of non-canonical base pairs that participate in stable intra- and inter
      molecular RNA/RNA pairing in prokaryotic and eukaryotic cells. Several natural
      antisense RNA/target RNA duplexes contain looped-out and bulged positions as well
      as non-canonical pairs as exemplified by formation of the Escherichia coli
      antisense micF RNA/ompF mRNA duplex. Secondary structures and the phylogenetic
      conservation of nucleotide sequences are well characterized in this system.
      Natural antisense/ target interactions may serve as models for determining
      possible and optimal antisense/target interactions in oligonucleotide drug
      design.

PMID- 9255789
TI  - Engineering of the major house dust mite allergen Der f 2 for allergen-specific
      immunotherapy.
AB  - A major problem with allergen-specific immunotherapy involving repeated injection
      of allergens is the risk of an anaphylactic reaction. We engineered the major
      house dust mite allergen, Der f 2, to reduce its capacity to induce skin test
      reactivity and histamine release from peripheral blood basophils in allergic
      patients. The engineered allergen, in which the disulfide bond that linked the N-
      and C-terminal sequences of Der f 2 was disrupted, retained T-cell epitopes
      essential for immunotherapy and ability to stimulate T-cell proliferation. Such
      engineered allergens are potentially useful for safer and more effective
      immunotherapy for allergies.

PMID- 9255790
TI  - Blockade of CD2-LFA-3 interactions protects human skin allografts in
      immunodeficient mouse/human chimeras.
AB  - A human skin allograft injury model in immunodeficient mice, engrafted with human
      peripheral blood mononuclear cells from a different donor, has been used to test
      whether reagents that block human T cell CD2 interactions with its principal
      ligand, LFA-3 (CD58), can inhibit immune reactions in vivo. In this model, human
      skin grafts show a reproducible pattern of progressive human T-cell infiltration
      and human graft microvascular injury that resembles human first-set skin graft
      rejection. Murine Mab to human LFA-3 or human LFA-3-IgG1 fusion protein, but not
      isotype-matched control antibodies, each markedly protected skin grafts from
      leukocyte infiltration and injury. These data provide the first evidence that LFA
      3 functions in vivo and establish the ability of this new model to test human
      specific immune modulators.

PMID- 9255791
TI  - Cell-specific targeting of Sindbis virus vectors displaying IgG-binding domains
      of protein A.
AB  - Sindbis virus can infect a broad range of insect and vertebrate cell types due to
      the widespread distribution of the cellular receptor for the virus. The
      development of Sindbis virus vectors that target specific cell types could have
      important implications for the design of gene therapy strategies. To achieve this
      goal we have designed and constructed Sindbis virus particles displaying the IgG
      binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector
      has minimal infectivities against baby hamster kidney and human cell lines. When
      used in conjunction with monoclonal antibodies that react with cell-surface
      antigens, however, the protein A-envelope chimeric virus was able to infect human
      cell lines with high efficiency. Infection rates were 90% or higher for human
      lymphoblastoid cells. A variety of cells could be targeted by changing the
      monoclonal antibody without generating a new recombinant virus.

PMID- 9255792
TI  - Direct demonstration of MuSK involvement in acetylcholine receptor clustering
      through identification of agonist ScFv.
AB  - MuSK is a tyrosine kinase localized to the postsynaptic surface of the
      neuromuscular junction. We have searched for modulators of MuSK function using a
      library of human single chain variable region antibodies (scFv) that can be
      displayed on M13 phage or expressed as soluble protein. A panel of 21 independent
      MuSK-specific scFv, identified in a screen for binding to MuSK-Fc immunoadhesin,
      were examined for ability to induce proliferation in a factor dependent cell line
      (Ba/F3) through a chimeric receptor, MuSK-Mpl. Four of the scFv induced a
      proliferative response, suggesting an ability to induce dimerization of MuSK.
      These scFv were also able to induce tyrosine phosphorylation of full-length MuSK
      and retained this ability when re-engineered to be expressed as authentic (and
      dimeric) human IgG molecules. Addition of agonist scFv to a cultured myotube cell
      line induced AChR clustering and tyrosine phosphorylation. These results provide
      direct evidence that MuSK activation is capable of triggering a key event in
      neuromuscular junction formation and further demonstrate that large libraries of
      phage-displayed scFv provide a robust method for generating highly specific
      agonist agents.

PMID- 9255793
TI  - Binding proteins selected from combinatorial libraries of an alpha-helical
      bacterial receptor domain.
AB  - Small protein domains, capable of specific binding to different target proteins
      have been selected using combinatorial approaches. These binding proteins, called
      affibodies, were designed by randomization of 13 solvent-accessible surface
      residues of a stable alpha-helical bacterial receptor domain Z, derived from
      staphylococcal protein A. Repertoires of mutant Z domain genes were assembled and
      inserted into a phagemid vector adapted for monovalent phage display. Two
      libraries, each comprising approximately 4 x 10(7) transformants, were
      constructed using either an NN(G/T) or an alternative (C/A/G)NN degeneracy.
      Biopanning against the target proteins Taq DNA polymerase, human insulin, and a
      human apolipoprotein A-1 variant, showed that in all cases significant
      enrichments were obtained by the selection procedures. Selected clones were
      subsequently expressed in Escherichia coli and analyzed by SDS-PAGE, circular
      dichroism spectroscopy, and binding studies to their respective targets by
      biospecific interaction analysis. The affibodies have a secondary structure
      similar to the native Z domain and have micromolar dissociation constants (KD)
      for their respective targets.

PMID- 9255794
TI  - Solid stress inhibits the growth of multicellular tumor spheroids.
AB  - In normal tissues, the processes of growth, remodeling, and morphogenesis are
      tightly regulated by the stress field; conversely, stress may be generated by
      these processes. We demonstrate that solid stress inhibits tumor growth in vitro,
      regardless of host species, tissue of origin, or differentiation state. The
      inhibiting stress for multicellular tumor spheroid growth in agarose matrices was
      45 to 120 mm Hg. This stress, which greatly exceeds blood pressure in tumor
      vessels, is sufficient to induce the collapse of vascular or lymphatic vessels in
      tumors in vivo and can explain impaired blood flow, poor lymphatic drainage, and
      suboptimal drug delivery previously reported in solid tumors. The stress-induced
      growth inhibition of plateau-phase spheroids was accompanied, at the cellular
      level, by decreased apoptosis with no significant changes in proliferation. A
      concomitant increase in the cellular packing density was observed, which may
      prevent cells from undergoing apoptosis via a cell-volume or cell-shape
      transduction mechanism. These results suggest that solid stress controls tumor
      growth at both the macroscopic and cellular levels, and thus influences tumor
      progression and delivery of therapeutic agents.

PMID- 9255795
TI  - Drug metabolism by Escherichia coli expressing human cytochromes P450.
AB  - The broad substrate specificity of the cytochrome P450 (P450) enzyme superfamily
      of heme-thiolate proteins lends itself to diverse environmental and
      pharmaceutical applications. Until recently, the primary drawback in using living
      bacteria to catalyze mammalian P450-mediated reactions has been the paucity of
      electron transport from NADPH to P450 via endogenous flavoproteins. We report the
      functional expression in Escherichia coli of bicistronic constructs consisting of
      a human microsomal P450 enzyme encoded by the first cistron and the auxiliary
      protein NADPH-P450 reductase by the second. Expression levels of P450s ranged
      from 35 nmol per liter culture to 350 nmol per liter culture, with expression of
      NADPH-P450 reductase typically ranging from 50% to 100% of that of P450.
      Transformed bacteria metabolized a number of typical P450 substrates at levels
      comparable to isolated bacterial membranes fortified with an NADPH-generating
      system. These rates compare favorably with those obtained using human liver
      microsomes as well as those of reconstituted in vitro systems composed of
      purified proteins, lipids, and cofactors.

PMID- 9255796
TI  - Biocatalytic plastics as active and stable materials for biotransformations.
AB  - Enzyme-containing polymeric materials have been developed that have high activity
      and stability in both aqueous and organic media. These biocatalytic plastics,
      containing alpha-chymotrypsin and subtilisin Carlsberg, can contain up to 50%
      (w/w) total protein in plastic materials such as poly(methyl methacrylate,
      styrene, vinyl acetate, and ethyl vinyl ether). The activation achieved in
      organic solvents by incorporating proteases in plastic matrices allows for the
      efficient synthesis of peptides, and sugar and nucleoside esters. The marriage of
      enzyme technology with polymer chemistry opens up an array of unique applications
      for plastic enzymes, including active and stable biocatalysts in paints,
      coatings, resins, foams, and beads, as well as membranes, fibers, and tubings.

PMID- 9255797
TI  - Increased potato tuber size resulting from apoplastic expression of a yeast
      invertase.
AB  - The role of sucrose cleavage in determining sink strength in potato was
      investigated by generating transgenic potato plants that expressed a yeast
      invertase in either the cytosol or apoplast of tubers. Cytosolic localization
      gave rise to a reduction in tuber size and an increase in tuber number per plant
      whereas apoplastic targeting led to an increase in tuber size and a decrease in
      tuber number per plant. Sink organ size can be manipulated through modification
      of sucrose metabolism.

PMID- 9255798
TI  - Laboratory record keeping.

PMID- 9255799
TI  - Base excision sequence scanning.

PMID- 9255800
TI  - Isolation of genomic DNA from plant tissues.

PMID- 9255801
TI  - Tetanus toxoid purification: a case study.

PMID- 9255802
TI  - Biotechnology valuation.

PMID- 9255803
TI  - [Jejunal pouch and interposition reconstruction after a total gastrectomy for
      cancer].
AB  - The authors modified the operative procedures used in pouch and interposition
      (PI) reconstruction in an attempt to improve the surgical results after a total
      gastrectomy, because a randomized controlled trial had revealed that the clinical
      assessment of PI was quite poor, even though it is a physiological route. In most
      of the treated patients, the gastric emptying test revealed delayed emptying, and
      an X-ray video film showed folding and twisting of the jejunal conduit between
      the pouch and duodenum, which disturbed the transmission of the nutrition.
      Modified PI (m-PI) was performed by decreasing the length of the jejunal conduit
      and widening the jejunal pedicle to preserve the blood and nerve supply. The m-PI
      group showed a lower incidence of symptoms, a greater food intake, and a greater
      weight recovery than the PI group. The gastric emptying test also revealed an
      acceptable degree of emptying. We conclude that the m-PI reconstruction is more
      useful for improving the postoperative quality of life than the previously used
      method of PI reconstruction.

PMID- 9255804
TI  - [Jejunal pouch interposition after total gastrectomy].
AB  - The results and procedures of interposed jejunal pouch after total gastrectomy
      for gastric cancer are reported. Basic requirements of reconstruction after total
      gastrectomy are 1) formation of a food reservoir, 2) maintenance of duodenal
      continuity, 3) avoidance of reflux esophagitis, 4) gradual emptying of reservoir
      into the small intestine. Since 1950's, several procedures of gastric substitutes
      have been reported. But they were not widely performed. Because scientific
      evaluation of the value of gastric substitutes was difficult and the operative
      procedures were time consuming and complicated. With an increasing ratio of early
      gastric cancer in 1990's, the importance of post-operative QOL, such as food
      intake and body weight maintenance, in patients after total gastrectomy has been
      recognized. Our procedure is a double lumen jejunal pouch distal to a interposed
      jejunum. The length of interposed jejunum is 20 cm and that of pouch is 10 cm.
      Using surgical staplers, this procedure is safe and simple. Jejunal pouch
      interposition leads to a satisfactory symptomatic and nutritional result in
      gastrectomized patients.

PMID- 9255805
TI  - [Pedicle transplantation of a transverse colon segment after total gastrectomy].
AB  - This report is concerned with series of patients with advanced gastric cancer in
      whom transverse colon segment interposition, namely an end-to-end
      esophagocolostomy plus coloduodenostomy (Type-I) from 1965 to 1970 and an end-to
      side esophagocolostomy plus coloduodenostomy (Type-II) from 1986 to 1996 were
      performed after total gastrectomy. Fifty-two patients with Type-I reconstruction
      and 133 patients with Type-II reconstruction after total gastrectomy were
      studied. Postoperative nutritional condition and complications were investigated
      and changes in the size and high amplitude propagated contractions of the
      interposed colon were measured. RESULTS AND CONCLUSION: The interposed transverse
      colon segment which was placed in an iso-peristaltic fashion between esophagus
      and duodenum dilated gradually and capable of taking a reasonable quantity of
      food at one time. The nutritional status was good especially in long-term
      survivors. Complications such as reflux esophagitis (12.0% after Type-I and zero%
      in Type-II fashion) have occurred. The iodinated Triolein 131I absorption test
      has shown 92.4% absorption rate of the material, a value comparable to that of
      patients subjected to Billroth-I type gastric resection. In conclusion, pedicle
      transplantation of a segment of the transverse colon, especially Type-II fashion,
      is feasible and useful to use in patients undergoing total gastrectomy.

PMID- 9255806
TI  - [Evaluation of ileocolon interposition after total gastrectomy].
AB  - The most serious complaints after total gastrectomy are alkaline esophagitis and
      postalimentary syndrome. We have performed ileocolon interposition as a gastric
      substitution which uses the ileocecal valve to prevent bile reflux. The ileocolon
      segment consists of 7 cm of terminal ileum and 10 cm of coecum and ascending
      colon on a vascular pedicle. This isolated segment is rotated upwards between the
      esophagus and the duodenum. To evaluate the function of the ileocolon as a
      gastric substitute, Barium X rays, O-GTT and gastric emptying time (99Tc EDTA)
      were examined. Barium X-rays showed that the air at the coecal portion looks like
      a gastric fornix and there is no barium reflux into the esophagus even in the
      supine position. Likewise, there were no complaints from patients of symptoms of
      reflux esophagitis. In case of Rouxen-Y reconstructions, blood sugar level after
      O-GTT show oxyhyperglycemia. Those in ileocolon interposition rose rapidly, but
      almost to the same degree as in normal subjects. The appearance of the gastric
      emptying curve using Tc-DTPA in case of ileocolon interposition shows that there
      is good reservoir function.

PMID- 9255807
TI  - [A new reconstructive procedure, interposition of a jejunal pouch after proximal
      gastrectomy].
AB  - In this chapter we mention the significance or advantage of the new
      reconstructive procedure, interposition of a jejunal pouch after proximal
      gastrectomy. Instead of oesophagogastrostomy which often brought many
      postoperative complications, various techniques of anastomosis such as
      conventional jejunal interposition or double tract method were contrived.
      Although these techniques could reduce the incidence of postoperative problems
      such as reflux oesophagitis, it is very difficult to examine or remedy beyond the
      oesophagojejunostomy site after surgery. On the other hand, interposition of a
      jejunal pouch showed us many advantages. The volume of reconstructed stomach was
      adequate and the patients could eat enough actually. In case of need, endoscopic
      fiber could enter the remnant stomach or duodenum very easily. This is the big
      advantage for the treatment of the upper GI and hepato-biliary pancreatic
      diseases endoscopically or radiologically after proximal gastrectomy. For these
      reasons, we usually use interposition of a jejunal pouch between the oesophagus
      and remnant stomach after proximal gastrectomy.

PMID- 9255808
TI  - [Jejunal pouch interposition and distal gastrectomy].
AB  - We developed a new technique of reconstruction in Billroth 1 gastrectomy, jejunal
      pouch interposition (JPI). The interposed jejunal segment consists of a
      proximally double-plicated pouch and a distally isoperistaltic conduit. From 1987
      to 1994, the JPI was performed on 102 patients with gastric carcinoma. The
      postoperative functional assay was carried out at least one year later after
      surgery. Sixty-five patients with the conventional Billroth 1 reconstruction (B
      1) during the same period were employed as the control. Gastric emptying time
      estimated with scinti-scanning was significantly delayed in the JPI group
      compared with the B-1 group (p < 0.05). All individuals with JPI had meals three
      times a day whereas 13% of those with B-1 required those more than three times (p
      < 0.05). The incidence of dumping syndrome was significantly lower in the JPI
      group (6%) than the B-1 group (20%) (p < 0.05). The reflux of bile into the
      residual stomach was observed in the scintiscanning at 78% of patients with B-1
      whereas 10% of those with JPI (p < 0.01). Endoscopy revealed that regurgitation
      gastritis was significantly decreased in the JPI group compared with that in the
      B-1 group (p < 0.01). These results suggest that the JPI prevents small stomach
      syndrome, dumping syndrome and alkaline reflux gastritis after the B-1
      reconstruction.

PMID- 9255809
TI  - [A device in reconstruction method after distal subtotal gastrectomy: special
      reference to double tract method with jejunal pouch].
AB  - In the surgery of gastric cancer, it is necessary to consider not only the
      curability of gastric resection but also the quality of life of the patients in
      the choice of reconstruction method after distal gastrectomy. We have devised the
      jejunal pouch double tract method after gastrectomy. We reported in this study on
      the details of method and the satisfactory results. We employed 15 cases of
      gastric cancer which should be resected over three quarters of the stomach
      because the tumor occupation were in the middle third of the stomach and were
      expected long survival period. The operative procedure was as follows: (1)
      completion of gastric resection and lymph node dissection, (2) separation of
      jejunum at the site of 25 cm anal side from the Treitz's ligament, (3) pulling up
      the anal side of the jejunum preparing double jejunal pouch with approximately 10
      cm in length using GIA, (4) anastomosis between residual stomach and jejunal
      pouch, (5) duodenojejunostomy at the site of 3-5 cm anal side from the pouch, (6)
      jejunojejunostomy at the site of 15 cm anal side from the duodenojejunostomy.
      Double tract reconstruction with jejunal pouch after distal gastrectomy is well
      balanced method in the storage and discharging capacity, and useful in the view
      of better quality of life, especially in the cases which could be expected long
      survival period.

PMID- 9255810
TI  - [A case of empyema with a bronchopleural fistula treated by a pedicle muscle flap
      with the thick parietal pleura].
AB  - A 65-year-old male with a bronchopleural fistula of 10 mm in diameter underwent
      thoracoplasty combined with a pedicle muscle flap following open thoracic window.
      He had been treated by gastrectomy and right upper lobectomy because of gastric
      perforation and lung tuberculosis before empyema. Sterilization for the empyema
      cavity through the thoracic window was done for 255 days, obliteration of the
      empyema cavity was achieved by a muscle flap with the thick parietal pleura. The
      parietal pleura which was not separated from the intercostal pleura which was not
      separated from the intercostal muscle was used for reinforcement of the muscle
      flap against the high intra-tracheal pressure. There was no postoperative relapse
      of empyema for 9 months.

PMID- 9255811
TI  - [A case of anastomotic aneurysm-enteric fistula].
AB  - We successfully performed circulation reconstructive surgery and repair of a
      small intestine resection, primarily at an anatomical position, for perforation
      of a pseudoaneurysm in the small intestine, which occurred in an anastomosis site
      of the right leg of a Y graft of an artificial blood vessel and internal iliac
      artery graft on a patient, at the remote time of 18 years after she had received
      a Y-type artificial blood vessel. The patient's life was saved. The results
      suggest that it is important to make a definitive diagnosis quickly after the
      occurrence of symptoms and to select an appropriate surgical technique according
      to the findings of infection adjacent to the perforation site.

PMID- 9255812
TI  - A perspective from Mopane.

PMID- 9255813
TI  - Dioptric power: its nature and its representation in three- and four-dimensional
      space.
AB  - Dioptric power expressed in the familiar three-component form of sphere,
      cylinder, and axis is unsuited to mathematical and statistical treatments; there
      is a particular class of power that cannot be represented in the familiar form;
      and it is possible that sphere, cylinder, and axis will prove inadequate in
      future clinical and research applications in optometry and ophthalmology.
      Dioptric power expressed as the four-component dioptric power matrix, however,
      overcomes these shortcomings. The intention in this paper is to provide a
      definitive statement on the nature, function, and mathematical representation of
      dioptric power in terms of the matrix and within the limitations of paraxial or
      linear optics. The approach is universal in the sense that its point of departure
      is not power of the familiar form (that is, of thin systems) but of systems in
      general (thick or thin). Familiar types of power are then seen within the context
      of power in general. Dioptric power is defined, for systems that may be thick and
      astigmatic, in terms of the ray transfer matrix. A functional definition is
      presented for dioptric power and its components: it defines the additive
      contribution of incident position to emergent direction of a ray passing through
      the system. For systems that are thin (or thin-equivalent) it becomes possible to
      describe an alternative and more familiar function; for such systems dioptric
      power can be regarded as the increase in reduced surface curvature of a wavefront
      brought about by the system as the wavefront passes through it. The curvital and
      torsional components of the power are explored in some detail. Dioptric power, at
      its most general, defines a four-dimensional inner product space called dioptric
      power space. The familiar types of power define a three-dimensional subspace
      called symmetric dioptric power space. For completeness a one-dimensional
      antisymmetric power space is also defined: it is orthogonal in four dimensions to
      symmetric dioptric power space. Various bases are defined for the spaces as are
      coordinate vectors with respect to them. Vectorial representations of power in
      the literature apply only to thin systems and are not obviously generalizable to
      systems in general. They are shown to be merely different coordinate
      representations of the same subspace, the space of symmetric powers. Some of the
      uses and disadvantages of the different representations are described. None of
      the coordinate vectors fully represent, by themselves, the essential character of
      dioptric power. Their use is limited to applications, such as finding a mean,
      where addition and scalar multiplication are involved. The full character of
      power is represented by the dioptric power matrix; it is in this form that power
      is appropriate for all mathematical relationships.

PMID- 9255814
TI  - Power vectors: an application of Fourier analysis to the description and
      statistical analysis of refractive error.
AB  - The description of sphero-cylinder lenses is approached from the viewpoint of
      Fourier analysis of the power profile. It is shown that the familiar sine-squared
      law leads naturally to a Fourier series representation with exactly three Fourier
      coefficients, representing the natural parameters of a thin lens. The constant
      term corresponds to the mean spherical equivalent (MSE) power, whereas the
      amplitude and phase of the harmonic correspond to the power and axis of a Jackson
      cross-cylinder (JCC) lens, respectively. Expressing the Fourier series in
      rectangular form leads to the representation of an arbitrary sphero-cylinder lens
      as the sum of a spherical lens and two cross-cylinders, one at axis 0 degree and
      the other at axis 45 degrees. The power of these three component lenses may be
      interpreted as (x,y,z) coordinates of a vector representation of the power
      profile. Advantages of this power vector representation of a sphero-cylinder lens
      for numerical and graphical analysis of optometric data are described for
      problems involving lens combinations, comparison of different lenses, and the
      statistical distribution of refractive errors.

PMID- 9255815
TI  - Clinical refraction in three-dimensional dioptric space revisited.
AB  - The traditional clinical designation of spherocylindrical power unambiguously
      specifies the refractive properties of a thin lens or refractive surface. This
      representation of dioptric power is not, however, optimum in mathematical terms,
      as is apparent when, for example, two spherocylindrical lens powers are added.
      Alternative systems have been described which are not subject to this same type
      of difficulty, and the essential feature of these other systems is that
      spherocylindrical power is defined in terms of a three-dimensional dioptric space
      in which the axes are usually orthogonal. The advantages of this orthogonality
      can be exploited in the practice of clinical refraction, provided lens powers in
      these three dimensions can be physically implemented. Systems using these
      characteristics have been introduced in the past, but the clinical community has
      not adopted them on a widespread basis. However, systems which take advantages of
      these features do have unique advantages relative to traditional clinical
      refraction procedures. These characteristics, and refractive procedures which
      exploit their advantages, are described.

PMID- 9255816
TI  - The refractive group.
AB  - Spherocylindrical optical elements can be decomposed into a sphere-equivalent
      component and two cross-cylinder components, oriented at 45 degrees to one
      another. These components in turn can be represented with a simple matrix
      formalism. This matrix formalism allows it to be seen that the components also
      form members of an eight element group, designated the refractive group. The
      structure of this group is developed including its algebra and its representation
      with Cayley diagrams. The group is identified as the eight element dihedral
      group, D4, and is compared to another well-known eight element group, the
      quaternion group. An example is given using the group formal algebra to develop
      the transfer equations for spherocylindrical wavefronts. Certain properties of
      propagating spherocylindrical wavefronts, such as nonrotation of cylinder axes,
      are seen to come directly as consequences of the group properties.

PMID- 9255817
TI  - Equivalent dioptric power asymmetry relations for thick astigmatic systems.
AB  - For optical systems consisting of separated obliquely crossed toric interfaces,
      the equivalent dioptric power has principal meridians that are not necessarily
      orthogonal to each other. In this case it takes four parameters to specify the
      equivalent power. A set of parameters convenient for ophthalmic optics consists
      of three traditional spherocylindrical parameters SC x theta together with a
      dioptric asymmetry parameter g. The parameter g has been described as "so far"
      being entirely mathematical in nature. The purpose of this paper is to develop
      further optical knowledge about the equivalent power asymmetry g. The method was
      a theoretical and numerical study involving optics and the dioptric power matrix
      theory. Among the results of this study are a number of new equations involving g
      that clarify the relationships between the nonorthogonal principal meridians and
      the power and axis meridians of SC x theta, as well as explicitly illustrating
      the parameters that can increase or decrease g. It is also pointed out that the
      asymmetry g is formally identical to the circular astigmatism that has previously
      been presented in discussions of ray vector deflection fields (and is used in the
      Humphrey Lens Analyzer measurements). In conclusions, the theoretical relations
      presented here provide optical insight into the equivalent dioptric power
      asymmetry and the parameter g. The relations and insight can assist further
      developments.

PMID- 9255818
TI  - Asymmetric dioptric power matrices and corresponding thick lenses.
AB  - BACKGROUND: When thickness or separation is taken into account, the dioptric
      power of systems with obliquely crossed toric surfaces (OCTS), including some
      corrected and uncorrected human eyes, can be represented by a four-dimensional
      vector space, provided that an arbitrary 2 x 2 asymmetric matrix is the
      equivalent power matrix of some optical system. The provision is crucial for the
      statistical validity of dioptric power matrix methods that take account of
      thickness. Previous efforts to verify the provision have not been satisfactory.
      PURPOSE: To verify the provision. METHODS: Prove that an arbitrary 2 x 2
      asymmetric matrix is the equivalent power for a thick bitoric lens with obliquely
      crossed surface. RESULTS: The procedure and new equations needed to find the
      lens. CONCLUSIONS: The provision holds, which is an important foundation block
      for the validity of the statistical matrix methods for thick astigmatic systems.
      The resulting equations also have optical uses other than statistics.

PMID- 9255819
TI  - Meridional profiles of variance-covariance of symmetric dioptric power: classes
      of variation that are uniform across the meridians of the eye.
AB  - Conventional dioptric power, including refractive status and keratometric
      measurements, can vary in a large variety of ways. The three-dimensional
      character of this type of power implies that six numbers are required for the
      complete representation of its variance: three variances and three covariances.
      Curves (called profiles) that show how these numbers compare in different
      meridians (or transverse directions) of the eye provide a useful graphical
      picture of the variation and its nature. This paper explores an important
      subclass of types of variation in which the variation is the same for all
      meridians. In this subclass the variation of power is said to be uniform across
      all meridians of the eye. It turns out that the uniformity may be either complete
      or partial. In the former case all aspects of the variation are the same. In the
      latter case certain aspects of the variation are the same across all meridians
      whereas others are not; in particular the variance of the torsional component of
      power is the same for every meridian whereas the variance of the curvital
      component changes from meridian to meridian. There is a range of types of
      completely uniform variation from spherical variation at one extreme to
      Jacksonian variation at the other. All types of uniform variation (partial or
      complete) are characterized by two indices called the jacksonian index and the
      completeness index. The types can be represented geometrically as points on the
      triangle of uniformity. Samples of measurements of dioptric power are selected to
      illustrate various types of uniform variation. Methods are presented for
      detecting and classifying uniform variation from profiles of variation and also
      from the variance-covariance matrix. Examples are given of uniform variation of
      refractive status and of keratometry of an eye. The variation is analyzed and
      classified. The concepts and methods are proving to be of fundamental importance
      in the study of the nature and underlying causes of fluctuations of refractive
      status and keratometric measurements.

PMID- 9255820
TI  - Variability of the refractive state: meridional profiles and uniform variation.
AB  - Variation of the refractive state as measured with autorefraction is the result
      of many factors which need to be considered if optometry is to develop a more
      complete understanding of the behavior of the visual process. Various methods can
      be applied to develop such an understanding including scatter plots, meridional
      profiles of variance-covariance, and graphs of uniform variation. These methods
      are used, in this paper, to investigate some results for autorefraction from a
      sample of 106 university students studying optometry. Some of the eyes in the
      sample display variation, some or all of whose characteristics are the same in
      all meridians of the eye. Such eyes are said to exhibit refractive variation that
      is partially or completely uniform across the meridians of the eye. Most eyes,
      however, show variation which appears to depart from uniformity. The typical eye
      in the sample appears to exhibit variation that is mainly spherical in character
      and of a small magnitude in keeping with the view that the accommodative system
      mostly is responsible for this variation. Nevertheless, there is an astigmatic
      component to the variation. The mean variance-covariance matrices for the right
      and left eyes are presented.

PMID- 9255822
TI  - Multimeridional refraction: dependence of the measurement accuracy on the number
      of meridians refracted.
AB  - A Monte Carlo simulation of multimeridional refraction measurements was used to
      investigate the dependence of the accuracy of the measurement on the number of
      meridians refracted, N, and on the standard deviation of a measurement in a
      single meridian, sigma. For the description of the measurement errors, the
      residual refraction values were used, i.e., the parameters of the refraction
      remaining after application of the measured correction. The distributions of the
      residual refraction values were found to be independent of the "true" refraction
      values; in addition, by means of a factor square root of N/sigma, reduced
      residual refraction values could be defined which also were independent of N and
      sigma. A vector space proposed by Lakshminarayanan and Varadharajan (based on
      Long's power matrix) was used to represent the joint distribution of the residual
      refraction values in three-dimensional space. It was found to be a three-variate
      Gaussian distribution with zero mean and diagonal covariance matrix. It could
      further be shown that the vector space proposed by Harris is identical to the one
      used, up to a linear transformation. Several criteria, based on the one- and
      three-dimensional distributions and corresponding to different levels of
      accuracy, are discussed resulting in a wide range of answers about the number of
      meridians to be refracted.

PMID- 9255821
TI  - Short-term keratometric variation in the human eye.
AB  - Previous studies of corneal and keratometric variation used statistical methods
      that were not entirely satisfactory. For the first time, proper multivariate
      statistical methods are applied to evaluate short-term keratometric variation in
      human eyes. Keratometric variation is represented graphically by means of stereo
      pair scatter plots, ellipsoidal confidence regions for mean dioptric power, and
      meridional profiles of variation. There is great variability in the keratometric
      variation displayed by different subjects, although most subjects exhibit
      greatest variation in the vertical meridian of the eye on most of the measuring
      occasions. Variance-covariance matrices based on vector h are given. In some
      cases keratometric variation approaches neutral uniform variation. In many of the
      subjects, mean keratometric measurements change from morning to afternoon,
      usually showing an increase in curvature later in the day. Physical activity may
      increase keratometric variation and mean curvature.

PMID- 9255823
TI  - Repeatability and accuracy of automated refraction: a comparison of the Nikon NRK
      8000, the Nidek AR-1000, and subjective refraction.
AB  - This study assessed the repeatability of the Nikon NRK-8000, the Nidek AR-1000,
      and subjective refraction. In addition, the accuracy of the Nikon and the Nidek
      were evaluated in comparison to subjective refraction. Measurements were taken
      with all 3 techniques on 2 separate occasions with a test-retest separation of at
      least 24 h. The right eyes of 30 normal subjects were used. Repeatability and
      accuracy statistics and plots were generated using matrix representations of
      dioptric power. Subjective refraction was the most repeatable method, with the
      coefficient of repeatability (COR) found to be 0.611, 0.224, and 0.490 in the
      vertical, torsional, and horizontal meridians. The autorefractors' COR was found
      to range from 0.712 to 0.826 for the vertical and horizontal meridians, whereas
      the torsional meridian ranged from 0.224 to 0.319.

PMID- 9255824
TI  - Excess of autorefraction over subjective refraction: dependence on age.
AB  - The purpose of this study was to examine the difference between subjective
      refraction and autorefraction for different age groups. We call the difference
      (autorefraction minus subjective refraction) the excess of autorefraction over
      subjective refraction or the autorefractive excess. Five age groups of 50
      subjects each were used. Subjects in group 1 were aged between 1 and 10 years,
      group 2 between 11 and 20 years, group 3 between 21 and 30 years, group 4 between
      31 and 40 years, and group 5 consisted of subjects over 41 years of age.
      Automatic refraction was performed with an Allergan Humphrey model 580
      autorefractor. The data were analyzed using recently developed statistical
      methods for the analyzing of dioptric power. These methods include the use of the
      coordinate vector h as a representation of dioptric power. The results indicate
      that there is a statistically significant mean autorefractive excess and that the
      mean is different for different age groups. The behavior of the left and right
      eyes appears to be essentially the same. In terms of vector h the mean
      autorefractive excess for both the left and the right eyes of group 1 (1 to 10
      years of age) is approximately (-0.25 0.00-0.43)'. It increases by roughly delta
      h = (0.10 0.00 0.10)' per decade. In more conventional terms the nearest
      equivalent sphere of the mean excess for group 1 is approximately -0.34 D for the
      right and for the left eyes. The mean autorefractive excess for group 1 is
      approximately -0.25 -0.18 x 180. The astigmatic component appears to be the same
      for all age groups, whereas the spherical component increases by approximately
      0.1 D per decade. The standard deviations of the autorefractive excesses are
      relatively large for components h1, and h3 of h: they were between approximately
      0.4 and 0.7 D, possibly decreasing slightly with age. The standard deviation of
      h2 remains at 0.2 D or less for all age groups. The greatest variation of
      autorefractive excess appears to be approximately in the spherical direction in
      symmetric dioptric power space and appears to be less for the older age groups
      than the younger age groups.

PMID- 9255825
TI  - Refractive variation under accommodative demand: curvital and scaled torsional
      variances and covariance across the meridians of the eye.
AB  - Autorefractor measurements were taken on the right eye of 10 students with an
      external target at vergences -1.00 and -3.00 D. The refractive errors in the form
      of sphere, cylinder, and axis were converted to vectors h and variance-covariance
      matrices calculated for different reference meridians. Scatter plots are drawn in
      symmetric dioptric power space. The profiles of curvital and scaled torsional
      variances, the scaled torsional fraction, and the scaled torsional-curvital
      correlation are shown using a polar representation. This form of representation
      provides a meridional pattern of variation under accommodative demand. The
      profile for scaled torsional variance is characteristically in the form of a pair
      of rabbit ears. At both target vergences curvital variance is larger than scaled
      torsional variance in all the meridians of the eye: the relative magnitudes are
      quantified by the scaled torsional fraction. An increase in accommodative demand
      generally results in an increase in variance. The rabbit ears usually become
      larger but less well divided. The correlation between curvital and torsional
      powers is usually positive in the first quadrant and negative in the second
      quadrant. Typical, atypical, and mean typical responses are discussed.

PMID- 9255826
TI  - Refraction and keratometry: departures from and transformations toward
      multivariate normality.
AB  - The multivariate distributional properties of refraction and keratometric data
      were investigated across eyes with power represented in the coordinate system
      introduced by Deal and Toop. Normality and departure from normality were assessed
      with the aid of chi 2 and normal probability plots and by the comparison of
      multivariate sample skewness and kurtosis with critical values. Two of the three
      data sets show significant departure from normality in each of the marginal
      distributions and, therefore, the joint distribution too. The keratometric data
      were normally distributed along the line of spherical powers but departed from
      normality in the astigmatic plane. Marginal transformations are used to reduce
      the departure from normality where necessary. The transformation that was found
      to be successful is essentially an example of a Box/Cox transformation involving
      a shift, ci, and an exponent, gamma i, where i = 1,2,3. For two of the data sets,
      the values of the exponent, gamma i, result in a transformation that is similar
      to a modified square root transformation.

PMID- 9255827
TI  - Invariance of ophthalmic properties under spherocylindrical transposition.
AB  - Ophthalmic properties expressed as functions of dioptric power cannot depend on
      the particular spherocylindrical form (positive or negative cylinder) chosen to
      represent the power: they are necessarily invariant under spherocylindrical
      transposition. This condition of invariance places restrictions on the
      mathematical form that valid ophthalmic functions can assume. Tests are presented
      for checking the validity of proposed ophthalmic functions and properties.
      Examples from the literature are examined, including Keating's concept of
      torsional power and Peters' graphs of expected unaided visual acuity vs.
      ametropia. The former satisfies the condition of invariance but the latter are
      shown to violate the condition for ametropias which are close to spherical. The
      analysis shows partly how the graphs need to be refined. Invariance under
      spherocylindrical transposition can assist the researcher in developing new
      concepts and relationships that depend on power expressed in terms of sphere,
      cylinder, and axis.

PMID- 9255828
TI  - Academic psychiatry and managed care.

PMID- 9255829
TI  - Using the Internet for clinical training: a course on network therapy for
      substance abuse.

PMID- 9255830
TI  - Travel distance to outpatient treatment for depression.

PMID- 9255831
TI  - Past is prologue: moving forward from psychiatric training.

PMID- 9255832
TI  - The CD-ROM as a multipurpose clinical and management tool.

PMID- 9255833
TI  - Academic psychiatry and managed care: a case study.
AB  - An academic department of psychiatry in New York City eliminated the need for
      behavioral managed care intermediaries by transforming itself from a fee-for
      service system to a system able to engage in full-risk capitation contracts. The
      first step was to require health maintenance organizations to contract directly
      with the department. The department formed two legal entities, a behavioral
      management services organization for utilization management and a behavioral
      integrated provider association. The authors describe these entities and review
      the first year of operation, presenting data on enrollees, capitation rates, and
      service utilization for the first three contracts. The fundamental differences in
      the treatment model under managed care and under a fee-for-service system are
      highlighted. The authors conclude that by contracting directly with insurers on a
      full-risk capitation basis, departments of psychiatry will be better able to face
      the economic threats posed by the cost constraints inherent in managed care and
      maintain or re-establish their autonomy as care managers as well as high-quality
      care providers.

PMID- 9255834
TI  - Use of health care services by persons with panic symptoms.
AB  - OBJECTIVE: Patients with panic symptoms are heavy users of the health care
      system, although many do not seek care specifically for those symptoms. This
      study documents utilization of various sources of health care of subjects with
      panic symptoms, including those who met criteria for panic disorder and those
      with infrequent panic, distinguishing between use specifically for panic symptoms
      and use for reasons not related to panic. METHODS: This community-based sample,
      predominantly Mexican American and female, included 97 subjects with panic
      symptoms and 97 matched control subjects with no panic symptoms. Data were
      collected on two-month utilization of various sources of health care both within
      and outside the mainstream health care system, barriers to access to care, and
      levels of medical insurance coverage. RESULTS: Subjects with panic symptoms had
      higher utilization rates for the services of psychiatrists and psychologists and
      for ambulance services than control subjects. Subjects who met criteria for panic
      disorder and who sought care specifically for panic symptoms generally accounted
      for the differences between the group with panic symptoms and the control group.
      The two groups differed little in barriers to access, but the control group
      reported that their medical insurance covered more types of services.
      CONCLUSIONS: Compared with control subjects, subjects with panic symptoms
      reported higher rates of health care utilization despite having less insurance
      coverage and experiencing similar barriers to access. The higher rate was due to
      increased utilization of health care by subjects who met criteria for panic
      disorder and to help seeking specifically for symptoms of panic.

PMID- 9255835
TI  - Principles for assessment of patient outcomes in mental health care.
AB  - With the dramatic changes that are occurring in mental health and substance abuse
      treatment systems, it is imperative that the field keep its focus on the patient
      and the patient's outcomes of care. Outcomes management systems that measure the
      processes of care, the patient's characteristics, and the patient's outcomes of
      care can be helpful in maintaining this focus. To facilitate the development of
      these systems, the Outcomes Roundtable, a group of mental health consumer,
      professional, service, and policy-making organizations, has articulated a set of
      12 broadly applicable principles of outcomes assessment. The principles call for
      outcomes assessments that are appropriate to the question being answered, that
      use tools with demonstrated validity and reliability and sensitivity to
      clinically important changes over time, and that always include the consumer
      perspective. In addition, the principles recommend outcomes assessments that
      create minimal burden for respondents and are adaptable to different health care
      systems, that include general health status as well as mental health status, and
      that include consumers' evaluation of treatment and outcomes. Outcomes assessment
      tools should quantify the type and extent of treatment, should include generic
      and disorder-specific information, and should measure areas of personal
      functioning affected by the disorder. Outcomes should be reassessed at clinically
      meaningful points in time. Outcomes assessment should use appropriate scientific
      design and representative samples and should examine outcomes of consumers who
      prematurely leave treatment as well as those who continue in treatment.

PMID- 9255836
TI  - Association between mood-stabilizing medication and mental health resource use in
      the management of acute mania.
AB  - OBJECTIVE: To better understand how mood-stabilizing agents other than lithium
      have changed treatment and outcomes in bipolar disorder, this study examined
      health service utilization among patients with acute mania who were being treated
      with a variety of regimens using mood stabilizers. METHODS: Demographic,
      clinical, and resource utilization data were collected from the records of 96
      inpatients with a discharge diagnosis of bipolar mania. Patients were categorized
      into four major treatment groups: lithium monotherapy, anticonvulsant
      monotherapy, treatment with multiple mood stabilizers, and treatment with no mood
      stabilizers. RESULTS: The mean +/- SD age of the sample was 50 +/- 12.3 years.
      Lithium was the most commonly prescribed antimanic agent, with 29 of the 96
      patients on lithium monotherapy, 17 on anticonvulsant monotherapy, 42 taking
      multiple mood stabilizers, and eight taking no mood stabilizers. The mean
      inpatient stay was significantly longer for patients on multiple mood stabilizers
      (30.3 +/- 20.7 days) than for those on lithium monotherapy (20.7 +/- 14.4 days),
      anticonvulsant monotherapy (17 +/- 9.3 days), and no mood stabilizers (17.3 +/-
      14.4 days). Patients who were not taking a mood stabilizer had a higher rate of
      leaving the hospital against medical advice than the other groups. Patients on
      anticonvulsant monotherapy had significantly more comorbid psychiatric illnesses
      than patients taking multiple mood stabilizers. Inpatient use of seclusion or
      restraint and of concurrent antipsychotic medications did not differ
      significantly between the treatment groups. Compliance with outpatient follow-up
      was poor in all treatment groups, and almost absent in the group taking no mood
      stabilizers. CONCLUSIONS: Changes in the pharmacological management of acute
      mania will have an impact on clinical outcomes and health resource utilization.

PMID- 9255837
TI  - A consumer-constructed scale to measure empowerment among users of mental health
      services.
AB  - OBJECTIVE: A scale to measure the personal construct of empowerment as defined by
      consumers of mental health services was developed and field tested. METHODS:
      After extensive development, pilot testing, and analyses, a 28-item scale to
      measure empowerment was tested on 271 members of six self-help programs in six
      states. Factor analyses were used to identify the underlying dimensions of
      empowerment. To establish the scale's reliability and validity, responses were
      factor analyzed, and other analyses were conducted. RESULTS: Analyses revealed
      five factors: self-efficacy-self-esteem, power-powerlessness, community activism,
      righteous anger, and optimism-control over the future. Empowerment was related to
      quality of life and income but not to the demographic variables of age, gender,
      ethnicity, marital status, education level, or employment status. Empowerment was
      inversely related to use of traditional mental health services and positively
      related to community activism. CONCLUSIONS: The findings set a framework for a
      clearer understanding of the imprecise and overused concept of empowerment. The
      scale demonstrated adequate internal consistency and some evidence for validity.
      Further testing must be done to establish whether it has discriminant validity
      and is sensitive to change.

PMID- 9255838
TI  - Computerized screening for psychiatric disorders in an outpatient community
      mental health clinic.
AB  - OBJECTIVE: This study examined the validity and utility of two types of computer
      administered versions of a screening interview, PRIME-MD (Primary Care Evaluation
      of Mental Disorders), in a mental health setting: one administered by desktop
      computer and one by computer using a touch-tone telephone and interactive voice
      response (IVR) technology. METHODS: Fifty-one outpatients at a community mental
      health clinic were given both IVR and desktop PRIME-MD and the Structured
      Clinical Interview for DSM-IV (SCID-IV), which was administered by a clinician,
      in a counterbalanced order. Diagnoses were also obtained from charts. RESULTS:
      Prevalence rates found by both computer interviews were similar to those obtained
      by the SCID-IV for the presence of any diagnosis, any affective disorder, and any
      anxiety disorder. Prevalence rates for specific diagnoses were also similar to
      those found by the SCID-IV except for dysthymia, obsessive-compulsive disorder,
      and panic disorder; the first two conditions were found to be more prevalent by
      the computer, and panic disorder was more prevalent by the SCID. Compared with
      the prevalence rates in the charts, the rates found by the computer were higher
      for anxiety disorders, particularly for obsessive-compulsive disorder and social
      phobia. Using the SCID-IV as the criterion, both computer-administered versions
      of PRIME-MD had high sensitivity, specificity, and positive predictive value for
      most diagnoses. No significant difference was found in how well patients liked
      each form of interview. CONCLUSIONS: Results support the validity and utility of
      both desktop and IVR PRIME-MD for gathering information from mental health
      patients about certain diagnoses.

PMID- 9255839
TI  - Dual diagnosis subtypes in urban substance abuse and mental health clinics.
AB  - OBJECTIVES: This study sought to determine rates of dual disorders (psychiatric
      and substance use disorders) in a population of low-income inner-city
      outpatients, to compare the rates in outpatient mental health and substance abuse
      treatment settings, and to examine the clinical usefulness of classifying
      patients with dual disorders into three subtypes. METHODS: A total of 57 low
      income urban residents receiving mental health treatment and 73 receiving
      substance abuse treatment were given semistructured clinical interviews to
      ascertain lifetime and concurrent DSM-III-R axis I disorders. Patients with dual
      disorders were classified into subtypes depending on whether their psychiatric or
      substance use disorder was caused by the comorbid disorder or whether both
      disorders existed independently. RESULTS: Eighty-three patients had a lifetime
      history of dual disorders: 34 patients (60 percent) in the mental health settings
      and 49 (67 percent) in substance abuse treatment. Among the 83 with dual
      disorders, more than half had experienced symptoms of both disorders within the
      past year. Each of the disorders was considered primary (that is, no indication
      was found that one was caused by the other) for 24 patients in the mental health
      settings (71 percent) and 31 in the substance abuse treatment settings (63
      percent). CONCLUSIONS: In each type of treatment setting, nearly two-thirds of
      the patients met criteria for a lifetime diagnosis of a dual disorder. This high
      rate of comorbidity did not appear to be attributable to substance use causing
      psychiatric symptoms, or vice versa. The high rate suggests the need for greater
      integration of mental health and substance abuse treatment, regardless of
      setting.

PMID- 9255841
TI  - Substance use during sex and unsafe sexual behaviors among acute psychiatric
      inpatients.
AB  - A total of 239 acute psychiatric inpatients were interviewed about whether they
      used substances just before or during sex and whether they engaged in unsafe
      sexual behaviors while using substances. Nearly 40 percent of male patients and
      36 percent of female patients reported using alcohol at least once during sex in
      the previous six months. Among male patients a statistically significant
      association was observed between using crack during sex and two high-risk
      behaviors--inconsistent condom use and sex with a high-risk partner. Among female
      patients the use of alcohol before or during sex was significantly associated
      with the practice of receptive anal sex.

PMID- 9255840
TI  - Satisfaction of Vietnamese patients and their families with refugee and
      mainstream mental health services.
AB  - OBJECTIVE: The study examined levels of satisfaction with mainstream mental
      health services and specialized mental health services for refugees among
      Vietnamese psychiatric patients and their relatives. Demographic, diagnostic,
      symptomatic, and service-related issues that might influence satisfaction were
      investigated. METHODS: Eighty-six Vietnamese patients were identified from case
      notes of mainstream inpatient services (N = 31), mainstream community services (N
      = 7), and a specialized refugee treatment unit (N = 48). During an interview, a
      scale measuring satisfaction with treatment as well as measures of anxiety,
      depression, and posttraumatic stress disorder was administered to them. A
      modified satisfaction scale was administered to 56 relatives. RESULTS: Patients
      and relatives were, on average, moderately satisfied with treatment. Patients
      expressed greater satisfaction with the specialized treatment unit for refugees
      than with mainstream services, a finding that was not influenced by diagnostic
      differences or symptom levels at the time patients responded. Further analyses
      controlling for multiple comparisons revealed that the extent of the information
      provided and the ease of negotiating changes in treatment were the most salient
      variables in distinguishing satisfaction levels across the two types of treatment
      centers. Patients' fluency in English and their relatives' level of education
      were inversely associated with satisfaction scores, tentatively suggesting that
      the greater the ability of patients and their families to evaluate services, the
      less likely they were to express satisfaction with treatment. CONCLUSIONS:
      Specialized mental health services for refugees may be more acceptable to refugee
      populations than their mainstream counterparts, perhaps because better
      communication with patients and their families is possible in the specialized
      services. Patients and families who are in a position to evaluate services fully
      are more likely to be critical of treatments offered.

PMID- 9255842
TI  - Educational needs of families of mentally ill adults.
AB  - A total of 197 family members of mentally ill adults in Indiana responded to a
      survey about their preferences for family psychoeducation programs, including
      type of information, format, presenter, frequency and length of educational
      programs, setting, and cost. The findings of the survey, which was sent only to
      persons who were not members of the National Alliance for the Mentally Ill,
      indicated that family members throughout the state have consistent and persistent
      needs and clear preferences about educational programs. Of 11 educational topics
      listed, family members expressed the least interest in learning about their
      relative's substance abuse. They were ambivalent about whether to include
      patients in family education programs, but they clearly supported patient
      education.

PMID- 9255843
TI  - A consumer satisfaction survey of people with mental retardation and mental
      illness.
AB  - This study investigated consumer satisfaction among 98 members of the Thomas S.
      class action lawsuit in North Carolina, in which the court ordered implementation
      of habilitative and residential service plans. Class members have mental
      retardation, and most also have a mental illness. Before the court order, 83 of
      the consumers were inappropriately placed in state psychiatric hospitals; one
      year after, 82 were living in community residences. A survey at baseline and one
      year later indicated that consumers' satisfaction had increased significantly.
      They were more satisfied with where they lived, the food, and the level of
      freedom. They also felt that staff were more helpful, and that more staff were
      "nice" rather than "mean."

PMID- 9255844
TI  - A state mental health system with no state hospital: the Vermont plan ten years
      later.
AB  - The feasibility and desirability of closing Vermont's only state hospital have
      been debated for ten years. The author examines the current status of the state
      department of mental health's plan to close the state hospital and concludes that
      although closure would be feasible, it would not be desirable. It would reduce
      the tertiary capacity of the mental health care system and would limit care for
      severely and persistently mentally ill persons who resist treatment and who have
      few social resources.

PMID- 9255845
TI  - Voting by Israeli patients.

PMID- 9255846
TI  - Consent for psychotherapy.

PMID- 9255847
TI  - The wrong issue.

PMID- 9255848
TI  - The dangers of lead.

PMID- 9255849
TI  - U.S. Supreme Court upholds Kansas law allowing indefinite civil commitment of
      sexual offenders.

PMID- 9255850
TI  - 75 percent of insured Americans now enrolled in managed behavioral health care
      programs.

PMID- 9255851
TI  - Effects of subchronic treatment with valproate on L-5-HTP-induced cortisol
      responses in mania: evidence for increased central serotonergic
      neurotransmission.
AB  - The mechanisms underlying the acute and prophylactic antimanic properties of
      valproate have remained elusive. There are some reports that treatment with
      valproic acid may increase brain serotonergic neurotransmission in the rodent.
      This study was carried out in order to investigate the effects of subchronic
      therapy with valproate on central serotonin metabolism in manic patients. Toward
      this end, the authors examined plasma cortisol responses to 200 mg (orally) L-5
      hydroxy-tryptophan (L-5-HTP) in 10 manic patients both before and after
      subchronic treatment with valproate. Administration of L-5-HTP resulted in
      significantly increased cortisol responses both before and after treatment with
      valproate. The L-5-HTP-induced cortisol responses were significantly higher after
      treatment with valproate than before treatment. It is suggested that valproate
      may increase central serotonergic neurotransmission and that this stimulation may
      play a role in the antimanic effects of valproate.

PMID- 9255852
TI  - Antisocial traits in psychiatrically ill veterans without antisocial personality
      disorder: relationship to Axis I disorders and effects on functioning.
AB  - The prevalence of antisocial traits was investigated in a group of veterans who
      were in treatment at an out-patient psychiatric clinic and who did not meet
      diagnostic criteria for an antisocial personality disorder. Standardized DSM-III
      R interviews were used to diagnose Axis I disorders and antisocial personality
      disorders and traits. Frequencies of antisocial traits were compared between
      patients and controls as well as between diagnostic subgroups in the clinical
      population. Odds ratios were used to assess the effect of antisocial traits on
      several standardized measures of functioning. There was no overall difference in
      the dimensional measure of antisocial traits between the clinical and normal
      groups. There were trends for the frequency of individual traits to vary by Axis
      I diagnosis. The amount of antisocial traits (measured dimensionally) negatively
      affected measures of functioning for the overall clinical population. Different
      specific antisocial traits were associated with trends towards poorer functioning
      in the alcohol, major depression and post-traumatic stress syndrome subgroups. It
      is recommended that future research in the area of antisocial traits pay careful
      attention to the possible negative effects on functioning of subthreshold
      antisocial traits and also to Axis I comorbidity.

PMID- 9255853
TI  - Measurement of aggression in psychiatric patients.
AB  - This article analyzes, describes, and characterizes the methods used for
      measuring aggression in studies on psychiatric patients. The authors reviewed all
      studies published between 1985 and 1994 in seven major psychiatric journals and
      found 103 studies on adult aggression and 43 on childhood and adolescent
      aggression. Almost half (44.7%) of the adult studies and 23.3% of the child and
      adolescent studies did not use any structured instrument; the remainder used a
      total of 52 different instruments, indicating that the methodology in this area
      is not well established. The methods used for measuring aggression were mainly of
      three types: observational measures; self-report questionnaires; and structured
      chart reviews. Each of these tools is described herein, with special focus on
      reliability and validity. Overall the reliability of the various scales is high,
      but the empirical validity is rather poor. In choosing a suitable method for
      measuring aggression, researchers should take into account the direction of
      investigation (e.g. state vs. trait aggression, dynamic or biological aspects of
      aggression) and the target population. Practical suggestions in this regard are
      offered.

PMID- 9255854
TI  - Neuropsychological differences between alcohol-dependent and cocaine-dependent
      patients with or without problematic drinking.
AB  - The present study evaluated differences among three groups of substance abusers,
      abstinent for 1-5 months. One group was composed of 17 alcohol-dependent
      patients. The other two groups were composed of cocaine-dependent patients who
      scored below (n = 29) or above (n = 18) the median Michigan Alcoholism Screening
      Test (MAST) score for the cocaine-dependent group in total. The Shipley Institute
      of Living Scale was administered to all subjects. An ANOVA, with age as a
      covariate, revealed that the cocaine-dependent group with lower MAST scores
      exhibited statistically significant impairments on the Shipley abstraction
      subtest and on total IQ relative to the two other groups. There were no group
      differences on the verbal subtest. The abstraction and IQ deficits in the lower
      MAST score cocaine-dependent group could not be explained by decreased verbal
      abilities, a greater duration or frequency of cocaine use, or by a higher
      prevalence of Antisocial Personality Disorder. However, a chi 2 analysis revealed
      that this group contained more individuals who used cocaine in its 'freebase' or
      smoked form. Since the two cocaine-dependent groups were comparable in
      demographic and psychological characteristics, but had different levels of
      cocaine exposure, the results suggest that the decrements in abstraction scores
      reflect a cocaine-related effect.

PMID- 9255855
TI  - Affect recognition in schizophrenia: a function of global impairment or a
      specific cognitive deficit.
AB  - To investigate cognitive variables related to affect recognition in
      schizophrenia, 63 subjects with DSM-III-R diagnoses of schizophrenia or
      schizoaffective disorder were administered a test battery which included the Bell
      Lysaker Emotion Recognition Task (BLERT), Wisconsin Card Sorting Test (WCST),
      Wechsler Memory (WMS-R) and Adult Intelligence Scales (WAIS-R), Hopkins Verbal
      Learning Test, Gorham's Proverbs, and Continuous Performance Task (CPT).
      Coefficients revealed a moderate relationship between emotion recognition and
      WCST and CPT but no significant relationship with other test variables. Multiple
      regression analysis demonstrated that approximately one-third of the variance in
      BLERT scores could be explained by cognitive variables including the Digit Symbol
      Subtest, CPT, and Hopkins Verbal Learning Test. Other analyses demonstrated that
      subjects with moderate to severe affect recognition impairment had more
      perseverative errors, had fewer complete categories on the WCST and had more
      errors on the CPT. However, there were no significant differences on global
      measures of impairment such as WAIS-R IQs and Digit Symbol Substitution Test. The
      discussion focuses on deficits in affect recognition as a distinct feature which
      contributes to the heterogeneity of the disorder.

PMID- 9255856
TI  - The effect of language production manipulations on negative thought disorder and
      discourse coherence disturbances in schizophrenia.
AB  - This study was designed to test the following hypotheses about the mechanisms
      underlying language disturbances in schizophrenia: (1) negative thought disorder
      (reduced verbosity and syntactic complexity, increased pausing) reflects a
      deficit generating a discourse plan; and (2) discourse coherence disturbances
      (tangential responses, loss of goal, derailment, non-sequiturs, distractible
      speech) reflect a deficit maintaining a discourse plan. Thirty-nine participants
      with, DSM-III-R schizophrenia listened to two stories and answered a series of
      questions after each story. We manipulated two factors: (1) the presence of
      context before the stories (to influence generating a discourse plan); and (2)
      question type (structured vs. unstructured; designed to influence maintaining a
      discourse plan). Consistent with our hypotheses, low context was associated with
      less verbose and syntactically complex speech. In addition, patients produced
      more discourse coherence disturbances when responding to unstructured than when
      responding to structured questions.

PMID- 9255857
TI  - Agreement between face-to-face and telephone-administered mood ratings in
      patients with rapid cycling bipolar disorder.
AB  - We examined the reliability and level of agreement between the telephone and face
      to-face administration of two mood-rating scales (HIGH-SAD and SIGH-SAD) in
      patients with rapid cycling bipolar disorder (RCBD). Two clinicians administered
      the HIGH-SAD and SIGH-SAD to 14 outpatients with RCBD. Patients received
      consecutive phone and face-to-face mood ratings in a randomized order. Using a
      paired t-test, no significant differences were found when comparing HIGH-SAD and
      SIGH-SAD scores administered face-to-face and over the phone. There was a high
      correlation between the face-to-face and phone administration of both scales as
      measured by intraclass correlation (r = 0.94 for SIGH-SAD; r = 0.85 for HIGH
      SAD). Our results support the use of phone-administered mood ratings as a
      reliable and convenient method to monitor patients with RCBD.

PMID- 9255858
TI  - Schizophrenia as a chronic active brain process: a study of progressive brain
      structural change subsequent to the onset of schizophrenia.
AB  - Brain structural deviation is known to be present in chronic patients with
      schizophrenia when compared with normal age-matched individuals. While the
      assumption is that these differences are based on a neurodevelopmental
      disturbance, whether they are static or continue to change throughout the disease
      process remains unknown. The following report describes a prospective follow-up
      study of first episode cases of schizophrenic illness. Analyses of MRI
      evaluations on an approximate annual basis for a minimum of four years are
      presented on 50 patients and 20 controls. Computer-assisted image analysis
      measuring the volume of several brain regions, using the program ANALYZE (Mayo
      Clinic), was performed on all scans. Patients were compared with controls for the
      rate of change over time in size of structures. No differences were found for the
      volumes of the caudate nucleus, temporal lobes, or hippocampus; and no changes in
      the degree of cerebral laterality were detected. However, there was a significant
      difference in the rate of change in the overall volumes of left and right
      hemispheres (P < 0.0004 and 0.001, respectively), right cerebellum (P < 0.02) and
      area of the isthmus of the corpus callosum (P < 0.05). The left cerebral
      ventricle had significantly greater enlargement over time when measured on
      coronal slice sequences (P < 0.02), but was not detected by axial views. These
      findings suggest that a subtle active brain process may be continuing through the
      first few years of a schizophrenic illness causing greater than the normal adult
      cortical deterioration. Further studies using other methods of image analysis and
      over a longer period of time are needed to determine the course and nature of
      this biologic process.

PMID- 9255859
TI  - Progression of cerebroventricular enlargement and the subtyping of schizophrenia.
AB  - Several anatomic abnormalities in the brains of schizophrenics have frequently
      been reported. However, it remains unresolved whether such neuropathology is
      fully expressed and static at the onset of psychosis or whether further
      deterioration evolves during the course of illness. To address this important
      question, we obtained serial volumetric magnetic resonance images (MRI) of the
      cerebral ventricles of 18 patients with schizophrenic symptoms. Repeated blind
      measurements of total ventricular volume (TVV) revealed < 2% error of the
      segmentation method. Over a 2-3 year period, the rate of ventricular expansion
      (RVE) was 2.2 +/- 1.6 cm3/year in the patients and 0.7 +/- 0.6 cm3/year in
      controls. The RVE in the patients was not normally distributed, but clustered
      into two groups: a group similar to controls (n = 10; RVE, 0.9 +/- 0.5 cm3/year)
      and a group with a significantly greater rate of expansion (n = 8; RVE, 3.9 +/-
      0.7 cm3/year) (P < 0.001). These results suggest that there are at least two
      subpopulations within the schizophrenias: one with relatively static ventricles
      and another with progressively enlarging ventricles. At least two distinct
      etiologic processes may thus underlie the clinical presentation of schizophrenic
      symptoms. Factors which might influence ventricular expansion (neuroleptic
      compliance, alcohol and recreational drug abuse, and some clinical correlates)
      could not account for differences between groups.

PMID- 9255860
TI  - Seasonality and pituitary volume.
AB  - Pituitary volume in humans has been reported to change size in response to
      experimental manipulations of photoperiod, and to be increased during an episode
      of non-seasonal major depression. We wanted to determine whether pituitary volume
      changes either across the seasons or during an episode of winter depression.
      Nineteen patients with winter-seasonal affective disorder and 19 sex-, age-,
      height-, and weight-matched controls underwent magnetic resonance imaging of the
      pituitary gland in both winter and summer. Images were obtained using 0.7-mm
      contiguous slices and the areas of all slices were summed to compute the final
      volume for each gland. We found no main effects or interactions involving either
      diagnosis or season in our primary analysis. In a post-hoc analysis, we found a
      trend towards a season x gender effect (P = 0.06), such that pituitary volume
      increased slightly (+4.0%) across seasons in women, whereas it decreased slightly
      (-4.3%) across seasons in men. The results suggest that neither winter depression
      nor the change of seasons is associated with a significant change in pituitary
      size.

PMID- 9255861
TI  - Cerebral blood flow related to induction of a depressed mood within and out of
      the realm of attention in normal volunteers.
AB  - The effects of a depressed mood on regional cerebral blood flow (rCBF) were
      measured after a mood-induction procedure (MIP) in normal volunteers. The MIPs
      were administered 'within the realm of attention' and 'out of the realm of
      attention'. A modified Velten procedure, which consisted of tape-recorded self
      referent depressive statements, was used for mood induction. For the induction
      out of the realm of attention, a combination of dichotic listening and subliminal
      stimulation was used. A neutral induction procedure served as a control
      condition. CBF was measured with Tc-99m HMPAO single photon emission computed
      tomography (SPECT) with regard to 14 healthy female students. Scores on mood
      rating scales showed negative changes after both MIPs. Statistical analyses
      revealed lateralized changes in rCBF in the thalamus. Decreased thalamic CBF in
      the right hemisphere was demonstrated after both MIPs compared with the neutral
      induction condition. Moreover, hippocampal rCBF increased significantly, but only
      after induction out of the realm of attention. These findings suggest both
      hippocampal and thalamic involvement in the regulation of mood experience.

PMID- 9255862
TI  - 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for
      neuronal loss in the cingulate gyrus and the right striatum.
AB  - We compared 12 patients with obsessive-compulsive disorder (OCD) and six control
      subjects by 1H-magnetic resonance spectroscopy. Significantly lower relative N
      acetyl-aspartate (NAA) levels were found in the right striatum of OCD patients,
      as well as a decrease of anterior cingulate NAA that correlated with severity of
      illness. Age and sex were correlated to striatal NAA levels.

PMID- 9255863
TI  - Magnetic resonance brain imaging in women with obsessive-compulsive disorder and
      trichotillomania.
AB  - Magnetic resonance imaging of the brain was undertaken in women with obsessive
      compulsive disorder (n = 13), trichotillomania (n = 17), and healthy controls (n
      = 12). Caudate volume and ventricular-brain ratio (VBR) (variables that have
      previously been highlighted as abnormal in studies of OCD) were compared in the
      three subject groups and were correlated with neuropsychological and neurological
      soft sign findings. No significant differences were found between women with OCD,
      trichotillomania and normal controls on caudate volume or VBR. Decreased left
      caudate volume was significantly correlated with impairment on neuropsychological
      testing and with increased neurological soft signs. The negative findings here
      may indicate that in women with OCD and related disorders structural brain
      abnormalities are less obvious or less common than in men with these conditions,
      or they may reflect inadequate sensitivity of the brain measures employed.

PMID- 9255864
TI  - HLA class-I-specific NK receptors belong to two distinct molecular families and
      display inhibitory or activating function.

PMID- 9255865
TI  - HLA class-I-specific inhibitory receptor in human T lymphocytes: interference
      with T-cell functions.

PMID- 9255866
TI  - The CD94/NKG2C-type lectin receptor complex in recognition of HLA class I
      molecules.

PMID- 9255867
TI  - The role of natural killer cells in allograft responses to MHC antigens in the
      rat.

PMID- 9255869
TI  - Immunoglobulin superfamily inhibitory receptors: from natural killer cells to
      antigen-presenting cells.

PMID- 9255868
TI  - Role for NK-cell-associated Fas ligand in cell-mediated cytotoxicity and
      apoptosis.

PMID- 9255870
TI  - Inhibitory and activatory receptors for MHC class I molecules.

PMID- 9255871
TI  - NKRP1A and p40 molecules are involved in regulation of activation and maturation
      of human NK cells.

PMID- 9255872
TI  - NK receptors and signalling.

PMID- 9255873
TI  - Events in the adaptation of natural killer cell receptors to MHC class I
      polymorphisms.

PMID- 9255874
TI  - Ontogeny of NK cells and the bone marrow microenvironment: where does IL15 fit
      in?

PMID- 9255875
TI  - Outbreak of acute hepatitis A among homosexual men in East London.
AB  - We report an outbreak of hepatitis A among homosexual men. There was no
      indication of a common source outbreak or any connection with foreign travel. It
      is likely that infection was sexually acquired.

PMID- 9255876
TI  - Hepatitis A outbreak amongst intravenous amphetamine abusers in Finland.
AB  - This article describes a widespread outbreak of hepatitis A virus (HAV) infection
      amongst drug abusers in Finland. Although attempts to demonstrate the virus in
      amphetamines failed, the infection was assumed to be linked to intravenous use of
      the drug. The unusual mode of transmission prompted us to analyse possible
      atypical clinical features as well as the spread of the virus to the general
      population, nowadays practically without protective immunity. Serologically
      verified cases that occurred in Helsinki were interviewed, their hospital records
      were analysed and their contacts were serology tested. Amphetamine lots, as well
      as faecal samples from patients, were examined with RT-PCR. Detailed information
      was obtained from 238 subjects, among whom 131 admitted drug abuse and 67 cases
      were classified as secondary cases. Phylogenetic analysis of virus strains from
      HAV-infected cases suggested a common origin, and epidemiological observations
      linked it with particular lots of amphetamine. Three cases died, and 3 presented
      with severe clinical disease. Icterus was more common among i.v. drug abusers
      than others. Infection with hepatitis A virus was probably related to the faecal
      contamination of amphetamine associated with the transportation of the drugs in
      the gastrointestinal tract.

PMID- 9255877
TI  - HTLV-I seroprevalence in the Sultanate of Oman.
AB  - 2329 subjects (blood donors and patients) from various areas of the Sultanate of
      Oman were investigated for the presence of HTLV-I antibody by as enzyme
      immunoassay (EIA) method. 10 subjects (0.4%), including 9/1586 blood donors
      (0.6%) and 1/165 patients with sexually transmitted diseases (0.6%), were found
      to be EIA seropositive with a regional variation in seroprevalence of 0-14%. 6/9
      EIA seropositive samples from blood donors yielded 'indeterminate' results on
      Western immunoblot analysis (WBA). A much larger survey with additional
      confirmatory assays such as a radioimmunoprecipitation assay (RIPA), should
      provide a more conclusive picture of the prevalence of this retroviral infection
      in the Sultanate.

PMID- 9255878
TI  - The seroprevalence of HTLV-I in patients with ocular diseases, pregnant women and
      healthy volunteers in the Kanto district, central Japan.
AB  - HTLV-I has been shown to be related to the development of inflammatory diseases
      in various organs such as the eyes, lungs and joints. In south-west Japan where
      HTLV-I is highly endemic, the term 'HTLV-I associated complex' has been approved.
      To investigate the seroprevalence of HTLV-I in the Kanto district in central
      Japan, we have estimated the frequency of seropositivity to HTLV-I in 2,110
      patients with various ocular diseases and 2,683 pregnant women, in addition to
      5,336 healthy volunteers. Of the healthy volunteers, only 42 (0.79%) were
      seropositive, and the HTLV-I seroprevalence in pregnant women was also only
      16/2,683 (0.60%) which was almost equal to that in female healthy volunteers aged
      15-44 years (0.59%). In patients with various ocular diseases, however, there was
      significantly higher seroprevalence of HTLV-I (2.32%) compared with healthy
      volunteers in each sex (male: p = 0.0029; female: p = 0.000023). These results
      suggest that the seroprevalence of HTLV-I in the Kanto district is much lower
      than in south-west Japan. On the other hand, HTLV-I infection was shown to be
      correlated to ocular diseases also in the Kanto district. In particular, we found
      a higher seroprevalence of HTLV-I in patients with inflammatory ocular disease,
      such as endogenous uveitis, episcleritis, retinitis pigmentosa and degenerative
      choroiditis. This possibly suggests a causative role of HTLV-I in the development
      of these inflammatory ocular diseases also where HTLV-I is not endemic.

PMID- 9255879
TI  - pp65 antigenemia as a marker of future CMV disease and mortality in HIV-infected
      patients.
AB  - We retrospectively evaluated the role of pp65 antigenemia (AGM) as a marker of
      cytomegalovirus (CMV) disease and mortality in 241 HIV-infected patients with
      fever. Of 225 patients in whom CD4 count was available, 189 (84%) had counts
      below 100/microL and 209 (92.8%) below 200/microL, 149 patients had negative AGM
      (AGM-) and 92 had positive AGM (AGM+), AGM+ patients were at a more advanced
      stage of HIV disease, as evaluated by CD4 count (p < 0.001) and prior AIDS
      diagnosis (p < 0.001). Overall, 29 patients (12%) presented concomitant CMV
      disease (18 retinitis): 24 (26%) in the AGM+ group and 5 (3.3%) in the AGM- group
      (p < 0.001). AGM had a negative predictive value of 96.6% but a positive
      predictive value of 26% which increased to 65% if a cut-off of > 10 CMV-positive
      cells/10(5) leukocytes was considered. The cumulative rate of future CMV disease
      at 3 months was 0% in AGM patients, 3% in patients with AGM 1-10/10(5) and 36% in
      patients with AGM > 10/10(5). In a multivariate analysis, no antiretroviral
      therapy, AGM+ and CMV disease were independently associated with mortality. The
      role of AGM as a marker of present CMV disease is limited. However, quantitative
      AGM may select patients at a high risk of future CMV disease. In addition, AGM
      may be a marker of shorter survival in severely immunosuppressed HIV-infected
      patients.

PMID- 9255880
TI  - Advantage of polymerase chain reaction in the diagnosis of herpes simplex
      encephalitis: presentation of 5 atypical cases.
AB  - Four case of herpes encephalitis (HSVE) are described. The diagnosis was
      established by polymerase chain reaction (PCR) assay of cerebrospinal fluid
      (CSF). These reports illustrate different situations in the clinical management
      of this disease. PCR was considered useful in confirming the HSVE diagnosis in 3
      atypical cases, and in the differentiation between virologic failure and
      postinfectious encephalitis in a patient with recurrence of symptoms. A case with
      typical HSVE clinical findings is also reported where PCR was negative and a
      temporal lobe lymphoma was diagnosed at autopsy. This last case is representative
      of the utility of PCR in the management of other diseases mimicking HSVE.

PMID- 9255881
TI  - A clinical study of beta-haemolytic groups A, B, C and G streptococcal bacteremia
      in adults over an 8-year period.
AB  - All of the 88 episodes of beta-haemolytic streptococcal bacteremia (2.9% of all
      bacteremias) in adult patients during the years 1987-94 in a university hospital
      were reviewed. 38 bacteremias (43%) were caused by group A, 24 (27%) by group B,
      3 (4%) by group C, and 23 (26%) by group G beta-haemolytic streptococcal. There
      was a statistically significant increase in group A and decrease in group C and G
      bacteremias (p < 0.02) compared to an earlier 8-year period in the same hospital,
      although the total number of streptococcal bacteremias remained the same. The
      most common T types of group A streptococcal strains were T11 (26%), T28 (14%),
      T6 and T1 (11% each), and T12 (8%). Cardiovascular disease, skin lesions,
      malignancy, and alcohol abuse were the most common underlying conditions. The
      most usual types of infection were skin (47%) and respiratory tract infections
      (23%). The overall mortality was 16%. It was highest in group A (24%) and lowest
      in group C (0%), 38% of patients with pneumonia died. All streptococcal strains
      were sensitive to penicillin, vancomycin, and cephalosporins. 11% of group A and
      12% of all the strains had decreased sensitivity to erythromycin, 14 and 38% to
      tetracycline, and 0 and 2% to clindamycin, respectively.

PMID- 9255882
TI  - The role of household contacts in the transmission of group A streptococci.
AB  - The intrafamilial spread and recurrence of group A beta-haemolytic streptococci
      (GAS) infections was investigated. The evaluation was based on 114 patients and
      their families treated with penicillin for 5 days and followed for 1 month. GAS
      of the same T-type as that of the isolate from the index case were found in other
      family members in 33% of the families. Genetic finger-printing using RFLP was
      performed on 33 of the isolates. The mothers dominated among the index cases, 40
      patients experienced recurrences, 27 of them were clinical 28 recurrences
      occurred within 10 days after the end of treatment. Of 20 T-typed patients with
      early clinical treatment failures, infected family members were detected in 16
      families (p < 0.001). In 19% of the patients GAS could be isolated from the nose.
      These patients had more ill family members than did other patients. An extensive
      intrafamilial streptococcal spread was found. Most recurrences of GAS
      pharyngotonsillitis after penicillin treatment are probably due to "ping pong"
      infection from family members.

PMID- 9255883
TI  - Viridans streptococcal bacteraemia due to penicillin-resistant and penicillin
      sensitive streptococci: analysis of risk factors and outcome in 60 patients from
      a single cancer centre before and after penicillin is used for prophylaxis.
AB  - 60 patients with 60 viridans streptococcal bacteraemic episodes (42 due to
      penicillin-sensitive and 18 due to penicillin-resistant viridans streptococci)
      were analysed in a population of 12,185 admissions and 1,380 bacteraemic episodes
      during a 7-year period in a National Cancer Institute. The incidence of viridans
      streptococci among bacteraemias decreased from 11.5% in 1989 to 2.5% in 1995
      after penicillin was introduced for prophylaxis of febrile neutropenia in acute
      leukaemia in 1993. However, the proportion of penicillin-resistant viridans
      streptococcal bacteraemias increased from 0 in 1989 and 1990 before any
      prophylaxis was given, to 12.9-16.7% after quinolones were used for prophylaxis
      in 1991 and 1992, and to 44.4-81.8% in 1993-1995 after penicillin was added to
      the quinolones. Mortality rate was higher in the subgroup of penicillin-resistant
      viridans streptococcal bacteraemias (p < 0.05). Statistically significant risk
      factors in patients with penicillin-resistant (compared with penicillin
      sensitive) viridans streptococcal bacteraemia were: acute leukaemia (p < 0.03),
      high doses of cytarabine (p < 0.05), mucocutaneous lesions (p < 0.004),
      breakthrough bacteraemia during prophylaxis with ofloxacine plus penicillin (p <
      0.001). Multiple logistic regression analysis showed that only acute leukaemia
      (OR 2.05, CI 0.85-1.85, p < 0.00452) and penicillin-resistance (OR 0.71, CI 0.103
      4.887, p < 0.0209) were significant independent predictors of inferior outcome.
      Breakthrough bacteraemia during empiric therapy with vancomycine occurred in 5 of
      116 patients treated with vancomycine, and during therapy with ampicillin plus
      gentamicin in 6 patients of 18 treated.

PMID- 9255884
TI  - Antimicrobial resistance of invasive Streptococcus pneumoniae in Slovenia, 1993
      1995. The Slovenian Meningitis Study Group.
AB  - The susceptibility of 108 Streptococcus pneumoniae strains isolated from normally
      sterile body sites during 1993-1995 in Slovenia has been studied. Overall
      resistance to penicillin, erythromycin, trimethoprim-sulfamethoxazole,
      cefuroxime, cefaclor and chloramphenicol was 16.6, 0.9, 26.8, 0, 4.5 and 4.6%,
      respectively. All penicillin-resistant isolates (intermediate resistance) were
      susceptible to cefotaxime, ceftriaxone and vancomycin. Isolates less susceptible
      to penicillin were also significantly less sensitive to chloramphenicol, cefaclor
      and trimethoprim-sulfamethoxazole than penicillin-sensitive strains. Pneumococci
      isolated in children were significantly (p < 0.05) more resistant to trimethoprim
      sulfamethoxazole than those isolated in adults. The study demonstrated moderate
      resistance rate of S. pneumoniae to penicillin and trimethoprim-sulfamethoxazole
      and a low-level resistance rate to erythromycin, cefaclor and chloramphenicol. No
      straightforward correlation between overall consumption of antibiotics and
      antimicrobial resistance was found.

PMID- 9255885
TI  - Choice of an oral beta-lactam antibiotic for infections due to penicillin
      resistant Streptococcus pneumoniae.
AB  - The activity, pharmacokinetic and pharmacodynamic parameters of 5 oral beta
      lactams have been compared against 400 penicillin-resistant Streptococcus
      pneumoniae (PRSP) isolated in 9 European countries. All the data have been
      calculated for the highest recommended oral dosage in France. Amoxicillin was by
      far the most effective antibiotic when considering its intrinsic activity (96% of
      the PRSP inhibited at 2 mg/l), the inhibitory quotient (100% of the PRSP > 1 vs
      69.2% for cefuroxime) or a time above MIC > 40% which best correlates with
      clinical results (96% for amoxicillin vs < 25% for the cephalosporins).

PMID- 9255887
TI  - Antimicrobial resistance pattern and plasmid profile of Salmonella typhi isolated
      from an outbreak in Tehran province.
AB  - The antimicrobial resistance patterns and plasmid profiles of Salmonella typhi
      isolates from sporadic cases (n = 33) and an outbreak (n = 48) were compared. Of
      28 sporadic drug-resistant isolates, 24 (85.7%) were multiply resistant. The
      predominant antibiotic resistance pattern was TeCmSmSxTAp, which was also the
      most common pattern of the outbreak isolates. 13 drug-resistant strains isolated
      before the outbreak (46.4%) were able to transfer the whole resistance pattern or
      part of it to Escherichia coli K 12 by conjugation. Although 20 of the sporadic
      strains contained plasmid DNA, transferable R plasmids were only detected in 13
      (65%) of them. Among the outbreak strains, the rate of R plasmid transfer was
      92.3%, with only the TeCmSmSxTAp pattern transferred. Plasmid profiling and Hind
      III endonuclease digestion of plasmid DNA identified a 91.2 megadaltons (Mda)
      plasmid that was recovered from most of the outbreak isolates and from 4 strains
      collected before the outbreak. This plasmid coded for TeCmSmSxtAp and transferred
      the pattern of resistance in toto. The results indicate multidrug-resistant S.
      typhi as a potential cause of infection in the region.

PMID- 9255886
TI  - Intrahospital spread of vancomycin-resistant Enterococcus faecium in Sweden.
AB  - During a 17-week period vancomycin-resistant Enterococcus faecium (VRE) was found
      in clinical specimens from 4 in-patients. All bacterial isolates were
      phenotypically VanA, showing high-level resistance to vancomycin (MIC 256
      micrograms/ml) and teicoplanin (MIC 24-256 micrograms/ml). The corresponding gene
      (vanA) was detected with PCR in strains from 3 of the patients. Three patients
      had been hospitalized at the renal unit at Orebro Medical Centre Hospital (OMCH).
      The fourth patient, diagnosed in another hospital, had received treatment in the
      oncology unit at OMCH. All patients recovered without treatment specific for VRE.
      Isolates from 2 patients were indistinguishable by pulsed-field gel
      electrophoresis of genomic DNA. Genetically, these strains were related to the
      VRE isolates from the 2 other patients. Screening of hospital staff and other in
      patients for gastrointestinal carriage of VRE was negative. Glycopeptide
      resistant enterococci have not previously been found in OMCH. No new cases were
      identified during a 10-month follow-up period. Our cases represent the first
      nosocomial outbreak of VRE in Sweden.

PMID- 9255888
TI  - PCR on disseminated tuberculosis in bone marrow and liver biopsy specimens:
      correlation to histopathological and clinical diagnosis.
AB  - Disseminated tuberculosis with negative pulmonary findings is a diagnostic
      problem. Histopathological studies of bone marrow (BM) and liver (LV) biopsies
      are the most reliable methods for diagnosis in such cases; however, their
      sensitivity is limited. In this retrospective study, 41 BM and 7 LV paraffin
      embedded biopsy specimens from clinically (clinical response to antituberculous
      treatment after 6 months follow-up) and/or histopathologically diagnosed
      tuberculosis were analysed for the detection of Mycobacterium tuberculosis DNA by
      polymerase chain reaction (PCR). Two different primer sets, one based on the
      repeated IS6110 sequence of M. tuberculosis and the other based on the mtp40 gene
      region, were used for amplification. Histopathological and PCR studies were
      positive for M. tuberculosis in 12/41, and 30/41 in BM and 4/7, and 6/7 in LV
      biopsy specimens, respectively. As the control group, 17 BM biopsy specimens
      obtained from patients with a positive Mantoux skin test but no active
      tuberculosis were analysed. One BM biopsy out of 17 control cases was positive
      with PCR while none was consistent with TB histopathologically. In conclusion,
      PCR might be applicable and more reliable than histopathological studies for
      detection of tuberculosis in BM and LV biopsy specimens.

PMID- 9255889
TI  - Adenylate kinase activity in the cerebrospinal fluid of children with tuberculous
      meningitis and its relationship to neurological outcome.
AB  - Cerebrospinal fluid (CSF) adenylate kinase activity was determined in 88 children
      (mean age 32.6 months) at stage II (n = 40) and stage III (n = 48) tuberculous
      meningitis (TBM) at, or shortly after, the initiation of treatment, and at weekly
      intervals thereafter for the first month of treatment, and in 60 children (mean
      age 40 months) investigated for, but later considered not to have meningitis. CSF
      adenylate kinase activity in this latter group ranged from 0 to 1.27 u/l (mean
      0.59 u/l). Mean CSF adenylate kinase activity during the first week of therapy in
      children at stage II TBM (2.95 u/l; range 0-9.22 u/l) differed significantly (p =
      0.03) from that in children at stage III TBM (5.62 u/l; range 0-18.93 u/l). CSF
      adenylate kinase activity did not differ between children at stage II and stage
      III TBM during any of the 3 subsequent weeks. CSF adenylate kinase activity was
      not related to CSF cell count, total protein or glucose concentration or
      intracranial pressure at any point during the first month of treatment, but was
      related to CSF lactate during the first week of therapy (p = 0.001). Consecutive
      determinations of CSF adenylate kinase activity were available in 34 children.
      Although CSF adenylate kinase activity tended to increase or decrease in keeping
      with changes in clinical condition this was not always the case. The close
      relationship of CSF adenylate kinase activity and lactate concentrations suggests
      that adenylate kinase activity reflects hypoxic cerebral metabolism and it was
      unusual for children with increased CSF adenylate kinase activity at the time of
      diagnosis to be clinically normal on completion of 6 months of antituberculosis
      treatment. Any treatment modality which significantly reduced CSF adenylate
      kinase activity in children early in the course of TBM would probably be of
      clinical benefit to the patients.

PMID- 9255890
TI  - Risk factors for community-acquired pneumonia in children: a population-based
      case-control study.
AB  - Risk factors for community-acquired pneumonia were studied by collecting data
      from all pneumonia patients (n = 201) in a defined child population between 3
      months and 15 years of age during a surveillance period of 12 months, and from
      randomly selected healthy controls under 15 years of age (n = 250) from the same
      area. A structured questionnaire was used, with 409 (176 patients and 233
      controls) families responding in total. The chi-square test, and the univariate
      and multivariate logistic regression analyses were used. The confounding effects
      of gender, age and place of acquisition were standardized, and the possible
      interactions between these variables and each individual risk factor were
      calculated. In the risk factor analysis, the responders were classified into 2
      age groups: under 5 years and 5-14 years of age. In children under 5 years of age
      the significant risk factors were a history of recurrent respiratory infections
      during the past year [odds ratio (OR) 5.5], a history of wheezing episodes (OR
      5.3), and a history of otitis media and tympanocentesis before the age of 2 years
      (OR 3.6). In the older children, the significant risk factors were a history of
      recurrent respiratory infections during the previous year (OR 3.0), and a history
      of wheezing periods at any age (OR 2.1). To sum up, a susceptibility to
      respiratory infections was found to be significantly associated with community
      acquired pneumonia, and no interactions with age, gender or place of acquisition
      were significant. This trend was reflected by a history of wheezing and that of
      acute otitis media.

PMID- 9255891
TI  - Adenosine deaminase activity in the aetiological diagnosis of community-acquired
      pneumonia.
AB  - A prospective study was undertaken to assess the usefulness of serum adenosine
      deaminase (ADA) activity in the aetiological diagnosis of 75 patients (mean age
      58 years) with community-acquired pneumonia who required hospitalization.
      Measurements of ADA were also carried out in 35 healthy subjects (mean age 52
      years). The serum ADA activity in patients with typical bacterial pneumonia (TBP)
      was 21 +/- 7 IU/l and in controls 22 +/- 9 IU/l. In 43 patients with atypical
      pneumonia (AP), ADA levels (43 +/- 23 IU/l) were significantly higher than in the
      previously related groups (p < 0.001). Analysis within the group of atypical
      pneumonia showed significant differences for infections caused by Coxiella
      burnetii (61 +/- 19 IU/l, p < 0.001), Mycoplasma pneumoniae (44 +/- 26 IU/l, p <
      0.001) and Legionella pneumophila (39 +/- 15 IU/l, p < 0.05), as compared with
      patients with bacterial pneumonia and normal control subjects. We conclude that
      serum ADA in patients with community-acquired pneumonia requiring hospitalization
      may provide useful additional diagnostic information on the aetiology of
      pulmonary infection.

PMID- 9255892
TI  - Amniotic fluid leukocytes and leukocyte esterase activity in parturients
      delivered by caesarean section.
AB  - Amniotic fluid specimens from parturients undergoing caesarean delivery were
      examined for leukocytes and leukocyte esterase activity, as well as for amniotic
      fluid bacteria and mycoplasmas by cultivation. The aim of this study was to
      evaluate the intrauterine environment in noninfected parturients and the
      associations between leukocyte test results, amniotic fluid microbial
      colonization and postcaesarean endometritis. Samples were obtained by direct
      aspiration at operation from 289 parturients with no clinical intrauterine
      infection. Among the total study population, leukocytes were found in 41% of the
      amniotic fluid samples by Gram staining and in 39% of the samples by the
      leukocyte esterase activity test. Leukocytes and leukocyte esterase activity were
      observed significantly more often in the amniotic fluids of parturients
      undergoing operation after onset of labour or ruptured membranes compared with
      those operated upon with intact membranes and no labour (p < 0.0001 and p <
      0.0001). Of 255 amniotic fluid cultures, microbial colonization was observed in
      82 (32%) parturients. Positive results in the leukocyte tests were associated
      significantly with amniotic fluid microbial colonization among parturients who
      underwent operation with intact membranes, or who underwent operation after
      rupture of the membranes and had cervical dilatation of < 5 cm at the operation
      (Gram stain: p < 0.0001; leukocyte esterase: p < 0.003). If cervical dilatation
      was > or = 5 cm, no such association was observed. In the population studied,
      endometritis developed in 2% and 4% of the parturients with positive test
      results. Thus, neither the presence of leukocytes nor detected leukocyte esterase
      activity were predictive of subsequent postoperative endometritis. In the
      detection of amniotic fluid microbial colonization, the tests functioned best in
      non-laboring parturients with intact membranes and in those operated on at the
      early stage of labour.

PMID- 9255893
TI  - Influence of low dose ciprofloxacin on microbial colonization of the digestive
      tract in healthy volunteers during normal and during impaired colonization
      resistance.
AB  - Ciprofloxacin in low doses is, in volunteers, effective for decontaminating the
      digestive tract [elimination of aerobic Gram-negative bacilli (GNB)] without
      disturbing colonization resistance. Before using this concept in neutropenic
      patients, we investigated if a low dose quinolone is still effective when the
      colonization resistance is disturbed by another antimicrobial agent.
      Ciprofloxacin 20 mg daily was effective in eliminating Gram-negative bacilli from
      the digestive tract in 4/5 volunteers, in 1 volunteer the GNB persisted in low
      concentration. No colonization with exogenous resistant GNB occurred. Following
      impairment of colonization resistance by addition of clindamycin 300 mg daily,
      3/5 volunteers became colonized by spontaneously acquired exogenous GNB resistant
      to ciprofloxacin. We conclude that selective decontamination with a quinolone in
      low dosage cannot be recommended in neutropenic patients because there is, in the
      case of disturbed colonization resistance, a real risk of acquisition of
      quinolone-resistant strains.

PMID- 9255894
TI  - Fungemia in cancer patients undergoing chemotherapy versus surgery: risk factors,
      etiology and outcome.
AB  - 26 patients with fungemia and cancer treated with chemotherapy (group A) were
      compared to 25 patients with fungemia and cancer treated with surgery (group B),
      to assess differences in etiology, risk factors and outcome. Candida albicans was
      responsible for 42% of fungemias in group A, and for 92% of fungemias in group B
      (p < 0.005). Breakthrough fungemia occurring during antifungal prophylaxis
      appeared in 46.6% of group A vs 12% of group B (p < 0.02). There was significant
      difference in outcome between the groups: 20% of patients after surgery vs 7.7%
      of those after chemotherapy died from fungemia (p < 0.04). Most common risk
      factors recorded in both groups were catheter insertion and previous therapy with
      broad spectrum antibiotics.

PMID- 9255895
TI  - Chronic intestinal infection due to subgenus F type 40 adenovirus in a patient
      with AIDS.
AB  - A case of chronic intestinal infection due to adenovirus type 40 lasting for 13
      months in a patient with AIDS is described. Adenovirus particles were detected by
      electron microscopy in biopsy samples taken from the duodenum 3 months after the
      onset of diarrhoea. The virus was identified as adenovirus type 40 in stool
      samples by ELISA monoclonal antibodies to adenovirus group antigen (MAd-g2) and
      types 40 and 41 (MA 40-1 and MA 41-1). No other enteropathogens were found. These
      data support a causal relationship between adenovirus 40 and the gastrointestinal
      symptoms of the patient. This is the first reported case of intestinal infection
      caused by adenovirus type 40 in a patient with AIDS.

PMID- 9255896
TI  - Fatal Listeria meningitis, endocarditis and pericarditis in a patient with
      haemochromatosis.
AB  - A 65-year-old man with primary haemochromatosis was admitted because of fever and
      confusion. He was found to have bacteraemia and meningitis due to Listeria
      monocytogenes. Treatment with ampicillin plus tobramycin was instituted, and
      despite an initial improvement, the patient experienced an unfavourable course
      and died. At postmortem examination, tricuspid valve endocarditis and purulent
      pericarditis with tamponade were detected. Listeria monocytogenes grew in the
      culture of the pericardial fluid. Documentation of Listeria monocytogenes
      pericarditis is extremely rare, and data on the patient described and on seven
      published cases are reported.

PMID- 9255898
TI  - Pleural empyema caused by Leuconostoc spp.
AB  - A rare case of pleural empyema caused by Leuconostoc spp. is reported. The
      patient was treated successfully with clindamycin. To our knowledge this is the
      first reported case of pleural empyema caused by Leuconostoc spp. In a patient
      with characteristic predisposing factors, such as a serious underlying disease,
      previous vancomycin therapy and thoracic access device. Our case illustrates that
      Leuconostoc spp. can cause pleural infection as further evidence of its human
      pathogenicity.

PMID- 9255897
TI  - Leuconostoc spp. septicaemia in a child with short bowel syndrome.
AB  - Septicaemia caused by the vancomycin-resistant Gram-positive bacteria Leuconostoc
      spp. is uncommon. We report a case of Leuconostoc spp. septicaemia in a child
      with short bowel syndrome fed through a central venous catheter and a
      gastrostomy. Leuconostoc spp. were isolated from several blood cultures. Despite
      several courses of antibiotics the fever continued and her condition
      deteriorated. After removal of the thrombotized central venous catheter her
      condition improved. Leuconostoc spp. was isolated from the thrombotic masses.

PMID- 9255899
TI  - Escherichia vulneris in a Danish soccer wound.
AB  - Escherichia vulneris was isolated from an infected soccer wound, a finding which
      has not apparently been described in Europe before, but by questioning Danish
      clinical microbiological laboratories a further 12 cases were discovered.
      Treatment with simple debridement and cefuroxime quickly eradicated the bacteria
      in our case.

PMID- 9255900
TI  - Isolation of Helicobacter pullorum from patients with enteritis.
AB  - Helicobacter pullorum, recently described as sp. nov., is commonly isolated from
      asymptomatic poultry. Two cases of human enteritis associated with H. pullorum,
      one of them in an immunocompromised patient, are reported. Problems in the
      correct species identification by means of phenotypic and genotypic methods are
      discussed and for the first time a fatty acid pattern of Helicobacter pullorum is
      presented.

PMID- 9255901
TI  - Legionella jordanis pneumonia unresponsive to fluoroquinolones in a non
      immunocompromised host.
AB  - Legionella jordanis has seldom been reported as a cause of infection in humans.
      We describe a case of pneumonia due to L. jordanis that occurred in a non
      immunocompromised 74-year-old patient and failed to respond to a combination of
      ceftriaxone and ofloxacin. Cure was achieved only after an erythromycin-rifampin
      combination was started.

PMID- 9255902
TI  - Penicillium marneffei infection in a Swedish HIV-infected immunodeficient
      narcotic addict.
AB  - We report a case of Penicillium marneffei infection, acquired in Thailand, in a
      Swedish HIV-infected immunodeficient heroin addict. This is the first case of
      penicilliosis marneffei diagnosed in Sweden. The patient had fever without focal
      symptoms. Cultures from bronchoalveolar lavage fluid and a mediastinal lymph node
      yielded the dimorphic fungus Penicillium marneffei. Treatment with amphotericin B
      followed by itraconazole was successful. Penicillium marneffei infection should
      be considered in HIV patients with fever who have visited Southeast Asia,
      especially northern Thailand and southern China.

PMID- 9255903
TI  - High proportion of multi-drug resistant Mycobacterium tuberculosis in Saudi
      Arabia.

PMID- 9255904
TI  - Diagnosis of thromboembolic disease during infancy and childhood.
AB  - Thromboembolic disorders are frequent complications in pediatric patients and the
      incidence seems to rise. Adult guidelines for thromboembolism do not hold for
      children because there are many age-related features. Congenital prethrombotic
      disorders play a major role in the pediatric population and activated protein C
      (APC) resistance is also the most frequently encountered problem. Acquired risk
      factors in children are central venous line thrombosis with serious
      complications, cardiac diseases such as cardiomyopathies, prosthetic heart valves
      and aneurysms, renal vein thrombosis, and nephrotic syndrome. Renal vein
      thrombosis primarily affects newborns. Children with the antiphospholipid
      antibody syndrome also have thromboses although less frequent than adults, but
      systemic lupus erythematosus is associated with a high incidence. Acute
      lymphoblastic leukemia is frequently associated with thrombosis in children,
      especially when complicated by APC resistance. The greatest risk of thrombosis in
      children is during the neonatal period, and again congenital prethrombotic states
      and catheter placement play a major role. The clinical manifestations in children
      reflect the site of the thrombosis and extensive laboratory evaluations and
      advanced diagnostic procedures must be employed to diagnose the thrombotic
      events.

PMID- 9255905
TI  - Molecular and functional properties of fetal plasminogen and its possible
      influence on clot lysis in the neonatal period.
AB  - The blood fibrinolytic system essentially consists of proteolytic enzyme
      activation processes leading to the formation of the fibrin-degrading enzyme
      plasmin. It is thus the counterpart of the blood coagulation system. It differs
      physiologically in newborns compared with adults. In newborns, the plasma levels
      of plasminogen, the inactive plasmin precursor, are relatively low, and a
      correlation between maturity and plasminogen levels is observed. Newborn
      plasminogen has been purified, characterized, and compared with adult plasminogen
      and does exist in a fetal form with an increased concentration of sialic acid,
      similar to fetal fibrinogen. We review the molecular and functional properties of
      fetal plasminogen and its possible influence on clot lysis and thrombolytic
      therapy in the neonatal period.

PMID- 9255906
TI  - APC resistance in childhood thromboembolism: diagnosis and clinical aspects.
AB  - Few studies of activated protein C resistance (APCR) and thromboembolism in
      childhood have been published. In the majority of childhood thromboses reported,
      the factor V Leiden mutation was associated with venous thromboses; however, one
      case report and three studies described arterial thromboembolism in infants and
      children due to the common mutation in the factor V gene. In one neonate purpura
      fulminans occurred, and heparin-induced thrombocytopenia type II was additionally
      documented. Two case reports and seven of nine studies reported associated
      clinical conditions together with inherited coagulation disorders. In three
      studies homozygous patients were mentioned. There are few studies describing the
      interaction between APCR and coagulation or the fibrinolytic system in
      symptomatic and nonsymptomatic infants. Compared with healthy brothers or sisters
      and a healthy age-matched control group, thrombin generation, D-dimer, PAI-1
      activity, and t-PA antigen were found clearly elevated in children with APCR. In
      addition, infants and children with the Arg506-to-Gln mutation in the factor V
      gene showed significantly increased thrombomodulin concentrations along with
      normal protein C activities compared with relatives and healthy controls. No
      difference was recorded in these studies between heterozygous infants and
      children without vascular occlusion and patients who previously had suffered from
      thromboembolism. Until long-term data are available for the treatment of patients
      with APCR, such children should be treated in the same way as patients with
      deficiencies of protein C, protein S, or antithrombin.

PMID- 9255908
TI  - Thromboembolic risks and complications in nephrotic children.
AB  - The identification of many biologic anomalies is progressively realized in
      nephrotic children, thanks to adult studies and to scientific advances. The
      number of anomalies and the intensity of alterations vary from one patient to
      another and during flare-ups in the same patient. Their severity is usually a
      function of the severity of the nephrotic syndrome (NS). The responsibility of
      each anomaly per se in triggering thrombotic complications is not yet known and
      today it is understood that the coexistence of several factors is necessary to
      induce these complications. Thus, the NS presents a true model because it can
      gather multiple thrombogenic anomalies. It might be more satisfying to
      characterize all of the mechanisms that could be responsible for a thrombosis
      rather than to assay all of the biologic components in one patient. When the main
      balances during the childhood NS are broken-pro- versus anticoagulant forces, pro
      versus antifibrinolytic forces, platelet/vessel wall interactions-one cannot
      evaluate with accuracy the possible impact of acquired interrelations such as a
      decrease of antithrombin versus an increase of protein C. Among the present
      unknown factors, a major one is related to the effects, if any, of the
      proteinuric factor (recently discovered) on the vascular endothelium and the
      central question is: would it be capable of changing the thromboresistant
      phenotype to a thrombogenic one? No absolute correlation has been found between
      the many biologic abnormalities and the occurrence of thromboembolic (TE)
      complications. However, it is of great interest to have the best evaluation of
      the TE risks in nephrotic children. The criteria that are commonly used are:
      albuminuria, and plasma levels of fibrinogen and antithrombin. One can suggest
      adding to these criteria the D-dimer assay, a molecular marker of coagulation
      activation, and the factor V Leiden workup because it represents a genetic
      predisposition for TE complications. As far as prevention of TE complications is
      concerned, the standard but basic guidelines of nephrotic patients must be
      followed. Furthermore, vitamin K antagonists should be administered as soon as
      the risk criteria are gathered, but only after a careful evaluation of the
      benefits/risks ratio. As to the treatment of TE events, one should follow the
      present recommendations for children. A better future regarding prevention of TE
      accidents is based not only on the necessity of multicentric prospective studies
      but also on basic research that will allow discovery of the "primum movens" of
      childhood NS.

PMID- 9255907
TI  - Homozygous type I plasminogen deficiency.
AB  - Homozygous type I plasminogen (Plg) deficiency has not been described in human
      subjects so far. Ligneous conjunctivitis is a rare and unusual form of chronic
      pseudomembranous conjunctivitis of unknown etiology. Here we report for the first
      time on homozygous type I Plg deficiency in three unrelated female patients who
      suffered from ligneous conjunctivitis and additional pseudomembranous lesions of
      other mucous membranes. The disease is caused by massive fibrin depositions
      within the "extravascular space" of mucous membranes because of absent clearance
      by plasmin. Infusions of albumin, fresh frozen plasma, or Lys-plasminogen (Lys
      Plg) into two of the three patients revealed normal Plg activation capacity in
      these patients. The absence of fibrinolytic activity could therefore be shown to
      be due to Plg deficiency. Similar studies in the third patient have not been
      completed. In the two patients studied so far, infusions of Lys-Plg resulted in
      prompt and adequate Plg recovery with a short half-life and high amounts of
      plasmin-antiplasmin complexes and D-dimer. One patient additionally revealed an
      inherited partial factor XII deficiency. Functionally, this factor XII deficiency
      did not interfere with Plg activation. However, there may be a pathway of Plg
      activation in this patient via the prekallikrein C1-INH system.

PMID- 9255909
TI  - Hemolytic uremic syndromes in childhood.
AB  - The hemolytic uremic syndrome (HUS) comprises hemolytic anemia, acute renal
      failure, and thrombocytopenia. It is the most frequent cause of acute renal
      failure in childhood. Ninety percent of the patients have a diarrheal prodrome,
      and are referred to as having typical HUS. Approximately 10% exhibit the so
      called atypical HUS. Typical HUS is caused by shigatoxin-producing Escherichia
      coli. The toxin, bound to the globotriosyl ceramide cell receptor and
      internalized, interferes with protein synthesis, predominantly of endothelial
      cells. The main target is the kidney, but nearly every organ system can be
      involved. The most common extrarenal involvement is damage to the central nervous
      system. The central event is probably an insult to the endothelial cell with
      consecutive loss of antithrombogenic properties. The von Willebrand factor,
      activation of platelets via platelet-activating factor, other growth factors
      (e.g., interleukins 1, 6, 8), nitric oxide, lipopolysaccharides, activated
      polymorphonucleated neutrophils, and the metabolites of the arachidonic acid
      cascade (e.g., prostaglandin I2) are believed to be involved in the pathogenic
      cascade. Controlled therapeutic trials with heparin, dipyridamole, aspirin, and
      urokinase have not been associated with improved outcome. Antibiotics have not
      yielded any benefit. Plasma infusions and plasma exchange appear to be
      efficacious, and are justified in cases of atypical HUS and thrombotic
      thrombocytopenic purpura. Binding of the toxin to the intestinal lumen, and
      thereby inhibition of enteral reabsorption, is under investigation.

PMID- 9255910
TI  - Essential thrombocythemia in childhood.
AB  - In addition to the criteria of the Polycythemia Vera Study Group, positive
      markers for essential thrombocythemia (ET) include spontaneous BFU-E,
      splenomegaly, and megakaryocyte morphology in bone marrow smears and biopsy
      material. The hematologic features of 11 reported cases of ET in childhood showed
      platelet counts in excess of 1000 x 10(9)/L in all, slight leukocytosis in 8, and
      splenomegaly in 9. The presenting thrombohemorrhagic manifestations in 8
      symptomatic cases were microcirculatory disturbances and transient neurologic
      ischemic attacks in 2, recurrent mucocutaneous bleedings in 6, and priapism in 1.
      There are no reports of ET in childhood complicated by microcirculatory
      disturbances at platelet counts below 1000 x 10(9)/L. Anagrelide and alpha
      interferon, which are non-leukemogenic agents for the reduction of platelet
      counts, may become the treatment of choice in childhood ET. Anagrelide is
      tolerated better than alpha-interferon. The potential leukemogenic drugs
      hydroxyurea and busulfan should be used cautiously and withheld as long as
      possible.

PMID- 9255911
TI  - Heparin therapy in pediatric patients.
AB  - Advances in tertiary care pediatrics have resulted in heparin being one of the
      most frequently prescribed drugs in children's hospitals. Heparin is essential
      for cardiopulmonary bypass, extracorporeal membrane oxygenation, renal dialyses,
      maintenance of patency of venous and arterial catheters, and treatment of
      thromboembolic events. Currently, protocols validated in adults are used for
      children. However, optimal use of heparin in pediatric patients will likely
      differ from adults because of age-dependent physiologic and pathologic
      differences in hemostasis that influence the activities of heparin. The following
      review summarizes the influence of age on heparin anticoagulant activities, and
      pharmacokinetics. The indications, monitoring, therapeutic range, factors
      influencing dose-response relationships, and side effects of heparin therapy in
      pediatric patients are discussed. Finally the current and future indications for
      low-molecular-weight heparins in pediatric patients are summarized. Multi
      centered, international clinical trials are urgently needed to assess and
      optimize the use of heparin in pediatric patients in a variety of clinical
      settings. Until these studies are completed, recommendations for adults provide
      guidelines for children.

PMID- 9255913
TI  - Male mortality differentials by socio-economic group in Ireland.
AB  - There is very little information on differences in mortality by socio-economic
      group in Ireland. Only one major study has been done in this area. That study was
      based on data for 1981 and confined to aggregate deaths for males aged between 15
      and 64. The objective of this paper is to extend the previous work along a number
      of important dimensions. Combined deaths data for males for the period 1986-1991
      are used, thereby allowing differentials to be estimated with more precision.
      Mortality differentials for males by cause of death are also explored using this
      data. Methodological issues associated with trend analysis are highlighted in the
      paper. There is some discussion on both causal relationships and policy
      implications arising from analysis of the data. The results confirm international
      trends in this area: poorer people have higher mortality relative to people in
      more advantaged circumstances.

PMID- 9255912
TI  - Intracerebral hemorrhage during fibrinolytic therapy in children: a review of the
      literature of the last thirty years.
AB  - In a retrospective study all available publications concerning children with
      thromboembolic disease and fibrinolytic therapy between January 1, 1964, and June
      30, 1995, were reviewed with regard to the occurrence of intracerebral
      hemorrhages (ICH). ICH was found in 14/929 patients analyzed. According to the
      age when thrombolytic therapy was performed, ICH was described in 2/468 children
      after the neonatal period, in 1/83 term infants; and in 11/86 preterm infants;
      10/40 preterm infants who were treated in the first week of life developed ICH.
      ICH during thrombolytic therapy in children is reported with the use of
      streptokinase, urokinase (UK), UK-activated plasmin, UK and plasminogen, and
      recombinant tissue plasminogen activator (rt-PA). The risk of developing an ICH
      from thrombolytic therapy seems to be low in children after the neonatal period
      and in term infants. Because of the high incidence of "spontaneous" ICH in
      preterm infants, it cannot be established whether the more frequently described
      ICH in these patients is a complication of thrombolytic therapy. In the absence
      of randomized trials this analysis may be helpful for decision making in children
      with thromboembolic disorders. However, the data have to be regarded with caution
      because of the summation of cases with different thromboembolic disorders,
      treatment with different substances in different dosages, and the retrospective
      study design that could lead to an underrepresentation of this complication.

PMID- 9255914
TI  - The black box in somatization: unexplained physical symptoms, culture, and
      narratives of trauma.
AB  - Stimulated by our clinical work with patients who manifest unexplained
      "somatoform" symptoms in the primary care setting, this article addresses a
      theoretical black box in our understanding of somatization: how does culture
      mediate severe stress to produce symptoms that cannot be explained by the
      presence of physical illness? Despite various problems in his explanation of
      hysteria, Freud broke new ground by emphasizing narratives of traumatic
      experiences in the development and treatment of unexplained physical symptoms.
      Except in anthropologically oriented cultural psychiatry, contemporary psychiatry
      has traveled away from a focus on narrative in the study of somatization. On the
      other hand, recent interest in narrative has spread across many intellectual
      disciplines, including the humanities and literary criticism, psychology,
      history, anthropology, and sociology. We operationally define narratives as
      attempts at storytelling that portray the interrelationships among physical
      symptoms and the psychologic, social, or cultural context of these symptoms.
      Regarding somatization and trauma, we focus on the ways that narrative integrates
      the cultural context with traumatic life events. In explaining the black box, we
      postulate that extreme stress (torture, rape, witnessing deaths of relatives,
      forced migration, etc.) is processed psychologically as a terrible, largely
      incoherent narrative of events too awful to hold in consciousness. Culture
      patterns the psychologic and somatic expression of the terrible narrative.
      Methodologically, we have developed some techniques for eliciting narratives of
      severe stress and somatic symptoms, which we illustrate with observations from an
      ongoing research project. In designing interventions to improve the care of
      somatizing patients, we are focusing on the creation of social situations where
      patients may feel empowered to express more coherent narratives of their prior
      traumatic experiences.

PMID- 9255915
TI  - Level of education, age of bearing children and mental health of women.
AB  - The present study examined the longitudinal relationship between women's mental
      health and both their level of education and age at which they had their first
      child. The women were divided into four groups depending on whether or not they
      had further education after leaving school and whether or not they had a baby
      before the age of 21. Longitudinal data collected over a 19-year period from this
      group of women suggested that psychological morbidity was relatively stable
      across this time span. Women who left school without proceeding to further
      education and those who became mothers before the age of 21 had higher
      psychological symptom scores than the other groups throughout this period. These
      two factors were associated with poorer mental health in an additive fashion. The
      women were also more likely to have separated from the father of their child and
      continued to be economically disadvantaged into mid-life.

PMID- 9255916
TI  - The legitimacy of grieving: the partner's experience at miscarriage.
AB  - Until quite recently the psychological and emotional effects of miscarriage on
      women were little understood. Research has now established that such effects are
      potentially very significant (Neugebauer and Kline, 1992; Leppert and Pahlka,
      1984; Lasker and Toedter, 1991), but the role and response of the male partner
      has received very little attention (Cummings, 1984). When acknowledged at all,
      the response of the male partner has generally been perceived to be largely as a
      provider of emotional support to his partner during and after her miscarriage. In
      this study, based on personal interviews with 20 partners of women in the north
      of England who experienced a recent miscarriage, a complex set of thoughts,
      feelings and considerable confusion about appropriate behaviour is revealed, to
      the extent that such males might feel it necessary to deny their own feelings of
      grief in a double-bind situation.

PMID- 9255918
TI  - The influence of socioeconomic status on health service utilisation by patients
      with AIDS in north Italy. The North-East Italian Group for Planning of AIDS
      Health Care.
AB  - Evidence for an association between socioeconomic status (SES) and health service
      utilisation (HSU) by patients with AIDS is examined using data for an Italian
      AIDS study population. A composite measure of SES which takes into account
      several key variables was developed using Multiple Correspondence Analysis. A
      classification of SES categories (high, medium-high, medium-low, low) was
      constructed and resource utilisation across the categories compared. The study
      population were patients with AIDS referred to 10 AIDS clinics in the study area
      in North-East Italy. A questionnaire survey was undertaken over the period
      January to June 1994, and was completed by 555 patients. Statistical analysis was
      conducted, using log-linear modelling, of health service utilisation (covering
      inpatient and day care) by SES categories, illness severity and HIV transmission
      route group. The analysis demonstrated that SES has a statistically significant
      association with variation in HSU, secondary in importance to severity of
      illness. This finding has important implications for future care planning for
      HIV/ AIDS in Italy, and potentially to other countries. Further research is
      needed to examine the relationship between SES and health service utilisation and
      costs in Italy and in other European countries.

PMID- 9255917
TI  - Healthy or druggy? Self-image, ideal image and smoking behaviour among young
      people.
AB  - Recent research indicates that there is an important, though complex,
      relationship between the social image of smoking and young people's self- and
      aspirational images. This study explored how young people see themselves (self
      image), how they would like to be (ideal image), and whether these differ
      according to age, gender and smoking status. Focus groups were used to elicit
      attributes which young people use to describe smoking and non-smoking images
      taken from fashion pages in youth magazines. These attributes were incorporated
      into a self-completion questionnaire which was administered to 897 young people
      from three age groups (12-13 years, 15-16 years and 18-19 years). The respondents
      rated their self- and ideal images on each of these attributes. Overall, there
      were few differences between the rank order of attributes by age, sex or smoking
      status. However, there were differences in the trait scores, with males and
      smokers tending to rate themselves more positively. The two traits which most
      clearly differentiated smokers and non-smokers were druggy/takes drugs (self- and
      ideal image) and healthy (self-image). It appears that smokers in general, and
      male smokers in particular, embraced certain dimensions of self- and aspirational
      image of which druggy, tough and tarty are signifiers. In contrast, the
      differences between female smokers and non-smokers were less consistent and
      differed with age. The implications for health promotion are discussed.

PMID- 9255919
TI  - Mutual influences of health and poverty. Evidence from German panel data.
AB  - While a large body of literature is concerned with the interplay of health and
      poverty in developing countries, comparable studies for developed countries are
      rare. Using data drawn from the German Socio-Economic Panel (GSOEP), this paper
      investigates the relationships between changes in relative income poverty, income
      changes and health-related quality of life in Germany, i.e. in an environment
      with nominally equal access to medical care, education and social security. A
      fundamental five-dimensional health concept is introduced and tested for its
      empirical performance. The background of the causal analysis is formed by two
      hypotheses, one regarding low income as a possible cause for poor health
      (prevention hypothesis) and the other assuming the opposite causal direction
      (deprivation hypothesis). By means of a descriptive analysis and a structural
      equations model, the existence of a more complex relational web between health
      and poverty is demonstrated.

PMID- 9255920
TI  - Validating a satisfaction questionnaire using multiple approaches: a case study.
AB  - We examined the validity of a questionnaire designed to measure the satisfaction
      of users of health services, using multiple tests of construct validity. Members
      of 2 health insurance plans in Geneva (Switzerland) answered a mailed
      questionnaire in 1992 (n = 1007) and 1993 (n = 1424). Response rates were 82%
      participants were 18-44 years old in 1992. The questionnaire included 22
      questions on satisfaction with medical care received during the past 12 months.
      Most items were adapted from the Patient Satisfaction Questionnaire. Four
      dimensions of satisfaction were measured: satisfaction with physician services (8
      items), communication (8 items), access (4 items) and insurance services (2
      items). Reliability (Cronbach's alpha) was satisfactory for the 2 former
      dimensions (alpha = 0.81 and 0.82 respectively), but lower than desired for the 2
      latter (alpha = 0.63 and 0.49 respectively). Participants who gave positive open
      ended comments had satisfaction scores 0.7-1.2 standard deviation units higher
      than participants who gave negative comments. Satisfaction scores were weakly
      correlated with satisfaction with private life, which indicates that the
      instrument did not simply measure a general tendency to be satisfied.
      Participants who said that care received in 1993 was worse than care received in
      1992 (retrospective assessment) experienced a decrease in satisfaction scores
      between 1992 and 1993 (prospective assessment). Most validation procedures
      provided independent but partial evidence for the validity of the instrument.
      Triangulation of several validation methods, as illustrated in this paper, may
      greatly improve the understanding of an instrument's properties.

PMID- 9255921
TI  - The ethics of euthanasia--attitudes and practice among Norwegian physicians.
AB  - The ethical guidelines of the Norwegian Medical Association strongly condemn
      physician participation in euthanasia and assisted suicide. A previous study on
      attitudes towards euthanasia in the Norwegian population, however, indicates that
      a substantial part of the population is quite liberal. This study explores
      Norwegian physicians' attitudes towards and experience with end of life dilemmas.
      Sixty-six percent of a representative sample of 1476 who received postal
      questionnaires responded. They confirmed that Norwegian physicians actually seem
      to hold quite restrictive attitudes towards euthanasia. Seventeen percent
      answered yes to a question of whether a physician should have the opportunity to
      actively end the life of a terminal patient in great pain who requests this help,
      while 4% agreed that the same could be done to a chronically ill patient with
      great pain and a poor quality of life who otherwise would have several more years
      to live. Six percent of the physicians had performed actions intended to hasten a
      patient's death, while 76% said that they at least once had treated patients even
      if they had felt that treatment should have been discontinued. A multiple
      logistic regression analysis showed that internal medicine specialists, surgeons
      and psychiatrists were significantly more restrictive than their colleagues in
      laboratory specialties, and that physicians educated abroad and those with
      negative attitudes towards patient autonomy had more liberal attitudes towards
      euthanasia, when gender and time since graduation from medical school were
      controlled for.

PMID- 9255923
TI  - The socio-spatial stigmatization of homelessness and HIV/AIDS: toward an
      explanation of the NIMBY syndrome.
AB  - A central element of community response to controversial human service facilities
      is the socio-spatial construction of stigma. This paper develops a conceptual
      framework for understanding the constitution and role of stigma in community
      rejection of human services, particularly those associated with homelessness and
      HIV/AIDS. Three facets of stigma concerning homelessness and HIV/ AIDS (non
      productivity, dangerousness, and personal culpability) are offered as a way of
      understanding the rising tide of community rejection toward human service
      facilities.

PMID- 9255922
TI  - People, places and coronary heart disease risk factors: a multilevel analysis of
      the Scottish Heart Health Study archive.
AB  - The Scottish Heart Health Study (SHHS), which recruited 5123 men and 5236 women
      between 1984 and 1986, was set up in part to investigate geographical variation
      in coronary heart disease in Scotland. Multilevel models are particularly
      appropriate for such hierarchical data, in which the individuals in the study can
      be represented by the lower level and the districts in which they live by the
      higher level. Multilevel models are presented for four coronary heart disease
      risk factors-diastolic blood pressure, cholesterol, alcohol consumption (defined
      both as units of alcohol consumed per week and as being a non-drinker) and
      smoking, for men and women separately. Significant district level variance was
      found for three out of the four variables studied, after controlling for
      socioeconomic and other variables considered at the level of the individual.
      These were for diastolic blood pressure, cholesterol and alcohol. Although the
      large majority of the variance was present at the individual level, the existence
      of significant variance at the district level is evidence that places may have a
      role in the distribution of coronary heart disease risk. Health policy aimed at
      reducing coronary heart disease should therefore consider the characteristics of
      places as well as individuals.

PMID- 9255925
TI  - Choosing a birth attendant: the influence of a woman's childbirth definition.
AB  - This study examines the impact of a woman's childbirth definition or beliefs on
      selecting either a Certified Nurse Midwife (CNM) or an obstetrician. The global
      hypothesis is that women who define birth as "natural" and "normal" are more
      likely to select a CNM than women who define it as "in need of medical
      attention." The quantitative and qualitative data were collected over a period of
      2 years from 200 pregnant women enrolled in a central New Jersey health
      maintenance organization (HMO) which had contracted with an independent group of
      CNMs to provide midwifery care to its clientele. The findings indicate that after
      controlling for risk-eligibility, women who define childbirth as "risky" and
      requiring technical medical intervention are more likely to select an
      obstetrician, while those who define it as "natural" and "normal" are more likely
      to select a Certified Nurse Midwife. Additionally, a number of social
      characteristics such as expectation of information, support from the baby's
      father, and a low desire for control over the birth process are related to
      selecting a CNM. Anticipated choice, measured at the first prenatal visit, is
      positively related to eventual choice, indicating that early pregnancy
      definitions accurately predict service usage. Factors affecting birth attendant
      selections for first-time mothers were somewhat different than those affecting
      non-first time mothers. Namely, non-first-time mothers were less influenced by
      perceived childbirth risks and expectations of information than first-time
      mothers. The implication of these findings is that by selecting providers who
      share their varying childbirth beliefs, women evaluate and endorse particular
      profession's practice style as most appropriate.

PMID- 9255924
TI  - The physical costs of AIDS caregiving.
AB  - Informal care has become an increasingly important element in the delivery of
      health and social services to people living with HIV disease or AIDS (PWAs), yet
      the provision of such care does not come without costs to the caregiver. Instead,
      caregiving imposes burdens that may compromise caregiver health. Common ailments
      among AIDS caregivers were examined with two waves of data from a diverse sample
      of informal care providers in Los Angeles and San Francisco (N = 642). Symptoms
      of poor physical health are markedly present among AIDS caregivers and are
      significantly associated with care-related demands and stressors. This stress and
      health relationship varies significantly between caregivers who are HIV
      seropositive and those who are seronegative. Care-related effects are more direct
      among seronegative caregivers who are perhaps less overwhelmed with the
      maintenance of their own health. For all caregivers studied, level of depression
      and prior physical health are strong correlates of these physical ailments.
      Implications of these results are discussed.

PMID- 9255926
TI  - Unplanned pregnancies in Harare: what are the social and sexual determinants?
AB  - A hospital-based study was undertaken in Harare, Zimbabwe to estimate the
      proportion of unplanned or unintended pregnancy among mothers who delivered at
      the referral hospital and to analyse their socio-demographic pattern and sexual
      relationships. A case-referent study design was used with systematic sampling of
      maternity records of mothers who had delivered. Interviews were performed before
      discharge using a semi-structured questionnaire. Mothers who reported that the
      index pregnancy was unplanned or unintended constituted the cases, and the
      referents were those reporting the pregnancy as planned. Out of 923 deliveries,
      41% were unplanned and 9% unwanted. The mean age of the mothers was 25 years and
      women aged 19 or below [Odds Ratio (OR) = 2.2, 95% CI = 1.5-3.2] and 35 or above
      (OR = 2.8, 95% CI = 1.7-4.6) were significantly more likely to present with
      unplanned pregnancy. Nulliparous women (OR = 2.4) and mothers with five or more
      pregnancies (OR = 8.2) had a significantly increased likelihood of the pregnancy
      being unplanned. Level of education in the mothers studied had no independent
      association to planning of pregnancy. Unemployed (OR = 14) and single (OR = 7.8),
      or divorced/separated/widowed (OR = 5.1) women as well as those with low income
      (OR = 2.1) and whose partner earned no income (OR = 2.2), were more at risk of
      unplanned pregnancy. Those living with their own parents despite being pregnant
      were also more likely to report an unplanned pregnancy. In conclusion, there are
      documentable social and reproductive factors underlying unwanted pregnancy. Risk
      factors for unplanned pregnancy form a pattern similar to those for maternal
      mortality. Thus unplanned pregnancy is a major indicator of the presence of
      factors known to increase the risk of maternal death. Policy makers and health
      education should address factors contributing to unplanned pregnancy and its
      prevention in order to prevent reproductive mortality and morbidity. The presence
      of those factors associated with unplanned pregnancy at booking or delivery
      should also alert service providers to the need for appropriate contraceptive
      counselling as part of post delivery care.

PMID- 9255927
TI  - Age- and sex-differentials in morbidity at the start of an epidemiological
      transition: returns from the 1880 U.S. Census.
AB  - This paper uses a new data set, the Public Use file of the 1880 U.S. Census of
      the Population, to examine national point prevalence rates of adult morbidity
      over the early phase of the United States epidemiologic transition. These
      historical data report health status at the individual level and allow the
      analysis of age and sex differentials in morbidity. Point prevalence rates of
      morbidity by major cause show that males generally had higher rates of morbidity
      and long-term disability than females, especially at mid-life and in old age. But
      large sex differences in the distribution of conditions by major cause occurred
      over two portions of the life course: in early adulthood and in old age. Age and
      sex differences in the distribution of adult morbidity reflected the health
      status divide of the communicable and degenerative conditions.

PMID- 9255928
TI  - AIDS-related knowledge, attitudes and behaviour among South African street youth:
      reflections on power, sexuality and the autonomous self.
AB  - Street children in South Africa are, in the main, between the ages of 11 and 17
      years. Rape, prostitution, sexual bartering and exchange, casual sex and romantic
      sexual relationships all occur in the experiences of young people who live and
      work on inner-city streets. In this study, the AIDS-related knowledge, attitudes
      and behaviour of 141 street youth, living in seven large cities in South Africa,
      were elicited in focus group discussions. At the time of the study, 79 boys (56%)
      were living in shelters run by nongovernmental and welfare organisations, while
      62 boys (44%) were sleeping "rough". The results, both qualitative and
      quantitative, indicated that the AIDS knowledge of South African street children
      was comparable to levels reported for groups of "hard-to-reach" youth in other
      parts of the world. Fear of HIV infection did not appear in a list of day-to-day
      priorities constructed by the children, a list dominated by survival concerns
      with food, money and clothes. However, more than half of the boys conceded that
      they engaged in sex for money, goods or protection, several boys indicated that
      they had been raped, and most reported being sexually active with "girlfriends",
      who themselves frequently engaged in transactional sex. The findings are
      interpreted in terms of the relationships between power dynamics surrounding race
      and age, and how they affect self-initiated controls over sexuality and sexual
      protection.

PMID- 9255929
TI  - How marginal is a "marginalised group"?

PMID- 9255930
TI  - Characterization of the infection of Aedes albopictus cell clones by Sindbis
      virus.
AB  - We have investigated the infection of Aedes albopictus (mosquito) cell clones by
      Sindbis virus. Variation in the multiplicity of infection (MOI) from ranges of 50
      0.00005 pfu/cell was determined to have no effect on the progression of the
      infection to high acute phase titer, suggesting that intracellular factors alone
      are responsible for the restriction of virus production seen as the infection
      enters the persistent phase: While persistently infected (over 1 year post
      infection) cell clones are morphologically indistinct from uninfected cells, they
      do display a uniform 30% reduction in growth rate compared with uninfected cells
      of the same clone. Using flow cytometry-based DNA content analysis, we found that
      persistent Sindbis virus infection induces distinct cytological effects on these
      cells, including an increase in apoptosis and polyploidy in one clone and cell
      cycle phase effects in another. Finally, the observation that the number of cells
      in persistently infected cell cultures which are productively infected closely
      approximates the number of cells dying by apoptosis prompted us to investigate
      the role that cell death may play in the maintenance of the persistent infection.
      Persistently infected cell cultures which were artificially induced into
      apoptosis by short 45 degrees C heat treatments do not display increased Sindbis
      virus production. This result does not support the hypothesis that infection
      sensitivity induced by random apoptosis in persistently infected cell cultures is
      responsible for the long-term maintenance of the persistent infection.

PMID- 9255931
TI  - Reinfection-induced increase of rubella persistently infected cells in a
      macrophage-like cell line.
AB  - The establishment and relevant characteristics of a long-term rubella persistent
      infected immortalised murine macrophage culture with a high proportion of
      persistent infected cells over uninfected is described. The high proportion of
      persistent infected macrophages was obtained through reinfection with the
      original virus. Prior to reinfection, 35-50% of the cells expressed viral
      antigen, 0.05-1.5% produced infective virus and extra-cellular virus was
      continuously produced with infective titers cyclically fluctuating between 10(2)
      and 10(7) TCID50/ml. After reinfection, the macrophages which expressed viral
      antigen and produced infective virus had increased to 75-90% and 30-45%
      respectively and extracellular virus was continuously produced with stable titer
      between 10(2)-10(3) TCID50/ml. Furthermore, in the reinfected culture no
      significant variation was observed in the percentage of cells expressing antigen,
      producing virus and in the titer of extracellular virus for longer than a year of
      passages.

PMID- 9255932
TI  - Recombinant fowlpox virus vaccines against Australian virulent Marek's disease
      virus: gene sequence analysis and comparison of vaccine efficacy in specific
      pathogen free and production chickens.
AB  - We have cloned and sequenced the glycoprotein genes gB, gC and gD of the
      Australian virulent Marek's disease virus (MDV) isolate Woodlands No. 1. The
      glycoprotein gB and gC sequences were identical to the homologs of other virulent
      MDV type 1 strains, and the glycoprotein gD sequence contained only one unique
      amino acid substitution. Recombinant fowlpox viruses (rFPVs) expressing the MDV
      glycoprotein genes were constructed and their efficacy as vaccines was evaluated
      in specific pathogen free (SPF) and production chickens. Vaccination with the FPV
      gB recombinant protected SPF chickens from Marek's disease mortality and tumour
      formation following challenge with virulent MDV Woodlands No. 1. The degree of
      protection from Marek's disease was dependent on the vaccine dose and route of
      inoculation. The rFPVs expressing gC or gD did not provide protection from
      Marek's disease. A rFPV expressing both gB and gC did not provide enhanced
      protection in comparison with the rFPV-gB alone. The rFPV-gB vaccine failed to
      protect commercial chickens from MD mortality and provided little protection from
      tumour formation in comparison with the commercial herpesvirus of turkey (HVT)
      vaccine. The failure to provide protection against MD may be related to the
      impact of maternally derived immunity to MDV and FPV and possibly the genotype of
      the chickens.

PMID- 9255933
TI  - Biologic effects of introducing additional basic amino acid residues into the
      hemagglutinin cleavage site of a virulent avian influenza virus.
AB  - We mutated the virulent avian influenza virus A/turkey/Ontario/7732/66 (H5N9)[Q-R
      R-R-K-K-R?G at the hemagglutinin (HA) cleavage site] to create a mutant, R(MO-0),
      with additional basic residues at this site (Q-R-R-R-R-R-K-K-R?G) by reverse
      genetics. When tested in chicken embryo fibroblast culture, this mutant showed
      reduced HA cleavability compared to that of the wild-type virus, but its plaque
      size was not appreciably altered. Virulence of the R(MO-0) virus in chickens was
      lower than that of the wild-type virus. These findings indicate that addition of
      excessive basic residues to an optimal recognition sequence for HA cleavage
      enzymes at the cleavage site is deleterious for HA cleavability. Previously, we
      showed that a mutant containing the suboptimal HA cleavage site sequence for
      cleavage enzyme recognition also had reduced HA cleavability and virulence
      compared to the wild-type virus. We conclude that the data presented here further
      substantiate our belief that the level of HA cleavability correlates with the
      degree of virulence when all other genetic characteristics are considered equal,
      irrespective of the mechanisms by which HA cleavability is reduced.

PMID- 9255934
TI  - Sequence analysis of equine adenovirus 2 hexon and 23K proteinase genes indicates
      a phylogenetic origin distinct from equine adenovirus 1.
AB  - We report the first nucleotide sequence data on equine adenovirus 2 (EAdV2) which
      corroborate on the molecular level that EAdV2 is distinct from equine adenovirus
      1 (EAdV1). Based on sequence homology with Eadv1 the hexon gene of Eadv2 was
      identified. HindIII restriction fragments containing the hexon and eight other
      viral genes were cloned into the plasmid pUC19 and the nucleotide sequence of the
      hexon and the 23K proteinase genes completely determined. Amino acid (aa)
      comparison of sequence fragments with published adenovirus (AdV) proteins
      identified the genes for the E1B/19K, IVa2, DNA polymerase, terminal protein,
      pVI, DNA binding and 100K proteins, usually with highest similarities to human
      AdV. The nine EAdV2 genes appeared to be in the same relative order as homologous
      genes of other AdV. The EAdV2 hexon was encoded between the minor capsid
      precursor protein pVI upstream and the 23K proteinase gene downstream and
      comprised 2712 nucleotides which translated into 903 aa residues. It was more
      closely related to the human AdV48 hexon with 71.6% identical and 82.7%
      functionally similar aa than to the EAdV1 hexon gene with 69.3% aa identity and
      80.7% functional similarity. The deduced aa sequence of the EAdV2 23K proteinase
      gene was 201 residues; it shared 59.7% identical and 75% similar aa residues with
      the bovine AdV3 23K proteinase as the closest relative. Phylogenetic analysis of
      the hexon and 23K proteinase genes indicated that EAdV2 does not share an
      immediate common ancestor with EAdV1 and other AdV.

PMID- 9255935
TI  - Characterization of a putative new HPV genomic sequence from a cervical lesion
      using L1 consensus primers and restriction fragment length polymorphism.
AB  - Various methods have been proposed for HPV detection and typing. Prevalence and
      distribution among types have varied depending upon the methods used and the
      populations studied. We have applied the polymerase chain reaction (PCR) followed
      by a Restriction Fragment Length Polymorphism (RFLP) analysis using the MY09/MY11
      primers for detection of HPV in cervicovaginal lavages obtained from 323 patients
      who were referred to our Clinical Department either for genital complaints or an
      abnormal PAP smear. We assessed (i) the prevalence of HPV and (ii) the
      reliability of RFLP-typing. For the latter, 35 PCR-HPV products were sequenced.
      HPV-DNA was detected in 40/197 (20.3%) patients with normal cytology 86/111
      (77.5%) with LSIL and 11/15 (73.3%) with HSIL. HPV-16 was the most common type
      detected in normal cervical cytology samples (10/40, 25%), whereas HPV 16 and 18
      were detected in 36/97 (37.1%) of the LSIL and HSIL patients, evidencing the
      presence of these high-risk HPV types not only in malignant conditions. Results
      obtained after partial nucleotide sequencing confirmed the results obtained by
      RFLP analysis. In this study, a putative new HPV fragment (GA6053) was
      identified. Its closest homology to other known HPV types is 73.8% to HPV-62,
      73.0% to HPV-61 and 67.7% to HPV-18. The use of degenerate primers, in
      conjunction with RFLP, proved to be a reliable method for HPV detection and
      typing.

PMID- 9255936
TI  - Differential effect of modified capped RNA substrates on influenza virus
      transcription.
AB  - The RNA-dependent RNA polymerase of influenza virus transcribes messenger RNA
      through a unique cap scavenging mechanism. Viral enzyme binds to the cap
      structure of host mRNA, cleaves the molecule 9-15 bases downstream of the cap,
      and uses the short capped oligonucleotide as a primer for mRNA synthesis.
      Previously, we have shown that the viral polymerase can efficiently bind capped
      RNAs shorter than 9 nucleotides in length, but the viral enzyme can not utilize
      these RNAs as primers. For this reason, these short capped oligonucleotides are
      potent inhibitors of influenza virus transcription. In these studies, it is now
      shown that short capped oligomers inhibit capped-RNA dependent transcription at
      the initial step of cap binding. In contrast, low concentrations of these short
      capped RNAs can actually stimulate viral transcription primed with high
      concentrations of the dinucleotide ApG. Another capped RNA derivative containing
      phosphorothioate oligonucleotides was also investigated as a potential polymerase
      inhibitor. This longer capped RNA was able to bind to the polymerase, but could
      not be cleaved to primer length by the enzyme associated endonuclease. Thus, the
      capped phosphorothioate RNA inhibited cap-primed transcription at the step of cap
      binding. However, in contrast to the short capped oligonucleotide, it also
      inhibited ApG primed viral transcription.

PMID- 9255937
TI  - Genetic characterization and phylogeny of Andes virus and variants from Argentina
      and Chile.
AB  - Andes virus, one of five hantaviruses known to cause hantavirus pulmonary
      syndrome (HPS), emerged in 1995 in southwestern Argentina (Lopez et al. (1996)
      Virology 220, 223-226). The complete nucleotide sequence of Andes virus S genome
      segment was determined and compared with sequences of viral RNAs in autopsy
      tissues of more recently reported HPS cases from southwestern Argentina and south
      of Chile (cases ESQ H-1/96 and CH H-1/96). Andes virus S segment was found to be
      1876 nucleotides in length and to encode the nucleocapsid protein (N), 428 amino
      acids in length. S segment analysis also revealed a long 5' non-coding region
      (547 nucleotides) which displays three copies of an octanucleotide sequence
      repeat. Comparisons of S segment sequences of ESQ H-1/96 and CH H-1/96 (82% of
      the entire genome sequence) with the corresponding sequences of Andes virus
      revealed identities of 97.2% and 98.5%, respectively. Sequence motifs identical
      and in the same positions as exhibited in Andes virus 5' non-coding region were
      found in both, ESQ H-1/96 and CH H-1/96 sequences. Three genome fragments of the
      M segment sequence of the viruses (representing approximately 34% of the entire
      sequence) were also analyzed. Comparisons of S and M segment sequences of Andes
      virus with the corresponding sequences of ESQ H-1/96 showed S and M segment
      identities which differ by less than 1.4%. Andes virus and CH H-1/96 have S
      segments that differ by 1.5% from one another while their M segment fragments
      differ by 5.5-8.2%. Phylogenetic analysis showed that Andes virus along with ESQ
      H-1/96 and CH H-1/96 form a distinct lineage within the clade containing Bayou
      and Black Creek Canal viruses. It also showed that Andes virus branch of trees
      derived from comparisons of S or M sequences differed. It is concluded that Andes
      virus variants causing HPS circulate east and west of the Andes mountains.

PMID- 9255938
TI  - EBV binds to lymphocytes of transgenic mice that express the human CR2 gene.
AB  - Epstein Barr virus (EBV) is unable to bind to or infect normal mouse lymphocytes.
      A construct containing the human complement receptor type 2 (CR2) gene, the
      receptor for EBV, was placed under the control of the IgH/c-fos enhancer/promoter
      and microinjected into single cell embryos. A total of five transgenic mouse
      lines were established and four expressed hCR2 mRNA. Flow cytometry and
      immunostaining revealed that approximately 15-30% of the lymphocytes from the
      thymus, spleen and lymph nodes expressed hCR2 protein on their surface and bound
      EBV. Despite this binding, less than 1% of the cells showed evidence that the
      virus was internalized or replicated. Transgenic mouse lymphocytes, expressing
      hCR2, could not be immortalized with EBV. It is concluded that the simple
      expression of hCR2 receptor on mouse lymphocytes is not sufficient for efficient
      infection.

PMID- 9255939
TI  - Comparative analyses of the latency-associated transcript promoters from herpes
      simplex virus type 1 strains H129, +GC and KOS-63.
AB  - We have analyzed the activity of a specific portion of the latency-associated
      transcript (LAT) promoter of three strains of herpes simplex virus type 1 (HSV-1)
      in neuronal and non-neuronal cell types. Restriction fragments containing the LAT
      promoter sequences and the 5'-end of the LATs were isolated from HSV-1 strains
      H129, +GC and KOS-63, sequenced and cloned into a chloramphenicol transferase
      (CAT) plasmid vector. These vectors were separately assayed for CAT production in
      human (SknSH) and mouse (C-1300) neuroblastoma cell lines and a human continuous
      cell line (HeLa). Strain KOS-63 contained a C to T base substitution within the
      LAT promoter binding factor element upstream of the cAMP response element binding
      sequence. In replicate experiments, in which the construct DNA was used for
      transfection, the CAT constructs from strains H129 and +GC functioned equally
      well in all three cell lines. In contrast, the strain KOS-63 CAT construct
      functioned significantly better in HeLa cells than in neuroblastoma cell lines
      and better than the identical CAT constructs from strains H129 and +GC. In
      addition, the construct from strain KOS-63 functioned less well in the human
      neuroblastoma cell line than in HeLa or C-1300 neuroblastoma cells. When LAT
      expression was examined directly in vivo by in situ hybridization, strain KOS-63
      produced slightly less LAT RNA than strain H129 within trigeminal ganglionic
      neurons of latently infected rabbits. However, utilizing competitive gel-shift
      assays, DNA fragments containing the LAT promoter binding element from all three
      strains bound equivalent amounts of HeLa cell nuclear proteins. Together, these
      results suggest that the activity expressed by the strain KOS-63 LAT promoter in
      vivo and in vitro may relate to positive or negative effects of DNA binding
      proteins on LAT transcription, and that these effects are cell-type dependent.

PMID- 9255940
TI  - Structural features of the metal binding site and dynamics of gallium
      putidaredoxin, a diamagnetic derivative of a Cys4Fe2S2 ferredoxin.
AB  - The first reconstitution of an Fe2S2 ferredoxin with a diamagnetic prosthetic
      group was recently described [Kazanis et al. (1995) J. Am. Chem. Soc., 117, 6625
      6626]. The replacement of the iron-sulfur cluster of the bacterial ferredoxin
      putidaredoxin (Pdx) by gallium (Ga3+) renders the protein diamagnetic and permits
      the use of high-resolution NMR methods to identify resonances near the metal
      binding site. We now describe structural features of the metal binding site that
      are not observable by standard NMR methods in native Pdx due to paramagnetic line
      broadening. These results provide the first example of high-resolution NMR
      derived structural data concerning the metal binding domain of an Fe2S2
      ferredoxin, and the first structural information of any sort for the metal
      binding site of a ferredoxin from this class, which includes adrenodoxin,
      placental ferredoxin and terpredoxin. Assignments were obtained by applying
      multidimensional NMR methods to a series of selectively and nonselectively 15N-
      and 13C/15N-labeled GaPdx samples. For most experiments, a mutant of Pdx was used
      in which a nonligating Cys85 is replaced by serine. All of the major structural
      features that were identified in native Pdx are conserved in GaPdx. The overall
      protein dynamics is considerably faster in GaPdx than in the native protein, as
      reflected by amide proton exchange rates. The C-terminal residue, Trp106, also
      exhibits considerable mobility, as indicated by 15N[1H] NOE and 15N T1 values of
      the C-terminal residue of the protein.

PMID- 9255942
TI  - Temperature dependence of 1H chemical shifts in proteins.
AB  - Temperature coefficients have been measured by 2D NMR methods for the amide and C
      alpha H proton chemical shifts in two globular proteins, bovine pancreatic
      trypsin inhibitor and hen egg-white lysozyme. The temperature-dependent changes
      in chemical shift are generally linear up to about 15 degrees below the global
      denaturation temperature, and the derived coefficients span a range of roughly 
      16 to +2 ppb/K for amide protons and -4 to +3 ppb/K for C alpha H. The
      temperature coefficients can be rationalized by the assumption that heating
      causes increases in thermal motion in the protein. Precise calculations of
      temperature coefficients derived from protein coordinates are not possible, since
      chemical shifts are sensitive to small changes in atomic coordinates. Amide
      temperature coefficients correlate well with the location of hydrogen bonds as
      determined by crystallography. It is concluded that a combined use of both
      temperature coefficients and exchange rates produces a far more reliable
      indicator of hydrogen bonding than either alone. If an amide proton exchanges
      slowly and has a temperature coefficient more positive than -4.5 ppb/K, it is
      hydrogen bonded, while if it exchanges rapidly and has a temperature coefficient
      more negative than -4.5 ppb/K, it is not hydrogen bonded. The previously observed
      unreliability of temperature coefficients as measures of hydrogen bonding in
      peptides may arise from losses of peptide secondary structure on heating.

PMID- 9255941
TI  - 1H and 15N NMR assignment and solution structure of the SH3 domain of spectrin:
      comparison of unrefined and refined structure sets with the crystal structure.
AB  - The assignment of the 1H and 15N nuclear magnetic resonance spectra of the Src
      homology region 3 domain of chicken brain alpha-spectrin has been obtained. A set
      of solution structures has been determined from distance and dihedral angle
      restraints, which provide a reasonable representation of the protein structure in
      solution, as evaluated by a principal component analysis of the global pairwise
      root-mean-square deviation (rmsd) in a large set of structures consisting of the
      refined and unrefined solution structures and the crystal structure. The solution
      structure is well defined, with a lower degree of convergence between the
      structures in the loop regions than in the secondary structure elements. The
      average pairwise rmsd between the 15 refined solution structures is 0.71 +/- 0.13
      A for the backbone atoms and 1.43 +/- 0.14 A for all heavy atoms. The solution
      structure is basically the same as the crystal structure. The average rmsd
      between the 15 refined solution structures and the crystal structure is 0.76 A
      for the backbone atoms and 1.45 +/- 0.09 A for all heavy atoms. There are,
      however, small differences probably caused by intermolecular contacts in the
      crystal structure.

PMID- 9255943
TI  - The effect of ring currents on carbon chemical shifts in cytochromes.
AB  - Calculations suggest that some carbon chemical shifts in proteins should have
      large ring current shifts (> 1 ppm). We present 13C, 15N and 1H assignments for
      cytochrome C2 from Rhodospirillum rubrum, compare these with shifts for other
      cytochromes c, and show that the calculated ring current shifts are similar to
      experimentally observed shifts, but that there remain substantial conformation
      dependent shifts of side-chain carbons. Ring current shifts as large as 6 ppm are
      observed. We show that the ring current effects do not seriously affect the
      Chemical Shift Index method for delineating secondary structure, but may have an
      impact on more precise methods for generating structural constraints.

PMID- 9255944
TI  - Hydrogen-deuterium exchange studies of the rat thyroid transcription factor 1
      homeodomain.
AB  - The 1H NMR solution structure of the rat thyroid transcription factor 1
      homeodomain (TTF-1 HD) showed that the molecule folds like classical
      homeodomains. The C-terminal extension of helix III (fragment 51-59) appeared to
      adopt a helical geometry, albeit not as rigid as the preceding portion, but the
      hydrogen-deuterium exchange of backbone amides and the NOE data provided evidence
      of a discontinuity between the two moieties of helix III at the highly conserved
      fragment Asn51-His52-Arg53. Analysis of quantitative measurements of isotope
      exchange rates allows one to recognize the general occurrence, in that region of
      HD motifs, of opposite effects to helix III stability. Asparagine, histidine and
      arginine residues occur most frequently at the beginning and end of protein
      helices. In TTF-1 HD a local fluctuation is observed in the fragment 51-53 which
      either kinks or tightens the alpha-helix. A search through the protein structure
      database reveals that the three most common variants of HD fragments 51-53 are
      often involved in helices and, frequently, in helix initiation or termination.
      For homeodomains in general, the nature of the fragment 51-53 may be related to
      the conformational dynamics of their DNA-recognition helix (helix III). Besides
      the specific results on fragment 51-53, the complete isotope exchange analysis of
      TTF-1 HD data shows that the partially solvent-exposed recognition helix is
      stabilized by hydrophobic interactions, like most of the structured regions of
      the molecule. Hydrophobic stabilization of the contacting regions meets the
      requirements of a DNA-interaction mechanism which, as shown with other DNA
      protein complexes, should entail negative heat capacity variations due to changes
      in solvent exposure of the nonpolar protein surface.

PMID- 9255945
TI  - Pulse schemes for the measurement of 3JC'C gamma and 3JNC gamma scalar couplings
      in 15N,13C uniformly labeled proteins.
AB  - Pulse sequences are presented for the measurement of 3JC'C gamma and 3JNC gamma
      scalar couplings for all C gamma containing residues in 15N,13C uniformly labeled
      proteins. The methods described are based on quantitative J correlation
      spectroscopy pioneered by Bax and co-workers [Bax et. al. (1994) Methods
      Enzymol., 239, 79-105]. The combination of 3JC'C gamma and 3JNC gamma scalar
      coupling constants allows the assignment of discrete rotameric states about the
      chi 1 torsion angle in cases where such states exist or, alternatively,
      facilitates the establishment of noncanonical chi 1 conformations or the presence
      of rotameric averaging. The methods are applied to a 1.5 mM sample of
      staphylococcal nuclease.

PMID- 9255946
TI  - Application of homonuclear 3D NMR experiments and 1D analogs to study the
      conformation of sialyl Lewis(x) bound to E-selectin.
AB  - The conformation of the sialyl Lewis(x) tetrasaccharide bound to E-selectin was
      previously determined from transfer NOE (trNOE) experiments in conjunction with a
      distance-geometry analysis. However, the orientation of the tetrasaccharide
      ligand in the binding site of E-selectin is still unknown. It can be predicted
      that the accurate quantitative analysis of all trNOEs, including those
      originating from spin diffusion, is one key to analyze the orientation of sialyl
      Lewis(x) in the binding pocket of E-selectin. Therefore, we applied homonuclear
      3D NMR experiments and 1D analogs to obtain trNOEs that could not unambiguously
      be assigned from previous 2D trNOESY spectra, due to severe resonance-signal
      overlap. A 3D TOCSY-trNOESY experiment, a 1D TOCSY-trNOESY experiment, and a 1D
      trNOESY-TOCSY experiment of the sialyl Lewis(x)/E-selectin complex furnished new
      interglycosidic trNOEs and provided additional information for the interpretation
      of trNOEs that have been described before. A 2D trROESY spectrum of the sialyl
      Lewis(x)/E-selectin complex allowed one to identify the amount of spin-diffusion
      contributions to trNOEs. Finally, an unambiguous assignment of all trNOEs, and an
      analysis of spin-diffusion pathways, was obtained, creating a basis for a
      quantitative analysis of trNOEs in the sialyl Lewis(x)/E-selectin complex.

PMID- 9255947
TI  - Improved labeling strategy for 13C relaxation measurements of methyl groups in
      proteins.
AB  - Selective incorporation of 13C into the methyl groups of protein side chains is
      described as a means for simplifying the measurement and interpretation of 13C
      relaxation parameters. High incorporation (> 90%) is accomplished by using
      pyruvate (3-13C, 99%) as the sole carbon source in the growth media for protein
      overexpression in E. coli. This improved labeling scheme increases the
      sensitivity of the relaxation experiments by approximately fivefold when compared
      to randomly fractionally 13C-labeled protein, allowing high-quality measurements
      on relatively dilute (< 1 mM) protein samples at a relatively low cost.

PMID- 9255948
TI  - Sequence-specific 1H, 13C and 15N assignment of the TMP-resistant dihydrofolate
      reductase mutant DHFR(F98Y) in the ternary complex with TMP and NADPH.

PMID- 9255949
TI  - Perireception in olfaction: molecular mass sieving by aesthetasc sensillar
      cuticle determines odorant access to receptor sites in the Caribbean spiny
      lobster Panulirus argus.
AB  - The responsiveness of chemoreceptor neurons depends on a combination of
      perireceptor and receptor events. Olfactory neurons of crustaceans are packaged
      into distinctive cuticular sensilla called aesthetascs. The cuticle of
      aesthetascs is thin and permeable, even though it does not contain any obvious
      surface pores or pore tubules. This suggests that this 'spongy' aesthetasc
      cuticle may act as a molecular sieve that restricts large odorant molecules from
      entering the sensilla and binding to the olfactory neurons. We examined whether
      this is so for the aesthetasc cuticle of the Caribbean spiny lobster Panulirus
      argus. We used a chromatographic column packed with aesthetasc cuticle and
      connected to a flow-through ultraviolet spectrophotometer to measure the elution
      times of ultraviolet-absorbent molecular mass markers between 165 and 2 x 10(6)
      Da. Molecules larger than approximately 8.5 kDa had similar elution times,
      indicating that they did not penetrate the cuticle. Molecules smaller than 8.5
      kDa had longer elution times that were directly and inversely proportional to
      their molecular mass. These results suggest that aesthetasc cuticle excludes
      molecules larger than 8.5 kDa from having access to the olfactory receptor
      neurons. We conclude that the molecular sieving capacity of the aesthetasc
      cuticle of P. argus is a perireceptor mechanism that is a critical determinant of
      the types of molecules capable of stimulating its olfactory receptors.

PMID- 9255950
TI  - Heart rates of northern elephant seals diving at sea and resting on the beach.
AB  - Heart rates of northern elephant seals diving at sea and during apnoea on land
      were monitored to test whether a cardiac response to submergence is an important
      factor in their ability to make repetitive, long-duration dives. Seven juvenile
      northern elephant seals were captured at Ano Nuevo, CA, instrumented and
      translocated to release sites around Monterey Bay. Heart rate and dive depth were
      recorded using custom-designed data loggers and analogue tape monitors during the
      seals' return to Ano Nuevo. Heart rates during apnoea and eupnoea were recorded
      from four of the seals after they hauled out on the beach. Diving patterns were
      very similar to those of naturally migrating juveniles. The heart rate response
      to apnoea at sea and on land was a prompt bradycardia, but only at sea was there
      an anticipatory tachycardia before breathing commenced. Heart rate at sea
      declined by 64% from the surface rate of 107 +/- 3 beats min-1 (mean +/- S.D.),
      while heart rate on land declined by 31% from the eupnoeic rate of 65 +/- 8 beats
      min-1. Diving heart rate was inversely related to dive duration in a non-linear
      fashion best described by a continuous, curvilinear model, while heart rate
      during apnoea on land was independent of the duration of apnoea. Occasionally,
      instantaneous heart rate fell as low as 3 beats min-1 during diving. Although
      bradycardia occurs in response to apnoea both at sea and on land, only at sea is
      heart rate apparently regulated to minimise eupnoeic time and to ration oxygen
      stores to ensure adequate supplies for the heart and brain not only as the dive
      progresses normally but also when a dive is abnormally extended.

PMID- 9255951
TI  - Do metabolic responses to solar radiation scale directly with intensity of
      irradiance?
AB  - Endotherms exposed to air temperatures below thermal neutrality reduce their
      metabolic heat production when exposed to sunlight. The physiological effects of
      this additional source of heat gain from the environment usually are assumed to
      be proportional to the intensity of irradiance if other factors are held
      constant. We test this assumption by measuring changes in metabolic heat
      production produced by exposing a small mammal, the Siberian hamster (Phodopus
      sungorus) to four intensities of simulated solar radiation (0 W m-2, 317 W m-2,
      634 W m-2 and 950 W m-2). In the absence of solar radiation, metabolic heat
      production is inversely correlated with air temperature over the measured range
      of 3-27 degrees C. The respiratory quotient varies significantly with ambient
      temperature, indicating that the catabolic substrate and the thermal equivalent
      of oxygen consumed or carbon dioxide produced also vary with temperature. The
      depression of metabolic heat production resulting from exposure to simulated
      solar radiation is not simply a multiple of the intensity of irradiance. Rather,
      metabolic responses to higher levels of irradiance are blunted by 14-29% compared
      with those expected on the basis of the response to less intense irradiance.
      Because changes in irradiance levels do not have simple linear effects upon the
      animal's metabolic heat production, even in a simplified situation, significant
      errors may accumulate in biophysical analyses in which an animal's responses to a
      restricted set of radiative conditions are measured and the results are
      extrapolated to a wider range observed in nature.

PMID- 9255953
TI  - Parental distress and children's problems among single-parent families in China.
AB  - The coercion model explains reciprocal relationships between parents' and
      children's adjustment problems, with the mediation of parenting behavior and
      social relationships. A survey of 301 single parents in Guangzhou, China, was
      performed to test such a model with reference to parental distress, perceived
      behavioral problems and anxiety of the eldest child, acceptance of the child, and
      experienced social pressure and social support. Structural equation modeling
      demonstrated a good fit of the coercion model as a theoretically based and
      simplified representation of the relationships, supporting the hypotheses that
      (a) the parent's acceptance helps prevent the child's behavioral problems, (b)
      the child's behavioral problems and anxiety contribute to the parent's distress,
      (c) the child's behavioral problems and anxiety invite social pressure on the
      parent, (d) social pressure on the parent aggravates and social support for the
      parent attenuates the parent's distress, (e) social pressure on and social
      support for the parent facilitate the parent's acceptance of his or her child.
      However, the effect of parental distress on acceptance of the child was not
      significant.

PMID- 9255954
TI  - A re-examination of the relationship between shyness, attributional style, and
      depression.
AB  - Alfano, Joiner, and Perry (1994) used analysis of variance and analysis of
      covariance in a sample of college students to demonstrate that attributional
      style mediates between shyness and depression, as opposed to depression mediating
      between shyness and attributional style. They suggested, however, the
      hypothetical possibility of a third model, in which negative attributional style,
      rather than shyness, is the independent variable, and shyness serves as a
      mediator between attributional style and depression. In the current study, this
      alternative model was tested by using LISREL to reanalyze the Alfano et al. data.
      Results showed that this third model, with shyness as the mediating variable, fit
      the model quite poorly, in contrast to the preferred model of Alfano et al.,
      which fit quite well. However, variants of this model, in which shyness
      functionally precedes both attributional style and depression, fit the data
      better. The substantive implications of this model for counseling practice and
      the methodological cautions about interpreting cross-sectional data for temporal
      sequences are discussed.

PMID- 9255955
TI  - Intuitive parenting and infant behavior: concepts, implications, and empirical
      validation.
AB  - On the basis of the concept of intuitive parenting, the expectation was
      formulated that a mother's tendency to reflect on her parenting behavior would
      impede intuitive responses to infant signals. Also, a high quality of parental
      interactional behavior was expected to be related to fewer problems of the child
      (e.g., less crying, fewer reported difficulties, fewer health problems). An
      observational study with 62 mothers and their 3-month-old children confirmed the
      assumption that reflection about parenting during face-to-face interactions
      interferes with intuitive behavior. However, in contrast to initial expectations,
      a high quality of parenting was related, not to fewer, but rather to more health
      and behavioral problems of the child. Conceptual differentiations of the initial
      assumptions are discussed.

PMID- 9255956
TI  - Cross-cultural comparison of need importance and need satisfaction during
      adolescence: Turkey and the United States.
AB  - Turkish and U.S. adolescents' views concerning the importance of different needs
      and instrumentality of relationships with mothers, fathers, siblings, and same
      sex friends for need satisfaction were examined and compared. Questionnaires
      covered needs related to crucial issues of adolescence, namely, relatedness and
      autonomy/individuation. Participants were 12- to 17-year-old boys and girls from
      intact families. Cross-cultural differences in ascribed importance of needs
      related to some aspects of relatedness and autonomy/individuation emerged. Cross
      cultural similarities in ascribed importance of needs related to feelings of
      basic acceptance and need for self-understanding/development also emerged.
      Turkish adolescents perceived mothers as more instrumental for need satisfaction
      than did U.S. adolescents. Gender differences in importance ascribed to different
      needs also emerged. Cross-cultural differences were consistent with differences
      in predominant values and model family dynamics of the respective countries.

PMID- 9255957
TI  - The association between receptive nonverbal processing abilities and
      internalizing/externalizing problems in girls and boys.
AB  - Social adjustment correlates of individual differences in receptive nonverbal
      processing abilities in boys and girls were investigated. Participants were 26
      boys and 13 girls, mean age 12.04 years, who were in a custodial care institution
      for the treatment of a wide range of psychological difficulties. They completed
      the Diagnostic Analysis of Nonverbal Accuracy (DANVA; Nowicki & Duke, 1994), a
      standardized test of receptive nonverbal processing abilities. Trained raters
      used institutional records to assess the number and type of problems
      (internalizing or externalizing) experienced by each child. Teachers completed a
      social adjustment scale for each child. Girls' scores on the DANVA tests of child
      facial expression, child and adult facial expression combined, posture, and total
      DANVA accuracy as well as teacher ratings of social adjustment were significantly
      related to the number of externalizing problems they had. No other relations were
      significant. The findings suggest that receptive nonverbal processing skills may
      be more important for social adjustment for girls than for boys.

PMID- 9255958
TI  - Parental conflict and self-esteem: the rest of the story.
AB  - Previous research has supported the hypothesis that high levels of marital
      conflict are related to lower self-esteem in children. In this study, 122 young
      adults completed the Rosenberg Self-Esteem Questionnaire and the Student
      Interparental Conflict Scale, as well as the Parental Nurturance Scale and the
      Parental Authority Questionnaire. One parent of each young adult completed the
      Parent Interparental Conflict Scale, the O'Leary-Porter Overt Hostility Scale,
      and a modified Parental Authority Questionnaire. Perceived interparental conflict
      and parental style discrepancies in nurturance and in authoritarianism were
      significantly and negatively related to self-esteem, but the best predictors of
      self-esteem were the parental styles themselves. Warm, nurturant parents were
      more likely to have high self-esteem children and demonstrated less conflict in
      marital partnerships. Correlations between marital conflict and self-esteem may
      reflect parental characteristics.

PMID- 9255959
TI  - A study and meta-analysis of lay attributions of cures for overcoming specific
      psychological problems.
AB  - Lay beliefs about the importance of 24 different contributors to overcoming 4
      disorders that constitute primarily cognitive deficits were studied. A meta
      analysis of previous programmatic studies in the area was performed so that 22
      different psychological problems could be compared. In the present study, 107
      participants completed a questionnaire indicating how effective 24 factors were
      in overcoming 4 specific problems: dyslexia, fear of flying, amnesia, and
      learning difficulties. Factor analysis revealed almost identical clusters (inner
      control, social consequences, understanding, receiving help, and fate) for each
      problem. The perceived relevance of those factors differed significantly between
      problems. Some individual difference factors (sex and religion) were found to
      predict certain factor attributions for specific disorders. A meta-analysis of
      the 5 studies in this series yielded a 6-factor structure comparable to those of
      the individual studies and provided results indicating the benefits and
      limitations of this kind of investigation. The clinical relevance of studying
      attributions for cure is considered.

PMID- 9255960
TI  - Student gender and teaching methods as sources of variability in children's
      computational arithmetic performance.
AB  - An experimental study of the effects of a didactic teaching approach and a
      constructivist teaching approach on 3rd- and 5th-grade boys' and girls'
      performance on arithmetic computation problems was conducted. Two groups of
      children, matched on the basis of initial computation performance as well as
      grade and gender, were taught how to solve arithmetic problems using one of these
      two instructional approaches. Analysis of subsequent computation test performance
      revealed that 5th graders scored higher than 3rd graders, and there was a
      significant interaction between gender and instruction group. After instruction,
      girls in the didactic group outperformed boys in both instruction groups and
      girls who had been taught using constructivist approaches. Gender differences in
      computation performance can appear relatively early, by 3rd grade, if didactic
      instruction strategies are used to teach computational rules. The pattern of
      gender differences suggests that didactic teaching does not handicap boys.
      Rather, it appears that didactic instruction enhances computational performance
      in girls.

PMID- 9255962
TI  - The relation of nonverbal processing ability of faces and voices and children's
      feelings of depression and competence.
AB  - The relation between nonverbal processing ability and feelings of depression and
      competence was evaluated in children between the ages of 7 and 11 years (N =
      142). They were administered tests to measure their receptive nonverbal ability
      and feelings of depression and competence. Hierarchical regression analyses
      revealed that nonverbal ability was related to feelings of competence in boys and
      girls, but to feelings of depression only in boys. It was concluded that specific
      nonverbal deficits are associated with generalized negative feelings in children.
      Implications for adjustment are discussed.

PMID- 9255961
TI  - Visual and semantic support for paired-associates recall in young and older
      adults.
AB  - A paired-associates task was used to investigate the degree to which young and
      older adults benefit from visual and semantic support for recall. Respondents
      were asked to recall pictorial or verbal items that were either semantically
      related or unrelated. As has been previously observed in spatial memory tasks,
      older adults benefited to a greater degree from pictorial materials than did
      young adults, but only for semantically related items. No such effect was
      observed for unrelated items. In a second experiment, the imposition of a speed
      requirement at retrieval eradicated the unequal recall facilitation effect for
      the older participants. The results of this study are consistent with Craik's
      (1986) environmental support theory and suggest a link between visuospatial loss
      and cognitive speed loss in the normal aging process.

PMID- 9255963
TI  - Preschool children's use of information about age and perceptual access to infer
      another person's knowledge.
AB  - Preschool children's use of information about age and perceptual experience to
      infer other people's knowledge was investigated. Because young children may view
      adults as omniscient, the hypothesis that 3-year-olds regard an observer's age
      and perceptual experience as equally important when inferring the observer's
      knowledge was tested. In Experiment 1, 3- and 4-year-olds were asked to judge
      which of 2 observers, 1 adult and 1 same-age child, knew the identity of a hidden
      object. On some trials, the adult looked at the hidden object; on other trials,
      the same-age peer looked at the hidden object. The children who were 3.5 years
      old relied on information about perceptual experience when judging knowledge.
      However, the younger 3-year-olds often chose the peer, even though the adult was
      knowledgeable. The children may have chosen the peer on the basis of familiarity;
      therefore, adult and child dolls were used in Experiment 2. Neither the 3-year
      olds nor the 4-year-olds attributed knowledge on the basis of age rather than
      perceptual experience.

PMID- 9255964
TI  - Remembering details in stories about childhood sexual abuse.

PMID- 9255965
TI  - Nuclear pore complex structure in birds.
AB  - The nuclear envelope consists of two parallel membranes enclosing an aqueous
      lumen. In places there are pores in both membranes at which the two membranes are
      joined. Within these pores reside the nuclear pore complexes. The current
      structural models of the nuclear pore complex have been derived from a number of
      studies using different electron microscopical techniques. Recently, using
      surface imaging techniques such as field emission in-lens scanning electron
      microscopy, novel structures have been identified, particularly at the periphery
      of the structure, most notably the nucleoplasmic basket. One limitation of the
      current models is that they are based almost entirely on nuclear envelopes
      isolated from amphibian oocytes and a pressing question is whether this structure
      is the same in other organisms and tissues. Here we have studied the structure of
      nuclear envelopes isolated from bird oocytes. We show that the overall structure
      is remarkably conserved. In particular, recently discovered peripheral structures
      appear very similar. We see variations in basket conformation but believe that
      this is related to the functional states of individual pore complexes.

PMID- 9255966
TI  - Fourier transform infrared spectral evidences for protein conformational changes
      in immature cataractous human lens capsules accelerated by myopia and/or systemic
      hypertension.
AB  - The possible changes in protein structures of the cataractous human lens capsules
      of the immature patients with myopia and/or systemic hypertension have been
      investigated using Fourier transform infrared (FT-IR) microspectroscopy. Second
      derivative and deconvolution methods have been applied to obtain the position of
      the overlapping components of the amide I band and assign them to different
      secondary structures. Changes in the protein secondary structure and composition
      of amide I band were estimated quantitatively from Fourier self-deconvolution and
      curve fitting algorithms. The results indicate that myopia and/or systemic
      hypertension were found to significantly modify the protein secondary structure
      of the cataractous human lens capsules to increase the beta-type structure and
      random coil and decrease the alpha-helix structure. Myopia-induced conformational
      change in triple helix structure was more pronounced. In conclusion, myopia
      and/or systemic hypertension seem to modify the conformation of the protein
      structures in cataractous human lens capsule to change ionic permeation through
      lens capsule to accelerate the cataract formation of senile patients.

PMID- 9255968
TI  - Random amplified polymorphic DNA (RAPD) analyses for discriminating genotypes of
      Microcystis cyanobacteria.
AB  - Random amplified polymorphic DNA (RAPD) analysis was used to discriminate
      genotypes in five species of Microcystis cyanobacteria. Strains of each group
      with the identical allozyme genotype (T. Kato et al., Algol. Stud., 1991, 129
      140; M. Watanabe, in "Toxic Microcystis," ed. by M.F. Watanabe et al., CRC Press,
      Tokyo, 1966, pp. 13-34) gave similar RAPD patterns characterizing the respective
      group. On the other hand, no similarities in RAPD patterns were observed among
      strains of which allozyme genotypes were different. A good accordance between the
      RAPD analysis and allozyme divergence indicated a high reliability of both
      methods for discrimination of the affiliated groups of Microcystis. Several
      amplified DNA fragments, which were expected to be markers for a particular taxon
      with identical allozyme genotype, were also observed on the RAPD patterns.
      Genetic homogeneities of M. novacekii, M. viridis, and M. wesenbergii were shown
      by RAPD analysis as well as the allozyme genotype. However, significant
      variations were observed in M. aeruginosa and M. ichthyoblabe in the levels of
      DNA and proteins (allozymes).

PMID- 9255969
TI  - Purification and calcium dependence of transglutaminases from sheep hair
      follicles.
AB  - To study the calcium sensitivity of sheep hair follicle transglutaminase, which
      was reportedly calcium-independent [H. W. Harding and G.E. Rogers, Biochemistry,
      11, 2858-2863 (1972)], the enzyme was purified from a homogenate of merino sheep
      hair follicles and its calcium dependence was examined. As a result of
      purification, two types of transglutaminases (DEAE-unabsorbed and absorbed
      transglutaminase, DU-TG and DA-TG, respectively) were obtained. The molecular
      mass of DU-TG was 77 and 82 kDa by SDS-PAGE and gel filtration, respectively,
      while that of DA-TG was 40 and 80 kDa. Each enzyme was obviously calcium
      dependent and contained (a) cysteine residue(s) in the active site, like other
      known mammalian transglutaminases. Maximum activation of DU-TG and DA-TG was
      observed at 1 and 0.1 mM CaCl2, respectively.

PMID- 9255967
TI  - Preparation of oligosaccharide units library and its utilization.
AB  - There is high current interest in developing synthetic routes to oligosaccharides
      involved in glycoconjugates. Significant attention has been focused on the
      application of glycosidase-catalyzed transglycosylation for practical synthesis
      of oligosaccharides. The enzymatic synthesis has become more practical by the use
      of several glycosidases available in sufficient quantities. This review describes
      convenient syntheses of di- and trisaccharide units, which are related to
      molecular recognition, by using regioselective transgalactosylation, trans-N
      acetylglucosaminylation, transfucosylation, and transmannosylation. The
      regioselectivity could be controlled to some extent by using the following
      techniques: (1) varying enzymes, (2) organic co-solvent system, (3) the
      configuration of the existing glycosidic linkage of the acceptor and (4)
      inclusion complex of acceptor glycoside with cyclodextrin. Furthermore,
      glycopolymers carrying a series of disaccharides containing beta-D-galactosyl
      residues were synthesized and used as a model in oligosaccharide-lectin
      interaction analysis. These water-soluble glycopolymers were shown to be useful
      as probes of carbohydrate recognition.

PMID- 9255970
TI  - A catalytic amino acid and primary structure of active site in Aspergillus niger
      alpha-glucosidase.
AB  - The catalytic amino acid residue of Aspergillus niger alpha-glucosidase (ANGase)
      was identified by modification with conduritol B epoxide (CBE), a mechanism-based
      irreversible inactivator. The inactivation by CBE followed pseudo-first order
      kinetics. The interaction of CBE and ANGase conformed to a model with a
      reversible enzyme-inhibitor complex formed before covalent inactivation. A
      competitive inhibitor, Tris, decreased the inactivation rate. The incorporation
      of one mole of CBE per mole of ANGase was completely abolished the enzyme
      activity. A dissociated carboxyl group (-COO-) in the active site was suggested
      to attack the C-1 of CBE. ANGase was composed of two subunits (P1 and P2), of
      which P2 was modified by CBE. The labelled residue was included in a peptide
      (LY3) that was obtained from Lys-C protease digestion of CBE-bound P2. The
      sequence analysis of CBE-labelled LY3 showed that an Asp was the modified
      residue, that is, one of the catalytic amino acid residues of ANGase. The primary
      structure of LY3 was determined by analyzing the sequence of peptide fragments
      prepared by several proteases.

PMID- 9255972
TI  - Purification and properties of an aminopeptidase from a protamine-degrading
      marine bacterium.
AB  - A protamine-degrading marine bacterium was isolated from marine soil and
      identified as Aeromonas salmonicida subsp. based on its taxonomical
      characteristics. An alanine-specific aminopeptidase, called aminopeptidase K,
      from an extract of the strain was purified and characterized. The aminopeptidase
      K was purified about 80-fold by fractionation with ammonium sulfate and column
      chromatography on QA-52 cellulose, Phenyl Superose and Superose 12. The purified
      enzyme is composed of 6 subunits of 86 kDa with a molecular mass of 520 kDa
      according to gel filtration and SDS-PAGE. The N-terminal sequence of the enzyme
      was H.Gly-Gln-Gln-Pro-Gln-Ile-Lys-Try-Tyr-His-Asp-Tyr-Asp-Ala-Pro-Asp-Tyr-Ty r-
      Ile-Thr-. It is inhibited by monoiodoacetate, N-ethylmaleimide, and puromycin.
      The Michaelis constant (K(m)) and the maximal rate of hydrolysis (Vmax) were,
      respectively, 0.28 mM and 49.4 mumol/min/mg for the L-Ala-beta-naphthylamide
      substrate. The optimum pH and optimum temperature were 6.5 and 45 degrees C,
      respectively. The purified enzyme was highly specific to L-Ala-beta
      naphthylamide.

PMID- 9255971
TI  - Inhibitory effects of persimmon (Diospyros kaki) extract and related polyphenol
      compounds on growth of human lymphoid leukemia cells.
AB  - We have investigated the effects of persimmon (Diospyros kaki) extract (PS) and
      related polyphenol compounds such as catechin (C), epicatechin (EC),
      epicatechingallate (ECG), epigallocatechin (EGC), and epigallocatechingallate
      (EGCG) on the growth of human lymphoid leukemia Molt 4B cells. We found that PS,
      ECG, EGC, and EGCG strongly inhibited the growth of the cells in a dose-dependent
      manner, while C and EC inhibited the growth of the cells only moderately.
      Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis,
      was inhibited by 10-20% by these polyphenol compounds. The morphology of the Molt
      4B cells indicated severe damage 3 days after treatment with PS, ECG, EGC, and
      EGCG. Irregular shape of the cells and DNA fragmentation were observed in PS,
      ECG, EGC, or EGCG-treated cells. These results suggest that PS, ECG, EGC, and
      EGCG induce apoptosis (programmed cell death) of Molt 4B cells.

PMID- 9255973
TI  - Relationship between the glutamate production and the activity of 2-oxoglutarate
      dehydrogenase in Brevibacterium lactofermentum.
AB  - Enzyme activities of 2-oxoglutarate dehydrogenase complex and glutamate
      dehydrogenase of wild type Brevibacterium lactofermentum, one of the typical
      glutamate-producing coryneform bacteria, were investigated by using cells
      cultured under glutamate-productive and glutamate-non-productive conditions.
      Significant reduction of the former enzyme activity was observed in the cells
      under the several glutamate-productive conditions, namely, in the cells cultured
      in media containing a) limited concentrations of biotin, b) sub-lethal amounts of
      penicillin, and c) sub-optimal amounts of a surface-active agent, as compared
      with those under the non-productive conditions. The activity of the latter enzyme
      was essentially unchanged in every condition. The relationship between glutamate
      production and the enzyme activities as well as permeability of glutamate through
      cell membrane was discussed from the results obtained.

PMID- 9255974
TI  - Galactosyl transfer onto p-nitrophenyl beta-D-glucoside using beta-D
      galactosidase from Bacillus circulans.
AB  - beta-D-Gal-(1-->4)-beta-D-Glc-OC6H4NO2-p and its isomers (beta-D-Gal-(1-->3)-beta
      D-Glc-OC6H4NO2-p and beta-D-Gal-(1-->6)-beta-D-Glc-OC6H4NO2-p) were synthesized
      from lactose and beta-D-Glc-OC6H4NO2-p, using transglycosylation by the beta-D
      galactosidase from Bacillus circulans. This reaction was efficient enough for us
      to do a one-pot preparation of galactosyl-glucoside from lactose. The order of
      the production of the transfer products was (1-->4) > > (1-->3) > (1-->6) in the
      initial stage of the reaction, and the same relationship was observed for the
      hydrolytic rate toward the three galactosyl-glucosides. The production of (1-->4)
      and (1-->3)-linkages greatly decreased during the subsequent reaction and much
      more of the (1-->6)- than of the (1-->4)- and (1-->3)-transfer products was found
      in the later stage of the reaction.

PMID- 9255975
TI  - The effects of substituents introduced into 9-aminoacridine on frameshift
      mutagenicity and DNA binding affinity.
AB  - Some derivatives of 9-aminoacridine (1) were synthesized, and their frameshift
      mutagenicity and DNA binding affinity were studied. The introduction of a methyl
      group into the acridine ring of 1 reduced the mutagenic activity and the
      intercalative DNA binding affinity, while the introduction of chlorine increased
      them. Halogenated derivatives of 1 showed higher toxicity against Salmonella
      typhimurium TA1537.

PMID- 9255976
TI  - Further studies on thermal denaturation of pyruvate dehydrogenase complex from
      Bacillus stearothermophilus.
AB  - Thermally induced changes in pyruvate dehydrogenase complex (PDC) from B.
      stearothermophilus were examined mainly at temperatures from 60 degrees to 70
      degrees C. Accompanied by inactivation of pyruvate decarboxylase, light
      scattering decreased, and ANS fluorescence increased. These changes including the
      inactivation were approximately first-order reactions, and the values of rate
      constants were greatly dependent on temperature. Chromatographic studies showed
      that any polypeptides were in associated forms and that final products were
      aggregates (> 230S) and an assembly (48S) smaller than PDC. The aggregates and
      assembly were rich in decarboxylase and lipoate acetyltransferase, respectively.
      It was suggested that, during the thermal denaturation, a decarboxylase was
      dissociated from PDC and immediately involved in aggregates.

PMID- 9255977
TI  - Inactivation of food microorganisms by high-pressure carbon dioxide treatment
      with or without explosive decompression.
AB  - In order to elucidate the sterilization mechanism underlying the explosive
      decompression system, baker's yeast was pressurized with CO2, N2O, N2, or Ar gas
      at 40 atm and 40 degrees C for 4h, and then explosively discharged. The survival
      ratio was markedly decreased only by the treatments with CO2 and N2O, which are
      relatively soluble gases in water, suggesting that the microorganisms' death may
      be highly correlated with gas absorption by the cells. Lower decompression rates
      to atmospheric pressure, however, led to neither any lower reduction of remaining
      cells nor any smaller release of total cellular proteins. Furthermore, operating
      with a longer treatment time and smaller number of repetitions was usually more
      lethal than with a shorter time and more frequent repetition. From these results,
      most of the yeast cells appear to have been sterilized during the pressurization
      process. The spore cells of B. megaterium are considered to have been killed in a
      somewhat different manner, because of their distinct sensitivity to the applied
      gases.

PMID- 9255978
TI  - Synthesis of glycosyl-trehaloses by cyclomaltodextrin glucanotransferase through
      the transglycosylation reaction.
AB  - Cyclomaltodextrin glucanotransferase from Bacillus stearothermophilus produced a
      series of glycosyl-trehaloses through the transglycosylation reaction with
      cyclomaltohexaose as the glycosyl donor and trehalose as its acceptor. After beta
      amylase treatment, five species of glycosyl-trehaloses were isolated by column
      chromatography. After chemical and enzymatic analyses, it was concluded that
      these oligosaccharides were alpha-maltosyl alpha-D-glucopyranoside, alpha
      maltotriosyl alpha-D-glucopyranoside, alpha-maltosyl alpha-maltoside, alpha
      maltotriosyl alpha-maltoside, and alpha-maltotriosyl alpha-maltotrioside. These
      were not hydrolyzed by salivary amylase, artificial gastric juice, or pancreatic
      amylase, however they were hydrolyzed by enzymes of the small intestine.

PMID- 9255979
TI  - Effects of medium-chain fatty acids and their acylglycerols on the transport of
      penicillin V across Caco-2 cell monolayers.
AB  - The transport-enhancing effects of medium-chain fatty acids (caproic, caprylic,
      and capric acids) and their acylglycerols (mono-, di-, and triacylglycerols) were
      investigated by using Caco-2 cell monolayers as a model of the human intestinal
      epithelium. Penicillin V was used as a model for a hydrophilic bioactive
      compound. Among the fatty acids and acylglycerols tested, 1,2-dicaproin,
      monocaprin, monocaprylin, and capric acid sodium salt effectively enhanced the
      transport rate, whereas other substances enhanced the rate only slightly or not
      at all. With each of these four substances, the rate of enhancement was
      proportional to the concentration at low concentrations, but leveled off at high
      concentrations. The transport-enhancing effects were well correlated with the
      reduction in surface tension and with a physico-chemical parameter, denoted by
      the surface energy-lowering coefficient, characterizing the surface activity of a
      substance.

PMID- 9255980
TI  - Enhancing effect of interleukin-4 on the secretion of interferon-gamma by alpha
      s1-casein-specific CD8+ T cells.
AB  - alpha s1-Casein-specific CD8+ T cell clones expressed the interleukin (IL)-4
      receptor, although they did not secrete detectable IL-4. We found that IL-4
      significantly enhanced the secretion of interferon (IFN)-gamma by these CD8+ T
      cell clones. IL-4 also enhanced the secretion of IFN-gamma induced by stimulating
      the immobilized anti-CD3 antibodies of polyclonal CD8+ T cells which had been
      isolated from lymph nodes and were stimulated in vitro with the immobilized anti
      CD3 antibody and IL-2. In addition, IL-4 added at the time of this first in vitro
      stimulation induced strong IFN-gamma productivity, as well as IL-4 and IL-10
      productivity, which were detectable upon restimulation of these cells. Results
      are discussed in relation to the inhibitory effects of IFN-gamma production on IL
      4-producing cells.

PMID- 9255981
TI  - Purification and characterization of glutamate decarboxylase from Lactobacillus
      brevis IFO 12005.
AB  - Glutamate decarboxylase (GAD) [EC 4.1.1.15] was purified from a cell-free extract
      of Lactobacillus brevis IFO 12005 by chromatographies on Sephadex G-100, DEAE
      Sepharose CL-6B, and Mono Q. About 9 mg of purified GAD was obtained from 90.2 g
      of wet cells. The purified preparation showed a single protein band on SDS-PAGE.
      The molecular weights of purified GAD by SDS-PAGE and gel filtration on Superdex
      200 were 60,000 and 120,000, respectively, indicating that GAD from L. brevis
      exists as a dimer. The N-terminal amino acid sequence of the purified GAD was NH2
      Met-Asn-Lys-Asn-Asp-Gln-Glu-Gln-Thr-. The optimum pH and temperature of GAD were
      at pH 4.2 and at 30 degrees C. The GAD activity was increased by the addition of
      sulfate ions in a dose-dependent manner. The order of effects was as follows:
      ammonium sulfate > sodium sulfate > magnesium sulfate, indicating that the
      increase of hydrophobic interaction between subunits causes the increase of GAD
      activity. The purified GAD reacted only with L-glutamic acid as a substrate and
      the K(m), kcat, and kcat/K(m) values were 9.3 mM, 6.5 S-1, and 7 x 10(2) M-1 S-1,
      respectively.

PMID- 9255982
TI  - Isolation and characterization of kar2-404 mutation in Saccharomyces cerevisiae.
AB  - We have devised a direct screening method to isolate mutations in the KAR2 gene,
      and have isolated a BiP/KAR2 mutant, kar2-404, from Saccharomyces cerevisiae as a
      small halo-forming mutant of secreted mouse alpha-amylase. The mutation site was
      identified as a point mutation at t1337 to c1337 resulting in the Ile-404Thr
      mutation of mature Kar2-404p, located at the most NH2-terminal first beta-sheet
      structure (beta 1) of the putative peptide-binding domain. This isoleucine is
      highly conserved in the Hsp70 family. By pulse-chase experiments, no obvious
      difference was detected in the intracellular secretion rate of MF alpha 1-prepro
      signal-mouse-alpha-amylase between the wild type and the kar2-404 mutant.
      However, only about half the amount of secreted heterologous protein, mouse alpha
      amylase, was detected in the mutant culture medium compared with wild type. A
      smaller amount of homologous protein, alpha-factor, was also detected and
      decreased faster in the mutant culture medium than in wild type. Kar2-404p was
      expressed about 3-fold more than wild type Kar2p, probably to cover its defective
      functions, and the turnover rates of Kar2p and Kar2-404p were about the same in
      vivo. The purified Kar2-404p was slightly more sensitive to chymotryptic
      digestion than Kar2p in vitro.

PMID- 9255983
TI  - Characteristics of Escherichia coli HB101 and Pseudomonas putida PpY101 harboring
      a recombinant plasmid with tandem insertion of the mercury resistance operon.
AB  - We constructed the plasmid pSUPmer2 by inserting tandem copies of the mercury
      resistance (mer) operon into a broad host range-vector, and introduced it into
      Escherichia coli HB101 and Pseudomonas putida PpY101 to increase their mercury
      resistance. Strains harboring plasmid pSUPmer2 had higher mercury resistance and
      mercuric reductase activity than those strains harboring the plasmid pSUPmer
      which had one copy of the mer operon. Mercury resistance of P. putida PpY101 was
      significantly increased by tandem insertion of the mer operon.

PMID- 9255984
TI  - Effect of chaotropic salt on the secondary structure of pigskin gelatin.
AB  - Pigskin gelatin was prepared and its molecular weight profile was examined by SDS
      PAGE. The major molecular weights of gelatin were 214 kDa, 135 kDa, and 122 kDa.
      The secondary structure of a gelatin solution in the presence of chaotropic salt
      was studied by using circular dichroism (CD). The CD study clearly showed that
      the chaotropic salt increased the ordered secondary structure of the gelatin
      solution due to the altered water structure.

PMID- 9255985
TI  - Increase of catalytic activity of alpha-chymotrypsin by metal salts for
      transesterification of an amino acid ester in ethanol.
AB  - alpha-Chymotrypsin-catalyzed transesterification of N-acetyl-L-tyrosine methyl
      ester in ethanol was markedly accelerated by addition of small amounts of
      divalent metal salts. The reaction rate dependent not only on the nature of metal
      ions but also on the nature of anionic counter ions. Calcium acetate was the most
      effective among the metal salts used. The reaction followed Michaelis-Menten
      kinetics, and it was found that the reaction increase is due to the increase in
      kcat.

PMID- 9255986
TI  - Effects of sex hormones on the metabolism of tryptophan to niacin and to
      serotonin in male rats.
AB  - It is known that deaths attributable to pellagra, which is considered to be a
      disease caused by the disturbance of tryptophan metabolism, have been
      approximately two-fold higher in women than in men. We investigated the effects
      of the administration of female and male sex hormones on the contents of
      tryptophan and such metabolites as serotonin, nicotinamide, N1
      methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone
      3-carboxamide, and on the conversion ratio of tryptophan to niacin in male rats.
      Feeding a diet containing estrone or testosterone had no effect on the
      concentrations of tryptophan and serotonin in the blood and brain, or on the
      concentration of 5-hydroxyindole-3-acetic acid in the brain. On the contrary,
      feeding a diet containing estrone caused to a decrease in the urinary excretion
      of nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and
      N1-methyl-4-pyridone-3-carboxamide, and of the conversion ratio of tryptophan to
      niacin when compared with the control rats. Feeding a diet containing
      testosterone had no effect on any parameter. We postulate from these findings
      that the cause of higher pellagra deaths in women than in men is attributable to
      the decrease in the formation of niacin from tryptophan, but not in the formation
      of serotonin by the female hormone. It seems likely that female sex hormones
      inhibit the synthesis of niacin from tryptophan, and that women, especially
      during pregnancy, will be more at risk to pellagra than are men.

PMID- 9255987
TI  - Accelerating effect of chitosan intake on urinary calcium excretion by rats.
AB  - The effect of chitosan on calcium (47Ca) metabolism was investigated in rats. The
      whole-body retention of 47Ca by rats fed on a 5% chitosan diet was significantly
      decreased when compared with that of rats fed on a cellulose diet, but showed no
      significant difference from that of rats fed on a fiber-free diet. Although there
      was no significant difference in the fecal excretion of 47Ca between the chitosan
      group and the cellulose or fiber-free group, the urinary excretion of 47Ca was
      significantly increased in the chitosan group when compared with the cellulose
      group. These results suggest that dietary chitosan would affect the calcium
      metabolism in animals.

PMID- 9255988
TI  - Construction of Escherichia coli-Bifidobacterium longum shuttle vector
      transforming B. longum 105-A and 108-A.
AB  - A shuttle vector, pBLES100, was constructed by cloning a Bifidobacterium longum
      plasmid and a gene encoding spectinomycin adenyltransferase AAD(9) from
      Enterococcus faecalis into the Escherichia coli vector pBR322. Stable
      transformants with this plasmid were obtained with an efficiency of 2.2 x 10(4)
      transformants/microgram DNA or 6.9 x 10(-5) transformants/cell/microgram DNA
      under the optimal conditions of 10.0 kV/cm, 200 omega, and 25 microF, using B.
      longum 105-A harvested at late log phase of growth.

PMID- 9255989
TI  - Thiamine increases expression of yeast gene.
AB  - We found that CPY production in Saccharomyces cerevisiae KS58-2D/pCY303 was
      increased by the addition of thiamine into the medium, while the addition of
      thiamine had no effect on cell growth. It became clear that the positive effect
      of thiamine was due to transcriptional increase, because the levels of CPYmRNA
      were increased according to the amount of thiamine added. Furthermore, it was
      suggested that thiamine generally increases the expression of yeast genes, since
      the expression of the luciferase gene that was artificially constructed was also
      increased to some extent by thiamine in S. cerevisiae.

PMID- 9255990
TI  - Toddler development.
AB  - The toddler years are ones of exciting and challenging changes in cognitive,
      affective, and physical growth. Physical growth is particularly remarkable for
      the child's increasing skills and ability to navigate the environment. Affective
      development is marked by the push for autonomy and independence and the highly
      visible nature of the child's temperament or behavioral style. The toddler also
      enters the wonderful years of imagination and pretend play. Perhaps most
      noteworthy is the child's dramatic increase in ability to communicate with others
      through speech and language, as evidence of the progression to symbolic thinking.
      The dynamic changes in children's development during the toddler years have
      important implications for child health supervision. Familiarity with toddler
      development will enable the pediatrician to monitor children's development
      effectively and to address common, stage-related behaviors with families during
      anticipatory guidance.

PMID- 9255991
TI  - Barbiturates.
AB  - Barbiturate use by adolescents has increased gradually in the past several years,
      but few adolescents use this class of drugs regularly. Instead, these sedatives
      are used most often to treat unpleasant effects of illicit stimulants, to reduce
      anxiety, and to get "high". Short-acting barbiturates such as pentobarbital and
      secobarbital are the preferred drugs of abuse. Barbiturates are dangerous drugs,
      with a narrow therapeutic index between the dose required for sedation and the
      dose that will cause coma and death. They are physiologically addicting if taken
      in high doses over 1 month or more, and the abstinence syndrome can be life
      threatening. Pregnant women who take barbiturates during the third trimester can
      give birth to addicted infants who undergo an extended withdrawal syndrome. It is
      important to educate adolescent patients about the hazards of sedative/hypnotic
      use, particularly frequent barbiturate use. As indicated in the findings from the
      1995 annual survey of United States high school seniors, many young people are
      not aware of the significant danger and toxicity of this class of drugs.

PMID- 9255992
TI  - Addressing behavior problems among school-aged children: traditional and
      controversial approaches.
AB  - Managing children's behaviors is primarily the responsibility of parents, but
      pediatricians can help parents be more effective managers, especially when the
      child involved is presenting a particular challenge. Such help can range from
      providing reading material and brief counseling to referring the family to mental
      health clinicians. First, the pediatrician must be able to identify and judge the
      severity of the problems to refer appropriately. Behavioral interventions,
      commonly based on the principles of behavior modification with an emphasis on
      improving the positive and reinforcing aspects of parent-child relationships, can
      be effective. In addition, pediatricians need to be aware of unconventional
      therapies in the categories of dietary and exercise interventions. They need to
      know what motivates parents to seek such therapies, how to judge the efficacy of
      these approaches, and how to help parents become better-informed consumers.

PMID- 9255993
TI  - Home care for children who have chronic conditions.

PMID- 9255994
TI  - Home care of children dependent on respiratory technology.

PMID- 9255995
TI  - Index of suspicion. Case 1. Acute rheumatic fever.

PMID- 9255996
TI  - Index of suspicion. Case 2. Hair tourniquet syndrome.

PMID- 9255997
TI  - Index of suspicion. Case 3. Antithrombin III deficiency.

PMID- 9255998
TI  - Quality framework for force plate testing.
AB  - Following work done in C.E.C. project AIM 2002 CAMARC II, a framework of the
      relevant standards for testing equipment used in laboratories analysing human
      movement is presented. In particular, gait analysis laboratories may provide a
      service for a clinical team considering treatment such as surgical intervention
      or provision of orthoses. In this case the analysis and equipment used in the
      analysis must have assured quality so that the correct clinical interpretation of
      the results is possible. The operation of a gait analysis laboratory may be
      described in quality standards terminology as the operation of a 'special
      process'. The operation of a special process requires that particular attention
      be paid to procedures including confirmation of the equipment and regular testing
      to ensure correct operation of the equipment. In general this is difficult to
      achieve since equipment manufacturers still have to address this technical
      requirement. Although difficult, these procedures must be accomplished in the
      operation of a special process. Passages of the most pertinent standards are
      presented and a methodology of a periodic confirmation and regular spot checking
      of equipment suggested to ensure its correct operation. Although force plates are
      specifically addressed, the framework could be applied to other dynamometers and
      measurement equipment.

PMID- 9255999
TI  - Bone registration method for robot assisted surgery: pedicle screw insertion.
AB  - A registration method that identifies bone geometry with respect to a robotic
      manipulator arm is presented. Although the method is generally applicable to many
      orthopaedic internal fixation procedures, it was only demonstrated for the
      insertion of pedicle screws in vertebral bodies for spine fixation. The method
      relies upon obtaining an impression of the vertebral bodies. Computerized
      tomography (CT) scans of both vertebrae and mould are reconstructed using a
      computer aided engineering (CAE) system. From the reconstructions, the surgeon is
      able to do preoperative planning including selection of pedicle screw diameter,
      direction of screw through pedicle, point of entry and length of engagement. The
      three-dimensional models are than meshed to determine positions of the surgeon's
      preoperative plan relative to the mould. Intra-operative positions are defined in
      space by a mechanical fixture rigidly attached to the mould and designed to allow
      a manipulator end-effector to recognize the global coordinates of the in vivo
      spine. The theory and methodology were validated using a five-axis manipulator
      arm. This initial presentation assumes and allows no relative motion between
      vertebrae in vivo.

PMID- 9256000
TI  - Parameter sensitivity of a mathematical model of the anterior cruciate ligament.
AB  - This paper presents the results of an investigation into parameter sensitivity of
      a mathematical model of the human anterior cruciate ligament (ACL). The model ACL
      comprised a continuous array of fibres mapped between part-elliptical attachment
      areas on the femur and tibia. Relative motion of the two bones was controlled by
      a planar four-bar linkage. Parameter modifications were: (a) an alternative set
      of values for the coordinates of the four-bar linkage joints; (b) rotation of the
      attachment areas of the ligament by +/- 30 degrees; and (c) variation of some
      mechanical properties. The alternative four-bar linkage parameter set produced
      extremely large changes in ACL force values, up to 130 per cent. Rotating the
      tibial attachment changed forces by less than 20 per cent, whereas rotating the
      femoral attachment changed forces by up to 100 per cent. Altering the mechanical
      parameters produced the smallest differences in force, under 15 per cent. These
      results highlight the importance, when using a theoretical model, of establishing
      the values of the parameters defining the model as accurately as possible and of
      carrying out a parameter sensitivity study. From a clinical viewpoint, they also
      suggest that, when reconstructing a ruptured ACL, one of the most important
      considerations must be to position the femoral attachment of the graft as
      accurately as is feasible.

PMID- 9256001
TI  - Analysis of fluid film lubrication in artificial hip joint replacements with
      surfaces of high elastic modulus.
AB  - Lubrication mechanisms and contact mechanics have been analysed for total hip
      joint replacements made from hard bearing surfaces such as metal-on-metal and
      ceramic-on-ceramic. A similar analysis for ultra-high molecular weight
      polyethylene (UHMWPE) against a hard bearing surface has also been carried out
      and used as a reference. The most important factor influencing the predicted
      lubrication film thickness has been found to be the radial clearance between the
      ball and the socket. Full fluid film lubrication may be achieved in these
      hard/hard bearings provided that the surface finish of the bearing surface and
      the radial clearance are chosen correctly and maintained. Furthermore, there is a
      close relation between the predicted contact half width and the predicted
      lubrication film thickness. Therefore, it is important to analyse the contact
      mechanics in artificial hip joint replacements. Practical considerations of
      manufacturing these bearing surfaces have also been discussed.

PMID- 9256002
TI  - Simultaneous measurement of stiffness and energy absorptive properties of
      articular cartilage and subchondral trabecular bone.
AB  - The purpose of this study was to develop a method for simultaneous measurement of
      the mechanical properties of articular cartilage and underlying trabecular bone.
      Cylindrical bone-cartilage specimens from human cadaver knees were tested under
      non-destructive axial compression. The specimens wer mounted in a cage by three
      screws fixed to the subchondral bone plate to create a reference plane between
      the cartilage and the bone. Each test was carried out as a single test cycle
      between a 0.12 MPa (4 N) pre-stress and 0.5 per cent bone strain. Twenty
      conditioning cycles were performed prior to each test cycle. In order to
      determine the reproducibility of the test method, the test procedure was repeated
      after turning the cage through 90 degrees. The specimens were then kept at +5
      degrees C for 24 hours, and the procedure was repeated. The normalized stiffness
      and energy absorptive properties were calculated from each test cycle. No
      significant difference was found between the results obtained on the first and on
      the second day. Both days the stiffness of cartilage was significantly larger
      during the second test, indicating that 20 conditioning cycles may not provide a
      viscoelastic steady state.

PMID- 9256003
TI  - Wear of ultra-high molecular weight polyethylene acetabular cups in a
      physiological hip joint simulator in the anatomical position using bovine serum
      as a lubricant.
AB  - The Leeds physiological anatomical (PA) hip joint simulator was developed to
      apply three axes of loading and a complex three-dimensional motion so that the
      forces and motions can reproduce exactly the walking cycles defined by Paul. This
      paper presents the results of a study using the Leeds PA hip joint simulator to
      determine the wear of 32 mm ultra-high molecular weight polyethylene (UHMWPE)
      acetabular cups against stainless steel and zirconia ceramic heads, using bovine
      serum as lubricant. These results have been compared with the results of a
      previous study that used water as the lubricant, which led to UHMWPE transfer
      film being formed on the stainless steel head. Comparisons are also made with
      clinical results and results from other simulators. The study indicates that it
      is preferable to use bovine serum in simulator studies. In addition, the results
      indicate that if the surface roughness of the metallic and femoral heads are
      similar, and they remain undamaged during the tests, the wear rates of the UHMWPE
      cups are likely to be similar.

PMID- 9256004
TI  - Estimation of loads and stresses in abdominal muscles during slow lifts.
AB  - Calculations are made of abdominal muscle loads and stresses associated with the
      development of intra-abdominal pressure during slow, symmetrical lifts. The
      muscles considered are the rectus, transversus and the external and internal
      obliques. Muscle loads and stresses have been calculated in an abdominal cross
      section at about the level of the third lumbar vertebra. For four cases examined,
      maximum stress levels for men in the 25-35 years age range appear to be 3p-4p for
      the rectus muscles, 15p-25p for the transversus and 4p-6p for the obliques, where
      p is the intra-abdominal pressure. Corresponding figures for a man aged 66 years
      are about 8p, 21p and 8p respectively.

PMID- 9256005
TI  - [Ischemic heart disease and apoptosis].
AB  - In the last three years, apoptosis has been reported to be associated with cell
      death in ischemic heart diseases, for examples, acute ischemic cardiomyocyte
      death in acute myocardial infarction; death of the salvaged cardiomyocytes in old
      myocardial infarction; death of infiltrated leukocytes and granulation tissue
      cells after myocardial infarction. Apoptosis-related proteins such as Bcl-2, Bax
      and Fas are expressed in the salvaged cardiomyocytes edging the infarct area. In
      vitro experiment using cultured cardiomyocytes suggested hypoxia causes apoptosis
      in them. Thus, apoptosis may play important roles in ischemic heart diseases. For
      detecting apoptosis, however, all of the previous studies on acute ischemic
      cardiomyocyte death depended exclusively on DNA fragmentation (biochemical marker
      of apoptosis) by a DNA ladder on gel electrophoresis and in situ nick end
      labeling (TUNEL), but never documented the ultrastructural changes characteristic
      of apoptosis (morphological marker of apoptosis). Then, we examined the
      ultrastructure and DNA fragmentation of cardiomyocytes in rabbit myocardial
      infarction using electron microscopy combined with TUNEL (EM-TUNEL) which allows
      simultaneous observation of both markers in the same cell. Rabbits underwent 30
      min ischemia followed by 0-, 30-min, 2-, 4- and 24-h reperfusion of a left
      coronary artery. In the infarcted tissue, EM-TUNEL revealed oncotic necrosis of
      cardiomyocytes with or without DNA fragmentation in the 2-h, 4-h, and 24-h
      reperfusion groups, but no apoptotic cardiomyocytes in ultrastructure in any
      groups. Thus, so-called apoptotic cardiomyocytes after ischemia/reperfusion may
      belong to a different category from apoptosis.

PMID- 9256006
TI  - [Thrombosis and apoptosis].
AB  - Apoptosis is a controlled form of cell death that allows the removal of cells
      during physiological or pathological processes. Recent studies suggested a
      potential link of apoptosis with processes leading to thrombophilia. In this
      review, we describe the mechanisms by which apoptotic cells would cause
      activation of blood coagulation and instability of atherosclerotic plaque leading
      to increased thrombus formation. A well-recognized acquired thrombophilia is the
      anti-phospholipid syndrome. Alterations of the phospholipid phase of cell
      membranes in the course of membrane blebbing, a characteristic morphological
      change occurring during the late apoptotic process, have been shown to be
      associated with the production of anti-phospholipid antibodies. These surface
      blebs on apoptotic cells have been shown to be the sites of enhanced procoagulant
      activity. Reversely, several anti-phospholipid antibodies may also induce
      apoptosis resulting in the formation of immunogenic and highly procoagulant
      surface blebs. Apoptosis was also found to be associated with increased cell
      surface tissue factor procoagulant activity, the so called tissue factor de
      encryption. Atherosclerotic plaque rupture is associated with increased thrombus
      formation. Apoptotic inflammatory cells such as macrophages and T cells are
      abundant in atherosclerotic plaque and may be related to plaque instability.
      During the process of endothelial cell apoptosis, a loss of the anticoagulant
      property of endothelial cell surface concomitantly with an increase in their
      adhesiveness for leukocytes might probably occur. These changes may be important
      for the rapid progression of the atherosclerotic process.

PMID- 9256007
TI  - [Apoptosis and myopathies].
AB  - Recently a new type of cell death, apoptosis, was reported in the biological and
      many other fields. In an attempt to determine whether the Fas-Fas-ligand mediated
      apoptosis operates in the pathologic process of human myopathies, we examined the
      expression of Fas antigen, the synthesis of Fas-ligand mRNA, and the presence of
      chromosomal DNA fragmentation in the muscles from patients with various human
      muscle disorders. The Fas antigen of a whole molecule that can transduces the
      apoptotic signal into the cytoplasm was expressed on the muscle fibers of
      patients with various muscle wasting diseases. Its expression on muscle fibers
      was not disease specific, and the frequency of it becomes high according to the
      extent of the alteration of the muscle pathology. However, there was no evidence
      of operating the apoptotic process, that is no DNA fragmentation by TUNEL method.
      Furthermore, no Fas-ligand synthesis was detected in the diseased muscle tissue
      by RT-PCR method. Our data suggest that the expression of Fas antigen on muscle
      fibers in diseased muscles might be related to unknown biological functions other
      than "apoptosis" in the process of muscle fiber injury.

PMID- 9256008
TI  - [Overexpression of bcl-2 suppresses apoptosis in the human leukemia cell line TF
      1].
AB  - It is generally recognized that bcl-2 gene strongly protects cells from apoptosis
      in various situations. But its function is still to be examined. We analyzed the
      effect of bcl-2 gene using growth factor dependent cell line, TF-1, derived from
      an erythroleukemia patient. On GM-CSF removal TF-1 (bcl-2) cells which were
      transfected with bcl-2 cDNA by retrovirus vector system survived and arrested in
      G0-1 phase of the cell cycle, while TF-1 (mock) cells which were transfected with
      vector only also arrested in G0-1 but decreased in number in several days and
      showed typical apoptosis. N-acetylcysteine, one of antioxidants, did not show
      such anti-apoptotic effect as bcl-2 in the preincubation experiment. By
      centrifugal elutriation system the G0-1 arrested subfraction of TF-1 (bcl-2)
      showed time delay at the re-entry into cell after GM-CSF re-addition when
      compared with the G0-1 arrested subfraction of TF-1 (mock). Similar delay in cell
      cycle progression was observed after 24hs-exposure of staurosporine, a protein
      kinase C (PKC) inhibitor. The expression of cell cycle genes including cyclin A,
      C, D1, E, cdk2, 4, c-myc, bax and bcl-x showed no difference between these two
      cell lines upon growth factor removal. These results imply that the functional
      commitment of bcl-2 into cell cycle progression under the situation of apoptosis
      especially at the restriction point of G1-S transition.

PMID- 9256009
TI  - [Apoptosis in uremic complication].
AB  - Chronic renal failure (CRF) is often complicated by lymphopenia and sometimes by
      hepatic dysfunction. To elucidate the involvement of apoptosis in these
      complications, we analyzed Fas antigen which mediates apoptosis on peripheral
      blood T cells and hepatic cells. T cells from uremic patients expressed Fas with
      higher intensity than control T cells. When cultured in vitro, uremic T cells
      were shown to undergo acceleratd apoptosis in correlation with Fas expression.
      Immunohistological analysis of liver tissues revealed that hepatocytes in
      patients both with chronic hepatitis and with CRF expressed higher levels of Fas
      than those in patients alone with chronic hepatitis. These results suggest that T
      cells and hepatocytes in CRF may undergo apoptosis by the Fas system.

PMID- 9256010
TI  - [Study of apoptosis in Sjogren's syndrome].
AB  - To clarify the role of apoptosis in the pathogenesis of Sjogren's syndrome (SS),
      we investigated apoptosis and apoptosis-related molecules in peripheral blood
      lymphocytes (PBL) and salivary glands (SG) from SS patients and normal controls.
      In PBL, SS T lymphocytes showed accelerated in vitro apoptosis, and CD4+ T cells
      showed increased Fas expression compared to those in normal controls.
      Interestingly, SS T cells also showed increased Bcl-2 expression. The acinar
      epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis.
      The majority of infiltrating lymphocytes in SS were Fas+ and Bcl-2+, while few
      lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell
      death among lymphocytes, particularly in dense periductal foci. Bax seemed to be
      expressed in apoptotic acinar cells. In conclusion, blocked apoptosis of SG
      infiltrating lymphocytes as well as enhanced apoptosis of peripheral T cells may
      be characteristics of SS. SS acinar cells may die by apoptosis, and this may
      ultimately lead to SG destruction in SS patients.

PMID- 9256011
TI  - [Microsatellite instability in gastric cancer with varied structure].
AB  - BACKGROUND: The intratumoral histological heterogeneity of cancer has been
      investigated by many pathologists. Although microsatellite alteration has been
      reported in gastric cancer, the significance of genomic instability in these
      histologically heterogeneous cases has not been elucidated. METHODS:
      Microsatellite alteration detected by polymerase chain reaction (PCR) in 13
      primary advanced gastric cancers with varied structure was examined at 8
      microsatellite loci. RESULTS: We were able to detect a greater prevalence of
      replication errors (RER) (6/13, 46.2%) at the primary site of gastric cancer than
      previously reported and loss of heterozygosity (LOH) at 17p (4/13, 30.8%) was
      demonstrated at the primary sites. All the same time, we also examined metastatic
      tumors in the regional lymph nodes in 12 of these cases. The frequency of RER
      (8/12, 66.7%) in metastatic lesions was higher than that in primary tumors.
      Detectability of RER was more frequent in the poorly differentiated portions than
      the well-differentiated portions of lymph node metastases. CONCLUSIONS: These
      findings suggest that gastric cancer with varied structure acquired frequent
      microsatellite instability during progression and metastasis, and we reasoned
      that the mutator phenotype detected by microsatellite alterations may represent
      heterogeneous tumor clones in gastric cancer and lymph node metastases.

PMID- 9256012
TI  - [The pituitary specific transcription factor Pit-1/GHF-1 and PIT1 abnormality].
AB  - Pit-1/GHF-1 is a pituitary specific POU-domain DNA binding factor, which
      transactivates the growth hormone (GH), prolactin (PRL), thyrotropin beta subunit
      (TSH beta) genes, and PIT1 gene itself. It is indispensable for the
      differentiation and the proliferation of the cells producing GH, and PRL. Loss of
      the PIT1 gene function (PIT1 abnormality) results in combined deficiency of GH,
      PRL, and TSH. PIT1 abnormality serves as a model of transcription factor
      abnormalities.

PMID- 9256013
TI  - [Pathologic diagnosis on bone and soft tissue tumors by molecular biological
      methods].
AB  - Characteristic chromosome aberrations and the rearranged genes resulting in
      chimeric fusion genes have been reported in some bone and soft tissue tumors;
      t(X; 18) in synovial sarcoma, t(11; 22) in Ewing's sarcoma and primitive
      neuroectodermal tumor, and t(2; 13) in alveolar rhabdomyosarcoma. We practically
      used the chromosome analysis and the reverse transcription-polymerase chain
      reaction (PCR) method as a tool for diagnosis and follow up. All of 10 cases of
      synovial sarcoma had a chimeric product of SYT/SSX gene. Eleven cases of Ewing's
      sarcoma and primitive neuroectodermal tumor showed 6 variants of chimeric
      products between EWS gene and Fli1 gene in the PCR-directed sequence analysis.
      Although PAX3/FKHD or PAX7/FKHD transcripts were amplified in alveolar
      rhabdomyosarcoma cases, MyoD1 and myogenin gene which are myogenic transcription
      factor were also expressed in most rhabdomyosarcomas. These findings indicate
      that molecular biological analysis may be a useful supplementary method for
      pathologic diagnosis of bone and soft tissue tumors.

PMID- 9256014
TI  - [Detection of nucleotide mutation by direct sequencing method using non-radio
      isotopic marker].
AB  - We report a protocol which can analyze DNA by the dideoxy method. First, we
      prepared DNA from paraffin specimen of colon cancer and normal tissue by the
      method using proteinase and phenol. Polymerase chain reaction (PCR) was performed
      as follows. The primers used were oligonucleotides corresponding to the sequence
      of exon 5 on p53. An initial denaturing step was carried out at 94 degrees C for
      2 min. Products were amplified for 40 cycles at 94 degrees C for 1 min, 60
      degrees C for 1 min, and 72 degrees C for 1 min. Specific PCR products derived
      from p53 gene were purified. Protocol for the PCR-sequencing reaction: The
      reaction mixture was divided into four 4 microliters fraction. Each fraction was
      mixed with 2 microliters of NTP solution including non-RI dideoxynucleotides
      (TOYOBO). PCR was carried out as follows: an initial denaturing step at 94
      degrees C for 1 min, then 30 cycles at 94 degrees C for 1 min, 60 degrees C for 1
      min, and 72 degrees C for 1 min. Prior to loading in a denaturing 8%
      polyacrylamide-6M Urea gel, the samples were heated to 94 degrees C for 2 min
      then quickly chilled in ice-water. Electrophoresis was carried out at 1000V for
      3hr and transcribed to a nylon membrane. The ladders of DNA were obtained by Non
      RI Detection Kit (TOYOBO). We determined the sequence of 167 nucleotides. Results
      indicated that the point mutations in DNA could be easily detected.

PMID- 9256015
TI  - [Monitoring of inhibitors of the polymerase chain reaction for the detection of
      hepatitis C virus using the positive internal control].
AB  - In the direct detection of pathogens by polymerase chain reaction (PCR) from
      clinical samples, false negative results due to the presence of inhibitor are
      problematic. In order to monitor such an inhibitor, we evaluated the detection of
      the positive internal control in PCR assay for HCV-RNA in serum samples positive
      for anti-HCV antibodies, of which 41 samples were positive for HCV-RNA by
      competitive RT-PCR assay. The positive internal control was coamplified with HCV
      RNA and hybridized to the specific probe on magnetic beads and then hybrids were
      detected by colorimetric measurement using automatic PCR machine (COBAS
      AMPLICOR). Detection of the positive internal control was negatively correlated
      with viral copy number in sera assayed by competitive RT-PCR. Five of 52 samples
      (9.6%) with high HCV-RNA copy number (10(7) or 10(8) copies/ml) showed negative
      results for the internal control. The negative results for the internal control
      turned out to be positive when the sera were diluted and re-assayed, suggesting
      competitively inhibitory effects of high viral copy number on amplification of
      the internal control. Addition of heparin in the serum sample showed an
      inhibitory effect with a dose dependent manner on the detection of both HCV-RNA
      and the internal control, with a more effect on the lower copy number of HCV. On
      the other hand, addition of hemoglobin in the sample with concentration of up to
      450mg/dl had no inhibitory effect on the detection of either HCV-RNA or the
      internal control. Coamplification and detection of the positive internal control
      was demonstrated to be useful to estimate effects of inhibitors, which may be
      present in clinical samples, in the detection of HCV-RNA by PCR.

PMID- 9256017
TI  - [Spectrum analysis of heart rate variability for the assessment of training
      effects].
AB  - The aim of our study was to investigate the effect of habitual exercise on the
      autonomic nervous system on the basis of spectral analysis of heart rate
      variability. We studied 24 healthy subjects. Eight were trained athletes (age
      26.9 +/- 12.4 years, weight 58.6 +/- 7.9 kg, BMI 21.7 +/- 2.6 kg/m2) who
      routinely performed a minimum of 40 minutes of aerobic activity per week. The
      control population was represented by 16 untrained persons (age 27.1 +/- 11.9
      years, weight 59.1 +/- 13.0kg, BMI 22.1 +/- 4.0kg/m2). There was no significant
      difference in age, gender, weight and BMI between two groups. After 10 minutes of
      supine resting, all subjects were instructed to perform 40W exercise on a
      mechanically braked bicycle ergometer for 10 minutes. Heart rate was continuously
      recorded according to the experimental protocol. Low and high frequency power
      were calculated by using fast Fourier transform. Differences of parameter values
      between two groups were examined by using t tests. Before loading, the athletes
      had a significantly lower heart rate (63.7 +/- 4.0 beats/min) than control
      subjects (73.0 +/- 9.1 beats/min). During ergometric loading, the coefficient of
      variation of heart rate (CV) and the high frequency power (HF) were significantly
      higher, and low frequency power (LF) was significantly lower in the athletes (CV
      2.9 +/- 0.6, HF 0.5 +/- 0.2, LF 0.4 +/- 0.2) compared with the control subjects
      (CV 2.1 +/- 0.8, HF 0.3 +/- 0.1, LF 0.6 +/- 0.1). After loading, the athletes had
      a significantly lower heart rate. In conclusion, we found that there were
      significant differences in the spectral components of heart rate variability
      during exercise between athletes and control subjects. The results show that
      physical training could possibly increase parasympathetic activity (or decrease
      sympathetic activity).

PMID- 9256016
TI  - [Application of urinary free dopamine as a marker of renal function, and
      comparison with other renal marker].
AB  - Urinary free dopamine (U-f-DA) is derived from renal DA synthesized in the renal
      proximal tubules, and plays an important role for diuresis and natriuresis. We
      were previously reported that U-f-DA was the superior marker of renal function as
      compared with ordinary methods including alpha 1-microglobulin (U-alpha 1 MG),
      beta 2-microglobulin (U-beta 2 MG) and N-acetyl-beta-D-glucosaminidase (U-NAG) in
      spot urine samples. U-f-DA can be used as index for the evaluation of renal
      transplantation. In order to evaluate the clinical usefulness of U-f-DA as a
      marker of renal function, we investigated as follows; firstly, the age related
      changes of U-f-DA in healthy out-patients, secondly, the correlation between U-f
      DA and creatinine clearance (CCr), serum creatinine (S-Cr) in in-patients, and
      thirdly, the chronological changes of U-f-DA, U-alpha 1 MG, U-beta 2 MG, CCr and
      S-Cr in patients with chronic renal failure before and after renal
      transplantation. There is no age-related changes in U-f-DA from patients with 3
      years to 88 years old. U-f-DA was positively correlated with CCr and negatively
      correlated with S-Cr. There are parallel changes of U-f-DA and CCr in increasing
      direction, on the other hand, parallel changes of U-alpha 1 MG, U-beta 2 MG and S
      Cr in decreasing direction after renal transplantation. In patients with post
      renal transplantation who were not well controlled, S-Cr increased gradually with
      the decreasing level of U-f-DA. These results suggest that the measurement of U-f
      DA in spot urine samples is useful marker for evaluation of the renal function
      and can be used an index of viability of the transplanted kidney.

PMID- 9256018
TI  - [Determination of in vitro synergy when amphotericin B is combined with various
      antimicrobial agents against yeasts by using a colorimetric microdilution
      checkerboard].
AB  - We determined in vitro interactions when amphoteric B (AMPH) is combined with
      various antimicrobial agents against yeast by using a colorimetric microdilution
      transfer plate technique, principally based on the current National Committee for
      Clinical Laboratory Standards (NCCLS) M27-T. An oxidation-reduction dye, sodium
      resazurin, was used as a color indicator to detect the growth of yeasts, and a
      standard two-dimensional, two-agent microdilution checkerboard in RPMI 1640 was
      employed to determine in vitro interactions; synergistic, indifferent or
      antagonistic. The study included 125 clinical isolates of Candida species and
      nine reference strains of American Type Culture Collection described in M27-T.
      Among the 34 antimicrobial agents first tested, polymyxin B (PL), rifampicin
      (RFP), tetracycline (TC) and erythromycin (EM) showed significant synergism. The
      fractional inhibitory concentration (FIC) indices of the respective agents were;
      PL 0.16 to 0.51 (mean, 0.315), RFP 0.13 to 0.56 (0.255), TC 0.06 to 0.75 (0.353)
      and EM 0.27 to 1.0 (0.550). RFP was the most potent agent, 118 of 125 clinical
      isolates (94.4%) showing synergism (FIC, < or = 0.5). With these results, we can
      conclude that several antibacterial agents are potentially effective when
      combined with AMPH against yeasts, probably due to alteration in the permeability
      barrier of the surface membrane by AMPH. Antifungal synergism may be promising
      for more effective, and less toxic therapy, and thus in vivo study will be
      necessary to determine their clinical significance.

PMID- 9256019
TI  - [Day to day changes in SAA (serum amyloid A) values of healthy subjects and the
      effect of dexamethasone administration].
AB  - Serum amyloid A (SAA) is a sensitive acute phase reactant; its serum level
      increases up to 1,000 fold of the healthy level (less than 10 micrograms/ml).
      Recently, the diagnostic usefulness of this protein in comparison with C-reactive
      protein (CRP) has been discussed in disorders or situations which show slight
      elevation of these protein levels, especially, in subjects receiving
      glucocorticoid therapies. To clarify physiological changes of this protein, day
      to day variations in SAA values of 23 healthy individuals were investigated and
      it was shown that majority (91%) had dynamic ranges of less than 3.0
      micrograms/ml. Effect of dexamethasone administration on SAA and CRP values was
      studied in 10 subjects who received a dexamethasone suppression test. Changes in
      SAA values were within the physiological variation, and discrepancy in the
      changes between SAA and CRP as previously described in subjects with
      glucocorticoid therapies was not shown.

PMID- 9256020
TI  - Evaluation of the safety of cantastim in normal humans.
AB  - CANTASTIM, a good immunomodulatory agent obtained from a highly pathogenic strain
      of Pseudomonas aeruginosa was inoculated during 12 weeks in 21 healthy
      individuals aged 18-45 years. The subjects were clinically and laboratory
      investigated for body weight, antibodies against DNA, collage, cardiolipin,
      number of blood cells, blood and urine enzymes etc. After this intensive therapy,
      all the studied parameters were found in normal range of values. The results are
      a proof that this immunomodulator is not antigenic and has not side effects.

PMID- 9256021
TI  - DNA cell cycle analysis of K562 and Ehrlich tumor cells by flow cytometry.
AB  - Monitoring cell activation processes and cell cycle progression in cells of
      various ontogenetic and phylogenetic origins is one of the base challenges in
      cellular biology. Flow cytometric analysis by DNA histograms show the cell cycle
      distribution and indicate the S-phase fractions of cell populations, as well as
      those cells in Go/G1 and G2/M phases. Human and murine normal diploid cells, K562
      tumor cells (human origin) and Ehrlich cells (murine origin) were analysed using
      a propidium iodide staining procedure for flow cytometry. Our preliminary results
      suggested that this method may be a useful tool to detect cell populations with
      quantitative changes in DNA content, and to estimate cell fractions.

PMID- 9256023
TI  - Experimental study of the mixed (oral-intradermal) vaccination method in enteric
      diseases.
AB  - Enteric vaccines are currently administered in man either orally or parenterally,
      each vaccination route having its advantages and disadvantages. In an attempt to
      cumulate the favourable effects of the two immunization methods a combined (oral
      intradermal) anti-S.typhimurium and anti-S.typhi vaccination scheme was applied
      in mice. For comparison reasons, the oral (one or two immunization cycles) and
      the parenteral (one or two vaccine doses intradermally administered) vaccinations
      were used. The results obtained showed that mixed (oral-intradermal) vaccination
      induces a higher protective effect to infection with S.typhimurium or S.typhi, as
      compared to the single oral vaccination (one or two cycles) and a protective
      effect which does not differ from that obtained by intradermal vaccination.

PMID- 9256022
TI  - Serodiagnosis of tuberculous meningitis by enzyme-linked immunosorbent assay
      (ELISA).
AB  - IgG antibodies against glycolipids and proteins isolated from M. tuberculosis and
      BCG suspension were determined by ELISA in sera, in CSFs and in serum and CSF
      paired samples, from patients with tuberculous meningitis and from healthy
      control subjects. With specificities between 90 and 94% for the antigens used, we
      obtained senitivities of 75% for Pr-ELISA, 60% for G1-ELISA and 35% for BCG
      ELISA. As specific antibodies were detected in serum and CSFs, only one sample is
      enough to perform the test. We concluded that Pr-ELISA and G1-ELISA could be used
      as a supporting test in TBM diagnosis, especially when repeated bacteriological
      methods failed to prove the presence of tubercle bacilli and in cases without
      evidence of pulmonary tuberculosis.

PMID- 9256025
TI  - Study of the sensitivity to antimicrobial drugs of some S. pneumoniae strains
      isolated from different pathological states.
AB  - 76 Str.pneumoniae strains isolated from different clinical disease forms were
      studied for the sensitivity to antimicrobial drugs using the diffusimetric method
      and the dilution in agar method (MIC to penicillin). The results revealed that
      44.74% of pneumococci were sensitive to penicillin, the remaining pneumococci
      being resistant; 18.42% showed a high resistance (MIC > or = 2 micrograms/ml). A
      close relationship was seen between sensitivity to penicillin on the one hand and
      the Pneumococcus origin and serotype on the other. As concerning the
      multiresistance to antimicrobial drugs, 47.4% of the strains presented resistance
      to > or = antibiotics belonging to different classes, the most frequent
      resistance pattern being P, E, Te, SxT. The most active antimicrobial drugs were
      vancomycin, amoxiclave, rifampicin, followed by ceftriaxone and amoxicillin.

PMID- 9256024
TI  - Biochemical and cytogenetical study of the mycoplasmal antigen and of the
      cyclophosphamide action in mammalians, in vivo. The action of some
      immunomodulatory antioxidants.
AB  - It was proved spectrophotometrically that Mycoplasma agalactiae antigen
      inoculated in vivo in sheep modifies the corresponding erythrocyte lysates
      reactivity toward methylene blue and neutral red and induces several types of
      chromosomal rearrangements. The treatment in vivo of sheep with an original
      preparation obtained from the Phaseolus vulgaris pods restores the erythrocyte
      lysates reactivity toward the two redox dyes and reduces the chromosomal
      abnormalities frequency induced by the mycoplasmal antigen. It was also
      demonstrated by optical and electronical microscopy that the Smise line mouse
      meiocytes exhibit chromosomal abnormalities induced by the cyclophosphamide
      treatment in vivo. In the case of concomitant treatment with the cyclophosphamide
      and C vitamin the same frequency of abnormalities was recorded as in the simple
      treatment with the drug.

PMID- 9256026
TI  - Development of resistance in Shigella flexneri isolates obtained in the past 20
      years in eastern Romania.
AB  - Our study is focused on the antimicrobial activity for a number of 626 Shigella
      flexneri strains collected from epidemic outbreaks and hospitalised patients
      during 1976-1995 period, in Eastern Romania. The metodology used for determining
      the in vitro activity of the antimicrobials was that described by NCCLS. The
      agents which are currently used in therapy (ampicillin, tetracycline,
      chloramphenicol) are less active than the newer drugs (third generation
      cephalosporins, aztreonam, imipenem, ciprofloxacin) for which sensitivity ranged
      between 93-100% The associated resistance between ampicillin, tetracycline,
      chloramphenicol was demonstrated. Isolates with MIC values for ampicillin > 8
      micrograms/ml are still sensitive to the modern beta-lactams. For
      ampicillin/sulbactam association, sensitivity decreases from 100% in 1990-1993 to
      43% in 1994-1995.

PMID- 9256027
TI  - Aspects of hydatidosis in the adult population in Banat.
AB  - An epidemiological study was performed on a lot of 505 adult subjects (over 20
      years old) diagnosed with E.granulosus hydatidosis and operated in surgery units
      in hospitals from such towns as Timisoara, Arad and Resita (1985-1992). The
      incidence of hydatid infection was almost uniformly distributed by sexes, being a
      little higher in rural areas (52.0%); the highest number of cases was reported in
      Timis County (63.6%), followed by Caras-Severin County (21.2%). Hydatidosis was
      most frequently found in liver (67.5%) and lungs (23.7%) and more rarely in
      kidneys (0.4%), brain (0.2%), pancreas (0.2%), ovary (0.2%). Secondary
      hydatidosis was reported on 12.7% of cases and multiple cyst forms in 12.7% of
      cases. The distribution of cases by age group was relatively balanced, a slightly
      increased incidence being found in the 20-29 years age group (23.2%), about 1/3
      of pulmonary localizations being reported in the age group. Post-surgery
      complications were reported in 13.5% of the total hepatic localizations and in
      30% of the pulmonary localizations. The average number of days in hospital was
      29.5 days/case. The average morbidity in the adult population in Banat over an
      eight years time interval was 5.36%ooo, being higher in Timis county-7.8%ooo
      where a peak (11%ooo) was reported in 1987.

PMID- 9256028
TI  - [Treatment with pilocarpine hydrochloride for sicca symptoms in Sjogren's
      syndrome].
AB  - We studied the efficacy of oral pilocarpine hydrochloride (9 mg/day, three times
      daily) on sicca symptoms in 21 patients with Sjogren's syndrome (SS) of the
      patients, 19 continued the treatment for at least one month, and subjective
      improvement of dry mouth and dry eye was observed in 10 patients (53%) and 5
      patients (26%), respectively. As adverse effects, diaphoresis was most frequently
      recognized, but it was generally mild and tolerable. In the four patients who
      have been taking pilocarpine for 12 months, any severe side effects have not been
      observed. Since the incidences of clinical improvement of sicca symptoms and
      adverse effects were comparable with the other studies reported from US or
      Europe, our treatment protocol using pilocarpine hydrochloride (9 mg/day) was
      considered as appropriate for Japanese SS patients.

PMID- 9256029
TI  - [Antigenic epitopes recognized by autoantibodies to calpastatin in patients with
      rheumatoid arthritis and their clinical significance].
AB  - We have previously described that novel autoantibodies to calpastatin (endogenous
      inhibitor for calcium-dependent neutral protease, calpain) were detected in
      patients with rheumatoid arthritis (RA) and other disorders. Since calpain is
      thought to mediate inflammatory process and cartilage destruction, autoantibodies
      to its inhibitor protein, calpastatin, may be involved in the pathogenic
      mechanism of rheumatoid arthritis. In the present study, we analyzed antigenic
      epitopes reactive with autoantibodies to calpastatin and their clinical
      correlation. cDNA encoding the C-terminal 178 amino acids of human calpastatin
      (RA-6) was digested by restriction enzymes and ligated in to pEX expression
      vectors. These recombinant plasmids were tranfected into E. coli POP2136 and
      screened by colony blots using RA sera containing anticalpastatin antibodies and
      a mouse monoclonal antibody. RA patient sera recognized the C-terminus of domain
      IV (epitope C1 ; aa. 647-673) and C-terminus of domain III (epitope C2 ; aa. 496
      571), whereas the mouse monoclonal antibody recognized an entirely different
      region containing the calpain-binding site (epitope B2 ; aa. 572-625). To
      evaluate epitope reactivity of patient autoantibodies, 15 RA sera containing anti
      calpastatin were reacted with epitope fusion proteins. In immunoblotting, most RA
      sera recognized either C1 or C2 epitopes (67% and 40%, respectively), and only
      one patient recognized both epitopes. B2 epitope a more progressed and sever
      state of arthritis than those not reacting with C1. These results suggests that
      anti-calpastatin antibodies may play a role in the pathogenic mechanisms of RA
      and their epitope reactivity may be important for disease progression.

PMID- 9256030
TI  - [A new approach to assessing rheumatoid arthritis (RA) disease activity using the
      American College of Rheumatology core set of disease activity measures for RA
      trials--a multi-center study].
AB  - To characterize the American College of Rheumatology core set of disease activity
      measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures)
      and the ACR definition of improvement of RA (ACR improvement definition), we
      studied 42 Japanese patients with active RA who were treated with DMARDs
      including mizoribine. Each patient's disease activity was assessed at the time of
      enrollment to the study and after 24 weeks using the ACR core set measures as
      well as the physical global assessment through the conventional measures. Twenty
      five (60%) patients were discerned as showing improved by physicians through the
      conventional measures. This decision appeared to be based on improvement in
      Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the
      25 "improved" patients satisfied the ACR improvement definition. The 12 patients
      showed significant improvement in "outcome" measures including patients
      assessments of pain, disease activity, and physical function, compared to the 30
      patients not satisfying the ACR definition. However, no significant differences
      were observed between these two groups in "process" measures including LAI,
      tender joint count, swallen joint count, or CRP value. In conclusion, the ACR
      core set measures including both process and outcome measures have potential to
      reflect clinical important changes on "real life" of patients with RA.

PMID- 9256031
TI  - [Crescentic glomerulonephritis in a patient with rheumatoid arthritis].
AB  - A 56-year-old female with rheumatoid arthritis was admitted because of bilateral
      hip pain. In a few months of her hospitalization, a relatively abrupt renal
      dysfunction was emerged besides complement breakdown, and renal biopsy revealed
      crescentic glomerulonephritis. Immunofluorescence study showed peripheral
      granular deposits of IgG, IgM, and C3 in the glomeruli. Cresents were
      predominantly composed of macrophages and glomerular epithelial cells. Amyloid
      nephropathy, renal vasuculitis, and association of other collagen vascular
      diseases were negligible for the causative factor. It was suggested that immune
      complexes were formed in the glomeruli, in which both humoral and cellular immune
      responses were to be induced, that brought cescents formation in the lesions.
      Crescentic glomerulonephritis in patients with rheumatoid arthritis is rare and a
      possible pathogenetic mechanisms involved in the development of renal dysfunction
      are discussed with the special reference to immune complex-induced inflammation.

PMID- 9256032
TI  - [A case of MPO-ANCA positive progressive systemic sclerosis with status
      epileptics].
AB  - A 37-year-old female, who had been suffering from progressive systemic sclerosis
      (PSS) with long-term renal failure, was diagnosed as MPO-ANCA positive PSS in
      active stage. She had systemic scleroderma, normotensive renal failure and
      pulmonary fibrosis. Respiratory management and steroid therapy under the control
      of CVVH were done for her treatment. She developed hemolytic anemia and
      thrombocytopenia during the treatment. She was diagnosed as microangiopathic
      hemolytic anemia, and was treated with plasma exchange treatment. About eight
      weeks after her admission, she developed status epileptics. Cerebral computed
      tomography and lumbar puncture did not reveal any abnormal sign. The case
      reported herein is a MPO-ANCA positive PSS with normotensive renal failure.
      Generally, PSS rarely reveals neurological sign. This case suggests possibility
      of association between MPO-ANCA and systemic vasculitis in PSS.

PMID- 9256033
TI  - [A case of macrophage activation syndrome developed with systemic juvenile
      rheumatoid arthritis].
AB  - We reported a child of macrophage activation syndrome (MAS) associated with the
      course of systemic juvenile rheumatoid arthritis (sJRA). The clinical and
      laboratory findings in our case was ascribed to the overproduced inflammatory
      cytokines especially TNF-alpha by activated macrophages. Moreover, macrophage
      colony stimulating factor (M-CSF) was also elevated in the active phase of the
      disease, and decreased in the convalescent phase, indicating that M-CSF can be
      the most potent stimulator of macrophages to produce inflammatory cytokines.
      Cyclosporine A along with plasmaexchange and corticosteroid, instead of VP16 or
      other immunosuppresive agents, was effecting in the management of this severe,
      life-threatening MAS.

PMID- 9256034
TI  - [Two cases of remitting seronegative symmetrical synovitis with pitting edema].
AB  - We report 2 elderly patients who present with a relatively acute onset of a
      severe symmetrical synovitis affecting the flexor digitorum tendon sheaths and
      wrist joints with pitting edema of the dorsum of both hands. These patients were
      seronegative for rheumatoid factor and responded to treatment with low dose
      predonisone (10 mg daily) without relapse. These presenting features were closely
      linked with the RS3PE syndrome originally described by McCarty.

PMID- 9256035
TI  - [Successful treatment of toe gangrene with moderate-dose steroid therapy in a
      patient with systemic sclerosis (CREST syndrome)].
AB  - A 68-year-old woman first noticed Raynaud's phenomenon at the age of 35, and she
      was diagnosed as having systemic sclerosis (SSc) because of cutaneous calcinosis,
      sclerodactyly, telangiectasia, sausage-like finger, digital pitting scar in 1971.
      In October, 1994, she was suffered from cold sensation in her right foot, and on
      November 2 she noticed the painful ulcers on the right toe, which progressed to
      be gangrenous. Every antiplatelet or thrombolytic agents including PGE1,
      argatroban, sarpogrelate hydrochloride and urokinase were unsuccessful.
      Angiograms revealed marked narrowing of bilateral anterior and posterior tibial
      and peroneal arteries. Prednisolone 30 mg/day was started, which resulted in
      successful response within 10 days. Large vessel involvement in SSc patients has
      been reported to be rare, and its treatment remains to be established. We believe
      our case help understanding the pathophysiology of such rare manifestation in
      SSc.

PMID- 9256036
TI  - [Recent concept and clinical manifestations of reactive arthritis].

PMID- 9256037
TI  - River blindness (onchocerciasis). Progress in ivermectin distribution.

PMID- 9256038
TI  - Expanded programme on immunization (EPI). Progress towards measles elimination.

PMID- 9256039
TI  - Medicaid managed care train on track.

PMID- 9256041
TI  - We hear you.

PMID- 9256042
TI  - Front-runner.

PMID- 9256044
TI  - Seed money.

PMID- 9256043
TI  - Texas physicians led fight to pass tough tobacco-control laws for minors.

PMID- 9256045
TI  - Explore very young children's conceptions of "self" and "other".

PMID- 9256046
TI  - Learning about self and other during requests.

PMID- 9256047
TI  - What language reveals about children's categories of personhood.

PMID- 9256048
TI  - The portrayal of negative emotions during mother-child pretend play.

PMID- 9256049
TI  - Young children's presentations of self in conversational narration.

PMID- 9256050
TI  - Self in relation to other: preschoolers' verbal social comparisons within
      narrative discourse.

PMID- 9256051
TI  - Naturalistic observation of children with autism: evidence for intersubjectivity.

PMID- 9256052
TI  - The recently-described ascidian species Molgula tectiformis is a direct
      developer.
AB  - Molgula tectiformis is a new ascidian species recently described by Nishikawa
      (1991). In Otsuchi Bay, Iwate, Japan, they are easily obtainable from cages for
      culturing scallops. We report here that M. tectiformis is another example of a
      direct developer: their embryonic development is lacking the tadpole larva. The
      fertilized egg is orange and about 150 microns in diameter. At 18 degrees C, the
      egg cleaves at about 20 min intervals and gastrulation occurs about 5 hr after
      fertilization. In contrast to conventionally-developing ascidians, M. tectiformis
      does not form a tadpole larva. Immediately before hatching, three stolons or
      ampullae begin to extend from the tailless embryo. After hatching the stolons
      mediate the attachment of the juvenile body to the substratum. Histochemistry for
      tissue-specific enzyme activity did not detect muscle-specific acetyl
      cholinesterase, endoderm-specific alkaline phosphatase, and pigment cell-specific
      tyrosinase. In addition, in situ hybridization could not prove the presence of
      muscle actin gene transcripts in the embryo. These results suggest that these
      larval tissues do not differentiate in M. tectiformis embryos. Because M.
      tectiformis is common and gravid year-around in Otsuchi Bay, this direct
      developer provides the opportunity for further analysis of molecular changes
      during evolution that cause an alternative mode of development.

PMID- 9256053
TI  - Outbreak of cyclosporiasis--northern Virginia-Washington, D.C.-Baltimore,
      Maryland, metropolitan area, 1997.
AB  - During July 1997, state and local health departments in Virginia, the District of
      Columbia (DC), and Maryland received reports of clusters of cases of
      cyclosporiasis associated with events (e.g., luncheons) held in their
      jurisdictions during June and July. This report describes the preliminary
      findings of the investigation of a cluster in Virginia and summarizes the
      findings from ongoing investigations of the other clusters. Fresh basil has been
      implicated as the probable vehicle of infection.

PMID- 9256054
TI  - Status of the global laboratory network for poliomyelitis eradication, 1994-1996.
AB  - In 1988, the World Health Assembly adopted the goal of global poliomyelitis
      eradication by the year 2000. Since then, appropriate strategies have been
      developed, and substantial progress toward the implementation of these strategies
      has been reported from each region of the World Health Organization (WHO). The
      establishment of sensitive surveillance systems to detect polio cases and
      poliovirus is critical to guide program activities and eventually permit the
      certification of polio eradication. This report describes the proficiency of the
      global laboratory network, which operates in each WHO region and provides
      virologic laboratory support to all countries with endemic polio.

PMID- 9256055
TI  - Tuberculosis morbidity--United States, 1996.
AB  - During 1996, a total of 21,337 cases of tuberculosis (TB) (8.0 cases per 100,000
      population) were reported to CDC from the 50 states, the District of Columbia
      (DC), and New York City; this total represents a 6.7% decrease from 1995 (22,860
      cases [8.7 per 100,000 population]). This is the fourth consecutive year that the
      number of reported TB cases has decreased (Figure 1), resulting in the lowest
      number and rate of reported TB cases since national reporting began in 1953. This
      report summarizes TB surveillance data for 1996 and compares these data with
      selected data for previous years. The findings indicate a continuing decrease in
      the number of TB cases among U.S.-born persons and a leveling or slight decrease
      in the number of cases among persons born outside the United States and its
      territories (i.e., foreign-born).

PMID- 9256056
TI  - Isolation of E. coli O157:H7 from sporadic cases of hemorrhagic colitis--United
      States. 1982.

PMID- 9256057
TI  - The proliferating cell nuclear antigen (PCNA) gene family in Zea mays is composed
      of two members that have similar expression programmes.
AB  - PCNA is an auxilliary protein for DNA polymerase delta whose function is to
      increase both polymerase activity and processivity. We have previously reported
      the isolation of a maize cDNA clone encoding a homologue of PCNA. Here we report
      the identification of a second maize PCNA cDNA clone. The nucleic acid sequence
      of both clones is almost identical in the coding sequences, showing 94% identity,
      but differs by approximately 40% in the 5' and 3' non-translated regions. Maize
      genomic Southern blots probed with the complete cDNAs and gene-specific probes
      revealed that maize contains two PCNA genes. Northern blots of RNA extracted from
      different plant tissues show that both genes are equally expressed in
      proliferating tissues.

PMID- 9256058
TI  - cDNA sequence of a translational elongation factor Ts homologue from
      Caenorhabditis elegans: mitochondrial factor-specific features found in the
      nematode homologue peptide.
AB  - The cDNA for a homologue of elongation factor Ts which probably functions in
      mitochondria has been sequenced from a nematode Caenorhabditis elegans. The
      deduced amino acid sequence (316 amino acids long) has a possible transit peptide
      sequence at the amino terminus and several common specific features for mammalian
      mitochondrial EF-Ts. The amino acid identities in the protein from C. elegans
      compared with those of bovine mitochondria and Escherichia coli are 29.5% and
      24.0%, respectively. The C. elegans sequence was classified as a long EF-Ts (ca.
      280 amino acids long) similar to peptides from mammalian mitochondria and
      eubacteria other than Thermus and cyanobacteria (except Spirulina platensis),
      rather than short EF-Ts (ca. 200 amino acids long) as those of Thermus,
      cyanobacteria and plastids.

PMID- 9256059
TI  - Isolation of a cDNA encoding a widely expressed novel zinc finger protein with
      the LeR and KRAB-A domains.
AB  - We have isolated a human cDNA clone representing a novel human gene. The
      predicted 683-amino-acid protein, designated FPM315, contains nine C2H2-type zinc
      finger motifs and two regions homologous to the LeR domain, a finger-associated
      structural domain, and the A element of the Kruppel-associated box (KRAB) domain
      involved in transcriptional repression. The FPM315 mRNAs were expressed in all
      human tissues so far examined. A cross-species genomic hybridization indicates
      that the FPM315 gene is highly conserved among eukaryotes. These data suggest
      that FPM315 might play an important role in basic cellular processes.

PMID- 9256060
TI  - ppt-1, a Neurospora crassa PPT/PP5 subfamily serine/threonine protein
      phosphatase.
AB  - We isolated a N. crassa cDNA clone encoding a novel-type serine/threonine
      phosphatase. The gene (mapped to LGVR), designated ppt-1, encodes a 479 amino
      acid putative polypeptide which contains a conserved tetratricopeptide repeat
      (TPR) motif. ppt-1 transcript levels are abundant in conidia and decrease during
      germination, indicating that ppt-1 is developmentally regulated.

PMID- 9256061
TI  - Molecular cloning of cDNA encoding a human TFEC isoform, a newly identified
      transcriptional regulator.
AB  - TFEC is a transcriptional repressor originally identified in rat chondrosarcoma
      and contains a basic helix-loop-helix and leucine zipper (bHLH/LZ) structure.
      TFEC shares a closely related bHLH/LZ structure with microphthalmia-associated
      transcription factor (MITF) and TFE3. In the course of cDNA cloning for a factor
      structurally related to MITF which is also a regulator for cell differentiation,
      we have isolated cDNA clones from a THP-1 human monocytic leukemia cell line.
      These cDNAs encode a protein of 347 amino acids, termed TFECL, a human homolog of
      a putative rat TFEC isoform. TFECL contains an acidic domain that corresponds to
      a transcriptional activation domain of TFE3 but its equivalent region is deleted
      in rat TFEC. We explored a function of TFECL using a melanocyte-specific
      tyrosinase gene and a ubiquitously expressed heme oxygenase-1 gene, each promoter
      containing the cis-acting CANNTG motifs. By transient coexpression assays, we
      showed that TFECL is able to activate or inhibit transcription of a reporter gene
      linked to either the tyrosinase or the heme oxygenase-1 gene promoter, depending
      on cell types. These results suggest that TFECL may function as a transcriptional
      activator under certain conditions.

PMID- 9256062
TI  - Constitutive activity of the murine IL-1 beta promoter is regulated by a
      transcriptional repressor.
AB  - Constitutive expression of IL-1 beta is kept under tight control in healthy
      tissues. So far no repressor elements down-regulating expression of the IL-1 beta
      gene have been described. In the current study, a deletion analysis approach was
      utilized to identify a region spanning -306/-292 bp upstream of the transcription
      start site, which appeared to down-regulate constitutive IL-1 beta promoter
      activity. Further deletion analysis confirmed that the -306/-292 bp element
      possessed repressor activity. A putative NF-kappaB binding site and an AATATT
      palindromic sequence were identified within the 306/-292 bp element. Notably, no
      binding of NF-kappaB was observed in gel shift assays, suggesting that another
      nuclear activity binding to the 14 bp sequence suppressed NF-kappaB binding.
      Further, the results of gel shift assays demonstrated that the AATATT palindromic
      sequence, which lies immediately downstream of the putative NF-kappaB site, may
      be responsible, in conjunction with the NF-kappaB site, for constitutive
      suppression of the IL-1 beta promoter. Thus, our results suggest that a novel
      repressor element may play a potentially important role in suppressing
      constitutive activity of the IL-1 beta promoter.

PMID- 9256063
TI  - Human gene for the RNA polymerase II seventh subunit (hsRPB7): structure,
      expression and chromosomal localization.
AB  - The human gene for the seventh largest subunit of RNA polymerase II complex,
      hsRPB7 was cloned, sequenced and mapped. This complex is an integral part of the
      transcription-coupled DNA repair mechanism and has been shown to be involved in
      several human genetic diseases and implicated in many others. The hsRPB7 gene
      consists of 8 exons and spans approximately 5.1 kb. Southern blots of genomic and
      cloned DNA suggest that hsRPB7 is coded for by a single gene. Using human
      radiation hybrids and YACs, the gene was localized to 11q13.1, within 70 kb of
      marker D11S1765. The sequence of the 5' flanking region does not contain a TATA
      element, but does contain several Sp1 binding sites, an AP-1 site and a novel
      inverted polymorphic GATA tandem repeat. This novel GATA repeat can be used for
      linkage analysis. The hsRPB7 gene seems to be highly conserved among eukaryotic
      species, showing general sequence conservation to yeast and Drosophila. Northern
      blot analysis reveals a high degree of tissue-specific expression. For example,
      adult retina, brain and kidney exhibit a relatively high level of expression. A
      moderate level of expression is observed in heart, lung, testis, cornea, retinal
      pigmented epithelium/choroid and placenta with a lower level of expression in the
      uterus, small intestine and skeletal muscle. A very low level of expression was
      observed in stomach and liver. Comparison between four fetal and adult tissues
      also demonstrate a surprising level of developmental specificity. Expression in
      fetal retina is considerably lower than fetal brain but similar to adult retina.

PMID- 9256065
TI  - The DNA-directed in vitro protein synthesizing system of Salmonella typhimurium:
      the effect of glutamate substitution.
AB  - The effect of potassium glutamate was examined on the DNA-directed in vitro
      protein synthesizing system of Salmonella typhimurium which conventionally
      contained acetate as a sole counter anion. The glutamate replacement increased
      the potassium optimum by about 70% and improved the expression of different DNA
      templates, but selectively. The biggest improvements in expression (about 8-fold)
      were seen with a lacUV5 (from Escherichia coli) template and with a mutant
      promoter his operon (from S. typhimurium) template. In contrast, the expression
      of a leuV promoter (from Escherichia coli) template was relatively unaffected by
      the glutamate replacement. The chain-growth-rate of mRNA and polypeptide
      syntheses in the DNA-directed in vitro protein synthesizing system were
      unaffected by the glutamate replacement. It was concluded that at least a part of
      the effect of glutamate replacement is on RNA polymerase-promoter interaction,
      and most likely the association step. Glutamate replacement did not alter the
      ppGpp-mediated positive and negative regulation of the his and leuV promoter,
      respectively, in the in vitro system. Taken together, the results suggest that
      the use of potassium glutamate in place of potassium acetate in DNA-directed in
      vitro synthesis provides a physiologically more relevant approximation of the
      ionic environment in vivo.

PMID- 9256064
TI  - Effects of bizelesin (U-77,779), a bifunctional alkylating minor groove binder,
      on replication of genomic and simian virus 40 DNA in BSC-1 cells.
AB  - Bizelesin, an AT-specific DNA-alkylating antitumor drug, is a potent inhibitor of
      genomic DNA replication in BSC-1 cells. Fifty percent inhibition of DNA synthesis
      was observed at 10 nM bizelesin compared to 160 nM needed for 50% inhibition of
      RNA synthesis while no inhibition of protein synthesis was observed up to 200 nM.
      Sedimentation analysis of nascent genomic DNA showed that bizelesin inhibited new
      replicon initiation and had significantly less effect on replicon maturation.
      Bizelesin also suppressed the intracellular synthesis of simian virus 40 (SV40)
      DNA in virus-infected BSC-1 cells. The analysis of nascent SV40 intermediates
      synthesized after bizelesin treatment confirmed an initiation-specific
      inhibition. The inhibitory effects on cellular DNA replication occurred at
      bizelesin levels resulting in infrequent adducts (one adduct per several
      replicons). Only one bizelesin adduct per several SV40 molecules was needed for a
      potent inhibition of intracellular SV40 replication. In contrast, only partial
      inhibition of SV40 replication in vitro was observed with bizelesin-treated naked
      SV40 DNA as a template. Overall, the results indicate that infrequent bizelesin
      lesions impede the cellular replication apparatus at the level of the initiation
      of new replicons.

PMID- 9256066
TI  - Differential regulation of the mitochondrial ADP/ATP translocase gene in wood
      frogs under freezing stress.
AB  - The gene Aat coding for ADP/ATP translocase (AAT) was cloned from liver of the
      freeze-tolerant wood frog, Rana sylvatica, via differential screening of a cDNA
      library from liver of frozen frogs and using probes from control versus frozen
      frogs. Sequence analysis showed that clone pBfFR07 bearing the AAT cDNA contained
      a 1318-bp insert with one full-length open reading frame. The deduced amino acid
      sequence included 317 residues, with 81-86% identities to mammalian AAT. A 1750
      nt transcript from the Aat gene was detected using pBfFR07 probe and a putative
      frog AAT of over 30 kDa was visualized by immunoblotting using a polyclonal
      antibody raised against chicken AAT. Analysis of liver samples from a time course
      of freezing showed a maximal 4.5-fold increase in mRNA after 8 h with AAT protein
      peaking in 24-h frozen frogs. Freezing also induced Aat expression in bladder and
      lung. In liver, mRNA expression also responded positively to anoxia stress but
      not to experimental dehydration of the animals. These results suggest that AAT
      induction during freezing may be stimulated by the ischemia that develops when
      plasma freezes; changes in AAT may contribute to stabilizing energetics in
      mitochondrial versus cytosolic pools over freeze/thaw cycles.

PMID- 9256067
TI  - In vivo effect of DNA relaxation on the transcription of gene rpoH in Escherichia
      coli.
AB  - The in vivo effect of Novobiocin, a gyrase inhibitor, on the transcription of
      gene rpoH which codes for sigma32, the main positive regulator of the heat-shock
      response, was studied. Novobiocin induced a three-fold increase and a slight
      decrease in the activity of the rpoH promoters P1 and P4, respectively. The
      Novobiocin-induced increase in the activity of promoter P1 correlates with an
      increase in the amount of proteins sigma32 and DnaK. These results suggest that
      the increase in expression of the heat-shock proteins induced by gyrase
      inhibitors is probably due to the increased activity of P1 on relaxed DNA.

PMID- 9256068
TI  - The dmsR gene encoding a dimethyl sulfoxide-responsive regulator for expression
      of dmsCBA (dimethyl sulfoxide respiration genes) in Rhodobacter sphaeroides f.
      sp. denitrificans.
AB  - Upstream of the dmsCBA genes encoding dimethyl sulfoxide (DMSO) reductase in the
      phototrophic bacterium Rhodobacter sphaeroides f. sp. denitrificans, there was
      found one gene (referred to dmsR) which encoded a protein composed of 232 amino
      acid residues and was divergently transcribed from the dmsCBA genes. The deduced
      amino acid sequence was homologous to the OmpR subfamily of response regulators
      in two-component systems for transcriptional regulation. The encoded protein DmsR
      was shown to bind to a DNA fragment containing the four direct repeats of a
      decameric nucleotide motif located between the dmsR and dmsCBA genes. The DNA
      binding activity of DmsR was observed when the organism was grown anaerobically
      in the presence of DMSO. A dmsR-defected mutant strain showed no synthesis of
      DMSO reductase. These results indicate that the dmsR gene product acts as a
      positive regulator for expression of the dmsCBA genes in response to DMSO under
      anaerobic growth conditions.

PMID- 9256069
TI  - Development and characterization of a binary gene expression system based on
      bacteriophage T7 components in adenovirus vectors.
AB  - To explore the utility of the bacteriophage T7 binary system in adenovirus (Ad)
      vectors we constructed three Ad5-based vectors containing the T7 RNA polymerase
      (T7pol) gene in either early region 1 (E1) or E3. The recombinant Ad vectors were
      either deficient (AdT7pol1, AdT7pol2) or competent (AdT7pol3) for replication in
      human cells other than Ad5 transformed (293) cells. To test the ability of the T7
      polymerase produced by these vectors to drive gene expression, a reporter vector
      was constructed with an E1 substitution comprising the bacterial beta
      galactosidase (betaGal) (lacZ) gene under the control of the T7 gene 10 promoter
      (T7pro) and linked to the encephalomyocarditis virus (EMCV) internal ribosome
      entry site (IRES) (AdBHG10T7betaGal). Coinfections were performed with the
      various AdT7pol vectors and the reporter vector, and expression was analysed in
      three different human cell lines: 293, A549 and MRC-5. Depending on the AdT7pol
      vector used, different levels of expression were obtained from the reporter gene.
      In 293 cells, expression was detected following infection at very low
      multiplicities of infection (moi) with all of the T7pol vectors when coinfected
      with the reporter vector AdBHG10T7betaGal. In A549 and MRC-5 cells very little
      expression was detected using AdT7pol1 or pol2 and efficient expression was only
      obtained when relatively high moi values of the replication-competent vector were
      used in the coinfections. We also constructed a single vector containing both
      elements of the T7 system (T7pol in E3 and T7 promoter driving expression of the
      chloramphenicol acetyl transferase (cat) gene in E1). This vector proved
      difficult to rescue but was stable once isolated. Finally, experiments performed
      to evaluate the 'leakiness' of the Ad-T7 system detected very little expression
      from the T7pro in the absence of T7 polymerase suggesting this system may be
      useful for the cloning and expression of genes encoding cytotoxic proteins.

PMID- 9256070
TI  - Molecular cloning of a rod opsin cDNA from the skate retina.
AB  - Skates (Raja erinacea and R. ocellata) are among the few animals that have an
      exclusively rod retina. However, skate rods are unusual in that they are capable
      of adapting to extremely high levels of illumination that initially saturate the
      rod photocurrent. This adaptive process restores the ability of the visual cells
      to respond to incremental photic stimuli and enables them to function under
      ambient conditions that are subserved by the cone mechanism in mixed (rod/cone)
      retinae. As a first step towards exploring the molecular basis of visual
      adaptation in the skate retina, we have cloned and analyzed the opsin cDNA from a
      skate retina library. The cDNA codes for a protein 354 amino acids (aa) long and
      39.7 kDa predicted molecular mass, and labels a single abundant transcript of 1.7
      kb in retinal RNA. Amino acid alignments and a parsimony analysis of nucleotide
      alignments show the skate opsin to be homologous to other rod opsins. An analysis
      of the aa sequence reveals a high degree of conservation of those residues
      thought to be important for most aspects of rhodopsin function. However, a few
      critical aa replacements may indicate alterations in the interactions of skate
      rhodopsin with other proteins in the phototransduction cascade. In particular,
      replacements of Glu150 with serine and Cys323 with leucine are in cytoplasmic
      domains thought to interact with transducin and rhodopsin kinase. The latter
      change eliminates one of the conserved acylation sites in the carboxyl terminal
      tail. These substitutions increase the similarity of the cytoplasmic domains of
      skate opsin to those of blue-sensitive visual pigments.

PMID- 9256071
TI  - Isolation and characterisation of a novel stress-inducible PDI-family gene from
      Aspergillus niger.
AB  - Current strategies to improve the secretion of heterologous proteins in
      Aspergillus niger include the manipulation of chaperones and foldases specific to
      the endoplasmic reticulum (ER). A family of ER-specific proteins which share
      active-site homology wit protein disulfide isomerase (PDI) has been identified
      from other systems, many of which are inducible by agents which cause malfolding
      of proteins in the ER. Here we report identification of tigA from Aspergillus
      niger and erp38 from Neurospora crassa, two novel members of the PDI superfamily
      of proteins. TIGA and ERp38 show 66% identity at the amino acid level and are
      putative ER proteins. Both proteins show tandemly linked thiol-oxidoreductase
      domains followed by a functionally uncharacterised C-terminal domain. The most
      distal active site in TIGA is created by excision of a 66-bp intron. Although no
      Unfolded Protein Response elements can be seen in the tigA promoter, sequence
      homology has identified associated with protein trafficking (ERPTRE) in a gene
      encoding the related mammalian protein, ERp72, as well as a second motif
      conserved amongst the glucose-related protein family. Southern and dot blot
      analysis indicate that the tigA gene is present in single copy. Both the A. niger
      and N. crassa proteins show homology with a stress-inducible alfalfa, G1.
      Transcription of tigA is induced 2-3-fold after treatment with tunicamycin, an
      inhibitor of N-linked glycosylation. Strains overexpressing a heterologous
      protein show no increased tigA mRNA levels.

PMID- 9256072
TI  - Human type II arginase: sequence analysis and tissue-specific expression.
AB  - A full-length cDNA encoding type II arginase was isolated from a human kidney
      cDNA library and its sequence compared to those of vertebrate type I arginases as
      well as to arginases of bacteria, fungi and plants. The predicted sequence of
      human type II arginase is 58% identical to the sequence of human type I arginase
      but is 71% identical to the sequence of Xenopus type II arginase, suggesting that
      duplication of the arginase gene occurred before mammals and amphibians diverged.
      Seven residues known to be essential for activity were found to be conserved in
      all arginases. Type II arginase mRNA was detected in virtually all human and
      mouse RNA samples tested whereas type I arginase mRNA was found only in liver. At
      least five mRNA species hybridizing to type II arginase cDNA were found in the
      human RNA samples whereas only a single type II arginase mRNA species was found
      in the mouse. This raises the possibility that the multiple type II arginase
      mRNAs in humans arise from differential RNA processing or usage of alternative
      promoters.

PMID- 9256073
TI  - Molecular characterization of the C-3 DNA puff gene of Rhynchosciara americana.
AB  - We have mapped a region of about 33 kb which includes the transcription unit of
      the C-3 DNA puff gene of Rhynchosciara americana. The C-3 TU and a region
      extending approximately 800 bp upstream of the C-3 promoter were characterized.
      The TU is composed of three exons and produces a 1.1-kb mRNA whose level in
      salivary glands increases with the expansion of the C-3 puff. The C-3 messenger
      appears to undergo rapid deadenylation resulting in an RNA of about 0.95 kb which
      can still be observed in gland cells 15 h after the puff has regressed. The 1.1
      kb mRNA codes for a 32.4-kDa, predominantly alpha-helical polypeptide with three
      conserved parallel coiled-coil stretches. The aa composition and structure of
      this polypeptide suggests that it is secreted and contributes to the formation of
      the cocoon in which the larvae pupate. The region upstream of the promoter
      contains several A-rich sequences with similarity to the ACS of yeast which might
      have a role in the initiation of replication/amplification.

PMID- 9256074
TI  - Cloning, structural analysis and expression of the gene encoding Hsp32 from
      Dictyostelium discoideum.
AB  - We have isolated and characterized genomic clones encoding a novel small heat
      shock (HS) protein (Hsp32) from Dictyostelium discoideum that is not homologous
      to the alpha-crystallin family Hsps. Besides its induction by HS, this gene is
      also regulated during the life cycle of the organism. At physiologic temperatures
      hsp32 is expressed at high levels in growing cells and at low levels in cells
      starved to initiate their developmental programme. However, in both cases the
      gene can be induced by HS. A DNA fragment containing the upstream region of hsp32
      was shown to confer HS induction to a cat reporter gene, indicating a
      transcriptional regulation for this gene. A single transcription start site,
      located at position -152 relative to the initiator Met, 17 nucleotides downstream
      from a putative TATA box, was determined both in vegetative cells and cells
      starved for 6 h. This site was unchanged when either vegetative or starved cells
      were submitted to HS at 30 degrees C for 30 min. Despite HS induction, a perfect
      HSE element was not found in the 5' regulatory region of the gene. The hsp32
      coding region is interrupted by a single intron located near its 5' end, which is
      properly spliced even under HS conditions.

PMID- 9256075
TI  - Conservation of the Caenorhabditis elegans cuticle collagen gene col-12 in
      Caenorhabditis briggsae.
AB  - The functional importance of the majority of Caenorhabditis elegans cuticle
      collagen genes is unknown. We have identified, cloned and sequenced the
      Caenorhabditis briggsae homologue of the C. elegans gene col-12, a cuticle
      collagen for which no mutants have yet been identified. Homology in the flanking
      sequence has allowed us to unambiguously identify this gene as the col-12
      homologue, as opposed to some other closely related member of this large
      multigene family. The whole of the predicted polypeptide is highly conserved
      (94.9% identical), including those regions not yet shown by mutational analysis
      to be important for C. elegans cuticle collagen function. These include the whole
      of the N-terminal non-Gly-X-Y domain and the X and Y positions of the Gly-X-Y
      domain. This may be a consequence of the requirement of cuticle collagens to
      participate in intermolecular interactions throughout the full length of the
      polypeptide. There is increasing evidence to suggest that conservation between C.
      elegans and C. briggsae is confined to functionally significant sequence. Hence,
      the conservation of col-12 between these two species provides evidence that this
      member of the cuticle collagen family has a significant structural function.

PMID- 9256077
TI  - Recent polymorphic insertion of an Alu repeat in the baboon lipoprotein lipase
      (LPL) gene.
AB  - We have identified a polymorphic insertion in the lipoprotein lipase (LPL) gene
      in a captive baboon colony. Mapping and nucleotide (nt) sequence analysis of the
      polymorphism showed that it is due to the presence or absence of an Alu
      repetitive element in intron 7 of the baboon LPL gene. This polymorphic Alu
      repeat has not been reported in humans, and we did not detect the repeat in a
      survey of the LPL intron 7 gene region in other non-human primates. Comparison of
      nt at diagnostic positions in this Alu insertion with different Alu subfamily
      consensus sequences showed that it most closely resembles the young AluY
      subfamily. These data suggest that this polymorphic Alu repeat inserted
      independently in the baboon lineage.

PMID- 9256076
TI  - Conserved features of selenocysteine insertion sequence (SECIS) elements in
      selenoprotein W cDNAs from five species.
AB  - SECIS elements form stem-loop structures in the 3' untranslated regions (UTR) of
      eukaryotic mRNAs that encode selenoproteins. These elements direct incorporation
      of selenocysteine at UGA codons, provided the SECIS element lies a sufficient
      distance from the UGA. The cDNAs encoding skeletal muscle selenoprotein W from
      human, rhesus monkey, sheep, rat, and mouse contained highly similar SECIS
      elements that retained important features common to all known SECIS elements.
      Comparative analysis of these SECIS elements showed that in some regions both
      predicted secondary structure and nucleotide sequences were conserved, in other
      areas secondary structure was maintained using different primary sequence, and in
      still other portions, base pairing was not conserved. The rodent and sheep
      selenoprotein W mRNAs used UGA as a stop codon and as a selenocysteine codon.
      Thus, UGA specified both selenocysteine incorporation and termination in a single
      mRNA. The selenoprotein W SECIS elements contained an additional highly conserved
      base-paired stem that may prevent inappropriate selenocysteine incorporation at
      the UGA stop codons.

PMID- 9256078
TI  - Cloning and characterization of the S. pombe gene efc25+, a new putative guanine
      nucleotide exchange factor.
AB  - We report the cloning and characterization of a new S. pombe gene, efc25+, for
      'exchange factor Cdc25-like'. The C-terminal region of the predicted product of
      this gene displays high sequence homology with a number of guanine nucleotide
      exchange factors for Ras. These include Cdc25 of Saccharomyces cerevisiae, Cdc25
      of Saccharomyces kluyveri, Csc25 of Candida albicans, Sdc25 of S. cerevisiae and
      Ste6 of Schizosaccharomyces pombe. Disruption of efc25+ resulted in cells with a
      spherical shape reminiscent of the abnormal morphological phenotype of ras1
      deletion mutants. However, unlike ras1 null mutants, strains deleted for efc25+
      were proficient for mating and sporulation. This differs from the only other Ras1
      exchange factor characterized so far in S. pombe, the Ste6 protein, whose
      deletion results in defects in mating and sporulation but not in cell shape. We
      hypothesize that Efc25 is an exchange factor for Ras1 and that it is involved in
      a signaling pathway different from that involving Ste6.

PMID- 9256079
TI  - A novel member of an ancient superfamily: sponge (Geodia cydonium, Porifera)
      putative protein that features scavenger receptor cysteine-rich repeats.
AB  - Proteins featuring scavenger receptor cysteine-rich (SRCR) domains are prominent
      receptors known from vertebrates and from one phylum of invertebrates, the
      echinoderms. In the present study we report the first putative SRCR protein from
      the marine sponge Geodia cydonium (Porifera), a member of the lowest phylum of
      contemporary Metazoans. Two forms of SRCR molecules were characterized, which
      apparently represent alternative splicing of the same transcript. The long
      putative SRCR protein, of 1536 aa, features twelve SRCR repeats, a C-terminal
      transmembrane domain and a cytoplasmic tail. The sequence of the short form is
      identical with the long form except that it lacks a coding region near the C
      terminus, thus the 1195 aa deduced protein consists of only the first ten SRCR
      domains and the last 26 C-terminal aa residues, without the transmembrane domain.
      Homology searches revealed that the sponge putative SRCR protein shares with
      bovine T-cell antigen WC1 29.2% identity in 1054 aa overlap, 33.9% identity in
      475 aa overlap with sea urchin speract and 56% identity in 110 aa overlap with
      macrophage scavenger receptor type I. Based upon the number and location of the
      conserved Cys residues, the sponge SRCR domain repeats were classified as
      belonging to group A of the SRCR superfamily. With twelve SRCR repeats, one more
      than those in any of the previously described SRCR proteins, and several membrane
      bound and soluble forms, it seems that the most primitive known member of this
      family may be the structurally most complex one among SRCR containing proteins.

PMID- 9256081
TI  - High-level production and purification of biologically active proteins from
      bacterial and mammalian cells using the tandem pGFLEX expression system.
AB  - Because of the complexities involved in the regulation of gene expression in
      Escherichia coli and mammalian cells, it is considered general practice to use
      different vectors for heterologous expression of recombinant proteins in these
      host systems. However, we have developed and report a shuttle vector system,
      pGFLEX, that provides high-level expression of recombinant glutathione S
      transferase (GST) fusion proteins in E. coli and mammalian cells. pGFLEX contains
      the cytomegaloma virus (CMV) immediate-early promoter in tandem with the E. coli
      lacZpo system. The sequences involved in gene expression have been appropriately
      modified to enable high-level production of fusion proteins in either cell type.
      The pGFLEX expression system allows production of target proteins fused to either
      the N or C terminus of the GST pi protein and provides rapid purification of
      target proteins as either GST fusions or native proteins after cleavage with
      thrombin. The utility of this vector in identifying and purifying a component of
      a multi-protein complex is demonstrated with cyclin A. The pGFLEX expression
      system provides a singular and widely applicable tool for laboratory or
      industrial production of biologically active recombinant proteins in E. coli and
      mammalian cells.

PMID- 9256080
TI  - The bovine guanylate cyclase GC-E gene and 5' flanking region.
AB  - The gene encoding the bovine guanylate cyclase isoform E (GC-E) was isolated as a
      single 18 kb genomic clone and shown to have 20 exons and 19 introns. Comparison
      of the structure of the GC-E gene with structures of other membrane guanylate
      cyclase genes indicates that the GC-E is most closely related to the subfamily of
      sensory guanylate cyclases. Comparison of the GC-E structure with that of the
      more distantly related guanylate cyclase isoform A (GC-A) gene shows the most
      divergence in the extracellular and C-terminal regions, but general conservation
      of introns and exons in the intracellular kinase-like and catalytic domains. RT
      PCR from several bovine tissues shows that GC-E is expressed only in the retina.
      Consistent with this pattern of expression, elements for the retinal-specific
      transcription factors RET-1, RET-2 and Talpha-1 are located in the 5' flanking
      promoter region.

PMID- 9256082
TI  - Intronic sequences modulate the sensitivity of beta-lactoglobulin transgenes to
      position effects.
AB  - We have analysed the expression of beta-lactoglobulin (BLG) gene constructs with
      combinations of introns deleted to further define the role of intronic regions in
      directing position-independent mammary expression of BLG transgenes. Intron
      removal had no obvious effect on hormonal induction of BLG expression in vitro
      but dramatically reduced expression in vivo, in that removal of intron pairs
      always resulted in a proportion of the transgenic lines generated failing to
      express the transgene in the mammary gland. Position-dependent expression was
      seen for all intron-deleted transgenes regardless of which introns were removed
      and the ability of the intron-deleted transgenes to be expressed bore no
      relationship to transgene copy number. Thus, intron removal per se increases the
      sensitivity of BLG transgenes to position effects.

PMID- 9256083
TI  - Identification of a human heart FABP pseudogene located on chromosome 13.
AB  - The fatty acid-binding proteins (FABPs) constitute a conserved group of cytosolic
      low molecular mass proteins, which consists of several types: liver, heart,
      myelin, epidermal, adipocyte, brain, intestinal and ileal type. The FABP gene
      structure is well conserved during evolution and exhibits a four-exon/three
      intron structure. In the past, multiple hybridizing fragments were detected upon
      Southern blot analysis using heart FABP (H-FABP) cDNA as a probe. The origin of
      these fragments was not clear. We screened a human genomic library and isolated
      an intronless gene (FABP3-ps) with 85% similarity to the human H-FABP cDNA and
      high similarity (76 and 79%) to the H-FABP cDNAs of mouse and bovine,
      respectively. By means of fluorescence in situ hybridization this processed
      pseudogene could be assigned chromosome 13q13-q14, whereas the gene for human H
      FABP (FABP3) resides on chromosome 1p32-p33. No expression of the processed
      pseudogene could be detected in skeletal muscle or fetal brain.

PMID- 9256084
TI  - Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell
      phenotype.
AB  - Nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) have been
      reported to prevent vascular smooth muscle cell (VSMC) proliferation and have
      beneficial effects to reduce intimal thickening in response to arterial injury.
      The purpose of this study was to determine whether the downstream effector
      molecule of NO-cGMP signaling, cyclic GMP-dependent protein kinase (PKG),
      regulates phenotypic modulation and proliferation in cultured rat aortic VSMC.
      PKG-expressing VSMC lines were created by transfection of PKG-deficient cell
      lines and characterized. All forms of PKG, i.e. PKG-I alpha and PKG-I beta, as
      well as the constitutively active catalytic domain of PKG-I, transformed
      dedifferentiated 'synthetic' VSMC to a more contractile-like morphology. PKG
      expression resulted in an increased production of the contractile phenotype
      marker proteins, smooth muscle myosin heavy chain-2, calponin and alpha-actin and
      restored the capacity of cAMP and cGMP analogues to inhibit platelet-derived
      growth factor (PDGF)-induced cell migration. On the other hand, PKG expression
      had no significant effects on PDGF-induced cell proliferation. These results
      suggest that PKG expression contributes to the regulation of a contractile-like
      phenotypic expression in cultured VSMC, and the suppression of PKG expression
      during cultured growth in vitro may permit the modulation of cells to a more
      synthetic, dedifferentiated phenotype.

PMID- 9256085
TI  - The influence of lesion length on intimal hyperplasia after Fogarty balloon
      injury in the rabbit carotid artery: role of endothelium.
AB  - After balloon angioplasty, retarded endothelial cell recoverage of the injured
      segment may lead to enhanced intimal hyperplasia. We tested the hypothesis that
      long lesions result in more intimal hyperplasia than short lesions due to a
      prolonged time to complete endothelial cell recoverage. A 2-french Fogarty
      balloon was used to create 2.5- and 5-cm-long lesions in the rabbit carotid
      artery. After termination, the injured arteries (n = 9 for all groups) were
      serially processed for histochemistry. Endothelial cell coverage was assessed
      with an antibody to CD31 and cell proliferation with a monoclonal antibody to Ki
      67 nuclear antigen. The intimal hyperplasia cross-sectional area was measured
      morphometrically. All data are mean +/- SEM. At 21 days, endothelial cell
      recoverage was almost complete in the 2.5-cm lesions. In the 5-cm lesions,
      endothelial cell recoverage was 66 +/- 6% in the middle segments (p = 0.04, 2.5
      vs. 5 cm) and 100% at the cranial and caudal ends of the lesion. At 42 days,
      endothelial cell coverage had increased to 81 +/- 7% in the middle segments of
      the 5-cm lesions. The intimal hyperplasia area was similar in the 2.5- and the 5
      cm lesions both at 21 days (0.19 +/- 0.02 and 0.20 +/- 0.01 mm2, respectively)
      and 42 days (0.27 +/- 0.02 and 0.26 +/- 0.03 mm2, respectively). The increase in
      intimal hyperplasia from 21 to 42 days was significant for both lesion lengths (p
      = 0.004). At 21 days, intimal proliferation was similar for the 2.5- and 5-cm
      lesions. After 42 days postinjury, intimal proliferation had decreased (p <
      0.001) equally for both lesion lengths. Earlier recoverage by endothelium in the
      2.5-cm lesions did not inhibit intimal hyperplasia compared to the 5-cm lesions
      which were still incompletely reendothelialized. We conclude that in the rabbit,
      rapid endothelial cell recoverage of Fogarty balloon-injured arteries may not
      limit intimal hyperplasia in the center of the lesion. It is conceivable that the
      inability of regenerated endothelium to inhibit intimal hyperplasia is due to its
      initially dedifferentiated and possibly dysfunctional phenotype.

PMID- 9256086
TI  - Vascular effects of proteinase-activated receptor 2 agonist peptide.
AB  - Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor related
      to the thrombin receptor. PAR-2 can be activated by trypsin and by synthetic
      peptides corresponding to the new amino terminus generated by activating
      proteolytic cleavage. We show in this report that intravenous injection of PAR-2
      agonist peptides has dramatic effects on arterial blood pressure in anesthetized
      rats. The peptide SLIGRLETQPPI, at 150 nmol/kg, transiently decreased the mean
      arterial pressure from 104 to 60 mm Hg. The hypotensive response was dose
      dependent, and was not secondary to effects on central vasoregulatory systems,
      heart rate, or the kidneys. A nitric oxide synthase inhibitor attenuated the
      hypotensive response induced by the PAR-2 agonist peptide. Further experiments in
      vitro, on preparations of rat femoral artery and vein, showed that PAR-2 agonist
      peptide elicited a dose-dependent relaxation of both types of vessel. Removal of
      the endothelium abolished the agonist peptide-induced relaxation. Our results
      demonstrate that activation of PAR-2 can modulate vascular tone, and that this
      response was an effect mediated at least partly by nitric oxide. The effect on
      blood vessels further suggests that the physiological activator of this
      proteolytically activated receptor is an enzyme present and active in the blood,
      possibly after a vascular injury.

PMID- 9256087
TI  - Regulation of the fibrinolytic potential of cultured human umbilical vein
      endothelial cells: astragaloside IV downregulates plasminogen activator inhibitor
      1 and upregulates tissue-type plasminogen activator expression.
AB  - We have investigated whether the saponin astragaloside IV (AS-IV), a 3-O-beta-D
      xylopyranosyl-6-O-beta-D-glucopyranosylcycloastragenol, purified from the Chinese
      herb drug Astragalus membranaceus, which is used in traditional Chinese medicine
      to treat cardiovascular diseases, might affect the fibrinolytic potential of
      cultured human umbilical vein endothelial cells (HUVECs). When HUVECs were
      conditioned with AS-IV, a dose (0.01-100 microg AS-IV/ml)- and time-dependent
      decrease in plasminogen activator inhibitor type 1 (PAI-1) and an increase in
      tissue-type plasminogen activator (t-PA) synthesis were observed, which were
      significant from 1 microg AS-IV/ml and from 12 h of incubation with 100 microg AS
      IV/ml. PAI-1 antigen decreased from 641 +/- 86 to 318 +/- 18 ng/10(5) cells/24 h,
      whereas t-PA antigen increased from 4.1 +/- 0.3 to 9.7 +/- 0.4 ng/10(5) cells/24
      h after addition of 100 microg AS-IV/ml. PAI-1 activity decreased to 30% of
      control level, whereas t-PA activity and t-PA-PAI-1 complexes reached a maximum
      stimulation of 3- and 5-fold over control levels, respectively, in the
      conditioned media of HUVECs treated with 100 microg AS-IV/ml for 24 h. PAI-1
      specific mRNA expression decreased to 55% (2.2 kb) and 72% (3.2 kb), 66% (2.2 kb)
      and 88% (3.2 kb), and 19% (2.2 kb) and 41% (3.2 kb) of control values after
      incubation for 6, 12 and 18 h, respectively, whereas t-PA-specific mRNA increased
      2-, 2.5- and 1.4-fold in HUVECs treated with 100 microg/ml AS-IV for 6, 12, and
      18 h, respectively. In conclusion our data give evidence that in fact AS-IV can
      increase the fibrinolytic potential of cultured HUVECs not only by upregulating
      the expression of t-PA as NG-R1 does, but also by downregulating the expression
      of PAI-1.

PMID- 9256088
TI  - Estrogen does not induce the calcium-dependent nitric oxide synthase in cultured
      human uterine endothelial and myometrial smooth muscle cells.
AB  - In many tissues, estrogen-induced vasodilatation is mediated, at least in part,
      by the release of nitric oxide (NO). We determined whether human myometrial
      endothelial and smooth muscle cells express estrogen receptors (ERs) and whether
      endothelial NO synthase (eNOS) expression in these cells was affected by 17beta
      estradiol (10[-13]-10[-6]M). ER was strongly expressed in myometrial smooth
      muscle cells but was absent from endothelial cells. Expression of eNOS mRNA was
      strong in endothelial cells, but weak in muscle cells. 17beta-estradiol
      administration for 24 or 72 h failed to increase eNOS in both cell types. Thus,
      an increase of human uterine blood flow by estrogens appears not to be mediated
      by stimulation of myometrial eNOS expression.

PMID- 9256089
TI  - Angiotensin II induces media hypertrophy and hyperreactivity in mesenteric but
      not epigastric small arteries of the rat.
AB  - We examined effects of a 2-week infusion of angiotensin II (AII, 250 ng x kg[-1]
      x min[-1]) on properties of mesenteric resistance arteries (MrA) and superior
      epigastric arteries (SEA) of male Wistar rats. Histochemistry and pharmacological
      tools showed that MrA are densely innervated, whereas SEA are only sparsely
      innervated. AII infusion resulted in a significant elevation in mean arterial
      pressure and in plasma AII and noradrenaline levels. Organ chamber studies and
      morphometry were used to determine arterial contractile reactivity and structure.
      After AII infusion, in MrA (i) maximal contractile responses to 125 mM K+,
      noradrenaline, serotonin and adrenergic nerve stimulation were significantly
      increased, without modification of the sensitivity to these stimuli and (ii) a
      significant increase in media cross-sectional area and media thickness was
      observed without alterations in lumen diameter. The observed increase in vascular
      reactivity could fully be attributed to the observed increase in wall mass since
      no alterations in maximal active wall stress were noted. In SEA, no significant
      changes in responsiveness to vasoconstrictor stimuli or in wall structure were
      observed. These findings suggest that perivascular nerves are involved in the
      hypertrophy and subsequent hyperreactivity of small arteries in rats exposed for
      2 weeks to a low dose of AII.

PMID- 9256090
TI  - The wall to lumen ratio of the radial artery in patients with Raynaud's
      phenomenon.
AB  - The pathophysiology of Raynaud's phenomenon (RP) remains an enigma. Whatever
      theories proposed, the final event leading to the clinical symptoms is the
      occlusion of digital vessels. However, the possibility that the upstream large
      arterial vessels contribute to vasopasm has never been investigated. We used a
      high resolution echo-tracking device to calculate lumen diameter, wall thickness,
      and circumferential wall stress upstream the digital arteries, i.e. at the site
      of the radial artery. Fifteen control women, 15 age-matched women with primary RP
      (PRP) and 15 women presenting with a secondary RP due to systemic sclerosis (SSc)
      were included in the study. All vasodilating agents were discontinued 72 h before
      the study session, which was conducted in a room with a stable ambient
      temperature of 22 degrees C. Radial artery internal diameter, intima-media wall
      thickness, and mean arterial pressure were measured simultaneously. Internal
      diameter of patients with RP was significantly decreased (p < 0.001 vs. controls)
      whereas intima-media wall thickness and mean arterial pressure were closely
      similar in the three groups, resulting in an increase in the wall to lumen ratio.
      Thus, circumferential wall stress was significantly smaller (p < 0.05 vs.
      controls) in patients with RP. In conclusion, this study demonstrates that in
      patients with RP, wall to lumen ratio is increased and circumferential wall
      stress is reduced at the level of the radial artery. It is suggested that the
      geometrical and mechanical changes of this artery may favor the downstream
      occlusive phenomena observed in patients with PRP and SSc.

PMID- 9256091
TI  - Combined physical therapy for lymphedema evaluated by fluorescence
      microlymphography and lymph capillary pressure measurements.
AB  - The treatment of patients with lymphedema is still controversial. Combined
      physical therapy with manual lymph drainage and compression therapy is most
      frequently used to reduce lymphatic leg swelling. However, objective evidence is
      rare that this empirical form of treatment has a scientific basis. In a
      prospective study fluorescence microlymphography and pressure measurements in
      cutaneous lymph capillaries were used to assess objectively the effect of
      combined decongestive physical therapy on abnormal microlymphatic dynamics in
      lymphedema. 12 patients with primary and secondary lymphedema were studied before
      treatment, after 2 weeks of intensive physical therapy and 3 months of continuing
      compression and ergotherapy. After 2 weeks of intensive manual lymph drainage and
      compression bandaging (phase 1) microlymphatic hypertension (12.8 +/- 5.7 mm Hg)
      was significantly (p = 0.01) reduced to a mean lymph capillary pressure of 5.9 +/
      4.5 mm Hg. More than 3 months later after continuing compression lymph capillary
      pressure (3.2 +/- 5.2 mm Hg) was still significantly (p = 0.03) reduced.
      Simultaneously the maximum spread of the fluorescent contrast medium in the
      superficial lymph capillary network decreased significantly (p = 0.01) from 21.3
      +/- 14.3 to 11.3 +/- 4.8 mm. Accordingly the clinical condition improved, and the
      mean circumferences of the forefoot and ankle were significantly (p < 0.05)
      reduced. Combined decongestive physical therapy is an effective treatment for
      lymphedema which results in a normalization of microlymphatic hypertension and an
      improvement of the clinical appearance.

PMID- 9256092
TI  - Influence of hypoxia/ischemia on cerebrovascular responses to oxytocin in
      piglets.
AB  - We examined the effects of hypoxic/ischemic stress on cerebral arteriolar
      responses to oxytocin in anesthetized piglets. Pial arteriolar diameters were
      measured using a cranial window and intravital microscopy. First, we evaluated
      arteriolar responses to topical application of oxytocin during normoxic
      conditions. We then determined whether 5-10 min of arterial hypoxia, ischemia, or
      asphyxia alters oxytocin-induced responses. Arterial hypoxia was produced by
      inhalation of 7.5% O2-92.5% N2 for 10 min. Ischemia was achieved by increasing
      intracranial pressure for 10 min. Asphyxia was achieved by turning off the
      ventilator for 5 min. During normoxic conditions, oxytocin dilated pial
      arterioles by 9 +/- 1% at 10(-8) and by 16 +/- 1% at 10(-6) mol/l (n = 47, p <
      0.05). Arteriolar responses to oxytocin did not change with repeated applications
      (n = 10). Following hypoxia, dilator effect of oxytocin was not changed at 10(-8)
      (8 +/- 2%) but it was reduced at 10(-6) mol/l (7 +/- 2%; p < 0.05, n = 8). After
      asphyxia or ischemia, oxytocin did not dilate arterioles at 10(-8) mol/l, whereas
      10(-6) mol/l resulted in a mild vasoconstriction (-4 +/- 3 to -6 +/- 4%, n = 6
      and 8). Topically applied superoxide dismutase did not preserve arteriolar
      responses to oxytocin after asphyxia although the arterioles did not constrict to
      10(-6) mol/l oxytocin (n = 5). Dilatation of cerebral arterioles in response to
      oxytocin was reversed to constriction by N(omega)-nitro-L-arginine methyl ester
      (L-NAME) (15 mg/kg, i.v.; n = 5) and by endothelial impairment by intra-arterial
      infusion of phorbol ester (10[-5] mol/l; n = 5). We conclude that the absence of
      pial arteriolar dilation to oxytocin after ischemia and asphyxia indicates
      endothelial dysfunction which may be involved in the pathology of perinatal brain
      injury.

PMID- 9256093
TI  - Is the phenotypic change in vascular smooth muscle cells a prerequisite for the
      efficacy of environmental cues as inducers of arterial wall lesions?

PMID- 9256094
TI  - A new method for absolute quantitation of MRS metabolites.
AB  - A new method for absolute quantitation of MRS spectra is presented. This method
      is not based on a reference peak, derived from a real NMR signal, but rather on a
      synthesized NMR reference produced by an electronic device, transmitted by a
      broad-band antenna to avoid quality factor variations. This signal is therefore
      received at the same time as the sample signal. The reference line produced is
      stable in time (maximum variation lower than 2%) and allows precise and accurate
      measurement of absolute concentrations (mean error lower than 3%) in vitro and in
      vivo.

PMID- 9256095
TI  - The functional scout image: immediate mapping of cortical function at 4 Tesla
      using receiver phase cycling.
AB  - A rapid method of generating functional scout images to map cortical activity is
      presented. Maps were produced immediately "on-line" on the scanner's console
      using fast low-angle shot gradient-recalled echo and echo-planar imaging
      sequences without special hardware. To demonstrate the technique, raw data
      collected during photic stimulation and dark control periods were subtracted
      through phase alternation of the receiver with constant transmitted radio
      frequency phase. A blood oxygen level-dependent signal difference map was
      produced by magnitude reconstruction of the resulting complex-difference data.
      Maps improved in contrast with an increasing number of stimulation-control cycles
      and showed similar areas of activation to traditional fMRI processing methods.
      Such a functional scout procedure allows rapid localization of brain function
      within the anatomical region of interest. From these functional scout images,
      slices or voxels may be planned by using the scanner manufacturers prescription
      tools for further specialized studies.

PMID- 9256096
TI  - The effect of magnetization transfer on functional MRI signals.
AB  - A magnetization transfer (MT)-prepared echo-planar imaging (EPI) pulse sequence
      was developed to study motor cortex activation, using a finger tapping paradigm.
      MT weighting resulted in a reduction of both the activated area and, in the
      majority of activated pixels, the functional MRI signal, regardless of the
      correlation coefficient threshold used in generating the activation map. The
      magnetization transfer ratio (MTR) was higher during task activation than during
      rest. Because the MT effect is strongly tissue-dependent, these results support
      the hypothesis that incorporation of MT into functional MRI will help to
      understand the origin of the functional MRI signal.

PMID- 9256097
TI  - Determination of deoxymyoglobin changes during graded myocardial ischemia: an in
      vivo 1H NMR spectroscopy study.
AB  - 1H NMR spectroscopy was used to detect the proximal histidyl Ndelta proton signal
      of deoxymyoglobin from canine hearts in vivo during graded myocardial ischemia.
      The NMR signal intensity provided an indicator of intracellular oxygenation in
      myocardium. The relationship between the myocardial blood flow and the
      deoxymyoglobin concentration was successfully measured during resting, partial,
      and complete coronary artery occlusion conditions. The results demonstrate the
      feasibility to detect deoxymyoglobin using a 1H NMR spectroscopy technique in
      living hearts for the first time and the possibility to use this technique for
      investigating myocardial oxidative metabolism nondestructively and repetitively.

PMID- 9256098
TI  - Consistent fat suppression with compensated spectral-spatial pulses.
AB  - Reliable fat suppression is especially important with fast imaging techniques
      such as echo-planar (EPI), spiral, and fast spin-echo (FSE) T2-weighted imaging.
      Spectral-spatial excitation has a number of advantages over spectrally selective
      presaturation techniques, including better resilience to B0 and B1 inhomogeneity.
      In this paper, a FSE sequence using a spectral-spatial excitation pulse for
      superior fat suppression is presented. Previous problems maintaining the CPMG
      condition are solved using simple methods to accurately program radio-frequency
      (RF) phase. Next an analysis shows how B0 eddy currents can reduce fat
      suppression effectiveness for spectral-spatial pulses designed for conventional
      gradient systems. Three methods to compensate for the degradation are provided.
      Both the causes of the degradation and the compensation techniques apply equally
      to gradient-recalled applications using these pulses. These problems do not apply
      to pulses designed for high-speed gradient systems. The spectral-spatial FSE
      sequence delivers clinically lower fat signal with better uniformity than
      spectrally selective pre-saturation techniques.

PMID- 9256099
TI  - In vivo sodium multiple quantum spectroscopy of human articular cartilage.
AB  - The authors report, for the first time, sodium properties of human articular
      cartilage in vivo using sodium multiple-quantum-filtered methods with a surface
      coil. A flip angle-independent, phase-cycled pulse sequence was used to obtain
      triple-quantum-filtered spectra as a function of preparation time. Biexponential
      relaxation rates were calculated by fitting the triple-quantum-filtered spectral
      amplitudes to a theoretical expression. Theoretical analysis of the flip angle
      dependence of even rank two-quantum coherence (T2[2]), odd rank two-quantum
      coherence (T2[3]), and triple-quantum coherence are presented and verified
      against experimental results on a cartilage specimen. Sodium multiple-quantum
      filtered spectral lineshapes obtained in vivo correlate well with those observed
      on in vitro specimens. Relaxation rates obtained from asymptomatic volunteers
      were found to be: T(2rise) = 1.0 + 0.12 ms, T(2decay) = 12.0 +/- 0.75 ms (mean +/
      SD). The diagnostic potential of this method in detecting early changes in
      articular cartilage is described.

PMID- 9256100
TI  - In vivo validation of MR pulse pressure measurement in an aortic flow model:
      preliminary results.
AB  - MR imaging experiments were conducted to investigate the feasibility of
      estimating vascular pulse pressure waveforms from measurements of blood flow
      rates and vessel cross-sectional area. Blood flow waveforms were measured in the
      aorta's of three 25-30-kg pigs at multiple imaging sections using phase-contrast
      velocity imaging. Estimates of pulse pressure were derived from these data by
      evaluating a model characterizing the relationship between pressure, flow, and
      the cross-sectional area of a vessel segment. Comparisons between the MR-derived
      estimates of pressure and those obtained from a micromanometer pressure catheter
      indicate that accurate measurements (mean error +/- SD = 8.2 +/- 3.4, n = 6) can
      be obtained using conventional velocity imaging techniques. Optimization of the
      method will require the application of rapid imaging techniques and the
      development of strategies for obtaining a more localized measurement. With these
      improvements, our results suggest that MR-based measurement of pulse pressure and
      related elastic parameters is feasible.

PMID- 9256101
TI  - Quantitative studies of magnetization transfer by selective excitation and T1
      recovery.
AB  - Water proton longitudinal relaxation has been measured in agar and cross-linked
      bovine serum albumin (BSA) using modified selective excitation (Goldman-Shen and
      Edzes-Samulski) pulse sequences. The resulting recovery curves are fit to
      biexponentials. The fast recovery rate gives magnetization transfer (MT)
      information, which is complementary to that given by steady-state saturation
      methods. This rate provides an estimate of the strength of the coupling of the
      immobile proton pool to the mobile proton pool. Near their optimal pulse power
      values, the Goldman-Shen and Edzes-Samulski sequences give fast recovery rates
      that agree with each other. However, these measured fast recovery rates are
      dependent on the pulse power, an effect not predicted by the coupled two-pool
      model. For 8% agar and 17% BSA, both methods (at optimal pulse powers) give rates
      in the neighborhoods of 210 and 64 Hz, respectively. The Goldman-Shen and Edzes
      Samulski pulse sequences have several advantages over those techniques based on
      steady state saturation: no long saturating pulses, shorter measurement time, and
      reduced necessity for making lineshape or fitting technique assumptions. The
      principle disadvantages are smaller effects on the NMR signal, less complete
      characterization of the MT system, and, in the case of the Goldman-Shen sequence,
      greater pulse power.

PMID- 9256102
TI  - Evidence for the exchange of arterial spin-labeled water with tissue water in rat
      brain from diffusion-sensitized measurements of perfusion.
AB  - The extraction fraction of vascular water in rat brain is investigated by means
      of diffusion measurements of arterial spin labeled water at varying cerebral
      blood flow (CBF) values. The apparent diffusion coefficient (ADC) of the
      difference of the proton magnetization signal in the brain acquired with and
      without continuous arterial spin labeling is modeled to provide a measure of the
      amount of arterial water in tissue and vasculature and thus of the extraction
      fraction. The tissue and vascular portion of the arterial spin labeled water are
      differentiated based on their diffusion characteristics in a manner analogous to
      the intravoxel incoherent motion (IVIM) method. The amount of labeled arterial
      water that exchanges with tissue water is determined by estimating the fraction
      of the total signal that is associated with the slow-decaying component of a
      biexponential fit to the normalized difference signal between the magnetization
      of brain tissue acquired with and without arterial spin labeling. The results
      indicate that, at normal CBF (1.15 +/- 0.21 ml x g(-1) x min[-1]), about 90% of
      the arterial spin labeled water diffuses with an ADC of (1.21 +/- 0.37) x 10[-3]
      mm2 s[-1]), which is equal to tissue. At high CBF, an increasing fraction of the
      labeling water has a fast-pseudo-diffusion coefficient due to a decrease in water
      extraction fractions. The results also show that the contribution of vascular
      water to the measurement of perfusion by techniques that use endogenous water as
      a tracer can be efficiently eliminated by the use of diffusion sensitizing
      gradients with small effective b values (b approximately 20 s/mm2), enabling
      these techniques to monitor true changes in tissue perfusion.

PMID- 9256103
TI  - Determination of laser-induced temperature distributions using echo-shifted
      TurboFLASH.
AB  - An echo-shifted TurboFLASH sequence implemented on a clinical whole body MR
      scanner was used to determine thermal changes in tissue. With this snapshot-like
      data acquisition, temperature-related phase shifts were measured with a temporal
      resolution of 1.3 s. For different types of tissue (postmortem porcine brain,
      liver, and muscle) the temperature coefficients of the proton chemical shift were
      recorded during uniform heating of the specimen in a water bath. The specific
      temperature-dependent frequency shifts appeared similar to the proton chemical
      shift of free water (-0.01 ppm/degrees C). With this method, laser-induced
      ablation in postmortem porcine brain was monitored by temperature mapping.
      Comparison of the induced temperature profiles measured with NiCrNi-thermocouples
      with the MR calculated profiles demonstrated excellent temperature sensitivity
      and accuracy for this method of MR thermometry, with a maximum deviation of the
      determined temperatures of only 1.8 degrees C. This investigation was designed as
      a feasibility study for this rapid version of the phase mapping method, and no in
      vivo studies were performed.

PMID- 9256104
TI  - MRI using piecewise-linear spiral trajectory.
AB  - A new generation of high power gradient systems which allow much faster MR
      imaging as well as shorter echo times has recently become available. Some of
      these high-speed gradient systems impose limits on the percentage of time during
      which the gradient can change in amplitude (slewing duty cycle). While this
      limitation may be immaterial to many 2DFT and echo planar imaging methods, a
      traditional circular spiral trajectory is difficult to use on these systems
      because its gradient waveforms change during the entire course of the trajectory
      so that the slewing duty cycle during the readout period is 100%. We describe a
      piecewise-linear spiral trajectory which is composed of linear segments and
      rounded corners. This trajectory reduces the slewing duty cycle while maintaining
      the desirable imaging properties of circular spirals including interleaving by
      simple gradient rotation. For one representative example, the slewing duty cycle
      is reduced to 46%. A conventional gridding method was used for image
      reconstruction, but a new numerical algorithm to calculate the density
      compensation factor was required. Use of piecewise-linear spiral trajectories
      reduces the impact imposed by limited gradient slewing duty cycle.

PMID- 9256105
TI  - Catheter visualization using locally induced, actively controlled field
      inhomogeneities.
AB  - A new technique for visualization of interventional devices using MR is
      presented. A prototype catheter was equipped with a thin copper wire loop,
      leading from the proximal end to the tip and back. A small current (10-150 mA)
      through these two parts of a wire induces a local magnetic field along the
      catheter. Introduction of this catheter into the main magnetic field of the MR
      imager locally disturbs the homogeneity of the magnetic field. Image locations
      within the locally induced fields appear dark due to signal loss, and the extent
      of this effect can be varied during the procedure by simply adjusting the
      current. Different dedicated wire configurations allow visualization of the
      catheter in its whole length or in parts, i.e., with markers for balloons. Fast
      gradient echo sequences that provide a bright signal from inflowing blood are
      used for rapid imaging.

PMID- 9256106
TI  - In vivo imaging of extraction fraction of low molecular weight MR contrast agents
      and perfusion rate in rodent tumors.
AB  - Tissue uptake of a fully extractable MR detectable tracer, deuterated water
      (D2O), was compared with that of a less extractable contrast agent, Gadolinium
      DTPA-dimeglumine (Gd-DTPA), in rodent tumor and muscle tissue. This dual tracer
      method allowed calculation of relative (to muscle) tissue perfusion and
      extraction fraction of Gd-DTPA in each image pixel in vivo. Solutions of Gd-DTPA
      and D2O were injected intravenously into Fisher female rats (n = 9) with R3230
      mammary adenocarcinomas implanted in the hind limb. Perfusion rate was
      approximately two times greater (P < 0.005 by paired t test) in tumor than in
      muscle. Gd-DTPA extraction fraction at the interface between tumor and muscle was
      2.0 times the extraction fraction in normal muscle (P < 0.005 by paired t test).
      Extraction fraction at the tumor center was 1.6 times the extraction fraction in
      muscle (P < 0.01 by paired t test). High extraction fraction of Gd-DTPA
      correlated with high capillary permeability determined from Evans Blue staining.
      Low molecular weight Gd-DTPA derivatives are widely used in clinical practice,
      and their extraction fractions are crucial determinants of image contrast during
      the first few passes of the contrast agent bolus. Therefore spatially resolved
      measurements of contrast agent extraction fractions obtained in vivo have
      significant clinical utility. The data demonstrate that extraction of low
      molecular weight tracers is sensitive to increased permeability in tumor
      vasculature and that this increased permeability can be imaged.

PMID- 9256107
TI  - Highly selective water and fat imaging applying multislice sequences without
      sensitivity to B1 field inhomogeneities.
AB  - Improved selectivity to one chemical shift component was obtained using
      simultaneous slice-selective and chemical shift-selective excitation in sequences
      with usual spin-echo refocusing. The new type of sequences can be applied on
      modern whole-body units and permits multislice operation. Spatial-spectral
      excitation is based on prior research in this field, but the proposed improved
      version provides off-center slice excitation by the usual processing of the RF
      pulse envelopes. In addition, no irregular gradient shapes are necessary. The
      required B0 homogeneity of the new method is similar to conventional "fat-sat"
      techniques. In contrast to fat-sat methods, selectivity to water is not reduced
      by unavoidable misadjustments of the transmitter or B1 field inhomogeneities in
      the newly developed approach. Thus, the reported method has the potential to
      replace standard frequency selective fat-sat sequences for most applications.

PMID- 9256108
TI  - The distribution of lithium in rat brain and muscle in vivo by 7Li NMR imaging.
AB  - The regional distribution of lithium (Li) in vivo was determined on a relative
      basis in the brain and muscle of rats by 7Li NMR imaging. Both high resolution
      7Li NMR spectroscopy and atomic absorption spectrophotometry were performed on
      extracts of brain and muscle tissue from the same rats. The average in vivo
      results were generally in good agreement with the corresponding average in vitro
      results, despite the relatively low signal-to-noise ratio of the in vivo images.
      There was good agreement between the two in vitro methods of analysis, both on
      average and for individual animals. Significant differences were found in vivo
      among Li concentration ratios for the various brain regions and muscle by 7Li
      imaging, as well as by the in vitro methods.

PMID- 9256109
TI  - Triple quantum sodium imaging of articular cartilage.
AB  - Triple quantum (TQ) sodium imaging of bovine articular cartilage is presented.
      True triple quantum imaging sequence was modified to incorporate asymmetric echo
      acquisition. Triple quantum signal expression in the presence of residual
      quadrupolar interaction is presented. The filtering capability of the sequence is
      first demonstrated on an agarose phantom. Both single and triple quantum images
      of articular cartilage are compared. The TQ image shows non-zero signal intensity
      solely from cartilage, indicating complete suppression of signals from bone
      marrow and saline. The advantages of TQ imaging of articular cartilage, its
      feasibility in in vivo situations and further improvements in SNR are described.

PMID- 9256110
TI  - Hormonally induced modulation in the phosphate metabolites of breast cancer:
      analysis of in vivo 31P MRS signals with a modified prony method.
AB  - A modified Prony method (MPM) was applied to analyze the main signals present in
      spatially resolved 31P NMR spectra of MCF7 breast tumors implanted in nude mice.
      First, the method was tested on synthetic data to establish its limits of
      reliability. Its performance with respect to peak identification and
      quantification of signal intensities was then exploited on data from three
      implanted tumors during hormonal manipulation with estrogen and the
      antiestrogenic drug tamoxifen. The phosphomonoester peak was resolved into
      phosphocholine (PC) and phosphoethanolamine (PE). Treatment with tamoxifen led to
      a significant reduction in the PE to PE+PC peak amplitude ratio in the tumors
      under consideration. MPM analysis also revealed the presence of two different
      inorganic phosphate pools: a larger acidic pool and a smaller alkaline pool
      during estrogen-induced growth and the reverse during tumor regression.

PMID- 9256111
TI  - Experimental determination of the BOLD field strength dependence in vessels and
      tissue.
AB  - High resolution functional MRI (fMRI) experiments were performed in human visual
      cortex at 0.5, 1.5, and 4 T to determine the blood oxygenation level dependent
      (BOLD) field strength response within regions of obvious venous vessels and
      cortical gray matter ("tissue"). T2*-weighted FLASH images were collected in
      single- and multi-echo mode and used to determine the intrinsic BOLD parameters,
      namely, signal-to-noise ratio (psi), the apparent transverse relaxation rate
      (R2*) and the change in R2* (deltaR2*) between the activated and baseline states.
      The authors find the average percentage signal change (deltaS/S, measured at TE =
      T2*) to be large in vessels (13.3 +/- 2.3%, 18.4 +/- 4.0%, and 15.1 +/- 1.2%)
      compared with that in tissue (1.4 +/- 0.7%, 1.9 +/- 0.7%, and 3.3 +/- 0.2%) at
      0.5, 1.5, and 4 T, respectively. The signal-to-noise ratio in optimized, fully
      relaxed proton density weighted gradient echo images was found to increase
      linearly with respect to the static magnetic field strength (B0). The predicted
      upper bound on BOLD contrast-to-noise ratio (deltaS/R)max as a function of field
      strength was calculated and found to behave less than linearly in voxels
      containing vessels larger than the voxel itself and greater than linearly in
      voxels containing a mixture of capillaries and veins/venules with a diameter less
      than that of the voxel.

PMID- 9256112
TI  - Quantitative regional brain water measurement with magnetic resonance imaging in
      a focal ischemia model.
AB  - Therapeutic approaches to cerebral edema require an understanding of both the
      magnitude and location of changes in brain water content. It is desirable to have
      a sensitive, accurate means of measuring brain water noninvasively so that
      effective therapies for cerebral edema in stroke, head trauma, and other
      conditions can be investigated. In this work, a three-dimensional magnetic
      resonance imaging technique that is able to provide both spin density and T1
      simultaneously is described. This method was used to quantitate regional changes
      in brain water content in a rat model of focal cerebral ischemia. Brain water
      contents estimated from both relative spin density and relative T1 measurements
      made in vivo were compared with ex vivo measurements of relative tissue water
      content based on the wet-dry technique. Correlation coefficients of 0.95 and 0.98
      were obtained between the wet-dry measurements and magnetic resonance
      measurements of T1 and spin density, respectively. Notably, the slope of the
      relationship between T1 and tissue water content changed dramatically after the
      injection of a paramagnetic contrast agent while precontrast and postcontrast
      spin density measurements remained essentially invariant. In addition, a plot of
      absolute spin density (obtained by normalizing spin density from agar gelatin
      phantoms of different water contents to the spin density of a sample of 100%
      water) was linearly related to wet-dry measurements with a slope of 0.99 (R2 =
      0.99).

PMID- 9256113
TI  - Improved water and lipid suppression for 3D PRESS CSI using RF band selective
      inversion with gradient dephasing (BASING).
AB  - A T1 insensitive solvent suppression technique-band selective inversion with
      gradient dephasing (BASING)-was developed to suppress water and lipids for 1H
      magnetic resonance spectroscopy (MRS). BASING, which consists of a frequency
      selective RF inversion pulse surrounded by spoiler gradient pulses of opposite
      signs, was used to dephase stopband resonances and minimally impact passband
      metabolites. Passband phase linearity was achieved with a dual BASING scheme.
      Using the Shinnar-Le Roux algorithm, a highpass filter was designed to suppress
      water and rephase the lactate methyl doublet independently of TE, and water/lipid
      bandstop filters were designed for the brain and prostate. Phantom and in vivo
      experimental 3D PRESS CSI data were acquired at 1.5 T to compare BASING with
      CHESS and STIR suppression. With BASING, the measured suppression factor was over
      100 times higher than with CHESS or STIR causing baseline distortions to be
      removed. It was shown that BASING can be incorporated into a variety of sequences
      to offer improved suppression in the presence of B1 and T1 inhomogeneites.

PMID- 9256114
TI  - Motion-adapted gating based on k-space weighting for reduction of respiratory
      motion artifacts.
AB  - A new modified type of gating is presented that shows the ability to reduce the
      total scan time with almost conserved image quality compared with conventional
      gating. This new motion-adapted gating approach is based on a k-space-dependent
      gating threshold function. MR data acquired are only accepted if the motion
      induced displacements measured from a reference position are below the chosen
      gating threshold function. During the MR measurement the scanner analyses
      respiratory motion decides in real-time which data in k-space could be measured
      according to the gating threshold function and performs data acquisition. In the
      present paper the approach will be described and discussed. Simulations based on
      in vivo data and initial in vivo experiments are presented to compare different
      variants of the new approach mutually and to the conventional technique. The
      analysis given is focused on spin warp type sequences, which are the best
      candidates for this approach.

PMID- 9256115
TI  - Direct observation of resolved intracellular and extracellular water signals in
      intact human red blood cells using 1H MAS NMR spectroscopy.
AB  - High resolution 400 MHz 1H NMR spectra of red blood cell suspensions when
      measured using magic angle spinning (MAS) show two water resonances separated by
      15 Hz. Based on addition of a paramagnetic Mn-EDTA complex, measurement of
      relaxation times and variation of extracellular H2O/D2O ratios, these have been
      assigned as intracellular (linewidth 17.5 Hz) and extracellular water (linewidth
      4.6 Hz). This is the first direct observation of intracellular water using NMR
      spectroscopy and the 1H MAS NMR spectroscopic approach offers the possibility of
      studying directly the compartmentation of substances in cells and kinetics of
      molecular transport.

PMID- 9256116
TI  - A dual approach to linogram imaging for MRI.
AB  - An alternate scheme for linogram image reconstruction, which is more logical from
      the viewpoint of its applicability to MRI data, is presented here. As a result,
      an intermediate step for this method, the direct Fourier method (DFM) gives the
      same results as the earlier developed general reconstruction algorithm labeled as
      the linogram method (LM). However, the two differ in the pathways taken to the
      solution. As a result, an intermediate step for DFM corresponds directly with the
      geometry of linogram data collected for MRI, in contrast to the LM
      reconstruction. The two reconstruction methods are delineated within the context
      of MRI data reconstruction, and applied to reconstruct images from linogram spin
      echo data of a physical phantom, obtained on a clinical 1.5 T scanner.

PMID- 9256117
TI  - Chemotherapy dose escalation: case unproven.

PMID- 9256118
TI  - Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal
      radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's
      disease in pediatric patients: a Pediatric Oncology Group study.
AB  - PURPOSE: To determine whether the addition of low-dose total-nodal irradiation
      (TNI) in pediatric patients with advanced-stage Hodgkin's disease who have
      received eight cycles of alternating mechlorethamine, vincristine, procarbazine,
      and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine
      (ABVD) will improve the event-free survival (EFS) and overall survival (OS) when
      compared with patients who have received chemotherapy only. PATIENTS AND METHODS:
      At diagnosis, 183 children and adolescents with stages IIB, IIIA2, IIIB, and IV
      Hodgkin's disease were randomized to receive eight cycles of alternating MOPP
      ABVD with or without low-dose TNI. RESULTS: Of 183 patients, four were rendered
      ineligible before treatment was initiated. One hundred sixty-one of 179 patients
      (90%) were in complete remission (CR) at the completion of eight cycles of
      alternating MOPP-ABVD; 81 were in the chemotherapy-only group and proceeded to
      observation off therapy, whereas 80 of 161 were to receive combined modality
      therapy (CMT). Nine of 80 patients randomized at the time of diagnosis to receive
      CMT did not receive radiation (RT) because of a protocol violation, but were
      monitored for EFS and OS and included in all analyses. The estimated EFS and OS
      rates at 5 years for the 179 eligible patients are 79% and 92%, respectively. The
      actuarial EFS at 5 years was 80% for patients who received CMT and 79% for
      patients who received MOPP-ABVD only. The OS for the former group is estimated to
      be 87% and for the latter patients 96%. Age < or = 13 years of age at diagnosis
      and the attainment of a clinical CR after three cycles of chemotherapy were
      associated with a statistically significant improved EFS. CONCLUSION: Our results
      indicate that after the delivery of eight cycles of MOPP-ABVD, the addition of
      low-dose RT does not improve the estimated EFS or OS in pediatric patients with
      advanced-stage Hodgkin's disease.

PMID- 9256119
TI  - Phase I/II study of idarubicin given with continuous infusion fludarabine
      followed by continuous infusion cytarabine in children with acute leukemia: a
      report from the Children's Cancer Group.
AB  - PURPOSE: The Children's Cancer Group (CCG) undertook a phase I study (CCG-0922)
      to determine a tolerable dose of idarubicin given with fludarabine and cytarabine
      in children with relapsed or refractory leukemia. The phase I study was extended
      to a limited phase II study to assess the activity of this combination in
      children with acute myelogenous leukemia (AML). PATIENTS AND METHODS: This was a
      multiinstitutional study within the CCG. Eleven patients were entered onto the
      phase I study: seven with AML, three with acute lymphoblastic leukemia (ALL), and
      one with chronic myelogenous leukemia (CML). The maximal-tolerated dose (MTD) of
      fludarabine and cytarabine determined in a previous study was a fludarabine
      loading dose (LD) of 10.5 mg/m2 followed by a continuous infusion (CI) of 30.5
      mg/m2/24 hours for 48 hours, followed by cytarabine LD 390 mg/m2, then CI 101
      mg/m2/h for 72 hours. Idarubicin was given at three dose levels: 6, 9, and 12
      mg/m2 intravenously (I.V.) on days 0, 1, and 2. The phase II portion of the trial
      included 10 additional patients with relapsed or refractory AML. RESULTS: A dose
      of idarubicin 12 mg/m2/d for 3 days given in combination with fludarabine and
      cytarabine was tolerated. The major toxicity encountered was hematologic.
      Nonhematologic toxicities included transaminase elevations, hyperbilirubinemia,
      and infections. Eight of 10 patients with AML in the phase II portion (12 mg/m2
      idarubicin) achieved a complete remission (CR). CONCLUSION: This combination is
      active in patients with relapsed or refractory AML. The major toxicity
      encountered is hematologic. This regimen may be useful therapy for AML and should
      be compared with standard induction therapy in children with newly diagnosed AML.

PMID- 9256120
TI  - Role of cranial radiotherapy for childhood T-cell acute lymphoblastic leukemia
      with high WBC count and good response to prednisone. Associazione Italiana
      Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster groups.
AB  - PURPOSE: The ALL-BFM 90 and AIEOP-ALL 91 studies share the same treatment
      backbone and have 5-year event-free survival (EFS) rates close to 75%. This study
      evaluated the impact of differing presymptomatic CNS therapies in T-cell acute
      lymphoblastic leukemia (T-ALL) patients with a good response to prednisone (PGR)
      according to WBC count and Berlin-Frankfurt-Munster (BFM) risk factor (RF).
      PATIENTS: A total of 192 patients (141 boys; median age, 7.5 years) with T-ALL,
      PGR, RF less than 1.7, and no CNS leukemia diagnosed between 1990 and 1995 were
      enrolled onto the ALL-BFM 90 (n = 123) or AIEOP-ALL 91 (n = 69) study.
      Presymptomatic CNS therapy consisted of cranial radiation (CRT) and intrathecal
      methotrexate (I.T. MTX) (11 doses) in the BFM study and of extended triple
      intrathecal therapy (T.I.T.) (17 doses) in the Associazione Italiana Ematologia
      Oncologia Pediatrica (AIEOP) study. Patients were divided into a low-WBC group
      (WBC count < 100,000/microL) and a high-WBC group (WBC count > 100,000/microL).
      EFS was compared using the log-rank test. RESULTS: For patients treated with CRT
      and I.T. MTX (BFM group), the 3-year EFS rate was 89.8% (SE = 3.5) for 99
      patients in the low-WBC group versus 81.9% (SE = 8.2) in the high-WBC group
      (difference not significant). Conversely, for patients treated with T.I.T. alone
      (AIEOP group), the EFS rate was 80.6% (SE = 5.6) in 55 patients with a low WBC
      count versus 17.9% (SE = 11.0) in 14 patients with a high WBC count (P < .001).
      CONCLUSION: These data suggest that CRT may not be necessary in PGR T-ALL
      patients with a WBC count less than 100,000/microL; on the contrary, in patients
      with a high count, extended T.I.T. may be inferior to CRT and I.T. MTX.

PMID- 9256121
TI  - Low-grade astrocytoma: a decade of experience at St. Jude Children's Research
      Hospital.
AB  - PURPOSE: To evaluate the impact of primary tumor site, age at diagnosis, extent
      of resection, and histology on progression-free survival (PFS) in pediatric low
      grade astrocytoma. PATIENTS AND METHODS: Medical, pathologic, and imaging
      information were reviewed for 142 children (ages 2 months to 19 years) with low
      grade astrocytoma treated between January 1984 and July 1994. Gross total
      resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with
      biopsy or less aggressive resection used predominantly for tumors in other sites.
      Surgery was followed by observation in 107 cases, radiation therapy in 31, and
      chemotherapy in four. RESULTS: The overall survival rate was 90% +/- 3% (SE) at 4
      years. PFS was significantly better for patients with cerebellar and cerebral
      hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006).
      Within the former group, there was no significant difference in PFS for patients
      in whom GTR was achieved versus those with incomplete resections (4-year
      estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v
      astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis
      that controlled for tumor site and patient age. Patients younger than 5 years at
      diagnosis had a significantly poorer PFS than older children, regardless of
      histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent
      disease was effective in a majority of patients, but appeared more successful in
      patients with hemispheric than thalamic or hypothalamic tumors. CONCLUSION: The
      overall survival in this series of pediatric low-grade astrocytomas is excellent.
      Age at diagnosis and tumor location, but not histology, had a significant impact
      on PFS. Efforts to improve treatment outcome should focus on young patients (< 5
      years) and on those with central midline tumors. The majority of patients with
      completely resected hemispheric tumors were monitored without further therapy,
      which supports attempted GTR of cerebral and cerebellar hemisphere low-grade
      astrocytoma.

PMID- 9256122
TI  - Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF
      of children who receive methotrexate for the treatment of cancer.
AB  - PURPOSE: Folate deficiency, either by diet or drug, increases plasma homocysteine
      (Hcy). Hcy damages cerebrovascular endothelium, and hyperhomocysteinemia is a
      risk factor for stroke. Hcy is metabolized to excitatory amino acid (EAA)
      neurotransmitters, such as homocysteic acid (HCA) and cysteine sulfinic acid
      (CSA), which may cause seizures and excitotoxic neuronal death. We postulated
      that excess Hcy and EAA neurotransmitters may partly mediate methotrexate (MTX)
      associated neurotoxicity. PATIENTS AND METHODS: In this retrospective analysis,
      we used high-performance liquid chromatography (HPLC) to measure Hcy, HCA, and
      CSA in CSF from two groups of children: (1) a control group of patients with no
      MTX exposure, and (2) a treatment group of patients who had received MTX no more
      than 7 days before a scheduled lumbar puncture. RESULTS: The treatment group had
      a significantly (P = .0255) greater concentration of Hcy in CSF (0.814 micromol/L
      +/- 0.215 [mean +/- SEM], n = 23) than the control group (0.210 micromol/L +/-
      0.028, n = 34). HCA and CSA were not detected in CSF from control patients (n =
      29); however, MTX caused marked accumulation of CSF HCA (119.1 micromol/L +/-
      32.0, n = 16) and CSA (28.4 micromol/L +/- 7.7, n = 16) in the treatment group.
      Patients with neurologic toxicity at the time of lumbar puncture had many of the
      highest concentrations of Hcy, HCA, and CSA. CONCLUSION: These data support our
      hypothesis that MTX-associated neurotoxicity may be mediated by Hcy and
      excitotoxic neurotransmitters.

PMID- 9256123
TI  - Detection of metastatic neuroblastoma in bone marrow: when is routine marrow
      histology insensitive?
AB  - PURPOSE: To measure the sensitivity of histologic examination in detecting
      metastatic solid tumor in bone marrow. PATIENTS AND METHODS: A total of 145
      patients with stage 4 neuroblastoma underwent 840 marrow examinations, each
      consisting of six sites (four aspirates and two biopsies), from October 1990 to
      June 1996 at Memorial Sloan-Kettering Cancer Center. Metastasis was detected by
      either histology (aspirate by Wright-Giemse and biopsy by Hematoxylin-Eosin
      stains) or immunostaining of aspirates using anti-G(D2) monoclonal antibodies.
      RESULTS: The absence of tumor by histology at a single marrow site was a poor
      guarantee of the absence of disease. The number of false-negative sites increased
      as the percent of G(D2)-positive tumor cells in the marrow decreased: zero of six
      if tumor cell count was > or = 1%, and approximately six of six sites if < or =
      0.003%. Sensitivity was comparable between marrow aspirate and biopsy. A lower
      bound (LB) for the probability of false-negative histology was calculated from
      the (1) discordance among the six marrow samplings and (2) comparison with
      immunofluorescence. When disease was extensive (eg, at diagnosis), the LB was
      0.13 and 0.3, respectively. After treatment, it increased to 0.37 and 0.8.
      Examining multiple marrow sites can decrease the LB to 0.15. However, at least
      three sites have to be negative at relapse, six at diagnosis, and more than 50
      during treatment or off-therapy follow-up. The marginal decrease in the LB by
      additional samplings rapidly diminished to less than 0.05 after two sites.
      CONCLUSION: Except at diagnosis and relapse when gross disease is present, marrow
      sampling by histology has limited sensitivity. Current practice grossly
      underestimates the true prevalence of marrow disease.

PMID- 9256124
TI  - Detection of circulating melanoma cells by specific amplification of tyrosinase
      complementary DNA is not a reliable tumor marker in melanoma patients: a clinical
      two-center study.
AB  - PURPOSE: Recently, the reverse-transcription polymerase chain reaction (RT-PCR)
      of tyrosinase messenger RNA (mRNA) was reported to be a useful tool for the
      detection of circulating tumor cells in the peripheral blood of melanoma
      patients. Our aim was to evaluate critically the diagnostic value of this marker
      by investigating a significant number of patients in different stages of the
      disease in a two-center study. PATIENTS AND METHODS: Different techniques of
      blood collection, RNA isolation, and RT-PCR were compared, and the detectability
      of tyrosinase mRNA was tested using nine different melanoma cell lines. The
      sensitivity of the method was confirmed by blood spiking experiments and the
      specificity by restriction enzyme analysis. Subsequently, a total of 153 blood
      samples from 137 individuals (30 healthy subjects, five basal cell carcinoma, and
      102 melanoma patients) were investigated. RESULTS: The detection level of
      melanoma cells differed between the cell lines tested. However, we could
      reproducibly detect single melanoma cells by spiking whole blood samples from
      healthy volunteers. One of 43 patients with primary melanoma (2.3%), zero of 15
      patients with regional metastasis (0%), and 12 of 44 patients with advanced
      disease (27.3%) were found to be RT-PCR positive. All blood samples obtained from
      controls and patients with basal cell carcinoma were tyrosinose mRNA negative.
      CONCLUSION: Our data support the recent doubts that the detection of circulating
      tumor cells in melanoma patients using the tyrosinase mRNA RT-PCR is not
      sensitive enough to be used either as a melanoma progression marker in early
      stages of the disease or to monitor therapy in advanced stages of the disease.

PMID- 9256125
TI  - Evaluation of tyrosinase mRNA as a tumor marker in the blood of melanoma
      patients.
AB  - PURPOSE: The value of tyrosinase messenger RNA (mRNA) detection in the peripheral
      blood by reverse-transcription polymerase chain reaction (RT-PCR) as a melanoma
      marker remains controversial. The purpose of this study was to compare the
      sensitivities of two different blood processing techniques for tyrosinase mRNA
      detection and evaluate its potential clinical value. METHODS: A total of 50
      patients with progressive stage IV melanoma was studied. Two blood processing
      methods were used: RNA extraction from the whole blood and RNA extraction from
      density gradient-isolated peripheral-blood mononuclear cells (PBMC). The RNA
      samples were tested with a sensitive nested-primer RT-PCR assay. RT-PCR results
      were also correlated with serum lactate dehydrogenase (LDH), treatment status,
      and presence of visceral versus nonvisceral metastases. RESULTS: Thirteen (26%)
      of the density gradient and five (10%) of the whole blood processed samples were
      PCR positive (P = .011). Serum LDH levels were found to be significantly higher
      in PCR-positive PBMC-processed patients (P = .015). There was no significant
      difference in the detection rates between visceral versus nonvisceral metastases
      or between prior treatment versus no prior treatment. CONCLUSION: Using a density
      gradient method to process the blood samples resulted in a higher detection rate
      of tyrosinase mRNA than extracting the RNA from the whole blood. However, the
      relatively low sensitivity in patients with disseminated and progressive disease
      compared with other reports suggests that tyrosinase mRNA may be of limited value
      in the management of malignant melanoma.

PMID- 9256126
TI  - Prognostic factors associated with long-term survival for retroperitoneal
      sarcoma: implications for management.
AB  - PURPOSE: Retroperitoneal soft tissue sarcomas are rare tumors. Studies
      characterizing long-term follow-up and patterns of recurrence are limited. The
      purpose of this analysis is to identify patterns of recurrence and prognostic
      factors associated with long-term survival after resection of retroperitoneal
      soft tissue sarcomas. METHODS: Between July 1, 1982, and June 30, 1990, 198 adult
      patients were identified from our prospective soft tissue sarcoma database
      carrying the diagnosis of retroperitoneal soft tissue sarcoma who were eligible
      for > or = 5 years of follow-up. Of these, 48 patients (25%) were documented to
      be alive > or = 5 years from the time of operation. Statistical analysis was by
      log-rank or Wilcoxon test for univariate analysis. Multivariate analysis was by
      the Cox model. RESULTS: The recurrence rate during the follow-up period was
      approximately 5% per year from the time of initial operation. Of the patients who
      were disease-free for > or = 5 years from initial surgery, 40% recurred by 10
      years. Radiation therapy was the only factor significant (P = .02) for a
      reduction in the risk of local recurrence. Age < or = 50 years and high-grade
      tumors were significant factors (P = .003 and .009, respectively) for an
      increased risk of distant metastasis. Incomplete gross resection was the only
      factor significant for an increased risk of tumor mortality (P = .003).
      CONCLUSION: Complete surgical resection at the time of primary presentation is
      likely to afford the best chance for long-term survival. With long-term follow
      up, it is clear that recurrence will continue to occur, and a 5-year disease-free
      interval is not a cure. Patients with an incomplete initial resection, age less
      than 50 years, and high-grade tumors are candidates for investigational adjuvant
      therapy.

PMID- 9256127
TI  - Randomized trial of alternating versus sequential radiotherapy/chemotherapy in
      limited-disease patients with small-cell lung cancer: a European Organization for
      Research and Treatment of Cancer Lung Cancer Cooperative Group Study.
AB  - PURPOSE: To evaluate the effectiveness of alternating or sequential schedules of
      cyclophosphamide, doxorubicin, and etoposide (CDE) chemotherapy and irradiation
      in patients with previously untreated small-cell lung cancer (SCLC). MATERIALS
      AND METHODS: A total of 335 eligible patients were randomized between five
      courses of CDE chemotherapy followed by thoracic irradiation 50 Gy in 20 daily
      fractions (S) and the same total dose of chemotherapy and irradiation split into
      four courses of five daily fractions delivered on days 14 to 21 of the second and
      subsequent chemotherapy courses (A). Patients had a median age of 61 years
      (range, 33 to 75); 224 (66%) were male; the Eastern Cooperative Oncology Group
      (ECOG) performance status (PS) was 0 or 1 in 311; and 254 had weight loss less
      than 10%. RESULTS: The overall median survival duration was 15 months, with 62%
      (95% confidence interval [CI], 57% to 67%) 1-year, 25% (95% CI, 20% to 30%) 2
      year, and 14% (95% CI, 10% to 18%) 3-year survival rates. There was no
      significant difference between the arms. The median survival time was 14 months
      in A and 15 months in S. One-year survival was 60% in A (95% CI, 53% to 67%) and
      64% in S (95% CI, 57% to 71%); 2-year survival was 26% in A (95% CI, 19% to 33%)
      and 23% in S (95% CI, 16% to 30%); and 3-year survival was 12% in A (95% CI, 6%
      to 18%) and 15% in S (95% CI, 9% to 21%). World Health Organization (WHO) grade 3
      and 4 neutropenia occurred in 90% of A and 77% of S patients (P < .001) and WHO
      grade 3 and 4 thrombocytopenia in 33% of A and 20% of S patients (P < .001).
      Rates of other acute and late toxicities were similar in both arms. Hematologic
      toxicity compromised treatment dose delivery; less than 50% of A patients
      received greater than 95% of prescribed chemotherapy and 77% their full radiation
      course, compared with 60% and 93% for arm S (P < .009). Local relapse was the
      site of first failure in 60% of all patients and 75% of these suffered an in
      field relapse; no difference could be seen between the two arms. CONCLUSION: This
      trial failed to confirm the superiority of an alternating schedule of delivery.
      For this combination of chemotherapy and irradiation, hematologic toxicity
      compromised treatment delivery and could have contributed to the overall result.
      The poor rates of local control are disappointing and require intensification of
      the radiation therapy strategy.

PMID- 9256128
TI  - Effect of amifostine on toxicities associated with sequential chemotherapy and
      radiation therapy for unresectable non-small-cell lung cancer: results of a phase
      II trial.
AB  - PURPOSE: To determine the effect of amifostine on the safety and efficacy of
      induction chemotherapy with high-dose cisplatin and vinblastine followed by large
      field thoracic irradiation to 60 Gy in patients with stage IIIA or IIIB non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six patients with
      unresectable stage IIIA or IIIB NSCLC were entered onto the study between May
      1991 and November 1994. Patients received amifostine (740 or 910 mg/m2) followed
      by cisplatin (120 mg/m2) on days 1 and 29. Vinblastine (5 mg/m2) was given weekly
      for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients
      received amifostine (340 mg/m2 4 days a week for 5 weeks, or 200 mg/m2 5 days a
      week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a
      total dose of 60 Gy in 6 weeks. RESULTS: Twenty-five patients were assessable for
      response and survival. The objective response rate was 60%. One-, 2-, and 3-year
      survival rates were 55%, 23%, and 23%. There was no grade 3 or greater renal
      toxicity during chemotherapy or grade 3 or greater esophagitis during radiation
      therapy. Neutropenia (secondary to vinblastine use) was the only grade 4
      toxicity. There were no treatment-related deaths. CONCLUSION: Amifostine can be
      administered safely with high-dose cisplatin, vinblastine, and radiation therapy
      for NSCLC. The response rate and survival data provide no evidence that
      amifostine impairs response to treatment. Amifostine appears to reduce cisplatin
      related nephrotoxicity and radiation-induced esophagitis.

PMID- 9256129
TI  - Immunocytochemical markers in stage I lung cancer: relevance to prognosis.
AB  - PURPOSE: This study investigated the frequency of the expression and prognostic
      significance of a panel of immunocytochemical markers in resected non-small-cell
      lung cancer (NSCLC). PATIENTS AND METHODS: A total of 515 cases of pathologic
      stage I NSCLC were analyzed. The median follow-up time of surviving patients was
      102 months. The following immunocytochemical markers were tested: blood group A
      and precursors of blood antigens; laminin receptor; c-erbB1/epidermal growth
      factor receptor (EGFR) and c-erbB2/Neu; BCl2; p53; and angiogenesis. Kaplan-Meier
      estimates of survival and time to recurrence were calculated for clinical
      variables and biologic markers using the Cox model for multivariate analysis.
      RESULTS: The pathologic tumor extension (pT) represented the most powerful
      prognostic factor for survival (P = .0008) and time to recurrence (P = .0007).
      None of the immunocytochemical markers emerged as an independent predictive
      factor for survival. Bcl2-positive tumors showed a better time to recurrence (P =
      .03), but the difference lost statistical significance in the multivariate
      analysis. Of interest, in the group of 137 patients classified as pT1N0, both
      EGFR expression and nonangiogenic type of vascular pattern were associated with a
      poorer survival (P = .02). However, data derived from subset analysis must be
      interpreted cautiously. CONCLUSION: Our findings do not support a relevant
      prognostic role of immunocytochemical markers in NSCLC. The evidence is not
      sufficient to alter clinical practice or even to restrict clinical trials of
      adjuvant treatments to predefined biologic subsets of patients.

PMID- 9256130
TI  - Anti-Hu antibodies in patients with small-cell lung cancer: association with
      complete response to therapy and improved survival.
AB  - PURPOSE: Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and
      small-cell lung cancer (SCLC). High titers of HuAb were initially reported in
      serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy
      (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients
      without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of
      these patients may grow more indolently. Based on these observations, we
      conducted a multicenter prospective study of SCLC patients without PEM/SN to
      determine the incidence and prognostic implications of HuAb. METHODS: Serum
      samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb
      were determined by immunoblot of purified recombinant HuD antigen. RESULTS: HuAb
      were detected in 32 (16%) of the 196 patients. Of the 170 patients who received
      treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with
      limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy
      (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In
      a logistic regression analysis, HuAb status was an independent predictor of
      complete response induction. The probability of achieving a complete response was
      more than five times higher in HuAb-positive than in HuAb-negative patients (odds
      ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate
      analysis indicated that HuAb status was not independently associated with
      survival. CONCLUSION: The presence of HuAb at diagnosis of SCLC is a strong and
      independent predictor of complete response to treatment. This feature accounts
      for the association between HuAb and longer survival.

PMID- 9256131
TI  - Breast conservation and prolonged chemotherapy for locally advanced breast
      cancer: the University of Michigan experience.
AB  - PURPOSE: To determine whether breast conservation and prolonged neoadjuvant
      chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured
      by survival and rate of breast conservation. MATERIALS AND METHODS: Eighty-nine
      patients with stage III disease were enrolled at the University of Michigan (UM)
      onto a prospective nonrandomized trial. Patients received nine 21-day cycles of
      neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and
      cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg
      orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500
      mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to
      14. Patients with a negative biopsy received radiation only, while those with
      residual disease underwent mastectomy and postoperative radiotherapy. Eight more
      cycles of chemohormonal therapy were administered after local-regional therapy.
      RESULTS: The clinical response rate to neoadjuvant therapy was 97%, 28% of
      patients had a complete pathologic response evaluated at biopsy. Five-year
      overall and disease-free survival probabilities were 54% and 44%, respectively.
      The median disease-free survival time was 2.4 years. The 5-year actuarial rates
      of local-regional control with local failure as only first failure were 82% and
      78% following radiotherapy, and mastectomy and radiotherapy, respectively (P =
      .99). CONCLUSION: Prolonged neoadjuvant chemohormonal therapy and biopsy-driven
      local therapy have efficacy in LABC, with 28% of patients being candidates for
      breast conservation and a 5-year overall survival rate of 54%.

PMID- 9256132
TI  - High-dose chemotherapy and stem-cell rescue in the treatment of high-risk breast
      cancer: prognostic indicators of progression-free and overall survival.
AB  - PURPOSE: To examine the predictive value of tumor- and treatment-specific
      prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in
      patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy
      (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and
      September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph
      nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received
      adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and
      either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage,
      tumor size, number of axillary nodes involved, grade and receptor status, and
      types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a
      median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of
      3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval
      [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS
      estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95%
      CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the
      risk of relapse was lower for patients with progesterone receptor (PR)-positive
      tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for
      patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05).
      OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and
      estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05);
      OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21
      13.7; P = .02). In multivariate analysis, PR positivity was associated with
      improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients
      with HRBC is safe and warrants further evaluation. Patients with receptor
      negative, high-grade, or inflammatory tumors require improvement in their
      therapeutic options. Better assessment of the role of HDCT awaits completion of
      ongoing randomized trials.

PMID- 9256133
TI  - HER-2/neu gene amplification characterized by fluorescence in situ hybridization:
      poor prognosis in node-negative breast carcinomas.
AB  - PURPOSE: The HER-2/neu gene codes for a membrane receptor protein that is
      homologous, but distinct from the epidermal growth factor receptor. This
      investigation was performed to validate fluorescence in situ hybridization (FISH)
      as a sensitive and specific method for assessing HER-2/neu gene amplification in
      archival tissue and to test whether this alteration is associated with poor
      prognosis. MATERIALS AND METHODS: HER-2/neu gene amplification was determined by
      FISH in 140 archival breast cancers, previously characterized for gene
      amplification by Southern hybridization or dot-blot hybridization, and for gene
      expression by Northern hybridization, Western immunoblot, or
      immunohistochemistry. A separate cohort of 324 node-negative breast cancers was
      assessed for amplification by FISH to determine the utility of HER-2/neu gene
      amplification. RESULTS: Relative to solid-matrix blotting procedures, FISH
      analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a
      specificity of 100% in 140 breast cancers. Among patients treated by surgery
      only, the relative risks (relative hazard) of early recurrence (recurrent disease
      within 24 months of diagnosis), recurrent disease (at any time), and disease
      related death were statistically significantly associated with amplification. The
      prognostic information contributed by HER-2/neu amplification was independent of
      the other markers studied. CONCLUSION: FISH was an alternative technique for
      determining gene amplification and had some distinct advantages over Southern
      hybridization. Our results demonstrate that HER-2/neu gene amplification in the
      absence of adjuvant therapy is an independent predictor of poor clinical outcome
      and is a stronger discriminant than tumor size. Women with small tumors that had
      gene amplification were at increased risk of recurrence and disease-related
      death.

PMID- 9256134
TI  - Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous
      infusion in metastatic colorectal carcinoma.
AB  - PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical
      activity in metastatic colorectal carcinoma in both chemotherapy-naive and
      fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another
      camptothecin derivative, was selected for clinical development based on
      preclinical activity, including cures in human tumor xenografts resistant to
      standard anticancer agents. We report a phase II trial of 9-AC in patients with
      previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS:
      Colorectal cancer patients with measurable disease, a performance status of 0 to
      2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A
      cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for
      3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles
      (28 days). Patients were assessed for response after two courses. RESULTS:
      Seventeen patients with metastatic colorectal cancer were entered onto this
      trial. No complete or partial responses were noted. Treatment was well tolerated;
      toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis,
      fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in
      four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting
      (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients
      had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute
      granulocyte count (AGC) was 1,500/microL. The median number of courses given was
      two and the median time to disease progression was 8 weeks. CONCLUSION: At the
      dose and schedule used in this trial, 9-AC lacked antitumor activity in
      metastatic colorectal cancer. 9-AC infusion schedules of longer duration are
      currently being investigated in this disease.

PMID- 9256135
TI  - Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.
AB  - PURPOSE: To evaluate the objective tumor response rate and toxicities of patients
      with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT
      11). PATIENTS AND METHODS: A total of 121 patients with advanced colorectal
      carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically
      naive patients--were enrolled between May 1993 and June 1994. Patients were
      treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2
      week rest. RESULTS: Among 90 patients with prior 5-FU chemotherapy, 12 partial
      responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1%
      to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses
      (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as
      measured from time of initial treatment for the two groups was 7.7 months and 7.6
      months, respectively. The major adverse reactions were gastrointestinal and
      hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall
      incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121
      patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or =
      grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with
      prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or
      4 diarrhea demonstrated no association with previous pelvic irradiation.
      CONCLUSION: According to the study design, CPT-11 showed promising activity in
      chemotherapy-naive patients with advanced colorectal carcinoma and modest
      activity in patients with prior 5-FU exposure. The toxicity with this schedule
      appears manageable with appropriate dose modification for individual patient
      tolerance and an intensive loperamide regimen for the management of diarrhea.
      Care should be taken when treating patients with prior pelvic radiotherapy
      because of the increased risk of neutropenia.

PMID- 9256136
TI  - Combined modality therapy for stage II and stage III pancreatic carcinoma.
AB  - PURPOSE: To study the outcome achieved with three-drug chemotherapy and split
      course external-beam radiotherapy as a treatment for unresectable stage II and
      III pancreatic carcinoma. PATIENTS AND METHODS: Radiotherapy was given in three
      cycles of 2 Gy/d on days 1 to 5 and 8 to 12 (total dose, 54 Gy) concurrently with
      fluorouracil (FU) 1,000 mg/m2/d by continuous infusion for 4.5 days, streptozocin
      (STZ) 300 mg/m2 on days 1, 2, and 3 and cisplatin (P) 100 mg/m2 on day 3 of each
      every-28-day cycle. Subsequent treatment consisted of leucovorin (LV) 200 mg/m2
      and FU 600 to 1,000 mg/m2 every 14 days. RESULTS: The median survival time for
      the 35 patients was 15 months and 26% of patients were alive at 24 months.
      Fifteen patients (42.8%) had objective responses to therapy. Six (17%) had a
      complete response (CR). Three of nine patients with partial responses (PRs)
      achieved a radiographic CR within the next 3 months. Nine patients underwent
      attempts at surgical resection: five were resected (median survival time, 31
      months; range, 12.8 to 44.7+), two had no residual disease found at complete
      resection, and three others also had a complete resection. Of four others who
      could not be resected, three underwent intraoperative radiotherapy and one had
      occult metastatic disease. Of primary tumors, 91% did not produce either back
      pain or local gastrointestinal complications for 2 years. The rates of severe
      side effects were stomatitis 15%, anemia 14%, granulocytopenia 6%, and
      thrombocytopenia 6%. CONCLUSION: Palliation and survival compare favorably with
      other series, including many surgical series. The response findings encourage
      studies of both unresectable and (as neoadjuvant therapy) resectable tumors.

PMID- 9256137
TI  - Bicalutamide for advanced prostate cancer: the natural versus treated history of
      disease.
AB  - PURPOSE: To determine the therapeutic effects of bicalutamide 200 mg in patients
      with prostate cancers of different hormone sensitivities. METHODS: Patients with
      progressive prostate cancer were treated with bicalutamide 200 mg daily. Before
      treatment, patients' tumors were classified on the basis of prior hormone
      exposure and by serum testosterone levels into androgen-dependent and androgen
      independent groups. Prior exposure to flutamide and response to flutamide
      withdrawal was also considered. Outcomes were reported independently on the basis
      of posttherapy changes in prostate-specific antigen (PSA), measurable disease,
      and radionuclide bone scans. RESULTS: Outcomes varied by prior hormone exposure
      as a higher proportion of patients with progression of androgen-dependent tumors
      showed posttherapy PSA decreases of more than 50% or more than 80%, measurable
      disease regression, and improvement on radionuclide bone scans than did patients
      with androgen-independent progression. Within the category of androgen
      independent progression, clinical benefit was observed in patients who had
      previously progressed on flutamide, independent of the response to flutamide
      withdrawal. Patients who had progressed on a gonadotropin-releasing hormone
      (GnRH) analog alone had a low response proportion, whereas those who progressed
      after two or more hormone therapies did not respond. Overall, the drug was well
      tolerated. After progression on bicalutamide monotherapy, one third of patients
      with androgen-dependent progression responded to medical castration with a GnRH
      analog. CONCLUSION: Classifying patient tumors on the basis of prior hormone
      exposure permits a more precise estimate of the potential benefit of a specific
      hormone therapy for the individual patient. The precision is further increased by
      reporting the effects of a drug on each parameter of disease independently. The
      difference in outcomes for patients with androgen-independent progression
      suggests that the specific hormone therapy administered and the response to that
      therapy can influence the biology of the relapsing tumor and the sensitivity to
      subsequent therapies. The sensitivity to bicalutamide after progression on
      flutamide deserves further study.

PMID- 9256138
TI  - Effective chemotherapy for advanced CNS embryonal tumors in adults.
AB  - PURPOSE: Embryonal tumors of the CNS include, among others, medulloblastoma,
      cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors
      (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived
      from the pediatric population, since these tumors are uncommon in adulthood. The
      purpose of this study was to examine the rate and duration of response to
      chemotherapy of advanced embryonal CNS tumors in adults. PATIENTS AND METHODS: We
      retrospectively studied all adult (> 18 years of age) patients with advanced
      embryonal tumors of the CNS who received chemotherapy at our institution between
      1976 and 1994. Seventeen consecutive patients were treated with regimens that
      contained either nitrosourea or cisplatin or both sequentially, with no patients
      having received the combination of nitrosourea and cisplatin concurrently.
      RESULTS: In patients who received cisplatin-based chemotherapy, responses were
      observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and
      5% progressed. The median time to progression was 18 months for patients who had
      a CR, 6 months for those with partial response (PR), and 10 months for stable
      patients. Among patients who received nitrosourea-based chemotherapy, PR was
      observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to
      progression was 6 months for patients who had a PR and 6.5 months for stable
      patients. CONCLUSION: In adults with advanced embryonal CNS tumors, conventional
      dose intravenous cisplatin-based chemotherapy regimens are able to produce
      responses in the majority of the patients (84.5%), even as second- or third-line
      regimens. Nitrosourea-based regimens less frequently produce responses (27%).

PMID- 9256139
TI  - Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation,
      response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte
      study on 453 patients older than 69 years.
AB  - PURPOSE: To clarify disease characteristics and optimal treatment for elderly
      patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in
      453 patients older than 69 years with aggressive lymphoma. PATIENTS AND METHODS:
      Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM
      26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients
      received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six
      courses every 3 weeks. RESULTS: The median age was 75 years. Most patients had
      clinically aggressive disease; 30% had one and 53% two or three adverse
      prognostic parameters as defined by the International Prognostic Index. More
      patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but
      the two groups were otherwise well balanced. CTVP treatment was more frequently
      associated with leukopenia, thrombocytopenia, and infectious complications. Death
      during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms,
      respectively (not significant). Forty percent of patients achieved a complete
      response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median
      time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP
      (log-rank test, P < .05). The median survival time was 13 months in both groups;
      however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 =
      4.68, P < .05). Lymphoma progression was the primary cause of death. CONCLUSION:
      Elderly patients with aggressive lymphoma have an aggressive disease with adverse
      prognostic parameters at the time of diagnosis. Slightly longer survival was
      observed for patients treated with an anthracycline-containing regimen.

PMID- 9256140
TI  - Human urinary macrophage colony-stimulating factor reduces the incidence and
      duration of febrile neutropenia and shortens the period required to finish three
      courses of intensive consolidation therapy in acute myeloid leukemia: a double
      blind controlled study.
AB  - PURPOSE: To determine whether macrophage colony-stimulating factor (M-CSF)
      reduces the incidence and duration of febrile neutropenia during three courses of
      intensive consolidation therapy and whether it shortens time to complete
      consolidation therapy. PATIENTS AND METHODS: In 198 adult patients with acute
      myeloid leukemia (AML) in complete remission (CR), M-CSF (8 x 10(6) U/d) or
      placebo was administered from 1 day after the end of each consolidation
      chemotherapy for 14 days. RESULTS: The duration and incidence of febrile
      neutropenia was significantly reduced by 34% (P = .00285) and 17% (P = .02065),
      respectively, in 88 assessable patients in the M-CSF group compared with those in
      94 assessable patients in the placebo group. Patients in the M-CSF group had 565
      days and 133 episodes of febrile neutropenia during 7,901 days at risk, while
      patients in the placebo group had 977 days and 185 episodes during 9,077 days at
      risk. The median period required to finish the three courses of consolidation
      therapy was 93 days in the M-CSF group, which was significantly shorter than 110
      days in placebo group (P = .0050). In the M-CSF group, the recovery of
      neutrophils and platelets was significantly faster (P = .0348 and P = 0.0364,
      respectively), the administration of systemic antimicrobial agents tended to be
      less (P = .0839), and the frequency of platelet transfusion (P = .0259) and the
      total volume of transfused platelets (P = .0292) were significantly less.
      However, there was no significant difference in the disease-free survival.
      CONCLUSION: M-CSF significantly reduced the incidence and duration of febrile
      neutropenia during the intensive consolidation therapy, and shortened the time to
      complete consolidation chemotherapy in AML.

PMID- 9256142
TI  - Phase III placebo-controlled trial of capsaicin cream in the management of
      surgical neuropathic pain in cancer patients.
AB  - PURPOSE: A minority of cancer survivors develops long-term postsurgical
      neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot
      chili peppers, might be useful for treating neuropathic pain, we developed the
      present clinical trial. PATIENTS AND METHODS: Ninety-nine assessable patients
      with postsurgical neuropathic pain were entered onto this study. After
      stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream
      followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A
      capsaicin/placebo cream was to be applied to the painful site four times daily.
      Treatment evaluation was performed by patient-completed weekly questionnaires.
      RESULTS: During the first 8-week study period, the capsaicin-cream arm was
      associated with substantially more skin burning, skin redness, and coughing (P <
      .0001 for each). Nonetheless, treatment was stopped for patient refusal or
      toxicity just as often while patients were receiving the placebo as compared with
      the capsaicin. The capsaicin cream arm had substantially more pain relief (P =
      .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%.
      On completion of the 16-week study period, patients were asked which treatment
      period was most beneficial. Of the responding patients, 60% chose the capsaicin
      arm, 18% chose the placebo arm, and 22% chose neither (P = .001). CONCLUSION: A
      topical capsaicin cream decreases postsurgical neuropathic pain and, despite some
      toxicities, is preferred by patients over a placebo by a three-to-one margin
      among those expressing a preference.

PMID- 9256141
TI  - Phase III double-blind comparison of dolasetron mesylate and ondansetron and an
      evaluation of the additive role of dexamethasone in the prevention of acute and
      delayed nausea and vomiting due to moderately emetogenic chemotherapy.
AB  - PURPOSE: To compare the efficacy of dolasetron and ondansetron in controlling
      nausea and vomiting in the first 24 hours; to evaluate the efficacy when
      dexamethasone is added to either drug in the first 24 hours; and to extend these
      comparisons over 7 days in patients receiving moderately emetogenic chemotherapy.
      PATIENTS AND METHODS: This was a multicenter, double-blind, randomized study with
      six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive
      patients. In arm 1, dolasetron (2.4 mg/kg) was given intravenously (I.V.)
      prechemotherapy, followed 24 hours later by oral dolasetron (200 mg once daily)
      for 6 days. Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg I.V.,
      followed 24 hours later by oral dexamethasone (8 mg once daily) in one arm, and
      oral dexamethasone and dolasetron in the other, also for 6 days. In arms 4, 5,
      and 6, ondansetron (32 mg I.V. or 8 mg orally twice daily) was administered in a
      similar manner to arms 1, 2, and 3 before and 24 hours after chemotherapy. Mean
      nausea severity (MNS) was assessed on a visual analog scale (VAS) in a daily
      diary. RESULTS: Of 703 patients enrolled, 696 were eligible. There were 343
      dolasetron- and 353 ondansetron-treated patients; 57% of dolasetron-treated
      patients had complete protection in the first 24 hours versus 67% of patients who
      received ondansetron (P = .013). MNS was also more pronounced on the dolasetron
      arm (P = .051). Sixty-seven percent of patients who received added dexamethasone
      in the first 24 hours had complete protection, compared with 55% without
      dexamethasone (P < .001). MNS was significantly reduced with the addition of
      dexamethasone (P < .001). At 7 days, dolasetron and ondansetron had equivalent
      complete protection rates (36% and 39%, respectively). With the addition of
      dexamethasone, 48% of patients compared with 28% had complete protection (P <
      .001). MNS was significantly improved with added dexamethasone (P < .001).
      CONCLUSION: At the doses used, dolasetron was significantly less effective than
      ondansetron at controlling nausea and vomiting in the first 24 hours in patients
      receiving moderately emetogenic chemotherapy, but there was no demonstrable
      difference between both drugs over 7 days. The addition of dexamethasone
      significantly improved the efficacy of both drugs in the first 24 hours and over
      7 days.

PMID- 9256144
TI  - Clinical practice guidelines for the treatment of unresectable non-small-cell
      lung cancer. Adopted on May 16, 1997 by the American Society of Clinical
      Oncology.
AB  - PURPOSE: The primary objective was to determine clinical practice guidelines for
      the diagnostic evaluation, treatment, and follow-up care of patients with
      surgically unresectable stage III and IV non-small-cell lung cancer (NSCLC).
      These guidelines are intended for use by oncologists in the care of patients
      outside of clinical trials. METHODS: An expert multidisciplinary Panel reviewed
      pertinent information from the published literature through April 1997; certain
      investigators were contacted for more recent and, in some cases, unpublished
      information. A computerized search was performed of MEDLINE data; directed
      searches based on the bibliographies of primary articles were also performed.
      Values for levels/grades of evidence were assigned by expert reviewers and
      approved by the Panel. Expert consensus was used for issues in which published
      data were insufficient. The options considered included the appropriate
      diagnostic evaluation of patients; the role of chemotherapy, radiation, and
      surgery; and strategies for follow-up care and lifestyle changes. The significant
      health outcomes considered in making the clinical practice guidelines included
      survival (disease-free and overall), quality of life, toxicity (both short- and
      long-term), and cost-effectiveness. An intervention or strategy was assigned
      benefit if it led to favorable changes in the outcomes listed. Harms considered
      were inappropriate disease management and excess cost without definable benefit.
      Costs were considered but were never the sole determinant for a recommendation.
      The guidelines underwent external review by selected physicians and a cancer
      quality-of-life expert, by Health Services Research Committee members, and by the
      American Society of Clinical Oncology (ASCO) Board of Directors. RESULTS AND
      CONCLUSIONS: In patients without evidence of extrathoracic cancer, a chest x-ray
      and chest computed axial tomography (CAT) scan are recommended to stage
      locoregional disease, with biopsy of mediastinal lymph nodes found on CAT scan to
      be greater than 1 cm in shortest transverse diameter. Pretreatment bone scan and
      head CAT scan are recommended only when signs or symptoms of disease are present.
      If a patient is otherwise potentially resectable, a biopsy should be performed of
      a radiographically documented isolated adrenal or hepatic mass to rule out
      metastatic disease. Chemotherapy, ideally a platinum-based regimen, is
      appropriate for selected patients who have a good performance status with both
      unresectable, locally advanced, and metastatic NSCLC. A detrimental effect on
      survival was observed with older alkylating agent-based regimens. In patients
      with unresectable stage III NSCLC, two or more cycles of cisplatin-based
      chemotherapy with or followed by radiation has been proven to enhance survival;
      ongoing maintenance chemotherapy is of unproven benefit. Chemotherapy should be
      administered for no more than eight cycles in patients with stage III or IV
      NSCLC. Initial treatment with an investigational agent is appropriate, provided a
      standard regimen is then given if the disease does not respond after two cycles.
      Delaying chemotherapy until symptoms develop may negate the survival benefits of
      treatment. There is no current evidence that either confirms or refutes that
      second-line chemotherapy improves survival in patients with nonresponding or
      progressive NSCLC. NSCLC histologic type is not an important prognostic factor in
      these patients, and the role of newer prognostic factors (eg, p53 mutation) in
      clinical decision-making is investigational. Radiation should be included as part
      of the standard treatment for selected patients with unresectable stage III
      NSCLC, whose performance status and pulmonary function are adequate. Definitive
      dose thoracic radiotherapy should be no less than 60 Gy in 1.8- to 2-Gy
      fractions. Local symptoms from primary or metastatic NSCLC can be relieved by
      judicious use of radiotherapy. (ABSTRACT TRUNCATED)

PMID- 9256143
TI  - Clinical impact of chemotherapy dose escalation in patients with hematologic
      malignancies and solid tumors.
AB  - PURPOSE: To review published controlled clinical trials examining the benefit of
      escalated chemotherapy in patients with hematologic and solid malignancies.
      METHODS: Studies were obtained by searching Medline and CancerLit and by review
      of bibliographies of published trials. We reviewed studies that examined dose
      intense (DI) chemotherapy alone, in combination with hematopoietic colony
      stimulating factors (CSFs), or high-dose therapy (HDT) with autologous bone
      marrow support (ABMT). RESULTS: DI therapy without CSF or ABMT has not been shown
      to improve overall outcome in any tumor except consolidative therapy of acute
      myelogenous leukemia (AML). In solid tumors, many published studies suggest that
      less than standard-intensity chemotherapy is suboptimal, but few studies that
      examined higher compared with standard-dose therapy have shown a significant
      difference in outcome. No studies have convincingly demonstrated improved overall
      survival (OS) with DI therapy with CSF support. The use of HDT with ABMT has been
      shown to improve survival in multiple myeloma (MM), as well as relapsed
      intermediate- and high-grade non-Hodgkin's lymphoma (NHL). High-dose chemotherapy
      with ABMT is promising in patients with metastatic breast cancer (MBC), but it
      should not yet be considered a standard approach for these patients. CONCLUSION:
      DI chemotherapy is an acceptable and standard therapeutic maneuver for patients
      with AML in first remission, MM, and relapsed aggressive NHL. In solid tumors,
      the use of DI chemotherapy either alone or with cytokine support has not been
      shown to improve outcome and should not be considered standard therapy. Current
      randomized trials should provide definitive answers about the role of DI therapy
      in solid tumors.

PMID- 9256145
TI  - CNS metastases: one's too many.

PMID- 9256146
TI  - Comparing an apple to a fruit salad.

PMID- 9256147
TI  - Hodgkin's disease failures: incorporating radiotherapy and high-dose treatment.

PMID- 9256148
TI  - Prospective randomized studies are needed to define the role of axillary lymph
      node dissection in primary breast cancer.

PMID- 9256150
TI  - Cutaneous melanoma, staging system.

PMID- 9256149
TI  - Can prophylactic CNS radiotherapy be omitted in high-risk childhood acute
      lymphoblastic leukemia?

PMID- 9256151
TI  - Ca2+ transient, cell volume, and microviscosity of the plasma membrane in smooth
      muscle.
AB  - Despite pronounced differences by which membrane-depolarizing or phospholipase C
      activating stimuli initiate contractile responses, a rise in [Ca2+]i is
      considered the primary mechanism for induction of smooth muscle contractions.
      Subsequent to the formation of the well-characterized Ca(2+)4-calmodulin complex,
      interaction with the catalytic subunit of myosin light chain kinase triggers
      phosphorylation of 20 kDa myosin light chain and activates actin-dependent Mg2+
      ATPase activity, which ultimately leads to the development of tension. The
      present article reviews the fundamental mechanisms leading to an increase in
      [Ca2+]i and discusses the biochemical processes involved in the transient and
      sustained phases of contraction. Moreover, the commentary summarizes current
      knowledge on the modulatory effect of changes in the microviscosity of the plasma
      membrane on the Ca2+ transient as well as the contractile response of smooth
      muscle. Evidence has accumulated that these changes in microviscosity alter the
      activity of membrane-bound enzymes and affect the generation of endogenous
      mediators responsible for the regulation of cytosolic Ca2+ concentrations and for
      the [Ca2+]i-sensitivity of myosin light chain phosphorylation.

PMID- 9256152
TI  - Alteration of hepatic microcirculation by oxethazaine and some vasoconstrictors
      in the perfused rat liver.
AB  - We previously reported that, in isolated perfused rat livers in a constant flow
      system, oxethazaine (OXZ) rapidly increased portal pressure (PP) accompanied by
      inhibition of oxygen uptake and the subsequent metabolic effects. In this study,
      hemodynamic changes were studied by using an indicator dilution technique and by
      microscopic observation of post-fixed liver samples stained with acridine orange
      or trapped fluorescence microspheres (FMSs). During the increase in PP induced by
      OXZ, the mean transit times of both red blood cells and azoalbumin were shortened
      markedly, and the vascular and extravascular albumin spaces decreased to 55 and
      18% of the controls, respectively. With acridine orange, in the control livers,
      all the dye infused was taken up and the periportal zones were uniformly stained
      over all the liver sections, whereas in the OXZ-treated livers, about 30% of the
      dye drained out, and extensive staining was observed in the central portion of
      the liver mass, but the peripheral portions of the liver were much less stained.
      The staining was often localized around large portal vein branches and spread
      toward the hepatic veins. These changes were recoverable in the absence of OXZ.
      Distributions of 1-microm and 15-microm FMSs were likewise altered by OXZ. Thus,
      uneven perfusion may be the primary cause of decreased tissue spaces and also of
      the metabolic effects produced by OXZ. Endothelin 1 also produced OXZ-like
      changes, while U-46619 had lesser effects. The methodology used in this study may
      help delineate the hepatic perfusion disturbance caused by various
      vasoconstrictors.

PMID- 9256153
TI  - Interaction of combinations of drugs, chemosensitizers, and peptides with the P
      glycoprotein multidrug transporter.
AB  - P-Glycoprotein functions as an ATP-driven efflux pump for hydrophobic natural
      products and peptides, and gives rise to resistance to multiple chemotherapeutic
      drugs. The inhibition of colchicine transport via P-glycoprotein by various
      compounds was determined in a plasma membrane vesicle model system. A
      chemotherapeutic drug (vinblastine) and several chemosensitizers (verapamil,
      reserpine, cyclosporin A) and hydrophobic peptides (N-acetyl-leucyl-leucyl
      methioninal, leupeptin, pepstatin A, valinomycin) were examined, both as
      individual species and as combinations of compounds. The median effect analysis
      was used to determine the concentration of each combination required to produce a
      median effect, Dm, as well as the sigmoidicity of the concentration-effect plot,
      m. The combination of cyclosporin A and verapamil was the only one established to
      be mutually nonexclusive, whereas several mutually exclusive pairs of compounds
      were identified. The combination index, CI, was calculated for several
      combinations of drugs, chemosensitizers, and peptides, and used to ascertain
      whether effects were synergistic, antagonistic, or additive. Some combinations
      (vinblastine/verapamil; verapamil/valinomycin) showed antagonism over the entire
      concentration range. Other combinations (valinomycin/N-acetyl-leucyl-leucyl
      methioninal; cyclosporin A/verapamil) displayed both synergism and antagonism
      over different regions of the CI plot. Many combinations of compounds displayed
      additive interactions over most of the CI plot. The median effect analysis may be
      helpful in identifying potentially useful additive or synergistic combinations of
      compounds for reversal of Pgp-mediated drug resistance.

PMID- 9256154
TI  - Alteration in neurofilament axonal transport in the sciatic nerve of the
      diisopropyl phosphorofluoridate (DFP)-treated hen.
AB  - Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester that produces
      organophosphorus ester-induced delayed neurotoxicity (OPIDN) in hens 7-14 days
      after a single s.c. dose of 1.7 mg/kg. In this study, hens were treated with a
      single dose of DFP (1.7 mg/kg, s.c.) 24 hr after [35S]methionine injection into
      the sacrolumbar region of their spinal cord, and killed 3, 7, 14, or 27 days post
      DFP treatment. The rates of transport of labeled high (NF-H), medium (NF-M), and
      low (NF-L) molecular weight neurofilaments, and tubulin were faster in DFP
      treated birds than in controls after 3 days. Subsequently, the rate of transport
      of these proteins started falling, so that the peaks of labeled proteins in
      control and DFP-treated hens were overlapping after 7 days. At 14 days, the peaks
      of NF-H, NF-M, and NF-L in treated hens were distinctly behind the corresponding
      peaks in control hens. This was again followed by an increase in transport of NF
      H and NF-L, but not of NF-M, so that the labeled NF-H and NF-L showed the same
      pattern in control and treated hens after 27 days. The transient decrease in NF-H
      and NF-L axonal transport rate, and recovery correlated in a temporal manner with
      the previously reported increase of Ca2+/calmodulin-dependent protein kinase
      mediated phosphorylation of neurofilament proteins and inhibition of calpain
      activity in the sciatic nerve in OPIDN. Proteinase inhibition has been reported
      recently to result in enhanced phosphorylation of neurofilaments in some cells.
      The present study suggests that the enhanced phosphorylation of neurofilaments by
      DFP-increased Ca2+/calmodulin-dependent protein kinase activity may be
      contributing toward alteration in NF axonal transport and the development of
      OPIDN.

PMID- 9256155
TI  - Effects of calcitriol and its analogues, calcipotriol (MC 903) and 20-epi
      1alpha,25-dihydroxyvitamin D3 (MC 1288), on calcium influx and DNA synthesis in
      cultured muscle cells.
AB  - The fast actions of the secosteroid hormone 1alpha,25-dihydroxyvitamin D3
      [1,25(OH)2D3; calcitriol] and the synthetic analogues calcipotriol (MC 903) and
      20-epi-1alpha,25(OH)2D3 (MC 1288) on cell calcium influx were compared in rat
      duodenum enterocytes as well as in cells from chick embryo skeletal muscle
      (myoblasts) and heart (myocytes), at various concentrations (10(-12) to 10(-8) M)
      and treatment intervals (1-10 min). In enterocytes, at a concentration of 10(-11)
      M, MC 1288 was significantly more active than 1,25(OH)2D3 in rapidly stimulating
      45Ca2+ uptake by enterocytes (80 vs 38% above controls, respectively), whereas MC
      903 was devoid of activity. However, calcipotriol increased Ca2+ influx in
      myocytes and myoblasts to a greater extent than the natural hormone, whereas MC
      1288 was more active only in myoblasts. Analogously to 1,25(OH)2D3, the fast MC
      903- and MC 1288-induced stimulation of 45Ca2+ uptake in enterocytes and muscle
      cells could be blocked by both verapamil and nifedipine. In addition, MC 903 and
      MC 1288 were more effective than 1,25(OH)2D3 in stimulating DNA synthesis in
      proliferating myoblasts and in inhibiting DNA synthesis in differentiating
      myoblasts. The results suggest, therefore, that modifications in the side-chain
      of the 1,25(OH)2D3 molecule increase its ability to modulate muscle cell Ca2+
      metabolism and growth. These findings are potentially relevant for the
      development of analogues for the treatment of vitamin D-dependent myopathies.

PMID- 9256156
TI  - Enhanced oral absorption and antiviral activity of 1-O-octadecyl-sn-glycero-3
      phospho-acyclovir and related compounds in hepatitis B virus infection, in vitro.
AB  - Acyclovir (ACV) triphosphate and azidothymidine (AZT) triphosphate inhibit the
      DNA polymerase of human hepatitis B virus (HBV) by 50% at submicromolar
      concentrations, but no effects of ACV or AZT treatment have been noted on the
      clinical manifestations of hepatitis B. We synthesized 1-O-octadecyl-sn-glycero-3
      phospho-acyclovir (ODG-P-ACV), 1-O-hexadecylpropanediol-3-phospho-acyclovir (HDP
      P-ACV), and 1-O-octadecyl-sn-glycero-3-phospho-azidothymidine (ODG-P-AZT), and
      evaluated their antiviral activity in human hepatoma cells that constitutively
      produce HBV (2.2.15 cells). ACV and AZT up to 100 microM caused only slight
      inhibition of HBV replication in 2.2.15 cells. However, HDP-P-ACV and ODG-P-ACV
      inhibited viral replication by 50% at 0.5 and 6.8 microM, respectively. ODG-P-AZT
      also showed increased antiviral activity, with a 50% reduction in HBV replication
      at 2.1 microM. Based on the EC50, HDP-P-ACV, ODG-P-ACV, and ODG-P-AZT were > 200,
      > 14.7, and > 48 times more active than their free nucleosides in reducing HBV
      replication in 2.2.15 cells. To evaluate the biochemical basis for the increased
      antiviral activity, we studied the uptake and metabolism of 1-O-octadecyl-sn
      glycero-3-phospho-[3H]acyclovir (ODG-P-[3H]ACV) in HepG2 cells. Cellular uptake
      of ODG-P-[3H]ACV was found to be substantially greater than that of [3H]ACV, and
      cellular levels of ACV-mono-, -di-, and -triphosphate were much higher with ODG-P
      ACV. ODG-P-[3H]ACV was well absorbed orally. Based on urinary recovery of tritium
      after oral or parenteral administration of the radiolabeled compounds, oral
      absorption of ODG-P-ACV in mice was 100% versus 37% for ACV. ODG-P-ACV plasma
      area under the curve was more than 7-fold greater than that of ACV. Lipid
      prodrugs of this type may be useful orally in treating viral diseases.

PMID- 9256157
TI  - Tyrosine phosphorylation of phosphatidylinositol 3-kinase and of the thromboxane
      A2 (TXA2) receptor by the TXA2 mimetic I-BOP in A7r5 cells.
AB  - Thromboxane A2 (TXA2) interacts with its G-protein coupled receptor, the TP
      receptor, to produce contraction and proliferation of vascular smooth muscle
      cells. We have shown previously that proliferation of primary cultures of
      vascular smooth muscle cells initiated by [1S-(1alpha, 2beta(5Z), 3alpha(1E, 3R),
      4alpha]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxab icyclo-[2.2.1]heptan
      2yl]-5'-heptenoic acid (I-BOP), a stable TXA2 mimetic, is mediated by activation
      of mitogen-activated protein (MAP) kinase. In the present study, we examined
      further the intracellular mediators involved in TXA2 activation of vascular
      smooth muscle cells. Transient transfection of the cDNA for the TP receptor into
      A7r5 vascular smooth muscle cells resulted in expression of TP receptors with a
      receptor density, Bmax, of 0.7 +/- 0.2 pmol/mg protein and a receptor affinity,
      Kd, of 0.6 +/- 0.1 nM (N = 7). Mock transfected cells lacked significant receptor
      expression. In TP receptor transfected cells, I-BOP increased the activation of
      MAP kinase 2-fold, stimulated tyrosine phosphorylation of cellular proteins of
      relative molecular mass (Mr) of 140, 85, 60, 56, and 45 kDa, and increased the
      message for c-jun, a nuclear transcription factor involved in mitogenesis, 2.6
      fold. Immunoblot analysis indicated that the 85-kDa protein represented
      phosphoinositide 3-kinase (PI3-K), while the 60 kDa protein was the TP receptor.
      The activity of PI3-K was increased 3.5-fold by the addition of I-BOP (0.1
      microM). In summary, the present study demonstrated that stimulation of the TP
      receptor results in tyrosine phosphorylation of the receptor and of PI3-K.

PMID- 9256158
TI  - Protein tyrosine kinase involvement in the production of superoxide anion by
      neutrophils exposed to Aroclor 1242, a mixture of polychlorinated biphenyls.
AB  - Neutrophils produce superoxide anion (O2-) when exposed in vitro to Aroclor 1242,
      a mixture of polychlorinated biphenyls (PCBs). The mechanism for this effect
      shares some similarities with the mechanism by which the physiologic agonist f
      Met-Leu-Phe (fMLP) activates neutrophils. Since production of O2- in response to
      fMLP involves GTP-binding proteins and protein tyrosine kinases (PTKs), the
      current study was undertaken to determine whether these signalling pathways are
      involved in PCB-induced neutrophil activation. Neutrophils exposed to Aroclor
      1242 or fMLP produced significant O2-. Pretreatment of intact neutrophils with
      pertussis toxin or cholera toxin or exposure of permeabilized cells to GDPbetaS
      significantly inhibited O2- production in fMLP-treated neutrophils but did not
      alter the response to Aroclor 1242. Pretreatment with genistein, an inhibitor of
      PTKs, significantly inhibited O2- production in both Aroclor 1242- and fMLP
      treated neutrophils; however, daidzein, a structural analogue of genistein which
      lacks activity against PTKs, was without effect. Exposure of neutrophils to
      Aroclor 1242 resulted in an increase within 1 min in tyrosine phosphorylation of
      proteins in the 40 and 60 kDa molecular mass ranges which persisted for up to 10
      min. Similar results were obtained with 2,2',4,4'-tetrachlorobiphenyl (2,2',4,4'
      TCB), a PCB congener that stimulates O2- production. In contrast, 3,3',4,4',5
      pentachlorobiphenyl (3,3',4,4',5-PeCB), a congener that does not generate O2-,
      caused only a transient increase in tyrosine phosphorylation of proteins in the
      40 kDa range with no effect on 60 kDa proteins. These data suggest that Aroclor
      1242 activates neutrophils to produce O2- by a mechanism that requires tyrosine
      kinase activity; however, heterotrimeric G-proteins are not likely to be
      involved.

PMID- 9256159
TI  - Characterization of a Chinese hamster ovary cell line with acquired resistance to
      the bisdioxopiperazine dexrazoxane (ICRF-187) catalytic inhibitor of
      topoisomerase II.
AB  - A Chinese hamster ovary (CHO) cell line highly resistant to the non-cleavable
      complex-forming topoisomerase II inhibitor dexrazoxane (ICRF-187, Zinecard) was
      selected. The resistant cell line (DZR) was 1500-fold resistant (IC50 = 2800 vs
      1.8 microM) to continuous dexrazoxane exposure. DZR cells were also cross
      resistant (8- to 500-fold) to other bisdioxopiperazines (ICRF-193, ICRF-154, and
      ICRF-186), and somewhat cross-resistant (4- to 14-fold) to anthracyclines
      (daunorubicin, doxorubicin, epirubicin, and idarubicin) and etoposide (8.5-fold),
      but not to the other non-cleavable complex-forming topoisomerase II inhibitors
      suramin and merbarone. The cytotoxicity of dexrazoxane to both cell lines was
      unchanged in the presence of the membrane-active agent verapamil. DZR cells were
      9-fold resistant to dexrazoxane-mediated inhibition of topoisomerase II DNA
      decatenation activity compared with CHO cells (IC50 = 400 vs 45 microM), but were
      only 1.4-fold (IC50 = 110 vs 83 microM) resistant to etoposide. DZR cells
      contained one-half the level of topoisomerase II protein compared with parental
      CHO cells. However, the specific activity for decatenation using nuclear extract
      topoisomerase II was unchanged. Etoposide (100 microM)-induced topoisomerase II
      DNA complexes in DZR cells and isolated nuclei were similarly one-half the level
      found in CHO cells and in isolated nuclei. However, the ability of 500 microM
      dexrazoxane to inhibit etoposide (100 microM)-induced topoisomerase II-DNA
      covalent complexes was reduced 4- to 6-fold in both DZR cells and nuclei compared
      with CHO cells and nuclei. In contrast, there was no differential ability of
      aclarubicin or merbarone to inhibit etoposide-induced topoisomerase II-DNA
      complexes in CHO compared with DZR cells and isolated nuclei. It was concluded
      that the DZR cell line acquired its resistance to dexrazoxane mainly through an
      alteration in the topoisomerase II target.

PMID- 9256161
TI  - Dietary calcium supplementation and dopamine-beta-hydroxylase in spontaneously
      hypertensive rats.
AB  - Spontaneously hypertensive 4-week-old male rats were fed, before and after the
      onset of hypertension, with either commercial chow (control) or commercial chow
      combined with different forms of milk proteins with or without calcium
      supplementation. After 40 weeks, rats were still hypertensive, and dopamine-beta
      hydroxylase enzyme activity measured simultaneously in serum and adrenal was
      found to be higher than in the controls. The enzyme activity in rats fed diets
      with milk proteins was increased significantly in both serum and adrenal compared
      with the control, and such enhancement was significantly higher than that
      observed in animals fed the commercial diet supplemented with calcium (1.2%),
      suggesting that dietary calcium intake associated with dietary protein of high
      digestibility, such as casein, potentiates the endogenous mechanisms regulating
      the homeostasis of calcium more than calcium supplementation itself. Moreover,
      the selective and additive effect of diets supplemented with milk proteins and
      calcium on adrenal enzyme activity clearly suggests a relationship between
      cardiovascular diseases involving the genesis of hypertension and stress
      mechanisms through the hypothalamo-pituitary adreno-sympathetic axis.

PMID- 9256160
TI  - Cross-resistance to antifolates in multidrug resistant cell lines with P
      glycoprotein or multidrug resistance protein expression.
AB  - Resistance to some (lipophilic) antifolates has been associated with P
      glycoprotein (P-gp)-mediated multidrug resistance (MDR). A possible relationship
      with non-P-gp MDR has not been established. We studied resistance to antifolates
      in SW-1573 human lung carcinoma cells, a P-gp overexpressing variant SW
      1573/2R160 and a multidrug resistance protein (MRP) overexpressing variant SW
      1573/2R120. In this study, thymidylate synthase (TS) inhibitors with different
      properties concerning the efficiency of membrane transport and the efficiency of
      polyglutamylation were tested for cross-resistance in SW-1573/2R120 and SW
      1573/2R160 cells. Growth inhibition patterns in this cell line panel were
      measured by the Sulforhodamine B (SRB) assay. Resistance factors for TS
      inhibitors were: 2.4 and 0.4 for 5-fluorouracil (5FU), 18.8 and 8.8 for ZD1694,
      17 and 0.7 for AG337, and 40 and 8.3 for BW1843U89 in SW-1573/2R160 and SW
      1573/2R120, respectively. This study showed changes in the TS enzyme kinetics
      during the induction of doxorubicin resistance in both SW-1573 variants,
      resulting in 2-fold lower Km values for 2'-deoxyuridine-5'-monophosphate (dUMP)
      in both resistant variants compared to the parental cell line. TS activity, TS
      protein induction and TS mRNA expression all had 2-fold increased in the SW
      1573/2R120 compared to the SW-1573/2R160. 3H-MTX influx was 2-fold lower in SW
      1573/2R160 cells compared to SW-1573/2R120 and SW-1573 cells. In the SW
      1573/2R160 cell line, an aberrant intracellular trafficking towards the target TS
      was observed, compared to SW-1573/2R120 and SW-1573 cells as measured by the TS
      in situ assay. The rate of TS inhibition by the TS inhibitors used in this study
      was similar in all cell lines. In conclusion, collateral sensitivity to 5FU and
      the lipophilic AG337 and cross-resistance to other antifolates were observed in
      non-P-gp MDR SW-1573/2R120 cells, as well as resistance to all antifolates in P
      gp SW-1573/2R160 cells. The mechanism of resistance in SW-1573/2R160 cells
      possibly involves reduced influx and changes in intracellular trafficking routes.
      For the SW-1573/2R120 cell line, several changes related to the TS enzyme
      possibly play a role in the observed cross-resistance and collateral sensitivity
      pattern.

PMID- 9256162
TI  - Inhibition of calcium-induced insulin secretion from intact HIT-T15 or INS-1 beta
      cells by GTP depletion.
AB  - Using intact rat islets, we previously observed that GTP depletion (achieved
      through the use of mycophenolic acid or other synthesis inhibitors) impedes
      nutrient- but not K+-induced insulin secretion. It was concluded that a proximal
      nutrient-dependent step in stimulus-secretion coupling (but not the process of
      Ca2+-induced exocytosis itself) is modulated by ambient GTP levels. To examine
      Ca2+-dependent steps further in intact beta cells, INS-1 cells (which synthesize
      GTP and ATP similarly to rat islets) and HIT-T15 cells (whose synthesis of purine
      nucleotides is different) were studied following cell culture for 1-18 hr in
      various concentrations of mycophenolic acid (MPA) or mizoribine (MZ). Both agents
      profoundly reduced GTP content (mean: -78%) and lowered the GTP/GDP ratio by an
      average of -73%; concomitantly, MPA or MZ reduced insulin secretion induced by 10
      mM glucose, 30 or 40 mM KCl, or 100 microM tolbutamide, independent of any
      changes in cell viability, insulin content, ATP content, the ATP/ADP ratio, or
      cytosolic free Ca2+ concentrations. In INS-1 cells (which appear to have normal
      nucleobase transport and "salvage" pathway activities), guanine (but not adenine)
      restored GTP content, the GTP/GDP ratio, and Ca2+-induced secretion. In HIT
      cells, the phosphoribosylation of exogenous guanine or hypoxanthine is defective;
      however, provision of 500 microM guanosine (but not adenosine) reversed the
      effects of MPA. We conclude that, at least in certain situations, a requisite
      role for GTP in the distal step(s) of exocytosis can be demonstrated.

PMID- 9256163
TI  - Beta-adrenergic regulation of renin expression in differentiated U-937 monocytic
      cells.
AB  - Previous studies from our laboratories demonstrated that human decidual
      macrophages and peripheral mononuclear cells express renin. In the present study,
      we found that U-937 monocytes, induced to differentiate into macrophage-like
      cells by treatment with phorbol dibutyrate (PDBU), express renin mRNA and release
      renin (95%, of which is in the form of prorenin). Treatment of these PDBU-exposed
      cells with dibutyryl-cAMP (1 mM) caused a 20-fold increase in renin mRNA and a 10
      fold increase in prorenin release. Forskolin (10 microM), an activator of
      adenylyl cyclase, and terbutaline (100 microM), a beta2-adrenergic agonist known
      to increase cAMP levels, also increased renin mRNA and prorenin release. The
      secretory response to terbutaline was potentiated by the type IV cyclic AMP
      phosphodiesterase (PDE) inhibitor Ro 20-1724 (50 microM). Angiotensin II agonist
      inhibited the stimulatory effect of terbutaline on renin secretion as did the
      cytokines tumor necrosis factor-alpha and lipopolysaccharide plus interferon
      gamma. Since other studies have shown that U-937 cells possess beta2-adrenergic
      receptors and express mainly the type IV PDE, the present findings strongly
      suggest that beta-adrenergic receptors in mononuclear cells are coupled to renin
      expression via the cAMP transduction pathway. The results support a possible role
      for the renin-angiotensin system in macrophage function and suggest potential
      autocrine regulatory mechanisms in prorenin expression.

PMID- 9256164
TI  - Binding of mercury in renal brush-border and basolateral membrane-vesicles.
AB  - The influence of the thiols L-cysteine (CYS), glutathione (GSH), and 2,3
      dimercapto-1-propanesulfonate (DMPS) on the binding and transport of inorganic
      mercury (Hg2+) in luminal (brush-border) and basolateral membrane-vesicles
      isolated from the kidneys of rats was studied using radiolabeled mercury
      (203HgCl2). Membrane-vesicles were exposed to 1, 10, or 100 microM Hg2+ in the
      presence or absence of a 3:1 or 10:1 mole-ratio of CYS, GSH, or DMPS relative to
      Hg2+. Equilibration of mercury with the membrane-vesicles occurred very rapidly,
      essentially being complete within 5 sec. By 60 sec, binding accounted for 87-97%
      of intravesicular Hg2+ in the absence of exogenous thiols. All three thiols
      significantly reduced the fraction of binding, with DMPS being the most effective
      agent. CYS enhanced the association of Hg2+ with luminal membrane-vesicles
      relative to that when Hg2+ was added alone, suggesting that conjugation of Hg2+
      with CYS promotes the transport of low concentrations of Hg2+. In contrast, an
      excess of either GSH or DMPS relative to Hg2+ interfered significantly with both
      the binding and transport of Hg2+ into either luminal or basolateral membrane
      vesicles. In summary, the present study is the first to describe the association
      of Hg2+ with renal luminal and basolateral membrane-vesicles. Evidence was
      obtained for the involvement of a Hg2+-CYS conjugate as a mechanism by which Hg2+
      uptake and binding to luminal membranes occur and for an inhibitory effect of GSH
      and the chelator DMPS with regard to Hg2+ uptake and binding, demonstrating that
      extracellular thiols can modulate significantly the renal accumulation of Hg2+.

PMID- 9256165
TI  - Inhibition of extracellular release of proinflammatory secretory phospholipase A2
      (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity.
AB  - Sulfasalazine is widely used in rheumatoid arthritis and inflammatory bowel
      diseases. The mechanisms of its activity have not been elucidated. In leukocytes,
      sulfasalazine and its analogue, CL 42A, inhibited the formation of leukotrienes
      and possibly of the second messenger compounds at the level of phospholipase C.
      Partial inhibition of interleukin-lbeta (IL-1beta), IL-6 and tumor necrosis
      factor-alpha (TNF-alpha) was also found. Since the synthesis of eicosanoids is
      induced by phospholipase A2 and since secretory phospholipase A2 (sPLA2) is
      proinflammatory, we investigated the impact of sulfasalazine and related
      compounds on mRNA, protein synthesis, and release of sPLA2 from osteoblasts.
      Sulfasalazine and CL 42A markedly inhibited extracellular release of sPLA2. The
      impact of sulfasalazine was evident at 50 microM (P < 0.001) and maximal at 400
      microM, and that of CL 42A at 10 microM (P < 0.001) and 200 microM, respectively.
      Split products of sulfasalazine, 5-aminosalicylic acid (400 microM) and
      sulfapyridine (400 microM), had no impact. The effect of sulfasalazine and CL 42A
      was evident regardless of whether the cells were stimulated with IL-1beta/TNF
      alpha, lipopolysaccharide/forskolin, or dibutyryl-cAMP. Sulfasalazine and CL 42A
      did not alter the level of sPLA2 mRNA. Exposure of stimulated fetal rat calvaria
      osteoblasts (FRCO) to sulfasalazine did not show accumulation of the
      intracellular sPLA2 protein as tested by western blot; however, enzymatic
      activity of PLA2 in disrupted cells was definitely increased. Thus, the impact is
      on the post-transcriptional release of sPLA2 rather than on the synthesis. There
      was also an increase in the extracellular release of prostaglandin E2 from FRCO
      exposed to sulfasalazine or to CL 42A. In contrast, sulfasalazine had no effect
      on the extracellular release of gelatinase from the cells or on mRNA of cytosolic
      PLA2 or cyclooxygenase 2. We conclude that the anti-inflammatory activity of
      sulfasalazine may be related, in part, to the selective inhibition of the
      extracellular release of proinflammatory sPLA2.

PMID- 9256167
TI  - Time course of the effects of different cannabimimetics on prolactin and
      gonadotrophin secretion: evidence for the presence of CB1 receptors in
      hypothalamic structures and their involvement in the effects of cannabimimetics.
AB  - Several reports have demonstrated that (-)-delta9-tetrahydrocannabinol (delta9
      THC) and arachidonylethanolamide [anandamide (AEA)] were able to inhibit
      prolactin (PRL) secretion from the anterior pituitary gland in male rodents,
      whereas ovarian phase-dependent effects were seen in females. However, in most of
      these studies, the analysis of PRL levels was performed at times longer than 30
      min after cannabinoid administration. In the present study, we examined the time
      course of the effects of three different cannabimimetics, delta9-THC, AEA, and
      AM356 (R-methanandamide), a more stable analog of AEA, on PRL and gonadotrophin
      secretion in male Wistar rats. In addition, we characterized the presence of
      cannabinoid receptors in hypothalamic structures related to neuroendocrine
      control and studied their potential involvement in the effects of
      cannabimimetics. We found that the three compounds decreased plasma luteinizing
      hormone (LH) levels, although only the effects of delta9-THC were statistically
      significant. The inhibitory effect was already apparent at 40 min after
      administration, but only in the case of delta9-THC did it persist up to 180 min
      after administration. No significant changes were seen in plasma follicle
      stimulating hormone (FSH) levels after the administration of any of the three
      different cannabimimetics at any of the four times analyzed. Both AEA and AM356
      produced a significant decrease in plasma PRL levels, which appeared at 20 min
      after administration and persisted up to 60 min, waning after this time.
      Interestingly, the time course of the effect of delta9-THC resembled that of AEA
      and AM356 only during the later part of the response, because delta9-THC produced
      a marked increase in plasma PRL levels at 20 min, no changes at 40 min and a
      decrease from 60 min up to 180 min. In additional experiments, we tried to
      elucidate which of these two phases observed after delta9-THC administration was
      mediated by the activation of cannabinoid receptors. These receptors are present
      in hypothalamic structures related to neuroendocrine control, with the highest
      densities in the arcuate nucleus (dorsal area) and the medial preoptic area, and
      the lowest in the lateral hypothalamic area, although none of these regions
      exhibited high densities for this receptor as compared with classical regions
      containing cannabinoid receptors, such as the basal ganglia. The activation of
      these receptors by delta9-THC seems to be involved in the inhibitory phase of the
      effect of this cannabinoid on PRL release, but not in the early stimulation; when
      these receptors were blocked with a specific antagonist, SR141716, the
      stimulation by delta9-THC was still observed, but the late inhibition was
      abolished. In summary, AEA and AM356 markedly decreased PRL release and slightly
      decreased LH secretion, with no changes on FSH release. delta9-THC also produced
      a marked inhibition of LH secretion, but its effects on PRL were biphasic with an
      early stimulation not mediated by the activation of cannabinoid receptors,
      followed by a late and cannabinoid receptor-mediated inhibition. Their site of
      action may well be the hypothalamic structures related to neuroendocrine control,
      which contain a small, but probably very active, population of cannabinoid
      receptors.

PMID- 9256166
TI  - Functional expression of human intestinal Na+-dependent and Na+-independent
      nucleoside transporters in Xenopus laevis oocytes.
AB  - We have shown previously that the human jejunal brush border membrane expresses
      both the N1 (cif) and the N2 (cit) Na+-dependent (concentrative) nucleoside
      transporters but not the Na+-independent (facilitative)
      nitrobenzylmercaptopurineriboside (NBMPR)-sensitive (es) transporter (Patil SD
      and Unadkat JD, Am J Physiol, 272: 1314-1320, 1997). In the present study, we
      have demonstrated that when Xenopus laevis oocytes are microinjected with human
      jejunal mRNA, four nucleoside transporters are expressed simultaneously, namely
      the N1 and N2 Na+-dependent nucleoside transporters and the es and the NBMPR
      insensitive (ei) Na+-independent transporters. The expressed Na+-dependent
      nucleoside transporters showed substrate specificity identical to that previously
      described by us using jejunal brush border membrane vesicles (Patil SD and
      Unadkat JD, Am J Physiol, 272: 1314-1320, 1997). The expressed es and ei Na+
      independent transporters demonstrated broad substrate selectivity with both
      purines and pyrimidines capable of inhibiting the uptake of guanosine and
      thymidine mediated by this transporter. The expressed Na+-dependent nucleoside
      transporters mediated the transport of their respective nucleoside substrates
      with a high affinity and a low capacity, whereas the es and the ei transporters
      mediated the transport of nucleosides with a low affinity and a high capacity.
      Collectively, these observations suggest that the Na+-independent nucleoside
      transporters are expressed in the basolateral membrane of the human jejunal
      epithelium. Based on these data, we hypothesize that the concentrative
      transporters in the brush border membrane and equilibrative transporters in the
      basolateral membrane are arranged in series in the human jejunal epithelium to
      allow efficient vectorial transport of nucleosides from the lumen to the blood.
      The simultaneous expression of four nucleoside transporters in X. laevis oocytes
      establishes a basis for molecular cloning of these four human nucleoside
      transporters.

PMID- 9256168
TI  - Effect of wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
      (LY294002) on N-formyl-methionyl-leucyl-phenylalanine-induced phospholipase D
      activation in differentiated HL60 cells: possible involvement of
      phosphatidylinositol 3-kinase in phospholipase D activation.
AB  - Phospholipase D (PLD) plays an important role in neutrophil activation. However,
      despite various proposed mechanisms, its detailed regulatory mechanism is not
      fully understood. The functional coupling between phosphatidylinositol 3-kinase
      (PI 3-kinase) and PLD was investigated in N-formyl-methionyl-leucyl-phenylalanine
      (fMLP)-stimulated human promyelocytic leukemia HL60 cells, using wortmannin, a
      fungal metabolite that is known as a selective inhibitor for phosphatidylinositol
      3-kinase. Treatment of cells with this drug inhibited the formation of both
      phosphatidylinositol 3,4,5-trisphosphate (PIP3), a product of PI 3-kinase, and
      phosphatidylbutanol (PBut), the specific product of transphosphatidylation due to
      PLD in the presence of butanol, with similar concentration dependence (IC50 = 30
      70 nM). Another PI 3-kinase inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran
      4-one (LY294002) also inhibited PBut formation in a concentration-dependent
      manner. However, wortmannin failed to inhibit phorbol 12-myristate 13-acetate
      induced PLD activation in whole cells and membrane PLD activity in an in vitro
      assay system, indicating that inhibition of fMLP-induced PLD activation by
      wortmannin was not due to its direct effect on PLD activity. These results
      suggest that a major part of inhibition of PLD activation by wortmannin might be
      mediated through its effect on PI 3-kinase.

PMID- 9256169
TI  - Specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl propyl) piperazine
      (GBR-12935), an inhibitor of the dopamine transporter, to human CYP2D6.
AB  - The binding of [3H]1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl propyl) piperazine
      (GBR-12935), an antagonist of the dopamine transporter, to human P450s expressed
      in yeast cells was investigated. Among the ten forms of human P450 tested
      (CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2D6, 2E1, and 3A4), [3H]GBR-12935 bound
      most strongly to CYP2D6. The calculated Kd of [3H]GBR-12935 binding to CYP2D6 was
      42.2 nM, indicating that GBR-12935 has a high affinity for CYP2D6. The
      characteristics of [3H]GBR-12935 binding to CYP2D6 were investigated by
      competitive studies using several chemicals. The binding of [3H]GBR-12935 to
      CYP2D6 was not changed by dopamine, suggesting that these binding sites are not
      dopamine-sensitive binding sites. The binding of [3H]GBR-12935 to CYP2D6 was
      decreased partially by substrates or inhibitors of CYP2D isoforms (quinine,
      quinidine, propranolol, bufuralol, imipramine, and desipramine). By means of
      binding studies using several forms of expressed human P450, we demonstrated that
      the CYP2D isoform is one GBR-12935 binding site that is insensitive to dopamine.

PMID- 9256170
TI  - Suppressive effects of tranilast on the expression of inducible cyclooxygenase
      (COX2) in interleukin-1beta-stimulated fibroblasts.
AB  - We investigated the effects of tranilast on inducible cyclooxygenase (COX2)
      mediated prostaglandin E2 (PGE2) production and enzyme induction in interleukin
      lbeta (IL-1beta)-stimulated cultured dermal fibroblasts. IL-1beta enhanced PGE2
      production in cultured fibroblasts. Tranilast did not affect constitutive
      cyclooxygenase (COX1) or COX2 activity in non-stimulated or IL-lbeta-stimulated
      fibroblasts. However, the COX2 expression induced by IL-1beta was inhibited by
      tranilast. This result, that IL-1beta-induced COX2 expression was suppressed by
      tranilast, was confirmed by immunohistochemical analysis. Thus, it is possible
      for tranilast to regulate PGE2 production by inhibiting COX2 induction.

PMID- 9256171
TI  - Insulin-like growth factor-I ameliorates delayed kidney graft function and the
      acute nephrotoxic effects of cyclosporine.
AB  - BACKGROUND: Delayed graft function (DGF) is a relatively common complication
      after cadaveric renal transplantation. The adverse effect of DGF on long-term
      graft survival has lead to intensive efforts to reduce ischemic graft injury. In
      this study we examined the effects of a new protective treatment based on insulin
      growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery
      and on the nephrotoxicity that is a common side effect of mainstream
      immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is
      effective in treating experimental ischemic renal failure, these peptides may be
      useful as perspective clinical treatments. METHODS: We have addressed three areas
      relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First,
      because of the immunogenic properties of IGF-I, we assessed the effect of des(1
      3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined
      whether treatment with des(1-3)IGF-I influences the early function of
      transplanted kidneys in a model of DGF induced by a combination of warm and cold
      ischemia. Finally we tested whether IGF-I protects against acute cyclosporine
      nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the
      skin grafts (P=0.57). The administration of this peptide in a model of syngenic
      renal transplant improved the early function of the graft. Postoperative values
      of creatinine and blood urea nitrogen were significantly better (P<0.05) in
      treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with
      better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In
      evaluating this study it should be recognized that the animal models studied,
      although widely used, differ from the human condition. However, IGF-I and des(1
      3)IGF-I exhibit properties that strongly suggest their value in preventing
      clinical DGF, and they deserve further studies.

PMID- 9256172
TI  - Cellular and molecular predictors of chronic renal dysfunction after initial
      ischemia/reperfusion injury of a single kidney.
AB  - BACKGROUND: Initial ischemia/reperfusion injury occurring secondary to organ
      retrieval, storage, and transplantation has been associated with late renal
      allograft deterioration and failure. In addition, there is an apparent synergy,
      reported in several clinical series, between the initial injuries of
      ischemia/reperfusion and acute rejection; the long-term results of graft survival
      are significantly deceased after both events in combination as compared with
      either alone or if no such episodes occur. METHODS: In the present study, we
      examined patterns of proteinuria, cellular infiltration, cytokine expression, and
      glomerulosclerosis over time in Lewis and Fischer 344 rats after 45 min of warm
      ischemia of a single kidney and with or without contralateral nephrectomy. Both
      early (4 hr to 7 days) and late (2-52 weeks) events were studied serially in the
      affected kidneys morphologically, by immunohistology and by reverse transcriptase
      polymerase chain reaction. RESULTS: Intercellular adhesion molecule 1,
      endothelin, and major histocompatibility complex class II expression were up
      regulated within 2 to 5 days after injury; T cells and macrophages increased
      transiently. Proteinuria developed after approximately 8 weeks only in animals
      bearing a single injured kidney, and not in those with a retained native organ.
      Progressive morphological changes occurred after 16 weeks, including
      glomerulosclerosis, arterial obliteration, and interstitial fibrosis. After a
      period of relative quiescence, expression of intercellular adhesion molecule 1
      again increased in relation to progressive macrophage infiltration and their
      associated products, particularly, interleukin 1, tumor necrosis factor-alpha,
      transforming growth factor-beta, and inducible nitric oxide synthase. Monocyte
      chemotactic protein 1 was intensely up-regulated by 24 weeks, coincident with a
      dramatic rise in this infiltrating population. These changes remained virtually
      at baseline in animals with a retained native kidney. CONCLUSIONS: These data
      imply that chronic injury after significant initial ischemia and reperfusion
      occurs when there is already a 50% renal mass reduction, but not when two kidneys
      remain in place. Permanent nephron loss resulting from such an insult could
      account for this phenomenon. Early ischemia and reperfusion, if severe enough in
      a single kidney, may be an important antigen-independent risk factor for later
      renal deterioration and failure. In the context of a renal allograft, it may
      contribute to chronic rejection.

PMID- 9256174
TI  - Efficacy of intraportal infusion of prostaglandin E1 to improve the hepatic blood
      flow and graft viability in porcine liver transplantation.
AB  - BACKGROUND: Prostaglandin E1 (PGE1) has been reported to have a protective effect
      in experimental and clinical models of liver damage. The aim of this study was to
      elucidate the effects of the intraportal infusion of PGE1 on hepatic blood flow
      and graft viability after orthotopic liver transplantation in pigs. METHODS:
      First, the hepatic arterial flow (HAF), portal venous flow (PVF), and liver
      tissue blood flow (LTBF) were measured during the continuous intravenous or
      intraportal infusion of PGE1. Second, two groups of pigs underwent orthotopic
      liver transplantation: group A, untreated controls; and group B, animals that
      received intraportal PGE1 for 2 hr after vascular reconstruction of the
      allograft. Changes in HAF, PVF, LTBF, and hepatic function were measured.
      RESULTS: The intraportal infusion of PGE1 significantly increased HAF and had no
      effect on blood pressure, PVF, or LTBF. In group B, HAF and LTBF increased
      significantly with time. In group A, HAF remained unchanged and a decrease in
      LTBF was observed. Group B exhibited a higher arterial ketone body ratio and a
      greater bile flow compared with group A. A significant elevation in serum
      glutamic oxaloacetic transaminase concentration was observed in group A, but not
      in group B. CONCLUSIONS: This study demonstrates that the intraportal infusion of
      PGE1 improves hepatic allograft blood flow, predominantly through an effect on
      HAF, and may improve graft viability after orthotopic liver transplantation.

PMID- 9256173
TI  - Changes in cell surface glycosylation in alpha1,3-galactosyltransferase knockout
      and alpha1,2-fucosyltransferase transgenic mice.
AB  - BACKGROUND: Inactivation of the alpha1,3-galactosyltransferase (GalT) gene by
      homologous recombination (knockout [KO] mice) and competition for the enzyme's N
      acetyllactosamine substrate by transgenically expressed alpha1,2
      fucosyltransferase (H-transferase) are two genetic approaches to elimination of
      the Gal alpha1,3Gal (alphaGal) epitope, which is the major xenoantigen in pigs
      against which humans have preformed antibodies. Such genetic manipulations often
      have unpredictable results. METHODS: A panel of 19 selected lectins was used to
      characterize the changes in cell surface glycosylation in GalT KO and H
      transferase transgenic mice, compared with nontransgenic littermate controls.
      RESULTS: GalT KO mice showed complete elimination of the alphaGal epitope, as
      reported previously. Surprisingly, however, this was associated with only a
      modest increase in N-acetyllactosamine residues and had little other effect on
      the pattern of lectin binding. In contrast, the pattern of lectin binding to H
      transferase transgenic mouse cells was more profoundly disturbed and indicated,
      in addition to the expected expression of H substance and suppression of the
      alphaGal epitope, that there was a marked reduction in alpha2,3-sialylation and
      exposure of the normally cryptic antigens, sialylated Tn and Forssman antigens.
      Similar changes in lectin reactivity with porcine aortic endothelial cells were
      induced by neuraminidase treatment. CONCLUSIONS: Lectins were able to bind
      underlying carbohydrate structures (sialylated Tn and Forssman antigens) that are
      normally cryptic antigens on H-transferase transgenic mouse spleen and cardiac
      endothelial cells, probably as a consequence of the reduction in the
      electronegativity of the cell surface due to reduced sialylation. As humans have
      preformed anti-Tn and anti-Forssman antibodies, it is possible that these
      structures may become targets of the xenograft rejection process, including
      hyperacute rejection.

PMID- 9256175
TI  - Characteristics of endothelin receptors in acutely rejecting transplanted lungs.
AB  - Experiments were designed to characterize endothelin receptors in bronchi and
      parenchyma of transplanted lungs during acute rejection. Third-order bronchi from
      autografted or allografted lungs were either cut into rings and suspended in
      organ chambers for the measurement of isometric force or frozen for isolation of
      membrane proteins. Lung parenchyma was prepared for histology or isolation of
      membrane protein. The grade of rejection was 2.74+/-0.17 (n= 19) in
      allotransplanted lungs; evidence of infection was present in 58% of the
      transplanted lungs. In organ chamber experiments, endothelin 1 (which stimulates
      endothelin A receptors) caused comparable contraction of bronchi from
      autotransplanted and allotransplanted rejecting lungs. Endothelin 3 (which
      stimulates endothelin A and B receptors) caused contractions of bronchi from
      autotransplanted lungs which were not different from those caused by endothelin
      1. In contrast, contractions caused by endothelin 3 were reduced in bronchi from
      rejecting allotransplanted lungs. The magnitude of contractions caused by
      endothelin 3 was reduced further when infection was present with rejection.
      Competitive inhibition of 125I-endothelin 1 by endothelin 3 was significant for a
      two-site binding model in membranes prepared from all bronchi and lung
      parenchyma. The total number of binding sites (Bmax) was reduced significantly in
      bronchi and parenchyma from rejecting lungs with or without infection. The
      relative proportions of high-affinity and low-affinity binding sites did not
      change. Affinities of both high- and low-affinity receptors were not altered with
      rejection. These results indicate that at least two subtypes of endothelin
      receptors are present on canine bronchial smooth muscle and parenchyma. The
      number of endothelin receptors associated with bronchial contractions is reduced
      with rejection of lung allografts.

PMID- 9256176
TI  - A new, biventricular working heterotopic heart transplant model: anatomic and
      physiologic considerations.
AB  - BACKGROUND: Current heterotopic heart transplant models have nonworking left
      ventricles that atrophy and are not suitable for some studies. We developed and
      characterized a new heterotopic model with working left and right ventricles.
      METHODS: Hemodynamics were compared in the working and nonworking models. The
      influence of the length of the donor's aorta on coronary arterial oxygenation was
      tested. The influence of the recipient's arterial pressure on developed left
      ventricular systolic pressure and the effects of alpha- and beta-adrenergic
      stimulation were examined in both models. The nonworking and working models were
      compared in chronic transplant preparations to investigate possible ventricular
      atrophy. RESULTS: In this model, coronary arterial oxygen tension was influenced
      by the length of the donor's aorta. With a short donor aorta (0.5 cm in the
      porcine model), normal coronary arterial oxygenation is maintained. Left
      ventricular systolic pressure was greater in the working compared with the
      nonworking models. Left ventricular systolic pressure did not respond to alpha
      adrenergic stimulation but did respond to beta-adrenergic and combined
      stimulation, which indicates its relationship to donor heart output. Left
      ventricular systolic pressure correlated with and was determined by recipient
      arterial pressure. Ventricular atrophy occurred in the nonworking model, but
      ventricular weight was maintained at sham control levels in this new working
      model. CONCLUSION: These results demonstrate the surgical anatomic considerations
      of a new heterotopic heart transplant model in which the left and right
      ventricles work. Its hemodynamic performance is related to recipient
      hemodynamics, and the model responds to adrenergic stimulation. In chronic
      studies, ventricular mass is maintained, thus allowing this model to overcome a
      significant shortcoming of existing heterotopic heart transplant models.

PMID- 9256177
TI  - Factors contributing to the development of chronic rejection in heterotopic rat
      heart transplantation.
AB  - BACKGROUND: The present study was devised to elucidate the influence of
      immunogenicity, immunosuppression, and ischemia on the development of transplant
      vasculopathy (TVP) as well as to investigate myointimal proliferation in
      syngeneic transplantation. METHODS: Fischer 344 and Brown Norway rat heart
      allografts and Lewis isografts were treated with rapamycin or cyclosporine,
      exposed to 4 hr of cold ischemia, and observed for 100 to 300 days before the
      incidence and degree of TVP and perivascular infiltration were assessed. RESULTS:
      The incidence of TVP in Fischer 344-->Lewis allografts (rapamycin, 0.5 mg/kg for
      14 days) rose steadily, with dense mononuclear infiltration present in coronary
      lesions at all times (from 10+/-2% at 50 days to 85+/-15% at 150 days). Increased
      immunogenicity (Brown Norway-->Lewis) intensified TVP (62+/-13%) as compared with
      its control (25+/-15%, P<0.005). Enhanced immunosuppression (rapamycin, 0.5 mg/kg
      daily) decreased the incidence of TVP (22+/-11%, P<0.005), and additional low
      dose cyclosporine was ineffective (1.5 mg/kg daily, 40+/-14%, NS). Four hours of
      cold ischemia before transplantation failed to have any effect on allografts, but
      promoted TVP in isografts (0 vs. 11+/-8%). CONCLUSIONS: The antigenic stimulus
      has probably the most important impact on the development of TVP, but is not
      necessarily essential. In most allografts, TVP probably reflects ongoing
      sublethal acute rejection, whereas myointimal proliferation in isografts
      presumably results from a perioperative antigen-independent response-to-injury
      mechanism.

PMID- 9256178
TI  - A new model for heterotopic aortic valve transplantation.
AB  - A new model for heterotopic aortic valve transplantation in the rat is described.
      A composite allograft with an intact aortic valve and partial mitral valve was
      harvested from 4-month-old (400-450 g) Long-Evans rats and grafted
      heterotopically into the abdominal aorta of 4-week-old (80-100 g) rats with an
      optimal size match. At the end of a 1-month observation period, all experimental
      animals were alive and all showed 100% patency of the aortic valve allografts on
      microscopic evaluation after death (n=40). Unlike previously used methods, the
      proposed model allows for the preservation of all three aortic valve cusps and a
      more remote placement of the anastomotic suture line from the aortic valve
      annulus. The use of younger recipient rats improves size match and amplifies
      allograft calcification. The purpose of this study was to provide an animal model
      to evaluate modalities of preservation and chemical treatment for aortic valves
      used as allografts or bioprosthesis.

PMID- 9256179
TI  - Should children ever donate kidneys? Views of U.S. transplant centers.
AB  - BACKGROUND: Living donors provide the best outcome for children undergoing renal
      transplantation. Most of these donors are parents. When parents are unable to
      donate, siblings are often considered. But what if the siblings are also
      children? Should they be permitted to donate? METHODS: To see how this difficult
      ethical question is currently handled, a survey was mailed to all U.S. renal
      transplant centers asking for their policies regarding kidney donation by minors
      (< 18 years old). RESULTS: Among the 117 responding centers that offer pediatric
      transplantation, the vast majority (81%) prefer living related donors for
      pediatric recipients. Yet, only 33% of responding centers would allow a
      monozygotic twin minor to donate a kidney to his or her twin, and even fewer
      (21%) would allow a nontwin minor to donate to a sibling. In the year before the
      survey, only two of these centers had actually used a child as a kidney donor.
      Furthermore, the great majority of responding centers (68%) require living donors
      to be at least 18 years old. CONCLUSIONS: These data indicate that most U.S.
      transplant centers are opposed to using children as living kidney donors. On the
      other hand, a careful analysis of this issue suggests that although donation by a
      minor should be uncommon, a complete ban of this practice may be unwarranted. In
      unusual circumstances in which no other suitable donor is available, consenting
      mature minors, and even rare immature minors who are highly likely to benefit
      from donating, may be ethically acceptable. Although there are probably no
      absolute wrong or right answers, the question of kidney donation by children
      should be readdressed.

PMID- 9256180
TI  - Response to diphtheria and tetanus booster vaccination in pediatric renal
      transplant recipients.
AB  - BACKGROUND: Although inactivated vaccines are recommended for immunocompromized
      patients, efficacy and safety of diphtheria and tetanus immunization in renal
      transplant recipients have received little attention so far. The aim of the study
      was to investigate the response to a standard diphtheria and tetanus booster
      vaccination in pediatric renal transplant recipients. METHODS: Forty-two
      children, median age 13.2 years (range, 7.8-18.9 years) with complete primary
      immunization 9.2 years (0.9-15.4 years) before transplantation were enrolled.
      Immunosuppression consisted of cyclosporine plus prednisolone in 15 (36%),
      cyclosporine, azathioprine, and prednisolone in 24 (57%), and tacrolimus plus
      prednisolone in 3 (7%). Antibodies were measured by enzyme-linked immunosorbent
      assay before and 1, 6, and 12 months after vaccination. RESULTS: Before
      vaccination, protective antibody concentrations exceeding 0.1 IU/ml against
      diphtheria were found in 16 children (38%). Thirty-eight (90%) had protective
      antibody concentrations against tetanus. After booster immunization, the
      protection rate against diphtheria rose to 95% at 1 month with a decline to 93%
      at 6 and 76% at 12 months. Protection against tetanus was complete after
      vaccination and persisted over the observation. Antibody concentrations were
      comparable to those reported for healthy children. Statistical analysis showed no
      influence of allograft function, immunosuppressive regimen, previous cytotoxic
      therapy, or time between primary immunization and end-stage renal failure on
      antibody response. Immunization was well tolerated and kidney function remained
      unaffected in patients with stable allograft function. CONCLUSIONS: Diphtheria
      and tetanus vaccination can be performed effectively and safely in renal
      transplant recipients as generally recommended.

PMID- 9256181
TI  - Factors affecting survival after orthotopic liver transplantation in infants.
AB  - The technical and medical management of small infants requiring orthotopic liver
      transplantation remains a challenge. The present study examined 117 orthotopic
      liver transplantations performed in 101 infants from <1 to 23 months of age
      between March 1988 and February 1995 to determine factors that influence patient
      and graft outcome. Factors analyzed included etiology of liver disease, recipient
      and donor age and weight, United Network for Organ Sharing (UNOS) status,
      retransplantation, ABO-compatibility, full-size (FS) versus reduced-size grafts,
      vascular thrombosis (VT), including hepatic artery and portal vein (PVT), and the
      presence of lymphoproliferative disease (LPD). UNOS status 1, fulminant hepatic
      failure, and the development of Epstein-Barr virus-associated LPD were each
      associated with 10-20% lower patient and graft survival rates. Of 101 infants, 11
      (11%) developed LPD with an associated 36% mortality. VT occurred in 10 (9
      hepatic artery and 1 portal vein) of 117 orthotopic liver transplantations (9%),
      all less than 1 year of age, and was associated with significantly poorer 1-year
      (50% vs. 85% no VT, P<0.01) and 5-year patient survival rates (50% vs. 83% no VT,
      P<0.01). One-year graft survival rates for FS grafts in recipients <12 months
      versus 12-23 months were 67% vs. 94% (P<0.01); the patient survival rate was also
      significantly lower in FS graft recipients <12 months (76% vs. 100%, P<0.05).
      Recipients <5 months of age had the worst survival rates: 1-year and 5-year
      patient survival rates were 65% and 46% for recipients 0-4 months (n=17) versus
      82% and 82% for recipients 5-11 months (n=56), and 93% and 93% for recipients age
      12-23 months (n=28; P<0.05). In summary, factors associated with reduced survival
      rates include recipient age <5 months, recipient age <12 months who received FS
      grafts, development of VT and donor weight <6 kg. There was a trend for UNOS
      status 1, fulminant hepatic failure, and presence of LPD to be associated with
      reduced survival rates.

PMID- 9256182
TI  - Use of livers with microvesicular fat safely expands the donor pool.
AB  - BACKGROUND: The safety of transplanting livers with moderate to severe
      microvesicular steatosis is unknown. Livers that appear fatty are often abandoned
      at the donor hospital. We have recently used frozen-section biopsy to distinguish
      between microvesicular and macrovesicular steatosis. We present here our single
      center experience with transplantation of 40 allografts with moderate or severe
      microvesicular steatosis. METHODS: We reviewed our data on 426 transplants and
      identified 40 cases in which the donor liver contained at least 30%
      microvesicular steatosis. Early graft function, patient and graft survival, and
      donor risk factors for steatosis were examined, and results in this cohort were
      compared with results in all other patients who received liver transplants at our
      center during the same time period. We also analyzed the reliability of donor
      frozen-section biopsies in quantitating microsteatosis. Persistence of steatosis
      was assessed on the basis of 1-year follow-up biopsies. RESULTS: The incidence of
      primary nonfunction and poor early graft function was 5% and 10%, respectively.
      One-year patient and graft survival rates were 80% and 72.5%, respectively. Donor
      obesity and traumatic death were commonly identified risk factors for
      microvesicular steatosis. Frozen-section biopsy was reliable for pretransplant
      decision-making about the use of potential grafts, and the steatosis had
      disappeared from the graft at 1 year in the majority of cases. CONCLUSIONS:
      Livers with even severe microvesicular steatosis can be reliably used for
      transplantation without the fear of high rates of primary nonfunction. There was
      a significant incidence of poor early graft function, but this did not affect
      outcome. Microsteatosis is usually associated with some underlying risk factor in
      the donor and is reversible, as demonstrated by follow-up biopsies after
      transplant.

PMID- 9256183
TI  - Central venulitis in the allograft liver: a clinicopathologic study.
AB  - BACKGROUND: Central venulitis denotes a histologic lesion of the allograft liver
      characterized by perivenular and subendothelial mononuclear inflammation of the
      terminal hepatic venules associated with varying degrees of perivenular
      hepatocyte dropout. Although this lesion has generally been considered a
      manifestation of acute rejection, some have suggested that it instead represents
      tacrolimus hepatotoxicity. METHODS: We therefore compared the clinicopathologic
      features of 30 episodes of isolated central venulitis with 22 episodes of
      combined central venulitis and typical portal acute rejection occurring in 27
      patients. Nineteen of the patients received tacrolimus and eight received
      cyclosporine as primary immunosuppression. RESULTS: No significant differences
      were found between the two groups, except that isolated central venulitis more
      often displayed a mild inflammatory component (P=0.007) with small lymphocytes as
      the predominant cell type (P=0.002). None of the patients had tacrolimus or
      cyclosporine levels that exceeded the therapeutic range, and none had other
      clinical evidence of drug toxicity. Usual antirejection therapy was instituted in
      all but two episodes; response was evident in 93% (28 of 30) of the isolated
      central venulitis and 86% (19 of 22) of the central venulitis-portal acute
      rejection group, with histologic regression documented in all follow-up specimens
      (four and five, respectively). Due to persistent central venulitis, two
      cyclosporine patients were switched to tacrolimus, with prompt resolution.
      CONCLUSIONS: These findings are inconsistent with the concept that central
      venulitis represents drug toxicity and indicate instead that it is a form of
      acute allograft rejection.

PMID- 9256184
TI  - Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic
      liver transplantation: a report of the U.S. Multicenter Liver Study Group.
AB  - BACKGROUND: A study was performed by 17 different U.S. liver transplantation
      centers to determine the safety and efficacy of conversion from cyclosporine to
      tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were
      converted to tacrolimus a mean of 319 days after liver transplantation. The
      indication for conversion was ongoing chronic rejection confirmed by biochemical
      and histologic criteria. Patients were followed for a mean of 251 days until the
      end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their
      initial hepatic allograft at the conclusion of the study period and were defined
      as the responder group. Twenty-seven patients (29.7%) failed to respond to
      treatment, and 20 of them required a second liver graft. The actuarial graft
      survival for the total patient group was 69.9% and 48.5% at 1 and 2 years,
      respectively. The actuarial patient survival at 1 and 2 years was 84.4% and
      81.2%, respectively. Two significant positive prognostic factors were identified.
      Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had
      a significantly better graft and patient survival than patients converted with a
      total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time
      between liver transplantation and conversion also affected graft and patient
      survival. Patients converted to tacrolimus < or = 90 days after transplantation
      had a 1-year actuarial graft and patient survival of 51.9% and 65.9%,
      respectively, compared with 73.2% and 87.7% for those converted > 90 days after
      transplantation. The mean total bilirubin level for the responder group was 7.1
      mg/dl at the time of conversion and decreased significantly to a mean of 3.4
      mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during
      the study. Sepsis was the major contributing cause of death in most of these
      patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for
      chronic rejection after orthotopic liver transplantation represents an effective
      therapeutic option. Conversion to tacrolimus before development of elevated total
      bilirubin levels showed a significant impact on long-term outcome.

PMID- 9256185
TI  - Interleukin 6 and interferon-gamma gene expression in lung transplant recipients
      with refractory acute cellular rejection: implications for monitoring and
      inhibition by treatment with aerosolized cyclosporine.
AB  - BACKGROUND: The purpose of this study was to correlate cytokine gene expression
      from bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL)
      with graft histology in recipients with persistent acute rejection treated with
      aerosolized cyclosporine (ACsA). METHODS: We measured mRNA for interleukin (IL)
      6, interferon (IFN)-gamma, and IL-10 in recipients (1) without rejection (n=13),
      (2) with acute rejection that responded to pulsed methylprednisolone (n=7), and
      (3) with "refractory" acute rejection that failed to respond to conventional
      immunosuppression (n=17). In the latter group, ACsA was initiated. RESULTS: BAL
      cell IL-6 and IFN-gamma were highest in recipients with refractory rejection
      compared with recipients with steroid-responsive rejection and recipients with no
      rejection. Improvement in rejection histology occurred in 15 of 17 recipients who
      were treated with ACsA. IL-6 and IFN-gamma mRNA levels from BAL cells decreased
      during treatment with ACsA (median IL-6:actin ratio: before treatment, 0.40 vs.
      after treatment, 0.003, P=0.001; IFN-gamma:actin ratio: before treatment, 0.32
      vs. after treatment, 0.04, P=0.001). PBL IL-6 and IFN-gamma mRNA expression also
      decreased during ACsA treatment after 180 days. Expression of IL-10 mRNA from BAL
      and PBL did not change during ACsA treatment (0.0 vs. 0.03 and 0.0 vs. 0.02,
      respectively). CONCLUSIONS: IL-6 and IFN-gamma mRNA expression from BAL cells was
      highest in those recipients with refractory histologic acute rejection. ACsA was
      associated with decreased IFN-gamma and IL-6 gene expression in BAL cells and
      PBL.

PMID- 9256186
TI  - Immunohistochemical localization of nitric oxide synthase and the oxidant
      peroxynitrite in lung transplant recipients with obliterative bronchiolitis.
AB  - BACKGROUND: Obliterative bronchiolitis (OB) is a disease affecting a large
      percentage of lung and heart-lung transplant recipients. Histologically, the
      disease is characterized by inflammation, cellular proliferation, and
      obliteration of terminal airways. METHODS: We investigated the production of
      inducible and constitutive nitric oxide synthases and peroxynitrite by
      immunohistochemistry in the lungs of control subjects (n=14) compared with those
      of transplant recipients with OB (n=8). RESULTS: Strong immunoreactivity for
      inducible nitric oxide synthase and nitrotyrosine, a marker of protein nitration
      by peroxynitrite, was seen in inflammatory cells, airway epithelium, and vascular
      endothelium of patients with OB, compared with little immunoreactivity in control
      lungs. Immunoreactivity for constitutive nitric oxide synthase was abundant in
      the airway epithelium and vascular endothelium of control lungs, however, it was
      decreased in airway epithelial cells and arterial endothelial cells of patients
      with OB. CONCLUSIONS: We conclude that increased formation of the potent oxidant
      peroxynitrite and decreased production of endothelial nitric oxide may contribute
      to the functional and morphological abnormalities of OB.

PMID- 9256187
TI  - Treatment of renal allograft rejection with T10B9.1A31 or OKT3: final analysis of
      a phase II clinical trial.
AB  - BACKGROUND: Treatment of acute renal allograft rejection with the monoclonal
      antibody (mAb) OKT3 has been shown to be superior to treatment with polyclonal
      antisera. To date, only OKT3 has demonstrated consistent efficacy in reversing
      rejection crisis. METHODS: From 1989 to 1993, a phase II trial comparing the mAb
      T10B9.1A31 (T10B9) with OKT3 for treatment of acute cellular rejection in renal
      allograft recipients was done at the University of Kentucky. We collected data
      from 178 patients potentially eligible to enter the study; 48 never rejected, 9
      refused, 13 could not be biopsied, 16 received methylprednisolone, and 11
      received antithymocyte globulin or OKT3. Altogether, 81 patients entered the
      study, 76 of whom were able to be evaluated. Patients with biopsy-confirmed acute
      rejection were randomly assigned to T10B9 or OKT3 for at least 10 days. RESULTS:
      Demographically, there was no difference between the T10B9 or OKT3 cohorts.
      Actuarial graft survival at 4 years was 87% for patients receiving T10B9, 79% for
      those receiving OKT3, and 89% for those receiving both mAbs (P=0.55). Patient
      survival at 4 years was 94% for T10B9, 100% for OKT3, and 89% for both mAbs
      (P=0.45). Mean creatinines of the cohorts were no different at 1, 6, 12, 24, and
      36 months. There was less cytokine nephropathy (P<0.001) observed in patients
      receiving T10B9. Untoward gastrointestinal, neurological, respiratory, and
      febrile effects were significantly more frequent in the OKT3 cohort after the
      first dose (day 0) and with later (day 1-9) administration. Cytokine levels
      (tumor necrosis factor alpha and interferon gamma) measured 2 hr after the first
      dose were three to six times higher in patients treated with OKT3 than in those
      treated with T10B9 (P<0.005). Infectious complications were not significantly
      different, although serious infections occurred only in patients receiving OKT3.
      No cases of posttransplant lymphoproliferative disorder were seen in either
      cohort. Human anti-mouse antibody development was as follows: titer 1:100, 30%
      T10B9, 42% OKT3; titer 1:1000, 3% T10B9, 3% OKT3. There was no cross-reactivity
      with OKT3 in patients treated with T10B9, and there was only 9.7% cross
      reactivity to T10B9 in patients treated with OKT3. CONCLUSIONS: T10B9 provides
      treatment for renal allograft acute cellular rejection as effective as that of
      OKT3 with fewer untoward effects, less cytokine release and nephropathy, fewer
      serious infections, and without increased development of human anti-mouse
      antibody. The lack of cross-reactivity offers an alternative therapy should the
      first mAb fail or re-rejection occur. A phase III trial should be initiated in
      renal allograft recipients, and phase I and phase II trials should be initiated
      in other solid-organ transplantations.

PMID- 9256188
TI  - Association of hepatitis C virus infection with mortality and graft survival in
      kidney-pancreas transplant recipients.
AB  - BACKGROUND: Although most studies have not demonstrated decreased patient or
      graft survival in kidney-alone allograft recipients infected with hepatitis C
      virus (HCV), the impact of HCV infection on patient and graft survival in HCV
      infected kidney-pancreas recipients has not been studied. METHODS: We undertook a
      retrospective cohort analysis of 137 kidney-pancreas transplant recipients who
      were transplanted between January 1989 and May 1996. HCV infection was determined
      by a positive polymerase chain reaction. Relative risk of death and graft failure
      was calculated using the Cox proportional hazards model with time-dependent
      covariates. Relative risks were adjusted (aRR) to control for the number of OKT3
      treated rejections and cytomegalovirus status of the recipient at the time of
      transplantation. RESULTS: Mean length of follow-up was 30.4 months in the HCV
      infected patients compared with 31.7 months in noninfected patients. Seven (5.1%)
      patients were infected with HCV before transplant, one (1%) relapsed after
      transplantation, and four (2.9%) acquired the infection after transplantation.
      The HCV-infected group had a 3.7-fold (95% confidence interval [CI], 1.0-13.5)
      increased risk of death after transplant compared with the HCV-negative group,
      with an aRR of 5.5 (95% CI, 1.5-20.0). Death in the HCV-infected group (n=3) was
      generally the result of liver failure and sepsis, whereas death for those in the
      uninfected group (n=11) was primarily of cardiovascular origin. Patients infected
      with HCV were 3.4-fold (95% CI, 1.1-10.1) more likely to develop kidney graft
      failure than HCV-negative patients with an aRR of 5.1 (95% CI, 1.7-15.4). The
      risk of pancreatic allograft failure was not significantly increased.
      CONCLUSIONS: We conclude that HCV infection in kidney-pancreas transplant
      patients results in a significantly increased risk of kidney allograft failure
      and death.

PMID- 9256189
TI  - Analysis of hospital charges after simultaneous pancreas-kidney transplantation
      in the era of managed care.
AB  - BACKGROUND: The purpose of this study was to analyze and compare hospital charges
      in simultaneous pancreas-kidney transplant (SPKT) recipients before and after
      implementation of managed care principles. METHODS: Two groups were compared: 14
      consecutive SPKT patients transplanted in 1991 vs. 15 consecutive SPKT patients
      transplanted in 1995. All patients underwent whole organ pancreas transplantation
      with bladder drainage and received quadruple immunosuppression with OKT3
      induction. The two groups were well-matched; outliers were excluded (four in 1991
      and five in 1995), and no attempt was made to convert 1991 to 1995 dollars.
      Patient and graft survival rates were 100%, and no major early complications
      occurred. All SPKTs were performed in a single hospital setting, and all
      inpatient charges for the initial hospitalization were analyzed retrospectively
      and itemized by service. RESULTS: Pharmacy, organ acquisition, and clinical
      laboratory services accounted for nearly 80% of charges in each group. For the
      initial transplant hospitalization, the 1995 group experienced significant
      reductions in: (1) length of stay (16.3+/-1.4-135+/-3.5 days, P=0.03); (2) total
      number of laboratory tests (392+/-15-224+/-60, P<10(-3)); (3) clinical laboratory
      charges ($23,623+/-$1,780-$11,165+/-$3,091, P<10(-6)); and (4) total inpatient
      charges with organ acquisition charges excluded ($87,815+/-$8,678-$75,152+/
      $16,871, P=0.049). However, these potential savings were offset by a nearly 47%
      increase in organ acquisition charges and a 38% increase in medical/surgical
      supplies. Consequently, total hospital charges for SPKT were no different in 1991
      and 1995. CONCLUSIONS: Despite the rising costs of medical care, we have
      implemented managed care principles after SPKT that were successful in
      stabilizing hospital charges by decreasing length of stay and clinical laboratory
      tests during the study period. However, escalating charges related to organ
      acquisition and medical/surgical supplies remain a problem.

PMID- 9256190
TI  - Induction of T helper 2 immunity to an immunodominant allopeptide.
AB  - Neonatal tolerance to alloantigens and autoantigens in mice is mediated by T
      helper (Th)2 immunity. If a strong and pure Th2 response could be engaged to
      alloantigens in adult mice, it might result in allograft tolerance. In an attempt
      to induce Th2 immunity in adults, we studied the T-cell response to peptide I-A
      beta(k)58-71 (I-Ap), a dominant indirect pathway determinant during rejection of
      B10.A skin by BALB/c mice. Our data show that the naturally occurring response to
      this peptide during rejection is Th1, consistent with the notion that Th1
      immunity is central to destruction of the allograft. In contrast, vigorous and
      unipolar Th2-type immunity to this peptide can be readily induced by
      intraperitoneal immunization with incomplete Freund's adjuvant, a protocol
      previously thought to induce T-cell unresponsiveness. Thus, adjuvant can be used
      to Th2-guide the indirect pathway alloresponse in an effort to antagonize
      naturally occurring Th1 alloimmunity.

PMID- 9256191
TI  - Delaying transplantation after total body irradiation is a simple and effective
      way to reduce acute graft-versus-host disease mortality after major H2
      incompatible transplantation.
AB  - BACKGROUND: We have previously reported that delaying histoincompatible
      transplantation after total body irradiation (TBI) conditioning markedly
      decreased the mortality of acute graft-versus-host disease (GVHD) in severe
      combined immunodeficiency mice. However, it was not clear whether the delayed
      transplantation would affect the final engraftment and acute GVHD mortality in
      normal hosts. METHODS: BALB/c mice (H2d) were lethally irradiated with 8.5 Gy TBI
      and transplanted with C57BL/6 (H2d) bone marrow plus spleen cells on the same day
      (TBI+day 0) or 4 days after TBI conditioning (TBI+day 4). RESULTS: We again
      demonstrated that delaying transplantation by 4 days after TBI conditioning
      markedly reduced acute GVHD mortality in normal hosts after major
      histoincompatible transplantation. The survival rates were 66% in TBI+day 4 vs.
      0% in TBI+day 0 allogeneic transplanted animals by day +60 (P<0.001). Further
      analysis demonstrated that the 4-day rest between the TBI and allogeneic
      transplantation broke the interaction of cell/inflammatory tumor necrosis factor
      alpha, interleukin (IL)-1beta, and IL-6 cytokine reactions stimulated by TBI and
      incompatible transplantation. Flow cytometry revealed 97% donor cells in host
      marrow by 2 weeks in TBI+day 0 transplantation versus 57% in TBI+day 4
      transplantation. There was no difference in percentage of donor CD3+ T-cell
      engraftment between the TBI+day 0 and TBI+day 4 allogeneic transplanted animals.
      In TBI+day 4 transplantation, the percentage of donor cells in host marrow
      steadily increased to 74% by day +60 and 93% by day +100. CONCLUSIONS: This 2- to
      3-month early mixed chimerism in TBI+day 4 transplanted animals might be related
      to lower levels of tumor necrosis factor-alpha and IL-6 both of which have been
      shown to stimulate lymphohematopoiesis and was associated with lower acute GVHD
      mortality. The data again demonstrated in immunologically normal BALB/c mice that
      delaying allogeneic transplantation after TBI is a simple and effective way to
      reduce acute GVHD mortality, achieve satisfactory engraftment and significantly
      increase overall survival.

PMID- 9256192
TI  - Phenotype and localization of macrophages expressing inducible nitric oxide
      synthase in rat hepatic allograft rejection.
AB  - BACKGROUND: We investigated the phenotype and localization of macrophages
      expressing inducible nitric oxide synthase (iNOS) in rat hepatic allografts,
      using double immunostaining with anti-macrophage iNOS (macNOS) and rat anti
      macrophage (ED1 or ED2) monoclonal antibodies. METHODS: The animals were divided
      into three experimental groups: group 1, isografts; group 2, untreated hepatic
      allografts; and group 3, hepatic allografts treated with FK506. RESULTS: Plasma
      nitrite/nitrate concentrations in group 2 increased on day 3, peaked on day 5,
      and decreased thereafter. In contrast, the plasma nitrite/nitrate concentrations
      in group 1 increased slightly on day 3, but decreased gradually thereafter. The
      plasma concentrations of nitrite/nitrate did not vary in group 3. The peak
      nitrite/nitrate values in group 2 were significantly greater than those in groups
      1 and 3. The number of macNOS+ cells peaked on day 5 in group 2. In contrast, a
      few macNOS+ cells were seen in the liver grafts of groups 1 and 3. Double
      immunostaining revealed that the macNOS+ cells consisted of macNOS+ ED1+ (80%)
      and macNOS+ ED2+ (40%) in the untreated hepatic allografts on day 5. In addition,
      a number of macNOS+ cells also were seen in the red pulp of the recipient spleen
      in the untreated hepatic allografts. CONCLUSIONS: These results suggest that the
      intense iNOS expression by the monocyte/macrophage lineage among the hepatic
      infiltrates and by the splenic macrophages after transplantation supports a role
      for nitric oxide in the immunomodulation of allogeneic responses in local and
      remote organs, and possibly serves as a mediator of cytotoxic graft damage.

PMID- 9256193
TI  - Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat
      model of bronchiolitis obliterans.
AB  - BACKGROUND: Bronchiolitis obliterans is the most significant complication
      adversely affecting prolonged survival of lung allograft recipients. The
      evolution from the initial insult to the final pathologic entity is largely
      unknown. The aim of this study was to characterize the evolution of transplant
      induced fibrous airway obliteration in a rat tracheal transplant model of
      bronchiolitis obliterans. METHODS: Tracheal segments were transplanted from Brown
      Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts).
      Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap.
      They were harvested at 14 different time points (from 1 day to 1 year after
      transplantation) and assessed histologically. RESULTS: The fibrous airway
      obliteration developed only in allografts showing a triphasic time course: an
      initial ischemic phase (observed in both isografts and allografts) was followed
      by a marked lymphocytic infiltrative phase with complete epithelial loss
      (observed only in allografts, P<0.01), and finally by an obliterative phase with
      fibrous obliteration of the allograft airway lumen (P<0.01). CONCLUSIONS: This
      animal model shows a distinct and reproducible triphasic time course in the
      development of obliterative airway lesions in allografts. It confirms that the
      mechanism leading to airway obliteration is immune mediated as only allografts
      showed this lesion and that lymphocytic infiltration is a precursor of the lesion
      in this model. The insights into the different phases demonstrated may lead to
      novel approaches regarding the type and timing of therapeutic interventions.

PMID- 9256195
TI  - Morphometric analysis of neointimal formation in murine cardiac allografts: II.
      Rate and location of lesion development.
AB  - BACKGROUND: Transplant vascular sclerosis (TVS) is manifested in transplanted
      human and murine hearts as a concentric, intimal lesion. The purpose of this
      study was to characterize the rate, location, and intensity of developing TVS
      lesions in murine cardiac allografts using quantitative morphometric analysis.
      METHODS: Murine cardiac allografts, treated with the immunosuppressant gallium
      nitrate, were explanted at 30, 60, and 90 days after transplant. The grafts were
      histologically stained and evaluated for intimal thickening by deriving a
      neointimal index (NI) using a computerized image-analysis system. RESULTS: In
      cardiac allografts, mild vascular lesions of varying NI were detectable by day 30
      and lesion severity increased significantly by day 60. Thereafter, average lesion
      severity stabilized, although the percentage of affected vessels continued to
      increase from day 30 to day 90. In contrast, day-90 cardiac isografts showed
      little to no TVS development. Vascular lesions developed randomly without regard
      for vessel location or size. TVS developed more regularly in vessels of the
      interventricular septum than in the right or left ventricular walls. The degree
      of TVS development fluctuated along the length of individual vessels, even as
      late as 90 days after transplant. The smaller vessels (<85 microm in diameter)
      appeared to occlude more quickly than the larger vessels. CONCLUSIONS: TVS
      developed reproducibly in a random pattern throughout cardiac allografts over a 1
      month to 3-month period after transplant. This development can be quantitatively
      monitored by computerized morphometric analysis. In general, under these
      experimental conditions, 30-day cardiac allografts seem to provide a useful
      experimental model for studying early aspects of TVS, whereas 60-day allografts
      may be better suited for analysis of advanced TVS.

PMID- 9256194
TI  - Effect of anti-CD4 monoclonal antibody combined with human CTLA4Ig on the
      survival of hamster liver and heart xenografts in Lewis rats.
AB  - We investigated the effects of pretransplant anti-CD4 monoclonal antibody (mAb)
      combined with human (h) CTLA4Ig on the survival of hamster heart and liver
      xenografts. Pretransplant anti-CD4 mAb (5 mg/kg x 4 days) or hCTLA4Ig (0.5 mg/rat
      on days 1, 3, and 5 after transplantation) treatment alone prolonged the survival
      of hamster liver xenografts in Lewis rats (mean survival time [MST]=10.5 days,
      n=6, and MST=9.0 days, n=5, respectively, compared with untreated Lewis
      recipients of hamster liver grafts, MST=6.0 days, n=6). The same regimen could
      not prevent hamster heart xenorejection. Pretransplant anti-CD4 mAb (5 mg/kg x 4
      days) combined with hCTLA4Ig (0.5 mg/rat x 4) treatments increased survival of
      hamster liver xenograft fourfold (MST=24.2 days, n=5). The current results also
      show that IgG in the sera from Lewis recipients of hamster liver grafts treated
      with anti-CD4 mAb and hCTLA4Ig was threefold reduced at 6 days after
      transplantation compared with untreated Lewis rats. These results suggest a
      synergistic effect of anti-CD4 mAb combined with hCTLA4Ig in a liver xenograft
      transplantation model.

PMID- 9256196
TI  - Prolonged survival of mouse skin allografts in recipients treated with donor
      splenocytes and antibody to CD40 ligand.
AB  - Combined treatment with antibody against CD40 ligand and one transfusion of donor
      splenocytes prolonged survival of fully mismatched BALB/c skin allografts on
      C57BL/6 recipients, with approximately 20% of grafts surviving > 100 days. In
      vitro alloresponsiveness in treated animals was reduced in the immediate post
      transplantation period, but by day 100 was increased despite the presence of a
      successful allograft. The presence of alloreactivity on day 100 was confirmed in
      vivo by adoptive transfer, which suggests that our protocol had induced either a
      state of "split tolerance" or "graft accommodation." Mice with skin grafts that
      had survived for > or = 100 days revealed no evidence of lymphoid chimerism.
      Treatment with donor splenocytes and antibody against CD40 ligand permits long
      term survival of highly antigenic donor skin allografts despite the presence of
      functionally intact alloreactive lymphocytes.

PMID- 9256197
TI  - CD4+ T cells are able to reject class I disparate allografts.
AB  - The ability of CD4+ T cells to reject class I mismatched skin allografts remains
      controversial. In this study, we compare the ability of CD4+ T cells to reject
      class I disparate skin grafts differing by either a single class I allelic
      disparity or only 3 amino acids encoded by the H-2K locus. We demonstrate that
      skin grafts across a full H-2K allelic disparity, but not across a disparity of
      only three amino acids are efficiently rejected by CD4+ T cells. This observation
      is consistent with the possibility that peptides derived from allogeneic class I
      molecules generated through the major histocompatibility complex (MHC) class II
      antigen processing pathway can be recognized by host CD4 T cells and lead to
      rejection of class I mismatched skin grafts. The availability of peptides derived
      from allogeneic MHC class I molecules for presentation by host MHC class II may
      determine the efficiency of rejection of class I mismatched allografts by CD4+ T
      cells. Thus, class I mismatched allografts can be rejected by CD4+ T cells
      provided that host and donor MHC class I molecules are sufficiently disparate to
      activate CD4+ effectors.

PMID- 9256198
TI  - Recognition of porcine major histocompatibility complex class I antigens by human
      CD8+ cytolytic T cell clones.
AB  - To evaluate the nature of the human cellular immune response to porcine
      xenoantigens, cytolytic T lymphocyte (CTL) cell lines were generated against
      porcine aortic endothelial cells (PAEC). After four stimulations, the phenotypes
      of the T cell lines were primarily CD8+ (79.7+/-19.6%). Natural killer cells were
      not detected. Functional analysis of the T cell lines showed specific
      cytotoxicity against syngeneic porcine targets with no lysis of unrelated porcine
      cells, human cells, or K562, a natural killer target. The major
      histocompatibility complex (MHC) specificity of this response was confirmed when
      T cell lines established against PAEC from partially inbred SLAdd miniature swine
      lysed only PAEC and phytohemagglutinin-stimulated lymphocytes from SLAdd origin
      but not SLAgg targets. Both CD8+ (7/12) and CD4+ (5/12) T cell clones were
      generated from the bulk cell lines. All of the CD8+ T cell clones specifically
      lysed stimulator PAEC and swine leukocyte antigen (SLA)-matched,
      phytohemagglutinin-stimulated lymphocyte targets but not unrelated porcine
      targets. CD4+ T cell clones, as expected, showed no lysis of any porcine target
      cells. The lysis of porcine targets by the human CD8+ cytotoxic T lymphocyte
      clones was inhibited by monoclonal antibodies against SLA class I antigens and
      human CD8, which indicates that human CD8+ T cells recognize porcine MHC class I
      molecules. These results, which show that human T cells differentiate between
      porcine MHC alleles, have relevance in the clinical application of xenografts.

PMID- 9256199
TI  - A molecular epidemiological probe for pig microchimerism.
AB  - We have cloned and characterized a single-copy DNA sequence from the porcine
      alpha-1,3-galactosyltransferase gene that corresponds to a 547-base pair intron
      separating exons 3 and 4 of the protein coding domain. Polymerase chain reaction
      amplification of this sequence from flanking oligonucleotides generates a species
      specific DNA probe (pgt34) capable of recognizing 50 pg chimeric template DNA at
      a pig to human cellular ratio of 1/10,000. Homologous DNA sequence is not
      identified in the macaque, baboon, or human genome by Southern hybridization.
      Analysis of a discordant model of pig to baboon xenotransplantation demonstrates
      peripheral blood microchimerism in the presence of a functioning pig kidney
      xenograft and persistence of microchimerism in lymphatic tissue after graft
      removal. This probe should be useful for tracking the fate of porcine cells in
      patients undergoing xenotransplantation of whole organs or free tissues such as
      pancreatic islet cells and should facilitate studies of microchimerism in
      experimental models of pig to monkey xenotransplantation.

PMID- 9256201
TI  - Early detection of graft function using hepatic venous oxygen saturation in pig
      liver transplantation.
AB  - In this study, we measured hepatic venous oxygen saturation (Shvo2) in pig liver
      transplantations in order to evaluate its usefulness as a predictor of early
      postoperative graft function. Shov2 of the grafts with good function was over 60%
      after reperfusion, and the mean Shov2 at end of the operations was 69.8+/-6.9%.
      Shov2 of the grafts with poor function never increased over 60%, and for most of
      the operation until its end, Shov2 was under 50%. At the end of the operations,
      the mean Shov2 was 39.7+/-5.5%. Shov2 levels of the grafts with good function
      were significantly higher than those of the grafts with poor function (P=0.0016).
      Corresponding with these Shov2 data, glutamic-oxaloacetic transaminase and
      lactate dehydrogenase levels of grafts with poor function were significantly
      higher than those of the grafts with good function. Shov2 represents a summation
      of the hemoglobin oxygen saturation at the venous end of the sinusoids of the
      liver and indicates adequate hepatic blood flow if the hepatic oxygen is
      constant. A decrease of Shov2 in poor graft function might indicate a disturbance
      of microcirculation in the sinusoids. Through the use of Shov2, we are able to
      recognize conditions of microcirculatory disturbance more quickly than with any
      other system. In conclusion, Shov2 is a useful indicator for an early and
      reliable prediction of outcome in liver transplantation.

PMID- 9256200
TI  - Alloreactive cytotoxic T lymphocytes focus on specific major histocompatibility
      complex-bound peptides.
AB  - Alloreactive T cells are often specific for individual peptides that are bound to
      allogeneic major histocompatibility complex (MHC) molecules. Other alloreactive T
      cells are reported to be peptide-independent or to recognize MHC conformational
      changes that are induced by multiple peptides. We tested 12 anti-HLA-B7
      alloreactive cytotoxic T lymphocyte (CTL) clones that bind a restricted region of
      HLA-B7, including three CTL clones that were generated in a protocol designed to
      stimulate peptide-independent T cells. All 12 CTLs recognized multiple point
      mutations in the HLA-B7 peptide-binding groove. Eleven of the 12 CTLs recognized
      specific peptides that eluted in one or two fractions on high-performance liquid
      chromatography (HPLC). None of the CTLs promiscuously recognized 16 HLA-B7
      binding synthetic peptides, although one CTL recognized minor by-products in one
      synthetic peptide preparation. CTL clone KID-9 cross-reacted with allogeneic HLA
      B7 and HLA-B27 molecules and recognized a distinct peptide bound to each MHC
      molecule. CTL clone KD-11 recognized peptides that eluted in two HPLC fractions
      and recognized HLA-B7-transfected peptide antigen processing defective T2 cells.
      These results indicate that CTL allorecognition is peptide-specific whether the
      allogeneic MHC molecules are expressed on normal cells or antigen processing
      deficient cells.

PMID- 9256203
TI  - Successful transplantation of organs retrieved from donors with bacterial
      meningitis.
AB  - BACKGROUND: The shortage of organs for transplantation is the most important
      factor limiting the number of transplants performed. Consequently, in recent
      years, criteria for considering a patient as a potential organ donor have been
      broadened. METHODS: From 1995 through 1996, we have retrieved organs from five
      donors who were brain dead because of bacterial meningitis. The causative
      microorganisms were Neisseria meningitidis in one patient, Streptococcus
      pneumoniae in three patients, and Escherichia coli in one patient. Fifteen organs
      were retrieved and transplanted into 16 recipients. All the donors and recipients
      received adequate antibiotic therapy. RESULTS: None of the recipients developed
      infectious complications caused by the meningeal pathogens. After a follow-up
      ranging from 4 to 30 months, 12 patients are alive with functioning grafts. The
      cause of death was noninfectious in the four patients who died. CONCLUSIONS: Our
      study demonstrates that patients with brain death caused by bacterial meningitis
      due to meningococci, pneumococci, or E coli may be suitable organ donors.
      Transplantation of organs from such donors does not increase the risk of
      infection transmission to the recipient, provided that both donor and recipient
      had received adequate antibiotic therapy.

PMID- 9256202
TI  - Donor peripheral blood stem cell infusions in recipients of living-related liver
      allografts.
AB  - BACKGROUND: In this pilot study, donor peripheral blood stem cell (DPBSC)
      infusions were performed in three recipients of living-related liver transplants
      (LRLT). METHODS: DPBSCs were obtained by leukapheresis after mobilization with
      granulocyte-colony-stimulating factor (Filgrastim). Donor leukapheresis was
      performed on the 5th postoperative day, and half of the DPBSCs were infused into
      the recipient on the day of collection. The second half of the pheresed product
      was cryopreserved for delayed administration. RESULTS: Results from preliminary
      studies of chimerism in LRLT recipients, at 20 weeks posttransplant, suggested
      that the levels of donor cells detected in LRLT recipients treated with DPBSC
      infusions may be higher than those observed for recipients of cadaver donor liver
      allografts and vertebral body marrow infusions. CONCLUSIONS: The results of this
      pilot study indicate that administration of mobilized DPBSC to recipients of LRLT
      is a feasible procedure for both donor and recipient.

PMID- 9256204
TI  - Are surveillance endomyocardial biopsies necessary during OKT3 induction therapy?
AB  - BACKGROUND: To determine the utility of surveillance endomyocardial biopsies
      (EMBs) during a 14-day OKT3 induction course after cardiac transplantation,
      histologic results of the first two EMBs were retrospectively reviewed. METHODS:
      Seventy-three consecutive cardiac transplant recipients who received an OKT3
      based quadruple sequential immunosuppressive protocol were analyzed. Patients
      were predominantly white (85%) and male (72%), with ischemic cardiomyopathy (54%)
      and a pretransplant panel-reactive antibody level of <10% (93%). RESULTS: The
      first EMB in 73 patients demonstrated no rejection in 70 patients (96%) and grade
      1A rejection in 3 patients (4%). The second EMB showed no rejection in 64
      patients (88%), grade 1A or 1B rejection in 8 patients (11%), and grade 3A
      rejection without hemodynamic compromise in only 1 patient (1%). Absolute CD3+
      cells remained below 25 lymphocytes/mm3, and mean trough OKT3 serum levels
      exceeded 500 ng/ml throughout the 14 days of therapy, demonstrating the
      immunosuppressive efficacy of OKT3. Posttransplant echocardiograms showed normal
      left ventricular systolic function. CONCLUSIONS: Since 145 of 146 EMBs (99%)
      demonstrated no or minimal allograft rejection, a large cost savings could be
      realized if EMBs were performed only when clinically indicated during the 14-day
      OKT3 induction course in cardiac transplant recipients. Appropriate immunologic
      monitoring and echocardiographic testing may obviate the need for performing
      costly EMBs during OKT3 induction without an adverse clinical outcome.

PMID- 9256205
TI  - Some aspects of justice in the allocation of organs for transplantation.

PMID- 9256206
TI  - The cardiology beat. An Internet education for patients and health professionals.

PMID- 9256207
TI  - Dartmouth Medical School bicentennial.

PMID- 9256208
TI  - Concern expressed about FDA reform legislation.

PMID- 9256209
TI  - From the Centers for Disease Control and Prevention. Interim guidelines for
      prevention and control of staphylococcal infection associated with reduced
      susceptibility to vancomycin.

PMID- 9256210
TI  - From the Centers for Disease Control and Prevention. Heat-related deaths--Dallas,
      Wichita, and Cooke counties, Texas, and United States, 1996.

PMID- 9256211
TI  - A piece of my mind. Res ipsa loquitur.

PMID- 9256212
TI  - Are "America's Best Hospitals" America's best?

PMID- 9256213
TI  - Are "America's Best Hospitals" America's best?

PMID- 9256214
TI  - Are "America's Best Hospitals" America's best?

PMID- 9256215
TI  - Are "America's Best Hospitals" America's best?

PMID- 9256216
TI  - Facilitating patient-specific decisions regarding hormone replacement therapy.

PMID- 9256217
TI  - Facilitating patient-specific decisions regarding hormone replacement therapy.

PMID- 9256218
TI  - Molecular diagnosis of circulating cancer cells using MAGE gene assays.

PMID- 9256219
TI  - Venous thromboembolic events associated with hormone replacement therapy.

PMID- 9256220
TI  - Reporting institutional review board approval and patient consent.

PMID- 9256221
TI  - Individual vs laboratory variation in blood lipid values: updating the
      literature.

PMID- 9256222
TI  - Long-term protection from myocardial ischemic events in a randomized trial of
      brief integrin beta3 blockade with percutaneous coronary intervention. EPIC
      Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of
      Ischemic Complication.
AB  - CONTEXT: Abciximab, a monoclonal antibody fragment against the platelet receptor
      alphaIIb beta3 integrin, prevents platelet aggregation. A randomized, placebo
      controlled study showed that abciximab improves outcomes for patients undergoing
      percutaneous coronary angioplasty at 30 days and at 6 months. OBJECTIVE: To
      determine whether abciximab improves outcomes 3 years after coronary angioplasty.
      DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING: A total of
      56 academic and community hospitals in the United States. PATIENTS: A total of
      2099 high-risk patients undergoing coronary angioplasty were randomized.
      Sufficient time elapsed for 2.5 years of follow-up among 2001 patients and for 3
      years of follow-up among 1599 patients. INTERVENTIONS: Abciximab bolus of 0.25
      mg/kg followed by infusion at 10 microg/min for 12 hours; abciximab bolus of 0.25
      mg/kg followed by placebo infusion; or placebo bolus followed by placebo
      infusion. MAIN OUTCOMES MEASURES: The primary outcome was the composite of death,
      myocardial infarction, or coronary revascularization. Secondary outcomes were
      death, myocardial infarction, or coronary revascularization individually.
      Subgroups having refractory unstable angina or evolving myocardial infarction and
      having different elevations of creatine kinase during initial angioplasty were
      analyzed. RESULTS: At 3 years, composite end points occurred in 41.1% of those
      receiving abciximab bolus plus infusion; 47.4% of those receiving abciximab bolus
      only; and 47.2% of those receiving placebo only (for abciximab bolus plus
      infusion vs placebo, P=.009). Death occurred in 6.8%, 8.0%, and 8.6%,
      respectively (for abciximab bolus plus infusion vs placebo, P=.20); myocardial
      infarction in 10.7%, 12.2%, and 13.6%, respectively (for abciximab bolus plus
      infusion vs placebo, P=.08); and revascularization in 34.8%, 38.6%, and 40.1%,
      respectively (for abciximab bolus plus infusion vs placebo, P=.02). Among those
      with refractory unstable angina or evolving myocardial infarction, death occurred
      in 5.1%, 9.2%, and 12.7%, respectively (for abciximab bolus plus infusion vs
      placebo, P=.01). Death rates increased as periprocedural creatine kinase levels
      increased. CONCLUSIONS: Abciximab bolus with infusion given at the time of
      coronary angioplasty improves outcomes as long as 3 years after the procedure.

PMID- 9256223
TI  - Severity-adjusted mortality and length of stay in teaching and nonteaching
      hospitals. Results of a regional study.
AB  - CONTEXT: Major teaching hospitals are perceived as being more expensive than
      other hospitals and, thus, unattractive to managed care. However, little
      empirical data exist about their relative quality and efficiency. The current
      study compared severity-adjusted mortality and length of stay (LOS) in teaching
      and nonteaching hospitals. DESIGN: Retrospective cohort study. SETTING: Thirty
      hospitals in northeast Ohio. PATIENTS: A total of 89851 consecutive eligible
      patients discharged in 1991 through 1993 with myocardial infarction, congestive
      heart failure, obstructive airway disease, gastrointestinal hemorrhage,
      pneumonia, or stroke. MAIN OUTCOME MEASURES: In-hospital mortality and LOS of
      patients in major teaching (n=5), minor teaching (n=6), and nonteaching (n=19)
      hospitals were adjusted for admission severity of illness using multivariable
      models based on demographic and clinical data abstracted from patients' medical
      records. RESULTS: The adjusted odds of death was 19% lower (95% confidence
      interval [CI], 2%-34%; P=.03) for patients in major teaching hospitals compared
      with non-teaching hospitals but was similar (95% CI, 7% lower to 28% higher;
      P=.28) for patients in minor teaching hospitals. The findings were generally
      consistent in analyses stratified according to diagnosis, age, race, predicted
      risk of death, and other covariates. In addition, risk-adjusted LOS was 9% lower
      (95% CI, 8%-10%; P<.001) among patients in major teaching hospitals relative to
      nonteaching hospitals but was similar (95% CI, 2% lower to 11% higher; P=.17) in
      minor teaching hospitals. Major teaching hospitals also cared for higher
      proportions of nonwhite and poorly insured patients. CONCLUSIONS: Risk-adjusted
      mortality and LOS were lower for patients in major teaching hospitals than for
      patients in minor teaching and nonteaching hospitals. If generalizable to other
      regions, the results provide evidence that hospital performance, as assessed by 2
      commonly used indicators, may be higher in major teaching hospitals. These
      findings are noteworthy at a time when the viability of many major teaching
      hospitals is threatened by powerful health care market forces and by potential
      changes in federal financing of graduate medical education.

PMID- 9256224
TI  - Prognostic factors in meningococcal disease. Development of a bedside predictive
      model and scoring system. Barcelona Meningococcal Disease Surveillance Group.
AB  - CONTEXT: Meningococcal disease is associated with significant morbidity and
      mortality. Development of a prognostic model based on clinical findings may be
      useful for identification and management of patients with meningococcal
      infection. OBJECTIVES: To construct and validate a bedside model and scoring
      system for prognosis in meningococcal disease. DESIGN: Prospective, population
      based study. SETTING: Twenty-four hospitals in the metropolitan area of
      Barcelona, Spain. PATIENTS: A total of 907 patients with microbiologically proven
      meningococcal disease. Patients diagnosed with meningococcal disease from 1987
      through 1990 were used to develop the prognostic model, and those diagnosed in
      1991 and 1992 were used to validate it. OUTCOME MEASURES: Clinical independent
      prognostic factors for mortality in meningococcal disease. The association
      between outcome and independent prognostic factors was determined by logistic
      regression analysis. A scoring system was constructed and tested using receiver
      operating characteristic curves. RESULTS: Among 624 patients in the derivation
      set, 287 (46%) were male, the mean age was 12.4 years, and 34 patients (5.4%)
      died. Among 283 patients in the validation set, 124 (43.8%) were male, the mean
      age was 12.7 years, and 17 patients (6.0%) died. In multivariate analysis,
      independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 101;
      95% confidence interval [CI], 30-333), focal neurologic signs (OR, 25; 95% CI, 7
      83), and age 60 years or older (OR, 10; 95% CI, 3-34), whereas receipt of
      adequate antibiotic therapy prior to admission was associated with reduced
      likelihood of death (OR, 0.09; 95% CI, 0.02-0.4). Hemorrhagic diathesis was
      scored with 2 points, presence of focal neurologic signs with 1 point, age of 60
      years or older with 1 point, and preadmission antibiotic therapy was scored as 
      1. The clinical scores of -1, 0, 1, 2, and 3 or more points were associated with
      a probability of death of 0%, 2.3%, 27.3%, 73.3%, and 100%, respectively.
      CONCLUSIONS: Hemorrhagic diathesis, focal neurologic signs, and age of 60 years
      or older were independent predictors of death in meningococcal disease, whereas
      receipt of adequate antibiotic therapy was associated with a more favorable
      prognosis. The scoring system presented is simple, is based on findings readily
      available at the bedside, and may be useful to help guide aggressive therapy.

PMID- 9256225
TI  - Adherence to prescribed explicit criteria during utilization review. An analysis
      of communications between attending and reviewing physicians.
AB  - CONTEXT: Utilization review (UR) seeks to improve quality and cost-efficiency of
      health care. However, how well the process works in practice has not been
      assessed. OBJECTIVE: To describe the outcomes of a sample of physician reviews in
      terms of the explicit criteria that the UR was designed to implement. DESIGN:
      Retrospective analysis of transcripts of precertification reviews. PARTICIPANTS
      AND SETTING: California physicians employed by a UR firm conducted 96 interviews
      from April 1990 to July 1991 with attending physicians who had proposed to insert
      tympanostomy tubes on a patient younger than 16 years and whose proposals had
      been found to be inappropriate on an initial screen. MAIN OUTCOME MEASURES: The
      appropriateness rating assigned to each case by the physician-reviewer and by the
      investigators using explicit criteria. Logistic regression identified factors
      associated with the reviewers' recommendations to perform surgery and with
      recommendations at variance from the criteria. RESULTS: The reviewers recommended
      78% of cases for surgery, of which only 29% were supported by the criteria or had
      extenuating circumstances. The criteria concurred with all 30 of the reviewers'
      recommendations against surgery. Two factors, female sex (odds ratio [OR], 8.2;
      95% confidence interval [CI], 1.2-53.8) and previous tympanostomy tube insertion
      (OR, 30.9; 95% CI, 2.4-394.8) were associated with reviewer recommendations in
      favor of surgery that were at variance from the criteria, despite the lack of
      evidence for either as a mitigating circumstance. CONCLUSION: Physician reviewers
      were more lenient than the explicit criteria that the reviews were designed to
      implement. In no cases did the reviewers depart from the criteria's
      recommendations in favor of surgery.

PMID- 9256226
TI  - Calibrating the physician. Personal awareness and effective patient care. Working
      Group on Promoting Physician Personal Awareness, American Academy on Physician
      and Patient.
AB  - Physicians' personal characteristics, their past experiences, values, attitudes,
      and biases can have important effects on communication with patients; being aware
      of these characteristics can enhance communication. Because medical training and
      continuing education programs rarely undertake an organized approach to promoting
      personal awareness, we propose a "curriculum" of 4 core topics for reflection and
      discussion. The topics are physicians' beliefs and attitudes, physicians'
      feelings and emotional responses in patient care, challenging clinical
      situations, and physician self-care. We present examples of organized activities
      that can promote physician personal awareness such as support groups, Balint
      groups, and discussions of meaningful experiences in medicine. Experience with
      these activities suggests that through enhancing personal awareness physicians
      can improve their clinical care and increase satisfaction with work,
      relationships, and themselves.

PMID- 9256228
TI  - Federalism and health system reform. Prospects for state action.
AB  - OBJECTIVE: To assess the prospect that the states, acting independently, would
      undertake health insurance coverage expansions that together would result in
      meaningful reductions in the extent of uninsurance nationally. DESIGN: We use
      microsimulation methods to contrast the federal income tax payments needed to
      finance a national program covering the uninsured with the state income tax
      payments needed to finance a state-specific program for the same purpose. The
      contrast reveals the effects on the tax burdens of differences among states in
      uninsured rates and tax capacity. SETTING: Continental United States. PATIENTS OR
      OTHER PARTICIPANTS: Observations from the 1990 through 1993 Current Population
      Survey (N =305 477 families), weighted to represent the population of each state.
      INTERVENTION: Illustrative public health insurance program for families with
      incomes below 250% of poverty, not covered by current public or employer
      sponsored health insurance. MAIN OUTCOME MEASURES: Change in percent uninsured,
      change in per capita total tax payments. RESULTS: The per capita cost of a state
      specific program is directly related to current uninsured rates, $130 in states
      with low uninsured rates (10%) to $230 in states with high uninsured rates (21%).
      This would represent increases in state total tax effort of 10% to 19%,
      respectively. In contrast, equal tax effort to finance a national program would
      imply per capita yields of about $200 in the low-uninsured states and about $150
      in the high-uninsured states. CONCLUSIONS: Substantial state tax effort would be
      necessary to cover the low-income uninsured-especially in states with the highest
      uninsured rates, which also have the lowest tax capacity. Targeted federal
      financial assistance may be necessary, if policymakers wish to induce many states
      to provide health insurance coverage for their uninsured.

PMID- 9256227
TI  - Epstein-Barr virus and the immune system. Hide and seek.

PMID- 9256229
TI  - The platelet, the patient, and periprocedural infarction during percutaneous
      transluminal coronary angioplasty.

PMID- 9256230
TI  - Major teaching hospitals defying Darwin.

PMID- 9256231
TI  - The role of the 'Rieske' iron sulfur protein in the hydroquinone oxidation (Q(P))
      site of the cytochrome bc1 complex. The 'proton-gated affinity change' mechanism.
AB  - The essential reaction in the widely accepted proton-motive Q-cycle mechanism of
      the bc1 complex is the bifurcation of the electron flow during hydroquinone
      oxidation at the hydroquinone oxidation (Q(P)) site formed by the 'Rieske' iron
      sulfur protein and by the heme bL domain of cytochrome b. The 'Rieske' [2Fe-2S]
      cluster has a unique structure containing two exposed histidine ligands, which
      are the binding site for quinones. The affinity of the 'Rieske' cluster for
      quinones increases several orders of magnitude upon reduction; this will
      stabilize semiquinone at the Q(P) site. Based on this affinity change, a reaction
      scheme is presented which can explain the bifurcation of the electron flow
      without invoking highly unstable semiquinone species.

PMID- 9256232
TI  - Involvement of cyanide-resistant and rotenone-insensitive pathways of
      mitochondrial electron transport during oxidation of glycine in higher plants.
AB  - Metabolism of glycine in isolated mitochondria and protoplasts was investigated
      in photosynthetic, etiolated (barley and pea leaves) and fat-storing (maize
      scutellum) tissues using methods of [1-(14)C]glycine incorporation and counting
      of 14CO2 evolved, oxymetric measurement of glycine oxidation and rapid
      fractionation of protoplasts incubated in photorespiratory conditions with
      consequent determination of ATP/ADP ratios in different cell compartments. The
      involvement of different paths of electron transport in mitochondria during
      operation of glycine decarboxylase complex (GDC) was tested in different
      conditions, using aminoacetonitrile (AAN), the inhibitor of glycine oxidation in
      mitochondria, rotenone, the inhibitor of Complex I of mitochondrial electron
      transport, and inhibitors of cytochrome oxidase and alternative oxidase. It was
      shown that glycine has a preference to other substrates oxidized in mitochondria
      only in photosynthetic tissue where succinate and malate even stimulated its
      oxidation. Rotenone had no or small effect on glycine oxidation, whereas the role
      of cyanide-resistant path increased in the presence of ATP. Glycine oxidation
      increased ATP/ADP ratio in cytosol of barley protoplasts incubated in the
      presence of CO2, but not in the CO2-free medium indicating that in conditions of
      high photorespiratory flux oxidation of NADH formed in the GDC reaction passes
      via the non-coupled paths. Activity of GDC in fat-storing tissue correlated with
      the activity of glyoxylate-cycle enzymes, glycine oxidation did not reveal
      preference to other substrates and the involvement of paths non-connected with
      proton translocation was not pronounced. It is suggested that the preference of
      glycine to other substrates oxidized in mitochondria is achieved in
      photosynthetic tissue by switching to rotenone-insensitive intramitochrondrial
      NADH oxidation and by increasing of alternative oxidase involvement in the
      presence of glycine.

PMID- 9256233
TI  - Ion channels formed in planar lipid bilayers by Bacillus thuringiensis toxins in
      the presence of Manduca sexta midgut receptors.
AB  - A purified, GPI-linked receptor complex isolated from Manduca sexta midgut
      epithelial cells was reconstituted in planar lipid bilayers. CryIAa, CryIAc and
      CryIC, three Bacillus thuringiensis insecticidal proteins, formed channels at
      much lower doses (0.33-1.7 nM) than in receptor-free membranes. The non-toxic
      protein CryIB also formed channels, but at doses exceeding 80 nM. The channels of
      CrylAc, the most potent toxin against M. sexta, rectified the passage of cations.
      All other toxin channels displayed linear current-voltage relationships.
      Therefore, reconstituted Cry receptors catalyzed channel formation in
      phospholipid membranes and, in two cases, were involved in altering their
      biophysical properties.

PMID- 9256234
TI  - Nuclear levels of NF-kappaB correlate with syncytium-forming capacity of 8e51
      cells, expressing a defective HIV virus.
AB  - The double NF-kappaB site identified in the LTR of the human immunodeficiency
      virus-1 (HIV-1) has been demonstrated to be necessary for efficient viral
      transcription. In this report we present the characterisation of NF-kappaB
      subunits engaged in complexes binding to the HIV-1 NF-kappaB site in human 8e51 T
      cells, that harbour a defective HIV-1. At least four different specific NF-kappaB
      complexes are present in the nucleus of these cells. With the use of specific
      antibodies we have determined the composition of each complex using
      electrophoretic mobility shift assays. The results show the presence of several
      NF-kappaB family members, with the transactivating RelA being engaged in multiple
      complexes. The importance of NF-kappaB complexes in viral functions has been
      established comparing the level of NF-kappaB DNA-binding complexes with syncytia
      forming activity of 8e51 cells. In fact, 8e51 cells that had almost lost their
      syncytia-forming capacity were found to contain at least 10 times less active NF
      kappaB DNA-binding complex than the actively fusing cells. The correlation is
      specific as the level of at least three other transcription factors did not
      change.

PMID- 9256235
TI  - Fungal cleavage of thioether bond found in Yperite.
AB  - The degradation of thiodiglycol (I) and benzyl sulfide (II) was attempted using
      Coriolus versicolor and Tyromyces palustris to investigate the potential ability
      of basidiomycetes to degrade Yperite (bis(2-chloroethyl) sulfide), a mass
      produced and stored chemical warfare agent. I was very rapidly degraded by both
      fungi. The metabolic pathway of II was elucidated, showing that the initial step
      was the hydrolytic cleavage of the thioether bond to yield benzyl alcohol and
      benzyl mercaptan. Benzyl alcohol was further oxidized and finally mineralized.
      Benzyl mercaptan is reversibly converted to benzyl disulfide and also converted
      to benzyl alcohol. Finally, the effective degradation of bis(2-bromoethyl)
      sulfide strongly suggests that basidiomycete would be a potential tool for
      Yperite degradation.

PMID- 9256236
TI  - Differential action of AGCF2 upon cell type-dependent expression of human
      angiotensinogen gene.
AB  - To investigate the regulatory mechanisms of human angiotensinogen (ANG) gene
      expression in the brain, we analyzed the 1.3-kb promoter by transfection studies
      and gel shift assays. The region from -106 to +44 was sufficient for promoter
      activity in glioblastoma cells, and multiple nuclear factors including AGCF2
      (human ANG core promoter binding factor 2) bound within this 150-bp region. The
      mutations within AGCF2-binding elements decreased the transcriptional activity in
      glioblastoma cells but rather increased it in hepatoma cells. These results
      indicate that AGCF2 has a differential function between these cells and
      contributes to the glia-dependent angiotensinogen promoter activity.

PMID- 9256238
TI  - Dramatic enhancement of the catalytic activity of coagulation factor IXa by
      alcohols.
AB  - The coagulation factor IXa (FIXa) exhibits a very weak proteolytic activity
      towards natural or synthetic substrates. Upon complex formation with its cofactor
      FVIIIa and Ca2+-mediated binding to phospholipid membranes, FIXa becomes a very
      potent activator of FX. The presence of FVIIIa has no effect on the cleavage of
      peptide substrates by FIXa, however. We found that several alcohols dramatically
      enhance the catalytic activity of human FIXa towards synthetic substrates.
      Substrates with the tripeptidyl moiety R-D-Xxx-Gly-Arg are especially susceptible
      to the enhanced FIXa catalysis. Maximal increase up to 20-fold has been measured
      in the presence of ethylene glycol. We suggest that alcohols modify the
      conformation of FIXa rendering the active-site cleft more easily accessible to
      tripeptide substrates with a hydrophobic residue in the P3-position.

PMID- 9256239
TI  - Effect of excess cadmium ion on the metal binding site of cabbage histidinol
      dehydrogenase studied by 113Cd-NMR spectroscopy.
AB  - The enzymatic reaction of histidinol dehydrogenase (HDH) was stimulated by about
      maximally 75% on the addition of Cd2+ ion to the reaction mixture. 113Cd
      substituted HDH in the presence of excess Cd2+ has been studied by 113Cd-NMR.
      113Cd2+ less than 1 equiv. per subunit preferentially binds to the catalytic
      metal binding site of the apoenzyme. Further addition of the metal ions causes
      the structural change of the enzyme including the catalytic metal binding site.
      HDH takes at least three discernible states, which may correspond to the more or
      less active forms of the enzyme induced by metal ions.

PMID- 9256237
TI  - Activation of mitogen-activated protein kinase by the nociceptin receptor
      expressed in Chinese hamster ovary cells.
AB  - Activation of the nociceptin receptor stably expressed in Chinese hamster ovary
      cells induced a transient mitogen-activated protein kinase (MAPK) activation, via
      pertussis toxin-sensitive G-proteins. The nociceptin receptor-mediated MAPK
      activation was partially blocked by down-regulation or inhibition of protein
      kinase C, and suppressed by pretreatment with a phosphatidylcholine-specific
      phospholipase C inhibitor, D609. Furthermore, a tyrosine protein kinase
      inhibitor, genistein, and phosphatidylinositol 3-kinase inhibitors, wortmannin
      and LY294002, affected the nociceptin-induced MAPK activity. The nociceptin
      induced MAPK activation may lead to activation of phospholipase A2 and induce
      changes in gene expression.

PMID- 9256240
TI  - Interpretation of the reactivity of peroxidase compounds I and II with phenols by
      the Marcus equation.
AB  - The catalytic cycle of heme peroxidases involves two reactive states, compound I
      and compound II. Although their reduction potentials at pH 7 are similar,
      compound I is in general more reactive towards organic substrates than compound
      II. The different reactivities have until now remained unexplained. In this
      study, the reactions of compounds I and II of peroxidase from horseradish with
      phenols were analyzed using the Marcus equation of electron-transfer. Both
      reactions exhibit similar reorganization energies, and the different reactivities
      of the two enzyme states can be ascribed to a higher apparent rate of
      activationless electron-transfer in the compound I reactions. This can be
      attributed to the shorter electron-tunneling distance on electron-transfer to the
      porphyrin radical cation in compound I, compared to electron-transfer to the iron
      ion in compound II.

PMID- 9256241
TI  - Unique protein kinase C profile in mouse oocytes: lack of calcium-dependent
      conventional isoforms suggested by rtPCR and Western blotting.
AB  - rtPCR and Western blotting were used to determine which members of the PKC family
      are present in both immature and mature mouse oocytes. Using isoform-specific PCR
      primers and antibodies PKC-delta and -lambda were detected while such techniques
      failed to observe the conventional isoforms of PKC-alpha, -beta, -gamma. This
      isoform profile was confirmed using an alternative PCR strategy, which allowed
      discrimination of PCR products derived from conventional and novel PKC isoforms.
      In addition PKC-epsilon, -eta, -theta and -zeta were not detected by rtPCR. These
      results suggest that the predominant isoforms in oocytes are PKC-delta and 
      lambda.

PMID- 9256242
TI  - Alkyl lysophospholipids inhibit phorbol ester-stimulated phospholipase D activity
      and DNA synthesis in fibroblasts.
AB  - The antineoplastic alkyl lysophospholipids (ALP) 1-O-octadecyl-2-O-methyl-rac
      glycero-3-phosphocholine (ET-18-OCH3) and 1-S-hexadecylthio-2-methoxymethyl-2
      deoxy-rac-glycero-3-phosphocho line (BM41.440) were found to alter phospholipase
      D (PLD)-mediated phosphatidylcholine (PtdCho) and phosphatidylethanolamine
      (PtdEtn) hydrolysis in NIH 3T3 fibroblasts. After a shorter (50 min) treatment,
      2.5-7.5 microg/ml concentrations of ALP stimulated PtdCho, but not PtdEtn,
      hydrolysis 2-4-fold. At the same time, 7.5-25 microg/ml concentrations of ALP
      significantly inhibited the larger (5.8-6.5-fold) stimulatory effects of phorbol
      12-myristate 13-acetate (PMA) on both PtdCho and PtdEtn hydrolysis. When a brief
      (30 min) exposure of cells to 1-2.5 microg/ml concentrations of BM 41.440 was
      followed by incubation of washed cells for 3-16 h prior to the assay of PLD
      activity or DNA synthesis, the treated cells exhibited no increased PtdCho
      hydrolysis, while their responses to the stimulatory PMA effects on both PLD
      activity and DNA synthesis were strongly reduced. The results suggest that the
      PLD and protein kinase C systems may be important cellular targets of ALP
      actions.

PMID- 9256243
TI  - The 58 kDa mouse selenoprotein is a BCNU-sensitive thioredoxin reductase.
AB  - The flavoprotein thioredoxin reductase [EC 1.6.4.5] (NADPH + H+ + thioredoxin-S2 
      -> NADP+ + thioredoxin-(SH)2) was isolated from mouse Ehrlich ascites tumour
      (EAT) cells. Like the counterpart from human placenta but unlike the known
      thioredoxin reductases from non-vertebrate organisms, the mouse enzyme was found
      to contain 1 equivalent of selenium per subunit of 58 kDa. The K(M) values were
      4.5 microM for NADPH, 480 microM for DTNB and 36 microM for Escherichia coli
      thioredoxin, the turnover number with DTNB being approximately 40 s(-1). As mouse
      is a standard animal model in cancer and malaria research, thioredoxin reductase
      and glutathione reductase [EC 1.6.4.2] from EAT cells were compared with each
      other. While both enzymes in their 2-electron reduced form are targets of the
      cytostatic drug carmustine (BCNU), no immunologic cross-reactivity between the
      two mouse disulfide reductases was observed.

PMID- 9256244
TI  - Mutational analysis of the mouse 5-HT7 receptor: importance of the third
      intracellular loop for receptor-G-protein interaction.
AB  - The mouse serotonin (5-HT) receptor subtype, 5-HT7, belongs to the family of
      seven transmembrane G-protein-coupled receptors. To identify the structural basis
      for the coupling of 5-HT7 receptor to G alpha(s) we constructed a number of
      receptor mutants in which amino acid residues were either substituted or deleted
      from the second and third intracellular loops. Wild-type and mutant 5-HT7
      receptors were expressed in insect cells using the baculovirus vectors. Two
      mutant receptor species, 5-HT7(E325G) and 5-HT7(K327S), demonstrated markedly
      impaired abilities to stimulate adenylyl cyclase. The results suggest the
      importance of the C-terminal region of the third intracellular loop in receptor-G
      protein interaction and that specific charged residues, E325 and K327, may play a
      critical role in this interaction.

PMID- 9256245
TI  - Isolation of several human axonemal dynein heavy chain genes: genomic structure
      of the catalytic site, phylogenetic analysis and chromosomal assignment.
AB  - Dynein heavy chains (DHCs) are the main components of multisubunit motor ATPase
      complexes called dyneins. Axonemal dyneins provide the driving force for ciliary
      and flagellar motility. Recent molecular studies demonstrated that multiple DHC
      isoforms are produced by separate genes. We describe the isolation of five human
      axonemal DHC genes. Analysis of the human genomic clones revealed the existence
      of intronic sequences that were used to demonstrate that human axonemal DHC genes
      are located on different chromosomes. The cloned human DHC sequences were
      integrated into an evolutionary approach based on phylogenetic analysis. Tissue
      expression studies showed that these human axonemal DHCs are expressed in testis
      and/or trachea, two tissues with axonemal structures that can be altered in
      primary ciliary dyskinesia, making DHC genes strong candidates in the genesis of
      these human diseases.

PMID- 9256246
TI  - Mapping the ubiquitin-binding domains in the p54 regulatory complex subunit of
      the Drosophila 26S protease.
AB  - Short-lived intracellular proteins, after being marked by multiubiquitination,
      are degraded by the 26S protease. This large ATP-dependent protease is composed
      of two multiprotein complexes: the regulatory complex and the 20S proteosome. The
      selective recognition of ubiquitinated proteins is ensured by the regulatory
      complex. Using an overlay assay a single 54-kDa multiubiquitin-chain-binding
      subunit was detected in the regulatory complex of the Drosophila 26S protease.
      Overlay assay with the recombinant p54 subunit confirmed its ubiquitin-binding
      property. The recombinant protein showed pronounced preference for higher
      ubiquitin multimers, in agreement with the known preference of the 26S protease
      for multiubiquitinated proteins as substrates. To map the ubiquitin-binding
      domain of the p54 subunit different segments of the recombinant protein were
      expressed in E. coli and tested by the overlay assay. The p54 subunit carries two
      independent ubiquitin-binding domains. The central domain carries two highly
      conserved sequence blocks: the FGVDP sequence (at position 207), which is 100%
      conserved from yeast till human, and the DPELALALRVSMEE sequence (at position
      214), which is 100% conserved in higher eukaryotes with two amino acid changes in
      yeast. In the C-terminal ubiquitin-binding domain the GVDP sequence motif is
      repeated and 100% conserved in higher eukaryotes. This domain, however, due to
      the shorter size of the yeast multiubiquitin-binding subunit, is present only in
      higher eukaryotes.

PMID- 9256247
TI  - A novel compound, 1,1-dimethyl-5(1-hydroxypropyl)-4,6,7-trimethylindan, is an
      effective inhibitor of the tet(K) gene-encoded metal-tetracycline/H+ antiporter
      of Staphylococcus aureus.
AB  - A novel indan derivative, 1,1-dimethyl-5-(1-hydroxypropyl)-4,6,7-trimethylindan
      (Ro 07-3149), was found to be a strong inhibitor of the tet(K) gene-encoded
      tetracycline/H+ antiporter of Staphylococcus aureus. One micromole of this
      compound per mg membrane protein was enough for complete inhibition of the Tet(K)
      mediated tetracycline transport and tetracycline-coupled proton transport,
      without the energy state of the membrane being affected. The mode of inhibition
      was non-competitive. Although this compound caused membrane de-energization at a
      high concentration, the IC50 value for de-energization (7.3 micromol/mg membrane
      protein) was about 17 times and 33 times higher than the values for Tet(K)
      mediated proton/tetracycline antiport and [3H]tetracycline transport,
      respectively, indicating that the inhibitory action of Ro 07-3149 is not due to
      the uncoupling effect of the inhibitor.

PMID- 9256248
TI  - The recognition of haemoglobin by antibodies raised for the immunoassay of beta
      amyloid.
AB  - Canine and porcine cerebrospinal fluid (CSF) were fractionated by size exclusion
      chromatography and analysed by a luminescence enzyme linked immunosorbent assay
      (ELISA) configured to detect beta-amyloid. A peak of activity was observed in the
      CSF consistent with the molecular weight of beta-amyloid. When CSF contaminated
      with blood was analysed an additional peak of immunoreactivity at a higher
      molecular weight was observed. The peak of activity was found to be derived from
      cross-reactivity of the immunoglobulins employed in the ELISA with haemoglobin.
      These findings are discussed with reference to primary and structural sequence
      homology between beta-amyloid and haemoglobin from a number of species, the known
      properties of beta-amyloid and recent clinical reports.

PMID- 9256249
TI  - Crystallization, preliminary diffraction and electron paramagnetic resonance
      studies of a single crystal of cytochrome P450nor.
AB  - Cytochrome P450nor (P450nor) is a heme-containing nitric oxide reductase from the
      denitrifying fungus, Fusarium oxysporum. This enzyme catalyzes the reduction of
      NO to N2O. In the present study, we report results from preliminary
      crystallographic and electron paramagnetic resonance (EPR) analysis of a single
      crystal of P450nor. The crystal was grown in 100 mM MES buffer at pH 5.6 using
      PEG 4000 as a precipitant. It belongs to the orthorhombic system with cell
      dimensions of a = 54.99 A, b = 82.66 A, c = 87.21 A, and the space group is
      P2(1)2(1)2(1). The crystal diffracts synchrotron radiation at higher than 2.0 A
      resolution, and therefore it is suitable for X-ray crystal structure analysis at
      atomic resolution. Bijvoet and dispersive anomalous difference Patterson maps
      show a clear peak corresponding to the heme iron. The structure solution is
      currently underway by means of MIR and MAD techniques. EPR analysis determined
      the orientation of the heme within the P450nor crystal.

PMID- 9256250
TI  - Mutations in subunit 6 of the F1F0-ATP synthase cause two entirely different
      diseases.
AB  - A lowered efficiency of oxidative phosphorylation was recently found in a Leber
      hereditary optic neuropathy (LHON) proband carrying a mutation in the mtDNA gene
      for subunit 6 of the membrane-bound F0 segment of the F1F0-ATP synthase [9]. This
      phenotype was transferred to cytoplasmic hybrid cells together with the mutation,
      proving its functional significance. Increasing the respiratory rate in the
      mitochondria from this mutant raised the ATP/2e- ratio back to normal values. A
      different mutation in the same mtDNA gene has been found in patients with the
      NARP syndrome [10]. Although the ATP/2e- ratio is also decreased in this mutant,
      in this case an increase in the respiratory rate could not compensate for it.
      Whilst both mutations affect subunit 6 of the proton-translocating F0 segment,
      the LHON mutation induces a proton leak whereas the NARP mutation blocks proton
      translocation. Hence, the latter will have much more destructive metabolic
      consequences in agreement with the large clinical differences between the two
      diseases.

PMID- 9256251
TI  - The presence of a transcription activation function in the hormone-binding domain
      of androgen receptor is revealed by studies in yeast cells.
AB  - To assess the importance of various regions of the androgen receptor (AR) in
      transcriptional regulation, we have compared its activation functions (AFs) in
      yeast and mammalian cells. The receptor's amino-terminal region contains a major
      transcriptional activator (AF-1) in both cell types, whereas AF-2 in the ligand
      binding domain (LBD) is very weak in mammalian cells but clearly functional in
      the yeast. Hormone-binding ability of LBD is mandatory for AF-2 to operate, as
      illustrated by mutated LBD constructs. The activity of AF-2 in yeast is severely
      attenuated when the hinge region is attached to LBD, suggesting that the former
      region modulates AF-2 in vivo, probably by presenting an interface for
      interacting proteins.

PMID- 9256252
TI  - The complete mature bovine prion protein highly expressed in Escherichia coli:
      biochemical and structural studies.
AB  - According to the 'protein only' hypothesis, modification of the 3-dimensional
      fold of the constituent cellular protein, PrP(C), into the disease-associated
      isoform, PrP(Sc), is the cause of neurodegenerative diseases in animals and
      humans. Here we describe the high-level synthesis in Escherichia coli, and
      purification in the monomeric form, of a histidine-tagged full-length mature PrP
      (25-249) of bovine brain, termed His-PrP. Based on biochemical and spectroscopic
      data, His-PrP displays characteristics expected for the PrP(C) isoform. The
      reported expression system should allow the production of quantities of bovine
      PrP(C) sufficient to permit 3-dimensional structure determinations.

PMID- 9256253
TI  - Mutagenesis of nitrite reductase from Pseudomonas aeruginosa: tyrosine-10 in the
      c heme domain is not involved in catalysis.
AB  - In Pseudomonas aeruginosa, conversion of nitrite to NO in dissimilatory
      denitrification is catalyzed by the enzyme nitrite reductase (NiR), a homodimer
      containing a covalently bound c heme and a d1 heme per subunit. We report the
      purification and characterization of the first single mutant of P. aeruginosa cd1
      NiR in which Tyr10 has been replaced by Phe; this amino acid was chosen as a
      possibly important residue in the catalytic mechanism of this enzyme based on the
      proposal (Fulop, V., Moir, J.W.B., Ferguson, S.J. and Hajdu, J. (1995) Cell 81,
      369-377) that the topologically homologous Tyr25 plays a crucial role in
      controlling the activity of the cd1 NiR from Thiosphaera pantotropha. Our results
      show that in P. aeruginosa NiR substitution of Tyr10 with Phe has no effect on
      the activity, optical spectroscopy and electron transfer kinetics of the enzyme,
      indicating that distal coordination of the Fe3+ of the d1 heme is provided by
      different side-chains in different species.

PMID- 9256254
TI  - Isolation of mRNAs induced by a hazardous chemical in white-rot fungus, Coriolus
      versicolor, by differential display.
AB  - White-rot fungus Coriolus versicolor, a ligninolytic basidiomycete, has been
      studied because of its ability to degrade hazardous chemicals. In this study, we
      searched for genes that are induced by a hazardous chemical using the mRNA
      differential-display technique and C. versicolor IFO30340 that has been exposed
      to pentachlorophenol (PCP). Five cDNA fragments were cloned and the DNA sequences
      of two fragments were analyzed in further detail. The clones corresponded to
      novel genes that have not previously been identified in C. versicolor. One of the
      cDNAs exhibited strong sequence homology to the gene for an enolase and the other
      exhibited homology to a heat shock protein. The expression of the two genes was
      up-regulated in PCP-treated C. versicolor.

PMID- 9256255
TI  - Synergetic inhibition of photophosphorylation and uncoupled electron transport by
      N,N'-dicyclohexylcarbodiimide and alcohols in pea chloroplasts.
AB  - It is shown that the inhibitory effect of N,N'-dicyclohexylcarbodiimide (DCCD) on
      photophosphorylation and uncoupled electron transfer from H2O to methylviologen
      (MV) in pea chloroplasts depends upon solvent concentration. Being applied as a
      solution in dimethyl sulfoxide (DMSO) DCCD did not suppress uncoupled electron
      transfer and inhibited photophosphorylation independently from DMSO
      concentration. If DCCD was applied as methanolic or ethanolic solution its
      concentration sufficient for half-maximum inhibition [I]50 of both
      photophosphorylation and uncoupled electron transfer decreased at increasing
      alcohol content. The data suggest that the synergistic effect of DCCD and
      alcohols is connected with DCCD-catalyzed etherification of some carboxylic
      groups which are important for chloroplast electron transfer.

PMID- 9256256
TI  - Cloning and expression of an alternatively spliced mRNA encoding a soluble form
      of the human interleukin-6 signal transducer gp130.
AB  - The membrane-bound gp130 glycoprotein acts as an affinity converting and signal
      transducing receptor (R) for interleukin-6 and several other cytokines. In this
      work, we RT-PCR amplified gp130 cDNA using primers flanking the sequence encoding
      the transmembrane domain of gp130. We observed in blood mononuclear cells, in
      addition to the expected 333-bp length fragment, a second major band of 418 bp.
      Sequencing of the 418-bp fragment and its genomic counterpart showed a new 85-bp
      exon located in the sequence encoding the extracellular region of the gp130
      protein. This exon is most likely due to alternative splicing and leads to a
      frame-shift resulting in a stop-codon 1 bp before the transmembrane coding
      region. Correspondingly, supernatants from chinese hamster ovary cells
      transfected with this cDNA contained 4-5 times more soluble (s) gp130 than
      supernatants from cells transfected with a cDNA encoding the membrane-bound gp130
      protein. Both gp130 and alternatively spliced sgp130 were also transcribed by the
      myeloma cell lines XG-1, XG-2, XG-4, XG-4CNTF XG-6, XG-7, XG-9, XG-10, U266 and
      RPMI 8226. However, XG-4A cells derived from XG-4 cells, but growing
      independently of exogenous IL-6, did not transcribe sgp130 mRNA. A possible
      interference with intracrine stimulatory factors by alternatively spliced sgp130
      needs to be further investigated.

PMID- 9256257
TI  - TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and
      the mRNAs encoding peroxisomal proteins in rat liver.
AB  - We have studied the effects of TNF-alpha on the mRNAs coding for the peroxisome
      proliferator activated receptor alpha (PPAR-alpha), and for catalase (Cat), acyl
      CoA oxidase (AOX), multifunctional enzyme (PH), and beta-actin in rat liver.
      Total RNA was isolated from livers of male SD-rats 16 h after administration of a
      single dose of 25 microg TNF-alpha and mRNAs were analyzed by a novel dot blot
      RNase protection assay. The mRNAs for PPAR-alpha and for Cat, AOX and PH were
      significantly reduced by TNF-treatment. In addition, the level of PPAR-alpha
      protein was also decreased after TNF. In contrast, the mRNA for beta-actin was
      markedly increased implying that the effect of TNF on PPAR-alpha and the
      peroxisomal mRNAs is highly selective. This effect may have important
      implications in perturbation of the lipid metabolism induced by TNF-alpha.

PMID- 9256258
TI  - Crystal structure of tetranectin, a trimeric plasminogen-binding protein with an
      alpha-helical coiled coil.
AB  - Tetranectin is a plasminogen kringle 4-binding protein. The crystal structure has
      been determined at 2.8 A resolution using molecular replacement. Human
      tetranectin is a homotrimer forming a triple alpha-helical coiled coil. Each
      monomer consists of a carbohydrate recognition domain (CRD) connected to a long
      alpha-helix. Tetranectin has been classified in a distinct group of the C-type
      lectin superfamily but has structural similarity to the proteins in the group of
      collectins. Tetranectin has three intramolecular disulfide bridges. Two of these
      are conserved in the C-type lectin superfamily, whereas the third is present only
      in long-form CRDs. Tetranectin represents the first structure of a long-form CRD
      with intact calcium-binding sites. In tetranectin, the third disulfide bridge
      tethers the CRD to the long helix in the coiled coil. The trimerization of
      tetranectin as well as the fixation of the CRDs relative to the helices in the
      coiled coil indicate a demand for high specificity in the recognition and binding
      of ligands.

PMID- 9256260
TI  - Research and the researcher.

PMID- 9256259
TI  - X-ray diffraction and far-UV CD studies of filaments formed by a leucine-rich
      repeat peptide: structural similarity to the amyloid fibrils of prions and
      Alzheimer's disease beta-protein.
AB  - The development of neuro-degenerative diseases often involves amyloidosis, that
      is the formation of polymeric fibrillar structures from normal cellular proteins
      or peptides. For example, in Alzheimer's disease, a 42 amino acid peptide
      processed from the amyloid precursor protein forms filaments with a beta-sheet
      structure. Because of this, the structure and dynamics of polymeric peptide
      filaments is of considerable interest. We showed previously that a 23 amino acid
      peptide constituting a single leucine-rich repeat (LRRN) polymerises
      spontaneously in solution to form long filaments of a beta-sheet structure, a
      property similar to that of Alzheimer's beta-amyloid and prion peptides. Here we
      report that a variant of LRRN in which a highly conserved asparagine residue is
      replaced by aspartic acid does not form either filaments or beta structure. By
      contrast, a variant which replaces this asparagine residue with glutamine forms
      filaments ultrastructurally indistinguishable from those of LRRN. Electron
      micrographs of LRRN filaments show that many consist of two interleaved strands
      which appear to have a ribbon-like morphology. X-ray diffraction patterns from
      oriented LRRN fibres reveal that they are composed of long beta-sheet arrays,
      with the interstrand hydrogen bonding parallel to the filament axis. This 'cross
      beta' structure is similar to that adopted by beta-amyloid and prion derived
      fibres. Taken together, these results indicate that the LRR filaments are
      stabilised by inter- or intra-strand hydrogen bonded interactions comparable to
      the asparagine ladders of beta-helix proteins or the 'glutamine zippers' of poly
      glutamine peptides. We propose that similar stabilising interactions may underlie
      a number of characterised predispositions to neuro-degenerative diseases that are
      caused by mutations to amide residues. Our finding that amyloid-like filaments
      can form from a peptide motif not at present correlated with degenerative disease
      suggests that a propensity for beta-filament formation is a common feature of
      protein sub-domains.

PMID- 9256261
TI  - FDA research.

PMID- 9256262
TI  - Live HIV vaccines--how safe?

PMID- 9256263
TI  - Emphysema, lung disease and retinoic acid.

PMID- 9256264
TI  - Researching alternative medicine.

PMID- 9256265
TI  - A putative cellular receptor for dengue viruses.

PMID- 9256266
TI  - Immunostimulatory DNA: a clear and present danger?

PMID- 9256267
TI  - Pain killers of the immune system.

PMID- 9256268
TI  - Taming the sinister side of BMT: Dr. Jekyll and Mr. Hyde.

PMID- 9256269
TI  - Oligonucleotide therapeutics--novel cardiovascular targets.

PMID- 9256270
TI  - Failure of AZT: a molecular perspective.

PMID- 9256271
TI  - BMPs: actions in flesh and bone.

PMID- 9256272
TI  - An old acquaintance resurfaces in human mesothelioma.

PMID- 9256273
TI  - Inhibition of the alloantibody response by CD95 ligand.
AB  - We investigated the effect of Fas/APO1-ligand (CD95L) gene transfer on allogeneic
      immune responses in vivo. A colon carcinoma cell line from BALB/c mice, CT26, was
      stably transfected with a vector encoding mouse CD95L and was inoculated into
      C57BL/6 mice. CD95L expression markedly reduced allogeneic cytotoxic T lymphocyte
      and helper T lymphocyte activity directed toward CT26. Strikingly, expression of
      CD95L on these allogeneic tumors completely inhibited the generation of
      alloantibodies of both IgM and IgG subclasses. Thus, CD95L inhibited alloantibody
      production and conferred localized immune suppression through this mechanism.
      These results provide insight into the role of CD95L in regulating the
      alloantibody response and the generation of local immune responses.

PMID- 9256274
TI  - Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants.
AB  - An adjuvant role for certain short bacterial immunostimulatory DNA sequences
      (ISSs) has recently been proposed on the basis of their ability to stimulate T
      helper-1 (Th1) responses in gene-vaccinated animals. We report here that
      noncoding, ISS-enriched plasmid DNAs or ISS oligonucleotides (ISS-ODNs) potently
      stimulate immune responses to coadministered antigens. The ISS-DNAs suppress IgE
      synthesis, but promote IgG and interferon-gamma (IFN-gamma) production. They
      furthermore initiate the production of IFN-gamma, IFN-alpha, IFN-beta, and
      interleukins 12 and 18, all of which foster Th1 responses and enhance cell
      mediated immunity. Consideration should be given to adding noncoding DNA
      adjuvants to inactivated or subunit viral vaccines that, by themselves, provide
      only partial protection from infection.

PMID- 9256275
TI  - Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid
      P component gene.
AB  - The tissue amyloid deposits that characterize systemic amyloidosis, Alzheimer's
      disease and the transmissible spongiform encephalopathies always contain serum
      amyloid P component (SAP) bound to the amyloid fibrils. We have previously
      proposed that this normal plasma protein may contribute to amyloidogenesis by
      stabilizing the deposits. Here we show that the induction of reactive amyloidosis
      is retarded in mice with targeted deletion of the SAP gene. This first
      demonstration of the participation of SAP in pathogenesis of amyloidosis in vivo
      confirms that inhibition of SAP binding to amyloid fibrils is an attractive
      therapeutic target in a range of serious human diseases.

PMID- 9256276
TI  - Association of simian immunodeficiency virus Nef with cellular serine/threonine
      kinases is dispensable for the development of AIDS in rhesus macaques.
AB  - The nef gene of simian immunodeficiency virus (SIV) is essential for high viral
      load and induction of AIDS in rhesus monkeys. A mutant form of the SIVmac239 Nef,
      which contains changes in a putative SH3-binding domain (amino acids 104 and 107
      have been changed from PxxP to AxxA), does not associate with cellular
      serine/threonine kinases, but is fully active in CD4 downregulation and
      associates with the cellular tyrosine kinase Src. Infection of two rhesus
      macaques with SIVmac239 containing the mutant AxxA-Nef caused AIDS and rapid
      death in both animals. No reversions were observed in the majority of nef
      sequences analyzed from different time points during infection and from lymphatic
      tissues at the time of death. Our findings indicate that the putative SH3-ligand
      domain in SIVmac Nef and the association with cellular serine/threonine kinases
      are not important for efficient replication and pathogenicity of SIVmac in rhesus
      macaques.

PMID- 9256277
TI  - Dengue virus infectivity depends on envelope protein binding to target cell
      heparan sulfate.
AB  - Dengue virus is a human pathogen that has reemerged as an increasingly important
      public health threat. We found that the cellular receptor utilized by dengue
      envelope protein to bind to target cells is a highly sulfated type of heparan
      sulfate. Heparin, highly sulfated heparan sulfate, and the polysulfonate
      pharmaceutical Suramin effectively prevented dengue virus infection of target
      cells, indicating that the envelope protein-target cell receptor interaction is a
      critical determinant of infectivity. The dengue envelope protein sequence
      includes two putative glycosaminoglycan-binding motifs at the carboxy terminus;
      the first could be structurally modeled and formed an unusual extended binding
      surface of basic amino acids. Similar motifs were also identified in the envelope
      proteins of other flaviviridae. Developing pharmaceuticals that inhibit target
      cell binding may be an effective strategy for treating flavivirus infections.

PMID- 9256278
TI  - Zinc alters conformation and inhibits biological activities of nerve growth
      factor and related neurotrophins.
AB  - A role for Zn2+ in a variety of neurological conditions such as stroke, epilepsy
      and Alzheimer's disease has been postulated. In many instances, susceptible
      neurons are located in regions rich in Zn2+ where nerve growth factor (NGF)
      levels rise as a result of insult. Although the interaction of Zn2+ with this
      neurotrophin has previously been suggested, the direct actions of the ion on NGF
      function have not been explored. Molecular modeling studies predict that Zn2+
      binding to NGF will induce structural changes within domains of this neurotrophin
      that participate in the recognition of TrkA and p75NTR. We demonstrate here that
      Zn2+ alters the conformation of NGF, rendering it unable to bind to p75NTR or
      TrkA receptors or to activate signal transduction pathways and biological
      outcomes normally induced by this protein. Similar actions of Zn2+ are also
      observed with other members of the NGF family, suggesting a modulatory role for
      this metal ion in neurotrophin function.

PMID- 9256279
TI  - Reciprocal relation between VEGF and NO in the regulation of endothelial
      integrity.
AB  - Balloon angioplasty disrupts the protective endothelial lining of the arterial
      wall, rendering arteries susceptible to thrombosis and intimal thickening. We
      show here that vascular endothelial growth factor (VEGF), an endothelial cell
      mitogen, is upregulated in medial smooth muscle cells of the arterial wall in
      response to balloon injury. Both protein kinase C (PKC) and tyrosine kinase
      pp60src mediate augmented VEGF expression. In contrast, nitric oxide (NO) donors
      inhibit PKC-induced VEGF upregulation by interfering with binding of the
      transcription factor activator protein-1 (AP-1) to the VEGF promoter. Inhibition
      of VEGF promoter activation suggests that NO secreted by a restored endothelium
      functions as the negative feedback mechanism that downregulates VEGF expression
      to basal levels. Administration of a neutralizing VEGF antibody impaired
      reendothelialization following balloon injury performed in vivo. These findings
      establish a reciprocal relation between VEGF and NO in the endogenous regulation
      of endothelial integrity following arterial injury.

PMID- 9256280
TI  - Antisense targeting of basic fibroblast growth factor and fibroblast growth
      factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor
      growth.
AB  - Unlike normal melanocytes, primary and metastatic human melanomas express high
      levels of basic fibroblast growth factor (bFGF) and fibroblast growth factor
      receptor-1 (FGFR-1) messenger RNA, and expression of these genes is essential in
      sustaining the proliferation of malignant melanomas in vitro. To determine
      whether bFGF and FGFR-1 are also required for tumor formation in these cells,
      liposome-mediated gene transfer was used to deliver episomal vectors containing
      antisense-oriented bFGF or FGFR-1 cDNAs into human melanomas, grown as
      subcutaneous tumors in nude mice. The growth of tumors injected with these
      constructs was completely arrested or the tumors regressed as a result of blocked
      intratumoral angiogenesis and subsequent necrosis. Thus, inhibition of bFGF/FGFR
      1-mediated signaling may open a new avenue for the treatment of advanced-stage
      melanomas.

PMID- 9256281
TI  - In vivo transfection of cis element "decoy" against nuclear factor-kappaB binding
      site prevents myocardial infarction.
AB  - The transcriptional factor nuclear factor-kappaB (NFkappaB) plays a pivotal role
      in the coordinated transactivation of cytokine and adhesion molecule genes that
      might be involved in myocardial damage after ischemia and reperfusion. Therefore,
      we hypothesized that synthetic double-stranded DNA with high affinity for
      NFkappaB could be introduced in vivo as "decoy" cis elements to bind the
      transcriptional factor and to block the activation of genes mediating myocardial
      infarction, thus providing effective therapy for myocardial infarction. Treatment
      before and after infarction by transfection of NFkappaB decoy, but not scrambled
      decoy, oligodeoxynucleotides before coronary artery occlusion or immediately
      after reperfusion had a significant inhibitory effect on the area of infarction.
      Here, we report the first successful in vivo transfer of NFkappaB decoy
      oligodeoxynucleotides to reduce the extent of myocardial infarction following
      reperfusion, providing a new therapeutic strategy for myocardial infarction.

PMID- 9256282
TI  - Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase
      oligonucleotide.
AB  - Graft coronary arteriosclerosis, which limits the long-term survival of allograft
      recipients, is characterized by diffuse intimal thickening composed of
      proliferative smooth muscle cells. We observed that messenger RNA of the cell
      cycle regulatory enzyme cyclin-dependent kinase (cdk) 2 kinase, which mediates
      smooth muscle cell proliferation, was elevated in the thickened intima of
      coronary arteries of murine heterotopic cardiac allografts. We studied the
      effects of antisense phosphorothioate oligodeoxynucleotide (ODN) against this
      enzyme using gene transfer mediated by a hemagglutinating virus of Japan (HVJ)
      liposome complex intraluminally delivered to inhibit the intimal hyperplasia. At
      30 days after transplantation, antisense cdk2 kinase ODN treatment had
      dramatically inhibited neointimal formation in the allografts. Expression of
      vascular cell adhesion molecule-1 was also suppressed by antisense cdk2 kinase.
      However, these effects were not observed in the sense or scrambled ODN-treated
      allografts. Thus, an intraluminal administration of antisense ODN directed to a
      specific cell cycle regulatory gene can inhibit neointimal formation after
      cardiac transplantation.

PMID- 9256283
TI  - The control of microvascular permeability and blood pressure by neutral
      endopeptidase.
AB  - Plasma extravasation from postcapillary venules is one of the earliest steps of
      inflammation. Substance P (SP) and bradykinin (BK) mediate extravasation and
      cause hypotension. The cell-surface enzyme neutral endopeptidase (NEP)
      inactivates both peptides. Thus, absence of NEP may predispose development of
      inflammation and hypotension. We examined these possibilities in mice in which
      the NEP gene was deleted by homologous recombination. There was widespread basal
      plasma extravasation in postcapillary venular endothelia in NEP-/- mice, which
      was reversed by recombinant NEP and antagonists of SP (NK1) and BK (B2)
      receptors. Mean arterial blood pressure was 20% lower in NEP-/- animals, but this
      was unaffected by reintroduction of recombinant NEP and the kinin receptor
      antagonists. The hypotension was also independent of nitric oxide (NO), because
      NEP-/- mice treated with a NO synthase inhibitor remained hypotensive relative to
      the wild type. Thus, NEP has important roles in regulating basal microvascular
      permeability by degrading SP and BK, and may regulate blood pressure set point
      through a mechanism that is independent of SP, BK and NO. The use of NEP
      antagonists as candidate drugs in cardiovascular disease is suggested by the
      blood pressure data reported herein.

PMID- 9256284
TI  - Simian virus-40 large-T antigen binds p53 in human mesotheliomas.
AB  - We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that
      60% of human mesotheliomas contain and express SV40 sequences, results now
      confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F.
      Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus,"
      NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG
      Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant
      to therapy, originates from the serosal lining of the pleural, pericardial and
      peritoneal cavities. The incidence of mesothelioma continues to increase
      worldwide because of exposure to crocidolite asbestos. However, at least 20% of
      mesotheliomas in the United States are not associated with asbestos exposure, and
      only a minority of people exposed to high concentrations of asbestos develop
      mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not
      exposed to asbestos, and/or may render particular individuals more susceptible to
      the carcinogenic effect of asbestos. We investigated whether the expression of
      the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor
      suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its
      ability to bind and to inactivate p53, a cellular protein that when normally
      expressed plays an important role in suppressing tumor growth and in inducing
      sensitivity to therapy. Our findings do not establish a cause-and-effect
      relation, but indicate that the possibility that SV40 contributes to the
      development of human mesotheliomas should be carefully investigated.

PMID- 9256285
TI  - The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40
      large T-antigen in human mesotheliomas.
AB  - The oncoprotein of simian virus-40, SV40 large T-antigen (Tag), is reported to
      target and to inactivate growth suppressive proteins such as the retinoblastoma
      family and p53 (ref. 4, 5), leading to transformation of human cell lines in
      vitro, tumor production in rodents, and detection of Tag in several human cancers
      including mesotheliomas. The retinoblastoma family contains three members, pRb,
      p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent
      manner, have cell growth suppressive properties and bind to specific members of
      the E2F family and various cyclins. Even though mesotheliomas are among the most
      aggressive human cancers, alterations of important cell-cycle "controllers," such
      as the Rb family genes, have never been reported in these tumors. We found the
      presence of SV40-like sequences in 86% of 35 archival specimens of mesothelioma.
      We also demonstrated that SV40 Tag, isolated from frozen biopsies of human
      mesothelioma, binds each of the retinoblastoma family proteins, pRb, p107 and
      pRb2/p130, in four of four specimens. We propose that the tumorigenic potential
      of SV40 Tag in some human mesotheliomas may arise from its ability to interact
      with and thereby inactivate several tumor and/or growth suppressive proteins.

PMID- 9256286
TI  - A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.
AB  - Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell
      viability may contribute to cancer by facilitating the insurgence of mutations
      and by promoting resistance to therapy. Despite the identification of several new
      apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not
      clear whether apoptosis inhibition plays a general role in neoplasia. Here, we
      describe a new human gene encoding a structurally unique IAP apoptosis inhibitor,
      designated survivin. Survivin contains a single baculovirus IAP repeat and lacks
      a carboxyl-terminal RING finger. Present during fetal development, survivin is
      undetectable in terminally differentiated adult tissues. However, survivin
      becomes prominently expressed in transformed cell lines and in all the most
      common human cancers of lung, colon, pancreas, prostate and breast, in vivo.
      Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas
      (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic).
      Recombinant expression of survivin counteracts apoptosis of B lymphocyte
      precursors deprived of interleukin 3 (IL-3). These findings suggest that
      apoptosis inhibition may be a general feature of neoplasia and identify survivin
      as a potential new target for apoptosis-based therapy in cancer and lymphoma.

PMID- 9256288
TI  - A new structural analysis of DNA using statistical models of infrared spectra.

PMID- 9256287
TI  - The bottleneck in AZT activation.
AB  - Nucleoside-based inhibitors of reverse transcriptase were the first drugs to be
      used in the chemotherapy of AIDS. After entering the cell, these substances are
      activated to their triphosphate form by cellular kinases, after which they are
      potent chain terminators for the growing viral DNA. The two main factors limiting
      their efficacy are probably interrelated. These are the insufficient degree of
      reduction of viral load at the commencement of treatment and the emergence of
      resistant variants of the virus. The reason for the relatively poor suppression
      of viral replication appears to be inefficient metabolic activation. Thus, for
      the most extensively used drug, 3'-azido-3'-deoxythymidine (AZT), whereas
      phosphorylation to the monophosphate is facile, the product is a very poor
      substrate for the next kinase in the cascade, thymidylate kinase. Because of
      this, although high concentrations of the monophosphate can be reached in the
      cell, the achievable concentration of the active triphosphate is several orders
      of magnitude lower. Determination of the structure of thymidylate kinase as a
      complex with AZT monophosphate (AZTMP) together with studies on the kinetics of
      its phosphorylation have now led to a detailed understanding of the reasons for
      and consequences of the poor substrate properties.

PMID- 9256289
TI  - Bacterium-host interactions monitored by time-lapse photography.

PMID- 9256290
TI  - Membrane cation and anion transport activities in erythrocytes of hereditary
      spherocytosis: effects of different membrane protein defects.
AB  - Hereditary spherocytosis (HS) is due to different membrane protein defects (i.e.,
      deficiency of spectrin and ankyrin, band 3, or band 4.2). In order to gain new
      insight into the relationships between band 3 function and proteins associated
      with the cytoskeleton, we studied erythrocyte anion transport activity in HS
      characterized by different membrane protein defects. Anion transport activity was
      increased in HS due to partial band 4.2 deficiency or to band 4.2 absence, while
      in HS associated with deficiency of spectrin + ankyrin or band 3, the anion
      transport results were normal or decreased, respectively. Moreover, since HS
      erythrocytes are characterized by an increased Na and a decreased K, we studied
      the principal membrane cation transport pathways. Activity of the Na/K pump was
      increased in all HS studied, while no changes in Na/K/2Cl cotransport and Na/Li
      exchange were evident between control and HS as well as between forms of HS
      associated with different membrane protein defects. K/Cl cotransport activity was
      decreased in all HS studied compared to normal red cells. In all HS, passive
      membrane permeability to Na and K was increased compared to normal erythrocytes.
      The increased Na and the low K content can be attributed to the abnormal membrane
      permeability to cations, which is not related to a specific membrane protein
      defect.

PMID- 9256291
TI  - Hypocholesterolemia in hairy cell leukemia: a marker for proliferative activity.
AB  - Hypocholesterolemia is a well-documented phenomenon associated with a variety of
      hematological malignancies and nonmalignant disorders associated with
      splenomegaly. To determine the incidence of hypocholesterolemia in patients with
      hairy cell leukemia (HCL), we measured the serum cholesterol levels before and
      after a single cycle of 2-chlorodeoxyadenosine (2-CdA) in 46 patients. The mean
      pre-treatment serum cholesterol level was 152.8 mg/dl (range, 60 to 293 mg/dl).
      The mean post-treatment serum cholesterol level was 190.0 mg/dl. This was
      significantly higher than the pre-treatment values (P <0.0001). Twelve patients
      who had previously undergone splenectomy showed a similar response to treatment,
      with a pre-treatment value of 180.0 mg/dl and a post-treatment value of 219.8
      mg/dl (P < 0.0001). However, there was a significant difference in the pre
      treatment serum cholesterol levels in the nonsplenectomized patients (143.0
      mg/dl) compared to the splenectomized patients (180.0 mg/dl) (P < 0.03). The pre
      treatment serum cholesterol did not correlate with the pre-treatment splenic
      index (correlation coefficient = -0.39, P < 0.065). Similarly, there was no
      correlation between the change in splenic index and the change in serum
      cholesterol level post-treatment. These findings suggest that hypocholesterolemia
      in HCL is related to tumor burden and not to splenomegaly alone. Since
      cholesterol is critical to hairy cell metabolism and structure, treatment
      strategies interfering with cholesterol synthesis may be productive.

PMID- 9256292
TI  - Analysis of intramedullary cell density by MRI using the multiple spin-echo
      technique.
AB  - Analysis of the intramedullary cell distribution by magnetic resonance imaging
      (MRI) using conventional techniques involves subjectively interpreting images and
      estimating the cell distribution on the basis of signal intensity
      characteristics. In recent years, attempts have been made to achieve more precise
      analysis by new techniques, including chemical shift imaging. The multiple spin
      echo (MSE) technique offers some advantages over conventional MRI. Since it
      allows measurement of the transverse magnetization decay curve at 32 or more
      points, it is capable of separating several tissue components with different
      relaxation times. In addition, this technique can be used with MRI instruments
      having a static magnetic field as low as 1.0 Tesla. In the present study, the
      intramedullary cell density was assessed by MRI using the MSE technique in 4
      patients with aplastic anemia (AA), 4 patients with myelodysplastic syndrome
      (MDS), and 5 normal subjects. The water component of the marrow (with a short
      relaxation time) and the fat component (with a long relaxation time) were
      separated from each other by analyzing MR images obtained using the MSE
      technique, and the signal intensity ratio of the 2 components was calculated. The
      ratio was significantly higher in the AA group than in the other groups (AA vs.
      MDS, P = 0.0209, AA vs. normal controls, P = 0.0143). The present technique
      appears promising for quantitative assessment of the intramedullary cell density.

PMID- 9256294
TI  - Psychogenic purpura.

PMID- 9256293
TI  - Human D(IIIa) erythrocytes: RhD protein is associated with multiple dispersed
      amino acid variations.
AB  - As a partial D antigen of the Rh blood group system, the D category IIIa
      phenotype occurs mainly in Blacks, but its molecular basis has not been defined.
      Here we describe studies of the D category D(IIIa) and VS+ red blood cells (RBC)
      from two unrelated probands by Southern blot, cDNA PCR, and nucleotide
      sequencing. Rh haplotyping by Sph I restriction fragment length polymorphisms
      indicated that the two probands carried Dce/dCe and Dce/DcE genotypes,
      respectively. Sequence analysis of Rh cDNAs showed that their erythroid cells
      expressed both D and CE transcripts. Nevertheless, the D transcripts were found
      to contain four nucleotide changes scattered in three exons: nt455 A-to-C (exon
      3), nt602 C-to-G (exon 4), nt 654 C-to-G (exon 5), and nt667 T-to-G (exon 5).
      These variations resulted in the following amino acid substitutions
      characteristic of RhCE polypeptides: 152 Asn-to-Thr, 201 Thr-to-Arg, 218 Ile-to
      Met, and 223 Phe-to-Val. The 152Thr and 223Val residues were predicted to reside
      in proximity to the third and fourth extracellular loops, respectively. Together,
      these results establish a correlation of the four amino acid changes in the RhD
      protein with the expression of D(IIIa) as a partial D antigen on the RBC
      membrane. Since the varied nucleotides identified in D(IIIa) all pre-exist in CE,
      they are likely to have originated from CE by templated micro-conversion
      event(s). The identification of a specific nt736 C-to-G transversion in CE in the
      two probands suggests that 245Val may involve the expression of VS antigen.

PMID- 9256295
TI  - Follicular dendritic cell sarcoma mimicking diffuse large cell lymphoma: a case
      report.
AB  - Follicular dendritic cell sarcomas (FDCSs) are rare tumors arising from
      follicular dendritic cells in lymphoid tissue. Fewer than 20 cases have been
      described in the English-language literature. We describe the second case of an
      FDCS with primary liver involvement. The initial diagnosis was lymphoma, and
      appropriate treatment was prescribed. After the initial treatment failed,
      additional biopsy samples were obtained. Standard pathologic analysis and
      immunophenotyping for a panel of monoclonal antibodies were performed on formalin
      fixed paraffin-embedded tissue and frozen sections. The pathologic findings were
      consistent with FDCS, and the specimens showed some of the characteristic
      pathologic features suggestive of this tumor, including multinucleation and a
      spindle pleomorphic morphology. The tumor cells were positive for S-100 protein,
      CD45, CD14, and vimentin. Because of its morphological characteristics, FDCS can
      be confused with other neoplastic entities, such as lymphomas and other solid
      tumors.

PMID- 9256297
TI  - Gamma chain abnormal human fetal hemoglobin variants.

PMID- 9256296
TI  - Plasma cell leukemia evolving into aggressive extramedullary plasmacytoma by
      clonal selection.

PMID- 9256298
TI  - Uncommon cause of severe pancytopenia: toxoplasmosis.

PMID- 9256299
TI  - Isolated choroidal leukemic infiltration during complete remission.

PMID- 9256300
TI  - Therapy-related acute myeloid leukemia with minimal myeloid differentiation (AML
      M0) associated with a t(11;19)(q23;p13.3) translocation.

PMID- 9256302
TI  - Anti-phospholipid-antibody syndrome associated with peripheral T-cell lymphoma.

PMID- 9256301
TI  - Hypofibrinogenemia induced by prednisolone therapy in a patient with chronic
      lymphocytic leukemia complicated with autoimmune hemolytic anemia.

PMID- 9256303
TI  - Atherosclerosis in SLE and Hughes syndrome.

PMID- 9256304
TI  - Dehydroepiandrosterone (DHEA) and lupus erythematosus: an update.

PMID- 9256305
TI  - The concurrence of lupus and fibromyalgia: implications for diagnosis and
      management.

PMID- 9256306
TI  - Heparin-induced osteoporosis in pregnancy.

PMID- 9256307
TI  - Severe reversible cardiomyopathy associated with systemic vasculitis in primary
      Sjogren's syndrome.
AB  - A 40y old woman with primary Sjogren's syndrome developed elevated purpura,
      peripheral neuropathy, muscular tenderness, abdominal pain, heart failure, and
      convulsive spells. The hallmarks of this disease were high titers of anti-Ro
      antibodies and low complement levels in the serum, leukocytoclastic small vessel
      vasculitis in the cutaneous biopsy specimen, and a life threatening clinical
      course. Echocardiography revealed left ventricular hypokinesis with low ejection
      fraction, which is unlike the more common features of cardiomyopathy complicating
      Sjogren's syndrome. The rapidly deteriorating heart failure and other systemic
      complications remitted on pulse corticosteroid and cyclophosphamide therapy. The
      pathogenesis of heart failure, which appeared concurrently with vasculitis and
      was reversed on immunosuppressive therapy, is explained in the context of the
      systemic disease. Leukocytoclastic vasculitis might be at the origin of this rare
      variant of acute, severe but reversible cardiomyopathy in pSS.

PMID- 9256308
TI  - Obstetric outcome in antiphospholipid syndrome.
AB  - The presence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are
      associated with recurring pregnancy loss. Of 387 consecutive patients
      investigated at a Recurring Miscarriage Clinic over a three year period, 63 (16%)
      were positive for LA and ACA or both. Fifty-nine patients by definition were
      classified as having antiphospholipid syndrome and four also had systemic lupus
      erythematosus (SLE). Fifty-three subsequent pregnancies occurred in 63 patients
      and of these 37 ended in a live birth giving an overall livebirth rate of 70%.
      Treatment included low dose aspirin alone in 37 pregnancies and low dose aspirin
      and low molecular weight heparin (LMWH) in 16 pregnancies. The decision for
      treatment was made empirically on past obstetric history and level of LA and ACA,
      and past history of venous thromboembolic disease. Obstetric outcome was worst in
      the group who were positive for both LA and ACA, with a success rate of 53%,
      compared to 72 or 81% in the single parameter groups. Complications in the 37
      successful pregnancies included eight Caesarean sections, four cases of intra
      uterine growth restriction, one case of pregnancy induced proteinuric
      hypertension, one deep vein thrombosis and one pulmonary embolism. Patients with
      antiphospholipid syndrome are at high risk of pregnancy loss as well as maternal
      morbidity, especially thrombo-embolic disease. A randomised prospective
      controlled trial is necessary to determine the optimum therapy for pregnancy
      conservation and thrombprophylaxis.

PMID- 9256309
TI  - A peculiar form of amicrobial pustulosis of the folds associated with systemic
      lupus erythematosus and other auto-immune diseases.
AB  - Amicrobial pustulosis of the folds is a new entity which was initially described
      in association with systemic lupus erythematosus (SLE). We report four cases of
      this rare pustulosis occurring in the course of various auto-immune disorders.
      Dermatological features were similar in all patients. The primary lesions were
      small pustules which coalesced and formed erosive areas underlined with pustular
      lesions. They were localized in the folds. Three of the four patients had also
      isolated pustules on the scalp. Spongiform pustules were histologically present.
      A primary bacterial or fungal infection was ruled out by cultures on appropriate
      media. Serum calcium level was normal. Associated auto-immune diseases were:
      systemic lupus erythematosus, incomplete systemic lupus erythematosus,
      'idiopathic' thrombocytopenic purpura and myasthenia gravis without thymoma (one
      of each). The relationship between this peculiar form of pustulosis and
      autoimmunity remains to be elucidated. The pustulosis did not respond to
      antibiotics but disappeared with systemic or topical corticosteroids.

PMID- 9256310
TI  - Anti-endothelial cell antibodies in systemic autoimmune diseases: prevalence and
      clinical significance.
AB  - OBJECTIVE: To investigate the prevalence and characteristics of anti-endothelial
      cell antibodies (AECA) in a large cohort of patients with several well defined
      systemic autoimmune diseases, in order to determine their relationship with the
      clinical and laboratory features of these diseases. METHODS: Clinical and
      laboratory features of 216 consecutive Caucasian patients were prospectively
      studied. One hundred and seven patients had been diagnosed as having a primary
      systemic vasculitis-specifically, 39 had temporal arteritis (TA), 25
      polyarteritis nodosa (PAN), 9 Wegener's granulomatosis (WG), and 34 Behcet's
      disease (BD)-, 90 patients had systemic lupus erythematosus (SLE), and 19 had a
      primary Sjogren's syndrome (SS). The AECA were determined by ELISA. RESULTS: One
      hundred and four (48%) patients with systemic autoimmune diseases were found to
      have a positive titre of AECA. Specifically, AECA were detected in 41 (38%)
      patients with a primary systemic vasculitis (13 (33%) with TA, 14 (56%) with PAN,
      5 (56%) with WG and 9 (26%) with BD), in 58 (63%) patients with SLE, and in 5
      (26%) patients with a primary SS. In patients with a primary systemic vasculitis,
      those with AECA were found to have an increased prevalence of disease activity (P
      < 0.05). In SLE patients, those with AECA were found to have an increased
      prevalence of vascular lesions (P < 0.05), lupus nephropathy (P < 0.05), and
      anticardiolipin antibodies (aCL) (P < 0.001). CONCLUSIONS: Patients with systemic
      autoimmune diseases have a high prevalence of AECA and they are associated with
      the presence of vascular lesions, nephropathy, and aCL in SLE, as well as with
      disease activity in several primary systemic vasculitis (TA, PAN, WG and BD).

PMID- 9256311
TI  - Lack of linkage between anti-nuclear antibody or clinical features of systemic
      lupus erythematosus (SLE) and TCR-A/Vbeta loci in families of subjects with SLE.
AB  - The role of the TCR-A and TCR-Vbeta genes in the genetic predisposition to SLE
      expression and anti-nuclear antibody (ANA) production were examined by linkage
      analysis in eighteen multiplex and forty-three simplex SLE families. All subjects
      were Caucasian. A significantly increased prevalence of positive ANAs in first
      degree relatives of SLE patients from multiplex families was noticed compared to
      that of simplex families. Linkage between TCR-A/Vbeta genes and SLE expression
      and ANA production were analysed by affected sib-pair method. Results showed that
      the haplotypes identical by descent sharing TCR-A and TCR-Vbeta genes in the
      affected sib-pairs was not different from that expected (P = 0.93 and P = 0.74,
      respectively). There was no linkage between ANA positivity and TCR-A and TCR
      Vbeta genes in ANA positive sib-pairs from both multiplex and simplex families.
      This study suggests that germline TCR-A and TCR-Vbeta gene loci confer no
      susceptibility to ANA and SLE expression.

PMID- 9256312
TI  - Dyslipoproteinemias in systemic lupus erythematosus: influence of disease,
      activity, and anticardiolipin antibodies.
AB  - OBJECTIVE: To determine the influence of systemic lupus erythematosus (SLE),
      disease activity, and anticardiolipin antibodies (aCL) on lipid profile, in order
      to identify patients with high risk for coronary artery disease (CAD). METHODS:
      Fasting lipid profiles were performed in 36 consecutive female SLE patients
      without any therapy and 30 controls. Exclusion criteria were diabetes mellitus,
      CAD, liver or thyroid disease, ingestion of lipid-raising drugs, serum creatinine
      > or = 1.5 mg/dl, and proteinuria > or = 0.5 g/d. Disease activity was measured
      by SLEDAI. RESULTS: High levels of VLDL-C and TG and low levels of HDL-C, the
      'lupus pattern', were observed in inactive SLE compared to controls (P < 0.05).
      Active disease enhanced this difference inducing a more striking increase in VLDL
      C and TG levels and also a decrease in HDL-C and LDL-C levels compared to
      inactive SLE patients (P < 0.05), characterizing the 'active lupus pattern'.
      Moreover, a significant correlation was found between SLEDAI scores and all lipid
      fractions. Furthermore these lipid abnormalities were particularly associated
      with vasculitis. Lower HDL-C levels detected in IgG aCL+ patients compared to IgG
      aCL- patients were not confirmed by two-way analysis of variance which
      demonstrated that this difference was exclusively caused by disease activity.
      CONCLUSIONS: Our findings suggest that SLE patients have a lipid profile
      abnormality which is aggravated by disease activity and may reside in a defect of
      VLDL metabolism. This pattern of dyslipoproteinemia may increase the risk of
      developing coronary artery disease.

PMID- 9256313
TI  - Autoimmune aberration in sudden sensorineural hearing loss: association with anti
      cardiolipin antibodies.
AB  - In view of the presence of autoantibodies against inner ear antigens, the
      pathogenesis of sudden deafness (SD) and progressive sensorineural hearing loss
      (PSNHL) is suggested to be of an autoimmune nature. However, microthrombosis of
      the inner ear may result from pathogenic anti-cardiolipin antibody (aCL)
      activity. We studied 30 patients (17 females and 13 males, age range 20-52 y), of
      whom 11 suffered from SD and 19 from PSNHL. All were clinically and serologically
      evaluated for association with autoimmune disorders (serological examination
      included: aCL, ANA, ENA, ANCA, proteinelectrophoresis, and complement levels).
      Twenty healthy matched subjects served as controls. None of the control group
      were aCL positive, whereas 8 out of 30 (27%) patients demonstrated low-moderate
      titers (P < 0.02), of whom 5 out of 8 suffered from SD. In addition, 2 aCL
      negative patients with PSNHL demonstrated hypergammaglubolinemia accompanied by
      hypocomplementemia, whereas none with SD had such abnormalities. Our data
      suggests that aCL is detected in patients with sudden sensorineural hearing loss
      and therefore may play an important role in the pathogenesis of this disability.
      If sustained by additional studies, these findings would warrant the
      consideration of anticoagulant therapy.

PMID- 9256314
TI  - Hepatitis B and C viruses serology in patients with SLE.
AB  - Sera of 95 patients with SLE were tested for the presence of hepatitis B surface
      antigen (HBsAg) and anti-hepatitis C antibodies. The results show that HBsAg was
      not detected in the sera of all of the SLE patients. Only one patient was
      confirmed to have anti-HCV antibodies, suggesting that chronic infection with
      hepatitis B and C is not increased in patients with SLE compared with the general
      population.

PMID- 9256315
TI  - Autologous marrow stem cell transplantation for severe systemic lupus
      erythematosus of long duration.
AB  - A 46 year woman with severe long-lasting SLE received an autologous bone marrow
      transplantation utilising CD34+ haematopoietic progenitors following a 3log T
      lymphocyte depletion. The immunosuppressive regimen (conditioning) consisted of
      15mg/kg Thiotepa followed by 100 mg/kg of cyclophosphamide over 2d. Granulocytic
      recovery was aided by G-CSF. The post-transplant course was uneventful, and a
      good clinical and immunologic remission (ANA negativisation) was achieved. This
      is the first case of SLE having received an autologous progenitor cell transplant
      for the autoimmune disease by itself, unaccompanied by a haematologic condition
      requiring transplantation. The potential, advantages and limits of this
      procedure, which are currently being explored worldwide, are briefly discussed.

PMID- 9256316
TI  - Central vein thrombosis in the antiphospholipid syndrome.
AB  - We report the case of a 38 y old man with antiphospholipid syndrome and
      exceptionally extensive central vein thrombosis in the right internal jugular
      vein, superior vena cava, and both subclavian veins. In spite of intensive
      anticoagulation therapy there was only a partial response. We suggest the MR
      angiography be the reference standard for diagnosis in this type of patient.

PMID- 9256317
TI  - Hepatic necrosis and haemorrhage in pregnant patients with antiphospholipid
      antibodies.
AB  - Two case reports of pregnant patients with antiphospholipid antibodies and HELLP
      syndrome (hemolysis, elevated liver enzymes and low platelets) are presented.
      Attention is mainly drawn to the hepatic necrosis and the underlying
      pathophysiology.

PMID- 9256318
TI  - Thrombosis associated with antiphospholipid antibody in juvenile chronic
      arthritis.
AB  - Anticardiolipin antibodies (aCL) have been reported in patients with juvenile
      chronic arthritis (JCA) without associated thrombotic events. We describe a
      patient with longstanding JCA who developed central retinal vein occlusion in the
      presence of antiphospholipid antibodies (APL).

PMID- 9256319
TI  - Ribozyme-mediated cancer gene therapy.

PMID- 9256320
TI  - Preoperative imaging for parathyroid localization in primary hyperparathyroidism.
AB  - BACKGROUND: We retrospectively studied the results of diagnostic imaging using 3
      different modalities to determine their usefulness for preoperative localization
      of the parathyroid, and whether accurate preoperative localization information
      could be used to modify the surgical approach for parathyroidectomy in patients
      with primary hyperparathyroidism. METHODS: Images of 37 parathyroid adenomas or
      hyperplasias in 35 patients with primary hyperparathyroidism were obtained using
      ultrasonography, computed tomography, and subtraction scintigraphy (using
      thallium 201 [thallous chloride] and either iodine 123 or technetium 99m
      pertechnetate [99mTcO4-]). RESULTS: Approximately three fourths of the adenomas
      or hyperplasias were successfully identified by ultrasound (76.7%) and computed
      tomography (76.4%), even when the weight of the tumor was less than 500 mg.
      However, subtraction scintigraphy was of limited use (61.3% successfully
      identified). A combination of these modalities gave excellent results for
      detecting adenomas and hyperplasias, leading to an accurate prediction rate of
      96.0%. CONCLUSION: We conclude that using the combination of these 3 imaging
      modalities is very useful for the detection of parathyroid adenomas and
      hyperplasias, and that with such accurate localization information, the
      unilateral approach alone, or even simple excision of the parathyroid tumors
      might be feasible, enabling less invasive surgical treatment.

PMID- 9256321
TI  - Inhalation of interleukin-2 combined with subcutaneous administration of
      interferon for the treatment of pulmonary metastases from renal cell carcinoma.
AB  - BACKGROUND: Interleukin-2 is the most promising antitumor agent for advanced
      renal cell carcinoma, but systemic immunotherapy with interleukin-2 might be
      limited because of inadequate efficacy and severe adverse effects. In this study,
      we treated 7 patients with lung metastases from renal cell carcinoma with topical
      application of interleukin-2 by inhalation. METHODS: Patients received 100,000 IU
      of interleukin-2 by inhalation 4 times a day and 9,000,000 IU of interferon-alfa
      2a subcutaneously for 5 consecutive days per week. They also received, by oral
      administration, 800 mg of cimetidine and 50 mg of indomethacin per day. After
      informed consent was obtained, the treatment started and the absence of any
      intolerable adverse effects was confirmed in a hospital. Then the treatment
      continued in an outpatient clinic for at least 3 months. RESULTS: Of 6 assessable
      patients, 5 responded to this treatment; 2 patients developed a partial response
      (33%) and 3 remained stable (67%). Disease progressed in the remaining patient.
      Therapy was discontinued in 1 patient because of his poor general condition. No
      severe adverse effects were observed, but pulmonary fibrosis probably associated
      with this treatment occurred in 1 patient. CONCLUSION: Although more cases and
      further evaluation are necessary to assess the significance and the safety of the
      inhalation of interleukin-2, this treatment is anticipated to be an option for
      selected patients with lung metastases from renal cell carcinoma.

PMID- 9256322
TI  - Endoscopic injection of Teflon for correction of primary vesicoureteral reflux in
      children.
AB  - BACKGROUND: Treatment of vesicoureteral reflux by endoscopic injection of Teflon
      paste has recently demonstrated a good success rate. This report describes our
      experience in treating vesicoureteral reflux in children with particular
      reference to follow-up data. METHODS: Between December 1993 and November 1994,
      endoscopic injection of Teflon paste into the submucosa was performed on 18
      children (29 ureters) to correct vesicoureteral reflux. RESULTS: After treatment,
      reflux was eliminated in 75.9%, decreased in 13.8%, and unchanged in 10.3% of the
      ureters. The success rate was lower for high grade reflux cases and ureteral
      orifices with abnormal shapes. CONCLUSION: Long-term follow-up for up to 2 years
      demonstrated that although late recurrence may occur in a small proportion of
      cases, the procedure is safe, simple and effective for correcting vesicoureteral
      reflux.

PMID- 9256323
TI  - Significance of the preoperative intravesical instillation of doxorubicin and the
      oral administration of 5-fluorouracil in preventing recurrence after a
      transurethral resection of superficial bladder cancer. Kyushu University
      Urological Oncology Group.
AB  - BACKGROUND: The postoperative intravesical instillation of doxorubicin (ADM) has
      a preventative effect on recurrence after a transurethral resection (TUR) of
      superficial bladder cancer. However, the significance of preoperative ADM
      instillation remains unclear. Although the oral administration of 5-fluorouracil
      (5-FU) has been observed to show some clinical response against bladder cancer,
      its preventative effect on the recurrence of superficial bladder cancer after TUR
      is unknown. METHODS: Patients were randomized into 4 groups. All 4 groups
      received postoperative ADM instillation. In addition, patients in groups C and D
      received preoperative ADM instillation, whereas patients in groups B and D
      additionally received oral 5-FU postoperatively. The nonrecurrence rate and side
      effects were both compared among the 4 groups. RESULTS: Of the 282 patients
      registered, 200 were evaluable, with a median follow-up period of 21.4 months.
      There were no significant differences in the characteristics of the patients
      among the 4 groups. Group C (pre- and postoperative ADM) showed a significantly
      longer disease-free interval than group A (postoperative ADM alone). However,
      there was no significant difference in the disease-free interval between groups A
      and B (postoperative ADM plus 5-FU), or between groups C and D (pre- and
      postoperative ADM plus 5-FU). Bladder irritation symptoms were the most
      frequently noted side effect encountered in all groups, but the severity was
      generally mild. CONCLUSIONS: Preoperative ADM instillation was found to prevent
      recurrence to a greater extent than the usual postoperative instillation alone,
      whereas oral 5-FU was found to have no additional beneficial effect on the
      disease-free interval in patients with superficial bladder cancer.

PMID- 9256324
TI  - Influence of prostate size on terazosin efficacy.
AB  - BACKGROUND: While the rationale for the use of alpha1-adrenoreceptor antagonists
      in the treatment of bladder outlet obstruction is well established, not all
      patients have either objective or subjective improvement. The aim of this study
      was to evaluate the influence of prostatic size on the changes of peak flow rate,
      average flow rate and residual urine in symptomatic BPH patients undergoing
      terazosin treatment. METHODS: Thirty-five patients with symptomatic BPH received
      terazosin, 5 mg once a day for 3 weeks after a 2-week dose escalation period.
      Peak and average flow rates as well as residual urine were assessed before and
      after treatment. The patients were stratified in 3 groups by prostate size, which
      was estimated by transabdominal ultrasonography and a digital rectal examination.
      RESULTS: The baseline characteristics for age, peak flow rate and average flow
      rate did not vary between the 3 groups, however, the pretreatment volume of
      residual urine was greater in patients with large prostate adenomas. Terazosin
      treatment resulted in significant changes in flow rate and residual urine,
      however, changes in flow rates were not influenced by prostate size, while a
      marked decrease in residual urine was found in patients with large prostates.
      CONCLUSION: Patients treated with terazosin obtained similar improvement in peak
      and average uroflow, independent of the size of the prostate.

PMID- 9256325
TI  - Evaluation of prostate specific antigen density and transrectal ultrasonography
      guided biopsies in 100 consecutive patients with a negative digital rectal
      examination and intermediate serum prostate specific antigen levels.
AB  - BACKGROUND: This study was undertaken to assess the importance of prostate
      biopsies in patients with a negative digital rectal examination (DRE) and
      elevated prostate specific antigen (PSA) levels and to investigate the role of
      PSA density (PSAD) and hypoechoic lesions on transrectal ultrasound (TRUS) in
      increasing the diagnostic sensitivity and specificity for prostate cancer (PCa).
      METHODS: One hundred patients with varied initial symptoms who had a negative DRE
      and a PSA level between 4 and 20 ng/mL underwent TRUS-guided systematic and, if
      present, lesion-directed biopsies. RESULTS: PCa was detected in 11 patients
      (11%). TRUS examinations revealed hypoechoic lesions in 31 patients. Lesion
      directed biopsies revealed PCa in 13% (4/31) of patients with abnormal TRUS
      whereas, 7% (5/69) of patients with negative TRUS findings had PCa. Additional
      systematic biopsies detected PCa in 2 patients where lesion-directed biopsies
      were negative. None (0/19) of the lesions smaller than 0.2 mL on TRUS had PCa
      whereas, 33% (4/12) of patients with lesions greater than 0.2 mL had PCa. When
      the subgroup of patients with negative TRUS and PSA levels between 4 and 10 ng/mL
      were considered, 25% (1/4) of cases with PCa would have been missed if 0.15 was
      used as the cut-off point for PSAD, however, this would save 61% (30/49) of
      unnecessary biopsies. The positive predictive value of PSA (cut-off level 10
      ng/mL), PSAD (cut-off level 0.15), and hypoechoic lesions on TRUS were found to
      be 11.5%, 33%, and 13%, respectively. When hypoechoic lesions greater than 0.2 mL
      were taken as the positive finding, the positive predictive value and specificity
      rates of TRUS increased to 33% and 91%, respectively, without any change in the
      sensitivity. CONCLUSIONS: In patients with a negative DRE and intermediate PSA
      levels, the application of PSAD would have saved 49% of study patients with BPH
      from a biopsy, but would have missed 27% of PCa cases. By ignoring lesions
      smaller than 0.2 mL on TRUS, a very high specificity of 91% was achieved with a
      sensitivity of 36%. Thus, further investigations aimed at defining a better mode
      of diagnosis of PCa are warranted.

PMID- 9256326
TI  - Bone-turnover metabolites as clinical markers of bone metastasis in patients with
      prostatic carcinoma.
AB  - BACKGROUND: Candidate markers of prostatic metastases to bone, urinary
      deoxypyridinoline, serum carboxy-terminal propeptide of type 1 procollagen
      (P1CP), and pyridinoline cross-linked carboxy-terminal telopeptide of type 1
      collagen (1CTP), were measured to evaluate their prognostic efficacy. METHODS:
      Urinary levels (mean +/- SD) of deoxypyridinoline were measured by a competitive
      immunoassay, and serum levels of P1CP and 1CTP were measured by radioimmunoassay
      in 30 patients with benign prostatic hyperplasia, 18 patients with prostatic
      carcinoma without bone metastases, and 27 patients with prostatic carcinoma and
      bone metastases. RESULTS: Urinary concentrations of deoxypyridinoline
      (pmol/micromol creatinine) in patients with prostatic carcinoma and bone
      metastases (10.4 +/- 7.7) were significantly higher than those in similar
      patients without bone metastases (4.3 +/- 1.3) and those in patients with benign
      prostatic hyperplasia (3.8 +/- 1.2). Serum levels of P1CP and 1CTP (ng/mL) in
      patients with prostatic carcinoma and bone metastases (262.6 +/- 188.7 and 10.3
      +/- 9.5, respectively) were significantly higher than those in similar patients
      without bone metastases (118.1 +/- 30.2 and 4.3 +/- 1.4, respectively) and those
      in patients with benign prostatic hyperplasia (93.9 +/- 25.1 and 3.3 +/- 1.1,
      respectively). Serial measurements of urinary deoxypyridinoline and serum P1CP
      and 1CTP were correlated with a positive response to treatment (reduced
      measurements) and with the clinical progression of disease (increased
      measurements) before detection of new bone lesions by bone scintigram.
      CONCLUSION: Urinary deoxypyridinoline, serum P1CP, and serum 1CTP should be
      useful markers in confirming and monitoring prostatic carcinoma metastases to
      bone.

PMID- 9256327
TI  - Detection of circulating tumor cells in patients with prostate cancer using
      prostate specific membrane-derived primers in the polymerase chain reaction.
AB  - BACKGROUND: Prostate specific membrane antigen (PSM) is a transmembrane
      glycoprotein that has been described as human prostate specific. It is possible
      that PSM could be used as a biomarker for staging prostate cancer. METHODS:
      Peripheral blood mononuclear cells from 2 groups of patients with prostate cancer
      were used for the detection of PSM messenger ribonucleic acid (mRNA) using the
      reverse transcriptase-polymerase chain reaction (RT PCR) method. Group 1
      consisted of 29 untreated patients (13 stage B cancer, 5 stage C, and 11 stage D
      cancers). Group 2 consisted of 40 treated patients (23 responded well and 17 had
      recurrence after treatment). In addition, blood specimens from 30 patients with
      benign prostatic hyperplasia, 5 women, and 5 men undergoing cystoprostatectomy
      for invasive bladder cancer were used as controls. We then correlated patient and
      disease characteristics with PCR assay results. RESULTS: Samples of all 40
      controls were negative for PSM-mRNA. Thirteen of 29 patients of group 1 (45%)
      were positive for PSM-mRNA. The PCR positive rate did not correlate with clinical
      stage, pathologic stage, tumor grade, or serum PSA levels. Nine of 40 patients
      (22%) in group 2 were positive for PSM-mRNA, and the majority (8 of 9) were
      derived from the group of patients with recurrent disease. CONCLUSIONS: A nested
      RT PCR assay for PSM mRNA can detect circulating tumor cells in the peripheral
      blood of patients with prostatic cancer. These results suggest that the detection
      of circulating tumor cells could be useful for monitoring disease progression of
      prostatic cancer.

PMID- 9256328
TI  - Activity of keratinocyte growth factor-like substance extracted from rabbit liver
      on renal tubular cell growth during compensatory renal hyperplasia.
AB  - BACKGROUND: In response to unilateral nephrectomy, the rabbit liver transiently
      produces 2 growth regulators for cultured renal cortical tubular cells: a tubular
      cell growth factor and a growth inhibitor. We report on the effects of the
      tubular cell growth factor on a variety of cell lines. METHODS: The tubular cell
      growth factor activity was partially purified from the rabbit liver by using gel
      filtration and ion-exchange chromatography. The activity was monitored by the
      incorporation of iododeoxyuridine into DNA of cultured cells. Expression of the
      fibroblast growth factor receptor-2 in the rabbit kidney was determined by the
      immunoblot analysis. RESULTS: This growth factor stimulated the DNA synthesis in
      LLC-PK1 cells, LLC-RK1 cells, and human keratinocytes. It did not affect the
      growth of BS-C-1 cells, MDCK cells, BALB/c 3T3 fibroblasts, or rat parenchymal
      hepatocytes. The additive effect of this factor on the DNA synthesis of cultured
      tubular cells maximally was stimulated by insulin-like growth factor-I, basic
      fibroblast growth factor, and epidermal growth factor, but was not stimulated by
      keratinocyte growth factor. The amount of this activity also increased in the
      liver after sham operation. In the days after surgery, expression of fibroblast
      growth factor receptor-2, which includes the keratinocyte growth factor receptor,
      was down-regulated in the kidneys of both uninephrectomized and sham-operated
      rabbits. CONCLUSION: These findings indicate that tubular cell growth factor in
      the liver seems to be a keratinocyte growth factor, and acts in an endocrine
      manner in renal tubular hyperplasia.

PMID- 9256329
TI  - Role of platelet-activating factor in two-kidney, one-clip hypertension.
AB  - BACKGROUND: Platelet-activating factor (PAF) is a bioactive phospholipid which is
      a potent hypotensive agent. To investigate the role of PAF in renovascular
      hypertension, we determined the PAF concentration and its production level
      assessed by the activity of cholinephosphotransferase (CPT) in renal tissue and
      examined the effect of a PAF antagonist on the mean arterial pressure (MAP) in
      control and two-kidney with one clipped (2K1C) hypertensive rats. MATERIALS AND
      METHODS: The concentration of PAF and CPT in the renal medulla and cortex were
      determined by radioassay. Also, the effect of a PAF antagonist, CV-6209, on MAP
      was also examined in both 2K1C hypertensive and normal control rats. RESULTS: The
      PAF concentration and CPT activity were significantly higher in the medulla than
      in the cortex in both 2K1C hypertensive and normal control rats, and both values
      in the medulla were also significantly higher in the clipped kidney than in the
      contralateral unclipped kidney or in control rat kidneys. We also observed a
      significant negative correlation between the PAF concentration in the medulla,
      and the medulla weight in the clipped kidney of 2K1C hypertensive rats. Infusion
      of the PAF antagonist, CV-6209, did not affect MAP in 2K1C hypertensive rats, but
      was significantly increased (P < 0.05) in control rats. CONCLUSIONS: These
      findings suggest that PAF, whose production is induced by renal ischemia due to
      renal artery stenosis, plays an important role in the renomedullary vasodepressor
      system, but the effect of PAF as a vasodilator in the peripheral vessels is
      limited in 2K1C hypertension.

PMID- 9256330
TI  - Urinary bladder response to hypogastric nerve stimulation after bilateral
      resection of the pelvic nerve or spinal cord injury in rats.
AB  - BACKGROUND: We examined the mechanism of urinary bladder motility return after
      bladder areflexia induced by interruption of the sacral parasympathetic outflow
      to the urinary bladder following damage to the sacral cord or pelvic nerves in
      the rat. METHODS: The L6 and S1 nerve bundles were resected near the vertebrae,
      and bilateral pelvic nerve resections (PNR) performed. Spinal cord injury (SCI)
      was performed by means of a legion generator at the T12 vertebra. Thirty days
      after PNR and SCI, cystometrograms were recorded under anesthesia. RESULTS: In
      all rats subjected to PNR or SCI, overflow incontinence continued, yet some rats
      subjected to SCI recovered within 2 weeks after the operation. Cystometrograms
      showed that repetitive bladder contractions appeared in rats subjected to SCI
      irrespective of hypogastric nerve (HGN) innervation, while bladder contractions
      did not appear in rats subjected to PNR. Electrical stimulation of the HGN
      induced higher bladder pressure elevation in rats who underwent PNR than in rats
      subjected to SCI. CONCLUSIONS: These results suggest that the generation of
      repetitive bladder contractions induced by bladder distention after bladder
      areflexia requires the presence of intact pelvic nerves that transmit sacral cord
      originating excitatory information to the bladder. However, the HGN system and
      functioning pelvic nerve ganglia are not involved in this process. Also, the
      connection from the preganglionic HGN to the postganglionic parasympathetic
      nerves in the pelvic plexus did not form after PNR.

PMID- 9256331
TI  - Effect of NS-21, an anticholinergic drug with calcium antagonistic activity, on
      lower urinary tract function in a rat model of urinary frequency.
AB  - BACKGROUND: NS-21 is under development for the treatment of urinary frequency and
      urinary incontinence. The purpose of this study was to investigate the effects of
      NS-21 and its active metabolite, RCC-36, on lower urinary tract function in an
      experimental rat model of urinary frequency. METHODS: Cystometrograms were
      recorded in anesthetized rats with bilaterally transected hypogastric nerves. All
      drugs were administered intraduodenally. RESULTS: In sham-operated rats, NS-21 (>
      or = 50 mg/kg) significantly increased the bladder capacity without significantly
      decreasing micturition pressure, while RCC-36 (100 mg/kg) significantly increased
      bladder capacity, and at a dose of > or = 30 mg/kg, also caused a decrease in
      micturition pressure. This increase in bladder capacity appeared at lower doses
      of both NS-21 and RCC-36 in the hypogastric nerve-transected rats. Propiverine
      (100 mg/kg) increased bladder capacity and at > or = 30 mg/kg, decreased
      micturition pressure in both sham-operated and nerve-transected rats. Oxybutynin
      (100 mg/kg) and atropine (30 mg/kg) decreased the micturition pressure in both
      sham-operated and nerve-transected rats without increasing the bladder capacity,
      while a similar anticholinergic calcium antagonist, terodiline (100 mg/kg) had no
      effect on bladder capacity in either sham-operated or nerve-transected rats.
      Flavoxate (500 mg/kg) significantly increased bladder capacity without
      significantly decreasing micturition pressure in both sham-operated and nerve
      transected rats, while 50 mg/kg of verapamil significantly increased bladder
      capacity without significantly decreasing the micturition pressure in nerve
      transected rats. CONCLUSIONS: NS-21 and RCC-36 increased bladder capacity at
      lower doses in hypogastric nerve-transected rats than in sham-operated rats.
      Furthermore, NS-21 increased the bladder capacity without suppressing micturition
      pressure, suggesting that NS-21 may be a more effective therapeutic drug than
      propiverine, oxybutynin or flavoxate for the treatment of urinary frequency and
      urinary incontinence.

PMID- 9256332
TI  - Telomere length and telomerase activity in bladder and prostate cancer cell
      lines.
AB  - BACKGROUND: Specific repeats of oligonucleotides at the ends of chromosomes
      (telomeres) are shortened by cell division in somatic cells and are thought to be
      related to aging. Immortal cells such as germ-line cells or cancer cells have
      demonstrated increased activity of the telomere-elongating enzyme (telomerase).
      The length of the telomeres of these cells is stable regardless of cell division.
      We examined the telomere length and telomerase activity in 3 bladder (JTC30,
      JTC32, and T24) and 2 prostate cancer (LNCaP and DU145) cell lines. METHODS:
      Telomere lengths were evaluated by Southern blot analysis with a oligonucleotide
      probe, (TTAGGG)5, and telomerase activities were detected with a polymerase chain
      reaction-based assay method. RESULTS: Telomerase activity was detected in all of
      the cell lines. Each cell line had a specific telomere length. In 2 bladder
      cancer cell lines (JTC30 and JTC32), the telomere length decreased with increased
      passage of the cells. CONCLUSION: The presence of telomerase may be a biological
      character of bladder and prostate cancers as well as other malignancies, although
      it does not always compensate telomere shortening.

PMID- 9256333
TI  - Potentiating effect of buserelin acetate, an LHRH agonist, on the proliferation
      of ventral prostatic epithelial cells in testosterone-treated castrated rats.
AB  - BACKGROUND: We used buserelin acetate ([D-Ser(But)6] LHRH ), an LHRH agonist and
      strong blocker of LH secretion, as a treatment for prostatic cancer. It is
      possible that this LHRH agonist has a proliferative effect on the prostate in
      addition to suppressing LH secretion. The purpose of this study was to examine
      the proliferative effect of LHRH agonist on rat prostatic epithelial cells.
      METHODS: We determined the optimal dose of testosterone necessary to maintain a
      positive level of proliferating cell nuclear antigen (PCNA) in the ventral
      prostatic epithelial cells of castrated Wistar rats. Testosterone-treated rats
      then received various doses of buserelin acetate. Castrated rats without
      exogenous testosterone also received buserelin acetate. The PCNA positivity was
      determined by immunohistochemistry with anti-PCNA monoclonal antibody. RESULTS:
      The optimal dose of testosterone enanthate was 4 mg at 0 and 28 days after
      castration. Administration of buserelin acetate on day 0 and 28 in doses of 0.16
      mg to 1.28 mg significantly increased PCNA positivity in a dose-dependent manner.
      Administration of buserelin acetate to castrated rats without testosterone also
      increased PCNA positivity but there was no statistical significance. CONCLUSIONS:
      Buserelin acetate has a potentiating effect on the proliferation of ventral
      prostatic epithelial cells of castrated rat in the presence of a physiological
      level of exogenous testosterone. This effect may slightly influence the result of
      hormonal therapy by LHRH agonist.

PMID- 9256334
TI  - Incorrect positioning of an indwelling urethral catheter in the ureter.
AB  - An unusual case where a urethral catheter was indwelt in the left ureter is
      presented. A small contracted bladder and a patulous ureteral orifice appeared to
      be causative factors of this complication.

PMID- 9256335
TI  - Extracorporeal shock wave lithotripsy-induced renal laceration.
AB  - After extracorporeal shock wave lithotripsy (ESWL), perinephric hematomas, while
      uncommon, are a serious complication involving the risk of blood transfusion and
      subsequent impairment of renal function. We report a rare case of ESWL-induced
      renal laceration in which an expanding retroperitoneal hematoma required blood
      transfusion but was treated successfully without surgical intervention.

PMID- 9256337
TI  - Ex vivo partial nephrectomy and partial kidney autotransplantation for renal
      pelvic carcinoma in a functionally solitary kidney: case report.
AB  - A 46-year-old Japanese man was diagnosed with a left renal pelvic carcinoma and a
      contralateral hypoplastic kidney. The tumor was adjacent to the renal pelvis and
      was considered too difficult to completely resect in situ. The patient was
      treated by ex vivo partial nephrectomy of the left kidney followed by
      autotransplantation of the remaining renal segment. A pathologic evaluation
      revealed a transitional cell carcinoma, G2, pT3. Graft function recovered
      satisfactorily postautotransplantation and no significant complications developed
      during the postoperative period. The patient is alive and doing well 12 months
      postoperatively with no evidence of tumor recurrence.

PMID- 9256336
TI  - Small cell carcinoma of the kidney: case report.
AB  - An 83-year-old female diagnosed with small cell carcinoma of the kidney is
      reported on. The clinical picture was similar to that seen with transitional cell
      carcinoma of the renal pelvis. A right nephroureterectomy was performed and a
      histological examination revealed similar morphological features to those of
      small cell carcinoma of the lung. Neuroendocrine differentiation was proven by a
      positive immunoreaction to neuron-specific enolase. A review of the literature
      indicated that in the urinary tract, most of the cases of small cell carcinoma
      occurred in the urinary bladder, with this case being the eleventh reported case
      of small cell carcinoma originating in the kidney. As with many of the other
      cases of small cell carcinoma of the urinary tract, this patient's tumor was
      associated with both adenomatous and squamous differentiation. The patient died 2
      months after surgery, prior to any chemotherapy administration.

PMID- 9256338
TI  - Incontinent ileal tube repaired by infolding with the ileal pouch wall.
AB  - In a patient who had undergone construction of a continent ileal pouch we
      successfully repaired an incontinent ileal tube by infolding it in an imbricated
      portion of the ileal pouch wall. For 2 years postoperatively the patient has been
      urine continent and has catheterized the pouch easily. We believe this infolding
      technique is useful for reconstructing the continent mechanism in patients with
      incompetent ileal valves.

PMID- 9256340
TI  - Characteristics of clinical medicine.

PMID- 9256339
TI  - Distal penile gangrene in a patient with chronic renal failure.
AB  - To date, only 10 cases of distal penile gangrene in patients with chronic renal
      failure have been reported. This rare condition is believed to result from
      progressive vascular calcification due to secondary hyperparathyroidism in
      patients with chronic renal failure. We report an additional case of distal
      penile gangrene in a 41-year-old man who presented with chronic renal disease and
      pulmonary tuberculosis. Since some authors have emphasized that aggressive
      surgical treatment in such cases has a significant mortality rate, we took a more
      conservative approach to treatment.

PMID- 9256341
TI  - Miz1, a novel zinc finger transcription factor that interacts with Msx2 and
      enhances its affinity for DNA.
AB  - Msx2 is a homeobox gene with a regulatory role in inductive tissue interactions,
      including those that pattern the skull. We demonstrated previously that
      individuals affected with an autosomal dominant disorder of skull morphogenesis
      (craniosynostosis, Boston type) bear a mutated form of Msx2 in which a histidine
      is substituted for a highly conserved proline in position 7 of the N-terminal arm
      of the homeodomain (p148h). The mutation behaves as a dominant positive in
      transgenic mice. The location of the mutation in the N-terminal arm of the
      homeodomain, a region which in other homeodomain proteins plays a key part in
      protein-protein interactions, prompted us to undertake a yeast two hybrid screen
      for Msx2-interacting proteins. Here we present a functional analysis of one such
      protein, designated Miz1 (Msx-interacting-zinc finger). Miz1 is a zinc finger
      containing protein whose amino acid sequence closely resembles that of the yeast
      protein, Nfi-1. Together these proteins define a new, highly conserved protein
      family. Analysis of Miz1 expression by Northern blot and in situ hybridization
      revealed a spatiotemporal pattern that overlaps that of Msx2. Further, Miz1 is a
      sequence specific DNA binding protein, and it can function as a positive-acting
      transcription factor. Miz1 interacts directly with Msx2 in vitro and enhances the
      DNA binding affinity of Msx2 for a functionally important element in the rat
      osteocalcin promoter. The p148h mutation in Msx2 augments the Miz1 effect on Msx2
      DNA binding, suggesting a reason why this mutation behaves in vivo as a dominant
      positive, and providing a potential explanation of the craniosynostosis
      phenotype.

PMID- 9256342
TI  - Differential accumulation of DPTP61F alternative transcripts: regulation of a
      protein tyrosine phosphatase by segmentation genes.
AB  - DPTP61F is a non-receptor protein tyrosine phosphatase that is expressed during
      Drosophila oogenesis and embryogenesis. DPTP61F transcripts are alternatively
      spliced to produce two isoforms of the protein which are targeted to different
      subcellular locations. DPTP61Fn accumulates in the nucleus, and DPTP61Fm
      associates with the membranes of the reticular network and the mitochondria. We
      have examined the spatial and temporal expression of the two alternative
      transcripts of dptp61F during Drosophila embryogenesis. Our observations indicate
      that the two isoforms are expressed in distinct patterns. The DPTP61Fn transcript
      is expressed in the mesoderm and neuroblast layer during germband extension and
      later in the gut epithelia. In comparison, the transcript encoding DPTP61Fm
      accumulates in 16 segmentally repeated stripes in the ectoderm during germband
      extension. These stripes are flanked by, and adjacent to, the domains of
      engrailed and wingless gene expression in the anterior/posterior axis. In stage
      10 embryos, the domains of DPTP61Fm transcript accumulation are wedge shaped and
      roughly coincide with the area lateral to the denticle belts that will give rise
      to naked cuticle. The DPTP61Fm transcript is also expressed later in
      embryogenesis in the central nervous system. The segmental modulation of DPTP61Fm
      transcript accumulation in the A/P axis of the germband is regulated by the pair
      rule genes, and the intrasegmental pattern of transcript accumulation is
      regulated by the segment polarity genes.

PMID- 9256343
TI  - Krox-20 is a key regulator of rhombomere-specific gene expression in the
      developing hindbrain.
AB  - The morphogenesis of the vertebrate hindbrain involves a transient segmentation
      process leading to the formation of reiterated organisation units called
      rhombomeres (r). A number of regulatory genes expressed with a rhombomere
      specific pattern have been identified, including the gene encoding the
      transcription factor Krox-20, which is restricted to r3 and r5. We have
      previously demonstrated that in r3 and r5 Krox-20 directly controls the
      transcription of Hoxa-2 and Hoxb-2. In the present study, we provide evidence
      that Krox-20 is required for the expression of another Hox gene, Hoxb-3, in r5
      specifically. Furthermore, the regulatory role of Krox-20 is not restricted to
      the control of Hox gene expression, since it is also involved in the activation
      of a receptor tyrosine kinase gene, Sek-1, in r3 and r5 and in the repression of
      the follistatin gene in r3 but not in r5. In conclusion, at least five regulatory
      genes belonging to different families are under the direct or indirect control of
      Krox-20 in r3 and/or r5 and this transcription factor therefore appears as a key
      regulator of gene expression in the developing hindbrain.

PMID- 9256344
TI  - Induction of yolk sac endoderm in GATA-4-deficient embryoid bodies by retinoic
      acid.
AB  - GATA-4, a transcription factor implicated in lineage determination, is expressed
      in both parietal and visceral endoderm of the early mouse embryo. In embryonic
      stem cell-derived embryoid bodies, GATA-4 mRNA is first detectable at 4-5 days of
      differentiation and is confined to visceral endoderm cells on the surface of the
      bodies. Previously we reported that targeted mutagenesis of the Gata4 gene in
      embryonic stem cells results in a block in visceral endoderm differentiation in
      vitro. In an attempt to elucidate the role of GATA-4 in the formation of visceral
      endoderm, we have now differentiated Gata4 -/- and wild type embryoid bodies in
      the presence of retinoic acid +/- dbcAMP, known inducers of endoderm formation.
      We show that differentiation of Gata4 -/- embryoid bodies in the presence of
      retinoic acid results in formation of visceral endoderm, while differentiation of
      Gata4 -/- embryoid bodies in the presence of retinoic acid plus dbcAMP causes
      parietal endoderm formation. The presence of these yolk sac endoderm layers was
      confirmed by light microscopy and analysis of biochemical markers including alpha
      fetoprotein, type IV collagen, laminin, and binding sites for Dolichos biflorus
      agglutinin. Treatment of Gata4 -/- embryoid bodies with retinoic acid induces
      expression of another GATA-binding protein, GATA-6, in both visceral and parietal
      endoderm cells. That another GATA-binding protein is induced in the absence of
      GATA-4 suggests that this family of transcription factors plays an important role
      in yolk sac differentiation.

PMID- 9256345
TI  - The Evi1 proto-oncogene is required at midgestation for neural, heart, and
      paraxial mesenchyme development.
AB  - The ecotropic viral integration site-1 (Evi1) locus was initially identified as a
      common site of retroviral integration in myeloid tumors of the AKXD-23
      recombinant inbred mouse strain. The full-length Evi1 transcript encodes a
      putative transcription factor, containing ten zinc finger motifs found within two
      domains of the protein. To determine the biological function of the Evi1 proto
      oncogene, the full-length, but not an alternately spliced, transcript was
      disrupted using targeted mutagenesis in embryonic stem cells. Evi1 homozygous
      mutant embryos die at approximately 10.5 days post coitum. Mutants were
      distinguished at 10.5 days post coitum by widespread hypocellularity,
      hemorrhaging, and disruption in the development of paraxial mesenchyme. In
      addition, defects in the heart, somites, and cranial ganglia were detected and
      the peripheral nervous system failed to develop. These results correlated with
      whole-mount in situ hybridization analyses of embryos which showed expression of
      the Evi1 proto-oncogene in embryonic mesoderm and neural crest-derived cells
      associated with the peripheral nervous system. These data suggest that Evi1 has
      important roles in general cell proliferation, vascularization, and cell-specific
      developmental signaling, at midgestation.

PMID- 9256346
TI  - Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during
      mouse development.
AB  - We studied the expression of the estrogen-related receptor 1 (ERR-1) during mouse
      embryonic development. ERR-1 is expressed at very early stages in ES cells and at
      E8.5 in the mesodermal cells of the visceral yolk sac. ERR-1 continues to be
      expressed later in mesodermal tissues and particularly in heart and in skeletal
      muscles. This expression persists during all the embryonic development and in
      adult stage. ERR-1 transcripts level increases during muscle differentiation.
      Accordingly, we show that ERR-1 expression increases during the myoblast to
      myotube transition in differentiating C2 myoblastic cells. ERR-1 has also been
      detected in the nervous system during embryonic development. At E10.5, a high
      level of ERR-1 transcripts can be observed in differentiated cells of the
      intermediate zone of the spinal cord which also suggests a role of ERR-1 in the
      differentiation of the nervous system. The same is observed in the telencephalon
      vesicules at E13.5. Later, at E15.5 and E17.5, expression persists in the spinal
      cord but decreases dramatically in the central nervous system. Moreover, ERR-1
      expression increases during skin formation and is detected in the stratum
      spinosum which contains differentiated Malpighian cells. Finally, we also
      observed ERR-1 in endodermal derivatives such as the epithelium of intestine and
      urogenital system. The DNA target of ERR-1 has been identified to be the SF-1/FTZ
      F1 responsive element (SFRE) and we show in this paper that SF-1/FTZ-F1 and ERR-1
      bind to and activate transcription independently through the SFRE element. Our
      study suggests that ERR-1 may be implicated in numerous physiological or
      developmental functions, particularly in the muscle, the central and peripheral
      nervous system and the epidermis. Interestingly, in these various systems ERR-1
      expression is correlated with post-mitotic cells stage, suggesting that ERR-1 may
      play a role in the differentiation process.

PMID- 9256347
TI  - Spx1, a novel X-linked homeobox gene expressed during spermatogenesis.
AB  - Spx1, a novel mouse homeobox gene, encodes a homeodomain characteristic of the
      paired-like class of homeobox genes and has been mapped to the distal end of the
      X chromosome. Northern blot hybridization of adult tissues detected high levels
      of a single Spx1 transcript in the testis. Further analysis by in situ
      hybridization revealed predominant Spx1 expression within the
      spermatogonia/preleptotene spermatocytes and round spermatids of spermatogenic
      stages IV-VII. These expression data suggest SPX1 may play a role in the
      regulation of spermatogenesis.

PMID- 9256348
TI  - Expression of a novel aristaless related homeobox gene 'Arx' in the vertebrate
      telencephalon, diencephalon and floor plate.
AB  - We have isolated a novel homeobox gene that is expressed in the vertebrate
      central nervous system and which shows striking similarity to the Drosophila al
      gene in the homeodomain (85% identity) and in a 17 amino acid-sequence near the
      carboxyl-terminus. This gene was designated Arx (aristaless related homeobox
      gene) in consideration of its structural similarity to the al gene. Arx was
      highly conserved between mouse and zebrafish. Neuromeric expression in the
      forebrain and longitudinal expression in the floor plate were observed in mouse
      and zebrafish. The expression of Arx in the ganglionic eminence and ventral
      thalamus overlapped regionally with that of Dlx1, but the cell layer where Arx is
      expressed differed from that of the Dlx1. This gene was also found to be
      expressed in the dorsal telencephalon (presumptive cerebral cortex) of mouse
      embryos. The structure and expression pattern of Arx with respect to any possible
      relationship to al and Dlx1, as well as the function of Arx in the floor plate
      are discussed.

PMID- 9256349
TI  - The expression pattern of the mafB/kr gene in birds and mice reveals that the
      kreisler phenotype does not represent a null mutant.
AB  - The recessive mouse mutation kreisler affects hindbrain segmentation and inner
      ear development in homozygous mice. The mouse gene affected by the mutation was
      found to encode a basic domain leucine-zipper (bZIP)-type transcription factor of
      the Maf-family named kr (Cordes, S.P. and Barsh, G.S. (1994) Cell 79, 1025-1034).
      The avian bZIP transcription factor mafB, which shows high homology to kr, has
      been identified as an interaction partner of c-Ets 1 (Sieweke, M.H., Tekotte,
      M.H., Frampton, J. and Graf, T. (1996) Cell 85, 49-60). Here we demonstrate by
      Southern blot analysis that mafB is the avian homologue of kr, and present a
      detailed pattern of its expression during avian and murine embryonic development.
      Consistent with the kreisler phenotype, mafB is expressed in avians in the
      tissues which are affected by the mouse mutation: rhombomeres 5 and 6 (r5 and r6)
      and the neural crest derived from these rhombomeres. However, our analysis
      reveals a variety of additional expression sites: mafB/kr expression persists in
      vestibular and acoustic nuclei and is also observed in differentiating neurons of
      the spinal cord and brain stem. Restricted expression sites are found in the
      mesonephros, the perichondrium, and in the hemopoietic system. Since these
      expression sites are conserved between mouse and chicken we reexamined homozygous
      kreisler mice for unrevealed phenotypes in the hemopoietic system. However,
      peritoneal macrophages from homozygous kreisler mice were found to be
      functionally normal and still expressed mafB/kr. Other adult tissues examined
      from homozygous kreisler mice had also not lost mafB/kr expression. Our results
      thus indicate that the kreisler mutation involves a tissue specific gene
      inactivation and suggest additional roles for mafB/kr in later developmental and
      differentiation processes that are not revealed by the mutation.

PMID- 9256350
TI  - Insertional mutation of the mouse Msx1 homeobox gene by an nlacZ reporter gene.
AB  - We have generated a null allele of the mouse Msx1 homeobox gene by insertion of
      an nlacZ reporter gene into its homeobox. The sensitivity of beta-galactosidase
      detection permitted us to reveal novel aspects of Msx1 gene expression in
      heterozygous embryos, in particular in ectoderm and mesoderm during gastrulation,
      and in migrating neural crest cells. Homozygous mutant mice die at birth with
      facial defects (see Satokata, I. and Maas, R. (1994) Msx1 deficient mice exhibit
      cleft palate and abnormalities of craniofacial and tooth development. Nat. Genet.
      6, 348-356). To investigate the reason for this limited phenotype, we compared
      the pattern of Msx1 expression with that of the closely related Msx2 gene in wild
      type embryos and in Msx1-/- mutants. Notably, whereas the expression of Msx1 and
      Msx2 overlap in the developing limb, this is not the case in the facial regions
      most affected in the mutant.

PMID- 9256351
TI  - Assembly of the zygotic centrosome in the fertilized Drosophila egg.
AB  - Zygotic centrosome assembly in fertilized Drosophila eggs was analyzed with the
      aid of an antiserum Rb188, previously shown to be specific for CP190, a 190 kDa
      centrosome-associated protein (Whitfield et al. (1988) J. Cell Sci. 89, 467-480;
      Whitfield et al. (1995) J. Cell Sci. 108, 3377-3387). The CP190 protein was
      detected in two discrete spots, associated with the anterior and posterior ends
      of the elongating nucleus of Drosophila spermatids. As the spermatids matured,
      this labelling gradually disappeared and was no longer visible in sperm dissected
      from spermathecae and ventral receptacles. gamma-Tubulin was also found in
      association with the posterior end of the sperm nucleus during spermiogenesis,
      but was not detected in mature sperm. This suggests that CP190 and gamma-tubulin
      are not present in detectable quantities in fertilizing sperm. CP190 was not
      detected in association with the sperm nucleus of newly fertilized eggs removed
      from the uterus, whereas many CP190-positive particles were associated with
      microtubules of the sperm aster from anaphase I to anaphase II. These particles
      disappeared during early telophase II and only one pair of CP190-positive spots
      remained visible at the microtubule focus of the sperm aster. These spots were
      associated with one aster through telophase, and then moved away to form two
      smaller asters from which the first mitotic spindle was organized. Colchicine
      treatment suggested that at least some CP190 protein is an integral part of the
      centrosome rather than merely being transported along microtubules. Centrosomal
      localization of the CP190 antigen was prevented by incubation of the
      permeabilized zygote in 20 mM EDTA.

PMID- 9256352
TI  - Bapx1: an evolutionary conserved homologue of the Drosophila bagpipe homeobox
      gene is expressed in splanchnic mesoderm and the embryonic skeleton.
AB  - In Drosophila, the visceral mesoderm giving rise to gut musculature is specified
      by the bagpipe homeobox gene. We have isolated, from both mouse and human,
      homologues of the bagpipe gene designated Bapx1 and BAPX1, respectively. Bapx1
      encodes a predicted protein of 333 amino acids, and has significant regions of
      homology outside the homeodomain with members of the NK homeobox gene
      superfamily. Bapx1 maps to the proximal end of chromosome 5 in mouse, near the
      Msx1 gene. The syntenic region in human corresponds to a chromosomal region
      containing loci for several skeletal disorders. Bapx1 is first detectable in
      embryos just prior to axis rotation in lateral plate mesoderm (splanchnic
      mesoderm) adjacent to the endodermal lining of the prospective gut, and in the
      most newly formed somites in the region corresponding to the presclerotome, the
      precursor of the vertebrae. Thus, Bapx1 is one of the earliest developmental
      markers for the sclerotome portion of the somite and the gut mesentery. Bapx1
      continues to be expressed well into organogenesis in lateral plate mesoderm
      surrounding the mid- and hindgut, and in essentially all cartilaginous
      condensations which will subsequently undergo endochondral bone formation. The
      expression pattern of Bapx1 in murine embryos suggests that there are
      evolutionary conserved mechanisms of visceral mesoderm development across the
      animal kingdom, and that the mammalian Bapx1 gene may have recently acquired an
      additional developmental role in skeletal patterning.

PMID- 9256353
TI  - Expression of contact, a new zebrafish DVR member, marks mesenchymal cell
      lineages in the developing pectoral fins and head and is regulated by retinoic
      acid.
AB  - Contact, a new zebrafish transforming growth factor-beta (TGF-beta) member is
      most closely related to mouse GDF5 and to human CDMP-1 responsible, when mutated,
      for limb brachypodism phenotype and Hunter-Thompson syndrome, respectively.
      Contact exhibits a dynamic spatial expression pattern in the pharyngeal arches
      and the pectoral fin buds that much prefigures cartilage formation. Within the
      fin buds, contact expression is detected in the proximal mesenchyme from which
      the endoskeleton will develop. Exogeneously applied retinoic acid (RA) induces
      duplication of the pectoral fin rudiment in zebrafish embryos as well as contact
      expression along the proximal margin of the fin mesenchyme showing that both
      endoskeleton and exoskeleton can be duplicated.

PMID- 9256354
TI  - A zebrafish Id homologue and its pattern of expression during embryogenesis.
AB  - We describe the cloning, sequencing and pattern of transcript distribution during
      embryogenesis of a zebrafish Id homologue that we have called Id6. Transcription
      of the gene is spatially regulated, and its pattern of transcription shows
      considerable overlaps with those of other zebrafish genes with homology to
      Drosophila neurogenic genes, such as Notch and Delta. Since all these genes are
      coexpressed in particular cells, they may function together in a single genetic
      circuit in zebrafish as they do in Drosophila. A zebrafish homologue of
      Drosophila AS-C proteins can activate transcription of a CAT reporter gene by
      binding to an E-box in mouse 3T3 cells, either alone or in conjunction with
      ZfE12. The activation of transcription is inhibited in the presence of Id6. This
      indicates that the zebrafish gene described here is a genuine member of the Id
      family, and suggests that it may serve a function similar to that of the
      Drosophila gene emc and mammalian Ids during development.

PMID- 9256355
TI  - Interaction of goosecoid and brachyury in Xenopus mesoderm patterning.
AB  - Detailed in situ analyses reveal overlapping expression of gsc and Xbra in the
      early Spemann's organizer. Coexpression is lost during gastrulation suggesting an
      interaction between these genes. Ectopic expression of gsc ventrally suppresses
      endogenous Xbra expression and transcription from Xbra promoter reporter gene
      constructs. Suppression is mediated, at least partially, by a gsc-binding site
      within the first 349 bp of the promoter. Xbra reporter gene transcription is also
      suppressed in the region of endogenous gsc expression, whereas high-level ectopic
      Xbra expression has no effect on endogenous gsc expression. We suggest that early
      patterning of the vertebrate mesoderm, like early patterning of the Drosophila
      embryo, occurs by first establishing broad domains of gene expression which are
      subsequently refined by intergenic interactions to further delimit tissue
      boundaries.

PMID- 9256356
TI  - The Drosophila bunched gene is a homologue of the growth factor stimulated
      mammalian TSC-22 sequence and is required during oogenesis.
AB  - A Drosophila melanogaster sequence homologous to the mammalian growth factor
      stimulated TSC-22 gene was isolated in an enhancer trap screen for genes
      expressed in anterodorsal follicle cells during oogenesis. This sequence includes
      a 225 aa residue open reading frame that encompasses a leucine zipper motif
      immediately preceded by a highly conserved region (TSC box), similarly located
      but distinct from the basic domain of bZIP proteins. The gene encoding this
      sequence, bunched (bun), has been independently isolated and characterized with
      respect to its role in peripheral nervous system development and eye development
      (Treisman, J.E., Lai, Z.-C. and Rubin, G.M. (1995) Shortsighted acts in the
      decapentaplegic pathway in the Drosophila eye development and has homology to a
      mouse TGF-beta-responsive gene. Development 121, 2835-2845). In agreement with
      the expression of the enhancer detector insertion, in situ hybridization reveals
      that bun transcripts localize to the anterior dorsal follicle cells at stages 10
      12 of oogenesis. Changes in bun enhancer trap expression in genetic backgrounds
      that disrupt the grk/Egfr signaling pathway suggest that bun is regulated by
      growth factor patterning of dorsal anterior follicle cell fates. Clonal analysis
      shows that bun is required for the proper elaboration of dorsal cell fates
      leading to the formation of the dorsal appendages.

PMID- 9256357
TI  - The Drosophila homeotic gene moira regulates expression of engrailed and HOM
      genes in imaginal tissues.
AB  - moira is a member of the trithorax group of homeotic gene regulators in
      Drosophila melanogaster. We show that moira is required for the function of
      multiple homeotic genes of the Antennapedia and bithorax complexes (HOM genes) in
      most imaginal tissues and that the requirement for moira function is at the level
      of transcription. moira is also required for transcription of the engrailed
      segmentation gene in the imaginal wing disc. The abnormalities caused by the loss
      of moira function in germ cells suggests that at least one other target gene
      requires moira for normal oogenesis.

PMID- 9256358
TI  - A renin-like enzyme in the leech Theromyzon tessulatum.
AB  - We report on the biochemical isolation and characterization of a 32 kDa aspartyl
      protease from the leech Theromyzon tessulatum. Following a three step
      purification (gel permeation chromatography, pepstatin A-sepharose affinity
      column separation followed by reversed-phase HPLC) a renin-like enzyme was
      purified to homogeneity. The first 124 amino acid residues of the N-terminal part
      of the purified S-pyridylethylated leech renin exhibits a 26.5-35.5% sequence
      identity with that of mammals. The 20-81 region of leech renin exhibits a 80%
      sequence homology with the 175-232 region in mammals. This highly conserved
      region, which is also found in all aspartic proteases, possesses the aspartyl
      catalytic residue (D11TGSS). Leech renin hydrolyses at neutral pH and at 37
      degrees C the Leu10-Leu11 bond of synthetic porcine angiotensinogen
      tetradecapeptide yielding the angiotensin I and the Leu11-Val12-Tyr13-Ser14
      peptides, with a specific activity of 115 microg AI/min/mg (K[M] 22 microM;
      K[cat], 2.7). This hydrolysis is inhibited by pepstatin A (IC50: 4.6 microM).
      Moreover, this enzyme is found on a multiple hormone precursor of 19 kDa which
      exhibits a specific activity of 850 pmol AI/min/mg of renin. This is the first
      biochemical characterization of a renin-like enzyme in invertebrates and non
      mammalian vertebrates.

PMID- 9256359
TI  - Vascular endothelial growth factor and its receptors in normal human testicular
      tissue.
AB  - Expression of vascular endothelial growth factor (VEGF), also known as vascular
      permeability factor (VPF), and its receptors Flt-1 and KDR (Flk-1 in mouse) and
      their localization in the human testis were analyzed by means of reverse
      transcriptase-polymerase chain reaction (RT-PCR), Western blotting and
      immunohistochemistry. VEGF mRNA was detected in the human testicular tissue and
      in fragments of seminiferous tubules by means of RT-PCR, while fragments of blood
      vessels isolated from testes were negative. Western blotting procedure using a
      specific VEGF antibody, revealed two protein bands corresponding to 24 and 49 kDa
      in the extracts prepared from the whole testis and in the seminiferous tubules
      while no such bands were found in isolated fragments of human testicular blood
      vessels. Also immunohistochemically, human testicular blood vessels show no VEGF
      immunoreactivity, while Leydig cells and Sertoli cells were positive. The mRNA of
      the VEGF receptor Flt-1 was found to be expressed in human testicular tissue, in
      isolated fragments of testicular blood vessels and in seminiferous tubules as
      determined by RT-PCR procedure. In accordance with these results, the Flt-1
      protein was immunohistochemically localized in Leydig, Sertoli and perivascular
      cells. Endothelial cells of certain segments of human testicular microvasculature
      also stained positive for Flt-1. Expression of VEGF receptor, KDR, could be
      demonstrated in human testicular tissue, in isolated seminiferous tubules and in
      isolated fragments of human testicular blood vessels by means of RT-PCR.
      Immunohistochemically, the KDR protein was localized in endothelial cells and
      perivascular cells of capillaries within the lamina propria of seminiferous
      tubules. Leydig cells and Sertoli cells show KDR immunoreactivity, too. Thus we
      demonstrate the presence of both types of VEGF receptors Flt-1 and KDR on Leydig
      as well as on Sertoli cells which are normal non-endothelial cells, suggesting
      hitherto unrecognized and novel functions for such receptors. The results
      obtained permit us to suggest VEGF as a paracrine mitogenic and angiogenic
      factor, responsible for modulating the capillarization of the human testicular
      tissue and maintaining the functions of testicular microvasculature. VEGF may
      also influence the permeability of capillaries passing through the groups of
      Leydig cells and those localized within the lamina propria of human seminiferous
      tubules. The differences in the expression pattern of the VEGF receptors in the
      human testicular tissue probably reflect different VEGF effects in different
      compartments of human testis.

PMID- 9256360
TI  - Transforming growth factor beta1 inhibits steroidogenesis in dispersed fetal
      testicular cells in culture.
AB  - TGF beta1 has been detected by immunohistochemistry in the rat fetal testis.
      Therefore, we attempted to determine whether this factor can act as a local
      regulator of Leydig cell function during fetal development. An inhibitory effect
      of TGF beta1 on basal and luteinizing hormone (LH)-stimulated testosterone
      secretion by fetal testes in vitro was observed only with testes from 13.5 day
      old fetuses and not with testes from older stages. The lack of effect of
      exogenous TGF beta1 in organ culture after day 13.5 might be related to an
      elevated intratesticular concentration that would already exert maximal
      biological effect. On the contrary, in a model of dispersed testicular cells in
      culture, TGF beta1 was able to inhibit LH-stimulated testosterone production by
      fetal Leydig cells from 16.5 and 20.5 day-old fetuses. This inhibition of LH
      stimulated testosterone production was dose- and time-dependent and was maximal
      after 48 h of treatment with 1 ng/ml TGF beta1, with testosterone secretion being
      reduced to 25% of control values. Inhibition of testosterone secretion was also
      observed in basal and dbcAMP-stimulated conditions, suggesting that one site of
      action of TGF beta1 is located after the production of cAMP. However, TGF beta1
      was also able to inhibit LH-induced cAMP production. As demonstrated by the
      transformation of steroidogenic precursors into testosterone, TGF beta1 did not
      significantly alter 3beta-hydroxysteroid dehydrogenase (3beta HSD) activity but
      induced a strong inhibition of cytochrome P450 17alpha-hydroxylase/C17-20 lyase
      (P450C17) activity which was associated with a marked diminution of cytochrome
      P450C17 mRNA levels (26% of control values) but not of cytochrome P450scc mRNA.
      In addition to its effect on steroidogenesis, TGF beta1 exhibited morphogenic
      actions on the fetal testicular cells, inducing spreading when the cells were
      adherent and aggregation when the cells were cultured in conditions of lesser
      adherence and without any significant effect on either total cell number or 3beta
      HSD positive cells. Taken together these results suggest that TGF beta1 likely
      plays a morphogenic and physiological role very early in the fetal testis via
      paracrine/autocrine mechanisms.

PMID- 9256361
TI  - Removal of milk by suckling acutely increases the prolactin receptor gene
      expression in the lactating mouse mammary gland.
AB  - To determine the effect of suckling on the prolactin receptor (PRL-R) gene
      expression, we measured the quantity of PRL-R mRNA in the lactating mouse mammary
      gland. When the pups were separated from their mother on day 5 of lactation, the
      long form of PRL-R (PRL-R[L]) mRNA disappeared with a half-life of 12.5 h for the
      first 9 h and 3.0 h for the following 9-15 h. By supplying pups to mice which had
      been weaned for 24 h, PRL-R(L) mRNA increased 2.5-fold during the next 6 h
      period. The increase in PRL-R(L) mRNA was found in the mammary glands from which
      the pups removed milk. The number of mammary PRL-R protein decreased or increased
      following weaning or following the removal of milk by suckling, respectively.
      From these observations. it was concluded that the removal of milk acutely
      increases the level of PRL-R(L) mRNA during lactation.

PMID- 9256362
TI  - Sequence and developmental expression of Cyp18, a member of a new cytochrome P450
      family from Drosophila.
AB  - Preliminary studies of a partial cDNA clone of the Eig17-1 gene from Drosophila
      melanogaster have shown that it encodes a probable cytochrome P450 of unknown
      function. To further characterize the Eig17-1 gene product, a full-length cDNA
      clone was isolated from a late-larval cDNA library and sequenced. Eig17-1 encodes
      a protein of 538 amino acids. The predicted protein is a cytochrome P450 that has
      been assigned to a new family, CYP18. The CYP18 protein is most closely related
      to steroid and xenobiotic metabolizing P450s of family CYP2 (30-33% identity),
      and to vertebrate steroidogenic P450s of families CYP17 and CYP21 (25-28%
      identity). Developmental Northern blot analysis revealed five distinct periods of
      Cyp18 expression during postembryonic development. Each period lasted 12-15 h,
      and was tightly correlated with reported ecdysteroid pulses in the first, second
      and third larval instars, at the time of pupariation and in pupae. This pattern
      of expression is consistent with the known induction of Cyp18 transcription by 20
      hydroxyecdysone at the time of pupariation and suggests that ecdysteroids are
      major regulators of Cyp18 expression throughout postembryonic development.
      Northern blot analysis of RNA isolated from different prepupal tissues indicates
      that Cyp18 is differentially expressed in various ecdysteroid-responsive tissues.
      High Cyp18 expression was observed in body wall and gut while negligible
      expression was observed in salivary glands and fat body.

PMID- 9256363
TI  - Molecular expression of 17 beta hydroxysteroid dehydrogenase types in relation to
      their activity in intact human prostate cancer cells.
AB  - In the present study we have inspected estrogen metabolism in cultured human
      prostate cancer cells (LNCaP, DU145, PC3), in relation to the expression of mRNAs
      for different 17 beta hydroxysteroid dehydrogenase (17 beta HSD) enzymes (from 1
      to 4). Using an intact cell analysis, we have compared precursor degradation and
      product formation after incubation of cells with physiological amounts of
      radioactive E2 or estrone (E1) for 24-72 h and subsequent reverse-phase high
      performance liquid chromatography analysis. The LNCaP and DU145 cells only partly
      converted E2 to E1 (26 and 13% at 72 h, respectively), giving rise to an
      appreciable production of E2 from E1 (nearly 20% in all cases). Conversely, PC3
      cells revealed a massive E2 oxidation to E1 (up to 90% by 72 h) and a scant
      formation of E2 (<2%) from E1. In addition, an appreciable formation of 16 alpha
      OHE1 was seen in either PC3 (11%) or DU145 (5%) cells. respectively using E2 or
      E1 as precursor. All three cell lines exhibited marked amounts of 17 beta HSD4
      mRNA species, whilst even greater amounts of 17 beta HSD2 transcript were found
      in PC3 cells only. No mRNA for either 17 beta HSD1 or 17 beta HSD3 could be
      detected in any cell line. The present evidence indicates that pathways of
      estrogen metabolism are distinctly governed in prostate cancer cells depending on
      their endocrine status, being associated with a differential expression of mRNA
      for different 17 beta HSD enzymes.

PMID- 9256365
TI  - Expression of the two isoforms of prostaglandin endoperoxide synthase (PGHS-1 and
      PGHS-2) during adipose cell differentiation.
AB  - Expression of mRNAs encoding the two prostaglandin endoperoxide synthase (PGHS)
      isoenzymes (PGHS-1 and -2) was investigated in differentiating clonal Ob1771
      mouse preadipocytes and in mouse adipose tissues. Northern analysis revealed that
      the expression level of PGHS-1 mRNA was reduced by 98+/-0.2% (P <0.01) during
      differentiation of Ob1771 cells, whereas PGHS-2 mRNA was not detected. By reverse
      transcriptase-polymerase chain reaction analysis, however, both PGHS-1 and -2
      mRNA was detected in Ob1771 preadipose cells. In addition. mRNAs encoding both
      isoforms were markedly expressed in primary adipose precursor cells with
      considerably lower expression levels in mature adipocytes (56 75% reduction,
      P<0.01). Furthermore, exposure to dexamethasone (10 nM) for both 24 h (explants
      of adipose tissue) and 48 h (Ob1771 adipose cells) resulted in enhanced
      expression of PGHS-1 mRNA. whereas expression of PGHS-2 mRNA in explants of
      adipose tissue (24 h incubation) was reduced by 83 +/- 9% (P<0.05). In contrast,
      exposure to angiotensin II (100 nM) enhanced expression of PGHS-1 mRNA both in
      mature adipocytes (4 h incubation) and explants of adipose tissue (24 h
      incubation), and elevated PGHS-2 mRNA expression in mature adipocytes (4 h
      incubation). In conclusion, this report suggests a differential expression of
      PGHS mRNAs during adipose cell differentiation, and further suggests that the
      machinery for prostaglandin synthesis in mature adipocytes may be induced by
      various hormones.

PMID- 9256364
TI  - Modification of thyroid hormone and 9-cis retinoic acid signaling by
      overexpression of their cognate receptors using adenoviral vector.
AB  - Tissue responsiveness to a hormone is dependent on the amounts of its receptor
      expressed under physiological conditions. In the present report, we compared the
      magnitude of ligand-dependent transactivation mediated by two nuclear hormone
      receptors, thyroid hormone receptor beta (TR) and retinoid X receptor alpha
      (RXR), when overexpressed in a variety of cell lines. TR, RXR and reporter
      (luciferase) genes under the control of artificial hormone response elements were
      introduced into the cells using recombinant adenovirus (Ad) vectors, to ensure
      highly efficient gene delivery. Although the amounts of TR expressed were similar
      in the cell lines infected with Ad-TR, T3 dependent induction of reporter gene
      expression was significantly greater in HepG2 than in Cos7, GH3, or JEG3 cells,
      indicating that factors other than TR are limiting the responsiveness to T3. The
      enhanced response to 9-cis retinoic acid in cells overexpressing RXR was much
      greater in JEG3 than in HepG2 which had the highest responsiveness to T3 under TR
      overexpression. These results indicate that the factors affecting T3
      responsiveness are not identical to those affecting the 9-cis retinoic acid
      responsiveness. On the other hand, overexpression of RXR in addition to TR
      resulted in a decrease in T3-responsiveness in all the cell lines tested,
      suggesting that some cofactors are common to TR and RXR.

PMID- 9256366
TI  - Purkinje cell protein-2 cis-elements mediate repression of T3-dependent
      transcriptional activation.
AB  - Previous studies in our laboratory show that triiodothyronine upregulates
      expression of the cerebellar Purkinje cell-specific gene Pcp-2 during the first 2
      weeks of rat neonatal life. A specific thyroid hormone response element, the A1
      TRE, mediates this regulation. The finding that the contiguous 68 bases (-267/ 
      199) of the Pcp-2 promoter 3' to the A1 TRE repressed T3 response in
      transactivation studies suggested that this sequence could play a role in
      preventing premature T3-dependent activation of Pcp-2 in the fetus. We now show
      that deletion of this region resulted in enhanced T3-dependent activation of the
      native Pcp-2 promoter. The sequence is not a generalized silencer since it does
      not alter basal activity of mouse mammary tumor virus (MMTV) or thymidine kinase
      (TK) promoters. Deletion and linker scanning studies indicate that the 5' 30
      bases of the -267/ -199 region mediate most of the response silencing activity.
      The -267/ -199 region also attenuates T3-induced transactivation mediated by
      other TREs. Gel shift analysis reveals that nuclear proteins from fetal but not
      adult brains complex with the -267/ -199 region, supporting the hypothesis that
      this region binds proteins that suppress Pcp-2 expression early in brain
      development.

PMID- 9256367
TI  - Regulation of human growth hormone receptor gene transcription by human growth
      hormone binding protein.
AB  - The hypothesis that growth hormone binding protein (GHBP) has an effect on its
      own on the regulation of the GH-receptor/GHBP transcription was tested. Three
      different forms of human GHBP (recombinant non-glycosylated GHBP, recombinant
      glycosylated GHBP and GHBP purified and extracted from serum) were added in
      different concentrations determined by LIFA [0 pmol/l; 50 pmol/l (low level), 200
      pmol/l (average level) and 500 pmol/l (high level in circulation)] to a human
      hepatoma cell line (HuH7 cells) cultured in a serum free hormonally-defined
      medium. Following the incubation with GHBP for 0, 1 and 2 h, GH-receptor
      expression was quantitatively assessed by using polymerase chain reaction
      amplification. Treatment with a GHBP concentration of 50 pmol/l resulted in a
      significant increase of GH-receptor mRNA molecules given as number of molecules x
      10(6)/microg total RNA. In contrast, the concentration of 500 pmol/l presented a
      significant decrease of GH-receptor mRNA molecules, whereas 200 pmol/l GHBP
      produced a GH-receptor gene expression which was in between the values of the
      experiments with 50 and 500 pmol/l of GHBP added. Furthermore, the three
      different forms of human GHBP used provided similar data and, therefore, did not
      effect in any variation of GH-receptor expression. In addition, nuclear run-on
      experiments confirmed the changes in GH-receptor expression; and cycloheximide
      (10 microg/ml) did not alter the transcription indicating that the up and down
      regulating effects of GHBP on the GH-receptor/GHBP gene transcription was
      dependent, at least partly, on pre-existing factors and does not require protein
      synthesis. In conclusion, we present data showing that GHBP on its own has an
      effect on GH-receptor gene expression.

PMID- 9256369
TI  - Involvement of both calcium influx and calcium mobilization in growth hormone
      induced [Ca2+]i increases in Chinese hamster ovary cells.
AB  - This study reports rapid effects of growth hormone (GH) on the intracellular free
      calcium concentration ([Ca2+]i) in Chinese hamster ovary (CHO) cells stably
      expressing rabbit GH receptor. [Ca2+]i was measured by spectrofluorimetric
      methods in single cells and membrane Ca2+ currents by patch clamp techniques in
      the whole-cell configuration. In individual CHO cells, bathed in a standard
      saline solution containing 2 mM Ca2+, basal [Ca2+]i was 191 +/- 27 nM (mean +/-
      S.D.; n=83). Short term administration of GH (100 ng/ml, 30 s) induced a [Ca2+]i
      increase in 54% of cells tested (n = 398 of 743). Responses were clearly
      heterogeneous. Maximum calcium increase varied from 16 to 853 nM and time to peak
      varied from 4 to 320 s. On examination of the [Ca2+]i increases, it was possible
      to define two different types of calcium responses to GH. Experimental
      manipulations of extracellular and intracellular calcium concentrations
      demonstrated that GH-induced calcium increases involved both calcium influx and
      calcium mobilization. Calcium influx, a long lasting, small amplitude (63 +/- 34
      nM) response, was observed in 121 out of 398 cells (30%) whereas calcium
      mobilization, a transient, large amplitude (263 +/- 175 nM) response, was
      observed in 277 out of 398 cells (70%). Moreover, patch clamp data show that
      influx did not involve the dihydropyridine-sensitive calcium channels.

PMID- 9256368
TI  - A novel regulation of the oviductal glycoprotein gene expression by luteinizing
      hormone in bovine tubal epithelial cells.
AB  - The hypothesis that bovine oviductal epithelial cells contain luteinizing hormone
      (LH)/human chorionic gonadotropin (hCG) receptors and LH may regulate the
      oviductal glycoprotein (OGP) gene expression was tested. The results showed that
      bovine oviductal epithelial cells contain an 80 kDa LH/hCG receptor protein which
      can bind [(125)I]hCG. Culturing these cells with highly purified hCG, used as a
      surrogate hormone for LH, resulted in a dose and time dependent increase in a 95
      kDa protein and a 2.3 kb transcript of OGP. The maximal increase of 100% was
      obtained with 10 ng/ml hCG and after three days of culture. LH, but not other
      hormones in the glycoprotein hormone family, isolated subunits of hCG, estradiol
      17beta or progesterone, mimicked hCG, suggesting that the effect is hormone
      specific and requires the conformation of native hormone. The increase in steady
      state OGP mRNA levels by hCG is not due to an increase in the transcription rate
      of the gene. It is rather due to a significant increase in the half-life of OGP
      transcripts from 23 h in the control to 28 h after treatment with hCG. In
      summary, we conclude that LH and hCG can increase the synthesis of OGP by
      decreasing the degradation of its transcripts in bovine oviductal epithelial
      cells. Since OGP may play important roles in fertilization and growth and
      development of early embryo, higher LH levels present during the periovulatory
      period may directly participate in the early pregnancy events through increasing
      the synthesis of OGP.

PMID- 9256370
TI  - Automatic semantic priming of nouns and verbs in patients with Alzheimer's
      disease.
AB  - The status of semantic representations of nouns (concrete and abstract) and verbs
      (motion and non-motion) was investigated in patients with Alzheimer's disease
      (AD). Nouns and verbs have been argued to activate different neural substrates,
      given the selective difficulties reported for one or the other grammatical class
      in patients with focal lesions. Additionally, category-specific deficits have
      been reported for either abstract or concrete words, often in patients with
      bilateral neuropathology. We looked for these types of dissociations in patients
      with AD in a semantic priming experiment using a pronunciation task and a short
      stimulus onset asynchrony. The normal control subjects demonstrated automatic
      activation for both concrete nouns and motion verbs. The AD patients, however,
      demonstrated priming effects for concrete nouns, but not for motion verbs. This
      dissociation between concrete nouns and motion verbs found for the AD patients is
      discussed in terms of differences in the nature of semantic representations
      involving multiple physical and functional attributes in the case of concrete
      nouns, but only motion attributes in the case of motion verbs. Moreover, the
      typical distribution of neuropathology associated with AD may put motion verbs at
      risk, particularly given the neuroanatomical considerations suggested by recent
      positron emission tomography (PET) studies.

PMID- 9256371
TI  - Preserved verb generation priming in global amnesia.
AB  - In the verb generation task, participants are presented with nouns and generate
      for each one an appropriate verb. Raichle et al. (Cerebral Cortex, 1994, 4, 8-26)
      found that when participants generated verbs to repeated nouns, generation
      latencies were reduced and different patterns of brain activation were present.
      In order to examine whether verb generation priming is dependent or independent
      of declarative memory, verb generation priming was compared between 13 amnesic
      (seven with alcoholic Korsakoff's syndrome, six with other etiologies) and 19
      control participants (10 with a history of alcoholism). Both amnesic and control
      participants became faster across blocks on repeated nouns and slowed when novel
      nouns were introduced. Priming was verb specific for both groups: it was
      equivalent whether generated to a repeated or a novel noun. Verb generation
      priming, therefore, can occur independently of declarative memory.

PMID- 9256372
TI  - Lexical and semantic processing in the absence of word reading: evidence from
      neglect dyslexia.
AB  - Nine patients with left-sided neglect and nine matched control patients performed
      three tasks on horizontal (either normal or mirror-reversed) letter strings. The
      tasks were: reading aloud, making a lexical decision (word vs non-word), and
      making a semantic decision (living vs non-living item). Relative to controls,
      neglect patients performed very poorly in the reading task, whereas they
      performed nearly normally in the lexical and semantic tasks. This was considered
      to be a dissociation between direct tasks, rather than a dissociation between
      explicit and implicit knowledge. The explanation offered for the dissociation is
      in terms of both a dual-route model for reading aloud and a degraded
      representation of the letter string.

PMID- 9256373
TI  - Impaired word-stem priming in patients with temporal-occipital lesions.
AB  - In the word-stem priming test, words are presented (e.g., MOTEL, PARADE), and
      later subjects are shown three-letter word stems (e.g., MOT, PAR) and asked to
      complete each stem with the first word that comes to mind. Word-stem priming, as
      well as other aspects of implicit memory, are intact in amnesic patients with
      medial temporal lesions. However, this form of priming has been shown to be
      impaired in patients with Alzheimer's disease, suggesting that damage to
      neocortical areas outside the medial temporal lobe contributes to impaired
      priming in these patients. To examine the role of posterior cortical areas on
      word-stem priming, we administered the test to patients with unilateral temporal
      occipital lesions. Patients with temporal-occipital lesions exhibited
      significantly impaired priming on this test. The findings suggest a critical role
      of the inferior posterior neocortex in the expression of this form of implicit
      memory.

PMID- 9256374
TI  - The effect of anterior thalamic and cingulate cortex lesions on object-in-place
      memory in monkeys.
AB  - Six Macaque monkeys (Macaca mulatta) were trained in an object-in-place memory
      task, designed to capture the 'whole scene' nature of episodic memory. In this
      task the correct, rewarded, response in each scene was to a particular object of
      a pair, which always occupied a particular position in a unique background which
      had been generated using randomly chosen colours and shapes. In each session, the
      monkey learned a new list of these unique scenes. The animals then underwent
      surgical ablation of either the anterior thalamic nuclei or the cingulate cortex.
      It was found that the animals with anterior thalamic lesions showed a substantial
      impairment, whereas the monkeys with cingulate cortex ablations were not
      significantly impaired at the task. These results confirm the importance of the
      anterior thalamic nuclei in episodic memory, and suggest that the cingulate gyrus
      is not a region which is crucial in the type of episodic memory task used in the
      present experiment.

PMID- 9256375
TI  - Errorless learning of novel associations in amnesia.
AB  - In two experiments involving verbal association learning by people with memory
      impairments, the effectiveness of errorless learning (EL) was compared with
      errorful learning (EF). Experiment 1 examined the effectiveness of both methods
      in learning remotely linked word pairs. There was an advantage for items learned
      by EL at immediate test which was not sustained over a delay of 1 hr. Learning
      appeared to be stable over this delay in the EF condition. Analysis of responses
      at delayed cued recall showed more evidence of spontaneous recovery in EF than in
      EL. Elimination of these items from analysis resulted in a similar pattern of
      forgetting in both methods. Experiment 2 examined the effectiveness of EL and EF
      in teaching novel associations, and showed an advantage for EL at immediate and
      delayed test. Forgetting was apparently observed following EL, but not EF. As in
      Experiment 1, this discrepancy was attributed to recovered responses at delayed
      test in EF. Eliminating these responses showed a similar pattern of forgetting in
      both methods for items correctly recalled at immediate test. The study shows an
      advantage for EL techniques in learning novel associations. The two methods also
      differ in that learning via EF is associated with more spontaneous recovery.

PMID- 9256376
TI  - Backward masking of words and faces: evidence for different processing speeds in
      the hemispheres?
AB  - Two tachistoscopic experiments with a lateralized presentation of function words
      and faces were carried out to investigate the influence of temporal factors and
      type of masking on visual field asymmetries. Accuracy, represented by signal
      detection measures (d' and beta), was calculated separately for the two visual
      fields, for various interstimulus intervals, and for noise and pattern masking.
      In both experiments, d' increased with prolonged temporal delay between target
      and mask. In the lexical decision task, visual field interacted with mask type
      confirming that only in the pattern mask condition did an advantage of the right
      visual field emerge. In the facial decision task, however, visual field
      interacted with interstimulus interval, confirming that, in the left visual
      field, the facial information escaped the masking effect earlier than in the
      right visual field. In the facial task, there was a higher response criterion
      (beta) in the left visual field. By applying different types of masks, visual
      processing of lexical stimuli can be disrupted at distinct stages where
      perceptual asymmetries are present to a varying extent. The results of both
      experiments suggest that words and faces are differentially affected by masking
      procedures.

PMID- 9256377
TI  - Temporal aspects of visual search studied by transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation was applied over the parietal visual cortex of
      subjects while they were performing 'pop-out' or conjunction visual search tasks
      in arrays containing eight distractors. Magnetic stimulation had no detrimental
      effect on the performance of pop-out search, but did significantly increase
      reaction times on conjunction search when stimulation was applied over the right
      parietal cortex 100 msec after the onset of the visual display for trials when
      the target was present. Target absent reaction times were elevated when
      stimulation was applied 160 msec after array onset. Stimulation had no effect on
      the number of errors made. The results suggest that a sub-region of the right
      parietal lobe is important for conjunction search but not for pre-attentive pop
      out. The result from target present trials is consistent with timing data from
      studies of single cells in monkeys and the hypothesis that parietal areas
      generate a signal that projects back to extrastriate visual areas to enhance the
      processing of features in a restricted part of the visual field. The timing of
      the effect indicates that transcranial stimulation disrupts the mechanisms
      underlying the focal attention necessary for feature binding in conjunction
      search. The effects of TMS on target absent trials are interpreted in terms of
      fronto-parietal connections and the role of frontal cortex in decision-making.
      The results also highlight the efficacy of transcranial magnetic stimulation as a
      complement to other spatial and temporal imaging techniques.

PMID- 9256378
TI  - Deficit in figure-ground segmentation following closed head injury.
AB  - Patient CB showed a severe impairment in figure-ground segmentation following a
      closed head injury. Unlike normal subjects, CB was unable to parse smaller and
      brighter parts of stimuli as figure. Moreover, she did not show the normal effect
      that symmetrical regions are seen as figure, although she was able to make overt
      judgments of symmetry. Since she was able to attend normally to isolated objects,
      CB demonstrates a dissociation between figure ground segmentation and subsequent
      processes of attention. Despite her severe impairment in figure-ground
      segmentation, CB showed normal 'parallel' single feature visual search. This
      suggests that figure-ground segmentation is dissociable from 'preattentive'
      processes such as visual search.

PMID- 9256379
TI  - Magnetoencephalographic evidence for non-geniculostriate visual input to human
      cortical area V5.
AB  - The aim of this study was to establish whether there is non-geniculostriate input
      to the extrastriate motion-sensitive area V5 in humans. Responses were measured
      with a SQUID neuro-magnetometer to motion stimuli presented within the blind
      hemifield of GY, a well-documented subject with a complete absence of the left
      primary visual cortical area V1. The motion stimulus was a 0.5c/deg, rapidly
      drifting (16Hz) achromatic sinusoidal grating. With this stimulus, the magnetic
      responses recorded over the temporo-parieto-occipital region in normals are well
      modelled by localized current sources in areas V1 and V5 (Anderson, S. J. et al.,
      Proceedings of the Royal Society, London, Series B, 1996, 263, 423-431). As a
      control, evoked responses were measured to a 1.0 c/deg, stationary,
      photometrically isoluminant red/green sinusoidal grating. With the chromatic
      stimulus, the principal component of the magnetic responses recorded over the
      occipital pole in normals is well modelled by a current source in area V1 (Fylan,
      F. et al., Investigative Ophthalmology and Visual Science, 1995, 36, s1053). Both
      stimuli subtended 4 deg vertically by 6 deg horizontally, positioned such that
      the stimulus extended beyond the area of macular sparing into the lower field
      quadrant of the blind (or sighted) hemifield. Chromatic stimuli failed to evoked
      responses from GY's blind (contralateral) hemifield, consistent with there being
      no V1 activity in his left cortical hemisphere. However, motion stimuli did evoke
      responses from GY's blind hemifield, originating from a location consistent with
      activity in area V5. We further observed that both colour and motion stimuli
      evoked responses from GY's sighted (ipsilateral) hemifield. We conclude that
      there is non-geniculostriate input to extrastriate motion-sensitive areas in the
      human visual system, and that this pathway subserves the residual visual
      sensitivity to motion in the blind hemifield that has been demonstrated
      psychophysically in observer GY.

PMID- 9256380
TI  - The effect of goal-subgoal conflict on planning ability after frontal- and
      temporal-lobe lesions in humans.
AB  - Twenty-one patients with unilateral prefrontal cortical neurosurgical lesions (11
      left and 10 right) and 38 patients with unilateral temporal lobectomy (19 left
      and 19 right) were compared to 44 matched control subjects on their performance
      on the 3-D Computerized Tower of Hanoi (3-D CTOH) test. The problems were split
      into those with or without a significant goal-subgoal conflict determined by
      whether the correct first move in each problem took the subject apparently away
      or towards the final goal state. The left frontal lesion and right temporal
      lobectomy groups were significantly impaired on problems with goal-subgoal
      conflicts. In the left frontal group, this deficit was confined to earlier four
      move problems, whereas the right temporal group showed a more general deficit on
      later five-move problems. The left frontal lesion deficit is explained in terms
      of an inability to inhibit the response compatible with achieving a final goal,
      whereas the impairment in the right lesion group was related to a specific
      impairment in spatial memory.

PMID- 9256382
TI  - Line bisection with a head-mounted pointing device: an investigation of the role
      of right hand use and bilateral hemisphere activation in left neglect.
AB  - Left hand use in left hemispace has been shown to reduce left neglect. Right hand
      use can theoretically increase neglect by right spatial cueing and left
      hemisphere activation. The aim of the present study was to investigate the role
      of right hand use and right hemisphere activation in left neglect by dissociating
      hemisphere activation from the hemispace in which the motor response is made.
      Twelve neglect patients performed line bisection by two means: with their right
      hand and with a lamp mounted centrally on the forehead ('miner's lamp'). Lamp use
      induces left and right hemisphere activation without hemispace involvement.
      Bisection with the lamp and the hand were done with right, left and neutral cues.
      No difference was found in bisection performance between lamp and right hand use,
      and no interaction between lamp/hand use and cueing. This indicates that right
      hand use per se does not influence neglect in line bisection. It is suggested
      that the apparent lack of right hemisphere activation with lamp use is due to the
      widespread right-sided lesion of the typical neglect patient.

PMID- 9256381
TI  - Isolation of a right hemisphere cognitive system in a patient with anarchic
      (alien) hand sign.
AB  - We report evidence of isolated conceptual knowledge in the right hemisphere of a
      woman with chronic anarchic hand sign after ischemic infarction of the central
      four-fifths of the corpus callosum. Limited visual information was available to
      the right hemisphere, access to medial temporal structures subserving memory was
      disrupted and disconnection from left hemisphere language structures was
      complete. Still, the right hemisphere could build mental representations of
      objects via tactile input and use them in cross-modal matching. These
      representations were not accessed consistently in auditory comprehension or
      naming tasks. This functional specificity and its pathoanatomical correlates
      demonstrate that the study of anarchic hand sign can illuminate not just motor
      control issues but may inform our understanding of the representation and
      lateralization of conceptual knowledge as well.

PMID- 9256383
TI  - Blood flow velocity changes in the middle cerebral artery induced by processing
      of hierarchical visual stimuli.
AB  - Transcranial Doppler ultrasound was used to measure mean flow velocities in both
      middle cerebral arteries while 16 young subjects performed a visual task
      involving the processing of hierarchically structured stimuli. Specifically,
      large (global) letters composed of smaller (local) letters were presented, with
      the subjects' task being to attend either to the local or to the global level and
      press a button whenever a target on the designated level occurred. Each run was
      comprised of a 35-sec period of passive stimulation, followed by 65 sec of active
      task. A highly significant increase of blood flow was detected upon initiation of
      the active task, which was clearly present after ca. 4 sec. The flow velocity
      reached a maximum after 20 sec and remained stable for the remainder of the
      active condition. No hemispheric differences with respect to global or local
      conditions were observed.

PMID- 9256385
TI  - Induction of cytochrome P450 in Hep G2 cells and mutagenicity of extracts of
      sediments from a waste disposal site near Osaka, Japan.

PMID- 9256386
TI  - Biodegradation of Lindane by Pleurotus sajor-caju and toxic effects of Lindane
      and its metabolites on mice.

PMID- 9256384
TI  - Dramatic fluctuations in liver mass and metal content of eared grebes (Podiceps
      nigricollis) during autumnal migration.

PMID- 9256387
TI  - Serum testosterone and sexual behavior in rats after prenatal exposure to
      lindane.

PMID- 9256388
TI  - Photochemical transformation of the fungicide chlorothalonil by ultra violet
      radiation.

PMID- 9256389
TI  - Laboratory and field enzyme-immunoassays for diazinon and their application to
      residue analysis in lanolin, water, and fruit juice.

PMID- 9256390
TI  - Dieldrin and chlordane residue in agriculture fields.

PMID- 9256391
TI  - Qualitative and quantitative analysis of diazinon in fabric exposed to various
      simulated sunlight and humidity conditions.

PMID- 9256392
TI  - Hair: a matrix for non-invasive biomonitoring of organic chemicals in mammals.

PMID- 9256393
TI  - Levels of HCH residues in human milk samples from Delhi, India.

PMID- 9256394
TI  - Effect of age and number of deliveries on mean concentration of organochlorine
      compounds in human breast milk in Poland.

PMID- 9256395
TI  - Diurnal fluctuations in toxicity in two fish species: Gambusia affinis and
      Notropis ludibundis.

PMID- 9256396
TI  - Prediction of bioaccumulation potential of some aromatic hydrocarbons in
      indicator species of ecotoxicity.

PMID- 9256397
TI  - Hydrocarbon concentrations in oysters (Crassostrea virginica) and recent
      sediments from three coastal lagoons in Tabasco, Mexico.

PMID- 9256398
TI  - Impact of fuel oil on the freshwater alga Selenastrum capricornutum.

PMID- 9256399
TI  - Acute sensitivity of three age classes of Artemia salina larvae to seven
      chlorinated solvents.

PMID- 9256400
TI  - Elimination of PCBs from heavily contaminated carp (Cyprinus carpio L) in clean
      water-depuration study.

PMID- 9256401
TI  - Fertilization of eggs of Lake Michigan lake trout Salvelinus namaycush in lake
      water: effect of PCBs (Aroclor 1254).

PMID- 9256402
TI  - Effects of culture duration on toxicity of ethanol to developing embryos of the
      grass shrimp, Palaemonetes pugio.

PMID- 9256403
TI  - Mercury and polychlorinated biphenyls in zooplankton and shrimp from the Barents
      Sea and the Spitsbergen area.

PMID- 9256404
TI  - Oxygen consumption of juvenile rainbow trout (Oncorhynchus mykiss) exposed to
      sublethal concentrations of 1,2,4,5-tetrachlorobenzene and tetrachloroguaiacol.

PMID- 9256405
TI  - Detergents and orthophosphates inputs from urban discharges to Chetumal Bay,
      Quintana Roo, Mexico.

PMID- 9256406
TI  - Single species algal (Ankistrodesmus) toxicity tests with Rodeo and Garlon 3A.

PMID- 9256407
TI  - Influence of copper, zinc, and iron on cadmium accumulation in the talitrid
      amphipod, Platorchestia platensis.

PMID- 9256409
TI  - Pigment, platelets, and Hermansky-Pudlak in human and mouse.

PMID- 9256410
TI  - Lymphotoxins: from cytotoxicity to lymphoid organogenesis.

PMID- 9256413
TI  - Antibody-mediated inhibition of the growth of larvae from an insect causing
      cutaneous myiasis in a mammalian host.
AB  - Many insects feed on blood or tissue from mammalian hosts. One potential strategy
      for the control of these insects is to vaccinate the host with antigens derived
      from the insect. The larvae of the fly Lucilia cuprina feed on ovine tissue and
      tissue fluids causing a cutaneous myiasis associated with considerable host
      morbidity and mortality. A candidate vaccine antigen, peritrophin 95, was
      purified from the peritrophic membrane, which lines the gut of these larvae.
      Serum from sheep vaccinated with peritrophin 95 inhibited growth of first-instar
      L. cuprina larvae that fed on this serum. Growth inhibition was probably caused
      by antibody-mediated blockage of the normally semipermeable peritrophic membrane
      and the subsequent development of an impervious layer of undefined composition on
      the gut lumen side of the peritrophic membrane that restricted access of
      nutrients to the larvae. The amino acid sequence of peritrophin 95 was determined
      by cloning the DNA complementary to its mRNA. The deduced amino acid sequence
      codes for a secreted protein containing a distinct Cys-rich domain of 317 amino
      acids followed by a mucin-like domain of 139 amino acids. The Cys-rich domain may
      be involved in binding chitin. This report describes a novel immunological
      strategy for the potential control of L. cuprina larvae that may have general
      application to the control of other insect pests.

PMID- 9256414
TI  - Whole genome analysis: experimental access to all genome sequenced segments
      through larger-scale efficient oligonucleotide synthesis and PCR.
AB  - The recent ability to sequence whole genomes allows ready access to all genetic
      material. The approaches outlined here allow automated analysis of sequence for
      the synthesis of optimal primers in an automated multiplex oligonucleotide
      synthesizer (AMOS). The efficiency is such that all ORFs for an organism can be
      amplified by PCR. The resulting amplicons can be used directly in the
      construction of DNA arrays or can be cloned for a large variety of functional
      analyses. These tools allow a replacement of single-gene analysis with a highly
      efficient whole-genome analysis.

PMID- 9256411
TI  - Considerations of transcriptional control mechanisms: do TFIID-core promoter
      complexes recapitulate nucleosome-like functions?
AB  - The general transcription initiation factor TFIID was originally identified,
      purified, and characterized with a biochemical assay in which accurate
      transcription initiation is reconstituted with multiple, chromatographically
      separable activities. Biochemical analyses have demonstrated that TFIID is a
      multiprotein complex that directs preinitiation complex assembly on both TATA box
      containing and TATA-less promoters, and some TFIID subunits have been shown to be
      molecular targets for activation domains in DNA-binding regulatory proteins.
      These findings have most commonly been interpreted to support the view that
      transcriptional activation by upstream factors is the result of enhanced TFIID
      recruitment to the core promoter. Recent insights into the architecture and cell
      cycle regulation of the multiprotein TFIID complex prompt both a reassessment of
      the functional role of TFIID in gene activation and a review of some of the less
      well-appreciated literature on TFIID. We present a speculative model for diverse
      functional roles of TFIID in the cell, explore the merits of the model in the
      context of published data, and suggest experimental approaches to resolve
      unanswered questions. Finally, we point out how the proposed functional roles of
      TFIID in eukaryotic class II transcription fit into a model for promoter
      recognition and activation that applies to both eubacteria and eukaryotes.

PMID- 9256415
TI  - Stimulation of neurite outgrowth using an electrically conducting polymer.
AB  - Damage to peripheral nerves often cannot be repaired by the juxtaposition of the
      severed nerve ends. Surgeons have typically used autologous nerve grafts, which
      have several drawbacks including the need for multiple surgical procedures and
      loss of function at the donor site. As an alternative, the use of nerve guidance
      channels to bridge the gap between severed nerve ends is being explored. In this
      paper, the electrically conductive polymer--oxidized polypyrrole (PP)--has been
      evaluated for use as a substrate to enhance nerve cell interactions in culture as
      a first step toward potentially using such polymers to stimulate in vivo nerve
      regeneration. Image analysis demonstrates that PC-12 cells and primary chicken
      sciatic nerve explants attached and extended neurites equally well on both PP
      films and tissue culture polystyrene in the absence of electrical stimulation. In
      contrast, PC-12 cells interacted poorly with indium tin oxide (ITO), poly(L
      lactic acid) (PLA), and poly(lactic acid-co-glycolic acid) surfaces. However, PC
      12 cells cultured on PP films and subjected to an electrical stimulus through the
      film showed a significant increase in neurite lengths compared with ones that
      were not subjected to electrical stimulation through the film and tissue culture
      polystyrene controls. The median neurite length for PC-12 cells grown on PP and
      subjected to an electrical stimulus was 18.14 micron (n = 5643) compared with 9.5
      micron (n = 4440) for controls. Furthermore, animal implantation studies reveal
      that PP invokes little adverse tissue response compared with poly(lactic acid-co
      glycolic acid).

PMID- 9256416
TI  - Three functional luciferase domains in a single polypeptide chain.
AB  - We report a unique case of a gene containing three homologous and contiguous
      repeat sequences, each of which, after excision, cloning, and expression in
      Escherichia coli, is shown to code for a peptide catalyzing the same reaction as
      the native protein, Gonyaulax polyedra luciferase (Mr = 137). This enzyme, which
      catalyzes the light-emitting oxidation of a linear tetrapyrrole (dinoflagellate
      luciferin), exhibits no sequence similarities to other luciferases in databases.
      Sequence analysis also reveals an unusual evolutionary feature of this gene:
      synonymous substitutions are strongly constrained in the central regions of each
      of the repeated coding sequences.

PMID- 9256417
TI  - The N-terminal tail of histone H2A binds to two distinct sites within the
      nucleosome core.
AB  - Each of the core histone proteins within the nucleosome has a central
      "structured" domain that comprises the spool onto which the DNA superhelix is
      wrapped and an N-terminal "tail" domain in which the structure and molecular
      interactions have not been rigorously defined. Recent studies have shown that the
      N-terminal domains of core histones probably contact both DNA and proteins within
      the nucleus and that these interactions play key roles in the regulation of
      nuclear processes (such as transcription and replication) and are critical in the
      formation of the chromatin fiber. An understanding of these complex mechanisms
      awaits identification of the DNA or protein sites within chromatin contacted by
      the tail domains. To this end, we have developed a site-specific histone protein
      DNA photocross-linking method to identify the DNA binding sites of the N-terminal
      domains within chromatin complexes. With this approach, we demonstrate that the N
      terminal tail of H2A binds DNA at two defined locations within isolated
      nucleosome cores centered around a position approximately 40 bp from the
      nucleosomal dyad and that this tail probably adopts a defined structure when
      bound to DNA.

PMID- 9256418
TI  - Versatile 5' phosphoryl coupling of small and large molecules to an RNA.
AB  - A Ca2+-requiring catalytic RNA is shown to create 5' phosphate-phosphate linkages
      with all nucleotides and coenzymes including CoA, nicotinamide adenine
      dinucleotide phosphate, thiamine phosphate, thiamine pyrophosphate, and flavin
      mononucleotide. In addition to these small molecules, macromolecules such as RNAs
      with 5'-diphosphates, and nonnucleotide molecules like Nepsilon-phosphate
      arginine and 6-phosphate gluconic acid also react. That is, the self-capping RNA
      isolate 6 is an apparently universal 5' phosphate-linker, reacting with any
      nucleophile containing an unblocked phosphate. These RNA reactions demonstrate a
      unique RNA catalytic capability and imply versatile and specific
      posttranscriptional RNA modification by RNA catalysis.

PMID- 9256419
TI  - The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S
      proteasome.
AB  - Processing of antigens for presentation by major histocompatibility complex (MHC)
      class I molecules requires the activity of the proteasome. The 20S proteasome
      complex is composed of 14 different subunits, 2 of which can be substituted by
      the interferon gamma (IFN-gamma)-inducible and MHC-encoded subunits LMP2 and LMP7
      (low molecular mass poylpeptides 2 and 7). A third subunit, MECL-1, is inducible
      by IFN-gamma but is encoded outside the MHC. Here we show by cotransfection
      experiments that the incorporation of MECL-1 into the 20S proteasome is directly
      dependent on the expression of LMP2 but independent of LMP7. Conversely, the
      uptake of LMP2 is strongly enhanced by MECL-1 expression. The expression of MECL
      1 caused a replacement of the homologous subunit Z in the 20S proteasome complex.
      LMP2 is required for MECL-1 incorporation at the level of proteasome precursor
      formation that guarantees the concerted incorporation of two IFN-gamma-inducible
      proteasome subunits encoded inside and outside the MHC. The obligatory
      coincorporation of MECL-1 and LMP2 is an important parameter for the
      interpretation of results obtained with LMP2-deficient cell lines and mice as
      well as for the design of experiments addressing the function of MECL-1 in
      antigen presentation.

PMID- 9256420
TI  - Recognition principle of the TAP transporter disclosed by combinatorial peptide
      libraries.
AB  - Transport of peptides across the membrane of the endoplasmic reticulum for
      assembly with MHC class I molecules is an essential step in antigen presentation
      to cytotoxic T cells. This task is performed by the major histocompatibility
      complex-encoded transporter associated with antigen processing (TAP). Using a
      combinatorial approach we have analyzed the substrate specificity of human TAP at
      high resolution and in the absence of any given sequence context, revealing the
      contribution of each peptide residue in stabilizing binding to TAP. Human TAP was
      found to be highly selective with peptide affinities covering at least three
      orders of magnitude. Interestingly, the selectivity is not equally distributed
      over the substrate. Only the N-terminal three positions and the C-terminal
      residue are critical, whereas effects from other peptide positions are
      negligible. A major influence from the peptide backbone was uncovered by peptide
      scans and libraries containing D amino acids. Again, independent of peptide
      length, critical positions were clustered near the peptide termini. These
      approaches demonstrate that human TAP is selective, with residues determining the
      affinity located in distinct regions, and point to the role of the peptide
      backbone in binding to TAP. This binding mode of TAP has implications in an
      optimized repertoire selection and in a coevolution with the major
      histocompatibility complex/T cell receptor complex.

PMID- 9256421
TI  - Activities and response to DNA damage of latent and active sequence-specific DNA
      binding forms of mouse p53.
AB  - The mouse p53 protein generated by alternative splicing (p53as) has amino acid
      substitutions at its C terminus that result in constitutively active sequence
      specific DNA binding (active form), whereas p53 protein itself binds
      inefficiently (latent form) unless activated by C-terminal modification.
      Exogenous p53as expression activated transcription of reporter plasmids
      containing p53 binding sequences and inhibited growth of mouse and human cells
      lacking functional endogenous p53. Inducible p53as in stably transfected p53 null
      fibroblasts increased p21(WAF1/Cip-1/Sdi) and decreased bcl-2 protein steady
      state levels. Endogenous p53as and p53 proteins differed in response to cellular
      DNA damage. p53 protein was induced transiently in normal keratinocytes and
      fibroblasts whereas p53as protein accumulation was sustained in parallel with
      induction of p21(WAF1/Cip-1/Sdi) protein and mRNA, in support of p53as
      transcriptional activity. Endogenous p53 and p53as proteins in epidermal tumor
      cells responded to DNA damage with different kinetics of nuclear accumulation and
      efficiencies of binding to a p53 consensus DNA sequence. A model is proposed in
      which C-terminally distinct p53 protein forms specialize in functions, with
      latent p53 forms primarily for rapid non-sequence-specific binding to sites of
      DNA damage and active p53 forms for sustained regulation of transcription and
      growth.

PMID- 9256422
TI  - Loss of heterozygosity induced by a chromosomal double-strand break.
AB  - The repair of chromosomal double-strand breaks (DSBs) is necessary for genomic
      integrity in all organisms. Genetic consequences of misrepair include chromosomal
      loss, deletion, and duplication resulting in loss of heterozygosity (LOH), a
      common finding in human solid tumors. Although work with radiation-sensitive cell
      lines suggests that mammalian cells primarily rejoin DSBs by nonhomologous
      mechanisms, alternative mechanisms that are implicated in chromosomal LOH, such
      as allelic recombination, may also occur. We have examined chromosomal DSB repair
      between homologs in a gene targeted mammalian cell line at the retinoblastoma
      (Rb) locus. We have found that allelic recombinational repair occurs in mammalian
      cells and is increased at least two orders of magnitude by the induction of a
      chromosomal DSB. One consequence of allelic recombination is LOH at the Rb locus.
      Some of the repair events also resulted in other types of genetic instability,
      including deletions and duplications. We speculate that mammalian cells may have
      developed efficient nonhomologous DSB repair processes to bypass allelic
      recombination and the potential for reduction to homozygosity.

PMID- 9256423
TI  - A protein encoded by a group I intron in Aspergillus nidulans directly assists
      RNA splicing and is a DNA endonuclease.
AB  - Some group I introns self-splice in vitro, but almost all are thought to be
      assisted by proteins in vivo. Mutational analysis has shown that the splicing of
      certain group I introns depends upon a maturase protein encoded by the intron
      itself. However the effect of a protein on splicing can be indirect. We now
      provide evidence that a mitochondrial intron-encoded protein from Aspergillus
      nidulans directly facilitates splicing in vitro. This demonstrates that a
      maturase is an RNA splicing protein. The protein-assisted reaction is as fast as
      that of any other known group I intron. Interestingly the protein is also a DNA
      endonuclease, an activity required for intron mobilization. Mobile elements
      frequently encode proteins that promote their propagation. Intron-encoded
      proteins that also assist RNA splicing would facilitate both the transposition
      and horizontal transmission of introns.

PMID- 9256424
TI  - Two-component kinase-like activity of nm23 correlates with its motility
      suppressing activity.
AB  - Nm23 genes, which encode nucleoside diphosphate kinases, have been implicated in
      suppressing tumor metastasis. The motility of human breast carcinoma cells can be
      suppressed by transfection with wild-type nm23-H1, but not by transfections with
      two nm23-H1 mutants, nm23-H1(S12OG) and nm23-H1(P96S). Here we report that nm23
      H1 can transfer a phosphate from its catalytic histidine to aspartate or
      glutamate residues on 43-kDa membrane proteins. One of the 43-kDa membrane
      proteins was not phosphorylated by either nm23-H1(P96S) or nm23-H1(S120G), and
      another was phosphorylated much more slowly by nm23-H1(P96S) and by nm23
      H1(S120G) than by wild-type nm23-H1. Nm23-H1 also can transfer phosphate from its
      catalytic histidine to histidines on ATP-citrate lyase and succinic thiokinase.
      The rates of phosphorylation of ATP-citrate lyase by nm23-H1(S120G) and nm23
      H1(P96S) were similar to that by wild-type nm23-H1. The rate of phosphorylation
      of succinic thiokinase by nm23-H1(S120) was similar to that by wild-type nm23-H1,
      and the rate of phosphorylation of succinic thiokinase by nm23-H1(P96S) was about
      half that by wild-type nm23-H1. Thus, the transfer of phosphate from nm23-H1 to
      aspartates or glutamates on other proteins appears to correlate better with the
      suppression of motility than does the transfer to histidines.

PMID- 9256425
TI  - A role for TFIIH in controlling the activity of early RNA polymerase II
      elongation complexes.
AB  - TFIIH is a multifunctional RNA polymerase II transcription factor that possesses
      DNA-dependent ATPase, DNA helicase, and protein kinase activities. Previous
      studies have established that TFIIH enters the preinitiation complex and fulfills
      a critical role in initiation by catalyzing ATP-dependent formation of the open
      complex prior to synthesis of the first phosphodiester bond of nascent
      transcripts. In this report, we present direct evidence that TFIIH also controls
      RNA polymerase II activity at a postinitiation stage of transcription, by
      preventing premature arrest by very early elongation complexes just prior to
      their transition to stably elongating complexes. Unexpectedly, we observe that
      TFIIH is capable of entering the transcription cycle not only during assembly of
      the preinitiation complex but also after initiation and synthesis of as many as
      four to six phosphodiester bonds. These findings shed new light on the role of
      TFIIH in initiation and promoter escape and reveal an unanticipated flexibility
      in the ability of TFIIH to interact with RNA polymerase II transcription
      intermediates prior to, during, and immediately after initiation.

PMID- 9256426
TI  - Significance of chaperonin 10-mediated inhibition of ATP hydrolysis by chaperonin
      60.
AB  - Chaperonins are essential for the folding of proteins in bacteria, mitochondria,
      and chloroplasts. We have functionally characterized the yeast mitochondrial
      chaperonins hsp60 and hsp10. In the presence of ADP, one molecule of hsp10 binds
      to hsp60 with an apparent Kd of 0.9 nM and a second molecule of hsp10 binds with
      a Kd of 24 nM. In the presence of ATP, the purified yeast chaperonins mediate the
      refolding of mitochondrial malate dehydrogenase. Hsp10 inhibits the ATPase
      activity of hsp60 by about 40%. Hsp10(P36H) is a point mutant of hsp10 that
      confers temperature-sensitive growth to yeast. Consistent with the in vivo
      phenotype, refolding of mitochondrial malate dehydrogenase in the presence of
      purified hsp10(P36H) and hsp60 is reduced at 25 degrees C and abolished at 30
      degrees C. The affinity of hsp10(P36H) to hsp60 as well as to Escherichia coli
      GroEL is reduced. However, this decrease in affinity does not correlate with the
      functional defect, because hsp10(P36H) fully assists the GroEL-mediated refolding
      of malate dehydrogenase at 30 degrees C. Refolding activity, rather, correlates
      with the ability of hsp10(P36H) to inhibit the ATPase of GroEL but not that of
      hsp60. Based on our findings, we propose that the inhibition of ATP hydrolysis is
      mechanistically coupled to chaperonin-mediated protein folding.

PMID- 9256427
TI  - Chymase cleavage of stem cell factor yields a bioactive, soluble product.
AB  - Stem cell factor (SCF) is produced by stromal cells as a membrane-bound molecule,
      which may be proteolytically cleaved at a site close to the membrane to produce a
      soluble bioactive form. The proteases producing this cleavage are unknown. In
      this study, we demonstrate that human mast cell chymase, a chymotrypsin-like
      protease, cleaves SCF at a novel site. Cleavage is at the peptide bond between
      Phe-158 and Met-159, which are encoded by exon 6 of the SCF gene. This cleavage
      results in a soluble bioactive product that is 7 amino acids shorter at the C
      terminus than previously identified soluble SCF. This research shows the
      identification of a physiologically relevant enzyme that specifically cleaves
      SCF. Because mast cells express the KIT protein, the receptor for SCF, and
      respond to SCF by proliferation and degranulation, this observation identifies a
      possible feedback loop in which chymase released from mast cell secretory
      granules may solubilize SCF bound to the membrane of surrounding stromal cells.
      The liberated soluble SCF may in turn stimulate mast cell proliferation and
      differentiated functions; this loop could contribute to abnormal accumulations of
      mast cells in the skin and hyperpigmentation at sites of chronic cutaneous
      inflammation.

PMID- 9256428
TI  - Structural kinetics of transcription activation at the malT promoter of
      Escherichia coli by UV laser footprinting.
AB  - We have studied the kinetics of transcriptional initiation and activation at the
      malT and malTp1 promoters of Escherichia coli using UV laser footprinting.
      Contrary to previous studies and because of the very rapid signal acquisition by
      this technique, we can obtain structural information about true reaction
      intermediates of transcription initiation. The consequences of adding a
      transcriptional activator, the cAMP receptor protein/cAMP complex (CRP), are
      monitored in real time, permitting us to assign specific interactions to the
      activation of discrete steps in transcription initiation. Direct protein-protein
      contacts between CRP and the RNA polymerase appeared very rapidly, followed by
      DNA melting around the -10 hexamer. CRP slightly increased the rate of this
      isomerization reaction but, more importantly, favored the establishment of
      additional contacts between the DNA upstream of the CRP binding site and RNA
      polymerase subsequent to open complex formation. These contacts make a major
      contribution to transcriptional activation by stabilizing open forms of the
      promoter complex, thereby indirectly accelerating promoter escape. The ensemble
      of the kinetic, structural signals demonstrated directly that CRP exerts most of
      its activating effects on the late stages of transcriptional initiation at the
      malT promoter.

PMID- 9256430
TI  - Chromatin assembly in a yeast whole-cell extract.
AB  - A simple in vitro system that supports chromatin assembly was developed for
      Saccharomyces cerevisiae. The assembly reaction is ATP-dependent, uses soluble
      histones and assembly factors, and generates physiologically spaced nucleosomes.
      We analyze the pathway of histone recruitment into nucleosomes, using this system
      in combination with genetic methods for the manipulation of yeast. This analysis
      supports the model of sequential recruitment of H3/H4 tetramers and H2A/H2B
      dimers into nucleosomes. Using a similar approach, we show that DNA ligase I can
      play an important role in template repair during assembly. These studies
      demonstrate the utility of this system for the combined biochemical and genetic
      analysis of chromatin assembly in yeast.

PMID- 9256429
TI  - SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor
      alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute
      promyelocytic leukemia.
AB  - Retinoic acid receptors (RARs) are hormone-regulated transcription factors that
      control key aspects of normal differentiation. Aberrant RAR activity may be a
      causal factor in neoplasia. Human acute promyelocytic leukemia, for example, is
      tightly linked to chromosomal translocations that fuse novel amino acid sequences
      (denoted PML, PLZF, and NPM) to the DNA-binding and hormone-binding domains of
      RARalpha. The resulting chimeric receptors have unique transcriptional properties
      that may contribute to leukemogenesis. Normal RARs repress gene transcription by
      associating with ancillary factors denoted corepressors (also referred to as
      SMRT, N-CoR, TRAC, or RIP13). We report here that the PML-RARalpha and PLZF
      RARalpha oncoproteins retain the ability of RARalpha to associate with
      corepressors, and that this corepressor association correlates with certain
      aspects of the leukemic phenotype. Unexpectedly, the PLZF moiety itself can
      interact with SMRT corepressor. This interaction with corepressor is mediated, in
      part, by a POZ motif within PLZF. Given the presence of POZ motifs in a number of
      known transcriptional repressors, similar interactions with SMRT may play a role
      in transcriptional silencing by a variety of both receptor and nonreceptor
      transcription factors.

PMID- 9256431
TI  - A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma
      protein.
AB  - The retinoblastoma protein (Rb) plays a critical role in cell proliferation,
      differentiation, and development. To decipher the mechanism of Rb function at the
      molecular level, we have systematically characterized a number of Rb-interacting
      proteins, among which is the clone C5 described here, which encodes a protein of
      1,978 amino acids with an estimated molecular mass of 230 kDa. The corresponding
      gene was assigned to chromosome 14q31, the same region where genetic alterations
      have been associated with several abnormalities of thyroid hormone response. The
      protein uses two distinct regions to bind Rb and thyroid hormone receptor (TR),
      respectively, and thus was named Trip230. Trip230 binds to Rb independently of
      thyroid hormone while it forms a complex with TR in a thyroid hormone-dependent
      manner. Ectopic expression of the protein Trip230 in cells, but not a mutant form
      that does not bind to TR, enhances specifically TR-dependent transcriptional
      activity. Coexpression of wild-type Rb, but not mutant Rb that fails to bind to
      Trip230, inhibits such activity. These results not only identify a coactivator
      molecule that modulates TR activity, but also uncover a role for Rb in a pathway
      that responds to thyroid hormone.

PMID- 9256432
TI  - Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent
      translation.
AB  - The yeast translation factor eIF4G associates with both the cap-binding protein
      eIF4E and the poly(A)-binding protein Pab1p. Here we report that the two yeast
      eIF4G homologs, Tif4631p and Tif4632p, share a conserved Pab1p-binding site. This
      site is required for Pab1p and poly(A) tails to stimulate the in vitro
      translation of uncapped polyadenylylated mRNA, and the region encompassing it is
      required for the cap and the poly(A) tail to synergistically stimulate
      translation. This region on Tif4631p becomes essential for cell growth when the
      eIF4E binding site on Tif4631p is mutated. Pab1p mutations also show synthetic
      lethal interactions with eIF4E mutations. These data suggest that eIF4G mediates
      poly(A) tail stimulated translation in vitro, and that Pab1p and the domain
      encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of
      eIF4E function in vivo.

PMID- 9256433
TI  - P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity
      phosphatase.
AB  - Protein tyrosine phosphatases (PTPs) have long been thought to play a role in
      tumor suppression due to their ability to antagonize the growth promoting protein
      tyrosine kinases. Recently, a candidate tumor suppressor from 10q23, termed P
      TEN, was isolated, and sequence homology was demonstrated with members of the PTP
      family, as well as the cytoskeletal protein tensin. Here we show that recombinant
      P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine,
      threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity
      phosphatase. In addition, P-TEN exhibited a high degree of substrate specificity,
      showing selectivity for extremely acidic substrates in vitro. Furthermore, we
      demonstrate that mutations in P-TEN, identified from primary tumors, tumor cells
      lines, and a patient with Bannayan-Zonana syndrome, resulted in the ablation of
      phosphatase activity, demonstrating that enzymatic activity of P-TEN is necessary
      for its ability to function as a tumor suppressor.

PMID- 9256435
TI  - Human argininosuccinate lyase: a structural basis for intragenic complementation.
AB  - Intragenic complementation has been observed at the argininosuccinate lyase (ASL)
      locus. Intragenic complementation is a phenomenon that occurs when a multimeric
      protein is formed from subunits produced by different mutant alleles of a gene.
      The resulting hybrid protein exhibits enzymatic activity that is greater than
      that found in the oligomeric proteins produced by each mutant allele alone. The
      mutations involved in the most successful complementation event observed in ASL
      deficiency were found to be an aspartate to glycine mutation at codon 87 of one
      allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the
      other (Q286R). To understand the structural basis of the Q286R:D87G intragenic
      complementation event at the ASL locus, we have determined the x-ray crystal
      structure of recombinant human ASL at 4. 0 A resolution. The structure has been
      refined to an R factor of 18. 8%. Two monomers related by a noncrystallographic 2
      fold axis comprise the asymmetric unit, and a crystallographic 2-fold axis of
      space group P3121 completes the tetramer. Each of the four active sites is
      composed of residues from three monomers. Structural mapping of the Q286R and
      D87G mutations indicate that both are near the active site and each is
      contributed by a different monomer. Thus when mutant monomers combine randomly
      such that one active site contains both mutations, it is required by molecular
      symmetry that another active site exists with no mutations. These "native" active
      sites give rise to the observed partial recovery of enzymatic activity.

PMID- 9256434
TI  - Primary structure and tissue distribution of two novel proline-rich gamma
      carboxyglutamic acid proteins.
AB  - Two human cDNAs that encode novel vitamin K-dependent proteins have been cloned
      and sequenced. The predicted amino acid sequences suggest that both are single
      pass transmembrane proteins with amino-terminal gamma-carboxyglutamic acid
      containing domains preceded by the typical propeptide sequences required for
      posttranslational gamma-carboxylation of glutamic acid residues. The
      polypeptides, with deduced molecular masses of 23 and 17 kDa, are proline-rich
      within their putative cytoplasmic domains and contain several copies of the
      sequences PPXY and PXXP, motifs found in a variety of signaling and cytoskeletal
      proteins. Accordingly, these two proteins have been called proline-rich Gla
      proteins (PRGP1 and PRGP2). Unlike the gamma-carboxyglutamic acid domain
      containing proteins of the blood coagulation cascade, the two PRGPs are expressed
      in a variety of extrahepatic tissues, with PRGP1 and PRGP2 most abundantly
      expressed in the spinal cord and thyroid, respectively, among those tissues
      tested. Thus, these observations suggest a novel physiological role for these two
      new members of the vitamin K-dependent family of proteins.

PMID- 9256437
TI  - Proof for a nonproteinaceous calcium-selective channel in Escherichia coli by
      total synthesis from (R)-3-hydroxybutanoic acid and inorganic polyphosphate.
AB  - Traditionally, the structure and properties of natural products have been
      determined by total synthesis and comparison with authentic samples. We have now
      applied this procedure to the first nonproteinaceous ion channel, isolated from
      bacterial plasma membranes, and consisting of a complex of poly(3
      hydroxybutyrate) and calcium polyphosphate. To this end, we have now synthesized
      the 128-mer of hydroxybutanoic acid and prepared a complex with inorganic calcium
      polyphosphate (average 65-mer), which was incorporated into a planar lipid
      bilayer of synthetic phospholipids. We herewith present data that demonstrate
      unambiguously that the completely synthetic complex forms channels that are
      indistinguishable in their voltage-dependent conductance, in their selectivity
      for divalent cations, and in their blocking behavior (by La3+) from channels
      isolated from Escherichia coli. The implications of our finding for prebiotic
      chemistry, biochemistry, and biology are discussed.

PMID- 9256436
TI  - Propeptide and glutamate-containing substrates bound to the vitamin K-dependent
      carboxylase convert its vitamin K epoxidase function from an inactive to an
      active state.
AB  - The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the
      posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid in
      precursor proteins containing the gamma-carboxylation recognition site (gamma
      CRS). During this reaction, glutamic acid is converted to gamma-carboxyglutamic
      acid while vitamin KH2 is converted to vitamin K 2,3-epoxide. Recombinant bovine
      carboxylase was purified free of gamma-CRS-containing propeptide and endogenous
      substrate in a single-step immunoaffinity procedure. We show that in the absence
      of gamma-CRS-containing propeptide and/or glutamate-containing substrate,
      carboxylase has little or no epoxidase activity. Epoxidase activity is induced by
      Phe-Leu-Glu-Glu-Leu (FLEEL) (9.2 pmol per min per pmol of enzyme), propeptide,
      residues -18 to -1 of proFactor IX (3.4 pmol per min per pmol of enzyme), FLEEL
      and propeptide (100 pmol per min per pmol of enzyme), and proPT28
      (HVFLAPQQARSLLQRVRRANTFLEEVRK, residues -18 to +10 of human acarboxy
      proprothrombin), (5.3 pmol per min per pmol of enzyme). These results indicate
      that in the absence of propeptide or glutamate-containing substrate, oxygenation
      of vitamin K by the carboxylase does not occur. Upon addition of propeptide or
      glutamate-containing substrate, the enzyme is converted to an active epoxidase.
      This regulatory mechanism prevents the generation of a highly reactive vitamin K
      intermediate in the absence of a substrate for carboxylation.

PMID- 9256438
TI  - Crossover isomer bias is the primary sequence-dependent property of immobilized
      Holliday junctions.
AB  - Recombination of genes is essential to the evolution of genetic diversity, the
      segregation of chromosomes during cell division, and certain DNA repair
      processes. The Holliday junction, a four-arm, four-strand branched DNA crossover
      structure, is formed as a transient intermediate during genetic recombination and
      repair processes in the cell. The recognition and subsequent resolution of
      Holliday junctions into parental or recombined products appear to be critically
      dependent on their three-dimensional structure. Complementary NMR and time
      resolved fluorescence resonance energy transfer experiments on immobilized four
      arm DNA junctions reported here indicate that the Holliday junction cannot be
      viewed as a static structure but rather as an equilibrium mixture of two
      conformational isomers. Furthermore, the distribution between the two possible
      crossover isomers was found to depend on the sequence in a manner that was not
      anticipated on the basis of previous low-resolution experiments.

PMID- 9256440
TI  - Parallel-up structure evidences the molecular directionality during biosynthesis
      of bacterial cellulose.
AB  - The "parallel-up" packing in cellulose Ialpha and Ibeta unit cells was
      experimentally demonstrated by a combination of direct-staining the reducing ends
      of cellulose chains and microdiffraction-tilting electron crystallographic
      analysis. Microdiffraction investigation of nascent bacterial cellulose
      microfibrils showed that the reducing end of the growing cellulose chains points
      away from the bacterium, and this provides direct evidence that polymerization by
      the cellulose synthase takes place at the nonreducing end of the growing
      cellulose chains. This mechanism is likely to be valid also for a number of
      processive glycosyltransferases such as chitin synthases, hyaluronan synthases,
      and proteins involved in the synthesis of nodulation factor backbones.

PMID- 9256439
TI  - The roles of the two proton input channels in cytochrome c oxidase from
      Rhodobacter sphaeroides probed by the effects of site-directed mutations on time
      resolved electrogenic intraprotein proton transfer.
AB  - The crystal structures of cytochrome c oxidase from both bovine and Paracoccus
      denitrificans reveal two putative proton input channels that connect the heme
      copper center, where dioxygen is reduced, to the internal aqueous phase. In this
      work we have examined the role of these two channels, looking at the effects of
      site-directed mutations of residues observed in each of the channels of the
      cytochrome c oxidase from Rhodobacter sphaeroides. A photoelectric technique was
      used to monitor the time-resolved electrogenic proton transfer steps associated
      with the photo-induced reduction of the ferryl-oxo form of heme a3 (Fe4+ = O2-)
      to the oxidized form (Fe3+OH-). This redox step requires the delivery of a
      "chemical" H+ to protonate the reduced oxygen atom and is also coupled to proton
      pumping. It is found that mutations in the K channel (K362M and T359A) have
      virtually no effect on the ferryl-oxo-to-oxidized (F-to-Ox) transition, although
      steady-state turnover is severely limited. In contrast, electrogenic proton
      transfer at this step is strongly suppressed by mutations in the D channel. The
      results strongly suggest that the functional roles of the two channels are not
      the separate delivery of chemical or pumped protons, as proposed recently [Iwata,
      S., Ostermeier, C., Ludwig, B. & Michel, H. (1995) Nature (London) 376, 660-669].
      The D channel is likely to be involved in the uptake of both "chemical" and
      "pumped" protons in the F-to-Ox transition, whereas the K channel is probably
      idle at this partial reaction and is likely to be used for loading the enzyme
      with protons at some earlier steps of the catalytic cycle. This conclusion agrees
      with different redox states of heme a3 in the K362M and E286Q mutants under
      aerobic steady-state turnover conditions.

PMID- 9256441
TI  - Analysis of the role of the Spitzenkorper in fungal morphogenesis by computer
      simulation of apical branching in Aspergillus niger.
AB  - High-resolution video microscopy, image analysis, and computer simulation were
      used to study the role of the Spitzenkorper (Spk) in apical branching of ramosa
      1, a temperature-sensitive mutant of Aspergillus niger. A shift to the
      restrictive temperature led to a cytoplasmic contraction that destabilized the
      Spk, causing its disappearance. After a short transition period, new Spk appeared
      where the two incipient apical branches emerged. Changes in cell shape, growth
      rate, and Spk position were recorded and transferred to the FUNGUS SIMULATOR
      program to test the hypothesis that the Spk functions as a vesicle supply center
      (VSC). The simulation faithfully duplicated the elongation of the main hypha and
      the two apical branches. Elongating hyphae exhibited the growth pattern described
      by the hyphoid equation. During the transition phase, when no Spk was visible,
      the growth pattern was nonhyphoid, with consecutive periods of isometric and
      asymmetric expansion; the apex became enlarged and blunt before the apical
      branches emerged. Video microscopy images suggested that the branch Spk were
      formed anew by gradual condensation of vesicle clouds. Simulation exercises where
      the VSC was split into two new VSCs failed to produce realistic shapes, thus
      supporting the notion that the branch Spk did not originate by division of the
      original Spk. The best computer simulation of apical branching morphogenesis
      included simulations of the ontogeny of branch Spk via condensation of vesicle
      clouds. This study supports the hypothesis that the Spk plays a major role in
      hyphal morphogenesis by operating as a VSC-i.e., by regulating the traffic of
      wall-building vesicles in the manner predicted by the hyphoid model.

PMID- 9256442
TI  - Defective placental vasculogenesis causes embryonic lethality in VHL-deficient
      mice.
AB  - Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes
      patients to develop von Hippel-Lindau disease, and somatic VHL inactivation is an
      early genetic event leading to the development of sporadic renal cell carcinoma.
      The VHL gene was disrupted by targeted homologous recombination in murine
      embryonic stem cells, and a mouse line containing an inactivated VHL allele was
      generated. While heterozygous VHL (+/-) mice appeared phenotypically normal, VHL 
      /- mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5).
      Homozygous VHL -/- embryos appeared to develop normally until E9.5 to E10.5, when
      placental dysgenesis developed. Embryonic vasculogenesis of the placenta failed
      to occur in VHL -/- mice, and hemorrhagic lesions developed in the placenta.
      Subsequent hemorrhage in VHL -/- embryos caused necrosis and death. These results
      indicate that VHL expression is critical for normal extraembryonic vascular
      development.

PMID- 9256443
TI  - A novel alternate secretory pathway for the export of Plasmodium proteins into
      the host erythrocyte.
AB  - The malarial parasite dramatically alters its host cell by exporting and
      targeting proteins to specific locations within the erythrocyte. Little is known
      about the mechanisms by which the parasite is able to carry out this
      extraparasite transport. The fungal metabolite brefeldin A (BFA) has been used to
      study the secretory pathway in eukaryotes. BFA treatment of infected erythrocytes
      inhibits protein export and results in the accumulation of exported Plasmodium
      proteins into a compartment that is at the parasite periphery. Parasite proteins
      that are normally localized to the erythrocyte membrane, to nonmembrane bound
      inclusions in the erythrocyte cytoplasm, or to the parasitophorous vacuolar
      membrane accumulate in this BFA-induced compartment. A single BFA-induced
      compartment is detected per parasite and the various exported proteins colocalize
      to this compartment regardless of their final destinations. Parasite membrane
      proteins do not accumulate in this novel compartment, but accumulate in the
      endoplasmic reticulum (ER), suggesting that the parasite has two secretory
      pathways. This alternate secretory pathway is established immediately after
      merozoite invasion and at least some dense granule proteins also use the
      alternate pathway. The BFA-induced compartment exhibits properties that are
      similar to the ER, but it is clearly distinct from the ER. We propose to call
      this new organelle the secondary ER of apicomplexa. This ER-like organelle is an
      early, if not the first, step in the export of Plasmodium proteins into the host
      erythrocyte.

PMID- 9256444
TI  - A micromachined device provides a new bend on fibroblast traction forces.
AB  - We have measured the traction forces generated by fibroblasts using a novel
      micromachined device that is capable of determining the subcellular forces
      generated by individual adhesive contacts. The front of migrating fibroblasts
      produced intermittent rearward forces whereas the tail produced larger forward
      directed forces. None of the forces were steady; they all had periodic
      fluctuations. The transition between forward and rearward traction forces
      occurred at the nucleus, not at the rear of the cell or the border between the
      endoplasm and the ectoplasm. We propose that the coupling of lamella extensions
      to fluctuating rearward tractions in front of the nuclear region move the front
      of a fibroblast forward, while force-facilitated release of rear adhesive
      contacts and anterior-directed tractions allow the region behind the nucleus to
      advance.

PMID- 9256445
TI  - mRNA binding protein mrnp 41 localizes to both nucleus and cytoplasm.
AB  - We have identified and molecularly characterized a human protein with a Mr of
      40,880 Da. After UV irradiation of HeLa cells, this protein was cross-linked to
      poly(A)-containing mRNA and was therefore designated mrnp 41 (for mRNA binding
      protein of 41 kDa). Cell fractionation and immunoblotting showed mrnp 41 in both
      the cytoplasm and the nucleus and particularly in the nuclear envelope.
      Immunofluorescence microscopy localized mrnp 41 to distinct foci in the
      nucleoplasm, to the nuclear rim, and to meshwork-like structures throughout the
      cytoplasm. The cytoplasmic meshwork staining was disrupted by prior treatment of
      cells with the actin filament- or microtubule-disrupting drugs cytochalasin or
      nocodazole, respectively, suggesting association of mrnp 41 with the
      cytoskeleton. Double immunofluorescence with antibodies against mrnp 41 and the
      cytoplasmic poly(A) binding protein showed colocalization to the cytoplasmic
      meshwork. Immunogold electronmicroscopy confirmed mrnp 41's cytoplasmic and
      nucleoplasmic localization and revealed a striking labeling of nuclear pore
      complexes. Together these data suggest that mrnp 41 may function in nuclear
      export of mRNPs and/or in cytoplasmic transport on, or attachment to, the
      cytoskeleton. Consistent with a role of mrnp 41 in nuclear export are previous
      reports that mutations in homologs of mrnp 41 in Schizosaccharomyces pombe,
      designated Rae1p, or in Saccharomyces cerevisiae, designated Gle2p, result in
      mRNA accumulation in the nucleus although it is presently not known whether these
      homologs are mRNA binding proteins as well.

PMID- 9256446
TI  - Subtraction hybridization identifies a transformation progression-associated gene
      PEG-3 with sequence homology to a growth arrest and DNA damage-inducible gene.
AB  - Cancer is a progressive multigenic disorder characterized by defined changes in
      the transformed phenotype that culminates in metastatic disease. Determining the
      molecular basis of progression should lead to new opportunities for improved
      diagnostic and therapeutic modalities. Through the use of subtraction
      hybridization, a gene associated with transformation progression in virus- and
      oncogene-transformed rat embryo cells, progression elevated gene-3 (PEG-3), has
      been cloned. PEG-3 shares significant nucleotide and amino acid sequence homology
      with the hamster growth arrest and DNA damage-inducible gene gadd34 and a
      homologous murine gene, MyD116, that is induced during induction of terminal
      differentiation by interleukin-6 in murine myeloid leukemia cells. PEG-3
      expression is elevated in rodent cells displaying a progressed-transformed
      phenotype and in rodent cells transformed by various oncogenes, including Ha-ras,
      v-src, mutant type 5 adenovirus (Ad5), and human papilloma virus type 18. The PEG
      3 gene is transcriptionally activated in rodent cells, as is gadd34 and MyD116,
      after treatment with DNA damaging agents, including methyl methanesulfonate and
      gamma-irradiation. In contrast, only PEG-3 is transcriptionally active in rodent
      cells displaying a progressed phenotype. Although transfection of PEG-3 into
      normal and Ad5-transformed cells only marginally suppresses colony formation,
      stable overexpression of PEG-3 in Ad5-transformed rat embryo cells elicits the
      progression phenotype. These results indicate that PEG-3 is a new member of the
      gadd and MyD gene family with similar yet distinct properties and this gene may
      directly contribute to the transformation progression phenotype. Moreover, these
      studies support the hypothesis that constitutive expression of a DNA damage
      response may mediate cancer progression.

PMID- 9256447
TI  - Expanding the functional human mitochondrial DNA database by the establishment of
      primate xenomitochondrial cybrids.
AB  - The nuclear and mitochondrial genomes coevolve to optimize approximately 100
      different interactions necessary for an efficient ATP-generating system. This
      coevolution led to a species-specific compatibility between these genomes. We
      introduced mitochondrial DNA (mtDNA) from different primates into mtDNA-less
      human cells and selected for growth of cells with a functional oxidative
      phosphorylation system. mtDNA from common chimpanzee, pigmy chimpanzee, and
      gorilla were able to restore oxidative phosphorylation in the context of a human
      nuclear background, whereas mtDNA from orangutan, and species representative of
      Old-World monkeys, New-World monkeys, and lemurs were not. Oxygen consumption, a
      sensitive index of respiratory function, showed that mtDNA from chimpanzee, pigmy
      chimpanzee, and gorilla replaced the human mtDNA and restored respiration to
      essentially normal levels. Mitochondrial protein synthesis was also unaltered in
      successful "xenomitochondrial cybrids." The abrupt failure of mtDNA from primate
      species that diverged from humans as recently as 8-18 million years ago to
      functionally replace human mtDNA suggests the presence of one or a few mutations
      affecting critical nuclear-mitochondrial genome interactions between these
      species. These cellular systems provide a demonstration of intergenus mtDNA
      transfer, expand more than 20-fold the number of mtDNA polymorphisms that can be
      analyzed in a human nuclear background, and provide a novel model for the study
      of nuclear-mitochondrial interactions.

PMID- 9256448
TI  - The beta subunit of CKII negatively regulates Xenopus oocyte maturation.
AB  - CKII (formerly known as casein kinase II) is a ubiquitously expressed enzyme that
      plays an important role in regulating cell growth and differentiation. The beta
      subunit of CKII (CKIIbeta) is not catalytic but forms heterotetramers with the
      catalytic subunit alpha to generate an alpha2beta2 holoenzyme. In Xenopus
      oocytes, CKIIbeta also associates with another serine/threonine kinase, Mos. As a
      key regulator of meiosis, Mos is necessary and sufficient to initiate oocyte
      maturation. We have previously shown that the binding of CKIIbeta to Mos
      represses Mos-mediated mitogen-activated protein kinase (MAPK) activation and
      that the ectopic expression of CKIIbeta inhibits progesterone-induced Xenopus
      oocyte maturation. We have now used an antisense oligonucleotide technique to
      reduce the endogenous CKIIbeta protein level in Xenopus oocytes, and we find that
      oocytes with a reduced content of CKIIbeta are more sensitive to low doses of
      progesterone and show accelerated MAPK activation and germinal vesicle breakdown.
      Furthermore, ectopic expression of a Mos-binding fragment of CKIIbeta suppressed
      the effect of antisense oligonucleotide. These results suggest that the
      endogenous CKIIbeta normally sets a threshold level for Mos protein, which must
      be exceeded for Mos to activate the MAPK signaling pathway and induce oocyte
      maturation.

PMID- 9256449
TI  - Identification of a new mammalian centrin gene, more closely related to
      Saccharomyces cerevisiae CDC31 gene.
AB  - Among the numerous centrin isoforms identified by two-dimensional gel
      electrophoresis in human cells, an acidic and slow-migrating isoform is
      particularly enriched in a centrosome fraction. We report here that this isoform
      specifically reacts with antibodies raised against Saccharomyces cerevisiae
      Cdc31p and is present, as other centrin isoforms, in the distal lumen of
      centrioles. It is encoded by a new centrin gene, which we propose to name HsCEN3
      (Homo sapiens centrin gene 3). This gene is more closely related to the yeast
      CDC31 gene, and shares less identity with algae centrin than HsCEN1 and HsCEN2. A
      murine CDC31-related gene was also found that shows 98% identity and 100%
      similarity with HsCEN3, demonstrating a higher interspecies conservation than the
      murine centrin gene MmCEN1 (Mus musculus centrin gene 1) with either HsCEN1, or
      HsCEN2. Finally, immunological data suggest that a CDC31-related gene could exist
      in amphibians and echinoderms as well. All together, our data suggest the
      existence of two divergent protein subfamilies in the current centrin family,
      which might be involved in distinct centrosome-associated functions. The possible
      implication of this new mammalian centrin gene in centrosome duplication is
      discussed.

PMID- 9256450
TI  - Modeling the control of DNA replication in fission yeast.
AB  - A central event in the eukaryotic cell cycle is the decision to commence DNA
      replication (S phase). Strict controls normally operate to prevent repeated
      rounds of DNA replication without intervening mitoses ("endoreplication") or
      initiation of mitosis before DNA is fully replicated ("mitotic catastrophe").
      Some of the genetic interactions involved in these controls have recently been
      identified in yeast. From this evidence we propose a molecular mechanism of
      "Start" control in Schizosaccharomyces pombe. Using established principles of
      biochemical kinetics, we compare the properties of this model in detail with the
      observed behavior of various mutant strains of fission yeast: wee1(-) (size
      control at Start), cdc13Delta and rum1(OP) (endoreplication), and wee1(-)
      rum1Delta (rapid division cycles of diminishing cell size). We discuss essential
      features of the mechanism that are responsible for characteristic properties of
      Start control in fission yeast, to expose our proposal to crucial experimental
      tests.

PMID- 9256451
TI  - Desynchronization of cells on the developmental path triggers the formation of
      spiral waves of cAMP during Dictyostelium aggregation.
AB  - Whereas it is relatively easy to account for the formation of concentric (target)
      waves of cAMP in the course of Dictyostelium discoideum aggregation after
      starvation, the origin of spiral waves remains obscure. We investigate a
      physiologically plausible mechanism for the spontaneous formation of spiral waves
      of cAMP in D. discoideum. The scenario relies on the developmental path
      associated with the continuous changes in the activity of enzymes such as
      adenylate cyclase and phosphodiesterase observed during the hours that follow
      starvation. These changes bring the cells successively from a nonexcitable state
      to an excitable state in which they relay suprathreshold cAMP pulses, and then to
      autonomous oscillations of cAMP, before the system returns to an excitable state.
      By analyzing a model for cAMP signaling based on receptor desensitization, we
      show that the desynchronization of cells on this developmental path triggers the
      formation of fully developed spirals of cAMP. Developmental paths that do not
      correspond to the sequence of dynamic transitions no relay-relay-oscillations
      relay are less able or fail to give rise to the formation of spirals.

PMID- 9256452
TI  - Expression of Sonic hedgehog gene in regenerating newt limb blastemas
      recapitulates that in developing limb buds.
AB  - This study aimed at characterizing the Sonic hedgehog (shh) gene in newt limbs,
      which encodes a signaling molecule of the zone of polarizing activity (ZPA)
      responsible for determining the anterior-posterior axis of the embryonic chicken
      and mouse limbs. The reverse transcription-PCR showed that adult newt
      regenerating limbs express shh genes. In situ hybridization experiments
      demonstrated that shh genes were expressed in mesenchymal cells of the posterior
      region of both embryonic buds and regenerating blastemas of newt limbs, strongly
      suggesting the presence of ZPA in these tissues. Experiments of the axial
      reversal graft of blastemas further supported this suggestion. The grafted
      blastemas regenerated supernumerary limbs, and this has been explained by three
      models: the polar coordinate model, the boundary model, and the polarizing zone
      model. In favor of the third model, the shh gene was expressed not only in the
      original region (new anterior region) of the graft, but also ectopically in the
      other region (new posterior region) of the same graft. This study implies that
      the regenerating limb blastema produces ZPA as the signaling center of the AP
      patterning as in the developing limb bud and, therefore, supports the notion that
      the limb regeneration recapitulates the limb development.

PMID- 9256453
TI  - CENP-E is an essential kinetochore motor in maturing oocytes and is masked during
      mos-dependent, cell cycle arrest at metaphase II.
AB  - CENP-E, a kinesin-like protein that is known to associate with kinetochores
      during all phases of mitotic chromosome movement, is shown here to be a component
      of meiotic kinetochores as well. CENP-E is detected at kinetochores during
      metaphase I in both mice and frogs, and, as in mitosis, is relocalized to the
      midbody during telophase. CENP-E function is essential for meiosis I because
      injection of an antibody to CENP-E into mouse oocytes in prophase completely
      prevented progression of those oocytes past metaphase I. Beyond this, CENP-E is
      modified or masked during the natural, Mos-dependent, cell cycle arrest that
      occurs at metaphase II, although it is readily detectable at the kinetochores in
      metaphase II oocytes derived from mos-deficient (MOS-/-) mice that fail to arrest
      at metaphase II. This must reflect a masking of some CENP-E epitopes, not the
      absence of CENP-E, in meiosis II because a different polyclonal antibody raised
      to the tail of CENP-E detects CENP-E at kinetochores of metaphase II-arrested
      eggs and because CENP-E reappears in telophase of mouse oocytes activated in the
      absence of protein synthesis.

PMID- 9256457
TI  - East Gondwana ancestry of the sunflower alliance of families.
AB  - The sunflower alliance of families comprises nearly 10% of all flowering plant
      species and includes the largest of all plant families, the sunflower family
      Asteraceae, which has 23,000 species, and the bellflower family Campanulaceae.
      Both are worldwide in distribution, but the majority of their species occur in
      the northern hemisphere. Recently it has been shown that a number of small, woody
      families from the Australian-Southwest Pacific area also belong in this
      relationship. Here we add yet another such family and present phylogenetic,
      biogeographic, and chronological analyses elucidating the origin of this large
      group of plants. We show that the ancestral lineages are confined to Malesia,
      Australia, New Guinea, and New Zealand and that the sunflower and bellflower
      families represent phylogenetically derived lineages within a larger group with a
      Cretaceous and southern-hemisphere, presumably East Gondwana, ancestry. Their
      highly derived position in the flowering plant phylogeny makes this significant
      for understanding the evolution of flowering plants in general.

PMID- 9256456
TI  - Molecular evolution of integrins: genes encoding integrin beta subunits from a
      coral and a sponge.
AB  - The integrin family of cell surface receptors is strongly conserved in higher
      animals, but the evolutionary history of integrins is obscure. We have identified
      and sequenced cDNAs encoding integrin beta subunits from a coral (phylum
      Cnidaria) and a sponge (Porifera), indicating that these proteins existed in the
      earliest stages of metazoan evolution. The coral betaCn1 and, especially, the
      sponge betaPo1 sequences are the most divergent of the "beta1-class" integrins
      and share a number of features not found in any other vertebrate or invertebrate
      integrins. Perhaps the greatest difference from other beta subunits is found in
      the third and fourth repeats of the cysteine-rich stalk, where the generally
      conserved spacings between cysteines are highly variable, but not similar, in
      betaCn1 and betaPo1. Alternatively spliced cDNAs, containing a stop codon about
      midway through the full-length translated sequence, were isolated from the sponge
      library. These cDNAs appear to define a boundary between functional domains, as
      they would encode a protein that includes the globular ligand-binding head but
      would be missing the stalk, transmembrane, and cytoplasmic domains. These and
      other sequence comparisons with vertebrate integrins are discussed with respect
      to models of integrin structure and function.

PMID- 9256458
TI  - Typing of urinary JC virus DNA offers a novel means of tracing human migrations.
AB  - Although polyomavirus JC (JCV) is the proven pathogen of progressive multifocal
      leukoencephalopathy, the fatal demyelinating disease, this virus is ubiquitous as
      a usually harmless symbiote among human beings. JCV propagates in the adult
      kidney and excretes its progeny in urine, from which JCV DNA can readily be
      recovered. The main mode of transmission of JCV is from parents to children
      through long cohabitation. In this study, we collected a substantial number of
      urine samples from native inhabitants of 34 countries in Europe, Africa, and
      Asia. A 610-bp segment of JCV DNA was amplified from each urine sample, and its
      DNA sequence was determined. A worldwide phylogenetic tree subsequently
      constructed revealed the presence of nine subtypes including minor ones. Five
      subtypes (EU, Af2, B1, SC, and CY) occupied rather large territories that
      overlapped with each other at their boundaries. The entire Europe, northern
      Africa, and western Asia were the domain of EU, whereas the domain of Af2
      included nearly all of Africa and southwestern Asia all the way to the
      northeastern edge of India. Partially overlapping domains in Asia were occupied
      by subtypes B1, SC, and CY. Of particular interest was the recovery of JCV
      subtypes in a pocket or pockets that were separated by great geographic distances
      from the main domains of those subtypes. Certain of these pockets can readily be
      explained by recent migrations of human populations carrying these subtypes.
      Overall, it appears that JCV genotyping promises to reveal previously unknown
      human migration routes: ancient as well as recent.

PMID- 9256459
TI  - Detecting immigration by using multilocus genotypes.
AB  - Immigration is an important force shaping the social structure, evolution, and
      genetics of populations. A statistical method is presented that uses multilocus
      genotypes to identify individuals who are immigrants, or have recent immigrant
      ancestry. The method is appropriate for use with allozymes, microsatellites, or
      restriction fragment length polymorphisms (RFLPs) and assumes linkage equilibrium
      among loci. Potential applications include studies of dispersal among natural
      populations of animals and plants, human evolutionary studies, and typing zoo
      animals of unknown origin (for use in captive breeding programs). The method is
      illustrated by analyzing RFLP genotypes in samples of humans from Australian,
      Japanese, New Guinean, and Senegalese populations. The test has power to detect
      immigrant ancestors, for these data, up to two generations in the past even
      though the overall differentiation of allele frequencies among populations is
      low.

PMID- 9256460
TI  - The catalytic subunit of yeast telomerase.
AB  - Telomerase is an RNA-directed DNA polymerase, composed of RNA and protein
      subunits, that replicates the telomere ends of linear eukaryotic chromosomes.
      Using a genetic strategy described here, we identify the product of the EST2
      gene, Est2p, as a subunit of telomerase in the yeast Saccharomyces cerevisiae.
      Est2p is required for enzyme catalysis, as mutations in EST2 were found to result
      in the absence of telomerase activity. Immunochemical experiments show that Est2p
      is an integral subunit of the telomerase enzyme. Critical catalytic residues
      present in RNA-directed DNA polymerases are conserved in Est2p; mutation of one
      such residue abolishes telomerase activity, suggesting a direct catalytic role
      for Est2p.

PMID- 9256461
TI  - Translational coupling by modulation of feedback repression in the IF3 operon of
      Escherichia coli.
AB  - A pseudoknot formed by a long-range interaction in the mRNA of the initiation
      factor 3 (IF3) operon is involved in the translational repression of the gene
      encoding ribosomal protein L35 by another ribosomal protein, L20. The nucleotides
      forming the 5' strand of the key stem of the pseudoknot are located within the
      gene for IF3, whereas those forming the 3' strand are located 280 nt downstream,
      immediately upstream of the Shine-Dalgarno sequence of the gene for L35. Here we
      show that premature termination of IF3 translation at a nonsense codon introduced
      upstream of the pseudoknot results in a substantial enhancement of L20-mediated
      repression of L35 expression. Conversely, an increase of IF3 translation
      decreases repression. These results, in addition to an analysis of the effect of
      mutations in sequences forming the pseudoknot, indicate that IF3 translation
      decreases L20-mediated repression of L35 expression. We propose that ribosomes
      translating IF3 disrupt the pseudoknot and thereby attenuate repression. The
      result is a novel type of translational coupling, where unfolding of the
      pseudoknot by ribosomes translating IF3 does not increase expression of L35
      directly, but alleviates its repression by L20.

PMID- 9256463
TI  - Identification of genes required for Drosophila eye development using a
      phenotypic enhancer-trap.
AB  - A novel method of P-element mutagenesis is described for the isolation of mutants
      affecting the development of the Drosophila compound eye. It exploits the
      interaction between the Bride of Sevenless (Boss) ligand and the Sevenless (Sev)
      receptor tyrosine kinase that triggers the formation of the UV-sensitive
      photoreceptor neuron, R7. Transposition of a boss cDNA transgene, in an otherwise
      boss mutant background, was used as a "phenotypic trap" in live flies to identify
      enhancers expressed during a narrow time window in eye development. Using a rapid
      behavioral screen, more than 400,000 flies were tested for restoration of R7.
      Some 1,800 R7-containing flies were identified. Among these, 21 independent
      insertions with expression of the boss reporter gene in the R8 cell were
      identified by a external eye morphology and staining with an antibody against
      Boss. Among 900 lines with expression of the boss reporter gene in multiple cells
      assessed for homozygous mutant phenotypes, insertions in the marbles, glass,
      gap1, and fasciclin II genes were isolated. This phenotypic enhancer-trap
      facilitates (i) the isolation of enhancer-traps with a specific expression
      pattern, and (ii) the recovery of mutants disrupting development of specific
      tissues. Because the temporal and tissue specificity of the phenotypic trap is
      dependent on the choice of the marker used, this approach can be extended to
      other tissues and developmental stages.

PMID- 9256462
TI  - Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand
      break-induced recombination.
AB  - When gene conversion is initiated by a double-strand break (DSB), any
      nonhomologous DNA that may be present at the ends must be removed before new DNA
      synthesis can be initiated. In Saccharomyces cerevisiae, removal of nonhomologous
      ends depends not only on the nucleotide excision repair endonuclease Rad1/Rad10
      but also on Msh2 and Msh3, two proteins that are required to correct mismatched
      bp. These proteins have no effect when DSB ends are homologous to the donor,
      either in the kinetics of recombination or in the proportion of gene conversions
      associated with crossing-over. A second DSB repair pathway, single-strand
      annealing also requires Rad1/Rad10 and Msh2/Msh3, but reveals a difference in
      their roles. When the flanking homologous regions that anneal are 205 bp, the
      requirement for Msh2/Msh3 is as great as for Rad1/Rad10; but when the annealing
      partners are 1,170 bp, Msh2/Msh3 have little effect, while Rad1/Rad10 are still
      required. Mismatch repair proteins Msh6, Pms1, and Mlh1 are not required. We
      suggest Msh2 and Msh3 recognize not only heteroduplex loops and mismatched bp,
      but also branched DNA structures with a free 3' tail.

PMID- 9256465
TI  - The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities
      in CHO UV40 cells.
AB  - The Chinese hamster ovary (CHO) mutant UV40 cell line is hypersensitive to UV and
      ionizing radiation, simple alkylating agents, and DNA cross-linking agents. The
      mutant cells also have a high level of spontaneous chromosomal aberrations and 3
      fold elevated sister chromatid exchange. We cloned and sequenced a human cDNA,
      designated XRCC9, that partially corrected the hypersensitivity of UV40 to
      mitomycin C, cisplatin, ethyl methanesulfonate, UV, and gamma-radiation. The
      spontaneous chromosomal aberrations in XRCC9 cDNA transformants were almost fully
      corrected whereas sister chromatid exchanges were unchanged. The XRCC9 genomic
      sequence was cloned and mapped to chromosome 9p13. The translated XRCC9 sequence
      of 622 amino acids has no similarity with known proteins. The 2.5-kb XRCC9 mRNA
      seen in the parental cells was undetectable in UV40 cells. The mRNA levels in
      testis were up to 10-fold higher compared with other human tissues and up to 100
      fold higher compared with other baboon tissues. XRCC9 is a candidate tumor
      suppressor gene that might operate in a postreplication repair or a cell cycle
      checkpoint function.

PMID- 9256466
TI  - The mouse pale ear (ep) mutation is the homologue of human Hermansky-Pudlak
      syndrome.
AB  - The recessive mutation at the pale ear (ep) locus on mouse chromosome 19 was
      found to be the homologue of human Hermansky-Pudlak syndrome (HPS). A positional
      cloning strategy using yeast artificial chromosomes spanning the HPS locus was
      used to identify the HPS gene and its murine counterpart. These genes and their
      predicted proteins are highly conserved at the nucleotide and amino acid levels.
      Sequence analysis of the mutant ep gene revealed the insertion of an
      intracisternal A particle element in a protein-coding 3' exon. Here we
      demonstrate that mice with the ep mutation exhibit abnormalities similar to human
      HPS patients in melanosomes and platelet-dense granules. These results establish
      an animal model of HPS and will facilitate biochemical and molecular analyses of
      the functions of this protein in the membranes of specialized intracellular
      organelles.

PMID- 9256467
TI  - Evidence of evolutionary up-regulation of the single active X chromosome in
      mammals based on Clc4 expression levels in Mus spretus and Mus musculus.
AB  - Previous studies have shown that the chloride channel gene Clc4 is X-linked and
      subject to X inactivation in Mus spretus, but that the same gene is autosomal in
      laboratory strains of mice. This exception to the conservation of linkage of the
      X chromosome in one of two interfertile mouse species was exploited to compare
      expression of Clc4 from the X chromosome to that from the autosome. Clc4 was
      found to be highly expressed in brain tissues of both mouse species. Quantitative
      analyses of species-specific expression of Clc4 in brain tissues from mice
      resulting from M. spretus x laboratory strain crosses, demonstrate that each
      autosomal locus has half the level of Clc4 expression as compared with the single
      active X-linked locus. In contrast expression of another chloride channel gene,
      Clc3, which is autosomal in both mouse species is equal between alleles in F1
      animals. There is no evidence of imprinting of the Clc4 autosomal locus. These
      results are consistent with Ohno's hypothesis of an evolutionary requirement for
      a higher expression of genes on the single active X chromosome to maintain
      balance with autosomal gene expression [Ohno, S. (1967) Sex Chromosomes and Sex
      Linked Genes (Springer, Berlin)].

PMID- 9256468
TI  - Screening for imprinted genes by allelic message display: identification of a
      paternally expressed gene impact on mouse chromosome 18.
AB  - A systematic screen termed the allelic message display (AMD) was developed for
      the hunting of imprinted genes. In AMD, differential display PCR is adopted to
      image allelic expression status of multiple polymorphic transcripts in two
      parental mouse strains, reciprocal F1 hybrids and pooled backcross progenies.
      From the displayed patterns, paternally and maternally expressed transcripts can
      be unequivocally identified. The effectiveness of AMD screening was clearly
      demonstrated by the identification of a paternally expressed gene Impact on mouse
      chromosome 18, the predicted product of which belongs to the YCR59c/yigZ
      hypothetical protein family composed of yeast and bacterial proteins with
      currently unknown function. In contrast with previous screening methods
      necessitating positional cloning efforts or generation of parthenogenetic
      embryos, this approach requires nothing particular but appropriately crossed mice
      and can be readily applied to any tissues at various developmental stages. Hence,
      AMD would considerably accelerate the identification of imprinted genes playing
      pivotal roles in mammalian development and the pathogenesis of various diseases.

PMID- 9256469
TI  - Functionality of major histocompatibility complex class II molecules in mice
      doubly deficient for invariant chain and H-2M complexes.
AB  - By combining two previously generated null mutations, Ii degrees and M degrees ,
      we produced mice lacking the invariant chain and H-2M complexes, both required
      for normal cell-surface expression of major histocompatibility complex class II
      molecules loaded with the usual diverse array of peptides. As expected, the
      maturation and transport of class II molecules, their expression at the cell
      surface, and their capacity to present antigens were quite similar for cells from
      Ii degrees M degrees double-mutant mice and from animals carrying just the Ii
      degrees mutation. More surprising were certain features of the CD4(+) T cell
      repertoire selected in Ii degrees M degrees mice: many fewer cells were selected
      than in Ii+M degrees animals, and these had been purged of self-reactive
      specificities, unlike their counterparts in Ii+M degrees animals. These findings
      suggest (i) that the peptides carried by class II molecules on stromal cells
      lacking H-2M complexes may almost all derive from invariant chain and (ii) that H
      2M complexes edit the peptide array displayed on thymic stromal cells in the
      absence of invariant chain, showing that it can edit, in vivo, peptides other
      than CLIP.

PMID- 9256470
TI  - Comparison of fusion phage libraries displaying VH or single-chain Fv antibody
      fragments derived from the antibody repertoire of a vaccinated melanoma patient
      as a source of melanoma-specific targeting molecules.
AB  - A single-chain Fv (scFv) fusion phage library derived from random combinations of
      VH and VL (variable heavy and light chains) domains in the antibody repertoire of
      a vaccinated melanoma patient was previously used to isolate clones that bind
      specifically to melanoma cells. An unexpected finding was that one of the clones
      encoded a truncated scFv molecule with most of the VL domain deleted, indicating
      that a VH domain alone can exhibit tumor-specific binding. In this report a VH
      fusion phage library containing VH domains unassociated with VL domains was
      compared with a scFv fusion phage library as a source of melanoma-specific
      clones; both libraries contained the same VH domains from the vaccinated melanoma
      patient. The results demonstrate that the clones can be isolated from both
      libraries, and that both libraries should be used to optimize the chance of
      isolating clones binding to different epitopes. Although this strategy has been
      tested only for melanoma, it is also applicable to other cancers. Because of
      their small size, human origin and specificity for cell surface tumor antigens,
      the VH and scFv molecules have significant advantages as tumor-targeting
      molecules for diagnostic and therapeutic procedures and can also serve as probes
      for identifying the cognate tumor antigens.

PMID- 9256471
TI  - Self-antigen does not accelerate immature B cell apoptosis, but stimulates
      receptor editing as a consequence of developmental arrest.
AB  - In pre-B lymphocytes, productive rearrangement of Ig light chain genes allows
      assembly of the B cell receptor (BCR), which selectively promotes further
      developmental maturation through poorly defined transmembrane signaling events.
      Using a novel in vitro system to study immune tolerance during development, we
      find that BCR reactivity to auto-antigen blocks this positive selection,
      preventing down-regulation of light chain gene recombination and promoting
      secondary light chain gene rearrangements that often alter BCR specificity, a
      process called receptor editing. Under these experimental conditions, self
      antigen induces secondary light chain gene rearrangements in at least two-thirds
      of autoreactive immature B cells, but fails to accelerate cell death at this
      stage. These data suggest that in these cells the mechanism of immune tolerance
      is receptor selection rather than clonal selection.

PMID- 9256472
TI  - Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein.
AB  - CTLA-4 plays a critical role in regulating the immune response. It is mainly
      located in cytoplasmic vesicles and is expressed only transiently on the surface
      after T cell activation. In this study, we demonstrate that CTLA-4 is associated
      with AP50, the medium chain of the clathrin-associated coated pit adaptor protein
      complex AP2. In a yeast two-hybrid screen, three individual cDNA clones that
      encode mouse AP50 were isolated, all of which can interact specifically with the
      cytoplasmic domain of mouse CTLA-4, but not with the cytoplasmic domain of mouse
      CD28. We have shown that CTLA-4 can bind specifically to AP50 when CTLA-4 and
      AP50 are cotransfected into human 293T cells. A Y201 to F201 mutation in the YVKM
      intracellular localization motif of the CTLA-4 cytoplasmic domain significantly
      diminished its binding to AP50. We also found that AP50 bound to a CTLA-4 peptide
      containing unphosphorylated Y201 but not to a peptide containing phosphorylated
      Y201. Conversely, the p85 subunit of phosphatidylinositol 3-kinase and, to a
      lesser extent, protein tyrosine phosphatase SYP (SHP-2) and SHP (SHP-1) bind only
      to the CTLA-4 peptide containing phosphorylated Y201. Therefore, the
      phosphorylation status of Y201 in the CTLA-4 cytoplasmic domain determines the
      binding specificity of CTLA-4. These results suggest that AP50 and the coated pit
      adaptor complex AP2 may play an important role in regulating the intracellular
      trafficking and function of CTLA-4.

PMID- 9256473
TI  - A T cell receptor antagonist peptide induces T cells that mediate bystander
      suppression and prevent autoimmune encephalomyelitis induced with multiple myelin
      antigens.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid
      protein (PLP) residues 139-151 (HSLGKWLGHPDKF) can be prevented by treatment with
      a T cell receptor (TCR) antagonist peptide (L144/R147) generated by substituting
      at the two principal TCR contact residues in the encephalitogenic peptide. The
      TCR antagonist peptide blocks activation of encephalitogenic Th1 helper cells in
      vitro, but the mechanisms by which the antagonist peptide blocks EAE in vivo are
      not clear. Immunization with L144/R147 did not inhibit generation of PLP-(139
      151)-specific T cells in vivo. Furthermore, preimmunization with L144/R147
      protected mice from EAE induced with the encephalitogenic peptides PLP-(178-191)
      and myelin oligodendrocyte protein (MOG) residues 92-106 and with mouse myelin
      basic protein (MBP). These data suggest that the L144/R147 peptide does not act
      as an antagonist in vivo but mediates bystander suppression, probably by the
      generation of regulatory T cells. To confirm this we generated T cell lines and
      clones from animals immunized with PLP-(139-151) plus L144/R147. T cells specific
      for L144/R147 peptide were crossreactive with the native PLP-(139-151) peptide,
      produced Th2/Th0 cytokines, and suppressed EAE upon adoptive transfer. These
      studies demonstrate that TCR antagonist peptides may have multiple biological
      effects in vivo. One of the principal mechanisms by which these peptides inhibit
      autoimmunity is by the induction of regulatory T cells, leading to bystander
      suppression of EAE. These results have important implications for the treatment
      of autoimmune diseases where there are autopathogenic responses to multiple
      antigens in the target organ.

PMID- 9256474
TI  - Recombinant human granzyme A binds to two putative HLA-associated proteins and
      cleaves one of them.
AB  - The release of cytotoxic granule contents by cytotoxic T lymphocytes triggers
      apoptotic target cell death. Cytotoxic granules contain a pore-forming protein,
      perforin, and a group of serine proteases called granzymes. We expressed human
      granzyme A in bacteria as a proenzyme capable of in vitro activation by
      enterokinase. The recombinant activated enzyme has catalytic activity against
      substrates with Arg, preferably, or Lys at the P1 position, comparable to
      trypsin. An enzymatically inactive recombinant granzyme A, with the active site
      Ser mutated to Ala, was produced and used with affinity chromatography to
      identify potential substrates. Two granzyme A-binding cytoplasmic proteins of
      molecular mass 33 and 44 kDa were isolated and identified by tryptic fragment
      sequencing as PHAP I and II, ubiquitous putative HLA-associated proteins,
      previously coisolated by binding to an HLA class II peptide. PHAP II forms an SDS
      stable complex with recombinant mutant granzyme A and coprecipitates with it from
      cytoplasmic extracts. PHAP II, either purified or in cell lysates, is cleaved by
      the recombinant enzyme at nanomolar concentrations to a 25-kDa fragment. PHAP II
      begins to be degraded within minutes of initiation of cytotoxic T lymphocyte
      attack. PHAP I and II are candidate participants in the granzyme A pathway of
      cell-mediated cytotoxicity.

PMID- 9256475
TI  - Precursor B cells for autoantibody production in genomically Fas-intact
      autoimmune disease are not subject to Fas-mediated immune elimination.
AB  - The Fas/Fas ligand (FasL) system participates in regulation of the immune system
      through the apoptotic process. However, the extent to which abnormalities in this
      system are involved in the loss of self-tolerance and development of autoimmune
      disease not associated with Fas/FasL mutations remains unknown. The present study
      addresses this issue in Fas/FasL-intact, systemic lupus erythematosus (SLE)-prone
      (NZB x NZW) (NZB/W) F1 mice. While splenic B cells from 2-month-old mice before
      overt SLE expressed Fas poorly, in vitro stimulation with an agonistic anti-CD40
      mAb up-regulated their Fas expression, thus revealing the existence of two
      populations: one was Fashigh and highly susceptible to anti-Fas mAb-induced
      apoptosis, and the other was Faslow and apoptosis-resistant. The Faslow cells
      were included in the CD5(+) B cell subpopulation and contained most of the cells
      that produced IgM anti-DNA antibodies. The isotype of anti-DNA antibodies
      switches from IgM to IgG in NZB/W F1 mice at ages beginning at about 6 months.
      These IgG anti-DNA antibodies were produced almost exclusively by a subpopulation
      of splenic B cells that spontaneously expressed low levels of Fas in vivo and
      were apoptosis-resistant. The findings indicate that precursor B cells for
      autoantibody production and presumably autoantibody-secreting cells in these mice
      are relatively resistant to Fas-mediated apoptosis, a finding supporting the
      concept that abnormalities of Fas-mediated apoptotic process are involved in the
      development of autoreactive B cells in Fas/FasL-intact autoimmune disease.

PMID- 9256476
TI  - Thymocyte development is normal in CTLA-4-deficient mice.
AB  - Recent studies indicate that CTLA-4 interaction with B7 ligands transduces an
      inhibitory signal to T lymphocytes. Mice homozygous for a null mutation in CTLA-4
      have provided the most dramatic example of the functional importance of CTLA-4 in
      vivo. These animals develop a fatal lymphoproliferative disorder and were
      reported to have an increase in CD4(+) and CD8(+) thymocytes and CD4(-)CD8(-)
      thymocytes, and a decrease in CD4(+)CD8(+) thymocytes. Based on these
      observations, it was proposed that CTLA-4 is necessary for normal thymocyte
      development. In this study, CTLA-4-deficient mice carrying an insertional
      mutation into exon 3 of the ctla-4 gene were generated. Although these mice
      display a lymphoproliferative disorder similar to previous reports, there was no
      alteration in the thymocyte profiles when the parathymic lymph nodes were
      excluded from the thymi. Further, thymocyte development was normal throughout
      ontogeny and in neonates, and there was no increase in thymocyte production.
      Finally, T cell antigen receptor signaling, as assessed by proximal and distal
      events, was not altered in thymocytes from CTLA-4(-/-) animals. Collectively,
      these results clearly demonstrate that the abnormal T cell expansion in the CTLA
      4-deficient mice is not due to altered thymocyte development and suggest that the
      apparent altered thymic phenotype previously described was due to the inclusion
      of parathymic lymph nodes and, in visibly ill animals, to the infiltration of the
      thymus by activated peripheral T cells. Thus it appears that CTLA-4 is primarily
      involved in the regulation of peripheral T cell activation.

PMID- 9256477
TI  - Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient
      mice.
AB  - The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) alpha and
      LTbeta form heterotrimers that are expressed on the surface of activated
      lymphocytes and natural killer cells; LTalpha homotrimers can be secreted as
      well. Mice with a disrupted LTalpha gene lack lymph nodes (LN), Peyer's patches
      (PP), and follicular dendritic cell (FDC) networks and reveal profound defects of
      the splenic architecture. However, it is unclear which of these abnormalities is
      the result of the absence in LTalpha homotrimers or LTalphabeta heterotrimers. To
      distinguish between these two possibilities, a mouse strain deficient in LTbeta
      was created employing Cre/loxP-mediated gene targeting. Mice deficient in LTbeta
      reveal severe defects in organogenesis of the lymphoid system similar to those of
      LTalpha-/- mice, except that mesenteric and cervical LN are present in most
      LTbeta-deficient mice. Both LTbeta- and LTalpha-deficient mice show significant
      lymphocytosis in the circulation and peritoneal cavity and lymphocytic
      infiltrations in lungs and liver. After immunization, PNA-positive B cell
      clusters were detected in the splenic white pulp of LTbeta-deficient mice, but
      FDC networks were severely underdeveloped. Collectively, these results indicate
      that LTalpha can signal independently from LTbeta in the formation of PNA
      positive foci in the spleen, and especially in the development of mesenteric and
      cervical LN.

PMID- 9256478
TI  - Potential roles of osteopontin and alphaVbeta3 integrin in the development of
      coronary artery restenosis after angioplasty.
AB  - Angioplasty procedures are increasingly used to reestablish blood flow in blocked
      atherosclerotic coronary arteries. A serious complication of these procedures is
      reocclusion (restenosis), which occurs in 30-50% of patients. Migration of
      coronary artery smooth muscle cells (CASMCs) to the site of injury caused by
      angioplasty and subsequent proliferation are suggested mechanisms of reocclusion.
      Using both cultured human CASMCs and coronary atherectomy tissues, we studied the
      roles of osteopontin (OPN) and one of its receptors, alphavbeta3 integrin, in the
      pathogenesis of coronary restenosis. We also measured the plasma levels of OPN
      before and after angioplasty and determined the effect of exogenous OPN on CASMC
      migration, extracellular matrix invasion, and proliferation. We found that
      cultured CASMCs during log phase of growth and smooth muscle cell layer of the
      coronary atherosclerotic tissues of patients express both OPN mRNA and protein at
      a significantly elevated level compared with controls. Interestingly, whereas the
      baseline plasma OPN levels in control samples were virtually undetectable, those
      in patient plasma were remarkably high. We also found that interaction of OPN
      with alphavbeta3 integrin, expressed on CASMCs, causes migration, extracellular
      matrix invasion, and proliferation. These effects were abolished when OPN or
      alphavbeta3 integrin gene expression in CASMCs was inhibited by specific
      antisense S-oligonucleotide treatment or OPN-alphavbeta3 interaction was blocked
      by treatment of CASMCs with antibodies against OPN or alphavbeta3 integrin. Our
      results demonstrate that OPN and alphavbeta3 integrin play critical roles in
      regulating cellular functions deemed essential for restenosis. In addition, these
      results raise the possibility that transient inhibition of OPN gene expression or
      blocking of OPN-alphavbeta3 interaction may provide a therapeutic approach to
      preventing restenosis.

PMID- 9256479
TI  - Vascular MADs: two novel MAD-related genes selectively inducible by flow in human
      vascular endothelium.
AB  - Vascular endothelium is an important transducer and integrator of both humoral
      and biomechanical stimuli within the cardiovascular system. Utilizing a
      differential display approach, we have identified two genes, Smad6 and Smad7,
      encoding members of the MAD-related family of molecules, selectively induced in
      cultured human vascular endothelial cells by steady laminar shear stress, a
      physiologic fluid mechanical stimulus. MAD-related proteins are a recently
      identified family of intracellular proteins that are thought to be essential
      components in the signaling pathways of the serine/threonine kinase receptors of
      the transforming growth factor beta superfamily. Smad6 and Smad7 possess unique
      structural features (compared with previously described MADs), and they can
      physically interact with each other, and, in the case of Smad6, with other known
      human MAD species, in endothelial cells. Transient expression of Smad6 or Smad7
      in vascular endothelial cells inhibits the activation of a transfected reporter
      gene in response to both TGF-beta and fluid mechanical stimulation. Both Smad6
      and Smad7 exhibit a selective pattern of expression in human vascular endothelium
      in vivo as detected by immunohistochemistry and in situ hybridization. Thus,
      Smad6 and Smad7 constitute a novel class of MAD-related proteins, termed vascular
      MADs, that are induced by fluid mechanical forces and can modulate gene
      expression in response to both humoral and biomechanical stimulation in vascular
      endothelium.

PMID- 9256480
TI  - Targeted overexpression of protein kinase C beta2 isoform in myocardium causes
      cardiomyopathy.
AB  - Increased cardiovascular mortality occurs in diabetic patients with or without
      coronary artery disease and is attributed to the presence of diabetic
      cardiomyopathy. One potential mechanism is hyperglycemia that has been reported
      to activate protein kinase C (PKC), preferentially the beta isoform, which has
      been associated with the development of micro- and macrovascular pathologies in
      diabetes mellitus. To establish that the activation of the PKCbeta isoform can
      cause cardiac dysfunctions, we have established lines of transgenic mice with the
      specific overexpression of PKCbeta2 isoform in the myocardium. These mice
      overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by
      mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte
      necrosis, multifocal fibrosis, and decreased left ventricular performance without
      vascular lesions. The severity of the phenotypes exhibited gene dose-dependence.
      Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic
      factor, c-fos, transforming growth factor, and collagens was also observed.
      Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and
      histological improvement. These findings have firmly established that the
      activation of the PKCbeta2 isoform can cause specific cardiac cellular and
      functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.

PMID- 9256481
TI  - Antibodies to several conformation-dependent epitopes of gp120/gp41 inhibit CCR-5
      dependent cell-to-cell fusion mediated by the native envelope glycoprotein of a
      primary macrophage-tropic HIV-1 isolate.
AB  - The beta-chemokine receptor CCR-5 is essential for the efficient entry of primary
      macrophage-tropic HIV-1 isolates into CD4(+) target cells. To study CCR-5
      dependent cell-to-cell fusion, we have developed an assay system based on the
      infection of CD4(+) CCR-5(+) HeLa cells with a Semliki Forest virus recombinant
      expressing the gp120/gp41 envelope (Env) from a primary clade B HIV-1 isolate
      (BX08), or from a laboratory T cell line-adapted strain (LAI). In this system,
      gp120/gp41 of the "nonsyncytium-inducing," primary, macrophage-tropic HIV-1BX08
      isolate, was at least as fusogenic as that of the "syncytium-inducing" HIV-1LAI
      strain. BX08 Env-mediated fusion was inhibited by the beta-chemokines RANTES
      (regulated upon activation, normal T cell expressed and secreted) and macrophage
      inflammatory proteins 1beta (MIP-1beta) and by antibodies to CD4, whereas LAI Env
      mediated fusion was insensitive to these beta-chemokines. In contrast soluble CD4
      significantly reduced LAI, but not BX08 Env-mediated fusion, suggesting that the
      primary isolate Env glycoprotein has a reduced affinity for CD4. The domains in
      gp120/gp41 involved in the interaction with the CD4 and CCR-5 molecules were
      probed using monoclonal antibodies. For the antibodies tested here, the greatest
      inhibition of fusion was observed with those directed to conformation-dependent,
      rather than linear epitopes. Efficient inhibition of fusion was not restricted to
      epitopes in any one domain of gp120/gp41. The assay was sufficiently sensitive to
      distinguish between antibody- and beta-chemokine-mediated fusion inhibition using
      serum samples from patient BX08, suggesting that the system may be useful for
      screening human sera for the presence of biologically significant antibodies.

PMID- 9256482
TI  - Correlates of latent and productive HIV type-1 infection in tonsillar CD4(+) T
      cells.
AB  - Correlates of virus load and characteristics of virus-producing cells in
      tonsillar tissue were investigated. Our results suggest that when less than 1:100
      tonsillar CD4(+) T cells from individuals infected with HIV type-1 (HIV-1)
      contain replication competent provirus, the level of CD4(+) T cells in tonsils is
      comparable to that observed in uninfected individuals. Virus load at or above
      this level was associated with low CD4 cell numbers in tonsillar tissue. Only a
      few percent of all infected T cells in tonsillar tissue were active virus
      producers, with minor differences observed between individuals. Plasma viremia
      was found to correlate with infectious virus load in tonsillar tissue. With less
      than 1:1,000 of CD4 cells in lymphoid tissues being involved in active virus
      production, direct cytopathic effect by HIV-1 on infected CD4 cells is unlikely
      to fully explain the immunodeficiency seen in AIDS.

PMID- 9256483
TI  - Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease
      represent clonal populations of germinal center-derived tumor B cells.
AB  - Among the four subtypes of Hodgkin disease (HD), lymphocyte-predominant (LP) HD
      is now generally considered as a separate entity. The B cell nature of the
      typical Hodgkin and Reed-Sternberg (HRS) cells and their variants (L and H,
      lymphocytic and histiocytic cells) in LP HD has long been suspected, but the
      question of whether these cells represent a true tumor clone is unclear. We
      previously demonstrated clonal Ig gene rearrangements in one case of LP HD. In
      the present study, five cases of LP HD were analyzed by micromanipulation of
      single HRS cells from frozen tissue sections and DNA amplification of rearranged
      Ig heavy chain genes from those cells. Clonal V gene rearrangements harboring
      somatic mutations were detected in each case. In three cases ongoing somatic
      mutation was evident. This shows that HRS cells in LP HD are a clonal tumor
      population derived from germinal center B cells. The pattern of somatic mutation
      indicates that HRS cells in LP HD are selected for antibody expression. This, and
      the presence of ongoing mutation discriminates LP from classical HD.

PMID- 9256484
TI  - Characterization of the antiproliferative signal mediated by the somatostatin
      receptor subtype sst5.
AB  - We investigated cell proliferation modulated by cholecystokinin (CCK) and
      somatostatin analogue RC-160 in CHO cells bearing endogenous CCKA receptors and
      stably transfected by human subtype sst5 somatostatin receptor. CCK stimulated
      cell proliferation of CHO cells. This effect was suppressed by inhibitor of the
      soluble guanylate cyclase, LY 83583, the inhibitor of the cGMP dependent kinases,
      KT 5823, and the inhibitor of mitogen-activated protein (MAP) kinase kinase, PD
      98059. CCK treatment induced an increase of intracellular cGMP concentrations,
      but concomitant addition of LY 83583 virtually suppressed this increase. CCK also
      activated both phosphorylation and activity of p42-MAP kinase; these effects were
      inhibited by KT 5823. All the effects of CCK depended on a pertussis toxin
      dependent G protein. Somatostatin analogue RC-160 inhibited CCK-induced
      stimulation of cell proliferation but it did not potentiate the suppressive
      effect of the inhibitors LY 83583 and KT 5823. RC-160 inhibited both CCK-induced
      intracellular cGMP formation as well as activation of p42-MAP kinase
      phosphorylation and activity. This inhibitory effect was observed at doses of RC
      160 similar to those necessary to occupy the sst5 recombinant receptor and to
      inhibit CCK-induced cell proliferation. We conclude that, in CHO cells, the
      proliferation and the MAP kinase signaling cascade depend on a cGMP-dependent
      pathway. These effects are positively regulated by CCK and negatively influenced
      by RC-160, interacting through CCKA and sst5 receptors, respectively. These
      studies provide a characterization of the antiproliferative signal mediated by
      sst5 receptor.

PMID- 9256485
TI  - Cytokine suppression of protease activation in wild-type p53-dependent and p53
      independent apoptosis.
AB  - M1 myeloid leukemic cells overexpressing wild-type p53 undergo apoptosis. This
      apoptosis can be suppressed by some cytokines, protease inhibitors, and
      antioxidants. We now show that induction of apoptosis by overexpressing wild-type
      p53 is associated with activation of interleukin-1beta-converting enzyme (ICE)
      like proteases, resulting in cleavage of poly(ADP- ribose) polymerase and the
      proenzyme of the ICE-like protease Nedd-2. Activation of these proteases and
      apoptosis were suppressed by the cytokine interleukin 6 or by a combination of
      the cytokine interferon gamma and the antioxidant butylated hydroxyanisole, and
      activation of poly(ADP-ribose) polymerase and apoptosis were suppressed by some
      protease inhibitors. In a clone of M1 cells that did not express p53, vincristine
      or doxorubicin induced protease activation and apoptosis that were not suppressed
      by protease inhibitors, but were suppressed by interleukin 6. In another myeloid
      leukemia (7-M12) doxorubicin also induced protease activation and apoptosis that
      were not suppressed by protease inhibitors, but were suppressed by granulocyte
      macrophage colony-stimulating factor. The results indicate that (i)
      overexpression of wild-type p53 by itself or treatment with cytotoxic compounds
      in wild-type p53-expressing or p53-nonexpressing myeloid leukemic cells is
      associated with activation of ICE-like proteases; (ii) cytokines exert apoptosis
      suppressing functions upstream of protease activation; (iii) the cytotoxic
      compounds induce additional pathways in apoptosis; and (iv) cytokines can also
      suppress these other components of the apoptotic machinery.

PMID- 9256486
TI  - Calpain is a mediator of preservation-reperfusion injury in rat liver
      transplantation.
AB  - Proteases as well as alterations in intracellular calcium have important roles in
      hepatic preservation-reperfusion injury, and increased calpain activity recently
      has been demonstrated in liver allografts. Experiments were designed to evaluate
      (i) hepatic cytosolic calpain activity during different periods of cold ischemia
      (CI), rewarming, or reperfusion, and (ii) effects of inhibition of calpain on
      liver graft function using the isolated perfused rat liver and arterialized
      orthotopic liver transplantation models. Calpain activity was assayed using the
      fluorogenic substrate Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl coumarin (AMC) and
      expressed as mean +/- SD pmol AMC released/min per mg of cytosolic protein.
      Calpain activity rose significantly after 24 hr of CI in University of Wisconsin
      solution and further increased with longer preservation. Activity also increased
      within 30 min of rewarming, peaking at 120 min. Increased durations of CI
      preceding rewarming resulted in significantly higher activity (P < 0.01). Calpain
      activity increased rapidly upon reperfusion and was significantly enhanced by
      previous CI (P < 0.01). Calpain inhibition with Cbz-Val-Phe methyl ester
      significantly decreased aspartate aminotransferase released in the isolated
      perfused rat liver perfusate (P < 0.05). Duration of survival after orthotopic
      liver transplantation using livers cold-preserved for 40 hr was also
      significantly increased (P < 0.05) with calpain inhibitor. In conclusion, calpain
      proteases are activated during each phase of transplantation and are likely to
      play an important role in the mechanisms of preservation-reperfusion injury.

PMID- 9256487
TI  - Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact
      ovarian function: similarity to estrogen deficiency.
AB  - Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due
      to stimulated bone resorption by osteoclasts. During our investigations of the
      pathogenesis of bone loss in estrogen deficiency, we found that OVX selectively
      stimulates B-lymphopoiesis which results in marked accumulation of B220-positive
      pre-B cells in mouse bone marrow. To examine the possible correlation between
      stimulated B-lymphopoiesis and bone loss, 8-week-old female mice were treated
      with interleukin (IL) 7, which stimulates B-lymphopoiesis in bone marrow. We also
      examined bone mass in IL-7 receptor-knockout mice that exhibit marked suppression
      of B-lymphopoiesis in the bone marrow. The increased B-lymphopoiesis induced by
      IL-7 administration resulted in marked bone loss by stimulation of osteoclastic
      bone resorption in mice with intact ovarian function. The changes in both B
      lymphopoiesis and bone mass in IL-7-treated female mice were similar to those in
      age-matched OVX mice. In contrast, the trabecular bone volume of the femur was
      greatly increased in both female and male IL-7 receptor-knockout mice when
      compared with the respective wild-type and heterozygous littermates. These
      results show that the perturbation of B-lymphopoiesis in the bone marrow is
      closely linked to the change in bone mass. We propose here that the increased B
      lymphopoiesis due to estrogen deficiency is involved in the mechanism of
      stimulated bone resorption.

PMID- 9256489
TI  - A maternal diet high in n - 6 polyunsaturated fats alters mammary gland
      development, puberty onset, and breast cancer risk among female rat offspring.
AB  - We hypothesized that feeding pregnant rats with a high-fat diet would increase
      both circulating 17beta-estradiol (E2) levels in the dams and the risk of
      developing carcinogen-induced mammary tumors among their female offspring.
      Pregnant rats were fed isocaloric diets containing 12% or 16% (low fat) or 43% or
      46% (high fat) of calories from corn oil, which primarily contains the n - 6
      polyunsaturated fatty acid (PUFA) linoleic acid, throughout pregnancy. The plasma
      concentrations of E2 were significantly higher in pregnant females fed a high n -
      6 PUFA diet. The female offspring of these rats were fed with a laboratory chow
      from birth onward, and when exposed to 7,12-dimethylbenz(a)anthracene had a
      significantly higher mammary tumor incidence (60% vs. 30%) and shorter latency
      for tumor appearance (11.4 +/- 0.5 weeks vs. 14.2 +/- 0.6 weeks) than the
      offspring of the low-fat mothers. The high-fat offspring also had puberty onset
      at a younger age, and their mammary glands contained significantly higher numbers
      of the epithelial structures that are the targets for malignant transformation.
      Comparable changes in puberty onset, mammary gland morphology, and tumor
      incidence were observed in the offspring of rats treated daily with 20 ng of E2
      during pregnancy. These data, if extrapolated to humans, may explain the link
      among diet, early puberty onset, mammary parenchymal patterns, and breast cancer
      risk, and indicate that an in utero exposure to a diet high in n - 6 PUFA and/or
      estrogenic stimuli may be critical for affecting breast cancer risk.

PMID- 9256488
TI  - A mouse model for X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder with impaired
      beta-oxidation of very long chain fatty acids (VLCFAs) and reduced function of
      peroxisomal very long chain fatty acyl-CoA synthetase (VLCS) that leads to severe
      and progressive neurological disability. The X-ALD gene, identified by positional
      cloning, encodes a peroxisomal membrane protein (adrenoleukodystrophy protein;
      ALDP) that belongs to the ATP binding cassette transporter protein superfamily.
      Mutational analyses and functional studies of the X-ALD gene confirm that it and
      not VLCS is the gene responsible for X-ALD. Its role in the beta-oxidation of
      VLCFAs and its effect on the function of VLCS are unclear. The complex pathology
      of X-ALD and the extreme variability of its clinical phenotypes are also
      unexplained. To facilitate understanding of X-ALD pathophysiology, we developed
      an X-ALD mouse model by gene targeting. The X-ALD mouse exhibits reduced beta
      oxidation of VLCFAs, resulting in significantly elevated levels of saturated
      VLCFAs in total lipids from all tissues measured and in cholesterol esters from
      adrenal glands. Lipid cleft inclusions were observed in adrenocortical cells of X
      ALD mice under the electron microscope. No neurological involvement has been
      detected in X-ALD mice up to 6 months. We conclude that X-ALD mice exhibit
      biochemical defects equivalent to those found in human X-ALD and thus provide an
      experimental system for testing therapeutic intervention.

PMID- 9256490
TI  - Potent, protective anti-HIV immune responses generated by bimodal HIV envelope
      DNA plus protein vaccination.
AB  - It is generally thought that an effective vaccine to prevent HIV-1 infection
      should elicit both strong neutralizing antibody and cytotoxic T lymphocyte
      responses. We recently demonstrated that potent, boostable, long-lived HIV-1
      envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in
      rhesus monkeys using plasmid-encoded HIV-1 env DNA as the immunogen. In the
      present study, we show that the addition of HIV-1 Env protein to this regimen as
      a boosting immunogen generates a high titer neutralizing antibody response in
      this nonhuman primate species. Moreover, we demonstrate in a pilot study that
      immunization with HIV-1 env DNA (multiple doses) followed by a final immunization
      with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB;
      Env protein from parental HIV IIIB) completely protects monkeys from infection
      after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a
      simian immmunodeficiency virusmac backbone (SHIV-HXBc2). The potent immunity and
      protection seen in these pilot experiments suggest that a DNA prime/DNA plus
      protein boost regimen warrants active investigation as a vaccine strategy to
      prevent HIV-1 infection.

PMID- 9256491
TI  - Sequence of a 189-kb segment of the chromosome of Rhodobacter capsulatus SB1003.
AB  - Cosmids from the 1A3-1A10 region of the complete miniset were individually
      subcloned by using the vector M13 mp18. Sequences of each cosmid were assembled
      from about 400 DNA fragments generated from the ends of these phage subclones and
      merged into one 189-kb contig. About 160 ORFs identified by the CodonUse program
      were subjected to similarity searches. The biological functions of 80 ORFs could
      be assigned reliably by using the WIT and Magpie genome investigation tools.
      Eighty percent of these recognizable ORFs were organized in functional clusters,
      which simplified assignment decisions and increased the strength of the
      predictions. A set of 26 genes for cobalamin biosynthesis, genes for
      polyhydroxyalkanoic acid metabolism, DNA replication and recombination, and DNA
      gyrase were among those identified. Most of the ORFs lacking significant
      similarity with reference databases also were grouped. There are two large
      clusters of these ORFs, one located between 45 and 67 kb of the map, and the
      other between 150 and 183 kb. Nine of the loosely identified ORFs (of 15) of the
      first of these clusters match ORFs from phages or transposons. The other cluster
      also has four ORFs of possible phage origin.

PMID- 9256492
TI  - Variations in frequencies of drug resistance in Plasmodium falciparum.
AB  - Continual exposure of malarial parasite populations to different drugs may have
      selected not only for resistance to individual drugs but also for genetic traits
      that favor initiation of resistance to novel unrelated antimalarials. To test
      this hypothesis, different Plasmodium falciparum clones having varying numbers of
      preexisting resistance mechanisms were treated with two new antimalarial agents:
      5-fluoroorotate and atovaquone. All parasite populations were equally susceptible
      in small numbers. However, when large populations of these clones were challenged
      with either of the two compounds, significant variations in frequencies of
      resistance became apparent. On one extreme, clone D6 from West Africa, which was
      sensitive to all traditional antimalarial agents, failed to develop resistance
      under simple nonmutagenic conditions in vitro. In sharp contrast, the Indochina
      clone W2, which was known to be resistant to all traditional antimalarial drugs,
      independently acquired resistance to both new compounds as much as a 1,000 times
      more frequently than D6. Additional clones that were resistant to some (but not
      all) traditional antimalarial agents acquired resistance to atovaquone at high
      frequency, but not to 5-fluoroorotate. These findings were unexpected and
      surprising based on current views of the evolution of drug resistance in P.
      falciparum populations. Such new phenotypes, named accelerated resistance to
      multiple drugs (ARMD), raise important questions about the genetic and
      biochemical mechanisms related to the initiation of drug resistance in malarial
      parasites. Some potential mechanisms underlying ARMD phenotypes have public
      health implications that are ominous.

PMID- 9256493
TI  - Listeria monocytogenes infection of P388D1 macrophages results in a biphasic NF
      kappaB (RelA/p50) activation induced by lipoteichoic acid and bacterial
      phospholipases and mediated by IkappaBalpha and IkappaBbeta degradation.
AB  - As previously reported, Listeria monocytogenes infection of P388D1 macrophages
      results in a rapid induction of NF-kappaB DNA-binding activity. Here we show that
      this induction of NF-kappaB activity occurs in a biphasic mode: first, a
      transient, IkappaBalpha degradation-dependent phase of activity, also induced by
      the nonvirulent species Listeria innocua, which is mediated by binding of the
      bacteria to the macrophage, or by adding Listeria-derived lipoteichoic acid to
      the macrophage; the second persistent phase of activation is only markedly
      induced when the bacteria enter the cytoplasm of the host cell and express the
      virulence genes plcA and plcB, encoding two phospholipases. We suggest that
      products of the enzymatic activity of phospholipases directly interfere with host
      cell signal transduction pathways, thus leading to persistent NF-kappaB
      activation via persistent IkappaBbeta degradation.

PMID- 9256494
TI  - Construction of hybrid proteins that migrate retrogradely and transynaptically
      into the central nervous system.
AB  - The nontoxic proteolytic C fragment of tetanus toxin (TTC peptide) has the same
      ability to bind nerve cells and be retrogradely transported through a synapse as
      the native toxin. We have investigated its potential use as an in vivo
      neurotropic carrier. In this work we show that a hybrid protein encoded by the
      lacZ-TTC gene fusion retains the biological functions of both proteins in vivo
      i.e. , retrograde transynaptic transport of the TTC fragment and beta
      galactosidase enzymatic activity. After intramuscular injection, enzymatic
      activity could be detected in motoneurons and connected neurons of the brainstem
      areas. This strategy could be used to deliver a biological activity to neurons
      from the periphery to the central nervous system. Such a hybrid protein could
      also be used to map synaptic connections between neural cells.

PMID- 9256495
TI  - Pattern of neuronal activity associated with conscious and unconscious processing
      of visual signals.
AB  - Following striate cortex damage in monkeys and humans there can be residual
      function mediated by parallel visual pathways. In humans this can sometimes be
      associated with a "feeling" that something has happened, especially with rapid
      movement or abrupt onset. For less transient events, discriminative performance
      may still be well above chance even when the subject reports no conscious
      awareness of the stimulus. In a previous study we examined parameters that yield
      good residual visual performance in the "blind" hemifield of a subject with
      unilateral damage to the primary visual cortex. With appropriate parameters we
      demonstrated good discriminative performance, both with and without conscious
      awareness of a visual event. These observations raise the possibility of imaging
      the brain activity generated in the "aware" and the "unaware" modes, with matched
      levels of discrimination performance, and hence of revealing patterns of brain
      activation associated with visual awareness. The intact hemifield also allows a
      comparison with normal vision. Here we report the results of a functional
      magnetic resonance imaging study on the same subject carried out under aware and
      unaware stimulus conditions. The results point to a shift in the pattern of
      activity from neocortex in the aware mode, to subcortical structures in the
      unaware mode. In the aware mode prestriate and dorsolateral prefrontal cortices
      (area 46) are active. In the unaware mode the superior colliculus is active,
      together with medial and orbital prefrontal cortical sites.

PMID- 9256497
TI  - Directing gene expression to cerebellar granule cells using gamma-aminobutyric
      acid type A receptor alpha6 subunit transgenes.
AB  - Expression of the gamma-aminobutyric acid type A receptor alpha6 subunit gene is
      restricted to differentiated granule cells of the cerebellum and cochlear
      nucleus. The mechanisms underlying this limited expression are unknown. Here we
      have characterized the expression of a series of alpha6-based transgenes in adult
      mouse brain. A DNA fragment containing a 1-kb portion upstream of the start
      site(s), together with exons 1-8, can direct high-level cerebellar granule cell
      specific reporter gene expression. Thus powerful granule cell-specific
      determinants reside within the 5' half of the alpha6 subunit gene body. This
      intron-containing transgene appears to lack the cochlear nucleus regulatory
      elements. It therefore provides a cassette to deliver gene products solely to
      adult cerebellar granule cells.

PMID- 9256496
TI  - Inhibition of the electrostatic interaction between beta-amyloid peptide and
      membranes prevents beta-amyloid-induced toxicity.
AB  - The accumulation of beta-amyloid peptides (Abeta) into senile plaques is one of
      the hallmarks of Alzheimer disease. Aggregated Abeta is toxic to cells in culture
      and this has been considered to be the cause of neurodegeneration that occurs in
      the Alzheimer disease brain. The discovery of compounds that prevent Abeta
      toxicity may lead to a better understanding of the processes involved and
      ultimately to possible therapeutic drugs. Low nanomolar concentrations of Abeta1
      42 and the toxic fragment Abeta25-35 have been demonstrated to render cells more
      sensitive to subsequent insults as manifested by an increased sensitivity to
      formazan crystals following MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5
      diphenyltetrazolium bromide) reduction. Formation of the toxic beta-sheet
      conformation by Abeta peptides is increased by negatively charged membranes. Here
      we demonstrate that phloretin and exifone, dipolar compounds that decrease the
      effective negative charge of membranes, prevent association of Abeta1-40 and
      Abeta25-35 to negatively charged lipid vesicles and Abeta induced cell toxicity.
      These results suggest that Abeta toxicity is mediated through a nonspecific
      physicochemical interaction with cell membranes.

PMID- 9256498
TI  - A single dose of kainic acid elevates the levels of enkephalins and activator
      protein-1 transcription factors in the hippocampus for up to 1 year.
AB  - Neuronal plasticity plays a very important role in brain adaptations to
      environmental stimuli, disease, and aging processes. The kainic acid model of
      temporal lobe epilepsy was used to study the long-term anatomical and biochemical
      changes in the hippocampus after seizures. Using Northern blot analysis,
      immunocytochemistry, and Western blot analysis, we have found a long-term
      elevation of the proconvulsive opioid peptide, enkephalin, in the rat
      hippocampus. We have also demonstrated that an activator protein-1 transcription
      factor, the 35-kDa fos-related antigen, can be induced and elevated for at least
      1 year after kainate treatment. This study demonstrated that a single systemic
      injection of kainate produces almost permanent increases in the enkephalin and an
      activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the
      rat hippocampus, and it is likely that these two events are closely associated
      with the molecular mechanisms of induction of long-lasting enhanced seizure
      susceptibility in the kainate-induced seizure model. The long-term expression of
      the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus
      also suggests an important role in the recurrent seizures of temporal lobe
      epilepsy.

PMID- 9256499
TI  - Immediate and simultaneous sensory reorganization at cortical and subcortical
      levels of the somatosensory system.
AB  - The occurrence of cortical plasticity during adulthood has been demonstrated
      using many experimental paradigms. Whether this phenomenon is generated
      exclusively by changes in intrinsic cortical circuitry, or whether it involves
      concomitant cortical and subcortical reorganization, remains controversial. Here,
      we addressed this issue by simultaneously recording the extracellular activity of
      up to 135 neurons in the primary somatosensory cortex, ventral posterior medial
      nucleus of the thalamus, and trigeminal brainstem complex of adult rats, before
      and after a reversible sensory deactivation was produced by subcutaneous
      injections of lidocaine. Following the onset of the deactivation, immediate and
      simultaneous sensory reorganization was observed at all levels of the
      somatosensory system. No statistical difference was observed when the overall
      spatial extent of the cortical (9.1 +/- 1.2 whiskers, mean +/- SE) and the
      thalamic (6.1 +/- 1.6 whiskers) reorganization was compared. Likewise, no
      significant difference was found in the percentage of cortical (71.1 +/- 5.2%)
      and thalamic (66. 4 +/- 10.7%) neurons exhibiting unmasked sensory responses.
      Although unmasked cortical responses occurred at significantly higher latencies
      (19.6 +/- 0.3 ms, mean +/- SE) than thalamic responses (13. 1 +/- 0.6 ms),
      variations in neuronal latency induced by the sensory deafferentation occurred as
      often in the thalamus as in the cortex. These data clearly demonstrate that
      peripheral sensory deafferentation triggers a system-wide reorganization, and
      strongly suggest that the spatiotemporal attributes of cortical plasticity are
      paralleled by subcortical reorganization.

PMID- 9256501
TI  - Orderly cortical representation of vowels based on formant interaction.
AB  - Psychophysical experiments have shown that the discrimination of human vowels
      chiefly relies on the frequency relationship of the first two peaks F1 and F2 of
      the vowel's spectral envelope. It has not been possible, however, to relate the
      two-dimensional (F1, F2)-relationship to the known organization of frequency
      representation in auditory cortex. We demonstrate that certain spectral
      integration properties of neurons are topographically organized in primary
      auditory cortex in such a way that a transformed (F1,F2) relationship sufficient
      for vowel discrimination is realized.

PMID- 9256500
TI  - Carboxyfullerenes as neuroprotective agents.
AB  - Two regioisomers with C3 or D3 symmetry of water-soluble carboxylic acid C60
      derivatives, containing three malonic acid groups per molecule, were synthesized
      and found to be equipotent free radical scavengers in solution as assessed by EPR
      analysis. Both compounds also inhibited the excitotoxic death of cultured
      cortical neurons induced by exposure to N-methyl-D-aspartate (NMDA), alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or oxygen-glucose
      deprivation, but the C3 regioisomer was more effective than the D3 regioisomer,
      possibly reflecting its polar nature and attendant greater ability to enter lipid
      membranes. At 100 microM, the C3 derivative fully blocked even rapidly triggered,
      NMDA receptor-mediated toxicity, a form of toxicity with limited sensitivity to
      all other classes of free radical scavengers we have tested. The C3 derivative
      also reduced apoptotic neuronal death induced by either serum deprivation or
      exposure to Abeta1-42 protein. Furthermore, continuous infusion of the C3
      derivative in a transgenic mouse carrying the human mutant (G93A) superoxide
      dismutase gene responsible for a form of familial amyotrophic lateral sclerosis,
      delayed both death and functional deterioration. These data suggest that polar
      carboxylic acid C60 derivatives may have attractive therapeutic properties in
      several acute or chronic neurodegenerative diseases.

PMID- 9256502
TI  - Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell
      development.
AB  - The Brn-3 subfamily of POU-domain transcription factor genes consists of three
      highly homologous members-Brn-3a, Brn-3b, and Brn-3c-that are expressed in
      sensory neurons and in a small number of brainstem nuclei. This paper describes
      the role of Brn-3c in auditory and vestibular system development. In the inner
      ear, the Brn-3c protein is found only in auditory and vestibular hair cells, and
      the Brn-3a and Brn-3b proteins are found only in subsets of spiral and vestibular
      ganglion neurons. Mice carrying a targeted deletion of the Brn-3c gene are deaf
      and have impaired balance. These defects reflect a complete loss of auditory and
      vestibular hair cells during the late embryonic and early postnatal period and a
      secondary loss of spiral and vestibular ganglion neurons. Together with earlier
      work demonstrating a loss of trigeminal ganglion neurons and retinal ganglion
      cells in mice carrying targeted disruptions in the Brn-3a and Brn-3b genes,
      respectively, the Brn-3c phenotype reported here demonstrates that each of the
      Brn-3 genes plays distinctive roles in the somatosensory, visual, and
      auditory/vestibular systems.

PMID- 9256503
TI  - Glycine-induced long-term potentiation is associated with structural and
      functional modifications of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic
      acid receptors.
AB  - Global long-term potentiation (LTP) was induced in organotypic hippocampal slice
      cultures by a brief application of 10 mM glycine. Glycine-induced LTP was
      occluded by previous theta burst stimulation-induced potentiation, indicating
      that both phenomena share similar cellular processes. Glycine-induced LTP was
      associated with increased [3H]alpha-amino-3-hydroxyl-5-methyl-4
      isoxazolepropionic acid (AMPA) binding in membrane fractions as well as increased
      amount of a selective spectrin breakdown product generated by calpain-mediated
      spectrin proteolysis. Antibodies against the C-terminal (C-Ab) and N-terminal (N
      Ab) domains of GluR1 subunits were used to evaluate structural changes in AMPA
      receptor properties resulting from glycine-induced LTP. No quantitative or
      qualitative changes were observed in Western blots from membrane fractions
      prepared from glycine-treated slices with C-Ab. In contrast, Western blots
      stained with N-Ab revealed the formation of a 98-kDa species of GluR1 subunits as
      well as an increased amount of immunoreactivity after glycine-induced LTP. The
      amount of spectrin breakdown product was positively correlated with the amount of
      the 98-kDa species of GluR1 after glycine treatment. Functional modifications of
      AMPA receptors were evaluated by determining changes in the effect of pressure
      applied AMPA on synaptic responses before and after glycine-induced LTP. Glycine
      treatment produced a significant increase in AMPA receptor function after
      potentiation that correlated with the degree of potentiation. The results
      indicate that LTP induction produces calpain activation, truncation of the C-Ab
      domain of GluR1 subunits of AMPA receptors, and increased AMPA receptor function.
      They also suggest that insertion of new receptors takes place after LTP
      induction.

PMID- 9256505
TI  - In vitro repair of oxidative DNA damage by human nucleotide excision repair
      system: possible explanation for neurodegeneration in xeroderma pigmentosum
      patients.
AB  - Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by
      sunlight and, as a consequence, develop multiple cancers in areas exposed to
      light. The second most common sign, present in 20-30% of XP patients, is a set of
      neurological abnormalities caused by neuronal death in the central and peripheral
      nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so
      the cause of neurodegeneration in XP patients remains unexplained. In this study,
      we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol,
      are excised from DNA in vitro by the same enzyme system responsible for removing
      pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP
      neurological disease may be caused by defective repair of lesions that are
      produced in nerve cells by reactive oxygen species generated as by-products of an
      active oxidative metabolism.

PMID- 9256504
TI  - Endocrine modulation of the neurotoxicity of gp120: implications for AIDS-related
      dementia complex.
AB  - HIV infection often involves the development of AIDS-related dementia complex, a
      variety of neurologic, neuropsychologic, and neuropathologic impairments. A
      possible contributor to AIDS-related dementia complex is the HIV envelope
      glycoprotein gp120, which damages neurons via a complex glutamate receptor- and
      calcium-dependent cascade. We demonstrate an endocrine modulation of the
      deleterious effects of gp120 in primary hippocampal and cortical cultures.
      Specifically, we observe that gp120-induced calcium mobilization and
      neurotoxicity are exacerbated by glucocorticoids, the adrenal steroids secreted
      during stress. Importantly, this deleterious synergy can occur between gp120 and
      synthetic glucocorticoids (such as prednisone or dexamethasone) that are used
      clinically in high concentrations to treat severe cases of the Pneumocystis
      carinii pneumonia typical of HIV infection. Conversely, we also observe that
      estradiol protects neurons from the deleterious actions of gp120, reducing
      toxicity and calcium mobilization.

PMID- 9256506
TI  - Deltorphin transport across the blood-brain barrier.
AB  - In vivo antinociception studies demonstrate that deltorphins are opioid peptides
      with an unusually high blood-brain barrier penetration rate. In vitro, isolated
      bovine brain microvessels can take up deltorphins through a saturable
      nonconcentrative permeation system, which is apparently distinct from previously
      described systems involved in the transport of neutral amino acids or of
      enkephalins. Removing Na+ ions from the incubation medium decreases the carrier
      affinity for deltorphins (-25%), but does not affect the Vmax value of the
      transport. The nonselective opiate antagonist naloxone inhibits deltorphin uptake
      by brain microvessels, but neither the selective delta-opioid antagonist
      naltrindole nor a number of opioid peptides with different affinities for delta-
      or mu-opioid receptors compete with deltorphins for the transport. Binding
      studies demonstrate that mu-, delta-, and kappa-opioid receptors are undetectable
      in the microvessel preparation. Preloading of the microvessels with L-glutamine
      results in a transient stimulation of deltorphin uptake. Glutamine-accelerated
      deltorphin uptake correlates to the rate of glutamine efflux from the
      microvessels and is abolished by naloxone.

PMID- 9256508
TI  - Pattern changes of pituitary peptides in rat after salt-loading as detected by
      means of direct, semiquantitative mass spectrometric profiling.
AB  - We have established a differential peptide display method, based on a mass
      spectrometric technique, to detect peptides that show semiquantitative changes in
      the neurointermediate lobe (NIL) of individual rats subjected to salt-loading. We
      employed matrix-assisted laser desorption/ionization mass spectrometry, using a
      single-reference peptide in combination with careful scanning of the whole
      crystal rim of the matrix-analyte preparation, to detect in a semiquantitative
      manner the molecular ions present in the unfractionated NIL homogenate.
      Comparison of the mass spectra generated from NIL homogenates of salt-loaded and
      control rats revealed a selective and significant decrease in the intensities of
      several molecular ion species of the NIL homogenates from salt-loaded rats. These
      ion species, which have masses that correspond to the masses of oxytocin,
      vasopressin, neurophysins, and an unidentified putative peptide, were
      subsequently chemically characterized. We confirmed that the decreased molecular
      ion species are peptides derived exclusively from propressophysin and
      prooxyphysin (i.e., oxytocin, vasopressin, and various neurophysins). The
      putative peptide is carboxyl-terminal glycopeptide. The carbohydrate moiety of
      the latter peptide was determined by electrospray tandem MS as bisected
      biantennary Hex3HexNAc5Fuc. This posttranslational modification accounts for the
      mass difference between the predicted mass of the peptide based on cDNA studies
      and the measured mass of the mature peptide.

PMID- 9256507
TI  - A substance P (neurokinin-1) receptor mutant carboxyl-terminally truncated to
      resemble a naturally occurring receptor isoform displays enhanced responsiveness
      and resistance to desensitization.
AB  - Two isoforms of the substance P (SP) receptor, differing in the length of the
      cytoplasmic carboxyl-terminus by approximately 8 kDa, have been detected
      previously in rat salivary glands and other tissues. The binding and functional
      properties of these two isoforms have been investigated using full-length (407
      amino acids) and carboxyl-terminally truncated (324 amino acids) rat SP receptors
      transfected stably into Chinese hamster ovary cells. Both the full-length and the
      truncated receptor bound radiolabeled SP with a similar Kd ( approximately 0.1
      nM). The average number of high affinity SP binding sites per cell was 1.0 x
      10(5) and 0.3 x 10(5) for the full-length and the truncated SP receptor,
      respectively. In both cell lines, SP induced a rapid but transient increase in
      cytosolic calcium concentration ([Ca2+]i), which consisted of the release of Ca2+
      from intracellular stores and the influx of extracellular Ca2+. Both components
      are dependent on phospholipase C activation. Although the full-length and the
      truncated receptor utilize the same calcium pathways, they differ in their EC50
      values (0.28 nM for the full-length; 0.07 nM for the truncated). These
      differences in responsiveness may be related to the observed differences in
      receptor desensitization. The truncated receptor, in contrast to the full-length
      receptor, does not undergo rapid and long-lasting desensitization. Cells
      possessing the short isoform of the SP receptor would thus be expected to exhibit
      a prolonged responsiveness.

PMID- 9256509
TI  - Characterization of the alpha1B-adrenergic receptor gene promoter region and
      hypoxia regulatory elements in vascular smooth muscle.
AB  - We previously demonstrated that alpha1B-adrenergic receptor (AR) gene
      transcription, mRNA, and functionally coupled receptors increase during 3% O2
      exposure in aorta, but not in vena cava smooth muscle cells (SMC). We report here
      that alpha1BAR mRNA also increases during hypoxia in liver and lung, but not
      heart and kidney. A single 2.7-kb alpha1BAR mRNA was detected in aorta and vena
      cava during normoxia and hypoxia. The alpha1BAR 5' flanking region was sequenced
      to -2,460 (relative to ATG +1). Transient transfection experiments identify the
      minimal promoter region between -270 and -143 and sequence between -270 and -248
      that are required for transcription of the alpha1BAR gene in aorta and vena cava
      SMC during normoxia and hypoxia. An ATTAAA motif within this sequence
      specifically binds aorta, vena cava, and DDT1MF-2 nuclear proteins, and
      transcription primarily initiates downstream of this motif at approximately -160
      in aorta SMC. Sequence between -837 and -273 conferred strong hypoxic induction
      of transcription in aorta, but not in vena cava SMC, whereas the cis-element for
      the transcription factor, hypoxia-inducible factor 1, conferred hypoxia-induced
      transcription in both aorta and vena cava SMC. These data identify sequence
      required for transcription of the alpha1BAR gene in vascular SMC and suggest the
      atypical TATA-box, ATTAAA, may mediate this transcription. Hypoxia-sensitive
      regions of the alpha1BAR gene also were identified that may confer the
      differential hypoxic increase in alpha1BAR gene transcription in aorta, but not
      in vena cava SMC.

PMID- 9256510
TI  - Myofibrillogenesis visualized in living embryonic cardiomyocytes.
AB  - Myofibril formation was visualized in cultured live cardiomyocytes that were
      transfected with plasmids expressing green fluorescent protein (GFP) linked to
      the Z-band protein, alpha-actinin. The expression of this fluorescent protein
      provided an in vivo label for structures containing alpha-actinin. The GFP-alpha
      actinin fusion protein was incorporated into Z-bands, intercalated discs, and
      attachment plaques, as well as into the punctate aggregates, or Z-bodies, that
      are thought to be the precursors of Z-bands. Observations of live cells over
      several days in culture permitted us to test aspects of several theories of
      myofibril assembly that had been proposed previously based on the study of fixed
      cells. Fine fibrils, called premyofibrils, that formed de novo at the spreading
      edges of cardiomyocytes, contained punctate concentrations of alpha-actinin,
      termed Z-bodies. The punctate Z-bodies grew and aligned with Z-bodies in adjacent
      fibrils. With increasing time, adjacent fibrils and Z-bodies appeared to fuse and
      form mature myofibrils and Z-bands in cytoplasmic regions where the linear arrays
      of Z-bodies had been. These new myofibrils became aligned with existing
      myofibrils at their Z-bands to form myofibrils that spanned the length of the
      spread cell. These results are consistent with a model that postulates that the
      fibrils that form de novo near the cell membrane are premyofibrils-i.e., the
      precursors of mature myofibrils.

PMID- 9256511
TI  - A hypothalamic follicle-stimulating hormone-releasing decapeptide in the rat.
AB  - Previous studies indicated that there is a separate hypothalamic control of
      follicle-stimulating hormone (FSH) release distinct from that of luteinizing
      hormone (LH). An FSH-releasing factor (FSHRF) was purified from rat and sheep
      hypothalami, but has not been isolated. We hypothesized that FSHRF might be an
      analogue of mammalian luteinizing hormone-releasing hormone (m-LHRH) and
      evaluated the activity of many analogues of m-LHRH and of the known LHRHs found
      in lower forms. Here we demonstrate that lamprey (l) LHRH-III has a potent, dose
      related FSH- but not LH-releasing action on incubated hemipituitaries of male
      rats. l-LHRH-I on the other hand, had little activity to release either FSH or
      LH. m-LHRH was equipotent to l-LHRH-III to release FSH, but also had a high
      potency to release LH in contrast to l-LHRH-III that selectively released FSH.
      Chicken LHRH-II had considerable potency to release both LH and FSH, but no
      selectivity in its action. Salmon LHRH had much less potency than the others
      tested, except for l-LHRH-I, and no selectivity in its action. Because
      ovariectomized, estrogen, progesterone-treated rats are a sensitive in vivo assay
      for FSH- and LH-releasing activity, we evaluated l-LHRH-III in this assay and
      found that it had a completely selective stimulatory effect on FSH release at the
      two doses tested (10 and 100 pmols). Therefore, l-LHRH-III is a highly potent and
      specific FSH-releasing peptide that may enhance fertility in animals and humans.
      It may be the long sought after m-FSHRF.

PMID- 9256512
TI  - Isolation and characterization of an amino acid-selective channel protein present
      in the chloroplastic outer envelope membrane.
AB  - The reconstituted pea chloroplastic outer envelope protein of 16 kDa (OEP16)
      forms a slightly cation-selective, high-conductance channel with a conductance of
      Lambda = 1,2 nS (in 1 M KCl). The open probability of OEP16 channel is highest at
      0 mV (Popen = 0.8), decreasing exponentially with higher potentials. Transport
      studies using reconstituted recombinant OEP16 protein show that the OEP16 channel
      is selective for amino acids but excludes triosephosphates or uncharged sugars.
      Crosslinking indicates that OEP16 forms a homodimer in the membrane. According to
      its primary sequence and predicted secondary structure, OEP16 shows neither
      sequence nor structural homologies to classical porins. The results indicate that
      the intermembrane space between the two envelope membranes might not be as freely
      accessible as previously thought.

PMID- 9256513
TI  - Looming vulnerability to threat: a cognitive paradigm for anxiety.
AB  - The concept that perceived threat or danger is a cognitive antecedent of anxiety
      is central in clinical psychology, personality psychology, and social psychology.
      The aim in the current article is to review this concept and present a new
      conception called the looming vulnerability model. Looming vulnerability is
      conceptualized as an important cognitive component of threat or danger that
      elicits anxiety, sensitizes the individual to signs of movement and threat,
      biases cognitive processing, and makes the anxiety more persistent and less
      likely to habituate. In addition, it is postulated as a principal theme that
      discriminates anxiety and focal fears from depression. The looming vulnerability
      model integrates a disparate collection of findings and integrates the
      conceptualization of anxiety and fear with ethological and developmental
      observations. The social-cognitive and evolutionary basis of the sense of looming
      vulnerability are discussed, as well as its roots in cognitive schemata (fear
      scripts), its state elicitation by several potential classes of antecedent
      conditions, and possible treatment implications.

PMID- 9256514
TI  - Pessimistic attributional style: is it specific to depression versus anxiety
      versus negative affect?
AB  - Two studies with college students explored the relationship of a pessimistic
      attributional style to positive and negative affect, as well as to depressed and
      anxious mood. Both studies revealed that a pessimistic attributional style was
      correlated with negative affect and depressed mood, but was unrelated to low
      levels of positive affect. The second study also showed a correlation with
      anxiety and that the association of pessimistic attributional style with
      emotional distress occurs for both depression-relevant (i.e. loss/failure) as
      well as anxiety-relevant (i.e. threatening) events. The second study also
      provided a longitudinal test of the diathesis-stress component of the
      reformulated helplessness theory. Results supported the hypothesis that
      pessimistic attributional style is a nonspecific diathesis for symptoms of both
      anxiety and depression. Implications for these findings for cognitive theories of
      depression are addressed.

PMID- 9256515
TI  - One-session group therapy of spider phobia: direct versus indirect treatments.
AB  - Forty-six patients with spider phobia, fulfilling the DSM-IV criteria for
      specific phobia, were assessed with behavioral, physiological and self-report
      measures. They were randomly assigned to three group treatment conditions: (1)
      direct treatment; (2) direct observation; and (3) indirect observation. All
      treatments were carried out in large groups of eight patients, and consisted of
      one 3 hr session of massed exposure and modelling. The results showed that on the
      behavioral test, measures and the specific self-report measures of spider phobia
      the direct treatment was significantly better than direct observation and
      indirect observation, which did not differ. On the physiological measures and the
      psychopathology self-report measures there were significant pre-post
      improvements, but no differences between the groups. The effects were maintained
      or furthered at the one year follow-up assessment. The proportion of clinically
      significantly improved patients were, at post-treatment, 75% in the direct
      treatment, 7% in the direct observation, and 31% in the indirect observation
      group. At follow-up, the corresponding figures were 75, 14, and 44%,
      respectively. The conclusion that can be drawn is that direct treatment is the
      treatment of choice.

PMID- 9256517
TI  - A cognitive-behavioral model of anxiety in social phobia.
AB  - The current paper presents a model of the experience of anxiety in
      social/evaluative situations in people with social phobia. The model describes
      the manner in which people with social phobia perceive and process information
      related to potential evaluation and the way in which these processes differ
      between people high and low in social anxiety. It is argued that distortions and
      biases in the processing of social/evaluative information lead to heightened
      anxiety in social situations and, in turn, help to maintain social phobia.
      Potential etiological factors as well as treatment implications are also
      discussed.

PMID- 9256516
TI  - Fatigue and sleep disorders.
AB  - Fatigue has often been confused with sleepiness and has received little study as
      an independent symptom of sleep disturbance. To investigate if fatigue is a
      common and severe symptom in sleep disordered individuals, the Fatigue Severity
      Scale (FSS) was administered to 206 patients over a 12-month period at a sleep
      disorder center. Our sample averaged 4.8 on the 7-point FSS, which is in the
      severe fatigue range. High fatigue was present in a broad range of sleep
      disorders, but was particularly high among individuals diagnosed with
      psychophysiological insomnia. A number of variables predicted fatigue (being
      female, being a smoker, high BMI, low sleep efficiency percent, and high MMPI
      average clinical scale score), but surprisingly daytime sleepiness (as measured
      by the multiple sleep latency test) did not. Apparently, daytime sleepiness and
      perceived fatigue are independent phenomena. We discussed the importance of
      attributing credence to the complaint of fatigue and suggested some areas for
      future study including further study of fatigue in insomnia, expanded
      consideration of sleep variables causing fatigue, and testing objective measures
      of fatigue.

PMID- 9256518
TI  - Using mental imagery with subclinical OCD to 'freeze' contamination in its place:
      evidence for looming vulnerability theory.
AB  - The present research examines the possibility that 'freezing' or slowing-down the
      rate at which threats can advance and thereby blocking a sense of looming
      vulnerability can reduce fears of contamination and avoidance behavior among
      individuals with obsessional symptoms. Mental imagery was used to reduce the rate
      at which threat can advance by means of instructions to imagine that
      contamination was 'frozen' in place and unable to move. Measures included self
      reports of anxiety and worry, and indirect assessments of fear and avoidance
      behavior. A parallel mental imagery condition was used to examine the possibility
      that accentuating the spread or contamination, or its 'looming', would in turn
      accentuate fear and avoidance. The results, particularly of the more unobtrusive
      measures, indicated that freeze imagery reduced fear and avoidance for the
      relatively obsessional participants. In addition, support was found that it
      reduced fear for participants with relatively higher levels of imagination.
      However, the freeze imagery paradoxically seemed to sensitize the non-obsessional
      participants to possibilities of contamination they had not previously
      considered, and thus increased their fear. The results provide support for the
      looming vulnerability model of anxiety and suggest applications to treatment.

PMID- 9256519
TI  - Thought suppression in spider phobia.
AB  - The current study examined the role of thought suppression in spider phobia.
      Spider phobic (n = 41) and non-phobic (n = 40) subjects were asked to monitor
      their thoughts for three 5 min periods. During the first period, all subjects
      were instructed to "think about anything". During the second period, half of the
      subjects received suppression instructions (i.e., subjects were explicitly asked
      "not to think of spiders"), whereas the other half once again received
      instructions to "think about anything". During the third period, all subjects
      were instructed to "think about anything". Spider-related thoughts were monitored
      on-line. Also, subjects retrospectively estimated the amount of time they had
      spent thinking about spiders. Overall, spider phobics reported higher levels of
      spider-related thoughts than non-phobic subjects. Furthermore, phobic subjects
      tried harder to suppress spider-related thoughts than non-phobic subjects.
      Finally, although some evidence was found for the counterproductive effects of
      thought suppression, its contribution to the frequency of spider-related thoughts
      was minimal.

PMID- 9256520
TI  - Strategies of thought control in obsessive-compulsive disorder.
AB  - Intrusive anxiety-provoking thoughts are a core feature of obsessive-compulsive
      disorder (OCD). Recent research suggests that individuals use five different
      techniques of thought control including: distraction, punishment, re-appraisal,
      social control, and worry. The purpose of the present study was to examine the
      strategies of thought control used by OCD patients compared to those used by non
      anxious controls. In addition, the relationship of method of thought control and
      domains of OCD-related psychopathology were investigated. Results revealed that
      OCD patients used punishment, worry, reappraisal, and social control more often
      than non-patients. Conversely, distraction was used more often by non-patients
      than OCDs. Interestingly, punishment was the strongest discriminator of OCDs and
      non-patients mostly because of the low frequency of its use by non-patients.
      Furthermore, punishment and worry were the only methods of thought control that
      correlated with OCD symptomatology. These results suggest that OCD patients may
      use maladaptive methods of thought control when faced with obsessions.

PMID- 9256521
TI  - Voluntary breath holding: not a suitable probe of the suffocation alarm in panic
      disorder.
AB  - Voluntary breath-holding duration was investigated in patients with panic
      disorder, patients with a mood disorder, and normal controls. There were no
      differences in mean breath-holding durations, but the pattern of scores was
      different among groups. Furthermore, the scores were influenced by motivational
      and cognitive factors. It is argued that voluntary breath-holding is not a
      suitable test to measure carbon dioxide sensitivity or suffocation alarm
      threshold in panic disorder.

PMID- 9256522
TI  - Screening for major depression disorders in medical inpatients with the Beck
      Depression Inventory for Primary Care.
AB  - To ascertain how effective the Beck Depression Inventory for Primary Care (BDI
      PC) was for differentiating medical inpatients who were and were not diagnosed
      with DSM-IV major depression disorders (MDD), this 7-item self-report instrument
      composed of cognitive and affective symptoms was administered to 50 medical
      inpatients along with the Depression subscale (HDS) from the Hospital Anxiety and
      Depression Scale (Zigmond & Snaith, 1983, Acta Psychiatrica Scandinavica, 67, 361
      370). The Mood Module from the Primary Care Evaluation of Mental Disorders
      (Spitzer et al., 1995, Prime-MD instruction manual updated for DSM-IV) was used
      to diagnose MDD. The internal consistency of the BDI-PC was high (alpha = 0.86),
      and it was moderately correlated with the HDS (r = 0.62, P < 0.001). The BDI-PC
      was not significantly correlated with sex, age, ethnicity, or type of medical
      diagnosis. A BDI-PC cut-off score of 4 and above yielded the maximum clinical
      efficiency with both 82% sensitivity and specificity rates. The clinical utility
      of the BDI-PC for identifying medical inpatients who should be evaluated for MDD
      is discussed.

PMID- 9256523
TI  - Legacies of insight and perspective from the recent past: introduction.

PMID- 9256524
TI  - A legacy: Anna Freud's views on childhood and development.
AB  - Anna Freud's genius encompassed the study and understanding of children and
      adults, spanning the gap between theory and practice. She pioneered the method
      and theory of child psychoanalysis, and demonstrated that the applications of
      psychoanalytic theory could make a crucial difference to children at high risk of
      having their physical, emotional and intellectual well-being blighted by poverty,
      war, biological handicaps, and family breakdown.

PMID- 9256525
TI  - Erik Erikson: critical times, critical theory.
AB  - The work and legacy of Erik Erikson are described in this brief outline of his
      career, his theories, and his impact on psychoanalysis, psychology, history, and
      the broader culture. His conception of the adolescent task-weaving internal
      tastes, talents, and values together with elements of one's life history and the
      demands of one's culture into a coherent identity-has had profound effects on
      developmental psychology and the way in which sophisticated youth construct and
      describe their lives. His extension of development through adulthood and old age
      established the field of life course development. His emphasis on the impact of
      history and culture on development was a critical element in the developing field
      of ego psychology. Many of his major contributions can be fruitfully understood
      in the context of his personal history and individual qualities.

PMID- 9256526
TI  - Viewing education through a psychological lens: the contributions of Barbara
      Biber.
AB  - Barbara Bibers major contribution to child development lay in the incisiveness
      with which she viewed the child's educational experience through a psychological
      lens. The unique perspective that she brought to bear to education greatly
      expanded our vision of all that is at stake in schooling. The extraordinary depth
      of her knowledge and understanding of child development gave rise to one of the
      earliest demonstrations of the fertility of adopting an interdisciplinary,
      orthopsychiatric approach to the educational process.

PMID- 9256527
TI  - Bowlby's legacy to developmental psychology.
AB  - In formulating attachment theory, Bowlby made a number of important conceptual
      contributions to our understanding of human development. Discussed here are the
      balance (rather than the conflict) between attachment and exploration, the
      concept of internal working models; and the parent as a psychological secure
      base. In addition, Bowlby's "theory of reality" is examined, integration of
      Bowlby's and Erikson's ideas regarding attachment and culture is suggested, and
      Bowlby's open-minded approach to theory construction is acknowledged.

PMID- 9256528
TI  - Defense reactions and coping strategies in normal adolescents.
AB  - In exploring the relationship between defense reactions and coping strategies in
      a non-clinic sample of adolescents (N = 81), we assessed: defense structure by
      the Bond Defense Style Questionnaire (DSQ); coping behaviors by the Coping
      Responses Inventory-Youth Form (CRI-Youth); and general adjustment by Global
      Assessment of Functioning (GAF) ratings. Defense reactions and coping strategies
      were modestly associated and made independent contributions in predicting the
      GAF. Mature and immature defenses and avoidance coping comprised the optimal
      combination in predicting the GAF, accounting for 20% of GAF variance. It is
      therefore important to assess both unconscious and conscious processes when
      assessing general functioning in normal adolescents.

PMID- 9256529
TI  - Tuberculosis remains "the captain of all these men of death".

PMID- 9256530
TI  - PHLS mycobacteriology reference services in England and Wales.
AB  - Tuberculosis (TB) is the most important cause of infectious disease in the world,
      with eight million new cases and three million deaths each year. The increasing
      incidence of TB in the developed and the developing world, increasing drug
      resistance, and the occurrence of nosocomial outbreaks of drug sensitive as well
      as drug resistant TB has led the PHLS to establish TB as a priority area. This
      article reviews the enhanced reference services for mycobacteriology provided by
      the PHLS in England and Wales. These include microscopy and culture on solid and
      liquid media, rapid culture systems, identification of mycobacteria using
      macroscopic, microscopic, growth, and biochemical characteristics, and molecular
      DNA analysis. The Mycobacterium Reference Unit (MRU) provides rapid molecular DNA
      amplification techniques to identify Mycobacterium tuberculosis in specimens. All
      four PHLS Regional Centres test isolates for drug susceptibility. This work is
      quality controlled by MRU, which is one of the World Health Organisation's
      reference centres for global surveillance on drug resistance in tuberculosis.
      National data on drug resistance are collated through 'Mycobnet', a surveillance
      scheme run through the collaboration of PHLS and other UK reference centres and
      the PHLS Communicable Disease Surveillance Centre.

PMID- 9256531
TI  - PHLS work on the surveillance and epidemiology of tuberculosis.
AB  - The re-emergence worldwide of tuberculosis as a major threat to public health and
      continuing and changing challenges in the control of tuberculosis in England and
      Wales provide the basis for the designation, by the PHLS, of tuberculosis as a
      priority area. In addition to the mycobacteriology reference services provided by
      the PHLS in England and Wales (summarised in an accompanying article) the PHLS
      contributes to the control of tuberculosis through its surveillance and other
      epidemiological work. This article summarises the range of this work, emphasising
      the collaborative nature of the effort required for surveillance, prevention, and
      control of tuberculosis.

PMID- 9256532
TI  - Investigation of tuberculosis in an adolescent. The Outbreak Control Team.
AB  - In February 1996, sputum smear positive tuberculosis was diagnosed in an
      adolescent white girl born in the United Kingdom. The investigation was complex
      because the index case had attended two schools and had a large extended family.
      The extent of transmission was consistent with "adult" pulmonary disease; eight
      previously unvaccinated contacts showed evidence of infection: one had proven
      tuberculosis, four had pulmonary radiological changes and positive Heaf test
      results, and three had positive Heaf test results. Seven of the eight were
      family/ household contacts, the eighth was a school contact. Current guidelines
      for the management of tuberculosis in schools were followed in this investigation
      and it was concluded that they remain appropriate. The source of infection for
      the index case was not definitely established. It may have been an adult who
      presented with active tuberculosis in 1994. The index case had erythema nodosum
      with a normal chest radiograph in 1993.

PMID- 9256533
TI  - Orofacial clefts in Hungary. Epidemiological and genetic data, primary
      prevention.
AB  - The occurrences (birth prevalences) of different types of isolated and multiple
      orofacial clefts are known in Hungary. The empiric risk figures in the first
      degree relatives of probands with cleft lip +/- cleft palate, cleft palate, Robin
      sequence and multiple congenital abnormalities including orofacial clefts as
      component defects were also determined. Finally the recent controversial data
      concerning the primary prevention of isolated orofacial clefts by
      periconceptional folic acid-containing multivitamins are summarized.

PMID- 9256534
TI  - Recent progress in treating patients with cleft palate.
AB  - Over the last 4 decades remarkable progress has been made in the treatment of
      cleft palate: the rate of attaining normal or nearly normal speech after surgery
      has risen from about 65% 40 years ago to nearly 90% or more nowadays. One of the
      main factors is intratracheal intubation anesthesia that has made the surgery
      much safer and easier. Improved surgical technique and speech therapy also played
      a great role. This paper deals with two problems: (1) Slight velopharyngeal
      incompetence: The combined use of fiberscopy and fluorovideoscopy can provide
      useful information as to: (a) the exact place of the faulty articulation, (b) the
      detailed pattern of inconsistent velopharyngeal function, (c) changes in
      articulation induced by speech therapy, and (d) the relation between
      velopharyngeal function and faulty articulation. All the above information
      greatly facilitates speech therapy for cleft palate speech. It should be done
      with utmost care though due to possible adverse effects of radiation. (2)
      Analysis of faulty articulation. It was revealed that faulty articulations such
      as laryngeal fricative and affricates, pharyngeal stop, and glottal stop in cleft
      palate speech, secondary to velopharyngeal incompetence, were produced by
      articulation in the larynx at various sites such as the epiglottis, arytenoids,
      aryepiglottic folds and vocal folds. These faulty articulation points were
      located lower than supposed on the basis of auditory perception.

PMID- 9256535
TI  - Aspects of assessment and management of velopharyngeal dysfunction in developing
      countries.
AB  - Proper assessment of patients with velopharyngeal valve incompetence is a
      mandatory prerequisite for optimal management. The protocol of assessment of Ain
      Shams University, Phoniatric Department, uses three levels of assessment of
      velopharyngeal valve incompetence according to the complexity of the
      armamentarium used. This allows application of those parts of the protocol that
      suit the needs of the different socioeconomic levels and geographical locations.
      Firstly, the elementary diagnostic procedures, which are rather simple,
      noninvasive, but essentially subjective. Despite the clinical feasibility of
      these procedures, documentation of the data is made utilizing the tools at the
      second level of assessment in that protocol (clinical diagnostic aids). This
      level comprises video-nasofiberscopy and high fidelity voice recording. An
      attempt to extract quasi-quantitative measures from the hitherto qualitative
      video-nasofiberscopy is made. The third level of assessment, namely additional
      instrumental measures, comprises CT scanning of the velopharyngeal port,
      aerodynamics, and acoustic analysis. The results of the three levels of the
      protocol are presented. Their significance and clinical efficacy are discussed.
      Some community-related problems that have faced the cleft palate team are
      outlined. Their sociocultural significance in a developing country is discussed.

PMID- 9256536
TI  - Diagnostic value of articulation tests with individuals having clefts.
AB  - Articulation testing provides a structure for evaluating children with cleft or
      velopharyngeal incompetency in a specific manner so that they can be compared
      with normative data and later to themselves. Results from an articulation test
      should always be compared to the precept of what is heard in conversation,
      specifically on articulation, nasality, and velopharyngeal competency. Analysis
      of an articulation test provides data for the speech clinician to develop a
      therapy program which is realistic and structured. Articulation tests also help
      clinicians evaluate the child's progress.

PMID- 9256537
TI  - A proposal for standardization of speech and hearing evaluations to assess
      velopharyngeal function.
AB  - The article comprises the proposal made by the Cleft Palate Committee of IALP to
      standardize the parameters of the speech and hearing evaluation in individuals
      with cleft palate/velopharyngeal incompetence (CP/VPI). The suggested parameters
      are the following: nasal resonance, nasal escape, articulation and its disorders,
      facial grimacing, speech intelligibility, patient teachability, expressive
      language and voice. The authors recommend a five-point scale description system,
      which can be used also for assessment of hearing, velopharyngeal competence and
      other attributes of the CP/VPI individual. The most important diagnostic
      procedures are: X-ray (video/cinefluoroscopy), nasopharyngoscopy, nasometry; in
      dubious cases it is also fundamental to clarify the etiology with
      electrophysiological methods. The utilization of this proposal might contribute
      to a more accurate diagnosis and a more effective treatment on an international
      basis.

PMID- 9256538
TI  - Functional results with the team care of cleft lip and palate patients in Bergen,
      Norway. The Bergen Cleft Palate-Craniofacial Team, Norway.
AB  - There is international consensus about some fundamental elements concerning
      treatment of cleft lip and palate (CLP): (1) multidisciplinary teamwork, (2)
      centralization, (3) team continuity, (4) long-term treatment planning (from birth
      to adulthood), (5) documentation, (6) evaluation, (7) follow-up studies, (8)
      research and (9) quality assurance. Every year 120-140 children are born with CLP
      in Norway (2 per 1,000 live births). For more than four decades the treatment of
      CLP has been centralized to the University Clinics in Oslo and Bergen. The cost
      of treatment as well as the travel expenditures for patients born with facial
      clefts are paid by the Norwegian government (social security). In a speech study
      of 180 6-year-old children with CLP/CP first operated in Bergen during 1973-1981,
      normal resonance was found in 76.7% of the children, moderate hypernasality in
      11.7%, while 11.6% had marked hypernasality.

PMID- 9256539
TI  - Prevention of severe mucosecretory ear disease and its complications in patients
      with cleft lip and palate malformations.
AB  - Morphological and functional alterations in patients with cleft lip and palate
      act as predisposing factors in eustachian tube dysfunctions and as a result
      thereof in the occurrence of mucosecretory ear disease (MSED) and its
      complications. Development of MSED is the result of tube dysfunction and it
      consists of: (a) fluctuating conductive hearing loss, (b) swallowing alterations
      and (c) respiratory functional disorders. Once this syndrome is confirmed in
      children with clefts, action must be taken through a coordinated
      multidisciplinary approach with plastic surgery, odontology, and speech therapy
      to achieve morphological and functional reconstruction, thus allowing early
      middle ear ventilation.

PMID- 9256540
TI  - Indications for combined orthodontic and surgical (orthognathic) treatments of
      dentofacial deformities in cleft lip and palate patients and their impact on
      velopharyngeal function.
AB  - Malformations, deformations and abnormal intermaxillary relationships varying in
      severity can be found in cleft lip and/or palate children. Such multiple
      deformities have an influence on speech resonance and articulation, as well as on
      masticatory, auditive and respiratory functions. Therefore, a multidisciplinary
      team should monitor these patients from birth on to adulthood. This article
      describes our treatment protocol, discusses the limitations of dental orthopedic
      action and the indications for orthognathic surgery. Timing and techniques of
      different surgical interventions are presented and the impact of these procedures
      on velopharyngeal function is evaluated.

PMID- 9256541
TI  - Flap surgery: experience with 1,030 operations and cephalometric investigation.
AB  - The authors report 1,030 (velo)pharyngoplasties performed in 40 years. The
      anatomical result was good in 98%, hyperrhinophony ceased or became minimal in
      90% after surgery. The surgical indication and technique, the operative
      complications and the factors influencing the functional effect are discussed. In
      the present investigation cephalograms of 53 unilateral cleft lip and palate
      (UCLP) patients with inferiorly based pharyngeal flap were compared with the
      cephalograms of 38 UCLP patients without pharyngeal flap operation. Pharyngeal
      flap surgery has an adverse effect on the growing face both in the sagittal and
      vertical dimensions, but the changes do not reach a degree that would justify the
      abandonment of the good functional effect of velopharyngoplasty.

PMID- 9256542
TI  - Critical reading using the READER acronym by experienced general practitioners
      (G.P.s) and by G.P. registrars in southern and Northern Ireland.
AB  - The READER acronym describes a simple easily applied method of critical reading,
      an important skill for general practitioners (GPs). The aim of the study was to
      evaluate an abstract using the READER method, and to compare the appraisal by GP
      registrars in Southern Ireland with those of GP registrars in Northern Ireland
      and those previously recorded by experienced GPs at the Conference of Teachers of
      the Irish College of General Practitioners. General practice registrars (n = 41)
      in Southern Ireland participated in a critical reading workshop at which they
      appraised the abstract of a sample paper using the READER model for critical
      appraisal. A group of GP registrars (n = 10) in Northern Ireland, and experienced
      GPs (n = 35) at the Conference of Teachers of the Irish College of General
      Practitioners evaluated the complete paper using a similar methodology. There was
      no statistically significant difference between scores recorded by GP registrars
      in Southern Ireland and their Northern Irish counterparts, nor was there a
      statistically significant difference with experienced GP teachers. The READER
      model for critical reading provides GP registrars with a useful tool for critical
      evaluation of medical literature. GP registrars in Southern Ireland, Northern
      Ireland, and experienced GP's from the Conference of Teachers in Ireland recorded
      similar results and the study appraised, while dealing with an intervention in
      one practice in south west England, appeared relevant and applicable to
      participants from other locations in a different health care system.

PMID- 9256543
TI  - Impact of litigation on quality of life outcomes in patients with chronic low
      back pain.
AB  - Low back pain progresses to chronic low back pain (CLBP) in 5-10 per cent of
      patients. A Multi-disciplinary Pain Management Programme was tested in 20
      patients (m = 4, f = 16). This regime involved psychological and behaviour
      modification strategies, combined with intensive exercise. Treatment outcome in
      terms of impairment was assessed by lumbar flexibility, trunk muscle endurance
      and pain. The disability assessed was exercise fitness and handicap was assessed
      using the Sickness Impact Profile (SIP) to define the impact of the condition on
      the patient's life. Overall the patients showed significant improvement (p <
      0.05) in all of the measured variables. Patients with on-going litigation however
      (n = 11) showed no significant improvement in the SIP quality of life score,
      although they shared the significant improvements attained by the whole group in
      the domains of impairment (lumbar flexibility, trunk muscle endurance and pain)
      and disability (exercise fitness).

PMID- 9256544
TI  - Suppurative complications of infective sinusitis.
AB  - We report three cases of suppurative sinusitis that presented to our casualty
      department over a one week period. All three patients suffered complications of
      the disease secondary to extension of the inflammatory process beyond the bony
      confines of the sinus. None of the patients had previous history of sinus
      disease. We wish to remind the clinician that such complications still exist and
      we highlight the necessity of rapid diagnosis and early intervention in the
      management of complicated sinus disease.

PMID- 9256545
TI  - Long-term semi-quantitative follow-up of Helicobacter pylori associated
      gastritis.
AB  - Helicobacter pylori infection has been implicated with the development of gastric
      carcinoma and lymphoma. We studied the long-term effects of H. pylori infection
      on gastric mucosa. Ten patients with Helicobacter pylori infection underwent
      repeat endoscopy and antral biopsies 8 years later. Gastric mucosal features
      (polymorphs, monocytes, intestinal metaplasia, atrophy and lymphoid aggregates)
      were graded from mild to severe (0 to 3) based on the Sydney system of gastritis
      classification. At repeat biopsy, 1 patient was negative for H. pylori after
      eradication therapy. Two patients (20 per cent) had spontaneous disappearance of
      H. pylori. One of these had intestinal metaplasia which progressed to low grade
      dysplasia. Polymorphs decreased with eradication of H. pylori (P < 0.05).
      Lymphoid aggregates increased with continued H. pylori infection but decreased
      with eradication of H. pylori (P < 0.05). Monocytes, intestinal metaplasia and
      atrophy remained unchanged. Persistent H. pylori infection appears to increase
      lymphoid aggregates and may promote its evolution into gastric lymphoma while
      eradication of H. pylori may result in a reduction of polymorphs and lymphoid
      aggregates.

PMID- 9256546
TI  - Grey matter heterotopia: an unusual association of intractable epilepsy.
AB  - Heterotopic grey matter is an abnormality of neuronal migration that has been
      reported in association with refractory epilepsy. In this study we reviewed the
      magnetic resonance (MR) imaging records of all patients undergoing MR scanning
      for evaluation of intractable epilepsy and identified sixteen patients who had
      grey matter heterotopia. The distribution of the grey matter heterotopia was
      periventricular in 9 patients, laminar in 3 and was in a "band" form in 4
      patients. Congenital anomalies associated with grey matter heterotopia in this
      study included polymicrogyria in one patient and absence of the corpus callosum
      in 2 patients. Grey matter heterotopia is an important MR finding in patients
      with intractable epilepsy.

PMID- 9256547
TI  - One hundred and fifty years of anaesthesia in obstetrics--Irish connections.

PMID- 9256548
TI  - Disseminated herpes zoster in the elderly.
AB  - We describe three cases of disseminated herpes zoster occurring in the elderly,
      and discuss the investigation and diagnosis of this condition. The presentation
      may be atypical with excoriated papular lesions. We suggest that disseminated
      herpes zoster does occur in the non-immunocompromised elderly patient, and is
      sometimes overlooked.

PMID- 9256549
TI  - Osteoporosis prevention: from vitamin D to HRT.

PMID- 9256550
TI  - Congenital nasal dermoids in children.
AB  - The case of a 27 month old male with a congenital midline nasal dermoid cyst is
      presented. The child attended the Ear, Nose and Throat outpatient's department in
      July 1995, with an external midline nasal swelling, which had been present at
      birth and was noted to be gradually increasing in size. Magnetic resonance
      imaging (MRI) showed a central defect of the nasal bones, with a soft tissue mass
      at the upper part of the nasal bridge expanding the nasal septum. There was no
      radiological evidence of intracranial extension. The child had the nasal mass
      removed under general anesthesia, through an external rhinoplasty incision.
      Histopathology confirmed that the mass was a fully excised nasal dermoid cyst.
      Current investigation and management of this condition is discussed.

PMID- 9256551
TI  - Men, medicine and machines.

PMID- 9256552
TI  - The Glucksberg & Quill amicus curiae briefs: verbatim arguments opposing assisted
      suicide.

PMID- 9256555
TI  - Object relations as a predictor of treatment outcome with chronic posttraumatic
      stress disorder.
AB  - The role of object relations as a predictor of outcome was evaluated in inpatient
      posttraumatic stress disorder (PTSD) treatment. Cohort outcome at discharge on
      psychometric indices was mixed, with limited evidence of reliable or clinically
      significant change. Treatment was associated with an overall reduction in
      utilization of inpatient psychiatric and residential domiciliary services.
      However, moderate (vs. low) levels of object relations were predictive of
      reliable change outcome, independent of demographics, Axis II diagnosis,
      symptomatic severity, or early childhood or war zone trauma exposure. The
      findings suggest that consideration should be given both to the manner in which
      patients seeking treatment for PTSD are screened and matched with a range of
      treatment or rehabilitation services and to how treatment outcome is
      conceptualized beyond symptom reduction. Rehabilitation of chronic posttraumatic
      symptomatology and associated psychosocial impairment may be facilitated by
      assessment, treatment design, and client-treatment matching on the basis of
      multidimensional psychological indices.

PMID- 9256554
TI  - Fatalism, current life satisfaction, and risk for HIV infection among gay and
      bisexual men.
AB  - This study surveyed 430 men at an urban gay pride celebration to assess fatalism,
      current life satisfaction, and perceived expected years of life among men who
      have sex with men. Analyses showed that men who engaged in unprotected anal
      intercourse outside of exclusive relationships reported a greater fatalistic
      outlook, were more dissatisfied with life, and perceived a shorter life for
      themselves than men who practiced only safer sex and men who were in exclusive
      relationships. Gay men in exclusive relationships scored higher than
      nonexclusively partnered gay men on the measure of current life satisfaction.
      These results suggest that efforts to prevent HIV infection among gay men should
      include building personal self-worth, support of long-term relationships, and
      future goal orientations.

PMID- 9256553
TI  - Enhancing motivation to reduce the risk of HIV infection for economically
      disadvantaged urban women.
AB  - This research evaluated a motivation-based HIV risk reduction intervention for
      economically disadvantaged urban women. Participants completed a survey that
      assessed HIV-related knowledge, risk perceptions, behavioral intentions, sexual
      communication, substance use, and risk behavior. A total of 102 at-risk women
      (76% African American) were randomly assigned to either the risk reduction
      intervention or to a waiting list. Women were reassessed at 3 and 12 weeks.
      Results indicated that treated women increased their knowledge and risk
      awareness, strengthened their intentions to adopt safer sexual practices,
      communicated their intentions with partners, reduced substance use proximal to
      sexual activities, and engaged in fewer acts of unprotected vaginal intercourse.
      These effects were observed immediately, and most were maintained at follow-up.

PMID- 9256556
TI  - Acute and chronic distress and posttraumatic stress disorder as a function of
      responsibility for serious motor vehicle accidents.
AB  - In this study on the effects of attributions of responsibility for traumatic
      events, stress, coping, and symptoms of posttraumatic stress disorder (PTSD) were
      measured, including intrusive thoughts among 130 victims of serious motor vehicle
      accidents (MVAs) 14-21 days and 3, 6, and 12 months after their accident. MVA
      victims and 43 control participants were categorized by accident and attribution
      of responsibility for their accidents (self-responsible, other-responsible, and
      control). Although initially all MVA victims reported higher levels of intrusive
      thoughts and were more likely to meet criteria for PTSD diagnoses, only other
      responsible participants continued to demonstrate increased distress 6 and 12
      months postaccident. Self-responsible participants used more self-blame coping
      than other-responsible participants, although within the self-responsible group,
      use of self-blame was associated with more distress.

PMID- 9256557
TI  - Response to cognitive-behavioral therapy in depression: effects of pretreatment
      cognitive dysfunction and life stress.
AB  - Response to cognitive-behavioral therapy (CBT) for depression is variable and the
      factors that account for differences in response are not yet well established.
      Level of cognitive dysfunction and the occurrence of negative life stress have
      been theorized as patient variables, which may account for differences in
      response to CBT. The relationship between response to CBT and the interaction of
      cognitive dysfunction with negative life events was examined in a sample of 53
      depressed outpatients. Overall, there was little support for the prediction of a
      difference in acute outcome between patients with or without pretreatment
      cognitive dysfunction and negative stressors.

PMID- 9256558
TI  - Information processing and affective distress in osteoarthritis patients.
AB  - The relationship between affective distress and chronic illnesses is well
      recognized. Recent research has focused on depressive symptomatology among
      patients with chronic pain. The present study was conducted to (a) examine
      depressive information processing in osteoarthritis patients and (b) assess
      whether the presence of somatic items on a depression measure would affect the
      observed associations between information processing and affective distress in
      arthritis patients. A group of 40 osteoarthritis patients was assessed using the
      Beck Depression Inventory, and a non-self-report measure of depressive self
      schemas. Results suggest that observed depressive cognitive structures appear to
      be better differentiated by a nonsomatic measure of affective distress and that
      individuals selectively process information to fit the parameters of their
      currently active self-schema.

PMID- 9256559
TI  - The therapeutic alliance in psychodynamic-interpersonal and cognitive-behavioral
      therapy.
AB  - The quality of the therapeutic alliance was compared in sessions of psychodynamic
      interpersonal and cognitive-behavioral therapy, and the alliance's relationship
      to various session impacts was investigated. As part of the Sheffield
      Psychotherapy Project 2 (D. A. Shapiro, M. Barkham, A. Rees, G. E. Hardy, S.
      Reynolds, & M. Startup, 1994), 57 clients diagnosed with major depression
      received 16 sessions of either psychodynamic-interpersonal or cognitive
      behavioral therapy. Coders used the Working Alliance Inventory to rate 1 high
      impact and 1 low-impact session from each client. Results indicated significantly
      greater alliance scores for cognitive-behavioral therapy sessions on the whole.
      Also, for the samples as a whole, high-impact sessions were characterized by
      higher alliance scores than those for low-impact sessions, and alliance was
      positively related to therapists' ratings of session depth and smoothness and to
      clients' ratings of mood.

PMID- 9256560
TI  - The therapeutic alliance and its relationship to alcoholism treatment
      participation and outcome.
AB  - The relationship between the therapeutic alliance and treatment participation and
      drinking outcomes during and after treatment was evaluated among alcoholic
      outpatient and aftercare clients. In the outpatient sample, ratings of the
      working alliance, whether provided by the client or therapist, were significant
      predictors of treatment participation and drinking behavior during the treatment
      and 12-month posttreatment periods, after a variety of other sources of variance
      were controlled. Ratings of the alliance by the aftercare clients did not predict
      treatment participation or drinking outcomes. Therapists ratings of the alliance
      in the aftercare sample predicted only percentage of days abstinent during
      treatment and follow-up. The results document the independent contribution of the
      therapeutic alliance to treatment participation and outcomes among alcoholic
      outpatients.

PMID- 9256561
TI  - Toward terminological, conceptual, and statistical clarity in the study of
      mediators and moderators: examples from the child-clinical and pediatric
      psychology literatures.
AB  - Numerous recent attempts to identify mediated and moderated effects in child
      clinical and pediatric research on child adjustment have been characterized by
      terminological, conceptual, and statistical inconsistencies. To promote greater
      clarity, the terms mediating and moderating are defined and differentiated.
      Recommended statistical strategies that can be used to test for these effects are
      reviewed (i.e., multiple regression and structural equation modeling techniques).
      The distinction between mediated and indirect effects is also discussed. Examples
      of troublesome and appropriate uses of these terms in the child-clinical and
      pediatric psychology literatures are highlighted.

PMID- 9256562
TI  - Biofeedback treatment for pediatric migraine: prediction of treatment outcome.
AB  - Despite a growing number of studies showing good effectiveness of
      nonpharmacological treatments such as thermal biofeedback (TBF) for pediatric
      migraine, little is known about psychosocial variables that might be predictive
      of treatment outcome. The identification of predictors appears especially
      important when children are treated in a home-based treatment format that tends
      to be somewhat less effective than a therapist-administered treatment. A total of
      32 children between the ages 8 and 16 years completed a home-based TBF treatment
      program with treatment outcome being of similar magnitude as previously reported
      in the literature. Multiple regression analysis revealed externalizing behavior
      tendencies, initial level of psychosomatic complaints, and the child's age to be
      highly predictive of outcome, whereas dimensions of family functioning failed to
      exert a direct influence. The implications of these findings for the development
      and evaluation of future treatment programs are discussed.

PMID- 9256563
TI  - Gender differences in depressive symptoms in adolescence: comparison of national
      samples of clinically referred and nonreferred youths.
AB  - Gender differences in depressed mood, a syndrome of mixed anxiety-depression, and
      an analogue of major depressive disorder were compared in parents' and
      adolescents' reports in 2 large, demographically matched national samples of
      clinically referred and nonreferred adolescents. Referral status accounted for
      the greatest share of the variance in these problems. Gender differences were
      moderate in size and consistent in referred youths, with referred girls scoring
      higher than referred boys on all measures, whereas gender differences in
      nonreferred adolescents were either nonsignificant or small in magnitude. Gender
      differences were also larger in magnitude in adolescents' self-reports than in
      parents' reports. The interaction of age and gender was nonsignificant in all
      analyses. Implications for understanding the extent of gender differences in
      adolescents' depressive symptoms are highlighted.

PMID- 9256564
TI  - Prevention and early intervention for anxiety disorders: a controlled trial.
AB  - The Queensland Early Intervention and Prevention of Anxiety Project evaluated the
      effectiveness of a cognitive-behavioral and family-based group intervention for
      preventing the onset and development of anxiety problems in children. A total of
      1,786 7- to 14-year-olds were screened for anxiety problems using teacher
      nominations and children's self-report. After recruitment and diagnostic
      interviews, 128 children were selected and assigned to a 10-week school-based
      child- and parent-focused psychosocial intervention or to a monitoring group.
      Both groups showed improvements immediately postintervention. At 6 months follow
      up, the improvement maintained in the intervention group only, reducing the rate
      of existing anxiety disorder and preventing the onset of new anxiety disorders.
      Overall, the results showed that anxiety problems and disorders identified using
      child and teacher reports can be successfully targeted through an early
      intervention school-based program.

PMID- 9256565
TI  - Attributions for child behavior in parents of children without behavior disorders
      and children with attention deficit-hyperactivity disorder.
AB  - Attributions for and reactions to inattentive-overactive, oppositional-defiant,
      and prosocial child behaviors were compared in 52 parents of children with
      attention deficit-hyperactivity disorder (ADHD) and 42 parents of children
      without behavior disorders. Parent attributions and reactions elicited using
      written descriptions of child behavior, behaviors the parent recalled his or her
      own child displaying, and videotaped clips of the parent's own child's behavior
      all revealed a similar pattern. Compared with parents of children without
      behavior disorders, parents of children with ADHD saw inattentive-overactive and
      oppositional defiant behaviors as more internally caused, less controllable by
      the child, and more stable; and they had more negative reactions to such
      behaviors. For prosocial child behaviors, parents of children with ADHD rated the
      causes as less internal and less stable than control parents did.

PMID- 9256566
TI  - Thresholds and tolerance of physical pain in suicidal and nonsuicidal
      adolescents.
AB  - It was hypothesized that suicidal inpatient adolescents (n = 38) will exhibit a
      higher tolerance for physical pain than nonsuicidal inpatients (n = 29) and
      control participants (n = 34). Participants provided self-reports of
      hopelessness, dissociation, suicidal tendencies, depression, and anxiety and were
      administered a series of thermal pain stimuli by means of a Thermal Sensory
      Analyzer (TSA). The suicidal participants significantly differed from the 2
      controls in pain thresholds and tolerance and in most self-report measures, even
      after controlling for motivation, medication, diagnosis, and length of
      hospitalization. Significant correlations were found between pain measures and
      self-report measures. The results were discussed in terms of the role that body
      experiences play in suicidal behavior.

PMID- 9256567
TI  - Predictors of risk for different stages of adolescent smoking in a biracial
      sample.
AB  - This investigation was designed to identify the risk factors associated with
      different stages of cigarette use in a large biracial adolescent sample. A
      questionnaire assessing smoking habits and variables thought to be related to
      smoking was administered to 6,967 7th graders. Analysis revealed that the best
      predictor of experimentation with cigarettes was the perception that they were
      easily available. Regular smoking appeared to be heavily influenced by cost.
      Social influences contributed to both experimental and regular smoking, but the
      impact of social models varied with ethnicity and gender. Analysis further
      revealed that weight-related variables were closely tied to regular smoking.
      Implications of the findings for smoking prevention programs are discussed.

PMID- 9256568
TI  - Nicotine patch and self-help video for cigarette smoking cessation.
AB  - A total of 424 smokers were randomized in a 2 x 2 factorial experiment. A
      pharmacologic factor contained 2 levels: transdermal nicotine path (TNP; 21 mg)
      and placebo. A self-help behavioral treatment factor contained 2 levels: video
      enhanced self-help treatment manual and self-help treatment manual only. At 2
      months, TNP produced a higher level of abstinence (36%) than placebo (20%), p <
      .001. No other comparison was significant. In secondary analyses, (at 2 months)
      and compliance with patch treatment regimen (at 2, 6, and 12 months) were
      associated with less relapse. Although nicotine replacement therapy has improved
      our ability to produce smoking cessation, the production of sustained, longer
      term abstinence remains an elusive goal.

PMID- 9256570
TI  - Behavioral Self-Control Program for Windows: results of a controlled clinical
      trial.
AB  - Forty nonalcoholic heavy drinkers were randomly assigned to receive a computer
      based version of behavioral self-control training either immediately after
      pretreatment assessment or after a 10-week waiting period. Results at each of 3
      follow-ups strongly support the study hypotheses. Participants in the immediate
      treatment group significantly reduced their drinking relative to their
      pretreatment levels and relative to those in the delayed treatment condition at
      the initial follow-up, 10 weeks after the pretreatment assessment. The delayed
      group did not change their drinking behaviors during this period of time.
      However, they significantly reduced their drinking by the second follow-up
      conducted after they received training. At the 12-month follow-up, participants
      maintained the gains they had achieved during treatment. There were no
      interactions involving participant ethnicity or gender. Although use of other
      drugs was not specifically addressed, such use did not increase, and there was
      some evidence of a decline.

PMID- 9256569
TI  - Natural classes of treatment response.
AB  - This study examines an approach to identifying patterns of treatment response
      over time. Treatment response profiles are identified by cluster analyzing a
      repeated measure of patient performance collected at intervals during treatment.
      The procedure is demonstrated in Study 1 using monthly urinalysis results of 103
      patients entering methadone maintenance treatment. The internal, external, and
      face validities of derived treatment response profiles are evaluated. A logistic
      regression model predicting treatment response is then constructed from intake
      variables found to correspond with the treatment response profiles. Study 2
      replicates the procedures on an independent sample. Treatment response profiles
      facilitate the analysis of treatment response offering advantages over common
      measures of treatment outcome, such as performance at follow-up, change in
      performance from treatment entry to follow-up, or performance summed across
      treatment.

PMID- 9256571
TI  - Clients' expectancies and their relationship to pretreatment symptomatology and
      outcome of cognitive-behavioral group treatment for social phobia.
AB  - The present study examined the expectancies of clients with social phobia that
      they would benefit from cognitive-behavioral group treatment. Lower expectancies
      for positive outcome were related to greater severity of social phobia, duration
      of social phobia, and depression. Lower expectancies were also reported by
      individuals with the generalized subtype of social phobia, but expectancies were
      not further influenced by the presence of other Axis I disorders. Expectancy
      ratings did not differ between clients who dropped out of treatment and those who
      did not, but, after pretreatment severity of social phobia was accounted for,
      expectancies significantly predicted improvement among treatment completers.
      Clients' expectancy beliefs may be an important factor to address in the
      prediction of who will benefit from a cognitive-behavioral treatment, even when
      that treatment has demonstrated specific efficacy.

PMID- 9256572
TI  - Use and abuse of the Children's Depression Inventory.
AB  - This study investigated current uses of the Children's Depression Inventory
      (CDI), a frequently cited self-report measure for children's depressive
      symptomatology. Recently published studies of "childhood depression" were
      reviewed: Half of them used the CDI. Of these studies, 68% did not use a clinical
      or structured interview to determine diagnostic status. When the CDI was used
      alone to assess depressive symptoms, 44% of studies referred to high CDI scorers
      as "depressed" without providing a clear cautionary statement (i.e., either
      stating that the CDI cannot be used to diagnose depression or clarifying
      limitations regarding generalization of findings from a nonclinical to a clinical
      sample). These results are similar to those previously published regarding the
      Beck Depression Inventory, and they suggest a need for caution in the
      administration and interpretation of results from self-report inventories for
      children's depressive symptoms.

PMID- 9256574
TI  - More on melatonin.

PMID- 9256573
TI  - Brief treatment of mild-to-moderate child depression using primary and secondary
      control enhancement training.
AB  - Elementary school children with mild-to-moderate depressive symptoms were
      randomly assigned to a control group or an 8-session Primary and Secondary
      Control Enhancement Training program. The program focused on (a) primary control
      (changing objective conditions to fit one's wishes; e.g., through activity
      selection and goal attainment) and (b) secondary control (changing oneself to
      buffer the impact of objective conditions; e.g., altering depressogenic thinking,
      practicing mood-enhancing cognitions). At immediate posttreatment and 9-month
      follow-up, the treatment group showed greater reductions than the control group
      in depressive symptomatology on the Children's Depression Inventory and the
      Revised Children's Depression Rating Scale, and treated children, more than
      controls, shifted from above to within the normal range on both measures. Future
      research is needed to test treatment effects with severely depressed youths.

PMID- 9256575
TI  - More on melatonin.

PMID- 9256576
TI  - Diet therapy.

PMID- 9256577
TI  - Methylphenidate and the immune system.

PMID- 9256578
TI  - "Standard of care" for MDD.

PMID- 9256579
TI  - Medication-induced psychotic reaction.

PMID- 9256580
TI  - Medication-induced seizures.

PMID- 9256581
TI  - More on nonaffective seasonality.

PMID- 9256582
TI  - Learning disorders with a special emphasis on reading disorders: a review of the
      past 10 years.
AB  - OBJECTIVE: To review the past 10 years of clinical and research reports on
      learning disorders. METHOD: The most common and best-researched type of learning
      disorder is reading disability, which is the focus of this review. A selective
      review of the literature from Psychological Abstracts and Index Medicus from 1985
      to the present was conducted. This review focused on conceptual and
      methodological issues, current assessment practices, epidemiology, correlates of
      brain function, biological factors, predictors of reading achievement, core
      deficits, comorbidity reading development and instructional approaches,
      treatment, and outcome. RESULTS: Definitional issues, still unresolved, bedevil
      the field with the debate between those for and those against discrepancy
      definitions of reading disabilities. Nevertheless considerable progress has been
      made. Phonological processing problems are now considered the main core deficit
      responsible for reading disabilities. Correlates of brain function and possible
      genetic factors are noted. Comorbidity with externalizing and internalizing
      disorders is described, and some theories for the overlap are identified. Studies
      on the comorbidity with internalizing disorders are lacking. Good assessment
      practice and promising approaches to remediation are identified. Unless a
      concurrent disorder is present, the use of medication for the treatment of
      reading disabilities should be considered experimental. Favorable outcomes are
      dependent on initial severity and a supportive home and school environment.
      CONCLUSIONS: Much progress has been made in our understanding of learning
      disabilities, especially in reading disabilities. Resolution of definitional and
      conceptual issues will greatly assist research into assessment, treatment, and
      long-term outcome of learning disabilities with and without concurrent
      psychiatric disorders. Further research into the nature, extent, and correlates
      of comorbid learning disabilities and their treatment is much needed.

PMID- 9256583
TI  - Gender differences in ADHD: a meta-analysis and critical review.
AB  - OBJECTIVE: To quantitatively review and critically evaluate literature examining
      gender differences in attention-deficit hyperactivity disorder (ADHD). METHOD: A
      meta-analysis of relevant research based on 18 studies meeting inclusion criteria
      was performed. Domains evaluated included primary symptomatology, intellectual
      and academic functioning, comorbid behavior problems, social behavior, and family
      variables. RESULTS: Gender differences were not found in impulsivity, academic
      performance, social functioning fine motor skills, parental education, or
      parental depression. However, compared with ADHD boys, ADHD girls displayed
      greater intellectual impairment, lower levels of hyperactivity, and lower rates
      of other externalizing behaviors; it was not possible to evaluate the extent to
      which referral bias affected these findings. Some gender differences were clearly
      mediated by the effects of referral source; among children with ADHD identified
      from nonreferred populations, girls with ADHD displayed lower levels of
      inattention, internalizing behavior, and peer aggression than boys with ADHD,
      while girls and boys with ADHD identified from clinic-referred samples displayed
      similar levels of impairment on these variables. CONCLUSIONS: The need for future
      research examining gender differences in ADHD is strongly indicated, with
      attention to methodological limitations of the current literature, including the
      potential confounding effects of referral bias, comorbidity, developmental
      patterns, diagnostic procedures, and rater source.

PMID- 9256584
TI  - Is comorbidity with ADHD a marker for juvenile-onset mania?
AB  - OBJECTIVE: To compare the characteristics and correlates of mania in referred
      adolescents and to determine whether attention-deficit hyperactivity disorder
      (ADHD) is a marker of very early onset mania. METHOD: From 637 consecutive
      admissions, 68 children (< or = 12 years) and 42 adolescents (> 13 years) who
      satisfied criteria for mania were recruited. These were compared with the 527
      nonmanic referrals and 100 normal controls. RESULTS: With the exception of
      comorbidity with ADHD, there were more similarities than differences between the
      children and adolescents with mania in course and correlates. There was an
      inverse relationship between the rates of comorbid ADHD and age of onset of
      mania: higher in manic children intermediate in adolescents with childhood-onset
      mania, and lower in adolescents with adolescent-onset mania. CONCLUSIONS: ADHD is
      more common in childhood-onset compared with adolescent-onset cases of bipolar
      disorder, suggesting that in some cases, ADHD may signal a very early onset of
      bipolar disorder. Clinical similarities between the child- and adolescent-onset
      cases provide evidence for the clinical validity of childhood-onset mania.

PMID- 9256585
TI  - Parent-assisted transfer of children's social skills training: effects on
      children with and without attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: Previous research has demonstrated that peer rejection is a
      significant part of the clinical presentation of many children with attention
      deficit hyperactivity disorder (ADHD). Outcome studies of treatment interventions
      have typically failed to show generalization of treatment gains to the home and
      classroom. This has been especially true for children who have comorbid
      oppositional defiant disorder (ODD). The present study was intended to
      demonstrate generalization of an outpatient social skills training program when
      parents were trained in skills relevant to their child's social adjustment.
      METHOD: Thirty-five children with ADHD and 14 children without ADHD were given 12
      sessions of treatment (treatment group). Outcome was compared with 12 children
      with ADHD and 12 children without ADHD who were on a waitlist for treatment
      (waitlist group). Nineteen children with ODD were in the treatment group and five
      in the waitlist. Stimulant medication was prescribed for all children with ADHD.
      RESULTS: Subjects with ADHD showed improvement comparable with that of subjects
      without ADHD on all teacher- and parent-reported measures of peer adjustment and
      social skills, except teacher-reported withdrawal. Children with ODD had outcome
      comparable with that of children without ODD. Effect sized ranged from 0.93 to
      1.34 indicating that the average treatment group subject was better off than
      83.4% of waitlist subjects on outcome measures. CONCLUSIONS: The present results
      suggest that children with ADHD are best heiped by a combination of social skills
      training for themselves, collateral training for their parents and stimulant
      medication.

PMID- 9256586
TI  - Comorbidity in ADHD: implications for research, practice, and DSM-V.
AB  - OBJECTIVE: Since the introduction of DSM-III/III-R, clinicians and investigators
      have shown increasing interest in the study of conditions comorbid with attention
      deficit hyperactivity disorder (ADHD). Better understanding ADHD comorbidity
      patterns is needed to guide treatment, research and future classification
      approaches. METHOD: The ADHD literature from the past 15 years was reviewed to
      (1) explore the most prevalent patterns of ADHD comorbidity; (2) examine the
      correlates and longitudinal predictors of comorbidity; and (3) determine the
      extent to which comorbid patterns convey unique information concerning ADHD
      etiology, treatment and outcomes. To identify potential new syndromes, the
      authors examined comorbid patterns based on eight validational criteria. RESULTS:
      The largest available body of literature concerned the comorbidity with ADHD and
      conduct disorder/aggression, with a substantially smaller amount of data
      concerning other comorbid conditions. In many areas the literature was sparse,
      and pertinent questions concerning comorbidity patterns remain unexplored.
      Nonetheless available data warrant the delineation of two new subclassifications
      of ADHD: (1) ADHD aggressive subtype, and (2) ADHD, anxious subtype. CONCLUSIONS:
      Additional studies of the frequency of comorbidity and associated factors are
      greatly needed to include studies of differential effects of treatment of
      children with various comorbid ADHD disorders, as well as of ADHD children who
      differ on etiological factors.

PMID- 9256587
TI  - Posttraumatic symptomatology in children and adolescents after an industrial
      fire.
AB  - OBJECTIVE: This investigation evaluated the extent and nature of posttraumatic
      symptomatology (PTS) in children and adolescents 9 months after an industrial
      fire at the imperial Foods chicken-processing plant in Hamlet, North Carolina,
      caused extensive loss of life. METHOD: Using a PTS self-report measure plus self-
      and teacher reports of comorbid symptoms the authors surveyed 1,019 fourth- to
      ninth-grade students in the community where the fire occurred. RESULTS: Three
      factors comprising PTS were identified: reexperiencing, avoidance and
      hyperarousal. Reexperiencing and avoidance were positively correlated;
      hyperarousal proved weakly correlated with reexperiencing, perhaps because
      exposure was largely indirect. Using a T score cutoff of 65 on the reexperiencing
      factor as indicative of PTS 9.7% of subjects met criteria for PTS; 11.9% met
      criteria for posttraumatic stress disorder (PTSD) using DSM-III-R PTSD criteria.
      Degree of exposure was the most powerful predictor of PTS. Race (African
      American) and gender (female) posed significant risk factors for PTS. Self
      reported internalizing symptoms and teacher-reported externalizing symptoms were
      positively predicted by intercurrent PTS, and independently of PTS, by degree of
      exposure. Comorbid symptoms showed interesting interactions with exposure, race,
      and gender. Lack of self-attributed personal efficacy predicted PTS but did not
      moderate the effects of race or gender on PTS risk. CONCLUSIONS: This study,
      which used a population-based sampling strategy, strengthens and extends findings
      from earlier literature on pediatric PTSD in showing that (1) PTS and comorbid
      internalizing and externalizing symptoms rise in direct proportion to degree of
      exposure; (2) gender and race show variable effects on risk for PTS and comorbid
      symptoms; and (3) comorbid symptoms are positively correlated with PTS and may
      represent primary outcomes of traumatic exposure in their own right.

PMID- 9256588
TI  - Symptomatology and adaptive functioning for children exposed to normative
      stressors, dog attack, and parental violence.
AB  - OBJECTIVE: To examine and identify predictors of posttraumatic symptomatology and
      adaptive functioning of children exposed to single and repetitive adverse events
      that varied in severity. METHOD: A sample of 86 patients and their children, aged
      4 to 9 years, were interviewed after three types of adverse experiences;
      repetitive exposure to parental violence, a dog attack, or a milder stressor. The
      PTSD Reaction Index, Child Dissociative Checklist, and Child Behavior Checklist
      were used. RESULTS: Trauma symptoms were greater for the first two groups,
      younger children, and girls. Gender effects were most evident in the dog attack
      group and depended on type of symptoms and informant. Supportiveness in the
      parenting relationship aided prediction of both trauma symptoms and adjustment.
      CONCLUSIONS: Children appear to experience elevated posttraumatic stress disorder
      symptomatology after both single and repetitive adverse events that are
      potentially life-threatening. A positive parental relationship is associated with
      fewer symptoms and better adaptive functioning. The mechanisms through which this
      support interacts with behavioral and physiological systems to facilitate better
      regulation await further research.

PMID- 9256589
TI  - Effects of war trauma on Cambodian refugee adolescents' functional health and
      mental health status.
AB  - OBJECTIVE: To measure the effect of war trauma on the functional health and
      mental health status of Cambodian adolescents living in a refugee camp on the
      Thai-Cambodian border. METHOD: A multistage probability sample identified 1,000
      households in the camp known as Site Two. Interviews were conducted in each
      household with randomly selected adults 18 years of age and older. All
      adolescents aged 12 and 13 years old, along with one parent were interviewed. One
      hundred eighty-two adolescents (94 girls, 88 boys) and their parents
      participated. Culturally sensitive instruments were used including Cambodian
      versions of the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR).
      RESULTS: Parents and adolescents reported the latter having experienced high
      levels of cumulative trauma, especially lack of food, water, and shelter. Mean
      Total Problem scores were in ranges similar to those of adolescents receiving
      clinical care in the United States, Netherlands, and Israel. Nearly 54% (53.8%)
      had Total Problem scores in the clinical range by parent report on the CBCL and
      26.4% by adolescent report on the YSR. The most commonly reported symptoms were
      somatic complaints social withdrawal attention problems, anxiety, and depression.
      The dose-effect relationship between cumulative trauma and symptoms was strong
      for parent reporting on the CBCL; the subscales on both the YSR and CBCL for
      Anxious/Depressed and Attention Problems revealed dose-effect associations. Dose
      effect relationships between cumulative trauma and social functioning or health
      status were lacking. CONCLUSION: The high levels of emotional distress in this
      population of Cambodian adolescents and corresponding dose-effect relationships
      reveal the important negative psychosocial impact of violence on Cambodian
      adolescents. Lack of findings related to physical health status and the presence
      of positive social functioning of many youths should not deter health care
      providers and public health officials from diagnosing and treating underlying
      high levels of psychological distress.

PMID- 9256590
TI  - Relationship of childhood sexual abuse and eating disorders.
AB  - OBJECTIVE: To review the literature that has examined the relationship between
      childhood sexual abuse and the eating disorders. METHOD: Each of the five authors
      reviewed all identified empirical studies to be certain that inclusion/exclusion
      criteria were met. Two teams of raters then independently reviewed each study to
      determine whether it supported any of a series of six hypotheses that had been
      tested in this literature. RESULTS: This review indicates that childhood sexual
      abuse is a nonspecific risk factor for bulimia nervosa, particularly when there
      is psychiatric comorbidity. There is some indication that childhood sexual abuse
      is more strongly associated with bulimic disorders than restricting anorexia, but
      it does not appear to be associated with severity of the disturbance. CONCLUSION:
      Childhood sexual abuse is a risk factor for bulimia nervosa with significant
      comorbidity. Further study of the nature of this relationship is warranted.

PMID- 9256591
TI  - Partial eating disorders in a community sample of female adolescents.
AB  - OBJECTIVES: To evaluate the validity of two definitions of partial eating
      disorders, the Eating Attitudes Test (EAT) and a combination of the EAT and
      relevant criteria of the DSM-III-R, and to examine their association with factors
      related to anorexia nervosa and bulimia nervosa. METHOD: Questionnaires on eating
      behaviors, depression, obsessionality, and impulsivity were distributed to 534
      female high school students. Demographic, psychosocial, and physical parameters
      and the subjects' height and weight were also recorded. RESULTS: EAT scores
      revealed maladaptive behaviors in 18% of the subjects: the combination of the EAT
      and DSM-III-R criteria identified 20.8% of the subjects as having partial
      anorexia nervosa and 11.3% as having partial bulimia nervosa. Both definitions
      were significantly associated with risk factors for clinical eating disorders:
      high weight, weight fluctuations, dieting, menstrual disturbances, high level of
      depression and obsessionality, and preoccupation with eating in the family.
      Partial bulimics fared worse on most of these parameters. Partial anorectics were
      not more psychologically distressed than normal subjects. CONCLUSIONS: The
      validity of both definitions of partial eating disorders is supported by their
      similar and significant associations with known risk factors for the development
      of the clinical syndromes. Partial bulimics are similar to patients with bulimia
      nervosa in the level of many eating-related disturbances and in depression,
      obsessionality, and impulsivity. Partial anorectics, like anorectic patients in
      clinical settings, tend to minimize their problems. The relevance of partial
      eating disorders to the later development of the full-blown clinical entity is
      still not established.

PMID- 9256592
TI  - Case study: chewing gum treatment of rumination in an adolescent with an eating
      disorder.
AB  - Rumination occurs frequently in children and adolescents with eating disorders,
      but few studies or case reports consider rumination an associated symptom. Fewer
      address related treatment issues. The authors describe successful treatment of
      rumination in a 16-year-old female adolescent using postmeal chewing gum.
      Rumination should be considered in youngsters with bulimia or anorexia nervosa,
      and approaches to its treatment should be studied.

PMID- 9256593
TI  - Case study: an infection-triggered, autoimmune subtype of anorexia nervosa.
AB  - OBJECTIVE: Certain cases of anorexia nervosa (AN) may be similar to the recently
      described subtype of childhood-onset obsessive-compulsive disorder hypothesized
      to be one of the pediatric infection-triggered autoimmune neuropsychiatric
      disorders (PITANDs). METHOD: Three clinical cases are reported. The first patient
      is a 12-year-old boy whose AN worsened acutely after a group A beta-hemolytic
      streptococcal (GABHS) infection. His symptoms were alleviated after antibiotic
      treatment. Two other patients with possible PITANDs-related AN are described.
      RESULTS: An infection-triggered process may contribute to the pathogenesis of a
      subtype of AN. CONCLUSIONS: Future research is needed to explore the nature of
      PITANDs and their relationship with AN.

PMID- 9256595
TI  - Moralization of attachment: a fourth domain of conscience functioning.
AB  - OBJECTIVES: To define discrete developmental levels of understanding regarding
      the ways in which normal children and adolescents link remembered and current
      attachment experiences to their moral belief system and to study the correlation
      between this progression and previously identified stages of conscience
      conceptualization. METHOD: Using the moralization of attachment section from the
      semistructured Stilwell Conscience Interview, 132 normal volunteers between the
      ages of 5 and 17 years were individually interviewed. Analysis of the interviews
      resulted in five levels of understanding. RESULTS: By analyses of variance and
      covariance, the five attachment levels showed significant correlation with the
      five conceptualization stages. Conceptualization stage showed a stronger
      correlation than age. CONCLUSIONS: In normal development, moralization of
      attachment is a domain of conscience functioning which follows a five-level
      hierarchical developmental progression; first, the child's sense of security and
      empathic responsiveness become paired with a sense of moral obligation; caretaker
      rules are then incorporated; an understanding of how empathy modifies strict rule
      following develops; idols and ideals are chosen that reflect earlier learning in
      attachment relationships; finally, a visualization of the self as moral standard
      bearer or teacher unfolds.

PMID- 9256594
TI  - Intergenerational transmission of parental bonding among women.
AB  - OBJECTIVE: To examine the transmission of parental bonding style from mothers to
      daughters. METHOD: Sixty mothers and their 69 daughters were independently
      assessed over the course of a 10-year follow-up. The Parental Bonding instrument
      was administered to both mothers and daughters to assess their own childhood
      parenting. Depression was assessed using the Schedule for Affective Disorders and
      Schizophrenia-Lifetime version. Temperament was assessed through self-report on
      the Dimensions of Temperament Survey. A series of logistic regressions were run
      to predict daughter report of maternal affectionless control, taking into account
      maternal and daughter depression status, temperament, and socioeconomic status.
      RESULTS: The intergenerational transmission of parental bonding among women was
      shown to be independent of maternal depression, daughter depression, maternal
      temperament, daughter temperament, and socioeconomic status. CONCLUSION: Given
      the previously established association between parental bonding style and
      depression in offspring, the sturdiness of the intergenerational transmission of
      parental bonding among women suggests the routine clinical assessment of maternal
      bonding style.

PMID- 9256596
TI  - Psychological defense styles in late adolescence and young adulthood: a follow-up
      study.
AB  - OBJECTIVE: The aims of this follow-up study were to examine in both sexes (1) the
      stability of defense styles from late adolescence to early adulthood and (2) the
      ability of adolescent defense styles to predict later psychiatric symptoms.
      METHOD: Defense styles were examined using the Defense Style Questionnaire. Five
      hundred sixteen high school students (337 females and 179 males) completed the
      questionnaire at 15 through 19 years of age, and again 5 years later. In the
      follow-up examination the General Health Questionnaire was used to assess
      psychiatric disturbance. RESULTS: Neurotic and immature defense style scores
      decreased significantly in both sexes, whereas mature defense style scores did
      not change significantly. Females had significantly higher neurotic defense style
      scores than males in both late adolescence and young adulthood. Psychiatric
      disturbance at follow-up was associated positively with baseline immature defense
      style scores in both sexes, and negatively with baseline mature defense style
      scores in females. CONCLUSIONS: Development of defenses was apparent as a
      decrease in neurotic and immature defense style scores. In both sexes, immaturity
      of defenses in late adolescence predicted psychiatric symptoms in young
      adulthood.

PMID- 9256597
TI  - [Argentina Society of Hypertension. 4th Argentina Congress of Hypertension.
      Buenos Aires, 21-23 November 1996. Abstracts].

PMID- 9256598
TI  - Research raises questions, but doesn't always answer them.

PMID- 9256599
TI  - Patient referrals.

PMID- 9256600
TI  - An ounce of protection.

PMID- 9256601
TI  - Silly season.

PMID- 9256602
TI  - Protecting dental services for people with developmental disabilities. The impact
      of Medicaid managed care.

PMID- 9256604
TI  - Into the heart of Africa.
AB  - Dentistry is a profession that enables us to combine adventure with the useful.
      By using our skill and knowledge we can, at least on a limited level, contribute
      to improving the health of people in third world countries. This article relates
      a dental volunteer trip into the heart of Africa. The rewards of this type of
      volunteer dentistry are lifelong memories and great satisfaction.

PMID- 9256603
TI  - Disinfection of impressions. Methods and effects on accuracy.
AB  - An understanding of the methods and mechanics of sterilization and disinfection
      is necessary to prevent bacterial cross-contamination. Since sterilization of
      impressions is not possible, because of the high temperature and time needed,
      disinfection is the method of choice. The most effective means of disinfecting
      impressions is to immerse them in disinfectant solution for 30 minutes. Most
      hydrophobic impression materials exhibit minimal distortion when disinfected in
      this manner. Irreversible hydrocolloid (alginate) and hydrophilic silicones
      distort when immersed and can be disinfected by spraying and placing in a sealed
      plastic bag for manufacturer's recommended time. Internal disinfection (replacing
      water with disinfectant before impression taking) is the method of choice for
      alginate, since it allows immediate pouring of the impression after removal from
      the oral cavity.

PMID- 9256605
TI  - Buy now ... pay later.

PMID- 9256606
TI  - Medicaid audits and the dentist.
AB  - Dental Medicaid, an essential health adjunct for many indigent people, is seen
      from the standpoint of a New York State dentist auditor. A few professionals may
      be abusing the system to the detriment of the majority. How to follow the rules
      and avoid costly audits.

PMID- 9256608
TI  - [Serum levels and in vitro production of IL-5 in children with bronchial asthma].
AB  - IL-5 play important roles in inflammatory responses in bronchial asthma, but
      little is known about serum levels and in vitro production of IL-5 in childhood
      bronchial asthma. We further examined serum IL-5 levels in children with
      bronchial asthma and the controls. IL-5 in serum was detected in all of asthmatic
      and disease-free individuals. Its values during asthma exacerbation were
      significantly higher than during remission of asthma. Serum IL-5 values did not
      significantly differ among groups divided by asthma severity. We studied IL-5
      production by peripheral blood mononuclear cells cultured with or without
      Dermatophagoides farinae (Df) in children with mite allergy. IL-5 concentrations
      in culture supernatant from after stimulation with Df were significantly higher
      than those from asthmatic patients without stimulation and from the control
      subjects. In contrast, IL-5 levels in culture media from the controls were not
      significantly different between with and without stimulation with Df. Our results
      suggest that IL-5 may play roles in the pathogenesis of bronchial asthma.

PMID- 9256607
TI  - [Cyclophosphamide pulse therapy for refractory rheumatic diseases].
AB  - We studied the efficacy of cyclophosphamide pulse therapy (CYP) for refractory
      rheumatic diseases except for lupus nephritis. Thirty-five patients were included
      in all, that is 9 patients with systemic lupus erythematosus (SLE), 10 with
      rheumatoid arthritis (RA), 7 with polymyositis/dermatomyositis (PM/DM), 2 with
      progressive systemic sclerosis (PSS), 2 with anti-phospholipid antibody syndrome
      (APS), 1 with mixed connective tissue disease (MCTD), 1 with juvenile rheumatoid
      arthritis (JRA), 1 with Behcet's disease (BD), 1 with Wegener's granulomatosis
      (WG) and 1 with allergic granulomatous angiitis (AGA). Moderate to marked
      improvement was noted in 4 patients with SLE (2 with CNS-lupus and 2 with
      vasculitis), 7 with RA (2 with interstitial pneumonia:IP, 2 with vasculitis and 2
      with refractory arthritis), 4 with PM/DM (2 with IP and 2 with refractory
      myositis), 1 PSS with IP, 2 APS with thrombocytopenia, 1 JRA with vasculitis and
      BD with CNS disturbance. On the other hand, adverse reactions were observed in 9
      out of 35 patients (25.8%). CYP should apply in the treatment for such refractory
      rheumatic diseases as CNS disturbance, vasculitis, IP and autoimmune
      thrombocytopenia.

PMID- 9256609
TI  - [Production of inflammatory markers by HepG 2 cells stimulated with monocyte
      conditioned media: the effects of corticosteroid and other immunosuppressants].
AB  - Both C-reactive protein (CRP) and serum amyloid A protein (SAA) are determined as
      an indicator of inflammation and tissue damage. We found that CRP decreased
      extremely after administration of corticosteroid but SAA did not. However, the
      mechanism of the CRP decrease by corticosteroid therapy is unclear. In this study
      we have examined the effects of some immunosuppressive drugs and cytokines on the
      production of CRP and SAA by human hepatoma cells (HepG 2). A corticosteroid
      prednisolone did not enhance the production of CRP by HepG 2 cells but enhanced
      that of SAA, which indicate that prednisolone had no direct effect on the CRP
      production. Some immunosuppressants other than corticosteroids suppressed the SAA
      production but had no effect on the CRP production. IL-1 beta induced both CRP
      and SAA production but only in the co-presence of IL-6. A cytokine IL-6 induced
      the CRP production in the presence of IL-1 beta, but did not affect the
      constitutive production of SAA. Then we have examined the cytokine production by
      monocytes stimulated by lipopolysaccharide. Prednisolone inhibited the production
      of IL-1 alpha, IL-1 beta, IL-6 and TNF alpha.

PMID- 9256610
TI  - Effective treatment with low-dose methotrexate pulses of a child of mixed
      connective tissue disease with severe myositis refractory to corticosteroid.
AB  - A 13-year-old girl with mixed connective tissue disease (MCTD) was described. She
      visited our hospital with recurrent parotid gland swelling, arthritis, and
      myositis. Sclerodactyly and Raynaud's phenomenon were also defined, and the
      laboratory findings of high titers of antinuclear antibody (speckled type),
      positive anti-RNP antibody, positive rheumatoid factor, and
      hypergammaglobulinemia suggested the diagnosis of MCTD associated with Sjogren
      syndrome. The muscle weakness and the increased levels of CK prompted us to
      examine the muscle biopsy and to perform the electromyography, both of which
      suggested severe muscle inflammation. The siarography and lip biopsy indicated
      definitively the association of Sjogren syndrome. Corticosteroid therapy
      including methyl-prednisolone pulses was started, but the effects were limited.
      The addition of low-dose methotrexate effectively lowered the levels of CK, and
      gradually improved the muscle strength. Thus, low-dose methotrexate therapy is
      recommended to the patients with MCTD who have severe myositis refractory to
      corticosteroid.

PMID- 9256611
TI  - [A fatal case of overwhelming postsplenectomy infection syndrome developing 10
      years after splenectomy].
AB  - Splenectomized patients are likely to suffer from severe infections, such as
      sepsis and meningitis. This syndrome is called overwhelming postsplenectomy
      infection (OPSI) in Europe and America. The course is rapid, the clinical
      symptoms are serious, and the prognosis is very poor. We treated one adult
      patient with OPSI syndrome that developed 10 years after splenectomy. CASE: A 26
      year-old man had undergone a splenectomy following a traffic accident 10 years
      previously. On January 7, 1996, he had diarrhea and nausea. On January 10, he
      became drowsy and presented at our hospital with multiple organ failure. He
      underwent hemodialysis and plasmapheresis because of acute renal failure and also
      received immune globulin, antibiotics and prednisolone. However, these
      medications were not effective. He died 7 hours later. We identified diplococcus
      on a blood smear, IgG 3 deficiency and a low titer of specific pneumococcal IgG 2
      antibody. The autopsy findings included bilateral acute hemorrhagic necrosis of
      the adrenal glands (Waterhouse-Friderichsen syndrome).

PMID- 9256613
TI  - [Severe left ventricular dysfunction in a patient with primary Sjogren's
      syndrome].
AB  - A 43-year-old woman was admitted to our hospital for evaluation of shortness of
      breath and palpitation on exertion. She had a 20-year history of dry mouth and a
      10-year history of recurrent pneumonia. She had been diagnosed as having primary
      Sjogren's syndrome with interstitial pneumonia at 42 years of age. On admission,
      cardiac ultrasonography revealed reduced left ventricular systolic function.
      Complications that would elicit cardiac manifestations such as viral myocarditis,
      amyloidosis, sarcoidosis, and ischemic heart disease, were excluded. Oral
      corticosteroid therapy was effective for alleviating symptoms. In this patient,
      it appears that primary Sjogren's syndrome is involved in the reduced left
      ventricular systolic function.

PMID- 9256612
TI  - [A refractory case of adult-onset Still's disease].
AB  - We report here a case of adult-onset Still's disease (AOSD), who finally
      responded to a combination of cyclophosphamide (CPA) and gold sodium thiomalate
      (GST) after two years of active disease. A 23-year-old man having continuous high
      fever with skin rash, polyarthralgia and increased serum ferritin, was diagnosed
      as AOSD, and oral corticosteroid was initially effective. His symptoms recurred
      one year later without clinical improvement to increased dosage of steroid. He
      was admitted to our hospital with pericarditis and pleural effusion but did not
      respond to either intravenous (i.v.) pulse steroid therapy, methotrexate (MTX) or
      high dose i.v. gamma-globulin. He was partly responsive to monthly i.v. injection
      of CPA, but clinical symptoms did not completely subside and hyperferritinemia
      persisted. GST, initiated in combination with CPA, however, was successful to
      induce complete remission. MTX has recently been reported to be efficacious to
      steroid-resistant AOSD, but CPA and gold compounds might be useful to refractory
      case of AOSD.

PMID- 9256614
TI  - [The clinical application of bioactive substances].

PMID- 9256615
TI  - [Effects of beta-adrenergic agonists and phosphodiesterase inhibitors on the
      outflow facility of the eye].
AB  - Changes in the outflow facility of perfused bovine eyes and in the shape of cells
      in cultured trabecular meshwork (TM) were studied after exposure to adrenergic
      drugs. Dobutamine, a selective beta 1 agonist caused confluent TM cells to change
      from their usual polygonal shape to a characteristic stellate shape. Salbutamol,
      a selective beta 2 agonist showed no effect. The phosphodiesterase (PDE)
      inhibitors, isobutylmethylxanthine (IBMX), theophylline, and caffeine were also
      very effective in producing this shape change. Epinephrine, isoproterenol,
      dobutamine or salbutamol did not increase the outflow facility, at temperatures
      of 22 degrees C or 36 degrees C, whereas theophylline, caffeine and IBMX
      increased the facility in a dose-dependent manner. The high concentrations of
      beta-adrenergic agents required to produce even a small change in outflow
      facility and the cell shape argue against the involvement of adrenergic receptor
      mediation; on the other hand, the enhancement of the effects of epinephrine by
      PDE inhibitors and a similar effect produced by cAMP suggest that the changes in
      the cell shape are produced by beta-receptor activation. The beta-adrenergic
      agents were ineffective on changing outflow facility but the PDE inhibitors were
      remarkably effective in producing both shape change and increasing facility. PDE
      inhibition has much greater influence on and around the outflow channels than
      pure beta-adrenergic agonists, at least in enucleated bovine eyes.

PMID- 9256616
TI  - [Effects of endothelin-1 on choroidal vessels--1. Study with the scleral window
      technique].
AB  - The effects of topical administration of endothelin-1 (ET-1), a potent and long
      acting vasoconstrictive peptide, on choroidal vessels were studied in albino
      rabbits. In enucleated eyes that were divided and the retinas removed, topical
      instillation of ET-1 at 5 x 10(-5)M induced remarkable constriction of choroidal
      arteries and veins. In vivo, the scleral window technique and microcinematography
      were used to study the effects of ET-1 on the choroidal arteries. The same field
      was recorded before, and 15 and 30 minutes after, instillation of 2 microliters
      of ET-1 at 5 x 10(-5)M every 5 minutes. Topical application of ET-1 did not cause
      any statistically significant change in caliber of the choroidal arteries either
      in the untreated group or in the ganglionectomy group (superior cervical
      sympathetic ganglions were removed and choroidal arteries were dilated). These
      results suggest that ET-1 acts in choroidal arteries from the retinal side in
      vitro but does not act from the scleral side in vivo.

PMID- 9256617
TI  - [Expression of basic fibroblast growth factor and fibroblast growth factor
      receptor 1 in the experimental retinal vein occlusion model].
AB  - Retinal ischemia promotes retinal neovascularization. Vascular endothelial growth
      factor (VEGF) and fibroblast growth factor (FGF) are important growth factors for
      neovascularization. We did experimental retinal vein occlusion (RVO) and examined
      the expression of basic FGF and FGF receptor 1(one of the basic FGF receptors) by
      in situ hybridization. We used adult pigmented rats (Brown-Norway strain). Dye
      laser photocoagulation (577 nm) was applied to the retinal arteries and veins
      within two disc diameters of the optic nerve head to injure the retinal vessels.
      After one week, laser photocoagulation was applied to only the retinal veins to
      occlude them (RVO model). As a control, laser photocoagulation was applied to the
      posterior retina avoiding the retinal vessels. After treatment, the eyes were
      removed and 10 microns thick cryostat-cut chorioretinal section were used for in
      situ hybridization with probes as mentioned above. In the RVO model, expression
      of messenger RNA of basic FGF (b-FGF) and FGF receptor 1 increased in the inner
      nuclear layer and the inner segment of the photoreceptors, and appeared in the
      retinal vessel wall in the early stage. This shows that b-FGF and FGF receptor 1
      increased in the ischemic retina, and were produced on the retinal vessel wall.
      This suggests that b-FGF may be involved in protection, regeneration, and
      proliferation of the retinal vascular endothelial cells in retinal circulatory
      disturbance.

PMID- 9256618
TI  - [Lectin-histochemical study of early postnatal eyelid epithelium of the rat].
AB  - The glycoconjugates in neonate rat eyelids at postnatal day 0 or 1 were examined
      by lectin histochemistry. Maackia amurensis lectin II, which recognizes sialic
      acid alpha 2, 3 galactose beta 1, 3 N-acetylgalactosamine (Gal beta 1, 3 GalNAc)
      or sialic acid alpha 2, 3 galactose beta 1, 4 N-acetylglucosamine, bound to the
      cell membranes of the epithelial basal cells, suggesting that the glycoconjugates
      containing these sugar chains are present on their cell membranes. With respect
      to the binding of the Gal beta 1, 3 GalNAc-specific lectin, jacalin, whose
      binding is not inhibited by the terminal sialic acid, bound to the cell membranes
      of the epithelial basal cells, whereas peanut agglutinin, whose binding is
      inhibited by the terminal sialyl residue, did not bind to their cell membranes.
      These findings suggest that all the residues of Gal beta 1, 3 GalNAc in the
      glycoconjugates of their cell membranes are sialylated as the mature form.

PMID- 9256619
TI  - [Changes in the electroretinogram of eyes with diabetic retinopathy treated by
      vitrectomy].
AB  - Flash electroretinogram (ERG) and 30 Hz flicker ERG before and after operation
      were tested in 55 eyes of 46 patients with proliferative diabetic retinopathy who
      were treated by vitrectomy. The results were evaluated with preoperative ocular
      findings -the existence of retinal detachment, posterior vitreous detachment,
      panretinal photocoagulation (PRP) and vitreal hemorrhage and intraocular
      tamponade materials. In the group without retinal detachment, the amplitude of
      the ERG b-wave and a-wave after vitrectomy decreased significantly if PRP was not
      done before operation. In the group with retinal detachment, when retinal
      detachment was restricted to the posterior pole of the fundus, when posterior
      vitreous detachment had occurred in only a small area of the fundus, when there
      was vitreous hemorrhage or when silicone oil was injected in the operation, the
      amplitude of the ERG b-wave and a-wave decreased significantly after the
      operation. In both groups, the latency of 30 Hz flicker ERG was shortened
      significantly after vitrectomy.

PMID- 9256620
TI  - [Comparison between indocyanine green angiography and histopathological
      observations of choroidal neovascular membrane in age-related macular
      degeneration].
AB  - We classified choroidal neovascular membrane (CNM) (20 eyes) in age-related
      macular degeneration into four types (Type I: hyperfluorescence in both early and
      late phases, Type II: hyperfluorescence only in the early phase, Type III:
      hyperfluorescence only in the late phase, Type IV: virtually no hyperfluorescence
      in any phase) using indocyanine green angiography (IA). We performed surgery to
      remove CNM with these IA findings. After 17 surgically extracted specimens had
      been stained with hematoxylin-eosin and azan, they were examined by tight
      microscopy. Three other specimens were examined by electron microscopy. Type I
      showed many vascular channels, not present in the surrounding retinal pigment
      epithelium (RPE) cells, and little fibrous tissue. Type II had many vascular
      channels but RPE cells surrounded the CNM. Type III showed few vascular channels
      and RPE cell proliferation. Type IV showed abundant fibrous tissue. The IA
      findings of CNM were thought to be determined by the number of vascular channels,
      maturity of vessels, degree of surrounding by RPE cells, and the amount of
      fibrous tissue within the CNM.

PMID- 9256621
TI  - [Mode of progression of visual field defects and risk factors in glaucoma
      patients].
AB  - A study of glaucoma was conducted at 17 institutions to clarify the mode of
      progression of visual field defects in specific types of glaucoma, including
      primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and
      normal tension glaucoma (NTG). Staging of glaucoma was done by the Kosaki
      Classification or the Aulhorn Classification and the mode of progression was
      assessed by life-stable method. The progressive and non-progressive groups of
      patients in each glaucoma stage were compared with respect to age, intraocular
      pressure, refraction, and optic disc cupping. A total of 656 eyes were
      investigated in 656 patients (301 men and 355 women) with a mean age of 58.0
      years. The average follow-up period was 5.8 years for the study using the Kosaki
      Classification and 4.0 years for that done with the Aulhorn Classification. The
      progression of visual field defects was rapid in the early stage but slow in the
      middle and late stages in the study by the Kosaki Classification, and it was slow
      in the late stages in the study by the Aulhorn Classification. The time for
      progression from stage Ia to stage VI was 43.3 years in the study by the Kosaki
      Classification and the time for progression from stage 0 to stage 6 was 47.2
      years in the study by the Aulhorn Classification. The progressive and non
      progressive groups differed significantly with respect to intraocular pressure at
      various stages.

PMID- 9256622
TI  - [Parapapillary chorioretinal atrophy and parapapillary avascular area in
      glaucoma].
AB  - We measured the area of parapapillary chorioretinal atrophy (PPA), i.e. zone
      alpha and zone beta in fluorescein angiography, and parapapillary avascular area
      (PPAVA) in indocyanine green angiography, using scanning laser ophthalmoscope in
      a total of 66 eyes of 39 patients. There were 26 eyes of 16 patients with normal
      tension glaucoma (NTG) and 40 eyes of 23 patients with primary open angle
      glaucoma (POAG). Although there was no significant correlation between the areas
      of PPAVA, PPA, zone alpha or zone beta, and mean deviation of Humphrey field
      analysis, there was significant correlation between all areas except for zone
      alpha and the spherical equivalent. The areas of PPAVA and zone beta in the NTG
      group were significantly larger than those in the POAG group (p = 0.04434,
      0.02750, respectively). These results suggest that the pathogenesis of disease
      may be different in NTG and POAG.

PMID- 9256623
TI  - [Effect of topically applied isopropyl unoprostone on microcirculation in the
      human ocular fundus evaluated with a laser speckle microcirculation analyser].
AB  - The effect of topically applied 0.12% isopropyl unoprostone (unoprostone,
      Rescula) on the circulation of optic nerve head (ONH) and choroid-retina was
      studied using a laser speckle tissue circulation analyser in 9 normal human eyes.
      Normalized blur (NB), a quantitative index of blood flow velocity, was measured
      every 0.125 sec and averaged over 5 pulses in the temporal site of ONH free of
      surface vessels and in the middle site of the choroid-retina between ONH and
      macula. Intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were
      also measured. On the first day, NB, IOP, BP, and PR were measured before and
      every 90 minutes for 6 hours after a 30 microliters instillation of placebo in
      both eyes (control eyes). The measured values were used as controls. On the other
      day one week later, a 30 microliters instillation of unoprostone was performed in
      one randomly chosen eye and the placebo in the other eye (treated and untreated
      eye). The above parameters were measured as the first day in a double masked
      manner. In the control experiment, no significant change occurred in any
      parameter. After topical application of unoprostone, NB in ONH showed no
      significant change. NB in the choroid-retina significantly increased at 3 (8%)
      and 4.5 (11%) hours in the treated eyes compared with the control eyes. After
      topical application of unoprostone, the IOP significantly decreased at 1.5 and
      4.5 hours in the treated eyes compared with the control eyes. BP and PR showed no
      significant change. These results suggest that instillation of unoprostone can
      increase blood flow in the choroidretna in human eyes.

PMID- 9256625
TI  - [A case of retinochoroidal optic neuropathy].
AB  - The patient was a 59-year-old male with impaired left vision. Before he was
      referred to this hospital, he was diagnosed as having optic nerve injury due to
      the trauma of a severe bruise on his left eye caused by a traffic accident, and
      relative afferent pupillary defect (RAPD) was negative. On his first examination
      in this department, RAPD was negative and funduscopy of the left eye demonstrated
      hyperemia of the optic disc and mild opacification at the posterior pole.
      Fluorescein fundus angiography showed circular hyperfluorescence around the optic
      disc and transverse linear hyperfluorescence appearing above and below the
      macula. From these findings a diagnosis of choloidal rupture was made. The form
      of choloidal rupture suggested an early stage of evulsion of the optic nerve. The
      impairment of visual acuity seemed to be caused by choloidal circulatory
      disturbance. The patient was therefore, had traumatic retinocholoidal optic
      neuropathy complicated by the rupture of the choloidal around the optic disc,
      disturbance of the optic disc, and opacification of the retinochoroid.

PMID- 9256624
TI  - [Glycohistochemical analysis of apoptotic bodies in eyelid tumor].
AB  - To clarify the relation between the mechanism of apoptosis in tumor tissues and
      sialic acids on the termini of sugar chains of glycoconjugates, a case of
      squamous cell carcinoma was examined using immunohistochemistry and
      glycohistochemistry. Immunohistochemistry and in situ hybridization
      histochemistry suggested that sialylation by the sialyltransferase in dominant in
      tumor cells, whereas hydrolysis of sialic acids by the sialidase is dominant in
      apoptotic bodies. Lectin histochemistry revealed that sialic acid alpha 2, 3
      galactose beta 1, 3 N-acetylgalactosamine (Gal beta 1, 3 GalNAc) is present on
      the surfaces of tumor cells, and Gal beta 1, 3 GalNAc is present on those of
      apoptotic bodies. The exposed Gal beta 1, 3 GalNAc owing to the decrease in
      sialic acids on the surfaces of apoptotic bodies may be recognized by the C-type
      lectin on the macrophage for phagocytosis.

PMID- 9256626
TI  - [A case of conjunctival mucosal neuroma without multiple endocrine neoplasia].
AB  - Non-traumatic conjunctival mucosal neuroma (CMN) is usually complicated by
      multiple endocrine neoplasia (MEN). We report the first case of CMN without MEN
      type IIb (III). A 14-year-old Japanese girl had CMN in the conjunctival fornix of
      right eye. CMN was diagnosed from histopathology and immunohistochemistry. T1
      weighted magnetic resonance imaging (MRI) showed a circular scribed iso-intensity
      signal, and the T2-weighted image showed iso-or high-intensity signal. There were
      no abnormal findings in the tongue, the neck or the abdomen.

PMID- 9256627
TI  - [Urgent coronary artery bypass surgery by only arterial graft for acute
      myocardial infarction].
AB  - The authors conducted urgent coronary artery bypass grafting (CABG) using only
      arterial graft for mild and moderate acute myocardial infarction (AMI) in 9 cases
      from January, 1995 through December, 1996. Mild and moderate AMI means free from
      cardiogenic shock by catecholamines alone or catecholamines and intra aortic
      balloon pumping (IABP). The period from the onset of AMI to admission was 2-24
      (average 8 +/- 6) hours. Coronary arteriography (CAG) was performed immediately
      following admission. CABG was done immediately after CAG. CPK-MB on admission was
      14-184 (average 67 +/- 61) IU/l. Three cases were main trunk disease over 90%
      stenosis, three cases were main trunk disease equivalent if another stenotic
      lesion over 99% were occluded, three cases would fall into cardiogenic shock if
      another stenotic lesion over 99% were occluded. Postoperative IABP was necessary
      for three cases. No case required repetition of IABP. For minimal operation time
      and to attain high graft flow, saphenous vein (SV) graft are generally used for
      emergencies. CABG was conducted here using only arterial graft (Mean anastomosis
      number was 2.3). There were 8 RITA grafts, 9 LITA grafts, and 4 RGEA grafts. Post
      operative CAG showed all the grafts to be patent, but string sign was noted for
      two LITA grafts. Prognosis was favorable in all cases. We could conduct urgent
      CABG surgery safely for mild and moderate AMI using only arterial grafts.

PMID- 9256628
TI  - [Surgical result of left ventricular free wall rupture complicating acute
      myocardial infarction].
AB  - From 1980 to 1995, we experienced 20 cases of surgical repair for left
      ventricular free wall rupture complicating acute myocardial infarction. These
      were divided into three types based on their clinical symptoms; 10 of the sudden
      blowout type, 4 of the rapid blowout type and 6 of the oozing type. In the rapid
      type, unconsciousness following the onset of the blowout rupture was restored by
      cardiopulmonary resuscitation (CPR) or pericardiocentesis. Seven out 20 cases
      (35%) survived. In the sudden blowout type, only one case treated by using the
      pericardial patch gluing technique without cardiopulmonary bypass survived. Three
      out of 4 cases (75%) of the rapid blow out type survived. Three out 6 cases (50%)
      of the oozing type survived. The causes of death were classified as table death
      for 5 cases, LOS for 1 case, and cerebral death for 3 cases of the 9 fatal cases
      of the sudden blowout type. Hemostasis was very difficult in 1 case of the rapid
      type. The 3 cases of the oozing type died respectively of LOS, cerebral death and
      pneumonia after surgery. Pericardiocentesis or subxyphoid drainage was performed
      preceding the repair of the rupture in 4 cases of the rapid blowout, and in 5
      cases of the oozing type. However, re-rupture occurred in 2 cases of the rapid
      type and in 2 cases of the oozing type. In 7 cases in whom pericardial patch
      gluing technique was applied, a procedure in use since 1990, all cases were
      safely weaned from CPB, with 4 cases out of 7 (57%) surviving. Meanwhile, in 13
      cases in which infarctectomy and myocardiography was carried out, 5 cases (38%)
      could not be weaned from CPB. Three cases (23%) survived after infarctectomy and
      myocardiography. Even some cases of blowout rupture were able to survive as long
      as blood pressure was elevated and consciousness was restored by CPR or
      pericardiocentesis as in cases of the rapid type. The pericardial patch gluing
      technique at the infarct site proved to be an effective procedure.

PMID- 9256629
TI  - [Complications of thoracoscopic surgery for spontaneous pneumothorax].
AB  - We reviewed the cases of 122 patients with primary spontaneous pneumothorax who
      underwent thoracoscopic surgery at our institution between 1992 and 1995. In 9
      cases, thoracotomy became necessary because of severe adhesions (3 cases), large
      foci (3 cases), and unrecognized foci (3 cases). Complications occurred in 17
      cases: collapse in 1 patient after removal of the thoracic drain, persistent air
      leakage (> 7 days) in 2 patients, and recurrent pneumothorax in 14 patients.
      There were no significant differences between the recurrent and non-recurrent
      cases in age, sex location of bullae, past history of pneumothorax, operating
      time, intraoperative blood loss, or duration of chest tube drainage after
      surgery. The interval between onset and consult was significantly longer in
      recurrent cases than in non-recurrent cases, and the number of patients who
      required chest tube drainage before surgery was significantly higher in recurrent
      cases. Reoperation was performed in 9 cases. Bullaes that were not detected
      during the first surgery were found in the 7 of these cases. The recurrent cases
      in our study were regarded as resulting from a lack of surgical skill that may
      improved with increasing surgical experience. The Brinkman index was
      significantly higher in recurrent cases. Smoking and air-leakage before surgery
      may be risk factors for recurrence following thoracoscopic surgery for
      spontaneous pneumothorax.

PMID- 9256630
TI  - [Study on risk factors and late results of coronary artery bypass grafting for
      acute myocardial infarction].
AB  - Study was made on the operative results, risk factors, and late results of
      coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI)
      conducted at our hospital. The subjects of the present study were 70 cases of AMI
      who underwent CABG during a period of five years from January 1991 to December
      1995. They were composed of 61 males and 9 females whose mean age was 61.9 years.
      LMT disease was observed in 13 cases and preoperative shock in 18 cases. The mean
      aortic cross-clamp time was 64 minutes with the mean extracorporeal circulation
      time being 134 minutes and the mean number of grafts being 2.5. The mean
      preoperative-postoperative peak creatine kinase was 4479 IU/L. The number of
      operative deaths was 14 with a mortality rate of 20%. When compared with elective
      cases of CABG conducted during the same period with a mortality rate of 2.7%, the
      operative result of AMI was poor. The mortality rate by risk factor was 40% for
      age of 70 years or more, 46.2% for complication of LMT disease, 52.9% for
      preoperative shock, 58.3% for preoperative C.I. of less than 2.0, 80% for
      postoperative C.I. of less than 2.0, 28.2% for conduct of postoperative
      circulatory support, and 42.1% for peak creatine kinase of 5000 IU/L or more.
      Aortic cross-clamp time and reperfusion time (interval from onset of AMI to
      aortic declamp) were found not to be risk factors. Late death accounted for 5
      cases including one case of cardiac death due to suspected AMI. Survival rate
      excluding operative deaths and hospital deaths was 98% in one year and 83.9% in
      five years. When compared to non cardiacevent cases, the survival rate of
      positive cardiac event cases was significantly poor. The operative results of
      severe myocardial ischemia cases represented by cases of complication of LMT
      disease were poor and it is considered that improvement of intraoperative
      myocardial protection and aggressive use of postoperative circulatory support are
      necessary in the future. The survival cases of those who could endure surgery was
      comparatively satisfactory, but when cardiac event developed, prognosis was poor
      and thus more rigid follow-up is considered to be necessary.

PMID- 9256631
TI  - [Sasumata(U+I) shape skin incision for the surgery through median sternotomy].
AB  - Since April, 1994 we have tried median sternotomy in a new skin incision which
      resembles to "Sasumata", a Japanese historical weapon of police, for the surgery
      of eleven patients with thymic disease or lung cancer for cosmetic reasons. An U
      shaped skin incision in the upper half portion of the breast and a vertical
      incision from the bottom of "U" to xyphoid process were made. A comparison was
      made in eight patients with former conventional method, a linear incision on the
      sternum. The new incision was useful not only for cosmetic reasons but also for
      the following reasons; enough operation area, good lymph node dissection from
      lower neck to upper mediastinum without additional collar incision, and good
      healing of the skin. There were no differences between the two incision groups on
      operation time, bleeding volume and hospital stay after surgery. In a
      postoperative research almost all patients have been satisfied with the new
      incision.

PMID- 9256632
TI  - [PCR-RFLP analysis of epithelium in canine cryopreserved tracheal allograft].
AB  - In this study, we investigated whether the regenerated epithelia were recipient
      phenotype or donor phenotype using PCR-RFLP (polymerase chain reaction
      restriction fragment length polymorphism) method. Preoperatively 24 mongrel dogs
      were classified to 14 types by PCR-RFLP result from peripheral blood. The PCR
      RFLP result of peripheral blood agreed to that of recipient epithelia. The
      cryopreserved tracheal allotransplantation was performed among the five pairs in
      which we could distinguish donor from recipient by PCR-RFLP. The epithelia of
      graft at 10 days after transplantation showed donor phenotype, but the epithelia
      at postoperative 20 days or more showed recipient phenotype. These results showed
      that allogenic epithelium remained in early post-transplant time and was
      gradually omitted. The epithelia migrated gradually from the anastomotic site,
      and the graft was covered with regenerated epithelia showing recipient phenotype
      within about 50 post-transplant days.

PMID- 9256633
TI  - [Cerebral cytochrome oxidase monitoring by near infrared spectroscopy during
      selective cerebral perfusion].
AB  - To evaluate selective cerebral perfusion (SCP) for brain protection, the redox
      state of cytochrome oxidase (Cyt. aa3) in brain tissue were studied in 27
      patients with thoracic aortic repair. The redox state of Cyt. aa3 was monitored
      by near infrared spectroscopy (NIRS) (OM-110, Shimazu). There were no significant
      changes in the Cyt. aa3 redox state in 13 (Group I), the oxidation state of Cyt.
      aa3 decreased then recovered to control levels in 12 (Group II), and the
      oxidation state decreased but did not recover in 2 patients (Group III).
      Postoperative cerebral damage was observed in 5 patients; blindness occurred in
      one patient in Group I (8.3%), 2 patients developed hemiplegia in Group II
      (15.4%), and the 2 patients in Group III failed to reawaken (100%). The incidence
      of cerebral damage was significantly higher in Group III than in Groups I and II
      (p < 0.05). We conclude that monitoring the redox state of Cyt. aa3 using NIRS is
      useful in predicting postoperative cerebral damage. However, it is necessary to
      increase the number of measurement sites since NIRS can reflect the state in only
      a small area of the brain.

PMID- 9256634
TI  - [Experimental study on the effect of simple percutaneous left heart bypass (LHB)
      in cases of brain death--hemodynamic and histological evaluation].
AB  - Preservation of the donor heart is an important and controversial subject in
      heart transplantation. The donor's heart function must be maintained at the most
      viable state possible. This study examined the effectiveness of LHB in cases of
      brain death and clarified the possibility of this application for donors as a
      bridge to heart transplantation. Changes in hemodynamic parameters and
      histological findings in brain-dead dogs were studied. Two groups of brain-dead
      dogs were involved in this study: group L (n = 10) as a LHB support and group C
      (n = 10) as a control. Brain death was induced by an ethanol injection into the
      subdural space of the dogs. This condition was maintained with volume replacement
      and dobutamine administration (5 micrograms/kg/ min). In group L, LHB that was
      achieved with a transaortic valve left ventricular drainage cannula inserted from
      a carotid artery and return via a femoral artery cannula was performed after
      brain death. A Bio-pump was utilized for the kind of assist device. Left
      ventricular output assist ratio averaged 60%. The parameters of left ventricular
      function (Max. dp/dt, Emax) at the time of brain death deteriorated by about 70%.
      In group L, they could keep this level over the 6-hr study period. On the other
      hand, the Emax value at 3 hours and the Max. dp/dt value at 4 hours decreased
      significantly when compared to the time of brain death (0-hr) for group C. At the
      6-hr study period, histological findings showed only minimal change in the
      myocardium with slightly interstitial edema in group L. On the other hand, severe
      ischemic change in the myocardium with many contraction bands was found in group
      C. This data suggests that LHB is effective to preserve heart function in cases
      of brain death. This application may make it possible to maintain the viability
      of other organs by maintaining circulatory blood flow and pressure.

PMID- 9256635
TI  - [A successful mitral valve replacement for a 13-year-old girl with mitral
      stenosis and pulmonary hypertension after renal transplantation].
AB  - Mitral valve replacement was successfully performed in a 13-year-old girl due to
      severely calcified mitral valve stenosis and pulmonary hypertension who had
      undergone renal transplantation from her father at the age of 8 years old.
      Although, percutaneous transluminal mitral commissurotomy had been performed for
      four times until January 1996, severe mitral stenosis could be relieved and she
      was transported to our hospital in emergency for respiratory failure caused by
      pulmonary edema. Then we decided to perform mitral valve replacement. The
      operation was done successfully using trans-septal superior approach with SJMHP
      19 mmM. the blood cyclosporin levels were monitored and controlled within normal
      limits. This is the first successful case of pediatric open heart surgery after
      renal transplantation to our knowledge.

PMID- 9256636
TI  - [A case of saphenous vein graft donor site dermatitis].
AB  - A 65-year-old male, underwent coronary artery bypass grafting, was seen for a
      saphenous vein graft donor site dermatitis, at 3 weeks after the surgery. He
      complained pruritic erythema on the lesion identical to those with numbness. The
      lesion was controlled with topical steroid for 10 days. Saphenous vein graft
      donor site dermatitis has not been recognized well by surgeon in Japan and the
      etiology is still unclear.

PMID- 9256637
TI  - [A case of primary fibrous histiocytoma of the lung].
AB  - Fibrous histiocytoma is non-epithelial malignant tumor mainly arising from soft
      tissue in extremities and body. Those derived from lung are rare. A 71-year-old
      female was admitted to our hospital because of an abnormal shadow on chest X-ray
      film. Preoperative diagnosis was not obtained by various examination. The tumor
      was located in right upper lobe (S2) and partial resection of right upper lobe
      was performed. Pathological diagnosis was fibrous histiocytoma of borderline
      malignancy. After the operation, adjuvant therapy was not done. The patient is
      doing well without recurrence and metastasis, during 4 years after the operation.
      However, careful follow-up should be necessary for long term.

PMID- 9256638
TI  - [A case of successfully treated fungal tricuspid infective endocarditis with
      repeated pulmonary embolism].
AB  - A case of successfully treated fungal tricuspid infective endocarditis with
      repeated pulmonary embolism is reported. A 60-year-old man had received along
      term intravenous hyperalimentation for the treatment of the complication after
      hepatopancreatoduodenectomy, associated with Candida sepsis. He was once
      discharged, successfully treated with antifungal agents. But he was readmitted to
      our hospital due to fever, cough and chest pain. Blood culture revealed Candida
      tropicalis. Pulmonary scintigraphy and angiography revealed multiple infarcts of
      the right lung, and echocardiography showed vegetation on the tricuspid valve.
      Because of exacerbation of shortness of breath, tricuspid valvuloplasty and
      thromboembolectomy in the pulmonary arteries was performed. Postoperative course
      was uneventful and he had a marked improvement of dyspnea after operation.

PMID- 9256639
TI  - [Monitoring for spinal cord ischemia by the use of the motor evoked potentials,
      the evoked spinal cord potential and the segmental evoked spinal cord potential
      during thoracoabdominal aortic surgery--a case report].
AB  - A 55-year-old woman, who was detected an enlargement of the aorta with body CT,
      was admitted to our hospital. Preoperative examination revealed that the aneurysm
      was expanded from ascending aorta to the abdominal aorta above the celiac artery.
      She underwent total arch replacement using elephant trunk technique. Forty-four
      days after operation, she underwent thoracoabdominal aortic replacement with
      monitoring for spinal cord ischemia by the use of the motor evoked potentials
      (MEP), the evoked spinal cord potential (ESCP) and the segmental evoked spinal
      cord potential (S-ESCP). Under the partial cardiopulmonary bypass with femoral
      venous drainage and femoral arterial cannulation on normothermia, the aneurysmal
      part of the aorta was segmentally cross-clamped and the three lumbar arteries and
      the celiac artery were reconstructed one by one. During the operation, the
      monitor showed no remarkable change, even while the aorta was cross clamped. Her
      postoperative course was uneventful without any spinal cord damage. Combined use
      of MEP, ESCP, and S-ESCP was useful for monitoring spinal cord injury during
      thoracoabdominal aneurysmal repair.

PMID- 9256640
TI  - [A case report of postcoarctation mycotic aneurysm after surgical treatment for
      cerebral arterial aneurysms].
AB  - Postcoarctation mycotic aneurysm of the aorta is very rare. We present a case of
      a 55-year-old man with postcoarctation mycotic aneurysm of the aorta infected
      with methicillin resistant staphylococcus aureus (MRSA) after surgical treatment
      for cerebral arterial aneurysms. The operation was performed after negative
      conversion of MRSA in blood culture using antibiotics. The mycotic false aneurysm
      was completely resected following institution of an extra-anatomical bypass from
      the ascending aorta to abdominal aorta above celiac artery.

PMID- 9256641
TI  - [A case of intrathoracic chondrosarcoma of the rib head--comparison between MRI
      shadow and histopathological specimen].
AB  - A 71-year-old man was admitted our hospital because of mediastinal tumor. On
      chest X-ray, the mass was about 10 cm in diameter, contact with the right side of
      No. 3-5 vertebra and extended to the right thorax. After about 8 months, he felt
      anterior chest and back pain. Tumor was growing on chest X-ray and, on chest CT,
      linear and spotty calcification existed in it. On MRI, T1 weighted image, most
      part of tumor was low signal area but high area was also existed and it was
      parenchymatous hemorrhage. On T2 weighted image, tumor was high signal and
      irregular low area was calcification. Operation was performed and a hard tumor,
      measured 12 x 9 x 6 cm, originated from the 3rd-4th rib was resected.
      Histopathological diagnosis was chondrosarcoma. MRI was effective for the
      diagnosis of this case.

PMID- 9256642
TI  - [A successful retraining of the left ventricle with a left ventricular assist
      device (bio-medicus) after the arterial switch operation].
AB  - We experienced the case of a patient with d-TGA, small VSD who underwent arterial
      switch operation (ASO) at the age of 8 weeks. In pre-operative UCG, the LV
      posterior wall thickness was only 3.0 mm. LV systolic pressure had dropped to 29
      mmHg at the time of operation. After arterial switch and VSD closure, myocardial
      contractility and coronary perfusion were good without any ST-T changes, however,
      the patient could not be weaned from cardiopulmonary bypass. Left ventricular
      assist device (LVAD) was then applied and LV training was performed with
      appropriate pre and after-load. On the 4th operative day, the patient was
      successfully weaned from LVAD. Training of the left ventricle with LVAD will be a
      useful life-saving method in the case of left ventricular failure after arterial
      switch operation.

PMID- 9256643
TI  - [Hemobilia after percutaneous transhepatic gallbladder drainage for cholecystitis
      in a patient undergoing aortic valve replacement].
AB  - A 50-year-old man with hemobilia after percutaneous transhepatic gallbladder
      drainage (PTGBD) for cholecystitis is presented. PTGBD had been performed for
      acute cholecystitis following aortic valve replacement. A combination of aspirin
      and warfarin as anticoagulant therapy had been administrated with the prothrombin
      time of approximate 40%. Six months later, the patient was again admitted to our
      hospital because of jaundice, high fever and digestive bleeding. PTGBD was again
      attempted under the diagnosis of acute cholecystitis. Endoscopic retrograde
      cholangiopancreatography revealed coagula which were excreted from the papilla of
      Vater, thus followed by a cholecystectomy accompanying with a choledochotomy.
      Three ulcers were observed in the cut surface of the resected gallbladder.
      Microscopic examinations of the gallbladder showed hemorrhage and inflammation.
      We reported out patient because hemobilia in the chronic phase after aortic valve
      replacement is rare.

PMID- 9256644
TI  - [Surgery for acute aortic dissection extending to the aortic root using gelatine
      resorcine-formol biological glue--a case report].
AB  - A 73-year-old woman was admitted with chest pain of sudden onset and hypotension.
      Enhanced CT showed the dilated ascending aorta with an intimal flap. Emergency
      surgery was performed under a diagnosis of type A acute aortic dissection and
      cardiac tamponade. Replacement of the ascending aorta was planned, but during the
      operation we found that the dissection had extended to the aortic root and that
      the laceration of the adventitia was located just distal to the aortic annulus.
      Since the laceration was closer to the aortic annulus than the coronary ostium,
      it was impossible to reconstruct the aortic stump by classical techniques using
      Teflon felt strips. Gelatine-Resorcine-Formol (GRF) glue was therefore used to
      reinforce the proximal aortic stump. We then curved the suture line of the
      proximal anastomosis so as to resect the laceration while preserving the ostia of
      the coronary arteries. We were thus able to perform simple replacement of the
      ascending aorta successfully and the postoperative course was uneventful. By
      using GRF glue, replacement of the aortic root can be avoided in such cases.

PMID- 9256645
TI  - [Two clinical case of spontaneous hemopneumothorax caused by aberrant vessel].
AB  - Spontaneous hemopneumothorax is a rare disease and intrathoracic bleeding
      reportedly occurs in the detached region of adhesive parietal pleura, aberrant
      vessel and cystic wall. We experienced two cases of bleeding most likely from the
      aberrant vessel. One patient was a 25-year-old male who had severe chest pain
      with dyspnea for four days. Chest X-ray revealed left pneumothorax and
      mediastinal shift to the right. Approximately 1500 ml of blood was aspirated from
      the left thoracic cavity. Since bleeding continued, emergency thoracotomy was
      performed. A restiform structure was noted in the bulla at the apex of the lung
      and the stump of the structure was considered as the source of bleeding. The
      other patient was a 29-year-old male who underwent emergency operation 16 hours
      after the massive bleeding amounting to 1800 ml. At the thoracotomy, a ruptured
      bulla at the apex of the collapsed lung with restiform structure was encountered.
      The bleeding point in the stump of the structure was ligated and the ruptured
      bulla was resected. In the histological study of these patients, an aberrant
      blood vessel was revealed in the restiform structure, which suggests the etiology
      of the bleeding. Their postoperative course was uneventful and had no symptom at
      the discharge. In the management of spontaneous hemopneumothorax, early
      thoracotomy should be the first consideration taking into account the massive
      bleeding from the aberrant vessel as in the cases.

PMID- 9256646
TI  - [Emergent mitral valve replacement in the second trimester of pregnancy].
AB  - A 28-year-old woman with heart failure was hospitalized at 21 weeks of gestation.
      Nine years previously mitral regurgitation was diagnosed, and she underwent
      mitral valve replacement with a Carpentier-Edwards pericardial valve.
      Echocardiography revealed primary tissue failure of the mitral prosthesis.
      Emergent mitral valve replacement was performed. Normothermic high-flow high
      pressure pulsatile perfusion was performed during cardiopulmonary bypass. Fetal
      heart rate was monitored, and it remained above 150 bpm throughout the operation.
      No bradycardia was observed. The degenerated prosthetic valve was replaced with
      another Carpentier-Edwards pericardial valve to ensure a safe pregnancy and
      delivery. Pregnancy was carried to term, and a healthy baby was delivered
      vaginally.

PMID- 9256647
TI  - [A case of primary pulmonary intimal sarcoma of the pulmonary artery].
AB  - We report the pulmonary intimal sarcoma of the pulmonary artery which is
      encountered infrequently. The patient, a 67-year-old man, was admitted with right
      heart failure. Diagnosis was not established completely by computed tomography of
      the thorax, pulmonary angiogram and pulmonary scintigram, therefore chronic
      pulmonary thromboembolism was suspected. Palliative resection was performed with
      cardiopulmonary bypass and total circulatory arrest. Pathologic examination of
      the resected tumor revealed pulmonary intimal sarcoma, which originated from the
      pulmonary artery. The patient died four months postoperatively. The cause of
      death was determined by autopsy to be recurrent pulmonary intimal sarcoma
      invading the left atrium and multiple metastasis of the brain, pancreas, adrenal
      glands and right lung.

PMID- 9256649
TI  - [A successful Konno's operation for subaortic stenosis progressed after total
      correction of partial atrioventricular septal defect associated with
      polysplenia].
AB  - Konno's operation was successfully performed on a small infant, weighing 3.8 kg.
      She underwent pulmonary artery banding on the 29th day of life under the
      diagnosis of partial atrioventricular septal defect with a small left ventricle,
      associated with polysplenia. Intracardiac repair was subsequently performed on
      the 45th day of life, which included atrial partition and mitral valvuloplasty.
      Eleven months after the second operation, wedge resection on the narrow subaortic
      fibrous lesion was done concomitant with mitral revalvuloplasty. However,
      repeated echocardiac study disclosed progression of subaortic stenosis. Cardiac
      catheterization performed at 2 years of age showed the pressure gradinet of 90
      mmHg between the aorta and the LV. The aortic annulus and the subaortic lesion
      measured 10 mm and 4 mm in diameter respectively. Severe subaortic stenosis was
      created by protrusion of abnormal mitral tissue to the LV outflow, in addition by
      secondary circumferential fibrous tissue growth and hypertrophy of the
      ventricular septum. Konno's operation using on 18A Carbomedics valve was chosen
      for the certain relief of the subaortic stenosis. Although the operation required
      extensive ventriculotomy and septostomy because of the small aortic annulus, the
      postoperative course was uneventful. Two months after the operation
      echocardiography showed good LV function and low RV pressure of about 40 mmHg.

PMID- 9256648
TI  - [Esophago-bronchial fistula which developed after the insertion of an expandable
      metallic stent for corrosive esophageal stenosis].
AB  - A 69-year-old man attempted suicide by abdominal penetrating injury and taking
      sulfonyl acid. After a laparotomic drainage operation, corrosive esophageal
      stenosis occurred. Esophageal bougienage was not effective. An expandable
      metallic stent (GIANTURCO-ROCHE Z stent, Cook Bloomington U.S.A.) was inserted
      aiming to achieve temporary oral diet and nutritional improvement. But diet did
      not improve sufficiently because of the awareness of the prosthesis, severe
      hiccup, uncontrolled regurgitation esophagitis and restenosis caused by
      intraluminal mucosal growth. After 4 months of insertion, an esophago-bronchial
      fistula was produced by the wire of EMS. An operation became necessary for this
      complication. No data exist on the long-term use of the EMS and it is not
      suitable for benign esophageal stenosis. Unavoidably if the palliative treatment
      of endoprosthesis is necessary for benign esophageal stenosis such as corrosive
      esophageal stenosis, a removable esophageal tube prosthesis is preferable.

PMID- 9256650
TI  - [A case of quadricuspid aortic valve associated with aortic steno-insufficiency].
AB  - A case of quadricuspid aortic valve associated with aortic steno-insufficiency
      was described. A 60-year-old man who had been shown to be suffering from heart
      murmur was admitted to our hospital. Both aortogram and echocardiogram showed a
      significant aortic insufficiency with mild stenosis. The aortic valve revealed 4
      cusps consisting of 3 equal cusps and a smaller cusp and it had a poor coaptation
      and mild calcification at each commissure. The coronary orifices were normally
      located. Aortic valve replacement was carried out with a 25 mm St. Jude Medical
      valve. Histological findings showed edematous and fibrous changes. His
      postoperative clinical course was uneventful. Quadricuspid aortic valve is rare
      and the literatures were reviewed with 33 reported cases in Japan.

PMID- 9256651
TI  - [NO inhalation therapy for post-operative pulmonary hypertensive crisis of the
      case of truncus arteriosus].
AB  - Two-months-old baby underwent complete correction by Barbero-Marcial's procedure
      for type I truncus arteriosus. Postoperative hemo-dynamics was fairly stable
      immediately after the operation. However, the acute rise in pulmonary pressure
      occurred on the 2nd postoperative day. The pulmonary vasodilation therapy with
      prostaglandin E1 and amrinone had failed. Thirty ppm of inhaled nitric oxide (NO)
      was started and it resulted in an immediate decrease in pulmonary arterial
      pressure. Complete weaning from NO was achieved 9 days after surgery by
      simultaneous administration of PGE1 and amrinone. Although inhalation of NO
      reduced pulmonary arterial pressure, combination of PGE1 and amrinone with NO
      inhalation exerted a pulmonary vasodilation and brought the patient to full
      recovery in this case with pulmonary hypertensive crisis.

PMID- 9256653
TI  - Maori cultural identity and the New Zealand search for nationhood.
AB  - Maori cultural identity has been seriously eroded by military might, the law,
      loss of land, exclusion from power, and economic deprivation. The effects remain
      evident and are related to a variety of sociocultural problems. This paper
      focuses on conditions which undermined a positive Maori identity and discusses
      measures likely to lead to a restored sense of positive identity including
      opportunities to reinforce cultural identity in mental health services. If people
      are able to have access to the Maori world, and to society's institutions and
      professions without being required to relinquish their own culture, identity can
      be secured more firmly.

PMID- 9256654
TI  - An analysis of the sociopolitical context of mental health nursing practice.
AB  - This paper will explore the delivery of mental health nursing care within a neo
      liberal model of mental health care delivery in New Zealand. Mental health
      nursing as a socially constructed activity occurs within a particular political
      context, which determines its role and function. This environment determines the
      nature of the nurse-patient relationship which is integral to the role of mental
      health nurses. Critical analysis of the New Zealand Government's neo-liberal
      health policies will be conducted to explore their effect on mental health care
      delivery and the nurse-patient relationship. Some of the ideologies and values
      maintained by current dominant discourses within nursing and the State are
      discussed. To establish therapeutic partnerships with service-users, mental
      health nurses are urged to critically analyse their practice and the context in
      which it occurs.

PMID- 9256655
TI  - Engendering cultural sensitivity in nursing students.
AB  - Acknowledgement of the cultural aspects of the person is necessary if nurses are
      to provide holistic care to the recipients of health-care services. The nature of
      the content to be delivered, as well as the timing and strategies for integrating
      content into the curriculum, are well debated. A range of innovative educational
      strategies used by the School of Nursing at the Queensland University of
      Technology (QUT) to provide students undertaking the Bachelor of Nursing
      programme with greater awareness of cultural issues are presented. At QUT,
      culture is a theme that arises throughout the curriculum. Opportunities for
      applying these principles within cross-cultural clinical settings are made
      available to students. Feedback from students on a clinical placement in
      Northland, New Zealand are provided as anecdotal evidence of the effectiveness of
      these strategies.

PMID- 9256656
TI  - Reporting mental health: a discourse analysis of mental health-related news in
      two Australian newspapers.
AB  - This article reports the findings of an analysis of mental health-related news
      items in two Australian newspapers-one with a national readership, the other
      being more regionally orientated-over 1 year. The study employs both descriptive
      and interpretative methods in analyzing how messages about mental health and
      illness, mental health policy, psychiatry, mental health nursing and other mental
      health-related topics, are constructed and conveyed in the print media. Which
      stories are carried both nationally and regionally? How are these framed? Which
      points of view get canvassed? Which social and political interests are ignored or
      under-represented?

PMID- 9256657
TI  - Responses of perioperative nurses to organ procurement surgery.
AB  - For many hospitals, organ retrieval surgery has become a reality. Organ retrieval
      surgery is an emotive procedure, fraught with ethical and moral dilemmas
      (Barzizza, 1990; Kawamoto, 1992). Perioperative nurses who participate in the
      procurement phase of organ donation are subject to emotions that could be
      potentially difficult. There is a need for greater understanding of perioperative
      nurses and their responses to procurement surgery. Increased knowledge of the
      procedure of organ procurement surgery, in addition to greater emotional support
      and follow-up can only serve to improve perioperative nurses' belief in
      themselves as an important link in the process of organ donation, procurement and
      transplantation.

PMID- 9256658
TI  - The rocky road to RN first assistant.

PMID- 9256659
TI  - Blueprint for: curricula development for the role of perioperative nurse
      anesthesia (PNA) and surgery (PNS).

PMID- 9256660
TI  - Over-draping: a practice question.
AB  - Traditional OR practices are under scrutiny today and perioperative practitioners
      are being asked to examine practices which do not affect the quality of patient
      care but potentially impact the cost of delivery. This article focuses on
      overdraping related to disposable products and proposes improved liaisons between
      supply and demand.

PMID- 9256661
TI  - Significant savings achieved by implementing event related outdating.
AB  - The event related outdating(ERO) theory is based on the assumption that items
      that are properly cleaned, wrapped, sterilized, stored and handled will remain
      sterile indefinitely unless the integrity of the package becomes compromised. The
      authors describe how one Surgical Suite (performing approximately 600
      cases/month) implemented an ERO program with estimated annual savings of almost
      $10,000/year.

PMID- 9256662
TI  - Nurse first assistant: an evolving project in Quebec.
AB  - Changes in the work environment, quotas imposed on the number of resident
      physicians, scientific and technological advances, and nurses having to play two
      roles, that of scrub nurse and of nurse first assistant, have all contributed to
      the development of a new role, that of nurse first assistant. For the purpose of
      providing optimal quality care to patients and at the request of its surgeons,
      the Montreal Heart Institute has presented a project to the Ordre des infirmieres
      et infirmiers du Quebec and the Professional Corporation of Physicians of Quebec.
      The project was accepted by both bodies. The OIIQ moved in favour of recognizing
      the function of nurse first assistant in September, 1994, and the PCPQ gave its
      approval for the project on March 30, 1995. A 186 hour training program was
      developed. The two selected nurses have been trained and have been integrated
      into a medico-surgical team since February, 1996. The Nurse First Assistant pilot
      project will be evaluated in February, 1997.

PMID- 9256663
TI  - An undergraduate preceptorship in the perioperative specialty.

PMID- 9256664
TI  - The discontent of the nineties--one nurse's perspective.

PMID- 9256665
TI  - Chaos theory and the partnership concept.

PMID- 9256666
TI  - Process improvement as a constant. Interview by Marie Manthey.

PMID- 9256667
TI  - Delegation: risk management implications for nurses.

PMID- 9256668
TI  - Taking rage to the Orient.

PMID- 9256669
TI  - Religious well-being in noninstitutionalized elderly women.
AB  - Spirituality is recognized as an important component of health care practice with
      elderly people. Yet, discussion of the role it plays in elderly women on a day-to
      day basis is minimal, and it is frequently not addressed in quality-of-life
      studies in this population. The purposes of this study were to describe the level
      of religious well-being and selected characteristics of religiosity in a sample
      of 114 non-institutionalized, largely rural elderly women (Mdn age = 75), as well
      as to identify the relationship between selected factors and the level of
      religious well-being. Descriptive research revealed a high level of religious
      well-being among the participants and significant positive correlation between
      religious well-being and the variables of social support and hope (p < .001).
      Through stepwise multiple regression, hope emerged as the single significant
      predictor of religious well-being (p < .001), explaining 31% of the variance in
      the dependent variable. The majority of respondents reported regularly
      participating in religious activities, highly rated the value or influence of
      religious beliefs in their lives, and identified that religious beliefs become
      increasingly important with age. Conducting a comprehensive assessment and
      implementing focused interventions associated with religious well-being will
      strengthen the scope of health care practice for elderly women.

PMID- 9256670
TI  - How race affects health services use by older women.
AB  - In this study, we examined the relationships among functional health and its
      correlates in a sample of 101 low-income, older African American (n = 32), White
      (n = 37), and Hispanic (n = 32) women residing in the southwestern United States.
      Statistically significant associations were found among age, education, and
      income and the functional health variables of physical health, independent
      health, and psychosocial health. Hispanic women reported higher levels of
      physical health than White. African American women reported higher levels of both
      independent and psychosocial health than White women. Through regression
      analysis, physical health was found to be a significant predictor of the need for
      and use of health services. Little emphasis has been placed on the functional
      health needs of older women and race in policy and practice.

PMID- 9256671
TI  - The menopausal experience of African American women: overview and suggestions for
      research.
AB  - Menopause and its effects on women's health status and needs have only recently
      received the increased attention of scholars and clinicians that many feel is
      long overdue. However, one major area of neglect that continues today regards the
      climacteric in minority populations within the United States, including the
      largest minority group, African Americans. This review summarizes issues that
      have potentially limited the amount of information available regarding menopause
      in African Americans. These issues include differing perspectives on the
      climacteric within research and clinical arenas, the difficulty of studying race
      as a variable in scholarly investigations, and methodological factors that have
      led to underrepresentation of minorities in studies of menopause. General
      considerations, as well as specific suggestions, for research questions when
      investigating the climacteric experiences of African American women are offered.

PMID- 9256672
TI  - Using the Health Belief Model to examine and predict college women's cervical
      cancer screening beliefs and behavior.
AB  - The high prevalence of human papillomavirus (HPV) among adolescent and young
      adult women and the causal association between certain types of HPV and cervical
      cancer make regular gynecological screening and Pap smear testing essential
      health practices for young women. In this study, we used the constructs of the
      Health Belief Model (HBM) to examine the gynecological screening beliefs and
      behaviors of a sample of 400 college women. Although the constructs of the model
      were able to explain only 15% of the variance in screening behavior and 11% of
      screening intentions, the use of the HBM framework resulted in important
      information regarding the participants' beliefs.

PMID- 9256673
TI  - Women who are mothers: the experience of defining self.
AB  - Feminist poststructuralists maintain that the self develops through the process
      of social interaction and is constituted and reconstituted through the various
      discursive practices in which people participate. For mothers, Western culture
      provides a confusing blend of conflicting discourses. Whereas discourses around
      healthy self-definition stress the importance of autonomy, differentiation, and
      separation of the individual from others throughout the life cycle, discourses
      around mothering emphasize women's abnegation of the self, self-lessness, and
      self-sacrifice. Drawing on elements of phenomenological research and feminist
      inquiry, this study examined the experience of self-definition for women who are
      mothers. The study revealed three elements within mothers' process of defining
      self, including (a) nonreflective doing, (b) living in the shadows, and (c)
      reclaiming and discovering self. Within each of these elements, a number of
      themes were described and illuminated. In revealing the process of self
      definition, the women described an integral relationships between the process of
      defining self and their experience of health.

PMID- 9256674
TI  - The meaning of postponed motherhood for women in the United States and Sweden:
      aspects of feminism and radical timing strategies.
AB  - This exploratory study considered certain psychosocial, medical, and cultural
      aspects of the phenomenon of postponed motherhood for one cohort of white women
      born between 1947 and 1953 in Sweden and the United States. A cross-cultural
      comparison was made of the experience of pregnancy and the early perinatal period
      in 15 American and 16 Swedish women to find out (a) whether timing decisions
      reflected the influence of feminist ideology toward a reproductive strategy
      radically different from the conventional one, and (b) whether the pattern of
      delayed motherhood was culture specific. Results indicated that the patterns of
      delayed motherhood were culture specific. Feminist ideology clearly influenced
      the timing of the American women's first birth but was evident in Sweden. Women
      in the U.S. exhibited more nonconventional behaviors and attitudes, whereas
      Swedish women were more conventional. However, the husbands in both groups were
      remarkably similar in infant caretaking behaviors, regardless of culture and
      level of education attainment. These findings indicate postponed motherhood has
      different meanings in the cultural context of these two Western industrialized
      societies.

PMID- 9256675
TI  - "Doing the month": an exploration of postpartum practices in Chinese women.
AB  - An ethnographic approach was used to explore the cultural practices of Hong Kong
      Chinese women during the postpartum period. Seven multiparous women were
      interviewed and asked to reflect on their self-care practices within the family
      home during the month after the birth of their first child. Content analysis was
      applied to the interviews and major categories identified: good food and bad
      blood, poisonous sex, dirt and prohibitions, rest and appeasing the placenta god,
      and competing loyalties. The indication is that these Chinese mothers had
      attempted to follow their personally constructed interpretations of traditional
      customary practices, being influenced by close family members, neighbors, and
      historical precedent. These women further outlined a number of personal
      variations to traditional practices in the face of increasingly Western
      influences. We provide insights into the complexity of issues modern Hong Kong
      Chinese women face in the first postpartum month and on a more global level
      highlight the importance of culturally sensitive and congruent nursing practice.

PMID- 9256676
TI  - What's on the Internet? Services for women affected by HIV and AIDS.
AB  - In this article I report findings from a survey of Internet sites related to HIV
      and AIDS with a special focus on women. HIV and AIDS are serious threats to the
      health of women, but little has been published about the cultural, economic, and
      social environments in which these women reside, and how these environments
      relate to HIV. The Internet has become a part of many people's daily environment
      and has the potential to provide information and support for women affected by
      HIV. Findings from this study suggest that although a large number of Internet
      sites related to HIV exist, only a few are designed for women. Future research
      might investigate how Internet sites related to HIV are received by the women who
      use them, and how these sites might be improved to meet their needs.

PMID- 9256677
TI  - Saying hello again: a new approach to bereavement counseling.
AB  - It is generally accepted that the successful resolution of grief work is to say
      goodbye to the deceased. Yet many bereaved resist this therapeutic agenda,
      reluctant to relinquish the love object. By examining the aspects of the
      relationship which the bereaved is reluctant to forfeit, grief work can become an
      opportunity for the bereaved to incorporate the lost relationship into the
      present and future. The griever is encouraged to say 'hello' again to those
      aspects that were expressed in the lost relationship thus gaining greater
      personal integration and wholeness.

PMID- 9256678
TI  - The interdisciplinary bereavement team: defining and directing appropriate
      bereavement care.
AB  - Hospice bereavement care often occurs in relative isolation from other program
      components; staff and volunteers are without the guidance, consultation and
      support provided through the interdisciplinary team that is enjoyed by personnel
      working in patient care areas. This article promotes a similar interdisciplinary
      team concept that has been successfully employed in one of the country's largest
      bereavement programs. Comprised of bereavement program staff, consultants from
      the patient care program, professional and lay volunteers, this interdisciplinary
      team defines and directs interventions provided by the bereavement care program.

PMID- 9256679
TI  - Bereavement services development in a rural setting.
AB  - Functioning as a hospital-based hospice program of a large medical center,
      bereavement services are not limited to hospice families in one location.
      Bereavement services are offered to those who died within the medical center and
      to the residents of the three county area the hospice serves. This paper
      identifies ways to offer bereavement follow-up to hospice and non-hospice
      families. This will include discussion of mixing together survivors of different
      types of death in a support group atmosphere. Due to the smaller population of a
      rural setting, the need to be creative to offer bereavement services to the
      community is imperative. This paper will discuss how our Bereavement Services
      have expanded in response to the needs of the communities in the three county
      area we serve. We will discuss survey results, meeting and support group data
      used to generate supporting information to allow our services to grow. Learning
      objectives for this article consist of readers being able to identify ways to
      develop and expand bereavement services; incorporating various types of death in
      a support group setting; and ways to better serve non-hospice families in need of
      bereavement follow-up. Topics include a description of Bereavement Services; Pre
      Death Bereavement Intervention; Open and Closed Support groups; Routine
      Bereavement Follow-up of Hospice families; Quarterly Nursing Home Staff Support
      groups; Widow/Widower Brunch Social; opportunities to educate the community about
      Death/Dying; and data collection for Bereavement Needs.

PMID- 9256680
TI  - Meeting the bereavement needs of kids in patient/families--not just playing
      around.
AB  - Children grieve differently than adults. Although the unit of care in hospice is
      the patient and family, emphasis is often on the grown members of the family and
      the anticipatory grief and bereavement needs of children and adolescents are
      sometimes not met adequately. In this paper, hands-on strategies for working with
      children both before and after a significant death are presented, as well as
      appropriate context information on the grieving process for youth under age 18.

PMID- 9256681
TI  - Transcending a devastating loss: the life attitude of mothers who have
      experienced the death of their only child.
AB  - This study measured 80 mothers' attitudes about life five or more years after the
      death of their only child (mean = nine years). Participants completed the Life
      Attitude Profile-Revised. The five highest and five lowest scoring mothers were
      interviewed in depth. Discriminant analysis of participant questionnaires
      revealed that 86% of participants were correctly classified by seven variables as
      survivors (reinvestors in life) or as remaining in a state of perpetual
      bereavement. Four of these variables accounted for 39% of the variance in
      participants' life attitude scores. Interview and questionnaire findings suggest
      motherhood becomes an integral part of the self and in order to survive after the
      death of an only child it is necessary not to relinquish this construct. A
      positive life attitude was found to be an important indicator of adaptation to
      this unique form of bereavement.

PMID- 9256682
TI  - Grief and AIDS: surviving catastrophic multiple loss.
AB  - This article explores the issues of grief brought about by the AIDS epidemic. As
      people affected by the epidemic experience multiple deaths in both their personal
      and professional lives, the parallel epidemic of grief is reaching crisis
      proportions. Traditional grief responses are compared with multiple loss grief
      and appropriate clinical interventions are explored. The phenomena of trauma,
      survivor guilt, Post-Traumatic Stress Disorder and other historic examples of
      multiple loss (holocausts) are examined. The existential questions of how to hold
      hope as we live in an "abyss of trauma, death and grief" concludes this article.

PMID- 9256683
TI  - Pharmaceutical care applied to the hospice setting: a cancer pain model.

PMID- 9256684
TI  - Residents' management of the symptoms associated with terminal cancer.
AB  - The principal aim of palliative care is to bring symptomatic relief to patients
      with progressive disease. Residents graduating from a university general surgery
      training program should be competent to manage common symptoms associated with
      advanced cancer. This study used performance-based testing to evaluate the skills
      of resident physicians in managing common symptoms of a patient with advanced
      cancer. Thirty-three resident physicians (PGY 1 to 6) were presented with four
      clinical symptoms of a patient with advanced cancer: (1) nausea and vomiting
      associated with regular morphine use; (2) lack of appetite in the last weeks of
      life of a terminally ill patient; (3) constipation associated with codeine
      analgesia; and (4) dyspnea associated with diffuse lung metastases. The
      management plan for the symptom problems was evaluated by using a predefined
      checklist. A significant number of residents showed deficits in the management of
      common symptoms of advanced cancer. Scheduled dosing of antiemetics was
      infrequently prescribed for opioid-related nausea and vomiting. Most physicians
      inappropriately managed lack of appetite by using forced feeding. Opioids were
      infrequently used in the management of terminal dyspnea. The absence of
      difference in scores between junior and senior residents suggests that adequate
      management of the symptoms of terminal cancer is not being effectively taught in
      postgraduate training programs.

PMID- 9256685
TI  - Enlisting the unconscious as an ally in grief therapy: the creative use of
      affirmations, metaphors, and guided visualization.
AB  - This article explores the effective use of the unconscious as an ally in
      providing therapy to bereaved clients. The power of the unconscious, often an
      underutilized but potent resource, can be employed through the use of specialized
      communication techniques which incorporate the specific language of the
      unconscious. The following presents the therapeutic use of "embedded
      affirmations," metaphors, and guided visualizations, focused on harnessing the
      healing potential of the unconscious. Included is a step-by-step model for
      constructing a guided visualization which can be customized to meet the needs of
      both individual clients and groups.

PMID- 9256686
TI  - Parenting classes as a part of a hospice bereavement program.
AB  - The impact of a loss is felt throughout the family system with the parent-child
      relationship being particularly vulnerable. The experience of The Mount Carmel
      Hospice Evergreen Center with a parenting program is presented. Responding to the
      expressed concerns of grieving parents, a time-limited parenting group was held.
      The quantitative and qualitative results of that experience are presented. In
      addition to normalizing the experience of parenting grieving children, the group
      provided the opportunity for parents to enhance skills and learn about the need
      to respect the individuality and uniqueness of the grief work of the child.

PMID- 9256687
TI  - Differential utilization of hospice services in nursing homes.
AB  - During the completion of an interpretive evaluation project, differences in rates
      of dying patients using hospice services between nursing homes were examined.
      Rates were found to vary from 2% to 39% in 23 nursing homes owned by one company.
      Twenty of the 23 administrators responded to a survey regarding attitudes toward
      hospice care in the nursing home. Nursing homes with administrators most
      sympathetic to hospice care had rates three times higher than nursing homes with
      administrators least sympathetic. Specific concerns were discussed in interviews
      with four of the least sympathetic administrators. The findings are congruent
      with program implementation theory which describes the discretionary power of
      local administrators to limit access to new programs that they find problematic.

PMID- 9256688
TI  - Special care hospice units in nursing homes.
AB  - The emergence of hospice care in the nursing home is a trend about which we have
      virtually no information. As a first step to a more comprehensive examination of
      this phenomenon, we provide a descriptive analysis of nursing homes that contain
      special care hospice units and a preliminary analysis of the determinants of
      nursing homes with special care hospice units. We found that being small, being a
      proprietary facility, being part of a chain, and being located in a more
      competitive environment are significantly related to having a hospice special
      care unit.

PMID- 9256690
TI  - The lived experience of aloneness for older women currently being treated for
      depression.
AB  - A phenomenological study was conducted to answer the following question: What is
      the lived experience of aloneness for older women currently being treated for
      depression? Eight women from Northern Ohio composed the purposively selected
      sample. Transcriptions of each 1-hr interview were reviewed by use of Colaizzi's
      (1978) method of data analysis. The analysis identified two major experiences of
      self for all participants: aloneness in depression and aloneness in recovery.
      Five paired, and somewhat dichotomous, themes defined the essence of aloneness:
      (a) vulnerability versus self-reliance, (b) fear versus hope, (c) helplessness
      versus resourcefulness, (d) loss of self-control versus self-determination, and
      (e) identity confusion versus self-reflection. All the participants expressed
      profound feelings of moving between the five paired themes as they gained clarity
      of insight into their experiences of depression and recovery. Results of this
      study make a valuable contribution by providing important insights into the lived
      experience of aloneness among older women currently being treated for depression,
      offer direction in the assessment and treatment of these women, and serve as an
      impetus for further research.

PMID- 9256689
TI  - The caregiving story: how the narrative approach informs caregiving burden.
AB  - The burdens of giving care to a chronically ill or dependent family member can be
      overwhelming. The therapeutic utilization of narrative can assist elderly female
      caregivers to transform their feelings of depression and burden into a healthy
      acceptance of the required care and disabilities of the elder for whom they care.
      This technique, which assists clients to restory negative aspects of their
      perceived reality, has emerged from the theoretical framework of postmodernism.
      Using the narrative approach to a family case study involving a daughter and
      dependent mother, this article examines interventions that can facilitate the
      positive development of a client's caregiving story.

PMID- 9256691
TI  - Comparison of registered nurses' and nursing assistants' choices of intervention
      for aggressive behaviors.
AB  - This article extends the work conducted by Fagan-Pryor, Femea, and Haber (1994),
      in which factor analyses were used to examine the congruence between aggressive
      behavior and type of intervention warranted (verbal, chemical, or physical), as
      rated by nursing personnel. The purpose of this study was to determine if 88
      registered nurses (RNs) and 84 nursing assistants (NAs) would choose similar
      interventions for 84 aggressive behaviors. The three scales used (labeled
      Precursor, Defensive, and Acting Out) obtained Cronbach alpha internal
      consistency reliabilities ranging from .79 to .96. Analyses of variance indicated
      that RNs and NAs agreed on a set of precursor behaviors for which they would use
      therapeutic verbal intervention. RN and NA responses differed significantly only
      in prescribing the use of physical intervention for behaviors on the Defensive
      and Acting Out scales. In both situations, RNs selected fewer behaviors that
      required physical intervention than did NAs. Implications for clinical practice
      are presented.

PMID- 9256692
TI  - Risk factors, attendance, and abstinence patterns of low-income women in
      perinatal addiction treatment: lessons from a 5-year program.
AB  - The purpose of this article is to describe the risk factors, attendance, and
      abstinence patterns of 40 women who attended a model outpatient perinatal
      addiction treatment program throughout the 5 years it was funded. Data were
      regularly collected through use of semistructured interviews, randomly scheduled
      urine toxicology tests, document reviews, and self-reports, in a descriptive
      field study design. Mean age of the women was 29 years. They remained in the
      program an average of 7.89 months. A majority had two or more children, most
      (90%) were single parents, and 70% were currently in an abusive relationship.
      Abstinence was positively associated with length of time in the program (r =
      .4208; p < .01). Attendance was also positively correlated with length of stay (r
      = .6723; p < .001) as well as abstinence (r = .4454; p < .01). Results suggest
      that program attendance can be a powerful influence on abstinence, even in the
      face of the environmental stressors and developmental risk factors that place
      each woman at increased risk of relapse.

PMID- 9256693
TI  - Therapy with male survivors of sexual abuse: the client perspective.
AB  - Nineteen men who were sexually abused as children were asked what advice they
      would give to therapists who work with male survivors. Content analysis was used
      to interpret their responses. The majority of the participants described specific
      negative experiences they had had with therapists. When discussing positive
      therapeutic experiences or when imparting advice to therapists, they described
      therapy as a journey and the therapist as a guide. The six therapist traits they
      described as most helpful included being informed about male sexual abuse issues,
      informing the client about the therapeutic process, being connected to the
      client, respecting the client's process, going the distance with the client, and
      letting the client go at the right time.

PMID- 9256694
TI  - Severely and persistently mentally ill in Hawaii: profile and implications.
AB  - This study examines the characteristics, treatment, and care of severely and
      persistently mentally ill clients at Hawaii's largest public-sector psychiatric
      facility, Hawaii State Hospital. The implications of this information are
      discussed in terms of treatment and care. As was found in previous studies, the
      88 participants included in this study were mostly male, less than 40 years of
      age, with a high school education or less, and hospitalized under a penal code.
      More remarkable variations were revealed, however, when clients were grouped
      according to ethnicity and racial origin. For example, clients from marginalized
      groups had a significantly higher likelihood of violence than clients from more
      politically, economically, and socially powerful groups in Hawaii. The findings
      of this research challenge nurses to combine social advocacy with clinical
      expertise to provide effective and complete treatment and care.

PMID- 9256695
TI  - A lactation course that is available for study by correspondence.

PMID- 9256696
TI  - The Trans-Tasman Arrangement.

PMID- 9256697
TI  - Women have the innate knowledge and wisdom to birth.

PMID- 9256698
TI  - Bubbles before birth.
AB  - When a spa bath was installed in the maternity unit of Osborne Park Hospital, a
      Quality Assurance survey was undertaken to try to identify any potential
      problems. At the same time a client satisfaction survey was conducted. The study
      highlighted many benefits to the client as an alternative method of pain
      management. At the same time no obvious problems were identified. However, due to
      lack of control of the many variables, and the absence of statistical analysis,
      no definite conclusions can be drawn from the study. Positive responses from
      clients encourage us to continue to offer the spa bath as a method of pain
      management. This is an area which begs research.

PMID- 9256699
TI  - ACM Professional Development Credit Points [PDCP].

PMID- 9256700
TI  - Have we lost the art? Assessment and physical examination.
AB  - As midwives we have developed excellent skills in abdominal palpation. However
      assessment and physical examination of the woman and her family requires more
      than this. We need to develop a full repertoire of assessment skills that we can
      use, as midwives, to work in collaboration and partnership with women to provide
      the best care possible within the bounds of our practice settings. It is time to
      reflect on our competence in this area of practice and decide whether we have
      "art" in the heart of our midwifery practice.

PMID- 9256701
TI  - Fetal welfare: midwives' perspectives in Australia.

PMID- 9256702
TI  - Zimbabwe "my whay".
AB  - The following essay explores the impressions, experience and observations of an
      Australian Midwifery Tutor who has just completed over 2 years working with
      qualified midwives, student midwives and traditional midwives in remote rural
      Zimbabwe. It outlines the different approaches to hospital and clinic birth in
      Zimbabwe. How Sbona women deal with pain in labour, the effects of HIV/AID on the
      rural community and the customs associated with traditional birth.

PMID- 9256704
TI  - Forty-Ninth World Health Assembly Geneva 20-25 May 1996.

PMID- 9256703
TI  - Midwives, breastfeeding, and Baby Friendly Australia.
AB  - Breastfeeding is a fundamental practice area for all midwives in Australia, and
      most midwives and maternity units claim that they recommend breastfeeding.
      Midwives have the opportunity to support women, or to erect barriers to the early
      establishment of breastfeeding. The author contends that through an understanding
      of the Baby Friendly Hospital Initiative's "Ten steps to successful
      breastfeeding", within the social/holistic model of midwifery care, long term
      health and social benefits will ensue.

PMID- 9256705
TI  - A new protocol to co-ordinate a multidisciplinary team.

PMID- 9256706
TI  - Psychological factors in treating pressure sores.

PMID- 9256707
TI  - The effect of wound dressings on diagnostic ultrasound imaging.
AB  - A study was carried out to determine the effect of wound and fixation dressings
      on diagnostic ultrasound imaging. Each dressing was scanned with four ultrasound
      probes at two focal depth settings and the results were independently rated by
      five observers on a scale of 0-5. Data were analysed using the Chi-squared test
      and Pearson's correlation coefficient for inter-observer rating. The effect of
      the dressings was found to be independent of focal depth. Three probes produced
      similar results while the C7-4 curved array probe produced images affected by the
      dressings to a significantly greater extent. The total score for each dressing
      allows ranking according to lucency and demonstrates that hydrogel, thin film,
      and tulle gras dressings have the smallest effect on diagnostic ultrasound
      images, whereas dressings which are dense or contain air allow poor ultrasound
      penetration. It is suggested that, where diagnostic ultrasound is likely to be
      required in patients with wounds, traditional gauze-and-tape dressings should be
      avoided wherever possible as modern alternatives are available which meet the
      requirements of the wound while allowing the ultrasound system to produce a
      useful image.

PMID- 9256708
TI  - 'Mouseyes': an aid to wound measurement using a computer.
AB  - The aim of this study was to assess the efficacy of an image-area and perimeter
      length measurement system consisting of a personal computer with integral mouse
      device and a computer program, 'Mouseyes', written for the purpose. The study was
      designed to see how image area, perimeter length and curvature affected the
      overall accuracy and reproducibility of measurement. Five volunteers (three male,
      four right-handed, one left-handed) were recruited to carry out the task of
      digitising a series of 12 shapes of known dimensions. The difference between
      derived and true image measurements were investigated. The accuracy and
      reproducibility of area measurement increased with increasing area magnitude.
      Digitised areas were typically calculated with an error of 1.3% or less. The
      coefficient of variation was less than 2%, indicating a high reproducibility of
      measurement; the greatest inaccuracies and variability occurred with smaller
      sizes. The system has been proved to be a reliable, accurate and reproducible
      method for the measurement of irregularly shaped areas and linear dimensions.

PMID- 9256709
TI  - Peripheral arterial disease. 2: Anatomical investigations.
AB  - The second article in a two-part Update on the diagnosis of arterial disease.

PMID- 9256710
TI  - Pressure area care and estimating the cost of pressure sores.

PMID- 9256711
TI  - Clinical investigation of medical devices.

PMID- 9256712
TI  - Should iodine be reconsidered in wound management? European Tissue Repair
      Society.

PMID- 9256713
TI  - A team approach to wound care in pyoderma gangrenosum.

PMID- 9256714
TI  - GM-CSF in the treatment of skin ulceration in breast cancer.

PMID- 9256715
TI  - Cadexomer iodine in ulcers colonised by Pseudomonas aeruginosa.
AB  - The clinical and bacteriological efficacy of topical cadexomer iodine on venous
      leg ulcers colonised with Pseudomonas aeruginosa was evaluated in an open,
      uncontrolled, multicentre pilot study. Nineteen patients with venous leg ulcers
      (median ulcer area 15.5 cm2) were treated with cadexomer iodine paste and short
      stretch bandaging for 12 weeks or until the ulcer was healed within that period.
      Bacteriological cultures for growth of Pseudomonas aeruginosa and ulcer area
      measurements were regularly performed during the study period. Seven patients
      were withdrawn during the study period for the following reasons: pain in the
      ulcer (n = 2), ulcer enlargement (n = 2), treatment of cellulitis in non-study
      ulcer with a systemic antibiotic that is effective against Pseudomonas aeruginosa
      (n = 1), increased thyroid-stimulating hormone level (n = 1) and poor compliance
      (n = 1). In addition, one patient was erroneously withdrawn. After one week's
      treatment, 11 out of 17 patients (65%) had a negative culture of Pseudomonas
      aeruginosa. At 12 weeks, six out of eight patients (75%) had a negative culture
      and complete healing was achieved in three patients (16%). The median ulcer area
      reduction obtained at 12 weeks was 32.9%. The results indicate that cadexomer
      iodine paste might be the treatment of choice for venous leg ulcers colonised
      with Pseudomonas aeruginosa. However, a larger controlled clinical study is
      needed for final evaluation.

PMID- 9256716
TI  - Allergies in leg ulcer patients.

PMID- 9256717
TI  - The proliferation and movement of cells during re-epithelialisation.

PMID- 9256718
TI  - A guide to wound debridement.

PMID- 9256719
TI  - Chronic ulceration of the leg.

PMID- 9256720
TI  - Ageing and wounds. Part 1: Foetal and postnatal healing.
AB  - The first in a two-part series of reviews outlines the physiology of wound
      healing in the normal adult and discusses how it differs from that of the foetus.

PMID- 9256721
TI  - Community nurse education in leg ulcer management.

PMID- 9256722
TI  - Guidelines and protocols in clinical decision-making.

PMID- 9256723
TI  - Wound management in patients with traumatic injuries.

PMID- 9256724
TI  - Management of a fungating breast wound.

PMID- 9256725
TI  - Use of a hydrocolloid in over-granulation.

PMID- 9256726
TI  - Monitoring wound healing by odour.
AB  - A pilot study using electronic aroma detection was performed over a six-month
      period to assess the aroma of chronic non-healing venous leg ulcers and the
      effect of appropriate antibiotic therapy on modification of the aroma. Deep
      infection with pathogenic organisms was found on biopsy culture in 13 out of 15
      patients. Odour analysis was performed at weekly intervals on the ulcer dressings
      using an AromaScan instrument. Data points on the aroma maps moved from their pre
      treatment presentation. Alterations in aroma data correlated well with the
      progress of the ulcers. Aroma analysis is shown to be a potential tool in
      monitoring the progress towards healing of chronic venous ulcers.

PMID- 9256728
TI  - Care of the diabetic foot.

PMID- 9256727
TI  - Pain in venous leg ulcers.
AB  - A prospective study was conducted to assess the prevalence, severity and
      diagnostic utility of pain in patients with venous leg ulcers. A semi-structured
      questionnaire was completed by 140 consecutive patients in two specialist centres
      caring for patients with leg ulcers. A high proportion (64%) of the 94 patients
      with ulcers of purely venous aetiology reported severe pain; 50% of these
      patients were taking either mild analgesia or none at all. In 10 of 72 cases, leg
      elevation made the pain worse. Venous ulcers are painful. Pain in three distinct
      locations was reported by patients-within ulcers, around ulcers and elsewhere in
      the leg. The presence of severe pain does not necessarily indicate arterial
      disease or infection. Pain is, in general, inadequately controlled in these
      patients.

PMID- 9256729
TI  - Leg ulcer management in a nurse-led, hospital-based clinic.
AB  - This paper describes the clinical outcomes from a nurse-led leg ulcer clinic over
      a period of three and a half years. Leg ulcers were assessed in a structured way
      and venous ulcers were treated with four-layer compression bandaging. The study
      involved retrospective analysis of 159 patients with 180 venous leg ulcers.
      Overall healing rates were 64.5% at 12 weeks, 84.1% at 24 weeks and 91.4% at 36
      weeks. Healing rates were not affected by a history of previous ulceration or by
      bilateral limb ulceration. However, healing rates varied with previous ulcer
      duration, ulcer size and patient mobility.

PMID- 9256731
TI  - Topical analgesics in leg ulcer patients.

PMID- 9256730
TI  - Ageing and wounds. Part 2: Healing in old age.
AB  - The second part of this review outlines the physiology of wound healing in old
      age and how it differs from normal adult healing.

PMID- 9256732
TI  - Resection and reconstruction of the chest wall.

PMID- 9256733
TI  - Knowledge base and use in the management of pressure sores.

PMID- 9256734
TI  - Pressure sore protocol.

PMID- 9256735
TI  - Pressure sore protocol.

PMID- 9256736
TI  - Three weeks in Harar.

PMID- 9256737
TI  - Introduction of the "Simple Delivery Kit" in East Hararghe Zone and the effect on
      traditional practices in Ethiopia.

PMID- 9256738
TI  - Traditional birth in Zimbabwe.
AB  - Modern medical and technically advanced ways of giving birth are available in
      Zimbabwe; it is an advancing country. However, this is not the only, nor always
      the most appropriate, approach to pregnancy and childbirth.

PMID- 9256739
TI  - Thinking of working in South Africa?

PMID- 9256740
TI  - Personal accident cover. Your questions answered.

PMID- 9256741
TI  - Continuing professional development. New jargon or a workable reality?

PMID- 9256742
TI  - The European Working Time Directive.

PMID- 9256743
TI  - Midwives will carry the can.

PMID- 9256744
TI  - How midwives, community nurses and GPs cope with stress.

PMID- 9256745
TI  - Home births. A report of the 1994 Confidential Enquiry by the National Birthday
      Trust.

PMID- 9256746
TI  - Promoting breast-feeding in Lancaster.

PMID- 9256747
TI  - "Free speech". Confidentiality is a special issue ... for pregnant midwives.

PMID- 9256748
TI  - CESDI & its relationship to midwifery practice. Confidential Enquiry into
      Stillbirths and Infant Deaths.

PMID- 9256750
TI  - Communication & motherhood.

PMID- 9256749
TI  - The end of an era.

PMID- 9256751
TI  - News from Westminster on health and maternity matters.

PMID- 9256752
TI  - Midwife-led care at the Gilchrist Maternity Unit.

PMID- 9256753
TI  - Midwives' skills changing them for the better.

PMID- 9256754
TI  - "The fourth emergency service!" The RCM: caring for midwives at local level.

PMID- 9256755
TI  - All change again! Midwifery education & government initiatives.
AB  - The success of the midwifery profession in the new millennium will depend to a
      large extent on the appropriate preparation of future midwives and the continuing
      professional development of existing practitioners. Currently, pre-registration
      midwifery education, and some recordable continuing education for qualified
      staff, is regulated by the statutory body-but will this always remain so? It is
      sometimes difficult to comprehend where the seemingly endless changes in the NHS
      will lead.

PMID- 9256756
TI  - "Free speech". Teaching midwives' skills.

PMID- 9256757
TI  - Around 40% of midwives work part-time.

PMID- 9256759
TI  - "Safe in our hands". Report of the RCM annual conference, 1997--Harrogate.

PMID- 9256758
TI  - Paying the piper--calling the tune?

PMID- 9256760
TI  - The supervision education & practice programme.

PMID- 9256761
TI  - Continuing professional development. The learning organisation.

PMID- 9256762
TI  - National clinical guidelines for the care of women with symphysis pubis
      dysfunction. Association of Chartered Physiotherapists in Women's Health.

PMID- 9256763
TI  - Opinion. A neonatal cry for research.

PMID- 9256764
TI  - A midwife ventouse practitioner.

PMID- 9256765
TI  - ALSO: the Advanced Life Support in Obstetrics course.

PMID- 9256766
TI  - Midwives' network.

PMID- 9256767
TI  - Filling a vacant post can be difficult.

PMID- 9256768
TI  - Knowledge and learning needs of clients with hypertension.

PMID- 9256769
TI  - Nurses' uniform.

PMID- 9256770
TI  - A tribute to the pioneer of nursing. Miss Florence Nightingale.

PMID- 9256771
TI  - Excellence in nursing education concepts, strategies and practices.

PMID- 9256772
TI  - Reflections on Pay Commission Report.

PMID- 9256773
TI  - ANM. Her role in 'health for all by 2000 A.D.' Auxiliary Nurse Midwife.

PMID- 9256774
TI  - Perpetual notion.

PMID- 9256775
TI  - Nursing research throughout the life span: unraveling mysteries of health and
      illness.

PMID- 9256776
TI  - Freeing the ties that bind.

PMID- 9256777
TI  - Why women should exercise.

PMID- 9256778
TI  - Fevers, shivers get wrappings.

PMID- 9256779
TI  - Environment: seeking clues to Parkinson's disease.

PMID- 9256780
TI  - No limits on appetite.

PMID- 9256782
TI  - Arista II envisions nursing's preferred future role. W.K. Kellogg Foundation
      funds multidisciplinary think tank.

PMID- 9256781
TI  - Environment: perinatal lead exposure.

PMID- 9256783
TI  - Nurse fails to follow DNR order: "wrongful living" suit.

PMID- 9256784
TI  - Can a nurse "expert" testify against a physician? Case in point: Carolan v. Hill
      553 N.W.2d 882--IA (1996).

PMID- 9256785
TI  - NY: Failure to remove surgical packing: "Foreign object" & Res Ipsa not
      applicable. NY: nurse causes i.v. pole to fall on patient: surgeon not
      vicariously liable for negligence.

PMID- 9256786
TI  - Are nurses often sued as individual defendants? Case in point: Pastchol v. St.
      Paul Fire & Marine Ins. 929 S.W.2d 713--AR (1996).

PMID- 9256787
TI  - Wrong meds given pt.--death results: civil rights suit.

PMID- 9256788
TI  - LPN repeatedly rapes patient: punitive damages sought. Case on point: Weimann v.
      Meadow Manor, Inc. 674 N.E. 2d 143-IL (1996).

PMID- 9256789
TI  - AR: auto accident en route to pt.'s home: "performing service" issue--comp.
      awarded. NM: challenge to application of AMA guides: permanent partial comp.
      benefits denied.

PMID- 9256790
TI  - Hosp. reneges on exception to "use it or lose it" vacation time policy. Case on
      point: Barrilleaux v. Franklin Foundation Hosp. 683 So. 2d 348--LA (1996).

PMID- 9256791
TI  - Were both patient & chart improperly "doctored"?

PMID- 9256792
TI  - Terminated nurse sues for breach of contract and defamation. Case on point:
      McCullough v. Visiting Nurse Serv. of So. Maine 691 A. 2d 1201--ME (1997).

PMID- 9256794
TI  - Hypodermic needle left in patient: Res Ipsa Loquitur issue. Case on point:
      Dickerson v. Fatehi 484 S.E. 2d 880--VA (1997).

PMID- 9256793
TI  - LA: Pt. denied treatment commits suicide: nursing assessments & EMTALA liability.
      KS: E.R. nurse triages pt. as non-emergent: procedure followed--no EMTALA
      liability.

PMID- 9256795
TI  - Forgotten in the ER.

PMID- 9256796
TI  - Acute care decisions--ethics in action.

PMID- 9256797
TI  - Incision care that really cuts it.

PMID- 9256798
TI  - Pharmacology in practice--antidepressants and anxiolytics.

PMID- 9256799
TI  - Angina: improving the outcome.

PMID- 9256800
TI  - Caring for the world--in Atlanta.

PMID- 9256802
TI  - School nursing: way more than Band-Aids.

PMID- 9256803
TI  - The brave new world of telemedicine.

PMID- 9256801
TI  - Menopause made easier.

PMID- 9256804
TI  - A new HIV test can reduce risk of occupational injuries.

PMID- 9256805
TI  - We're not cogs!

PMID- 9256806
TI  - Caring as a multidisciplinary research field.

PMID- 9256807
TI  - Recovery and quality of life one year after coronary artery bypass grafting.
AB  - In order to study recovery and quality of life after bypass surgery, both
      objective and subjective data were collected during structured interviews. A
      total of 56 patients participated in the study. Data were collected during
      hospital admission and during two home visits at 6 and 12 months after Coronary
      Artery Bypass Grafting (CABG). Patients reported improved state of health and
      quality of life. Most of the changes occurred within the first six months after
      discharge. However, for most patients life had more or less returned to normal
      one year after CABG. It was also found that few of the patients changed their
      risk behaviour after surgery.

PMID- 9256808
TI  - Elderly people's daily activities and need for mobility support.
AB  - The aim of the present study is to describe elderly people's performance of some
      daily activities in relation to their need for mobility support in their living
      environment. Two groups of individuals, over the age of 65 and living in an old
      urban area with access to elevators in their housing, were compared, as regards
      mobility, shopping, hobbies and social contacts. The first group (n = 284)
      comprised persons who needed assistance from another person in using the
      elevator. The subjects in the second group (n = 325) were able to manage the
      elevator independently. The subjects in the first group experienced more problems
      in carrying out the activities than those in the second group. Weekly shopping
      was the only action in which the findings demonstrated no main differences
      between the groups. Throughout all the activities of daily living (ADL), and in
      both groups, there were persons who were rated as having the capacity to perform
      the activities, but did not do so and did not want to do so. The elderly,
      especially in the first group, wanted to engage in more activities than they were
      judged to have the capacity for and/or the environmental support to do. The
      implications of the result for the assessment of the homes of the elderly in
      relation to their environment are discussed.

PMID- 9256809
TI  - Health motives and life values. A study of young persons' reasons for health.
AB  - The aim of this study was to investigate the health motives of young people, i.e.
      the things that give health meaning. The investigation was carried out as two
      studies among Finland-Swedish young people aged 13-19. A questionnaire with open
      questions framed with a multidimensional perspective on health was filled in by
      152 pupils at secondary school, 121 pupils at upper secondary school and 115
      pupils at vocational school in study I. A theme interview with 15 young persons
      was the data assembling method used in study II. The data was analysed using the
      hermeneutical method. The results revealed that a young person's experience of
      health and idea of what health is cannot be understood in a deeper sense without
      understanding the young person's health motives. The health motives can be
      described at different levels as external, internal and fundamental. The
      different motives for health form health motive complexes, which are based on an
      aspiration to avoid something perceived as evil, such as illness and suffering.
      On the other hand, the motives are based on an aspiration to achieve what is
      good, such as love and life. The motives mentioned as meaningful for health have
      to do with the things that are valued in life. Consciousness of life values that
      last and can give meaning provides an answer to the 'why' of health. Humanistic
      values, existentialistic values, materialistic values or traditionalistic values
      give the clue to why health is meaningful for a young person. The results also
      indicated that there are difference in young persons' health motives in different
      school contexts.

PMID- 9256810
TI  - A philosophy of care for a neonatal intensive care unit. Operationalization of a
      nursing model.
AB  - Crisis reactions, a stressful environment, infant care practices, and nurse
      behavior may cause difficulties in entering the natural parental role for parents
      of infants who are admitted to a neonatal intensive care unit (NICU). In
      connection with discussions in the Uppsala NICU on what constitutes good care, a
      philosophy of care, based on Callista Roy's adaptation model, was formulated for
      the purpose of providing developmentally supportive, family-centered care, and
      for defining good care and the professional nurse role. The philosophy describes
      the infant's needs and environment. Caring activities focus on support of the
      infant's and his parent's roles and self-concept in their progress towards
      independence from professional assistance. The philosophy is an essential
      component in the introductory program which integrates newly recruited personnel
      from different disciplines into the unit. It is presented as a suggestion of how
      a model-based philosophy of care can be formulated by operationalization of the
      theoretical concepts of a nursing model.

PMID- 9256811
TI  - Hospital nurses' perceptions of patient teaching.
AB  - Patient teaching in general hospitals is becoming increasingly important both due
      to higher patient turnover and the principles of self-care. This study focuses on
      how hospital nurses describe ideals and realities in teaching adult patients in a
      general hospital, and how they describe the factors affecting their teaching
      function. The study has a qualitative approach. Fourteen registered nurses,
      working in a general hospital, are interviewed. The interviews are
      semistructured. The four stages adapted from Glaser & Strauss' grounded theory
      approach are used as a support in the elaboration and the analysis of the data.
      The study shows that the ideals about patient teaching are rather weakly
      articulated. The realities are, however, more distinctly described. Empirical
      findings reveal two different 'teaching processes' articulated by the informants.
      Both processes are novel and different from the traditional teaching process
      mentioned in the literature. Which processes the nurses are applying in the
      clinic seem to depend on the objective and content of the patient teaching. This
      evidence has so far not been reported in previous studies. Regarding the factors
      affecting their patient teaching, the nurses emphasize the following three; The
      nurses' qualifications, training in the teaching function and the organizational
      setting.

PMID- 9256812
TI  - Walking around in circles--the life situation of patients with asthma-like
      symptoms but negative asthma tests.
AB  - In-depth interviews were conducted with fourteen women with asthma-like symptoms
      but negative asthma tests. In collecting and analysing data the method of
      grounded theory was used. A core category emerged, Walking around in circles, and
      three main categories, Subjective Hyperreactivity, Social Limitations and Non
      Confirmation which elucidated the life situation and psychosocial processes
      involved in having the breathing disorder. The findings were characterised by
      numerous self-reinforcing vicious circles. The symptoms were especially
      associated with subjective hyperreactivity with strong sensitivity to odours,
      impaired ability to perform physical activities and mental stress, which in turn
      impose social limitations. These restrictions arouse feelings of social isolation
      and distress, which implies mental stress and thereby increased attention and
      sensitivity to adverse stimuli. The fact that the medical experts cannot offer
      diagnosis and treatment engenders feelings of confusion, non-confirmation and
      thereby anxiety which further aggravate the vicious circles described. Most
      informants considered that they had few coping strategies. Some stated that they
      had changed their strategies from being passive, taking no responsibility, to
      become more active, not caring about the reactions of others and taking the risk
      of being ill, favouring social contacts and thus minimising the impact of the
      disorder.

PMID- 9256813
TI  - Male nurses--reasons for entering and experiences of being in the profession.
AB  - In order to illuminate male nurse teachers' and nurse students' reasons for
      choosing to become nurses, and their experiences and positions within the
      profession, all 13 males among a total of 184 nurse teachers and students at one
      nursing school in Norway were interviewed twice with a 10-year interval between
      the interviews. In a personal interview in 1984 all the interviewees emphasized
      that their desire to become nurses was connected with a wish to act in a woman's
      role and expressed feminine values. The interviewees' fathers disapproved while
      their mothers approved with their choices to become nurses. The subjects thought
      that female nurses did not accept that they were bedside nurses, and exerted
      pressure on them to adopt roles within nursing that were perceived to be male;
      i.e. teachers, or administrators. In a telephone interview in 1994 they were
      asked about their experiences and positions within the profession. Eight
      interviewees had worked as nurses within psychiatric care and ten had current
      senior positions. They stated that the most positive thing in the profession was
      the contact with the patients and meaning so much to someone. All said they would
      have made the same choice today and become nurses.

PMID- 9256814
TI  - How do nurse educators respond to the challenges and changes in their working
      life in Finland?
AB  - In the present study nurse educators were asked to comment via a questionnaire on
      the characteristics deriving from earlier results and how they experience the
      present situation in their working life, and how they see the future. Data from
      65 (63% of 104) educators were analysed. The earlier results, in the form of
      statements describing the best and the worst things in nurse educators' working
      life, were generally corroborated by respondents. The best things were students,
      freedom and challenges, and the worst things were workload, inadequacy of
      personal resources and administrative issues at work. Agreement was most clear on
      the workload being the worst thing in nurse educators' working life (52 out of
      65). The explanations for agreement and disagreement were much the same as those
      given in previous studies. Regarding the present situation and the most important
      thing that needs attention in nurse educators' working life in Finland, nurse
      educators named continuous and too rapid changes. These results are related to
      workload, excessive demands and stress, competition, feelings of insecurity, and
      everlasting pressure to educate oneself. On the other hand, one's perception of
      working life is a very personal issue, and some educators who cope with it keep
      challenges as possibilities and enjoy them.

PMID- 9256815
TI  - Volunteerism and children's health insurance: expand coverage.

PMID- 9256816
TI  - The impact of policy standardization on the Medigap market.
AB  - This study examines the impact of policy standardization on the market for
      Medicare supplemental, or "Medigap," policies. Prior to 1992, insurance carriers
      could sell any benefits they chose, so long as minimum benefit requirements were
      met. In July 1992, federal legislation was implemented that required all new
      Medigap policies to conform exactly to one of 10 standardized sets of benefits.
      Using pre- and post-standardized policy information from six states, this study
      analyzes the impact of this legislation. Overall, standardization has affected
      the market positively, and as a result, consumers are better able to make
      informed choices about the benefits they are purchasing.

PMID- 9256817
TI  - Death and reputation: how consumers acted upon HCFA mortality information.
AB  - From 1986 through 1992, the Health Care Financing Administration (HCFA) released
      information comparing patient death rates at individual hospitals. This was
      viewed widely as an effort to aid consumers in selecting hospitals. This study
      evaluates how the release of this information affected hospital utilization, as
      measured by discharges. It finds a very small, but statistically significant
      effect of the HCFA data release. A hospital with an actual death rate twice that
      expected by HCFA had fewer than one less discharge per week in the first year.
      However, press reports of single, unexpected deaths were associated with an
      average 9% reduction in hospital discharges within one year. HCFA was justified
      in eliminating its mortality report, not because it was being used by consumers
      to choose hospitals, but because it was not. Implications for report cards are
      discussed.

PMID- 9256819
TI  - Defining and implementing medical necessity in Washington State and Oregon.
AB  - This paper reports on a qualitative study of how health care providers in the
      states of Washington and Oregon define and implement medical necessity. Based on
      a series of semi-structured interviews, we found that few insurers or health care
      plans in our sample attempted to resolve the ambiguities inherent in defining
      medical necessity. More importantly, our results suggest that physicians in
      managed care plans were not using general definitions of medical necessity to
      make clinical decisions, but instead relied on utilization management techniques
      to guide the use of medical resources. We conclude that medical necessity as an
      organizing principle for clinical practice decision making is likely to continue
      to erode in a managed care environment.

PMID- 9256818
TI  - Health care utilization for the "newly insured": results from the Washington
      Basic Health Plan.
AB  - The risk of providing coverage for low-income people formerly without insurance
      is unknown. We conducted an evaluation to describe the use of services from 1989
      1992 for members of the Basic Health Plan (BHP), a subsidized health insurance
      program for low-income individuals in the state of Washington. There was evidence
      of pent-up demand for care for those who had been without insurance for more than
      a year. Overall, members in the BHP program were not high users of care, although
      one of the three plans we examined had significantly higher utilization than the
      other two. BHP total expenditures were comparable to those for state employees
      and lower than those for Medicaid recipients.

PMID- 9256820
TI  - Primary care case management for Medicaid recipients: evaluation of the Maryland
      Access to Care program.
AB  - A growing number of states are implementing Medicaid managed care programs, and
      primary care case management (PCCM) is an important component of many of these
      systems. In this paper, we present results of an evaluation of one such PCCM
      program--the Maryland Access to Care (MAC) program. The evaluation uses five
      years of Medicaid claims and eligibility data from the period before and after
      the program's introduction to determine the program's impact on expenditures and
      service utilization. Results indicate that the program increased the probability
      that a Medicaid enrollee would use primary care and preventive services, but had
      little impact on use of specialty or emergency room services. The gatekeeper
      program also was successful at controlling expenditures once an enrollee entered
      the health care system, largely through reductions in the use of ancillary
      services. The post-MAC increase in the probability of using services was so
      great, however, that all savings per user were negated, resulting in an estimated
      increase of about 3.4% in Medicaid expenditures for the MAC-eligible population.

PMID- 9256821
TI  - Differences in private health insurance coverage for working male Hispanics.
AB  - In 1993, 33.8% of all nonelderly adult Hispanics living in the United States
      lacked health insurance coverage (either private or public), compared to 8.1% of
      the entire nonelderly population. Because Hispanics are more likely to be
      uninsured than any other ethnic group and because they are the fastest growing
      minority group in the United States, the increase in the Hispanic population is
      likely to increase the proportion of the population without health insurance.
      Particularly striking are differences in private health insurance coverage among
      the three major Hispanic groups--Cuban-Americans, Mexican-Americans, and Puerto
      Ricans. In this paper, regression-based decomposition analysis is used to explain
      the sources of differences in private health insurance coverage among working
      males in these three group. The results indicate that among the study population,
      Cuban-Americans have higher rates of private health insurance coverage than
      Mexican-Americans and Puerto Ricans, and that wage rates, levels of education,
      age, occupation, and marital status explain most of the difference.

PMID- 9256822
TI  - The naming of a syndrome.

PMID- 9256823
TI  - Sideroblastic anemia: a mitochondrial disorder.

PMID- 9256824
TI  - Protean manifestations of mitochondrial diseases: a minireview.
AB  - PURPOSE: Mitochondrial abnormalities are major causes of human disease. Pearson
      syndrome illustrates many features of abnormal mitochondrial function and
      genetics. DESIGN: Mitochondria from adenosine triphosphate (ATP) via five
      multienzyme complexes of the electron transport chain and oxidative
      phosphorylation, composed from a blend of nuclear and mitochondrial gene
      products. Mitochondrial DNA (mtDNA) is small (16.6 kb), encoding some subunits of
      these complexes as well as transfer RNA (tRNA) and ribosomal RNA, but is
      replicated and transcribed by nuclear encoded polymerases. Multiple copies of
      mtDNA are passed on to progeny cells via the cytoplasm, accounting for maternal
      inheritance. Normal and mutant mtDNA can coexist within the same cell
      (heteroplasmy); when the proportion of mutant mtDNA exceeds a threshold, cellular
      function is impaired, resulting in disease. RESULTS AND CONCLUSIONS: MtDNA
      abnormalities include point mutations, deletions, and depletion. Point mutations
      in an enzyme subunit cause a specific disorder, whereas point mutations in the
      tRNAs result in general impairment of protein synthesis and are associated with a
      variety of disorders. Large mtDNA deletions, initially described in Kearns-Sayre
      syndrome (KSS), were found soon thereafter in Pearson syndrome. Survivors of
      Pearson syndrome have gone on to develop KSS. A whole spectrum of disease forms,
      ranging from isolated sideroblastic anemia to combined Pearson and KSS, are
      associated with deletions of mtDNA. Diagnosis of mitochondrial disorders depends
      on clinical suspicion, enhanced by evidence of abnormal mitochondrial structure,
      number, and/or function. Effective treatment for mitochondrial disorders is very
      limited, including correction of the metabolic milieu, activation of enzyme
      activity by drugs or cofactors, and removal of reactive oxygen species.

PMID- 9256825
TI  - Arms and the man or hands and the child: congenital anomalies and hematologic
      syndromes.

PMID- 9256827
TI  - Clinical significance of the antinuclear antibody test in selected children with
      idiopathic thrombocytopenic purpura.
AB  - PURPOSE: To determine the clinical significance of the antinuclear antibody (ANA)
      test in selected children with idiopathic thrombocytopenic purpura (ITP).
      METHODS: The study was conducted through retrospective chart review and long-term
      follow-up by telephone interview. RESULTS: Of 87 children with ITP who had an ANA
      performed, 25 had a positive titer (median = 1:160, range: 1:40 to 1:2,560).
      Children with a positive ANA were more likely to be older girls who developed
      chronic ITP, but there was no correlation with family history of autoimmune
      disease, initial hemoglobin concentration, or initial platelet count. With an
      average follow-up of more than 5 years, more children with a positive ANA
      developed further autoimmune symptoms than those with a negative ANA (36% vs. 0%,
      p < 0.001). Nine children with a positive ANA developed additional autoimmune
      symptoms, including five with clinical criteria sufficient for the diagnosis of
      systemic lupus erythematosus (SLE). Autoantibodies to dsDNA were more prevalent
      in the children with progression of autoimmune symptoms (57% vs. 0%, p = 0.04).
      The presence of any autoantibody in addition to the ANA, including dsDNA, SS
      A/Ro, SS-B/La, Smith Antigen (Sm), nuclear ribonucleoprotein (nRNP), or
      cardiolipin was more common in children who had further autoimmune symptoms (75%
      vs. 0%, p = 0.003). CONCLUSIONS: The ANA is a useful screening test in a subset
      of children with ITP, especially older girls with chronic ITP, who are at risk
      for the development of generalized autoimmune disease. Children with ITP and a
      positive ANA should receive careful follow-up.

PMID- 9256826
TI  - CD44 expression in neuroblastoma and related tumors.
AB  - PURPOSE: A retrospective study was conducted to investigate the relationship
      between CD44 expression in neuroblastoma and related tumors and other known
      prognostic indicators. MATERIALS AND METHODS: Immunostaining of CD44 was done on
      surgical specimens of 55 cases (42 patients) of neuroblastoma (NB) and
      ganglioneuroblastoma (GNB) and nine cases of ganglioneuroma. The percentage of
      positive tumor cells was scored semiquantitatively (0-4+) by two observers. CD44
      expression was then correlated with survival, age, stage, and N-myc
      amplification. RESULTS: Fifty-seven percent of the patients with NB or GNB had
      heterogeneous positive staining (2-4+) on their diagnostic specimens. Twenty-four
      percent of the patients had no staining for CD44, and 19% had 1+ staining. In the
      17 cases with N-myc analysis, an inverse relationship was demonstrated between N
      myc and CD44 expression by univariate analysis. Lack of expression of CD44 was
      highly associated with poor survival (p = 0.0002). When assessing the joint
      effects of age, stage, and CD44 in multivariate analysis, the effect of CD44
      remains significant (p = 0.028) and appears to be independent of age and stage.
      CONCLUSION: Our data suggest a relationship between CD44 and N-myc amplification.
      Absence or low expression of CD44 correlates with poor survival and may be a
      biologic marker of tumor aggressiveness. CD44 appears to be an independent
      prognostic marker and deserves continued investigation in prospective studies of
      neuroblastoma.

PMID- 9256828
TI  - A phase I/II study of idarubicin (Ida) with continuous infusion fludarabine (F
      ara-A) and cytarabine (ara-C) for refractory or recurrent pediatric acute myeloid
      leukemia (AML).
AB  - PURPOSE: The goal was to conduct a phase I/II trial of escalating doses of
      Idarubicin (Ida) in conjunction with the previously established maximum tolerated
      dose (MTD) of F-ara-A/ara-C in children with refractory or recurrent acute
      myeloid leukemia (AML). PATIENTS AND METHODS: We conducted a phase I/II trial in
      parallel with Children's Cancer Group (CCG) study 0922, which involved dose
      escalation of Ida at levels of mg/m2, 9 mg/m2, and 12 mg/m2 over 15 minutes on
      days 0, 1, and 2. As phase I safety was documented by CCG, we increased the dose
      of Ida given on day 0, 1, and 2 of the F-ara-A/ara-C infusion (F-ara-A: 10.5
      mg/m2 over 15 minutes and 1.27 mg/m2/hour for 48 hours followed by ara-C: 390
      mg/m2 over 15 minutes and 101 mg/m2/hour for 72 hours). RESULTS: Ten of 15
      patients achieved remission. There was one toxic death due to adult respiratory
      distress syndrome. The median time to an absolute neutrophil count (ANC) >
      200/microliter was 29 days; ANC > 1,000/microliter was 41 days; and platelets >
      100,000/microliter was 45 days. CONCLUSIONS: A dose of 12 mg/m2/day x 3 of Ida
      did not exceed dose-limiting toxicity with this combination of F-ara-A/ara-C.
      Substantial activity of this regimen was seen in pediatric patients with AML.

PMID- 9256829
TI  - High dose cyclophosphamide with carboplatin: a tolerable regimen suitable for
      dose intensification in children with solid tumors.
AB  - PURPOSE: To determine the hematopoietic and nonhematopoietic toxicity of a novel
      dose-intensive chemotherapy regimen for the treatment of children with relapsed
      solid tumors. PATIENTS AND METHODS: The time to hematopoietic recovery and
      toxicity experienced during 46 courses of high-dose cyclophosphamide (4.0 g/m2),
      MESNA, and carboplatin (400 mg/m2) with granulocyte colony stimulating factor (G
      CSF) support in 14 children with recurrent solid tumors was reviewed. RESULTS:
      All patients developed grade 4 neutropenia and thrombocytopenia. Recovery to an
      absolute neutrophil count (ANC) of 500/microliter and platelet count of
      50,000/microliter occurred at a median of 15 days and 23 days respectively.
      Median time to ANC > 1,000/microliter and platelets > 100,000/microliter was 27
      days. Hospitalization for fever and neutropenia occurred during 35 of 46 courses,
      with documented bacteremia in six courses. There was no grade II or greater
      nonhematopoietic organ toxicity. Responses (CR + PR) were observed in 6 of 11
      evaluable patients. CONCLUSIONS: These data suggest that this regimen is
      tolerable in heavily pretreated children with solid tumors with myelosuppression
      as the primary toxicity. Due to the lack of significant nonhematopoietic
      toxicity, this is a good candidate regimen for dose escalation using peripheral
      blood progenitor cell infusions and deserves further evaluation for efficacy in
      children with both recurrent and newly diagnosed high-risk solid tumors.

PMID- 9256830
TI  - Three-year follow-up of hydroxyurea treatment in severely ill children with
      sickle cell disease. The French Study Group on Sickle Cell Disease.
AB  - PURPOSE: To observe the safety and efficacy of hydroxyurea (HU), a drug that
      stimulates fetal hemoglobin (Hb F) production, in previously severely ill
      children with sickle cell disease. PATIENTS AND METHODS: HU was given in an
      uncontrolled study to 35 children with sickle cell disease, aged from 3 to 20
      years, suffering from frequent painful crises. Mean duration of treatment was 32
      months (range: 12-59 months). RESULTS: HU induced an increase in Hb F levels in
      all children out one; this increase was maximal after 9 months of treatment, was
      largely sustained thereafter, and was related to HU dose and inversely to
      patients' age. We also noted an apparent reduction in crisis, which occurred
      principally after 3 months of therapy and did not seem strictly correlated with
      the rise in Hb F level. No serious hematopoietic complication was observed.
      Growth curves and sexual development were not modified. CONCLUSION: Our data
      support the efficacy of HU in reducing painful events in children with sickle
      cell disease. Short- and middle-term tolerances are good. Thus, we think that HU
      can be given to children affected by frequent and severe painful crises. We
      recommend, however, very cautious use of this drug, because its long-term effects
      in children are still unknown.

PMID- 9256831
TI  - Phosphotyrosyl proteins in childhood rhabdomyosarcomas: phosphorylation of
      catenins and components of the insulin-like growth factor type I receptor
      signaling cascade.
AB  - PURPOSE: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical
      presentation, histology, and cytogenetics. The growth of some RMS cells has been
      found to be regulated by the tyrosine kinase insulin-like growth factor (IGF)
      type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of
      tyrosine kinases and IGF receptors. Collectively, these heterogeneous features
      suggest that differences exist in the growth regulatory pathways of RMS. The
      objective of this study is to identify active tyrosine kinase signal transduction
      pathways in embryonal and alveolar RMS cells. METHODS: RMS tumor samples and cell
      lines representing both embryonal and alveolar histologic subtypes have been
      analyzed by immunoprecipitation and immunoblotting techniques to characterize
      phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins.
      RESULTS: RMS cells can be characterized based on the patterns of phosphotyrosyl
      proteins, including the phosphorylation status of the catenin-like protein Cas1
      and the signal adapter protein SHC, and the activation of IGF type I receptor
      signaling cascades including the formation of SHC-GRB2 signal protein complexes
      and MAP kinase activation. CONCLUSIONS: Rhabdomyosarcomas, especially the
      embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase
      signal transduction. It will be important to characterize the growth regulatory
      pathways active in individual RMS tumors before targeting molecular therapies to
      this malignancy.

PMID- 9256832
TI  - Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal
      S. pneumoniae among children with sickle cell anemia. The Ancillary
      Nasopharyngeal Culture Study of Prophylactic Penicillin Study II.
AB  - PURPOSE: To evaluate the consequences of prolonged prophylactic penicillin use on
      the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the
      prevalence of resistant pneumococcal strains in children with sickle cell anemia.
      METHODS: Nasopharyngeal specimens were obtained from children with sickle cell
      anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals
      throughout the United States. These patients were participating in a prospective,
      randomized, placebo-controlled trial in which they were prescribed prophylactic
      penicillin before their fifth birthday and were randomized to prophylactic
      penicillin or placebo after their fifth birthday (PROPS II). The specimens were
      cultured for S. pneumoniae, and isolates were analyzed for antimicrobial
      susceptibility to nine commonly prescribed antimicrobial agents. RESULTS: Of the
      226 patients observed, an average of 8.4 specimens were collected per patient.
      From 1,896 individual culture specimens, 5.5% of the specimens were positive for
      S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of
      the study patients had at least one isolate of penicillin intermediate or
      resistant pneumococci. There was no significant difference in the percent of
      positive cultures for S. pneumoniae in those patients given penicillin
      prophylaxis after 5 years of age (4.1%) compared with those patients given
      placebo after 5 years of age (6.4%). Likewise, there was no significant
      difference (p = 0.298) in the percent of patients with at least one positive
      culture for S. pneumoniae in the group given prophylactic penicillin after 5
      years of age (21.8%) compared with the group given placebo after 5 years of age
      (28.3%). There was no difference between the penicillin and placebo groups in the
      proportion of patients with penicillin intermediate or resistant pneumococci, but
      there was a trend toward increased carriage of multiply drug-resistant
      pneumococci in children > 5 years of age receiving prophylactic penicillin
      compared to children > 5 years of age receiving placebo. The increased
      colonization rate with multiply drug-resistant organisms of children > 5 years of
      age receiving penicillin prophylaxis is not statistically significant.
      CONCLUSIONS: The potential for continued penicillin prophylaxis to contribute to
      the development of multiply resistant pneumococci should be considered before
      continuing penicillin prophylaxis in children with sickle cell anemia who are
      older than 5 years of age. Added to the published data from PROPS II, which
      demonstrated no apparent advantage to continue prophylaxis, the data support the
      conclusion that, for children with no history of invasive pneumococcal disease,
      consideration should be given to discontinue prophylactic penicillin after their
      fifth birthday.

PMID- 9256833
TI  - PET FDG studies of Wilms tumors.
AB  - PURPOSE: Wilms tumor is the most common renal neoplasm in children. The diagnosis
      is usually suggested by anatomic imaging and established by biopsy or resection.
      The principal roles of functional imaging have been the search for skeletal
      metastases and evaluation of renal function. We hypothesized that, like many
      tumors, Wilms tumors could concentrate 18F-FDG and that evaluation of the
      metabolic activity of these neoplasms might prove clinically useful. MATERIALS
      AND METHODS: Three patients with known or suspected Wilms tumors underwent
      positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose
      (FDG) scanning (four scans). A patient with a single Wilms tumor was studied once
      at the time of diagnosis. The two patients with bilateral Wilms tumors were
      studied during therapy. RESULTS: Uptake of FDG was present in the Wilms tumor
      studied at diagnosis, and in one of the tumors in each of the patients with
      bilateral disease studied during therapy. In all three cases, the results of the
      PET scans influenced therapeutic decisions. CONCLUSION: PET FDG scanning may be
      useful for the management of selected patients with Wilms tumors.

PMID- 9256834
TI  - The use of implantable venous access devices (IVADs) in children with hemophilia.
AB  - PURPOSE: Implantable venous access devices (IVADs), either centrally or
      peripherally implanted, have become increasingly popular in children with
      hemophilia to assist in the early treatment of bleeding episodes and in the
      prevention of arthropathy. Their use has been associated with complications
      including thrombosis, thrombophlebitis, and infection. We attempted to better
      define whether the benefits associated with IVADs in this population outweight
      the associated risks. PATIENTS AND METHODS: We studied the medical records of 35
      children from the University of Minnesota's Comprehensive Hemophilia Center who
      received IVADs between 1992 and 1996. RESULTS: There was no bleeding or
      thrombophlebitis associated with IVADs in our population. One patient required
      removal of a central IVAD due to thrombosis. The central IVADs were associated
      with local infection and bacteremia rates of 3% and 33%, respectively. The rates
      of local infection and bacteremia associated with peripheral IVADs were both 25%.
      The majority of infections were cleared with antibiotics, and ports remained
      intact. Both types of IVADs were associated with a high patient/parent
      satisfaction. CONCLUSION: Despite being associated with a significant incidence
      of infection, we believe the benefits of IVADs for children with hemophilia and
      their families outweigh the risks. Possible explanations for the observed
      infection rates are discussed.

PMID- 9256835
TI  - Nephrotic syndrome associated with hypocomplementemia in a 4-year-old boy with
      hemophilia B.
AB  - PURPOSE: The case of a 4-year-old boy with hemophilia B with inhibitor who
      developed nephrotic syndrome is described. The possible association between
      factor IX therapy and nephrotic syndrome in patients with hemophilia B is
      discussed. PATIENT AND METHODS: A chart review of a 4-year-old boy with
      hemophilia B and an inhibitor who developed nephrotic syndrome with transient
      hypocomplementemia was performed. In addition, a literature search was undertaken
      to determine the prevalence of this association and possible etiologic factors.
      RESULTS: Although the nephrotic syndrome was resistant to steroid therapy and
      Bebulin (Osterreichisches Institut fur Haemoderivate Ges.M.B.H., Subsidiary of
      Immuno AG, Vienna, Austria) infusions were continued, the edema resolved and
      proteinuria decreased. Seven month later, proteinuria, accompanied by transient
      hypocomplementemia, increased again. A rise in factor IX inhibitor level was
      observed. The patient received no immunosuppressive therapy, and exhibited a
      continuous decrease in urinary protein excretion over the following months.
      DISCUSSION: A discussion about possible differential diagnoses and a review of
      the literature are presented.

PMID- 9256836
TI  - Successful systemic low-dose lysis of a caval thrombus by rt-PA in a neonate with
      congenital nephrotic syndrome.
AB  - PURPOSE: Thrombotic complications in nephrotic syndrome due to renal loss of
      antithrombin III (AT III) are well known. With this case report, we want to
      demonstrate the possibility of achieving the lysis of such a thrombosis in the
      neonatal period with low-dose rt-PA. PATIENTS AND METHODS: We treated a 10-day
      old newborn who had congenital nephrotic syndrome, who developed a caval
      thrombosis during the first days of his life. After a trial of heparin (up to 20
      IU/kg/hour) over a period of 24 hours and treatment with AT III (2 x 250 IU/day)
      proved to be ineffective, we started systemic thrombolytic therapy with rt-PA. An
      initial bolus of 0.4 mg/kg during 1 hour was followed by an infusion of 0.5
      mg/kg/d rt-PA over a period of 36 hours. Low-dose heparin (5 IU/kg/hour) was
      given simultaneously. Complete clot dissolution could be achieved this way. No
      adverse effects were observed, including no clinical signs of bleeding.
      CONCLUSION: It seems that low-dose rt-PA treatment is safe and effective in
      dissoluting large caval thromboses in neonates.

PMID- 9256837
TI  - Recurrence of childhood acute lymphoblastic leukemia presenting as a tumor of the
      middle ear: a case report.
AB  - PURPOSE: Extramedullary relapse of childhood acute lymphoblastic leukemia most
      commonly occurs in the central nervous system or in the testes. Otologic
      involvement is very rare and has only been reported as an autopsy finding.
      PATIENT AND METHODS: We describe the case of a 5-year-old girl with CD10 positive
      acute lymphoblastic leukemia (ALL) who developed an isolated otologic relapse 18
      months after the initial diagnosis of ALL. RESULTS: This otologic relapse
      presented as an atypical otitis media related to a mass of the middle ear. The
      leukemic infiltration of the middle ear was demonstrated by histologic
      examination. A cytogenetic change characterized by the occurrence of
      t(1;19)(q23;p13) was observed in the leukemic cells from the middle ear, and the
      t(1;19) molecular fusion transcript E2A-PBX1 was detected in the bone marrow by
      polymerase chain reaction. CONCLUSION: The ear is an exceedingly rare site of
      relapse in children with acute lymphoblastic leukemia. Molecular analysis
      demonstrates that such an extramedullary relapse can represent an early
      manifestation of systemic relapse.

PMID- 9256838
TI  - Essential thrombocythemia in a 5-month-old infant.

PMID- 9256839
TI  - Predictors of decline in manual performance in older adults.
AB  - OBJECTIVE: To determine factors that predict decline in manual performance using
      a multivariate model of determinants of functional limitation. DESIGN:
      Longitudinal observational study. SETTINGS: Ambulatory general medicine clinics,
      residences of homebound individuals, and a continuing care retirement community.
      PARTICIPANTS: Subjects were 485 persons more than 60 years of age and included
      continuing care retirement community (CCRC) residents (n = 215), chronically
      homebound older persons (n = 65), and ambulatory older adults (n = 205). Mean age
      at baseline was 78 years. MEASUREMENT: Independent variables included
      demographics, physician measures of upper-extremity joint impairment,
      comorbidities derived from physical examination and chart abstract, self-assessed
      arthritis pain, depression, and anxiety. The major dependent variable was 2-year
      decline in timed manual performance below a threshold associated with need for
      long-term care services. RESULTS: The proportion of subjects who exceed a Timed
      Manual Performance Test threshold of 350 seconds increased slowly from baseline
      through Year 4 for all age groups but rose rapidly from Year 4 to Year 6 for the
      oldest group (> 85 years at baseline). Using a discrete survival model, we found
      that age, education, grip strength, and psychological status predicted crossing
      the manual performance threshold within a 2-year period. CONCLUSIONS: The
      findings, coupled with earlier findings that upper extremity joint impairment
      predicted both grip strength and manual performance, suggest that joint
      impairment may be an important risk factor for future functional limitation.
      Since diminished hand function has been shown to predict dependency, development
      and testing of interventions to maintain or restore upper extremity joint
      function and reduce pain would appear to be a high research priority.

PMID- 9256840
TI  - Medical practice with nursing home residents: results from the National Physician
      Professional Activities Census.
AB  - OBJECTIVE: The study describes the prevalence of medical nursing home practice.
      Further, it examines the extent to which physician characteristics and local
      county health care resources predict nursing home involvement. This information
      is relevant to evaluating and devising strategies that address the future
      provision of medical care in institutionalized long-term care. DESIGN: A cross
      sectional survey. SETTING: A national sample of all licensed practicing
      physicians was obtained from a special Professional Activities (PPA) survey
      conducted by the American Medical Association (AMA) in 1991. PARTICIPANTS:
      Respondents were 21,578 physicians involved in direct patient care. MEASURES: The
      typical number of hours spent weekly caring for nursing home patients was
      obtained from the PPA survey, and physician demographics were obtained from the
      AMA Masterfile. County health care resources were obtained from the National
      Institutes of Health Area Resources File. RESULTS: Most (77%) physicians reported
      spending no measurable time caring for nursing home patients. In all disciplines,
      a majority of physicians with a nursing home practice spent less than 2 hours per
      week with patients. Logistic regressions indicted that family practitioners and
      internists were most likely to have a nursing home practice, but general
      practitioners were most likely to spend more time in practice. Only 15% of
      specialists reported having a nursing home practice. Prevalence of practice was
      greatest among solo practitioners and physicians in partnerships and least among
      academic and hospital-based physicians and physicians in group practice or
      employed by the government. Most county of practice resources were not associated
      or were modestly associated with nursing home practice, but having a nursing home
      practice became much more likely as the number of nursing home residents
      increased and hospital beds decreased. A pattern was found for nursing home
      practice to be slightly less likely as the county's per capita income and the
      proportion of proprietary nursing facilities increased. CONCLUSIONS: With
      increasing numbers of older and frailer residents, nursing homes will continue to
      be integral components of the future healthcare system. However, physicians
      currently spend minimal time caring for nursing home patients, with physician
      characteristics best predicting involvement. Questions remain about the future of
      nursing home medical practice and how to best recruit, staff, and train future
      cadres of physicians to provide sufficient quality care for nursing home patients
      in an evolving health care system.

PMID- 9256841
TI  - Diuretic usage and withdrawal patterns in a Dutch geriatric patient population.
AB  - OBJECTIVES: To describe diuretic usage and withdrawal patterns in a population of
      very old geriatric patients and to evaluate the long-term probability of
      remaining free from diuretic therapy after withdrawal. DESIGN: Retrospective
      analysis of medical records and 1-year follow-up study. SETTING: University
      Hospital Nijmegen and Rijnstate Hospital Arnhem, a non-academic teaching
      hospital, The Netherlands. PARTICIPANTS: All 1547 patients, aged 75 years or
      older, visiting geriatric medicine departments in the two hospitals for the first
      time in the years 1990 through 1993. MEASUREMENTS: Data on medical history,
      physical examinations, and medication use were obtained from medical records.
      Diuretic withdrawal and motivation was recorded as reported. Record review
      indicating diuretic withdrawal prompted a 1-year follow-up investigation and
      collection of additional updated information from family care and/or nursing-home
      physicians. RESULTS: A total of 593 three patients (38.3%) were using diuretics.
      Use of diuretics increased with age from 33.6% in patients aged 75 to 79 years to
      47.4% in patients aged 90 years or older (P < .05). Diuretics were withdrawn in
      218 patients (36.8%), in 101 patients because of doubts about the initial or
      persistent indication for diuretic use and in 91 patients because of adverse
      effects. No reasons for withdrawal were reported in 26 patients. Withdrawal of
      diuretics was attempted more often in cases of diuretic prescriptions for unknown
      reasons (51.2%) or ankle edema without heart failure (45.0%) than when
      prescriptions were for heart failure (28.5%) or hypertension (35.4%). The overall
      probability of remaining free of diuretic therapy for 1 year was 0.41. Success of
      diuretic withdrawal was significantly less when congestive heart failure was the
      initial indication for prescription (probability 0.24). We did not find other
      clinical parameters related to the success of withdrawal. CONCLUSIONS: Our study
      demonstrates that diuretic therapy can be withdrawn for at least a 1-year period
      in a substantial number of very old geriatric patients receiving these
      medications, regardless of the initial indications for prescription. However,
      withdrawal is performed without application of uniform criteria. Future
      prospective studies should be directed at developing clear guidelines for
      diuretic withdrawal in order to facilitate identification of eligible patients
      and to further improve the success of withdrawal attempts.

PMID- 9256842
TI  - Eligibility of Alzheimer's disease clinic patients for clinical trials.
AB  - OBJECTIVES: To identify the percentage of patients with Alzheimer's disease (AD)
      in a general clinic population who would be provisionally eligible for randomized
      clinical trials and the extent to which these patients represent the overall
      clinic-based population. BACKGROUND: Many randomized clinical trials have
      restricted enrollment criteria that may limit generalizability, i.e., AD patients
      who fulfill selection criteria for phase III clinical trials may not be
      representative of other AD patients in clinical settings. DESIGN AND SETTING:
      Patients diagnosed as probable or possible AD from the nine clinical sites of the
      State of California's Alzheimer's Disease Diagnostic and Treatment Centers
      (ADDTC) were selected on the basis of their provisionally fulfilling the
      inclusion and exclusion criteria of two typical AD clinical trials at the time of
      their first visit (ECG and brain imaging criteria were not available). RESULTS:
      From a sample of 3470 subjects with possible or probable AD, overall, only 4.4%
      or 7.9% would have been provisionally eligible for each of two trials. Patients
      provisionally eligible were younger, relatively underrepresented by women, better
      educated, wealthier, and more likely to be white than ineligible patients. The
      major independent demographic predictors for eligibility were (1) income greater
      than $15,000 per year, (2) male gender, and (3) college education. More than 60%
      of probable AD patients were excluded because of significant behavioral problems;
      approximately one-quarter each were excluded because of significant medical or
      neurological problems. Allowing patients with probable or possible AD to enroll
      would have resulted in 10.6% being eligible. CONCLUSION: Selection criteria for
      AD clinical trials result in a demographically and clinically constrained
      subgroup that is not representative of the overall clinic population.

PMID- 9256843
TI  - Proxies' decisions about clinical research participation for their charges.
AB  - OBJECTIVE: To examine the process by which proxies decide about their charges'
      participation in clinical research. DESIGN: Using eight hypothetical research
      studies encompassing a variety of risks and benefits, we interviewed 315
      competent persons > or = 65 years old (charges) and, separately, the individuals
      who would be designated as their proxies if the charges were to become
      incompetent. The proxies were asked what they thought their charges would decide
      and what decisions they would make for their charges and for their own
      participation. SETTINGS: A medical house-call program, two apartment complexes,
      and three nursing homes. PARTICIPANTS: Charges > or = 65 years old and their
      proxies. MAIN OUTCOME MEASURE: Comparison of decisions made by charges and by
      proxies for their charges. RESULTS: The agreement between the proxies' and
      charges' decisions was not significantly different from random agreement (range
      of kappa statistics, 0.05-0.15). Rather, proxies' decisions for their charges
      were significantly related to the proxies' decisions for themselves (kappas, 0.52
      0.86). When the paired proxies' and charges' decisions differed, the proxies were
      protective, more frequently refusing their charges' participation in the
      perceived riskier research studies. CONCLUSIONS: Proxies did not know what their
      charges would decide. Their choices for the charges related more to the proxies'
      decisions about their own participation (which they knew) than to the decisions
      of their charges (which they didn't know). This is similar to the process of a
      reasonable person making the decision, a characteristic of decisions made in the
      best interests of the patient.

PMID- 9256844
TI  - Clinical trial participant satisfaction: survey of SHEP enrollees. SHEP
      Cooperative Research Group. Systolic Hypertension in the Elderly Program.
AB  - OBJECTIVE: The purpose of this study was to determine older persons' reasons for
      joining a clinical trial, and to provide data that could be useful in planning
      and carrying out clinical trials in older and minority populations. DESIGN: A
      survey. PARTICIPANTS: The sample included 4281 men and women 60 years of age or
      older who were randomized to the Systolic Hypertension in the Elderly Program
      (SHEP). MEASUREMENTS: A 10-item satisfaction/attitude questionnaire was designed
      to evaluate (1) what personal benefits people expect from participation in this
      trial, (2) motivation for joining, and (3) satisfaction with clinic staff and
      operations. Each question had a response category asking for a measure of
      agreement, satisfaction, or importance. RESULTS: The most important reasons for
      joining the clinical trial were to contribute to science (96%), improve the
      health of others (96%), and improve their own health (93%). Free medical care and
      social aspects were less important reasons to join. There were no differences by
      treatment assignment, but differences in reasons for joining SHEP by age, race,
      gender, and education were observed. CONCLUSION: Older adults were enthusiastic
      about clinical trial participation. Recruitment, participant management
      strategies, and allocation of resources should consider the needs of specific
      patient groups.

PMID- 9256846
TI  - Adverse drug events in high risk older outpatients.
AB  - OBJECTIVE: To describe the prevalence, types, and consequences of adverse drug
      events (ADEs) in older outpatients with polypharmacy. DESIGN: A cohort study.
      SETTING: General Medicine Clinic at the Durham Veterans Affairs Medical Center.
      PATIENTS: A total of 167 high risk (taking > or = 5 scheduled medications)
      ambulatory older veterans who participated in a year long health service
      intervention trial. MEASUREMENTS: Potential ADEs were identified by asking
      patients during closeout interviews whether, in the past year, they had
      experienced any side effects, unwanted reactions, or other problems from any
      medication. All reported medications and corresponding adverse experiences were
      assessed for plausibility by a research clinical pharmacist using two standard
      pharmacological textbooks and categorized by predictability, therapeutic class,
      and organ system. RESULTS: Eighty self-reported ADEs involving 72 medications
      taken by 58 (35%) of 167 patients were textbook confirmed. Seventy-six of 80
      (95%) ADEs were classified as Type A (predictable) reactions. Cardiovascular
      (33.3%) and central nervous system (27.8%) medication classes were most commonly
      implicated. Gastrointestinal (30%) and central nervous system (28.8%) ADE
      symptoms were common. Sixty-three percent of patients with ADEs required
      physician contacts, 10% emergency room visits, and 11% hospitalization. Twenty
      percent of medications implicated with ADEs required dosage adjustments, and 48%
      of ADE-related medications were discontinued. No significant differences (P >
      .05) were observed when ADE reporters (n = 58) and nonreporters (n = 109) were
      compared. CONCLUSION: Predictable ADEs are common in high risk older outpatients,
      resulting in considerable medication modification and substantial healthcare
      utilization.

PMID- 9256845
TI  - Changes in advance care planning in nursing homes before and after the patient
      Self-Determination Act: report of a 10-state survey.
AB  - OBJECTIVE: The Patient Self-Determination Act (PSDA) implemented in 1991 has
      focused national attention on the right of patients to be involved in decision
      making and on the use of written advance directives. We report changes in advance
      care planning with the PSDA and other historical events in nursing homes in 10
      states. DESIGN: Pre- and Post-observational cohort study. PATIENTS: Nursing home
      residents, residing in 270 long-term care facilities in 10 states, stratified to
      ensure representation of urban and rural facilities in each state. In 1990, 2175
      patients were sampled, and 2088 different patients from the same facilities were
      sampled in 1993. Six-month follow-up was obtained at both time periods. MAIN
      OUTCOME MEASURES: Advance care planning was defined as the documentation in the
      medical record of a living will, a durable power of attorney, a "Do Not
      Resuscitate" (DNR) order, a "Do Not Hospitalize" (DNH) order, or an order to
      forgo artificial nutrition or hospitalization. RESULTS: The rate of chart
      documentation of living wills increased from 4.2% in 1990 to 13.3% in 1993, and
      DNR orders increased dramatically from 31.1% to 51.5%. The rates of DNH and
      orders to forgo artificial hydration and nutrition remained less than 8% in both
      years. We found striking variations in advance care planing among the 10 states.
      In 1990, having a DNR order varied from 10.1% to 69.2% across the 10 states. With
      the exception of Oregon, where 69.2% of patients already had a DNR order, the
      states saw a 1.5 to 3.1 times increase in the rate of DNR orders in 1993 compared
      with 1990. CONCLUSION: With the implementation of the PSDA, there was modest
      increase in documentation of living wills, but DNH and orders to forgo artificial
      hydration and nutrition remained the same. There was a substantial increase in
      DNR orders that began before the PSDA implementation. This increase was
      associated both with the implementation of the PSDA and the increased debate
      about the appropriateness of CPR for nursing home residents. This increase varied
      considerably among geographic areas from the 10 states. Future research is needed
      to understand this geographic variation.

PMID- 9256847
TI  - Alzheimer's disease and driving: prediction and assessment of driving
      performance.
AB  - OBJECTIVES: To examine driving competence in a group of drivers diagnosed with
      probable Alzheimer's Disease (AD) in terms of a standardized open road evaluation
      and expert judgments. To examine the validity of a standardized medical
      examination, including administration of the Mini-Mental Status Exam (MMSE), and
      a standardized neuropsychological assessment as predictors of open road driving
      performance. DESIGN: A prospective investigation with consecutively referred
      subjects. SETTING: Coorabel Driver Assessment Centre, Royal Rehabilitation Centre
      Sydney, Australia. PARTICIPANTS: Nineteen subjects with a diagnosis of probable
      AD. MEASUREMENTS: A standardized clinical medical examination, a standardized
      neuropsychological assessment, and a standardized open road driving evaluation.
      The driving evaluation provided a correct driving actions score. The outcome
      measure was the expert judges' rating of overall driving competence, which was
      termed the final on-road result. RESULTS: Seven subjects passed the on-road
      driving evaluation, and 12 failed. MMSE was found to be a significant predictor
      of final on-road result. The physician's prediction, the neuropsychology test
      scores, and the neuropsychologist's prediction were not found to be significantly
      associated with the final on-road result. The on-road driving evaluation was a
      reliable test. CONCLUSION: Inasmuch as all subjects except one were still driving
      and all wished to continue to drive, it is important to note that 63.2% of
      subjects failed the on-road evaluation. Conversely, 36.8% were judged safe to
      drive, suggesting that AD diagnosis alone may be insufficient criteria for
      cessation of driving. A standardized road test may be the only appropriate means
      of determining driving competence in people diagnosed with AD.

PMID- 9256848
TI  - The relationship between self-rated health and depressive symptoms in an
      epidemiological sample of community-dwelling older adults.
AB  - OBJECTIVE: To confirm the association between depression and self-rated general
      health, independent of demographics, functional disability, physical illness
      burden, and health services utilization. DESIGN: Logistic regression analyses of
      data obtained in a cross-sectional epidemiological survey. SETTING: The mid
      Monongahela Valley, a rural, nonfarm, low SES community. PARTICIPANTS: Random
      sample of 880 subjects aged 65 and older. MEASUREMENTS: The dependent variable
      was self-rated overall health, categorized as excellent, good, fair, or poor. The
      independent variables were demographics (age, gender, education), number of
      depressive symptoms, number of impaired instrumental activities of daily living
      (IADLs), measures of physical illness burden (individual medical conditions,
      number of affected organ systems or disease processes, and number of prescription
      medications), and measures of health services utilization (number of visits to
      physicians, and acute hospitalization). RESULTS: Univariate analyses indicated
      that poorer self-rated health was associated with lesser education, higher
      numbers of depressive symptoms, impaired IADLs, prescription medications,
      physician visits, hospitalizations, and affected organ systems, and with the
      presence of several specific conditions. However, multiple logistic regression
      analyses revealed that only the following variables were associated independently
      with poorer self-rated health: age less than 75 years, education less than high
      school graduation, greater numbers of depressive symptoms, impaired IADLs,
      prescription medications, and physician visits. CONCLUSIONS: Even when
      controlling for physical illness and functional disability, subjective rating of
      overall health remains strongly and independently associated with depressive
      symptoms.

PMID- 9256849
TI  - Preadipocyte function and aging: links between age-related changes in cell
      dynamics and altered fat tissue function.
AB  - OBJECTIVE: To review recent findings about changes with age in the replication
      and differentiation of preadipocytes, the progenitor cells in fat tissue that are
      capable of differentiating into fat cells, and to examine possible links between
      these alterations and age-related changes in fat tissue function. DESIGN: A
      survey and analysis of recent literature concerning changes in preadipocyte and
      fat cell function with age. CONCLUSIONS: Intrinsic aging changes in fat cells and
      preadipocytes as well as in factors extrinsic to fat tissue (such as food intake
      and absorption and hormonal status) contribute to age-related alterations in fat
      tissue function and cellularity. Changes with age in preadipocyte number,
      replicative potential, and capacity for differentiation, which may be linked to
      aging changes in fat cell size, number, and function, have been identified. The
      decline in preadipocyte capacity for differentiation and the associated decline
      in fat cell lipogenic capacity may be particularly important in contributing to
      the decrease in fat mass and alterations in fat tissue function that occur
      between middle- and old age. These declines result from blunting of the changes
      in gene expression that occur during preadipocyte differentiation and may, in
      turn, be related to altered regulation of particular transcription factors that
      control the preadipocyte differentiation program and maintenance of fat cell
      function.

PMID- 9256850
TI  - Epidemiology, pathophysiology, and etiology of congestive heart failure in older
      adults.
AB  - OBJECTIVES: To review the epidemiology, pathophysiology, and etiology of
      congestive heart failure (CHF) in older adults. METHODS: Published reports
      relevant to the epidemiology, pathophysiology, and etiology of CHF were
      systematically reviewed. Studies involving older adults and more recent studies
      were emphasized. RESULTS: More than 75% of patients with CHF in the United States
      are older than 65 years of age, and CHF is the leading cause of hospitalization
      in older adults. CHF is also a major cause of chronic disability, and annual
      expenditures for CHF currently exceed $10 billion. In addition, both the
      incidence and prevalence of CHF are increasing, largely as a result of the aging
      of the population. Older adults are predisposed to developing CHF as a result of
      age-related changes in the cardiovascular system and the high prevalence of
      hypertension, coronary artery disease, and valvular heart disease in this age
      group. Although the fundamental pathophysiology of CHF is similar in younger and
      older patients, older individuals are more prone to develop CHF in the setting of
      preserved left ventricular systolic function. This syndrome, referred to as
      diastolic heart failure, accounts for up to 50% of all cases of CHF in adults
      more than 65 years of age. Coronary heart disease and hypertension are the most
      common etiologies of CHF in older adults, and they often coexist. Valvular heart
      disease, especially aortic stenosis and mitral regurgitation, are also common in
      older adults, whereas nonischemic dilated cardiomyopathy, hypertrophic
      cardiomyopathy, and restrictive cardiomyopathy occur less frequently.
      CONCLUSIONS: Congestive heart failure is a major public health problem in the
      United States today as a result of its high and increasing prevalence in the
      older population as well as its substantial impact on healthcare costs and
      quality of life. There is an urgent need to develop more effective strategies for
      the prevention and treatment of CHF in older individuals.

PMID- 9256851
TI  - The Resident Assessment Instrument (RAI): promise and pitfalls.

PMID- 9256852
TI  - The OBRA-87 nursing home regulations and implementation of the Resident
      Assessment Instrument: effects on process quality.
AB  - OBJECTIVE: To characterize changes in key aspects of process quality received by
      nursing home residents before and after the implementation of the national
      nursing home Resident Assessment Instrument (RAI) and other aspects of the
      Omnibus Budget Reconciliation Act (OBRA) nursing home reforms. DESIGN: A quasi
      experimental study using a complex, multistage probability-based sample design,
      with data collected before (1990) and after (1993) implementation of the RAI and
      other OBRA provisions. SETTING AND PARTICIPANTS: Two independent cohorts (n >
      2000) of residents in a random sample of 254 nursing facilities located in
      metropolitan statistical areas in 10 states. INTERVENTION: OBRA-87 enhanced the
      regulation of nursing homes and included new requirements on quality of care,
      resident assessment, care planning, and the use of neuroleptic drugs and physical
      restraints. One of the key provisions, used to help implement the OBRA
      requirements in daily nursing home practice, was the mandatory use of a
      standardized, comprehensive system, known as the RAI, to assist in assessment and
      care planning. OBRA provisions went into effect in federal law on October 1,
      1990, although delays issuing the regulations led to actual implementation of the
      RAI during the Spring of 1991. MEASUREMENTS AND ANALYSES: Research nurses spent
      an average of 4 days per facility in each data collection round, assessing a
      sample of residents, collecting data through interviews with and observations of
      residents, interviews with multiple shifts of direct staff caregivers for the
      sampled residents, and review of medical records, including physician's orders,
      treatment and care plans, nursing progress notes, and medication records. The RNs
      collected data on the characteristics of the sampled residents, on the care they
      received, and on facility practices. The effect of being a member of the 1990 pre
      OBRA or the 1993 post-OBRA cohort was assessed on the accuracy of information in
      the residents' medical records, the comprehensiveness of care plans, and on other
      key aspects of process quality while controlling for any changes in resident case
      mix. The data were analyzed using contingency tables and logistic regression and
      a special statistical software (SUDAAN) to assure proper variance estimation.
      RESULTS: Overall, the process of care in nursing homes improved in several
      important areas. The accuracy of information in residents' medical records
      increased substantially, as did the comprehensiveness of care plans. In addition,
      several problematic care practices declined during this period, including use of
      physical restraints (37.4 to 28.1% (P < .001)) and indwelling urinary catheters
      (9.8 to 7% (P < .001)). There were also increases in good care practices, such as
      the presence of advanced directives, participation in activities, and use of
      toileting programs for residents with bowel incontinence. These results were
      sustained after controlling for differences in the resident characteristics
      between 1990 and 1993. Other practices, such as use of antipsychotic drugs,
      behavior management programs, preventive skin care, and provision of therapies
      were unaffected, or the differences were not statistically significant, after
      adjusting for changes in resident case-mix. CONCLUSION: The OBRA reforms and
      introduction of the RAI constituted an unprecedented implementation of
      comprehensive geriatric assessment in Medicare- and Medicaid-certified nursing
      homes. The evaluation of the effects of these interventions demonstrates
      significant improvements in the quality of care provided to residents. At the
      same time, these findings suggest that more needs to be done to improve process
      quality. The results suggest the RAI is one tool that facility staff, therapists,
      pharmacy consultants, and physicians can use to support their continuing efforts
      to provide high quality of care and life to the nation's 1.7 million nursing home
      residents.

PMID- 9256853
TI  - Association of the Resident Assessment Instrument (RAI) with changes in function,
      cognition, and psychosocial status.
AB  - OBJECTIVE: To evaluate the impact of the Resident Assessment Instrument (RAI) on
      changes in nursing home residents' functional status, cognitive status, and
      psychosocial well-being. DESIGN: A quasi-experiment involving the collection of
      longitudinal data on two cohorts of nursing home residents. One cohort was
      assessed before the implementation of the RAI, and the other was assessed after
      the implementation of the new assessment process. SETTING AND PARTICIPANTS: Over
      2000 nursing home residents in 267 nursing homes located in 10 geographic areas
      were assessed during the pre-RAI period. In the post-RAI period, 2000 new
      residents in 254 of the same facilities were assessed. INTERVENTION: RAI
      implementation began in October 1990 and continued until October 1991. The RAI
      includes a structured, multidimensional resident assessment and problem
      identification system designed to form the basis for residents' care plans.
      MEASUREMENTS: All residents were assessed at baseline and at 6 months using the
      Minimum Data Set for Nursing Home Resident Assessment and Care Screening (MDS)
      and its protocols. All data were collected by research nurses employed and
      trained by the research team. RESULTS: Implementation of the RAI significantly
      reduced the rate of decline in seven of the nine outcomes under consideration.
      Reductions in improvement were also observed in all outcomes. In activities of
      daily living, social engagement, and cognitive function, the reduced decline far
      outweighed any reductions in improvement. In mood problems, problem behaviors,
      and understanding others, however, reductions in improvement were greater than
      any reductions in decline. Changes in the rates of decline and improvement were
      not uniform across all residents. CONCLUSION: The RAI may have improved the
      quality of care of nursing home residents by reducing overall rates of decline in
      important areas of resident function. However, this innovation may have generated
      trade-offs in that it may have reduced improvement rates in some areas of
      function. The system's implementation also seems to have focused staff's
      attention on the needs and strengths of specific subpopulations of residents.
      Revisions of the RAI must assist staff in generalizing their efforts to all
      residents and to increasing improvement rates, especially in areas related to
      mood and behavior.

PMID- 9256854
TI  - Effect of the National Resident Assessment Instrument on selected health
      conditions and problems.
AB  - OBJECTIVE: To evaluate the effect of the implementation of the National Resident
      Assessment Instrument (RAI) system on selected conditions representing outcomes
      for nursing home residents. DESIGN: Quasi-experimental, pre-/post-design, with
      assessments at baseline and 6-month follow-up. SAMPLE: Two thousand one hundred
      twenty-eight residents from 268 nursing homes in 10 states before RAI
      implementation, and 2,088 from 254 of the same nursing homes after
      implementation. MEASURES: From the full RAI Minimum Data Set, measures of
      dehydration, falls, decubitus, vision problems, stasis ulcer, pain, dental status
      (poor teeth), and malnutrition were examined at baseline and 6 months later. Poor
      nutrition was evaluated using a body mass index score below 20 and vision using a
      4-level scale; other conditions were represented by their presence or absence.
      Decline and improvement were computed as the changes in level between baseline
      and follow-up, limiting the sample to those who could manifest each such change.
      MAIN RESULTS: Of eight health conditions representing poorer health status,
      dehydration and stasis ulcer had significantly lower prevalence after the
      implementation of the RAI (1993) compared with 1990. At the same time, there was
      an increase in the prevalence of daily pain. Fewer residents declined over 6
      months in nutrition and vision after implementation. Although for these two
      conditions there were also significantly reduced rates of improvement, the net
      was an overall reduction in the 6-month rate of decline for all residents. Pain
      also demonstrated a decline in the postimplementation rate of improvement. The
      combined eight conditions showed reductions in the rates of both decline and
      improvement. CONCLUSIONS: Several outcomes for nursing home residents improved
      after implementation of the RAI. Of the four conditions for which there are
      significant declines in prevalence or outcome changes, three are specifically
      addressed in the care planning guidelines incorporated the RAI system (all except
      stasis ulcer, although there is a RAP for decubitus ulcer). Pain, the only other
      condition with a significant result --an increase in baseline prevalence--also
      has no RAP. Although the changes might be ascribed otherwise, they support the
      premise that the RAI has directly contributed to improved outcomes for nursing
      home residents.

PMID- 9256855
TI  - Changes in hospitalization associated with introducing the Resident Assessment
      Instrument.
AB  - OBJECTIVE: To compare the rates of hospitalization among cohorts of nursing home
      residents assembled before and after the implementation of the federally mandated
      Resident Assessment Instrument (RAI). SAMPLE: Subjects were nursing home
      residents chosen from 268 facilities in major Metropolitan Statistics Areas in 10
      states and representing more than 1500 facilities and 60,000 residents. Two
      resident cohorts (1990 and 1993) were sampled (8 to 16 residents per facility,
      depending upon facility size) as part of an evaluation of the impact of
      implementing the RAI. METHODS: Research nurses reviewed records, interviewed
      staff, observed patients, and completed an RAI at baseline and 6 months later.
      All transitions during this interval (hospital admissions, nursing home
      transfers, returns home, death, etc.) were tracked. Using polytomous logistic
      regression, we tested the effect of cohort on the probability of being
      hospitalized in light of the competing risks of dying or remaining in the home,
      controlling for demographic and casemix variables, and having a DNR order in the
      chart. RESULTS: A total of 4196 residents were studied, 2118 in 1990 (age 81.3,
      female 77.7%, LOS 6+ months 49.8%) and 2078 in 1993 (age 81.7, females 75.5%, LOS
      6+ months 50.2%). The unadjusted probability of hospitalization dropped from .205
      to .151. Multivariate analyses revealed a significant adjusted odds of
      hospitalization of .74 (95% CI .60-.91) and no cohort effect on home discharge or
      death. Among severely cognitively impaired residents, the adjusted odds of
      hospitalization in 1993 compared with the 1990 cohort was 0.74 (.53-1.03).
      Finally, among survivors in both cohorts who had a follow-up MDS performed, and
      whose ADL remained stable, 15.9% were hospitalized in 1990, whereas only 10.9%
      were hospitalized in 1993. On the other hand, ADL decliners were more likely to
      have been hospitalized in 1993 than in 1990 (40.6% vs 25.2%). CONCLUSIONS:
      Although other changes in the industry, clinical practice, and health care policy
      may have influenced hospitalization of nursing home residents, the substantial
      reductions observed among the cognitively impaired and those with stable ADL
      suggest superior and uniform assessment information in the form of the RAI
      contributed significantly to this decline.

PMID- 9256856
TI  - A commitment to change: revision of HCFA's RAI.
AB  - OBJECTIVE: To describe the reliability of new assessment items and their clinical
      utility as judged by experienced nurse assessors, based on the results from the
      field test of Version 2.0 of the Resident Assessment Instrument (RAI). DESIGN:
      Independent dual assessment of residents of nursing facilities by staff nurses
      using a draft of Version 2.0 of the minimum data set (MDS). SETTING AND
      PARTICIPANTS: A total of 187 randomly selected residents from 21 nursing homes in
      seven states volunteered to test Version 2.0 of the MDS. MEASUREMENT: The full
      array of MDS assessment items included measures in the following areas:
      Background information, cognitive patterns, communication/hearing, vision, mood
      and behavior, psychosocial well-being, physical functioning and structural
      problems, continence, disease diagnoses, health condition, oral/nutritional
      status, dental status, skin condition, activity pursuit patterns, medications,
      special treatments and procedures, and discharge potential and overall status.
      RESULTS: Evaluative data address issues of MDS item utility and reliability. For
      new items, almost all achieved a reasonably high-weighted Kappa interrater
      reliability; revised items also surpassed earlier items, and with the updated
      training materials, even the non-changed items had higher average reliability
      levels. Based on the success of the field test and the positive response of the
      industry, Version 2.0 of the RAI has been adopted, and HCFA has initiated a more
      long-range process to update further the RAI when necessary. CONCLUSION: Findings
      support the reliability and clinical utility of the new and revised assessment
      items incorporated by HCFA in Version 2.0 of the MDS.

PMID- 9256857
TI  - Comprehensive clinical assessment in community setting: applicability of the MDS
      HC.
AB  - OBJECTIVE: To describe the results of an international trial of the home care
      version of the MDS assessment and problem identification system (the MDS-HC),
      including reliability estimates, a comparison of MDS-HC reliabilities with
      reliabilities of the same items in the MDS 2.0 nursing home assessment
      instrument, and an examination of the types of problems found in home care
      clients using the MDS-HC. DESIGN: Independent, dual assessment of clients of home
      care agencies by trained clinicians using a draft of the MDS-HC, with additional
      descriptive data regarding problem profiles for home care clients. SETTING AND
      PARTICIPANTS: Reliability data from dual assessments of 241 randomly selected
      clients of home care agencies in five countries, all of whom volunteered to test
      the MDS-HC. Also included are an expanded sample of 780 home care assessments
      from these countries and 187 dually assessed residents from 21 nursing homes in
      the United States. MEASUREMENTS: The array of MDS-HC assessment items included
      measures in the following areas: personal items, cognitive patterns,
      communication/hearing, vision, mood and behavior, social functioning, informal
      support services, physical functioning, continence, disease diagnoses health
      conditions and preventive health measures, nutrition/hydration, dental status,
      skin condition, environmental assessment, service utilization, and medications.
      RESULTS: Forty-seven percent of the functional, health status, social
      environment, and service items in the MDS-HC were taken from the MDS 2.0 for
      nursing homes. For this item set, it is estimated that the average weighted Kappa
      is .74 for the MDS-HC and .75 for the MDS 2.0. Similarly, high reliability values
      were found for items newly introduced in the MDS-HC (weighted Kappa = .70).
      Descriptive findings also characterize the problems of home care clients, with
      subanalyses within cognitive performance levels. CONCLUSION: Findings indicate
      that the core set of items in the MDS 2.0 work equally well in community and
      nursing home settings. New items are highly reliable. In tandem, these
      instruments can be used within the international community, assisting and
      planning care for older adults within a broad spectrum of service settings,
      including nursing homes and home care programs. With this community-based, second
      generation problem and care plan-driven assessment instrument, disability
      assessment can be performed consistently across the world.

PMID- 9256858
TI  - Where's Gertrude?

PMID- 9256859
TI  - Can nursing homes use the MDS to improve quality?

PMID- 9256860
TI  - Just another uphill battle for the field of geriatrics.

PMID- 9256861
TI  - Traffic dangerous drugs are often found in fatally injured older male drivers.

PMID- 9256862
TI  - Psychotic symptoms in dementia and the rate of cognitive decline.

PMID- 9256863
TI  - J-curve relation between blood pressure and decline in cognitive function in
      older people living in community, Japan.

PMID- 9256864
TI  - Rehabilitation of the older amputee.

PMID- 9256865
TI  - Nortriptyline for the treatment of depression in progressive supranuclear palsy.

PMID- 9256866
TI  - Lesch-Nyan syndrome in an Alzheimer's disease patient: a case report.

PMID- 9256867
TI  - It is our choice!

PMID- 9256868
TI  - A randomized, controlled clinical trial of a treatment for shoulder pain.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate the efficacy of a
      physical therapy approach to the treatment of shoulder pain. Subjects. Sixty-six
      volunteers with shoulder pain believed to be of local mechanical origin were
      randomly allocated to either a treatment group or a control group. METHODS:
      Subjects in the treatment group received 1 month of physical therapy aimed at
      restoring function of their shoulder muscles. Subjects in the control group
      received no treatment. Outcome measurements of pain intensity, range of motion
      (ROM), isometric muscle force, functional impairment, and self-perception of
      improvement were obtained by blinded assessment. RESULTS: Subjects in the
      treatment group showed improvement in pain-free abduction and flexion ROM,
      functional impairment, and self-perception of improvement. The control group
      deteriorated slightly over the experimental period in ROM and functional
      impairment measures. CONCLUSION AND DISCUSSION: These results suggest that the
      physical therapy approach used in this study is effective in improving shoulder
      function in subjects experiencing pain of mechanical origin. The results also
      provide little evidence of spontaneous recovery over a 1-month period.

PMID- 9256869
TI  - Predicting the probability for falls in community-dwelling older adults.
AB  - BACKGROUND AND PURPOSE: The objective of this retrospective case-control study
      was to develop a model for predicting the likelihood of falls among community
      dwelling older adults. SUBJECTS: Forty-four community-dwelling adults (> or = 65
      years of age) with and without a history of falls participated. METHODS: Subjects
      completed a health status questionnaire and underwent a clinical evaluation of
      balance and mobility function. Variables that differed between fallers and
      nonfallers were identified, using t tests and cross tabulation with chi-square
      tests. A forward stepwise regression analysis was carried out to identify a
      combination of variables that effectively predicted fall status. RESULTS: Five
      variables were found to be associated with fall history. These variables were
      analyzed using logistic regression. The final model combined the score on the
      Berg Balance Scale with a self-reported history of imbalance to predict fall
      risk. Sensitivity was 91%, and specificity was 82%. CONCLUSION AND DISCUSSION: A
      simple predictive model based on two risk factors can be used by physical
      therapists to quantify fall risk in community-dwelling older adults.
      Identification of patients with a high fall risk can lead to an appropriate
      referral into a fall prevention program. In addition, fall risk can be used to
      calculate change resulting from intervention.

PMID- 9256871
TI  - Inspiratory muscle training in patients with chronic heart failure awaiting
      cardiac transplantation: results of a pilot clinical trial.
AB  - BACKGROUND AND PURPOSE: Persons with chronic heart failure (HF) have poor
      ventilatory muscle strength, and this weakness is associated with dyspnea. The
      purpose of this study was to examine the effects of inspiratory muscle training
      (IMT) on ventilatory muscle strength and dyspnea in patients with chronic HF.
      SUBJECTS: Fourteen patients (mean age [+/-SD] = 52 +/- 8.5 years) with end-stage
      cardiomyopathy and chronic HF (mean left ventricular ejection fraction = 23% +/-
      13% and New York Heart Association class = 3.6 +/- 0.6) participated in the
      study. METHODS: Inspiratory muscle training was performed at 20% of maximal
      inspiratory pressure (MIP) for 5 to 15 minutes, three times a day, for 8 weeks.
      Dyspnea was evaluated at rest and during exercise. RESULTS: Both MIP and maximal
      expiratory pressure (MEP) were greater after 2 weeks of IMT (51 +/- 21 to 63 +/-
      23 cm H2O and 85 +/- 22 to 96 +/- 19 cm H2O, representing 24% and 13%
      improvement). Dyspnea scores at rest and during exercise decreased after 2 weeks
      (2.0 +/- 0.7 to 1.3 +/- 0.5 and 3.6 +/- 0.5 to 2.6 +/- 0.6, representing 29% and
      28% improvement) and plateaued throughout the remainder of IMT. Baseline MEP was
      related to the percentage of change in MEP after IMT (r = -.72), and several
      measures of pulmonary function were related to the degree of improvement in
      dyspnea after IMT (r = -.57 to -.82) and in MIP after IMT (r = .71). CONCLUSION
      AND DISCUSSION: Improvements in MIP, MEP, and dyspnea were found after 2 weeks of
      IMT. Greater pulmonary function was associated with greater improvement in
      dyspnea and ventilatory muscle strength after IMT. These improvements may
      decrease the dependency and impairment associated with chronic HF.

PMID- 9256870
TI  - The Patient-Specific Functional Scale: measurement properties in patients with
      knee dysfunction.
AB  - BACKGROUND AND PURPOSE: Assessing disability is important, and numerous
      interviewer-assisted and self-report questionnaires are used to accomplish this
      task. These questionnaires can be classified as being generic, condition or
      disease specific, or patient specific. The purpose of this study was to determine
      test-retest reliability, construct validity, and sensitivity to change of the
      Patient-Specific Functional Scale (PSFS) when applied to patients with knee
      dysfunction. SUBJECTS: Subjects were 38 physician-referred patients with knee
      dysfunction. METHODS: The PSFS and the Medical Outcomes Study 36-Item Short-Form
      Health Survey were administered at a patient's initial visit and following 2 to 3
      weeks of treatment. An assessment of global change was also made by the patient
      and clinician at follow-up. These measures allowed the assessment of construct
      validity and sensitivity to change. To obtain an estimate of reliability, the
      PSFS was also administered within 72 hours of the initial assessment. RESULTS:
      Test-retest reliability and sensitivity to change were excellent (intraclass
      correlation coefficient [type 2,1] R = .84 and Pearson's r = .78, respectively).
      Validity was also confirmed. CONCLUSION AND DISCUSSION: Previous investigation on
      persons with low back pain suggested that the PSFS has promising measurement
      properties. The results of this study provide further evidence supporting the
      reliability, validity, and efficiency of the PSFS. Further investigation is
      needed to determine the extent to which the PSFS can be applied across a variety
      of conditions and age groups.

PMID- 9256872
TI  - The suppressive effect of electrical stimulation on nociceptive responses in the
      rat.
AB  - BACKGROUND AND PURPOSE: The aim of this investigation was to study the effect of
      electrical stimulation on nociceptive responses within the lumbar levels of the
      rat spinal cord. METHODS: A single high-energy thermal pulse produced by a
      surgical laser stimulator (5 W, 30 milliseconds) was applied on the plantar
      surface of the hind paws of male Sprague-Dawley rats. The spinal cord field
      potential evoked by the laser pulse was used as an indicator of thermosensitive
      nociceptive responses. Low-intensity single stimulation, high-intensity single
      stimulation, low-intensity train stimulation, and high-intensity train
      stimulation were applied on the common peroneal nerve with protected cuff
      electrodes in different trials. RESULTS: Neither low-intensity nor high-intensity
      single stimulation suppressed field potentials. In contrast, low-intensity train
      stimulation elicited partial inhibition of field potentials. Furthermore, high
      intensity train stimulation elicited biphasic inhibition at a wider range of
      intervals lasting for 20 seconds. CONCLUSION AND DISCUSSION: The results
      demonstrate that two modes of train electrical stimulation can produce two
      patterns of fast-onset (within milliseconds), short-duration (within 20 seconds)
      inhibition of field potentials in the spinal cord. These results provide evidence
      that noxious heat-related impulses are modulated by the presence of specific
      electrical stimulation. The clinical application of transcutaneous electrical
      nerve stimulation to block pain is supported.

PMID- 9256873
TI  - The individualized treatment of a patient with benign paroxysmal positional
      vertigo.
AB  - The purpose of this case report is to describe the evaluation and treatment of a
      patient with vertigo. The patient was a 32-year-old male carpenter with a 17-year
      history of episodic vertigo that occurred when his neck was in the extended
      position while positioned supine and during walking. His medical and physical
      therapy evaluative findings were consistent with a diagnosis of benign paroxysmal
      positional vertigo (BPPV). He was treated with an individualized home exercise
      program of eye movement exercises, Brandt/Daroff exercises, and general
      conditioning exercises. Twenty-four days from the start of physical therapy, the
      patient was free of symptoms even when his neck was in the extended position.

PMID- 9256874
TI  - Legislative alert.

PMID- 9256875
TI  - Expectant fathers: influence of perinatal education on stress, coping, and
      spousal relations.
AB  - The purpose of this quasi-experimental study was to compare the effects of father
      focused discussion perinatal classes with traditional childbirth classes on
      expectant fathers' stress/psychological symptom status, coping strategies, social
      support, and spousal relations (both supportive behavior toward their partners
      and couple-conflict behavior). Relative to fathers in traditional childbirth
      classes, those in father-focused discussion classes significantly increased their
      use of reasoning during conflicts and their housework activity. Both groups of
      fathers reported a significant increase in social network support and an increase
      in baby/pregnancy-related activity. Neither group substantially increased their
      overall coping responses, although men in the father-focused group significantly
      changed their coping efforts by seeking more social support, particularly getting
      information and emotional support from their partner's physician. Implications
      for perinatal education practice are discussed, and suggestions for future
      research are offered.

PMID- 9256876
TI  - HOME inventory and NCATS: relation to mother and child behaviors during
      naturalistic observations. Home Observation for Measurement of the Environment.
      Nursing Child Assessment Teaching Scale.
AB  - The purpose of this study was to determine the relationships among the Nursing
      Child Assessment Teaching Scale (NCATS), the Home Observation for Measurement of
      the Environment (HOME) inventory, and interactive behaviors observed in the home
      for fifty-three 3-year-old, prematurely born children and their mothers. The
      total HOME score showed high internal consistency, with moderate subscale levels.
      NCATS total score showed high internal consistency, but low to moderate subscale
      consistency. Combining NCATS subscales into a mother subscale and child subscale
      improved internal consistency. The HOME and the NCATS mother subscale correlated
      with observed maternal behaviors, but the NCATS child subscale was unrelated to
      child behaviors. Relationships between observed behaviors and HOME scores did not
      differ for high- and low-education mothers or for Caucasians and African
      Americans, but only low-education mothers and African Americans exhibited
      correlations between NCATS scores and observed behaviors. These results show the
      HOME, NCATS, and naturalistic observations measure related, but not overlapping,
      aspects of the mother's contribution to her relationship with her child, but the
      NCATS child subscale should be used with caution with 3-year-olds.

PMID- 9256877
TI  - Predictors of the development of chronic pain.
AB  - The purpose of this secondary analysis was to explore the role of potential risk
      factors in predicting the development of chronic pain. Linear discriminant
      function analysis was used to derive a prediction equation that maximized the
      differences between a group of hospitalized patients experiencing acute pain who
      developed chronic pain (n = 171) and a group whose pain resolved (n = 200).
      Patients who developed chronic pain reported a higher pain intensity, higher
      anxiety and distress, less certainty that their pain would resolve, longer
      hospitalization, less independence in ambulation, a diagnosis of trauma, and less
      need for surgery. Recognition of these factors could lead to early identification
      of those individuals with acute pain who are at risk for developing chronic pain.

PMID- 9256878
TI  - Social support sources among older women with heart failure: continuity versus
      loss over time.
AB  - The extent to which older women with heart failure experienced continuity or loss
      of their support sources and the relationship between support source loss,
      perceived enacted support, and psychological well-being were examined in this
      study. In-home interviews were conducted with 57 older women who completed two
      interview 18 months apart following a hospital admission for heart failure. Both
      the emotional and tangible support sources were quite stable, indicating that the
      predominant pattern is continuity for older women with heart failure. Loss of
      tangible support sources was related to a perception of receiving less tangible
      support and less positive affect. Implications for future research and nursing
      practice are discussed.

PMID- 9256879
TI  - PMS after 40: persistence of a stress-related symptom pattern.
AB  - The purpose of this study was to compare women over 40 years of age with
      premenstrual syndrome (PMS) to women with a low-severity (LS) symptom pattern
      with respect to physiologic indicators of stress arousal and response, stress
      hormone arousal, stressful life circumstances, anger, self- and social control,
      and interpersonal sensitivity. Women with PMS experienced more negative life
      events, more difficulty with anger, and more concerns about self- and social
      control, than women with an LS pattern. These experiences were coupled with
      increased physiologic arousal and stress responses (skin conductance and muscle
      tension levels) and relatively higher norepinephrine levels than for women with
      an LS pattern, but with dampened cardiovascular responses to stressors. As they
      age, women with a PMS symptom pattern demonstrate persistent differences in
      stress arousal and response from women with an LS pattern.

PMID- 9256880
TI  - Empowerment and staff nurse decision involvement in nursing work environments:
      testing Kanter's theory of structural power in organizations.
AB  - Work redesign initiatives have transformed approaches to patient care that will
      require increased control of nurses over both the content and context of their
      practice. A secondary analysis of two studies linking perceived work empowerment
      with two aspects of staff nurse decisional involvement using Kanter's (1977,
      1993) theory of structural power in organizations is described. In these studies,
      the pattern of relationships among variables in Kanter's theory and two different
      facets of work decisional involvement (control over the content and context of
      nursing practice) were examined using structural equation modeling techniques.
      Consistent with theoretical expectations, perceptions of formal and informal
      power significantly influenced perceived access to work empowerment structures.
      Informal power was found to mediate the relationship between formal power and
      access to work empowerment structures. Formal and informal power and access to
      empowerment structures, in combination, were found to be significant predictors
      of the extent of involvement in decisions related to the content and context of
      nursing practice, respectively. The results provide empirical support for
      propositions derived from Kanter's theory of work empowerment, and provide
      potential guidance for theory-based management practices to enhance nurses'
      involvement in professional and organizational decision making.

PMID- 9256881
TI  - Line of reasoning as a representation of nurses' clinical decision making.
AB  - Line of reasoning (LOR) is offered as an alternative representation of clinical
      decision making for studies using protocol analysis. A LOR is defined as an
      argument or set of arguments leading to a conclusion. Because LOR combines both
      knowledge and cognitive processes, it provides a more complete representation of
      how a person uses knowledge to make a decision in a particular situation than do
      other representations. Operationalization of LOR in the form of templates and
      narratives enhances systematic data interpretation and coding. The use of LOR as
      a representation is illustrated in a study of critical care nurses' clinical
      decision making, specifically the determination of a patient's readiness to wean
      from mechanical ventilation.

PMID- 9256882
TI  - Focus on qualitative methods. Qualitative metasynthesis: issues and techniques.
AB  - There has been an accumulation of qualitative studies in recent years, but little
      cumulation of the understandings gained from them. Qualitative research appears
      endangered both by efforts to synthesize studies and by the failure to do so.
      Techniques used have included reciprocal translations of key metaphors and
      concepts and qualitative and quantitative comparative analyses to produce
      narrative and theoretical integrations. The major problem yet to be resolved is
      developing usable and communicable systematic approaches to conducting
      metasynthesis projects that maintain the integrity of individual studies.

PMID- 9256883
TI  - Continuous-infusion 5-fluorouracil and cisplatin for advanced/recurrent
      transitional cell cancer of the bladder: a Southwest Oncology Group trial.
AB  - Significant toxicities result from the use of MVAC (methotrexate, vinblastine,
      adriamycin, cisplatin) for advanced/ recurrent transitional cell carcinoma of the
      bladder (ARTCCB). An alternative regimen of 5-fluorouracil (5-FU) and cisplatin
      was evaluated by Southwest Oncology Group (SWOG). Thirty-eight patients with
      ARTCCB were treated with continuous infusion 5-FU 1,000 mg/m2/days 1-5 and
      cisplatin 100 mg/day 1, on a every-21-days schedule. There were two complete
      responses (CR) and eight partial responses (PR) among 36 eligible patients, for
      an overall response rate of 28% [95% confidence interval (CI) 14-45%]. Median
      duration of response was 6 months, and median duration of survival was 9 months.
      No toxic deaths occurred. Grade 4 leukopenia occurred in 5 patients. Other
      toxicities were mild. Only two documented infections occurred in 5 patients with
      neutropenia. The response rate of 28% is better than that achieved with cisplatin
      alone and not dissimilar to the range of response for MVAC. Toxicities were less
      and tolerable. This regimen will need further evaluation.

PMID- 9256884
TI  - Continuous infusion, intravesical doxorubicin for the treatment of regionally
      advanced bladder cancer: a phase I-II trial.
AB  - Patients with regionally advanced bladder cancer not considered candidates for
      definitive surgical intervention underwent continuous antegrade infusion of
      doxorubicin by percutaneous nephrostomy tube. Doxorubicin was administered for 7
      consecutive days at a rate designed to achieve target urinary concentrations
      (range 5-80 micrograms/ml). Urine and serum concentrations of doxorubicin were
      monitored daily. Toxicity was assessed by serial renal scans, antegrade
      nephrostograms, blood counts, and serum chemistries. Patients were restaged after
      three cycles of therapy. In all, 23 cycles, constituting 156 days of therapy,
      were administered to 10 patients. Target urinary drug levels were achieved during
      all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No systemic
      (neutropenia or myocardial dysfunction) or regional toxicity (extravasation,
      sepsis, stricture) was noted. Five of 10 patients tolerated the planned three
      treatment cycles. Poor performance status (PS, Eastern Cooperative Oncology
      Group: ECOG 3) strongly correlated with treatment intolerance and early death
      from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable
      disease, I had radiographic partial response (PR) with a biopsy demonstrating
      extensive tumor necrosis, I had no identifiable tumor at the time of restaging
      transurethral resection of bladder tumor (TURBT), and a final patient with upper
      and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no
      evidence of disease). These findings demonstrate the feasibility and low toxicity
      of this approach.

PMID- 9256885
TI  - Cellulitis of the breast as a complication of breast-conserving surgery and
      irradiation.
AB  - Breast-conserving therapy (BCT) has become a standard treatment option for
      patients with early-stage breast cancer. We have observed cellulitis of the
      treated breast as a complication occurring before, during, and after breast
      irradiation. The cases of five women (median follow-up, 28 months; range, 24-65
      months) who developed cellulitis before (n = 1), during (n = 2), or after (n = 2)
      breast irradiation were reviewed. A consecutive series of BCT patients at Emory
      University was reviewed to determine the incidence of this complication. Four of
      five women had an axillary dissection, yielding a median of 14 negative lymph
      nodes (range, 6-22 nodes). Two of four patients developed axillary seromas
      requiring aspiration. In these four patients, only the breast was irradiated. A
      fifth patient had no axillary dissection and had breast and
      supraclavicular/axillary irradiation. The median whole breast dose was 50 Gy
      (range, 46-50.4 Gy). The clinical features of cellulitis included erythema,
      edema, tenderness, and warmth in all patients. Cellulitis was a relapsing problem
      for four of the five patients. The incidence of this complication in our series
      of BCT patients was approximately 1%. Cellulitis in the ipsilateral breast can be
      a relapsing complication of BCT and can be seen before, during, or after breast
      irradiation. Axillary seromas and aspiration seem to indicate a subset of
      patients at risk of early cellulitis. Late cellulitis may be caused by a variety
      of factors related to modifications of vascular and skin integrity by surgery and
      radiotherapy. Prompt diagnosis and appropriate antibiotic therapy is recommended.
      This problem need not interrupt a course of breast irradiation, and does not
      necessarily lead to a poor cosmetic result.

PMID- 9256886
TI  - Phase I-II study of combined 5-fluorouracil and cisplatin chemotherapy and
      altered fractionation radiotherapy for advanced squamous cell carcinoma of the
      cervix.
AB  - Forty patients with advanced carcinoma of the cervix were prospectively treated
      by an intermodality approach using chemotherapy combination concomitant with
      split-course hyperfractionated radiation therapy (RT). Cisplatin (CDDP) (60
      mg/m2) was administered before radiotherapy initiation followed by 5-fluorouracil
      (5-FU) (750 mg/m2) for 5 days during the first week of irradiation. The same
      schedule was repeated in the last week of the RT, with 5-FU administration (1,000
      mg/m2) for only 3 days. RT consisted of 5,020 cGy to the pelvis, followed by two
      intracavitary applications for a total of 5,000-5,500 mg/h radium equivalent when
      possible: 140 cGy/fraction was administered in the morning and evening, with a 6
      h interval. The remainder of the external beam radiation was delivered at a
      standard daily fractionation of 180 cGy/fraction to a total dose of 5,020 cGy.
      This regimen of RT with concomitant chemotherapy had minimal toxicity and did not
      cause significant prolongation of the treatment program. However, a high rate of
      late complications was noted in patients who had extended-field RT due to
      paraaortic lymph node involvement. Thirty-two patients had complete response (CR)
      (80%). 24 (75%) of whom have no evidence disease (NED), with a median follow-up
      of 24 months. Our study suggests that this regimen of combined chemotherapy and
      RT in this group of patients with poor prognosis is effective and well tolerated,
      with acceptable acute toxicity and late morbidity.

PMID- 9256887
TI  - CEA, CA 19-9, and CA-50 in monitoring gastric carcinoma.
AB  - This study was conducted to investigate the clinical utility of CEA, CA 19-9, and
      CA-50 in the diagnosis, monitoring, and prognosis of 62 gastric carcinoma
      patients having either adjuvant or palliative chemotherapy. Patients were divided
      in two groups: group A included patients treated on an adjuvant basis following a
      curative resection of gastric cancer, and group B included patients with residual
      disease post surgery or patients with inoperable tumor or generalized disease.
      Serum marker levels were measured in a prospective study just before the
      initiation of chemotherapy and before each course during chemotherapy. In group
      A, CEA was positive in 2/25 (8%) patients, CA 19-9 in 1/25 (4%), and CA-50 in
      1/25 (4%). In group B the sensitivity of CEA was 48.6% (18/37 patients), of CA 19
      9 64.9% (27/37 patients), and of CA-50 70.3% (26/37) patients. There was a
      significant correlation between the CA 19-9 and CA-50 levels in both groups. No
      correlation was found between the sensitivity or the absolute initial marker
      levels and the tumor's differentiation or extent of disease. In group A the only
      patient with initially elevated CA 19-9 and CA-50 values relapsed early while he
      was on adjuvant chemotherapy. It was also found that the rising final CA 19-9 and
      CA-50 values at the end of chemotherapy were correlated with an increased
      incidence of relapse, but not with the disease-free interval. In group B the
      initially low marker levels showed a trend to predict a favorable outcome of
      treatment. There was no statistically significant correlation between the marker
      titers before each course and response to chemotherapy. It is concluded that the
      comeasurement of CA 19-9 and CA-50, and to some degree of CEA, is justifiable for
      gastric cancer. The estimation of CA 19-9 and CA-50 may be useful for early
      detection of recurrence after curative surgery and adjuvant chemotherapy. In
      advanced or recurrent gastric cancer, the estimation of either CA 19-9 or CA-50
      and CEA serum values may help in checking the prognosis, determining the efficacy
      of palliative treatment modalities, and recognizing recurrences.

PMID- 9256889
TI  - Results of re-irradiation of primary intracranial neoplasms with three
      dimensional conformal therapy.
AB  - We evaluated the potential of three-dimensional conformal therapy for re
      irradiation of selected intracranial neoplasms and reviewed the retreatment of 20
      patients at the University of Michigan between May 1988 and August 1991. All
      patients had previously undergone a full course of external beam radiotherapy
      (RT) to a median dose of 5,940 cGy (range 5,100-6,500 cGy), including five whole
      brain treatments. All recurrences were unsuitable for brachytherapy or
      radiosurgery. Various histologies were retreated, including 14 high-grade
      gliomas. Median time to re-irradiation was 38 months (range 9 months to 19 years,
      6 months). RT was delivered with complex plans designed using fully integrated
      computed tomography/magnetic resonance imaging (CT/ MRI) tumor volume
      information, and regions of previous parenchymal treatment were avoided if
      possible. Composite (initial+retreatment) dose-volume histograms (DVH) of dose to
      nontarget brain allowed comparison of alternative plans to select beam
      orientations which minimized normal brain irradiation. Mean target dose of re
      irradiation was 3,600 cGy (range 3,060-5,940 cGy). Total cumulative dose ranged
      from 8,060 to 11,940 cGy. Median survival was 9 months, and 1-year actuarial
      survival was 26%. After retreatment, 8 of 12 patients (67%) had steroid dose
      decrement and neurologic improvement at 4-48 months (median duration 14 months).
      Radiographic regression or stabilization of disease was noted in 11 of 16
      patients (68%). Re-irradiation with highly conformal three-dimensional planning
      provides frequent clinical improvement with acceptable morbidity and should be
      considered in selected patients with recurrent intracranial neoplasms.

PMID- 9256888
TI  - Gonadal function following ABVD therapy for Hodgkin's disease.
AB  - To assess the effect of combination chemotherapy with doxorubicin, bleomycin,
      viablastine, and decarbazine (ABVD) on gonadal function in patients treated for
      Hodgkin's disease, we assessed 38 male patients with Hodgkin's disease who were >
      15 years of age and in complete remission for the development of secondary sexual
      characteristics, sexual habits, and fatherhood after treatment. Semen analysis
      and serum hormone level estimation of follicle-stimulating hormone (FSH),
      leutinising hormone (LH), and testosterone (T) were done in all cases. Twenty-six
      patients received ABVD therapy and 12 received a combination of ABVD with COPP or
      MOPP (cyclophosphamide or nitrogen mustard, vincristine, procarbazine, and
      prednisone). Radiation of the pelvic region was done in one case. Median time
      between completion of therapy and assessment of gonadal function was 34 months
      (range, 12-68 months). Secondary sexual characteristics developed normally in all
      patients. Azoospermia was seen in one patient from the ABVD group and 10 patients
      from the COPP/ABVD group (p < 0.001). Serum FSH levels were significantly higher
      in the COPP/ABVD group than in the ABVD group (23.5 versus 4.7 mlu/ml; p < 0.001)
      The levels were in the normal range in 23 patients from the ABVD group, as
      compared to four in the COPP/ABVD group (88.5% versus 33.3%; p < 0.001). Three
      patients treated with ABVD fathered children post-therapy. We conclude that ABVD
      is associated with relatively better preservation of gonadal function.

PMID- 9256890
TI  - Phase II trial with BCNU plus alpha-interferon in patients with recurrent high
      grade gliomas.
AB  - A Phase II study with a combination of BCNU and alpha-interferon (IFN) was
      conducted in patients with high-grade glioma recurrent after surgery and
      radiation treatment in order to investigate tumor control and toxicity. Twenty
      one non-chemotherapy pretreated patients were administered 6 MU alpha-IFN in a 2
      h infusion followed by 150 mg/m2 BCNU i.v. on day 1. Three MU alpha-IFN were
      subsequently administered subcutaneously on alternating days three times a week,
      until recycling of the whole procedure on day 42. Among 21 patients, partial
      remission was obtained in 7 (33%; 95% CI = 15-57) and stable disease in 6 (29%;
      CI = 11-52); overall Kaplan-Meier median time to progression (TTP) was 4.5 months
      (CI = 4-9) and the overall median survival time (MST) was 7 months (CI = 5-13).
      In patients who underwent surgical redebulking prior to chemotherapy, TTP and MST
      were 9 (CI = 7-14) and 15 months (CI = 11.0-39.0); in patients who were not
      operated on again before chemotherapy, these values were 4 (CI = 2-5; log rank
      test, p = 0.0026) and 5.5 months (CI = 4-7; log rank test, p = 0.0012)
      respectively. The results of this regimen in relapsing patients, especially
      following surgical redebulking, are encouraging; toxicity is acceptable, and
      further studies on combined alpha-IFN and multiple-agent chemotherapy are
      warranted.

PMID- 9256891
TI  - Phase II evaluation of cisplatin and WR2721 for refractory metastatic breast
      cancer.
AB  - Cisplatin, as second-line therapy for metastatic breast cancer (MBC), has at best
      shown only modest response rates. At high doses, the toxicity profile of this
      drug may outweigh any potential benefits for MBC patients. We performed a phase
      II study to determine whether the investigational agent WR2721 would mitigate the
      toxicity of cisplatin in patients with MBC and to assess the antitumor response
      of cisplatin as salvage therapy. Thirteen women were enrolled in the study.
      Cisplatin was administered at a dose of 120 mg/m2 together with WR2721 at a dose
      of 910 mg/m2 intravenously every 21 days. Response was assessed at the end of two
      cycles, and toxicity was evaluated after each treatment cycle. No objective
      antitumor responses were noted. Three patients exhibited toxicity from cisplatin
      in the form of ototoxicity, nephrotoxicity, myelotoxicity, and persistent delayed
      nausea and vomiting necessitating discontinuation from the study. There was one
      death from renal failure. WR2721 itself caused significant but transient
      hypotension in 46% of the patients. In our experience, salvage chemotherapy with
      cisplatin in pretreated patients with MBC produced no objective responses. WR2721
      did not prevent the occurrence of organ toxicity.

PMID- 9256892
TI  - Case report of anaphylaxis from cisplatin/paclitaxel and a review of their
      hypersensitivity reaction profiles.
AB  - Anaphylaxis is one of the most catastrophic, although infrequent, potential side
      effects of chemotherapy. We report the case of a patient who developed
      respiratory distress and who could not be resuscitated after his sixth cycle of
      cisplatin and paclitaxel for squamous carcinoma of the lung and false vocal cord.
      Autopsy confirmed anaphylaxis as the cause of death. The major hypersensitivity
      profiles of these two agents, as described in case reports and in the medical
      literature, were reviewed to determine which of the two therapies was the
      underlying cause of the patient's reaction. Anaphylaxis has been reported with
      both cisplatin and paclitaxel. Cisplatin is argued to be the most likely etiology
      for anaphylaxis in this case.

PMID- 9256893
TI  - Small cell anaplastic carcinoma of the prostate: seven new cases, review of the
      literature, and discussion of a therapeutic strategy.
AB  - Small cell anaplastic carcinoma of the prostate (SCCP) is a rare entity; a
      literature review disclosed fewer than 150 cases. SCCP has an aggressive course,
      and both local and distant failure is common. The optimal treatment method has
      not been clearly established. We review our experience with 7 patients, with
      attention paid to clinical and pathological details based on a review of the
      histological specimens. Three patients had mixed tumors of both SCCP and
      adenocarcinoma, 3 had pure adenocarcinomas that recurred as small cell, and 1 had
      pure small cell. Our series confirms the aggressive nature of the disease, with
      all patients dying of their disease < or = 42 months after diagnosis. All
      patients progressed locally, and at least 5 later developed distant metastases.
      Treatment with combination chemotherapy and/or hormones resulted in short-lived
      responses in most patients. We recommend use of hormonal manipulation and
      combination chemotherapy as well as surgery and/or radiation therapy to the
      prostate for local control and emphasize that histologic recognition of the
      entity is important for proper treatment.

PMID- 9256894
TI  - Mitoxantrone in the treatment of metastatic transitional cell carcinoma of the
      prostate. A case report.
AB  - A 61-year-old man with pulmonary and bone metastases from a primary transitional
      cell carcinoma of the prostate (TCCP) refractory to MVAC was treated with
      mitoxantrone 16 mg/m2 i.v. at 3-week intervals. With this, he experienced an
      objective partial remission lasting 5 months and a significant decrease in cancer
      related symptoms. Mitoxantrone deserves further evaluation in this rare disease.

PMID- 9256895
TI  - Phase II study of estramustine, oral etoposide, and vinorelbine in hormone
      refractory prostate cancer.
AB  - Hormone-refractory prostate cancer is characterized by a low response rate
      following second-line therapy. Encouraging results have been reported in Phase II
      studies with estramustine associated with vinblastine or etoposide. Vinorelbine
      is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate
      cancer. We therefore evaluated the activity of the following schedule:
      estramustine, 400 mg/m2 orally days 1-42; etoposide, 50 mg/m2 orally days 1-14;
      and 28-42; vinorelbine, 20 mg/m2 days 1, 8, 28, and 35; cycles being repeated
      every 8 weeks. Twenty-five patients have been included and are assessable for
      response and side effects. Patient characteristics were as follows: median age,
      71 years (range 55-81); ECOG performance status 0-2; nonosseous disease, 3 cases;
      bone metastases, 23 cases. Sixty-two cycles have been delivered. Two patients
      with measurable disease and six patients with bone disease had a partial
      remission for an overall response rate of 32% (95% confidence interval 15-53%).
      Seven patients had stabilization of disease and 10 had progression of disease.
      Median duration of response was 3 months (range 2-5). Prostate-specific antigen
      in 14 patients (56%) decreased from baseline by at least 50%. Toxicity was
      manageable. Neutropenia was mild, with only three cases of grade III-IV toxicity.
      Two patients had severe anemia. The results of this study indicate that the
      schedule is active and well tolerated in hormone-refractory prostate cancer
      patients.

PMID- 9256896
TI  - Retrospective comparative analysis of 5FU + low-dose folinic acid vs. 5FU + high
      dose folinic acid in the treatment of metastatic colorectal cancer. The Ottawa
      experience.
AB  - Two regimens of 5FU and folinic acid in the treatment of metastatic colorectal
      cancer were retrospectively analyzed. 33 patients received the high dose (HD)
      schedule (5FU 370 mg/m2 and Folinic Acid 200 mg/m2 i.v. on D1-5, every 4 weeks),
      61 patients received the low dose (LD) schedule (5FU 400 mg/m2 and Folinic Acid
      20 mg/m2 i.v. on D1-5, every 4 weeks). One patient in each group achieved a
      complete response, the overall response rate was 28% and 11% for the HD and LD
      groups, respectively. The median response duration was 183 days for the HD and
      112 days for the LD group. The median survival duration was 387 days for the HD
      and 405 days for the LD group. The response rate and duration of response were
      higher in the HD group though this did not reach statistical significance. There
      was no difference in overall survival between the two patient groups. Neutropenia
      and gastro-intestinal symptoms were the most common toxicities, they were equal
      in both groups. One patient (3%) in the HD and 5 patients (9%) in LD group
      discontinued treatment due to toxicity. There were no treatment related deaths.
      It is concluded that low dose folinic acid in combination with 5FU is effective
      and produces similar toxicities as high dose folinic acid. It is concluded that
      low dose folinic acid in combination with 5FU is an effective alternative to high
      dose regimen in the palliative management of patients with metastatic colorectal
      cancer. However though it did not reach statistical significance the high dose
      regimen was associated with a higher response rate. This could have a significant
      effect when the combination is used in the adjuvant treatment of high risk
      patients.

PMID- 9256897
TI  - Phase II trial of dose intensification with cisplatin and carboplatin plus
      vindesine in patients with inoperable non-small cell lung cancer.
AB  - We conducted a phase II trial of a regimen that combined cisplatin (CDDP),
      carboplatin (CBDCA), and vindesine (VDS) in previously untreated patients with
      non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of the
      regimen. Thirty-five patients with inoperable NSCLC entered the study. Cisplatin
      (CDDP 80 mg/m2) was administered on day 1, and CBDCA 100 mg/m2 and VDS 2 mg/m2)
      were administered on days 2, 3, and 8. We observed one complete response (CR) and
      16 partial responses (PR), with a total response rate of 49% [95% confidence
      interval (CI) 31-66%]. The overall median survival was 58 weeks; the 1-year
      survival rate was 60%, and the 2-year survival rate was 23%. Major toxicities
      were hematologic; leukopenia of grades 3 and 4 occurred in 66% patients, and
      thrombocytopenia occurred in 23%. Therefore, the dose-intensified regimen of
      CDDP, CBDCA, and VDS was active in treating patients with inoperable NSCLC, with
      demonstration of a favorable median survival time.

PMID- 9256898
TI  - Multidrug-resistant gene expression in small-cell lung cancer.
AB  - The development of drug resistance can contribute to treatment failure in small
      cell lung cancer (SCLC). In this report, we investigate p-glycoprotein-mediated
      multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to
      treatment and at relapse if possible, short-term culture was carried out, and
      these tumor cells were analyzed for MDR gene expression by slot blot and reverse
      transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis.
      Three cell lines were also established from short-term cultures. Twenty-four
      patients with MDR(-) and seven with MDR +(++) were available for survival
      analysis. Median survival for MDR (-) patients was 10 months, whereas for MDR
      +(++) patients it was 2 months. This was statistically significance (p < 0.0007).
      The presence of MDR1 gene expression also correlated with the lack of response to
      chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in
      patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1
      gene expression can occur in intrinsically MDR(+) SCLC cells after multiple
      passages in drug-free media. We concluded that increased MDR1 gene expression is
      present in a small number of SCLC both before and after chemotherapy and usually
      signifies poor survival and no response to chemotherapy.

PMID- 9256899
TI  - Cisplatin and vinorelbine followed by radiotherapy in the treatment of stage III
      B non-small-cell lung cancer patients.
AB  - Combined chemotherapy/radiotherapy treatments appear to yield better results in
      locally advanced non-small-cell lung cancer (NSCLC) than radiotherapy alone. The
      optimal induction chemotherapy regimen remains to be established. In the present
      study, chemotherapy with cisplatin and vinorelbine was used prior to radical
      radiotherapy in Stage III-B NSCLC. Thirty-three patients were entered
      prospectively into a Phase II study. Treatment consisted of three cycles of
      chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1
      and 8, followed by thoracic radiotherapy (60 Gy). Twenty-two percent of the 33
      patients had grade 3-4 leukopenia, and there were six episodes (in 4 patients) of
      neutropenia-associated fever. Gastrointestinal toxicity was generally moderate.
      Peripheral neuropathy was present in 42% of the patients, although in most of
      them it was slight. The main radiotherapy toxicity was esophagitis grade I-II.
      Evaluation of response after the third chemotherapy course showed an objective
      response in 16 patients (48%), whereas in three patients (9%) the disease
      progressed during therapy. The median survival of the entire group was 13 months.
      Cisplatin plus vinorelbine followed by radiotherapy is an effective schedule for
      patients with locally advanced non-small-cell lung cancer.

PMID- 9256901
TI  - Mediastinal epithelioid hemangioendothelioma in a patient with type IV Ehlers
      Danlos syndrome: a case report and review of the literature.
AB  - Ehlers-Danlos syndrome (EDS) is a collection of inherited connective tissue
      disorders with at least 10 types, differentiated on clinical and genetic grounds.
      Malignancy has been described only rarely in association with the syndrome.
      Epithelioid hemangioendothelioma (EH) is a rare endothelial tumor, which displays
      clinical behavior intermediate between that of hemangioma and angiosarcoma. A
      case report of a 50-year-old man with type IV EDS who was extensively
      investigated for several years for multiple mediastinal nerve palsies and chest
      pain. Magnetic resonance imaging (MRI) demonstrated an anterior mediastinal mass,
      which at biopsy showed EH. Subsequent metastatic spread to liver and lungs is
      unique among reported cases of mediastinal EH. The patient experienced
      significant symptomatic improvement from external beam radiotherapy (RT) to the
      mediastinum. After metastatic disease developed, multiagent chemotherapy was
      administered, but without response. The literature is reviewed regarding
      treatment of EH and the potential problems associated with EDS. Although there
      appears to be no etiological association between EDS and EH, the connective
      tissue disease clearly contributed to a delay in diagnosis and raised concerns
      regarding RT tolerance. The potential predisposition to aggressive tumor invasion
      remains a possibility. In addition, mediastinal EH has the potential to
      metastasize, and in this case demonstrated resistance to a broad range of
      chemotherapy agents.

PMID- 9256900
TI  - Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral
      mucositis?
AB  - Therapeutic application of immunoglobulin is reported to be successful in
      radiation-induced oral and oropharyngeal mucositis. In this study the efficacy of
      prophylactic application of immunoglobulin was investigated. In 42 patients with
      head and neck cancer, postoperative radiation treatment or radiation combined
      with chemotherapy was performed. In 20 consecutive patients, prophylactic
      mucositis treatment consisted of panthenol (4 x 10 ml/day) and nystatin (4 x 1
      ml/day). The 22 following patients received, supplementary to panthenol and
      nystatin, 800 mg (5 ml) human immunoglobulin intramuscularly once weekly. During
      the treatment time, the degree of mucositis was examined 3 times a week. The
      distribution of maximal mucositis degree revealed slightly more severe mucous
      membrane reaction in the control group compared with the immunoglobulin group
      (n.s.). The analysis of mean mucositis degrees in both groups demonstrated
      statistically significant differences (t test, p = 0.031) related to the entire
      group (n = 42) and to those 16 patients receiving radiation combined with
      chemotherapy. There was no significant immunoglobulin-induced effect on mucositis
      in patients treated by radiation alone. The time from the beginning of therapy to
      the first interruption could be prolonged 5 days in the immunoglobulin group
      (n.s.). In conclusion, it is demonstrated that the prophylactic application of
      immunoglobulin seems to lower the degree of radiation-induced mucositis. In
      comparison to the published data about therapeutically given immunoglobulin, the
      clinical efficacy of the prophylactic application of immunoglobulin as it is
      performed in this study is less evident.

PMID- 9256902
TI  - Spontaneous regression of metastatic renal cancer. Case report and literature
      review.
AB  - A case of spontaneous regression of pleural and intrapulmonary metastases from
      renal cell cancer is reported with more than 60 cases reported since the original
      review of this clinical phenomenon in 1964. The metastatic disease sites are most
      often pulmonary, but extrapulmonary sites include liver, bone, and CNS
      regressions. The role of nephrectomy in "spontaneous regression" continues to be
      obscure, accounting for < 50% of documented cases. Immunologic mechanisms,
      although intellectually attractive, have not been identified.

PMID- 9256903
TI  - Should soybean agglutinin purging be performed in breast cancer patients
      undergoing autologous stem cell transplantation? A retrospective analysis of 48
      patients.
AB  - High-dose chemotherapy (HDC) followed by autologous stem cell transplantation
      (ASCT) has gained an increasing role in the treatment of high-risk Stage II-III
      and/or metastatic breast cancer patients. Several investigators reported on a
      high rate of tumor cells contaminating the bone marrow and peripheral blood stem
      cell collection. Nevertheless, the clinical implication of reinfusion of tumor
      cells with the stem cells to the relapse rate is still uncertain. In this
      retrospective analysis we compare the outcome and the toxicity of 29 patients
      with high-risk Stage II-III and 19 metastatic breast cancer patients who
      underwent HDC with ASCT. Thirteen patients underwent transplant with soybean
      agglutinin (SBA)-purged graft, while 35 consecutive patients received
      unmanipulated graft. Engraftment was significantly faster for the nonpurged
      transplant. No differences in disease-free survival, freedom from relapse, or
      overall survival were noted in both groups during a median follow up time of 14
      months. We conclude that tumor cell purging using SBA in breast cancer patients
      is not warranted. New purging methods are needed to assess the role of tumor cell
      purging in breast cancer patients.

PMID- 9256904
TI  - Measuring health status in patients with skeletal metastases treated by surgery.
AB  - Since the introduction of the Functional Living Index-Cancer (FLIC) > 10 years
      ago, a variety of general as well as disease-specific quality of life (QOL)
      instruments have been developed and used as a means of assessing the success of
      clinical interventions. Clinicians faced with selecting an appropriate QOL
      measurement tool will need guidance in both the selection of the instrument and
      its evaluation for applicability to the patient group under study. In our
      examination of this issue, we analyzed the results of administering the FLIC and
      the more general SF-36 questionnaire to a group of 17 patients who had undergone
      orthopaedic surgery to correct problems associated with bone metastatic cancer.
      Because the SF-36 has been widely adopted as a general Health Status evaluation
      tool and because of its extensive validation it may be considered a gold standard
      providing a means of assessing the validity of disease-specific instruments such
      as the FLIC. Using multivariate regression, we built a model in which five of the
      eight health status dimensions of the SF-36 account for 77% of the variation in
      the FLIC scores for this group of patients (R2 = 0.77). The implication of this
      result is that most of the information (i.e., 77%) provided by the FLIC could be
      equivalently obtained using the more general, more widely validated SF-36.
      Despite the small sample size, half of the regression coefficients in this model
      achieved a high level of statistical significance (p < 0.001). In addition, when
      applied to new patients, the model showed good predictive capability with
      relative error 2-20%. If these results can be replicated for other patient
      disease groups and in larger study populations, it may be possible to use the SF
      36 as the primary QOL evaluation tool for cancer patients. The burden of this
      disease could then be more easily compared with that of other disease groups and
      the resulting standardization of QOL analysis would be simpler and more cost
      effective.

PMID- 9256905
TI  - Docetaxel. A review of its role in breast cancer treatment.

PMID- 9256906
TI  - Acute renal failure in a patient receiving treatment with suramin.
AB  - Suramin has demonstrated modest activity against prostate cancer and is being
      investigated in clinical trials. We describe a patient with metastatic prostate
      cancer who developed nonoliguric renal failure during treatment with suramin.
      Other potential causes of renal failure were not present in our patient and his
      renal function gradually recovered with the cessation of suramin treatment. Acute
      renal failure should be recognized as a potential complication of suramin
      treatment.

PMID- 9256907
TI  - Ethics in medical practice. With special reference to dermatologic surgery.
      American Society for Dermatologic Surgery.

PMID- 9256908
TI  - Does inflammation contribute to the eradication of basal cell carcinoma following
      curettage and electrodesiccation?
AB  - BACKGROUND: Curettage and electrodesiccation (C&D) is probably the technique most
      frequently utilized by dermatologists to treat basal cell carcinomas (BCC). From
      histologic studies, it appears C&D does not completely mechanically remove all
      nests of BCC in a substantial number of cases. Nevertheless, the reported 5-year
      reoccurrence rate following C&D is significantly less than this histologically
      observed residual tumor frequency immediately following C&D. Among the multiple
      possibilities that exist to explain why these residual nests do not appear as
      recurrent tumor more frequently is the theory that inflammation developing after
      C&D clears residual tumor. OBJECTIVE: To test the hypothesis that inflammation
      developing after C&D clears residual tumor not mechanically removed by the
      procedure. METHODS: The frequency of residual BCC detected histologically
      immediately following C&D was compared with the frequency 1 month after the C&D,
      an amount of time in which an effect (if any) of inflammation could occur.
      RESULTS: Twenty-two of 29 primary BCC < 1 cm treated by C&D were tumor free
      immediately following the procedure (clearance rate, 75.9%). Eleven of 14 primary
      BCC < 1 cm treated by C&D then allowed to granulate 1 month before excision and
      histologic analysis were tumor free, for a clearance rate of 78.6%. Examination
      of larger tumors immediately following C&D revealed size is a significant
      variable for clearance rates. Eleven primary BCC > 1 cm but < 2 cm were examined
      histologically immediately following C&D; only three were tumor free for a
      clearance rate of 27.3%. Only one of five tumors > 2 cm thus treated was tumor
      free, for a clearance rate of 20%. Nine recurrent BCC of various sizes were
      treated by C&D and immediately examined histologically. Two were tumor free for a
      clearance rate of 22.2%. Two recurrent BCC were allowed to heal 1 month following
      C&D; one of these was tumor free when excised. CONCLUSION: For primary BCC < 1
      cm, no evidence was found that inflammation occurring over 1 month following C&D
      clears residual tumor. It was also noted that C&D fails to completely remove
      tumor in a large majority of primary BCC > 1 cm, and in recurrent BCC.

PMID- 9256909
TI  - Cryogen spray cooling during Nd:YAG laser treatment of hemangiomas. A preliminary
      animal model study.
AB  - BACKGROUND: Successful laser treatment of hemangiomas requires selective
      photothermal destruction of dilated cutaneous vessels without damaging the
      overlying epidermis. Delivering a short cryogen spurt, on the order of
      milliseconds, has been shown to result in localized cooling of the superficial
      skin structures during laser irradiation. OBJECTIVE: The purpose of this study
      was to examine the effectiveness of cryogen spray cooling (CSC) in protecting
      superficial tissue structures during continuous Nd:YAG laser irradiation of an in
      vivo model hemangioma. METHODS: The highly vascularized chicken comb was selected
      as the animal model for hemangiomas. The Nd:YAG laser irradiation ranged from 2.6
      to 35.1 J/mm2. A feedback system utilizing infrared radiometry monitored the comb
      surface temperature and controlled delivery time of the cryogen spurt. When comb
      surface temperature during laser irradiation reached 36-42 degrees C, a 30-100
      msec cryogen spurt was delivered. Animals were euthanized 1 hour to 21 days
      following each experiment. Gross and histologic analyses were performed. RESULTS:
      Nd:YAG laser irradiation resulted in deep (up to 6.1 mm) tissue photocoagulation,
      while CSC preserved the overlying epidermis and papillary dermis. CONCLUSION: The
      results demonstrate that CSC is effective in protecting the epidermis and
      papillary dermis, while achieving deep tissue photocoagulation during Nd:YAG
      laser irradiation. Further pilot studies in humans appear warranted.

PMID- 9256910
TI  - Treatment of periorbital wrinkles. A comparison of the SilkTouch carbon dioxide
      laser with a medium-depth chemical peel.
AB  - BACKGROUND: Chemical peels are an effective treatment for wrinkles, but their use
      is limited because of the associated risk of scarring, hypopigmentation, and the
      inability to accurately control the depth of tissue injury. High energy, pulsed,
      or computer scanned continuous wave carbon dioxide (CO2) lasers cause minimal
      thermal injury, decrease the risk of scarring, and allow for precise control of
      tissue vaporization to predictable depths. OBJECTIVE: To compare the
      effectiveness and side effect profile of a medium-depth chemical peel to that of
      the SilkTouch CO2 laser in the treatment of periorbital wrinkles. METHODS: Twenty
      four subjects (nine male, 15 female) with moderate to severe periorbital wrinkles
      were assigned a wrinkle score (1 = mild through 5 = severe) before treatment and
      6 months after treatment. Each subject was treated with Jessner's solution and
      35% trichloroacetic acid on one side and the SilkTouch CO2 laser on the other
      side. RESULTS: The average periorbital wrinkle score decreased from 4.00 +/- 0.78
      before laser treatment to 1.75 +/- 0.68 6 months after treatment. The chemical
      peel wrinkle score decreased from 4.13 +/- 0.85 to 3.29 +/- 0.99. The degree in
      which the wrinkle score improved after laser treatment compared with after
      chemical peel treatment was statistically significant. Posttreatment erythema
      lasted an average of 4.5 months for the laser-treated areas and 2.5 months for
      the chemical peel-treated areas. CONCLUSION: Treatment of periorbital wrinkles
      with the SilkTouch CO2 laser resulted in a greater degree of improvement than
      treatment with a medium-depth chemical peel but had longer lasting posttreatment
      erythema.

PMID- 9256911
TI  - Current status of melanoma vaccines.
AB  - BACKGROUND: Malignant melanoma is increasing worldwide faster than any other
      cancer and the American lifetime risk is estimated to reach 1 in 75 by the year
      2000. Active specific immunotherapy with vaccines is evolving as a promising new
      modality in the treatment of malignant melanoma. OBJECTIVE: To present a concise
      and understandable summary of the key molecular and clinical concepts of melanoma
      vaccines currently under investigation, the history that led to their
      development, and their anticipated clinical response. METHODS: The recent
      advances in the field of melanoma immunobiology and the newest experiment
      vaccines are reviewed. RESULTS: There is no effective melanoma vaccine that
      successfully treats or prevents melanoma. However, their use has been associated
      with regression or delayed disease progression in some cases. The minority of
      patients who do have a major clinical response to vaccine therapy experience an
      improvement in survival. Even in those patients in whom melanoma vaccines cannot
      improve survival, the paucity of severe side effects has provided a quality of
      life superior to standard multiagent chemotherapy. CONCLUSION: Melanoma vaccines
      are relatively safe immunotherapeutic modalities for the management of malignant
      melanoma. The clinical effectiveness of melanoma vaccines is unclear and
      adequately controlled studies need yet to be performed. Current melanoma vaccines
      manipulate antigen presentation networks and combine the best cellular and
      antibody antitumor immune response effective in mediating tumor protective
      immunity; these combination vaccines hold the most promise. The ideal melanoma
      vaccine will ultimately prevent melanoma.

PMID- 9256912
TI  - Effect of dynamic cooling on 585-nm pulsed dye laser treatment of port-wine stain
      birthmarks.
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to determine the
      effectiveness of a dynamic cooling device (DCD), spraying the skin with a brief
      spurt of cryogen prior to the laser pulse, in reducing transient pain associated
      with 585-nm pulsed dye laser (PDL) treatment of port-wine stains (PWS), and
      reducing epidermal damage (hypo/hyperpigmentation) caused by this laser during
      PWS treatment. MATERIALS AND METHODS: Matched treatment sites were compared with
      and without the use of the cryogen spray in 47 patients at two investigational
      sites. Pain ratings, clearance of the PWS, and pigmentation changes were
      assessed. The results were analyzed by skin type and patient age. RESULTS: A
      statistically significant reduction in pain ratings was found in all patient
      groups using the DCD without changing the efficacy of PWS clearance. Pain
      reduction was most remarkable in patients with darker skin types. Dynamic cooling
      prevented the occurrence of epidermal damage or pigmentation change in most
      cases. CONCLUSIONS: This study suggests that dynamic cooling can dramatically
      diminish pain during PWS treatment with the 585-nm PDL without reducing treatment
      efficacy. The absence of epidermal damage in most patients suggests that
      precooling with the DCD may allow the use of higher laser fluences to expedite
      clearance without inducing epidermal change. Dynamic cooling has potential use
      with other lasers and different lesions where discomfort and epidermal effects
      limit therapy.

PMID- 9256913
TI  - The medical necessity for treatment of port-wine stains.
AB  - BACKGROUND: Port-wine stains are congenital vascular malformations that can be
      disfiguring and may lead to psychosocial as well as medical complications. The
      585-nm pulsed dye laser is very effective in treating port-wine stains. Laser
      treatment is often viewed by insurance companies as a "cosmetic procedure" and
      not "medically necessary". Consequently many patients are denied coverage for
      treatment of their disfiguring birthmarks. OBJECTIVE: To determine variability of
      insurance coverage for laser treatment of port-wine stains from state to state.
      Natural history, progression, and potential complications of port-wine stains are
      reviewed and rationale for consistent insurance coverage for laser treatment of
      port-wine stains is given. METHODS: A questionnaire was mailed to 40 dermatologic
      surgeons in 22 states and the District of Columbia. We reviewed the literature
      regarding port-wine stains and their potential complications, and health care
      policy guidelines regarding "medical necessity" and "cosmetic procedures".
      RESULTS: Insurance coverage for laser treatment of port-wine stains varies from
      state to state. CONCLUSION: Based on current health care policy guidelines, laser
      treatment of port-wine stains should be regarded, and covered, as a medical
      necessity by all insurance providers.

PMID- 9256914
TI  - Topical anesthetic agents in dermatologic surgery. A review.
AB  - BACKGROUND: The ideal topical anesthetic agent is one that provides 100%
      anesthesia in a short period of time, work on intact skin without systemic side
      effects, and invokes neither pain nor discomfort. The quest to find such an agent
      continues today. Because a topical anesthetic agent will induce anesthesia
      painlessly, the need for an effective agent is clear. This will serve to
      eliminate painful injections with lidocaine prior to many dermatologic
      procedures. OBJECTIVE: To provide a review of topical agents used in the past, to
      present products that are being used today, and to look to the future of topical
      anesthesia. CONCLUSIVE: During the last three decades a variety of methods have
      been employed to administer topical anesthesia. Presently, EMLA (eutectic mixture
      of local anesthetics) is the most often used method among practicing
      dermatologists. However, iontophoresis and the anesthetic patch are equally
      effective with a few notable advantages over EMLA. Liposomal agents show promise
      as we enter into a new millennium.

PMID- 9256915
TI  - Skin resurfacing with the erbium:YAG laser.
AB  - BACKGROUND: Recent studies have shown that pulsed char-free carbon dioxide lasers
      are effective in the treatment of rhytids. However, these lasers produce thermal
      damage with the potential for prolonged wound healing. OBJECTIVE: In this study,
      we evaluated the role of the erbium (Er):YAG laser in the treatment of rhytids.
      This laser, with a wavelength of 2940 nm, produces little thermal damage.
      METHODS: Twenty patients were treated with the Er:YAG laser. Perioral,
      periorbital, and forehead rhytids were treated. Pulsed of energy varying between
      400 and 800 mJ were used; spot sizes between 2.5 and 5 mm were chosen. Patients
      were evaluated at 2 days, 1 month, and 2 months for erythema, time of healing,
      degree of improvement, and pigmentary charges. RESULTS: All 20 patients showed
      improvement of their rhytids. Reepitheliation occurred between 4 and 10 days.
      Postoperative of eythema resolved in less than 2 weeks. Clinical improvement
      occurred between 3 and 8 weeks after laser treatment. CONCLUSION: The Er:YAG
      laser plays a role in the treatment of superficial rhytids.

PMID- 9256916
TI  - Citric acid increases viable epidermal thickness and glycosaminoglycan content of
      sun-damaged skin.
AB  - BACKGROUND: Recently, there has been an exponential increase in the use of alpha
      hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic
      preparations underscores their popularity. Among the clinical effects of alpha
      hydroxy acids are their ability to prevent the atropy resulting from potent
      topical corticosteroids, improve the appearance of photoaged skin, and correct
      disorders of keratinization. Despite this range of desirable effects, very little
      is known about the specific changes produced by various alpha-hydroxy acid
      preparations in the epidermis and dermal extracellular matrix. Previous work by
      others has demonstrated the ability of another alpha-hydroxy acid to increase
      viable epidermal thickness, and dermal glycosaminoglycans. OBJECTIVE: In this
      study, we examined the effect of 20% citric acid lotion, as compared with vehicle
      alone, on skin thickness, viable epidermal thickness, and dermal
      glycosaminoglycan content. Biopsy samples were harvested after 3 months of
      treatment. RESULTS: Image analysis of biopsy sections revealed increases in
      viable epidermal thickness and dermal glycosaminoglycans in treated skin.
      CONCLUSIONS: Topical citric acid produces changes similar to those observed in
      response to glycolic acid, ammonium lactate, and retinoic acid including
      increases in epidermal and dermal glycosaminoglycans and viable epidermal
      thickness. Further studies of citric acid and other alpha-hydroxy acids are
      warranted to clarify their clinical effects and mechanisms of action.

PMID- 9256918
TI  - Clinical and histologic evaluation of polyiodinated iodine with and without
      hypertonic saline/dextrose in the rabbit ear vein model.
AB  - BACKGROUND: Certain types of varicose veins can be successfully sclerosed with
      polyiodinated iodine (PII). Although this sclerosant is widely used in Canada and
      in Europe, it is not marketed in the United States. OBJECTIVE: The following
      study was undertaken to determine whether an American polyiodinated iodine (APII)
      formula, compounded in a hospital pharmacy, is as effective as a commercially
      available brand of PII in the rabbit ear vein model. The two sclerosants were
      identical in composition. METHODS: After being mixed with either normal saline
      (NS), Sclerodex, or an American dextrose-hypertonic solution (ADHS) compounded in
      a hospital pharmacy, each sclerosant was injected in concentrations of 0.1% and
      0.5%. The veins were examined clinically and histologically 1 hour, and 2, 8, and
      28 days after injection. They were examined with electron microscopy at 8 and 28
      days. RESULTS: When diluted with NS, Sclerodex, or ADHS and injected in a 0.1%
      concentration, each sclerosant produced a hyperplastic regenerating endothelium
      without evidence of mixed cellular infiltrates at 2 days. By 28 days, the
      endothelium was regenerated. When diluted with NS, Sclerodex, or ADHS and
      injected in a 0.5% concentration, each sclerosant produced more thrombosis,
      yielding a mild perivascular mixed cellular infiltrate and fibrin coagulum at 8
      days and thrombus cord formation at 28 days. CONCLUSION: When mixed with NS,
      Sclerodex, or ADHS, APII has the same efficacy as PII.

PMID- 9256917
TI  - Transforming growth factor-beta and bcl-2 distribution patterns distinguish
      trichoepithelioma from basal cell carcinoma.
AB  - BACKGROUND: Trichoepithelioma (TE) and basal cell carcinoma (BCC) have many
      features in common both clinically and histologically. Despite these many
      similarities TE and BCC represent different biological entities. OBJECTIVE:
      Recently, bcl-2 and CD34 have been reported as reliable markers in distinguishing
      the two types of tumor. Transforming growth factor-beta (TGF-beta), a
      multifunctional regulator of both cell growth and differentiation, was evaluated
      in this study. METHODS: The immunohistochemical expression of TGF-beta was
      compared with the distribution patterns of bcl-2 and CD34 in five BCCs, five TEs,
      and seven borderline cases. RESULTS: All five TEs showed a diffuse cytoplasmic
      staining of tumor cells for TGF-beta, whereas four of five BCCs were TGF-beta
      negative. Of the seven equivocal cases of TE/BCC, five tumors demonstrated TGF
      beta positivity in combination with negative bcl-2 staining corresponding to TE.
      The remaining two cases demonstrated the opposite staining pattern,
      characteristic for BCC. CONCLUSION: The TGF-beta staining pattern appears to be a
      helpful additional marker together with bcl-2 in differentiating between TE and
      BCC. The demonstrated staining differences may relate to the distinct origin and
      biological behavior of the two tumors and may therefore be of value in subsequent
      patient management.

PMID- 9256919
TI  - Laser hair removal in a patient with hypertrichosis lanuginosa congenita.
AB  - BACKGROUND: Hypertrichosis lanuginosa congenita (HLC) is a cutaneous disorder
      marked by diffuse lanugo-like hair present at birth. Although affected
      individuals are usually healthy, the excessive hair creates an extraordinary
      appearance. Permanent eradication of their superfluous hair is therefore a
      priority. However, a procedure that would achieve this objective is not currently
      available. OBJECTIVE: To evaluate the efficacy of a new laser technique for hair
      reduction in a patient with HLC. METHODS: Selected sites were repeatedly treated
      with a neodymium:YAG (Nd:YAG) laser subsequent to application of a topical carbon
      based solution. RESULTS: Forty to eighty percent hair reduction was noted in the
      sites treated. CONCLUSION: Topical solution-assisted Q-switched Nd:YAG laser hair
      removal is a safe and effective method for reducing hair density in cases of
      extensive hypertrichosis. It is an attractive method for children because the low
      fluences used minimize the associated pain.

PMID- 9256920
TI  - Multiple trichoepitheliomas successfully treated with a high-energy, pulsed
      carbon dioxide laser.
AB  - BACKGROUND: Multiple trichoepitheliomas are transmitted in an autosomal dominant
      fashion and can be clinically disfiguring. As with other dermal tumors,
      destructive techniques such as cryotherapy, electrodesiccation, and radiation
      therapy can improve the cosmetic appearance, but each of these treatments carries
      a significant risk of side effects and recurrence. OBJECTIVE: We describe a
      patient with a severe case of recurrent multiple trichoepitheliomas following
      excision, cryotherapy, and electrodesiccation. RESULTS: Treatment with a high
      energy, pulsed carbon dioxide laser produced an excellent clinical response with
      no recurrence noted in the treated area for 12 months. CONCLUSION: Laser
      vaporization of trichoepitheliomas using a pulsed carbon dioxide delivery system
      may provide superior clinical results without scanning and evidence of regrowth.

PMID- 9256921
TI  - Stump the experts. Cellular dermatofibroma.

PMID- 9256922
TI  - Dermabrasion and premalignant disease.

PMID- 9256923
TI  - Nitrous oxide cryosurgery applied to skin cancers.

PMID- 9256924
TI  - Maintenance cost vs utilization of medical lasers.

PMID- 9256925
TI  - New camouflaging technique following laser resurfacing.

PMID- 9256926
TI  - Cancer mortality among petroleum refinery and chemical manufacturing workers in
      Texas.
AB  - Epidemiologic historical cohort studies of petroleum refinery and chemical
      manufacturing workers in Texas were reviewed to examine their cancer mortality in
      comparison to the U.S. and to assess the possible impact of cancer mortality
      among these workers on the State of Texas as a whole. Summary standardized
      mortality ratios and 95% confidence intervals were calculated for 20 cancer
      types, taking into account the heterogeneity of individual studies. There were
      4314 cancer deaths among the 92,318 workers employed in 10 independent plant
      populations. Overall, there was a significant deficit in cancer mortality among
      petrochemical workers compared with the general U.S. population (SMR = 88, 95% CI
      = 80 to 96). Only the summary SMRs for brain cancer (SMR = 113, 95% CI = 96 to
      133) and leukemias (SMR = 112, 95% CI = 94 to 130) approached statistical
      significance. Lung and liver cancer mortality excesses, noted for Texas as a
      whole, were decreased in these workers. Additional follow-up of these cohorts,
      their expansion to include minority and female workers, and additional study of
      possible occupational contributions to leukemia and brain cancer are recommended.

PMID- 9256927
TI  - Expression of transforming growth factor beta in radiation interstitial
      pneumonitis.
AB  - We investigated the changes in transforming growth factor beta 1 (TGF-beta 1)
      mRNA and TGF-beta 3 protein expression that occur in radiation interstitial
      pneumonitis. We used TGF-beta 1-cDNA probe in situ hybridization and TGF-beta 3
      polyclonal antibody in immunohistochemical techniques. Our results showed that
      the distribution of TGF-beta 1 mRNA and TGF-beta 3 protein basically coincided in
      blood vessels, airways, lung parenchyma, and alveolar macrophages. However,
      bronchial epithelial cells expressed only TGF-beta 3 proteins and no TGF-beta 1
      mRNA. We found an increased expression of TGF-beta 1 mRNA and TGF-beta 3 proteins
      in radiation interstitial pneumonitis.

PMID- 9256928
TI  - Bioactivation of promutagens by the unicellular green alga Chlamydomonas
      reinhardtii.
AB  - The aromatic amine 2-aminofluorene (2-AF) was activated by the intact
      Chlamydomonas reinhardtii cells to a mutagen that exhibited toxic and mutagenic
      effects comparable to those of the direct-acting mutagen N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG). There were different responses of the wildtype and
      repair-deficient strains to the toxic and mutagenic effect of 2-AF. The
      recombination repair plays a major role in repair of damages induced in the C.
      reinhardtii DNA by the aromatic amine promutagen 2-AF and the direct-acting
      mutagen MNNG. The 2-AF activation has also been analyzed by algal cells/microbe
      coincubation assay. This new assay is used in addition to animal microsome
      metabolizing system (S9 fraction) and plant cell/microbe coincubation assay. This
      additional system is suitable for detection of environmental promutagens and
      their conversion to mutagens, mainly in aquatic environments.

PMID- 9256929
TI  - Loss of high-molecular-weight proteins in liver microsomes of rats treated with
      hepatocarcinogens.
AB  - Microsomal preparations from rats treated with 2-acetylaminofluorene (2-AAF) or
      with 4-dimethylaminoazobenzene (4-DAB), alone or followed by phenobarbital (PB),
      showed almost complete loss of microsomal proteins of molecular weights higher
      than 60,000, as shown by Sephadex G-150 gel filtration technique. Induction of a
      number of microsomal proteins in the lower ranges of molecular weights was also
      recorded due to the treatment of these two hepatocarcinogens with and without the
      use of PB as a promoter. These modifications in the protein patterns of
      microsomes might be due to altered genetic expression resulting in uncontrolled
      cell division/cell cycle.

PMID- 9256930
TI  - The use of the glial fibrillary acidic protein (GFAP) biomarker as an early
      detection model of chemically induced cancer.
AB  - Due to the massive industrial development during recent decades, the general
      population today is exposed to numerous environmental chemicals not only through
      occupational exposure but also through the daily handling and consumption of
      products. In our study, we developed a carcinogenesis bioassay for industrial
      solvents and other pollutants by measuring the gliosis produced by these toxins.
      We investigated the morphological changes produced by some pollutants in
      astroglial rat cultures and the increase in GFAP-positive cells. Astroglial
      primary cultures were obtained from the cerebral hemispheres of neonatal rats.
      The nutrient medium consisted of Waymouth's medium supplemented with 20% fetal
      calf serum and antibiotics. The cultures were incubated at 37 degrees C in a
      humidified particle-filtered room containing an atmosphere of 5% CO2 in air.
      After being cultured for 22 days, toluene and a mixture of solvents (toluene,
      carbon tetrachloride, and 1,1,1-trichloroethylene) were applied in concentrations
      between 10(-4) M and 10(-6) M. Immunofluorescence staining for glial fibrillary
      acidic protein (GFAP), a specific marker for fibrillary astrocytes, was only
      occasionally positive in the monolayer of the control cultures; however, it was
      markedly positive in most cells maintained for 3 or 9 days and exposed to toluene
      and mixed solvents. This study provides a rapid in vitro assay by which cells
      exposed to chemicals can be examined.

PMID- 9256931
TI  - Selenium levels in breast milk and cow's milk: a preliminary report from Saudi
      Arabia.
AB  - We measured the selenium in 117 milk samples by means of inductively coupled
      plasma spectrometry with the hydride t-system. The samples were collected from
      healthy lactating mothers living in the Al-Kharj area in Saudi Arabia and from
      seven brands of Saudi fresh cow's milk. The concentration of selenium in breast
      milk significantly decreases toward the end of lactation. Our results also showed
      that the selenium concentration in breast milk is also influenced by the number
      of breast feedings per day. Further studies are needed to evaluate the selenium
      status in Saudi infants. The selenium concentration in local cow's milk samples
      was significantly higher than in the breast milk samples.

PMID- 9256932
TI  - The effect of dietary selenium on lead neurotoxicity.
AB  - Lead, when administered to male rats for 8 weeks in a dose of 20 mg/kg body
      weight, resulted in the impairment of the enzymes hexokinase and total ATPase in
      the cerebral and cerebellar regions of the brain. The changes were, however, more
      pronounced in the cerebellar region. Along with these, a decrease in
      acetylcholine esterase (AchE) and monoamine oxidase (MAO) was seen, thus
      affecting both cholinergic and adrenergic neurotransmitters. When selenium was
      administered concomitantly with lead, the values of total ATPase and hexokinase
      activities approached normal values in both brain regions. A significant
      improvement in acetylcholine esterase activity and MAO was also seen.

PMID- 9256933
TI  - Sublethal effects of hexavalent chromium on the body growth rate and liver
      function enzymes of phenobarbitone-pretreated and promethazine-pretreated
      rabbits.
AB  - Hepatotoxic effects of chromium have been studied on the liver function enzymes
      of male New Zealand white rabbits, Oryctolagus cuniculus, with and without
      pretreatment with phenobarbitone (PB) and promethazine (PM). The total body
      weight was decreased under all experimental conditions. After PB administration
      (5 mg/kg body wt/day for 5 days), the serum glutamate oxaloacetate transaminase
      (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and
      isocitrate dehydrogenase (ICDH) activities decreased 21%, 65%, 25%, and 37%,
      respectively, whereas the alkaline phosphatase (AP) activity increased 70%. After
      PM treatment (5 mg/kg body wt/day for 5 days) the serum GPT was inhibited 73%,
      whereas LDH activity was increased 37%. The hepatic GPT and AP activities
      decreased after PB (52% and 31%, respectively), and PM (48% and 44%,
      respectively) treatments, whereas the activities of LDH and ICDH increased (after
      PB: 817% and 109%, respectively, and after PM: 136% and 44%, respectively).
      Potassium dichromate, administered at a dose of 8 mg/kg body wt/day for 5 days,
      decreased serum GOT (44%), GPT (61%), LDH (63%), and AP (44%) activities. The
      hepatic GOT, GPT and AP activities were likewise decreased (86%, 51%, and 46%,
      respectively), whereas hepatic LDH and ICDH activities increased 667% and 193%,
      respectively. When administered to PB-pretreated animals, the serum GOT and AP
      activities were decreased (50% and 68%), whereas ICDH was increased (29%). The
      hepatic GOT, LDH, and ICDH activities increased 79%, 221%, and 130%,
      respectively. In the PM-pretreated animals, the chromium treatment inhibited the
      activities of serum GOT (48%), GPT (44%), and LDH (43%). The hepatic GPT, LDH,
      and ICDH activities increased 90%, 133%, and 52%, respectively.

PMID- 9256934
TI  - Growth and toxigenesis of Aspergillus flavus isolates on selected spices.
AB  - None of the four Aspergillus flavus isolates studied was able to grow on wet
      cinnamon (5 g cinnamon + 3.3 mL distilled water) at 25 degrees C over 30 days.
      Fungal growth was weak on the curcumin, black pepper, and white pepper; good, but
      lower than on rice control, on the cumin and ginger; and similar to the control
      on sweet and hot paprika. No aflatoxin was detected in black or white pepper
      after 10 days at 25 degrees C. Cumin least inhibited aflatoxin synthesis,
      followed by hot paprika, cumin, sweet paprika, and ginger. The amount of
      aflatoxin detected in the spices at the end of the incubation period never
      exceeded 6.25% of that found in the rice control.

PMID- 9256935
TI  - Histopathological changes in the testes of prepubertal male rats after chronic
      administration of cocaine.
AB  - PURPOSE: This study was conducted to evaluate histopathologic findings in the
      testes of prepubertal male rats after long-term cocaine exposure. METHODS: At 25
      days of age, male Sprague-Dawley rats were administered cocaine hydrochloride
      daily (15 mg/kg body weight corresponding to an average single dose for a heavy
      cocaine user). The treatment was continued for 100 days when all the rats were
      sacrificed. Morphological analysis of the testes were assessed by qualitative and
      quantitative histological means. RESULTS: In all the groups, a minimum of 5 to 10
      representative seminiferous tubules were examined. The mean diameter of the
      seminiferous tubules was less in the treated group than in their respective
      controls (p < 0.05). The thickness of the germinal epithelium was much reduced in
      the cocaine-treated groups when compared with their controls (p < 0.05). The
      number of degenerating germ cells was greater in the treated group than in the
      controls. There was evidence of failure to release the mature spermatids in the
      treated groups. There was no evidence of sloughed Sertoli cells or germ cells in
      the tubular lumen or the epididymis. CONCLUSION: There were distinct
      histopathological changes noted after chronic administration of cocaine. These
      changes are characteristic of toxic effects on the testes, but the exact
      mechanism is not clear. Further studies are underway in our laboratory to
      delineate the exact mechanism of action by cocaine on the testes.

PMID- 9256936
TI  - Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1
      infected patient.
AB  - BACKGROUND: Recent research has found that entry of non-syncytium-inducing (NSI),
      monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5
      receptors, and that delta 32/delta 32 homozygous individuals are protected
      against infection. OBJECTIVE: To analyse the polymorphism of CCR-5 gene in HIV-1
      infected and uninfected subjects. DESIGN AND METHODS: CCR-5 sequences were
      amplified by polymerase chain reaction (PCR) from DNA of peripheral blood
      mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected
      controls were tested for the detection of the 32 base-pair deletion. HIV-1
      phenotype was determined by viral isolation and MT-2 evaluation. RESULTS: The
      wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were
      represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1
      infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the
      CCR-5 gene was detected by PCR and sequencing confirmed in a patient with
      progressive infection harbouring a clade B virus with SI phenotype. CONCLUSIONS:
      delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute
      protection against HIV-1 infection, suggesting that either macrophage-tropic
      viral strains could use coreceptors other than CCR-5 or infect independently of
      the presence of a functional CCR-5 coreceptor. Alternatively, primary infection
      sustained by T-cell-tropic isolates, although exceptional, may occur.

PMID- 9256937
TI  - Targeted and general population interventions for HIV prevention: towards a
      comprehensive approach.

PMID- 9256938
TI  - HIV phenotype switching during antiretroviral therapy: emergence of saquinavir
      resistant strains with less cytopathogenicity.
AB  - OBJECTIVES: The aim of the study was to investigate changes in virological
      characteristics of HIV strains isolated from 38 HIV-seropositive subjects during
      antiretroviral therapy. DESIGN AND METHODS: Patients with a CD4+ cell count < or
      = 300 x 10(6)/l were treated with zidovudine (12 individuals) and saquinavir (10
      individuals) alone or in combination (16 individuals). CD4+ cell count, viral
      load, HIV biological phenotype and drug resistance were evaluated during the
      study period. RESULTS: After 52 weeks, 28 subjects (74%) harboured drug-resistant
      strains. In patients with a syncytium-inducing (SI) strain, a decline of CD4+
      cell count and an increase of viral load were observed aside from the emergence
      of drug resistance. Conversely, at the emergence of antiretroviral resistance, an
      immunological and virological deterioration was observed only in patients who had
      a non-syncytium-inducing (NSI) strain. During the study, a phenotype switching of
      HIV isolates was detected in eight (21%) patients and a temporal correspondence
      between the appearance of phenotype switching and the emergence of drug
      resistance was found in seven cases. Three patients harbouring saquinavir
      resistant strains showed a switch from SI to NSI variants associated with a
      moderate increase in CD4+ cell count. CONCLUSIONS: The emergence of resistant
      strains during antiretroviral therapy may be associated with the selection of
      viral strains with less cytopathogenicity, while it could become a poor
      prognostic sign in patients with NSI isolates.

PMID- 9256940
TI  - The RGD-containing domain of exogenous HIV-1 Tat inhibits the engulfment of
      apoptotic bodies by dendritic cells.
AB  - OBJECTIVE: HIV-1 Tat can be released by infected cells and exert various
      extracellular functions on bystander cells, possibly contributing to
      immunodeficiency. In order to investigate whether exogenous Tat can affect
      antigen presentation, the effects of synthetic Tat on the function of dendritic
      cells displaying antigen presenting cell phenotype were studied. DESIGN: Cultured
      dendritic cells were challenged with apoptotic bodies and monitored for cell
      engulfment and free intracellular calcium ([Ca2+]i) increase. The effect of
      synthetic HIV-1 Tat and its RGD-containing domain (peptide 65-80) or basic domain
      (peptide 46-60) on both functions was investigated. METHODS: Dendritic cells were
      obtained by culture of monocytes with granulocyte-macrophage colony-stimulating
      factor. Apoptosis was induced in Jurkat cells by sub-lethal irradiation.
      Engulfment of radiolabelled apoptotic bodies by dendritic cells was obtained by a
      45 min co-incubation at 37 degrees C. Non-ingested apoptotic bodies were removed
      and cell-associated radioactivity evaluated in a gamma-counter after cell lysis.
      Single cell analysis of calcium fluxes was performed by video-microscopy and
      ratio-imaging, after cell staining with the fluorescent calcium chelator FURA-2.
      RESULTS: Apoptotic bodies were engulfed by dendritic cells: this process was
      accompanied by [Ca2+]i rise. Synthetic HIV-1 Tat inhibited both apoptotic body
      engulfment and [Ca2+]i increase. The same inhibition was obtained with the RGD
      containing domain (peptide 65-80), but not with the basic domain (peptide 46-60)
      of Tat, suggesting the involvement of an integrin. This integrin is likely to be
      alpha v beta 3, since RGD-containing peptides from vitronectin, but not from
      fibronectin, inhibited apoptotic body engulfment. Furthermore, both HIV-1 Tat and
      its 65-80 peptide blocked [Ca2+]i increase due to beta 3-integrin cross-linking.
      CONCLUSIONS: Our results support a role for HIV-1 Tat in decreasing the function
      of dendritic cells, possibly impairing antigen presentation.

PMID- 9256939
TI  - Induction of apoptosis by primary HIV-1 isolates correlates with productive
      infection in peripheral blood mononuclear cells.
AB  - OBJECTIVE: To study the apoptosis-inducing capacity of HIV-1 primary isolates in
      human peripheral blood mononuclear cells (PBMC) in relation to the viral
      biological phenotype. DESIGN AND METHODS: Four HIV-1 primary isolates capable of
      replicating and inducing syncytia in the MT-2 cell line and two primary isolates
      lacking these properties were used to infect PBMC with the same infectious doses.
      The kinetics of virus production in the culture supernatants were followed in
      relation to apoptosis induction in PBMC as determined by intracellular labelling
      of apoptotic DNA strand breaks and flow cytometry analysis. RESULTS: When low
      virus dose was used (0.001 m.o.i.), productive virus infection, with peak reverse
      transcriptase (RT) activity at days 5-7, was followed by high numbers of
      apoptotic cells at day 10 post infection. Tenfold higher inoculum dose (0.01
      m.o.i.) resulted in enhanced virus production with peak RT activity at day 3
      followed by high numbers of apoptotic cells at day 5 after infection. The
      apoptosis-inducing capacity of virus isolates was independent of their capacity
      to induce syncytia or replicate in the MT-2 cell line. However, upon
      cocultivation of infected PBMC with MT-2 cells, only virus with the MT-2 tropic
      phenotype initiated productive infection and induced apoptosis in MT-2 cells.
      CONCLUSIONS: These results show that apoptosis induction in PBMC by primary HIV-1
      isolates is closely related to the kinetics of virus replication but is not
      influenced by other biological properties of the virus such as syncytium-inducing
      capacity and MT-2 tropism.

PMID- 9256941
TI  - Transmission between HIV-infected patients of multidrug-resistant tuberculosis
      caused by Mycobacterium bovis.
AB  - OBJECTIVE: To investigate outbreaks of multidrug-resistant tuberculosis (TB) by
      using DNA fingerprint databases. DESIGN: Investigation of two outbreaks of
      multidrug-resistant TB in separate hospitals in Spain by restriction fragment
      length polymorphism (RFLP) and spoligotyping. Outbreak strains were compared with
      more than 1500 RFLPs of Mycobacterium tuberculosis complex strains isolated in
      Spain and 6000 RFLPs from 30 different countries. METHODS: Standardized IS6110
      DNA fingerprinting and 'spoligotyping' was used to type multidrug-resistant
      isolates belonging to the M. tuberculosis complex amongst the outbreak cases. The
      DNA types were matched against DNA fingerprint databases in Spain and The
      Netherlands. RESULTS: The DNA typing analysis indicated that a single multidrug
      resistant Mycobacterium bovis strain was responsible for a nosocomial outbreak in
      a hospital in Spain involving at least 16 HIV-infected patients with non
      treatable to multidrug-resistant TB. Introduction of the fingerprint type of this
      strain to the international database revealed a single matching strain. This
      strain was also isolated from an HIV-infected patient in The Netherlands who had
      died from multidrug-resistant TB. This patient had previously been hospitalized
      in Spain, where a multidrug-resistant TB nosocomial outbreak involving 20 HIV
      infected patients was ongoing. The strains causing this outbreak were also
      identified as M. bovis with an identical DNA pattern to those strains isolated in
      the Spanish hospital and the patient in The Netherlands. CONCLUSIONS: The use of
      centralized DNA databases can help to identify rapidly the origin and
      transmission routes of multidrug-resistant TB across international boundaries and
      the potential use of such an early warning surveillance system for investigation
      of nosocomial multidrug-resistant TB outbreaks between HIV-infected patients. To
      our knowledge this is the first report of transmission of multidrug-resistant M.
      bovis between hospitals.

PMID- 9256942
TI  - Prior antimicrobials and staphylococcal bacteremia in HIV-infected patients.
AB  - OBJECTIVE: Many drugs used for prophylaxis against opportunistic infections in
      AIDS also have activity against common bacteria. This study was performed to
      delineate relationships between prior use of antimicrobials and Staphylococcus
      aureus bacteremia. DESIGN: To compare prior exposure to selected antimicrobial
      drugs in patients who had S. aureus bacteremia and in controls who did not, a
      nested case-control study was conducted within a cohort of HIV-infected persons
      followed in an outpatient clinic. METHODS: Using a computerized database based on
      HIV clinic records, 48 cases with S. aureus bacteremia were compared against 188
      controls selected from patients with CD4 cell counts < 200 x 10(6)/l. Information
      on demographic risk factors and antimicrobial drug use was analysed using
      conditional logistic regression. RESULTS: Injecting drug use was strongly
      associated with S. aureus bacteremia. Rifabutin use was associated with decreased
      risk of S. aureus bacteremia [conditional relative risk (RR) 0.308, 95%
      confidence interval (CI) 0.096-0.991] in univariate analysis, near statistical
      significance in multivariate analysis (RR 0.314, 95% CI 0.096-1.023). The
      bacteremias were not significantly associated with use of trimethoprim
      sulfamethoxazole, quinolones, newer macrolides (azithromycin and clarithromycin),
      clindamycin or dapsone. CONCLUSIONS: Rifabutin may be associated with diminished
      risk of S. aureus bacteremia incidental to use for other purposes in HIV
      infection. Further study is needed to assess effects on microbial resistance.

PMID- 9256944
TI  - The influence of drug use patterns on the rate of CD4+ lymphocyte decline among
      HIV-1-infected injecting drug users.
AB  - OBJECTIVES: To assess the relationship between various injecting drug use
      patterns and the rate of CD4+ lymphocyte decline in HIV-1-infected injecting drug
      users in Baltimore, Maryland, USA. METHODS: A cohort of 605 HIV-1-infected
      injecting drug users was recruited between 1988 and early 1989 in East Baltimore
      using extensive community outreach techniques. The participants were interviewed
      semi-annually to collect information on drug use practices. The outcome measure
      of interest was the rate of CD4+ lymphocyte decline between pairs of CD4+
      lymphocyte counts. A mixed model was used to evaluate the relationship between
      the change in CD4+ lymphocyte count per month and previous CD4+ lymphocyte count
      and various drug use variables. RESULTS: The 605 HIV-infected injecting drug
      users had a median initial CD4+ lymphocyte count of 513 cells x 10(6)/l. Using
      3209 paired observations, the mean change in CD4+ lymphocyte count was -3.2 cells
      x 10(6)/l per month. The rate of decline was higher in those with a higher level
      of CD4+ lymphocytes (P < 0.01) and length of drug use (P < 0.01), but did not
      vary by injection frequency or injection intensity of specific drug types.
      Although animal studies have suggested that the pattern of drug administration
      (continuous versus intermittent) and episodes of withdrawal or overdose might
      impact the rate of CD4+ lymphocyte decline, this was not observed in the present
      study. CONCLUSION: Patterns of injecting drug use, based on self-report, were not
      associated with the rate of decline in CD4+ lymphocytes.

PMID- 9256943
TI  - Effect of antiviral treatment on the shedding of HIV-1 in semen.
AB  - OBJECTIVE: The potential role of antiretroviral treatment on the infectiousness
      of HIV-1-infected men was examined by studying the effect of antiviral treatment
      on the shedding of HIV-1 in semen. METHODS: Forty-four patients enrolled in
      various treatment protocols were asked to donate a semen sample before they began
      a new antiviral treatment and at a follow-up visit after 6 to 15 weeks of
      treatment. Since most patients were on blinded protocols, patients were
      stratified by response of blood viral load. The effect of each patient's
      treatment was classified as good (n = 24), fair (n = 8) and marginal (n = 13) by
      measurement of the HIV RNA reduction in blood plasma (> 1.0 log10; 0.5-1.0 log10
      and < 0.5 log10 HIV RNA copies/ml reduction, respectively). The effect of
      treatment on shedding of HIV-1 in semen was documented by the reduction of HIV
      RNA concentration in seminal plasma and by quantitative HIV-1 seminal cell
      culture. RESULTS: Overall, antiviral treatment resulted in a significant fall in
      the viral load in semen (RNA and culture) that paralleled the reduction of viral
      load in blood. More pronounced reductions of HIV RNA in semen were observed as
      the effectiveness of treatment on blood HIV RNA levels increased (median drop
      from baseline 0, 0.3 log10 and 0.8 log10 RNA copies/ml in patients with marginal,
      fair and good treatment effect, respectively). Thirteen patients lost detectable
      HIV RNA in blood on treatment and all of these had undetectable levels of HIV-1
      in semen by culture and RNA analysis at follow-up. In 19 of the 31 patients (62%)
      who still had HIV RNA in their blood during treatment, semen HIV levels were
      below detection in semen at follow-up. CONCLUSIONS: Treatment-induced changes of
      HIV RNA concentration in blood are generally associated with a corresponding
      change in seminal HIV RNA: If confirmed in larger studies, potent antiretroviral
      therapy might reduce the spread of HIV-1.

PMID- 9256945
TI  - Prevention of Pneumocystis carinii pneumonia: who are we missing?
AB  - OBJECTIVE: To obtain population-based information on the characteristics of
      persons who were not receiving chemoprophylaxis against Pneumocystis carinii
      pneumonia (PCP) by examining the use of primary and secondary PCP prophylaxis
      among San Francisco residents whose AIDS-defining opportunistic illness was PCP
      in 1993. DESIGN: Retrospective medical record review. SETTING: Medical charts
      were obtained from San Francisco hospitals and outpatient facilities at which
      AIDS patients received their initial AIDS diagnosis. PARTICIPANTS: San Francisco
      residents whose AIDS-defining opportunistic illness was PCP in 1993. MAIN OUTCOME
      MEASURES: Use of primary and secondary PCP prophylaxis. RESULTS: Of the 326
      eligible patients, 35% received primary PCP prophylaxis. Non-whites were
      significantly less likely to have received primary PCP prophylaxis than white
      patients [22 versus 40%, respectively; odds ratio (OR), 0.49; 95% confidence
      intervals (CI), 0.28-0.87]. Uninsured individuals-were also less likely to have
      received primary PCP prophylaxis than those with insurance (18 versus 41%; OR,
      0.35; 95% CI, 0.17-0.73). The sociodemographic characteristics of patients who
      did and did not receive secondary PCP prophylaxis did not differ significantly.
      The most frequently cited reasons for not receiving primary PCP prophylaxis were
      that patients were unaware of their infection with HIV or were not receiving
      regular medical care. CONCLUSIONS: Barriers to receipt of PCP prophylaxis exist
      and are resulting in cases of preventable disease and unnecessary medical costs.
      Interventions to increase counseling, testing, and referral to medical care for
      persons at high risk for HIV infection are needed.

PMID- 9256946
TI  - Recent upturn in mortality in rural Zimbabwe: evidence for an early demographic
      impact of HIV-1 infection?
AB  - OBJECTIVES: To describe recent mortality trends in rural Zimbabwe and to assess
      the impact of HIV-1 infection. METHOD: Comparative, cross-sectional,
      retrospective, demographic survey with 1-year follow-up. Parallel HIV-1
      surveillance. Comparison of results with 1992 national census and vital
      registration data and results from mathematical model-based population
      projections. SETTING AND PARTICIPANTS: Residents of 929 (745 revisited in 1995)
      households in two rural areas of Manicaland Province, Zimbabwe, with contrasting
      HIV-1 prevalence: Honde and Rusitu valleys. Subjects gave information on parental
      survival for 2320 resident children. Female residents aged 13-49 years (n = 1237)
      provided information on birth histories and child survival. Consenting women
      attending local antenatal clinics (n = 487) provided blood samples for HIV-1
      screening and demographic information. MAIN OUTCOME MEASURES: HIV-1 prevalence in
      pregnant women; per capita death registration rates; incidence of parental death
      for children aged under 8 years; infant mortality and age-specific death
      probabilities. RESULTS: HIV-1 prevalence was high in each study area. Death
      registration and age-specific mortality have begun to rise. The largest increases
      were seen in the area of higher HIV-1 prevalence (Honde) and among younger
      adults, particularly men. Incidence of parental death was observed to be rising.
      Increases in registered deaths were concentrated among HIV-1-associated causes.
      CONCLUSIONS: The observed increases in mortality by age, sex and cause of death
      were consistent with those expected early in a severe HIV-1 epidemic, on the
      basis of mathematical model projections and observations elsewhere in Africa.
      Further rises in mortality, particularly among women and young children, and
      consequent increases in orphanhood, are to be expected in rural areas of
      Zimbabwe.

PMID- 9256947
TI  - Survival with AIDS in Ireland.
AB  - OBJECTIVE: To analyse the pattern of survival for patients diagnosed with AIDS in
      Dublin. METHODS: Data on 193 patients visiting the Department of Genitourinary
      Medicine of a Dublin Hospital, over a period of 7 years with AIDS, were analysed,
      and survival patterns were investigated. RESULTS: The cumulative probability of
      survival for the cohort was 69.0 +/- 3.3% at 1 year and 6.5 +/- 2.5% at 5 years.
      Median survival was 576 days. Year of diagnosis and disease group to which the
      patient belonged at diagnosis had a significant influence on the survival of the
      cohort (P < 0.0006 and P < 0.02, respectively). Age group, disease group, and
      year of diagnosis showed significant differences between strata (P < 0.01, P <
      0.002, and P < 0.04, respectively). Patients aged 35-39 years showed longer
      median survival times (715 days) than all other age groups (median survival = 547
      days; P < 0.04). Patients whose disease group at diagnosis was opportunistic
      disease(s) alone (Centers for Disease Control 1987 criteria, stage IV group C1)
      had a significantly longer median survival (672 days) than all others (median
      survival 281 days; P < 0.0002). Survival did not differ significantly by sex or
      risk group alone, nor did it differ significantly by manifestation of disease
      when grouped according to recognised criteria. Treatment with antiretroviral
      therapy had a significant influence on the survival of the cohort (P < 0.0002),
      and the treatment group showed a significant difference between strata (P <
      0.0002). This result must be qualified by the fact that, first, 11 of the 26
      patients not receiving therapy died within 1 month of diagnosis and people who
      survived longer had a greater chance of beginning treatment, and that, secondly,
      criteria for antiretroviral therapy allocation were not entirely clear.
      CONCLUSIONS: The overall survival time found by this study is comparable to that
      found in other studies in developed countries of the survival of persons with
      AIDS. Patterns of survival for age groups and manifestation of disease show some
      contrasting features, mainly owing to the demographic profile of the patients and
      the high proportion of intravenous drug users.

PMID- 9256948
TI  - Intact CCR-5 coreceptors in HIV-1-infected chimpanzees.

PMID- 9256950
TI  - Hepatic steatosis and lactic acidosis associated with stavudine treatment in an
      HIV patient: a case report.

PMID- 9256949
TI  - Successful treatment of cytomegalovirus encephalitis in an AIDS patient using
      cidofovir.

PMID- 9256951
TI  - Detection of HIV-1 RNA in vaginal secretions of HIV-1-seropositive women who have
      undergone hysterectomy.

PMID- 9256952
TI  - HIV/AIDS surveillance in Colombia: regional differences in epidemic trends.

PMID- 9256953
TI  - No therapeutic advantage from didanosine (ddI) and hydroxyurea versus ddI alone
      in patients with HIV infection.

PMID- 9256954
TI  - Reduction of Kaposi's sarcoma lesions following treatment of AIDS with ritonovir.

PMID- 9256955
TI  - Hypersensitivity reactions during antiretroviral regimens with protease
      inhibitors.

PMID- 9256956
TI  - Central nervous system as a sanctuary for HIV-1 infection despite treatment with
      zidovudine, lamivudine and indinavir.

PMID- 9256957
TI  - Macrophage-tropism of HIV-1 isolates of different genetic subtypes.

PMID- 9256958
TI  - Relation between serologic response and pathologic findings in sheep with
      naturally acquired paratuberculosis.
AB  - OBJECTIVE: To investigate the relation between lesions and serologic response in
      sheep with naturally acquired paratuberculosis and to evaluate the efficacy of
      agar gel immunodiffusion (AGID) and ELISA as diagnostic tests. ANIMALS: 134 adult
      sheep, culled by the owner from flocks with history of severe chronic weight
      loss. PROCEDURE: Before euthanasia, blood samples were collected and serum was
      obtained. AGID and ELISA were performed, using a protoplasmic antigen of
      Mycobacterium paratuberculosis. Sensitivity and specificity of these techniques
      were evaluated, using histopathologic findings as a reference. Histologic studies
      were carried out focusing on specimens containing intestinal organized lymphoid
      tissue. RESULTS: Of the sheep examined, 46.3% had lesions that were classified in
      5 categories, according to their location, extension, cellular types, and
      presence of acid-fast bacilli. Regarding serologic test results, 37.1% of sheep
      with lesions had a positive AGID result, and all sheep without lesions had
      negative results. However, ELISA positivity was slightly greater--48.4% of sheep
      with lesions; however, by use of ELISA, 11.1% of sheep without lesions had
      positive results. CONCLUSION: A close relation between pathologic findings and
      serologic response was determined, especially between presence of acid-fast
      bacilli (potentially heavily shedding sheep) in the intestinal lesions and
      positivity to serologic tests, especially AGID. CLINICAL RELEVANCE: On the basis
      of these results, together with its high specificity, reliability, and the
      difficulty of fecal specimen culture in sheep, AGID is proposed as a useful tool
      for seeking evidence of paratuberculosis in live sheep, and therefore, is
      suggested as the basis for control programs in areas in which the disease is a
      serious threat to sheep production.

PMID- 9256959
TI  - Comparison of nested polymerase chain reaction, virus isolation, and fluorescent
      antibody testing for identifying feline herpesvirus in cats with conjunctivitis.
AB  - OBJECTIVE: To compare nested polymerase chain reaction (PCR), virus isolation
      (VI), and fluorescent antibody (FA) testing to detect feline herpesvirus (FHV) in
      cats with naturally acquired conjunctivitis or respiratory tract disease, or
      both. SAMPLES: Swab and microbrush specimens from the conjunctiva and throat were
      taken from 46 cats, allotted to 3 groups (conjunctivitis only, respiratory tract
      disease and conjunctivitis, and clinically normal). PROCEDURE: Cells from
      microbrush specimens were digested and herpesvirus DNA was amplified, using a
      double round of PCR. Products were detected by use of agarose gel
      electrophoresis. The VI and FA tests were performed in routine manner. RESULTS:
      Of 16 cats with conjunctivitis only, conjunctival specimens from 8 and throat
      specimens from 8 were FHV positive by PCR. None had positive results of VI or FA
      testing. Of 15 cats with respiratory tract disease and conjunctivitis,
      conjunctival specimens from 13 and throat specimens from 12 were FHV positive by
      PCR. A conjunctival specimen from 1 cat and throat specimens from 3 cats were FHV
      positive by VI. A conjunctival specimen from 1 cat was FHV positive by FA
      testing. Of 15 clinically normal cats, conjunctival and throat specimens from 2
      cats were FHV positive by PCR; neither conjunctival nor throat specimens from
      these cats were FHV positive by VI or FA testing. CONCLUSION: For cats with
      respiratory tract disease and conjunctivitis, or with conjunctivitis only, nested
      PCR was more sensitive at detecting FHV than was VI or FA testing. CLINICAL
      RELEVANCE: Nested PCR is a more sensitive test than the currently available VI
      and FA tests for identifying FHV in cats with conjunctivitis.

PMID- 9256960
TI  - Serum concentrations of zinc and copper in bull terriers with lethal
      acrodermatitis and tail-chasing behavior.
AB  - OBJECTIVE: To establish similarities or differences in tissue concentrations of
      zinc, copper, and iron in Bull Terriers with lethal acrodermatitis (LAD) and tail
      chasing behavior (TCB) and to confirm the suspicion that copper is involved in
      the etiopathogenesis of LAD. SAMPLES: Serum samples from 29 Bull Terriers (9
      control dogs, 6 dogs with LAD, 14 dogs with TCB), and liver and kidney specimens
      from 2 dogs and 1 and 4 dogs with LAD or TCB, respectively. PROCEDURE: Serum,
      liver, and kidney mineral (zinc, copper, and iron) concentrations in Bull
      Terriers with LAD or TCB and in a group of control dogs were analyzed, using
      flame atomic absorption after wet ashing technique. RESULTS: Serum zinc and
      copper concentrations were lower (P < 0.05) in dogs with LAD, compared with
      values for control dogs and dogs with TCB. Liver zinc and copper concentrations
      were similar to serum values. Kidney zinc and copper concentrations were similar
      among the 3 groups. Serum, liver, and kidney iron concentrations had a wide range
      of variability within all 3 groups. CONCLUSION: Copper deficiency is associated
      with LAD. The primary cause of LAD may be copper deficiency, with zinc involved
      secondarily, or combined zinc and copper deficiencies. The role of ion deficiency
      in TCB was not clarified. CLINICAL RELEVANCE: Serum zinc and copper
      concentrations should be determined when LAD is suspected.

PMID- 9256961
TI  - Secretion of apolipoprotein A-I by calf liver parenchymal cells.
AB  - OBJECTIVE: To determine: whether apolipoprotein A-I (apoA-I) is secreted by calf
      liver parenchymal cells; the isoprotein pattern and association with lipids of
      secreted apoA-I; and effects of steroid hormones on apoA-I secretion. SAMPLE
      POPULATION: 6 male Holstein calves (1 to 2 weeks old) as a cell culture source.
      PROCEDURE: apoA-I in culture medium was detected by immunoblot analysis, and its
      concentration was measured by use of an ELISA. The isoprotein pattern was
      analyzed by use of two-dimensional polyacrylamide gel electrophoresis.
      Associations of apoA-I with cholesterol and phospholipids were examined by
      ultracentrifugal analysis of the culture medium. RESULTS: Concentration of apoA-I
      in culture medium increased linearly up to 24 hours. The protein synthesis
      inhibitors, actinomycin D and cycloheximide, suppressed apoA-I accumulation in
      the medium in dose-dependent manner. Molecular mass of this protein in culture
      medium was 28 kd, and was indistinguishable from apoA-I of plasma. Four
      isoproteins with different isoelectric points (1 = 5.75; 2 = 5.67; 3 = 5.58; and
      4 = 5.46) were detected. Of these, isoprotein 2 was the major species. By
      comparison, isoprotein 4 was the predominant species in plasma, and isoprotein 5
      (isoelectric point = 5.38) was newly detected instead of isoprotein 1.
      Approximately 33% of apoA-I in culture medium was found in lipid-rich fractions,
      whereas the rest was found in nonlipoprotein fractions. Dexamethasone (10(-8) to
      10(-6) M) significantly (P < 0.001) increased apoA-I concentration in the medium,
      and the stimulatory effect was significantly (P < 0.001) suppressed by the
      simultaneous addition of 10(-6) M progesterone. Progesterone itself (10(-8) to
      10(-5) M) had little effect on apoA-I secretion; estradiol (10(-14) to 10(-8) M)
      also had no significant effect. CONCLUSIONS: apoA-I is synthesized by calf liver
      parenchymal cells, and the secreted protein is modified during circulation.
      Moreover, apoA-I synthesis and secretion by the cells appear not to be largely
      influenced by hormones, except for dexamethasone.

PMID- 9256962
TI  - Distribution of glycoconjugates in the uterine tube (oviduct) of horses.
AB  - OBJECTIVE: To examine glycoconjugates in the isthmic and ampullar regions of the
      uterine tube (oviduct) of horses during estrus, diestrus, and pregnancy. SAMPLE
      POPULATION: Oviductal samples from 17 mares. PROCEDURE: Oviducts were collected
      during estrus (n = 3), diestrus (n = 3), or pregnancy (n = 3), embedded, and snap
      frozen in liquid nitrogen. Frozen sections (5 to 6 microns in thickness) were
      stained with 100 micrograms/ml of fluorescein-isothiocyanate-conjugated lectin
      (30 min at 38.5 C) and were evaluated by use of epifluorescence microscopy and
      video image analysis. Specificity of lectins was established by blocking with the
      corresponding carbohydrate. Dolichos biflorus agglutinin (DBA)-affinity studies
      on western blots of oviductal lavage fluid, oviductal explant conditioned media,
      and apical membrane proteins from isthmic and ampullar regions of oviducts were
      used to identify glycoproteins with galactosyl residues. RESULTS: Use of 4
      lectins resulted in differential labeling of the luminal surface of the oviductal
      epithelium. Both DBA and soybean agglutinin labeled the apical epithelium of the
      isthmus, but not the ampullar oviduct. Soybean agglutinin resulted in more
      intensely labeled epithelium in the isthmic region of oviducts during estrus and
      pregnancy than during diestrus. The DBA labeled a number of glycoproteins in
      conditioned media from both regions of the oviduct. These glycoproteins ranged
      from 14 to 200 kd, with major glycoproteins identified at 31 and 57 kd.
      CONCLUSIONS: The predominant glycoconjugates in the oviduct of horses are
      galactosyl residues. There are regional differences in the distribution of these
      galactosyl glycoconjugates in the isthmic and ampullar oviduct.

PMID- 9256963
TI  - Detection of activated platelets and platelet-leukocyte aggregates in horses.
AB  - OBJECTIVE: To determine the potential usefulness of tests for detection of
      platelet activation and platelet-leukocyte aggregates in horses. SAMPLES: Blood
      from 3 healthy Thoroughbreds. PROCEDURES: Microscopic and flow cytometric assays
      were used to evaluate spontaneous platelet aggregation, platelet activation, and
      platelet-leukocyte aggregates. Platelet activation was detected by evaluation of
      binding of anti-human fibrinogen to unactivated and ADP-, thrombin-, thrombin
      agonist receptor peptide-, and platelet activating factor-activated platelets.
      Platelet-leukocyte aggregates were evaluated microscopically and by flow
      cytometric determination of leukocyte fluorescence that resulted from binding of
      fluorescently labeled platelets to leukocytes. RESULTS: Equine platelets readily
      aggregated spontaneously when blood was stirred at low, medium, and high speeds.
      Compared with unactivated platelets, activated platelets had a marked increase in
      the percentage of cells with increased fluorescence intensity and in mean
      fluorescence intensity. Unactivated platelets formed aggregates with neutrophils
      and monocytes, but not with lymphocytes. Activation of platelets resulted in a
      calcium-dependent increase in platelet-leukocyte aggregates. CONCLUSIONS: Flow
      cytometric techniques can be used to detect in vitro platelet activation and
      platelet-leukocyte aggregates in horses. CLINICAL RELEVANCE: Flow cytometric
      techniques may be useful for detection of prothrombotic disorders in horses.

PMID- 9256964
TI  - Airborne transmission of Actinobacillus pleuropneumoniae and porcine reproductive
      and respiratory syndrome virus in nursery pigs.
AB  - OBJECTIVE: To document airborne transmission of Actinobacillus pleuropneumoniae
      and porcine reproductive and respiratory syndrome virus (PRRSV) infection in
      nursery pigs. ANIMALS: 32 two-week-old pigs obtained from 3 farms, but with
      similar Landrace X Yorkshire genetics for trial 1 of each experiment; 16 pigs for
      trial 2 of the A pleuropneumoniae experiment; and 14 pigs for trial 2 of the
      PRRSV experiment. PROCEDURE: In experiment 1, pigs were inoculated with A
      pleuropneumoniae serotype 1 (6/8) or were left as contacts (2/8). At the
      beginning of trial 1, pigs were seronegative to A pleuropneumoniae serotypes 1
      and 5 on the basis of results of an ELISA, but had positive results on the A
      pleuropneumoniae hemolysin I (Apx1)-neutralization test. Pigs in trial 2 had
      negative results on both tests. Pigs of trial 1 of experiment 2 were inoculated
      with a PRRSV virulent field isolate (MN-1b); pigs of trial 2 were inoculated with
      the virus reference strain VR-2332. Aerosol-exposed pigs were placed on the other
      side of the air duct and kept there for 2 to 7 weeks depending on evidence of
      airborne transmission. RESULTS: In trial 1 of experiment 1, evidence of airborne
      transmission was not found. In trial 2, most airborne-exposed pigs died as a
      result of A pleuropneumoniae infection 12 days after initiation of the
      experiment. In trial 1 of experiment 2, all inoculated pigs (8/8) seroconverted,
      but only 2 of 8 contact-exposed pigs seroconverted. Aerosol-exposed pigs did not
      seroconvert nor was virus isolated. In trial 2, all inoculated and contact
      exposed pigs seroconverted. All aerosol-exposed pigs seroconverted after 21 days,
      and virus was isolated at 16 days. CONCLUSIONS: A pleuropneumoniae was
      transmitted by air at a distance of 1 m when pigs were fully susceptible to the
      organism. Transmission of PRRSV appeared to be strain dependent; when reference
      strain VR-2332 was used, airborne transmission of PRRSV was documented.

PMID- 9256965
TI  - Protection of dogs against canine distemper by vaccination with a canarypox virus
      recombinant expressing canine distemper virus fusion and hemagglutinin
      glycoproteins.
AB  - OBJECTIVES: To evaluate the safety and efficacy of a live canarypox virus
      recombinant-canine distemper virus (CDV) combination vaccine against virulent CDV
      challenge exposure, and to document lack of interference among the other modified
      live virus (MLV) components. ANIMALS: 33 specific-pathogen-free (SPF) Beagle pups
      (7 to 10 weeks old). PROCEDURE: A canarypox virus recombinant-CDV combination
      vaccine was tested for safety and efficacy along with MLV components (canine
      adenovirus type 2, canine coronavirus, canine parainfluenza virus, and canine
      parvovirus) in 26 SPF Beagle pups. The combination vaccine was rehydrated with
      either Leptospira canicola-L icterohaemorrhagiae combination bacterin (vaccine 1)
      or sterile diluent (vaccine 2). An additional group of 7 seronegative SPF pups
      received the control MLV components devoid of the combination vaccine (vaccine
      3). Two vaccinations were administered 21 days apart, either IM or SC. The dose
      of the combination vaccine used to inoculate these pups was 40 times lower than
      the recommended commercial dose. At 21 days after the booster vaccination, all
      pups were challenge exposed with a virulent CDV strain, then were observed for 21
      days to record morbidity and mortality. RESULTS: Adverse local or generalized
      reactions were not induced by vaccinations. All vaccinates seroconverted to CDV.
      Serum antibody titers to MLV components were not different, with or without
      inclusion of the combination vaccine. After challenge exposure, morbidity and
      mortality in vaccinates were 0% (0/26); in control dogs, values were 100%
      morbidity and 86% mortality (6/7). Brain impression smear slides made from all
      dogs that did not survive challenge exposure were CDV positive by use of a direct
      fluorescein isothiocyanate method. CONCLUSIONS: The canarypox virus-CDV
      combination vaccine, administered SC or IM, is a safe product that elicits CDV
      seroconversion, does not interfere with other vaccine components, and protects
      vaccinated pups against virulent CDV challenge exposure.

PMID- 9256966
TI  - Evaluation of an animal rabies vaccine by use of two types of potency tests.
AB  - OBJECTIVE: To evaluate the potency of an inactivated animal rabies vaccine for
      domestic animals by use of 2 types of potency tests after challenge exposure with
      a laboratory standard virus or 1 of 5 viruses obtained from various wildlife
      species. ANIMALS: 384 mice vaccinated twice intraperitoneally; 384 mice
      vaccinated once IM. PROCEDURE: Mice vaccinated with an inactivated, adjuvanted
      rabies vaccine for domestic animals were challenge exposed with the common fixed
      challenge virus or 1 of 5 rabies viruses obtained from wild animal species
      (street viruses) that most commonly transmit the virus in the United States and
      Canada. Potency tests included 2 types of antigen extinction tests: the National
      Institutes of Health (NIH) test and the Centers for Disease Control test.
      RESULTS: Results of both tests indicated that protection was highest against
      raccoon and bat viruses. Marked differences were detected in the relative potency
      ratios for the NIH versus the Centers for Disease Control tests, though the
      relative potencies themselves (against the street viruses) did not differ
      markedly. CONCLUSIONS: The markedly reduced potency against the street viruses
      indicated by the NIH test results was suggestive of an inherent bias associated
      with double intraperitoneal vaccination and intracerebral challenge exposure,
      whereas the single IM vaccination and IM challenge exposure reduced that bias.

PMID- 9256968
TI  - Efficacy of imidacloprid for removal and control of fleas (Ctenocephalides felis)
      on dogs.
AB  - OBJECTIVE: To evaluate efficacy of a 9.1% (w/w) imidacloprid solution, applied
      topically, to remove fleas from dogs and the duration of residual flea control
      when dogs were exposed to continuing flea infestation. ANIMALS: 32 adult mixed
      breed dogs. PROCEDURE: Dogs were allocated to 4 groups of 8 dogs each; dogs of 3
      groups received a single dose of imidacloprid, and those of the fourth group
      received excipient. Each dog was infested with 100 adult fleas on study days -3, 
      1, 6, 13, 20, 27, and 33. Treatments were applied on day 0. Each dog was examined
      for live fleas on days -2, 1, 7, 14, 21, 28, and 34. Posttreatment efficacy was
      determined by comparing the mean number of live fleas remaining on the treated
      dogs with the mean number of live fleas remaining on the control dogs. RESULTS:
      All 3 imidacloprid dosages provided flea control > or = 96.9% one day after
      treatment. Maximal efficacy of all 3 dosages (99.1 to 100%) was observed at 7
      days after treatment. Flea control with 3.75 mg of imidacloprid/kg of body weight
      ranged from 94.4 to 96.9% for days 14 to 28 and decreased to 91.6% by 34 days
      after treatment. Flea control with 7.5 and 10.0 mg of imidacloprid/kg was 97.8 to
      100% through day 28. At day 34, dosages of 7.5 and 10.0 mg of imidacloprid/kg
      were 97.6 and 96.9% efficacious, respectively. CONCLUSION: 7.5 or 10.0 mg of
      imidacloprid/kg are equivalent and superior to 3.75 mg/kg for flea control over
      the course of a 34 day posttreatment period. CLINICAL RELEVANCE: Monthly
      imidacloprid application of 7.5 to 10 mg/kg will rapidly kill existing and
      reinfesting flea infestations on dogs and break the flea life cycle by killing
      adult fleas before egg production begins.

PMID- 9256967
TI  - Efficacy of a subcutaneously administered, ultraviolet light-killed Pasteurella
      multocida A:3-containing bacterin against transthoracic challenge exposure in
      goats.
AB  - OBJECTIVE: To determine the effectiveness of Pasteurella multocida biovar A,
      serovar 3 (Pm A:3) killed by exposure to UV light and incorporated with a
      polyacrylate bead carrier as a vaccine. ANIMALS: 18 weanling male Spanish goats.
      PROCEDURE: Prospective, randomized controlled study with 3 treatment groups:
      positive-control (PC), negative-control (NC), and principal Pm A:3 bacterin (PA)
      groups. Six PC goats each received live Pm A:3 and polyacrylate beads twice, 22
      days apart, by transthoracic injection into the left lung. Six NC goats each
      received only PA beads twice, 22 days apart, by transthoracic injection. Six
      principal goats each received Pm A:3 vaccine SC twice, 22 days apart. Fourteen
      days after the second vaccination, all goats were challenge exposed with live Pm
      A:3 by transthoracic injection into the right lung, and 4 days later they were
      euthanatized and necropsied. RESULTS: Mean volume of consolidated lung tissue at
      the challenge site was 1.75 cm3 for the PC group, 15.18 cm3 for the NC group, and
      3.9 cm3 for the PA vaccine group. The NC group had a significantly (P < or =
      0.002) larger mean volume of consolidated lung tissue than did the PC and PA
      groups after challenge exposure. CONCLUSIONS: The PA bacterin and the PC groups
      developed protective immunity against live Pm A:3 challenge exposure. An SC
      administered, UV light-killed, Pm A:3 bacterin induced protective immunity
      similar to that induced by virulent live Pm A:3 injected into the target organ,
      the lung.

PMID- 9256969
TI  - Effects of oral or intravenous inoculation with Brucella abortus strain RB51
      vaccine in beagles.
AB  - OBJECTIVES: To determine whether the vaccine Brucella abortus strain RB51 (SRB51)
      would infect dogs, be shed in urine or feces, or cause placentitis and abortion.
      ANIMALS: 18 Beagles. PROCEDURE: Males (n = 3), nonpregnant females (n = 3), and
      pregnant females (n = 4) were inoculated orally with SRB51; control dogs (n = 2)
      were fed sterile saline solution. A separate group of pregnant females (n = 5)
      received SRB51 i.v., and their controls (n = 1) received sterile saline solution
      i.v.. Dogs were observed twice daily for evidence of abortion. Urine and feces
      were collected periodically for bacteriologic culture, and blood was collected
      for bacteriologic culture and serologic analysis. At full gestation (oral and
      i.v. inoculated pregnant females) or on postinoculation day 49 (nonpregnant
      females and males), dogs were euthanatized and samples were collected for
      bacteriologic culture and microscopic examination. RESULTS: Abortion was not
      apparent during the study, and SRB51 was not found in samples of urine of feces
      from any dog. Strain RB51 was isolated from retropharyngeal lymph nodes from all
      orally inoculated dogs (9/9). One orally inoculated and 1 i.v. inoculated
      pregnant dog had SRB51 in placental tissues. Strain RB51 was also isolated from 1
      fetus from the orally inoculated female dog with placentitis, but lesions were
      not detected in the fetus. CONCLUSIONS AND CLINICAL RELEVANCE: Oral inoculation
      of nonpregnant female or male dogs with SRB51 did not result in shedding in urine
      or feces, although oropharyngeal lymph nodes became infected; in pregnant
      females, it caused infection of the placenta, with resulting placentitis and
      fetal infection, but abortion was not apparent. Intravenous inoculation resulted
      in infection of maternal spleen, liver, and placenta; however, fetal infection
      and abortion were not observed. Infected canine placental membranes or fluids may
      be a source of infection for other animals and human beings.

PMID- 9256971
TI  - Vitreous body glutamate concentration in dogs with glaucoma.
AB  - OBJECTIVE: To analyze the vitreal amino acid concentrations in dogs with breed
      related primary glaucoma to determine whether excitotoxic amino acids associated
      with retinal genglion cell death in other species were present in affected dogs.
      SAMPLES: 11 normal control and 10 glaucomatous canine eyes. PROCEDURE: Amino acid
      analyses were performed by high-pressure liquid chromatography in masked manner.
      RESULTS: Eyes from dogs with primary glaucoma had significantly high vitreal
      glutamate concentration, compared with values for eyes of clinically normal
      control dogs. Mean (+/-SD) glutamate concentrations were 31.7 +/- 12.4 and 6.9 +/
      6.3 microM in glaucomatous and normal eyes, respectively (P < 0.0001). Eyes from
      dogs with glaucoma also had lower vitreal glycine (37.0 +/- 17.0 vs 59.4 +/- 28.2
      microM; P < 0.043) and higher of vitreal tryptophan (39.0 +/- 22.8 vs 17.5 +/-
      11.2 microM; P < 0.012) concentrations, compared with values for normal eyes.
      CONCLUSION: Glutamate concentration potentially toxic to retinal ganglion cells
      is associated with the pathogenesis of primary glaucoma in dogs. Increased
      glutamate concentration provides evidence of an ischemic mechanism for retinal
      ganglion cell death and optic nerve atrophy in dogs with glaucoma. CLINICAL
      RELEVANCE: The emphasis on reduction and normalization of high intraocular
      pressure as the primary focus of treatment for glaucoma in dogs should be
      augmented by other therapeutic approaches.

PMID- 9256970
TI  - Overexpression of p53 tumor suppressor protein in spontaneously arising neoplasms
      of dogs.
AB  - OBJECTIVE: To determine prevalence of p53 tumor suppressor protein overexpression
      in spontaneously arising tumors of dogs, using the CM-1 polyclonal antibody and
      immunohistochemical methods. DESIGN AND SAMPLE POPULATION: Retrospective analysis
      was performed on archived, paraffin-embedded tumor tissue from dogs. A total of
      226 tumors were evaluated, including tumors of epithelial, mesenchymal, and round
      cell origins. PROCEDURES: Overexpression of p53 was detected by indirect
      immunohistochemical methods, using the CM-1 rabbit anti-human p53 polyclonal
      primary antibody. Protein overexpression was determined by use of a grading
      system based on percentage of stained tumor nuclei. RESULTS: Nuclear
      overexpression of p53 was detected in most squamous cell carcinomas, nasal
      adenocarcinomas, and perianal gland adenocarcinomas. Hemangiopericytomas,
      transitional cell carcinomas, mammary adenocarcinomas, apocrine gland
      adenocarcinomas, intestinal adenocarcinomas, mast cell tumors, and cutaneous
      histiocytomas had low numbers of nuclei overexpressing p53. Remaining tumor types
      had intermediate p53 nuclear overexpression. Cytoplasmic staining was observed in
      some carcinomas, particularly intestinal adenocarcinomas. CONCLUSIONS:
      Overexpression of p53 is common in spontaneously arising neoplasms of dogs.
      CLINICAL RELEVANCE: Prospective determination of p53 status in some tumor types
      may be as clinically useful in determining prognosis and predicting survival
      times for dogs with cancer as it is for human beings with cancer.

PMID- 9256972
TI  - Cortisol suppression in cats after induction of anesthesia with etomidate,
      compared with ketamine-diazepam combination.
AB  - OBJECTIVE: To evaluate duration and magnitude of adrenocortical function
      suppression after administration of etomidate to cats. ANIMALS: 15 purpose-bred,
      healthy cats. PROCEDURE: Cats were allotted to 2 groups. Anesthesia was induced
      with etomidate (ET, 2 mg/kg of body weight, i.v.; n = 8) or a mixture (KD, n = 7)
      of ketamine (5 mg/kg; i.v) and diazepam (0.25 mg/kg, i.v.). Anesthesia was
      maintained with halothane in all cats for 2 hours. ACTH gel (2.2 U/kg, i.m.) was
      administered 30 minutes after anesthesia induction. Blood samples for cortisol
      assay were taken before anesthesia induction (T -30), and before (T0) and at 30,
      60, 120, 180, 300, and 420 minutes after ACTH administration. Anesthesia was
      discontinued after the T120 sample was obtained. RESULTS: After anesthesia
      induction, median (interquartile range [Q1-Q3]) cortisol values were
      significantly lower in the ET group (4 [3 to 4] micrograms/dl) at T0, compared
      with T -30 values and with T0 values in the KD group (5 [3 to 9] micrograms/dl).
      After ACTH administration, cortisol values in the ET group continued to decrease
      two- to threefold below T -30 values and remained decreased over the 2-hour
      anesthesia period. After ACTH administration, cortisol values increased twofold
      for 2 hours in the KD group, compared with T -30 values. One hour after
      anesthesia recovery, cortisol values in the ET group (3 [2 to 3] micrograms/dl)
      remained significantly lower than values in the KD group (9 [7 to 11]
      micrograms/dl) and preanesthesia values. By T300, both groups had cortisol
      concentration near 7 micrograms/dl, similar to preanesthesia values. CONCLUSION:
      Induction of anesthesia with etomidate caused suppression of adrenocortical
      function during 2 hours of halothane anesthesia and 1 hour of recovery in cats.
      Cortisol concentration did not return to baseline until after 2 additional hours.
      CLINICAL RELEVANCE: Results from these healthy cats suggest profound suppression
      of important stress hormones after anesthesia induction with etomidate, use of
      which could put critically ill cats at further risk.

PMID- 9256973
TI  - Itraconazole disposition after single oral and intravenous and multiple oral
      dosing in healthy cats.
AB  - OBJECTIVE: To determine the disposition of itraconazole in cats after single IV
      and oral dosing (as a solution or capsule) and multiple oral (capsule) dosing,
      and to establish bioavailability after oral administration of the solution.
      ANIMALS: 6 healthy cats for experiment 1 (E1), and 12 cats for experiment 2 (E2).
      PROCEDURE: For E1 (nonrandomized crossover design), each cat received a single
      dose of itraconazole solution (5 mg/kg of body weight) orally, and 1 month later,
      another dose i.v.. Blood samples were collected for 96 hours. For E2, each cat
      was given either 5 (group [G] 1) or 10 (G2) mg of itraconazole/kg (capsules)
      twice daily for 6 weeks. Samples were collected for 96 hours after the first and
      last dose. Itraconazole was detected by use of high-performance liquid
      chromatography. RESULTS: For E1, itraconazole plasma drug concentration
      extrapolated to time zero (IV dose) was 5.2 +/- 1.4 micrograms/ml, and mean
      residence time (MRT) was 37 +/- 16 hours. For oral dosing, maximal itraconazole
      concentration was 1.69 +/- 0.864 micrograms/ml, MRT was 48 +/- 17 hours, and
      bioavailability was 78.8 +/- 28%. For the multiple oral dosing study, MRT (at
      last dose: 81.1 +/- 97.4 hours for G1, and 63.1 +/- 15.1 hours for G2) was
      shorter (P = 0.02) at first dose, compared with last dose, for both groups but
      did not differ between groups. Maximal concentration did not differ between
      groups at either time. Steady state was achieved at 14 to 21 days. All cats
      tolerated itraconazole with no evidence of adverse effects. CONCLUSIONS: The oral
      itraconazole solution is preferred to capsules; a 24-hour dosing interval should
      be sufficient; 10 mg/kg given daily should generate therapeutic concentrations in
      most cats; steady-state concentrations may take up to 3 weeks to achieve; and
      cats appear to tolerate itraconazole well.

PMID- 9256974
TI  - Age-related changes in the pharmacokinetic disposition of diazepam in foals.
AB  - OBJECTIVE: To evaluate changes in the pharmacokinetic disposition of diazepam in
      foals from 4 to 84 days of age. SAMPLE POPULATION: 4 male and 2 female full-term
      mixed-breed foals. PROCEDURE: Diazepam terminal half-life, volume of
      distribution, clearance, free fraction, unbound volume of distribution, free
      clearance, peak desmethyldiazepam concentration, and area under the
      desmethyldiazepam concentration-time curve were determined after i.v.
      administration of 0.25 mg of diazepam/kg of body weight to foals at 4, 21, 42,
      and 84 days of age. RESULTS: Disposition of diazepam was best described using a
      two-compartment model. Clearance and free fraction values (mean +/- SEM)
      determined at 4 days (5.06 +/- 0.79 and 51 +/- 8 ml/kg/min, respectively) were
      significantly less than those obtained at 21 (8.64 +/- 0.95 and 87 +/- 11
      ml/kg/min), 42 (7.31 +/- 0.82 and 83 +/- 10 ml/kg/min), and 84 (8.41 +/- 0.56 and
      100 +/- 12 ml/kg/ min) days. Volume of distribution and unbound volume of
      distribution values determined at 4 days (1.57 +/- 0.11 and 16.0 +/- 1.7 L/kg,
      respectively) were significantly less than those found at 21 (2.66 +/- 0.33 and
      26.8 +/- 3.9 L/kg), 42 (3.00 +/- 0.42 and 33.9 +/- 5.0 L/kg), and 84 (2.55 +/-
      0.35 and 30.2 +/- 5.3 L/kg) days. Peak plasma desmethyldiazepam concentration
      obtained at 4 days (22.7 +/- 2.4 ng/ml) was significantly lower than that
      obtained at 21 (36.1 +/- 4.5 ng/ml), 42 (38.3 +/- 4.8 ng/ml), and 84 (34.6 +/-
      2.1 ng/ml) days. CONCLUSIONS: Factors likely to affect the pharmacokinetic
      disposition of diazepam in foals, such as body composition and hepatic enzyme
      activity, are in transition during the first 21 days of life. These have opposing
      effects on diazepam clearance and volume of distribution so that terminal half
      life remains unchanged. However, clearance determines whether diazepam will
      accumulate with repeated doses, and care should be taken when administering
      repeated doses to foals < 21 days old.

PMID- 9256975
TI  - Comparative pharmacokinetics of caffeine and three metabolites in clinically
      normal horses and donkeys.
AB  - OBJECTIVE: To determine whether clearance of capacity-limited drugs in horses
      differs from that in donkeys by comparing the serum disposition of caffeine and
      its metabolites, theophylline, theobromine, and paraxanthine after i.v.
      administration of caffeine to horses and donkeys. ANIMALS: 4 healthy horses and 5
      healthy donkeys. PROCEDURE: Blood samples were collected from each animal at time
      0 (before) and 5, 10, 15, 20, 30, and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24,
      30, 36, 48, 54, 60, 72, and 96 hours after IV administration of a bolus of
      caffeine. Serum was analyzed in triplicate by high-performance liquid
      chromatography to determine caffeine, theophylline, theobromine, and paraxanthine
      concentrations. The serum concentration-time curves for each animal were analyzed
      separately to estimate model-independent pharmacokinetic variables. RESULTS: Mean
      pharmacokinetic values for caffeine, theophylline, and paraxanthine did not
      differ significantly in horses, compared with donkeys. Mean peak serum
      concentration of theobromine was significantly higher in donkeys, compared with
      horses. CONCLUSION: Clearance of the capacity-limited drug caffeine does not
      appear to differ in horses, compared with donkeys. CLINICAL RELEVANCE: For some
      drugs that undergo hepatic metabolism, the dose and dose interval used for horses
      may be appropriate for use in donkeys.

PMID- 9256976
TI  - Cardiopulmonary effects of sevoflurane, compared with halothane, enflurane, and
      isoflurane, in dogs.
AB  - OBJECTIVE: To evaluate cardiopulmonary effects of sevoflurane (Sevo), compared
      with halothane (Hal), enflurane (Enf), and isoflurane (Iso). ANIMALS: 24 healthy
      Beagles, randomly assigned to 4 groups of 6 dogs each. PROCEDURE: Dogs under
      spontaneous ventilation were anesthetized with Sevo, Hal, Enf, or Iso. After
      minimum elveolar concentration (MAC) of each anesthetic was determined,
      anesthesia was maintained at light (1 MAC), moderate surgical (1.5 MAC), and deep
      (2 MAC), stages and cardiopulmonary variables at conscious state (baseline) and
      each anesthesia stage were measured. RESULTS: In dogs of the Sevo group, heart
      rate increased significantly from the baseline value at all anesthesia stages.
      Systemic vascular resistance during Sevo anesthesia decreased gradually with
      increasing anesthesia stage, which was accompanied by dose-dependent decreases in
      systolic, mean, and diastolic arterial blood pressures. At 1.5 and 2 MAC Sevo,
      stroke index decreased slightly but significantly from the baseline value;
      however, cardiac index was unchanged because of the significant increase in heart
      rate. Respiratory rate decreased significantly at 2 MAC from that at 1 MAC Sevo.
      Tidal volume and dead space-to-tidal volume ratio were unchanged at all
      anesthesia stages of Sevo, resulting in significantly decreased expired and
      alveolar ventilation at 2 MAC, compared with values at 1 and 1.5 MAC Sevo. PaCO2
      increased and pHa decreased significantly, depending on anesthesia stage; PaO2,
      increased significantly from baseline values, and remained constant because of
      inhalation of 100% O2. CONCLUSION: Cardiovascular effects of Sevo were greater
      than those of Hal, similar to those of Iso, and less than those of Enf.
      Respiratory effects of Sevo were similar to those of Iso at all anesthesia
      stages, greater than those of Hal at 2 MAC, and less than those of Enf at 1.5 and
      2 MAC. Up to the moderate surgical anesthesia stage, Sevo can be used safely in
      dogs undergoing spontaneous ventilation.

PMID- 9256977
TI  - Hormonal modulation of the physiologic responses of calves infected with Eimeria
      bovis.
AB  - OBJECTIVE: To determine whether an estradiol-progesterone (EP) growth implant
      would have an effect on febrile responses and on the catabolic component of
      Eimeria bovis infection. ANIMALS: 27 Holstein bull calves. PROCEDURE: Calves were
      assigned to treatment groups as: control (n = 5), EP implant (EP, n = 5), E bovis
      inoculated (coccidia: C, n = 7), pair fed (n = 4), or EP plus E bovis-inoculated
      coccidia (EP/C, n = 6) groups. Calves were provided subcutaneous EP implants at 8
      weeks of age, and were inoculated with 2 x 10(5) oocysts of E bovis at 11 weeks
      of age. Body weight was measured on postinoculation day (PID) 0, 14, and 28.
      Rectal temperature and food intake were determined and fecal samples were
      collected daily from PID 15 to 28. Blood samples were collected on PID 24 for
      analysis of CD2+, CD4+, and CD8+ antigens and plasma insulin-like growth factor I
      concentration. Blood samples were collected at 15-minute intervals for
      measurement of pulsatile growth hormone release. RESULTS: Group-EP/C calves had
      fever for 2 days versus 5 days for group-C calves (P < 0.05). These calves had
      diarrhea for fewer days than did their group-C counterparts (P < 0.05).
      Fibrinogen and glucose values were high in group-C (P < 0.05) but not group-EP/C
      calves. The latter had positive weight gain from PID 14 to 28, whereas group-C
      calves had weight loss (P < 0.05). Plasma insulin-like growth factor I
      concentration was reduced by infection (P < 0.05). EP-treated noninfected calves
      had increased numbers of CD2+, CD4+, and CD8+ blood mononuclear cells (P < 0.05).
      CONCLUSIONS: EP has a protective effect in calves infected with E bovis. This may
      relate to changes in immune function induced by EP. CLINICAL RELEVANCE: Treatment
      of calves with EP could offer some protection against the often severe wasting
      and debilitation associated with E bovis infection.

PMID- 9256978
TI  - Effects of airway obstruction on transmural pulmonary artery pressure in
      exercising horses.
AB  - OBJECTIVE: To determine whether laryngeal hemiplegia would increase transmural
      pulmonary artery pressure (TPAP). ANIMALS: 6 horses. DESIGN: Horses were studied
      under 5 conditions: control conditions, after induction of left laryngeal
      hemiplegia, during obstruction of the left nostril, after placement of an
      instrumented tracheostomy, and after placement of an open tracheostomy. Horses
      were evaluated after being given saline solution and after being given
      furosemide. PROCEDURES: Horses were exercised on a high speed treadmill, using a
      maximum speed of 13 m/s. During each exercise, airway pressures, airflow,
      esophageal and pulmonary artery pressures, and blood gas partial pressures were
      measured. RESULTS: When adjusted for horse, speed, and obstruction condition,
      mean TPAP (pulmonary artery pressure-esophageal pressure) and minimum TPAP were
      significantly lower after administration of furosemide than after administration
      of saline solution. In horses given saline solution, respiratory obstruction that
      increased intrapleural pressure significantly increased mean TPAP, and
      respiratory obstruction that decreased intrapleural pressure significantly
      decreased minimum TPAP. CONCLUSIONS: Changes in intrapleural pressure appear to
      play an important role in pulmonary artery pressure and TPAP. CLINICAL RELEVANCE:
      Because induction of laryngeal hemiplegia did not increase TPAP, laryngeal
      hemiplegia is unlikely to contribute to development of exercise-induced pulmonary
      hemorrhage.

PMID- 9256979
TI  - Effects of halothane and sevoflurane on the electroretinogram of dogs.
AB  - OBJECTIVE: To study the effects of halothane and sevoflurane on the
      electroretinogram of dogs. ANIMALS: 6 clinically normal Beagles. PROCEDURE:
      Beagles were paralyzed by continuous IV administration of muscle relaxant and
      were artificially ventilated with a gas mixture of nitrous oxide and oxygen
      during experiments. Corneal electroretinograms were recorded, using full-field
      stimuli under several recording conditions before and during 1% halothane or 2%
      sevoflurane inhalation. RESULTS: The amplitude of the scotopic threshold response
      (STR) and b-wave was significantly decreased by halothane or sevoflurane
      inhalation, but the degree of decrease in the STR was much greater. In contrast,
      the amplitudes of oscillatory potentials were increased. The peak latencies of
      the 3 components tended to be prolonged by inhalation of the anesthetic. There
      seemed to be no difference between the effects of halothane and sevoflurane.
      CONCLUSIONS: Halothane and sevoflurane strongly depressed the STR in Beagles
      while moderately depressing the b-wave and increasing oscillatory potential
      amplitudes. Thus, neither is an appropriate anesthetic for use in recording of
      the STR in dogs.

PMID- 9256980
TI  - Use of jugular venous blood, compared with mixed venous blood, for measurement of
      venous oxygenation indices in a porcine model of endotoxic shock.
AB  - OBJECTIVE: To evaluate the reliability of oxygen saturation and oxygen content
      values measured from jugular venous blood in estimating values measured from
      mixed venous blood during endotoxic shock. ANIMALS: 14 random-bred 10- to 15-kg
      Yorkshire pigs. PROCEDURE: 60 pairs of heparinized blood samples were
      simultaneously collected from the pulmonary artery and right jugular vein during
      an independent study, using a porcine model of endotoxic shock. Endotoxic shock
      was induced by infusion of Escherichia coli endotoxin. Eighteen of the sample
      pairs were obtained from pigs prior to infusion of endotoxin or from control
      pigs. Oxygen saturation and venous oxygen content were measured by direct
      oximetry. Analysis of bias and precision was used to compare jugular venous blood
      values with values obtained from mixed venous blood. Samples from endotoxemic
      pigs were subclassified on the basis of abnormal states of global oxygen
      imbalance associated with septic shock. RESULTS: Indices of venous oxygenation
      measured from jugular venous blood were an imprecise method of estimating values
      measured from mixed venous blood. There was no significant difference in bias
      between nonendotoxemic and endotoxemic pigs, regardless of abnormal hemodynamic
      states. CONCLUSION: Jugular venous blood oxygen saturation and oxygen content
      values should not be used to assess global oxygen transport during endotoxic
      shock.

PMID- 9256981
TI  - Effects of flunixin meglumine on short circuit current in equine colonic mucosa
      in vitro.
AB  - OBJECTIVES: To study the effect of flunixin meglumine on short circuit current
      (Isc) in equine right ventral colon in vitro. SAMPLES: Intestinal mucosa from
      healthy horses and ponies. PROCEDURE: Isc was measured in mucosa from the right
      ventral colon mounted in Ussing chambers. In experiment 1, collection and
      incubation solutions were: control (no additions); flunixin meglumine, 4
      micrograms/ml; indomethacin, 10(-6) M; and flunixin meglumine (4 micrograms/ml)
      with 10(-6) M prostaglandin E2. In experiment 2, incubation conditions were:
      control [plain Krebs-Ringer bicarbonate [KRB] solution]; flunixin meglumine, 4
      micrograms/ml in KRB; chloride-free buffer solution; flunixin meglumine (4
      micrograms/ml) in a chloride-free buffer solution; and plain KRB with 10(-6) M
      prostaglandin E2. In experiment 3, tissue from 3 groups (n = 6 each) of animals:
      controls, physiologic saline solution given IV at 10 minutes before euthanasia;
      flunixin meglumine (1.1 mg/kg of body weight, IV) given at 10 minutes before
      euthanasia; and treatment similar to controls, except that tissues were incubated
      with 8 micrograms of flunixin meglumine/ml of bathing medium. RESULTS: Flunixin
      meglumine and indomethacin reduced Isc to approximately a third of control
      current (P < 0.05), but coincubation with flunixin meglumine and 10(-5) M
      prostaglandin E2 restored Isc close to the control value. Incubation with 10(-6)
      M prostaglandin E2 alone did not change Isc. When chloride was substituted with
      isethionate, flunixin meglumine had no effect on Isc. Flunixin meglumine given
      before euthanasia or included at a concentration of 8 micrograms/ml in all tissue
      preparation and incubation solutions reduced Isc (P < 0.05). CONCLUSIONS:
      Flunixin meglumine given IV or added to bathing solutions decreased Isc in equine
      right ventral colon by a mechanism that appeared to involve prostaglandin
      mediated chloride secretion. CLINICAL RELEVANCE: Our results suggest that
      flunixin meglumine given IV to horses at recommended doses could alter putative
      effects of colonic prostaglandins.

PMID- 9256982
TI  - Immunocytochemical localization of adrenocorticotropic hormone-immunoreactive
      cells of the pars intermedia in thoroughbreds.
AB  - OBJECTIVE: To analyze and characterize adenoma and hyperplasia of the pars
      intermedia (PI) of Thoroughbred mares. ANIMALS: 165 Thoroughbred mares, without
      clinical signs of hyperadrenocorticism that had been euthanatized or had died, of
      causes such as sudden death, colic, pneumonia, or trauma, and were necropsied.
      Five of those horses, 17 to 25 years old, had a large pituitary gland at
      necropsy. Eight mares, 5 to 15 years old with normal-size pituitary gland, were
      selected at random for comparison. PROCEDURE: A morphologic comparison of the
      pituitary gland between horses with and without tumors of the PI was conducted by
      use of immunocytochemistry and morphometry. RESULTS: In horses with normal
      pituitary gland, the PI was supplied by a vast capillary or sinusoidal plexus,
      which connected that in the pars distalis (PD) with that in the pars nervosa
      (PN). Cells of the PI stained slightly with ACTH antiserum, but some cells in the
      border region, which is contiguous to the PD, were strongly ACTH immunoreactive.
      At necrospy, horses with an enlarged pituitary gland also had adenoma of the
      pituitary gland involving the PI. Cells of the border region were hypertrophied
      and stained strongly with ACTH antiserum. The area and number of individual tumor
      cells of the border region of the PI of horses with adenoma were significantly
      increased, compared with those in horses with normal pituitary gland.
      CONCLUSIONS: Cells of the PI-PD border region may secrete substantial quantities
      of ACTH, owing to stimulation by corticotropin-releasing factor. Adenoma and
      hyperplasia of the PI in Thoroughbred mares may be associated with
      hyperadrenocorticism.

PMID- 9256983
TI  - Evaluation of the catabolic activity of cartilage by measurement of serum keratan
      sulfate concentration in foals.
AB  - OBJECTIVES: To determine keratan sulfate (KS) concentration in the serum of foals
      at the early stage of growing, and to evaluate the role of serum KS as a
      cartilage catabolic marker, comparing its values with the fluctuation of serum
      alkaline phosphatase (ALP) activity as a measurement of osteoblastic activity.
      ANIMALS: 12 foals with normal growth and 3 foals with joint abnormalities within
      18 months after birth. PROCEDURE: Measurement of KS concentration and ALP
      activity in serum and radiographic and physical examinations were done. RESULTS:
      In all foals, serum KS concentration was high from 1 week after birth to 3 months
      of age, while serum ALP decreased with aging. The value started to decrease
      rapidly from 3 to 5 months of age, then gradually reached adult values. During
      the first 3 months, KS concentration in male foals was significantly higher than
      that in female foals. In 3 foals which had joint problems, KS concentration was
      higher than that in normally growing foals at 1 week, and at 1, 2, and 3 months
      of age. CONCLUSIONS: Cartilage catabolic activity is higher in developing foals
      up to 3 months of age, suggesting that the immature joint at this time could be
      easily affected by any factor of loading. Moreover, though only 3 diseased foals
      were examined, higher serum KS concentration in these foals suggest that this
      variable might be a useful measure of joint diseases, even at an early stage of
      life in foals.

PMID- 9256984
TI  - Women and alcohol abuse in primary care. Identification and intervention.
AB  - Female problem drinkers are less likely than men to be identified in the primary
      care setting. The authors studied 24 adult women attending a general, internal
      medicine clinic to assess the efficiency of self-reports of alcohol consumption
      when compared with physician identification and other measures and the impact of
      a brief intervention on alcohol consumption. Despite the high rate of lifetime
      (79%) and current (67%) alcohol diagnoses, no patient was in alcohol treatment.
      Physician identification of alcohol problems was least sensitive but most
      specific, when compared with other measures. Brief intervention, as offered in
      this study, did not appear to modify alcohol consumption.

PMID- 9256985
TI  - Cost of comorbid alcohol and drug problems.
AB  - The authors measured the comorbid effect of alcohol and other drug (AOD) problems
      on medical, surgical, and psychiatric inpatient charges and length of stay (LOS)
      in an urban hospital by use of retrospective study of hospital clinical computer
      data comparing AOD-affected patients with non-AOD-affected patients in terms of
      cost, diagnostic, demographic, and utilization variables (N = 14,768). Patients
      were men and women with and without comorbid history of AOD problems, admitted
      for medical, surgical, and psychiatric reasons. For 10 of the 20 most frequent
      Diagnosis-Related Groups (DRGs), total hospital charges and LOS were
      significantly lower in patients with comorbid AOD problems (P < 0.001). Overall,
      for the most frequent 20 DRGs, total charges and LOS remained significantly lower
      for the AOD group. Most physicians believed that AOD-affected patients were often
      less ill than non-AOD patients within the same DRG. Alcohol/drug-affected
      patients had robustly lower costs and LOS. Fragmentation of psychosocial costs
      and addiction treatment from general health care and the fee-for-service DRG
      system appear to financially reward acute-care hospitals to repeatedly treat
      secondary AOD sequelae without providing any apparent incentives for the
      treatment of the primary alcohol/drug condition itself.

PMID- 9256986
TI  - Further evidence of an association between attention-deficit/hyperactivity
      disorder and cigarette smoking. Findings from a high-risk sample of siblings.
AB  - The authors investigated the relationship between attention-deficit/hyperactivity
      disorder (ADHD) and cigarette smoking in siblings of ADHD and non-ADHD probands.
      They conducted a 4-year follow-up of siblings from ADHD and control-group
      families. In the siblings of ADHD probands, ADHD was associated with higher rates
      and earlier onset of cigarette smoking. There was also a significant positive
      association between cigarette smoking and conduct disorder, major depression, and
      drug abuse in the siblings, even after adjusting for confounding variables.
      Moreover, smoking was found to be familial among ADHD families but not control
      group families. Our findings indicate that ADHD is a risk factor for early
      initiation of cigarette smoking in the high-risk siblings of ADHD probands.

PMID- 9256989
TI  - Predictors of successful vs. unsuccessful outcome of a 12-step inpatient alcohol
      rehabilitation program.
AB  - Comparison of successful vs. unsuccessful outcome at 1-year follow-up for 101
      patients treated in a VAMC inpatient alcohol rehabilitation unit, which used a
      combined 12-step facilitation/relapse prevention treatment model, revealed
      remarkably few predictors of outcome. However, one variable (self-reported
      absence of a mainstream Christian religious preference) strongly predicted poor
      outcome, whereas absence of a family history of alcoholism or a positive history
      of combat experience predicted a successful outcome. These results are among the
      first to examine the characteristics of patients who do well or poorly in this
      type of program and may, if replicated, begin to provide a basis on which to
      develop clinical algorithms for patient-treatment matching.

PMID- 9256987
TI  - Outpatient non-opioid detoxification for opioid withdrawal. Who is likely to
      benefit?
AB  - The authors examined characteristics of successful completers of an outpatient
      clonidine/oxazepam detoxification procedure for opioid dependence. Of 215 initial
      applicants, 167 received medication, and 65 successfully completed by taking a
      dose of naltrexone. Those who completed were more likely to have last used an
      opioid other than heroin, to be heroin smokers, rather than intravenous users, to
      have used benzodiazepines in the 30 days before treatment, and to have abstained
      from opioids for a longer time before presenting for treatment. New users (for
      less than 2 years) did no better than those using longer than 2 years. These
      findings may help in the continued refinement of patient placement criteria.

PMID- 9256988
TI  - Early prediction of initiation of abstinence from cocaine. Use of a craving
      questionnaire.
AB  - The authors administered a five-item craving questionnaire daily to 86
      outpatients to determine whether initial craving scores predicted the likelihood
      of initiation of abstinence within a 30-day period. Patients with higher mean
      craving scores during the first 3 days of the study were less likely to initiate
      abstinence. However the relationship between craving and abstinence initiation
      was not linear. Rather, patients in the top quartile of craving scores were
      significantly less likely to abstain than were patients in the lower three
      quartiles. The findings suggest that this rapid, easily administered craving
      questionnaire may have short-term predictive validity.

PMID- 9256990
TI  - Characteristics of smoked drug use among cocaine smokers.
AB  - The authors collected data by structured interview from a convenience sample of
      228 physically healthy, largely (82%) treatment-seeking, cocaine smokers with
      minimal histories of other smoked (other than tobacco and marijuana) or injection
      drug use. The vast majority of subjects also smoked either marijuana only
      (17.5%), tobacco only (17%), or both (61%), with onset of such smoking almost
      always (97%) preceding the initiation of regular cocaine smoking. There were few
      significant differences in sociodemographic or cocaine use characteristics among
      the subgroups of subjects smoking either cocaine only or cocaine and marijuana
      and/or tobacco. More than one-third of marijuana smokers quit (45%) or decreased
      (38%) their use after starting regular cocaine smoking, whereas only 5% of
      tobacco smokers did so. These findings suggest that marijuana smoking is more
      influenced by regular cocaine smoking than is tobacco smoking.

PMID- 9256991
TI  - The relationship of methadone dose and other variables to outcomes of methadone
      maintenance.
AB  - The authors evaluated the relationship of methadone dose to retention in
      treatment and to urine tests for morphine and cocaine in a cohort of 610 opioid
      users admitted to methadone maintenance and followed for 1 year. Methadone dosing
      was flexible, with patient participation in dose decisions. The maximum dose
      during treatment ranged from 10 mg to 110 mg, with a mean of 52 mg. Higher doses
      were associated with increased retention through the dose range of 60 mg-69 mg.
      Dose was not related to the likelihood of a positive morphine test but was
      related to the likelihood of a positive cocaine test. In this study, with
      flexible dosing and patient participation in dose decisions, patients were
      retained on methadone about as well as was reported in a previous study with
      patients on a fixed dose of 80 mg.

PMID- 9256992
TI  - A substance abuse consultation service. Enhancing the care of hospitalized
      substance abusers and providing training in addiction psychiatry.
AB  - The authors review the literature on the high prevalence but underrecognition of
      substance abuse among hospitalized patients and the general unavailability of
      hospital-based substance abuse consultation services. They describe the
      development, clinical operations, staffing, and teaching activities of a large
      substance abuse consultation service in one urban academic medical center and
      detail the service's growth and changing utilization patterns over an 8-year
      period, reporting the clinical characteristics of 1,819 patients seen over a 1
      year period. Differences in patient demographics, patterns of substance use, and
      diagnoses were highly significant from one referring service to another. The
      authors discuss the implications of such a service for patient care and teaching.

PMID- 9256993
TI  - Tolerability of naltrexone in treating older, alcohol-dependent patients.
AB  - The authors conducted an interim analysis of the tolerability of naltrexone among
      older, alcohol-dependent adults. Thirty-six subjects over 50 years old were
      enrolled in a 12-week, double blind, placebo-controlled efficacy study of
      naltrexone. Sixteen subjects received naltrexone and were compared with the
      placebo group for the development of adverse effects. Self-reported adverse
      effects did not differ in frequency or duration between the placebo and
      naltrexone groups. There were no significant differences in laboratory values
      between the two groups. Naltrexone was well tolerated with no clinically
      significant adverse effects. However, the efficacy of naltrexone has yet to be
      determined in this age group.

PMID- 9256994
TI  - Development of a new capillary electrophoresis-based fibre optic sensor.
AB  - A new fluorescence-based fibre optic sensor is described which combines the
      sensitivity offered by laser-induced fluorescence with the selectivity offered by
      capillary electrophoresis (CE). A single optical fibre directly probes the
      terminus of a 5-8 cm separation capillary. The linear geometry associated with
      this sensor necessitates a 'single reservoir' design, thus presenting major
      challenges to overcome in comparison to the conventional two-reservoir
      configuration common to a typical laboratory setup. Some of the challenges
      confronted by the design features presented in this work include the reduction of
      gravity-driven hydrostatic flow, the ejection of electrolytic gases evolved at
      the detection-side electrode and the establishment a suitable compromise between
      detectability and separation performance. The success of such design features
      demonstrates the feasibility of a CE-based sensor which offers several amenities
      particularly useful for in situ sensing. Such attributes include selectivity,
      diminutive size, flexibility, reusability, high sensitivity, speed, and remote
      control. Detailed descriptions of sensor fabrication are included, including two
      variations on a general design concept. In addition, the single-fibre optical
      detection system is described. Separation characteristics of the new CE-based
      sensor are presented, highlighted by an observed separation efficiency of up to
      8000 theoretical plates (for a 5 cm capillary). The separation of a three
      component mixture of the laser dyes, Rhodamine 6G, fluorescein isothyocyanate and
      sodium fluorescein, is demonstrated.

PMID- 9256995
TI  - Chiral separations of enantiomeric pharmaceuticals by capillary electrophoresis
      using sulphobutyl ether beta-cyclodextrin as isomer selector.
AB  - Capillary electrophoresis has developed into an extremely useful technique for
      the separation of optical isomers. High efficiencies and the availability of many
      types of isomer selectors allowing rapid and inexpensive methods development make
      capillary electrophoresis (CE) an attractive alternative to gas chromatography
      (GC) and high-pressure liquid chromatography (HPLC) for the determination of
      chiral purity. In this research the separation of the enantiomers of some chiral
      pharmaceuticals was investigated using anionic sulphobutyl ether-beta
      cyclodextrins as isomer selectors. These chiral selectors have a large
      countercurrent mobility, making them inherently advantageous as selectors as
      compared to neutral cyclodextrins. The effects of pH, buffer composition and
      selector concentration on the chiral separation of these compounds was
      investigated. All of the compounds studied were successfully resolved by the
      sulphobutyl ether beta-cyclodextrins (SBE-beta-CDs) typically with run times of
      less than 20 min using low concentrations of the SBE selector (1-5 mM).

PMID- 9256996
TI  - Measurement of total and bioactive interleukin-2 in tissue samples by
      immunoaffinity-receptor affinity chromatography.
AB  - The detection and measurement of cytokines is an important issue in the clinico
      pathological diagnosis of several clinical entities, including organ transplant
      rejection. Existing techniques, although sensitive, measure only total cytokine
      concentrations and cannot measure bioactivity. A chromatographic system combining
      immunoaffinity chromatography with an immobilized receptor detection cartridge
      has been developed for measuring total and bioactive interleukin (IL)-2
      concentrations in tissue extracts prepared from biopsy materials taken from renal
      transplant recipients during both rejection and drug-induced nephrotoxic
      episodes. The technique employs a short high-pressure chromatography column
      packed with antibody-coated glass beads for the initial analyte separation and
      concentration, followed by detection of bioactive molecules through their
      interactions with specific, immobilized receptors. This system compares
      favourably with both conventional bioassays and immunoassays for measuring IL-2
      in tissue samples.

PMID- 9256997
TI  - Detection of Aequorea victoria green fluorescent protein by capillary
      electrophoresis laser induced fluorescence detection.
AB  - Aequorea victoria green fluorescent protein was assayed by capillary
      electrophoresis using post-capillary laser-induced fluorescence detection in a
      sheath flow cuvette. The limit of detection was 3.0 x 10(-12) M protein in an
      injection volume of 17 nL, corresponding to a mass of 3100 molecules.

PMID- 9256999
TI  - Postcolumn chemiluminescence as a detection technique in the liquid
      chromatographic analysis of beta-lactam ring containing compounds.
AB  - A broad range of compounds containing the beta-lactam ring were screened for
      enhancement of luminol chemiluminescence. A selection of these compounds were
      found to enhance the chemiluminescence of luminol. A high-performance liquid
      chromatographic method for the analysis of some beta-lactams employing postcolumn
      chemiluminescence was developed via flow injection analysis studies.

PMID- 9256998
TI  - Size-selective derivatizations with polymer immobilized reagents.
AB  - A reagent immobilized on a macroporous polymer support was prepared for size
      selective derivatizations. These derivatization reagents showed two distinct
      reaction zones. Sterically bulky analytes were denied access to some of the
      surface of the support, so that when reagent on the outer surface was exhausted
      from the support, only analytes that had fail access to all regions of the
      support could react. These reagents were applied to the derivatization of
      different amines in the presence of a high concentration of a bulky analyte,
      adamantanamine. Pore size measurements and determination of molecular dimensions
      also support a size-selective derivatization mechanism. The reagents were also
      applied to the derivatization of proteins. Proteins with several sites available
      for tagging shows a reduced number of products with size selective reagents,
      reflecting reactions only at sites accessible to the reagent.

PMID- 9257000
TI  - Separation of chiral amino acids by micellular electrokinetic chromatography with
      derivatized cyclodextrins.
AB  - The chiral separation of several amino acid (AA) enantiomers derivatized with
      naphthalene-2,3-dialdehyde (NDA) was achieved by use of cyclodextrin-modified
      micellar electrokinetic chromatography (CD-MEKC). Both neutral hydroxypropyl beta
      cyclodextrin (HP-beta-CD) and charged carboxymethyl beta-cyclodextrin (CM-beta
      CD) were used as buffer additives for optical resolution of derivatized amino
      acids. The order of elution and the mechanism of separation for different CDs
      were explained by considering important chemical equilibria in the sodium dodecyl
      suphate, CD and amino acid system. Furthermore, the importance of SDS for the
      separation of a mixture of AAs, and the effect of CD and analyte concentration on
      the resolution will be discussed.

PMID- 9257001
TI  - Direct injection analysis of chlorzoxazone and its major metabolite 6
      hydroxychlorzoxazone in human serum using a semipermeable surface (SPS) HPLC
      column.
AB  - A semipermeable surface (SPS) HPLC column has been used to develop a direct
      injection method for the simultaneous determination of chlorzoxazone and its 6
      hydroxy metabolite in serum. Spiked serum was filtered and 20 microL injected
      directly onto the SPS column. The separation was achieved within 25 min using a
      mobile phase of 20:80 v/v acetonitrile-aqueous 0.05 M phosphate buffer pH 7 with
      detection at 230 nm. The method was linear in the concentration range 0.5-20
      micrograms/mL (r > 0.999, n = 6) with an RSD < 5%. The limits of quantitation and
      detection were 0.5 microgram/mL and 0.1 microgram/mL (S/N > 3), respectively, for
      both drug and metabolite. Intraday and interday reproducibility was < or = 6%
      with recoveries of drug and metabolite > 94%.

PMID- 9257002
TI  - Analysis of bile acids and bile alcohols in urine by capillary column liquid
      chromatography-mass spectrometry using fast atom bombardment or electrospray
      ionization and collision-induced dissociation.
AB  - Solid-phase extraction and group separation by anion exchange chromatography were
      combined with capillary column liquid chromatography-mass spectrometry (LC/MS) to
      permit a thorough characterization of bile acids and intact conjugates of bile
      alcohols in human urine. Groups of compounds were separated according to acid
      strength and were analysed on a capillary column, 0.25 x 500 mm, packed with 5
      microns particles of Chromasil C18, and connected via a fused silica capillary to
      the continuous-flow fast atom bombardment (CF-FAB) or electrospray (ES) sources
      of an AutoSpec-TOFFPD hybrid mass spectrometer. Acetonitrile:water mixtures
      containing 30 mM ammonium acetate pH 7.2 were used as mobile phases, with 5%
      glycerol added for FAB Ionisation. Bile acids were analysed directly or after
      derivatization of carboxyl groups with 4-aminobenzenesulphonic acid. Negative-ion
      spectra (m/z 1000 or 800 to 300 or 100) were recorded using the point detector
      or, in the case of ES ionization, the focal plane array detector (FPD).
      Deprotonated molecules of bile acids containing a sulphonic acid group were
      detected with a spectral signal to noise ratio of 5:1 when about 90 fmol were
      injected onto the column of the LC/CF-FAB system. The corresponding peak in the
      reconstructed ion chromatogram gave a signal-to-noise ratio of about 25:1. The
      sensitivity could be increased 20-50 times by using ES ionization and the FPD.
      Bile acids without a sulphonic acid group gave about 70% of the signal of
      sulphonic acids using ES ionization. The capillary column LC/MS systems were
      evaluated by analyses of urine from an infant with cholestatic liver disease.
      More than 150 different bile acids and bile alcohol conjugates were detected,
      some of which were partially characterized using collision induced dissociation
      (CID) of the deprotonated molecules and B/E linked scans. A number of compounds
      were detected for the first time, e.g. di-, tri-, and tetra-hydroxycholestanoic
      acids conjugated with N-acetylhexosamine and cholestenediol, cholestenetriol and
      cholestanetriol doubly conjugated with sulphuric acid and glucuronic acid. The
      relative merits of ES and FAB ionization are discussed.

PMID- 9257003
TI  - Asthma: a dynamic disease of inflammation and repair.
AB  - It is now widely accepted that asthma in its varied forms is an inflammatory
      disorder of the airways in which mediator release from activated mast cells and
      eosinophils plays a major role. T lymphocytes take a primary role in
      orchestrating these processes through their capacity to generate a range of
      cytokines of the interleukin 4 gene cluster encoded on the long arm of chromosome
      5. Additional cytokines derived from mast cells and eosinophils also play a key
      role, especially tumour necrosis factor alpha, which is responsible for
      initiating the up-regulation of vascular adhesion molecules involved in the
      recruitment of eosinophils and other inflammatory cells from the circulation. The
      importance of C-X-C and C-C chemokines as local chemoattractants and activating
      stimuli is also recognized. In addition to releasing an array of
      pharmacologically active autacoids, the inflammatory response in asthma results
      in the generation of proteolytic activities from mast cells (tryptase, chymase),
      eosinophils (MMP-9) and the epithelium itself (MMP-2, MMP-9), which exert tissue
      destructive and cell-signalling effects. The epithelium is also highly activated,
      as evidenced by the up-regulation of cytokine production, inducible enzymes and
      soluble mediators. Increased surface expression of the epithelial isoform of CD44
      (9v) and subepithelial proliferation of myofibroblasts are indicative of a
      simultaneous active repair process and the laying down of new interstitial
      collagens. Together, inflammatory and repair processes create the complex
      phenotype that characterizes asthma and its progression.

PMID- 9257004
TI  - Allergen recognition in the origin of asthma.
AB  - Allergic respiratory diseases such as bronchial asthma are believed to result
      directly from the repeated local expression in airway tissues of T helper (Th) 2
      polarized T cell immunity to inhaled allergens. Recent evidence suggests that
      these T cell responses are typically primed in utero and subsequently reshaped
      during postnatal allergen exposure via immune deviation, leading to the eventual
      emergence of stable allergen-specific T cell memory which is polarized towards
      the Th1 (normal) or Th2 (atopic) phenotype. The underlying Th1/Th2 switching
      process is influenced by a number of host and environmental factors that are
      poorly understood. Prominent amongst these are factors that affect the kinetics
      of maturation of immune competence during the early postnatal period. In
      particular, there is mounting evidence that the immunological milieu at the
      materno-fetal interface is naturally skewed towards the Th2 phenotype (possibly
      an evolutionary adaptation to protect the placenta against the toxic effects of
      Th1 cytokines). Furthermore, this bias appears to be preserved for varying
      periods into infancy, which may account for the presence of a high risk 'window'
      for allergic sensitization in early postnatal life. It is hypothesized that the
      principal impetus for postnatal development of a normal Th1/Th2 balance (and
      hence closure of the high risk sensitization window) is provided via contact with
      Th1-stimulatory commensal and pathogenic micro-organisms at the body's major
      mucosal surfaces.

PMID- 9257005
TI  - T cells as orchestrators of the asthmatic response.
AB  - The T cell hypothesis of asthma, particularly chronic asthma, is based around the
      concept that the disease is driven and maintained by the persistence of a
      specialized subset of chronically activated T memory cells sensitized against an
      array of allergenic, occupational or viral antigens which home to the lung after
      appropriate antigen exposure or viral infection. Allergens induce a CD4+ T helper
      (Th) cell response, whereas viruses recognize CD8+ T cytotoxic (Tc) cells. In the
      asthmatic airway there appears to be both CD4+ and CD8+ cells with a type 2
      cytokine phenotype (i.e. Th2 and Tc2 type). These cells produce: interleukin (IL)
      5, IL-3 and granulocyte macrophage colony-stimulating factor, which recruit,
      mobilize and activate eosinophils for subsequent mucosal tissue damage; and IL-4,
      an essential co-factor for local or generalized IgE production. This in turn
      leads to eosinophilic desquamative bronchitis, with epithelial shedding, mucus
      hypersecretion and bronchial smooth muscle contraction. Thus, although the
      eosinophil is largely responsible for airway symptoms, its function appears to be
      under T cell control. Support for this hypothesis includes: the observations that
      activated T cells and their products can be identified in biopsies from the major
      variants of the disease (atopic, nonatopic [intrinsic] and occupational asthma);
      the co-localization of mRNA for type 2 cytokines to CD4+ and CD8+ cells in atopic
      and non-atopic asthma; the presence of chronically activated cytokine-producing T
      cells in corticosteroid-resistant asthma; the association of disease severity
      with type 2 cytokines, especially IL-5; and the efficacy of cyclosporin A in
      chronic steroid-dependent disease. Inhibitors and/or antagonists directed against
      more precise T cell-associated molecular targets hold promise for the future
      treatment of chronic asthma.

PMID- 9257006
TI  - The structural and functional consequences of chronic allergic inflammation of
      the airways.
AB  - Although asthma is generally considered a form of reversible airway obstruction,
      there is evidence that chronic allergic inflammation can lead to structural
      changes in the airway and a degree of progressive fixed airway obstruction. More
      importantly, these structural changes can lead to airway hyper-responsiveness.
      The structural consequences of chronic allergic inflammation are secondary to
      cellular proliferation and reorganization of the connective tissue constituents
      of the airway wall. Smooth muscle proliferation and hypertrophy may increase the
      potential for smooth muscle shortening against the elastic loads provided by lung
      parenchymal recoil and airway mucosal folding. Resident airway cells, as well as
      inflammatory cells, produce mediators, cytokines and growth factors that
      stimulate production of connective tissue proteins and proteoglycans that cause
      airway remodelling and altered mechanical function. Thickening of the airway wall
      internal to the smooth muscle layer can amplify the effect of smooth muscle
      shortening on airway calibre, and it could also stiffen the airway making it less
      distensible. Thickening of the airway wall external to the muscle can uncouple
      the airway from the distending force applied by the lung parenchyma. Early and
      aggressive anti-inflammatory medication may alter the natural history of asthma
      by preventing the structural changes that are a consequence of chronic allergic
      inflammation.

PMID- 9257007
TI  - Genetic susceptibility to asthma in a changing environment.
AB  - There is a major interest in investigating the genetic components of allergy and
      asthma. Four different areas are involved in the study of complex genetic
      diseases: family studies, assessment of phenotype, segregation analysis and gene
      mapping. Initial assessment of phenotype must be practical, reproducible and
      relatively independent of compounding variables. Phenotypes important in allergy
      and asthma include atopic parameters such as total serum IgE, bronchial hyper
      responsiveness and the presence/ absence of clinical asthma. Numerous family and
      twin studies have suggested the presence of a heritable component for allergy,
      bronchial hyper-responsiveness and asthma. The number of genes involved in these
      complex genetic disorders and their mode of inheritance have not been fully
      determined. Our group has been involved in a collaborative US-Dutch study in
      which 92 families with over 500 individuals have been phenotyped and DNA has been
      obtained for genotyping. Initial results of the classification of family members
      show that approximately 26% of the offspring of families ascertained through a
      parent with asthma have an asthmatic phenotype. A large number of these offspring
      with clinical evidence of asthma do not have a prior physician diagnosis of
      asthma, suggesting that there is a spectrum which ranges from preclinical to
      symptomatic asthma. The familial aggregation of asthma and other obstructive
      airway diseases in these families is consistent with a significant genetic
      component. Initial linkage studies have been performed on two characteristics of
      the allergic and asthmatic phenotype. Total serum IgE was analysed because this
      measure correlates with the clinical expression of allergy, bronchial hyper
      responsiveness and asthma. Segregation analysis of total serum IgE provided
      evidence for a recessive mode of inheritance. Sib pair analyses and maximum
      likelihood scores suggest that a gene regulating IgE production maps to
      chromosome 5q. Bronchial hyper-responsiveness and total serum IgE are related to
      asthma in population-based studies. Sib pair analyses for bronchial
      responsiveness showed significant linkage to markers on chromosome 5q.

PMID- 9257008
TI  - Interpretation of epidemiological surveys of asthma.
AB  - Two particular issues make the interpretation of epidemiological studies in
      asthma problematic. The first is the lack of any clear definition of asthma. This
      is a perennial area of controversy. Thirty-eight years ago a Ciba Foundation
      guest symposium addressed this issue and suggested a solution. However, as J. G.
      Scadding, one of the participants of that symposium, pointed out after further
      consideration of the problem, what they had proposed was a description, not a
      definition. Since then, further attempts have been made but with little progress.
      They remain descriptive rather than definitive and have become, if anything,
      vaguer. The second problem has been the widespread failure to be precise about
      hypotheses or to define more precisely the hypothetical influences on asthma.
      Examples of this are the notions of 'inflammation' and 'atopy'. Standardization
      of methods for epidemiological studies of asthma is likely to provide a more
      rigorous framework for the comparison of results and the testing of hypotheses.
      Nevertheless, the development of such protocols should itself be seen as a
      hermeneutic device rather than an assertion of established knowledge.

PMID- 9257009
TI  - Evidence for the increase in asthma worldwide.
AB  - This chapter reviews the evidence that asthma is increasing and that changes in
      exposure to environmental risk factors may explain the increase. Although asthma
      is difficult to define for epidemiological studies, the prevalence of asthma as
      measured by the questionnaire definitions 'asthma ever diagnosed' and 'wheeze
      ever' is large and increasing. In all countries where serial studies using the
      same methods have been undertaken over the last 20 years, an increase in wheezing
      illness in children and adolescents has been recorded but there are insufficient
      data to determine whether the disease is increasing in adults. Despite the
      recorded increases, there remains a large difference in the prevalence of asthma
      between populations, with high rates of wheezing illness in Australasia and low
      rates in villages in poor countries. The male to female ratio for the occurrence
      of asthma remains at about 1.5 in children, 1.0 in late adolescence and less than
      1.0 in adults, when more females than males have symptoms. The risk factors for
      childhood asthma are atopy (positive skin tests), parental asthma, allergen load,
      respiratory infections, some aspects of diet and an 'affluence' factor. There is
      some evidence for an increase in the prevalence of atopy in children but this may
      be due to earlier acquisition of atopy. Changes in the other risk factors have
      not been documented. The evidence for changes in indoor allergen loads, in diet,
      in the severity and nature of respiratory infections, and in 'affluence' is
      indirect and comes from a number of small studies rather than from serial
      epidemiological studies. It seems unlikely that a single, environmental risk
      factor has changed dramatically worldwide. Rather, a number of lifestyle changes
      may have combined to cause the disease to be expressed in children who, in
      previous times, were immunologically protected from developing asthma, perhaps by
      their T helper cell phenotype, or were not exposed to high allergen levels.

PMID- 9257010
TI  - International trends in asthma mortality.
AB  - Throughout the 20th century many different patterns of asthma mortality have been
      observed. Following relatively stable asthma mortality rates during the first
      half of this century, there has been a gradual increase in asthma mortality in
      many countries over the last 50 years. Although a number of possible explanations
      have been proposed to explain this trend-including increases in asthma
      prevalence, increases in exposure to factors that trigger asthma attacks and
      changes in asthma management-their relative contribution in different countries
      is uncertain. Another pattern is that of sudden marked increases in asthma
      mortality occurring in at least seven countries in the 1960s and in New Zealand
      in the 1970s. Available evidence indicates that the cause of these 'epidemics'
      was the use of high dose preparations of two specific beta-agonist drugs, namely
      isoprenaline forte and fenoterol. The most recent trend observed in a number of
      western countries during the last decade has been a gradual reduction in asthma
      mortality; this may relate to improvements in the management of asthma.

PMID- 9257011
TI  - Inferences from occupational asthma.
AB  - Occupational asthma-asthma induced by an agent inhaled at work-provides a valid
      model for the examination of the more general environmental causes of asthma. In
      many instances, definable populations exposed to a novel allergen in the
      workplace at concentrations that are relatively easily measured develop IgE
      associated asthma and characteristic eosinophilic bronchitis. Carefully designed
      epidemiological studies suggest that the incidence of IgE antibody and asthma is
      highest in the first one to two years of exposure; and that the risk is directly
      related to the intensity of airborne allergen exposure. The relationship between
      exposure and outcome is modified both by concurrent cigarette smoking and by
      genotype, although the details of this latter interaction remain unclear.
      Symptoms, airway hyper-responsiveness and airway inflammation may persist for
      several years after avoidance of exposure to the initiating agent. If the
      relevance of the model is accepted then these insights require testing and
      further investigation, both within the field of occupational asthma and, by
      extension, in the wider field of asthma in the general environment.

PMID- 9257012
TI  - The role of domestic allergens.
AB  - The documented increase in asthma has been almost entirely in perennial asthma
      and a large proportion of the cases are allergic to one of the common allergens
      found all year round in houses, i.e. house dust mites, cats, dogs or cockroaches.
      In population and case-control studies sensitization to one of these allergens is
      the strongest risk factor for asthma (adjusted odds ratios > or = 4). Using
      monoclonal antibody-based assays for the major indoor allergens it has been shown
      that sensitization to house dust mites is directly related to the concentration
      of Group 1 mite allergen in dust. This led to the hypothesis that increases in
      mite allergen secondary to changes in houses were responsible for increases in
      asthma. However, asthma has also increased in areas of the world where mites do
      not flourish. In these dry areas sensitization to one of the other indoor
      allergens is the major risk factor for asthma. Although sensitization of
      asthmatics reflects the concentration of allergens in their houses, these
      measurements of exposure do not accurately predict severity of symptoms. Other
      factors that can contribute to the symptoms of asthma may also have increased. In
      particular, diesel particulates, ozone, beta 2-agonists, endotoxin and rhinovirus
      infection have each been shown to enhance the inflammatory response to inhaled
      allergens. Increases in asthma must relate to some aspect of our predominantly
      sedentary indoor lifestyle; this could be either increased exposure to allergens
      or an increase in factors that enhance the response of the lungs to foreign
      proteins.

PMID- 9257013
TI  - Air pollution and trends in asthma.
AB  - There is considerable concern about possible links between ambient air pollution
      and the upward trend in asthma. This chapter reviews the mechanistic and
      epidemiological evidence concerning air pollution and asthma and examines the
      hypothesis that trends in asthma could be explained by air pollution. It is
      concluded that existing evidence is not sufficient to link air pollution with the
      initiation of asthma in healthy subjects. Although there is better evidence that
      air pollution can provoke or aggravate asthma, it probably plays a minor role at
      a public health level, in comparison with other factors. It is therefore unlikely
      that trends in asthma could be explained by air pollution. Furthermore,
      correlations between some air pollutants and asthma over time are not consistent
      with the hypothesis. The possibility of a specific effect of motor vehicle
      pollution needs further investigation but this factor is unlikely to be the main
      cause of the worldwide increase in asthma.

PMID- 9257014
TI  - The role of respiratory viruses in asthma.
AB  - Respiratory infections are common causes of increased asthma for patients of all
      ages. Current evidence indicates that viral, and not bacterial, infections are
      the most important respiratory illnesses which increase the severity of asthma.
      Of the respiratory viral infections associated with increased asthma,
      rhinoviruses, i.e. the cause of common colds, have proven to be the virus most
      often found in association with increased asthma severity. Although the
      association between rhinovirus infections and asthma is most dramatically
      illustrated in children, asthma patients of all ages can be affected and the
      attacks of asthma can be severe. Studies to establish the mechanisms by which
      rhinoviruses enhance asthma severity have begun to focus on how this virus
      promotes allergic inflammation. We have found that experimental rhinovirus
      infections enhance airway responsiveness and, perhaps most importantly, the
      likelihood that a late allergic reaction will occur to an antigen challenge.
      Furthermore, using bronchoscopy and segmental antigen challenge, we have found
      that rhinovirus infections promote mast cell release of histamine and the
      recruitment of eosinophils to the airways. These data support the concept that
      rhinovirus infections act to promote allergic inflammation and by this mechanism
      increase both the likelihood of asthma occurring and the severity of wheezing.

PMID- 9257015
TI  - Prenatal origins of asthma and allergy.
AB  - The prevalence of asthma and related allergic disorders has increased
      considerably over the last 25 years. Genetic stock has not changed, so
      environmental factors must have influenced the phenotype. Infants who develop
      allergy already have an altered immune response at birth. We have investigated
      the development of immune responses during gestation and the effect of maternal
      allergen exposure during pregnancy and infant exposure in the first month of life
      on the development of allergy and disease. There was higher specific peripheral
      blood mononuclear cell proliferation to house dust mite (P = 0.01) and birch
      pollen (P = 0.004) in the third trimester compared with the second trimester,
      with the first positive responses seen at 22 weeks gestation. Maternal exposure
      to birch pollen after 22 weeks resulted in higher (P = 0.005) infant peripheral
      blood mononuclear cell responses to birch pollen at birth. Infants born at term,
      with at least one atopic, asthmatic parent, who developed allergic symptoms and
      positive skin prick test by one year of age had raised proliferative responses to
      house dust mites at birth compared to those with no symptoms (P = 0.01). In
      genetically predisposed individuals, antenatal factors, including maternal and
      thereby fetal exposure to allergens and maternoplacental-fetal immunological
      interactions, are active in determining whether an allergic predisposition is
      manifested as disease.

PMID- 9257016
TI  - Maternal risk factors in asthma.
AB  - There is now increasing evidence that maternal factors may play a role in the
      development of asthma and asthma-related syndromes in children. For years it has
      been known that younger mothers are more likely to have children who develop
      wheezing illnesses in early life. It has been suggested that the development of
      the lung may differ in children of younger mothers compared to that in children
      of older mothers, but the biology of this association is not well understood.
      Recent data suggest that there is a much stronger association of allergic
      conditions in early life with allergic disease in the mother than in the father.
      Maternal asthma is more strongly associated with childhood asthma than is
      paternal asthma. The influence of the pattern of immune responsiveness in the
      mother on the ontogeny of the immune system in children needs further
      exploration, and it may offer new clues as to the factors determining the
      development of asthma and allergy in children.

PMID- 9257017
TI  - Diet as a risk factor for asthma.
AB  - Asthma prevalence and morbidity have increased in the past 10 years in the face
      of improved knowledge about pathophysiology and treatment. Changing patterns and
      interactions among asthma risk factors may contribute to these disease trends.
      Diet is a newly recognized potential risk factor for asthma occurrence. This
      chapter focuses on the methodological issues in the assessment of diet as a risk
      factor for asthma and the available data linking diet to asthma, airway
      inflammation and airway responsiveness, and it concludes with a consideration of
      research needs and future directions. Four types of dietary constituents are
      considered: breast feeding and food avoidance in infancy; antioxidant vitamins,
      specifically vitamin C; dietary cations, specifically sodium and magnesium; and
      N3-N6 fatty acids. At present, available data are insufficient to implicate any
      dietary constituent as a causal risk factor for asthma. Data are strongest for
      vitamin C, which is associated with protective effects of airway responsiveness,
      lung function and asthma symptoms. Prospective cohort studies of the effects of
      early childhood diet on the development of asthma in children (birth to age six
      years) are needed to assess diet as a risk factor for early childhood asthma and
      its interrelationship with other risk factors.

PMID- 9257019
TI  - Location of alveolar clefts relative to the incisive fissure.
AB  - OBJECTIVE: The purpose of this study was to investigate, in a normal human fetal
      sample, the development of the anterior area of the palate. Emphasis has been
      placed on the bilateral epithelial fusion lines between the soft-tissue palatal
      shelves and the premaxillary mucosa, and on the relationship between these fusion
      lines and the locations of the inclusive fissures and of the tooth buds. The goal
      was to evaluate how the location of clefts in cleft lip and palate (CLP) patients
      interferes with tooth buds that are often affected in clefting. DESIGN: Nineteen
      maxillas of human fetuses underwent histologic examination after serial
      horizontal sectioning. Superimpositions of tracings from photographs of the
      histologic sections yielded information on the maxillary morphology at different
      levels. RESULTS: After elevation and fusion of the soft-tissue palatal shelves,
      the palatal fusions were Y-shaped. During subsequent osseous palate development,
      including formation of the incisive fissure and intermaxillary suture, the Y
      shaped epithelial fusions disintegrated. The locations of the anterior arms of
      the epithelial Y and of the incisive fissure did not coincide. CONCLUSIONS: The
      incisive fissure is likely not the location of clefts in CLP. The location of
      anterior palatal clefting in CLP patients follows the original course of the
      epithelial fusion between the palatal shelves and the premaxillary mucosa found
      in the region of the lateral incisors.

PMID- 9257018
TI  - Comparison of numeric techniques in the analysis of cleft palate dental arch form
      change.
AB  - OBJECTIVE: Quantitative descriptions of form (size and shape) changes are
      significant to the understanding of the development, treatment planning, and
      prognosis of patients born with cleft lip and palate. This study compared the
      results of traditional dental arch form change measurements, such as width,
      depth, perimeter, and area, with four numeric methods: finite element scaling
      analysis, macroelement method, Euclidean distance matrix analysis, and
      conventional least-squares and resistant-fit theta rho Procrustes analyses.
      DESIGN: Using tooth cusp landmarks on maxillary study casts, form change
      measurements of a male with complete bilateral cleft lip and palate at ages 2, 5,
      and 6 years were made comparing each age to the next older. RESULTS AND
      CONCLUSIONS: With the exception of the 2- to 5-year resistant-fit analysis, all
      numeric method: 1) provide comparable results, 2) provide more detailed
      descriptions than do traditional methods, and 3) provide results that correlate
      well with the reported effects of increased lip pressure due to lip closure
      surgery. The use of finite-element scaling analysis on study casts is somewhat
      limited since: 1) there is more than one solution at teeth shared by many finite
      elements, 2) gross averaging of form change occurs within triangular elements,
      and 3) solutions can vary with the choice of element location. The use of the
      macroelement method circumvented the above finite element limitations without
      compromising finite-element advantages. Procrustes results vary with the chosen
      superposition algorithm. The choice of the most appropriate Procrustes method
      required some a priori knowledge of form difference. The large number of results
      obtained by Euclidean distance matrix analysis and the nongraphic presentation of
      these results hamper quick interpretation but may be best suited for definitive
      statistical analysis. The graphic representation of both the magnitude and
      direction of: 1) landmark displacement in the Procrustes analyses (once size
      difference is eliminated), and 2) the rate of form change in the macroelement
      method provide an intuitive appreciation of how and where the casts differ.

PMID- 9257020
TI  - Maxillary growth following atelocollagen implantation on mucoperiosteal
      denudation of the palatal process in young rabbits: implications for clinical
      cleft palate repair.
AB  - OBJECTIVE: The implantation of atelocollagen matrix on the denuded surface of
      palatal bone following cleft palate repair has been used because it enhances
      wound healing. This study was performed to determine whether the beneficial
      effect of atelocollagen matrix implantation on the prevention of scar tissue
      contraction also inhibits the scar's interference with the growth of maxillary
      bone. METHOD: Fifty New Zealand White rabbits (aged 4 weeks) underwent palatal
      mucoperiosteal denudation, and etelocollagen matrix was implanted on the left
      palatal process. The opposite side was left open as a control. RESULTS:
      Histopathologically, the implantation side exhibited early infiltration of
      mononuclear cells and fibroblasts, and better growth of connective tissue strands
      and epithelium. In addition, the formation of rate ridges were seen that were
      similar to the normal mucosa. The bone of the atelocollagen-implanted side was
      covered with regenerated periosteum-like layers, but that of the control side was
      lined by granulation tissue, suggesting the existence of continuous inflammation
      on the periosteal region. When the animals reached adulthood (aged 24 weeks), the
      areas of scars and palatal processes, palatal shelf width, molar teeth incline,
      and bone mineral contents were measured and compared between sides. The
      atelocollagen-applied scars showed less contraction, the area and width of
      atelocollagen-implanted palatal processes showed more satisfactory growth, and
      the dental arch deformity was suppressed in comparison with the control side.
      CONCLUSIONS: Our results suggest that the use of atelocollagen matrix on the
      denuded bone surface following cleft palate repair decreases the scar's effect on
      maxillary growth.

PMID- 9257021
TI  - Three-dimensional study of growth and development of the nose.
AB  - OBJECTIVE: The aim of this study was to describe normal nasal growth in a large
      sample of boys and girls from 6 to 14 years of age, to compare nasal development
      at 14 years of age with its adult dimensions, and to evaluate differences in
      growth patterns between males and females. DESIGN: Growth and development of the
      nose were analyzed through the three-dimensional facial morphometry method. One
      thousand thirteen examinations were performed on 402 children between 6 and 14
      years of age and on 101 adults. Three-dimensional coordinates of five nasal
      landmarks were collected. Eleven parameters including nasal volume and external
      surface were calculated and averaged for age and sex. RESULTS: Volume, surface,
      and linear distances were larger in males than in females, with the exception of
      the 11-to-12 age group, where a sharp female growth spurt was present. In males,
      the growth spurt was broader, and continued to 13 years of age at a nearly steady
      rate. Statistically significant gender differences could be found both in the
      adult group and before the adolescent growth spurt. CONCLUSIONS: Our findings are
      in general agreement with previous reports on craniofacial growth, which
      suggested a strong tendency in males for growth to continue for several years
      beyond that seen in females.

PMID- 9257022
TI  - Application of thiamine in preventing malformations, specifically cleft alveolus
      and palate, during the intrauterine development of rats.
AB  - OBJECTIVE: Animal experiments were conducted to test the reproducibility of
      previously documented antiteratogenic effects of thiamine on cleft formation in
      the craniofacial system. DESIGN: Thirteen gravid Wistar rats carrying 98 fetuses
      were given the hydrazine derivative procarbacine (200 mg/kg BW) on the fourteenth
      day postconception (PC) to induce malformations, chiefly cleft alveolus and
      palate (day of determining presence of sperm was called the first day PC). Seven
      of the treated gravid rats carrying 48 fetuses were additionally given a daily
      dose of 200 mg/kg thiamine from the thirteenth to the nineteenth day PC. OUTCOME
      MEASURES: A comparative analysis of the fetuses in both experimental groups was
      conducted externally and, for the skeleton, macroscopically using special
      staining techniques; the heads were analyzed using successional histologic
      sections; bodies were examined stereomicroscopically using the razor-blade
      sectioning technique. RESULTS: In 12 of the 16 parameters evaluated, no
      statistically significant differences were found between experimental groups. In
      some cases, we even observed an amplifying effect of thiamine on the development
      of malformations in the rat strain used in our study. CONCLUSIONS: Because
      several previous authors have repeatedly described treatment with thiamine as one
      of the sufficient prophylactic measures in slowing the development of
      viscerocranial malformations, especially cleft alveolus and palate, it is of
      utmost importance that the timing of treatment and dosage of thiamine be taken
      into consideration not only in animal experiments but also when applying results
      to humans.

PMID- 9257023
TI  - Effects of fetus weight, dam strain, dam weight, and litter size on the
      craniofacial morphogenesis of CL/Fr mouse fetuses affected with cleft lip and
      palate.
AB  - OBJECTIVE: This study examined the factors related to the morphogenesis of the
      craniofacial complex of the CL/Fr mouse fetus affected with CLP based on the
      findings of a lateral cephalogram. DESIGN: Embryo transfer experiments were
      performed to determine the effect of the fetus weight, dam strain, dam weight,
      and litter size on the Intra-uterine craniofacial morphogenesis of CL/Fr mouse
      fetuses. On the 18th gestational day, each pregnant dam that had received CL/Fr
      mouse embryos was laparotomized to remove the transferred fetuses that had
      developed in the uteri of the cleft lip and palate (CLP)-susceptible CL/Fr strain
      dam and the CLP-resistant C57BL strain dam. A cephalometric observation of the
      craniofacial morphology of each fetus was subsequently performed. RESULTS: Based
      on a multiple regression analysis, the standardized partial regression
      coefficients of the affected fetus weight, the dam weight, and the litter size on
      the maxillary size of the affected CL/Fr fetus were 0.71 (p < .01), 0.03, and 
      0.07. According to a least-squares analysis of variance, the dam strain effect in
      addition to the effect of the affected fetus weight on the maxillary size and the
      cranial size of the affected fetuses was significant (p < .01 for cranial size, p
      < .05 for maxillary size) and close to a significant level (p = .09) for the
      mandibular size of the affected fetuses. The adjusted maxillary size and cranial
      size after statistically eliminating the effects of the affected fetus weight,
      dam weight, and litter size on each original craniofacial size of the affected
      fetuses that had developed in the CL/Fr dam strain were also significantly
      smaller than those of the affected fetuses that had developed in the C57BL dam
      strain. CONCLUSIONS: The present results indicate that the craniofacial growth of
      the CL/Fr mouse fetus affected with CLP increased in proportion to the fetus
      weight. The dam strain effect, in addition to the effect of the affected fetus
      weight, could thus not be ignored when the etiology of the spontaneous CLP was
      examined, while the uterine environment, provided by the CL/Fr strain dam,
      retarded the intra-uterine craniofacial growth of the affected fetuses. It was
      therefore concluded that the dam strain effect, as well as the effect of the
      affected fetus weight, both play an important role on the craniofacial
      morphogenesis of the CL/Fr strain of the affected fetuses that developed in both
      strain dams.

PMID- 9257025
TI  - Activities of superior pharyngeal constrictor and levator veli palatini muscles
      related to respiration in dogs.
AB  - OBJECTIVE: This study, using mongrel dogs, attempted to delineate the respiratory
      activity of two closure muscles of the velopharynx, the levator veli palatini
      (LVP) and superior pharyngeal constrictor (PC) muscles. METHOD: Fifteen mongrel
      dogs were given tracheotomies, with intratracheal tubes being connected to their
      respiratory circuits. Activities of the PC and LVP muscles were recorded
      electromyographically, and the effects of PaO2 and PaCO2 were analyzed along with
      the effects of lung inflation intratracheally with O2 and N2. RESULTS: Under
      hypoxic conditions, expiratory LVP activity was observed while PC activity
      diminished. The effects of lung inflation on both LVP and PC activities were also
      studied. The activities of both muscles were enhanced by lung inflation.
      CONCLUSION: It was thus suggested that the roles of both muscles during
      velopharyngeal closing movements are not the same.

PMID- 9257024
TI  - Elevated levels of transforming growth factors beta 2 and beta 3 in lambdoid
      sutures from children with persistent plagiocephaly.
AB  - OBJECTIVE: To analyze the pertinent history and physical findings specific to the
      subset of patients with a progressive posterior skull deformity, requiring
      surgery to correct their deformity. PATIENTS: Since the Academy of Pediatrics
      issued its recommendation on supine positioning of infants to prevent sudden
      infant death syndrome (SIDS) in 1992, 73 children have presented to the
      University of Virginia Craniofacial Anomalies Clinic with posterior-skull
      deformities. The majority were successfully managed with conservative therapy,
      but in six patients, the deformity was severe and persistent, requiring surgical
      correction. All six children were older (7.5-12 mo), presenting with more severe
      morphologic appearances and a higher incidence of associated neurodevelopmental
      delay. Three had family backgrounds of isolated craniosynostosis. METHODS:
      Characteristics of these patients were examined to determine why they may have
      differed from those that responded to conservative management.
      Immunohistochemical staining of their lambdoid sutures was performed. RESULTS:
      Significantly increased staining for TGF-beta 2 and TGF-beta 3, potent
      stimulators of bone cell growth and differentiation, was seen in all 'affected'
      sutures from the flattened side of the skull, compared to unaffected sutures from
      the protruding side of the skull-a pattern similar to that seen during normal
      bony obliteration of calvarial sutures. CONCLUSION: The majority of patients with
      posterior plagiocephaly associated with positioning responded to conservative
      management, while a small subset of patients with persistent posterior skull
      deformation required surgical intervention. A genetic basis for the latter
      patients' persistent plagiocephaly, rather than positioning, cannot be ruled out.
      Genetics, prolonged external pressure against the sutures, or a combination of
      these factors may lead to permanently raised levels of growth factors in
      'affected' sutures.

PMID- 9257026
TI  - Examine your orofacial cleft patients for Gorlin-Goltz syndrome.
AB  - The Gorlin-Goltz syndrome is characterized by four primary symptoms: multiple
      nevoid basal cell epitheliomas that usually undergo malignant transformation; jaw
      keratocysts that show constant growth; skeletal anomalies; and intracranial
      calcifications. A myriad of additional findings may also be noted. Among the most
      frequent are: palmar and plantar pits, a characteristic flattened facies and
      broad nasal root, frontal and parietal bossing, mandibular prognathia,
      hypertelorism, strabismus, dystrophia of the canthi, and clefts of the lip,
      alveolus, and/or palate. In this study, we review the literature and our 25 cases
      of Gorlin-Goltz syndrome patients, questioning their incidence of cleft
      formations (8.5%) as compared to the general population (0.1%). It is our
      contention that all patients who present with an orofacial cleft warrant deeper
      investigation as to the presence of additional signs indicative of Gorlin-Goltz
      syndrome. The nevi turn malignant with time, and thus, early diagnosis, follow
      up, and treatment are imperative.

PMID- 9257027
TI  - Breast feeding for cleft lip and palate patients, using the Hotz-type plate.
AB  - OBJECTIVE: Oral-cavity feeding movements were analyzed during sucking and used to
      modify a Hotz-type plate to facilitate sucking in infants with cleft lip and
      palate. DESIGN: Sucking movements were analyzed using lateral view cine
      radiography as three adults fed from a bottle. A Hotz-type plate was then
      modified to better isolate the oral cavity and to occlude the oral airway. The
      plate was then utilized in direct breast feeding by 10 babies. OUTCOME MEASURES:
      Sucking rate, amount of milk taken, and duration of use of the plate were
      assessed. RESULTS: Wearing this plate, four babies with cleft lip and palate
      could suck their mother's breast, drinking about 22 g/trial. CONCLUSIONS:
      Although supplemental bottle feeding was required to provide enough nourishment,
      this is the first step to reaching ideal breast feeding situation for these
      patients.

PMID- 9257029
TI  - The lambda flap for secondary cleft lip repair.
AB  - OBJECTIVE: A modified Abbe flap of the lambda figure type, designed by the author
      and used before or after secondary cleft lip repair in 146 consecutive cases
      since 1990 is described. DESIGN: This series consisted of 71 cases with
      unilateral deformity and 75 cases with bilateral deformity at adolescent or adult
      ages. The technical details of this method and representative cases with the
      results are shown. The philtrum is created by incising the two branches of the
      lambda flap obliquely at 45 degrees to the skin surface in the lower lip, then
      matching them in the central recipient bed of the deficient upper lip. RESULTS
      AND CONCLUSIONS: The resultant upper lip is not only full and slack, but also
      attractive with an acute cubic contour of the philtrum. Furthermore, the residual
      scar at the donor site is concealed in the mentolabial fold.

PMID- 9257028
TI  - Titanium mesh and bone dust calvarial patch during cranioplasty.
AB  - A technique of filling calvarial defects using bone dust reinforced with titanium
      Micro Mesh (Leibinger) was investigated using plain x-ray films and computed
      tomography (CT) in seven consecutive patients (age range, 7-21 years). The aim of
      our study was to assess whether, in the presence of the titanium, bone dust
      harvested with a power burr promotes persistent ossification that is comparable
      with adjacent bone. The mesh was localized by standard skull plain x-ray films,
      and orthogonal CT scans were obtained at between 9 and 18 months post
      operatively. An ultrahigh-resolution algorithm was used to detect neoossification
      on either side of the Micro Mesh (1-mm collimation, 330-mA and 120 KV(p) at the
      center of 400 HU, and window width of 2000 Hu). The mesh induced minimal streak
      artifact. Virtually no new bone formation was seen. It appears that bone dust was
      completely reabsorbed in this patient group even in the presence of semi-rigid
      fixation.

PMID- 9257030
TI  - The use of gingivoperiosteoplasty in CUCLP.

PMID- 9257031
TI  - Hallux limitus in the athlete.
AB  - Hallux limitus is one of the more common conditions occurring around the great
      toe, characterized by a progressive decrease in the dorsiflexion range of motion
      at the first metatarsophalangeal joint. Bony proliferation and articular
      degeneration of the joint result in pain and possible disability. Any force or
      condition which results in the restriction of dorsiflexion at the 1st
      metatarsophalangeal joint may, over time, produce typical changes around the
      metatarsophalangeal joint including the formation of dorsal exostosis, marginal
      osteophytes, erosion of articular cartilage and possible ankylosis. All of these
      changes are capable of producing pain in and around the joint. In summary, the
      condition is characterized by bony adaptations around the joint (hypertrophic
      spurring/ osteophytes, etc.) and eventual degeneration and destruction of the
      articular cartilage of the joint, possibly resulting in ankylosis. This article
      will review the biomechanical influences which may lead to hallux limitus/hallux
      rigidus, the clinical evaluation of the condition and suggestions for subsequent
      treatment.

PMID- 9257032
TI  - Angular surgical corrections for hallux valgus.
AB  - This article is an overview from a sports medicine podiatrist who deals mainly
      with athletes. The author addresses all aspects of rehabilitation.

PMID- 9257033
TI  - Achilles and peroneal tendon injuries in the athlete. An expert's perspective.
AB  - Peroneal tendonopathy or injuries are not common but may be troubling to the
      sports enthusiast. Prompt diagnosis and treatment usually result in complete
      recovery with conservative measures. Biodynamic orthosis with deep heel cups and
      a long lateral flange extension often are required for return to activity. MR
      imaging is helpful in difficult, persistent cases to check for ruptures. Surgery
      is not commonly performed but if required is usually successful in correcting the
      pathology. Alternative medicine may improve treatment outcomes. Biomechanical
      functional analysis and attention to training errors is essential in any lower
      extremity injury or pathology.

PMID- 9257034
TI  - Arthroscopic stabilization of the ankle.
AB  - Arthroscopic lateral ankle stabilization is a method for repair of the anterior
      talofibular ligament which involves decreased morbidity and minimal soft tissue
      disruption while restoring function and stability to the joint. This technique
      utilizes soft tissue anchoring systems that reinforce or repair the anterior
      talofibular ligament. Several techniques are described for the various types of
      ligamentous injuries. These methods are compared and contrasted with standard
      open reconstructive and reparative techniques. Advantages of the newer anchoring
      systems are discussed.

PMID- 9257035
TI  - Posterior tibial tendon dysfunction in the athlete.
AB  - It has been demonstrated that athletes who are properly diagnosed and treated
      early for PTT dysfunction with aggressive conservative management typically have
      a much better prognosis and are able to return to activities much sooner.
      Conservative management of this over-use or traumatic injury is helpful, even as
      a stop-gap measure in anticipation of a inevitable surgical correction. For the
      elderly, sedentary, or high-risk patient, aggressive conservative care is a
      viable option in lieu of surgical intervention. If surgery is indicated, however,
      there are a multitude of procedures to choose depending on the pathology and its
      extent.

PMID- 9257036
TI  - Management of Morton's neuroma in athletes.
AB  - The goal of the physician treating the athlete with Morton's neuroma should be
      the same as the goal of the athlete. This is to relieve the pain while allowing
      the athlete to continue with his or her activity as much as possible. Therefore,
      conservative therapy should be stressed. If it fails, all surgical methods,
      including the EDIN procedure, and their disadvantages should be considered before
      choosing to undertake one.

PMID- 9257037
TI  - Infracalcaneal heel pain in the athlete.
AB  - Heel-spur syndrome is a condition encountered on a daily basis by those
      practitioners who primarily treat athletes. The authors discuss anatomy, the
      clinical examination, radiographic evaluation, exercise, and alternative
      medicines.

PMID- 9257038
TI  - Dermatologic problems in podiatric sports medicine.
AB  - The podiatric physician should be keenly aware of various skin conditions and how
      to deal with them. Dermatologic conditions can be a significant deterrent to the
      athlete and his or her training schedule.

PMID- 9257039
TI  - Overuse foot and ankle injuries in ballet.
AB  - Incorrect techniques repeated daily by a dancer can lead to overuse injuries.
      This article discusses the causes and treatment of foot and ankle injuries in the
      ballet dancer. The author also addresses skin lesions that are common in dancers
      who wear pointe shoes.

PMID- 9257040
TI  - Rehabilitation of foot and ankle injuries.
AB  - Rehabilitation of foot and ankle injuries is essential for full functional
      recovery and prevention of chronic disease. Rehabilitation includes the usage of
      physical therapy modalities and rehabilitative exercise whose goals are the
      reduction of pain and edema and the increase of strength and proprioception.
      Physical therapy modalities may be classified as thermal, mechanical or
      electrical agents and include the use of ice, heat, ultrasound, phonophoresis,
      iontophoresis, intermittent compression, therapeutic massage and a variety of
      electrical currents. Rehabilitative exercises are primarily designed to increase
      flexibility, range of motion, strength, proprioception and sport-specific
      development prior to resumption of full activity. Proper rehabilitation of the
      lateral ankle (inversion) sprain is critical due to its frequency and potential
      for chronic pain and recurrence.

PMID- 9257041
TI  - Lower leg, foot, and ankle injuries in young athletes.
AB  - Most injuries to the young athlete do have a benign natural course-complete
      resolution of the difficulty without sequelae. In order to develop a contemporary
      program of management of the more serious disorders in this active population,
      the practitioner must be certain to carefully analyze the injury and initiate a
      rapid course of action. A fracture of the tibia must be reduced, held aligned,
      and then rehabilitated. A compartment syndrome commonly demands early fasciotomy;
      the young athlete and his or her parents warrant a sensitive understanding from
      physicians to quell the anxiety that is paramount to all of these disorders.

PMID- 9257042
TI  - Lipid abnormalities in progressive renal insufficiency.

PMID- 9257043
TI  - Hypertension, hyperlipidemia and microalbuminuria.

PMID- 9257044
TI  - Apolipoprotein E phenotype and renal disease.

PMID- 9257045
TI  - Lipoprotein glomerulopathy and its pathogenesis.

PMID- 9257046
TI  - Cholesterol as a predictor of progression in diabetic renal disease.

PMID- 9257047
TI  - Cholesterol as a predictor of progression in nondiabetic chronic renal disease.
AB  - In summary, then, there is an accumulating body of clinical human data supporting
      the concept that lipid nephrotoxicity may be important in the initiation of renal
      injury, and that lipids play a synergistic role in the inexorable process of
      progression to end-stage renal disease in nondiabetic as well as diabetic chronic
      renal disease. Further clarification of the role of lipid nephrotoxicity and
      impact of therapeutic interventions await data from larger prospective studies
      aimed at this specific question.

PMID- 9257048
TI  - Role of lipids in chronic renal allograft rejection.

PMID- 9257050
TI  - Treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes
      mellitus with progressive nephropathy.

PMID- 9257049
TI  - Effect of lipid-lowering therapy on the progression of renal disease in
      nondiabetic nephrotic patients.

PMID- 9257051
TI  - Effect of antiproteinuric treatment on the lipid profile in nondiabetic renal
      disease.

PMID- 9257052
TI  - The effect of HMG-CoA reductase inhibitors on chronic allograft rejection.

PMID- 9257054
TI  - Role of lipids in progressive renal disease: insights from the analbuminemic rat.

PMID- 9257053
TI  - Long-term low-density lipoprotein immunoapheresis in renal disease.

PMID- 9257055
TI  - Hyperlipidemia and tissue contents of N epsilon-(carboxymethyl)lysine in
      streptozotocin diabetes.

PMID- 9257056
TI  - Effect of lipids on glomerular fibrinolysis in vitro.

PMID- 9257057
TI  - Effects of lipoprotein (a) on mesangial cell biology.

PMID- 9257058
TI  - HMG-CoA reductase inhibitor suppression of glomerular cell proliferation in rats
      with anti-Thy-1.1 nephritis.

PMID- 9257059
TI  - The role of oxidatively modified lipoproteins in lipid nephropathy.

PMID- 9257060
TI  - Effect of low-density lipoproteins on mesangial cell expression of monocyte
      chemoattractant peptides.

PMID- 9257061
TI  - Regulation of mesangial cell proliferation by the mevalonate pathway.

PMID- 9257062
TI  - Hypercholesterolemia and progressive kidney disease: the role of macrophages and
      macrophage-derived products.

PMID- 9257063
TI  - Central role of the transcription factor nuclear factor-kappa B in mesangial cell
      production of chemokines.

PMID- 9257064
TI  - Isoprenoids, Ras and proliferative glomerular disease.

PMID- 9257065
TI  - Assessing quality of life in comparative cancer clinical trials: does it make a
      difference?

PMID- 9257066
TI  - Quality-adjusted survival analysis of malignant glioma patients.
AB  - The goal of therapeutic intervention in oncology patients is to prolong survival
      without compromising its quality. Definition and measurement of quality are quite
      difficult. This article discusses the statistical techniques for quantifying
      quality survival that have been used in brain tumor patients. These techniques
      assume either that all patients have equivalent baseline quality of life when
      both disease-related symptoms and toxicities are absent, or that the length of
      time with a predetermined level of impairment is equivalent to death. These
      models do not fit the heterogeneous symptoms experienced by patients with
      malignant brain tumors. We propose a model that incorporates the baseline states
      with transitions to different levels of severity that indicate improvement and/or
      declines in physical and cognitive functioning of brain tumor patients. The
      length of time spent in each state is observed and weighted by using
      predetermined utilities. The weighted time spent in each state is aggregated over
      all states into a quality-time of survival metric (QTIME). This QTIME model was
      applied to a previously published, randomized clinical trial of different
      radiation doses in malignant brain tumor patients.

PMID- 9257067
TI  - A longitudinal study of quality of life in advanced non-small cell lung cancer:
      Cancer and Leukemia Group B (CALGB) 8931.
AB  - A quality of life (QOL) endpoint supplemented standard clinical endpoints of
      survival, tumor response, and toxicity in a double-blind study conducted by the
      Cancer and Leukemia Group B (CALGB) where 291 patients with advanced non-small
      cell lung cancer (NSCLC) were randomly assigned to receive cisplatin/vinblastine
      with either hydrazine sulfate (HS) or placebo. The difficulties associated with
      the analysis of the longitudinal QOL data, and the contributions that the QOL
      endpoint made to the understanding of treatment differences, will be the focus of
      this paper.

PMID- 9257068
TI  - Assessing quality of life in comparative cancer clinical trials: does it make a
      difference?
AB  - Many randomized Phase III trials of cancer therapy involve quality of life
      assessments. This paper argues for graphical presentation of quality of life
      measures in order to visualize changes over time.

PMID- 9257069
TI  - Does assessment of quality of life in comparative cancer trials make a
      difference? A discussion.
AB  - This paper discusses two accompanying manuscripts addressing the question whether
      the assessment of quality of life in comparative cancer trials makes a
      difference. A number of thoughts and comments stimulated by the manuscripts are
      presented. It is concluded that, when comparing treatment regimens for a disease
      such as cancer, three measures can be considered in turn. First, the primary
      endpoint must remain: How long do patients survive? The logical next question is:
      How well do patients function? Then we have the third question: How well do
      patients feel? Certainly, these questions are interrelated, but our decisions
      will be the most rational (and we will provide the most useful information to
      patients) if we keep these distinctions in mind. Whatever the endpoint of
      interest, however, the appropriate way to compare different therapeutic
      interventions reliably is the randomized trial.

PMID- 9257070
TI  - Do quality of life assessments make a difference in the evaluation of cancer
      treatments?
AB  - The question posed by this set of quality of life papers is whether or not
      quality of life assessments in cancer clinical trials help evaluate the effects
      of cancer treatment on patient functioning. In this discussion, missing data
      problems, particularly those commonly found in advanced stage disease trials, are
      highlighted. Researchers are encouraged to investigate the extent of bias
      associated with missing data and to select analysis approaches accordingly. In
      the worst case, it may not be possible to analyze data longitudinally;
      descriptive or graphical portrayals of the data may be more appropriate. The
      importance of instrument reliability (minimizing measurement error) is emphasized
      for clinical trials research, particularly with respect to enhancing a trial's
      ability to detect quality of life differences by treatment arm. One strategy for
      addressing missing data is evaluated with respect to its impact on the
      measurement properties of the quality of life questionnaire. Clinical trials
      groups have been successful in obtaining quality of life data in multi-site
      settings and patients, by and large, appreciate the effort to include a
      systematic and standardized report of the effects of treatment on their
      functioning.

PMID- 9257071
TI  - An application of the Zucker-Wittes modified ratio estimate statistic in the Post
      Coronary Artery Bypass Graft (CABG) clinical trial.
AB  - In the Post Coronary Artery Bypass Graft (POST CABG) clinical trial, the primary
      outcome is substantial worsening (i.e., narrowing of the lumen diameter) of the
      vein grafts upon comparison of the baseline and follow-up angiograms. The
      patients had one to five non-occluded vein grafts at entry, so there may be from
      one to five primary outcome responses per patient. A modified ratio estimate
      (MRE) statistic, as described previously by Zucker and Wittes, may be used to
      analyze data of this kind. In the present paper we propose a more powerful MRE
      statistic when the event rates and/ or intraclass correlations vary according to
      number of grafts per patient. We also adapt this statistic to the factorial
      treatment design of the POST CABG clinical trial.

PMID- 9257072
TI  - Recruitment for controlled clinical trials: literature summary and annotated
      bibliography.
AB  - This article is a literature summary and annotated bibliography of research on
      recruitment for controlled clinical trials published through 1995. It extends and
      revises a similar review published in this journal a decade ago. The current
      commentary focuses on intervening developments in recruitment, including diverse
      populations, HIV trials, primary prevention trials, recruitment strategies,
      overall planning and management, patient and physician attitudes, adherence,
      generalizability, and cost. Profound barriers may exist in the recruitment of
      diverse populations, involving language, cultural factors, beliefs about medical
      research, and the appropriateness of available protocols. Extensive literature
      exists on patient and physician barriers to participation. Trials in HIV-infected
      or AIDs-diagnosed individuals introduce special considerations, including issues
      of confidentiality, parallel track design, and populations difficult to define
      and track. Recruitment strategies such as patient registries, occupational
      screening, direct mail, and the media are now prominent in the literature.
      Successful planning and management of an overall recruitment plan include
      piloting strategies, monitoring recruitment by data tracking systems, and hiring
      quality staff. Generalizability of study results is influenced by the
      characteristics of participants and by their adherence to study protocol. With
      increasingly limited funding to conduct clinical trials, efforts to quantify and
      reduce recruitment costs are being made. While over 4000 titles were identified,
      primarily by MEDLINE literature search, the articles summarized emphasize data
      supported and -confirmed conclusions, and broad coverage of disease areas. We
      annotate here 91 outstanding articles useful for formulation of overall
      recruitment approaches in clinical trials.

PMID- 9257074
TI  - Number of phones for telephone randomization.

PMID- 9257073
TI  - Design of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).
AB  - TOAST is a multicenter, randomized, placebo-controlled clinical trial testing the
      usefulness of a new antithrombotic drug in improving the outcome of persons with
      acute ischemic stroke. Until recently, no clinical trial testing a treatment for
      ischemic stroke had demonstrated efficacy in outcome. Design problems of
      previously conducted trials with inconclusive results may partly explain their
      failures. During the design of TOAST, the investigators addressed several issues
      so the trial could test the treatment accurately. We report the strategies used
      in designing, implementing, and coordinating the trial.

PMID- 9257075
TI  - The odds ratio.

PMID- 9257076
TI  - Imaging of facial trauma.
AB  - Severe facial fractures produce a variety of radiographic and CT abnormalities.
      Careful evaluation of plain films and any CT images should allow rapid and
      accurate diagnosis of the extent of injury. Table 3 summarizes the radiographic
      findings seen in the severe mid facial fractures.

PMID- 9257077
TI  - Computed tomographic evaluation of laryngotracheal trauma.

PMID- 9257078
TI  - An overview of the status of acellular pertussis vaccines in practice.
AB  - Infection with Bordetella pertussis continues to result in widespread morbidity
      and mortality. Although whole cell pertussis vaccines are effective in
      controlling pertussis, concerns relating to adverse effects following vaccination
      have led to the development of a new generation of pertussis vaccines. Acellular
      pertussis vaccines have decreased endotoxin content and are less reactogenic than
      whole cell vaccines. The composition of acellular pertussis vaccines varies,
      resulting in differing immunogenicity. Recent studies have demonstrated that
      these vaccines, in general, have an efficacy similar to that of whole cell
      vaccines. The development of acellular pertussis vaccines is an advance that
      should result in less discomfort from vaccination and the potential for increased
      vaccine usage, resulting in the possible elimination of this disease.

PMID- 9257081
TI  - A practical guide to the diagnosis and management of bone and joint infections.
AB  - Infectious arthritis arises from haematogenous spread of organisms through the
      synovial membrane or from the direct extension of a contiguous infection. The
      diagnosis rests on the isolation of the pathogen(s) from joint fluid obtained by
      aspiration or from debridement. Synovial fluid analysis and Gram stains provide
      clues to the aetiology. The treatment of septic arthritis includes appropriate
      antimicrobial therapy and joint drainage. Bone infections are currently
      classified by the Waldvogel or Cierny-Mader classification. Cierny-Mader staging
      allows stratification and development of comprehensive treatment guidelines for
      each stage. Osteomyelitis therapy emphasises early diagnosis and aggressive
      treatment. Radiographs and bone cultures are the mainstays of diagnosis.
      Radionuclide scans, computerised tomography or magnetic resonance imaging may be
      obtained when the diagnosis of osteomyelitis is equivocal or to help gauge the
      extent of the infection. Medical therapy includes improving any host
      deficiencies, initial antibiotic selection and antibiotic modification based on
      culture results. Surgical treatment involves debridement of necrotic bone and
      tissue, obtaining appropriate cultures, managing dead space and, when necessary,
      obtaining bone stability.

PMID- 9257080
TI  - Antiarrhythmic therapies for the prevention of sudden cardiac death.
AB  - Despite remarkable advances in cardiovascular therapeutics, sudden cardiac death
      remains a significant problem. In this review, data from clinical trials and
      other studies on antiarrhythmic therapies have been evaluated in order to
      determine effective strategies for the prevention of sudden cardiac death in high
      risk patients. Overall, routine prophylactic use of class I antiarrhythmic agents
      in high risk patients, mostly survivors of acute myocardial infarction, is
      associated with increased risk of death [61 trials, 23,486 patients: odds ratio
      (OR) 1.13; 95% confidence interval (CI) 1.01 to 1.27, p < 0.05]. Conversely, beta
      blockers are associated with highly significant reductions in risk of death in
      postinfarction patients (56 trials, 53,521 patients: OR 0.81; 95% CI 0.75 to
      0.87, p < 0.00001). Overall data from the amiodarone trials on high risk
      patients, including postinfarction patients, patients with congestive heart
      failure or survivors of cardiac arrest, suggest that this agent is effective in
      reducing the risk of death (14 trials, 5713 patients: OR 0.83; 95% CI 0.72 to
      0.95, p = 0.01) although further studies are needed to better define which types
      of patients will potentially benefit most from this agent. No benefits were seen
      with calcium channel blockers (26 trials, 21,644 patients: OR 1.03; 95% CI 0.94
      to 1.13, p = NS). The implantable cardioverter-defibrillator is a promising
      option for high risk patients, but definition of its role awaits the completion
      of ongoing clinical trials. Since causes of sudden death are heterogeneous, the
      clinician should pursue a multifactorial approach to its prevention. Primary and
      secondary prevention of cardiac ischaemia, through the treatment of
      cardiovascular risk factors and maximising the use of aspirin, beta-blockers,
      lipid-lowering drugs, and angiotensin converting enzyme inhibitors after acute
      myocardial infarction, should lead to a future decrease in the incidence of
      sudden cardiac death.

PMID- 9257082
TI  - Tacalcitol.
AB  - Tacalcitol is a vitamin D3 analogue which is available in Japan as a 2
      micrograms/g ointment for twice daily application and in Western markets as a 4
      micrograms/g ointment for once daily application. Tacalcitol inhibits
      proliferation, and induces the differentiation, of keratinocytes. In addition, it
      appears to modulate inflammatory and immunological mediators in the skin which
      may be involved in the aetiology of psoriasis. No significant systemic drug
      absorption occurs after application of tacalcitol to the skin. Results of
      clinical trials indicate that topical tacalcitol is effective in the management
      of stable plaque psoriasis (and possibly pustular forms of the disease), and has
      a similar efficacy to topical betamethasone valerate in this setting. Application
      of tacalcitol ointment 4 micrograms/g once daily for up to 8 weeks did not cause
      hypercalcaemia or hypercalciuria. Mild local skin irritation has been reported in
      a variable proportion of patients (< or = 12%).

PMID- 9257084
TI  - Valsartan. A review of its pharmacology and therapeutic use in essential
      hypertension.
AB  - Valsartan competitively and selectively inhibits the actions of angiotensin II at
      the AT1 receptor subtype which is responsible for most of the known effects of
      angiotensin II. In clinical trials in patients with mild to moderate essential
      hypertension valsartan was as effective as losartan, lisinopril, enalapril,
      amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure
      in patients who did not respond sufficiently to valsartan monotherapy.
      Preliminary data also suggest valsartan may be effective in patients with severe
      essential hypertension. The drug was as effective as lisinopril as treatment for
      mild to moderate essential hypertension in patients with renal insufficiency and
      did not worsen renal function. Headache, dizziness and fatigue were the most
      common adverse events in placebo-controlled studies; the incidence of these
      adverse events was not significantly different between placebo and valsartan
      recipients. Compared with ACE inhibitors, valsartan was associated with a
      significantly lower incidence of dry cough. Thus, valsartan is an effective
      treatment for mild to moderate essential hypertension and may be particularly
      useful in patients who experience persistent cough during ACE inhibitor therapy.

PMID- 9257083
TI  - Dolasetron. A review of its pharmacology and therapeutic potential in the
      management of nausea and vomiting induced by chemotherapy, radiotherapy or
      surgery.
AB  - Dolasetron (dolasetron mesilate) is a pseudopelletierine-derived 5-HT3 antagonist
      which has recently become available for clinical use. It is rapidly converted in
      vivo to its active major metabolite, hydrodolasetron, which appears to be largely
      responsible for its pharmacological activity. In clinical trials, single
      intravenous or oral doses of dolasetron were effective in preventing acute
      chemotherapy-induced nausea and vomiting (CINV). Intravenous doses of 1.8 mg/kg
      achieved complete suppression of vomiting in approximately 50% of patients
      receiving highly emetogenic cisplatin-containing chemotherapy and in
      approximately 60 to 80% of patients receiving moderately emetogenic chemotherapy.
      In the latter setting, oral doses of 200 mg achieved similar response rates. In
      comparative studies, intravenous dolasetron 1.8 mg/kg was as effective as
      intravenous granisetron 3 mg or ondansetron 32 mg after highly emetogenic
      chemotherapy, and oral dolasetron 200 mg was equivalent to multiple oral doses of
      ondansetron (3 or 4 doses of 8 mg) after moderately emetogenic chemotherapy.
      Dolasetron 1.8 mg/kg was superior to metoclopramide in preventing emesis induced
      by high dose cisplatin or by moderately emetogenic chemotherapy in high risk
      subgroups. Dolasetron has also shown efficacy in preventing radiotherapy-induced
      nausea and vomiting (RINV) in preliminary studies. Single intravenous or oral
      dolasetron doses ranging from 12.5 to 100 mg and 25 to 200 mg, respectively, were
      significantly more effective than placebo in preventing postoperative nausea and
      vomiting (PONV) in female surgical patients. A 50 mg intravenous dose was as
      effective in preventing PONV as ondansetron 4 mg in a mixed-gender group.
      Intravenously administered dolasetron was also effective in treating established
      PONV, although complete suppression of vomiting was achieved in < 40% of
      patients. Dolasetron has a tolerability profile characteristic of this class of
      compounds, with headache, dizziness and diarrhoea being the most commonly
      occurring adverse events in clinical trials. Diarrhoea is not thought to be
      related to dolasetron administration, being experienced mostly by patients
      receiving chemotherapy. Dolasetron and other 5-HT3 receptor antagonists have been
      associated with minor changes in ECG intervals, but these generally do not appear
      to be clinically important. Thus, available evidence suggests that dolasetron
      will provide an alternative to other 5-HT3 receptor antagonists for the
      management of CINV and PONV. Further studies are required to determine whether it
      offers any advantages over other agents in these settings and to determine the
      optimum dosage for preventing RINV.

PMID- 9257085
TI  - Ibutilide. A review of its pharmacological properties and clinical potential in
      the acute management of atrial flutter and fibrillation.
AB  - Ibutilide is the first 'pure' class III antiarrhythmic drug to become available.
      Its predominant action is prolongation of the myocardial action potential
      duration. This appears to be achieved by a unique ionic mechanism of action that
      involves activation of a late inward sodium current and possibly blockade of the
      rapidly activating component of the cardiac delayed rectifier potassium current.
      Intravenous ibutilide 0.01 to 0.025 mg/kg or 1 to 2 mg successfully converted
      atrial flutter or fibrillation to sinus rhythm in 33 to 49% of patients in 2
      placebo-controlled trials involving 439 patients with sustained arrhythmia. In a
      third trial in 300 patients who developed atrial flutter or fibrillation after
      cardiac surgery, ibutilide 2 mg successfully converted the arrhythmia in 57% of
      patients. The mean times to conversion were < or = 30 minutes in these trials. In
      3 comparative trials, ibutilide was significantly more effective than racemic
      sotalol or procainamide in terminating atrial flutter or fibrillation. The
      pretreatment duration of the arrhythmia is an important predictor of the success
      of ibutilide treatment; the greatest conversion rates are achieved when the
      arrhythmia is of recent onset (i.e. < or = 30 days' duration). Ibutilide is more
      effective in terminating atrial flutter than atrial fibrillation. Adverse events
      associated with ibutilide are predominantly cardiovascular. Sustained polymorphic
      ventricular tachycardia developed in 1.7%, and non-sustained polymorphic
      ventricular tachycardia in 2.7%, of 586 patients treated with ibutilide in
      clinical trials. However, no proarrhythmia-related deaths have been reported with
      the use of ibutilide. The drug has minimal haemodynamic effects and is associated
      with few noncardiovascular adverse events. Thus, ibutilide is a useful agent for
      the pharmacological cardioversion of recent-onset atrial fibrillation or flutter,
      provided that adequate steps are taken to monitor for proarrhythmic events. The
      drug causes few noncardiovascular adverse events and has minimal haemodynamic
      effects. Furthermore, it appears to be more effective than procainamide
      (especially in patients with atrial flutter) and racemic sotalol.

PMID- 9257088
TI  - Short-term trends in Dutch children's attention problems.
AB  - Changes in the prevalence of attention problems in Dutch children were examined
      by a comparison of prevalence rates in 1988 and 1993. On both occasions a
      representative sample of fourth-grade children from 82 regular elementary schools
      participated in the study. Both teacher reports and scores on an attention test
      indicated a small decrease in attention problems. We also found that the
      prevalence of other behavioral/emotional and reading problems had decreased or
      had remained unchanged. Subject to the limitations of the study, we concluded
      that the attention problems of fourth-grade Dutch children are not worsening.

PMID- 9257087
TI  - Prognosis in autism: do specialist treatments affect long-term outcome?
AB  - Many different treatments have been claimed to have a dramatic impact on children
      with autism. This paper reviews what is known about the outcome in adult life and
      examines the limitations and advantages of a variety of intervention approaches.
      It concludes that there is little evidence of any "cure" for autism, but
      appropriately structured programmes for education and management in the early
      years can play a significant role in enhancing functioning in later life.

PMID- 9257089
TI  - Depression among Swedish adolescents measured by the self-rating scale Center for
      Epidemiology Studies-Depression Child (CES-DC).
AB  - The self-report questionnaire Center for Epidemiological Studies-Depression Child
      (CES-DC) was used for screening depression in Swedish 16-17 year olds during
      their first year in high school. Completed questionnaires were produced by 2272
      students (92% of the population). The mean score was 13.2 (boys 9.9; girls 16.5).
      Factor analysis gave the same factors for boys and girls with a strong main
      factor for depressed mood. High scores of 30 or above were found in 240 cases
      (10.3%). Of those, 204 (85%) and the same number of controls with low scores were
      interviewed with the Diagnostic Interview for Children and Adolescents (DICA-R
      A). Depressive diagnosis during the last year was confirmed in 71% of high scores
      and 15% of low scorers. Beck's depression inventory with cut off at score 16 was
      used in the same material with equal result. Used with high cut off scores the
      CES-DC was specific enough for discovering depressive disorder.

PMID- 9257086
TI  - Salmeterol. A review of its pharmacological properties and clinical efficacy in
      the management of children with asthma.
AB  - Salmeterol xinafoate is a selective beta 2-adrenoceptor agonist indicated for the
      maintenance treatment of adults and children with asthma. When administered as a
      dry powder or aerosol, salmeterol produces bronchodilation for at least 12 hours
      and protects against methacholine and exercise-induced bronchoconstriction.
      Salmeterol is not recommended for the treatment of acute exacerbations of asthma.
      Recent clinical studies have demonstrated the efficacy and tolerability of
      inhaled salmeterol in the management of asthma in children. Salmeterol improved
      symptom control and lung function more effectively than placebo or regularly
      administered salbutamol. In children who were symptomatic despite regular inhaled
      corticosteroid therapy, the addition of salmeterol to treatment produced a
      significant improvement in morning and evening peak expiratory flow and forced
      expiratory volume in 1 second, and a significant reduction in the incidence of
      asthma exacerbations compared with placebo. Notably, the long duration of action
      of salmeterol makes it particularly suitable for the prevention of nocturnal
      asthma symptoms and exercise-induced asthma (EIA) in children. Current data
      suggest that salmeterol should not be used as a substitute for corticosteroid
      therapy in children, but rather as an adjunct to therapy. Thus, salmeterol may be
      a suitable adjunct to therapy in children with asthma receiving inhaled
      corticosteroids. In addition, salmeterol also has a potentially important role in
      the prevention of EIA and nocturnal asthma symptoms.

PMID- 9257090
TI  - Does oligoantigenic diet influence hyperactive/conduct-disordered children--a
      controlled trial.
AB  - A crossover 'placebo'-controlled, double-blind design was used to examine the
      effectiveness of an oligoantigenic diet in 49 children with
      hyperactive/disruptive behavior disorder. Effects of diet were compared with
      those yielded by stimulant medication (methylphenidate). The study was conducted
      in an inpatient unit at the Department of Child and Adolescent Psychiatry,
      Central Institute of Mental Health, Mannheim. Change in behavior was measured in
      standardized situations by trained raters, including behavior assessment when
      testing with CPT and PAT, during a free play situation, and at school. Twelve
      children (24%) showed significant behavioral improvement in two behavior ratings
      during diet relative to control diet conditions. Methylphenidate used in 36
      children yielded more responders (44%) than diet. The amount of positive changes
      in behavior in those who received both treatments was about the same. Although
      only effective in a minority of children, dietary treatment cannot be neglected
      as a possible access to treating hyperactive/disruptive children and merits
      further investigation.

PMID- 9257091
TI  - Behavioral aspects of infantile autism: an ethological description.
AB  - Eighteen children classified in four diagnostic groups--Infantile Autism, Full
      Syndrome Present (IA), Infantile Autism, Residual State (IA-R), Hyperkinetic
      Syndrome (HYPER), and Mental Retardation (MR)--were mutually compared on the
      basis of their behavior in a free child-adult interaction. An ethological
      analysis of 80 behavioral elements was performed, aiming at describing this
      interaction in detail. The analysis demonstrated that the autistic children with
      full syndrome present stayed closer to the adult and that they were more inclined
      to decrease the interpersonal distance than the children in the three other
      groups. Moreover, this group was often engaged in bodily contact with the adult.
      However, their facial orientation towards the adult was poorly developed, in fact
      they usually turned away their faces. Visual attention to the adult and
      manipulated objects was relatively low. Hand and head gestures were rare, but
      facial expressions occurred very frequently. Speech was seriously impaired, but
      probably counterbalanced by nonarticulated sounds. Finally, the adult seemed to
      have modified her behavior on a par with the child she was interacting with. From
      a behavioral point of view the autistic group with full syndrome present was
      clearly distinguishable from the three comparison groups, including the group
      with residual state autism.

PMID- 9257092
TI  - The family history of children with elective mutism: a research report.
AB  - The family history was studied in children with elective mutism. The samples
      comprised a series of N = 38 children with elective mutism and a control group of
      N = 31 children with a similar behavioural phenotype, i.e., the combination of an
      emotional disorder and a developmental disorder of articulation or expressive
      language. Interviews were performed with the respective mothers. There was a
      clear excess of the personality trait of taciturnity in first-, second-, and
      third-degree relatives. Although mutism was reported almost exclusively in the
      group of relatives of children that manifested elective mutism, the differences
      between the two samples were not significant probably due to low frequencies.
      Disorders of speech and language were quite common in the relatives of subjects
      in both samples. Psychiatric disorders were more frequently reported in the
      families with an electively mute child. The study lends some evidence for the
      assumption that genetic factors may play a role in the etiology of elective
      mutism.

PMID- 9257079
TI  - Diabetic nephropathy. Its relationship to hypertension and means of
      pharmacological intervention.
AB  - Hypertension and diabetes mellitus are common chronic conditions which frequently
      coexist. Diabetic nephropathy is a major cause of elevated blood pressure in
      patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy,
      arterial sclerosis, obesity and association of essential hypertension can be the
      causes of hypertension in patients with non-insulin-dependent diabetes mellitus
      (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal
      fall of blood pressure is blunted in patients with diabetic nephropathy. A
      blunted diurnal blood pressure variation is seen in microalbuminuric diabetic
      patients and even in some normoalbuminuric patients. Accumulating data suggest
      that normalisation of blood pressure in hypertensive IDDM patients is most
      important to minimise the loss of kidney function. Angiotensin converting enzyme
      (ACE) inhibitors have been reported to be effective in postponing the development
      of nephropathy and in slowing its progression. Whether only ACE inhibitors have
      such beneficial renal effects on diabetic nephropathy is under discussion. While
      many studies have suggested that insulin resistance and hyperinsulinaemia are
      related to an elevated blood pressure in hypertensive patients, there does not
      seem to be enough evidence to prove that insulin per se can raise blood pressure
      in humans. Neither an insulin infusion within a physiological range nor sustained
      hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic
      ovary syndrome) have been associated with an elevated blood pressure. Insulin
      resistance in some hypertensive patients may be a consequence of a decreased
      blood flow due to an increased peripheral resistance. Preliminary evidence
      suggests that low birth weight or impaired fetal growth is related to
      hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the
      contribution of genetic susceptibility and/or environmental inheritance. The
      frequent association of nephropathy with hypertension has led to research on the
      genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no
      reliable and clinically useful genetic marker has been found. Attempts to correct
      the metabolic abnormalities derived from diabetes are a new topic in the
      treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors
      (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the
      polyol pathway) and glycation inhibitors (inhibitors of formation of advanced
      glycosylation end-products) on diabetic nephropathy have been evaluated in animal
      studies and in some clinical trials. Thus far, results with HMG CoA reductase and
      aldose reductase inhibitors have been somewhat conflicting. The potential
      therapeutic role of glycation inhibition in the treatment of diabetes deserves
      further study.

PMID- 9257094
TI  - The status of child and adolescent psychiatry in EU- and EFTA-countries.

PMID- 9257093
TI  - Elective mutism and chromosome 18 abnormality.

PMID- 9257095
TI  - Modulators of nitric oxide in porcine endotoxemia: effects on hepatic oxygen
      delivery and consumption.
AB  - In a porcine model of endotoxemia we have studied the effects of nitric oxide
      (NO) on hepatic oxygen delivery and consumption. After 3 h of endotoxemia, NO
      biosynthesis was modulated by a bolus dose of the NO synthase inhibitor NG-nitro
      L-arginine methyl ester (L-NAME). Fifteen minutes thereafter a continuous
      infusion of the NO donor sodium nitroprusside (SNP) was started. Endotoxin
      significantly reduced hepatic oxygen delivery from 3.4 +/- 0.6 to 2.2 +/- 0.3
      ml/kg/min at 3 h. Due to an increased extraction ratio (ER), oxygen consumption
      was nearly unaffected. L-NAME further diminished oxygen delivery to 1.0 +/- 0.2
      ml/kg/min within 15 min (p < 0.05), but despite an increase in ER from 47 to 68%
      (p < 0.05), oxygen consumption tended to decrease (from 1.0 to 0.7 ml/ kg/min,
      nonsignificant). A similar tendency was observed in a control group of 9 pigs
      which was treated in the same way as the study group, except for the SNP
      infusion. SNP induced an almost selective increase in hepatic arterial flow, with
      a corresponding increase in oxygen delivery to 1.8 +/- 0.3 ml/kg/min (p < 0.05).
      At the same time ER was reduced from 68 to 42% (p < 0.05). Oxygen consumption
      remained unaltered. The control group exhibited no change in either oxygen
      delivery or consumption. The study shows that nonselective inhibition of NO
      synthesis is detrimental to hepatic perfusion and oxygen transport. The NO donor
      SNP increased oxygen delivery via a selective increase in hepatic arterial flow,
      but failed to influence oxygen consumption. This was probably mainly due to a
      massive shutdown of sinusoids, which did not reopen when flow was increased. A
      functioning microcirculation thus seems to be a prerequisite for the stimulation
      of organ blood flow to be effective.

PMID- 9257096
TI  - Assessment of intestinal integrity after ischemic preservation by luminal and
      vascular perfusion in vitro.
AB  - BACKGROUND: In the present study a technique for isolated perfusion of rat
      intestines in vitro should be tested as an evaluative tool in the assessment of
      intestinal alterations related to ischemia and reoxygenation. METHODS: Segments
      of upper jejunum (15 cm) were isolated from Wistar rats with vascular pedicle
      (superior mesenteric artery, SMA and portal vein). The SMA was cannulated with
      polyethylene tubing and flushed with 10 ml of University of Wisconsin (UW)
      preservation solution. The intestinal lumen was rinsed with 10-15 ml of UW
      solution and the organ was stored immersed in UW solution at 4 degrees C for 4 or
      18 h. After cold ischemic storage structural and functional integrity of the
      preparation was tested by biluminal perfusion with artificial buffer via SMA (5
      ml/min modified Krebs-Henseleit buffer, 200 mg% glucose, 5% dextran 78, 0.06 mg%
      dexamethasone, 7 mg% atropine to counteract paralytic hypersecretion) and the
      intestinal lumen (0.5 ml/min NaCl 0.9% with 200 mg% of galactose). The in vitro
      model was validated by perfusion of control preparations harvested without
      ischemic alteration. It was seen that ischemic preservation of 4 h had only a
      minor impact on the recovery of cellular ATP content and enzyme release (LDH)
      upon reperfusion, whereas both parameters were significantly changed after 18 h
      of preservation. Functional parameters like transmucosal carbohydrate absorption
      and luminal water balance, however, were significantly impaired already after 4 h
      of ischemic storage of the gut, thus yielding sensitive criteria for the
      appreciation of the postischemic integrity of the gut. CONCLUSIONS: It is
      concluded that the isolated gut preparation, being an inexpensive and technically
      feasible model, may be a useful tool in experimental research of intestinal
      ischemia/reperfusion.

PMID- 9257097
TI  - The functional and morphological damage of ischemic reperfused skeletal muscle.
AB  - Skeletal muscle is frequently damaged by ischemia-reperfusion both caused by
      direct injury and also by surgery. The purpose of the present experiments was to
      examine how the different types of skeletal muscles (fast and slow) react
      functionally and morphologically after 1 and 2 h of ischemia followed by
      different periods of reperfusion. The fast-twitch (musculus extensor digitorum
      longus, EDL) and the slow-twitch (musculus soleus, SOL) muscle of Wistar rats
      were prepared. They were stimulated in vivo, either directly or indirectly at
      different reperfusion times following tourniquet ischemia, and the contraction
      force of the muscles was recorded. The morphological changes were examined by
      light microscopy. At early reperfusion times, the contraction force of the EDL
      muscle was reduced by 40 and 90% after 1 and 2 h of ischemia, respectively. The
      contraction force was about 50% at the end of a 2-week reperfusion period in the
      1-hour ischemia group and it increased significantly (from 5 to 38%) during the
      second week if the ischemia lasted for 2 h. Reduction of contraction force in the
      SOL muscle was over 50 and 90% following 1 and 2 h of ischemia, respectively, and
      it started to improve from the 2nd week. Morphological changes of the two types
      of muscle were identical. At early reperfusion times granulocytes were seen in
      the blood vessels adhering to the endothelium. 24 h later neutrophil granulocytes
      migrated into the endomysium and thereafter into the perimysium. One week after 1
      h of ischemia both muscles showed normal histology. However, the structural
      regeneration process only started at the end of the 1st week of reperfusion after
      2 h of the ischemic damage. The following conclusions can be drawn. (1) There is
      functional morphological evidence of ischemic and reperfusion injury in both
      muscles after 24 h and also after 1 week of reperfusion. (2) Functionally, the
      two types of muscles regenerate differently, i.e. the SOL starts to regenerate
      earlier than the EDL. (3) Morphologically the two types of muscle show the same
      reactions. An increase in the time of ischemia from 1 to 2 h delays the
      regeneration processes.

PMID- 9257099
TI  - Prior ligation of portal branches improves survival after a 90% portal
      hepatectomy in the rat.
AB  - The ligation of portal branches is known to induce an atrophy of the deprived
      lobes and a hypertrophy of the nonligated lobes. In this work, we examined if
      this response occurs when the ligation affects 90% of the liver mass and if it is
      able to influence the survival rate after a hepatectomy of this magnitude. In
      male Wistar rats, major portal branches were ligated, keeping open only a small
      branch supplying the papillary lobes. The ligated lobes underwent a progressive
      weight loss and their DNA synthesis remained at the level of the controls. The
      nonligated lobes started to gain weight on the first postoperative day and had
      increased about 5-fold by the 14th day. The DNA synthesis in these lobes was
      greatly enhanced with a peak increase at 24 h. Two weeks after a similar ligation
      of portal branches, the ligated lobes, representing initially 90% of the liver
      mass, were resected and 80% of the rats survived. In the control group submitted
      only to a sham operation 2 weeks before, all rats died within 48 h after
      resection of the corresponding lobes. These results demonstrate that ligation of
      portal branches feeding 90% of the liver mass can be well tolerated and induces
      an atrophy of the ligated lobes and a hypertrophy of the nonligated lobes. This
      procedure, which improves the survival rate after an extended hepatectomy
      performed 2 weeks later, could find some clinical application.

PMID- 9257098
TI  - HTK versus UW solution for myocardial protection during moderate hypothermia.
AB  - The objective of this study was to assess the protective capacity of UW solution
      in comparison to Bretschneider's (HTK) cardioplegic solution under moderate
      hypothermic conditions (25 degrees C), as those usually present during
      intraoperative myocardial protection. Ischemia-induced alterations of cardiac
      function parameters were analyzed and compared for each solution after 45 min of
      ischemic storage and 60 min of reperfusion with oxygenated Krebs-Henseleit buffer
      (KHB), using a rat working-heart model. Compared to nonischemic values, left
      ventricular systolic and diastolic pressure, +dp/dtmax and -dp/dtmax were
      significantly better maintained in the HTK (95 mm Hg, 7 mm Hg, 2,657 mm Hg/s and
      2,122 mm Hg/s) than in the UW group (76 mm Hg, p < 0.05, 11 mm Hg, p < 0.05,
      1,745 mm Hg/s, p < 0.05 and 1,600 mm Hg/s, p < 0.05). Concerning the myocardial
      contents of ATP, creatine phosphate and the energy charge, a minor decrease was
      observed after preservation in HTK compared to UW solution. The results of this
      study indicate superior myocardial protection with the use of HTK solution for
      protection of the heart at 25 degrees C compared to UW solution.

PMID- 9257100
TI  - Changes in rat gastric mucosal glycoproteins in portal hypertension.
AB  - The aim of this study was to determine the effect of portal hypertension (PHT) on
      gastric mucosal glycoproteins in rats. PHT was induced experimentally by partial
      ligation of the portal vein (PVL) in 20 male Wistar rats: 10 rats (PVL4 group)
      were analyzed after 4 weeks and the remaining 10 (PVL8 group) after 8 weeks. In
      another group of 10 rats (control group), sham operations were performed. The
      severity of gastric mucosal lesions was evaluated macroscopically by a gross
      ulcer index. The gross ulcer indices in the PVL groups were significantly higher
      than those in the controls (p < 0.05). Histomorphometric evaluation of the
      intraepithelial mucin content, with the periodic acid-Schiff-Alcian blue staining
      technique, confirmed a significant decrease in mucosal glycoprotein production in
      the PVL groups (p < 0.05). Quantitative changes in gastric mucosal hexosamines
      were also used for mucosal glycoprotein analyses, and the hexosamine content of
      the gastric mucosa in the control, PVL4 and PVL8 groups were 300.7 +/- 7.8, 177.2
      +/- 4.9 and 169.1 +/- 3.5 micrograms/100 mg dried mucosa, respectively. The
      gastric mucosal hexosamine content was significantly lower in the PVL groups than
      in the control group (p < 0.05). No significant differences were observed between
      the two PVL groups in the above-studied parameters. These findings reveal that
      PHT causes a decrease in gastric mucosal glycoproteins in rats, and the decreased
      mucin content may weaken an important defensive factor of gastric mucosa. We
      suggest that gastric mucosal glycoproteins may play an important role in the
      pathogenesis of gastric mucosal lesions from PHT.

PMID- 9257101
TI  - Measurement of pancreatic blood flow to prevent pancreatic juice leakage after
      pancreas-preserving total gastrectomy for gastric cancer.
AB  - In patients with gastric cancer, distal pancreatectomy was frequently performed
      for complete removal of the lymph nodes along the splenic artery, but this
      procedure sometimes induced pancreatic juice leakage, subphrenic abscess, and
      postoperative diabetes. To avoid these complications, pancreas-preserving total
      gastrectomy (PP) was developed by Maruyama et al. [World J Surg 1995; 19:552
      536], with which the spleen, splenic artery, and fatty connective tissue
      including lymph nodes could be removed completely without distal pancreatectomy.
      From 1988 to 1995, 36 patients underwent PP in our department. Although there
      were no operative deaths and no patient developed postoperative diabetes,
      pancreatic juice leakage was observed in 4 patients (11.1%). We assumed that
      ischemia of the distal pancreas may have caused this pancreatic juice leakage and
      investigated the relationship between pancreatic blood flow (PBF) and this
      complication in 12 recent patients. A significant negative correlation between
      PBF in the pancreatic tail and the peak amylase level (PAL) in the drain fluid
      was demonstrated. Two patients with PBF values of 4.5 and 5.2 ml/min/100 g
      tissue, respectively, and a PAL of more than 2 x 10(5) U/l developed pancreatic
      juice leakage, whereas the 10 patients without this complication had PBF values
      above 6 ml/min/100 g tissue and a PAL of less than 2 x 10(4) U/l. These results
      suggest that measurement of PBF may be useful to predict the leakage of
      pancreatic juice after PP and that distal pancreatectomy may be preferable when
      PBF is extremely low.

PMID- 9257102
TI  - Processing of tumor tissues for vaccination with autologous tumor cells.
AB  - Vaccination with gene-transfected tumor cells has recently been proposed as a new
      strategy in the immunotherapy of cancer. Since autologous tumor cells provide an
      optimal antigen profile, the possibility of generating single cell suspensions
      from renal cell carcinoma (RCC), malignant melanoma (MM), colon carcinoma (CC),
      and non-small-cell lung cancer (NSCLC) biopsies was investigated. One hundred and
      seventy-four tumor biopsies were processed by mechanic and enzymatic
      dissociation, yielding 1-2 x 10(6) cells/g tumor (median), irrespective of tumor
      type. Primary tumor cell cultures (PTCC) of > or = 10(7) cells were established
      from 29 of 86 (34%) RCC, 14 of 38 (37%) MM, 11 of 23 (48%) NSCLC and 4 of 27
      (15%) CC specimens. The amount of non-tumor cells, as assessed by morphology and
      immunocytology, was generally low (< 30%) in RCC (35 of 41) and MM (11 of 17),
      while it exceeded 60% in 8 of 11 PTCC from NSCLC and 3 of 11 CC. A high tumor
      cell yield was obtained in biopsies with a high degree of vascularization and in
      the virtual absence of necrosis. Thus, PTCC > or = 10(7) cells were obtained in
      73% of MM with a high degree of vascularization and in 22% of MM with a low
      degree of vascularization (p < 0.007). Long-term tumor cell cultures exceeding 20
      passages were established in 24 of 86 (18%) RCC, 7 of 38 (18%) MM and 3 of 27
      (11%) CC, while successful implantation in nude mice was achieved in 8 of 20 RCC
      and 5 of 10 MM. Thus, under the conditions described, > or = 10(7) primary tumor
      cells of high purity could be generated from about one third of RCC and MM
      biopsies, while the success rate increased to > 50 and > 70%, respectively, in
      samples with a high degree of vascularization generated by an optimized biopsy
      technique excluding necrotic parts.

PMID- 9257103
TI  - Surgical treatment of early cancer of the proximal third of the stomach.
AB  - A retrospective study was conducted in search of an optimal surgical procedure
      for early cancer of the proximal stomach. The clinicopathological findings and
      survival data of 128 patients operated on during a recent period of 16 years were
      analyzed. Nodal metastasis was found in 12% of the patients and had a significant
      influence on the survival. It was more frequently observed in the
      undifferentiated type, regardless of the tumor size. Most metastases were found
      in the proximal paragastric nodes, and no metastasis was observed in the pyloric
      region or at the splenic hilum. These facts suggest that while the resection of
      paragastric nodes is advocated, neither total gastrectomy nor splenectomy is
      required simply for the purpose of lymphadenectomy.

PMID- 9257104
TI  - Octreotide acetate inhibits motility in the rabbit distal colon.
AB  - Octreotide, the long-acting somatostatin analogue, has been reported to modulate
      gastrointestinal motility in both animals and humans. A role in colonic
      peristalsis and a possible clinical application in common disorders, such as
      chronic constipation and irritable bowel syndrome, have not been evaluated. It
      has been previously suggested that octreotide promotes the descending relaxation
      of the peristaltic reflex arc. We hypothesized that this effect may involve
      inhibition of the motility index (MI) of the distal colon. To test this proposal,
      we studied peristalsis in isolated rabbit colons and also in the intact distal
      colons of anesthetized rabbits undergoing octreotide administration. Left colons
      of New Zealand white rabbits were harvested, placed in an isolated organ chamber
      and perfused with Krebs-Ringer bicarbonate solution via the inferior mesenteric
      artery. In a separate preparation, the colons were left in situ. Motility was
      quantified with a 6-port continuous infusion manometry catheter. The MI (mm
      Hg/min) was calculated by integration of the area of the digitalized signal
      (8/s), which reflected high-pressure peaks of different magnitudes. High-pressure
      waves were defined as > 20 mm Hg. Octreotide was infused via the inferior
      mesenteric artery in the isolated specimen or the lateral ear vein in the
      anesthetized animals in concentrations of 10(-12) to 10(-6) M. Octreotide
      inhibited high-pressure waves in a dose-dependent manner. These effects resulted
      in a decreased MI, with the maximum inhibition of 24.6% at 10(-11) M (p < 0.05 by
      ANOVA). At that concentration, the number of peaks > 20 mm Hg were reduced by
      62.2%. The data indicate that octreotide decreases the MI by inhibition of high
      pressure waves in the distal rabbit colon. These findings are consistent with the
      proposal that somatostatin may augment descending relaxation of the peristaltic
      reflex arc. This effect is independent of neural modulation.

PMID- 9257105
TI  - Intracellular trafficking of prohormones and proneuropeptides: cell type-specific
      sorting and targeting.

PMID- 9257106
TI  - Relationship between membrane potential, delayed rectifier K+ currents and
      hypoxia in rat pulmonary arterial myocytes.
AB  - Pulmonary arteries constrict in response to hypoxia, a process thought to involve
      oxygen sensing by K+ channels. We therefore investigated the effects of hypoxia
      on voltage-activated K+ currents in myocytes isolated from rat small pulmonary
      arteries using the patch-clamp recording technique. Experiments with iberiotoxin
      and intracellularly applied Ca2+ chelating agents revealed that hypoxia (PO2, 20
      30 mmHg; throughout) inhibited the Ca(2+)-insensitive component of the delayed
      voltage-activated outward K+ current. Hypoxia did not affect the membrane
      potential of these cells until they were depolarized by extracellular application
      of 20 mM K+, current injection or endothelin-1. Hypoxia caused little
      depolarization in the presence of prostaglandin F2 alpha, an agonist which was
      ineffective at inducing depolarization. These results suggest that an initial
      'priming' depolarization may confer a sensitivity to hypoxia by activating
      delayed rectifier (Kv) channels. Once active, these channels can then be closed
      by hypoxia, leading to further depolarization. It is unlikely, therefore, that Kv
      channels are involved in controlling the resting membrane potential of these
      cells.

PMID- 9257107
TI  - Gadolinium blocks the delayed rectifier potassium current in isolated guinea-pig
      ventricular myocytes.
AB  - The effect of Gd3+ on the delayed rectifier potassium current (IK) in single
      guinea-pig ventricular myocytes was tested using whole-cell patch-clamp
      techniques. It was found that Gd3+ blocked 70% of the IK tail current at a
      concentration of 100 microM. The EC50 was 24 microM. Action potential durations
      were, however, reduced, consistent with a predominant effect on depolarizing L
      type Ca2+ current (Ica.L). In the presence of 5 microM nifedipine Gd3+ prolonged
      the action potential. Using carbon fibres to stretch cells we observed that 10
      microM Gd3+ was not effective in reducing a large stretch-activated increase in
      resting calcium. Modelling studies using the OXSOFT HEART program suggest that
      this lack of response is influenced by blockade of repolarizing current but is
      best reproduced by additional blockade of Ca2+ extrusion via the Na(+)-Ca2+
      exchanger. When Gd3+ is used as a blocker of stretch-activated channels its
      actions upon both Ica.L and IK must therefore be accounted for.

PMID- 9257109
TI  - Inhibition of Ca2+ release in rat atrophied gastrocnemius muscle.
AB  - Contractile parameters of a twitch contraction and changes in these parameters
      during repetitive stimulation are modified by muscle atrophy induced by
      tetrodotoxin (TTX). These altered parameters included developed tension (DT),
      contraction time (tC), half-relaxation time (tR, 1/2), average rate of force
      development (DT tC-1) and peak rate of relaxation (DTdtmin-1). These
      modifications may be related to different Ca2+ concentration transients in the
      myoplasm during muscle stimulation. We have used dantrolene sodium (DS) in TTX
      treated rat gastrocnemius muscle to test this hypothesis. In situ isometric
      contractile responses of rat gastrocnemius muscle during repetitive stimulation
      at 10 Hz were analysed before and after administration of DS. After DS
      administration, twitch amplitude, tC, tR, 1/2 and DT tC-1 decreased and DTdtmin-1
      relative to DT increased in atrophied muscle. During repetitive stimulation, a
      progressive enhancement developed tension (staircase) was absent in atrophied
      muscle, but DT increased to 171 +/- 4%, presenting a staircase response after DS
      treatment. This potentiation was accompanied by an increase in DT tC-1 to 175.6
      +/- 7%. Inhibition of Ca2+ release in atrophied muscle resulted in twitch
      contractile parameters and contractile responses to 10 Hz stimulation that were
      similar, in many respects, to those responses in control (non-atrophied) muscles.

PMID- 9257108
TI  - Calcium paradox in guinea-pig ventricular myocytes.
AB  - Measurement of the release of lactate dehydrogenase (LDH), the development of
      contracture and the exclusion of the dye Trypan Blue were made in isolated guinea
      pig ventricular myocytes subjected to conditions that evoke a calcium paradox in
      intact heart. Incubation at 25 degrees C reduced the release of LDH associated
      with mechanical manipulation of the myocytes so that during prolonged incubation
      in media free of Ca2+ and Mg2+ ions at 25 degrees C little release of LDH
      occurred. A significant release of LDH into the incubation media was provoked on
      repletion of the divalent cations. This release was accompanied by a marked
      decrease in the percentage of rod-shaped myocytes and their ability to exclude
      Trypan Blue. The results provide evidence for the existence of the calcium
      paradox in isolated guinea-pig ventricular myocytes as originally defined.

PMID- 9257110
TI  - Ca2+ mobilization in cultured human bladder smooth muscle cells in response to
      hypotonic stimuli.
AB  - The effects of hypotonic solutions on intracellular Ca2+ were determined on
      primary cultures of human detrusor smooth muscle cells. In the presence of
      external Ca2+, changing from a solution containing 290 mosmol l-1 to one
      containing 240 mosmol l-1 (80% normal tonicity) activated a rise in intracellular
      Ca2+. If the exposure to 240 mosmol l-1 was followed by exposure to 150 mosmol l
      1 (50% normal tonicity) a further increase in Ca2+ was noted. Exposure to
      hypotonic solutions which contained nominally zero Ca2+ also resulted in a rise
      in intracellular Ca2+, suggesting that mechanical perturbation of the surface
      membrane can mobilize Ca2+ directly from intracellular stores. Stimulation of
      cells with a brief exposure to agonist (histamine, 5 microM) in the nominal
      absence of external Ca2+ produced a release of Ca2+ from intracellular stores.
      Under these conditions the response to a subsequent hypotonic stimulation was
      small or absent. These observations suggest that hypotonic stress induces a
      mobilization of Ca2+ from the same store as that activated by agonist. Detailed
      analysis of data from individual bladders revealed that there were significant
      differences between cells cultured from normal bladders and those from bladders
      with detrusor instability. On exposure to 240 mosmol l-1 cells from unstable
      bladders gave larger responses than cells from normal bladders. However, exposure
      of cells from unstable bladders to a subsequent stimulus of 150 mosmol l-1
      resulted in a smaller rise in Ca2+ than was observed with normal cells. Overall,
      these data suggest that isolated detrusor smooth muscle cells are sensitive to
      membrane stretch by hyposmotic solutions and that the mechanisms involved include
      the direct mobilization of intracellular Ca2+. The data also suggest that there
      may be differences in the responsiveness of cells isolated from stable and
      unstable bladders.

PMID- 9257111
TI  - Hyperbaric-induced enhancement of noradrenaline-evoked contraction in rat
      thoracic aorta.
AB  - The aim of this study was to investigate the effects of a high ambient pressure
      of He on vascular contraction induced by noradrenaline and to distinguish the
      effects of ambient pressure per se from those of increased pressure of inert gas.
      Rings of thoracic aorta were isolated from male Wistar rats. Isometric tension
      was measured in preparations exposed to 7.1 MPa (absolute pressure) of He. Dose
      response curves for noradrenaline and contractions elicited by 120 mM KCl were
      compared with time-matched experiments performed at atmospheric pressure. The
      same protocol was also carried out under 7.1 MPa of N2. At the high pressure of
      He, the contraction elicited by noradrenaline was increased with no change in the
      response to K(+)-evoked depolarization. The tension developed in response to
      noradrenaline also increased under 7.1 MPa of N2 but the effects were less marked
      than during the He experiments. Moreover, the response to KCl was reduced in this
      circumstance. Hyperbaric conditions enhance the noradrenaline-induced contraction
      of rat aorta in vitro. This effect probably results from an action of pressure
      per se on activation of adrenoceptors. However, the hyperbaric-induced increase
      in vascular smooth muscle contraction is partially counteracted by high pressures
      of inert gases (N2, but also probably He), which impair the efficiency of the
      contractile machinery.

PMID- 9257112
TI  - Secretory interactions between the sympathetic and parasympathetic innervations
      of the submandibular gland in the anaesthetized cat.
AB  - Interactions between the sympathetic and parasympathetic innervations of the
      submandibular gland have been investigated in the anaesthetized cat. At low
      frequencies of chorda lingual (parasympathetic) stimulation, simultaneous
      stimulation of the ascending cervical sympathetic nerve in bursts (20 Hz for 1 s
      at 10 s intervals) increased the flow of submandibular saliva, but the effect was
      never more than additive. The output of protein was consistently reduced by
      simultaneous stimulation of both the sympathetic and parasympathetic
      innervations, below that evoked by stimulation of either alone. Sympathetic
      stimulation was more effective than parasympathetic stimulation in promoting the
      secretion of tissue kallikrein and peroxidase in the submandibular saliva. The
      output of the latter enzyme, in response to sympathetic stimulation, was
      significantly reduced by simultaneous stimulation of the parasympathetic
      innervation at frequencies greater than 1 Hz, but nevertheless exceeded the
      amount secreted during chorda stimulation alone. Thus, this protocol provided no
      evidence of synergy between the two divisions of the autonomic nervous system
      with respect to any submandibular secretory function that was recorded. However,
      following the administration of a small dose of atropine (2-15 micrograms kg-1
      i.v.), sufficient to block secretion during chorda stimulation alone, the flow of
      saliva, in response to sympathetic stimulation, was potentiated when superimposed
      on a background of parasympathetic stimulation at all frequencies that were
      employed. This effect was abolished by larger doses of atropine, indicating that
      it was dependent upon activation of muscarinic receptors, only some of which
      could have been blocked by the initial dose.

PMID- 9257113
TI  - Cardiovascular and pancreatic endocrine responses to glucagon-like peptide-1(7
      36) amide in the conscious calf.
AB  - Intravenous infusions of glucagon-like peptide-1(7-36) amide (GLP-1; 35 pmol min
      1 kg-1 for 10 min) produced a significant rise in mean heart rate, without
      significant change in mean aortic blood pressure, together with a significant
      rise in mean arterial plasma insulin, but not in plasma pancreatic glucagon or
      pancreatic polypeptide concentration, in conscious calves given exogenous glucose
      (30-60 micromol min-1 kg-1 i.v.). The insulinotropic effect was eliminated in the
      presence of exogenous amino acids (0.03 mmol min-1 kg-1 i.v.). It was not
      affected predictably by blocking the synthesis of nitric oxide or by the
      simultaneous administration of the established incretin factor gastrin-releasing
      peptide (GRP). Whereas GLP-1 produced a statistically significant rise in plasma
      insulin concentration in these animals, it was much less effective than GRP in
      this respect, when given by continuous i.v. infusion.

PMID- 9257114
TI  - Pancreatic endocrine responses to the peptides VIP and PACAP in the conscious
      calf.
AB  - Pancreatic endocrine responses to vasoactive intestinal peptide (VIP), pituitary
      adenylate cyclase-activating peptide (PACAP) and acetylcholine have been
      investigated in conscious calves, while continuously monitoring aortic blood
      pressure and heart rate, in order to assess the effects of these neuropeptides
      under normal physiological conditions. VIP was found to modulate the release of
      pancreatic polypeptide (PP) in response to acetylcholine at a dose which had no
      significant effect on the release of either pancreatic glucagon or insulin. PACAP
      stimulated the release of insulin and the effect was potentiated during infusions
      of exogenous glucose. PACAP, when infused together with acetylcholine, also
      stimulated the release of pancreatic glucagon in the absence of exogenous glucose
      but not in its presence. Release of PP was stimulated during infusions of PACAP,
      whether or not exogenous glucose was given, and this effect was found to be
      additive with that of acetylcholine.

PMID- 9257116
TI  - Growth hormone does not affect non-insulin-mediated glucose uptake in sheep.
AB  - Four adult Merino sheep were used in the experiment, which was divided into four
      parts. For the 5 days before parts 1 and 3 saline was injected and for the 5 days
      before parts 2 and 4 growth hormone (GH; 4 mg day-1 subcutaneously) was injected.
      In parts 1 and 2 a primed continuous infusion of [6,6-2H2]glucose and either
      saline or GH, respectively, were infused for 5 h. The first 3 h was the control
      period. From 3 to 5 h insulin (0.5 mU kg-1 min-1) was infused. Coincident with
      the insulin infusion, normal glucose was also infused at a variable rate,
      dependent on the rapidly determined plasma glucose concentration, in order to
      keep the plasma glucose concentration constant. Parts 3 and 4 of the experiment
      were the same as parts 1 and 2, respectively, except for the following: the
      glucose isotope and saline or GH were infused for 7 h, from 3 to 7 h somatostatin
      (SRIF; 0.417 microgram kg-1 min-1) was infused, and from 5 to 7 h insulin was
      infused. Measurements of glucose turnover were made in the last 40 min of the
      control, insulin-only, SRIF-only and insulin-plus-SRIF infusion periods. Plasma
      insulin levels were reduced to below the level of detection by the SRIF infusion;
      under such conditions whole body glucose uptake should be entirely non-insulin
      mediated (NIMGU). Expressing glucose uptake as glucose metabolic clearance rate
      revealed that GH had no effect on NIMGU but significantly reduced the level of
      insulin-mediated glucose uptake (IMGU). Thus a reduction in the rate of NIMGU is
      probably not part of the mechanism by which GH repartitions glucose to sites of
      growth and milk production, whilst the present study confirms the antagonistic
      effect of GH on IMGU.

PMID- 9257115
TI  - An investigation into the relative merits of pituitary adenylate cyclase
      activating polypeptide (PACAP-27) and vasoactive intestinal polypeptide as vagal
      neuro-transmitters in exocrine pancreas of rats.
AB  - Pancreatic exocrine secretions were collected over 15 min periods and analysed in
      terms of weight of juice, total HCO3- and total protein in anaesthetized and
      pithed rats. Pituitary adenylate cyclase-activating polypeptide (PACAP) (i.v.)
      evoked a serous HCO3- secretion which contained relatively little protein,
      together with a marked vasodepressor action. The latter was still maximal at
      lower doses of PACAP, which evoked diminished pancreatic secretions. The effects
      of PACAP were similar to those evoked by the same dose of VIP and by cervical
      vagal stimulation, while secretion evoked a much larger secretion of fluid and
      HCO3-. The time courses of the PACAP-evoked secretions were significantly delayed
      compared with those of VIP. In the pithed rat, PACAP caused the same level of
      pancreatic secretions as in the anaesthetized rat, though this was now
      accompanied by a substantial pressor response which was blocked by phentolamine
      or prazosin, indicating that it was alpha 1-adrenoceptor mediated. VIP caused a
      depressor response in the pithed rat, as well as the same level of pancreatic
      secretions as in the anaesthetized rat. The putative VIP antagonist
      [Lys1,Pro25,Arg3,4,Tyr6]-VIP (abbreviated as VIPi) caused a selective and
      significant reduction in the HCO3- secretion evoked by VIP and blocked the
      vasodepressor response caused by VIP. By contrast, VIPi did not antagonize either
      the secretory or vasodepressor actions of PACAP. Unilateral electrical
      stimulation of the cervical vagus nerve evoked significant increases in the
      weight of juice, total protein and total HCO3- secreted. When preceded by
      injection of VIPi, vagally evoked secretions were unchanged in terms of weight of
      juice and total protein but had a significantly reduced HCO3- content. These
      results are consistent with the release of VIP, though not PACAP, as a vagal
      neurotransmitter in the exocrine pancreas.

PMID- 9257118
TI  - Fetal and maternal fluid balance in sheep during hyperthermia with and without
      water deprivation.
AB  - Our aim was to determine the effect of maternal hyperthermia, both with and
      without maternal water deprivation, on fetal fluid balance. Seven pregnant ewes
      (131.8 +/- 1.0 days gestation) were studied during a control period and periods
      of maternal heating (MH, 42-44 degrees C for 8 h, water freely available),
      maternal water deprivation (MWD, 30 h) and maternal heating combined with water
      deprivation (MH + MWD, 30 h deprivation with heating during last 8 h). Relative
      to control values, MH increased maternal water intake and urine output, and [K+]
      in fetal plasma and fetal urine. Relative to control values, MH decreased
      maternal plasma osmolality, [Na+] and [K+]; fetal plasma osmolality and [Na+];
      fetal lung liquid [Na+] and [Cl-]; and fetal production rates of lung liquid and
      urine. In response to MH + MWD, the osmolality, [Na+] and [Cl-] of maternal and
      fetal plasma, fetal lung liquid and fetal urine (excluding urinary [Cl-])
      increased compared with control values. In the fetus, MH + MWD increased plasma
      and urinary [K+], and decreased production rates of lung liquid and urine
      compared with control values. During MH + MWD, compared with MH alone, greater
      alterations were seen in maternal rectal temperature, water input and urine
      output; osmolality, [Na+] and [Cl-] of maternal and fetal plasma, fetal lung
      liquid and fetal urine (excluding urinary [Cl-]); and fetal urinary [K+]. During
      MH + MWD, compared with MWD alone, greater alterations were seen in maternal
      plasma [Cl-] and [K+]; fetal urinary osmolality and [K+]; and fetal plasma [K+].
      Our results show that, when water is available, maternal hyperthermia stimulates
      ewes to drink substantially more than under normal conditions, thereby decreasing
      their plasma osmolality; water transfer to the fetus may increase, thereby
      decreasing fetal plasma osmolality. When drinking water is unavailable, maternal
      hyperthermia and associated dehydration may decrease water transfer to the fetus.
      Thus, the fetus becomes not only hyperthermic, but also hyperosmotic and possibly
      hypovolaemic. Maternal hyperthermia, irrespective of the availability of drinking
      water, decreases production rates of lung liquid and urine in the fetus.

PMID- 9257117
TI  - Changes in the maternal and fetal renin-angiotensin systems in response to
      angiotensin II type 1 receptor blockade and angiotensin-converting enzyme
      inhibition in pregnant sheep during late gestation.
AB  - The effects of maternal administration of either an angiotensin II type 1 (AT1)
      receptor antagonist (GR138950) or an angiotensin-converting enzyme (ACE)
      inhibitor (captopril) on the renin-angiotensin system (RAS) were investigated in
      chronically catheterized ewes and their fetuses during late gestation. From 127
      +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received
      daily i.v. injections of GR138950 (3 mg kg-1, n = 10 animals) or captopril (3 mg
      kg-1, n = 6) or an equivalent volume of vehicle solution (0.9% NaCl, n = 10). On
      the first day of treatment, plasma renin concentrations in the pregnant ewe
      increased within 2 h of administration of either GR138950 (median change followed
      by lower and upper quartiles (25%, 75%): +38.3 ng ml-1 h-1 (15.6, 80.7); P <
      0.05) or captopril (+22.1 ng ml-1 h-1 (19.2, 28.8); P < 0.05). Maternal plasma
      concentrations of angiotensin II (AII) also increased by 871 pg ml-1 (555, 1340;
      P < 0.05) in the GR138950-treated ewes. In the fetuses of both groups of drug
      treated animals, an increase in plasma renin concentration was observed within 2
      h of maternal treatment with either GR138950 (+11.6 ng ml-1 h-1 (1.2, 18.6); P <
      0.05) or captopril (+59.3 ng ml-1 h-1 (41.7, 74.6); P < 0.05). These short-term
      changes in circulating renin and AII concentrations observed in the pregnant ewe
      were sustained after 1 week of GR138950 administration. In addition, 1 week of
      GR138950 treatment decreased plasma angiotensinogen (Ao) concentrations in both
      the ewe (-0.36 microgram ml-1 (-0.58, -0.16); P < 0.05) and the fetus (-0.43
      microgram ml-1 (-0.59, -0.09); P < 0.05). A long-term reduction in maternal
      plasma AII, and an increase in fetal plasma renin concentration, were associated
      with 1 week of captopril administration. Neither drug had any consistent effect
      on plasma ACTH or cortisol concentrations in the pregnant ewe or fetus. These
      findings show that, during ovine pregnancy, antagonism of maternal AII activity,
      either by blockade of the AT1 receptor or by inhibition of AII synthesis, induces
      changes in the circulating components of the RAS in the mother and fetus. In both
      the pregnant ewe and fetus, the RAS is shown to be activated by suppression of
      AII activity.

PMID- 9257119
TI  - Effects of 8h of eucapnic and poikilocapnic hypoxia on middle cerebral artery
      velocity and heart rate in humans.
AB  - This study examines the effects of prolonged hypoxia, with and without control of
      end-tidal CO2 partial pressure (PET,CO2), on the intensity-weighted mean velocity
      of blood flow in the middle cerebral artery (VIWM) and on heart rate (HR).
      Specifically, the time course of the responses, their reversibility with brief
      periods of hyperoxia and the recovery phase following prolonged hypoxia were all
      investigated. Twelve subjects were studied, of whom nine provided satisfactory
      data. A purpose-built chamber was used for the prolonged control of the end-tidal
      gases, and an end-tidal forcing system was used for generating the brief
      variations in end-tidal gases. Three 16 h protocols were employed: (1) 8 h
      eucapnic (average PET,CO2 = 39 mmHg) hypoxia (end-tidal O2 partial pressure,
      PET,O2 = 55 mmHg) followed by 8 h eucapnic euoxia (PET,O2 = 100 mmHg); (2) 8 h
      poikilocapnic (average PET,CO2 4 mmHg below eucapnia) hypoxia (PET,O2 = 55 mmHg)
      followed by 8 h poikilocapnic euoxia (PET,O2 = 100 mmHg); and (3) control (air
      inspired throughout). VIWM (using Doppler ultrasound) and HR were measured during
      brief exposures to hypoxic/euoxic and hyperoxic conditions with PET,CO2 held 1-2
      mmHg above eucapnia, at 0, 20, 240 and 480 min in the first 8 h, and at the same
      times in the second 8 h. There were no significant trends in VIWM under hypoxic
      conditions for either hypoxic protocol (ANOVA) and no significant differences
      between the three protocols for VIWM in hyperoxia (ANOVA). In contrast to VIWM,
      there was a significant increase in HR over time during both hypoxic exposures (P
      < 0.01, ANOVA). HR increased to a similar extent for the two types of hypoxia,
      and there was some suggestion that HR remained elevated after the relief of
      hypoxia. The results suggest that, with the level of hypoxia employed,
      progressive changes in HR occur, but that this level and duration of hypoxia has
      little sustained effect on VIWM.

PMID- 9257120
TI  - Street foods. Report of an FAO technical meeting. Calcutta, India. 6-9 November
      1995. United Nations.

PMID- 9257122
TI  - Identification of hydrogen peroxide oxidation sites of alpha A- and alpha B
      crystallins.
AB  - The alpha-crystallins are the most abundant structural proteins of the lens and,
      because of their chaperone activity, contribute to the solubility of the other
      crystallins. With aging, the lens crystallins undergo a variety of modifications
      which correlate with a loss of solubility and the development of cataract. A
      recent study demonstrating that alpha-crystallins exposed in vitro to FeCl3 and
      H2O2 exhibit decreased chaperone activity, implicates metal catalyzed oxidations
      of alpha-crystallins in this loss of solubility. The present study has determined
      that alpha-crystallins incubated with FeCl3 and H2O2 are modified by the nearly
      complete oxidation of all methionine residues to methionine sulfoxide, with no
      other detectable reaction products. The modifications were identified from the
      molecular weights of peptides formed by enzymatic digestion of the alpha
      crystallins and located by tandem mass spectrometric analysis of the
      fragmentation pattern of the mass spectra of the fragments from peptides with
      oxidized methionine is loss of 64 Da, which corresponds to loss of CH3SOH from
      the methionine sulfoxide. These fragments are useful in identifying peptides that
      include oxidized methionine residues.

PMID- 9257121
TI  - Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant
      defence enzymes in a healing cutaneous wound.
AB  - In the present investigation the involvement of free radicals in a self-healing
      cutaneous wound has been demonstrated. The levels of different enzymatic and non
      enzymatic antioxidants have been studied in 2,4,7 and 14 days old wounds and
      compared with normal skin. Except for glutathione reductase (GR), all other
      enzymatic and non-enzymatic antioxidants were found to decrease following
      wounding. The decrease was 60-70% in superoxide dismutase (SOD), glutathione
      peroxidase (GPx) and glutathione-S-transferase (GST) at 2, 4 and 7 days, while in
      the case of catalase (CAT) the decrease was 40-60% during this period. Although a
      complete recovery in the activity of CAT was observed, SOD and GPx did not
      recover completely and GST was found to be slightly elevated on 14th day post
      wounding. Non-enzymatic antioxidants viz, ascorbic acid, vitamin E and
      glutathione were also found to decrease to about 60-70% and except glutathione
      none of them was found to recover completely at 14th day postwounding.
      Interestingly thiobarbituric acid reactive substance (TBARS) expressed as
      malondialdehyde (MDA) equivalent, a marker of lipid peroxidation, decreased
      following wounding which could be because of meagre availability of lipid
      substrate and/or of ascorbic acid. The results indicate that wounding results in
      loss of different free radical scavengers both enzymatic and non-enzymatic which
      either partially or completely recover following healing.

PMID- 9257123
TI  - Measurement of menadione-mediated DNA damage in human lymphocytes using the comet
      assay.
AB  - The model quinone compound menadione has been used to study the effects of
      oxidative stress in mammalian cells, and to investigate the mechanism of action
      of the quinone nucleus which is present in many anti-cancer drugs. We have used
      the alkaline single cell gel electrophoresis assay (comet assay) to investigate
      the effects of low doses of this compound on isolated human lymphocytes. We found
      that concentrations of menadione as low as 1 microM were sufficient to induce
      strand breaks in these cells. Pre-incubation with the NAD(P)H quinone
      oxidoreductase inhibitor dicoumarol, enhanced the production of menadione-induced
      strand breaks. In contrast, the metal ion chelator 1,10-phenanthroline inhibited
      formation of strand breaks, although prolonged incubation with 1,10
      phenanthroline in combination with menadione resulted in an increase in a
      population of very severely damaged nuclei. A marked variation in the response of
      lymphocytes from different donors to menadione, and in different samples from the
      same donor was also observed.

PMID- 9257124
TI  - Novel connections between NADPH-induced lipid peroxidation and cytochrome P450
      inactivation, and antioxidant and enzyme protective properties of estradiol in
      gonadal membranes.
AB  - This study uses microsomal membranes from rat testis tissue, including the
      cytochrome P450c17 (steroid 17 alpha-monooxygenase/17 alpha-hydroxyprogesterone
      aldolase, catalyzing the conversion of progesterone to androstenedione), to
      decipher the possible relation of NADPH-induced (no exogenous iron added) lipid
      peroxidation and cytochrome P450 inactivation and the protective effect of
      certain steroids. NADPH (300 microM) causes a 3.6-fold stimulation of
      malondialdehyde formation (thiobarbituric acid-reactive substances) and a 29%
      cytochrome P450c17 loss within 1 h at 37 degrees C, but has no effect on lipid
      peroxidation in the presence of the iron chelator desferrioxamine. Hydrogen
      peroxide has only marginal effects. The antioxidant efficiency of estradiol (IC50
      = 13.9 microM) is higher than its cytochrome P450c17 protective efficiency (IC50
      = 33.0 microM), whereas androstenedione does not inhibit lipid peroxidation but
      protects cytochrome P450c17 completely. The human choriogonadotropin-induced
      degradation of cytochrome P450c17 in incubated decapsulated testes can not be
      correlated with a stimulation of lipid peroxidation, and it is partially
      inhibited by estradiol but completely abolished by androstenedione. It is
      concluded (I) that NADPH stimulates iron-dependent generation of reactive oxygen
      species by the monooxygenase system even in the presence of certain P450 ligands
      in the physiological membrane environment, (II) that membrane lipid peroxidation
      may be suppressed by hydrophobic steroids acting as antioxidants such as
      estradiol, (III) that steroid ligands stabilize cytochrome P450c17 against
      inactivation in the presence of NADPH even if they do not act as substrates and
      do not possess antioxidant activity, and (IV) that the choriogonadotropin-induced
      down-regulation of cytochrome P450c17 is not due to accumulating steroids acting
      as "pseudosubstrates" as occasionally supposed.

PMID- 9257125
TI  - Secondary bile acid induced DNA damage in HT29 cells: are free radicals involved?
AB  - Increased bile acid secretion, as a consequence of a high fat diet, results in
      the increased production of bile acids that may escape the enterohepatic
      circulation, and be subsequently metabolised by the colonic micro-flora to form
      the co-mutagenic and co-carcinogenic secondary bile acids. The potential of the
      secondary bile acids lithocholate (LOC) and deoxycholate (DOC), to induce DNA
      damage, in the colonocyte cell line HT29, at physiological concentrations both
      individually and in a 2:1 ratio was assessed. Results indicated significant
      levels of DNA damage induced by both bile acids, with LOC having the greater DNA
      damaging capacity. The potential role of vitamin A, and the antioxidant vitamin
      E, in reducing this damage was determined, over a range of vitamin
      concentrations. Both vitamins reduced the bile acid induced DNA damage. Vitamin A
      displayed a dose response relationship, whereas vitamin E reduced DNA damage
      close to negative control values at all concentrations above 50 microM. These
      results indicate a protective role for Vitamins A and E, against the DNA damaging
      capacity of LOC and DOC.

PMID- 9257126
TI  - High resolution 1H NMR investigations of the reactivities of alpha-keto acid
      anions with hydrogen peroxide.
AB  - The chemical reactivity of various alpha-keto acid anions (beta-hydroxypyruvate,
      beta-phenylpyruvate, 2-ketobutyrate and 2-ketoglutarate) with hydrogen peroxide
      (H2O2) was investigated at physiological pH (7.4) and a temperature of 25 degrees
      C. The initial concentration of the alpha-keto acid anions was kept constant at
      1.00 mM whilst that of added H2O2 was varied from 0.25 to 1.00 mM, and the rate
      and extent of these reactions was evaluated using 1H NMR spectroscopy. At all
      H2O2 concentrations utilised, the order of reactivity of the alpha-keto acid
      anions was beta-hydroxypyruvate > beta-phenylpyruvate > 2-ketobutyrate > 2
      ketoglutarate. The results obtained are in agreement with a proposed mechanism
      for these reactions, involving nucleophilic attack of the mono-deprotonated
      peroxide species (HO2-) at the C-2 carbonyl group carbon centre. The antioxidant
      capacity of such alpha-keto acids is discussed in terms of their potential use as
      therapeutic agents in clinical conditions where H2O2 has been shown to play a
      critical role in the disease process, i.e., those involving 'oxidative stress'.

PMID- 9257127
TI  - Synthesis and spin trapping applications of 2,2-dimethyl-d6-4-methyl-2H-imidazole
      1-oxide-1-15N.
AB  - A new spin trap, 2,2-dimethyl-d6-4-methyl-2H-imidazole-1-oxide-1-15N (lTMIO), was
      synthesized and characterized. Hyperfine splitting (HFS) constants of spin adduct
      ESR spectra of this compound with oxygen-centered, carbon-centered, thiyl and
      sulfite-derived radicals were determined and compared with the data of the
      unsubstituted compound. The increase in ESR spectral intensity and the
      accompanying decrease of the spectral linewidth result in resolution of the HFS
      due to interaction with alpha-protons of alkyl radicals trapped by lTMIO.
      Trapping of the formate radical in deoxygenated aqueous solution revealed a very
      low spectral linewidth (delta Bpp = 0.028 mT) of the corresponding adduct. A
      strong dependence of the ESR spectra on pH was observed when the autoxidation
      product of sulfite, SO3-, was trapped. The pKa was found to be 5.8 +/- 0.3. In
      comparison to other nitrones, application of this spin trap provides more
      detailed information on the structure of the species trapped, especially for
      carbon-centered radicals.

PMID- 9257128
TI  - Increase of lipid hydroperoxides in tissues of vitamin E-deficient rats.
AB  - The level of lipid hydroperoxides was determined by a newly developed method in
      rat tissues of vitamin E deficiency, which was a good in vivo model of enhanced
      radical reactions. In the heart, lung and kidney, the level of lipid
      hydroperoxides increased significantly as early as 4 weeks after feeding on a
      tocopherol-deficient diet compared with that of the control group. After 8 weeks
      of the deficiency, similar results were obtained. These results indicate that the
      lipid hydroperoxide is available as an extremely sensitive indicator of lipid
      peroxidation in these organs, because it takes several months to detect
      manifestations of the vitamin deficiency based on conventional indices.

PMID- 9257129
TI  - Plasma and LDL levels of major lipophilic antioxidants are similar in patients
      with advanced atherosclerosis and age-matched controls.
AB  - Oxidative modification of low-density lipoprotein (LDL), regarded an early event
      in atherogenesis, is associated with the depletion of the lipoprotein's
      antioxidants. We tested whether the levels of major lipophilic antioxidants in
      the blood of patients with advanced atherosclerosis are different to those in age
      matched controls. On average, plasma ubiquinol-10, total coenzyme Q and coenzyme
      Q redox status were slightly lower whereas the levels of alpha-tocopherol were
      slightly higher in patients (63 +/- 11 years, n = 32) than controls (64 +/- 10
      years, n = 24). However, these differences were not statistically significant (p
      > 0.05). The levels of antioxidants in LDL isolated from a subset of patients (n
      = 20) and controls (n = 15) were also indifferent, and hydroperoxides of
      cholesteryl esters were undetectable (detection limit 10 nM) in plasma of
      patients (n = 11) and controls (n = 10). The data suggests that plasma and LDL
      levels of lipophilic antioxidants are not depleted in patients suffering from
      severe atherosclerosis, and that neither parameter serves as a useful diagnostic
      indicator for this disease.

PMID- 9257130
TI  - Standardization of low attenuation area versus total lung area in chest X-ray CT
      as an indicator of chronic pulmonary emphysema.
AB  - We examined the methods for measuring the LAA% (100 x low attenuation area/total
      lung area) on thoracic X-ray CT scans in order to develop a useful indicator of
      chronic pulmonary emphysema (CPE). First, we modified the method for calculating
      the LAA% to be applicable by the programming tool installed in a commercially
      available CT machine in order to minimize manual procedures. This new method
      proved to be applicable in all CT machines produced after 1987. Second, we
      examined the difference in the Hounsfield Unit (HU) between different CT machines
      using two kinds of phantoms. One phantom was composed of Styrofoam, which has a
      density similar to the low attenuation areas. The other phantom was composed of
      Styrofoam and water, which has a density similar to the lung. We proved that the
      difference of LAA% with the correct value was 5% at maximum among four different
      CT machines. Thus, the phantom developed in the present study may play an
      important role in the standardization of HU. Finally, the possibility of
      decreasing the X-ray levels was examined. Twenty-five percent of the standard
      electrical current provided the same LAA% in cases where the subject was an
      established CPE patient, whereas the LAA% was overestimated in subjects with a
      normal LAA% value. However, a correction using a linear regression equation may
      be possible in the latter cases. It may be concluded that LAA% analysis can
      easily be performed in many city hospital, without much investment of manual
      procedures or any corrections to the HU levels between different CT machines.
      This method may be useful as a routine follow up for CPE patients because of the
      smaller irradiated dose given when using a CT machine.

PMID- 9257131
TI  - Complexity and frequency hierarchies in the catfish retina.
AB  - The intricate connectivity and interactions between neurons in the vertebrate
      retina have made their individual roles in signal processing very difficult to
      elucidate. We have used a recently developed mathematical tool, fast orthogonal
      search (FOS), to probe the catfish outer (distal) and inner (proximal) retina,
      and study the signal processing within. Through FOS, a given waveform can be
      decomposed into a parsimonious sinusoidal series containing the most significant
      constituent frequencies. In particular, we examined the light-evoked first-order
      Wiener kernels of horizontal cells and on-bipolar cells, and on-off, off- and on
      amacrine and ganglion cells. Here we report a hierarchy (correlation coefficient
      up to 0.86) in preferred frequency and complexity of response corresponding to
      the retina's structural hierarchy. In addition, clear differences between on-, on
      off and off-cell functional characteristics were detected. For example, the
      kernel waveform for the on-amacrine cell was found to be more complex and to have
      a higher preferred frequency than that for the off-amacrine cell. Indeed FOS
      analysis revealed that both off- (sustained) amacrine and off-ganglion cells
      exhibit significantly less complexity in their waveforms for signal processing of
      light input than do the corresponding on- and on-off cells. This shows a clear
      breakdown in symmetry between on- and off-pathways, and suggests that connections
      to off-cells may provide fewer or a smaller variety of inputs than those to on-
      and on-off cells. Many of our new findings can be appreciated by assuming an
      underlying cascade structure for the retinal information processing. The FOS
      findings in particular support the following previously advanced hypothesis: the
      transition in nonlinear processing from on-off amacrine to on- off-amacrine cells
      is due to high-pass linear filtering. Furthermore, our results indicate that the
      high-pass filtering is more sharply differentiating for the on-amacrine than for
      the off-amacrine cell.

PMID- 9257132
TI  - Developmental changes in functional EEG asymmetry: a multivariate autoregressive
      modeling approach.
AB  - To investigate the functional asymmetry of the electroencephalogram (EEG) in the
      developing brain, we analyzed quantitatively the different components of
      simulated EEG (SEEG) in a model before and after cutting off the intercerebral
      interaction. Original EEG (OEEG) recordings were obtained from 374 normal
      children aged 3-12 years. The SEEGs were computed from the OEEG after applying
      'ARdock', a new multivariate autoregressive (AR) modeling method. Subsequently,
      the univariate AR and component analysis was applied on OEEG and SEEG. The F
      value was computed from Mahalanobis' distance between both AR coefficients of
      component activities for age, EEG derivation and frequency band. Our analysis
      showed developmental lateralities in the alpha band at the frontal pole in 5 and
      12 year old children, and at the central region in 8 and 11 year old children.
      Our results suggest that the intercerebral interactions develop at approximately
      5 years of age at the left frontal pole during the period of maturation of alpha
      band activity and after 8 years of age when it replaced theta band activity. The
      present method of analysis may have a wide clinical application in the analysis
      of normal and abnormal EEGs.

PMID- 9257133
TI  - Controllability of temporomandibular joint loading by coordinative activities of
      masticatory muscles: a two-dimensional static analysis.
AB  - Masticatory and bite forces, when applied to the teeth, generate tremendous
      compressive energy in the temporomandibular joint (TMJ). Excessive 'TMJ loading',
      if left untreated, deteriorates articular functions. Normally, it is controlled,
      to a certain extent, by stomatognathic means. In an attempt to clarify this
      control mechanism, we analyzed the relationship between TMJ loading and the
      activities of the masticatory muscles, by employing a static two-dimensional jaw
      model. This comprises two rigid bodies, the upper and lower jaws, including three
      dominant muscles, i.e. the masseter, the anterior portion of the temporalis and
      the lateral pterygoid. Static equilibrium analyses determined that TMJ loading
      can be minimized, under controlled bite conditions, by pointing the loading
      vector in a direction solely indicated by individual morphological factors, such
      as the position and orientation of the masseter and the temporalis. This
      theoretically optimum direction of TMJ loading was also anatomically acceptable,
      because the load is applied exactly to those portions of the articular disk and
      mandibular head that can most easily sustain it. Interestingly, this factor was
      absolutely independent of both the activities of the lateral pterygoid and the
      direction of bite force. Consequently. TMI loading can be minimized, by
      coordinating the activities of the masseter and the anterior portion of the
      temporalis.

PMID- 9257134
TI  - High speed detection of R-R intervals for universal Holter recordings.
AB  - Heart rate variability (HRV) has been gaining popularity for its potential to
      estimate the autonomic nerve function and prognosis of patients with
      cardiovascular diseases. Holter recordings have been used for the measurement of
      R-R intervals in out-patients and for the estimation of circadian variations of
      HRV. However, when the manufacturer of the Holter tape recorder is not the same
      as that of the Holter analyzer a correction of the tape speed error for the
      accurate measurement of the R-R intervals is abandoned. The simultaneous
      assessment of additional physical parameters recorded on the Holter recorder and
      R-R interval is not possible with commercial software. To overcome these
      problems, we developed a system to detect R-R intervals at the playback speed of
      a Holter analyzer 500 times real-time with the correction of tape speed error
      from a system clock recorded on the Holter tape. High- and low-pass filter
      processed ECG signals and a comparator provided digital signals representing the
      R-R intervals. The R-R intervals and system clock intervals (tape speed) were
      measured simultaneously by interrupt-driven software, using timer-counters in a
      personal computer. The measured R-R intervals were corrected with the system
      clock intervals. The power spectra of the tape speed error showed that tape speed
      error significantly affects the power spectra of HRV, if not corrected. This
      method is applicable to Holter tape recorders of any manufacturer. This system
      also enables the simultaneous measurement of HRV and other physical parameters to
      evaluate their relations.

PMID- 9257135
TI  - Beyond sociodemographics: factors influencing the decision to seek treatment for
      symptoms of acute myocardial infarction.
AB  - OBJECTIVE: To determine the impact of sociodemographic, clinical, cognitive,
      emotional, and social factors on patient delay in seeking treatment for symptoms
      of acute myocardial infarction. DESIGN: Multicenter descriptive survey. SETTING:
      Forty-three hospitals in North America. SUBJECTS: Two hundred and seventy-seven
      patients with confirmed acute myocardial infarction enrolled in a thrombolytic
      clinical trial. OUTCOME MEASURES: Time from symptom onset to arrival at the
      hospital for treatment. RESULTS: Patients with longer delays were older, had
      lower incomes, had diabetes, experienced their symptoms at home, did not appraise
      their symptoms as serious or originating from the heart, had symptoms that were
      intermittent in nature, waited to see whether symptoms disappeared, worried about
      troubling others, feared what might happen if they sought treatment, and did not
      realize the importance of symptoms. CONCLUSION: Patient appraisal of seriousness
      of symptoms is related to delay, whereas severity, nature, and knowledge of
      symptoms are not related. Cognitive and emotional responses affect patients'
      decisions to seek treatment.

PMID- 9257136
TI  - Responding to symptoms and signs of acute myocardial infarction--how do you
      educate the public?: a social-psychologic approach to intervention.
AB  - In an era of highly time-dependent therapies for acute myocardial infarction
      namely thrombolytic therapy and cardiopulmonary resuscitation-it is imperative
      that public education programs facilitate expeditious care-seeking. However,
      community intervention studies to reduce the interval of time-from the onset of
      an acute myocardial infarction to arrival at a hospital emergency department-have
      shown ambiguous results. To understand and reduce this time interval, a theoretic
      model is proposed that draws from self-regulation theory. The combined model
      focuses on three issues: first, information for systematic sign-and-symptom
      recognition and labeling; second, behavioral information as to what to do in the
      event of an acute myocardial infarction; and third, information on how to control
      affective and emotional responses that may interfere with effective coping. Seven
      recommendations are made for guiding community intervention with use of the
      proposed model.

PMID- 9257137
TI  - Beliefs about medication and dietary compliance in people with heart failure: an
      instrument development study.
AB  - BACKGROUND: Sodium retention is often a precursor to hospitalization in people
      with heart failure (HF). Lack of compliance with medications and with dietary
      sodium restrictions affects sodium retention. OBJECTIVES: The purpose of this
      study was to evaluate the reliability and validity of the Beliefs about
      Medication Compliance Scale and the Beliefs about Dietary Compliance Scale.
      METHODS: The Beliefs about Medication Compliance Scale and the Beliefs about
      Dietary Compliance Scale are instruments we developed specifically to measure
      beliefs about compliance with behaviors that affect sodium retention in persons
      with HF. The scales, based on the Health Belief Model, were designed from a
      review of literature and from self-reports of people with HF. A convenience
      sample of 101 people with HF completed the scales. RESULTS: Internal consistency
      reliability was satisfactory. Factor analysis provided initial support for
      construct validity of the scales. CONCLUSIONS: Future testing of the scales is
      needed in more diverse populations. The scales can then be used to test
      interventions tailored to individual subjects' beliefs about compliance.

PMID- 9257138
TI  - The unique management of refractory advanced systolic heart failure.
AB  - Advanced systolic heart failure refractory to ambulatory pharmacotherapy
      continues to be a clinical dilemma with increasing incidence and prevalence. By
      establishing the presence of signs and symptoms, clinicians could better evaluate
      hemodynamic perturbations, therefore targeting them through the use of
      intravenous diuretics, intravenous vasodilators, and intravenous inotropic
      therapy. This review focuses on the unique features that characterize advanced
      heart failure, and discusses the special clinical considerations in managing this
      morbid entity.

PMID- 9257139
TI  - Rapid recovery management: the effects on the patient who has undergone heart
      surgery.
AB  - OBJECTIVE: To determine whether patients who have undergone heart surgery can be
      managed with use of rapid recovery guidelines without any subsequent increase in
      complication, mortality, or readmission rates. DESIGN: Retrospective study, two
      groups, comparative. SETTING: Private midwestern hospital with 690 licensed beds.
      SUBJECTS: Group I consisted of 312 adult patients who had undergone heart surgery
      in 1993 who were managed using traditional methods. Group II consisted of 303
      patients who had undergone heart surgery in 1994 who were managed using rapid
      recovery guidelines. OUTCOME MEASURES: Complications (pneumonia and wound
      infections), mortality, and readmission rates. RESULTS: Of the surgeries
      performed in 1994, 44% of the patients were discharged by postoperative day 4. No
      increase was noted in complication, mortality, and readmission rates.
      CONCLUSIONS: When compared to patients who were managed by traditional methods,
      these findings indicated that it is possible to manage adult patients who have
      undergone heart surgery using rapid recovery guidelines and maintain high-quality
      patient outcomes and level of satisfaction. In addition, cost savings and
      decreased resource use are added benefits.

PMID- 9257140
TI  - Endothelin-1: possible implications in pulmonary vascular disease.
AB  - The vasoactive properties of endothelin-1 (ET-1) in the animal model very with
      the tone of the pulmonary vessels, the dose level of ET-1, and the maturation of
      the vessels. The action of ET-1 is mediated by endothelium-derived nitric oxide,
      prostaglandins, and electrolytes. Plasma levels of ET-1 are elevated in pulmonary
      hypertension in both animals and humans. ET-1 antagonists may prove useful in
      treating pulmonary hypertension in children and adults.

PMID- 9257141
TI  - A guide to noninvasive intermittent ventilatory support.
AB  - Patients who use home-based medical technologies, such as noninvasive
      intermittent ventilatory support, may require hospitalization on units where the
      staff is unfamiliar with this type of equipment. Consequently, acute care
      clinicians need resources so they can provide safe care to these patients. This
      article provides background information about noninvasive intermittent
      ventilatory support, presents a case study to illustrate key aspects of each type
      of support, and provides quick reference tables to assist acute care clinicians
      in managing this technology.

PMID- 9257142
TI  - Opioid and benzodiazepine tolerance and dependence: application of theory to
      critical care practice.
AB  - Critical care clinicians frequently manage patient pain and agitation and promote
      ventilator stability through use of opioids and benzodiazepines. Often, doses of
      these drugs must be increased considerably over time as they lose their
      effectiveness-an indication of drug tolerance. Furthermore, patients can
      experience negative physiologic responses to withdrawal of these drugs-an
      indication of drug dependence. Withdrawal symptoms due to abrupt discontinuation
      of drug therapy can be profound and dangerous. It is important that clinicians
      understand the mechanisms of drug therapies and their potential negative
      sequelae. The purpose of this article is to present physiologic theories of
      opioid and benzodiazepine actions, as well as drug tolerance and dependence, as a
      basis of knowledge for clinical practice. A clinical scenario of an intensive
      care unit patient is presented, and a care plan is offered, to provide guidance
      to practitioners who care for patients experiencing the consequences of long-term
      opioid and benzodiazepine use.

PMID- 9257144
TI  - Reducing resource consumption through work redesign in a surgical intensive care
      unit: a multidisciplinary, protocol-based Progressive Care Area.
AB  - Patients with prolonged intensive care unit (ICU) length of stay, though few in
      number, consume as much as 50% of ICU resources. With increasing pressures for
      cost containment in health care, the availability of ICU beds may be jeopardized.
      To improve the efficiency of care for patients requiring a surgical intensive
      care unit (SICU) stay of 3 or more days, a multidisciplinary, highly
      "protocolized," Progressive Care Area was developed within the existing SICU
      environment. Entry into this area is limited to patients whose acuity level is
      not high by ICU standards, but too high for a general surgical floor. In
      designing the Progressive Care Area, we drew on a number of published management
      strategies-including total quality management concepts and our prior experience
      in establishing ventilator management teams. The Progressive Care Area has
      resulted in a reduction in both the frequency and variation of resources used. A
      Progressive Care Area within an existing ICU is a viable alternative for the care
      of the patients who have prolonged lengths of stay and are less acutely ill, and
      it significantly improves ICU efficiency.

PMID- 9257143
TI  - Cardiac monitoring after phenytoin overdose.
AB  - OBJECTIVE: To evaluate whether patients admitted to the hospital with oral
      phenytoin overdose should receive cardiac telemetry monitoring. DESIGN:
      Retrospective chart review over a 4-year period. SETTING: Eastern United States
      community teaching hospital. PATIENTS: Forty-four patients admitted with a
      diagnosis of oral phenytoin overdose, with a toxic serum concentration defined as
      a peak level higher than 20 micrograms/ml, who had electrocardiography performed
      both at the time of admission and after the phenytoin level had decreased below
      the toxic threshold. INTERVENTIONS: None. RESULTS: Chi-square, t test, and
      Fisher's exact tests were used for analysis. Mean peak phenytoin concentration
      was 36.7 +/- 12.1 micrograms/ml, with a maximum concentration of 75
      micrograms/ml. Electrocardiograms recorded at the time of hospital admission in
      all 44 cases revealed no clinically significant abnormalities attributable to
      phenytoin when toxic and posttoxic states were compared. There were no
      circulatory complications or deaths. CONCLUSION: Patients admitted with oral
      phenytoin overdose with serum concentrations as high as 75 micrograms/ml did not
      experience any significant cardiovascular arrhythmias or complications. Patients
      with oral phenytoin overdose do not warrant routine admission to a telemetry bed
      for management of their condition.

PMID- 9257146
TI  - Risk factors for the development of colorectal carcinoma and their modification.
AB  - In this article the authors review factors determining risk for the development
      of colorectal cancer (CC) and their modification. Emphasis is placed on
      understanding the difference between average risk and high risk individuals. Risk
      factors including genetics, diet, environment, and coexistent diseases are
      discussed. The data regarding modification of risk via dietary, pharmaceutical,
      and prophylactic endoscopic and surgical interventions are reviewed.

PMID- 9257147
TI  - Screening and surveillance for colorectal carcinoma.
AB  - Screening and surveillance examinations are effective in lowering colorectal
      cancer risk. Screening tests have been demonstrated to reduce colorectal cancer
      mortality. Colonoscopic removal of adenomatous polyps has been determined to
      reduce colorectal cancer incidence. High-risk individuals and their family
      members should be identified and offered more aggressive recommendations for
      appropriate screening and surveillance guidelines. Colorectal cancer screening
      strategies are in an acceptable range of cost effectiveness.

PMID- 9257145
TI  - Intravenous line infection due to Ochrobactrum anthropi (CDC Group Vd) in a
      normal host.
AB  - Ochrobactrum anthropi, formerly known as Achromobacter species (CDC group Vd), is
      an aerobic, gram-negative bacillus widely distributed in aquatic environments.
      Most important, it has been implicated as a cause of intravenous line infection
      in immunocompromised hosts with solid tumors or hematologic malignancies.
      Trimethoprim-sulfamethoxazole and aminoglycosides are usually active against O.
      anthropi, but this organism is usually resistant to beta-lactam antibiotics.
      Because O. anthropi is a low-virulence organism, patients with intravenous-line
      infections have been cured without removal of the intravenous catheter. We
      describe a case of intravenous-line infection in a normal host that was
      successfully resolved alter catheter removal.

PMID- 9257149
TI  - Preoperative and postoperative imaging for colorectal cancer.
AB  - Management and survival in colorectal cancer are dictated by the extent of the
      disease at the initial diagnosis. Technological advances over the past 25 years
      have improved the ability to accurately preoperatively stage these lesions and
      detect recurrence. This article reviews the focus on the utility of computerized
      tomography, magnetic resonance, endoscopic ultrasound, and newer imaging methods
      including PET scan and monoclonal antibodies in the management of colorectal
      carcinoma.

PMID- 9257148
TI  - Molecular pathogenesis of colorectal cancer.
AB  - The enormous progress made in the identification of genes that are involved in
      colon carcinogenesis has provided the foundation for further understanding the
      biology of both normal and cancer cells and for targeted therapeutic strategies.
      In one sense, the genes described in this review are only the building blocks of
      a larger puzzle that constitutes the integrated metabolic function of a cell. The
      current challenge is to understand the functional role of these genes in normal
      cellular physiology and make the connections between pathways that knit together
      integrated cellular homeostasis. A complete understanding of the regulatory
      pathways, and the synthesis and modifications of the proteins involved, will
      provide novel targets for therapeutic agents.

PMID- 9257150
TI  - Surgical aspects of colorectal carcinoma.
AB  - Colorectal surgery remains the cornerstone of curative therapy for colorectal
      carcinoma. The development of new instruments permitting technical advances,
      however, as well as the advent of effective adjuvant therapies and the progress
      in staging and early detection, have changed some of the indications for surgery
      as well as surgical methods. Even so, emphasis has always been placed on thorough
      preoperative evaluation and staging. This article explores the current state of
      standard surgical care of the colorectal cancer patient with special attention
      given to preoperative evaluation, standard and controversial surgical therapies,
      and postoperative surveillance.

PMID- 9257151
TI  - The role of adjuvant radiation therapy in the treatment of colorectal cancer.
AB  - Radiation therapy in conjunction with 5-FU chemotherapy is an effective method in
      the adjuvant treatment of both colon and rectal cancer.

PMID- 9257152
TI  - The role of adjuvant chemotherapy in the treatment of colorectal cancer.
AB  - Adjuvant therapy is clearly of great benefit for certain patients with colorectal
      carcinoma. Validation of new prognostic markers to further define which patients
      are at highest risk of recurrence will be important. Future investigation for
      adjuvant therapy includes incorporation of achievements made in the advanced
      disease setting, including biochemical modulation of 5-FU, identification of new
      active agents, and incorporation of immunotherapy strategies into adjuvant
      treatment programs. Further improvements in the treatment of these patients, even
      if small, may translate into important benefits, given the large number of
      patients presenting annually with this common cancer. As our therapeutic options
      broaden and improve, investigators will need to focus on quality of life and
      pharmacoeconomic parameters to determine which adjuvant approaches are optimal
      for the individual patient with colorectal cancer, as well as for society in
      general.

PMID- 9257153
TI  - Experimental chemotherapeutic agents for the treatment of colorectal carcinoma.
AB  - Colorectal cancer is the third leading cause of cancer mortality for men and
      women in the United States. For the past 40 years fluorouracil has been the only
      agent with significant activity in this disease. More recently, advances in our
      understanding of the molecular biology of cancer have permitted the development
      of effective new agents for this disease. This article examines the current and
      future status of these new agents.

PMID- 9257154
TI  - The approach to the patient with single and multiple liver metastases, pulmonary
      metastases, and intra-abdominal metastases from colorectal carcinoma.
AB  - Recurrent colorectal carcinoma constitutes a major health care problem, with
      90,000 patients diagnosed annually with metastatic disease. Recent advances have
      offered treatment to selected patients with liver, lung, and intra-abdominal
      metastases. Resection of liver secondary tumors improves 5-year survival from 0%
      to approximately 30% and offers the only possibility for cure. As experience
      mounts, hepatic surgery can be performed with quite acceptable morbidity and
      mortality. Adjuvant therapies are being developed that may improve results with
      surgery alone. Cryoablation is a new technique that appears to effectively
      eradicate liver tumors, but its role remains to be defined. In patients with
      unresectable disease, the benefit of hepatic artery infusion of chemotherapy is
      unproven. Resection of pulmonary metastases significantly improves survival in
      patients with solitary nodules. Consistent data regarding the benefit of
      pulmonary metastatectomy in patients with multiple nodules are not available.
      Combined cytoreductive surgery and intraperitoneal hyperthermic chemotherapy is
      being investigated as a treatment for peritoneal carcinomatosis from colorectal
      cancer. Although selected patients may benefit, this combined treatment modality
      appears to be less effective in patients with colorectal cancer than with other
      types of cancer.

PMID- 9257155
TI  - Chemoprevention for colorectal carcinoma.
AB  - The literature on chemoprevention for colorectal carcinoma can be summarized as
      follows: (1) Aspirin and NSAIDs usage can decrease polyp formation and promote
      polyp regression and have a strong epidemiologic link to colorectal cancer
      prevention. (2) Fiber intake is strongly associated with a decreased incidence of
      colorectal carcinoma. Whether supplemental fiber can prevent colorectal neoplasia
      is not yet clear. (3) Calcium and vitamin D intake is inversely proportional to
      the risk of developing colorectal carcinoma. Prospective trials make the role of
      supplemental calcium as a chemoprotective agent unclear: (4) Chemoprevention is
      an exciting area of research. More work needs to be done to establish the precise
      steps necessary for neoplastic transformation of cells so that pharmaceuticals
      can be developed to target carcinogenesis at several levels.

PMID- 9257156
TI  - Future directions for the treatment of colorectal carcinoma.
AB  - Most of these therapies, although still in the infant stages of their
      development, offer the potential for major advances in colorectal cancer therapy.
      Gene therapy is an entirely new medicinal paradigm for the treatment of cancer.
      Currently, the clinical application of these methods is limited by the need for a
      more through understanding of cancer immunology and the availability of better
      vector systems for efficient and selective tumor gene transfer. As increasing
      numbers of scientists and clinicians address these issues, better therapies will
      likely emerge.

PMID- 9257157
TI  - Pharmacological protection of NSAID-induced intestinal permeability in the rat:
      effect of tempo and metronidazole as potential free radical scavengers.
AB  - Recently, NSAID-induced changes in both the structure and function of the distal
      intestine have been found to occur more frequently and with greater toxicological
      significance than previously thought. We have previously validated a suitable
      animal model to evaluate intestinal permeability changes using orally
      administered 51Cr-EDTA that correlates with intestinal ulceration. In this study
      we investigated the suitability of metronidazole and the nitroxide stable free
      radical scavenger (tempo) as protective agents against NSAID-induced intestinal
      permeability. Male Sprague-Dawley rats were dosed with two doses of metronidazole
      (50 mg/kg, 12 and 1 h pre-NSAID) or a single 100 mg/kg dose of tempo 1 h prior to
      NSAIDs. The urinary excretion of the orally administered marker 51Cr-EDTA was
      measured. Both tempo and metronidazole dramatically reduced indomethacin (20
      mg/kg) and flurbiprofen (10 mg/kg)-induced intestinal permeability. All the
      animals exposed to indomethacin alone died within 48-96 h and presented with
      histological evidence of drug-induced enteropathy, ulceration and frank
      peritonitis. Protection by tempo and metronidazole suggests that free radicals
      and/or bacteria may be important mediators in the pathogenesis of intestinal
      mucosal damage induced by NSAIDs. Nitric oxide donor compounds used concomitantly
      with NSAIDs may protect gastrointestinal tract.

PMID- 9257159
TI  - Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and
      lung cancer.
AB  - 1. Genetic variation at the glutathione S-transferase M1 locus (GSTM1) has been
      associated with a number of apparently unrelated cancers, including lung cancer.
      Emphysema is a common lung disease often found concomitant with lung cancer. Both
      emphysema and lung cancer may result from chemical and oxidative damage caused by
      reactive species present in cigarette smoke or released from neutrophils
      recruited following cigarette smoke induced injury. GSTM1 may protect against
      such damage through detoxification of cigarette smoke components. Polymorphism of
      this gene may thus influence susceptibility not just to lung cancer, but to other
      forms of lung disease. 2. Resection specimens from a group of 168 lung cancer
      patients were assessed for the presence of macroscopic centriacinar and panacinar
      emphysema. DNA was extracted from archival material and genotyped for the GSTM1
      polymorphism using the polymerase chain reaction. A control group of 384
      anonymous blood donations was used to determine the frequency of the GSTM1 gene
      deletion in a random control population. Reverse transcription on lung tissue was
      performed to investigate mRNA expression of GSTM1 and GSTM4. 3. In 57 lung cancer
      cases with no emphysema there was no association with homozygous deletion of the
      GSTM1 gene (51% null in cancer and 53% null in control groups). However in 111
      patients with emphysema and lung cancer there was an increase in the frequency of
      deletion (65%, P = 0.032) giving an odds ratio of 1.36(0.32-2.40). In 43 cases
      there was evidence of both centriacinar and panacinar emphysema. The frequency of
      GSTM1 deletion was 70% (Odds ratio 2.11, 0.97-3.25). Both GSTM1 and GSTM4 mRNAs
      were expressed in lung tissue. 4 These findings suggest that GSTM1 has a general
      but rather small protective effect against toxicological injury in the lung which
      is not specific to cancer. This is of relevance in considering the health effects
      of exposure to a wide range of reactive chemicals in the environment.

PMID- 9257158
TI  - Media composition modulates excitatory amino acid-induced death of rat cerebellar
      granule cells.
AB  - This study examined the effects of maintaining cells in different media and the
      role of serum in glutamate and NMDA-induced neurotoxicity in rat cerebellar
      granule cells. Glutamate stimulated a concentration-dependent cell death with
      similar potency in cerebellar granule cells grown in BME and Neurobasal media
      without serum. However, the maximal cell death to glutamate and N-methyl-D
      aspartate (NMDA) varied in the different media compositions. In the presence of
      serum, glutamate and NMDA-induced excitotoxicity was abolished, suggesting a
      factor(s) in serum which influences glutamate-receptor mediated death. The
      protective effect of serum could be overcome by chronic stimulation with high
      doses of glutamate. The glutamate-stimulated increase in intracellular calcium
      load was attenuated in the presence of serum, resulting from an elevated basal
      calcium level, suggesting an association between raised basal calcium and
      neuroprotection.

PMID- 9257160
TI  - Writing case histories.

PMID- 9257161
TI  - Misunderstanding and psychic truths.
AB  - The author begins by pointing out that the psychoanalytical method and the
      concept of the unconscious are necessary conditions if the concept of psychic
      reality is to maintain its psychoanalytical relevance. She emphasises the
      importance of the concept of Nachtraglichkeit, or retroactive assignment of new
      meaning, as a link between the concepts of psychic reality and historical truths
      on the one hand and decentred listening and misunderstanding on the other.
      Recalling the Freudian development of the concept of psychic reality, she
      stresses that 'the other' is present from the outset in the constitution of the
      psyche; she discusses the relations between intrasubjectivity and
      intersubjectivity in the transference and concludes that, through the function of
      'listening to listening', misunderstanding becomes the royal path to the
      discovery of the patient's psychic reality. Some clinical examples are discussed
      in detail to illustrate the function of decentred listening. The author's
      viewpoint is not based on criteria concerning a correspondence, or lack of
      correspondence, between psychic reality and material reality. Her aim is to link
      psychic reality and historical truths as a way of overcoming solipsism.

PMID- 9257162
TI  - Distortions of time in the transference: some clinical and theoretical
      implications.
AB  - The author considers that patients' distortions of time can frequently and
      readily be observed in clinical psychoanalysis, reflecting both their
      psychopathology and their reactions to the temporal aspects of the psychoanalytic
      setting. These phenomena are considered in order to examine the assumptions that
      can implicitly be made about the nature of space and time in object-relations
      theory. Two case histories are given to exemplify these clinical phenomena-the
      first being an example of a fixation and the second one of a psychic retreat.
      These cases are compared to demonstrate the unconscious processes underlying the
      particular time distortions being considered, their impact on the patient's lives
      and their manifestation in the clinical setting. On the basis of these studies,
      it is suggested that the asymmetry of the 'arrow of time' cannot be assumed in
      the structure of psychic reality. The clinical evidence suggests that psychic
      reality has to be seen as discontinuous and that the structure of the
      discontinuities is revealed by the impact that the temporal aspects of the
      psychoanalytic setting have on the patient.

PMID- 9257163
TI  - The role of working through in bringing about psychoanalytic change.
AB  - In reviewing psychoanalytic case summaries while serving on the Committee on
      Certification of the American Psychoanalytic Association, the author gradually
      became aware that there was a recognisable similarity in what the analysands
      experienced in spite of variations among psychoanalysts as to how they conducted
      the analyses. Based on this observation, the author turned to his own clinical
      practice where more detailed process data was available, and focused his
      attention in particular on what the analysand does during a psychoanalysis. A
      detailed explication is offered of his findings, with a focus on the nature of
      'working through'. A clinical vignette is given to highlight that what the
      analysand experiences is an essential ingredient in attempting to understand how
      structural change occurs in psychoanalysis.

PMID- 9257164
TI  - Winnicott and the capacity to believe.
AB  - Like Freud's, Winnicott's writing displays an enormous interest in words, in
      their histories as well as their current usage. The author discusses his use of
      two words, 'capacity' and 'belief' combined in the phrase 'capacity to believe'.
      What Winnicott has to say about this capacity sheds light on the nature of both
      religious and cultural experience generally. The paper's argument has two strands
      that are woven together throughout. The first is Winnicott's concern for words
      and how a knowledge of their roots can enrich their current meaning. The second
      is his concern for the nature of belief, the 'capacity to believe', and his
      conviction that in exploring this capacity psychoanalysis might have something to
      teach religion. These concerns are interrelated in a number of ways in
      Winnicott's writing and are ultimately connected with his notion of a 'cultural
      field', a place to grow, where 'inventiveness', even verbal inventiveness, is
      'just one more example ... of the interplay between separateness and union', that
      is the separateness of individual language users but also their union through the
      language they share.

PMID- 9257165
TI  - Child and adolescent psychoanalysis: research, practice and theory.
AB  - In the last fifteen years, there have been three major developments in child and
      adolescent psychoanalysis and psychoanalytically informed psychotherapy. After
      briefly reviewing what is clear and unclear about the nature of child
      psychoanalysis, the author describes and critiques three recent trends: (1) a
      greater differentiation of aetiological factors that involves an enhanced
      understanding about developmental influences and how they may be utilised
      therapeutically; (2) a shift in child analytic theory to a more equitable balance
      between internal and external factors, with more attention being paid to the
      external; and (3) a significant increase in the psychoanalytically informed,
      empirical study of development as well as the process and outcome of treatment.
      Changes in these three overlapping domains are examined and their relevance to
      clinical practice discussed. It is suggested that the increase in the systematic
      and empirical study of the child psychoanalytic process has been the most
      significant recent development in the field; it is this that has the greatest
      potential to minimise rhetoric, to support discovery and to clarify what is
      unique about psychoanalytically informed work with children and adolescents.

PMID- 9257166
TI  - Towards a clinically and empirically sound theory of motivation.
AB  - The author outlines a theory of motivation that attempts to integrate
      psychoanalytic theory with current psychological thinking and research. Emotions
      and other sensory feeling states are evolved mechanisms for channelling behaviour
      in directions that foster adaptation. The avoidance of unpleasant states and
      pursuit of pleasant ones leads to goal-directed mental and behavioural processes,
      including defences and compromise formations. Affects provide a flexible
      motivational mechanism in humans, as they become associated with representations
      of perceived, feared, wished-for, or otherwise valued states through the
      interaction of environmental events and highly specific naturally-selected
      biological proclivities. This reconceptualisation of motivation points towards a
      resolution of a contradiction in Freud's models of affect and motivation between
      a theory of drive-reduction and a theory of affect regulation, and of the
      apparent contradiction between motivational models that emphasise either sexual
      desire or relational needs. The model also has implications for the theory of
      transference, since it suggests that neutrality is not the feature of the
      analytic situation that evokes meaningful transferential processes.

PMID- 9257167
TI  - The manic defence in analysis: the creation of a false narrative.
AB  - The author presents clinical material from the analysis of a patient who made
      sense of his chaotic life by creating seamless narratives in the analytic
      situation. Initially, his experience of meaning was derived from the form of his
      narrative. He repeatedly constructed the 'perfect' narrative, which he related to
      as a real object and as an object of reparation. There was a significant change
      in his narrative style and his experience of meaningfulness when he was able to
      struggle with the contradictions, ambiguities and inconsistencies in his life.
      The author argues that the patient's earlier narrative style, which he calls the
      manic narrative, is an aspect of the manic defence, whereas his later approach,
      when he relinquished the manic narrative in favour of a genuine experience of
      meaningfulness, was a move towards accepting depressive anxiety and acknowledging
      the state of his objects.

PMID- 9257168
TI  - Intimidation at the helm: superego and hallucinations in the analytic treatment
      of a psychosis.
AB  - On the basis of the development in the course of analytic treatment of a young
      male patient in a state of hallucinatory terror, the author discusses in this
      paper the nature of the psychotic superego. He shows how the process of
      recomposition of the self after a psychotic breakdown involves the transition
      from a terrorising and destructuring type of superego to one more reminiscent of
      that seen in depressive illness. The author describes this process against the
      background of the variations in the auditory hallucinations that began during the
      analysis. In the first phase of the analysis the patient is helped to free
      himself from the intimidating power of the hallucinatory superego, while the
      second phase centres on the patient's own involvement in producing the
      hallucinations. The author shows how the analysis mitigated the destructive hate
      resulting from unbearable psychic pain and describes how insight and
      transformation gradually ensued in the hallucinatory state. The resulting
      restoration of an internal psychic space is stated to be essential to the
      reconstitution of a whole and separate self. After drawing an interesting
      parallel between the psychotic superego and the attitude of God in the Old
      Testament story of Job, the author places his thesis in the context of the ideas
      of Klein, Bion and Rosenfeld.

PMID- 9257169
TI  - The umbilicus as sexual focus.

PMID- 9257170
TI  - Personal recollections and impressions of Harry Guntrip.

PMID- 9257171
TI  - The aim of psychoanalysis in theory and in practice.

PMID- 9257173
TI  - How brain development is shaped by genetic and environmental factors.

PMID- 9257175
TI  - The computer-based patient record as a CQI tool in a family medicine center.
AB  - BACKGROUND: In 1994 the Department of Family Medicine (DFM) at the Medical
      University of South Carolina (MUSC) developed an innovative infrastructure for
      continuous quality improvement (CQI) which capitalized on its existing computer
      based patient record (CPR) system. CQI PROGRAM: The CPR is a key element in all
      components of the DFM patient care CQI activities. Computerized record reviews,
      online queries, and special reports provide the background information needed to
      establish CQI projects and, in some cases, diagnose the cause. Any data entered
      into the CPR, including progress notes text, is searchable for use by the quality
      improvement teams. The most compelling aspect of DFM's CPR-based CQI system is
      the use of quality control charts that are regularly generated by the research
      division from CPR data. These charts allow the CQI teams to determine whether any
      changes in the process measurements are due to chance causes or are caused by
      specific interventions introduced to improve the process. ONGOING IMPROVEMENT
      PROJECTS: Four ongoing improvement projects that rely on CPR data and use
      electronically created control charts are discussed--optimizing the treatment of
      acute bronchitis, improving adherence to practice guidelines for patients with
      adult onset diabetes mellitus, improving the recognition and treatment of tobacco
      abuse, and improving blood pressure control in patients with hypertension. Each
      improvement project has a unique set of goals and objectives, against which the
      project's success is measured. CONCLUSION: A CPR system can be used to provide
      fast, organized access to large amounts of patient information to support
      structured quality improvement activities.

PMID- 9257176
TI  - Laboratory process improvement through point-of-care testing.
AB  - BACKGROUND: In the 1992-1996 period Methodist Clinical Laboratory Services of the
      Methodist Health Group, Indianapolis, was restructuring all work processes. In
      one initiative, point-of-care testing (POCT) was used to optimize the decision
      cycle time while reducing the overall cost of providing information. DEVELOPING
      THE COMPARATIVE MODEL: In a typical month (May 1994) for hospital admissions and
      laboratory usage, events related to the traditional blood analysis process were
      observed. In March 1995 the same model that was applied to analyze the
      traditional blood analysis process was used to evaluate the newly implemented
      POCT blood analysis process. Comparisons of both processes, cost per test panel,
      nursing time spent, and overall turnaround time were made between the two
      methodologies. RESULTS: A restructure of delivery of blood analysis with the POCT
      system saved the hospital $392, 336 compared to the total annual cost of the
      traditional approach for delivering blood analysis. The average cost per test
      panel was $15.33 with the traditional model and $8.03 with the POCT system.
      Improvements in the overall turnaround time of test results affected the decision
      cycle time of the caregiver. The POCT system saved four steps on the patient care
      floor and ten in the laboratory. DISCUSSION: It is critical to establish a POCT
      committee, including the most vocal critics of POCT1-to look at how a program of
      this nature will affect the organization. CONCLUSIONS: POCT became more than just
      an isolated change-it became a core strategy of moving laboratory testing out of
      the traditional laboratory setting to where it could become immediately
      accessible to caregivers as information.

PMID- 9257178
TI  - Increasing clinical prevention efforts in a family practice residency program
      through CQI methods.
AB  - BACKGROUND: As primary care physicians develop ongoing relationships with their
      patients, each contact provides another opportunity for primary, secondary, or
      tertiary prevention activities. In 1991 an interdisciplinary prevention project
      team using continuous quality improvement (CQI) principles was established to
      improve family practice residents' provision of such services. DIAGNOSTIC
      JOURNEY: For a random sample of 60 patient charts, abstractors looked for
      documentation of 23 clinical preventive services, including nursing screens,
      physician on-site and off-site implemented services, lifestyle education (diet,
      tobacco use), and self-screening education. After the chart review, the
      physicians, nurses, residents, and clinical staff used a fishbone analysis to
      identify physician-, clinic system-, and patient-centered factors contributing to
      the lack of conformance with clinical prevention guidelines. REMADIAL JOURNEY:
      The residency program began a series of didactic sessions on clinical prevention
      and instituted a procedures rotation to teach prevention procedure skills such as
      flexible sigmoidoscopy, stress testing, and colposcopy. On the CQI team's
      recommendation, a checklist developed by physicians and staff which itemized age-
      and gender-specific clinical prevention services was placed at the front of all
      patient charts. Clinic-system and patient factors were also addressed. HOLDING
      THE GAINS--MONITORING PERFORMANCE: The 1993 postintervention chart review showed
      significant improvements for 17 (81%) of the 21 targeted services. DISCUSSION:
      Providing educational sessions on prevention, permitting residents to select the
      areas of prevention on which to focus, and giving feedback on resident and staff
      performance through ongoing, nonpunitive monitoring resulted in increased
      provision of clinical prevention services in a family practice residency training
      center.

PMID- 9257177
TI  - Developing indicators for the Medicare Quality Indicator System (MQIS):
      challenges and lessons learned.
AB  - BACKGROUND: The Medicare Quality Indicator System (MQIS), initiated in 1993, was
      intended to form the basis for the Health Care Financing Administration's
      (HCFA's; Washington, DC) hospital-based quality measurement system. The MEDSTAT
      Group (Washington, DC) established quality indicator development methods for five
      clinical conditions, including early-stage breast cancer, diabetes mellitus, and
      upper gastrointestinal and lower intestinal bleeding. DEVELOPMENT OF QUALITY
      INDICATORS: Five national expert panels were convened to identify scientifically
      based hospital processes of care related to positive patient outcomes, as
      described in research studies and/or broadly accepted by the medical and allied
      health professions as indicators of high-quality care. LESSONS AND CHALLENGES:
      One of the most important lessons learned was the need for a narrow clinical
      focus for each quality indicator module. If the focus was adequately narrowed,
      all other tasks could be accomplished more efficiently and less ambiguously.
      Also, selection of the expert panel chair should occur early because of the
      chair's pivotal contributions to the clinical focus selection, literature review,
      and development of draft quality indicators. Perhaps the most starting finding
      and biggest challenge was the paucity of scientifically sound literature to
      support the clinical topics; except for the breast cancer studies, most of the
      available literature was categorized as flawed to some degree. A critical
      challenge for development of quality indicators is to translate what has been
      learned from the best scientific efficacy studies into indicators of effective
      rather than efficacious care. CONCLUSIONS: In choosing quality indicators,
      disease incidence and potential for quality improvement are important parameters.
      Although the former is relatively easy to define, the latter is not.

PMID- 9257179
TI  - X-ray photoelectron spectroscopy (XPS) surface analysis of HEMA-MMA
      microcapsules.
AB  - High resolution carbon, C 1s, X-ray photoelectron spectroscopy (XPS) of the
      surface of hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA; 75 mol% HEMA)
      capsules maintained in PBS for 1 week showed that the surface was not pure HEMA
      MMA. In these spectra, more carbon was bonded in the C-O form than in the C-C
      form indicating the presence of the Pluronic surfactant, L101, adsorbed from the
      precipitation bath to the surface during microcapsule preparation. Capsules
      maintained in medium containing fetal bovine serum for 1 week showed a nitrogen
      signal consistent with the presence of adsorbed serum proteins. There was a
      decrease in the amount of nitrogen on the surface after phosphate buffered saline
      (PBS) washing, however this did not decrease to zero. These preadsorbed proteins,
      present on the surface of capsules incubated in serum-containing medium before
      their implantation, may affect the tissue response to these capsules. Calcium was
      not detected on freshly-made capsules or capsules maintained in PBS for 1 week
      but was detected on capsules maintained in medium containing serum. Calcium
      deposits, if formed in vitro, could act as nucleation sites for calcification of
      the polymer in vivo.

PMID- 9257181
TI  - Comparative behavior of E. coli and S. aureus regarding attachment to and removal
      from a polymeric surface.
AB  - Staphylococcus aureus was found to attach more readily on polypropylene fibers
      with greater resistance to subsequent washing off than Escherichia coli after
      immersion of the fibers up to 300 s in pure culture suspensions in mineral salts
      medium. Each of five different washing solutions were effective against E. coli,
      whereas only a solution that contained SDS was effective against S. aureus.
      Placement of inoculated fibers on nutrient agar for longer periods of time
      resulted in greater resistance to washing by both organisms, although S. aureus
      remained more resistant than E. coli.

PMID- 9257180
TI  - Surface studies of albumin immobilized onto PE and PVC films.
AB  - The aim of this study is to evaluate the thrombogenic behaviour of the low
      density polyethylene and poly(vinyl chloride) modified by radiation-grafting
      technique. After copolymerization with acrylic acid by gamma-rays from a 60Co
      source, BSA was immobilized onto functionalized graft copolymers. The biological
      interaction between these materials and blood was studies by in vitro methods.
      The BSA immobilization effectively suppressed the adhesion and activation of
      platelets when it contacted whole blood.

PMID- 9257182
TI  - Double-stimuli-responsive degradation of hydrogels consisting of oligopeptide
      terminated poly(ethylene glycol) and dextran with an interpenetrating polymer
      network.
AB  - Biodegradable hydrogels consisting of oligopeptide-terminated poly(ethylene
      glycol) (PEG) and dextran (Dex) with an interpenetrating polymer network (IPN)
      structure were prepared as models of novel biomaterials exhibiting a double
      stimuli-response function. The IPN-structured hydrogels were synthesized by
      sequential cross-linking reaction of N-methacryloyl-glycylglycylglycyl-terminated
      PEG and Dex. In vitro degradation of the IPN-structured hydrogels was examined
      using papain and dextranase as model enzymes of hydrolyzing oligopeptide and Dex,
      respectively. Specific degradation in the presence of papain and dextranase was
      observed in the IPN-structured hydrogel with a particular composition of
      oligopeptide-PEG and Dex. This same hydrogel was not degraded by one of the two
      enzymes. The IPN-structured hydrogels were characterized by water content,
      thermal mechanical analysis, and wide-angle X-ray diffraction, and the results
      were compared with those of co-cross-linked hydrogels consisting of N
      methacryloyl-glycylglycylglycyl-terminated PEG and methacryloyl Dex. The results
      suggest that the IPN-structured hydrogels contain physical chain entanglements
      between networks as well as chemical cross-linked networks. It is concluded that
      the double-stimuli-responsive degradation observed in the IPN-structured hydrogel
      is achieved by controlling the chain entanglements between the two biodegradable
      polymers. Such degradation property of the IPN-structured hydrogel can be useful
      as a fail-safe system for guaranteed drug delivery and/or medical micromachines.

PMID- 9257183
TI  - Controlled release of cytarabine from poly(2-hydroxyethyl methacrylate-co-N-vinyl
      2-pyrrolidone) hydrogels.
AB  - Controlled release of cytarabine (ara-C) from poly(2-hydroxyethyl methacrylate-co
      N-vinyl-2-pyrrolidone) [p(HEMA-co-VP)] hydrogels cross-linked with ethylene
      glycol dimethacrylate (EGDMA) is reported. Three compositions of copolymer, each
      one with a different cross-linking degree, have been studied: H50/VP50, H75/VP25,
      and H80/VP20. Ara-C (5-25 mg by disc) was trapped in the gels by including it in
      the polymerization feed mixture. The ara-C release time was between 1 day from
      H50/VP50/E0.5 discs and 16 days from H80/VP20/E15 discs. In all cases there is a
      time period for which the drug release rate is constant.

PMID- 9257184
TI  - Morphological evidence for a different fibronectin receptor organization and
      function during fibroblast adhesion on hydrophilic and hydrophobic glass
      substrata.
AB  - A polyclonal antibody against the beta 1 subunit of the fibronectin (FN) receptor
      was used to mimic the early events of integrin receptor functioning to study the
      initial cellular processes during the organization of FN matrix on biomaterials.
      Hydrophilic glass and hydrophobic octadecylsilane (ODS) surfaces have been
      applied as models for different biocompatible materials. By immunofluorescence we
      could demonstrate that FN receptors organize on the dorsal cell surface of
      adhering fibroblasts in a specific linear pattern along with actin filaments, but
      only if the cells were attached to hydrophilic glass. In contrast, FN receptors
      were not reorganized on hydrophobic octadecylsilane (ODS). In parallel
      experiments, FN matrix formation after 72 h of incubation on the same substrata
      has been analyzed microscopically, and quantified by cell ELISA, in order to be
      further correlated with the integrin receptor functioning in contact with the
      biomaterials. It was found that FN structuring and the amount of FN matrix have
      been significantly diminished on ODS that was related to the observed changes in
      integrin receptor functioning. To learn more about the mechanism of this
      phenomenon, desorption of 125I-FN from these substrata was studied and found to
      be significantly decreased on hydrophobic ODS. As a consequence, FN receptor
      (function) might be arrested on the ventral cell surface, thus the important role
      of beta 1 integrins in the positional organization of the FN matrix may be
      disturbed. In light of these facts, antibody-induced clustering of FN receptor
      can be considered as a useful model for studying the early steps of FN matrix
      formation on biomaterials.

PMID- 9257185
TI  - Roles of p300, pocket proteins, and hTBP in E1A-mediated transcriptional
      regulation and inhibition of p53 transactivation activity.
AB  - The conserved region 1 and the extreme N-terminus of adenoviral oncoprotein E1A
      are essential for transforming activity. They also play roles in the interaction
      of E1A with p300/CBP and pRb and are involved in both transactivation and
      repression of host gene expression. It was reported recently that p53-mediated
      transactivation is specifically repressed by E1A and that p53-induced apoptosis
      can be protected by pRb. In this report, we investigated the roles of pRb and
      p300 in the N-terminus of E1A-mediated transcriptional regulation. We demonstrate
      here that p300 and pRb have no effect on DBD.1-70 transactivation and that
      overexpression of p300 or pRb failed to relieve the repression by E1A. Repression
      of p53 transactivation requires both the extreme amino terminus and CR1 but not
      CR2. This repressive activity of E1A specifically correlates with E1A's ability
      to bind p300 and TBP. On the other hand, E1A inhibited the transactivation
      activity of a fusion construct containing the DNA binding domain of yeast Gal4
      and the transactivation domain of p53. When p53 was contransfected with E1A,
      similar inhibition was found in Saos-2 cells that lack endogenous pRb and p53
      activity. Introduction of pRb into Saos-2 cells did not affect p53 transcription
      activity. E1A-mediated repression can be relieved be overexpression of either
      p300, hTBP, or-TFIIB but cannot be released by overexpression of pocket proteins.
      Our data suggest that p300/CBP and TBP but not the pocket proteins, pRb, p107,
      and pRb2/p130 are functional targets of E1A in transcriptional regulation and
      that p53 transactivation requires the function of the p300/TBP/TFIIB complex,
      thus delineating a new pathway by which E1A may exert its transforming activity.

PMID- 9257186
TI  - Granulocyte colony-stimulating factor-induced activation of protein kinase-C in
      myeloid cells.
AB  - Granulocyte colony stimulating factor (G-CSF) regulates survival, proliferation,
      differentiation, and activation of myeloid cells. It binds to a high affinity
      receptor (G-CSF-R) expressed on myeloid cells, for which the signal transduction
      mechanisms other than protein tyrosine kinase (PTK) activation have not been
      completely identified. We explored the potential involvement of protein kinase-C
      (PKC) in G-CSF-R signal transduction. In this report, we provide direct evidence
      of PKC activation by G-CSF-R. G-CSF treatment of peripheral blood neutrophils,
      granulocytic cell lines (HL-60, NFS-60, KG-1), and monocytic cell lines (WEHI
      3B,U-937) resulted in PKC activation. Chelerythrine chloride and HA-100, an
      isoquinolinesulfonamide derivative, the specific inhibitors of PKC, 1,2-Bis(2
      aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA), a chelator of
      intracellular calcium, and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl
      ester (TMB-8), an inhibitor of intracellular calcium release, blocked G-CSF
      induced PKC activation in HL-60 cells, and reduced CD11b upregulation in
      neutrophils, but did not affect ligand-binding or down-modulation of G-CSF-R.
      Methyl 2,5-dihydroxycinnamate (MDHC), a potent inhibitor of protein tyrosine
      kinases (PTK), also inhibited PKC activation in response to G-CSF treatment,
      suggesting that PKC activation may occur downstream of PTK activation. Our
      results demonstrate the involvement of PKC in G-CSF-R signal transduction, and
      suggest a common signaling pathway in myeloid cells of granulocytic and monocytic
      lineages.

PMID- 9257187
TI  - Characterization and localization of mitochondrial oligopeptidase (MOP) (EC
      3.4.24.16) activity in the human cervical adenocarcinoma cell line HeLa.
AB  - In this study we describe the partial purification and characterization of the
      HeLa cell oligopeptidase M or endopeptidase 3.4.24.16. The HeLa enzyme was
      isolated initially by its ability to hydrolyse a nonapeptide substrate (P9) which
      was cognate to the N-terminal cleavage site of preproTGF alpha. The enzyme was
      shown to be a metalloprotease as it was inhibited by Zn(2+)-chelating agents and
      DTT, and had an approximate molecular weight of 55-63 kD determined by gel
      filtration. Neurotensin, dynorphin A1-17 and GnRH1-9 were rapidly degraded by the
      enzyme while GnRH1-10 and somatostatin were not. Neurotensin was cleaved at the
      Pro10-Tyr11 bond, leading to the formation of neurotensin (1-10) and neurotensin
      (11-13). The K(m) for neurotensin cleavage was 7 microM and the Ki for the
      specific 24.16 dipeptide inhibitor (Pro-ile) was 140 microM which were similar to
      those observed from the human brain enzyme [Vincent et al. (1996): Brain Res
      709:51-58]. Through the use of specific antibodies, the purified HeLa enzyme was
      shown to be oligopeptidase M. This enzyme and its closely related family member
      thimet oligopeptidase were shown to co-elute during the isolation procedure but
      were finally separated using a MonoQ column. Oligopeptidase M is located mainly
      in mitochondria though it was detected on the plasma membrane in an inactive
      form. The results obtained demonstrate the first recorded instance of this enzyme
      in human tissue cultured cells, and raise the issue of its function therein.

PMID- 9257188
TI  - Expression of cellular genes in HPV16-immortalized and cigarette smoke condensate
      transformed human endocervical cells.
AB  - We studied the molecular mechanism of successive multistep cervical carcinogenic
      progression with our previously established in vitro model system. This system
      was composed of primary human endocervical cells (HEN), two lines of HEN
      immortalized by HPV16 and their counterparts subsequently malignantly transformed
      by cigarette smoke condensate (CSC). The expression was examined of diverse
      cellular genes associated with oncogenesis and senescence, especially for
      cervical cancer. Consistent results were seen for the pairs of immortalized and
      malignantly transformed lines. Immortalization of HEN by HPV16 resulted in
      enhanced expression of H-ras, c-myc, B-myb, p53, p16INK4 and PCNA mRNA; enhanced
      expression of p16 and PCNA proteins; decreased expression of WAF1/p21/Cip1/Sid1
      and fibronectin mRNA; and decreased p53 protein. On the other hand, the CSC
      transformed counterparts of HPV16-immortalized cells had up-regulated levels of B
      myb, p53 and WAF1 mRNA and p53 protein. Our results indicate that the
      differential activation or inactivation of multiple cellular genes is important
      for the immortalization, as well as the transformation, of human cervical cells.
      Further, we suggest that our in vitro model system is useful for investigating
      the molecular mechanism of multistep cervical carcinogenesis.

PMID- 9257189
TI  - Cell-type specific regulation of human interstitial collagenase-1 gene expression
      by interleukin-1 beta (IL-1 beta) in human fibroblasts and BC-8701 breast cancer
      cells.
AB  - Interleukin-1 beta (IL-1 beta) is a potent cytokine that stimulates interstitial
      collagenase-1 (matrix metalloproteinase-1; MMP-1). In this study, we compared the
      mechanism(s) by which IL-1 beta induces collagenase gene expression in two very
      different cells, normal human foreskin fibroblasts (HFFs) and an aggressive
      breast cancer cell line, BC-8701 cells. Northern analysis showed that the time
      course of collagenase induction was distinct in the two cells: although both
      cells expressed low levels of MMP-1 constitutively, addition of IL-1 beta
      increased MMP-1 mRNA in HFFs by 1 h and levels remained high over a 24-h period.
      In contrast, MMP-1 levels in IL-1 beta-treated BC-8701 cells did not increase
      until 4 h, peaked by 12 h and then declined. To analyze the transcriptional
      response, we cloned and sequenced more than 4,300 bp of the human MMP-1 promoter,
      and from this promoter clone, we prepared a series of 5'-deletion constructs
      linked to the luciferase reporter and transiently transfected these constructs
      into both cell types to measure both basal and IL-1 beta induced transcription.
      When both cell types were uninduced, promoter fragments containing less than
      2,900 bp gave only a minimal transcriptional response, while larger fragments
      showed increased transcriptional activity. With IL-1 beta treatment, significant
      responsiveness (P < 0.001) in HFFs was seen only with the larger fragments, while
      in the BC-8701 cells, all fragments were significantly induced with IL-1 beta.
      Finally, we found that IL-1 beta stabilized MMP-1 mRNA in normal fibroblasts, but
      not in BC-8701 breast cancer cells. We conclude that both the transcriptional and
      post-transcriptional regulation of MMP-1 gene expression by IL-1 beta is
      controlled by cell-type specific mechanisms, and we suggest that IL-1 induced MMP
      1 expression in tumor cells and in neighboring stromal cells may amplify the
      invasive ability of tumor cells.

PMID- 9257190
TI  - Characterization of a metalloproteinase: a late stage specific gelatinase
      activity in the sea urchin embryo.
AB  - We have partially purified and characterized an 87 kDa gelatinase activity
      expressed in later stage sea urchin embryos. Cleavage activity was specific for
      gelatin and no cleavage of sea urchin peristome type I collagen, bovine serum
      albumin or casein was detected. Magnesium and Zn2+ inhibited the gelatinase and
      Ca2+ protected against inhibition. Ethylenediamine tetracetic acid,
      ethylenebisoxyethylenenitriol tetraacetic acid and 1,10-phenanthroline were
      inhibitory, suggesting that the gelatinase is a Ca(2+)- and Zn(2+)-dependent
      metalloproteinase. No inhibition was detected with serine or cysteine protease
      inhibitors and the vertebrate matrix metalloproteinase (MMP) inhibitor,
      Batimastat, was also ineffective. The vertebrate MMP activator p
      aminophenylmercuric acetate was without effect. These results allow us to
      identify both similarities and differences between echinoderm and vertebrate
      gelatinases.

PMID- 9257191
TI  - Binding of SPAAT, the 44-residue C-terminal peptide of alpha 1-antitrypsin, to
      proteins of the extracellular matrix.
AB  - SPAAT (short piece of alpha 1-antitrypsin [AAT]), the 44-residue C-terminal
      peptide of AAT, was originally isolated from human placenta [Niemann et al.
      (1992): Matrix 12:233-241]. It was shown to be a competitive inhibitor of serine
      proteases [Niemann et al. (in press): Biochem Biophys Acta]. The binding of SPAAT
      to one or more proteins of the extracellular matrix (ECM) was initially suggested
      on the basis of its recovery from tissue residues following a series of
      extractions designed to remove easily solubilized proteins [Niemann et al.
      (1992): Matrix 12:233-241]. Our binding studies with the model ECMs, Matrigel and
      Amgel, suggested that SPAAT might be bound by a specific collagen type as well as
      one or more non-collagenous ECM proteins. Individual ECM components were screened
      for their ability to bind SPAAT. When the four commonly occurring fiber-forming
      collagens (types I, II, III, and V) were evaluated, type III was found to be
      preferred. In addition, although SPAAT bound to preformed type III collagen
      fibers in a concentration dependent fashion, it did not bind to type III collagen
      molecules undergoing fibril formation. This is consistent with a physiological
      mode of interaction between SPAAT and type III collagen in vivo. Of the non
      collagenous ECM macromolecules (laminin-1, fibronectin, entactin, and heparan
      sulfate) tested, laminin-1 was preferred. The binding of radiolabelled SPAAT to
      type III collagen and laminin-1 was competitively inhibited by unlabelled SPAAT
      as well as an unrelated protein, human serum albumin (HSA), to establish binding
      specificity. The kinetics of the release of the bound radiolabelled SPAAT were
      also examined to substantiate the non-covalent and reversible nature of this
      association. These results support the view that susceptible proteins of the ECM
      may actually be coated with SPAAT in vivo, possibly affording protection against
      inappropriate protease digestion.

PMID- 9257192
TI  - Differential effects of tamoxifen-like compounds on osteoclastic bone
      degradation, H(+)-ATPase activity, calmodulin-dependent cyclic nucleotide
      phosphodiesterase activity, and calmodulin binding.
AB  - We studied effects of calmodulin antagonists on osteoclastic activity and
      calmodulin-dependent HCl transport. The results were compared to effects on the
      calmodulin-dependent phosphodiesterase and antagonist-calmodulin binding
      affinity. Avian osteoclast degradation of labeled bone was inhibited
      approximately 40% by trifluoperazine or tamoxifen with half-maximal effects at 1
      3 microM. Four benzopyrans structurally resembling tamoxifen were compared: d
      centchroman inhibited resorption 30%, with half-maximal effect at approximately
      100 nM, cischroman and CDRI 85/287 gave 15-20% inhibition, and l-centchroman was
      ineffective. No benzopyran inhibited cell attachment or protein synthesis below
      10 microM. However, ATP-dependent membrane vesicle acridine transport showed that
      H(+)-ATPase activity was abolished by all compounds with 50% effects at 0.25-1
      microM. All compounds also inhibited calmodulin-dependent cyclic nucleotide
      phosphodiesterase at micromolar calcium. Relative potency varied with assay type,
      but d- and l-centchroman, surprisingly, inhibited both H(+)-ATPase and
      phosphodiesterase activity at similar concentrations. However, d- and l
      centchroman effects in either assay diverged at nanomolar calcium. Of benzopyrans
      tested, only the d-centchroman effects were calcium-dependent. Interaction of
      compounds with calmodulin at similar concentrations were confirmed by
      displacement of labeled calmodulin from immobilized trifluoperazine. Thus, the
      compounds tested all interact with calmodulin directly to varying degrees, and
      the observed osteoclast inhibition is consistent with calmodulin-mediated
      effects. However, calmodulin antagonist activity varies between specific
      reactions, and free calcium regulates specificity of some interactions. Effects
      on whole cells probably also reflect other properties, including transport into
      cells.

PMID- 9257193
TI  - CBP70, a glycosylated nuclear lectin.
AB  - Some years ago, a lectin designated CBP70 that recognized glucose (Glc) but had a
      stronger affinity for N-acetylglucosamine (GlcNAc), was first isolated from HL60
      cell nuclei. Recently, a cytoplasmic form of this lectin was described, and one
      82 kDa nuclear ligand was characterized for the nuclear CBP70. In the present
      study, the use of Pronase digestion and the trifluoromethanesulphonic acid (TFMS)
      procedure strongly suggest that the nuclear and the cytoplasmic CBP70 have a same
      23 kDa polypeptide backbone and, consequently, could be the same protein. In
      order to know the protein better and to obtain the best recombinant possible in
      the future, the post-translational modification of the nuclear and cytoplasmic
      CBP70 was analyzed in terms of glycosylation. Severals lines of evidence indicate
      that both forms of CBP70 are N- and O-glycosylated. Surprisingly, this
      glycosylation pattern differs between the two forms, as revealed by beta
      elimination, hydrazinolysis, peptide-N-glycosydase F (PNGase F), and TFMS
      reactions. The two preparations were analyzed by affinity chromatography on
      immobilized lectins [Ricinus communis-l agglutinin (RCA-I), Arachis hypogaea
      agglutinin (PNA), Galanthus nivalis agglutinin (GNA), and wheat germ agglutinin
      (WGA)] and by lectin-blotting analysis Sambucus nigra agglutinin (SNA), Maackia
      amurensis agglutinin (MAA), Lotus tetragonolobus (Lotus), succinylated-WGA, and
      Psathyrella velutina agglutinin (PVA)]. Both forms of CBP70 have the following
      sugar moities: terminal beta Gal residues, Gal beta 1-3 GalNAc, Man alpha 1-3
      Man, sialic acid alpha 2-6 linked to Gal or GalNAc; and sialic acid alpha 2-3
      linked to Gal. However, only nuclear CBP70 have terminal GlcNAc and alpha-L
      fucose residues. All these data are consistent with the fact that different
      glycosylation pattern found for each form of CBP70 might act as a complementary
      signal for cellular targeting.

PMID- 9257194
TI  - Transcriptional and posttranscriptional mechanisms of glucocorticoid-mediated
      repression of phosphoenolpyruvate carboxykinase gene expression in adipocytes.
AB  - Glucocorticoids exert pleiotropic effects, among which negative regulation of
      transcription has been recognized as of crucial importance. While glucocorticoids
      induce phosphoenolpyruvate carboxykinase (PEPCK) gene expression in liver cells,
      it represses gene activity in adipose cells. We used the 3T3-F442A adipocytes to
      analyze the underlying mechanisms in these cells, the synthetic glucocorticoid
      dexamethasone exerts a dominant repression either on basal or on beta-agonist
      stimulation of PEPCK gene expression. To determine whether glucocorticoid action
      required protein synthesis, we employed cycloheximide, anisomycin, and puromycin,
      three different translation inhibitors. None of these affected induction by
      isoprenaline or repression by dexamethasone of isoprenaline stimulation. In
      contrast, dexamethasone inhibitory action on basal PEPCK mRNA was totally
      prevented by the three translation inhibitors. Time courses of glucocorticoid
      action on basal and on induction by beta-agonist were similar. Half-maximal
      effect of dexamethasone on isoprenaline-induced PEPCK mRNA was obtained at about
      10 nM, a tenfold higher concentration than that observed for the reduction of
      basal mRNA. Using the transcription inhibitor DRB, we showed that dexamethasone
      did not alter mRNA half-life, while isoprenaline strongly stabilized mRNA. In a
      3T3-F442A stable transfectant bearing -2,100 base pairs of the PEPCK promoter
      fused to the chloramphenicol acetyltransferase (CAT) gene, isoprenaline
      stimulated CAT activity, whereas dexamethasone reduced basal and isoprenaline
      induced CAT expression. Hence, beta-agonists exert both transcriptional and
      posttranscriptional regulation, while glucocorticoid action is purely
      transcriptional. However, mechanisms of glucocorticoid repression of basal and of
      beta-agonist stimulation appear different.

PMID- 9257195
TI  - Rapid chondrocyte maturation by serum-free culture with BMP-2 and ascorbic acid.
AB  - In serum-containing medium, ascorbic acid induces maturation of prehypertrophic
      chick embryo sternal chondrocytes. Recently, cultured chondrocytes have also been
      reported to undergo maturation in the presence of bone morphogenetic proteins or
      in serum-free medium supplemented with thyroxine. In the present study, we have
      examined the combined effect of ascorbic acid, BMP-2, and serum-free conditions
      on the induction of alkaline phosphatase and type X collagen in chick sternal
      chondrocytes. Addition of either ascorbate or rhBMP-2 to nonconfluent cephalic
      sternal chondrocytes produced elevated alkaline phosphatase levels within 24-72
      h, and simultaneous exposure to both ascorbate and BMP yielded enzyme levels at
      least threefold those of either inducer alone. The effects of ascorbate and BMP
      were markedly potentiated by culture in serum-free medium, and alkaline
      phosphatase levels of preconfluent serum-free cultures treated for 48 h with
      BMP+ascorbate were equivalent to those reached in serum-containing medium only
      after confluence. While ascorbate addition was required for maximal alkaline
      phosphatase activity, it did not induce a rapid increase in type X collagen mRNA.
      In contrast, BMP added to serum-free medium induced a three- to fourfold increase
      in type X collagen mRNA within 24 h even in the presence of cyclohexamide,
      indicating that new protein synthesis was not required. Addition of thyroid
      hormone to serum-free medium was required for maximal ascorbate effects but not
      for BMP stimulation. Neither ascorbate nor BMP induced alkaline phosphatase
      activity in caudal sternal chondrocytes, which do not undergo hypertrophy during
      embryonic development. These results indicate that ascorbate+BMP in serum-free
      culture induces rapid chondrocyte maturation of prehypertrophic chondrocytes. The
      mechanisms for ascorbate and BMP action appear to be distinct, while BMP and
      thyroid hormone may share a similar mechanism for induction.

PMID- 9257196
TI  - State of methylation of the human osteocalcin gene in bone-derived and other
      types of cells.
AB  - DNA methylation is a general mechanism of controlling tissue-specific gene
      expression. Osteocalcin is a bone matrix protein whose expression is limited
      almost entirely to osteoblasts. We were interested in determining whether the
      state of methylation of the osteocalcin gene plays a role in its expression by
      studying human bone-derived (MG-63, U2-Os, SaOs-2) and other types (normal
      lymphocytes, A-498, Hep G2) of cells. Reverse transcription-polymerase chain
      reaction (RT-PCR) analysis revealed that osteocalcin mRNA production is
      stimulated by 1,25(OH)2D3 in MG-63 and induced in SaOs-2 but not in U2-Os
      osteoblast-like osteosarcoma cells. Genomic analysis of the human osteocalcin
      gene showed that the local surroundings of this single-copy gene are identical in
      all cell lines studied. Using an isoschizomeric pair of restriction enzymes and
      Southern analysis, we found that the osteocalcin gene is identically methylated
      in all three osteosarcoma cell lines. The same sites are also methylated in human
      normal lymphocytes and A-498 kidney cells, whereas the degree of methylation is
      higher in Hep G2 human hepatocellular carcinoma cells. Furthermore, the
      osteocalcin gene was identically protected against enzymatic digestion at the
      chromatin level in normal lymphocytes and in all cell lines studied. Induction of
      hypomethylation of DNA by 5-azacytidine treatment did not cause an induction of
      osteocalcin synthesis in these cell lines. On the contrary, it attenuated the
      induction by 1,25(OH)2D3 in MG-63 cells. In gel mobility shift assays, human
      vitamin D receptor and the AP-1 transcription factor bound to an unmethylated
      response element oligonucleotide of the osteocalcin gene with greater affinity
      than to an in vitro methylated response element. These results indicate that the
      in vivo methylation state of the osteocalcin gene at sites determined in this
      study does not correlate with the inducibility of this gene. Nevertheless, the in
      vitro results clearly indicated that hypomethylation of critical regions of the
      osteocalcin gene promoter is a potential mechanism influencing effective binding
      of specific nuclear factors and, consequently, gene expression.

PMID- 9257199
TI  - Does significant arterial hypoxemia alter vital signs?
AB  - STUDY OBJECTIVE: To determine the cardiovascular and respiratory effects of
      arterial hypoxemia in adult volunteers. DESIGN: Prospective, subject-controlled.
      SETTING: University-affiliated hospital. SUBJECTS: 16 awake, unsedated,
      unanesthetized adult volunteers. INTERVENTIONS: Inspired oxygen concentration
      (FIO2) was decreased in decrements to reduce pulse oximeter values to a range of
      95% to 90%, 89% to 85%, 84% to 80%, and 79% to 70%. MEASUREMENTS AND MAIN
      RESULTS: Heart rate (HR), blood pressure (BP), respiratory rate (RR), arterial
      blood pH, gas tensions, and oxyhemoglobin saturation were determined during
      normoxia and each level of oxyhemoglobin desaturation. FIO2 was reduced from 21%
      to 10%. Arterial blood oxyhemoglobin saturation and oxygen tension ranged from
      100% to 71% and 103 to 35 mmHg, respectively. There were no significant changes
      in RR, BP, or HR during the study. CONCLUSIONS: HR, BP, and RR are not reliable
      indicators of arterial hypoxemia in awake volunteers. If this finding is also
      true for sedated or anesthetized patients, then continuous monitoring with pulse
      oximetry should be used whenever patients are at risk for arterial hypoxemia.
      Stable HR, BP, and RR may not eliminate the possibility of significant arterial
      hypoxemia and impending catastrophic events.

PMID- 9257198
TI  - The utility of routine postoperative chest radiography in the postanesthesia care
      unit.
AB  - STUDY OBJECTIVE: To evaluate the clinical significance and cost effectiveness of
      routine chest radiographs in the postanesthesia care unit (PACU). DESIGN:
      Prospective study. SETTING: University hospital. PATIENTS: 100 patients who were
      admitted to the PACU following various surgical procedures, and in whom a
      postoperative chest radiograph was routinely performed. INTERVENTIONS: Chest
      radiograph was taken in each study patient soon after admission to the PACU. The
      indications for postoperative chest radiograph were: thoracotomy (30 patients),
      thoracoscopy (7), central vein catheterization (CVC) (75), pulmonary artery
      catheterization (3), and mechanical ventilation (36). A staff anesthesiologist
      examined each patient, evaluated each chest radiograph, and decided if a
      treatment action was to be taken. A chest radiologist later evaluated each chest
      radiograph, and her interpretation was compared with the anesthesiologist's
      interpretation to assess if this may affect patient management. MEASUREMENTS AND
      MAIN RESULTS: The anesthesiologist found eight abnormal chest radiographs (8%):
      three with pulmonary congestion, four in whom the CVC was in the right atrium,
      and one with malpositioned CVC. In four patients (4%), the chest radiographic
      findings directly affected patient management. The radiologist confirmed the
      anesthesiologist's interpretation and found four additional abnormalities: one
      pulmonary congestion, one malpositioned CVC, and two chest radiographs, each with
      a small pneumothorax. CONCLUSIONS: Abnormal chest radiographic findings resulted
      in a change in the management of only 4% of the patients. Therefore, the yield of
      a routine postoperative chest radiograph in the PACU is low. Performing a chest
      radiograph for a specific indication rather than on a routine basis, may decrease
      work load and save expenses. Postoperative chest radiography can be safely
      evaluated by a staff anesthesiologist.

PMID- 9257197
TI  - Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal
      proliferation of a variety of cancer cells but have differing molecular effects.
AB  - The seco-steroid hormone, 1 alpha, 25 dihydroxyvitamin D3 (1 alpha,25(OH)2D3)
      binds to a specific nuclear receptor that acts as a ligand-inducible
      transcription factor. The resulting genomic effects include partial arrest in
      G0/G1 of the cell cycle and induction of differentiation; these effects have been
      observed in various types of cancer. Recently, we produced enzymatically the
      natural 24-oxo metabolites of 1 alpha,25(OH)2D3 and two of its potent synthetic
      analogs (1 alpha,25-(OH)2-16-ene-D3 and 1 alpha,25-(OH)2-20-epi-D3) using a rat
      kidney perfusion system. We have found that the 24-oxo metabolites of both 1
      alpha,25(OH)2D3 and its analogs have either the same or greater antiproliferative
      activity against various cancer cells as their parental compounds. Notably, two
      cell lines (DU-145 (prostate cancer) and MDA-MB-436 [breast cancer]) that were
      extremely resistant to the antiproliferative effects of vitamin D3 analogs
      displayed greater sensitivity towards the 24-oxo metabolite of the vitamin D3
      analog. Similarly, the 24-oxo metabolites had the capacity to induce
      differentiation and apoptosis and to diminish the proportion of cells in S phase.
      Most interestingly, while the analog 1 alpha,25(OH)2-20-epi-D3 induced expression
      of BRCA1 in MCF-7 breast cancer cells; its 24-oxo metabolite dramatically
      suppressed BRAC1 expression. Thus, we have shown for the first time that the
      various biological activities produced by the hormone 1 alpha,25(OH)2D3 and some
      of its analogs may represent a combination of actions by the hormone 1
      alpha,25(OH)2D3 and its natural 24-oxo metabolites.

PMID- 9257200
TI  - The effect of intravenous ketorolac given intraoperatively versus postoperatively
      on outcome from gynecologic abdominal surgery.
AB  - STUDY OBJECTIVES: To examine the effect of timing of an intravenous (i.v.) dose
      (intraoperative vs. postoperative) of ketorolac tromethamine on pain scores and
      overall outcome after total abdominal hysterectomy (TAH) and myomectomy. DESIGN:
      Prospective, randomized, placebo-controlled study. PATIENTS: 248 ASA physical
      status I and II adult female patients scheduled for elective hysterectomy or
      myomectomy. INTERVENTIONS: General anesthesia was administered that consisted of
      thiopental sodium for induction, enflurane or isoflurane in nitrous oxide-oxygen
      for maintenance, and small doses of fentanyl and midazolam. Patients were
      randomized into three groups to receive toradol/placebo on a dosing schedule of
      dose 1 given one-half hour prior to expected end of surgery, dose 2 given on
      awakening in the postanesthesia care unit, and doses 3, 4, and 5 given at 6, 12,
      and 18 hours, respectively, after dose 2; Group 1 patients received placebo
      (saline) for dose 1, ketorolac 60 mg i.v. for dose 2, and ketorolac 30 mg i.v.
      for doses 3, 4, and 5. Group 2 patients received ketorolac 60 mg i.v. for dose 1,
      placebo for dose 2, and ketorolac 30 mg i.v. for doses 3, 4, and 5. Group 3
      patients received placebo for all doses. All patients were given i.v. morphine
      PCA postoperatively, and morphine usages, visual analog pain intensity (VAS)
      scores, as well as adverse events and median times to recovery milestones were
      recorded. MEASUREMENTS AND MAIN RESULTS: VAS scores (mean) before dose 2 were
      significantly lower in Group 2 than Group 1, as were at-rest evaluations at 15
      minutes and one hour. Group 2 patients also had decreased morphine requirements
      as compared to placebo. Both ketorolac groups (Groups 1 and 2) had significantly
      higher values for patient and observer overall ratings, case of nursing care, and
      tolerability as compared to placebo (Group 3). There were no significant
      differences among groups in adverse events or median times to recovery
      milestones. CONCLUSIONS: Although it is possible to demonstrate an improvement in
      early postoperative pain scores with intraoperative ketorolac and better overall
      ratings of ketorolac both intraoperatively and postoperatively as compared with
      placebo, the lack of clinically significant differences in analgesic efficacy in
      the two active study groups indicates the need for a careful consideration by the
      clinician of the risks versus benefits involved in the administration of
      antiplatelet medication in the perioperative period.

PMID- 9257201
TI  - Intravenous dolasetron mesilate in the prevention of postoperative nausea and
      vomiting in females undergoing gynecological surgery.
AB  - STUDY OBJECTIVE: To evaluate a range of doses of intravenous (i.v.) dolasetron
      mesilate, in preventing postoperative nausea and vomiting (PONV). DESIGN: Double
      blind, placebo-controlled, randomized, multicenter trial. SETTING: Ten hospitals
      and/or surgical centers. PATIENTS: 281 women undergoing gynecologic surgery with
      general anesthesia. INTERVENTIONS: Patients received one of four single, i.v.
      doses of dolasetron mesilate (12.5 mg, 25 mg, 50 mg, and 100 mg) or placebo
      administered following cessation of anesthesia. MEASUREMENTS AND MAIN RESULTS:
      Patients were monitored for 24 hours following study drug administration. The
      antiemetic efficacy of each dolasetron mesilate dose was evaluated by recording
      the number and timing of emetic episodes, and the effects on nausea were assessed
      by use of visual analog scales (VAS). Safety was assessed by adverse event
      reports, clinical laboratory tests, electrocardiographic (ECG) measurements, and
      monitoring vital signs. Complete responses (patients with no emetic episodes and
      no escape antiemetic medication requirements in 24 hours) were achieved by 54% in
      the 12.5-mg, 67% in the 25-mg, and 59% in both the 50-mg and 100-mg dolasetron
      mesilate dose groups, and by 43% in the placebo group. Nausea VAS assessments
      demonstrated that dolasetron-treated patients were significantly (p = 0.048) more
      likely to report no nausea (VAS score < 5 mm) than those in the placebo group.
      Adverse events reported generally were mild in intensity, and there were no
      clinically significant changes in laboratory tests, vital signs, or ECG
      parameters. CONCLUSIONS: Dolasetron was effective and well tolerated for the
      prevention of PONV in female patients undergoing gynecologic surgery with general
      anesthesia.

PMID- 9257202
TI  - Effects of anesthetic technique on side effects associated with fentanyl Oralet
      premedication.
AB  - STUDY OBJECTIVES: To evaluate the efficacy of 5 to 10 micrograms/kg of oral
      transmucosal fentanyl citrate (OTFC) as an anesthetic premedication, and to
      determine whether propofol induction reduces postoperative nausea and vomiting
      (PONV) in pediatric patients premedicated with OTFC undergoing outpatient
      surgery. DESIGN: Prospective, randomized, double-blinded study. SETTINGS:
      University of Michigan Health Care Systems and University of Arizona.
      PARTICIPANTS: 62 ASA physical status I and II children aged 4 to 14 years (8.9 +/
      0.5 years). INTERVENTIONS: Subjects were randomly assigned to one of four
      groups: (1) OTFC premedication and halothane induction; (2) OTFC premedication
      and propofol induction; (3) placebo premedication and halothane induction; and
      (4) placebo premedication and propofol induction. OTFC or placebo was
      administered 30 minutes prior to induction, and activity (sedation),
      apprehension, and cooperation scores were recorded before, at 15 and 30 minutes
      after study drug, and on induction. All perioperative adverse events were
      recorded. MEASUREMENTS AND MAIN RESULTS: Children who received OTFC became
      drowsier and had a significant change from baseline in combined activity,
      apprehension, and cooperation scores, whereas those who received placebo became
      less cooperative at induction. Patients who received OTFC experienced more
      adverse events overall (p < 0.001) than patients who received placebo.
      Additionally, OTFC patients experienced more vomiting (p < 0.001) and pruritus (p
      = 0.049) than controls. The incidence of PONV in patients who received OTFC and
      halothane induction was 50%, compared to 30% in patients receiving OTFC and a
      propofol induction (p = NS). CONCLUSIONS: OTFC in doses of 5 to 10 micrograms/kg
      was effective in producing sedation and facilitating cooperation with induction;
      however, it was associated with significant PONV in our study. Although propofol
      induction did not significantly reduce PONV in our study, further study with a
      larger sample, and with propofol as the sole anesthetic, may be warranted.

PMID- 9257203
TI  - Double-blind comparison of two doses of rocuronium and succinylcholine for rapid
      sequence intubation.
AB  - STUDY OBJECTIVE: To compare the pharmacodynamics of two commonly recommended
      doses of rocuronium bromide (0.7 mg/kg and 0.9 mg/kg) and succinylcholine (1.5
      mg/kg) when used for rapid-sequence intubation. DESIGN: Prospective, double
      blind, randomized study. SETTING: Operating rooms at a university hospital.
      PATIENTS: 45 ASA physical status I and II adult patients scheduled for elective
      surgeries under general anesthesia. INTERVENTIONS: Nonpremedicated patients were
      anesthetized with fentanyl 2 mcg/kg followed by thiopental sodium 4 to 5 mg/kg
      and muscle relaxant using rapid-sequence technique. Group 1 (n = 15) received
      rocuronium bromide 0.7 mg/kg. Group 2 (n = 16) received rocuronium bromide 0.9
      mg/kg, and Group 3 (n = 14) received succinylcholine 1.5 mg/kg. Intubation was
      performed 60 seconds after the administration of muscle relaxant. MEASUREMENTS
      AND MAIN RESULTS: The case of intubation was scored using a scale of 1 to 4.
      Blood pressure and heart rate were measured beginning one minute before induction
      of anesthesia up to 5 minutes after intubation. Intubation scores were similar in
      groups 2 and 3 and were noted as good or excellent in all patients. Group 1
      displayed a significantly lower intubation score than the other two groups; 60%
      were rated as poor. No significant differences in hemodynamic data were seen
      among the three groups. CONCLUSIONS: Rocuronium bromide at a dose of 0.9 mg/kg
      provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute.
      Intubating conditions at 1 minute following a 0.7 mg/kg dose of rocuronium are
      not as good as those following a 0.9 mg/kg dose of rocuronium or a 1.5 mg/kg dose
      of succinylcholine.

PMID- 9257205
TI  - Detection of myocardial ischemia by transesophageal echocardiographically
      determined changes in left ventricular area in patients undergoing coronary
      artery bypass surgery.
AB  - STUDY OBJECTIVE: To evaluate left ventricular (LV) dimensions and function during
      myocardial ischemic episodes in anesthetized patients undergoing coronary artery
      bypass surgery. DESIGN: Prospective, nonrandomized study. SETTING: Large, medical
      school-affiliated tertiary-care medical center. PATIENTS: 36 adults undergoing
      elective primary coronary artery bypass surgery. INTERVENTIONS: Transesophageal
      atrial pacing for 3 to 5 minutes at heart rates (HRs) of 65, 70, 80, and 90 beats
      per minute. MEASUREMENTS AND MAIN RESULTS: Arterial, pulmonary artery, and venous
      pressures, transesophageal echocardiographic (TEE) determined LV end-diastolic
      (EDA) and end-systolic (ESA) areas, and fractional area change (FAC = [FDA
      ESA]/EDA). Myocardial ischemia determined as at least 1 mm ST segment deviation
      at J + 60 milliseconds from 12-lead electrocardiography (ECG) and TEE detected
      new LV regional wall motion abnormalities. Biplane TEE images were recorded on
      videotape, and LV EDA and ESA were determined with planimetry from images of the
      LV short axis. Myocardial ischemia was observed in 12 patients. In these
      patients, EDA and ESA were higher and FAC lower than those patients without
      ischemia at the same HR. There were no differences between patients with and
      without myocardial ischemia with regard to pulmonary artery occlusion pressure,
      stroke volume, or other hemodynamic variables. The positive predictive values
      were best for ESA (67%) and EDA (58%), and least for FAC (18%). Negative
      predictive values were highest for ESA (85%) and EDA (80%), and least for FAC
      (47%). CONCLUSIONS: In anesthetized patients undergoing coronary artery bypass
      surgery, myocardial ischemia observed during atrial pacing results in increases
      in LV dimensions and decreases in FAC compared with values in patients without
      ischemia. These results support further investigations of the clinical usefulness
      of monitoring LV EDA and LV ESA with TEE as a method of myocardial ischemia
      detection.

PMID- 9257204
TI  - Clinical analysis of the flexor hallucis brevis as an alternative site for
      monitoring neuromuscular block from mivacurium.
AB  - STUDY OBJECTIVES: To compare the flexor hallucis brevis, which is responsible for
      flexion of the great toe, to the adductor pollicis as a site for monitoring the
      onset and recovery from neuromuscular block after an intubating dose of
      mivacurium chloride. DESIGN: Prospective patient-controlled study. SETTING:
      University teaching hospital. PATIENTS: 10 ASA physical status I and II adults
      (age 18 to 55 years, 6 women, 4 men) scheduled for elective procedures requiring
      muscle relaxation for tracheal intubation. MEASUREMENTS AND MAIN RESULTS:
      Patients were monitored at the adductor pollicis and the flexor hallucis brevis
      during the onset and recovery of neuromuscular block, which was administered to
      facilitate tracheal intubation. All subjects were given mivacurium 0.2 mg/kg over
      30 seconds. Their train-of-four (TOF) response was continually monitored at both
      sites until the patient recovered from the intubating dose to a TOF ratio of
      0.75. The time to onset of neuromuscular block, recovery of the first TOF
      response, and recovery to a TOF ratio of 0.75 were compared between the two
      monitoring sites using the Wilcoxon signed rank test. Following administration of
      the intubating dose of mivacurium, the loss of all twitch response occurred 1.2
      minutes sooner at the adductor pollicis than at the flexor hallucis brevis (p <
      0.02). Reappearance of the first twitch occurred 0.49 minutes slower at the
      adductor pollicis, although this difference was not statistically significant.
      The time to recovery to a TOF ratio of 0.75 at the adductor pollicis was slower
      by 2.83 minutes (p = 0.046). CONCLUSIONS: Due to its lag behind the adductor
      pollicis, the flexor hallucis brevis is not a good indicator of when to intubate
      the trachea during the onset of neuromuscular block; however, its faster recovery
      may make it useful for monitoring deep neuromuscular block intraoperatively or
      during recovery when the adductor pollicis TOF response still shows complete
      blockade.

PMID- 9257206
TI  - Lidocaine in the endotracheal tube cuff reduces postoperative sore throat.
AB  - STUDY OBJECTIVES: To test the hypothesis that continuous application of local
      anesthesia at the contact area between the endotracheal tube cuff and trachea
      would reduce both the incidence and severity of postoperative sore throat by
      blocking the tracheal pain receptors with local anesthetic delivered via
      endotracheal tube (ETT) cuff. DESIGN: Double-blind randomized study. SETTING:
      University affiliate hospital. PATIENTS: 106 ASA physical status I and II
      patients. INTERVENTIONS: Patients' ETT cuffs were inflated with either air or
      lidocaine. The cuffs of the lidocaine group were prefilled with lidocaine for 90
      minutes prior to intubation to saturate the cuff membrane. One hour and 24 hours
      following extubation, patients were asked about the presence and severity of
      postoperative sore throat. MEASUREMENTS AND MAIN RESULTS: There was no difference
      between groups in demographics or anesthetic management. The incidence of sore
      throat was significantly different at the 24-hour evaluation (59% air vs. 32%
      lidocaine, p = 0.01). Severity of sore throat was significantly worse with air at
      both evaluation periods (1 hour = 18.7 +/- 27.0 air vs. 7.90 +/- 18.1 lidocaine,
      p = 0.02; 24 hours = 25.6 +/- 27.5 air vs. 14.5 +/- 24.8 lidocaine, p = 0.03).
      CONCLUSIONS: Using lidocaine to inflate the ETT cuff decreases the severity of
      postoperative sore throat at one hour, and both the incidence and severity at 24
      hours.

PMID- 9257207
TI  - Nausea and vomiting following thyroid and parathyroid surgery.
AB  - STUDY OBJECTIVES: To determine the incidence of postoperative nausea and vomiting
      (PONV) following thyroid and parathyroid surgery. To determine whether PONV is
      reduced when propofol is used for maintenance of anesthesia as compared to
      isoflurane and to evaluate the costs and resource consumption associated with
      these two anesthetic regimens. DESIGN: Randomized, prospective study. SETTING:
      University-affiliated hospital--a referral center for endocrinologic surgery.
      PATIENTS: 118 ASA physical status I and II patients, aged 18 years and older,
      undergoing elective thyroid or parathyroid surgery. INTERVENTIONS: Patients
      received either isoflurane (0.5 to 1.3% end-tidal) or propofol (50 to 200
      micrograms/kg/min) for maintenance of anesthesia. All patients received propofol
      for induction of anesthesia, succinylcholine or vecuronium, nitrous oxide, and
      fentanyl. Prophylactic antiemetics were not administered. Postoperative pain was
      treated with ketorolac, fentanyl, or acetaminophen. MEASUREMENTS AND MAIN
      RESULTS: Signs and symptoms of nausea and vomiting were graded on a four point
      scale as 1 = no nausea; 2 = mild nausea; 3 = severe nausea; 4 = retching and/or
      vomiting. Grades 3 and 4 were grouped together as PONV. The combined incidence of
      PONV was 54% over the 24-hour postoperative evaluation period. PONV was
      significantly more common in patients receiving isoflurane than propofol for
      maintenance of anesthesia (64% vs. 44%). In women (n = 87), the incidence of PONV
      was significantly greater in those patients who received isoflurane than those
      who received propofol for maintenance (71% vs. 42%). However, in men (n = 31),
      there was no significant difference in PONV between anesthetic regimens (47% with
      isoflurane vs. 50% with propofol). There were no differences in the duration of
      stay in the postanesthesia care unit, time to discharge from the hospital, or
      local wound complications (hematomas) between groups. The use of propofol for
      maintenance of anesthesia was associated with an additional cost, relative to the
      isoflurane group, of $54.26 per patient. CONCLUSION: Patients undergoing thyroid
      or parathyroid surgery are at high risk for the development of PONV. Propofol for
      maintenance of anesthesia, although more expensive than isoflurane, reduces the
      rate of PONV in women.

PMID- 9257208
TI  - Negative pressure pulmonary edema after acute upper airway obstruction.
AB  - STUDY OBJECTIVES: To review the clinical characteristics and the pathogenesis of
      negative pressure pulmonary edema, and to determine its incidence in surgical
      patients. DESIGN: Retrospective case-report study. SETTING: Operating room,
      postanesthesia care unit and surgical intensive care of a teaching hospital.
      PATIENTS: 30 surgical adult ASA physical status I, II, III, IV, and V patients
      who suffered from negative pressure pulmonary edema during the period 1992-1995.
      MEASUREMENTS AND MAIN RESULTS: This study showed a rapid onset of negative
      pressure pulmonary edema after acute upper airway obstruction, due mainly to
      laryngospasm in the postoperative period and to upper airway pathology in the
      preoperative period. Negative pressure pulmonary edema appeared more frequent in
      healthy (ASA physical status I and II), middle-aged and male patients, with a
      general incidence of 0.094%. The resolution was relatively rapid after
      reestablishment of the airway, adequate oxygenation, and positive airway pressure
      application. The clinical course was uncomplicated in all the patients.
      CONCLUSIONS: In this study, negative pressure pulmonary edema presented a
      relatively high incidence. Prevention, early diagnosis, and prompt treatment
      allowed a rapid and uncomplicated resolution.

PMID- 9257209
TI  - Transfusion of platelet-rich plasma from the organ donor during cardiac
      transplantation.
AB  - STUDY OBJECTIVE: To evaluate whether transfusion of platelet-rich plasma from the
      organ donor during cardiac transplantation can influence the amount of the needed
      homologous blood products. DESIGN: Randomized, controlled study. SETTING:
      University hospital. PATIENTS: 16 ASA physical status III patients undergoing
      orthotopic cardiac transplantation. INTERVENTIONS: Eight patients received donor
      plasma, while another 8 patients served as a control group. Blood from the organ
      donor was acquired during cardiac explantation. Thereafter platelet-rich plasma
      was separated by plasmapheresis (2400 turns per minute). The plasma was then
      transfused to the organ recipient at the end of the cardiac transplantation. The
      control group received a similar amount of albumin 5%. MEASUREMENTS AND MAIN
      RESULTS: In the patients who received donor plasma, the platelet count increased
      significantly from 98,000 +/- 49,000 mm-3 to 123,000 +/- 55,000 mm-3, the
      postoperative requirement of packed red blood cells (PRBCs) was 5.8 +/- 4.5
      units, which was significantly lower as compared to the control group (10.8 +/-
      5.9 units). CONCLUSIONS: Transfusion of platelet-rich plasma from the organ donor
      to the recipient was confirmed to be feasible, the number of postoperatively
      transfused PRBCs was reduced.

PMID- 9257211
TI  - Acute tachyphylaxis to propofol sedation during ethanol withdrawal.
AB  - We treated a patient with a 30-year history of ethanol and benzodiazepine abuse
      who, on emerging from general anesthesia, was combative and confused. Our working
      diagnosis was acute ethanol withdrawal, and the patient received intravenous
      (i.v.) propofol, and midazolam. Initially small doses (10 to 20 mg) of propofol,
      combined with a midazolam infusion (50 mg/hr), produced sedation. Later, however,
      the patient became increasingly combative, confused, hypertensive, and
      tachycardic despite an i.v. propofol infusion at doses up to 1,000
      micrograms/kg/min (total propofol dose: 1,755 mg). Immediate sedation was
      produced by thiopental bolus (500 mg) and i.v. infusion (200 mg/hr). The
      implication of the patient's initial appropriate response to propofol, followed
      by the lack of effect when much higher doses were employed, is discussed. While
      tachyphylaxis has been reported after long-term propofol use, we believe this to
      be the first case of acute tachyphylaxis.

PMID- 9257210
TI  - Effects of intrathecal opioid on extubation time, analgesia, and intensive care
      unit stay following coronary artery bypass grafting.
AB  - STUDY OBJECTIVE: To determine if intrathecal opioid decreases time to extubation
      after coronary artery bypass surgery without compromising postoperative
      analgesia. DESIGN: Prospective randomized trial. SETTING: Veterans Affairs
      Hospital. PATIENTS: 21 ASA physical status III and IV men scheduled for elective
      coronary bypass surgery, who had not received medications that would impair
      anticoagulation at the time of surgery. INTERVENTIONS: Patients were randomized
      to receive 10 micrograms/kg morphine and 25 micrograms fentanyl intrathecally
      preoperatively (n = 12) or no intrathecal opioid (n = 9). The latter group
      received 25 to 50 micrograms/kg fentanyl and 0.05 to 0.1 mg/kg midaxolam
      intraoperatively, whereas the intrathecal opioid group received intravenous
      (i.v.) fentanyl and midazolam only as needed. Both groups were administered i.v.
      morphine and midazolam postoperatively as needed by intensive care unit (ICU)
      personnel who were blinded to the treatment group. MEASUREMENTS AND MAIN RESULTS:
      For the first 24 hours postoperatively, pain levels (0 = none, to 10 = most
      severe) and sedation levels (1 = none, to 5 = unconscious) were measured hourly.
      The time to extubation and discharge from the ICU was recorded. ECG evidence of
      myocardial ischemia was noted. Pain scores were low for both groups (1.5), but
      the intrathecal opioid subjects exhibited less sedation than the high-dose
      fentanyl subjects [means +/- standard deviation (SD) of 2.3 +/- 0.4 vs. 2.8 +/-
      0.5, p = 0.03]. Extubation time was 12 hours shorter in the intrathecal opioid
      group (2.9 +/- 5.3 vs. 14.7 +/- 6.8, p = 0.001). The five subjects with a one day
      ICU stay were all in the intrathecal opioid group (p = 0.04). The incidence of
      myocardial ischemia did not differ between the two groups. CONCLUSIONS:
      Intrathecal opioid can facilitate early extubation and discharge from the ICU
      without compromising analgesia or increasing myocardial ischemia.

PMID- 9257212
TI  - Accidental shock during epidural anesthesia in a patient with NSAID-induced
      hyporeninemic hypoaldosteronism.
AB  - An obese man suffered cardiac arrest twenty minutes after receiving epidural
      anesthesia for incision and debridement of wound over the right leg. The
      patient's condition stabilized after emergent cardiopulmonary resuscitation. It
      was found that the patient had been self-administering an herbal drug
      continuously for a year and a half, and that this drug contained ethoxybenzamide,
      which is a nonsteroidal anti-inflammatory drug (NSAID). Low plasma renin and
      aldosterone levels were noted from the blood sample taken at the time of the
      cardiac arrest. The cardiac arrest was believed to be related to NSAID-induced
      hyporeninemic hypoaldosteronism, superimposed with epidural anesthesia-induced
      sympathectomy.

PMID- 9257214
TI  - A simple method of assessing neurologic motor power of patients during carotid
      endarterectomy.

PMID- 9257213
TI  - Compartment syndrome of the upper arm after pressurized infiltration of
      intravenous fluid.
AB  - Perioperative management of the acute trauma patient requires constant
      surveillance for the unexpected. We describe a case of upper extremity
      compartment syndrome resulting from pressurized infusion of crystalloid through
      an intravenous catheter placed in the emergency ward. Early recognition,
      diagnosis, and intervention with surgical fasciotomy averted potential
      complications and morbidity.

PMID- 9257215
TI  - Laryngeal mask airway longevity and pilot-balloon failure.

PMID- 9257216
TI  - Longer tube length eases endotracheal intubation via the laryngeal mask airway in
      infants and children.

PMID- 9257217
TI  - Does general anesthesia for dilation and curettage cause more perioperative
      bleeding?

PMID- 9257218
TI  - Development of a suboutcome strategy to measure interpersonal process in
      psychotherapy from an observer perspective.
AB  - Based on increasing recognition that the therapeutic relationship is critical in
      psychotherapy, the goal of this study was to establish the psychometric
      properties of a suboutcome strategy that could identify important in-session
      events involving patient-therapist interactions. Ten third-party observers were
      calibrated on a circumplex measure of suboutcome, a shortened version of the
      Wiggins' Interpersonal Adjective Scale-Revised. These observers rated four
      sessions from each of 28 cases of short-term psychotherapy. Each session was
      rated by thirds and selected to represent each quartile of a 40-session treatment
      protocol. The major findings indicated adequate interrater reliability and
      evidence for criterion validity that suggested a predictive relationship of
      patient and therapist affiliation to ultimate outcome, especially as observed
      early in treatment.

PMID- 9257219
TI  - Use of subtle and obvious scales to detect faking on the MCMI-II.
AB  - Subtle and obvious MCMI-II items were identified using ratings of item subtlety
      by 103 college students. Another group of 304 students completed the MCMI-II
      under instructions to answer honestly or to fake their appearance. An index of
      differential endorsement of subtle and obvious items (S-O) was significantly
      correlated with the Desirability and Debasement validity scales. S-O was about as
      successful as the three MCMI-II validity scales in discriminating between
      subjects who answer honestly and who fake their appearance. Although S-O is
      related to the MCMI-II validity scales, it appears to add to the ability of these
      scales to identify subjects who attempt to fake their profile.

PMID- 9257220
TI  - The application of computerized content analysis of speech to the diagnostic
      process in a psychiatric outpatient clinic.
AB  - Twenty-five new psychiatric outpatient were clinically evaluated and were
      routinely administered a brief psychological screening battery which included
      measures of symptoms, personality, and cognitive function. Included in this
      assessment procedure were the Gottschalk-Gleser Content Analysis Scales on which
      scores were derived from five-minute speech samples by means of an artificial
      intelligence-based computer program. Intercorrelations of these content analysis
      measures with scores obtained from the MMPI-2, SCL90, and other measures
      confirmed previously published construct validation findings. The use of this
      computerized content analysis procedure for initial, rapid diagnostic
      neuropsychiatric appraisal is supported by this research.

PMID- 9257221
TI  - Validity and reliability of Structured Interview for Competency Incompetency
      Assessment Testing and Ranking Inventory.
AB  - The Structured Interview for Competency and Incompetency Assessment Testing and
      Ranking Inventory (SICIATRI) is a structured interview guide to assess the
      competency for giving informed consent to treatment among psychiatric and medical
      patients. The competency levels of 48 psychiatric and medical inpatients were
      assessed by SICIATRI. A relatively high- inter-rater reliability of the SICIATRI
      items (over half of the items had kappa > or = .60) and concurrent validity
      (sensitivity = .83, specificity = .67 as measured against the global judgement of
      competency rating by the attending physician) were obtained. In addition to its
      brevity (it takes about 20 minutes to complete), these findings may warrant
      application of this instrument in a clinical setting.

PMID- 9257223
TI  - BPRS syndrome scales during the course of an episode of psychiatric illness.
AB  - This report examines changes in symptom levels on the four major syndrome scales
      from the Brief Psychiatric Rating Scale (BPRS): thought disturbance, paranoid
      disturbance, anxiety/depression, and emotional withdrawal/motor retardation.
      Baseline BPRS ratings were obtained during the first week of hospitalization for
      an acute episode of psychiatric illness, in 120 patients with schizophrenia,
      schizoaffective disorder, and depression. BPRS ratings were carried out in the
      week prior to discharge. Findings indicated that patients with schizoaffective
      disorder showed a greater magnitude of general clinical improvement than
      schizophrenics, although both groups had comparable improvement on thought
      disorder from admission to discharge. Paranoid symptoms did not recover as
      completely among schizophrenics compared to schizoaffective disorder patients. As
      expected, anxiety and depression symptoms remitted most prominently among the
      depressed inpatients.

PMID- 9257222
TI  - Factor structure of the expanded Brief Psychiatric Rating Scale.
AB  - This study investigated the factor structure of the expanded Brief Psychiatric
      Rating Scale (BPRS) on a sample of severe mentally ill homeless individuals. A
      confirmatory factor analysis using the Oblique Multiple Group method supported
      the typical five factor solution found in previous studies with the original
      BPRS. The five factors were labeled Thinking Disorder. Withdrawal. Anxiety
      Depression, Hostility-Suspicion, and Activity. Alpha coefficients for four of the
      scales ranged from .73 to .81; however, the alpha coefficient for the Hostility
      Suspicion scale was only .49.

PMID- 9257224
TI  - Measuring psychological distress in candidates for liver transplantation: a pilot
      study.
AB  - A protocol to evaluate the psychopathology of candidates for orthotopic (whole
      organ) liver transplantation (OLTX) is presented. Patients being considered for
      OLTX at the VA Pittsburgh Healthcare System were routinely referred for
      psychological evaluation consisting of a clinical interview and battery of
      standardized tests. The findings on 26 patients corroborate previous reports of
      psychological distress among transplant candidates. There is also evidence that
      higher levels of disturbance are observed among patients with a positive history
      of substance abuse. This study supports the value of standardized testing in the
      transplant population and suggests directions for further research.

PMID- 9257225
TI  - Comparison of two computational formulas for a WAIS-R seven subtest short form.
AB  - Several validity studies for a seven subtest WAIS-R short form have been
      conducted with patients from different populations as participants. All of these
      studies demonstrated high correlations between the short form IQ estimates and
      the actual VIQs, PIQs, and FSIQs (i.e., .90 to .98). In general, there also were
      small mean differences in the short form versus actual IQs across samples. There
      currently are two computational formulas for the seven subtest short form. The
      original weighted formula and a revised proration formula. This study
      investigated the accuracy of the two short form computational formulas in samples
      of patients with brain impairment. It was found that the two formulas produced
      nearly identical results from both statistical and clinical perspectives. Given
      that the formulas produce nearly identical results and the majority of published
      studies with this short form have used the weighted formula, we recommend that
      future investigators use the original weighted formula to maintain clinical and
      scientific consistency.

PMID- 9257227
TI  - Criterion-related diagnostic validity and test-retest reliability of the MMPI
      168(L) in mentally retarded adolescents and adults.
AB  - Sixty-three persons residing in an institution and diagnosed with mild or
      moderate mental retardation were assessed with a modification of the MMPI-168.
      Fifty-one of the residents also had psychiatric disturbances. The residents were
      divided into three categories on the bases of pre-existing DSM III-R diagnoses.
      The categories were "psychotic," "executive control dysfunction," and "other
      control." Significant differences were observed between the psychotic group and
      the other-control group on scales F, K, 6, and 8. Reevaluations were conducted
      four to 22 months later (MDN = 12 months). Significant test-retest reliability
      was found with scales L, F, K, 1, 4, 5, 6, 7, 8, and 9. The MMPI-168(L) can serve
      as an objective instrument in the assessment of thought disturbance and
      personality in mentally retarded persons.

PMID- 9257226
TI  - A combined rationally-empirically developed Variable Response Scale for detecting
      the random response set in the Jesness Inventory.
AB  - A Variable-Response Scale (VR) was developed for detecting randomness in the
      Jesness Inventory. Item pairs addressing similar content areas were identified.
      Pairs which showed endorsement frequencies of 5% or less in the scale development
      sample (250 males, 250 females) were included. Effectiveness was assessed by
      comparing 250 all-random and 250 part-random computer-generated protocols with
      those of honest subjects from a sample of 293 male delinquents classified as
      honest or not honest based on a matched-pair MMPI-A. VR was found to be very
      effective. Sensitivity, specificity, and other statistics were reported. Race
      differences were significant but very small. Younger children showed more
      inconsistency than older children. Age-based modified t-score norms were
      developed (1138 male, 358 female delinquents, ages 13-18).

PMID- 9257228
TI  - The MAACL-R6 with an adult clinical sample.
AB  - To determine the usefulness of the MAACL-R6 (sixth grade reading level version of
      the Multiple Affect Adjective Check List-Revised), its characteristics were
      studied in an adult clinical sample. As with the rescored samples, acceptable
      reliability and validity with this clinical sample was found. Also, the MAACL-R
      rescored on the sixth grade adjectives was equivalent in reliability and validity
      to the MAACL-R6 in this clinical sample, indicating that there was no context
      effect produced by being imbedded in the larger list of adjectives.

PMID- 9257229
TI  - Evaluating the diagnostic interview: obstacles and future directions.
AB  - The diagnostic interview plays a prominent role within the field of clinical
      psychology and occupies a fundamental component in graduate training. Educators
      seem to be focusing less on objective measures to evaluate student skill
      performance and the overall quality of the interview. The authors review the
      current methods for evaluating the diagnostic interview in psychology training
      and identify some of the major obstacles in accurately assessing student
      interview proficiency. Recommendations are made to address these difficulties,
      and the authors note some promising future directions.

PMID- 9257230
TI  - The alternate forms of the Positive and Negative Mood Scales: reliability,
      validity, and equivalence in referred samples.
AB  - The reliability (internal consistency and alternate form) of the trait version of
      the Positive and Negative Mood Scales in referred samples was found to be high,
      and the concurrent and discriminate validity was found to be moderate. As
      expected, means of the Positive Mood Scales were significantly higher in
      nonreferred samples and means of the Negative Mood Scales were significantly
      higher in referred samples. The alternate forms for each scale were equivalent.
      The Positive and Negative Mood Scales seem to be ready for use in research.

PMID- 9257231
TI  - Expanded norms for the Controlled Oral Word Association Test.
AB  - The Controlled Oral Word Association Test (COWAT) is a measure of a person's
      ability to make verbal associations to specified letters (i.e., C, F, and L).
      This measure is a useful component of a neuropsychological battery as it is able
      to detect changes in word association fluency often found with various disorders.
      In order to generate current norms for the elderly and aid in interpreting their
      performance, the COWAT was administered to a group of community-dwelling elderly
      persons. Information regarding total numbers of words produced as well as
      frequency of perseverations, breaking set, using the same word stem, and using a
      proper noun is provided.

PMID- 9257232
TI  - Phase maintenance in the pyloric pattern of the lobster (Panulirus interruptus)
      stomatogastric ganglion.
AB  - The extent to which individual neural networks can produce phase-constant motor
      patterns as cycle frequency is altered has not been studied extensively. I
      investigated this issue in the well-defined, rhythmic pyloric neural network.
      When pyloric cycle frequency is altered three- to fivefold, pyloric inter
      neuronal delays shift by hundreds to thousands of msec, and all pyloric pattern
      elements show strong phase maintenance. The experimental paradigm used is
      unlikely to activate exogenous inputs to the network, and these delay changes are
      thus likely to arise from phase-compensatory mechanisms intrinsic to the network.
      Pyloric inter-neuronal delays depend on the time constants of the network's
      synapses and of the membrane properties of its neurons. The observed delay shifts
      thus suggest that, in response to changes in overall cycle frequency, these
      constants vary so as to maintain pattern phasing.

PMID- 9257233
TI  - The pyloric pattern of the lobster (Panulirus interruptus) stomatogastric
      ganglion comprises two phase-maintaining subsets.
AB  - The pyloric pattern approximately maintains phase over a three- to fivefold
      frequency range when the pattern is defined by the pacemaker burst beginning.
      However, in this reference frame certain pattern elements maintain phase better
      than others, which suggests phase-maintaining subgroups might exist. Reanalysis
      of these data in reference frames defined by each element shows the pattern
      contains two groups of pattern elements within which phase is well maintained but
      between which maintenance is relatively poor. A third element shows intermediate
      maintenance with each group. If ventricular dilator neuron burst beginning (VDB)
      is chosen as pattern beginning, all members of one group occur early in the
      pattern, all members of the other occur late in the pattern, and the intermediate
      element occurs between the groups. Thus, at least for phase maintenance, VDB is a
      "natural" pyloric pattern beginning. These results suggest full description of
      complex patterns is best achieved by analysis in many reference frames.

PMID- 9257234
TI  - Multiday recordings from olfactory bulb neurons in awake freely moving rats:
      spatially and temporally organized variability in odorant response properties.
AB  - Chronic single-unit recordings were obtained from the mitral cell layer of the
      olfactory bulbs of awake freely moving rats placed in an odorant stream. Over
      periods up to five days, 618 recordings from 186 single neurons were obtained.
      Responses of individual neurons were found to be quite variable over time,
      although this variability was below chance and was not incremental. The responses
      of nearby neurons were more similar than expected by chance but less similar than
      individual neurons recorded at different times. However, responses of spatially
      well-separated neurons were more different than chance over short time periods.
      During rapid sniffing, single-unit responses became more variable, and the
      spatial organization of responses became less apparent. These results suggest
      that neuronal responses in the olfactory bulb are generally quite variable over
      time, with this variability increasing during periods of rapid sniffing. These
      results are interpreted in the context of a distributed, centrally modulated
      model of olfactory processing.

PMID- 9257235
TI  - Bifurcation, bursting, and spike frequency adaptation.
AB  - Many neural systems display adaptive properties that occur on time scales that
      are slower than the time scales associated with repetitive firing of action
      potentials or bursting oscillations. Spike frequency adaptation is the name given
      to processes that reduce the frequency of rhythmic tonic firing of action
      potentials, sometimes leading to the termination of spiking and the cell becoming
      quiescent. This article examines these processes mathematically, within the
      context of singularly perturbed dynamical systems. We place emphasis on the
      lengths of successive interspike intervals during adaptation. Two different
      bifurcation mechanisms in singularly perturbed systems that correspond to the
      termination of firing are distinguished by the rate at which interspike intervals
      slow near the termination of firing. We compare theoretical predictions to
      measurement of spike frequency adaptation in a model of the LP cell of the
      lobster stomatogastric ganglion.

PMID- 9257236
TI  - Helicobacter pylori induces an array of pro-inflammatory cytokines in human
      gastric epithelial cells: quantification of mRNA for interleukin-8, -1
      alpha/beta, granulocyte-macrophage colony-stimulating factor, monocyte
      chemoattractant protein-1 and tumour necrosis factor-alpha.
AB  - Despite the fact that Helicobacter pylori is known to be non-invasive, mucosal
      infiltration of inflammatory cells have been observed in the gastric mucosa. The
      exact pathogenesis of such an inflammatory reaction has not been well defined. We
      explored the repertoire of cytokine genes expressed in human gastric epithelial
      cells in response to coculture with H. pylori. After gastric epithelial cells,
      SNU-5 and KATO III, were infected with H. pylori, expression of several cytokine
      genes was assessed using quantitative reverse transcription polymerase chain
      reaction. Interleukin (IL)-8, -1 alpha and -1 beta mRNA were expressed in both
      gastric epithelial cells throughout the entire infection period. In SNU-5, IL-1
      alpha and IL-8 mRNA were expressed at 1 h, reached a peak level at 4 h and then
      decreased. Interleukin-1 beta mRNA was expressed less frequently than IL-1 alpha,
      or IL-8 mRNA. In SNU-5 cells, granulocyte-macrophage colony-stimulating factor
      (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor
      alpha (TNF-alpha) mRNA were expressed at 9 h, but was not expressed in KATO III.
      Gene expression paralleled the amount of IL-8 protein measured by enzyme-linked
      immunoabsorbent assay (ELISA). Interleukin-8 mRNA expression was not observed in
      KATO III cells infected with Campylobacter fetus ssp. fetus, Campylobacter jejuni
      or Escherichia coli. IL-8 mRNA expression was increased not only in gastric
      epithelial cells but also in non-gastric cells infected with H. pylori. These
      results suggest that an inflammatory reaction induced by H. pylori may be
      initially triggered by an array of pro-inflammatory cytokines expressed by
      infected gastric epithelial cells.

PMID- 9257237
TI  - Sucralfate attenuates gastric mucosal lesions and increased vascular permeability
      induced by ischaemia and reperfusion in rats.
AB  - Recent evidence suggests that oxygen-derived free radicals are involved in
      mediating gastric microvascular and parenchymal cell injuries induced by
      ischaemia and reperfusion. Therefore, the effect of the locally acting anti-ulcer
      drug, sucralfate, was studied on ischaemia and reperfusion (e.g. induced gastric
      lesions, intraluminal bleeding, changes in vascular permeability and non-protein
      sulfhydryl levels in the rat stomach). Allopurinol was used as a known standard
      antioxidant drug. Rats were subjected to 30 min of gastric ischaemia in the
      presence of 100 mmol/L hydrochloric acid and reperfusion periods of 15, 30 or 60
      min duration. The gastric lesions were assessed microscopically under an inverted
      microscope. The vascular permeability was quantified by measuring the
      extravasated Evans blue in the stomach. There were significantly greater numbers
      of gastric lesions, intraluminal bleeding and leakage of Evans blue during all
      reperfusion periods as compared with those of ischaemia, with maximum effects
      occurring at 60 min following reperfusion. Pretreatment with sucralfate (31.25
      250 mg/kg, p.o.) or allopurinol (12.5-50 mg/kg, i.p.) 30 min before the
      procedure, dose-dependently reduced the gastric lesions, intraluminal bleeding,
      and decreased the vascular permeability induced by ischaemia and reperfusion.
      Furthermore, sucralfate dose-dependently reverses the ischaemia and reperfusion
      induced depletion of mucosal non-protein sulfhydryl levels and inhibited the
      superoxide radical production in both cell-free xanthine-xanthine oxidase and in
      the stimulated polymorphonuclear cellular systems. These results suggest that the
      protection produced by sucralfate against gastric injury may be due to its
      antioxidant effects.

PMID- 9257238
TI  - Circulating antioxidants in ulcerative colitis and their relationship to disease
      severity and activity.
AB  - Oxygen free radicals produced by neutrophils are important in the pathogenesis of
      mucosal damage in ulcerative colitis. Vitamin A, vitamin E and cysteine in the
      plasma can scavenge free radicals. In the present study, plasma levels of vitamin
      A, vitamin E, cysteine, cystine and protein-bound cysteine were measured in
      active ulcerative colitis before and immediately after treatment of the active
      disease, and correlated with disease severity, extent and activity. Plasma
      vitamin A and cysteine were significantly reduced in active ulcerative colitis
      compared with controls. Levels of vitamin E, cystine and protein-bound cysteine
      were not significantly altered in active ulcerative colitis. Vitamin A and
      cysteine concentrations returned to normal levels (P < 0.05) within 2 weeks of
      treating active colitis. There were significant negative correlations between
      clinical severity and the plasma concentrations of vitamin A and cysteine. Plasma
      cysteine levels also correlated inversely to disease extent. Depletion of the
      circulating antioxidants, vitamin A and cysteine, in active ulcerative colitis is
      likely to be important in the pathophysiology of the disease.

PMID- 9257239
TI  - Case report: haemorrhagic colitis associated with royal jelly intake.
AB  - The case report of a 53-year-old woman with abdominal pain and bloody diarrhoea
      is described. Prior to the onset of symptoms the patient had taken royal jelly
      for 25 days. Colonoscopy revealed that the mucosa was haemorrhagic and oedematous
      throughout the 20 cm long sigmoid colon. Histopathologically, mucosal
      haemorrhage, oedema, and infiltration of inflammatory cells were observed.
      Transmission electron microscopic examination revealed platelet aggregation in
      30% of capillaries in the mucosal lesions. The drug-induced lymphocyte
      stimulation test was slightly positive for royal jelly (847 c.p.m., SI = 147%)
      compared with the control (576 c.p.m.). The patient's signs and symptoms
      disappeared within a few days after the initiation of conservative therapy, and
      the colonic lesions disappeared after 2 weeks of this therapy. This is the first
      reported case of haemorrhagic colitis associated with royal jelly intake.

PMID- 9257240
TI  - Quantitative measurement of HCV RNA in the serum: a comparison of three assays
      based on different principles.
AB  - Quantitative measurement of hepatitis C virus (HCV) RNA is useful in patients
      with chronic hepatitis C, especially with interferon treatment. We examined the
      clinical usefulness of the AMPLICOR monitor assay, a newly developed assay for
      quantitative measurement, by comparing it with two other assays with different
      principles. A total of 48 patients with chronic hepatitis C who were treated with
      interferon-alpha (IFN-alpha) were studied: 19 were complete responders and 29
      were non-responders. Hepatitis C virus RNA was measured quantitatively by
      AMPLICOR, branched DNA (bDNA) probe, and competitive polymerase chain reaction (C
      PCR) assays. An internal quantification standard was used in the AMPLICOR assay.
      A cDNA competitor with a deletion of 15 base pairs in the middle portion was used
      in the C-PCR method. The concentration of HCV RNA was significantly correlated
      between the three assays adopted in this study. Sensitivity of assays was 100% by
      C-PCR, 90% by AMPLICOR and 69% by bDNA assays. The active quantitative range was
      best with the C-PCR assay and worst with the bDNA assay. The bDNA assay had a
      tendency to exhibit lower values for patients with serotype 2 than did the other
      two assays. The predictive rate of the long-term response to IFN-alpha therapy,
      before its initiation, was over 75% in all three assays. The predictive rate just
      after completing IFN-alpha therapy was as high as 80% by C-PCR and the AMPLICOR
      assays, but was low (58%) with the bDNA assay. The handling of the bDNA and
      AMPLICOR assays was much easier than the C-PCR assay, which required time and
      skill. These results indicate that the AMPLICOR assay is a simple and reliable
      method for measuring the serum concentrations of HCV RNA, and thus is suitable
      for clinical application.

PMID- 9257241
TI  - B7-2 positive cells around interlobular bile ducts in primary biliary cirrhosis
      and chronic hepatitis C.
AB  - Bile duct damage in patients with chronic hepatitis C (hepatitis-associated bile
      duct lesion) as well as that in patients with primary biliary cirrhosis (PBC;
      chronic non-suppurative destructive cholangitis), may be causally related to
      immunological assaults. Efficient antigen presentation is known to require the
      provision of a costimulatory signal which is dependent on the CD28 on T cell
      surfaces, and that at least two molecules, B7-1 and B7-2, work as costimulatory
      ligands for CD28. In this study, we examined immunohistochemically, the
      expression of B7-2 in portal tracts of liver biopsy specimens obtained from 75
      patients with chronic hepatitis C who had hepatitis-associated bile duct lesions,
      and from 63 PBC patients with chronic non-suppurative destructive cholangitis. B7
      2 positive cells were recognizable as large mononuclear cells scattered in portal
      tracts. Some of these cells showed a dendritic cell-like appearance. B7-2
      positive cells were observed more frequently (41%) in PBC liver specimens than in
      chronic hepatitis C specimens (17%, P < 0.05). In PBC livers, such cells were
      preferentially observed around the damaged bile duct with a few located in the
      biliary epithelial layer. There was no such finding in chronic hepatitis C
      livers. The frequency and density of B7-2 positive cells in the liver specimens
      tended to decrease according to the stage of PBC (45% in stages 1 and 2, and 33%
      in stages 3 and 4; P = 0.10), whereas with chronic hepatitis C, no such tendency
      was observed. These findings suggest that B7-2 positive cells may play a role in
      the bile duct lesions that appear in the early histological stages of PBC and
      that the immunological mechanisms of bile duct damage, particularly of antigen
      presentation and B7-2 expression, differ between PBC and chronic hepatitis C.

PMID- 9257242
TI  - Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C.
AB  - Cryoglobulinaemia is the most common immunological disorders seen in patients
      with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and
      clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic
      hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this
      phenomenon were also evaluated. Fifty-four (44%) of the 122 patients with chronic
      hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with
      cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia,
      neuropathy and renal involvement. The patients with cryoglobulinaemia were
      predominantly female and had a significantly higher mean serum level of
      rheumatoid factor and a lower mean serum C4 level compared with patients without
      cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P <
      0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto
      antibodies, and the rate of cirrhosis were not significantly different between
      the two groups. Univariate logistic regression analysis showed female serum
      levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL),
      C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of
      cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis
      showed only serum C4 levels (< 20 mg/dL) as a significantly independent
      predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had
      cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis
      C patients with cryoglobulinaemia and the serum C4 level was the only clinical
      independent predictor associated with this phenomenon. Hepatitis C virus genotype
      and serum viral load were not clinical independent predictors.

PMID- 9257243
TI  - Hepatitis C virus RNA present in saliva but absent in breast-milk of the
      hepatitis C carrier mother.
AB  - In order to examine whether saliva and breast-milk are mediators of the vertical
      transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum,
      saliva, and breast-milk samples from 11 HCV carrier mothers were collected at the
      time of delivery, and at approximately 1- to 3-months intervals for as long as 30
      months postpartum. Serum was also sampled from their children. All samples were
      analysed for the presence of HCV RNA, using the nested polymerase chain reaction
      method. No HCV RNA was detected in any breast-milk samples. In saliva, HCV RNA
      was detected in four of the 11 mothers (36%). These four mothers also had liver
      function abnormalities. Hepatitis C virus RNA was not detected in any serum
      samples of the children, and all children had normal liver function. The children
      were monitored for periods from 2 to 44 months. During this period, there was no
      evidence of virus transmission. Breast-milk is not likely to be a source of
      mother-to-child transmission of HCV. Maternal saliva may harbour HCV, but it may
      not result in infant infection.

PMID- 9257244
TI  - Review: molecular epidemiology of hepatitis C virus.
AB  - Molecular techniques have been used to investigate the epidemiology of hepatitis
      C virus (HCV) at several different levels. At a global level, the time of
      divergence of the diverse HCV genotypes isolated from different geographical
      regions has been estimated from the rate of divergence observed among a cohort of
      individuals infected from a common source. Estimates of more than 300 years for
      virus subtypes and more than 500-2000 years for virus types are consistent with
      their current geographical distributions. Analysis of virus sequences has also
      provided evidence for a common source of infection in several large-scale
      outbreaks of HCV infection, although where there is evidence that the implicated
      source contains more than one variant it may be difficult to distinguish
      individuals infected by different sources. Finally, sequence analysis has been
      used to investigate the vertical or horizontal transmission of HCV between pairs
      of individuals. The hypervariable region of the E2 gene is the most informative
      region to study if samples are available soon after the transmission event, but
      evidence for more distant events can still be obtained from analysis of genes
      such as NS5b and E1. Interpretation of some studies is complicated by the
      conservation of the gene region studied, or by the failure to make comparisons
      with sequences from epidemiologically unrelated viruses.

PMID- 9257246
TI  - More transporters for organic anions in the hepatocyte canalicular membrane or
      merely a reflection of an overlapping spectrum of substrate specificities for
      known transporters?

PMID- 9257245
TI  - Effect of taurolithocholate-3-sulphate on biliary excretion of
      sulphobromophthalein and dibromosulphophthalein in the Eisai hyperbilirubinaemic
      rat.
AB  - We previously reported that biliary lithocholate-3-sulphate excretion was
      inhibited by dibromosulphophthalein, not by sulphobromophthalein in Eisai
      hyperbilirubinaemic rats (EHBR); instead its excretion was inhibited by both
      organic anions in control rats. In the present study, the effect of
      taurolithocholate-3-sulphate on the excretion of sulphobromophthalein and
      dibromosulphophthalein was studied in EHBR and control Sprague-Dawley rats.
      Taurolithocholate-3-sulfate infusion inhibited biliary excretion of
      sulphobromophthalein and dibromosulphophthalein in both EHBR and control rats.
      These findings indicate that in control rats biliary excretion of
      taurolithocholate-3-sulphate is mediated by a carrier common for both organic
      anions, and that in EHBR, in which the canalicular multispecific organic anion
      transporter is impaired, the excretory pathway for taurolithocholate-3-sulphate
      is also partly identical to that for both organic anions.

PMID- 9257247
TI  - Transcytotic vesicle fusion with canalicular membranes is modulated by
      phospholipid species: implications for biliary lipid secretion.
AB  - Phospholipid species modulate bile metastability and the subselection of such
      species for biliary secretion occurs at the canalicular membrane. In this study,
      the role of phospholipid head groups and hydrophobic indices in transcytotic
      vesicle fusion with the canalicular membrane inner leaflet was investigated using
      rat canalicular membrane vesicles (CMV) and liposomes. The CMV were purified from
      Sprague-Dawley rat liver, and small unilamellar vesicles (SUV) of
      phosphatidylserine (PS), phosphatidylcholine (PC) and mixtures of PS/PC (1:1, 2:1
      and 4:1) were labelled with 8 mol% of octadecyl rhodamine B chloride (R18). The
      PC species used in this study were egg yolk PC (EYPC), soybean PC (SBPC),
      dipalmitoyl PC (DPPC) and dilinoleoyl PC (DLPC). Fusion of SUV with CMV was
      initiated by the addition of a millimolar concentration of Ca2+ and the degree of
      fusion was estimated by the increase of R18 fluorescence. Ca(2+)-dependent fusion
      of SUV consisting of PS, and PS/PC (4:1) with CMV was observed (PS > PS/PC; 4:1),
      whereas no detectable fusion was evident between CMV and SUV of PC alone or PS/PC
      (1:1 or 2:1). The rank order of fusibility between CMV and SUV of PS/PC (4:1)
      containing various PC species was PS/DLPC > PS/SBPC > PS/EYPC > PS/DPPC. The
      hydrophobic index of PC as determined by high performance liquid chromatography
      (HPLC) was related closely to liposome fusibility (r = -0.88). These results
      suggest that transcytotic vesicle fusion with the canalicular membrane inner
      leaflet is regulated by the phospholipid hydrophobicity of the vesicles.

PMID- 9257248
TI  - Liver involvement in epidemic haemorrhagic fever: in situ hybridization,
      immunohistochemical and pathological studies.
AB  - In the present study, liver biopsy specimens from 37 patients with epidemic
      haemorrhagic fever (EHF) were investigated by using light and electron
      microscopy, immunohistochemistry for the EHF virus envelope protein G2 and in
      situ hybridization (ISH) for EHF viral RNA. Immunostaining and in situ
      hybridization were both positive, and a few of the aetiological agents, the EHF
      virus (EHFV) particles, were found individually within the dilated Golgi
      cisternae and vesicles, and the dilated rough endoplasmic reticulum of the
      hepatocyte. The pathological alterations of the liver cells infected with EHFV
      were: hepatocellular degeneration, cytoplasmic vacuolation, and spotty necrosis;
      moreover, zonal necrosis was present and adjacent to the narrowed and occluded
      sinusoids. In degenerated and spotty necrotic cells, the positive signals from of
      ISH for EHFV RNA and those from immunostaining for the virus protein were both
      stronger than those in the zonal liver cell necrosis area. The results showed
      that hepatocellular degeneration and spotty necrosis might be directly related to
      the virus and its duplication inside the liver cells, while the zonal necrosis
      was ischaemic and thought to be caused by microcirculation dysfunction.

PMID- 9257249
TI  - Different viral aetiology of hepatocellular carcinoma between two hepatitis B and
      C endemic townships in Taiwan.
AB  - In Taiwan, we found two hepatitis B virus (HBV)- and hepatitis C virus (HCV)
      endemic townships, Paisha and Tzukuan, with an anti-HCV prevalence of 19 and 37%
      in men, and 26 and 38% in women, respectively. The hepatitis B surface antigen
      (HBsAg)-positive rates were 25 and 18%, for men and women in Paisha, and 25 and
      22% in Tzukuan, respectively. According to the national death certification
      database (1982 to 1991), the annual age-adjusted mortality rates per 100,000
      population for liver cancer among men and women were 83.0 and 13.8, respectively,
      in Paisha, and 55.9 and 17.0 in Tzukuan compared with 30.9 and 9.1 in Taiwan as a
      whole. The male-to-female ratios were 6.0 in Paisha and 3.3 in Tzukuan. Aetiology
      of 11 cases of hepatocellular carcinoma (HCC) from Paisha and 14 cases from
      Tzukuan were analysed. All HCC cases from Paisha were HBsAg positive, while 13/14
      HCC cases from Tzukuan were anti-HCV positive. The endemic duration of HCV in
      Tzukuan seemed long enough to induce HCC, but the HCV appeared to be a newly
      introduced infection in Paisha.

PMID- 9257250
TI  - Case report: interferon induced coma in Sheehan's syndrome.
AB  - A 54-year-old woman who was being treated with 10 million units (mu) of natural
      interferon (IFN)-alpha per day for chronic active hepatitis C at a local clinic,
      developed coma on the fourth day of treatment. On admission to Yamagata
      University Hospital, she was still in a state of semicoma with severe
      hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration
      of electrolytes, her condition improved remarkably. Endocrinological loading
      tests showed a hypofunction of the anterior pituitary gland. In consideration of
      these results, and her past experiences of haemorrhage during childbirth and
      subsequent amenorrhoea, we diagnosed her illness as a coma as a result of
      Sheehan's syndrome which had become overt during IFN therapy. She recovered
      completely after treatment with hydrocortisone and l-thyroxine.

PMID- 9257251
TI  - Visual and auditory evoked responses in acute severe hepatitis.
AB  - Evoked responses have not been studied in patients with acute severe hepatitis
      (ASH) with or without hepatic encephalopathy. This prospective study was
      undertaken to find out diagnostic as well as prognostic value of visual evoked
      responses (VER), and brain stem auditory evoked responses (BAER) in patients with
      ASH with or without encephalopathy. Visual evoked responses and BAER were studied
      in 20 patients (14 males and six females) with ASH. The patients were diagnosed
      as having severe hepatitis if acute hepatitis was associated with raised serum
      bilirubin and serum transaminases, and if they had a prothrombin time index of <
      50%. After a detailed neuropsychiatric examination of each patient, the study
      sample was divided into two groups of 10 patients: ASH without encephalopathy
      (ASH-WOE), and ASH with encephalopathy (fulminant hepatic failure, FHF). The
      median P100 latencies of FHF patients were significantly increased compared with
      controls and patients in the ASH-WOE group. Abnormal P100 latencies, exceeding
      95th percentile values of the controls, were present in one patient in the ASH
      WOE group and six patients in the FHF group. The median interpeak latencies I
      III, III-V and I-V were significantly prolonged in the FHF group. Interpeak
      latencies III-V were also increased significantly in patients in the ASH-WOE
      group. While abnormal BAER were seen frequently in both groups, VER abnormalities
      were largely confined to patients in the FHF group. In the FHF group, six out of
      10 patients survived and exhibited clinical improvement in the status of hepatic
      encephalopathy. Evoked responses were repeated after 2-3 weeks of recovery in
      these patients and VER abnormalities showed a tendency to normalize, thereby
      suggesting a prognostic implication. The incidence of abnormal VER in hepatic
      encephalopathy complicating ASH far exceeded that of abnormal BAER. Markedly
      prolonged P100 latencies in FHF patients indicate poor prognosis.

PMID- 9257252
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      fourteenth official report--1997.

PMID- 9257253
TI  - Predicting outcome after listing for heart transplantation in children:
      comparison of Kaplan-Meier and parametric competing risk analysis. Pediatric
      Heart Transplant Study Group.
AB  - After listing for pediatric heart transplantation, at any point in time one of
      the following possibilities could have occurred; death, transplantation, removal
      from the list because of clinical improvement, or continuing to wait. In the
      setting of those competing outcomes, the Kaplan-Meier estimate portrays the time
      relatedness of an event while ignoring the effect of the other possible outcomes.
      The competing outcomes method, however, depicts the time relatedness of an event
      while solving for all possible events simultaneously. The competing outcomes
      method may potentially provide more accurate information regarding the actual
      proportion of patients experience an outcome after listing.

PMID- 9257254
TI  - Adult heart transplantation under tacrolimus (FK506) immunosuppression:
      histopathologic observations and comparison to a cyclosporine-based regimen with
      lympholytic (ATG) induction.
AB  - BACKGROUND: Tacrolimus (FK506) is an effective immunosuppressant for human heart
      transplantation, but information about its effects on cardiac allograft and
      nonallograft kidney and liver histopathologic study is limited. METHODS: We
      therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results
      from 80 heart transplant recipients who received tacrolimus as baseline
      immunosuppression. These were compared with 619 endomyocardial biopsy specimens
      and four autopsy results from 51 patients treated with cyclosporine-based
      immunosuppression with lympholytic induction (CLI) by use of rabbit anti
      thymocyte globulin. Twenty-one histologic features including the International
      Society for Heart and Lung Transplantation histopathologic grade were
      retrospectively assessed without knowledge of the treatment regimen. The
      lymphocyte growth index on biopsy specimens obtained from these patients was also
      compared. RESULTS: In general, there were no qualitative differences in the
      histopathologic appearance of various allograft syndromes between tacrolimus- and
      CLI-treated patients. Thus histopathologic criteria used to diagnose various
      graft syndromes are applicable under tacrolimus immunosuppression. However, early
      (between 10 and 30 days) after transplantation, biopsy specimens from patients
      treated with tacrolimus showed a significantly higher percentage of inflamed
      fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and
      the rejection grade tended to be slightly higher (p = 0.08). In contrast, during
      the late transplantation period (275 to 548 days), biopsy specimens from patients
      treated with CLI showed a significantly higher percentage of inflamed fragments
      (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p =
      0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall
      freedom from any grade 3A or higher rejection was greater in the CLI-treated arm,
      tacrolimus was successfully used to treat refractory rejection in three patients
      from the CLI-treated arm. Concern has been raised in the literature about the
      possibility of tacrolimus being a direct hepatotoxin and an accelerant of
      allograft obliterative arteriopathy. However, no evidence to support either of
      these contentions was detected in this patient population. In contrast,
      tacrolimus is clearly nephrotoxic, although similar to cyclosporine in this
      regard. CONCLUSIONS: Tacrolimus is an effective immunosuppressive drug for heart
      transplantation. The cardiac allograft histopathologic study of patients treated
      with tacrolimus immunosuppression does not significantly differ from those given
      conventional, cyclosporine-based triple therapy with lympholytic induction.

PMID- 9257255
TI  - The alternate recipient list for heart transplantation: does it work?
AB  - BACKGROUND: One quarter of patients awaiting heart transplantation die while on
      the waiting list. This is largely due to the shortage of donor organs. The
      alternate recipient list was created to establish a means by which patients who
      would otherwise be turned down for heart transplantation solely because of age
      over 65 or a need for a third heart transplantation can receive organs considered
      marginal that may otherwise be wasted. The hope is that these patients may
      achieve improved survival with these substandard hearts than they would achieve
      with medical therapy alone. METHODS: Twenty-two patients ages 47 to 71 years
      (mean 66.7 years) were listed on the alternate recipient list at the University
      of California at Los Angeles Medical Center from 1991 to 1996. Seventeen patients
      underwent heart transplantation from the alternate waiting list. The outcome of
      this group was compared with the outcome of a contemporaneous group of 266
      patients ages 18 to 66 years (mean age 52.1 years) from the standard heart
      transplantation waiting list. RESULTS: The early mortality rate for the patients
      in the alternate group was 11.8% (2/ 17). Actuarial survival from time of
      orthotopic heart transplantation at 6 months and 1 year was the same 74.5% at a
      mean follow-up was 13.4 months. In comparison, the early mortality rate for the
      patients on the standard list was 5.6% (15/266), and actuarial survival at 6
      months and 1 year was 86.8% and 83.1%, respectively (mean follow-up was 30
      months). There was no significant difference in early mortality rate or actuarial
      survival between the two groups. CONCLUSION: The alternate recipient list for
      heart transplantation is a valid and ethical option for patients who would
      otherwise be denied heart transplantation. It provides these patients with
      similar early and medium-term outcomes in comparison to patients on the standard
      list, and organs that may otherwise be wasted are used.

PMID- 9257256
TI  - The prognostic impact of immunosuppression and cellular rejection on cardiac
      allograft vasculopathy: time for a reappraisal.
AB  - BACKGROUND: Our current immunosuppressive strategies have made little impact on
      the development of cardiac allograft vasculopathy, the leading cause of long-term
      allograft loss. This study sought to evaluate the relationship of cellular
      rejection and immunosuppressive therapy with the development of morbid events
      resulting from cardiac allograft vasculopathy. METHODS: The study population
      consisted of 163 consecutive patients who received heart transplants between
      January 1990 and May 1994. Data regarding nonimmunologic risk factors (lipids,
      obesity indexes, hypertension, donor age and sex, cytomegalovirus infection,
      diabetes mellitus, time after transplantation, and cold ischemic time),
      immunologic factors (histocompatibility, episodes of treated rejection, and
      average first-year biopsy rejection score), and immunosuppressive regimens
      (cumulative prednisone dose, average daily prednisone dose, mean cyclosporine
      level, average cyclosporine daily dose, cumulative azathioprine dose, and average
      daily azathioprine dose) were collected and analyzed in all patients. The
      diagnosis of cardiac allograft vasculopathy was established in all patients by a
      combination of necropsy, angiography, and intravascular ultrasound examination of
      the allograft vasculature. Cardiac events were defined as sudden death,
      myocardial infarction, and need for revascularization. RESULTS: Of all variables
      assembled, stepwise logistic regression recognized cumulative prednisone dose >
      15 gm (relative risk [RR] 5.7; p = 0.01), donor age > 35 years (RR 3.73; p <
      0.05), and average biopsy rejection score > 1 (RR 2.77; p < 0.05) as independent
      adverse predictors of cardiac events. In distinction, average daily cyclosporine
      dose > 4.5 mg/kg/day was found to confer a protective effect (RR 0.16; p = 0.03).
      CONCLUSIONS: The development of cardiac events as a result of cardiac allograft
      vasculopathy is influenced by the interdependence of allograft rejection and the
      balance of immunosuppression. The clinical implications of these findings point
      to the need for a reappraisal of our traditional approach to using
      corticosteroids (acute and maintenance) and cyclosporine (maintenance) in heart
      transplantation.

PMID- 9257257
TI  - Volume reduction surgery in the native lung after single lung transplantation for
      emphysema.
AB  - The natural history of emphysema suggests that progression of disease in the
      native lung may contribute to late deterioration in respiratory function after
      single lung transplantation. In this report, we describe our experience with
      unilateral volume reduction surgery in three single lung transplant recipients
      with emphysema. Each patient had had a late decline in lung function with a
      recurrence of symptoms. Chest radiographs demonstrated hyperinflation of the
      native lungs with encroachment on the grafts. Serial pulmonary function testing
      documented progressive reduction in expiratory flows with increases in residual
      volumes. Exercise testing confirmed severe intolerance to maximal exercise.
      Unilateral volume reduction surgery was undertaken at 36, 39, and 55 months after
      transplantation without incident. Radiographs obtained after the procedures
      demonstrated restoration of normal diaphragmatic contour, decreased aeration of
      the native lungs, and improved inflation of the allografts. Exercise testing at 3
      months documented a mean improvement in maximal oxygen consumption of 35%.
      Expiratory flows improved by a mean of 60%. Quantitative ventilation and
      perfusion scans, however, were essentially unchanged. This experience suggests
      that unilateral volume reduction surgery may be considered as an alternative
      strategy in single lung transplant recipients with emphysema who exhibit
      clinically significant functional deterioration. Differentiation of the adverse
      effects of hyperinflation of the native lung from other potential causes of late
      deterioration might not be necessary but may be predictive of the degree of
      functional improvement after volume reduction. The relief of thoracic
      overdistention seems to play a primary role in the improvement pulmonary
      function.

PMID- 9257258
TI  - Transgenic human decay accelerating factor makes normal pigs function as a
      concordant species.
AB  - BACKGROUND: Increasing interest has focused on xenotransplantation as a potential
      solution to the organ shortage. To overcome hyperacute rejection, pigs have been
      produced that are transgenic for human decay accelerating factor (DAF). For the
      evaluation of the effects of human DAF, an ex vivo working heart model was used.
      METHODS: We compared hemodynamic performance of four transgenic pig hearts (group
      A) with that of four Landrace pig hearts (group B) and eight rhesus monkey hearts
      (group C). For perfusion fresh blood had been taken from healthy volunteers. From
      the coronary sinus effluent, samples were taken for the determination of 6-keto
      prostaglandin F1 alpha, prostaglandin E2, creatine phosphokinase, and lactate
      dehydrogenase, respectively. Hemodynamic parameters were measured continuously
      for 150 minutes after the start. After 15 minutes of reperfusion, the Langendorff
      mode was switched to the working heart model. After hearts failed to pump against
      the afterload column, experiments were terminated, and tissue sections were taken
      for electron microscopy. RESULTS: Groups A and C showed superior cardiac
      performance as measured by stroke work index (SWI) that exceeded group B by 2.5
      to 3 times (p < 0.05). In all three groups the SWI slowly decreased during
      perfusion. In group B, SWI decreased to a minimum as early as 90 minutes after
      the start. In all groups, 6-keto prostaglandin F1 alpha and prostaglandin E2 as
      indicators of endothelial cell activation increased. In group B, however, the
      levels exceeded those of groups A and C by six and nine times, respectively (p <
      0.05). As markers of myocardial damage, creatine phosphokinase and lactate
      dehydrogenase increased in all groups. But again levels in group B exceeded those
      of groups A and C by four to five times (p < 0.05). Electron microscopy revealed
      single cell necrosis in group B, whereas groups A and C showed interstitial edema
      only. CONCLUSIONS: Our experiments indicate a crucial role of DAF in preventing
      rejection in discordant species combinations. Transgenic human DAF seems to
      inhibit successfully complement-mediated damage to the endothelial cell, thus
      preventing endothelial activation and consequently myocardial damage. Transgenic
      human DAF makes a discordant species (pig) function as a concordant species, that
      is, hyperacute rejection does not occur.

PMID- 9257259
TI  - Altered myocardial phenotype after mechanical support in human beings with
      advanced cardiomyopathy.
AB  - BACKGROUND: Left ventricular assist devices (LVAD) provide lifesaving circulatory
      support to patients awaiting heart transplantation. To date, the extent to which
      sustained mechanical unloading alters the phenotype of pathologic myocardial
      hypertrophy in dilated cardiomyopathy is unknown. METHODS: We examined left
      ventricular size, myocyte and myocardial immunoreactivity for atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP) in eight patients with advanced
      dilated cardiomyopathy before and after LVAD support. The mean duration of
      congestive heart failure was 18 +/- 5 months, and LVAD support averaged 42 +/- 4
      days before heart transplantation. RESULTS: Echocardiographically determined left
      ventricular mass decreased from 505 +/- 83 to 297 +/- 52 gm (p < 0.05) during
      LVAD support, whereas minimum myocyte diameter decreased from 28.1 +/- 0.9 to
      21.7 +/- 0.6 microns (p < 0.01) in transmural myocardial tissue specimens.
      Overall left ventricular ANP immunopositivity decreased from 48% at LVAD
      placement to 12% at transplantation (p < 0.05), whereas BNP immunopositivity
      decreased from 28% to 4% after LVAD support. Moreover, a gradient of ANP and BNP
      immunostaining from subendocardium to epicardium observed before mechanical
      unloading diminished after LVAD support. Analysis of the relationship between
      left ventricular mass and ANP immunopositivity revealed a close and highly
      significant correlation between these variables. CONCLUSIONS: These studies
      demonstrate remarkable left ventricular plasticity even in the presence of
      advanced cardiomyopathy. Parallel reductions in myocardial mass and myocyte size
      with reductions in ventricular ANP and BNP immunostaining indicate a novel
      regression of the phenotype of pathologic hypertrophy within the human myocardium
      after LVAD support.

PMID- 9257261
TI  - Development of a specific fluoroimmunoassay for ovine albumin.
AB  - A fluoroimmunoassay has been developed to measure serum levels of albumin in
      sheep. It employs ovine albumin labelled with fluorescein as the tracer and a
      rabbit antiserum raised against ovine albumin. Separation of the antibody bound
      and free fractions is achieved using a second antiserum directed against the Fc
      of rabbit immunoglobulin G and, to simplify the assay, the two antisera are
      premixed prior to use. Assay validation parameters are satisfactory and the
      reagents are predicted to be stable for at least one year at 4 degrees C. In
      contrast to the bromocresol green method, the assay is unaffected by
      immunoglobulins. A reference range for serum albumin levels has been established
      in lambs, normal ewes and ewes undergoing immunisation. Mean serum levels were
      38.8, 51.3 and 37.8 g/l respectively. The sensitivity of the assay also enabled
      its use to monitor albumin levels at various stages during the production of
      specific antibody fragments from ovine antisera for therapeutic purposes.

PMID- 9257262
TI  - Bispecific rabbit Fab'-bovine serum albumin conjugate used in hemagglutination
      immunoassay for beta-microseminoprotein.
AB  - A polyclonal bispecific (bifunctional) antibody was prepared to develop a
      hemagglutination immunoassay for beta-microseminoprotein (beta-MSP), a
      predominant seminal protein. Three types of F(ab')2 fragments of rabbit IgG,
      affinity-purified anti-human red blood cell (RBC) F(ab')2 nonaffinity-purified
      anti-beta-MSP F(ab')2 and nonspecific (nonimmunized) F(ab')2, were mixed to
      obtain a F(ab')2 mixture containing 10% anti-RBC molecules and 10% anti-beta-MSP
      molecules. Fab' was obtained from the F(ab')2 mixture, and then reacted with
      maleimide-activated bovine serum albumin (BSA) at a molar ratio of 10:1. As
      estimated by the decrease in the maleimide content, approximately 7 Fab'
      molecules were introduced per one BSA molecule. The bispecific (anti-beta-MSP and
      anti-RBC) Fab'-BSA conjugate thus prepared was incubated successively with a
      human RBC suspension and with samples. In the presence of beta-MSP, RBCs become
      agglutinated, providing a test simple for forensic semen identification.

PMID- 9257260
TI  - Value of right ventricular ejection fraction in predicting short-term prognosis
      of patients with severe chronic heart failure.
AB  - BACKGROUND: The prognosis of chronic heart failure has been studied extensively,
      but factors predicting short-term outcome in patients with severe chronic heart
      failure are still poorly defined, and the current indications for heart
      transplantation as a treatment for end-stage heart failure need on objective
      analysis. METHODS: Purpose of the study was to identify the determinants of short
      term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8
      +/- 11 years). Referred for heart transplantation because of severe chronic heart
      failure, the patients were admitted with left ventricular ejection fraction
      markedly depressed and had had symptoms in spite of an optimal standardized
      medical therapy for at least 1 month. Baseline clinical and instrumental
      evaluation included right-sided heart catheterization with a flow-directed
      multilumen thermodilution catheter, which enables determination of pressures,
      cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most
      patients were in New York Heart Association class III (61%) and IV (24%), and the
      hemodynamic profile was characterized by mean left ventricular ejection fraction
      of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary
      wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg,
      right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up
      of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died
      (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left
      ventricular ejection fraction between patients divided on the basis of outcome,
      whereas right ventricular ejection fraction was significantly lower in patients
      who died or underwent transplantation. Cox multivariate analysis showed three
      independent prognostic variables: cause (p = 0.03), heart failure score (p =
      0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival
      (10 months) was significantly (p = 0.000) different in patients with > or = 24%
      or < 24% right ventricular ejection fraction. Statistical analysis identified
      right ventricular ejection fraction as the single variable to be highly
      correlated with an increased risk of early death. CONCLUSIONS: This study
      suggests that right ventricular function is a crucial determinant of short-term
      prognosis in severe chronic heart failure. Statistical analysis identified right
      ventricular ejection fraction, determined by thermodilution during right-sided
      heart catheterization, as the single most important predictor of short-term
      prognosis in a large cohort of patients who had symptoms in spite of a
      standardized, optimized, multipharmacologic treatment. The variable allows a
      useful risk stratification in patients with severe chronic heart failure and
      uniformly depressed left ventricular ejection fraction and provides guidance in
      the assessment of indications and timing for transplantation.

PMID- 9257263
TI  - Water immiscible solvent based immunoassay.
AB  - A competitive monoclonal antibody-based immunoassay which quantifies a
      hydrophobic hapten (Rx) in water immiscible solvents, obviating the need of a pre
      extraction step, has been developed. Approximately linear dose response profiles
      of analyte, over the range 1-20 ugml-1 in the hydrophobic solvents, hexane,
      toluene and xylene were obtained. UV spectrophotometric analyses of Rx dosed
      hexane confirm the phenomenon of antibody-mediated transfer of analyte from the
      organic to the aqueous milieu. Preliminary data on the effect of water immiscible
      solvents on the immunoreactivity of a monoclonal antibody in free solution are
      presented. The potential industrial applications of water immiscible solvent
      based immunoassays are discussed.

PMID- 9257264
TI  - Sensitive human thyrotropin immunoradiometric assay set up by the identification
      and minimization of nonspecific bindings.
AB  - An immunoradiometric assay (IRMA) of human thyrotropin (hTSH), based on magnetic
      solid phase separation, was studied especially in terms of its nonspecific
      bindings (B0) which were identified as a product of the interaction between an
      altered form of radioiodinated anti-hTSH monoclonal antibody (125I-mAB) and the
      uncoupled magnetizable cellulose particle (matrix). Preincubation with the same
      matrix, solid phase saturation with milk proteins, tracer storage at 4 degrees C
      and serum addition during incubation were found to be particularly effective in
      preventing their formation. These findings were used to reproducibly decrease
      nonspecific bindings to values < 0.1% (or < 70 cpm), thus increasing the signal
      to-noise ratio (B60/B0) up to values of 300-500. This way hTSH radioassays were
      obtained with functional sensitivities of about 0.05 mIU/L and analytical
      sensitivities of the order of 0.02 mIU/L. Such sensitivities, and, more
      importantly, a general improvement in assay performance, were obtained in a
      highly reproducible manner and all over the useful tracer life.

PMID- 9257265
TI  - Quantification of cell-associated and free antigens in Bordetella pertussis
      suspensions by antigen binding ELISA.
AB  - In order to achieve batch-to-batch consistency of whole-cell pertussis vaccines,
      properties relevant for protection and safety should be characterised. Therefore,
      ELISAs to quantify pertussis toxin (PT), filamentous haemagglutinin (FHA), 92 kD
      outer membrane protein (92 kD-OMP) and pertactin (PRN) in Bordetella pertussis
      (B. pertussis) suspensions were developed. In this paper the influence of the
      bacterial growth stage on antigen production and antigen release into the
      supernatant was studied for pertussis strains 134, 509 and CS. The levels of cell
      associated and free antigens during growth were strongly strain and antigen
      dependent. Because of this, the proportion of cell-associated antigens changed
      during cultivation for all three strains. Substantial amounts of PT and PRN were
      released into the supernatant, while little free FHA and 92 kD-OMP were found.
      The amount of cell-associated FHA declined rapidly during growth, whereas cell
      associated 92 kD-OMP contents increased. These findings demonstrate that,
      although antigen exposure and release differ from strain to strain, the main
      factor that determines the antigen production and release is the growth phase.

PMID- 9257276
TI  - [Hyperparathyroidism from giant parathyroid cyst].

PMID- 9257277
TI  - [Is the repetition of a sleep study with portable system without surveillance
      useful?].

PMID- 9257278
TI  - Effect of hydration on the structure, dynamics and function of photosynthetic
      membranes of purple bacteria.
AB  - NMR spectra and relaxation times T1 and T2 for 31P in membranes of Rhodobacter
      sphaeroides were investigated at different relative humidity levels. The results
      are compared to the hydration curves, fatty acid composition and the structure
      dynamic and functional characteristics of the membranes of photosynthetic
      bacteria Rb. sphaeroides, Rhodospirillum rubrum and Ectothiorhodospira
      shaposhnikovii. The differences in the state of lipid phase of these membranes
      are revealed under low humidity, and this is conducive to variability of their
      structural dynamic and functional characteristics during the hydration process.
      Based on the results obtained and the data on model systems, four stages of
      hydration process are distinguished with different effects on the structure and
      dynamics of membrane components. These stages are: hydration of a portion of
      polar groups, involvement of water molecules in the hydrogen bonds within
      macromolecules and the lipid phase, hydration of all polar groups with the
      appearance of water with high dielectric constant thus making possible the
      lateral diffusion within the membrane and realization, through water
      participation, of conditions within organelles and cells required for the process
      regulation at these levels. The mechanism of water action on various membrane
      components and their dynamics at each stage are discussed, as well as the effect
      of different types of motion on the efficiency and regulation of electron
      transport in the photosynthetic chain of the membranes studied.

PMID- 9257279
TI  - Stereoscopic analysis of microtubule pattern around the centrosome in interphase
      PK cells after treatment with taxol and nocodazole.
AB  - In the interphase PK cells, more than 85% of microtubules radiating from the
      centrosome were not longer than 1.5 microns. A half of microtubules had their
      proximal ends free. After nocodazole treatment (20 microM), the number of
      microtubules attached to the centrosome decreased by 20% after 10 min of
      treatment, remained the same after 20 min of treatment, and increased after 60
      min of nocodazole treatment slightly above the control level. After 5 and 60 min
      of treatment, the number of attached microtubules with the length over 0.7 micron
      increased twice as compared to the control level. During the first 20 min of
      nocodazole treatment, the immunofluorescent staining of cells with antibodies to
      gamma-tubulin was the same as in the control cells. The number of free
      microtubules decreased fourfold during the first 5 min, then it decreased slowly
      (for 20 min) and remained at the same level after 60 min. After 10 min of taxol
      (12 microM) treatment, the number of attached and free microtubules increased
      more than two times, whereas the number of attached microtubules with the length
      over 0.7 micron increased more than tenfold. After 15 min of treatment, the
      number of attached microtubules was slightly higher, and the number of free
      microtubules was half of the control level. After 20-60 min of treatment, the
      number of microtubules of all types decreased. Thus, upon the nocodazole
      treatment, the microtubules attached to the centrosome were more resistant to
      depolymerization: however, these microtubules were the most reactive to taxol
      treatment. The data obtained suggest that (a) in PK cells, the centrosome
      attached microtubules occupy not all of the existing templates; (b) during
      prolonged treatment with inhibitors, the centrosome performed the compensatory
      reaction-the inhibition of microtubule assembly results in the decrease in the
      number of active templates on the centrosome; the inhibition of microtubule
      depolymerization results in the inactivation of hitherto active reserve
      templates. The microtubules formed on the centrosome within the first minutes
      disengage from it and then leave the chromosomal region.

PMID- 9257280
TI  - The kinetic characteristics of the L-type calcium channels in cardiocytes of
      hibernators. 1. Development of a kinetic model.
AB  - The present paper described the experimental and theoretical investigations of
      the kinetic characteristics of the L-type Ca2+ channels in ground squirrels
      Citellus undulatus in two different physiological states (hibernation and
      spontaneous arousal). The perforated patch-clamp method was used in the
      experiments. It is shown that the potential-dependent Ca2+ current in isolated
      cardiocytes from hibernating animals is strongly inhibited during hibernation. An
      attempt was made to describe the kinetics of Ca2+ currents by the modified
      Hodgkin-Huxley equations. The experimental current traces are compared to the
      nonstationary solutions of the modified model, and the model parameters were
      found by optimization methods. It is shown that the simple dmfn model, where d is
      activation, f is inactivation, can not be used to describe the experimental
      characteristics at any power values m and n. Analysis of other models based on
      the conception of independence of activation and inactivation processes showed
      that in both physiological states-hibernation and spontaneous arousal-Ca2+
      current was described by the model d2f1(2)f2, where d is activation, f1 and f2
      are slow (f1-type) and fast (f2-type) inactivations of the channel.

PMID- 9257281
TI  - Involvement of erythrocyte membrane proteins in temperature-induced disturbances
      of the permeability barrier.
AB  - The ion permeability of human erythrocyte membrane displays two maxima at 48-52
      degrees C and 62-67 degrees C [6, 8]. Both these independent maxima were
      investigated in modified membranes in order to elucidate the participation of the
      main types of membrane proteins. The modification protocols included the
      bilateral proteolytic digestion of membranes with 2-20 micrograms/ml trypsin,
      denaturation of the peripheral protein spectrin by exposing the membranes to 50
      degrees C for 4 min or 1.5 M urea for 20 h, and preparation of the inside-out
      vesicles depleted of main peripheral proteins. Only the second maximum was
      registered in these membranes. Also, both maxima were absent in the unilamellar
      liposomes prepared from lipids extracted from intact membranes. The results
      indicate that different types of proteins were involved in the two disturbances:
      peripheral proteins (mainly spectrin)--in the first one and part of integral
      proteins-in the second. The different sensitivities of the disturbances to local
      anesthetics, protein thermostabilizers, n-alcohols, and detergents correlated
      with this conclusion. A correlation between the peak temperature of the second
      disturbance and the sphingomyelin content in the membrane of mammalian
      erythrocytes was also shown.

PMID- 9257282
TI  - A possible role of cold-induced ionic stress in cold-induced cell death.
AB  - Analysis of experimental results and published data within the framework of the
      suggested mathematical model of ion-osmotic homeostasis revealed the dependence
      of a variety of cell parameters on temperature. It was shown that the cold
      induced drastic increase in the basal concentration of cytoplasmic Ca was
      determined, on the one hand, by the suppression of transport processes
      responsible for Ca removal from the cytoplasm, and, on the other hand, by the
      increase of calcium fluxes, both from the outer medium and from cell organelles.
      The cold-induced variation in the ratio of permeabilities for Na and K ions was
      found, which can be due to the activation of different calcium- and potential
      dependent channels or by formation of membrane defects. Besides the flow of
      calcium ions through appropriate selective channels, its delivery into the
      cytosol through membrane defects actively induced by cell cooling can not be
      excluded. Formation of nonselective transmembrane channels was promoted by lipid
      peroxidation and proteolysis induced by an increase in the basal concentration of
      calcium. The new approaches to protecting the cell from cold injury are
      discussed.

PMID- 9257283
TI  - Effect of phytohormones on ATP-dependent accumulation of Ca2+ in plasma membrane
      vesicles from tubers of potato Solanum tuberosum L.
AB  - A membrane fraction enriched with plasmalemma vesicles was isolated from potato
      tubers using the polyethylene glycol 3550--dextran T-500 phase partitioning. As
      judged by the activities of enzyme markers of the inner plant cell membranes, the
      fraction consisted of plasmalemma vesicles with tonoplast vesicle contamination
      and contained no mitochondrial membranes, endoplasmic reticulum or Golgi
      apparatus. Under conditions of total inhibition of nitrate-sensitive ATPase of
      the tonoplast, the vesicles of the fraction obtained exhibited the ATP-dependent
      accumulation of Ca2+. It was inhibited to various extents by Na3VO4, dicyclohexyl
      carbodiimide (DCCD) and phytohormones--gibberellic acid (GA3), abscisic acid
      (ABA) and indoleacetic acid (IAA), whereas kinetin rendered a stimulating effect.
      The action of phytohormones on the accumulation of Ca2+ in the presence of DCCD
      or Na3VO4 suggests that GA3, ABA and kinetin affect the activity of Ca2+,Mg(2+)
      ATPase, whereas IAA most probably stimulates the efflux of Ca2+ from the vesicles
      or the separation of membrane-bound Ca2+.

PMID- 9257284
TI  - Inactivation of brain Na+,K(+)-ATPase catalytic subunit isoforms by sodium
      dodecyl sulfate.
AB  - Persistence of the brain and kidney Na+,K(+)-ATPase isozymes to SDS inactivation
      under different time and temperature conditions of microsome extraction with the
      detergent was compared. In contrast to enzyme preparations from medulla oblongata
      the higher sensitivity of the Na+,K(+)-ATPase alpha-isoform (in comparison to
      alpha +) to SDS inactivation accompanied by its, at least, partial removal from
      the membrane was found in the preparations from cerebral cortex. This difference
      in the sensitivity to SDS was eliminated after extraction of microsomes with the
      detergent at 37 degrees C. The interpretation of the results is based on the
      assumed differences in the structural organization of the boundary lipids of the
      neuronal Na+,K(+)-ATPase catalytic subunit isoforms.

PMID- 9257285
TI  - A stochastic simulation of direct ion passage through a sodium channel.
AB  - Direct passage of alkali metal cations through a model transmembrane sodium
      channel is simulated by means of the Brownian dynamic technique. The Langevin
      version of the Brownian motion in the diffusive limit and with the finite
      difference equation approximation was used. Ion trajectories, single channel
      unidirectional ionic fluxes, average times of direct passage, as well as
      conductivities, were calculated. The microscopic theory of channel selectivity is
      presented.

PMID- 9257286
TI  - Changes in the redox potential and catalase activity of Mn2+ ions during
      formation of Mn-bicarbonate complexes.
AB  - Changes in the redox potentials of Mn2+ ions and Mn-bicarbonate complexes were
      studied due to their possible participation in the photosynthetic oxidation of
      water in plant photosystem 2 and in H2O2 decomposition. Electrochemical oxidation
      of Mn2+ ions was demonstrated by voltammetry on a platinum electrode in 0.1 M
      LiClO4 solution at a potential of 1.19 V (vs NHE). When NaHCO3 was added, the
      oxidation peak of Mn2+ ions disappeared. New oxidation peaks appeared at 0.92 V
      and 0.63 V which corresponded to the oxidation of Mn(HCO3)+ and Mn(HCO3)2,
      respectively, generated by complex formation between Mn2+ and HCO3- ions. The
      effect of the Mn(2+)-bicarbonate complex on H2O2 redox decomposition was studied.
      It was shown that the addition of MnSO4 to the H2O2 solution did not affect the
      H2O2 oxidation peak height thereby indicating the absence of H2O2 decomposition
      by Mn2+ ions. At the same time, subsequent addition of NaHCO3 resulted in the
      disappearance of the oxidation peaks of both H2O2 and Mn2+. As at pH 7 the
      thermodynamic potential of H2O2 reduction is 1.1 V and the Mn2+ oxidation
      potential is 1.19 V, the redox reaction between them is hampered. Formation of
      the Mn(2+)-bicarbonate complex shifted the Mn2+ oxidation potential to 0.63 V,
      thereby inducing the decomposition of H2O2. It is suggested that the decrease in
      the Mn2+ oxidation potential resulting from the formation of the bicarbonate
      complex determines the bicarbonate capability to enhance the Mn2+ ability to
      donate electrons for PS 2 reaction centres.

PMID- 9257287
TI  - Electrofusion of Escherichia coli cells.
AB  - Bacterial cell fusion was observed under conditions optimal for highly efficient
      electrotransformation of untreated Escherichia coli cells. E. coli clones
      possessing the joint phenotype were found after electric treatment of genetically
      marked parental strains. The phenotypes of the clones segregated due to a
      subsequent cultivation of the clones, whereas some of them turned out to be
      recombinants. Electron microscopy carried out 1 h after electric treatment of the
      cells revealed physical contacts between the cells being in parallel arrangement.
      The electrofusion processes detected are important for the estimation of
      electrotransformation efficiency. A possibility to use electrofusion of untreated
      bacterial cells for in vivo transfer of plasmid and chromosomal DNAs is
      discussed.

PMID- 9257288
TI  - Participation of biological membranes in colloidal gold transformation by
      Micrococcus luteus cells.
AB  - Methods of biochemical and physicochemical analysis were applied for studying the
      role of Micrococcus luteus cell structure in gold accumulation. It was shown that
      membrane proteins were the main factors in this process. Moreover, different
      quinones played the main role in the redox transformation of gold.

PMID- 9257289
TI  - Reconstitution of the zone-block model of biomembranes. 3. Synthesis and
      investigation of the structure of phosphatidylcholine analog isobutyl-2
      (trimethylammonia)ethyl phosphate in its monohydrate crystals and monohydrate
      complexes with isobutanol.
AB  - An isobutyl analog of phosphatidylcholine--isobutyl-2-(trimethylammonia)ethyl
      phosphate (IPC)--was synthesized to accomplish the physical reconstitution of the
      zone-block model of biomembranes. X-ray analysis was used to study the IPC
      monohydrate (IPC.H2O) crystals grown from water or dimethylformamide with 2%
      water and the IPC.H2O complex with isobutanol (IPC.H2O.IB) formed by IPC
      crystallization from isobutanol with 0.5% water. The two compounds were shown to
      belong to the monoclinic syngony (Sp. gr. P2(l)/a): IPC.H2O-a = 11.075(4), b =
      9.679(3), c = 13.921(5) A; beta = 110.61(4) degrees, Z = 4; IPC.H2O.IB-a =
      11.370(6), b = 9.397(5), c = 18.12(1) A, beta = 99.42(5) degrees, Z = 4. In
      IPC.H2O crystals, IPC molecules formed chains due to the system of hydrogen bonds
      between water molecules and IPC phosphate groups. In turn, ionic bonds between
      trimethylammonium and phosphate groups of the bipolar heads made these chains to
      form layers. Another system of ionic bonds (also between -N+(CH3)3 and -O-P = O
      groups) arranged the layers in a bilayer structure. The bonds were formed between
      the pairs of molecules oppositely directed and located in neighbouring
      monolayers. The structure of the bilayer in IPC.H2O.IB crystals was similar. The
      only difference was the presence of isobutanol molecules between the IPC isobutyl
      radicals. C-OH groups of isobutanol formed hydrogen bonds with water molecules.
      However, the interlayer gaps in these two cases differed significantly. In
      IPC.H2O, the bilayers partially overlapped, whereas in IPC.H2O.IB, they were
      located at a considerable distance. The structures of the investigated compounds
      confirm in principle the possibility of the formation of ionic bonds between
      trimethylammonium and phosphate groups within the bilayer as well as in the
      interzonal region with apolar radicals that was predicted by the zone-block model
      of biomembrane. However, the phosphocholine heads were parallel but not
      perpendicular (as presumed in the model) to the bilayer plane.

PMID- 9257290
TI  - The effect of low-intensity laser irradiation on the hydrolytic activity of
      vacuolar membrane proton pumps.
AB  - The effect of low-intensity irradiation by a helium-neon laser on the hydrolytic
      activity of the vacuolar membrane proton pumps has been studied. The maximum
      effect was found for the 3 min irradiation from a close distance (0.3 m);
      moreover, the PPase activity increased by 33%, whereas the ATPase activity was
      inhibited by 44%. The effect described is suggested to be due to different
      conformations of the enzymes in the membrane and their different physiological
      roles.

PMID- 9257291
TI  - Testing gene therapy vectors in healthy volunteers.

PMID- 9257292
TI  - DNA repair 'test' for Alzheimer's disease?

PMID- 9257293
TI  - 'Genetic surgery' for vascular grafts.

PMID- 9257294
TI  - Growth factors, signalling and cancer.

PMID- 9257295
TI  - Cancer vaccines: challenges and potential solutions.
AB  - Almost a century has passed since immunotherapy of cancer was first attempted
      using cancer immunogens (vaccines); however, its clinical impact remains modest.
      Although initial concerns about a lack of human tumor antigens have decreased,
      prevailing issues include inefficient procedures for immunization and
      downregulated expression of major histocompatibility complex (MHC) class I
      molecules in tumor cells. While immunization can be improved, deficient MHC class
      I expression remains a problem, because it hampers the ability of tumor cells to
      present antigens for killing by CD8+ T cells. These are the major mediators of
      tumor destruction, and they have little or no activity against antigen-negative
      bystander cells. However, there are reasons to be optimistic that therapeutic
      vaccination against cancer antigens might become a reality at last.

PMID- 9257296
TI  - Drugs from the sea: harvesting the results of aeons of chemical evolution.
AB  - Despite the recent development of combinatorial chemistry for the rapid
      generation of thousands of new chemicals, the pharmaceutical industry still looks
      to the natural environment to uncover novel compounds that extend the boundaries
      of our chemical imagination. The terrestrial environment has been mined for such
      compounds for many years with great success. Now the world's oceans are beginning
      to yield hidden treasures. Many of these chemicals are structurally complex,
      stretching the prowess of modern organic chemists to their limits as they attempt
      to mimic the synthetic versatility of nature. In the future, these marine
      compounds are likely to yield entirely new classes of drugs that will be a
      valuable contribution to our ability to treat human disease.

PMID- 9257297
TI  - Lipocortin 1: a second messenger of glucocorticoid action in the hypothalamo
      pituitary-adrenocortical axis.
AB  - The secretion of hydrocortisone by the adrenal cortex is crucial in balancing the
      reaction of the body to injury or stress. In the periphery, hydrocortisone
      inhibits inflammation, downregulates the immune system and produces many other
      crucial physiological and metabolic changes. Within the neuroendocrine system,
      hydrocortisone inhibits the release of adrenocorticotrophic hormone (and other
      pituitary hormones), thereby governing its own secretion. The manifold actions of
      hydrocortisone are mediated through induction or repression of many genes but one
      pathway, mediated by the inducible protein lipocortin 1 (LC-1, also known as
      annexin 1), mediates several important effects both within the hypothalamo
      pituitary-adrenocortical axis itself and in the periphery.

PMID- 9257298
TI  - Thrombophilia: an expanding group of genetic defects that predispose to
      thrombosis.
AB  - Thrombophilia is a term recently coined to describe the increased tendency of
      some patients to develop thrombosis. Although the term was originally used as a
      clinical description, the abnormalities of the coagulation system responsible can
      now be identified in approximately 50% of cases of thrombosis. Many of these
      disorders are hereditary and it is this group that are generally referred to as
      thrombophilia. Recent studies have begun to establish the mutations responsible
      for the hereditary thrombophilias and to assess their interactions with one
      another. However, it is also clear that many other factors remain undiscovered.

PMID- 9257299
TI  - The role of adhesion molecules in multiple sclerosis: biology, pathogenesis and
      therapeutic implications.
AB  - Multiple sclerosis (MS) remains a major challenge to basic and clinical research.
      Some of the pivotal immune mechanisms operating in this chronic inflammatory
      disease have recently been characterized but development of more satisfactory
      treatment still requires a better understanding of the pathogenesis and
      immunopathology of MS. Adhesion molecules are known to be of fundamental
      importance in autoimmune disease, and a variety of new therapeutic approaches to
      target them have emerged in the past few years; they should open new avenues to
      improve the outcome of this disabling disease.

PMID- 9257300
TI  - Contralateral and ipsilateral microsurgical approaches to carotid-ophthalmic
      aneurysms.
AB  - OBJECTIVE: The vicinity of carotid-ophthalmic aneurysms to the roof of the
      cavernous sinus, to the anterior clinoid process, and to the optic nerve or the
      optic chiasm requires well-defined surgical techniques. Although microsurgical
      techniques with ipsilateral direct approaches to these aneurysms have been
      described in detail, studies about contralateral strategies for the microsurgical
      treatment of carotid-ophthalmic aneurysms are rare and are mainly confined to
      case reports. The aim of this study is to describe how to decide on the
      ipsilateral and contralateral microsurgical approaches to such aneurysms and to
      demonstrate the surgical techniques for the ipsilateral and contralateral
      exposure of carotid-ophthalmic aneurysms. METHODS: In a series of 51 patients
      with 58 aneurysms of the ophthalmic segment of the internal carotid artery, nine
      patients with 10 aneurysms (4 large aneurysms, 6 small aneurysms) were treated
      via a contralateral microsurgical approach after careful preoperative planning.
      Preoperative planning was based on the analysis of clinical and radiographic
      data, including cranial computed tomography, magnetic resonance imaging, magnetic
      resonance angiography, and conventional cerebral angiography. RESULTS: The
      postoperative results were good in 38 (75%) of the patients, fair in 2 (4%), and
      poor in 3 (6%); 8 (15%) of the patients died after surgery. The postoperative
      follow-up was 4 months to 10 years. Postoperatively, 15 of 19 patients with uni-
      or bilateral visual deficits or visual field defects improved, 3 of the 19
      patients experienced postoperative impairment of visual function, and 1 of the 19
      patients had an unchanged visual field deficit. Visual impairment or unchanged
      visual function was observed in patients who underwent ipsilateral approaches,
      which was possibly caused by inappropriate intraoperative retraction of the optic
      nerve or chiasm. In all patients presenting with preoperative visual deficits who
      were treated via contralateral approaches, visual function improved in the
      postoperative course. CONCLUSION: Giant carotid-ophthalmic aneurysms that are
      eligible for surgical treatment as well as small and large aneurysms dislocating
      the optic nerve or the chiasm superomedially or medially should be approached via
      ipsilateral craniotomies. It is recommended that small and large aneurysms of the
      carotid-ophthalmic segment originating medially, superomedially, or superiorly,
      displacing the optic nerve or the chiasm superiorly, superolaterally, or
      laterally, be approached via contralateral craniotomies.

PMID- 9257302
TI  - Cerebral arterial spasm after penetrating craniocerebral gunshot wounds:
      transcranial Doppler and cerebral blood flow findings.
AB  - OBJECTIVE: The goals of the study were to determine the incidence and time course
      of cerebral arterial spasm in patients with penetrating craniocerebral gunshot
      wounds, to study the relationship between vasospasm and subarachnoid hemorrhage
      (SAH) in these patients, and to evaluate the effects of vasospasm on outcome.
      METHODS: Thirty-three patients with craniocerebral gunshot wounds underwent
      computed tomography at admission and then underwent transcranial doppler
      ultrasonography (TCD). Velocities in the middle cerebral artery and the
      extracranial internal carotid artery were measured. Vasospasm was defined as a
      middle cerebral artery velocity greater than 120 cm per second and a hemispheric
      index (ratio of middle cerebral artery to internal carotid artery velocity)
      greater than 3. Intravenous xenon-133 cerebral blood flow (CBF) studies were
      performed for 10 patients. RESULTS: TCD was initiated, on average, 1.1 days after
      injury; 205 studies (mean, 6.3 studies/patient) were performed 0 to 33 days after
      injury. TCD showed vasospasm in 14 patients (42.4%). Xenon-133 studies performed
      within 24 hours of TCD measurements indicating spasm demonstrated normal or low
      CBF in three of five patients with spasm, ruling out hyperemia as the cause of
      elevated flow velocities in these three patients. Seven patients had unilateral
      vasospasm, and seven had bilateral spasm. Vasospasm was most prominent from Days
      5 through 11. Vasospasm was distributed across all levels of injury severity, as
      defined by the Glasgow Coma Scale. Initial computed tomographic scans
      demonstrated SAH in all 14 patients with vasospasm but in only 9 of 19 without
      spasm (100 versus 47%, P < 0.0001, binomial distribution probability test).
      Outcomes for patients with vasospasm were slightly worse than for those without
      spasm (35.7 versus 47.4% good outcomes, respectively); however, this difference
      did not reach statistical significance (P = 0.12). CONCLUSION: These findings
      demonstrate that delayed cerebral arterial spasm is a frequent complication in
      patients with craniocerebral gunshot wounds and is strongly associated with SAH.
      The frequency, time course, and severity of spasm are comparable with those
      observed with aneurysmal SAH and traumatic SAH caused by closed head injury. This
      study offers new insights into the hemodynamic pathophysiology after gunshot
      wounds to the brain and suggests that increased vigilance for vasospasm may be of
      benefit.

PMID- 9257301
TI  - Coagulative and fibrinolytic activation in cerebrospinal fluid and plasma after
      subarachnoid hemorrhage.
AB  - OBJECTIVE: Intrathecal fibrinolytic therapy has been used as one of the
      anticerebral vasospasm (VS) preventative therapies in patients with subarachnoid
      hemorrhage (SAH). However, the changes in coagulation and fibrinolysis in the
      blood and cerebrospinal fluid (CSF) after SAH remain unknown. METHODS: Fifty
      patients with SAH caused by ruptured cerebral aneurysms were studied
      postoperatively to detect the serial changes of the thrombin-antithrombin III
      complex, active plasminogen activator inhibitor (PAI)-1, and tissue plasminogen
      activator (tPA)-PAI complex (tPA-PAI) activities in the plasma and CSF collected
      from cisternal drainage catheters. RESULTS: The CSF levels of all parameters and
      plasma PAI-1 levels were significantly higher in patients with severe SAH than in
      those with mild SAH. There was no relationship between the CSF and plasma levels
      of these parameters (except the CSF levels of tPA-PAI) and the initial
      neurological statuses. The CSF PAI-1 levels increased to greater than 20 ng/ml
      near the time of the occurrence of cerebral VS, whereas they remained below 20
      ng/ml in patients without VS. The CSF tPA-PAI levels showed the highest peak near
      the time of VS remission. The CSF PAI-1 and tPA-PAI levels were significantly
      lower in patients with good outcomes than in those with poor outcomes.
      CONCLUSION: Both the coagulative and fibrinolytic systems were activated in the
      CSF and plasma after SAH in correlating to the amount of SAH clot. The
      intrathecal administration of fibrinolytic agents should be started early after
      surgery, before CSF PAI-1 levels increase, for patients with severe SAH. Patients
      with CSF PAI-1 levels greater than 20 ng/ml experienced high incidence of VS and
      poor outcomes.

PMID- 9257303
TI  - Transcutaneous carbon dioxide measurement after craniotomy in spontaneously
      breathing patients.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of
      postoperative hypercarbia in patients undergoing intracranial neurosurgery.
      Postoperative hypercarbia is a well-recognized cause of postoperative morbidity.
      METHODS: Sixty-four patients undergoing craniotomy were monitored in the first 36
      postoperative hours using transcutaneous CO2 monitoring. We collected and
      analyzed demographic data, complete medical histories and examinations, and
      details of surgery, anesthesia, and postoperative progress. The accuracy of the
      transcutaneous CO2 monitoring was evaluated by comparison with arterial blood gas
      CO2. INSTRUMENTATION: The "TINA" TCM3 Transcutaneous CO2 Monitor (Radiometer,
      Copenhagen, Denmark) was used. RESULTS: Thirty-nine patients (61%) developed no
      hypercarbia. Nineteen patients (30%) developed mild to moderate hypercarbia (46
      59 mm Hg) and six patients (9%) developed severe hypercarbia (60 mm Hg or
      greater). Statistically significant differences were observed between the
      severely hypercarbic group and the other two groups combined, as follows: a
      higher incidence of preoperative and postoperative seizures, a lower average
      postoperative Glasgow Coma Scale score, a higher incidence of reintubation and
      ventilation, and a higher degree of intraoperative brain disturbance. Analysis of
      transcutaneous CO2 measurements and time-matched arterial blood gas CO2
      measurements revealed an acceptable accuracy of the transcutaneous method.
      CONCLUSION: this study demonstrates that, in routine neurosurgical practice, a
      subgroup of patients are at risk of developing postoperative hypercarbia, which
      may be more common than is generally recognized and will not usually be detected
      by routine postoperative monitoring. Transcutaneous CO2 monitoring is a useful
      technique that may impact management decisions.

PMID- 9257304
TI  - Occipital condyle fractures.
AB  - OBJECTIVE: Occipital condyle fractures (OCFs) are infrequently recognized. Three
      recent cases of OCF in our center prompted a review of the incidence, clinical
      presentation, diagnosis, and treatment of this entity. METHODS: A retrospective
      review of medical records and radiographic results was performed for 93 of 316
      consecutive patients who were victims of trauma, who presented at the Toronto
      Hospital during a 13-month period, and who had undergone computed tomography of
      the occiput. RESULTS: A review of the literature regarding OCF revealed that
      cranial nerve deficits occurred in 31% of the patients with OCFs; of those, the
      deficits were delayed in 38%. Three new cases of OCF, with neck pain but without
      cranial nerve deficits, have been reported. The cervical spine x-rays revealed
      nothing abnormal in 96% of the reported cases. In our retrospective review,
      asymptomatic OCF was revealed by computed tomography for 1 of the 93 patients.
      CONCLUSION: OCF is a diagnostic challenge. We suggest that computed tomographic
      scans of O-C2 be obtained in the following circumstances: presence of lower
      cranial nerve deficits, associated head injury or basal cranial fracture, or
      persistent severe neck pain despite normal radiographic results. We propose a new
      classification system for the management and treatment of OCF based on the
      stability of the O-C1-C2 joint complex reflected by the presence of displacement
      of the condyle, computed tomographic or radiographic evidence of O-C1-C2
      instability, and magnetic resonance evidence of ligamentous injury. OCFs are
      divided into the following types: Type 1 (stable), undisplaced fracture; Type 2A
      (stable), displaced fracture with no ligamentous instability; and Type 2B
      (unstable), displaced fracture with ligamentous instability.

PMID- 9257305
TI  - Surgical treatment of neoplasms associated with medically intractable epilepsy.
AB  - OBJECTIVE: Surgical treatment in patients with brain tumors and medically
      intractable epilepsy is aimed at the removal of the neoplasm and complete seizure
      control. However, an adequate surgical approach is still controversial. This
      study was designed to analyze the factors for the optimum surgical treatment of
      these patients. METHODS: The clinical, electrophysiological, operative, and
      histopathological data of 146 consecutive patients who underwent surgery between
      November 1987 and May 1995 for intrinsic brain tumors and pharmacoresistant
      epilepsy were evaluated. RESULTS: The majority of the tumors were located in the
      temporal lobe (n = 116) and involved the cortical gray matter. The most frequent
      tumors were gangliogliomas (n = 65), pilocytic astrocytomas (n = 21), and
      dysembryoplastic neuroepithelial tumors (n = 19). All but three tumors (98%) were
      of low histopathological grade (World Health Organization Grades I or II). The
      biological behavior of the tumors was strikingly indolent, as indicated by a long
      preoperative history of chronic seizures (mean, 14 yr). In all cases, complete
      resection of the tumor, including the epileptogenic area (as determined by
      noninvasive and/or invasive recordings of the zone of seizure onset and
      persistent interictal activity), was intended. Complications were encountered in
      11 cases (8%). However, no patient died and there was no permanent morbidity. Of
      the 124 patients who had postoperative follow-up examinations more than 6 months
      after resection, 71% were seizure-free, 11% had no more than two seizures per
      year, 13% showed a reduction of seizure frequency of at least 75%, and 5% had no
      appreciable reduction in seizure frequency. CONCLUSION: The data indicate that
      neoplasms associated with medically intractable epilepsy constitute a distinct
      clinicopathological group of tumors that arise in young hosts, involve the
      cortex, and exhibit indolent biological behavior for many years. Complete
      surgical removal of these tumors, including the epileptogenic area, can achieve
      excellent seizure control.

PMID- 9257306
TI  - Proton spectroscopy of suprasellar tumors in pediatric patients.
AB  - OBJECTIVE: Magnetic resonance imaging and computed tomography provide good
      anatomic detail of suprasellar tumors in pediatric patients but are not able to
      predict histology in many cases. Proton magnetic resonance spectroscopy provides
      metabolic data that may add to diagnostic specificity. We preoperatively
      performed localized proton magnetic resonance spectroscopy on pediatric patients
      with suprasellar tumors and correlated the results with the histological
      findings. Cyst fluid obtained from patients with craniopharyngiomas was studied
      with high-resolution magnetic resonance spectroscopy to better understand the in
      vivo data. METHODS: Nineteen patients aged 1 to 21 years underwent spectroscopy.
      Surgical pathological samples were obtained from 14 patients. In each of five
      patients, the presence of a solid chiasmatic mass in addition to clinical
      evidence of neurofibromatosis Type I allowed the presumptive diagnosis of
      chiasmatic astrocytoma. Thus, the study population included 6 patients with
      craniopharyngiomas, 10 with chiasmatic/hypothalamic astrocytomas, and 3 with
      pituitary adenomas. The data obtained were compared with those of healthy brain
      from age-matched participants. RESULTS: Spectroscopy was specific for the
      diagnosis. All craniopharyngiomas showed a dominant peak at 1 to 2 ppm,
      consistent with lactate or lipids, with trace amounts of other metabolites. This
      was confirmed using high-resolution spectroscopy. Chiasmatic gliomas showed a
      profile of choline, N-acetylaspartate, and creatine, and the choline:N
      acetylaspartate ratio was 2.6 +/- 1.3, compared with 0.7 +/- 0.3 for samples of
      healthy brain (t test, P = 0.0003). Pituitary adenomas showed only a choline peak
      or no metabolites at all. CONCLUSION: Proton spectroscopy may be helpful in
      supplementing standard imaging for the preoperative diagnosis of three types of
      suprasellar tumors that are common in pediatric patients.

PMID- 9257307
TI  - Radiosurgical lesions in the normal human brain 17 years after gamma knife
      capsulotomy.
AB  - OBJECTIVE: To our knowledge, this is the first long-term follow-up study of high
      dose single-session irradiation to the human brain and provides new data
      concerning late tissue reactions after irradiation to small target volumes. The
      long-term lesional brain changes in 14 patients subjected to bilateral gamma
      knife capsulotomy for otherwise intractable anxiety disorders were
      retrospectively analyzed by magnetic resonance imaging. METHODS: The prototype
      gamma unit was used for the radiosurgical procedure, and the collimators provided
      rectangular cross-sectional fields with an anteroposterior diameter of 3 mm and a
      transverse diameter of 5 or 11 mm. Maximum target doses were 120 to 180 Gy.
      Magnetic resonance imaging was performed 15 to 18 years (mean, 17 yr) after
      treatment, and dose-volume histograms were calculated for the dose distributions.
      RESULTS: One patient had been irradiated twice on one side. In all but one of the
      remaining 27 targets, lesions with a volume of less than 100 mm3 were revealed by
      magnetic resonance imaging. The volumes of the lesions were confined within the
      volume corresponding to a minimum dose of approximately 110 Gy, with one
      exception. In one of three targets receiving a maximum dose of 120 Gy, no lesion
      was detected. There were no late radiation effects such as cyst formations,
      telangiectasias, hemorrhagic infarctions, or neoplasms. CONCLUSION: This
      investigation indicates that a minimum dose of 110 Gy, with the currently used 4
      mm collimator, to the edge of the target volume is required to create a lesion.
      The results prove that gamma knife surgery can be used in functional neurosurgery
      for producing small permanent lesions in the normal human brain.

PMID- 9257308
TI  - Computer-assisted surgical planning for cerebrovascular neurosurgery.
AB  - OBJECTIVE: We used three-dimensional reconstructed magnetic resonance images for
      planning the operations of 16 patients with various cerebrovascular diseases. We
      studied the cases of these patients to determine the advantages and current
      limitations of our computer-assisted surgical planning system as it applies to
      the treatment of vascular lesions. METHODS: Magnetic resonance angiograms or thin
      slice gradient echo magnetic resonance images were processed for three
      dimensional reconstruction. The segmentation, based on the signal intensities and
      voxel connectivity, separated each anatomic structure of interest, such as the
      brain, vessels, and skin. A three-dimensional model was then reconstructed by
      surface rendering. This three-dimensional model could be colored, made
      translucent, and interactively rotated by a mouse-controlled cursor on a
      workstation display. In addition, a three-dimensional blood flow analysis was
      performed, if necessary. The three-dimensional model was used to assist in three
      stages of surgical planning, as follows: 1) to choose the best method of
      intervention, 2) to evaluate surgical risk, 3) to select a surgical approach, and
      4) to localize lesions. RESULTS: The generation of three-dimensional models
      allows visualization of pathological anatomy and its relationship to adjacent
      normal structures, accurate lesion volume determination, and preoperative
      computer-assisted visualization of alternative surgical approaches. CONCLUSION:
      Computer-assisted surgical planning is useful for patients with cerebrovascular
      disease at various stages of treatment. Lesion identification, therapeutic and
      surgical option planning, and intraoperative localization are all enhanced with
      these techniques.

PMID- 9257310
TI  - A review of stress ulcer prophylaxis in the neurosurgical intensive care unit.
AB  - STRESS ULCERS OCCUR frequently in intensive care unit patients who have
      intracranial disease. After major physiological stress, endoscopic evidence of
      mucosal lesions of the gastrointestinal tract appears within 24 hours of injury;
      17% of these erosions progress to clinically significant bleeding.
      Gastrointestinal hemorrhage has been associated with mortality rates of up to
      50%. The pathogenesis of stress ulcers may not be completely understood, but
      gastric acid and pepsin appear to play significant roles. Antacids, H2
      antagonists, and sucralfate are effective prophylactic agents in the
      medical/surgical intensive care unit. Appropriate therapy for neurosurgical
      patients remains unclear, however. This review summarizes the current literature
      regarding the pathogenesis and therapy of stress ulcers in neurosurgical
      patients.

PMID- 9257309
TI  - Preservation of pudendal afferents in sacral rhizotomies.
AB  - OBJECTIVE: To assess the effectiveness of pudendal afferent mapping as a tool to
      minimize the risk of postoperative bowel, bladder, and sexual dysfunction in
      patients undergoing selective posterior rhizotomies in whom the S2 roots are
      candidates for rhizotomy. METHODS: One-hundred fourteen children with the
      diagnosis of cerebral palsy and debilitating spasticity were selected to undergo
      selective posterior rhizotomies at New York University Medical Center during 1991
      through 1995. There were 72 male and 42 female patients with a mean age of 3.8
      years. At the time of surgery, none of the patients had clinically relevant
      bladder dysfunction. Dorsal root action potentials were recorded intraoperatively
      to map the distribution of pudendal afferent fibers in S1-S3 roots bilaterally
      before performing the rhizotomies. RESULTS: Pudendal afferent mapping was
      successful in 105 of 114 patients. In the majority of these patients (56%), the
      distribution was asymmetrical. S1 roots contributed 4%, S2 roots 60.5%, and S3
      roots 35.5% of the overall pudendal afferent activity. The pudendal afferent
      distribution was often confined to a single level in 18% of the patients or even
      to a single root in 7.6%. Fifty-six percent of the pathologically responding S2
      roots during rhizotomy testing were preserved because of the significant afferent
      activity, as demonstrated during pudendal mapping. None of the 105 patients so
      mapped developed long-term bowel or bladder complications. CONCLUSIONS: Pudendal
      afferent mapping identifies S2 roots that carry a significant number of fibers
      involved with genital sensation. The preservation of such roots during surgical
      procedures may be important for sexual function and may also contribute to
      decreasing postoperative bladder and bowel disturbances.

PMID- 9257311
TI  - Rotational vertebral artery occlusion: a mechanism of vertebrobasilar
      insufficiency.
AB  - OBJECTIVE: Symptomatic dynamic changes in blood flow secondary to vertebral
      artery compression with rotational head motion are evaluated in a series of
      patients as a cause for posterior circulation transient ischemic attacks. These
      cases are classic examples of rotational vertebral artery occlusion and allow for
      the discussion of the anatomic basis, angiographic features, and treatment
      options. ILLUSTRATIVE CASES: In our series, symptoms of vertebrobasilar
      insufficiency were reproducible with rotational head movement. Compression of the
      vertebral artery was demonstrated angiographically. The correct site of occlusion
      of the vertebral artery was apparent only by dynamic angiography with progressive
      head rotation. All of the patients presented in the illustrative cases had
      occlusion at the C2 level; however, one patient had been previously misdiagnosed
      and another had an additional site of occlusion. The anatomic course of the
      vertebral artery is described in addition to the sites of rotational occlusion.
      CONCLUSION: Rotational vertebral occlusion is an important cause of
      vertebrobasilar symptoms, which may lead to permanent neurological deficit if
      left undiagnosed. Dynamic angiography is the established method of diagnosis.
      Great care must be taken to avoid misdiagnosing the site of occlusion or missing
      a second occlusive site. For this reason, it is crucial to have a thorough
      understanding of the anatomic course of the vertebral artery and the muscular and
      tendinous insertions, which may cause rotational occlusion. The decision for
      treatment must be based on the site of occlusion as well as the assessment of the
      patient as a surgical candidate. A review of the literature reveals that surgical
      treatment is effective and must be considered to avoid further morbidity.

PMID- 9257312
TI  - Application of antisense ribonucleic acid complementary to O6-methylguanine
      deoxyribonucleic acid methyltransferase messenger ribonucleic acid for therapy of
      malignant gliomas.
AB  - OBJECTIVE: A derivative of chloroethylnitrosoureas, 1-(4-amino-2-methyl-5
      pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), is a drug of choice
      for the chemotherapy of human malignant brain tumors. However, the cytocidal
      effect of ACNU is effectively repressed through repair of ACNU-mediated
      deoxyribonucleic acid lesions by O6-methylguanine-deoxyribonucleic acid
      methyltransferase (MGMT). Because a variety of human tumors, including brain
      tumors, contain high levels of MGMT activity, we investigated the effect of
      antisense ribonucleic acid (RNA) complementary to MGMT messenger RNA on ACNU
      resistance in tumor cells. METHODS: We established a stable ACNU-resistant clone,
      C6AR, from the rat glioma cell line C6 exposed to a stepwise increasing
      concentration of ACNU. We transfected a plasmid deoxyribonucleic acid-encoding
      antisense MGMT RNA under the control of the human metallothionein promoter into
      C6AR cells and determined the effect of the antisense RNA on ACNU resistance of
      tumor cells by a colony-forming efficiency assay. RESULTS: C6AR cells expressed
      abundant MGMT messenger RNA, although the transcription level of the MGMT gene in
      parental C6 cells was below the lower limits of detection under the same assay
      conditions. ACNU resistance of C6AR cells was significantly repressed by
      transfected gene-dependent antisense MGMT RNA expression that resulted in
      decreased survival of the tumor cells. CONCLUSION: ACNU resistance resulting from
      the expression of MGMT in rat glioma cells is significantly overcome by the
      expression of antisense MGMT RNA. This result suggests that the antisense MGMT
      RNA system might be a useful strategy for overcoming ACNU resistance in the
      treatment of intractable malignant gliomas.

PMID- 9257314
TI  - Endothelial cell expression of intercellular adhesion molecule 1 in experimental
      posthemorrhagic vasospasm.
AB  - OBJECTIVE: The exposure of large intracranial arteries to blood after an
      aneurysmal subarachnoid hemorrhage leads to a cascade of morphological and
      physiological changes in the vessels, a condition generally described as
      vasospasm. This response to the periadventitial deposition of blood is mediated
      in part by the endothelial layer of the vessel. This study was undertaken to
      examine the role of endothelial cell expression of intercellular adhesion
      molecule 1 (ICAM-1) in the initiation and regulation of this response. METHODS:
      The femoral artery model of vasospasm was used in rats (65 animals, 130
      arteries). In each rat, one artery was exposed to blood and the contralateral
      vessel was exposed to saline, so that each animal served as its own control.
      Animals were perfused and killed at sequential time points, from 1 hour to 20
      days after blood exposure. The vessels were examined immunohistochemically and
      histologically for the presence of ICAM-1 and morphological features of
      vasospasm, respectively. RESULTS: Endothelial cell ICAM-1 immunoreactivity was
      extensively increased in only the blood-exposed vessels, beginning 3 hours after
      clot placement and persisting for 24 hours. ICAM-1 immunoreactivity returned to
      baseline by 48 hours after blood exposure. The influx of inflammatory cells
      correlated directly with the time and location of increased ICAM-1 expression.
      Peak arterial remodeling was observed on the blood-exposed side 8 to 12 days
      after clot placement, as quantified by measurements of increased wall thickness,
      decreased lumen size, and increased collagen content. CONCLUSION: Endothelial
      cell ICAM-1 expression seems to be an early and specific signal used by a vessel
      in response to the deposition of blood periadventitially. This molecule may be a
      marker for vessels likely to undergo subsequent morphological remodeling and
      vasospasm.

PMID- 9257313
TI  - Preclinical testing of recombinant adenoviral herpes simplex virus-thymidine
      kinase gene therapy for central nervous system malignancies.
AB  - OBJECTIVES: Adenoviral gene transfer and killing efficiency using the thymidine
      kinase (TK)/ganciclovir (GCV) mechanism was evaluated in human cancer cells
      occurring as central nervous system tumors. The effectiveness of this approach
      was tested in vitro and in experimental models for brain tumor and leptomeningeal
      metastases in rats in vivo. Recombinant adenoviruses with different promoters
      were compared. METHODS: Adenoviral vectors harboring a marker (lacZ) or a TK gene
      were constructed. Transcription of genes was under the control of either the
      adenovirus Type 2 major late promoter (MLP) or the human cytomegalovirus (CMV)
      immediate early gene promoter. lacZ expression and GCV killing efficiency after
      TK gene transfer in several human tumor cells was evaluated in vitro. The 9L rat
      brain tumor and leptomeningeal metastases models were used to determine the
      effectiveness of adeno-TK and subsequent GCV treatment in vivo. MLP and CMV
      containing adenoviral vectors were compared. RESULTS: Gene expression and the
      killing of tumor cells were very efficient in all human tumor cell lines tested.
      The adenovirus containing the CMV promoter showed cytopathic effects in cultured
      tumor cells at high multiplicity of infections but also greater cell killing
      efficiency after TK/GCV treatment, as compared to the MLP promoter. Although both
      the MLP and CMV vectors showed a significant dose-dependent therapeutic effect,
      animals treated with recombinant adenovirus containing the CMV promoter showed
      significantly longer survival time (brain tumors) or symptom-free periods
      (leptomeningeal metastases). CONCLUSION: This study demonstrates the therapeutic
      efficiency and feasibility of the TK/GCV approach in experimental brain tumors
      and leptomeningeal metastases. It also demonstrates that the promoter driving the
      transgene in an adenoviral vector influences toxicity and efficiency of
      treatment.

PMID- 9257315
TI  - Continuous monitoring of the partial pressure of oxygen in cerebral venous blood.
AB  - OBJECTIVE: Clinical oxygen monitoring in the injured brain is somewhat difficult.
      However, ischemia is one of the major factors responsible for secondary tissue
      damage after head injury or subarachnoid hemorrhage. Therefore, the aim of the
      present study was to investigate the value of continuously monitoring the partial
      pressure of oxygen in cerebral venous blood (PcvO2) during changes in
      intracranial pressure (ICP). METHODS: In eight domestic pigs with Clark type
      probes placed in the posterior third of the superior sagittal sinus, PcvO2 was
      continuously registered while ICP was stepwise elevated by an inflatable balloon
      placed below the tentorium. Arterial blood pressure was continuously monitored,
      cerebral perfusion pressure (CPP) was calculated, and arterial partial carbon
      dioxide pressure and partial pressure of oxygen were registered intermittently.
      RESULTS: The mean intraparenchymal ICP before the start of balloon inflation was
      5 +/- 1 mm Hg, the mean CPP was 80 +/- 15 mm Hg, and the mean PcvO2 was 36 +/- 3
      mm Hg. At maximum ICP elevation, CPP decreased to 20 +/- 12 mm Hg, PcvO2
      decreased to 10 +/- 6 mm Hg, and ICP increased to 90 +/- 10 mm Hg. Strong linear
      correlations between ICP and PcvO2 and between CPP and PcvO2 were revealed, and
      mean correlation coefficients of 0.89 for ICP/PcvO2 and 0.73 for CPP/PcvO2 were
      calculated. CONCLUSION: The present study demonstrates that polarographic PcvO2
      monitoring in the superior sagittal sinus is a reliable method for the early
      detection of reduced CPP during ICP elevation. This technique is capable of
      registering the global oxygen supply and oxygen consumption of the brain. It
      seems superior to jugular venous oxymetry and is better suited for clinical use
      because of a somewhat low artifact susceptibility.

PMID- 9257316
TI  - Recovery of useful hearing after posterior fossa surgery: the role of otoacoustic
      emissions: case report.
AB  - OBJECTIVE AND IMPORTANCE: Hearing preservation has become an important issue in
      surgical procedures involving the cerebellopontine angle (CPA). Although several
      prognostic factors for hearing preservation in patients with "useful"
      preoperative hearing have been described, it is difficult to predict which
      patients have the potential for hearing preservation or recovery. Otoacoustic
      emission measurement is a new technique that allows recording of sounds produced
      by the cochlear outer hair cells as a normal byproduct of the receptor process
      and can be used to assess cochlear involvement in patients with hearing loss.
      CLINICAL PRESENTATION: We present the case of a 53-year-old patient with a
      recurrent arachnoid cyst of the CPA. She had noticed progressive severe hearing
      loss ipsilateral to the cyst that was confirmed by preoperative audiogram.
      TECHNIQUE: Otoacoustic emissions were obtained and were within normal limits on
      the involved side, suggesting that the cochlear outer hair cells were still
      intact and that the patient had the potential for hearing recovery. The CPA was
      decompressed by marsupialization of the cyst. Postoperative audiogram
      demonstrated a dramatic recovery of hearing to a normal level. CONCLUSION:
      Otoacoustic emissions clearly provide valuable information about the potential
      for hearing preservation/recovery after CPA surgery and have significant
      implications for the current neurosurgical management of these lesions.

PMID- 9257317
TI  - Middle cerebral artery stenosis caused by relatively low-dose irradiation with
      stereotactic radiosurgery for cerebral arteriovenous malformations: case report.
AB  - OBJECTIVE AND IMPORTANCE: There have been occasional reports of stenosis or
      occlusion of major cerebral arteries occurring several years after stereotactic
      radiosurgery for cerebral arteriovenous malformations. Nevertheless, little
      information is available regarding the actual irradiation dose to which the
      affected artery had been exposed. CLINICAL PRESENTATION: We present a patient
      with arteriovenous malformations who, although asymptomatic, developed remarkable
      stenosis of the middle cerebral artery trunk (M1) 3 years after gamma knife
      radiosurgery. The nidus was covered with a 50% isodose volume. A central dose of
      36 Gy was used. A gradual decrease in nidus volume had been suggested by 1- and 2
      year postradiosurgical neuroimaging examinations. Three-year postradiosurgical
      angiography revealed severe segmental stenosis of the M1, as well as remarkable
      nidus shrinkage. INTERVENTION: The actual irradiation dose delivered to the
      affected portion of the artery, as retrospectively determined using a highly
      accurate three-dimensional analysis technique, was estimated to be 5.1 to 9.8 Gy.
      CONCLUSION: This case suggests that a normal major artery, if located close to
      the target volume, may be affected by low-dose irradiation (10 Gy or even
      slightly less) delivered with radiosurgery, although a decrease in blood flow
      through the M1 because of nidus shrinkage or associated stenosis of the distal
      middle cerebral artery, as well as other unknown factors, may also contribute to
      proximal M1 stenosis.

PMID- 9257319
TI  - Nontraumatic spinal epidural hematoma: report of four cases and review of the
      literature.
AB  - OBJECTIVE AND IMPORTANCE: Spontaneous spinal epidural hematoma is a rare entity.
      We report four cases of nontraumatic spinal epidural hematomas observed from 1990
      to 1994. CLINICAL PRESENTATION: In two cases, the causes were determined to be an
      acquired coagulopathy and a vascular malformation; in the other two cases, no
      causes were detected. We reviewed 85 cases in the literature, with particular
      emphasis on the various causes detected (coagulopathy, vascular malformations,
      tumor) and the diagnostic methods used. INTERVENTION: All the patients were
      investigated by computed tomography and magnetic resonance imaging and underwent
      surgery. CONCLUSION: We considered the expression "nontraumatic epidural
      hematoma" to be less ambiguous than "spontaneous spinal epidural hematoma," which
      is the one that is usually used in the literature and corresponds to various
      definitions. In the absence of any signs suggestive of vascular malformation on
      magnetic resonance imaging, preoperative angiography is not essential and need
      not delay the surgical procedure, because the timing of the surgery, together
      with the preoperative clinical state, determines the quality of the clinical
      result.

PMID- 9257318
TI  - Lymphoma of the lumbar nerve root: case report.
AB  - BACKGROUND AND IMPORTANCE: Lymphoma deposits in the spine are typically
      extradural. However, we report the case of a 38-year-old man who had a peripheral
      T-cell lymphoma with both intra- and extradural involvement. CLINICAL
      PRESENTATION: The patient presented with a 3-month history of right hip and thigh
      pain. Computed tomography and magnetic resonance imaging revealed features
      indistinguishable from those of a benign neurofibroma, except for a small area of
      T2-weighted signal abnormality in the third lumbar vertebral body. INTERVENTION:
      A solitary lesion of the right third lumbar root with normal surrounding bone and
      soft tissue was excised at surgery. At immunohistopathological evaluation, a
      diagnosis was made of peripheral lymphoma. Postoperative evaluation did not
      reveal lymphoma in the cerebrospinal fluid, abdomen, chest, blood, or bone
      marrow. This case illustrates that lymphomas can grow in patterns
      indistinguishable from a tumor of a nerve root. Therefore, other treatment
      modalities would have been considered had the diagnosis of lymphoma been made
      preoperatively. CONCLUSION: Involvement of a solitary nerve root by lymphoma,
      although rare, should be suspected in all cases of nerve root neurofibroma, and
      magnetic resonance imaging should be performed. Even minor signal abnormalities
      in adjoining vertebrae signal the possibility of malignancy. Percutaneous biopsy
      of suspicious bony lesions and systemic evaluation can demonstrate other sites of
      involvement, enabling the confirmation of the diagnosis and appropriate treatment
      without recourse to surgery.

PMID- 9257321
TI  - Syringostomy using myringostomy tube: technical note.
AB  - OBJECTIVE: We describe the concept of a new syringostomy technique. METHODS: The
      technique includes the insertion of a myringostomy tube through a small myelotomy
      at the level of maximum enlargement of the syrinx. The inner diameter of the
      myringostomy tube is 1.14 mm. RESULTS: This technique reduces the potential risks
      that are associated with other techniques that use bulky silastic catheters that
      are left inside the spinal cord. CONCLUSION: We think that this technique is the
      least invasive of all similar techniques and that, in terms of drainage, the
      myringostomy tube is as efficient as commonly used silastic catheters.

PMID- 9257320
TI  - Corpus callosal changes associated with hydrocephalus: a report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Focal or diffuse corpus callosal changes can occur in
      patients with active hydrocephalus who undergo shunting procedures. The neural
      compression caused by active hydrocephalus and the conditions that follow
      ventricular shunting may contribute to the development of these changes. CLINICAL
      PRESENTATION: Two patients who underwent successful shunting for hydrocephalus
      subsequently developed thickening and diffuse signal changes in the corpus
      callosum, which were revealed by magnetic resonance imaging. The abnormal signal
      intensity extended laterally and linearly along the callosal fiber tracts and was
      not associated with mass effect. These changes persisted despite clinical
      improvement after the shunts were implanted. INTERVENTION: Detailed
      neuropsychological testing showed no evidence of residual cognitive impairment or
      any interruption of the interhemispheric transfer of information. It has been
      proposed that the impingement of the corpus callosum by the rigid falx may
      contribute to symptomatic hydrocephalus. Impingement may cause partial
      hemispheric disconnection, resulting from callosal axonal dysfunction. Our
      patients showed radiographic evidence of dramatic changes within the corpus
      callosum after ventricular shunting, consistent with a transcallosal
      demyelinating process. Patients demonstrated neither clinical nor
      neuropsychological evidence of callosal disconnection, even though the callosal
      changes persisted. In these two patients, it is reasonable to assume that the
      relative sparing of the splenium accounts for the lack of neuropsychological
      deficits. CONCLUSION: Based on our findings, conservative management, rather than
      a stereotactic biopsy or other forms of intervention, seems reasonable when these
      characteristic changes of the callosum are noted by magnetic resonance imaging
      after a shunt for hydrocephalus has been implanted in the patient.

PMID- 9257322
TI  - Split cannula method for accurate placement of an electrode for deep brain
      stimulation: technical note.
AB  - OBJECTIVE: We describe a "split cannula method" for accurate placement of a deep
      brain stimulation electrode. This method eliminates the risk of displacement of
      the electrode when withdrawing the outer guide cannula. METHOD: A separate short
      guide cannula is covered over the distal part of a long cannula for
      microrecording or macrostimulation. After confirmation of the stimulation point,
      the short cannula is fixed with an accessory-holding device and the long cannula
      is pulled out. The electrode for deep brain stimulation is inserted through the
      short cannula. Because this cannula is much shorter than the electrode, securing
      the stimulation electrode at any withdrawal stage of the outer guide cannula is
      always possible. RESULTS AND CONCLUSION: With this simple method, we experienced
      no displacement of the stimulation point during stereotactic insertion of a deep
      brain stimulation electrode. This method can be easily adapted to any
      stereotactic frame.

PMID- 9257323
TI  - Functional magnetic resonance imaging: a potential tool for the evaluation of
      spinal cord stimulation: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: The management of chronic pain of spinal origin
      continues to represent a challenge for neurosurgeons. Spinal cord stimulation for
      chronic intractable pain is an effective therapy in approximately 50% of
      patients. The present study uses a novel imaging approach, functional magnetic
      resonance imaging (fMRI), to examine the central effects of spinal cord
      stimulation. CLINICAL PRESENTATION: Three patients, each with a chronic history
      of intractable pain, were treated at the Toronto Hospital with a trial of dorsal
      column stimulation (DCS). For all patients, significant improvement in pain
      symptoms was achieved with DCS. INTERVENTION: fMRI on a 1.5-T conventional
      magnetic resonance system was used to study the effects of DCS in these patients.
      Images were collected while the stimulator was activated and deactivated.
      CONCLUSION: This report is the first to describe the cerebral effects of
      exogenous spinal cord stimulation with fMRI. fMRI allows for the objective
      examination of the effects of DCS and may provide an objective means of
      evaluating the efficacy of DCS as a therapy for intractable pain of spinal
      origin.

PMID- 9257324
TI  - Relief of glossopharyngeal neuralgia by ketamine-induced N-methyl-aspartate
      receptor blockade.
AB  - OBJECTIVE: We examined whether ketamine, which is a noncompetitive blocker of N
      methyl-D-aspartate (NMDA) receptors, had the ability to relieve glossopharyngeal
      neuralgia. A tentative hypothesis is that glossopharyngeal neuralgia involves
      hyperactivity in the central nociceptive neurons and that the development of this
      hyperactivity is dependent on activation of NMDA receptors. CLINICAL
      PRESENTATION: The pain syndrome of this 56-year-old woman had lasted for
      approximately 7 years and was localized to the posterior pharynx, tonsillar
      region, and base of the tongue, with radiation to the left deep ear structures.
      Pain was provoked by swallowing. INTERVENTION: It was first determined in a
      double-blind experiment that intravenous ketamine markedly reduced pain. The
      optimal oral dose (60 mg administered six times/d) was observed in an open dose
      escalating trial. In an N of 1 trial, the patient received double blindly either
      oral ketamine (60 mg administered six times/d) or placebo during 10 2-day
      periods. Ketamine caused marked pain relief, as shown by statistically
      significant pain relief and reduction of pain intensity. Pain caused by
      swallowing also was reduced by ketamine. Pain relief was associated with some
      side effects; however, the treatment was well tolerated by the patient.
      CONCLUSION: This case report shows that ketamine-induced NMDA receptor blockade
      significantly relieved glossopharyngeal neuralgia in this patient. Therefore,
      NMDA receptors may play a significant role in the pathogenesis of the pain
      syndrome described.

PMID- 9257325
TI  - PET-pharmacokinetics of 18F-octreotide: a comparison with 67Ga-DFO- and 86Y-DTPA
      octreotide.
AB  - The quantitative uptake kinetics of (2-[18F]fluoropropionyl-(D)phe1)-octreotide
      (I), a somatostatin (SRIF) receptor-specific tracer, was measured by PET.
      Conventional organ biodistribution and in vivo stabilities of the tracer as well
      as in vivo displacement and SRIF receptor blocking were determined. The 18F
      fluorinated octreotide was compared with ([67Ga]-DFO-B-succinyl-(D)phe1)
      octreotide (II) and ([86Y]-DTPA-(D)phe1)-octreotide (III). Initially, 2-10 MBq of
      the labeled tracers were injected into male Lewis rats bearing an exocrine
      pancreatic islet cell tumor. PET measurements were performed dynamically between
      0 and 120 min postinjection. Organ distributions were determined 5, 15, 30, 60,
      and 120 min postinjection. The extent of metabolic degradation was analyzed in
      serial blood and urine samples as well as in homogenized samples of tumor, liver,
      and kidney. The uptake of (I) by the tumor was rapid (maximum accumulation at 1-2
      min postinjection) and high (about 0.5 +/- 0.2% ID/g), followed by a fast and
      continuous release with koff = 10 +/- 2. 10(-5) s-1. The tracer was found to
      remain intact in vivo up to 120 min postinjection. Specific binding of (I) to
      SRIF receptors in the adrenals, the pancreas, and the pituitary gland was
      demonstrated in vivo by pretreatment and displacement experiments. Compound (II)
      also showed a fast uptake by the tumor. Its tumor residence half-life was longer
      (koff = 3.0 +/- 0.5 . 10(-5) s-1). Compound (II) was also predominantly excreted
      intact. One hour postinjection, the remaining activity in the blood pool was
      found to be bound to serum proteins. Early uptake kinetics for compound (III)
      were also rapid but reached only half the tumor uptake of (II). Compared to (I),
      the release of 86Y-activity from the tumor was slower (koff = 3.1 +/- 1.3 . 10(
      5) s-1). Compared to (II), compound (III) was considerably less stable in vivo.
      The main critical organs for (II) and (III) are kidneys and bones, whereas (I) is
      predominantly accumulated in the liver. The in vivo behavior of (I) closely
      resembles 14C-labeled octreotide. Thus, 18F-labeled octreotide may be of interest
      in the quantitation and investigation of in vivo properties of somatostatin
      receptors by PET. However, the short residence of (2-[18F]fluoropropionyl
      (D)phe1)-octreotide in tumors and its hepatobiliary excretion may complicate the
      interpretation of abdominal tumors.

PMID- 9257326
TI  - 11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo
      studies.
AB  - Frozen-section autoradiography in rat brain sections as well as in vivo positron
      emission tomography (PET) studies in monkey brain were used for the determination
      of binding characteristics of O-[methyl-11C]harmine in an attempt to validate
      this ligand for the assessment of monoamine oxidase A (MAO-A). In frozen
      sections, the binding of [11C]harmine showed an apparent KD of the binding of 2
      nM. The specific binding was inhibited by nanomolar concentrations of clorgyline,
      esuprone, brofaromine, and Ro 41-1049. The in vivo kinetic pattern in the monkey
      brain indicated a significant trapping, which was inhibited by pretreatment with
      clorgyline, moclobemide, or harmine. Different approaches for a quantitative
      determination of MAO-A enzyme binding were attempted and demonstrated an IC50
      dose of harmine in the range of 0.05-0.1 mg/kg. The studies give strong
      indications for the validity of [11C]harmine as an in vivo tracer for the
      assessment of MAO-A enzyme binding in the brain.

PMID- 9257327
TI  - Preparation of 8-[3-(4-fluorobenzoyl)-propyl]-1-(4-[123I] iodobenzoyl)-1,3,8
      triazaspiro[4,5]decan-4-one: a novel selective serotonin 5-HT2 receptor agent.
AB  - In our attempt to develop radioiodinated serotonin 5-HT2 receptor imaging agents
      for routine clinical application with single photon emission computed tomography
      (SPECT), the [123I]iodinated compound 8-[3-(4-fluorobenzoyl)-propyl]1-(4
      [123I]iodobenzoyl)- 1,3,8-triazaspiro[4,5]decan-4-one [123I]IBSP was prepared via
      no-carrier-added Cu(I)-assisted radio-iododebromination in acetic acid, followed
      by purification by means of reversed-phase HPLC in 70-90% radiochemical yield and
      high specific activities at a total synthesis time of 50 min. Moreover, [123I]
      IBSP is stable up to 48 h in aqueous solution at room temperature and revealed
      appropriate lipophilicity (logP = 2.8) for good diffusion through the blood-brain
      barrier. Competitive binding studies on rat brain membranes using [3H]ketanserin,
      [3H]SCH23390, and [3H]spiperone as radioligands (for 5-HT2, D1 and D2 receptors,
      respectively) indicated that IBSP has high affinity and selectivity for the
      serotonin 5-HT2 receptor (Ki = 7.0 nM) over the dopamine D2 (Ki = 153 nM) and D1
      receptors (Ki = 265 nM). These data suggest that [123I]-IBSP may be a promising
      compound for studying 5-HT2 receptors with SPECT.

PMID- 9257328
TI  - Radioiodinated methylene blue for melanoma targeting: chemical characterisation
      and tumour selectivity of labelled components.
AB  - Radioiodinated methylene blue contains a mixture of components showing selective
      uptake in human pigmented melanoma, and it has potential for imaging and therapy.
      Nuclear magnetic resonance and mass spectroscopic studies show that the majority
      of the radioactivity (85%) is in the form of monoiodinated methylene blue, 4-iodo
      3-methylamino-7-dimethylaminophenaza thionium chloride. The amino group ortho-to
      iodine has become demethylated to a mono-methylamino group. The remainder (15%)
      of the mixture is the doubly labelled 4,5-diiodo-3,7-bis(methylamino)
      phenazathionium chloride. The separated components show similar tumour
      selectivity in athymic mice bearing human pigmented melanomas.

PMID- 9257329
TI  - Radiation dosimetry of [18F] (N-methyl)benperidol as determined by whole-body PET
      imaging of primates.
AB  - Radiation absorbed doses due to IV administration of [18F](N-methyl) benperidol
      ([18F]NMB) were estimated by whole-body PET imaging of nonhuman primates. Time
      activity curves were obtained for nine compartments (striatum, eyes, heart,
      lungs, liver, gallbladder, intestines, kidneys, bladder) by using dynamic PET
      scans of three different baboons given the radiotracer. These time-activity
      curves were used to calculate the residence times of radioactivity in these
      tissues. Human absorbed dose estimates were calculated using the updated MIRDOSE
      3 S values and assuming the same biodistribution. Based on an average of three
      studies, the critical organs were the lower large intestine, gallbladder, and
      liver, receiving doses of 585, 281, and 210 mrad/mCi, respectively. The brain
      received a dose of 13 mrad/mCi; other organs received doses between 32-77
      mrad/mCi. These results indicate that up to 8.5 mCi of [18F]NMB can be safely
      administered to human subjects for PET studies of D2 receptor binding.

PMID- 9257330
TI  - Positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) in
      patients with metastatic hormone-refractory prostatic adenocarcinoma.
AB  - The discovery of neuroendocrine differentiation in hormone-refractory prostatic
      adenocarcinoma has opened a potentially new therapeutic approach in this group of
      patients with a poor prognosis and few effective therapy modalities. Based on
      previous findings of increased uptake of 11C-5-hydroxytryptophan (11C-5-HTP) in
      neuroendocrine tumours using the PET technique, this tracer was applied in the
      study of 10 patients with metastatic hormone-refractory prostatic adenocarcinoma.
      In three patients, the study was repeated after treatment. An increased uptake of
      11C-5-HTP was observed in all investigated skeletal lesions, although the
      magnitude of the uptake was moderate. The difference between the standard uptake
      values (SUV) in normal bone and metastatic lesions was significant (p < 0.001). A
      kinetic analysis of the uptake of 11C-5-HTP demonstrates an increase during the
      first minutes followed by a wash-out and a stabilization of the tissue/blood
      ratio at about 2. The Patlak plots demonstrated a gradual increase in the
      transport rate during the first 20 to 30 min, after which a constant level was
      observed. The SUV varied between patients and between lesions over time and
      treatment. The uptake of 11C-5-HTP discriminates metastatic lesions from normal
      bone and may thus aid in the diagnosis and, potentially, in treatment monitoring
      of metastatic hormone-refractory prostatic adenocarcinoma. Uptake kinetics are
      characterized by a wash-out and cannot alone be used as proof of neuroendocrine
      differentiation in hormone-refractory prostatic adenocarcinoma.

PMID- 9257331
TI  - Disposition of intravenous 123iodopentamidine in man.
AB  - This study compared the disposition of the radiopharmaceutical
      [123I]iodopentamidine with that of pentamidine after intravenous infusion by
      measuring plasma concentrations of each using scintilation counting and high
      performance liquid chromatography (HPLC), respectively. There was rapid hepatic
      uptake and biliary excretion of the 123I label. Distribution kinetics of the 123I
      label were similar to those of pentamidine, but its elimination half-life (41 +/-
      27 h) was longer than that of pentamidine measured by HPLC (11 +/- 8 h).
      [123I]iodopentamidine distribution reflects that of pentamidine, but elimination
      of the radiopharmaceutical appears slower.

PMID- 9257332
TI  - Synthesis and evaluation of [18F] labeled benzamides: high affinity sigma
      receptor ligands for PET imaging.
AB  - We have synthesized and characterized four new fluorinated halobenzamides as
      sigma receptor ligands for use with positron emission tomography (PET). All the
      compounds were found to have high sigma-1 affinities (Ki = 0.38-0.98 nM), and the
      4-fluoro-substituted benzamides were found to be more potent sigma-2 ligands (Ki
      = 3.77-4.02 nM) than their corresponding 2-fluoro analogs (Ki = 20.3-22.8 nM).
      The [18F] radiochemical syntheses of two of the analogs gave overall yields
      between 3-10% (EOS), radiochemical purities > 99%, and specific activities
      between 800-1200 Ci/mmol (29.6-44.4 TBq/mmol). Rat biodistribution and blocking
      experiments were performed with 2-[18F](N-fluorobenzylpiperidin-4yl)-4
      iodobenzamide, the analog with the best Ki value for sigma-1 sites (0.38 nM).
      Results of these experiments demonstrate specific uptake of the compound in
      tissues believed to contain sigma receptors, such as lungs, kidneys, heart,
      brain, and spleen and indicate its potential as a candidate for use in PET
      imaging of tissues containing these receptors.

PMID- 9257333
TI  - Analysis of blood clearance and labeled metabolites for the estrogen receptor
      tracer [F-18]-16 alpha-fluoroestradiol (FES).
AB  - [F-18] 16 alpha-Fluoroestradiol (FES) has been shown to be a tracer of estrogen
      receptor content in breast tumors; however, quantitative analysis of FES images
      is complicated by the rapid metabolism of the tracer in vivo. To optimize FES PET
      imaging studies and to provide an input function for the quantitative analysis of
      the tracer FES uptake in breast tumors, we studied the clearance and metabolism
      of FES in 15 breast cancer patients. FES clearance, protein binding, and
      metabolite production and limited assays to determine the identity of labeled
      metabolites were performed. These studies show that FES was rapidly cleared from
      the blood and metabolized; at 20 min only 20% of the circulating radioactivity
      was unmetabolized FES, and much of this was protein bound. The detectable
      metabolites in either blood or urine are conjugation products, largely the
      glucuronide and the sulfate of FES, and these are excreted through the kidneys at
      a rate comparable to their introduction into the circulation. After 20 min
      postinjection the blood levels of radioactivity remain fairly constant. Our
      results, the first report on human metabolites, are in close agreement with
      previous animal studies of FES metabolism. These studies show that because FES
      clearance is rapid and metabolite background is nearly constant, imaging starting
      at 20 to 30 min after injection may provide good visualization of estrogen
      containing tissues. Labeled metabolites need to be accounted for in quantifying
      FES uptake.

PMID- 9257334
TI  - Uptake of 169Yb complexes in normal and tumour cells: influence of ligand and
      metabolic cell activity and stability of cellular association.
AB  - For better understanding of the accumulation of trivalent radiometal tracers in
      tumours, studies of uptake of different 169Yb complexes into cultured normal
      (V79/4) and tumour (KTCTL-2) cells were performed. Cellular uptake of 169Yb3+ is
      dependent on both the metabolic activity of the cells and the nature of the
      ligand used. Uptake of 169Yb3+ from the citrate complex is an active cellular
      transport process but not tumour-specific. The 169Yb-aminopolycarboxylic acid
      complexes are taken up via a different, unknown mechanism, and in higher amounts
      by the tumour cells than by the V79/4 cell line, but the general features of
      uptake were principally the same with the normal and the tumour cells. Uptake of
      the complexes studied leads to a stable association of cellular components, which
      is a good premise for the therapeutic use of trivalent radiometals.

PMID- 9257335
TI  - In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and
      electronic autoradiographic study.
AB  - To further validate its use in positron emission tomography (PET), we studied the
      binding of [18F]altanserin, a specific 5HT2 radioligand, in the rat brain using
      in vivo autoradiography. Distribution of [18F]altanserin binding was comparable
      to the in vitro mapping of 5HT2 receptors reported in the literature. Selective
      displacers were used to test the reversibility and the selectivity of this
      radioligand. Specific binding of [18F]altanserin in the rat frontal cortex was
      quantified by direct counting with an electronic imaging system and by
      quantification on digitalized autoradiograms. Close results of about 30 pmol/g
      were obtained with both methods. Our data confirmed that [18F]altanserin is a
      valid tracer for 5HT2 receptors binding studies.

PMID- 9257336
TI  - The use of electronic autoradiography in radiopharmacy.
AB  - The use of Microchannel Plate Analysers (Instant Imager, Canberra Packard), the
      so called Electronic Autoradiography, in Radiopharmacy is described. The system
      can be used for quality control of radiopharmaceuticals as well as for scientific
      research purposes. Quantitative analysis of 2-dimensional radioactive samples of
      all radionuclides used in Nuclear Medicine (especially 99mTc) can be performed in
      a very short time with little effort. Advantages and limitations for
      radiopharmaceutical work are described.

PMID- 9257337
TI  - Resting behaviour, ecology and genetics of malaria vectors in large scale
      agricultural areas of Western Kenya.
AB  - In Kenya indoor and outdoor resting densities of Anopheles arabiensis and
      Anopheles funestus at the Ahero rice irrigation scheme, and Anopheles gambiae
      s.s., An. arabiensis and An. funestus at the Miwani sugar belt were assessed for
      13 months by pyrethrum spray collections in houses and granaries. The vector's
      house leaving behaviour was evaluated with exit traps and it was noted that early
      exophily (i.e., deliberate) was not detected in any of the vectors. Assortative
      indoor/outdoor resting behaviour was studied by a capture-mark-release-recapture
      method and showed that in An. arabiensis both indoor and outdoor resting traits
      were present in the same individuals. Samples of half-gravid female An. gambiae
      s.l. were chromosomally identified either as Anopheles gambiae s.s. or An.
      arabiensis and in a subsample chromosomal inversions were read. Anopheles gambiae
      s.s. and An. arabiensis had the 2Rb inversion but in addition the 2La inversion
      was found in An. gambiae s.s. and this is an indication of low chromosomal
      variation. At Ahero An. arabiensis was most abundant when the rice crop was
      immature and An. funestus when the crop was mature. This succession of vectors
      facilitated the transmission of malaria throughout the year. At Miwani, An.
      gambiae s.l. population peaked during the long rains but the proportion of An.
      arabiensis was highest during the dry season. The indoor resting density of males
      of the three vector species was less than half of the females.

PMID- 9257338
TI  - A new species of Culicoides (Diptera, Ceratopogonidae) from southern Italy.
AB  - Culicoides paolae, a new species of Ceratopogonidae from southern Italy, and
      which superficially resembles an important vector of animal diseases, is
      described in both sexes. Its potential veterinary importance is discussed
      briefly.

PMID- 9257339
TI  - Contribution to the knowledge of helminthofauna of wild mammals of Somalia.
AB  - Within a survey of parasitic infections in wild mammals of Somalia, during the
      first semester of 1983 and the second of 1984, endoparasites were collected from
      11 host species: Gazella soemmeringi, Gazella spekei, Madoqua saltiana,
      Phacochoerus aethiopicus, Xerus rutilus, Lepus sp., Genetta genetta, Herpestes
      (Galerella) sanguineus, Felis sylvestris libyca, Felis caracal, Canis mesomelas.
      A total of 22 species of helminths (20 nematode and 2 metacestode species) were
      identified. Lepus sp. is a new host for Heteroxinema (P.) proboscidiphora and
      Herpestes sanguineus for Oxinema sp. Teladorsagia hamata had not been previously
      reported in G. spekei; the genital cone and the corresponding supporting
      apparatus of this nematode are described. Two metacestodes were collected from
      the mesenteric membranes of a P. aethiopicus. The shape, number and length of
      their rostellar hooks, the size of the larvocysts, the occurrence of
      pseudostrobilum, are similar to those of the Taenia regis metacestode: but the
      size and shape of the hooks of the Somalian warthog larvocysts are slightly
      different and they have not been recovered from the musculature as previously
      reported in the intermediate hosts of T. regis.

PMID- 9257341
TI  - Some morphological aspects of the mouthparts of Italian blood-sucking muscids
      (Diptera, Stomoxyinae).
AB  - Scanning electron microscopy (SEM) observations on the mouthparts of four species
      of blood-sucking muscid symbovine flies (Stomoxys calcitrans Linnaeus, Haematobia
      irritans Linnaeus, H. titillans Bezzi, and Haematobosca stimulans Meigen) are
      described. The morphology of some structures (haustellum, prestomal teeth and
      petiolate blades) is compared in order to draw attention to those features
      involved in the feeding process on the hosts.

PMID- 9257340
TI  - A study on the distribution of Bothriocephalus andresi (Cestoda, Pseudophyllidea)
      in Citharus linguatula.
AB  - The distribution of Bothriocephalus andresi (Porta, 1911) in a population of
      Citharus linguatula (L.) caught off the Tuscan coasts was studied for one year.
      The negative binomial model proved useful for analysing the distribution of the
      parasite (B. andresi) in the host population. The ability of the parasite to
      adjust not only to its own environment but also to that of its host was clear, as
      it may be evinced from the greater amount of eggs and, hence, of larvae noticed
      in the period when there was abundance of plankton (high number of intermediate
      hosts). The balance achieved between host and parasite populations was also
      evident, and the modulation of the intensity of the infestation was such that it
      may be imputed to a greater immune response in the host.

PMID- 9257342
TI  - Trypanosomes, tsetse and trypanotolerance: coevolution in tropical Africa.
AB  - Trypanotolerance reaches varying degrees of stability in wild and domestic
      animals according to their co-evolutionary contacts with tsetse flies and
      trypanosomes. In this context, various mechanisms developed by wild and domestic
      Bovidae to cope with tsetse and trypanosome challenge are discussed.

PMID- 9257343
TI  - Distribution and density of house dust mites Dermatophagoides spp.
      (Acarina:Pyroglypidae) in the mattresses of two areas of Rome, Italy.
AB  - The distribution of Dermatophagoides farinae and D. pteronyssinus in two groups
      of houses in Rome was investigated by means of weekly sampling of dust on
      mattresses during the period of high mite density (May-July, 1994). All
      mattresses were infested; overall 4,179 live and dead mites were collected. In
      the two examined areas, a difference in species distribution was observed. D
      farinae was always the prevalent species, it was 94.7% in area A and 64.1% in
      area B; only in houses 9 and 10 D. pteronyssinus was the most abundant species
      (71.4% and 45.8%). Housekeeping practices were investigated by interviewing the
      tenants and relative humidily and indoor/outdoor temperature were measured during
      each weekly sampling. A correlation analysis revealed a significant relationship
      between housekeeping practices and mite density (r = 0.83). The poorest
      housekeeping practices produced the heaviest mite infestation, while good ones
      were associated with low densities.

PMID- 9257345
TI  - Epitope mapping on the ookinete surface antigen Pbs21 of Plasmodium berghei:
      identification of the site of binding of transmission-blocking monoclonal
      antibody 13.1.
AB  - The ookinete surface protein of Plasmodium berghei Pbs21 belongs to a class of
      sexual stage antigens able to induce in the vertebrate host a transmission
      blocking immune response. The effectors of this transmission-blocking immunity
      are antibody molecules directed against particular protein epitopes. The anti
      Pbs21 monoclonal antibody 13.1 is known to bind a linear stretch of amino acids
      within the primary sequence of Pbs21 and to efficiently block the development of
      P. berghei in the mosquito gut. To map the 13.1 epitope along the amino acid
      sequence of Pbs21 we assayed the ability of 13.1 antibody to recognize, in
      Western blot, a series of Pbs21 deletion mutants as well as the ability of
      synthetic peptides to inhibit 13.1 binding to full length Pbs21. The epitope was
      identified within the second EGF-like domain of the Pbs21 molecule.

PMID- 9257344
TI  - A rapid method for restriction analysis of large plasmids from enteric pathogens.
AB  - A modified version of the method of Kado and Liu (J Bacteriol 1981, 145: 1365)
      has been developed for rapid detection and direct cleavage analysis of large
      plasmids from Vibrio cholerae and other enteric pathogens.

PMID- 9257346
TI  - Antelopes (Bovidae) kept in European zoological gardens as intermediate hosts of
      Sarcocystis species.
AB  - Four different forms of sarcocysts from the zoo-kept antelopes Addax
      nasomaculatus. Antilope cervicapra, Taurotragus oryx and Boselaphus tragocamelus
      (Bovidae) were investigated by light and transmission electron microscopy, in
      special consideration of the cyst wall. The sarcocysts found in Addax (born in a
      zoo) were not distinguishable from Sarcocystis medusiformis of Australasian sheep
      by their morphology and would be the first indication for the occurrence of this
      species in Europe. Sarcocysts from Antilope (born in a zoo) resembled the
      tenella/capracanis type of sheep/goats and were, therefore, designated as
      Sarcocystis sp. (? cf. capracanis) in this paper. Sarcocysts from Taurotragus
      were similar to a zoonotic species of cattle and hence provisionally designated
      as S. sp. (? cf. hominis). A sarcocyst form with hair-like villar protrusions of
      the cyst wall was found in Taurotragus. Boselaphus and Antilope and compared with
      a common species of cattle: S (? cf. cruzi).

PMID- 9257347
TI  - Contribution to the knowledge of Ixodidae ticks of wild mammals of Somalia.
AB  - This study was based on material collected in 1983-1984 from wild mammals of the
      Middle Scebeli. Low Scebeli and Bay Regions of Somalia. A total of 292 specimens
      (156 males, 65 females, 70 nymphase, 1 larva) from 13 host species were examined.
      The following species of ixodidae were identified. Amblyomma variegatum
      (Fabricius, 1794); Haemaphysalis calcarata Neumann, 1902; Haemaphysalis spinulosa
      Neumann, 1906; Rhipicephalus armatus Pocock, 1900; Rhipicephalus pravus Donitz,
      1910; Rhipicephalus pulchellus Gerastcker, 1873; Rhipicephalus sanguineus
      (Latreille, 1806); Rhipicephalus simus Koch, 1844. H. spinulosa was found
      throughout the majority of host species (10 mammalian species).

PMID- 9257348
TI  - Synchronized Plasmodium yoelii yoelii: pattern of gametocyte production,
      sequestration and infectivity.
AB  - The chronobiology of the gametocytes of P. yoelii was studied in Percoll-glucose
      synchronized infection in the mouse. The gametocyte developmental cycle consisted
      of 4 successive stages: stage 0 maturation took 27 hours from merozoite invasion,
      stage 0 to stage 1 lasted 6 hours, stage I to stage II and stage II to stage III
      lasted 3 hours each. Stage 0 gametocytes were found to sequester in small
      peripheral capillaries, and the number of oocysts in mosquitoes was related to
      the number of stage 0 gametocytes ingested.

PMID- 9257349
TI  - Cutaneous leishmaniasis in Libya: epidemiological survey in Al-Badarna.
AB  - One hundred fifty-one cutaneous leishmaniasis (CL) cases were recorded during the
      period from October 1991 to September 1992 from Al-Badarna in Jabal Nafusa, an
      endemic area of CL in Libya. The infection was clinically suspected and confirmed
      by the demonstration of Leishmania on smears from lesion biopsies. The age
      distribution of cases showed that the age group 1-10 yrs was the most affected,
      indicating that the endemic status of CL in Al-Badarna is not a new occurrence.

PMID- 9257350
TI  - Parasites in Italian sea turtles. I. The leatherback turtle Dermochelys coriacea
      (Linnaeus, 1766).
AB  - Three species of trematodes (Digenea) were collected from a leatherback turtle
      (Dermochelys coriacea) stranded on the coast of Lampedusa (Sicily Channel,
      Mediterranean Sea, Italy). One, Enodiotrema carettae, was found in the liver and
      two, Enodiotrema instar and Pyelosomum renicapite, in the intestine. E. carettae
      and E. instar are new host findings, E. carettae is a geographic novelty as well.
      A description of E. instar, previously reported and described by Looss (1902), is
      included.

PMID- 9257351
TI  - A journey from blame to empathy in a family assessment of a mother and her sons.
AB  - Psychotherapists undertaking conjoint family treatment often feel stymied by the
      intensity and refractoriness of blaming among family members. Therapists feel
      drawn in as judges and referees, roles which do not seem to offer a possibility
      for constructive therapeutic activity. Embedded within the blameful exchanges,
      however, may be occasional moments of reflection by one or more members.
      Attending to these thoughtful experiences, rather than focusing on the angry
      exchange affords the therapist the opportunity of depending understanding and
      empathy among the family members. The family session described herein illustrates
      this evolution from blame to empathy.

PMID- 9257352
TI  - Configurational analysis for case formulation.
AB  - Diagnosis by DSM-IV is seldom sufficient to the task of planning and conducting
      treatment by psychotherapy. Formulation is vital for the task. I have developed a
      formulation approach called configurational analysis, and usually employ this
      tool in my work with individual adult cases. However, in this paper, I have also
      applied it to an evaluation session of a small, three-person family.

PMID- 9257353
TI  - Integrative psychobiological approach to psychiatric assessment and treatment.
AB  - A Developmental approach to integrative psychobiology provides a flexible
      framework for both clinical assessment and treatment planning. Assessment of
      seven dimensions of personality using the Temperament and Character Inventory
      (TCI) allows for comprehensive description of individual differences in feelings,
      thoughts, and actions. Four temperament factors that are stable throughout life
      can be decomposed in terms of their underlying genetic structure. Character
      factors that mature in response to social learning can be decomposed in terms of
      the components that unfold in a stepwise fashion from infancy through adulthood.
      Pharmacotherapy and psychotherapy can be systematically matched to the
      personality structure and stage of character development of each individual. This
      provides comprehensive paradigm that integrates psychodynamic, cognitive
      behavioral, interpersonal, and neurobiological insights into case formulation.
      Use of the TCI in clinical assessment and treatment planning was illustrated by a
      case independently assessed by Mardi Horowitz using another approach.

PMID- 9257354
TI  - Vulnerability to schizophrenia and psychotherapeutic treatment of schizophrenic
      patients: towards an integrated view.
AB  - My approach to schizophrenia and its treatment has evolved gradually over my
      forty-year experience as a family researcher and a psychotherapist to
      schizophrenic patients. I am convinced that we must maintain a comprehensive
      view, both with regard to the factors contributing to vulnerability to
      schizophrenia and concerning our treatment activities, and not limit our views
      with studies focusing on restricted spheres of interest. I will present some
      viewpoints concerning both the biological and the psychosocial factors
      contributing to the vulnerability to schizophrenia. My aim is to indicate that
      these factors are heterogeneous and differently weighted in different cases.
      However, an integrated notion of the pathways leading to schizophrenia can be
      proposed. I will also review the therapeutic approach-the need-adapted treatment
      of schizophrenic psychoses-which I and my coworkers have developed in Finland and
      which, in many respects, is related to these views.

PMID- 9257355
TI  - The concept of affect logic: an integrative psycho-socio-biological approach to
      understanding and treatment of schizophrenia.
AB  - In this article, the psycho-socio-biologically integrative concept of affect
      logic, and its relevance for a comprehensive understanding and therapy of
      schizophrenia, is briefly presented. This concept has been developed by the
      author over the past 20 years, on the basis of the literature, of clinical
      experience and his own research into long-term evolution, rehabilitation, effects
      of milieu-therapy, and nonlinear evolutionary dynamics of the illness. It
      postulates, basically, that fundamental affective states (or emotions, feelings,
      moods) are continuously and inseparably linked to all cognitive functioning (or
      "thinking" and "logic" in a broad sense), and that affects have essential
      organizing and integrating effects on cognition. Schizophrenia is understood as
      an altered mode of affective-cognitive interaction based, possibly, on disturbed
      (loosened) affective-cognitive connections. This hypothesis leads to: 1) an
      integrative psycho-socio-biological model of long-term evolution of the illness;
      2) a new understanding of psychopathological core phenomena such as ambivalence,
      incoherence, and emotional flattening; 3) an innovative therapeutic approach
      based on an emotion-relaxing milieu and style of care; and 4) the hypothesis that
      schizophrenia could basically be an affective (and not a cognitive) disease, of
      another kind than mania or melancholia, however.

PMID- 9257356
TI  - Biparental psychopathology and borderline personality disorder.
AB  - The pathology of parents is thought to be associated with the emergence of
      Borderline Personality Disorder (BPD) among offspring by both genetic and
      environmental pathways (Links and Blum 1990). In an effort toward clearer
      delineation, not only reliable diagnoses of patients, but also direct study of
      families, are recommended (Gunderson 1990; Gunderson and Zanarini 1989; Links and
      Blum 1990; Ogata et al. 1990; Zanarini et al. 1990). With this in mind, we
      conducted a pilot, retrospective study of parental psychiatric status,
      developmental events, and family climate during the developmental years of 30
      young women hospitalized for BPD, to be reported here. In studying these three
      dimensions of family life, we hoped to shed light on environmental underpinings
      (Gunderson 1990; Gunderson and Zanarini 1989; Links 1992; Rutter and Quinton
      1984). Even though our cohort is small and select, and the data on a comparison
      group not yet available, our research approach holds promise of yielding fresh
      insights.

PMID- 9257357
TI  - Treatment team in conflict: the wishes for and risks of consensus.
AB  - This article explores the clinical, systemic, and interpersonal dynamics of
      conflict between therapists on a treatment team. It considers treatment
      implications in regard to how therapists handle conflicts with one another, and
      focuses attention on the pressure they experience to resolve differences and
      reach consensus. Specifically, the author suggests that the therapist's ability
      to tolerate a lack of consensus, and to understand and accept conflicting
      perspectives with respect to a given patient, can help that patient begin to
      tolerate and integrate his or her own ambivalent feelings. Such integrative
      efforts may enable the patient to eventually deal with conflicting affects more
      directly within a single therapeutic relationship.

PMID- 9257358
TI  - Cosinor analysis of circadian peak expiratory flow variability in normal
      subjects, passive smokers, heavy smokers, patients with chronic obstructive
      pulmonary disease and patients with interstitial lung disease.
AB  - Peak expiratory flow (PEF) presents a circadian rhythm with a maximum in the
      afternoon, and a significant variability in its diurnal variations has been
      reported in normal subjects and in chronic obstructive pulmonary disease (COPD).
      In order to investigate whether passive smoking, active tobacco smoking, COPD and
      interstitial lung disease (ILD) are associated with changes in the circadian
      rhythm of PEF, five groups of adult male subjects, comparable for age, weight and
      height, were studied: group A: 30 clinically healthy subjects who never smoked,
      group B: 30 subjects passively exposed to tobacco smoking, group C 30 heavy
      smokers (> 20 cigarettes daily for at least 5 years), group D: 30 patients with
      nonasthmatic COPD (emphysema and/or chronic bronchitis), and group E: 15 patients
      with ILD (pneumoconiosis). Active tobacco smoking and exposure to passive smoking
      were assessed by the determination of the urinary cotinine concentration. A
      portable spirometer was used to measure PEF over a whole day, at 0.00, 6.00,
      8.00, 10.00, 12.00, 14.00, 16.00, 18.00, 20.00, 22.00, and 24.00 h, all subjects
      leading a normal life. The 'mean cosinor' method was used for statistical
      analyses; the PEF variability was evaluated by the amplitude percent mesor (daily
      mean). All groups showed diurnal fluctuations in PEF values with significant (p <
      0.05) circadian rhythms. The peaks of PEF rhythms occurred in the early
      afternoon, without significant (p > 0.05) differences between the groups. The
      cosinor mean was significantly (p < 0.05) lower in heavy smokers, in passive
      smokers, and in COPD patients than in controls. Controls, passive smokers, heavy
      smokers, COPD and ILD patients presented a PEF amplitude percent mesor (95%
      confidence limits) of 6.26% (range 4.57-7.95), 7.79% (range 5.07-10.51), 12.60%
      (range 7.61-17.59), 17.19% (range 10.18-23.50), and 3.98% (range 2.09-5.87),
      respectively, with significant differences (p < 0.05) between all groups, except
      between controls and passive smokers. These data suggest that tobacco smoke, both
      passive and active, does not modify the circadian peak of PEF, but modifies
      significantly its mesor and amplitude. In this respect, heavy smokers have the
      same pattern of COPD: lower mesor and greater amplitude; passive smokers present
      an intermediate situation. An increased diurnal variability in PEF could be
      considered as an early index of tobacco smoke damage and of developing COPD. When
      studying diurnal PEF variability, active and passive smoking habits should be
      considered.

PMID- 9257359
TI  - Maximal forced expiratory maneuver to measure airway obstruction in anesthetized
      guinea pigs.
AB  - Our purpose was to develop a method using a maximal forced expiratory flow (MFEF)
      for the study of airway hyperreactivity in guinea pigs induced by ovalbumin
      inhalation challenge. Eight guinea pigs (weight range 350-450 g) were sensitized
      by inhaled ovalbumin (group I) 2 times during a 1-week interval and then
      subjected to provocation with ovalbumin 1 week later. Pulmonary function tests at
      baseline and after acetylcholine challenge were performed 72 h later. Eight
      weight-matched normal guinea pigs served as controls (group II). All animals were
      anesthetized, paralyzed with gallamine, and ventilated via tracheostomy. They
      were given varying doses of acetylcholine (25, 50, 75, 100 micrograms/kg)
      injected through a jugular venous catheter. Five seconds after acetylcholine
      injections, pulmonary function was examined, including maximal forced expiratory
      maneuver, peak airway pressure (PaO) and total lung compliance. After completing
      the pulmonary function tests, bronchoalveolar lavage (BAL) was performed with 20
      ml normal saline divided into two doses. Thereafter, the lungs were removed and
      examined histologically. The results showed that guinea pigs treated with
      ovalbumin had worse pulmonary function tests than normal controls, characterized
      by lower peak flow, MFEF 75%, MFEF 50% and vital capacity. The ovalbumin
      presensitized guinea pigs also demonstrated severe bronchoconstriction in
      response to acetylcholine, characterized by larger decreases in peak flow, MFEF
      75%, MFEF 50% and in vital capacity than the control group. Total cell count, the
      percentage and absolute number of eosinophils and lymphocytes were increased, and
      the percentage of macrophages was decreased in the BAL fluid of these animals.
      Finally, ovalbumin-sensitized guinea pigs had a severe inflammatory reaction in
      airway and lung tissue, characterized by congestion, edema and inflammatory cell
      infiltration (especially lymphocytes and eosinophils) and desquamation of
      bronchial epithelial cells. In conclusion, a forced expiratory maneuver can be
      used to perform pulmonary function tests in guinea pigs.

PMID- 9257360
TI  - Breathing pattern and respiratory mechanics in chronically tracheostomized
      patients with chronic obstructive pulmonary disease breathing spontaneously
      through a hygroscopic condenser humidifier.
AB  - Hygroscopic condenser humidifiers (HCHs) have been proposed to artificially
      condition gases breathed by intubated and mechanically ventilated patients. These
      devices may improve viscosity and coloring of secretions, preventing further
      bacterial colonization, and heat inspiratory flow in chronically tracheostomized
      (CT) patients during spontaneous breathing. The aim of this study was to evaluate
      the effects of HCH on respiratory mechanics and breathing pattern in CT patients
      with chronic obstructive pulmonary disease (COPD) breathing spontaneously during
      quiet breathing and maximal voluntary ventilation (MVV). In a prospective,
      randomized, controlled study on 21 stable spontaneously breathing CT COPD
      patients, breathing pattern and respiratory mechanics were evaluated by means of
      a flow sensor and an esophageal pressure (Pes) catheter during quiet breathing in
      random order either with or without a HCH connected to the tracheostomy. Six of
      the patients were also studied during maximal voluntary ventilation (MVV). In
      comparison to without HCH, the application of HCH did not induce changes in the
      breathing pattern and respiratory mechanics during quiet breathing. As expected,
      in comparison to quiet breathing, MVV in 6 patients with HCH induced significant
      changes in respiratory frequency, minute ventilation, mean inspiratory flow, Pes,
      work of breathing, pressure time product and index. These changes were not
      significantly different without the application of HCH. In CT COPD patients
      spontaneously breathing. HCHs have no significant effects on the breathing
      pattern and respiratory mechanics both during quiet breathing and MVV.

PMID- 9257361
TI  - Clinical utility of a newly developed pressure swing adsorption-type oxygen
      concentrator with a membrane humidifier.
AB  - The clinical utility of the newly developed pressure swing adsorption (PSA)-type
      oxygen concentrator with a membrane humidifier that does not require added water
      for humidification was evaluated in 13 patients with chronic pulmonary disease
      who were receiving long-term oxygen therapy. PaO2 and the relative humidity were
      measured when the patient breathed air and oxygen from the new device via a nasal
      cannula. After using the new concentrator for 5 h, the patients were asked
      whether they experienced dry nasal passages or a dry throat. A significant
      difference between the PaO2 measured while the patients breathed room air and
      while they breathed oxygen from the new device was observed. A significant
      difference was observed between the relative humidity of room air (44.7 +/-
      18.6%) and that of the oxygen flow (72.7 +/- 14.8%) from the new device. None of
      the patients experienced dry nasal passages, dry throat, or any other adverse
      effects. Since this new PSA-type oxygen concentrator with a membrane humidifier
      supplies well-humidified nasal oxygen without water, laborious cleaning of the
      container and changing of the water are not necessary, and may help to improve
      the patient's quality of life.

PMID- 9257362
TI  - Therapeutic equivalence of a novel HFA134a-containing metered-dose inhaler and
      the conventional CFC inhaler (Berodual) for the delivery of a fixed combination
      of fenoterol/ipratropium bromide. A randomized double-blind placebo-controlled
      crossover study in patients with asthma.
AB  - The efficacy and safety of a novel fenoterol/ipratropium bromide metered-dose
      inhaler (MDI) formulated with a non-chlorinated propellant, HFA134a, has been
      compared with placebo and the conventional chlorofluorocarbon (CFC)-containing
      fenoterol/ipratropium bromide inhaler (Berodual) in asthmatic patients. Fifty-two
      patients were enrolled in two centres. The fenoterol/ ipratropium bromide
      treatment produced significantly (P < 0.0001) greater bronchodilatation than
      placebo. There were no significant differences between the mean peak and average
      forced expiratory volume in the first second (FEV1) for patients receiving 2
      puffs of the fenoterol/ipratropium bromide HFA134a inhaler and the conventional
      CFC inhaler. In addition, time to onset and duration of efficacy were comparable
      for these two treatments. None of the patients showed a fall of > or = 15% in
      baseline FEV1 or needed rescue medication within 30 min after inhalation of the
      test drug. No paradoxical bronchoconstriction was observed as measured by sGaw.
      The two inhaler formulations were well tolerated. A taste-related complaint,
      lasting for a few minutes after inhalation, was reported by a higher proportion
      of patients who inhaled the HFA134a formulation, mainly by patients selected in
      one of the two centres. In conclusion, a dose of 100 micrograms fenoterol/40
      micrograms ipratropium bromide inhaled from a MDI containing HFA134a propellant
      is safe and provides effective bronchodilatation of equivalent degree, onset and
      duration of action to the same dose from the conventional CFC formulation.

PMID- 9257363
TI  - Survival and cause of death among elderly chronic obstructive pulmonary disease
      patients after first admission to hospital.
AB  - Those patients with chronic obstructive pulmonary disease (COPD) who require
      hospital treatment are severely ill. We have studied the survival and cause of
      death among COPD patients in Finland after their first admission to hospital due
      to COPD. COPD-related treatment periods in all hospitals during 1972-1992 were
      collected from the national discharge register, and a subgroup was defined
      consisting of 2,237 patients aged 65-69 years who had their first admission
      during 1986-1990. Survival and causes of death were analysed for this group using
      the data contained in the national mortality statistics. The mortality data were
      recorded up to the end of 1993. By the end of 1993, 1,070 persons (48%) in the
      study group had died. The median survival time was 5.71 years (95% CI 5.27-6.15).
      Female COPD patients had a more favourable prognosis than males. COPD had been
      certified as the main cause of death for 33.3% of the women and 29.4% of the men.
      The proportion of COPD as main cause of death increased with an increasing number
      of treatment periods prior to death. In conclusion, the first hospital admission
      for COPD indicates a poor prognosis. A high incidence of pulmonary cancer
      contributes to the poor outcome in the case of men. COPD is obviously underrated
      on death certificates as the cause of death among COPD patients.

PMID- 9257364
TI  - Relationship between serum heat-stable neutrophil chemotactic activity during
      early airway reaction to allergen and the pattern of airway response (early
      versus late reactions) in asthmatic subjects.
AB  - In order to evaluate the relationship between allergen-induced heat-stable
      neutrophil chemotactic activity (HS-NCA) release during early asthmatic reaction
      (EAR) and the presence of a late asthmatic reaction (LAR), serum HS-NCA was
      measured at three serum dilutions (1:5, 1:40, 1:200) during EAR induced by
      allergen in 26 atopic asthmatics, 13 with isolated EAR and 13 with EAR followed
      by LAR. HS-NCA was measured using a 48-well microchamber with 5-micron-pore-size
      nitrocellulose filters, using isolated neutrophils from healthy donors and the
      leading front technique. Subjects with LAR developed EAR after inhalation of a
      lower dose of allergen than subjects with isolated EAR. Increase in serum HS-NCA
      during EAR was significantly higher in subjects with isolated EAR than in
      subjects with EAR plus LAR at the 1:5 dilution, while it was significantly higher
      in subjects with EAR plus LAR than in the subjects with isolated EAR at the 1:200
      dilution; the 1:40 dilution gave similar results in both groups. Changes in serum
      HS-NCA during EAR significantly correlated with the maximum decrease in forced
      expiratory volume in 1 s (FEV1) during LAR: a higher decrease in FEV1 during LAR
      was associated with a lower increase in HS-NCA at the 1:5 dilution (Spearman's
      rho = 0.43, rho = 0.03), and with a higher increase in NCA at the 1:200 dilution
      (Spearman's p = -0.46, p = 0.02). These results can be explained by the 'high
      dose-inhibition' phenomenon. Assuming that HS-NCA is associated with mast cell
      degranulation in the airways after allergen challenge, these findings demonstrate
      that higher mast cell activation during EAR is present in subjects with a
      subsequent LAR than in subjects with isolated EAR.

PMID- 9257365
TI  - Aspergillus fumigatus Asp fI DNA is prevalent in sputum from patients with coal
      workers' pneumoconiosis.
AB  - Aspergillus fumigatus is an apportunistic nosocomial pathogen in immunosuppressed
      patients or in the lesion where the local defense mechanism was impaired.
      Patients with pneumoconiosis are known to be susceptible to chronic necrotizing
      pulmonary aspergillosis. Therefore, we hypothesized that A. fumigatus might be
      prevalent in sputum from patients with coal workers' pneumoconiosis, and also
      that asthmatic symptoms in patients with coal workers' pneumoconiosis may be
      associated with the presence of A. fumigatus. We tested for A. fumigatus in the
      sputum from patients with coal workers' pneumoconiosis by nested polymerase chain
      reaction amplification of the Asp fI gene. Sequences specific for this gene were
      detectable in 5 of 11 (45.5%) patients with coal workers' pneumoconiosis with
      asthmatic symptoms (group A), 5 of 10 (50.0%) patients with coal workers'
      pneumoconiosis without asthmatic symptoms (group B) and only 1 of 9 (11.1%)
      patients with chronic airflow obstruction without pneumoconiosis (group C). The
      frequency of the Asp fI gene detection was significantly higher in groups A and B
      than in group C (p < 0.05). The prevalence of A. fumigatus was not associated
      with asthmatic symptoms. These results demonstrated that A. fumigatus was
      prevalent in patients with coal workers' pneumoconiosis. We speculate that
      colonization with A. fumigatus may be associated with this disease.

PMID- 9257366
TI  - Atypical locations of pulmonary tuberculosis and the influence of the
      roentgenographic patterns and sample type in its diagnosis.
AB  - In 97 cases of pulmonary tuberculosis (PTB), we analyzed the incidence of
      atypical roentgenographic locations, roentgenographic patterns, the correlation
      between the diagnostic yield and the roentgenographic pattern and the usefulness
      of simple or induced sputum (82 cases), bronchoaspirate (BAS; 29 cases),
      postfiberoptic bronchoscopy sputum (PFBS; 16 cases) and how the different tests
      supplemented each other. Atypical locations were defined as those not
      corresponding to classic primary and postprimary PTB. This atypical-location PTB
      index was 8.2%, and roentgenographic patterns found most frequently were:
      destructive 52.5%, destructive-alveolar 20.6% and alveolar 12.3%. Lowenstein
      Jensen (LJ) culture of the sputum of alveolar-pattern cases improved acid-fast
      bacillus (AFB) diagnosis by 46% (p < 0.005), in contrast to other radiologic
      patterns. Simple or induced sputum proved to be a very good diagnostic specimen
      in 98% of the cases (AFB staining 73.1% and LJ culture 89%). BAS increased the
      sputum yield by 21% and PFBS contributed only 1 additional case to the results
      obtained with BAS. Therefore, BAS is a very good supplemental test in cases of
      false-negative findings.

PMID- 9257367
TI  - Pulmonary infection due to Mycobacterium gordonae in an adolescent
      immunocompetent patient.
AB  - We report the case of 17-year-old male adolescent immunocompetent patient with an
      operated transposition of the great arteries after the Mustard technique admitted
      to our hospital because of a cough and hemoptysis. Two nodules and an area of
      ground glass appearance located in the lower lobe of the left lung were diagnosed
      by ultrafast computed tomography (UF-CT) after ruling out cardiovascular
      complications. The gastric aspirate revealed acid-fast bacilli despite a
      repeatedly negative tuberculin skin test identified as Mycobacterium gordonae by
      the Gen-Probe Rapid Diagnostic Test. After an initial standard antimycobacterial
      therapy with isoniazid, rifampin and pyrazinamide the therapy was changed to
      clarithromycin and after a treatment course of 14 days, the UF-CT revealed a
      normal scan of both lungs. The case described suggests that one has to consider
      M. gordonae as a rare cause of infection even in immunocompetent patients.

PMID- 9257368
TI  - Disseminated pulmonary granulomas after intravesical bacillus Calmette-Guerin
      immunotherapy.
AB  - Intravesical instillation of bacillus Calmette-Guerin (BCG) vaccine has been
      shown to be an effective treatment of superficial bladder cancer. However, it is
      not free of side-effects and complications. We present the case of a 62-year-old
      man who developed disseminated pulmonary granulomas after local BCG immunotherapy
      for recurrent papillary bladder cancer.

PMID- 9257369
TI  - Fatal diffuse alveolar damage from bird fanciers' lung.
AB  - A 68-year-old man, who had continuing exposure to budgerigars, developed fatal
      acute respiratory failure following years of slowly progressive pulmonary
      deterioration. His lung function was characterized first by mild airflow
      obstruction and later by progressive loss of lung volume. Computed tomography
      showed progressive development of pulmonary fibrosis and honeycombing. His serum
      disclosed precipitins to pigeon antigen. During his final illness his chest
      radiograph showed widespread patchy consolidation. At autopsy, his lungs revealed
      left lower lobe bronchopneumonia, fibrosis and honeycombing at the bases and
      widespread evidence of diffuse alveolar damage with organized exudate in some
      alveoli. To our knowledge, this is the second reported fatality due to acute
      alveolar injury in bird fanciers' lung.

PMID- 9257371
TI  - Primary purulent mediastinitis due to Streptococcus milleri.
AB  - Streptococcus milleri mediastinitis had resolved in a 44-year-old male after 3
      weeks of combined parenteral antibiotic therapy including clindamycin, which
      showed the greatest in vitro activity against S. milleri isolated from this
      patient, and surgical drainage. This case demonstrates that primary purulent
      mediastinitis may be caused by a strain of S. milleri with or without other
      bacterial species, and suggests that S. milleri should be added to the list of
      causative organisms of purulent mediastinitis even when the patient has not
      undergone a surgical procedure.

PMID- 9257370
TI  - Interstitial pneumonitis and fibrosis associated with the inhalation of hair
      spray.
AB  - We describe a 49-year-old female Japanese hairdresser who presented with a 5-year
      history of exertional dyspnea, a nonproductive cough, and occasional febrile
      episodes. Histological analysis revealed interstitial fibrosis with mononuclear
      cell infiltration, foreign body granuloma, and numerous intra-alveolar
      macrophages and multinucleated giant cells of foreign body type. Arterial blood
      gas, pulmonary function studies and computed tomographic findings demonstrated
      improvement 6 months after cessation of exposure to the salon. Bronchoalveolar
      lavage fluid findings suggested that the development of lung disease in this case
      was triggered by an allergic mechanism rather than the storage of hair spray
      ingredients in the lung.

PMID- 9257372
TI  - Aggressive pulmonary metastasectomies for synovial sarcoma.
AB  - A 51-year-old woman underwent a bilateral wedge resection of lung metastases
      through a median sternotomy 10 months after an initial operation for synovial
      sarcoma of the left lower extremity. Since then, five right and two left
      posterolateral thoracotomies have been performed over a 6-year period. The
      patient is presently doing well 7 years after the initial operation of the left
      lower extremity without any evidence of recurrence.

PMID- 9257373
TI  - Immunological gene therapy approaches for malignant melanoma. 1. Tumor
      immunological background.
AB  - Gene therapy approaches pursuing immunological strategies for the treatment of
      malignant melanoma play major roles in the current efforts to explore the
      potential benefits of gene transfer technologies for medicine. This may be
      explained by the nearly complete resistance of advanced metastatic melanoma
      towards conventional non-surgical treatment modalities, and the particular
      immunogenicity of melanoma in connection with a presumed immuno-gene therapeutic
      'field effect'. The latter relates to the potency of the immune system to amplify
      gene transfer effects that are limited due to the imperfection of the currently
      available gene delivery systems. The ongoing clinical trials focus predominantly
      on treatment safety and tolerability rather than efficacy. The corresponding
      tumor-immunological background is reviewed, focusing on a treatment concept
      centred on tumor-reactive, cytotoxic CD8+ T effector cells.

PMID- 9257374
TI  - A skin equivalent model for cosmetological trials: an in vitro efficacy study of
      a new biopeptide.
AB  - The European Community directive, imposing that effects claimed for cosmetic
      actives must be validated using non-animal procedures, has stimulated the use of
      in vitro models for pharmacotoxicological trials. In this paper, an efficacy
      study of a new biopeptide, a hydrolysate obtained by fermentation of milk
      proteins, was performed using an in vitro skin equivalent (SE). This SE is
      obtained by seeding normal human keratinocytes onto a dermal equivalent
      comprising a collagen-glycosaminoglycan(GAG)-chitosan porous matrix populated by
      normal human fibroblasts, which neosynthesize their own extracellular matrix
      (ECM). A gel containing 2% milk biopeptide was applied topically (10 microliters)
      every 2 days during 15 days. Subsequent investigations of the biopeptide effects
      were based on morphological criteria after histological analysis and on synthesis
      of ECM components. Collagen and GAG synthesis were measured by tritiated proline,
      glucosamine and Na2(35)SO4 incorporation. Qualitatively, the histological
      features of the biopeptide-treated SEs showed a thicker epidermis than the
      untreated control SEs, where only a few layers of stratum corneum were observed.
      The dermal porous matrix seems to be more filled by neosynthesized ECM than the
      control. Quantitatively, milk biopeptide treatment induced a significant
      activation of hyaluronic acid (+46%) and sulfated GAG (+53%) synthesis, whereas
      only non-significant increases of total protein and collagen synthesis were
      observed (Student's test, p < 0.001).

PMID- 9257375
TI  - Bisindolylmaleimide protein-kinase-C inhibitors delay the decline in DNA
      synthesis in mouse hair follicle organ cultures.
AB  - We have used a series of bisindolylmaleimide selective protein-kinase C (PKC)
      inhibitors to investigate the role of this enzyme in the regulation of cell
      proliferation in mouse hair follicle organ cultures. Mouse whisker follicles were
      isolated by microdissection, and rates of DNA synthesis during culture were
      determined from 3H-thymidine incorporation. The bisindolylmaleimides Ro 31-7549,
      Ro 31-8161, Ro 31-8425 and Ro 31-8830 inhibit isolated brain PKC with IC50 values
      of 8-80 nM, are > 60-fold less potent against protein kinase A, and inhibit PKC
      mediated protein phosphorylation in platelets with IC50 values in the range 0.25
      4.4 microM. These PKC inhibitors were found to increase levels of mouse hair
      follicle DNA synthesis, with EC50 values in the range 1-4 microM and maximal
      levels in the range 151-197% of control. Ro 31-7549 had an IC50 value 50-fold
      lower than that of minoxidil, while the maximal level of DNA synthesis for the
      PKC inhibitor was 86% higher. Incubation of mouse hair follicles with Ro 31-7549
      resulted in a delay of approximately 24 h in the onset of decline in follicular
      DNA synthesis rates. Ro 31-6045 and Ro 31-7208, bisindolylmaleimides without
      activity in the platelet PKC assay, did not affect mouse hair follicle DNA
      synthesis rates. Taken together, these findings show that PKC mediates, at least
      in part, the rapid loss of proliferative activity that occurs in mouse whisker
      follicles in culture, and provide further evidence that PKC plays a role as a
      negative proliferative signal in hair follicles.

PMID- 9257376
TI  - Cyclosporin G inhibits proliferation of A431 cells in a dose- and time-dependent
      manner comparable to cyclosporin A.
AB  - Cyclosporin A (CyA), a fungal metabolite with potent immunosuppressive activity
      and an antiproliferative effect on epithelial cells, i.e. normal and transformed
      keratinocytes, is currently proposed in the treatment of psoriasis, where its use
      is limited mainly by possible nephrotoxicity and/or hepatotoxicity. Numerous
      analogs of CyA have been produced and studied. The most promising of these is the
      immunosuppressive analog cyclosporin G (CyG), in which norvaline is substituted
      for alpha-aminobutyric acid at the 2 position. This would maintain strong
      immunological activity, with reduced to absent nephrotoxic and hepatotoxic
      effects. The authors compared the antiproliferative effect of CyG and CyA on the
      epidermoid carcinoma cell line A431 in vitro, performing the MTT-microculture
      tetrazolium colorimetric assay based on the ability of viable cells to reduce the
      MTT compound to a blue formazan product. Subconfluent A431 cells were incubated
      with CyA or CyG or solvent only, for 24, 48, 72 or 96 h at concentrations of in
      vivo relevance (0.3, 0.6, 1.25, 2.5, 5, 7.5, 10 micrograms/ml). CyA and CyG
      showed similar antiproliferative effects, in low-serum-containing media in a dose
      and time-dependent manner. After 24 h of incubation, the inhibition of the
      growth rate was irrelevant. A striking inhibition of the growth rate at the
      higher concentrations of the drugs (7.5 and 10 micrograms/ml) at 72 and 96 h of
      incubation was evident. Therefore CyG has been demonstrated to exercise an
      antiproliferative effect on the A431 cell line. These data suggest possible use
      for CyG in the treatment of immune-mediated disease, particularly in the
      treatment of dermatologic diseases characterized by epidermal hyperplasia and/or
      keratinocyte hyperproliferation.

PMID- 9257377
TI  - Topical retinol and the stratum corneum response to an environmental threat.
AB  - The functional consequences of using topical retinol on skin have not been
      thoroughly studied so far. The aim of this open study was to compare two
      preparations containing either retinol or vitamin E, using biometric evaluations.
      Three methods, namely the sodium lauryl sulfate (SLS) corneosurfametry bioassay,
      the ultraviolet (UV) squamometry test and optical profilometry of the UV-induced
      wrinkling process, were used to assess some properties of the stratum corneum.
      The retinol preparation achieved better scores than the vitamin-E cream in all
      three tests and appears to improve the resistance of the stratum corneum against
      some chemical (SLS) and physical (UV) threats. It also limits UV-induced shallow
      wrinkling.

PMID- 9257378
TI  - The effect of tamol on human mast cell chymase and plasmin.
AB  - Tamol is widely used in the therapy of inflammatory dermatoses. It has pronounced
      astringent properties and is able to inactivate the neutrophil-derived elastase.
      Since plasminogen activation and release of mast cell chymase may occur in acute
      dermatitis, we investigated the inhibitory properties of tamol for these enzymes.
      Tamol proved to be a potent inhibitor of plasmin and mast cell chymase in
      concentrations relevant for use in dermatotherapy. The inhibition of mast cell
      chymase and plasmin by tamol was linear and non-competitive. The inactivation of
      proteolytic enzymes with the capacity to degrade extracellular-matrix proteins
      may be one of the major clinical effects of tamol in the treatment of acute
      inflammatory dermatoses.

PMID- 9257379
TI  - Oxyhemoglobin is a quantifiable measure of experimentally induced chronic
      tretinoin inflammation and accommodation in photodamaged skin.
AB  - Chronic exposure to a weak irritant leads to inflammatory changes which may be
      followed by pigmentary changes and accommodation. The inflammatory responses to
      acute exposure to an irritant have been extensively studied. This study
      investigated quantitatively the inflammatory reactions produced in photodamaged
      skin with chronic application of a weak chemical irritant (tretinoin cream
      0.025%) over a period of 9 months (36 weeks). Forty-eight subjects with
      moderately to severely photodamaged skin were enrolled in a 36-week, double-blind
      placebo-controlled study. Tretinoin cream was applied nightly on the distal two
      thirds of one dorsal forearm and placebo on the other. The proximal third of each
      dorsal forearm received no treatment and served as control. Clinical assessments
      and diffuse reflectance measurements were made at 7 time points during treatment.
      Apparent concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and melanin
      were estimated by analysis of the diffuse reflectance spectra. No changes were
      observed in the apparent HbO2 or the Hb concentration of the placebo-treated or
      control sites, thus establishing a reliable baseline. The apparent HbO2
      concentration of the tretinoin-treated sites increased significantly from
      baseline to a maximum at 12-18 weeks of treatment, then returned to baseline with
      continued applications. The changes in HbO2 concentration agreed closely with
      clinical assessments of erythema. The apparent melanin concentration,
      corresponding to diffuse hyperpigmentation, showed a large seasonal decrease in
      both the control and the treated sites, with an additional decrease in the
      treated sites between 12 and 18 weeks. Erythema appeared after repeated
      applications and eventually resolved under continuous treatment. The maximum
      decrease in hyperpigmentation occurred simultaneously with the maximum increase
      in erythema.

PMID- 9257390
TI  - The economic cost of homicide in New Zealand.
AB  - Violence has become increasingly recognised as a public health issue, with
      significant impact on the health of individuals. In addition, there is increasing
      awareness that there are substantial economic costs associated with violence. The
      present study estimated the economic costs associated with homicide in New
      Zealand, using a human capital approach. Direct costs were assessed using
      information on incidence and costs from government agencies, and indirect costs
      were assessed based on loss of productivity resulting from death. The total
      estimated cost of homicides in 1992 was NZ $82997065 (U.S. $53948092), averaging
      NZ $1012159 per homicide (U.S. $657903). This total was comprised of the
      estimated total cost associated with homicide victims of NZ $37017010 (U.S.
      $24061056) and the estimated total cost associated with homicide perpetrators of
      NZ $45980055 (U.S. $29887035). Limitations of the incidence data and the methods
      employed suggest that these costs are likely to be underestimates. Nevertheless,
      the figure calculated represents an enormous drain on New Zealand's economic
      resources.

PMID- 9257391
TI  - Why women say yes to prenatal diagnosis.
AB  - Despite considerable concern of bioethicists, disabilities rights activists,
      feminists and others about the spread of prenatal diagnostic technologies, their
      routine acceptance in many parts of the world continues at a rapid pace. Yet,
      there is wide variation by country and region in rates of acceptance of prenatal
      diagnosis. We draw on John McKinlay's model of how a medical innovation becomes
      routinized to explore the circumstances that led to the widespread use of one
      prenatal diagnostic screen-the maternal serum alpha fetoprotein (MSAFP) test for
      the detection of neural tube defects and other developmental disabilities. As
      predicted by McKinlay's model, analysis of published data suggests that strong
      institutional or provider support is the best predictor of women's level of MSAFP
      test acceptance. Data collected at a health maintenance organization in
      California illuminate the processes through which medico-legal and institutional
      forces affect the use of MSAFP screening. By examining the language women use to
      talk about MSAFP screening, we show how providers also shape women's
      understandings of the meaning and purpose of MSAFP screening. These data
      ultimately shed light on how the very ethical issues which concern critics of
      prenatal diagnosis become obscured in the processes by which this screening test
      becomes accepted as routine.

PMID- 9257392
TI  - Pneumonia perceptions and management: an ethnographic study in urban squatter
      settlements of Karachi, Pakistan.
AB  - Childhood pneumonia continues to be the second highest contributor to childhood
      morbidity and mortality in all ethnic groups in Pakistan. Information on
      community perceptions and management is largely limited to the Punjabi populace.
      In this study, ethno-specific illness terminologies, recognition and severity
      indicators and resort to treatment options for childhood pneumonia are explored
      among the two main ethnic groups in Sindh. Results are based on focus group
      discussions with 90 caretakers and 16 case history interviews. The findings
      indicate that pneumonia recognition is almost universal. The main recognition and
      severity indicator was pasli chalna (chest indrawing) followed by signs and
      symptoms relating to the quality of breathing and presence of high fever,
      lethargy and anorexia. Recognition of rapid breathing was low and mostly
      associated with fever. Exposure to thand (cold) through a variety of mechanisms
      was perceived to be the dominant causal model. The concept of contagion was
      virtually non-existent. Despite this, belief in efficacy of allopathic care was
      very high. Most caretakers reported seeking outside care within one to three days
      of the onset of symptoms. However, unrealistic expectations of cure often led to
      change in physicians and treatment regimen, if no improvement was observed by the
      second day. On the other hand, the quality of care provided by the physicians
      (both licensed and unlicensed) left much to be desired. Female autonomy and
      mobility did not appear to be a major constraint in seeking outside care other
      than for hospitalisation. Implications of these findings for the national acute
      respiratory infections control programme and future research are discussed

PMID- 9257393
TI  - "Painting a Leonardo with finger paint": medical practitioners communicating
      about death with aboriginal people.
AB  - This article describes 19 semi-structured interviews with medical practitioners
      working in the Northern Territory of Australia. The interviews explored the
      practitioners' perceptions of the differences between Aboriginal and Western
      beliefs about disease causation and death. The interviews further explored how
      these perceptions affected the practitioners' communication of mortality
      information and their response to the practical and legal tasks of reporting
      deaths to the coroner, requesting postmortems and certifying death. Two key
      themes emerged. The first was the variety of interpretations placed by medical
      practitioners on the concept of "respect", and the difficulty they had in showing
      that respect in light of competing Western legal and professional obligations.
      The second theme was that medical practitioners felt that Aboriginal people's
      notions of "blame" did not match their own; this led some medical practitioners
      to become despondent, whilst others negotiated this tension creatively. Use of
      the word "blame" almost solely to refer to the Aboriginal discourse served to
      exoticise the Aboriginal process and obscure its areas of similarity with the
      Western discourse of "responsibility".

PMID- 9257394
TI  - Caregiving: a common or uncommon experience?
AB  - The analysis reported here aims to establish the household prevalence of
      caregiving in Australia, drawing on a large scale, longitudinal survey conducted
      as part of the Victorian Carers Project. Comparisons are made with a national
      survey conducted by the Australian Bureau of Statistics and with Canadian and
      U.K. findings. Three aspects of caregiving are investigated: reported household
      prevalence, taking account of differences in definitions used in various surveys;
      the extent of intergenerational exchanges involved in caregiving; and the time
      dimensions of caregiving, in terms of duration and patterns of cessation of
      caregiving over time. A high degree of consistency is found in prevalences of
      caregiving and implications for the development of policies and programs to
      support caregivers are raised concerning levels of caregiving, approaches to
      identifying carers, targeting of services and promotion of caregiving, and the
      spread of the experience of caregiving across the lifecycle and between
      generations.

PMID- 9257395
TI  - Infant mortality among various nationalities in the middle part of Guizhou,
      China.
AB  - This paper describes infant mortality, leading causes of death, and some
      associated factors among the Han, the Miao, the Bouyei and other minority
      nationalities in three counties of the middle part of Guizhou Province, China.
      The results showed that the overall infant mortality rate (IMR) in these areas
      was 125.7 per 1000 live births during 1985-1987. There existed a great disparity
      in IMR among different nationalities. The rate was 103.1 (Han), 148.8 (Miao),
      161.2 (Bouyei) and 145.0 (other ethnic groups) per 1000 live births,
      respectively. The five leading causes of death in infants were respiratory
      diseases, neonatal tetanus, birth asphyxia, infectious diseases and diarrhoea.
      These causes of death combined resulted in an IMR of 104.1 per 1000 live births.
      However, these diseases varied in importance for infants of different
      nationalities. We considered the relationship between infant death and maternal
      and child health care. The location of birth, the kinds of birth attendants and
      utilization of health facilities might be associated with differentials of infant
      mortality among these nationalities. Maternal education was associated with
      infant survival, but it might not be the only factor in decreasing or eliminating
      the differential of IMR among various nationalities. Based upon the findings, it
      is urgent to improve maternal and child health care and investigate further
      cultural and sociological factors among various nationalities.

PMID- 9257396
TI  - Modern medicine and the "uncertain body": from corporeality to hyperreality?
AB  - This paper (re)considers the role of medical technology at three interrelated
      levels: first, the extent to which medical technology renders our bodies
      increasingly "uncertain" at the turn of the century; second, the analytical
      purchase which the notion of the (medical) cyborg provides regarding contemporary
      forms of human embodiment; and finally, at a broader level, the issues this
      raises in relation to a (late) modernist or postmodernist reading of contemporary
      medical practice. Key themes here include the plastic body, the bionic body,
      communal/interchangeable bodies, (genetically) engineered/ chosen bodies, and
      virtual bodies. The paper concludes with a critical appraisal of these themes and
      issues, arguing for a late modernist position on medical technology as both a
      positive and negative rationalising force, and a "life political agenda" in which
      the "all-too-human" quality of human nature is seen as inviolable.

PMID- 9257397
TI  - Quality of life and social production functions: a framework for understanding
      health effects.
AB  - Quality of life (QofL) has emerged as a new outcome paradigm. It is now the
      endpoint in various taxonomies of patient outcomes, in which relationships are
      modeled amongst biological abnormalities, symptom status, functional status,
      disability, health perceptions and quality of life. Although current models and
      taxonomies point at important determinants of QofL, they do not provide a
      heuristic that guides the conceptualization of QofL and the systematic
      development of an explanatory theory of how ill health affects QofL. General
      mechanisms linking ill health, behavior, and QofL are lacking. In this paper we
      propose social production function (SPF) theory as providing such a heuristic,
      relating the effects of ill health, the activities that patients engage in to
      maintain QofL, and QofL itself. This theory basically asserts that people produce
      their own well-being by trying to optimize achievement of universal human goals
      via six instrumental goals within the environmental and functional limitations
      they are facing. Three important notions of SPF theory are: (1) the linkages
      between goals, needs, and well-being; (2) the distinction between universal needs
      and instrumental goals; and (3) substitution among instrumental goals, activities
      and endowments according to cost-benefit considerations, whereby costs refer to
      scarce resources such as functional capacity, time, effort and money. We will
      argue that SPF theory meaningfully relates the "biomedical model"-with its focus
      on pathological processes and biological, physiological and clinical outcomes-to
      the "quality of life" model, with its focus on functioning and well-being. We
      describe SPF theory and how SPF theory can be used to: (1) operationally define
      and measure QofL; (2) clarify persistent measurement problems; and (3) develop an
      explanatory framework of the effects of disease on QofL. In the discussion
      section, we address the limitations of the SPF approach of QofL and its
      relationship with personality.

PMID- 9257398
TI  - Traditional medicine in contemporary Ghana: a public policy analysis.
AB  - Discourses on the future of traditional medicine in Africa and other indigenous
      societies often assume government recognition and integration into the formal
      health care systems. There is very little attempt, however, to understand the
      contexts in which the knowledge and practice of traditional medicine are
      currently reproduced, let alone the social, economic and cultural factors that
      determine consumer choices. Based on the participant observation combined with in
      depth interview method, a longitudinal study was designed to determine the longer
      term trends in the reproduction of the knowledge and practice of traditional
      medicine in contemporary Ghana. This preliminary report covers: socio-economic
      conditions of the typical village practitioner, their belief systems and how that
      affects practise orientation; and perceptions as to whether traditional medicine
      could be taught and practised as part of the formal health care sector. This
      paper highlights some of the key issues which policy-makers may wish to explore
      with regard to the future of traditional medicine in Ghana and other African
      countries. These include: the role of "spiritually based" traditional
      practitioners in the provision of care, especially for people with mental health
      and other psychosocial problems; professional relationships between the
      biomedically trained and the traditional practitioner, particularly with regards
      to policies aimed at integrating traditional medicine into the formal health
      sector; equity of access, given that efforts to "control" the quality of herbal
      preparations through biomedical research can dramatically alter costs, thereby
      undermining ease of access normally associated with traditional medicine; a need
      to re-examine underlining reasons for the current popularity of traditional
      medicine in Ghana and other African countries, given the fact that the
      introduction of user pay services may be forcing the poor to sometimes turn to
      obsolete therapeutic practices in the name of "traditional medicine"; and
      potential public health benefits accruing from better understanding of
      traditional African notions of illness causation and preventative health.

PMID- 9257400
TI  - Urban small area variation in adolescents' health behaviour.
AB  - Our previous study indicated that region plays a relatively small role in
      adolescents' health behaviour. Here, the regional patterning of health behaviour
      is studied further by shifting the focus to small areas. First, we test whether
      small area socioeconomic, demographic and housing characteristics correlate with
      health behaviour. The analysis then turns to the relationship between these
      characteristics and their individual level correlates. We wish to ascertain if
      behaviour is related to small area characteristics similarly for both genders and
      for adolescents' socioeconomic characteristics. The Adolescent Health and
      Lifestyle Survey data from 1989-1995 (16- and 18-year-olds, n = 1048, response
      rate 71%) were linked with data describing 33 subareas of Helsinki, the capital
      of Finland. Smoking, alcohol use, abstention from dietary fat and physical
      activity were used as lifestyle indicators. Gender apparently influences the
      extent to which the area plays a role. Logistic regression demonstrated that
      prolonged unemployment predicted low prevalence of abstention from dietary fat
      (traditional dietary patterns) among girls and heavy drinking among boys. High
      total rate of unemployment predicted lower physical activity among girls. Also
      owner-occupied housing correlated positively with girls' physical activity.
      Although the individual level socioeconomic characteristics were not as strongly
      related to health behaviour as the small area factors, a low level of education
      predicted smoking and alcohol use and, among girls, decreased physical activity.
      We conclude that small area characteristics, especially the level of unemployment
      of the area, may be even more strongly related to health behaviour than
      individual socioeconomic characteristics.

PMID- 9257399
TI  - The "race" concept in smoking: a review of the research on African Americans.
AB  - This paper presents an analysis of the "race" concept as used by researchers who
      have studied the smoking behavior of African Americans. Most researchers in the
      field have failed to address the conceptual dimensions and meanings of "race" and
      accept uncritically the use of the term. This practice is viewed as an impediment
      in explaining inter- and intra-racial group differences and intervening
      effectively to reduce consumption of tobacco products. Adopting the majority
      minority intergroup relations paradigm, the conceptual and practical meanings of
      "race" are reviewed by focusing on the history of relations between blacks and
      tobacco, conceptions of "race," "biology" and cigarette smoking, and the
      sociological nucleus (e.g. social class, racism and culture) of "race." Genetic
      or biologic assumptions and meanings of "race" in research on the smoking
      behavior of African Americans are critically examined. It is argued that "race"
      is a dynamic social construct reflecting societal transformations in relations
      between racially classified social groups (RCSGs).

PMID- 9257401
TI  - Perceived work conditions and work-related symptoms among employed Finns.
AB  - The aim of the study was to determine the number and nature of perceived harmful
      work conditions and perceived work-related symptoms among employed Finns by sex
      and socioeconomic group. The associations between perceived harmful work
      conditions and perceived symptoms were also investigated. Knowledge of perceived
      work-related ill health can serve as a basis for health promotion at work. In a
      computer-assisted telephone interview of 2744 salaried employees and wage
      earners, the respondents were asked about perceived harmful work conditions as
      well as perceived health complaints, and their relatedness to work. At least one
      harmful factor at work was reported by 94% of the respondents, and half of them
      reported more than three such factors. The most commonly occurring harmful
      factors were increased work pace, mental demand, repetitive movements, and noise.
      Of the symptoms perceived as work-related, musculoskeletal symptoms were the most
      common. They were reported by 44% of the respondents, followed by mental symptoms
      (26%), psychosomatic symptoms (19%), and respiratory or sensory symptoms (15%).
      Both the reporting of perceived harmful work factors and perceived work-related
      symptoms varied by socioeconomic group and sex. Perceived work-related
      musculoskeletal symptoms were associated with perceived ergonomic harmful work
      factors among both the men and the women, with physical or chemical work factors
      among the men, and with psychosocial or work organizational factors among the
      women. Perceived work-related respiratory symptoms were associated with perceived
      harmful physical or chemical work factors among both the men and the women, and
      both groups also reported mental and psychosomatic symptoms in relation to
      harmful psychosocial or organizational work factors. Among the women
      psychosomatic symptoms and harmful ergonomic work factors were also related.
      Perceived harmful factors at work and work-related symptoms are common among the
      work force. Even though the degree of work-related ill health was related to
      socioeconomic group, the reporting of particular symptoms indicated the
      probability of a particular work factor being considered harmful independently of
      socioeconomic group, although there was some relationship to sex. The
      implications for occupational health services are evident; employees' work
      related symptoms can serve as an indicator of (preventable) perceived problems at
      work.

PMID- 9257402
TI  - Chronic work stress, sickness absence, and hypertension in middle managers:
      general or specific sociological explanations?
AB  - The issue of differential prediction of health outcomes by sociological models of
      work stress has received little attention so far. This paper argues, both on
      theoretical and empirical grounds, that active coping with the experience of
      chronic work stress is more likely to be associated with physical health
      consequences of sustained autonomic arousal such as hypertension, whereas passive
      coping may predispose individuals to withdrawal behavior such as sickness absence
      from work. Based on data from a cross-sectional study on 189 male middle-aged (40
      55, 48.3 +/- 4.6 years) middle managers in a car-producing company in Germany,
      this hypothesis is tested in the framework of the theoretical model of effort
      reward imbalance at work. More specifically, the simultaneous manifestation of
      high effort and low reward at work, indicative of active coping, is expected to
      statistically predict the risk of being hypertensive. Conversely, suffering from
      low occupational rewards in the absence of signs of sustained effort, indicative
      of passive coping, is expected to predict sickness absence (SA) behavior.
      Multivariate odds ratios (OR) derived from logistic regression analysis and
      adjusted for important confounders indicate that three measures of low reward are
      associated with short-term SA (OR ranging from 3.30 to 9.15), that one measure of
      low reward is associated with long-term SA (OR: 2.67) and that two measures of
      low reward are associated with number of SA episodes (OR 4.05 and 6.33), whereas
      no indicator of high effort at work is significantly associated with SA. On the
      other hand, the OR of being hypertensive is 5.77 in middle managers who suffer
      from high effort and low reward simultaneously. In conclusion, a sociological
      model of work stress which allows for differential prediction of health outcomes
      according to the important notions of active versus passive coping with work
      demands finds preliminary empirical support.

PMID- 9257403
TI  - The relationship of income inequality to mortality: does the choice of indicator
      matter?
AB  - Ecologic studies in the U.S. and elsewhere in the world have demonstrated that
      income inequality is strongly related to mortality and life expectancy: the
      greater the dispersion of income within a given society, the lower the life
      expectancy. However, these empirical studies have been criticized on the grounds
      that the choice of indicator may have influenced positive findings. Using a cross
      sectional, ecologic design, we tested the relationships of six different income
      inequality indicators to total mortality rates in the 50 U.S. states. The
      following summary measures of income distribution were examined: the Gini
      coefficient; the decile ratio; the proportions of total income earned by the
      bottom 50%, 60%, and 70% of households; the Robin Hood Index; the Atkinson Index;
      and Theil's entropy measure. All were highly correlated with each other (Pearson
      r > or = 0.94), and all were strongly associated with mortality (Pearson r
      ranging from 0.50 to 0.66), even after adjustment for median income and poverty.
      Thus, the choice of income distribution measure does not appear to alter the
      conclusion that income inequality is linked to higher mortality. Furthermore,
      adjustment for taxes and transfers, as well as household size (using equivalence
      scales), made no difference to the income inequality/mortality association. From
      a policy perspective, the alternative income distribution measures perform
      differently under varying types of income transfers, so that theoretical
      considerations should guide the selection of an indicator to assess the impact of
      social and economic policies that address income inequality.

PMID- 9257404
TI  - Contingent legitimacy: U.K. alternative practitioners and inter-sectoral
      acceptance.
AB  - Although alternative medicine has achieved an increasingly high profile in recent
      years, surprisingly little social research has been conducted in the area. This
      is noticeably the case when considering inter-sectoral contact and collaboration.
      This paper fills that gap by drawing on evidence from a large-scale study of non
      orthodox practitioners in the U.K. By examining the lived experience of
      interaction the study aimed to discover the level of professional legitimacy
      which alternative practitioners routinely enjoy or are denied by mainstream
      practitioners. Results show that the last decade has been characterised by an
      increasing liberalisation of attitude toward inter-sectoral collaboration
      throughout the mainstream. However, the evidence also shows that this cannot be
      equated with the existence of a generalised acceptance of alternative
      practitioners, professional legitimacy. There is a schism within orthodoxy on
      this issue and that schism is occupationally based: at the extremes, consultants
      remain characteristically dismissive of alternative practitioners, nurses
      overwhelmingly enthusiastic. The nature of the non-orthodox practice being
      considered was of little significance. It is argued that the identification of
      differentiation within orthodoxy on this issue marks a significant point in
      developing an understanding of relations between the "sectors" and its component
      parts. There is a clear potential for conflicting developmental paths of action
      between orthodox groups, and for differing conceptions of who and what constitute
      a legitimate part of the medical totality. Cross-sectoral alignments, which
      challenge the state sanctioned dichotomy of mainstream/alternative, are viewed in
      quite different ways throughout orthodoxy. Knowledge of this intra-sectoral
      differentiation is essential to an understanding of emerging patterns of inter
      sectoral relations.

PMID- 9257405
TI  - Role concepts and expectations of physicians and nurses in hospitals.
AB  - The social environment in which hospitals in the Netherlands have to function
      nowadays is greatly changing. Over the last 10 years the policy of the Dutch
      government has become less directive, market mechanisms are gaining weight and
      the demand for services by patients is changing. As a result of these changes
      hospitals formulate their strategic goals in terms of improvement of quality of
      care and efficacy. A basic assumption in this article is that quality of care is
      to be gained by collaborative practice between physicians and nurses. A necessary
      condition for this is that there is a correspondence in role concepts and
      expectancies of physicians and nurses in hospitals. The object of this research
      is to describe the role concepts and role expectations of nurses, physicians and
      patients in two Dutch hospitals. In general, the research revealed considerable
      differences between role behaviour and role concepts among nurses. In the long
      run these differences may not be favourable for good understanding between them
      and physicians, or for their own job satisfaction. This may also have negative
      consequences for collaboration between nurses and physicians and, finally, for
      the quality of care and cure within the ward. There is a need for discussion of
      the role concepts of nurses in relation to their actual regular tasks in order to
      resolve this. A second discrepancy exists between the role behaviour of
      physicians and the expectations of nurses about this behaviour. This may also
      lead to a lower job satisfaction for nurses. Taking into account the fact that
      patients are satisfied with the way physicians and nurses pay attention to most
      aspects of care and cure, a discussion between physicians and nurses could be
      recommended. The aim is revising either the role behaviour of physicians,
      especially as regards their attention to the psycho-social needs of patients, or
      the expectations of nurses, or both.

PMID- 9257406
TI  - Prevention of infectious disease transmission in sports.
AB  - A variety of infectious diseases can be transmitted during competitive sports.
      Modes of transmission in athletic settings include person-to-person contact,
      common-source exposures and airborne/droplet spread. This paper reviews the most
      commonly reported infectious diseases among athletes and discusses the potential
      for transmission of bloodborne diseases in sports. Guidelines are provided
      regarding measures to prevent transmission of infectious diseases in athletic
      settings, including hygiene and infection control practices, vaccination, and
      education of officials, coaches, trainers and sports participants.

PMID- 9257407
TI  - Beta-endorphin response to exercise. An update.
AB  - beta-Endorphin, a 31-amino-acid peptide, is primarily synthesised in the anterior
      pituitary gland and cleaved from pro-opiomelanocortin, its larger precursor
      molecule. beta-Endorphin can be released into the circulation from the pituitary
      gland or can project into areas of the brain through nerve fibres. Exercise of
      sufficient intensity and duration has been demonstrated to increase circulating
      beta-endorphin levels. Previous reviews have presented the background of opioids
      and exercise and discussed the changes in beta-endorphin levels in response to
      aerobic and anaerobic exercise. The present review is to update the response of
      beta-endorphin to exercise. This review suggests that exercise-induced beta
      endorphin alterations are related to type of exercise and special populations
      tested, and may differ in individuals with health problems. Additionally, some of
      the possible mechanisms which may induce beta-endorphin changes in the
      circulation include analgesia, lactate or base excess, and metabolic factors.
      Based on the type of exercise, different mechanisms may be involved in the
      regulation of beta-endorphin release during exercise.

PMID- 9257410
TI  - Effects of diet- and exercise-induced weight loss on visceral adipose tissue in
      men and women.
AB  - The effects of diet- and exercise-induced weight loss on visceral adipose tissue
      (VAT) distribution in both men and women have been reviewed. In general, current
      knowledge is based on studies that have assessed the influence of diet alone on
      VAT in obese women. For every kilogram of diet-induced weight loss, the
      corresponding reduction in VAT expressed in absolute terms is approximately 3 to
      4 cm2, and in relative terms is approximately 2 to 3%. Thus, a diet-induced
      weight loss of approximately 12 kg corresponds to a 30 to 35% reduction in VAT.
      Two studies that consider the effects of exercise per se on VAT report
      conflicting results. There appears to be a resistance to VAT reduction in obese
      women, whereas exercise-induced weight loss is associated with significant
      reductions in VAT in men. It was also reported that in obese men, reductions in
      VAT induced by the combination of diet and exercise are not different from those
      observed in response to diet alone. It is unclear whether the results of these
      studies reflect a biological truth or are confounded by methodological problems
      associated with the control of energy intake and expenditure in free-living
      patients. Evidence suggests that changes in waist circumference and sagittal
      diameter are well correlated with corresponding changes in VAT. A 1 cm reduction
      in waist circumference corresponds to a 5 cm2 (4%) reduction in VAT area at the
      L3 level. Data on the separate effects of diet- and exercise-induced weight loss
      on VAT from well controlled studies are required to advance current knowledge
      with respect to the effects of diet and exercise on the adipose tissue depot that
      conveys the greatest health risk.

PMID- 9257409
TI  - Fluid balance in team sports. Guidelines for optimal practices.
AB  - Team sports require players to perform multiple work bouts at near maximal
      effort, punctuated with intervals of low intensity exercise or rest for the
      duration of a game. Such activity patterns are associated with a significant loss
      of body water which has a negative impact on physical and mental performance, as
      well as temperature regulation. There are a number of ways in which sweat losses
      incurred during team sports differ from those measured during prolonged,
      continuous exercise. Firstly, the work rate in team sports is intermittent,
      largely unpredictable and random in nature. Second, analyses of various team
      sports reveal that such games are characterised by a high degree of inter and
      intra-individual variability in work rates between players from the same sport.
      Finally, team players are less able to anticipate sweat losses than athletes
      competing in events which involve prolonged, continuous, moderate intensity
      exercise. Yet, compared with most endurance events, many team sports offer
      frequent opportunities to ingest adequate volumes of fluid and thus prevent
      exercise-induced hypohydration. The present review details the findings of modern
      studies which have determined body water losses and fluid intake practices of
      athletes from a variety of team sports. Special considerations which influence
      sweat loss and fluid intake that are unique to team sports are discussed, and
      guidelines for sound hydration strategies during training and competition are
      provided.

PMID- 9257411
TI  - Common injuries in volleyball. Mechanisms of injury, prevention and
      rehabilitation.
AB  - Volleyball has become an extremely popular participation sport worldwide.
      Fortunately, the incidence of serious injury is relatively low. The sport
      specific activity most commonly associated with injury is blocking. Ankle sprains
      are the most common acute injury. Recurrent sprains may be less likely to occur
      if an ankle orthosis is worn. Patellar tendinitis represents the most common
      overuse injury, although shoulder tendinitis secondary to the overhead activities
      of spiking and serving is also commonly seen. An unusual shoulder injury
      involving the distal branch of the suprascapular nerve which innervates the
      infraspinatus muscle has been increasingly described in volleyball players in
      recent years. Hand injuries, usually occurring while blocking, are the next most
      common group of injuries. Fortunately, severe knee ligament injuries are rare in
      volleyball. However, anterior crutiate ligament injury is more likely to occur in
      female players. Many of these injuries may be preventable with close attention to
      technique in sport-specific skills and some fairly simple preventive
      interventions.

PMID- 9257408
TI  - Exercise recommendations for individuals with cystic fibrosis.
AB  - The role of exercise in the treatment of cystic fibrosis has received increasing
      attention over the past 15 to 20 years. As a group, physical fitness is reduced
      for people with cystic fibrosis, although tremendous individual variability
      exists. Limitations in exercise performance appear related to the extent of lung
      disease and compromised nutritional status. Exercise testing with subsequent
      development of individualised exercise programmes offers this unique population
      an opportunity to attain the well-recognised benefits of exercise.

PMID- 9257412
TI  - Modelling prevalence of a condition: chronic graft-versus-host disease after bone
      marrow transplantation.
AB  - A variety of estimators have been proposed for modelling how the proportion of
      patients with a transient condition varies over time. In this paper we compare
      these estimators qualitatively and quantitatively and introduce a new estimator
      based on a generalized additive model (GAM). The assumptions on which the various
      estimators are based are discussed. Using simulations we compare their
      performances and investigate their robustness to departures from the assumptions.
      The GAM estimator is the only one which can incorporate covariate information.
      Even when estimating a single prevalence function without any covariate
      information the GAM estimator is seen to be preferable as long as the censoring
      mechanism is random censoring. The GAM prevalence estimator is applied to data on
      chronic graft-versus-host disease following bone marrow transplantation.

PMID- 9257413
TI  - Frailty modelling for the excess hazard.
AB  - Long-term excess hazards for cancer survival sometimes tend to zero or become
      negative even though we expect them to be positive. This may be explained by
      selection at diagnosis; individuals with certain cancers may have an increased
      risk of dying of other diseases in general. Then comparing with population
      mortality rates is not correct. Alternatively, we may have a continuous selection
      of the most robust individuals after diagnosis. When there are unobserved
      heterogeneity, and those with highest risk of dying of cancer also have the
      highest risk of dying of other diseases, this will cause selection after
      diagnosis. This may be modelled by multivariate frailty variables, and a
      corrected excess hazard may be estimated. In two examples, these corrected excess
      hazards give a better estimate when comparing to the cause-specific cancer
      mortality. Actually, this study questions the usefulness of long-term excess
      hazard rates.

PMID- 9257414
TI  - Mixed models for bivariate response repeated measures data using Gibbs sampling.
AB  - Repeated measures data are frequently incomplete, unbalanced and correlated.
      There has been a great deal of recent interest in mixed effects models for
      analysing such data. In this paper, we develop bivariate response mixed effects
      models that are a generalization of linear mixed effects models for a single
      response variable. We describe their estimation procedures using a Markov chain
      Monte Carlo method, the Gibbs sampler. We illustrate the methods with analyses of
      intravenous vitamin D3 administration for secondary hyperparathyroidism in
      hemodialysis patients. In these data there were two response variables on each
      individual (PTH and calcium level). This study also suffered from attrition, like
      many longitudinal studies. While, considering the study design, it was reasonable
      to assume the drop-out mechanism for the calcium (Ca) level to be 'missing at
      random', the drop-out mechanism for the PTH level was likely to be non-ignorable.
      We found that the posterior treatment effects for the PTH level by the single
      response model were underestimated compared with those obtained by the bivariate
      response model, while there were little differences in the posterior features for
      the Ca level under both models.

PMID- 9257415
TI  - Maternal smoking during pregnancy and birth outcomes with weight gain adjustments
      via varying-coefficient models.
AB  - There is considerable interest in the impact of maternal exposures during
      pregnancy on birth outcomes. Clearly, exposures associated with poor birth
      outcomes need modification or avoidance. However, arriving at such estimates of
      association is made challenging by a number of features characteristic of the
      relevant data. First, exposures may be time varying (for example, cigarette and
      alcohol consumption) so that, to relate them to birth outcomes, one needs to
      model them and then extract derived parameters. Secondly, there are likely to be
      unequal numbers and spacings of exposure determinations during pregnancy.
      Thirdly, one needs to account for a variety of additional covariates. Finally,
      the variability and non-linearities inherent in birth outcomes mandate flexible
      modelling approaches. Here we use data from a cohort of East Boston mothers to
      assess the impact of smoking during pregnancy on birth weights. We emphasize
      modelling of, and then adjusting for, maternal weight gain during pregnancy and a
      proxy measure for pre-pregnancy weight, so as to obtain better estimates of the
      smoking effect. Throughout, our analysis is guided by appropriate graphics. The
      adjustment features an interesting application of varying-coefficient models.
      Results indicate that smoking related deficits in birth weights depend on the
      mode of adjustment, and that previously observed deficits of approximately 200 g
      are best recaptured with use of varying-coefficient models.

PMID- 9257416
TI  - Data-dependent interval partition of naturally ordered individuals by complete
      cluster analysis in epidemiological and cardiac data processing.
AB  - Cluster analysis cannot usually examine every possible clustering. However, some
      external constraint may reduce the number of clusterings to a practical amount.
      In this paper, we consider naturally ordered individuals and calculate the number
      of interval partitions among them, if a minimal width for each interval is
      demanded. Two examples illustrate the application of the method. We first
      determine optimal information preserving age intervals due to the frequencies of
      some diseases. In the second example, we find a subinterval of the
      intraventricular blood pressure curve suitable to determine the time constant of
      heart relaxation.

PMID- 9257417
TI  - Comparison of parametric and non-parametric survival methods using simulated
      clinical data.
AB  - We derived three parametric survival models (the log-normal, log logit, and
      Weibull) from the clinical data of chemotherapy trials for stage II breast
      cancer. We then used these models to generate simulated survival data, which we
      analysed using both parametric (log-normal) and non-parametric (logrank, Gray
      Tsiatis and Laska-Meisner) methods. With limited follow-up (5 years), the non
      parametric tests had greater power than the log-normal model. This advantage
      diminished, however, with extended follow-up (15 years). Furthermore, only the
      log-normal model could distinguish reliably a survival advantage due to an
      increase in cured fraction from an advantage due to an increase in time to
      failure.

PMID- 9257418
TI  - Test for qualitative interaction of clinical significance.
AB  - We generalize the problem of detecting qualitative interaction between treatments
      and subsets in a two treatment clinical trial to the more practical problem of
      detecting a qualitative interaction greater than a non-negative value d,
      corresponding to the minimal treatment difference of clinical significance. We
      develop a test based on simultaneous confidence intervals for the generalized
      problem under the assumption of normality. The proposed test is easy to
      implement, either by hand calculation or through the use of virtually any
      existing statistical software. We derive explicit power function for the proposed
      test and give examples to illustrate the procedures.

PMID- 9257419
TI  - Facilitated analysis of data on drug regimen compliance.
AB  - Drug actions depend on dose and intervals between doses, in ways that are drug
      specific and sometimes complex, complicating the use of drug dosing histories as
      an explanatory variable in the analysis of clinical trials. We describe a spread
      sheet method for conveniently displaying patients' drug dosing histories, to
      facilitate identification of dosing correlates of clinically important events.

PMID- 9257420
TI  - Orphan topics in supportive care: how about xerostomia?

PMID- 9257421
TI  - Supportive and palliative care at the University Hospital Lausanne.
AB  - The development of supportive and palliative care services within the Canton of
      Vaud in Switzerland is traced, and the current situation and future plans are
      outlined.

PMID- 9257424
TI  - Radiation-induced xerostomia: pathophysiology, clinical course and supportive
      treatment.
AB  - Xerostomia, or oral dryness, is one of the most common complaints experienced by
      patients who have had radiotherapy of the oral cavity and neck region. The
      hallmarks of radiation-induced damage are acinar atrophy and chronic inflammation
      of the salivary glands. The early response, resulting in atrophy of the secretory
      cells without inflammation might be due to radiation-induced apoptosis. In
      contrast, the late response with inflammation could be a result of radiation
      induced necrosis. The subjective complaint of a dry mouth appears to be poorly
      correlated with objective findings of salivary gland dysfunction. Xerostomia,
      with secondary symptoms of increased dental caries, difficulty in chewing,
      swallowing and speaking, and an increased incidence of oral candidiasis, can have
      a significant effect on the quality of life. At present there is no causal
      treatment for radiation-induced xerostomia. Temporary symptomatic relief can be
      offered by moistening agents and saliva substitutes, and is the only option for
      patients without residual salivary function. In patients with residual salivary
      function, oral administration of pilocarpine 5-10 mg three times a day is
      effective in increasing salivary flow and improving the symptoms of xerostomia,
      and this therapy should be considered as the treatment of choice. Effectiveness
      of sialogogue treatment requires residual salivary function, which emphasizes the
      potential benefit from sparing normal tissue during irradiation. The hypothesis
      concerning the existence of early apoptotic and late necrotic effects of
      irradiation on the salivary glands theoretically offers a way of achieving this
      goal.

PMID- 9257423
TI  - Medical futility and appropriate medical care in patients whose death is thought
      to be imminent.
AB  - Often it is very difficult to make decisions involving the termination of
      aggressive cancer care in the case of patients who are no longer benefiting.
      Among these patients, our ability to "do everything possible" to continue life is
      in conflict with "doing the right thing"; the greatest benefit to these patients
      derives from delivering excellent supportive care and assisting them in
      understanding and accepting end-of-life issues. Furthermore, in a cost-conscious
      environment with limited resources, all patients and, indeed, all of society,
      benefit when aggressive and often costly cancer care is limited to those patients
      who are likely to benefit. However, these issues are complex, blending treatment
      science and ethics, and thus, the physician frequently has no objective reference
      point on which to base the decisions. This paper integrates the principles of
      ethics (respect for autonomy, beneficence, nonmaleficence, and justice) and three
      difficult issues encountered by physicians in clinical decision-making in
      terminal cancer patients in the American healthcare system. These issues include:
      medical futility and appropriate care, applications of outcomes research in
      clinical decision-making, and impact of cost, particularly in a managed care
      environment, on treatment choice. These topics are illustrated with reference to
      patients presenting to our emergency center with stage IV lung cancer and
      dyspnea, and the application of an outcomes model under development to predict
      imminent death in these patients is discussed. Outcomes models may provide
      patients, their families, and their physicians with objective data on which to
      base end-of-life decision-making. Minimizing aggressive treatment of terminally
      ill patients may provide better life quality and will reduce costs during the
      patients' end of life. Ethics plays a crucial role in integrating medical
      science, patient choice, and cost in making appropriate decisions.

PMID- 9257422
TI  - Clinical and methodological issues in antiemetic therapy: a worldwide survey of
      experts' opinions. Multinational Association of Supportive Care in Cancer.
AB  - During the 1995 Multinational Association of Supportive Care in Cancer (MASCC)
      Congress, a consensus conference was planned by the Subcommittee for Antiemetics.
      To define the topics to be discussed, a questionnaire containing both clinical
      and methodological issues was sent to 118 experts in 31 countries. The
      questionnaire contained 33 items on clinical and 19 items on methodological
      issues, and each response was rated on a 4-level categorical scale. The clinical
      issues were evaluated for interest, that is clinical importance, and feasibility,
      that is availability of sufficient data to make them suitable topics for the
      consensus conference. About 60% of questionnaires were returned, with a small
      number of missing responses. The responses to the items of clinical interest
      showed that about two-thirds of the issues identified by the Subcommittee were
      found by the experts to be of at least high interest, but often the availability
      of data was found to be insufficient for their discussion. Prevention of acute
      emesis induced by cisplatin and by moderately emetogenic chemotherapy and the
      optimal intravenous dose and schedule of the 5-HT3 receptor antagonists were the
      items with the highest interest and feasibility. The issues in the methodological
      section were also mostly found to be of at least high interest. The distinction
      between acute and delayed emesis, the evaluation of the persistence of antiemetic
      efficacy in subsequent cycles of chemotherapy and the statistical analysis of
      delayed emesis were the methodological issues in which the highest interest was
      recorded. Data collected will be used to define the main topics to be discussed
      during the planned consensus conference.

PMID- 9257425
TI  - Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM
      CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving
      myelosuppressive chemotherapy.
AB  - A prospective, randomized, double-blind, multicenter study in cancer patients
      receiving myelosuppressive chemotherapy was undertaken to evaluate and compare
      the tolerability of sargramostim (yeast-derived recombinant human granulocyte
      macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived
      recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the
      prophylaxis or treatment of chemotherapy-induced neutropenia. In all, 137
      evaluable patients received sargramostim (300 micrograms; 193 mg/m2) or
      filgrastim (481 mg; 7 mg/kg) once daily by self-administered s.c. injection,
      usually beginning within 48 h after completion of chemotherapy. With the
      exception of a slightly higher incidence of grade 1 fever (< 38.1 degrees C) with
      sargramostim, there were no statistically significant differences in the
      incidence or severity of local or systemic adverse events possibly related to the
      growth factors. Although the study was not designed to evaluate efficacy
      directly, there also were no statistically significant differences between
      treatment groups in total days of growth factor therapy, days of hospitalization,
      or days of i.v. antibiotic therapy during the treatment period. Both sargramostim
      and filgrastim were comparably well tolerated when given by s.c. injection in
      this group of patients, and no clinically significant differences between the
      growth factors were demonstrated.

PMID- 9257427
TI  - Effect of postchemotherapy nausea and vomiting on health-related quality of life.
      The Quality of Life and Symptom Control Committees of the National Cancer
      Institute of Canada Clinical Trials Group.
AB  - The purpose was to measure the effects of postchemotherapy nausea and vomiting
      (PCNV) on health-related quality of life (HQL) in patients receiving either
      moderately or highly emetogenic chemotherapy. The study sample consisted of 832
      chemotherapy-naive patients with cancer who received either moderately or highly
      emetogenic chemotherapy as part of multicenter trials of new antiemetics. The
      patients completed the self-report European Organization for Research and Cancer
      (EORTC) core Quality of Life Questionnaire (QLQ-C30) before chemotherapy
      (baseline) and 1 week (day 8) and 2-4 weeks after chemotherapy. They also
      completed a self-report nausea and vomiting (NV) diary for 5-7 days after
      chemotherapy. To determine the effects of PCNV on HQL, the change in scores
      between the baseline and day 8 HQL assessments was calculated for each domain and
      symptom in the QLQ-C30 and compared in four subgroups of patients: those with
      both nausea and vomiting, those with nausea but no vomiting, those with no nausea
      but with vomiting, and those with neither nausea nor vomiting. The group with
      both nausea and vomiting showed statistically significantly worse physical,
      cognitive and social functioning, global quality of life, fatigue, anorexia,
      insomnia and dyspnea as compared to the group with neither nausea nor vomiting
      (0.0001 < P < 0.05). Patients with only nausea but no vomiting tended to have
      less worsening in functioning and symptoms than those having both nausea and
      vomiting. Increased severity of vomiting (> 2 episodes) was associated with
      worsening of only global quality of life and anorexia as compared with 1-2
      episodes of vomiting (0.0001 < P < 0.01). By 2-4 weeks after chemotherapy all HQL
      scores had either returned to their baseline levels or were better than baseline.
      PCNV adversely affects several quality-of-life domains, but patients with only
      nausea experience less disruption than do those with both nausea and vomiting.
      Patients with 1-2 episodes of vomiting experience almost the same degree of
      disruption of HQL as do patients with more than 2 episodes of vomiting.

PMID- 9257426
TI  - Factors influencing haematological recovery after allogeneic bone marrow
      transplantation in leukaemia patients treated with methotrexate-containing GVHD
      prophylaxis. A single-centre experience.
AB  - In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL,
      15 CML), the factors influencing haematological recovery after allogeneic bone
      marrow transplantation (alloBMT) were analysed retrospectively to identify the
      optimal conditions required for rapid haematological recovery after alloBMT. All
      patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The
      mean number of days required to achieve a neutrophil count > or = 0.5 x 10(9)/l
      after alloBMT was 17 (range 9-27), 19 patients (28.8%) had rapid neutrophil
      recovery within 15 days after alloBMT. Haematological recovery was more rapid in
      the 38 patients without GVHD or with only grade I GVHD. Also, 50% and 40% of
      patients receiving 10 (n = 18) or 5 (n = 20) micrograms/kg G-CSF per day,
      respectively, had rapid neutrophil recovery within 15 days after alloBMT, as
      against only 7.1% of patients not receiving G-CSF after the transplant (n = 28);
      P < 0.001. The neutrophil recovery was similar in patients receiving either fresh
      or cryopreserved allografts and either a TBI-containing or a busulfan-containing
      conditioning regimen. A significant correlation was found between the neutrophil
      recovery and either the MNCs or CFU-GM contents of the allografts. The mean
      number of days required for neutrophil recovery was only 16 (range 9-24) in
      patients receiving allografts containing > 1 x 10(5) CFU-GM/kg (n = 28), as
      against 19 (range 13-27) in patients receiving allografts containing < or = 1 x
      10(5) CFU-GM/kg (n = 35). Three patients receiving allografts containing < 0.5 x
      10(5) CFU-GM/kg had primary neutrophil engraftment failure. The mean number of
      days required to achieve a platelet count > or = 20 x 10(9)/l was 21 (range 11
      50), and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT.
      The platelet recovery after alloBMT was not affected by the type of leukaemia,
      conditioning regimen, or G-CSF administration. The mean number of days required
      for platelet recovery after alloBMT was 20 in patients receiving allografts
      containing > 1.0 x 10(5) BFU-E/kg (n = 35), as against 23 days in patients
      receiving allografts containing < or = 1.0 x 10(5) BFU-E/kg (n = 24). Seven
      patients receiving allografts containing < 0.5 x 10(5) BFU-E/kg had primary
      platelet engraftment failure. The present study has identified the high number of
      progenitor cells in the allografts infused and the daily administration of G-CSF
      posttransplant as the optimal combination for rapid neutrophil recovery after
      alloBMT. More significantly, the number of BFU-E in allografts was the most
      significant determining factor in platelet recovery after alloBMT. The
      development of GVHD of grade II or more during the first weeks after alloBMT was
      associated with slower haematological recovery, a longer period of fever during
      neutropenia and longer hospitalization.

PMID- 9257428
TI  - Evaluation of factors influencing 5-fluorouracil-induced diarrhea in colorectal
      cancer patients. An Italian Group for the Study of Digestive Tract Cancer
      (GISCAD) study.
AB  - Diarrhea is one of the dose-limiting toxicities for administration of
      fluorouracil (5FU) in patients with colorectal cancer and can result in severe
      morbidity and mortality. No well-defined prognostic factors influencing 5FU
      associated diarrhea have been identified, which means its occurrence is
      unforeseeable. The aim of this study was to check whether any characteristics
      related to patients or chemotherapy could allow the identification of subsets of
      patients at higher risk of developing diarrhea while receiving a regimen
      containing 5FU. A logistic regression analysis was performed with age, sex, site
      of primary tumor, presence of primary tumor, presence of colostomy, time since
      surgery, number of courses of chemotherapy, diarrhea in previous courses, season
      of treatment, and chemotherapeutic regimens used as model parameters to predict
      occurrence of diarrhea in 258 colorectal cancer patients receiving a 5FU
      containing regimen. Presence of primary tumor (P = 0.004), previous episodes of
      chemotherapy-related diarrhea (P = 0.00005) and summer season (P = 0.014) were
      found to be significant risk factors for developing diarrhea. The other variables
      examined, such as age, sex, chemotherapeutic regimen, site of primary tumor,
      presence of colostomy, and time since surgery, were not significantly correlated
      to diarrhea. Chemotherapeutic regimen was the only parameter that allowed
      prediction of the severity of diarrhea: 5FU/6S-leucovorin/interferon caused more
      severe diarrhea, followed by 5FU/leucovorin weekly. Although the analysis of
      these clinical features does not seem to allow the definition of a well-defined
      subset of colorectal cancer patients at higher risk of 5FU-induced diarrhea, it
      can be recommended that patients with primary tumor, or who have experienced
      diarrhea in earlier courses of chemotherapy or are receiving treatment in summer
      should be carefully monitored, especially in the first cycles.

PMID- 9257429
TI  - Adjuvant chemotherapy in Dukes' B and C colorectal cancer has only a minor
      influence on psychological distress.
AB  - The object of this cross-sectional study on psychological distress was to reveal
      such distress among patients treated for colorectal cancer (CRC). Between 1993
      and 1996, 95 patients in northern Norway were included in the national study
      randomising Dukes' B and C CRC patients between adjuvant chemotherapy (ACT: 5
      fluorouracil and levamisole) or follow-up following radical surgery. In April
      1996, all 82 survivors were mailed the Impact-of-Event Scale (IES), to which 64
      patients responded (78%). Less than one-third of the patients reported a moderate
      to high level of psychological distress. Scores predicting significant stress
      response syndrome were revealed in 14% of the patients. The mean score on the
      intrusion and avoidance scales were 6.1 and 7.7, respectively. Such variables as
      age, sex, tumour location (rectum/colon), Dukes' stage B/C and time of follow up
      did not significantly influence the scores. Patients receiving ACT reported only
      a slightly raised level on the intrusion (6.97 vs 5.17) and avoidance (8.48 vs
      6.80) scales. This study indicates that ACT in CRC Dukes' B and C is not a
      stressful happening. All advantages in survival achieved by ACT have to be
      weighed against the "cost" in terms of physical and psychological side effects.
      This study indicates the weighting in terms of psychological distress may be
      minimal.

PMID- 9257430
TI  - Living with mastectomy and breast conservation treatment: who suffers more?
AB  - Sixty-five patients who underwent modified radical mastectomy were compared with
      55 breast conservation patients, all of whom were in stage I, II or III of breast
      cancer and were under treatment at an oncology clinic in northern Israel. The
      main findings indicate no differences between the groups in physical,
      psychosocial, marital or medical interaction, according to the CARE scale. These
      findings reflect the results of similar comparative studies conducted during the
      1980s and 1990s as documented in the literature. Sexual interaction showed
      statistical differences favoring the women who had undergone mastectomies.

PMID- 9257431
TI  - Treatment of pain in chronic bowel subobstruction with self-administration of
      methadone.
AB  - Chronic treatment with opioids in cancer patients with chronic intestinal
      obstruction is hazardous, as uncontrolled constipation may result in definitive
      bowel obstruction. Intermittent use of opioids adjusted for fluctuating pain
      levels may enable patients to take the lowest opioid doses that will have
      sufficient effect, with a consequently lower risk of intestinal side effects.
      Methadone has many pharmacokinetic characteristics that fit it for use in this
      clinical situation. In two patients with recurrent episodes of bowel obstruction,
      methadone used at low doses and at flexible intervals regulated by the patients
      according to their pain level avoided the occurrence of new episodes of
      intestinal obstruction. Oral patient-controlled analgesia with methadone may be a
      simple, safe and cheap method of treating patients with pain associated with
      subtotal intestinal obstruction.

PMID- 9257432
TI  - Analysis of 553 episodes of monomicrobial bacteraemia in cancer patients: any
      association between risk factors and outcome to particular pathogen?
AB  - Relationships between aetiology, various risk factors (such as neutropenia,
      catheter insertion, endoscopy, therapy with corticosteroids, therapeutic use of
      antimicrobials, antibiotic prophylaxis, source of infection), symptomatology and
      outcome were studied in 553 monomicrobial bacteraemic episodes in cancer patients
      observed within 7 years at the National Cancer Institute of the Slovak Republic.
      The ratio of gram-positive to gram-negative bacteraemia was 1:1 (43.5% vs 43.8%),
      and yeasts caused 7.2% of monomicrobial episodes. The highest mortality was
      associated with Pseudomonas aeruginosa (19.2%), non-albicans Candida yeasts (25%)
      and Bacteroides fragilis (22.6%). Independent risk factors for particular
      pathogens were investigated by a computerized logistic regression model. The only
      independent risk factor for staphylococcal and enterococcal bacteraemia was
      vascular catheter insertion (OR = 1.95 and 2.05, CI = 95%, P = 0.035 and 0.044,
      respectively). However, there were no independent specific risk significant
      factors for viridans streptococcal bacteraemia and bacteraemia due to
      Enterobacteriaceae or Ps. aeruginosa. Neutropenia was found to be an independent
      predictor for development of Acinetobacter spp. bacteraemia (OR = 3.84, CI = 95%,
      P = 0.044). Prior therapy with third-generation cephalosporines was a predictive,
      independent risk factor for the development of fungaemia (OR = 1.99, CI = 95%, P
      = 0.028) but not of enterococcal bacteraemia. We also did not observe any
      association between prior therapy with imipenem and Stenotrophomonas maltophilia
      bacteraemias. Multivariate analysis confirmed that fungaemia may be independently
      associated with higher mortality than bacteraemia caused by Enterobacteriaceae
      and staphylococci. However, the mortality of fungaemia was statistically no
      different from that of Ps. aeruginosa, Stenotrophomonas spp. and viridans
      streptococci bacteraemias.

PMID- 9257433
TI  - Postoperative bacteremia in cancer patients with solid tumors undergoing surgery:
      risk factors, etiology and outcome in 276 patients.

PMID- 9257434
TI  - Use of a live chlamydial vaccine to prevent ovine enzootic abortion.
AB  - A lyophilised chlamydial vaccine was prepared from the 1B temperature-sensitive
      strain of ovine Chlamydia psittaci. Ewes inoculated with a low titre of the live
      vaccine four weeks before artificial insemination were challenged on day 70 of
      gestation with five UK field isolates of C psittaci, including strains A22 and
      S26/3 previously incorporated into a commercial inactivated vaccine. There was a
      significantly lower chlamydial abortion rate after challenge in the vaccinated
      group (7.1 per cent) than in the unvaccinated group (80 per cent). All the lambs
      born to the vaccinated ewes were viable and of good quality. The vaccine also
      reduced the number of infected ewes in the group and the severity of the
      infection. The compatibility of the chlamydial vaccine and a toxoplasma vaccine
      was also tested. The abortion rate of ewes vaccinated with the two vaccines at
      separate injection sites (16 per cent) was less than that of ewes vaccinated with
      both vaccines at one site (32 per cent).

PMID- 9257435
TI  - Body condition score, health, yield and fertility in diary cows.
AB  - The effects of body condition score at drying off and after calving and the rate
      of loss of body condition score during the dry period on the performance of 2162
      cows in eight commercial Israeli Holstein herds were evaluated. The relationships
      between health, fertility and yield and body condition score were examined by
      using multiple logistic regressions for measurements with only two outcomes and
      general linear models for the continuous variables. Herds, parity, season, length
      of dry period, postparturient diseases, twinning, stillbirth, induction of
      calving and high somatic cell counts were used as confounding and other exposure
      variables. Multiparous cows that were underconditioned at calving were culled and
      exhibited more postparturient uterine diseases. The risk of retained placenta was
      greater for cows that were underconditioned at drying off, whereas cows that lost
      more body condition during the dry period suffered more from both retained
      placenta and metritis; the two effects being independent of each other. An
      apparent increase in the risk of ketosis associated with over-conditioning at
      calving could be partly attributed to long dry periods. Cows with a higher
      condition score at calving were less prone to anoestrus but did not conceive more
      successfully to first service. A reduction of six open days in primiparous cows
      was estimated for each additional unit of body condition score at calving.
      Multiparous cows that lost more body condition during the dry period suffered
      more from inactive ovaries and were more likely to be open 150 days after calving
      in the next lactation. Cows calving in a higher body condition score produced
      more milk, fat and protein in the first 90 days of lactation, the effect being
      most pronounced on milk fat content.

PMID- 9257436
TI  - Aggressive behaviour in English cocker spaniels and the personality of their
      owners.
AB  - The aim of the study was to determine whether there is an association between the
      personality of the owners of English cocker spaniels and the expression of
      aggressive behaviour by their dogs. Two-hundred-and-eighty-five owners of
      purebred English cocker spaniels completed the Catell 16 Personality
      Questionnaire. One-hundred-and-twenty-eight of them owned 153 dogs previously
      classified as being 'low' in terms of aggressiveness and 157 owned 172 dogs
      classified as being 'high' in terms of aggressiveness. Both groups of owners were
      similar in terms of a variety of demographic variables, including the number of
      adults and children in the household, the type of house and the sex of the owner.
      The dogs in both groups were similar in age, age when acquired and sex ratio.
      Analyses of the data using unpaired t-tests revealed that the owners of high
      aggression dogs were significantly more likely to be tense (P < 0.001),
      emotionally less stable (P < 0.01), shy (P < 0.01) and undisciplined (P < 0.05)
      than owners of low aggression dogs.

PMID- 9257437
TI  - Simplified gall bladder cannulation in cattle.

PMID- 9257438
TI  - A case of equine cholangiocarcinoma displaying aberrant expression of p53
      protein.

PMID- 9257439
TI  - Rabies and quarantine: report of the BVA working group.

PMID- 9257440
TI  - Virulent foot rot in sheep.

PMID- 9257441
TI  - Exotics on the Internet.

PMID- 9257442
TI  - Clinical mastitis in dairy cows after 'blitz' therapy.

PMID- 9257443
TI  - Resistance of Escherichia coli growing as biofilms to disinfectants.
AB  - The bactericidal activity of various disinfectants (cationic or amphoteric
      surfactants, oxidizing agents, phenolic derivatives) was determined against
      Escherichia coli CIP 54127 obtained by culture on tryptic soy agar (in-suspension
      or on-germ-carrier test) or in the form of biofilms produced in a continuous
      culture system. The bacteria tested on germ-carriers or included in biofilms were
      more resistant than the same strain in suspension. The extent of the reduction in
      activity depended on the nature of the disinfectant. In the two cases, the
      greatest reduction was observed with benzalkonium chloride and hexadecyl
      trimethylammonium bromide, the agents with the lowest hydrophile-lipophile
      balance. The activity of the oxidizing agents (sodium hypochlorite, peracetic
      acid/H2O2) and alkyl trimethylammonium derivatives (C12 and C14) was somewhat
      reduced, while that of the phenolic derivatives (o-cresol, phenol) was either
      slightly attenuated or unaffected. The reduction in sensitivity was attributed to
      a reduced accessibility of the bacterial cells to the disinfectants, due to the
      fact that the former adhered to a support. Furthermore, the interfering action of
      the substances in contact with the bacteria (milk in the germ-carrier test and
      exopolymers in the biofilms) could play a role. The reduced sensitivity of the
      bacteria in the biofilms was not due to any alteration in the metabolic state of
      the bacteria (mostly in a quiescent state) since this resistance was lost after
      the mechanical resuspension of the cells before the contact with the
      disinfectants.

PMID- 9257444
TI  - The Brucellin skin test as a tool to discriminate false positive serological
      reactions in bovine brucellosis.
AB  - Three experiments were performed in order to assess the diagnostic value of the
      Brucellin allergic skin test (AST) in a brucellosis false positive serological
      reactions (FPSR) context. First, 1259 cattle from 20 Brucella-free herds in a
      FPSR area were tested twice with AST to estimate its specificity. Secondly, AST
      and serological tests (complement fixation test [CFT], tube agglutination test,
      dithiothreitol-microagglutination test and ELISA) sensitivities were evaluated on
      111 cattle positive to the Rose Bengal test (RBT) belonging to 15 Brucella
      infected herds. Thirdly, AST was used in a field trial to discriminate FPSR from
      true brucellosis reactions. AST specificity in non-vaccinated cattle was very
      high (99.83%; confidence interval 95% [CI95%]: 99.67-99.96%). Skin thickening 72
      h post-injection was significantly higher on vaccinated cattle (1.42 vs 0.15 mm).
      In this sub-population, AST specificity decreased significantly to 78% (CI95%: 68
      87%). Individual sensitivity of AST relative to Rose Bengal test was 64% (CI95%:
      54-72%), while all infected herds were AST positive (n = 15). When associated
      with CFT, it detected 95% (CI95%: 90-98%) of the infected cattle. These results
      were consistent with the field trial. In a FPSR context, AST was more specific
      than RBT or CFT. Therefore, this test could be used at herd level as a
      confirmation test, on cattle non vaccinated against brucellosis.

PMID- 9257445
TI  - False positive serological reactions in bovine brucellosis: evidence of the role
      of Yersinia enterocolitica serotype O:9 in a field trial.
AB  - To investigate the epidemiology of false positive serological reactions (FPSR) in
      bovine brucellosis, 1259 bovines from 20 herds were sampled on three successive
      occasions during the winter of 1993-1994 in an area where the herd prevalence
      rate of FPSR was high. Serum samples were examined by classical brucellosis
      serological tests (Rose Bengal and complement fixation) and faeces were cultured
      for the presence of Yersinia enterocolitica O:9. Thirty-nine bovines expressed at
      least one positive serological reaction during the study. In the herds with FPSR
      during the 1993-1994 annual brucellosis surveillance campaign, the specificity of
      the brucellosis serological tests varied significantly from December to March
      (97.0% to 99.1%). Y enterocolitica O:9 was isolated from 42 bovines but only
      three of them showed a positive serological response during the study. Y
      enterocolitica O:9 isolation rates also decreased with time. Young animals and
      animals having demonstrated FPSR in the past had a greater risk of having a FPSR.
      Older animals, which rarely showed FPSR, could form a reservoir for Y
      enterocolitica O:9. While isolation of Y enterocolitica O:9 was not linked to
      presence of FPSR and conversely, the FPSR phenomenon should be considered, either
      at the herd level or at the individual level. This work reinforces the link, at
      least partial, between FPSR and infection by Y enterocolitica O:9.

PMID- 9257446
TI  - Safety of lysosubtilin per os in mice, rabbits and calves.
AB  - Lysosubtilin is a broad-spectrum preparation of lytic enzymes from Bacillus
      subtilis designed for veterinary medicine as an alternative to common
      antibiotics. The safety of lysosubtilin was studied in acute and subchronic
      toxicity tests in mice, rabbits, and calves. No sign of toxicosis was observed
      when lysosubtilin was administered as a single dose per os to white mice in doses
      reaching 2 x 10(6) U/kg of weight. Subcutaneous LD50 of lysosubtilin in mice was
      equal to 5 x 10(5) U/kg of weight. In order to determine subchronic toxicity in
      mice and rabbits the doses of lysosubtilin used in veterinary practice (2 x 10(4)
      U/kg of weight) were increased up to ten times (2, 8, 20.10(4) U/kg of weight)
      and when experimenting with calves they were increased up to two times (4.10(4)
      U/kg of weight) while extending the administration period by three times. In the
      three animal species, given in increased doses twice a day per os for 30 days,
      lysosubtilin did not cause any evident signs of clinical toxicosis. The blood and
      sera indices of rabbits and calves were within the normal range. In calves the
      changes were insignificant. The ANOVA test, however, revealed statistically
      significant differences in hemoglobin, WBC, protein, and glucose value changes
      between rabbit groups which were given different doses of lysosubtilin. A
      significant increase in daily weight gain (approximately 100 g, P < 0.001),
      influenced by lysosubtilin, was observed in calves. No deviations from the normal
      status were observed in the organs and tissues obtained during the post-mortem
      examination of rabbits and calves slaughtered 1 and 15 days after the end of
      lysosubtilin administration. Veterinary-sanitary examination of the slaughtered
      animals and laboratory tests of their meat showed normal commercial and sanitary
      qualities.

PMID- 9257447
TI  - Field trial of immunization with an experimental vaccine against Mediterranean
      theileriosis in Spain.
AB  - Vaccines against Mediterranean theileriosis have been developed in several
      countries where this disease is of economic concern. Until recently, tissue
      culture vaccines were a suitable method for immunizing cattle and they have been
      widely applied with success. In Spain, Mediterranean theileriosis is an obstacle
      to the improvement of dairy cattle productivity. No vaccines against this disease
      have been applied until recently. This report concerns the field trial of an
      available experimental tissue culture vaccine consisting of attenuated Theileria
      annulata schizont infected cells from an enzootic area of Spain. The vaccinated
      cattle developed a typical post-vaccination immunological response and were
      resistent to a field challenge. They showed no clinical signs of theileriosis
      while 50% of the control cattle showed typical signs of the disease and two of
      them died (12.5% of control cattle). This vaccine may be useful to protect cattle
      against Mediterranean theileriosis in enzootic areas of Spain.

PMID- 9257448
TI  - The effect of cotrimoxazole on experimental Cryptosporidium parvum infection in
      kids.
AB  - The prophylactic and therapeutic effects of the folic acid inhibitor
      cotrimoxazole (trimethoprim in combination with sulfamethoxazole) was tested in
      goat kids experimentally infected with Cryptosporidium parvum oocysts. Of the
      twenty-four 6-day-old kids inoculated with 6 x 10(6) oocysts of C parvum, ten
      kids were administered cotrimoxazole prophylactically at a dose 20 mg/kg per day
      of trimethoprim/100 mg/kg per day of sulfamethoxazole for 14 consecutive days
      beginning 1 day before infection. Six kids were therapeutically treated at the
      same dose of cotrimoxazole for 9 consecutive days beginning 5 days post
      infection, and eight kids served as untreated controls. Experimental C parvum
      infection caused a severe clinical disease with profuse watery diarrhea, oocysts
      shedding and intestinal lesions in all groups of kids. Total days and severity of
      diarrhea were similar for all groups of kids. However, the mean duration of
      oocysts shedding, mean number of cryptosporidia per ileal villus, and
      distribution of cryptosporidia in the intestine were increased in both groups of
      cotrimoxazole-treated kids. These findings indicate that cotrimoxazole failed to
      control cryptosporidiosis.

PMID- 9257449
TI  - Treatment of diabetes mellitus in dogs using isophane insulin penfills and the
      use of serum fructosamine assays to diagnose and monitor the disease.
AB  - The objectives of the study were to test the use of a prefilled insulin syringe
      (Insulatard Novolet, isophane insulin, 100 IU/mL) in treating diabetic dogs and
      to test the clinical usefulness of serum fructosamine measurements in diagnosing
      and monitoring diabetes mellitus in dogs. For this study 15 dogs from throughout
      Norway with newly diagnosed diabetes mellitus were included and treated over a
      period of 180 days. All 15 dogs showed pretreatment hyperglycaemia. Of the 13
      dogs tested, all showed elevated pretreatment serum fructosamine values. Within 2
      weeks, 3 of the 15 included dogs had dropped out of the study. In 8 of the 12
      remaining dogs, the clinical signs ceased within this period. Within a month,
      another dog was euthanised and one had died. Seven of the 10 remaining dogs were
      clinically normal. Three dogs had normal serum fructosamine concentrations, while
      in 6 dogs moderately or highly elevated serum fructosamine concentrations
      persisted. In one case serum fructosamine was not measured at this time. Increase
      in serum fructosamine concentration seemed to reflect hyperglycaemia and
      deteriorated clinical condition. Decrease in serum fructosamine concentration
      seemed to reflect improved glycaemic status and clinical condition. During the
      study period the owners did a total of approximately 3500 injections on their
      dogs. No reports of injection difficulties were received. This study documents
      that Insulatard Novolet is easy and safe to use in treating diabetic dogs and
      that serum fructosamine reflects long-term glucose concentrations in dogs. Serum
      fructosamine measurements provided a simple and easy way to diagnose persistent
      hyperglycaemia and monitor the treatment in diabetic patients.

PMID- 9257450
TI  - Recovery of Schistosoma japonicum from experimentally infected pigs by perfusion
      of liver and mesenteric veins.
AB  - An optimized procedure for perfusion of pigs infected with Schistosoma japonicum
      was developed. The technique involves insertion of a perfusion influx tube into
      the thoracic descending aorta, clamping vessels to parts of the body which did
      not need to be perfused (the kidneys, hind legs, etc.) and placing a collection
      tube directly into the portal vein. In addition, the clamping technique allows
      for separate perfusion of the liver and intestinal veins. The perfusion medium
      was a sodium citrate buffer (40 degrees C) to which the vasodilator sodium
      nitroprusside was added. Furthermore, an experiment was conducted to investigate
      if the perfusion efficiency, measured by total worm recovery, could be increased
      if praziquantel was administered prior to perfusion. Twelve pigs were each
      infected with 1000 S. japonicum cercariae and their schistosomes were collected
      11 weeks later by separate perfusion of the liver and intestinal veins. Six of
      these pigs were treated orally with praziquantel one hour before perfusion. In
      general, the vessels of the livers and intestines of all pigs were well perfused,
      judging by the resulting pale colour of the tissues. Worms from praziquantel
      treated pigs were collected within 5 min of perfusion as opposed to approximately
      20 min in the non-treated pigs. More worms were collected from the livers of the
      praziquantel treated pigs, indicating a hepatic shift of schistosomes from the
      intestinal mesenteries. However, comparable numbers of worms were retained in the
      mesenteric veins following perfusion in the 2 groups, indicating that manual
      recovery of schistosomes from the intestinal mesenteries is necessary in addition
      to perfusion for obtaining the total worm counts. Another experiment was
      conducted to determine if the intensity and/or duration of infection had an
      effect on the number of worms collected by the perfusion technique. Seventy-two
      pigs were allocated into 3 groups of 24 pigs each, which were infected with
      either 100, 500 or 2000 cercariae per pig. The 3 groups were further divided into
      4 subgroups of 6 pigs each which were perfused with our selective technique at 4,
      11, 17 or 24 weeks post infection, respectively. All of the pigs received an oral
      praziquantel treatment prior to perfusion. The results indicated that increasing
      intensities and/or duration of infection resulted in trapping of schistosomes in
      intravascular inflammatory reactions which made it more difficult to collect the
      adult schistosomes by perfusion.

PMID- 9257451
TI  - Occurrence of Gasterophilus intestinalis and some parasitic nematodes of horses
      in Sweden.
AB  - A survey was performed on the occurrence of some internal parasites in 461 horses
      (1-30 years old) slaughtered from October 1992 to September 1993 at the Linkoping
      abattoir in central Sweden. Macroscopical examination was carried out
      specifically for parasites of the tear ducts and conjunctival sacs of the eyes,
      and of selected parts of the alimentary tract and cardio-vascular system. The
      following parasites were found in selected parts of the large intestine:
      encapsulated cyathostome larvae (in 35.6% of the horses), and mature strongyle
      worms (17.4%); in the stomach: Gasterophilus intestinalis (12.3% during October
      June) and Habronema muscae (1.1%); and in the conjunctival sac: Thelazia
      lacrymalis (3.1%). Significantly more encapsulated cyathostome larvae were found
      during January to June than during other times of the year, and horses aged 1-5
      years harboured significantly more larvae than older horses. Severe damage to the
      cranial mesenteric artery and its main branches was noticed in 16 (6.1%) out of
      263 horses specifically examined. However, the 4th stage larva of Strongylus
      vulgaris was only recovered in 6 (2.3%) of the horses. Quantitative and
      qualitative faecal egg counts were done on 412 and 384 of the horses,
      respectively. Eggs of strongyles, Parascaris equorum and Strongyloides westeri
      were found in 78.1%, 1.9% and 0.2% of the faecal samples, respectively. Highest
      prevalence of strongyle eggs was found during July to September. Third stage
      larvae of the following nematodes were recovered from faecal cultures: subfamily
      Cyathostomum sensu lato (78.1%) Triodontophorus spp. (6.5%), Strongylus vulgaris
      (3.6%), Trichostrongylus axei (1.3%), while Gyalocephalus sp., Oesophagodontus
      sp., Poteriostomum sp. and Strongylus edentatus each comprised less than 0.5%.

PMID- 9257452
TI  - Rearing conditions and foot-pad dermatitis in Swedish turkey poults.
AB  - A method previously developed for classification of broiler foot health status
      was used in order to estimate the prevalence of foot-pad dermatitis in Swedish
      turkey poults. Data on foot health were collected from 53 commercial turkey
      flocks at slaughter. The producers were asked to fill in a questionnaire on
      rearing conditions and equipment for every flock. Lesions were very commonly
      observed, only 2% of the feet were classified as being without lesions, 78% had
      mild lesions (discoloration, erosions), and 20% had severe lesions (ulcers).
      There was a significant (p < 0.01) effect of litter material on the presence of
      severe foot-pad dermatitis, flocks reared on straw showing higher prevalence than
      flocks reared on wood shavings. There was also a significant (p < 0.001) effect
      of the type of water system, severe foot-pad dermatitis being more common in
      flocks reared in houses equipped with bell drinkers compared with flocks reared
      with small cups. The addition of extra litter during the rearing period resulted
      in significantly (p < 0.01) lower prevalence of lesions compared with flocks
      where no extra litter had been added.

PMID- 9257453
TI  - Nematode-trapping fungi in biological control of Dictyocaulus viviparus.
AB  - Larvae of the cattle lungworm Dictyocaulus viviparus were cultured in
      experimental units of 200 g cattle faeces placed in semi-transparent trays in the
      laboratory. In each of 4 experimental series using this experimental unit,
      chlamydospores (chl) of the nematode-trapping fungus Duddingtonia flagrans were
      admixed to half of the faecal cultures in a concentration of 50.000 chl/g. In all
      4 series there was a significant reduction in the development and subsequent
      release of infective lungworm larvae from faecal cultures containing
      chlamydospores. The average reduction in larval release, caused by fungal spores,
      was 86%.

PMID- 9257455
TI  - Haemophilus somnus--unlikely to be a causative microbiological agent in bovine
      clinical mastitis in Denmark.

PMID- 9257454
TI  - Comparison of ketosis, clinical mastitis, somatic cell count, and reproductive
      performance between free stall and tie stall barns in Norwegian dairy herds with
      automatic feeding.
AB  - Differences in ketosis and clinical mastitis rates, mean somatic cell counts
      (SCC) and reproductive performance scores (fertility status index = FS-index)
      between herds housed in free stall (n = 533) and tie stall (n = 59) barns were
      measured in relation to management and environmental factors in a retrospective
      cohort study of Norwegian dairy farms with automatic grain feeding systems. Herds
      with tie stalls were found to have a higher clinical mastitis rate, (61.6 cases
      per 100 cow-years versus 46.4 cases per 100 cow-years (p < 0.01)); a
      significantly higher proportion of herds with ketosis, (relative risk = 1.59, (p
      < 0.01)); and a lower mean fertility status index, (67.3 versus 82.8 (p < 0.01)).
      No significant difference in mean SCC was found between the 2 groups of dairies
      (p = 0.32). Large herds had higher Loge geometric mean SCC than small herds (p <
      0.01) and herds with high SCC had lower milk production than herds with low SCC
      (p < 0.01). Herds that scored "very good" on cow cleanliness had significantly
      lower adjusted mean SCC than herds with scores of "average" or "good" (p < 0.05).
      Herds in barns with a concrete floor had an adjusted mean number of cases of
      clinical mastitis of 51.4 per 100 cow-years, 14 per cent higher than herds in
      barns with rubber mats, litter bed or wood (45.2 cases per 100 cow-years) (p <
      0.05). Herds with high milk production level had higher FS-index than herds with
      low milk production (p < 0.01). Lower disease rates and the higher fertility
      status measured in the present study favor free stall herds over tie stall herds.

PMID- 9257456
TI  - CAEV infection does not affect prevalence of bacterial mastitis in goats.

PMID- 9257457
TI  - Occurrence of Pneumocystis carinii in canine distemper.

PMID- 9257459
TI  - The trigeminal system in man.

PMID- 9257458
TI  - The projections to the spinal cord of the rat during development: a timetable of
      descent.
AB  - In order to establish a timetable for the developmental descent of supraspinal
      descending projections in the rat, a retrograde neuronal tracer was injected into
      the spinal cord of rat fetuses and neonates both at different gestational ages
      and at different levels of the spinal cord. From the results of these experiments
      a position interval could be deduced for the leading descending fibers of each
      spinal-projecting nucleus at each age studied. The chronological series of
      position intervals of each supraspinal descending projection (the descent
      pattern) depicts the descent of its fiber front during development and allows for
      easy comparison between the various projections. According to these descent
      patterns the descent sequences of the various spinal-projecting nuclei were
      established. At E17 fibers from the lateral vestibular nucleus, the raphe magnus
      nucleus and the gigantocellular reticular nucleus were present in the lumbosacral
      spinal cord; their descent along the spinal cord thus occurs before this stage.
      At E18 fibers from the parafascicular prerubral nucleus, the interstitial nucleus
      of Cajal, the mesencephalic reticular nucleus, the caudal pontine reticular
      nucleus, the laterodorsal tegmental nucleus, the subcoerulean nucleus, the spinal
      vestibular nucleus, the interpolar spinal trigeminal nucleus, the raphe obscurus
      nucleus and the ventral medullary reticular nucleus arrived in the lumbosacral
      cord. At the same stage fibers from the oral and caudal spinal trigeminal nucleus
      reached their caudalmost extent in the spinal cord, respectively, the lower and
      upper thoracic cord. At E19 fibers from the oral pontine reticular nucleus, the
      parvocellular reticular nucleus, the ventral gigantocellular reticular nucleus
      and the ambiguous nucleus first appeared in the lumbosacral cord. At E20 fibers
      from Darkschewitsch's nucleus, the paralemniscal and parabrachial nuclei, cell
      group A5, the locus coeruleus, the gigantocellular reticular nucleus-alpha, the
      raphe pallidus nucleus, the paramedian reticular nucleus, and from the dorsal
      medullary reticular nucleus arrived in the lumbosacral cord. Last to arrive in
      the lumbar cord during the prenatal period, at E21, were fibers from the
      posterior commissural nucleus, the red nucleus, the Edinger-Westphal nucleus, the
      paragigantocellular reticular nucleus, the medial vestibular nucleus, Roller's
      nucleus, and the solitary nucleus. Fibers from the paraventricular hypothalamic
      nucleus and from the lateral hypothalamic area only arrived in the lumbosacral
      cord at P1, followed by fibers from the incertal nucleus at P4. A transient
      spinal projection from an unknown group of neurons located immediately lateral to
      and partly intermingled with the mesencephalic trigeminal nucleus arrived in the
      lumbosacral spinal cord at E18 and had disappeared at P1. This cell group, called
      Gr?, closely resembled the mesencephalic trigeminal nucleus (Me5). Both were
      teardrop shaped; an oblong mass of neurons at the caudal end with a long and thin
      trailing edge. The trailing edge of Gr?, however, curved dorsad towards the
      dorsal midline raphe of the caudal mesencephalon, while the trailing edge of Me5
      curved rostrad, parallel to the sulcus limitans of the sylvian aquaduct. The
      neurons of Gr? are mainly round, but in the caudal part of the nucleus some
      horizontally oriented fusiform neurons were observed. All neurons of Gr? were
      tiny. These results confirm that the generation sequence of the source nuclei is
      not a prime determinant of descent sequence along the spinal cord. The distance
      between the source nucleus and the entrance to the target seems of influence only
      in the most extreme cases (diencephalic source nuclei and the cerebral cortex).
      Descent velocity of the fiber fronts is not equal between different sources, nor
      is the descent velocity of specific fiber fronts constant over time. (ABSTRACT
      TRUNCATED)

PMID- 9257460
TI  - The role of microenvironment in axonal regeneration. Influences of lesion-induced
      changes and glial implants on the regeneration of the postcommissural fornix.

PMID- 9257461
TI  - Cigarette barons' bedfellows: ignorant, corruptible or both?

PMID- 9257462
TI  - Should Sri Lanka reconsider its rubella immunisation strategy?

PMID- 9257463
TI  - Pyrexia of unknown origin (PUO).

PMID- 9257464
TI  - Power cuts and EPI vaccine storage.
AB  - OBJECTIVE: To study the integrity of EPI vaccine storage during interruptions to
      the power supply. SETTING: Health centres in Colombo District. METHOD: An
      interviewer-administered questionnaire was used to collect information on staff
      compliance with regulations of the expanded program of immunisation (EPI) and
      alternative facilities available for refrigeration during power failure. The
      refrigerator and storage conditions were inspected. The stored vaccines were
      tagged with thermosensitive cold chain monitors, which were read on revisiting
      the clinic 14 days later. During the study period, power cuts of 2 hours'
      duration were in force daily. A control study was carried out when there was no
      interruption to power supply. RESULTS: Diphtheria-pertussis-tetanus (DPT) and
      measles vaccines had been exposed to temperatures outside the prescribed range
      during power cuts. Oral polio vaccine had adequate storage with power cuts of 2
      hours' duration. CONCLUSION: Alternative facilities for vaccine storage during
      power cuts were not available and the potency of DPT and measles vaccines were
      compromised with interruptions to power of 2 hours' duration or more.

PMID- 9257465
TI  - Pharmacologically induced penile erections in the assessment and treatment of
      erectile impotence: a preliminary study of 100 patients.
AB  - OBJECTIVE: To assess and compare the immediate and subsequent response to
      pharmacologically induced penile erections, using intracavernosal injections of
      papaverine. DESIGN: Preliminary, prospective study. SETTING: Male sexual
      dysfunction clinic at the National Hospital of Sri Lanka. PATIENTS: 100
      consecutive patients receiving 20 mg papaverine hydrochloride intracavernosally
      as the first dose. MAIN OUTCOME MEASURES: Assessment of the quality of the
      erection following the initial injection and determination of the optimum dose to
      achieve a normal erection; number who elected self-injection at home. RESULTS:
      Mean age of the 100 impotent men was 36.6 years and the mean duration of erectile
      dysfunction 43.9 months. Of men in the third decade 87.5% had a normal erection
      but only one-third of patients over 50 years showed a normal response. 16
      patients had a reasonably well established organic problem. 42% of patients had
      normal nocturnal or early morning erections. The drop-out rate after the initial
      injection was 17%, 19% of men had a normal erection with 20 mg papaverine and 67%
      had a normal response to 20 to 80 mg papaverine. Seven patients continued on the
      self-injection program. Prolonged erections were experienced by 6% of men (1.9%
      of injections). CONCLUSIONS: Intracavernosal injection of papaverine
      hydrochloride is effective in a dose of 20 to 80 mg.

PMID- 9257466
TI  - Middle ear surgery under local anaesthesia and sedation.
AB  - BACKGROUND: Middle ear surgical procedures such as myringoplasty, stapedectomy
      and tympanolasty are traditionally performed under general anaesthesia, with
      induced hypotension. METHODS: We performed middle ear surgery in 73 patients,
      without induced hypotension, under local anaesthesia with sedation, and assessed
      feasibility, safety and acceptability. RESULTS: The operating conditions achieved
      were good and the complications were minor. None required conversion to general
      anaesthesia. CONCLUSION: Middle ear surgery under local anaesthesia and sedation
      is safe and feasible. Prospective trials are needed to fully assess the
      advantages of this technique over general anaesthesia.

PMID- 9257467
TI  - Macrovascular disease in Sri Lankan kidney transplant recipients.
AB  - INTRODUCTION: Macrovascular diseases such as angina, myocardial infarction,
      stroke and peripheral occlusive arterial disease are common causes of mortality
      and morbidity in transplant patients. OBJECTIVES: To study the frequency and
      determinants if vascular disease in Sri Lankan patients with renal transplants.
      PATIENTS: A cohort of 237 renal transplant recipients (163 males (76%), mean age
      35.09, SD 11.05 years). SETTING: Patients under follow up at the Faculty of
      Medicine Transplant program. METHOD: Prospective study of a cohort of patients.
      RESULTS: Macrovascular diseases developed in 42% of transplant recipients. 5.6%
      had transient ischaemic attacks, 2.8% strokes, 18.2% angina, 8.4% myocardial
      infarctions, 2.3% underwent lower extremity amputations because of vascular
      insufficiency, 7% peripheral vascular occlusive disease and 49.5% were
      hypertensive. Male sex (odds ratio of 2.87, 95% CI 1.33-6.85, p = 0.006), serum
      cholesterol greater than 6.2 mmol/l at transplant (odds ratio 8.60, 95% CI 2.53
      38.9, p = 0.0001) at 5 years after transplant (odds ratio 10.25, 95% CI 1.22
      22.9, p = 0.01) were associated with a higher risk of macrovascular disease. Pre
      transplant diabetes was associated with a higher risk of macrovascular disease
      and lower extremity amputation (odds ratio 4.53, 95% CI 1.32-6.76, p = 0.007).
      CONCLUSIONS: Strategies to screen for and treat potential risk factors should
      form an integral part of the follow up for Sri Lankan and Asian kidney transplant
      recipients.

PMID- 9257468
TI  - Propanil poisoning.
AB  - OBJECTIVE: To document clinical features of propanil poisoning and discuss
      treatment. DESIGN, SETTING AND PATIENTS: Five patients treated in the University
      medical unit at the Karapitiya teaching hospital over the past two years.
      INTERVENTIONS AND MEASUREMENTS: Relevant laboratory investigations were done. The
      patients were treated on accepted lines. RESULTS: All had methaemoglobinaemia.
      The first patient died after severe poisoning in spite of intensive treatment.
      The second had severe poisoning requiring exchange transfusion and treatment with
      methylene blue. The third, fourth and fifth patients had mild poisoning which
      responded readily to oral methylene blue. The last patient had taken a
      combination of propanil and oxydiazone. The first and second patients had
      features of haemolysis and the second patient had acute hepatitis. CONCLUSIONS:
      Propanil poisoning is uncommon. Lower levels of methaemoglobin than were
      previously thought may be associated with a fetal outcome. Methylene blue is used
      in the treatment as it reduces blood methaemoglobin but in severe poisoning
      exchange transfusion may be necessary as a life saving measure.

PMID- 9257469
TI  - Donor valves as substitutes for heart valve replacement.
AB  - The main problems of heart valve replacement in Sri Lanka are the cost of
      prosthetic valves and anticoagulant related complications. The use of human donor
      heart valves (homografts; allogeneic heart valves [AHV]) will alleviate these
      shortcomings. Recipients of AHV do not require anticoagulant therapy. Moreover,
      cryopreservation of AHV offers the opportunity for the storage of valves for an
      extended length of time with the preservation of valve integrity which is
      essential for their function after implantation. A donor valve bank can
      potentially provide diameter matched valves for recipients. Current research
      suggests that the adverse immunological reactions initiated by AHV cause tissue
      degeneration in a proportion of these implants. However, the grafts may be
      improved before implantation during the disinfection and storage of the valves.
      In this essay an overview on the advantages of using AHV, current concepts of
      valve banking, recent advances in the understanding of AHV immunogenicity,
      emerging techniques for immunomodulation of AHV and the possibility of setting up
      a donor heart valve bank in Sri Lanka are discussed.

PMID- 9257470
TI  - Health of our elders.

PMID- 9257471
TI  - Practical aspects of aerosol therapy in asthma (3): Dry powder inhalers (DPI).

PMID- 9257472
TI  - Experiences of a forensic pathologist in the examination of a mass grave in
      former Yugoslavia.

PMID- 9257473
TI  - Ethical aspects of CMJ articles.

PMID- 9257474
TI  - Apocrine carcinoma of the breast masquerading as a tension cyst.

PMID- 9257475
TI  - First reported case of rabies in a horse in Sri Lanka.

PMID- 9257476
TI  - Holt-Oram (heart-hand) syndrome.

PMID- 9257477
TI  - Holoprosencephaly and cerebellar hypoplasia in a neonate with multiple congenital
      malformations.

PMID- 9257478
TI  - Nai habarala (Alocasia cucullata) fruits; analysed for potential hydrogen
      cyanide.

PMID- 9257480
TI  - Recurrent Guillain-Barre syndrome.

PMID- 9257479
TI  - Ivemark syndrome: a case report.

PMID- 9257481
TI  - Estimates of reports of notifiable diseases by general practitioners in regional
      Western Australia.
AB  - We surveyed the attitudes of general practitioners to the notification of
      gazetted diseases in the south-west of Western Australia. Notification rates were
      calculated from the number of notifications recorded by the Southern Public
      Health Unit or the Communicable Disease Control Program of the State Health
      Department, and the estimated population of the region, the metropolitan area and
      the State. Of the 80% of general practitioners responding to the survey, 96%
      advised they intended to notify all gazetted diseases they diagnosed.
      Notification rates in the south-west of Western Australia ranged from 380 to 900
      per 100,000 population, compared with approximately 450 per 100,000 population in
      the metropolitan area.

PMID- 9257482
TI  - Communicable diseases surveillance.

PMID- 9257484
TI  - The structural basis of maternal-fetal immune interactions in the human placenta.

PMID- 9257483
TI  - Immunogenetics of reproduction: an overview.

PMID- 9257485
TI  - Immunobiology of the decidua.

PMID- 9257486
TI  - Ontogeny of human natural and acquired immunity.

PMID- 9257487
TI  - Transfer of maternal leukocytes to the infant by human milk.

PMID- 9257488
TI  - Maternal T cell reactivity in pregnancy?

PMID- 9257489
TI  - Immunobiology of the trophoblast: mechanisms by which placental tissues evade
      maternal recognition and rejection.

PMID- 9257490
TI  - Traffic of leukocytes through the maternofetal placental interface and its
      possible consequences.

PMID- 9257491
TI  - Suppressive cellular and molecular activities in maternofetal immune
      interactions; suppressor cell activity, prostaglandins, and alpha-fetoproteins.

PMID- 9257492
TI  - The immunopathology of recurrent abortion.

PMID- 9257493
TI  - Popliteal artery entrapment syndrome: diagnosis and management.
AB  - A variety of anatomical abnormalities may product an external compression of the
      popliteal artery, resulting in a thrombotic occlusion. Between 1983 and 1995, 9
      patients presented a popliteal artery entrapment syndrome, bilateral in two
      cases. Ultrasonography, Angio-CT scan and MRI showed the abnormal structures and
      position of the popliteal artery on popliteal fossa. Arteriography detected an
      arterial compression in 6 limbs and occlusion in 4 limbs as well as an associated
      popliteal aneurysm in one patient and distal embolism in four. The abnormal
      medial head of the gastrocnemius muscle was resected in 8 limbs, while fibrous
      membranes were resected in 3 limbs. Autogenous vein replacement was performed in
      4 cases of popliteal artery occlusion and following resection of a popliteal
      artery aneurysm in one case. All patients recovered. In the followup period, the
      occlusion of the arterial reconstruction occurred after 28 months in one patient,
      with a mild claudication. Noninvasive vascular imaging techniques may allow early
      diagnosis and management of PAES, avoiding popliteal arterial wall lesions and
      its occlusion, with a better outcome.

PMID- 9257494
TI  - Lymphoma of the appendix. A case report.
AB  - Lymphoma of the appendix is exceptionally rare and the management of this
      condition is still controversial. A multimodality approach (surgery, radiation
      therapy, chemotherapy) is the optimal treatment. The Authors report a case of
      lymphoma of the appendix treated by right hemicolectomy and postoperative
      multiagent chemotherapy.

PMID- 9257495
TI  - Laboratory waste: the hidden threat to health care.

PMID- 9257496
TI  - Nucleolar organizer regions in neoplastic and non-neoplastic epithelium of the
      cervix.
AB  - Argyrophilic nucleolar organizer regions (Ag NORs) were counted in biopsies from
      203 cases of various lesions of the cervix. The mean number of Ag NORs per
      nucleus was significantly higher in CIN (4.05 +/- 0.04) and malignancy (5.50 +/-
      0.65) as compared to squamous metaplasia (1.74 +/- 0.32) and chronic cervicitis
      (1.54 +/- 0.42). Adenocarcinomas had higher Ag NOR counts compared to other
      carcinomas. Estimation of Ag NORs can be helpful in distinguishing benign lesions
      from CIN and malignancy of the cervix.

PMID- 9257497
TI  - Serological evidence for active Epstein-Barr virus infection in multifocal
      choroiditis.
AB  - Six patients, consisting of 4 males and 2 females with mean average age fo 29.20
      years, with variable picture of multifocal choroiditis were serologically
      investigated for their association with Epstein-Barr Virus (EBV) infection. IgG
      and IgM antibodies to EBV-Virus Capsid Antigen (VCA) were assayed by
      immunoperoxidase method on EBV infected lymphoblast cells (P3HR-1 Burkitt's
      lymphoma cell line). In these patients definite serological evidence of EBV
      infection with high titres of IgG and IgM antibodies to EBV-VCA was demonstrated
      suggestive of active continuing or persisting EBV infection.

PMID- 9257499
TI  - A correlative study of histology and imprint cytology in the diagnosis of
      gastrointestinal tract malignancies.
AB  - Endoscopic mucosal biopsies from 323 patients (201 from upper gastrointestinal
      tract and 122 from lower gastrointestinal tract) were studied to correlate the
      diagnostic efficacy of histology and imprint cytology in the diagnosis of
      malignant lesions of gastrointestinal tract. Of these 71 were from normal
      controls, 113 from benign lesions and 131 from malignant lesions. Histology
      showed no false positive reports but it was false negative in 6 cases (3 in
      oesophagus, 1 in stomach and 2 from colon). Imprint was false positive in 3 cases
      (2 oesophagus, 1 colon) and false negative in 2 cases (both oesophagus). The
      overall diagnostic accuracy of histology and imprint cytology in oesophagus,
      stomach and lower gastrointestinal tract was 95%, 98%, 98% and 95%, 100%, 98%
      respectively. When combined, the diagnostic accuracy increased to 98%, 100% and
      100% in oesophagus, stomach and lower gastrointestinal tract respectively. The
      sensitivity, specificity, positive predictive value, negative predictive value
      and overall diagnostic accuracy for histology and cytology irrespective of the
      site was 96%, 100%, 100%, 94%, 97% and 98.5%, 97%, 98%, 98%, 98% respectively.
      Thus imprint cytology can act as an adjunct to bioptic histology to increase the
      diagnostic efficacy and save the time but definitely it cannot replace it as
      chances of false positives are high.

PMID- 9257498
TI  - Haemostatic function in coronary artery disease (CAD).
AB  - Tests to evaluate haemostatic function bleeding time (BT), prothrombin time (PT)
      partial thromboplastin time with kaolin (PTTK), thrombin time (TT), platelet
      count, platelet function tests (platelet adhesiveness and microthrombus index)
      and plasma fibrinogen levels were performed in 30 patients of coronary artery
      disease (14 myocardial infarction, 16 angina pectoris) and 20 age and sex matched
      controls. There was no statistically significant difference in platelet
      adhesiveness and mean microthrombus index in patients and controls. The BT, PT,
      PTTK and TT were normal in all patients and controls. Stepwise logistic
      regression analysis showed that plasma fibrinogen was an independent risk factor
      in the production of CAD.

PMID- 9257500
TI  - Leucocyte alkaline phosphatase activity in patients with squamous cell carcinoma.
AB  - Alkaline phosphatase have been demonstrated histochemically in the cytoplasm of
      neutrophils. Altered LAP activity has been observed in a number of conditions.
      Increased values are found in various inflammatory lesions where as in different
      malignancies LAP falls. Our study was aimed to see the alteration in LAP activity
      in case of squamous cell carcinoma. The study was carried out in peripheral blood
      smears of 185 cases (110 cases of squamous cell carcinoma and 75 of normal
      persons). After histochemical staining, LAP scoring was done. LAP score in
      Squamous cell carcinoma (mean +/- SD = 57.41 +/- 16.9). No significant difference
      in LAP score was found according to the site and grade of carcinoma, and in
      relation to metastasis. 43 cases were followed up after variable periods of
      treatment. LAP score was found to be significantly raised following treatment,
      (mean +/- SD = 21.14 +/- 5.94, p < 0.001). It is concluded that LAP scoring might
      be used as a cheap and simple technique to diagnose occult malignancies and to
      assess the response to therapy.

PMID- 9257501
TI  - Churg Strauss syndrome-clinicopathological aspects--report of a case.
AB  - An elderly person presented with exertional dyspnoea, cough, rhinorrhea and
      multiple swelling in submandibular region. This case was found to have marked
      eosinophilia with upper, as well lower respiratory tract involvements. Erroneous
      treatment patient received in past for pulmonary tuberculosis without any
      beneficial result. Open lung biopsy was undertaken, revealed evidence of
      vascultitis and perivascular inflammatory changes. The case findings and
      histopathological discussions are reviewed briefly.

PMID- 9257502
TI  - Solid cystic tumour of the pancreas-clinico-pathological study of three cases.
AB  - During a period of four years three cases of solid and cystic (papillary) tumour
      of the pancreas were encountered. The patients presented predominantly with chief
      complaints of lump abdomen associated with dull aching pain in right
      hypochondrium. Radiologically diagnosis was suspected in two cases. Excessive
      bleeding during surgery was observed in two cases. In two survivors no recurrence
      or distant metastasis was noted after surgical excision (follow up 6 months to
      3.5 years), third patient died after eight hours of operation.

PMID- 9257503
TI  - Persistent mullerian duct syndrome. A report of two cases.
AB  - Two cases of persistence of Mullerian duct structures in phenotypic male patients
      are reported. One of these was aged 16 years and the other 10 months. Both
      patients had cryptorchidism and inguinal hernia for which they were operated
      upon. In both patients parts of uterus and fallopian tubes were identified in the
      hernial sac. Endocrine evaluation was normal. Karyotyping was performed in the
      second case which revealed a normal male genotype of 46 XY.

PMID- 9257504
TI  - Fine needle aspiration cytology of papillary carcinoma thyroid with Hashimoto's
      thyroiditis--report of two cases.
AB  - Two cases of papillary carcinoma of thyroid with clinically unsuspected
      Hashimoto's thyroiditis were diagnosed on Fine Needle Aspiration Cytology (FNAC)
      in females aged 22 yrs, and 57 yrs., who presented with a solitary thyroid
      nodule. The frequency of carcinoma in Hashimoto's thyroiditis varies between 0.5
      to 23.7%, depending on the stringency of diagnostic criteria applied. We believe
      that this possibility must be kept in mind when ever an aspirate of a solitary
      nodule shows profuse lymphocytes and Hurthle cells.

PMID- 9257505
TI  - Osteoclastoma like giant cell tumour of the thyroid--a variant of
      undifferentiated carcinoma--a case report.
AB  - A case of osteoclastoma like giant cell tumour of thyroid is reported in a
      patient who presented with dysphagia and swelling in the neck. The light
      microscopy showed numerous osteoclast-like giant cells embedded in mononuclear
      stromal cells, the overall appearance resembling that of giant cell tumour of
      bone.

PMID- 9257506
TI  - Laboratory waste disposal.

PMID- 9257507
TI  - The many faces of sleep disturbance.

PMID- 9257508
TI  - The hysteresis loop as a model for low back motion analysis.
AB  - The human low back is highly susceptible to dysfunction. Many diagnostic and
      treatment modalities for low back problems are used subjectively in clinical
      practice. Availability of a quantitative reference of back motion could improve
      practice efficiency. This article describes hysteresis and the hysteresis loop as
      an objective measurement model of low back motion. The authors constructed an
      instrument that quantifies force displacement responses of the lower back in
      passive subjects. Hysteresis loops generated by this instrument lay a scientific
      foundation on which to base diagnostic procedures and therapeutic measures.

PMID- 9257509
TI  - Bicycle helmet laws: a current perspective.
AB  - Bicycle-related head trauma is a significant source of death, disability, and
      health-care costs in the United States. Bicycle helmets are effective safety
      devices that can reduce most of this burden on society. Bicycle helmet laws and
      education programs are effective ways to increase helmet use rates. Osteopathic
      physicians can play a prominent role in bicycle-related injury prevention by
      actively supporting and participating in helmet legislation, research, and
      community-based education. This article provides a current summary of state
      bicycle helmet laws and highlights research that supports the effectiveness and
      necessity of these laws. The recent trend in safety standards for bicycle helmets
      is included to give a comprehensive view of bicycle helmet law in the United
      States.

PMID- 9257510
TI  - An osteopathic prescription for medical education reform: Part 1. Curriculum and
      infrastructure.
AB  - Medical education has not kept pace with the evolving healthcare system.
      Criticism from industry and policy observers focuses on four major areas
      requiring reform: the curriculum, the fragmented educational infrastructure, the
      specialist-to-generalist mix, and the alienation from community and public
      health. The dominance of managed care organizations in the delivery and financing
      of healthcare is forcing a new set of physician competencies to the fore and
      changing projections of physician manpower and specialty needs. The authors
      address the four major criticisms from a uniquely osteopathic point-of-view. In
      this first of two articles, the authors describe the evolving osteopathic medical
      education model, and then employ a medical analogy to diagnose the causes of and
      propose treatments for curricular issues and infrastructure fragmentation. In the
      second article of the pair, they explore the causes of and propose strategies to
      address the generalist-to-specialist imbalance and the alienation of medicine
      from community and public health; the article also explores the role of
      technology in support of reform. In each article, the authors propose treatments
      to correct the problems in the osteopathic medical education model, and conclude
      that the profession is well-positioned to lead medical education reform.

PMID- 9257511
TI  - Superior vena cava syndrome caused by a benign retrosternal multinodular goiter.
AB  - Retrosternal thyroid accounts for a significant percentage of anterior
      mediastinal masses, but has been described very rarely as the cause of superior
      vena cava (SVC) syndrome. Most cases of SVC syndrome occur as a complication of
      malignancy. The authors report the case of a patient with few respiratory
      symptoms, mild upper airway obstruction, and SVC syndrome caused by a benign
      retrosternal multinodular goiter.

PMID- 9257512
TI  - Spontaneous expulsion of an intravesical bullet.
AB  - Gunshot wounds of the pelvis are not uncommon. Penetrating injuries of the
      bladder are usually documented by means of a cystogram. The patient reported here
      was shot with a small caliber bullet. No extravasation was demonstrated. The
      authors caution that not all penetrating injuries to the bladder will demonstrate
      extravasation on a properly performed cystogram.

PMID- 9257513
TI  - Comparison of performance on the American Osteopathic Board of Internal Medicine
      certifying examination 1986 to 1996 by type of residency.
AB  - The purpose of this study was to determine if internal medicine residency type or
      location was associated with differences in performance of candidates as measured
      by the internal medicine certifying examination. Included in the study were all
      first-time taker candidates for the 1986 to 1996 American Osteopathic Board of
      Internal Medicine certifying examinations in internal medicine. Group analysis
      was performed based on the type of residency track leading to board eligibility:
      (1) traditional internship plus 3 years of internal medicine residency; (2)
      traditional internship plus 2 years of internal medicine residency and 1 year of
      subspecialty training; (3) specialty track internship plus 2 years of internal
      medicine residency; and (4) traditional internship plus 3 years of allopathic
      internal medicine residency. Subgroup analysis of the subspecialty track group
      was performed to determine if any particular subspecialty-trained subgroup
      performed better than the others. Results indicate that all groups had similar
      scores and pass rates except for the allopathic-trained residents, whose scores
      and pass rates were lower. Subgroup analysis of the subspecialty-trained
      candidates revealed that procedure-oriented subspecialty candidates performed
      similar to non-procedure-oriented candidates. No gender differences were noted in
      scores or pass rates. It is concluded that the overall performance of candidates
      is equivalent for each of the residency training tracks developed by the American
      College of Osteopathic Internists. Future performance on the recertification
      examination will need to be tracked to determine if these trends continue for
      practicing internists.

PMID- 9257514
TI  - Suicides in Hong Kong, 1981-1994.
AB  - Suicide in Hong Kong is experiencing a slight upward trend. The standardized
      suicide rate increased by 9.8%, from 10.3 per 100,000 population in 1981 to 11.3
      per 100,000 in 1994. About 57% of the increase can be explained by a change in
      the age composition and the ageing problem in Hong Kong. Suicide ranked seventh
      in the ten leading causes of death since 1985. It was the leading cause of death
      in females aged 15-24 years. The female suicide rate in Hong Kong was among the
      highest in the world. The suicide rate increased steadily with age. Males aged 75
      years or over had the highest suicide rate among all age groups in the
      population. Furthermore, in single males aged 60 years, the suicide rate was 80
      per 100,000. The suicide rate for economically inactive persons was 4 times more
      than for the active. Jumping has become increasingly common and seems to
      substitute for other methods of suicide. The years of potential life lost were
      342 years per 100,000 population in 1994.

PMID- 9257515
TI  - Suicide among young rural Australians 1964-1993: a comparison with metropolitan
      trends.
AB  - The study tested hypotheses that from 1964 to 1993: (1) suicide rates among
      Australian 15- to 24-year-old males rose more sharply in rural than metropolitan
      areas; (2) firearm suicide rates among 15- to 24-year-old males, declining
      throughout Australia recently, rose continuously in rural areas; (3) suicide
      rates among 15- to 24-year-old females did not change significantly in either
      metropolitan or rural areas. Suicides of those aged 10-24 years recorded by the
      Australian Bureau of Statistics (ABS) were classified according to the subject's
      residential grouping. Rates were calculated using ABS population data
      corresponding to these groupings. Results were analysed using log-linear analysis
      and chi-square statistics. The results supported the first two hypotheses, but
      not the third. Suicide rates for 15- to 24-year-old males rose by a factor of 2.2
      in metropolitan areas, by 4-fold in towns with populations between 4,000 and
      25,000, and by 12-fold in towns with populations less than 4,000. Male firearm
      suicide rates continued to rise in rural areas, and the greatest proportion of
      deaths in those locations were by firearms, though male hanging rates increased
      most in recent years in all locations. Female youth suicide rates did not change
      overall, but in towns with populations less than 4,000, they increased 4.5-fold.
      Possible explanations for this epidemic, which are mostly speculative and require
      confirmation, are discussed.

PMID- 9257516
TI  - Psychiatric morbidity following a natural disaster: an Australian bushfire.
AB  - This study investigated the prevalence of mental health problems after a major
      bushfire in Australia and examined the validity of the General Health
      Questionnaire (GHQ) (Goldberg 1978) against the Anxiety, Affective and Post
      Traumatic Stress Disorder modules of the Diagnostic Interview Schedule (DIS;
      Robins et al. 1981). Study 1 was carried out 12 months after the Ash Wednesday
      bushfires and sought to include all the victims of the fires. Study 2 was
      conducted 20 months after the fires and included a sample of victims who had
      experienced major losses in the fires. Twelve months after the fires, 42% (n =
      1,526) of the victims were defined as a potential psychiatric case using the GHQ.
      This rate indicated a significantly greater level of morbidity than found in
      communities that have not experienced a natural disaster. Twenty months after the
      fires, 23% (n = 43) were defined as "cases". The 28-item GHQ was found to be a
      valid instrument for defining the presence of psychiatric disorder in a disaster
      effected community. The findings demonstrated that lasting psychiatric morbidity
      is associated with natural disasters.

PMID- 9257517
TI  - Defensive styles and psychological symptoms among Chinese adolescents in Hong
      Kong.
AB  - Specific defenses were assessed in a cohort of 490 Chinese adolescent boys and
      girls in Hong Kong using the Chinese version of the short form of the Defense
      Style Questionnaire (DSQ). Commonly employed defenses included anticipation,
      sublimation, and reaction formation, indicating that adolescents tended to deal
      with stressors and emotional conflicts with relatively mature or adaptive
      defenses. Factor analysis revealed that a mature or adaptive defensive style
      could generally be distinguished from an immature or maladaptive defensive style,
      but a neurotic defensive style was not differentiable for this group of
      adolescents. Results also indicated that general and specific psychological
      symptoms were associated with the use of immature defenses characterized by
      somatization and externalizing emotional conflicts through acting out and
      misattribution. The use of the DSQ for assessing defenses among Chinese
      adolescents and cross-cultural comparisons are discussed.

PMID- 9257518
TI  - Life stress, social support and psychological distress in late adolescence.
AB  - Psychological distress in high-school students was examined in relation to
      negative life events, long-lasting adversities and perceived social support from
      the family, friends and the school class. Academic problems increased the symptom
      levels of psychological distress, and social support from family and social
      support from friends reduced the symptoms among males and females. For females,
      social support from school class-mates and problems with parents and friends also
      had direct independent effects on symptom levels. An effect of the total number
      of long-lasting adversities was significantly stronger for females than males.
      The buffer hypothesis was supported: both an increase in social support from
      parents and social support from peers reduced the effect of negative life events.

PMID- 9257519
TI  - Religious involvement and depression in older Dutch citizens.
AB  - It has been suggested that religiosity helps prevent depression in older people.
      This study examines the association between religious involvement and depression
      in older Dutch citizens and focuses on models of the mechanism in which religious
      involvement has an impact on other factors related to depression. The subjects
      were 2,817 older adults aged 55-85 years living in the community who participated
      in the Longitudinal Aging Study Amsterdam. Depressive symptoms were assessed
      using the Center for Epidemiologic Studies Depression Scale (CES-D). Religious
      involvement was assessed using items on frequency of church attendance and
      strength of church affiliation. Further data were collected on physical health,
      size of social network, social support, sense of mastery and self-esteem. As in
      North American studies, religious involvement appeared to be inversely associated
      with depression, both on symptom and syndrome levels. Controlling for
      sociodemographics, physical impairment and network support did not substantially
      affect this association, particularly among subjects aged 75-85 years. The
      inverse association between religious involvement and depression was not
      selectively more pronounced among older people with physical impairments.
      However, the association appeared to be most specific for subjects with a small
      social network and those with a low sense of mastery.

PMID- 9257520
TI  - The quality of life of patients with paranoid schizophrenia in London and Berlin.
AB  - This study compared the subjective and objective quality of life and needs of
      patients with paranoid schizophrenia between inner city areas in Berlin (69
      patients) and London (75 patients). Quality of life was assessed by means of the
      Lancashire Quality of Life Profile (German version Berliner
      Lebensqualitatsprofi), and need was quantified using the Camberwell Assessment of
      Need (German version Berliner Bedurfnisinventar). The hypotheses tested were that
      although Berlin patients may rate more highly on objective quality of life
      measures, the subjective quality of life would be similar as patients would judge
      their quality of life against their local expectations. The findings supported
      the first part of the hypothesis as on the objective measures the Berlin group
      was significantly better off financially and in living conditions, and had
      significantly fewer material needs. However, despite having more severe
      psychopathology, the Berlin groups' scores on global subjective quality of life
      were also higher. On particular life domains, subjective quality of life did not
      always reflect objective measures and sometimes went in the reverse direction. We
      concluded that the relationship between subjective and objective quality of life
      is complex, and great caution must be exercised in making quality of life
      comparisons between different cultures.

PMID- 9257521
TI  - Epidemiology of psychiatric care of patients with severe mental disorders in
      Italy. Rationale and design of a prospective study, and characteristics of the
      cohort. Italian Collaborative Study Group.
AB  - The rationale and design of a large, multicentre, prospective follow-up study on
      the outcome of severe mental disorders is presented. The study is currently under
      way in Italy, where psychiatric care has been uniquely characterised since 1978
      by the statutory prohibition of admitting patients to psychiatric hospitals. The
      main purpose of the study is to describe the 5-year outcome of patients with a
      diagnosis of schizophrenia, paranoid disorder, affective psychosis, reactive
      psychosis or personality disorder with respect to five areas (clinical condition,
      personal autonomy, work, and family and social relationships); a secondary
      objective is to describe the heterogeneity of practices and resources of
      psychiatric services. The study is being carried out by 76 outpatient psychiatric
      services throughout the country, covering approximately one-tenth of the Italian
      population.

PMID- 9257523
TI  - Cell death in vertebrates: lessons from the worm.

PMID- 9257522
TI  - A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a
      Finnish national birth cohort. Clinical and research diagnoses of schizophrenia.
AB  - As a prerequisite to the use of the Finnish National Hospital Discharge Register
      in psychiatric epidemiological research, we studied the diagnostic reliability of
      the register in terms of the psychiatric morbidity experienced by a national
      birth cohort. We investigated all entries to the register for a sample based upon
      the Northern Finland 1966 birth cohort at the age of 16 years (n = 11017). Until
      the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis
      indicating a psychiatric illness, 37 of them being schizophrenia. When
      operational criteria (DSM-III-R) were applied to clinical information in the
      available original hospital records for cases of psychosis, personality disorder
      and substance abuse (n = 249), 71 fulfilled criteria for schizophrenia, including
      all of the 37 cases in the register and an additional 34 (48% false-negatives),
      most frequently diagnosed in the register as schizophreniform or other psychosis.
      Despite the official use of DSM-III-R nomenclature, it appears that the clinical
      concept of schizophrenia in Finland, manifest within the register, remains very
      restrictive. The application of operational criteria is a necessary prerequisite
      for scientific research on schizophrenia.

PMID- 9257524
TI  - Whole genome radiation hybrid mapping.

PMID- 9257525
TI  - MAD-related proteins in TGF-beta signalling.

PMID- 9257526
TI  - Evolution and orthology of hedgehog genes.

PMID- 9257527
TI  - Quantification of minute levels of beta galactosidase in individual 2- to 16-cell
      stage mouse embryos.

PMID- 9257528
TI  - An easy non-radioactive procedure to check the quality of the ligation steps
      during the construction of cDNA libraries.

PMID- 9257530
TI  - A technique for the direct cloning of RT-PCR fingerprinting products.

PMID- 9257529
TI  - Differential mRNA display using anchored oligo-dT and long sequence-specific
      primers as arbitrary primers.

PMID- 9257531
TI  - A rapid method for FISH analysis on interphase nuclei extracted from cryofixed
      tissues.

PMID- 9257532
TI  - An improved protocol for purification of 35S-labelled oligonucleotide DNA probes
      for in situ hybridization applications.

PMID- 9257533
TI  - Anti-gene therapy: the use of ribozymes to inhibit gene function.
AB  - The ability of certain enzymatic RNA molecules, or ribozymes, to site
      specifically cleave other RNA molecules opens new vistas in gene therapy.
      Ribozymes can be designed to target specifically a particular mRNA and inhibit
      protein expression, permitting 'anti-gene' therapy. Here, we describe the
      progress towards developing ribozymes for use in gene therapy applications.
      Significant advances have been made in understanding ribozyme transcription unit
      design and the first clinical tests of ribozyme safety in humans are soon to be
      initiated.

PMID- 9257534
TI  - Exploring the gene with X-rays.
AB  - X-rays were discovered 100 years ago. Their effects on living cells and on
      mutation were quickly recognized. This article discusses a classic paper that
      sought to use X-rays to estimate the size of the gene and question mechanics to
      explain its impressive stability.

PMID- 9257535
TI  - Base composition and gene distribution: critical patterns in mammalian genome
      organization.
AB  - Recent success in developing transcriptional maps of large genomic regions
      provide excellent opportunities for the investigation of mammalian genome
      organization. Detailed definition of organizational features will, in the short
      term, aid in prioritizing genomic sequencing efforts and in interpreting
      sequencing results and, in the long term, will surely provide insights into the
      structural, functional and evolutionary basis for the mammalian chromosome and
      chromosomal banding patterns. For such efforts, human chromosome 21 provides an
      excellent model system because the physical and clone maps are detailed, and
      several transcriptional mapping projects have provided large numbers of novel
      genes. It is, therefore, valuable at this point to examine these transcriptional
      mapping data and to compare them with the isochore model of the mammalian genome,
      which describes patterns in base composition and predicts gene distributions. Not
      only do compelling organizational patterns appear, but new questions about
      additional possible patterns in gene size, structure, conservation and
      transcription can be asked.

PMID- 9257536
TI  - The vertebrate organizer: structure and molecules.
AB  - Since the identification of the first organizer gene, goosecoid, more than 15
      organizer-specific genes have been characterized. Here, we present our current
      understanding of the roles of these molecules in amphibians fish and amniotes and
      show how there identification has confirmed Spemann's original proposition that
      the vertebrate organizer is subdivided into separate domains: the head, trunk and
      tail organizers.

PMID- 9257537
TI  - Resources for human geneticists.

PMID- 9257538
TI  - Fluid and electrolyte therapy in West African adults.

PMID- 9257539
TI  - Differentiation of dual seropositivity to HIV 1 and HIV 2 in Ghanaian sera using
      line immunoassay (INNOLIA).
AB  - Two hundred serum samples from AIDS-like patients, blood donors and miscellaneous
      patients were screened by ELISA for HIV 1-2. Repeatedly positive samples were
      confirmed using the Western Blot (WB). Twenty samples that were dual positive
      were further analysed by Innolia, which contains synthetic or recombinant
      antigens in HIV-1 and HIV-2. Only 5 of the samples were dual positive. The need
      for further analysis of dual WB results is re-emphasized.

PMID- 9257540
TI  - Impact of guineaworm disease on agricultural productivity in Owo local government
      area, Ondo state.
AB  - Of the 500 Cocoa farmers infected with guineaworm in Amurin, 74.3% of the farmers
      were incapacitated for 3 months without going to their farms while 25.7% mostly
      those who sought the orthodox form of treatment were incapacitated for about 4
      weeks. This resulted in the loss of 9,566 bags of the potential harvest of the
      farmers which translates to N2,442,000.00 for the period. The sustantial part of
      this loss was from cocoa (N1, 570,000.00), a major export crop in Nigeria. The
      losses experienced were as a result of inability to plant and supervise the farm.
      An average of 45,000 mandays were lost due to guineaworm infection at a value of
      N54.27 k per individual for incapacitation for a day and a farmer infected with
      guineaworm loses 19 bags of his potential harvest within the infection duration,
      which translates to N4,884.00. Guineaworm disease is a major preventable cause of
      agricultural work loss and significant impediment to agriculture, the dominant
      occupation in Nigeria, which implies that guineaworm disease poses large threat
      to food availability.

PMID- 9257541
TI  - Paediatric neurologic emergencies at the University of Nigeria Teaching Hospital,
      Enugu.
AB  - Four hundred and sixty-seven children, aged from birth to 16 years (mean age:35.9
      months), presented with emergency neurological problems to the Children's
      Emergency Unit (CHER) of the University of Nigeria Teaching Hospital, Enugu over
      a 12-month period. This accounted for 11.1% of all the cases seen in the Unit
      during that period. There was a male:female ratio of 1.55:1. A significantly
      higher number of cases presented during the rainy season (May to October) than
      during the other months of the year. Febrile convulsion was the most common
      problem, with 132 cases (28.3%), followed by meningitis (18.2%) and afebrile
      seizures (15.8%). One hundred and ninety-two patients (37.7%) were discharged
      home, while 36 (7.7%) died. The findings from the study are discussed and
      compared with data from other centres. Recommendations that may help to reduce
      mortality from neurologic emergencies in children, are made.

PMID- 9257542
TI  - The cost effective medical treatment of suppurative otitis media in a Nigerian
      environment.
AB  - The microbes isolated from the cultures taken from the discharging ears of 63
      patients with Otitis media treated in a hospital in Warri in 1991 were analysed.
      Pseudomonas, streptococcus, Staphylococcus and Proteus were the major organisms
      isolated in order of their prevalence. All show highest sensitivity to
      Gentamycin. The author found 24 aural preparations in the MIMS of 1992 and
      checked the availability and cost of these in the Nigeria environment and came
      out with the possible cost effective suggestions for the treatment of acute
      otitis media in this environment based on these micro-organisms.

PMID- 9257543
TI  - Psychiatric disorders among offender patients in the Accra Psychiatric Hospital.
AB  - Details of personal data, criminal activity and the clinical diagnosis at the
      time of offence of one hundred and thirty (130) mentally ill offenders confirmed
      in the Accra Psychiatric Hospital were collected and analysed, to determine the
      common psychiatric disorders implicated in crime, and the vulnerable age group of
      such offender patients. Further, their current mental state was examined. The
      crime rate was found to be highest among late adolescents and young adults. The
      commonest psychiatric disorders implicated in various criminal acts were the
      psychotic states especially schizophrenia and drug induced psychotic state.
      Moreover there was a small group of offenders diagnosed as suffering from harmful
      drug use without associated psychoses. The duration of these mentally ill
      offenders was found to be very long although the majority showed no evidence of
      florid psychotic symptoms. The implications of the findings were discussed and
      suggestions made regarding the disposal of mentally ill offenders for future
      consideration.

PMID- 9257544
TI  - The immunization status and level of knowledge about hepatitis B virus infection
      among Nigerian surgeons.
AB  - Hepatitis B virus (HBV) infection is an occupational risk of surgeons especially
      in developing countries where asymptomatic carrier rate is about 15%. Despite
      better knowledge about mode of transmission and methods of prevention including
      use of active immunization, it still remains a threat. In this study, a
      questionnaire survey of Nigerian surgeons was conducted to ascertain their
      knowledge, and immunization status against HBV infection. Our study showed a 9.3%
      incidence of clinical HBV infection, poor perception of risk of infection, poor
      local availability of vaccines, and low uptake where same was available. Reasons
      cited for non-immunization are lack of awareness, cost, inertia and non
      availability of vaccines. Only 10.2% of our respondents always used barrier
      methods, and 77.7% of our respondents do not check the immune status of their
      patients after sustaining an intraoperative sharp injury. The overall level of
      knowledge about HBV infection was deemed poor. We conclude with recommendations
      on how to improve knowledge about HBV infection and uptake of vaccines.

PMID- 9257545
TI  - Blood demand in a teaching Hospital in Ghana.
AB  - The blood requirement per acute hospital bed and the pattern of the supply were
      determined using the number of units of blood supplied to the various wards of
      the Korle Bu Teaching Hospital between 1987 to 1993. The mean yearly supply and
      mean monthly supply and their standard deviations were determined. The former was
      used to calculate the blood needs per bed in the clinical departments and also
      per adult and paediatric bed respectively. The rainfall figures in mm per month
      and year were used to determine the mean rainfall for the various months and
      years under study. This was superimposed over the blood requirement. There were
      1143 adult acute beds with blood requirement of 5.16 units per bed compared with
      231 paediatric beds needing 9.2 units per bed. The mean blood requirement per
      acute hospital bed which is found to be applicable also to regional hospitals is
      5.5. Paediatric blood usage was extremely high in July to September after the
      April to July rains and also very high in the years with the highest rainfall.

PMID- 9257546
TI  - HIV-1 and HIV-2 in Ghana, west Africa: community surveys compared to surveys of
      pregnant women.
AB  - We conducted a population-based serosurvey of HIV-1/2 in 2,410 residents of two
      urban and two rural areas of southern Ghana, West Africa and compared the results
      to serosurveys of 1,417 pregnant women. Using conservative criteria, we found the
      prevalence of HIV-1/2 in community survey adults (> 15 years old) to be 1.5% in
      women and 1.0% in men. Among pregnant women, the prevalence was 9.3% in one rural
      area but only 1.0% in other areas. Many samples, especially among the pregnant
      women were HIV-1 and -2 dual reactive on serology. We attribute the disparity
      between prevalence in the community survey participants and pregnant women to
      local socio-economic factors. Women in this area have a tradition of working
      throughout West Africa as trader/ commercial sex workers. When pregnant or ill,
      they return to their home villages to be with their families. HIV surveillance
      programs which rely on pregnant women need to be sure that sampled populations
      are truly typical of the communities they are intended to represent.

PMID- 9257547
TI  - Isolation of Nigerian strains of measles virus.
AB  - We have recently succeeded in isolating two measles viruses, Ibn H13153 and Ibn
      H13154 from the peripheral lymphocytes of two unvaccinated 9 and 12 month old
      outpatient children at the Institute of Child Health, University College Hospital
      Ibadan, Nigeria. The viruses have undergone six serial passages in B95a and Vero
      cell lines where characteristic measles cytopathic effects (CPE) have been
      noticed. The viruses have been confirmed to be measles by Haemagglutination
      Inhibition (HI) test and the Indirect Immunofluorescent antibody Test (IFT). Both
      isolates agglutinated 0.75% monkey rbc. The HA titres were 1:40 and 1:80
      respectively. Antigens from the known positive Edmonston strain and uninoculated
      Vero cell line gave an HA titre of 1:160 and 1:0 respectively. Further
      characterisation with respect to the polypeptide and DNA components is under way.

PMID- 9257548
TI  - Spirometric measurements in healthy Sierra Leoneans.
AB  - Pulmonary Function Tests(PFTS) are useful in the diagnosis and management of
      respiratory disorders. They provide an objective and quantitative measure of some
      aspects of brocho-pulmonary function. For meaningful interpretation of PFTs, an
      individual's own previous baseline results compared with current results are
      preferred, but in the absence of such baseline values, standard normograms may be
      used. Since lung function values are influenced by genetic, environmental,
      nutritional, and several other factors, it is important for every laboratory to
      use normograms that reflect these important factors. The results presented here
      are the first baseline data on pulmonary function (VC, FVC, FEV1, and FEV%) in a
      wide cross-section of healthy Sierra Leoneans.

PMID- 9257549
TI  - Spontaneous gun pellet migration in the brain.
AB  - Majority of airgun injuries in the Kingdom of Saudi Arabia are accidental and
      involve children and adolescents. Potentially lethal penetrating injuries to the
      head often result from airguns. Computed tomography (CT) is the imaging modality
      of choice to determine the location of the pellet, and any associated brain
      parenchymal damage or haematoma formation. CT is also useful in demonstrating the
      fracture at the entry site of the pellet and any bone fragment which may be
      propelled into the brain. Although there have been a few case reports of
      spontaneous migration of metallic foreign body within the brain in the world
      literature, this case highlight the speed with which it can occur, even in a
      patient on complete bed rest.

PMID- 9257550
TI  - Acid ingestion in a 2-day old baby.
AB  - The incidence of chemical burns is low when compared to thermal burns. It can
      occur in little children accidentally if chemicals are left within their reach. A
      case is presented of a 2-day old male child who ingested a corrosive substance in
      unknown circumstances. He developed severe respiratory problems necessitating
      endotracheal intubation, and later died from acute necrotizing oesophago
      gastritis and lung collapse. The severity of damage caused by corrosive chemicals
      is discussed and the role of the anaesthetist in the initial management is
      highlighted.

PMID- 9257551
TI  - Issues related to school attendance of black baccalaureate nursing students.
AB  - Schools of nursing are facing the challenge of educating diverse groups of
      students. This research examined the differences between Black and non-Black
      baccalaureate nursing students in the level of importance of concerns and issues
      related to academic, financial, psycho-social, and personal areas of student
      life. In this study, two data collection methods were used, questionnaire and
      interview. The greatest differences were seen in the areas of financial and
      psycho-social. Strategies to assist students need to start as soon as possible
      and continue post graduation.

PMID- 9257553
TI  - Chairman's message. Fact or fantasy?

PMID- 9257552
TI  - Navigating a nursing curriculum: bridges and barriers.
AB  - As increasing numbers of students from non-traditional sources enter the
      baccalaureate nursing program, retention of these educationally, socially, and
      economically disadvantaged and older students have become important to a nursing
      program's continued viability. To retain these students, nurse educators need to
      become more sensitive to the educational needs of these students. Through focus
      groups used to survey sophomore, junior, and senior nursing students, researchers
      identified academic and non-academic resources cited by successful traditional
      and non-traditional students. A telephone survey of local nursing programs, by a
      third researcher, identified student resources at other statewide baccalaureate
      nursing programs. Participating students cited curriculum resources most often,
      with emotional support and academic resources of next importance. Students also
      expressed frustration regarding accessing resources (e.g., class time, office
      support, parking). The long term goal was to develop a resource program for non
      traditional nursing students.

PMID- 9257554
TI  - The case for the third person...

PMID- 9257556
TI  - 18th and 19th century surgery.

PMID- 9257555
TI  - Surgical implantation for bone anchored hearing aid.

PMID- 9257557
TI  - A special trip.

PMID- 9257558
TI  - Troubled waters: irrigation equipment re-used during cystoscopic procedures.

PMID- 9257559
TI  - Xenotransplantation and the law.

PMID- 9257560
TI  - PC heaven--Part 3. Don't forget the software!

PMID- 9257562
TI  - Medical-technical safety in an operating department.

PMID- 9257563
TI  - Reuse of single use items in minimal access surgery.
AB  - UK Government guidelines state that single use instruments, including those used
      in minimal access surgery, should not be reprocessed because of the risk of
      patient injury. In order to determine the incidence of this practice in minimal
      access surgery a questionnaire was issued to all participants of an Advanced
      Laparoscopy for Theatre Personnel course between 1994 and 1996. There was a 55%
      response rate. 27% of respondents had resterilised an instrument within the past
      year. More senior nurses resterilised more often and the request was usually made
      by Senior Registrars and Consultants, 52% of resterilised instruments were used
      with diathermy, the commonest being scissors. The practice was almost exclusive
      to the NHS. Since the course 44% of respondents have changed their practice.
      These results have implications for patient safety, staff indemnity, education
      and training for nurses and surgeons involved in minimal access surgery.

PMID- 9257564
TI  - Practical cell saving.

PMID- 9257565
TI  - The role of the cardiac perfusionist.

PMID- 9257566
TI  - Life after 'G' grade?

PMID- 9257567
TI  - Hospital drama.

PMID- 9257568
TI  - PC heaven--Part 4. Life as we know it.

PMID- 9257569
TI  - Music therapy.

PMID- 9257570
TI  - Alcohol attributable fractions for trauma in South Africa.
AB  - The misuse and abuse of alcohol is widespread in South African society and is
      likely to have a large impact on the economy. A major burden is borne by the
      hospital care system, in particular the cost of alcohol-related trauma. The
      purpose of this study was to estimate the cost of alcohol misuse in terms of
      fatal and non-fatal trauma. The design of the study was a cross-sectional survey
      of key informants. Each key informant was mailed a list of 11 trauma categories
      found to be linked to alcohol in both the local and international literature.
      They were asked to make an estimate of the alcohol attributable fraction (AAF)
      for each trauma category, based on their clinical experience and knowledge of
      empirical research. The median estimates for each trauma category showed that
      alcohol misuse could be linked to a substantial amount of mortality and
      morbidity, particularly with respect to motor vehicle trauma and interpersonal
      violence. These AAF estimates were supported by the findings of other empirical
      research conducted in South Africa, as well as by the literature on mortality
      data in the U.S.A. This suggests that there is potential for a vast amount of
      injuries and deaths to be eliminated if alcohol misuse could be controlled or
      eliminated.

PMID- 9257571
TI  - Research utilization.
AB  - The gap that persists between research and practice has been highlighted by nurse
      practitioners. In South Africa the research-practice gap is maximized by the lack
      of research facilities and research utilization projects in nursing education
      programmes. This paper considers conceptual, empirical and pragmatic issues in an
      attempt to explore the complexity of the influences that may affect the
      integration of research into nursing practice. Issues involved in a process of
      transferring research-based knowledge into innovative protocols for nursing
      practice are also dealt with.

PMID- 9257572
TI  - [Guidelines for the facilitation of wholeness in patients with AIDS: the
      experience of patients with AIDS: I].
AB  - AIDS will be remembered as the illness that was discovered in the 1980s of which
      the effects of this epidemic were only realised in the 1990s. Statistics show
      that the number of patients with AIDS increase annually because of the number of
      patients now diagnosed as HIV infected. Statistics indicate that AIDS has a much
      wider impact on the community than only homosexuals and drug-dependent people.
      Much attention is paid currently to the prevention of AIDS, but the problem is
      vested in the third phase of the HIV infection, namely AIDS. Nurses will be more
      and more exposed to the patient with AIDS and she can make a valuable
      contribution to facilitating the quest to wholeness of the patient with AIDS.
      This research was aimed at exploring and describing the experiences of the
      patient with AIDS and to lay down guidelines for the nurse and the psychiatric
      nurse specialist as consultant to facilitate the quest for wholeness of the
      patient with AIDS. A exploratory, descriptive contextual study was done with the
      aim of achieving insight into the experiences of the patient with AIDS, by way of
      a specific convenience test sample, five patients who complied with the set
      criteria were included in the research. The application possibilities of this
      research are generally set out as regards practice, research and teaching, and
      also as specific guidelines for the nurse treating the patient with AIDS. By
      following the guidelines set out in this research, the nurse can facilitate the
      patient's quest for wholeness.

PMID- 9257573
TI  - [Guidelines for the facilitation of wholeness in patients with AIDS: II].
AB  - In the previous article, Die belewenis van die pasient met VIGS: Deel I, better
      insight was obtained in the experiences of the patient with AIDS. In this article
      the focus is on the clinical application options of this research. Guidelines are
      set in this research to enable the nurse to facilitate the quest to wholeness of
      the patient with AIDS and the psychiatric nurse specialist to act as consultant
      for nurses who nurse the patient with AIDS in hospitals, nursing homes and at
      home.

PMID- 9257575
TI  - [The implications of various scientific-philosophical models on nursing].
AB  - This article focuses on the implications for nursing of philosophy of science.
      The relation between the dimensions of research in nursing, paradigms in nursing
      and the philosophy of science are explained as background. Models of philosophies
      of science are described, namely positivism, critical rationalism, Kuhn's
      historical approach, the phenomenological approach, hermeneutics, critical
      theory, scientific realism and post-modernism. The implications of each of these
      models are described within nursing as a science.

PMID- 9257574
TI  - The process-product dichotomy in education: relevance to nursing education.
AB  - Nursing education relies heavily on curriculum models originating in general
      education as a basis for curriculum design in nursing. As the content-product
      debate continues in general education, nurse educators will once again find
      themselves in a difficult situation of having to choose the best curriculum model
      in their efforts to reform nursing education. However, cognisance should be taken
      that whatever choices one makes, there are differences between professional
      education and general education. Although it might be appropriate for general
      education to choose a particular model because of its congruence with the
      curriculum designer's ideological views, many external forces impinge on
      professional education. Professional regulating bodies, the public and employers
      expect certain outcomes for professional education programmes. Nursing education
      programmes therefore should view the process and product models as alternatives
      rather than absolutes. There might be instances in which the process approach is
      suitable, whereas some programme aims might lend themselves perfectly to the
      product model.

PMID- 9257576
TI  - Psoriasis: experiencing a chronic skin disease.
AB  - Psoriasis is an incurable chronic skin disease that affects one in fifty people.
      Psychological factors play a role in the aetiology and experience of psoriasis
      but there is little pertaining to the psychological experience of psoriasis in
      research literature. In this study the phenomenological approach is used to
      describe the everyday experiences of a person with psoriasis. By using Giorgi's
      (1985) steps of data analysis a description of the lifeworld of the person with
      psoriasis was compiled. The description presented several essential components of
      the experience of psoriasis and the results emphasize the effects of the disease
      on the sufferer's life. Problematic interpersonal relationships, a negative
      selfconcept, fluctuating moods, loss of control, negativity and loneliness are a
      part of this experience. It is hoped that knowledge of the world of the psoriasis
      sufferer will assist the help professions to understanding and empathize with the
      suffering and limitations that psoriasis brings.

PMID- 9257578
TI  - The social support system of unmarried pregnant adolescents in the Transkei with
      particular reference to parents.
AB  - The purpose of this study was to investigate whether parental or other support
      systems supported the unmarried pregnant adolescent with regard to psychological
      and socio-economic parameters while they were pregnant, to determine the factors
      influencing support and to analyze the outcome of their pregnancy. Thirty rural
      and ten urban unmarried pregnant adolescents of 14-17 years of age were selected
      through quota sampling, therefore, 40 adolescents participated. Social support
      from significant others, as reported by adolescents, was measured through the
      Inventory of Socially Supportive Behaviour and Arizona Social Support Interview
      Schedule. The findings revealed that adolescents were given the support they
      needed, particularly by their mothers. Other family members, girlfriends and
      boyfriends also played a prominent role while support from professional support
      systems was minimal. Adolescent birth records indicate that most girls received
      prenatal care regularly. Most of their neonates were satisfactory at birth and
      were average for gestational age.

PMID- 9257577
TI  - [Participative management in nursing service].
AB  - The management style of the nursing service manager influences the facilitation
      of health, quality nursing care and quality work life of the nurses. No evidence
      of any research in this regard-within the context of nursing service-in South
      Africa could be found. The concept participative management, as well as the
      process (with applicable guidelines) therefore requires investigation. The
      purpose with this article is to isolate (identify and define) the central
      concepts pertaining to participative management in a nursing service, as well as
      the exploration and description of the process of participative management (with
      applicable guidelines). An exploratory, descriptive and qualitative research
      design was followed. Individual interviews with management experts were
      conducted. Content analysis of these interviews were done, as well as a
      literature control. A conceptual definition was formulated by inference of data,
      as well as the description of the process of participative management, with
      applicable guidelines. It is recommended that this definition be submitted to
      further refinement to form the foundation of a model for participative management
      in a nursing service. It will also be meaningful to research the costs and other
      implications related to participative management in a nursing service.

PMID- 9257579
TI  - Nursing service managers' views on problems they experience in their everyday
      lives: Part 1.
AB  - During 1994 it became clear to the health care delivery system management team of
      the old Transvaal region (Gauteng, North West and Eastern Transvaal) that nursing
      service managers in leadership positions were experiencing great strain in their
      daily work situation and seemed fatigued and stressed. The problem identified was
      that if nursing service managers themselves were fatigued and stressed, this
      would become an obstacle in the provision of quality health care. Assistance was
      requested to provide a support programme for the nursing service managers. Prior
      to developing and implementing the support programme it was necessary to explore
      and describe nursing service managers' views on the problems they were
      experiencing in their everyday lives (personal and professional) and to ascertain
      their specific needs for support. A qualitative, exploratory, descriptive and
      contextual research design was utilised in this research. A questionnaire with
      open-ended questions was used for gathering data. A purposive sample of one
      hundred nursing service managers was included in this research. Sixty of the one
      hundred questionnaires were completed. Data were analysed by a qualitative
      descriptive method of analysis. Four major categories regarding nursing service
      managers' experience of problems in their daily lives, were identified:
      difficulty in relationship with diverse others; lack of sufficient group
      acceptance/support; value conflicts, and difficulty with self-acceptance
      Conclusions and recommendations were made and limitations discussed.

PMID- 9257580
TI  - Nursing theory development.

PMID- 9257581
TI  - A profile of students who followed a course in the didactics of psychiatric
      nursing at Unisa during 1994.
AB  - Students who followed the above course did so as part of the Nursing Education
      III course offered at UNISA. This research aims at establishing a profile of
      these students. Aspects covered include age, sex, marital status, professional
      and academic qualifications, professional posts held and current fields of
      occupation. Such knowledge will clarify who the psychiatric nurse educators of
      the future might be, and also what the target population for the above course
      could be. Students' personal perceptions of the above course are sought in the
      second part of the questionnaire. Such information should be valuable in
      improving future courses for educators of psychiatric nurses.

PMID- 9257582
TI  - Non compliance with treatment schedules in chronic psychiatric patients.

PMID- 9257583
TI  - Expressed health education needs of black adults living in Ivory Park (Gauteng).
AB  - The overall aim of this study was to ascertain African male and female expressed
      needs for health education programmes. A random sample of 599 adults (229 males
      and 370 females over 15 years of age) from an informal settlement area (Ivory
      Park, Gauteng) was interviewed. Out of the 599 respondents, 467 (78%) said that
      they had received health education, usually through the radio or at a
      clinic/hospital. Ninety three per cent stated that they would like to receive
      health education; 52 topics were mentioned. Responses were grouped into six
      categories: AIDS (32%); Specific Diseases (31%); Child Health (13%); Family
      Planning (12%); General Health (10%); and Other (2%). Gender and age group were
      not related to health education category. Doctors and nurses were the preferred
      presenters of health education at a hospital, clinic or community health centre,
      through a talk or TV/Video. It was concluded that: (1) there was a definite need
      for health education, with a focus on AIDS, tuberculosis, child health and family
      planning; (2) men wanted to be involved in health education programmes; and (3)
      innovative delivery options need to be developed.

PMID- 9257584
TI  - Ethical standards for nurse researchers. SA Society for Nursing Researchers
      (SASNR).

PMID- 9257585
TI  - Breast-feeding: current knowledge, attitudes and practices of paediatricians and
      obstetricians.
AB  - OBJECTIVE: To assess the current knowledge, attitudes and practices of
      Paediatricians and Obstetricians in the greater Johannesburg area, using
      WHO/UNICEF 10 Steps to Successful Breastfeeding as a guideline. DESIGN: Survey.
      SUBJECTS: All Paediatricians and Obstetricians registered with the SAMDC and
      practising in the greater Johannesburg area. RESULTS: Most Paediatricians and
      Obstetricians advocate breastfeeding, but very few conform adequately to
      recommended guidelines. CONCLUSION: Doctors, as part of the healthcare team, can
      have a significant impact on the successful initiation and maintenance of
      breastfeeding. There is a need for ongoing education and intervention programmes
      to update current knowledge on breastfeeding management.

PMID- 9257586
TI  - [A video-based teacher educational and support program for first-year nursing
      students].
AB  - A video-based method of instruction was introduced to develop students
      academically as well as to implement parallel medium instruction. An action
      research approach was followed. Lectures were video-taped beforehand and worked
      through with the students by a tutor in scheduled Afrikaans or English periods.
      Simultaneously a live class situation was handled by the lecturer in the other
      language. Over and above these methods additional video-based support sessions
      were conducted by tutors for high risk students. A survey indicated that 85% of
      students were satisfied with this method of instruction. The perceptions of high
      risk students to VSI were positive and they passed the examinations. Video
      lectures need to be carefully planned in order to be acceptable as one of a
      number of possible instruction methods at a multi-cultural university.

PMID- 9257587
TI  - Development and operation of a support programme for nursing service managers:
      Part 2.
AB  - This paper describes research conducted to develop and implement a support
      programme for nursing service managers suffering from fatigue. The support
      programme was developed on the basis of results obtained from a survey that
      ascertained nursing service managers' views about the problems they were
      experiencing in their everyday lives. A multiple case-study design was utilised
      to describe the operationalisation of the support programme. The sample consisted
      of forty-eight English speaking and fifty-two Afrikaans speaking nursing service
      managers from the old Transvaal region (Gauteng, North West and Eastern
      Transvaal. The support programme was implemented during two one-day workshops,
      one with the Afrikaans speaking group and one with the English speaking group of
      nursing service managers. Data were gathered about operationalisation of the
      support programme through multiple methods: observation, audiotape recordings,
      written documents and field notes. The data were analysed by utilising the
      methods of descriptive analysis. The results of the research were described by
      means of multiple descriptive case-studies, whereafter a cross-validation report,
      as described by Yinn (1989:52-57) was utilised to reflect commonalities and
      differences between the workshops. Conclusions and recommendations were made and
      limitations discussed.

PMID- 9257588
TI  - Accessibility of professional health care (PRHC) in greater Bloemfontein.
AB  - The health of citizens is usually a priority in any society. In order to
      prevent/cure disease, people make use of various forms of care, ranging from lay
      care to professional health care (PRHC). Professional health care, however, is
      not equally accessible to all members of a society. This article attempts to
      indicate how factors such as costs, distance, consultation hours, attitude of
      medical personnel can result in PRHC being less accessible for some members and
      totally inaccessible for other members of a society. It is imperative that health
      care planners should once again review this issue in order to ensure that all
      South Africans are able to exercise their basic right to health care.

PMID- 9257589
TI  - [Dimensions of leadership practice by nursing service managers].
AB  - Leadership development is an important component of the nursing service manager's
      personal and professional development. Competent leadership is required to lead
      the nursing service in the right direction within the context of dynamic
      political and social changes. Various internal and external environmental
      variables have a significant influence on leadership behaviour and practice. The
      purpose with this study is to explore and describe the characteristics or
      dimensions of leadership excellence by the nursing service manager. An
      exploratory and descriptive research design was followed and data collection was
      done by means of focus group interviews. The results do not show a significant
      difference between the knowledge already generated by research, or described in
      the literature, but is utilised as the basis of leadership development of nursing
      service managers. A leadership development programme for nursing service
      managers, based on the results of this study, is recommended.

PMID- 9257590
TI  - The information needs of cancer patients in the Pretoria and Witwatersrand area.
AB  - More than 48,500 South Africans annually are confronted with the diagnosis of
      cancer. (Sitas, 1994) Judging from the literature it would seem that the
      acquisition of information about the various aspects of their disease is a very
      important coping mechanism for the cancer patient. Various studies concerning the
      information needs of cancer patients have been published in the USA, the UK and
      Australia. Similar studies have not yet been published in South Africa. In this
      article the information needs of cancer patients in South Africa are tabulated
      based upon research done for the fulfillment of requirements for a Masters degree
      in Information Studies at the Rand Afrikaans University. Information Services
      available to these patients are then also described in detail. Because of the
      sensitive nature of the subject questionnaires were compiled in co-operation with
      medical professionals who treat cancer patients. The questionnaire mainly
      concentrates on the physical and therapeutic aspects of the disease. Surgery,
      radiation therapy and chemotherapy are looked at. The research population
      consisted of 200 cancer patients who were receiving treatment at various
      treatment centres in the Pretoria-Witwatersrand area. The statistical processing
      of the results confirmed that the majority of the cancer patients need detailed
      information about the various aspects of their disease. For example more than 75%
      of respondents indicated that they would like to receive detailed information
      about reasons and possible side effects as well as ways of minimising the side
      effects of all the treatment methods ranging from diagnostic tests to surgery as
      well as radiotherapy and chemotherapy. Above 80% of respondents wanted to be
      informed about the possible success rate of surgery, radiation therapy and
      chemotherapy in their specific cancer. It is interesting to note that 78.5% of
      the respondents wished to be informed about the prognosis/survival rate of their
      specific cancer. The two preferred methods of communication indicated were
      firstly personal contact and then a combination of personal contact and booklets.
      An important conclusion which can be reached is that co-operation between the
      medical professionals, the information services and the patient and his family is
      essential if the information needs of the cancer patient are to be met
      satisfactorily.

PMID- 9257591
TI  - Psychiatric nursing research based on nursing for the whole person theory.
AB  - One of the determinants for decision-making in conducting psychiatric nursing
      research is the researchers' framework of reference he/she works from. This
      framework of reference refers to the way in which researcher views reality and is
      called a paradigm and consists of metatheoretical, theoretical and methodological
      assumptions. The metatheoretical assumptions reflect the researcher's view of a
      person, health, nursing and environment. These are beliefs and cannot be tested
      and are accepted to be true for the researcher. The theoretical assumptions are
      deducted from the metatheoretical assumptions and can be formulated into central
      statements or hypothesis and be validated through research. Nursing for the Whole
      Person Theory has a set of metatheoretical, theoretical and methodological
      assumptions that can provide direction in conducting psychiatric nursing
      research. In this paper the application of Nursing for the Whole Person Theory in
      conducting psychiatric nursing research will be demonstrated by using a completed
      psychiatric nursing research study as an example.

PMID- 9257592
TI  - The role of the community mental health nurse in Botswana: the needs and problems
      of carers of schizophrenic clients in the community.

PMID- 9257593
TI  - Self-directed learning in the context of a nursing curriculum: development of a
      learning plan.
AB  - The rapid pace at which biological health breakthroughs and advancements in
      technology occur is creating unique challenges to health care programmes. The
      curricula of all health care programmes will need to be set in learning
      environments where students will be able to develop learning skills that are
      transportable across situations, over a whole lifetime. This article attempts to
      focus on self-directed learning (SDL) concepts and the development of a learning
      contract/plan, including the roles of both the student and faculty in self
      learning approaches and contractual development.

PMID- 9257594
TI  - Levels of use of selected components of the comprehensive basic nursing
      programme.
AB  - Change in nursing education in South Africa has been characterised by the
      predominance of the use of power-coercive strategies to effect change. Changes in
      nursing curricula are legislated through the South African Nursing Council. The
      Comprehensive Basic Nursing Programme (CBNP) became mandatory for all
      institutions offering basic professional nurse preparation education programmes
      in this country in 1985. This was a comparative descriptive study aimed at
      examining the levels of use of 47 nurse educators at four nursing colleges
      regarding their behaviours and skills in implementing four selected components of
      the CBNP. The components of the CBNP which formed the focus for this study were
      teaching to produce nurses capable of (a) rendering comprehensive health care,
      (b) nursing holistically, (c) thinking critically, and (d) learning
      independently. The Levels of Use diagnostic dimension of the Concerns Based
      Adoption Model (CBAM) developed by the CBAM staff (Hall & Hord, 1987; Hall &
      Loucks, 1977, Hord, 1987; Loucks, Newlove, & Hall, 1975) was used as a guideline
      for designing the interview schedules for each of the four components of the
      CBNP. Data were collected by means of interviews using focused interview
      schedules designed by the researcher. A large number of nurse educators were
      rated at or below mechanical Level of Use on teaching for CHC (n = 26), and
      critical thinking (n = 22). More than half the nurse educators interviewed
      reported that they were comfortable with their behaviours and skills concerning
      teaching for holistic nursing and developing independence in learning.

PMID- 9257596
TI  - [Professional secrecy].
AB  - Confidentiality is a "sensitive" subject known to all professional nursing
      personnel. The perception of confidentiality in nursing students was determined
      during a research project. Some responses were surprising. The surprises were
      mostly due to the fast development in the medical and technology fields. These
      findings proved to be of significance in that guidelines for confidentiality are
      not up to date with the developments in these fields. These guidelines should be
      revised or rewritten to bring them up to date and help the professional nurse in
      decisions on aspects concerning confidentiality.

PMID- 9257595
TI  - [Nurses' and patients' experience of combined health service delivery to all
      population groups in a hospital].
AB  - In a community hospital in Gauteng, the hospital management had, on short notice,
      to provide combined health services to all population groups. In the past
      different health services were delivered to each population group. The
      integration of health service delivery was a sudden change. Based on this,
      research questions arose, namely: how do nurses and patients experience this
      change, and how could they be assisted to adjust to the change. The research
      objectives were twofold, namely: to explore and describe nurses and patients'
      experience of combined health delivery to all population groups and based on the
      results to make recommendations to assist them with adjustment to a combined
      health delivery system. An exploratory, descriptive and contextual research
      design was followed. Trustworthiness was ensured by applying Guba's approach.
      Phenomenological and individual focus interviews were conducted with forty nurses
      and patients who were selected purposively. Field notes were written after
      completion of each interview. The transcribed data was analysed by using Giorgi's
      and Kerlinger's methods combined. Results were discussed and a literature control
      completed. The most important conclusions reached were: there was an insufficient
      administrative structure in the hospital as a result of insufficient preparation
      for the combined health service delivery for all population groups; the whites'
      perception of different populations groups is based on an ethnocentric Western
      approach. This led to their experience of culture shock that resulted in feelings
      of anger/frustration, fear and sadness; the willingness of other populations
      groups to adjust to combined health service delivery led to their experience of
      happiness; there exists communication problems between population groups because
      of their not being able to communicate in their own language and the difference
      in communication styles; the verbalised Christian viewpoint and values of whites
      nurses and patients are not congruent with their prejudiced perception of people
      of other population groups and cultures, and the different population groups do
      not know each other's lifeworlds and that leads to prejudices that block open
      communication. Several recommendations were made based on these conclusions.

PMID- 9257597
TI  - Exit standards for the baccalaureate degree in nursing in South Africa.

PMID- 9257598
TI  - Attitudes of diploma-prepared and graduate registered nurses. Towards nursing
      models: a comparative study.
AB  - Currently, nursing theory is not a South African Nursing Council requirement for
      pre-registration nursing education curricula. AIM OF THE STUDY: to determine
      registered nurses' (RNs) attitudes towards nursing models. METHODOLOGY:
      replication of McKenna's (1994) 20-item Likert-type self-completion questionnaire
      with adaptations. RESEARCH SETTING: A 1,600-bedded State-funded academic hospital
      in Cape Town, South Africa. STUDY SUBJECTS: Two groups: RNs who had nursing
      degrees and RNs who had a traditional diploma training. FINDINGS: Results from
      the Mann-Whitney U-test for independent samples indicates that at the 0.05 level
      of significance there was no difference in how each group of RNs responded to 19
      statement items so there was not enough evidence to reject the Null Hypothesis
      for these statements (P < 0.05). However, as a group, the diploma-prepared RNs
      appeared to have a more positive attitude than the graduate RNs towards nursing
      models.

PMID- 9257599
TI  - [Curriculum evaluation as implemented by the Ann Latsky Nursing College].
AB  - Comprehensive curriculum evaluation, based on Roos's curriculum evaluation model,
      was completed at the Ann Latsky Nursing College. This project was planned and
      implemented by means of a curriculum evaluation plan. In this article, the
      authors discuss the methodology that was followed during curriculum evaluation
      and that can serve as a guideline for tutors from other colleges.

PMID- 9257600
TI  - The use of action research as an appropriate method of introducing and evaluating
      change in nursing care in an accident & emergency unit in Durban--Part 1.
AB  - This 2-part article discusses firstly, the general characteristics of action
      research, compares several strategies of approach and describes the author's
      chosen method of applying action research to particular aspects of nursing care
      in an Accident & Emergency Unit in a Durban hospital. The second part of the
      article (to be published in the next issue of Curationis) describes
      identification of problems within the unit, the implementation of change and the
      limitations and potential of such study to nursing practice.

PMID- 9257601
TI  - Job satisfaction and self-esteem of South African nurses.
AB  - The overall aim of this study was to investigate job satisfaction and self-esteem
      among South African nurses. The objectives of the study were to: (1) ascertain
      South African nurses' satisfaction with their work, pay, promotion, supervision
      and co-workers; (2) compare job satisfaction of South African nurses with that of
      North American nurses; (3) determine levels of self-esteem; and (4) test the
      direct and indirect effects of self-esteem on job satisfaction. A postal survey
      was conducted on a random sample of 2,000 nurses registered with the South
      African Nursing Council; 396 persons returned the questionnaires (Group 1). A
      subsample of 93 nonrespondents was traced and agreed to complete the
      questionnaire (Group 2). Minimal differences justified combining the groups and
      conducting subsequent analyses on total sample scores. Nurses were most satisfied
      with supervision and co-workers and least satisfied with promotion and pay.
      Reliability coefficients for the five job satisfaction subscales and overall
      scale ranged between 0.79 (work) and 0.93 (overall scale). South African nurses
      were significantly less satisfied with all aspects of their jobs than their
      American counterparts. Coefficient alpha for the self-esteem scale was 0.72, 0.87
      for the work-related needs scale and 0.80 for the social approval scale. High
      self-esteem nurses were more likely to attend to work-related needs in judging
      their job satisfaction than low self-esteem nurses. The best model for predicting
      job satisfaction was the linear incorporation of self-esteem and work-related
      needs. It was concluded that: (1) the Job Descriptive Index (JDI) was a useful
      measure of job satisfaction; (2) the quality of life in the South African nursing
      profession was lower than their American counterparts; (3) nurses had high levels
      of self-esteem; and (4) self-esteem directly and indirectly affected job
      satisfaction.

PMID- 9257602
TI  - An evaluation of the effect of programme changes in an acute psychiatric unit.
AB  - This article describes a research project in which nurses evaluated the effect of
      changes in a unit programme in a situation where staffing and other resources are
      severely limited. A quasi-experimental design was used in which the situation
      before the change was compared with the situation after implementation of the new
      programme. The dependent variables were patient symptoms and interaction patterns
      in the unit. The study was done in an acute female psychiatric inpatient unit in
      a large state psychiatric hospital in South Africa with predominantly black Zulu
      speaking patients. It was found that the changed programme did not increase the
      total interactions in the unit significantly, but that it did increase neutral
      interactions and decreased negative interactions. It also kept the rate of
      interaction steady over time between patients and staff and steadily increased
      interaction between patients themselves. In the control group all interactions
      decreased over time. No significant difference was found in symptoms between the
      two groups. It is concluded that the structured programme in a unit may change
      interaction patterns positively, even when poor staffing makes it possible only
      to plan nursing care for groups of patients rather than individuals. Whether
      these changes in interaction will be transferred to family and friends in the
      longer term, still has to be explored.

PMID- 9257603
TI  - The role of the unit sister in teaching student nurses in KwaZulu hospitals.
AB  - This study deals with the rate of the unit sister in teaching student nurses in
      KwaZulu hospitals. The aim of the study was to identify the extent of her
      involvement in managing the nursing unit to ensure clinical teaching and her
      involvement in the clinical teaching process. The role theory and the clinical
      teaching process formed the conceptual framework. Data was collected from 36
      sisters in charge of nursing units by means of a questionnaire. The results of
      the study indicated that: unit sisters regard good management of the unit as
      essential for effective clinical teaching; unit sisters regard clinical teaching
      as one of their important roles and functions as they said they were involved in
      all activities of the clinical teaching process. However, the responses were
      confined to what the unit sisters said they do which might not be what they
      actually do.

PMID- 9257604
TI  - [Service experience of community psychiatric nurses: 1].
AB  - Since psychiatric community services were legalised by the promulgation of the
      Mental Health Act no 18 of 1973 shift to primary mental Health Care has occurred.
      This change resulted in an increase in psychiatric patients within the community,
      and because of this increase the workload of the psychiatric community nurse
      became heavier. This higher expectation might cause pressure for the psychiatric
      community nurse and therefore influence her therapeutic relationship with her
      patient negatively. It was therefore important that the work experience of the
      psychiatric community nurse should be explored and described in order to
      formulate guidelines to mobilise resources to promote, maintain and restore the
      mental health of the psychiatric community nurse. A exploratory, descriptive
      contextual study was done with the aim of achieving insight into the internal
      environment experiences of the psychiatric community nurse working in the
      psychiatric community. In depth exploration was achieved by way of the
      phenomological method of interviewing to obtain data.

PMID- 9257605
TI  - Strikes by nursing personnel: a challenge for nurse managers in KwaZulu-Natal
      Province.
AB  - A descriptive survey was conducted to investigate strikes by nursing personnel as
      a challenge for nurse managers in KwaZulu-Natal Province. Data was collected from
      nurse managers and various categories of nursing personnel excluding student and
      pupil nurses. Results confirmed that patient care is adversely affected by
      nurses' strikes. There is division in opinions on the nurses' strikes. It is
      recommended that minimising or prevention of nurses' strikes should be a joint
      responsibility of all stakeholders in health care, that is employing authorities,
      management, nursing personnel and consumers of health care. Long term planning
      for continued, safe patient care during strikes should be given priority
      attention.

PMID- 9257606
TI  - Factors leading to black elderly persons' decisions to seek institutional care in
      a home in the Eastern Cape.
AB  - The experience of leaving home by an elderly person and going into an institution
      for the elderly is viewed by many people as a stressful situation that needs
      support not only for the elderly but also for the family members that are left
      behind. A qualitative study was conducted at a home for the elderly in the
      Eastern Cape Province with the aim of exploring factors that result in a decision
      to seek institutional care. The study used in-depth individual semi-structured
      interviews as a method of data collection. The target population consisted of 200
      elderly people in the institution. Twelve respondents were interviewed in this
      study. The interviews were recorded and later transcribed verbatim. The data were
      analyzed using Vankaam's method of content analysis. The results revealed four
      types of factors as: physical, psychological, psychosocial and social. It also
      became clear that elderly people's past experiences correlated significantly with
      their decision concerning institutionalization. The recommendations pointed to
      the utilization of institutions for the elderly as rehabilitation centres as
      opposed to nursing homes or old folk's homes. The implications for the role of
      both community health nurses and psychiatric nurses concerning screening and
      counselling of those elderly people who could still be returned to their homes
      were highlighted. Further research was recommended in the form of developing a
      model to base gerontological practice in this country with regards to
      institutionalization.

PMID- 9257607
TI  - Perception of AIDS by Esikhawini Community.
AB  - This study was undertaken to assess the perception of AIDS by Esikhawini
      Community in KwaZulu Natal. The assumption was that the more health education is
      given to the community, the more knowledgeable the community becomes. The study
      revealed that the community is aware of AIDS. Sufferers pose a challenge to
      health workers as talks by health units ranked third in the sources contributing
      to the knowledge about AIDS. A descriptive cross sectional survey design was used
      and the questionnaire had both closed and open ended questions.

PMID- 9257608
TI  - Accident analysis in a busy surgical ward.

PMID- 9257609
TI  - Views of mothers concerning prolonged hospitalisation because of low birth weight
      infants.

PMID- 9257610
TI  - Reasons women give for refusing tubal ligation.

PMID- 9257611
TI  - Participatory research in psychiatric nursing.

PMID- 9257612
TI  - Psychiatric nursing research based on nursing for the whole person theory.
AB  - One of the determinants for decision-making in conducting psychiatric nursing
      research is the researchers' framework of reference he/she works from. This
      framework of reference refers to the way in which researcher views reality and is
      called a paradigm and consists of metatheoretical, theoretical and methodological
      assumptions. The metatheoretical assumptions reflect the researcher's view of a
      person, health, nursing and environment. These are beliefs and cannot be tested
      and are accepted to be true for the researcher. The theoretical assumptions are
      deducted from the metatheoretical assumptions and can be formulated into central
      statements or hypothesis and be validated through research. Nursing for the Whole
      Person Theory has a set of metatheoretical, theoretical and methodological
      assumptions that can provide direction in conducting psychiatric nursing
      research. In this paper the application of Nursing for the Whole Person Theory in
      conducting psychiatric nursing research will be demonstrated by using a completed
      psychiatric nursing research study as an example.

PMID- 9257613
TI  - Assessment of a Xhosa psychiatric patient using the transcultural approach.

PMID- 9257615
TI  - AADE legislative advocacy: perspectives on prevention.

PMID- 9257614
TI  - Maintaining scientific integrity in publications.

PMID- 9257616
TI  - Strategies for overcoming barriers to healthcare utilization: Part II.

PMID- 9257617
TI  - Sugar-free medications.

PMID- 9257618
TI  - Fear of hypoglycemia in the parents of children and adolescents with diabetes:
      maladaptive or healthy response?
AB  - Sixty-one parents of children with insulin-dependent diabetes mellitus completed
      modified versions of the Hypoglycemic Fear Survey (HFS) and the Diabetes Quality
      of Life (DQOL) scale. They also indicated their child's history of hypoglycemic
      related seizures or loss of consciousness (SLC) events. Parental HFS scores were
      significantly greater if their child had ever experienced a SLC event or
      experienced a SLC event within the past year. Parental HFS scores were positively
      correlated with general parental worry about their child having diabetes.
      Adolescent children who experienced a SLC event during the past year reported
      greater HFS scores, greater general worry about diabetes, and a greater negative
      impact of having diabetes compared with adolescents with no such history. Despite
      the greater fear of hypoglycemia in parents and adolescents, there was no
      significant difference in HbA1 values between children with or without any
      history of SLC events or children with or without a SLC event within the past
      year.

PMID- 9257619
TI  - Telephone communications between diabetes clients and nurse educators.
AB  - The purpose of this study was to describe the use of telephone communications
      between diabetes nurse educators (DNEs) and their clients with diabetes. A
      questionnaire was designed to examine the use of the telephone with diabetes
      clients from the perspective of DNEs. A total of 465 DNEs across the US were
      selected using a systematic sample from the membership directory of the American
      Association of Diabetes Educators. A total of 247 were questionnaires completed
      and returned (55%). Ninety-one percent of DNEs reported using the phone with
      clients and averaged 15 phone calls per week. Over 90% frequently reported
      discussing the following topics with clients: home blood glucose monitoring,
      hyperglycemia, hypoglycemia, insulin use, and diet. Analysis of telephone users
      showed that DNE experience and diabetes educator certification were significant
      factors in the differences observed in the reported topics discussed over the
      telephone. These findings suggest the need for guidelines for telephone contact
      with diabetes clients.

PMID- 9257620
TI  - Do sociodemographics and economic status predict risks for type II diabetes in
      African Americans?
AB  - The prevalence of type II diabetes and the metabolic characteristics in high-risk
      African Americans were examined to determine whether certain socioeconomic and
      demographic characteristics (SED) increase the risk for type II diabetes in this
      population. Study participants were high-risk African Americans between the ages
      of 25 and 64 years. Glucose tolerance status was assessed and questionnaires were
      completed to obtain information regarding SED, hypertension, and physical
      activity. The majority of patients had normal glucose tolerance; undiagnosed type
      II diabetes was identified in 36 of 164 patients. Questionnaire data revealed
      that, in highly selected African Americans at risk for type II diabetes, there
      was a higher rate of obesity, prior gestational diabetes, and undiagnosed type II
      diabetes despite higher educational and income levels and greater access to
      health care and recreational facilities. Findings indicate that African Americans
      may be at higher risk for type II diabetes, regardless of socioeconomic status,
      due to genetic inheritance and other unknown environmental determinants. Further
      studies are needed to characterize SED and metabolic profiles that confer a high
      risk for type II diabetes in this population.

PMID- 9257622
TI  - The case management paradox.

PMID- 9257621
TI  - Diabetes in urban African Americans. Body image, satisfaction with size, and
      weight change attempts.
AB  - We developed two gender specific sets of body-size silhouettes for evaluating
      body image in African Americans; 370 clinic-based adult participants with
      diabetes were queried on body image, perceptions, current efforts to change
      weight, and psychosocial variables. Comparisons were made by weight group and sex
      after classification as overweight or not overweight according to body mass index
      (BMI). Regardless of sex or weight category, perceived current body size was
      significantly related to BMI. Both men and women who were classified as
      overweight selected a desired body size that was significantly smaller than their
      perceived current size. Men, however, were more likely than women to select a
      larger desired size relative to their current size. Both men and women expected
      the dietician to favor a body size smaller than their own desired size and felt
      their designated important adult would choose the same desired size that they
      selected. Given the importance of cognitive perspectives in understanding weight
      management, it may be useful to incorporate body image measures into both
      observational and interventional studies.

PMID- 9257623
TI  - Consumer-directed home care: client profiles and service challenges.
AB  - This article presents the results of a study that sought to develop a profile of
      potential consumer-directed clients in a countywide home care program. In order
      to develop this profile, clients were assessed by the telephone case manager and
      the in-home assessor, each of whom made an independent decision about the
      appropriate level of case management for the client. Of the 278 clients assessed,
      16.5% were identified by both professionals as candidates for consumer-directed
      care; for another 42.1%, the case manager and assessor agreed that a more intense
      level of care was appropriate. For the remaining clients (41.4%), there was
      disagreement between the two assessments about the appropriate level of case
      management. Clients identified as consumer-directed candidates were more likely
      to be female, to have fewer impairments, to receive fewer services, to have low
      incomes, and to live alone. Case managers' and assessors' comments indicated that
      the consumer-directed group consisted of those more likely to have stable health
      and a good support system, along with an understanding of the service system and
      a willingness to make contacts in case of problems or status changes. The article
      also explores the implications for service providers.

PMID- 9257624
TI  - Paying family members to provide home care: an evaluation of one program.
AB  - Paying family members for caregiving has received mixed reviews, but most agree
      that elders tend to prefer community to institutional living. This study
      describes an evaluation of a program that paid family caregivers to provide home
      care to elders from the perspective of care receivers (n = 151), caregivers (n =
      211), and case managers (n = 71). The care recipients were primarily older, low
      income individuals who were assessed to be at medium to high risk with respect to
      psychosocial functioning. Results indicated that caregiver subsidies were
      primarily used to pay for basic necessities, but few caregivers would cease
      caregiving in the absence of subsidies. The vast majority of care receivers and
      caregivers were very satisfied with case management services, and 42% of the care
      receivers named their case manager when asked whom they would contact if they had
      a problem with their caregiver. Case managers stressed the importance of formal
      care providers making home visits and referrals to other resources in order to
      lessen isolation and prevent institutionalization.

PMID- 9257625
TI  - A model gatekeeper program to find the at-risk elderly.
AB  - This article describes the client characteristics and services needs of community
      dwelling older adults found through a unique case-finding model developed at the
      Spokane Mental health Center. The model trains the employees of community
      businesses and corporations who work with the public to serve as community
      gatekeepers by identifying and referring community-dwelling older adults who may
      be in need of aging and/or mental health services. These community case-finders
      perform a gatekeeping function for older adults that is similar to that performed
      by schools and the workplace for younger persons. Information was collected on
      777 individuals aged 60 and older referred over an 18-month period (January 1,
      1994, to June 30, 1995) to the Spokane Mental Health Clinical Case Management
      Program in Spokane, Washington, which provides aging and mental health services
      to older adults residing in the county. Findings indicate that 40% of clients
      referred were found by community-based gatekeepers. Clients referred by
      gatekeepers were more frequently socially isolated, economically disadvantaged,
      and less likely to have a physician. Gatekeeper clients were also more likely to
      be women and to be younger than others referred to the agency. Gatekeeper clients
      were receiving fewer services at referral and were identified as needing more
      services at intake. Gatekeepers find a distinct population of community-dwelling
      older adults who are not found by more traditional referral sources. The need to
      integrate this model within a comprehensive clinical case management system is
      discussed.

PMID- 9257626
TI  - Attorney-case manager collaboration in the conservatorship of older adults.
AB  - The complex issues of long-term care are everchanging, with no one discipline
      having the corner on all the intricate options, regulations, and ethical choices
      that often confront an aging person. This is most critical when a person's
      incompetence requires the appointment of a conservator or guardian. When the
      probate court finds it necessary to appoint a conservator/guardian for an older
      adult, and family or other informal caregivers are unavailable or unable to
      assume the role, the responsibility is often delegated to an attorney. However,
      an attorney's expertise is in the field of law, not necessarily in the complex
      and intricate long-term health care system. Maintaining a mentally incompetent
      and functionally disabled person in the safest and least restrictive environment
      is demanding. It requires a thorough knowledge and understanding of the physical
      and emotional changes associated with the aging process, an area of expertise of
      long-term care case managers. Combining the clinical proficiency of the case
      manager with the legal and financial expertise of the attorney benefits the
      conserved older adult. This article illustrates this collaborative approach to
      long-term care through the use of several case histories.

PMID- 9257627
TI  - The advanced practice nurse as case manager.
AB  - The dynamic interactions of the client, service provided, and payer are complex
      relationships in today's health care environment. An advanced practice nurse's
      abilities to care physically and psychosocially for clients and their families
      are essential within the case management framework. With a holistic view of
      clients' health status, the nurse case manager develops and carries out advanced
      practice functions that help achieve the best outcome for the client through
      effective interactions with clients, payers, and providers. Those functions,
      illustrated by the Star Case Management Model, include interpretation, advocacy,
      and surveillance.

PMID- 9257628
TI  - Build partnerships: child/adolescent psychiatric nurses joining with families of
      children and adolescents with neurobiological disorders.

PMID- 9257629
TI  - Determinants of binge drinking and alcohol use by young Australian women.
AB  - PROBLEM: There is little empirical research concerning the role and culture of
      drinking behavior of young women. METHODS: 1,441 female high school students
      responded to a survey questionnaire containing quantity frequency measures of
      alcohol consumption and two sex roles scales. The Australian Sex Role Scale and
      the Women in Society Questionnaire. FINDINGS: Frequency of heavy drinking
      behaviors such as bingeing and getting drunk were a common occurrence. Levels of
      alcohol consumption and patterns of bingeing and getting drunk were related to
      the respondents frequency of drinking. Comparison between the two sex role scales
      and drinking behavior revealed that frequent and heavy drinkers were more likely
      to have masculine type personality traits and more liberal and contemporary views
      on the role of women in society. CONCLUSIONS: Young women who do not conform to
      traditional sex role stereotyping are likely to engage in what is considered to
      be risky health behaviors that have traditionally been associated with males.

PMID- 9257630
TI  - Female adolescent response to childhood sexual abuse.
AB  - PROBLEM: History of childhood sexual abuse has been linked to fear, anxiety,
      depression, aggression, anger, hostility, poor self-esteem, substance abuse, and
      sexual maladjustment, as well as somatic complaints. The purpose of this study
      was to compare sexually abused adolescent females to adolescent females who have
      not ben sexually abused with respect to incidence of emotional disorders and
      somatic symptoms. METHODS: A convenience sample of females, ages 12-17, included
      11 identified victims of sexual abuse and 11 nonabused adolescents. A descriptive
      design using multiple methods of data collection: interview questions, self
      report questionnaires, and projective drawings. FINDINGS: The sexually abused
      adolescents scored significantly higher than the adolescents who had no history
      of sexual abuse on specific sub scales (anxiety, muscle tension, cognitive
      disorganization) and on the total scale scores of both the SOS and the SCL-90.
      CONCLUSIONS: Given the epidemic proportions of childhood sexual abuse, nurses in
      varied settings are in a position to identify, evaluate, and treat families with
      adolescents who manifest a wide range of sequelae.

PMID- 9257631
TI  - Runaway youths in a southern community: four critical areas of inquiry.
AB  - PROBLEM: Significant life events in runaway youth include the experience of
      abuse, school/legal entanglements, and sexual behavior. SUBJECTS: 78 nonurban,
      runaway youths. METHODS: The Structural Clinical Interview Instrument and the
      Coddington Life Events Scale were used for data collection. FINDINGS: The
      majority of respondents reported life situations replete with experiences of
      abuse, school/legal entanglements, high-risk sexual behavior, and significant
      life events. Significant gender differences were reported regarding sexual
      activity (p = .002). Significant positive associations exist between the use of
      birth control and sexual activity (p = .002), and between school suspensions and
      sexual activity (p = .01). A significant relationship exists between the use of
      birth control and the occurrence of abuse (p = .01). CONCLUSIONS: Much research
      is needed to develop programs with a focus on prevention.

PMID- 9257632
TI  - Food allergies, asthma, and attention deficit hyperactivity disorder.

PMID- 9257634
TI  - Cover story: how it all began....

PMID- 9257633
TI  - Challenge? Accusation?

PMID- 9257637
TI  - Ergonomics research: impact on injuries.

PMID- 9257636
TI  - Medication errors: a recent case review.

PMID- 9257638
TI  - Profile of an NAPNES member.

PMID- 9257639
TI  - "Math made easy for nurses".

PMID- 9257640
TI  - History of NAPNES.

PMID- 9257641
TI  - Interaction of thiostrepton with an RNA fragment derived from the plastid-encoded
      ribosomal RNA of the malaria parasite.
AB  - Although eukaryotes are not generally sensitive to thiostrepton, growth of the
      human malaria parasite Plasmodium falciparum is severely inhibited by the drug.
      The proposed target in P. falciparum is the ribosome of the plastid-like
      organelle (35 kb circular genome) of unknown function. Positive identification of
      the drug target would confirm that the organelle is essential for blood-stage
      development of Plasmodium and help clarify the plastid's biological role. The
      action of thiostrepton as an antibiotic relates to its affinity for a conserved
      domain of eubacterial rRNA. Its effect on organelles is unknown. Because a number
      of different point mutations within the Escherichia coli domain abrogates
      thiostrepton binding, extensive sequence differences between eubacterial and
      plastid domains brings into question the site of drug action. We have examined
      temperature-dependent hyperchromicity profiles of synthetic RNAs corresponding to
      domains in the plastid and cytoplasmic RNAs of P. falciparum. Thiostrepton
      induces a tertiary structure in the plastid-like fragment similar to that seen in
      eubacterial rRNA, even though the two share only about 60% sequence identity. A
      single point mutation in the plastid-like fragment removes thiostrepton-dependent
      tertiary structure formation. Thus, the plastid and eubacterial RNAs share a
      stabilized tertiary structure induced by the drug. This direct indicator of drug
      sensitivity in eubacteria suggests that the plastid-encoded ribosome is similarly
      sensitive to thiostrepton and that the plastid is the site of drug action.
      Correlation of thiostrepton-sensitive and -resistant phenotypes with physical
      parameters suggests thiostrepton resistance as a selectable marker for plastid
      transformation.

PMID- 9257642
TI  - Insertional editing in isolated Physarum mitochondria is linked to RNA synthesis.
AB  - The mitochondrial RNAs of Physarum polycephalum are edited efficiently by
      nucleotide insertion both in vivo and in isolated mitochondria. Our recent
      studies have demonstrated that nucleotide addition can occur within 14-22 nt of
      the 3' end of a nascent RNA, suggesting that insertional editing may be linked to
      transcription. To investigate the relationship between these processes, we have
      examined the effects of nucleotide concentration on templated and nontemplated
      nucleotide addition in isolated mitochondria. At very low CTP concentrations,
      transcription and editing proceed with high fidelity, but the efficiency of
      cytidine insertional editing decreases. Insertion of single uridine and
      dinucleotides is not diminished under conditions that yield unedited or partially
      edited C insertion sites, indicating that editing events occur independently of
      one another. Moreover, analysis of partially edited RNA demonstrates that single
      nucleotides can be added at dinucleotide insertion sites. Importantly, pulse
      chase experiments indicate that nontemplated nucleotides are not inserted into
      previously synthesized RNA once editing conditions are restored, although RNA
      downstream of the unedited region is edited efficiently. This result indicates
      that insertional editing cannot occur posttranscriptionally under these
      conditions, and suggests that there is only a small "window of opportunity" in
      which nucleotide insertion can occur. Our data are consistent with an editing
      activity that functions in a strictly 5' to 3' direction and adds nucleotides at,
      or close to, the 3' end of nascent RNA in association with the transcription
      complex. Several possible models for the mechanism of insertional editing in
      Physarum are discussed.

PMID- 9257643
TI  - An RNA internal loop acts as a hinge to facilitate ribozyme folding and
      catalysis.
AB  - RNA molecules commonly consist of helical regions separated by internal loops,
      and in many cases these internal loops have been found to assume stable
      structures. We have examined the function and dynamics of an internal loop,
      J5/5a, that joins the two halves of the P4-P6 domain of the Tetrahymena self
      splicing group I intron. P4-P6 RNAs with mutations in the J5/5a region showed
      nondenaturing gel electrophoretic mobilities and levels of Fe(II)-EDTA cleavage
      protection intermediate between those of wild-type RNA and a mutant incapable of
      folding into the native P4-P6 tertiary structure. Mutants with the least
      structured J5/5a loops behaved the most like wild-type P4-P6, and required
      smaller amounts of Mg2+ to rescue folding. The activity of reconstituted introns
      containing mutant P4-P6 RNAs correlated similarly with the nature of the J5/5a
      mutation. Our results suggest that, in solution, the P4-P6 RNA is in a two-state
      equilibrium between folded and unfolded states. We conclude that this internal
      loop mainly acts as a flexible hinge, allowing the coaxially stacked helical
      regions on either side of it to interact via specific tertiary contacts. To a
      lesser extent, the specific bases within the loop contribute to folding.
      Furthermore, it is crucial that the junction remain unstructured in the unfolded
      state. These conclusions cannot be derived from a simple examination of the P4-P6
      crystal structure (Cate JH et al., 1996, Science 273:1678-1685), showing once
      again that structure determination must be supplemented with mutational and
      thermodynamic analysis to provide a complete picture of a folded macromolecule.

PMID- 9257644
TI  - Dynamics of RNA-protein interactions in the HIV-1 Rev-RRE complex visualized by 6
      thioguanosine-mediated photocrosslinking.
AB  - Expression of the structural proteins of human immunodeficiency virus type 1 (HIV
      1) requires the direct interaction of multiple copies of the viral protein Rev
      with its target RNA, the Rev response element (RRE). RRE is a complex 351-nt RNA
      that is highly structured and located within the viral env gene. During initial
      Rev-RRE recognition, Rev binds with high affinity to a bubble structure located
      within the RRE RNA stem-loop II. We have used a site-specific photocrosslinking
      method based on 6-thioguanosine (6-thioG) photochemistry to probe the
      conformation of the high-affinity binding site of RRE RNA and its interactions
      with Rev protein under physiological conditions. A minimal duplex RNA containing
      the bubble region of RRE and 12 flanking base pairs was synthesized chemically.
      Two different RRE constructs with a single photoactive nucleoside (6-thio-dG or 6
      thioG) at position 47 or 48 were synthesized. Upon UV irradiation, 6-thioG at
      both positions formed interstrand covalent crosslinks in RRE RNA. Mapping of
      crosslink sites by RNA sequencing revealed that 6-thioG at position 47 or 48
      crosslinked to A73. In the presence of Rev, both RNA-RNA and RNA-protein
      crosslinks were observed, however, the RNA-RNA crosslink site was unchanged. Our
      results provide direct evidence that, during RNA-protein recognition, Rev is in
      close proximity to O6 of G47 and G48 in the major groove of RRE RNA. Our results
      also show that the bubble region of RRE RNA has a biologically relevant structure
      where G47 and G48 are in close proximity to A73 and this RNA structure is not
      changed significantly upon Rev binding. We propose that Rev protein recognizes
      and binds to specific structural elements of RRE RNA containing non-Watson-Crick
      base pairs and such structures could be a determinant for recognition by other
      RNA-binding proteins. Our site-specific crosslinking methods provide a general
      approach to capture dynamic states of biologically relevant RNA structures that
      are otherwise missed by NMR and X-ray crystallographic studies.

PMID- 9257645
TI  - Functional group substitutions of the branchpoint adenosine in a nuclear pre-mRNA
      and a group II intron.
AB  - Splicing of nuclear mRNA precursors (pre-mRNAs) takes place in the spliceosome, a
      large and complex ribonucleoprotein. Nuclear pre-mRNA splicing and group II
      intron self-splicing occur by a chemically identical pathway involving
      recognition of a specific branchpoint adenosine and nucleophilic activation of
      its 2'-hydroxyl group. The chemical similarity between these two splicing
      reactions, as well as other considerations, have suggested that the catalytic
      core of the spliceosome and group II introns may be related. Here we test this
      hypothesis by analyzing splicing and RNA branch formation of a pre-mRNA and a
      group II intron in which the branchpoint adenosine was substituted with purine
      base analogues. We find that replacement of the branchpoint adenosine with either
      of two modified adenosine analogues or guanosine leads to remarkably similar
      patterns of splicing and RNA branch formation in the two systems.

PMID- 9257646
TI  - Translational misreading: mutations in translation elongation factor 1alpha
      differentially affect programmed ribosomal frameshifting and drug sensitivity.
AB  - The translation elongation feactor 1alpha (EF-1alpha) catalyzes the critical step
      of delivering aminoacyl-tRNAs to the elongating ribosome. A series of
      Saccharomyces cerevisiae strains containing mutant alleles of the TEF2 gene
      encoding EF-1alpha have phenotypes consistent with effects on cellular processes
      related to translation. These include (1) conditional growth defects, (2)
      antibiotic sensitivity or resistance, (3) altered +1 or -1 ribosomal
      frameshifting efficiencies, and (4) altered maintenance of the killer phenotype.
      Although all the mutant alleles were isolated as dominant +1 frameshift
      suppressors, the effects of these mutations on the cell are quite different when
      present as the only form of EF-1alpha. Allele-specific effects are observed with
      regard to their ability to alter the efficiency of programmed +1 frameshifting as
      opposed to programmed -1 ribosomal frameshifting. The significantly altered
      efficiency of -1 frameshifting in strains containing the TEF2-4 and TEF2-9 mutant
      alleles further correlates with a reduced ability to maintain the killer
      phenotype and the M1 satellite virus of L-A, an in vivo assay of translational
      fidelity. In light of the proposed models regarding the different A- and P-site
      occupancy states required for +1 or -1 ribosomal frameshifting, these results aid
      analysis of interactions between EF-1alpha and the translational apparatus.

PMID- 9257647
TI  - Two functional complexes formed by KH domain containing proteins with the 5'
      noncoding region of poliovirus RNA.
AB  - The 5' noncoding region of the poliovirus genome contains RNA structures
      important for replication and translation. Here we show that two closely related
      cellular poly(rC) binding proteins (PCBP1 and PCBP2) bind to the terminal
      cloverleaf structure and facilitate the interaction of the viral protein 3CD (the
      uncleaved precursor of the protease-polymerase). In addition, these cellular
      proteins bind to stem-loop IV of the internal ribosomal entry site. The proteins
      are cytoplasmic and largely associated with ribosomes; they appear to dimerize in
      solution and to form heterodimers when binding to stem-loop IV. Initiation of
      viral translation in Xenopus oocytes is strongly inhibited by co-injection of
      specific antibodies directed against PCBP1 or PCBP2, indicating that the poly(rC)
      binding proteins may facilitate this process. Furthermore, PCPB-depleted HeLa
      extracts translate poliovirus RNA inefficiently and the activity is partially
      restored by addition of recombinant PCBP proteins.

PMID- 9257648
TI  - Structure and aminoacylation capacities of tRNA transcripts containing
      deoxyribonucleotides.
AB  - The contribution of the ribose 2'-hydroxyls to RNA structure and function has
      been analyzed, but still remains controversial. In this work, we report the use
      of a mutant T7 RNA polymerase as a tool in RNA studies, applied to the aspartate
      and methionine tRNA aminoacylation systems from yeast. Our approach consists of
      determining the effect of substituting natural ribonucleotides by
      deoxyribonucleotides in RNA and, thereby, defining the subset of important 2'
      hydroxyl groups. We show that deoxyribose-containing RNA can be folded in a
      global conformation similar to that of natural RNA. Melting curves of tRNAs,
      obtained by temperature-gradient gel electrophoresis, indicate that in deoxyribo
      containing molecules, the thermal stability of the tertiary network drops down,
      whereas the stability of the secondary structure remains unaltered. Nuclease
      footprinting reveals a significant increase in the accessibility of both single-
      and double-stranded regions. As to the functionality of the deoxyribose
      containing tRNAs, their in vitro aminoacylation efficiency indicates striking
      differential effects depending upon the nature of the substituted
      ribonucleotides. Strongest decrease in charging occurs for yeast initiator
      tRNA(Met) transcripts containing dG or dC residues and for yeast tRNA(Asp)
      transcripts with dU or dG. In the aspartate system, the decreased aminoacylation
      capacities can be correlated with the substitution of the ribose moieties of U11
      and G27, disrupting two hydrogen bond contacts with the synthetase. Altogether,
      this suggests that specific 2'-hydroxyl groups in tRNAs can act as determinants
      specifying aminoacylation identity.

PMID- 9257649
TI  - Purpuromycin: an antibiotic inhibiting tRNA aminoacylation.
AB  - Purpuromycin, an antibiotic produced by Actinoplanes ianthinogenes, had been
      reported previously to inhibit protein synthesis. In the present report, we
      demonstrate that the mechanism of action of this antibiotic is quite novel in
      that it binds with fairly high affinity to all tRNAs, inhibiting their acceptor
      capacity. Although more than one molecule of purpuromycin is bound to each tRNA
      molecule, the inhibitory activity of this antibiotic was found to be selective
      for the tRNA acceptor function; in fact, after the aminoacylation step,
      purpuromycin was found to affect none of the other tested functions of tRNA
      (interaction with the ribosomal P- and A-sites and interaction with translation
      factors). Accordingly, purpuromycin was found to inhibit protein synthesis only
      when translation depended on the aminoacylation of tRNA and not when the system
      was supplemented with pre-formed aminoacyl-tRNAs. Because purpuromycin did not
      interfere with the ATP-PPi exchange reaction of the synthetase or with the
      initial interaction of the enzyme with its tRNA substrate, the basis for the
      inhibition of aminoacylation is presumably the formation of a nonproductive
      synthetase-tRNA complex in the presence of purpuromycin in which the tRNA is
      unable to be charged with the corresponding amino acid.

PMID- 9257650
TI  - Examination of the catalytic fitness of the hammerhead ribozyme by in vitro
      selection.
AB  - We have designed a self-cleaving ribozyme construct that is rendered inactive
      during preparative in vitro transcription by allosteric interactions with ATP.
      This allosteric ribozyme was constructed by joining a hammerhead domain to an ATP
      binding RNA aptamer, thereby creating a ribozyme whose catalytic rate can be
      controlled by ATP. Upon purification by PAGE, the engineered ribozyme undergoes
      rapid self-cleavage when incubated in the absence of ATP. This strategy of
      "allosteric delay" was used to prepare intact hammerhead ribozymes that would
      otherwise self-destruct during transcription. Using a similar strategy, we have
      prepared a combinatorial pool of RNA in order to assess the catalytic fitness of
      ribozymes that carry the natural consensus sequence for the hammerhead. Using in
      vitro selection, this comprehensive RNA pool was screened for sequence variants
      of the hammerhead ribozyme that also display catalytic activity. We find that
      sequences that comprise the core of naturally occurring hammerhead dominate the
      population of selected RNAs, indicating that the natural consensus sequence of
      this ribozyme is optimal for catalytic function.

PMID- 9257652
TI  - Quantitation of HIV-1-specific IgG, IgA, and IgM antibodies in human genital
      tract secretions.
AB  - A quantitative enzyme-linked immunosorbent assay (ELISA) has been developed for
      the quantitation of HIV-1-specific immunoglobulins of the IgG, IgA, and IgM
      isotypes and was used to assess HIV-specific antibody concentrations in semen and
      cervicovaginal lavage (CVL) specimens. Immunoglobulin isotype concentrations were
      assessed by capture ELISA using immunoglobulin isotype-specific secondary
      antibodies and commercial IgG, IgA, and IgM standards. HIV-1 antibody detection
      kits (Abbott Laboratories, North Chicago, IL, U.S.A.) and immunoglobulin isotype
      specific secondary antibodies were used to obtain optical density (OD) units for
      HIV-1-specific antibodies of each isotype. To determine the antibody
      concentrations from the OD values, ODs were compared with those from HIV-1
      specific antibody isotype standards of known concentration obtained from CVL
      specimens of seropositive women by affinity binding to HIV antigen-coated beads
      and acid elution. The sensitivity of the HIV-1-specific immunoglobulin assay was
      0.01 microg/ml for IgG, 0.04 microg/ml for IgA, and 0.08 microg/ml for IgM. The
      interassay coefficient of variation for the different immunoglobulin isotypes
      varied from 5% to 33%, being lowest for IgG and highest for IgM. HIV-1-specific
      antibodies were detected in all semen samples from seropositive men in
      concentrations ranging from 53 to 261 microg/ml. Thirteen of 14 samples contained
      high levels of HIV-1-specific IgG antibodies (22-72 microg/ml) whereas 10 of the
      14 (71%) semen samples contained detectable but lower levels of HIV-1-specific
      IgA and IgM (maximum level: 3.7 microg/ml for IgA and 14.8 microg/ml for IgM).
      HIV-1-specific IgG antibodies were detected in all 196 CVL samples from
      seropositive women in concentrations ranging from 0.01 to 47 microg/ml, whereas
      only 16 women (8%) had IgA levels above the detectable limit (range, 1.4-3.9
      microg/ml), and only eight women (4%) had IgM levels above the detectable limit
      (range, 1.8-8.6 microg/ml). None of 80 low-risk women or 20 low-risk men
      (negative controls) had detectable levels of HIV-1-specific antibodies in genital
      tract specimens. HIV-1-specific IgG levels in CVL specimens of seropositive women
      were significantly higher in individuals who had acquired HIV through
      heterosexual transmission, and a majority of women with elevated levels of HIV
      specific IgA isotype antibodies in CVL samples had evidence of genital tract
      inflammation (>10[4] polymorphonuclear leukocytes [PMNs]/ml). Use of this
      quantitative method will facilitate direct comparison of data obtained within and
      among laboratories and enable further research on factors affecting antibody
      levels in genital tract secretions and their effects on HIV-1 transmission.

PMID- 9257651
TI  - The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally
      homologous to the yeast splicing factors Prp4p and Prp3p.
AB  - Immunoaffinity-purified human 25S [U4/U6.U5] tri-snRNPs harbor a set of
      polypeptides, termed the tri-snRNP proteins, that are not present in Mono Q
      purified 20S U5 snRNPs or 10S U4/U6 snRNPs and that are important for tri-snRNP
      complex formation (Behrens SE, Luhrmann R, 1991, Genes & Dev 5:1439-1452).
      Biochemical and immunological characterization of HeLa [U4/U6.U5] tri-snRNPs led
      to the identification of two novel proteins with molecular weights of 61 and 63kD
      that are distinct from the previously described 15.5, 20, 27, 60, and 90kD tri
      snRNP proteins. For the initial characterization of tri-snRNP proteins that
      interact directly with U4/U6 snRNPs, immunoaffinity chromatography with an
      antibody directed against the 60kD protein was performed. We demonstrate that the
      60 and 90kD tri-snRNP proteins specifically associate with the U4/U6 snRNP at
      salt concentrations where the tri-snRNP complex has dissociated. The primary
      structures of the 60kD and 90kD proteins were determined by cloning and
      sequencing their respective cDNAs. The U4/U6-60kD protein possesses a C-terminal
      WD domain that contains seven WD repeats and thus belongs to the WD-protein
      family, whose best-characterized members include the Gbeta subunits of
      heterotrimeric G proteins. A database homology search revealed a significant
      degree of overall homology (57.8% similarity, 33.9% identity) between the human
      60kD protein and the Saccharomyces cerevisiae U4/U6 snRNP protein Prp4p. Two
      additional, previously undetected WD repeats (with seven in total) were also
      identified in Prp4p, consistent with the possibility that 60kD/Prp4p, like beta
      transducin, may adopt a propeller-like structure. The U4/U6-90kD protein was
      shown to exhibit significant homology, particularly in its C-terminal half, with
      the S. cerevisiae splicing factor Prp3p, which also associates with the yeast
      U4/U6 snRNP. Interestingly, U4/U6-90kD shares short regions of homology with E.
      coli RNase III, including a region encompassing its double-stranded RNA binding
      domain. Based on their structural similarity with essential splicing factors in
      yeast, the human U4/U6-60kD and 90kD proteins are likely also to play important
      roles in the mammalian splicing process.

PMID- 9257653
TI  - Absorption and elimination kinetics of zidovudine in the cerebrospinal fluid in
      HIV-1-infected patients.
AB  - Current knowledge of zidovudine (ZDV) levels in human cerebrospinal fluid (CSF)
      is limited to single sample determination and extrapolation to time after
      administration. Longitudinal studies have not been performed. Pharmacokinetic
      parameters of ZDV in CSF were determined in six HIV-1-infected patients. CSF
      samples were collected by an intraspinal catheter over a period of 6 hours after
      a single intravenous (IV) dose of ZDV (2.5 mg/kg). ZDV concentrations were
      measured by high-performance liquid chromatography (HPLC). ZDV was cleared
      rapidly from plasma, with a mean terminal elimination half-life (t 1/2) of 75.5
      +/- 4.9 minutes. ZDV penetrated slowly into the CSF, reaching maximal
      concentration (Cmax) 2 hours after the start of the infusion in all patients. ZDV
      was cleared from the CSF with a mean t 1/2 of 187.6 +/- 69.3 minutes. Mean Cmax
      in the CSF was 1.3 +/- 1.2 micromol/l (17% of that of plasma), and mean area
      under the concentration time curve (AUC) was 358 +/- 200 micromol x minutes/l
      (75% of that of plasma). There was a significant correlation between plasma and
      CSF for Cmax (r = 0.88, p = .009) and AUC (r = 0.89, p = .014). Calculated trough
      levels in CSF for a 12-hour dosing interval were 0.090 +/- 0.065 micromol/l and
      thus about twice the 50% inhibitory concentration (IC50) of susceptible HIV
      strains. The CSF-plasma ratio of ZDV increased in a nearly linear fashion with
      time after drug administration. Thus, ZDV has a distinct pharmacokinetic profile
      in CSF compared with other compartments of the body.

PMID- 9257654
TI  - Immune complex-dissociated p24 antigen in congenital or perinatal HIV infection:
      role in the diagnosis and assessment of risk of infection in infants.
AB  - Immune complex-dissociated (ICD) HIV-1 p24 antigen assay is a rapid technique for
      assessing the presence of HIV gag or core protein in plasma or serum. In this
      study, ICD p24 antigen detection in HIV-1 infected mothers and their infants
      enrolled in the Women and Infants Transmission Study (WITS) was evaluated
      primarily as a diagnostic assay for HIV-1 detection in young infants and for its
      association with perinatal transmission. Plasma from 47 infected infants and 160
      uninfected infants was examined, along with plasma from 197 of their mothers who
      had a delivery or close-to-delivery specimen. ICD p24 antigen was detected in
      plasma of 27.3% of infected infants at birth and in 70% to 81% at 1 to 6 months.
      The diagnostic specificity at birth was 90% and 98% to 100.0% at 1 to 6 months.
      The ICD p24 antigen concentration correlated with concurrent quantitative HIV
      culture results. The risk of transmission from mother to infant was higher if the
      mother had detectable ICD p24 antigen at or near the time of delivery (p =
      0.002), but its presence did not accurately predict transmission (positive
      predictive value of 36%, negative predictive values of 85%). The relative ease of
      performing the ICD p24 antigen assay and the low cost compared with that of HIV
      culture or DNA PCR makes this test a useful adjunct for the diagnosis of
      perinatal HIV infection and for enhancing understanding of its pathogenesis,
      particularly where cost and availability limit access to more sensitive assays.

PMID- 9257655
TI  - Elevated CD8+DR+ lymphocytes in HIV-exposed infants with early positive HIV
      cultures: a possible early marker of intrauterine transmission. Women and Infants
      Transmission Study Group.
AB  - The associations among timing of maternal-fetal human immunodeficiency virus
      (HIV) transmission, infant age at first positive HIV culture, and CD8+ lymphocyte
      activation were examined for 74 perinatally infected infants. Nineteen of the
      infected infants had positive HIV cultures at < or =7 days of life, and 55 had
      negative HIV cultures at < or =7 days but were positive later. Of the infants
      with early positive HIV-1 cultures, 15 of the 17 tested with DNA polymerase chain
      reaction methods had concordant results. The percentage of CD8+ and HLA-DR+
      lymphocytes (CD8+DR+%) during the first week of life was significantly higher in
      infants with early compared with late positive cultures (median CD8+DR+% of 5.0%
      versus 2.0%, p = 0.0006). The CD8+DR+% was similar between uninfected infants and
      infants with late positive cultures during the first week of life (median 2%) but
      increased in infants with late positive cultures to 6% by 1 month. The CD4+%
      during the first 6 months of life was not different between infants with early or
      with late positive cultures, but infants with the highest CD8+DR+% at < or =7
      days of life had significantly lower CD4+% at < or =7 days and at 1, 2, and 4
      months of age. These data show that early CD8+ lymphocyte activation is
      associated with early positive HIV cultures and lower CD4+ percentages during
      early infancy and are consistent with the hypothesis that early positive cultures
      positivity may indicate in utero HIV infection.

PMID- 9257656
TI  - Non-Hodgkin's lymphoma in HIV-positive and HIV-negative homosexual men in the San
      Francisco Bay Area: allergies, prior medication use, and sexual practices.
AB  - Lifestyle, sexual history, and medical history characteristics were analyzed as
      risk factors for non-Hodgkin's lymphoma (NHL) in a population-based case-control
      study of 1593 subjects with NHL and 2515 control subjects conducted in the San
      Francisco Bay Area between 1988 and 1995. The results for homosexual men, 312
      with NHL and 420 control subjects, showed that HIV infection was associated with
      a 20-fold increased risk for NHL. Among HIV-positive homosexual men, after
      adjustment for other factors, those that were associated with a reduced risk for
      NHL were frequency of receptive anal intercourse between the ages of 20 and 29 (1
      to 9 times: OR = 0.63; > or = 10 times: OR = 0.37; trend: p = 0.02), allergy to
      grass, hay, leaves, plants and pollen (OR = 0.35, CI = 0.19 to 0.64), number of
      bee or wasp stings (1 to 3 times: OR = 0.65; > or =4 times: OR = 0.56; trend: p =
      0.07), use of Tagamet (cimetidine) for 4 consecutive weeks or longer (OR = 0.39,
      CI = 0.17 to 0.89), vaccination against influenza (OR = 0.41, CI = 0.23 to 0.74),
      and lifetime frequency of amphetamine use (1 to 19 times: OR = 0.59; > or =20
      times: OR = 0.38; trend: p = 0.003). Among HIV-negative homosexual men, after
      adjustment for other factors, factors that were associated with NHL status were
      frequency of receptive anal intercourse between the ages of 20 and 29 (1 to 9
      times: OR = 0.39; > or =10 times: OR = 0.20; trend: p = 0.001), nonmedication
      allergies (OR = 0.43, CI = 0.21 to 0.89), vaccination against poliomyelitis at
      <10 years (OR = 0.41, CI = 0.17 to 0.99), and having five or more siblings (OR =
      3.6, CI = 1.7 to 7.7). An increased immunosuppressive effect of seminal fluid on
      sensitive rectal tissue and support from earlier work suggesting that HIV-related
      lymphomas may be outgrowths of antigen-driven B cells provide a possible
      mechanism for the results of this study. The role of allergic reactions in NHL is
      likely to be complex and may be related to B-cell differentiation. These
      associations may provide insight into an antigen-driven process early in
      lymphomagenesis.

PMID- 9257657
TI  - Non-Hodgkin's lymphoma in homosexual men in the San Francisco Bay Area:
      occupational, chemical, and environmental exposures.
AB  - Chemical, occupational, and other exposures as risk factors for non-Hodgkin's
      lymphoma (NHL) among homosexual men are reported from a population-based case
      control study of 1593 eligible subjects with NHL and 2515 control subjects
      conducted in the San Francisco Bay Area between 1988 and 1995. Results are
      presented for 312 homosexual men with NHL and 420 homosexual control subjects.
      HIV-positive patients were less likely than control subjects to have worked in
      technical, sales, and administrative occupations; service occupations; and
      precision production, craft, or repair-related occupations. They were likely to
      have had less exposure to petroleum products, aldehydes, cleaning solvents,
      adhesives, insecticides, welding fumes, and tar, pitch, soot, or ash. The HIV
      negative patients were less likely than the control subjects to have worked in
      managerial or professional specialty occupations and in technical, sales, or
      administrative occupations. HIV-negative patients were somewhat more likely than
      control subjects to have been exposed to herbicides (OR = 2.0, CI = 0.89 to 4.7),
      to radioactivity (OR = 4.7, CI = 1.7 to 13), and to tar, soot, pitch, or ash
      (250+ hours: OR = 2.3, CI = 0.96 to 5.6). HIV-negative NHL patients also were
      somewhat more likely to have lived on a farm as children than the control
      subjects (OR = 2.4, CI = 1.0 to 5.6). Pooled over HIV status, patients were
      somewhat more likely to have worked as motor vehicle or rail operators for more
      than 1 year (OR = 2.1, CI = 0.98 to 4.4). Most occupational exposures were of
      brief duration and many chemical exposures were reported as minimal. No clear and
      strong associations were found, although the risk for NHL related to exposure to
      several chemicals generally was reduced among HIV-positive men and elevated among
      HIV-negative men.

PMID- 9257658
TI  - Incidence of HIV and HTLV-1 infection among sexually transmitted disease clinic
      attenders in Jamaica.
AB  - Of 970 sexually transmitted disease (STD) patients enrolled at the Comprehensive
      Health Centre, Kingston, Jamaica, between November 1990 and January 1991, 710
      (73%, 333 men and 377 women) were reexamined between January 1992 and July 1993
      to estimate the incidence of HIV and HTLV-I infection and to identify risk
      factors for infection. Of those reexamined, 20% were recruited passively when
      they returned to the clinic of their own accord, and 80% were recruited actively
      through field visits to their homes. Passively recruited persons were
      significantly more likely than active recruits to have had a sexually transmitted
      disease since enrollment or at their follow-up visit. Seven men and one woman
      became HIV positive during the period of follow-up. The overall HIV incidence
      rate was 0.7 per 100 person years (95% confidence interval [CI] = 0.3 to 1.4),
      1.4 (CI = 0.6 to 2.8) for men and 0.2 (CI = 0.004 to 0.9) for women. Four of 270
      men and 4 of 318 women were HTLV-I positive, an overall incidence of 0.9 per 100
      person years (CI = 0.4 to 1.7), 1.0 for men and 0.8 for women. HTLV-I infection
      was associated with an age of 30 years or older (p < 0.01). The presumed lower
      transmission probability for HTLV-I may combine with a higher prevalence of HTLV
      I in sexual partners to produce similar overall incidence rates for the two
      infections. The HIV and HTLV-I incidence rates may have been underestimated,
      because the study subjects who did not return to the clinic may have had a
      somewhat higher risk. On univariate analysis, there were significant associations
      between HIV infection in men and drinking alcohol before sex, cocaine use, total
      number of sex partners, sex with a prostitute since enrollment, ever accepting
      money for sex, the average number of sex partners per month, bruising during sex,
      and genital ulcers found on follow-up examination. This analysis needs to be
      interpreted with caution in view of the small number of seroconverters, which did
      not allow testing for independent effects in a logistic regression model.

PMID- 9257659
TI  - HTLV-I and HTLV-II infections in hematologic disorder patients, cancer patients,
      and healthy individuals from Rio de Janeiro, Brazil.
AB  - To clarify the seroprevalence of human T-cell lymphotropic virus type I (HTLV-I)
      among hematologic and cancer patients in the State of Rio de Janeiro, Brazil, we
      investigated sera from 2430 individuals from the following groups: 152 patients
      with T-cell diseases, 250 with B-cell disorders, 67 with myeloid leukemia, 41
      with Hodgkin's disease, 351 with a history of multiple blood transfusions, 235
      patients with solid tumors of different types, and 109 family members of HTLV-I
      infected patients. Antibodies to HTLV-I were screened by enzyme-linked
      immunosorbent assay or particle agglutination assays (or both). Repeatedly
      reactive samples were tested by Western blot and polymerase chain reaction assay
      to differentiate HTLV-I from HTLV-II. We found an increased seroprevalence rate
      of HTLV-I among those with lymphoid malignancies, mainly in T-cell diseases
      (28.9%), and these results were important in characterizing 44 cases of adult T
      cell leukemia/lymphoma. We confirmed the presence of HTLV-I and HTLV-II
      infections in blood donors (0.4% and 0.1%, respectively), in patients exposed to
      multiple blood transfusions (10.2% and 0.8%, respectively), and in 30 (27.5%) of
      109 family members of HTLV-I- or HTLV-II-infected patients. We also confirmed the
      high rate occurrence of adult T-cell leukemia/lymphoma among lymphoproliferative
      disorders in Rio de Janeiro, Brazil.

PMID- 9257660
TI  - Influences of age, viral load, and CD4+ count on the rate of progression of HIV-1
      infection to AIDS. Transfusion Safety Study Group.

PMID- 9257661
TI  - A mechanistic analysis of nondisruptive axonal injury: a review.
AB  - Axons are particularly at risk in human diffuse head injury. Use of
      immunocytochemical labeling techniques has recently demonstrated that axonal
      injury (AI) and the ensuing reactive axonal change is, probably, more widespread
      and occurs over a longer posttraumatic time in the injured brain than had
      previously been appreciated. But the characterization of morphologic or reactive
      changes occurring after nondisruptive AI has largely been defined from animal
      models. The comparability of AI in animal models to human diffuse AI (DAI) is
      discussed and the conclusion drawn that, although animal models allow the
      analysis of morphologic changes, the spatial distribution within the brain and
      the time course of reactive axonal change differs to some extent both between
      species and with the mode of brain injury. Thus, the majority of animal models do
      not reproduce exactly the extent and time course of AI that occurs in human DAI.
      Nonetheless, these studies provide good insight into reactive axonal change. In
      addition, there is developing in the literature considerable variance in the
      terminology applied to injured axons or nerve fibers. We explain our current
      understanding of a number of terms now present in the literature and suggest the
      adoption of a common terminology. Recent work has provided a consensus that
      reactive axonal change is linked to pertubation of the axolemma resulting in
      disruption of ionic homeostatic mechanisms within injured nerve fibers. But
      quantitative data for changes for different ion species is lacking and is
      required before a better definition of this homeostatic disruption may be
      provided. Recent studies of responses by the axonal cytoskeleton after
      nondisruptive AI have demonstrated loss of axonal microtubules over a period up
      to 24 h after injury. The biochemical mechanisms resulting in loss of
      microtubules are, hypothetically, mediated both by posttraumatic influx of
      calcium and activation of calmodulin. This loss results in focal accumulation of
      membranous organelles in parts of the length of damaged axons where the axonal
      diameter is greater than normal to form axonal swellings. We distinguish, on
      morphologic grounds, between axonal swellings and axonal bulbs. There is also a
      growing consensus regarding responses by neurofilaments after nondisruptive AI.
      Initially, and rapidly after injury, there is reduced spacing or compaction of
      neurofilaments. This compaction is stable over at least 6 h and results from the
      loss or collapse of neurofilament sidearms but retention of the filamentous form
      of the neurofilaments. We posit that sidearm loss may be mediated either through
      proteolysis of sidearms via activation of microM calpain or sidearm
      dephosphorylation via posttraumatic, altered interaction between protein
      phosphatases and kinase(s), or a combination of these two, after calcium influx,
      which occurs, at least in part, as a result of changes in the structure and
      functional state of the axolemma. Evidence for proteolysis of neurofilaments has
      been obtained recently in the optic nerve stretch injury model and is correlated
      with disruption of the axolemma. But the earliest posttraumatic interval at which
      this was obtained was 4 h. Clearly, therefore, no evidence has been obtained to
      support the hypothesis that there is rapid, posttraumatic proteolysis of the
      whole axonal cytoskeleton mediated by calpains. Rather, we hypothesize that such
      proteolysis occurs only when intra-axonal calcium levels allow activation of mM
      calpain and suggest that such proteolysis, resulting in the loss of the
      filamentous structure of neurofilaments occurs either when the amount of
      deformation of the axolemma is so great at the time of injury to result in
      primary axotomy or, more commonly, is a terminal degenerative change that results
      in secondary axotomy or disconnection some hours after injury.

PMID- 9257662
TI  - High-resolution 1H NMR spectroscopy following experimental brain trauma.
AB  - We investigated acute metabolic changes following parasagittal fluid-percussion
      brain injury in the rat, using high-resolution 1H nuclear magnetic resonance
      (NMR) spectroscopy. Sixty minutes following brain injury or sham (surgery, no
      injury) treatment, brains were rapidly removed and the injured and control
      cortices were isolated (n = 5/group). Isolates of brain cortices were then placed
      in buffer and studied in a 400-MHz spectrometer with measurements taken every 15
      min over a 145-min period. At the initial NMR evaluation (immediately following
      dissection), we observed significantly lower levels of N-acetyl aspartic acid
      (NAA) in the injured group compared to the sham group. Surprisingly, a reciprocal
      increase in the concentration of acetate, a major metabolic product of NAA, was
      not observed at this timepoint. At subsequent timepoints, a progressive loss of
      NAA was observed in both injured and sham cortices, presumably due to ischemic
      conditions of the ex vivo samples. However, this progressive loss of NAA was now
      accompanied by a commensurate accumulation of acetate. These results suggest that
      (1) a decrease in the concentration of NAA occurs by 1 h following experimental
      brain trauma, potentially marking traumatic neural injury; (2) the initial
      absence of an expected reciprocal increase in acetate concentration may signify
      rapid utilization of acetate following trauma, potentially for reparative
      processes; and (3) in contrast to trauma alone, post mortem ischemic conditions
      may induce an increase in acetate concentrations.

PMID- 9257663
TI  - Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic
      brain injury in children.
AB  - Cytokines may play an important role in the pathophysiology of traumatic brain
      injury (TBI) in children. Interleukin-6 (IL-6) is a proinflammatory cyotkine that
      plays a role in regenerative processes within the central nervous system (CNS),
      whereas interleukin-10 (IL-10) is an antiinflammatory cytokine. Both have been
      measured in serum and cerebrospinal fluid (CSF) as an index of the degree of
      inflammation in diseases, including sepsis and meningitis. We hypothesized that
      both IL-6 and IL-10 would be increased in the CSF of children after severe TBI.
      Fifteen children who sustained severe TBI (Glascow Coma Score [GCS] < or = 7)
      were studied. Standard neurointensive care was provided. Ventricular CSF
      collected the first 3 days after TBI was analyzed for IL-6 and IL-10
      concentrations by ELISA. Controls were 20 children who were evaluated for
      meningitis with diagnostic lumbar puncture subsequently found to have no CSF
      pleocytosis and negative cultures. IL-6 was increased in children after TBI
      versus controls on all days studied (day 1, 3158.2 +/- 621.8 pg/ml; day 2, 1111.6
      +/- 337.0 pg/ml; day 3, 826.7 +/- 193.5 pg/ml vs. 20.6 +/- 5.8 pg/ml, p < 0.0001,
      Mann-Whitney Rank Sum). IL-10 was increased in children after TBI vs controls on
      all days studied (day 1, 47.2 +/- 12.9 pg/ml; day 2, 21.0 +/- 6.7 pg/ml; day 3,
      15.5 +/- 5.9 pg/ml vs. 8.9 +/- 7.5 pg/ml, p < 0.01). Increased IL-10
      concentrations were independently associated with age < 4 years and mortality (p
      = 0.004 and 0.04, respectively, multivariate linear model). This study
      demonstrates that IL-6 is increased after TBI in children to levels similar to
      those reported in adults and is the first to show that IL-10 is increased in CSF
      of humans after TBI. These data suggest that there may be an age-dependent
      production of IL-10 after TBI in children.

PMID- 9257664
TI  - Amphetamine and task-specific practice augment recovery of vibrissae-evoked
      forelimb placing after unilateral sensorimotor cortical injury in the rat.
AB  - This study investigated the relative contribution of amphetamine administration
      and task-specific practice during the period of drug action to recovery of
      forelimb-placing ability after unilateral electrolytic lesions of the
      sensorimotor cortex (SMC) in rats. Subjects were divided into groups receiving
      amphetamine plus postinjection forelimb-placing practice, amphetamine only,
      saline plus postinjection forelimb-placing practice, or saline only. The results
      revealed that groups of subjects receiving either amphetamine, postinjection
      practice, or a combination of these treatments exhibited the greatest enhancement
      of rates of vibrissae-evoked forelimb-placing recovery. These data suggest that
      these treatments can have an enduring beneficial effect on vibrissae-evoked
      forelimb-placing recovery without any immediate restorative effect on forelimb
      placing ability. The recovery patterns and experimental evidence (see Feeney and
      Sutton, 1988; Chaouloff, 1989) suggest that the beneficial effect of the two
      therapies may be mediated by catecholamine release.

PMID- 9257666
TI  - Endovascular surgery: back to basics.

PMID- 9257665
TI  - Pretreatment with alpha-phenyl-N-tert-butyl-nitrone (PBN) improves energy
      metabolism after spinal cord injury in rats.
AB  - We evaluated in rats, the effect of the spin trap alpha-phenyl-N-tert-butyl
      nitrone (PBN) on energy metabolism after severe spinal cord injury (SCI). A
      laminectomy of vertebrae Th7 and Th8 was made. A probe was inserted in a dorsal
      horn, and microdialysis was performed for 1.5 h before and 4 h after applying
      severe compression (4.5 g/mm2) for 5 min. Thirty minutes before trauma 30-mg/kg
      PBN or saline was given intravenously and a second dose of 10 mg/kg after 3 h.
      Microdialysis samples were collected at intervals of 10 min and analysed by high
      performance liquid chromatography. As reported previously there was a severalfold
      rise of lactate after trauma. The mean level of lactate was consistently lower in
      animals pretreated with PBN, but the difference was statistically significant
      between the groups only at 200 min after trauma. Lactate normalized more rapidly
      in PBN pretreated animals. In saline-treated rats, hypoxanthine quickly rose and
      reached a maximum 23 times above basal level 20 min after trauma, while the rise
      was 14 times in PBN pretreated rats. The increase of hypoxanthine was
      significantly lower and normalized more rapidly in PBN pretreated animals. This
      study suggests that PBN pretreatment attenuates lactic acidosis and improves
      energy metabolism after severe SCI. The effect may, at least partly, reflect
      amelioration of radical induced mitochondrial dysfunction.

PMID- 9257667
TI  - Iliac transluminal angioplasty and distal surgical revascularisation can be
      performed in a one-step technique.
AB  - PURPOSE: A few authors have suggested treating double-level atherosclerotic
      lesions in high risk patients by an association of iliac transluminal angioplasty
      (ITA) and distal surgical restoration in a two-step technique with an interval of
      one to three weeks between the two procedures. Previous reports of ITA showed the
      influence of the quality of the outflow on early results, we therefore decided to
      perform the two procedures mentioned above during the same operation. METHODS:
      During a five-year period, 51 patients (42 men, 9 women) underwent an isolated
      ITA in 32 cases (group I) or associated with a simultaneous surgical
      reconstruction (group II) in 19 cases. Mean age (56.4+/-12 years versus 63.9+/
      11.8 years, p<0.01), frequency of limb-threatened ischaemia (2.6% versus 42.1%
      p<0.001), and of an ipsilateral thrombosed or severely stenotic femoral artery
      (20% versus 100%, p<0.001) were significantly higher in group II. In group I
      (n=32), 45 unique or double iliac lesions (unilateral=25, bilateral=7) including
      42 stenosis (>75%) and three thrombosis were treated. In group II (n=19), ITA was
      performed on unique and unilateral iliac stenosis (>75%) in association with a
      femoro-femoral bypass (n=4), an ipsilateral femoro-popliteal bypass (n=5) or
      femoro-tibial bypass (n=3) or an ipsilateral deep or common femoral
      reconstruction (n=7). RESULTS: Early complications consisted of one haematoma
      (group I), one death and one iliac restenosis (group 2). After a mean follow-up
      of 20 months, cumulative patency of groups I and II was respectively 81% and 88%
      (p=ns), with an increase in the ankle/brachial systolic pressure ratio from
      0.73+/-0.14 to 0.92+/-0.14 (p<0.001) in group I, and from 0.57+/-0.15 to 0.84+/
      0.12 (p<0.001) in group II. CONCLUSIONS: Early and mid-term results of the one
      step technique are similar to those obtained with patients who underwent ITA with
      good initial outflow. This technique can therefore be recommended in high-risk
      patients with double-level atherosclerotic lesions including severe iliac
      stenosis.

PMID- 9257668
TI  - Anticardiolipin antibodies are not associated with restenosis or endothelial
      activation after percutaneous transluminal angioplasty.
AB  - OBJECTIVE: Restenosis following percutaneous transluminal angioplasty (PTA)
      continues to be a major clinical problem. Anticardiolipin antibodies (aCL) have
      been established as risk factors for venous or arterial thrombosis. The aim of
      this study was to assess: a) the influence of positive aCL upon restenosis within
      6 months after PTA, b) the possibility of a seroconversion from negative to
      positive aCL after PTA and c) a possible link between positive aCL and
      endothelial activation. EXPERIMENTAL DESIGN: 71 patients (50 men and 21 women,
      age 68+/-13 years) with peripheral arterial occlusive disease (PAOD, Fontaine II
      IV) undergoing a successful PTA entered the study and were prospectively followed
      for 3 and 6 months thereafter. INTERVENTIONS: PTA was carried out successfully
      and noninvasive grading was done with duplex scanning. Laboratory investigation
      included aCL, thrombin generation markers, such as thrombin-antithrombin III
      complexes and prothrombin fragments 1+2, as well as thrombomodulin, soluble P
      selectin, E-selectin and the vascular cell adhesion molecule-1, as endothelial
      activation markers. RESULTS: 30/71 (42.3%) patients developed restenosis (>50%
      reduction of the lumen diameter) within 6 months after PTA. 9/71(12.7%), had
      positive aCL IgG (19-35 GPL) and/or IgM (14-103 MPL) at all three measurements.
      2/9 (22.2%) of aCL positive and 28/62 (45.2%) of aCL negative patients had
      restenosis at 6 months after PTA (relative risk RR=0.51, 95%-Cl: 0.14-1.78, chi2
      non-significant). All other parameters did not differ between aCL positive and 
      negative groups. CONCLUSIONS: Our findings suggest that: a) patients with PAOD
      have a slightly higher prevalence of positive aCL compared to the general
      population, but no association is evident between positive aCL and restenosis
      within 6 months after PTA, b) no seroconversion from negative to positive aCL
      occurred within 6 months after PTA, c) no association of aCL with endothelial
      activation markers or thrombin generation markers was found.

PMID- 9257669
TI  - Optimal dose and duration of heparin for inhibition of intimal hyperplasia.
AB  - BACKGROUND: A Dacron patch graft was placed in the common carotid artery of sheep
      to assess the effect of three different doses of unfractionated heparin
      administered for periods of one to four weeks. MATERIALS AND METHODS: Animals
      were divided into a control group (n=6) in which animals received a patch graft
      but no heparin and three main treatment groups on the basis of the dose of
      heparin received. Group 1 animals (n=24) received 140 units per kg daily in two
      divided doses. Group 2 (n=24) received 280 units per kg daily and Group 3 (n=24)
      received 420 units per kg daily. Each treatment group was further divided into
      four subgroups on the basis of the duration of treatment. Groups 1(i), 2(i), 3(i)
      had treatment for one week. Groups 1(ii), 2(ii), 3(ii) had treatment for two
      weeks. Groups 1(iii), 2(iii), 3(iii) had treatment for three weeks. Groups 1(iv),
      2(iv), 3(iv) had treatment for four weeks. There were six animals in each
      subgroup giving a total of 72 treated sheep. Animals were sacrificed at four
      weeks and an intimal measurement in pm was obtained under light microscopy from a
      transverse sectioned segment of artery containing the patch graft using an
      eyepiece graticule. RESULTS: There were no haemorrhagic complications. Control
      animals had a mean intimal thickness of 176 pm. All treatment groups had
      significantly less IH--Group 1 131.9 (p<0.01), Group 2 138.5 (p<0.05), Group 3
      117.8 (p<0.01). There were no significant differences between the treatment
      groups. There was significantly less IH in animals treated for four weeks (106.3)
      compared to one week (140.2, p<0.05). CONCLUSIONS: This study indicates that
      inhibition of IH can be achieved by heparin with optimal effect from a four week
      treatment period.

PMID- 9257671
TI  - The role of profunda femoris revascularization in aortofemoral surgery. An
      analysis of factors affecting graft patency.
AB  - BACKGROUND: To determine the long-term results of aortofemoral grafts using the
      profunda femoris artery as an outflow vessel and to determine the factors
      affecting the outcome of these procedures. DESIGN: Prospective study. METHODS:
      From 1980 to 1993, 224 profundoplasties were performed as an adjunctive outflow
      procedure of aortofemoral grafts in 180 patients. There were 167 men and 13 women
      with a mean age of 63.7 years. Severe claudication was the indication for
      operation in 147 limbs (65.6%), and critical ischemia in 77 (34.4%). Good runoff
      was present in 159 limbs (71%), while poor run-off in 65 (29%). Profundoplasty
      was extended distally in 67 cases (29.9%), while in the remaining 157 (70.1%) it
      was limited to the proximal portion of the artery. Arterial and venous patches
      were used alternatively for the profundoplasty. RESULTS: The 30-day mortality was
      1.6% and the 5-year and 9-year survival rate was 69.7% and 49.1% respectively.
      Primary graft patency was 87.2% in 5 years and 78.5% in 9 years, while secondary
      graft patency was 90.1% in 5 years and 81.4% in 9 years. Limb salvage rate was
      92.7% in 5 years and 87.6% in 9 years. There were four factors which were
      predictive of inferior longterm results namely; critical ischemia, poor run-off,
      extended profundoplasty and vein patch used for the profundoplasty. CONCLUSIONS:
      Angioplasty of the profunda femoris artery is a durable outflow procedure for
      aortofemoral graft surgery, when the above mentioned risk factors are absent;
      however when they do exist, the use of arterial patch for profundoplasty may
      improve the prognosis.

PMID- 9257670
TI  - The effects of platelet inhibitors on platelet uptake and restenosis after
      femoral angioplasty.
AB  - OBJECTIVE: To investigate the effects of two platelet inhibitors, aspirin and
      iloprost, on platelet uptake and restenosis at the site of angioplasty in
      patients undergoing femoral or popliteal angioplasty. EXPERIMENTAL DESIGN:
      Prospective, open, randomised group comparison. SETTING: Two university
      hospitals. PATIENTS: 43 patients undergoing femoral or popliteal angioplasty were
      randomised. INTERVENTIONS: Patients received either aspirin (300 mg/day),
      iloprost (8 hours/day i.v. infusion) or no antiplatelet medication during
      angioplasty and on the subsequent two days. MEASURES: Platelet uptake was
      measured using 111Indium-labelled platelets. Restenosis was assessed by repeat
      angiography at 3 months and clinical symptoms up to 12 months. RESULTS: Median
      changes in platelet uptake were similar in the three treatment groups, but all
      platelet radioactivity ratios > 2.0 occurred in the control group. Restenosis at
      3 months was observed in 3 control, 5 aspirin and 1 iloprost patient. Further
      surgical intervention was performed in 3 control and 3 aspirin patients, but in
      none of the iloprost patients up to 12 months after angioplasty. CONCLUSIONS:
      Antiplatelet therapy may prevent large increases in platelet deposition at the
      angioplasty site, but the link between platelet deposition and restenosis was not
      substantiated in this study.

PMID- 9257672
TI  - Screening for concomitant diseases in peripheral vascular patients. Results of a
      systematic approach.
AB  - BACKGROUND: Patients considered for arterial surgery, have been shown to have a
      high incidence of coexistent cardiac, vascular and other diseases, affecting
      operative risk and survival. We developed a systematic workup strategy for
      detecting these coexistent diseases in our vascular surgical patients, mainly
      based on non-invasive diagnostic techniques. METHODS: We evaluated 200
      consecutive patients, admitted to the department of vascular surgery in an
      academic teaching hospital, in order to establish the total incidence of relevant
      concomitant disorders, the extent to which this screening yielded previously
      unknown diagnostic information, and the impact on short-term (one year) survival.
      RESULTS: Coronary artery disease was present in 46% of the patients; 22% had
      active ischaemia, newly diagnosed in 5.5%. Impaired cardiac function was found in
      37%: severely impaired in 12%, newly diagnosed in 27%. Carotid artery disease was
      present in 32%: critical stenoses were found in 9%; new diagnoses in 29.9%.
      Aortic aneurysms were present in 7%, newly diagnosed in 5%. Severe renal artery
      stenosis was present in 5%, newly diagnosed in 3.5%. Sixteen % of the patients
      had chronic obstructive pulmonary disease, newly diagnosed in 3.5%, and 4.5% had
      unexpected disorders, which were all new diagnoses. Overall, new diagnoses were
      reached in 64.5% of the population, affecting therapeutic strategy immediately in
      21% of the patients. The presence of coronary artery disease and of cardiac
      failure were clearly related to one year survival. CONCLUSIONS: We conclude that
      a systematic screening strategy, mainly based on noninvasive techniques, can
      detect the presence of concomitant diseases in the vascular surgical patient.
      Most important seem the newly diagnosed diseases altering surgical management in
      one out of every five patients; they also have important implications for patient
      prognosis.

PMID- 9257673
TI  - The distribution of peripheral arterial disease in a defined population of
      elderly high-risk Saudi patients.
AB  - OBJECTIVES: To find out the prevalence rate of peripheral arterial disease (PAD)
      in a defined population of high risk Saudi patients aged 50-80 years, using
      simple measuring techniques. DESIGN: A hospital-based cross-sectional study using
      a simple protocol. MATERIALS AND METHODS: Four groups of patients were studied:
      three high risk groups (214 cases of diabetes (DS), 60 of chronic renal failure
      (CRF), 78 of ischaemic heart disease (IHD) and 50 controls. PAD was only
      diagnosed if the ankle-brachial index (ABI) was < or =0.9. The contribution of a
      history of intermittent claudication (IC) and palpation of pulses to the
      diagnosis was assessed. RESULTS: A total of 402 patients was studied. Their mean
      age was 59.31+/-8.1 (range 50-80). There were 257 males (63.9%) and 145 females
      (36.1%). 171 cases of PAD were detected (42.5%) and distributed among the various
      groups: 105 (61.4%) in the DM, 23 (13.4%) in the CRF, 36 (21.4%) in the IHD and 7
      (4.1%) in the control groups. The prevalence rate was highly significant in each
      of the 3 high risk groups compared to the control group; however, there was no
      statistically significant difference in the incidence of PAD between the high
      risk groups. Questionnaires for IC and palpation of peripheral pulses were of
      very limited validity in diagnosing PAD. Overall, DM headed the list of
      significant risk factors followed by smoking and greater age. CONCLUSIONS: In
      contrast to the general impression that PAD is an uncommon disease, we found a
      significant prevalence rate of PAD in elderly high risk patients. Screening for
      PAD in aged diabetics, IHD and CRF patients is a simple and cost-effective
      approach.

PMID- 9257674
TI  - Behaviour of arm venous pressure in patients with systodiastolic hypertension and
      in the elderly with isolated systolic hypertension in comparison with healthy
      controls.
AB  - The aim of our study was to evaluate the behaviour of venous pressure in patients
      with systodiastolic arterial hypertension as compared with elderly patients
      suffering from isolated systolic hypertension and with healthy controls. We
      studied 125 subjects subdivided into three groups: Group A, formed by 32
      patients, aged between 43 and 73 years, with a mean age of 63.25+/-12.3 years,
      suffering from mild to moderate systodiastolic essential arterial hypertension
      (SDH); Group B, including 50 patients, aged between 58 and 83 years, with a mean
      age of 71.53+/-8.43 years, with isolated systolic hypertension (ISH); Group C,
      formed by 43 subjects, aged between 13 and 72 years, with a mean age of 42.91+/
      17.84 years, as a healthy control group (CS). Patients observed a period of
      pharmacological washout for at least 15 days before the beginning of the study.
      All underwent a diet with a normal sodium intake. Brachial arterial pressure was
      always measured at 9 a.m., by using a mercury sphygmomanometer. The venous
      pressure was measured at the fold of the elbow on the basilic vein, using a
      Doppler ultrasound instrument. The SBP was similar in patients with SDH (Group A)
      and in those with ISH (Group B); in both groups SBP was significantly higher than
      in CS (Group C) (p<0.001). The DBP was significantly higher especially in
      patients of group A, but also in patients of group B, in comparison with subjects
      of group C and in patients with SDH in comparison with those with ISH. Venous
      pressure (VP) proved to be significantly higher in both groups of hypertensives
      in comparison with CS and in SDH in comparison with ISH (14.76+/-1.90 in Group A
      vs 12.53+/-2.39 in group B vs 8.75+/-2.02 mmHg in group C, p<0.0001). Considering
      ten subjects, matched for sex and age in each group, we observed again that VP
      values in SDH were >ISH>CS (14.3+/-2.9 vs 9.7-/+1.8 in SDH vs CS, 13.5-/+2.1 vs
      10.7+/-1.9 in ISH vs CS, 15.6+/-2.2 vs 11.6+/-2.6 mm Hg in SDH vs ISH, p<0.001).
      In all three considered groups a significant correlation between the values of
      SBP and DBP with VP (p<0.001) was observed. In conclusion, data from our study
      show that hypertension is a disease in which both the arterial and the venous
      vascular beds are involved with increased pressure in both circulatory beds.

PMID- 9257675
TI  - Perfused human saphenous veins for the study of the origin of varicose veins:
      role of the endothelium and of hypoxia.
AB  - If venous stasis due to blood stagnation has been recognized to be involved in
      the development of varicose veins, the mechanism linking this situation to the
      modifications of the venous wall observed in varicoses is still unclear. In order
      to study this mechanism, human saphenous veins were incubated in normoxic or
      hypoxic conditions and the interactions between the endothelium and neutrophils
      were investigated. We observed that many neutrophils adhered to the endothelium
      of veins incubated in hypoxic conditions rather than in normoxia and that these
      adherent neutrophils were activated: they released high amounts of superoxide
      anion and of leukotriene B4. Studies in scanning electron microscopy confirmed
      the increased neutrophil adherence to the endothelium as well as their
      activation. These results were then related to the histological observation of
      varicose veins. These veins show a thickening of the media with extracellular
      matrix deposit as well as an alteration of the elastic lamina with the presence
      of smooth muscle cells in the intima. These results are in agreement with in
      vitro studies on isolated endothelial cells. They all show that hypoxia is able
      to activate endothelial cells: they release inflammatory mediators and become
      adhesive for neutrophils which are then activated. These activated leukocytes
      release free radicals and proteases which are able to degrade the extracellular
      matrix. In addition, hypoxia-activated endothelial cells secrete growth factors
      which will trigger smooth muscle cell proliferation and the synthesis of
      extracellular matrix components. Altogether and because they are frequently
      repeated, these processes could eventually lead to alterations of the venous wall
      similar to those observed in varicose veins.

PMID- 9257676
TI  - The value of duplex ultrasound in the follow-up of acute calf vein thrombosis.
AB  - Calf veins are one of the most common sites for deep vein thrombosis (DVT) but
      the management of patients with calf vein thrombosis differs. Many centres
      consider pharmacological treatment unnecessary and elect not to examine the calf
      veins with duplex ultrasound. Others advocate monitoring the thrombus with serial
      venous duplex scanning and commence treatment if there is evidence of
      propagation. In this laboratory duplex scanning of the calf veins is routinely
      carried out as part of the diagnostic procedure for DVT. A study was carried out
      where 50 patients with isolated calf vein thrombosis were followed over a one
      year period to determine the long term outcome in the calf veins. Note was made
      of the choice of treatment. A high percentage (85%) were treated with
      heparin/warfarin and only 15% received no pharmacological treatment. There was a
      propagation rate of 15%, one of which resulted in a fatal pulmonary embolus (PE).
      The DVT recurrence rate was 14% within the year. No long term effects such as
      valvular damage were noted during the follow-up period. The results suggest the
      need for better guidelines for the diagnosis and treatment of isolated calf vein
      thrombosis. Future studies with larger groups of patients need to be carried out
      to determine the significance of the recurrence rate and the long term effects.
      Duplex scanning enhances the diagnosis of calf vein thrombosis and should be used
      for closer observation of potential thrombus propagation.

PMID- 9257677
TI  - Pseudo-occlusion of the internal carotid artery: report of 15 cases and review of
      the literature.
AB  - Pseudo-occlusion of the internal carotid artery represents a difficult diagnostic
      problem. Meticulous investigation is mandatory whenever there is any suspicion of
      pseudo-occlusion, since it can easily be removed with endoarterectomy. Fifteen
      patients were selected in the last twelve years from those participating in a
      prospective study on the natural history of total occlusion of the internal
      carotid artery. The mean follow-up was 4.2 years (ranging from 1 to 12). Pseudo
      occlusion was diagnosed by duplex examination in the presence of a continuous
      signal with filling in of the spectral waveform window and no pulsatile flow.
      Arteriography showed a segmental occlusion of the internal carotid artery with
      reconstitution of flow in the distal portion of the vessel. Operations were
      performed under general anesthesia with EEG monitoring. Intraluminal shunt was
      necessary in only one patient. Patch closure of the arteriotomy was performed in
      two patients. All patients were put on Ticlopidin "sine die" after the operation.
      No mortality or strokes occurred in the perioperative period. Two patients
      presented with ipsilateral TIA after 7 months and one year, respectively. We
      conclude that: the incidence of this disease is low; the performance of duplex
      scan in combination with arteriography is essential in order to obtain the
      diagnosis of pseudo-occlusion; a strong suspicion of carotid pseudo-occlusion
      should always spring to mind when an apparently occluded carotid artery continues
      to be symptomatic or when, in asymptomatic patients, there is some discordance
      between angiography and Doppler or duplex scan findings; pseudo-occlusion should
      be considered an indication for urgent operation only in selected symptomatic
      patients.

PMID- 9257678
TI  - Relevance of Na,K-ATPase to local extracellular potassium homeostasis and
      modulation of synaptic transmission.
AB  - The ion gradients generated by the Na,K-ATPase are essential for Na+-coupled
      transport systems, osmoregulation and restoration of ion concentrations in
      excitable tissues. Indirectly, the sodium pump controls intracellular Ca2+
      concentration through the Na/Ca exchanger. In the nervous system various
      neurotransmitters can modulate Na,K-ATPase activity. The great diversity of Na,K
      ATPase subunit isoforms, their complex spatial and temporal regulation of
      expression and their cellular localisation imply a functional role of the sodium
      pump in different regulatory pathways. Among these, potassium homeostasis and
      modulation of synaptic transmission are discussed here.

PMID- 9257679
TI  - Conservative Val47 residue of POU homeodomain: role in DNA recognition.
AB  - Conservative Val47 residue, located in the third recognition helix of the Oct-2
      POU domain, was alternately substituted with other 19 amino acids. Affinity and
      specificity of interaction with oct-site ATGCAAANGA and homeo-specific site
      ATAANGA were determined for all mutants. The wild type protein (with Val47) has
      maximal affinity and specificity in POU domain interaction with octamer sequence.
      However, V47I mutant showed stronger interaction with homeo-specific site. The
      highest specificity of interaction with homeo-site was recorded for V47S mutant.
      We conclude that only Val47 provides sequence-specific high-affinity binding of
      POU proteins with octamer targets other than the homeo-specific site. It is shown
      also that damages caused by point mutations may be at least partially compensated
      by participation in the oct-site recognition of both POUh and POUs domains.

PMID- 9257680
TI  - Positive and negative regulation of JNK1 by protein kinase C and p42(MAP kinase)
      in adult rat hepatocytes.
AB  - The role of protein kinase C (PKC) and p42(MAP kinase) signaling in the
      regulation of proliferation and apoptosis was investigated in freshly isolated
      and primary cultured rat hepatocytes. Acute treatment of freshly isolated
      hepatocytes with phenylephrine and EGF caused rapid phasic activations of p42(MAP
      kinase) and JNK1. Acute pre-treatment of hepatocytes with the PKC inhibitors
      sphingosine, chelerythrine and bis-indolylmaleimide abolished the ability of
      phenylephrine, but not EGF, to activate p42(MAP kinase) and JNK1. Acute
      pretreatments with all of the PKC inhibitors alone increased JNK1 basal activity
      approximately 2-fold. Acute treatments of primary cultures of hepatocytes with an
      inhibitor of MEK1 activation (PD98059) also caused inhibition of p42(MAP kinase)
      and a approximately 2-fold activation of JNK1. These data demonstrate that PKC
      can function as both a proximal activator and a distal inhibitor of signaling
      through the JNK1/SAP kinase pathway. Treatments (4 h) of primary cultured
      hepatocytes with sphingosine, chelerythrine, bis-indolylmaleimide and PD98059 did
      not induce apoptosis as judged by propidium iodide staining. Similar acute
      treatments of HepG2 cells rapidly induced cell death. These data demonstrate that
      acute inhibition of either PKC or p42(MAP kinase) function is sufficient to
      rapidly induce apoptosis in transformed, but not in non-transformed hepatocytes.

PMID- 9257681
TI  - The conformational preference of gramicidin channels is a function of lipid
      bilayer thickness.
AB  - In order to understand how the material properties of lipid bilayers could affect
      integral membrane protein function, we examined the effect of a hydrophobic
      mismatch on the structure and function of membrane-spanning gramicidin channels.
      Changes in lipid bilayer thickness affect the conformational preference of
      membrane-spanning gramicidin A (gA) channels (single-stranded [SS] dimers <-->
      double-stranded [DS] dimers) and induces an additional conductance state in the
      standard (SS) beta6.3-helical channel. These results provide experimental
      evidence for the importance of energetic coupling between the bilayer and
      imbedded inclusions.

PMID- 9257682
TI  - Inherited retinal degeneration: basic FGF induces phagocytic competence in
      cultured RPE cells from RCS rats.
AB  - In RCS rats, the retinal pigment epithelium (RPE) is defective in phagocytosis of
      photoreceptor membranes. We have previously shown reduced expression of basic
      fibroblast growth factor (bFGF) in the RPE of 7-10-day-old RCS rats. This study
      using primary RPE cultures from rats of this age demonstrates that the phagocytic
      defect in the mutant RPE can be overcome by treatment with bFGF, by a mechanism
      involving gene transcription and that normal RPE phagocytosis, also requiring
      transcription, is blocked by a bFGF neutralizing antibody. The combined data
      point to a role for bFGF in the normal mechanism of RPE phagocytosis and the RCS
      defect.

PMID- 9257683
TI  - TPA induces translocation but not down-regulation of new PKC isoform eta in
      macrophages, MDCK cells and astrocytes.
AB  - New type protein kinase C (PKC) eta was found to be expressed in RAW 264.7 and
      J774A.1 macrophages, Madin-Darby canine kidney (MDCK) cells and astrocytes by
      Western blot analysis. Both cytosol and membrane in macrophages and astrocytes
      express this isoform, however, the expression in the membrane is more abundant
      than that in the cytosol. On the other hand, only membrane PKC eta was detected
      in MDCK cells. Exposure of the cells to 1 microM TPA for 10 min resulted in the
      translocation of PKC eta from the cytosolic to the membrane fraction. This
      translocation maintained at a constant level after 1.5, 3, 6 and 24 h TPA
      treatment. However, another new type PKC delta which expressed in the macrophages
      and astrocytes was down-regulated after long-term (6 and 24 h) TPA treatment. The
      immunoreactive band of PKC eta in J774A.1 macrophages was blocked by the control
      PKC eta antigenic peptide. Incubation of RAW 264.7 macrophages with UTP (1, 10
      and 100 microM) resulted in the accumulation of inositol phosphates, indicating
      the presence of P2 receptor-coupled PLC pathway in these cells. This natural
      activator UTP also induced translocation of PKC eta from cytosol to the membrane
      in RAW 264.7 macrophages after 1, 5 or 10 min treatment. Immunofluorescence
      microscopy revealed that in RAW 264.7 cells, PKC eta is located in the cytoplasm
      organelle, plasma membrane and nuclear envelope. Stimulation of the cells with
      TPA resulted in translocation to the plasma membrane. This translocation of PKC
      eta was still apparent after 24 h treatment with TPA.

PMID- 9257684
TI  - 3-Methoxynaltrexone, a selective heroin/morphine-6beta-glucuronide antagonist.
AB  - Recent work has suggested that heroin and morphine-6beta-glucuronide (M6G) both
      act through a novel mu opioid receptor subtype distinct from those mediating
      morphine's actions. This very high affinity 3H-M6G site is selectively competed
      by 3-methoxynaltrexone. In vivo, 3-methoxynaltrexone (2.5 ng, i.c.v.) selectively
      antagonizes the analgesic actions of heroin and M6G without interfering with mu
      (morphine and [D-Ala2,MePhe4,Gly(ol)5]enkephalin), delta ([D-Pen2,D
      Pen5]enkephalin), kappa1 (U50,488H) or kappa3 (naloxone benzoylhydrazone)
      analgesia. In dose-response studies, 3-methoxynaltrexone (2.5 ng, i.c.v.)
      significantly shifted the ED50 values for heroin and its active metabolite, 6
      acetylmorphine, without affecting the morphine curve. These results indicate that
      3-methoxynaltrexone selectively blocks a novel 3H-M6G binding site which is
      responsible for the analgesic actions of heroin and M6G. This ability to
      selectively antagonize heroin actions opens new possibilities in the development
      of therapeutics for the treatment of opioid abuse.

PMID- 9257685
TI  - ATR-FTIR spectroscopic investigation of E. coli transconjugants beta-lactams
      resistance phenotype.
AB  - Hyphenation of attenuated total reflection Fourier transform infrared
      spectroscopy and cluster analysis has been used to characterise a susceptible
      Escherichia coli K12 strain and the transconjugants TEM-1, TEM-2, TEM-3, SHV-2,
      SHV-3, SHV-4. A good discrimination of the susceptible strain from the
      transconjugants was obtained. Although a limited success was achieved in the
      differentiation of SHV and TEM phenotypes in general, results obtained with TEM-2
      and SHV-3 were convincing. Spectral differences observed are ascribed to the
      global effects of the conjugation process, particularly their repercussions in
      the nucleic acids and carbohydrate absorbing regions, rather than to beta
      lactamase point-mutations.

PMID- 9257687
TI  - A novel domain of fibronectin revealed by epitope mapping of a monoclonal
      antibody which inhibits fibroblasts-mediated collagen gel contraction.
AB  - The ability of cells to organize collagen fibrils is fundamental to a variety of
      processes found in embryogenesis, wound healing, fibrosis, and scar formation. We
      previously isolated a monoclonal antibody (mAb A3A5) which inhibits human
      fibroblast-mediated collagen gel contraction, an in vitro model producing the
      process of collagen morphogenesis. Human fibronectin (FN) has been shown to be
      the antigen of A3A5. The present study aimed at identifying the A3A5 epitope to
      reveal the mode of binding between collagen, FN, and fibroblasts in the process
      of gel contraction. The epitope was sought in FN fragments obtained by pepsin
      digestion and in recombinant FN fragments expressed in Escherichia coli by
      determining their immunological reactivity with A3A5, and was identified as a
      short segment consisting of the fourth through the amino half of the fifth FN
      type III. We propose a new functional domain of FN which plays a crucial role in
      the binding of fibroblasts to collagen fibrils and is involved in collagen
      morphogenesis.

PMID- 9257686
TI  - EPR spectroscopy of Escherichia coli cytochrome bo which lacks CuB.
AB  - The spectroscopic and ligand-binding properties of a copper-deficient cytochrome
      bo3, a member of the haem-copper superfamily of terminal oxidases, are reported
      and contrasted with those of the native enzyme. The enzyme lacks the copper atom
      (CuB) which is normally an integral part of the catalytic site. The consequences
      of loss of the CuB are the loss of antiferromagnetic coupling to the high-spin
      haem and an inability to form any of the integer-spin derivatives of the enzyme.
      Low-spin compounds of the normally high-spin haem are still formed with
      appropriate ligands, although these are modified.

PMID- 9257688
TI  - The activation-dependent induction of APN-(CD13) in T-cells is controlled at
      different levels of gene expression.
AB  - Recently, it was shown that aminopeptidase N (E.C. 3.4.11.2, CD13) is up
      regulated during mitogenic stimulation of peripheral T-cells. In this study, we
      demonstrate that the half-life of APN mRNA was considerably prolonged in these
      cells leading to a 2.7-fold increase of APN transcript level. The apparent half
      life time of the APN transcript was investigated by the RNA synthesis inhibitor
      chase method using actinomycin D. The steady-state APN mRNA levels was determined
      by a competitive RT-PCR. The half-lives estimated in resting T-cells, natural
      killer cells and permanently growing tumour cells varied between 3.5 and 6 h.
      Finally, nuclear run-on assays revealed that the APN gene expression of
      stimulated T-cells is controlled by increased promoter activity as well. These
      studies suggest a control of APN gene expression at the post-transcriptional
      level in addition to promoter-mediated regulation.

PMID- 9257689
TI  - Mutagenesis of two N-terminal Thr and five Ser residues in HslV, the proteolytic
      component of the ATP-dependent HslVU protease.
AB  - HslVU in E. coli is a new type of ATP-dependent protease consisting of two heat
      shock proteins: the HslU ATPase and the HslV peptidase that has two repeated Thr
      residues at its N terminus, like certain beta-type subunit of the 20S
      proteasomes. To gain an insight into the catalytic mechanism of HslV, site
      directed mutagenesis was performed to replace each of the Thr residues with Ser
      or Val and to delete the first or both Thr. Also each of the five internal Ser
      residues in HslV were replaced with Ala. The results obtained by the mutational
      analysis revealed that the N-terminal Thr acts as the active site nucleophile and
      that certain Ser residues, particularly Ser124 and Ser172, also contribute to the
      peptide hydrolysis by the HslVU protease. The mutational studies also revealed
      that both Thr, Ser103, and Ser172, but not Ser124, are involved in the
      interaction of HslV with HslU and hence in the activation of HslU ATPase as well
      as in the HslVU complex formation.

PMID- 9257690
TI  - Phytoalexin production elicited by exogenously applied jasmonic acid in rice
      leaves (Oryza sativa L.) is under the control of cytokinins and ascorbic acid.
AB  - Jasmonic acid (JA) has been shown to be a signaling compound which elicits the
      production of secondary metabolites including phytoalexins in plants. It has been
      shown that the phytoalexin production is elicited by exogenously applied JA in
      rice leaves. We now show that this phytoalexin production by exogenously applied
      JA is significantly counteracted by cytokinins, kinetin and zeatin. Kinetin and
      zeatin also inhibit the induction of naringenin-7-O-methyltransferase (a key
      enzyme in rice phytoalexin production) by JA. A natural free radical scavenger,
      ascorbic acid (AsA) shows both counteractive and enhancing effects on JA
      inducible phytoalexin production, depending on its concentration. This effect of
      AsA suggests that active oxygen species (AOS) may play important roles in
      phytoalexin production by JA in rice leaves.

PMID- 9257691
TI  - Intracellular degradation of secretion defect-type mutants of antithrombin is
      inhibited by proteasomal inhibitors.
AB  - To examine the cellular basis for secretion defect-type antithrombin deficiency,
      we expressed two mutants, P --> stop (Pro429 to stop codon) and deltaGlu
      (deletion of Glu313). Pulse-chase experiments using stably transfected BHK cells
      showed that little (< 5%) of P --> stop mutant as well as deltaGlu mutant was
      secreted and the total amount of radioactivity was significantly reduced,
      suggesting an intracellular degradation. The degradation was not inhibited by
      brefeldin A, indicating it occurring in a preGolgi apparatus. However, the
      degradation was strongly inhibited by proteasomal inhibitors, such as
      carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (LLL), carbobenzoxy-L-leucyl-L-leucyl-L
      norvalinal (LLnV) and lactacystin. By endoglycosidase H digestion and
      immunofluorescence staining, these mutants were shown to localize in the
      endoplasmic reticulum (ER). These results suggest that the secretion defect-type
      mutants of antithrombin are degraded by proteasome through the ER-associated
      quality control mechanism in the cells.

PMID- 9257692
TI  - Active oxygen species mediate the solar ultraviolet radiation-dependent increase
      in the tumour suppressor protein p53 in human skin fibroblasts.
AB  - Active oxygen species mediate many of the biological consequences of exposing
      cultured human skin cells to solar ultraviolet (UV) radiation (290-380 nm). A
      critical step in the escape from the carcinogenic potential of UV radiation is
      mediated by the protein p53. P53 activates growth arrest, allowing for DNA
      repair, and apoptosis, which removes damaged cells. Here I show that p53 in
      cultured human skin fibroblasts is elevated after treatment with hydrogen
      peroxide, an oxidant produced in cells during exposure to solar UV radiation.
      Simulated solar UV radiation increased p53, and agents that scavenge active
      oxygen species, N-acetylcysteine, ascorbate and alpha-tocopherol, inhibited the
      increase. The generation of DNA single strand breaks has been proposed to be an
      important step in the pathway leading to the increase in p53 initiated by a
      variety of cytotoxic agents. In this study I show that compounds that allow the
      accumulation of DNA single strand breaks, ara c and hydroxyurea, enhanced the UVC
      radiation (254 nm)-dependent increase in p53, but had no effect on the solar UV
      radiation-dependent increase. Thus, while DNA single strand breaks are involved
      in the UVC radiation-dependent increase in p53, the increase caused by solar UV
      radiation occurs by an alternative mechanism involving active oxygen species.

PMID- 9257693
TI  - Heme C incorporation into the c-type cytochromes FixO and FixP is essential for
      assembly of the Bradyrhizobium japonicum cbb3-type oxidase.
AB  - The monoheme and diheme c-type cytochromes FixO and FixP are two of the subunits
      of the respiratory cbb3-type oxidase of Bradyrhizobium japonicum. The cysteines
      of the respective heme C binding motifs CXXCH were changed to serines by site
      directed mutagenesis, which led to inactive oxidases in all mutants. Western blot
      analyses showed that an intact heme binding site in the FixO polypeptide is a
      prerequisite not only for the synthesis of holo-FixO protein but also for the
      formation of the entire cbb3-type oxidase complex. Both heme binding sites of
      FixP were essential for maturation and assembly of this subunit. It was not
      possible to create stable FixP variants that contained only one heme C.

PMID- 9257694
TI  - Effects of melatonin in isolated rat papillary muscle.
AB  - Melatonin (N-acetyl-5-methoxytryptamine), the principal hormone of the vertebral
      pineal gland, elicits several neurobiological effects. However, the effects of
      melatonin on cardiac muscle are still unknown. The first goal of the study was to
      investigate the role of melatonin on myocardial contractility in isolated rat
      papillary muscle using dose-response curves to melatonin, to isoproterenol and
      calcium either in the presence or in the absence of melatonin (0.3 nM). Response
      curves to isoproterenol were additionally performed in the presence of melatonin
      plus the specific receptor antagonist N-acetyltryptamine (10 microM); the
      adenylate-cyclase stimulator forskolin (10 microM) was also used. Melatonin has
      no direct inotropic effect in isolated rat papillary muscle but counteracts
      isoproterenol but not [Ca2+] effects. In fact, the EC50 for isoproterenol was
      significantly higher in the presence than in the absence of melatonin (p <
      0.001). This anti-adrenergic action occurs through an interaction to a specific
      cardiac receptor. Forskolin-stimulated adenylate cyclase induced an increase of
      contractile force (+118 +/- 25%) which was reduced in the presence of melatonin
      (+26 +/- 10%; p < 0.01). In conclusion, we found that melatonin possess anti
      adrenergic effect in isolated rat papillary muscle. This phenomenon was abolished
      in the presence of its receptor antagonist N-acetyl-tryptamine demonstrating that
      melatonin operates through a specific cardiac receptor. The reduction of
      contractility increase, induced by forskolin-stimulated adenylate cyclase, shows
      that melatonin may act through a reduction of cyclic AMP accumulation.

PMID- 9257695
TI  - Induction of chymase that forms angiotensin II in the monkey atherosclerotic
      aorta.
AB  - Chymase shows a catalytic efficiency in the formation of angiotensin (Ang) II. In
      the present study, the characterization and primary structure of monkey chymase
      were determined, and the pathophysiological role of chymase was investigated on
      the atherosclerotic monkey aorta. Monkey chymase was purified from cheek pouch
      vascular tissue using heparin affinity and gel filtration columns. The enzyme
      rapidly converted Ang I to Ang II (Km = 98 microM, k(cat) = 6203/min) but did not
      degrade several peptide hormones such as Ang II, substance P, vasoactive
      intestinal peptide and bradykinin. The primary structure, which was deduced from
      monkey chymase cDNA, showed a high homology to that of human chymase (98%). The
      mRNA levels of the aorta chymase were significantly increased in the
      atherosclerotic aorta of monkeys fed a high-cholesterol diet. These results
      indicate that monkey chymase has a highly specific Ang II-forming activity and
      may be related to the pathogenesis of atherosclerosis.

PMID- 9257696
TI  - Cell cycle specificity of Fas-mediated apoptosis in WIL-2 cells.
AB  - Antibodies to Fas/APO1 receptor induce effective apoptosis in WIL-2 cells of the
      human B-lymphoid line. Quantitative assessment of the extent of the death in
      cells synchronized by thymidine block revealed a significant increase in their
      sensitivity to the cytocidal effect mediated by Fas/APO1 during the G1 phase of
      the cell cycle. Western analysis of the content of the p53 antigen in the
      cytoplasm and nuclei of the cells showed that the Fas/APO1-induced death is
      accompanied by massive translocation of the p53 from the cytoplasm to the
      nucleus. These findings suggest that cell vulnerability to the Fas/APO1-mediated
      apoptosis is subjected to regulation by cell cycle-dependent mechanisms, one of
      which is probably the function of the p53 antigen.

PMID- 9257697
TI  - Ca-dependent regulation of Na+-selective channels via actin cytoskeleton
      modification in leukemia cells.
AB  - With the use of the patch-clamp technique, physiological mechanisms of Na+
      channel regulation involving submembranous actin rearrangements were examined in
      human myeloid leukemia K562 cells. We found that the actin-severing protein
      gelsolin applied to cytoplasmic surface of membrane fragments at a high level of
      [Ca2+]i (1 microM) increased drastically the activity of Na-selective channels of
      12 pS unitary conductance. In the experiments on intact cells, the elevation of
      [Ca2+]i using the ionophore 4Br-A23187 also resulted in Na+ channel activation.
      Addition of actin to the cytoplasmic surface of membrane patches reduced this
      activity to background level, likely due to actin polymerization. Our data imply
      that Ca-dependent modulations of the actin cytoskeleton may represent one of the
      general mechanisms of channel regulation and cell signalling.

PMID- 9257698
TI  - Potential CRE suppression by familial Alzheimer's mutants of APP independent of
      adenylyl cyclase regulation.
AB  - In familial Alzheimer's disease (FAD), mutations to I, F, and G have been
      discovered at V642 in the neuron-specific version of the amyloid precursor
      protein APP695. It has been found that expression of each FAD mutant suppresses
      the transcriptional activity of the cAMP response element CRE in a G alpha(o)
      dependent manner in a COS cell clone NK1 [Ikezu et al. (1996) EMBO J. 15, 2468
      2475]. Here we show that adenylyl cyclase (AC) inhibition is probably not the
      prerequisite for this pathway. First, expression of each FAD mutant in NK1 cells
      had no effect on AC activity stimulated by cholera toxin and by mutationally
      activated G alpha(s), although the same expression completely repressed the
      stimulated CRE. Second, a transfected activating mutant of G alpha(o) inhibited
      CRE without detectable suppression of AC, whereas similarly transfected
      activating G alpha(i2) inhibited both AC and CRE. Third, FAD mutant-induced
      inhibition occurred for CRE activity stimulated by dibutyryl cAMP. These data
      suggest that CRE suppression by FAD mutants of APP could occur independently of
      AC.

PMID- 9257699
TI  - Interaction of Fas(Apo-1/CD95) with proteins implicated in the ubiquitination
      pathway.
AB  - Fas(Apo-1/CD95), a receptor belonging to the tumor necrosis factor receptor
      family, induces apoptosis when triggered by Fas ligand. Upon its activation, the
      cytoplasmic domain of Fas binds several proteins which transmit the death signal.
      We used the yeast two-hybrid screen to isolate Fas-associated proteins. Here we
      report that the ubiquitin-conjugating enzyme UBC9 binds to Fas at the interface
      between the death domain and the membrane-proximal region of Fas. This
      interaction is also seen in vivo. UBC9 transiently expressed in HeLa cells bound
      to the co-expressed cytoplasmic segment of Fas. FAF1, a Fas-associated protein
      that potentiates apoptosis (Chu et al. (1996) Proc. Natl. Acad. Sci. USA 92,
      11894-11898), was found to contain sequences similar to ubiquitin. These results
      suggest that proteins related to the ubiquitination pathway may modulate the Fas
      signaling pathway.

PMID- 9257700
TI  - Binding mode of benzhydroxamic acid to Arthromyces ramosus peroxidase shown by X
      ray crystallographic analysis of the complex at 1.6 A resolution.
AB  - The crystal structure of Arthromyces ramosus peroxidase (ARP) in complex with
      benzhydroxamic acid (BHA) as determined by X-ray analysis at 1.6 A shows
      unambiguously how BHA binds to ARP. BHA is located in the distal heme pocket. Its
      functional groups are held by three hydrogen bonds to His56N(epsilon),
      Arg52N(epsilon), and Pro(154)O, but are too far away to interact with the heme
      iron. The aromatic ring of BHA is positioned at the entrance of the channel to
      the heme pocket, approximately parallel to the heme group. Most water molecules
      at the active site of the native enzyme are replaced by BHA, leaving a ligand,
      probably a water molecule, at the sixth position of the heme. Results are
      compared with spectroscopic data.

PMID- 9257701
TI  - Tissue-dependent upregulation of rat uncoupling protein-2 expression in response
      to fasting or cold.
AB  - The control of uncoupling protein-2 (UCP2) mRNA expression in rat brown adipose
      tissue (BAT), heart and skeletal muscles was examined. Cold exposure (48 h)
      increased UCP2 mRNA in BAT, heart and soleus muscle by 2.4-, 4.3- and 2.6-fold,
      respectively. Fasting (48 h) had no effect on UCP2 mRNA expression neither in BAT
      nor in heart, but markedly increased it in skeletal muscles. While the
      upregulation of UCP2 mRNA in response to cold exposure is in line with a putative
      uncoupling role for this protein in thermoregulatory thermogenesis, the
      unexpected upregulation of UCP2 in skeletal muscles in response to fasting seems
      inconsistent with its role as an uncoupling protein involved in dietary
      regulation of thermogenesis.

PMID- 9257702
TI  - Transferred nuclear Overhauser effect spectroscopy study of a peptide from the
      PapG pilus subunit bound by the Escherichia coli PapD chaperone.
AB  - Interaction of the Escherichia coli PapD chaperone with the synthetic peptide
      PapG308-314 (Thr-Met-Val-Leu-Ser-Phe-Pro), corresponding to the seven C-terminal
      residues of the PapG pilus subunit, was studied by transferred nuclear Overhauser
      effect (TRNOE) spectroscopy. The observation of cross-peaks corresponding to
      either intraresidue or sequential C(alpha)H/NH and C(beta)H/NH TRNOEs and the
      absence of sequential NH(i)/NH(i+1) TRNOEs indicate that the peptide binds to
      PapD in an extended conformation. In addition, line-broadening effects gave
      information of the peptide's mode of interaction with PapD. These observations
      were in excellent agreement with a recent crystal structure of a PapG peptide
      complexed with PapD.

PMID- 9257703
TI  - Channel activators regulate ATP-sensitive potassium channel (KIR6.1) expression
      in chick cardiomyocytes.
AB  - ATP-sensitive potassium channels (K(ATP)) are widely expressed and yet little is
      known about the mechanisms regulating their expression. Here we report that
      expression of chick heart Kir6.1 is regulated by channel activators. Activation
      of K(ATP) with either ATP depletion or pinacidil, up-regulated Kir6.1 mRNA 1.8-
      to 2.4-fold in cultured ventricular myocytes as measured by competitive PCR.
      Pinacidil treatment also increased Kir6.1 protein as detected using an antibody
      to Kir6.1. Glibenclamide, a K(ATP) inhibitor, completely blocked the pinacidil
      induced increase in Kir6.1 levels. It appears that Kir6.1 is up-regulated by an
      unknown signal transduction pathway initiated by K(ATP) opening.

PMID- 9257704
TI  - Expression, purification and characterization of GDP-D-mannose 4,6-dehydratase
      from Escherichia coli.
AB  - GDP-D-mannose dehydratase (GMD) catalyzes the first step of the pathway that
      converts GDP-D-mannose to GDP-L-fucose in bacteria, plants and mammals. Recently,
      the gene coding for GMD has been identified and sequenced in E. coli. Based on
      this sequence, we have expressed and purified GMD in E. coli as a glutathione
      transferase (GST) fusion protein. The fused GST-GMD protein and the thrombin
      cleaved GMD were then characterized. The catalytically active form of both enzyme
      species seems to be a hexamer of 410 and 250 kDa, respectively. The GST-GMD
      fusion protein has a Km of 0.22 +/- 0.04 mM and a specific activity of 2.3 +/-
      0.2 micromol/h/mg. Ca2+ and Mg2+ activate GMD, while GDP-L-beta-fucose, the end
      product of the pathway, inhibits it specifically. The GST-GMD fusion protein
      contains one mole of tightly bound NADP+ per mole of hexamer. Apparently, this
      NADP+ is involved in the catalytic mechanism of GMD.

PMID- 9257705
TI  - Measurement of gluconeogenesis and pyruvate recycling in the rat liver: a simple
      analysis of glucose and glutamate isotopomers during metabolism of [1,2,3
      (13)C3]propionate.
AB  - Simple equations that relate glucose and glutamate 13C-NMR multiplet areas to
      gluconeogenesis and pyruvate recycling during metabolism of [1,2,3
      (13)C3]propionate are presented. In isolated rat livers, gluconeogenic flux was
      1.2 times TCA cycle flux and about 40% of the oxaloacetate pool underwent
      recycling to pyruvate prior to formation of glucose. The 13C spectra of glucose
      collected from rats after gastric versus intravenous administration of [1,2,3
      (13)C3]propionate indicated that pyruvate recycling was slightly higher in vivo
      (49%) while glucose production was unchanged. This indicates that a direct
      measure of gluconeogenesis and pyruvate recycling may be obtained from a single
      13C-NMR spectrum of blood collected after oral administration of enriched
      propionate.

PMID- 9257707
TI  - A disulfide bond between conserved cysteines in the extracellular loops of the
      human VIP receptor is required for binding and activation.
AB  - The importance of two highly conserved cysteines in the human vasoactive
      intestinal peptide receptor I (hVIPR 1) was examined. By site-directed
      mutagenesis each Cys residue was converted into Ala or Ser. The mutant and wild
      type genes were transfected into HEK293 cells and tested for the ability to bind
      VIP and to activate cAMP production. Cys215-Ala/Ser and Cys285-Ala/Ser showed at
      least a 10-fold decrease in binding affinity and receptor potency when compared
      to the wild type. In contradiction to the wild-type receptor, both mutations were
      insensitive to dithiothreitol (DTT). The results indicate the existence of a
      disulfide bond between Cys215 and Cys285, which is important for stabilising the
      receptor in the correct conformation for ligand binding and activation.

PMID- 9257706
TI  - The glyoxysomal 3-ketoacyl-CoA thiolase precursor from Brassica napus has
      enzymatic activity when synthesized in Escherichia coli.
AB  - Glyoxysomal 3-ketoacyl-CoA thiolase is the last enzyme in the beta-oxidation of
      fatty acids in plant glyoxysomes. A full-length cDNA of the glyoxysomal 3
      ketoacyl-CoA thiolase from Brassica napus and a truncated version, lacking the N
      terminal targeting signal were cloned in a T7 promoter-based vector. Both
      recombinant proteins were expressed in Escherichia coli and activity was
      measured. Full-length and truncated 3-ketoacyl-CoA thiolase have comparable
      activity in E. coli. Moreover, full-length 3-ketoacyl-CoA thiolase was purified
      from E. coli and N-terminal sequencing of the protein confirmed that the
      precursor form indeed is enzymatically active.

PMID- 9257708
TI  - cDNA cloning of three cecropin-like antimicrobial peptides (Styelins) from the
      tunicate, Styela clava.
AB  - We cloned precursors of three new antimicrobial peptides, Styelins C, D and E,
      from a pharyngeal cDNA library of a tunicate, Styela clava. Preprostyelins
      resembled dipteran preprocecropins, while the mature domain of Styelin C
      resembled Cecropin P1, an antimicrobial peptide purified from the porcine
      intestine. Beginning with the last 6 residues of their signal sequences, Styelin
      C and Cecropin 1 from Drosophila virilis had 8/11 identical amino acids (72.7%).
      Moreover, 4 of the last 6 residues of their mature peptide domains were also
      identical. Styelins were shorter, by 8 residues, than dipteran cecropins and
      preprostyelins contained a conserved, polyanionic C-terminal extension that was
      absent in preprocecropins. Delineation of cecropin-like antimicrobial peptides in
      a protochordate supports the antiquity of this family as effectors of innate
      immunity in animals and it increases the likelihood that additional cecropin-like
      peptides will be found among other evolutionary descendants of protochordates-
      vertebrates.

PMID- 9257709
TI  - Recombinant human glycosylasparaginase catalyzes hydrolysis of L-asparagine.
AB  - Glycosylasparaginase is a lysosomal amidase involved in the degradation of
      glycoproteins. Recombinant human glycosylasparaginase is capable of catalyzing
      the hydrolysis of the amino acid L-asparagine to L-aspartic acid and ammonia. For
      the hydrolysis of L-asparagine the Km is 3-4-fold higher and Vmax 1/5 of that for
      glycoasparagines suggesting that the full catalytic potential of
      glycosylasparaginase is not used in the hydrolysis of the free amino acid. L
      Asparagine competitively inhibits the hydrolysis of aspartylglucosamine
      indicating that both the amino acid and glycoasparagine are interacting with the
      same active site of the enzyme. The hydrolytic mechanism of L-asparagine and
      glycoasparagines will be discussed.

PMID- 9257710
TI  - CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia
      cells.
AB  - Treatment of U937 cells with dolichyl phosphate led to an increase in the
      activity of the ICE family protease CPP32, accompanied with cleavage of pre-CPP32
      to generate p17. Peptide inhibitors YVAD-cmk and Z-Asp-CH2-DCB (specific to ICE)
      and DEVD-CHO (specific to CPP32) blocked the dolichyl phosphate-induced
      apoptosis. The dolichyl phosphate-induced increase of CPP32 activity was
      inhibited by adenylate cyclase inhibitors, SQ 22536 and 2',5'-dideoxyadenosine.
      Dolichyl phosphate caused a transient increase of intracellular cAMP
      concentration. The results suggest that modulation of cAMP synthesis due to the
      stimulation of adenylate cyclase by dolichyl phosphate plays a critical role in
      CPP32 activation and apoptosis.

PMID- 9257711
TI  - Stimulation of respiration by methylene blue in rat liver mitochondria.
AB  - The effect of methylene blue on isolated rat liver mitochondria in the presence
      and absence of chloroacetaldehyde was investigated. Fatty acid oxidation was
      inhibited by chloroacetaldehyde and subsequently stimulated by methylene blue.
      Assessment of tightly coupled mitochondria revealed decreasing respiratory
      control ratios induced by increasing concentrations of methylene blue and
      methylene blue provoked mitochondrial swelling. In uncoupled mitochondria,
      methylene blue promoted a concentration-dependent stimulation of respiration.
      These findings provide evidence that methylene blue, the redox dye currently used
      as an antidote for encephalopathy associated with alkylating chemotherapy,
      uncouples oxidative phosphorylation and acts as an electron transfer mediator to
      stimulate mitochondrial respiration.

PMID- 9257713
TI  - Acylphosphate formation by the Menkes copper ATPase.
AB  - The Menkes ATPase is the product of the MNK gene, defective in some inherited
      human disorders of copper metabolism. We here show the formation of an
      acylphosphate intermediate by the murine MNK homologue in membranes from normal
      and copper resistant Chinese hamster ovary cells. In the latter, fivefold higher
      levels of acylphosphate were formed. Challenging these cells with copper, which
      induces relocation of the MNK ATPase from the trans-Golgi network to the plasma
      membrane, did not influence acylphosphate formation. The kinetics of
      phosphorylation, metal dependence, and sensitivity to inhibitors were
      investigated. The results show that the MNK ATPase is an active P-type ATPase and
      provide a direct functional test for this enzyme.

PMID- 9257712
TI  - Multiple tyrosine residues in the intracellular domain of the common beta subunit
      of the interleukin 5 receptor are involved in activation of STAT5.
AB  - In contrast to the general model of cytokine-induced JAK/STAT signaling, tyrosine
      phosphorylation of the IL-5R beta chain seems to be dispensable for STAT
      activation in cells overexpressing exogenous STAT proteins. In this study we
      expressed IL-5 receptor mutants in 293 cells and studied IL-5-induced endogenous
      STAT-dependent transcription. Our results indicate that: (a) tyrosine
      phosphorylation of the IL-5R beta chain is required for endogenous STAT5
      activation, (b) multiple tyrosine residues are phosphorylated upon IL-5
      stimulation, including Tyr577, Tyr612, Tyr695, and Tyr750, and (c) Tyr612,
      Tyr695, and Tyr750 are all capable of inducing activation of STAT5, demonstrating
      a high level of functional redundancy within the IL-5R beta chain.

PMID- 9257714
TI  - Binding of TNP-ATP and TNP-ADP to the non-catalytic sites of Escherichia coli F1
      ATPase.
AB  - Using site-directed-tryptophan fluorescence, parameters for equilibrium binding
      of (Mg)TNP-ATP and (Mg)TNP-ADP to non-catalytic sites of Escherichia coli F1
      ATPase were determined. All three non-catalytic sites showed the same affinity
      for MgTNP-ATP (Kd = 0.2 microM) or MgTNP-ADP (Kd = 6.5 microM) whereas even at
      concentrations of 100 microM no binding of uncomplexed TNP-ATP or TNP-ADP was
      observed. The results demonstrate that the three non-catalytic sites bind TNP
      nucleotides non-cooperatively, and emphasize the importance of Mg2+ for non
      catalytic-site nucleotide binding. Parameters for binding of (Mg)TNP-ADP to the
      three catalytic sites were also determined, and showed marked cooperativity. This
      work completes the set of thermodynamic parameters for equilibrium binding of
      (Mg)TNP-ATP and (Mg)TNP-ADP to all six nucleotide sites of F1, providing
      essential information to fully exploit the potential of these nucleotide analogs
      in studies of F1-ATPase.

PMID- 9257715
TI  - Thyroxine induces cyclosporin A-insensitive, Ca2+-dependent reversible
      permeability transition pore in rat liver mitochondria.
AB  - The effect of thyroxine on Ca2+-dependent mitochondrial permeability transition
      has been examined. It is shown that 40 microM thyroxine induces high amplitude
      swelling and decrease in membrane potential in Ca2+-loaded rat liver
      mitochondria, both in the presence and absence of cyclosporin A. Thyroxine
      induced decrease in membrane potential is partially or completely reversed by
      addition of EGTA into the incubation medium. Nigericin and ADP are shown to
      prevent, or significantly delay, the effects of thyroxine on both mitochondrial
      swelling and membrane potential, whereas nicotinamide potentiates the
      permeabilisation of mitochondria. It is suggested that thyroxine induced
      reversible, cyclosporin A-insensitive permeability transition pore (PTP) opening
      in the inner mitochondrial membrane.

PMID- 9257716
TI  - The pH-dependent reciprocal changes in contributions of ADP/ATP antiporter and
      aspartate/glutamate antiporter to the fatty acid-induced uncoupling.
AB  - The pH effect on carboxyatractylate-, glutamate- and aspartate-induced recoupling
      of palmitate-uncoupled rat liver mitochondria has been studied. Stimulation of
      respiration by low palmitate concentrations (5-20 microM) in the presence of 3 mM
      MgCl2 is shown to be pH-independent within the 7.0-7.8 range. The recoupling
      effect of glutamate (or aspartate) decreases and that of carboxyatractylate
      increases with increase in pH. The recoupling effect of a combination of
      carboxyatractylate and glutamate (aspartate) appears to be constant at these pH
      values, being as high as about 80%. It is concluded that uncoupling by low
      palmitate in liver mitochondria is mediated mainly by ATP/ADP and
      aspartate/glutamate antiporter.

PMID- 9257717
TI  - vesl, a gene encoding VASP/Ena family related protein, is upregulated during
      seizure, long-term potentiation and synaptogenesis.
AB  - We have isolated a novel cDNA, vesl, that was induced during convulsive seizure
      in the rat hippocampus. The vesl gene encodes a protein of 186 amino acids that
      has significant homology to the EVH1 domain of the VASP/Ena family of proteins
      implicated in the control of microfilament dynamics. The expression of vesl mRNA
      was induced in the granule cell layer during persistent long-term potentiation
      (LTP) of the dentate gyrus in an NMDA receptor-dependent manner. Furthermore,
      vesl mRNA was expressed at a high level during hippocampal synaptogenesis. We
      suggest that the Vesl protein may be involved in the structural changes that
      occur at synapses during long-lasting neuronal plasticity and development.

PMID- 9257718
TI  - Amino acid sequence and three-dimensional structure of the Tn-specific isolectin
      B4 from Vicia villosa.
AB  - The partial amino acid sequence of the tetrameric isolectin B4 from Vicia villosa
      seeds has been determined by peptide analysis, and its three-dimensional
      structure solved by molecular replacement techniques and refined at 2.9 A
      resolution to a crystallographic R-factor of 21%. Each subunit displays the
      thirteen-stranded beta-barrel topology characteristic of legume lectins. The
      amino acid residues involved in metal- and sugar-binding are similar to those of
      other GalNAc-specific lectins, indicating that residues outside the carbohydrate
      binding pocket modulate the affinity for the Tn glycopeptide. Isolectin B4
      displays an unusual quaternary structure, probably due to protein glycosylation.

PMID- 9257719
TI  - Phosphocholine and sphingosine-1-phosphate synergistically stimulate DNA
      synthesis by a MAP kinase-dependent mechanism.
AB  - We have previously shown that in NIH 3T3 fibroblasts phosphocholine (PCho)
      potentiates sphingosine-1-phosphate (S1P)-induced mitogenesis. Here we report
      that PCho and S1P also synergistically stimulate DNA synthesis in mouse Swiss 3T3
      fibroblasts and in mouse JB6 epidermal cells. The combined actions of PCho and
      S1P on DNA synthesis were associated with synergistic activation of the p42/p44
      mitogen-activated protein (MAP) kinases. Ethanolamine (50-100 microM) further
      enhanced the synergistic effects of PCho and SIP on DNA synthesis but not on MAP
      kinase activity. The results indicate that the synergistic mitogenic effects of
      PCho and S1P (i) are not restricted to NIH 3T3 fibroblasts, (ii) are
      predominantly mediated by the MAP kinase-dependent signal transduction pathway,
      and (iii) are enhanced by ethanolamine via a MAP kinase-independent mechanism.

PMID- 9257720
TI  - MDR-1 gene expression is a minor factor in determining the multidrug resistance
      phenotype of MCF7/ADR and KB-V1 cells.
AB  - The relevance of MDR-1 gene expression to the multidrug resistance phenotype was
      investigated. Drug-resistant cells, KB-V1 and MCF7/ADR, constantly expressed mRNA
      of the MDR-1 gene and were more resistant to vinblastine and adriamycin than drug
      sensitive cells, KB-3-1 and MCF7. The drug efflux rate of KB-V1 was the same as
      KB-3-1 although the MDR-1 gene was expressed in only the resistant cell. The
      higher intracellular drug concentration of KB-3-1 than KB-V1 was due to the large
      drug influx. In the case of MCF7 and MCF7/ADR, the influx and efflux of the drug
      had nearly the same pattern and drug efflux was not affected by verapamil. The
      amount of ATP, cofactor of drug pumping activity of P-glycoprotein, was not
      changed by the resistance. These observations suggested that drug efflux mediated
      by MDR-1 gene expression was not a major determining factor of drug resistance in
      the present cell systems, and that the drug resistance could be derived from the
      change in drug uptake and other mechanisms.

PMID- 9257721
TI  - Fatty acids induced uncoupling of Saccharomyces cerevisiae mitochondria requires
      an intact ADP/ATP carrier.
AB  - Fatty acids stimulate the oxidation rate of mitochondria isolated from the wild
      type Saccharomyces cerevisiae, but do not affect significantly the respiration of
      mitochondria isolated from mutants, in which the ADP/ATP carrier (AAC) was either
      modified (R96H) or deleted (delta aac2). Similarly as in mammalian mitochondria,
      the transmembrane electrical potential difference (delta psi) in the wild-type
      yeast mitochondria was dissipated by low concentrations of free fatty acids, and
      this was partially inhibited by bongkrecate. In contrast to the wild-type
      mitochondria, the addition of increasing concentrations of fatty acids to the op1
      (R96H) mutant mitochondria abolished only a small portion of delta psi, as
      compared to the change induced by classical uncouplers. The different effects of
      fatty acids on both, the respiration and the delta psi of mitochondria isolated
      from the wild-type and the aac mutants, respectively, demonstrates that the
      intact AAC is essential for the fatty acids induced H+ permeability of
      mitochondrial membrane.

PMID- 9257722
TI  - Disulfide-bonding between Drosophila laminin beta and gamma chains is essential
      for alpha chain to form alpha betagamma trimer.
AB  - Assembly of Drosophila laminin alpha, beta and gamma chains was analyzed by
      immunoprecipitation of the lysate from metabolically radiolabeled Kc 167 cells
      with chain-specific antibodies followed by two dimensional electrophoresis in
      which non-reducing and reducing SDS gel electrophoresis are combined.
      Precipitation of monomeric beta (or gamma) with anti-gamma (or -beta) antibody
      revealed that beta and gamma form stable dimer before they are disulfide-bonded
      to each other. In contrast, alpha associates with neither monomeric beta,
      monomeric gamma nor betagamma dimer without disulfide-bonding but only with
      disulfide-bonded betagamma dimer to form alpha betagamma trimers. These results
      thus demonstrated that the interchain disulfide-boding between beta and gamma is
      essential for alpha to form alpha betagamma trimer. We also found that the alpha
      betagamma trimer can be secreted with alpha chain either disulfide-bonded or not
      bonded to the disulfide-bonded betagamma dimer.

PMID- 9257723
TI  - Three-dimensional structure of Serratia marcescens nuclease at 1.7 A resolution
      and mechanism of its action.
AB  - The three-dimensional crystal structure of Serratia marcescens (Sm) nuclease has
      been refined at 1.7 A resolution to the R-factor of 17.3% and R-free of 22.2%.
      The final model consists of 3678 non-hydrogen atoms and 443 water molecules. The
      analysis of the secondary and the tertiary structures of the Sm nuclease suggests
      a topology which reveals essential inner symmetry in all the three layers forming
      the monomer. We propose the plausible mechanism of its action based on a
      concerted participation of the catalytically important amino acid residues of the
      enzyme active site.

PMID- 9257724
TI  - Evidence for a role of C-terminal amino acid residues in skeletal muscle Ca2+
      release channel (ryanodine receptor) function.
AB  - The effects of deleting 1, 3 and 15 amino acid residues from the highly conserved
      C-terminus of the tetrameric skeletal muscle ryanodine receptor (RyR) complex
      were determined. Immunoblot analysis indicated similar expression levels in
      HEK293 cells for full-length and mutant proteins. Full-length and RyR lacking the
      last amino acid showed [3H]ryanodine binding and single channel activities
      typical of native receptors. Deletion of 3 amino acids resulted in decreased
      activities, whereas deletion of 15 amino acids yielded an inactive RyR. These
      results suggest that the most 15 C-terminal amino acids are important for the
      expression of a functional RyR complex.

PMID- 9257726
TI  - Sterol 22-desaturase, cytochrome P45061, possesses activity in xenobiotic
      metabolism.
AB  - CYP61 was revealed in the sequencing of the yeast genome on chromosome XIII and
      was the last member of the CYP superfamily in yeast to be discovered. We show
      here that besides the housekeeping role in 22-desaturation during ergosterol
      biosynthesis the enzyme is also that responsible for benzo(a)pyrene
      metabolism/promutagen activation by yeast in genotoxicity assays. This enzyme may
      represent an ancestral activity for the superfamily which allowed xenobiotic
      metabolism for the first time.

PMID- 9257725
TI  - ADP-ribosylation of tuftsin suppresses its receptor-binding capacity and
      phagocytosis-stimulating activity to murine peritoneal macrophages.
AB  - Arginine-specific ADP-ribosyltransferase present in granules of chicken
      polymorphonuclear leukocytes (so-called heterophils) is released into the
      extracellular space by stimulus of calcium ionophore A23187 or opsonized zymosan
      [Terashima et al. (1996) J. Biochem. 120, 1209-1215]. In the present work, we
      examined extracellular targets of the released transferase and identified
      tuftsin, a phagocytosis-stimulating tetrapeptide derived from leukokinin, as a
      preferential substrate of the enzyme in chicken plasma. Specific binding of FITC
      tuftsin to murine peritoneal macrophages, observed under a fluorescent
      microscope, was impaired by ADP-ribosylation of the labelled peptide. Phagocytic
      assay analyzed by flow cytometry revealed that ADP-ribosylation of tuftsin
      decreased its phagocytosis-stimulating activity towards the macrophages. Thus,
      the ADP-ribosylation of tuftsin apparently decreases its biological activity and
      ADP-ribosylation may possibly be involved in inflammatory processes through
      alterations in tuftsin activity.

PMID- 9257727
TI  - Ion channels in the vacuoles of the seagrass Posidonia oceanica.
AB  - Voltage-dependent ionic channels were investigated by the patch-clamp technique
      in the vacuolar membrane from the leaves of the seagrass Posidonia oceanica.
      Vacuoles extruded from the meristematic white part of the leaves displayed
      rectifying slow currents which activated in several seconds at positive
      potentials and deactivated at negative voltages within a few hundreds of ms. Like
      the Slow Vacuolar (SV) channel already identified in the tonoplast of terrestrial
      plants, the SV voltage-dependent channel of Posidonia leaves was activated by
      micromolar concentrations of Ca2+ and was equally permeable to K+ and Na+. The
      single-channel conductance of the Posidonia SV-type channel was 106 +/- 12 pS (in
      symmetric 400 mM K+). In the same ionic solutions, another channel, occasionally
      observed in vacuoles from the green part of the leaves, displayed a single
      channel conductance of 47 +/- 4 pS. To our knowledge, this is the first
      electrophysiological characterization of ion transport pathways in Posidonia, a
      marine plant of crucial importance for the ecology of the Mediterranean sea.

PMID- 9257728
TI  - Kinetics of antifreeze protein-induced ice growth inhibition.
AB  - Antifreeze proteins (AFPs) depress the freezing temperature of a solution in a
      non-colligative manner, by arresting the growth of ice crystals. The kinetics of
      this effect, studied here for the first time using a new technique called
      temperature gradient thermometry, are consistent with an adsorption-mediated
      inhibitory mechanism. The results obtained by this approach provide a new
      experimental basis for understanding AFP interaction with ice.

PMID- 9257729
TI  - Aromatic amino acid methyl ester analogs form quinonoidal species with Dopa
      decarboxylase.
AB  - This study reports for the first time that binding of aromatic methyl ester
      analogs to Dopa decarboxylase in the native and inactive nicked forms causes the
      appearance of a dead-end quinonoidal species absorbing at 500 nm, in addition to
      an external aldimine absorbing at 398 nm. The equilibrium mixture of these
      species varies depending on both the analog structure and the enzyme form. The
      above mentioned intermediates are also characterized with respect to their CD
      properties and the equilibria for their formation are determined as a function of
      pH. The results have provided evidence that the establishment of proper contacts
      between the active site and hydroxyl groups of the ligand are indispensable in
      order to limit unwanted side reactions.

PMID- 9257730
TI  - Expression of cartilage oligomeric matrix protein by human synovium.
AB  - Human synovium was analyzed for the possible expression of cartilage oligomeric
      matrix protein (COMP). Immunostaining with polyclonal antiserum to COMP
      demonstrated positive staining within the synovial cells and immediately
      subjacent connective tissue, with less intense staining in the deeper connective
      tissue. Western blot analysis using either polyclonal or monoclonal antibodies to
      human COMP confirmed the presence of COMP by immunoreactive bands with the same
      molecular mass (approximately 110 kDa) as purified articular cartilage COMP. PCR
      using oligonucleotides that span human COMP exons 7-13 revealed identical
      amplification products from cDNA prepared from either human chondrocytes or
      synovium. Northern blot analysis using a biotinylated-probe to human COMP,
      spanning exons 12-13, also reveal an identical hybridization product to either
      human chondrocyte or synovium total RNA. Human synovium should be considered as a
      potential tissue source of COMP in any investigation of biological markers of
      cartilage metabolism.

PMID- 9257731
TI  - Nociceptin/orphanin FQ stimulates extracellular acidification and desensitization
      of the response involves protein kinase C.
AB  - A Chinese hamster ovary (CHO) cell line, CHO-ORL1, stably expressing human opioid
      receptor-like receptor 1 (ORL1) has been used to determine ORL1-mediated
      signaling events using microphysiometry. Nociceptin/orphanin FQ (N/OFQ), a
      specific endogenous agonist of ORL1, induced an increase in extracellular
      acidification rate (ECAR) in CHO-ORL1 cells. The ECAR response stimulated by
      N/OFQ was concentration-dependent and pertussis toxin-sensitive. Repeated
      exposures of the cells to N/OFQ caused desensitization of ORL1. The ECAR response
      was recovered at the half-life of approximately 12 min after the initial
      challenge. Pretreatment with inhibitor of cAMP-dependent kinase did not affect
      desensitization of ORL1. However, specific inhibitors for protein kinase C almost
      abolished N/OFQ-induced desensitization of extracellular acidification
      responsiveness, indicating the involvement of protein kinase C in the process.

PMID- 9257732
TI  - Isolation of Candida species on media with and without added fluconazole reveals
      high variability in relative growth susceptibility phenotypes.
AB  - Mouthwashes from human immunodeficiency virus-positive individuals were sampled
      for yeasts by direct plating on a differential agar medium with and without added
      fluconazole and via enrichment broths with and without added fluconazole. The
      colonies of the yeasts isolated were tested for relative growth in the presence
      of single concentrations of itraconazole and fluconazole. Among 258 culture
      plates containing yeasts obtained via different isolation routes from 86 yeast
      positive samples, 33 (12.7%) of the plates showed unexpectedly high colony-to
      colony variation in relative growth. Intercolony variation was seen in 41 (47.7%)
      of the 86 isolates when relative growth data were analyzed for all colonies of an
      isolate tested, regardless of the medium used for isolation. The prevalence of
      relative growth variability with the azoles was highest for Candida glabrata
      (100% of 13 isolates), followed by Candida krusei (60% of 5 isolates) and Candida
      albicans (40% of 53 isolates), and the visual patterns of variability seen in
      scatter plots of the data showed species specificity. Relative growth phenotypes
      generally tended to be stable for each yeast colony in subcultures, whether or
      not the medium used for subculture contained antifungal agents. DNA
      fingerprinting of stable and variable C. albicans isolates showed changes in band
      patterns detected with the probe Ca3, suggesting that the variability may have
      resulted from selection of different subtypes of the yeasts during the isolation
      procedure. These findings suggest that the yeasts isolated from single clinical
      samples were often not clonal in nature. The relative growth test revealed colony
      variability more readily than conventional susceptibility testing.

PMID- 9257733
TI  - Assessment of biliary excretion of piperacillin-tazobactam in humans.
AB  - Piperacillin-tazobactam concentrations in serum and bile were measured
      intraoperatively in 10 patients undergoing cholecystectomy (group 1) and 5
      cholecystectomized patients provided with external bile duct drainage (group 2).
      Each patient received a single intravenous dose of piperacillin at 4 g plus
      tazobactam at 0.5 g over 30 min. Drug concentrations in both serum and bile were
      measured by high-performance liquid chromatography. In group 1 patients, serum
      and bile specimens and gallbladder wall fragments were collected at mean times of
      70 and 83 min postinfusion, respectively. The mean concentrations of piperacillin
      and tazobactam were, respectively, 69.1 +/- 41.5 (standard deviation) and 9.9 +/-
      5.1 microg/ml in serum, 630.4 microg/ml (range, 24.8 to 1,194 microg/ml) and 11.8
      microg/ml (range, 3.6 to 22 microg/ml) in choledochal bile, 342.3 microg/ml
      (range, 1.1 to 1,149 microg/ml) and 7.7 microg/ml, (range, 0.2 to 23.1 microg/ml)
      in gallbladder bile, and 49.3 microg/g (range, 9.7 to 223 microg/g) and 2.9
      microg/g (range, 0.1 to 5.9 microg/g) in the gallbladder wall. In group 2
      patients, the amounts of drugs recovered in bile drainage obtained over 12 h were
      28.4 +/- 18.0 and 1.0 +/- 0.5 mg for piperacillin and tazobactam, respectively.
      Peak piperacillin and tazobactam concentrations in bile reached 358 +/- 242 and
      10.8 +/- 4.2 microg/ml, respectively. Comparison of drug levels in serum and bile
      suggests an underlying active secretion process for piperacillin elimination into
      the bile, unlike that of tazobactam. From a therapeutic viewpoint, given the
      concentrations of tazobactam recorded in bile fluid and tissue, the addition of
      this beta-lactamase inhibitor to piperacillin therapy might be of interest in the
      management of biliary tract infections, mostly in patients at risk of mixed
      aerobic-anaerobic infections due to beta-lactamase-producing organisms.

PMID- 9257734
TI  - Variability of chromosomally encoded beta-lactamases from Klebsiella oxytoca.
AB  - The beta-lactamase genes of Klebsiella oxytoca were previously divided into two
      main groups: bla(OXY-1) and bla(OXY-2). The two beta-lactamase groups were each
      represented by beta-lactamases with four different pIs. In each group, one form
      of beta-lactamase is more frequent than the others combined. The beta-lactamase
      gene of each representative beta-lactamase with a different pI that was not yet
      sequenced (pIs 5.7, 6.8 [OXY-2], 7.1, 8.2, and 8.8 [OXY-1]) was cloned and
      sequenced. The susceptibility patterns as well as relative rates and kinetic
      parameters for beta-lactam hydrolysis revealed that OXY-2 enzymes hydrolyzed
      several of the beta-lactams that were examined (carbenicillin, cephalothin,
      cefamandole, ceftriaxone, and aztreonam) at a greater rate than the OXY-1 enzymes
      did. Comparison of K. oxytoca beta-lactamases with plasmid-mediated extended
      spectrum beta-lactamases MEN-1 and TOHO-1 implied that the threonine at position
      168 present in OXY-2 beta-lactamase instead of the alanine in OXY-1 could be
      responsible for its modified substrate hydrolysis. In each group, the beta
      lactamase with a variant pI differs from the main form of beta-lactamase by one
      to five amino acid substitutions. The substrate profile and the 50% inhibitory
      concentrations revealed that all substitutions differing from the main form of
      beta-lactamase were neutral except one difference in the OXY-1 group. This
      substitution of an Ala to a Gly at position 237 increases the hydrolysis of some
      beta-lactams, particularly aztreonam; decreases the hydrolysis of
      benzylpenicillin, cephaloridine, and cefamandole, and decreases the
      susceptibility to clavulanic acid (fivefold increase in the 50% inhibitory
      concentration).

PMID- 9257736
TI  - Synthesis and antitrypanosomal activities of a series of 7-deaza-5'
      noraristeromycin derivatives with variations in the cyclopentyl ring
      substituents.
AB  - Previous work in our laboratories has suggested that (+)-5'-nor-7
      deazaaristeromycin (compound 1) may represent a prototype structure for a series
      of compounds with significant antitrypanosomal activities. To test this
      possibility, a series of derivatives of compound 1 with changes in the
      cyclopentyl substituents (compounds 3 to 10) have been studied. Although some
      growth activity was obtained with the L-like compound 5, related compounds 3 and
      7 had little or no activity below 100 microM. D-like compounds 4 and 6 showed
      some activity at or below 100 microM, but the most interesting finding was that
      both the D- and L-like compounds having a methyl substituent on the 4' position
      were most active.

PMID- 9257735
TI  - Structure-activity relationship of carbacephalosporins and cephalosporins:
      antibacterial activity and interaction with the intestinal proton-dependent
      dipeptide transport carrier of Caco-2 cells.
AB  - An intestinal proton-dependent peptide transporter located on the lumenal surface
      of the enterocyte is responsible for the uptake of many orally absorbed beta
      lactam antibiotics. Both cephalexin and loracarbef are transported by this
      mechanism into the human intestinal Caco-2 cell line. Forty-seven analogs of the
      carbacephalosporin loracarbef and the cephalosporin cephalexin were prepared to
      evaluate the structural features necessary for uptake by this transport carrier.
      Compounds were evaluated for their antibacterial activities and for their ability
      to inhibit 1 mM cephalexin uptake and, subsequently, uptake into Caco-2 cells.
      Three clinically evaluated orally absorbed carbacephems were taken up by Caco-2
      cells, consistent with their excellent bioavailability in humans. Although the
      carrier preferred the L stereoisomer, these compounds lacked antibacterial
      activity and were hydrolyzed intracellularly in Caco-2 cells. Compounds modified
      at the 3 position of cephalexin and loracarbef with a cyclopropyl or a
      trifluoromethyl group inhibited cephalexin uptake. Analogs with lipophilic groups
      on the primary amine of the side chain inhibited cephalexin uptake, retained
      activity against gram-positive bacteria but lost activity against gram-negative
      bacteria. Substitution of the phenylglycl side chain with phenylacetyl side
      chains gave similar results. Compounds which lacked an aromatic ring in the side
      chain inhibited cephalexin uptake but lost all antibacterial activity. Thus, the
      phenylglycl side chain is not absolutely required for uptake. Different
      structural features are required for antibacterial activity and for being a
      substrate of the transporter. Competition studies with cephalexin indicate that
      human intestinal Caco-2 cells may be a useful model system for initially guiding
      structure-activity relationships for the rational design of new oral agents.

PMID- 9257737
TI  - Levofloxacin versus ciprofloxacin, flucloxacillin, or vancomycin for treatment of
      experimental endocarditis due to methicillin-susceptible or -resistant
      Staphylococcus aureus.
AB  - Levofloxacin is the L isomer of ofloxacin, a racemic mixture in which the L
      stereochemical form carries the antimicrobial activity. Levofloxacin is more
      active than former quinolones against gram-positive bacteria, making it
      potentially useful against such pathogens. In this study, levofloxacin was
      compared to ciprofloxacin, flucloxacillin, and vancomycin for the treatment of
      experimental endocarditis due to two methicillin-susceptible Staphylococcus
      aureus (MSSA) and two methicillin-resistant S. aureus (MRSA) isolates. The four
      test organisms were susceptible to ciprofloxacin, the levofloxacin MICs for the
      organisms were low (0.12 to 0.25 mg/liter), and the organisms were killed in
      vitro by drug concentrations simulating both the peak and trough levels achieved
      in human serum (5 and 0.5 mg/liter, respectively) during levofloxacin therapy.
      Rats with aortic endocarditis were treated for 3 days. Antibiotics were injected
      with a programmable pump to simulate the kinetics of either levofloxacin (350 mg
      orally once a day), ciprofloxacin (750 mg orally twice a day), flucloxacillin (2
      g intravenously four times a day), or vancomycin (1 g intravenously twice a day).
      Levofloxacin tended to be superior to ciprofloxacin in therapeutic experiments (P
      = 0.08). More importantly, levofloxacin did not select for resistance in the
      animals, in contrast to ciprofloxacin. The lower propensity of levofloxacin than
      ciprofloxacin to select for quinolone resistance was also clearly demonstrated in
      vitro. Finally, the effectiveness of this simulation of oral levofloxacin therapy
      was at least equivalent to that of standard treatment for MSSA or MRSA
      endocarditis with either flucloxacillin or vancomycin. This is noteworthy,
      because oral antibiotics are not expected to succeed in the treatment of severe
      staphylococcal infections. These good results obtained with animals suggest that
      levofloxacin might deserve consideration for further study in the treatment of
      infections due to ciprofloxacin-susceptible staphylococci in humans.

PMID- 9257738
TI  - Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate.
AB  - In an open, randomized, triple crossover study, the effects of cisapride and
      sucralfate on the pharmacokinetics of sparfloxacin were assessed. Fifteen healthy
      volunteers received 400 mg of sparfloxacin as a single oral dose on day 0. In a
      random order, concomitant doses of 10 mg of cisapride three times daily from day 
      2 to day 2 and 1 g of sucralfate four times daily from day -2 to day 0 were
      administered. Sparfloxacin concentrations were measured by bioassay and high
      performance liquid chromatography. Pharmacokinetic parameters for sparfloxacin
      alone were as follows (mean +/- standard deviation): maximum concentration of
      drug in serum (C(max)), 1.27 +/- 0.39 microg/ml; time to C(max) (T(max)), 4.1 +/-
      1.9 h; area under the concentration-time curve (AUC), 35.0 +/- 9.7 microg x h/ml;
      mean residence time, 28.5 +/- 5.7 h; half-life (t1/2), 20 +/- 4 h; urinary
      recovery (UR x f), 11.0% +/- 2.7%; and metabolite-sparfloxacin ratio in urine,
      2.6. For the cisapride group there was a significant decrease in the sparfloxacin
      T(max) (1.9 +/- 2.1 h) and a significant increase in C(max) (1.74 +/- 0.73
      microg/ml). The QTc interval for patients receiving sparfloxacin and cisapride
      was prolonged by 7.7% compared to the QTc interval during medication-free
      periods. Significant differences in the values for the group receiving sucralfate
      compared to the values for the group receiving sparfloxacin alone were found:
      C(max), 0.77 +/- 0.31 microg/ml; AUC, 18.6 +/- 5.8 microg x h/ml; t1/2, 26 +/- 10
      h; and UR x f, 5.8 +/- 1.8%. Concomitant adminstration of cisapride accelerates
      the absorption and increases the peak concentration of sparfloxacin without
      having a significant effect on the extent of bioavailability. Coadministration of
      sucralfate leads to a 44% decrease in the bioavailability of sparfloxacin.

PMID- 9257739
TI  - Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group
      streptococcus experimental endocarditis.
AB  - The efficacy of azithromycin or clarithromycin was compared to that of
      amoxicillin, clindamycin, or erythromycin for the prevention of viridans group
      streptococcus experimental endocarditis. Rabbits with catheter-induced aortic
      valve vegetations were given no antibiotics or two doses of amoxicillin at 25
      mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg,
      clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at
      10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous
      infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after
      bacterial inoculation, the rabbits were killed and aortic valve vegetations were
      aseptically removed and cultured for bacteria. Infective endocarditis occurred in
      88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals
      receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals
      receiving clarithromycin, and 1% of animals receiving azithromycin. All five
      regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was
      less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or
      clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for
      the prevention of viridans group streptococcus experimental endocarditis in this
      model.

PMID- 9257740
TI  - Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB
      mutations.
AB  - Ethambutol [(S,S')-2,2'-(ethylenediimino)di-1-butanol; EMB], is a first-line drug
      used to treat tuberculosis. To gain insight into the molecular basis of EMB
      resistance, we characterized the 10-kb embCAB locus in 16 EMB-resistant and 3 EMB
      susceptible genetically distinct Mycobacterium tuberculosis strains from diverse
      localities by automated DNA sequencing and single-stranded conformation
      polymorphism analysis. All 19 organisms had virtually identical sequences for the
      entire 10-kb region. Eight EMB-resistant organisms had mutations located in codon
      306 of embB that resulted in the replacement of the wild-type Met residue with
      Ile or Val. Automated sequence analysis of the 5' region (1,892 bp) of embB in an
      additional 69 EMB-resistant and 30 EMB-susceptible M. tuberculosis isolates from
      diverse geographic localities and representing 70 distinct IS6110 fingerprints
      confirmed the unique association of substitutions in amino acid residue 306 of
      EmbB with EMB resistance. Six other embB nucleotide substitutions resulting in
      four amino acid replacements were uniquely found in resistant strains. Sixty-nine
      percent of epidemiologically unassociated EMB-resistant organisms had an amino
      acid substitution not found in susceptible strains, and most (89%) replacements
      occurred at amino acid residue 306 of EmbB. For strains with the Met306Leu or
      Met306Val replacements EMB MICs were generally higher (40 microg/ml) than those
      for organisms with Met306Ile substitutions (20 microg/ml). The data are
      consistent with the idea that amino acid substitutions in EmbB alter the drug
      protein interaction and thereby cause EMB resistance.

PMID- 9257741
TI  - Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin
      1 production by Staphylococcus aureus in both logarithmic and stationary phases
      of growth.
AB  - Production of exotoxins by staphylococci and streptococci may lead to the
      development of toxic shock syndrome (TSS). Because clindamycin inhibits exotoxin
      production, its use has been advocated for the treatment of TSS. However, the
      bacteriostatic action of clindamycin might be a disadvantage for the treatment of
      overwhelming infections. We investigated the effects of flucloxacillin and
      gentamicin on exotoxin production, because incubation with these antibiotics
      combines bactericidal action with protein synthesis inhibition. Staphylococcus
      aureus during the logarithmic and stationary phases of growth was incubated with
      either clindamycin, flucloxacillin, or a combination of flucloxacillin and
      gentamicin at concentrations of 2 or 10 times the MIC. In logarithmic-phase
      cultures clindamycin had a static effect on bacterial growth. After incubation
      with flucloxacillin, either alone or in combination with gentamicin, a rapid and
      large reduction in the number of viable bacteria was demonstrated. In stationary
      phase cultures none of the antibiotics significantly changed the number of viable
      bacteria. TSS toxin 1 (TSST-1) production during logarithmic-phase growth was
      inhibited by > or =95% by all antibiotics. In stationary-phase cultures,
      clindamycin, flucloxacillin, and the combination of flucloxacillin and gentamicin
      inhibited TSST-1 production by 95, 30, and 75%, respectively, compared with the
      level of exotoxin production in the controls. The present results indicate that
      clindamycin inhibits TSST-1 production and exerts bacteriostatic activity in both
      bacterial growth phases. Because the combination of flucloxacillin and gentamicin
      combines the inhibition of exotoxin production with high bactericidal activity at
      least in logarithmic-phase cultures, it should be considered an alternative to
      clindamycin for the treatment of exotoxin-mediated diseases, especially in
      patients with overwhelming infections.

PMID- 9257742
TI  - Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for
      structure-based inhibitor design: crystallization and inhibition studies with
      purine analogs.
AB  - The hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi is a
      potential target for enzyme structure-based inhibitor design, based on previous
      studies which indicate that these parasites lack the metabolic enzymes required
      for de novo synthesis of purine nucleotides. By using a bacterial complement
      selection system, 59 purine analogs were assayed for their interaction with the
      HPRTs from T. cruzi and Homo sapiens. Eight compounds were identified from the
      bacterial assay to have an affinity for the trypanosomal enzyme. Inhibition
      constants for four of these compounds against purified recombinant trypanosomal
      and human HPRTs were determined and compared. The results confirm that the
      recombinant system can be used to identify compounds which have affinity for the
      trypanosomal HPRT. Furthermore, the results provide evidence for the importance
      of chemical modifications at positions 6 and 8 of the purine ring in the binding
      of these compounds to the HPRTs. An accurate three-dimensional structure of the
      trypanosomal enzyme will greatly enhance our understanding of the interactions
      between HPRTs and these compounds. Toward this end, crystallization conditions
      for the trypanosomal HPRT and preliminary analysis of X-ray diffraction data to a
      resolution of 2 A is reported. These results represent significant progress
      toward a structure-based approach to the design of inhibitors of the HPRT of
      trypanosomes with the long-range goal of developing new drugs for the treatment
      of Chagas' disease.

PMID- 9257743
TI  - Postexposure factors influencing the duration of postantibiotic effect:
      significance of temperature, pH, cations, and oxygen tension.
AB  - The purpose of the present study was to assess and compare the impacts of various
      postexposure conditions on postantibiotic effect (PAE). PAEs were induced in
      Staphylococcus aureus and Escherichia coli by exposing the organisms to different
      antibiotics (penicillin G, ampicillin, erythromycin, ciprofloxacin, and
      gentamicin) at 5 or 10 times the MIC in plain Mueller-Hinton broth for 1 h at 35
      degrees C. Regrowth was determined by measuring the viable counts after drug
      removal by a 10(-3) or 10(-4) dilution procedure under various postexposure
      conditions (incubation temperatures at 20, 25, 30, or 35 degrees C; growth under
      shaken, unshaken, anaerobic conditions; pH 6.0, 7.4, or 9.0; and with sodium
      chloride concentrations at 0, 1, 3, or 6%). PAE increased in response to a
      decrease in incubation temperature from 35 to 20 degrees C, and a significant
      correlation between bacterial generation times and duration of PAEs (r2, 0.82 to
      0.97) was demonstrated. The duration of PAE was also modified by the pH in the
      regrowth medium. PAE increased considerably for S. aureus at pH 6.0 and 9.0
      compared to that at pH 7.4 after induction with penicillin G, and with gentamicin
      the PAE against S. aureus recovering at pH 6.0 also increased considerably. A
      high concentration of sodium chloride in the regrowth medium produced the most
      extensive changes in PAE except for that against E. coli induced by ampicillin.
      PAE increased significantly in response to increased salinity. No recovery even
      after overnight incubation was detected for S. aureus after preexposure to
      penicillin, ciprofloxacin, or gentamicin. Only minor changes in the duration of
      PAE were observed in relation to recovery oxygen tension. It is concluded that
      many postexposure factors have a profound effect on the duration of PAE.

PMID- 9257744
TI  - Enhancement of bismuth antibacterial activity with lipophilic thiol chelators.
AB  - The antibacterial properties of bismuth are greatly enhanced when bismuth is
      combined with certain lipophilic thiol compounds. Antibacterial activity was
      enhanced from 25- to 300-fold by the following seven different thiols, in order
      of decreasing synergy: 1,3-propanedithiol, dimercaprol (BAL), dithiothreitol, 3
      mercapto-2-butanol, beta-mercaptoethanol, 1-monothioglycerol, and
      mercaptoethylamine. The dithiols produced the greatest synergy with bismuth at
      optimum bismuth-thiol molar ratios of from 3:1 to 1:1. The monothiols were
      generally not as synergistic and required molar ratios of from 1:1 to 1:4 for
      optimum antibacterial activity. The most-active mono- or dithiols were also the
      most soluble in butanol. The intensity of the yellow formed by bismuth-thiol
      complexes reflected the degree of chelation and correlated with antibacterial
      potency at high molar ratios. The bismuth-BAL compound (BisBAL) was active
      against most bacteria, as assessed by broth dilution, agar diffusion, and agar
      dilution analyses. Staphylococci (MIC, 5 to 7 microM Bi3+) and Helicobacter
      pylori (MIC, 2.2 microM) were among the most sensitive bacteria. Gram-negative
      bacteria were sensitive (MIC, < 17 microM). Enterococci were relatively resistant
      (MIC, 63 microM Bi3+). The MIC range for anaerobes was 15 to 100 microM Bi3+,
      except for Clostridium difficile (MIC, 7.5 microM). Bactericidal activity
      averaged 29% above the MIC. Bactericidal activity increased with increasing pH
      and/or increasing temperature. Bismuth-thiol solubility, stability, and
      antibacterial activity depended on pH and the bismuth-thiol molar ratio. BisBAL
      was stable but ineffective against Escherichia coli at pH 4. Activity and
      instability (reactivity) increased with increasing alkalinity. BisBAL was acid
      soluble at a molar ratio of greater than 3:2 and alkaline soluble at a molar
      ratio of less than 2:3. In conclusion, certain lipophilic thiol compounds
      enhanced bismuth antibacterial activity against a broad spectrum of bacteria. The
      activity, solubility, and stability of BisBAL were strongly dependent on the pH,
      temperature, and molar ratio. Chelation of bismuth with certain thiol agents
      enhanced the solubility and lipophilicity of this cationic heavy metal, thereby
      significantly enhancing its potency and versatility as an antibacterial agent.

PMID- 9257745
TI  - Open randomized study of cefepime versus piperacillin-gentamicin for treatment of
      febrile neutropenic cancer patients.
AB  - An open-label randomized trial comparing the efficacy and safety of cefepime
      versus piperacillin plus gentamicin (P+G) given intravenously for the treatment
      of febrile episodes in neutropenic patients with underlying malignancy was
      conducted at two oncology centers. Over a 30-month period 111 patients were
      enrolled and 99 patients were found to be suitable for evaluation. At the 72-h
      time of evaluation, cefepime monotherapy and P+G combination therapy produced
      comparable clinical response rates (78% for both). P+G and cefepime produced
      comparable response rates in microbiologically documented (78 versus 71%),
      clinically documented (100 versus 100%), and possible (75 versus 79%) infections.
      The P+G and cefepime treatments achieved comparable microbiological eradication
      of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P
      = 0.37) organisms. There were no statistically significant differences in the
      rates of superinfection between the groups; however, more superinfections of
      fungal origin were noted in the P+G group. Cefepime was demonstrated to be an
      effective and safe treatment for febrile episodes in neutropenic patients with
      malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy.
      Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer
      patients.

PMID- 9257746
TI  - Clarithromycin lowers plasma zidovudine levels in persons with human
      immunodeficiency virus infection.
AB  - The use of antiretroviral agents and drugs for the treatment and prophylaxis of
      opportunistic infections has lengthened the survival of persons with AIDS. In the
      era of multidrug therapy, drug interactions are important considerations in
      designing effective and tolerable regimens. Clarithromycin has had a significant
      impact on the treatment of disseminated Mycobacterium avium complex infection,
      and zidovudine is the best-studied and one of the most widely used antiretroviral
      agents in this population. We conducted a study to determine the maximally
      tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and
      zidovudine individually and in combination. Mixing studies were conducted to
      simulate potential interaction in the gastric environment. The simultaneous
      administration of zidovudine and clarithromycin had little impact on the
      pharmacokinetics of clarithromycin or of its major metabolite. However,
      coadministration of zidovudine and clarithromycin at three doses (500 mg orally
      [p.o.] twice daily [b.i.d.], 1,000 mg p.o. b.i.d., and 2,000 mg p.o. b.i.d.)
      reduced the maximum concentration of zidovudine by 41% (P < 0.005) and the area
      under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05)
      and increased the time to maximum concentration of zidovudine by 84% (P < 0.05),
      compared with zidovudine administered alone. Mixing studies did not detect the
      formation of insoluble complexes due to chelation, suggesting that the decrease
      in zidovudine concentrations results from some other mechanism. Simultaneous
      administration of zidovudine and clarithromycin appears to decrease the levels of
      zidovudine in serum, and it may be advisable that these drugs not be given at the
      same time. Drug interactions should be carefully evaluated in persons with
      advanced human immunodeficiency virus infection who are receiving multiple
      pharmacologic agents.

PMID- 9257747
TI  - Inducible expression of human hepatitis B virus (HBV) in stably transfected
      hepatoblastoma cells: a novel system for screening potential inhibitors of HBV
      replication.
AB  - We report the development and isolation of a cell line, termed HepAD38, that
      replicates human hepatitis B virus (HBV) under conditions that can be regulated
      with tetracycline. In the presence of the antibiotic, this cell line is free of
      virus due to the repression of pregenomic (pg) RNA synthesis. Upon removal of
      tetracycline from the culture medium, the cells express viral pg RNA, accumulate
      subviral particles in the cytoplasm that contain DNA intermediates characteristic
      of viral replication, and secrete virus-like particles into the supernatant.
      Since the HepAD38 cell line can produce high levels of HBV DNA, it should be
      useful for analyses of the viral replication cycle that depend upon viral DNA
      synthesis in a synchronized fashion. In addition, this cell line has been
      formatted into a high-throughput, cell-based assay that permits the large-scale
      screening of diverse compound libraries for new classes of inhibitors of HBV
      replication.

PMID- 9257749
TI  - Influence of intravenously administered ciprofloxacin on aerobic intestinal
      microflora and fecal drug levels when administered simultaneously with
      sucralfate.
AB  - Ciprofloxacin, when given intravenously (i.v.), is secreted in significant
      amounts via the mucosa into the intestinal lumen. Sucralfate inhibits the
      antimicrobial activity of ciprofloxacin. The effect of combined therapy on the
      intestinal flora was investigated in 16 healthy volunteers. They were randomly
      assigned to two groups. Group A received 2 g of sucralfate orally three times a
      day for 7 days and 400 mg of ciprofloxacin i.v. twice a day (b.i.d.) starting 3
      days after the sucralfate administration began. Group B was given only 400 mg of
      ciprofloxacin i.v. b.i.d. for 4 days. A total of 9 stool samples were collected
      from each subject beginning the week before ciprofloxacin was administered and on
      days -1, 1, 2, 3, 4, 7, 9, and 10 or 11 after commencement of the infusion
      period. The aerobic fecal flora was determined by standard microbiological
      methods. Measurements of fecal ciprofloxacin levels were based on high
      performance liquid chromatography. Counts of bacteria of the family
      Enterobacteriaceae decreased in all subjects and were below 10(2) CFU/g in eight
      of eight subjects (group A) and six of eight subjects (group B) on day 4, but
      they returned to normal in all but one subject (group A) 10 days after the last
      infusion. The decreases in levels of bacteria of the family Enterobacteriaceae
      were not significantly different in groups A and B (Kaplan-Meier test).
      Staphylococci and nonfermenters responded variably, enterococci and lactobacilli
      remained unchanged, and candida levels increased transiently in four subjects
      (two in each group). Maximum fecal drug levels ranged from 251 to 811 microg/g.
      No significant difference could be found between the two groups. The i.v.
      application of ciprofloxacin eliminates intestinal bacteria of the family
      Enterobacteriaceae in a rapid and selective manner. This effect is not affected
      by simultaneous oral application of sucralfate.

PMID- 9257750
TI  - Activity of a new liposomal formulation of amphotericin B against two strains of
      Leishmania infantum in a murine model.
AB  - The efficacy of a new liposomal formulation of amphotericin B was compared to
      that of amphotericin B deoxycholate (Fungizone) in a murine model of visceral
      leishmaniasis induced by Leishmania infantum. Median effective doses (ED50) were
      determined with two different strains: strain 1 was obtained from an untreated
      patient, and strain 2 was obtained from a patient who had received 12.5 g of
      amphotericin B over 3 years. BALB/c mice were infected intravenously on day 0
      with promastigotes and then treated on days 14, 16, and 18 (strain 1) or on days
      21, 23, and 25 (strain 2) with the liposomal formulation of amphotericin B (five
      doses were tested for each strain: 0.05, 0.1, 0.5, 0.8, and 3 mg/kg of body
      weight) or with conventional amphotericin B (four doses were tested for each
      strain: 0.05, 0.1, 0.5, and 0.8 mg/kg). Mice in the control group received normal
      saline solution. The liposomal amphotericin B formulation was about three times
      more active than the conventional drug against both strains. ED50 of the
      liposomal formulation were 0.054 (strain 1) and 0.194 (strain 2) mg/kg. ED50 of
      conventional amphotericin B were 0.171 (strain 1) and 0.406 (strain 2) mg/kg.
      Determination of drug tissular levels, 3 days after the last drug administration,
      showed a drug accumulation in hepatic and splenic tissues much higher after
      administration of liposomal amphotericin B than after conventional amphotericin
      B. A lack of toxicity was noted in all groups treated with the liposomal
      formulation.

PMID- 9257748
TI  - Altered permeability and beta-lactam resistance in a mutant of Mycobacterium
      smegmatis.
AB  - Beta-lactam resistance in mycobacteria results from an interplay between the
      following: (i) beta-lactamase production, (ii) affinity of the penicillin-binding
      proteins (PBPs) for the drugs, and (iii) permeation of the drugs. A laboratory
      mutant of Mycobacterium smegmatis was studied in order to evaluate the roles of
      these factors in beta-lactam resistance. Mutant M13 was between 7- and 78-fold
      more resistant than the wild type to cephaloridine, cefoxitin, cefazolin,
      cefamandole, and cephalothin. Increased beta-lactamase activity toward these
      antibiotics was not observed in the mutant. The PBP profiles of the wild type and
      M13 were comparable. However, the affinities of PBP 1 for the beta-lactams tested
      were lower for the mutant than for the wild type. The permeation of the drugs
      measured in intact cells was lower for M13 than for the parent strain. The
      liposome swelling technique, which could be used for cephaloridine, also
      supported this view. Reduced permeation was not restricted to the beta-lactams
      alone. Glycine uptake was also lower in M13. Taken together, the results suggest
      that decreased affinities of PBP 1 for beta-lactams, combined with the decreased
      permeability of the cell wall of the mutant, lead to the development of high
      level acquired beta-lactam resistance.

PMID- 9257751
TI  - The postantibiotic effect of imipenem: relationship with drug concentration,
      duration of exposure, and MIC.
AB  - The postantibiotic effect (PAE) of imipenem against Escherichia coli was measured
      at a wide variety of drug concentrations and times of exposure. We observed that
      the area under the concentration-time curve of drug exposure (AUC), the product
      of time of exposure and concentration of drug, is a much better predictor of the
      duration of the PAE than either parameter alone. We also measured the PAE of
      imipenem against strains of gram-positive and gram-negative bacteria for which
      MICs varied widely. The E50, the AUC required to produce 50% of the maximum PAE,
      is correlated with the MIC and is independent of species. This may explain why
      the duration of the PAE differs for bacteria of the same species for which MICs
      are different.

PMID- 9257753
TI  - Pharmacokinetics of L-749,345, a long-acting carbapenem antibiotic, in primates.
AB  - L-749,345 is a carbapenem antibiotic, currently in phase II clinical trials,
      which possesses a broad antibacterial spectrum and extended half-life. The time
      courses of levels of the drugs in plasma and urinary recovery were evaluated for
      L-749,345, imipenem-cilastatin (IPM), and ceftriaxone (CTX) in male rhesus
      monkeys (Macaca mulatta) and a chimpanzee (Pan troglodytes). The chimpanzee
      pharmacokinetics was predictive of human results and indicated a compound that
      was superior to IPM and approached CTX in its ability to persist in the
      circulation. Levels of binding to protein, in the range of clinically relevant
      concentrations in serum, are virtually equivalent for L-749,345 and CTX in
      humans. Results of a crossover bioassay versus those of a high-pressure liquid
      chromatography assay of 1-g human samples showed that there were no bioactive
      metabolites of L-749,345. The extended half-life at elimination phase of L
      749,345 allows consideration of single daily dosing. In contrast to results with
      IPM, the improved stability of L-749,345 with respect to hydrolysis by the renal
      dehydropeptidase I (0.25 times the rate of IPM) results in urinary recovery
      sufficient for the drug's use as a single agent.

PMID- 9257752
TI  - Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo
      activity.
AB  - Protegrin-1 (PG-1) is a cysteine-rich, 18-residue beta-sheet peptide isolated
      from porcine leukocytes with antimicrobial activity against a broad range of
      microorganisms. The MICs of PG-1 against representative gram-positive and gram
      negative bacteria ranged from 0.12 to 2 microg/ml. At these levels, PG-1 was
      rapidly bactericidal in vitro, reducing the number of viable CFU of either
      methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa by
      more than three log units in less than 15 min. Resistance to PG-1 did not develop
      after 11 subculturings of P. aeruginosa or 18 subcultures of MRSA in Mueller
      Hinton broth containing PG-1 at one-half the MIC. Under similar conditions of
      serial passage, the MICs of norfloxacin and gentamicin against P. aeruginosa
      increased 10 and 190 times, respectively. Similarly, the MIC of norfloxacin
      against MRSA increased 85 times. Immunocompetent mice inoculated
      intraperitoneally (i.p.) with P. aeruginosa or S. aureus exhibited 93 to 100%
      mortality in the vehicle control group compared with 0 to 27% mortality in
      animals that received a single i.p. injection of PG-1 (0.5 mg/kg of body weight).
      Mice inoculated with S. aureus by intravenous (i.v.) injection and dosed 0 to 60
      min later with a single i.v. injection of PG-1 (5 mg/kg) had a mortality of 7 to
      33%, compared to a mortality of 73 to 93% in the vehicle controls. In leukopenic
      mice inoculated i.v. with vancomycin-resistant Enterococcus faecium, mortality
      was 87% in the vehicle control group and 33% in animals that received a single
      i.v. injection of PG-1 (2.5 mg/kg). Taken together, these data indicate that PG-1
      has potential for use as an antimicrobial agent in the treatment of local or
      systemic infections caused by clinically relevant pathogens.

PMID- 9257754
TI  - An extracellular factor regulating expression of the chromosomal aminoglycoside
      2'-N-acetyltransferase of Providencia stuartii.
AB  - The chromosomal aac(2')-Ia gene in Providencia stuartii encodes a housekeeping 2'
      N-acetyltransferase [AAC(2')-Ia] involved in the acetylation of peptidoglycan. In
      addition, the AAC(2')-Ia enzyme also acetylates and confers resistance to the
      clinically important aminoglycoside antibiotics gentamicin, tobramycin, and
      netilmicin. Expression of the aac(2')-Ia gene was found to be strongly influenced
      by cell density, with a sharp decrease in aac(2')-Ia mRNA accumulation as cells
      approached stationary phase. This decrease was mediated by the accumulation of an
      extracellular factor, designated AR (for acetyltransferase repressing)-factor. AR
      factor was produced in both minimal and rich media and acted in a manner that was
      strongly dose dependent. The activity of AR-factor was also pH dependent, with
      optimal activity at pH 8.0 and above. Biochemical characterization of conditioned
      media from P. stuartii has shown that AR-factor is between 500 and 1,000 Da in
      molecular size and is heat stable. In addition, AR-factor was inactivated by a
      variety of proteases, suggesting that it may be a small peptide.

PMID- 9257756
TI  - A study to determine the pharmacokinetics and inflammatory fluid penetration of
      two doses of a solid formulation of the hexetil prodrug of a trinem, sanfetrinem
      (GV 104326).
AB  - The trinem sanfetrinem (GV 104326) was administered as the oral hexetil prodrug
      GV 118819X in two dose levels to six healthy volunteers. A single dose equivalent
      to 125 mg of sanfetrinem was administered, followed 6 weeks later by a single
      dose equivalent to 500 mg of sanfetrinem. The concentrations of the drug in
      plasma, cantharidin-induced inflammatory fluid, and urine were measured with a
      microbiological assay. The stability of sanfetrinem was studied in serum and
      inflammatory fluid. The mean peak concentrations in plasma of 0.77 and 2.47
      microg/ml were attained at 1.1 and 2.0 h after the 125- and 500-mg doses,
      respectively. Mean peak concentrations in inflammatory exudate of 0.26 and 0.86
      microg/ml were attained at 2.80 and 2.67 h after the 125- and 500-mg doses,
      respectively. The mean terminal elimination half-lives in plasma were 1.33 and
      1.97 h for the 125- and 500-mg doses, respectively. The half-lives in the
      inflammatory fluid were 1.66 and 1.74 h for the 125- and 500-mg doses,
      respectively. The overall penetration of the drug into the inflammatory fluid was
      51.4 and 47.0% for the 125- and 500-mg doses, respectively. Mean urine recovery
      was greater following 500 mg (24.15%) than after 125 mg (18.4%) of sanfetrinem.
      Sanfetrinem was relatively unstable in the inflammatory exudate in vitro (half
      life, 5.5 h), and this could explain the poor penetration of the drug in the
      inflammatory exudate observed in this study.

PMID- 9257755
TI  - Inhibition of replication of hepatitis B virus by cytallene in vitro.
AB  - The acyclic cytosine nucleoside analog cytallene [1-(4'-hydroxy-1',2'
      butadienyl)cytosine], which has both (+)- and (-)-enantiomers, was evaluated for
      its anti-hepatitis B virus (HBV) activity in 2.2.15 cells and was found to have
      potent activity against HBV DNA synthesis. The R-(-)-enantiomer was found to be
      the more active of the cytallene enantiomers, with a 50% inhibition concentration
      against HBV synthesis (HBIC50) of 0.08 microM. Its antiviral activity could be
      reversed by deoxycytidine (dC) and less efficiently by cytidine. Upon removal of
      the R-(-)-enantiomer from culture medium, the synthesis of HBV DNA could
      reinitiate, which suggested that the antiviral action is reversible. The R-(-)
      enantiomer was also found to be more cytotoxic than the S-(+)-enantiomer. The
      degree of cytotoxicity varied among the cell lines, with a 50% inhibition of cell
      growth at greater than 10 microM. The R-(-)-enantiomer had no effect on HBV RNA
      synthesis and mitochondrial DNA synthesis at a concentration of 10 times or more
      than the HBIC50. The two enantiomers cannot be deaminated by dC deaminase, and
      they can be phosphorylated by cytoplasmic dC kinase. The R-(-)-enantiomer of
      cytallene is the first acyclic cytosine analog with potent inhibitory activity
      against HBV similar to those of other L-(-)-ddC analogs.

PMID- 9257757
TI  - Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus
      infected individuals receiving concomitant zidovudine.
AB  - This phase I, double-blind, randomized, placebo-controlled, parallel-design study
      was conducted to evaluate the safety and pharmacokinetics of levofloxacin in
      human immunodeficiency virus (HIV)-infected subjects concomitantly receiving a
      stable regimen of zidovudine (AZT). Sixteen HIV-infected males with CD4-cell
      counts ranging from 100 to 550 and not experiencing significant AZT intolerance
      were enrolled. Subjects received levofloxacin (350 mg of levofloxacin
      hemihydrate) or a placebo (eight subjects per treatment group) as a single oral
      dose on day 1, multiple doses every 8 h from days 3 to 9, and a single dose on
      day 10. On days 1 and 10, an AZT dose (100 mg) was administered concurrently with
      the study drug. In between these doses, AZT was administered according to the
      regimen used by the subject prior to entering the study up to a maximum of 500
      mg/day. Plasma levofloxacin concentrations were monitored for 36 h after
      levofloxacin dosing on day 1, immediately prior to the morning doses on days 3 to
      9, and for 72 h after dosing on day 10. Plasma AZT concentrations were monitored
      on day 0 for baseline (for 6 h after the AZT dose) and for 4 h after the AZT
      doses on days 1 and 10. Levofloxacin was rapidly absorbed (time to maximum plasma
      concentration, approximately 1.0 h) and extensively distributed in the body with
      an apparent volume of distribution of approximately 104 liters (approximately
      1.34 liters/kg). Steady-state conditions on day 10 were confirmed.
      Pharmacokinetic profiles of levofloxacin from single doses and multiple (three
      times-daily) doses were similar, with a moderate accumulation (observed day 10-to
      day 1 ratio of the maximum plasma concentration, approximately 185% versus
      expected 169%; for the corresponding ratio of the area under the concentration
      time curve from 0 to 8 h [AUC(0-8)], the values were observed 217% versus
      expected 169%) at steady state. Mean average steady-state peak plasma
      concentration, plasma levofloxacin concentration at the end of the dosing
      interval, AUC(0-8), terminal half-life, and total body clearance were 7.06
      microg/ml, 3.62 microg/ml, 37.4 microg x h/ml, 7.2 h, and 9.4 liters/h (0.12
      liters/h/kg), respectively. Pharmacokinetic profiles of levofloxacin in HIV
      infected patients did not appear to be affected by the concomitant administration
      of AZT; nor were AZT pharmacokinetics altered by levofloxacin. Oral
      administration of 350 mg of levofloxacin hemihydrate every 8 h appeared to be
      well tolerated by the subjects. There were no apparent differences in adverse
      events between the two treatment groups. There were no clinically significant
      changes from baseline in any laboratory parameter or vital sign following
      treatments observed in this study. The study results suggest that there is no
      need for levofloxacin dosage adjustment in HIV-seropositive subjects who
      concomitantly receive AZT.

PMID- 9257758
TI  - Cloning and sequencing of a novel gene (recG) that affects the quinolone
      susceptibility of Staphylococcus aureus.
AB  - In a study of the quinolone resistance genes in Staphylococcus aureus, a recG
      homolog was cloned as a gene affecting quinolone susceptibility. Sequencing
      analysis revealed that the gene consists of 2,061 nucleotides and encodes a 686
      amino-acid polypeptide, which shows 38, 39, and 50% amino acid identity with the
      RecGs of Escherichia coli, Haemophilus influenzae, and Streptococcus pneumoniae,
      respectively. Seven helicase motifs are well conserved in the gene product. A
      plasmid carrying the gene complemented a recG-deficient mutant of E. coli with
      respect to mitomycin hypersusceptibility, demonstrating that the gene product is
      functionally equivalent to E. coli RecG. These results indicate that the gene is
      the recG gene of S. aureus. S. aureus RCM101 (recG::Tn551), designated S. aureus
      3f33, is four to eight times more susceptible to quinolones than the parent
      strain, RCM101. The transformation of strain 3f33 with a plasmid carrying the S.
      aureus recG gene made it as quinolone resistant as strain RCM101. These results
      suggest that the recG gene is involved in the repair of DNA damage resulting from
      quinolone treatment in S. aureus.

PMID- 9257759
TI  - Treatment of murine disseminated candidiasis with L-743,872.
AB  - L-743,872 (M991), which is a pneumocandin derivative, was evaluated in a mouse
      model of disseminated candidiasis caused by a fluconazole-resistant isolate of
      Candida albicans. In immunocompetent mice M991 prolonged survival at doses as low
      as 0.0125 mg/kg of body weight per day. In neutropenic mice 0.05 mg/kg was the
      lowest effective dose. M991 is a very potent drug for treatment of disseminated
      candidiasis.

PMID- 9257760
TI  - Effect of tryptophan-N-formylated gramicidin on growth of Plasmodium berghei in
      mice.
AB  - The effect of tryptophan-N-formylated gramicidin (NFG) on the growth of
      Plasmodium berghei in mice was tested in three different experiments. NFG was
      shown to be capable of inhibiting the growth of the parasite in a dose-dependent
      way, although its action did not result in elimination of the parasite and was
      only temporary, preventing mice from early death, presumably due to cerebral
      malaria, but not from fatal generalized malaria. Intriguingly, a similar
      observation was made with two other drugs, (S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)adenine, an inhibitor of viral and eukaryotic DNA
      polymerases, and the presumed topoisomerase II inhibitor, a bisquaternary
      quinolinium salt. A rise in the level of parasitemia after 8 days, despite
      continued treatment, was not due to parasite-induced reticulocytosis, as
      demonstrated in experiments in which this condition was induced artificially. NFG
      was added in the form of lipid vesicles in which the peptide had been
      incorporated. The inhibitory action of NFG was not modulated by the lipid
      composition of the vesicles. Control experiments did not demonstrate any toxicity
      of NFG when it was administered in lipid vesicles. The main observation is that
      NFG is able to inhibit the growth of a malaria parasite in vivo at concentrations
      that are well tolerated by the host.

PMID- 9257761
TI  - Pharmacokinetics of intravenously and intramuscularly administered cefepime in
      infants and children.
AB  - The pharmacokinetic characteristics of cefepime were determined after first dose
      (n = 35) and again under steady-state conditions (n = 31) with a group of 37
      infants and children. In eight subjects, a cefepime dose given by intramuscular
      injection was substituted for an intravenous dose, and disposition
      characteristics were studied again. Study subjects ranged in age from 2.1 months
      to 16.4 years, and all had normal renal function. Each patient received 50 mg of
      cefepime/kg of body weight intravenously every 8 h, up to a total maximum
      individual dose of 2 g. With the exception of one study patient who received a
      single cefepime dose for surgical prophylaxis, the patients received cefepime for
      2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution,
      total body clearance, and renal clearance after first dose administration
      averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although
      cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6
      months of age than for older subjects, no differences in cefepime disposition
      characteristics between first dose and steady-state evaluations were observed.
      t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after
      intramuscular administration, reflecting the influence of absorption from the
      intramuscular injection site on cefepime elimination. Bioavailability after
      intramuscular administration averaged 82% (range, 61 to 124%). Fifty-seven
      percent of the first dose and 88.9% of the last dose were recovered as unchanged
      drug in urine over the 8- and 24-h sampling periods, respectively. These
      pharmacokinetic data support a single cefepime dosing strategy for patients > or
      =2 months of age. The integration of the cefepime pharmacokinetic data generated
      in our study with the MICs for important pathogens responsible for infections in
      infants and children supports the administration of a dose of 50 mg of
      cefepime/kg every 12 h for patients > or =2 months of age to treat infections
      caused by pathogens for which cefepime MICs are < or =8 mg/liter.

PMID- 9257763
TI  - Pharmacokinetics of isepamicin following a single administration by intravenous
      infusion or intramuscular injections.
AB  - The pharmacokinetics of isepamicin following administration of a 1-g dose were
      evaluated for 18 healthy male volunteers between the ages of 26 and 38. In a
      randomized crossover fashion, each volunteer received doses of isepamicin by a 30
      min intravenous infusion and as an intramuscular injection. Blood samples were
      collected at specified times after dosing and assayed for isepamicin by a
      validated radioimmunoassay method. The individual plasma concentration-time
      curves were analyzed by noncompartmental methods. In general, the
      pharmacokinetics after intravenous infusion and intramuscular injection were
      similar. As expected, the maximum concentration of isepamicin in serum following
      intramuscular injection (37.2 microg/ml) was lower than the observed
      concentration at the end of infusion (66.7 microg/ml). The areas under the
      concentration-time curves from 0 h to infinity following intramuscular and
      intravenous administration were 164.8 and 154.5 microg x hr/ml, respectively,
      indicating complete absorption following intramuscular administration. The
      respective mean terminal-phase half-life (t1/2) values were 2.6 and 3.6 h.
      Although t1/2 was slightly longer following intravenous infusion, the small
      difference in the observed t1/2 values was not considered to be clinically
      significant. Total body clearances following intramuscular injection and
      intravenous infusion were 1.3 and 1.4 ml/min/kg, respectively, which were similar
      to renal serum creatinine clearances in healthy volunteers (> 1.14 ml/min/kg).
      The drug was safe and well tolerated. The results of the present study clearly
      show complete absorption of isepamicin following intramuscular administration.
      The similarity in the pharmacokinetics after intravenous infusion and
      intramuscular dosing would permit interchangeable administration of isepamicin by
      either route without compromising clinical efficacy.

PMID- 9257762
TI  - Increased production of penicillin-binding protein 2, increased detection of
      other penicillin-binding proteins, and decreased coagulase activity associated
      with glycopeptide resistance in Staphylococcus aureus.
AB  - The mechanism of glycopeptide resistance in the genus Staphylococcus is unknown.
      Since these antimicrobial compounds act by binding the peptidoglycan precursor
      terminus, the target of transglycosylase and transpeptidase enzymes, it was
      hypothesized that resistance might be mediated in Staphylococcus aureus by
      increased production or activity of these enzymes, commonly called penicillin
      binding proteins (PBPs). To evaluate this possibility, glycopeptide-resistant
      mutants were prepared by passage of several clinical isolates of this species in
      nutrient broth containing successively increasing concentrations of the
      glycopeptide vancomycin or teicoplanin. Decreased coagulase activity and
      increased resistance to lysostaphin were uniformly present in the vancomycin
      resistant mutants. Peptidoglycan cross-linking increased in one resistant isolate
      and decreased in two resistant isolates. The amounts of radioactive penicillin
      that bound to each PBP in susceptible and resistant strains were compared; PBP2
      production was also evaluated by Western blotting. Increased penicillin labeling
      and production of PBP2 were found in all resistant derivatives selected by either
      vancomycin or teicoplanin. Moreover, the increase in PBP2 penicillin labeling
      occurred early in a series of vancomycin-selected derivatives and was strongly
      correlated (r > 0.9) with the increase in vancomycin and teicoplanin MIC. An
      increase in penicillin labeling also occurred, variably, in PBP1, PBP3, and/or
      PBP4. These data demonstrate a strong correlation between resistance to
      glycopeptides and increased PBP activity and/or production in S. aureus. Such an
      increase could allow PBPs to better compete with glycopeptides for the
      peptidoglycan precursor.

PMID- 9257764
TI  - Basis for the selective antibacterial activity in vitro of proton pump inhibitors
      against Helicobacter spp.
AB  - Proton pump inhibitors of the benzimidazole type exert a specific antibacterial
      activity against Helicobacter pylori in vitro. In the present study, the basis
      for this selectivity was investigated, and in particular, various factors
      affecting the in vitro antibacterial activity of sulfide analogs of
      benzimidazoles were studied. Upon preincubation of omeprazole for a period of up
      to 72 h in a buffer at pH 7, a product was formed that was bactericidal for H.
      pylori but had no effect on urease activity. Sulfide constitutes the main end
      product of degradation. The sulfide analog of omeprazole (H 168/22) exerted a
      bactericidal activity specifically against both resting (in buffer) and growing
      (in broth) Helicobacter spp., and time-kill in buffer at pH 5 was enhanced
      compared to that at pH 7. There was no or very low covalent binding of 3H-labeled
      H 168/22 to Helicobacter spp. or to other gram-negative and gram-positive
      bacteria. In the presence of fetal calf serum (FCS) under the same conditions,
      binding was only slightly lowered while the killing activity was markedly
      reduced, indicating a probably nonspecific interaction with proteins and/or
      protection of bacterial target(s) by FCS. Addition of H 168/22 (four times the
      minimum bactericidal concentration [MBC]) to exponentially growing H. pylori
      immediately stopped growth, and after an incubation period of 20 h viable counts
      were reduced by >7 log10. One-hour exposure of H. pylori to the drug followed by
      repeated washing retarded growth by about 2 h, indicating that the effect is
      reversible after short-term exposure. MICs and MBCs of various sulfide structures
      were lower than those obtained in broth after the addition of the corresponding
      sulfoxide. Thus, the MBC of the sulfide structure of omeprazole against 140
      clinical isolates of H. pylori ranged from 8 to 32 microg/ml, compared to an MBC
      of omeprazole of 32 to 128 microg/ml. A similar potency was also recorded against
      other helicobacters. In conclusion, formation of sulfides of benzimidazoles in
      culture media is the reason for the selective antibacterial effect against H.
      pylori. The sulfides rapidly exerted a reversible antibacterial activity, which
      was specific against both resting and growing Helicobacter spp. without any
      covalent protein binding.

PMID- 9257765
TI  - Circadian variation in urinary excretion of ciprofloxacin after a single-dose
      oral administration at 1000 and 2200 hours in human subjects.
AB  - Ciprofloxacin is routinely prescribed to treat a variety of infections, including
      those of the urinary tract. To achieve optimum therapeutic benefits of the drug,
      all of the factors which influence its pharmacokinetics and effectiveness need to
      be determined. This study investigated the urinary excretion kinetics of
      ciprofloxacin upon oral administration of a single dose of 250 mg at 1000 or 2200
      h in 12 healthy human subjects in a crossover design. The urine samples were
      analyzed for unchanged ciprofloxacin by a sensitive high-performance liquid
      chromatography method. A significant decrease in the rate and extent of
      ciprofloxacin excretion following 2200 h (109.59 versus 53.8 mg [P < 0.05])
      administration was observed. This result may be due to circadian changes in the
      factors affecting renal excretion and also probably metabolism of ciprofloxacin.

PMID- 9257766
TI  - Identification and characterization of IS1476, an insertion sequence-like element
      that disrupts VanY function in a vancomycin-resistant Enterococcus faecium
      strain.
AB  - The vanY gene of vancomycin-resistant enterococci encodes a D,D-carboxypeptidase.
      By using a PCR detection strategy, a VanA Enterococcus faecium clinical isolate
      was found to have an insertion sequence (IS)-like element designated IS1476 in
      vanY. The activity of the VanY D,D-carboxypeptidase in this isolate was decreased
      in a fluorometric fluoraldehyde o-phthalaldehyde assay with diacetyl-L-Lys-D-Ala
      D-Ala as the substrate. This, to our knowledge, is the first report of an IS-like
      element in a vancomycin resistance gene.

PMID- 9257767
TI  - Antibiotic exposure and its relationship to postantibiotic effect and
      bactericidal activity: constant versus exponentially decreasing tobramycin
      concentrations against Pseudomonas aeruginosa.
AB  - In vitro postantibiotic effects (PAEs) exhibited by a standard strain of
      Pseudomonas aeruginosa following exposure to tobramycin at constant
      concentrations were compared to those at exponentially decreasing concentrations.
      Exposure to a constant concentration showed more extensive bacterial killing and
      resulted in longer PAEs at comparable areas under the concentration-time curves
      above the MIC. This phenomenon suggests a significant contribution of
      pharmacokinetics to antimicrobial pharmacodynamics.

PMID- 9257769
TI  - Guinea pig model for Staphylococcus aureus native valve endocarditis.
AB  - We present a new experimental model of Staphylococcus aureus infective
      endocarditis in guinea pigs. Permanent aortic valve damage was produced by
      electrocoagulation after catheterization of the right carotid artery, which
      allowed avoidance of the intracardiac catheter to produce cardiac vegetations.
      Our model closely mimics pathological mechanisms of native valve endocarditis.

PMID- 9257768
TI  - In vitro activities of terbinafine in combination with fluconazole and
      itraconazole against isolates of Candida albicans with reduced susceptibility to
      azoles.
AB  - A checkerboard microdilution method was applied to study the in vitro interaction
      of terbinafine with either fluconazole and itraconazole against 30 strains of
      Candida albicans. Synergy was observed in 40% of the terbinafine-fluconazole
      interactions and in 43% of the terbinafine-itraconazole interactions, while
      antagonism was not observed. Even when only additivity was achieved, the
      combinations still showed beneficial effects since at least twofold reductions in
      the MICs of both drugs were found in 100% of the terbinafine-fluconazole
      interactions and in 76% of the terbinafine-itraconazole interactions.

PMID- 9257770
TI  - In vitro activity of Bay 12-8039, a new 8-methoxyquinolone.
AB  - MICs of Bay 12-8039 and comparative antimicrobials were determined for 820 recent
      clinical isolates. Ciprofloxacin was approximately 2-fold more active than Bay 12
      8039 and ofloxacin against Enterobacteriaceae and approximately 8-fold more
      active against Pseudomonas aeruginosa. Bay 12-8039 was approximately 2- to 16
      fold more active than ciproiloxacin and ofloxacin against nonfermenters (except
      P. aeruginosa), staphylococci, streptococci, enterococci, and anaerobes. As
      determined by regression analysis, there was a high degree of correlation among
      quinolone MICs.

PMID- 9257772
TI  - Comparative in vitro activities of carbapenem L-749,345 and other antimicrobials
      against multiresistant gram-negative clinical pathogens.
AB  - Carbapenems L-749,345 and imipenem had the lowest MICs at which 90% of isolates
      were inhibited (0.5 microg/ml) of 14 antimicrobial agents tested against 76
      multiresistant gram-negative clinical isolates with TEM- or SHV-type extended
      spectrum beta-lactamases and chromosomal or plasmid-determined AmpC beta
      lactamases, but the MIC of L-749,345 for one isolate of Klebsiella pneumoniae was
      16 microg/ml.

PMID- 9257771
TI  - Enhancement of nitric oxide synthesis by macrophages represents an additional
      mechanism of action for amphotericin B.
AB  - Amphotericin B (AmB) enhanced nitrite synthesis by murine macrophage-like J774.16
      cells in a dose-dependent fashion. This effect was retained in the presence of
      Cryptococcus neoformans capsular polysaccharide, a known virulence factor. AmB
      and anticapsular antibody increased nitrite synergistically. In all cases, AmB
      required gamma interferon; C. neoformans cells were unable to elicit nitrite,
      with or without AmB.

PMID- 9257773
TI  - In vitro evaluation of voriconazole against some clinically important fungi.
AB  - Voriconazole was compared to amphotericin B, fluconazole, and itraconazole by
      using an in vitro macrobroth dilution test based upon current National Committee
      for Clinical Laboratory Standards tentative standards against the dimorphic fungi
      and several opportunistic molds and yeasts. In all instances, the voriconazole
      MICs were lower than those of fluconazole. In most instances, the MICs were lower
      than the recorded MICs of amphotericin B and itraconazole.

PMID- 9257774
TI  - In vitro antifungal activity of pneumocandin L-743,872 against a variety of
      clinically important molds.
AB  - The in vitro activity of the new antifungal drug pneumocandin L-743,872 against
      55 isolates of clinically important molds was examined by an adapted macrobroth
      dilution method for yeasts. Pneumocandin L-743,872 exhibited in vitro antifungal
      activity against Alternaria sp., Aspergillus flavus, Aspergillus fumigatus,
      Curvularia lunata, Exophiala jeanselmei, Fonsecaea pedrosoi, Paecilomyces
      variotii, and Scedosporium apiospermum. The drug appeared to lack significant in
      vitro inhibitory activity against Fusarium oxysporum, Fusarium solani, Rhizopus
      arrhizus, Paecilomyces lilacinus, and Scedosporium prolificans.

PMID- 9257775
TI  - Evaluation of growth promotion and inhibition from mycobactins and
      nonmycobacterial siderophores (Desferrioxamine and FR160) in Mycobacterium aurum.
AB  - Heterologous mycobactins and the synthetic FR160 [N4-nonyl,N1,N8-bis(2,3
      dihydroxybenzoyl) spermidine hydrobromide (C3 0H4 6N3, O6 Br)] promoted growth in
      Mycobacterium aurum in low concentrations. They were otherwise highly inhibitory,
      as opposed to homologous mycobactin, which was strictly growth promoting.
      Desferrioxamine B (Desferal) had no significant effect on growth.

PMID- 9257776
TI  - Voriconazole (UK-109,496) inhibits the growth and alters the morphology of
      fluconazole-susceptible and -resistant Candida species.
AB  - The effects of voriconazole on the growth, ultrastructure, and leakage of
      cytoplasmic materials of Candida species were investigated. MIC data showed that
      voriconazole was more active than fluconazole. Exposure of yeast to voriconazole
      caused growth inhibition, cell wall thinning, and cell membrane degradation.
      Neither cell collapse nor release of cytoplasmic materials was observed in the
      treated cells.

PMID- 9257777
TI  - Comparison of single-dose oral grepafloxacin with cefixime for treatment of
      uncomplicated gonorrhea in men. The STD Study Group.
AB  - In a randomized open study, 351 male patients with uncomplicated gonorrhea were
      given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the
      299 microbiologically evaluable patients, urethral infections were cured in 99%
      (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given
      cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of
      participants who were infected with penicillin-resistant Neisseria gonorrhoeae
      and 97% in the 21% (62 of 299) of participants infected with tetracycline
      resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for
      treatment of uncomplicated gonorrhea in males.

PMID- 9257778
TI  - Fanconi syndrome associated with cidofovir therapy.

PMID- 9257779
TI  - TH1 and TH2 CD4+ cells in human allergic diseases.

PMID- 9257780
TI  - New directions in food allergy research.

PMID- 9257781
TI  - Hymenoptera sting anaphylaxis and urticaria pigmentosa: clinical findings and
      results of venom immunotherapy in ten patients.
AB  - BACKGROUND: Occasional patients with urticaria pigmentosa and anaphylaxis after
      Hymenoptera stings have been described. In this situation the question arises: Is
      anaphylaxis IgE-mediated or induced by pharmacologic mediator release from mast
      cells? METHODS: We investigated 10 patients with histologically confirmed
      urticaria pigmentosa and a history of anaphylaxis after honeybee or Vespula
      stings before and during immunotherapy with the respective venom. RESULTS: In
      eight of 10 patients, an elevated serum tryptase level was found. In two of 10
      patients, no venom-specific IgE could be detected by either skin tests or RAST.
      Five patients had no detectable venom-specific serum IgE, and in the remaining
      patients the level was low (<1 Phadebas RAST unit). Venom immunotherapy was well
      tolerated and caused only one mild systemic reaction in a patient during the dose
      increase phase. Six patients were re-stung while receiving venom immunotherapy:
      only one had a mild systemic reaction (angioedema) after a Vespula sting.
      CONCLUSION: Anaphylactic symptoms after Hymenoptera stings in patients with
      urticaria pigmentosa are most often IgE-mediated but can occasionally be observed
      in the absence of IgE sensitization to venom allergens. Venom immunotherapy can
      be safely and successfully used in patients with urticaria pigmentosa and sting
      anaphylaxis.

PMID- 9257782
TI  - Development and validation of a rhinoconjunctivitis and asthma symptom score for
      use as an outcome measure in clinical trials.
AB  - BACKGROUND: The measurement of health outcomes has become a priority for
      assessing and containing health care costs. OBJECTIVE: To develop and fully
      validate a simple symptom scale assessing both asthma and rhinoconjunctivitis,
      two interdependent conditions. METHODS: A self-administered questionnaire of 31
      items was tested in 102 patients with asthma and rhinoconjunctivitis between
      September 1992 and December 1994. The items were rated on a six-point Likert
      scale ranging from none to extremely severe and included commonly recorded
      symptoms of inflammation such as irritation, congestion, and discharge in the
      skin, eyes, nose, sinus, pharynx, and chest. RESULTS: Validation included (1)
      responsiveness: scores for 18 patients evaluated during an emergency room visit
      were statistically significantly different from those recorded after recovery and
      in a control group of 24 patients with asthma; (2) reliability: external
      consistency was 0.8 at 1 week, and internal consistency was 0.8 for individual
      organs and 0.7 for individual symptoms; (3) validity: a five-point scale better
      captured the distribution of values; irrelevant and redundant items were
      eliminated. The optimal questionnaire included 21 items. CONCLUSIONS: The symptom
      score was applicable, responsive, reliable, and valid. Used with existing
      validated tools such as treatment needs and quality of life assessment, it may
      provide a comprehensive picture of allergic airway disease for quality assurance
      or research purposes.

PMID- 9257783
TI  - Short-term immunotherapy: a prospective, randomized, double-blind, placebo
      controlled multicenter study of molecular standardized grass and rye allergens in
      patients with grass pollen-induced allergic rhinitis.
AB  - BACKGROUND: Short-term immunotherapy (STI) can be beneficial for patients who are
      noncompliant with long-term specific immunotherapy. OBJECTIVE: The efficacy and
      tolerance of STI with seven preseasonal injections of molecular standardized
      allergens from grass and rye pollen has been investigated in a double-blind,
      placebo-controlled multicenter study with 87 patients at 12 German University
      hospitals. METHODS: Symptoms of the eyes, nose, and bronchi and use of
      symptomatic drugs were documented daily in diaries by patients with allergic
      rhinitis to grass and/or rye pollen and without bronchial asthma. Patients were
      monitored by skin prick test titration and measurement of levels of specific IgE
      and IgG4. RESULTS: The median nasal score for the 10 weeks with the strongest
      symptoms during the grass pollen season was significantly lower (p = 0.014) with
      35.0 for STI (n = 41) versus 69.0 for placebo (n = 40); the overall symptom score
      was 54.0 for STI versus 97.5 for placebo (p = 0.020). Only STI-treated patients
      exposed to less than 40 pollen grains per cubic meter per week showed a
      significantly lower nasal symptom score of 39.0 versus 75.0 for placebo (p =
      0.006); these patients also had fewer nasal symptoms and less use of topical
      nasal drugs (p < 0.001). The threshold dose in skin prick tests was significantly
      higher, being 9.06 histamine equivalent for skin prick test (HEP) for STI-treated
      patients who received the maximum dose (n = 22) versus 4.33 HEP for placebo (p =
      0.005). Specific IgE levels were significantly higher, being 55.9 SU/ml for STI
      versus 39.2 SU/ml for placebo after seven injections (p = 0.006) and level of
      specific IgG4 was 5.36% for STI versus 1.28% for placebo (p < 0.001). No severe
      systemic reactions were observed. CONCLUSION: STI with seven preseasonal
      injections with molecular standardized allergens is effective and well tolerated.

PMID- 9257784
TI  - Oral immunotherapy with short ragweed extract in a novel encapsulated
      preparation: a double-blind study.
AB  - BACKGROUND: In the past, oral immunotherapy with allergens has had limited
      clinical effectiveness, presumably because of gastrointestinal destruction of
      allergens. OBJECTIVE: We have developed a new technique for microencapsulating
      protein antigens that permits them, when given orally, to bypass the stomach and
      be delivered to the small intestine in a highly immunogenic form. This study's
      purpose was to confirm the immunologic potency of orally administered short
      ragweed pollen extracts (SRW) microencapsulated (mSRW) by this new technique and
      to study the effectiveness of mSRW in controlling the symptoms of ragweed-induced
      hay fever. METHODS: Twenty-one SRW-sensitive patients were treated with mSRW in a
      double-blind placebo-controlled study. Serum SRW IgG and IgE antibodies and nasal
      secretory IgA antibodies were determined. During the ragweed season, symptoms
      were quantified by symptom-medication scoring. RESULTS: The treated patients had
      high titers of serum SRW IgG antibodies (1.15 microg/ml at baseline, increasing
      to 21.21 microg/ml), experienced regulation of the seasonal increase in serum SRW
      IgE antibodies (+9% vs +59% in placebo-treated patients), and produced a small
      amount of nasal SRW IgA antibodies. Despite an insubstantial pollen count, the
      symptom-medication scores in the treated group were lower than those in the
      placebo group (4.28 vs 6.18, p = 0.059), but the differences were statistically
      significant only in the subgroup that tolerated high doses (>20 microg of Amb a 1
      in 19 of 21 patients, p = 0.04). These effects were accomplished without inducing
      any systemic reactions with a dose of mSRW (mean, 23.8 microg of Amb a 1) only
      slightly higher than that used in high-dose subcutaneous immunotherapy.
      CONCLUSION: Oral mSRW seems a safe, easily administered, and immunologically
      potent treatment for ragweed-induced hay fever, but its ultimate utility requires
      further study.

PMID- 9257785
TI  - Increased theophylline metabolism in the menstrual phase of healthy women.
AB  - BACKGROUND: We previously reported on a Japanese woman with premenstrual asthma
      whose serum theophylline concentration was lower before the onset of her
      menstrual period. We evaluated the clearance of theophylline in each phase of her
      menstrual cycle and found an increase in clearance in the premenstrual and
      menstrual phases. OBJECTIVE: This study was designed to investigate whether
      changes in theophylline clearance may occur with the menstrual cycle in
      nonasthmatic women. METHODS: Aminophylline, 250 mg, was infused intravenously for
      45 minutes, and the clearance of theophylline was calculated in seven healthy,
      ovulatory women on days 1 or 2, 10, and 20 or 25 of the menstrual cycle. The
      serum concentration of theophylline was determined with an enzyme immunoassay
      (homogeneous). RESULTS: Theophylline clearance was significantly higher and its
      half-life was significantly shorter in the menstrual phase than in the follicular
      phase. CONCLUSION: The metabolism of theophylline, and consequently, its
      clearance were increased in healthy women around the onset of menses. Clinicians
      must therefore consider the menstrual variation in theophylline metabolism when
      prescribing this drug to female patients.

PMID- 9257786
TI  - Inflammation of small airways in asthma.
AB  - This study was designed to examine the inflammatory process in the central and
      peripheral airways of surgically resected lungs from asthmatic and nonasthmatic
      subjects. Lung specimens were inflated with cryoprotective, rapidly frozen, and
      systematically sampled. Cryosections prepared from frozen tissue blocks were
      fixed in acetone/methanol and immunostained with monoclonal antibodies by using
      the alkaline phosphatase-anti-alkaline phosphatase technique to detect CD3 (T
      cells), major basic protein (total eosinophils), EG2 (activated eosinophils),
      anti-tryptase (mast cells), anti-elastase (neutrophils), and CD68 (macrophages).
      All airways from patients with asthma demonstrated a significant increase in the
      numbers of T cells and total and activated eosinophils compared with airways from
      nonasthmatic subjects (p < 0.001). In the patients with asthma, the numbers of
      activated eosinophils but not T cells were significantly greater in airways with
      an internal perimeter less than 2 mm compared with those with an internal
      perimeter greater than 2 mm (p < 0.05). There were also significantly higher
      numbers of major basic protein-positive eosinophils, when expressed as a fraction
      of the alveolar wall tissue, in patients with asthma compared with control
      subjects (p < 0.05). In asthmatic airways with an internal perimeter of more than
      2 mm, there was a greater number of activated eosinophils in the tissue between
      the epithelium and the smooth muscle compared with the tissue between the smooth
      muscle layer and lung parenchyma (p < 0.05). In contrast, there was a greater
      number of total eosinophils in the outer airway layer compared with the inner
      airway layer (p < 0.05). These results show that there is a similar but more
      severe inflammatory process present in the peripheral compared with the central
      airways of patients with asthma, which is consistent with the fact that the
      smaller airways are a major site of obstruction in asthma.

PMID- 9257787
TI  - Damage of the pharyngeal mucosa and hyperresponsiveness of airway in sinusitis.
AB  - BACKGROUND: In sinusitis bronchoconstriction is supposed to originate from
      pharyngobronchial reflexes triggered by seeding of the inflammatory process into
      the pharynx. OBJECTIVE: Our aim was to evaluate whether in sinusitis bronchial
      and extrathoracic airway (EA) dysfunction correlate with morphologic
      abnormalities of the pharyngeal mucosa. METHODS: We performed histamine
      inhalation challenge, nasal lavage, and nasopharyngeal biopsies in 24
      nonasthmatic patients with exacerbation of chronic sinusitis. The histamine PC20
      was the threshold of bronchial responsiveness, and that causing 25% fall in
      maximal midinspiratory flow was the threshold of EA responsiveness (PC25MIF50).
      Thresholds of 8 mg/ml or less were assumed to indicate bronchial
      hyperresponsiveness (BHR) or EA hyperresponsiveness (EAHR). PC20 and PC25MIF50
      values were related to clinical data, nasal lavage fluid eosinophils, pharyngeal
      epithelium and basement membrane thickness, and density of submucosal vessels and
      nervous fibers. RESULTS: The PC20 was closely related to PC25MIF50 (p = 0.0004).
      Ten patients had EAHR, 9 had combined EAHR and BHR, and 5 had neither EAHR nor
      BHR. EAHR was strongly associated with epithelial thinning, and BHR with long
      standing sinusitis, a lower PC25MIF50, increased submucosal nerve density and
      increased nasal lavage fluid eosinophils. CONCLUSIONS: Our findings suggest that
      in nonasthmatic patients with sinusitis, pharyngeal damage may contribute to
      airway dysfunction by favoring the access of irritants to submucosal nerve
      endings, with activation of constrictive reflexes to the EA. Proliferation of
      sensory neurons, consequent to long-lasting pharyngeal inflammation, may cause
      more severe EA narrowing and activate pharyngobronchial reflexes.

PMID- 9257788
TI  - Eosinophils, mast cells, and basophils in induced sputum from patients with
      seasonal allergic rhinitis and perennial asthma: relationship to methacholine
      responsiveness.
AB  - OBJECTIVES: We attempted to determine whether inflammation is present in induced
      sputum of patients with seasonal allergic rhinitis (AR) as compared with those
      with perennial asthma (AS) and examined its relationship with bronchial
      responsiveness to methacholine. METHODS: Sputum was induced in 30 patients with
      seasonal rhinitis in response to grass pollens only and in 15 patients with
      stable, asymptomatic asthma. The AR group was divided according to methacholine
      PD20 value: the AR- group (n = 15) had a methacholine PD20 greater than 24
      micromol; the AR+ group (n = 15) had a methacholine PD20 ranging between 2.2 and
      19.6 micromol. In the AS group, methacholine PD20 ranged between 0.42 and 2.6
      micromol. The percentage of eosinophils and metachromatic cells (alcian blue
      positive) was assessed in sputum by light microscopy. Tryptase-positive cells and
      EG2+ cells were identified by immunocytochemistry with the mouse anti-human mast
      cell-tryptase monoclonal antibody and the monoclonal anti-eosinophil cationic
      protein antibody. RESULTS: We found that the number of eosinophils in the AS
      group was greater than that in the AR+ group (p < 0.05) and in the AR- group (p <
      0.01). Moreover, the eosinophil count was lower in the AR- group compared with
      the AR+ group (p < 0.05). Similarly, the number of EG2+ cells was greater in the
      AS group than in the AR group (p < 0.02) and the AR- group (p < 0.05). Moreover,
      the EG2+ cell count was lower in the AR- group than in the AR+ group (p < 0.05).
      The number of mast cells and basophils in the AS group was greater than that in
      the AR group (p < 0.05 and p < 0.01, respectively). Mast cells in sputum were
      tryptase-positive. Basophils were present in sputum from 23% of patients with AR
      and 53% of patients with asthma. There was a significant correlation between
      methacholine PD20 and eosinophils (p < 0.005) and mast cells (p < 0.02) but not
      with basophils in those patients showing a measurable methacholine PD20 (AR+ and
      AS groups). CONCLUSIONS: Inflammatory cells are present not only in the airways
      of patients with asthma but also in airways of patients with seasonal AR, even
      outside natural exposure. Moreover, we provide evidence for the presence of
      basophils in sputum of patients with asthma even during clinical remission. The
      presence of bronchial responsiveness is associated with an increase in the number
      of eosinophils and metachromatic cells. Our findings are consistent with the
      hypothesis that eosinophils, as well as mast cells, contribute to bronchial
      responsiveness not only in AS but also in seasonal AR.

PMID- 9257789
TI  - Evaluation of single-dose inhaled corticosteroid activity with an allergen
      challenge model.
AB  - BACKGROUND: Inhaled corticosteroids are the most commonly used antiinflammatory
      agents for asthma. There is no simple way to compare objectively the relative
      potency of inhaled corticosteroids. The allergen-induced late asthmatic response
      (LAR) can be suppressed by a single dose of inhaled corticosteroid. OBJECTIVE:
      This study was undertaken to evaluate LAR as a model for the determination of the
      relative potency of single doses of inhaled corticosteroids. METHODS: We compared
      doses of 200 and 800 microg of a highly active inhaled corticosteroid
      (budesonide) with placebo and a marginally active investigational inhaled
      corticosteroid (D5159). Ten atopic patients with asthma completed a randomized,
      double-blind, double-dummy, multicenter, four-way, crossover trial. A
      standardized allergen challenge with the identical dose of allergen was performed
      10 minutes after each of four blinded, single-dose treatments: 200 microg of
      budesonide, 800 microg of budesonide, 8 mg of D5159, and placebo, all
      administered from Turbuhaler. The LAR was recorded as the maximum percent fall in
      FEV1 between 4 and 7 hours, and the allergen-induced increase in methacholine
      airway responsiveness at 24 hours was recorded as the A log PC20 from the day
      before to the day after allergen challenge. RESULTS: There were no significant
      differences in the early asthmatic responses during the 4 days; the mean maximum
      percent in FEV1 fall ranged between 19.5% and 22%. D5159 produced a slight
      inhibition of the LAR with maximum percent fall in FEV1 recorded as 28.8% +/-
      5.0% for D5159 versus 34.1% +/- 4.8% for placebo (p < 0.05). There was a greater
      reduction recorded after administration of the two doses of budesonide. The mean
      LAR was 15.1% +/- 3.8% for 200 microg of budesonide and 11.2% +/- 2.3% for 800
      microg of budesonide (p < 0.01 compared with placebo and D5159). The two doses of
      budesonide were not statistically different. Airway responsiveness to
      methacholine increased by 1.07 doubling doses 24 hours after allergen challenge.
      This increased airway responsiveness was slightly, but not significantly, reduced
      by the three active treatments (0.6 to 0.91 doubling doses). CONCLUSION: The
      allergen-induced LAR model was able to differentiate a single dose of an active
      inhaled corticosteroid from placebo and a highly potent inhaled corticosteroid
      from a weak inhaled corticosteroid. The model did not differentiate between 2
      fourfold doses of the highly active inhaled corticosteroid (at the doses used in
      this study), neither for the fall in FEV1 nor for the increase in airway
      hyperresponsiveness.

PMID- 9257790
TI  - Protective effect of inhaled lysine acetylsalicylate on allergen-induced early
      and late asthmatic reactions.
AB  - Conflicting results have been reported on the effect of non-steroidal
      antiinflammatory drugs on allergen-induced asthmatic responses. The aim of this
      study was to investigate the effect of inhaled lysine acetylsalicylate (LASA) on
      the early and late allergen-induced responses. We studied 16 patients with mild,
      stable asthma who had an early asthmatic response and 10 patients with a dual
      (early and late) response. Each patient underwent two challenges with a single
      dose of allergen assessed in a preliminary test, after inhalation of either 720
      mg of LASA in 4 ml of saline solution or placebo, according to a randomized,
      double-blind protocol. Allergen-induced hyperreactivity to methacholine was
      measured in six patients from each of the early and the dual response groups 2
      hours and 24 hours after the challenge, respectively. In the patients with early
      response, the maximum fall in FEV1 after challenge was 24% +/- 1% after
      inhalation of placebo and 14% +/- 2% after inhalation of LASA (p < 0.005). No
      protection was observed in four patients who received the drug orally instead of
      by inhalation. In the patients with a dual response, the maximum FEV1 decrease
      during the early response was 27% +/- 2% after placebo and 21% +/- 2% after LASA
      (p < 0.025). During the late response (between 3 and 8 hours), the maximum
      decrease in FEV1 was 28% +/- 4% after placebo and 16% +/- 4% after LASA (p <
      0.005). In both groups allergen challenge caused a significant reduction in
      methacholine PD20 after treatment with placebo but not with LASA. Without
      allergen challenge, LASA had no effect on methacoline reactivity. We conclude
      that inhaled LASA significantly reduces both the early and the late asthmatic
      response to allergen challenge and that it prevents the allergen-induced airway
      hyperresponsiveness that follows these responses.

PMID- 9257791
TI  - Enhanced expression of high-affinity IgE receptor (Fc epsilon RI) alpha chain in
      human allergen-induced rhinitis with co-localization to mast cells, macrophages,
      eosinophils, and dendritic cells.
AB  - BACKGROUND: IgE-dependent activation of mast cells and basophils through the high
      affinity IgE receptor (Fc epsilon RI) is involved in the pathogenesis of allergen
      induced immediate and late responses. OBJECTIVE: We investigated the expression
      and cellular distribution of Fc epsilon RI in the nasal mucosa after allergen
      challenge in patients with summer hay fever. METHODS: Fourteen grass pollen
      sensitive patients and seven normal control subjects underwent nasal challenge
      with grass pollen and allergen diluent in random order separated by 2 weeks.
      Nasal airway caliber was monitored by acoustic rhinometry, and nasal biopsy was
      performed at 6 hours. Messenger RNA for Fc epsilon RI was determined by using
      reverse-transcription polymerase chain reaction, and Fc epsilon RI protein
      expression was determined by immunohistology with a mouse monoclonal antibody
      (22E7) and a rabbit polyclonal antibody (997) directed against the alpha subunit.
      Co-localization of Fc epsilon RI receptors was performed by using double
      immunostaining methods. RESULTS: In atopic subjects, there was a significant
      early decrease in nasal airway caliber, which extended up to 6 hours after
      allergen challenge. Fc epsilon RI mRNA levels were elevated at 6 hours (p =
      0.03). Cells expressing Fc epsilon RI protein were increased in patients with
      atopic rhinitis compared with normal control subjects (p = 0.03). Further
      increases in Fc epsilon RI+ cells were observed after allergen challenge only in
      the atopic group (p = 0.02). Double immunohistochemistry revealed that the
      majority of Fc epsilon RI+ cells were mast cells (64%), followed by macrophages
      (20%), eosinophils (4%), and dendritic cells (2%), with 10% Fc epsilon RI+ cells
      being unidentified. CONCLUSIONS: Our results demonstrate increased Fc epsilon RI
      expression during allergen-induced rhinitis and highlight a potential target for
      treatment.

PMID- 9257792
TI  - Heterogeneity of polyclonal IgE characterized by differential charge, affinity to
      protein A, and antigenicity.
AB  - Functional and physical heterogeneity of polyclonal IgE has been reported.
      Extremely low serum concentrations of IgE have limited the study of these
      important differences. We have purified polyclonal dog IgE and developed
      polyclonal and monoclonal (mAb C2) anti-dog IgE antibodies. In this study
      chromatofocusing of dog IgE revealed two biologically active IgE fractions: IgE1
      eluted at pH 5.0, and IgE2 eluted at pH 4.7. The two IgE subforms (IgEs)
      exhibited typical IgE characteristics: positive in the 48-hour passive cutaneous
      anaphylaxis response, heat-labile, identical molecular weight, and reactive to
      polyclonal anti-dog IgE. However, the two IgEs were found to be significantly
      heterogeneous. IgE1 bound to protein A and did not react with mAb C2 in ELISA and
      isoelectric focusing-immunoblotting, whereas IgE2 did not bind to protein A and
      reacted with mAb C2. Further, in sodium dodecylsulfate-polyacrylamide gel
      electrophoresis and immunoblotting, IgE2, but not IgE1, reacted with seven well
      defined mAb anti-human IgE antibodies and an mAb anti-mouse IgE antibody, even
      though both IgE1 and IgE2 reacted with polyclonal anti-human and anti-mouse IgE.
      Neuraminidase or endoglycosidase treatment did not abolish the differential
      antigenicity and charge of IgE1 and IgE2, although the antigenicity of IgE2 was
      significantly reduced after incubation with endoglycosidase. These data suggest
      that carbohydrate moieties are not involved in the observed differences in
      antigenicity and charge and that the two IgE molecules represent distinct
      isotypes. In studies with seven purified IgE fractions obtained from different
      ragweed-allergic dogs, the distribution of ragweed IgE2 varied 200-fold, whereas
      ragweed total IgE levels varied only fourfold. This raises the possibility of a
      relationship between different IgEs and the allergic response.

PMID- 9257793
TI  - Modulation of T-cell response to phospholipase A2 and phospholipase A2-derived
      peptides by conventional bee venom immunotherapy.
AB  - BACKGROUND: Immunologic mechanisms of desensitization are still incompletely
      understood. Safer methods of immunotherapy with reduced risks of anaphylaxis need
      to be developed. OBJECTIVE: To study the effects of conventional venom
      immunotherapy (VIT) on phospholipase A2(PLA2)-specific T cells and on T-cell
      reactivity to short and long synthetic peptides that map the PLA2 molecule.
      METHOD: Proliferation of a CD4+ cell-enriched peripheral blood mononuclear cell
      fraction and cytokine secretion by T cell lines from patients hypersensitive to
      bee venom and undergoing VIT in response to PLA2 and PLA2 synthetic peptides were
      measured. RESULTS: T-cell proliferation in response to three synthetic peptides,
      40 to 60 amino acids long and mapping the entire PLA2 molecule with an overlap of
      10 residues (1 to 59, 51 to 99, and 90 to 134) steadily increased during the
      first 14 weeks of VIT corresponding to the treatment period with incremental
      doses of antigen. These results are in contrast to the low proliferation indices
      obtained with short (15 amino acid-long) peptides, and the inability to
      characterize the immunodominant region of the molecule with short peptides. At
      the end of VIT (after 3 to 5 years), there was correspondingly, a marked decrease
      in T cell responsiveness to PLA2 and to its long synthetic peptides. This
      response was paralleled by a shift in the pattern of cytokine secretion by T cell
      lines from a T(H0)-type to a T(H1)-type pattern. CONCLUSION: After a transient
      increase in T-cell proliferation, late VIT was characterized by T-cell
      hyporesponsiveness to allergen and by modulation of cytokine secretion from a
      T(H0)-type to a T(H1)-type pattern. Because of their capacity to recruit multiple
      T-cell epitopes, long peptides mapping the entire PLA2 molecule appear to be
      efficient T cell stimulators and may represent potential candidates for peptide
      immunotherapy.

PMID- 9257794
TI  - Cytokine levels and inflammatory responses in developing late-phase allergic
      reactions in the skin.
AB  - BACKGROUND: Cytokines could play roles in the attraction of leukocytes into sites
      of IgE-mediated late-phase reactions (LPR) or in the activation of such cells at
      the sites. Previous studies found increased release of IL-6, IL-1, and
      granulocyte-macrophage colony-stimulating factor into skin chambers overlying
      allergen-challenged sites, mainly after 6 hours when LPR are already well
      developed. OBJECTIVE: To compare levels of several cytokines with inflammatory
      responses in skin chambers overlying developing LPRs. METHODS: Skin chambers were
      appended to denuded blister bases in 15 sensitive subjects, then challenged over
      a 5-hour period with pollen allergens (Ag) or buffer control (B). Levels of
      several chemotactic cytokines, eosinophil cationic product (released from
      eosinophils), and lactoferrin (released from neutrophils) were measured and
      leukocyte accumulation was assessed. RESULTS: Levels of the chemokines IL-8,
      RANTES, and monocyte chemotactic protein-1 (but not IL-1, IL-6, or granulocyte
      macrophage colony-stimulating factor) were significantly higher at Ag-challenge
      sites than at B-challenge sites. IL-5 was not detected. In individual chamber
      fluids at Ag-challenge sites, (1) IL-8 levels correlated strongly with levels of
      lactoferrin but not with eosinophil cationic protein levels; (2) RANTES levels
      correlated with numbers of eosinophils but not with eosinophil cationic protein
      levels; and (3) levels of monocyte chemotactic protein-1 correlated weakly with
      histamine released after the first hour. CONCLUSIONS: During LPRs developing
      during the first 5 hours of Ag challenge, there is increased local release of
      several chemokines, which could play roles in the observed attraction and
      subsequent activation of leukocytes and continued histamine release observed at
      such sites.

PMID- 9257796
TI  - Absorption and distribution kinetics of the major Parietaria judaica allergen
      (Par j 1) administered by noninjectable routes in healthy human beings.
AB  - BACKGROUND AND OBJECTIVE: The clinical effectiveness of noninjectable routes for
      specific immunotherapy has been demonstrated in many studies, but no data are
      available on the kinetics of allergens administered by these routes. Therefore we
      studied the kinetics of the radiolabeled purified major Parietaria judaica
      allergen (Par j 1) after sublingual, oral, and intranasal administration to
      healthy human beings. METHODS: After tracer administration (10 to 12.5 microg of
      Par j 1 labeled with iodine 123) to nonallergic volunteers, scintigraphic images
      were recorded at various times. Blood samples were also obtained at serial
      intervals to evaluate the absorption and distribution of radioactivity in plasma
      and to identify circulating radioactive species by molecular exclusion gel
      chromatography. RESULTS: When the sublingual route was used, no circulating
      radioactivity was detected until the tracer was kept under the tongue. The
      labeled allergen was rapidly degraded and absorbed in the gastrointestinal tract
      after swallowing. Plasma radioactivity peaked at about 1.5 to 3 hours and was
      mostly represented by free radioiodine and small radiolabeled peptides. Some
      activity not caused by free 123I remained associated with the oral mucosa up to
      18 to 20 hours after administration. When the oral route was used, the results
      were similar to those observed after swallowing the sublingually administered
      allergen but without any persistence of the tracer in the mouth. When the
      intranasal route was used, the pattern of plasma radioactivity mimicked that of
      the sublingual and oral routes, with absorption of activity from the radiolabeled
      allergen occurring in the gastrointestinal tract after transport to the pharynx
      by mucociliary clearance. A relevant fraction of the tracer was retained on the
      nasal mucosa up to 48 hours after administration. CONCLUSION: The data in this
      study provide the first experimental basis for exploring the in vivo kinetics of
      allergen administered through noninjectable routes for specific immunotherapy in
      human beings.

PMID- 9257795
TI  - Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic
      rhinitis.
AB  - BACKGROUND: Increased serum levels of antigen-specific IgE are often associated
      with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized
      monoclonal antibody, decreases free serum IgE by forming biologically inactive
      immune complexes with free IgE. OBJECTIVE: We hypothesized that rhuMAb-E25 would
      decrease total serum IgE and reduce symptoms. METHODS: Two hundred forty subjects
      were enrolled into five groups to determine the safety, tolerance, and efficacy
      of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic
      rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE.
      One hundred eighty-one subjects received an initial intravenous loading dose (day
      0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in
      mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5
      mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo
      group and an intravenous placebo group were included. The total evaluation time
      included the 84-day treatment period, followed by a 42-day observation period.
      RESULTS: Adverse events were mild, and no differences were observed in the rates
      between the three active and two placebo treatment groups. Ragweed-specific IgE
      levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels
      in a dose- and baseline IgE-dependent fashion. However, only 11 subjects had IgE
      levels that were suppressed to undetectable levels (< or = 24 ng/ml), a sample
      too small to demonstrate significant differences and clinical efficacy. Thus the
      case for efficacy was not proven. Nonetheless, the study confirms that it is safe
      to repeatedly administer rhuMAb-E25 over a period of months. CONCLUSIONS: Because
      rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because
      symptom scores correlated with antigen-specific IgE levels, the results suggest
      that if given in adequate doses, rhuMAb-E25 should be an effective therapy for
      allergic diseases.

PMID- 9257797
TI  - Gelatin-specific humoral and cellular immune responses in children with immediate
      and nonimmediate-type reactions to live measles, mumps, rubella, and varicella
      vaccines.
AB  - BACKGROUND: This study was designed to investigate the development of both
      cellular and humoral immune responses to gelatin in patients with vaccine-related
      immediate and nonimmediate reactions. Our purpose was to define the nature of the
      responses in the different clinical states. METHODS: Six patients with immediate
      reactions and 21 patients with nonimmediate reactions after inoculation of
      various live vaccines were studied. Measurement of gelatin-specific IgE was
      performed in all subjects. Gelatin-specific T-cell responses detected by an in
      vitro lymphocyte proliferation assay and by an assay for IL-2 responsiveness were
      investigated to compare the immune response in patients with the two types of
      reaction. RESULTS: All six patients with immediate reactions had IgE responses to
      gelatin, whereas none of the 21 patients with nonimmediate reactions had any anti
      gelatin IgE. All of the six patients with immediate reactions and 17 of the 21
      patients with nonimmediate reactions exhibited positive T-lymphocyte responses
      specific to gelatin. CONCLUSIONS: Immediate and nonimmediate reactions are caused
      by different types of allergy to gelatin, and cell-mediated immunity to gelatin
      may play an important role in the pathogenesis of nonimmediate reactions.

PMID- 9257798
TI  - Erythema multiforme to phenobarbital: involvement of eosinophils and T cells
      expressing the skin homing receptor.

PMID- 9257799
TI  - Delayed hypersensitivity to thimerosal in RhO(D) immunoglobulin.

PMID- 9257800
TI  - A simple device for deliberate Hymenoptera sting challenge.

PMID- 9257801
TI  - Prevalence of allergic diseases in patients with schistosomiasis mansoni.

PMID- 9257802
TI  - Allergy syndrome after ingestion of salami.

PMID- 9257803
TI  - Atopy and NSAID sensitivity.

PMID- 9257804
TI  - Sting challenge outcome as a selection criterion for venom immunotherapy.

PMID- 9257805
TI  - Specific expression of heterotrimeric G proteins G12 and G16 during human myeloid
      differentiation.
AB  - To evaluate expression of heterotrimeric guanosine triphosphate (GTP)-binding
      proteins (G proteins) in human myeloid cells, we studied expression at the
      protein level of their alpha subunits (G alpha, the subunits responsible for the
      name and specificity of G proteins) in normal human myeloid progenitors and
      mature blood cells. We found that G alpha(s), G alpha(i2), and G alpha(q/11)
      proteins were expressed at high levels at all stages of granulomonocytic and
      erythroid differentiation, whereas expression of G alpha12 and G alpha16 proteins
      in normal myeloid cells was lineage-specific. G alpha12 proteins were expressed
      in erythroid progenitors, monocytes, and platelets, but not in normal
      granulocytic cells. This lineage specificity was lost in leukemic cells: G
      alpha12 proteins were found in human leukemic cells of both granulocytic and
      erythroid lineages. G alpha16 proteins were revealed in myeloid cells as two
      bands (43 and 46 kD), implying that G alpha16 exist in short and long forms. The
      43-kD form was predominant in normal granulomonocytic cells, whereas erythroid
      progenitors and platelets expressed mostly the 46-kD form. Both forms of G
      alpha16 proteins varied during cell differentiation: in normal hematopoietic
      cells, G alpha16 protein expression was high in CD34+ cells, then decreased
      sharply during granulocytic and erythroid differentiation. In leukemic
      granulocytic HL60 and NB4 cells, downregulation of G alpha16 proteins was an
      early event (8 hours) in the process of neutrophil differentiation; in contrast,
      expression of G alpha16 proteins remained high during normal monocytic
      differentiation and in HL60 cells differentiating into monocytes with phorbol
      myristate acetate (PMA) or gamma-interferon (IFNgamma). Finally, we found that
      primary myeloid leukemia blasts, as well as leukemic cell lines, expressed G
      alpha16 proteins at levels higher than those found in normal CD34+ progenitors.
      These observations suggest that it would be worthwhile to investigate a possible
      role for G alpha12 and G alpha16 proteins in the regulation of human
      myelopoiesis.

PMID- 9257806
TI  - alpha-Galactosylceramide (AGL-517) treatment protects mice from lethal
      irradiation.
AB  - AGL-517 (AGL) has an alpha-galactosylceramide structure and is a derivative of
      agelasphin-9b, which in turn is isolated from Agelas mauritianus and has
      immunomodulating activity. When administered before irradiation, AGL has been
      found to increase survival rates in lethally irradiated mice. In this study, we
      found that a single injection of AGL administered within 2 hours of lethal
      irradiation resulted in the long-term survival of mice without bone marrow
      transplantation. Peripheral blood hematology showed that AGL administration
      accelerated the recovery of hematopoietic parameters, including reticulocytes and
      red and white blood cells. Recovery of platelets was moderate. In addition, AGL
      significantly increased the number of endogenous colony forming units-spleen (E
      CFU-S). AGL itself displayed no colony-stimulating activity, but AGL-stimulated
      spleen cell-conditioned medium (AGL-SCM) promoted the proliferation and
      differentiation of bone marrow mononuclear cells from normal mice and Lin marrow
      cells from 5-fluorouracil (5-FU)-treated mice. Using suitable assay systems, we
      analyzed cytokines in AGL-SCM and found significant increases in stem cell factor
      (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM
      CSF), and IL-6 levels compared with control SCM. Additionally, using
      immunoenzymetric assays, we assessed serum levels of these factors in AGL-treated
      mice after lethal irradiation. The serum concentrations of IL-3, GM-CSF, and IL-6
      were substantially elevated, the maximum levels being reached within 2 hours of
      injection. Despite inducing the in vitro increase in SCF, AGL did not elevate
      serum SCF levels. However, certain levels of SCF (approximately 5 ng/mL) were
      detected in mouse serum regardless of irradiation or AGL treatment. When
      irradiated mice were given a cytokine cocktail composed of recombinant murine
      (rm) IL-3, rmGM-CSF, and recombinant human (rh) IL-6 three times a day for 6 days
      (1 microg of each factor per mouse per day) starting 2 hours after irradiation,
      60% of the mice achieved 50-day survival. The radioprotective effect of AGL can
      be attributed, in part, to the cooperative effect of the cytokines induced by AGL
      in vivo. These findings suggest that AGL may be a useful in treating radiation
      induced hematopoietic damage.

PMID- 9257807
TI  - The Wilms' tumor gene is expressed in a subset of CD34+ progenitors and
      downregulated early in the course of differentiation in vitro.
AB  - The Wilms' tumor gene (wt1) is strongly expressed in malignant blasts of acute
      myeloid leukemia (AML) in approximately 80% of all cases. However, the role of
      wt1 expression in non malignant hematopoietic cells remains unclear. To
      characterize the expression of wt1 in differentiating hematopoietic progenitors,
      we isolated and cultured CD34+ progenitor cells from four healthy bone marrow
      donors with stem cell factor (SCF) and granulocyte colony stimulating-factor (G
      CSF) to induce differentiation into granulocytes. Four different cultures were
      carried out for 12 days. During culture, wt1 mRNA expression was analyzed by
      defining its ratio relative to beta-actin using reverse transcriptase polymerase
      chain reaction (RT-PCR). To monitor the stage of differentiation, expression of
      cell surface markers and peroxidase was analyzed daily. The initial purity of
      CD34+ cells ranged between 80% and 90%; after 12 days, the frequency of
      neutrophil bands and segmented neutrophils was approximately 60%. Using RT-PCR to
      determine the ratio of wt1 to beta-actin expression, we reproducibly detected
      maximum expression of wt1 mRNA at day 0 in two cultures and at day 1 in two other
      CD34+ cell cultures; at both these time points nearly all cells fulfilled the
      morphological and immunephenotypical criteria of early hematopoietic blast cells.
      Wt1 expression dropped rapidly at day 1 and 2, respectively, in these two pairs
      of cultures, and was accompanied by an increase of cells expressing CD33 surface
      antigen. Our data suggest that wt1 expression is restricted to a subset of CD34+
      progenitors and downregulated in later stages of differentiation in vitro.

PMID- 9257808
TI  - Differential ability of flt3-ligand, interleukin-11, and Steel factor to support
      the generation of B cell progenitors and myeloid cells from primitive murine
      fetal liver cells.
AB  - A variety of factors produced by stromal fibroblasts, including Flt3-ligand (FL),
      interleukin-11 (IL-11), Steel factor (SF), and IL-7, have been implicated in
      stimulating the production of pre-B cells and myeloid cells from primitive
      hematopoietic precursors. To investigate their relative roles in this process,
      either as single-acting or synergistic agents, we compared the yield and types of
      cells produced after 2 weeks from small numbers of Sca-1+ Lin- (i.e., B220-, Ly-1
      , Gr-1-, and Ter-119-) day 14.5 murine fetal liver cells placed in stromal cell
      free cultures containing all possible combinations of FL, SF, IL-7, and IL-11.
      None of these factors alone supported the production (or survival) of any cells
      beyond 1 week: only pairs of factors consisting of either FL or SF plus either IL
      11 or IL-7 were effective in this regard, with FL plus IL-11 being the most
      potent pair (approximately 7 x 10(4) cells obtained per 100 Sca-1+ Lin- input
      cells). The maximum numbers of cells were produced in the presence of FL, IL-11,
      and IL-7: these included both B220+ and Mac-1+/Gr-1+ cells (approximately 10(6)
      and approximately 2 x 10(5), respectively, per 100 Sca-1+ Lin- input cells). Both
      of these lineages were also obtained with each of the other possible three-factor
      combinations, albeit with variable effectiveness. Omission of either FL or IL-7
      caused the greatest reduction in the yield of B220+ cells (approximately 130-fold
      and approximately 80-fold, respectively). Omission of IL-11 and, to a lesser
      extent, FL caused the greatest reduction in the yield of Mac-1+/Gr-1+ cells
      (approximately 90-fold and approximately 3-fold, respectively). When fetal calf
      serum was replaced with a defined serum substitute, the out put of B220+ cells
      remained the same but myelopoiesis was consistently enhanced (approximately 5- to
      20-fold). These findings support a model involving factor redundancy in the
      extracellular signals required to stimulate the production and amplification of
      both lymphoid and myeloid cells from early Sca-1+ Lin- cells. They also reveal
      quantitative differences in the abilities of different competent factor
      combinations to promote this process, which may be further modulated by the
      presence of undefined serum components.

PMID- 9257809
TI  - Proliferation of LAMA-84 and LAMA-87 cell lines is modulated by autocrine loops
      involving M-CSF and TGF-beta.
AB  - The erythromegakaryocytic cell line (LAMA-84) and the erythroeosinophilic cell
      line (LAMA-87) were used to study receptor expression and receptor-mediated
      response to monocyte/macrophage colony-stimulating factor (M-CSF) and
      transforming growth factor beta (TGF-beta), two modulators of cell proliferation.
      As demonstrated by Northern blot analysis and reverse transcriptase polymerase
      chain reaction (RT-PCR), c-fms and M-CSF mRNA were expressed in both cell lines.
      M-CSF was detected in the supernatant of both cell lines and addition of a
      neutralizing anti-M-CSF antibody inhibited cell growth. The two LAMA cell lines
      were found to express TGF-beta1, -beta2, and -beta3 mRNAs and to secrete TGF-beta
      mostly in latent form. Addition of anti-TGF-beta antibodies to the culture medium
      increased their proliferation, whereas TGF-beta1 inhibited cell proliferation by
      downregulating the c-myc mRNA. These results show that the proliferation of both
      LAMA cell lines is positively and negatively regulated by autocrine mechanisms,
      implying the presence of M-CSF and TGF-beta, respectively. They suggest that
      similar autocrine loops could be involved in the growth regulation of leukemic
      cells in vivo.

PMID- 9257810
TI  - Transduction of retrovirus-mediated NeoR gene into CD34+ cells purified from
      granulocyte colony-stimulating factor (G-CSF)-mobilized infant and cord blood.
AB  - To help establish an effective gene therapy protocol for patients with congenital
      metabolic diseases, we evaluated retrovirus-mediated transduction and long-term
      (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified
      from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood
      (PB) of infant and cord blood (CB). The results were compared with those in bone
      marrow (BM) CD34+ cells. The final purity of the CD34+-enriched fraction from PB,
      CB, and BM, based on FACS analysis, was 88 +/- 14%, 73 +/- 13%, and 68 +/- 19%
      (mean +/- SEM), respectively. Cells were then cultured for 96 hours with
      supernatant containing the vector in the presence of interleukin (IL)-3, IL-6,
      and stem cell factor (SCF). The average efficiency of gene transfer into
      mobilized PB (n = 5) or CB CD34+ cells (n = 6) was significantly higher than that
      into BM CD34+ cells, as measured by G418-resistant colony-forming units for
      granulocyte/macrophage (CFU-GM; 59% or 58% vs. 39%; p < 0.05) and PCR-positive
      CFU-GM (83% or 79% vs. 53%; p < 0.05). When the evaluation was made in an LT
      culture system with irradiated allogeneic marrow stroma, these efficiencies were,
      respectively, 74% or 61% vs. 34% (p < 0.005 or < 0.02) for G418-resistant CFU-GM
      at week 5 of long-term culture, and 88% or 83% vs. 63% (p < 0.05) for PCR
      positive CFU-GM. Fluorometric examination was performed for cell-cycle analysis
      before and after culture, and the results showed that the fraction of cycling
      cells was largest in freshly prepared BM (18%), whereas only a small portion of
      PB (4.6%) and CB (2%) was cycling. However, this value was 17% in BM, 22% in PB,
      and 13% in CB after culture. These results suggest that mobilized PB from small
      children and CB cells are suitable and realistic targets for clinical gene
      therapy and that tandem transduction procedures can be achieved by combining CB
      and PB.

PMID- 9257811
TI  - Mouse bone marrow stromal cell line MC3T3-G2/PA6 with hematopoietic-supporting
      activity expresses high levels of stem cell antigen Sca-1.
AB  - The murine clonal preadipose cell line, MC3T3-G2/PA6 (PA6), has the ability to
      support in vitro proliferation of hematopoietic stem cells defined as colony
      forming units in spleen (CFU-S). In order to ascertain the relationship between
      the hematopoietic-supporting activity of PA6 cells and their expression, we
      cultured a number of these cells for over 45 weeks and investigated the level at
      which they expressed several cell surface markers and membrane-bound growth
      factors. Besides expressing stem cell factor (SCF) and macrophage colony
      stimulating factor (M-CSF), PA6 cells were found by flow cytometry analysis to
      express high levels of stem cell antigen-1 (Sca-1). The expression level of Sca-1
      in PA6 cells correlated with the ability of the latter to support hematopoiesis,
      whereas no such correlation was observed in the case of SCF and M-CSF expression.
      A cDNA clone encoding the protein recognized by anti-Sca-1 antibody was isolated
      from PA6 cells by expression cloning, so that its nucleotide sequence encoded the
      protein identical to mouse alloantigen Ly-6A.2. Genetically engineered COS-7
      cells, transformed by the expression vector carrying the Ly-6A.2 gene, suppressed
      proliferation of murine lineage marker-negative (Lin) bone marrow cells by
      themselves and synergistically augmented proliferation of these cells in the
      presence of SCF. These results suggest that Ly-6A.2 regulates the proliferation
      of hematopoietic progenitor cells, and is one of the molecules organizing the
      hematopoietic microenvironment provided by stromal cells.

PMID- 9257812
TI  - A clinically suitable ex vivo expansion culture system for LTC-IC and CFC using
      stroma-conditioned medium.
AB  - FACS-selected CD34+ HLA-DR- cells (DR- cells) may provide a source of benign stem
      cells suitable for autografting in chronic myelogenous leukemia (CML) and other
      hematological malignancies. However, DR- cell selection depletes the majority of
      committed hematopoietic progenitors, which may be important for early
      engraftment. Furthermore, only a small number of DR- cells may be selectable in
      certain patients. These impediments to the use of DR- cells for autografting may
      be overcome through the development of ex vivo culture systems that support
      expansion and initial differentiation of primitive progenitors. Because 2-week
      culture of DR- cells in a stroma "noncontact" system supplemented with
      interleukin-3 (IL-3) and macrophage inflammatory protein 1-alpha (MIP-1alpha)
      expands both long-term culture-initiating cells (LTC-ICs) and colony-forming
      cells (CFCs), we adapted this system to a clinically applicable method for
      expanding LTC-ICs and CFCs ex vivo. In initial small-scale studies, DR cells were
      grown in stroma conditioned medium (SCM) supplemented with IL-3 with or without
      additional growth-promoting cytokines and the chemokines PF-4 and BB10010, all
      approved for clinical use. An IL-3 dose-dependent expansion of committed
      progenitors and LTC-ICs was observed when DR- cells were cultured in tissue
      culture plates in SCM+IL-3 for 2 weeks. Similar CFC expansion along with
      increased (5-fold) LTC-IC expansion was observed following addition of PF-4 to
      SCM+IL-3 cultures. The addition of stem cell factor (SCF), but not of IL-6, IL
      11, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)
      CSF, IL-1, and IL-7, increased CFC and LTC-IC expansion beyond the levels
      observed with SCM+IL-3 alone. We next evaluated the suitability of this culture
      system for scale-up. Culture of 2-6 x 10(5) DR- cells in gas-permeable bags with
      SCM+IL-3 resulted in similar CFC and LTC-IC expansion as seen in small-scale
      cultures. In addition, we observed that progenitors capable of differentiating to
      natural killer (NK)-cells were maintained under these conditions. Finally, we
      found that BCR/ABL mRNA-negative CFCs and LTC-ICs present in DR- cells selected
      from steady-state CML marrow could be expanded in large-scale SCM+IL-3 cultures.
      We conclude that culture of DR- cells for 2 weeks in SCM+IL-3 culture, with or
      without PF-4 or SCF, results in significant CFC and LTC-IC expansion and lymphoid
      NK progenitor maintenance. This culture system is readily adaptable to the
      expansion of primitive progenitors for autotransplantation.

PMID- 9257813
TI  - Thymic and extrathymic differentiation and expansion of T lymphocytes following
      bone marrow transplantation in irradiated recipients.
AB  - Thymic function is severely impaired in most marrow transplant recipients. To
      evaluate the impact of thymic hypoplasia on T cell reconstitution following
      marrow transplantation, we compared the phenotype and function of T lymphocytes
      in thymectomized recipients with those of euthymic hosts. Irradiated C57BL/6 mice
      (Thy1.2+, Ly5.1+) received 10(7) T cell-depleted B6.Ly5.2 bone marrow cells
      (Thy1.2+, Ly5.2+), with or without 3 x 10(5) B6.PL lymph node cells (Thy1.1+,
      Ly5.1+) as a source of T lymphocytes. Multiparameter flow cytometry analysis
      showed that in euthymic mice (group 1), T cell reconstitution was carried out by
      donor hematopoietic stem cells that differentiated in the host's thymus, whereas
      the production of chimeric T cells in athymic recipients depended on the presence
      or absence of T cells in the graft. When T lymphocytes were present in the graft
      (group 2), their progeny constituted the vast majority of splenic T cells on day
      100 posttransplant. When the graft did not contain T lymphocytes (group 3), T
      cell reconstitution resulted from extrathymic maturation of donor hematopoietic
      progenitors; T cells differentiating along this pathway expressed lower levels of
      T cell receptor and a large proportion of the CD8+ subset expressed CD8alpha
      alpha homodimers. The T cell receptor Vbeta profile of all chimeras was similar
      to that of normal C57BL/6 mice. Compared with T cells found in euthymic
      recipients, those in mice from groups 2 and 3 were less abundant (particularly
      with respect to the CD4+ subset), displayed the CD44/CD45 phenotype of activated
      memory cells, and expressed high levels of IL-2 receptor beta chain. These
      results show that both the presence or absence of the thymus and the composition
      of the grafted inoculum determine the source and extent of posttransplant T cell
      reconstitution. Because they determine the nature of the differentiation pathway
      taken during T cell development in the host, these two factors can exert a
      critical influence on the appearance of graft vs. host disease and the level of
      host immunocompetence.

PMID- 9257814
TI  - Sequential treatment with rmIL-3 or simultaneous treatment with rmIL-3 or rhIL-11
      with thrombopoietin (TPO) fails to enhance in vivo neonatal rat
      thrombocytopoiesis.
AB  - Multipotent-lineage nondominant growth factors, acting alone or in combination
      with lineage-dominant cytokines, are known to influence both myelopoiesis and
      thrombocytopoiesis. Interleukin (IL)-3 and IL-11 stimulate and expand
      multilineage progenitor cells and induce thrombocytopoiesis. These cytokines also
      act synergistically with various other lineage dominant and lineage-nondominant
      cytokines in vitro to expand primitive and committed hematopoietic stem cells. In
      this study we investigated the in vivo effects of IL-3 and IL-11 in combination
      with the c-mpl ligand, thrombopoietin (rhTPO), on neonatal rat hematopoiesis.
      Newborn Sprague-Dawley rats (24 36 hours old, weighing 6-8 g) were
      intraperitoneally injected with rhTPO (10 microg/kg) for 14 days, rmIL-3 (10
      microg/kg) for 5 days followed by rhTPO (10 microg/kg) for 9 days, rmIL-3 (10
      microg/kg) + rhTPO (10 microg/kg) for 14 days, rhIL-11 (250 microg/kg) + rhTPO
      (10 microg/kg) for 14 days, or PBS/human serum albumin (HSA) for 14 days. When
      compared with PBS/HSA, rhTPO at a dosage of 10 microg/kg significantly increased
      platelet count (10(-9) L) (day 6, 569 +/- 37.1 vs. 1446 +/- 43.8, p < 0.001; day
      10, 796 +/- 68.3 vs. 1774 +/- 238.4, p < 0.01; day 14, 850 +/- 64.4 vs. 3441 +/-
      98.1 /10(-9) l, p < 0.001) and absolute neutrophil count (ANC) (day 6, 335.2 +/-
      59.6 vs. 752 +/- 335.2, p < 0.01; day 12, 664 +/- 54.1 vs. 1520 +/- 158.2, p <
      0.01). However, rhTPO has no effect on the circulating hematocrit or red blood
      cell count. RhTPO-treated animals also displayed higher platelet counts (/10(-9)
      L) vs. rhIL-11 or rhIL-6 beginning on day 6 (day 6, 1597.6 +/- 134.7 vs. 930.7 +/
      67.3 vs. 863 +/- 19.6, p < 0.01; day 8, 1686 +/- 208.4 vs. 990 +/- 29.4, vs. 977
      +/- 34.33, p < 0.05; day 10, 1774 +/- 238.4 vs. 1096 +/- 49.6, vs. 937 +/- 65, p
      < 0.01; day 14, 2187 +/- 127.5 vs. 1280 +/- 35.8 vs. 951 +/- 50.7 /10(-9) L, p <
      0.01). Sequential administration of rmIL-3 followed by rhTPO resulted in no
      significant increase in platelet counts compared with PBS-HSA/rhTPO. RhTPO + rmIL
      3 given simultaneously also had no additive effect on the circulating platelet
      count compared with rhTPO alone. Similarly, no additive effect on circulating
      platelet counts was observed with rhIL-11 + rhTPO vs. rhTPO alone. Bone marrow
      studies showed a significant increase in the number of megakaryocytes per high
      power field in all the groups treated with rhTPO vs. control (p < 0.05), but no
      additive effect was seen in neonatal rats additionally receiving either rmIL-3 or
      rhIL-11. Colony forming unit (CFU)-Meg colony formation was also significantly
      increased in all the groups treated with rhTPO vs. control (p < 0.05), with no
      additive effect observed after the addition of either rmIL-3 or rhIL-11. These
      data suggest that rhTPO is more effective than rmIL-3 or rhIL-11 in inducing
      neonatal in vivo thrombocytopoiesis in rats, and that no additive effect is to be
      expected when rhTPO is combined sequentially with rhIL-3 or simultaneously with
      either rmIL-3 or rhIL-11. We hope that these preclinical data will provide
      insight into the design and future application of these thrombopoietic cytokines,
      alone or in combination, to prevent or treat thrombocytopenia.

PMID- 9257815
TI  - Lactate dehydrogenase-elevating virus (LDV): lifelong coexistence of virus and
      LDV-specific immunity.
AB  - Viruses have developed various strategies to coexist with vertebrate hosts.
      Lactate dehydrogenase-elevating virus (LDV) is a highly cytopathic virus
      exhibiting an extraordinary rate of replication; LDV nevertheless establishes a
      persistent infection without harming the host. The cytotoxic and helper T cell
      responses to LDV were monitored in mice with different genetic backgrounds. LDV
      specific cytotoxic and helper T cells were found in all strains tested. These
      responses persisted for at least up to 250 days despite high levels of LDV in the
      blood. Thus, the cytopathic LDV induces and maintains an inefficient immune
      response that is not exhausted. LDV infection in mice reveals a special type of
      host-virus equilibrium where LDV quickly establishes persistence despite
      continuously induced LDV-specific helper and cytotoxic T cell responses, which
      apparently are too slow to control the highly cytopathic and extremely fast
      replicating virus.

PMID- 9257816
TI  - Identification and characterization of a novel beta chemokine containing six
      conserved cysteines.
AB  - The chemokines are emerging as a diverse and expanding family of cytokines. In
      this study, we report the identification of a novel beta (CC) chemokine that
      exhibits an unusual pattern of six conserved cysteines and was thus designated
      6Ckine. The primary amino acid sequence of 6Ckine is highly conserved in humans,
      mice, and pigs and contains the expected four cysteines characteristic of the
      beta chemokine family plus two additional carboxyl-terminal cysteines. Expression
      of human 6Ckine appears to be restricted to lymphoid organs, particularly lymph
      node, spleen, and appendix, while murine 6Ckine has a broader tissue distribution
      with the highest mRNA levels found in spleen and lung. Recombinant murine 6Ckine
      was chemotactic in vitro for thymocytes and activated T cells, but not for B
      cells, macrophages, or neutrophils. Together these data demonstrate that 6Ckine
      is a novel member of the chemokine superfamily.

PMID- 9257817
TI  - Human monocytic cells contain high levels of intracellular Fas ligand: rapid
      release following cellular activation.
AB  - Human monocytes express both Fas and Fas ligand (FasL) on the cell surface, and
      the interaction of these molecules induces spontaneous apoptosis. In this report
      we present a study of monocytic cells by FACS and confocal microscopy using anti
      FasL Abs that reveals high levels of preformed FasL within the intracellular
      compartment. Further analysis by immunoblotting of cell cytoplasmic proteins
      confirmed the presence of a 37-kDa protein recognized by anti-FasL Abs.
      Stimulation of the monocytic cells with immune complexes, PHA, or superantigen
      gave rise to the rapid release of soluble FasL from within the cells. The
      presence of high levels of FasL within human monocytes suggests that, upon
      stimulation, the cells can rapidly translocate intracellular FasL to the cell
      surface and release it into the extracellular milieu. These findings indicate a
      novel mechanism for monocytes to respond rapidly to environmental changes,
      resulting in the release of active, soluble FasL.

PMID- 9257818
TI  - IL-4 expression by grafts from transgenic mice fails to prevent allograft
      rejection.
AB  - Cell-mediated tissue destruction, such as that occurring in allograft rejection,
      is thought to be mediated by Th1 cells and cytokines. We have recently shown that
      transgenic expression of the Th2 cytokine IL-4 by pancreatic beta cells
      completely protects nonobese diabetic (NOD) mice from autoimmune diabetes by
      inducing functional tolerance among autoreactive T cells. To investigate whether
      local IL-4 production could also induce functional tolerance among alloreactive T
      cells and thus prevent allograft rejection, we transplanted pancreata from
      transgenic neonatal mice and their nontransgenic littermates into allogeneic
      hosts. Within 2 wk, recipient mice had rejected their grafts regardless of the
      transgene's presence or absence. Considering that the vigorous immune response
      induced might have prevented any effect by IL-4, we injected recipient mice with
      anti-CD4 and anti-CD8 mAbs, thereby depleting them of T cells and thus providing
      the islets with an opportunity to mature and grow. This approach indeed delayed
      rejection of neonatal pancreata from nontransgenic mice by >1 wk. By that time,
      however, pancreata from transgenic mice had also been rejected. Our results
      indicate that the allograft rejection response under these conditions, in
      contrast to the autoimmune response in NOD mice, cannot be regulated by local IL
      4 production, regardless of the cytokine's impact on Th1 cells.

PMID- 9257819
TI  - IL-12 production by central nervous system microglia is inhibited by astrocytes.
AB  - IL-12, a 75-kDa heterodimeric cytokine composed of two chains (p35 and p40), is a
      central regulator of immune responses and may be implicated in the pathogenesis
      of certain inflammatory diseases of the central nervous system (CNS). We have
      examined the capacity of two CNS APC, microglia and astrocytes, to produce IL-12
      upon stimulation with cytokines, LPS, or a neurotropic virus. In purified
      microglial cultures from neonatal mouse brains, expression of IL-12 p35 and p40
      mRNA is induced by LPS and is stimulated maximally by combined IFN-gamma/LPS
      treatment, as detected by semiquantitative reverse-transcriptase PCR. LPS induces
      secretion of IL-12 p40, but not of IL-12 p75, as detected by specific ELISA.
      Combined stimulation with IFN-gamma/LPS enhances IL-12 p40 secretion and induces
      IL-12 p75 secretion by microglia. Conversely, mouse astrocytes do not express IL
      12 p35 mRNA and do not secrete IL-12 p75 under any condition tested. IL-12
      production by activated microglia is inhibited by IL-10, PGE2, and cAMP-elevating
      agents. Coculture of microglia with astrocytes or exposure of microglia to
      astrocyte-conditioned medium also results in marked reduction of IL-12 p75 and
      p40 secretion by IFN-gamma/LPS-stimulated microglia, indicating a regulatory role
      of astrocytes on IL-12 production. This novel mechanism of IL-12 regulation may
      play an important role in the control of immune responses during infection or in
      Th1 cell-mediated autoimmune diseases of the CNS.

PMID- 9257820
TI  - Cot kinase regulation of IL-2 production in Jurkat T cells.
AB  - tpl-2 is a rat gene that encodes a serine/threonine protein kinase that can act
      as a novel mitogen-activated protein (MAP) kinase kinase kinase. Tpl-2 is
      activated in Moloney murine leukemia virus-induced rat T lymphomas, due to a
      truncation in the C-terminal region of the protein. cot is a very closely related
      gene, if not the human homologue. The truncated form of Cot has been shown to
      have a higher transforming activity than the nontruncated form. In this paper we
      show that an increase in truncated Cot kinase expression correlates with an
      increase in IL-2 production in anti-CD3-treated Jurkat cells. Truncated Cot
      expression also cooperates with PHA or phorbol 12,13-dibutyrate (PDBu) and
      calcium ionophore for IL-2 production in Jurkat cells. Both the truncated and
      nontruncated Cot forms increased IL-2 transcription because they enhanced
      transcription of a reporter gene linked to the IL-2 promoter. The expression of a
      dominant negative form of Cot inhibits transcription directed by the IL-2
      promoter in Jurkat cells stimulated by PDBu and ionophore. These data suggest a
      role of Tpl-2/Cot kinase in IL-2 production during T lymphocyte activation and
      could also explain its role in Moloney murine leukemia virus-induced
      lymphomagenesis.

PMID- 9257821
TI  - Modulation of lymphocyte interaction with endothelium and homing by HIV-1 gp120.
AB  - We have previously shown that HIV-1 glycoprotein 120 (gp120) induces CD4
      association with several molecules on the surface of CD4+ lymphocytes. Since one
      of these molecules was CD38, involved in lymphocyte/endothelium interaction, this
      article examines the possibility that gp120/CD4 binding alters CD4+ T cell
      interaction with vascular endothelium in vitro and in vivo. Cocapping experiments
      showed that gp120 induced CD4 association with CD38, CD29, CD49d, and CD11a in
      peripheral blood CD4+ T cells. Two in vitro binding assays were used to evaluate
      the effect of gp120. A static binding assay, performed at 37 degrees C, evaluated
      stable interactions mediated by integrins, and a dynamic binding assay, performed
      at 4 degrees C on a rocking shelf, evaluated weak interactions mediated by
      constitutively active molecules such as selectins and CD38. Gp120 increased
      dynamic binding and inhibited static binding to the endothelium of peripheral
      blood CD4+ T cells and SUPT-1 cells. Binding inhibition with mAbs suggested that
      the gp120 effect on dynamic binding involved CD38, CD31, and CD49d, whereas the
      effect on static binding involved CD11a and CD49d. In vivo experiments showed
      that treatment of 2D4 cells, a CD4- CD8- mouse T cell clone transfected with the
      human CD4, with gp120 increased their homing into the spleen, intestine, and
      mesenteric lymph nodes, whereas it decreased homing into peripheral lymph nodes.
      Alteration of lymphocyte homing may contribute to immune deficiency in HIV-1+
      patients by decreasing the probability of an encounter between Ags and
      lymphocytes and inhibiting the spread of effector lymphocytes into tissues.

PMID- 9257822
TI  - Ion channels, Ca2+ signaling, and reporter gene expression in antigen-specific
      mouse T cells.
AB  - Whole cell recordings were performed in parallel with measurements of
      intracellular Ca2+ ([Ca2+]i) and gene expression using the murine T cell
      hybridoma, B3Z, a cell line stably infected with a lacZ reporter gene, driven by
      the minimal IL-2 promoter (NF-AT, nuclear factor of activated T cells). The
      physiologic roles of ion channels in B3Z cells were investigated by correlating
      the pharmacology of channel block with [Ca2+]i, and expression of lacZ. In B3Z
      cells and activated human T cells, the major component of voltage-gated K+ (K(V))
      current had biophysical and pharmacologic properties associated with type n
      channels encoded by Kv1.3; a minor K(V) component was charybdotoxin (CTX)
      resistant. Ca2+-activated K+ (K(Ca)) current was sensitive to CTX, but not to
      margatoxin (MgTX). Inwardly rectifying K+ (K(IR)) current was blocked completely
      by 200 microM of Ba2+. Outwardly rectifying Cl- currents were induced by cell
      swelling. An inwardly rectifying Ca2+ current (I(CRAC)) was activated by
      dialyzing the cell with 10 mM EGTA and 10 microM IP3. CTX reduced thapsigargin
      stimulated [Ca2+]i signaling and gene expression by approximately 25%. Although
      the thapsigargin-stimulated [Ca2+]i signal was resistant to complete inhibition
      by K+ channel blockers, it was very sensitive to the K+ diffusion potential and
      Cl- removal, suggesting that drug-resistant K+ channels and perhaps Cl- channels
      can maintain a sufficiently negative membrane potential to drive Ca2+ influx.
      Neither [Ca2+]i signaling nor gene expression induced by stimulation of the CD3
      epsilon subunit of the TCR was inhibited by ion channel blockers used in this
      study. We conclude that several channel types can contribute to maintenance of
      Vm, Ca2+ signals, and gene expression.

PMID- 9257823
TI  - Three domains of SLP-76 are required for its optimal function in a T cell line.
AB  - We and others have shown that overexpression of SLP-76 augments TCR-stimulated IL
      2 promoter activity in the Jurkat T cell line. In this report we investigate the
      signaling mechanisms through which SLP-76 mediates its effect on T cell
      activation. We show that overexpressed SLP-76 acts downstream of TCR-stimulated
      protein tyrosine kinases, but does not affect calcium signaling. Overexpression
      of SLP-76 does, however, augment TCR stimulation of both ERK (extracellular
      signal-regulated kinase) activity and a reporter construct driven by activating
      protein-1 binding sites. Structure/function analysis reveals that three distinct
      regions of SLP-76, each important for protein associations, are required for
      augmentation of TCR-induced nuclear factor-AT activity. These data suggest that
      SLP-76 functions as an adapter molecule that requires three unique domains to
      link proximal TCR signals in T cells.

PMID- 9257824
TI  - Degenerate and promiscuous recognition by CTL of peptides presented by the MHC
      class I A3-like superfamily: implications for vaccine development.
AB  - Recent data demonstrate that HLA class I alleles can be grouped into
      superfamilies based on similarities of their peptide-binding motifs. In this
      study, we have tested the immunogenicity and antigenicity of peptides capable of
      degenerate binding to multiple HLA class I molecules of the A3-like superfamily.
      The assay systems utilized included both primary in vitro cultures of lymphocytes
      from healthy donors, as well as in vitro restimulation of lymphocytes from HIV
      infected individuals. Several of the peptides capable of binding more than one
      HLA A3-like class I molecule were also found to be immunogenic in the context of
      this same group of A3-like molecules (degenerate CTL recognition). Furthermore,
      some of the CTL lines thus generated demonstrated promiscuous recognition of the
      cognate epitope in the context of MHC molecules from more than one member of the
      superfamily. The fine Ag specificity of this phenomenon was further analyzed
      using two promiscuous CTL clones derived from A3 and A11 individuals,
      respectively, and specific for an epitope in the HIV-1 reverse transcriptase. By
      the use of single-amino acid-substitution analogues, it was demonstrated that the
      fine specificity of the TCR is largely maintained between MHC-matched and MHC
      mismatched presentation of peptide within the A3-like superfamily. These results
      indicate that the similar peptide-binding specificities among different members
      of the A3-like superfamily can be reflected in a remarkable similarity in the
      peptide-MHC complex structures engaged by the TCR and responsible for T cell
      activation.

PMID- 9257825
TI  - Characterization of IL-12 receptor beta1 chain (IL-12Rbeta1)-deficient mice: IL
      12Rbeta1 is an essential component of the functional mouse IL-12 receptor.
AB  - Two chains of the IL-12R, IL-12Rbeta1 and IL-12Rbeta2, have recently been cloned.
      To determine the role of IL-12Rbeta1 in mediating the biologic functions of IL-12
      in mice, we have generated IL-12Rbeta1-deficient (IL-12Rbeta1(-/-)) mice by
      targeted mutation in ES cells. Con A-activated splenocytes from IL-12Rbeta1(+/+)
      mice displayed both high and low affinity IL-12-binding sites, whereas Con A
      activated splenocytes from IL-12Rbeta1(-/-) mice expressed only low affinity IL
      12-binding sites. Consistent with the expression of low affinity IL-12-binding
      sites on IL-12Rbeta1(-/-) lymphoblasts, these cells expressed normal amounts of
      IL-12Rbeta2 mRNA. Unlike those from IL-12Rbeta1(+/+) mice, Con A-activated
      splenocytes from IL-12Rbeta1(-/-) mice failed to proliferate or produce IFN-gamma
      in response to IL-12, even at very high concentrations (67 nM). In contrast,
      lymphoblasts from both types of mice proliferated equally well to IL-2 or IL-7.
      Splenocytes from IL-12Rbeta1(-/-) mice also failed to display enhanced NK lytic
      activity when cultured with IL-12 but responded normally to IL-2. Similar to IL
      12 p40-deficient mice, IL-12Rbeta1(-/-) mice were impaired in their ability to
      produce IFN-gamma in response to endotoxin administration in vivo, and IL
      12Rbeta1(-/-) splenocytes were deficient in IFN-gamma secretion when stimulated
      with either Con A or soluble anti-CD3 mAb in vitro. These results demonstrate
      that IL-12Rbeta1 is required for mouse T and NK cells to respond to IL-12 and
      that expression of low affinity IL-12-binding sites, presumably reflecting
      expression of IL-12Rbeta2, is by itself insufficient to mediate IL-12
      responsiveness, even in the presence of very high concentrations of IL-12.

PMID- 9257826
TI  - Introduction of soluble proteins into the MHC class I pathway by conjugation to
      an HIV tat peptide.
AB  - Protection against most intracellular pathogens requires T cells that recognize
      pathogen-derived peptides in association with MHC class I molecules on the
      surface of infected cells. However, because exogenous proteins do not ordinarily
      enter the cytosol and access the MHC class I-processing pathway, protein-based
      vaccines that induce class I-restricted CTL responses have proved difficult to
      design. We have addressed this problem by conjugating proteins, such as OVA, to a
      short cationic peptide derived from HIV-1 tat (residues 49-57). When APC were
      exposed in vitro to such protein conjugates, they processed and presented the
      peptides in association with MHC class I molecules and stimulated CD8+ Ag
      specific T cells. Moreover, Ag-specific CTLs were generated in vivo by immunizing
      mice with histocompatible dendritic cells that had been exposed to protein-tat
      conjugates.

PMID- 9257827
TI  - Weak peptide agonists reveal functional differences in B7-1 and B7-2
      costimulation of human T cell clones.
AB  - The influence of costimulation on the T cell response to altered peptide ligands
      that act as either partial or weak agonists for human CD4+ T cell clones was
      examined. Using stable Chinese hamster ovary (CHO) cell transfectants expressing
      DR2 (DRB1*1501) and human B7-1 or B7-2 as APC, presentation of native myelin
      basic protein (MBP) p85-99 peptide Ag or a partial agonist of MBP p85-99 induced
      equivalent T cell activation as measured by [3H]TdR incorporation and cytokine
      secretion. In marked contrast, presentation of cross-reactive peptides of MBP p85
      99 that act as weak agonists with B7-1, but not B7-2, costimulation resulted in
      significant T cell activation as measured by [3H]TdR incorporation and cytokine
      secretion. These data suggest that decreasing the strength of the signal provided
      to the TCR allows differences in B7-1 and B7-2 signaling to be observed. Thus,
      the costimulatory environment during T cell activation may be a mechanism of
      regulating T cell cross-reactivity in the periphery.

PMID- 9257828
TI  - Augmentation of mature CD4+ T cell responses to isolated antigenic class II
      proteins by fibronectin and intercellular adhesion molecule-1.
AB  - Mature CD4+ T cells can undergo stable adhesion to isolated antigenic MHC
      complexes, and upon TCR engagement exhibit up-regulated adhesion to the integrin
      ligands fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1). Here, we
      have examined T cell responses to purified antigenic class II complexes, alone or
      coimmobilized in the presence of FN or ICAM-1. T cell adhesion to immobilized
      peptide-MHC complexes alone stimulated suboptimal, but marked levels of IFN-gamma
      and IL-2 secretion, and this was accompanied by cell proliferation. T cell
      adhesion to both FN and ICAM-1 strongly augmented cytokine release and T cell
      proliferation. Activation of Vbeta3+ and Vbeta8+ T cell lines by isolated
      staphylococcal enterotoxin-MHC complexes was also examined, and surprisingly, a
      Vbeta8+ T cell line displayed significant cell adhesion or later response to
      staphylococcal enterotoxin B-MHC complexes only when Ag was coimmobilized with
      ICAM-1 or FN. The results demonstrate that adhesion of CD4+ T cells to ICAM-1 or
      FN activated by natural TCR ligands can strongly augment T cell signaling and
      downstream responses. Moreover, for some Ags, T cell interaction with accessory
      ligands may be critical in attaining a threshold level of receptor occupancy for
      cell activation.

PMID- 9257829
TI  - Mechanisms of L-selectin regulation by activated T cells.
AB  - The activation of T cells through the TCR results in the differential regulation
      of a set of adhesion molecules that dramatically alters lymphocyte migration and
      tissue localization properties in vivo. L-selectin, the lymph node homing
      receptor, is central to the control of lymphocyte recirculation. We examined the
      regulation of L-selectin as a function of time after activation in vitro. Within
      an hour of stimulation, T cells down regulate L-selectin, with a 90% loss by 4 h,
      due to accelerated proteolytic cleavage. Over the course of the following 48 h,
      surface receptor expression increases markedly. This is due to an increase in L
      selectin mRNA, which, in turn, results from increased message stability. During
      the next several days after activation, L-selectin levels decrease, resulting in
      L-selectin-negative T cells by 5 to 7 days after stimulation. This decrease
      occurs faster in CD8 than in CD4 T cells. During this phase of regulation, L
      selectin message remains stable even as the level of specific mRNA continuously
      decreases. This indicates that the L-selectin-negative phenotype of T cells late
      after activation is due to the down-regulation of gene transcription. These
      results demonstrate that after stimulation through the TCR, the expression of L
      selectin changes in a triphasic pattern, with an initial marked decrease,
      followed by a transient phase of superinduction and then a loss of expression.
      These changes are regulated through the complex interactions between several
      mechanisms at the transcriptional, post-transcriptional, and protein turnover
      levels.

PMID- 9257830
TI  - The avian chB6 (Bu-1) alloantigen can mediate rapid cell death.
AB  - The control of cell death is critical in the immune system. T and B lymphocytes
      must be censored during their development to remove nonfunctional or self
      reactive lymphocytes. However, the molecules controlling cell deletion during
      lymphopoiesis have not been defined. B cells removed from the avian bursa of
      Fabricius rapidly undergo cell death in culture. We screened bursal B cells with
      a panel of Abs and lectins to identify molecules affecting their viability. Abs
      to the chB6 alloantigen caused a rapid loss of cell viability as measured by
      staining with propidium iodide. ChB6 Abs also cause adhesion between B cells.
      Transfection of cDNA encoding chB6 reconstituted the allele-specific cell death
      and adhesion effects in avian cell lines. These effects can be separated by
      binding cells onto Ab-coated plastic dishes. In these experiments, cells were
      killed in the absence of cell:cell contact. The ability of chB6 cross-linking to
      evoke cell aggregation and cell death is also observed when chB6 is expressed in
      growth factor-dependent mammalian cells. In these cells growth factor can almost
      completely prevent cell death but not cell aggregation. This suggests that known
      cell survival stimuli can suppress the cell death brought about by chB6 cross
      linking. These results show that chB6 may have an important role in controlling
      cell survival and/or adhesion during avian B cell development.

PMID- 9257831
TI  - Peptide antigen or superantigen-induced down-regulation of TCRs involves both
      stimulated and unstimulated receptors.
AB  - T cell activation by peptide/MHC complexes, superantigens, or mAbs induces the
      down-regulation of cell surface TCRs. We addressed the question of whether TCR
      down-modulation affects only TCRs that had directly interacted with their ligand
      or whether down-modulation could also affect TCRs that had not interacted with
      their ligand. To this end, we generated T cells coexpressing equal levels of two
      different TCRs by transfecting the appropriate cDNAs into cells of the human T
      cell line, Jurkat. Each set of TCRs can be distinguished by means of anti-Vbeta
      mAbs and can be stimulated separately with peptide Ag, bacterial superantigens,
      or mAbs. We found that activation of these cells with each of these stimuli down
      modulated not only directly stimulated TCR complexes but also unstimulated ones.
      Comodulation of stimulated and unstimulated receptors may reflect functional
      interactions between surface TCRs that could take place during Ag or superantigen
      recognition by T cells without the need for ligand cross-linking. Consistent with
      this idea, both stimulated and unstimulated receptors colocalized in patches on
      the cell surface after activation.

PMID- 9257832
TI  - CD28-B7 T cell costimulatory blockade by CTLA4Ig in sensitized rat recipients:
      induction of transplantation tolerance in association with depressed cell
      mediated and humoral immune responses.
AB  - We tested the effects of blocking CD28-B7 T cell costimulation by using CTLA4Ig
      in an established transplantation model in which LBNF1 cardiac allografts are
      rejected in an accelerated manner (<36 h) by LEW rats presensitized with Brown
      Norway skin grafts. Treatment with CTLA4Ig with or without donor alloantigen in
      the sensitization phase (between skin and cardiac engraftment) minimally delayed
      accelerated rejection. However, adjunctive infusion of CTLA4Ig and donor
      alloantigen in the effector phase (after cardiac engraftment) resulted in long
      term graft survival and donor-specific tolerance in 30 to 50% of the recipients.
      The mutant form of CTLA4Ig, which blocks B7-1 but not B7-2, was ineffective. The
      tolerant state was accompanied by reduction of cell-mediated (MLR/CTL) responses
      and depression of humoral (circulating IgM/IgG allo-Abs) alloreactivity in vivo.
      Hence, the binding of CD28 on T cells to both CD80 and CD86 ligands represents a
      crucial initial costimulatory step leading to accelerated graft rejection.
      CTLA4Ig-mediated early blockade of the CD28 signaling pathway combined with
      transfusion of donor cells in the perioperative period interrupts sensitization
      and may produce transplantation tolerance. This regimen inhibits T cell
      costimulation and activation to provide help to CD8+ cytotoxic T and B cells,
      perhaps, via CTLA4Ig-induced clonal anergy or deletion.

PMID- 9257833
TI  - Recombinant soluble alphabeta T cell receptors protect T cells from immune
      suppression: requirement for aggregated multimeric, disulfide-linked alphabeta
      heterodimers.
AB  - Recombinant soluble T cell receptors (sTCR) protected contact sensitivity (CS)
      effector T cells from down-regulation or immunosuppression. CS-protecting sTCR
      were released enzymatically from the surface of thymoma cells transfected with
      cDNAs encoding TCR-alpha and -beta extracellular domains that were expressed with
      a phosphatidylinositol linkage. sTCR affinity purified on anti-TCR-alpha and anti
      TCR-beta mAb columns had identical CS-protective activity, as did sTCR from a
      CD4+ Th2 clone or from a CD8+ cytotoxic clone. Reduced sTCR alpha- and beta
      chains had no CS-protective activity, but this was restored when the TCR chains
      were rejoined into disulfide-linked alphabeta heterodimers. sTCR CS protection
      was Ag nonspecific, MHC unrestricted, and not influenced by the relevant
      synthetic peptide specific for the TCR complexed with appropriate MHC. CS
      protection may have resided in the sTCR constant region. When heated at 62
      degrees C for 30 min, sTCR formed a CS-protecting aggregate, with a molecular
      mass of 481 +/- 37 kDa, corresponding to an alphabeta TCR pentamer. HPLC gel
      filtration essentially confirmed the molecular mass at 516 kDa for the multimer,
      while the monomer, which was an alphabeta TCR heterodimer, had an expected
      molecular mass of approximately 104 kDa and no bioactivity. In summary, the
      pentameric sTCR may bind to and activate lymphoid cells, perhaps via constant
      domains, resulting in protection of CS effector T cells from down-regulation. The
      ability of sTCR to protect CS effector T cells from down-regulation/suppression,
      if generalized, could overcome immunosuppression accompanying infectious
      diseases, particularly AIDS, or in tumors.

PMID- 9257834
TI  - A solution to the rheumatoid factor paradox: pathologic rheumatoid factors can be
      tolerized by competition with natural rheumatoid factors.
AB  - Rheumatoid factors (RF) associated with arthritic joint erosion are only seen
      transiently, if at all, in nondiseased individuals. Therefore, a tolerance
      mechanism must exist that prevents pathologic RF B cells from expressing Abs.
      Surprisingly, it has been shown that pathologic RF B cells are not tolerized by
      any previously established tolerance mechanism such as deletion, receptor
      editing, anergy, or prevention of memory establishment. How are pathologic RF
      cells tolerized? By simulating the RF response with a cellular automaton model
      immune system, we demonstrate that pathologic RFs can be tolerized by the novel
      mechanism of "competitive tolerance" with natural, nonpathologic RFs. We then
      demonstrate that competitive tolerance can be broken when a sequestered pool of
      expanding B cells are inappropriately subjected to chronic stimulation (as
      appears to occur in MRL/lpr mice and in patients with rheumatoid arthritis).

PMID- 9257835
TI  - The requirement of intestinal bacterial flora for the development of an IgE
      production system fully susceptible to oral tolerance induction.
AB  - The role of intestinal bacterial flora in oral tolerance induction to the IgE
      response was investigated using germfree (GF) mice. When GF mice were orally
      administered 20 mg of OVA as tolerogen before a systemic challenge with OVA, the
      Th1-mediated responses, such as the production of IgG2a and IFN-gamma, were
      abrogated, while the Th2-mediated immune responses, such as the production of
      IgE, IgG1, and IL-4, were maintained. Moreover, the basal level of IL-4
      production in vitro was significantly higher in the GF mice than that of IL-4 in
      specific pathogen-free mice when challenged systemically with OVA. On the other
      hand, both Th1 and Th2 responses were fully sensitive to such tolerance induction
      in specific pathogen-free mice. The reconstitution of intestinal flora of GF mice
      with Bifidobacterium infantis, one of the predominant bacteria in the intestinal
      flora, restored the susceptibility of these Th2 responses to oral tolerance
      induction; however, this was only effective when such reconstitution was
      performed in neonates, but not in mice at an older age. These results thus
      suggested that intestinal bacterial flora play a crucial role in generating a Th2
      cell population whose size and response are adequately regulated and,
      consequently, fully susceptible to oral tolerance induction, probably by
      affecting the development of gut-associated lymphoid tissue at the neonatal
      stage.

PMID- 9257836
TI  - Homing of naive and memory T lymphocyte subsets to Peyer's patches, lymph nodes,
      and spleen.
AB  - The specificity and efficiency of extravasation of subsets of memory and naive
      lymphocytes into organized lymphoid tissues has been the subject of recent
      controversy, but has not been directly assessed in physiologic systems. Here, we
      compare the lymphoid organ homing of naive and phenotypically defined memory T
      cells, focusing on memory subsets differentially expressing the integrin receptor
      alpha4beta7, which is implicated in homing to mucosal sites. Naive T cells
      (CD44(low), Thy1+) home to all secondary lymphoid organs. Alpha4beta7(high)
      memory-phenotype (CD44(high)) T cells home to Peyer's patches as efficiently as
      naive lymphocytes, whereas alpha4beta7- memory-phenotype T cells are essentially
      excluded from entry into these mucosal lymphoid organs. In contrast, alpha4beta7-
      memory-phenotype cells home approximately twice as efficiently as
      alpha4beta7(high) T cells to peripheral lymph nodes, but only approximately 20%
      as well as naive T cells. Interestingly, the spleen recruits all three identified
      subsets with nearly equal efficiency. The relative subset localization is similar
      2.5 h after injection and after overnight trafficking, suggesting that memory
      cells can directly extravasate from blood into Peyer's Patches and lymph nodes.
      We conclude that subsets of memory T cells defined by patterns of homing receptor
      expression display differential homing to organized lymphoid tissues, an ability
      that may facilitate homeostatic interactions and target contributions to
      specialized regional immune responses.

PMID- 9257837
TI  - T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and
      their association with Lck.
AB  - Stimulation through the TCR is known to induce tyrosine phosphorylation of a
      number of proteins, which leads to functional activation of T cells.
      Identification of the substrates that become phosphorylated and defining their
      interactions with other signaling molecules will provide insight into the
      mechanisms controlling T cell activation. Focal adhesion kinase (FAK) and the
      recently described Pyk2 kinase are homologous members of a non-receptor protein
      tyrosine kinase family. FAK has been shown to become phosphorylated upon TCR
      stimulation, but its role, if any, in T cell activation remains to be defined.
      Although Pyk2 has been shown to play a role in neuronal cell activation
      stimulated through G-protein-coupled receptors, a role in T cell activation has
      not been described. In this study we show that FAK and Pyk2 are two of the major
      115-to-120-kDa proteins that become tyrosine phosphorylated in T cells following
      TCR complex stimulation. Furthermore, coincident with the increase in tyrosine
      phosphorylation, we show an association of these kinases with the SH2 domain of
      the tyrosine kinase Lck in vivo. The increase in tyrosine phosphorylation of both
      FAK and Pyk2, however, occurs in Lck-deficient cells suggesting that
      phosphorylation of both of these kinases does not require Lck. Taken together,
      these results suggest that FAK and Pyk2, perhaps in coordination with Lck, play a
      role in T cell activation.

PMID- 9257838
TI  - T cell antigen receptor-induced IL-2 production and apoptosis have different
      requirements for Lck activities.
AB  - The T cell hybridoma BI-141 has been previously used to dissect the roles of Lck
      in Ag-induced IL-2 production. Here we demonstrate that BI-141 undergoes
      apoptosis in response to TCR stimulation using Ag or anti-TCR Abs. Using a panel
      of BI-141 transfectants expressing constitutively activated Lck (F505) or
      phosphotyrosine-binding (K154F505 and C156F505) or kinase-impaired (R273F505)
      mutants, we assess the relative requirements for Lck in TCR-mediated IL-2
      production and apoptosis. While BI-141 transfectants expressing F505 are
      dramatically enhanced in their ability to produce IL-2 in response to Ag relative
      to K154F505-, C156F505-, or R273F505-expressing transfectants, no differences
      between these transfectants are observed in their ability to undergo TCR-induced
      apoptosis. TCR-induced Fas ligand (FasL) expression is demonstrated to be
      dependent on Lck SH2 and kinase activities, although FasL expression cannot be
      correlated with apoptosis. Low levels of Fas are constitutively expressed at
      equal levels on transfectants and are not increased in response to TCR ligation.
      Together, these data indicate that TCR-induced apoptosis in BI-141 is regulated
      through a mechanism(s) distinct from the Lck-induced expression of Fas, FasL, or
      IL-2 production. This TCR signal may be independent of Lck kinase and SH2
      activities, or may require lower threshold activity. The identification of
      differential requirements for particular T cell functions is crucial to
      understanding how TCR engagement affects downstream T cell functions and may aid
      in the rational design of therapeutics aimed at specifically modulating
      particular T cell responses.

PMID- 9257839
TI  - T cell genetic background determines maintenance of IL-12 signaling: effects on
      BALB/c and B10.D2 T helper cell type 1 phenotype development.
AB  - In this report, we examined the molecular basis underlying the genetic difference
      between BALB/c and B10.D2 T cells for T helper phenotype development in vitro. We
      found a strain-dependent difference in early maintenance of IL-12 responsiveness
      by T cells developing in vitro in unmanipulated (neutral) conditions. Thus, when
      activated without addition of exogenous cytokines or neutralization of endogenous
      cytokines, B10.D2, but not BALB/c, T cells remain responsive to IL-12 when
      activated for 7 days. The pattern of IL-12 responsiveness correlated with
      expression of the IL-12R signaling subunit, IL-12R beta2, and with IL-12-induced
      STAT4 phosphorylation. When activated under neutral conditions, BALB/c T cells
      rapidly lose IL-12R beta2 expression, STAT4 phosphorylation, and functional IL-12
      responsiveness. More efficient maintenance of IL-12R beta2 expression by B10.D2 T
      cells activated under neutral conditions may explain the previously observed
      increase in IFN-gamma production relative to that of BALB/c. This difference
      could potentially provide greater protection from certain pathogens that do not
      immediately elicit strong Th1-inducing conditions via activation of the innate
      immune system.

PMID- 9257841
TI  - Induction of germinal center B cell markers in vitro by activated CD4+ T
      lymphocytes: the role of CD40 ligand, soluble factors, and B cell antigen
      receptor cross-linking.
AB  - Following primary immunization, B cells differentiate to memory cells with help
      from T cells. The specialized path to B cell memory takes place in lymphoid
      germinal centers (GC), where mouse B cells up-regulate peanut agglutinin receptor
      (PNA-R), B7-2 (CD86), and MHC class II expression. Using an in vitro culture
      system, we have studied how different stimuli can enhance the expression of these
      markers. We show that PNA-R is up-regulated when splenic B cells are cocultured
      with anti-CD3-stimulated CD4+, but not CD8+, T cells and that this process
      requires CD40-CD40 ligand engagement. Increased expression of PNA-R is also
      inducible with supernatants of activated CD4+, but not CD8+, T cells in
      combination with mitogenic signals, such as anti-Ig, anti-CD40, or LPS, but not
      by either supernatants or mitogenic signals alone. Unlike with PNA-R, increased
      expression of B7-2 and I-A occurs in response to activated T cells of either CD4+
      and CD8+ subsets or their supernatants, does not require CD40 costimulation, and
      is readily induced with mitogenic signals alone. Taken together, these results
      indicate that PNA-R up-regulation has more restricted signaling requirements than
      B7-2 or I-A, and that it can be induced/maintained by Ag receptor cross-linking
      or CD40 engagement, as long as there is an appropriate cytokine milieu.

PMID- 9257842
TI  - Self gamma2a(b) protein is presented in vivo by gamma2a(b) B cells but not by
      dendritic cells.
AB  - We have previously shown that IgG2a(b) Ig does not induce tolerance in MHC class
      II restricted CD4 T cells in a TCR transgenic model and that anti-IgG2a(b)
      transgenic T cells specific for peptide 435-451 are indeed present in the
      periphery where they interact with gamma2a(b)-positive B cells. We also observed
      that because T cell tolerance depends on the presentation of self peptides, it
      was probable that IgG2a(b) was not easily processed and presented in vivo. In
      this study, we have investigated the presentation of naturally processed
      gamma2a(b) (435-451) determinants to specific T cells. Dendritic cells,
      macrophages, and B cells were purified from the spleens of Igh-1b mice. These
      cells were then functionally tested for the presence of specific peptide-MHC
      complexes. The results showed that, in vivo, gamma2a(b)-producing B cells, but
      not dendritic cells, are the only APCs able to present this self peptide. This
      indicates that recognition of the IgG2a(b)-self peptide is exclusively mediated
      by T-B cell interaction.

PMID- 9257840
TI  - TCR expression in human fetal intestine and identification of an early T cell
      receptor beta-chain transcript.
AB  - TCR expression by human fetal intestinal intraepithelial lymphocytes (ilELs) and
      intestinal lamina propria lymphocytes was analyzed to address whether T cell
      development occurs in human fetal intestine, the diversity of human fetal iIELs,
      and whether human fetal iIELs may contribute to the adult iIEL repertoire. ilELs
      and intestinal lamina propria lymphocytes from second trimester human fetal
      intestine were analyzed for TCR-alphabeta transcripts. Rearranged TCR-alpha
      transcripts were undetectable at 14 wk in the intraepithelial lymphocytes (IELs),
      whereas multiple TCR-beta transcripts were found at this stage. The TCR-alpha
      repertoire remained restricted relative to TCR-beta at later stages, and the IEL
      repertoire was restricted relative to the lamina propria lymphocytes at all
      stages. A previously reported T early alpha message was the major transcript from
      the TCR-alpha locus early in gestation. A previously undescribed TCR-beta
      transcript initiating upstream of the Dbeta1 locus and spliced to Cbeta1 or
      Cbeta2 was also identified and may represent a T early beta message. These
      results provide evidence for ongoing TCR gene rearrangement in human fetal
      intestine and suggest that transcription from the TCR-beta locus initiates with a
      T early beta transcript. The TCR-alpha repertoire (and hence the repertoire of
      potentially functional IELs) was limited through the second trimester.

PMID- 9257844
TI  - B cell responses to a peptide epitope: IV. Subtle sequence changes in flanking
      residues modulate immunogenicity.
AB  - We examined modulation of primary humoral responses to a model synthetic peptide
      immunogen, peptide PS1CT3, as a consequence of single amino acid substitutions.
      Two analogues were employed, one in which the amino-terminal histidine (His1,
      peptide G28CT3) and another in which an internal proline (Pro14, peptide G41CT3)
      were replaced with glycine residues. Peptide G28CT3 displayed markedly enhanced
      immunogenicity relative to peptide PS1CT3 in BALB/c mice, whereas peptide G41CT3
      was only poorly immunogenic. Nevertheless, in all three cases the mature
      polyclonal IgG response was predominantly directed against a tetrapeptide segment
      of sequence Asp-Pro-Ala-Phe between positions 4 and 7 of the sequence. While all
      three peptides proved equally capable of priming Ag-specific Th cells, they,
      however, displayed significant differences in their abilities to recall T cell
      responses. Regardless of the priming immunogen, in vitro challenge with either
      PS1CT3 or its analogues consistently gave a hierarchy of potencies as G28CT3 >
      PS1CT3 > G41CT3. This could also be correlated with B cell recall responses in
      which an identical hierarchy was obtained on restimulation of G41CT3-primed B
      cells in adoptive transfer experiments. Subsequent studies revealed that peptide
      mediated modulation of Th cell recruitment by Ag-primed B cells was probably due
      to differences in on-rates for engagement of B cell Ag receptor by these
      analogues. This was despite the fact that all three peptides displayed equally
      randomized conformations in solution. These studies indicate that even subtle
      variations in the flanking sequences can markedly influence the immunogenicity of
      B cell epitopes.

PMID- 9257843
TI  - Differential interaction of nuclear factors with the leukocyte-specific pp52
      promoter in B and T cells.
AB  - The leukocyte-specific, cytoskeleton-binding pp52 (LSP-1, WP-34) protein is
      widely expressed in multiple leukocyte lineages, including B and T lymphocytes,
      granulocytes, and macrophages. We previously detected a tissue-specific promoter
      preceding the exon encoding the N terminus of the pp52 leukocyte protein. Here we
      describe the functional characterization of this promoter and identification of
      the factors in B and T cells that regulate its activity. The pp52 promoter
      contains an initiator specifying the unique 5' terminus of pp52 mRNA, tandem
      pairs of Ets and SP1 motifs, and a lone C/EBP motif. All these motifs are
      essential and collectively control transcriptional activity. DNA binding studies
      and Ab supershift assays revealed that different combinations of factors interact
      with these motifs in B cells vs T cells. The Ets motifs are preferentially bound
      by PU-1 in B cell extracts from all stages of development, whereas a different
      Ets family member reacts with these motifs in T cell extracts. The C/EBP motif is
      bound by Ig/EBP-1 in pre-B cell and T cell extracts, but is replaced by nuclear
      factor-IL-6beta or a nuclear factor-IL-6beta-Ig/EBP-1 heterodimer in plasmacytoma
      cell extracts. Despite its reported role as a negative regulator of
      transcription, Ig/EBP-1 appears to exert a stimulatory effect on this promoter.
      These findings reveal the features controlling the pp52 promoter in B and T cells
      and provide the foundation for determining the regulation of this promoter in
      other leukocyte lineages.

PMID- 9257845
TI  - Salmonella typhimurium infections in mice deficient in interleukin-4 production:
      role of IL-4 in infection-associated pathology.
AB  - Mice harboring mutations in the IL-4 gene (IL-4(-/-)) were infected with a range
      of Salmonella typhimurium HWSH derivatives using different routes of infection.
      Compared with IL-4(+/+) mice, IL-4(-/-) mice exhibited a delayed time to death
      following infection with wild-type S. typhimurium HWSH. Groups of IL-4(+/+) mice
      infected with S. typhimurium HWSH purE, a less virulent derivative, showed
      sporadic deaths and harbored micro- or macroabscesses in their tissues,
      particularly associated with the liver. However, IL-4(-/-) mice infected with
      similar doses of S. typhimurium HWSH purE bacteria were resistant to killing and
      failed to develop detectable abscesses. Abscess formation in IL-4(-/-) mice could
      be induced by i.v. administration of rIL-4 during the S. typhimurium HWSH purE
      infection. The immune response in both IL-4(-/-) and IL-4(+/+) mice was of the
      Th1-type. Viable salmonella bacteria could be found associated with abscesses.
      Both IL-4(-/-) and IL-4(+/+) mice were resistant to killing by S. typhimurium
      aroA.

PMID- 9257846
TI  - Presentation via the class I pathway by Leishmania amazonensis-infected
      macrophages of an endogenous leishmanial antigen to CD8+ T cells.
AB  - CD8+ T cells play a protective role in immunity to cutaneous leishmaniasis.
      However, it has been unclear how these cells execute this function, since results
      from several investigations attempting to demonstrate recognition of Leishmania
      infected macrophages by CD8+ T cells have been contradictory. In this study, we
      report the generation of CD8+ T cell lines specific for GP46/M-2, a leishmanial
      Ag, previously shown to protectively immunize mice against a Leishmania
      amazonensis challenge. Using T cell cytolysis and IFN-gamma production to assess
      CD8+ T cell activation, we show that in addition to recognizing mammalian cells
      transfected with GP46/M-2, these CD8+ T cell lines also recognize macrophages
      infected with Leishmania amazonensis. MHC class I presentation of GP46/M-2 by
      infected macrophages can be blocked by treatment with brefeldin A and also by
      inhibitors of the cytosolic multicatalytic proteasome, N-acetyl-L-leucinyl-L
      leucinal-L-norleucinal and N-acetyl-L-leucinyl-L-leucinylmethional. These results
      suggest that this leishmanial Ag is processed in the macrophage cytoplasm and is
      presented to CD8+ T cells via the classical pathway of MHC class I presentation.
      The relevance of these findings as they impact on our understanding of the
      biology of the parasite within the macrophage is discussed.

PMID- 9257847
TI  - Congenic mapping of the insulin-dependent diabetes (Idd) gene, Idd10, localizes
      two genes mediating the Idd10 effect and eliminates the candidate Fcgr1.
AB  - The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is
      under the control of multiple insulin-dependent diabetes (Idd) genes. The Idd3
      gene, originally defined as a broad peak of linkage on mouse chromosome 3, was
      subsequently identified as two genes, Idd3 and Idd10, separated by at least 20
      cM. The resistance alleles of Idd3 and Idd10 individually confer only partial
      protection from diabetes but, in combination, result in profound resistance to
      disease due to an epistatic genetic interaction. In this study, we used newly
      developed congenic strains to further localize Idd10. Surprisingly, we found that
      Idd10 itself comprises at least two linked loci: Idd10 and the newly designated
      Idd17. Idd17 was localized to a 1.1-cM region between D3Mit26 and D3Mit40,
      proximal to Fcgr1, a candidate gene encoding the high affinity Fc receptor for
      IgG. Idd10 was localized to a 10-cM region between D3Mit213 and D3Mit106, distal
      to Fcgr1. Thus, Fcgr1 was excluded as a candidate for either Idd10 or Idd17,
      despite the fact that the NOD strain expresses a mutant form of the receptor.
      Interestingly, although Idd10 and Idd17 participate in a genetic interaction with
      each other, Idd10 but not Idd17 participates in the genetic interaction with
      Idd3. Our study on chromosome 3 begins to reveal the extent of the polygenic
      nature of autoimmune diabetes, and demonstrates that the use of congenic strains
      is an effective mapping strategy, even in the dissection of multiple, linked
      genes with subtle effects.

PMID- 9257849
TI  - Yersinia invasin, a bacterial beta1-integrin ligand, is a potent inducer of
      lymphocyte motility and migration to collagen type IV and fibronectin.
AB  - The Yersinia pseudotuberculosis invasin protein was found to be a potent inducer
      of pseudopodia formation and chemotactic and haptotactic migration in human T
      lymphocytes. Checkerboard analysis confirmed that migration was directional. The
      Yersinia invasin triggered migration of otherwise poorly migratory normal T cells
      on fibronectin and in particular on collagen type IV, and augmented the migration
      of leukemic T cell lines on these components. Invasin-induced lymphocyte
      migration was inhibited by staurosporin that selectively prevented pseudopodia
      formation but, noteworthy, augmented adhesion. The motogenic and attractant
      properties of invasin (Inv) were mediated via beta1-integrins, as shown by lack
      of effect of Inv on the motility of a beta1-integrin-negative lymphoid cell line
      and inhibition of invasin-induced lymphocyte motility by anti-beta1 Abs. Inv was
      markedly more effective than the extracellular matrix components fibronectin,
      collagen type IV, and laminin, which also interact with lymphocyte beta1
      integrins, with respect to induction of pseudopodia, chemotaxis, and haptotaxis.
      Thus, Yersinia invasin is a model ligand for induction of lymphocyte motility via
      beta1-integrins. The extraordinary capacity of Inv to trigger and guide T
      lymphocyte motility and potentiate lymphocyte migration to extracellular matrix
      components may be of pathogenetic significance for the movement of lymphocytes to
      extraintestinal sites secondary to Yersinia infection.

PMID- 9257848
TI  - Cytotoxic CD8+ T cells recognize EBV antigen but poorly kill autologous EBV
      infected B lymphoblasts: immunodominance is elicited by a peptide epitope that is
      presented at low levels in vitro.
AB  - CD8+ T cells play a crucial role in surveillance against EBV-associated
      malignancies. EBV-specific T cells traditionally have been identified by their
      ability to kill autologous EBV-transformed B lymphoblastoid cell lines (LCL).
      Here we report CD8+ cloned and bulk T cells that specifically recognize EBV
      nuclear Ag EBNA-3C, but do not efficiently kill autologous or HLA-matched LCL.
      The low cytolysis of these T cells was due to the extremely low density of the
      antigenic epitope (LDFVRFMGV, EBNA-3C amino acids 285-293) on autologous LCL. The
      T cells efficiently killed target cells in the presence of < 1 pM synthetic EBNA
      3C peptide and, therefore, recognize peptide/HLA complexes with high avidity.
      Donor T cells with this phenotype were stimulated by autologous LCL and dominated
      the in vitro EBV-specific response. This indicates that low abundance viral
      peptides can induce a dominant T cell response.

PMID- 9257851
TI  - Fc epsilonRI-deficient mice infected with Schistosoma mansoni mount normal Th2
      type responses while displaying enhanced liver pathology.
AB  - The IgE/Fc epsilonRI interaction is postulated to play an important role in
      resistance to helminths both at the level of anti-parasitic effector cell
      function and in the initiation of Th2 responses through IL-4 produced by Fc
      epsilonRI+ non-B, non-T (NBNT) cells. To formally evaluate the role of IgE/Fc
      epsilonRI signaling in the host response to helminths we studied Schistosoma
      mansoni infection in Fc epsilonRI knockout (KO) mice. Infected wild-type (wt) and
      KO animals showed comparable adult worm and tissue egg burdens, arguing against a
      role for Fc epsilonRI interactions in host resistance. Significantly, NBNT cells
      from infected KO, in contrast to wt animals, did not secrete IL-4 when stimulated
      with anti-IgE Ab or soluble parasite Ag. Nevertheless, serum IgE levels and Th2
      cytokine production profiles were comparable in both strains of mice,
      demonstrating that the Ag-dependent stimulation of IL-4 secretion by NBNT cells
      is not essential for helminth-induced Th2 differentiation. However, when
      stimulated with low Ag doses, splenocytes from infected Fc epsilonRI-deficient
      mice produced less IL-4 in vitro than similar cultures from infected wt animals,
      an effect attributable to their defective NBNT cell function. Moreover, infected
      KO mice showed enhanced egg granuloma formation and hepatic fibrosis, revealing
      that the IgE/Fc epsilonRI interaction, while not essential for Th2 response
      development or resistance to primary infection, plays a significant role in down
      regulating host pathology.

PMID- 9257852
TI  - Virus dissemination through the brain parenchyma without immunologic control.
AB  - After inoculation into the cerebrospinal fluid, the neurovirulent influenza virus
      A/WSN caused a rapidly progressive encephalitis that was uniformly fatal within 8
      days. After inoculation into the brain parenchyma, the same virus replicated for
      7 to 20 days without causing clinical illness, but when infection reached the
      cerebrospinal fluid, encephalitis was lethal within a further 6 days. As the
      virus spread through the brain parenchyma, there was intense intracerebral
      inflammation, with up-regulation of MHC class I and MHC class II expression and
      recruitment of CD44(high) CD49d(high) T cells. However, this was not associated
      with antiviral Ab production, and the infiltrating cells, unlike primed A/WSN
      specific T cells, did not eliminate the virus in vivo or show evidence of virus
      recognition in vitro. Thus, a neurovirulent virus was able to disseminate widely
      through the brain parenchyma and induce considerable intracerebral inflammation
      without eliciting protective immunity.

PMID- 9257850
TI  - Biologic activity of proteoglycan macrophage colony-stimulating factor.
AB  - We compared the biologic activities of 85-kDa macrophage-CSF (85-kDa M-CSF),
      which is fully active, and a proteoglycan M-CSF (PG-M-CSF). Both originate from
      the same precursor, but the latter retains the carboxyl-terminal portion, which
      must be proteolytically removed from the precursor to generate 85-kDa M-CSF and
      which is uniquely modified by a chondroitin sulfate glycosaminoglycan chain. PG-M
      CSF supported the formation of murine macrophage colonies such as 85-kDa M-CSF.
      Furthermore, PG-M-CSF stimulated the proliferation of murine bone marrow
      macrophages, an M-CSF-dependent murine cell line, and an M-CSF-responsive human
      cell line established by transfer of the human M-CSF receptor gene. PG-M-CSF and
      85-kDa M-CSF had equivalent specific biologic activities on a molar basis in all
      bioassays. The activity of PG-M-CSF was not affected by enzymatically removing
      the glycosaminoglycan chain when assayed by the formation of macrophage colonies
      and proliferation of the bone marrow macrophages. We analyzed the phosphorylation
      on tyrosine residue(s) of the M-CSF receptor in response to these M-CSFs that
      trigger mitogenic responses. PG-M-CSF rapidly (within 10 min) induced receptor
      phosphorylation in human cells with the same potency as 85-kDa M-CSF. These
      results indicate that PG-M-CSF is not a latent form or precursor of 85-kDa M-CSF
      but a fully biologically active cytokine.

PMID- 9257853
TI  - DNA vaccines against lymphoma: promotion of anti-idiotypic antibody responses
      induced by single chain Fv genes by fusion to tetanus toxin fragment C.
AB  - Idiotypic determinants can act as tumor-associated Ags for B cell lymphoma.
      Vaccination with idiotypic protein and adjuvant is known to induce specific
      protection against lymphoma challenge in mice, largely mediated by anti-idiotypic
      Ab. For facilitating the approach for patients, the V(H) and V(L) genes used to
      encode the individual idiotypic determinants of each tumor can be obtained by PCR
      and assembled as single chain Fv (scFv). DNA vaccines containing scFv sequences
      alone induce low and poorly reproducible levels of anti-idiotypic Ab, likely to
      be insufficient to suppress tumor in patients. In addition, it may be necessary
      to break tolerance to Id in tumor bearers. By fusing the gene for fragment C of
      tetanus toxin to the C terminus of human scFv, we have promoted the anti-scFv Ab
      response in mice by >50-fold in three of three cases. The induced Abs are mainly
      against idiotypic determinants, and react specifically with patients' tumor
      cells, indicating optimal folding of the scFv molecule in the fusion protein. For
      both antigenic components of the DNA vaccine, the IgG subclass distribution
      showed a relative increase in IgG2a as compared with vaccination with IgM protein
      in adjuvant. In patients, the fusion gene should both promote anti-idiotypic Ab
      and induce Abs against fragment C of tetanus toxin. The latter response would
      provide a potentially useful comparative measure of the ability of patients to
      respond to conventional Ag delivered via DNA.

PMID- 9257854
TI  - Matching antibody class with pathogen type and portal of entry: cognate
      mechanisms regulate local isotype expression patterns in lymph nodes draining the
      respiratory tract of mice inoculated with respiratory viruses, according to virus
      replication competence and site of inoculation.
AB  - Intranasal deposition of Sendai virus (SV) in C57BL/6 mice provokes an Ab-forming
      cell (AFC) reaction in mediastinal (MLN) and cervical lymph nodes (CLN), which
      drain the lungs and upper respiratory tract, respectively. While the majority of
      AFC elicited by infectious SV at both sites produced IgG, the CLN response to SV
      rendered inactive in replication was restricted almost entirely to IgA, although
      isotype switching in mediastinal continued to be skewed heavily to IgG. However,
      in vitro restimulation of the accompanying virus-specific T cell populations from
      the two sites did not reveal any significant difference in lymphokine output, and
      isotype expression was not altered substantially in mice lacking IL-4 or IL-6
      genes. To dissociate the response to specific Ags from the inflammatory reaction
      to viral infection, we examined the response to inactivated SV in the face of
      infection with influenza virus A/HKx31. The magnitude and IgA dominance of the
      anti-SV AFC population in the CLN were unaffected by a simultaneous, vigorous,
      IgG-dominated CLN anti-influenza reaction. Evidently, the characteristics of this
      antiviral response are determined primarily by cognate interactions. Moreover,
      the IgA bias of the CLN AFC response to inactivated SV was observed only when the
      virus was delivered intranasally: injection under the epidermis of the cheek, a
      site that has a lymphatic drainage into the CLN, resulted in an IgG-dominated CLN
      AFC reaction, lacking IgA. The site of deposition of a vaccine can thus have more
      influence on the pattern of isotypes induced than the site at which the immune
      response is initiated.

PMID- 9257855
TI  - Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma
      gondii.
AB  - Resistance of perforin knockout (PKO) mice to infection with Toxoplasma gondii
      was assessed in models of acute infection and during chronic disease. PKO mice
      vaccinated with the attenuated mutant, ts-4, displayed severely defective CTL
      responses against tachyzoite-infected targets. Lysis of the NK target, YAC-1, was
      also severely impaired in PKO mice following ts-4 vaccination. In contrast, wild
      type mice developed high levels of CTL and NK lytic activity after ts-4
      vaccination. Despite severely defective lytic activity, vaccinated PKO animals
      were completely resistant to challenge with the virulent strain RH, which
      normally causes a lethal acute infection. Resistance was attributable to
      production of IFN-gamma, which remained unimpaired in the PKO animals. In
      contrast, when PKO mice were infected with low virulence parasite strain ME49,
      which progresses to the cyst-forming stage after passage through an acute phase,
      accelerated mortality was observed beginning at 75 days postinfection. A three-
      to fourfold increase in brain cyst numbers was also found by day 30 in infected
      PKO animals. Nevertheless, the PKO strain produced normal levels of IFN-gamma
      after ME49 infection, ruling out impaired production of the latter cytokine as a
      cause of increased susceptibility. Together, these results show that perforin
      dependent cytolytic function is not required for host resistance to lethal acute
      infection in preimmunized animals, but that the latter activity contributes to
      the control of infection during the chronic stage.

PMID- 9257856
TI  - Human endothelial cell activation and mediator release in response to the
      bacterial exotoxins Escherichia coli hemolysin and staphylococcal alpha-toxin.
AB  - Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin are
      membrane-perturbating bacterial exotoxins that have been implicated as
      significant virulence factors in human diseases. We investigated the capacity of
      these toxins to cause cell activation and mediator release in human endothelial
      cells, compared with the efficacies of thrombin and the Ca2+ ionophore A23187.
      Concentration ranges tested were 1 to 1000 ng/ml (HlyA), 0.01 to 10 micro/ml
      (alpha-toxin), 0.01 to 10 U/ml (thrombin), and 0.01 to 10 microM (A23187). All
      stimuli caused dose-dependent generation of platelet-activating factor, nitric
      oxide, and prostaglandin I2. HlyA and thrombin effected time- and dose-dependent
      accumulation of large quantities of inositol phosphates, with maximum effects at
      100 ng/ml and 1 U/ml, respectively. Corresponding time course and dose dependency
      were noted for HlyA-elicited diacylglycerol formation. In contrast, only the
      highest concentrations of alpha-toxin (10 microg/ml) and A23187 (10 microM)
      effected some moderate inositol phosphate accumulation, and this was suppressed
      in the presence of the platelet-activating factor antagonist WEB 2086. Metabolic
      and secretory responses elicited by alpha-toxin were dependent on the presence of
      extracellular Ca2+. We conclude that both HlyA and alpha-toxin are potent
      inductors of inflammatory and vasodilatory mediators in human endothelial cells.
      HlyA-elicited effects may proceed predominantly via activation of the
      phosphatidylinositol hydrolysis-related signal transduction pathway, whereas
      transmembrane Ca2+ flux appears to be the major event underlying the release of
      mediators in response to alpha-toxin. These toxin properties may contribute to
      vasoregulatory and inflammatory disturbances encountered in states of severe
      infection and sepsis.

PMID- 9257857
TI  - Expression of leukocyte fucosyltransferases regulates binding to E-selectin:
      relationship to previously implicated carbohydrate epitopes.
AB  - E-selectin is a carbohydrate-binding endothelial cell adhesion molecule that
      reportedly interacts with several related sialylated and fucosylated
      carbohydrates. The activity of leukocyte alpha1,3-fucosyltransferases (FucT-IV or
      FucT-VII) is an essential step in the synthesis of E-selectin ligands. Using a
      panel of stably transfected hemopoietic cell lines, we have investigated the role
      of alpha1,3-fucosyltransferases in generating E-selectin ligands, and the
      relationship between adhesion to E-selectin and expression of mAb-defined
      carbohydrates. Expression of FucT-VII was always sufficient for binding to E- and
      P-selectin, while the ability of FucT-IV to construct E-selectin ligands varied
      among different cell types. Furthermore, FucT-IV was unable to support any
      binding to P-selectin in a lymphoid cell line, even when expressed at levels
      equivalent to those in myeloid cells. FucT-IV expression generated high levels of
      surface Le(x)/CD15 and CDw65, whereas expression of FucT-VII correlated with a
      subset of mAb-defined sialyl Lewis X (sLex)-like structures. FucT-IV-associated
      epitopes were present on both binding and nonbinding cells, whereas all cells
      that expressed FucT-VII-associated epitopes bound E-selectin. However, treatment
      of HL60 cells with neuraminidase destroyed FucT-VII-associated epitopes at a
      faster rate than E-selectin binding sites. Surface expression of a subset of mAb
      defined sLex-like carbohydrates is therefore a good marker for high levels of
      FucT-VII activity, but these carbohydrates are not themselves required for
      recognition of E-selectin.

PMID- 9257858
TI  - Human dermal microvascular endothelial cells express the melanocortin receptor
      type 1 and produce increased levels of IL-8 upon stimulation with alpha
      melanocyte-stimulating hormone.
AB  - Pro-opiomelanocortin (POMC)-derived peptides such as alpha-melanocyte-stimulating
      hormone (alpha-MSH) recently have been recognized as mediators with potent
      immunomodulating and anti-inflammatory properties. Their effects are mediated via
      different protein G-coupled melanocortin (MC) receptors that are capable to bind
      one or more POMC-derived peptides. Among these receptors, MC-1 is specific for
      alpha-MSH and adrenocorticotropin. The purpose of the present study was to
      investigate whether MC receptors are expressed on normal human dermal
      microvascular endothelial cells (HDMEC) as well as transformed human dermal
      microvascular endothelial cells (HMEC-1). Using semiquantitative reverse
      transcriptase-PCR and MC receptor-specific primers, both HDMEC and HMEC-1 were
      found to express MC-1 constitutively. In addition, MC-1 expression was increased
      upon stimulation with IL-1beta or alpha-MSH itself. Other known MC receptors were
      neither detectable in unstimulated nor in IL-1beta- or alpha-MSH-stimulated
      cells. The binding of alpha-MSH by HMEC-1 was specific and saturable as
      demonstrated by competitive and saturation-binding studies with 125I-labeled
      alpha-MSH (Kd: 1.1 nM). To evaluate the physiologic relevance of MC-1 expression,
      HMEC-1 were treated with various concentrations of alpha-MSH (10(-15)-10(-6) M)
      and were investigated for their cytokine-producing capacity. Alpha-MSH (10(-10)
      10(-8) M) significantly up-regulated IL-8 release and mRNA expression by HMEC-1.
      In contrast, the production of IL-1 or IL-6 by HMEC-1 was not affected upon
      treatment with alpha-MSH. These data provide first evidence that HDMEC express
      functional MC receptors. Therefore, alpha-MSH, which is released in the skin
      during cutaneous inflammation via inducing chemokines may represent an important
      signal required for leukocyte-endothelial cell interaction.

PMID- 9257859
TI  - Induction of ceruloplasmin synthesis by IFN-gamma in human monocytic cells.
AB  - Ceruloplasmin is a 132-kDa glycoprotein abundant in human plasma. It has multiple
      in vitro activities, including copper transport, lipid pro- and antioxidant
      activity, and oxidation of ferrous ion and aromatic amines; however, its
      physiologic role is uncertain. Although ceruloplasmin is synthesized primarily by
      the liver in adult humans, production by cells of monocytic origin has been
      reported. We here show that IFN-gamma is a potent inducer of ceruloplasmin
      synthesis by monocytic cells. Activation of human monoblastic leukemia U937 cells
      with IFN-gamma increased the production of ceruloplasmin by at least 20-fold. The
      identity of the protein was confirmed by plasmin fingerprinting. IFN-gamma also
      increased ceruloplasmin mRNA. Induction followed a 2- to 4-h lag and was
      partially blocked by cycloheximide, indicating a requirement for newly
      synthesized factors. Ceruloplasmin induction in monocytic cells was agonist
      specific, as IL-1, IL-4, IL-6, IFN-alpha, IFN-beta, TNF-alpha, and LPS were
      completely ineffective. The induction was also cell type specific, as IFN-gamma
      did not induce ceruloplasmin synthesis in endothelial or smooth muscle cells. In
      contrast, IFN-gamma was stimulatory in other monocytic cells, including THP-1
      cells and human peripheral blood monocytes, and also in HepG2 cells.
      Ceruloplasmin secreted by IFN-gamma-stimulated U937 cells had ferroxidase
      activity and was, in fact, the only secreted protein with this activity.
      Monocytic cell-derived ceruloplasmin may contribute to defense responses via its
      ferroxidase activity, which may drive iron homeostasis in a direction unfavorable
      to invasive organisms.

PMID- 9257860
TI  - Suppression of ongoing ocular inflammatory disease by topical administration of
      plasmid DNA encoding IL-10.
AB  - Ocular infection with herpes simplex virus leads to an inflammatory lesion in the
      cornea orchestrated by CD4+ Th1 lymphocytes. This immunopathologic disease,
      called herpetic stromal keratitis, is an important cause of impaired vision. In
      this study, we set out to determine whether established lesions of herpetic
      stromal keratitis could be controlled by topically administering naked plasmid
      DNA encoding cytokines to the corneal surface. A single topical administration of
      DNA encoding IL-10 was beneficial to the majority (75%) of treated animals, and
      50% (vs 10% in controls) resolved their lesions completely over a 23-day
      observation period. Topical ocular application of DNA encoding foreign proteins
      was also shown to be an effective means of inducing systemic and mucosal immune
      responses. The direct application of DNA encoding cytokines may represent an
      additional therapeutic option for the management of immunoinflammatory disease.

PMID- 9257861
TI  - Potentiation of C1 inhibitor by glycosaminoglycans: dextran sulfate species are
      effective inhibitors of in vitro complement activation in plasma.
AB  - Activation of the complement system may contribute to the pathogenesis of many
      diseases. Hence, an effective inhibitor of complement might be useful to reduce
      tissue damage. Some glycosaminoglycans (GAG), such as heparin, are known to
      inhibit the interaction of C1q with activators and the assembly of the classical
      and the alternative pathway C3 convertases. Furthermore, they may potentiate C1
      inhibitor-mediated inactivation of C1s. To search for potential complement
      inhibitors, we systematically investigated the complement inhibitory properties
      of various synthetic and naturally occurring GAG (dextran sulfates 500,000 and
      5,000, heparin, N-acetylheparin, heparan sulfate, dermatan sulfate, and
      chondroitin sulfates A and C). First, we assessed the effect of GAG on the second
      order rate constant of the inactivation of C1s by C1 inhibitor. This rate
      constant increased 6- to 130-fold in the presence of the GAG, dextran sulfate
      being the most effective. Second, all tested GAG were found to reduce deposition
      of C4 and C3 on immobilized aggregated human IgG (AHG) and to reduce fluid phase
      formation of C4b/c and C3b/c in recalcified plasma upon incubation with AHG.
      Dextran sulfate again was found to be most effective. We conclude that GAG
      modulate complement activation in vitro and that the low molecular weight dextran
      sulfate (m.w. 5000) may be a candidate for pharmacologic manipulation of
      complement activation via potentiation of C1 inhibitor.

PMID- 9257863
TI  - Listeria monocytogenes potently induces up-regulation of endothelial adhesion
      molecules and neutrophil adhesion to cultured human endothelial cells.
AB  - Infection of endothelial cells by Listeria monocytogenes is an essential step in
      the pathogenesis of listeriosis. Listeriolysin (Hly) is one of its major
      virulence factors. In the early phase of the disease polymorphonuclear leukocytes
      (PMN) substantially contribute to the nonspecific anti-listerial resistance. We
      characterized the effects of L. monocytogenes on the expression of endothelial
      adhesion molecules and on subsequent PMN adhesion to cultured HUVEC. P-selectin,
      E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell
      adhesion molecule-1 (VCAM-1) were up-regulated in HUVEC after cell incubation
      with L. monocytogenes (wild type), but not with the nonpathogenic Listeria
      innocua strain. P-selectin expression peaked after 30 min and could be mimicked
      with similar kinetics by exposure to L. innocua engineered to produce large
      amounts of Hly or by addition of purified Hly. Listeriolysin production, however,
      was not necessary for an up-regulation of E-selectin after 6 h or of ICAM-1 and
      VCAM-1 after 18 to 24 h in HUVEC, because L. monocytogenes defective for Hly
      synthesis was almost as effective as the wild type. Listeria-induced up
      regulation of endothelial adhesion molecules was accompanied by an increased
      binding of PMN to infected HUVEC. PMN adhesion was significantly reduced in the
      presence of anti-beta2 integrin, anti-E-selectin, and anti-ICAM-1, but not anti
      VCAM-1 Abs. Our data indicate that infection of endothelial cells with L.
      monocytogenes induced up-regulation of adhesion molecules by two different
      mechanisms: a Hly-dependent up-regulation of P-selectin and a Hly-independent
      expression of E-selectin, ICAM-1, and VCAM-1. The ability of L. monocytogenes to
      stimulate PMN adhesion to endothelial cells may be an important mechanism in the
      pathogenesis of severe listeriosis.

PMID- 9257862
TI  - Thrombopoietin promotes adhesion of primitive human hemopoietic cells to
      fibronectin and vascular cell adhesion molecule-1: role of activation of very
      late antigen (VLA)-4 and VLA-5.
AB  - Thrombopoietin (Tpo), the ligand for c-mpl and a principal regulator of
      megakaryocytopoiesis and platelet production, has been demonstrated to stimulate
      the growth and differentiation of megakaryocyte as well as multipotent
      hemopoietic progenitor cells. In the present study we demonstrate that Tpo can
      stimulate the adhesion of the Mo7e progenitor cell line to fibronectin (Fn) as
      well as vascular cell adhesion molecule-1 through activation of very late antigen
      (VLA)-4 and VLA-5, adhesion molecules previously demonstrated to be involved in
      regulation of steady state hemopoiesis. Tpo-induced adhesion was concentration
      dependent, reached a maximum following 30 min, and appeared to be dependent on
      adenylate cyclase, and tyrosine kinase activity. Furthermore, second messenger
      inhibitors implicated essential and complimentary roles of phosphatidylinositol-3
      kinase and protein kinase C in mediating Tpo-induced adhesion. The ability of Tpo
      to promote adhesion to fibronectin was comparable to that of IL-3, but less than
      that of stem cell factor. Unlike the ability of these cytokines to
      synergistically enhance growth of Mo7e as well as normal progenitor cells, no
      synergy was observed with regard to their ability to enhance adhesion. Finally,
      Tpo stimulated adhesion of primitive (CD34+ CD38-) human bone marrow cells to
      fibronectin, predominantly through activation of VLA-5, whereas no such effect
      could be observed on CD34+ CD38+ bone marrow cells. Thus, Tpo might play an
      important role in early hemopoiesis, at least in part through its ability to
      promote adhesion through activation of adhesion molecules on hemopoietic
      progenitor cells.

PMID- 9257864
TI  - P- and L-selectin mediate distinct but overlapping functions in endotoxin-induced
      leukocyte-endothelial interactions in the rat mesenteric microcirculation.
AB  - Endotoxin is a potent stimulus of leukocyte infiltration, but the adhesion
      related mechanisms responsible for LPS-induced cell recruitment events in vivo
      remain poorly characterized. Utilizing intravital microscopy, we examined the
      role of P- and L-selectin in LPS-induced inflammation. We demonstrated that
      superfusion of rat mesentery with LPS resulted in significant increases in both
      leukocyte rolling and adherence, which were maintained for at least 2 h.
      Pretreatment with a P-selectin neutralizing mAb only partially inhibited LPS
      induced leukocyte rolling, but completely inhibited LPS-induced leukocyte
      adherence throughout the 2-h observation period. Pretreatment with an L-selectin
      neutralizing mAb dramatically inhibited LPS-induced increases in leukocyte
      rolling, but unlike the P-selectin mAb did not inhibit leukocyte adhesion.
      Fucoidin, which blocks both P- and L-selectin function, completely inhibited LPS
      induced leukocyte rolling and adhesion. Consistent with previous studies,
      leukocyte rolling velocities on P-selectin were observed to be far less than
      velocities observed for leukocytes rolling on L-selectin in vivo. These data
      suggest that P-selectin plays a role in LPS-induced rolling and is essential for
      LPS-induced leukocyte adherence, while L-selectin functions in LPS-induced
      rolling, but not in adhesion.

PMID- 9257865
TI  - Selective conversion of big endothelins to tracheal smooth muscle-constricting 31
      amino acid-length endothelins by chymase from human mast cells.
AB  - Chymase from human mast cells selectively cleaved big endothelins (ETs) at the
      Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length
      endothelins, ETs(1-31), without any further degradation products. Chymases from
      other species, such as the enzymes from rat connective tissue and mucosal mast
      cells, and the other chymotrypsin-like proteases examined degraded big ETs. ETs(1
      31) exhibited various contractile potencies as to the rat trachea in comparison
      with 21-amino acid-length endothelins, ETs(1-21), and big ETs: ET-1(1-21) > ET
      1(1-31) > big ET-1; ET-2(1-31) > ET-2(1-21) > or = big ET-2; ET-3(1-21) > or = ET
      3(1-31) > or = big ET-3. Among the ETs(1-31), ET-2(1-31) was the most potent
      constrictor, its potency being similar to that of ET-1(1-21) and stronger than
      that of ET-2(1-21). The contractile activity of ETs(1-31) may not be the
      consequence of conversion to the corresponding ETs(1-21) by phosphoramidon
      sensitive ET-converting enzymes or other chymotrypsin-type proteases and
      metalloendopeptidases, because the contractile activity was not inhibited
      significantly on treatment with inhibitors of these proteases before the addition
      of ET-1(1-31). Inhibitors of chymotrypsin-type serine proteases, on the contrary,
      significantly enhanced the contractile activity exhibited by ET-1(1-31) and big
      ET-1, but not that by ET-1(1-21). These results suggest that protease(s) on the
      surface of the rat trachea tends to degrade ETs(1-31) and big ETs, and thereby
      reduces their contractile activity. Taken together, the results suggest that
      trachea-constricting ETs(1-31) generated by human chymase may play a role in the
      hyper-responsive airway in allergic inflammation.

PMID- 9257866
TI  - Receptor expression and responsiveness of human dendritic cells to a defined set
      of CC and CXC chemokines.
AB  - Dendritic cells (DC) are migratory cells that exhibit complex trafficking
      properties in vivo. The present study was designed to characterize receptor
      expression and responsiveness to chemoattractants of human DC obtained from PBMC
      by culture with granulocyte/macrophage-CSF and IL-13. DC expressed appreciable
      levels of the CCR1, CCR2, and CCR5 receptors for the CC chemokines and the
      chemokine receptors CXCR1, CXCR2, and CXCR4. DC increased intracellular free
      calcium and migrated in response to the CC chemokines MCP-3, MCP-4, RANTES, MIP
      1alpha, MIP-1beta, and MIP-5/HCC2 and the CXC chemokine SDF-1. In contrast, the
      CC chemokines MCP-1 and eotaxin had little or no activity in the concentration
      range tested (up to 1 microg/ml). IL-8 and Gro-beta (CXC) and lymphotactin (C
      chemokines) were also inactive. DC did not respond to 5-HETE, whereas platelet
      activating factor was an active agonist. Selected chemokines active on DC in
      terms of migration and calcium fluxes were examined for their capacity to
      modulate endocytosis and Ag presentation. Under conditions in which TNF-alpha was
      active, MCP-1, MCP-3, MIP-1alpha, and RANTES did not affect these two responses.
      Thus, among hemopoietic elements, DC respond to a unique set of CC and CXC
      chemokines, and their responsiveness is restricted to migration with no effect on
      Ag capture and presentation. Chemokines may play a role in the trafficking of DC
      under resting or stimulated conditions. Chemokine receptors expressed in DC are
      likely to underlie HIV infection of this cell type.

PMID- 9257867
TI  - Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B
      virus transgenic mice.
AB  - The pathogenetic effector functions of hepatitis B virus (HBV)-specific CD4+, Th1
      cells were analyzed in two inbred lineages of HBV transgenic mice, one of which
      overexpresses the HBV large envelope protein rendering the hepatocytes
      hypersensitive to the cytopathic effects of IFN-gamma, and another that expresses
      all of the HBV proteins and replicates the virus in the liver. Transfer of HBV
      envelope-specific Th1 cells resulted in recognition of viral Ag expressed by
      hepatic nonparenchymal cells, cytokine release, and a transient necroinflammatory
      liver disease in both lineages. The liver disease was very severe in the IFN
      gamma-sensitive lineage, and it was less severe in the lineage that replicates
      the HBV genome; nonetheless, in this lineage the Th1 cytokines produced by these
      cells suppressed viral replication in the liver. These results demonstrate that
      CD4+ T cells with a Th1 functional phenotype can perform pathogenetic and
      antiviral effector functions in vivo. This suggests that CD4+ T cells can
      contribute directly to disease pathogenesis and inhibit viral replication during
      HBV infection.

PMID- 9257868
TI  - Characterization of autoantibodies in pemphigus using antigen-specific enzyme
      linked immunosorbent assays with baculovirus-expressed recombinant desmogleins.
AB  - Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune skin diseases
      caused by autoantibodies against desmoglein (Dsg) 3 and Dsg1, respectively.
      Routine immunofluorescence testing of skin and serum from patients cannot
      distinguish between these two severe diseases since both have IgG Abs directed
      against keratinocyte cell surfaces. In this study, recombinant Dsg3 and Dsg1,
      produced as secreted proteins by baculovirus expression, have been utilized to
      develop ELISAs for the specific characterization of their autoantibodies. Of 49
      PV sera, 46 were positive in the Dsg3 ELISA and 44 of 46 PF sera were positive in
      the Dsg1 ELISA, compared with only 3 of 23 sera of bullous pemphigoid, and none
      of 53 normal control sera in both ELISAs. Both the Dsg3 and Dsg1 ELISAs were more
      specific and sensitive than conventional immunofluorescence staining. These Ag
      specific ELISAs revealed that more than one-half of PV sera (26 of 49) had anti
      Dsg1 Abs in addition to anti-Dsg3 Abs. PV patients who had not only oral mucous
      lesions but also significant skin involvement tended to have higher titers of
      anti-Dsg1 Abs. Furthermore, the ELISA reactivity correlated well with clinical
      disease activity in 5 of 6 PV and 5 of 5 PF patients. This ELISA provides a
      sensitive and highly specific assay for the diagnosis of patients with PV and PF,
      the correlation of disease activity with serum Ab levels, and a novel tool for
      investigating the immunopathogenesis of pemphigus.

PMID- 9257869
TI  - Human T cell leukemia virus type I (HTLV-I)-specific CD8+ CTL clones from
      patients with HTLV-I-associated neurologic disease secrete proinflammatory
      cytokines, chemokines, and matrix metalloproteinase.
AB  - Human T cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) is a chronic, progressive neurologic disease
      characterized by marked degeneration of the spinal cord and the presence of
      infiltrating CD8+ T cells and macrophages. HAM/TSP patients have very high
      frequencies of HTLV-I-specific CD8+ CTL in peripheral blood and in cerebrospinal
      fluid. In this study, we show that HAM/TSP patients also have elevated levels of
      peripheral blood CD8+ T cells that produce intracellular IFN-gamma. To address
      the potential role of soluble mediators secreted by CD8+ T cells in the
      pathogenesis of HAM/TSP, we have analyzed the capacity of a panel of nine HTLV-I
      specific CD8+ CTL clones derived from three HAM/TSP patients to secrete
      cytokines, chemokines, and matrix metalloproteinases. The results demonstrate
      that the majority of these CTL clones secrete IFN-gamma, TNF-alpha, macrophage
      inflammatory protein-1alpha and -1beta, IL-16, and matrix metalloproteinase-9.
      These findings indicate that HTLV-I-specific CD8+ CTL are an important source of
      proinflammatory soluble mediators that may contribute significantly to the
      pathogenesis of HAM/TSP.

PMID- 9257870
TI  - Allergenic properties of ovomucoid in man.
AB  - Ovomucoid, the dominant allergen in hen's egg, is a highly glycosylated protein
      comprising 186 amino acids arranged in three tandem domains (Gal d 1.1, 1.2, and
      1.3). The purpose of this study was to evaluate the allergenic properties of
      ovomucoid. The three ovomucoid domains were isolated and evaluated with sera from
      egg allergic patients to determine B cell domain specificity, B cell epitopes,
      and the relative importance of linear and conformational structures and
      carbohydrate chains to B cell epitopes. Peripheral blood T cells from egg
      allergic patients were used to evaluate T-dominant domains and reactivity to
      reduced and oxidized ovomucoid. There was significantly more IgE activity to the
      second ovomucoid domain (median percentage of ovomucoid-specific IgE: Gal d 1.2,
      40%; Gal d 1.1, 23%; Gal d 1.3, 26%). Quantities of patient IgG Ab were
      comparable for all three domains. Five IgE and seven IgG binding regions were
      identified. IgE Ab binding to reduced ovomucoid and IgG binding to oxidized
      ovomucoid were significantly reduced compared with that to native ovomucoid (28
      and 69%, respectively). Peripheral blood T cells of 21 of 33 patients reacted to
      Gal d 1.3, 18 of 33 reacted to Gal d 1.2, and 18 of 33 reacted to Gal d 1.1. T
      cell proliferation in vitro in response to reduced and oxidized ovomucoid were
      significantly greater than that in response to the native protein. These results
      indicate a dichotomy between T and B cell domain dominance, and the presence of
      both unique and common IgE and IgG epitopes. Furthermore, the results suggest
      that conformational B cell epitopes play a more significant role in ovomucoid
      allergenicity than previously appreciated, and that carbohydrate moieties have a
      minor effect on allergenicity.

PMID- 9257872
TI  - Accumulation of human T lymphotropic virus (HTLV)-I-specific T cell clones in
      HTLV-I-associated myelopathy/tropical spastic paraparesis patients.
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraperesis (HAM/TSP) is a slowly progressive neurologic disorder following
      infection with HTLV-I. It is characterized by spasticity and hyper-reflexia of
      the lower extremities, urinary bladder disturbance, lower extremity muscle
      weakness, and sensory disturbances. HTLV-I, as an inducer of a strong humoral and
      cytotoxic response, is a well-known pathogenic factor for the progression of
      HAM/TSP. Peptides derived from proviral tax and env genes provide epitopes
      recognized by T cells. We herein report an accumulation of distinct clonotypes of
      alpha/beta TCR+ peripheral blood T lymphocytes from HAM/TSP patients in
      comparison with that observed in both asymptomatic carriers and healthy controls,
      using the reverse-transcriptase PCR/single-strand conformation polymorphism
      method. We also found that some of the accumulated T cell clones in the
      peripheral blood and cerebrospinal fluid are HTLV-I Tax(11-19) peptide specific.
      Such clones were found to expand strongly after being cultured with an HTLV-I
      Tax(11-19) peptide. Moreover, the cultured samples exhibited a strong MHC class I
      restricted cytotoxic activity against HTLV-I Tax(11-19) peptide-expressing
      targets, and therefore most likely also include the disease-associated T cell
      clones observed in the patients. This is the first report of a direct assessment
      of Ag-specific T cell responses in fresh PBL and cerebrospinal fluid.

PMID- 9257871
TI  - Autoantibodies to ribosomal P proteins penetrate into live hepatocytes and cause
      cellular dysfunction in culture.
AB  - Abs to ribosomal P protein have been shown to bind a membrane form of the P0 38
      kDa ribosomal phosphoprotein. This study shows that after affinity-purified Abs
      to ribosomal P proteins bind living HepG2 cells, they then penetrate these live
      cells and cause cellular dysfunction. Binding and penetration of anti-P Abs is
      the property of F(ab')2 fragments as well as whole IgG molecules showing that
      neither binding nor penetration depends on Fc fragments or their cognate
      receptors. Confocal microscopy shows that internalized Ab concentrates in
      perinuclear vesicles (presumably lysosomes), but substantial quantities of Ab are
      also found in the cytosol. This intracellular Ab adversely affects the synthesis
      of apolipoprotein B resulting in a threefold increase in cellular cholesterol
      with lipid droplet accumulation as seen in some chronic liver diseases. It also
      has a profound inhibitory effect on global protein synthesis as measured by
      [35S]methionine incorporation. These studies therefore describe a model of
      cellular injury effected by specific Ab to ribosomal "P" protein that may
      underlie certain forms of autoimmune hepatic diseases.

PMID- 9257873
TI  - HIV-1 envelope-specific CD4+ T helper cells from simian/human immunodeficiency
      virus-infected rhesus monkeys recognize epitopes restricted by MHC class II
      DRB1*0406 and DRB*W201 molecules.
AB  - The HIV-1 envelope (Env)-specific Th cell response of rhesus monkeys infected
      with nonpathogenic chimeric simian/human immunodeficiency viruses (SHIV) was
      assessed at a molecular level by establishing rgp120-specific CD4+ T cell lines.
      Epitopes recognized by these MHC class II-restricted Th cells were identified
      within the second (C2), third (C3), and fifth (C5) conserved regions of HIV-1
      gp120. The epitope located in C2 was found to be restricted by the rhesus monkey
      (Macaca mulatta) leukocyte Ag Mamu-DRB1*0406, and the Th cell epitope in C5 was
      found to be restricted by Mamu-DRB*W201. The restriction element requirements of
      the C2 and C5 epitope-specific CD4+ Th cells appear to be rather stringent,
      because these peptide epitopes were not recognized in the presence of other Mamu
      DR expressing cell lines. The ability to analyze HIV-1 Env-specific CD4+ T cell
      responses in SHIV-infected monkeys will enhance the utility of this model for
      studying AIDS pathogenesis and for assessing novel HIV-1 vaccine strategies.

PMID- 9257875
TI  - Plasma tissue factor and tissue factor pathway inhibitor levels in patients with
      disseminated intravascular coagulation.
AB  - We measured the plasma levels of tissue factor (TF) and tissue factor pathway
      inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to
      examine the relationship between TFPI and vascular endothelial cell injury.
      Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were
      significantly increased in patients with DIC compared with non-DIC patients.
      Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/-
      85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly
      increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC
      patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy
      volunteers (0.84 +/- 0.26). There was no significant difference between the DIC
      patients with a good outcome and those with a poor outcome in terms of plasma TF
      levels, although the plasma TFPI level in the DIC patients with a good outcome
      (289 +/- 133 ng/ml) was significantly higher than those with a poor outcome (187
      +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased
      first, and an increase of the plasma TFPI level followed the increase in plasma
      TF level. These findings suggest that plasma TFPI is released from vascular
      endothelial cells and it may reflect vascular endothelial cell injury. It is
      conceivable that TF and TFPI may play an important role in the onset of DIC.

PMID- 9257874
TI  - Intercellular adhesion molecule-1 deficiency protects MRL/MpJ-Fas(lpr) mice from
      early lethality.
AB  - MRL/MpJ-Fas(lpr) (Fas(lpr)) mice develop a rapidly fatal form of systemic
      autoimmune disease characterized by glomerulonephritis and vasculitis similar to
      severe cases of systemic lupus erythematosus in humans. To evaluate the
      requirement for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of
      tissue injury in this model, we created ICAM-1-deficient MRL/MpJ-Fas(lpr) (ICAM
      1/Fas(lpr)) mice. ICAM-1 deficiency resulted in a striking improvement in the
      survival of Fas(lpr) mice (median +/- SEM survival of Fas(lpr) = 26 +/- 1.7 vs
      ICAM-1/Fas(lpr) = 47 +/- 2.4 wk, p < 0.0001) and the increased survival was
      associated with delayed elevations of blood urea nitrogen levels in the ICAM
      1/Fas(lpr) mice. Histologic examination of the ICAM-1/Fas(lpr) mice revealed an
      overall reduction in glomerular disease and a significant reduction in vasculitis
      in the kidney, lung, skin, and salivary glands when compared with Fas(lpr). These
      findings indicate that ICAM-1 plays a major role in development of glomerular and
      vascular injury in Fas(lpr) mice.

PMID- 9257876
TI  - Morphological variants of leukemic cells in B chronic lymphocytic leukemia are
      associated with different T cell and NK cell abnormalities.
AB  - B chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease. The different
      morphological variants of leukemic B cells appear to define different clinical
      groups of patients. Several abnormalities have been found in T lymphocytes and
      natural killer (NK) cells from B-CLL patients. We have investigated the
      phenotypic and functional characteristics of purified CD2+ cells from B-CLL
      patients at Binet's stage A and classified according to the neoplastic B
      lymphocyte morphology criteria: 32 patients with typical B-CLL and 12 patients
      with atypical B-CLL. Forty-three age and sex matched healthy controls were also
      studied. In fresh purified CD2+ cells from typical B-CLL patients, percentages of
      CD4+, CD4+CD45RA+, CD8+CD45RA+ T lymphocytes and CD3-CD56+ (NK) cells were
      significantly higher than those found in atypical B-CLL patients. However, in
      DC2+ cells from typical B-CLL patients, percentages of CD3+, CD3+DR+, CD8+,
      CD4+CD45RO+, and CD3+CD56+ cells were significantly lower than those found in
      atypical B-CLL patients. Increased percentage of NK cells was only found in
      typical B-CLL patients. The proliferative response and the production of
      interleukin (IL)-2 and IL-4 by phytohemagglutinin (PHA) stimulated CD2+ cells
      were significantly higher in typical B-CLL patients than in atypical B-CLL
      patients. We concluded that different patterns of phenotypic and functional
      alterations in the T lymphocytes and NK cells of B-CLL patients are found in
      patients with typical or atypical B-CLL defined according to the morphology of
      the leukemic cells.

PMID- 9257878
TI  - Cancer incidence rate and mortality rate in sickle cell disease patients at
      Howard University Hospital: 1986-1995.
AB  - The incidence of cancer in patients with sickle cell disease (SCD) is not known.
      The 10-year follow-up data on 696 patients with SCD was analyzed at our
      institution in order to determine the cancer incidence and cancer mortality
      rates. The age range was 18 to 79 years, with a mean age of 28.8 years. There
      were 377 females and 319 males. The median follow-up was 3 years. Five patients
      developed cancer during this period. The cancer incidence rate was 5/2,864 or
      1.74 per 1,000 patient years. The 95% CI was 0.64 to 4.32 per 1,000 patient
      years. There were 68 deaths with 3 being due to cancer. The cancer mortality rate
      was 3/2,873 or 1.04 cases per 1,000 patient years. Our data represent the first
      published paper that the authors are aware of, where the cancer incidence and
      mortality rates have been calculated for any group of patients with SCD.

PMID- 9257879
TI  - Plasma tissue factor antigen levels in capillary whole blood and venous blood:
      effect of tissue factor on prothrombin time.
AB  - To measure the amount of tissue factor released during specimen collection and
      its potential effect of shortening the prothrombin time, we measured tissue
      factor and prothrombin time in twenty-three paired venous and capillary blood
      samples from anticoagulated patients and in ten paired samples from controls. We
      also compared venous prothrombin time determined by a plasma-based assay with
      venous and capillary prothrombin time determined with a whole blood assay. Venous
      specimens were obtained using a two-syringe technique; capillary specimens were
      obtained by fingerstick after wiping the first drop of blood. Plasma tissue
      factor was determined by an enzyme-linked immunoabsorbant assay. The patients'
      mean venous tissue factor (235 +/- 101 pg/ml) and capillary tissue factor (268 +/
      106 pg/ml) were higher than those of the controls (161 +/- 42 pg/ml and 187 +/-
      63 pg/ml, respectively, P < 0.05). These differences disappeared after adjusting
      for age. Capillary tissue factor levels were higher than venous tissue factor
      (244 +/- 102 pg/ml vs. 213 +/- 93 pg/ml), with a mean difference of 31 pg/ml (P =
      0.0001). In addition, whole blood prothrombin time was lower in the capillary
      than in the venous samples (17.7 +/- 5 sec vs. 18.3 +/- 5.4 sec, P = 0.004).
      However, there was no correlation between capillary-venous differences in tissue
      factor and capillary-venous differences in the whole blood prothrombin time.
      Whole blood capillary and venous prothrombin times highly correlated with the
      plasma-based venous prothrombin time (r = 0.98, P < 0.0001). These results
      demonstrate that obtaining blood by fingerstick does not result in a clinically
      significant release of tissue factor. In addition, we did not observe any
      interference of plasma tissue factor with the whole blood prothrombin time assay.
      A direct relationship between tissue factor and age was observed.

PMID- 9257877
TI  - Increased tissue factor pathway inhibitor in patients with acute myocardial
      infarction.
AB  - We examined hemostatic abnormalities in 23 patients with acute myocardial
      infarction (AMI), 10 with pulmonary embolism (PE), and 10 with deep vein
      thrombosis (DVT). At the onset of AMI, plasma levels of tissue-type plasminogen
      activator (t-PA), PA inhibitor-I (PAI-I), fibrin-D-dimer, thrombin-antithrombin
      complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly
      increased. Both the plasma total TFPI and free-TFPI levels in the AMI patients
      were significantly higher than those in the healthy volunteers, PE patients, and
      DVT patients. There was no significant difference in total TFPI or free-TFPI
      among patients with PE, those with DVT, and healthy volunteers. One hour after
      percutaneous transluminal coronary angioplasty (PTCA) in the AMI group, the total
      TFPI level was further increased, and it was significantly reduced 24 hr after
      PTCA, to a level similar to that in healthy volunteers. Free-TFPI showed a
      pattern similar to that of total TFPI. The ratio of free-TFPI/total TFPI was
      highest 1 hr after PTCA. Increased TFPI in AMI patients might be released from
      ischemic tissues.

PMID- 9257880
TI  - Feasibility, toxicity, and activity of LNH84-derived chemotherapy in the
      management of aggressive lymphomas.
AB  - The results of chemotherapy remain unsatisfactory for many patients with advanced
      lymphomas. Both standard and more aggressive chemotherapy regimens might have
      their respective role in the management of theses diseases. We have tested the
      feasibility and assessed the toxicity and activity of a LNH84-derived
      chemotherapy for aggressive non-Hodgkin's lymphoma in two general hospitals.
      Thirty-three untreated patients were included over a period of 4 years. Median
      age was 39 years, 21 were male. International Working Formulation was F for 2
      patients, G for 17, H for 8, I for 1, J for 4, one unclassified. Seventeen
      patients had B symptoms, 15 stage IV, 8 bulky disease, 21 abnormal LDH, 5
      performance status > or =2. The overall response rate was 93%. The single
      treatment related death resulted from bleomycin acute pneumonitis. Neutropenia
      WHO grade 4 occurred in all patients, resulting in infections grade 3 in 12 and
      thrombocytopenia grade 4 in 3. In the induction phase, courses could never be
      repeated day 14. The dose intensity of the four drugs contained in this phase is
      thus calculated between 64.5 and 81.5%. At 3 years, overall survival is 80% and
      event-free survival is 62%. This LNH84-derived regimen is effective. However, the
      induction phase is toxic and a 3-weekly interval appears more appropriate. Such
      intensive treatment might benefit patients with very aggressive lymphomas and
      this should be studied in randomized comparison against standard CHOP.

PMID- 9257881
TI  - Frequency of BCL-2/J(H) translocations in peripheral blood of follicular lymphoma
      patients.
AB  - Polymerase chain reaction (PCR) assays have been developed for follicular
      lymphoma-associated BCL-2/J(H) translocations. Few data are available on the
      quantitation by PCR of these translocations in peripheral blood mononuclear cells
      (PBM) of follicular lymphoma (FL) patients. We report that only one of five
      studied FL patients had a high level of these translocations in the circulation,
      namely, about 35,000 translocations per 5 x 10(6) PBM. This patient was stable
      with an excellent performance status at the time of this assay; however, he died
      of leukemia 1 month later.

PMID- 9257882
TI  - Previously undescribed form of B-cell chronic lymphoid leukemia with IgA
      expression/secretion and lytic bone lesions.
AB  - A B-cell chronic lymphoid leukemia (B-CLL) associated with IgA expression and
      secretion is uncommon and has never been described in association with osteolytic
      bone lesions. We report such a case, defined by cytomorphology and flow
      cytometric immunophenotyping (FCI). Additional cases may be recognized with the
      aid of FCI, in order to define the natural history of and best form of therapy
      for this rare disorder.

PMID- 9257883
TI  - Leukemic thyroiditis as the initial relapsing sign in a patient with acute
      lymphocytic leukemia and blast expression of the neural cell adhesion molecule.
AB  - We report a patient with a history of T-cell ALL in remission who presented with
      symptoms and laboratory values consistent with subacute thyroiditis but was found
      to have leukemic thyroiditis as the first clinical manifestation of leukemic
      relapse. Bone marrow examination at this time demonstrated recurrent ALL. After
      successful re-induction with chemotherapy and an allogeneic bone marrow
      transplant this patient developed an isolated recurrence of her ALL manifested by
      symptomatic thyromegaly and a new mediastinal mass that was treated with
      irradiation. Despite no medullary recurrence of ALL, the patient developed
      pleuritic chest pain and shortness of breath and succumbed to pericardial
      extramedullary leukemia 9 months later. This to our knowledge is the third
      reported case of symptomatic ALL involvement of the thyroid gland and the first
      to be confirmed histologically. Furthermore, this patient had blast expression of
      the neural cell adhesion molecule (CD56), a cell surface marker that has not been
      studied in ALL but has previously been identified as a risk factor for
      extramedullary leukemia (EML) in acute non-lymphocytic leukemia. The authors
      hypothesize that CD56 expression in this patient might have contributed to her
      predisposition to EML.

PMID- 9257884
TI  - Detection of the PEBP2beta/MYH11 fusion transcript in acute myelomonoblastic
      leukemia (M4Eo) supervening in a patient with adult T-cell leukemia.

PMID- 9257885
TI  - Effect of sublethal total body irradiation on acute graft-versus-host disease and
      graft-versus-leukemia effect in SCID mice.
AB  - SCID mice were transplanted with H-2-incompatible C3H/He splenocytes with or
      without previous TBI with 2Gy to evaluate the influence of sublethal TBI on GVHD
      and on the graft-versus-leukemia (GVL) effect. Transplantation immediately after
      TBI induced lethal GVHD, but delayed donor leukocyte infusion (DLI) 5 days after
      TBI reduced the severity of the GVHD. SCID mice inoculated with L1210 cells after
      TBI received a DLI 5 days after TBI to induce the GVL effect. Survival of these
      mice was longer than that of control nonirradiated mice. Serum levels of tumor
      necrosis factor-alpha, IL-1alpha, IL-6, IL-2 and IFN-gamma were significantly
      elevated, and they reached maximum levels at 5 days post-transplantation. Except
      for IFN-gamma, all cytokine levels were higher in irradiated mice than those in
      nonconditioned mice. Cytotoxicity against L1210 cells mediated by splenocytes
      from irradiated recipients was greater than that mediated by effector cells from
      nonirradiated mice. All the irradiated mice survived more than 120 days after
      L1210 rechallenge, while all nonirradiated mice died of leukemia within 5 weeks.
      In conclusion, compared with control mice infused with donor splenocytes without
      previous TBI, SCID mice which received sublethal TBI and DLI showed superior
      cytotoxicity against L1210 cells and survived longer without severe GVHD.

PMID- 9257886
TI  - Feasibility of a PB CD34+ cell transplantation procedure using standard
      leukapheresis products in very small children.
AB  - To evaluate the feasibility and efficacy of CD34+ cell immunoselection from
      routine peripheral blood stem cell (PBSC) harvests in very small children a
      prospective study was performed in 15 children with advanced neuroblastoma
      weighing 20 kg or less. Products of two consecutive leukaphereses carried out on
      a COBE Spectra separator after G-CSF alone mobilization were pooled for
      immunoselection on Ceprate column. The median number of CD34+ cells and total CFU
      GM collected were respectively 5.9 x 10(6)/kg (range 2.3-23.4) and 126.9 x
      10(4)/kg (range 52.9-559.9). After separation the median number of CD34+ cells in
      the adsorbed fraction was 2.6 x 10(6)/kg (range 1-9.8) with a median purity of
      54% (range 21-82) and a median of 95.7-fold (range 35-250) enrichment. Thirteen
      patients underwent autografts with CD34+ PBSCs after a busulfan 600 mg/m2 +
      melphalan 180 mg/m2 preparative regimen. The median number of days to achieve an
      absolute granulocyte count of 0.5 x 10(9)/l and a platelet count of 20 x 10(9)/l
      were respectively, 12 (range 10-24) and 35 (range 25-43). The median number of
      platelet transfusions was nine (range 2-15). We conclude that safe and effective
      immunoselection and transplantation of CD34+ PBSC can be accomplished in children
      with low body mass.

PMID- 9257887
TI  - High-dose sequential chemotherapy with stem cell support for non-metastatic
      breast cancer.
AB  - The importance of dose-intensity has been suggested in breast cancer. The aim of
      this study was to evaluate the feasibility of a high-dose intensity doxorubicin
      cyclophosphamide regimen with supporting G-CSF and blood stem cells. Twenty-five
      patients with non-metastatic breast cancer received four cycles of doxorubicin
      (75 mg/m2) and cyclophosphamide (3000 mg/m2) at 3 week intervals. Apheresis was
      performed after the first cycle and if necessary after the second cycle. Stem
      cells were reinfused after the third and fourth cycles. G-CSF was started on day
      3 of each cycle (5 microg/kg/day) and was stopped the day before the last
      apheresis or when absolute neutrophil count was above 0.5 x 10(9)/l. Median
      received dose-intensity was respectively 25 mg/m2/week (range 22-26) and 1000
      mg/m2/week (range 904-1065) for doxorubicin and cyclophosphamide. Grade IV
      thrombocytopenia occurred in 8% of cycles. Two patients needed platelets and 12
      red cell transfusion. Fifteen patients were readmitted for a median duration of 4
      days (range 1-7). We have established a safe, outpatient, high-dose intensity
      doxorubicin-cyclophosphamide regimen with supporting G-CSF and blood stem cells
      which can be submitted for comparison with the current standards.

PMID- 9257889
TI  - Comparison of peripheral blood progenitor cell mobilization in patients with
      multiple myeloma: high-dose cyclophosphamide plus GM-CSF vs G-CSF alone.
AB  - The best method for peripheral blood progenitor cell (PBPC) mobilization in
      patients with multiple myeloma (MM) remains controversial. We report the results
      of two different methods of PBPC collection for autologous transplantation in 40
      patients with stage II or III MM. In group I (n = 18), HD-CY, 4 g/m2 i.v., was
      administered followed by GM-CSF, 8 microg/kg/day s.c., until the end of
      collection, starting the leukaphereses after hematological recovery (>1 x 10(9)/l
      WBC). In group II (n = 22), G-CSF, 10 microg/kg/day s.c., was used alone until
      the last day of collection, starting consecutive aphereses on the 5th day. A
      minimum of two aphereses were performed to collect at least 2 x 10(6)/kg CD34+
      cells. Both patient groups were comparable for age, sex and clinical prognostic
      features as well as previous therapies. In group I, the median yields per
      pheresis were: MNC 1.47 (1.38-2.32) x 10(8)/kg, CFU-GM 0.82 (0.18-13.2) x
      10(4)/kg and CD34+ cells 1.98 (0.96-6.96) x 10(6)/kg. In group II these results
      were: MNC 2.44 (2.06-3.6 x 10(8)/kg) (P = 0.03), CFU-GM 0.75 (0.16-7.8) x
      10(4)/kg and CD34+ 1.05 (0.32-3.4) x 10(6)/kg (P = 0.02). The median number of
      aphereses performed in each group was 5 (4-12) with a median of 5.24 +/- 2.51 in
      group I and 3 (2-6) with a median of 3.1 (+/- 0.91) in group II (P = NS).
      Hospitalization for PBPC mobilization was required in all patients in group I and
      the treatment-related toxicity was greater in this group: 12 patients (66%)
      developed fever requiring antibiotics during the neutropenic period after HD-CY
      and six (33%) patients required transfusion support. After receiving busulfan 12
      mg/kg p.o. and melphalan 140 mg/m2 i.v., as the conditioning regimen, the median
      periods to reach granulocytes (>0.5 x 10(9)/l) and platelet (>20 x 10(9)/l)
      engraftment were 12 and 11 days respectively (ranges 8-20 and 10-16) in group I
      (HD-CY plus GM-CSF group), and 11 and 13 days respectively (ranges 7-42 and 10
      38) in group II (G-CSF group) (P = NS). In conclusion, these data suggest that
      although HD-CY plus GM-CSF is superior to G-CSF alone based on mean CD34+ cell
      yield per pheresis, adequate CD34+ cell collections can be achieved with G-CSF
      alone in most MM patients with less toxicity and with simplification of the
      procedure.

PMID- 9257888
TI  - Plasma cells in peripheral blood stem cell harvests from patients with multiple
      myeloma are predominantly polyclonal.
AB  - A flow cytometric technique has been developed to detect individual plasma cells
      in PBSC harvests and to establish light chain restriction as a surrogate marker
      of their clonality. Plasma cells were identified by high intensity CD38 (CD38++)
      and cytoplasmic immunoglobulin (cIg) expression. The ratio of cytoplasmic kappa
      to lambda expression was used to detect light chain restriction. All 25 PBSC
      harvests studied contained CD38++/cIg plasma cells (mean 0.7%, range 0.03-2%).
      Harvests from non-myeloma patients also contained plasma cells (mean 0.4%, range
      0.01-1.5%). Most of the plasma cells detected in the harvests from myeloma
      patients were immature (CD45+/CD45++) rather than mature (CD45-). When the total
      plasma cell population was studied, definite isotype restriction could be
      detected in only 16% of harvests. Light chain restriction was found in 53% of
      harvests when the mature plasma cells (CD45-) were analysed but only in 9% of
      harvests when immature (CD45+/CD45++) plasma cells were analysed. Five percent of
      patients with myeloma had detectable light chain restriction in peripheral blood
      CD19+ cells. There was concordance between the ratio of malignant (CD19-/CD56+)
      to normal (CD19+/CD56-) plasma cells and light chain expression in 86% of
      patients studied. This study has demonstrated that the majority of plasma cells
      in PBSC harvests from patients with myeloma are not only immature but are also
      predominantly polyclonal and that monoclonality is best detected in mature plasma
      cells.

PMID- 9257891
TI  - Elevated serum HLA class I levels coincide with acute and chronic graft-versus
      host disease.
AB  - The ability to predict the likely occurrence of graft-versus-host-disease (GVHD)
      after BMT would be extremely valuable. We performed a retrospective study on the
      correlation between soluble HLA class I (sHLA-I) levels and GVHD in the sera of
      34 patients receiving an allogeneic BMT and in the sera of 12 patients receiving
      an autologous BMT. sHLA-I levels measured pre- and at different times post-BMT
      were correlated with the occurrence of post-BMT complications, ie acute graft
      versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD),
      infections and relapse. No changes in sHLA-I levels (delta sHLA-I) occurred in
      autologous and allogeneic BMT patients without GVHD. In contrast, sHLA-I reached
      high levels in patients suffering from GVHD. Increased sHLA-I levels correlated
      strongly with episodes of both acute and chronic GVHD (P = 0.004 and P = 0.005,
      respectively). Also during relapse increased sHLA-I levels were found (P =
      0.032). During infections sHLA-I levels increased, although not significantly.
      Kinetic studies gave no evidence that the increase in sHLA-I levels preceded the
      clinical occurrence of aGVHD or of cGVHD. A slight, but significant correlation
      was found between total blood bilirubin levels and sHLA-I levels in patients
      suffering from GVHD (P = 0.037), indicating the contribution of the liver as a
      source of sHLA-I. We conclude that measurements of sHLA-I levels do not function
      as a predictive parameter for GVHD, but can be valuable for the monitoring of
      GVHD after BMT.

PMID- 9257890
TI  - Allogeneic bone marrow transplantation with matched unrelated donors for patients
      with hematologic malignancies using a preparative regimen of high-dose
      cyclophosphamide and fractionated total body irradiation.
AB  - Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor
      is effective therapy for patients with bone marrow failure states and those with
      hematologic malignancies. However, only a minority of them will have an HLA
      identical sibling donor; unrelated donors, matched or partially mismatched, have
      been used successfully for patients lacking a related donor. Even though results
      with allogeneic transplants using unrelated donors are encouraging, the incidence
      of complications including graft-versus-host disease (GVHD) and graft rejection
      or late graft failure is increased compared to identical sibling transplants. The
      combination of cyclophosphamide and total body irradiation (TBI) has been used as
      an effective preparative regimen for allogeneic transplants, however, the total
      dosage and dosing schedule of both the cyclophosphamide and TBI has varied
      significantly among studies. To decrease the rate of graft rejection and late
      graft failure with volunteer donors, we evaluated a preparative regimen of high
      dose cyclophosphamide (200 mg/kg over 4 consecutive days, days -8, -7, -6, -5)
      followed by fractionated TBI (1400 cGy administered in eight fractions over 4
      days, days -4, -3, -2, -1). GVHD prophylaxis included FK506 and methotrexate.
      From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18
      58 years), were treated with this preparative regimen. Seventeen patients had low
      risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were
      matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional
      pairs were minor mismatched at the HLA-A or HLA-B loci. Four other
      donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele
      mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid
      engraftment. Engraftment occurred in all 40 patients at a median of 19 days.
      There were no cases of graft rejection or late graft failure. Nephrotoxicity was
      the primary adverse event with 26 patients (60%) experiencing a doubling of their
      creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of
      whom had high-risk disease. All patients who had relapsed or refractory disease
      prior to BMT achieved a complete remission following BMT. Six patients
      transplanted for high-risk disease relapsed a median of 377 days post-BMT. None
      of the patients with low-risk disease have relapsed following transplant; the
      Kaplan-Meier survival for those patients with low-risk disease is 62% and 37% for
      those patients transplanted with high-risk disease (P = 0.0129). The median
      Karnofsky performance status is 100% (range 70-100%). Therefore, a preparative
      regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable
      regimen for patients receiving an allograft from unrelated donors.

PMID- 9257892
TI  - Persistent donor chimaerism is consistent with disease-free survival following
      BMT for chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia (CML) can be treated successfully with allogeneic bone
      marrow transplantation (BMT) leading to long-term disease-free survival. Leukemia
      relapse, however, remains a significant clinical problem. Relapse following BMT
      presumably results from the expansion of small numbers of recipient leukaemic
      cells which have survived the conditioning therapy. In order to define patients
      who are at a high risk of leukaemia relapse, a variety of techniques have been
      employed to detect persistence of host haemopoiesis (mixed chimaerism, MC) or
      residual leukaemia (minimal residual disease, MRD). However, the precise
      relationship between the detection of MC and MRD post-BMT is unknown. We have
      investigated chimaerism and MRD status in 22 patients who were in clinical and
      haematological remission post-allogeneic BMT for chronic phase CML. Chimaerism
      was assessed using short tandem repeat PCR (STR-PCR) while BCR-ABL mRNA detection
      using reverse transcriptase polymerase chain reaction (RT-PCR) was performed to
      detect the presence of MRD. Seventeen patients received unmanipulated marrow (non
      TCD) while in five patients a T cell-depleted transplant (TCD) was performed as
      additional GVHD prophylaxis. Chimaerism was evaluated in 18 patients (14 non-TCD,
      four TCD). Mixed chimaerism was an uncommon finding in recipients of
      unmanipulated BMT (21%) when compared to TCD BMT (100%). No evidence of MRD, as
      identified using the BCR-ABL mRNA RT-PCR assay, was detected in those patients
      who were donor chimaeras. Early and transient MC and MRD was detected in four
      patients (two non-TCD, two TCD) who have subsequently converted to a donor
      profile. One patient has stable low-level MC but remains MRD negative 4 years
      post-BMT. Late MC and MRD was observed in two patients who relapsed >6 years
      after TCD BMT for CML. We conclude that mixed chimaerism is a rare event in
      recipients of unmanipulated BMT and that donor chimaerism as detected by STR-PCR
      assay is consistent with disease-free survival and identifies patients with a low
      risk of leukaemic relapse post-BMT for CML.

PMID- 9257894
TI  - Allogeneic bone marrow transplantation for Alexander's disease.
AB  - In this case report, we evaluate the efficacy of allogeneic bone marrow
      transplantation (BMT) in a 7-month-old female with the infantile form of
      Alexander's disease. Based on research that describes Alexander's disease as a
      leukodystrophy which may result from an unidentified enzyme deficiency, we
      attempted marrow transplantation to reverse or arrest the patient's neurological
      deterioration. Despite an initial return to her pretransplant neurological state,
      the patient's neurological status deteriorated. Marrow transplantation was not
      effective in changing her prognosis with Alexander's disease.

PMID- 9257893
TI  - Cyclosporine-induced retinal toxic blindness.
AB  - We report the case of a BMT recipient who developed blindness 22 months after
      BMT. Microvascular retinopathy, cortical blindness and other ocular pathologies
      were excluded with appropriate tests. Electrophysiological studies showed retinal
      damage without excluding an optic nerve lesion. The patient, who had several risk
      factors for neurologic-induced cyclosporine toxicity, improved with cyclosporine
      withdrawal. Our findings stress the need of electrophysiological tests to exclude
      neuroretinal damage in patients receiving cyclosporine after BMT.

PMID- 9257895
TI  - Spontaneous regression of relapsed non-Hodgkin's lymphoma in a patient who
      received an autologous transplant for primary resistant disease.
AB  - Poor prognosis malignant lymphoma is often treated with autologous bone marrow
      transplantation. Relapse after transplantation is usually associated with disease
      progression and resistance to further therapy. We present a case in which a 50
      year-old patient relapsed with multiple pulmonary metastases shortly after
      peripheral blood stem cell transplantation. Remarkably, this relapse remitted
      spontaneously. This may provide valuable insights into tumour cell biology and
      mechanisms by which stem cell mobilisation may alter this.

PMID- 9257896
TI  - Cyclosporin A-induced ocular flutter after marrow transplantation.
AB  - Ocular flutter is a rare neurologic condition occurring in patients suffering
      from viral encephalitis, intracranial neoplasia, paraneoplastic syndrome or
      intoxications. Neurotoxicity is a recognized complication of cyclosporin A (CsA)
      therapy, but ocular flutter has not been reported in association with CsA
      administration to date. We describe a 17-year-old female patient who developed
      ocular flutter 51 days after transplantation with marrow from an unrelated donor,
      for acute myeloid leukemia. After discontinuation of cyclosporin, which was given
      for prophylaxis of graft-versus-host disease, the clinical symptoms resolved
      within 3 weeks, but a slightly abnormal electrooculogram persisted for more than
      10 months.

PMID- 9257897
TI  - Tacrolimus (FK506) in allogeneic bone marrow transplantation for severe aplastic
      anemia following orthotopic liver transplantation.
AB  - Severe aplastic anemia (SAA) is a frequent complication of orthotopic liver
      transplantation for non-typeable viral hepatitis. Allogeneic bone marrow
      transplantation (BMT) may successfully reconstitute hematopoiesis but the optimal
      conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in such
      patients are unknown. Allogeneic BMT was undertaken in an 8-year-old male patient
      who developed SAA 6 weeks after cadaveric orthotopic liver transplantation for
      fulminant hepatic failure secondary to presumed non-typeable viral hepatitis. The
      preparative regimen for his HLA genotypically identical sibling BMT consisted of
      cytoxan and anti-thymocyte globulin. Tacrolimus (FK506) and prednisone, used to
      prevent liver graft rejection, were supplemented with methotrexate on post-BMT
      days, 1, 3, 6 and 11 for GVHD prophylaxis. Engraftment proceeded promptly and
      without complications. Transfusion dependence resolved 6 weeks after BMT. The
      patient is alive and well 1 year after his BMT on FK506 and prednisone without
      any signs of GVHD or liver allograft rejection. This case is the first
      demonstration of the feasibility of continuing FK506 used for prevention of liver
      graft rejection as GVHD prophylaxis for allogeneic BMT.

PMID- 9257898
TI  - Microangiopathy without hemolysis in a patient following allogeneic bone marrow
      transplantation.
AB  - Thrombotic microangiopathy (TMA) is one of the complications of bone marrow
      transplantation (BMT) which includes hemolytic uremic syndrome (HUS) and
      thrombotic thrombocytopenic purpura (TTP). Red cell fragmentation is the most
      consistent laboratory finding. We present a case of TMA with endothelial damage
      but without the signs of hemolysis. The patient was not receiving cyclosporine.
      Partial activation of platelets was also observed. This case represents a new
      form of TMA in transplant recipients.

PMID- 9257899
TI  - Inducible nitric oxide synthase after sensitization and allergen challenge of
      Brown Norway rat lung.
AB  - 1. We studied the effects of ovalbumin (OA) sensitization and challenge on
      inducible nitric oxide synthase (iNOS) gene and protein expression in Brown
      Norway rats in vivo. 2. By use of Northern analysis, a 4.4-kb iNOS mRNA
      transcript was weakly observed in control rat lung but there was a 3 fold
      increase in lungs sensitized to OA alone (P<0.05). In sensitized rats, four hours
      after exposure to OA aerosol, there was a 6 fold increase in iNOS mRNA transcript
      (P<0.05), which returned to baseline at 24 h. 3. Immunostaining with an anti
      mouse iNOS antibody revealed some patchy staining of airway epithelium in naive
      rats. There were no changes in sensitized rats exposed to saline, but sensitized
      and OA-exposed rats showed increased expression in iNOS staining in macrophages.
      4. Electrophoretic mobility shift assays of lung nuclear extracts showed a marked
      increase in nuclear factor-kappaB (NF-kappaB)-binding activity at 2 h after
      allergen exposure with return to baseline at 6, 12 and 24 h. 5. We concluded that
      there is increased iNOS gene and protein expression associated with increased NF
      kappaB DNA-binding in lungs of sensitized and challenged rats. The increase in
      iNOS expression may underlie the increase in exhaled NO found after allergen
      challenge and may contribute to the development of allergen-induced airway
      hyperresponsiveness.

PMID- 9257900
TI  - Effects of dopamine on L-type Ca2+ current in single atrial and ventricular
      myocytes of the rat.
AB  - 1. The effects of dopamine on the L-type Ca2+ current (ICa,L) of both atrial and
      ventricular single myocytes and on the force of contraction of atrial trabeculae
      in rat heart were investigated. 2. Dopamine increased atrial ICa,L at
      concentrations higher than 1 microM, but had little or no effect on ICa,L at
      lower concentrations. The increase in ICa,L at high concentrations was reversed
      by propranolol and acetylcholine, but not by phentolamine. Activation and
      inactivation kinetics of ICa,L were not altered by dopamine. 3. In rat
      ventricular myocytes in which the D4 receptor mRNA does not express, dopamine (20
      100 microM) also increased the ICa,L amplitude and propranolol reversed this
      effect. 4. Clozapine, a potent D4 receptor antagonist, blocked the augmenting
      effect of dopamine on ICa,L. However, this effect could be explained by beta
      antagonism, since clozapine also inhibited the isoprenaline effect. 5. In the
      atrial trabeculae, the increase in contraction by dopamine (1 to 30 microM) was
      reversed by 1 microM propranolol, but not by 2 microM phentolamine. Low doses of
      dopamine (0.01 to 0.3 microM) did not affect the contraction in the controls or
      during a modest stimulation of the beta-adrenoceptor with 0.01 microM
      isoprenaline. 6. These results indicate that the positive inotropic action of
      dopamine is mediated through direct stimulation of the beta-adrenoceptor in both
      atrial and ventricular myocytes. Involvement of D4 receptor appears unlikely in
      the regulation of the atrial contraction.

PMID- 9257901
TI  - P2-receptor modulation of noradrenergic neurotransmission in rat kidney.
AB  - 1. ATP has previously been shown to act as a sympathetic cotransmitter in the rat
      kidney. The present study analyses the question of whether postganglionic
      sympathetic nerve endings in the kidney possess P2-receptors which modulate
      noradrenaline release. Rat kidneys were perfused with Krebs-Henseleit solution
      containing the noradrenaline uptake blockers cocaine and corticosterone and the
      alpha2-adrenoceptor antagonist rauwolscine. The renal nerves were electrically
      stimulated, in most experiments by 30 pulses applied at 1 Hz. The outflow of
      endogenous noradrenaline (or, in some experiments, of ATP and lactate
      dehydrogenase) as well as the perfusion pressure were measured simultaneously. 2.
      The P2-receptor agonist adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS, 3-30
      microM) reduced the renal nerve stimulation (RNS)-induced outflow of
      noradrenaline (estimated EC50 =8 microM). The P2-receptor antagonist cibacron
      blue 3GA (30 microM) shifted the concentration-inhibition curve for ATPgammaS to
      the right (apparent pKB value 4.7). 3. Cibacron blue 3GA (3-30 microM) and its
      isomer reactive blue 2 (3-30 microM) significantly increased RNS-induced outflow
      of noradrenaline in the presence of the P1-receptor antagonist 8-(p
      sulphophenyl)theophylline (8-SPT, 100 microM) by about 70% and 90%, respectively.
      The P2-receptor antagonist suramin (30-300 microM) only tended to enhance RNS
      induced outflow of noradrenaline. When the nerves were stimulated by short pulse
      trains consisting of 6 pulses applied at 100 Hz (conditions under which
      autoinhibition is inoperative), reactive blue 2 did not affect the RNS-induced
      outflow of noradrenaline. 4. RNS (120 pulses applied at 4 Hz) induced the outflow
      of ATP but not of the cytoplasmatic enzyme lactate dehydrogenase. 5. ATPgammaS (3
      30 microM) concentration-dependently reduced pressor responses to RNS at 1 Hz.
      Cibacron blue 3GA, reactive blue 2 as well as suramin also reduced pressor
      responses to RNS (maximally by 50 to 70%). 6. This study in rat isolated kidney,
      in which the release of endogenous noradrenaline was measured, demonstrates that
      renal sympathetic nerves possess prejunctional P2-receptors that mediate
      inhibition of transmitter release. These prejunctional P2-receptors are activated
      by endogenous ligands, most likely ATP, released upon nerve activity. Both, P2
      receptor agonists and P2-receptor antagonists reduced pressor responses to RNS
      either by inhibiting transmitter release or by blocking postjunctional
      vasoconstrictor P2-receptors.

PMID- 9257902
TI  - mGluR-evoked augmentation of receptor-mediated cyclic AMP formation in neonatal
      and adult rat striatum.
AB  - 1. The effects of selective agonists at group I, II and III metabotropic
      glutamate receptors (mGluRs) on adenosine A2 receptor-mediated cyclic AMP
      formation were compared in cross-chopped slices of adult and neonatal (8 days
      old) rat striatum, in the presence of 1 u ml(-1) adenosine deaminase. 2. The
      group II selective agonist, (2S,1R,2R,3R)-2-(2,3-dicarboxycyclopropyl)glycine
      (DCG-IV), elicited a potentiation of 5'-N-ethylcarboxamidoadenosine (NECA)
      stimulated cyclic AMP production with similar potencies in adult (EC50 value 122
      +/- 35 nM) and neonatal (EC50 value 285 +/-6 nM) brain. In contrast, the group I
      selective agonist (S)-dihydroxyphenylglycine ((S)-DHPG) augmented the NECA cyclic
      AMP response in neonatal striatum (EC50 value 9 +/- 1 microM), but at a
      concentration of 100 microM, (S)-DHPG failed to affect the NECA response in adult
      striatal slices. 3. The potentiation evoked by (S)-DHPG was specific for group I
      mGluRs as (2S,3S,4S,)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG), a group II
      antagonist, was ineffective on the (S)-DHPG (100 microM) response at a
      concentration (500 microM) which reversed a similar augmentation elicited by DCG
      IV (300 nM). Furthermore, a protein kinase C inhibitor (Ro 31-8220, 10 microM)
      markedly reversed the effect of (S)-DHPG without affecting the response to DCG
      IV. 4. The mGluR agonist (2S,3S,4S,)-alpha-(carboxycyclopropyl)glycine (L-CCG-I),
      elicited a greater potentiation of NECA-stimulated cyclic AMP production in
      neonatal striatum in comparison with that observed in adult rat brain. Moreover,
      EC50 values obtained from adult and neonatal striatum were 2 +/-1 microM and 9 +/
      1 microM, respectively. These differences in potency might reflect co-activation
      of both group I and group II mGluRs by L-CCG-I in neonatal striatum. 5. Distinct
      patterns of mGluR expression in various brain areas might account for previous
      conflicting data on the nature of the mGluR able to evoke such potentiated
      responses.

PMID- 9257903
TI  - Electrically-evoked dopamine and acetylcholine release from rat striatal slices
      perfused without magnesium: regulation by glutamate acting on NMDA receptors.
AB  - 1. Rat striatal slices, preincubated with [3H]-dopamine and [14C]-choline, were
      continuously superfused and electrically stimulated. Electrically evoked release
      of [3H]-dopamine and [14C]-acetylcholine (ACh) was not significantly changed by
      elimination of Mg2+ from superfusion buffer, but the basal release of [3H]
      dopamine was doubled. 2. Kynurenic acid (100-800 microM) caused, in the absence
      but not presence of Mg2+, a concentration-dependent decrease in the evoked
      release of these two transmitters. The addition of glycine reversed the
      inhibition of the evoked release of both transmitters caused by kynurenic acid
      (400 microM) in a concentration-dependent manner. In addition, glycine increased
      the evoked release of [3H]-dopamine via a site inhibitable by strychnine (1
      microM). 3. Another two antagonists at N-methyl-D-aspartate (NMDA) receptors, 2
      amino-5-phosphonovaleric acid and dizocilpine, also decreased significantly the
      evoked release of the two transmitters in a concentration-dependent manner in the
      absence, but not presence of Mg2+. By contrast, an antagonist of non-NMDA
      receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) significantly
      decreased the evoked release of the two transmitters in the presence, but not in
      the absence of Mg2+. 4. Electrical field stimulation evoked release of endogenous
      adenosine, and this release tended to be higher in the absence of Mg2+. However,
      the addition of a selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine (200 nM) did not influence the evoked release of the two
      transmitters, showing that the released adenosine is of little importance in
      controlling ACh and dopamine release from striatal slices. Non-NMDA receptors may
      play a similar role when Mg2+ ions are present. 5. The results indicate that NMDA
      receptors activated in the absence of Mg2+ participate in the electrically-evoked
      release of [3H]-dopamine and [14C]-ACh from the striatum.

PMID- 9257904
TI  - Pharmacological characterization of the receptors involved in the beta
      adrenoceptor-mediated stimulation of the L-type Ca2+ current in frog ventricular
      myocytes.
AB  - 1. The whole-cell patch-clamp was used for studying the effects of various beta1-
      and beta2-adrenoceptor agonists and antagonists on the L-type Ca current (Ica) in
      frog ventricular myocytes. 2. Dose-response curves for the effects of
      isoprenaline (non selective beta-agonist), salbutamol (beta2-agonist), dobutamine
      (beta1-agonist) on ICa were obtained in the absence and presence of various
      concentrations of ICI 118551 (beta2-antagonist), metoprolol (beta1-antagonist)
      and xamoterol (partial beta1-agonist) to derive EC50 (i.e. the concentration of
      beta-agonist at which the response was 50% of the maximum) and Emax (the maximal
      response) values by use of a Michaelis equation. Schild regression analysis was
      performed to examine whether the antagonists were competitive and to determine
      the equilibrium dissociation constant (K(B)) for the antagonist-receptor complex.
      3. Isoprenaline increased ICa with an EC50 of 20.0 nM and an Emax of 597%. ICI
      118551 and metoprolol competitively antagonized the effect of isoprenaline with a
      K(B) of 3.80 nM and 207 nM, respectively. 4. Salbutamol increased ICa with an
      EC50 of 290 nM and an Emax of 512%. ICI 118551 and metoprolol competitively
      antagonized the effect of salbutamol with a K(B) of 1.77 nM and 456 nM,
      respectively. 5. Dobutamine increased ICa with an EC50 of 2.40 microM and an Emax
      of 265%. ICI 118551 and metoprolol competitively antagonized the effect of
      dobutamine with a K(B) of 2.84 nM and 609 nM, respectively. 6. Xamoterol had no
      stimulating effect on ICa. However, xamoterol competitively antagonized the
      stimulating effects of isoprenaline, salbutamol and dobutamine on ICa with a K(B)
      of 58-64 nM. 7. We conclude that a single population of receptors is involved in
      the beta-adrenoceptor-mediated regulation of ICa in frog ventricular myocytes.
      The pharmacological pattern of the response of ICa to the different beta
      adrenoceptor agonists and antagonists tested suggests that these receptors are of
      the beta2-subtype.

PMID- 9257905
TI  - Increased function of inhibitory neuronal M2 muscarinic receptors in diabetic rat
      lungs.
AB  - 1. The function of inhibitory neuronal M2 muscarinic receptors in diabetic rat
      lungs was investigated. 2. Neuronal M2 muscarinic receptors inhibit acetylcholine
      release from parasympathetic nerves. Thus, stimulation of neuronal M2 muscarinic
      receptors with muscarinic agonists, such as pilocarpine, inhibits acetylcholine
      release and vagally induced bronchoconstriction. In contrast, blockade of
      neuronal M2 muscarinic receptors with selective M2 muscarinic antagonists, such
      as AF-DX 116, potentiates acetylcholine release and vagally induced
      bronchoconstriction. 3. Rats were made diabetic by streptozotocin (65 mg kg (-1),
      i.v.). After 7 14 days the rats were anaesthetized with urethane (1.5 g kg (-1),
      i.p.), tracheostomized, vagotomized, ventilated and paralysed with suxamethonium
      (30 mg kg (-1), i.v.). Some 7 day diabetic rats were treated with low doses of
      long acting (NPH) insulin (2 units day (-1), s.c.) for 7 days before
      experimentation. This dose of insulin was not sufficient to restore
      normoglycaemia in diabetic rats. Thus, insulin-treated diabetic rats remained
      hyperglycaemic. 4. Distal electrical stimulation (5 70 Hz, 6 s, 40 V, 0.4 ms) of
      the vagi caused bronchoconstriction, measured as an increase in inflation
      pressure and bradycardia. In diabetic rats, vagally induced bronchoconstriction
      was significantly depressed vs controls. In contrast, bronchoconstriction caused
      by i.v. acetylcholine was similar in diabetic and control animals. 5. The
      function of neuronal M2 muscarinic receptors was tested with the muscarinic
      agonist pilocarpine (0.001-100.0 microg kg (-1), i.v.) and the antagonist AF-DX
      116 (0.01-3.0 mg kg (-1), i.v.). Pilocarpine inhibited vagally-induced
      bronchoconstriction (30 Hz, 20-40 V, 0.4 ms at 6 s) and AF-DX 116 potentiated
      vagally-induced bronchoconstriction (20 Hz, 20-40 V, 0.4 ms at 6 s) to a
      significantly greater degree in diabetic rats compared to controls. 6. Both
      frequency-dependent vagally-induced bronchoconstriction and M2 muscarinic
      receptor function could be restored to nearly control values in diabetic rats
      treated with low doses of insulin. 7. Displacement of [3H]QNB (1 nM) with the
      agonist carbachol (10.0 nM-10.0 mM) from diabetic cardiac M2 muscarinic receptors
      revealed a half log increase in agonist binding affinity at both the high and low
      affinity binding sites vs controls. In contrast, M2 receptors from insulin
      treated diabetic rat hearts showed no significant difference in binding affinity
      vs controls. 8. These data show that neuronal M2 muscarinic receptors in the
      lungs have increased function in diabetic rats, suggesting that insulin modulates
      M2 muscarinic receptor function.

PMID- 9257906
TI  - Differential effects of zidovudine and zidovudine triphosphate on mitochondrial
      permeability transition and oxidative phosphorylation.
AB  - 1. The effects of zidovudine (ZDV) and zidovudine triphosphate (ZDV-3P) on Ca2+
      induced mitochondrial permeability transition (MPT), respiratory control ratio
      (RCR) and ATP synthesis have been investigated on isolated rat liver
      mitochondria. 2. ZDV slightly but significantly decreased RCR and ATP synthesis
      but was ineffective in inhibiting MPT. In contrast, ZDV-3P did not alter RCR and
      ATP synthesis but strongly inhibited MPT (IC50 = 3.0 +/- 0.9 microM). 3. The
      effect of ZDV-3P on mitochondrial swelling required a preincubation time. When
      incubated 10 min with mitochondria, ZDV-3P (8 microM) totally inhibited the rate
      of swelling. 4. ADP, ATP and atractyloside, which are agents known to interact
      with the mitochondrial adenine nucleotide carrier (ANC), antagonized the effect
      of ZDV-3P on mitochondrial swelling. Indeed, the IC50 value of ZDV-3P increased
      from 3.0 to 17.4, 93.6 and 66.5 microM, in the presence of 20 microM, ADP, ATP or
      atractyloside, respectively. 5. ZDV-3P did not displace [3H]-ATP from its
      mitochondrial binding site(s) whereas ADP and atractyloside did, suggesting that
      ZDV-3P and [3H]-ATP do not share the same binding sites. 6. ZDV-3P did not affect
      either mitochondrial respiration or ATP synthesis but inhibited Ca2+-dependent
      mitochondrial swelling. It was concluded that mitochondrial toxic effects
      observed during the chronic administration of ZDV cannot be related to its active
      metabolite (ZDV-3P).

PMID- 9257907
TI  - Cellular mechanisms underlying carbachol-induced oscillations of calcium
      dependent membrane current in smooth muscle cells from mouse anococcygeus.
AB  - 1. At a holding potential of -40 mV, carbachol (50 microM) produced a complex
      pattern of inward currents in single smooth muscle cells freshly isolated from
      the mouse anococcygeus. Membrane currents were monitored by the whole-cell
      configuration of the patch-clamp technique. Previous work has identified the
      first, transient component as a calcium-activated chloride current (ICl(Ca)) and
      the second sustained component as a store depletion-operated non-selective cation
      current (I(DOC)). The object of the present study was to examine the cellular
      mechanisms underlying the third component, a series of inward current
      oscillations (I(oscil)) superimposed on I(DOC). 2. Carbachol-induced I(oscil)
      (amplitude 97 +/- 11 pA; frequency 0.26 +/- 0.02 Hz) was inhibited by the
      chloride channel blocker anthracene-9-carboxylic acid (A-9-C; 1 mM), and by
      inclusion of 1 mM EGTA in the patch-pipette filling solution. 3. In calcium-free
      extracellular medium (plus 1 mM EGTA), carbachol produced an initial burst of
      oscillatory current which lasted 94 s before decaying to zero; I(oscil) could be
      restored by re-admission of calcium. The frequency, but not the amplitude, of
      I(oscil) increased with increasing concentrations of extracellular calcium (0.5
      10 mM). 4. Inclusion of the inositol triphosphate (IP3) receptor antagonist
      heparin (5 mg ml(-1) in the patch-pipette filling solution, or pretreatment of
      cells with the sarcoplasmic reticulum (SR) calcium ATPase inhibitor cyclopiazonic
      acid (CPA; 10 microM), prevented the activation of I(oscil) by carbachol.
      Caffeine (10 mM) activated both ICl(Ca) and I(DOC) and prevented the induction of
      I(oscil) by carbachol. Caffeine and CPA also abolished I(oscil) in the presence
      of carbachol, as did both a low (3 microM) and a high (30 microM) concentration
      of ryanodine. 5. Carbachol-induced I(oscil) was abolished by the general calcium
      entry blocker SKF 96365 (10 MM) and by Cd2+ (100 microM), but was unaffected by
      La3+ (400 microM). As found previously, I(DOC) was also blocked by SKF 96365 and
      Cd2+, but not La3+; the inhibition of I(DOC) preceded the abolition of I(oscil)
      by 27 s with SKF 96365 and by 30 s with Cd2+. Nifedipine (1 microM) produced a
      partial inhibition of the carbachol-induced I(oscil) frequency at holding
      potentials of -20 mV and -60 mV and, in addition, reduced I(DOC) at -60 mV by
      18%. 6. It is concluded that carbachol-induced inward current oscillations in
      mouse anococcygeus cells are due to a calcium-activated chloride current, and
      reflect oscillatory changes in cytoplasmic calcium ion concentration. These
      calcium oscillations are derived primarily from the SR stores, but entry of
      calcium into the cell is necessary for store replenishment and maintenance of the
      oscillations. Capacitative calcium entry (via I(DOC) appears to be important not
      only for sustained contraction of this tissue, but also as a route for re-filling
      of the SR and, therefore, represents an important target for the development of
      novel and selective drugs.

PMID- 9257908
TI  - Stellettamide-A, a novel inhibitor of calmodulin, isolated from a marine sponge.
AB  - 1. Stellettamide A (ST-A), a novel marine toxin isolated from a marine sponge,
      inhibited high K+(72.7 mM)-induced contraction in the smooth muscle of guinea-pig
      taenia coli with an IC50 of 88 microM. 2. In the taenia permeabilized with Triton
      X-100, ST-A inhibited Ca2+ (3 and 10 microM)-induced contractions with an IC50 of
      46 microM for 3 microM Ca2+ and 105 microM for 10 microM Ca2+. In the
      permeabilized taenia, calyculin-A (300 nM), a potent inhibitor of type-1 and type
      2A phosphatases, induced sustained contraction in the absence of Ca2+. ST-A had
      no effect on this contraction. 3. ST-A inhibited Mg2+-ATPase activity in native
      actomyosin prepared from chicken gizzard with an IC50 of 25 microM. 4. In a
      reconstituted smooth muscle contractile system containing calmodulin, myosin
      light chain (MLC) and MLC kinase, ST-A inhibited MLC phosphorylation with an IC50
      of 152 microM. The inhibitory effect of ST-A was antagonized by increasing the
      concentration of calmodulin. 5. ST-A inhibited calmodulin activity, assessed by
      Ca2+/calmodulin-dependent enzymes, (Ca2+-Mg2+)-ATPase of erythrocyte membrane,
      with an IC50 of 100 microM and phosphodiesterase prepared from bovine cardiac
      muscle with an IC50 of 52 microM. The inhibitory effect on phosphodiesterase
      activity was antagonized by increasing the calmodulin concentration. 6.
      Interaction between ST-A and calmodulin was demonstrated by instantaneous
      quenching of the intrinsic tyrosine fluorescence of calmodulin by ST-A (3-300
      microM). Similar results were obtained in the presence or absence of Ca2+
      suggesting that ST-A binds to calmodulin and that Ca2+ is not essential for the
      binding of ST-A to calmodulin. 7. These results suggest that ST-A, isolated from
      marine metabolites, is a novel inhibitor of calmodulin.

PMID- 9257909
TI  - Role of endothelium in regulation of smooth muscle membrane potential and tone in
      the rabbit middle cerebral artery.
AB  - 1. The characteristic features of the endothelium-mediated regulation of the
      electrical and mechanical activity of the smooth muscle cells of cerebral
      arteries were studied by measuring membrane potential and isometric force in
      endothelium-intact and -denuded strips taken from the rabbit middle cerebral
      artery (MCA). 2. In endothelium-intact strips, histamine (His, 3-10 microM) and
      high K+ (20-80 mM) concentration-dependently produced a transient contraction
      followed by a sustained contraction. Noradrenaline (10 microM), 5
      hydroxytryptamine (10 microM) and 9,11-epithio-11, 12-methano-thromboxane A2 (10
      nM) each produced only a small contraction (less than 5% of the maximum K+
      induced contraction). 3. N(G)-nitro-L-arginine (L-NOARG, 100 microM), but not
      indomethacin (10 microM), greatly enhanced the phasic and the tonic contractions
      induced by His (1-10 microM) in endothelium-intact, but not in endothelium
      denuded strips, suggesting that spontaneous or basal release of nitric oxide (NO)
      from endothelial cells potently attenuates the His-induced contractions.
      Acetylcholine (ACh, 0.3-3 microM) caused concentration-dependent relaxation
      (maximum relaxation by 89.7 +/- 7.5%, n=4, P<0.05) when applied to endothelium
      intact strips precontracted with His. L-NOARG had little effect on this ACh
      induced relaxation (n=4; P<0.05). Apamin (0.1 microM), but not glibenclamide (3
      microM), abolished the relaxation induced by ACh (0.3-3 microM) in L-NOARG
      treated strips (n=4, P<0.05). 4. In endothelium-intact tissues, His (3 microM)
      depolarized the smooth muscle membrane potential (by 4.4 +/- 1.8 mV, n = 12, P <
      0.05) whereas ACh (3 microM) caused membrane hyperpolarization (-20.9 +/- 3.0 mV,
      n = 25, P< 0.05). The ACh-induced membrane hypepolarization persisted after
      application of L-NOARG (-23.5 +/- 5.9 mV, n=8, P<0.05) or glibenclamide (-20.6 +/
      5.4 mV, n=5, P<0.05) but was greatly diminished by apamin (reduced to - 5.8 +/-
      3.2 mV, n = 3, P< 0.05). 5. Sodium nitroprusside (0.1-10 microM) did not
      hyperpolarize the smooth muscle cell membrane potential (0.2 +/- 0.3 mV, n=4,
      P>0.05) but it greatly attenuated the His-induced contraction in endothelium
      denuded strips (n-4, P<0.05). 6. These results suggest that, under the present
      experimental conditions: (i) spontaneous or basal release of NO from endothelial
      cells exerts a significant negative effect on agonist-induced contractions in
      rabbit MCA, and (ii) ACh primarily activates the release of endothelium-derived
      hyperpolarizing factor (EDHF) in rabbit MCA.

PMID- 9257910
TI  - Involvement of protein kinase C in reduced relaxant responses to the NO/cyclic
      GMP pathway in piglet pulmonary arteries contracted by the thromboxane A2-mimetic
      U46619.
AB  - 1. Impairment of nitric oxide (NO)/cyclic GMP production and/or increased
      activities of thromboxane A2 (TXA2) and endothelin-1 (ET-1) have been associated
      with pulmonary hypertension. We have analysed the interactions of noradrenaline
      (NA), the TXA2-mimetic U46619 and ET-1 with the relaxation induced via cyclic GMP
      in isolated piglet intrapulmonary arteries. 2. The contractions induced by NA
      were augmented by endothelium removal or by methylene blue and pre-contracted
      rings were fully relaxed by acetylcholine, sodium nitroprusside (SNP), atrial
      natriuretic peptide and 8-bromo-cyclic GMP. In contrast, U46619- and ET-1 induced
      contractions were endothelium-independent and only partially relaxed by the
      latter vasodilators. Whereas the reduced responses to SNP in arteries contracted
      by U46619 were independent of the U46619-induced tone, a higher concentration of
      ET-1 (tone higher than that induced by NA) was required to reduce the vasodilator
      responses to SNP. NA, U46619 and ET-1 had no effect on the SNP-induced increases
      in cyclic GMP. 3. The reduced relaxant responses to SNP in arteries pre
      contracted by U46619 were specific for piglet pulmonary arteries since they were
      not observed in piglet mesenteric or coronary arteries or in rat pulmonary
      arteries. Furthermore, there were no differences in the relaxant response to the
      adenylate cyclase activator forskolin in piglet pulmonary arteries pre-contracted
      by either NA, U46619 or ET-1. 4. SNP-induced relaxation was inhibited by
      thapsigargin (but not by inhibition of the membrane Na+/ K+ ATPase nor K+
      channels) indicating a role for Ca2+ sequestration by the Ca2+ ATPase in the
      effects of SNP. 5. The phorbol ester 12-myristate, 13-acetate inhibited the
      relaxant response to SNP. The inhibitory effect of U46619 on SNP-induced
      relaxation was abolished by the protein kinase C inhibitor (PKC) staurosporine
      suggesting that PKC may be a part of the signal transduction mechanism. 6. In
      summary, piglet pulmonary arteries when activated by a TXA2-mimetic show
      abnormally reduced relaxant responses to the NO/cyclicGMP pathway. This effect
      appears to be mediated by activation of PKC.

PMID- 9257911
TI  - Effect of SB-205384 on the decay of GABA-activated chloride currents in granule
      cells cultured from rat cerebellum.
AB  - 1. 4-Amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyrid ine-3
      carboxylic acid, but-2-ynyl ester (SB-205384) and other gamma-aminobutyric
      acid(A) (GABA(A)) receptor modulators were tested for their effects on GABA
      activated chloride currents in rat cerebellar granule cells by use of the whole
      cell patch clamp technique. 2. The major effect of SB-205384 on GABA(A)-activated
      current was an increase in the half-life of decay of the response once the
      agonist had been removed. This is in contrast to many GABA(A) receptor modulators
      that have previously been shown to potentiate GABA-activated currents. 3. This
      profile could be explained if SB-205384 stabilizes the channel in open and
      desensitized states so that channel closing is dramatically slowed. Such a
      modulatory profile may produce a novel behavioural profile in vivo.

PMID- 9257912
TI  - The spasmogenic effects of vanadate in human isolated bronchus.
AB  - 1. Inhalation of vanadium compounds, particularly vanadate, is a cause of
      occupational bronchial asthma. We have now studied the action of vanadate on
      human isolated bronchus. Vanadate (0.1 microM-3 mM) produced concentration
      dependent, well-sustained contraction. Its -logEC50 was 3.74 +/- 0.05 (mean +/-
      s.e.mean) and its maximal effect was equivalent to 97.5 +/- 4.2% of the response
      to acetylcholine (ACh, 1 mM). 2. Vanadate (200 microM)-induced contraction of
      human bronchus was epithelium-independent and was not inhibited by indomethacin
      (2.8 microM), zileuton (10 microM), a mixture of atropine, mepyramine and
      phentolamine (each at 1 microM), or by mast cell degranulation with compound
      48/80. 3. Vanadate (200 microM)-induced contraction was unaltered by tissue
      exposure to verapamil or nifedipine (each 1 microM) or to a Ca2+-free, EGTA (0.1
      mM)-containing physiological salt solution (PSS). However, tissue incubation with
      ryanodine (10 microM) in Ca2+-free, EGTA (0.1 mM)-containing PSS reduced vanadate
      induced contraction. A series of vanadate challenges was made in tissues exposed
      to Ca2+-free EGTA (0.1 mM)-containing PSS with the object of depleting
      intracellular Ca2+ stores. In such tissues cyclopiazonic acid (CPA; 10 microM)
      prevented Ca2+-induced recovery of vanadate-induced contraction. 4. Tissue
      incubation in K+-rich (80 mM) PSS, K+-free PSS, or PSS containing ouabain (10
      microM) did not alter vanadate (200 microM)-induced contraction. Ouabain (10
      microM) abolished the K+-induced relaxation of human bronchus bathed in K+-free
      PSS. This action was not shared by vanadate (200 microM). The tissue content of
      Na+ was increased and the tissue content of K+ was decreased by ouabain (10
      microM). In contrast, vanadate (200 microM) did not alter the tissue content of
      these ions. Tissue incubation in a Na+-deficient (25 mM) PSS or in PSS containing
      amiloride (0.1 mM) markedly inhibited the spasmogenic effect of vanadate (200
      microM). 5. Vanadate (200 microM)-induced contractions were markedly reduced by
      tissue treatment with each of the protein kinase C (PKC) inhibitors H-7 (10
      microM), staurosporine (1 microM) and calphostin C (1 microM). Genistein (100
      microM), an inhibitor of protein tyrosine kinase, also reduced the response to
      vanadate. 6 Vanadate (0.1-3 mM) and ACh (1 microM- 3 mM) each increased inositol
      phosphate accumulation in bronchus. Such responses were unaffected by a Ca2+-free
      medium either alone or in combination with ryanodine (10 microM). 7. In human
      cultured tracheal smooth muscle cells, histamine (100 microM) and vanadate (200
      microM) each produced a transient increase in intracellular Ca2+ concentration
      ([Ca2+]i). 8. Intracellular microelectrode recording showed that the contractile
      effect of vanadate (200 microM) in human bronchus was associated with cellular
      depolarization. 9. It is concluded that vanadate acts directly on human bronchial
      smooth muscle, promoting the release of Ca2+ from an intracellular store. The
      Ca2+ release mechanism involves both the production of inositol phosphate second
      messengers and inhibition of Ca-ATPase. The activation of PKC plays an important
      role in mediating vanadate-induced contraction at values of [Ca2+]i that are
      close to basal.

PMID- 9257913
TI  - Effects of moexiprilat on oestrogen-stimulated cardiac fibroblast growth.
AB  - 1. The effects of 2-2-(1-(ethoxycarbonyl)-3-phenylpropyl)-[amino-oxopropyl]-6,7
      dimethoxy- 1,2,3,4-tetrahydroisoquinoline-3 carboxylic acid (moexiprilat), 17beta
      oestradiol (E2), oestrone (ES) and angiotensin II (AII) on growth and activation
      of oestrogen receptors and the immediate-early gene egr-1 were investigated in
      neonatal rat cardiac fibroblasts of female and male origin. 2. In BrdU
      proliferation assays, oestrone (10(-7)- 10(-9) M) stimulated cardiac fibroblast
      growth in a concentration-dependent fashion (maximum at 10(-7) M, 4.0 fold +/-
      0.14 in female and 3.1 fold +/- 0.06 in male cells, n=9, P<0.05), while E2 (10(
      7)-10(-9) M) had no effect. Moexiprilat (10(-7)M) completely inhibited oestrone
      induced cardiac fibroblast growth. 3. Angiotensin II (10(-7) M) induced cardiac
      fibroblast growth (female 4.1 fold +/- 0.1/male 3.9 fold +/- 0.2; n=9, P<0.05).
      Angiotensin II induced oestrogen receptor (maximum 21.8 fold at 60 min) and egr-1
      (maximum 47.5 fold at 60 min) expression in a time-dependent fashion. 4. In
      immunoblot experiments, oestrogen activated oestrogen receptor (ES: 12.8 fold +/-
      2.0; E2: 14.7 fold +/- 4.9; n=3, P<0.05) and egr-1 (ES: 5.1 fold, +/- 0.24; E2:
      3.8 fold, +/- 0.25; n=3, P<0.05) expression. The induction of oestrogen receptor
      and egr-1 protein expression was time-dependent and inhibited by moexiprilat. 5.
      Our results show that oestrone and 17beta-oestradiol reveal a significant
      difference in their potential to activate cardiac fibroblast growth in female and
      male cells and that oestrone-stimulated growth is inhibited by moexiprilat. The
      inhibition of oestrone-stimulated cardiac fibroblast growth by moexiprilat may
      contribute to the beneficial effects seen in postmenopausal women with
      hypertensive heart disease treated with ACE inhibitors.

PMID- 9257914
TI  - Predominant role of A1 adenosine receptors in mediating adenosine induced
      vasodilatation of rat diaphragmatic arterioles: involvement of nitric oxide and
      the ATP-dependent K+ channels.
AB  - 1. We investigated, by intravital microscopy in rats, the role of the subtypes of
      adenosine receptors A1 (A1/AR) and A2 (A2AR) in mediating adenosine-induced
      vasodilatation of second and third order arterioles of the diaphragm. 2.
      Adenosine, and the A1AR selective agonists R(-)-N6-(2-phenylisopropyl)-adenosine
      (R-PIA) and N6-cyclo-pentyl-adenosine (CPA) induced a similar concentration
      dependent dilatation of diaphragmatic arterioles. The non selective A2AR subtype
      agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl) ethyl]adenosine (DPMA)
      also dilated diaphragmatic arterioles but induced a significantly smaller
      dilatation than adenosine. By contrast the selective A(2a)AR subtype agonist 2-[p
      (2-carboxyethyl)phenyl amino]-5'-N-ethyl carboxamido adenosine (CGS 21680) did
      not modify diaphragmatic arteriolar diameter. 3. The non selective adenosine
      receptor antagonist 1,3-dipropyl-8-p-sulphophenylxanthine (SPX, 100 microM) and
      the selective A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX, 50 nM)
      significantly attenuated adenosine-induced dilatation of diaphragmatic
      arterioles. By contrast, adenosine significantly dilated diaphragmatic arterioles
      in the presence of A2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 10
      microM). 4. The dilatation induced by adenosine was unchanged by the mast cell
      stabilizing agent sodium cromoglycate (cromolyn, 10 microM). 5. The nitric oxide
      (NO) synthase inhibitor N omega-nitro-L-arginine (L-NOARG, 300 microM) attenuated
      the dilatation induced by adenosine, and by the A1AR and A2AR agonists. 6. The
      ATP-dependent K+ channel blocker glibenclamide (3 microM) significantly
      attenuated diaphragmatic arteriolar dilatation induced by adenosine and by the
      A1AR agonists R-PIA and CPA. By contrast, glibenclamide did not significantly
      modify arteriolar dilatation induced by the A2AR agonist DPMA. 7. These findings
      suggest that adenosine-induced dilatation of diaphragmatic arterioles in the rat
      is predominantly mediated by the A1AR, via the release of NO and activation of
      the ATP-dependent K+ channels.

PMID- 9257915
TI  - Dissociation of the effects of the antitumour ether lipid ET-18-OCH3 on cytosolic
      calcium and on apoptosis.
AB  - 1. We have compared the effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3
      phosphocholine (ET-18-OCH3) on the cytosolic free calcium concentration ([Ca2+]i)
      and on apoptosis in several normal and leukaemia cells, including human
      polymorphonuclear neutrophils (PMNs), U937 cells, and undifferentiated as well as
      dimethylsulphoxide-differentiated HL60 cells (uHL60 and dHL60, respectively). 2.
      ET-18-OCH3 produced apoptosis, as evidenced by DNA degradation into
      oligonucleosome-size fragments, in U937 and uHL60 cells, but not in dHL60 cells
      or PMNs. 3. ET-18-OCH3 induced an increase in [Ca2+]i mediated through the
      platelet-activating factor (PAF) receptor in U937, dHL60 cells and PMNs, as shown
      by cross-desensitization experiments and by prevention of the [Ca2+]i changes by
      the PAF antagonist WEB-2170. The EC50 values for the increase in [Ca2+]i induced
      by PAF and ET-18-OCH3 were 5 x 10(-11) and 2.5 x 10(-7) M, respectively. In uHL60
      cells the effect of ET-18-OCH3 on [Ca2+]i was very small and was not affected by
      WEB-2170. 4. PAF did not produce apoptosis in any of the cell types tested. WEB
      2170 did not prevent the apoptosis induced by ET-18-OCH3. 5. The uptake of [3H]
      ET-18-OCH3 was much larger in U937 and uHL60 cells than in dHL60 cells and PMNs.
      6. Our results indicate that the apoptotic effect of ET-18-OCH3 is not related to
      the changes in [Ca2+]i, effected by interaction with plasma membrane PAF
      receptors, but to other actions which are associated with the uptake of this drug
      into the cells.

PMID- 9257916
TI  - A comparative study of the effects of three guanylyl cyclase inhibitors on the L
      type Ca2+ and muscarinic K+ currents in frog cardiac myocytes.
AB  - 1. To investigate the participation of guanylyl cyclase in the muscarinic
      regulation of the cardiac L-type calcium current (ICa), we examined the effects
      of three guanylyl cyclase inhibitors, 1H-[1,2,4]oxidiazo-lo[4,3-a]quinoxaline-1
      one (ODQ), 6-anilino-5,8-quinolinedione (LY 83583), and methylene blue (MBlue),
      on the beta-adrenoceptor; muscarinic receptor and nitric oxide (NO) regulation of
      ICa and on the muscarinic activated potassium current I(K,ACh), in frog atrial
      and ventricular myocytes. 2. ODQ (10 microM) and LY 83583 (30 microM) antagonized
      the inhibitory effect of an NO-donor (S-nitroso-N-acetylpenicillamine, SNAP, 1
      microM) on the isoprenaline (Iso)-stimulated ICa which was consistent with their
      inhibitory action on guanylyl cyclase. However, MBlue (30 microM) had no effect
      under similar conditions. 3. In the absence of SNAP, LY 83583 (30 microM)
      potentiated the stimulations of ICa by either Iso (20 nM), forskolin (0.2 microM)
      or intracellular cyclic AMP (5-10 microM). ODQ (10 microM) had no effect under
      these conditions, while MBlue (30 microM) inhibited the Iso-stimulated ICa. 4. LY
      83583 and MBlue, but not ODQ, reduced the inhibitory effect of up to 10 microM
      acetylcholine (ACh) on ICa. 5. MBlue, but not LY 83583 and ODQ, antagonized the
      activation of I(K,ACh) by ACh in the presence of intracellular GTP, and this
      inhibition was weakened when I(K,ACh) was activated by intracellular GTPgammaS.
      6. The potentiating effect of LY 83583 on Iso-stimulated ICa was absent in the
      presence of either DL-dithiothreitol (DTT, 100 microM) or a combination of
      superoxide dismutase (150 u ml(-1)) and catalase (100 u ml(-1)). 7. All together,
      our data demonstrate that, among the three compounds tested, only ODQ acts in a
      manner which is consistent with its inhibitory action on the NO-sensitive
      guanylyl cyclase. The two other compounds produced severe side effects which may
      involve superoxide anion generation in the case of LY 83583 and alteration of
      beta-adrenoceptor and muscarinic receptor-coupling mechanisms in the case of M
      Blue.

PMID- 9257917
TI  - Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle.
AB  - 1. Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM).
      Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ
      in their analgesic and anaesthetic effects. The aim of this study was to
      determine whether there was a difference between the enantiomers in their ability
      to relax isolated ASM and to explore mechanisms responsible for any observed
      differences. 2. Canine tracheal smooth muscle strips were loaded with fura-2 and
      mounted in a photometric system to measure simultaneously force and [Ca2+]i.
      Calcium influx was estimated by use of a manganese quenching technique. 3. In
      strips stimulated with 0.1 microM ACh (EC50) R(-)-ketamine (1-100 microM) caused
      a significantly greater concentration-dependent decrease in force (P<0.0001) and
      [Ca2+]i than S(+)-ketamine (1-100 microM) (P<0.0005). In contrast, there was no
      significant difference between the enantiomers in their ability to inhibit
      calcium influx (45% decrease in influx rate for R(-)-ketamine and 44% for S(+)
      ketamine, P =0.782). In strips contracted with 24 mM isotonic KCI (which
      activates voltage-operated calcium channels), the enantiomers modestly decreased
      force and [Ca2+]i; there was no significant difference between the enantiomers in
      their effects on force (P=0.425) or [Ca2+]i (P=0.604). 4. The R(-)-enantiomer of
      ketamine is a more potent relaxant of ACh-induced ASM contraction than the S(+)
      enantiomer. This difference appears to be caused by differential actions on
      receptor-operated calcium channels.

PMID- 9257918
TI  - Alterations in endothelium-dependent hyperpolarization and relaxation in
      mesenteric arteries from streptozotocin-induced diabetic rats.
AB  - 1. The aim of this study was to determine whether endothelium-dependent
      hyperpolarization and relaxation are altered during experimental diabetes
      mellitus. Membrane potentials were recorded in mesenteric arteries from rats with
      streptozotocin-induced diabetes and age-matched controls. The resting membrane
      potentials were not significantly different between control and diabetic
      mesenteric arteries (-55.3 +/- 0.5 vs -55.6 +/- 0.4 mV). However, endothelium
      dependent hyperpolarization produced by acetylcholine (ACh; 10(-8)-10(-5) M) was
      significantly diminished in amplitude in diabetic arteries compared with that in
      controls (maximum -10.4 +/- 1.1 vs -17.2 +/- 0.8mV). Furthermore, the
      hyperpolarizing responses of diabetic arteries were more transient. 2. ACh
      induced hyperpolarization observed in control and diabetic arteries remained
      unaltered even after treatment with 3 x 10(-4) M N(G)-nitro-L-arginine (L-NOARG),
      10(-5) M indomethacin or 60 u ml (-1) superoxide dismutase. 3. Endothelium
      dependent hyperpolarization with 10(-6) M A23187, a calcium ionophore, was also
      decreased in diabetic arteries compared to controls (-8.3 +/- 1.4 vs -18.0 +/-
      1.9 mV). However, endothelium-independent hyperpolarizing responses to 10(-6) M
      pinacidil, a potassium channel opener, were similar in control and diabetic
      arteries (-20.0 +/- 1.4 vs - 19.2 +/- 1.1 mV). 4. The altered endothelium
      dependent hyperpolarizations in diabetic arteries were almost completely
      prevented by insulin therapy. Endothelium-dependent relaxations by ACh in the
      presence of l0(-4) M L-NOARG and 10(-5) M indomethacin in diabetic arteries were
      also reduced and more transient compared to controls. 5. These data indicate that
      endothelium-dependent hyperpolarization is reduced by diabetes, and this would,
      in part, account for the impaired endothelium-dependent relaxations in mesenteric
      arteries from diabetic rats.

PMID- 9257919
TI  - Interactions between loreclezole, chlormethiazole and pentobarbitone at GABA(A)
      receptors: functional and binding studies.
AB  - 1. Interactions were investigated between loreclezole, chlormethiazole and
      pentobarbitone as potentiators of depolarization responses mediated by gamma
      aminobutyric acid(A) (GABA(A)) receptors on afferent nerve terminals in the rat
      cuneate nucleus in vitro. These drugs were also compared as modulators of [3H]
      flunitrazepam (FNZ) binding to synaptic membranes prepared from rat whole brain
      homogenate. 2. In rat cuneate nucleus slices, the drugs shifted muscimol log dose
      response lines to the left in an approximately parallel fashion with the result
      that 200 microM chlormethiazole potentiated muscimol responses by 0.567 +/- 0.037
      log unit (mean +/- s.e.mean, n = 4) while loreclezole gave a maximal potentiation
      at 10 microM of only 0.121 +/- 0.037 (n=6) log unit and 0.071 +/- 0.039 (n=22) at
      50 microM. 3. While 50 microM chlormethiazole and 30 microM pentobarbitone showed
      no significant interactions between each other when potentiating muscimol
      responses in combination, 50 microM loreclezole in combination with either
      chlormethiazole or pentobarbitone attenuated their potentiating effects, possibly
      by inducing desensitization of GABA(A) receptors. 4. In the [3H]-FNZ binding
      studies on well-washed membranes, loreclezole enhanced binding to a maximum of
      47.3 +/- 2.83% of control (mean +/- s.e.mean, n = 3) at 300 microM. Scatchard
      analysis revealed no change in Bmax but a decrease in K(D) for [3H]-FNZ from 3.9
      +/- 0.29 nM to 2.7 +/- 0.10 nM (mean +/- s.e.mean, n=4) in the presence of 100
      microM loreclezole. In contrast, 100 microM chlormethiazole caused no
      potentiation. A small component of the enhancement by loreclezole could be
      blocked by 100 microM bicuculline and could also be blocked by 100 microM
      chlormethiazole. It seems likely that the effects on [3H]-FNZ binding are due
      predominantly to direct actions of the drugs on the GABA(A) receptor and are
      separate from the GABA-potentiating effects. 5. The results indicate distinctly
      different profiles of action for loreclezole, chlormethiazole and pentobarbitone
      on GABA(A) receptors.

PMID- 9257920
TI  - Spatial heterogeneity of the effects of calcitonin gene-related peptide (CGRP) on
      the microvasculature of ligaments in the rabbit knee joint.
AB  - 1. Experiments were performed in anaesthetized rabbits to examine the effects of
      calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP8-37 on blood
      flow to the medial collateral ligament of the knee joint. 2. Topical application
      of CGRP (10(-13) to 10(-9) mol) to the exposed external surface of eight knee
      joints resulted in dose-dependent dilatation of vessels in both the ligament and
      the joint capsule. The magnitude of this response varied significantly in
      different regions of the medial collateral ligament, with the 10(-9) mol dose of
      CGRP giving the maximum response (101.5 +/- 25.3% increase) at the femoral
      insertion site of the medial collateral ligament and lowest (23.1 +/- 8.8%) at
      the tibial insertion site. 3. Topical application of CGRP8-37 (0.1, 1 and 10
      nmol) produced dose-dependent constriction of vessels in the ligament and the
      joint capsule in five knees, with a trend towards the greatest effect occurring
      at the femoral insertion site (45.8 +/- 8.1% reduction in blood flow). With the
      10 nmol dose, the vasoconstrictor response at the femoral insertion site differed
      significantly (P<0.05) from the responses obtained at the tibial insertion and
      joint capsule sites. 4. Topical application of CGRP8-37 (0.1, 1 and 10 nmol) to
      four chronically denervated knees produced substantially smaller vasoconstrictor
      responses at all sites. At the femoral insertion site, where 10 nmol CGRP8-37
      normally produces a 45.8 +/- 8.1% reduction in blood flow (n=8), ten days
      following denervation this response was reduced to 6.5 +/- 6.1%, this difference
      being significant (P=0.01). 5. Adrenaline was applied topically to augment blood
      vessel tone, in order to establish how effectively co-administration of CGRP
      would offset this increase in tone. Adrenaline (10(-10) mol) produced
      vasoconstriction at all sites (n=6). In the capsule this vasoconstriction was
      virtually abolished when CGRP (10(-9) mol) was co-administered with adrenaline
      but in the ligament vasodilatation occurred at all sites. This vasodilatation was
      significantly greater at the femoral insertion site compared to the tibial
      insertion and mid ligament sites (P<0.05 for both) and the capsule (P<0.01). 6.
      Topical application of substance P (10(-10) or 10(-9) mol) failed to elicit
      dilatation of ligament blood vessels. 7. These results suggest that endogenous
      CGRP may play an important role in regulating blood flow to different structures
      in and around the knee joint.

PMID- 9257921
TI  - Effects of the wasp venom peptide, mastoparan, on GTP hydrolysis in rat brain
      membranes.
AB  - 1. The effects of mastoparan, a wasp venom toxin, on GTP hydrolyzing activity
      were examined in rat brain membranes. 2. Mastoparan inhibited the low-affinity
      GTPase activity, defined as the amount of 32Pi released from 0.3 microm [gamma
      32P]-GTP in the presence of 100 microM unlabelled GTP, in a concentration
      dependent manner. This inhibitory effect of mastoparan on low-affinity GTPase
      activity was diminished by increasing concentrations of UDP and was completely
      attenuated at 20 mM, indicating that activation of nucleoside diphosphokinase
      (NDPK) is inolved in the phenomenon. 3. In the presence of 20 mM UDP, mastoparan
      stimulated the high-affinity GTPase activity by increasing the Vmax value without
      affecting the apparent K(M) for GTP. Mastoparan-stimulated high-affinity GTPase
      activity was apparent at concentrations higher than 1 microM, in a concentration
      dependent manner, but without saturation even at 100 microM. 4. Mastoparan
      induced high-affinity GTPase activity showed a characteristic sensitivity to
      MgCl2, quite different from that seen in L-glutamate-stimulated activity, a
      representative of receptor-mediated G-protein activation. 5. There appeared to be
      a simple additive interaction between mastoparan- and L-glutamate-stimulated high
      affinity GTPase activities, indicting that distinct pools of G-proteins are
      involved in receptor-independent and receptor-mediated G-protein activation. 6.
      These results suggest that G-proteins in brain membranes are functionally altered
      by mastoparan through multiple mechanisms of action and that the mastoparan
      induced, direct G-protein activating process lacks a synergistic or antagonistic
      interaction with an agonist-induced, receptor-mediated activation of G-proteins.

PMID- 9257922
TI  - The mechanisms of enhancement and inhibition of field stimulation responses of
      guinea-pig vas deferens by prostacyclin analogues.
AB  - 1. In the guinea-pig isolated vas deferens preparation bathed in Tyrode's
      solution, the prostacyclin analogues, cicaprost, TEI-9063, iloprost, taprostene
      and benzodioxane-prostacyclin, enhanced twitch responses to submaximal electrical
      field stimulation (20%-EFS). The high potency of cicaprost (EC150 = 1.3 nM) and
      the relative potencies of the analogues (equi-effective molar ratios = 1.0, 0.85,
      1.6, 17 and 82, respectively) suggest the involvement of a prostacyclin (IP-)
      receptor. 2. Maximum enhancement induced by cicaprost in 2.5 mM K+ Krebs
      Henseleit solution was similar to that in Tyrode solution (2.7 mM K+), but was
      progressively reduced as the K+ concentration was increased to 3.9, 5.9 and 11.9
      mM. There was also a greater tendency for the other prostacyclin analogues to
      inhibit EFS responses in 5.9 mM standard K+ Krebs-Henseleit solution; this may be
      attributed to their agonist actions on presynaptic EP3-receptors resulting in
      inhibition of transmitter release. 3. The EFS enhancing action of cicaprost was
      not affected by the alpha1-adrenoceptor antagonist prazosin (100 and 1000 nM).
      Cicaprost (20 and 200 nM) did not affect contractile responses of the vas
      deferens to either ATP (5 microM) or alpha,beta-methylene ATP (1 microM) in the
      presence of tetrodotoxin (TTX, 100 nM). In addition, enhancement by cicaprost of
      responses to higher concentrations of ATP (30 and 300 microM) in the absence of
      TTX, as shown previously by others, was not seen. Prostaglandin E2 (PGE2, 10 nM)
      and another prostacyclin analogue TEI-3356 (20 nM) enhanced purinoceptor agonist
      responses. Unexpectedly, TTX (0.1 and 1 microM) partially inhibited contractions
      elicited by 10-1000 microM ATP; contractions elicited by 1-3 microM ATP were
      unaffected. Further studies are required to establish whether a pre- or post
      synaptic mechanism is involved. 4. In a separate series of experiments, cicaprost
      (5-250 nM), TEI-9063 (3-300 nM), 4-aminopyridine (10-100 microM) and
      tetraethylammonium (100-1000 microM) enhanced both 20%-EFS responses and the
      accompanying overflow of noradrenaline to a similar extent. In further
      experiments with the EP1-receptor antagonist AH 6809, TEI-3356 (1.0-100 nM) and
      the EP3-receptor agonist, sulprostone (0.1-1.0 nM) inhibited both maximal EFS
      responses and noradrenaline overflow, thus confirming previous reports of the
      high activity of TEI-3356 at the EP3-receptor. Cicaprost had no significant
      effect on noradrenaline overflow at 10 and 100 nM, but produced a modest
      inhibition at 640 nM. 5. In conclusion, our studies show that prostacyclin
      analogues (particularly TEI-3356) can inhibit EFS responses of the guinea-pig vas
      deferens by acting as agonists at presynaptic EP3-receptors. Prostacyclin
      analogues (particularly cicaprost and TEI-9063) can also enhance EFS responses
      through activation of IP-receptors. The mechanism of the enhancement has not been
      rigorously established but from our results we favour a presynaptic action to
      increase transmitter release.

PMID- 9257923
TI  - Tolerance to mu-opioid agonists in human neuroblastoma SH-SY5Y cells as
      determined by changes in guanosine-5'-O-(3-[35S]-thio)triphosphate binding.
AB  - 1. The agonist action of morphine on membranes prepared from human neuroblastoma
      SH-SY5Y cells was measured by an increase in the binding of the GTP analogue
      [35S]-GTPgammaS. Morphine increased the binding of [35S]-GTPgammaS to SH-SY5Y
      cell membranes by 30 fmol mg(-1) protein with an EC50 value of 76 +/- 10 nM. 2.
      Incubation of SH-SY5Y cells with 10 microM morphine for 48 h caused a tolerance
      to morphine manifested by a 2.5 fold shift to the right in the EC50 value with a
      31 +/- 6% decrease in the maximum stimulation of [35S]-GTPgammaS binding. The
      response caused by the partial agonist pentazocine was reduced to a greater
      extent. 3. Chronic treatment of the cells with the more efficacious mu-ligand [D
      Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO, 10 microM) for 48 h afforded a greater
      effect than treatment with morphine. The maximal agonist effect of morphine was
      reduced to 58.9 +/- 6% of that seen in control cells while the maximal effect of
      DAMGO was reduced to 62.8 +/- 4%. There was a complete loss of agonist activity
      for pentazocine. 4. The development of tolerance was complete within 24 h and was
      blocked by naloxone and by the nonselective protein kinase inhibitor H7, but not
      by the putative beta-adrenoceptor kinase (beta-ARK) inhibitor suramin. 5. The
      observed tolerance effect was accompanied by a down-regulation of mu-opioid
      receptors determined by a decrease in the maximal binding capacity for the opioid
      antagonist [3H]-diprenorphine of 66 +/- 4%, but with no change in binding
      affinity. Binding of the agonist [3H]-DAMGO was similarly reduced. 6. The
      modulation of [35S]-GTPgammaS binding in SH-SY5Y cell membranes by opioids
      provides a simple method for the study of opioid tolerance at a site early in the
      signal transduction cascade.

PMID- 9257924
TI  - Properties of the pore-forming P2X7 purinoceptor in mouse NTW8 microglial cells.
AB  - 1. We have used whole-cell patch clamping methods to study and characterize the
      cytolytic P2X7 (P2Z) receptor in the NTW8 mouse microglial cell line. 2. At room
      temperature, in an extracellular solution containing 2 mM Ca2+ and 1 mM Mg2+, 2'-
      and 3'-O-(4-benzoylbenzoyl)-adenosine-5'-triphosphate (Bz-ATP; 300 microM), or
      ATP (3 mM), evoked peak whole cell inward currents, at a holding potential of -90
      mV, of 549 +/- 191 and 644 +/- 198 pA, respectively. Current-voltage
      relationships generated with 3 mM ATP reversed at 4.6 mV and did not display
      strong rectification. 3. In an extracellular solution containing zero Mg2+ and
      500 microM Ca2+ (low divalent solution), brief (0.5 s) application of these
      agonists elicited larger maximal currents (909 +/- 138 and 1818 +/- 218 pA, Bz
      ATP and ATP, respectively). Longer application of ATP (1 mM for 30 s) produced
      larger, slowly developing, currents which reached a plateau after approximately
      15-20 s and were reversible on washing. Under these conditions, in the presence
      of ATP, ethidium bromide uptake could be demonstrated. Further applictions of 1
      mM ATP produced rapid currents of the same magnitude as those observed during the
      30 s application. Subsequent determination of concentration-effect curves to Bz
      ATP, ATP and 2-methylthio-ATP yielded EC50 values of 58.3, 298 and 505 microM,
      respectively. These affects of ATP were antagonized by pyridoxal-phosphate-6
      azophenyl- 2', 4'-disulphonic acid (PPADS; 30 microM) but not suramin (100
      microM). 4. In low divalent solution, repeated application of 1 mM ATP for 1 s
      produced successively larger currents which reached a plateau, after 8
      applications, of 466% of the first application current. PPADS (30 microM)
      prevented this augmentation, while 5-(N,N-hexamethylene)-amiloride (HMA) (100
      microM) accelerated it such that maximal augmentation was observed after only one
      application of ATP in the presence of HMA. At a bath temperature of 32 degrees C,
      current augmentation also occurred in normal divalent cation containing solution.
      5. These data demonstrate that mouse microglial NTW8 cells possess a purinoceptor
      with pharmacological characteristics resembling the P2X7 receptor. We suggest
      that the current augmentation phenomenon observed reflects formation of the large
      cytolytic pore characteristic of this receptor. We have demonstrated that pore
      formation can occur under normal physiological conditions and can be modulated
      pharmacologically, both positively and negatively.

PMID- 9257925
TI  - Effects of captopril, losartan, and nifedipine on cell hypertrophy of cultured
      vascular smooth muscle from hypertensive Ren-2 transgenic rats.
AB  - 1. We hypothesized that tissular renin-angotensin system (RAS) induces vascular
      hypertrophy in hypertensive Ren-2 transgenic rats (TGR; strain name
      TGR(mRen2)L27). This assumption was tested in cell cultures of vascular smooth
      muscle (VSMC) from both hypertensive TGR and control normotensive Sprague-Dawley
      (SD) rats. Planar cell surface area, protein synthesis, and protein content per
      cell were studied, the role for locally produced angiotensin II (AII) was
      evaluated and the possible pharmacological interference by different drugs was
      analysed. 2. By use of radioimmunoassay techniques, AII could be determined in
      TGR cultures (10.25 +/- 0.12 pg per 10(7) cells) while it could not be detected
      in SD ones. 3. Under serum-free conditions, VSMC from hypertensive TGR were
      hypertrophic when compared to SD VSMC, as they presented a higher protein content
      per cell (335 +/-18 and 288 +/- 7 pg per cell respectively; P<0.05) and increased
      mean planar cell surface area, as determined by image analysis (4,074 +/- 238 and
      4,764 +/- 204 microm2, respectively; P < 0.05). 4. When exogenously added to
      cultured SD and TGR VSMC, AII (100 pM to 1 microM) promoted protein synthesis and
      protein content in a concentration-dependent manner without affecting DNA
      synthesis. Maximal effects were observed at 100 nM. At this concentration, AII
      effectively increased planar cell surface area in both SD and TGR cultures by
      approximately 20%. 5. Treatment of TGR cultures, in the absence of exogenous AII,
      with the angiotensin-converting enzyme inhibitor captopril or the angiotensin AT1
      receptors antagonist losartan (100 nM to 10 microM) reduced planar cell surface
      area in a concentration-dependent manner. In addition, both captopril and
      losartan (10 microM), decreased protein synthesis by approximately 15%. 6.
      Treatment of SD VSMC, in the absence of exogenous AII, with both captopril and
      losartan had no effect either on planar cell surface area or protein synthesis.
      7. Treatment with the Ca2+ antagonist nifedipine (100 nM to 10 microM) reduced
      cell size in both SD and TGR cultures. Maximal cell reduction reached by
      nifedipine averaged 906 +/- 58 and 1,292 +/- 57 microm2, in SD and TGR,
      respectively (P<0.05). In addition, nifedipine, nitrendipine and nisoldipine (all
      at 10 microM) decreased protein synthesis in both cell types by 15-25%. 8. We
      concluded that cultured VSMC from TGR are hypertrophic in comparison with those
      from SD. This cell hypertrophy can be the consequence of the expression of the
      transgene Ren-2 that activates a tissular RAS and locally produces AII, which
      acts in a paracrine, autocrine, or intracrine manner. Cell hypertrophy in TGR
      cultures could be selectively reduced by RAS blockade, while nifedipine decreased
      cell size and protein synthesis in both hypertrophic and non hypertrophic cells.

PMID- 9257926
TI  - Effects of extracellular pH on agonism and antagonism at a recombinant P2X2
      receptor.
AB  - 1. Under voltage-clamp conditions, the activity of agonists and antagonists at a
      recombinant P2X2 receptor expressed in Xenopus oocytes was examined at different
      levels of extracellular pH (pHe). 2. In normal Ringer (Mg2+ ions absent), the
      amplitude of submaximal inward currents to ATP was increased by progressively
      lowering pHe (8.0-5.5). ATP-responses reached a maximum at pH 6.5 with a 5 fold
      increase in ATP-affinity; the apparent pKa was 7.05 +/- 0.05. 3. Receptor
      affinity for ATP was lowered when extracellular Ca2+ ions were replaced with
      equimolar Mg2+ ions. However, the amplitude of the ATP-responses was still
      enhanced under acidic conditions, reaching maximal activity at pH 6.5 with a 5
      fold increase in ATP-affinity; the apparent pKa was 7.35 +/- 0.05. 4. ATP species
      present in the superfusate (for the above ionic conditions and pH levels) were
      calculated to determine the forms of ATP which activate P2X2 receptors: possible
      candidates include HATP, CaHATP and MgHATP. However, levels of these protonated
      species increase below pH 6.5, suggesting that receptor protonation rather than
      agonist protonation is more important. 5. The potency order for agonists of P2X2
      receptors was: ATP> 2-MeS-ATP ATPgammaS> ATPalphaS> >CTP >BzATP, while other
      nucleotides were inactive. EC50 and nH values for full agonists were determined
      at pH 7.4 and re-examined at pH 6.5. Extracellular acidification increased the
      affinity by approximately 5 fold for full agonists (ATP, 2-MeSATP, ATPyS and ATP
      alpha S), without altering the potency order. 6. The potency order for
      antagonists at P2X2 receptors was: Reactive blue-2 >trinitrophenol-ATP > or =
      Palatine fast black > or = Coomassie brilliant blue > or = PPADS>suramin (at pH
      7.4). IC50 values and slopes of the inhibition curves were re-examined at
      different pH levels. Only blockade by suramin was affected significantly by
      extracellular acidification (IC50 values: 10.4 +/- 2 microM, at pH 7.4; 78 +/- 5
      nM, at pH 6.5; 30 +/-6 nM, at pH 5.5). 7 In summary, a lowered pHe enhanced the
      activity of all agonists at P2X2 receptors but, with the exception of suramin,
      not antagonists. Since a lowered pHe is also known to enhance agonist activity at
      P2x receptors on sensory neurones containing P2X2 transcripts, the sensitization
      by metabolic acidosis of native P2x receptors containing P2X2 subunits may have a
      significant effect on purinergic cell-to-cell signalling.

PMID- 9257927
TI  - Resuscitating effect of melanocortin peptides after prolonged respiratory arrest.
AB  - 1. The resuscitating activity of melanocortin peptides (MSH-ACTH peptides) was
      tested in an experimental model of prolonged respiratory arrest. 2.
      Anaesthetized, endotracheally intubated rats subjected to a 5 min period of
      ventilation interruption, invariably died from cardiac arrest within 6-9 min of
      resumption of ventilation. 3. When resumption of ventilation was associated with
      the simultaneous intravenous (i.v.) injection of a melanocortin peptide (alpha
      MSH or ACTH-(1-24)) (160 microg kg(-1) there was an almost immediate (within 1
      min), impressive increase in cardiac output, heart rate, mean arterial pressure
      (+ 560% of the before-treatment value) and pulse pressure (+356% of the before
      treatment value), with full recovery of electroencephalogram after 30-45 min.
      Blood gases and pH were normalized within 15-60 min after treatment, and all
      treated animals eventually recovered completely and survived indefinitely (= more
      than 15 days). 4. The same response was observed in adrenalectomized animals, as
      well as in animals pretreated with a beta1-adrenoceptor blocking agent (atenolol,
      3 mg kg(-1), i.v.), or with an alpha1-adrenoceptor blocking agent (prazosin, 0.1
      mg kg(-1), i.v.), or with an adrenergic neurone blocking agent (guanethidine, 10
      mg kg(-1), intraperitoneally). 5. An effect quite similar to that produced by
      melanocortins was obtained with ouabain (0.1 mg kg(-1), i.v.); the antioxidant
      drug, glutathione (75 mg kg(-1), i.v.) also produced 100% resuscitation, but the
      effect was slower in onset. On the other hand, adrenaline (0.005 mg kg(-1), i.v.)
      was able to resuscitate only 1 out of 8 rats and dobutamine (0.02 mg kg(-1),
      i.v.) resuscitated 4 out of 8 rats; moreover, the effect of both catecholamines
      was much slower in onset than that of melanocortins and the initial, impressive
      stimulation of cardiovascular function was absent. 6. These results show that
      melanocortin peptides have a resuscitating effect in a pre-terminal condition
      produced in rats by prolonged asphyxia. This effect seems primarily due to the
      restoration of cardiac function, not mediated by catecholamines. These data also
      suggest that these peptides may have potential therapeutic value in conditions of
      transient cardiac hypoxia and re-oxygenation such as occur in coronary artery
      disease.

PMID- 9257928
TI  - Capsazepine block of voltage-activated calcium channels in adult rat dorsal root
      ganglion neurones in culture.
AB  - 1. We have found that capsazepine, a competitive antagonist at the vanilloid
      (capsaicin) receptor, blocks voltage-activated calcium currents in sensory
      neurones. 2. The block of calcium current was slow to develop with a half time of
      about one minute at 100 microM and lasted for the duration of the experiment. The
      rate of block of calcium current was strongly concentration-dependent. 3. The
      EC50 for the blocking effect at 0 mV was 7.7 +/- 1.4 microM after 6 min exposure
      to capsazepine. The EC50 at equilibrium was estimated to be 1.4 +/- 0.2 microM.
      4. The block of calcium current showed some voltage-dependence but there was no
      indication of any selectivity of action for a calcium channel subtype. The
      characteristics of the blocking action of capsazepine on the residual current of
      cells which were pretreated with either omega-conotoxin or nimodipine were
      similar to control. 5. The data suggest that capsazepine, in addition to its
      competitive antagonism of vanilloid receptors, has a non-specific blocking action
      on voltage-activated calcium channels which should be taken into account when
      interpreting the effects of this substance on intact preparations in vitro or in
      vivo.

PMID- 9257929
TI  - Effect of oxytocin as a partial agonist at vasoconstrictor vasopressin receptors
      on the human isolated uterine artery.
AB  - 1. The effect of oxytocin on endothelium-intact and endothelium-denuded segments
      of the human uterine artery rings was investigated. 2. In both types of
      preparation oxytocin induced contraction of human uterine artery with similar
      potency and efficacy (pEC50 values: 6.95 +/- 0.05 vs 7.06 +/- 0.01; maximal
      response values: 61 +/- 4.1% vs 63 +/- 5.1% for arteries with and without
      endothelium, respectively). 3. In contrast, human uterine arteries, both intact
      and denuded of endothelium, did not respond to the addition of the selective
      oxytocin receptor agonist, [Thr4, Gly7]oxytocin (10 nM(-1) microM). 4. The
      vasopressin receptor antagonists, [d(CH2)5Tyr(Me)]AVP (10-100nM) and [d(CH2)5,D
      Ile2,Ile4]AVP (300 nM-3 microM) produced parallel rightward shifts of the curves
      for oxytocin. The Schild plots constrained to a slope of unity gave the following
      -log K(B) values: [d(CH2)5Tyr(Me)] AVP vs [d(CH2)5,D-Ile2,Ile4] AVP 9.24 vs 6.91
      and 9.26 vs 6.84 for human uterine artery with intact and those denuded of
      endothelium, respectively. In contrast, in both types of preparations the
      oxytocin receptor antagonist, [d(CH2)5Tyr(OMe), 2Orn8]vasotocin (1 microM), did
      not significantly affect oxytocin-induced contractions. 5. The calculated pK(A)
      values for oxytocin itself also did not differ between preparations: 6.56 and
      6.43 for human uterine artery with and without endothelium, respectively. In both
      types of preparations, the receptor reserve (K(A)/EC50) was close to unity
      (intact vs denuded: 3.9 vs 3.0). 6. It is concluded that, in human uterine
      artery, oxytocin induces contractions that are not modulated by the endothelium.
      It is likely that oxytocin acts as a partial agonist on human uterine artery,
      regardless of the endothelial condition. On the basis of differential antagonists
      affinity and affinity of oxytocin itself, it is probable that receptors involved
      in oxytocin-induced contraction in human uterine arteries belong to the V(1A)
      vasopressin receptors.

PMID- 9257930
TI  - ACE inhibitor potentiation of bradykinin-induced venoconstriction.
AB  - 1. Angiotensin-converting enzyme (ACE) inhibitors exert their cardiovascular
      effects not only by preventing the formation of angiotensin II (AII), but also by
      promoting the accumulation of bradykinin in or at the vessel wall. In addition,
      certain ACE inhibitors have been shown to augment the vasodilator response to
      bradykinin, presumably by an interaction at the level of the B2 receptor. We have
      investigated whether this is a specific effect of the ACE inhibitor class of
      compounds in isolated endothelium-denuded segments of the rabbit jugular vein
      where bradykinin elicits a constrictor response which is exclusively mediated by
      activation of the B2 receptor. 2. Moexiprilat and ramiprilat (< or = 3 nM)
      enhanced the constrictor response to bradykinin three to four fold. Captopril and
      enalaprilat were less active by approximately one and quinaprilat by two orders
      of magnitude. Moexiprilat and ramiprilat, on the other hand, had no effect on the
      constrictor response to AII or the dilator response to acetylcholine. 3. The
      bradykinin-potentiating effect of the ACE inhibitors was not mimicked by
      inhibitors of amino-, carboxy-, metallo- or serine peptidases or the synthetic
      ACE substrate, hippuryl-L-histidyl-L-leucine, at a concentration which almost
      abolished the residual ACE activity in the vessel wall. In contrast, angiotensin
      (1-7) (10 microM), an angiotensin I metabolite, significantly enhanced the
      constrictor response to bradykinin. 4. Ramiprilat did not alter the binding of
      [3H]-bradykinin to a membrane fraction prepared from endothelium-denuded rabbit
      jugular veins or to cultured fibroblasts, and there was no ACE inhibitor
      sensitive, bradykinin-induced cleavage of the B2 receptor in cultured endothelial
      cells. 5. These findings demonstrate that ACE inhibitors selectively potentiate
      the B2 receptor-mediated vascular effects of bradykinin. Their relative efficacy
      appears to be independent of their ACE-inhibiting properties and might be related
      to differences in molecule structure. Moreover, the potentiation of the
      biological activity of bradykinin by this class of compounds does not seem to be
      mediated by a shift in affinity of the B2 receptor or a prevention of its
      desensitization, but may involve an increase in the intrinsic activity of
      unoccupied B2 receptor molecules.

PMID- 9257931
TI  - Regulation of the inducible cyclo-oxygenase pathway in human cultured airway
      epithelial (A549) cells by nitric oxide.
AB  - 1. In airway epithelium, nitric oxide (NO) is synthesized in the setting of
      inflammation by inducible nitric oxide synthase (iNOS). Although the role of
      epithelial derived NO in the regulation of human airways is unknown,
      prostaglandin E2 (PGE2) is recognised as an important inhibitory mediator in
      human airways. Cyclo-oxygenase (COX) is the rate limiting enzyme in the
      production of prostanoids and since inflammatory pathways enhance the expression
      of an inducible COX (COX-2), both COX-2 and iNOS may be co-expressed in response
      to an inflammatory stimulus. Although regulation of the COX-2 pathway by NO has
      been demonstrated in animal models, its potential importance in human airway
      epithelium has not been investigated. 2. The effect of endogenous and exogenous
      NO on the COX-2 pathway was investigated in the A549 human airway epithelial cell
      culture model. Activity of the COX-2 pathway was assessed by PGE2 EIA, and iNOS
      pathway activity by nitrite assay. A combination cytokine stimulus of interferon
      gamma (IFNgamma) 100 u ml(-1), interleukin-1beta (IL-1beta) 1 u ml(-1) and
      lipopolysaccharide (LPS) 10 microg ml(-1) induced nitrite formation which could
      be inhibited by the competitive NOS inhibitor N(G)-nitro-L-arginine-methyl-ester
      (L-NAME). IL-1beta alone (1-50 u ml(-1) induced PGE2 formation without
      significant nitrite formation, a response which was inhibited by the COX-2
      specific inhibitor nimesulide. Submaximal stimuli used for further experiments
      were IFNgamma 100 u ml(-1), IL-1beta 1 u ml(-1) and LPS 10 microg ml(-1) to
      induce both the iNOS and COX-2 pathways, and IL-1beta 3 u ml(-1) to induce COX-2
      without iNOS activity. 3. Cells treated with IFNgamma 100 u ml(-1), IL-1beta I u
      ml(-1) and LPS 10 microg ml(-1) for 48 h either alone, or with the addition of L
      NAME (0 to 10(-2) M), demonstrated inhibition by L-NAME of PGE2 (3.61 +/- 0.55 to
      0.51 +/- 0.04 pg/l0(4) cells; P<0.001) and nitrite (34.33 +/- 8.07 to 0
      pmol/10(4) cells; P<0.001) production. Restoration of the PGE2 response (0.187 +/
      0.053 to 15.46 +/- 2.59 pg/10(4) cells; P<0.001) was observed after treating
      cells with the same cytokine stimulus and L-NAME 10(-6) M, but with the addition
      of the NOS substrate L-arginine (0 to 10(-5) M). 4. Cells incubated with IL-1beta
      3 u ml(-1) for 6 h, either alone or with addition of the NO donor S-nitroso
      acetyl-penicillamine (SNAP) (0 to 10(-4) M), demonstrated increased PGE2
      formation (1.23 +/- 0.03 to 2.92 +/- 0.19 pg/10(4) cells; P< 0.05). No increase
      in PGE2 formation was seen when the experiment was repeated in the presence of
      the guanylate cyclase inhibitor methylene blue (50 microM). Cells treated with
      SNAP alone did not demonstrate an increased PGE2 formation. Cells incubated with
      IL-1beta 3 u ml(-1) for 6 h in the presence of dibutyryl cyclic guanylate
      monophosphate (0 to 10(-3) M) also demonstrated an increased PGE2 response (2.56
      +/- 0.21 to 4.53 +/- 0.64 pg/10(4) cells; P<0.05). 5. These data demonstrate that
      in a human airway epithelial cell culture system, both exogenous and endogenous
      NO increase the activity of the COX-2 pathway in the setting of inflammatory
      cytokine stimulation, and that this effect is likely to be mediated by guanylate
      cyclase. This suggests a role for NO in the regulation of human airway
      inflammation.

PMID- 9257932
TI  - Pharmacological properties of the Ca2+-release mechanism sensitive to NAADP in
      the sea urchin egg.
AB  - 1. The sea urchin egg homogenate is an ideal model to characterize Ca2+-release
      mechanisms because of its reliability and high signal-to-noise-ratio. Apart from
      the InsP3- and ryanodine-sensitive Ca2+-release mechanisms, it has been recently
      demonstrated that this model is responsive to a third independent mechanism, that
      has the pyridine nucleotide, nicotinic acid adenine dinucleotide phosphate
      (NAADP), as an endogenous agonist. 2. The sea urchin egg homogenate was used to
      characterize the pharmacological and biochemical characteristics of the novel
      Ca2+-releasing agent, NAADP, compared to inositol trisphosphate (InsP3) and
      cyclic ADP ribose (cyclic ADPR), an endogenous activator of ryanodine receptors.
      3. NAADP-induced Ca2+-release was blocked by L-type Ca2+-channel blockers and by
      Bay K 8644, while InsP3- and cyclic ADPR-induced Ca2+-release were insensitive to
      these agents. L-type Ca2+-channel blockers did not displace [32P]-NAADP binding,
      suggesting that their binding site was different. Moreover, stopped-flow kinetic
      studies revealed that these agents blocked NAADP in a all-or-none fashion. 4.
      Similarly, a number of K+-channel antagonists blocked NAADP-induced Ca2+-release
      selectively over InsP3- and cyclic ADPR-induced Ca2+-release. Radioligand studies
      showed that these agents were not competitive antagonists. 5. As has been shown
      for InsP3 and ryanodine receptors, NAADP receptors were sensitive to calmodulin
      antagonists, suggesting that this protein could be a common regulatory feature of
      intracellular Ca2+-release mechanisms. 6. The presence of K+ was not essential
      for NAADP-induced Ca2+-release, since substitution of K+ with other monovalent
      cations in the experimental media did not significantly alter Ca2+ release by
      NAADP. On the contrary, cyclic ADPR and InsP3-sensitive mechanisms were affected
      profoundly, although to a different extent depending on the monovalent cation
      which substituted for K+. Similarly, modifications of the pH in the experimental
      media from 7.2 to 6.7 or 8.0 only slightly affected NAADP-induced Ca2+-release.
      While the alkaline condition permitted InsP3 and cyclic ADPR-induced Ca2+
      release, the acidic condition completely hampered both Ca2+-release mechanisms.
      7. The present results characterize pharmacologically and biochemically the novel
      Ca2+-release mechanism sensitive to NAADP. Such characterization will help future
      research aimed at understanding the role of NAADP in mammalian systems.

PMID- 9257933
TI  - Effects of [3H]-BIDN, a novel bicyclic dinitrile radioligand for GABA-gated
      chloride channels of insects and vertebrates.
AB  - 1. The radiolabelled bicyclic dinitrile, [3H]-3,3-bis-trifluoromethyl
      bicyclo[2.2.1]heptane-2,2-dicarbonitrile  ([3H]-BIDN), exhibited, specific
      binding of high affinity to membranes of the southern corn rootworm (Diabrotica
      undecimpunctata howardi) and other insects. A variety of gamma-aminobutyric acid
      (GABA) receptor convulsants, including the insecticides heptachlor (IC50, 35 +/-
      3 nM) and dieldrin (IC50, 93 +/- 7 nM), displaced [3H]-BIDN from rootworm
      membranes. When tested at 100 microM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7
      trioxabicyclo[2.2.2]oct ane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicy
      clo[2.2.2]octane-1-thio ne (TBPS), 1-phenyl-4-t-butyl-2,6,7
      trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [3H]
      BIDN binding to rootworm membranes indicating that the bicyclic dinitrile
      radioligand probes a site distinct from those identified by other convulsant
      radioligands. 2. Dissociation studies showed that dieldrin, ketoendrin,
      toxaphene, heptachlor epoxide and alpha and beta endosulphan displace bound [3H]
      BIDN from rootworm membranes by a competitive mechanism. 3. Rat brain membranes
      were also shown to possess a population of saturable, specific [3H]-BIDN binding
      sites, though of lower affinity than in rootworm and with a different
      pharmacological profile. Of the insecticidal GABAergic convulsants that displaced
      [3H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain
      membranes, many were more effective in rootworm. 4. Functional GABA-gated
      chloride channels of rootworm nervous system and of cockroach nerve and muscle
      were blocked by BIDN, whereas cockroach neuronal GABA(B) receptors were
      unaffected. 5. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA
      derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in
      the nervous system of Drosophila melanogaster resulted in functional, homo
      oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel
      site on GABA-gated Cl- channels to which a number of insecticidally-active
      molecules bind.

PMID- 9257935
TI  - Electrophysiological properties of the human N-type Ca2+ channel: I. Channel
      gating in Ca2+, Ba2+ and Sr2+ containing solutions.
AB  - We have characterized the properties of the human N-type Ca2+ channel produced by
      the stable co-expression of the alpha(1B-1), alpha(2b)delta and beta(1b)
      subunits. The channel displayed the expected pharmacology with respect to the
      toxins omega-CTx-GVIA and omega-CTx-MVIIC, which depressed currents in a voltage
      independent fashion. We characterized a variety of biophysical properties of the
      channel under conditions in which either Ca2+, Ba2+ or Sr2+ was the sole
      extracellular divalent ion. In all three ions, current-voltage relationships
      revealed that the channel was clearly high-voltage activated. Current activation
      was significantly slower in Ca2+ than either Sr2+ or Ba2+. Construction of
      conductance-voltage relationships from tail current measurements indicated that
      the channel was more high-voltage activated in Ca2+ than in either Sr2+ or Ba2+.
      The rank order of current amplitude at +4 mV was Ba2+ > Sr2+ > or = Ca2+.
      Elevation of the extracellular concentration of Ba2+ increased maximal current
      amplitude and shifted the current-voltage relationship to the right. In all three
      ions channel inactivation was complex consisting of three distinct exponentials.
      Recovery from inactivation was slow taking several seconds to reach completion.
      Steady-state inactivation curves revealed that channel inactivation became
      detectable at holding potentials of between -101 and -91 mV depending on the
      permeating species. The rank order of mid-points of steady state inactivation was
      (most negative) Sr2+ > Ca2+ > Ba2+ (most positive). Deactivation of the N-type
      Ca2+ channel was voltage-dependent and very fast in all three ions. The
      deactivation rate in Ba2+ was significantly slower than that in both Ca2+ and
      Sr2+, however the voltage-dependence of deactivation rate was indistinguishable
      in all three ions.

PMID- 9257934
TI  - Contrasting biophysical and pharmacological properties of T-type and R-type
      calcium channels.
AB  - In contrast to other kinds of voltage-gated Ca2+ channels, the underlying
      molecular basis of T-type and R-type channels is not well-understood. To
      facilitate comparisons with cloned Ca2+ channel subunits, we have carried out a
      systematic analysis of the properties of T-type currents in undifferentiated
      NG108-15 cells and R-type currents in cerebellar granule neurons. Marked
      differences were found in their biophysical and pharmacological features under
      identical recording conditions. T-type channels became activated at potentials
      approximately 25 mV more negative than R-type channels; however, T-type channels
      required potentials approximately 15 mV less negative than R-type channels to be
      available. Accordingly, T-type channels display a much larger overlap between the
      curves describing inactivation and activation, making them more suitable for
      generating sustained Ca2+ entry in support of secretion or pacemaker activity. In
      contrast, R-type channels are not equipped to provide a steady current, but are
      very capable of supplying transient surges of Ca2+ influx. In response to a
      series of increasingly strong depolarizations T-type and R-type Ca2+ channels
      gave rise to very different kinetic patterns. T-type current records crossed each
      other in a characteristic pattern not found for R-type currents. These
      biophysical distinctions were independent of absolute membrane potential and
      were, therefore, complementary to the conventional categorization of T- and R
      type Ca2+ channels as low- and high-voltage activated. R-type channels
      deactivated approximately eight-fold more quickly than T-type channels, with
      clear consequences for the generation of divalent cation influx during simulated
      action potentials. Pharmacological comparisons revealed additional contrasts. R
      type current was responsive to block by omega-Aga IIIA but not nimodipine, while
      the opposite was true for T-type current. Both channel types were potently
      inhibited by the non-dihydropyridine compound mibefradil. In all respects
      examined, R-type currents were similar to currents derived from expression of the
      alpha1E subunit whereas T-type currents were not.

PMID- 9257936
TI  - Cloning and stable expression of the mGluR1b subtype of human metabotropic
      receptors and pharmacological comparison with the mGluR5a subtype.
AB  - We isolated and characterized a cDNA encoding the human metabotropic glutamate
      receptor subtype 1b (hmGluR1b). In situ hybridization studies in human brain
      regions revealed a higher distribution of mGluR1 mRNA in the dentate gyrus of the
      hippocampus, the substantia nigra pars compacta and the Purkinje cell layer of
      the cerebellum compared to other regions studied. We established stable
      expression of recombinant hmGluR1b in L(tk-) mouse fibroblast and Chinese hamster
      ovary (CHO-dhfr-) cells. In both expression systems, agonist activation of
      hmGluR1b stimulated inositol phosphate (InsP) formation and elevation of the
      cytosolic free calcium ([Ca2+]i), and both responses were blocked by (S)-MCPG.
      The rank order of potency for agonists was quisqualate > glutamate > (1S,3R)-ACPD
      in both expression systems. Comparison of the agonist profiles of hmGluR1b and
      hmGluR5a, both stably expressed in L(tk-) cells, indicated the same rank order of
      potency (quisqualate > glutamate > or = (RS)-3,5-DHPG > or = (1S,3R)-ACPD), but
      each of the four agonists were more potent on hmGluR5a than on hmGluR1b. In
      antagonist studies, (S)-MCPG inhibited the agonist-induced InsP formation and
      elevation of [Ca2+]i in both hmGluR1b- and hmGluR5a-expressing cells. (S)-4CPG
      and (S)-4C3HPG both inhibited agonist responses only in hmGluR1b-expressing
      cells. However, in hmGluR5a-expressing cells the antagonist activity of (S)-4CPG
      and (S)-4C3HPG was dependent on the agonist used in the study, since they
      inhibited responses to glutamate but not to quisqualate. Stable cell lines
      expressing specific subtypes of human mGluRs represent valuable tools for the
      study of the mechanism of action of mGluRs at the molecular and cellular level
      and as screening targets for identification of subtype-selective agonists or
      antagonists.

PMID- 9257937
TI  - Pharmacological characterization of metabotropic glutamate receptors linked to
      the inhibition of adenylate cyclase activity in rat striatal slices.
AB  - The pharmacological profile of mGlu receptors negatively linked to adenylyl
      cyclase was characterized in adult rat striatal slices. Among the mGlu agonists
      tested, (+)-2-aminobicyclo-[3.1.0]-hexane-2,6-di carboxylate (LY354740), was the
      most potent inhibitor of forskolin-stimulated cAMP formation (EC50 = 11 +/- 2
      nM). Inhibition of forskolin stimulation by the group III agonist L-2-amino-4
      phosphono-butanoate (L-AP4) was biphasic, the two parts of the concentration
      curve having EC50 values of 6 +/- 1 microM and 260 +/- 4 microM, suggesting a
      sequential recruitment of mGlu4/8 and mGlu7. The effects of several new
      phenylglycine derivative antagonists were tested on the inhibition of forskolin
      cAMP response by (2S,1'S,2'S)-2-(carboxy-cyclopropyl)-glycine (L-CCG I) and L
      AP4. At 500 microM, (RS)-alpha-methyl-3-carboxy-methyl-pheny lglycine was unable
      to antagonize the effect of L-CCG I or L-AP4 but (S)-alpha-methyl-3-carboxy
      phenylalanine inhibited the effect of L-AP4 with a low potency. Finally, (RS)
      alpha-methyl-4-tetrazolylphenylglyc ine and particularly (RS)-alpha-methyl-4
      phosphonophenylglyci ne, appeared to be the most potent and selective antagonists
      of L-AP4 induced inhibition of forskolin-stimulated cAMP production in adult rat
      striatal slices.

PMID- 9257939
TI  - Electrophysiological effects of the anticonvulsant remacemide hydrochloride and
      its metabolite ARL 12495AA on rat CA1 hippocampal neurons in vitro.
AB  - The electrophysiological actions of the putative anticonvulsants remacemide
      hydrochloride and its des-glycine metabolite ARL 12495AA were examined using
      whole-cell recordings from CA1 hippocampal neurons in adult rat brain in vitro.
      Remacemide hydrochloride (4-400 microM) and ARL 12495AA (4-400 microM) limited
      sustained high frequency repetitive firing (SRF) induced by application of long
      duration depolarizing current pulses (20-400 pA, 500 msec). This SRF limitation
      was concentration-dependent, and equipotent IC50 values of 66 and 60 microM were
      calculated for remacemide hydrochloride and ARL 12495AA, respectively.
      Examination of the spike configuration revealed that, over the same concentration
      range, each compound caused a concentration-related reduction of: (a) the action
      potential amplitude; and (b) the rate-of-rise. Remacemide hydrochloride or ARL
      12495AA increased spike duration and decreased or eliminated the spike after
      hyperpolarization. Possible mechanisms for these electrophysiological actions
      including modulation of sodium and/or potassium channel activity are considered.
      It is suggested that such multiple mechanisms, including inhibition of SRF may be
      relevant to the anticonvulsant properties of remacemide hydrochloride and its
      metabolite, ARL 12495AA. The activity of both compounds as modulators of neuronal
      excitability indicates that metabolic conversion of remacemide hydrochloride to
      ARL 12495AA could enhance the therapeutic efficacy of the former.

PMID- 9257940
TI  - Uncompetitive NMDA receptor antagonists attenuate NMDA-induced impairment of
      passive avoidance learning and LTP.
AB  - In general, N-methyl-D-aspartate (NMDA) receptor antagonists inhibit learning and
      long term potentiation (LTP). However, it has been suggested that direct tonic,
      i.e. non-temporal, activation of NMDA receptors, in contrast to learning, may
      lead to an increase in synaptic "noise" and, in turn, to a loss of association
      detection. In the present study, a two-choice passive avoidance task and LTP in
      vitro (CA1 hippocampal region) were used to address this issue. Dark avoidance
      learning was impaired by systemic NMDA administration (starting at 25 mg/kg) that
      was not related to either toxic effects or state-dependent learning. NMDA-induced
      amnesia was antagonized by ((+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10
      imine maleate (MK-801) and 1-amino-3,5-dimethyladamantane (memantine), starting
      at low doses of 0.05 and 2.5 mg/kg, respectively, in a bell-shaped dose-response
      relationship. A competitive NMDA receptor antagonist CGP-39551 failed to reverse
      NMDA-induced amnesia. In hippocampal slices, NMDA (10 microM) depressed (S)-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolproprionic acid (AMPA) receptor-mediated field
      potentials in CA1 and also caused a moderate reduction of LTP
      induction/expression. It was this latter effect that was antagonized by memantine
      (1 microM). Thus, under conditions of tonic activation of NMDA receptors,
      uncompetitive NMDA receptor antagonists can paradoxically reverse deficits in
      learning and synaptic plasticity.

PMID- 9257938
TI  - Alpha subunit isoform influences GABA(A) receptor modulation by propofol.
AB  - We have investigated the role of the alpha subunit in the modulation of gamma
      aminobutyric acid type A (GABA(A)) receptors by the general anesthetic propofol,
      using whole-cell patch clamp recordings made from distinct stable fibroblast cell
      lines which expressed only alpha1beta3gamma2 or alpha6beta3gamma2 GABA(A)
      receptors. At clinically relevant anesthetic concentrations, propofol potentiated
      submaximal GABA currents in alpha1beta3gamma2 receptors to a far greater degree
      than those in alpha6beta3gamma2 receptors. The alpha subunit influenced the
      efficacy of propofol for modulation, but not its potency. In contrast, direct
      gating of the ion channel by propofol, in the absence of GABA, was significantly
      larger in the alpha6 than the alpha1 containing receptors. The potentiation of
      submaximal GABA by trichloroethanol, and the potentiation and direct gating by
      methohexital was also studied, and showed the same relative trends as propofol.

PMID- 9257941
TI  - Changes in protein synthesis and synthesis of the synaptic vesicle protein,
      synaptophysin, in entorhinal cortex following induction of long-term potentiation
      in dentate gyrus: an age-related study in the rat.
AB  - We have examined protein synthesis in entorhinal cortex following induction of
      long-term potentiation (LTP) in perforant path-granule cell synapses. The data
      presented here indicate that there was an increase in [35S]methionine labelling
      of TCA-precipitated proteins and [35S]methionine labelling of synaptophysin in
      the ipsilateral entorhinal cortex 40 min after induction of LTP in dentate gyrus.
      Intraventricular injection of both the NMDA antagonist, D-amino
      phosphonovalerate, and the protein synthesis inhibitor, anisomycin reduced
      protein synthesis though the decrease caused by anisomycin was much more
      profound. Both agents blocked induction of LTP and the increase in protein
      synthesis and synaptophysin synthesis which accompanied LTP. These data indicate
      a close coupling of increased protein synthesis in the entorhinal cortex and
      expression of LTP in the dentate gyrus. This coupling was further suggested by
      the absence of an LTP-associated increase in protein synthesis in aged animals,
      in which LTP was markedly attenuated. The possibility that these changes impact
      on morphological changes which accompany LTP is discussed.

PMID- 9257942
TI  - The effects of metabolic stress on glutamate receptor-mediated depolarizations in
      the in vitro rat hippocampal slice.
AB  - A grease-gap preparation for the in vitro rat hippocampal slice has been used to
      record field excitatory postsynaptic potentials (fEPSPs), extracellular d.c.
      potential and depolarizations in response to glutamate receptor agonists before,
      during and after hypoxic/ischaemic episodes in the CA1 region. Synaptic
      transmission was depressed by hypoxia in a temperature-dependent manner (t1/2 at
      28 degrees C, 1.9 +/- 0.2 min; t1/2 at 36 degrees C, 1.0 +/- 0.1 min) but was
      unaffected by the absence of D-glucose during hypoxia (ischaemia) at 28 degrees
      C. The reappearance of the fEPSP during hypoxic/ischaemic episodes was a prelude
      to severe disruptions of synaptic transmission if control conditions were not
      reinstated within 1 min of the secondary depression of the fEPSP. For a 10 min
      episode of hypoxia, recovery of synaptic transmission at 28 degrees C (96 +/-
      1.5% of control) was significantly better than recovery following either hypoxia
      at 36 degrees C or ischaemia at 28 degrees C (41 +/- 17.2% and 55 +/- 21% of
      control, respectively). Chart recordings of the d.c. potential during hypoxia
      revealed a predominate (67% of all episodes) triphasic sequence of events (i,
      hyperpolarization; ii, depolarization; iii, post-hypoxic hyperpolarization on
      reoxygenation). Depolarizing responses to N-methyl-D-aspartate (NMDA, 20-40
      microM; in 1 mM extracellular Mg2+), alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA, 2-10 microM) and L-glutamate (L-Glu, 2-5 mM) could be
      elicited at times when fEPSPs were completely depressed and up to 20 min into a
      hypoxic episode, the latest time-point examined. This implies, as others have
      suggested, that the hypoxic depression of excitatory synaptic transmission is
      presynaptic in origin. The application of AMPA or NMDA during the hypoxic
      depression of the fEPSP occasionally resulted in a short-lasting (12-45 min)
      potentiation (117-143% of control) of the fEPSP on return to normoxia.
      Furthermore, in other slices, which were exposed to severe metabolic stress,
      synaptic transmission was depressed to a significantly greater extent than AMPA
      depolarizations (mean depression; 76 +/- 5% and 28 +/- 8%, respectively).

PMID- 9257943
TI  - Mechanism of the hypothermic effect of MPP+ administered centrally in mice.
AB  - The neurotoxin methyl phenyl pyridinium (MPP+) was administered
      intracerebroventricularly (i.c.v.) to mice. From the 1.25 microg dose per mouse,
      MPP+ elicited a dose-dependent hypothermic effect from doses as low as 1.25
      microg per mouse. The minimal lethal dose was determined to be between 17.5 and
      20 microg per mouse. The hypothermia induced by 2.5 microg MPP+ was unaffected by
      pretreatment with propranolol (8 mg/kg, i.p.), scopolamine (5 mg/kg, s.c.) and
      haloperidol (250 microg/kg, i.p.). It was decreased by yohimbine (4 mg/kg, s.c.),
      idazoxan (5 mg/kg, s.c.) and desipramine (20 mg/kg, i.p.). In mice injected
      i.c.v. with 6 hydroxydopamine (50 microg, 8 days before testing with MPP+ 2.5
      microg), a significant reduction in the hypothermic effect of MPP+ was observed.
      A similar 6 OHDA injection has been shown previously to reduce by about 40% the
      DA striatal content of DA and by about 70% the hypothalamic content of NE. On the
      contrary, in mice injected with MPP+ (17.5 microg, 8 days before testing with 50
      microg 6 OHDA) there was no modification in the hypothermic effect of 6 OHDA (50
      microg). This injection of MPP+ reduced by about 40% the striatal content of DA
      but did not affect the hypothalamic content of NE. It is concluded that MPP+
      decreases body temperature, at least in part, by acting as an indirect NE
      agonist, which stimulates alpha2 adrenoreceptors. In contrast, this agent in the
      present experimental conditions, does not destroy NE neurons in opposition to its
      action on DA neurons.

PMID- 9257944
TI  - Characterization of [125I]S(-)5-OH-PIPAT binding to dopamine D2-like receptors
      expressed in cell lines.
AB  - Recently, [125I]S(-)5-OH-PIPAT [5-hydroxy-2-(N-n-propyl-N-3'-iodo-2'
      propenyl)aminotetralin], a derivative of S(-)5-OH-DPAT (5-hydroxy-N,N-di-n-propyl
      aminotetralin), was reported to be a better radioiodinated dopamine D2-like
      receptor ligand than the previously reported iodinated ligand, [125I]R(+)7-OH
      PIPAT. Therefore, in the present study, the binding profile of [125I]S(-)5-OH
      PIPAT to D2-like receptors expressed in cell lines was established. High binding
      affinity (Kd = 0.3-0.4 nM) and NaCl sensitivity were displayed with this ligand
      in membranes of human embryonic kidney (HEK293) cells expressing either human D2
      or rat D3 receptors and in Chinese hamster ovary (CHO) cells expressing human
      dopamine D4 receptors. Specific binding to D2 and D4 receptors was significantly
      increased in the presence of 2 mM MgCl2 and decreased in the presence of 100
      microM 5'-guanylyl-imidodiphosphate (GMP-PNP). This finding is consistent with
      reports that 2-aminotetralin compounds display agonist properties. The specific
      binding to D3 receptors however, was not affected by either MgCl2 or GMP-PNP.
      This lack of GMP-PNP sensitivity for D3 receptors may result from inadequate G
      protein-receptor coupling in this cell line. The rank order of potency for
      inhibition of [125I]S(-)5-OH-PIPAT binding with various dopamine agents was
      consistent with reported values for D2, D3 and D4 receptors. In membranes
      prepared from Spodoptera frugiperda (Sf9) cells infected with baculovirus that
      contains DNA encoding D3 receptors, [125I]S(-)5-OH-PIPAT recognized only 70% of
      the receptor population labeled by [125I]NCQ298. This new ligand offers several
      unique advantages, including high specific activity, high binding affinity and
      selectivity for D2-like receptors, that make it an excellent probe for the
      investigation and the characterization of dopamine D2-like receptors.

PMID- 9257945
TI  - Expression of B1 and B2 bradykinin receptor mRNA and their functional roles in
      sympathetic ganglia and sensory dorsal root ganglia neurones from wild-type and
      B2 receptor knockout mice.
AB  - Bradykinin has been implicated in nociception and inflammation. To examine the
      relative significance of B1 and B2 bradykinin receptor subtypes in sympathetic
      and sensory ganglia, the electrophysiological effects of bradykinin analogues and
      the expression of receptor subtype mRNA were examined in wild-type and "B2
      knockout" mice from which the B2 receptor gene had been deleted. In wild-type
      mice the B2 receptor agonist bradykinin depolarized superior cervical ganglia
      (SCG) and activated inward currents in dorsal root ganglia (DRG) neurones.
      Responses to the B1 receptor agonist, [des-Arg10]-kallidin, were seen only in SCG
      that had been pre-treated with interleukins and the peptidase inhibitor
      captopril, but not in DRG neurones. The up-regulation of responses to [des-Arg10]
      kallidin and substance P were blocked by indomethacin and, thus, were dependent
      upon cyclo-oxygenase activity. The effects of bradykinin were abolished in SCG
      and DRG's from B2 knockout mice and this was correlated with the absence of B2
      receptor mRNA in ganglia from these animals. However, despite the presence of B1
      receptor mRNA in interleukin treated SCG from B2 knockout mice, no depolarizing
      effects of the B1 receptor agonist [des-Arg10]-kallidin were observed. The
      successful elimination of bradykinin responses and B2 mRNA in sympathetic and
      sensory ganglia from B2 knockout mice, confirms that B2 receptors are the
      predominant functional bradykinin receptor subtype in these tissues and that B1
      receptor mRNA is expressed in both sympathetic and sensory ganglia from these
      animals.

PMID- 9257946
TI  - Processing of mycobacterial lipids and effects on host responsiveness.
AB  - One of the most important opportunistic pathogens associated with AIDS is the
      Mycobacterium avium complex. M. avium infections are found in up to 70% of
      individuals in advanced stages of AIDS. The deficiency in our knowledge of these
      mycobacteria presents an obstacle to the development of a rational approach for
      controlling these life-threatening infections in immunocompromised persons. It is
      apparent that M. avium can replicate in host macrophages and persist for long
      periods. During this time, various components, particularly lipids, accumulate in
      host macrophages and contribute to the ability of this organism to upset the
      cytokine homeostasis necessary for controlling infections of this type. M. avium
      lipids are immunosuppressive and can induce a variety of cytokines and
      eicosanoids that affect general host responses. The intention of this review is
      to examine the postphagocytic processing of various M. avium lipids with respect
      to their ability to alter host responses, particularly in immunocompromised
      patients such as those infected with HIV.

PMID- 9257948
TI  - Coxsackieviruses and pancreatitis.
AB  - While alcohol abuse and biliary disease can result in the development of
      pancreatitis, the factors that contribute to the idiopathic form of the disease
      are not well understood. I propose that coxsackievirus infections account for a
      subset of cases of pancreatitis of unknown etiology. Evidence to support this
      concept is derived from serological studies, case reports and animal models. In
      reviewing the available data, it is obvious that the relationship between
      coxsackievirus infection and the development of pancreatitis is not a simple one.
      Many elements contribute to the development of the disease including the strain
      of the infecting virus, the genetic predisposition of the host and additional
      environmental factors that maintain the disease process. Studies that show an
      association between coxsackievirus infection and acute pancreatitis in humans are
      given additional support by the extensive data from mouse studies demonstrating
      that some serotypes (B4,B3) are tropic for the exocrine pancreas. Some viral
      strains may cause limited pancreatic tissue injury which is compatible with
      tissue repair followed by full restoration of pancreatic function. Other viral
      strains may cause more extensive tissue damage giving rise to chronic
      pancreatitis which, on a genetic background that predisposes to autoimmunity, may
      result in an autoimmune chronic pancreatitis. A multi-disciplinary approach is
      required to increase our understanding of the complex relationship between
      coxsackievirus infection and pancreatic diseases. Such studies should address the
      biology of viral replication, the immune response to infection, the role of
      viruses in the development of autoimmunity, the biology of pancreatic tissue
      injury and the underlying repair process.

PMID- 9257947
TI  - Oral antibiotics in the nineties: new drugs and new challenges in primary care.
AB  - The primary care physician is faced with a bewildering array of new oral
      antimicrobials to treat common infections. These agents promise to be extremely
      effective as replacements for time-honored drugs, as prophylaxis, and for the
      treatment of infections previously requiring prolonged intravenous therapy. The
      overuse of the newer macrolides, quinolones, and beta-lactam beta-lactamase
      inhibitors may prove to be ecologically and economically costly. It is feared
      that the selective pressure from these broad spectrum agents may burden society
      with an even greater problem of multiply resistant community-acquired pathogens.
      The specific therapeutic and economic advantages and disadvantages of each class
      should be considered and the decision to employ these agents should be highly
      individualized.

PMID- 9257949
TI  - Genetic mapping of the gene encoding cysteine string protein.

PMID- 9257950
TI  - Interpretation of the literature on endoscopic hemostasis.
AB  - This article discusses the essential features of a well-designed clinical
      therapeutic trial to aid the clinician in his or her interpretation of the large
      number of papers available on the subject of endoscopic hemostasis. A thorough
      understanding of the variations in the study methodology can then be used to
      select the highest quality studies of endoscopic hemostasis for use in their
      practice.

PMID- 9257963
TI  - Imaging of the elbow. An update.
AB  - This article focuses on the use of magnetic resonance in the evaluation of the
      soft tissue (tendons, ligaments, muscles, and nerves) and osseous structures of
      the elbow. The need for high quality, high resolution imaging with attention to
      positioning, sequence selection, and equipment is emphasized. Normal magnetic
      resonance anatomy and criteria for pathologic change are presented.

PMID- 9257962
TI  - A practical approach to imaging of the shoulder with emphasis on MR imaging.
AB  - Our understanding of shoulder disorders has changed considerably as a result of
      improved diagnostic tools, such as arthroscopy and multiplanar imaging
      modalities. The diagnosis of the cause of shoulder pain can be difficult because
      a spectrum of disorders, including cervical spine disease, acromioclavicular
      arthritis, and shoulder instability. Impingement and denervation syndromes can
      present with similar clinical findings. Accurate depiction of anatomic
      abnormalities is important for treatment planning. The purpose of this article is
      to report on the application of available imaging modalities, with emphasis on MR
      imaging. A strategy for the appropriate use of these studies and their variations
      of technique is also provided.

PMID- 9257964
TI  - Imaging of the hand and wrist.
AB  - This article reviews many of the most commonly used modalities for imaging the
      hand and wrist. Particular attention is paid to proper radiographic positioning,
      with emphasis on the four-view wrist series. Standard wrist measurements are
      detailed, and wrist arthrography is also discussed. Techniques for cross
      sectional imaging, computed tomography, and MR imaging are reviewed, and several
      examples are presented as to where MR imaging is diagnostically valuable.

PMID- 9257965
TI  - Imaging of the spine. Techniques of MR imaging.
AB  - Recently, magnetic resonance (MR) imaging has become the preferred method of
      evaluation for spinal disorders. The vertebrae, intervertebral disks, ligaments,
      spinal canal, and neural foramen may all be evaluated using current MR imaging
      techniques. MR imaging with paramagnetic contrast has developed into a valuable
      technique for diagnosing a tumor, an infection, or a degenerative disease.
      Computed tomography remains the procedure of choice for examining fine cortical
      bone detail including evaluation of spine fractures and assessing neural
      foraminal size, but it is not sensitive for detecting marrow-infiltrating
      disorders.

PMID- 9257967
TI  - Imaging of the knee. Current status.
AB  - This article reviews the variety of imaging modalities that are currently being
      used to evaluate the knee. Nuclear scintigraphy is discussed with emphasis on
      prosthesis abnormalities. Sonography is discussed with regard to the evaluation
      of popliteal masses. The uses of computed tomography, especially in the
      evaluation of the tibial plateau fracture, are discussed, and the role of
      fluoroscopy, computed tomography, and sonography in image-guided needle
      procedures are reviewed. Emphasis is placed on the role of MR imaging in knee
      imaging, with attention to internal derangements, bursal and capsular pathology,
      and other assorted intra- and extra-articular disorders. The focus of this
      article is to review the wealth of information that may be obtained by using
      these imaging modalities.

PMID- 9257966
TI  - Current concepts in imaging of the pelvis and hip.
AB  - Over the past decade, imaging evaluation of orthopedic conditions of the pelvis
      and hips has become increasingly complex. Although the conventional radiograph
      remains the initial examination of choice, the decision between secondary tests,
      such as computed tomography, MR imaging, or scintigraphy is far from clear. A
      thorough understanding of current imaging technology is necessary for the
      clinician to choose the most appropriate examination for a given situation. This
      article reviews the current status of orthopedic imaging in the areas of acute
      trauma, stress injuries, osteonecrosis, arthropathies, tumors, and interventional
      imaging.

PMID- 9257968
TI  - MR imaging of the symptomatic ankle and foot.
AB  - MR imaging can play a key role in the evaluation of soft tissues and marrow space
      of the symptomatic muscle and foot. Diagnostic efficacy is optimized by tailoring
      the examination to a given problem. Techniques for MR imaging of the foot and
      ankle are reviewed, the clinical use of MR imaging for examining the structures
      of the foot and ankle is discussed, and strategies for the integration of MR
      imaging into the work-up of selected clinical problems are presented.

PMID- 9257969
TI  - Development and validation of a satellites based geographic information system
      (GIS) model for epidemiology of Schistosoma risk assessment on snail level in
      Kafr El-Sheikh Governorate.
AB  - The aim of the present study was to test the accuracy of Advanced Very High
      Resolution Radiometer (AVHRR) satellite derived temperature difference (dT) maps
      as a guide for the suitability of the environment for local snail hosts and
      Schistosoma development-transmission at the village level. The study provided
      field validation data from 13 villages in Kafr El Sheikh in the Nile Delta that
      sites present in wet zones of low dT value have more abundant snail populations
      than that present in the drier zones with high dT values. Results suggest that
      lower dT values were associated with wetter hydrologic regimes related to the
      level of underground water table and that this is reflected in the abundance of
      snail populations and Schistosoma snail infection rates at the village level.
      Water quality parameters on pH salinity and dissolved oxygen were not correlated
      with presence of Schistosoma infected snails. Results indicate that abundance of
      snails and S. mansoni prevalence are related to thermal-hydrology domains
      associated with surface water, that habitat suitability is related to depth to
      water table and that regional hydrology characteristics that affect snail host
      habitat suitability (ie. wet, moist, dry or very dry) can be evaluated using
      AVHRR dT maps.

PMID- 9257970
TI  - Susceptibility of three successive snail generations from positive and negative
      laboratory bred Biomphalaria alexandrina from different localities in Egypt to
      infection with Schistosoma mansoni from Giza.
AB  - Susceptibility of snail vectors to schistosome infection varies between
      geographical areas, populations in the same area and among individuals in the
      same population. It is also affected by biological factors of which are snail
      size (age), number and age of miracidia exposed to water, temperature,
      illumination and darkness. Our preview studies indicated that snails 4-6 mm in
      diameter exposed to 5 freshly hatched miracidia under light and in water at 25
      degrees C are optimum conditions for infection of Biomphalaria alexandria from
      various localities in Egypt with Schistosoma mansoni (TBRI strain maintained in
      hamsters). In the present study, groups of 16 snails from three successive
      generations from positive and negative laboratory bred B. alexandrina from Giza,
      Alexandria, Menoufia, Cairo and Minia were exposed to S. mansoni miracidia (TBRI
      Strain) from Giza under the above mentioned optimum conditions. From the 20th day
      infection snails were checked from cercariae shedding to estimate the prepatent
      period and their number from each snail light for one hour. B. alexandrina from
      the various localities in Egypt were susceptible to S. mansoni (TBRI strain)
      infection. Snails from Alexandria were the most susceptible, followed by those
      from Cairo, Giza, Menoufia and Minia. Snails from positive generations were more
      susceptible to infection than those from negative ones. However, there has been a
      decline in the susceptibility of snails from one generation to the next. The
      prepatent period for shedding of cercariae was 27 days in case of snails from
      positive generations and it was extended to 38 days among snails from negative
      ones. It can be concluded that: (1) There are different levels of susceptibility
      between B. alexandrina from the various localities in Egypt and infection with S.
      mansoni from Giza. (2) Unsusceptibility (refractory character) of B. alexandrina
      to S. mansoni infection could be a heritable character like susceptibility.
      Consequently, it would be beneficial to select actively resistant snails and mass
      culture them to increase the proportion of alleles for insusceptibility as a
      possible mean for biological control of schistosomiasis in natural population.

PMID- 9257971
TI  - Effect of ivermectin on experimental trichinosis.
AB  - Ivermectin is a potent macrolytic lactone causing paralysis in many nematodes and
      arthropods through an influx of chloride ions across cell membranes. This work
      was carried out to assess its effect against T. spiralis infection in Swiss
      albino mice as a single dose treatment. Ivermectin was administered to infected
      mice: one day before, the same day, 5, 10 and 35 days post Trichinella infection.
      Assessment of the drug effect was through: a) Parasitological study which
      included: adult count, Larval count, measurements of the length of the adult
      females, larvae and the reproductive capacity index; b) Scanning electron
      microscopic study of the adult & larva. Scanning EM changes were described, the
      results showed that it was most effective when administered on the same day of
      infection, its effect diminished progressively thereafter.

PMID- 9257972
TI  - A rapid diagnostic test for Trichomonas vaginalis infection.
AB  - The applicability of the quantitative buffy coat tube test (QBC) for diagnosis of
      T. vaginalis was studied. The results of the QBC tube test was compared with that
      of the wet mount examination in 60 women having genital infection. The cases were
      selected from outpatient clinic of El-Shatby University Hospital T. vaginalis was
      identified by QBC tube test in 24 cases out of 60 while the wet mount smear, it
      was detected in 21 cases. The sensitivity of the QBC tube test was 100% and the
      specificity was 92.3%. It was found that the QBC tube test seems to have a place
      in the routine diagnosis of T. vaginalis.

PMID- 9257973
TI  - Characterization of Leishmania aethiopica from rock hyrax, Procavia capensis
      trapped in Najran, Saudi Arabia.
AB  - Cutaneous leishmaniasis caused by L. aethiopica is endemic in Ethiopia, Kenya and
      South-west Africa. In a previous paper, the present authors reported natural
      Leishmania species infection in two hyraxes, P. capensis. In this paper, an
      isolate from a rock hyrax. P. capensis (Pallas, 1766) was enzymatically
      characterized by demonstrating the mobilities of seven enzymes, to be identical
      with the reference strain of L. aethiopica.

PMID- 9257975
TI  - Detection of circulating antigens in blood to evaluate treatment of fascioliasis.
AB  - This work was designed to assess cure of human fascioliasis after triclabendazole
      treatment by detection of Fasciola antigen by a modified double antibody sandwich
      ELISA technique. The results showed that the test detected the antigen in the
      sera of all studied cases before treatment, while no antigen was detected after
      treatment. The results may suggest that antigen detection provides an accurate
      tool for diagnosis as well as the assessment of cure.

PMID- 9257974
TI  - Filariasis transmission potential of mosquitoes to humans of different age
      groups.
AB  - Age-specific levels of Wuchereria bancrofti infection determined by
      microfilaremia in filarious 10 to 60 years old males from endemic village
      revealed that microfilaria intensity was higher in younger age, presumably
      because of increased vector biting rate of younger individuals. Out of 1334 Cx.
      pipiens captured while attempting to bite 51 child-adult bait pairs, 54.0%
      selected a host in the 10-15 age group. Biting preference towards children was
      more evaluated (79.2%) later than earlier in the night. Frequency distribution of
      age-specific biting collections indicated that 62.7% recorded exceeding numbers
      of bites on children, 21.6% adult biting, and 15.7% equal biting of one of the
      baits in the pair. Furthermore, 21.6% of the children were exposed to nightly
      bites ranging from 21 to 64 and only 7.8% of the adults experienced from 21 to 85
      bites. Mosquito biting intensity averaged 14.2 and 11.6 bites/night for children
      and adults respectively. Children experienced 22.4% more bites per night than
      adults. Thus, children are more exposed to filaria infection and seem to
      represent an important source of infection. It is concluded that attempts at
      widespread control of filariasis in the densely populated Nile Delta, where
      youngsters may account for an immense proportion of the local population, should
      concentrate on immatures.

PMID- 9257976
TI  - Visceral leishmaniasis with special reference to Egypt (review and comment).
AB  - The leishmaniases comprise several diseases of wide diversity of manifestations
      caused by different species of the genus Leishmania. They are grouped under three
      main headings: Cutaneous leishmaniasis, visceral leishmaniasis and mucocutaneous
      leishmaniasis. Leishmania donovani complex which visceralize in man with a
      predilection for infecting cells in the viscera, particularly in the spleen and
      the main vectors are Phlebotomus of the "major" group. These include L.d.
      donovani (Asia, mainly India and China), Ld. infantum (Mediterranean countries)
      infects mainly children and L.d. chagasi (South America) infects adults and
      children. In this paper, the historical background of L. donovani and L. infantum
      with special reference to Egypt is given. Not all the previous references were
      included, but many of them were cited. Comment was given whenever indicated.

PMID- 9257977
TI  - Comparative effect of tiaprofenic acid and piroxicam alone and as adjuvants to
      praziquantel in Schistosoma mansoni infected mice.
AB  - Non steroidal anti-inflammatory drugs (NSAIDs) (tiaprofenic acid and piroxicam
      have been used alone and as adjuvants to praziquantel in treating hepatic
      granuloma in Schistosoma mansoni infected mice. Granuloma diameter, histamine
      metabolism, cyclic AMP and PGE2 levels have been measured at the end of
      treatment. Tiaprofenic acid effectively reduced the size of hepatic granuloma,
      significantly increased histamine forming capacity, CAMP level and significantly
      decreased plasma PGE2 level. Piroxicam had no significant effect on granuloma
      size, significantly decreased histamine forming capacity, CAMP and PGE2 levels.
      The combined therapy of either of the drugs with praziquantel did not result in
      an additive effect.

PMID- 9257978
TI  - Endoscopic control of gastric variceal bleeding with butyl cyanoacrylate in
      patients with schistosomiasis.
AB  - This trial represents the Egyptian experience in cyanoacrylate injection for
      hemostasis of bleeding gastric varices. One hundred patients with portal
      hypertension due to schistosomal hepatic fibrosis and/or posthepatitic liver
      cirrhosis were included. All patients presented with bleeding from gastric
      varices either fundal (80 patients) or inferior extension of esophageal varices
      (20 patients) were enrolled. Injection therapy was administered as the first
      active measure. No tamponade or drugs were used. Cyanoacrylate was mixed with
      lipid and injected through a hand-made probe. A mean of 3 (range 1-9) ampoules of
      cyanoacrylate were used per injection session. Bleeding stopped at the end of all
      sessions. Ten patients (12.5%) with fundal varices had rebleeding during the
      first 24 hours. Reinjection could control bleeding in 6 patients with a total
      success rate of 95%. Four patients were managed surgically. Fatal pulmonary
      embolism developed in one patient (1.25%) with fundal varix. Five more patients
      (6.25%) died from bleeding-related liver failure. In conclusion, injection of
      cyanoacrylate is highly satisfactory in controlling bleeding from both types of
      gastric varices.

PMID- 9257979
TI  - Studies on granuloma formation in Syrian hamsters experimentally infected with
      Schistosoma mansoni.
AB  - The formation of granuloma in Syrian hamsters was studied. The granulomatous
      reaction started with accumulation of T-cells which subsequently attract the
      eosinophils by their products, then aggregation of eosinophils and neutrophils
      around the living egg(s) to destroy egg shell. Consequently, the eosinophils
      immediately attack the miracidium and release their cytotoxic products to
      dissolve it. Later on, the macrophages accumulate, in cooperation with
      eosinophils, release their fibrogenic factors, stimulate the formation of
      granulomatous tissue and ultimately fibrosis takes place. The dissolving of both
      egg shell and miracidium by eosinophilic products proves their ability to deal
      with both egg shell (hard part) and the miracidium itself (soft part) and this
      confirms their great ability to play a main role in the immunity against
      helminthic infection. The different morphological variations of the granuloma are
      included and the role of other inflammatory cells is also discussed.

PMID- 9257980
TI  - Changes in serum lipids of mice experimentally infected with Schistosoma mansoni.
AB  - Serum samples of mice infected with 80 cercariae of Schistosoma mansoni for
      different time periods (2-20 weeks) were used in this study. It was observed that
      the concentrations of serum total cholesterol and triacylglycerol decreased
      significantly (P < 0.001, P < 0.0001 respectively) in infected as compared to
      control mice starting from the fourth week post infection. Similarly, the
      concentration of serum high density lipoprotein-cholesterol (HDL-C) decreased
      significantly (P > 0.001) in infected as compared to control mice. However, the
      serum lipoproteins profile was variable at different stages of infection. On the
      other hand, the liver weight increased significantly (P < 0.0001) in infected as
      compared to control mice starting from the sixth week post infection. These
      changes might be attributed to several metabolites released by S. mansoni which
      affect the host hepatic tissue resulting in decreased synthesis of these
      parameters and their release into the circulation.

PMID- 9257981
TI  - Distribution and abundance of house dust mites, Dermatophagoides spp., in
      different ecological localities in Esna City, Kena Governorate, Egypt.
AB  - The distribution and abundance of house dust mites, Dermatophagoides spp. were
      studied in July, September and November, 1995 in three different localities in
      Esna City, Kena Governorate, Upper Egypt. During these months, 15 houses were
      sampled in each locality. 87% of riverside houses were infested with mites where
      D. pteronyssinus dominated (80%) over D. farinae. Sixty percent of the valley
      houses sampled were infested, where D. farinae was dominant (66%). Densities of
      both Dermatophagoides spp., were considerably higher in riverside than in valley
      houses. Live mites were not found in the lightly infested houses sampled in the
      desert area (54% positive). Relative humidity, which varied in houses located in
      different climatic localities in Esna City, was noted to be the principal
      limiting factor influencing the distribution and abundance of both species.
      Temperature did not appear to be an important factor influencing the distribution
      and abundance.

PMID- 9257982
TI  - Toxoplasmosis in last four years in Agean region, Turkey.
AB  - Anti-Toxoplasma antibodies were determined with IFA and ELISA tests in 9410
      patients who were different age groups, attended Department of Parasitology
      between 1991-1995. Anti-Toxoplasma IgG antibodies were found positive in 4651
      (49.4%) of these patients. 2287 (21.4%) patients were pregnant women and the
      positivity was 55% of them. According to history of these patients,
      seropositivity was found 50% in women having spontaneous abortion, 52% in women
      having stillbirth, in 55% women having abnormal fetal births. These patients and
      their culinary habits, the presence of cats and relationship with other clinical
      symptoms were also evaluated.

PMID- 9257983
TI  - Serum erythrocyte and leukocyte adenosine deaminase activities in patients with
      vivax malaria in Turkey.
AB  - Adenosine deaminase (ADA) activities in serum samples, erythrocytes, leukocytes
      and plasma hemoglobin concentrations were investigated in 50 patients with vivax
      malaria and compared with control group. ADA activity was determined by Bertholet
      reaction. Student's t-test and correlation analyses methods were used for
      statistical analyses. Serum ADA activity in patients with vivax malaria 49.20 +/-
      29.02 IU/I, in control 21.15 +/- 8.04 IU/I (p = 0.005), erythrocyte ADA activity
      in patients 2.91 +/- 1.23 U/gr Hb, in control 1.65 +/- 0.59 U/gr (p = 0.001),
      leukocyte specific ADA activity in patients 26.23 +/- 20.21 U/mg protein, in
      control 25.84 +/- 9.19 U/gr Hb were determined (P > 0.05). Plasma hemoglobin
      concentration in patients 29.25 +/- 28.10 ml/dl, in control 9.80 +/- 13.14 mg/dl
      were also determined. There is no significant correlation among mentioned
      parameters. Erythrocyte purine salvage pathway is accelerated by Plasmodium to
      provide preformed purine source which can not be synthesized by Plasmodium to
      provide preformed purine source which can correlation between plasma hemoglobin
      concentration and serum ADA activity suggests that increased serum ADA activity
      may develop secondarily to the disease independently from the hemolyses. No
      higher ADA activity level than expected value of leukocytes may reflect
      immunosuppression of leukocytes.

PMID- 9257984
TI  - Alpha feto-protein and albumin in ascitic fluid in hepatocellular carcinoma
      patients.
AB  - Alpha-feto-protein (AFP) is the most popular tumor marker for hepatocellular
      carcinoma (HCC). It is used in diagnosis and follow up of cases by estimating its
      rise in the serum. The aim of this work is to study the value of estimating AFP
      in ascitic fluid of HCC patients with ascites. This work is a case control study
      on 32 patients, including 22 cases with ascites and HCC and 10 control group with
      ascites due to liver cirrhosis without HCC. The level of AFP was estimated in
      serum and in ascitic fluid by Radio-immuno assay RIA. The serum ascites albumin
      gradient (SAAG) was assessed by measuring albumin in all samples using
      bromocresole green dye binding. Guided aspiration liver biopsy and ascitic fluid
      cytology was done, stained with H & E. It was found that, AFP level in serum was
      elevated in 72.7% of HCC patients, and in ascitic fluid was elevated 63.6% HCC
      patients. Also, there was a highly significant, direct positive correlation
      between elevation of AFP in serum and in ascitic fluid (r = 0.778). No elevation
      of AFP in serum and in ascitic fluid was detected in control group. Ascitic fluid
      cytology showed malignant cells in one case only. SAAG was significantly lower in
      the HCC group 0.83 gm/dl than the control group 2.43 gm/dl (p-value < 0.001).
      Elevation of AFP in ascitic fluid is of high importance in evaluation of HCC, and
      is as significant as serum and runs parallel to it. Estimation of AFP in ascitic
      fluid is much more significant in evaluation of HCC cases than ascitic fluid
      cytology.

PMID- 9257985
TI  - Eimeria schmidti n. sp. (Apicomplexa: Eimeriidae) from the sandy fringe-toed
      lizard (Acanthodactylus schmidti) in Saudi Arabia.
AB  - Eimeria schmidti n.sp. is described from the gall bladder of Acanthodactylus
      schmidti from Al-Thomama area in the central region of Saudi Arabia. Sporulated
      oocysts are ellipsoid 31.2 x 23.3 (26.9-36.4 x 21.2-26.0). Oocyst wall is smooth,
      greenish yellow, 1.31 (1.16-1.41) um thick and two-layered. Micropyle, polar
      granule and oocyst residuum are absent. Sporocysts are ellipsoid 12.6 x 9.3 (10.9
      14.1 x 7.6-10.0) um. Sporocyst residuum is present. The sporocysts lack a stieda
      body. Sporozoites are banana shaped blunt at one end and tapered at the second
      end. Eimeria species from Lacertidae are compared.

PMID- 9257986
TI  - Intestinal parasites among food-handlers in Qualyobia Governorate, with reference
      to the pathogenic parasite blastocystis hominis.
AB  - A total of 1700 male food handlers, above 20 years of age who came for health
      clearance certificate were the subjects of the present study. Health assessment
      questionnaire was filled out on each person including dietary habits, water
      supply, history of diarrhoeal disease. Clinical examination and stool samples
      collection in 3 alternative days were performed. The food handlers were divided
      into symptomatic (700) and saymptomatic (1000). Different concentration methods
      as well as test tube culture for Strongyloides larvae were done. Samples were
      preserved in PVA, trichrome stained slides were examined for protozoal parasites.
      Nineteen percent had intestinal parasites, G. lamblia, E. histolytica, A..
      lumbricoides, S. mansoni, A. duodenale, T. trichura, H. nana, St. stercoralis, E.
      vermicularis and mixed infection & non-pathogenic; E. coli, I. Butschlii, C.
      mesnilli, E. nana, T. hominis and mixed infection. Blastocystis hominis was
      recovered from stools of 8.5% of symptomatic and 4% of asymptomatic. 2.4%
      symptomatic and 2% asymptomatic had B. hominis significant infection. B hominis
      was considered significant if > 5 organisms per HPF was counted. Significant
      infection was higher among symptomatic than asymptomatic persons with detectable
      faecal leucocytes especially eosinophils. The authors recommended that physicians
      as well as diagnostic parasitologists should be aware of the potential clinical
      significance of B. hominis especially, when present alone in significant number,
      otherwise positive cases must be considered as carriers and followed up for any
      ill effects.

PMID- 9257988
TI  - Oestrus ovis (sheep nasal fly) infesting the eyes and the nose of a camel keeper
      family.
AB  - Myiasis is a medical and veterinary health problem in many animal rearing
      countries. It is not a new problem in Egypt. A family of five persons were
      infested in the eyes (5) and nose (2) with the larvae of Oestrus ovis. It is
      concluded that the physicians in the MOH rural health units should keep in mind
      opthalmomyiasis when dealing with non specific catarrhal conjunctivitis
      particularly those people who are concerned with rearing of farm animals.

PMID- 9257987
TI  - Identification of surface tegumental antigens of normal and irradiated
      schistosomula.
AB  - Sodium dodecyl sulphate- poly acrylamide gel electronphoresis (SDS-PAGE)
      fractionation of tegumental surface antigens (STEG-Ags.) of 7-day cultured normal
      and irradiated schistosomula showed no obvious qualitative differences. The
      observed polypeptide bands of both normal irradiated STEG-Ags. were almost
      identical and have similar corresponding molecular weights. The immunoblotting
      assay, using different types of mouse sera, revealed similarity between the bands
      of both normal and irradiated STEG-Ags. recognized by each type of mouse serum.
      No qualitative rather than quantitative differences have been observed. The
      quantitative differences were reflected in intensively staining of some bands
      from normal STEG-Ag. rather than their corresponding bands of the same molecular
      weights from irradiated STEG-Ag.

PMID- 9257989
TI  - Immunological pattern in Syrian golden hamsters experimentally infected with
      Schistosoma mansoni and Leishmania d. infantum.
AB  - The immunoglobulins (IgG, IgM, IgE, & IgA) and the complements (C3 & C4) were
      studied in hamsters as result of a single infection (S. mansoni or L.d. infantum)
      and as concomitant infection (L.d. infantum on top of S. mansoni). The
      immunological pattern showed profound IgG and IgA increase in the concomitant
      group than either infection alone. Also, concomitant infection induced more IgE
      increase than either infection alone. On the other hand, C3 and C4 showed more
      decrease in concomitant infection. The whole results were discussed.

PMID- 9257990
TI  - Insecticidal activity of Calotropis procera extracts of the flesh fly, Sarcophaga
      haemorrhoidalis fallen.
AB  - The insecticidal activity, expressed by LD50 values, of acetone, ethanol,
      petroleum ether and water extracts of Calotropis procera leaves against the flesh
      fly, Sarcophaga haemorrhoidalis Fallen was evaluated in the laboratory. Based on
      LD50 values, ethanol extract was nearly 1.7, 1.3 and 1.3 times more toxic to
      larvae than water, petroleum ether and acetone extracts, respectively. It was
      1.9, 1.4 and 1.2 times more toxic to pupae than water, acetone and petroleum
      ether extracts, respectively. It was 2.0, 1.5 and 1.4 times more toxic to male
      flies and 2.2, 1.6 and 1.4 times more toxic to female flies than water, petroleum
      ether and acetone, extracts, respectively. Thus, ethanol extract of C. procera
      was the most toxic, of all solvents used, to different stages of S.
      haemorrhoidalis. Findings suggest also that C. procera extracts may produce
      larvicidal, pupicidal and adulticidal effects, (behaving like general toxicants)
      against the flesh fly, S. haemorrhoidalis.

PMID- 9257991
TI  - Free living amoebae as opportunistic parasites in immunocompromised hosts.
AB  - The acquisition of invasiveness of mammalian tissue by free living amoebae (FLA)
      is an extremely noteworthy phenomenon. Many factors may be responsible for this
      evolutionary change in their physiology. The present work aimed to clarify the
      host factors in this problem. Albino mice were the laboratory animals used in
      this work. Non-pathogenic strains of FLA were isolated from ear, nose and
      pharyngeal swabs and from contact lenses of patients attending out patient
      clinics in Benha University Hospitals. Isolation was done by cultivation of non
      nutrient agar at 37 & 43 degrees C and identification was made by flagellation
      test. The degree of pathogenicity of isolated strains was assessed by using
      animal pathogenicity test. Endoxan (0.7 mg/kg) and Prednisolone (2 mg/kg) were
      used for 15 days orally to suppress the immunity of clean mice before their
      inoculation intranasally with the isolated strains. All groups were observed for
      3 weeks post-infection. Mortality rates recorded were higher in Endoxan or
      Prednisolone treated and Naegleria infected groups A I & B I (20 & 15%
      respectively) than Endoxan or Prednisolone treated and acanthamoeba infected
      groups A II & B II (10%) and drug control (10%). Histopathological examination of
      brain and meninges revealed severe changes in form of severe meningoencephalitis,
      severe vacuolar degeneration, and moderate haemorrhage and necrosis in brains of
      groups AI & BI and less severe changes in groups AII & BII (10%) form of-non
      granulomatous encephalitis. Drug control groups showed negligible changes. Great
      attention must be paid to reveal the presence of FLA before using
      immunosuppressive drugs in human cases.

PMID- 9257992
TI  - Seven outbreaks of trichinosis in China (1992-1996).
AB  - Seven outbreaks of trichinosis occurred in Zhengzhou (central China) from 1992 to
      1996, 250 patients were diagnosed. Trichinella larvae were found in 3 of 4
      portions of the pork examined and in 5 of 7 cases by muscle biopsy. There was a
      higher occurrence of outbreaks in winter. Young and middle-aged workers, cadres
      and merchants were the majority of patients, (higher in males than in females).
      The most important clinical manifestations were fever, eyelid edema, tiredness
      and eosinophilia without any gastrointestinal symptoms, rash and with less
      myalgia. Anti-Trichinella antibodies were detected by IF in 62.6% individuals
      with the history of infection. The specific antibodies were only observed in 78%
      patients one week after onset of disease, while the antibody positive rate was
      increased to 92.5%, 97.6% and 100% two, three, four and five weeks after the
      onset and evidently increased from 89.6% before therapy to 100% one week after
      therapy, and decreased to 74.6% and 23.7% one and four months after therapy
      respectively, which suggested that IF was a useful tool for immunodiagnosis and
      checking up therapeutic effect of trichinosis.

PMID- 9257993
TI  - Ultrastructure study of experimental cutaneous leishmaniasis before and after
      Dapsone intake.
AB  - Leishmania strain was isolated from a human case of cutaneous leishmaniasis and
      inoculated into experimental animals. Group of infected animals were given
      Dapsone, at a dose of 25 mg/kg for 3 weeks. Results showed that infected animals
      suffered from autoamputation of the inoculated foot pad. On the other hand, those
      receiving Dapsone showed complete clinical cure. Transmission Electron Microscope
      of both groups revealed the fine structure of Leishmania amastigotes. Those given
      Dapsone showed considerable reversible changes which didn't affect parasitic
      virulence. This latter has been demonstrated by their ability to infect
      experimental animals. leading to pathological lesion. It should be pointed out
      that patients treated with this drug and showed marked clinical response must be
      very carefully examined for fear of residual parasites which may be the cause of
      relapse later on.

PMID- 9257994
TI  - Confirmation of clinical differentiation of three Leishmania strains by
      computerized image analyser system.
AB  - Three human strains of Leishmania, one visceral and two cutaneous leishmaniasis
      were prepared from both culture and tissue of infected animals and subjected to
      analysis by computerised image analyser system. The results showed differences in
      the morphology and nucleic acid contents of the three strains.

PMID- 9257995
TI  - Helicobacter pylori among Egyptian patients with chronic liver diseases. A
      comparative study.
AB  - The prevalence of Helicobacter pylori in Egyptian patients with different stages
      of liver diseases was compared to those with normal liver status. Eighty patients
      subjected to upper gastrointestinal endoscopy were enrolled. They were divided
      according to their liver status into two groups; the first patients with liver
      cirrhosis and the second who had no liver affection. Gall bladder diseases were
      excluded by abdominal ultrasound examinations. Endoscopic antral mucosal biopsies
      were used for H. pylori screening by both culture and urease test, and for
      histopathological examinations. Both groups were matched as regards age, sex, and
      socioeconomic conditions. Culture was positive in 42.2% and 40.7% of patients in
      both groups respectively (P > 0.05). Urease test showed positive results in 58%
      and 76.6% in both groups respectively (P > 0.05). Helicobacter pylori prevalence
      showed no significant differences between both studied groups as regards age,
      sex, or type of gastric lesions. Furthermore, liver status in patients with
      chronic liver diseases does not play a role in distribution of infection. The
      study shows the high prevalence of H. pylori among Egyptians and the absence of a
      relation between H. pylori and chronic liver diseases.

PMID- 9257996
TI  - An evaluation of the modified agar plate method for diagnosis of Strongyloides
      stercoralis.
AB  - An examination of 320 random stool samples from patients aged 7-60 years in Kafr
      Sakr Hospital, was done to compare the efficacy of modified agar plate method to
      traditional method for diagnosis of Strongyloides stercoralis infection. Out of
      320 cases examined 27 were positive for strongyloidiasis by all means. The
      traditional methods detected 37% and 48.1% from the positive cases by single and
      repeated 3 days examination respectively. The modified agar plate detected 70.3%
      and 96.2% among positive cases by single and 3 days examination respectively. The
      modified agar plate was twice efficient than the traditional methods. Precautions
      taken to obtain the best result were discussed. Considering the other advantages
      of this technique, it was concluded that it may eventually become the test of
      choice in diagnosis of strongyloidiasis.

PMID- 9257997
TI  - The effect of Schistosoma mansoni infection on testicular lipid in mice.
AB  - This study was performed to establish the changes in the level of some serum
      hormones (Follicle stimulating hormone "FSH", Leutinizing hormone "LH" and
      testosterone) as well as to determine the changes in the concentrations of some
      testicular lipid parameters (viz., total cholesterol and total triacylglycerols)
      of infected mice with Schistosoma mansoni for different periods of time. Electron
      microscopical studies were also performed to define any histological changes in
      the testis upon infection with S. mansoni. The serum levels of gonadotropins
      (FSH, LH) showed no significant changes in infected as compared to control mice.
      On the other hand, the serum level of testosterone showed a significant decrease
      (P < 0.001) in infected as compared to control mice starting form the 14th week
      post infection. Testicular lipids showed a significant increase (P < 0.01) in the
      concentration of total cholesterol and a significant decrease (P < 0.005) in the
      concentration of total triacylglycerols in infected as compared to control mice
      especially at late stages on infection (14-20 weeks post infection). However,
      electron microscopical studies showed non significant histological changes in the
      testicular tissues of infected mice at different stages of infection. It is
      concluded that schistosomiasis has an important metabolic effect on testicular
      lipids as well as on the serum level of testosterone, whereas structural changes
      and spermatogenesis might require a longer period of infection and/or severe
      infection with higher number of cercariae.

PMID- 9257998
TI  - The effects of host population density on the epidemiology of the trichostrongyle
      nematode Heligmosomoides polygyrus.
AB  - The present study considers the effect mouse population density on the fecundity,
      expressed as daily egg output per gram of faeces, and infectivity of the
      trichostrongyle nematode. Heligmosomoides polygyrus and in the field mouse
      (Apodemus sylvaticus) and H. p. bakeri in laboratory mouse (CD1). The higher host
      density resulted in an increased fecundity of H. polygyrus compared with medium
      and lower host densities. However, the number of H. p. polygyrus and H. p. bakeri
      recovered 30 days post-infection indicated an increase in worm recovery with
      increasing host population density. Overcrowding in a host density may affect
      susceptibility to infection as a result of stress-mediated immunodepression.

PMID- 9257999
TI  - Pairing of Schistosoma mansoni males in infected Syrian hamsters.
AB  - Pairing of male schistosomes in the liver of infected hamsters was recorded with
      Egyptians S. mansoni strain. The homospecific male pairs never carried each other
      in the gynaecophoric duct, but they being closed in either central or hepatic
      veins. Other perfused males and females en copula showed normal mating behaviour.
      The paired males were more or less in the same size. The random sexed miracidia
      used resulted in obtaining 1:2.1 female/male ratio. It is concluded that the
      random increase of male schistosomes may create the male pairing behaviour. Also,
      the migration of female against the blood stream to the mesenteric plexus of the
      host and the failure of male to catch them may lead to this homosexual pairing.
      The black haemozoin-like substance seen in mature females was also observed in
      the pairing males and this probably reflects the effect of scarcity or migration
      of females to the mesenteric plexus.

PMID- 9258000
TI  - Comparative studies on the effect of bithionol, praziquantel and triclabendazole
      in rabbit's fascioliasis.

PMID- 9258001
TI  - Another look at parastichies.
AB  - Parastichies, the patterns of curves seen on the flowering heads (capitula) of
      sunflowers and other members of the Asteraceae family, is of continuing interest
      to botanists and mathematicians alike. The purpose of this article is to show how
      the visibility of parastichies depends on the spacing of the florets on the
      capitula. In particular, it is shown that a parastichy is not visible where the
      florets are most closely spaced and that, for parabolic curves, opposed
      parastichy pairs intersect perpendicularly near their points of minimum spacing.

PMID- 9258002
TI  - The effect of time delays on the dynamics of avascular tumor growth.
AB  - During avascular tumor growth, the balance between cell proliferation and cell
      loss determines whether the colony expands or regresses. Mathematical models
      describing avascular tumor growth distinguish between necrosis and apoptosis as
      distinct cell loss mechanisms: necrosis occurs when the nutrient level is
      insufficient to sustain the cell population, whereas apoptosis can occur in a
      nutrient-rich environment and usually occurs when the cell exceeds its natural
      lifespan. Experiments suggest that changes in the proliferation rate can trigger
      changes in apoptotic cell loss and that these changes do not occur
      instantaneously: they are mediated by growth factors expressed by the tumor
      cells. In this paper, we consider two ways of modifying the standard model of
      avascular tumor growth by incorporating into the net proliferation rate a time
      delayed factor. In the first case, the delay represents the time taken for cells
      to undergo mitosis. In the second case, the delay represents the time for changes
      in the proliferation to stimulate compensatory changes in apoptotic cell loss.
      Numerical and asymptotic techniques are used to show how a tumor's growth
      dynamics are affected by including such delay terms. In the first case, the size
      of the delay does not affect the limiting behavior of the tumor: it simply
      modifies the details of its evolution. In the second case, the delay can alter
      the tumor's evolution dramatically. In certain cases, if the delay exceeds a
      critical value, defined in terms of the system parameters, then the underlying
      radially symmetric steady state is unstable with respect to time-dependent
      perturbations. (For smaller delays, this steady state is stable). Using the delay
      as a measure of the speed with which a tumor adapts to changes in its structure,
      we infer that, for the second case, a highly responsive tumor (small delay) has a
      better chance of surviving than does a less-responsive tumor (large delay). We
      also conclude that the tumor's evolution depends crucially on the manner and
      speed with which it adapts to changes in its surroundings and composition.

PMID- 9258003
TI  - The inverse problem of electrocardiography: a solution in terms of single- and
      double-layer sources of the epicardial surface.
AB  - An approach to the inverse problem of electrocardiography that involves an
      estimation of the electric potentials (double-layer equivalent sources) on the
      heart's epicardial surface from the electrocardiographic potentials that are
      measurable on the body surface has received considerable attention. This report
      deals with a heretofore unexplored extension of this approach, one that yields,
      in addition to the electric potentials on the epicardial surface, the normal
      components of their gradients (single-layer equivalent sources). We show that
      this formulation has at least three advantages over the formulation in term of
      epicardial potentials alone: (1) single-layer equivalent sources, which reflect
      the flow of current across the epicardial surface, are well suited for the
      imaging of regional ischemia and infarction; (2) the transfer matrix linking the
      epicardial and body-surface potentials for this formulation is less ill
      conditioned than that for the formulation in terms of potentials alone; (3) the
      input vector for inverse calculations consists of spatially filtered (rather that
      directly measured and therefore noise) body-surface potentials. To establish the
      feasibility of this new formulation of the inverse problem and to compare it with
      the formulation in terms of potentials alone, we used a realistically shaped
      boundary-element model of human torso. By calculating singular values less ill
      conditioned. We then directly calculated epicardial and body-surface potentials
      for a single dipole located centrally and for three simultaneously active dipoles
      located eccentrically in the torso's heart region and used these results to test
      three methods that are prerequisites of a successful inverse solution: Tikhonov
      regularization, linearly constrained least squares, and an L-curve method. The
      feasibility of the new formulation was demonstrated by the fact that the method
      based on the linearly constrained least squares improved on overregularized
      Tikhonov solutions over a wide range of regularization parameters, and it yielded
      solutions that were more accurate than the best-possible Tikhonov solutions.
      Moreover, the L-curve solution procedure, which requires no a priori information
      about the solution, yielded slightly underregularized, but accurate, estimates
      for the optimal regularization parameter and the corresponding best-possible
      Tikhonov solution. Our results also showed that replacing--in the interest
      computational economy--quadrature formulas for the planar triangles with various
      approximate formulas for the nodes of the model reduces the accuracy of the
      inverse solution.

PMID- 9258004
TI  - Prey dominance in discrete predator-prey systems with a prey refuge.
AB  - The effects of a prey refuge in a multiprey discrete system with predation is
      studied. We demonstrate the stable coexistence of species that would otherwise
      exclude each other without a prey refuge. With a prey refuge, we show that an
      endangered prey not only recovers from the brink of extinction, but also
      dominates the system. We invent notions of dominance that guarantee the
      extinction of all the dominated prey in the system. With the extermination of
      most of its prey, the predator either coexists with the dominant prey or is
      driven to extinction. By using a precise mathematical definition, we obtain that
      a prey with a sufficiently high carrying capacity persists in a predator-prey
      system with a prey refuge.

PMID- 9258005
TI  - Asbestos bodies in bronchoalveolar lavage fluid and sputum.
AB  - The aim of the study was to determine the concordance of asbestos body (AB)
      detection in sputum and bronchoalveolar lavage fluid (BALF). AB were detected in
      the BALF of 110 former or current asbestos workers with medium weak exposure
      level and, for 65 subjects, in sputum. Several spontaneous sputum samples were
      taken from each subject. AB prevalence in BALF was rather low (48.2%) especially
      in subjects with former chrysotile exposure (32.5%). AB prevalence was lower in
      smokers (40.9%) and ex-smokers (40.7%) than in non-smokers (68.7%). In the sub
      group, who underwent both sputum and BALF examination, the concordance of AB
      detection was observed only in 56.8% of the cases. Neither of the two methods had
      significant prevalence over the other but were complementary, as both are useful
      in increasing the probability of AB detection.

PMID- 9258006
TI  - [Advances in studies on the release and modulation of fever].

PMID- 9258007
TI  - [Sepsis--generalized infection. The treatment of adults based on personal
      observations].
AB  - Basing on the own experience, the authors discuss causative treatment of sepsis,
      mainly of unknown etiology. Emphasis is on the depression of immunological system
      in the acute phase of the disease. Therefore, a combined treatment with 2, often
      3 or even 4 bacterial antibiotics is recommended, together with passive
      immunotherapy, and in certain cases surgical removal of the infection foci.

PMID- 9258008
TI  - [Sepsis--a generalized infection. Etiopathogenetic, diagnostic and clinical
      problems in adults based on personal experiences].
AB  - Etiopathogenetic, diagnostic, and clinical problems seen in the adult patients
      with sepsis have been discussed. An emphasis is on the diagnostic problems in an
      early stage of infection as well as bacteriological findings. The authors stress
      that sepsis usually develops in patients with depressed immunological system.

PMID- 9258010
TI  - Health care professionals focus on prevention of medication errors. American
      Society of Consultant Pharmacists.

PMID- 9258009
TI  - Gamma knife: the treatment that saved my husband's life.

PMID- 9258011
TI  - Chronic cancer pain. National Cancer Pain Coalition.

PMID- 9258012
TI  - Recertification in pharmacology: NAPNES certified LP/VNs affected.

PMID- 9258013
TI  - Skin diseases lower self perception, study finds.

PMID- 9258014
TI  - Nursing care of the client with AIDS.
AB  - The client who has an immune deficiency manifests clinical symptoms that vary in
      severity and occur in multiple systems of the body. However what is known at the
      present time for the client with HIV infection is that the development of AIDS
      may occur from 18 months to more than 10 years after the initial infection. At
      the present time, AIDS is not curable; and is a disease that progressively
      worsens and ends in death from one or more of the complicating illnesses.
      Supportive care by the nurse is essential to assist the client to maintain
      maximum quality of life and a sense of self-esteem and self-efficacy. Since
      personal factors influence how rapidly a person's HIV-positive status progresses
      to AIDS, reducing re-exposure to HIV, optimizing nutritional status, avoiding
      pregnancy and stress are factors that the client should consider in optimizing
      quality of life.

PMID- 9258015
TI  - Smoking and hypertension.

PMID- 9258016
TI  - Role of nursing personnel in implementing clinical pathways and decreasing
      hospital costs for major vascular surgery.
AB  - Collaboration with key nursing personnel is essential to successfully implement
      clinical pathways, establish a dedicated vascular wing, and achieve significant
      hospital cost savings while still maintaining quality care with low morbidity and
      mortality rates. Key nursing personnel met once a month during a 1-year period
      with vascular surgeons, hospital administrators, and health care advisors to plan
      strategies to develop clinical pathways and establish a dedicated vascular ward.
      The pathways were then implemented. We compared morbidity, mortality, readmission
      rates, adn hospital costs among two groups of patients admitted for major
      vascular surgery. Nursing personnel, attending staff, and surgical residents
      found that treating patients who had undergone major vascular surgery was more
      straightforward and efficient after clinical pathways and a dedicated vascular
      wing were established. In addition, there were no significant differences between
      the groups in terms of overall mortality or pulmonary, neurologic, or cardiac
      complications despite shorter hospital stay and decreased hospital costs. Also
      there were no significant differences in readmission rates within 30 days.

PMID- 9258017
TI  - Nursing management and follow-up of the postoperative vascular patient in a
      clinic setting.
AB  - Patient follow-up after vascular surgery in a clinic setting provides prompt
      evaluation of patients, opportunity for education, and comprehensive care through
      direct patient and family teaching. These services are provided by a lead clinic
      RN experienced in medical/surgical care and a certified RN first assistant, who
      has specialized training and proficiency in perioperative nursing practice.
      Patients and their families depend on nurses in perioperative and outpatient
      settings to provide expertise, support, and understanding during the recovery
      process. This article presents a collaborative model of intervention, management,
      and follow-up by nurses in these settings.

PMID- 9258018
TI  - Relationship of study participation to health-related behaviors.
AB  - This study explores the ways in which clinical trial participation influences a
      person's health and health-promoting behaviors. Active study subjects with a
      minimum of 4 months' clinical trial participation were mailed a nurse-developed
      questionnaire. Seventy-three percent of the targeted group returned the survey by
      the deadline. The majority of respondents made changes toward better health. Diet
      modification, initiation of an exercise program, and smoking cessation were the
      changes cited most frequently. The study team was found to be influential in
      promotion of health. The nurse, the pivotal member of the team, provided subjects
      with the most health-related information. Most respondents believed they had
      enough information to change behaviors detrimental to health.

PMID- 9258019
TI  - Decision making in prevention and treatment of arterial leg ulcers: use of patho
      flow diagramming.
AB  - Ulceration is a serious outcome of arterial occlusive disease. The nurse must
      learn when interventions are appropriate and under what conditions. One method
      that is useful for decision making by the advanced nurse or for teaching of
      decision making to the novice nurse is the use of patho-flow modeling. Patho-flow
      modeling was devised at the University of Texas-El Paso, for use in teaching
      students critical thinking and decision making. It adapts well to specific
      disease entities. This article elaborates on the model and provides an annotated
      model for use in the practice setting.

PMID- 9258020
TI  - Celiac band syndrome (median arcuate ligament syndrome).

PMID- 9258021
TI  - Surveillance of vascular incisions: outcomes a four-year unit-based quality
      improvement program.
AB  - In a health care climate that emphasizes improving patient outcomes as well as
      reducing costs of care, the quality improvement process can be an effective tool
      to identify changes in practice that affect both of these factors in positive
      directions. Nursing staff members on our vascular surgical ward recognized
      incisional healing as critical to both cost of care and outcome. Infections and
      non-healing vascular incisions were problems that resulted in lengthy
      hospitalizations, the use of expensive antibiotics, and many read missions.
      Beginning in fiscal year 1992, nurses began monitoring incisional healing in
      vascular patients as part of the unit-based quality-improvement program. For 3
      years nurses collected and analyzed data related to incisional healing in
      patients with postoperative groin, leg, and amputation incisions. They
      communicated with interdisciplinary colleagues about ways to improve outcomes and
      identified and implemented changes in practice that resulted in improvements. A
      formalized research program is underway to increase knowledge related to
      incisional healing and factor that affect healing in this specialty population.

PMID- 9258022
TI  - Marfan's syndrome: a family affair.
AB  - Marfan's syndrome (MFS), a heritable connective tissue disorder, may result in
      cardiac valvular insufficiency, aortic aneurysm or dissection, dislocated lens,
      and musculoskeletal abnormalities. During a 20-month period (1994-96), an
      interdisciplinary health care team at a central Virginia medical center evaluated
      the histories of 112 persons from 15 different families for the presence of MFS
      related traits. Seventy-five had at least one MFS-related trait, and 27 subjects
      underwent echocardiography to evaluate for aortic root dilatation and valvular
      lesions. Forty-three patients (57.3%) in the above cohort demonstrated
      significant cardiovascular lesions, with 20 undergoing cardiac surgery. Thirty
      one patients (41.3%) were initially seen with significant ocular lesions, and 38
      (50.7%) displayed orthopedic deformities. The health care team developed
      strategies for long-term management of persons with MFS, including
      antihypertensive therapy, periodic testing, risk-factor modification, genetic
      counseling, and surgery for appropriate patients. Proactive, consistent
      management of MFS families will improve long-term health outcomes for this
      patient population.

PMID- 9258023
TI  - The quality of life of the limb-threatened patient after lower-extremity
      revascularization.
AB  - There is limited research evaluating the quality of life after lower-extremity
      revascularization surgery. Nursing is concerned not only with survival and
      decreased morbidity, but also with the whole patient. An impact analysis survey
      was used to investigate whether patients perceived their quality of life to be
      improved after they underwent lower-extremity revascularization surgery. The
      Medical Outcomes Study-36 (MOS-36, 1990) survey was used to help us assess the
      patients' overall perceptions after lower-extremity revascularization surgery.
      The MOS-36 has a scale that measures life health concepts and a health-transition
      item. The purpose of this study was to determine the effect of lower-extremity
      revascularization on the quality of life in limb-threatened patients. The study
      examined quality of life as an outcome after revascularization.

PMID- 9258024
TI  - The use of arm vein as an alternative conduit for lower-extremity bypass.
AB  - A 4-year retrospective review of all cases utilizing arm vein for lower-extremity
      bypass was undertaken. Thirty-six cases were reviewed. The patients had portions
      of the basilic or cephalic arm veins, or both, harvested and used as a bypass for
      limb salvage. Composite grafts using a portion of arm vein were excluded.
      Information on demographics, risk factors, vascular surgical history, presenting
      signs and symptoms, surgical complications, patient comfort (arm vs. leg pain),
      and patency rates was studied. We found that all patients were initially seen
      with claudication or rest pain, that 22% had gangrenous changes, that there was a
      male dominance (75%), and that all had previous coronary artery bypass grafts or
      lower-extremity bypass. Limb salvage rate was 85% at 4 years. Primary patency
      rate was 71% at 4 years. We conclude that arm vein is a useful and durable
      conduit for bypass. Patient acceptance and comfort is high.

PMID- 9258025
TI  - General information on the USCF endovascular AAA treatment program.

PMID- 9258026
TI  - March madness.

PMID- 9258027
TI  - Road to rehabilitation.

PMID- 9258028
TI  - Speared by a single spine.

PMID- 9258030
TI  - Smoking out bad habits.

PMID- 9258029
TI  - AIDS and HIV--the worldwide nursing challenge.

PMID- 9258032
TI  - Life from death. Interview by Janet Snell.

PMID- 9258031
TI  - The ultimate gift.

PMID- 9258033
TI  - No time to lose. Interview by Alison Whyte.

PMID- 9258034
TI  - Know how--female catheterisation.

PMID- 9258035
TI  - The shape of things to come.

PMID- 9258036
TI  - From victims to allies.

PMID- 9258038
TI  - Taken to court.

PMID- 9258037
TI  - Ready, teddy, go. Interview by Janet Snell.

PMID- 9258039
TI  - How nurses can support people with epilepsy.
AB  - This article looks at the nurse's role in caring for people with epilepsy in
      different age groups and at new developments in the treatment of this condition.
      A previous article (Nursing Times, May 21) looked at the diagnosis of epilepsy
      and the management of seizures.

PMID- 9258040
TI  - What is meant by woman-centred care?

PMID- 9258041
TI  - The effects of multiple medication in the elderly.
AB  - This article is the first of two looking at medication-related problems in the
      elderly. The processes through which drugs are handled by the body are briefly
      described and common problems associated with medication and the elderly are
      discussed. A case study is presented to illustrate some of these issues. The
      second article on this subject will appear in next week's Nursing Times.

PMID- 9258042
TI  - Benefits of new legislation for moving and handling.

PMID- 9258043
TI  - A steep learning curve for teachers.

PMID- 9258044
TI  - Survival and beyond: challenges in the 1990s.

PMID- 9258045
TI  - Ebonics and psychotherapy.

PMID- 9258046
TI  - Power and leadership in psychiatric nursing: directions for the next century.
      Part II.
AB  - TOPIC: The application of power and leadership to psychiatric nursing in the next
      century PURPOSE: To suggest strategies for empowering psychiatric nursing.
      SOURCE: Review of the literature and authors observations of the discipline
      CONCLUSIONS: Empowerment of our discipline rests with individuals committed to
      changing the societal problems holding us back. This will be accomplished through
      consciousness-raising, coalition-building, transformation, feminist leadership,
      political action, public relations, development of a new language, and research.

PMID- 9258047
TI  - The male experience of depression.
AB  - TOPIC: Men's lived experience of depression METHODS: A qualitative study using
      grounded theory (N = 14). FINDINGS: The men interviewed experienced rigid,
      traditional role identities; expectations related to performance; emotional
      distance from others; the loss of control; the hidden self; depression as a
      force; substance use and abuse; suicide as a means of taking control; and late
      entry into treatment. CONCLUSION: Beliefs about being male are challenged by the
      illness, and challenge the process of treatment and recovery.

PMID- 9258048
TI  - Milieu therapy: a therapeutic loophole.
AB  - TOPIC: The confusion over, and ultimate demise of, milieu therapy. SOURCE:
      Literature review. GOAL: To chronicle the conceptual problems and other events
      leading to the decline in the use of milieu therapy. CONCLUSION: Inpatient nurses
      would do best to leave the concept of milieu therapy behind and focus on
      clarifying how specific nursing interventions are operationalized and tied to
      patient outcomes.

PMID- 9258049
TI  - Life, death, and rebirth: images of transformation and renewal in dreams.

PMID- 9258050
TI  - News from the International Organization of Psychotherapists in Nursing (IOPN)
      and the Network of New York Clinical Specialists in Psychiatric-Mental Health
      Nursing.

PMID- 9258051
TI  - Aging and the problem of urinary incontinence: AHCPR's 1996 clinical practice
      guidance.

PMID- 9258052
TI  - Collagen injections in difficult cases of stress urinary incontinence: study
      results.

PMID- 9258053
TI  - Effect of transvaginal stimulation in the treatment of detrusor instability.
AB  - INTRODUCTION: Early research on implantable electrodes for transvaginal
      stimulation had high rates of complications and mechanical failures. Today's
      nonimplantable devices are safe for short-term or long-term use. This study
      evaluated an intermittent short-term transvaginal stimulation program for
      treatment of bladder overactivity. METHODS: Fifteen women who ranged in age from
      22 to 96 years and had bladder instability were enrolled into this noncontrolled,
      open, clinical evaluation program. Six to 10 biweekly office sessions were
      followed by use of a home unit twice daily for approximately 6 weeks. RESULTS:
      Results were based on patients' voiding diaries. All 15 completed the study, and
      73% were satisfied with the results. On pretrial urodynamic examination nine
      patients had sensory urgency, and six patients had involuntary contractions. All
      tolerated therapy without side effects. Two women had slight vaginal discomfort
      because of vaginal narrowing. Urinary frequency, urgency, and nocturia were
      significantly decreased. Seven women reported 75% or more improvement; four women
      reported 50% to 75% improvement. Three women required a second office treatment
      series. DISCUSSION: The results of this study support findings of previous
      researchers, although the follow-up time frame of the study was short. Most of
      these patients (N = 11 of 15) wished to continue transvaginal stimulation. When
      three women discontinued home treatments, symptoms recurred in 1 to 3 months. The
      exact cause is unclear, but scar tissue as a result of previous pelvic operations
      may have contributed to the problem. The second course of treatment had positive
      results. Intermittent therapy in these cases is recommended. Transvaginal
      stimulation should be considered for treatment for urinary incontinence because
      the device is easily used and adjusted by the patient, patients may be very
      compliant, and results are satisfactory and at least similar to those attained
      with drug therapy.

PMID- 9258054
TI  - Using the Internet for urology nursing.
AB  - Nurses can take advantage of the Internet for information on diseases, diagnosis,
      and treatment, patient teaching, and collaboration with colleagues. The Internet
      is briefly described in this article. Several specific Internet addresses are
      given. Issues such as quality of resources, confidentiality and privacy,
      professional licensure and reimbursement of services rendered, and cost are
      discussed. Search tools for finding information you want on the Internet are
      included.

PMID- 9258055
TI  - Patient selection criteria for treatment of urinary incontinence with pelvic
      floor stimulation.
AB  - This article describes a comprehensive assessment used at the authors'
      institutions for women with urinary incontinence who want to try pelvic floor
      stimulation. Physiologic, cognitive, psychosocial, and affective parameters are
      included. There are factors in each of these areas that contribute to the success
      or failure of pelvic floor stimulation as a treatment. Voiding diaries and visual
      analog scales are used to measure baseline and treatment progress. The authors
      recommend a 7-day diary before treatment and continuance of a diary for 3 to 4
      months. A Patient Response Chart is presented that helps patients to report
      severity of symptoms. Patients would objectively show a decrease in incontinence
      episodes. Subjective improvement should also occur because patient satisfaction
      and quality of life are the ultimate goals of treatment.

PMID- 9258056
TI  - Nurses' perceptions of urinary catheter selection and management.
AB  - Nurses are often responsible for the initiation of catherization procedures for
      patients within the hospital or community setting. This nursing role requires
      contemporary information on catheter selection and problem solving in the
      maintenance of urinary catheters. A descriptive survey with a questionnaire sent
      to registered and enrolled nurses (N = 709) within an Australian metropolitan
      area health service was undertaken to determine their current knowledge level in
      relation to catheter care practices. Registered nurses represented 91% of the
      sample, with 66% of the entire sample having 7 or more years of nursing
      experience. Only 14% of nurses believed that their knowledge levels were
      adequate, with very few receiving postregistration education. Only 31% of the
      respondents recommended the use of purely silicone catheters, these being the
      least cytotoxic to the urethra for longterm use. Less than half of the
      respondents were unaware of the availability of female-length catheters. There
      was a general lack of knowledge of current catheter costs that would have major
      implications for unit budgets. The apparent gaps in nursing knowledge of catheter
      care suggest the need for urgent educational programs on catheter care practices
      for nurses within this service and the initiation of an area-wide standardized
      policy in catheter selection and management.

PMID- 9258057
TI  - A new framework for urinary continence outcomes in long-term care.
AB  - Careful assessment and individual care planning are especially important when
      approaching the problems of incontinence in long-term care patients.
      Identification of appropriate interventions and desired outcomes is assuming
      greater prominence. This article provides an overview of some of the issues that
      affect incontinence with long-term patients and presents a refined concept of
      several classifications of incontinence that direct approaches to care. The
      classifications are based on whether a patient is dependent or independent on a
      caregiver to achieve continence. Assumptions, goals, and evidence for
      effectiveness of these interventions are discussed for the four classifications.
      Further implications for nursing are also addressed.

PMID- 9258058
TI  - "Homemade" lidocaine gel.

PMID- 9258059
TI  - Phenazopyridine hydrochloride: information for patient teaching.

PMID- 9258060
TI  - CBUNA celebrates 25 years. Certification Board for Urologic Nurses and
      Associates.

PMID- 9258061
TI  - This month in investigative urology. L-arginine and penile erection.

PMID- 9258062
TI  - Update on the appropriate staging evaluation for newly diagnosed prostate cancer.
AB  - PURPOSE: Prostate cancer clinical staging methods and decision support tools were
      reviewed to assess their accuracy to predict pathological staging results and
      determine what comprises an appropriate clinical staging evaluation. MATERIALS
      AND METHODS: The MEDLINE data base was searched and 238 abstracts were obtained.
      Data were extracted from 142 articles that evaluated the preoperative accuracy of
      digital rectal examination, prostate specific antigen, prostatic acid
      phosphatase, systematic biopsy parameters (including Gleason scoring), seminal
      vesicle biopsy, various imaging studies and pelvic lymphadenectomy versus
      pathological staging results. The sensitivity, specificity and accuracy rates
      were calculated and tabulated from the reported data on each method or decision
      support tools for organ confined, nonorgan confined and lymph node metastatic
      tumor. RESULTS: Decision support tools based on logistic regression analysis,
      which combine several statistically independent staging parameters, had greater
      accuracy than any single clinical staging method alone. The most accurate
      decision support tools for clinical staging combined digital rectal examination
      (T stage), systematic biopsy parameters (including Gleason scoring) and prostate
      specific antigen. CONCLUSIONS: The components that comprise the most accurate
      decision support tools for clinical staging represent an appropriate staging
      evaluation for the newly diagnosed prostate cancer patient in 1997. Limited use
      of radiographic imaging and seminal vesicle biopsy may be indicated in select
      patients to detect bone metastases, and plan pelvic lymphadenectomy and surgical
      therapy.

PMID- 9258063
TI  - Floating kidneys: a century of nephroptosis and nephropexy.
AB  - PURPOSE: Recently trained physicians are often unfamiliar with nephroptosis.
      Nephropexy, once a routine operation, almost disappeared from American practice
      more than 2 decades ago. In view of a recent revival of interest in nephroptosis
      and nephropexy in the American urological literature, a historical overview of
      nephroptosis and the evolution of surgical nephropexy is timely. MATERIALS AND
      METHODS: A National Library of Medicine data base (1966 to 1996) search of
      "nephroptosis," "nephropexy" and "Dietl's crisis" was performed. Textbooks and
      monographs from the last 100 years were consulted. Original clinical descriptions
      and surgical accounts dating back more than 130 years were traced and reviewed.
      RESULTS: Nephroptosis and nephropexy have been subjects of controversy since
      Edebohls in New York popularized nephropexy in 1893. A close association with
      "neurasthenia" clouded objectivity prior to 1920. Nearly 200 surgical procedures
      were described. Urological opinion was often sharply polarized. In the last 2 to
      3 decades the subject was largely eclipsed in the United States. Recently,
      however, new laparoscopic surgical techniques have been applied to the treatment
      of symptomatic nephroptosis. CONCLUSIONS: Few diagnoses and surgical procedures
      have had such a contentious and colorful history. It seems likely that new
      criteria for diagnosis of symptomatic nephroptosis and the introduction of
      laparoscopic nephropexy will lead to renewed interest in the subject among
      generalists and specialists. Knowledge of the current literature can be enriched
      by an overview of the events of the last century.

PMID- 9258064
TI  - Improvement in interstitial cystitis symptom scores during treatment with oral L
      arginine.
AB  - PURPOSE: Urinary nitric oxide synthase activity is decreased in patients with
      interstitial cystitis. Since nitric oxide may be an important determinant of the
      symptoms and immunological responses associated with interstitial cystitis,
      patients with this disease were treated with oral L-arginine, the substrate for
      nitric oxide synthase. MATERIALS AND METHODS: Ten patients took 1.5 gm. L
      arginine orally daily for 6 months. Interstitial cystitis symptoms were surveyed
      before and during the 6-month trial. RESULTS: Oral L-arginine treatment resulted
      in a significant decrease in urinary voiding discomfort, lower abdominal pain and
      vaginal/urethral pain. Urinary frequency during the day and night also
      significantly decreased. CONCLUSIONS: This self-controlled study provides
      evidence that long-term oral L-arginine improves interstitial cystitis related
      symptoms.

PMID- 9258065
TI  - Ureterorenoscopic approach to the symptomatic caliceal diverticulum.
AB  - PURPOSE: We evaluated ureterorenoscopy as a treatment approach to symptomatic
      caliceal diverticula. MATERIALS AND METHODS: Since 1989, 20 women and 6 men
      suffering from pain, recurrent urinary tract infections or urosepsis were treated
      using flexible ureterorenoscopy, balloon dilation or incision of the diverticular
      neck and subsequent intrarenal stone fragmentation when needed. RESULTS: Of 19
      upper and middle caliceal diverticula 16 (84%) and 2 of 7 lower caliceal
      diverticula were successfully identified. The orifice to the diverticular cavity
      was dilated and the stone was fragmented. Of the patients 13 were treated as
      outpatients and 10 required a 1-night hospital stay. Of those patients in whom
      the diverticulum could be entered and the stone fragmented 100% were symptom-free
      at a mean followup of 39 months. One patient required repeat treatment to remove
      residual stone. CONCLUSIONS: Ureterorenoscopy produces minimal morbidity and is
      an effective treatment of upper and middle caliceal diverticula.

PMID- 9258066
TI  - Assessment of preservation induced reperfusion injury via intraoperative renal
      transplant blood flow and endothelin concentration studies.
AB  - PURPOSE: We investigated a possible relationship between levels of the
      vasoconstrictive peptide endothelin and renal transplant reperfusion injury, and
      modified a technique for measuring renal blood flow with an ultrasonic
      perivascular transit time flow probe. MATERIALS AND METHODS: Renal grafts in a
      swine transplant model were cold flushed with either Collins-2 or University of
      Wisconsin solution. Renal blood flow and renal vein endothelin levels after
      reperfusion of transplanted grafts, as well as histological parameters within the
      transplanted kidney were measured. The 5-minute post-reperfusion renal blood flow
      was used as the baseline allograft flow. The definition of reperfusion injury was
      a decrease in flow from baseline with no recovery within 1 hour of reperfusion.
      In 9 human recipients reperfusion injury was further verified by monitoring
      subsequent serum creatinine, urine output, graft survival and rejection episodes.
      RESULTS: In the swine model and human transplant recipients no evidence of post
      reperfusion ischemia was noted by histological examination, supporting that
      moderate to mild reperfusion injury or ischemic injury cannot be clinically
      determined with this method. In the swine model the decrease flow from baseline
      in allograft post-reperfusion renal blood flow was significantly greater in
      kidneys preserved in Collins'-2 than in University of Wisconsin solution (41.75
      +/- 5.69 versus 11.18 +/- 13.99 ml. per minute, p = 0.005), supporting that this
      technique can assess mild to moderate reperfusion injury. The increase in serum
      endothelin in the allografts from the swine model and in humans was not
      significantly different from baseline. Clinically, post-reperfusion renal blood
      flow changes correlated well with subsequent function. The 4 patients with renal
      transplant reperfusion injury had significantly higher serum creatinine values
      and lower urine output 1 week postoperatively than 5 patients with no evidence of
      injury (serum creatinine: 6.75 +/- 3.03 versus 2.08 +/- 1.28 mg./dl., p = 0.015).
      Reperfusion injury patients had more rejections (2 versus 1) and less graft
      survival (75% versus 100%) at 1-year followup compared to the nonreperfusion
      injury patients. CONCLUSIONS: Vasoactive factors other than endothelin most
      likely contribute to reperfusion injury. Furthermore, the ultrasonic transit time
      flow probe accurately measures post-reperfusion renal blood flow and offers a
      practical method for assessing acute reperfusion injury, which may help to
      optimize immunosuppressive strategies to decrease allograft loss associated with
      delayed graft function.

PMID- 9258067
TI  - Laparoscopic radical nephrectomy: the Nagoya experience.
AB  - PURPOSE: We evaluated the efficacy of laparoscopic radical nephrectomy for
      removing kidneys with small volume renal cell carcinoma. MATERIALS AND METHODS:
      25 patients (19 men and 6 women, mean age 59) who had a kidney with small volume
      renal cell carcinoma (diameter less than 5 cm.), underwent laparoscopic radical
      nephrectomy. The kidney was dissected laparoscopically together with the adrenal
      gland, perirenal fatty tissue and Gerota's fascia. In 11 patients, we used the
      transperitoneal approach and in the remaining 14 we used the retroperitoneal
      approach, in which a working space is created by finger and balloon dissection.
      We maneuvered the kidney into the laparoscopy sack, which was then removed
      through an additional 5 to 6 cm. incision. RESULTS: All 25 kidneys were removed
      successfully. Mean operation time was 5.3 hours and mean estimated blood loss was
      335 ml. There were 5 complications, including a patient who suffered an injury to
      the duodenum, which was treated by open duodenojejunostomy. Full convalescence
      occurred at an average 23 days. No metastatic disease, no local recurrence and no
      seeding at the port sites occurred during the followup of 7 to 49 months (mean,
      22 months). CONCLUSIONS: Laparoscopic radical nephrectomy is recommended as a
      minimally invasive procedure for removing kidneys with small volume renal cell
      carcinoma.

PMID- 9258068
TI  - C-met proto-oncogene expression in benign and malignant human renal tissues.
AB  - PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen to
      renal epithelial cells in vitro and in vivo. HGF/SF signals through its receptor
      which is coded by the c-met proto-oncogene. We hypothesized that altered
      expression of the HGF/SF receptor, c-met, may be involved in the pathogenesis of
      certain renal cell carcinomas. Our objectives were to 1) assess the presence and
      localization of c-met protein in benign and malignant human renal tissues, and 2)
      correlate the presence of c-met protein with renal carcinoma histological
      subtype, tumor stage and tumor grade. MATERIALS AND METHODS: Immunohistochemical
      analysis of c-met protein was performed in 41 normal and malignant human renal
      samples. RESULTS: c-met Immunostaining was detected in the normal kidney tissue
      in all 41 samples. In the normal kidney c-met immunostaining was limited to the
      cell membrane and/or cytoplasm of epithelial cells in specific tubular segments,
      including the proximal convoluted tubule, thin and thick limbs of the loop of
      Henle, and the collecting duct. The glomeruli, distal convoluted tubule and
      stroma were consistently negative for c-met staining. c-met Immunostaining was
      detected in 68% of renal cell carcinomas and was more common in higher nuclear
      grade cancers (p < 0.034). CONCLUSIONS: The c-met receptor is present in specific
      tubular segments in the normal kidney and is frequently expressed in higher
      nuclear grade renal cancers, suggesting a role in renal carcinoma progression.
      Future studies should evaluate the biological significance of the HGF/ SF-c-met
      pathway in normal renal physiology, and renal cancer growth and progression.

PMID- 9258069
TI  - The impact of tumor size on clinical outcome in patients with localized renal
      cell carcinoma treated by radical nephrectomy.
AB  - PURPOSE: We investigated the influence of tumor size on clinical outcome in
      patients with localized renal cell carcinoma treated with radical nephrectomy.
      MATERIALS AND METHODS: We reviewed retrospectively the records of 54 patients
      with pathological T1, T2 renal cell carcinoma for age, sex, histological grade,
      cell type, architecture, deoxyribonucleic acid ploidy pattern, nuclear
      morphometry and vimentin expression. Variables found to predict outcome were
      correlated with tumor size, which was further tested for its prognostic value.
      RESULTS: The best predictors of prognosis were grade, ploidy pattern, nuclear
      morphometry and vimentin expression. Small (less than 5 cm.) and large (larger
      than 5 cm.) tumors had similar distribution of prognostic variable subgroups. No
      differences in progression rate or survival were noted between the tumor size
      categories. CONCLUSIONS: These results suggest that small renal tumors may follow
      unfavorable courses and require aggressive treatment.

PMID- 9258070
TI  - Hypercalcemia in patients with metastatic renal cell carcinoma: effect of
      nephrectomy and metabolic evaluation.
AB  - PURPOSE: The role of nephrectomy in the management of hypercalcemia in metastatic
      renal carcinoma is not known. Hypercalcemia in patients with renal cell carcinoma
      frequently mimics primary hyperparathyroidism and has been attributed to tumor
      secretion of parathyroid hormone related protein. We determined the role of
      cytoreductive surgery in patients with metastatic renal cell carcinoma and
      hypercalcemia, identified factors that predict patient benefit from surgery, and
      evaluated the mechanisms of hypercalcemia in these patients. MATERIALS AND
      METHODS: A total of 15 patients with metastatic renal cell carcinoma and
      hypercalcemia underwent metabolic and laboratory evaluation followed by
      nephrectomy. Post-operatively they were followed for changes in serum calcium
      levels. We selected 18 normocalcemic patients with metastatic renal cell
      carcinoma and 4 normocalcemic patients without renal cancer to serve as control
      groups for survival and parathyroid hormone related protein expression. RESULTS:
      A decrease in serum calcium corrected for albumin occurred in 9 of 11 patients at
      1 to 4 weeks after nephrectomy and in 7 of 12 patients at 5 to 16 weeks after
      nephrectomy. Clinical evaluation supported a parathyroid hormone related protein
      mechanism of hypercalcemia in 5 of 8 patients. Two patients had evidence of local
      osteolytic hypercalcemia and 1 had prostaglandin mediated hypercalcemia.
      CONCLUSIONS: Nephrectomy temporarily ameliorated hypercalcemia in a subgroup of
      patients with metastatic renal cancer and hypercalcemia. Parathyroid hormone
      related protein expression was commonly found to be associated with
      hypercalcemia. Nonparathyroid hormone related protein mechanisms of hypercalcemia
      in renal carcinoma may be more common than previously thought.

PMID- 9258071
TI  - Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and
      cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary
      tumor.
AB  - PURPOSE: Metastatic renal cell carcinoma is a disease with a mean survival of 6
      to 10 months. Interleukin-2 (IL-2), the only approved therapy for metastatic
      renal cell carcinoma, is associated with a 14% response rate and durable
      remissions in some patients with high performance status. We performed a series
      of trials of IL-2 plus tumor infiltrating lymphocyte cell therapy and report the
      clinical results from 62 patients enrolled in these trials. MATERIALS AND
      METHODS: Patients were eligible if they had metastatic renal cell carcinoma with
      the primary tumor in place and an Eastern Cooperative Oncology Group performance
      status of 0 or 1. Patients were treated with cytokines before nephrectomy and
      preparation of cytokine primed tumor infiltrating lymphocytes or CD8(+) tumor
      infiltrating lymphocytes were isolated for infusion into patients. Of 62 patients
      enrolled 55 were treated with tumor infiltrating lymphocytes and IL-2, and were
      evaluable for toxicity, response and survival. RESULTS: There were no
      postoperative mortalities. Of the patients 7 (11%) could not undergo systemic
      therapy. No unexpected IL-2 related toxicities or significant toxicities related
      to cell infusion were noted. Overall 5 patients (9.1%) achieved a complete
      response and 14 (25.5%) achieved a partial response. The responses were durable
      with a median duration of 14 months (range 0.8+ to 64+). The actuarial survival
      was 65% at 1 year and 43% at 2 years from the time of nephrectomy, with an
      overall median survival for all patients of 22 months (range 2 to 70+). The
      median survival for the responding patients has not yet been reached (range 2 to
      63+). CONCLUSIONS: These results demonstrate that immunotherapy with radical
      nephrectomy, tumor infiltrating lymphocytes, and IL-2 provides substantial
      clinical benefit in the majority of patients. Component cellular therapy with
      enriched cell fractions allows the administration of a more standardized cell
      product. The present results with nephrectomy, tumor infiltrating lymphocytes and
      IL-2 are encouraging, and a randomized clinical trial of nephrectomy, CD8(+)
      tumor infiltrating lymphocytes, plus IL-2 versus nephrectomy and IL-2 alone is
      currently in progress.

PMID- 9258072
TI  - Palliative irradiation for focally symptomatic metastatic renal cell carcinoma:
      support for dose escalation based on a biological model.
AB  - PURPOSE: Renal cell carcinoma has traditionally been regarded as a radioresistant
      cancer, yet controversy continues as to whether escalation of the palliative
      radiation dose can overcome the inherent resistance of such tumors when they
      metastasize. Recently, the linear quadratic model has emerged as a paradigm to
      assess biologically effective dose of radiotherapy. This study was undertaken to
      determine the ability of radiotherapy to palliate focally symptomatic metastatic
      renal cell carcinoma and to assess whether the delivery of higher biologically
      effective dose was more likely to bring about a palliative response. MATERIALS
      AND METHODS: Between 1966 and 1995, 107 patients with renal cell metastases at
      150 sites were irradiated with palliative intent. Sites irradiated included bone
      (89), soft tissue (16), brain (20), spinal cord (9) and pulmonary (16). To
      determine dose effectiveness the biologically effective dose was calculated
      according to the formula, Gy10 = total dose (1 + fractional dose/alpha-beta),
      using an alpha-beta of 10. RESULTS: For the entire group 86% of patients derived
      a palliative response after treatment with irradiation, while 49% derived a
      complete palliative response. The median duration of palliation was 6 months
      (range 1 to 150). With respect to overall (that is, complete and partial)
      response rates, those presenting with high Karnofsky performance status were most
      likely to respond (status 70 or greater versus less than 70, 88% versus 78%, p <
      0.04). With respect to the rate of complete palliative response, performance
      status (status 70 or greater versus less than 70, 55% versus 31%, p < 0.03) and
      the use of higher biologically effective doses of irradiation (Gy10 50 or greater
      versus less than 50, 59% versus 39%, p = 0.001) were associated with a
      statistically significant increased rate of response. The independent prognostic
      value of performance status and higher biologically effective doses of
      irradiation were maintained in multivariate analysis. CONCLUSIONS: Despite the
      prevailing concept that renal cell carcinoma is generally resistant to
      radiotherapy, the overwhelming majority of patients seen at our institution in
      whom metastatic renal cell carcinoma developed were palliated with radiotherapy.
      A complete palliative response is more likely when higher biologically effective
      doses of irradiation are delivered, especially to patients with a relatively high
      performance status.

PMID- 9258073
TI  - Apoptosis in transitional cell carcinoma of the renal pelvis and ureter:
      association with proliferative activity, bcl-2 expression and prognosis.
AB  - PURPOSE: We attempted to clarify the significance of apoptosis in tumor
      development and progression in 64 cases of transitional cell carcinoma of the
      renal pelvis and ureter by investigating apoptosis, proliferative activity and
      bcl-2 expression. MATERIALS AND METHODS: We used in situ deoxyribonucleic acid
      nick end labeling for apoptotic cells and immunohistochemical staining for bcl-2
      on archival tumor material. RESULTS: The apoptotic index correlated significantly
      with mitotic index, histological grade and pathological stage. There was no
      significant relationship between apoptotic index and bcl-2 expression. Patients
      with an apoptotic index greater than or equal to 0.22 had a poor prognosis.
      CONCLUSIONS: Apoptosis is closely related to proliferative activity, tumor
      differentiation and depth of invasion in transitional cell carcinoma of the renal
      pelvis and ureter.

PMID- 9258074
TI  - Diagnosis and management of ureteroiliac artery fistula: value of provocative
      arteriography followed by common iliac artery embolization and extraanatomic
      arterial bypass grafting.
AB  - PURPOSE: We describe an effective multidisciplinary approach to the diagnosis and
      management of ureteroarterial fistulas that reduces morbidity and mortality.
      MATERIALS AND METHODS: Five ureteroarterial fistulas in 4 patients were studied
      with standard and provocative arteriography (arteriography combined with ureteral
      manipulation). After establishing the diagnosis, each lesion was treated with
      percutaneous embolic occlusion of the common iliac artery followed by
      extraanatomic arterial bypass grafting. All patients had chronic ureteral
      stenting, prior pelvic irradiation, prior pelvic surgery and intrapelvic
      malignancy, and all fistulas presented with urinary tract hemorrhage. RESULTS:
      Standard arteriography was nondiagnostic but provocative arteriography
      demonstrated the fistula in each case. Successful embolization of the common
      iliac artery followed by extraanatomic arterial bypass grafting precluded the
      need for laparotomy and preserved ipsilateral renal function. CONCLUSIONS:
      Provocative arteriography followed by arteriographic common iliac artery
      embolization and extraanatomic bypass grafting was successful for the diagnosis
      and treatment of ureteroarterial fistulas. There was no mortality, limb loss or
      renal loss.

PMID- 9258075
TI  - Long-term results of endoureterotomy for benign ureteral and ureteroenteric
      strictures.
AB  - PURPOSE: We reviewed the results of endoureterotomy for benign ureteral and
      ureteroenteric strictures to determine efficacy and factors associated with a
      successful outcome. MATERIALS AND METHODS: Followup was available for 69 patients
      undergoing 77 endoureterotomies. Success was defined as symptomatic improvement
      and radiographic resolution of obstruction. Kaplan-Meier survival curves were
      constructed and data were analyzed with a Cox proportional hazards model.
      RESULTS: None of 9 procedures in patients with the ipsilateral kidney
      contributing less than 25% of total renal function was successful. Among the 38
      remaining benign ureteral stricture treatments with ipsilateral function 25% or
      greater with a median followup of 28.4 months among successful cases the 3-year
      success rate was 80%. No procedure failed beyond 11 months and there were 25
      patients at risk beyond this point. Among the 30 remaining ureteroenteric
      stricture treatments with ipsilateral function 25% or greater the success rates
      at 1, 2 and 3 years were 73, 51 and 32%, respectively. Failures were noted during
      the first 36 months but none occurred later and 5 patients were at risk beyond
      this point. Overall, complete or tight strictures were less successfully treated.
      A nonischemic etiology, a stent 12F or greater and injection of triamcinolone
      into the bed of the incised stricture were associated with better outcome for
      strictures longer than 1 cm. CONCLUSIONS: Endoureterotomy of benign ureteral
      strictures is associated with an excellent outcome (80% success at 3 years).
      Endoscopic treatment of ureteroenteric strictures is less successful but still
      offers a reasonable first step (32% 3-year success rate). For all strictures
      failure is likely if ipsilateral renal function is poor. For strictures longer
      than 1 cm. use of a stent 12F or greater and injection of triamcinolone appear to
      be beneficial.

PMID- 9258076
TI  - Ureteroileal implantation in orthotopic neobladder with the Le Duc-Camey mucosal
      through technique: risk of stenosis and long-term follow-up.
AB  - PURPOSE: We determined the postoperative risk of nonneoplastic ureteroileal
      implantation stenosis using the Le Duc-Camey technique, and assessed the extent
      to which followup is mandatory. MATERIALS AND METHODS: Between October 1980 and
      October 1989, after a cystoprostatectomy, 158 consecutive men underwent lower
      urinary tract reconstruction by means of a U-shaped orthotopic ileal neobladder.
      Of these cases 109 were tubularized and 49 were detubularized. The 313 ureteral
      implantations were performed according to the Le Duc-Camey mucosal-through
      technique. Followup studies in all patients consisted of excretory urography or
      renal sonography carried out before discharge home, at least every 6 months
      during the first year after surgery and once a year thereafter. Followup was more
      than 2 years for 123 patients. The study was conducted retrospectively. RESULTS:
      The rate of anastomotic stenosis was 4.9% among 123 patients who were followed a
      minimum of 2 years. No obstructions were detected after 2 years. The rates of
      ureteral reimplantation and nephrectomy for chronic kidney obstruction were 3.7%
      and 2%, respectively. All strictures were located at the anastomosed site, and
      retrograde catheterization was uncertain. Surgical reimplantation through an
      elective extraperitoneal approach was easy to perform and effective. CONCLUSIONS:
      The anastomotic stenosis rate after Le Duc-Camey ureteroileal implantation in
      orthotopic U-shaped neobladder was 4.9%. During the first year after surgery, the
      difference between true stenosis and temporary edema was not easy to assess. The
      U-shaped neobladder allows for the implantation of a minimally dissected iliac
      ureter, which could be a factor in minimizing the risk of obstruction.

PMID- 9258077
TI  - Ureteral carcinoma in situ at radical cystectomy: does the margin matter?
AB  - PURPOSE: The clinical impact of ureteral carcinoma in situ identified at the time
      of radical cystectomy for bladder cancer has been poorly studied. We discuss our
      experience with this clinical problem in the context of published reports.
      MATERIALS AND METHODS: A total of 31 patients with concomitant ureteral carcinoma
      in situ was retrospectively identified among 401 consecutive radical
      cystectomies. End points analyzed included positive urinary cytology, upper tract
      recurrence of carcinoma and cancer specific survival. RESULTS: Ureteral margins
      were positive in 21 patients and negative in 10. Among 30 patients in whom it was
      performed frozen section failed to detect carcinoma in situ in 5 (16.6%) and
      sequential ureteral resection did not result in a negative margin in 15 (50%). In
      3 patients upper tract carcinoma recurred at the anastomosis (1) and renal
      pelvis/ureter (2) at a median of 51 months (mean 49, range 36 to 59) following
      cystectomy. Positive cytology and upper tract carcinoma recurrence were not
      significantly associated with ureteral margin status, clinical or pathological
      bladder tumor stage or prior bacillus Calmette Guerin treatment. Median followup
      was 22.9 months (mean 31.8, range 2.0 to 74.2), during which 7 of the 31 patients
      died of metastatic bladder cancer. CONCLUSIONS: Concomitant ureteral carcinoma in
      situ is uncommon, and is rarely associated with local morbidity. It appears to
      confer increased risk for upper tract carcinoma recurrence, irrespective of
      margin status. In our experience upper tract carcinoma recurrence is heralded by
      positive cytology and generally appears only with protracted followup. Prognosis
      appears to be determined by the bladder tumor. Given the lack of morbidity and
      mortality attributable to concomitant ureteral carcinoma in situ, and the limited
      ability of frozen section examination to assist in its extirpation, the value of
      intraoperative identification of concomitant ureteral carcinoma in situ is
      questionable and expectant management is advised.

PMID- 9258078
TI  - Routine stentograms are not necessary before stent removal following radical
      cystectomy.
AB  - PURPOSE: Although ureteral stents have significantly reduced perioperative
      complications of urinary diversion, there is no universal agreement regarding
      their postoperative management. As part of an effort to eliminate unnecessary
      studies and hospital costs for radical cystectomy, we recently reviewed our
      experience with postoperative radiological stent studies to determine their
      clinical use and cost. MATERIALS AND METHODS: A retrospective examination of
      medical records and radiographic studies was performed for 96 patients undergoing
      cystectomy and urinary reconstruction between 1989 and 1996. All patients were
      stented at the time of surgery. Of the patients 51 underwent bilateral retrograde
      "stentograms" performed under fluoroscopic guidance before stent removal to
      evaluate for obstruction or urine leak as dictated by the preference of the
      primary surgeon in each case. A total of 41 evaluable patients did not undergo
      stentograms. RESULTS: In this study 102 stent injections were performed on 51
      patients before stent removal. No patients were found to have ureteral
      obstruction at the ureterointestinal anastomosis, while 1 (0.98%) had a
      clinically silent anastomotic leak that healed with conservative measures.
      Complications directly attributable to the stent studies, including episodes of
      urosepsis, were noted in 9 patients (17.6%). Nine additional leaks were diagnosed
      in this cohort by other means. Half of all leaks were evident clinically and 60%
      of this group required further invasive procedures. All clinically silent leaks
      healed with conservative measures. Of 41 evaluable patients who did not undergo
      stentograms leak following stent removal developed in only 2 and both healed with
      conservative measures. The additional cost of detecting a single anastomotic leak
      with routine stentograms is estimated to be $58,000. CONCLUSIONS: Routine
      evaluation of the ureterointestinal anastomosis with stentograms before stent
      removal is unnecessary, costly and may in fact increase patient morbidity.

PMID- 9258079
TI  - Efficacy of retrograde stentograms following cystectomy and diversion.
AB  - PURPOSE: The radiological evaluation of ureteroenteric anastomoses following
      cystectomy and diversion is standard practice at our institution. To our
      knowledge there are no data that demonstrate the efficacy of retrograde
      "stentograms" following cystectomy. MATERIALS AND METHODS: A retrospective
      analysis of the retrograde stentograms of 73 patients who underwent cystectomy
      and diversion was reviewed. RESULTS: Of 135 ureteroenteric anastomoses 3 (2.2%)
      demonstrated a leak by retrograde stentogram. No patients had evidence of
      obstruction. CONCLUSIONS: The 2.2% incidence of ureteroenteric leak in our series
      does not support the routine use of retrograde stentogram following cystectomy
      and diversion.

PMID- 9258080
TI  - Quality of life after cystectomy and urinary diversion: results of a
      retrospective interdisciplinary study.
AB  - PURPOSE: Now that creation of continent urinary reservoirs has become a
      standardized and clinically well established surgical technique with known
      morbidity and mortality rates, we reassessed the psychological and social aspects
      of this treatment compared with wet urostomy. MATERIALS AND METHODS: We developed
      a questionnaire (102 items) addressing general aspects of quality of life,
      disease related social support, coping strategies and stoma related issues. It
      was mailed to 600 patients with ileal conduits and 130 with continent reservoirs.
      Final analysis was restricted to 192 patients operated upon within the last 5
      years (mean followup 2.7 years). RESULTS: The resulting groups were matched and
      paralleled regarding most treatment related and sociodemographic data. Final
      analysis did not reveal differences between the groups in disease related social
      support, coping strategies or quality of life when expressed as a total score. We
      found statistically significant superiority of continent reservoirs regarding all
      stoma related items, patient global self-assessment of their quality of life
      (single item, p < 0.005), physical strength, mental capacity, leisure time
      activities and social competence (p < 0.05). CONCLUSIONS: Continent diversion is
      clearly advantageous with respect to all items directly related to the stoma. The
      significant superiority of continent diversion in patient global self-assessment
      of their quality of life reflects the highly subjective dimension of the concept.
      Superiority in self-ratings of physical strength, mental capacity, leisure time
      activities and social competence could be interpreted as indicators of enhanced
      vitality in those patients, thus, supporting our understanding that women and men
      who actively participate in life have a special benefit from continent
      reservoirs.

PMID- 9258081
TI  - Excretion of fluorescein in the urine of women with interstitial cystitis.
AB  - PURPOSE: Altered bladder permeability may have a role in the pathogenesis of
      interstitial cystitis. Fluorescein, a fluorescent dye of molecular weight 325,
      has been used to assess membrane permeability. Orally ingested fluorescein
      normally is rapidly conjugated to glucuronate by the liver and excreted in the
      urine. MATERIALS AND METHODS: To test its use as a marker of bladder
      permeability, we administered fluorescein orally to 6 patients with interstitial
      cystitis who satisfied National Institutes of Health, National Institute for
      Diabetes and Digestive and Kidney Diseases criteria and to 6 normal female
      control subjects. After emptying the bladder and collection of a baseline blood
      sample, fasted subjects ingested 20 mg. fluorescein and blood samples were
      collected 1, 2, 3, 4 and 24 hours later. Urine was collected during each of the
      first 4 hours, and then from 4 to 10, 10 to 16 and 16 to 24 hours. Urine volume
      was measured, and all plasma and urine samples were analyzed for fluorescein.
      RESULTS: Plasma fluorescein concentrations (ng./ml.) were significantly (p <
      0.05) higher in interstitial cystitis patients than in control subjects at 1 and
      2 hours after fluorescein ingestion. Urine fluorescein excretion (mg.) was
      significantly (p < 0.05) lower in interstitial cystitis patients than in control
      subjects at 4 to 10 hours after fluorescein ingestion, and for the entire 24
      hours. CONCLUSIONS: The increased fluorescein concentration in the plasma and
      decreased excretion in the urine of interstitial cystitis patients suggest that
      fluorescein may be a useful marker of altered membrane permeability.

PMID- 9258082
TI  - Inflammatory cell types and clinical features of interstitial cystitis.
AB  - PURPOSE: We tested whether the types of inflammatory cells seen on bladder
      biopsies were associated with other clinical features and urinary markers of
      interstitial cystitis. MATERIALS AND METHODS: Bladder biopsies from 30
      interstitial cystitis patients were evaluated by immunohistochemical staining for
      T cells, B cells, macrophages and human leukocyte antigen-DR positive cells.
      These findings were tested for associations with clinical features and urinary
      markers of interstitial cystitis using alpha = 0.01 because multiple tests were
      performed. RESULTS: Overall severity of inflammation was significantly associated
      with age at symptom onset, symptom relief after bladder distention and urinary
      interleukin-6 levels. Patients with severe inflammation had trends toward smaller
      bladder capacity under anesthesia, increased bladder vascularity and mucosal
      cracks, lower urinary MUC-1 glycoprotein levels and absence of bloating as a
      symptom. B cell staining was significantly associated with severe inflammation,
      symptom relief after distention and absence of bloating as a symptom. T cell
      staining was significantly associated with severe inflammation and age at symptom
      onset. Human leukocyte antigen-DR staining had trends with symptoms, including
      presence of bloating, constant urge to void and absence of burning. Macrophage
      staining did not associate with any features tested at the alpha = 0.05 level.
      CONCLUSIONS: Interstitial cystitis patients with severe inflammation have
      different age, treatment response and urinary marker levels than those with mild
      inflammation. These findings suggest that the 2 patient groups have different
      underlying pathophysiologies. The significant associations for T and B cell
      staining were similar to those for overall inflammation.

PMID- 9258083
TI  - Changing concepts in interstitial cystitis.

PMID- 9258084
TI  - 3-dimensional computerized tomographic reconstruction of colovesical fistulas.
AB  - PURPOSE: Use of 3-dimensional tomographic reconstruction in evaluating
      colovesical fistulas is discussed. MATERIALS AND METHODS: We compared 3
      dimensional computerized tomographic (CT) images of colovesical fistulas to
      conventional CT images. RESULTS: Successful surgical repair was facilitated by
      preoperative radiographic data. CONCLUSIONS: Three-dimensional CT reconstruction
      provides superior spacial detail and can clarify complex anatomical relationships
      preoperatively.

PMID- 9258085
TI  - Spontaneous rupture of orthotopic detubularized ileal bladder replacement: report
      of 5 cases.
AB  - PURPOSE: We defined the mechanisms responsible for rupture of orthotopic,
      detubularized ileal bladder replacement. MATERIALS AND METHODS: We reviewed
      retrospectively the records of 5 cases of ileal neobladder rupture treated at our
      center between 1985 and 1995. RESULTS: The interval to perforation varied from 3
      to 60 months after surgery. The perforation site was typically the upper part of
      the right limb of the reservoir. We observed an acute episode of bladder over
      distension immediately before perforation in 2 cases and a chronic state of
      neobladder over distension in the 3 remaining cases. Bacterial infection was
      associated in 4 cases. Intraperitoneal adhesions were an associated mechanism for
      rupture in only 1 case. We found chronic ischemic changes weakening the bladder
      wall to be an additional factor for rupture in the 3 cases associated with
      chronic over distension. CONCLUSIONS: Acute or chronic over distension of the
      neobladder is the main factor for spontaneous rupture of orthotopic detubularized
      ileal bladder replacement. Chronic ischemic changes of the bladder wall, possibly
      facilitated by detubularization and the variability of the mesenteric
      circulation, are additional factors that lead to perforation.

PMID- 9258086
TI  - A multicenter trial evaluation of the fibrin/fibrinogen degradation products test
      for detection and monitoring of bladder cancer.
AB  - PURPOSE: Presently there is a lack of effective, noninvasive tests for the
      detection and monitoring of bladder cancer. Measurement of fibrin/fibrinogen
      degradation products in urine has been shown to be a useful indicator of bladder
      carcinoma. The objective of this study was to evaluate the AuraTek FDP rapid
      immunoassay device for the detection of urinary fibrin/ fibrinogen degradation
      products associated with bladder cancer. MATERIALS AND METHODS: A prospective
      multicenter study was conducted to compare AuraTek FDP with urinary cytology and
      hemoglobin dipstick for the detection of bladder cancer in 192 patients with a
      history of bladder cancer. RESULTS: AuraTek FDP was significantly more sensitive
      (68%) than conventional urinary cytology (34%, p < 0.001) or hemoglobin dipstick
      (41%, p < 0.001) in the detection of bladder tumors, particularly for low stage
      low grade disease. In subjects with invasive disease (T2-T4) the AuraTek FDP test
      had a sensitivity of 100%. Specificity of AuraTek FDP was 96% for healthy
      subjects, 86% in patients with urological disease other than bladder cancer and
      80% for patients under surveillance for bladder cancer but with a negative
      cystoscopic finding at the time of assay. CONCLUSIONS: This simple, rapid (less
      than 7 minutes) point of care test is superior to conventional urine cytology and
      hemoglobin dipstick as an aid in the detection of bladder cancer.

PMID- 9258087
TI  - Deoxyribonucleic acid ploidy enhances the cytological prediction of recurrent
      transitional cell carcinoma of the bladder.
AB  - PURPOSE: We determined whether deoxyribonucleic acid (DNA) ploidy analysis by
      image analysis cytometry enhances the cytological diagnosis of recurrent
      transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A
      retrospective study was performed during a 5-year period to evaluate the
      cytological diagnosis and DNA ploidy analysis of 469 patients with previously
      diagnosed superficial transitional cell carcinoma. Cytological and DNA ploidy
      analysis was performed on 1,034 urine and bladder wash specimens, and the
      patients were monitored with cystoscopy and biopsies as clinically indicated.
      Cytology results were classified as normal, atypical, dysplastic or cancerous,
      and DNA ploidy was defined as normal if the diploid index was 1.2 or less, the S
      phase+G2M fraction was less than 21% or if there were 3% or less hyperploid
      cells, or abnormal if there was an increased S phase+G2M fraction, an aneuploid
      peak on the histogram or tetraploidy or hyperploidy was present. RESULTS: The
      majority of patients (85 of 88, 97%) with a cytological diagnosis of cancer had
      an abnormal DNA ploidy, and in 60 of 85 of these patients (71%) recurrence was
      diagnosed within 6 months. Only 5 of 284 specimens (2%) with normal cytology had
      abnormal DNA ploidy and 1 of these 5 (20%) heralded transitional cell carcinoma
      recurrence. However, in 145 patients with atypical cytological findings 29 (20%)
      with abnormal DNA ploidy had a recurrence, compared to 20 of 391 (5%) with normal
      DNA ploidy (p < 0.0001). Similarly, in 101 patients with dysplastic cytological
      findings 39 (39%) with abnormal DNA ploidy had transitional cell carcinoma
      recurrence compared to 4 of 25 with normal ploidy (p = 0.033). CONCLUSIONS:
      Abnormal DNA ploidy determined by image analysis significantly enhances the
      detection of bladder tumor recurrence in patients with atypical or dysplastic
      cytology but not in those with normal cytology or frank carcinoma on cytological
      findings.

PMID- 9258088
TI  - Palliative effect of intravesical bacillus Calmette-Guerin in elderly patients
      with advanced bladder carcinoma.
AB  - PURPOSE: Intravesical bacillus Calmette-Guerin (BCG) was used to palliate severe
      local symptoms in patients with invasive carcinoma. MATERIALS AND METHODS: Four
      patients with unresectable bladder carcinoma who were unfit for radical
      cystectomy because of age and poor performance status were treated with a 6-week
      course of BCG followed by monthly instillations. RESULTS: Urgency and frequency
      were reduced in 3 patients and the improvement lasted for 9 to 19 months. All 4
      patients ultimately died of bladder carcinoma. CONCLUSIONS: The results of
      palliative BCG treatment were encouraging, but further experience is necessary.

PMID- 9258089
TI  - Late urological complications and malignancies after curative radiotherapy for
      gynecological carcinomas: a retrospective analysis of 10,709 patients.
AB  - PURPOSE: A retrospective study was done to analyze late urological complications
      following curative radiotherapy of primary gynecological carcinomas. All patients
      were treated at a single center and with the same radiotherapeutic regimen. The
      incidence of other carcinomas in these patients was also evaluated. MATERIALS AND
      METHODS: A total of 10,709 patients was treated using combined telebrachytherapy
      (dosage 67.5 Gy.) during an observation period of 22 years. RESULTS: Severe late
      complications were seen in 1.24% (133 of 10,709) of the patients, including
      irradiated bladder (65 cases, mean interval since treatment 6.7 years).
      Complications required surgery in 118 of 133 patients with a perioperative
      mortality of 4.2% (5 of 118). Overall in 4.27% (457 of 10,709) of the patients
      another malignancy developed after (29.1%), during (26.3%) and before (44.6%)
      radiotherapy. Subsequent malignancies after treatment were predominantly seen in
      the genital region (88.4%) but they were also in the irradiated nongenital area
      (0.13%, 14 of 10,709). Of the latter patients 6 had urothelial bladder cancer,
      which represents a relative risk of 4.66 (based on the Austrian female
      population) to develop bladder cancer after radiotherapy for gynecological
      cancer. CONCLUSIONS: Late urological complications after radiotherapy of the
      pelvis are rare but severe. Surgical therapy of irradiated tissues has a higher
      complication rate compared to surgery on nonirradiated tissue.

PMID- 9258090
TI  - Adjuvant home urethral balloon dilation for the recalcitrant urethral stricture.
AB  - PURPOSE: We determined the efficacy of adjuvant home balloon self-dilation as an
      alternative to office dilation and to reduce the likelihood of recurrence in
      patients with recalcitrant urethral strictures. MATERIALS AND METHODS: A total of
      31 men participated in a urethral self-dilating protocol following phallic
      construction, urethroplasty or visual internal urethrotomy, or as conservative
      management in 2 nonoperative candidates. Uroflow data and subjective information
      obtained by blinded questionnaire were reviewed. RESULTS: The 31 patients were
      followed for a mean of 18.7 months (range 3 to 45) after initial balloon
      dilation, and 25 (81%) were available for followup interviews. Of the 25 patients
      24 (96%) found no difficulty in learning the technique and 21 (84%) thought they
      received adequate training with 1 office visit. Most patients noted improvement
      in voiding with balloon dilation, and peak uroflowmetry rates were preserved or
      improvement with long-term followup. Six patients (19%) complained of discomfort
      with balloon placement, 3 (10%) noticed minor bleeding with dilation and 4 (13%)
      had urinary tract infections during followup. Following visual internal
      urethrotomy, no stricture recurrences were noted in 9 patients. Strictures
      recurred in 2 of 13 (15%) urethroplasty patients following balloon dilation.
      After radial forearm free flap phallic construction, a technique known to have a
      high re-stricture rate, 5 of 7 patients (71%) had recurrent urethral stricture.
      CONCLUSIONS: Preliminary results indicate that adjuvant outpatient urethral self
      dilation following surgical correction of urethral strictures in patients at high
      risk for recurrence is inexpensive and safe, as well as a potentially effective
      option in reducing stricture recurrence and maintaining urethral patency.

PMID- 9258091
TI  - Continence mechanism of the isolated female urethra: an anatomical study of the
      intrapelvic somatic nerves.
AB  - PURPOSE: A neuroanatomical study was initiated to gain better insight into the
      continence mechanism of the isolated urethra in women. MATERIALS AND METHODS: We
      performed a detailed gross and histological neuroanatomical study to identify the
      intrapelvic somatic pathway from the sacral spinal cord to the female urethral
      sphincter. Gross anatomical dissection was performed in 5 formalin fixed female
      adult pelvises by tracing the autonomic nerves from the pelvic plexus and the
      spinal somatic nerves from S2-S4 to the urethral sphincter. Immunohistochemical
      staining of urethral step sections with a neuropeptide specific antibody was
      performed to demonstrate the course of the periurethral somatic nerves in
      relation to the vaginal wall. RESULTS: Our study demonstrated an intrapelvic
      somatic pathway derived from the S2, S3 and S4 sacral roots, distinct from the
      peripheral pudendal nerve, supplying the levator ani and the urethra. The somatic
      nerves travel beneath the endopelvic fascia in close relation to the inferior
      vascular pedicle of the bladder and are susceptible to injury during radical
      pelvic surgery. Mixed autonomic fibers from the pelvic plexus travel along the
      course of the ureter and are also intimately associated with the vascular pedicle
      of the bladder. Immunohistochemical staining of urethral step sections
      demonstrated that the periurethral nerves travel in close relation to the lateral
      and anterior vaginal wall. CONCLUSIONS: We believe that the identification of
      intrapelvic somatic pathways to the urethra provides a basis for developing
      surgical techniques to preserve urethral somatic innervation during radical
      pelvic surgery in women.

PMID- 9258092
TI  - Terminal nerve distribution to the urethra and bladder neck: considerations in
      the management of stress urinary incontinence.
AB  - PURPOSE: Recent reports have suggested an increased incidence of intrinsic
      sphincter dysfunction, most of which seems to appear following the failure of a
      previous, usually vaginal, surgical repair. Our studies attempt to define more
      precisely the neuroanatomical relationships that exist in the region of the
      bladder neck and proximal urethra, and between the urethra and anterior vaginal
      wall. MATERIALS AND METHODS: We dissected the pelves of adult female cadavers and
      step sectioned them at 4 mm. intervals. Several staining methods were used on
      each section to identify and document the position of the nerves and vascular
      structures between the vaginal wall and urethra. RESULTS: A rich plexus of blood
      vessels and nerves with ganglia is located between the vaginal wall, and the
      proximal urethra and bladder neck. The greatest concentrations of nerves are in
      the 4 o'clock and 8 o'clock positions but nerve fibers are identified throughout
      the loose areolar tissue planes through which vaginal surgery for stress urinary
      incontinence is often performed. CONCLUSIONS: When performing surgical procedures
      for the correction of stress urinary incontinence, the possibility that
      denervation and devascularization of the terminal urethra and bladder neck
      secondary to surgical dissection could contribute to the subsequent development
      of intrinsic sphincter dysfunction should be considered.

PMID- 9258093
TI  - Single dose imipramine reduces nocturnal urine output in patients with nocturnal
      enuresis and nocturnal polyuria.
AB  - PURPOSE: We investigated the effect of imipramine on nocturnal urine output in
      patients with nocturnal enuresis. MATERIALS AND METHODS: There were 15
      monosymptomatic enuretic patients 15 to 37 years and 8 control subjects 25 to 32
      years old. We measured nocturnal urine output, urine osmolality, creatinine
      clearance, osmolal clearance, free water clearance, excretion of solutes,
      fractional excretion of sodium, fractional excretion of potassium and plasma
      vasopressin with and without a single oral dose of imipramine (1 mg./kg. of body
      weight) taken at 8 p.m. RESULTS: Baseline studies showed significantly larger and
      less concentrated nocturnal urine among enuretics compared with controls. We
      observed a marked antidiuretic effect of imipramine in 6 enuretics with severe
      nocturnal polyuria. The imipramine induced decrease in urine output was
      accompanied by reduced osmolal clearance. Approximately a third of the observed
      decrease in solute excretion was attributed to lower excretion of sodium and
      potassium. The remaining two-thirds were most likely caused by an increased
      tubular reabsorption of urea, which may be secondary to a sympathomimetic effect
      of imipramine tubules, possibly because of altered adrenal medullary function
      with an increase in proximal tubular sodium and water reabsorption. The resultant
      lower tubular flow rate facilitates tubular reabsorption of urea in the distal
      part of the nephron. CONCLUSIONS: Imipramine has a vasopressin independent
      antidiuretic effect if nocturnal polyuria is present. The antidiuretic effect of
      imipramine can be attributed primarily to increased alpha-adrenergic stimulation
      in the proximal tubules with a secondary increased urea and water reabsorption
      more distally in the nephron.

PMID- 9258094
TI  - Hyperbaric oxygen therapy in the treatment of Fournier's disease in 11 male
      patients.
AB  - PURPOSE: Optimal tissue oxygenation, as obtained by hyperbaric oxygen therapy,
      potentiates or restores the host's bactericidal mechanisms and wound healing
      activity in patients afflicted by serious synergeic aerobic and anaerobic
      infections of the cutaneous and subcutaneous tissues. Furthermore, hyperbaric
      oxygen therapy has a direct toxic effect on anaerobic bacteria. We describe our
      experience with hyperbaric oxygen therapy in the treatment of 11 patients with
      Fournier's syndrome. MATERIALS AND METHODS: The average age of our patients was
      59.5 years; the most common predisponsing condition was diabetes. All patients
      were treated with antibiotic therapy and hyperbaric oxygen therapy (minimum 5 and
      maximum 24 cycles, consisting of 90 minutes 2.5 atmosphere absolute pressure).
      Furthermore, 6 of these patients underwent surgical debridement of the wounds and
      3 patients underwent delayed reconstructive surgery. RESULTS: The results we
      obtained with hyperbaric oxygen therapy as an adjunctive measure for the
      treatment of these infections were excellent; our mortality rate for Fournier's
      disease was 0. Moreover, no complications whatsoever were observed. Furthermore,
      the 3 patients who underwent delayed corrective surgery presented with well
      healed tissues and their operations were not complicated by infections or other
      pathological conditions. CONCLUSIONS: We believe that our findings, although
      limited in number, underline the excellent results that can be obtained with
      hyperbaric oxygen therapy as an adjunct treatment in Fournier's disease.

PMID- 9258095
TI  - Undescended testes in adults: clinical significance of resistive index values of
      the testicular artery measured by Doppler ultrasound as a predictor of testicular
      histology.
AB  - PURPOSE: We evaluated the clinical significance of arterial impedance as a
      predictor of testicular histology in adults with undescended (inguinal) testes.
      MATERIALS AND METHODS: We performed arterial impedance and testicular diameter
      measurements with the use of color Doppler ultrasonography on 22 adults with
      undescended testes. Arterial impedance of the contralateral descended testes
      served as controls. All patients later underwent inguinal orchiectomy and the
      testes were examined histologically. RESULTS: Of the 22 undescended testes, 7 had
      arterial impedance values below 0.50, and the other 15 had values equal to or
      above 0.50. All testes with arterial impedance values below 0.50 had histologic
      scores between 2 and 3, whereas the others had scores of 3 and 8. Arterial
      impedance values and testicular volumes in the contralateral testes were
      significantly higher than the undescended testes. Although some of the testes
      with arterial impedance values above 0.50 had histologic score 3, testes with
      arterial impedance values below 0.50 never exceeded score 3. Volume differences
      of the undescended testes were not statistically significant. CONCLUSIONS:
      Arterial impedance of an undescended testis may have a predictive value and
      provide more accurate information about its histology than the volume measurement
      itself.

PMID- 9258096
TI  - Gonadal function of patients treated with cisplatin based chemotherapy for germ
      cell cancer.
AB  - PURPOSE: The cure rate of patients with germ cell cancer of the testis has
      considerably improved since the introduction of cisplatin based chemotherapy.
      Because these patients are in their reproductive years and because some of them
      will be infertile after treatment, the effects of cytotoxic treatment on gonadal
      function are investigated by hormonal evaluations. MATERIALS AND METHODS: In a
      transversal trial, luteinizing hormone, follicle-stimulating hormone and
      testosterone were determined radioimmunologically in serum samples of 232
      patients with germ cell tumors after unilateral orchiectomy (patient age 18 to 64
      years) up to 153 months after chemotherapy. Additionally, 51 of these patients
      were investigated in a longitudinal trial before and up to 5 years after
      chemotherapy. All patients received at least 2 courses of different cisplatin
      based chemotherapy regimens: cisplatin/vinblastine/bleomycin,
      cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bleomycin,
      cisplatin/vinblastine/bleomycin/ifosfamide/etoposide. Additionally, 11 patients
      with germ cell tumors (age 22 to 38 years, stage I) were investigated within the
      first year after orchiectomy and retroperitoneal lymphadenectomy but without
      chemotherapy. RESULTS: In the transversal trial, 24 of 73 patients investigated
      during the first year after chemotherapy showed elevated luteinizing hormone
      concentrations, 5 had subnormal serum testosterone and 65 had elevated serum
      follicle-stimulating hormone, reflecting spermatogenesis deficits. In 28 patients
      studied longer than 8 years after chemotherapy (median followup 8.5 years, range
      8.0 to 12.6), luteinizing hormone increased after chemotherapy and 60 months
      after treatment, and follicle-stimulating hormone was elevated in 1 patient,
      follicle-stimulating hormone was increased in 18 and testosterone was subnormal
      in 1. Patients without chemotherapy treatment showed gonadotropin and
      testosterone within normal range and 3 patients had elevated serum follicle
      stimulating hormone. In the longitudinal study, mean serum luteinizing hormone
      plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating
      hormone (7.79 +/- 0.13 IU/l.) and testosterone (18.6 +/- 0.17 nmol./l.) were
      within the normal range before chemotherapy; serum follicle-stimulating hormone
      was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p < 0.001). Mean
      luteinizing hormone and testosterone levels were within the normal range, but 60
      months after therapy the testosterone-to-luteinizing hormone ratio was still
      lower than before treatment (p < 0.05). CONCLUSIONS: In patients with germ cell
      tumors, a compensated insufficiency of the function of the Leydig cells was still
      observed up to 60 months after chemotherapy. Of these patients 68% showed
      elevated follicle-stimulating hormone levels, which reflected a functional
      insufficiency of the Sertoli cells with impaired spermatogenesis. This study
      shows that impairment of germinative functions is more severe and protracted than
      the impairment of the endocrine functions.

PMID- 9258097
TI  - Tumor markers in hydrocele fluids of patients with benign and malignant scrotal
      diseases.
AB  - PURPOSE: We evaluated the presence of human chorionic gonadotropin (hCG), alpha
      fetoprotein (AFP) and a panel of other tumor markers in the compartment next to
      the tumor (that is, the malignant hydrocele fluid). MATERIALS AND METHODS: We
      measured hCG, AFP, neuron-specific enolase, carcinoembryonic antigen and
      cytokeratin-19 fragments in cubital vein sera and in hydrocele fluids of patients
      with testicular cancer. Results were compared with those obtained from hydrocele
      fluids of patients with benign disease. RESULTS: All tumor markers remained under
      the respective cutoff values in benign hydroceles. In patients with pure
      seminomas, hCG levels were elevated in 66% of hydroceles but only once in
      peripheral sera, whereas AFP remained low in both compartments. Furthermore, of
      11 cases of nonseminomatous germ cell tumor hydrocele fluids, 3 with negative
      peripheral tumor marker values had to be reclassified marker positive, of which 2
      showed elevated hCG levels and 1 had increased levels of AFP. Significant changes
      of neuron-specific enolase and carcinoembryonic antigen concentrations could not
      be observed. However, a cytokeratin-19 fragment measured by Cyfra 21-1 assay was
      elevated in 2 of 3 seminomatous and in 4 of 8 nonseminomatous hydroceles.
      CONCLUSIONS: These data give a new insight into the in vivo secretion pattern of
      testicular germ cell neoplasms, which demonstrates that the term "marker
      negative" should be restricted to selected cases of testicular cancer. Analysis
      of tumor markers in hydrocele fluids may be a helpful tool in patients with
      scrotal swelling if clinical and sonographic results remain uncertain.

PMID- 9258098
TI  - Transrectal prostate ultrasonography: variability of interpretation.
AB  - PURPOSE: The current study was designed to compare the interpretation of the
      individual performing transrectal ultrasound examination (operator) with
      experienced individuals who interpreted the examination with and without the
      availability of clinical data. Inter-observer and intra-observer variability was
      compared to determine the reproducibility and reliability of the study. MATERIALS
      AND METHODS: All patients undergoing radical prostatectomy for treatment of
      localized carcinoma of the prostate underwent a transrectal ultrasound
      examination before the procedure. The sonogram was interpreted by the operator
      and reviewers. The radical prostatectomy specimen was examined pathologically and
      the staging as determined by ultrasound was compared with the pathological
      findings. RESULTS: Ultrasound operator accuracy for extracapsular extension and
      seminal vesicle invasion was 0.70 and 0.74, respectively, compared with the
      accuracy of the reviewers, which ranged from 0.59 to 0.75 and 0.44 to 0.74 for
      extracapsular extension and seminal vesicle invasion, respectively. In general,
      blinded reviews were less accurate than unblinded reviews but this was only
      statistically significant for 2 reviewers. CONCLUSIONS: Although for most
      reviewers the addition of clinical data did not improve the accuracy of the
      interpretation, an advantage was noted for the operator, that is, the individual
      performing the examination. In general, the technical quality of the examination
      was related to the accuracy of the readings.

PMID- 9258100
TI  - Competing risks of mortality in prostate cancer.
AB  - PURPOSE: We have observed that in prostate cancer older age, black race, high
      stage and no treatment are independently associated with higher disease specific
      and overall mortality. Because disease nonspecific mortality was not examined one
      cannot reasonably infer that higher overall mortality is largely due to higher
      disease specific mortality. To understand better the interactions of independent
      prognostic variables with overall mortality we jointly evaluated their effects on
      type of death and time to death. MATERIALS AND METHODS: Using the prostate cancer
      patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology
      and End Results program, we performed competing risks analysis with multivariate
      accelerated failure time model to examine if the prognostic factors were
      associated with type of death and time to death. RESULTS: Older age, black race
      and no treatment were independently associated with higher relative risk of
      disease specific and nonspecific mortality. Localized stage was associated with
      lower and higher disease specific and nonspecific mortality than regional stage,
      respectively. The relative risks of disease specific and nonspecific mortality
      were significantly different from each other for all prognostic factors.
      CONCLUSIONS: To our knowledge, a competing risks analysis in prostate cancer has
      not been done previously. While all prognostic factors were associated with
      disease specific and nonspecific mortality, the relative contribution of disease
      specific and nonspecific mortality to overall mortality varied by prognostic
      factor, with some prognostic factors associated with relatively high disease
      specific mortality while others were associated with relatively high disease
      nonspecific mortality. The similarity of the associations of age, race and
      treatment with disease specific and nonspecific mortality suggests that they mark
      an unidentified factor(s) that affects patient health nonspecifically. Such a
      factor(s) may partly or completely explain the association of treatment with
      lower disease specific mortality.

PMID- 9258099
TI  - Prospective evaluation of prostate specific antigen density and systematic biopsy
      for detecting prostate cancer in Japanese patients with normal rectal
      examinations and intermediate prostate specific antigen levels.
AB  - PURPOSE: To improve the specificity of cancer detection in patients with normal
      digital rectal examination and intermediate prostate specific antigen (PSA)
      level, PSA density has been recommended, with biopsy based on a PSA density of
      0.15 or more. PSA density is reportedly higher in Japanese men than in white men,
      because of physiological differences between the 2 races. We prospectively
      evaluated PSA density as a discriminator of prostate cancer in Japanese men.
      MATERIALS AND METHODS: We evaluated prospectively 60 consecutive men with normal
      digital rectal examinations and serum PSA levels of 4.1 to 10.0 ng./ml. enrolled
      during a 17-month period. All patients underwent transrectal ultrasound guided
      sextant biopsies, regardless of calculated PSA density and transrectal ultrasound
      findings. Serum PSA levels were determined by IMx assay. RESULTS: Overall, 8 of
      60 men (13%) had prostate cancer. There was no significant difference in mean PSA
      between those with positive and those with negative biopsies, but the difference
      was significant in the mean PSA density (mean 0.24 and 0.15, respectively, p <
      0.01). Receiver operating characteristics curves for PSA and PSA density
      demonstrated superior benefit for PSA density in this patient population. A
      reference PSA density value of 0.19 was chosen because it showed the highest sum
      of sensitivity and specificity, which gave a sensitivity of 75%, a specificity of
      87%, a positive predictive value of 46% and a negative predictive value of 96%.
      CONCLUSIONS: The results suggest that PSA density improves the specificity of
      cancer detection in men with a normal digital rectal examination and an
      intermediate PSA level. Although further study with a larger patient population
      is needed to obtain a best-fit value, an optimal PSA density cutoff seems to be
      higher than that recommended in the literature from western countries. Because of
      possible racial differences in serum PSA and prostate volume, the role of PSA
      density in Asian men should be studied independently.

PMID- 9258101
TI  - Is heparin contraindicated in pelvic lymphadenectomy and radical prostatectomy?
AB  - PURPOSE: We initiated a prospective study to verify or refute the complications
      of lymphocele formation and excessive blood loss associated with heparin
      prophylaxis in pelvic lymphadenectomy and radical prostatectomy. MATERIALS AND
      METHODS: A prospective study was completed on 579 men undergoing pelvic
      lymphadenectomy usually in association with radical prostatectomy. Patients were
      assigned to group 1 (given preoperative and postoperative subcutaneous heparin)
      and group 2 (no heparin). All patients were evaluated 2 to 3 weeks after surgery
      with ultrasound for pelvic lymphocele. RESULTS: There was no statistically
      significant difference in the number or size of pelvic lymphoceles or blood loss
      in group 1 versus group 2. CONCLUSIONS: The use of heparin prophylaxis to prevent
      thromboembolic complications in conjunction with pelvic lymphadenectomy and
      radical prostatectomy is not associated with increased blood loss or increased
      rate of lymphocele formation.

PMID- 9258102
TI  - New 3-dimensional mapping device for cystoscopy.
AB  - PURPOSE: The crucial shortcoming of cystoscopy is that it does not measure the
      size of observed objects, and so we developed a new device that adds measurement
      capability to the cystoscope. MATERIALS AND METHODS: The device consists of 5
      arms linked to each other by freely bending joints. Before use 1 end of the arm
      is fixed to the examination table and the other end is linked to the eyepiece of
      the cystoscope. While linked to the arms, the cystoscope can move freely in any
      direction. Each joint carries an accurate sensor to measure its angle. The angle
      measurements are calculated collectively to obtain the 3-dimensional coordinates
      at the tip of the cystoscope. The tip of the cystoscope can be moved to the other
      side of the objects to be measured, which provides a pair of 3-dimensional
      coordinates, because the distance between them can be calculated. RESULTS: We
      could calculate the distance between the bladder neck and each ureteral orifice,
      and the angle of the bladder neck formed with the left and right orifices in
      clinical cases. By continuous measurement of the location of the bladder neck and
      the ureteral orifice, it was clearly demonstrated that the distance between them
      increased as the bladder filled. CONCLUSIONS: Our computer assisted, 3
      dimensional mapping device can replace unreliable cystoscopic assessment with
      more reliable numerical values. New diagnostic criteria based on the exact
      numerical values can be established with the use of this device.

PMID- 9258103
TI  - Female Stress Urinary Incontinence Clinical Guidelines Panel summary report on
      surgical management of female stress urinary incontinence. The American
      Urological Association.
AB  - PURPOSE: The American Urological Association convened the Female Stress Urinary
      Incontinence Clinical Guidelines Panel to analyze the literature regarding
      surgical procedures for treating stress urinary incontinence in the otherwise
      healthy female subject and to make practice recommendations based on the
      treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE
      data base for all articles through 1993 on surgical treatment of female stress
      urinary incontinence. Outcomes data were extracted from articles accepted after
      panel review. The data were then meta-analyzed to produce outcome estimates for
      alternative surgical procedures. RESULTS: The data indicate that after 48 months
      retropubic suspensions and slings appear to be more efficacious than transvaginal
      suspensions, and also more efficacious than anterior repairs. The literature
      suggests higher complication rates when synthetic materials are used for slings.
      CONCLUSIONS: The panel found sufficient acceptable long-term outcomes data
      (longer than 48 months) to conclude that surgical treatment of female stress
      urinary incontinence is effective, offering a long-term cure in a significant
      percentage of women. The evidence supports surgery as initial therapy and as a
      secondary form of therapy after failure of other treatments for stress urinary
      incontinence. Retropubic suspensions and slings are the most efficacious
      procedures for long-term success (based on cure/dry rates). However, in the
      panel's opinion retropubic suspensions and sling procedures are associated with
      slightly higher complication rates, including longer convalescence and
      postoperative voiding dysfunction.

PMID- 9258104
TI  - End stage renal disease and prophylactic intracavitary interferon.

PMID- 9258105
TI  - Granulomatous mass in a nonrefluxing renal unit after bacillus Calmette-Guerin
      therapy for bladder cancer.

PMID- 9258107
TI  - Acquired penoscrotal smooth muscle hamartoma.

PMID- 9258106
TI  - Spontaneous rupture of the bladder as a complication of total vaginal prolapse.

PMID- 9258108
TI  - Oncogenic osteomalacia associated with prostate cancer.

PMID- 9258109
TI  - Re: Insertion of double pigtail ureteral stent for the prevention of urological
      complications in renal transplantation: a prospective randomized study.

PMID- 9258110
TI  - Re: Modified Ingelman-Sundberg bladder denervation procedure for intractable urge
      incontinence.

PMID- 9258111
TI  - Re: Intracorporeal phenylephrine reduces thioridazine (mellaril) induced priapism
      in a child.

PMID- 9258112
TI  - Re: Applied anatomy of the cremasteric muscle and fascia.

PMID- 9258113
TI  - Re: Malignant cytological washings from radical prostatectomy specimens: a
      possible mechanism for local recurrence of prostate cancer following surgical
      treatment of organ confined disease.

PMID- 9258114
TI  - Long-term results of renal transplantation in children with the prune-belly
      syndrome.
AB  - PURPOSE: We assessed the long-term efficacy of renal transplantation in children
      with the prune-belly syndrome. MATERIALS AND METHODS: We retrospectively compared
      the outcomes of renal transplantation in 9 children with the prune-belly syndrome
      and 100 with malformative uropathy. RESULTS: Graft survival in the prune-belly
      syndrome and control groups was 50 and 72% at 5 years, and 50 and 47% at 10
      years, respectively (not statistically significant). No statistically significant
      increase in serum creatinine was noted at 10 years in children with the prune
      belly syndrome. Two patients with the prune-belly syndrome underwent internal
      urethrotomy after transplantation. All patients voided well and did not require
      intermittent catheterization. CONCLUSIONS: Renal transplantation in children with
      the prune-belly syndrome is not associated with a high rate of failure. However,
      these patients must be followed with regular urological evaluation since voiding
      efficiency may deteriorate.

PMID- 9258115
TI  - Renal transplantation into abnormal bladders.

PMID- 9258116
TI  - Anti-angiogenic treatment with linomide as adjuvant to surgical castration in
      experimental prostate cancer.
AB  - PURPOSE: Escape from "castration inhibition," be it surgical or chemically
      induced, is still the major problem in prostate cancer treatment. New agents that
      can be given as adjuvant therapy are needed. Linomide has demonstrated both anti
      tumor and anti-angiogenic activity with little toxicity in the Dunning R-3327 rat
      prostate tumor system. Therefore it was deemed essential to study the efficacy of
      this drug in the adjuvant situation. MATERIALS AND METHODS: Linomide, roquinimex,
      was administered 3 times a week i.p. alone or in conjunction with castration to
      rats bearing the Dunning R-3327 PAP rat prostate tumor and its effect on tumor
      growth analyzed. Similar experiments, in which Linomide 25 mg./kg./day was given
      in the drinking water were carried out in rats with the Dunning R-3327 G tumor.
      The effect of treatment on blood vessel density and blood flow in the tumor was
      also assessed using an image analysis system. RESULTS: Linomide, 2.5 & 40
      mg./kg., administered from the day after castration inhibited the regrowth of the
      Dunning R-3327 PAP tumors In addition, Linomide 40 mg./kg. administered after
      tumor regrowth occurred following castration(week 10) inhibited further tumor
      growth. Inhibition of tumor regrowth after castration was also found in the
      Dunning G tumor. When Linomide treatment was stopped regrowth of the tumors
      occurred, either in the same animal or on transplantation to new intact hosts,
      demonstrating that the tumor cells were still viable. Tumor blood vessel density
      was decreased both after castration and Linomide treatment alone, 40 and 32%
      respectively. On combination of castration and Linomide a 60% decrease in blood
      vessel density was found. This was significantly different from either of the two
      treatments given alone. The enhancement on combining castration and Linomide was
      confirmed by a further decrease in blood flow, from 19 and 22 to 12 ml. per
      minute/gm. tissue respectively. CONCLUSIONS: Linomide, an anti-angiogenic drug,
      inhibits escape from "castration inhibition".

PMID- 9258117
TI  - The significance of Ras guanine nucleotide exchange factor, son of sevenless
      protein, in renal cell carcinoma cell lines.
AB  - PURPOSE: The aim of the present study is to clarify the significance of the Ras
      guanine-nucleotide exchange reaction in the proliferation of human renal cell
      carcinoma cell lines. MATERIALS AND METHODS: We examined the expression of human
      son of sevenless-1 (hSos-1) protein and the epidermal growth factor (EGF)
      receptor in human renal cell carcinoma cell lines by Western blot analysis.
      Additionally, a dominant negative H-ras mutant, N116Y, which is known to inhibit
      the Ras guanine-nucleotide exchange reaction, was transfected into these cell
      lines by lipofection. RESULTS: Human renal cell carcinoma cell lines expressed
      much higher amounts of the EGF receptor and hSos-1 protein than normal kidney
      tissue. Moreover, the N116Y ras mutant could strongly suppress cellular
      proliferation in these cell lines. CONCLUSIONS: Augmentation of the Ras guanine
      nucleotide exchange reaction might be essential to the proliferation of human
      renal cell carcinoma cells.

PMID- 9258118
TI  - Intravesical therapy with vinorelbine tartrate: antitumor activity in orthotopic
      murine cell carcinoma of the bladder.
AB  - OBJECTIVES: To ascertain intravesical vinorelbine tartrate (VNR) antitumor
      activity against MB-49, a murine transitional cell carcinoma of the bladder
      (TCC), in an in vivo setting. MATERIALS AND METHODS: C57B1/6J female mice were
      intravesically implanted with 5 x 10(4) MB-49 cells and treated locally with VNR.
      Tumor incidence and volume analyses, as well as survival studies were carried
      out. RESULTS: Tumor incidence was significantly lower in VNR-treated mice (48%, n
      = 23) than in controls (84%, n = 19), as evaluated sixteen days after MB-49
      orthotopic inoculation. Intravesical tumor volume was also significantly smaller
      in treated mice respect to controls (median [range]: 0.5 [0.4 to 61.8] mm.3
      versus 47.7 [4.2 to 179.7] mm.3 respectively, p < 0.001 Kruskal-Wallis test).
      Median survival duration of the animals treated with VNR was 68 [21 to 68] days,
      and was significantly greater (p = 0.01, Kruskal-Wallis test) than that of
      untreated controls (18 [16 to 20] days). CONCLUSION: Intravesical VNR treatment
      demonstrated an evident antitumor effect against the TCC model assayed. The
      results obtained suggest a potential use of VNR as intravesical treatment for
      superficial TCC following transurethral bladder tumor resection to prevent
      recurrence or retard tumor growth.

PMID- 9258119
TI  - Effects of acute complete outlet obstruction on the NADPH-diaphorase reactivity
      in the intramural ganglia of the guinea pig urinary bladder: light and electron
      microscopic studies.
AB  - PURPOSE: The present study aims to examine the effect of complete outlet
      obstruction on the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH
      d) reactivity in the intramural ganglion cells of the guinea pig urinary bladder.
      MATERIALS AND METHODS: Adult male guinea pigs were divided into control (normal
      and sham-operated) and urethral obstructed (12, 24, and 48 hours after complete
      obstruction) groups. NADPH-d reactivity in the intramural neurons of the urinary
      bladder was examined by light and electron microscopy. RESULTS: At 12 hours after
      urethral obstruction, an increase in number of intensely stained NADPH-d
      intramural neurons was detected. This was sustained till 24 hours whence some of
      the neurons appeared to undergo degenerative changes. Neuronal degeneration was
      more drastic at 48 hours. Results of cell counts showed a 32% reduction in number
      of NADPH-d positive neurons of the urinary bladder at this time point. Electron
      microscopy showed that all neurons undergoing degeneration displayed NADPH-d
      reactivity. A large accumulation of NADPH-d reaction product was observed in
      degenerating neurons whose mitochondria appeared swollen along with dilatation of
      Golgi saccules. At 48 hours, some neurons displayed total vacuolation and lysis
      of mitochondria. CONCLUSION: Present results show that acute complete outlet
      obstruction can lead to degeneration and consequent cell death in the intramural
      ganglion cells of the guinea pig urinary bladder. The increased NADPH-d
      reactivity in such neurons suggests that nitric oxide may be involved in neuronal
      death in the urinary bladder following acute urinary retention.

PMID- 9258120
TI  - Effect of age and outlet resistance on rabbit urinary bladder emptying.
AB  - PURPOSE: To investigate the influence of age and effect of increased outlet
      resistance on the ability of rabbit bladders to empty in response to various
      methods of stimulation. MATERIALS AND METHODS: Bladders from six-month-old
      (young) and three-year-old rabbits (aged) were mounted in an in vitro whole organ
      bath system and filled with 15 ml. saline. The ability of the bladders to empty
      against low outlet resistance (LOR) and high outlet resistance (HOR) in response
      to field stimulation, bethanechol, and KCl was measured. The following parameters
      were measured: intravesical pressure and volume emptied. From these, flow rate,
      power, and external mechanical work were calculated. RESULTS: Maximum isometric
      pressure did not change with age. All bladders emptied with increased pressure
      and decreased flow rate at HOR. The young bladders generated a greater maximum
      power in response to bethanechol and KCl than the aged bladders at both outlet
      resistances, and maximum power did not change with increased resistance. The aged
      bladders did less work and emptied significantly less than the young bladders at
      the HOR. CONCLUSIONS: The aged rabbit bladders were unable to maintain the
      bladder contraction long enough to empty completely through an increased outlet
      resistance. Because maximum power remained constant when the outlet resistance
      was increased, it might be useful clinically to determine the emptying ability of
      the urinary bladder, independent of changes in outlet resistance. In addition,
      bladder work could be used to evaluate bladder function if the volume emptied is
      also taken into consideration.

PMID- 9258121
TI  - Inhibition of prostate ductal morphogenesis by retinoic acid.
AB  - PURPOSE: To examine the effect of retinoic acid on prostate ductal morphogenesis.
      MATERIALS AND METHODS: Newborn male Balb/C mice were injected with 25 mg./kg. all
      trans retinoic acid or vehicle alone. Animals were sacrificed at 60 days of age
      and prostate ductal morphology was quantitatively assessed by microdissection.
      Total prostate DNA was quantitated by DPA assay. RESULTS: The greatest effect was
      seen in the ventral prostate. Retinoic acid treated animals showed a 20% decrease
      in mean number of branch-points (p = 0.0006) with a corresponding 13% decrease in
      duct tips (p = 0.026). The combined ventral and dorsal prostate showed an effect
      with a 12% decrease in ductal branchpoints (p = 0.048). There was no effect on
      animal or organ weight and no effect on DNA content within the prostate. There
      was no difference in the prostate histology of treated and control animals.
      CONCLUSION: Retinoic acid administration in the newborn period inhibits mouse
      prostate ductal morphogenesis. This effect appears independent of an inhibition
      of overall growth.

PMID- 9258122
TI  - Analysis of fibronectin on human sperm.
AB  - PURPOSE: The purpose of this study was to localize fibronectin on human sperm and
      correlate its distribution with the morphological and functional integrity of
      sperm. MATERIALS AND METHODS: Semen samples were collected and sperm fractionated
      by swim-up. Subsets of the swim-up sperm were capacitated and acrosome reacted.
      Damage to swim-up sperm was induced by freezing and thawing. The presence of
      fibronectin on the surface of sperm was determined by immunocytochemistry.
      RESULTS: FN immunoreactivity was variable but staining on the sperm tail was
      consistently highest, whereas FN immunoreactivity over the acrosome and
      equatorial band was consistently lowest. Capacitation and acrosome reaction did
      not substantially change the distribution of FN staining. However, swim-up sperm
      had significantly less FN immunoreactivity (4%) than sperm that were unable to
      swim-up (12%; p < 0.01). Sperm that were deliberately damaged by freeze/thaw
      showed significantly increased FN binding (p < 0.01). FN immunoreactivity was
      inversely correlated with sperm viability (r = -0.68), motility (r = -0.70), and
      morphology (r = -0.63). CONCLUSIONS: This study demonstrates that only a minority
      of the sperm in an ejaculate stain positive for FN and the localization of FN in
      positive sperm is primarily to the tail. Inferior sperm stain more frequently for
      FN leading to an inverse correlation between FN staining and sperm quality. Taken
      together, these results do not support a role for FN in sperm-egg binding.
      However, FN staining may provide a method for selecting the highest quality sperm
      for use in assisted reproduction techniques.

PMID- 9258123
TI  - Effects of long-term oral administration of L-arginine on the rat erectile
      response.
AB  - PURPOSE: Nitric oxide (NO), the neurotransmitter responsible for mediating penile
      erection in the rat, is synthesized from L arginine by nitric oxide synthase
      (NOS) in a reaction blocked by L-NAME (N-omega-nitro-L-arginine methyl ester). To
      determine whether dietary supplementation of L-arginine can stimulate penile
      erection and whether ancillary pathways for penile erection may exist, a series
      of experiments were conducted in the Fischer 344 rat. MATERIALS AND METHODS:
      Adult male (5 month old) and aged (20 month old) rats were fed L-arginine (2.25%)
      and L-NAME (0.7%) dissolved in tap water for 8 weeks. Animals (n = 6) underwent
      electrical field stimulation (EFS) of the cavernosal nerve to induce erection and
      both maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP, mm.
      Hg +/- SEM) were measured. Tissue and serum levels of L-arginine were measured by
      an automated amino acid analyzer. Penile eNOS (endothelial) and nNOS (neuronal)
      content were measured by western blot densitometry. Total penile NOS enzyme
      activity was measured by the L-arginine to L-citrulline conversion assay.
      RESULTS: The L-arginine fed animals demonstrated a significant increase in EFS
      induced MIP when compared to the controls in both the adult (104 +/- 4 vs. 86 +/-
      6, p = 0.04) and aged (87 +/- 5 vs. 66 +/- 4, p = 0.02) animals, without changes
      in MAP. L-NAME virtually abolished the MIP in adult rats (8 +/- 3, p < 0.0001),
      while increasing the MAP (186 +/- 8, p < 0.0001). Serum and penile tissue levels
      of L-arginine were increased by 64-148% in all groups compared to control
      animals. Penile eNOS and nNOS content remained unchanged in control and treated
      animals. Penile NOS activity was increased nearly 100% in the L-arginine treated
      groups vs. controls. CONCLUSIONS: Long-term oral administration of supra
      physiologic doses of L-arginine improves the erectile response in the aging rat.
      We postulate that L-arginine in the penis may be a substrate-limiting factor for
      NOS activity and that L-arginine may up-regulate penile NOS activity but not its
      expression. The blockade of penile erection by EFS with L NAME suggests that if
      ancillary corporeal vasodilator mechanisms develop, a basal level of NO synthesis
      is still required for activation and relaxation of the corporeal smooth muscle.
      These data support the possible use of dietary supplements for treatment of
      erectile dysfunction.

PMID- 9258124
TI  - Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel
      target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas
      exotoxin.
AB  - We have discovered a new cell surface protein in the form of interleukin-13
      receptor on several solid tumor cells, including human renal cell carcinoma cells
      (Obiri et al., 1995; Debinski et al., 1995). This study reports that human
      prostate cancer cell lines also express high affinity IL-13 receptors (Kd = 159
      pM). These receptors are functional because IL-13 surprisingly increased
      proliferation of all three prostate cancer cell lines studied as determined by
      thymidine uptake and clonogenic assays. IL-13 receptors on prostate cancer cell
      lines were targeted using a chimeric protein composed of IL-13 and a mutated form
      of Pseudomonas exotoxin (PE38QQR). This molecule, termed IL13-PE38QQR, has been
      found cytotoxic to all three prostate cancer cell lines as determined by the
      inhibition of protein synthesis. The IC50 ranged between 1 nmol/l, to 15 nmol/l.
      These data were confirmed by clonogenic assays in which IL13-PE38QQR almost
      completely inhibited colony formation at 10 nmol/l. IL13-PE38QQR was not
      cytotoxic to cells that express little or no IL-13R. Heat inactivated IL13
      PE38QQR was not cytotoxic to prostate cancer cells indicating specificity. IL13
      PE38QQR was also cytotoxic to colonies when they were allowed to form first for
      several days before the addition of toxins. Our data suggest that additional
      studies should be performed to target IL-13 receptor bearing prostate cancer.

PMID- 9258125
TI  - Developmental expression of interstitial collagen genes in fetal bladders.
AB  - Bovine bladders at 3 stages during fetal development were examined for expression
      of collagens by immunohistochemistry as well as by measurement of steady state
      mRNA levels. Expression of type I and type III collagens during the fetal period
      was compared with that of adult cows as well as a young animal (heifer). Each
      bladder was separated into a detrusor and a urothelial-lamina propria sample
      which were then analyzed separately. Distribution and fiber arrangement of types
      I and III collagens were different depending upon the region of the bladder wall
      examined. Type III collagen, in particular, has a "coiled" appearance which is
      especially prominent within the lamina propria. Collagen gene expression showed a
      distinctive pattern which was different for both type I and type III collagen.
      While type I collagen gene expression peaked during the late second to early
      third trimester, type III collagen expression progressively decreased throughout
      the fetal period. In addition, expression of both collagens was greater in the
      urothelial-lamina propria fractions. These data demonstrate that the pattern of
      collagen gene expression in the developing bladder is developmentally regulated
      and is unique to each of the two major structural layers.

PMID- 9258126
TI  - Characterization of cocaine binding sites in the rat testes.
AB  - PURPOSE: An estimated 29 million individuals use cocaine in the United States.
      Studies have shown a high affinity for dose dependent binding of cocaine in the
      testes. Recent work done in our laboratory has shown that chronic administration
      of cocaine to male rats has an adverse effect on fertility and spermatogenesis by
      producing extensive morphological changes in the testes, leading to reduction in
      sperm production. As a first step toward understanding this process, we
      characterized and identified the pharmacological properties of [3H]cocaine
      binding sites in the testes. MATERIALS AND METHODS: Crude membranes from the
      testes were prepared from 35 days old male Sprague-Dawley rats. [3H]cocaine
      binding was measured by using the method of Madras et al. (1989) with
      modifications. The data from saturation binding assays were analyzed by Inplot
      (GraphPad Software, San Diego, CA) to determine the Kd and Bmax. RESULTS:
      Specific binding of [3H]cocaine was linearly dependent on membrane protein
      concentrations ranging from 0.2 to 8 mg./ml. The pooled data from three
      independent experiments revealed a mean affinity of 36 +/- 2.0 nM and Bmax of
      1.84 +/- 0.13 pmol/mg. The present study demonstrates that testicular tissue has
      receptor protein that binds [3H]cocaine saturably and specifically. Competition
      displacement experiments revealed a shallow displacement curve for (-)cocaine and
      Win 35,428 with r2 = 0.96, indicative of multiple binding components. Computer
      analysis confirmed that a two component binding model was preferred statistically
      over a one component model in all three experiments (p < 0.001). CONCLUSION: The
      results from these studies suggest that the testicular tissue contains a protein
      that binds [3H]cocaine in a saturable and specific manner. It has a different
      sensitivity from the [3H]cocaine binding protein in the brain and placenta.
      Further clarification of the relationship between cocaine and its recognition
      site is necessary to understand the mechanism of testicular damage after cocaine
      exposure.

PMID- 9258127
TI  - Treatment of ostial renal-artery stenoses with vascular endoprostheses after
      unsuccessful balloon angioplasty.

PMID- 9258128
TI  - Nitric oxide and interstitial cystitis.

PMID- 9258129
TI  - The management of unilateral poorly functioning kidneys in patients with
      posterior urethral valves.
AB  - PURPOSE: There is no uniform agreement on how to manage the unilateral
      nonfunctioning or poorly functioning kidney associated with posterior urethral
      valves. We studied the results of treatment of our patients to make
      recommendations regarding management of these kidneys. MATERIALS AND METHODS: We
      reviewed the records of 13 boys with a history of posterior urethral valves and a
      unilateral nonfunctioning or poorly functioning kidney, defined as less than 10%
      of total renal function on 99mtechnetium dimercapto-succinic acid renal scans.
      Variables investigated included pyelonephritis, hypertension, vesicoureteral
      reflux, nephroureterectomy, ureteral reimplantation and spontaneous cessation of
      reflux. We also evaluated how the management of abnormal urodynamic parameters
      influenced the results of reimplantation or medically induced cessation of
      reflux. RESULTS: Three of the 6 boys with grade 5 reflux ipsilateral to the
      poorly functioning kidney required nephroureterectomy at a mean age of 21 months
      because of recurrent urinary tract infections. Another 4 boys underwent
      successful ureteral reimplantation, including 2 who had bilateral grade 5 reflux,
      and 2 who had ipsilateral grade 4 reflux, and grade 3 (1) and grade 2 (1)
      contralateral reflux. Of 4 boys ipsilateral grade 3 reflux in 3 and bilateral
      grade 5 reflux in 1 disappeared without surgery after treatment of urodynamic
      abnormalities. Two patients with poorly functioning kidneys and no reflux did not
      undergo surgery. Overall 10 of the 13 poorly functioning renal units were not
      removed, and these patients were free of pyelonephritis and hypertension.
      Ureteral reimplantation (4 ipsilateral and 3 contralateral) was performed only
      after urodynamic abnormalities were addressed. All reimplantations were
      successful. CONCLUSIONS: Based on our results we believed that unilateral poorly
      functioning kidneys in patients with posterior urethral valves can be safely
      preserved in select patients without hypertension and pyelonephritis.
      Reimplantation to correct reflux may be preferable to nephroureterectomy in
      specific situations, such as when contralateral function is suboptimal and the
      contralateral ureter needs reimplantation. When indicated, reimplantation can be
      performed successfully if abnormal urodynamic parameters are addressed
      preoperatively. In fact, treating abnormal urodynamic findings may lead to
      spontaneous reflux resolution.

PMID- 9258130
TI  - Long-term renal function in the posterior urethral valves, unilateral reflux and
      renal dysplasia syndrome.
AB  - PURPOSE: The syndrome of posterior urethral valves, persistent unilateral reflux
      and renal dysplasia (VURD) is said to be protective of the contralateral
      nonrefluxing kidney and the outcome for renal function is reported to be
      excellent. We tested this hypothesis in our patients by replicating previous
      studies but with longer followup and glomerular filtration rate data. MATERIALS
      AND METHODS: We retrospectively reviewed the records of 183 boys presenting with
      posterior urethral valves between 1980 and 1989, including 12 who underwent
      nephrectomy for ipsilateral nonfunction and fulfilled all criteria for the VURD
      syndrome. Mean age at the most recent followup was 8.5 years. Serial serum
      creatinine levels and glomerular filtration rates were analyzed and compared to
      age matched normal values. RESULTS: Histological evaluation revealed dysplasia in
      all kidneys, confirming the VURD syndrome. Followup plasma creatinine was normal
      67% of the patients during year 2 of life, 50% between ages 4 and 5 years, and
      only 30% between ages 8 and 10 years. Glomerular filtration rate was within the
      normal range in 25% of boys tested in year 2 of life, and between ages 5 and 8
      years. CONCLUSIONS: Our data do not support the protective effect of the VURD
      syndrome on long-term renal function. All patients with posterior urethral valves
      require diligent long-term followup.

PMID- 9258131
TI  - Proximal urinary diversion in the management of posterior urethral valves: is it
      necessary?
AB  - PURPOSE: In infants with posterior urethral valves in whom renal function fails
      to normalize following decompression of the lower urinary tract supravesical
      urinary diversion is customarily recommended for presumed concomitant
      ureterovesical junction obstruction. We determined the true incidence of fixed or
      permanent ureterovesical junction obstruction and the renal prognosis for infants
      treated with proximal urinary diversion. MATERIALS AND METHODS: We evaluated 26
      patients with posterior urethral valves treated with supravesical urinary
      diversion. Mean gestational age at birth was 35 weeks (range 27 to 40). After
      initial decompression via an indwelling catheter for a median of 7 days (range 4
      to 18) persistently high serum creatinine was present (median 2.5 mg./dl., range
      1.9 to 3.5). One month after proximal urinary diversion median creatinine was 1.3
      mg./dl. (range 0.5 to 2.8). At 1 year, median nadir creatinine was 1.0 mg./dl.
      (range 0.3 to 2.5). At reconstruction a Whitaker test in all 26 patients (52
      renal units) demonstrated fixed ureterovesical junction obstruction in 2 units
      (4%). RESULTS: Renal biopsy in 44 of the 52 renal units (85%) revealed renal
      dysplasia. At a median followup of 9 years (range 1 to 14) end stage renal
      disease developed in 11 patients (42%). CONCLUSIONS: In neonates with posterior
      urethral valves who undergo proximal urinary diversion fixed ureterovesical
      junction obstruction is rare, renal biopsy invariably demonstrates areas of renal
      dysplasia and end stage renal disease frequently develops despite proximal
      diversion. These findings lead us to question the necessity of supravesical
      urinary diversion.

PMID- 9258132
TI  - Management of posterior urethral valves on the basis of urodynamic findings.
AB  - PURPOSE: Abnormal urodynamic findings are common in boys with a history of
      posterior urethral valves. However, to our knowledge there are few reports on the
      results of treating these abnormal findings. We analyzed the treatment of
      abnormal urodynamic parameters and its outcome in 21 boys who underwent valve
      ablation. MATERIALS AND METHODS: After valve ablation multichannel urodynamic
      studies were performed in 31 boys, including 21 in whom studies were done before
      and after therapy was started for abnormal parameters. Detrusor instability and
      impaired bladder compliance were treated with anticholinergics or augmentation
      cystoplasty, and impaired detrusor contractility was managed with clean
      intermittent catheterization. RESULTS: Before therapy 17 of 21 boys had impaired
      compliance and detrusor instability, 2 had impaired compliance without
      instability and 2 had instability alone. After treatment 8 boys had impaired
      compliance and 4 had detrusor instability. After anticholinergics were initiated
      new onset myogenic failure in 2 boys necessitated clean intermittent
      catheterization. Of the 13 patients who presented with urinary incontinence 10
      became dry and 3 had improvement with therapy. Vesicoureteral reflux in 10 boys
      at the time of the initial urodynamic study resolved in 7 with anticholinergic
      medication and in 1 after clean intermittent catheterization was begun for
      severely impaired compliance. All 21 boys were treated with anticholinergics and
      2 were ultimately treated with augmentation cystoplasty. Clean intermittent
      catheterization was also instituted in 5 patients, including the 2 who required
      clean intermittent catheterization after myogenic failure developed. Five boys
      with high voiding pressures were found to have outlet obstruction due to residual
      valve tissue in 2, bladder neck obstruction in 2 and urethral stricture in 1
      despite normal flow rates in 2. CONCLUSIONS: Urodynamic studies are helpful in
      guiding therapy in boys after valve ablation. Anticholinergic therapy can improve
      compliance, decrease detrusor instability, improve continence and eliminate
      vesicoureteral reflux in the majority of boys, although there is an associated
      risk of myogenic failure. Flow rates and fluoroscopic voiding studies are often
      unable to detect outlet obstruction and must be obtained in conjunction with
      voiding pressure measurements to make this diagnosis.

PMID- 9258133
TI  - Natural filling cystometry in small boys with posterior urethral valves: unstable
      valve bladders become stable during sleep.
AB  - PURPOSE: Our aim was to demonstrate the voiding pattern in small boys with
      posterior urethral valves during the day and night. MATERIALS AND METHODS: Long
      term natural filling and standard cystometry was performed in 16 boys 1.4 to 6
      years old (mean age 3.4) in whom posterior urethral valves were diagnosed in
      infancy. The boys were divided into 2 groups according to whether they had day
      incontinence. RESULTS: All boys had instability in the daytime but at night
      bladders were mainly stable. Voiding frequency during the day was high at a mean
      of 1.7 and 0.5 voidings per hour in the day incontinent and day continent groups,
      respectively, compared to 0.1 voiding per hour at night in both groups. Voiding
      detrusor pressure was higher and functional bladder capacity was lower during the
      day than at night in both groups. CONCLUSIONS: Natural filling cystometry
      revealed pronounced instability during the day and stable bladders at night. This
      difference between day and night is an important factor contributing to frequent
      small voidings during the day, dry nights and high bladder volume in the morning.

PMID- 9258134
TI  - Prenatally detected posterior urethral valves: qualitative assessment of second
      trimester scans and prediction of outcome.
AB  - PURPOSE: We attempted to determine if the degree of second trimester dilatation
      and/or other qualitative sonographic features of the fetal urinary tract are
      predictive of postnatal outcome in male neonates with posterior urethral valves.
      MATERIALS AND METHODS: We reviewed ultrasound reports and/or hard copy imaging in
      17 cases of posterior urethral valves initially detected on second trimester
      scans (median gestation 18 weeks, range 15 to 23.5). Ultrasound appearance was
      categorized according to the pattern and severity of dilatation, cystic change or
      echogenicity of the renal cortex and presence of oligohydramnios. Outcome was
      reviewed at a median followup of 5.7 years (range 4.4 to 10). RESULTS: Of the 17
      cases there was a poor outcome in 10, including death in 4 and chronic renal
      failure in 6. Seven patients were alive and well with normal renal function at
      followup. The prognosis in cases of moderate or severe upper tract dilatation was
      poor. Of the 9 patients with marked prenatal hydroureteronephrosis 8 (89%) were
      dead or had chronic renal failure at followup. In contrast, only 2 of the 8
      patients (25%) with mild upper tract dilatation or dilatation limited to the
      bladder had chronic renal failure at review (p = 0.05). Three cases of prenatal
      renal parenchymal change and 3 of subsequent oligohydramnios had a poor outcome
      postnatally. CONCLUSIONS: The prognosis for boys with prenatally detected
      posterior urethral valves is closely associated with qualitative aspects of
      second trimester scan findings. This information may be of clinical value in the
      prenatal counseling of parents.

PMID- 9258135
TI  - Increased renal echogenicity: a sonographic sign for differentiating between
      obstructive and nonobstructive etiologies of in utero bladder distension.
AB  - PURPOSE: The combination of in utero bladder distension and bilateral
      hydroureteronephrosis in male fetuses may result from a number of pathological
      processes. The prenatal and postnatal treatment of patients with an enlarged
      bladder is dictated by the specific etiology leading to these changes. We propose
      specific ultrasonographic criteria for differentiating between obstructive and
      nonobstructive etiologies in these fetuses. MATERIALS AND METHODS: We reviewed
      the medical records and prenatal imaging studies of 18 cases of marked in utero
      bladder distension in which a diagnosis of posterior urethral valves, the
      megacystis-megaureter association or the prune-belly syndrome was confirmed
      postnatally. Amniotic fluid volume and renal echogenicity were assessed before
      knowledge of the specific diagnosis. Oligohydramnios was graded as mild, moderate
      or severe. Increased renal echogenicity was defined as greater echogenicity of
      the renal cortex and/or medulla than of adjacent liver tissue. Postnatal imaging,
      clinical course and outcome were also reviewed. RESULTS: The study included 15
      cases with adequate followup, including 8 in which a diagnosis of posterior
      urethral valves was confirmed postnatally. Nonobstructive etiologies included the
      megacystis-megaureter association in 6 cases and the prune-belly syndrome in 1.
      Seven of the 8 patients with posterior urethral valves had moderate to severe
      oligohydramnios, whereas all but 1 with a nonobstructive etiology had normal
      amniotic fluid. Seven of the 8 cases with posterior urethral valves had a marked
      bilateral increase in renal echogenicity, while none of the nonobstructive cases
      had this finding. CONCLUSIONS: Increased renal echogenicity and oligohydramnios
      in the setting of bladder distension are highly predictive (87%) of an
      obstructive etiology. This finding is important in the prenatal counseling and
      treatment of boys with bilateral hydronephrosis and marked bladder dilatation.

PMID- 9258136
TI  - An algorithm for the management of anterior urethral valves.
AB  - PURPOSE: We present our management algorithm for patients with anterior urethral
      valves seen in the last 2 decades with and without the benefit of prenatal
      sonography. MATERIALS AND METHODS: A case series design was used to study 17
      cases of anterior urethral valves. Five patients presented with prenatal
      hydronephrosis from 1984 to 1993 and 12 presented with predominant voiding
      symptoms between 1975 and 1996 at a mean age of 6 years. RESULTS: Treatment
      included supravesical diversion in 1 case, vesicostomy in 5, urethroplasty in 5
      and transurethral fulguration in 6. Four of the 5 patients with a prenatal
      diagnosis of hydronephrosis had moderate to severe hydronephrosis compared to 3
      of the 12 who did not undergo prenatal sonography. All 17 patients were continent
      and infection-free, and had little or no hydronephrosis at a mean followup of 5
      years. CONCLUSIONS: We recommend vesicostomy in infants with high grade bilateral
      vesicoureteral reflux and poor emptying of the urinary tract, transurethral
      fulguration if the urethra has sufficient caliber and support, and urethroplasty
      in other patients. Based on our management algorithm patients with anterior
      urethral valves do not have sequelae due to distal obstruction of the urinary
      tract.

PMID- 9258137
TI  - Oral desmopressin: a randomized double-blind placebo controlled study of
      effectiveness in children with primary nocturnal enuresis.
AB  - PURPOSE: Desmopressin nasal spray has proved to be efficacious treatment of
      primary nocturnal enuresis. Oral desmopressin tablets would be a more easily
      used, convenient vehicle for our patients and their parents. We evaluated the
      effectiveness of oral desmopressin in decreasing the number of wet nights in
      patients with primary nocturnal enuresis. MATERIALS AND METHODS: We performed a
      double-blind, placebo controlled, parallel group trial of oral desmopressin in
      141 children 5 to 17 years old with documented primary nocturnal enuresis at 14
      sites. Patients were screened for number of wet nights for 2 weeks before study
      entry. A minimum of 3 wet nights weekly for 2 consecutive weeks was required for
      study entry. Patients were randomized to receive 200, 400 or 600 mcg.
      desmopressin or placebo before bedtime. Fluids were restricted 2 hours before
      bedtime based on body weight. The primary efficacy variable was mean decrease in
      the number of wet nights recorded during the last 2-week treatment period. The
      percentage of responding patients and mean decrease from baseline in number of
      wet nights at 2, 4 and 6 weeks were also assessed. RESULTS: The decrease in wet
      nights was 9, 20, 30 and 36% for placebo, and 200, 400, and 600 mcg. desmopressin
      orally per day, respectively. The 600 mcg. dose of oral desmopressin daily was
      statistically significantly different (p < 0.05) from placebo in decreasing wet
      nights. A complete or near complete response (0 to 2 wet nights) was noted in 3,
      18, 33 and 24% of the patients who received placebo, and 200, 400 and 600 mcg.
      oral desmopressin daily, respectively. The 400 and 600 mcg. treatment groups were
      statistically significantly different (p < 0.05) from placebo. A less than 50%
      decrease in wet nights was noted in 83, 79, 64 and 61% of the patients who
      received placebo, and 200, 400 and 600 mcg. oral desmopressin daily,
      respectively. Oral desmopressin exhibited a dose response in the treatment of
      primary nocturnal enuresis. The linear trend for the decrease in wet nights was
      statistically significant (p < 0.05). CONCLUSIONS: A dose of 600 mcg. oral
      desmopressin daily significantly decreased the mean number of wet nights when
      administered for 6 weeks. A higher dose may be necessary for an improved
      response.

PMID- 9258138
TI  - Bladder exstrophy: evaluation of factors leading to continence with spontaneous
      voiding after staged reconstruction.
AB  - PURPOSE: We performed a long-term retrospective review of patients with bladder
      exstrophy to evaluate the results of staged surgical reconstruction in regard to
      urinary continence, spontaneous voiding and preservation of the upper urinary
      tract. MATERIALS AND METHODS: We reviewed the charts of 42 boys and 15 girls
      treated at Hopital St. Joseph for bladder exstrophy between 1965 and 1995. All
      patients underwent staged repair, including bladder augmentation in 7 (12%) and
      secondary urinary diversion in 13 (23%). Criteria for good outcome in terms of
      continence are defined and factors influencing outcomes are reviewed. RESULTS: A
      total of 38 patients (67%) achieved good or acceptable urinary continence (22 or
      39% and 16 or 28%, respectively). Outcome was poor in 19 patients, including 13
      (23%) who underwent secondary urinary diversion. Bladder stones, which developed
      in 13 patients (23%), were the most common long-term complication of bladder
      exstrophy reconstruction. Ten patients who underwent pelvic osteotomies
      ultimately had better continence and 9 are dry. Bladder neck reconstruction was
      performed at a later age overall (mean 10 years). Repeat bladder neck
      reconstruction was generally associated with poor results. The technique of
      bladder neck reconstruction did not appear to influence outcome. CONCLUSIONS: A
      carefully planned surgical reconstruction for bladder exstrophy can lead to
      satisfactory long-term urinary continence in most patients. Factors contributing
      to successful results include early bladder closure, pelvic osteotomy, adequate
      bladder neck reconstruction with bladder neck suspension in girls, and a
      motivated child and family. Alternatives to surgical reconstruction should be
      discussed. Ultimate predictors of outcome in bladder exstrophy repair are
      difficult to ascertain.

PMID- 9258139
TI  - Detachable self-sealing membrane system for the endoscopic treatment of
      incontinence.
AB  - PURPOSE: The endoscopic treatment of urinary incontinence is limited by the
      injectable substances currently available. The ideal injectable material should
      be able to conserve its volume, be nonmigratory and nonantigenic. Toward this
      goal we developed a system for the treatment of incontinence in which a catheter
      with an inflatable and detachable self-sealing silicone membrane fits through a
      standard cystoscopic needle. We present our experience with this system.
      MATERIALS AND METHODS: A total of 20 female beagle dogs underwent cystoscopy and
      in 15 a self-sealing membrane was placed endoscopically in the submucosal region
      of the proximal urethra at the 3 and 9 o'clock positions. Each membrane was
      inflated through the delivery catheter with 0.2 cc povidone. Coaptation of the
      urethra due to the relative bulking effect of the inflated membrane was confirmed
      endoscopically in each animal. Five control animals received only an injection of
      saline. Four animals were sacrificed at 1, 3, 6, 12 and 18 months, respectively.
      At sacrifice gross and histological examinations were performed. RESULTS: At
      retrieval up to 18 months after implantation the membrane remained inflated and
      at the same position at which it had been initially placed. There was no evidence
      of povidone volume loss or extravasation. Membranes were encapsulated by a
      fibrous capsule. Only a few inflammatory cells surrounded the capsule by month 1
      and there were none by month 3. Histological examination of periurethral tissue
      and distant organs showed no evidence of particle migration. CONCLUSIONS: The
      detachable self-sealing membrane system is easily implantable, nonmigratory,
      nonantigenic and able to conserve its volume. These studies indicate that this
      system may be effective for the endoscopic treatment of incontinence.

PMID- 9258140
TI  - A simplified Kropp procedure for incontinence.
AB  - PURPOSE: A simplified Kropp bladder neck reconstruction was done to achieve
      urinary continence. MATERIALS AND METHODS: A total of 23 patients with an
      incompetent bladder neck underwent the procedure, including 22 with a neurogenic
      bladder secondary to myelodysplasia and 1 with bladder exstrophy. The bladder
      neck operation was incorporated into comprehensive lower tract reconstruction
      that included simultaneous augmentation cystoplasty in 20 patients,
      ureteroneocystostomy in 6 and appendicovesicostomy in 6. RESULTS: Of the 23
      patients 21 (91%) are continent. Complications included difficult catheterization
      in boys and new onset vesicoureteral reflux. CONCLUSIONS: This operation is
      easily performed and effective for achieving continence.

PMID- 9258141
TI  - Urethral lengthening and reimplantation: incidence and management of
      catheterization problems.
AB  - PURPOSE: Creation of a 1-way catheterizable valve has resulted in dryness for a
      large group of children with intractable urinary incontinence. We document the
      incidence, time course and management of catheterization problems in 49 children
      who underwent urethral lengthening and reimplantation for intractable
      incontinence. MATERIALS AND METHODS: We reviewed the records of 21 boys and 28
      girls who underwent urethral lengthening and reimplantation between 1982 and
      1995. Catheterization problems were defined as the inability of the patient or a
      family member to pass the catheter, and divided into early only, late only,
      recurrent and persistent problems. RESULTS: Of the 49 patients 46 had neurogenic
      incontinence secondary to myelomeningocele and 35 (72%) never had difficulty
      catheterizing. Of the 14 children (28%) who had difficulty 7 (50%) were boys and
      7 (50%) were girls. Two children (4%) with early only difficult catheterization
      have had no further difficulties during the last 14 and 6 years, respectively. In
      3 children (6%) late only difficult catheterization began 17, 24 and 35 months,
      respectively, after the original bladder neck surgery. These problems were solved
      by changing to a Coude catheter and/or avoiding over distension. The 7 patients
      (14%) with recurrent catheterization problems, some with long intervals between
      episodes, now catheterize easily. The 2 children (4%) with persistent problems
      required alternate access to the bladder. CONCLUSIONS: The majority of children
      (72%) who undergo urethral lengthening and reimplantation never have any
      difficulty catheterizing. Those in whom difficult catheterization develops can be
      treated with minimally invasive methods without compromising the goals of the
      original surgery.

PMID- 9258142
TI  - Development and regenerative ability of bladder in the transgenic epidermal
      growth factor receptor gene knockout mouse.
AB  - PURPOSE: During embryogenesis we have previously shown that urothelium is
      essential for normal bladder growth and development. Urothelial growth may be
      mediated by peptides of the epidermal growth factor family, since the epidermal
      growth factor receptor is expressed in bladder urothelium and epidermal growth
      factor has been shown to induce deoxyribonucleic acid synthesis and migration of
      urothelial cells in vitro. Bladders from transgenic mice in which the epidermal
      growth factor receptor gene has been knocked out were used to examine the
      possible role of epidermal growth factor in bladder growth and development,
      detrusor neoformation and bladder regeneration. MATERIALS AND METHODS: Whole
      bladders from transgenic knockout mice 0 to 10 days old were surgically implanted
      into the "subdetrusor" space of adult athymic nude rat hosts. After 10 days the
      dome of the host rat bladder was resected with the distal half of the
      transplanted knockout mouse bladder. Augmentation cystoplasty was then performed
      on the host rat bladder using acellular tissue matrix with a portion of the
      acellular matrix sutured directly to the transplanted knockout mouse bladder. The
      animals were sacrificed 2 or 3 weeks postoperatively. To test the ability of
      knockout bladder tissue to regenerate into the transplanted matrix species
      specific Hoechst dye was used to determine whether the cells within the acellular
      matrix were of host (rat) or transplant (knockout mouse) origin.
      Immunocytochemical analysis was used to assess muscle neoformation. Controls
      consisted of wild-type mouse bladders from the same litter. Since epidermal
      growth factor receptor knockout mice usually die in the neonatal period, the role
      of the epidermal growth factor receptor signaling pathway in long-term muscle
      development was evaluated by transplanting knockout and wild-type control
      bladders under the renal capsule of athymic nude mouse hosts. These mice were
      sacrificed 30 days later and muscle development was assessed using
      immunocytochemical analysis. RESULTS: Histologically the transplanted acellular
      tissue matrix in the experimental and control animals appeared the same,
      containing well differentiated urothelial and smooth muscle cells that had
      migrated into the transplanted matrix. Staining with species specific Hoechst dye
      revealed that urothelial and smooth muscle cells transplanted from the knockout
      and wild-type mouse bladders invaded and regenerated in the transplanted matrix.
      There was no apparent difference in the amount of knockout or control mouse
      tissue in the transplanted matrix. Also, the long-term renal capsule transplants
      revealed no difference in the amount of smooth muscle in the epidermal growth
      factor receptor knockout and wild-type bladders. CONCLUSIONS: Signaling through
      the epidermal growth factor receptor pathway is not necessary for normal bladder
      development or bladder regeneration after injury.

PMID- 9258143
TI  - A novel gene delivery system using urothelial tissue engineered neo-organs.
AB  - PURPOSE: Presently gene delivery is most effectively achieved by ex vivo gene
      transfer, which includes removal of the target tissue, in vitro gene delivery to
      the target cells, possible selection to enhance the proportion of transfected
      cells and reintroduction of the gene modified cells. Reintroduction of
      transformed cells in vivo has been a challenging task. Based on the feasibility
      of tissue engineering techniques in which cells seeded on biodegradable polymer
      scaffolds form tissue when implanted in vivo, we explored the possibility of
      developing a neo-organ system for in vivo gene therapy. MATERIALS AND METHODS:
      Normal human urothelial cells were harvested, expanded in vitro and seeded on
      biodegradable polymer scaffolds. The cell-polymer complex was then transfected
      with PGL3-luc, pCMV-luc and pCMV beta-gal promoter reporter gene constructs. The
      transfected cell-polymer scaffolds were then implanted in athymic mice and the
      engineered tissue was retrieved 0, 1, 3, 5 and 7 days after implantation.
      RESULTS: The reporter gene assay demonstrated an expression of luciferase
      activity at days 1, 3, 5 and 7 with the peak at day 5. X-gal and beta
      galactosidase antibody assays stained positive on the deoxyribonucleic acid
      treated transfection. CONCLUSIONS: Successful gene transfer can be achieved using
      biodegradable polymer scaffolds as a urothelial cell delivery vehicle. The
      transfected cell-polymer scaffold forms an organ-like structure with functional
      expression of the transfected genes. This study demonstrates that urothelial
      tissue engineered gene transfer is safe and effective.

PMID- 9258144
TI  - Partial bladder outlet obstruction in the fetal rabbit.
AB  - PURPOSE: We developed and tested an animal model of bladder dysfunction due to
      posterior urethral valves using partial outlet obstruction of the fetal rabbit
      bladder. MATERIALS AND METHODS: Partial bladder outlet obstruction of fetal
      rabbit bladders was created on day 23 of gestation. Of the litter of 8 to 10
      fetuses half was obstructed and the remainder served as controls. The doe and
      fetuses were sacrificed on day 30 of gestation (full term 31 to 32 days) and the
      fetal bladders were removed. Bladders that had doubled in weight from the average
      bladder weight of the control littermates were deemed sufficiently obstructed.
      Hematoxylin and eosin staining was performed and bladder strip response to 32 Hz.
      field stimulation, 200 microM. bethanechol and 200 mM. potassium chloride was
      measured. RESULTS: Average body weight did not differ between the control and
      obstructed fetuses, indicating that surgery did not hinder fetal development.
      Hematoxylin and eosin staining confirmed smooth muscle cell hypertrophy and
      increased connective tissue in the obstructed bladders. Obstructed bladder strips
      responded significantly less to field stimulation, and significantly more to
      bethanechol and potassium chloride (mean plus or minus standard deviation 5.18 +/
      1.52, 6.29 +/- 1.3 and 10.15 +/- 2.18 x force per/100 mg. tissue,
      respectively)than control bladder strips (9.0 +/- 1.19, 3.5 +/- 0.46 and 6.16 +/-
      1.33 x force per/100 mg. tissue, respectively) suggesting that denervation
      supersensitivity may have resulted from obstruction. CONCLUSIONS: Partial outlet
      obstruction of the fetal rabbit bladder results in bladder hypertrophy and
      dysfunction but these changes are markedly different from those in the adult
      rabbit. Since rabbit fetal development is delayed compared to human fetal
      development, this model can be used to assess the consequences of posterior
      urethral valves.

PMID- 9258145
TI  - Seromuscular colocystoplasty lined with urothelium protects dogs from acidosis
      during ammonium chloride loading.
AB  - PURPOSE: We compared the metabolism of intravesical ammonium chloride in dogs in
      which the bladder had been enlarged by seromuscular colocystoplasty lined with
      urothelium, dogs that had undergone conventional colocystoplasty and control
      dogs. MATERIALS AND METHODS: Eight adult female mongrel dogs were divided into
      control (2), colocystoplasty (3) and seromuscular colocystoplasty (3) groups.
      Serum creatinine, bicarbonate, sodium, chloride, and potassium levels were
      measured every 2 weeks during the 6-week recovery period. Six weeks after
      augmentation the dogs were placed under general anesthesia, the bladder was
      instilled with a hyperosmolar solution of 400 mmol/l. ammonium chloride, the
      femoral artery and portal vein were cannulated to obtain blood samples and the
      ureters were divided with the proximal ends diverted to allow serial urine
      measurements. Blood and urine electrolyte analysis was performed at 0, 60, 120,
      180 and 240 minutes after the intravesical instillation of ammonium chloride.
      RESULTS: During acid loading dogs that had undergone conventional colocystoplasty
      had a progressive decrease in serum carbon dioxide and arterial pH as well as
      increased levels of serum chloride and a significant increase in plasma ammonia
      concentration in the portal vein compared to controls and dogs that had undergone
      seromuscular colocystoplasty. In contrast, there were no differences in
      seromuscular colocystoplasty compared to control animals. CONCLUSIONS: Increased
      ammonia in the portal vein and hyperchloremic acidosis in dogs that underwent
      conventional colocystoplasty suggest intravesical absorption of ammonium
      chloride. Dogs that underwent augmentation with seromuscular colocystoplasty
      lined with urothelium seemed to respond to acute intravesical ammonium in a way
      similar to that of control dogs and they are protected from these metabolic
      anomalies.

PMID- 9258146
TI  - Methods to enhance in vivo urothelial growth on seromuscular colonic segments in
      the dog.
AB  - PURPOSE: We demonstrated survival and expansion in vivo of urothelial free
      autografts on demucosalized seromuscular segments. MATERIALS AND METHODS: Four
      methods of in vivo urothelial expansion were investigated on demucosalized
      colonic segments in the canine model. Group 1 underwent colonic mucosal removal
      by manual stripping, group 2 underwent removal of colonic mucosa and submucosa,
      and group 3 underwent manual stripping of the colonic mucosa followed by
      treatment with protamine sulfate and urea. In the 3 groups urothelial autografts
      were then placed on the seromuscular segment and tubularized over a balloon
      splint. In group 4 the colonic mucosa was removed but the grafts were not
      tubularized. Instead the colonic segment was sutured to the parietal peritoneum.
      RESULTS: Group 4 grafts had no epithelial growth and shrinkage of the bowel
      segment. Group 1 grafts had minimal growth with no expansion and colonic mucosal
      regrowth. Group 2 grafts demonstrated growth and expansion, although these
      colonic segments had a significant inflammatory response and fibrosis. Group 3
      grafts had the best growth and expansion with the least inflammatory response,
      and 1 colonic segment was almost completely covered with urothelium. CONCLUSIONS:
      We demonstrated in vivo expansion of urothelial autografts grown on seromuscular
      colonic segments. Preservation of the submucosa is essential to prevent fibrosis
      of the seromuscular colonic segment and a balloon stent is crucial to prevent
      graft contraction. Treatment of the demucosalized segment with protamine sulfate
      and urea results in better urothelial expansion and less colonic mucosal
      regrowth.

PMID- 9258147
TI  - The effect of Wilms tumor chemotherapy on contralateral renal growth after
      nephrectomy.
AB  - PURPOSE: Our aim was to evaluate the effect of current Wilms tumor chemotherapy
      on renal growth and function after unilateral nephrectomy. MATERIALS AND METHODS:
      Yorkshire piglets were enrolled in 2 study groups: group 1--6 underwent
      unilateral nephrectomy and placebo infusion, and group 2--10 underwent
      nephrectomy, and infusion of 7.5 mcg/kg. actinomycin D and 0.75 mcg/m2
      vincristine according to the National Wilms Tumor Study 4 protocol. Weekly
      measurements of renal size by ultrasound and gross specimens at sacrifice at age
      11 weeks were examined and weekly laboratory studies were recorded. Growth rates
      of renal length and volume were evaluated by linear regression analysis. Terminal
      renal length and volume were compared between groups. RESULTS: Mean slope plus or
      minus standard deviation of the rate of growth in length in the control and
      chemotherapy groups was 0.067 +/- 0.004 and 0.074 +/- 0.011, respectively (p < or
      = 0.148, not statistically significant). Mean slope of growth in volume was 1.401
      +/- 0.240 versus 1.642 +/- 0.456 (p < or = 0.252), average terminal renal length
      was 10.71 +/- 1.02 versus 11.58 +/- 1.03 cm (p < or = 0.13, not significant) and
      mean final volume was 128.67 +/- 32.41 versus 137 +/- 32.52 cc (p < or = 0.65).
      No differences in final serum creatinine levels were noted. CONCLUSIONS:
      Chemotherapy for Wilms tumor did not adversely affect contralateral renal growth
      or function in a nephrectomized piglet model.

PMID- 9258148
TI  - Hemodynamic changes after complete unilateral ureteral obstruction in the young
      lamb.
AB  - PURPOSE: We studied renal hemodynamic changes after complete acute unilateral
      ureteral obstruction in the young lamb. MATERIALS AND METHODS: Seven 4-week-old
      lambs underwent unilateral complete ureteral obstruction and renal blood flow was
      monitored in both kidneys with ultrasonic flow transducers. Ureteral and arterial
      blood pressure was measured. RESULTS: In the obstructed kidney renal blood flow
      was stable for 5 hours and then decreased thereafter to 71% of baseline at 5 days
      (p < 0.05). In the contralateral kidney the pattern of renal blood flow
      constituted a mirror image, although the magnitude of the increase was decreased
      (122% of baseline at 5 days, not statistically significant). Mean arterial blood
      pressure did not change in 5 days. Mean ureteral pressure increased from a
      baseline of 9 to 37 mm. Hg (p < 0.001) 2 hours after obstruction but gradually
      decreased to 24 mm. Hg after 24 hours and remained elevated for 5 days (p <
      0.001). CONCLUSIONS: The pattern of renal blood flow and ureteral pressure
      response to obstruction in the young lamb is different from that previously
      reported. Renal blood flow does not increase after obstruction and it is
      relatively preserved at 5 days. This unexpected response may be a result of the
      compound caliceal sheep kidney, immaturity of the young vascular system or
      development differences in the mechanism of spontaneous decompression of the
      collecting system.

PMID- 9258149
TI  - Active and passive compliance of the fetal bovine bladder.
AB  - PURPOSE: Others have shown that the fetal bovine bladder is relatively
      noncompliant. Previous studies on compliance of fetal bovine bladders have
      demonstrated that the youngest fetal bladders had lowest and the oldest fetal
      bladders (near full-term) had greatest compliance. Our study was designed to
      determine the level of participation of active tension in the compliance of fetal
      bladders during gestation. MATERIALS AND METHODS: Fetal bovine bladders were
      obtained immediately after maternal harvest and crown-to-rump length was measured
      to determine gestational age. The fetus was inspected for genitourinary anomalies
      and the bladder was immediately placed in chilled M199 media. Strips (1 x 0.5
      cm.) were excised from the anterior sagittal plane of the bladder and subjected
      to length-tension analysis in oxygenated Tyrode's buffer at 37C. Tension was
      measured using a force transducer and length was increased using a
      micropositioner. Compliance refers to the length-tension studies performed in
      normal Tyrode's solution and consists of a combination of active (smooth muscle
      tone) and passive properties. Passive compliance refers to length-tension studies
      performed after inactivation of bladder smooth muscle tone. Compliance with
      muscle tone intact was determined by incrementally stretching the strips to twice
      resting length in physiological buffer and then permitting them to return to
      resting length. Passive compliance with muscle tone ablated was determined in the
      same fashion after overnight incubation in calcium-free Tyrode's buffer in the
      presence of 5 mM. egtazic acid and 10 mM. sodium azide. An exponential function
      was fit to the normalized length-tension curves, where the exponential
      coefficient (EC) is numerically inversely proportional to compliance. RESULTS:
      Passive compliance was greatest in the youngest bladders (EC = 0.5 in the first
      trimester) and gradually decreased with increasing fetal age (EC = 1.2 in the
      third trimester). Active compliance demonstrated the opposite pattern, since the
      younger bladders were more stiff (EC = 2.1 in the first and 1.6 in the third
      trimesters). CONCLUSIONS: These studies demonstrate that passive compliance is
      greatest in the youngest bladders and progressively decreases with gestation.
      However, active smooth muscle tone is greatest in the youngest bladders and
      decreases with gestation. Thus, high active smooth muscle tone in the youngest
      fetal bladders results in relatively poor compliance of the early stage fetal
      bladder.

PMID- 9258150
TI  - The effect of angiotensin converting enzyme inhibition and angiotensin II
      receptor antagonism on obstructed rat bladder.
AB  - PURPOSE: Others have demonstrated that inhibition of angiotensin II production
      partially ameliorates obstructive changes in the neonatal rabbit bladder. We
      examined the effect of angiotensin II converting enzyme inhibition and receptor
      antagonism on the obstructed rat bladder. MATERIALS AND METHODS: Three groups of
      animals were investigated. Partial bladder neck obstruction was created in 23
      rats by placing a 2-zero silk ligature around the vesicourethral junction. Eight
      rats were given untreated tap water, 9 were given water supplemented with 50
      mg./kg. of the angiotensin-converting enzyme inhibitor captopril and 6 were given
      water with 30 mg./kg. of the angiotensin II subtype AT1 receptor antagonist
      losartan potassium. Eight unobstructed rats served as controls. After 2 weeks of
      partial outlet obstruction the animals were sacrificed and bladders were
      harvested. Routine histological evaluation and assays for total protein,
      deoxyribonucleic acid and collagen content were performed. RESULTS: Histological
      evaluation revealed that administration of captopril or losartan potassium
      resulted in a mild decrease in the degree of obstructive bladder changes.
      Biochemically neither captopril nor losartan potassium caused a significant
      decrease in the amount of total deoxyribonucleic acid, protein or collagen
      content per bladder compared to untreated obstructed bladders. CONCLUSIONS: In
      contrast to previous studies in neonatal rabbits, neither captopril nor losartan
      potassium significantly ameliorated the histological or biochemical features of
      partial bladder outlet obstruction in the rat. Further investigation is necessary
      into species specific differences to understand better the role that angiotensin
      II may have in mediating the bladder changes of experimentally induced
      obstruction.

PMID- 9258152
TI  - The effect of testosterone on androgen receptors and human penile growth.
AB  - PURPOSE: Recent rat studies suggest that early exposure to exogenous testosterone
      accelerates the loss of androgen receptors and compromises eventual penile
      length. In humans we hypothesize that down regulation of the androgen receptor is
      not the mechanism that stops penile growth. To test this hypothesis we
      investigated the effects of androgen deprivation and supplementation on the
      developing human penis. MATERIALS AND METHODS: A total of 15 normal human fetal
      penises at 7 to 19 weeks of gestation (mean plus or minus standard deviation 12
      +/- 4.5) was divided in half sagittally. Specimens were grafted beneath the renal
      capsule of male athymic nude mice or nude rats. Three groups of host animals were
      prepared, including 10 with no testosterone that were castrated at grafting, 15
      with testosterone and 5 with super testosterone in which 50 mg. testosterone
      propionate pellets were implanted subcutaneously at grafting. Each fetal penile
      specimen was its own control, since half was implanted into an intact animal and
      the other into a castrated or super testosterone host. Six weeks after grafting
      the specimens were analyzed for gross size (length), histology and expression of
      androgen receptors. RESULTS: All human fetal penile specimens grew from the nadir
      size and appeared as white exophytic growths on the surface of the host kidneys.
      Normal grafts were larger than castrate specimens (mean 6.9 +/- 2.1 versus 3.9 +/
      2.1 mm., p = 0.014). Mean length of the super testosterone specimens (7.3 +/-
      2.3 mm.) was not significantly greater than that of normal specimens (p = 0.797).
      Histological analysis revealed that all specimens were composed of viable penile
      tissue. Cellular density of the castrate penises was approximately 2 times
      greater than that of the normal and super testosterone specimens (40.6 +/- 5.9
      versus 25.1 +/- 2.8 cells per cm.2, p > 0.001), as calculated on enlarged
      micrographs. Supraphysiological doses of testosterone did not change the
      histology compared to controls. Immunohistochemical localization revealed
      androgen receptors expressed throughout the corporeal bodies, surrounding stroma
      and penile skin with intracellular localization to nucleus. The mean proportion
      of cells expressing androgen receptors was higher in the castrate (29.4 +/- 5.2
      cells per cm.2) than in the normal (24.0 +/- 3.7) and super testosterone (24.7 +/
      4.5) grafts (p = 0.005). However, in regard to growth there was no change in the
      proportion of androgen receptor positive cells among the groups. CONCLUSIONS:
      Testosterone influences penile growth, possibly as a result of extracellular
      stromal expansion. The number of androgen receptor positive cells in the human
      fetal penis did not change among the castrate, normal and super testosterone
      hosts. These experiments support the hypothesis that penile growth cessation is
      mediated by mechanisms other than down regulation of the androgen receptor.
      Furthermore, these data support the hypothesis that early administration of
      androgen to prepubertal male individuals does not result in a shorter phallus in
      adulthood.

PMID- 9258151
TI  - The ontogeny of canine small intestinal submucosa regenerated bladder.
AB  - PURPOSE: Small intestinal submucosa has previously been shown to promote
      regeneration of transitional epithelium, smooth muscle and peripheral nerves in
      rat and dog bladders. The origin of these regenerated components is presently
      unknown. This study attempts to define the origin of vascular, smooth muscle and
      peripheral nerve regeneration. MATERIALS AND METHODS: A total of 22 adult male
      dogs weighing 25 to 30 kg. underwent partial cystectomy and immediate
      augmentation with a small intestinal submucosa patch graft. The small intestinal
      submucosa graft-native bladder interface was marked with permanent marking
      sutures for future reference. Small intestinal submucosa regenerated bladders
      were harvested at 2, 3, 4, 6, 8 and 10 weeks after augmentation. The tissue was
      then studied with routine histology and immunohistochemistry using factor VIII,
      smooth muscle specific actin (1A4) and neurofilament staining. RESULTS: Results
      demonstrated that epithelialization of the graft surface was complete by 3 to 4
      weeks with normal transitional histology. In the early periods neovascularization
      was prominent throughout the entire graft, as shown by factor VIII staining.
      Later more mature vessels were noted. Early in muscle formation sheets of
      elongated spindle cells extended into the graft from the incised native bladder
      at both surgical margins and ran parallel to the mucosal surface. At 4 weeks this
      spindle cell proliferation completely traversed the graft. Trichrome stained
      sections of the 4-week-old grafts showed no evidence of muscle differentiation
      and the spindle cells appeared to be fibroblasts. However, these cells stained
      positive for smooth muscle specific actin (1A4), indicating myogenic potential.
      Between weeks 4 and 6 the spindle cells became more haphazardly arranged and were
      separated by loose interstitium. By weeks 8 to 10 there was distinct smooth
      muscle bundle formation within these areas of proliferating myocytes. Neural
      regeneration appeared to coincide with smooth muscle development. Early
      neurofilament positive cells were noted predominantly at the graft-native bladder
      interface. At 4 weeks neurofilament positive cells were present throughout the
      graft and by 10 weeks nerve trunks composed of several nerve fibers were
      identified in association with newly formed smooth muscle bundles. CONCLUSIONS:
      Small intestinal submucosa serves as a platform for bladder regeneration.
      Neovascularization smooth muscle and neural regeneration appear to occur through
      pannus ingrowth from the graft-native bladder interface. Smooth muscle
      regeneration seems to begin with the maturation of myofibroblasts, which migrate
      into the graft as early as 2 weeks after augmentation, and it progresses to the
      formation of distinct smooth muscle bundles by 10 weeks.

PMID- 9258153
TI  - Smooth and striated muscle development in the intrinsic urethral sphincter.
AB  - PURPOSE: The intrinsic urethral sphincter is composed of adjacent striated and
      smooth muscle. We studied the sequential expression of smooth and striated muscle
      proteins to gain insight into the ontogeny of intrinsic sphincter development.
      MATERIALS AND METHODS: The intrinsic urethral sphincters of timed Fischer 344 rat
      embryos at 14, 16 and 18 days of gestation, neonates on postnatal day 1 and adult
      animals were examined. Serial sections of the urethra and adjacent levator ani
      muscles were studied histologically with hematoxylin and eosin, anti-alpha-smooth
      muscle actin, anti-alpha-sarcomeric actin and antistriated muscle myosin heavy
      chain antibodies. RESULTS: The intrinsic urethral sphincter was identified within
      the periurethral mesenchyma as early as day 14 of gestation. Although striated
      myotubules were identified within the urethra by hematoxylin and eosin staining
      starting on postnatal day 1, striated muscle myosin heavy chain protein was
      absent in the embryonic and neonatal development of the sphincter, and it was
      expressed only in the mature myotubule of adults. alpha-Smooth muscle actin was
      expressed throughout the urethral sphincter of embryonic and neonatal animals. In
      adults alpha-smooth muscle actin was confined to the smooth muscle component of
      the urethra. Co-expression of alpha-smooth and alpha-sarcomeric muscle actin by
      the striated sphincter myotubule was noted only in neonates. CONCLUSIONS:
      Development of the intrinsic urethral sphincter is characterized by sequential
      expression of well characterized muscle marker proteins. The co-expression of
      smooth and striated muscle markers by developing sphincter myotubule suggests the
      possibility that trans-differentiation of smooth to striated muscle occurs in the
      developing genitourinary tract.

PMID- 9258154
TI  - Basic fibroblast growth factor in the urine of children with voiding pathology.
AB  - PURPOSE: Basic fibroblast growth factor is a mediator of tissue response to
      injury. Voiding pathology often results in bladder abnormalities. We
      prospectively determined whether basic fibroblast growth factor is elevated in
      the urine of children with bladder dysfunction compared to that of normal
      controls. MATERIALS AND METHODS: A total of 97 consecutive children with
      myelomeningocele and 32 with voiding pathology due to other etiologies underwent
      urodynamic testing, and 11 children with no bladder symptoms and sterile urine
      served as controls. Urinary basic fibroblast growth factor levels were assayed by
      enzyme-linked immunosorbent assay and normalized to urinary creatinine. RESULTS:
      Mean urinary basic fibroblast growth factor was higher in bladder dysfunction
      from myelomeningocele (6,673 pg./gm. creatinine, p = 0.0015) and other etiologies
      (5,665 pg./gm. creatinine, p = 0.0025) compared with urine from normal bladders
      (2,995 pg./gm. creatinine). In the myelomeningocele group urinary tract infection
      was associated with higher urinary basic fibroblast growth factor than in sterile
      urine (9,214 versus 5,642 pg./gm. creatinine, p = 0.018). Patient age, gender,
      remote bladder surgery, clean intermittent catheterization, detrusor
      hyperreflexia, detrusor compliance, age adjusted pressure specific bladder
      volume, low grade reflux and degree of trabeculation did not correlate with
      levels of basic fibroblast growth factor (p > 0.05). CONCLUSIONS: Urinary
      elevation of basic fibroblast growth factor, a critical mediator of wound repair,
      in children with voiding pathology and clinically abnormal bladders supports the
      paradigm that bladder dysfunction may result from generalized response-to-injury
      mechanisms. The role of fibrogenic cytokines, such as basic fibroblast growth
      factor, merits further directed investigation in bladder pathology.

PMID- 9258155
TI  - Repair versus observation in adolescent varicocele: a prospective study.
AB  - PURPOSE: We designed a randomized prospective study of male adolescents with
      moderate and severe varicoceles to determine whether prophylactic varicocele
      repair is beneficial. MATERIALS AND METHODS: We evaluated 2,100 boys (10 to 20
      years old) for genitourinary abnormalities. From this population 2 groups of
      adolescents 15 to 19 years old with grade 2 or 3 varicoceles were created,
      including 88 who underwent varicocele repair and 36 controls. Testicular volume
      and pampiniform vein diameter were measured, and Doppler ultrasound was
      performed. RESULTS: After 12 months volume of the involved left testis increased
      to almost normal in treated boys (mean atrophy index 12.7% at surgery and 3% 12
      months later). In controls the corresponding atrophy indexes were 10 and 9%,
      respectively. The relative increase in left testicular volume was 26% in the
      surgery group and 11% in controls. In the surgery group mean pampiniform vein
      diameter decreased from 2.8 preoperatively to 2 mm. postoperatively but there was
      no change in controls. CONCLUSIONS: Varicocele repair in adolescents with
      moderate and severe varicocele reversed testicular growth arrest and resulted in
      catch-up growth within 12 month of surgery.

PMID- 9258156
TI  - Stone formation after augmentation cystoplasty: the role of intestinal mucus.
AB  - PURPOSE: We evaluated the role of mucus in urine after bladder augmentation and
      hypothesize that mucus acts as a possible etiological factor in stone formation.
      MATERIALS AND METHODS: Mucus was collected via centrifugation from the 24-hour
      urine specimens of 8 stone forming and 10 nonstone forming patients who were
      randomly selected from our augmentation population. The mucus and stones were
      lyophilized, and then analyzed via scanning electron microscopy and energy
      dispersive x-ray spectrometry for calcium, phosphate, magnesium and sodium. The
      24-hour urine collections were also analyzed to determine any metabolic
      differences between the 2 groups. RESULTS: Scanning electron microscopy and
      energy dispersive x-ray spectrometry spectra showed increased calcium, phosphate,
      and magnesium, and significantly higher (p < 0.05) calcium-to-phosphate ratios in
      the mucus of stone versus nonstone forming patients. Of the 8 stones examined all
      had viscous fluid (mucus) centers rich in calcium, phosphate and magnesium.
      Calcium-to-phosphate ratios in the corresponding mucus recovered from stone
      centers were similarly high. Urinary citrate levels were low in both groups, and
      calcium, phosphate and magnesium were within normal ranges. CONCLUSIONS: Mucus
      appears to have an important role in the genesis of bladder stones after
      augmentation, possibly acting as a nidus. Metabolic changes following
      augmentation were similar in stone and nonstone forming populations. Our data
      suggest that mucous calcium-to-phosphate ratios may be predictive of future stone
      formation. Furthermore, there may be a benefit in instituting more aggressive
      measures aimed at clearing mucus from the bladder.

PMID- 9258157
TI  - Comparison of blood flow and histological changes in rat models of testicular
      ischemia.
AB  - PURPOSE: Our aim was to quantify objectively the degree of vascular insufficiency
      produced by twisting versus clamping the spermatic cord, and determine the
      contribution of the vasal vessels to these changes using the laser Doppler
      flowmeter. MATERIALS AND METHODS: Three groups of 12 male Sprague-Dawley rats
      each were studied. Group 1 underwent 720-degree torsion of the spermatic cord,
      group 2 underwent vascular clamping of the spermatic cord with 1 clamp, excluding
      the anatomically separate vasal vessels, and group 3 underwent vascular clamping
      of the entire spermatic cord and vasal vessels with 2 clamps. Blood flow and
      histological changes were determined. RESULTS: Vascular clamping of the spermatic
      cord in groups 2 and 3 resulted in a significant decrease in testicular blood
      flow compared to 720-degree torsion (p < 0.05). These flow changes correlated
      with more severe and reproducible gross changes, and histological features of
      seminiferous tubule degeneration compared to spermatic cord twisting.
      CONCLUSIONS: In the rat clamping the spermatic cord is a more severe and
      reproducible model of testicular torsion than 720-degree torsion. The
      contribution of the vasal vessels to the decrease in blood flow and resulting
      histological degeneration after testicular ischemia is negligible in the rat.

PMID- 9258158
TI  - Enteric mucosal regrowth after bladder augmentation using demucosalized gut
      segments.
AB  - PURPOSE: Regrowth of the enteric mucosa on a denuded muscular flap
      enterocystoplasty is an undesirable complication of demucosalized
      enterocystoplasty. This study was performed to understand how regrowth can be
      prevented and, thus, a complete urothelial lined enterocystoplasty can be
      achieved. MATERIALS AND METHODS: We performed bladder augmentation on 30 sheep
      using demucosalized seromuscular gastric or colonic flaps with or without
      autoaugmentation. The epithelium and muscularis mucosae were completely removed
      from the gastric flap. Initial attempts to remove the muscularis mucosae and most
      of the submucosal layer from the colonic flap by cautery caused bleeding and
      muscle damage. Thus, demuscosalization was done by stripping with forceps, in
      which the muscularis mucosae and submucosa remained largely intact on the colonic
      flap. Sheep were sacrificed 4 to 12 months postoperatively and bladders were
      inspected for mucosal regrowth. Subsequently autoaugmentation with demucosalized
      seromuscular gastric or colonic flaps was performed clinically in 10 children in
      whom the enteric epithelium and muscularis mucosae were removed completely with
      part of the submucosa by dissection through the submucosal plane. These children
      were followed with urodynamic studies and mucin staining of urine up to 39 months
      postoperatively. RESULTS: Regrowth of islands of enteric mucosa occurred in 4 of
      the 5 animals in which the muscularis mucosae and submucosal layers were
      preserved on a colonic flap. In all animals with mucosal regrowth the bowel was
      prepared by stripping the mucosa. Mucosal regrowth did not occur in any animal
      after complete removal of the muscularis mucosae and the inner portion of the
      submucosa from the stomach or colon. All patients had satisfactory urodynamic
      results and no evidence of enteric mucosal regrowth. CONCLUSIONS: Removal of the
      muscularis mucosae with the inner portion of the submucosa appears necessary to
      prevent enteric mucosal regrowth on the muscular flap of a demucosalized
      enterocystoplasty. In addition, this level of dissection does not seem to
      interfere with the success of bladder augmentation in children.

PMID- 9258159
TI  - Reconstitution of human urothelium from monolayer cultures.
AB  - PURPOSE: We established a 3-dimensional organ culture model of urinary tract
      tissue in which to study the effects of seeding cultured urothelial cells onto de
      epithelialized urothelial stroma. MATERIALS AND METHODS: Normal human urinary
      tract tissues were placed in organ culture or used to establish urothelial cell
      cultures. At passage 2 cell cultures were harvested and used to reconstitute
      autologous organ cultures by seeding onto de-epithelialized stroma. Organ
      cultures were harvested at intervals and analyzed by immunohistology with a panel
      of antibodies against differentiation associated antigens, cytokeratins, cell
      adhesion molecules, extracellular matrix components and proliferation associated
      antigens. RESULTS: Human urothelial tissues were maintained in organ culture for
      at least 18 weeks and they retained a transitional epithelial morphology with
      expression of normal in situ antigenic characteristics. Within 2 weeks of
      reconstitution recombined organ cultures formed a stratified, polarized,
      transitional-like neo-epithelium that expressed many of the phenotypic and
      differentiated characteristics of normal tissue. Basement membrane formed at
      sites of direct contact between urothelial cells and stroma. After an initial
      stabilization period the proliferation rate of the urothelium of intact and
      reconstituted organ cultures decreased to the low turnover rate characteristic of
      normal urothelium in situ, indicating that the cells were responsive to normal
      growth regulatory controls. CONCLUSIONS: Normal human urothelial cells, which
      express a proliferative nondifferentiated phenotype in monolayer culture, retain
      the capacity to differentiate and reform a slow turnover, stratified transitional
      epithelium.

PMID- 9258160
TI  - Pediatric Urology Medal. Panayotis P. Kelalis.

PMID- 9258162
TI  - Bulbar elongation anastomotic meatoplasty (BEAM) for subterminal and hypospadiac
      urethroplasty.
AB  - PURPOSE: All urethral reconstruction that involves substitution has an inherent
      ongoing incidence of restenosis with time. Anastomotic restoration of urethral
      continuity naturally obviates these complications but to achieve its potential of
      a long-term stricture-free success rate that approaches 100% circumstances must
      be ideal and the reconstructive surgical technique must be meticulous. If the
      critical indications for anastomotic reconstruction are overextended,
      complications inevitably increase. Considerable additional urethral length is
      required to overcome the terminal atretic deficiency associated with hypospadias
      and create a tension-free anastomotic neomeatoplasty. Mobilization and
      advancement of the penile urethra alone are rarely sufficient to achieve this
      without causing penile chordee. We describe the details of bulbar elongation
      anastomotic meatoplasty (BEAM) that we have been using for approximately the last
      8 years. MATERIALS AND METHODS: The only part of the urethra that can be
      mobilized to provide extra length for anastomotic urethroplasty without creating
      penile curvature chordee is the bulbar urethra. Full length mobilization of the
      whole length of the bulbar urethra through a perineal incision provides 2 to 2.5
      cm. of tension-free lengthening in children and 4 to 5 cm. in adults. Thus, many
      subterminal urethral deficiencies can be resolved by bulbar elongation
      anastomotic meatoplasty when the total extent of the urethral deficiency is not
      disproportionally long. We performed bulbar elongation anastomotic meatoplasty in
      12 patients 2 to 25 years old. RESULTS: At a followup of 2 to 7 years the
      neomeatus is functionally and cosmetically satisfactory in all cases with no long
      term complications or chordee. CONCLUSIONS: When circumstances are appropriate,
      bulbar elongation anastomotic meatoplasty is a preferable alternative to some of
      the current substitution procedures. Once established, anastomotic
      reconstructions are generally stable in the long term.

PMID- 9258163
TI  - Long-term results of distal urethral advancement glanuloplasty for distal
      hypospadias.
AB  - PURPOSE: In 1987 we developed distal urethral advancement and glanuloplasty, a
      surgical technique specifically intended for coronal and subcoronal hypospadias
      repair that involves moving the distal urethra 0.5 to 1 cm., Y shaped meatoplasty
      and glanuloplasty. MATERIALS AND METHODS: From January 1987 to December 1992, 271
      boys 9 months to 14 years old (mean age 2.5 years) underwent repair of distal
      coronal and subcoronal hypospadias, including distal urethral advancement and
      glanuloplasty in 135 (49.8%). RESULTS: Long-term results in 118 cases were
      determined at 4 to 9 years of followup (mean 6.3). In 112 cases (95%) good
      functional and cosmetic results were achieved, while in 6 (5%) complications
      required surgical repair, including meatal stenosis in 3 (2.5%), fistulas in 2
      (1.7%) and complete glanuloplasty disruption in 1. We evaluated outcomes in 19
      postpubertal patients 15 to 20 years old and noted no psychological or sexual
      problems as a consequence of hypospadias repair. CONCLUSIONS: Long-term followup
      confirms the validity of distal urethral advancement and glanuloplasty for
      correcting a large number of coronal and subcoronal hypospadias cases.

PMID- 9258161
TI  - Penile block timing for postoperative analgesia of hypospadias repair in
      children.
AB  - PURPOSE: It has been well established that a dorsal penile nerve block
      immediately after surgery decreases postoperative pain in children undergoing
      hypospadias repair. However, to our knowledge the efficacy of a penile block
      immediately before versus immediately after surgery for postoperative pain
      control has not been previously studied in such children. MATERIALS AND METHODS:
      We evaluated 98 healthy boys 6 months to 12 years old undergoing hypospadias
      repair. General anesthesia was induced and maintained in a standard fashion.
      Patients were randomly assigned to receive a penile block with the same total
      dose of bupivacaine at the completion of surgery, before the incision or before
      and at the completion of surgery. No other analgesic was administered
      intraoperatively. Pain was assessed using a modified objective pain-discomfort
      scale at 15 minutes, and 3, 12 and 24 hours after surgery. The number of doses of
      acetaminophen required to control postoperative pain was also recorded. RESULTS:
      Pain scores were defined in a range of 0-no pain to 6-greatest pain. During
      recovery median pain scores in the 30, 36 and 32 boys who received a penile block
      after, before, and before and after surgery were 3, 1.5 and 0 at 15 minutes; 2.5,
      1 and 0 at 3 hours; 3, 2 and 0 at 12 hours; and 1, 0 and 0 at 24 hours,
      respectively. There was no difference in acetaminophen doses required 15 minutes
      and 3 hours postoperatively in the 3 groups. By 12 hours after surgery the number
      of acetaminophen doses required for pain control was significantly lower in the
      before and after, and before groups than in the after group. By 24 hours boys in
      the before and after group required significantly fewer doses of analgesics than
      those in the after and before groups. There was no statistically significant
      difference between the after and before groups. CONCLUSIONS: Two penile blocks
      performed at the beginning and conclusion of hypospadias repair, respectively,
      provide better postoperative pain control than 1 penile block done before or
      after surgery (p < 0.05). These patients require less analgesic than those who
      receive a penile block only before or only after surgery.

PMID- 9258164
TI  - Comparison of onlay and tubularized island flaps of inner preputial skin for the
      repair of proximal hypospadias.
AB  - PURPOSE: Transverse island flaps of inner preputial skin have provided a reliable
      technique for the repair of proximal hypospadias. The flap may be used to create
      a neourethra by tubularizing the flap after urethral transection or applying the
      flap as an onlay patch onto an intact urethral plate. We retrospectively analyzed
      our experience with these 2 techniques to compare outcomes. MATERIALS AND
      METHODS: During 11 years 132 patients underwent hypospadias repair by a single
      surgeon using an onlay (58) or tubularized (74) island flap technique. Surgical
      results were reviewed retrospectively. RESULTS: At a mean followup of 20.3 months
      the overall complication rate was 36% for tubularized and 31% for onlay repair,
      and fistula rates were 14 and 17%, respectively. Despite similar fistula rates
      tubularized repairs tended to have larger fistulas that required more complex
      repair (p = 0.0147). In 9 patients who underwent tubularize repair diverticula
      developed, whereas no diverticula developed after onlay repair (p = 0.0162). The
      rates of urethral stricture, wound infection, residual chordee and cosmetic
      complications were not statistically significantly different between repairs. The
      use of double faced repair in 30 patients provided no difference in outcome in
      comparison to the overall study cohort. CONCLUSIONS: Hypospadias repair using
      transverse island flaps offers reliable and durable outcomes. While overall
      complication rates were not greatly different between tubularized and onlay flap
      repairs, onlay repair tended to result in fistulas of smaller size and
      diverticula did not develop.

PMID- 9258165
TI  - Nephrogenic adenoma after urethral reconstruction using bladder mucosa: report of
      6 cases and review of the literature.
AB  - PURPOSE: To our knowledge nephrogenic adenoma, an unusual benign metaplastic
      lesion of the urothelium, has not been reported previously following urethral
      reconstruction using bladder mucosa. Histopathological features, etiological
      factors and clinical features are discussed. MATERIALS AND METHODS: We reviewed
      the records of 117 patients who underwent hypospadias repair with free grafts of
      bladder mucosa from 1982 to 1995. RESULTS: Five children 6 to 11 years old and a
      39-year-old man had nephrogenic adenoma of the urethra. Hematuria or dysuria was
      the usual reason for presentation. The lesions were located at the site of
      anastomosis between the graft and proximal urethra in 3 cases and the distal
      graft in 2, and they involved the whole graft in 1. Successful treatment
      consisted of endoscopic resection of the polyps in 4 patients, while open
      surgical correction was performed in 2, requiring complete excision of the
      previous graft in 1 and segmental resection in 1. CONCLUSIONS: The gross
      appearance of the lesion may be confused with that of transitional cell carcinoma
      or clear cell adenocarcinoma of the urethra, necessitating biopsy to rule out
      malignancy. Endoscopic management is possible for small tumors, although severe
      nephrogenic adenoma involving most of the reconstructed urethra may require
      complete resection of the graft and creation of a new urethra.

PMID- 9258166
TI  - Stent-free Thiersch-Duplay hypospadias repair with the Snodgrass modification.
AB  - PURPOSE: Incision of the glanular urethral plate (the Snodgrass modification)
      permits tubularization of the neourethra in the Thiersch-Duplay fashion when
      anatomy would otherwise preclude a tension-free anastomosis and necessitate
      another operative technique for hypospadias repair. To take advantage of these
      cosmetic benefits without the potential morbidity associated with indwelling
      catheters, we performed a stent-free Thiersch-Duplay repair incorporating the
      Snodgrass modification. MATERIALS AND METHODS: The Thiersch-Duplay hypospadias
      repair was combined with the Snodgrass modification. Hinging the urethral plate
      was necessary when the glanular groove was too shallow to perform a standard
      Thiersch-Duplay repair. RESULTS: Stent-free repairs were performed in 33 children
      0.47 to 2.66 years old (mean age plus of minus standard deviation 0.98 +/- 0.47).
      Followup was obtained in 31 children. There was no postoperative urinary
      retention, fistulas or meatal stenosis. No unusual or prolonged discomfort
      distinguished these children from those who underwent a standard Thiersch-Duplay
      repair. CONCLUSIONS: Excellent cosmetic results can be anticipated irrespective
      of the preoperative glans configuration. Incision of the glanular urethral plate
      can be performed safely as an adjunct to a modified Thiersch-Duplay hypospadias
      repair without postoperative indwelling catheters.

PMID- 9258167
TI  - Scrotal cystic lymphangioma: the misdiagnosed scrotal mass.
AB  - PURPOSE: We report 7 cases of scrotal cystic lymphangioma and review the
      literature on this unusual lesion, which is often misdiagnosed as other
      conditions and treated incorrectly. MATERIALS AND METHODS: We retrospectively
      reviewed the medical records of 7 patients with scrotal cystic lymphangioma
      treated from 1984 to 1996 at 5 institutions. RESULTS: Mean patient age at
      presentation was 3 years and painless scrotal swelling was the most common
      symptom. Physical examination demonstrated an unusual cystic scrotal mass with a
      normal testis and cord in most patients, and ultrasound in 4 showed a complex
      septated cystic mass. Preoperative misdiagnosis in all 7 patients included
      hernia, hydrocele, hematocele, varicocele and possible torsion. In 6 children the
      lesions were more extensive than expected with deep perineal and/or inguinal
      involvement, including 2 who also had pelvic and retroperitoneal extension.
      Incomplete excision led to recurrence in 4 patients. CONCLUSIONS: Scrotal cystic
      lymphangioma presents as an unusual cystic scrotal mass. Although misdiagnosis
      has been common, awareness of the characteristic features of this lesion should
      lead to the correct preoperative diagnosis. When lymphangioma is suspected,
      imaging of the adjacent inguinal, perineal and pelvic regions should be
      performed. Complete excision is mandatory to prevent recurrence.

PMID- 9258168
TI  - A platelet activating factor antagonist attenuates the effects of testicular
      ischemia.
AB  - PURPOSE: Platelet activating factor, a biochemical marker and lipid mediator of
      ischemic injury, has been demonstrated in several organ systems. The objective of
      this study was to investigate the possible role of platelet activating factor in
      testicular ischemic injury. MATERIALS AND METHODS: Five groups of 6 male Sprague
      Dawley rats were studied, including group 1-nonoperated controls, group 2-sham
      operated controls, group 3-those that underwent administration of 10
      micrograms./kg. exogenous platelet activating factor into the left testicular
      artery, group 4-those that underwent 4 hours of testicular ischemia and group 5
      those that received pretreatment with 0.4 mg./kg. of the platelet activating
      factor antagonist CV-6209 intravenously before 4 hours of testicular ischemia.
      Ipsilateral and contralateral testes were examined histologically and
      seminiferous tubular diameters were measured. RESULTS: Exogenous platelet
      activating factor administration in group 3 and 4 hours of ischemia in group 4
      resulted in a similar extent of histological degeneration of the experimental
      testicle. Pretreatment with CV-6209 in group 5 resulted in a marked decrease in
      hemorrhagic discoloration, vascular congestion and histological changes noted
      with ischemia in group 4. CONCLUSIONS: The results of this study suggest that
      platelet activating factor has a biochemical role in tissue injury associated
      with testicular ischemia. Also, administration of a platelet activating factor
      antagonist before the ischemic event decreases seminiferous tubule degeneration.

PMID- 9258169
TI  - Epidemiological features of testicular teratoma in a prepubertal population.
AB  - PURPOSE: Prepubertal teratomas of the testis are rare benign tumors. Knowledge of
      the epidemiology of testicular teratomas and associated alpha-fetoprotein (AFP)
      levels could assist in planning treatment for prepubertal patients suspected of
      having teratoma of the testis. MATERIALS AND METHODS: We evaluated data on
      testicular teratoma from the Prepubertal Testis Tumor Registry of the Section on
      Urology of the American Academy of Pediatrics. RESULTS: Median patient age at
      presentation was 13 months. Teratomas occurred equally in the right and left
      testes. Most patients presented with a scrotal mass. Preoperative AFP levels were
      elevated in 20 of the 34 patients and postoperative levels were elevated in 9 of
      10. Most patients were treated with radical orchiectomy and no metastatic disease
      was reported. CONCLUSIONS: Data in the registry confirm the benign nature of this
      tumor. Normal AFP levels should not be expected in infants with teratoma.

PMID- 9258170
TI  - Treatment with a luteinizing hormone-releasing hormone analogue after successful
      orchiopexy markedly improves the chance of fertility later in life.
AB  - PURPOSE: Infertility has been considered a principal complication associated with
      cryptorchidism. A particularly high incidence of cryptorchid boys lack the
      priming effect during the first 3 months of life due to low concentrations of
      gonadotropins and testosterone (inadequate perinatal stimulation of the testes,
      which causes infertility). This condition causes impaired transformation of
      gonocytes into fetal spermatogonia. More pronounced hypogonadotropic hypogonadism
      results in fewer germ cells. Most importantly, cryptorchid boys with fewer than
      0.2 cells per tubular cross section have a high probability of being infertile in
      adulthood, regardless of whether the condition is unilateral or bilateral and
      despite apparently successful orchiopexy. MATERIALS AND METHODS: To counteract
      the paucity of priming hormones, cryptorchid patients with unilateral or
      bilateral cryptorchidism and a severe paucity of germ cells were treated with a
      low dose of the luteinizing hormone-releasing hormone analogue buserelin after
      successful orchiopexy. We analyzed the spermiograms of these patients, who are
      now young adults, and compared them to those of 23 other men who also had
      cryptorchidism with a comparable severe paucity of germ cells but who had not
      received hormonal treatment after successful orchiopexy. RESULTS: Patients who
      received hormonal therapy after orchiopexy had significantly improved
      spermiograms compared to those in the control group. Treatment with buserelin
      increased the number of spermatozoa, improved motility and increased the number
      of normal forms of spermatozoa. CONCLUSIONS: The luteinizing hormone-releasing
      hormone analogue buserelin, administered as a nasal spray every other day for 6
      months following successful orchiopexy, appears to have a long lasting, positive
      effect on germ cells. Consequently, the prognosis of fertility has been greatly
      enhanced in patients treated with buserelin.

PMID- 9258171
TI  - Management of neonatal testicular torsion.
AB  - PURPOSE: We evaluated the safety and efficacy of emergency exploration of
      neonatal torsion. MATERIALS AND METHODS: We retrospectively reviewed the charts
      of 27 neonates (30 affected testicles) in a 13-year period. RESULTS: Of the 10
      testicles that were explored and fixed within 6 hours of discovery 2 (20%) were
      normal at physical examination at 1 year of followup. Of the remaining 20
      testicles 19 were removed. One patient was lost to followup after orchiopexy. No
      operative or perioperative complications were associated with emergency
      exploration. CONCLUSIONS: Emergency exploration of neonatal torsion is safe and
      prudent, and may result in higher testicular salvage rates. Given reports of
      contralateral torsion, we also recommend contralateral orchiopexy.

PMID- 9258172
TI  - Critical analysis of the clinical presentation of acute scrotum: a 9-year
      experience at a single institution.
AB  - PURPOSE: We assessed the significance of the clinical presentation of boys who
      underwent surgical exploration for acute scrotum. MATERIALS AND METHODS: We
      retrospectively analyzed the records of 115 consecutive boys who underwent
      surgical exploration for acute scrotum between October 1986 and January 1996. We
      divided the children into group 1-83 with spermatic cord torsion a mean of 14.4
      years old, group 2-27 with torsion of a testicular appendage a mean of 9.4 years
      old and group 3-5 with epididymo-orchitis a mean of 14.1 years old. Particular
      attention was given to nausea and vomiting, patient age and duration of pain.
      RESULTS: Nausea and vomiting occurred in 69 and 60% of the boys in group 1, 8 and
      4% in group 2 and none in group 3. Nausea and vomiting had positive predictive
      values of 96 and 98%, respectively, for spermatic cord torsion. Only 6 of the 83
      boys (7%) with spermatic cord torsion were younger than 11 years, whereas 15 of
      the 27 (56%) with torsion of a testicular appendage were younger than 11 years.
      Of the 83 boys with spermatic cord torsion the testes were salvaged in 51 (61%)
      and the duration of pain was 40 minutes to 12 hours (mean 4 hours). The testes
      were not salvaged in any patient with greater than 12 hours of pain. CONCLUSIONS:
      We believe that any boy 11 years old or older with scrotal pain less than 12
      hours in duration that is associated with nausea or vomiting should be considered
      to have torsion of the spermatic cord. In this day of cost-effective medical
      management it is not necessary to perform imaging in this subset of boys before
      surgical exploration.

PMID- 9258173
TI  - The influence of surgical approach and intraoperative venography on successful
      varicocelectomy in adolescents.
AB  - PURPOSE: We evaluated the importance of intraoperative venography and surgical
      approach on varicocele recurrence after surgical varicocelectomy in male
      adolescents. MATERIALS AND METHODS: The analysis was done using local data and
      composite data from the literature. We reviewed the records of patients
      undergoing varicocele ligation between 1986 and 1995 at our institution. Data
      were stratified by surgical approach and performance of venography, and compared
      by cross table analysis. Data were then compiled from the literature from series
      that included cases stratified according to surgical approach and/or performance
      of venography. The impact of these parameters on recurrence rates was assessed by
      computing success rates and cross table analysis. RESULTS: At our institution 33
      boys underwent ligation via a suprainguinal (27) or inguinal (8) approach.
      Intraoperative post-ligation venography was performed in 16 cases and omitted in
      19. Neither surgical approach nor performance of venography influenced the
      recurrence rate in these patients (not statistically significant). Similarly,
      venography did not affect the recurrence rate after stratification by surgical
      approach (not significant). The overall success rate was 97% (34 of 35 cases).
      These data were added to those of 3 published studies, totaling 252 varicoceles
      with comparable groupings. Mean success rate after a suprainguinal and inguinal
      approach was 95.6 (93.2 to 97.4) and 88.3% (82.7 to 100%), respectively.
      Recurrence tended to be less common after a suprainguinal than an inguinal
      approach (p = 0.06). Post-ligation venography did not statistically affect the
      success rate after stratification according to surgical approach but it was
      associated with a higher success rate when performed with the inguinal approach.
      CONCLUSIONS: Irrespective of the performance of venography, the suprainguinal
      surgical approach yields higher success rates than the inguinal approach to
      varicoceles in adolescents. Post-ligation intraoperative venography fails to
      affect significantly the success of varicocele ligation but it may be useful
      during an inguinal approach.

PMID- 9258174
TI  - Two-stage Fowler-Stephens orchiopexy with laparoscopic clipping of the spermatic
      vessels.
AB  - PURPOSE: We report the outcome of a staged approach to the intra-abdominal
      testicle and provide baseline data on operative time, postoperative course and
      testicular survival. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 441 boys (547 undescended testes). There were 105 boys (24%) with 124
      nonpalpable testes (23%). All patients underwent laparoscopy. Ligation of
      spermatic vessels was performed as stage 1 on 20 abdominal testes (4%) in 18 boys
      (4%). Stage 2 orchiopexy was done using an open technique. RESULTS: Two-stage
      orchiopexy in 18 boys included a bilateral procedure in 2, of which 1 was
      asynchronous and 1 was synchronous. Average operative time was 55 minutes for
      stage 1 and 67 minutes for stage 2. Stage 1 and 2 procedures were performed on an
      outpatient basis in 18 and 17 (94%) boys, respectively. There were no
      complications after stage 1 and 1 wound infection developed after stage 2. One
      testis with no vas deferens was determined to be nonviable at stage 2. The
      remaining 19 testes (95%) were considered viable at a followup of 6 months or
      greater. Viability was based on testicular size and consistency similar to those
      of the contralateral testis. CONCLUSIONS: Laparoscopic ligation of spermatic
      vessels as a stage 1 procedure is a natural extension of laparoscopy. A staged
      approach provides adequate viability of the intra-abdominal testis.

PMID- 9258175
TI  - GAX 65: new injectable cross-linked collagen for the endoscopic treatment of
      vesicoureteral reflux--a double-blind study evaluating its efficiency in
      children.
AB  - PURPOSE: In the experimental model glutaraldehyde cross-linked collagen GAX 65
      with a collagen concentration of 65 mg./ml. has proved to have more persistent
      implant volume and, therefore, a better antireflux effect than GAX 35, which is
      injected more commonly. The aim of this study was to evaluate the potential
      clinical application of GAX 65. MATERIALS AND METHODS: Ten boys and 8 girls an
      average of 4.6 years old presented with unilateral or bilateral primary reflux
      and were randomly divided into 2 groups. All refluxing ureters received 1
      endoscopic subureteral injection of an average of approximately 2.9 ml. collagen.
      In group 1, 16 refluxing ureters were treated with GAX 65 and in group 2, 12 were
      treated with GAX 35. In all patients voiding cystourethrography was performed
      immediately after injection and 3 months postoperatively, and ultrasound was done
      on day 1, and at 1 and 3 months. Implant volume was calculated at the day of
      injection and at 3 months. The distribution of reflux grades was comparable in
      the 2 groups. RESULTS: Both materials had excellent injection properties.
      Immediately after injection all ureters were reflux-free. Of the 16 ureters
      treated with GAX 65 14 (87.5%) were reflux-free at the 3-month followup. Three
      months postoperatively ultrasound revealed an average implant volume increase of
      one-third. However, of the 12 ureters treated with GAX 35 reflux had resolved in
      59.3% and the average implant volume had decreased by half 3 months after
      injection. CONCLUSIONS: Three months after endoscopic subureteral injection of
      GAX 65 vesicoureteral reflux was absent in 87.5% of patients. Therefore, GAX 65
      has greater potential for treating reflux in the short term than GAX 35. To
      define the final efficacy of GAX 65 for treating vesicoureteral reflux, long-term
      evaluation of this series is necessary. In addition, further studies are
      mandatory to prove the long-term advantage of this new injectable substance.

PMID- 9258176
TI  - Newly diagnosed contralateral reflux after successful unilateral endoscopic
      correction: is it due to the pop-off mechanism?
AB  - PURPOSE: Our aim was to analyze the incidence of newly diagnosed contralateral
      vesicoureteral reflux after successful endoscopic correction of unilateral reflux
      by subureteral Teflon (polytetrafluoroethylene) injection and to explain the
      possible mechanisms responsible for new contralateral reflux. MATERIALS AND
      METHODS: A total of 1,195 children underwent successful endoscopic correction of
      high grade primary and duplex grades III to V vesicoureteral reflux by
      subureteral polytetrafluoroethylene injection. Unilateral and bilateral reflux
      was noted in 495 and 700 children, respectively. The 495 cases of unilateral
      reflux were retrospectively analyzed for new contralateral reflux. Voiding
      cystourethrography was performed in all cases 3 months and 1 year after
      injection. RESULTS: New contralateral reflux was diagnosed in 37 children (7%),
      including reflux in a single system in 33 and into a lower pole of a completely
      duplicated system in 4. There was no correlation of grade of ipsilateral reflux
      with the subsequent development of new contralateral reflux. No abnormality of
      the contralateral ureteral orifice was identified at initial cystoscopy, except
      for laterally placed ureteral orifices in 2 patients. CONCLUSIONS: The low
      incidence of new contralateral vesicoureteral reflux diagnosed after subureteral
      polytetrafluoroethylene injection versus open ureteral reimplantation may be due
      to noninterference with the contralateral trigone in endoscopic correction. The
      risk of new contralateral reflux did not increase with reflux severity (grades IV
      and V), suggesting that the pop-off mechanism is unlikely to be the cause of
      contralateral reflux.

PMID- 9258177
TI  - Contralateral ureteral meatal advancement in unilateral antireflux surgery.
AB  - PURPOSE: Contralateral vesicoureteral reflux is a well-known development after
      successful unilateral ureteral reimplantation that is not apparently influenced
      by the reimplantation technique. We sought to determine whether bilateral
      reimplantation should be performed routinely in unilateral cases. MATERIALS AND
      METHODS: From 1984 to 1995 we performed contralateral ureteral meatal advancement
      in 53 children 1 to 9.5 years old (mean age 2.5) undergoing surgery for
      unilateral grades II to V vesicoureteral reflux, including 12 with reflux in
      duplex systems. Ureteral meatal advancement involves a transverse Y shaped
      mucosal incision from the nonrefluxing orifice to the opposite hemitrigone. The
      inferior half of the ureteral orifice is then advanced toward the midline using 3
      or 4 long-term resorbable sutures. The control group included 98 children who
      underwent unilateral surgery for grades II to V reflux from 1990 to 1995.
      RESULTS: No evidence of vesicoureteral reflux was observed in the 53 children who
      underwent contralateral meatal advancement. There was no obstruction or other
      complications. At followup contralateral reflux was found in 11 controls after
      unilateral reimplantation. CONCLUSIONS: Contralateral reflux has been reported in
      up to 27% of previously reported cases and in 11% of our control group after
      successful unilateral antireflux surgery. Contralateral ureteral meatal
      advancement has proved effective for preventing reflux in 100% of cases. It
      requires minimal invasion of the nonrefluxing ureter, and little additional
      operative time and cost.

PMID- 9258178
TI  - Contralateral vesicoureteral reflux after simple and tapered unilateral
      ureteroneocystostomy revisited.
AB  - PURPOSE: We reviewed our experience with contralateral vesicoureteral reflux
      following unilateral ureteroneocystostomy. MATERIALS AND METHODS: We
      retrospectively identified 88 children who underwent unilateral
      ureteroneocystostomy from 1986 through 1995, including standard repair in 69 and
      tapered repair in 19. Cystoscopy was performed in all cases immediately before
      repair. RESULTS: Grades IV to V vesicoureteral reflux was identified
      preoperatively in 34% of the patients, including 13 (19%) and 14 (74%) who
      underwent standard and tapered repair, respectively. Renal duplication was noted
      in 24% of the cases, including 18 standard (26%) and 3 tapered (16%) repairs. An
      abnormal contralateral nonrefluxing ureteral orifice was present in 8 of the 53
      standard (15%) and 3 of the 14 (21%) tapered cases. Ipsilateral reflux was
      corrected in all children undergoing standard repair but it persisted in 4 (21%)
      in the tapered repair group. Postoperatively contralateral vesicoureteral reflux
      developed in 1 child (1.4%) in the standard and 1 (5.3%) in the tapered repair
      group. CONCLUSIONS: Contralateral vesicoureteral reflux is rare and does not
      appear to be influenced by preoperative reflux grade, a duplicated system or the
      endoscopic appearance of the ureteral orifice.

PMID- 9258179
TI  - Clinical care pathway for the management of ureteroneocystostomy in the pediatric
      urology population.
AB  - PURPOSE: The management of vesicoureteral reflux continues to evolve. Endoscopic
      and laparoscopic techniques have been reported as alternatives to standard
      surgical techniques. However, the newer modalities have no long-term track record
      and there is some question as to efficacy. We sought to establish a clinical care
      pathway for managing ureteroneocystostomy in children. MATERIALS AND METHODS: In
      the last 4 years we have developed a management technique based on a clinical
      collaborative care pathway with the help of surgeon, house staff, clinical nurse
      specialist and support personnel, that is floor, operating room and post
      anesthesia nurses. The pathway includes extensive preoperative parent and child
      education, standard intraoperative management and postoperative care without
      catheter drainage. It is based on a postoperative hospital stay of 2 days without
      a ureteral or urethral catheter. We report on the care of 110 consecutive
      patients (190 ureters) who underwent simple or common sheath ureteroneocystostomy
      from April 1992 to July 1996. RESULTS: No patient required the use of a urethral
      catheter or ureteral stent. Average length of hospital stay was 2.8 days and
      there were no immediate postoperative complications. At an average followup of 26
      months (range 5 to 53) an overall success rate of 97% per patient and 98% per
      ureter was achieved. Analysis of the costs of simple and common sheath
      ureteroneocystostomy in the clinical care pathway revealed a 4% increase over
      those in an ideal case with no deviations from the pathway. Costs and length of
      hospital stay were then compared to those for institutions of the university
      hospital consortium and they were found to be 39 and 45% less, respectively.
      Outcome based analysis by telephone interview revealed 100% patient or parent
      satisfaction. CONCLUSIONS: We believe that the management of vesicoureteral
      reflux using a coordinated clinical care pathway significantly improves length of
      hospitalization and inpatient costs with a high satisfaction score from parents
      and patients. This health care delivery style provides a standard to which other
      vesicoureteral reflux procedures must be compared.

PMID- 9258180
TI  - What imaging studies are necessary to determine outcome after
      ureteroneocystostomy?
AB  - PURPOSE: After ureteroneocystostomy we have performed renal ultrasonography
      within the first 3 months to exclude hydronephrosis, voiding cystography after 3
      months to exclude vesicoureteral reflux and subsequent ultrasonography to monitor
      the upper tracts. This study attempted to determine those patients at risk for
      hydronephrosis or recurrent vesicoureteral reflux. MATERIALS AND METHODS: We
      studied the records of patients who underwent ureteroneocystostomy in the last
      decade at our institutions to find the incidence and degree of preoperative and
      postoperative hydronephrosis and vesicoureteral reflux. Results of initial
      postoperative imaging were compared to radiological imaging throughout followup
      (mean 2.3 years). Patients with postoperative reflux were evaluated for risk
      factors that differentiated them from others. RESULTS: Excluding patients with
      neuropathic bladder or ureterocele, 167 underwent 278 ureteroneocystostomies at a
      mean followup of 26.5 months. Persistent vesicoureteral reflux was noted in 4
      kidneys (1.4%) and contralateral reflux developed in 3 of the 48 cases (6.3%) of
      unilateral ureteroneocystostomy. There was no statistical difference in success
      rates among cross-trigonal, ureteral advancement or extravesical techniques. New
      onset mild hydronephrosis in 13 kidneys (4.7%) at the initial followup study
      (mean 1.6 months) completely resolved in 12 and remained mild in 1. No patient
      had progression of existing hydronephrosis and 1 had recurrent vesicoureteral
      reflux after initial negative cystography. Risk factors for postoperative reflux
      or hydronephrosis were preoperative dysfunctional voiding, preoperative
      hydronephrosis or scarring on sonography and postoperative urinary tract
      infection. None of the 88 patients without these risk factors had postoperative
      hydronephrosis or reflux. All patients with persistent, contralateral or
      recurrent reflux were selected using these criteria (p < 0.003). CONCLUSIONS:
      Complication rates after nontapered ureteroneocystostomy in children without
      neuropathic bladder are quite low. Mild postoperative hydronephrosis was not
      clinically significant in our patients. Children with abnormal preoperative
      ultrasound or dysfunctional voiding are identified as a high risk group for
      postoperative hydronephrosis or recurrent reflux. All other patients received
      little benefit from postoperative imaging, suggesting that further evaluation of
      this group is necessary only in the presence of a postoperative urinary tract
      infection.

PMID- 9258181
TI  - Voiding cystourethrography after uncomplicated ureteral reimplantation in
      children: is it necessary?
AB  - PURPOSE: Our aim was to assess whether a voiding cystourethrogram after
      uncomplicated ureteral reimplantation is necessary or cost-efficient. MATERIALS
      AND METHODS: We retrospectively reviewed the records of patients who underwent
      uncomplicated reimplantation at our institution from 1988 to 1994. We also
      reviewed the literature to tabulate the reflux resolution rate from all published
      series of more than 100 ureters reimplanted. RESULTS: At our institution 119
      patients (207 ureters) underwent uncomplicated reimplantation and a postoperative
      voiding cystourethrogram, which documented a 98.6% initial reflux resolution
      rate. All persistent postoperative reflux resolved spontaneously without
      treatment for a final resolution rate of 100%. We reviewed 1,494 abstracts using
      vesicoureteral reflux as a key word and found 19 series of more than 100 ureters
      reimplanted. The combined results of our series and those 19 from the literature
      revealed 3,346 patients (5,008 ureters reimplanted). The final reflux resolution
      rate was 98.58%. Series that included and excluded secondary vesicoureteral
      reflux documented final reflux resolution rates of 98.4 and 99.04%, respectively.
      Reflux resolved spontaneously in 85% of the ureters in which it was noted on the
      initial postoperative cystogram. At our institution the cost of a voiding
      cystourethrogram is $610 and we perform an average of approximately 20
      uncomplicated reimplantations per year. In the United States there are
      approximately 230 pediatric urologists. If each surgeon performed 20
      reimplantations per year at the same cost per voiding cystourethrogram, a cost
      savings of $2.8 million per year would result if the study were not performed
      after surgery. CONCLUSIONS: In the hands of experienced pediatric urologists
      uncomplicated ureteral reimplantation has a success rate of 99.04%. The yield of
      postoperative voiding cystourethrography is exceedingly low and a cost savings of
      $2.8 million per year would result by omitting the postoperative voiding
      cystourethrogram.

PMID- 9258182
TI  - The use of renal parenchymal area in children with high grade vesicoureteral
      reflux.
AB  - PURPOSE: We sought to apply 2-dimensional sonographic measurements of renal
      parenchymal area in children with high grade vesicoureteral reflux to assess
      reliability and accuracy in estimating differential renal function, and in
      predicting clinical outcome compared to traditional 1-dimensional sonographic
      measurements. MATERIALS AND METHODS: We retrospectively evaluated 121 sonograms
      from 30 patients with a grade 4 or 5 primary vesicoureteral reflux, including 14
      who underwent ureteral reimplantation during followup and 16 who were followed on
      prophylactic antibiotic therapy. One-dimensional sonographic measurements of
      longitudinal length and bipolar thickness were determined in refluxing and
      contralateral kidneys, as were 2-dimensional measurements of longitudinal
      parenchymal area using computer planimetry. Renal length, bipolar thickness and
      parenchymal area were compared to renal function data determined by nuclear
      renography. Renal length and area was also represented as a percent of age
      adjusted normal values using previously published nomograms. RESULTS:
      Differential renal function correlated well with differential parenchymal area
      for all patients (r = 0.924). This correlation persisted in patients with (r =
      0.917) and without scarring (r = 0.890), as determined by dimercapto-succinic
      acid scan. Differential length did not correlate as well (r = 0.661) and bipolar
      parenchymal thickness did not correlate at all (r = 0.021). Sonographic age
      adjusted area of the refluxing kidneys was approximately two-third normal. No
      statistically significant difference was observed among age adjusted renal area
      of the observation, preoperative and postoperative groups. Contralateral kidney
      area was not significantly different than normal. CONCLUSIONS: Our data indicate
      that serial sonographic measurements of longitudinal renal parenchymal area
      provide a simple and accurate method of monitoring renal growth and function in
      patients with high grade vesicoureteral reflux. In contrast to 1-dimensional
      measurements of renal length and bipolar parenchymal thickness, renal parenchymal
      area correlates well with renal function. Area also appears to be a more
      sensitive method of monitoring renal growth in children with vesicoureteral
      reflux.

PMID- 9258183
TI  - Urodynamics and massive vesicoureteral reflux.
AB  - PURPOSE: Urodynamic studies are the key to management and reconstruction of
      bladder pathology. In the face of high grade vesicoureteral reflux measured
      pressures and volumes reflect the combined storage characteristics of the upper
      and lower tracts. We examined the influence of high grade reflux on measured
      volume and compliance (change in volume/change in pressure). MATERIALS AND
      METHODS: A total of 18 children with high grade vesicoureteral reflux underwent
      urodynamic evaluation with and without ureteral occlusion. Occlusion was created
      in the operative suite using ureteral occlusion balloons. After fluoroscopic
      confirmation of the absence of reflux bladder pressure was measured during
      filling at a rate of 12.5 cc per minute. During ureteral occlusion bladder
      capacity was defined as leakage around the urethral catheter, bladder pressure
      greater than 40 cm. water or volume exceeding estimated bladder capacity for age,
      as determined by the formula, bladder capacity in ml. = (age + 2) x 30. The
      ureteral occlusion balloons were removed and similar measurements were obtained
      in the presence of reflux. Compliance was calculated for the first and last 50%
      (initial and terminal compliance, respectively) of bladder capacity. RESULTS:
      Mean initial compliance without and with ureteral occlusion was 19.6 versus 13.2
      cm. water (33% decrease). Mean terminal compliance without and with occlusion was
      12.9 versus 8.6 cm. water (33% decrease, p < 0.005). Bladder capacity decreased a
      median of 16%. Underlying bladder pathology was evaluated to determine the
      patients who would benefit most from ureteral occlusion studies. Patients with
      neurogenic bladder, posterior urethral valves and primary reflux had similar
      changes in measured compliance with ureteral occlusion. Patients with poor
      terminal compliance without occlusion and those with bilateral vesicoureteral
      reflux had greater changes in compliance with occlusion but these changes were
      not statistically significant (p < 0.05). Age was indicative of a significant
      decrease in terminal compliance with ureteral occlusion, since older patients had
      the greatest change in terminal compliance (p < 0.005). CONCLUSIONS: High grade
      vesicoureteral reflux influences measured lower tract volume and compliance.

PMID- 9258184
TI  - Hypertension after surgical management of renal duplication associated with an
      upper pole ureterocele.
AB  - PURPOSE: Duplicated upper pole systems associated with a ureterocele frequently
      have areas of segmental renal dysplasia. Since dysplasia has been related to the
      development of renin mediated hypertension, we hypothesized that preservation of
      functional upper pole moieties may result in an increased incidence of high blood
      pressure. MATERIALS AND METHODS: We evaluated 115 patients with a history of
      renal duplication and an ipsilateral upper pole ureterocele. Patients were
      separated into group 1-nonfunctional upper pole managed by partial nephrectomy,
      group 2-functional upper pole moiety managed by partial nephrectomy and group 3
      functional upper pole moiety managed by a nephron sparing procedure. All charts
      were reviewed for hypertension, febrile urinary tract infection, vesicoureteral
      reflux and renal scarring. RESULTS: At a median followup age of 15 years (range 1
      to 33) hypertension developed in 13 of the 115 patients (11%), including 8 of the
      87 (9%) with nonfunctional upper pole systems managed by partial nephrectomy, 1
      of the 12 (8%) with a functional upper pole moiety managed by partial nephrectomy
      and 4 of the 16 (25%) with a functional upper pole system managed by an upper
      pole salvage procedure. Statistical evaluations failed to reveal any relationship
      between hypertension and preservation of the upper pole system or between
      hypertension and vesicoureteral reflux. Rather, elevation in blood pressure was
      found to be related to development of a renal scar after a febrile urinary tract
      infection. CONCLUSIONS: Hypertension in patients with a history of renal
      duplication associated with a ureterocele is directly related to renal scarring.

PMID- 9258185
TI  - Management of ectopic ureters: experience with the upper tract approach.
AB  - PURPOSE: The necessity of removing the ureteral stump after upper tract surgery
      for an ectopic ureter has been debated. We reviewed the records of patients
      initially treated at the kidney level to evaluate indications for later stump
      removal. MATERIALS AND METHODS: We reviewed the medical records of 32 patients
      with 33 ectopic ureters treated at the kidney level during the last 10 years.
      RESULTS: Ectopic ureters were associated with duplicated collecting systems in 31
      cases and with single systems in 2. Upper pole heminephrectomy and partial
      ureterectomy were performed in 23 units and upper tract reconstruction was done
      in 8. Both patients with single systems underwent nephrectomy. Four patients
      (12%) required repeat surgery at the bladder level, including 1 who underwent
      ureteral reimplantation for persistent ipsilateral lower pole reflux and
      simultaneous upper pole stump removal. Preoperative voiding cystourethrography
      revealed reflux into the ectopic ureter in 1 patient with postoperative reflux
      and infections. The remaining 2 patients required a repeat operation to remove
      the stump due to recurrent urinary tract infections and newly detected reflux
      into the stump, respectively. CONCLUSIONS: The majority of patients with ectopic
      ureters can be treated by addressing only the upper urinary tract. No patient who
      presented with incontinence required ureteral stump removal. Whether noted
      preoperatively or postoperatively, reflux into the ectopic ureter necessitated
      ureteral stump removal. Three of the 6 patients (50%) who had reflux to the
      ipsilateral kidney required lower tract surgery.

PMID- 9258186
TI  - Reliability of 99mtechnetium dimercapto-succinic acid uptake 2 hours after
      injection in hydronephrosis.
AB  - PURPOSE: The accumulation of radioactivity in the dilated collecting system
      potentially influences the calculation of differential renal function on the
      radionuclide test. We focused on this reservoir effect in unilateral
      hydronephrosis and assessed the reliability of calculating differential renal
      function by dimercapto-succinic acid (DMSA) uptake 2 hours after injection.
      MATERIALS AND METHODS: Unilateral partial ureteral obstruction was created in 8
      week-old rats. Four weeks after surgery the animals were sacrificed 2 and 24
      hours after the injection of tracer. The DMSA uptake rates of the renal
      parenchyma and collecting system were measured separately by autowell gamma
      counter. Differential function was calculated according to renal parenchymal and
      whole kidney (parenchyma and collecting system) uptake. RESULTS: There was a
      higher accumulation of DMSA in the dilated renal pelvis at 2 than at 24 hours.
      However, DMSA uptake in the collecting system was extremely small in comparison
      to that in the parenchyma. As a result; differential renal function calculated
      using parenchymal uptake was similar to that calculated using whole kidney uptake
      measured 2 and 24 hours after injection. CONCLUSIONS: Our data suggest that the
      pure reservoir effect of DMSA uptake at early measurement is much smaller than
      reported in previous experimental animal studies. Further clinical studies are
      needed to reexamine this reservoir effect in children with unilateral
      hydronephrosis.

PMID- 9258188
TI  - The operative management of recurrent ureteropelvic junction obstruction.
AB  - PURPOSE: Surgical repair of ureteropelvic junction obstruction is successful in
      98% of cases. We evaluated children undergoing repeat pyeloplasty and discuss the
      etiology of recurrent ureteropelvic junction obstruction, surgical approach and
      outcome. MATERIALS AND METHODS: Between 1982 and 1996, 366 children with
      ureteropelvic junction obstruction were surgically treated at our institution,
      including 16 who presented with recurrent ureteropelvic junction obstruction and
      required surgery. RESULTS: Repeat repair was successful in all 16 patients,
      including ureterocalicostomy in 3 and dismembered pyeloplasty in the remainder.
      No nephrectomy was necessary. Anteriorly elongated flank incisions were made in
      all cases. Dense scar tissue around and obstructing the ureteropelvic junction
      was noted in the majority of cases. In 7 patients a redundant pelvis resulted in
      a kink at the ureteropelvic junction. A nephrostomy tube was placed in all cases
      and an additional transanastomotic stent was used in all but 2. Obstruction was
      relieved with 1 operation. CONCLUSIONS: A redundant pelvis resulting in a kink at
      the ureteropelvic junction may contribute to a higher change of urinary leakage
      and subsequent obstructive scar formation in cases of failed pyeloplasty. Before
      repeat surgery anatomy should be precisely identified by antegrade and retrograde
      studies. The surgical approach usually involves identifying the ureter below the
      area of the previous surgery and then ensuring a tension-free anastomosis. If
      inadequate ureteral length or an intrarenal pelvis precludes direct anastomosis,
      ureterocalicostomy is an alternative. A nephrostomy tube and transanastomotic
      stent are advisable. Nephrectomy is rarely necessary and a good functional result
      can be anticipated.

PMID- 9258187
TI  - Changing the technique of background subtraction alters calculated renal function
      on pediatric mercaptoacetyltriglycine renography.
AB  - PURPOSE: Although many operative decisions are based on apparent changes in
      function detected by serial diuretic renography, the reliability of relative
      renal function data has been questioned. We investigated the effect of background
      subtraction on calculated renal function. MATERIALS AND METHODS: We reviewed 23
      pediatric mercaptoacetyltriglycine renograms. Regions of interest for background
      subtraction were redrawn and relative renal function values were recalculated.
      RESULTS: In patients with left hydronephrosis left differential renal function
      was consistently underestimated by 7.3% compared to the superior and 4.7%
      compared to the average background subtraction technique. In patients with right
      hydronephrosis, when considering lower pole background activity only, right
      differential renal function was consistently overestimated by 15.8% compared to
      the superior and 2.4% compared to the average background subtraction technique.
      In patients younger than 1 year at the time of study these differences were
      exaggerated. CONCLUSIONS: Because of overlapping hepatic background activity, the
      position of regions of interest for background subtraction may greatly influence
      calculated renal function. We recommend that the preferred method of calculating
      background subtraction to minimize error be based on a region of interest
      surrounding the whole kidney. This method is especially pertinent in patients
      with right hydronephrosis and in those younger than 1 year. Reported relative
      renal function data should be interpreted with caution.

PMID- 9258190
TI  - Age related bladder capacity and bladder capacity growth in children with
      myelomeningocele.
AB  - PURPOSE: Currently the relationship between bladder capacity and age in children
      with myelomeningocele is inadequately understood, such that nomograms derived
      from neurologically normal children are inappropriately applied to the
      myelodysplastic population. The aim of the present study was to evaluate age
      related bladder capacity and bladder capacity growth in children with
      myelomeningocele, and compare them to those of age matched, neurologically intact
      children. MATERIALS AND METHODS: Bladder capacity was determined by
      cystometrography in children with myelodysplasia. Regression analysis was used to
      derive a relationship between bladder capacity and patient age. Data were
      stratified by sphincter activity, bladder sensation and uninhibited contractions,
      and regression analysis was repeated. To evaluate serial growth change in bladder
      capacity divided by time yielded a yearly bladder capacity growth rate in
      patients who underwent 2 cystometrograms done at least 3 months apart before age
      9 years. RESULTS: A total of 506 children satisfied study inclusion criteria.
      Bladder capacity (BC) was related to age for the first 9 years by the linear
      equation, BC = 24.5 (age) + 62. This equation is approximately 25% less steep
      than published age related bladder capacity in neurologically intact children
      using the formula, 32 (age) + 73. After data stratification bladder capacity in
      children with sphincter activity, bladder sensation or no uninhibited
      contractions approached that of neurologically intact children. In contrast,
      children without sphincter activity or bladder sensation, or with uninhibited
      contractions had markedly smaller age related bladder capacity. Bladder capacity
      growth in the subgroup of 55 children in whom 2 cystometrograms were performed at
      least 3 months apart before age 9 years confirmed a mean gain in capacity of 24
      cc per year. CONCLUSIONS: Normal bladder capacity in children with myelodysplasia
      is approximately 25% less than in age matched, neurologically intact children.
      The bladder grows approximately 24 cc per year until age 9 years. When there is
      failure to store urine, bladder capacity is much smaller, while children with
      good storage features may attain the bladder capacity expected of age matched,
      neurologically intact children.

PMID- 9258191
TI  - A renal size nomogram for the patient with myelomeningocele.
AB  - PURPOSE: Renal anatomy and function are usually monitored in the myelomeningocele
      population using routine ultrasound as the child grows. Clinical questions arise
      when a renal unit is of marginal size when evaluated with nomograms derived from
      normal patient populations. Our goal was to construct a renal size nomogram using
      ultrasound for the myelomeningocele population to help the clinician identify
      abnormal growth. MATERIALS AND METHODS: We reviewed the charts and radiological
      files of 96 patients with myelomeningocele followed at our institution. Images of
      930 renal units were included to construct the nomogram. Patients were excluded
      from study due to hydronephrosis or hydroureter, solitary kidney, recurrent
      symptomatic urinary tract infection, vesicoureteral reflux, reconstructive
      surgery or known high bladder storage pressure. RESULTS: A renal size nomogram
      was constructed by plotting patient age against maximal renal length on real-time
      ultrasound. Expected mean and standard deviations were calculated for each age
      group. CONCLUSIONS: Previous studies using excretory urography have shown that
      kidneys in the myelomeningocele population are smaller than in a healthy control
      population. Ultrasound is now the modality most commonly used to monitor renal
      anatomy. The creation of a renal nomogram based on ultrasound should help the
      clinician identify abnormal renal growth more accurately.

PMID- 9258192
TI  - Pressure at residual volume: a useful adjunct to standard fill cystometry.
AB  - PURPOSE: Determining the role of the bladder in incontinence and/or upper urinary
      tract deterioration involves the cystometrographic evaluation of detrusor
      compliance. Management decisions based on information provided by standard fill
      water cystometry assume that data reflect the physiological state of the patient
      but this is not always true. We report the use of pressure at residual volume as
      a physiological measurement to aid in the interpretation of data obtained during
      standard fill urodynamics. MATERIALS AND METHODS: All patients presenting to our
      urodynamic suite for standard cystometry between June 1994 and December 1995
      underwent measurement of bladder pressure at insertion of the urodynamic
      catheter. Residual volume and pressure measured before draining this urine, that
      is pressure at residual volume, were recorded. The bladder was then filled at a
      rate equal to or less than 10% per minute of known or predicted capacity. When a
      volume equal to the residual volume had been instilled, filling pressure was
      recorded and the remainder of the standard urodynamic evaluation was completed.
      Uncooperative patients as well as those with an active infection or residual
      volume less than 10 ml. were excluded from further analysis. RESULTS: In 152
      children pressure at residual volume was compared to filling pressure and the
      difference was analyzed. Filling pressure was higher than pressure at residual
      volume in the majority of cases. In 59 children there was a positive change
      (filling pressure greater than pressure at residual volume) of 5 cm. water or
      greater and in 13 there was a negative change (pressure at residual volume
      greater than filling pressure) of 5 cm. water or less. When only cases in which
      pressure at residual volume was greater than 5 cm. water were analyzed, 46 and
      33% had a difference between filling pressure and pressure at residual volume of
      5 cm. water or greater and 10 cm. water or greater, respectively. CONCLUSIONS:
      Pressure at residual volume is physiological, simple to determine and may provide
      additional information regarding storage characteristics of the bladder. In the
      context of the clinical history differences between pressure at residual volume
      and filling pressure may help to interpret standard fill cystometry data.

PMID- 9258193
TI  - Initial experience with home therapeutic electrical stimulation for continence in
      the myelomeningocele population.
AB  - PURPOSE: In an attempt to enhance bladder and bowel continence 29 patients
      underwent long duration, low intensity transcutaneous therapeutic electrical
      stimulation. This technology has previously been shown to be effective for
      inducing regenerative hypertrophy of disuse atrophied skeletal muscle, and it has
      been associated with improved continence in the myelomeningocele population. Our
      objectives were to enhance urinary and fecal continence, and evaluate the
      mechanisms by which therapeutic electrical stimulation influences continence.
      MATERIALS AND METHODS: A total of 29 children with lumbar or sacral
      myelomeningocele underwent therapeutic electrical stimulation at home during
      sleep using a commercially available stimulator with a safety sensing circuit and
      2 sets of electrodes placed on the skin at bedtime. Left and right side electrode
      placement was alternated on 6 of 7 consecutive nights. In 9 boys and 2 girls with
      more than 9 months of followup initial and subsequent cystometrography, urethral
      pressure profile, electromyography, voiding cystourethrography and renal
      ultrasound studies were evaluated. RESULTS: In the 11 children there was no
      radiographic evidence of urinary tract or musculoskeletal deterioration during
      treatment. Mean actual bladder capacity increased from 133 to 196 ml. (p < 0.05).
      Mean bladder capacity, as a percent of maximum predicted bladder capacity for a
      normal age matched child without myelomeningocele, also significantly increased
      from 59 before to 76% after 9 months of therapeutic electrical stimulation (p <
      0.05). No significant change was noted in urethral pressure profile. A subjective
      improvement in the sensation of pelvic fullness was also observed. CONCLUSIONS:
      When administered at home by parents while the child sleeps, therapeutic
      electrical stimulation is safe for bladder and bowel continence in the
      myelomeningocele population. It seems to increase significantly bladder capacity,
      does not appear to change urethral pressure profile and results in a subjectively
      improved sensation of pelvic fullness, enhancing urinary and fecal continence.
      The most beneficial effect of therapeutic electrical stimulation seems to be on
      the bladder wall and less so on the striated pelvic floor musculature with
      subjective enhancement of pelvic fullness also contributing positively.

PMID- 9258194
TI  - Role of the antegrade continence enema in the management of the most debilitating
      childhood recto-urogenital anomalies.
AB  - PURPOSE: We evaluated the antegrade continence enema for managing the most
      severely compromised fecal continence mechanisms and the efficacy of
      nonappendiceal conduits in children when appendix is unavailable. MATERIALS AND
      METHODS: Ten patients 3 to 25 years old underwent continent cecostomy for the
      purpose of the antegrade continence enema. Diagnoses included the VATER
      association in 4 cases, myelomeningocele in 3, cloacal anomaly in 2 and isolated
      imperforate anus in 1. Eight patients received a tubularized ileal conduit, 2
      received an appendiceal conduit and 2 underwent concomitant fecal undiversion.
      RESULTS: Followup ranged from 4 to 28 months (mean 17.6). All patients have
      achieved excellent fecal continence and no significant stomal soilage or
      difficulty with catheterization has been noted. Patients reported a high degree
      of satisfaction. CONCLUSIONS: Continent cecostomy for the antegrade continence
      enema is highly effective even in the presence of severe structural anorectal
      disease. The tapered ileal conduit is an excellent alternative to the appendiceal
      conduit.

PMID- 9258195
TI  - The nonneurogenic neurogenic bladder of early infancy.
AB  - PURPOSE: The nonneurogenic neurogenic bladder has traditionally been believed to
      represent a disorder of older children. We report on patients in whom congenital
      dysfunctional voiding may be the underlying cause of nonneurogenic neurogenic
      bladder in early infancy. MATERIALS AND METHODS: We evaluated 5 male and 2 female
      patients newborn to 30 months old with dysfunctional neurogenic bladder and no
      evidence of neurological pathology or anatomical outflow obstruction.
      Presentation included prenatal hydronephrosis in 3 cases, urosepsis in 2 and
      failure to thrive in 2. Radiological and urodynamic investigations revealed thick
      walled, poorly compliant bladders in 5 patients and incomplete bladder emptying
      bordering on urinary retention in 2. There was significant upper tract pathology
      in all cases, including azotemia in 4, reflux in 4 and hydroureteronephrosis in
      6. Due to poor bladder function, manifested by incomplete emptying or high
      storage pressures, all patients were initially treated with cutaneous
      vesicostomy. RESULTS: Bladder appearance and function subsequently improved in 3
      patients and vesicostomy was reversed. Three patients with persistently thickened
      bladders, including 2 with renal failure, underwent bladder augmentation. The
      remaining patient had improved bladder storage function but requires intermittent
      catheterization. CONCLUSIONS: The nonneurogenic neurogenic bladder represents a
      rare, severe form of dysfunctional voiding that may be present even in the
      neonatal period.

PMID- 9258196
TI  - The urological manifestations of hollow visceral myopathy in children.
AB  - PURPOSE: Hollow visceral myopathy is a rare clinical entity characterized by
      impaired intestinal function in the absence of mechanical occlusion. It can
      affect the smooth muscle of the whole or segments of the gastrointestinal tract
      and occasionally the urinary tract. We examined the urological manifestations of
      hollow visceral myopathy and management in the pediatric population. MATERIALS
      AND METHODS: We reviewed the records of 14 male patients 1 day to 2 years old
      (mean age 4.6 months) and 10 female patients 1 day to 5 years old (mean age 9.4
      months) at presentation to our institution with hollow visceral myopathy. In all
      patients genitourinary tract ultrasound, voiding cystourethrography and serum
      creatinine measurement were done at presentation. RESULTS: All patients had
      gastrointestinal obstructive symptoms at presentation and 11 (46%) had urological
      symptoms, including urinary retention in 2, urinary tract infection in 3, and a
      prenatal diagnosis of megacystis and hydroureteronephrosis in 6. Overall 22
      patients (92%) had urological abnormalities, all had poor bladder emptying and
      recurrent urinary tract infections, and 13 had megacystis associated with
      bilateral hydroureteronephrosis in 9 and unilateral hydroureteronephrosis in 2.
      There were 9 deaths from extensive gastrointestinal involvement and sepsis. Of
      the surviving 15 patients 13 have urological abnormalities, including 8 who
      perform and tolerate clean intermittent catheterization via the urethra and are
      well. Of the 4 male infants who did not tolerate clean intermittent
      catheterization appendicovesicostomy was done in 1, a Casale tube was placed in 1
      and vesicostomy was performed in 2. The remaining female patient has day and
      night wetting. CONCLUSIONS: Urological abnormalities are common in hollow
      visceral myopathy and they can contribute to presenting symptoms. Clean
      intermittent catheterization via the urethra to aid in bladder emptying and
      decrease the frequency of urinary tract infections is the mainstay of treatment
      but surgery to construct an alternative catheterizable channel or vesicostomy may
      be required in intolerant patients.

PMID- 9258197
TI  - Frankie's story--spina bifida from the parents' perspective.

PMID- 9258198
TI  - Reconstruction of the high urogenital sinus: early perineal prone approach
      without division of the rectum.
AB  - PURPOSE: Reconstruction of the vagina and external genitalia in the infant is
      quite challenging, particularly when a urogenital sinus is associated with high
      confluence of the vagina and urethra. Many surgeons believe that children with
      such a malformation should undergo staged or delayed reconstruction, so that
      vaginoplasty is done when the child is older and larger. Vaginoplasty early in
      life is thought to be difficult due to patient size and poor visualization. The
      posterior sagittal approach has been beneficial for acquiring exposure to high
      urogenital sinus anomalies but it has been thought to require splitting of the
      rectum and temporary colostomy. We report a modification of this technique.
      MATERIALS AND METHODS: In the last 5 years all patients with urogenital sinus
      anomalies underwent reconstruction using a single stage approach regardless of
      the level of confluence. In 8 patients with a high level of confluence
      reconstruction was performed using a perineal prone approach. Exposure was
      achieved without division of the rectum. The operative technique is presented in
      detail. RESULTS: This midline perineal prone approach has allowed excellent
      exposure of the high vagina even in infants. In all 8 patients reconstruction was
      done without difficulty and no patient required incision of the rectum or
      colostomy. This procedure did not preclude the use of a posteriorly based flap
      for vaginal reconstruction. CONCLUSIONS: While patients with low confluence can
      be treated with single posteriorly based flap vaginoplasty, those with higher
      confluence may benefit from a perineal prone approach to achieve adequate
      exposure for pull-through vaginoplasty. This prone approach to the high
      urogenital sinus anomaly can be performed without division of the rectum,
      provides excellent exposure of the high confluence even in small children and
      does not preclude the use of posterior flaps for vaginal reconstruction.

PMID- 9258199
TI  - Genital malformations and coexistent urinary tract or spinal anomalies in
      patients with imperforate anus.
AB  - PURPOSE: Urinary tract malformations have been described in up to 50% of patients
      with imperforate anus but genital anomalies have been less well analyzed in the
      same patient population. We sought to evaluate the frequency of coexisting
      genital, urinary and spinal malformations in a population with imperforate anus.
      MATERIALS AND METHODS: We reviewed 128 cases of imperforate anus, focusing on
      genital malformations and their relationship to anomalies of the urinary tract
      and spine. The series included 69 boys and 59 girls with low (59), intermediate
      (22) and high (47) imperforate anus. RESULTS: Boys were much more likely to have
      a genital or upper urinary tract problem than girls (26 or 50 versus 5 or 30%,
      respectively). The risk for both sets of problems increased with the level of the
      anorectal lesion. The incidence of genital malformations increased from 14 to 26%
      in the presence of a renal lesion and from 10 to 23% with an associated spinal
      problem. Conversely, the incidence of urinary and spinal anomalies increased in
      patients with genital malformations. CONCLUSIONS: The genitalia of children with
      imperforate anus should be carefully examined. Patients with anorectal
      malformations should also be evaluated for urinary tract and spinal problems. The
      yield of such studies increases in patients with recognized genital
      malformations.

PMID- 9258200
TI  - The importance of accurate diagnosis and early close followup in patients with
      suspected multicystic dysplastic kidney.
AB  - PURPOSE: Conservative management of children who have unequivocal multicystic
      dysplastic kidney with a stable or regressive pattern of disease during close
      followup is well established. However, a clear diagnosis may prove difficult. We
      report 3 cases in which the diagnosis was particularly difficult to increase
      awareness of the importance of applying strict criteria for the diagnosis of
      multicystic dysplastic kidney. MATERIALS AND METHODS: Three children in whom a
      diagnosis of multicystic dysplastic kidney was suspected underwent surgical
      exploration. One patient who did not comply with followup presented with a large
      retroperitoneal mass suspicious for neuroblastoma 8 months later. In another
      patient a growing renal cystic mass was suspicious for a multilocular cyst at 3
      months of followup. At 2 months of followup a cystic nephroma was suspected in
      the remaining patient. RESULTS: All patients underwent surgical exploration. The
      patient with suspected neuroblastoma had extensive stage 3 Wilms tumor. In the
      child with a suspected multilocular cyst segmental multicystic dysplastic kidney
      of the lower pole of an ipsilateral duplicated system was found. In the patient
      in whom cystic nephroma was suspected mesoblastic nephroma was confirmed by the
      National Wilms Tumor Study Pathology Center. CONCLUSIONS: An unequivocal
      diagnosis of multicystic dysplastic kidney should be made early in life. The
      urologist should have an active role in making the initial radiological diagnosis
      and close followup with renal ultrasound every 3 to 4 months is essential during
      year 1 of life. Surgical exploration is indicated if the diagnosis becomes
      equivocal at any point or should concerns exist regarding compliance with
      followup.

PMID- 9258201
TI  - XX sex reversal: molecular analysis of the SRY/ZFY regions.
AB  - PURPOSE: The mammalian sex determining gene, sex region Y chromosome (SRY), is
      now firmly established as the testis determining locus. The SRY locus is close to
      the short arm Y terminus and just distal to zinc finger Y region (ZFY), a locus
      previously thought to be involved in testicular differentiation and the male
      phenotype. We report on XX sex reversal, a rare sex chromosomal disorder in
      humans. MATERIALS AND METHODS: Routine amniocentesis revealed an XX fetal
      karyotype, although at birth the neonate was phenotypically male. Radiographic
      evaluation showed a normal male urethra and the absence of any female internal
      genitalia. Subsequent molecular analysis with polymerase chain reaction amplified
      sequences of the SRY and ZFY loci were positive. RESULTS: This case is the fourth
      in our series of XX sex reversed male individuals and to our knowledge the first
      to be diagnosed perinatally. In all cases the SRY and ZFY loci are present,
      presumably on the paternal X chromosome, as well as a Klinefelter phenotype.
      These sex reversing translocations are thought to be due to an unequal meiotic
      recombination of the distal X and Y short arms during male gametogenesis. The
      tendency for XY translocations to break between the SRY and ZFY loci was not seen
      in these apparent microtranslocation cases. CONCLUSIONS: These 4 cases
      demonstrate the usefulness of molecular followup of clinically perplexing sexual
      discordance. We conclude that SRY and ZFY polymerase chain reaction amplification
      studies should be performed when sexual discrepancies are noted on prenatal
      ultrasound and karyotype analysis.

PMID- 9258202
TI  - Potential risk factors associated with progressive renal damage in childhood
      urological diseases: the role of angiotensin-converting enzyme gene polymorphism.
AB  - PURPOSE: Experimental as well as human studies have established an important role
      for the renin-angiotensin system in the progressive deterioration of renal
      function. Recently genetic polymorphism in components of the renin-angiotensin
      system has been associated with several cardiovascular diseases, particularly
      variations in the angiotensin-converting enzyme gene that involve insertion (I)
      or deletion (D) of a 287 bp fragment. The D variant has been associated with
      myocardial infarction and cardiac hypertrophy. MATERIALS AND METHODS: To assess
      whether this genetic variant is associated with worse prognosis in renal
      disorders we evaluated 70 children with congenital urological abnormalities,
      since a substantial number have progressive renal deterioration even after early
      corrective intervention. Renal deterioration was assessed by the presence or
      absence of radiographic evidence of parenchymal damage and serum creatinine.
      RESULTS: Among patients with no radiographic renal parenchymal damage angiotensin
      converting enzyme genotype distribution of II, ID and DD was 24, 67 and 9%,
      respectively. In contrast, a significantly different angiotensin-converting
      enzyme genotype distribution was observed in patients with evidence of
      parenchymal damage, that is 10, 49 and 41% for II, ID and DD, respectively (p <
      0.05, chi-square 5.0). Mean serum creatinine plus or minus standard error in the
      former group was normal at 0.6 +/- 0.1 mg./dl., while in those with scarring it
      was elevated at 1.1 +/- 0.1 mg./dl., as expected. In patients with the DD
      genotype an overwhelming frequency of parenchymal damage was observed, that is of
      all 22 with that genotype 20 (91%) had parenchymal damage. CONCLUSIONS:
      Considered together, these studies suggest that there are differences in the
      distribution of angiotensin-converting enzyme gene polymorphism in patients with
      congenital urological abnormalities who have evidence of renal parenchymal damage
      versus those who do not have such damage. Given that this genetic variation
      activates the renin-angiotensin system and this activation may be particularly
      robust in the kidney, we propose that the genotype of an individual independent
      of other factors modifies the likelihood of parenchymal loss in this setting.

PMID- 9258203
TI  - Insurability of children with congenital urological anomalies.
AB  - PURPOSE: We sought to determine life insurance underwriting practices for
      children diagnosed with multicystic dysplastic kidney or unilateral neonatal
      hydronephrosis, and evaluate whether management options (observation versus
      operative intervention) have an influence on such practices. MATERIALS AND
      METHODS: A questionnaire and history of 1 child with multicystic dysplastic
      kidney and 1 with unilateral neonatal hydronephrosis were distributed to 348
      insurance companies licensed to issue life insurance policies in New Jersey. The
      medical director of each insurance company was requested to indicate the current
      underwriting practices for life insurance policies based on these 2 case
      scenarios, and asked whether observation or operative intervention influenced
      such decisions. RESULTS: Of the 348 insurance companies licensed to issue life
      insurance 130 (37.4%) responded, including 5 (3.8%) that did not choose to
      participate in the study, 56 (43.1%) that did not issue life insurance to
      children and 69 (53.1%) that completed the questionnaire based on current life
      insurance underwriting practices. For a child with multicystic dysplastic kidney
      10 companies (14.5%) would issue life insurance if treatment involved observation
      only, while 49 (71%) would do so after nephrectomy. For a child with unilateral
      neonatal hydronephrosis 19 (27.5%) companies would issue life insurance if
      treatment involved observation only, while 46 (66.7%) would do so after
      pyeloplasty. CONCLUSIONS: Despite limited long-term data on and uncertainty about
      the natural course of multicystic dysplastic kidney and unilateral neonatal
      hydronephrosis, treatment options offered a child with a congenital urological
      anomaly may have a significant impact on the ability to obtain life insurance.
      Children with multicystic dysplastic kidney and unilateral neonatal
      hydronephrosis can usually obtain life insurance after early operative
      intervention (nephrectomy and pyeloplasty, respectively), although sometimes at
      higher cost.

PMID- 9258204
TI  - Ten years of experience with isolated urachal anomalies in children.
AB  - PURPOSE: The embryological and anatomical features of urachal anomalies have been
      well defined. Because of the variable clinical presentation, uniform guidelines
      for evaluation and treatment are lacking. In an attempt to establish a cost
      effective approach leading to a favorable outcome, we reviewed the experience
      with urachal anomalies at a single institution in a 10-year period. MATERIALS AND
      METHODS: We reviewed the medical records and radiological studies of 12 boys and
      9 girls newborn to 17 years old at presentation who were treated for a urachal
      anomaly. Diagnostic evaluation included voiding cystourethrography in 14 cases,
      ultrasound in 8, sinography in 7 and computerized tomography in 4. RESULTS: The 4
      variants of urachal anomalies included a urachal sinus in 9 patients (43%),
      urachal cyst in 9 (43%), patent urachus in 2 (10%) and urachal diverticulum in 1
      (4%). Treatment involved initial excision in 13 cases (61%) and secondary
      excision in 8 (39%). Staphylococcus aureus was the predominant organism
      recovered. CONCLUSIONS: Because of the variable presentation, the diagnosis of a
      urachal anomaly can be difficult. Our experience suggests that a cost-effective
      diagnostic approach can be developed based on the initial clinical evaluation.
      Whereas ultrasound is indicated when a urachal cyst or abscess is suspected on
      the initial study, sinography is the study of choice in the remainder of cases. A
      voiding cystourethrogram may not be required in view of the fact that none of the
      patients studied had an additional associated urinary tract anomaly.

PMID- 9258205
TI  - The role of percutaneous nephrolithotomy in the management of pediatric renal
      calculi.
AB  - PURPOSE: Minimally invasive techniques for the treatment of urinary calculi in
      children are recommended due to an increased probability of recurrence.
      Percutaneous nephrolithotomy is well established in adults but to our knowledge
      this procedure has not been reported previously in a large series of children. We
      review our experience with percutaneous nephrolithotomy in children. MATERIALS
      AND METHODS: From 1987 to 1995 percutaneous nephrolithotomy was performed in 25
      children 3 to 16 years old (median age 8). Indications for percutaneous
      nephrolithotomy were an obstructed kidney in 10 cases, large stone size or
      staghorn calculus in 8, failed extracorporeal shock wave lithotripsy in 4 and
      residual stones after open surgery in 3. There were 15 solitary renal, 4 staghorn
      and 2 upper ureteral stones, and 5 children had multiple renal calculi. RESULTS:
      Percutaneous nephrolithotomy was performed once in 22 patients, and 2, 3 or 5
      times in the remainder. Of the 25 patients 17 (68%) were stone-free at hospital
      discharge or shortly thereafter following a single session of percutaneous
      nephrolithotomy. Retained calculi after a single percutaneous nephrolithotomy
      treatment were much more common with staghorn stones (2 of 4 cases or 50%) and
      multiple stones (3 of 5 or 60%) compared to solitary renal stones (2 of 15 or
      13.3%). With subsequent extracorporeal shock wave lithotripsy or repeat
      percutaneous nephrolithotomy the stone clearance rate was as high as 92%. At a 2
      to 66-month followup (average 23) no late complications were noted. Radioisotope
      scans available in 10 cases before and after percutaneous nephrolithotomy
      revealed unchanged differential function and evidence of significant renal scars
      in only 1. CONCLUSIONS: Percutaneous nephrolithotomy is a suitable and safe
      procedure for treating renal stones in children.

PMID- 9258206
TI  - Urolithiasis in the exstrophy-epispadias complex.
AB  - PURPOSE: We sought to determine the incidence of urolithiasis in patients with
      the exstrophy-epispadias complex, associated risk factors and guidelines for the
      proper clinical management of this problem. MATERIALS AND METHODS: We
      retrospectively reviewed the chart and x-rays of 530 patients with the exstrophy
      epispadias complex treated at our institution. RESULTS: Stones formed in 77 of
      the 530 patients (15%), including 16% of those with classic exstrophy, 25% of
      those with cloacal exstrophy and 3% of those with epispadias. White and male
      individuals were most commonly affected. Most calculi formed in the bladder,
      whether native or augmented by enterocystoplasty. Standard techniques were
      successful for stone removal. Most calculi consisted of calcium apatite, calcium
      oxalate monohydrate or magnesium ammonium phosphate, usually in combination with
      at least 1 other element. The risk of stone formation was associated with
      augmentation cystoplasty (p < 0.001) and a bladder neck procedure to increase
      outlet resistance (p < 0.001). Other risk factors included urinary tract
      infection, foreign bodies, vesicoureteral reflux and urinary stasis but not
      acidosis or immobilization. Stones recurred in 30 patients (39%), including equal
      numbers of those treated with open and closed techniques, and recurrence was
      associated with urinary tract infection or struvite composition (p < 0.05). Serum
      calcium abnormalities were not present in any patient, including those with
      metabolic acidosis or prolonged immobilization. Urinary chemistry studies were
      incomplete or unavailable. CONCLUSIONS: These data suggest that urolithiasis in
      the exstrophy-epispadias complex is related to risk factors associated with
      surgical reconstruction of this condition. The role of metabolic abnormalities
      that may predispose to urolithiasis is unknown but under investigation. Standard
      treatment is effective but stone recurrence remains a significant problem. Urine
      chemistry data may provide information to help minimize stone development in this
      patient population.

PMID- 9258208
TI  - Fat embolism with the use of intraosseous infusion during cardiopulmonary
      resuscitation.
AB  - The objective of this prospective study was to assess the incidence and magnitude
      of fat emboli after cardiopulmonary resuscitation and intraosseous infusions. An
      animal laboratory at a university center was used to study 33 mixed-breed
      piglets. The piglets underwent hypoxic cardiac arrest followed by chest
      compressions and mechanical ventilation for a minimum of 30 minutes. The animals
      were divided in groups: group 1 (n = 5), which had no intraosseous cannulas,
      group 2 (n = 6), which had intraosseous cannulas with infusion, groups 3 (n = 6),
      4 (n = 6), and 5 (n = 8), which had intraosseous cannulas with infusion of
      epinephrine, normal saline, and sodium bicarbonate respectively, and group 6 (n =
      2), which was a sham group with no intraosseous cannulas and no cardiopulmonary
      resuscitation. At cessation of cardiopulmonary resuscitation, representative lung
      samples were collected from upper and lower lobes of each lung and observed for
      fat globules and bone marrow elements. Fat globules were seen in the
      peribronchial blood vessels and intravascular areas throughout all lung fields of
      groups 1 through 5. There was no difference in appearance or distribution of fat
      globules among the 5 treatment groups. Analysis of variance showed no statistical
      significance (P < 0.05) within or among groups 1 through 5. The use of the
      intraosseous cannula for infusion of emergency drugs and fluids did not increase
      the magnitude of fat embolization over cardiopulmonary resuscitation alone in
      this animal model. The benefits of using this procedure in critically ill
      children as a means of rapid vascular access for resuscitation is well
      established. However, the risk of fat embolism in this population needs further
      study.

PMID- 9258207
TI  - Indomethacin attenuates the renal actions of atrial natriuretic factor in dogs
      with chronic heart failure.
AB  - The interaction between renal prostaglandins and atrial natriuretic factor (ANF)
      for the regulation of renal hemodynamic and excretory function was examined in
      conscious dogs with arteriovenous fistula and chronic compensated high-output
      heart failure (n = 6). After two control clearance periods, 100 ng/kg/min ANF was
      administered for the duration of the study. After two clearance periods with ANF
      infusions, 10 mg/kg indomethacin intravenous bolus was given, and three
      additional clearance periods were obtained. Atrial natriuretic factor alone
      increased sodium excretion from a baseline of 25 +/- 7 microEq/min to 158 +/- 24
      microEq/min (P < 0.05), whereas creatinine clearance was elevated by 9 mL/min (P
      < 0.05). Indomethacin reduced ANF-induced sodium excretion and creatinine
      clearance by 75% (P < 0.05) and 35% (P < 0.05), respectively. In a time control
      series in dogs with arteriovenous fistula (n = 4), indomethacin vehicle did not
      alter ANF-induced natriuresis or renal hemodynamic function. These results
      suggest a modulatory role of the prostaglandins on the renal response to ANF
      infusions in this canine model of compensated heart failure.

PMID- 9258209
TI  - The effect of nonsteroidal antiinflammatory drugs on electrolyte homeostasis and
      blood pressure in young and elderly persons with and without renal insufficiency.

PMID- 9258210
TI  - Nucleoside-nucleotide-free diet suppresses cytokine production and contact
      sensitivity responses in rats with trinitrobenzene sulphonic acid-induced
      colitis.
AB  - We examined the effects of dietary nucleoside-nucleotide mixture on synthesis of
      inflammatory cytokines, interleukin-8 and tumor necrosis factor-alpha, in
      sensitized and nonsensitized colitic rats. Sensitized and nonsensitized colitic
      rats that were fed a nucleoside-nucleotide mixture had greater colonic weight and
      macroscopic and microscopic damage scores than nucleoside-nucleotide-free
      sensitized and nonsensitized colitic rats. Increased colonic tumor necrosis
      factor-alpha and interleukin-8 concentrations were associated with increased
      colonic inflammation and ulceration in the nucleoside-nucleotide mixture-fed
      group. There was also increased ear thickness in the nucleoside-nucleotide
      mixture-fed sensitized and nonsensitized colitic rats, which correlated highly
      with increased tumor necrosis factor-alpha and interleukin-8 levels in the ear
      lobes. Nucleoside-nucleotide-free diets may suppress cytokine secretion, thereby
      reducing colonic damage and contact sensitivity responses in colitic rats.

PMID- 9258211
TI  - Amiodarone-induced thyrotoxicosis.

PMID- 9258212
TI  - The true cost of bone marrow transplantation.
AB  - Bone marrow transplantation is an example of a highly technical therapy that
      offers hope to patients with bone marrow failure or various malignancies. Bone
      marrow transplantation is much more costly "up-front" but perhaps not more costly
      long-term than alternative therapies. Although economic analyses appear
      relatively simple, interpretation and use can be problematic. Several economic
      analyses have identified complications that occur frequently and affect the
      reported cost-effectiveness of high-dose chemotherapy. Efforts to reduce the cost
      of bone marrow transplantation have focused on new strategies to more effectively
      control these complications. The introduction of new technologies to speed
      engraftment, to improve patient selection methods, and the shifting of care to
      outpatient settings all have resulted in significant reductions in duration of
      hospital stay, treatment-related mortality, and costs. More studies of long-term
      outcomes are needed for transplant and nontransplant treatment options to guide
      present and future applications of this treatment option.

PMID- 9258213
TI  - Pure red cell aplasia associated with hepatitis C infection.
AB  - We report the case of a 34-year-old woman with recurrent pure red cell aplasia
      and evidence of hepatitis B and C infection. Review of the English literature
      identified 19 prior cases in which pure red cell aplasia was associated with
      hepatitis. This case is the first in which serologic evidence of hepatitis C
      infection was documented. This patient also had porphyria cutanea tarda and
      marked hepatic siderosis but no active hepatitis or cirrhosis. Treatment with
      cyclophosphamide and prednisone produced complete remission of the pure red cell
      aplasia. Erythroid colony formation (colony-forming unit-erythroid and erythroid
      burst-forming unit) was reduced in cultures of bone marrow obtained during
      relapse but was normal in remission marrow. However, addition of the patient
      serum, whether collected during relapse or remission, inhibited erythroid colony
      formation by her bone marrow. These observations, and the known extrahepatic
      immunologic manifestations of hepatitis C infection, suggest that the pure red
      cell aplasia occurred because of autoimmune mechanism provoked by the infection.

PMID- 9258215
TI  - Acute myocardial infarction after intravenous radiographic contrast medium.
AB  - Acute myocardial infarction after the use of intravenous radiographic contrast
      medium (RCM) is rare. There is only one reported case in the literature; this is
      the second case. A 65-year-old woman complained of pain in the right
      costovertebral area, and abdominal ultrasonography showed hydronephrosis. She had
      insulin-dependent diabetes and hypertension. Intravenous pyelogram, using
      renographin, was performed. Within 5 minutes, she felt bad and became hypotensive
      and diaphoretic. Laboratory studies and electrocardiography confirmed the
      diagnosis of acute myocardial infarction. Generally, elderly and diabetic
      patients with abnormal renal function are considered to be at high risk for
      adverse reactions to RCM. Renal function was normal. It has also been reported
      that high R osmolality RCM such as renographin, is associated with a greater risk
      of adverse reactions compared with the use of low-osmolar RCM. This case should
      raise awareness regarding acute myocardial infarction as a complication after the
      use of intravenous RCM.

PMID- 9258214
TI  - Pityriasis rubra pilaris: an unusual cutaneous complication of AIDS.
AB  - Pityriasis rubra pilaris is an uncommon hyperkeratotic, papulosquamous disorder
      that has been reported in patients infected by HIV. We recount a case of
      pityriasis rubra pilaris in an HIV-seropositive man. A 36-year-old man with a
      history of ulcerative colitis and recurrent otitis externa had diffuse psoriaform
      erythroderma. He was treated initially with methotrexate and isoretinoin without
      clinical improvement. Skin examination showed large, erythematous, orange, scaly
      patches on the upper extremities and thickening of the nail beds. The palms and
      soles were hyperkeratotic. Skin biopsy revealed changes that were consistent with
      pityriasis rubra pilaris. Six months before the onset of symptoms, results of an
      enzyme-linked immunosorbent assay (ELISA) and Western Blot assay for HIV were
      negative. Six months after symptoms, results of repeat enzyme-linked
      immunosorbent assay and Western blots for HIV were positive (CD4+ T-cell count =
      200 cells/ mm3). Clinical course had been complicated by episodes of
      Staphylococcus aureus bacteremia, mucocutaneous candidiasis, and development of
      localized squamous cell carcinoma of the skin. The increased severity of
      pityriasis rubra pilaris should prompt clinicians to consider coinfection with
      HIV in patients who have disease that is refractory to treatment. Clinicians also
      should remain vigilant for the development of squamous cell carcinoma.

PMID- 9258216
TI  - Metastatic breast cancer masquerading as sarcoidosis.
AB  - Malignancies can cause mediastinal and hilar lymphadenopathy that is easily
      mistaken for sarcoidosis. We report a patient with breast cancer who initially
      had respiratory symptoms and thoracic lymphadenopathy. Despite the rarity of
      breast cancer manifesting in this way, the importance of obtaining histologic
      confirmation of suspected sarcoidosis is stressed.

PMID- 9258217
TI  - A long-term dose-response study of mitomycin in glaucoma filtration surgery.
AB  - OBJECTIVE: To establish the long-term, dose-response relationship between the
      concentration of and duration of exposure to mitomycin to a decrease in
      intraocular pressure (IOP) and fewer complications. METHODS: We performed a
      prospective double-masked, placebo-controlled, 1-year study evaluating the
      decrease in IOP and fewer complications of fornix-based trabeculectomy surgery in
      300 eyes equally divided among therapy with placebo; mitomycin, 0.2 mg/ mL,
      applied for 2 minutes; mitomycin, 0.4 mg/mL, applied for 4 minutes; or mitomycin,
      0.4 mg/mL, applied for 2 minutes. All of the eyes had vertical and horizontal cup
      disc ratios greater than 0.7. RESULTS: We observed significant treatment-related
      differences in IOP, with a decrease in IOP in all 3 mitomycin-treated groups for
      all of the times beyond 1 month. The number of eyes achieving strict IOP control
      and the development of cataract suggest a possible dose-response effect for
      concentration and time of exposure. Progressive lens opacification was the most
      frequent complication in 54 eyes (18.1%). The incidence of progressive lens
      changes markedly increased in subjects receiving 4 minutes of mitomycin therapy.
      Cataract formation was unrelated to IOP. Other complications were rare. Macular
      folds developed in 6 patients, with visual acuity returning to better than 20/40
      in all but 1 patient. CONCLUSIONS: A possible dose-response relationship seemed
      to exist between the concentration of and duration of exposure to mitomycin.
      Length of exposure seems to be more important than concentration. The benefits of
      additional decreases in IOP must be weighed against the potential for increases
      in the risk of complications.

PMID- 9258218
TI  - Effect of timolol on the diurnal intraocular pressure in exfoliation and primary
      open-angle glaucoma.
AB  - OBJECTIVE: To describe and compare the diurnal intraocular pressure (IOP)
      variation in patients with exfoliation glaucoma (EXG) and primary open-angle
      glaucoma (POAG) who were treated with a solution of timolol maleate (0.5%) twice
      daily. DESIGN: Consecutive Greek patients who were newly diagnosed as having EXG
      or POAG were prospectively investigated; they underwent 24-hour diurnal IOP
      measurements first without therapy and then 6 months afterward while they were
      being treated with timolol maleate (0.5%). After matching for age, 38 pairs of
      patients with these 2 types of glaucoma were compared. RESULTS: Untreated
      patients with EXG had significantly higher IOP values for all time points
      assessed and a greater mean range of IOPs (11.8 mm Hg for EXG vs 7.6 mm Hg for
      POAG; P < or = .001). Following therapy with timolol maleate (0.5%) given twice
      daily, patients with EXG had higher IOP values for the measurements that were
      obtained at 6 and 10 AM, 10 PM, and 2 AM, a higher mean range of IOPs (7.0 mm Hg
      for EXG vs 5.6 mm Hg for POAG; P = .03), and a higher maximum IOP (mean, 24.9 mm
      Hg for EXG vs 20.9 mm Hg for POAG; P = .003). The reduction of the range of
      diurnal variation of IOP was more pronounced in patients with EXG than in
      patients with POAG (40% vs 26%; P = .04). Twenty-two (58%) of 38 patients with
      EXG and 20 (53%) of 38 patients with POAG had peak IOP values that were found
      outside office hours. Only 5 (13%) of the patients with EXG exhibited an IOP of
      18 mm Hg or less at all time points compared with 12 (32%) of the patients with
      POAG (P = .05). CONCLUSION: Despite a greater initial IOP reduction in the
      patients with EXG treated with timolol, a higher IOP and significant fluctuation
      in the diurnal curve of IOP during the time in which patients received therapy
      still characterized EXG from POAG.

PMID- 9258219
TI  - Effect of cataract and pupil size on image quality with confocal scanning laser
      ophthalmoscopy.
AB  - OBJECTIVE: To determine the effect of pupil size and cataract on the
      reproducibility and image quality obtained with confocal scanning laser
      ophthalmoscopy. METHODS: Three image series were obtained with a confocal
      scanning laser ophthalmoscope (Heidelberg Retina Tomograph, Heidelberg, Germany)
      before and after pupillary dilation in each of 39 subjects (8 normal subjects, 5
      glaucoma suspects, and 26 patients with glaucoma). The cataract density was
      measured with both a lens opacity meter and the Lens Opacities Classification
      System III system. The image quality of each image series was subjectively scored
      on a scale of 0 (poor) to 9 (high) by 2 independent observers who were unaware of
      the cataract density and pupil size during image acquisition. The image quality
      and reproducibility were objectively evaluated using the SD of the mean
      topography image of each subject. RESULTS: The mean pupil diameter in all
      subjects before and after dilation was 2.5 +/- 0.8 mm and 5.8 +/- 1.4 mm,
      respectively. After pupillary dilation, both the mean image quality score and
      mean SD of the mean topography image improved (from 4.5 +/- 3.5 to 7.4 +/- 2.3
      and from 48.6 +/- 18.8 microns to 35.6 +/- 15.5 microns, respectively). The
      quality score of the images that were obtained before pupillary dilation was
      associated with the pupil size and density of nuclear and posterior subcapsular
      cataracts. The SD of the mean topography images that were obtained before
      pupillary dilation increased with a decreasing pupil size (P = .003) and an
      increasing density of the nuclear (P < .03), cortical (P = .02), and posterior
      subcapsular (P = .002) opacity. CONCLUSIONS: Although pupillary dilation improved
      the image quality in most subjects, the improvement was sometimes small. Those
      subjects with small undilated pupils and/or cataracts may benefit most from
      pupillary dilation.

PMID- 9258220
TI  - Submacular surgery for subfoveal choroidal neovascular membranes in patients with
      presumed ocular histoplasmosis.
AB  - OBJECTIVE: To determine the visual results, recurrence rates, and postoperative
      complications of surgical removal of subfoveal choroidal neovascularization (CNV)
      in patients with the presumed ocular histoplasmosis syndrome. DESIGN: A
      consecutive surgical series of 63 eyes of 62 patients with subfoveal CNV and the
      presumed ocular histoplasmosis syndrome with longer than 6 months of follow-up.
      SETTING: Tertiary care university medical center. METHODS: Patients underwent
      surgical removal of subfoveal CNV using vitreoretinal surgical techniques. The
      anatomical and functional results of surgery were analyzed. RESULTS: The median
      age of the patients was 42 years (range, 16-68 years), and the median follow-up
      time was 24 months (range, 6-48 months). Visual acuity improved by 2 or more
      Snellen lines in 22 (35%) of the 63 eyes, was unchanged in 28 (44%) of the eyes,
      and worsened in 13 (21%) of the eyes. Eleven (17%) of the 63 eyes improved to a
      visual acuity of 20/50 or better. Eyes with an initial visual acuity of 20/200 or
      worse had a better prognosis for improved vision (ie, 26 [41%] of the eyes) than
      those with an initial visual acuity of 20/100 or better (ie, 5 [8%] of the eyes).
      Recurrence of the subfoveal CNV occurred in 24 (38%) of the 63 eyes and was more
      common in those eyes that received preoperative laser photocoagulation (ie, 15
      [47%] of the eyes). The median time to recurrence was 5 months after surgery.
      Post-operative complications included macular striae in 4 (6%) of the 63 eyes,
      rhegmatogenous retinal detachment in 2 (3%) of the eyes, retinal tear in 1 (1.6%)
      of the eyes, and progression of cataract in 19 (30%) of the eyes. CONCLUSIONS:
      Surgical excision of subfoveal CNV may be an effective therapeutic modality in
      patients with the presumed ocular histoplasmosis syndrome that offers the
      possibility of improving central vision in many patients. Factors possibly
      associated with a favorable visual prognosis include younger patient age and the
      absence of previous laser photocoagulation.

PMID- 9258221
TI  - Photographic and angiographic characterization of the retina of Kenyan children
      with severe malaria.
AB  - OBJECTIVE: To investigate retinal lesions in children with severe falciparum
      malaria. METHODS: Color photography and fluorescein angiography were performed in
      consecutive children admitted to a pediatric high-dependency unit in Kenya during
      1 malaria season. The presence and category of retinal lesion was compared with
      disease severity, clinical outcome, anemia, lactic acidosis, and parasite count.
      RESULTS: Twenty-six patients with cerebral malaria and 14 patients who were
      prostrate were studied. Thirty-one of the patients had clinical features of
      ocular disease, including round, flame-shaped, and white-centered hemorrhages;
      peripheral and foveal retinal opacification; peripheral vascular occlusion;
      venous dilation; disc edema with hyperemia; and arterial pulsatility. Of 8
      patients with retinal opacification, only 2 showed small, infrequent zones of
      capillary nonperfusion on fluorescein angiography; the leakage of dye at sites of
      opacification was not seen. Retinal opacification was significantly associated
      with a higher parasite count (P < .02). White-centered hemorrhages were
      significantly associated with a higher parasite count (P < .05), severe disease
      (p < .05), and severe anemia (P < .02). CONCLUSIONS: The blood-retina barrier and
      retinal vascular flow remain substantially normal despite widespread pathological
      features. Retinal features in children with severe malaria are consistent with
      cellular hypoxia, nutritional deficiency, or both rather than with vascular
      occlusion; they support the concept of metabolic steal by parasites.

PMID- 9258222
TI  - Unifocal helioid choroiditis.
AB  - OBJECTIVE: To report a previously undescribed clinical entity involving an
      unusual inflammatory lesion of the choroid. PATIENTS: Six young, healthy patients
      experienced acute unilateral visual loss secondary to unifocal choroiditis in the
      macula. RESULTS: All patients exhibited a solitary, elevated, yellow-white active
      focus of choroiditis with overlying subretinal fluid and in some cases subretinal
      hemorrhaging. The lesions were approximately 1 disc diameter in size and, on
      follow-up, showed minimal growth, then gradual resolution of the subretinal
      fluid. No other signs of ocular inflammation were noted, except in 1 patient who
      had anterior chamber and vitreous inflammation. In the 3 patients with prolonged
      follow-up, elevated white plaquelike lesions persisted with little change over
      time. Relapses were seen, and some permanent visual loss occurred in 1 of the 3
      patients. Systemic evaluations revealed no definitive etiology. CONCLUSIONS: To
      our knowledge, these patients exhibit an undescribed clinical entity, separable
      from previously established choroidal disorders. The cause of the lesions remains
      uncertain. We call this entity "unifocal helioid choroiditis."

PMID- 9258223
TI  - Uveal melanoma. Growth rate and prognosis.
AB  - OBJECTIVE: To study in vivo tumor growth rates, doubling times, and the
      association of these parameters with local tumor control and melanoma-related
      mortality. METHODS: We retrospectively reviewed uveal melanomas with documented
      growth on serial evaluations before treatment. The tumor dimensions were based on
      clinical measurements for tumor diameters and quantitative echography to
      determine tumor thickness. One hundred forty-five patients met study criteria.
      All tumors were initially measured by the same observer with the same techniques,
      and, in 133 cases, serial observations and treatment were performed at our
      institution. RESULTS: Tumor-doubling time estimates were log normally
      distributed, with a median of 1.4 years. Those 13 patients in whom metastases
      developed tended to have more rapid tumor growth rates. Iodine 125 brachytherapy
      failed in 8 patients with more rapidly growing tumors. CONCLUSIONS: Faster
      growing tumors appear to be more likely to develop early metastases and have
      failure of local radiation control.

PMID- 9258224
TI  - Elucidation of restrictive motility in high myopia by magnetic resonance imaging.
AB  - OBJECTIVE: To elucidate the cause of an acquired, restrictive motility disorder
      in patients with high myopia. METHODS: Magnetic resonance imaging (MRI) scans
      were obtained from 37 patients with high myopia (axial length of globe, 29.4 mm;
      refractive error, > -15 diopters). Additional dynamic MRI scans were obtained in
      which the patient fixated in various positions with the less restricted eye for
      50 seconds. Twenty normal orbits were studied in control MRI scans. RESULTS: The
      path of the lateral rectus, in the anterior and midorbital regions, was displaced
      downward an average of 3.4 mm in 13 patients with typical esotropia and
      hypotropia. This mislocation reduces abducting torque of the lateral rectus and
      creates depressing and extorting moments. The muscle insertions were normal,
      except where previous strabismus surgery relocated them. Contact between the
      enlarged globe and the bones of the orbital apices that would cause esotropia was
      not observed. CONCLUSIONS: This eye muscle abnormality in patients with high
      myopia is another strabismus syndrome related to abnormalities of orbital
      connective tissues and muscle paths. Orbital MRI scans may be useful before
      strabismus surgery in patients with high myopia. If an abnormal lateral rectus
      path is found, surgery should be directed to normalize it. Magnetic resonance
      imaging morphometry in high myopia may give additional information on orbital
      anatomy and biomechanical mechanisms of strabismus.

PMID- 9258225
TI  - Do intact viral particles survive excimer laser ablation?
AB  - OBJECTIVE: To determine if intact and potentially infectious viral particles can
      withstand excimer laser ablation and possibly pose a health hazard to medical
      personnel. METHODS: Excimer laser ablation of fibroblasts infected with
      attenuated varicella-zoster virus was performed. The laser plume was collected
      for polymerase chain reaction analysis and viral culture. RESULTS: While viral
      DNA was detected in the material trapped from the laser plume, live virus could
      not be demonstrated to have survived ablation. CONCLUSIONS: Attenuated varicella
      zoster virus does not seem to survive excimer laser ablation. However, we
      recommend the use of safety precautions such as wearing a mask during the
      procedure. Further research is necessary to determine if other viruses could
      possibly remain infectious despite exposure to excimer laser radiation.

PMID- 9258226
TI  - TUNEL-positive ganglion cells in human primary open-angle glaucoma.
AB  - OBJECTIVE: To determine whether retinal ganglion cell death in primary open-angle
      glaucoma occurs by apoptosis. METHODS: Eighteen eyes of 17 subjects with
      documented primary open-angle glaucoma were compared with 21 control eyes that
      were group matched for age, race, and sex. Staging of glaucoma severity was
      performed by histologic optic nerve evaluation. Fixed, paraffin-embedded retinal
      sections were assayed by the TUNEL (terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate (UTP)-biotin nick end-labeling) method to
      detect the internucleosomal DNA fragmentation that is characteristic of
      apoptosis. RESULTS: A positive TUNEL reaction was observed among ganglion layer
      cells in 10 of 18 cases with glaucoma, compared with 1 of 11 control cases
      without confounding systemic disease (5 control eyes were excluded owing to
      artifactual staining and 4 eyes had confounding systemic disease). Sections
      containing more than 250,000 cells in the ganglion cell layer were examined in
      cases and controls. The frequency of TUNEL-positive cells in the ganglion cell
      layer in cases with glaucoma was 1.76 per 10,000, or 15.2 times greater than the
      control frequency from individuals without confounding disease (P < .001; 95% CI,
      2.46-623). Eyes without glaucoma from subjects with diabetes and amyotrophic
      lateral sclerosis showed more positive cells than other controls. CONCLUSION:
      Apoptosis seems to be a mechanism of cell death in human eyes with primary open
      angle glaucoma.

PMID- 9258228
TI  - Distribution of intraocular pressure. The Barbados Eye Study.
AB  - OBJECTIVE: To provide data on the distribution of intraocular pressure (IOP) in a
      predominantly black population, which has a high prevalence of open-angle
      glaucoma. DESIGN: Population-based prevalence study. SETTING AND PARTICIPANTS:
      Participants (N = 4601) (age range, 40-84 years) who had undergone applanation
      tonometry measurements in the Barbados Eye Study. Self-reported race was 93%
      black, 4% mixed (black and white), and 3% white or other. DATA COLLECTION: A
      standardized protocol included applanation tonometry and other ocular
      measurements, fundus photography, demographic data, and an interview. MAIN
      OUTCOME MEASURES: The average of 3 IOP measurements at the Barbados Eye Study
      visit was used to compare IOP by self-reported race. Descriptive data on IOP by
      age, sex, glaucoma status, and cup-disc ratio were examined in the black
      population. RESULTS: The IOP was highest in the population of African origin. The
      mean (+/-SD) IOP values for black, mixed, and white participants were 18.7 +/-
      5.2, 18.2 +/- 3.8, and 16.5 +/- 3.0 mm Hg, respectively. An IOP greater than 21
      mm Hg was present in 18.4%, 13.6%, and 4.6% of the black, mixed, and white
      participants, respectively. In analyses that were adjusted for age, sex, and
      glaucoma status, such values were 5 times as likely in black than white
      participants and 3.5 times as likely in mixed race participants (P < .01). Among
      the black participants, the mean IOP increased approximately 1 mm Hg for every
      increase in 10 years of age. After excluding persons with any type of glaucoma,
      suspected glaucoma, or a history of glaucoma treatment, women had significantly
      (P < .01) higher IOP values; however, no significant IOP trends by sex were
      evident in the group with glaucoma. The IOP was also positively associated (P <
      .05) with vertical cup-disc ratios. After 2 visits, the IOP remained 21 mm Hg or
      less in 21% of the persons with glaucoma vs 64% of those without glaucoma.
      CONCLUSIONS: In the black participants, the IOP was higher than in the white
      participants. The IOP was also associated with age and cup-disc ratios. The
      results showed that open-angle glaucoma and a high IOP alone have a different
      distribution by sex; although open-angle glaucoma was more frequent in men,
      ocular hypertension was more frequent in women. These data have implications for
      the detection and causation of open-angle glaucoma in this high-risk population.

PMID- 9258227
TI  - An aldose reductase inhibitor and aminoguanidine prevent vascular endothelial
      growth factor expression in rats with long-term galactosemia.
AB  - OBJECTIVE: To study the effects of an aldose reductase inhibitor (ARI-509, Wyeth
      Ayerst, Princeton, NJ) and aminoguanidine (AMG), agents that have been reported
      to prevent or delay diabetic retinopathy, on retinal vascular abnormalities and
      the immunocytochemical expression in the retina of vascular endothelial growth
      factor (VEGF) in rats maintained for up to 2 years on a 50% galactose diet.
      METHODS: Albino rats were placed on a control diet, a diet containing 50%
      galactose, or the 50% galactose diet containing either ARI-509 or AMG. Treatment
      with ARI-509 or AMG was initiated at the beginning of the experiment or after 12
      months of galactose feeding. After 22 to 24 months, the rats were killed and the
      retinal vasculature from half of one eye was isolated by trypsin-elastase
      digestion for semiquantitative evaluation of retinal vascular lesions. The other
      half of the retina was prepared for immunocytochemistry and stained for the
      presence of VEGF, factor VIII, vimentin, and glial fibrillary acidic protein. Red
      blood cells, sciatic nerves, and a portion of the retina from the second eye were
      assayed for glucose, galactose, fructose, sorbitol, galactitol, and myo-inositol.
      Red blood cells were also assayed for galactosylated hemoglobin. RESULTS:
      Galactose-fed animals developed a vascular retinopathy characterized by severe
      cellular loss in the retinal capillaries and intensification of periodic acid
      Schiff staining of the vascular basement membranes. Some animals also displayed
      dilation and hypercellularity of vessels in the posterior retina. These changes
      were substantially reduced in animals receiving ARI-509 from the beginning of the
      galactose diet, but were unaffected in all of the other treatment groups. None of
      the rats receiving ARI-509 or AMG treatment, whether initiated from the onset or
      after 12 months of galactosemia, demonstrated VEGF immunoreactivity. With the
      exception of the animals receiving ARI-509 from the beginning of the experiment,
      all of the galactose-fed animals developed dense cataracts within 6 weeks of the
      beginning of the galactose diet. Galactitol levels in animals receiving ARI-509
      were 86% to 93% lower in red blood cells, retina, and sciatic nerve than those in
      the other galactose-fed groups. CONCLUSIONS: Although ARI-509 and AMG have
      different abilities to delay or prevent the diabetic-like retinopathy in
      galactosemic rats, even when substantial retinal microvascular acellularity
      occurs, both drugs prevent the immunocytochemical expression of VEGF. These
      results suggest that factors other than hypoxia may be responsible for VEGF
      expression in the retina, and that aldose reductase inhibitors and AMG have
      potential roles in preventing such expression and, thus, perhaps preventing
      retinal neovascularization.

PMID- 9258229
TI  - Central cloudy corneal dystrophy of Francois. A clinicopathologic study.
AB  - Central cloudy corneal dystrophy of Francois was first described in 1955 by J.
      Francois; its pathophysiology remains unknown. An 80-year-old woman with
      bilateral central cloudy corneal dystrophy of Francois was examined after having
      undergone a combined penetrating keratoplasty and cataract extraction. The
      corneal button was obtained. Light microscopy revealed stromal staining for acid
      mucopolysaccharide. Transmission electron microscopy revealed extracellular
      vacuoles, some of which had fibrillogranular material and electron-dense
      deposits. Fibrillogranular material was present in and around some keratocytes.
      Numerous endothelial vacuoles contained light-staining fibrillogranular material
      and round electron-dense granules. Our findings suggest that the opacities in
      patients with central cloudy corneal dystrophy of Francois are due to the
      extracellular accumulation of mucopolysaccharide and lipidlike material. Further
      studies are needed to elucidate the nature of these deposits.

PMID- 9258230
TI  - Exfoliation syndrome in a 17-year-old girl.
AB  - A 17-year-old girl with unilateral congenital glaucoma who had undergone
      trabeculectomy and peripheral iridectomy in infancy developed apparent
      exfoliation syndrome (XFS) in the eye that underwent the surgical procedures. A
      conjunctival biopsy was performed and the specimen was fixed in 2.5%
      glutaraldehyde, embedded in epoxy resin (Epon-Araldite, Electron Microscopy
      Sciences, Fort Washington, Pa), and processed for routine electron microscopy and
      immunostaining for elastin. Results of ultrastructural study showed scattered
      fibrillar aggregates compatible with those of XFS in an older adult, differing
      chiefly in sparsity of granular interfibrillar matrix. The XFS fibers were
      closely associated with elastic fibers and microfibrils. Elastosis of the actinic
      aging type was somewhat greater than expected for age. To our knowledge, this is
      the youngest patient described with characteristic ocular findings of XFS to
      date, supporting others who have suggested an association between iris surgery in
      youth and early onset XFS. Electron microscopy was essential in ruling out the
      possibility of a clinically similar entity caused by ultrastructurally different
      material.

PMID- 9258231
TI  - Adjunctive use of mitomycin in filtration surgery. Is it worth the risk?

PMID- 9258232
TI  - Submacular surgery. New information, more questions.

PMID- 9258233
TI  - Barriers to prevention of vision loss caused by diabetic retinopathy.

PMID- 9258234
TI  - Filtering bleb infection as a complication of orthokeratology.

PMID- 9258235
TI  - Central retinal vein occlusion in a young child with cyanotic heart disease.

PMID- 9258237
TI  - Late microhyphema associated with a cataract incision.

PMID- 9258236
TI  - Sclerochoroidal calcification in calcium pyrophosphate dihydrate deposition
      disease (pseudogout)

PMID- 9258238
TI  - Idiopathic sclerochoroidal calcification in a 41-year-old woman.

PMID- 9258239
TI  - Motion stereoscopic vision, the Pulfrich phenomenon, and baseball hitting.

PMID- 9258240
TI  - Hemorrhage into an intraorbital pseudocyst.

PMID- 9258241
TI  - Subperiosteal orbital hemorrhage from retrobulbar injection resulting in
      blindness.

PMID- 9258242
TI  - Diagnosis of occult lenticular nuclear sclerosis using the Hruby lens.

PMID- 9258243
TI  - Monovision therapy in patients with presbyopia and binocular diplopia.

PMID- 9258244
TI  - The Norton Lecture: a review of the oligodendrocyte in the multiple sclerosis
      lesion.
AB  - The mechanisms involved in the elimination of oligodendrocytes and myelin from
      the demyelinated plaque of multiple sclerosis (MS) are inextricably intertwined
      and yet most investigations tend to consider them separately. This short review
      revisits the problem of oligodendrocyte pathology in MS and attempts to put the
      topic into perspective by examining the numerous immunologically-active molecules
      associated with the oligodendrocyte, some, but not all, cross-reactive with
      myelin. The consensus of opinion is that myelin is the primary target in MS but
      that oligodendrocytes are eventually lost from the lesion. Reappraisal of recent
      and past works brings into focus a possible key role for soluble mediators, in
      particular antibody and the pro-inflammatory cytokine, TNF alpha, in
      oligodendrocyte loss and myelin in MS. Despite extensive neuropathologic
      investigation by a number of laboratories, no evidence has yet been found to
      support the concept that apoptosis might account for oligodendrocyte depletion in
      MS, even though molecules belonging to the apoptotic cascade can be expressed by
      oligodendrocytes in and around lesions. Indeed, abundant evidence has been
      presented to show that oligodendrocytes initially respond to the demyelinating
      insult in MS by proliferating and elaborating new myelin but, no doubt due to the
      relentless progression of inflammatory events, the cells are eventually lost,
      probably via a cytolytic pathway. Strategies to block the progression of CNS
      inflammation in EAE and MS appear to promote the survival of oligodendrocytes and
      to enhance remyelination. Such strategies appear to hold much promise for the MS
      patient.

PMID- 9258245
TI  - Altered thymic endocrine activity along with impairments of peripheral zinc
      metabolism and T-lymphocyte populations are associated with myasthenia gravis: a
      follow-up study.
AB  - Thymic endocrine activity was assessed by a bioassay to determine the basal
      activity of thymulin (TH), a zinc dependent hormone, and its in vitro
      reactivation in two different age groups of patients with myasthenia gravis (MG).
      Before thymectomy, basal TH plasma levels were increased in patients over the age
      of 50 years. Plasma zinc levels were increased in all patients, this increment
      being very high in old patients. One year after thymectomy both TH and zinc
      plasma levels decreased. While zinc plasma levels were within the normal ranges
      for their respective ages, TH levels were lower in young and higher in old
      patients than in age comparable controls. Young patients with MG showed increased
      CD3,DR positive peripheral T-cells as well as lymphocytes with the CD16,CD56
      phenotype. An increment of CD3 positive cells along with CD4 and CD16,CD56
      positive cells were found in older patients. Thymectomy partially affected blood
      lymphocyte representation only in young patients, since CD3,DR T-cells decreased
      one year after surgery. No significant variations in T-cell representation were
      found in old patients after thymectomy. Immunosuppression in thymectomized
      patients did not significantly affected TH and zinc plasma levels. Very high
      levels of TH and the presence of additional alterations in T-lymphocyte subsets
      in old patients suggested that differential age related pathogenetic
      immunological mechanisms might be associated with the disease.

PMID- 9258246
TI  - Distribution of NGF receptors in normal and pathologic human lymphoid tissues.
AB  - To identify nerve growth factor (NGF) target cells in normal and pathologic human
      lymphoid tissues, we have studied the expression of the low-affinity NGF receptor
      (p75LNGFR) and the high-affinity tropomyosin-related kinase NGF receptor (TrkA).
      A RNAse protection assay revealed the expression of trk transcripts in thymus,
      spleen, palatine tonsils and lymph nodes. TrkA immunoreactivity was shown in
      thymic epithelial cells, cryptic tonsillar epithelium and several monocyte
      derived cells including epithelioid and multinucleated Langhans' cells,
      follicular dendritic cells and interdigitated reticular cells. TrkA
      immunoreactivity was rarely observed in normal T- and B-lymphocytes, but was
      intense in lymphoma cells of several B-cell lymphoma subtypes, anaplastic large
      cell lymphomas and Reed-Sternberg cells. Western blot analysis revealed the
      presence of p75LNGFR and of p80Trk and glycosylated Trk isoforms (gp110, gp140).
      p75LNGFR immunoreactivity was detected in epithelial Hassal's bodies, follicular
      dendritic cells, interdigitated reticular cells, periarteriolar macrophages,
      endothelial sinusal cells and nerve endings. The broad expression of NGF
      receptors may be an indicator of neurotrophin activity in lymphoid tissues and
      suggests their implication in inflammatory or lymphoproliferative disorders.

PMID- 9258247
TI  - Induction of thymic hyperplasia and suppression of splenic T cells by lesioning
      of the anterior hypothalamus in aging Wistar rats.
AB  - The effect of destruction of the anterior hypothalamus (AHT) on the immune system
      was examined in rats 4-50 weeks after the treatment. The thymic weight
      significantly increased in the experimental group regardless of age, while a
      significant decrease was observed in the percentage of splenic T cells as well as
      their proliferative response to phytohemagglutinin (PHA). The increase of thymic
      weight was observed as long as 24 weeks and the decrease of splenic T cell number
      was observed as long as 50 weeks after the operation. Hypophysectomy gave rise to
      atrophy of both thymus and spleen, while either adrenalectomy or gonadectomy
      resulted in hypertrophy of both thymus and spleen. The results taken together
      suggest that development and aging of the immune system are under the balance of
      positive and negative signals from AHT.

PMID- 9258248
TI  - HLA-DM polymorphisms do not associate with multiple sclerosis: an association
      study with analysis of myelin basic protein T cell specificity.
AB  - The MHC region on 6p harbors at least one susceptibility gene for multiple
      sclerosis (MS). Within this region, HLA-DM loci are of interest being involved in
      class II antigen processing. We investigated the association of HLA-DM
      polymorphisms with MS. Sixty-three patients with MS and 46 healthy controls from
      continental Italy were typed for HLA-DM polymorphisms and HLA-DRB1 alleles.
      Besides, among the donors characterized for the DM polymorphisms, we considered 6
      MS patients previously studied for the fine specificity of their MBP-specific T
      lymphocyte lines (TLL). The frequencies of allelic variants at the DMA and DMB
      loci were similar between MS patients and controls, even when HLA-DRB1*1501
      positive and negative donors were analyzed separately. Patients with predominant
      responses to different MBP epitopes did not differ for their HLA-DM haplotype
      while patients with predominant responses to the same MBP epitope could present
      different HLA-DM haplotypes. HLA-DM polymorphisms do not associate with MS and
      may not affect specific patterns of T cell responses to MBP.

PMID- 9258249
TI  - Fibrin deposition in the central nervous system correlates with the degree of
      Theiler's murine encephalomyelitis virus-induced demyelinating disease.
AB  - We examined the role of coagulation-fibrinolysis system in Theiler's murine
      encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). The degree of
      fibrin deposition around the vessels in the spinal cord was significantly higher
      in susceptible SJL/J mice on 30 days post intracerebral injection (i.c.) than
      resistant C57BL/6 mice on 30 days post i.c. or mock infected SJL/J mice.
      Treatment with batroxobin (30 BU/kg/day), which is a thrombin-like
      defibrinogenating enzyme, causing a profound degree of afibrinogenemia,
      suppressed clinical signs of TMEV-IDD. Plasma fibrinogen concentration was
      significantly decreased in batroxobin-treated mice. Histologically, though the
      degree of perivascular mononuclear cell infiltration in the spinal cord was not
      suppressed in batroxobin-treated mice compared to saline-treated control mice,
      fibrin deposition was markedly suppressed in batroxobin-treated mice. These
      findings suggest that batroxobin suppresses TMEV-IDD through its defibrination
      effect, and provide evidence that CNS-associated deposition of fibrin and ensuing
      fibrinolysis, together with increased permeability of the blood-brain barrier
      (BBB), are prerequisite events for clinical manifestations of TMEV-IDD.

PMID- 9258250
TI  - T cell response to myelin basic protein in the context of the multiple sclerosis
      associated HLA-DR15 haplotype: peptide binding, immunodominance and effector
      functions of T cells.
AB  - In this study, we evaluated the role of the two functional HLA-DR heterodimers,
      DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR
      alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in
      the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting
      myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our
      results show that both HLA-DR molecules serve as restriction elements for HLA
      DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction
      element, and the epitopes contained in the immunodominant C-terminal region (131
      159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99)
      is recognized in the context of both DR2a and DR2b, but this specificity strongly
      dominates the DR2b-restricted T cell response. Overall, immunodominance in the
      MBP-specific T cell response correlated well with peptide binding to DR2a or
      DR2b, demonstrating that the affinity of MHC-peptide interactions is important
      for shaping the T cell response to this autoantigen. Furthermore, we show that
      binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by
      cathepsin D, a protease abundantly found in endosomal processing compartments,
      and thus contributes to its immunodominance. Surprisingly, the restriction
      element employed by MBP-specific T cell clones influenced the effector function
      (i.e., cytotoxic activity) of T cells irrespective of their peptide fine
      specificity.

PMID- 9258251
TI  - Identification of interleukin-6 producing fibroblastoid cells in cerebrospinal
      fluid from patients with leukemic meningitis.
AB  - Cytokine producing native cells in cerebrospinal fluid (CSF) have not been
      identified. So, we investigated the cytokine producing ability of floating cells
      in CSF from patients with leukemic meningitis. Morphologic study revealed that
      established cell lines were polygonal or elongated in shape and had an abundant
      and irregular branched cytoplasm. Immunocytochemical analysis demonstrated
      positive reactivity with monoclonal anti-fibroblast antibody only. Interleukin-6
      (IL-6) was constitutively produced in vitro by these cell lines; both interleukin
      1 and lipopolysaccharides significantly increased its synthesis. These findings
      imply that these fibroblastoid cells are floating in CSF of patients with
      leukemic meningitis and produce IL-6 in response to various inflammatory
      stimulations in vivo.

PMID- 9258253
TI  - Review of Rett syndrome.

PMID- 9258252
TI  - Beta 2-adrenergic activation enhances interleukin-8 production by human
      monocytes.
AB  - Interleukin-8 (IL-8) is an important cytokine in inflammatory processes by
      functioning as a chemoattractant and as an activator of oxygen metabolism. In the
      present study we demonstrate that beta 2-adrenergic agonists potentiate the
      lipopolysaccharide (LPS) and IL-1 induced production of IL-8 by human monocytes.
      In addition, beta 2-adrenergic activation enhances IL-8 release and mRNA
      expression for IL-8 in the human monocytic cell line U937. beta 2-adrenergic
      activation of these cells also results in enhanced production of the anti
      inflammatory cytokine IL-10. However, IL-10 is not involved in the regulation of
      IL-8 production. The effect of the beta 2-adrenergic agonist on IL-8 production
      is presumably mediated via increased cAMP formation, since it can be mimicked by
      the cAMP analogue dibutyryl-cAMP (db-cAMP). We conclude that enhancement of IL-8
      production is one of the pathways via which beta 2-adrenergic agonists such as
      catecholamines can influence inflammatory responses.

PMID- 9258255
TI  - Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III
      gliomas.
AB  - The grading of glial tumors has traditionally relied on histological assessment,
      but the distinction between grade II and grade III gliomas is still a subject of
      debate. We examined the value of the monoclonal antibody MIB-1 (Ki-67) labeling
      index (LI) in the differentiation between grade II and grade III gliomas by
      either the 1993 WHO grading scheme or the St. Anne-Mayo grading scale. The MIB-1
      Li in the most densely labeled areas from 80 diffuse cerebral hemispheric gliomas
      was determined. The tumors included 16 grade II, 31 grade III and 33 grade IV
      gliomas by the WHO scale. The mean LIs (%) were 0.88 +/- 0.29 for grade II, 8.75
      +/- 1.71 for grade III, and 9.12 +/- 1.55 for grade IV gliomas. Analysis of
      variance indicated a significant difference in mean LIs between grades II and III
      and grades II and IV (p < or = 0.0001), but not between grades III and IV. Seven
      tumors were classified differently by the 2 systems (grade III by WHO, but grade
      2 by St. Anne-Mayo), and all had MIB-1 LI over 3%. Univariate analysis showed
      that MIB-1 LI with a cut-off point at 1.5% was a significant prognostic factor (p
      < or = 0.0005). High tumor grade (WHO, p < or = 0.0002; St. Anne-Mayo, p < or =
      0.0006) and patient age > 50 (p < or = 0.0001) were also significant factors for
      shorter survival. Using Cox Regression Multivariate Analysis, MIB-1 LI > 1.5% was
      a significant independent predictor of shorter disease survival when paired with
      tumor grade (p < or = 0.032), patient age (p < or = 0.0065), or gender (p < or =
      0.0007). We conclude that the MIB-1 immunoreactivity is useful in distinguishing
      grade II from grade III gliomas, and maybe more sensitive in assigning aggressive
      gliomas to grade III than the St. Anne-Mayo grading system.

PMID- 9258254
TI  - Myofibrillar myopathy. III. Abnormal expression of cyclin-dependent kinases and
      nuclear proteins.
AB  - The pathological process in myofibrillar myopathy (MFM) (previously also referred
      to as "desmin storage" or "intermediate filament myopathy") results in
      dissolution of myofibrils, accumulation of products of the degradative process,
      and abnormal ectopic expression of desmin, dystrophin, gelsolin, NCAM, and N
      terminal components of beta-amyloid precursor protein. We now demonstrate that
      the abnormal fiber regions in MFM immunoreact strongly for (a) CDC2 kinase, the
      mitotic kinase that phosphorylates and disassembles intermediate filaments; (b)
      cyclin-dependent kinases CDK2, CDK4, and CDK7, which are involved in regulation
      of the cell cycle; (c) lamin B, which normally supports the inner nuclear
      membrane; and (d) the nuclear matrix associated protein. The normal muscle fiber
      lies in a terminally differentiated state and is refractory to reentry into the
      cell cycle. The abnormal expression of multiple cyclin-dependent kinases in the
      terminally differentiated muscle fiber implies inappropriate activation of
      positive regulators of mitosis and may signal a mitotic catastrophe. The
      dissolution of myofibrils may be due to hyperphosphorylation occurring during
      this event.

PMID- 9258256
TI  - 4-hydroxy-2-nonenal pyrrole adducts in human neurodegenerative disease.
AB  - Increasing age and inheritance of the epsilon 4 allele of apolipoprotein E
      (APOE4) are significant risk factors for sporadic and late onset familial
      Alzheimer disease (AD); however, the mechanisms by which either leads to AD are
      unknown. Numerous studies have associated advancing age with increased indices of
      oxidative challenge to brain, and with still further increased oxidative damage
      to relevant brain regions in AD patients. A major consequence of oxidative damage
      to brain is lipid peroxidation with production of the neurotoxic metabolite 4
      hydroxy-2-nonenal (HNE). HNE reacts with protein to yield several adducts,
      including a pyrrole adduct that forms irreversibly in biological systems.
      Previously, we have shown in a small number of AD and control patients that HNE
      pyrrole adduct antiserum is immunoreactive with neurofibrillary tangles (NFT),
      and that this reactivity was significantly associated with inheritance of APOE4.
      Others have confirmed this pattern of immunoreactivity in AD brain but did not
      observe an association with APOE4. Herein, we have expanded the study group to 19
      AD patients homozygous for APOE4 or APOE3, as well as 30 patients with other
      neurodegenerative diseases, including diffuse Lewy body disease, Pick's disease,
      progressive supranuclear palsy, Parkinson's disease, and human immunodeficiency
      virus-1 encephalitis. HNE pyrrole adduct immunoreactivity on NFT in AD patients
      was strongly associated with APOE4 homozygosity. With the exception of rare
      immunoreactive Pick bodies in one case of Pick's disease, no other structure was
      recognized by HNE pyrrole adduct antiserum in this series of patients. We propose
      that there is a significant difference between the interaction of apoE3 and apoE4
      with lipid peroxidation in the brains of AD patients.

PMID- 9258257
TI  - Adenovirus-mediated wild-type p53 gene transfer and overexpression induces
      apoptosis of human glioma cells independent of endogenous p53 status.
AB  - Mutation or inactivation of the p53 tumor suppression gene is an early alteration
      in the transformation of glial cells to gliomas. To study the effect of exogenous
      wild-type p53 on glioma cell growth, human glioma lines U251 MG, U87 MG and A172
      were infected with an adenovirus vector expressing either wild-type p53 or
      bacterial lacZ. Rapid cell death occurred only in the p53-transduced cell lines
      and was characterized by nuclear condensation, formation of nucleosomal DNA
      ladders, and positive in situ end-labeling of DNA, suggesting that apoptosis had
      been induced. The U87 MG cell line that contains wild-type p53 as evidenced by
      wild-type p53-dependent transcription activity also underwent apoptosis within 2
      to 3 days after infection. These results suggest that the presence of endogenous
      wild-type p53 does not preclude apoptosis by overexpression of exogenous p53.

PMID- 9258258
TI  - Loss of alkaline phosphatase activity in meningiomas: a rapid histochemical
      technique indicating progression-associated deletion of a putative tumor
      suppressor gene on the distal part of the short arm of chromosome 1.
AB  - Apart from defined histomorphologic features, increased Ki-67 indices and various
      numeric and structural chromosome aberrations, meningiomas of the intermediate
      (WHO grade II, atypical meningioma) and anaplastic type (WHO grade III) are
      cytogenetically distinguished from common-type meningiomas (WHO grade I) by
      frequent loss of the distal part of the short arm of one chromosome 1 (1p-),
      which formerly proved to be an independent predictor of shorter recurrence-free
      intervals. Histochemically, loss of alkaline phosphatase activity (ALPL,
      liver/bone/kidney type, EC 3.1.3.1) was another frequent, specific finding in
      meningiomas with signs of dedifferentiation. In a prospective study including 66
      meningiomas, all common-type meningiomas except one case (18/19) were reactive
      for ALPL, whereas 75% (30/39) of intermediate type and all anaplastic meningiomas
      (8/8) showed loss of enzyme activity in large areas of the tumor. Exclusively,
      the ALPL negative phenotype was associated with 1p loss (15/19). Our data suggest
      that ALPL, which is coded as a single copy gene on chromosome 1p36.1-p34, is a
      useful marker enzyme for the loss of a putative regulatory (tumor suppressor)
      gene on chromosome 1p, or that ALPL itself represents a new tumor suppressor gene
      homozygously inactivated in meningiomas.

PMID- 9258259
TI  - DNA damage distribution in the human brain as shown by in situ end labeling; area
      specific differences in aging and Alzheimer disease in the absence of apoptotic
      morphology.
AB  - DNA damage has been proposed to underlie neuronal degeneration in aging and
      Alzheimer disease (AD). To determine the histological distribution of DNA damage,
      in situ end labeling (ISEL) was applied as a marker for DNA breaks on 4
      differentially affected brain areas. Occipital cortex showed considerable
      variation between cortical layers and between patients. Temporal cortex displayed
      little ISEL-labeling in controls, and in AD, surprisingly. In the hippocampus,
      which is strongly affected in AD, many ISEL-positive nuclei and glialike cells
      were found in AD as compared with controls. The hypothalamic supraoptic and
      paraventricular nuclei showed little DNA-damage, whereas the nucleus basalis was
      often, but not always, labeled by ISEL. In contrast to others, no apoptotic
      morphology was observed, only necrotic morphology. Our results in relation to
      postmortem delay indicate that, area dependent, increased DNA vulnerability may
      occur in AD. Furthermore, the distribution of DNA damage in cortex differs from
      that of plaques and tangles, suggesting that these 3 phenomena are, in principle,
      independent. Whether the enhanced level of hippocampal DNA breaks in AD
      underlies, or rather is a consequence of, previous degenerative changes in this
      brain area remains to be established.

PMID- 9258260
TI  - Glutamate transporter alterations in Alzheimer disease are possibly associated
      with abnormal APP expression.
AB  - Recent studies have shown that deficient functioning of glutamate transporters
      (GTs) in Alzheimer disease (AD) might lead to neurodegeneration. The main
      objectives of the present study were to determine which GT subtype is most
      affected in AD and to asses to what extent altered GT function is associated with
      abnormal amyloid precursor protein (APP) expression. While EAAT2-immunoreactivity
      (IR) was decreased in AD frontal cortex, EAAT1- and EAAT3-IR were unaffected;
      mRNA levels for all 3 GTs were not affected. Decreased EAAT2-IR was associated
      with decreased GT activity. EAAT2-IR inversely correlated with EAAT2 mRNA levels,
      suggesting that in AD, GT expression alterations occur due to disturbance at the
      post-transcriptional level. EAAT2-IR was inversely correlated with APP770 mRNA.
      In addition, GT activity directly correlated with APP695 mRNA and total APP
      protein levels, and inversely correlated with APP751/770 mRNA levels. This study
      supports the notion that astroglial EAAT2 is affected in AD and abnormal
      functioning and/or processing of APP might play an important role in this
      process.

PMID- 9258261
TI  - Role of vascular endothelial growth factor in blood-brain barrier breakdown and
      angiogenesis in brain trauma.
AB  - The role of vascular endothelial growth factor (VEGF) in blood-brain barrier
      (BBB) breakdown and angiogenesis, observed previously in the cerebral cortical
      cold-injury model, was investigated. Immunohistochemistry was used to assess BBB
      permeability to plasma fibronectin and to localize VEGF protein in the cortical
      cold-injury model over a period of 10 min to 14 days post-injury. BBB breakdown
      to fibronectin in lesion vessels was observed at 10 min post-injury, was maximal
      between 2 and 4 days and declined gradually thereafter, while occasional
      perilesional vessels remained permeable up to 6 days. Increased VEGF
      immunoreactivtiy occurred later-it was observed in pial vessels after 6 hours
      (h), and persisted up to day 14. Arterioles within the cold lesion showed VEGF
      immunoreactivity at 36 h, thus preceding the onset of endothelial proliferation
      and angiogenesis that occurred from day 3 to day 5. VEGF immunoreactivity was
      also observed in inflammatory cells and astrocytes. These results indicate that
      the immediate breakdown of the BBB in the cold lesion is unrelated to VEGF. The
      presence of mural VEGF in permeable pial vessels and lesional arterioles suggests
      that VEGF is one of several factors that mediates BBB breakdown in this model.
      The association of maximal VEGF immunoreactivity with endothelial proliferation
      and neovascularization suggests that VEGF promotes angiogenesis and repair
      following brain trauma.

PMID- 9258262
TI  - Amyloid beta-protein (A beta) accumulation in the leptomeninges during aging and
      in Alzheimer disease.
AB  - The results of well-characterized two-site enzyme immunoassays showed that the
      crude leptomeninges (consisting of the pia matter, arachnoid matter, and
      leptomeningeal vessels [LV]) from aged control brains and brains affected by
      Alzheimer disease (AD) contain very high levels of amyloid beta-protein (A beta).
      To learn about the source of A beta, we carefully dissected out both
      leptomeninges (LM) and LV under a dissecting microscope and determined the levels
      of soluble A beta in each. The purity of these dissected tissues was confirmed by
      the absence or presence of alpha-smooth muscle actin representing LV by Western
      blotting. Surprisingly, the amounts of A beta in each dissected sample were
      nearly equivalent on a weight basis. In each compartment from aged controls the
      level of A beta 1-42 was comparable to that of A beta 1-40, while in AD brain A
      beta 1-40 was a predominant species in both LM and LV. In some cases careful
      immunocytochemical examination revealed the presence of A beta deposits that were
      immunolabeled by several A beta monoclonal antibodies in leptomeningeal layers
      (most often in the arachnoid matter). The extent of A beta deposition in LM
      appeared to be much less than that explained by the soluble A beta levels,
      suggesting that immunocytochemically undetectable A beta can accumulate in LM.
      These observations indicate that leptomeninges are a large reservoir of A beta in
      normal aged individuals and in AD patients.

PMID- 9258263
TI  - Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates
      with cognitive decline in Alzheimer disease.
AB  - We tested the hypothesis that synaptic defects in the hippocampus of individuals
      with Alzheimer disease (AD) correlate with the severity of cognitive impairment.
      Three postmortem groups were studied: controls with normal and stable cognition;
      cognitively intact subjects with senile plaque densities diagnostic for possible
      AD (p-AD) and neurofibrillary changes characteristic of early AD (Braak stage
      III); and individuals with definite AD and neurofibrillary changes typical of
      incipient to severe AD (Braak stage III, V, or VI). Synaptophysin (a presynaptic
      vesicle protein) levels were quantified by immunoblotting of synaptic membrane
      fractions isolated from hippocampus, entorhinal cortex, caudate nucleus, and
      occipital cortex. Average synaptophysin levels were reduced in hippocampus when
      comparing definite AD to controls (55%, p < 0.0001), p-AD to control (25%, p <
      0.005), and definite AD to p-AD (30%, p < 0.05), but levels in entorhinal cortex,
      occipital cortex, and caudate nucleus were either unchanged or less significantly
      altered than in hippocampus. By univariate analysis, hippocampal synaptophysin
      levels correlated with neuropsychological measurements, including Mini-mental
      state examination scores (r = 0.83, p < 0.0001) and Blessed scores (r = 0.74, P <
      0.001), and with senile plaque densities (r = 0.89, p < 0.0001). We conclude that
      synaptic abnormalities in the hippocampus correlate with the severity of
      neuropathology and memory deficit in individuals with AD, and that this defect
      may predate neuropsychological evidence for cognitive impairment early in AD.

PMID- 9258264
TI  - Response to nutritional and growth hormone treatment in progeria.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition with an unknown
      molecular defect. Patients with HGP progressively develop failure to thrive
      (FTT), alopecia, loss of subcutaneous fat, scleroderma, stiffening of various
      joints, and severe atherosclerosis. The median life span is 13 years, and the
      main cause of death is cardiovascular complications. There are few reports of
      endocrine and metabolic studies because of the rarity of this condition, and the
      response to long-term growth hormone (GH) treatment has not been described. We
      report the results of endocrine and metabolic studies performed to investigate
      the etiology of growth failure in five patients with HGP. Additionally, the
      response to nutritional therapy (NT) and GH treatment in three of these patients
      is presented. Our results suggest that elevated GH levels are characteristic of
      this disease and that an elevated basal metabolic rate (BMR) could be the cause
      of the FTT seen in HGP. Nonaggressive NT slightly improved weight gain and growth
      velocity (GV). Combined NT and GH treatment in three patients improved the GV,
      increased the levels of growth factors, and paradoxically resulted in decreased
      BMRs. However, the response to these therapies decreased over time and did not
      seem to prevent the progression of atherosclerotic disease.

PMID- 9258265
TI  - Changes in bone mineral content in obese dieting women.
AB  - Significant reductions in total-body bone mineral density (BMD) have been
      reported in obese women who consume very-low-calorie diets. A reduction in bone
      mass is highly correlated with an increased risk of osteoporosis. The present
      study investigated whether strength training would prevent such reductions in
      dieters. Twenty-one healthy obese women weighing (mean +/- SD) 91.1 +/- 9 kg and
      aged 38 +/- 9 years were randomly assigned to receive either diet alone or diet
      plus resistance training. Both groups consumed a 925-kcal/d portion-controlled
      diet for the first 16 of 17 weeks and a 1,000 to 1,500-kcal/d balanced deficit
      diet thereafter. Bone mineral content (BMC), BMD, fat-free mass (FFM), and fat
      mass were measured with dual-energy x-ray absorptiometry (DEXA) before and after
      24 weeks of dieting. No significant changes in total-body or lumbar spine BMC and
      BMD were observed in either condition at the end of treatment. However, both
      groups demonstrated a significant loss of both BMC and BMD in the femoral neck
      and greater trochanter. Diet plus resistance training was not associated with a
      significantly better outcome on either of these measures versus diet alone. The
      results suggest that increasing the energy content of very-low-calorie diets to
      925 kcal/d may prevent the loss of total BMD, but not the loss from the femoral
      neck and greater trochanter. These findings raise a concern in light of the high
      frequency of dieting in American women.

PMID- 9258266
TI  - Serum levels of type I procollagen C-terminal propeptide, insulin-like growth
      factor-I (IGF-I), and IGF binding protein-3 in obese children and adolescents:
      relationship to gender, pubertal development, growth, insulin, and nutritional
      status.
AB  - We measured fasting serum levels of type I procollagen C-terminal propeptide
      (PICP), insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3)
      in obese children and adolescents (obese subjects [OS]) to evaluate their
      relationship to growth, gender, pubertal stage, and weight excess (WE). The
      influence of insulin, growth hormone (GH), and weight loss was also studied. The
      study population consisted of 244 OS and 236 normal-weight subjects (NWS) matched
      for age, gender, and pubertal stage. At stage I, OS had a higher standard
      deviation score (SDS) for height than NWS of both genders. During the prepubertal
      phase, growth velocity (GV) was greater in OS than in NWS of both genders, but it
      was lower in female OS at stage II and male OS at stage III. PICP increased in
      puberty, with a more rapid decrease later in female OS and NWS; prepubertal
      values were higher in OS but were reduced at pubertal stage IV to V in comparison
      to NWS. Stepwise multiple regression analysis demonstrated that GV was the only
      anthropological variable correlating with PICP. IGF-I serum values increased
      significantly in puberty and were higher in OS than in NWS at stage I for both
      genders. IGFBP-3 values of OS exceeded those of NWS at stages I to III in males
      and I to II in females. No difference was observed for males versus females in
      each group, nor was any difference observed for the IGF-I/IGFBP-3 molar ratio
      between the two groups. Using stepwise analysis, a positive correlation between
      IGF-1 and IGFBP-3 was observed in prepubertal but not in pubertal NWS. Fasting
      insulin values correlated with IGFBP-3 in OS, accounting for 24.8% of the
      variation in prepubertal subjects and 17.1% in pubertal subjects. No such
      correlation was observed in NWS. In prepubertal NWS, PICP and SDS of body mass
      index (BMI) correlated with IGF-I, accounting for 12.9% of the variation, and SDS
      of BMI correlated with IGFBP-3, explaining 27.8% of the variation. In prepubertal
      OS, no such correlations could be observed, but PICP and SDS of BMI accounted for
      14.3% of the variation in the IGF-I/IGFBP-3 molar ratio. A significant reduction
      of IGFBP-3 and an increase of the IGF-I/IGFBP-3 molar ratio were detected after
      weight loss in 40 OS. In conclusion, we demonstrated that IGF-I and IGFBP-3 are
      influenced by age, gender, sexual development, and nutritional status. Also, an
      influence of insulin on IGFBP-3 serum levels was observed in OS. The relations of
      IGF-I to PICP in NWS and of the IGF-I/IGFBP-3 molar ratio to PICP in OS support
      the concept of IGF-I influence on skeletal growth. The increased IGFBP-3 serum
      values in OS suggest a possible role in controlling the growth stimulus induced
      by nutritional status.

PMID- 9258267
TI  - Antioxidant and triglyceride-lowering effects of vitamin E associated with the
      prevention of abnormalities in the reactivity and morphology of aorta from
      streptozotocin-diabetic rats. Antioxidants in Diabetes-Induced Complications
      (ADIC) Study Group.
AB  - In this study, we evaluated the effects of vitamin E on the vascular reactivity
      and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma
      glucose, cholesterol, and triglyceride concentrations in rats were increased
      markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an
      index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic
      rats compared with controls. The rings of thoracic aorta with or without
      endothelium were mounted in organ chambers for measurement of isometric tension
      and were contracted by a single dose (10-5 mol/L) and then cumulative doses of
      noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue
      (MB) or removal of the endothelium resulted in a similar degree of enhancement in
      NA-induced contraction of control rings. STZ-diabetes increased the fast and slow
      components of NA-induced contraction in all experiments. The maximal contractile
      response of aorta to NA was also augmented by STZ-diabetes, whereas the
      sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant
      increases in the maximum contractile response and sensitivity of aorta to KCl.
      STZ-diabetic rats showed a significant reduction in the percentage of endothelial
      response (PER). A group of diabetic rats was treated from the time of diabetes
      induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation
      of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned
      plasma triglycerides toward normal levels. Diabetes-induced abnormal
      contractility and endothelial dysfunction were significantly but not completely
      prevented by vitamin E treatment. The endothelium-independent relaxation response
      to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E
      treatment. Electron microscopic examination of thoracic aorta revealed that
      normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E
      treatment can protect the morphological integrity of aorta against STZ-diabetes.
      The results suggest the following: (1) The increased triglycerides/lipid
      peroxides may be an important reason for morphological or functional disruption
      of endothelium and enhanced activation of contractile mechanisms of vascular
      smooth muscle in STZ-diabetic rats. Both contribute to an increased
      responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E
      treatment of STZ-diabetic rats can prevent the development of abnormal
      contractility and structure and endothelial dysfunction in aorta. (3) The
      triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be
      crucial for the protective effect of this vitamin on the vasculature.

PMID- 9258268
TI  - Decreased glucose effectiveness but not insulin resistance in glucose-tolerant
      offspring of Japanese non-insulin-dependent diabetic patients: a minimal-model
      analysis.
AB  - The aim of the study was to estimate insulin sensitivity (SI), insulin secretion,
      and glucose effectiveness (SG) in 10 subjects with normal glucose tolerance
      (eight men and two women) with a family history of non-insulin-dependent diabetes
      mellitus (NIDDM offspring). Ten glucose-tolerant subjects (eight men and two
      women) without a family history of NIDDM served as control subjects. All subjects
      were Japanese. They underwent a modified frequently sampled intravenous glucose
      tolerance test (FSIGT): glucose (300 mg/kg body weight) was administered, and
      insulin (20 mU/kg over 5 minutes) was infused from 20 to 25 minutes after
      glucose. SI and SG were estimated by Bergman's minimal-model method. No
      significant difference was observed in body mass index (22.6 +/- 1.5 v 21.5 +/-
      0.6 kg/m2) and fasting glucose (5.1 +/- 0.1 v 5.2 +/- 0.1 mol/L) and insulin
      (40.7 +/- 6.3 v 42.6 +/- 6.7 pmol/L). SI was not different between the two groups
      (0.83 +/- 0.11 v 0.94 +/- 0.15 x 10(-1).min-1.pmol/ L-1, P > .05). The acute
      insulin response to glucose (AIRglucose) estimated by intravenous glucose
      tolerance testing was significantly lower in the offspring than in the normal
      controls (2,139 +/- 265 v 3,438 +/- 318 pmol/L.min, P < .05). The glucose
      disappearance rate (KG) and SG were significantly diminished in the offspring
      versus normal controls (KG, 1.50 +/- 0.22 v 2.10 +/- 0.15 min-1, P < .05; SG,
      0.016 +/- 0.003 v 0.023 +/- 0.002 min-1, P < .05). Thus, glucose-tolerant
      Japanese NIDDM offspring with normal insulin sensitivity are characterized by a
      reduced AIRglucose and diminished SG. This is the first report that glucose
      resistance but not insulin resistance already exists in glucose-tolerant Japanese
      NIDDM offspring.

PMID- 9258269
TI  - Energy requirement for long-term body weight maintenance in older women.
AB  - The total dietary energy requirement of healthy, free-living older women was
      examined by determining the total energy intake (TEI) required for long-term body
      weight maintenance in nine women aged (mean +/- SD) 67 +/- 9 years (range, 56 to
      78). For 14 weeks, each woman consumed defined amounts of foods and beverages
      prepared at a General Clinical Research Center (GCRC) to provide 0.8 g protein.kg
      1.d-1 and a nonprotein energy ratio of 40% fat to 60% carbohydrate. Adjustments
      to TEI were made to keep body weight within +/-0.5 kg of each woman's starting
      body weight. All women were asked to maintain their habitual level of daily
      activity, and the energy cost of physical activity was estimated using the Yale
      Physical Activity Survey (YPAS). Resting energy expenditure (REE) was measured
      with each woman in the postabsorptive state just after awakening, using an
      indirect calorimeter at baseline and week 14. The energy requirement expressed as
      the ratio of TEI to REE was 1.82 +/- 0.15, a value 21% higher (P < .001) than the
      energy allowance of 1.5 x REE suggested for women beyond age 50 years in the 1989
      Recommended Dietary Allowances (RDAs). Using the RDAs equation to predict REE
      from body weight (pREE), the ratio of TEI to pREE was 1.73 +/- 0.18 (P < .005,
      comparison with 1.50 x REE). Estimates of the energy expenditure for physical
      activity (EEPA) based on the energy intake-balance data and the YPAS data were
      similar (3.18 +/- 0.92 and 3.14 +/- 1.42 MJ/d, respectively) for the group of
      women, but were more variable on an individual basis. Results of this long-term
      energy balance study suggest that the RDAs underestimate the dietary energy
      requirement of older women.

PMID- 9258270
TI  - Lack of deterioration of insulin action with aging in the GK rat: a contrasted
      adaptation as compared with nondiabetic rats.
AB  - One of the main characteristics of non-insulin-dependent diabetes mellitus
      (NIDDM) is an alteration of tissue insulin sensitivity, which is also observed
      during the aging process in the nondiabetic. In this study, we evaluated the
      influence of age on insulin resistance in a genetic lean model of NIDDM, the Goto
      Kakisaki (GK) rat, using the euglycemic-hyperinsulinemic clamp technique at 2,
      12, and 18 months of age. In GK rats, basal hyperglycemia (11 mmol/L) and
      insulinemia, glucose intolerance, and the specific failure of the insulin
      response to glucose apparent at 2 months of age remained stable until 18 months.
      Whatever the age, the insulin-suppressive effect on glucose production was
      significantly less in GK rats than in Wistar rats. The insulin effect on whole
      body glucose utilization was decreased at 2 months (15.8 +/- 1.0 mg/min/kg v 23.5
      +/- 2.0, P < .001) and was only mildly aggravated between 2 and 18 months (10.3
      +/- 0.9 mg/min/kg, P < .05). By contrast, in Wistar control rats, basal
      insulinemia and the insulin response to glucose markedly increased between 2 and
      18 months (2-month delta I v 18-month delta I, 1.4 +/- 0.1 mU/ml.min v 2.9 +/-
      0.3, P < .001) and glucose tolerance remained normal. In 18-month-old Wistar
      rats, the insulin-stimulated glucose utilization rate (GUR) was found to be
      markedly decreased compared with that of 2-month-old Wistar rats (9.9 +/- 0.8
      mg/min/kg v 23.5 +/- 2.0, P < .001), thus demonstrating an age-related decrease
      of insulin action. In conclusion, we find that there is no major alteration of
      insulin action due to aging in the GK rat, at variance with the pattern in
      nondiabetic rodents. It is speculated that such an adaptation in this lean model
      of NIDDM could be related to the limited capacity of these rats to expand their
      body weight with age, since it is recognized that body weight gain is largely
      responsible for the age-related impairment in peripheral insulin action in
      nondiabetic humans and nondiabetic animal models.

PMID- 9258271
TI  - Effects of ventromedial hypothalamus stimulation on glycogenolysis in rat liver
      using in vivo microdialysis.
AB  - In vivo microdialysis was applied to study the effects of ventromedial
      hypothalamus (VMH) stimulation on liver glycogenolysis under anesthesia. We
      examined glucose output and norepinephrine (NE) outflow from the liver through
      analysis of glucose and NE in the liver dialyzate. Stimulation of the VMH
      increased glucose output and NE outflow from the liver and increased the plasma
      glucose level. Similar results were obtained on hepatic nerve stimulation.
      Bilateral adrenalectomy did not abolish the glycogenolysis induced by VMH
      stimulation. NE outflow increased to a much greater extent in adrenalectomized
      rats. These data show that VMH stimulation causes glycogenolysis and glucose
      output from the liver mainly via the hepatic nerves, and that microdialysis is a
      simple and useful method for the study of liver metabolism in vivo.

PMID- 9258272
TI  - Mild adrenal and ovarian steroidogenic abnormalities in hirsute women without
      hyperandrogenemia: does idiopathic hirsutism exist?
AB  - To study ovarian and adrenal steroid profiles of women with idiopathic hirsutism,
      we compared sex steroid and basal and corticotropin (ACTH)-stimulated adrenal
      steroid levels before and after ovarian suppression induced by a long-acting
      gonadotropin-releasing hormone agonist analog (GnRH-a) in 24 hirsute women
      without hyperandrogenemia. Twelve healthy women served as controls for basal and
      ACTH-stimulated adrenal steroid levels. Serum levels of testosterone (T), sex
      hormone-binding globulin (SHBG), estradiol (E2), basal and ACTH-stimulated 17
      hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS),
      delta 4-androstenedione (delta 4-A), 11-deoxycortisol (S) and cortisol (F), and
      basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin
      levels were measured before and 21 days after 3.75 mg intramuscular triptorelin
      in hirsute women. Basal T levels and basal and ACTH-stimulated delta 4-A, DHEA,
      and DHEAS levels were not different in hirsute women with respect to controls.
      Basal and ACTH-stimulated 17OHP was elevated, and decreased to normal after
      ovarian suppression with triptorelin. Although basal and ACTH-stimulated delta 4
      A levels were normal, the delta delta 4-A/delta F and delta delta 4-A/delta 17OHP
      ratios were elevated and remained elevated after ovarian suppression, suggesting
      enhanced adrenal delta 4-17,20-lyase activity. T, F, S, and DHEAS levels were not
      affected by ovarian suppression. Basal and ACTH-stimulated 17OHP and delta 4-A,
      and stimulated DHEA concentrations were reduced with ovarian suppression, but
      their net increment and ratio to the increase of F in response to ACTH remained
      unchanged, reflecting the ovarian contribution to the secretion of these
      steroids. We conclude that idiopathic hirsute women with normoandrogenemia show
      an increase in ovarian secretion of 17OHP and a minimally increased adrenal delta
      4-17, 20-lyase activity, suggesting that mild forms of ovarian and adrenal
      functional hyperandrogenism may be present in these patients with otherwise
      unexplained hirsutism.

PMID- 9258273
TI  - Estrogen therapy enhances calcium absorption and retention and diminishes bone
      turnover in young girls with Turner's syndrome: a calcium kinetic study.
AB  - Using stable tracers of calcium, we have previously shown a significant increase
      in calcium absorption and retention in prepubertal boys treated with exogenous
      testosterone. To investigate the effects of estrogen replacement on measures of
      calcium absorption, retention, and bone turnover, we studied a group of seven
      hypogonadal girls with Turner's syndrome (mean +/- SE age, 12.5 +/- 0.7 years).
      At baseline, 42Ca intravenously (IV) and 44Ca orally were administered, and blood
      and urine samples were collected for approximately 130 hours. Estrogen therapy
      was begun as oral ethinyl estradiol (4 or 20 micrograms/d) or intramuscular depot
      estradiol given over 4 weeks, after which an identical study was repeated.
      Analysis of calcium enrichment in blood and urine was performed using mass
      spectrometry methods. After estrogen therapy, there was a significant increase in
      calcium absorption ([Va] P = .03) and total calcium retention ([Vbal] P = .04),
      similar to the effects of testosterone in boys. Bone accretion (Vo+) decreased
      after estrogen therapy (P = .004), as did resorption ([Vo-] P = .004). The
      overall rate of whole-body calcium turnover (Vt) was significantly decreased
      after estrogen administration (P = .04). These findings were opposite of those
      observed in prepubertal boys treated with testosterone. The contribution of bone
      resorption to whole-body turnover (E) also decreased after estrogen therapy (P =
      .05). These changes were associated with increased levels of 1,25
      dihydroxyvitamin D after therapy with estrogens (P = .05). We conclude that
      estrogen supplementation is significantly anabolic for calcium metabolism by
      markedly increasing calcium absorption and retention and diminishing the
      estimated whole-body calcium turnover in girls with severe hypogonadism and
      Turner's syndrome. Further studies assessing the dietary calcium and/or vitamin D
      intake and bone mineral density of hypogonadal girls whose estrogen replacement
      is intentionally delayed will further define the need for calcium or vitamin D
      supplements in the peripubertal years in this condition.

PMID- 9258274
TI  - Metabolic heterogeneity in impaired glucose tolerance.
AB  - Type II (non-insulin-dependent) diabetes mellitus is a metabolically
      heterogeneous condition, and is invariably preceded by impaired glucose tolerance
      (IGT). We examined whether metabolic heterogeneity is a feature of IGT. Three
      subject groups were studied: IGT subjects with two or more living non-insulin
      dependent diabetic relatives (IGTWF, n = 17), and IGT subjects (IGTWOF, n = 17)
      and subjects with normal glucose tolerance (NGT, n = 25) without a family history
      of diabetes. Glucose tolerance, glucose (KITTG) and nonesterified fatty acid
      (KITTNEF) insulin sensitivity, and first-phase insulin secretion (FPIS) were
      assessed by oral glucose tolerance (OGTT), insulin tolerance (ITT), and
      intravenous glucose tolerance (IVGTT) tests, respectively. Comparison of groups
      was made by ANOVA and t test. The three groups were matched for age, gender, body
      mass index (BMI), and waist to hip ratio (WHR). IGTWOF and IGTWF subjects had
      comparable 2-hour plasma glucose levels on OGTT, and insulin secretion and KITTG
      were decreased to comparable degrees. However, in comparison to IGTWF subjects,
      IGTWOF subjects had increased fasting serum triglyceride (geometric mean, 1.8
      [range, 0.8 to 4.5] v 1.1 [0.4 to 2.5] mmol. L-1, P = .02) and 2-hour plasma
      nonesterified fatty acid ([NEFA] mean +/- SD, 0.12 +/- 0.07 v 0.08 +/- 0.03
      mmol.L-1, P < .02) levels and decreased KITTNEF values (4.0 [1.7 to 8.9] v 6.2
      [2.8 to 12.1]%.min-1, P < .02). Thus, the two IGT groups had comparable changes
      in glucose metabolism, but IGTWOF subjects had additional abnormalities of lipid
      metabolism. In conclusion, metabolic heterogeneity is a feature of IGT, and this
      may reflect underlying etiological heterogeneity.

PMID- 9258275
TI  - Antioxidant inhibition of protein kinase C-signaled increases in transforming
      growth factor-beta in mesangial cells.
AB  - Protein kinase C (PKC)-signaled increases in transforming growth factor beta (TGF
      beta) have been implicated in the stimulation of matrix protein synthesis induced
      by high concentrations of glucose, thromboxane, angiotension II (AII), and other
      stimuli in cultured glomerular mesangial cells. In the present study, the effects
      of several antioxidants on mesangial cell responses to high glucose, thromboxane,
      and AII were examined. alpha-Tocopherol blocked increases in PKC, TGF beta
      bioactivity, collagen, and/or fibronectin synthesis induced in mesangial cells by
      high glucose, the thromboxane analog U46619, and AII. By contrast, alpha
      tocopherol did not alter increases in matrix protein synthesis in mesangial cells
      in response to exogenous TGF beta, a cytokine that does not activate PKC in
      mesangial cells and whose actions to stimulate matrix protein synthesis in these
      cells are not blocked by PKC inhibition or downregulation. Taurine and N
      acetylcystein similarly inhibited activation of PKC and increases in TGF beta in
      response to high glucose, U46619, and AII. alpha-Tocopherol but not taurine or N
      acetylcysteine partially blocked increases in PKC activity in mesangial cells in
      response to the diacylglycerol (DAG) analog, phorbol dibutyrate (PDBu). Thus,
      alpha-tocopherol may have direct effects on interaction of the PKC system of
      mesangial cells with DAG that are not shared by N-acetylcysteine or taurine.
      Increases in TGF beta have been implicated in the pathogenesis of
      glomerulosclerosis in diabetes and other nephropathies. The capacity of
      antioxidants to block increases in TGF beta in mesangial cells in response to
      high glucose, thromboxane, and All suggests their potential therapeutic utility
      to attenuate glomerulosclerosis.

PMID- 9258276
TI  - Fatty acid ethyl ester synthesis by the isolated perfused rat heart.
AB  - Fatty acid ethyl esters (FAEEs), nonoxidative by-products of ethanol metabolism,
      are found in various tissues and plasma after ethanol ingestion and may be
      responsible for some of the pathological changes observed in alcohol-consuming
      individuals. Previous studies demonstrated that several different enzymes,
      including lipoprotein lipase (LPL), can catalyze FAEE synthesis in vitro. We
      report that LPL catalyzes FAEE synthesis in isolated rat hearts perfused with
      chylomicrons in the presence of ethanol. Most of the FAEEs accumulated in the
      perfusate, suggesting that in vivo, plasma FAEEs derive from LPL-mediated
      synthesis. Our results are the first demonstration of the direct involvement of a
      specific enzyme, LPL, in FAEE synthesis under physiological conditions.

PMID- 9258277
TI  - Effects of heparin treatment on hemostatic abnormalities in obese non-insulin
      dependent diabetic patients.
AB  - This study was conducted to identify the mechanisms responsible for coagulative
      and fibrinolytic alterations and to study the effects of a short-term treatment
      with low-dose heparin on hemostatic abnormalities in obese non-insulin-dependent
      diabetes mellitus (NIDDM) patients. Four groups of age- and sex-matched patients
      were studied: (1) lean nondiabetic subjects (n = 30) with a body mass index (BMI)
      less than 25 kg/m2 (lean control subjects), (2) obese nondiabetic subjects (n =
      30) with a BMI greater than 30 kg/m2 (obese control subjects), (3) lean NIDDM
      patients (n = 30), and (4) obese NIDDM patients (n = 30). All subjects were
      tested on the following parameters: fibrinogen, factor VII, prothrombin fragment
      1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), tissue plasminogen
      activator (t-PA) antigen (Ag) before and after venous occlusion (VO), and
      plasminogen activator inhibitor type-1 (PAI-1) activity pre- and post-VO. In
      addition, all these parameters were evaluated in obese NIDDM patients after 10
      days of treatment with a single dose of 12,500-U/d subcutaneous calcium heparin
      and after a 10-day washout period. At baseline, obese nondiabetic subjects, lean
      NIDDM patients, and especially obese NIDDM patients displayed significantly (P <
      .01) higher levels of fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and
      PAI-1 pre- and post-VO and significantly (P < .01) lower levels of t-PA(Ag) post
      VO. In obese NIDDM patients treated with heparin fibrinogen, factor VII, F1 + 2,
      TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO levels significantly (P < .01)
      decreased and t-PA(Ag) post-VO levels significantly (P < .01) increased at the
      end of treatment. Our findings demonstrate in obese nondiabetic subjects, lean
      NIDDM patients, and especially obese NIDDM patients the hemostatic abnormalities
      contributing to an enhanced risk of thrombotic complications. We conclude that in
      obese NIDDM patients, short-term treatment with heparin may reduce this
      thrombophilic state and have a potential benefit in the progression of diabetic
      microvascular and macrovascular disease and needs further investigation.

PMID- 9258278
TI  - The insulin sensitizer, BRL 49653, reduces systemic fatty acid supply and
      utilization and tissue lipid availability in the rat.
AB  - Thiazolidinediones are oral insulin-sensitizing agents that may be useful for the
      treatment of non-insulin-dependent diabetes mellitus (NIDDM). BRL 49653
      ameliorates insulin resistance and improves glucoregulation in high-fat-fed (HF)
      rats. It is known that thiazolidinediones bind to the peroxisome proliferator
      activated receptor (PPAR gamma) in fat cells, but the extent to which the
      improved glucoregulation and hypolipidemic effects relate to adipose tissue
      requires clarification. We therefore examined BRL 49653 effects on lipid
      metabolism in HF and control (high-starch-fed [HS]) rats. The diet period was 3
      weeks, with BRL 49653 (10 mumol/kg/d) or vehicle gavage administered over the
      last 4 days. Studies were performed on animals in the conscious fasted state. In
      HF rats, rate constants governing 3H-palmitate clearance were unaffected by BRL
      49653. This finding, taken with a concurrent decrease of fasting plasma
      nonesterified fatty acids (NEFA) (P < .01, ANOVA), demonstrated that systemic
      NEFA supply and hence absolute utilization are reduced by BRL 49653. Hepatic
      triglyceride (TG) production (HTGP) assessed using Triton WR1339 was unaffected
      by diet or BRL 49653. In liver, BRL 49653 increased insulin-stimulated conversion
      of glucose into fatty acid in both HF (by 270%) and HS (by 30%) groups (P < .05).
      Relative to HS rats, HF animals had substantially elevated levels of muscle
      diglyceride (diacylglycerol[DG] by 240%, P < .001). BRL 49653 significantly
      reduced muscle DG in HF (by 30%, P < .05) but not in HS rats. The agent did not
      reduce the intake of dietary lipid. In conclusion, these results are consistent
      with a primary action of BRL 49653 in adipose tissue to conserve lipid by
      reducing systemic lipid supply and subsequent utilization. The parallel effects
      of diet and BRL 49653 treatment on insulin resistance and muscle acylglyceride
      levels support the involvement of local lipid oversupply in the generation of
      muscle insulin resistance.

PMID- 9258279
TI  - Measurement of very low stable isotope enrichments by gas chromatography/mass
      spectrometry: application to measurement of muscle protein synthesis.
AB  - Measurement of muscle protein synthesis using stable isotopically labeled tracers
      usually requires isotope ratio mass spectrometry (IRMS) because of the need to
      measure very low enrichments of stable isotopically labeled tracers (tracer to
      tracee ratio [TTR], 0.005% to 0.10%). This approach is laborious, requiring
      purification of the metabolite of interest and combustion to a gas for IRMS
      analysis, and is best suited for use with 13C tracers. We have developed an
      approach whereby low enrichments can be conveniently measured by a conventional
      gas chromatography/mass spectrometry (GC/MS) instrument. The approach includes
      three critical elements: (1) use of a highly substituted tracer containing three
      or more labeled atoms, to measure enrichment above a very low natural abundance
      of highly substituted isotopomers; (2) use of a highly substituted natural
      abundance isotopomer as a base ion for comparison rather than the most abundant m
      + 0 isotopomer, to reduce the dynamic range of the isotopomer ratio measurement;
      and (3) a sensitive mass spectrometric analysis that measures the natural
      abundance of the isotopomer used as a tracer with a high signal to noise ratio (>
      100:1). This approach was used to measure the rate of synthesis of muscle protein
      following a primed continuous infusion of L-[13C6]-phenylalanine (PHE) in eight
      fasted dogs and L-[2H3]-leucine in five fasted human subjects. Values for [13C6]
      PHE enrichment by GC/MS rates were virtually identical to those obtained by a
      conventional approach using high-performance liquid chromatography (HPLC) to
      isolate PHE, combustion to CO2, and measurement of 13CO2 enrichment by IRMS (IRMS
      enrichment = 0.9988 x GC/MS enrichment, R2 = .891), resulting in identical values
      for muscle fractional synthesis rates ([FSRs] mean +/- SEM: 2.7 +/- 0.2 and 2.5
      +/- 0.2%/d for GC/MS and IRMS, respectively). Human muscle synthesis rates
      measured by GC/MS analysis of [2H3]-leucine enrichment (1.90 +/- 0.17%/d) were
      similar to published values based on IRMS analysis using a 1- 13C-leucine tracer.
      We conclude that compared with the IRMS approach, the GC/MS approach offers
      faster throughput, has a lower sample requirement, and is suitable for a wider
      variety of tracers such as 2H. The principles outlined here should be applicable
      to the measurement of low enrichments by GC/MS in a wide variety of stable
      isotope tracer applications.

PMID- 9258280
TI  - Increased intracellular calcium and altered phorbol dibutyrate binding to intact
      platelets in young subjects with insulin-dependent and non-insulin-dependent
      diabetes mellitus.
AB  - Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact
      platelets of young patients with insulin-dependent (IDDM) and non-insulin
      dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances
      in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i
      in platelets of the IDDM group (135 +/- 20 nmol/L) under basal conditions was
      significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019),
      whereas at 60 seconds after stimulation with 0.1 National Institutes of Health
      (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was
      significantly higher than that of the controls (347 +/- 22 nmol/L, P = .003) and
      IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate
      (PdBu) maximal binding capacity (Bmax) in the IDDM group was significantly lower
      than that in the control group either under basal conditions or after stimulation
      with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was
      significantly lower than that in the controls only after stimulation with
      thrombin (P = .047). The Kd for PdBu of the IDDM group was lower than that of the
      control group under basal conditions (P = .017). When analyzing the pooled data
      of all subjects, a significant correlation was observed between Bmax and Kd
      (under basal conditions, r = .544, P < .0001; after stimulation, r = .601, P <
      .0001). Our results support the idea that the increased affinity for PdBu may
      compensate for the decreased binding capacity. We interpret the data as
      indicating that the change in the binding of phorbol ester to protein kinase C
      (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis
      of diabetes mellitus. Our study indicates that such metabolic derangements of
      [Ca2+]i have already been developing in young diabetic patients.

PMID- 9258281
TI  - Low-density lipoprotein particle size is not a discriminating marker for
      atherogenic risk in male offspring of parents with early coronary artery disease.
AB  - The aim of this study was to assess the importance of low-density lipoprotein
      (LDL) particle size as a marker of atherogenic risk in male offspring of a parent
      with early coronary artery disease (CAD) before the age of 60 years. CAD-positive
      (CAD+) offspring were recruited into two groups based on age, 15 to 30 years (n =
      20) and 31 to 45 years (n = 41), and matched to CAD-negative (CAD-) offspring by
      age and body mass index (BMI) (n = 20 and 21 per group). LDL peak particle
      diameter was assessed by polyacrylamide gradient gel electrophoresis. There was
      no significant difference in LDL peak particle diameter between CAD+ and CAD-
      offspring (26.2 +/- 0.1 v 26.2 +/- 0.1 nm, mean +/- SE). There was also no
      difference between CAD+ offspring and CAD- offspring when comparisons were made
      within their own age group (26.5 +/- 0.1 nm in younger CAD+ offspring v 26.2 +/-
      0.1 nm in younger CAD- offspring, and 26.0 +/- 0.1 nm in older CAD+ offspring v
      26.1 +/- 0.2 nm in older CAD- offspring). Peak particle diameter was
      significantly greater in younger CAD+ offspring than in older CAD+ offspring
      (26.5 +/- 0.1 v 26.0 +/- 0.1 nm, P < .05). We conclude that small LDL particle
      size is not a discriminating marker for early atherogenic risk, and that
      measurement of LDL particle size has limited value in the assessment of coronary
      risk, at least in the age ranges we studied.

PMID- 9258283
TI  - Maternal and fetal modulators of lipid metabolism correlate with the development
      of preeclampsia.
AB  - The pregnancy syndrome preeclampsia is associated with placental dysfunction,
      dyslipidemia, and endothelial cell activation, and is a major cause of maternal
      and fetal morbidity and mortality. In this report, a nested case-control study of
      matched preeclamptic and normal pregnant women was used to investigate the
      association of maternal and fetal modulators of lipid metabolism with pregnancy
      outcome. Maternal body mass index (BMI), triglyceride levels, and nonesterified
      fatty acid (NEFA) concentrations were all significantly increased in women who
      developed preeclampsia (P < .01). Human placental lactogen (hPL), which is
      secreted by the syncytiotrophoblast layer of the fetal placenta and reportedly
      has lipolytic activity, also was found to be elevated in women with preeclampsia
      (P < .01). By contrast, hemoglobin levels were not found to be statistically
      different between the two groups of women, indicating that the increased plasma
      lipids and hPL were not a result of hemoconcentration in preeclamptic patients.
      The results suggest a multihit hypothesis for the pathophysiology of preeclampsia
      in which maternal obesity and a placental lipolytic hormone (hPL) converge to
      adversely affect free fatty acid concentrations in the maternal circulation.

PMID- 9258282
TI  - Plasma total homocysteine concentrations in epileptic patients taking
      anticonvulsants.
AB  - Plasma total homocysteine (tHcy) and serum folate (FA) concentrations were
      measured in 130 epileptic patients taking anticonvulsant drugs. A significant
      inverse correlation was found between FA and tHcy. This was greater in the older
      group (> or = 15 years) than in the younger group (1 to 14 years). There were
      four FA-deficient patients (FA concentration < 3 ng/mL regardless of symptoms),
      including three patients in the older group and one in the younger group. All FA
      deficient patients had received long-term treatment (> 7 years) with multiple
      anticonvulsants. Their tHcy levels were higher than the 90th percentile of those
      in control subjects. Two patients showed extremely high levels of tHcy (57.9 and
      29.1 mumol/L) and subnormal plasma methionine levels. After FA therapy, their
      tHcy decreased to levels the same as or less than those of control subjects and
      FA increased to above the normal range. Based on these findings, we conclude that
      measuring FA and tHcy concentrations may be useful for preventing thrombosis due
      to hyperhomocysteinemia in epileptic patients taking anticonvulsants,
      particularly those who receive long-term treatment with multiple agents.

PMID- 9258284
TI  - Assessment of fat-mass loss during weight reduction in obese women.
AB  - Methods for assessing body fat mass (FM) loss were compared in 32 obese (body
      mass index [BMI], 29 to 41 kg/m2) premenopausal women before and after a weight
      loss of 13.0 +/- 3.4 kg (mean +/- SD). A four-component (4C) model was used as
      the criterion. The other methods were as follows: three-component models (body
      density with total body water [3W] or bone minerals [3M]), underwater weighing,
      dual-energy x-ray absorptiometry ([DXA] XR-26, software 2.5.2; Norland, Ft
      Atkinson, WI), bioelectric impedance analysis (BIA) with an obese-specific
      equation [Segal et al), skinfolds (Durnin and Womersley), and an equation with
      BMI (Deurenberg et al). The 3W model (bias +/- SD, 0.5 +/- 0.4 kg), XR-26 (0.6 +/
      2.1 kg), and BMI equation (-0.3 +/- 2.1 kg) gave practically unbiased mean
      estimations of fat loss. All other methods underestimated fat loss by at least
      1.6 kg (range of bias, -2.7 to -1.6 kg). The small bias (0.7 +/- 1.0 kg) between
      underwater weighing and model 4C before weight reduction indicates that the two
      component assumptions were valid in premenopausal, weight-stable obese women.
      However, particularly the water fraction of the fat-free body component (4C
      model) was increased after weight reduction (before, 72.9% +/- 1.4%; after, 75.7%
      +/- 2.2%), making both underwater weighing and the 3M model uncertain for
      assessment of body composition changes. A general tendency for overestimating FM
      was seen before and more clearly after weight reduction. However, most methods
      underestimated fat loss, apparently because of unexpected changes in hydration of
      the fat-free body component.

PMID- 9258286
TI  - Ethical review is needed for public health studies.

PMID- 9258285
TI  - Angiotensin I-converting enzyme and angiotensinogen gene polymorphisms in non
      insulin-dependent diabetes mellitus. Lack of relationship with diabetic
      nephropathy and retinopathy in a Caucasian Mediterranean population.
AB  - Genotypic abnormalities of the renin-angiotensin system have been suggested as a
      risk factor for the development of microangiopathic complications in diabetic
      patients. We studied the relationship of either an insertion-deletion
      polymorphism in the angiotensin-converting enzyme (ACE) gene and the M235T and
      T174M variant polymorphisms of the angiotensinogen (AGT) gene in non-insulin
      dependent diabetes mellitus (NIDDM) patients and its relationship with
      cardiovascular complications. A total of 193 NIDDM patients (89 men and 104 women
      aged 59.2 +/- 10.0 years; diabetes duration, 13.2 +/- 6.2 years) and 90 control
      subjects (42 men and 48 women aged 45.4 +/- 12.6 years) were recruited for the
      association study. Distribution of the genotype or allelic frequencies for all
      the studied polymorphisms did not differ significantly between controls and NIDDM
      patients. ACE and AGT genes did not display any difference in clinical or
      metabolic parameters according to each gene's genotype for either the control or
      the NIDDM group. For evaluation of nephropathy and retinopathy, NIDDM patients
      were matched with subjects not having microangiopathic complications. Thus, a
      total of 60 patients had diabetic nephropathy and were compared with 100 patients
      with normoalbuminuria. Sixty-eight NIDDM patients had diabetic retinopathy, and
      92 patients presented no signs of retinopathy. There were no differences in
      genotypic or allelic distribution between NIDDM patients for either the presence
      or absence of retinopathy or nephropathy. We conclude that the ACE and AGT
      polymorphisms do not contribute to the genetic susceptibility to diabetic
      nephropathy and retinopathy in a caucasian Mediterranean population.

PMID- 9258288
TI  - A resource guide on violence and teen pregnancy.

PMID- 9258289
TI  - DHHS launches toll-free service for prenatal care.

PMID- 9258290
TI  - Drive-by deliveries. Influences on state legislators.

PMID- 9258291
TI  - A missed opportunity.

PMID- 9258293
TI  - Drive-by deliveries. A senator's perspective.

PMID- 9258294
TI  - Cigarette taxes. The straw to break the camel's back.
AB  - Teenage cigarette smoking is sensitive to the price of cigarettes. The most
      recent research suggests that a 10% increase in price would reduce the number of
      teenagers who smoke by 7%. If the proposed 43-cent hike in the Federal excise tax
      rate on cigarettes contained in the Hatch-Kennedy Bill were enacted, the number
      of teenage smokers would fall by approximately 16%. This translates into more
      than 2.6 million fewer smokers and more than 850,000 fewer smoking-related
      premature deaths in the current cohort of 0 to 17-year-olds. Adjusted for
      inflation, the current 24-cent-a-pack tax costs the buyer about half of the
      original cigarette tax of 8 cents imposed in 1951. A substantial tax hike would
      curb youth smoking; this strategy should move to the forefront of the antismoking
      campaign.

PMID- 9258296
TI  - Radioactivity in municipal sewage and sludge.
AB  - OBJECTIVE: To determine the environmental consequences of discharges of
      radioactivity from a large medical research facility into municipal sewage,
      specifically 131I activity in sewage sludge, and the radiation exposures to
      workers and the public when sludges are incinerated. METHODS: The authors
      measured radioactivity levels in the sludge at the Ann Arbor, Michigan, Waste
      Water Treatment Plant following radioiodine treatments of two patients at the
      University of Michigan hospital complex and performed a series of calculations to
      estimate potential radiation doses due to releases of 131I from incineration of
      sewage sludge. RESULTS: Approximately 1.1% of the radioactive 131I administered
      therapeutically to patients was measured in the primary sludge. Radiation doses
      from incineration of sludge were calculated to be 0.048 millirem (mrem) for a
      worker during a period in which the incinerator filtration system failed, a
      condition that could be considered to represent maximum exposure conditions, for
      two nine-hour days. Calculated results for a more typically exposed worker (with
      the filtration system in operation and a 22-week period of incineration) yielded
      a committed effective dose equivalent of 0.066 mrem. If a worker were exposed to
      both conditions during the period of incineration, the dose was calculated to be
      0.11 mrem. For a member of the public, the committed effective dose equivalent
      was calculated as 0.003 mrem for a 22-week incineration period. Exposures to both
      workers and the public were a very small fraction of a typical annual dose (about
      100 mrem excluding radon, or 300 mrem with radon) due to natural background
      radiation. Transport time to the treatment plant for radioiodine was found to be
      much longer than that of a normal sewage, possibly due to absorption of iodine by
      organic material in the sewer lines. The residence time of radioiodine in the
      sewer also appears to be longer than expected. CONCLUSION: 131I in land-applied
      sludge presents few health concerns because sufficient decay occurs before it can
      reach the public however, incineration, which is done in winter months, directly
      releases the 131I from sewage sludge to the atmosphere, and even though exposures
      to both workers and the public were found to be considerably lower than 1% of
      natural background, incineration of sludge in a pathway for public exposure.
      Although 131I was readily measurable in sewage sludge, only about 1% of the
      radioione administered to patients was found in the sludge. The fate of the
      remaining radioactivity has not been established; some may be in secondary and
      tertiary residuals, but it is quite likely that most passed through the plant and
      was discharged in dilute concentrations in plant emissions. The behavior of
      radioiodine and other radioactive materials released into municipal seweage
      systems, such as those from large medical facilities, is not yet well understood.

PMID- 9258295
TI  - Private health care in Canada: savior or siren?
AB  - In canada, health care is publicly insured and available to all at no charge.
      Recently, financial pressures have threatened the system and led to considerable
      debate about how to save it. One proposal is to permit privately funded health
      care alongside the public system, resulting in what is popularly called a two
      tiered system. This paper presents some of the arguments for and against two
      tiered health care. Using as an example cataract surgery-a procedure that is
      available both publicly and privately-the authors look at some common beliefs
      about private health care in Canada. They conclude that the growth in private
      sector cataract surgery does not appear to be related to cutbacks or rationing,
      that private access does not necessarily shorten waiting times, and that,
      contrary to popular belief, it is not only the well-to-do who pay for private
      surgery in Canada.

PMID- 9258297
TI  - Dental caries prevalence and treatment levels in Arizona preschool children.
AB  - OBJECTIVES: To assess the prevalence of dental caries in a large group of
      preschool children, to determine the extent to which the children received dental
      treatment, to examine the association between demographic and socioeconomic
      factors and the prevalence of caries, and to compare these findings with those
      from previous studies of preschool populations in the United States. METHODS:
      Dental caries exams were performed on 5171 children ages 5 months through 4
      years, and a parent or other caregiver was asked to complete a questionnaire
      giving information about the child and her or his household. The children were
      recruited from Head Start programs; Women, Infants, and Children (WIC) nutrition
      programs; health fairs; and day care centers in a representative sample of
      Arizona communities with populations of more than 1000 people. RESULTS: Of the
      994 one-year-old children examined, 6.4% had caries, with a mean dmft (decayed,
      missing [extracted due to caries], and filled teeth) score of 0.18. Nearly 20% of
      the 2-year-olds had caries, with a mean dmft of 0.70. Thirty-five percent of the
      3-year-olds had caries, with a mean dmft of 1.35, and 49% of the 4-year-olds had
      caries, with a mean dmft of 2.36. Children whose caregivers fell into the lowest
      education category had a mean dmft score three times higher than those with
      caregivers in the highest education category. Children with caregivers in the
      lowest income category had a mean dmft score four times higher than those with
      caregivers in the highest category. Children younger than age 3 had little
      evidence of dental treatment, and most of the children with caries in each age
      group had no filled or extracted teeth. CONCLUSIONS: The data show that dental
      caries is highly prevalent in this preschool population, with little of the
      disease being treated. Timing of diagnostic examinations and prevention
      strategies for preschool children need to be reconsidered, especially for
      children identified as having a high risk of caries.

PMID- 9258298
TI  - The relationship between prenatal health behavior advice and low birth weight.
AB  - OBJECTIVES: The purposes of the study were (a) to examine the relationship
      between the health behavior advice recommended by the Public Health Service
      Expert Panel on the Content of Prenatal Care and the risk of low birth weight and
      (b) to describe the type and frequency of health behavior advice offered to a
      group of pregnant women. METHODS: The authors used data from the National
      Institute of Child Health and Human Development/Missouri Maternal and Infant
      Health Survey, a follow-back survey of women who had delivered very low birth
      weight infants and of matched control subjects who had delivered moderately low
      birth weight and normal birth weight infants. Frequency distributions for
      different types of prenatal health behavior advice were examined for the 2205
      participants, and logistic regression analyses were used to determine whether
      there was a relationship between birth weight and receiving the advice
      recommended by the Expert Panel. RESULTS: Only 10.4% of mothers reported
      receiving all seven types of health behavior advice recommended by the Expert
      Panel. Women who did not receive all seven types of advice were 1.5 times more
      likely to deliver a very low birth weight infant than a normal birth weight
      infant. CONCLUSIONS: Further research is needed to better understand the
      relationship between health education and birth weight.

PMID- 9258299
TI  - The effect of incarceration during pregnancy on birth outcomes.
AB  - OBJECTIVE: This study examined the effect of incarceration during pregnancy on
      infant birth weight. METHODS: North Carolina prison records were matched to North
      Carolina birth certificates and health services records to identify 94 women who
      were incarcerated during one pregnancy but not incarcerated during another
      pregnancy. Paired analyses examined differences between the pregnancies in terms
      of the women's characteristics and use of health services. A generalized
      estimating equations analysis modeled infant birth weight as a function of the
      number of days that a woman was incarcerated during pregnancy, accounting for the
      correlation between the birth weights of two infants born to the same mother and
      several potentially confounding variables. RESULTS: Since the women were
      significantly more likely to have been incarcerated during the second of the pair
      of pregnancies, as a group they were significantly older and had more children at
      the time of the incarcerated pregnancy than at the time of the home pregnancy.
      After controlling for important covariates, a higher number of pregnancy days
      spent incarcerated was found to be associated with higher infant birth weight.
      CONCLUSION: These findings suggest that aspects of the prison environment such as
      shelter and regular meals may enhance pregnancy outcomes among very high risk
      women. Health professionals should join others in efforts to assure that health
      promoting resources such as adequate shelter, nutritional support, and substance
      abuse treatment programs are available to all pregnant women.

PMID- 9258300
TI  - PHS in the Queen City: a watershed development.
AB  - For over a century, Cincinnati, Ohio, has been at the center of the nation's
      efforts to control water pollution. Site and subject of PHS activities to
      understand, manage, and prevent pollution, Cincinnati now carries on this public
      health legacy as home to EPA's water pollution programs. From ante-bellum way
      station for primary care and the seat of early 20th century scientific
      contributions to vibrant center for the development of environmental health
      programs after World War II, the Queen City has truly provided a number of
      watershed developments in the history of public health.

PMID- 9258301
TI  - Nondepolarizing neuromuscular blocking drugs in the intensive care unit: a
      clinical review.
AB  - BACKGROUND: The use of nondepolarizing neuromuscular blocking drugs (NDNMBDs) via
      continuous infusion in the intensive care unit (ICU) is gaining in popularity.
      Several new NDNMBDs have been developed recently; these drugs vary in their
      elimination, metabolism, and half-lives. METHODS: A review of the recent English
      language literature was done, with those articles relevant to the ICU being
      incorporated into this paper. RESULTS: The six most frequently used NDNMBDs,
      consisting of atracurium, cisatracurium, doxacurlum, pancuronium, rocuronium, and
      vecuronium, were reviewed. The neuromuscular junction and impulse transmission,
      clinical monitoring, clinical pharmacology, the elimination and metabolism, the
      adverse reactions, and the drug interactions of these NDNMBDs are reviewed.
      CONCLUSIONS: The use of NDNMBDs is progressively increasing in ICUs. Proper
      understanding of normal neuromuscular physiology, clinical pharmacology, and drug
      interactions is essential to optimize patient care and to minimize the risk of
      adverse reactions.

PMID- 9258302
TI  - Bipolar illness.
AB  - BACKGROUND: Within the past 5 years, several factors have altered our view of the
      diagnosis, prognosis, treatment, and genetics of bipolar illness. METHODS:
      Significant advances in these areas are reviewed. RESULTS: Diagnostic changes
      include establishment of symptom duration requirements that limit confusion with
      affective instability. Prognostic insights include the realization that illness
      likely begets illness and, conversely, that adequate control is probably
      instrumental in improving long-term prognosis. Therapeutic advances are marked by
      the Food and Drug Administration approval of divalproex for acute mania.
      CONCLUSIONS: Genetic and family studies suggest that (1) bipolar illness is a
      discrete condition, not related to unipolar depression; and (2) bipolar illness
      may manifest a phenomenon known as anticipation (worsening of the disease with
      succession generations), which may be related to a specific nucleic acid
      abnormality.

PMID- 9258303
TI  - Correlation of menstrual cycle at time of breast cancer surgery to disease-free
      and overall survival.
AB  - The timing of surgery during the menstrual cycle of premenopausal breast cancer
      patients was correlated with their disease-free survival (DFS) and overall
      survival (OS). The study included 150 premenopausal patients treated for breast
      cancer between 1977 and 1992. The data were analyzed using three different
      menstrual cycle phase categorization schemes: (1) days 0 to 6 and 21 to 32 vs 7
      to 20; (2) days 0 to 2 and 13 to 32 vs 3 to 12; and (3) days 0 to 14 vs 14 to 32.
      Two different surgery dates used for analysis were biopsy date and definitive
      surgery date. There was no association of the timing of surgery with OS. Only one
      categorization scheme correlated with DFS (scheme No. 2), and this correlation
      was significant using either surgery or biopsy dates. Thus, premenopausal breast
      cancer patients who have biopsy and/or definitive surgery during their
      perimenstrual phase (days 0 to 2 or after day 13) of the menstrual cycle may have
      a longer DFS than patients operated on during their midcycle phase (days 3 to
      13); however, this may not affect overall survival.

PMID- 9258304
TI  - Back pain in children and adolescents: a retrospective review of 648 patients.
AB  - Back pain in children has long been considered a serious condition with an
      organic cause. The staff of the Shriner's Hospital had been informally noting
      that diagnoses among children with back pain had been changing. We conducted a
      retrospective study of 648 patients with spinal disorders treated at the
      Shriner's Hospital for Crippled Children, Spokane Unit, between January 1991 and
      June 1993. The patients were divided into two groups: those with pain and those
      without pain. It was found that back pain with no organic cause was the primary
      diagnosis in 57% of the group having pain. Only one child had a diagnosis of
      malignancy, and there were no cases of active infection. In the group with pain,
      three interesting associations were found concerning psychosocial problems,
      disability, and litigation. It was found that the diagnoses in children with back
      pain treated at this referral center during the study period parallel those in
      the adult population with back pain.

PMID- 9258305
TI  - Solitary fibrous tumors: a series of lesions, some in unusual sites.
AB  - Solitary fibrous tumor (SFT) is a rare neoplasm that, in addition to its classic
      presentation as a pleural-based mass, can also be encountered in unusual sites.
      The main difficulty in making the diagnosis of SFTs results from the
      unfamiliarity with its diverse clinical and pathologic features. This series of
      SFTs, some with unusual clinicopathologic presentation, included nine women and
      two men, ranging in age from 28 years to 74 years (five in pleura, one in lung
      parenchyma, one in breast, and four in mediastinum). The tumors were locally
      excised in eight cases and were resected along with portions of lung parenchyma
      in three. A panel of immunohistochemical stains was used to characterize these
      tumors. They were all vimentin-positive and, with the exception of one case, CD34
      positive. Tumors were negative with antibodies directed against cytokeratin,
      factor VIII-related antigen, S-100 protein, muscle-specific actin, and smooth
      muscle actin. Various diagnoses were initially rendered for these clinically and
      pathologically diverse lesions by the examining pathologists. Awareness of the
      various gross and microscopic patterns of these tumors, the possibility of
      occurring in unusual sites, and the use of immunohistochemical stains,
      particularly CD34, should eliminate most of the difficulties in arriving at a
      correct diagnosis. One patient died of metastatic breast cancer; all other
      patients were alive and well with a median follow-up of 17 months.

PMID- 9258306
TI  - Increased incidence of non-transitional cell carcinoma of the bladder in women of
      the Texas Gulf Coast region.
AB  - The objective of our study was to verify a suspected increased incidence of non
      transitional cell carcinoma (TCC) of the bladder in female patients treated at
      our institution. The study included 169 patients, 83% of whom resided in the
      Texas Gulf Coast region. Tumors were considered TCC or non-TCC on the basis of
      their predominant histologic pattern. The incidence of non-TCC among men (8.1%)
      was comparable with data from American tumor registries and European studies. In
      contrast, our female patients exhibited a marked increased incidence of non-TCC
      (42.3%), which is approximately five times higher than that in other series. All
      male and female patients with non-TCC had invasive disease. History of urinary
      tract infections was strongly associated with non-TCC. Our results suggest that
      our sample of the female population in the Texas Gulf Coast region has a
      significantly high incidence of non-TCC. This unusual trend merits further
      investigation.

PMID- 9258307
TI  - Prevalence of obesity with increased blood pressure in elementary school-aged
      children.
AB  - The objectives of this study were to estimate the prevalence of obesity in school
      aged children in Jefferson County, Alabama; to learn when school-aged children
      become obese; to determine the susceptible groups; and to study the association
      between obesity and blood pressure. During the school year, 5,953 children,
      ranging in age from 5 years to 11 years, were screened for weight, height, and
      blood pressure, using standardized techniques. We found that obesity, defined as
      > or = 120% of ideal body weight for height, is prevalent in 5-year-old to 11
      year-old children. The prevalence of obesity in girls at age 5 was 23% in blacks
      and 10% in whites, rising to 47% in blacks and 27% in whites by age 11. In boys,
      the prevalence of obesity at age 5 was 13% in blacks and 6% in whites, rising to
      29% in blacks and 22% in whites by age 11. The prevalence of obesity is
      significantly greater in black than in white children and is also significantly
      greater in girls than boys. The systolic and diastolic blood pressures were
      significantly higher in obese than in non-obese children. We conclude that the
      significant prevalence of childhood obesity and an associated complication,
      increased blood pressure, emerge in school-aged children. Thus, we recommend
      investigations of prevention and intervention programs to be used in the school
      setting.

PMID- 9258308
TI  - Prevalence of coronary heart disease risk factors among rural blacks: a community
      based study.
AB  - BACKGROUND: Coronary heart disease (CHD) remains the most common cause of death
      among blacks, and the difference in CHD mortality between blacks and whites is
      growing. This trend may be due in part to higher rates of CHD risk factors among
      blacks. This study was done to determine the prevalence of CHD risk factors among
      a population-based sample of 403 rural blacks in Virginia. METHODS: Community
      based screening evaluations included the determination of exercise and smoking
      habits, blood pressure, height, weight, total and high-density lipoprotein (HDL)
      cholesterol, and glycosylated hemoglobin. RESULTS: The prevalences of smoking
      (32.5% of men, 20.0% of women), high cholesterol (16.6% of men, 18.9% of women)
      and sedentary lifestyle (37.5% of men, 66.7% of women) were similar to
      prevalences reported for other black populations. However, the prevalences of
      diabetes (13.6% of men, 15.6% of women), hypertension (30.9% of men, 43.1% of
      women), and obesity (38.7% of men, 64.7% of women) were higher than those
      reported elsewhere. Increased body mass index was significantly associated with
      higher prevalences of hypertension, diabetes, and low HDL cholesterol.
      CONCLUSIONS: Innovative methods are needed to decrease the high risk factor
      prevalences among this population.

PMID- 9258309
TI  - Conscious sedation with high-dose midazolam for pediatric gastrointestinal
      endoscopy.
AB  - BACKGROUND: Midazolam is used frequently to sedate children for gastrointestinal
      endoscopy. The sedative dosage of intravenous midazolam commonly reported in
      children is up to 0.3 mg/kg. We hypothesized that larger doses of midazolam could
      be used for pediatric endoscopy. METHODS: We retrospectively reviewed the medical
      records of 116 pediatric patients (aged 1 year to 18 years) who had endoscopy.
      The efficacy and side effects of sedation in 45 patients who received midazolam
      doses of > or = 0.3 mg/kg were compared with the same effects in 71 children who
      received < 0.3 mg/kg. RESULTS: All patients received approximately 1 mg/kg
      meperidine (up to 50 mg) intravenously. The blood pressure, pulse rate,
      respiratory rate, oxygen saturation, degree and duration of sedation, and
      incidence of side effects such as hypotension, hypoxia, or vomiting were similar
      in both groups. CONCLUSIONS: Intravenous doses of midazolam > 0.3 mg/kg can be
      used for conscious sedation in children.

PMID- 9258310
TI  - Seizure after overdose of tramadol.
AB  - Tramadol (Ultram) is a new analgesic agent with a dual mechanism of action that
      includes weak agonistic effects at the mu-opioid receptor as well as inhibition
      of neurotransmitter (serotonin, norepinephrine) re-uptake. Although it has proven
      to be a safe and effective agent for the control of pain, adverse effects can
      occur with its use. I report the occurrence of seizure activity after the
      inadvertent administration of 4 mg/kg of tramadol to a child. Previous reports of
      seizure activity after tramadol administration are reviewed and the treatment of
      this problem is discussed.

PMID- 9258312
TI  - Cutaneous protothecosis in association with the acquired immunodeficiency
      syndrome.
AB  - We report a case of protothecosis that occurred in the skin over the left tibial
      region of a 25-year-old man with the acquired immunodeficiency syndrome (AIDS).
      The lesion was noticed a few months after he swam in a lake in south Alabama.
      Biopsy and culture revealed Prototheca wickerhamii. We believe this is only the
      second reported case of cutaneous protothecosis in association with AIDS.

PMID- 9258311
TI  - High grade dysplasia/esophageal adenocarcinoma in short segment Barrett's
      esophagus.
AB  - Short segment Barrett's esophagus (SSBE) is a frequent finding in patients having
      endoscopy, but its clinical significance is not fully understood. With the rising
      incidence of esophageal adenocarcinoma, a potential role of SSBE has been
      suggested. Biopsy of such lesions may have to be done when seen on endoscopy.

PMID- 9258313
TI  - Brodifacoum rodenticide ingestion in a patient with shigellosis.
AB  - Factitious disorders are characterized by the intentional feigning or induction
      of signs and/or symptoms in order to assume the sick role. The spectrum of
      diseases and symptoms simulated is extensive. Although some patients may seek
      only the gratifications of the sick role, typically patients seek health care for
      their afflictions. We report the case of a woman with a history of numerous
      unexplainable illnesses and laboratory findings who had shigellosis. On routine
      evaluation, a severe prothrombin coagulopathy was discovered and later determined
      to be caused by brodifacoum, a "superwarfarin" drug found in potent rodenticides.
      The patient was successfully treated with daily vitamin K. She continued to deny
      intentional or accidental ingestion but did consent to psychiatric treatment.

PMID- 9258315
TI  - Hodgkin's disease associated with neurologic paraneoplastic syndrome.
AB  - In this case of neurologic paraneoplastic syndrome in a patient with Hodgkin's
      disease, both the Hodgkin's disease and the associated neurologic syndrome were
      cured by surgical intervention and postoperative adjuvant chemotherapy. The
      patient's tumor was removed en bloc. Postoperative chemotherapy consisted of
      doxorubicin (Adriamycin), etoposide, and vinblastine. At 5-year follow-up in
      August 1996, the patient was active and tumor-free, without evidence of recurrent
      Hodgkin's disease or paraneoplastic syndrome. The possibility that this patient's
      syndrome was the result of a cross-reacting monoclonal idiotype produced by his
      tumor is suggested by the rapid recovery associated with tumor debulking. The
      role of surgery in the treatment of patients with Hodgkin's disease is limited,
      well defined, and even more infrequent in recurrent disease. Systemic
      chemotherapy is the treatment of choice for these patients, but surgery may play
      an important role in the initial cytoreduction of the recurrent tumor, especially
      in cases of localized bulky disease.

PMID- 9258314
TI  - Monoamine oxidase inhibitors and cardiac anesthesia revisited.
AB  - There are well-recognized adverse interactions between the monoamine oxidase
      inhibitors and anesthetic drugs, particularly narcotics. Patients having
      cardiopulmonary bypass procedures are commonly anesthetized using high-dose
      narcotic techniques. We describe an uneventful perioperative course in a
      parkinsonian patient who required urgent coronary artery bypass graft surgery
      while he was taking selegiline, a selective inhibitor of monoamine oxidase type
      B.

PMID- 9258316
TI  - Autoimmune progesterone dermatitis: onset in a women without previous exogenous
      progesterone exposure.
AB  - Autoimmune progesterone dermatitis is a rare clinical entity that may be seen by
      the family practitioner, gynecologist, or dermatologist. Recognition of the
      entity is paramount in the therapy of this easily treated condition. We report a
      case of a 36-year-old woman with a recurrent facial dermatitis of many months'
      duration. We found the cutaneous eruption to be temporally related to her
      menstrual cycle. The patient denied any changes in her diet, cosmetics,
      medications, or soaps that could account for the dermatitis. Despite no previous
      exposure to exogenous progesterone, the diagnosis of autoimmune progesterone
      dermatitis was made. The patient was cured by oophorectomy.

PMID- 9258317
TI  - Pulmonary blastomycosis with acute respiratory failure as predominant clinical
      feature.
AB  - Two previously healthy young adults came to our community hospital with rapidly
      progressive respiratory failure. Investigation confirmed Blastomyces as the
      responsible etiologic agent. Despite adequate antifungal chemotherapy and
      intensive supportive care, both patients died, one within 24 hours and the other
      after 14 days. Overwhelming infection with Blastomyces dermatitidis can cause
      acute respiratory failure, possibly the adult respiratory distress syndrome, even
      in immunocompetent hosts.

PMID- 9258318
TI  - Spontaneous resolution of rhodococcal pulmonary infection in a liver transplant
      recipient.
AB  - Pulmonary infection by Rhodococcus equi is characterized by indolent infection in
      an immunocompromised host with a propensity to form cavitary lesions. Mortality
      can be greater than 50%; treatment involves prolonged therapy with multiple
      antibiotics and, occasionally, surgical resection. Recurrence is common. We
      report a case of a liver transplant patient with a pulmonary nodule caused by R
      equi; the nodule followed a benign clinical course and resolved spontaneously.
      This case illustrates that the spectrum of disease caused by R equi is not fully
      appreciated and that significant pitfalls complicate the diagnosis and management
      of infection by this unusual and probably underrecognized pathogen.

PMID- 9258319
TI  - Large transitional cell carcinoma of the proximal third of the ureter in a young
      man.
AB  - We report an unusual case of a 37-year-old black man found to have a large
      transitional cell carcinoma of the proximal third of the ureter. This case is of
      interest because of the relatively young age of the patient, the upper third
      ureteral origin of the tumor, and the volume of the tumor burden.

PMID- 9258320
TI  - Posttraumatic cervical osteophytosis causing progressive dysphagia.
AB  - Dysphagia is a commonly encountered patient complaint. The differential diagnosis
      for dysphagia is extensive. One long-recognized etiology of dysphagia is cervical
      osteophytosis. Degenerative joint disease, ankylosing spondylosis, and diffuse
      idiopathic skeletal hyperostosis (DISH) can all cause cervical osteophyte
      formation. We describe a patient with dysphagia and a large cervical osteophyte.
      Our case illustrates cervical osteophytosis associated with a history of previous
      cervical spine trauma. Evaluation and management strategies are discussed.

PMID- 9258321
TI  - Pill-induced esophageal obstruction: discovery of a peptic stricture.
AB  - The patient described in this report had complete esophageal obstruction shortly
      after a new medication had been prescribed. When the obstructing pill was removed
      endoscopically, a peptic stricture was discovered. Curiously, the patient had had
      only rare transient dysphagia before this episode.

PMID- 9258322
TI  - Passive smoking exposure on submarines.

PMID- 9258323
TI  - Community-acquired pneumonia in the elderly.

PMID- 9258324
TI  - Some early stirrings (1950 ff.) of concern about environmental mutagens.

PMID- 9258325
TI  - DNA damage in nasal respiratory epithelium from children exposed to urban
      pollution.
AB  - The nasal cavity is the most common portal of entry to the human body and a well
      known target site for a wide range of air pollutants and chemically induced
      toxicity and carcinogenicity. DNA single-strand breaks (SSB) can be used as a
      biomarker of oxidant exposure and as an indicator of the carcinogenicity and
      mutagenicity of a substance. We examined the utility of using the alkaline single
      cell gel electrophoresis assay (SCGE) for measuring DNA damage in children's
      nasal epithelium exposed to air pollutants. We studied 148 children, ages 6-12,
      including 19 control children from a low polluted Pacific port and 129 children
      from Southwest Metropolitan Mexico City, an urban polluted area with high ozone
      concentrations year-round. Three sets of two nasal biopsies were taken in a 3
      month period. All exposed children had upper respiratory symptoms and DNA damage
      in their nasal cells. Eleven- and twelve-year-olds had the most DNA damage, and
      more than 30% of children aged 9-12 exhibited patchy areas of squamous metaplasia
      over high-flow nasal regions. These areas had the greatest numbers of damaged DNA
      cells (P < or = 0.001) and a large number of DNA tails > 80 microns (P < 0.001)
      when compared to the contralateral macroscopically normal site in the same child.
      The youngest children with significantly less outdoor exposure displayed patchy
      areas of goblet cell hyperplasia and had the least DNA damage. These findings
      suggest that SCGE can be used to monitor DNA damage in children's nasal
      epithelium and, further, the identification of DNA damage in nasal proliferative
      epithelium could be regarded as a sentinel lesion, most likely due to severe and
      sustained cell injury.

PMID- 9258326
TI  - Molecular analysis of mutations in T-lymphocytes from experienced Soviet
      cosmonauts.
AB  - Somatic mutation in five cosmonauts who have completed spaceflights of 7 to 365
      days was analyzed using the clonal HPRT assay. The doses received in space by the
      cosmonauts ranged from 4 to 127 mGy. hprt mutant frequencies were 2.4-5.0-fold
      higher than age-corrected values established for healthy, unexposed subjects in
      western countries [Tates et al. (1991): Mutat Res 253: 199-213; Branda et al.
      (1993): Mutat Res 285: 267-279] and 2- to 3-fold higher than those determined for
      unexposed individuals residing in Russia [Jones et al. (1995): Mutat Res 338: 129
      139]. A total of 107 collected mutant clones were analyzed by multiplex PCR. No
      excess of deletions was detected and their frequency did not correlate with
      either accumulated dose or the age of the cosmonauts. In 62 mutants cDNA was
      isolated by RT-PCR and sequenced. Those with splicing errors, as well as the
      mutants that did not produce cDNA, were further analyzed by the sequencing of
      exon(s)-containing fragments amplified from genomic DNA. The mutational spectrum
      recovered from the cosmonauts differed substantially from that of unexposed
      healthy subjects (P = 0.042), and exhibited an increased incidence of splicing
      errors, frameshifts, and complex mutations. Higher frequencies of contribution of
      AT-->GC transitions and GC-->TA transversions were also observed. The increased
      mutant frequencies and observed shifts in mutational spectra likely indicate a
      combination of potential influences, including environment, lifestyle, and
      occupational exposures. Further elucidation of these potential influences will
      require a more extensive study involving the general population sharing similar
      environment, cosmonauts in training and cosmonauts participating in space
      flights.

PMID- 9258327
TI  - A new T-lymphocyte cloning assay for detection of in vivo mutations in the human
      hypoxanthine-guanine phosphoribosyltransferase gene.
AB  - The X-linked hypoxanthine-guanine phosphoribosyl transferase (hprt) gene is a
      target of analyses of in vivo mutation frequencies in circulating T-lymphocytes.
      We established a novel, accessory cell-free cloning method of T-lymphocytes with
      a hprt mutation by a combined use of recombinant interleukin-2, conditioned
      medium from activating T-lymphocytes and culture plates coated with anti-CD3
      monoclonal antibody. Using the method, we examined mutation frequencies of the
      hprt gene in T-lymphocytes from six healthy individuals, nine patients with colon
      cancer including two patients from different families with hereditary
      nonpolyposis colon cancer and six cancer-free relatives of the patients. In six
      healthy individuals, the mean cloning efficiency and mutation frequency (MF) of
      the hprt gene in T-lymphocytes were 0.51 +/- 0.28 and 9.4 +/- 7.5 x 10(-6),
      respectively. These data were similar to the reported values. The mean MFs in the
      nine colon cancer patients (10.6 +/- 7.3 x 10(-6)) were not significantly
      different from those of the 12 cancer-free individuals (11.6 +/- 9.4 x 10(6)).
      The correlation between mutation frequencies and age of the individuals was
      significant regardless of the presence or absence of cancers. The single-strand
      conformation polymorphism analyses of nested RT-PCR products of hprt mRNA were
      done in 33 mutant clones from five members of a family of which MF values were
      high. All the analyzed mutant clones show a genetic aberration in the coding
      region of the hprt gene. At least 28 of 33 mutants were independent. Our method
      provides a new versatile tool for in vivo analysis for mutations of the hprt
      gene.

PMID- 9258328
TI  - Propylene oxide and epichlorohydrin induce DNA strand breaks in human diploid
      fibroblasts.
AB  - The induction of DNA strand breaks in human diploid fibroblasts (VH-10) was
      demonstrated after in vitro exposure with two carcinogenic epoxides, propylene
      oxide (PO) and epichlorohydrin (ECH). Alkaline DNA unwinding (ADU), pulsed field
      gel electropharosis (PFGE), and the comet assay were used to measure DNA single.
      (SSBs) and double-strand breaks (DSBs). A dose-dependent increase of DNA strand
      breaks, measured by ADU, was observed in the dose range 2.5-20 mMh of PO and 0.25
      2 mMh of ECH. The dose-response of ECH was about five times higher compared with
      that of PO (211 vs. 41 SSBs. 100 Mbp-1.mMh-1). The induction rates of DSBs,
      measured by PFGE, were found to be 18 times higher for ECH compared to PO (4.8
      and 0.27 DSBs.100 Mbp-1.mMh-1 for ECH and PO, respectively). Using these two
      methods, the SSBs/ DSBs ratio was estimated to be 148 for PO and 44 for ECH. The
      data obtained by the comet assay also demonstrated a dose-dependent ability of PO
      and ECH to induce DNA damage. It was found that ECH was about six times more
      effective as an inducer of DNA strand breaks compared to PO (200 and 32x100 Mbp
      1.mMh-1 for ECH and PO, respectively). The SSBs/DSBs ratios calculated using
      comet assay and PFGE data were 125 for ECH and 41 for PO. In addition, ECH is
      about 10 times more toxic than PO with respect to survival. These properties of
      ECH can at least in part be explained by its higher chemical reactivity connected
      with a higher rate of DNA alkylation.

PMID- 9258329
TI  - Smoking-associated mitochondrial DNA mutations in human hair follicles.
AB  - The mitochondrial DNA (mtDNA) of hair follicles was used for studying the
      genotoxicity of smoking-mediated carcinogens. We determined the incidences of the
      4,977 bp and 7,436 bp mtDNA deletions, tandem duplication in the D-loop region
      and the proportion of the 4,977 bp deleted mtDNA (dmtDNA) in the total DNA of
      hair follicles from 213 male non-smokers and 74 male smokers, respectively.
      Twenty-three patients with lung cancer were also investigated. We found that the
      current cigarette smokers had a 3.1 times higher average incidence of the 4,977
      bp dmtDNA (RR: 3.1, P < 0.001) as compared with non-smokers, and this mtDNA
      deletion was especially prevalent in the old heavy smokers. For the smokers of
      the age above 70, the average incidence of the 4,977 bp dmtDNA was 3.7 times
      higher in the group with a smoking index of 401-800 (RR: 3.7, P < 0.005) and 3.2
      times higher in the group with a smoking index greater than 800 (RR: 3.2, P <
      0.005). However, there was no statistically significant relationship between the
      incidence of the 7,436 bp dmtDNA and the smoking index, although there was a mild
      increase in the percentage of the 7,436 bp dmtDNA with the increase of the
      consumption of cigarettes. No tandem duplication of mtDNA in the D-loop region
      was disclosed in either smokers or non-smokers group. The proportions of the
      4,977 bp dmtDNA in hair follicles were found to correlate with age, but did not
      keep increasing with cigarette consumption except in the group of subjects with a
      smoking index of less than 400. On the other hand, we found that the average
      proportion of the 4,977 bp dmtDNA in the hair follicles was 1.201 +/- 0.371% for
      the patients with lung cancer who had a smoking index greater than 400, while
      that was only 0.146% for the age-matched healthy smokers with the same smoking
      index. In conclusion, the high incidence of the 4,977 bp dmtDNA of hair follicles
      is not only associated with aging but also correlated with the amount of
      cigarette smoking. A high proportion of the 4,977 bp dmtDNA in the hair follicles
      may be considered one of the molecular events that are associated with the
      occurrence of smoking-associated cancers.

PMID- 9258330
TI  - DNA adduct formation in primary mouse embryo cells induced by 7H
      dibenzo[c,g]carbazole and its organ-specific carcinogenic derivatives.
AB  - The nuclease P1 modification of the 32P-postlabeling technique was used to study
      the biological activity of 7H-dibenzo[c,g]carbazole (DBC) and some of its
      derivatives, including N-methyldibenzo[c,g]carbazole (N-MeDBC), 5,9
      dimethyldibenzo[c,g]carbazole (5,9-diMeDBC), 5,9,N-trimethyldibenzo[c,g]carbazole
      (5,9,N-triMeDBC), 6-methoxydibenzo[c,g]carbazole (6-McODBC), N
      acetyldibenzo[c,g]carbazole (N-AcDBC), N-hydroxymethyldibenzo[c,g]carbazole (N
      HMeDBC) in primary mouse embryo cells. A very good correlation was found between
      carcinogenic specificity in vivo of these N-heterocyclic aromatic hydrocarbons
      and their DNA-adduction in vitro. Primary mouse embryo cells were able to
      metabolize and detect tissue-specific sarcomagens N-MeDBC and 6-MeODBC as well as
      derivatives with both sarcomagenic and hepatocarcinogenic activity, DBC, N-AcDBC,
      and N-HMeDBC. The strong specific hepatocarcinogen 5,9-diMeDBC in vivo, did not
      induce any DNA-adducts in the embryo cells, which suggests that the enzymatic
      composition of the target tissue probably is the determining factor in the organ
      specificity of this derivative. 5,9,N-triMeDBC, derivative without any
      carcinogenic activity in vivo, did not induce any DNA-adducts in primary mouse
      embryo cells. Pretreatment of cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) apparently stimulated DNA-adduct formation in the cells exposed to DBC, 6
      MeODBC, and N-MeDBC. No or a very slight effect of TCDD on DNA-adduct formation
      was found in cells exposed to N-HMeDBC and N-AcDBC. Preliminary results have
      shown that TCDD slightly induced cytochrome P4501A1-linked ethoxyresorufin O
      deethylase (EROD) activity in primary mouse embryo cells. These data suggest the
      role of cytochrome P4501A1 in the metabolism of DBC derivatives with sarcomagenic
      activity.

PMID- 9258332
TI  - Identification and expression of uvi31+, a UV-inducible gene from
      Schizosaccharomyces pombe.
AB  - The Schizosaccharomyces pombe uvi31+ gene has been previously isolated as a UV
      inducible gene [Lee JK et al. (1994) Biochem Biophys Res Commun 202:1113-1119].
      This gene encodes a protein of about 12 kDa with 57% amino acid sequence
      similarity to Escherichia coli BolA protein which is known to be involved in
      switching between the cell elongation and septation systems during the cell
      division cycle. The putative Mlul cell cycle box (MCB), SWI4/6-dependent cell
      cycle box (SCB), and gear-box elements are found in the upstream region of uvi31+
      gene, suggesting that this gene shows the cell cycle-regulated and growth phase
      dependent expression. Interestingly, the level of uvi31+ transcript varies
      throughout the cell cycle, peaking in G1 phase before septation, and also shows
      the growth phase-dependent pattern during cellular growth, increasing maximally
      at the diauxic shift phase just before stationary phase. Furthermore, the
      transcript level of this gene is raised after S phase arrest, and is also
      increased maximally at 4 hr after UV irradiation of 240 J/m2. These results
      suggest that the delayed induction of uvi31+ gene after UV irradiation may be
      caused by cell cycle control of this gene after DNA replication checkpoint
      arrest. Thus, the uvi31+ gene may play a role in controlling the progress of the
      cell cycle after DNA damage (UV irradiation).

PMID- 9258331
TI  - Mutational specificity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in
      Escherichia coli: comparison of in vivo with in vitro exposure of the supF gene.
AB  - Forward mutations induced by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)
      in the supF gene of Escherichia coli were recovered from bacteria deficient in
      nucleotide excision repair and in DNA-alkyltransferase activity. Bacteria were
      exposed to 0.4 mM CCNU (in vivo supF mutagenesis), increasing the overall
      mutation frequency 15.7-fold above the spontaneous value. A total of 73
      independent supF- mutants were sequenced. The resulting mutation spectrum was
      compared with those obtained in bacteria and mammalian cells following the
      classical shuttle-vector approach (in vitro supF mutagenesis). In vivo CCNU
      mutagenesis in E. coli yielded a large number of deletions (20/73), in agreement
      with mammalian data but distinct from in vitro bacterial spectra, which are
      almost exclusively composed of G:C-->A:T transitions. A substantial proportion
      (6/18) of CCNU-induced deletions (> 3 bp) involved repeated DNA sequences,
      suggesting a contribution of a slippage-misalignment process in the generation of
      this mutation class. Substitutions occurred primarily at G:C base pairs (44/53)
      and were predominantly G:C-->A:T transitions (39/53). This mutational change was
      attributed to the mispair potential of the O6-chloroethylguanine lesion with
      thymine. Most G:C-->A:T transitions (34/39) were located at three 5'-GG-3'
      hotspot sites (positions 123, 160, and 168). The distribution of hotspot sites
      for G:C-->A:T substitutions differed as a function of the in vivo or in vitro
      chemical modification of the supF-bearing plasmids and revealed significant
      differences in the DNA strand distribution of this mutational event. Our data
      suggest that the transcriptional status of the target gene has strong influence
      on the probability of O6-chloroethylguanine formation, reducing its incidence in
      the transcribed DNA strand.

PMID- 9258333
TI  - Nereis virens (Annelida: Polychaeta) is not an adequate sentinel species to
      assess the genotoxic risk (comet assay) of PAH exposure to the environment.
AB  - Polychaetes, because of their bioturbation capacity, play an important role in
      the distribution of anthropogenic contaminants (including polycyclic aromatic
      hydrocarbons [PAHs]) throughout the sediments. In this work the use of Nereis
      virens (Annelida: Polychaeta) as a bioindicator to assess the genotoxic risk of
      PAH exposure for the environment was evaluated. For this purpose the alkaline
      single cell gel electrophoresis [comet] assay was applied on the coelomocytes of
      in vivo exposed Nereis virens. Benzo[a]pyrene (B[a]P) was chosen because it is
      classified by the IARC (International Agency for Research on Cancer) as "probably
      carcinogenic to humans" and because its mechanisms of action are well-known.
      Nereis virens was exposed to B[a]P in concentrations of 0.3, 0.6, 10, 20, 35 and
      45 mg/ml by an intracoelomic injection of B[a]P (20 microliters) dissolved in
      dimethyl sulphoxide (DMSO). A solvent control with DMSO, a positive control with
      ethyl methane sulphonate (EMS) (12.1 mg/ml) and a negative control were included
      in each experiment. For each treatment four animals were analysed. After 1 hr
      treatment coelomocytes were harvested by puncturing the coelomic cavity with a
      sharpened Pasteur pipette, mixed with 0.5% low melting point agarose and
      sandwiched between two other gel layers. Ethidium bromide stained nuclei were
      analysed for tail length and tail moment. 12.1 mg/ml EMS, pure DMSO (98.9%) and
      B[a]P in all tested concentrations induced a statistically significant increase
      of DNA single strand breaks in the comet assay. The effect of B[a]P, however, was
      only at the highest concentration (45 mg/ml) significantly stronger than the
      effect of DMSO alone. Although a relatively large heterogeneity in the results
      could be observed, these experiments clearly showed that Nereis virens is not
      suited as a sentinel species for the assessment of the genotoxic risk of PAH
      exposure because this species seems to be very resistant to benzo[a]pyrene.

PMID- 9258334
TI  - Tobacco cotyledons: a novel system for testing mutagenicity in plants.

PMID- 9258335
TI  - Induction in human osteoblastic cells (SaOS2) of the early response genes fos,
      jun, and myc by the amino terminal fragment (ATF) of urokinase.
AB  - Previous studies have demonstrated that overexpression of urinary plasminogen
      activator (uPA) in rat prostate cancer cells results in increased skeletal
      metastases, which are primarily of the osteoblastic variety. The osseous
      activation induced by the metastases appears to be mediated through the amino
      terminal fragment (ATF) of uPA, which lacks the catalytic domain and can act as a
      growth factor for osteoblasts. To explore further the mechanism of action of uPA
      in bone cells, we evaluated the effects of ATF on modulating the expression of
      various proto-oncogenes. Human-osteoblast-derived osteosarcoma cells, SaOS2, were
      treated with graded doses of ATF for 10-120 min, and effects on early response
      proto-oncogenes were monitored. ATF increased c-myc, c-jun, and c-fos gene
      expression in a time-dependent manner for up to 60 min, after which mRNA levels
      fell. The maximum induction was seen in c-fos gene expression, which was found to
      be dose dependent. This effect of ATF was localized to its growth-factorlike
      domain. Examination of the half life of these transcripts in the presence of the
      transcriptional inhibitor actinomycin D demonstrated that ATF does not alter the
      stability of c-fos mRNA in these bone cells. Nuclear run-off assays indicated
      that ATF effects were due to stimulation of c-fos gene transcription. An increase
      in c-fos protein levels was correlated with the augmentation of its mRNA in ATF
      treated SaOS2 cells. Pretreatment of SaOS2 cells with the protein tyrosine kinase
      inhibitor herbimycin and recombinant soluble uPA receptor (uPAR) caused a
      significant reduction in the ability of ATF to induce c-fos expression. These
      results demonstrate a novel role for uPA in activating early response proto
      oncogenes, in particular c-fos, which plays an important role in bone cell growth
      and differentiation and may be a key factor in the signal transduction pathway of
      ATF.

PMID- 9258337
TI  - Apoptosis of W256 carcinosarcoma cells of the monocytoid origin induced by NDGA
      involves lipid peroxidation and depletion of GSH: role of 12-lipoxygenase in
      regulating tumor cell survival.
AB  - Arachidonate lipoxygenases (LOX) and their products play an important role in
      mediating growth factor-supported tumor cell proliferation and growth. The LOX
      pathway may also be critical in regulating tumor cell survival and apoptosis.
      Blocking the 12-LOX gene expression with sequence-specific antisense oligos or
      its activity with general or isoform-specific LOX inhibitors induces a strong
      apoptotic response in rat W256 carcinosarcoma cells of the monocytoid origin
      (Tang et al., 1996, Proc. Natl. Acad. Sci. U.S.A., 93:5241-5246). In the present
      study, several molecular approaches confirmed the predominant expression of
      platelet-type 12-LOX in W256 cells, with no or little expression of 5- and 15
      LOX. NDGA, a general LOX inhibitor and BHPP, a 12-LOX-selective inhibitor,
      induced rapid and dose-dependent apoptosis of serum-cultured W256 cells as well
      as several other tumor (in particular leukemia) cell lines, thus suggesting a
      potential role for LOX in mediating serum-supported tumor cell survival. The
      molecular mechanism of NDGA-induced W256 cell death was subsequently
      investigated. NDGA-induced apoptosis could be significantly postponed by
      overexpression of 12-LOX, thus suggesting that the NDGA effect is, at least
      partly, dependent on its inhibition of LOX (i.e., 12-LOX). W256 cell apoptosis
      induced by NDGA could also be effectively inhibited by GSH-elevating or thiol
      agents as well as by lipid peroxidation inhibitors and an inhibitor of
      mitochondria respiratory chain rotenone. Further experiments demonstrated that
      NDGA treatment triggered rapid lipid peroxidation leading to the depletion of
      cytosolic and mitochondrial GSH pools. Interestingly, the lipid peroxidation
      induced by NDGA could not be inhibited by conventional free radical scavengers
      nor by cyclooxygenase or cytochrome P-450 monooxygenase inhibitors. In summary,
      the present work suggests a role of 12-LOX in regulating serum (growth factor)
      supported survival of certain tumor cells.

PMID- 9258336
TI  - Decrease of Ca(2+)-ATPase activity in human keratinocytes during calcium-induced
      differentiation.
AB  - Ca2+ regulates keratinocyte differentiation by increasing intracellular Ca2+
      levels. Ca(2+)-ATPase in the Ca(2+)-induced differentiation of human
      keratinocytes was investigated by measuring Ca(2+)-ATPase mRNA, protein, and
      activity levels. Human keratinocytes were grown in Keratinocyte Growth Medium
      containing 0.03, 0.1, or 1.2 mM Ca2+ and assayed on days 2, 5, 7, 14, and 21.
      Ca(2+)-ATPase mRNA levels were found to be modestly increased in 5-, 7-, and 14
      day cultured cells as compared with 2-day cultured cells, but levels fell below
      that of the 2-day cultured cells in the 21-day cultured cells. The Ca(2+)-ATPase
      mRNA levels were not affected by Ca2+ levels. A 135-kDa protein in human
      keratinocytes cross reacted with the monoclonal antibody against human
      erythrocyte Ca(2+)-ATPase. The level of this protein was decreased by Ca2+ and
      lost during differentiation, in parallel with the loss of enzymatic activity.
      Ca2+ influx of postconfluent 1.2 mM Ca(2+)-grown cells was higher than that of
      cells grown in lower Ca2+ concentrations. Ca2+ efflux from postconfluent cells
      grown in 0.03 mM Ca2+ was less than that from cells grown in stronger Ca2+
      concentrations. These results suggest that the loss of the plasma membrane Ca(2+)
      ATPase with time in culture contributes to the rise in intracellular Ca2+, thus
      promoting keratinocyte differentiation.

PMID- 9258338
TI  - A novel anti-inflammatory peptide inhibits endothelial cell cytoskeletal
      rearrangement, nitric oxide synthase translocation, and paracellular permeability
      increases.
AB  - The endothelial cell (EC) membrane-cytoskeletal interface in part maintains
      plasma membrane integrity and promotes cell-cell apposition. Nonmuscle filamin
      (ABP-280), an actin crosslinking protein, promotes orthogonal branching of F
      actin and is the major protein that links the peripheral actin network to the
      plasma membrane through its C-terminal glycoprotein binding site. In response to
      bradykinin, filamin translocates from the cell periphery to the cytosol within 1
      min. A synthetic peptide, corresponding to filamin's C-terminal
      calcium/calmodulin-dependent protein kinase II phosphorylation site (CaM
      peptide), prevents calcium-activated filamin translocation in permeabilized
      bovine pulmonary artery EC. The myristoylated permeable form of this peptide
      inhibits bradykinin-induced filamin translocation and F-actin rearrangement in
      cultured intact ECs. In addition, bradykinin-induced paracellular gap formation
      is significantly attenuated by CaM peptide, which suggests that the presence of a
      filamin-based peripheral F-actin network is essential for maintaining EC barrier
      function. Moreover, CaM peptide reduces wound-induced EC migration rate by 40%,
      which indicates that F-actin rearrangement is required for efficient cell
      motility. The CaM peptide affects other bradykinin-induced inflammatory
      responses. EC nitric oxide synthase (eNOS) translocates from the cell membrane to
      the nuclear fraction within 1-2 min of bradykinin treatment. Pretreatment with
      CaM peptide inhibits eNOS translocation. However, the peptide has no effect on
      bradykinin-induced von Willebrand Factor release. In summary, the CaM peptide
      exhibits several anti-inflammatory properties that include maintaining EC
      junctional stability and inhibiting eNOS translocation.

PMID- 9258339
TI  - Nitric oxide attenuates cellular hexose monophosphate shunt response to oxidants
      in articular chondrocytes and acts to promote oxidant injury.
AB  - Nitric oxide (NO) has been implicated in both cartilage degradation and cell
      survival. Importantly, NO has been shown, in a cell-type-dependent manner, to
      directly cause cell death or indirectly promote cell death by compromising the
      ability of cells to detoxify intra- or extracellular oxidants. In this study we
      examined the role of NO in the survival of bovine chondrocytes exposed to
      catabolic cytokines (interleukin-1 (IL-1); tumor necrosis factor [TNF]) with or
      without the addition of an exogenous oxidant stress (e.g., H2O2, HOOCl, etc.).
      The exposure of chondrocytes to a mixture of IL-1 and TNF (IL-1/TNF) results in
      the release of NO but did not alter cell viability. However, there was evidence
      of NO-dependent oxidative responses in the IL-1/TNF group, as we observed an
      increased level of intracellular oxidants as well as the appearance of a 55 kD
      nitrated protein which reflects the formation of peroxynitrite. We next analyzed
      viability with H2O2. The LD50 for IL-1/TNF-treated cells was 0.1 mM (vs. 1 mM for
      control). The enhanced sensitivity was completely reversed when cells were
      incubated with the NO synthase inhibitor 1-n5-1-iminoethylornithine (NIO). To
      test whether cell death was caused by compromising the ability of cells to
      detoxify extracellular oxidants, we examined the hexose monophosphate shunt
      (HMPS) response in cells given H2O2. Treatment of control cells with H2O2
      resulted in a fourfold increase in HMPS activity. In contrast, IL-1/TNF cells
      exhibited no increase in HMPS activity. The attenuation of stimulated HMPS
      activity was reversed by the coaddition of NIO. Thus, these data indicate that 1)
      endogenous NO mediates cytokine-dependent susceptibility to oxidant injury and 2)
      this effect is in part due to impaired activation of the HMPS. In inflamed joints
      replete with cytokines and oxidants, NO may contribute to chondrocyte death and
      progressive joint destruction.

PMID- 9258341
TI  - Restored expression of transforming growth factor beta type II receptor in k-ras
      transformed thyroid cells, TGF beta-resistant, reverts their malignant phenotype.
AB  - Transforming growth factor beta 1 (TGF beta 1) inhibits the growth of normal rat
      epithelial thyroid cells (FRTL-5 strain) by counteracting thyrotropin (TSH)
      stimulated DNA synthesis and by slowing the cells in the G1 phase of the cell
      cycle. Here, we have studied two clones of FRTL-5 thyroid cell line transformed
      by the wild type (wt) v-k-ras oncogene (K.M.A1, K.M.A2) and one clone (A6)
      transformed by a temperature-sensitive (ts) v-k-ras mutant. Anchorage-dependent
      as well as anchorage-independent growth of these k-ras-transformed cells was not
      inhibited by TGF beta 1. TGF beta 1 resistance appeared to be dependent by a
      functional p21 k-ras, because A6 cell growth was partially inhibited at the
      nonpermissive temperature (39 degrees C). To determine the basis for TGF beta 1
      resistance in k-ras-transformed thyroid cells, we looked for possible defects in
      the expression of type I (T beta R-I/ALK5) and type II TGF beta receptors (T beta
      R-II). Lower levels of type II receptors were present in all of the k-ras
      transformed clones, as revealed by both Northern blot and cross-linking
      experiments. A partial reversion of the malignant phenotype of the wt k-ras
      transformed clone was obtained in two clones isolated after transfection of the
      malignant thyroid cells (K.M.A1) with a T beta R-II expression vector. These two
      clones also showed restored levels of exogenous T beta R-II mRNA and protein, and
      both clones showed a partially reacquired sensitivity to TGF beta 1. Similarly,
      the reversion of the malignant phenotype of the A6 clone grown at the
      nonpermissive temperature was accompanied by a restored expression of the T beta
      R-II receptors. These data indicate that active k-ras oncogene can induce TGF
      beta 1 resistance in rat thyroid cells and suggest that one of the possible
      mechanisms of escape from TGF beta 1 growth control in k-ras-induced thyroid
      carcinogenesis involves a reduced expression of T beta R-II receptors.

PMID- 9258340
TI  - Cytoskeleton regulates expression of genes for transforming growth factor-beta 1
      and extracellular matrix proteins in dermal fibroblasts.
AB  - Cytoskeleton not only controls cell morphology but also regulates cell growth,
      migration, differentiation, and gene expression, events which are fundamental to
      embryogenesis, carcinogenesis, and wound healing. We have recently reported that
      reorganization of cytoskeleton induces expression of mRNA for transforming growth
      factor-beta 1 (TGF-beta 1), collagenase, and tissue inhibitor of
      metalloproteinase-I (TIMP-I) in dermal fibroblasts. In this report we have
      examined the role of gene transcription in this induction. As judged by nuclear
      run-on assay, trypsin, EGTA (ethylene glycol-bis (beta-aminoethyl ether) N, N,
      N', N', tetra-acetic acid), or cytochalasin C (Chs) increased the rate of
      transcription of the TGF-beta 1 gene by 2.0, 2.7, and 1.6 fold, respectively, and
      of the collagenase gene by 5.3, 6.2, and 3.3 fold. The rate of transcription of
      the TIMP-I gene was increased by trypsin (4.3 fold) or EGTA (3.8 fold) but
      unaffected by Chs. Cytochalasin induced an increase in the rate of transcription
      of procollagen I (alpha 1), procollagen I (alpha 2), and fibronectin genes by
      1.4, 1.5, and 1.9 fold respectively, while trypsinization or EGTA treatment had
      no or little effects on these gene. Since transcription of the TGF-beta 1 gene is
      believed to be largely governed by the activating protein 1 (AP1) complex, we
      also examined the expression of mRNA for c-fos and c-jun protoon-coproteins.
      Trypsinization induced rapid (within 30 min) and transient expression of c-fos
      mRNA. A 2.4 fold increase in c-jun mRNA was apparent after 4 hr and persisted for
      at least 24 hr. Actinomycin D (Act D) suppressed the induction of TGF-beta 1 mRNA
      by Chs but had less effect on the TGF-beta 1 mRNA in trypsinized cells which had
      been replated for 4 hr, suggesting that the half life of TGF-beta 1 mRNA is
      reduced in cells with a disassembled cytoskeleton. Simultaneous treatment with
      Chs and cycloheximide (Cxm) resulted in a superinduction of TGF-beta 1 mRNA by 88
      +/- 23% (n = 4, P < 0.05), which was abrogated by preexposure to Act D. In
      contrast, the induction of collagenase mRNA by Chs was totally blocked by Cxm,
      indicating that the Cxm-mediated superinduction is selective and that protein
      synthesis is required for induction of this mRNA. Our results suggest that the
      activities of genes for proteins involved in the structure (Type I collagen and
      fibronectin), turnover (collagenase and TIMP-1) and regulation (TGF-beta 1) of
      extracellular matrix (ECM), are all governed at least in part by the status of
      the cytoskeleton. Since the cytoskeleton is reorganized during cell division,
      migration, and differentiation, these results may have implications for the
      regulation of ECM during such processes as embryogenesis, carcinogenesis, and
      wound healing.

PMID- 9258342
TI  - Endothelial proteoglycans inhibit bFGF binding and mitogenesis.
AB  - Basic fibroblast growth factor (bFGF) is a known mitogen for vascular smooth
      muscle cells and has been implicated as having a role in a number of
      proliferative vascular disorders. Binding of bFGF to heparin or heparan sulfate
      has been demonstrated to both stimulate and inhibit growth factor activity. The
      activity, towards bFGF, of heparan sulfate proteoglycans present within the
      vascular system is likely related to the chemical characteristics of the
      glycosaminoglycan as well as the structure and pericellular location of the
      intact proteoglycans. We have previously shown that endothelial conditioned
      medium inhibits both bFGF binding to vascular smooth muscle cells and bFGF
      stimulated cell proliferation in vitro. In the present study, we have isolated
      proteoglycans from endothelial cell conditioned medium and demonstrated that they
      are responsible for the bFGF inhibitory activity. We further separated
      endothelial secreted proteoglycans into two fractions, PG-A and PG-B. The large
      sized fraction (PG-A) had greater inhibitory activity than did PG-B for both bFGF
      binding and bFGF stimulation of vascular smooth muscle cell proliferation. The
      increased relative activity of PG-A was attributed, in part, to larger heparan
      sulfate chains which were more potent inhibitors of bFGF binding than the smaller
      heparan sulfate chains on PG-B. Both proteoglycan fractions contained perlecan
      like core proteins; however, PG-A contained an additional core protein
      (approximately 190 kDa) that was not observed in PG-B. Both proteoglycan
      fractions bound bFGF directly, and PG-A bound a significantly greater relative
      amount of bFGF than did PG-B. Thus the ability of endothelial heparan sulfate
      proteoglycans to bind bFGF and prevent its association with vascular smooth
      muscle cells appears essential for inhibition of bFGF-induced mitogenesis. The
      production of potent bFGF inhibitory heparan sulfate proteoglycans by endothelial
      cells might contribute to the maintenance of vascular homeostasis.

PMID- 9258343
TI  - 1,25-Dihydroxyvitamin D3 selectively induces increased expression of the Na,K
      ATPase beta 1 subunit in avian myelomonocytic cells without a concomitant change
      in Na,K-ATPase activity.
AB  - Treatment of avian myelomonocytic cells with 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) results in an approximately two fold increase in levels of Na,K
      ATPase beta 1 subunit mRNA and protein (both total and plasma membrane
      associated). The changes in beta 1 subunit expression occur in the absence of a
      detectable increase in expression of any of the three alpha subunit isoforms or
      in Na,K-ATPase activity. The selective induction of the expression of the beta
      subunit in avian myelomonocytic cells by 1,25(OH)2D3 reveals a previously
      unobserved feature of the regulation of Na,K-ATPase expression, while the
      targeting of beta subunit polypeptides to the plasma membrane in the absence of a
      corresponding increase in active Na,K-ATPase suggests that, in these cells,
      transport of the beta subunit to the plasma membrane may be independent of its
      binding to the alpha subunit.

PMID- 9258344
TI  - Phosphatidylinositol-3 kinase is involved in ruffled border formation in
      osteoclasts.
AB  - Phosphatidylinositol (PI)-3 kinase has been implicated in several aspects of
      intracellular membrane trafficking, although the detailed mechanism is yet to be
      established. We previously reported that wortmannin (WT), a selective inhibitor
      of PI-3 kinase, inhibited the bone-resorbing activity of osteoclasts (Nakamura et
      al., 1995, FEBS Lett., 361:79-84). In this study, we examined how PI-3 kinase was
      involved in membrane trafficking in osteoclasts which are primary bone-resorbing
      cells. Osteoclasts exhibit a highly polarized cytoplasmic organization, the
      ruffled border. Ruffled borders are formed by numerous deep membrane
      invaginations, on which vacuolar H(+)-ATPase (V-ATPase) is localized in a high
      density. Immunoelectron microscopic analyses revealed that PI-3 kinase was
      specifically present along ruffled border membranes and the limiting membranes of
      associated intracellular vacuoles in rat authentic osteoclasts. WT and LY294002,
      another inhibitor of PI-3 kinase, caused the accumulation of numerous acidic
      vacuoles which were stained with acridine orange in murine osteoclast-like
      multinucleated cells formed in vitro. An electron microscopic examination showed
      that these vacuoles contained V-ATPase along their limiting membranes and
      appeared to be derived from the Golgi apparatus as ruffled border precursors. A
      time course study revealed that WT-induced vacuoles began to accumulate in the
      region close to the apical membrane and were finally distributed throughout the
      cytoplasm. Removal of WT from the culture medium resulted in the disappearance of
      vacuoles in the cytoplasm, leading to the formation of ruffled borders. During
      the culture period, some vacuoles were observed to fuse with the ruffled border
      membrane. A pit formation assay on dentine slices also showed that the pit
      forming activity of osteoclast-like cells was recovered by the removal of WT from
      the assay. These results suggest that PI-3 kinase plays an important role in
      ruffled border formation in osteoclasts, probably in the fusion of membrane
      vacuoles with the plasma membrane.

PMID- 9258345
TI  - Moloney murine leukemia virus long terminal repeat activates monocyte chemotactic
      protein-1 protein expression and chemotactic activity.
AB  - Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic
      retrovirus which causes T lymphomas. Recently, Mo-MuLV has been shown to trans
      activate cellular genes. Monocyte chemoattractant protein-1 (MCP-1) is a
      chemokine which can promote the migration and diapedesis of monocytes and
      lymphocytes, as well as inducing metastasis of lymphomas. Here we demonstrate
      that introduction of Mo-MuLV or the MuLV LTR alone, transiently or stably, into
      Balb/c-3T3 cells or HeLa cells resulted in 9-11 fold increases in MCP-1
      transcripts. This trans-activation of the MCP-1 gene by the Mo-MuLV LTR is
      independent of the physical location of the MCP-1 gene or of the LTR, occurring
      whether the LTR or the MCP-1 gene is integrated in the genome or transiently
      expressed. Immunoblot analysis using an anti-MCP-1 polyclonal antibody showed
      that the expression of the MuLV LTR in HeLa cells also induced the appearance of
      the MCP-1 protein. Boyden Chamber analysis demonstrated that the MCP-1
      chemotactic activity produced by HeLa cells with an integrated MuLV LTR was
      elevated by 11 fold and that neutralizing antibody to human MCP-1 abrogated
      monocyte migration in response to MuLV LTR expression. Promoter deletional
      analysis showed the LTR responsive cis-acting element in the MCP-1 promoter is
      located between -141 and -88. Deletion of this region abolished the trans
      activation of MCP-1 by the LTR. These LTR-mediated activations of a chemotactic
      and inflammatory cytokine may be relevant as mechanisms whereby retroviruses
      which do not contain oncogenes can induce neoplasia.

PMID- 9258346
TI  - Retinoic acid regulates the expression of insulin-like growth factors I and II in
      osteoblasts.
AB  - Insulin-like growth factors (IGF) I and II are the most abundant growth factors
      secreted by skeletal cells, and retinoic acid has many important action on cell
      differentiation and osteoblastic function. Some of these actions may be mediated
      by changes in the expression of IGF I and II since IGFs are known to enhance the
      differentiated function of the osteoblast. We examined the effects of all
      transretinoic acid on IGF I and IGF II expression in cultures of osteoblast
      enriched cells from 22 day fetal rat calvariae (Ob cells). Retinoic acid caused a
      transient increase in IGF I and IGF II mRNA levels after 6 h, but after 24 and 48
      h of treatment a dose-dependent decrease was observed. Cycloheximide prevented
      the inhibitory effect of retinoic acid. Retinoic acid treatment for 48 h
      decreased IGF I polypeptide levels in the culture medium. In contrast, 48 h
      exposure to retinoic acid increased IGF II polypeptide levels, possible due to
      increased levels of IGF binding protein-6. The decay of IGF I and II mRNA in
      transcriptionally arrested Ob cells was similar in control and retinoic acid
      treated cells. After 2 h, retinoic acid increased the rates of IGF I and II
      transcription, as determined by a nuclear run-on assay and heterogeneous nuclear
      RNA levels, but after 24 h retinoic acid was inhibitory. Retinoic acid had
      opposite effects to IGFs in osteoblasts and inhibited DNA and collagen synthesis.
      In conclusion, following a small transient increase, retinoic acid causes a
      pronounced decrease in IGF I and IGF II mRNA expression in Ob cells. However,
      treatment with retinoic acid causes a decrease in IGF I and an increase in IGF II
      polypeptide levels. These changes in the IGF/IGFBP axis may be relevant to the
      mechanism of action of retinoic acid in bone.

PMID- 9258347
TI  - CDC2-related kinase PITALRE phosphorylates pRb exclusively on serine and is
      widely expressed in human tissues.
AB  - Mammalian cell cycle progression is regulated by sequential activation and
      inactivation of cyclin-dependent kinases (cdks). Recently, several new members of
      the cdk family were cloned, and some of these were shown to complex with
      different cyclins and to be active at discrete stages of the cell cycle. PITALRE,
      a new member of this family, was cloned by our laboratory and was shown to be
      able to phosphorylate pRb protein in vitro. In the current work, we found that
      PITALRE kinase activity phosphorylated pRb at sites similar to those
      phosphorylated by the CDC2 kinase, which itself is known to mimic, in vitro, the
      in vivo phosphorylation of pRb. Phosphorylation of pRb by the PITALRE-associated
      kinase activity was on Ser residues exclusively. Moreover, we investigated the
      expression pattern of PITALRE in normal human tissues, using immunohistochemical
      techniques so as to gain additional data on the characteristics of this new cdk
      family member. The protein was widely expressed, although a different tissue
      distribution and/or level of expression was found in various organs. Some
      specialized tissues such as blood, lymphoid tissue, ovarian cells, and the
      endocrine portion of the pancreas showed a high expression level of PITALRE. The
      specific expression pattern found suggests that PITALRE may be involved in
      specialized functions in certain cell types.

PMID- 9258348
TI  - Synthesis and biology of a 7-nitro-2,1,3-benzoxadiazol-4-yl derivative of 2
      phenylindole-3-acetamide: a fluorescent probe for the peripheral-type
      benzodiazepine receptor.

PMID- 9258350
TI  - Identification of highly potent retinoic acid receptor alpha-selective
      antagonists.
AB  - The syntheses and full retinoid receptor characterization of a novel series of
      retinoic acid receptor alpha (RAR alpha) antagonists, 1-5, are described. These
      compounds bind with high affinity to RAR alpha but were completely inactive in
      gene transactivation. They were also potent and effective antagonists of retinoic
      acid (RA) induced gene transcription at RAR alpha. Compounds 1-5 exhibited
      varying degrees of selectivity for RAR alpha relative to RAR beta/gamma, with
      compound 5 being the most selective in both binding and functional antagonism
      assays. These compounds will be invaluable tools in delineating the physiological
      roles of RAR alpha in development and in the adult animal and may themselves be
      useful therapeutic agents in human diseases associated with RAR alpha.

PMID- 9258349
TI  - An orally bioavailable pyrrolinone inhibitor of HIV-1 protease: computational
      analysis and X-ray crystal structure of the enzyme complex.

PMID- 9258351
TI  - Doxoform and Daunoform: anthracycline-formaldehyde conjugates toxic to resistant
      tumor cells.
AB  - The recent discovery that the clinically important antitumor drugs doxorubicin
      and daunorubicin alkylate DNA via catalytic production of formaldehyde prompted
      the synthesis of derivatives bearing formaldehyde. Reaction of the parent drugs
      with aqueous formaldehyde at pH 6 produced in 40-50% yield conjugates consisting
      of two molecules of the parent drug as oxazolidine derivatives bound together at
      their 3'-nitrogens by a methylene group. The structures were established as
      bis(3'-N-(3'-N,4'-O-methylenedoxorubicinyl)) methane (Doxoform) and bis(3'-N-(3'
      N,4'-O-methylenedaunorubicinyl))methane (Daunoform) from spectroscopic data. Both
      derivatives are labile with respect to hydrolysis to the parent drugs. 3'-N,4'-O
      Methylenedoxorubicin and 3'-N,4'-O-methylenedaunorubicin are intermediates in the
      hydrolysis. Daunoform reacts with the self-complementary deoxyoligonucleotide
      (GC)4 faster than the combination of daunorubicin and formaldehyde at an
      equivalent concentration to given drug-DNA adducts. In spite of hydrolytic
      instability, Doxoform is 150-fold more toxic to MCF-7 human breast cancer cells
      and 10000-fold more toxic to MCF-7/ADR resistant cells. Toxicity to resistant
      cancer cells is interpreted in terms of higher lipophilicity of the derivatives
      and circumvention of catalytic formaldehyde production.

PMID- 9258352
TI  - Anti-Helicobacter pylori agents. 1. 2-(Alkylguanidino)-4-furylthiazoles and
      related compounds.
AB  - A series of 2-(alkylguanidino)-4-[5-(acetamidomethyl)furan-2-yl]thiazoles and
      related compounds were synthesized and evaluated for antimicrobial activity
      against Helicobacter pylori, inhibitory effect on gastric acid secretion, and
      histamine H2-receptor antagonist activity. Introduction of alkyl substituents on
      the guanidino moiety resulted in a significant increase in antimicrobial
      activity, which was associated with the alkyl chain length. Of the compounds
      obtained, the n-hexylguanidino derivative 13 demonstrated a 250-fold improvement
      in activity (MIC = 0.11 micrograms/mL) over the unsubstituted guanidino
      derivative 7. Alkyl-substituted guanidino derivatives also displayed gastric
      antisecretion and H2-antagonist activities. However, a simple correlation between
      the alkyl chain length and the activities was not found in these assays.
      Replacement of the guanidine with other bioisosteric groups (thiourea, urea, or
      (dimethylamino)methyl) resulted in loss of all activities tested. Thus the
      guanidino moiety was found to be essential for activity in this series of
      compounds.

PMID- 9258353
TI  - Selective inhibitors of monoamine oxidase. 4. SAR of tricyclic N
      methylcarboxamides and congeners binding at the tricyclics' hydrophilic binding
      site.
AB  - Linear [6.6.6] tricyclic moieties whose center ring is made of two atoms of
      differing size (here primarily thioxanth-9-ones and phenoxathiins)
      monosubstituted meta to the sulfur by C(O)NHMe include potent and selective
      inhibitors of monoamine oxidase A. Similarities with effects on SAR of acylamide
      and of diazapentacyclic substitution on such rings, including positional
      variables, the requirement for monomethylation (primary and dialkylated amides
      are inactive and higher monoalkylated amides show little or no potency), and that
      sulfur is optimally in sulfone form, suggest that binding to the enzyme occurs
      similarly in each series. No significantly greater rise in blood pressure was
      found in rats given sufficient 8 to inhibit most brain and liver MAO A and then
      followed by oral tyramine than was found on administration of tyramine to
      controls. This is in contrast to a large blood pressure rise in rats pretreated
      with phenelzine followed by tyramine, and in accord with the belief that an
      inhibitor selective for MAO A which is reversibly bound to the enzyme and
      therefore displaced by any ingested tyramine will not lead to the "cheese effect"
      (hypertension during treatment with MAO inhibitors usually caused by ingestion of
      foods containing tyramine).

PMID- 9258354
TI  - Synthesis and ligand binding studies of 4'-iodobenzoyl esters of tropanes and
      piperidines at the dopamine transporter.
AB  - Four analogs and two homologs of cocaine, designed as potent cocaine antagonists,
      were synthesized. The SN2 reaction between ecgonine methyl ester (13) or
      appropriately substituted piperidinol (19, 21) and appropriately substituted 4
      iodobenzoyl chloride gave 4-iodobenzoyl esters of tropanes and piperidines (5-8).
      2'-Hydroxycocaine (9) was obtained from 2'-acetoxycocaine (12) by selective
      transesterification with MeOH saturated with dry HCl gas. 2'-Acetoxycocaine (12)
      was synthesized from acetylsalicyloyl chloride (23) and ecgonine methyl ester
      (13). The binding affinities of these compounds were determined at the dopamine
      transporter for the displacement of [3H]WIN-35428. An iodo group substitution at
      the 4'-position of cocaine decreased dopamine transporter binding potency, while
      a hydroxy or acetoxy group at the 2'-position exhibited increased binding potency
      for the dopamine transporter compared to cocaine (10- and 3.58-fold,
      respectively). 2'-Hydroxylation also enhanced the bidning potency of 4'
      iodococaine (5) by 10-fold. Replacement of the tropane ring with piperidine led
      to poor binding affinities.

PMID- 9258355
TI  - Synthesis and in vitro activity of long-chain 5'-O-[(alkoxycarbonyl)phosphinyl]
      3'-azido-3'-deoxythymidines against wild-type and AZT- and foscarnet-resistant
      strains of HIV-1.
AB  - Lipophilic esters of 3'-azido-3'-deoxy-5'-O-(carboxyphosphinyl)thymidine (PFA
      AZT) were synthesized and tested for antiretroviral activity in CD4+ HT4-6C cells
      infected with either wild-type HIV-1LAI, a PFA-resistant strain encoding a single
      point mutation in reverse transcriptase (E89K), or an AZT-resistant clinical
      isolate (A018-post). Arbuzov condensation of 1-octadecyl, 1-eicosanyl, and 1
      docosanyl chloroformate with trimethyl phosphite yielded the corresponding
      dimethyl long-chain alkyl triesters of PFA. Selective removal of one methyl group
      from the triesters with sodium iodide yielded monosodium salts, whereas treatment
      with bromotrimethylsilane cleaved both methyl groups while leaving the long-chain
      alkyl group intact. Neutralization of the resulting
      [(alkyloxy)carbonyl]phosphonic acids with 2 equiv of sodium methoxide afforded
      disodium salts of the phosphonic acid moiety. Similar chemistry was used to
      obtain the mono- and disodium salts of the cholesterol ester of PFA. Reaction of
      the triesters with phosphorous pentachloride, followed by coupling with AZT and O
      demethylation with sodium iodide, afforded 3'-azido-3'-deoxy-5'-O-[[(1
      octadecyloxy)carbonyl]phosphinyl ]thymidine (9a), 3'-azido-3'-deoxy-5'-O-[[(1
      eicosanyloxy)carbonyl]phosphinyl ]thymidine (9b), 3'-azido-3'-deoxy-5'-O-[[(1
      docosanyloxy)carbonyl]phosphinyl ]thymidine (9c), and 3'-azido-3'-deoxy-5'-O-[[(3
      beta-cholest-5-enyloxy)carbonyl]phosphinyl]thymidine (9d). Concentrations of 9a-d
      found to inhibit replication of wild-type HIV-1LAI by 50% (EC50 values) as
      measured in a plaque reduction assay were in the 0.1-0.3 microM range as compared
      with 0.013 microM for AZT and 133 microM for PFA. The concentration at which
      toxicity was observed in 50% of the host cells (TC50 values) as measured by a
      visual grading scale of cellular morphology was 10 microM for 9a and 9d, 32
      microM for 9b, and 320 microM for 9c. Thus, the TC50/EC50 ratio or selectivity
      index (SI) was 100 for 9a, 230 for 9b, and 1000 for 9c but only 33 for 9d,
      suggesting that the straight-chained fatty alcohol esters were more
      therapeutically selective. Similar TC50 and SI values were obtained for rapidly
      dividing CEM lymphoblasts as for HT4-6C cells. In assays against E89K, 9a-c had
      mean EC50 values of 0.13, 0.009, and 0.17 microM, whereas the EC50 of PFA was >
      1000 microM and that of AZT was 0.009 microM; thus, E89K was highly resistant to
      PFA but not cross-resistant to either AZT or the lipophilic PFA-AZT conjugates.
      In viral replication assays against the A018C-post isolate, the mean EC50 values
      of 9a-c were 0.30, 0.53, and 0.77 microM as compared with 2.9 microM for AZT and
      65 microM for PFA; thus, the virus recovered from a patient pretreated with AZT
      was not cross-resistant to either PFA or 9a-c. A notable feature of these results
      was that, in addition to being > 1000-fold more potent than PFA against the PFA
      resistant mutant, the lipophilic PFA-AZT conjugates were more potent than PFA, as
      well as AZT, against AZT-resistant HIV-1.

PMID- 9258356
TI  - 5-(Piperidin-2-yl)- and 5-(homopiperidin-2-yl)-1,4-benzodiazepines: high
      affinity, basic ligands for the cholecystokinin-B receptor.
AB  - The design, synthesis, and biological activity of a series of high-affinity,
      basic ligands for the cholecystokinin-B receptor are described. The compounds,
      which incorporate a piperidin-2-yl or a homopiperidin-2-yl group attached to C5
      of a benzodiazepine core structure, are substantially more basic (e.g., 9d, pKa =
      9.48) than previously reported antagonists based on 5-amino-1,4-benzodiazepines
      (e.g., 5, pKa = 7.1) and have improved aqueous solubility. In view of their
      basicity, it would be tempting to speculate that the present series of compounds
      might be binding to the CCK-B receptor in their protonated form. Compounds such
      as 9d, e and 10d showed high affinity for this receptor (IC50 < 2.5 nM) and very
      good selectivity over CCK-A (CCK-A/CCK-B > 2000), even as the racemates.
      Additionally, a significantly improved in vivo half-life was observed for a
      selection of compounds compared to the clinical candidate L-365, -260 (1).

PMID- 9258357
TI  - Protein structure-based design, synthesis, and biological evaluation of 5-thia
      2,6-diamino-4(3H)-oxopyrimidines: potent inhibitors of glycinamide ribonucleotide
      transformylase with potent cell growth inhibition.
AB  - The design, synthesis, biochemical, and biological evaluation of a novel series
      of 5-thia-2,6-diamino-4(3H)-oxopyrimidine inhibitors of glycinamide
      ribonucleotide transformylase (GART) are described. The compounds were designed
      using the X-ray crystal structure of human GART. The monocyclic 5
      thiapyrimidinones were synthesized by coupling an alkyl thiol with 5-bromo-2, 6
      diamino-4(3H)-pyrimidinone, 20. The bicyclic compounds were prepared in both
      racemic and diastereomerically pure forms using two distinct synthetic routes.
      The compounds were found to have human GART KiS ranging from 30 microM to 2 nM.
      The compounds inhibited the growth of both L1210 and CCRF-CEM cells in culture
      with potencies down to the low nanomolar range and were found to be selective for
      the de novo purine biosynthesis pathway. The most potent inhibitors had 2,5
      disubstituted thiophene rings attached to the glutamate moiety. Placement of a
      methyl substituent at the 4-position of the thiophene ring to give compounds 10,
      18, and 19 resulted in inhibitors with significantly decreased mFBP affinity.

PMID- 9258358
TI  - Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin
      inhibitor that blocks cartilage degradation in rabbits.
AB  - Structure-activity relationships of a lead hydroxamic acid inhibitor of
      recombinant human stromelysin were systematically defined by taking advantage of
      a concise synthesis that allowed diverse functionality to be explored at each
      position in a template. An ex vivo rat model and an in vivo rabbit model of
      stromelysin-induced cartilage degradation were used to further optimize these
      analogs for oral activity and duration of action. The culmination of these
      modifications resulted in CGS 27023A, a potent, orally active stromelysin
      inhibitor that blocks the erosion of cartilage matrix.

PMID- 9258359
TI  - Synthesis of nonhydrolyzable analogues of thiazole-4-carboxamide and benzamide
      adenine dinucleotide containing fluorine atom at the C2' of adenine nucleoside:
      induction of K562 differentiation and inosine monophosphate dehydrogenase
      inhibitory activity.
AB  - Thiazole-4-carboxamide adenine dinucleotide (TAD) analogue 7 containing a
      fluorine atom at the C2' arabino configuration of the adenine nucleoside moiety
      was found to be a potent inducer of differentiation of K562 erythroid leukemia
      cells. This finding prompted us to synthesize its hydrolysis-resistant
      methylenebis(phosphonate) and difluoromethylenebis(phosphonate) analogues 8 and
      9, respectively. Since both TAD and benzamide adenine dinucleotide (BAD) are
      potent inhibitors of inosine monophosphate dehydrogenase (IMPDH), the
      corresponding fluorine-substituted methylenebis(phosphonate) analogue 12 of BAD
      was also synthesized. Thus, 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine
      (13) was converted in five steps into the corresponding methylenebis(phosphonate)
      analogue 18. Dehydration of 18 with DCC led to the formation of the bicyclic
      trisanhydride intermediate 19a, which upon reaction with 2',3'-O
      isopropylidenetiazofurin (20) or -benzamide riboside (21) followed by hydrolysis
      and deprotection afforded the desired methylene-bridged dinucleotides 8 and 12,
      respectively. The similar displacement of the 5'-mesyl function of 2',3'-O
      isopropylidene-5'-O-mesyltiazofurin (24) with the difluoromethylenebis(phosphonic
      acid) derivative gave the phosphonate 25 which was coupled with 13 to afford 26.
      The desired difluoromethylenebis(phosphonate) analogue 9 was obtained by
      deprotection with Dowex 50/H+. This compound as well as beta-CF2-TAD (4) showed
      improved differentiation-inducing activity over beta-CH2-TAD (3), whereas
      analogues containing the -CH2-linkage (8 and 12) were inactive.

PMID- 9258360
TI  - Novel 99mTc aminobisthiolato/monothiolato "3 + 1" mixed ligand complexes:
      structure-activity relationships and preliminary in vivo validation as brain
      blood flow imaging agents.
AB  - A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general
      formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X
      CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been
      synthesized and evaluated in rodents for potential use in brain blood flow
      imaging. The complexes were prepared by ligand exchange reaction using 99mTc(V)O
      glucoheptonate as precursor and equimolar quantities of the two ligands. In all
      cases the syn isomer was formed in a high yield, whereas the anti isomer was not
      always present. The formation of two isomeric complexes-syn and anti-was
      expected, since the N-substituent (X-CH2CH2N) can assume syn or anti
      configuration with respect to the 99mTcO3+ core during complexation. One anti and
      all syn isomers were isolated by HPLC. Their identity was confirmed by
      comparative HPLC studies with the analogous 99Tc complexes of established
      structure. In vivo distribution, in particular brain uptake and retention,
      greatly depended on the type of either tridentate (L1H2) or monodentate (L2H)
      ligand. All 99mTc complexes showed significant brain uptake in mice (0.78-4.35%
      injected dose per organ at 5 min postinjection). This initial uptake remained
      nearly constant for at least 30 min for most of the complexes. Structure-activity
      relationships of novel 99mTc(V)O SNS/S complexes in mice are reported and
      discussed. Selected complexes were further studied in rats. High brain uptake,
      comparable to that of 99mTc-d,l-HMPAO, and sufficient retention 60 min
      postinjection were provided with complex 18 [X = (C2H5)2N and R = p-CH3OC6H4CH2].

PMID- 9258361
TI  - Steroidal glycoside cholesterol absorption inhibitors.
AB  - We have explored the use of steroidal glycosides as cholesterol absorption
      inhibitors which act through an unknown mechanism. The lead for this program was
      tigogenin cellobioside (1, tiqueside) which is a weak inhibitor (ED50 = 60 mg/kg)
      as measured in an acute hamster cholesterol absorption assay. Modification of the
      steroid portion of the molecule led to the discovery of 11-ketotigogenin
      cellobioside (5, pamaqueside) which has an ED50 of 2 mg/kg. Replacement of the
      cellobiose with other sugars failed to provide more potent analogs. However,
      large improvements in potency were realized through modification of the hydroxyl
      groups on the cellobiose. This strategy ultimately led to the 4", 6"-bis[(2
      fluorophenyl)carbamoyl]-beta-D-cellobiosyl derivative of 11-ketotigogenin (51)
      with an ED50 of 0.025 mg/kg in the hamster assay, as well as the corresponding
      hecogenin analog 64 (ED50 = 0.07 mg/kg).

PMID- 9258362
TI  - The role of phenylalanine at position 6 in glucagon's mechanism of biological
      action: multiple replacement analogues of glucagon.
AB  - Extensive evidence gathered from structure-activity relationship analysis has
      identified and confirmed specific positions in the glucagon sequence that are
      important either for binding to its receptor or for signal transduction. Fifteen
      glucagon analogues have been designed and synthesized by incorporating structural
      changes in the N-terminal region of glucagon, in particular histidine-1,
      phenylalanine-6, and aspartic acid-9. This investigation was conducted to study
      the role of phenylalanine at position 6 on the glucagon mechanism of action.
      These glucagon analogues have been made by either deleting or substituting
      hydrophobic groups, hydrophilic groups, aromatic amino acids, or a D
      phenylalanine residue at this position. The structures of the new analogues are
      as follows: [des-His1, des-Phe6, Glu9]glucagon-NH2 (1); [des
      His1,Ala6,Glu9]glucagon-NH2 (2); [des-His1,Tyr6,Glu9]glucagon-NH2 (3); [des
      His1,Trp6,Glu9]-glucagon-NH2 (4); [des-His1,D-Phe6,Glu9]glucagon-NH2 (5); [des
      His1,Nle6,Glu9]glucagon-NH2 (6); [des-His1,Asp6,Glu9]glucagon-NH2 (7); [des
      His1,des-Gly4,Glu9]glucagon-NH2 (8); [desPhe6,-Glu9]glucagon-NH2 (9); [des
      Phe6]glucagon-NH2 (10); [des-His1, des-Phe6]glucagon-NH2 (11); [des-His1, des
      Phe6,Glu9]glucagon (12); [des-Phe6,Glu9]glucagon (13); [des-Phe6]glucagon (14);
      and [des-His1, des-Phe6]glucagon (15). The receptor binding potencies IC50 values
      are 48 (1), 126 (2), 40 (3), 19 (4), 100 (5), 48 (6), 2000 (7), 52 (8), 113 (9),
      512 (10), 128 (11), 1000 (12), 2000 (13), 500 (14), and 200 nM (15). All
      analogues were found to be antagonists unable to activate the adenylate cyclase
      system even at concentrations as high as 10(-5) M except for analogues 6 and 8,
      which were found to be weak partial agonists/partial antagonists with maximum
      stimulation between 6-12%. In competitive inhibition experiments, all the
      analogues caused a right shift of the glucagon-stimulated adenylate cyclase dose
      response curve. The pA2 values were 8.20 (1), 6.40 (2), 6.20 (3), 6.25 (4), 6.30
      (5), 6.30 (7), 6.05 (8), 6.20 (9), 6.30 (10), 6.25 (11), 6.10 (12), 6.20 (13),
      6.20 (14), and 6.35 (15).

PMID- 9258363
TI  - The chemistry of pseudomonic acid. 18. Heterocyclic replacement of the alpha,beta
      unsaturated ester: synthesis, molecular modeling, and antibacterial activity.
AB  - The electronic requirements around the C1-C3 region of pseudomonic acid analogues
      were investigated. Synthetic routes were developed to access a range of compounds
      where the alpha, beta-unsaturated ester moiety had been replaced by a 5-membered
      ring heterocycle. The inhibition of isoleucyl tRNA synthetase from Staphylococcus
      aureus NCTC 6571 was determined as was the minimum inhibitory concentration (MIC)
      of the test compounds against that organism. Compounds possessing a region of
      electrostatic potential corresponding to that of the carbonyl group in the alpha,
      beta-unsaturated ester, and a low-energy unoccupied molecular orbital in the
      region corresponding to the double bond, were found to have IC50 values of 0.7
      5.3 ng mL-1. However the MIC values of these compounds were in the range 2.0-8.0
      micrograms mL-1, reflecting their poorer penetration into the bacterial cell.

PMID- 9258364
TI  - H3-receptor antagonists: synthesis and structure-activity relationships of para-
      and meta-substituted 4(5)-phenyl-2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazoles.
AB  - We report the synthesis, octanol/water partition coefficient (log P),
      dissociation constants (pKa), H3-receptor affinity (pKi in rat brain membranes,
      [3H]-N alpha-methylhistamine), and H3-antagonist potency (pA2 in guinea ileum,
      (R)-alpha-methylhistamine) of novel H3-receptor antagonists obtained by
      introducing a para or meta substituent on the phenyl ring of the lead compound
      4(5)-phenyl-2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazole (3a). The substituents
      were chosen to obtain broad and uncorrelated variation in their lipophilic,
      electronic, and steric properties. The log P values of the neutral species cover
      almost 3 orders of magnitude (from 1.40 to 4.11). The pKa,2 values (protonation
      of the 2-thioimidazole fragment) vary from 3.13 to 4.34, indicating that this
      fragment, which incorporates the so-called polar group common to many H3-receptor
      antagonists, is neutral at physiological pH. The compounds had pKi values in a
      range too narrow (from 7.28 to 8.03) to derive QSAR equations. In one case (3g),
      a biphasic displacement curve was observed (pKi,1 = 8.53; pKi,2 = 6.90). The pA2
      values ranged 2 orders of magnitude (from 6.83 to 8.87) and yielded a QSAR model
      (PLS) indicating that antagonist potency depends parabolically on lipophilicity
      and is decreased by bulky para substituents. The compounds of this series,
      therefore, maintain a fair-to-good affinity for rat brain H3-receptor and a fair
      to-good H3-antagonist potency on guinea pig ileum, although varying markedly in
      their lipophilicity. The series thus appears as a good candidate for
      pharmacokinetic optimization leading to brain-penetrating H3-receptor
      antagonists.

PMID- 9258365
TI  - Helix-inducing alpha-aminoisobutyric acid in opioid mimetic deltorphin C
      analogues.
AB  - The achiral symmetric alpha-aminoisobutyric acid (Aib) replaced the critical N
      terminal residues of the amphibian skin opioid deltorphin C (H-Tyr-D-Ala-Phe-Asp
      Val-Val-Gly-NH2) without detriment to the physicochemical requirements for delta
      opioid receptor recognition. Substitutions by the alpha, alpha-dialkyl amino acid
      in place of D-Ala2 or Phe3, or both, exhibited high delta receptor affinity (Ki
      delta = 0.12-3.6 nM) and 5-9-fold greater selectivity (Ki mu/Ki delta = 5000
      8500) than the parent compound. This is the first definitive demonstration that
      the D-chirality of alanine and the aromaticity of phenylalanine are replaceable
      by an achiral alpha, alpha-dialkylated residue without detrimental effects on
      ligand binding. Incorporation of the mono-alpha-alkyl amino acid L- or D-Ala at
      the third position also produced highly selective delta ligands (Ki mu/Ki delta =
      2000-3500), albeit with reduced delta affinities (Ki delta = 6-15 nM).
      Replacement of the anionic residue Asp4 by Aib yielded an opioid peptide that fit
      two-site binding models for the delta receptor (eta = 0.763; P < 0.0001) and
      displayed dual high affinity for both delta and mu receptors, emphasizing the
      repulsive effect by a negative charge at mu receptor sites and the insignificance
      of Asp for delta affinity. Molecular dynamics conformation analyses suggested
      that Aib residues caused distinct changes in deltorphin C secondary structure
      when substituted for D-Ala2, Asp4, and simultaneously D-Ala2 and Phe3 but not
      when substituted for Phe3. These conformational changes might be critical factors
      for the proper orientation of reactive constituents of residues in the N-terminal
      region of deltorphin C. Disparities between binding data and functional bioassays
      of [Aib3] indicated that Phe3 was required for bioactivity in mouse vas deferens
      but not for interaction with delta opioid receptors in rat brain membranes.

PMID- 9258366
TI  - Mutagenesis reveals structure-activity parallels between human A2A adenosine
      receptors and biogenic amine G protein-coupled receptors.
AB  - Structure-affinity relationships for ligand binding at the human A2A adenosine
      receptor have been probed using site-directed mutagenesis in the transmembrane
      helical domains (TMs). The mutant receptors were expressed in COS-7 cells and
      characterized by binding of the radioligands [3H]CGS21680, [3H]NECA, and [3H]XAC.
      Three residues, at positions essential for ligand binding in other G protein
      coupled receptors, were individually mutated. The residue V(3.32) in the A2A
      receptor that is homologous to the essential aspartate residue of TM3 in the
      biogenic amine receptors, i.e., V84(3.32), may be substituted with L (present in
      the A3 receptor) but not with D (in biogenic amine receptors) or A. H250(6.52),
      homologous to the critical N507 of rat m3 muscarinic acetylcholine receptors, may
      be substituted with other aromatic residues or with N but not with A (Kim et al.
      J. Biol. Chem. 1995, 270, 13987-13997). H278(7.43), homologous to the covalent
      ligand anchor site in rhodopsin, may not be substituted with either A, K, or N.
      Both V84L(3.32) and H250N(6.52) mutant receptors were highly variable in their
      effect on ligand competition depending on the structural class of the ligand.
      Adenosine-5'-uronamide derivatives were more potent at the H250N(6.52) mutant
      receptor than at wild type receptors. Xanthines tended to be close in potency
      (H250N(6.52)) or less potent (V84L(3.32)) than at wild type receptors. The
      affinity of CGS21680 increased as the pH was lowered to 5.5 in both the wild type
      and H250N(6.52) mutant receptors. Thus, protonation of H250(6.52) is not involved
      in this pH dependence. These data are consistent with a molecular model
      predicting the proximity of bound agonist ligands to TM3, TM5, TM6, and TM7.

PMID- 9258367
TI  - Structure-activity relationships of 4-(phenylethynyl)-6-phenyl-1,4
      dihydropyridines as highly selective A3 adenosine receptor antagonists.
AB  - 4-(Phenylethynyl)-6-phenyl-1,4-dihydropyridine derivatives are selective
      antagonists at human A3 adenosine receptors, with Ki values in a radioligand
      binding assay vs [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-(N
      methylcarbamoyl)adenosine) in the submicromolar range. In this study, structure
      activity relationships at various positions of the dihydropyridine ring (the 3-
      and 5-acyl substituents, the 4-aryl substituent, and 1-methyl group) were probed
      synthetically. Using the combined protection of the 1-ethoxymethyl and the 5-[2
      (trimethylsilyl)ethyl] ester groups, a free carboxylic acid was formed at the 5
      position allowing various substitutions. Selectivity of the new analogues for
      cloned human A3 adenosine receptors was determined vs radioligand binding at rat
      brain A1 and A2A receptors. Structure-activity analysis at adenosine receptors
      indicated that pyridyl, furyl, benzofuryl, and thienyl groups at the 4-position
      resulted in, at most, only moderate selectivity for A3 adenosine receptors. Ring
      substitution (e.g., 4-nitro) of the 4-phenylethylnyl group did not provide
      enhanced selectivity, as it did for the 4-styryl-substituted dihydropyridines. At
      the 3-position of the dihydropyridine ring, esters were much more selective for
      A3 receptors than closely related thioester, amide, and ketone derivatives. A
      cyclic 3-keto derivative was 5-fold more potent at A3 receptors than a related
      open-ring analogue. At the 5-position, a homologous series of phenylalkyl esters
      and a series of substituted benzyl esters were prepared and tested.
      (Trifluoromethyl)-, nitro-, and other benzyl esters substituted with electron
      withdrawing groups were specific for A3 receptors with nanomolar Ki values and
      selectivity as high as 37000-fold. A functionalized congener bearing an
      [(aminoethyl)amino]carbonyl group was also prepared as an intermediate in the
      synthesis of biologically active conjugates.

PMID- 9258368
TI  - Design and synthesis of novel imidazole-substituted dipeptide amides as potent
      and selective inhibitors of Candida albicans myristoylCoA:protein N
      myristoyltransferase and identification of related tripeptide inhibitors with
      mechanism-based antifungal activity.
AB  - A new class of antifungal agents has been discovered which exert their activity
      by blockade of myristoylCoA: protein N-myristoyltransferase (NMT; EC 2.1.3.97).
      Genetic experiments have established that NMT is needed to maintain the viability
      of Candida albicans and Cryptococcus neoformans,the two principal causes of
      systemic fungal infections in immunocompromised humans. Beginning with a weak
      octapeptide inhibitor ALYASKLS-NH2 (2, Ki = 15.3 +/- 6.4 microM), a series of
      imidazole-substituted Ser-Lys dipeptide amides have been designed and synthesized
      as potent and selective inhibitors of Candida albicans NMT. The strategy that led
      to these inhibitors evolved from the identification of those functional groups in
      the high-affinity octapeptide substrate GLYASKLS-NH2 1a necessary for tight
      binding, truncation of the C-terminus, replacement of the four amino acids at the
      N-terminus by a spacer group, and substitution of the glycine amino group with an
      N-linked 2-methylimidazole moiety. Initial structure-activity studies led to the
      identification of 31 as a potent and selective peptidomimetic inhibitor with an
      IC50 of 56 nM and 250-fold selectivity versus human NMT. 2-Methylimidazole as the
      N-terminal amine replacement in combination with a 4-substituted phenacetyl
      moiety imparts remarkable potency and selectivity to this novel class of
      inhibitors. The (S,S) stereochemistry of serine and lysine residues is critical
      for the inhibitory activity, since the (R,R) enantiomer 40 is 10(3)-fold less
      active than the (S,S) isomer 31. The inhibitory profile exhibited by this new
      class of NMT ligands is a function of the pKa of the imidazole substituent as
      illustrated by the benzimidazole analog 35 which is about 10-fold less potent
      than 31. The measured pKa (7.1 +/- 0.5) of 2-methylimidazole in 31 is comparable
      with the estimated pKa (approximately 8.0) of the glycyl residue in the high
      affinity substrate 1a. Groups bulkier than methyl, such as ethyl, isopropyl, or
      iodo, at the imidazole 2-position have a detrimental effect on potency. Further
      refinement of 31 by grafting an alpha-methyl group at the benzylic position
      adjacent to the serine residue led to 61 with an IC50 of 40 nM. Subsequent chiral
      chromatography of 61 culminated in the discovery of the most potent Candida NMT
      inhibitor 61a reported to date with an IC50 of 20 nM and 400-fold selectivity
      versus the human enzyme. Both 31 and 61a are competitive inhibitors of Candida
      NMT with respect to the octapeptide substrate GNAASARR-NH2 with Ki(app) = 30 and
      27 nM, respectively. The potency and selectivity displayed by these inhibitors
      are dependent upon the size and orientation of the alpha-substituent. An alpha
      methyl group with the R configuration corresponding to the (S)-methyl-4-alanine
      in 2 confers maximum potency and selectivity. Structural modification of 31 and
      61 by appending an (S)-carboxyl group beta to the cyclohexyl moiety provided the
      less potent tripeptide inhibitors 73a and 73b with an IC50 of 1.45 +/- 0.08 and
      0.38 +/- 0.03 microM, respectively. However, these tripeptides (73a and 73b)
      exhibited a pronounced selectivity of 560- and 2200-fold versus the human NMT.
      More importantly 73a displayed fungistatic activity against C albicans with an
      EC50 of 51 +/- 17 microM in cell culture. Compound 73b also exhibited a similar
      antifungal activity. An Arf protein gel mobility shift assay for monitoring
      intracellular myristoylation revealed that a single dose of 200 microM of 73a or
      73b produced < 50% reduction in Arf N-myristoylation, after 24 and 48 h,
      consistent with their fungistatic rather than fungicidal activity. In contrast,
      the enantiomer 73d which had an IC50 > 1000 microM against C. albicans NMT did
      not exhibit antifungal activity and produced no detectable reduction in Arf N
      myristoylation in cultures of C. albicans. These studies confirm that the
      observed antifungal activity of 73a and 73b is due to the attenuation of NMT
      activity and that NMT represents an attractive tar

PMID- 9258369
TI  - Synthesis and antimetastatic activity of L-iduronic acid-type 1-N-iminosugars.
AB  - L-Iduronic acid-type 1-N-iminosugars, (3R,4S,5R,6R)- and (3R,4S,5S,6R)-6
      acetamido-4-amino-5-hydroxypiperidine-3-carboxylic acid (6 and 7, respectively),
      (3R,4S,5R,6R)-6-acetamido-4- guanidino-5-hydroxypiperidine-3-carboxylic acid (8),
      and (3R,4S,5R,6R)-4-amino- and -guanidino-5-hydroxy-6-(trifluoroacetamido)
      piperidine-3-carboxylic acid (9 and 10, respectively), were synthesized from
      siastatin B (1), isolated from Streptomyces culture, by the intramolecular
      Michael addition of O-imidate to its alpha,beta-unsaturated ester through cis
      oxiamination as a key step. Preincubation of B16 BL6 cells with these compounds
      inhibited invasion of the cells through reconstituted basement membranes.
      Pulmonary metastasis of B16 BL6 cells in mice was remarkably inhibited by
      pretreatment of the cells with these compounds in culture.

PMID- 9258370
TI  - Structure-activity relationships for the antileishmanial and antitrypanosomal
      activities of 1'-substituted 9-anilinoacridines.
AB  - Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing
      lipophilic electron-donating 1'-anilino substituents are active against both the
      promastigote and amastigote forms of the parasite Leishmania major. A series of
      analogues of the known 1'-NHhexyl lead compound were prepared and evaluated
      against L. major in macrophage culture to further develop structure-activity
      relationships (SAR). Toxicity toward mammalian cells was measured in a human
      leukemia cell line, and the ratio of the two IC50 values (IC50(J)/IC50(L)) was
      used as a measure of the in vitro therapeutic index (IVTI). A 3,6-diNMe2
      substitution pattern on the acridine greatly increased toxicity to L. major
      without altering mammalian toxicity, increasing IVTIs over that of the lead
      compound. The 2-OMe, 6-Cl acridine substitution pattern used in the antimalarial
      drug mepacrine also resulted in potent antileishmanial activity and high IVTIs.
      Earlier suggestions of the utility of 2'-OR groups in lowering mammalian
      cytotoxicity were not borne out in this wider study. A series of very lipophilic
      1'-NRR (symmetric dialkylamino)-substituted analogues showed relatively high
      antileishmanial potency, but no clear trend was apparent across the series, and
      none were superior to the 1'-NH(CH2)5Me subclass. Subsets of the most active 1'
      N(R)(CH2)5Me- and 1'-N(alkyl)2-substituted compounds against L. major were also
      evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei,
      but no consistent SAR could be discerned in these physiologically diverse test
      systems. The present study has confirmed earlier conclusions that lipophilic
      electron-donating groups at the 1'-position of 9-anilinoacridines provide high
      activity against L. major, but the SAR patterns observed do not carry over to the
      other parasites studied.

PMID- 9258372
TI  - Synthesis and structure-activity relationships of a new model of arylpiperazines.
      3.1 2-[omega-(4-arylpiperazin-1-yl)alkyl]perhydropyrrolo- [1,2-c]imidazoles and 
      perhydroimidazo[1,5-a]pyridines: study of the influence of the terminal amide
      fragment on 5-HT1A affinity/selectivity.
AB  - A series of new arylpiperazine derivatives 2, which are devoid of the terminal
      amide fragment present in related 5-HT1A ligands, was prepared and evaluated for
      affinity at 5-HT1A and alpha 1 receptors. All the compounds 2 demonstrated high
      affinity for the 5-HT1A receptor and moderate affinity for alpha 1 receptor
      binding sites. Structure-activity relationship (SAR) studies suggest that there
      is influence of electronic factors on the no-pharmacophoric part of the alpha 1
      receptor site. However there is no influence of electronic interactions on the
      stabilization of the 5-HT1A receptor-ligand complex.

PMID- 9258371
TI  - A novel radioiodination reagent for protein radiopharmaceuticals with L-lysine as
      a plasma-stable metabolizable linkage to liberate m-iodohippuric acid after
      lysosomal proteolysis.
AB  - Radiochemical design of polypeptides using metabolizable linkages would be
      attractive to enhance target-selective localization of radioactivity for
      diagnostic and therapeutic nuclear medicine. However, while use of ester bonds as
      the linkage allows selective release of the designed radiometabolite from
      covalently conjugated polypeptides after lysosomal proteolysis in nontarget
      tissues, low plasma stability of ester bonds causes a decrease in radioactivity
      levels of the target. In pursuit of new metabolizable linkages that provide
      stable attachment of radiolabels with polypeptide in plasma while facilitating
      rapid and selective release of designed radiometabolites of rapid urinary
      excretion in lysosomes, a new radioiodination reagent with L-lysine as the
      metabolizable linkage to liberate m-iodohippuric acid (L-HML) was designed and
      synthesized. Stabilities of the metabolizable linkage in serum and cleavabilities
      of the linkage in lysosomal proteolysis in hepatic cells were investigated after
      conjugation of [131I]-L-HML with galactosyl-neoglycoalbumin (NGA). For
      comparison, a radioiodination reagent with an ester bond to release m
      iodohippuric acid (MIH) was conjugated with NGA under similar conditions. When
      incubated in human serum, [131I]-L-HML-NGA liberated less than 3% of the initial
      radioactivity after 24 h, whereas [125I]MIH-NGA released more than 60% of its
      radioactivity during the same interval. In biodistribution studies, [131I]-L-HML
      NGA demonstrated radioactivity elimination from murine liver at a rate and
      excretion route similar to [125I]MIH-NGA. Analyses of murine urine after
      injection of [131I]-L-HML-NGA indicated a single radioactivity peak at fractions
      identical to those of m-iodohippuric acid. Biodistribution studies of
      radioiodinated NGAs with D-lysine or cadaverine as the linkages demonstrated a
      delayed elimination rate from murine liver with significantly higher
      radioactivity being excreted in the feces at 24 h postinjection. Thus, L-HML is
      the first reagent that allows stable attachment of radiolabel with polypeptide in
      serum while facilitating selective release of a radiometabolite with rapid
      urinary excretion from covalently conjugated polypeptides after lysosomal
      proteolysis at a rate similar to that of ester bonds. Thus, L-HML is potentially
      useful for the radioiodination of polypeptides for diagnostic and therapeutic
      purposes.

PMID- 9258373
TI  - Measuring health care quality: methodological challenges.

PMID- 9258374
TI  - Methodological challenges in measurements of functional ability in gerontological
      research. A review.
AB  - This article addresses two important challenges in the measurement of functional
      ability in gerontological research: the first challenge is to connect
      measurements to a theoretical frame of reference which enhances our understanding
      and interpretation of the collected data; the second relates to validity in all
      stages of the research from operationalization to meaningful follow-up
      measurements in longitudinal studies. Advantages and disadvantages in different
      methods to do the measurements of functional ability are described with main
      focus on frame of reference, operationalization, practical procedure, validity,
      discriminatory power, and responsiveness. In measures of functional ability it is
      recommended: 1) always to consider the theoretical frame of reference as part of
      the validation process (e.g., the theory of "The Disablement Process"; 2) always
      to assess whether the included activities and categories are meaningful to all
      people in the study population before they are combined into an index and before
      tests for construct validity; 3) not to combine mobility, PADL and IADL in the
      same index/scale; 4) not to use IADL as a health-related functional ability
      measure or, if used, to ask whether problems with IADL or non-performance of IADL
      are caused by health-related factors; 5) always to make analyses of functional
      ability for men and women separately as patterns of functional ability and
      patterns of associations between other variables and functional ability often
      vary for men and women; and 6) to exclude the dead in analyses of change in
      functional ability if the focus is on predictors of deterioration in functional
      ability.

PMID- 9258375
TI  - Formal education as an effect modifier of the relationship between Mini-Mental
      State Examination score and IADLs disability in the older population.
AB  - The objective of this retrospective, case-series study was to examine the
      relationship between disability in Instrumental Activities of Daily Living
      (IADLs) and cognitive impairment measured by the Mini-Mental State Examination
      (MMSE), and how this relationship was influenced by different levels of formal
      education. The setting of the study was the Cognitive Disorders Center of the
      Local Sanitary Unit (USL) No. 4 in Prato (Italy). Independence in IADL was
      strongly related to MMSE scores. A score of less than 24 at the MMSE was
      predictive of disability in at least one IADL with 0.82 sensitivity and 0.73
      specificity. However, when only people with a very low level of formal education
      were considered, the best threshold predicting IADL disability was 17
      (sensitivity 0.76, specificity 0.75). Thus, scholastic achievement is an effect
      modifier of the relationship between cognitive status, as measured by the MMSE,
      and IADL disability. Subjects with low education level and poor performance at
      the MMSE are often independent in activities making demand on cognitive function,
      such as IADLs. These results suggest that a lower MMSE cut-off score should be
      considered when screening for cognitive impairment in these persons.

PMID- 9258376
TI  - Postoperative delirium easily develops in patients with intramitochondrial
      inclusion bodies in colonic neurons.
AB  - Patients whose colons were resected for carcinoma were studied in order to
      determine the relationship between clinical findings-which included development
      of postoperative delirium- and intramitochondrial inclusion bodies (MI) in the
      neurons in the colon. Twenty-three patients had MI and 24 patients did not.
      Preoperative dementia was present in 9 (39.1%) of the 23 patients with MI, and in
      7 (29.2%) of the 24 without it. Postoperative delirium developed in 13 (56.3%) of
      the 23 with MI, and in 5 (20.8%) of the 24 without it (p < 0.05). Excluding
      preoperative dementia, postoperative delirium developed in 5 (35.7%) of the 14
      with MI, and in none of the 17 without it. Changes in the neurons in the colon
      were not related to dementia. The changes may have been related to the functions
      of the central nervous system, because patients with MI were likely to develop
      postoperative delirium.

PMID- 9258377
TI  - Function of GH/IGF-I axis in aging: multicenter study in 152 healthy elderly
      subjects with different degrees of physical activity. Italian Association for
      Research on Brain Aging (AIRIC) Multicenter Study Group.

PMID- 9258378
TI  - Effects of six-month administration of recombinant human growth hormone to
      healthy elderly subjects.
AB  - In aging, both changes in body composition and a decrease in GH secretion are
      observed. While recombinant human GH (rhGH) therapy was shown to be effective in
      GH-deficient adults, its effects on normal aging are controversial. This study
      addressed the effects of six-month administration of low dosages of rhGH in a
      group of 5 healthy elderly subjects (age range 71-86 years). All subjects
      received 2 IU rhGH (Saizen, Serono) x 2/week s.c., which was approximately 0.03
      mg/kg/week, and were examined before and 1, 3, and 6 months after the start of
      the therapy, as well as 3 months after therapy was suspended. Hormonal, metabolic
      and biochemical parameters, as well as bone density at the forearm level, body
      composition and muscle strength, assessed by isokinetic exercises, were evaluated
      at each scheduled visit. After the start of the therapy, there was an average 9
      +/- 3% increase (median 8%) in IGF-I levels (IGF-I basal: 145.6 +/- 9 ng/mL, IGF
      I peak: 176.0 +/- 10; p < 0.001). An increase in lean body weight, a decrease in
      fat (p < 0.05), and an improvement in muscle strength (p < 0.01) were recorded.
      No significant variation was observed in the metabolic parameters. During rhGH
      therapy, an increase in both bone resorption and formation parameters, and a
      slightly decreasing trend in bone density were noted. In conclusion, low dosages
      of rhGH in healthy elderly subjects seem to determine some physiological effects,
      such as a slight increase in IGF-I levels, which in turn may be responsible for
      the positive effects on body mass composition and muscle strength, without
      producing side effects. On the other hand, 6-month subcutaneous rhGH therapy at
      the dosage employed was unable to improve bone density.

PMID- 9258379
TI  - Responses of circulating urea cycle and branched-chain amino acids to feeding in
      adult and aged Fischer-344 rats.
AB  - Amino acid concentrations in plasma and blood were compared between adult (6
      months) and aged (22 months) male rats in fed and food-deprived (fasted) states.
      Since feeding is known to elevate plasma amino acids, rats were sampled after
      food had been freely available to them and after food was withheld for 20 hours.
      Fourteen amino acids increased (8 to 74%) in blood and plasma in fed rats
      compared to food-deprived rats. Blood concentrations of four amino acids
      (cystine, aspartate, threonine, and phosphoserine) were increased in aged
      compared to adult rats, while tyrosine was 10% lower. The interaction between fed
      state and age was significant for the branched-chain amino acids (BCAA) as they
      increased 23% in the blood and plasma of fed compared to food-deprived adult
      rats; however, BCAA were not affected by feeding state in the aged rats. Plasma
      arginine concentration was 12% lower (p < 0.001) and citrulline was 20% higher (p
      < 0.005) in aged compared to adult rats, and consequently the citrulline:arginine
      ratio was elevated by 36% in aged rats. Our results demonstrate that, although
      the total arginine in whole blood is not altered or is increased with aging, less
      of the arginine is transported in the plasma of aged compared to adult rats.
      Furthermore, these results indicate altered metabolism of the urea cycle amino
      acids and BCAA with aging in the rat.

PMID- 9258380
TI  - Factors that disturb sleep in nursing home residents.
AB  - The purpose of this cross-sectional survey was to examine subjective sleep
      quality, and identify factors that disturb sleep in cognitively intact nursing
      home (NH) residents. We interviewed 51 cognitively intact NH residents using a
      validated instrument, the Pittsburgh Sleep Quality Index (PSQI). Questions
      regarding the environment, symptoms suggestive of restless leg syndrome, and
      periodic leg movements were also asked. Three individuals were unable to answer
      all the questions and, therefore, analyses were performed on 48 subjects. Seventy
      three percent of the subjects were identified as "poor" sleepers based upon a
      total PSQI score > 5. Factors that disturbed the residents' sleep three or more
      times a week were: nocturia (71%), environment-related noise or light (38%), pain
      (33%), feeling too hot (6%) and leg cramps (6%). On multiple regression analysis,
      poor sleep correlated with depressive symptoms and comorbidity, not with age or
      gender. Poor sleep quality is common among cognitively intact NH residents. In
      our study, nocturia, environmental factors and pain were the most commonly
      perceived causes of sleep disturbance. Poor sleep independently correlated with
      depressive symptoms and comorbidity. These findings should be kept in mind when
      evaluating sleep complaints in the nursing home.

PMID- 9258381
TI  - Characteristics of long-surviving men: results from a nine-year longitudinal
      study.
AB  - Although the life expectancy of men is commonly less than that of women, previous
      analyses of a longitudinal data set revealed a sub-sample of older men whose
      survival curves over twenty years are similar to those of the women in the
      sample. The main purpose of this research is to identify factors which
      differentiate this group of "successful" males from the other males in the
      sample. Data from the two groups of males (and two groups of females) were
      examined using analysis of variance, chi 2 analysis, and survival analysis. Data
      include measures in a variety of biomedical, functional, behavioral, and
      psychological areas collected during in-home and hospital examinations. Results
      show that "successful" males have significantly higher scores in both cognitive
      abilities and health, initially and at longitudinal follow-ups. The combination
      of overall high scores in the multiple domains evidently gives this group of men
      an advantage over the others. The results emphasize the importance of recognizing
      the sub-groups in the aging population with different developmental patterns, and
      tailoring both research and services to the uniqueness of these groups.

PMID- 9258382
TI  - Altered oxidative stress in healthy old subjects.
AB  - To understand the magnitude of oxidative phenomena during senescence, we
      evaluated, as antioxidant, the activity of glutathione peroxidase (GSH-Px) in
      erythrocytes and plasma uric acid (UA) levels together with the malondialdehyde
      (MDA) levels in plasma, as an index of lipid peroxidation, in 46 apparently
      healthy elderly subjects (87 +/- 6 years old; mean +/- SD), and 49 young subjects
      (29 +/- 4 years old). The elderly subjects had lower erythrocyte GSH-Px activity
      (15.7 +/- 4.8 vs 20.2 +/- 7.0 U/g Hb, p < 0.001; mean +/- SD) and plasma UA
      levels (192 +/- 46 vs 240 +/- 54 mmol/L, p < 0.001), but higher MDA levels (5.3
      +/- 0.8 vs 4.1 +/- 0.8 mmol/L, p < 0.001) than the young subjects. Of additional
      interest was the finding of a positive correlation between age and erythrocyte
      GSH-Px activity (r = 0.74, p < 0.001), and a negative correlation between age and
      plasma MDA levels (r = -0.83, p < 0.001) in the elderly group. Although
      erythrocyte (GSH-Px activity was significantly less in the elderly than in the
      young group, the oldest subjects showed the greatest erythrocyte GSH-Px activity
      and had lower MDA levels.

PMID- 9258383
TI  - Raising the level of medical gerontology: evaluation of the European Academy for
      Medicine of Ageing course. European Professors of Medical Gerontology.
AB  - The two-year EAMA course was established in 1995 by the Group of European
      Professors in Medical Gerontology (GEPMG) with the aim of raising the global
      standard of medical gerontology in (chiefly) European junior faculties. To
      determine the impact of this new course, a careful evaluation was made on each of
      its various goals. Thirty-five and thirty-eight students, selected by national
      professional societies from 15 different European countries, plus Israel and
      Mexico, took part in the first two one-week sessions. On the basis of daily and
      weekly evaluations, performed by both students themselves and teachers, we can
      say that the first two EAMA sessions succeeded in reaching their main goals:
      enhancing and updating knowledge, better identifying deficiencies, improving
      skills in gathering data, establishing priorities, expressing important messages,
      leading discussions, and creating an international network in medical
      gerontology. The next two EAMA sessions will hopefully confirm these conclusions.

PMID- 9258384
TI  - Work-related asthma and respiratory symptoms among workers exposed to metal
      working fluids.
AB  - The objective of this work was to determine whether the prevalence of respiratory
      symptoms differed among workers exposed to different types of metal-working
      fluids. As part of a mandatory surveillance system for occupational illness, from
      1988-1994, the Michigan Department of Public Health received, 86 occupational
      disease reports of work-related asthma secondary to exposure to metal-working
      fluids. As part of a public health program, follow-up industrial hygiene
      inspections, including medical interviews of the workforce, were performed at
      companies where the reported cases had become ill. Metal-working fluids were the
      second most common cause of work-related asthma reported in the state. Most of
      the reports were from the automobile industry. Follow-up inspections were
      conducted at 37 facilities where the individuals with work-related asthma had
      worked. Seven hundred and fifty-five workers at these facilities were
      interviewed. Only one facility was above the allowable oil mist standard. Despite
      the exposure levels being within the legal limits, approximately 20% of the
      fellow workers of the reported cases had daily or weekly respiratory symptoms
      suggestive of work-related asthma. Workers exposed to emulsified, semisynthetic,
      or synthetic machining coolants were more likely to have chronic bronchitis; to
      have visited a doctor for shortness of breath; to have visited a doctor for a
      sinus problem; to be bothered at work by nasal stuffiness, runny nose, or sore
      throat; and to have an increased prevalence of respiratory symptoms consistent
      with work-related asthma, compared to workers exposed to mineral oil metal
      working fluids. These findings were found in individuals who currently smoked,
      had never smoked or were ex-cigarette smokers. Further research to determine the
      chemical components or microbial contaminants responsible for these findings is
      needed.

PMID- 9258385
TI  - Bronchoalveolar lavage findings in firefighters.
AB  - Firefighters are exposed to irritating, asphyxiating toxic gases and aerosols.
      Previous studies indicate that this may result in acute as well as chronic lung
      function impairment. It is well known that inhalation of organic material can
      cause alveolitis. The purpose of this study was to investigate whether
      firefighters repeatedly exposed to fire gases and other combustion products
      develop inflammatory changes in the lower airways and, if so, what subtype of
      cells and soluble components accumulate. Thirteen nonsmoking firefighters
      underwent bronchoalveolar lavage (BAL), and the results were compared to a
      reference group of 112 nonsmoking healthy volunteers. The firefighters showed
      lower recovery of instilled lavage fluid (61% vs 72%; P < 0.01) and an increase
      in the proportion of lymphocytes in that fluid (8.2% vs 5.7%; P < 0.05). Alveolar
      macrophage fluorescence, which is a sign of uptake of inhaled fluorescent
      material, rather than a reflection of the degree of inflammation, was increased
      in two firefighters. Further, the lavage fluid had higher concentrations of
      native fibronectin (34.6 vs 22.0 micrograms/L; P < 0.01) and hyaluronic acid
      (27.7 vs 10.0 micrograms/L; P < 0.05). This may indicate local cell activation,
      since the alveolar capillary membrane probably was intact, as indicated by an
      unaffected albumin concentration. The observed changes in the deep airways are
      probably caused by exposure to smoke. It cannot be concluded whether these
      changes are permanent or are part of a natural temporary defense mechanism.

PMID- 9258386
TI  - Interaction of genetic and exposure factors in the prevalence of berylliosis.
AB  - Prevalence of berylliosis, a lung disorder driven by the activation of beryllium
      specific T cells, is associated with a major histocompatibility complex (MHC)
      class II marker (HLA-DPB1Glu69) and with the type of industrial exposure. We
      evaluated the interaction between marker and exposure in a beryllium-exposed
      population in which the prevalence of berylliosis was associated with machining
      beryllium. The presence of the marker was associated with higher prevalence (HLA
      DPB1Glu69-positive machinists 25%; HLA-DPB1Glu69-negative machinists 3.2%, P =
      0.05) and predicted berylliosis independent of machining history (odds ratios
      11.8 and 10.1). The study shows that in berylliosis the carrier status of a
      genetic susceptibility factor adds to the effect of process-related risk factors.

PMID- 9258387
TI  - Radiographic asbestosis is not a prerequisite for asbestos-associated lung cancer
      in Ontario asbestos-cement workers.
AB  - In recent years, controversy has developed about whether pre-existing asbestosis
      is a prerequisite for the diagnosis of asbestos-related lung cancer. This paper
      presents the results of a prospective study, in a cohort of Ontario asbestos
      cement workers, of lung cancer in relation to radiographs obtained 20 and 25
      years from first exposure to asbestos. Radiographs were interpreted by a single
      NIOSH-certified "B" reader, and asbestosis was defined to mean an ILO code of 1/0
      or greater. There were 143 subjects (123 without asbestosis, 20 with asbestosis),
      with a radiograph available for interpretation at 20 years from first exposure or
      later. The lung cancer standardized mortality ratio (SMR) among men without
      asbestosis at 20 years latency was 5.53 (95% CI: 2.9-9.7). There were 128
      subjects (114 without asbestosis, 14 with asbestosis) with a radiograph available
      for interpretation at 25 years from first exposure or later. The lung cancer SMR
      among men without asbestosis at 25 years latency was 5.81 (95% CI 2.7-11). The
      results of this study are consistent with those of epidemiologic studies of
      asbestos-exposed populations in a variety of exposure situations. These studies
      have demonstrated that lung cancer risk is elevated in the presence of
      radiographic asbestosis, but they have also shown that lung cancer risk may be
      elevated in the absence of radiographic asbestosis.

PMID- 9258388
TI  - Assessment of past exposure to man-made vitreous fibers in the Swedish
      prefabricated house industry.
AB  - Large quantities of man-made vitreous fibers (MMVF) are handled in the Swedish
      prefabricated wooden house industry. The present study is part of a program to
      investigate mortality, cancer incidence, and current as well as previous exposure
      to MMVF among workers in the Swedish prefabricated wooden house industry. Since
      measurements of historical fiber exposure levels are lacking, these were
      calculated by the application of a matrix of multipliers to recently measured
      MMVF levels. The multipliers represented changes over time in production rate,
      technical properties of the fibers, manual handling vs. automation, and
      ventilation control. The multipliers were based on a similar matrix, developed
      for the MMVF-manufacturing industry, which was modified to reflect the conditions
      in the wooden house industry. The model was developed for the highest-exposed job
      title in the study, insulators. One hundred and twenty samples of airborne fiber
      were taken in 11 plants to reflect current exposure levels. The highest mean
      fiber exposure level for insulators was assessed as 0.18 f/ml (geometric mean),
      which occurred during the mid-1970s, compared to 0.10 f/ml at the end of the
      1980s and the early 1960s. Changes in production rate, improved ventilation
      control, and the surface area of the total amount of MMVF sheets handled per
      insulator were the most important variables of the model. No increased risk of
      lung cancer was found in the present industry.

PMID- 9258389
TI  - The relation between subjective dust exposure estimates and quantitative dust
      exposure measurements in California agriculture.
AB  - Measuring exposure levels for epidemiologic research is time consuming and
      expensive and therefore subjective exposure estimates are sometimes used instead.
      In this study we related the subjective dust exposure estimates of workers in
      California agriculture to personal dust exposure measurements. One hundred and
      twenty-four observations were available for comparison of subjective dust
      estimates and inhalable dust measurements and 129 observations for comparison of
      subjective dust estimates and respirable dust measurements. Individual subjective
      dust estimates showed weak to moderate correlations with measured dust
      concentrations for both the inhalable (Rs = 0.67) and respirable dust fraction
      (Rs = 0.36). The within-worker reliability coefficients were low (0.2 and 0.1,
      respectively). Grouped subjective dust estimates performed better and showed a
      consistent increase with average measured dust levels, in particular for the
      inhalable dust fraction (R2 = 0.81). Age, the number of years working in
      agriculture, education level, the presence of any respiratory symptoms, and the
      language of the questionnaire did not have a significant independent effect on
      the relationship between measured dust levels and subjective dust estimates.
      California agricultural workers appear to be reasonably good at estimating
      inhalable dust levels, in particular if an average of many different workers is
      taken, but they are unable to provide good estimates of respirable dust levels.
      Measuring dust levels remains the preferred option.

PMID- 9258390
TI  - Agreement between company-recorded and self-reported estimates of duration and
      frequency of occupational fumigant exposure.
AB  - Investigators must often rely on self-reported work history information collected
      with questionnaires. However, little is known about the agreement between self
      reported estimates of exposure and records kept by companies. As part of a cross
      sectional medical study of structural fumigation workers, self-reported work
      history information was collected on both duration and frequency of exposure
      using an interviewer-administered questionnaire. All company records available on
      these workers were also collected. Only 15 of 81 structural fumigation companies
      identified by study participants as current or past structural fumigation
      employers had records suitable for comparison. These 15 companies employed 32 of
      the workers who participated in the cross-sectional medical study. The exposure
      information provided by the 32 workers was compared to information obtained from
      company records. By examining the agreement between these two data sources,
      potential limitations were identified in both the self-reported and company
      recorded exposure data. By recognizing these limitations in the exposure data, we
      identified the most appropriate exposure measures to be used in subsequent data
      analyses. This exercise also demonstrated the difficulties in undertaking these
      exposure comparisons in an industry consisting of many small, independent
      companies. Similar difficulties with assessing exposures may be experienced by
      investigators studying other service industries consisting of many small,
      independent companies (e.g., dry cleaning, auto repair).

PMID- 9258391
TI  - Semen quality and fertility of men employed in a South African lead acid battery
      plant.
AB  - Previous studies of the associations of measures of occupational lead exposure
      with measures of semen quality and infertility among male workers have produced
      conflicting results. The current study was undertaken to examine these
      associations among a population of workers with a broad range of measures of
      current and historical lead exposure. Ninety-seven lead-exposed workers from a
      South African lead acid battery facility provided semen samples that were
      analyzed for sperm density, sperm count, sperm motility, sperm morphology, and
      presence of antisperm antibodies. Questionnaire data were collected for reported
      histories of sub- or infertility. Current blood leads ranged from 28 to 93
      micrograms/dl. Semen lead ranged from 1 to 87 micrograms/dl. Reasonably
      consistent and significant associations were found between an increased
      percentage of sperm with abnormal morphology and higher measures of current blood
      lead, cumulative blood lead, and duration of exposure. An increased percent of
      immotile sperm was associated only with zinc protoporphyrin (ZPP) among the lead
      exposure measures. There were no associations of sperm density or sperm count
      with any of the lead exposure measures. A weak association of increased percent
      of sperm with antisperm antibodies with increased semen lead was present. There
      were no consistent associations of measures of lead exposure with measures of
      fertility or procreativity. This study, while supporting the association of lead
      exposure with increased risk of abnormal sperm morphology seen in some previous
      studies, does not lend support to previously reported associations of sperm
      density or count or infertility with measures of lead exposure. However, the
      relatively high range of current blood leads, high prevalence of abnormalities in
      semen quality, and the lack of a control population, suggest that these negative
      findings should be interpreted with caution.

PMID- 9258392
TI  - Case-control study of malignant melanoma among employees of the Lawrence
      Livermore National Laboratory.
AB  - During 1972 to 1977, the Lawrence Livermore National Laboratory (LLNL)
      experienced increased diagnosis of malignant melanoma among employees. In 1984, a
      report on the results of a case-control study of 39 cases concluded that
      occupational factors, including exposures to ionizing radiation and to chemicals,
      caused the excess incidence. The study reported here, based on results from 69
      case-control pairs, re-examines the role of the occupational factors implicated
      by the earlier study in melanoma causation. Results from this study suggest that
      constitutional factors, including skin reactivity to sunlight, sunbathing
      frequency, and number of moles, explain most of the excess melanoma. Exposures to
      occupational factors, including ionizing radiation and chemicals, were found to
      be no different in cases than in controls.

PMID- 9258393
TI  - Lymphoma and multiple myeloma mortality in relation to magnetic field exposure
      among electric utility workers.
AB  - Associations between occupational magnetic field exposure and non-Hodgkin's
      lymphoma (NHL), Hodgkin's disease, and multiple myeloma mortality were evaluated
      in 138,905 electrical utility workers. A job-exposure matrix based on measured
      magnetic fields was used to derive individual exposure estimates. There was a
      small positive association between all NHL and low-grade NHL and duration of
      employment in any magnetic field-exposed job, but only up to 20 years. Cumulative
      magnetic field exposure was associated with a rising, then falling, risk of NHL.
      Rate ratios for intermediate/high-grade lymphoma were increased for the highest
      levels of lifetime cumulative exposure (RR = 3.7 and RR = 2.3), and were most
      pronounced for those exposures occurring 10-20 years previously. Hodgkin's
      disease and multiple myeloma mortality did not appear to be associated with
      exposure. Associations were stronger for NHL subgroups, suggesting that further
      analysis by subgroup may be warranted, but the absence of dose-response gradients
      diminishes the likelihood that associations represent causal relationships.

PMID- 9258394
TI  - Exposure to video display terminals and risk of spontaneous abortion.
AB  - Clusters of spontaneous abortion among video display terminal (VDT) users in
      North America and Canada in the late 1970s aroused suspicion about the potential
      risk of an association between VDT. exposure and pregnancy outcome. This case
      control study considered the association between VDT use and the risk of
      miscarriage. Cases were 508 women admitted for spontaneous abortion to the
      Clinica Luigi Mangiagalli and a network of obstetric departments in the Milan
      area. Controls were 1,148 women who gave birth at term to healthy infants on
      randomly selected days at the same hospitals where cases were identified. No
      association emerged between VDT exposure and spontaneous abortion, the estimated
      odds ratio being 1.0 (95% CI: 0.8-1.2). This evidence agrees with studies
      conducted in different countries by various authors.

PMID- 9258395
TI  - Study of respirator effect on nasal-oral flow partition.
AB  - Factors affecting worker tolerance of respiratory personal protective devices are
      inadequately understood. This study evaluates whether respirator-type loads
      affected the switch from nasal to oral breathing. Eleven healthy subjects were
      studied under progressive exercise conditions, using a respirator full-face mask
      with inspiratory resistance (I), pressure breathing (P) (10 cm H2O end-expiratory
      pressure), or no load (N). A rapid-response thermistor was used to determine
      whether flow was predominantly oral or nasal. Both P and I increased the
      percentage of time that breathing was predominantly oral. The effect was most
      pronounced at higher exercise levels. The percentage of mouth breathing appeared
      to be closely related to the expiratory time. This study suggests that nasal-oral
      flow partitioning should be considered as a possible determinant of respirator
      tolerance.

PMID- 9258396
TI  - Polychlorinated naphthalene exposures and liver function changes.

PMID- 9258397
TI  - Right-to-know training of workers with IQ less than 70: a pilot study.
AB  - Chemical emergencies occur frequently in the workplace. Laws and regulations have
      been enacted to reduce the risk of injuries to workers, including workers with an
      IQ less than 70. These regulations require employers to educate their workers
      about the nature and hazards of toxic substances in the workplace, about methods
      to reduce exposure, and about appropriate responses in case of an accident or an
      emergency. From May to August 1996, a project examined the responses of 58
      Goodwill Industries employees before and after their attendance at a mandatory
      "Right-to-Know" training program. Responses to five questions relating to the
      safe use of chemicals were analyzed. A combination of quantitative and
      qualitative evaluations determined that for the 28 subjects with IQ < 70, the
      program did not achieve its goals. However, the program did provide fuller
      information for the 30 subjects with IQ > or = 70. The findings of this pilot
      study show the need to develop training programs tailored to meet the needs and
      conditions of workers with IQ < 70.

PMID- 9258398
TI  - Bronchial reactivity in oil-mist exposed automobile workers revisited.

PMID- 9258399
TI  - Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.
AB  - A workshop discussing eight clusters of hypersensitivity pneumonitis in the
      automotive industry among metalworking fluid-exposed workers concluded that a
      risk exists for this granulomatous lung disease where water-based fluids are used
      and unusual microbial contaminants predominate. Strong candidates for microbial
      etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity
      pneumonitis occur among cases with other work-related respiratory symptoms and
      chest diseases. Reversibility of disease has occurred in many cases with exposure
      cessation, allowing return to work to jobs without metalworking fluid exposures
      or, in some situations, to jobs without the same metalworking fluid exposures.
      Cases have been recognized with metalworking fluid exposures generally less than
      0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk
      factors, exposure-response relationships, intervention efficacy, and natural
      history, as well as surveillance needs to define the extent of the problem in
      this industry. In the absence of answers to these questions, guidance for
      prevention is necessarily limited.

PMID- 9258401
TI  - Relationship between endothelial cell turnover and permeability to horseradish
      peroxidase.
AB  - The quantitative relations between cell turnover (cell mitosis and death) and
      macromolecular leakage were studied at the level of individual endothelial cells
      (ECs) in the thoracic aortae of 32 adult male Sprague-Dawley rats. The
      experiments were performed on en face preparations of aortic specimens obtained
      1, 3, 5 or 10 min after the intravenous administration of horseradish peroxidase
      (HRP). Mitotic ECs were identified by hematoxylin nuclear staining; dying or dead
      ECs containing cytoplasmic immunoglobulin G were detected by indirect
      immunocytochemistry and endothelial leakages to HRP were visualized by light
      microscopy. The number and size of HRP spots increased with time and the spots
      fused to form large brown areas in 10 min. Quantitative data on the contributions
      of EC mitosis and EC death to the transendothelial leakages of HRP were obtained
      in the same animals. Although mitotic ECs (0.01%) and dying ECs (0.1%) were
      infrequent in occurrence, the great majority (over 90%) of these ECs were
      associated with focal HRP uptake. These mitotic and dying ECs, however, accounted
      for only 17% of the total leakage sites indicating that significant leakage of
      the 4-5 nm HRP also occurs in normal ECs not morphologically identified as being
      in mitosis or death. The percentages of leaky spots attributable to mitosis or
      cell death were greater for the 6 nm albumin and the 22 nm low density
      lipoprotein (LDL) which probably cannot traverse the normal junctions and use the
      leaky junctions during cell turnover as the major pathway.

PMID- 9258400
TI  - Pathophysiological implication of the structural domains of lipoprotein(a).
AB  - Numerous epidemiological studies have shown that lipoprotein(a) (Lp(a)) is an
      independent risk factor for the premature development of cardiovascular disease.
      In spite of such evidence, the structural and functional features of this
      atherogenic, cholesterol-rich particle are not clearly understood. We have
      demonstrated the presence of two distinct structural domains in apolipoprotein(a)
      (apo(a)), which are linked by a flexible and accessible region located between
      kringles 4-4 and 4-5. We have isolated the Lp(a) particle following removal of
      the N-terminal domain by proteolytic cleavage; the residual particle, containing
      the C-terminal domain (comprising the region from Kr 4-5 to the protease domain),
      is linked to apo B-100 by disulphide linkage, and is termed 'mini-Lp(a)'. Mini
      Lp(a) exhibited the same binding affinity to fibrin as the corresponding Lp(a).
      This finding indicated that the kringles responsible for fibrin binding are
      restricted to Kr 4-5 to Kr 4-10, an observation consistent with the failure of
      the N-terminal domain to bind to fibrin. N-terminal fragments of apo(a) have been
      detected in the urine of normal subjects, thereby indicating that part of the
      catabolism of Lp(a), which is largely indeterminate, could occur via the renal
      route.

PMID- 9258402
TI  - Cholesterol efflux in vivo from a depot of cationized LDL injected into a thigh
      muscle of small rodents.
AB  - We have developed a model system to measure quantitatively removal of cholesterol
      from a well-defined depot in vivo. To that end, lipoproteins were injected into
      the rectus femoris muscle of small rodents, using a 25 microliters Hamilton
      syringe and a 27-gauge needle. In most experiments, the injected volume was 10
      microliters containing 200 micrograms of cholesterol. The lipoproteins tested
      were native or modified LDL labeled with trace amounts of [3H]free cholesterol
      ([3H]FC). The amount of label or of cholesterol mass recovered at various time
      intervals after injection was normalized to that found after 10 min (designated
      time 0). In mice, the highest recovery of the [3H]cholesterol 24 h after
      injection was found with cationized LDL, and ranged between 78% and 84%, whereas
      retention of native LDL did not exceed 24%. Based on results of 9 experiments
      with cationized LDL, the loss of [3H]FC was mono-exponential between 1 and 14
      days and the t1/2 was about 4 days. The disappearance curve of cholesterol mass
      showed an initial slow and a later more rapid component, the latter with a t1/2
      of 4 days. The initial lag is most probably due to the presence of cholesteryl
      ester, which needs to be hydrolyzed prior to egress. This assumption was verified
      by injection of cat-LDL labeled with [3H]cholesteryl oleate and finding a similar
      lag as well as evidence of [3H]cholesteryl ester hydrolysis. Histological
      examination of the injected muscle 1-4 days after injection of cat LDL showed
      infiltration with mononuclear cells in an area limited to the site of injection.
      The presently described model system, which mimics to some extent events
      occurring during atherogenesis, permits quantitative evaluation of egress of
      deposited cholesterol and may allow to study the role of HDL in such a process.

PMID- 9258403
TI  - Interleukin-2 modulates the responsiveness to angiotensin II in cultured vascular
      smooth muscle cells.
AB  - Preincubation with interleukin-2 (IL-2), a T cell-derived cytokine, enhanced the
      increase in intracellular Ca2+ ([Ca2+]i) induced by angiotensin II (AII) in
      vascular smooth muscle cells (VSMC). IL-2 itself did not affect the basal [Ca2+]i
      level or the maximal response of [Ca2+]i increase induced by AII. Furthermore, IL
      2-induced enhancement was not observed in the absence of extracellular Ca2+,
      suggesting that IL-2 enhances Ca2+ influx induced by AII. IL-2 also enhanced the
      stimulation of DNA synthesis induced by AII, although IL-2 alone did not
      stimulate DNA synthesis. Genistein, an inhibitor of protein tyrosine kinases,
      significantly inhibited IL-2-induced enhancement of both Ca2+ influx and DNA
      synthesis induced by AII. A neutralizing antibody against heparin-binding
      epidermal growth factor-like growth factor (HB-EGF) partially inhibited IL-2
      induced enhancement of DNA synthesis induced by AII. These findings suggest that
      autocrine HB-EGF is partially involved in the mechanism of IL-2-induced
      enhancement of DNA synthesis. On the other hand IL-2 stimulated both
      glycosaminoglycan (GAG) and prostacyclin syntheses and enhanced the stimulation
      of both GAG and prostacyclin syntheses induced by AII. Therefore, IL-2 may play
      important roles in the pathogenesis of atherosclerosis and vascular disease by
      modulating the responsiveness to AII in VSMC.

PMID- 9258404
TI  - Oxidized low density lipoprotein and very low density lipoprotein enhance
      expression of monocyte chemoattractant protein-1 in rabbit peritoneal exudate
      macrophages.
AB  - The migration of monocytes into arterial subendothelial space is one of the
      earliest events in atherogenesis. Monocyte chemoattractant protein 1 (MCP-1) is a
      potent monocyte chemoattractant. The purpose of this work was to examine whether
      oxidized low density lipoprotein (OX-LDL) and very low density lipoprotein (OX
      VLDL) have any effect on the expression of MCP-1 mRNA and protein in rabbit
      peritoneal exudate macrophages. The total RNA was extracted from the macrophages
      after 24 h exposure to LDL, VLDL, OX-LDL, and OX-VLDL, respectively, and the
      media (LDL-CM, VLDL-CM, OX-LDL-CM and OX-VLDL-CM) conditioned by the macrophages
      exposed to the above-mentioned lipoproteins were collected. The MCP-1 mRNA
      expression in macrophages was examined by Northern blot analysis. Meanwhile, MCP
      1 protein in the conditioned media was determined by sandwich ELISA. The
      chemotactic activity of the conditioned media for monocytes was determined by
      micropore filter assay. The results revealed that the macrophages can express MCP
      1, and 24 h exposure to OX-LDL and OX-VLDL induced a 3.2-fold and a 3.4-fold
      increase in MCP-1 mRNA expression in macrophages and a 2.2-fold and a 2.5-fold
      increase in the level of MCP-1 protein in the conditioned media, respectively.
      However, 24 h exposure to LDL and VLDL only induced a slight increase in the
      expression of MCP-1 mRNA and protein in macrophages. Furthermore, the migration
      distance of monocyte induced by OX-LDL-CM and OX-VLDL-CM was longer than that
      induced by LDL-CM and VLDL-CM, as well as by CM. We conclude that the macrophages
      can express MCP-1, and OX-VLDL and OX-VLDL induce stronger MCP-1 expression. It
      suggests that macrophages may amplify the recruitment into subendothelial space,
      and OX-LDL and OX-VLDL may play an important role in the pathogenesis of
      atherosclerosis through enhancing the MCP-1 expression in macrophages.

PMID- 9258405
TI  - Inhibitory effects of bromocriptine on vascular smooth muscle cell proliferation.
AB  - Bromocriptine (BC), an ergot alkaloid with wide therapeutic use in humans, has
      been shown to inhibit proliferation of several abnormally hyperproliferative
      cells in vivo and in vitro. In the present study, direct effects of BC on mitogen
      stimulated proliferation of rat vascular smooth muscle cells (VSMC) (A7r5 cells)
      and human aortic smooth muscle cells (HAOSMC) were examined in vitro. Twenty-four
      hour proliferative responses of quiescent A7r5 cells and HAOSMC to a variety of
      mitogens in the presence or absence of BC were determined by quantifying the
      incorporation of 3H-thymidine into DNA. BC at 1 microM inhibited the responses of
      A7r5 cells to various concentrations of fetal calf serum (FCS) by 50-70% without
      affecting the ED50 of FCS (2%). BC dose dependently inhibited the proliferation
      of A7r5 cells and HAOSMC stimulated by 2% FCS, with 52% inhibition at 1 and 0.1
      microM, respectively. BC at 1 microM also completely inhibited the maximal
      mitogenic responses of A7r5 cells to prolactin, platelet-derived growth factor,
      insulin-like growth factor, and phorbol mysterate acetate (PMA), and BC at 1
      microM completely inhibited the mitogenic response of HAOSMC to PMA. BC is a
      dopamine D2 agonist, a noradrenergic alpha 2 agonist, and an .alpha 1 antagonist,
      but the inhibitory effects of BC on A7r5 cell proliferation could not be mimicked
      by the specific D2 agonists, LY162502 and LY171555; the alpha 2 agonist,
      clonidine; or the alpha 1 antagonist, WB-4101. Neither dopamine nor the D2
      agonist, LY162502, could inhibit HAOSMC proliferation induced by FCS. The PMA
      induced stimulation of protein kinase C (PKC), a positive regulator of
      mitogenesis, could be completely blocked in A7r5 cells and HAOSMC by 1 and 0.1
      microM BC, respectively. However, FPCS (2%)-induced activation of PKC in A7r5
      cells and HAOSMC could only be blocked by 61 and 19% by BC (1 microM for A7r5
      cells and 0.1 microM for HAOSMC), respectively. Given the existing evidence that
      BC reduces the severity of several other pathological conditions, such as insulin
      resistance, inflammation, and hyperlipidemia, which potentiate vascular disease,
      the current findings further suggest that BC use in the treatment of
      atherosclerosis and/or restenosis deserves further investigation.

PMID- 9258406
TI  - 1 alpha,25-dihydroxyvitamin D3 induces very low density lipoprotein receptor mRNA
      expression in HL-60 cells in association with monocytic differentiation.
AB  - Expression of VLDL receptor mRNA during differentiation of HL-60 cells was
      investigated by Northern analysis. The expression induced in 1 alpha,25
      dihydroxyvitamin D3 (1 alpha,25(OH)2D3)-treated cells was 3 times that in
      untreated cells, while LDL receptor mRNA expression was unchanged. VLDL receptor
      mRNA levels were not changed in macrophages caused to differentiate from HL-60
      cells by treatment with phorbol 12-myristate 13-acetate (PMA). Treatment of
      sarcoma cells which possess the vitamin D receptor (MG-63 cell line) with 1
      alpha,25(OH)2D3 did not affect VLDL receptor mRNA levels. Therefore, 1
      alpha,25(OH)2D3 induces VLDL receptor mRNA in HL-60 cells through differentiation
      dependent mechanisms.

PMID- 9258407
TI  - HMG-CoA reductase inhibitors suppress macrophage growth induced by oxidized low
      density lipoprotein.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ameliorate
      atherosclerotic diseases in several models of vascular disease. This is largely
      due to their ability to reduce plasma cholesterol levels in vivo. Proliferation
      of cellular components is one of the major events in the development and
      progression of atherosclerotic lesions. We recently demonstrated that oxidized
      low density lipoprotein (Ox-LDL), a likely atherogenic lipoprotein present in
      vivo, is capable of inducing macrophage growth in vitro. In the present study, we
      investigated the effect of HMG-CoA reductase inhibitors, simvastatin and
      pravastatin, on Ox-LDL-induced macrophage growth. Our results demonstrated that
      these inhibitors effectively suppressed Ox-LDL-induced macrophage growth with
      concentrations required for 50% inhibition by simvastatin and pravastatin being
      0.1 and 80 microM, respectively, and that this inhibitory effect was reversed by
      mevalonate but not by squalene. Under these conditions, simvastatin did not
      affect the endocytic degradation of Ox-LDL, nor subsequent accumulation of
      intracellular cholesteryl esters. Our results suggest that a non-cholesterol
      metabolites(s) of mevalonate pathway may play an important role in Ox-LDL-induced
      macrophage growth. Since it is well known that macrophage-derived foam cells are
      the key cellular element in the early stage of atherosclerosis, a significant
      inhibition of Ox-LDL-induced macrophage growth by HMG-CoA reductase inhibitors in
      vitro, particularly simvastatin, may also explain, at least in part, their anti
      atherogenic action in vivo.

PMID- 9258409
TI  - Plasminogen activator inhibitor-1, the acute phase response and vitamin C.
AB  - Epidemiologial studies suggest that elevated plasma plasminogen activator
      inhibitor-1 (PAI-1) activity is associated with ischaemic heart disease. Based on
      our earlier work suggesting a link between plasma fibrinogen, infection and low
      vitamin C status, we sought to determine whether similar relationships existed
      for PAI-1 activity. We performed a longitudinal study of cardiovascular disease
      risk factors in 96 volunteers aged 65-74 years, living in the community in
      Cambridge. Each subject was visited at home 7 times over a 14 month period.
      Plasma PAI-1 activity, serum ascorbate, markers of the acute phase response,
      serum lipids and other cardiovascular disease risk factors were measured on each
      occasion. In a multiple regression analysis, the three significant predictors of
      PAI-1 activity were body mass index (P = 0.0001), blood neutrophil count (P =
      0.03) and, inversely, serum ascorbate (P = 0.003). The inverse relationship
      between PAI-1 activity and serum ascorbate persisted even when vitamin C
      supplement takers or smokers were excluded from the analysis. Serum ascorbate was
      strongly related to estimated dietary intake of vitamin C (P < 0.0001). Low serum
      ascorbate is associated with high PAI-1 activity which is, in turn, associated
      with increased ischaemic heart disease risk. We hypothesise that activation of
      the acute phase response by infection could increase PAI-1 activity and,
      consequently, also increase the risk of coronary artery thrombosis. Furthermore,
      we suggest that vitamin C could attenuate this response.

PMID- 9258408
TI  - G1 phase arrest of human smooth muscle cells by heparin, IL-4 and cAMP is linked
      to repression of cyclin D1 and cdk2.
AB  - Smooth muscle cell proliferation is a key event in the development of
      atherosclerosis. Inhibition of this proliferation may lead to better prevention
      and treatment of the disease. While a number of agents have been found to inhibit
      SMC proliferation, their mechanisms of action are not fully understood. We wanted
      to determine the effects of three physiologically relevant anti-mitogenic agents
      on two classes of proteins which have major roles in cellular proliferation,
      namely cyclins and cyclin-dependent kinases (cdks). Following stimulation with
      fetal calf serum (FCS), quiescent human umbilical artery smooth muscle cells
      (HUASMC) synthesised cyclin D1 mRNA and protein and cdk2 mRNA in the G1 phase,
      whereas cdc2 protein was expressed after the onset of the S phase. Heparin, a
      strong inhibitor of HUASMC proliferation, strongly down-modulated the levels of
      cyclin D1 mRNA and protein, cdk2 mRNA and cdc2 protein. Interleukin-4 (IL-4) or 8
      bromo-adenosine 3',5'-cyclic monophosphate (cAMP) also lowered the levels of
      these cell cycle regulatory proteins, although their effects were relatively
      weak, reflecting their only partial inhibition of HUASMC DNA synthesis. There was
      specificity in the cell cycle targets of the agents since none appeared to affect
      the levels of cdk4 protein.

PMID- 9258410
TI  - Effects of nitric oxide and superoxide on relaxation in human artery and vein.
AB  - Endothelium-derived relaxing and contracting factors play an important role in
      atherosclerosis, re-stenosis and graft survival. Internal thoracic artery (ITA)
      and saphenous vein (SV) are used as conduit vessels in coronary artery bypass
      graft surgery (CABG). The long-term graft patency rate is higher with ITA than
      SV. Effects of nitric oxide and superoxide on vascular relaxation in isolated
      rings of ITA and SV from patients undergoing CABG were investigated. NG-nitro-L
      Argenine methylester (L-NAME) was used to block nitric oxide synthesis and
      superoxide dismutase (SOD) and tiron to scavenge superoxide. Responses to
      carbachol were taken as a measure of stimulated nitric oxide release and
      increased responses to phenylephrine after addition of L-NAME as a measure of
      basal nitric oxide release. Immunocytochemical demonstration of endothelial
      nitric oxide synthase was performed using anti-endothelial nitric oxide
      synthetase (anti-eNOS) NOS antibody. Stimulated nitric oxide release was observed
      in ITA and SV but basal release was reduced or absent in SV. Treatment with SOD
      and tiron potentiated carbachol stimulated relaxation in ITA and SV. Tiron
      treatment resulted in a significant increase in basal nitric oxide in veins. eNOS
      immunoreactivity was more intense in ITA than SV, compatible with reduced nitric
      oxide production in veins. This may contribute to the reduced patency of venous
      grafts.

PMID- 9258411
TI  - Transformation of high density lipoprotein 2 particles by hepatic lipase and
      phospholipid transfer protein.
AB  - High density lipoprotein 2 (HDL2) was incubated with phospholipid transfer
      protein (PLTP) or with hepatic lipase (H-TGL), and the incubation products were
      separated into a d < 1.22 g/ml and a d > 1.22 g/ml fractions. The d < 1.22 g/ml
      fraction produced by PLTP was larger, had lower apolipoprotein A-I and higher
      lipid and apolipoprotein A-II content than native HDL2. The d > 1.22 g/ml
      fraction represented 30% of the initial HDL2 protein and consisted of small,
      apolipoprotein A-I and phospholipid-rich particles, with a high
      sphingomyelin:phosphatidylcholine ratio. Incubation with H-TGL led to a d < 1.22
      g/ml fraction which was comparable to native HDL2 regarding size and chemical
      composition. The d > 1.22 g/ml particles represented only 5% of the initial HDL2
      protein and had slightly higher diameter and sphingomyelin:phosphatidylcholine
      ratio than those produced by PLTP. Enrichment of HDL2 with triglyceride prior to
      incubation increased the amount of protein released into the d > 1.22 g/ml
      fraction (20%) but had no effect on size and chemical composition of the
      particles. We conclude that PLTP and H-TGL promote the formation of small, pre
      beta-like HDL particles from HDL2.

PMID- 9258412
TI  - ACAT inhibitor HL-004 accelerates the regression of hypercholesterolemia in
      stroke-prone spontaneously hypertensive rats (SHRSP): stimulation of bile acid
      production by HL-004.
AB  - The effect of the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor HL-004 on
      bile acid production was studied during the regression phase of pre-established
      hypercholesterolemia in stroke-prone spontaneously hypertensive rats (SHRSP).
      These rats were fed a hypercholesterolemic diet containing 5% cholesterol, 2%
      cholic acid, and 20% suet for 30 days to induce hypercholesterolemia. The
      regression phase was started by switching the diet to normal chow, followed by
      another 30 days of the diet. The decrease in serum cholesterol level was
      accelerated by treatment with 0.09% HL-004. At the end of regression, hepatic
      ACAT activity was significantly lower in the HL-004 treated animals, an event
      concomitant with the significant decrease in cholesteryl ester content in the
      liver. In contrast hepatic cholesterol 7 alpha-hydroxylase activity was
      maintained at a higher level in the HL-004 treated animals. HL-004 increased the
      secretion of bile acid and biliary lipids in bile duct-cannulated SHRSP. In
      HepG2:cells, HL-004 at 1-30 microM dose-dependently stimulated bile acid
      synthesis from [3H]cholesterol. When cholesterol 7 alpha-hydroxylase activity of
      the liver was compared ex vivo in the presence and in the absence of exogenous
      cholesterol, it was suggested that the higher 7 alpha-hydroxylase activity of the
      HL-004 group could be attributed not only to expansion of the endogenous
      cholesterol pool, which may be the result of hepatic ACAT inhibition by HL-004
      but to the direct effect of HL-004 on bile acid production. Thus, HL-004
      accelerates the regression of hypercholesterolemia, an event which may be related
      to the stimulation of bile acid production in the liver.

PMID- 9258413
TI  - Gender differences and other determinants of the rise in plasma homocysteine
      after L-methionine loading.
AB  - The methionine load test is widely used to identify subjects with mild
      homocysteinemia. We studied factors influencing the rise in plasma homocysteine
      (tHcy) levels following oral methionine loading, after taking into account
      determinants of the basal level. The study population comprised 522 persons (mean
      age 53, range 17 to 95; 63% male; 60% with coronary disease). tHcy was measured
      fasting and 4 h after administration of L-methionine (dose 4 g/m2). The
      percentage rise in tHcy was greater in females, at younger ages, and with lower
      serum creatinine. Basal tHcy was lower in those with high levels of serum folate,
      red cell folate and serum B12; they also showed a greater percentage rise with
      loading. After adjustment for age, creatinine and serum vitamins the percent rise
      was greater in females (mean 230%, S.D. 92) than in males (mean 172%, S.D. 71, P
      < 0.0001). About 1/4 of this effect was explained by the methionine dose, but
      important independent gender effects remained. When the results of the loading
      test were compared with an overall reference range, females were systematically
      labelled as 'high' but comparison with age and gender-specific reference ranges
      normalised the sex distribution. Our data show that a single L-methionine loading
      protocol for both sexes is not appropriate. Gender-specific reference ranges
      should be used to define post-load homocysteinemia and previous studies which
      have identified a high proportion of females with this trait probably reflect the
      need for gender specific reference ranges.

PMID- 9258414
TI  - Lipoprotein(a) and HLA-DRB1 and -DQB1 genes in coronary artery disease.
AB  - In some respects, atherosclerosis resembles autoimmune disease. Since many
      autoimmune diseases are associated with certain histocompatibility leukocyte
      antigen (HLA) class II alleles, we have looked for a similar HLA association with
      atherosclerosis. In the first phase, genomic typing was performed in 52 men with
      coronary artery disease. In the second phase, 50 men with early onset (before 50
      years of age) coronary artery disease were studied. 12 DRB1 and 4 DQB1 alleles
      were determined by restriction fragment length polymorphism analysis. No
      significant difference in frequency of the examined alleles was observed in any
      of the patient groups compared to healthy controls. The plasma level of
      lipoprotein(a) (Lp(a)) is considered an important risk factor for early coronary
      heart disease. A linkage between inherited high levels of Lp(a) and certain HLA
      class II genotypes has been suggested. In the present study, Lp(a) levels were
      measured in men with early onset of coronary artery disease. 11 (23%) Study
      patients and 3 (7%) control subjects had Lp(a) levels above 450 mg/l. However, no
      correlation between high Lp(a) levels and certain HLA genotypes was found.
      Summarized, these findings indicate that atherosclerosis, especially early onset
      coronary atherosclerosis, is not a disease associated with particular HLA
      alleles.

PMID- 9258415
TI  - The effect of growth hormone replacement therapy for up to 12 months on
      lipoprotein composition and lipoprotein(a) in growth hormone-deficient adults.
AB  - The effect of growth hormone replacement therapy in near physiological doses on
      lipoprotein composition and serum lipoprotein(a) concentrations was investigated
      in growth hormone-deficient subjects. A randomised, double-blind, placebo
      controlled trial of recombinant growth hormone was undertaken for 6 months
      followed by an open extension for a further 6 months (0.125 IU/kg per week for
      the first 4 weeks of each 6 month period and thereafter 0.25 IU/kg per week). A
      total of 18 patients with isolated growth hormone deficiency or hypopituitarism
      were studied. Lipid concentrations were estimated in lipoprotein fractions and
      protein concentrations were measured in low density lipoprotein (LDL). Glucose
      and glycated haemoglobin in blood and insulin, cholesterol, triglyceride,
      apolipoproteins A-I and B and lipoprotein(a) concentrations were measured in
      serum. In the placebo-controlled phase fasting blood glucose concentrations
      increased with growth hormone treatment from 5.0 +/- 0.2 to 5.8 +/- 0.2 mmol/l (P
      = 0.02) (mean +/- S.E.M.), although no significant changes were seen in lipids or
      lipoproteins. In the group receiving active treatment total serum cholesterol
      decreased from 6.0 +/- 0.4 to 5.2 +/- 0.3 mmol/l (P = 0.002) after 6 months, due
      to reduced LDL cholesterol concentrations. Low density lipoprotein protein
      concentrations fell (0.8 +/- 0.1 versus 0.7 +/- 0.1 g/l) (P = 0.005), and LDL
      phospholipid levels decreased from 0.9 +/- 0.1 to 0.7 +/- 0.1 mmol/l (P = 0.007).
      Serum cholesterol and LDL composition reverted to pre-treatment values by 12
      months. Fasting blood glucose remained above pre-treatment values (P = 0.036) and
      fasting insulin was significantly increased (P = 0.044). There was no effect of
      growth hormone therapy on serum triglyceride, apolipoprotein or lipoprotein(a)
      concentrations. In conclusion, growth hormone therapy with near physiological
      doses has no long term effects on serum lipoprotein(a) concentrations or
      lipoprotein composition.

PMID- 9258416
TI  - Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids,
      apolipoproteins and lipoprotein particles in patients with elevated serum
      cholesterol and triglyceride levels.
AB  - The effects of atorvastatin (lipitor) on cholesterol-rich and triglyceride-rich
      lipoproteins were evaluated in this multicenter trial. Following a 6-week
      baseline period, 47 patients with elevated cholesterol and triglyceride levels
      were treated with atorvastatin 10 mg once daily (QD) for the initial 12 weeks
      (Period 1) increasing to 20 mg QD for the following 12 weeks (Period 2). At both
      the 10 and 20 mg doses, atorvastatin treatment resulted in significant reductions
      compared to pretreatment levels in low-density lipoprotein cholesterol (LDL-C),
      total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C),
      apolipoprotein (apo) B, apoB in LDL (LDL-apo B), apo B in VLDL (VLDL-apo B),
      lipoprotein (Lp)B, lipoprotein B-complex (LpBc), triglycerides (TG), low-density
      lipoprotein triglycerides (LDL-TG), very low-density lipoprotein triglyceride
      (VLDL-TG), high-density lipoprotein triglycerides (HDL-TG), and apo C-III.
      Atorvastatin 10 and 20 mg QD also resulted in significant increases in high
      density lipoprotein cholesterol (HDL-C), apo AI, and LpAII:B:C:D:E. Due to its
      unique ability to normalize both cholesterol-rich and triglyceride-rich
      particles, atorvastatin is a promising candidate for monotherapy in a broad range
      of patients including those with varying degrees of hypercholesterolemia and
      hypertriglyceridemia.

PMID- 9258417
TI  - Retropharyngeal pain and swelling in a dog.

PMID- 9258418
TI  - Cervical diskospondylitis in two horses.

PMID- 9258419
TI  - Nasopharyngeal cryptococcosis.
AB  - Naturally occurring cryptococcosis in five cats, a dog and a koala is described.
      Involvement of the nasopharynx was documented in all patients, and nasopharyngeal
      mass lesions accounted for the major presenting complaints in four. Signs
      referable to nasopharyngeal disease included snoring, stertor, inspiratory
      dyspnoea and aerophagia. Diagnoses were made by caudal rhinoscopy using a
      retroverted flexible endoscope, vigorous orthograde flushing with saline, or at
      necropsy. Concurrent cryptococcal rhinitis was present in all cases, although
      involvement appeared limited to the caudal nasal cavity in most cases. Typical
      signs of nasal cavity disease, such as sneezing and nasal discharge, were often
      absent. Treatment of nasopharyngeal cryptococcosis should include physical
      dislodgement or debulking of lesion(s) to provide immediate alleviation of upper
      airway obstruction, followed by systemic antifungal therapy to eliminate residual
      infection from the nasal cavity. Infections caused by Cryptococcus neoformans var
      gattii accounted for a disproportionately large number of these cases.

PMID- 9258420
TI  - Squamous cell carcinoma of the lung in a dog.

PMID- 9258421
TI  - Jembrana disease.

PMID- 9258422
TI  - Acute cortisol responses of lambs castrated and docked using rubber rings with or
      without a castration clamp.
AB  - OBJECTIVE: To measure the plasma cortisol response in lambs castrated and docked
      by three different methods (ring castration and tail docking, ring and clamp
      castration and tail docking; ring and clamp castration and ring tail docking) for
      4 h after treatment. DESIGN: A physiological study with controls. PROCEDURE: A
      rubber ring was applied to the scrotum. Then the castration clamp was placed,
      distal to the ring, on each spermatic cord such that there was no overlap of the
      crush lines. RESULTS: There were no differences in the cortisol secretion of the
      lambs castrated and tail docked by the ring only and by the ring plus castration
      clamp methods. Using the castration clamp in addition to the ring on the tail had
      no effect on cortisol secretion. CONCLUSIONS: Using the castration clamp did not
      appear to reduce the cortisol response to ring castration and docking, as
      demonstrated elsewhere, because the areas of uncrushed tissue between the two
      castration clamp crush lines allowed nociception from ischemic scrotal tissue to
      be transmitted cranially via undamaged nerve fibers.

PMID- 9258423
TI  - Use of drama in teaching the human side of veterinary practice.
AB  - OBJECTIVE: To describe a teaching experiment in which fifth year veterinary
      students were given the opportunity, using dramatic scenarios, to consider ways
      of dealing with emotive issues relevant to veterinary practice, that demand good
      communication skills. DESIGN: Workshops were devised using dramatised scenarios
      of several critical incidents in practice, including euthanasia. A clinical
      psychologist and several veterinary practitioners participated in discussions.
      Both live performances and video scenarios were presented to fifth year
      veterinary students and were followed by group discussions. Each workshop was
      evaluated and modifications were made where necessary. RESULTS: The teaching
      format involving drama was well received. The combination of drama and discussion
      was more effective than a formal talk and discussion, provoking animated
      participation and maintaining audience attention. The majority of students
      considered that comments and advice from attending veterinarians were the most
      useful part of the workshops in preparing them for veterinary practice. The large
      audience (up to 45 attendees) was considered to be desirable for enhancing
      discussion. Requests for more similar sessions were made by students. CONCLUSION:
      Drama was found to be a satisfactory modality in teaching communication skills in
      preparing veterinary students for practice.

PMID- 9258424
TI  - Organophosphorus residues in wool grease resulting from specified on-farm lice
      and flystrike control treatments.
AB  - OBJECTIVE: To investigate wool organophosphorus concentrations resulting from a
      range of farm pesticide application methods. DESIGN: Random sampling of wool for
      pesticide residues and on-farm interviews to determine associated treatments.
      PROCEDURE: Tasmanian fleece wool lots were sampled at random and tested for
      organophosphorus residues. The grower was identified and the pesticide treatments
      applied to the sheep were ascertained by on-farm interview. RESULTS: The residue
      concentrations showed a large variation that was not accounted for by differences
      in treatments by growers. Organophosphorus concentrations were proportional to
      the number of treatments applied, and inversely related to the time between
      pesticide application and the subsequent shearing, and were significantly
      influenced by the method of application. After allowing for the time of
      application, plunge dipping resulted in pesticide residue concentrations 2 to 2.5
      times greater than shower dipping, using spray races or hand jetting, and the use
      of these methods caused larger residues than the use of jetting races.
      CONCLUSIONS: We recommend that plunge or shower dipping should not be used more
      than 7 weeks after shearing, nor at higher concentration than the standard dose
      rate used for lice control, whereas jetting may be satisfactory for up to 7
      months after shearing, provided only one application is administered.

PMID- 9258426
TI  - Haematological findings in captive dolphins and whales.
AB  - OBJECTIVE: To examine haematological features in five species of healthy, captive
      marine mammals. ANIMALS: Twenty bottlenose dolphins (Tursips truncatus), seven
      Pacific white-sided dolphins (Lagenorhynchus obliquidens), five Risso dolphins
      (Grampus griseus) and five false killer whales (Pseudorca crassidens). RESULTS
      AND CONCLUSION: The red blood cell count was 4.21 x 10(12)/L in bottlenose
      dolphins, 5.32 x 10(12)/L in Pacific white-sided dolphins, 4.35 x 10(12)/L in
      Risso dolphins and 4.43 x 10(12)/L in false killer whales. The haemoglobin
      concentration was 1.51 g/L and packed cell volume 44.7% in bottlenose dolphins;
      the corresponding values were 1.71 g/L and 48.9% in Pacific white-sided dolphins,
      1.72 g/L and 49.4% in Risso dolphins, and 1.52 g/L and 47.8% in false killer
      whales. The white blood cell count was 7.097 x 10(9)/L in bottlenose dolphins,
      5.928 x 10(9)/L in Pacific white-sided dolphins, 5.001 x 10(9)/L in Risso
      dolphins and 7.921 x 10(9)/L in false killer whales. There were no significant
      differences in these values among bottlenose dolphins and Pacific white-sided
      dolphins. The proportion of eosinophils in the differential leukocyte count
      ranged from 10.3% to 11.5% in bottlenose dolphins, Pacific white-sided dolphins
      and false killer whales, but was only 0.4% in Risso dolphins. The eosinophilic
      granules were larger in Risso dolphins and false killer whales than in bottlenose
      and Pacific white-sided dolphins.

PMID- 9258425
TI  - Serum and mucosal antibody responses and protection in pigs vaccinated against
      Mycoplasma hyopneumoniae with vaccines containing a denatured membrane antigen
      pool and adjuvant.
AB  - OBJECTIVE: To investigate the protective efficacy of a pool of denatured membrane
      protein antigens of Mycoplasma hyopneumoniae (J strain) in the molecular size
      range 70 to 85 kDa (F3 antigen) in combination with adjuvants for pigs challenged
      with M hyopneumoniae. DESIGN: A vaccine efficacy experiment with assessment of
      serum and respiratory tract antibody responses. PROCEDURE: F3 antigens were
      emulsified with five different adjuvants. To groups of three pigs per vaccine,
      four vaccines were given by intramuscular injection, and two vaccines, including
      one of those given intramuscularly, were given by intraperitoneal injection.
      RESULTS: Compared to six unvaccinated pigs, animals vaccinated with F3 antigen
      displayed significantly reduced pneumonia (54% reduction in mean lung score)
      following experimental challenge. Analysis of post-vaccination, pre-challenge IgG
      and IgA ELISA antibody absorbances in serum and respiratory tract washings
      revealed no correlation with lung score. Six weeks after challenge, pigs
      previously vaccinated intramuscularly mostly demonstrated greater IgG and IgA
      responses in respiratory tract washings, and greater IgG serum antibody
      responses, than those vaccinated by intraperitoneal injection. CONCLUSION: Pigs
      vaccinated with M hyponeumoniae antigens in the molecular size range of 70 to 85
      kDa showed a significant reduction in lung lesions compared with unvaccinated
      control animals after experimental challenge. IgG and IgA antibody concentrations
      in serum and respiratory tract washings after vaccination do not provide a useful
      prognostic indicator of protection from enzootic pneumonia.

PMID- 9258427
TI  - Shifting paradigms: the hard road to acceptance of the contagion principle in
      Australia.

PMID- 9258428
TI  - Use of magnetic particles to improve the diagnosis of sheep-associated malignant
      catarrhal fever by polymerase chain reaction.

PMID- 9258429
TI  - Cytogenetic analysis of German shepherd dogs with haemophilia A.

PMID- 9258430
TI  - Some haematological values of Irish wolfhounds in Australia.

PMID- 9258431
TI  - Modes of treatment.

PMID- 9258432
TI  - Purification of active Escherichia coli ribosome recycling factor (RRF) from an
      osmo-regulated expression system.
AB  - Ribosome release factor (RRF) from Escherichia coli was overproduced from an osmo
      expression vector. More than 40% of cell protein was RRF after 6 h of induction.
      A purification scheme is described that produced 50 mg of RRF from an initial
      culture of 2 L. The recycling time for ribosomes synthesising the tripeptide fMet
      Phe-Leu in vitro in the absence of RF3 was reduced from 40 to 15 s by the
      addition of purified 1.5 microM RRF.

PMID- 9258434
TI  - Characterization of the sensitivity to various genotoxic agents of the UVU1-CHO
      cell line, a double mutant from UV complementation group 1.
AB  - The UVU1 CHO cell line, a double mutant of the excision repair complementation
      group 1 UV4 cell line was characterized by a higher UV sensitivity than its
      parent (Busch et al (1989) Mutagenesis 4, 349-354). We show here that this mutant
      is not affected in a UV mutagenic pathway. In addition, the UVU1 cell line is
      about two-fold more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine treatment
      than its parent without being more sensitive to cross-linking agents or ionizing
      radiations.

PMID- 9258433
TI  - Phosphorylation of Srp1p, the yeast nuclear localization signal receptor, in
      vitro and in vivo.
AB  - Srp1p, the protein encoded by SRP1 of the yeast Saccharomyces cerevisiae, is a
      yeast nuclear localization signal (NLS) receptor protein. We have previously
      reported isolation of a protein kinase from yeast extracts that phosphorylates
      Srp1p complexed with NLS peptides/proteins. From partial amino acid sequences of
      the four subunits of the purified kinase, we have now identified this protein
      kinase to be identical to yeast casein kinase II (CKII). It was previously
      thought that autophosphorylation of the 36 kDa subunit of the yeast enzyme was
      stimulated by the substrate, GST-Srp1p. However, with the use of a more refined
      system, no stimulation of autophosphorylation of the 36 kDa subunit of yeast CKII
      was observed. Biochemical and mutational analyses localized the in vitro
      phosphorylation site of Srp1p by CKII to serine 67. It was shown that, in the
      absence of NLS peptides/proteins, phosphorylation of the intact Srp1p protein is
      very weak, but deletion of the C-terminal end causes great stimulation of
      phosphorylation without NLS peptides/proteins. Thus, the CKII phosphorylation
      site is apparently masked in the intact protein structure by the presence of a C
      terminal region, probably between amino acids 403 and 516. Binding of NLS
      peptides/proteins most likely causes a change in protein conformation, exposing
      the CKII phosphorylation site. Mutational alterations of serine 67, the CKII
      phosphorylation site, to valine (S67V) and aspartic acid (S67D) were not found to
      cause any significant deleterious effects on cell growth. Analysis of in vivo
      phosphorylation showed that at least 30% of the wild type Srp1p molecules are
      phosphorylated in growing cells, and that the phosphorylation is mostly at the
      serine 67 CKII site. The ability of Srp1p purified from E coli and treated with
      calf intestinal phosphatase to bind a SV40 T-antigen NLS peptide was compared
      with that of Srp1p which was almost fully phosphorylated by CKII. No significant
      difference was observed. It appears that NLS binding does not require any
      phosphorylation of Srp1p, either by CKII or by some other protein kinase.

PMID- 9258435
TI  - The hog intestinal mucosa acylase I: subcellular localization, isolation, kinetic
      studies and biological function.
AB  - The soluble acylase I (N-acylamino acid amidohydrolase, EC 3.5.1.14) from hog
      intestinal mucosa was 11,000-fold purified for the first time using a new four
      step procedure involving an immunoaffinity chromatography. The resulting protein,
      which had an isoelectric point of 5.2 and a M(r) of 90,000 was composed of two
      apparently identical N-acylated polypeptide chains. Its amino acid composition
      was comparable to that of hog kidney acylase I. The enzyme had a pH optimum at
      8.0 and required Zn2+ or Co2+. The optimal temperature for the acylase reaction
      was 40 degrees C and the activation energy of thermodenaturation was estimated at
      260 kJ mol-1. The enzyme was strongly inhibited when preincubated with chelating
      agents, by diethyl pyrocarbonate under histidine-modifying conditions as well as
      by sulfhydryl compounds. The reaction of the purified enzyme with the synthetic
      substrate furylacryloyl-L-methionine was partly characterized as follows: Km =
      0.22 +/- 0.03 mM, kcat = 128.0 +/- 17.8 s-1 and kcat/Km = 5.8 +/- 1.6 x 10(5) M-1
      s-1. The L-stereoisomer of methionine competitively inhibited the enzyme reaction
      with a Ki of 3.4 +/- 0.2 mM. It is suggested that acylase I might not only be
      involved in the catabolism of intracellular N-acylated protein but also be
      responsible for the biological utilization of N-acylated food proteins.

PMID- 9258436
TI  - Characterization of an amino-terminal fragment of the bacteriophage T4 uvsY
      recombination protein.
AB  - The uvsY protein plays essential roles in homologous genetic recombination
      processes in the bacteriophage T4. In vitro, uvsY promotes the formation of
      presynaptic filaments containing stoichiometric amounts of the T4 uvsX
      recombinase bound to single-stranded DNA. uvsY protein has intrinsic binding
      activities towards ssDNA, uvsX, and gp32, the T4-encoded SSB, however, it has not
      been directly determined which of these activities are essential for uvsY's role
      in presynapsis. We have therefore sought to generate altered forms of uvsY
      deficient in uvsX- and/or gp32-binding, in order to assess whether these specific
      protein-protein interactions are essential for uvsY recombination functions.
      Limited chymotrypsinolysis of the 16 kDa uvsY protein generates two major
      fragments: an 11.5 kDa fragment containing the N-terminus of uvsY, and a 4.5 kDa
      C-terminal fragment. We have expressed and purified the large fragment as a
      fusion protein containing the N-terminal 101 amino acids of uvsY. We show that
      this truncated uvsY species, which we call uvsYNT, retains ssDNA-binding
      activity, but is devoid of both uvsX- and gp32-binding activities. Like native
      uvsY, uvsYNT stimulates the ssDNA-dependent ATPase activity of the uvsX protein,
      however, the synergistic effects observed between uvsY, uvsX, and gp32 are not
      observed with uvsYNT. In addition, uvsYNT weakly stimulates uvsX-catalyzed DNA
      strand exchange reactions. The latter result is surprising since it suggests that
      specific interactions with uvsX and/or gp32 are not absolutely essential for uvsY
      recombination functions. Taken together, the data are consistent with a model in
      which uvsY-ssDNA interactions alone are capable of promoting the assembly of
      functional uvsX-ssDNA complexes, while uvsY-protein interactions stabilize uvsX
      ssDNA complexes.

PMID- 9258437
TI  - Cloning and overexpression of polypeptide release factor 1 of Thermus
      thermophilus.
AB  - A prfA gene encoding polypeptide release factor RF1 was cloned from Thermus
      thermophilus. T thermophilus RF1 shares 68% homology with Escherichia coli RF1,
      and its overproduction reduced readthrough translation of UAG, not of UGA, in the
      lacZ gene. Rapid purification of T thermophilus RF1 was achieved by T7-RNA
      polymerase driven overexpression of T thermophilus RF1 protein with a C-terminal
      histidine tag.

PMID- 9258438
TI  - Intron-dependent enzymatic formation of modified nucleosides in eukaryotic tRNAs:
      a review.
AB  - In eukaryotic cells, especially in yeast, several genes encoding tRNAs contain
      introns. These are removed from pre-tRNAs during the maturation process by a tRNA
      specific splicing machinery that is located within the nucleus at the nuclear
      envelope. Before and after the intron removal, several nucleoside modifications
      are added in a stepwise manner, but most of them are introduced prior to intron
      removal. Some of these early nucleoside modifications are catalyzed by intron
      dependent enzymes while most of the others are catalyzed in an intron-independent
      manner. In the present paper, we review all known cases where the nucleoside
      modifications were shown to depend strictly on the presence of an intron. These
      are pseudouridines at anticodon positions 34, 35 and 36 and 5-methylcytosine at
      position 34 of several eukaryotic tRNAs. One common property of the corresponding
      intron-dependent modifying enzymes is that their activities are essentially
      dependent on the local specific architecture of the pre-tRNA molecule that
      comprises the anticodon stem and loop prolonged by the intron domain. Thus
      introns clearly serve as internal (cis-type) RNAs that guide nucleoside
      modifications by providing transient target sites in tRNA for selected nuclear
      modifying enzymes. This situation may be similar to the recently discovered
      (trans-type) snoRNA-guided process of ribose methylations of ribosomal RNAs
      within the nucleolus of eukaryotic cells.

PMID- 9258439
TI  - Heterologous expression in Escherichia coli of the gene encoding an archaeal
      thermoacidophilic elongation factor 2. Properties of the recombinant protein.
AB  - The gene encoding the elongation factor 2 from the hyperthermophilic archaeon
      Sulfolobus solfataricus (SsEF-2) was expressed in Escherichia coli using the pT7
      7 expression vector. The synthesis of the heterologous product did not increase
      upon addition of isopropyl-beta-thiogalactopyranoside. The amount of purified
      intact recombinant SsEF-2 (SsEF-2rec) was about 3 mg from 60 g of transformed wet
      cells. Recombinant and naturally occurring SsEF-2 showed identical
      electrophoretic mobility, immunological properties and the N-terminal amino acid
      sequence; both were lacking the initial methionine. Differently from SsEF-2, SsEF
      2rec did not undergo post-translational modification of His603 into diphthamide,
      as indicated by its inability to be ADP-ribosylated. SsEF-2rec appeared
      indistinguishable from SsEF-2 in the fulfillment of its biological functions; in
      fact, it was fully capable to support poly(Phe) synthesis, to bind GDP and to
      display either the intrinsic or the ribosome-dependent GTPase. Finally, SsEF-2rec
      was endowed with the same heat stability as SsEF-2. Altogether these findings
      proved that SsEF-2rec was functionally active as SsEF-2. The used expression
      system could allow to produce mutated forms of SsEF-2 obtained by mutagenesis of
      the corresponding gene.

PMID- 9258441
TI  - Interaction of a novel fluorescent analog of interferon-gamma with transformed
      cells.
AB  - A fluorescent analog of human recombinant interferon-gamma (IFN-gamma) was
      prepared for the first time. The recovered pyrene-labeled IFN-gamma (py-IFN
      gamma), with an estimated seven pyrene molecules per IFN-gamma, retained over
      half of its original biological activity. Binding of py-IFN-gamma to human amnion
      WISH cells showed appreciable enhancement in fluorescence polarization from 0.055
      to 0.215 and in fluorescence lifetime from 56 to 80 ns. The ratio of the vibronic
      peaks did not change, indicating that the pyrene molecules remained in water
      environment even after binding. Py-IFN-gamma provides a novel tool for unraveling
      the mechanism of the initial interaction between this antiproliferative
      lymphokine and its target, cancer cell membrane receptors. Its fluorescence could
      provide the means to follow receptor recycling when it occurs.

PMID- 9258440
TI  - Synthesis and characterization of the new cytostatic complex cis
      diammineplatinum(II)-chlorocholylglycinate.
AB  - Owing to the high efficiency of hepatocytes to take up bile acids, these
      endogenous compounds or their analogues can be considered as potential shuttles
      for delivering drugs to the liver. With the aim of using this strategy to target
      platinum(II)-related cytostatic drugs toward the hepatobiliary system, a
      cholylglycinate (CG) derivative of cis-diammineplatinum(II) has been synthesized
      by treatment of cis-diammineplatinum(II) dichloride with sodium cholylglycinate.
      The complex, named Bamet-R2, was characterized by spectroscopy and elemental
      analysis. Results obtained in these studies together with conductivity
      measurements, which pointed to nonelectrolyte behavior, allowed the structure of
      the complex to be identified as C26H48N3O6ClPt. The compound was found to be
      soluble (up to 3 mM) in water and was highly soluble (more than 10 mM) in
      ethanol, methanol, and dimethyl sulfoxide. Its stability in solution was
      monitored by HPLC analysis. In deionized water, the compound remains > 90% pure
      in solution for up to 7 days and > 80% for up to 28 days. However, in 150 mM NaCl
      it remains as > 90% pure compound in solution for only 1 day. By contrast with
      the parent compound CG, Bamet-R2 was found to significantly inhibit the growth of
      rat hepatocytes in primary culture and L1210 murine leukemia cells, although in a
      less marked way than that observed for cisplatin. The cytostatic effect of Bamet
      R2 was particularly strong against human colon adenocarcinoma LS174T cells. The
      results point to the potential usefulness of Bamet-R2 in the antitumoral therapy
      of enterohepatic-derived neoplasias.

PMID- 9258442
TI  - Immobilization of reducing sugars as toxin binding agents.
AB  - A simple and economical procedure for the attachment of reducing sugars to
      aminated solid supports has been developed. Reaction of the amino groups on the
      solid support with p-nitrophenyl chloroformate, followed by 1,6-hexanediamine,
      yields a chain-extended amine to which reducing sugars can be attached while
      remaining accessible to macromolecules. Immobilization of the reducing sugars
      involves a simple incubation followed by trapping of the resulting glycosylamine
      with acetic anhydride and recovery of the unreacted sugar by filtration. This
      technique was used to immobilize lactose and sialyllactose onto silylaminated
      Chromosorb P, producing solid supports that effectively neutralized the activity
      of cholera toxin from Vibrio cholerae and heat-labile enterotoxin of
      enterotoxigenic Escherichia coli. The general applicability of such solid
      supports for toxin neutralization was further demonstrated by immobilization of
      the enzymatically synthesized alpha Gal(1-3) beta Gal(1-4)Glc trisaccharide,
      which produced a support that efficiently neutralized toxin A of Clostridium
      difficile. The results from this study suggest that these solid supports have the
      potential to serve as inexpensive therapeutics for bacterial toxin-mediated
      diarrheal diseases.

PMID- 9258443
TI  - Nicotinic acetylcholine receptor labeled with a tritiated, photoactivatable
      agonist: a new tool for investigating the functional, activated state.
AB  - Upon agonist activation, the nicotinic acetylcholine receptor undergoes
      allosteric transitions leading to channel opening and sodium ion influx. The
      molecular structure of the agonist binding site has been mapped previously by
      photoaffinity labeling, but most photosensitive probes used for this purpose
      interact only with closed receptor states (resting or desensitized). We have
      synthesized two novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives
      as cholinergic agonist candidates, with the objective of identifying structural
      changes at the acetylcholine binding site associated with receptor activation.
      One of these ligands, 9b, is a functional agonist at muscle acetylcholine
      receptors in human TE 671 cells. In photolabeling experiments with 9b, up to 35%
      inactivation of agonist binding sites was observed at Torpedo acetylcholine
      receptors. Tritiated 9b was synthesized, and photolabeling was found to occur
      mainly on the alpha-subunit in a partially protectable manner. This novel
      radiolabeled photoprobe appears to be suitable for future investigation of the
      molecular dynamics of allosteric transitions occurring at the active
      acetylcholine receptor binding site.

PMID- 9258445
TI  - Cyclopentadienyl iron dicarbonyl (eta 1-N-phthalimidato) complexes containing an
      isothiocyanate function: synthesis and application to protein side-chain
      selective labeling.
AB  - The two first transition metal carbonyl isothiocyanates were prepared in high
      yield within two steps from photolysis of CpFe(CO)2I and 3- or 4-aminophthalimide
      in the presence of diisopropylamine followed by reaction with
      thiophosgene/triethylamine. Their reaction with a model amino acid, i.e. beta
      alanine, was performed and led to the expected thioureas. When reacted with
      bovine serum albumin in aqueous medium, conjugates bearing 6-10 iron-carbonyl
      fragments were obtained and characterized by Fourier transform infrared
      spectroscopy, thus demonstrating the usefulness of these reagents for the
      selective and covalent labeling of proteins.

PMID- 9258444
TI  - Synthesis and characterization of a peptide nucleic acid conjugated to a D
      peptide analog of insulin-like growth factor 1 for increased cellular uptake.
AB  - DNA therapeutics show great potential for gene-specific, nontoxic therapy of a
      wide variety of diseases. The deoxyribose phosphate backbone of DNA has been
      modified in a number of ways to improve nuclease stability and cell membrane
      permeability. Recently, a new DNA derivative with an amide backbone instead of a
      deoxyribose phosphate backbone, peptide nucleic acid (PNA), has shown tremendous
      potential as an antisense agent. Although PNAs hybridize very strongly and
      specifically to RNA and DNA, they are taken up by cells very poorly, limiting
      their potential as nucleic acid binding agents. To improve cellular uptake of a
      PNA sequence, it was conjugated to a D-amino acid analog of insulin-like growth
      factor 1 (IGF1), which binds selectively to the cell surface receptor for insulin
      like growth factor 1 (IGF1R). The IGF1 D-peptide analog was assembled on (4
      methylbenzhydryl)amine resin, and then the PNA was extended as a continuation of
      the peptide. The conjugate and control sequences were radiolabeled with 14C or
      fluorescently labeled with fluorescein isothiocyanate. Cellular uptake of the PNA
      peptide conjugate, a control with two alanines in the peptide, and a control PNA
      without the peptide segment were studied in murine BALB/c 3T3 cells, which
      express low levels of murine IGF1R, in p6 cells, which are BALB/c 3T3 cells which
      overexpress a transfected human IGF1R gene, and in human Jurkat cells, which do
      not express IGF1R, as a negative control. The specific PNA-peptide conjugate
      displayed much higher uptake than the control PNA, but only in cells expressing
      IGF1R. This approach may allow cell-specific and tissue-specific application of
      PNAs as gene-regulating agents in vivo.

PMID- 9258446
TI  - Practical method for the multigram separation of the 5- and 6-isomers of
      carboxyfluorescein.
AB  - An efficient preparative method for separating 5- and 6-carboxyfluorescein is
      presented. 6-Carboxyfluorescein dipivalate is isolated as its diisopropylamine
      salt, which can be converted to the free acid or used directly in coupling
      reactions. The 5-isomer is isolated from the acidified mother liquor.
      Isomerically pure carboxyfluoresceins are prepared by hydrolysis of the
      corresponding dipivalates.

PMID- 9258447
TI  - Sonolysis promotes indirect Co-C bond cleavage of alkylcob(III)alamin
      bioconjugates.
AB  - Sonolysis of aqueous solutions produces H. and HO. that lead to Co-C bond
      cleavage in methylcob-(III)alamin (CH3-CblIII) and 2-[4-[4'-[bis(2
      chloroethyl)amino]phenyl]butyroxy]ethylcob (III)alamin (Chl-HE-CblIII). Under
      anaerobic conditions, H. reduces CH3-CblIII to the unstable 19 e-CH3-CblII that
      dissociates to the alkane and CblII. Under aerobic conditions, O2 scavenges H.
      and Co-C bond cleavage occurs via a HO.-mediated process along with modification
      of the corrin ring by HO.. When H. and HO. are scavenged, there is no evidence of
      Co-C bond cleavage. This suggests no direct sonolysis of the Co-C bond occurs, in
      spite of the fact that the Co-C bond is 80 kcal/mol weaker than the H-OH bond. A
      bioconjugate of cob(III)alamin and the alkylating agent chlorambucil has been
      synthesized to give 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob(I
      II)alamin. The chlorambucil-cobalamin complex also undergoes Co-C bond cleavage
      in a manner similar to that of methylcob-(III)alamin. Sonorelease of an active
      alkylating agent from the bioconjugate may provide a new method for the selective
      release of anticancer drugs and thus potentially reduce systemic toxicity.

PMID- 9258448
TI  - Fluorescein-conjugated lysine monomers for solid phase synthesis of fluorescent
      peptides and PNA oligomers.
AB  - Fluorescein ethyl ester, I, was used to prepare the fluorescent mixed ester/ether
      6-O-(carboxymethyl)-fluorescein ethyl ester, III. Conjugation of III to the
      epsilon-amino group of alpha-N-Boc-L-lysine, via the N-hydroxysuccinimde ester,
      IV, gave the Boc-protected fluorescein-conjugated lysine monomer V. Removal of
      the Boc group, followed by reaction with Fmoc chloride, gave the Fmoc-protected
      monomer, VI (Figure 1). These Boc- and Fmoc-protected fluorescein-conjugated
      lysines were readily incorporated into peptides and PNA oligomers during solid
      phase synthesis to give fluorescent products. Mass spectroscopy and UV studies
      showed that the fluorophore remains unchanged during solid phase synthesis. In
      contrast to fluorescein, the photophysical properties of these derivatives are pH
      independent from pH 3 to 8, with a molar absorption coefficient, epsilon max 456,
      of 2.9 x 10(4) M-1 cm-1 and fluorescence quantum yield, phi f, of 0.18.

PMID- 9258449
TI  - Construction, expression, and activities of L49-sFv-beta-lactamase, a single
      chain antibody fusion protein for anticancer prodrug activation.
AB  - The L49 (IgG1) monoclonal antibody binds to p97 (melanotransferrin), a tumor
      selective antigen that is expressed on human melanomas and carcinomas. A
      recombinant fusion protein, L49-sFv-bL, that contains the antibody binding
      regions of L49 fused to the Enterobacter cloacae r2-1 beta-lactamase (bL) was
      constructed, expressed, and purified to homogeneity in an Escherichia coli
      soluble expression system. The variable regions of L49 were cloned by reverse
      transcription-polymerase chain reaction from L49 hybridoma mRNA using signal
      sequence and constant region primers. Construction of the gene encoding L49-sFv
      bL was accomplished by hybridization insertion of VH, VL, and sFv linker
      sequences onto a pET phagemid template containing the bL gene fused to the pelB
      leader sequence. Optimal soluble expression of L49-sFv-bL in E. coli was found to
      take place at 23 degrees C with 50 microM isopropyl beta-D-thiogalactopyranoside
      induction and the use of the nonionic detergent Nonidet P-40 for isolation from
      the bacteria. Construction and expression of a soluble form of the p97 antigen in
      Chinese hamster ovary cells allowed affinity-based methods for analysis and
      purification of the fusion protein. Surface plasmon resonance, fluorescent
      activated cell sorting, and Michaelis-Menten kinetic analyses showed that L49-sFv
      bL retained the antigen binding capability of monovalent L49 as well as the
      enzymatic activity of bL. In vitro experiments demonstrated that L49-sFv-bL bound
      to 3677 melanoma cells expressing the p97 antigen and effected the activation of
      7-(4-carboxybutanamido)cephalosporin mustard (CCM), a cephalosporin nitrogen
      mustard prodrug. On the basis of these results, L49-sFv-bL was injected into nude
      mice with subcutaneous 3677 tumors, and localization was determined by measuring
      bL activity. Tumor to blood conjugate ratios of 13 and 150 were obtained 4 and 48
      h post conjugate administration, respectively, and the tumor to liver, spleen,
      and kidney ratios were even higher. A chemically produced L49-Fab'-bL conjugate
      yielded a much lower tumor to blood ratio (5.6 at 72 h post administration) than
      L49-sFv-bL. Therapy experiments established that well-tolerated doses of L49-sFv
      bL/CCM combinations resulted in cures of 3677 tumors in nude mice. The favorable
      pharmacokinetic properties of L49-sFv-bL allowed prodrug treatment to be
      initiated 12 h after the conjugate was administered. Thus, L49-sFv-bL appears to
      have promising characteristics for site-selective anticancer prodrug activation.

PMID- 9258450
TI  - Enhanced transepithelial transport of peptides by conjugation to cholic acid.
AB  - The potential of the intestinal bile acid transporter to serve as a shuttle for
      small peptide molecules was investigated. Eleven peptides with a 2-6 amino acid
      backbone were conjugated to the 24-position of 3 alpha, 7 alpha, 12 alpha
      trihydroxy-5 beta-cholan-24-oic acid (cholic acid) via an amide bond using an
      automated peptide synthesizer. In a human intestinal cell line (CaCo-2), cholic
      acid-peptide conjugates were able to inhibit the transepithelial transport of
      [3H]taurocholic acid, a natural substrate for the bile acid carrier, at a 100:1
      conjugate/substrate ratio. Affinity for the carrier decreased significantly when
      the conjugate in the 24-position increased from 1 to 2 amino acids. Further
      increase in the amino acid chain length caused only minor decrease in affinity. A
      tetrapeptide-bile acid conjugate, [3H]-ChEAAA (Ch = cholic acid), was transported
      by the bile acid transporter, showing markedly higher apical (AP)-to-basolateral
      (BL) compared to BL-to-AP transport and inhibition by a 100-fold excess
      taurocholic acid. Another conjugate with 6 amino acids (ChEASASA) was transported
      by a passive diffusion pathway but still showed higher transport rates than the
      passive permeability marker mannitol, suggesting the possibility that the cholic
      acid moiety aids the passive membrane transfer of peptide molecules by increasing
      its lipophilicity. Metabolism of bile acid-peptide conjugates in CaCo-2 cells was
      3% over 3 h. In conclusion, these studies show that the coupling of peptides to
      the 24-position of the sterol nucleus in cholic acid results in a combination of
      decreased metabolism and increased intestinal absorption, either by a carrier
      mediated pathway or by accelerated passive diffusion.

PMID- 9258451
TI  - Bivalent hapten-bearing peptides designed for iodine-131 pretargeted
      radioimmunotherapy.
AB  - Pretargeting with bispecific antibodies has been used successfully for tumor
      detection and is now considered for radioimmunotherapy. The advantages of
      bivalent haptens have been demonstrated in this context. A series of bivalent
      molecules allowing efficient labeling with radioactive iodine has been designed
      for use with this new technology. They were based on the histamine-hemisuccinate
      hapten and prepared by solid phase peptide synthesis. Simultaneous binding of two
      antibody molecules to one bivalent hapten was possible with low steric hindrance
      when the two hapten groups were attached to the lateral chains of lysine residues
      separated by a single amino acid. Bispecific antibodies to the hapten and to
      carcinoembryonic antigen were shown to mediate specific binding of the haptens to
      tumor cells in vitro. These experiments demonstrated that the bivalent hapten
      AG3.0, with a lysyl-D-tyrosyl-lysine connecting chain, possessed the best binding
      properties. This peptide was used to target iodine-125 to human colon cancer
      xenografts in nude mice. High tumor uptake and tumor to normal tissue ratios were
      observed. This peptide thus appears as a good candidate for further development.
      Asymmetric bivalent haptens, with one histamine-hemisuccinate and one
      diethylenetriaminepentaacetic acid group, have also been prepared and shown to be
      capable of binding simultaneously two specific antibody molecules. These peptides
      should be useful to target radioiodine to cells characterized by the expression
      of two different antigenic markers.

PMID- 9258452
TI  - Properties of and oxygen binding by albumin-tetraphenylporphyrinatoiron(II)
      derivative complexes.
AB  - A hydrophobic tetraphenylporphyrinatoiron(II) derivative bearing a covalently
      bound axial imidazole [Fe(II)P] was efficiently and noncovalently bound into
      human serum albumin (HSA) up to an average of eight Fe(II)P molecules per HSA
      molecule. The aqueous solutions of the HSA-Fe(II)P complex provided a reversible
      and relatively stable oxygen adduct under physiological conditions (pH 7.4 and 37
      degrees C). The half-life of the oxygen adduct (tau 1/2) was 1 h at 37 degrees C
      in an air atmosphere. With Fe(II)-TpivPP (the so-called "picket-fence heme")
      having no axial base, an oxygenated HSA-Fe(II)TpivPP complex was obtained using a
      20-fold molar excess of 1,2-dimethylimidazole, but the tau 1/2 was very short
      (ca. 10 min at 37 degrees C). The oxygen affinity [P 1/2(O2)] and oxygen
      transporting efficiency (OTE) of HSA-Fe(II)P at 37 degrees C were 30 Torr and
      22%, respectively. Furthermore, the oxygen-binding and dissociation rate
      constants (kon and koff) are extremely high in comparison with those of
      hemoglobin. The HSA molecule binding eight Fe(II)P molecules can transport about
      3.4 mL/dL of oxygen under physiological conditions, corresponding to about 60% of
      the oxygen transporting amount of human blood.

PMID- 9258453
TI  - Methemoglobin formation in hemoglobin vesicles and reduction by encapsulated
      thiols.
AB  - The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified
      concentrated Hb in a phospholipid vesicle. In order to suppress metHb formation
      or autoxidation, for the long-term maintenance of the oxygen transporting
      capability, a series of thiols (cysteine, Cys; glutathione, GSH; homocysteine,
      Hcy; and acetylcysteine, Acy) were studied as reductants of metHb. Hcy and GSH
      showed a good suppressive effect on metHb formation, while Cys adversely
      accelerates the metHb formation at a rate twice that of the Hb solution without
      any reductants and Acy showed no change. The significant suppression by the
      coaddition of superoxide dismutase (SOD) and catalase to Cys indicated that Cys
      was easily oxidized by oxygen and simultaneously generates a large amount of
      active oxygens. The effective suppression of metHb formation by SOD and catalase
      was not observed for HbV containing no reductants, indicating that the generation
      of active oxygens from Hb itself is not significant. The coencapsulation of Hcy
      with Hb resulted in a low rate of metHb formation in HbV (initial rate, 1%/h) in
      vitro at an oxygen partial pressure (Po2) of 142 Torr. The rate increased with
      decreasing Po2, showed a maximum (2.2%/h) around Po2 = 23 Torr, and then
      decreased to 0%/h at 0 Torr. From these results, it is suggested that the fast
      metHb formation rate in the blood circulation of Wistar rats injected with 20 vol
      % of the HbV solution would be mainly caused by the exposure of HbV to the low
      Po2.

PMID- 9258455
TI  - Biotin-fluorophore conjugates with poly(ethylene glycol) spacers retain intense
      fluorescence after binding to avidin and streptavidin.
AB  - Conventional biotin-fluorophore conjugates with approximately 14 atom spacers
      lose most of their fluorescence when binding to avidin or streptavidin, as is
      demonstrated in the present study. This explains the unusual fact that only
      biotinylated marker enzymes, but not fluorescent biotins, are regularly used in
      bioanalytic assays. Novel biotin-spacer-fluorophore conjugates are presented that
      retain intense fluorescence when binding to avidin or streptavidin. Preservation
      of fluorescence depends upon the use of poly(ethylene glycol) (PEG) spacers,
      which are shown not to interfere with biotin function. The observed absence of
      nonspecific interactions may also be attributed to the PEG chain. These novel
      fluorescent biotins are expected to be excellent new tools in fluorescence
      microscopy and related techniques.

PMID- 9258454
TI  - Basic studies on heterobifunctional biotin-PEG conjugates with a 3-(4
      pyridyldithio)propionyl marker on the second terminus.
AB  - Heterobifunctional poly(ethylene glycol) (PEG) derivatives with a biotin terminus
      have been synthesized and characterized with respect to avidin binding.
      Unambiguous measurement of biotinyl and pyridyldithiopropionyl end groups was
      established by selecting suitable assays and introducing necessary modifications.
      Functional studies on the binding of biotin-PEG conjugates to avidin tetramers
      revealed much similarity to known biotin-spacer-peptide conjugates with 7-27 atom
      spacers: dissociation kinetics of the initially formed 4:1 complexes were
      multiexponential, the complex with 2 ligands per avidin dissociating rather
      slowly with half-times of approximately 2 days at 25 degrees C. The observed
      stability of 3:1 and 2:1 complexes with avidin is particularly significant since
      it allows exploitation of the additional advantages of PEG spacers, i.e. reduced
      steric strain in biotin-avidin-biotin bridges, reduced nonspecific adsorption of
      biotinylated probes and markers, and, especially, uncomparable fluorescence
      intensities of biotin-PEG-fluorophore conjugates as is demonstrated in the
      accompanying study (second of three papers in this issue).

PMID- 9258456
TI  - Biotin-pyrene conjugates with poly(ethylene glycol) spacers are convenient
      fluorescent probes for avidin and streptavidin.
AB  - Conventional biotin-fluorophore conjugates with approximately 14 atom spacers are
      strongly quenched when bound to avidin or streptavidin, whereas fluorescence
      becomes insensitive to receptor binding if typical fluorophores are linked to
      biotin via poly(ethylene glycol) (PEG) chains (Gruber et al., see the second of
      three papers in this issue). In the present study the antagonism between PEG-PEG
      repulsion and fluorophore interaction was examined more closely, using biotin-PEG
      pyrene conjugates as model compounds. The antagonistic tendencies between
      hydrophilic PEG chains and hydrophobic pyrene labels were about balanced in the
      PEG1900 derivative since quenching was approximately 50% in 4:1 complexes with
      avidin or streptavidin. In contrast, strong quenching and concomitant excimer
      fluorescence was seen with the biotin-PEG800-pyrene conjugate, providing for a
      new fluorescence assay to accurately measure avidin and streptavidin
      concentrations at > or = 40 and > or = 10 nM, respectively. Association/
      dissociation kinetics were analyzed from pyrene fluorescence changes, and
      dissociation constants were deduced. About 3-fold affinities were observed for
      streptavidin as compared to avidin, and little influence of PEG chain length was
      seen. All affinities were increased by a factor of approximately 3 when biotin
      PEG-tetramethylrhodamine conjugates were used. The observed effect of fluorophore
      variation upon biotin binding is unexpectedly small; thus, the
      kinetic/thermodynamic data appear to be representative for biotin-PEG conjugates
      in general.

PMID- 9258457
TI  - Neoglycophospholipids with alkyl spacers: synthesis via an improved reductive
      amination and monolayer properties.
AB  - An efficient synthesis of neoglycophospholipids with variable length alkyl spacer
      chains is described. Neoglycophospholipids tethered by alkyl chains of 3, 5, 7,
      10, and 16 methylene units were synthesized in good overall yields in four steps.
      The key intermediates, omega-oxoalkyl glycopyranosides, were synthesized in two
      steps by glycosidation of chloro (or ethylthio) glycosides with a diol followed
      by oxidation of the remaining hydroxy group to an aldehyde functionality.
      Conjugation of the omega-glycoalkyl aldehyde with
      distearoylphosphatidylethanolamine via an improved reductive amination procedure
      significantly enhanced efficiency and yields with respect to those from
      traditional procedures. The amphiphilic properties of the neoglycophospholipids
      were characterized at the air-water interface. While the carbohydrate head group
      had relatively little effect, the length of the alkyl spacer profoundly
      influenced surface area-pressure isotherms.

PMID- 9258458
TI  - Biotin reagents for antibody pretargeting. Synthesis, radioiodination, and in
      vitro evaluation of water soluble, biotinidase resistant biotin derivatives.
AB  - As part of our development of antibody pretargeting for cancer therapy, an
      investigation has been conducted to examine the stability of water solubilized,
      radioiodinated biotin derivatives toward biotinidase degradation in mouse and
      human serum. Eight new biotin derivatives were synthesized to conduct the study.
      The biotin derivatives synthesized contained (1) the biotin moiety, (2) a water
      solubilizing linker moiety, (3) p-iodobenzoate or p-tri-n-butylstannylbenzoate
      moieties, and (4) in some of the compounds, N-methyl or alpha-methyl containing
      moieties were added to block biotinidase activity. The linker moiety, 4,7,10
      trioxa-1,13-tridecanediamine, 5, was included in the biotin derivatives to
      improve their water solubility, and it also functioned as a 17 A spacer between
      the biotin and the benzoyl moieties. Four of the new biotin derivatives (12, 14,
      22, and 23) contained a p-tri-n-butylstannylbenzoyl moiety as precursors which
      could be radioiodinated in the last synthetic step. The other four biotin
      derivatives (13, 15, 24, and 25) contained p-iodobenzoyl moieties and were used
      as HPLC reference standards. Initial studies involved radioiodination of 12 to
      yield [125I]13. Radioiodinated 13, which did not contain a moiety for blocking
      biotinidase activity, was found to be rapidly degraded in both mouse and human
      serum at 37 degrees C. Derivatives which were designed to be stable to
      biotinidase incorporated N-methyl and alpha-methyl moieties adjacent to the
      biotin carboxylate group. In one set of biotin derivatives (14 and 15), the N
      methyl moiety was obtained by incorporating N,N-dimethyl-4,7,10-trioxa-1,13
      tridecanediamine, 9, as a linker in the place of 5. In the second set of biotin
      derivatives (22 and 24), the N-methyl moiety was introduced by incorporating a
      sarcosine (N-methylglycine) moiety between biotin and 5. The radioiodinated N
      methyl containing biotin derivatives [125I]15 and [125I]24 were found to be very
      stable to biotinidase degradation. An alpha-methyl group was obtained in a pair
      of biotin derivatives (23 and 25) by incorporating a 3-aminobutyric acid moiety
      between biotin and 5. The radioiodinated alpha-methyl containing derivative,
      [125I]25, was found to have an intermediate stability with regards to biotinidase
      degradation.

PMID- 9258460
TI  - Development of a streptavidin-anti-carcinoembryonic antigen antibody,
      radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal
      cancer. Studies in a human colon cancer xenograft model.
AB  - Pretargeting methodologies can produce high tumor:blood ratios, but their role in
      cancer radioimmunotherapy (RAIT) is uncertain. A pretargeting method was
      developed using a streptavidin (StAv) conjugate of MN-14 IgG, an anti
      carcinoembryonic antigen (CEA) murine monoclonal antibody (mab) as the primary
      targeting agent, an anti-idiotype antibody (WI2 IgG) as a clearing agent, and
      DTPA- or DOTA-conjugated biotin as the radiolabeled targeting agent. A variety of
      reagents and conditions were examined to optimize this method. At 3 h, 111In-DTPA
      peptide-biotin tumor uptake was 3.9 +/- 0.8% per gram and tumor:blood ratios were
      > 11:1. By 24 h, this ratio was 178:1, but tumor accretion declined in accordance
      with the gradual loss of StAv-MN-14 from the tumor. Tissue retention was highest
      in the liver and kidneys, but their tumor:organ ratios were > 2:1. Dosimetry
      predicted that radiolabeled MN-14 alone would deliver higher tumor doses than
      this pretargeting method. Increasing the specific activity and using DOTA-biotin
      in place of DTPA increased tumor uptake nearly 2-fold, but analysis of StAv-MN
      14's biotin-binding capacity indicated over 90% of the initial biotin-binding
      sites were blocked within 24 h. Animals fed a biotin-deficient diet had 2-fold
      higher 111In-DOTA-biotin uptake in the tumor, but higher uptake also was observed
      in all normal tissues. Although exceptionally adept at achieving high tumor:blood
      ratios rapidly, the tumor uptake of radiolabeled biotin with this pretargeting
      method is significantly (p < 0.0001) lower than that with a radiolabeled
      antibody. Endogenous biotin and enhanced liver and kidney uptake may limit the
      application of this method to RAIT, especially when evaluating the method in
      animals, but with strategies to overcome these limitations, this pretargeting
      method could be an effective therapeutic alternative.

PMID- 9258461
TI  - Polymeric conjugates of Gd(3+)-diethylenetriaminepentaacetic acid and dextran. 1.
      Synthesis, characterization, and paramagnetic properties.
AB  - Macromolecular conjugates of dextran and diethylenetriaminepentaacetic acid
      (DTPA), aimed to complex gadolinium, were synthesized to obtain contrast agents
      for nuclear magnetic resonance imaging with good paramagnetic properties and long
      intravascular persistence. These conjugates were prepared from dextran 40 (Mn =
      38 kg/mol and Mw = 43 kg/mol), which was first carboxymethylated. Then amines
      were introduced by reacting ethylenediamine with dextran carboxylic acid groups
      in the presence of 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline. DTPA was
      then covalently linked to aminated dextran by using three different coupling
      procedures (DTPA bisanhydride, dicyclohexylcarbodiimide/N-hydroxysuccinimide, and
      isobutyl chloroformate). The different final products were compared in terms of
      DTPA contents, molecular masses, and sizes, and it was proved that the last
      synthesis step led to a small fraction of cross-linked chains as Mn was between
      128 and 166 kg/mol and Mw between 332 and 371 kg/mol. In spite of this partial
      cross-linking which theoretically decreases the complexation capacity of the
      dextran-linked DTPA molecules, the Gd(3+)-complexed conjugates exhibited
      relaxivities at 20 MHz/mol of gadolinium-2.5 times as great as that of free
      GdDTPA2-.

PMID- 9258459
TI  - Development of a streptavidin-anti-carcinoembryonic antigen antibody,
      radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal
      cancer. Reagent development.
AB  - With pretargeting, radioisotope delivery to tumor is decoupled from the long
      antibody localization process, and this can increase tumor:blood ratios
      dramatically. Several reagents were prepared for each step of a "two-step"
      pretargeting method, and their properties were investigated. For pretargeting
      tumor, streptavidin-monoclonal antibody (StAv-mab) conjugates were prepared by
      cross-linking sulfo-SMCC-derivatized streptavidin to a free thiol (SH) group on
      MN-14 [a high-affinity anti-carcinoembryonic antigen (CEA) mab]. Thiolated mabs
      were generated either by reaction of 2-iminothiolane (2-IT) with mab lysine
      residues or by reduction of mab disulfide bonds with (2-mercaptoethyl)amine
      (MEA). Both procedures gave protein-protein conjugates isolated in relatively low
      yields (20-25%) after preparative size-exclusion (SE) chromatography purification
      with conservative peak collection. Both StAv-MN-14 conjugates retained their
      ability to bind to CEA, to an anti-idiotypic antibody to MN-14 (WI2), and to
      biotin, as demonstrated by SE-HPLC. Two clearing agents, WI2 mab and a biotin
      human serum albumin (biotin-HSA) conjugate, were developed to remove excess
      circulating StAv-MN-14 conjugates in animals. Both clearing proteins were also
      modified with galactose residues, introduced using an activated thioimidate
      derivative, to produce clearing agents which would clear rapidly and clear
      primary mab rapidly. At least 14 galactose residues on WI2 were required to
      reduce blood levels to 5.9 +/- 0.7% ID/g in 1 h. Faster blood clearance (0.7 +/-
      0.2% ID/g) was observed in 1 h using 44 galactose units per WI2. For the delivery
      of radioisotope to tumor, several biotinylated conjugates consisting of biotin, a
      linker, and a chelate were prepared. Conjugates showed good in vitro and in vivo
      stability when D-amino acid peptides were used as linkers, biotin-peptide-DOTA
      indium-111 had a slightly longer blood circulation time (0.09 +/- 0.02% ID/g in 1
      h) than biotin-peptide-DTPA-indium-111 (0.05 +/- 0.03% ID/g in 1 h) in nude mice.
      A longer circulation time with the neutral DOTA complex might allow higher tumor
      uptake.

PMID- 9258462
TI  - 8-(omega-aminoalkyl)theophyllines and their use in preparing fluorescently
      labeled derivatives for applications in immunoassay.
AB  - Reaction of alkane-1, omega-diamines with 6-chloro-1,3-dimethylpyrimidine-2,4
      dione under carefully controlled conditions gives 6-(omega-aminoalkylamino)-1,3
      dimethylpyrimidine-2,4-diones, which can be readily separated from traces of
      products of disubstitution after benzyloxycarbonyl protection. A sequence of
      nitrosation at the pyrimidine 5-position, thermal cyclization, and deprotection
      affords 8-(omega-aminoalkyl) derivatives of theophylline, an important drug in
      the treatment of asthma and related diseases. These 8-(omega
      aminoalkyl)theophyllines can be coupled to fluorescein-5-isothiocyanate and to
      dansyl chloride, giving fluorescent derivatives of theophylline with applications
      in automated immunoassay of the drug in biofluids using the fluorescence
      capillary fill device.

PMID- 9258463
TI  - A longitudinal study of unsaturated iron-binding capacity and lactoferrin in
      unstimulated parotid saliva.
AB  - Availability of iron is one important nutritional parameter for microbial growth
      in saliva. This longitudinal study measured the diurnal and day-to-day variations
      in the total iron (TI), total iron-binding capacity (TIBC), unsaturated iron
      binding capacity (UIBC), and lactoferrin (LF) in unstimulated human parotid
      saliva. Saliva was collected from 15 young male subjects in the morning and
      afternoon hours each day for five consecutive days. The TI and TIBC were
      determined by flameless atomic absorption spectroscopy, and UIBC was determined
      by subtraction of TI from TIBC. The LF was determined by "sandwich" enzyme-linked
      immunosorbent assay (ELISA). One peripheral blood sample of each subject was also
      analyzed for TI, TIBC, and ferritin. The results showed no significant diurnal or
      day-to-day variation of TI, TIBC, UIBC, or LF in saliva for most subjects.
      However, significant between-subject variations were observed for most
      parameters. Variations ranged from subjects with constantly positive UIBC values
      to subjects with constantly negative UIBC values. The relationship between the LF
      values and the TI and TIBC values suggests that other iron-binding protein(s) are
      present in saliva. Also, saliva had significantly lower TIBC values than serum.
      This finding indicated that iron may be easily available in saliva. However,
      further studies are required to determine the relationship between UIBC value of
      saliva and oral and dental diseases, and also to detect the presence of other
      iron-binding proteins in saliva.

PMID- 9258464
TI  - Biochemical composition of benign thyroid cyst fluid.
AB  - Although the availability of thyroid cyst fluid is easy by fine-needle
      aspiration, less is known about the biochemical composition of thyroid cyst
      fluid. The authors have, therefore, determined the biochemical composition of 18
      benign thyroid cyst fluid specimens. They found that the activities of aspartate
      aminotransferase (AST), lactate dehydrogenase (LDH), and the concentrations of
      total protein, total bilirubin, and uric acid were highly increased in thyroid
      cyst fluid specimens when compared with normal human serum specimens. The
      concentrations of glucose, cholesterol, and triglycerides in cyst fluid were
      within normal serum limits. Selenium (Se) concentrations in most cyst fluids were
      low. Moreover, there was no correlation between Se and other biochemical
      parameters. Protein electrophoresis of cyst fluid specimens yielded high
      concentrations of alpha 1 and especially alpha 2 globulin fractions indicating an
      inflammation. The concentrations or activities of biochemical analytes were not
      significantly different in pure and mixed cysts. Those parameters were also not
      significantly different between cyst fluids of different colors. The gross
      appearance of the fluid and the presence of certain biochemical analytes were
      consistent with a hemorrhagic origin of most of the cyst fluid specimens.
      However, some biochemical markers indicate that autolysis or necrosis of thyroid
      tissue may also contribute the composition of thyroid cyst fluid. The reason for
      lower Se concentration in the thyroid cyst fluid may be the lower Se
      concentration in the Turkish population. These results also suggest that the
      fluid color or nature of cyst, e.g., pure or mixed cyst, is not a main
      determinant of biochemical composition of benign thyroid cyst fluid.

PMID- 9258465
TI  - Analysis of trace elements in the hair of volunteers suffering from naso
      pharyngeal cancer.
AB  - This article describes a study where the trace elements (TEs) of four groups of
      volunteers were analyzed. The volunteers were divided into four groups A, B, C,
      and D. Group A was made up of healthy subjects, group B was made up of volunteers
      who had just been diagnosed as having naso-pharyngeal cancer (NPC), group C was
      made up of volunteers who had been diagnosed as having NPC after 3 mo of
      treatment, and group D was made up of volunteers who had been diagnosed as having
      NPC after 6 mo of treatment. In all groups, 11 trace elements in hair were
      analyzed. Our study shows that the concentrations of zinc (Zn), copper (Cu),
      manganese (Mn), and cobalt (Co) in group B are less than that of group A, whereas
      the concentration of titanium (Ti) in group B is higher. Our results also show
      that the difference in the level of TEs between group A and the other groups is
      dramatically decreased as the time of the treatment is increased. This may be a
      reflection of successful treatment.

PMID- 9258466
TI  - High accumulation of elements in the human femoral artery.
AB  - The relative contents (RCs) of elements in the femoral arteries as well as the
      thoracic aorta, coronary, basilar, and radial arteries from 26 subjects within
      the age range between 55 and 92 yr old, were analyzed by inductively coupled
      plasma atomic emission spectrometry. The RCs of calcium and phosphorus in the
      femoral arteries started to increase before the age of 60 yr. The RCs of
      magnesium increased after the age of 70 yr. However, the RCs of sulfur did not
      change significantly within the age range between 55 and 92 yr. With regard to
      localization of the mineral accumulations in the femoral arterial wall, it was
      found that the accumulations of calcium and phosphorus occurred only in the
      tunica media, only in the tunica intima, or in both the tunica media and the
      tunica intima. The manner of accumulation of calcium and phosphorus in the
      femoral arterial wall was different from that in the aortic wall. The average RCs
      of calcium in the 26 specimens were the highest in the femoral artery, followed
      in descending order by the thoracic aorta, coronary, basilar, and radial
      arteries. The average RCs of phosphorus were highest in the thoracic aorta,
      followed by the coronary, femoral, basilar, and radial arteries. It is noted that
      the accumulation of mineral elements never occurred uniformly in all the
      arteries.

PMID- 9258467
TI  - Contents of pollutant and nutrient elements in rice and wheat grown on the
      neighboring fields.
AB  - Because of recent agricultural policy to suppress rice production, a rather rare
      situation occurred in one prefecture in Japan that rice and winter wheat were
      grown in fields neighboring each other, rice being grown from May to October, and
      wheat from November to June of the next year. Grains of such rice and wheat were
      analyzed for cadmium (Cd) and lead (Pb) by atomic absorption spectrometry, and
      eight nutrient minerals by inductively coupled plasma emission spectrometry.
      Concentrations of nutrient minerals were higher in wheat grains than in
      unpolished rice grains (without husk), and similar trends were observed also for
      Cd and Pb. Flour obtained by milling of the wheat grains had significantly less
      Cd and nutrient minerals than the mother grains, and such reduction was also
      observed by treatment of unpolished rice to polished grain. Pb concentration was
      also reduced by the polishing of rice. Pb in wheat flour appeared to be higher
      than that in whole grain. Comparisons between the final edible forms of the two
      cereals showed that K and Cu were higher in polished rice than in wheat flour and
      that such may also be the case for Cd, whereas the reverse was the case for Ca
      and Fe, and possibly for Pb.

PMID- 9258468
TI  - Influence of L-lysine and zinc administration during exposure to lead or lead and
      ethanol in rats.
AB  - Influence of lysine and zinc administration on the lead-sensitive biochemical
      parameters and the accumulation of lead during exposure to lead or lead and
      ethanol was investigated in rats. The lead exposure inhibited blood delta
      aminolevulinic acid dehydratase (ALAD) activity, increased blood zinc
      protoporphyrin (ZPP), urinary delta-aminolevulinic acid (ALA), serum glutamic
      oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), blood
      and tissue lead levels, and decreased blood and hepatic glutathione (GSH)
      contents. Some of these effects were enhanced on coexposure to ethanol. The
      simultaneous administration of lysine and zinc reduced tissue accumulation of
      lead and most of the lead-induced biochemical alterations irrespective of
      exposure to lead alone or lead and ethanol. The depletion of endogenous calcium
      and magnesium owing to lead or ethanol exposure was also prevented by co
      administration of lysine and zinc.

PMID- 9258469
TI  - Cadmium accumulation, zinc status, and mineral bioavailability of growing rats
      fed diets high in zinc with increasing amounts of phytic acid.
AB  - Five groups of individually housed albino rats (n = 7, initial average weight =
      48 g) were fed diets based on egg albumen and cornstarch (basal diet 8.2 g Ca,
      6.0 g P, 0.7 g Mg, 225 mg Zn, 150 mg Fe, 60 mg Mn, 8 mg Cu, and 5 mg Cd) over a 4
      wk period. Group I (control) was fed the basal diet free of phytic acid (PA). In
      groups II, III, IV, and V, cornstarch was replaced by 3.5, 7.0, 10.5, and 14.0 g
      sodium phytate/kg diet, respectively. Daily gain, feed efficiency, Zn status (Zn
      in plasma, femur, testes, liver and kidneys, activity of the plasma alkaline
      phosphatase) and apparent absorption of Zn, Fe, Cu, and Mn remained unchanged by
      the different dietary treatments. PA decreased apparent Mg absorption
      significantly and apparent absorption of Ca in tendency. Increasing the amount of
      phytate caused a corresponding enhancement of amount of the digestible P. Cd
      accumulation in the liver was not significantly altered, and kidney Cd
      accumulation slightly increased owing to PA. In conclusion, it was shown that
      under conditions of high dietary Zn, PA had only little effect on the carryover
      of Cd in growing rats.

PMID- 9258470
TI  - Bioelectrical activity of the central nervous system among populations in a rare
      earth element area.
AB  - Auditory brainstem electric response (ABR) and somatosensory evoked potential
      (SEP) of 21 subjects (41 ears) among villagers in a rare earth element (REE) area
      in Gan County, Jiangxi, China, were studied. No difference in ABR between the
      subjects from the REE area and the control group was noted. However, the
      conduction detected by SEP from the median nerve to the thalamus (P15) was
      shortened (P < 0.05), especially to the first-grade primary somatosensory
      responsive region (S1) (P < 0.01) and the amplitude of S1 decreased (P < 0.05),
      indicating that REE was difficult to accumulate in the brainstem, but it was
      susceptible to cerebral cortex, thus causing sub-clinical damage. This condition
      was confirmed in the animal experiment. It was suggested that the toxicity
      through long-term intake of small doses of REE might not be negligible, and the
      hazard of REE environments should be investigated.

PMID- 9258471
TI  - Catalase activity in erythrocytes from colon and gastric cancer patients.
      Influence of nickel, lead, mercury, and cadmium.
AB  - Catalase (CAT) is an enzyme that is involved in antioxidant defense, cell growth,
      and is possibly associated with tumoral processes. In this paper, the results of
      experiments designed to determine the influence of metallic carcinogens such as
      nickel (Ni), lead (Pb), mercury (Hg), and cadmium (Cd), on CAT activity are
      reported. CAT activity was measured in erythrocytes from three groups: a group of
      colon cancer patients, a group of gastric cancer patients before clinical
      treatment, and a control group of healthy blood donors. Concentrations of this
      enzyme are significantly higher than controls in the colon cancer group, but
      lower in gastric neoplasia. By generating highly reactive oxygenated species, Ni,
      Pb, Hg, and Cd alter catalase activity. Solutions of Ni, Cd, and Pb at 0.2 mM
      concentrations inhibit CAT activity in colon cancer, but increase it in gastric
      neoplasia. Hg activates CAT in colon cancer, and causes a slightly increased
      activity in gastric cancer. No complete deactivation of the enzyme was observed.

PMID- 9258472
TI  - Determination of standard zinc values in the intact tissues of mice by ICP
      spectrometry.
AB  - The most commonly encountered difficulties for the quantitative measurement of
      zinc in biological samples are the limited sample amount, total and effective
      digestion of connective and fatty residues, and low zinc concentrations. These
      problems often lead to the determination of lower zinc values than actually
      present, so that the sample preparation, digestion, and analytical procedure
      deserve careful attention. In this short communication, a new method for
      microwave tissue disintegration is described. The authors have obtained
      consistent and reproducible results with tissue samples of 0.5 g or less.

PMID- 9258474
TI  - Bare-mounted stents: a bare necessity?

PMID- 9258473
TI  - Use of bare-mounted Palmaz-Schatz stents employing the stent saddle technique on
      the delivery balloon: a single center experience.
AB  - The major limitations of the Palmaz-Schatz stent stem from the design of its
      stent delivery system (SDS). The SDS is bulky and has poor trackability in
      lesions with proximal tortuosity and/or vessel calcification. The use of bare
      mounted Palmaz-Schatz stents on low profile balloons represents an alternate
      approach for lesions that are not accessible for stenting with the SDS. Thus we
      evaluated the indications, procedural success rate, and in-hospital complications
      of patients undergoing bare stenting at a single center between 1 October 1995
      through 30 September 1996. A total of 363 coronary interventions were performed
      during this period, including coronary stenting in 194 vessels. In 18 of these
      194 vessels, bare-mounted Palmaz-Schatz stents were used. The indications for
      bare stenting were: inability to deliver the Palmaz-Schatz stent on SDS for
      suboptimal angioplasty results or acute/threatened abrupt closure; use of half
      stents; stenting in vessels < 3.0 mm; intermediate disease in the proximal
      segment that would have precluded optimal visualization of stent placement; and
      use of guides 7 French or smaller. Bare stenting was successful in 15 of the 18
      patients (vessels) in whom it was attempted. There were no deaths, myocardial
      infarctions, stent thrombosis, repeat interventions, or significant bleeding in
      patients with successful bare stent delivery. The stents were successfully
      retrieved in the three patients in whom the stent could not be advanced into the
      target coronary segment. One of these patients had a propagated spiral dissection
      prior to attempts at bare stenting and required emergent bypass surgery. The
      remaining two patients with failed deployment had suboptimal angioplasty results
      but had an uncomplicated hospital course. Thus bare stenting represents an
      alternate percutaneous approach to tackle suboptimal procedural results and/or
      complications in patients who have failed stent deployment with the standard
      sheathed stent delivery system currently available in the United States.

PMID- 9258476
TI  - Half for me ... half for you!

PMID- 9258475
TI  - Coronary stenting with the half (disarticulated) Palmaz-Schatz stent: immediate
      results and six-month follow-up.
AB  - Coronary stenting with the half disarticulated Palmaz-Schatz stent is
      particularly suitable for ostial stenoses, diaphragm stenoses, stenoses distal to
      tortuous segments or coronary bends and localized dissections after balloon
      angioplasty. Nevertheless very few data regarding the half stent exist and follow
      up data are nonexistent. From January of 1994 to December of 1995 a total of 207
      half stents were implanted in 175 patients. Most patients had stable or unstable
      angina and in the majority of cases the stent was implanted due to localized
      dissection or to suboptimal result. The procedural success rate was 98%. After
      stent implantation, 82 patients were treated with acetylsalicylic acid (ASA) and
      oral anticoagulant (group A), whereas 93 were treated with ASA and ticlopidine
      (group B). Seven patients had subacute thrombosis (5, group A; 2, group B), and
      six patients had major bleeding (5, group A; 1, group B). Overall, patients in
      group A had more cardiovascular complications than patients in group B (10, group
      A; 3, group B; p = 0.047). After 6-mo follow-up, 1 patient had died and 27
      patients had symptoms of angina (16%). Thirteen patients underwent a second PTCA
      (7%) and four patients (2%) were referred for coronary artery bypass. In
      conclusion, coronary stenting with half Palmaz-Schatz stent appears to be a safe
      and effective procedure. In selected cases, the half Palmaz-Schatz stent is
      easier to handle than the complete stent, it is associated with a low rate of
      clinical restenosis, and it lowers procedural costs.

PMID- 9258477
TI  - Sheath pulling immediately after PTCA: comparison of two different deployment
      techniques for the hemostatic puncture closure device: a prospective, randomized
      study.
AB  - Sheath pulling immediately after percutaneous transluminal coronary angioplasty
      (PTCA) increases patients' comfort, decreases burden for the medical staff, and
      may reduce hospital costs by shortening the length of stay. Immediate sheath
      pulling in anticoagulated patients with a low risk of bleeding complications is
      feasible using hemostatic devices. For the hemostatic puncture closing device
      (HPCD), published data regarding sheath pulling in patients immediately after
      PTCA is limited. Furthermore, no study addressed the question whether the
      recommended deployment time (DT) of 30 min can be reduced to a few minutes. We,
      therefore, performed a prospective study, randomizing 140 patients to a DT of 5
      and 30 min, respectively. There were no statistical differences in gender, age,
      height, weight, or cardiovascular risk factors between the two groups. Blood
      pressures measured invasively immediately before sheath removal were comparable.
      Activated coagulation time just prior to sheath removal was 227 +/- 52 sec in the
      DT-5 group and 223 +/- 37 sec in the DT-30 group. After deployment, 74% of the DT
      5 patients and 71% of the DT-30 patients showed immediate and complete
      hemostasis. The remaining patients showed only little oozing with complete
      hemostasis at the time of the final device removal. Hematoma size after 24 hr was
      6.2 +/- 4.4 cm2 for DT-5 and 6.8 +/- 8.2 cm2 for DT-30 patients. There was no
      statistical difference between both groups. No severe bleeding or major
      complications were observed in either group. Thus, the use of a collagen system
      with an intra-arterial anchor (HPCD) is effective and safe when sheaths are
      pulled immediately after PTCA. The reduction of deployment time from 30 to 5 min
      is not related to an increased risk of bleeding or other vascular complications;
      patients can be transferred much faster to the ward, therefore reducing the
      burden on the personnel in the catheterization laboratory and increasing
      patients' comfort by allowing them to return to their rooms without a sheath.

PMID- 9258478
TI  - Arrival of femoral closure devices and the demise of brachial angiography and
      interventions.

PMID- 9258480
TI  - A wake-up call to those who dare to close the patent ductus arteriosus:
      cardiologists, surgeons, FDA ... are you listening?

PMID- 9258479
TI  - Percutaneous closure of patent ductus arteriosus using special screwing
      detachable coils.
AB  - Jackson screwing detachable coils, developed for arterial and venous
      embolization, have been successfully employed recently for the percutaneous
      occlusion of patent ductus arteriosus (PDA). Special screwing detachable coils
      were designed for closure of the PDA, and the experience gained by their use is
      described in this report. Occlusion was attempted in 29 patients with a minimal
      ductal diameter of 0.9-4.2 mm. Coils were successfully placed in all 29 patients.
      One coil, which embolized 10 min after detachment, was retrieved. In 26 patients
      (89%), complete closure was achieved. Only 35 coils were placed in 29 patients.
      Residual shunts in three patients are minimal, detectable only on color-flow
      mapping. Screwing detachable coils for closure of PDA are safe and effective for
      occlusion of PDA with a minimal diameter < 4.2 mm. Embolization of the coil is
      very rare. A high closure rate is achieved with a low number of placed coils.

PMID- 9258481
TI  - Pulmonary intravascular ultrasound in infants and children with congenital heart
      disease.
AB  - A three-layered appearance of the pulmonary arterial wall has only been described
      by intravascular ultrasound in adults or autopsy studies of patients with
      pulmonary hypertension. Thus, pulmonary intravascular ultrasound was performed in
      11 patients during heart catheterization to test the hypothesis that distinct
      layers of peripheral pulmonary arteries can be imaged in infants and children
      with congenital heart disease. A 3.5 Fr 30 MHz ultrasound catheter was used to
      image proximal pulmonary arteries with an internal diameter of 3 to 6 mm and
      distal pulmonary arteries with an internal diameter of 1.5 to 2 mm. Three layers
      were identified in the proximal arteries of 10 patients but could not be
      identified in the distal arteries of any patient. There was a significant linear
      correlation between the indexed dimension of the medial echolucent vascular wall
      layer and pulmonary vascular resistance. We conclude that intravascular
      ultrasound can identify vascular changes consistent with medial hypertrophy in
      the branch pulmonary arteries of young patients with corresponding degrees of
      pulmonary hypertension.

PMID- 9258482
TI  - Predictors of arterial thrombosis after diagnostic cardiac catheterization in
      infants and children randomized to two heparin dosages.
AB  - Arterial thrombosis is the most frequent major complication of percutaneous
      arterial catheterization in children. We prospectively studied the effect of
      randomized dosage of heparin, 50 IU/kg-group I and 100 IU/kg-group II, on the
      incidence of arterial thrombosis in 366 children and analysed the various factors
      which may influence the occurrence of this complication. The age of patients
      ranged from 17 d to 11 yr (mean age 39.5 +/- 40.9 mo) and mean weight was 11.2 +/
      7.8 kg (range 3 to 39 kg). The incidence of arterial thrombosis was 9.8% in
      group I and 9.3% in group II (P = NS). There was no statistical difference in
      precatheterization and procedure variables in the two groups and also in the
      group with absent pulse (n = 35) to the group with pulse present post cath (n =
      331). There were 24.9% infants in our study and 14.3% of these had arterial
      thrombosis. The loss of pulse was more often seen with more number of attempts at
      arterial puncture (P < 0.001), absence of back bleed at the end of the procedure
      (P < 0.001), and increased duration of catheterization (P < 0.01). Use of larger
      sheath size in a given weight and body surface area of children increased
      incidence of arterial thrombosis. The administration of heparin 50 IU/kg was
      equally efficacious to heparin 100 IU/kg. Of the patients with arterial
      thrombosis, 23 responded with intravenous heparin and 12 needed streptokinase.
      There was no bleeding or haematoma. Thus our study shows that less attempt for
      arterial puncture, use of smaller sheath size, maintaining shortest procedure
      time and ensuring back bleed minimises incidence of arterial thrombosis post
      catheterization.

PMID- 9258483
TI  - Acute myocardial infarction in a patient during dobutamine stress
      echocardiography.
AB  - We report the case of a patient who developed an acute anteroseptal and inferior
      myocardial infarction during dobutamine stress echocardiography. The proposed
      mechanism for this event is discussed based on results obtained during emergency
      coronary angioplasty and subsequent clinical findings.

PMID- 9258484
TI  - Coronary aneurysm after bailout stent implantation: diagnosis of a false lumen
      with intravascular ultrasound.
AB  - This case report describes the intravascular ultrasound (IVUS) evaluation of a
      coronary artery aneurysm, developed in a stented segment within 6 mo after
      bailout stenting. Analysis of the IVUS images provides in vivo insights in the
      vessel-remodeling process after mechanical injury. The proximal entrance of the
      false lumen could be clearly visualized as well as the relationship between the
      stent struts, neolumen, and vessel wall. The discussion is focused on the options
      for management of such patients.

PMID- 9258485
TI  - Coronary aneurysms after catheter interventions: an exception to "bigger is
      better".

PMID- 9258486
TI  - Short-term angiographic and long-term clinical follow-up of a patient with a
      malexpanded vein graft stent.
AB  - Optimal stent expansion is considered imperative today in order to prevent
      subacute stent thrombosis and allows us to minimize antithrombotic therapy. The
      short-term angiographic and long-term clinical follow-up of a patient with a
      suboptimally expanded vein graft balloon expandable stent is presented. Intensive
      antithrombotic treatment along with unimpeded blood flow were probably highly
      beneficial.

PMID- 9258487
TI  - Unlimiting our resources.

PMID- 9258488
TI  - Coronary angioplasty of a severe coronary stenosis at the site of a myocardial
      bridge.
AB  - We report the case of a patient who underwent coronary angioplasty for a severe
      stenosis at the site of a myocardial bridge. Although favorable angiographic
      results and the disappearance of myocardial ischemia were obtained, a significant
      pressure gradient across the lesion and abnormal myocardial fractional flow
      reserve remained immediately following angioplasty. These results suggest that
      pressure measurements may be of limited value in this subset of patients.

PMID- 9258489
TI  - Bridge work.

PMID- 9258490
TI  - Acute myocardial infarction caused by thrombotic occlusion of a coronary
      aneurysm.
AB  - We encountered an unusual case of acute myocardial infarction due to obstruction
      of a coronary aneurysm in a 38-year-old Japanese man. Although thrombolysis and
      rescue percutaneous transluminal coronary angioplasty, performed in the acute
      phase, did not result in recanalization, serial angiography and intravascular
      ultrasonography showed spontaneous recanalization and partial thrombosis within
      the aneurysmal segment during 3 months.

PMID- 9258491
TI  - Coronary angioplasty of a posterolateral branch with severe proximal vessel
      tortuosity.
AB  - We present a case of a patient who experienced recurrent angina 15 months after
      coronary bypass surgery. A single lesion distal to a graft anastomosis was
      identified in the posterolateral coronary artery. There were two severe
      angulations, each greater than 90 degrees proximal to the lesion, with access
      possible only through the saphenous vein graft to the posterior descending
      artery. For ultimate success, such challenging anatomy required a combination of
      an array of guidewires, secondary support catheters, and a deflecting balloon.

PMID- 9258492
TI  - Vasospasm in smooth coronary arteries as a cause of asystole and syncope.
AB  - In a patient with proven myocardial infarction, coronary artery disease was
      excluded angiographically. Four weeks later the patient experienced recurrent
      syncope of unknown cause. By means of Holter monitoring, ST-segment elevation
      with subsequent first-degree AV block progressing to asystole and resulting in
      loss of consciousness were documented. Treatment with gallopamil and a VVI
      pacemaker led to complete relief of all symptoms. Hence, Prinzmetal's angina may
      be a rare cause of syncope even in smooth coronary arteries.

PMID- 9258493
TI  - Successful management of Palmaz-Schatz stents deformed by inadvertent angioplasty
      outside the stents.
AB  - We describe a case in which balloon angioplasty of thrombosed saphenous vein
      graft stents resulted in compression and deformation of the stents because of
      inadvertent passage of the guidewire outside the stents. This condition was
      diagnosed by intravascular ultrasonography, which was then ultimately utilized to
      direct and optimize placement of additional stents to exclude the deformed stents
      from the vessel lumen.

PMID- 9258495
TI  - Guide catheter exchange techniques: bi-coaxial and other methods.
AB  - Maintaining the position of a guidewire across coronary artery lesions during
      angioplasty is important to allow rapid and reliable access. Stabilizing these
      small caliber angioplasty guidewires during guide catheter replacement is often
      difficult, if not impossible at times. This article reviews the techniques for
      exchanging guide catheters while maintaining coronary guidewire position. It also
      introduces the bi-coaxial guide catheter exchange technique.

PMID- 9258494
TI  - New technique for prepping the Johnson & Johnson stent delivery system.
AB  - Current prepping of the Johnson & Johnson stent deployment balloon can be
      suboptimal. This simple technique allows for an improved preparation of the stent
      delivery balloon prior to deployment, resulting in less air in the balloon during
      inflation.

PMID- 9258496
TI  - Angioplasty without the use of "Y connector": a new, easier, bloodless method.
AB  - The "Y connector" that is used in angioplasty has the following disadvantages: 1)
      it is not blood-tight; 2) we need to "screw and unscrew" every time we want to
      inject contrast material or measure the pressure; and 3) it does not allow the
      advancement of the guidewire or the balloon catheter during the injection of
      contrast material. We created a new type of connection composed of a cut sheath
      for the femoral artery, connected with a cut (at the "hub") guiding catheter. The
      aim of this study was to examine the feasibility, efficacy, and safety of the new
      method. Using the new technique we performed plain-balloon angioplasty,
      implantation of stent, and atherectomy in 350 patients. The technical success of
      the method was 100%, and no complications related to the method were seen. In
      conclusion, the novel connection that we created eliminated all the disadvantages
      of the "Y connector" and was found to have 100% technical success and safety.

PMID- 9258497
TI  - Rapid bedside coronary angiography with a portable fluoroscopic imaging system.
AB  - The ability to perform coronary angiography rapidly at the bedside has multiple
      potential applications. This study was designed to determine whether a novel
      portable angiographic system (OEC Medical Systems, series 9600, Salt Lake City,
      Utah) is capable of producing high-quality angiograms. In 29 patients (70
      vessels) undergoing elective catheterization in a conventional fixed laboratory
      (Siemens HICOR, Erlangen, Germany), we compared images obtained with the portable
      system to those from conventional fixed system. The portable system was 100%
      accurate in detecting both insignificant narrowing as well as significant
      stenoses (> 50% narrowing). There was complete concordance between systems for
      lesion location, TIMI flow, and collaterals. Thirty-two stenoses were analyzed in
      detail. Both quantitative and qualitative percent stenosis demonstrated similar
      value for lesion severity with both systems (R = 0.95, Kappa = 0.77, P < 0.001,
      respectively). Accuracy of lesion morphology by the portable system was similar
      to the fixed system (calcification 80%, eccentricity 92%). These findings
      demonstrate that a portable imaging system can produce high-quality coronary
      angiograms.

PMID- 9258498
TI  - Filmless multimedia display following cardiac catheterization.
AB  - In traditional cardiac catheterization laboratories, anatomic images are acquired
      onto 35-mm cine film and presented in series with related information days,
      weeks, or months later to an audience of decision-makers. These data are
      projected onto a convenient light-colored wall or silver screen, while
      echocardiograms and electrophysiologic data are displayed using small single-user
      computer monitors. This presentation format is not ideal, because full audience
      participation is not fostered, image quality may be degraded, and small computer
      screens can be adequataly visualized only by those individuals immediately in
      front of them. Modern video multimedia systems now make an ideal data
      presentation format practical, in which all types of media including digitally
      acquired angiograms can be displayed in parallel with full annotation, using
      large diagonal multisync color monitors. This communication discusses how to
      design a multimedia conference center in which remotely acquired filmless digital
      images can be displayed and processed together with all other pertinent cardiac
      multimedia to a large audience.

PMID- 9258500
TI  - Ventricular aneurysm and coronary artery disease: the hen and the egg?

PMID- 9258499
TI  - A case of severe intravascular hemolysis following coil occlusion of the ductus.

PMID- 9258501
TI  - Investigational intervention: revisit the paradigm or make a new one?

PMID- 9258502
TI  - n-ethylmaleimide and ethacrynic acid inhibit kinesin binding to microtubules in a
      motility assay.
AB  - Treatment of proteins in vitro with sulfhydryl (SH)-reactive compounds has been
      used successfully to determine protein regions critical for normal function. To
      probe structure-function relationships in the microtubule (MT) motor kinesin, the
      motor was treated with two SH reactive compounds, n-ethylmaleimide and ethacrynic
      acid, and its function was assayed by motility and co-sedimentation techniques.
      In the motility assay, treatment of kinesin either before or after adsorption to
      the glass surfaces of a flow cell was found to inhibit the ability of coverslip
      bound kinesin to bind to MTs. Inactivation of MT binding was slow, required high
      molar excess of the SH-reactive drug, and was very sensitive to temperature.
      Inhibition of MT binding occurred well after complete modification of kinesin
      light chain, but paralleled modification of the kinesin heavy chain. The results
      point to a model in which one critical cysteine per kinesin heavy chain is
      relatively inaccessible to solvent. Surprisingly, when the interaction between
      modified kinesin and MTs was examined by a co-sedimentation assay, kinesin
      retained the ability to bind MTs. These contrasting results may be due to
      conformational differences in the kinesin molecule that exist in the two assays.

PMID- 9258503
TI  - Patterns of microtubule assembly in taxol-treated early Drosophila embryo.
AB  - Incubation of early Drosophila embryos with low concentrations of taxol (2.3
      microM) revealed a pattern of microtubule assembly that was cell-cycle dependent.
      Microtubule bundling was observed during the pronuclear stage after resumption of
      meiosis, whereas at the onset of the first mitosis the microtubules organized in
      astral arrays. Taxol treatment showed differential microtubule assembly
      properties of the egg cytoplasm. The preferential assembly site for taxol-induced
      asters was the ventral cortex; in the dorsal cortex only microtubule bundling
      occurred. This dorsal-ventral heterogeneity of the ege cortex persisted until the
      third or fourth nuclear cycle. Microtubules did not organize in astral arrays in
      the inner cytoplasm, but only in mitotic spindles. CP190 and gamma-tubulin,
      usually found in the centrosome of the early Drosophila embryo, were absent in
      taxol-induced asters. These observations suggest that the mechanism driving the
      assembly of taxol-induced asters is not centrosome dependent in the early
      Drosophila embryo.

PMID- 9258504
TI  - Fimbrin in podosomes of monocyte-derived osteoclasts.
AB  - Fimbrin, an actin-bundling protein, is a component of the osteoclast adhesion
      complexes called podosomes. In this study, we (1) determined the localization of
      fimbrin in the mature rabbit osteoclast as well as in differentiating osteoclasts
      using the avian monocyte-derived osteoclast differentiation model, (2)
      characterized the distribution and accumulation of three fimbrin isotypes (T, L,
      and I) in avian monocytes as they fused to form multinucleate osteoclast-like
      cells, and (3) report for the first time, a close spatial relationship between
      podosomes and microtubules using fimbrin as a marker of the podosome.
      Immunofluorescence using anti-T-fimbrin, anti-L-fimbrin, and pan-isotype-anti
      fimbrin antibodies, showed that fimbrin is an integral component of the podosome
      core in the mature rabbit osteoclast and in the monocyte-derived osteoclast
      throughout differentiation. Anti-I-fimbrin, however, did not show
      immunoreactivity in these cultures. These studies also show that in the avian
      model of monocyte-derived osteoclast differentiation, day 2 cells (D2) are
      predominantly mononucleate and have few podosomes. By days 4 and 6 in culture (D4
      and D6), many cells have fused and punctate rows of podosomes are commonly
      observed at cell margins. Analysis by Western blot of protein accumulation showed
      that after an initial small rise from D2 to D4, L-fimbrin levels remained
      relatively constant from D4 to D6. However, T-fimbrin protein levels increase
      steadily from D2 to D6, suggesting that it may be related to the increase in
      podosome formation as monocytes fuse to form osteoclasts. Finally, we examined
      the distribution of podosomes relative to other cytoskeletal elements such as
      microtubules and intermediate filaments. Double immunofluorescence labeling using
      anti-fimbrin and anti-tubulin showed podosomes lying adjacent to microtubules at
      cell margins. When osteoclasts were treated with nocodazole (1 X 10(-6) M) to
      disrupt microtubules, the distribution of podosomes became more random and was no
      longer confined to the cell periphery. These results suggest that microtubule
      podosome interactions may play a role in osteoclast adhesion.

PMID- 9258505
TI  - Suppression of bleb formation, locomotion, and polarity of Walker carcinosarcoma
      cells by hypertonic media correlates with cell volume reduction but not with
      changes in the F-actin content.
AB  - The putative role of cellular or solvent volume in protrusive activity and
      locomotion has been investigated in blebbing Walker carcinosarcoma cells using
      hypertonic media. Blebbing, locomotion, and cell polarity are completely
      suppressed by 0.2 M sorbitol. The response occurs in two steps. In a first step,
      i.e. within 10 sec after the addition of sorbitol, blebbing and locomotion are
      inhibited and this is associated with an average cell volume reduction by 17%
      (corresponding to a reduction in solvent volume by 38%). It clearly precedes
      suppression of cell polarity (pre-existing protrusions, tail) occurring in a
      second step within 5 to 10 min after addition of sorbitol without additional
      reduction in the cell or solvent volume. The relative amount of F-actin does not
      correlate with the decrease in cell volume, suppression of blebbing, locomotion,
      and cell polarity. A significant decrease in the relative amount of F-actin is
      found only at volume reductions which are higher than those required to
      completely suppress blebbing, locomotion, and cell polarity. F-actin staining
      occurs preferentially along the cell membrane in isotonic as well as in
      hypertonic media. The results are best compatible with the hypothesis that
      hydrostatic pressure rather than actin polymerization at the front is the direct
      force driving the membrane forward during bleb formation. Cells with lamellipodia
      show a similar response to hypertonic media, suggesting that basically similar
      mechanisms may operate in both forms of protrusions.

PMID- 9258506
TI  - Functional interaction between Chlamydomonas outer arm dynein subunits: the gamma
      subunit suppresses the ATPase activity of the alpha beta dimer.
AB  - The alpha beta dimer and the gamma subunit of the Chlamydomonas outer arm dynein
      were solubilized by treating isolated axonemes with 0.6 M KCI, and purified by
      sucrose density gradient centrifugation. The axonemes were from an ida1 mutant to
      eliminate contamination of outer arm subunits by inner arm dynein 11, and the
      axonemes were pre-extracted with 0.6 M CH3COOK to remove non-dynein protein that
      might otherwise contaminate outer arm dynein fractions in the sucrose gradient.
      In addition, purer fractions of outer arm dynein subunits were obtained by
      modifying the centrifugation conditions to take advantage of the propensity of
      the dynein to dissociate under high hydrostatic pressure in the presence of Mg2+.
      When sucrose gradient fractions containing the gamma subunit were added to a
      fraction containing the purified alpha beta dimer under conditions expected to
      promote reassociation of the subunits to form a trimeric outer arm dynein complex
      [Takada et al., 1992: J. Biochem, 111:758-762], the total ATPase activity of the
      mixture was suppressed to a level lower than that of the original alpha beta
      dimer fraction. The inhibition paralleled the distribution of gamma subunit in
      the sucrose gradient, was saturable, and was maximum at an approximately
      equimolar ratio of the gamma subunit to the alpha beta dimer. These results
      indicate that when the gamma subunit interacts with the alpha beta dimer, the
      latter's ATPase activity is modulated downward. Previous results showed that
      interaction of the alpha subunit with the beta subunit suppressed the beta
      subunit's ATPase activity [Pfister and Witman, 1984: J. Biol. Chem. 259:12072
      12080]. Thus, the total ATPase activity of the outer arm dynein is dependent upon
      communication between all three subunits within the arm.

PMID- 9258507
TI  - Transient disruptions of axonemal structure and microtubule sliding during bend
      propagation by Ciona sperm flagella.
AB  - Demembranated sperm flagella of Ciona were reactivated at increased salt
      concentrations (0.45 to 0.5 M K acetate). In addition to a decrease in amplitude
      of propagated bends, some flagella switch between "stable" and "transient"
      bending cycles. In the transient bending cycles, there is increased
      intermicrotubule sliding, in the direction that forms a new principal bend at the
      base of the flagellum, during the first half of a bending cycle. The magnitude of
      this increased sliding may be as much as 1 radian, or 0.06 micron between
      adjacent doublet microtubules. Most transient bending patterns also show a
      characteristic disruption of axonemal structure, involving separation between
      strands of microtubule doublets over a distance of up to 5 microns, occurring
      within a principal bend, typically about 16 microns from the base of the
      flagellum. The disruptions usually disappear after the principal bend propagates
      beyond the region of the disruption. Formation of these disruptions requires
      additional sliding, in the direction that would form a principal bend at the base
      of the flagellum, of up to about 0.3 micron. Formation of these disruptions may
      be explained by weakening of structural interactions by increased salt
      concentration and transverse forces, proportional to curvature and transmitted
      force, that will tend to separate doublets in a bend. These observations indicate
      that an actively beating flagellum possesses active sliding capability that is
      activated but not expressed during normal bend initiation and propagation. The
      initiation and propagation of flagellar bends may not be explicable solely in
      terms of local activation and inactivation of dynein-driven sliding.

PMID- 9258509
TI  - Extent of radial sarcomere coupling revealed in passively stretched cardiac
      myocytes.
AB  - The complex geometry of the heart leads to a time-varying and nonuniform
      distribution of stress and strain on the myocardium during the cardiac cycle.
      This study investigated the sarcomere length and striation registration behavior
      resulting from a gradient of strain imposed on the cytoskeleton of isolated
      cardiac myocytes. Within a myocyte, sarcomeres are organized into domains
      separated by strips of mitochondria and nuclei. Sarcomeres are interconnected
      radially at the Z-disc by the exosarcomeric cytoskeleton, composed primarily of
      the intermediate filament desmin. Chemically skinned myocytes isolated from adult
      rat hearts were attached using to concentric double-barreled pipettes in such a
      way as to induce a gradient of applied strain across the width of the cell. At
      rest lengths, there was variation in the sarcomere length between domains of
      attached cells. Upon stretch, most domains exhibited proportional increases in
      sarcomere length, with the initial differences being maintained. However, some
      domains did not behave in synchrony with the others at shorter sarcomere lengths.
      Thus, the coupling between sarcomeric domains can allow for a non-linear
      relationship between sarcomere length and strain. Sarcomeres were tightly coupled
      in the radial direction within a single domain, but striation mis-registration of
      up to 0.20 micron between domains was induced by stretch. This indicates the
      looser nature of the cytoskeletal coupling between domains compared to that
      within domains. Thus, cardiac myocytes are not rigid functional units, but
      composite structures whose components consist of functionally semi-independent
      domains tethered by the cytoskeletal intermediate filament lattice.

PMID- 9258508
TI  - Distribution and orientation of rhodamine-phalloidin bound to thin filaments in
      skeletal and cardiac myofibrils.
AB  - Phalloidin staining of muscle does not reflect the known disposition of
      sarcomeric thin filaments. Quantitative image analysis and steady-state
      fluorescence polarization microscopy are used to measure the local intensity and
      orientation of tetramethyl rhodamine-labeled phalloidin (TR-phalloidin) in
      skinned myofibrils. TR-phalloidin staining of isolated skeletal myofibrils
      labeled while in rigor reveals fluorescence that is brighter at the pointed ends
      of the thin filaments and Z lines than it is in the middle of the filaments. In
      cardiac myofibrils, phalloidin staining is uniform along the lengths of the thin
      filaments in both relaxed and rigor myofibrils, except in 0.2-micron dark areas
      on either side of the Z line. Extraction of myosin or tropomyosin-troponin
      molecules does not change the nonuniform staining. To test whether long-term
      storage in glycerol changes the binding of phalloidin to thin filaments in
      myofibrils, minimally permeabilized (briefly skinned) myofibrils, or myofibrils
      stored in glycerol for at least 7 days (glycerol extraction) were compared. TR
      phalloidin was well ordered throughout the sarcomere in briefly skinned skeletal
      and cardiac myofibrils, but TR-phalloidin bound to the Z line and pointed ends of
      thin filaments was randomly oriented in glycerol-extracted myofibrils, suggesting
      that the ends of the thin filaments become disordered after glycerol extraction.
      In relaxed skeletal myofibrils with sarcomere lengths greater than 3.0 microns,
      staining was nearly uniform all along the actin filaments. Exogeneous bare actin
      filaments polymerized from the Z line (Sanger et al., 1984: J. Cell Biol. 98:825
      833) in and along the myofibril bind rhodamine phalloidin uniformly. Our results
      support the hypothesis that nebulin can block the binding of phalloidin to actin
      in skeletal myofibrils and nebulette can block phalloidin binding to cardiac thin
      filaments.

PMID- 9258510
TI  - Use of allogeneic bone marrow labeled with neomycin resistance gene to examine
      bone marrow-derived chimerism in experimental organ transplantation.
AB  - Posttransplant infusion of viable donor bone marrow cells (DBMC) has been shown
      in our previous studies to promote acceptance of incompatible kidney allografts
      in rhesus monkeys after treatment with polyclonal antithymocyte globulin to
      deplete peripheral T-lymphocytes. In this nonhuman primate model, the infusion of
      the DBMC is requisite for the induction of functional graft tolerance and
      specific MLR and CTLp unresponsiveness, although the relevant role and fate of
      bone marrow-derived chimeric cells is uncertain. Standard immunological and
      molecular techniques applied to this monkey model are unable to differentiate
      between chimeric cells derived from the infused DBMC and those derived from
      allograft-borne passenger leukocyte emigrants. To distinguish chimerism due to
      infused DBMC, we transduced DBMC with a functional neomycin resistance gene
      (Neo(r)) using the retroviral vector pHSG-Neo.Neo(r)-transduced BMC were infused
      into recipients approximately 2 wk after kidney transplantation and treatment
      with rabbit antithymocyte globulin. No maintenance immunosuppressive drugs were
      given. Genomic DNA isolated from peripheral blood leukocytes was used to monitor
      the presence ofNeo(r)-positive cells. Tissue samples obtained at necropsy also
      were assessed forNeo(r)-positive chimeric cells. The presence of DBMC-derived
      chimerism was assessed by polymerase chain reaction usingNeo(r) sequence-specific
      primers (PCR-SSP). Chimerism was detectable in recipient tissues at various times
      for up to 6 mo after DBMC infusion. These studies using gene transduction
      methodology indicate that a stable genetic marker can provide capability to
      examine DBMC-derived chimerism for prolonged periods in a nonhuman primate model.
      This approach should facilitate future studies in preclinical models to study the
      role and type of chimeric cell lineages in relation to functional allograft
      tolerance.

PMID- 9258511
TI  - Analysis of hepatocyte distribution and survival in vascular beds with cells
      marked by 99mTC or endogenous dipeptidyl peptidase IV activity.
AB  - Knowledge of the kinetics of cell distribution in vascular beds will help
      optimize engraftment of transplanted hepatocytes. To noninvasively localize
      transplanted cells in vivo, we developed conditions for labeling rat hepatocytes
      with 99mTc-pertechnetate. The incorporated o9mTc was bound to intracellular
      proteins and did not impair cell viability. When 99mTc hepatocytes were
      intrasplenically injected into normal rats, cells entered liver sinusoids with
      time-activity curves demonstrating instantaneous cell translocations. 99mTc
      activity in removed organs was in liver or spleen, and lungs showed little
      activity. However, when cells were intrasplenically transplanted into rats with
      portasystemic collaterals, 99mTc appeared in both liver sinusoids and pulmonary
      alveolar capillaries. To further localize cells, we transplanted DPPIV+ F344 rat
      hepatocytes into syngeneic DPPIV-recipients. Histochemical staining for DPPIV
      activity demonstrated engraftment of intrasplenically transplanted cells in liver
      parenchyma. In contrast, when 99mTc hepatocytes were injected into a peripheral
      vein, cells were entrapped in pulmonary capillaries but were subsequently broken
      down with redistribution of 99mTc activity elsewhere. Intact DPPIV+ hepatocytes
      were identified in lungs, whereas only cell fragments were present in liver,
      spleen, or kidneys. These findings indicate that although the pulmonary vascular
      bed offers advantages of easy accessibility and a relatively large capacity,
      significant early cell destruction is an important limitation.

PMID- 9258512
TI  - Alginate polylysine microcapsules as immune barrier: permeability of cytokines
      and immunoglobulins over the capsule membrane.
AB  - Transplantation of pancreatic islets in alginate polylysine microcapsules is a
      potential useful method for treating type I diabetes. In this study, the
      permeability for alginate-polylysine microcapsules to cytokines an
      immunoglobulines has been investigated by a newly developed method. Magnetic
      monodisperse polymer particles (Dynabeads) coated with antibodies against
      selected proteins were encapsulated in 0.7 mm alginate polylysine microcapsules.
      The capsule membrane permeability to IgG (150 kDa), Transferrin (81 kDa), Tumor
      necrosis factor (TNF, 51 kDa), Interleukin-1 beta (IL-1 beta, 17.5 kDa), and
      insulin (5.8 kDa) was estimated by measuring the binding of 125I-labeled proteins
      to the encapsulated antibody coated Dynabeads. Capsules with an inhomogeneous
      solid gel core were made of alginates with high guluronic or high mannuronic acid
      content and poly-L (PLL)- or poly-D-lysine (PDL) of concentrations varied from
      0.05-0.2%. The various capsules examined were all impermeable to IgG. The
      capsules made with a PLL-, but not PDL-membranes were permeable for transferrin.
      IL-1 beta was found to penetrate all of the different capsule types. The high-G
      capsules, however, could be made impermeable to TNF and still allowed transferrin
      to pass. The permeability of these capsules to IL-1 beta, but not to TNF was
      confirmed in an assay where mouse islets of Langerhans were incubated with TNF
      and IL-1 beta, and comparing the IL-6 for encapsulated and non-encapsulated
      islets.

PMID- 9258513
TI  - Towards the development of a bioartificial pancreas: effects of poly-L-lysine on
      alginate beads with BTC3 cells.
AB  - A bioartificial tissue construct that consists of insulin-secreting cells
      entrapped in an alginate/poly-L-lysine (PLL) matrix offers a promising approach
      for the treatment of type I diabetes. Use of transformed cells has been proposed
      as a solution to the cell availability problem posed by islets. The growth
      characteristics of transformed cells in their sequestered environment and the
      effects of PLL on their metabolic and secretory activities have not yet been
      characterized. Our data demonstrate that mouse insulinoma beta TC3 cells
      proliferate while they are entrapped in both PLL-free and PLL-coated alginate
      beads. During this process, cell aggregates develop in the bead periphery, which
      increase in number and size with time. PLL is crucial for the long-term in vitro
      structural stability of beads, and it does not appear to affect the metabolic and
      secretory activities of entrapped beta TC3 cells. The implications of these
      findings in the development of a bioartificial pancreatic construct based on
      transformed cells are discussed.

PMID- 9258514
TI  - Histochemical analysis of the role of class I and class II Clostridium
      histolyticum collagenase in the degradation of rat pancreatic extracellular
      matrix for islet isolation.
AB  - To understand why class II Clostridium histolyticum collagenase is much more
      effective than class I in the isolation of rat pancreatic islets, we analyzed the
      role of these collagenases in pancreatic tissue dissociation. Crude collagenase
      was purified and then fractionated into class I and II with different enzyme
      activities and protein compositions. Pancreatic tissue was incubated with either
      class I, class II, or class I + II, with or without added protease, under
      conditions that eliminated endogenous proteolytic activity. The degradation of
      pancreatic extracellular matrix was monitored by selective histochemical staining
      of tissue samples. Class I and II showed similar capacities to degrade
      glycoproteins and degraded about one-third of the glycoproteins during 120 min of
      incubation. The degradation of collagens by class I and II was relatively more
      effective, 80 to 95% of the collagens being removed in 120 min, and also class
      dependent. Both in the presence and absence of protease, class II was more
      effective at degrading collagens than class I, but this difference in efficacy
      was less apparent than with islet isolation. Class I + II degraded collagens
      faster and more complete than did the individual classes, indicating a
      synergistic effect of class I and II. Evaluation of collagen degradation at
      various pancreatic locations did not show a selective degradation of collagens by
      any of the collagenase classes. The present data offer a partial explanation for
      the major role of class II in islet isolation.

PMID- 9258515
TI  - Control of insulin secretion and glucose homeostasis in exercising diabetic rats
      with intrasplenic or kidney subcapsular islet grafts.
AB  - This study was designed 1) to investigate mechanisms of insulin secretion during
      exercise after transplantation of islets in the spleen and under the kidney
      capsule, and 2) to compare these organs as transplantation site regarding an
      adequate portal or systemic delivery of insulin and glucose homeostasis during
      exercise. Diabetic rats were provided with 5 microL isogenic islet tissue in the
      spleen or under the kidney capsule, which results in normoglycemia, and were
      submitted to a swimming test. Portal plasma insulin levels were higher than
      simultaneously sampled systemic insulin levels in the control and in the
      intrasplenic islet grafted group, but not in the kidney subcapsular islet-grafted
      group. Plasma portal and systemic insulin levels decreased, and glucose levels
      increased during exercise in all groups. The exercise-induced increase in levels
      of catecholamines was larger in systemic than in portal plasma, suggesting
      catecholamine extraction by the lungs or intestines. The experiments were
      repeated after removing of adrenal medulla, resulting in nondetectable or very
      low plasma adrenaline levels. Despite these low adrenaline levels, insulin levels
      decreased during exercise. The results indicate that 1) the exercise-induced
      reduction of insulin secretion is not mediated by circulating adrenaline, but is
      probably under control of the sympathetic nervous system, which could be the
      result of reinnervation of the transplanted islets. 2) Although a portal-systemic
      insulin gradient was absent in rats with kidney subcapsular islet grafts, the
      absence of a difference in glucose homeostasis during exercise between the sites
      revealed that all investigated sites are preferential to transplant islets.

PMID- 9258516
TI  - Hypoosmotic exposure of canine pancreatic digest as a means to purify islet
      tissue.
AB  - The development of more effective means to separate pancreatic islets from the
      unwanted exocrine tissue would greatly advance the field of clinical islet
      allotransplantation in the treatment of insulin-dependent diabetes mellitus.
      Recent experiments with hamster islets have demonstrated a selective destruction
      of dissociated single exocrine cells when exposed to hypotonic conditions. It was
      the aim of this study to extend these observations to the canine model with
      collagenase dissociated pancreatic tissue and to evaluate the treatment's effect
      on islet function. Pancreases from five mongrel dogs were digested using an
      automated protocol of intraductal delivery of collagenase, and gentle
      dissociation. Duplicate samples of pancreatic digest were removed for insulin and
      amylase determination prior to and immediately following exposure to 50 mOsm/kg
      salt solution for a period of 30, 60, or 300 s before returning the digest to
      isoosmotic conditions. The remaining digest was cultured for a period of 48 h at
      37 degrees C before the tissue was recombined, washed, and a third sample removed
      for insulin and amylase. In vitro viability was then assessed using a static
      incubation assay with insulin content measured using a double-antibody
      radioimmunoassay, and amylase was determined using a colorimetric assay system.
      No difference in the insulin or amylase levels between the experimental groups
      was observed immediately following the hypotonic exposure; however, a significant
      decrease in the amylase content was observed following the 48-h culture period in
      digest that had been hypoosmotically exposed for 60 or 300 s compared with the
      pretreatment group (2.83 +/- 0.41 IU amylase/mg pancreas vs. 1.29 +/- 0.21 and
      0.83 +/- 0.12, mean +/- SEM, p < 0.05). Insulin content was also significantly
      reduced in the 300-s exposure group compared with nontreated controls (3.2 +/-
      0.6 mU insulin/mg pancreas vs. 2.0 +/- 0.2). The insulin/ amylase ratio (I/A), a
      measure of islet and exocrine content, was 1.1 +/- 0.13 following pancreas
      dissociation and 1.34 +/- 0.21 for control tissue cultured for 48 h. The I/A
      ratio increased following hypoosmotic exposure to 1.50 +/- 0.31 for tissue
      exposed for 30 s, 1.77 +/- 0.19 for 60-s exposure, and 2.54 +/- 0.13 for tissue
      exposed for 300 s (p < 0.05, vs. pretreatment group). In vitro insulin secretion
      was equivalent with the exception of the tissue exposed for 300 s, which had an
      increased basal level of insulin resulting in a significantly decreased
      stimulation index (3.8 +/- 0.5 vs. 8.1 +/- 1.2 for the purified islet control
      group, p < 0.05). These results suggest that a brief hypotonic exposure to
      pancreatic digest can alter the insulin/amylase ratio; however, there is a
      functional impairment on subsequent islet function after a period of in vitro
      tissue culture.

PMID- 9258517
TI  - Successful reversal of diabetes by single donor isologous islet transplantation
      in a mouse model.
AB  - A method for isolating mouse islets which consistently gives a high yield with
      good purity is described. Using a bovine serum albumin gradient, the mean yield
      of islets per pancreas is 425 (SEM +/- 15) with a consistent purity of over 90%.
      Single donor to single recipient of islets transplanted under the renal capsule
      restores normoglycemia in the diabetic recipients within 2 to 5 days of
      transplantation.

PMID- 9258518
TI  - A rapid and sensitive cellular enzyme-linked immunoabsorbent assay (CELISA) for
      the detection and quantitation of antibodies against cell surface determinants.
      II. Optimal reagent concentrations and predictive analysis.
AB  - A cellular enzyme-linked immunosorbent assay (CELISA) was developed for the
      detection and quantification of antibodies elicited against allogeneic cell
      surface determinants. The technique uses a solid-phase cell matrix created by
      fixing cells with a mild formalin solution onto the bottom of a 96-well
      microtiter plate. A primary layer of alloantisera is first reacted against rat
      target cells. The secondary antibody, peroxidase conjugated antirat IgG, is then
      added to each well and serves as the second sandwich layer. Optimal reagent
      concentrations were determined by serial dilution analysis of various cell
      concentrations and secondary antibody dilutions. It was found that 200,000 cells
      per well was the optimal target cell concentration. However, 100,000 cells per
      well was also sufficient to run the assay with acceptable performance
      characteristics. Even lower cell concentrations of 10,000 and 20,000 cells/well,
      although not optimal, also produced acceptable results. Secondary antibody
      concentration with respect to the optimal cell concentration was determined to be
      1:500. At 200,000 cells per well and a 1:500 secondary antibody dilution, the
      assay presented excellent coefficients of determination and high positive to
      negative ratios. The reaction was found to be very sensitive in yielding high
      antibody titers with low background levels and could be defined mathematically as
      a linear-log function. Titers of multiple unknown alloantibody samples were
      easily and accurately predicted in an automated manner by regression analysis
      form known standards. This immunoassay will be useful in studies of cell surface
      determinant expression and quantitation of antibodies reactive to such markers.

PMID- 9258520
TI  - Co-transplantation of plasmid-transfected myoblasts and myotubes into rat brains
      enables high levels of gene expression long-term.

PMID- 9258519
TI  - An Internet multicast symposium concerning the microcirculation of the islets of
      Langerhans.
AB  - The Internet Globally-linked Computer System was used to conduct an international
      scientific symposium. The symposium was held at the VAMC-Long Beach and consisted
      of prepared lectures that were multicast over the Internet. The basic unit of
      hardware used for the Internet Multicast was the Silicon Graphics Indy Unix
      Workstation, which was equipped with a color video camera. The multicast required
      four additional pieces of software from the file transfer protocol. The multicast
      backbone protocol allowed for simultaneous audio and video signals (the
      presenter, the slides, and the videotape images of islet microcirculation
      studies) to be transmitted over the computer network. The faculty included 12
      experts in microcirculation, who gave 15-min lectures that included a question
      and answer period. All lectures were received at 14 computer stations in six
      countries. Eleven of the faculty gave their lectures at the VAMC-Long Beach, and
      one gave her lecture at the Massachusetts Institute of Technology in Boston, MA.
      The presenter from Boston was able to receive and answer questions from the
      faculty at the VAMC-Long Beach. An estimated $12,000 was saved in travel, hotel,
      and food costs and an estimated 180 travel hours were saved by viewers who did
      not have to travel to the symposium. We have demonstrated that a scientific
      symposium can be conducted using the Internet. We propose that many of our future
      meeting will be organized over the computer network. This format of multiimage
      projections allows us to effectively communicate in a personal way with a
      reduction in expensive and time-consuming travel.

PMID- 9258521
TI  - The PREMAP Study: prevalence and risk factors of dementia and clinically
      diagnosed Alzheimer's disease in Provence, France. Prevalence of Alzheimer's
      Disease in Provence.
AB  - The PREMAP Study investigated the prevalence and risk factors of dementia and
      Alzheimer's Disease (AD) in a random sample of 1062 residents 70 year old or
      more, living in south-eastern France (private homes and institutions). All
      persons living in institutions for the elderly (n = 258) and community dwellers
      (n = 804) scoring less than 24 points on the MMSE (18.4%) were invited to undergo
      a medical evaluation at home by a qualified neurologist using the CERAD battery.
      We found 177 cases of dementia (9.2%), including 82 cases of AD (5.5%).
      Prevalence of AD increased significantly with age and was higher among women (OR:
      4.24) and persons with no formal educational level (OR: 2.47). While a MMS score
      less than 24 was more frequent among persons with a foreign native language (OR:
      3.05), the OR and AD was not significantly associated with native language. The
      proportion of AD among persons suffering from senile dementia was 45% among
      elderly living in institutions and 69% among those living in the community.
      Prevalence rates in south-eastern France are similar to the average rates for
      Europe. This study underlines the need to investigate the relationships between
      native language, MMSE and AD on the one hand, and the link between a low MMSE
      score and institutionalisation of patients suffering from AD on the other.

PMID- 9258522
TI  - Demographic and behavioral predictors of knowledge and HIV seropositivity:
      results of a survey conducted in three anonymous and free counselling and testing
      centers.
AB  - This paper deals with subjects seeking counselling and testing for human
      immunodeficiency virus (HIV); it analyses which sociodemographic and behavioral
      characteristics are related to beliefs concerning HIV infection and to HIV
      seropositivity. A one month survey among individuals who attended HIV testing in
      three anonymous and free centers (CIDAGs) was carried out in Paris city, on March
      1994. 2059 subjects completed a self-administered questionnaire. Data collected
      included demographic information, sexual and IVDU behavior, and HIV
      seropositivity. Subjects also had to evaluate their own risk of getting the
      acquired immunodeficiency syndrome (AIDS) and the perceived risk of getting AIDS
      in specific situations such as unprotected anal/vaginal intercourse with a casual
      partner, with multiple partners, with a seropositive partner, current dental
      treatment, French kiss, etc.... Multiple linear and logistic regressions have
      been used to model the dependent variables. Subjects correctly evaluated the risk
      level of HIV transmission associated with different situations, and women, young
      men and those engaged in homo/bisexual behavior were in general more conscious of
      the increased danger resulting from high risk sexual practices. Among males,
      homo/bisexuals, drug users and the less educated considered themselves to be more
      at risk. The most important factors related to HIV seropositivity were sexual
      orientation, intravenous drug use (IVDU), and the perceived risk of getting aids.
      Despite a good awareness of HIV contamination and an accurate perception of their
      own risk, many subjects continued to engage in high risk AIDS activities. Better
      targeted interventions need to be developed to promote and maintain behavior
      changes.

PMID- 9258523
TI  - Estimating the size of the HIV epidemic among injecting drug users in Amsterdam.
AB  - Aim of this study was to assess the cumulative incidence of HIV-infection, AIDS
      and pre-AIDS death in the population of injecting drug users (IDU) in Amsterdam.
      By assuming equivalence, between a cohort of IDU and the IDU population, of the
      ratios of incidences of AIDS and pre-AIDS death to the number of HIV positive
      persons giving rise to these incidences, the numbers of HIV positive persons and
      pre-AIDS deaths in the population could be calculated, given that other
      parameters were known. Cohort study data on HIV prevalence and incidences of HIV
      infection, AIDS, and pre-AIDS death, were combined with national AIDS
      surveillance data. As of 1 October 1994, the estimated cumulative number of HIV
      positive IDU in Amsterdam was approximately 1280, far higher than a recent back
      calculation estimate. Of the 1280, 204 HIV positive IDU had been diagnosed with
      AIDS, while about 270 had died pre-AIDS. The HIV prevalence of IDU residing in
      Amsterdam that were still alive and free of AIDS was hence estimated at around
      800. Since the incidence of pre-AIDS death and AIDS exceeded the number of
      seroconversions during the past four years, the HIV epidemic among IDU in
      Amsterdam appears to be dwindling. A lower bound of the number of HIV positive
      IDU being alive, AIDS-free and living elsewhere in the Netherlands was roughly
      estimated at 600. Because of untimely deaths, only a limited number of HIV
      positive IDU can be expected to be diagnosed with AIDS in the future. Since these
      estimates are based upon some rather bold assumptions, they should be interpreted
      with caution and require further validation by independent sources.

PMID- 9258524
TI  - Quitting smoking in northern Italy: a cross-sectional analysis of 2621 subjects.
AB  - To describe the relationship between sociodemographic factors, life-style habits,
      selected dietary indicators, smoking-related variables, and quitting smoking we
      analyzed data derived from the comparison group of a case-control study of
      colorectal and breast cancers based on a network of teaching and general
      hospitals in Northern Italy. A total of 2621 subjects (1215 women and 1406 men)
      who were ever cigarette smokers were included for analysis. Age-adjusted rates of
      stopping smoking (quit rates) and multivariate odds ratios (OR) of quitting
      smoking were computed. The overall age-adjusted quit rate was 38.6% for males and
      24.9% for females, corresponding to an OR of quitting of 0.6 (95% CI: 0.5-0.7)
      for females vs males. The quitting rate increased with increasing age. After
      allowing for age, smoking cessation was more frequently reported by more educated
      or higher social class individuals. No relationship was present between quitting
      smoking and alcohol consumption, but quitting smoking was inversely related to
      coffee consumption. The probability of quitting smoking increased directly with
      number of cigarettes among males but not among females, who showed a J-shaped
      pattern. Older, heavy smokers were more likely to give up smoking. A general
      pattern of increasing rates of quitting smoking with higher consumption of
      vegetables and fruit, and hence beta-carotene, was present. This study confirms a
      positive association between quitting smoking and increasing age, higher
      education, low coffee consumption, heaviness of smoking and high consumption of
      vegetables and fruit.

PMID- 9258525
TI  - Prevalence of hepatitis A, B and C in the Flemish population.
AB  - Viral hepatitis is a serious health problem throughout the world. No recent
      prevalence data on hepatitis A, B and C were available for the population in
      Flanders, Belgium. For this reason, a sero-epidemiological study was undertaken
      in 1993-1994 in a sample of the general population. The purpose of this study was
      to obtain a clear picture of the prevalence of hepatitis A, B and C. Between
      April 1993 and February 1994, 4,058 blood samples were drawn and collected in 10
      hospitals in Flanders. The study group was representative for the Flemish
      population. For hepatitis A a seroprevalence of 55.1% was found. In the non
      Belgian residents the HAV prevalence was significantly higher than in Belgians
      (62% versus 52%; chi2 = 8.05; p = 0.005). For hepatitis B. 9.9% of the study
      group showed serological evidence of hepatitis B markers: 6.9% of the
      participants was positive for anti-HBs/anti-HBc, 0.7% appeared to be HBsAg
      positive and 3.5% was solely anti-HBs positive. The prevalence of HBV markers in
      Belgians was 6.9%, significantly lower compared to the 13.4% among non-Belgians
      (chi 2 = 14.05; p = 0.00018). 4055 serum samples were analysed for hepatitis C
      serology by second generation anti-HCV tests. Anti-HCV was detected in 0.87% of
      the serum samples. No statistically significant difference was found in HCV
      prevalnece between Belgians and non-Belgians. Results of this study should help
      policy makers in their decisions on the most appropriate hepatitis A and B
      vaccination strategy and on the most effective prevention strategy for hepatitis
      C.

PMID- 9258526
TI  - Cancer mortality among chemical workers in an Italian plant.
AB  - Objective of this study was to assess the mortality experience of a cohort of
      chemical workers at a plant located in central Italy. Subjects employed for any
      time between 1954 and 1970 at the chemical plant were included in the cohort and
      followed up to June 1991. The workers were classified as having ever/never worked
      in one of the following work processes: organic chemicals, acid mixtures,
      cleansing agents and insecticides. Mortality experience of the cohort was
      compared with that of the regional population by computing SMRs (standardized
      mortality ratios) and 90% CI (confidence intervals). Vital status was ascertained
      for 96% of the 505 cohort members. All causes of mortality for the entire cohort
      were lower than expected (Obs: 176; SMR: 0.90; 90% CI: 0.79-1.03). Analysis by
      work process revealed an increased mortality for lymphatic and hematopoietic
      tissue neoplasm in the cleansing agents department (Obs: 3; SMR: 5.00; 90% CI:
      1.36-12.9); peritoneum and retropertioneum neoplasm in the organic compounds
      production (Obs: 2; SMR: 13.33; 90% CI: 2.37-42.0), and bladder cancer in the
      insecticides process (Obs: 3; SMR: 3.53; 90% CI: 0.96-9.12). Although the study
      had a low statistical power, the increased cancer risks detected are consistent
      with previous observations and may be of etiologic interest.

PMID- 9258528
TI  - A new approach to tracking of subjects at risk for hypercholesteremia over a
      period of 15 years: The Amsterdam Growth and Health Study.
AB  - Because 'traditional' tracking analyses have some drawbacks, this paper presents
      a new method, which is based on generalized estimating equations (GEE). The new
      method is illustrated with data from the Amsterdam Growth and Health Study. In
      this observational longitudinal study six repeated measurements were carried out
      on 181 subjects (initial age 13 years) over a period of 15 years. Tracking was
      assessed for total cholesterol (TC), high density lipoprotein (HDL) and the
      TC/HDL ratio by calculating the odds ratio (OR) for subjects at risk at the age
      of 13 years regarding the development of their risk status over a 15 year period.
      These ORs can be interpreted as tracking coefficients. Three methods were
      compared: percentage of subjects who maintain their position in a certain risk
      group (i.e. univariate logistic regression), multivariate logistic regression and
      GEE. The three methods differ in the possibility of using all available data in
      the analysis and in the possibility of adjusting for certain covariates. Based on
      this, the GEE-approach seemed to be the most appropriate to calculate tracking
      coefficients for subjects at risk. When the risk groups were defined according to
      objective (absolute) risk values, for TC the GEE-OR was 10.1 (95% confidence
      interval (CI) 5.0-21.9), for HDL 14.4 (95% CI 7.2-28.7) and for the TC/HDL ratio
      25.5 (95% CI 11.5-56.8). It can be concluded that the GEE-approach is very
      suitable to assess tracking for subjects at risk.

PMID- 9258527
TI  - Simultaneous influenza and pneumococcal vaccination in elderly individuals.
AB  - The study was performed to evaluate the effects of influenza and pneumococcal
      vaccines administered alone or in combination. 124 elderly subjects living in
      community were vaccinated either with influenza split vaccine or with
      pneumococcal 23-valent or with both vaccines at the same time in different sites.
      Sera were tested for hemoagglutination inhibiting antibodies for influenza and
      for antibodies against 23-valent vaccine for streptococcus pneumoniae. No side
      effects were observed in the vaccinated population. Serological results indicated
      that influenza vaccine increased significantly antibody levels. No difference was
      observed between the group which received influenza vaccine alone and that which
      received influenza and pneumococcal vaccines associated, considering either G.M.T
      or the percentages of protected individuals or the percentages of subjects who
      seroconverted. When pneumococcal vaccine was administered at the same time with
      influenza vaccine, there was a not statistically significant reduction in both
      mean antibody concentration and mean fold increase. It is concluded that the
      simultaneous administration of influenza and pneumococcal vaccines to elderly
      individuals, including subjects at risk, is safe, effective and economically
      advantageous.

PMID- 9258529
TI  - Prevalence and control of arterial hypertension in the south-east of Spain: a
      radical but still insufficient improvement.
AB  - Stroke mortality rates in Spain are one of the highest in all of Europe. At the
      same time, the Murcia region (south-east Spain) shows, for both genders, the
      highest age-adjusted stroke mortality rates in all of Spain. The earliest
      available hypertension figure estimations for this area go back to 1981, when a
      high prevalence combined with an almost nonexistent control was detected. One
      decade later, updated prevalence estimations of hypertension are presented
      jointly with their degree of control and their association with other risk
      factors based on the results of a prevalence survey in a random population sample
      (n = 3,091). Arterial blood pressure was measured following the MONICA protocol,
      maintaining a tight quality control on between and within-observer variability.
      As hypertensive was considered any person with systolic blood pressure (SBP) > or
      = 140 mmHg or with diastolic blood pressure (DBP) > or = 90 mmHg or with
      antihypertensive pharmacological treatment. Detected prevalence rises to 32.3%
      (CI 95%: 29.1%-35.5%) among males and to 23.7% (CI 95%: 21.4%-26%) among females,
      maintaining its level regarding figures observed back in 1981. However, its
      control has been increased, especially among hypertensive women [from less than
      5% in 1981 to 35% (95% CI: 32%-37.8%) at present]. Hypertension is strongly
      associated to hipercholesterolemia, overweight, obesity and diabetes (p < 0.01).
      On the contrary, it shows an opposite association with current smoking, higher
      educational level and leisure time physical activity (p < 0.01). The highest
      educational level was associated with better hypertension treatment and control.
      In summary, while hypertension prevalence is stabilized in our population, its
      control has improved in a measurable but still insufficient way. These results
      are in accordance with a decreasing trend in stroke mortality registered in the
      Murcia Region along the last decade.

PMID- 9258530
TI  - Comparison between estimates of hand volume and hand strengths with sex and age
      with and without anthropometric data in healthy working people.
AB  - Edema and hand strength measurements are useful for the recovery assessment of
      patients with a hand lesion. This work determined and compared estimates of hand
      volume, grip strengths (measured with a Jamar and a Collins dynamometer), and
      pinch strength (with a Jamar pinch gauge) in terms of sex and age with or without
      anthropometric indices in healthy working people. The sample included 100
      subjects from within the staffs of two rehabilitation centres. For both grip
      strengths, multiple linear regression models including body height, weight, and
      arm muscle area were very good (multiple correlation coefficient R of about 0.84)
      and clearly better than those obtained with sex and age only. For pinch strength,
      the best estimate was obtained with sex and arm muscle area (R of 0.76); for hand
      volume, the model with sex, body height, and weight provided the best result (R
      of 0.93). These findings suggested that anthropometric indices easy to measure
      must be taken into account to estimate hand volume and hand strengths.

PMID- 9258531
TI  - Pattern of bacterial meningitis in Italy, 1994.
AB  - During 1994, 603 cases of bacterial meningitis were reported in Italy. Seventy
      five percent of cases with determined etiology was due to three agents: Neisseria
      meningitidis (33.4%), Streptococcus pneumoniae (23.4%) and Haemophilus influenzae
      (18.6%). The majority of cases due to N. meningitidis and H. influenzae occurred
      in subjects below five years of age (35.7% and 84.8%, respectively) while S.
      pneumoniae accounted for 52.8% of meningitis cases in subjects older than 44 year
      of age. The estimated incidence of N. meningitidis on the national population in
      1994 was 0.27 per 100,000. Serogroup B accounted for 62.5% of the serotyped
      isolates, group C for 23.1%, group A for 7.2%, group W135 for 3.6%, group Y for
      1.8%. All tested meningococcal strains were susceptible to penicillin as well as
      to rifampin. Incidence of meningococcal meningitis in 1994 has been low
      suggesting that its relative importance compared to other bacteria causing
      meningitis is likely to change in the future. Therefore, extended surveillance on
      bacterial meningitis by other etiological agents has to be maintained and
      implemented in order to undertake the appropriate control measures and evaluate
      their effect.

PMID- 9258532
TI  - Microbiologic data overview of Italian cystic fibrosis patients.
AB  - The aim of our study was to determine the frequency of microbiological culturing
      and prevalence of colonization by principal pathogens of the respiratory tract of
      Italian cystic fibrosis patients. Data on all Italian cystic fibrosis patients
      were collected using a questionnaire sent to all Italian CF Centers. Results were
      obtained of microbiological cultures from 2,521 patients. Information was gained
      regarding the method of gathering biological samples, the percentage of patients
      undergoing microbiological culturing regularly, the procedures used to isolate
      bacteria and types of culture media used which were selective for Burkholderia
      cepacia. Ninety-four percent of Italian CF patients are regularly tested
      microbiologically. Sputum and pharyngeal cultures are most often carried out. 49%
      of Italian patients are colonized by Staphylococcus aureus, 5.4% by Haemophilus
      influenzae, 48.9% by Pseudomonas aeruginosa and 3.8% by Burkholderia cepacia. In
      Italy there is a high prevalence of CF patients colonized by Staphylococcus
      aureus and a low prevalence of patients colonized by Haemophilus influenzae. The
      prevalence of Burkholderia cepacia and Pseudomonas aeruginosa does not differe
      significantly from other countries examined.

PMID- 9258533
TI  - Specific detection of Coxiella burnetii through partial amplification of 23S
      rDNA.
AB  - A previously published sequence of the 23S rRNA gene of Coxiella burnetii has
      been reported to contain an intervening sequence of 444 base pairs (bp). The
      sequence information on the intervening sequence and the 23S rRNA gene was
      exploited to develop a specific PCR-based assay for C. burnetii. A primer set was
      designed that amplified a 477-bp fragment encompassing part of the intervening
      sequence and part of the 23S rDNA. From all of nine C. burnetii strains tested, a
      fragment of the expected size was amplified. As predicted from the published
      sequence, restriction endonuclease digestion of the PCR product from the Coxiella
      strains with RsaI produced two distinct fragments approximately 210- and 270-bp
      in size. The PCR-based method showed a detection limit of 10(2) bacteria as
      determined by visualization of the amplicon on an agarose gel. When
      experimentally infected blood was analyzed, the detection limit was 10(3)
      bacteria. No visible amplicons were observed when 41 bacterial strains,
      representing 29 species other than C. burnetii, were tested. The presence of the
      DNA in all bacterial samples was confirmed by amplification of a 350-bp fragment
      of the 16S rDNA using two universal primers. The described method proved to be
      specific for C. burnetii and may become a rapid and sensitive diagnostic assay
      for C. burnetii. The results also demonstrate that the intervening sequence
      within the 23S rRNA gene is generally found among isolates of C. burnetii.

PMID- 9258534
TI  - Serotyping of Cryptococcus neoformans strains isolated from clinical specimens in
      Thailand and their susceptibility to various antifungal agents.
AB  - One hundred and thirty-nine strains of Cryptococcus neoformans were isolated in
      Thailand from clinical specimens including 97 AIDS patients: 67 from Northern, 48
      from Central, 17 from Northeastern and 7 from Southern regional hospitals. Six
      out of the 139 strains were serotype B and the remaining 133 were A. There was no
      correlation between serotypes and regional distribution. To our knowledge, this
      is the first report of serotyping studies on C. neoformans in Thailand. Studies
      on random amplified polymorphic DNA (RAPD) analysis showed that this method is
      useful for the differentiation of C. neoformans var. gattii (serotypes B and C)
      and C. neoformans var. neoformans (serotypes A and D). They also indicated that
      Thai isolates of C. neoformans var. gattii (serotype B) were a homogeneous group
      on the basis of their genotypes. Antifungal susceptibility tests using 5
      antifungal agents including amphotericin B, fluconazole, flucytosine,
      itraconazole and micronazole against 50 selected strains of C. neoformans showed
      that they were sensitive to all of the antifungal agents tested except for one
      strain that was resistant to flucytosine.

PMID- 9258535
TI  - Mycobacterium malmoense in Italy: the modern Norman invasion?
AB  - The isolation of Mycobacterium malmoense has for a long time been restricted to
      few countries of Northern Europe; reports from countries other than Sweden, Great
      Britain and Finland are rare and the first Italian case report has been published
      in 1995. Since 1988, however, fifteen strains of M. malmoense have been isolated
      in Italy, eleven of which in the last two years; of these, ten appeared
      clinically significant on the basis of medical records. The susceptibility of the
      strains and the role of high performance liquid chromatography of cell wall
      mycolic acids for a reliable identification are discussed.

PMID- 9258536
TI  - Separation of Salmonella typhimurium DT2 and DT135: molecular characterization of
      isolates of avian origin.
AB  - In Denmark, 0.4 and 3.4% of the human Salmonella Typhimurium cases registered
      between 1988 and 1993 were caused by DT2 and DT135, respectively. Separation of
      these two phage types was, however, problematic as only minor differences in
      lysis pattern and lysis strength occurred. Molecular characterization of 23
      Danish isolates, 10 German isolates and the two type strains have subsequently
      been performed. With only minor exceptions, strains examined could be separated
      by combination of 0.5 agglutination, ribotyping, and PFGE typing into two major
      groups in conformity with their phage types. The differences between the two
      groups were, however, very small and it has not been completely clarified whether
      this grouping is the result of two independent types or of two related lines
      developing in different environments. It is concluded that the classification of
      related phage types DT2 and DT135 has to be supported by molecular methods.

PMID- 9258537
TI  - Epidemiology of poisoning due to pharmaceutical products, Poison Control Centre,
      Seville, Spain.
AB  - A retrospective study of telephone calls concerning poisoning due to
      pharmaceutical products, attended by the Toxicological Information Service in
      Seville (Spain), is presented. The years 1993 and 1994 were analized. Demographic
      data including the age and sex of the patient, route of exposure, cause, type of
      poisoning and the therapeutic group, was obtained. The great majority were cases
      of acute poisoning due to domestic accident, attempted suicide took second place.
      Ingestion was the principal route of entry, and more males than females were
      affected. 35.2% were children under two. In general, the medicines most
      frequently involved were those affecting the nervous system (28.1%)--principally
      analgesics, anxiolytics and antidepressants--followed by dermatological agents
      (13.7%)--such as antiseptics and disinfectants-and those affecting the
      respiratory (medicines to treat common cold, bronchodilators, antitussives) and
      digestive systems (laxatives, antiacids). It is hoped that with knowledge of data
      from as many poisons centres as possible, an improvement may gradually be seen in
      the prevention of the such poisoning in the future.

PMID- 9258538
TI  - Epidemiology of carcinoid tumours in central Italy.
AB  - Between 1985 and 1991, 83 carcinoid tumours were diagnosed in the province of
      Florence where the Tuscany Tumour Registry is active. There were 44 males and 39
      females. The age-adjusted incidence was 0.65 cases/100,000 population/year. The
      most common location was the lung (30.1%), followed by colorectum (25.2%) and
      small intestine (22.8%). The 5-year observed and relative survival rates were
      70.8% and 78.9% respectively. The relative risk of developing multiple primary
      cancers was 0.79 (CI 95% 0.28-8.33).

PMID- 9258540
TI  - Fairly elevated incidence of goiter with marginally low urinary iodine in
      adolescents living in the north-western part of Tunisia.
AB  - In order to study the etiology of endemic goiter in the north-western part of
      Tunisia, we examined 93 adolescents of this region. We measured urinary iodine
      concentrations, serum total thyroxine, total triiodothyronine, thyrotropin,
      thyroglobulin and antithyrogobulin antibody concentrations. The adolescents were
      questioned about their alimentary habits, the origin of their drinking water and
      the presence of known goiter(s) in their family. Among these adolescents, 49.5%
      of them had a goiter. Urinary iodine concentrations showed mild iodine
      deficiency. The serum determinations gave results within the reference ranges,
      without any significative differences between adolescents, with or without
      goiter. We found two risk factors: the age of adolescents, and the presence of a
      known goiter in the family. These results suggest that the actual prevention may
      not be adequate, or most likely that goitrogenic factors are to be looked for,
      especially in drinking water, since the majority of these adolescents drink no
      controlled water.

PMID- 9258539
TI  - Endemic level of Lyme borreliosis in a region of central France: a sero
      epidemiologic examination involving blood donors.

PMID- 9258541
TI  - Molecular analysis of an outbreak of influenza in the United Kingdom.
AB  - The first outbreak of influenza virus in Europe in 1995/1996 occurred in a school
      in the south of England. RT-PCR-restriction analysis was performed on the HA1
      portion of influenza haemagglutinin gene amplified directly from clinical
      samples. These were taken at the onset of the outbreak and indicated co
      circulation of two distinct genetic variants of influenza virus which were
      antigenically identical. Investigations of this nature demonstrate the genetic
      diversity of circulating variants of influenza and have the potential to provide
      information on molecular evolution of strains within closed populations.

PMID- 9258542
TI  - Deliveries, abortion and HIV-1 infection in Rome, 1989-1994. The Lazio AIDS
      Collaborative Group.
AB  - The prevalence of HIV-1 among women of reproductive age is currently estimated at
      the time they give birth. We assessed HIV-1 prevalence at the end of pregnancy,
      whether they delivered or had an induced or spontaneous abortion. Women admitted
      at the end of pregnancy to hospitals in the Lazio Region, Italy, were tested for
      antibodies to HIV-1. Consent for testing was granted by 97.1% of 218,357
      subjects; women who did not consent were tested anonymously. The prevalences of
      infection were 0.34% in 1989, 0.38% in 1990, 0.28% in 1991, 0.23% in 1992, 0.28%
      in 1993, and 0.24% in 1994. Significantly higher prevalences of infection were
      associated with induced abortion (0.49%) than with delivery (0.18%; OR: 2.72; 95%
      CI: 2.29-3.22) and among women who refused (0.85%) than among those who consented
      to testing (0.27%; OR: 3.14; 95% CI: 2.35-4.19). A significant temporal reduction
      in prevalence was observed only among women who delivered (0.15% in 1993 and
      1994; 0.26% in 1989 and 1990). The prevalence of HIV-1 infection is thus higher
      among women undergoing induced abortions than among those who deliver and higher
      among women who refuse testing than among those who consent. Studies confined to
      neonatal testing or to voluntary testing of pregnant women would thus
      underestimate the prevalence of HIV-1 among women of reproductive age.

PMID- 9258544
TI  - Percutaneous blood exposure among Danish doctors: exposure mechanisms and
      strategies for prevention.
AB  - The objective of this study was to describe the mechanisms of percutaneous blood
      exposure (PCE) among doctors and discuss rational strategies for prevention. Data
      were obtained as part of a nation-wide questionnaire survey of occupational blood
      exposure among hospital employed doctors in Denmark. The doctors were asked to
      describe their most recent PCE, if any, within the previous 3 months. Detailed
      information on the instruments, procedures, circumstances and mechanisms that
      caused the PCE was obtained. Of 9375 doctors, 6256 (67%) responded, and 6005
      questionnaires were eligible for analysis. Of 971 described PCE the majority were
      caused by suture needles (n = 483), i.v.-catheter-stylets (n = 94), injection
      needles (n = 75), phlebotomy needles (n = 53), scalpels (n = 45), arterial blood
      sample needles (n = 41) and bone fragments (n = 23). Inattentiveness was the most
      common cause, contributing to 30.5% of all PCE. Use of fingers rather than
      instruments was a major cause of injury in surgical specialities and was a
      contributing cause of 36.9% PCE on suture needles. Common contributing causes
      when fingers were used (n = 199) were poor space in (30.2%) or view of (18.6%)
      the operation field. It was often argued that instruments were not practical to
      use or might harm the tissue. Of 689 PCE in surgical specialties, 17.4% were
      inflicted by colleagues. Up to 53.3% of PCE on hollow-bore needles could be
      attributed to unsafe routines like recapping only, but other mechanisms like
      sudden patient movements and 'acute situation' were common, especially in the
      case of PCE on i.v.-catheter-stylets. It is concluded that the exposure
      mechanisms of PCE reflect both unsafe routines, difficult working conditions and
      unsafe devices. Education in safer working routines are needed in all
      specialties. Introduction of safer devices should have a high priority in
      surgical specialties, and should be considered in non-surgical specialties too.

PMID- 9258543
TI  - The inverse relation of average population blood pressure and stroke mortality
      rates in the seven countries study: a paradox.
AB  - This study attempts to explain the unexpected finding of an inverse population
      (ecological) relationship between mean systolic blood pressure levels and stroke
      death rates in 25 years follow-up of the Seven Countries Study, a cross-cultural
      study of cardiovascular disease. Sixteen cohorts of all men aged 40-59 in seven
      countries (one cohort in the USA, two in Finland, one in the Netherlands, three
      in Italy, two in Croatia (former Yugoslavia), three in Serbia (former
      Yugoslavia), two in Greece, two in Japan) were surveyed from 1958 to 1964. Risk
      factors and personal characteristics were measured and follow-up for vital status
      and cause of death was then carried out over 25 years. Analyses were based on
      comparisons of mean levels of risk factors and death rates within and among the
      16 cohorts. Mean entry population levels of systolic blood pressure among the
      cohorts were strongly and inversely related with their 25-year stroke death rates
      (R -0.55; CI -0.81 and -0.06; p = 0.0276). Within cohorts in contrast, the
      individual relation of blood pressure and stroke was strongly positive and
      significant in 14 of the 16 cohorts. Mean population levels of serum cholesterol
      were inversely and strongly related to stroke death rates (R -0.79; CI -0.92 and 
      0.46; p = 0.0003), while the partial correlation coefficient of systolic blood
      pressure, computed in models including serum cholesterol, became small and not
      significant (-0.05; CI -0.55 and +0.48; p = 0.8537). Age at death for stroke
      (average 68.9 +/- 7.1 years) was significantly higher than age at dath from
      myocardial infarction and sudden death (average 65.8 +/- 7.8 years) suggesting a
      competition effect between the conditions. Multivariate models including
      population average systolic blood pressure and serum cholesterol provided no
      added explanation for the lack of direct and significant relationship of
      population blood pressure with stroke death rates. They were based on these
      variables: age at stroke death, age at myocardial infarction death or and sudden
      death, death rates from myocardial infarction and sudden death, the interaction
      term of systolic blood pressure with serum cholesterol and the multivariate
      coefficients for systolic blood pressure from Cox models run in individuals.
      Similar findings were obtained using diastolic instead of systolic blood pressure
      and excluding the Japanese cohorts. The paradox of the inverse ecologic relation
      of population blood pressure and stroke mortality and a direct relation for
      individual is only partly explained by the cofounding effect of population mean
      serum cholesterol levels. An effect of low cholesterol levels on excess stroke
      mortality cannot be excluded. A major limitation of the study was our inability
      to segregate thrombotic from heamorrhagic strokes.

PMID- 9258545
TI  - Effect of maternal lifestyle on cord blood IgE factor.
AB  - During recent decades much interest has been focused on the possibility of
      predicting and preventing atopic diseases during pregnancy. The idea of being
      able to detect a predisposition early and take suitable environmental measures in
      order to avoid overt allergy is an attractive position. Elevated cord IgE of
      around 1.0 IU/ml has been proposed as a predictor in western children. However,
      there remains no information about the effect of maternal lifestyle during
      pregnancy on these levels. Total IgE levels were therefore determined using
      Pharmacia CAP system and PRIST, with sensitivities of 0.01 kU/l and 0.25 kU/l,
      respectively, from serum samples taken from 1138 Japanese pairs of cord blood and
      pregnant women responding to a questionnaire regarding 17 health practices,
      intake of 32 food allergens and 5 environmental factors. Of these, 28 (2.5%)
      pairs of samples were excluded from further analysis because of high
      contamination of IgA (> 15.4 mg/ml) in cord blood. Median cord blood IgE was
      0.286 kU/l and geometric mean IgE was 66.25 kU/l in maternal sera using CAP
      system; there was no significant correlation between maternal log (IgE) and cord
      blood IgE. Similar results were obtained from PRIST, whose correlation with CAP
      system was significant (r = 0.884, p < 0.001 for maternal and r = 0.765, p <
      0.001 for cord blood). Multiple logistic analysis demonstrated that avoidance of
      simultaneous exposure to hens' eggs and cow's milk (relative risk = 1.3, p <
      0.05) as well as soy beans (relative risk = 2.8, p < 0.01) should be advised to
      mothers with positive allergic histories and/or high total IgE (> 400 IU/ml),
      especially in women aged more than 35 years who are pregnant with a male child.
      However, maintenance of healthy lifestyles, especially taking proper exercise and
      sleeping, and avoidance of inhalant allergens during late pregnancy may be a more
      important strategy for the reduction of cord blood IgE levels.

PMID- 9258547
TI  - Prevalence of hepatitis A, B, and C markers in school children of a rural area of
      Crete, Greece.
AB  - OBJECTIVE: To determine the prevalence of hepatitis A, B, and C markers in
      children who were attending junior and senior high schools in a high risk area in
      rural Crete, Greece. METHODS: Three-hundred and thirty-four children who attended
      the three junior schools and one senior high school in the Agios Vassilios
      province of Southern Crete were invited to participate in the study. Three
      hundred and four of them were tested for hepatitis A, B, and C markers. Hepatitis
      B (HBV) markers (HBsAg and anti-HBc) as well as hepatitis A (anti-HAV) and
      hepatitis (anti-HCV) antibodies were tested with commercial enzyme-linked
      immunosorbent assay kits. RESULTS: Six of the 304 children (1.97%) were found to
      be positive for anti-HAV, 1 (0.33%) to HBsAg, 7 (2.30%) to anti-HBc and none were
      found positive for anti-HCV. No significant differences were seen between the
      prevalence of anti-HAV antibodies in males (2%) and females (1.95%), and of anti
      HBc antibodies in males (3.33%) and females (1.30%). CONCLUSIONS: The very low
      prevalence of anti-HAV is obviously due to the improved conditions of hygiene and
      it raises the question of the possible emergence of this disease at an older age
      and therefore appropriate preventative strategies should be considered. The low
      endemicity of hepatitis B in Crete in contrast to other areas of Greece also
      calls for a vaccination policy probably during adolescence. The absence of
      hepatitis C markers in the children in contrast to the observed higher prevalence
      of HCV-infected people in the adult population in the same rural area raises
      questions regarding possible sources of transmission of hepatitis C during the
      preceding years.

PMID- 9258546
TI  - The validity of hospital discharge register data on coronary heart disease in
      Finland.
AB  - We studied the validity of the Finnish hospital discharge register data on
      coronary heart disease (CHD) for the purposes of epidemiologic studies and health
      services research. The Finnish nationwide hospital discharge register (HDR) was
      linked with the FINMONICA acute myocardial infarction (AMI) register for the
      years 1983-1990. The frequency of errors in the HDR was assessed separately.
      Between 8% and 13% of hospitalized AMI events registered in the AMI Register were
      not found in the HDR with an ICD code for CHD. Problems with the register linkage
      and the use of some ICD code other than one of the codes for CHD explained these
      missing events. The frequency of errors in the personal identification number was
      about 5% in the early 1980s. After 1986 errors were found only occasionally. The
      diagnosis recorded in the HDR was the same as that in the discharge sheet in
      about 95% of hospitalizations. The positive predictive value of the ICD code 410
      (AMI), compared with the FINMONICA definite+possible AMI category, was very high
      and stable, about 90% in all areas and all hospitals, but the sensitivity varied
      from 50% at local hospitals to 80% at central hospitals. In summary, data on CHD
      obtained from the Finnish hospital discharge register give, on average, a correct
      picture on changes in the occurrence of AMI in Finland and can, with necessary
      caution, be used in epidemiological studies and health services research.
      However, the classification of individual cases is not standardized in the HDR,
      but varies over time, between geographical areas and the levels of care.
      Therefore, these data should not be used without confirmation in studies where
      correct classification of individual outcomes is of crucial importance, such as
      follow-up studies and case-control studies.

PMID- 9258548
TI  - Awareness, treatment and control of hyperlipidaemia, hypertension and diabetes
      mellitus in a selected population of southern Italy.
AB  - The purpose of the present study was to assess the degree of awareness, treatment
      and control of hyperlipidaemia compared with hypertension and diabetes mellitus
      in a selected population of southern Italy. All participants to a cardiovascular
      disease prevention campaign examined between April 1994 and July 1995 were
      screened for hyperlipidaemia, hypertension and diabetes mellitus. Subjects
      received also ECG, echo-Doppler of carotid arteries and filled in a questionnaire
      concerning personal and familial cardiovascular diseases, smoking habit and drug
      consumption. Of the 742 participants, 327 were found to have hypertension, 73 to
      have diabetes mellitus, 287 to have mild hyperlipidaemia and 322 to have moderate
      severe hyperlipidaemia. Among hypertensive subjects, 60.2% were aware of their
      condition, 53.5% were treated and 15.6% had their blood pressure controlled at
      the recommended level (< 140/90 mmHg). Among diabetic subjects, 76.7% were aware,
      64.4% treated and 19.2% reached fasting blood glucose level of less than 7.77
      mmol/l (140 mg/dl). Only 24.0% of subjects with mild hyperlipidaemia were aware
      of their condition. Of the subjects found to have moderate-severe
      hyperlipidaemia, 64.9% were aware, 32.3% were treated and 9.0% had plasma
      cholesterol and triglycerides concentration of less than 6.45 and 5.65 mmol/l
      (250 and 500 mg/dl), respectively (cutoffs chosen to separate mild from moderate
      severe hyperlipidaemia). These results show that mild hyperlipidaemia is almost
      neglected whereas awareness of moderave-severe hyperlipidaemia is quite
      widespread and comparable to that of hypertension and diabetes mellitus.
      Prevalence of treatment and control of moderate-severe hyperlipidaemia is,
      however, much lower than that of hypertension and diabetes.

PMID- 9258550
TI  - First epidemiological data on pathogenic leptospires isolated on the Azorean
      islands.
AB  - Insectivores (Erinaceus europaeus) and rodents (Rattus rattus, R. norvegicus and
      Mus musculus) from different islands of the Azores Archipelago were found to
      carry three distinct Leptospira interrogans s.l. serovars (copenhageni,
      icterohaemorrhagiae and ballum) which have never been previously investigated
      there. The house mouse and the black rat were the major Leptospira reservoirs
      showing isolation rates ranging from 0% for both species (in Graciosa) to 88% and
      33%, respectively (in Saao Miguel). This study also showed that the majority of
      the animals with positive kidney cultures exhibited specific agglutinins against
      the isolated strains of Leptospira. The observed isolation rates in the different
      islands, with a very interesting island variation in prevalence, suggest that
      small mammals, serving as sylvatic reservoirs of pathogenic leptospires, may
      represent an important risk to the health of humans and livestock, particularly
      in the islands of Terceira and Saao Miguel.

PMID- 9258551
TI  - Risk infection factors in the total hip replacement.
AB  - Infection is a complication that occurs in a considerable percentage of hip
      prostheses replacements, being in many cases necessary to retire them, which
      generates important health and economical problems. OBJECTIVES: To know the
      distribution of infection and its risk factors in total hip replacement. MATERIAL
      AND METHODS: A four year prospective study was developed in the rehabilitation
      and orthopedic center of 'La Paz' Hospital. A total of 873 patients were
      included. Patients were controlled by means of active epidemiological
      surveillance until the day of discharge, listing up their characteristics at
      admission and risk factors during their stay. A multivariant study was carried
      out to determine risk factors. RESULTS: Patients' average age was 63 years, 3.4%
      of them suffered from diabetes and there were no inmunocompromised patients. The
      percentage of wound infection during the four years was 6%, being reduced to 1.2%
      in the last year. The risk factors found in the multivariant study were:
      incorrect prophylaxis (OR: 3.85), wrong scaring (OR: 14.06), suffering more than
      one intervention (OR: 7.31) and a hospitalization period longer than 30 days (OR:
      2.84). CONCLUSION: We think that special attention in the care of the surgical
      wound, as well as the correct use of prophylaxis, can significantly collaborate
      to the reduction of infection.

PMID- 9258549
TI  - Impacts of components of the metabolic syndrome on health status and survival in
      an aged population.
AB  - The clinical significances of different components of the multiple metabolic
      syndrome were studied in a five-year follow-up study of random persons (n =
      1,199) of four birth cohorts at ages 65, 75, 80, and 85 years. The subjects were
      examined clinically and their serum lipids, blood glucose, plasma insulin, blood
      pressure, and health score were determined. The health score was measured using a
      visual analogue scale. All subjects were followed for 5 years. Health score,
      diastolic blood pressure and body mass index declined over age, but serum
      triglycerides, and blood glucose were similar, whilst serum high density
      lipoprotein (HDL)-cholesterol increased. Among women fasting plasma insulin was
      lowest in the age group of 65 years. The associations of components of the
      multiple metabolic syndrome varied by age. In the age groups of 65 and 75 years
      high body mass index, plasma insulin, glucose, triglycerides and low HDL
      cholesterol were associated with impaired health. In the age group of 85 years
      high blood pressure, total cholesterol, and HDL-cholesterol were associated with
      good health. The baseline health score was consistently lower in the decedents
      than survivors of all age groups, but components of the metabolic syndrome were
      generally not associated with impaired survival.

PMID- 9258552
TI  - Prevalence and antifungal susceptibility of vaginal yeasts in outpatients
      attending a gynecological center in Ancona, Italy.
AB  - Between February 1993 and May 1994 we studied the prevalence of fungal
      vulvovaginitis among women attending the Obstetric and Gynecology Clinic of the
      University of Ancona. Out of the 222 patients, 18 (8.2%) women had symptomatic
      vaginitis and 24 (10.8%) were carriers. Candida albicans was the species most
      frequently isolated (44.2%), followed by Torulopsis glabrata (28%) and
      Saccharomyces cerevisiae (16.2%), from symptomatic and carrier patients. The
      activity of acid proteinase was determined for C. albicans isolated from both
      symptomatic and carrier patients. All 13 carriers showed low activity for
      aspartyl proteinase (score 1+), while 5 of 6 symptomatic patients showed higher
      activity (score 2+), with a significant difference (p = 0.026). In general,
      isolates of T. glabrata and S. cerevisiae were less susceptible in vitro to
      fluconazole than isolates of C. albicans. We did not find any differences in
      fluconazole MIC results among the C. albicans strains isolated from symptomatic
      and carrier patients. On the other hand, the fluconazole MICs of T. glabrata and
      S. cerevisiae isolates showed statistically significant differences between
      symptomatic and carrier patients (p = 0.009 and p = 0.000, respectively). The
      differences in proteinase secretion between the isolates from symptomatic and
      carrier patients suggest a correlation between proteinase production and vaginal
      candidiasis caused by C. albicans. Torulopsis glabrata, however, was found to be
      the most common causative agent of vaginitis (7 out 19 episodes), followed by C.
      albicans (6 out of 19 episodes). Due to the varying patterns of antifungal
      susceptibility, mainly to fluconazole for the yeast isolates considered in this
      study, an in vitro susceptibility testing program might be useful for monitoring
      the outcome of this infection.

PMID- 9258553
TI  - Lipid, protein, and calorie content of different Atlantic and Mediterranean fish,
      shellfish, and molluscs commonly eaten in the south of Spain.
AB  - We undertook a systematic evaluation of the lipid, protein, calorie, and fatty
      acid composition in 35 species of fish, shellfish and molluscs commonly consumed
      throughout the four seasons of the year in Andalusia, Spain. Using a portion of
      muscle tissue the following were measured in each study unit: total lipids
      (extraction using Folch's method and gravimetry), protein concentration
      (Kjehldal's method), total calories (direct calorimetry), and composition of
      fatty acids (gas chromatography). The lipid, protein, and different fatty acid
      concentrations found are presented in table form. There was a high degree of
      inter-species variability in the concentration of lipids and the various fatty
      acids. There was also a high degree of intra-species seasonal variability in some
      cases. The relative proportion of fatty acids was not independent of the total
      concentration of lipids, independently of the season studied. This systematic
      study of a large group of species shows that the cataloguing of fish as 'white'
      or 'blue' depends especially on the time of year they are captured. For example,
      in spring the mackerel (Scomber scombrus), a fish considered traditionally to be
      'blue' (fatty), has the same lipid concentration as the dover sole (Solea
      vulgaris), commonly considered to be 'white' (little fat), and the sea pike
      (Merluccius merluccius) has a higher lipid concentration in autumn than the jack
      mackerel (Trachurus trachurus). Even greater differences existed when the fish
      were classified according to their richness in n-3 fatty acids. These differences
      in the total lipid concentration and the composition of fatty acids, as well as
      the inter-relations between them, may, under certain circumstances, be important
      for the calculation of dietary calories and nutritional values, and may explain
      the differences found between the various tables of food composition, as well as
      the divergent results in epidemiological studies on the association between fish
      in diets and various diseases, such as diabetes or ischaemic cardiopathy.

PMID- 9258554
TI  - Epidemiological features of complicated UTI in a district hospital of Kuwait.
AB  - Records from patients admitted to the surgical or medical department or examined
      in the respective outpatient departments in a Kuwaiti district hospital were
      reviewed retrospectively to discern the demographic characteristics of patients
      with complicated urinary tract infections (UTI), underlying conditions, pathogens
      and their antimicrobial susceptibility patterns. Kuwaiti nationals constituted
      the largest group, followed by Egyptians, which in the population of 225 patients
      studied comprised 41% and 27%, respectively; 65 of these 225 patients (29%) had
      urinary stones; 33 of the 92 Kuwaiti patients (36%) had diabetes mellitus; 38 of
      the 60 Egyptian patients (63%) had urinary stones and 18 had bilharziasis (30%).
      Pathogens were isolated 353 times from 225 patients. Escherichia coli, Klebsiella
      pneumoniae, Pseudomonas aeruginosa and several other organisms in those patients
      with bilharziasis, urinary stones, and especially diabetes mellitus, displayed
      lower susceptibility frequencies to antimicrobials in comparison with other
      surgical and medical UTI isolates. Surgical and medical UTI organisms showed an
      overall higher antimicrobial resistance frequency than did UTI organisms from the
      maternity department or regional clinics. More than half of the population of
      Kuwaiti consists of expatriates from different countries. Such a population
      structure can exhibit peculiarities when health is considered. All this should be
      taken into consideration while dealing with disease management.

PMID- 9258555
TI  - Study of the 16S-23S ribosomal DNA internal spacer of Coxiella burnetii.
AB  - The complete 16S-23S ribosomal DNA (rDNA) internal transcribed spacer (ITS) of 22
      isolates of the obligate intracellular bacterium Coxiella burnetii, the agent of
      Q fever, were amplified by the polymerase chain reaction (PCR) and sequenced
      using an automated laser fluorescent DNA sequencer. The ITS measured 497 base
      pairs (bp) and encoded isoleucine-tRNA and alanine-tRNA. The comparison of the
      sequence alignments of the 22 C. burnetii strains revealed very high levels of
      sequence similitary (> 99%) although they had different geographic origins and
      phenotypic characteristics. Sequencing of the 16S-23S rDNA ITS of C. burnetii
      could be utilized for identification of the bacterium but is not applicable to
      studies of epidemiology, virulence and taxonomy.

PMID- 9258556
TI  - Exposure of cats in southern Africa to Coxiella burnetii, the agent of Q fever.
AB  - Recently, the domestic cat has been implicated in numerous outbreaks of Q fever
      in humans. To determine if cats in southern Africa are infected with the agent of
      Q fever we tested sera from cats in South Africa and Zimbabwe by indirect
      fluorescence for antibodies reactive with phase II Coxiella burnetii antigen
      (Nine Mile strain). Reactive antibodies were detected at titres of > or = 1/40 in
      sera from cats in South Africa (1/52, 2%) and Zimbabwe (15/119, 13%). Our results
      indicate that cats in southern Africa are infected with C. burnetii and should be
      considered as sources of infection for humans.

PMID- 9258557
TI  - Prevalence of hepatitis A antibodies in southeastern Spain: a population-based
      study.
AB  - The prevalence of hepatitis A antibodies in the adult population of the Murcia
      Region (southeast of Spain) was estimated using an anonymous unlinked serosurvey
      in a population-based sample of 2,203 adults. The overall anti-HAV prevalence was
      76.5%. The prevalence increased with age and was higher in individuals living in
      towns with less than 10,000 inhabitants.

PMID- 9258558
TI  - Giardiasis in HIV: a possible role in patients with severe immune deficiency.
AB  - We report the epidemiological, clinical and therapeutic characteristics of
      giardiasis in a population of HIV-infected patients with diarrhoic syndrome.
      During the period between 1988 and 1995, 720 HIV-patients with diarrhoic syndrome
      were evaluated. Fecal specimens were submitted to parasitological examination
      according to the Ritchie formalin-ethil acetate centrifugal sedimentation method
      and stained with iodine. Samples also underwent modified Ziehl-Neelsen staining
      and standard bacteriologic testing. Cystis of G. intestinalis were identified in
      stool sample of 25 patients. Two patients were classified as in stage A2 and 23
      in C3. Mean CD4 values of patients with giardiasis (26.9 cells/mmc) were compared
      with those of 65 patients from whom, during the study, was isolated
      Cryptosporidium parvum (63.12, cells/mmc): the difference resulted highly
      significant (p < 0.001). Among the patients with full-blown AIDS, giardiasis
      occurred following a single previous AIDS-defining event in 13 inividuals, in
      seven and in five subjects giardiasis was the 3rd and, respectively, the 4th
      relevant AIDS-defining condition. Death occurred within the following 2 months in
      nine patients and within 6, 12 and 24 months in seven, six and two patients,
      respectively; at present only three AIDS patients are still alive. In general, G.
      intestinalis in HIV+, is not considered a major cause of enteritis; nevertheless,
      in our experience enteritis due to G intestinalis is a frequent event among AIDS
      patients, especially in the most advanced stage of disease, irrespectively of the
      risk factor. The increase in mean survival of AIDS patients will probably lead to
      a progressive emergence of this pathogen which could determine a severe diarroic
      syndrome with hydro-electrolytic impairments.

PMID- 9258559
TI  - Classification of heart failure in population based research: an assessment of
      six heart failure scores.
AB  - Several scores based on symptoms and signs have been developed to assess the
      presence of heart failure. The goal of this study was to compare six heart
      failure scores in non-hospitalised subjects and to determine their usefulness in
      population based research. The scores were applied to 54 participants of a
      population based study. All underwent a complete medical examination, including
      chest X-ray, electrocardiography and Doppler echocardiography. Using all
      information available, a cardiologist, unaware of the results of the scores,
      clinically classified participants as having no, possible or definite heart
      failure. Sensitivity, specificity, predictive values and receiver operating
      characteristics were calculated, using the cardiologist's assessment as a gold
      standard. The cardiologist judged definite or possible heart failure to be
      present in 17 persons. All scores had a high sensitivity for the detection of
      definite heart failure, whereas the study of men born in 1913 and Walma's score
      had the highest sensitivity for the combination of possible and definite heart
      failure. Gheorgiade's and the Boston score had the highest positive predictive
      values. In conclusion, five of the six scores we studied are broadly similar in
      the detection of heart failure. The men born in 1913 score relies heavily on the
      assessment of dyspnea, resulting in a relatively large number of false positives.
      Although the scores are useful in detecting manifest heart failure, objective
      measurements of cardiac function appear necessary to reduce the false positive
      rate and accurately detect early stages of heart failure.

PMID- 9258560
TI  - Israeli women were at a higher risk than men for mortality following coronary
      bypass surgery.
AB  - As part of a national study of surgical departments is Israel, cardiac surgery
      patients undergoing open heart surgery between 1987 and 1989 were followed-up
      prospectively. Of these, 1,046 patients had coronary artery bypass grafting
      (CABG) and are the subject of this report. The six-months mortality after surgery
      was 12.9% among 202 women and 4.1% among 844 men. Female gender was an
      independent predictor of mortality even after controlling for the effect of 14
      putative risk factors. The adjusted relative risk for mortality in women compared
      to men was 2.79 (1.5-5.2). In an attempt to understand this excessive mortality
      among women, a detailed analysis in one of the participating hospitals revealed
      differences associated with surgical technique by gender, such as proportion of
      patients with entirely venous grafting vs internal mammary artery grafts (IMA).
      Thirty percent of women vs 4.8% of men had entirely venous grafting. Adjusting
      the data for differences in the proportion of venous grafting has obliterated the
      difference in mortality between the genders in that hospital. We suggest that
      interventions to reduce mortality among women should involve a more careful
      choice of female candidates for CABG surgery, as well as introduction of
      modifications in the operating technique.

PMID- 9258562
TI  - The prevalence of HCV infection in a cohort of pregnant women, the related risk
      factors and the possibility of vertical transmission.
AB  - The prevalence of antibodies for one or more HCV antigens was 2.3% of 1,347
      mothers at childbirth. Compared with the principal factors studied, the presence
      of antibodies was more frequent in women who were carriers of HIV infection
      (3/3), in those who had suffered liver diseases (5/37) or who had had transfusion
      (3/25). This was as opposed to women who did not have any risk factor (p <
      0.001). The prevalence of HCV-RNA was 1.3%; in relation to the antibody state,
      such a condition was more frequent in subjects with antibodies for 3 or 4
      antigens (about 80%) compared with those who were positive for 1 or 2 antigens.
      HCV-RNA of the same genotype as the mother (type 1; 1a) was also found in the
      funicular blood of 2 of the 18 babies born to mothers who were positive for HCV
      RNA. In the course of the follow-up (from the 3rd to the 18th month) the viral
      RNA was not found in any of the babies, nor was it found in the 2 who were
      positive at birth. Even the antibodies gradually disappeared, although slowly. At
      the 10th month, 91% of the babies resulted as having no antibodies and at the
      18th month none of the babies resulted as having antibodies. Breast-feeding also
      appeared to have no influence on the transmission of the infection; out of 18
      viremic mothers indeed 12 (67%) breast-fed their babies.

PMID- 9258563
TI  - Epidemiological characteristics of gastric cancer in Vojvodina.
AB  - Epidemiological characteristics of gastric cancer in the province of Vojvodina
      were analyzed on the basis of official data of the Cancer Registry of Vojvodina
      and the records of the Bureau of Census of Vojvodina for the years 1982-1991. In
      the year 1991, the cases of gastric cancer accounted for 7.8% of all malignant
      neoplasms in males, ranking thus third, whereas in females, with 5%, it was in
      seventh place. At the same time, in the structure of deaths from malignant
      neoplasms, gastric cancer was on the second place both in males (9.1%) and
      females (7.8%). The male/female gastric cancer mortality ratio was 1.7:1.
      Incidence and mortality rates showed the tendency of a slow but steady decrease
      in both sexes during the observation period. The age-standardized incidence rate
      (world population) was 25.9 per 100,000 for men and 9.4 for women in average. In
      comparison with the corresponding data of the registries of Europe and of the
      world, Vojvodina falls in the range of moderately high rates. The age-specific
      incidence and mortality rates show a strong increase after the age of 55,
      reaching the highest values in the ages 75-79. Thus it can be said that gastric
      cancer is a disease of the elderly. Total five-year survival is low, which is a
      common observation for this kind of neoplasm.

PMID- 9258561
TI  - Prevalence of hepatitis C virus infection in Nanjing, southern China.
AB  - There is little information on the prevalence of hepatitis C virus (HCV)
      infection in China. The prevalence of HCV infection was determined in 998
      subjects (398 with liver disease and 600 without) in the city of Nanjing in
      southern China. Subjects were tested for anti-HCV antibodies by a second
      generation assay. We also determined serological HCV genotypes and HCV RNA
      sequences. Among the 600 subjects without liver disease, 3 (0.5%) were
      seroreactive for anti-HCV. All were less than 12 years of age and had a history
      of transfusion. Of the 398 liver disease patients, 20 (5.0%) were seroreactive
      for anti-HCV. Of 16 patients in whom serological HCV genotype was determined, 10
      (62.5%) were infected with HCV type 1, 5 (31.3%) with type 2 and 1 (6.3%)
      undetermined. HCV genomes sequenced from 2 patients belonged to genotype 2 and
      were closely related to strains in Beijing and Japan by molecular evolutionary
      analysis. These results suggest that HCV infection is rare and not a major cause
      of liver disease in southern China.

PMID- 9258564
TI  - Diphtheria: epidemiological update and review of prevention and control
      strategies.
AB  - The importance of anti-diphtheria immunity in adults through periodic booster
      doses of vaccine is now increasing after last years diphtheria outbreaks in Newly
      Independent States (NIS) and Algeria and a few cases found in Europe and USA.
      Diphtheria cases notified in Italy between 1991-1994 have been reported. In 1995
      WHO outlined the need to review vaccination schedules against diphtheria in all
      countries where gaps occur in the immunity of adults. The main sero
      epidemiological studies performed in adults and vaccination schedules against
      diphtheria in some industrialized countries have been examined. Actual situation
      and control strategies adopted by WHO in the NIS and implications for other
      countries have been briefly presented. Finally, guidelines for management,
      investigation and control of diphtheria have been reported, including CDCs
      recommendations.

PMID- 9258566
TI  - Parental reporting of childrens' coughing is biased.
AB  - Assessment of cough in the clinical setting as well as in community-based studies
      of respiratory epidemiology has relied on self-reports. To examine the accuracy
      and potential for systematic bias in reported cough during a field study,
      questionnaires administered to parents about their childrens' coughing were
      compared to overnight cough recordings performed in 145 homes in the community of
      Wallaceburg, Canada. Percentage agreement between reported and recorded coughing
      was low, with kappa statistics ranging from 0.02-0.10. Compared to non-smoking
      parents, smokers under-reported their childrens' coughing (p = 0.01). The
      association found between parental smoking and recorded coughing was biased
      towards the null when reported coughing was substituted for recorded coughing:
      the odds ratio between parental smoking and recorded coughing was 3.1 (95% CI:
      1.1-8.8) whereas for reported coughing it was 0.6 (95% CI: 0.2-1.7), the
      difference in the odds ratios being significant at p = 0.03. When carrying out
      field surveys, consideration should be given to measuring cough in a subsample of
      the population in order to estimate the degree of bias inherent in the
      questionnaire-based results.

PMID- 9258565
TI  - Serological survey on the immunity to diphtheria of the northern Greek
      population.
AB  - The recent outbreak of diphtheria in the Newly Independent States (NIS) of the
      former USSR and the immigration from these high risk areas to Greece prompted us
      to determine the diphtheria antitoxin levels by enzyme-linked immunosorbent
      assays (ELISA) in 509 healthy individuals (307 males and 202 females) from
      northern Greece. The population under study was divided in ten age groups from 1
      day to > 60 years old. Diphtheria antitoxin levels of > or = 0.1 IU/ml were
      considered as protective ones. 44.6% of the examined people were found
      susceptible. The children up to their twenties seem to be immune to diphtheria in
      a high proportion (86-88.4%). The diphtheria antitoxin levels declined sharply
      above this age (17.6% in the age group 21-30 years old). The level of protection
      in adults appeared to be higher in the oldest group (49%). According to these
      results, the adults are not properly protected. Booster doses of vaccine for them
      are recommended to improve the resistance of the northern Greek population from
      possible infection by toxigenic stains of Corynebacterium diphtheriae, imported
      or endogenous.

PMID- 9258567
TI  - The association of respiratory problems in a community sample with self-reported
      chemical intolerance.
AB  - This epidemiological study evaluated respiratory histories in those individuals
      reporting chemical intolerance (CI) in a community population sample. The
      subsample of 181 completed standard Respiratory Health Questionnaires. CI was
      determined from self-ratings of feeling 'moderately' to 'severely' ill from
      exposure to at least three of five common chemicals (paint, pesticides, car
      exhaust, new carpet, and perfume); the prevalence rate was 22.7%. The comparison
      group (CN) (31.5% of the sample) were selected from their reports of 'never'
      feeling ill from the same chemicals. The prevalence rate of CI in females was
      over twice that in males (28% vs 12.9%), a significant difference. There were no
      significant differences in smoking, age, or education between CI and CN.
      Prevalence rates for symptoms and Relative Risk Ratios (RR) indicated that the CI
      were significantly more likely to report chronic cough, phlegm, wheeze, chest
      tightness, exertional dyspnea, acute respiratory illnesses, hay fever, child
      respiratory trouble, and physician confirmed asthma. Several of these respiratory
      symptoms were significantly, though differentially, related to 'current' asthma
      and hay fever reports. Results suggest a potential vulnerability to and greater
      interference from respiratory illness for the CI, which have implications for
      women's health and quality of life.

PMID- 9258569
TI  - Antipoliomyelitis neutralizing antibodies in maternal and neonatal serum.
AB  - During 1993 blood samples were taken from 1251 women consecutively admitted to
      the Maternity Ward of the University of Parma. Samples were also taken from all
      the newborn babies. Absence of antipolio neutralizing antibodies in serum diluted
      1/2 was shown in 6 mothers; 4 mothers for polio 1, 1 mother for polio 2 and 1
      simultaneously for the poliovirus 1 and 3. If one considers only the cases of
      absence in undiluted serum, there were 2 negative subjects (0.16%). One of these
      was for antibodies against polio 1 and the other for antibodies against polio 2.
      In the cord blood samples the frequency of negative results in serum diluted 1/2
      is higher: 42 in all with 13 babies negative for polio 1. 17 babies for polio 2,
      8 for polio 3 and 2 babies simultaneously for polio 1 and polio 3. If one
      considers just the babies without antibodies even in undiluted serum, the
      fraction of seronegatives is 9 (0.7%) with 1 for polio 1, 6 for polio 2 and 1 for
      types 1 and 3. The Geometric Mean Titres of the antibodies are significantly
      higher in mothers born before 1964 (year of introduction of mass vaccination with
      OPV) compared with those born after that year. Likewise, the same phenomenon was
      observed in the respective children.

PMID- 9258568
TI  - Cigarette smoking, sex hormones and bone density in women.
AB  - It is known that among women over the age of 65, bone mineral density is lower,
      and the risk of hip fracture higher, in smokers than non-smokers. We report a
      study in 1334 health pre- and post-menopausal women aged 35-64 years, to
      determine whether this effect can be attributed to lower oestrogen levels in
      smokers. Among 676 premenopausal women forearm bone density was no lower in
      smokers (95% confidence interval 1% lower, 4% higher). Among 543 postmenopausal
      women who had not used hormone replacement therapy (HRT) for more than a year
      there was no statistically significant difference, but the lower confidence
      interval was consistent with a lower bone density in older smokers (by 8% at age
      55-59, 16% at age 60-64). Measurements in 194 postmenopausal women not taking HRT
      showed that oestrone and oestradiol were similar in smokers and non-smokers, as
      were cortisol and FSH, LH and prolactin. Meta-analysis of the present study and
      previous studies confirmed significantly higher levels in smokers of the
      androgens DHEAS (by 37%) and androstenedione (by 34%). Oestrogens were no lower
      in smokers, and the lower confidence limit excluded more than a trivial effect of
      smoking in lowering oestrogen. These results indicate that the recognised lower
      bone density in elderly smokers cannot be explained by an effect of smoking on
      oestrogen, since in premenopausal women bone density is no lower in smokers and
      in postmenopausal women oestrogens are no lower in smokers. The data suggest a
      balance between higher androgen levels but lower rates of conversion of androgens
      to oestrogens in smokers. The effect of smoking on bone may be due to impaired
      response of bone and other target organs to oestrogen, or to actions independent
      of oestrogen.

PMID- 9258570
TI  - Gestational and neonatal toxoplasmosis: regional seroprevalence in the United
      Arab Emirates.
AB  - Paired maternal/cord blood samples were tested for anti-Toxoplasma IgG or IgM
      antibodies using Biomerieux Micro-EIA2 IgG and IgM test kits. Of the 1503 women
      tested at the time of delivery, 344 (22.9%) were IgG seropositive. Three hundred
      and one maternal sera, including 265 that were IgG positive, were tested for IgM
      antibodies: 47 were found positive, indicating a gestational toxoplasmosis
      incidence of 31 per 1000 pregnancies over one year. All but one of the IgM
      positive maternal sera had tested IgG positive. Cord blood IgG seropositivity was
      similar to the maternal rate but 18 of the 301 babies had significant levels of
      anti-Toxoplasma IgM antibodies. As these 18 babies were all born to mothers also
      positive for IgM antibodies, the calculated rate of transplacental transmission
      was 38.3% with the estimated prevalence of congenital toxoplasmosis of 12 per
      1000 live births. There was no statistically significant positive correlation
      between maternal seroprevalence and such well-known risk factors as consumption
      of raw meat and milk, or proximity of cats and other animals. One baby was born
      with the classical stigmata of congenital toxoplasmosis.

PMID- 9258571
TI  - Epidemiological surveillance of tick populations: a model to predict the
      colonization success of Ixodes ricinus (Acari:Ixodidae).
AB  - A model that predicts the habitat availability for permanent populations of the
      tick Ixodes ricinus has been developed and applied to Spain. The model is based
      on the fuzzy logic rules and has a spatial resolution of about 4 km. Six long
      term climate variables, which cover temperature and rainfall factors, drive the
      model by assigning the expected probability to find stable tick populations.
      Because the high accuracy of this inference tool, it could be used to map
      favourable sites for this tick in the epidemiological lookout of the Ixodes
      ricinus borne diseases.

PMID- 9258572
TI  - A seroepidemiological study of Mycoplasma pneumoniae infections in Denmark over
      the 50-year period 1946-1995.
AB  - The epidemiological pattern of Mycoplasma pneumoniae infections in Denmark over
      the 50-year period 1946-1995 is described. The study is based on blood specimens
      received at the central laboratory at Statens Serum Institut for titration of
      cold agglutinins (CA), initially for the diagnosis of CA positive primary
      atypical pneumonia, and during the 1960s of M. pneumoniae infection; in addition,
      specimens from the last 38 years were tested for antibodies specific to M.
      pneumoniae. By retrospective analysis of the test results compiled over the years
      it was found that intervals of regular periodicity have been interrupted by an
      era of changes in the pattern. Attention is paid to the significance of CA for
      this study, and the possible background of the epidemiological pattern is
      described.

PMID- 9258573
TI  - Pulmonary alveolar microlithiasis: review of Italian reports.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology,
      characterized by the presence of calcific concretions in the alveolar spaces. A
      familial occurrence is frequently found so that an inherited trait is thought to
      be involved. The chest X-ray is characterized by a 'sandstrom' picture while the
      clinical state undergoes to a slow and progressive impairment resulting in
      respiratory failure at the end stage. We have reviewed the Italian literature of
      the past 50 years detecting 48 case-reports of PAM (19 males and 29 females).
      Only 20 out of them were documented in international journals. A familial
      occurrence of 43.7% was found and 18 patients were under age fifteen. There was a
      prevalence in the female sex (60.4%) and in the second decade of life. Chest X
      ray was the most important tool to diagnose PAM revealing the characteristic
      picture in all patient. Bronchoalveolar lavage (BAL) and open lung biopsy
      respectively show the characteristic calcospherites in the recovered fluid (BALF)
      and in the alveolar spaces. About 300 cases of PAM are reported in the
      international literature. We believe these data are probably underestimated
      because many case-reports are not published in international literature.

PMID- 9258574
TI  - Cold-adapted live attenuated influenza vaccines developed in Russia: can they
      contribute to meeting the needs for influenza control in other countries?
AB  - It is now more than 30 years since the first cold-adapted influenza viruses were
      developed in Russia as potential live, attenuated vaccines. In the past 15-20
      years considerable experience has been gained from Russian and joint Russian-US
      laboratory and clinical studies with type A monovalent and bivalent vaccines
      prepared with genetic reassortant viruses derived from one of these cold-adapted
      viruses in particular. A/Leningrad/134/57. More recent experiences include use of
      trivalent cold-adapted vaccines with a type B component. The overall high level
      of safety of individual and combined vaccines in pre-school and school-aged
      children, with illness reductions in open field trials equivalent to that seen
      with inactivated vaccines, is such as to suggest that practical measures might
      now be justified to facilitate expansion of the use of these vaccines to other
      countries. It is proposed that further experimentation with the Russian cold
      adapted live attenuated vaccines should be focused on issues that will relate to
      the public health perspective, i.e. selection of the single best candidate type A
      and B vaccines for intense study using as criteria their potential for meeting
      licensing requirements outside Russia, and documenting the clinical protective
      efficacy of a single vaccine dose compared to two doses as studied until now.
      Resolution of these issues is important to ensure that costs for future live
      vaccine production, control, and utilization will be kept at lowest levels so
      that expanded use of live vaccines will have maximum cost-benefit and afford
      ability. To guide those interested in these issues, examples are given of
      populations for whom a licensed live cold-adapted vaccine might be considered,
      together with indications of extra data needed to fully validate each suggested
      use.

PMID- 9258575
TI  - Risk factors for cardiovascular disease in Canadians of South Asian and European
      origin: a pilot study of the Study of Heart Assessment and Risk in Ethnic Groups
      (SHARE).
AB  - OBJECTIVE: To test the feasibility of recruitment strategies and a 2-hour
      cardiovascular (CV) health assessment (including laboratory tests and
      questionnaires) in preparation for a national, population-based study to
      determine CV risk factors among Canadians of different ethnic origins. DESIGN:
      Cross-sectional study of people of South Asian and European origin from Hamilton,
      Ont., identified by community-based stratified random sampling. SETTING:
      University-affiliated research clinic in Hamilton, Ont. PARTICIPANTS: Thirty-one
      Canadians of South Asian origin and 20 Canadians of European origin 35 to 75
      years of age. INTERVENTIONS: Subjects attended a clinic at which they completed a
      health questionnaire, provided fasting and postprandial blood samples, and
      underwent B-mode carotid ultrasonographic examination as well as anthropometric,
      nutritional and psychosocial assessments. RESULTS: The participants of South
      Asian origin had lived in Canada for 18 years, on average, compared with 48 years
      for those of European origin. More participants of South Asian origin were
      married than those of European origin, and fewer smoked or consumed alcohol.
      Participants of South Asian origin were more likely to have some university
      education. The prevalence of impaired glucose tolerance was 34.5% in the
      participants of South Asian origin and 9.5% in those of European origin (p <
      0.04). The total cholesterol to high-density lipoprotein ratio was elevated in
      the participants of South Asian origin (5.1), compared with those of European
      origin (4.2) (p < 0.05), as was the lipoprotein (a) concentration (log
      transformed) (5.5 v. 4.6 mg/dL, p < 0.02). CONCLUSIONS: This pilot study revealed
      intriguing lifestyle and metabolic differences between participants of South
      Asian and European origin. Those of South Asian origin had a higher prevalence of
      impaired glucose tolerance, dyslipidemia and elevated lipoprotein (a)
      concentrations-factors thought to be associated with premature CVD in this group.

PMID- 9258576
TI  - Effect of progesterone therapy on arginine vasopressin and atrial natriuretic
      factor in premenstrual syndrome.
AB  - OBJECTIVES: To explore the possible role of natriuretic peptides and vasopressin
      in luteal phase fluid retention in premenstrual syndrome (PMS) and to determine
      the effect of progesterone therapy on these hormones. DESIGN: Self-controlled
      prospective study. SETTING: University-based medical research centre. PATIENTS:
      Six patients with PMS were studied during the symptomatic luteal and asymptomatic
      follicular phases. The follicular phase response was used as the control for each
      subject. INTERVENTIONS: An intravenous infusion of 3% saline solution was
      administered on an early follicular and a late luteal phase day in 2 menstrual
      cycles. Progesterone was administered orally during the second luteal phase.
      OUTCOME MEASURES: Osmolality, arginine vasopressin (AVP), atrial natriuretic
      factor (ANF), and brain natriuretic peptide (BNP) levels in plasma, osmolality,
      sodium, potassium, cyclic adenosine monophosphate (cAMP) and cyclic guanosine 5'
      phosphate (cGMP) concentrations in urine, and thirst sensation. RESULTS: Mean
      basal plasma ANF and osmolality levels and the threshold for AVP release and
      thirst were lower, and mean urinary cyclic nucleotide levels and AVP sensitivity
      (amount of AVP secreted per unit rise in plasma osmolality) were higher, in the
      luteal phase than in the follicular phase. With saline loading, there was an
      increase in plasma osmolality, AVP and ANF and in urinary sodium and cyclic
      nucleotide levels. Plasma ANF and osmolality levels remained lower in the luteal
      phase compared with the follicular phase, but AVP levels at the end of the saline
      infusion were higher in the luteal phase than in the follicular phase.
      Progesterone therapy caused an increase in plasma ANF and osmolality levels and
      the AVP threshold and a decrease in AVP levels and sensitivity and urinary cyclic
      nucleotide levels. BNP levels did not change with phase or treatment. The
      differences in AVP threshold with phase and treatment were statistically
      significant (p < 0.001). There was a significant phase effect for plasma ANF (p =
      0.02) and a significant or near-significant interaction effect of phase and
      treatment for plasma ANF (p = 0.06) and urinary cAMP (p = 0.047) and cGMP (p =
      0.066). The effect of phase and treatment was not significant for the other
      measurements. CONCLUSIONS: Luteal phase fluid retention may be due to a relative
      deficiency of ANF and a lower threshold for AVP release. The symptomatic
      improvement produced by progesterone treatment may be due to its stimulation of
      ANF and inhibition of AVP release or synthesis.

PMID- 9258577
TI  - Readying a US measure of health status, the SF-36, for use in Canada.
AB  - OBJECTIVE: To culturally adapt and translate for use in French- and English
      speaking areas of Canada the Medical Outcomes Study 36-Item Short-Form Health
      Survey (SF-36), a carefully developed and standardized measure that is useful for
      assessing the outcomes for care. DESIGN: For the Canadian French version, the
      methods involved forward and backward translations, quality ratings of the
      translated product, a scaling exercise and pilot tests. A process of cultural
      adaptation, along with the scaling exercise and pilot tests, was used to create a
      form in Canadian English. RESULTS: The authors produced acceptable versions of
      the SF-36 in Canadian French and English. CONCLUSIONS: Although further
      psychometric testing of the Canadian versions of the SF-36 is desirable, they are
      now available for use in clinical practice and research in Canada.

PMID- 9258578
TI  - Obesity research continues to spring leaks.
AB  - Recent discoveries about the roles of 2 uncoupling proteins are changing the way
      we view obesity and its treatment. The author is also a coauthor of a recent
      Nature report that mice deficient in uncoupling protein 1 (UCP1) did not become
      fat, as anticipated, but lean. She found that the other uncoupling protein (UCP2)
      was up-regulated in the brown adipose tissue (BAT) of these mice, compensating,
      at least in part, for the lack of UCP1 and preventing obesity. Researchers have
      known for 40 years that the function of BAT is heat production. In 1978,
      researchers discovered UCP1, the protein responsible for this function.
      Subsequent investigation focused on the role of this protein in staving off
      obesity in animal models. In the early 1990s, surprising evidence from tissues
      other than BAT show that 20% to 40% of resting cellular energy expenditure is
      used to counter a proton leak down the electrochemical gradient across the
      mitochondrial inner membrane. This leak was found to be related to metabolic
      rate; the search for the mechanism of the leak led to the discovery of UCP2. Both
      uncoupling proteins have been found to act as leaks in mitochondrial inner
      membranes, allowing the dissipation of proton motive force. These findings could
      lead to new treatments for obesity and non-insulin-dependent diabetes mellitus.

PMID- 9258579
TI  - The learning environment and the clinician scientist.

PMID- 9258580
TI  - Training models: introduction.

PMID- 9258581
TI  - The United States Medical Scientist Training Program.

PMID- 9258582
TI  - MD/PhD programs--the Canadian experience.

PMID- 9258583
TI  - The Surgical Scientist Program at the University of Toronto: a model for training
      clinician investigators.

PMID- 9258584
TI  - Clinical/research residency programs for the clinician scientist.

PMID- 9258585
TI  - Royal College of Physicians and Surgeons of Canada Clinician Investigator
      Program.

PMID- 9258586
TI  - Report from the University of Toronto Department of Medicine Ad Hoc Committee on
      career development of clinician scientists.

PMID- 9258587
TI  - Women in biomedical research--addressing the challenges.

PMID- 9258588
TI  - Experience with nurturing clinical investigation in Alberta.

PMID- 9258589
TI  - A 10-year (1986-1995) review of data on scholar awardees in the Faculty of
      Medicine, University of Toronto.

PMID- 9258590
TI  - Survival of clinician scientists.

PMID- 9258591
TI  - Federal funding and university science: lessons learned from lobbying government.

PMID- 9258592
TI  - Transformation of a set of slices rotated on a common axis to a set of Z-slices:
      application to three-dimensional visualization of the in vivo human lens.
AB  - A technique that transforms a set of images acquired as a rotating frame about an
      axis (Z axis) into a set of images along the Z axis in presented. This technique
      is applied to the three-dimensional visualization of the in vivo human lens. A
      Scheimpfling slit camera acquired 60 optical images through the in vivo human
      lens. Between each image acquisition the plane containing the slit beam of light
      was sequentially rotated. This set of 60 images was transformed into a new stack
      of images on the Z axis. The transformed stack of Z images was visualized with
      volume rendering software.

PMID- 9258593
TI  - The use of deblurring technique for improving the longitudinal resolution in
      helical CT of the head and neck region.
AB  - We evaluated the use of deblurring technique by digital deconvolution for
      improving the longitudinal resolution in helical CT in a phantom and CT images of
      head and neck patients. After performing the helical scanning, overlapped axial
      images were reconstructed at 1/10 of the actual collimation. Then, the deblurring
      technique was performed. Results revealed that the resolution of slice profiles
      was improved after deblurring. Further, the longitudinal resolution increased as
      the strength of the deconvolution increased, at the expense of an increase in
      helical artifacts. The sharpness and visualization of horizontally running
      structures were improved in the reconstructed MPR, MPVR, MIP and 3D images in
      both the phantom and the images of all patients. Also, visualization of the
      peripheral vessels in CTAs was improved.

PMID- 9258594
TI  - Performance of asynchronous transfer mode (ATM) local area and wide area networks
      for medical imaging transmission in clinical environment.
AB  - Asynchronous transfer mode (ATM) technology emerges as a leading candidate for
      medical image transmission in both local area network (LAN) and wide area network
      (WAN) applications. This paper describes the performance of an ATM LAN and WAN
      network at the University of California, San Francisco. The measurements were
      obtained using an intensive care unit (ICU) server connecting to four image
      workstations (WS) at four different locations of a hospital-integrated picture
      archiving and communication system (HI-PACS) in a daily regular clinical
      environment. Four types of performance were evaluated: magnetic disk-to-disk,
      disk-to-redundant array of inexpensive disks (RAID), RAID-to-memory, and memory
      to-memory. Results demonstrate that the transmission rate between two
      workstations can reach 5-6 Mbytes/s from RAID-to-memory, and 8-10 Mbytes/s from
      memory-to-memory. When the server has to send images to all four workstations
      simultaneously, the transmission rate to each WS is about 4 Mbytes/s. Both
      situations are adequate for radiologic image communications for picture archiving
      and communication systems (PACS) and teleradiology applications.

PMID- 9258595
TI  - Evaluation of a neural network classifier for pancreatic masses based on CT
      findings.
AB  - We have investigated a neural network classifier based on CT findings extracted
      by a radiologist for the differential diagnosis between the pancreatic ductal
      adenocarcinoma and mass-forming pancreatitis, and compared its classification
      performance with that of Bayesian analysis, Hayashi's quantification method II,
      and radiologists. The three computerized classification methods were designed to
      classify categorized CT findings extracted by a radiologist, and were trained and
      tested on 71 cases. There was comparable performance between the neural the
      network, the Bayesian analysis, Hayashi's quantification method II, and the
      radiologists, in classifying pancreatic carcinoma and inflammatory mass.

PMID- 9258596
TI  - Quantitative assessment of abdominal aortic atherosclerosis observed in CT scans.
AB  - Calcification of the aorta is characteristic of atherosclerotic disease. A novel
      numerical index for quantitating the extent of calcification observed in computed
      tomography (CT) scans has been developed. The index weights the fractional area
      of the aorta showing calcifications with the average calcium density in the
      plaques. It obviates the need for manual tracing of the calcifications, and
      avoids the arbitrary nature and lack of reproducibility of the "calcium score"
      system currently used in assessing CT scans. Continuously different levels of
      calcification were distinguished in the abdominal aortas of a group of Kuwaiti
      females (n = 20), with a linear correlation coefficient between index value and
      age of 0.914 (P < 0.0001) over three decades. The index is generally applicable
      to all arterial calcifications, and could be used to monitor the effect of
      therapeutic regimes. It could easily be modified for use with 3D reconstructions
      obtained from CT helical scanning or MRI.

PMID- 9258597
TI  - MR imaging of Wilson's disease: contrast enhancement of the cerebral cortex, and
      corticomedullary junction.
AB  - A patient with Wilson's disease is reported whose brain MR imaging study
      disclosed enhancement of the cerebral cortex, and corticomedullary junction after
      administration of contrast medium, in the absence of a clinically detectable
      ischemic condition. It is difficult to explain such contrast enhancement.
      However, we would suggest that a "vasculitis" secondary to accumulation of copper
      in the walls of the small vessels may be the causative factor. Further studies
      are required to investigate the clinical and radiological significance of
      contrast enhancement of the cerebral cortex and corticomedullary junction on MR
      images in patients with Wilson's disease.

PMID- 9258598
TI  - MR demonstration of cerebral hemimegalencephaly associated with cerebellar
      involvement (total hemimegalencephaly).
AB  - Hemimegalencephaly or unilateral megalencephaly is a rare malformation
      characterized by overdevelopment of all or part of one cerebral hemisphere.
      Although previous pathological studies noted an associated overdevelopment of the
      ipsilateral cerebellar hemisphere in a few cases, to the best of the author's
      knowledge, such an association has not yet been reported in the radiological
      literature. This paper reports a 1-yr-old patient with hemimegalencephaly of the
      right cerebral hemisphere, and hemimegalencephaly of the ipsilateral cerebellar
      hemisphere. The ipsilateral half of the brainstern was also enlarged. This
      condition is suggested to be labelled as "total hemimegalencephaly".

PMID- 9258599
TI  - A tonsillolith seen on MRI.
AB  - A case of a large tonsillolith visualized by magnetic resonance imaging is
      presented. Although otolaryngologists are well aware of this entity, few
      radiologists are. The importance of distinguishing tonsilloliths from other
      structures by MRI is discussed.

PMID- 9258600
TI  - Molecular cytogenetics of prostate cancer.
AB  - Prostate cancer is the most common malignancy among men in many developed
      countries. One-fourth of prostate cancers are diagnosed at metastatic stage but
      there is no curative treatment for such disease and palliative androgen
      withdrawal therapy remains the most used one. Thus, understanding the molecular
      events that underlie the development and progression of prostate cancer could
      help to answer many clinical questions on its treatment. In this review article,
      I want to illustrate some of the most interesting findings (by fluorescence in
      situ hybridization and comparative genomic hybridization) in the molecular
      cytogenetics of prostate cancer.

PMID- 9258601
TI  - Antisense regulation of oncogenes in human cancer.
AB  - Gene transfer or manipulation of genes for the treatment of cancer is a rapidly
      expanding field. In recent years, much attention has been focused on manipulating
      cancer genes and applying antisense technology in therapeutic ways. Consequently,
      antisense RNA control is now recognized as a specific means of regulating gene
      expression at the posttranscriptional level. Defects in vital genes occur in many
      human diseases, including cancer, defects that may be due to an accumulation of
      mutations in the genes that leads to the production of faulty proteins. Although
      the biological significance of such mutant proteins still remains in question,
      recent experiments have demonstrated that genes overproducing faulty proteins are
      often associated with increased tumor cell growth. Moreover, using a stretch of
      antisense RNA to block the production of such defective proteins can effectively
      silence their genes; as a result, tumor cells stop dividing rapidly and revert to
      a more normal phenotype. Therefore, antisense RNA technology could have a
      significant impact on cancer gene therapy. Here, we have tried to give
      comprehensive coverage to some major cases of antisense RNA control of cancer
      related genes highlighting the biological systems involved, the efficacy of the
      antisense RNA in altering target gene function, and how such antisense control
      affects the malignant phenotype. Furthermore, the therapeutic potential of the
      antisense technique depends on the in-depth understanding of the target gene
      function and its role in carcinogenesis.

PMID- 9258602
TI  - Implication of cyclin D1 in malignant lymphoma.
AB  - The chromosomal translocation t(11;14)(q13;q32) is observed in a number of
      lymphoid malignancies but is specifically associated with a particular subtype of
      non-Hodgkin's lymphoma called mantle cell lymphoma, where it is observed in up to
      70% of cases. This translocation juxtaposes IGH sequences at 14q32 to a region
      variously termed BCL1/PRAD1 at 11q13, on the derivative chromosome 11. Detailed
      molecular analysis identified BCL1 to be a gene coding for the G1 cyclin, cyclin
      D1, which is an important regulator of the G1/S transition of the cell cycle.
      Cyclin D1 overexpression is observed in a vast majority of mantle cell lymphoma
      and lymphoid malignancies with 11q13 rearrangement, thereby confirming BCL1, now
      referred to as CCND1, as the gene targeted by these rearrangements. In this
      review, following a brief discussion of the role of cyclin D1 in cell cycle
      regulation, we discuss the mechanisms and pathogenetic impact of cyclin D1
      activation in lymphoproliferative disorders with 11q13 rearrangement. We also
      review a number of the diagnostic strategies available for detection of CCND1
      rearrangement/overexpression, with particular emphasis on applications for mantle
      cell lymphoma.

PMID- 9258603
TI  - The role of metalloproteinases and their inhibitors in hematological disorders.
AB  - The balance between the activities of matrix metalloproteinases (MMPs) and the
      tissue inhibitors of metalloproteinases (TIMPs) is an important control point
      during the turnover of the extracellular matrix. Previous studies have
      demonstrated that an uncontrolled rate of production of these proteins leads to
      various pathological conditions. Overexpression of MMPs by malignant cells can
      increase the invasive behavior of solid tumors and their metastatic potential. In
      an increasing number of reports, it has become evident that expression of MMPs
      and TIMPs is not restricted to solid tumors. Normal and malignant hematological
      cells also express these proteins and play a pivotal role in the hematological
      cell physiology. In addition to modifying the extracellular matrix, MMPs and
      TIMPs exert other functions in hematological cells, including growth-factor
      activity, removal of cell-surface receptors, and autoimmunity. The goal of this
      review is to gather recent studies concerning the properties of MMPs and TIMPs in
      hematological cells, their regulation of gene expression, their cellular
      distribution, and their potential role in the pathogenesis of hematological
      disorders such as inflammation and neoplasia.

PMID- 9258604
TI  - Resistance mechanisms and their regulation in lung cancer.
AB  - Data obtained from multiple sources indicate that no single mechanism can explain
      the drug resistance and the poor prognosis of patients with lung cancer. The
      resistance-related proteins P-glycoprotein, glutathione-dependent enzymes,
      topoisomerase II, metallothioneins, O-6-alkylguanine-DNA alkyltransferase,
      thymidylate synthase, dihydrofolate reductase and heat shock proteins have been
      found in lung carcinomas, but these alone cannot explain the drug-resistant
      phenotype. Cell cycle-related proteins, angiogenic factors, protooncogenes, and
      tumor suppressor genes also play a role in the phenotype that is resistant lung
      cancer. A key future challenge involves determining the relative quantitative
      contributions of each of these mechanisms to overall resistance.

PMID- 9258605
TI  - Myb-induced transformation.
AB  - The c-myb protooncogene has been implicated in the development of avian and
      murine hematopoietic neoplasms of the myeloid and lymphoid lineages. The
      transcription factor encoded by this gene has a dual function in oncogenesis
      because it regulates genes that prevent apoptosis and genes involved in cellular
      proliferation. c-myb has repeatedly been a target of retroviral insertional
      mutagenesis. The most common mechanism by which retroviruses activate c-myb's
      oncogenic potential is by providing transcriptional control that results in
      constitutive expression, a feature that is consistent with the demonstration that
      ectopic expression of c-myb can prevent growth arrest of differentiating
      hematopoietic cells. In a less common mechanism of activation, carboxyl(C)
      terminal truncation renders the c-Myb protein more stable and active in
      transcriptional transactivation. Interestingly, the ability of v-Myb, a product
      of the avian myeloblastosis virus (AMV), to cause rapid transformation of cells
      in vivo and in vitro can be explained by the combined effects of deregulated
      expression through the retroviral LTR, N- and C-terminal truncation, and
      activating mutations in its DNA binding domain. Although c-myb's involvement in
      human leukemia has been suggested, it has never been clearly established and
      should be investigated further.

PMID- 9258606
TI  - Oncogene-initiated aberrant signaling engenders the metastatic phenotype:
      synergistic transcription factor interactions are targets for cancer therapy.
AB  - Certain p21GTPases (notably Ras) and some of their guanine nucleotide exchange
      factors (e.g., Ost, Dbl, Tiam) and downstream mediators (e.g., Raf, Myc) have the
      potential to promote the development of malignancies because they can enhance the
      transcription of genes that foster the tumorigenic and metastatic phenotype.
      Among these are genes that stimulate cell proliferation, confer immortality, and
      facilitate the invasion of normal tissues. Oncogenes upstream of Ras-cell surface
      receptors such as ErbB2/Neu, Met, or Trk (and their ligands), and nonreceptor
      cytoplasmic protein tyrosine kinases such as Src and Abl-not only can act through
      Ras but also contribute additional signals. This review presents a synopsis of
      our understanding of signaling pathways controlled by the p21GTPases, with a
      focus on transcription factors regulated by the pathways. Mutations in one or
      more of the elements in these signaling pathways are invariably found in cancer
      cells. Crosstalk among the pathways may explain how some forms of stress can
      contribute to the development of a malignancy. Abnormal signaling leads to
      modified cytoskeletal structures and permanently altered (i.e., self-sustaining
      or epigenetic) transcription of target genes. A common therne is that genes whose
      transcription is elevated to the greatest extent by Ras often have in their
      promoters juxtaposed binding sites for two different transcription factors
      (particularly those in the Fos/Jun, CREB/ATF, NFkB, and Ets families) each of
      which is activated and such that together they synergize to augment transcription
      substantially. Some of these transcription factors can also act as oncogenes in
      certain cell types when appropriately modified and expressed. This unifying theme
      among many different cancers suggests that strategies to restore the balance
      among the signaling pathways or to suppress synergistic interactions between
      transcription factors may prove broadly useful in reversing the malignant
      phenotype.

PMID- 9258607
TI  - Characterization of hemolytic and cytotoxic Gallysins: a relationship with
      arylphorins.
AB  - Gallysin-1, an inducible effector protein in the protective response of Galleria
      mellonella larvae is a 75 kDa component of hemolytically active material (HAM)
      isolated from immune cell-free hemolymph. The sequence of the first 20 N-terminal
      amino acids of the antibacterial protein Gallysin-1 is identical to the predicted
      sequence of the first 20 amino acids of the Galleria arylphorin Lhp76 (larval
      hemolymph protein 76). A murine monoclonal antibody to the 20 amino acid N
      terminal peptide of Gallysin-1 (GYPQYHYDVETRKLDPSLVN) provides additional
      evidence for a link between Gallysin-1 and Lhp76, and is used to characterize HAM
      further. HAM, initially characterized as a mixture of two proteins, Gallysin-1
      and a 69 kDa component is now identified as a 450-500 kDa heteromultimer,
      designated Gallysin. In vivo levels of Gallysin rise during the effector phase of
      an induced immune response. The monoclonal antibody inhibits the hemolytic
      activity of Gallysin. In addition to a hemolytic activity for mammalian
      erythrocytes, Gallysin possesses a cytotoxic activity for the human tumor cell
      line, K562. Lipopolysaccharides (LPS) and a Pseudomonas aeruginosa vaccine induce
      a cytotoxic activity which reaches its maximum levels in the hemolymph early (2
      hours post-vaccination) in the protective response. The partially purified
      cytotoxic material (Cyt-M) obtained from cell-free hemolymph collected 2 hours
      after vaccination has hemolytic activity and shows structural similarities to
      Gallysin and Lhp76. The previously established role of Gallysin-1 as an effector
      protein in the protective response of Galleria mellonella indicates that
      arylphorins may play a role in insect immune responses.

PMID- 9258608
TI  - Peroxidase-release associated with phagocytosis in Mytilus galloprovincialis
      haemocytes.
AB  - Fluorescence spectra of the supernatant of adherent haemocyte monolayers from
      Mytilus galloprovincialis, supplemented with homovanillic acid or with a tyrosyl
      peptide glycylglycyltyrosine (GGY), were recorded before and after stimulation by
      zymosan. The formation of fluorescent derivatives was observed to have spectral
      characteristics similar to those of fluorescent compounds generated by the
      exposure of homovanillic acid or GGY to a horseradish peroxidase/hydrogen
      peroxide system in vitro. Lucigenine-enhanced chemiluminescence (CLluc) of M.
      galloprovincialis haemocytes stimulated by zymosan or by phorbol ester (PMA) was
      measured in the presence and absence of sodium azide, a peroxidase inhibitor.
      Sodium azide inhibited the CLluc of haemocytes stimulated by zymosan, an
      effective stimulus for myeloperoxidase secretion in human polymorphonuclear
      leukocytes, but not the CLluc of haemocytes stimulated by PMA, indicating the
      presence of peroxidases with some properties of myeloperoxidase, in adherent
      haemocytes from M. galloprovincialis.

PMID- 9258609
TI  - Localization of a putative inositol 1,4,5-triphosphate receptor in the Limulus
      granulocyte.
AB  - The horseshoe crab (Limulus polyphemus) granulocyte (GR) degranulates upon
      contact with bacteria and release factors that mediate an immune response.
      Stimulated cells produce IP3, which binds to receptors (IP3R, M.W.240-300 kD)
      that function to release stored Ca2+ into the cytoplasm that mediates
      degranulation. This mechanism is believed to mediate exocytosis in the Limulus GR
      but IP3R in the GR has not been shown. The present study utilized monoclonal
      antibody 4C11 and a commercially available anti-IP3R antibody, both of which
      label amino acids of the N-terminal of all known isoforms. Electron microscopy,
      immunohistochemistry, SDS-PAGE, and Western blot analysis, which employed the use
      of the two antibodies, demonstrates that a putative IP3R exists in the: plasma
      membrane, smooth surfaced vesicles, nucleus and nuclear membrane. We hypothesize
      that this putative IP3R is involved in mediating the immune response of the
      Limulus GR.

PMID- 9258610
TI  - Damselfish with neurofibromatosis exhibit cytotoxicity towards retrovirus
      infected cells.
AB  - Lymphocytes from tumor-bearing damselfish are cytotoxic towards target cell lines
      derived from damselfish neurofibromatosis. These cell lines contain at least one
      retrovirus which appears to be related to the etiology of the disease. The
      current studies were designed to characterize the effectors of this cytotoxic
      reaction. Data presented here show that cells separated using an antibody
      (5C6.10.4) directed towards non-specific cytotoxic cells of catfish sequesters
      all antitumor activity in the 5C6.10.4 negative population. Thus, damselfish
      5C6.10.4 positive cells bind to tumor targets, but do not contribute to target
      cell death. In contrast, 5C6.10.4 positive cells are cytotoxic towards xenogeneic
      erythrocytes. Cytotoxicity of splenocytes from animals inoculated with virus
      purified from the 88-503 cell line suggested that prior exposure to the
      retrovirus enhanced reactivity, especially towards 88-503. In addition,
      cytotoxicity was significantly greater in tumor homogenate injected animals that
      resisted tumor development for more than 5 months as compared to those that
      developed tumors quickly. Lastly, cytotoxic responsiveness towards primary
      cultures of mock and virus infected autologous and allogeneic cells implies that
      the cytotoxic effector is directed towards retrovirus infected cells.

PMID- 9258611
TI  - Optimization of an in vitro assay which measures the proliferation of duck T
      lymphocytes from peripheral blood in response to stimulation with PHA and ConA.
AB  - The in vitro proliferative responses of duck PBMCs purified from Ficoll-Paque
      density gradients to the mitogens PHA and ConA show a great deal of duck-to-duck
      variation. Better responses were consistently obtained by using nylon wool
      fractionation to increase the proportion of duck T lymphocytes in PBMC
      preparations and then culturing these preparations with homologous monocytes,
      purified from PBMC preparations by their adherence properties. We have also
      established that the addition of homologous red blood cells enhances the in vitro
      proliferative responses of duck T lymphocytes, especially when limiting doses of
      PHA and ConA are used. Duck T lymphocytes showed greater and more consistent
      proliferation when cultures were incubated at 37 degrees C as compared to
      incubation at 41.6 degrees C. The improved consistency of higher proliferative
      responses with this assay should make it more suitable for detecting in vitro
      proliferative responses of antigen-specific T lymphocytes, as a measure of in
      vivo induced cell mediated immune responses.

PMID- 9258613
TI  - Automated cytologic screening devices and malpractice liability.

PMID- 9258612
TI  - Characterization of five monoclonal antibodies specific for swine class II major
      histocompatibility antigens and crossreactivity studies with leukocytes of
      domestic animals.
AB  - A set of five monoclonal antibodies (mAb) against porcine major
      histocompatibility complex (MHC), or swine leukocyte antigens (SLA), class II
      molecules has been characterized. These mAbs appear to recognize monomorphic
      determinants on SLA-DR (2F4, 1F12 and 2E9/13) and SLA-DQ (BL2H5 and BL4H2)
      molecules, as assessed by flow cytometry and immunoprecipitation. By Western
      blot, the 2F4, 1F12, BL2H5 and BL4H2 epitopes were located on the beta-chains of
      these molecules. mAbs 2F4 and 1F12 crossreact with leucocytes of dog, cattle,
      horse and human; mAbs 2E9/13, BL2H5 and BL4H2 bind leucocytes of cattle but not
      those of human, dog and horse. These mAbs effectively blocked the mixed
      lymphocyte reaction and the proliferative response to viral antigens (African
      swine fever virus) and to staphylococcal enterotoxin B. Therefore, these mAbs can
      be useful reagents for studying MHC class II molecules of pig and crossreactive
      species, and the immunological processes where they are involved.

PMID- 9258614
TI  - Brush technique in ocular surface cytology.
AB  - New techniques are being searched for the evaluation of cellular morphology and
      population of ocular surface. Impression cytology is one of the most preferred
      techniques in ocular surface sampling in dry eye, keratitis, and conjunctivitis.
      We evaluated and compared the efficacy of impression and brush cytology in 63
      patients. All of the samples collected by the brush technique were sufficient for
      diagnosis: 88% of the slides revealed abundant cells and 12% adequate number of
      cells. In 21% of the samples observed by impression cytology the cell number was
      inadequate for diagnosis. In 58% of them the cells were abundant and in 21% few
      cells were observed. This study proved the value of brush cytology in collecting
      ocular surface cells.

PMID- 9258615
TI  - Fine-needle sampling of salivary gland lesions. IV. Review of 50 cases of
      mucoepidermoid carcinoma with histologic correlation.
AB  - Fine-needle sampling (FNS) of 50 mucoepidermoid carcinomas, including 44 primary
      tumors, five local recurrences, and one lymph node metastasis, was performed
      preoperatively in 44 patients. Concordant cytologic diagnoses were established in
      only 19 (38%) tumors, whereas 15 (30%) were classified as carcinoma, five (10%)
      as suspicious, and six (12%) as benign tumors. The material was insufficient for
      cytologic evaluatin in five (10%) cases. The tumors were classified
      histologically as high-, intermediate-, and low-grade in 15, 13, and 22 cases,
      respectively. The quality of diagnosis did not vary between high- and
      intermediate-grade, but was lower in low-grade tumors: Malignancy was diagnosed
      or suspected in 13 (87%) high-grade tumors, 11 (85%) intermediate-grade tumors,
      and 15 (68%) low-grade tumors. In conclusion, FNS is an accurate technique in
      high- or intermediate-grade mucoepidermoid carcinomas, but quite unsatisfactory
      in low-grade tumors.

PMID- 9258616
TI  - Pregnancy-related changes: a retrospective review of 278 cervical smears.
AB  - Pregnancy-related physiologic changes are well recognized. However, the normal
      range of changes as reflected in the cervical smear have not been adequately
      described. Review of 278 abnormal cervical smears from 153 pregnant/preabortal
      and 125 postpartum/ abortal patients revealed the following: 21 high-grade
      squamous intraepithelial lesion (HGSIL) cases, 46 low-grade squamous
      intraepithelial lesion (LGSIL) cases, 185 atypical squamous cells of undetermined
      significance (ASCUS) cases, and 26 atypical glandular cells of undetermined
      significance (AGUS) cases. Surgical correlation (excluding 18 products of
      conception and 153 placentas) was available in 98 (35%) of the cases. Dysplasia
      was confirmed on biopsy of 11 cases cytologically diagnosed as HGSIL (7 CINII/III
      and 4 CIN I), 19 cases cytologically diagnosed as LGSIL (6 CIN II/III and 13 CIN
      I), 35 cases of ASCUS (4 CIN II/III and 31 CIN I), and 2 cases of AGUS (1 CIN III
      and 1 CIN I). Decidualization was present in six cervical and three endometrial
      biopsies. The remaining 180 cases revealed pregnancy-related changes in most of
      the atypical groups and a few in the dysplasia groups. With pregnancy, both
      cervical glands and stroma undergo physiologic changes. These result in squamous
      metaplasia due to ectropion and cells with hypervacuolated cytoplasm and atypical
      nuclei reflecting endocervical gland hyperplasia and/or Arias-Stella reaction.
      The decidual cells are large, with variably staining cytoplasm and a large
      nucleus. Degenerated decidual or trophoblastic cells can also shed from the
      endometrium and mimic HGSIL. Despite the caution required in this population,
      dysplastic changes should not be underestimated.

PMID- 9258617
TI  - Utility of fine-needle aspiration in the diagnosis of granulomatous lesions of
      the breast.
AB  - Fourteen cases of granulomatous mastitis (GM) studied by fine-needle aspiration
      (FNA) are reviewed and nine cytologic features (necrosis, neutrophil
      granulocytes, foamy cells, plasma cells, granulomas, epitheloid cells,
      multinucleated giant cells of foreign body type and Langhans' type, duct cells,
      and the presence of acid-fast bacilli) are reappraised in a semiquantitative
      manner. The main objective of this study was to find out if one or more of these
      features would permit the various granulomatous entities identified in surgical
      pathology to be separated cytologically. The results suggest that FNA does not
      permit the various granulomatous lesions identified in surgical pathology to be
      differentiated, since in this series different entities share a common cytologic
      pattern. Only the presence of acid fast bacilli in smears would enable a
      tuberculous etiology to be diagnosed. The opinion is put forward that the term GM
      should be avoided in the cytologic report and substituted by the noncommitted
      term "granulomatous lesion of the breast.

PMID- 9258618
TI  - Complementary value of five carcinoma markers for the diagnosis of malignant
      mesothelioma, adenocarcinoma metastasis, and reactive mesothelium in serous
      effusions.
AB  - Cytological slides of serous fluids of 41 malignant mesotheliomas, 88 metastatic
      adenocarcinomas, and 25 reactive effusions were immunostained with the antibodies
      anti-CEA, MOC-31, Leu-M1, Ber-EP4, and B72.3. Most mesotheliomas and all reactive
      fluids failed to stain with these antibodies. The sensitivity of the five markers
      to detect carcinoma cells differed remarkably. Especially MOC-31, Ber-EP4, and
      B72.3 stained with a high number of carcinoma cases and the complemetary value of
      Ber-EP4 and B72.3 to immunostain carcinoma cells was impressive: 94% of the
      metastatic adenocarcinoma cases reacted with Ber-EP4 or B72.3 in contrast to 1 of
      41 malignant mesotheliomas.

PMID- 9258619
TI  - Diagnostic pitfalls in fine-needle aspiration biopsy of the mediastinum.
AB  - A retrospective review of 189 fine-needle aspiration (FNA) biopsies of the
      mediastinum from four university medical centers was performed. Review of Diff
      Quick- and Papanicolaou-stained direct smears was performed from a series of 189
      FNA biopsies along with surgical pathology correlation obtained in 42% of the
      cases. There were 28 (14.8%) nondiagnostic or unsatisfactory for diagnosis cases.
      Of the satisfactory FNA specimens with histologic correlation, 12 cases (6%) were
      discordant. These errors primarily involve subclassification of small-cell
      malignancies involving the mediastinum, including a misdiagnosis of small-cell
      carcinoma for lymphoma. Large-cell lesions that were problematic included the
      accurate diagnosis of Hodgkin's lymphoma including the separation from non
      Hodgkin's lymphoma. Large-cell lymphoma with sclerosis was misinterpreted in two
      cases due to distortion of cells by the mesenchymal tissue and sparsely cellular
      smears. In two cases classification of primary germ-cell tumors and separation
      from metastatic carcinoma was a problem. In general, FNA of the mediastinum is an
      accurate procedure, but can be challenging in a minority of cases due to sparse
      cellularity of the lesions and accurate classification of a variety of neoplasms
      that occur in this region. These 12 discordant cases serve as the basis of our
      report.

PMID- 9258620
TI  - Immunostaining of estrogen receptor, progesterone receptor, MIB1 antigen, and c
      erbB-2 oncoprotein in cytologic specimens: a simplified method with formalin
      fixation.
AB  - An effective but simple fixation protocol for the immunocytochemical staining of
      cytologic smears for estrogen and progesterone receptors, the Ki-67 antigen
      (using MIB1 antibody), and c-erbB-2 protein is described. One hundred twenty
      seven smears from a variety of malignant and benign breast lesions showed good
      preservation of antigenicity when subjected to the following fixation protocol:
      Freshly made smears were air-dried for 20 min to 14 h at 22 degrees C before
      immersing in 10% buffered formalin for 2-14 h. Immunostaining followed microwave
      stimulated epitope retrieval. There was strong concordance of staining with
      corresponding tissue sections in 15 cases of malignant tumors (ER: r = 0.7381;
      PR: r = 0.6684; MIB1: r = 0.7234). Immunostaining staining, when delayed for 5-10
      days in about half the smears, showed no noticeable difference in reactivity,
      attesting to effective storage of the formalin-fixed smears at room temperature.

PMID- 9258621
TI  - Cytologic diagnosis of Ki-1 lymphoma in pleural and peritoneal effusions: a case
      report.
AB  - This is a report of a case of Ki-1-positive large-cell anaplastic lymphoma in an
      87-year-old man diagnosed on pleural and peritoneal fluids by cytomorphologic and
      immunohistochemical examination. Papanicolaou-stained smears revealed many
      single, large neoplastic cells containing one or two nuclei with occasional
      multinucleated cells having a wreath-like nuclear arrangement. The tumor cells
      expressed Ki-1 antigen and epithelial membrane antigen. This is the first known
      report of Ki-1 lymphoma diagnosed initially on cytologic examination of pleural
      and peritoneal fluids.

PMID- 9258622
TI  - Cytopathology of follicular dendritic cell tumors.
AB  - Follicular dendritic cell tumors are rarely described entities, arising from
      antigen-presenting immune accessory cells, found within B-lymphocyte follicles in
      nodal and extranodal sites. We report two cases, one associated with Castleman's
      disease, in whom fine-needle aspiration biopsy was performed followed by surgical
      biopsy. The diagnosis was confirmed using immunoreactivity with CD21 and CD35
      antibodies and by ultrastructural demonstration of interdigitating cell processes
      with desmosomes. Both the cytologic and histologic findings are presented, and
      the differential diagnoses are discussed. Awareness of this entity and
      recognition of the pathologic features may lead to a presumptive diagnosis which
      must be confirmed using imunohistochemistry and/or electron microscopy.

PMID- 9258623
TI  - Fine-needle aspiration diagnosis of carotid body tumor: report of a case and
      review of experience with cytologic features in four cases.
AB  - A 45-yr-old female presented with a left upper cervical swelling of 4 yr
      duration. The clinical suspicion of carotid body tumor (CBT) was confirmed by
      imaging findings, fine-needle aspiration (FNA) cytology, and histology of the
      resected tumor. Review of our experience with four cases including the present
      one during 10 yr (1984-1994) showed that the age of the patients ranged from 35
      to 45 yr with a mean of 40.8 yr. All four cases were females and had left-sided
      upper cervical swelling. Clinically one case was diagnosed as cervical
      lymphadenopathy and there was clinical suspicion of CBT in two cases. Findings of
      digital subtraction angiogram in four cases and ultrasonography including Doppler
      ultrasound vascular imaging in three cases were consistent with CBT. The
      cytodiagnosis was CBT in three cases and inadequate (blood only) in one case. The
      analysis of detailed cytologic features in three cases revealed blood-rich
      aspirate with poor to moderate cellularity, indistinct cell outline, and acinar
      formation. Giant bare nuclei, spindle-shaped tumor cells, and cytoplasmic
      granulations were observed in two cases each. Histopathology of the resected
      tumors in two cases confirmed the cytodiagnosis of CBT. FNA cytology played a
      useful role in arriving at a tissue diagnosis of this rare neoplasm.

PMID- 9258624
TI  - Massive crystal-storing histiocytosis associated with low-grade malignant B-cell
      lymphoma of MALT-type of the parotid gland.
AB  - Massive crystal deposition is unusual in lymphoproliferative disorders. In this
      report, a mucosa-associated lymphoid tissue (MALT) low-grade B-cell lymphoma of
      the parotid gland containing large numbers of crystal-storing histiocytes is
      described. The patient, an 81-yr-old female, presented with a history of long
      standing left parotid gland enlargement. FNA cytology of the tumor showed a
      lymphoplasmacytic infiltrate and sheets of large benign histiocytes with abundant
      eosinophilic intracytoplasmic inclusions. Paraffinsection immunohistochemistry
      performed on the cell block demonstrated that the histiocytic cells were
      immunoreactive for the KP-1 (CD-68) antibody and monotypic for cytoplasmic IGM
      and L-light chain. The cytological diagnosis was consistent with a low-grade B
      cell lymphoma with plasmacytic differentiation associated with crystal-storing
      histiosis. A periparotid lymph node was biopsied and showed involvement by a
      monocytoid B-cell lymphoma with plasmacytic differentiation and crystal-storing
      histiocytosis in the pericapsular region.

PMID- 9258625
TI  - Direct intrauterine sampling: the IUMC Endometrial Sampler.
AB  - Endometrial cytology has been studied for more than 25 years, and a variety of
      cytologic devices have been developed for direct sampling of the endometrium. The
      quality of endometrial samples procured by various devices is markedly different
      and greatly affects the diagnostic accuracy. A new endometrial sampling device,
      the IUMC Endometrial Sampler, was developed at the Indiana University Medical
      Center and approved by the Food and Drug Administration for general medical use.
      This device is intended for the early detection of endometrial carcinoma and its
      precursors. It can be used to monitor the endometrial condition of patients
      receiving estrogen replacement therapy or tamoxifen. It is also useful for the
      procurement of uncontaminated endometrial samples for microbiologic studies from
      patients with suspected endometritis. It has the potential to be used for
      endometrial dating for patients with infertility disorders. In our clinical
      trials and sampling tests using hysterectomy specimens, adequate and
      representative endometrial samples without contamination from endocervix and
      vagina were consistently obtained by this device. The procedure of endometrial
      sampling using this device and the preparation techniques for endometrial
      brushing specimens are discussed and illustrated.

PMID- 9258626
TI  - Bronchoalveolar lavage: comparison of nucleopore filters and direct smear
      preparations.
AB  - To determine whether cytopreparation affects the diagnostic yield of
      bronchoalveolar lavage specimens, we compared 50 lavage samples by using two
      methods. One nucleopore filter preparation and four direct slides were prepared
      on each sample submitted. All slides were stained by the Papanicolaou method.
      Assessment of cellularity, cellular preservation, and an independent diagnosis
      were rendered on each sample for both preparatory methods. Statistical analysis
      showed no difference in cellularity between the two methods (P = .06). The degree
      of nuclear and cytoplasmic preservation was higher using the direct method,
      although this did not appear to affect diagnosis in this study. One major
      discrepancy in diagnosis was observed between the two methods. By prospectively
      comparing nucleopore filter and direct preparation of bronchoalveolar lavages, we
      found that there was minimal affect on either cellularity or diagnosis. We
      conclude that either method delivers reliable cytologic results.

PMID- 9258627
TI  - Mitochondrial injury. Lessons from the fialuridine trial.
AB  - Fialuridine is an antiviral agent with potent activity against hepatitis B virus
      replication in vitro and in vivo. In a phase II study, 7 of 15 patients
      experienced severe toxicity due to the drug after 9 to 13 weeks of treatment.
      Adverse effects included nausea, vomiting and painful paraesthesia; subsequently,
      hepatic failure, pancreatitis, neuropathy, myopathy and lactic acidosis
      developed, probably due to multisystem mitochondrial toxicity. Possible
      mechanisms of fialuridine toxicity include mitochondrial injury and pyruvate
      oxidation inhibition. While other nucleoside analogues have shown evidence of
      inducing mitochondrial injury (zidovudine, didanosine, zalcitabine), others to
      date have not (lamivudine, famciclovir). Specific recommendations for future
      study of existing and new nucleoside analogues include testing for toxicity after
      prolonged incubation, specific investigations to measure mitochondrial function,
      toxicological tests and well designed clinical trials with appropriate testing to
      monitor for any adverse effects on mitochondrial integrity and function.

PMID- 9258629
TI  - Drug-induced Clostridium difficile-associated disease.
AB  - Clostridium difficile is a spore-forming anaerobe that resides in the colon and
      is capable of producing gastrointestinal disease in humans. Factors such as
      previous exposure to antibacterials and some antineoplastic agents have been
      reported to promote the overgrowth of C. difficile, with subsequent liberation of
      potent exotoxins that induce inflammation in the colonic mucosa. Colonisation
      rates vary, and are higher during infancy and hospitalisation, compared with
      healthy adults. Although many antibacterials have been reported to induce
      disease, those agents that achieve high concentrations in the intestinal lumen
      and are active against bowel flora are more likely to promote overgrowth of C.
      difficile. Agents with a high potential to induce C. difficile-associated disease
      (CDAD) include aminopenicillins, cephalosporins and clindamycin. These
      antibacterials are capable of reducing normal colonisation resistance within the
      colon. The exact incidence of CDAD is unknown. Some reports suggest an incidence
      of 1 to 3 infections per 100,000 courses of outpatient oral therapy. The spectrum
      of illness of CDAD can range from mild diarrhoeal disease to severe colitis,
      toxic megacolon and sepsis. Fatalities have occurred in some cases.
      Discontinuation of the offending antibacterial in patients with mild disease is
      often sufficient to alleviate symptoms. For those with moderate to severe
      illness, metronidazole and vancomycin are reported to be equally efficacious.
      Increasing resistance of enterococci to vancomycin limits its use to patients
      with severe life-threatening infections. Patients with recurrent disease usually
      respond well to the same course of therapy as was used to treat the initial
      infection. CDAD is potentially preventable when appropriate antibacterial
      selection and infection control measures are implemented.

PMID- 9258631
TI  - Primary stable anterior instrumentation or dorsoventral spondylodesis in
      spondylodiscitis? Results of a comparative study.
AB  - The operative results of 23 patients with a specific or unspecific
      spondylodiscitis were documented over 2 years after the focus of the inflammation
      had been eradicated, bone chip had been interposed and a CDH instrumentation had
      been performed by an anterior approach only. These outcomes were compared with
      the results of 32 patients in whom the focus had been removed and the defect had
      been filled with bone graft from an anterior approach, followed by stabilisation
      with CD instrumentation through an additional dorsal approach. In the cases where
      CDH instrumentation was applied, the range of fusion averaged 1.3 segments. This
      was clearly less extensive than in dorsoventral stabilisation, in which on
      average 3.5 segments were fused. In 47 of 55 cases mobilisation was achieved
      without orthesis. Eight months after the operations bony fusion could be observed
      radiologically in all patients. The mean preoperative kyphotic angle of the
      affected segments was 14.4 degrees, compared to 4 degrees after the operation.
      The mean loss of reposition was measured to be about 2.7 degrees in both groups.
      Average operation time and blood loss were about 50% higher in the patients
      treated dorsoventrally. We conclude that even in the case of florid
      spondylodiscitis, a short-range anterior fusion of the affected spinal segment
      may be performed by use of a stable-angle implant without an increased risk of
      infection-related loosening.

PMID- 9258632
TI  - Syringomyelia and Arnold Chiari in scoliosis initially classified as idiopathic:
      experience with 25 patients.
AB  - The authors analysed the clinical and radiological findings and the surgical
      management of 25 patients admitted for scoliosis classified as idiopathic at
      first presentation, but in fact associated with spinal cord and/or brain stem
      anomalies. Twenty patients had syringomyelia, 19 had Chiari malformation.
      Scoliosis was the only presenting symptom when all these patients were referred
      to the orthopaedic surgeon. On examination, five patients had normal neurological
      findings, while the others showed very mild neurological deficits. The diagnosis
      of syringomyelia and Chiari malformation was established by MRI, which is the
      best form of neuroradiological examination for discovering spinal abnormalities.
      Neurosurgical treatment is strongly recommended as the first step in the
      management of "pseudo" idiopathic scoliosis.

PMID- 9258633
TI  - Study of the course of the incidence angle during growth.
AB  - Standing posture is made possible by hip extension and lumbar lordosis. Lumbar
      lordosis is correlated with pelvic parameters, such as the declivity angle of the
      upper surface of the sacrum and the incidence angle, which determine the sagittal
      morphotype. Incidence angle, which is different for each individual, is known to
      be very important for up-right posture, but its course during life has not yet
      been established. Incidence angle was measured on radiographs of 30 fetuses, 30
      children and 30 adults, and results were analysed using the correlation
      coefficient r and Student's t test. A statistically significant correlation
      between age and incidence angle was observed. Incidence angle considerably
      increases during the first months, continues to increase during early years, and
      stabilizes around the age of 10 years. Incidence is a mark of bipedism, and its
      role in sagittal balance is essential.

PMID- 9258628
TI  - Adverse effects of class I antiarrhythmic drugs.
AB  - Class I antiarrhythmic drugs are characterised by their ability to block the fast
      inward sodium current in cardiac muscle tissue. However, at the same time, they
      can be responsible for various effects involving other organs and systems.
      Although some of these effects can be helpful in specific situations, most of
      them, such as their pro-arrhythmic propensity, are deleterious. Some of the
      adverse effects of class I antiarrhythmic drugs are directly linked to sodium
      channel blockade (conduction disorders haemodynamic perturbations, and digestive
      and neurological effects), while others are linked to other specific
      pharmacological properties (e.g. atropinic, or alpha- or beta-adrenergic
      blockade) or to nonspecific properties (idiosyncratic hypersensitivity, and
      haematological, dermatological or hepatic reactions). Other adverse effects are
      associated with complex interactions between class I antiarrhythmics and
      individual predisposing factors, trigger mechanisms and physiological factors
      (including concomitant drug treatment). These numerous variations and
      interactions within a specific environment and underlying disorder might be of
      pharmacological or/and pharmacokinetic origin, making analysis of the true
      liability of the class I drugs very difficult when adverse effects occur.

PMID- 9258634
TI  - Distribution and incidence of degenerative spine changes in patients with a lumbo
      sacral transitional vertebra.
AB  - The purpose of this prospective study was to determine the overall incidence and
      distribution of lumbo-sacral degenerative changes (i.e. disc protrusion or
      extrusion, facet degeneration, disc degeneration, nerve root canal stenosis and
      spinal stenosis) in patients with and without a lumbo-sacral transitional
      vertebra (LSTV). The study population consisted of 350 sequential patients with
      low back pain and/or sciatica, referred for medical imaging. In all cases CT
      scans of the lumbo-sacral region were obtained. In 53 subjects (15%) and LSTV was
      found. There was no difference in overall incidence of degenerative spine changes
      between the two groups. We did find, however, a different distribution pattern of
      degenerative changes between patients with and those without an LSTV. Disc
      protrusion and/or extrusion occurred more often at the level suprajacent to the
      LSTV than at the same level in patients without LSTV (45.3% vs 30.3%). This was
      also the case for disc degeneration (52.8% vs 28%), facet degeneration (60.4% vs
      42.6%) and nerve root canal stenosis (52.8% vs 27.9%). For spinal canal stenosis
      there was no statistically significant difference between the two categories. In
      conclusion, our findings indicate that an LSTV does not in itself constitute a
      risk factor for degenerative spine changes, but when degeneration occurs, it is
      more likely to be found at the disc level above the LSTV.

PMID- 9258630
TI  - Drug administration in chronic liver disease.
AB  - Cirrhosis encompasses a range of pathophysiological changes that may alter drug
      disposition. Drugs that are dependent primarily on the liver for their systemic
      clearance are more likely to be subject to reduced elimination and subsequent
      accumulation. Drug accumulation may lead to excessive plasma drug concentrations
      and adverse effects, if the adverse effects of the drug are concentration
      dependent. The effects of hepatic insufficiency on the pharmacokinetics of drugs
      are not consistent or predictable. Furthermore, the influence of hepatic disease
      on the disposition of various drugs can vary, even though those drugs may share
      the same apparent metabolic pathway. Problems in forecasting drug kinetic
      behaviour are further enhanced by the additional impairment of kidney function
      (frequently encountered in patients with advanced liver disease) and by the
      unpredictability of the glomerular filtration rate using customary methods in
      patients with cirrhosis. Accordingly, dosages are generally adapted empirically,
      with the help of serum drug concentrations, when applicable. However, drugs
      eliminated predominantly by hepatic metabolism are not among those most commonly
      inducing adverse drug reactions or causing severe complications in patients with
      cirrhosis. Electrolyte disturbances and the hepatorenal syndrome produced by
      furosemide (frusemide)-the disposition of which is not substantially modified in
      liver disease-appear to be the most frequent adverse drug reactions in patients
      with liver disease. Furthermore, clinically significant alterations in the action
      of medications at concentrations generally considered to be in the normal
      therapeutic range are not uncommon. Tissue responsiveness to the pharmacological
      action of some drugs may be modified, as evidenced by the increased
      susceptibility of the brain in patients with cirrhosis to the action of many
      psychoactive agents. Another example is the greater susceptibility of such
      patients to the nephrotoxic potential of aminogly-cosides, which should not be
      used in this patient group. Drugs may also interfere with adaptive physiological
      processes induced by liver disease. ACE inhibitors and nonsteroidal anti
      inflammatory drugs counteract the enhanced activity of the renin-angiotensin
      system in advanced liver disease, thereby generating a high risk of excessive
      hypotension or acute renal failure, respectively. These drugs are best avoided in
      patients with cirrhosis. Finally, there may be pharmacological effects that
      overlap with some pathophysiological modifications related to the process of
      liver disease, such as increased portal pressure produced by some calcium
      antagonists, or hypoprothrombinaemia related to the inhibition of synthesis of
      vitamin K-dependent clotting factors by some beta-lactam antibacterials
      (especially moxalactam and cefamandole). Accordingly, the use of these drugs
      should be avoided in advanced liver disease. It is noteworthy that reduced drug
      metabolism in patients with liver disease does not seem to have a significant
      impact on the frequency of hepatotoxicity. Special caution should be exercised,
      however, in patients with alcoholic liver disease because excessive alcohol
      intake may potentiate the hepatotoxic effect of paracetamol (acetaminophen).

PMID- 9258636
TI  - Low back pain and physical exercise in leisure time in 38-year-old men and women:
      a 25-year prospective cohort study of 640 school children.
AB  - A cohort of 38-year-old men and women were studied for leisure time physical
      exercise in relation to low back pain (LBP), education, work, social class and
      smoking by a self-administered questionnaire. At the age of 14 years, the
      subjects had been interviewed by their school doctor regarding history of LBP and
      radiographs of the thoracic and lumbar spine were taken. The results show no
      positive correlation between radiographic changes and LBP in the adolescent
      period and decreased physical activity in adulthood. Physical activity for at
      least 3 h/week reduces the risk of LBP measured as lifetime, 1-year and point
      prevalence. Eighty-five percent of the subjects who reported taking physical
      exercise for at least 3 h/week had participated in sports activity almost
      constantly since their school days and these reported being in better condition
      than the rest of the cohort. Otherwise they did not have a healthier mode of
      life. No physical exercise during leisure time was associated with a short school
      education, unskilled work, unemployment and sickness, low social class, divorce,
      living in an apartment and smoking. Sixty percent had never or not for many years
      been interested in participating in sports. Badminton and tennis were the most
      common sports practised (36%), followed by gymnastics (32%), ball games-soccer
      and team handball-(25%), running (20%) and swimming (18%). Gymnastics and
      swimming seem to reduce LBP significantly. Our results show a falling interest in
      participating in sports activities over time, with 68% of the subjects being
      members of an athletic association previously, but only 29% currently. Women were
      more physically inactive during leisure time, probably because of their dual
      role. Logistic regression analysis indicates that physical activity is related to
      a long school education, high social class and regular sports activity over time.

PMID- 9258635
TI  - Does the choice of outcome scale influence prognostic factors for lumbar disc
      surgery? A prospective, consecutive study of 121 patients.
AB  - From January to June 1994, we operated conventionally on 121 consecutive hemiated
      lumbar disc patients as part of a prospective study. We analysed general data,
      case histories, neurological findings on admission and all data from imaging
      investigations and therapy. In addition, all patients received a questionnaire
      based on the Low Back Outcome Score. Most of the patients (93%) were followed-up
      for 1 year postoperatively in the same manner. On the Prolo Scale, we obtained a
      good result in 70%; 76% had a good Low Back Outcome Score. Predictive factors are
      different for different outcome scales. The preoperative duration of pain, the
      preoperative duration of paresis and smoking seem to be general predictive
      factors.

PMID- 9258637
TI  - Temporary external fixation for low back pain: is it worth doing?
AB  - Thirty-three patients with low back pain underwent spinal fusion following a
      positively predicting external fixation test. Thirty-two spinal fusions and one
      sacroiliac joint fusion were performed. The complications following the use of
      the external fixator were significant. The results following spinal fusion were
      not related to the positive response to the external fixator. Multiple variables
      affect the results of spinal fusion. We feel that the external fixator test in
      low back pain management is very invasive, and its use cannot be justified.

PMID- 9258638
TI  - Expansive lumbar laminoplasty for degenerative spinal stenosis in patients below
      70 years of age.
AB  - We reviewed the clinical and radiological results of patients with lumbar
      degenerative spinal stenosis who underwent expansive laminoplasty with a mean
      follow-up term of 5.6 years. Twenty-seven patients underwent open-door-type
      expansive lumbar laminoplasty, which has both decompression and stabilization
      effects. Clinical results were assessed based on the score system devised by the
      Japanese Orthopaedic Association (JOA score). The number and causes of repeat
      surgery were also evaluated. Radiological changes, such as degenerative scoliosis
      and spondylolisthesis, were evaluated at the operated levels and at levels L1-L5.
      There was marked recovery of clinical symptoms assessed by pre- and postoperative
      JOA score. Nearly 80% of patients obtained good or excellent results. Only one
      patient (4%) required additional surgery, which involved discectomy at the caudal
      level of the laminoplasty. Radiographic evaluation revealed that postoperative
      changes of spondylolisthesis and scoliosis were slight both in the expanded area
      and the L1-L5 levels. Range of motion of the disc space angle in the expanded
      area showed a significant decrease postoperatively. However, pre- and
      postoperative radiological changes showed no significant correlation with JOA
      score changes and repeat surgery. In conclusion, lumbar fusion after posterior
      decompression in active patients with spinal stenosis offers satisfactory
      clinical results concomitantly with a relatively small risk of repeat surgery.

PMID- 9258639
TI  - Fusion or stabilization alone for acute distractive flexion injuries in the mid
      to lower cervical spine?
AB  - Long-term pain problems and residual restricted mobility were evaluated for
      patients sustaining acute distractive flexion injuries to the cervical spine. To
      assess which of two alternative surgical approaches gives better long-term
      outcomes, 58 patients were studied, 29 in each group. The results of posterior
      wire stabilization without fusion according to Brandt were contrasted with those
      of the Cloward technique. We found significantly more late pain problems and
      restricted neck mobility in the group treated with wiring without fusion than in
      those managed with anterior fusion. We conclude that this continuing pain may be
      due to residual mobility in the damaged degenerated non-fused motion segment, and
      that the difference between the two groups may reflect the difference in the
      quality and rate of fusion achieved by the two surgical approaches.

PMID- 9258640
TI  - Thoracolumbar hernia: a rare cause of back pain.
AB  - We report a case of a hernia through the thoracolumbar fascia in a young adult
      male who presented with pain and swelling in the thoracolumbar region. Surgical
      repair of the defect was performed in the superficial layer of the thoracolumbar
      fascia and, 18 months following surgery, he remained asymptomatic. The purpose of
      this report is to make clinicians aware of a thoracolumbar hernia as a rare cause
      of back pain.

PMID- 9258641
TI  - False aneurysm of a lumbar artery following vertebral biopsy.
AB  - Vertebral body biopsy is regarded as a simple and relatively safe technique, with
      a low complication rate. We report the case of an 80-year-old man who developed a
      false aneurysm of a lumbar artery following biopsy of the fourth lumbar vertebra.

PMID- 9258642
TI  - Spinal cord compression caused by the rod of a Harrington instrumentation device:
      a late complication in scoliosis surgery.
AB  - We report a unique complication caused by the rod of a Harrington instrumentation
      device, which resulted in spinal stenosis and myelopathy. A literature review
      revealed no previous causes of direct spinal cord impingement caused by the rod
      of a Harrington device. In this case, years after the initial operation, the rod
      penetrated the lamina at the junction between a thoracic and a lumbar curve,
      causing spinal stenosis and myelopathy. We conclude that regular control of the
      position of the device and awareness of possible late neurological complications
      are necessary to identify such complications as early as possible.

PMID- 9258643
TI  - Fracture of the thoracic spine with paralysis and esophageal perforation.
AB  - A 17-year-old young man presented with a highly unstable fracture dislocation of
      the third and fourth thoracic vertebrae with neurological deficit, in which the
      fractured spine had perforated the thoracic esophagus. Open reduction and
      internal fixation of the spinal fractures in combination with aggressive
      treatment of the mediastinitis caused by esophageal perforation, consisting of
      two re-thoracotomies, was performed. Two years after the accident, the patient
      had recovered well. The neurological deficit had recovered, and there were no
      difficulties with swallowing.

PMID- 9258644
TI  - Spinal fusion: a combined anterior and supplementary interspinous technique.
AB  - "Standard", noninstrumented, techniques of anterior interbody fusion are
      frequently followed by nonunion and collapse of the intervertebral space,
      probably because of persistent rocking movements, particularly in the sagittal
      plane. Elimination of these theoretical movements by supplementing an anterior
      interbody fusion with a posterior interspinous H-graft and a cerclage wire was
      considered to be biomechanically attractive without having the disadvantages
      associated with posterior instrumentation. In a prospective study a solid fusion
      was obtained at 16 of 17 operated levels, with a mediocre (+/- 50%) fusion as the
      exception. The height of the intervertebral space was increased at the majority
      of the fused levels. The technique is only applicable where neural arches are
      intact. The technique proved to be safe, simple, effective and inexpensive.

PMID- 9258646
TI  - Selective screening for chlamydial infection in women: a comparison of three sets
      of criteria.
AB  - Selective screening has been associated with marked declines in the prevalence of
      chlamydial infection, the most common bacterial sexually transmitted disease
      (STD) in the United States. A comparison of the performance of different
      selective screening criteria in three groups of family planning and STD clinic
      clients shows that criteria recommended by the Centers for Disease Control and
      Prevention performed well overall, detecting 88-89% of infections by screening 58
      74% of women. Criteria based on age alone performed best among low-risk clients
      with a low prevalence of chlamydial infection, particularly when all women
      younger than age 25 were screened (sensitivity, 84-92%); the age-based criteria
      still required screening only 59-71% of all women. Selective screening criteria
      should be based on age, risk profile and chlamydia prevalence in specific
      clinical settings, and should be reevaluated as chlamydia prevalence declines.

PMID- 9258645
TI  - Men's behavior change following infection with a sexually transmitted disease.
AB  - An analysis of data on 20-39-year-old men participating in the 1991 National
      Survey of Men finds that of 466 respondents who had ever had a sexually
      transmitted disease (STD), 25% had sex while infected. However, 85% of these men
      informed their partner of their infection before having intercourse. Black men
      were significantly less likely than whites to have had sex while infected.
      Overall, 29% of men with an STD did not modify their sexual behavior or condom
      use. Blacks, married men and men who were affiliated with a religious group were
      less likely than whites, single men and those with no religious affiliation to
      maintain the same behavior subsequent to the diagnosis of an STD infection as
      before. Black men were more likely than whites to start using condoms; blacks,
      religious men, less-educated men and those who were older when they had their
      first sexual experience were the most likely to stop having sex with casual
      partners once they learned that they were infected with an STD.

PMID- 9258647
TI  - Screening criteria for Chlamydia trachomatis in family planning clinics:
      accounting for prevalence and clients' characteristics.
AB  - The reliability of eight self-reported risk factors as criteria for screening
      women for Chlamydia trachomatis was evaluated in four family planning clinics in
      New York State that serve diverse populations. In all, 8,920 women were screened
      in these clinics; the rates of infection ranged from 2% to 7%. Results of
      multivariate analyses showed that age was the most important predictor of
      chlamydial infection in the three clinics where prevalence was 4% or higher;
      women aged 20-24 were 3-4 times as likely as older women to be infected, and
      those aged 13-19 were 4-6 times as likely. In these three clinics, screening all
      women aged 26 or younger (62-80% of the clinic population) would identify about
      90% of infected women; in the clinic with the lowest prevalence rate, age was not
      a reliable criterion. The prevalence of self-reported risk factors varied by
      clinic, and these factors generally were not reliable indicators of infection.
      Using the presence of at least one self-reported risk factor as a screening
      criterion, 80-87% of clinic clients would be screened, and about 90% of infected
      women would be identified. The presence of clinical signs of chlamydial infection
      does not increase the reliability of age as a screening criterion.

PMID- 9258649
TI  - Pregnancy prevention among urban adolescents younger than 15: results of the 'In
      Your Face' program.
AB  - Data from a pregnancy prevention program operating through school-based clinics
      in four New York City junior high schools suggest that an intensive risk
      identification and case-management approach may be effective among very young
      adolescents. Among students given a referral to a family planning clinic for
      contraception, the proportion who visited the clinic and obtained a method rose
      from 11% in the year before the program began to 76% in the program's third year.
      Pregnancy rates among teenagers younger than 15 decreased by 34% over four years
      in the program schools. In the fourth year of the program, the pregnancy rate in
      one school that was unable to continue the program was almost three times the
      average rate for the other three schools (16.5 pregnancies per 1,000 female
      students vs. 5.8 per 1,000).

PMID- 9258648
TI  - Urban adolescent females' views on the implant and contraceptive decision-making:
      a double paradox.
AB  - Focus groups and in-depth interviews were used to explore the decline in
      popularity of the contraceptive implant in a clinic-based sample of 41 ethnically
      diverse, urban, sexually active adolescents. While these teenagers' socioeconomic
      status and patterns of inconsistent contraceptive use made them potentially ideal
      implant recipients, they were unlikely to select this method. Negative media
      reports about the method were less influential than social conditions such as
      peer perspectives and gender relations. Oral networks that propagated
      misinformation went unchallenged because of the silence of satisfied users.
      Personal factors such as future orientation, autonomous decision-making and value
      of control also influenced contraceptive decision-making.

PMID- 9258650
TI  - The measurement of public opinion on abortion: the effects of survey design.
AB  - A factorial experiment examined the effects of the wording and sequence of survey
      questions on the measurement of attitudes toward abortion. When a first-trimester
      pregnancy is specified, 55% of respondents agree that a woman should be able to
      obtain a legal abortion for any reason, compared with 44% when no pregnancy
      duration is stated. Specifying first-trimester pregnancies has little effect on
      the proportion of respondents who agree that abortion should be available for
      maternal health, fetal defects or rape, but it significantly increases the
      proportion who agree that a woman should be able to obtain an abortion if she is
      single, has financial constraints or wants no more children. When gestational
      lengths from one to six months are presented to respondents in ascending order,
      agreement that a woman should be able to obtain an abortion for any reason is
      lower for any given length of gestation than when pregnancy durations are
      presented in descending order. Forty-eight percent of respondents agree that
      abortion should be legal for any reason when that question is posed after a
      series of specific reasons; however, 60% do so when it is the first question in
      the sequence. The difference in agreement with abortion for any reason between
      Catholics and non-Baptist Protestants, and between Republicans and Democrats, is
      much smaller when the question is asked first than when it is presented last.

PMID- 9258653
TI  - The Colorado Parental Rights Amendment: how and why it failed.

PMID- 9258651
TI  - Factors associated with use of the female condom.
AB  - Black, Hispanic and white women recruited for an HIV prevention intervention were
      instructed in the use of the female condom and encouraged to try the device. Of
      the 231 women who completed the intervention, 29% tried the condom over the
      course of a month; 30% of those who tried it used it during at least half of
      their sexual encounters. Both ethnicity and age were associated with trying the
      device: Nearly 40% of black women and 30% of Hispanic women did so, compared with
      18% of white women; 37% of those aged 25-34 tried the female condom, compared
      with 22% of women younger than 25. Trying the device was more likely among women
      living with a partner, those with a history of sexually transmitted disease
      infection, women who had had an HIV test, those who did not believe that the
      method afforded them a greater degree of overall control than did the male condom
      and those who had no prior knowledge of the device. Among women who used the
      device during at least half of their sexual encounters, 27% were black and 44%
      were Hispanic: 38% were younger than 25, and 43% were single. More regular users
      were about half as likely as less regular users to experience difficulty with
      insertion and one-eighth as likely to report the device slipping during use; they
      were more likely than less regular users to report that sex was more pleasurable
      with the female condom than with the male condom.

PMID- 9258652
TI  - Increasing the availability of vasectomy in public-sector clinics.
AB  - A program designed to improve the availability of vasectomy in public-sector
      clinics trained physicians at 43 facilities in no-scalpel vasectomy between 1993
      and 1995. Among the 38 clinics that responded to a follow-up survey in 1996, the
      number of clinics providing vasectomies rose from 23 to 32, an increase of almost
      40%, while the number of vasectomies performed rose by 18%. Seventeen of the 32
      clinics performed more vasectomies after the training; 10 of the 17 had not
      previously provided the procedure. In-depth interviews with staff from seven
      sites that experienced large caseload increases and from seven that experienced
      decreases identified three elements for the successful establishment or expansion
      of vasectomy services-sufficient numbers of trained providers, funds to subsidize
      vasectomies for men who cannot afford them and activities to raise awareness
      about the availability of low-cost or free vasectomy.

PMID- 9258654
TI  - Sustained nontumorigenic phenotype correlates with a largely stable chromosome
      content during long-term culture of the human keratinocyte line HaCaT.
AB  - Altered growth and differentiation and a highly abnormal karyotype are generally
      believed to be indicators for tumorigenic conversion of human cells. Inactivation
      of TP53 is supposedly one possible mechanism for accelerated genetic aberrations
      via reduced control of the genetic integrity. To examine the significance of this
      functional relationship, we investigated the long-term development of the
      spontaneously immortalized human skin keratinocyte line HaCaT, carrying UV
      specific mutations in both alleles of the TP53 tumor suppressor gene. During >
      300 passages, proliferation, clonogenicity, and serum-independent growth
      potential increased. In addition, HaCaT cells gained anchorage independence and
      at late passages showed reduced differentiation. Karyotypic analysis up to
      passage 225 revealed a high frequency of translocations and deletions, with a
      particular increase during passages 30 and 50. Nevertheless, the HaCaT cells
      remained nontumorigenic when injected subcutaneously, and noninvasive in surface
      transplants in nude mice. By comparative genomic hybridization, we confirmed the
      karyotypically identified phase of increased chromosomal aberrations between
      passages 30 and 50. However, before and thereafter, the CGH profiles of the
      individual chromosomes were largely unchanged, demonstrating that those
      translocations-also maintained in later passages-did not cause a gross
      chromosomal imbalance. Thus, our data suggest that multiple changes often
      correlated with a "transformed phenotype," including extensive karyotypic
      alterations and mutational inactivation of TP53, are well compatible with a
      nontumorigenic phenotype of the HaCaT cells, and that preserved chromosomal
      balance may be crucial for this stability during long-term propagation.

PMID- 9258655
TI  - Variable FHIT transcripts in non-neoplastic tissues.
AB  - We used nested reverse transcriptase PCR to investigate the expression of the
      FHIT gene, a presumptive tumor suppressor gene located in chromosomal band 3p
      14.2, in non-neoplastic samples. Multiple transcripts of the FHIT gene were found
      in peripheral blood lymphocytes, skeletal muscle, and liver of healthy
      individuals, as well as in a cell line derived from isynovial tissue. The data
      indicate that variable splicing of the FHIT transcript, leading to deletions of
      exons and thus anomalous or absent FHIT protein production, occurs frequently in
      non-neoplastic tissues. Hence, the finding of multiple nonfunctional FHIT
      transcripts is not tumor-specific and cannot be used as a genetic marker of
      neoplasia.

PMID- 9258656
TI  - Normal FHIT transcripts in renal cell cancer- and lung cancer-derived cell lines,
      including a cell line with a homozygous deletion in the FRA3B region.
AB  - The recently identified FHIT gene encompasses the FRA3B region and the breakpoint
      of a constitutive t(3;8) occurring in a family with hereditary renal cell cancer.
      Occurrence of aberrant transcripts in different types of tumours has led to the
      suggestion that FHIT might play a critical role in the development of various
      types of cancer. We have analyzed the gene and its transcripts in lung cancers
      and renal cell cancer-derived cell lines. A lung adenocarcinoma cell line, GLC
      A2, appeared to have a homozygous deletion in intron 5 of FHIT. RT-PCR analysis
      revealed a normal-sized PCR product in all of the cell lines: Including GLC-A2. A
      number of them had an additional aberrant product. Analysis of a great number of
      control cell lines and tissues showed that the majority of these also had
      aberrant PCR products in addition to a normal-sized PCR product. Different
      specimens of the same cell type showed variable additional RT-PCR products.
      Normal-sized PCR products had a sequence identical to the FHIT sequence. PCR
      products longer than normal had insertions of different sizes at different
      positions. With three exceptions, PCR products shorter than normal represented
      FHIT sequences missing one or more entire exons. Thus, the presence of aberrant
      transcripts is not cancer-specific. Conceivably, sequence responsible for the
      instability of the FRA3B region are being transcribed into FHIT pre-mRNA and may
      cause the abnormal splicing and processing of the transcripts.

PMID- 9258657
TI  - Analysis of multiple renal cell adenomas and carcinomas suggests allelic loss at
      3p21 to be a prerequisite for malignant development.
AB  - Multiple renal cell tumours from three unrelated patients have been analysed for
      loss of heterozygosity of 3p, mutation of VHL, and chromosome 7 and 17
      imbalances. Loss of 3p alleles is characteristic for clear cell type tumours and
      the combination of +7, +17 for chromophilic cell type tumours. Thus, we could
      classify adenomas and carcinomas of the three patients according to the genomic
      patterns of the tumours. Adenomas appeared to be mostly of the chromophilic cell
      type. In some adenomas, however, allelic losses of chromosome 3 were detected,
      pointing to a clear cell phenotype. Irrespective of showing loss or retention of
      the 3p25 region, none of the adenomas had a VHL mutation. Therefore, inactivation
      of VHL does not seem to be an early event in the development of renal cell
      tumours. Results of an analysis of regions of loss and retention of alleles of 3p
      markers in multiple tumours of the individual patients suggest that losses at
      either 3p25 or 3p12-p14 are associated with adenomas. Additional loss at 3p21 is
      most likely required to lead to development of a more malignant clear cell
      carcinoma.

PMID- 9258658
TI  - Advanced-stage cervical carcinomas are defined by a recurrent pattern of
      chromosomal aberrations revealing high genetic instability and a consistent gain
      of chromosome arm 3q.
AB  - We have analyzed 30 cases of advanced-stage cervical squamous cell carcinoma
      (stages IIb-IV) by comparative genomic hybridization (CGH). The most consistent
      chromosomal gain in the aneuploid tumors was mapped to chromosome arm 3q in 77%
      of the cases. Acquisition of genetic material also occurred frequently on Iq
      (47%), 5p (30%), 6p (27%), and 20 (23%). Recurrent losses were mapped on 2q
      (33%), 3p (50%), 4 (33%), 8p (23%), and 13q (27%). High-level copy number
      increases were mapped to chromosome 8, chromosome arms 3q, 5p, 8q, 12p, 14q, 17q,
      19q, 20p, and 20q, and chromosomal bands 3q26-27, 9p23-24, 11q22-23, and 12p13.
      In the majority of the cases, the presence of high-risk human papilloma virus
      genomes was detected. High proliferative activity was accompanied by crude
      aneuploidy. Increased p21/WAF-I activity, but low or undetectable expression of
      TP53 were representative for the immunophenotype. This study confirms the
      importance of a gain of chromosome arm 3q in cervical carcinogenesis and
      identifies additional, recurrent chromosomal aberrations that are required for
      progression from stage I tumors to advanced-stage carcinomas.

PMID- 9258659
TI  - Linkage analysis of familial melanoma and chromosome 6 in 14 Australian kindreds.
AB  - CDKN2A (9p21) and CDK4 (12q13) have been identified as melanoma susceptibility
      genes in certain familial melanoma (FM) kindreds. There remain other FM families,
      however, for which there is little or no evidence for linkage of melanoma to
      these loci. Other loci may be involved in susceptibility to this malignancy.
      Chromosome 6 is deleted or rearranged in 66% of melanomas and has been targeted
      by several studies in an attempt to identify chromosomal regions associated with
      initiation or progression of melanoma. Previous studies of familial melanoma and
      chromosome arm 6p reported evidence suggestive of linkage for markers flanking
      the HLA complex. We have carried out genetic linkage analysis in 14 Australian
      familial melanoma kindreds using 16 short tandem repeat polymorphism (STRP)
      markers spanning 6p23-6q27. Analysis by maximum likelihood and non-parametric
      (affected pedigree member) techniques showed no evidence of linkage of melanoma
      in this family set to chromosome 6 (two-point Zmax = 0.5 at theta = 0.2 for
      D6S285). Lod scores > 1.0 were obtained for the loci D6S285, D6S105, D6S265,
      D6S292, and D6S311 in three individual kindreds but these were insufficiently
      strong for formal heterogeneity testing to confirm that a chromosome 6-linked
      subset of families exists. These data imply little or no role for a major
      chromosome 6 melanoma susceptibility locus; however the possibility of such a
      locus remains open and warrants further investigation.

PMID- 9258660
TI  - Genetic lesions associated with blastic transformation of polycythemia vera and
      essential thrombocythemia.
AB  - Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic
      myeloproliferative disorders that may progress to acute leukemia in a subset of
      patients. This study aimed at investigating the genetic lesions associated with
      the blastic transformation of PV and ET. A panel of PV and ET cases at different
      stages of disease was analyzed for the presence of genetic alterations of TP53,
      NRAS, KRAS, and MDM2 by a combination of mutational analysis and Southern blot
      hybridization. The occurrence of microsatellite instability (MSI) was also tasted
      in selected cases. Samples of PV and ET analyzed in chronic phase disease were
      consistently devoid of all genetic lesions tested, suggesting that alterations of
      TP53, NRAS, KRAS, and MDM2 do not contribute significantly to development of
      chronic phase PV and ET. Conversely, mutations of TP53 were detected in 7/15
      (46.6%) blastic phase cases, including 3/5 PV and 4/10 ET. In blastic phase
      patients for whom the corresponding chronic phase DNA was also available, it
      could be documented that the genetic lesion had arisen at the time of blastic
      transformation. In addition to TP53 mutations, cases of blastic phase PV and ET
      occasionally harbored mutations of NRAS (one case of blastic phase ET) or
      displayed MSI (one case of blastic phase PV). These data indicate that
      inactivation of TP53 is a relatively frequent event associated with the blastic
      transformation of PV and ET and may be responsible for the tumor progression of
      these disorders.

PMID- 9258661
TI  - Differential splicing of exon 5 of the Wilms tumour (WTI) gene.
AB  - The WTI gene encodes a developmentally regulated transcription factor whose
      function is altered by alternative splicing at two sites: the 17 amino acids of
      exon 5, whose functional effects are ill-defined, and the 3 amino acids (KTS)
      between exons 9 and 10, which determine sequence-specific DNA binding and nuclear
      localisation. Germline mutations, which prevent normal KTS splicing, can underlie
      the Denys-Drash syndrome, and disruptions of splicing of exon 5 may occur in
      Wilms tumours. We analysed by reverse transcriptase polymerase chain reaction (RT
      PCR) amplification the relative ratios of the four splice variants of WTI mRNA in
      normal and tumour tissues and found tissue-specific, developmental stage
      specific, and species-specific differences in the splicing of exon 5 but not of
      KTS. We found no evidence for disrupted splicing in acute leukaemias or gonadal
      tumours. The significance of these findings is discussed, and the possibility is
      raised that WTI may orchestrate the appropriate response to growth and
      differentiation factor signalling, mediated by alterations in the relative levels
      of exon 5 containing WTI isoforms.

PMID- 9258662
TI  - Genetic alterations in primary breast cancers and their metastases: direct
      comparison using modified comparative genomic hybridization.
AB  - Breast tumor development and progression are thought to be driven by an
      accumulation of genetic alterations, but little is known about the specific
      changes that occur during the metastatic process. We analyzed pairs of primary
      breast cancers and their matched lymph node metastases from 11 patients, pairs of
      primaries and distant metastases from three patients, and pairs of primaries, and
      local recurrences from two patients by using comparative genomic hybridization
      (CGH). Simultaneous hybridization analysis of primary versus matched lesion DNAs
      from 11 patients was also performed (modified CGH). This modified approach was
      useful not only for confirming CGH results but also for demonstrating
      quantitative differences between aberrations present at both sites. Frequent
      chromosomal changes present at both sites (> 35% of 16 cases) were 1q, 8q, and
      17q gains and 6q, 8p, 9q, 13q, 16q, 17p, and Xp losses. The total number of
      aberrations detected exclusively in the lymph nodes or distant metastases was
      higher than that in the primary tumors (2.5 vs. 0.7, P < 0.05). We found high
      level amplifications in four metastases (two lymph nodes and two distant
      metastases), but none in any primary tumor. These findings suggest that
      progression from primary breast cancer to metastasis may be associated with the
      acquisition of further genetic changes. Although further investigations are
      required, it was of interest that 3 of 11 patients (27%) showed 18q loss solely
      in their lymph node metastases.

PMID- 9258663
TI  - FISH analysis of translocations involving the short arm of chromosome 9 in
      lymphoid malignancies.
AB  - Deletion of the short arm of chromosome 9 (9p), resulting in the loss of the
      p16INK4a/MTS1 gene, now called CDKN2, has been found to occur frequently in acute
      lymphoblastic leukemia, even in the absence of a microscopically visible
      deletion. In this study, we have used YAC probes encompassing the CDKN2 locus to
      analyze by fluorescence in situ hybridization patients with leukemia and lymphoma
      and translocations involving 9p in order to establish the CDKN2 status in
      relation to the karyotype. We found that, in leukemic cells exhibiting loss of
      heterozygosity at the CDKN2 locus, the deleted allele was from the
      cytogenetically normal chromosome 9, whereas the other allele was located on a
      rearranged chromosome. This finding suggests that CDKN2 gene loss is nonrandomly
      associated with 9p translocation in lymphoid proliferations. Genes Chromosom.

PMID- 9258664
TI  - Increased chromosome 20 copy number detected by fluorescence in situ
      hybridization (FISH) in malignant melanoma.
AB  - DNA amplification is an important mechanism of tumor progression that allows
      cancer cells to up-regulate the expression of critical genes such as oncogenes
      and genes conferring drug resistance. Recent studies using comparative genomic
      hybridization (CGH) revealed increased DNA copies of 20q sequences in 7 melanoma
      cell lines and B archival metastatic melanoma lesions. To evaluate chromosome 20
      abnormalities in more detail and to resolve discrepancies between karyotype and
      CGH findings, we performed FISH analysis of metaphase cells in 13 melanoma cell
      lines (including the 7 lines used for CGH) and 9 primary melanoma specimens by
      using a whole chromosome paint specific for chromosome 20. All 13 cell lines
      (100%) and 8/9 primary tumors (89%) showed extra copies of chromosome 20 relative
      to tumor ploidy. Additionally, 6/14 cell lines (43%) and 2/8 primary tumors (25%)
      showed translocated chromosome 20 material previously undetected by standard
      cytogenetics. Cytologic evidence for gene amplification was also found in one
      cell line, which contained an add(20)(p13), with additional DNA being derived
      from 20q sequences. These data suggest that overrepresentation of a gene or genes
      important for melanoma pathogenesis resides on the long arm of chromosome 20.

PMID- 9258665
TI  - Frequent loss of the 11q14-24 region in chronic lymphocytic leukemia: a study by
      comparative genomic hybridization. Tampere CLL Group.
AB  - The genetic basis and molecular pathogenesis of chronic lymphocytic leukemia
      (CLL) and the molecular mechanisms responsible for its progression remain poorly
      understood. Here, karyotyping techniques specifically optimized for CLL,
      comparative genomic hybridization (CGH), and fluorescence in situ hybridization
      were used to search for CLL-specific genetic aberrations. CGH and karyotyping
      both revealed copy number changes in 12 of the 25 CLL cases (48%) analyzed. Loss
      at 11q emerged as the most common aberration (6 cases), followed by a gain of
      chromosome 12 (4) and loss at 13q (3). Concordance between CGH and G-banding was
      found in 23 of the 25 cases (92%), which is more than reported in a recent
      similar CGH study of CLL. Owing to the basic differences in G-banding and CGH,
      however, their simultaneous clinical application is recommended. The frequent
      loss of 11q14-24 suggests that this chromosomal region deserves further attention
      as a candidate locus involved in the pathogenesis of CLL.

PMID- 9258666
TI  - The first recurring chromosome translocation in hepatoblastoma:
      der(4)t(1;4)(q12;q34).
AB  - We report four cases of hepatoblastoma with a derivative chromosome 4 from an
      unbalanced translocation between the long arms of chromosomes 1 and 4, an
      aberration reported only rarely in isolated cases of other types of neoplasms.
      The abnormality in three hepatoblastomas was der(4)t(1;4)(q12;q34), whereas the
      fourth case appeared to have a der(4)t(q25;q32). All had hyperdiploid tumor
      karyotypes; however, in the case with t(q25;q32), the der(4) was the only
      abnormality in the stemline. We speculate that the oncogenetic event in our cases
      may be the loss of a gene on distal 4q or their alteration by juxtaposition to
      1q12 heterochromatin.

PMID- 9258667
TI  - The value of basic research: discovery of Thermus aquaticus and other extreme
      thermophiles.

PMID- 9258668
TI  - Megaplasmid and chromosomal loci for the PHB degradation pathway in Rhizobium
      (Sinorhizobium) meliloti.
AB  - Chromosomal and megaplasmid loci that affect the poly-3-hydroxybutyrate (PHB)
      degradation pathway in Rhizobium meliloti were identified. A clone that restores
      the ability of certain R. meliloti mutants with defined deletions in megaplasmid
      pRmeSU47b to use 3-hydroxybutyrate or acetoacetate as the sole carbon source was
      isolated from a cosmid library of R. meliloti genomic DNA. Tn5 insertion
      mutagenesis, followed by merodiploid complementation analysis, demonstrated that
      the locus consists of at least four transcriptional units, bhbA-D. We also
      identified loci involved in 3-hydroxybutyrate and/or acetoacetate utilization by
      screening for mutants that had lost the ability to use 3-hydroxybutyrate as the
      sole carbon source while retaining the ability to use acetate (thus ensuring an
      intact glyoxylate cycle and gluconeogenic pathway). These mutants fell into four
      classes, as determined by replicon mobilization experiments and genetic linkage
      in phage transduction; one class corresponded to the bhb locus on pRmeSU47b, two
      classes mapped to different regions on the chromosome and the fourth, bdhA,
      represented by a single mutant, mapped to another pRmeSU47b locus, near bacA. The
      bdhA mutant is deficient in 3-hydroxybutrate dehydrogenase activity.

PMID- 9258669
TI  - A recombinationally repressed region between mat2 and mat3 loci shares homology
      to centromeric repeats and regulates directionality of mating-type switching in
      fission yeast.
AB  - Cells of the fission yeast Schizosaccharomyces pombe switch mating type by
      replacing genetic information at the transcriptionally active mat1 locus with
      sequences copied from one of two closely linked silent loci, mat2-P or mat3-M. By
      a process referred to as directionality of switching, cells predominantly switch
      to the opposite mat1 allele; the mat1-P allele preferentially recombines with
      mat3, while mat1-M selects the mat2. In contrast to efficient recombination at
      mat1, recombination within the adjoining mat2-mat3 interval is undetectable. We
      defined the role of sequences between mat2 and mat3, designated the K-region, in
      directionality as well as recombinational suppression. Cloning and sequencing
      analysis revealed that a part of the K-region is homologous to repeat sequences
      present at centromeres, which also display transcriptional and recombinational
      suppression. Replacement of 7.5 kb of the K-region with the ura4+ gene affected
      directionality in a variegated manner. Analysis of the swi6-mod locus, which was
      previously shown to affect directionality, in K delta::ura4+ strains suggested
      the existence of at least two overlapping directionality mechanisms. Our work
      furthers the model that directionality is regulated by cell-type-specific
      organization of the heterochromatin-like structure in the mating-type region and
      provides evidence that the K-region contributes to silencing of the mat2-mat3
      interval.

PMID- 9258670
TI  - Involvement of the yeast DNA polymerase delta in DNA repair in vivo.
AB  - The POL3 encoded catalytic subunit of DNA polymerase delta possesses a highly
      conserved C-terminal cysteine-rich domain in Saccharomyces cerevisiae. Mutations
      in some of its cysteine codons display a lethal phenotype, which demonstrates an
      essential function of this domain. The thermosensitive mutant pol3-13, in which a
      serine replaces a cysteine of this domain, exhibits a range of defects in DNA
      repair, such as hypersensitivity to different DNA-damaging agents and deficiency
      for induced mutagenesis and for recombination. These phenotypes are observed at
      24 degrees, a temperature at which DNA replication is almost normal; this
      differentiates the functions of POL3 in DNA repair and DNA replication. Since
      spontaneous mutagenesis and spontaneous recombination are efficient in pol3-13,
      we propose that POL3 plays an important role in DNA repair after irradiation,
      particularly in the error-prone and recombinational pathways. Extragenic
      suppressors of pol3-13 are allelic to sdp5-1, previously identified as an
      extragenic suppressor of pol3-11. SDP5, which is identical to HYS2, encodes a
      protein homologous to the p50 subunit of bovine and human DNA polymerase delta.
      SDP5 is most probably the p55 subunit of Pol delta of S. cerevisiae and seems to
      be associated with the catalytic subunit for both DNA replication and DNA repair.

PMID- 9258671
TI  - A WD repeat protein, Rec14, essential for meiotic recombination in
      Schizosaccharomyces pombe.
AB  - Mutations in the Schizosaccharomyces pombe rec14 gene reduce meiotic
      recombination by as much as a factor of 1000 in the three intervals tested on
      chromosomes I and III. A DNA clone complementing the rec14 mutation was shown by
      genetic and physical analysis to contain the rec14 gene, which was functional in
      plasmid-borne inserts as small as 1.4 kb. The rec14 gene contains two exons
      separated by a 53-bp intron, which was confirmed by analysis of rec14
      transcripts. The spliced transcript encodes a protein product of 302 amino acids,
      which contains six WD repeat motifs found in the G-beta transducin family of
      proteins and other proteins, including the Saccharomyces cerevisiae Ski8 (Rec103)
      protein. Although the rec14 transcripts were present in mitotically dividing
      cells, rec14 mutations had no detectable effect on mitotic recombination. The
      pattern of expression of rec14 differes from that of previously analyzed S. pombe
      rec genes. Based upon mutant phenotypes and amino acid sequence similarities, we
      propose that S. pombe Rec14 is a functional homologue of S. cerevisiae Rec103.

PMID- 9258672
TI  - Molecular and genetic analysis of REC103, an early meiotic recombination gene in
      yeast.
AB  - In the yeast Saccharomyces cerevisiae at least 10 genes are required to begin
      meiotic recombination. A new early recombination gene REC103 is described in this
      paper. It was initially defined by the rec103-1 mutation found in a selection for
      mutations overcoming the spore inviability of a rad52 spo13 haploid strain.
      Mutations in REC103 also rescue rad52 in spo13 diploids. rec103 spo13 strains
      produce viable spores; these spores show no evidence of meiotic recombination.
      rec103 SPO13 diploids produce no viable spores, consistent with loss of
      recombination. Mutations in REC103 do not affect mitotic recombination, growth,
      or repair. These phenotypes are identical to those conferred by mutations in
      several other early meiotic recombination genes (e.g., REC102, REC104, REC114,
      ME14, MER2, and SPO11). REC103 maps to chromosome VII between ADE5 and RAD54.
      Cloning and sequencing of REC103 reveals that REC103 is identical to SK18, a gene
      that depresses the expression of yeast double-stranded ("killer") (ds)RNA
      viruses. REC103/SK18 is transcribed in mitotic cells and is induced approximately
      15-fold in meiosis. REC103 has 26% amino acid identity to the Schizasaccharomyces
      pombe rec14+ gene; mutations in both genes confer similar meiotic phenotypes,
      suggesting that they may play similar roles in meiotic recombination.

PMID- 9258673
TI  - Mismatch repair in Schizosaccharomyces pombe requires the mutL homologous gene
      pms1: molecular cloning and functional analysis.
AB  - Homologues of the bacterial mutS and mutL genes involved in DNA mismatch repair
      have been found in organisms from bacteria to humans. Here, we describe the
      structure and function of a newly identified Schizosaccharomyces pombe that
      encodes a predicted amino acid sequence of 794 residues with a high degree of
      homology to MutL related proteins. On the basis of its closer relationship to the
      eukaryotic "PMS" genes than to the "MLH" genes, we have designated the S. pombe
      homologue pms1. Disruption of the pms1 gene causes a significant increase of
      spontaneous mutagenesis as documented by reversion rate measurements. Tetrad
      analyses of crosses homozygous for the pms1 mutation reveal a reduction of spore
      viability from > 92% to 80% associated with a low proportion (approximately 50%)
      of meioses producing four viable spores and a significant, allele-dependent
      increase of the level of post-meiotic segregation of genetic marker allele pairs.
      The mutant phenotypes are consistent with a general function of pms1 in
      correction of mismatched base pairs arising as a consequence of DNA polymerase
      errors during DNA synthesis, or of hybrid DNA formation between homologous but
      not perfectly complementary DNA strands during meiotic recombination.

PMID- 9258674
TI  - Constitutive mutations of the Saccharomyces cerevisiae MAL-activator genes MAL23,
      MAL43, MAL63, and mal64.
AB  - We report the sequence of several MAL-activator genes, including inducible,
      constitutive, and noninducible alleles of MAL23, MAL43, MAL63, and mal64.
      Constitutive alleles of MAL23 and MAL43 vary considerably from inducible alleles
      in their C-terminal domain, with many of the alterations clustered and common to
      both alleles. The 27 alterations from residues 238-461 of Mal43-C protein are
      sufficient for constitutivity, but the minimal number of alterations needed for
      the constitutive phenotype could not be determined. The sequence of mal64, a
      nonfunctional homologue of MAL63, revealed that Mal64p is 85% identical to
      Mal63p. Two mutations that activate mal64 and cause constitutivity are nonsense
      mutations resulting in truncated proteins of 306 and 282 residues. We conclude
      that the C-terminal region of the MAL-activator, from residues 283-470, contains
      a maltose-responsive negative regulatory domain, and that extensive mutation or
      deletion of the entire region causes loss of the negative regulatory function.
      Additionally, certain sequence elements in the region appear to be necessary for
      efficient induction of the full-length Mal63 activator protein. These studies
      highlight the role of ectopic recombination as an important mechanism of
      mutagenesis of the telomere-associated family of MAL loci.

PMID- 9258676
TI  - Genetic analysis of parasitism in the soybean cyst nematode Heterodera glycines.
AB  - A genetic analysis of parasitic ability in the soybean cyst nematode Heterodera
      glycines was performed. To identify and characterize genes involved in
      parasitism, we developed three highly inbred H. glycines lines, OP20, OP25 and
      OP50, for use as parents for controlled crosses. Through these crosses, we have
      identified genes in the inbred parents that control reproduction of the nematode
      on hosts that carry resistance genes. These genes, designated as ror-* for
      reproduction on a resistant host, segregate in a normal Mendelian fashion as
      independent loci. Host range tests of F1 generation progeny indicated that at
      least one parasitism gene in both the OP20 and OP50 lines for host PI 88788 was
      dominant. Parasitism genes in OP50 for hosts "Peking" and PI 90763 are recessive.
      Two types of single female descent populations, a single backcrossed BC1F2
      derived and a double backcrossed BC2F1-derived, were established on the
      susceptible soybean cultivar "Lee 68." Host range tests for parasitism in these
      lines demonstrated the presence of two independent genes in OP50, one for host PI
      88788 designated ror-1 and one for host PI 90763 designated ror-2. OP20 carries
      two independent genes for parasitism on PI 88788, designated as alleles kr3 and
      kr4.

PMID- 9258677
TI  - Mutational analysis of the Drosophila sister-chromatid cohesion protein ORD and
      its role in the maintenance of centromeric cohesion.
AB  - The ord gene is required for proper segregation of all chromosomes in both male
      and female Drosophila meiosis. Here we describe the isolation of a null ord
      allele and examine the consequences of ablating ord function. Cytologically,
      meiotic sister-chromatid cohesion is severely disrupted in flies lacking ORD
      protein. Moreover, the frequency of missegregation in genetic tests is consistent
      with random segregation of chromosomes through both meiotic divisions, suggesting
      that sister cohesion may be completely abolished. However, only a slight decrease
      in viability is observed for ord null flies, indicating that ORD function is not
      essential for cohesion during somatic mitosis. In addition, we do not observe
      perturbation of germ-line mitotic divisions in flies lacking ORD activity. Our
      analysis of weaker ord alleles suggests that ORD is required for proper
      centromeric cohesion after arm cohesion is released at the metaphase I/anaphase I
      transition. Finally, although meiotic cohesion is abolished in the ord null fly,
      chromosome loss is not appreciable. Therefore, ORD activity appears to promote
      centromeric cohesion during meiosis II but is not essential for kinetochore
      function during anaphase.

PMID- 9258675
TI  - Allelic specificity at the het-c heterokaryon incompatibility locus of Neurospora
      crassa is determined by a highly variable domain.
AB  - In filamentous fungi, the ability to form a productive heterokaryon with a
      genetically dissimilar individual is controlled by specific loci termed het loci.
      Only strains homozygous for all het loci can establish a heterokaryon. In
      Neurospora crassa, 11 loci, including the mating-type locus, regulate the
      capacity to form heterokaryons. An allele of the het-c locus (het-cOR) of N.
      crassa has been previously characterized and encodes a nonessential 966 amino
      acid glycine-rich protein. Herein, we describe the genetic and molecular
      characterization of two hei-c alleles, het-cPA and het-cOR, that have a different
      specificity from that of het-cOR, showing that vegetative incompatibility is
      mediated by multiple alleles at het-c. By constructing chimeric alleles, we show
      that het-c specificity is determined by a highly variable domain of 34-48 amino
      acids in length. In this regard, het-c is similar to loci that regulate
      recognition in other species, such as the (S) self-incompatibility locus in
      plants, the sexual compatibility locus in basidiomycetes and the major
      histocompatibility complex (MHC) genes in vertebrates.

PMID- 9258678
TI  - Evidence for an inducible repair-recombination system in the female germ line of
      Drosophila melanogaster. III. Correlation between reactivity levels, crossover
      frequency and repair efficiency.
AB  - We previously reported evidence that the so-called reactivity level, a peculiar
      cellular state of oocytes that regulates the frequency of transposition of I
      factor, a LINE element-like retrotransposon, might be one manifestation of a DNA
      repair system. In this article, we report data showing that the reactivity level
      is correlated with the frequency of crossing over, at least on the X chromosome
      and on the pericentromeric region of the third chromosome. Moreover, a check for
      X-chromosome losses and recessive lethals produced after gamma irradiation in
      flies with different reactivity levels, but common genetic backgrounds, brings
      more precise evidence for the relationship between reactivity levels and DNA
      repair. Those results support the existence of a repair-recombination system
      whose efficiency is modulated by endogenous and environmental factors. The
      implications of this biological system in connecting genomic variability and
      environment may shed new lights on adaptative mechanisms. We propose to call it
      VAMOS for variability modulation system.

PMID- 9258679
TI  - The vrille gene of Drosophila is a maternal enhancer of decapentaplegic and
      encodes a new member of the bZIP family of transcription factors.
AB  - We report here the genetical and molecular characterization of a new Drosophila
      zygotic lethal locus, vrille (vri). Vri alleles act not only as dominant maternal
      enhancers of embryonic dorsoventral patterning defects caused by easter and
      decapentaplegic (dpp) mutations, but also as dominant zygotic enhancers of dpp
      alleles for phenotypes in wing. The vri gene encodes a new member of the bZIP
      family of transcription factors closely related to gene 9 of Xenopus laevis,
      induced by thyroid hormone during the tadpole tail resorption program, and NF
      IL3A, a human T cell transcription factor that transactivates the interleukin-3
      promoter. NF-IL3A shares 93% similarity and 60% identity with Vri for a stretch
      of 68 amino acids that includes the bZIP domain. Although all the alleles tested
      behave like antimorphs, the dominant enhancement is also seen with a nonsense
      mutation allele that prevents translation of the bZIP domain. Because of the
      strong domainant enhancement of dpp phenotypes by vri alleles in both embryo and
      wing, and also the similarity between the wing vein phenotypes caused by the vri
      and shortvein dpp alleles, we postulate that vri interacts either directly or
      indirectly with certain components of the dpp (a TGF beta homologue) signal
      transduction pathway.

PMID- 9258680
TI  - A Polycomb and GAGA dependent silencer adjoins the Fab-7 boundary in the
      Drosophila bithorax complex.
AB  - The homeotic genes of the Drosophila bithorax complex are controlled by a large
      cis-regulatory region that ensures their segmentally restricted pattern of
      expression. A deletion that removes the Frontabdominal-7 cis-regulatory region
      (Fab-7') dominantly transforms parasegment 11 into parasegment 12. Previous
      studies suggested that removal of a domain boundary element on the proximal side
      of Fab-7' is responsible for this gain-of-function phenotype. In this article we
      demonstrate that the Fab-7' deletion also removes a silencer element, the iab-7
      PRE, which maps to a different DNA segment and plays a different role in
      regulating parasegment-specific expression patterns of the Abd-B gene. The iab-7
      PRE mediates pairing-sensitive silencing of mini-white, and can maintain the
      segmentally restricted expression pattern of a BXD, Ubx/lacZ reporter transgene.
      Both silencing activities depend upon Polycomb Group proteins. Pairing-sensitive
      silencing is relieved by removing the transvection protein Zeste, but is enhanced
      in a novel pairing-independent manner by the zeste' allele. The iab-7 PRE
      silencer is contained within a 0.8-kb fragment that spans a nuclease
      hypersensitive site, and silencing appears to depend on the chromatin remodeling
      protein, the GAGA factor.

PMID- 9258682
TI  - Paternal transmission of X-linked placental dysplasia in mouse interspecific
      hybrids.
AB  - It has previously been shown that abnormal placental development, i.e., hyper-
      and hypoplasia, occurs in crosses and backcrosses between different mouse (Mus)
      species. These defects are caused mainly by abnormal growth of the
      spongiotrophoblast. The precise genetic basis for these placental malformations
      has not been determined. However, a locus that contributes to the abnormal
      development (Ihpd: interspecific hybrid placental dysplasia) has been mapped to
      the X chromosome. The X-chromosomal location of Ihpd and its site of action, that
      is the spongiotrophoblast, mean that normally only the maternally inherited Ihpd
      locus is active even in female fetuses. However, by making use of the X
      chromosomal inversion In(X)IH, we have produced interspecific hybrid Xp0, in
      which the active X chromosome was inherited from Mus macedonicus males. In
      contrast to XX female and XY male conceptuses from this cross, which have
      hypoplastic placentas, the Xp0 female conceptuses have hyperplastic placentas.
      This finding supports the view that it is expression of the M. macedonicus Ihpd
      locus in the spongiotrophoblast that leads to hyperplasia due to an abnormal
      interaction with M. musculus autosomal loci.

PMID- 9258681
TI  - Germ-line effects of a mutator, mu2, in Drosophila melanogaster.
AB  - A mutator, mu2a, in Drosophila melanogaster potentiates terminal deficiencies. In
      the female germ line the gamma mutant frequency induced by irradiation of mature
      oocytes with 5 Gy increases approximately twofold in heterozygotes and 20-fold in
      homozygotes compared with wild type. The recovery of terminal deficiencies is not
      limited to breaks close to chromosome ends; high frequencies of deficiencies can
      be recovered with breakpoints located in centric heterochromatin or near the
      middle of a chromosome arm. Lesions induced by gamma-rays are repaired slowly in
      mu2a oocytes, but become "fixed" as terminal deficiencies upon fertilization. A
      few lesions induced in wild-type females also produce terminal deficiencies.
      Mutator males do not exhibit an increase in terminal deletions, regardless of the
      germ cell stage irradiated. In addition, there is no increase in the mutant
      frequency when mature sperm are irradiated and fertilize eggs produced by mu2a
      females. The data are consistent with the hypothesis that lesions induced in
      sperm chromosomes are repaired after fertilization, while lesions induced in
      oocyte chromosomes are shunted instead to a mechanism that stabilizes broken
      chromosome ends. We propose that mu2 affects chromosomal structure during
      oogenesis, thereby modulating DNA repair.

PMID- 9258683
TI  - Genetic studies of the mouse mutations mahogany and mahoganoid.
AB  - The mouse mutations mahogany (mg) and mahoganoid (md) are negative modifiers of
      the Agouti coat color gene, which encodes a paracrine signaling molecule that
      induces a swithc in melanin synthesis from eumelanin to pheomelanin. Animals
      mutant for md or mg synthesize very little or no pheomelanin depending on Agouti
      gene background. The Agouti protein is normally expressed in the skin and acts as
      an antagonist of the melanocyte receptor for alpha-MSH (Mc1r); however, ectopic
      expression of Agouti causes obesity, possibly by antagonizing melanocortin
      receptors expressed in the brain. To investigate where md and mg lie in a genetic
      pathway with regard to Agouti and Mc1r signaling, we determined the effects of
      these mutations in animals that carried either a loss-of-function Mc1r mutation
      (recessive yellow, Mc1re) or a gain-of-function Agouti mutation (lethal yellow,
      Ay). We found that the Mc1re mutation suppressed the effects of md and mg, but
      that md and mg suppressed the effects of Ay on both coat color and obesity.
      Plasma levels of alpha-MSH and of ACTH were unaffected by md or mg. These results
      suggest that md and mg interfere directly with Agouti signaling, possibly at the
      level of protein production or receptor regulation.

PMID- 9258684
TI  - Induction of duplication reversion in human fibroblasts, by wild-type and mutated
      SV40 T antigen, covaries with the ability to induce host DNA synthesis.
AB  - Intrachromosomal homologous recombination, manifest as reversion of a 14-kbp
      duplication in the hypoxanthine phosphoribosyl transferase (HPRT) gene, is
      elevated in human cells either stably transformed or transiently transfected by
      the SV40 (simian virus 40) large T antigen gene. Following introduction of wild
      type SV40, or any of several T-antigen point mutations in a constant SV40
      background, we observed a strong correlation between the stimulation of
      chromosomal recombination and induction of host-cell DNA synthesis. Moreover,
      inhibitors of DNA replication (aphidicolin and hydroxyurea) suppress SV40-induced
      homologous recombination to the extent that they suppress DNA synthesis. Stable
      integration of plasmids encoding T antigen also augments homologous
      recombination, which is suppressed by aphidicolin. We infer that the mechanism by
      which T antigen stimulates homologous recombination in human fibroblasts involves
      DNA replicative synthesis.

PMID- 9258686
TI  - Microsatellite polymorphism in natural populations of the wild plant Arabidopsis
      thaliana.
AB  - Variation in repeat number at 20 microsatellite loci of Arabidopsis thaliana was
      studied in a worldwide sample of 42 ecotypes to investigate the pattern and level
      of polymorphism in repetitive sequences in natural plant populations. There is a
      substantial amount of variation at microsatellite loci despite the selfing nature
      of this plant species. The average gene diversity was 0.794 and the average
      number of alleles per locus was 10.6. The distribution of alleles was centered
      around the mean of repeat number at most loci, but could not be regarded as
      normal. There was a significantly positive correlation between the number of
      repeats and the amount of variation. For most loci, the observed number of
      alleles was between the expected values of the infinite allele and stepwise
      mutation models. The two models were rejected by the sign test. Linkage
      disequilibrium was detected in 12.1% of the pairwise comparisons between loci. In
      phylogenetic tree, there was no association between ecotype and geographic
      origin. This result is consistent with the recent expansion of A. thaliana
      throughout the world.

PMID- 9258685
TI  - Single and coincident intragenic mutations attributable to gene conversion in a
      human cell line.
AB  - Two polymorphic sites are located within the heterozygous TK1 locus in the human
      lymphoblastoid cell line TK6: an inactivating frameshift in exon 4 of the
      nonfunctional allele and a phenotypically silent frameshift in exon 7 of the
      functional allele. Through the use of these intragenic polymorphisms and
      microsatellite markers that flank TK1, we demonstrate that partial gene
      conversion accounts for 3/75 (0.04) spontaneous and 9/163 (0.06) X-ray-induced
      TK1- mutants, thus comprising a significant component of forward mutations at
      this locus. In all cases, the conversion tract is < 1 cM, rendering double
      exchange a remote alternate explanation for these results. Sequence analysis of
      full length TK1 cDNA provides rigorous exclusion of deletion events as a
      mechanism for generation of these allelotypes. Detailed examination of
      allelotypes in TK1- mutants identified two mechanisms for the generation of
      coincident sequence alterations that sometimes accompanied gene conversions.
      Mutations within the conversion tract were attributed to either error-prone gap
      filling synthesis during recombinational repair or mismatch repair within a
      heteroduplex region following branch migration. These findings suggest that a
      proportion of point mutations may not be targeted to sites of DNA base damage,
      but rather may arise as secondary consequences from the repair of DNA strand
      breaks.

PMID- 9258688
TI  - Effective size and F-statistics of subdivided populations. II. Dioecious species.
AB  - For a dioecious diploid population subdivided into an arbitrary number of
      subpopulations, we have derived recurrence equations for the inbreeding
      coefficient and coancestries between individuals within and among subpopulations
      and formulas for effective size and F-statistics. Stable population size and
      structure, discrete generations, autosomal inheritance, and the island migration
      model are assumed, and arbitrary distributions of the numbers of male and female
      progeny per family, different numbers and variable migration rates of males and
      females are incorporated in our derivation. Some published equations for
      effective size and F-statistics for a subdivided population are shown to be
      incorrect because several incorrect probabilities are used in the derivation. A
      more general equation for effective size is obtained by finding eigenvalue
      solutions to the recurrence equations for inbreeding coefficient and coancestry
      in this article, which reduces to the simple and familiar expressions derived by
      previous authors for the special case of a single unsubdivided population. Our
      general expressions for F-statistics also reduce to the classical results of
      WRIGHT's infinite island model and its extensions. It is shown that population
      structure is important in determining effective size and F-statistics and should
      be recognized and incorporated into programs for genetic conservation and
      evolution.

PMID- 9258687
TI  - Effective size and F-statistics of subdivided populations. I. Monoecious species
      with partial selfing.
AB  - Assuming discrete generations and autosomal inheritance involving genes that do
      not affect viability or reproductive ability, we have derived recurrence
      equations for the inbreeding coefficient and coancestry between individuals
      within and among subpopulations for a subdivided monoecious population with
      arbitrary distributions of male and female gametes per family, variable pollen
      and seed migration rates, and partial selfing. From the equations, formulas for
      effective size and expressions for F-statistics are obtained. For the special
      case of a single unsubdivided population, our equations reduce to the simple
      expressions derived by previous authors. It is shown that population structure
      (subdivision and migration) is important in determining the inbreeding
      coefficient and effective size. Failure to recognize internal structures of
      populations may lead to considerable bias in predicting effective size.
      Inbreeding coefficient, coancestry between individuals within and among
      subpopulations accrue at different and variable rates over initial generations
      before they converge to the same asymptotic rate of increase. For a given
      population, the smaller the pollen and seed migration rates, the more generations
      are required to attain the asymptotic rate and the larger the asymptotic
      effective size. The equations presented herein can be used for the study of
      evolutionary biology and conservation genetics.

PMID- 9258689
TI  - Phylogeographic structure of white oaks throughout the European continent.
AB  - Patterns of chloroplast DNA (cpDNA) variation were studied in eight white oak
      species by sampling 345 populations throughout Europe. The detection of
      polymorphisms by restriction analysis of PCR-amplified cpDNA fragments allowed
      the identification of 23 haplotypes that were phylogenetically ordered. A
      systematic hybridization and introgression between the eight species studied is
      evident. The levels of subdivision for unordered (GST) and ordered (NST) alleles
      are very high and close (0.83 and 0.85). A new statistical approach to the
      quantitative study of phylogeography is presented, which relies on the
      coefficients of differentiation GST and NST and the Mantel's test. Based on
      pairwise comparisons between populations, the significance of the difference
      between both coefficients is evaluated at a global and a local scale. The mapped
      distribution of the haplotypes indicates the probable routes of postglacial
      recolonization followed by oak populations that had persisted in southern
      refugia, especially in the Iberian peninsula, Italy and the Balkans. Most cpDNA
      polymorphisms appear to be anterior to the beginning of the last recolonization.
      A subset of the preexisting haplotypes have merely expanded north, while others
      were left behind in the south.

PMID- 9258690
TI  - Coalescent theory for a partially selfing population.
AB  - A coalescent theory for a sample of DNA sequences from a partially selfing
      diploid population and an algorithm for simulating such samples are developed in
      this article. Approximate formulas are given for the expectation and the variance
      of the number of segregating sites in a sample of k sequences from n individuals.
      Several new estimators of the important parameters theta = 4N mu and the selfing
      rate s, where N and mu are, respectively, the effective population size and the
      mutation rate per sequence per generation, are proposed and their sampling
      properties are studied.

PMID- 9258691
TI  - Structured coalescent processes on different time scales.
AB  - It is demonstrated that the structured coalescent model can readily be extended
      to include phenomena such as partial selfing and background selection through the
      use of an approximation based on separation of time scales. A model that includes
      these phenomena, as well as geographic subdivision and linkage to a polymorphism
      maintained either by local adaptation or by balancing selection, is derived, and
      the expected coalescence time for a pair of genes is calculated. It is found that
      background selection reduces coalescence times within subpopulations and allelic
      classes, leading to a high degree of apparent differentiation. Extremely high
      levels of subpopulation differentiation are also expected for regions of the
      genome surrounding loci important in local adaptation. These regions will be
      wider the stronger the local selection, and the higher the selfing rate.

PMID- 9258692
TI  - The effects of CEO-board relations on hospital performance.
AB  - This article assesses the relationship between CEO-board relations and hospital
      financial performance. A study of 90 acute care California hospitals examined
      changes in the relations between the CEO and governing board over two time
      periods in 1985 and 1989. The results show that CEO-board participation is an
      effective governance mechanism that significantly enhances hospital performance.

PMID- 9258693
TI  - Building better patient care services: a collaborative approach.

PMID- 9258694
TI  - Managed care and the transformation of the medical rehabilitation industry.
AB  - This article reports the findings of a study analyzing the impact of managed care
      on medical rehabilitation providers in three leading markets: San Diego,
      California; Minneapolis/St. Paul, Minnesota; and Worcester, Massachusetts.
      Changes in utilization patterns and the increasing pressure to reduce costs have
      compelled providers to make numerous strategic adjustments.

PMID- 9258695
TI  - Client satisfaction data and quality improvement planning in managed mental
      health care organizations.
AB  - Quality improvement (QI) planning is enhanced when TQM administrators ensure
      appropriate analysis of client satisfaction (CS) survey data. A cost-effective QI
      strategy is to shift "moderately satisfied" into "maximally satisfied" clients.
      Use of a categorical variable derived from CS data and development of a
      predictive model with Chi Square Automatic Interaction Detection (CHAID) produces
      recommendations for quality improvement.

PMID- 9258696
TI  - Corporate political strategy: incorporating the management of public policy
      issues into hospital strategy.
AB  - Hospitals engage in a variety of strategies designed to anticipate, shape, and
      respond to public policy issues. This article describes corporate political
      strategy and argues for its need throughout a public policy issue's life cycle.

PMID- 9258698
TI  - Commentary: not-for-profit status as a vehicle for sector diversity and
      organization.

PMID- 9258697
TI  - Private hospital care for profit? A reappraisal.
AB  - For-profit, investor-owned health care corporations have become much more active
      in hospital markets previously dominated by the private not-for-profit sector. An
      in-depth examination of the many issues underlying this controversy is provided,
      including a review of the role played by charity care and community benefits,
      access to capital, the relationship between profit and the tax status of health
      care organizations, the role of government oversight and regulation, and the
      quality and availability of health care.

PMID- 9258699
TI  - Commentary: whither the not-for-profit community hospitals--observations on the
      Josephson-Schneller dialogue.

PMID- 9258700
TI  - The strategic agenda for community health care organizations.
AB  - This article proposes a vision, strategies, and structure for the organizations
      that will replace community hospitals. The vision must embrace health rather than
      health care, and cost reduction as an explicit, measured goal. Strategies must
      include immediate cost savings, but also longer-term revision of organizations,
      wage structures, prevention, and medical attitudes. Structures must assure local
      stakeholders their voice in health issues.

PMID- 9258701
TI  - Orientational research into dismissed managers in health care.
AB  - The importance of the competence of managers is illustrated by findings of
      provisional research conducted on the failure of managers in health care (15 case
      studies of dismissed managers in hospitals, nursing homes, and convalescent
      homes). The first guarded conclusion that may be drawn from the preliminary study
      is that, as a rule, the dismissal is based on the attitude and competence of the
      manager ("software") and not on business expertise or technical skill
      ("hardware"). It could be said that the manager in health care is judged more on
      the process than the results.

PMID- 9258702
TI  - Occupational and environmental medicine in New York State.
AB  - New York State (NYS) is home to 7.2% of the population and producer of 8.4% of
      the gross domestic product of the United States. The history and the current
      status of occupational and environmental medicine (OEM) research, educational
      resources, clinical practice patterns, and regulatory framework in NYS are
      reviewed. Changes anticipated or already taking place in health care financing,
      clinical practice patterns, occupational safety and health regulations and
      enforcement, and funding for research and medical education at the national
      level, are already having an impact in OEM activities in NYS.

PMID- 9258703
TI  - Exposure to extremely-low-frequency electromagnetic fields and radiofrequency
      radiation: cardiovascular effects in humans.
AB  - Cardiovascular changes in humans exposed to nonionizing radiation [including
      extremely-low-frequency electromagnetic fields (ELF EMFs) and radiofrequency
      radiation (RFR)] are reviewed. Both acute and long-term effects have been
      investigated. In general, if heating does not occur during exposure, current flow
      appears to be necessary for major cardiovascular effects to ensue, such as those
      due to electric shock. Whereas most studies have revealed no acute effect of
      static or time-varying ELF EMFs on the blood pressure, heart rate, or
      electrocardiogram waveform, others have reported subtle effects on the heart
      rate. The possible health consequences of these results are unknown. Regarding
      long-term effects of ELF EMFs, reports from the former Soviet Union in the early
      1960s indicated arrhythmias and tachycardia in high-voltage-switchyard workers.
      Subsequent studies in Western countries, however, did not confirm these findings.
      These studies are limited by uncertainties regarding exposure durations and
      appropriate control groups. Investigations of acute cardiovascular changes in
      humans purposely exposed to RFR have been limited to studies of magnetic
      resonance imaging (which, in addition to RFR, involves static and time-varying
      magnetic fields). It has been concluded that such exposures, as presently
      performed, are not likely to cause adverse cardiovascular effects. Reports of
      hypertension in workers potentially exposed to high levels of RFR during
      accidents are considered to be incidental (due to anxiety and posttraumatic
      stress). Soviet investigators have also indicated that long-term RFR exposure may
      result in hypotension and bradycardia or tachycardia. Other researchers, however,
      have been incapable of replicating these results, and some scientists have
      attributed the effects to chance variations and mishandling of data. In summary,
      studies have not yielded any obvious cardiovascular-related hazards of acute or
      long-term exposures to ELF EMFs or RFR at levels below current exposure
      standards.

PMID- 9258704
TI  - Assessment of hand-arm vibration exposure among traffic police motorcyclists.
AB  - The aims of this study were (1) to evaluate subjective symptoms in the hand-arm
      system of all traffic police motorcyclists of a city located in the central part
      of Japan and (2) to assess their hand-arm vibration exposure associated with
      traffic police motorcycle riding. The study population consisted of 119
      motorcycling traffic policemen and 49 male controls. By means of a questionnaire,
      information on the occupational history and the presence of subjective symptoms
      in the hand-arm system of all subjects was obtained. Vibration was measured on
      the handlebars of the representative motorcycles and on the hands of the riders.
      The 4- and 8-h energy-equivalent frequency-weighted acceleration as well as the
      lifetime vibration dose were calculated for all police motorcyclists. The
      prevalence of finger blanching in the traffic police motorcyclists was 4.2%, but
      none of the controls had this symptom. The rates of finger numbness (19.3%),
      finger stiffness (16.0%), shoulder pain (13.4%), and shoulder stiffness (45.4%)
      were significantly higher among police motorcyclists as compared with controls.
      The root-mean-square (rms) frequency-weighted acceleration on the handlebars of
      police motorcycles was in the range of 2.2-4.9 m/s2 rms. The computed 4- and 8-h
      energy-equivalent frequency-weighted acceleration values were 2.8-4.5 and 2.0-3.2
      m/s2 rms, respectively. A pattern of increasing percentage prevalence with
      increasing cumulative vibration dose was noticed. The subjects with a lifetime
      vibration dose of more than 20.1 m2 h3 s-4 (in scale) showed significantly higher
      prevalence rates for symptoms in the fingers and shoulders as compared with the
      control group. As occupational vibration exposure of traffic police motorcyclists
      might be considered a risk factor for the development of symptoms in the hand-arm
      system of the riders, its evaluation and control is needed for prevention
      methodology evolution.

PMID- 9258705
TI  - Biological monitoring of vehicle mechanics and other workers exposed to low
      concentrations of benzene.
AB  - It has been suggested that the threshold limit value (TLV) for the time-weighted
      average (TWA), of benzene be lowered because of its possible leukemogenic effect
      at low exposure concentrations. This requires the development of new methods of
      biological monitoring. In this cross-sectional study the diagnostic power of
      blood and breath benzene and of urinary phenol, catechol, hydroquinone, S
      phenylmercapturic acid, and muconic acid were compared in a population of 410
      male workers exposed to benzene in garages, in two coke plants, and in a by
      product plant. Benzene exposure was assessed by personal air sampling (charcoal
      tube and passive dosimeter). In all, 95% of the workers were exposed to less than
      0.5 ppm benzene. According to the multiple regression equation, the muconic acid
      and S-phenylmercapturic acid concentrations detected in nonsmokers exposed to 0.5
      ppm benzene were 0.3 mg/g and 6 micrograms/g, respectively (range 0.2-0.6 mg/g
      and 1.2-8.5 micrograms/g, respectively). With muconic acid very few false
      positive test results were found, and this determination remained reliable even
      around a cutoff level of 0.1 ppm benzene. Moreover, the diagnostic power of this
      test proved to be good even when diluted or concentrated urine samples were not
      excluded. S-Phenylmercapturic acid (S-PMA) also performed fairly well. Blood and
      breath benzene as well as urinary phenol (PH) and hydroquinone (HQ) were clearly
      less suitable biomarkers than muconic acid (MA). Catechol (CA) was not associated
      with occupational benzene exposure. According to the results of biological
      monitoring, the skin resorption of benzene from gasoline or other fuels seems
      negligible. Correlation, multiple regression, and likelihood ratios consistently
      showed that MA and S-PMA concentrations were fairly good indicators of benzene
      exposure in the 0.1- to 1-ppm range, even in a population comprising both smokers
      and nonsmokers. PH, HQ, CA, and blood and breath benzene were less suitable, if
      at all, in the same exposure range.

PMID- 9258706
TI  - Ethnic differences in biological monitoring of several organic solvents. II. A
      simulation study with a physiologically based pharmacokinetic model.
AB  - To improve the reliability of biological monitoring and the development of
      biological limit values, ethnic differences in the biological monitoring of
      several organic solvents were studied in Orientals and Caucasians. Six Caucasian
      and six Oriental volunteers were exposed to each organic solvent in an exposure
      chamber for 6 h at rest. The exposure concentrations were 50 ppm for
      perchloroethylene, 50 ppm for styrene, and 100 ppm for m-xylene, respectively.
      Experimental results were compared with simulation results of a physiologically
      based pharmacokinetic (PB-PK) model. Differences between Orientals and Caucasians
      under occupational exposure were also estimated by extrapolation. The simulation
      results obtained for the Caucasian group showed good agreement with the
      experimental results. However, the Oriental group did not show good agreement
      when the same metabolic parameters values applied to Caucasians were used in the
      PB-PK model. By modification of the metabolic parameters it was possible to get a
      good fit between the model and the results of the Oriental group. The simulation
      results obtained for occupational exposure also showed differences in biological
      levels between the two ethnic groups. Implications of these differences between
      experimental and simulation results are discussed in the context of the
      application of biological monitoring and in the development of biological limit
      values.

PMID- 9258707
TI  - Polychlorinated dibenzo-p-dioxin and dibenzofuran levels and patterns in
      polyvinylchloride and chloralkali industry workers.
AB  - The production of chlorine and vinyl chloride (VCM) is associated with the
      formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated
      dibenzofurans (PCDFs). The objective of the present study was to determine
      whether the levels and congener patterns of PCDDs and PCDFs in the blood of
      workers involved in the production of such substances could be related to their
      occupational environment. PCDD and PCDF levels in blood plasma from VCM and
      chloralkali workers and in referents were determined by means of high-resolution
      gas chromatography/high resolution mass spectrometry (HRGC/HRMS) techniques and
      the results were evaluated through principal component analysis (PCA). The
      overall levels of PCDDs and PCDFs were low, but the relative congener
      distribution detected in the workers differed from that found in the referents.
      1,2,3,4,6,7,8-HpCDF, 1,2,3,4,7,8- and 1,2,3,6,7,8-HxCDFs are congeners related to
      work in VCM and chloralkali industries. Exposure to PCDDs and PCDFs in these
      industrial environments changes the congener-distribution pattern in the blood of
      workers as compared with referents. A combination of isomer-specific analysis of
      PCDDs and PCDFs in blood plasma and PCA is suitable for the differentiation
      between nonoccupational and occupational exposure and provides a means of
      assessing workers' exposure situation in different occupational settings.

PMID- 9258708
TI  - Environmental exposure to gasoline and leukemia in children and young adults--an
      ecology study.
AB  - Benzene is an established cause of leukemia in adults, especially acute non
      lymphocytic leukemia (ANLL). A few studies have indicated that exposure to
      gasoline is a cause of childhood leukemia. The purpose of this study was to
      investigate if environmental exposure to benzene from gasoline and car exhaust
      was associated with leukemia in children and young adults. The exposure to
      gasoline and car exhaust was estimated by the number of cars per area. In this
      ecology study, data on the incidence of cancer in each municipality of Sweden
      during an 11-year period (1975-1985) were compared with the number of cars per
      area. Data on the incidence of cancer for persons aged 0-24 years at diagnosis
      were collected from the National Swedish Cancer Register. The following diagnoses
      were studied: non-Hodgkin's lymphoma, acute lymphocytic leukemia (ALL), chronic
      myeloid leukemia (CML), and acute myeloid leukemia (AML). We found an association
      between AML and car density. In municipalities with more than 20 cars/km2 the
      incidence of AML was 5.5 [95% confidence interval (CI) 4.4-6.8, n = 89] as
      compared with 3.4 (95% CI 1.9-5.7, n = 15) cases per 1 million person-years in
      municipalities with less than 5 cars/km2 (P = 0.05). No association was found for
      the other sites of cancer studied. The association between AML in young adults
      and car density might be attributable to exposure to benzene from gasoline vapors
      and exhaust gases, but further investigations are necessary before any definite
      conclusion can be drawn.

PMID- 9258709
TI  - Effects of exposure to carbon disulfide (CS2) on electrocardiographic features of
      ischemic heart disease among viscose rayon factory workers.
AB  - The objective of the study was to evaluate viscose plant workers for
      electrocardiographic manifestations resulting from exposure to carbon disulfide
      (CS2). A total of 162 workers (118 in an exposure group and 44 in a reference
      group) were evaluated using a health questionnaire, physical check-up,
      biochemical analysis of blood samples and electrocardiograms (ECG). The exposure
      group consisted of workers in the following areas: viscose manufacturing,
      cellophane processing, ripening, and filament spinning. Reference group workers
      were from the administrative office, rolling area, pulp processing, and testing
      office. Only slight differences were found in the biochemical analyses of the two
      groups, with the exception of sodium (Na) levels. Personal and area sampling
      results were found to have a high variation due to different locations within the
      plant and a wide range of manufacturing processes. Highest CS2 concentrations
      were found in the ripening area (54.60 ppm) and the filament spinning area (19.60
      ppm). Using a multiple logistic regression model to control variables (age,
      gender, body mass index, duration of employment, cholesterol, smoking, and
      alcohol), we found a relative risk for ECG abnormalities 4.18 times significantly
      higher for the exposure group. The authors feel that the installation of an
      adequate ventilation system could greatly reduce the risk of workers developing
      CS2-induced cardiovascular abnormalities.

PMID- 9258710
TI  - "Epidemiological practices in assessing small effects": conclusions from a
      conference held in Berlin/Potsdam, Germany, 10-13 October 1995.

PMID- 9258712
TI  - Changes in electrical activity of masseter and temporal muscles after
      temporomandibular joint surgery. A one-year follow up.
AB  - The functioning of the masseter and anterior temporal muscles was recorded by
      electromyography (EMG) in 15 patients with disc interference of the
      temporomandibular joints, before surgery and three months, six months and one
      year afterwards. EMG recordings were made during maximal bite in intercuspal
      position and while chewing. The mean electrical activity in the masseter and
      anterior temporal muscles, both on the operated and nonoperated sides, decreased
      markedly three months after surgery, especially during maximal bite in
      intercuspal position, but increased to above the preoperative values at the one
      year recording in both functions. Statistically, significantly lower activities
      were seen on the operated side in patients with anterior dislocation of the disc
      without reduction, as compared to patients with reduction of the disc. The EMG
      activities of the masseter muscles on the nonoperated side were significantly
      lower in women and in older patients, as well as in patients with a longer
      duration of symptoms than in men and younger patients.

PMID- 9258711
TI  - Reconstruction of the mandible by prefabricated autogenous bone grafts. An
      experimental study in minipigs.
AB  - The aim of the present experimental study was to evaluate the use of
      prefabricated bone grafts for reconstruction of the mandible. In 20 adult
      Gottingen minipigs, prefabricated bone grafts 10 x 12 x 40 mm in size were
      cultivated in scaffolds of pyrolized bovine bone under a polylactic membrane on
      the outside of the mandible during a period of five months. The grafts were
      harvested and transferred to bridge 2- and 4-cm lower mandibular border defects
      and discontinuity defects. Five animals served as ungrafted controls and
      evaluation of the grafts was performed three and five months after grafting. At
      both intervals and in both graft-length groups, the grafted bone volume was
      almost completely preserved inside the scaffolds and exhibited a slight (3
      months) to marked (5 months) increase in bone density by appositional bone
      growth. The inserted screws were histologically integrated into the transplanted
      bone and the grafts were linked to the adjacent mandibular bone without
      intervening soft tissue. The grafts, which were transferred to bridge
      discontinuity defects, were likewise well preserved with direct fusion between
      the grafted bone and local bone. It was concluded that bone grafts can be
      prefabricated from underlying mandibular bone and used for the repair of
      mandibular defects of various length and shape.

PMID- 9258713
TI  - Transforming growth factor and tenascin in synovial chondromatosis of the
      temporomandibular joint. Report of a case.
AB  - Synovial chondromatosis (SC) is an uncommon, benign condition of unknown
      etiology. A case of SC of the temporomandibular joint (TMJ) with the
      immunohistochemical findings of transforming growth factor-beta (TGF) and
      tenascin (TN) is reported. The roles of TGF and TN in SC of TMJ are discussed.

PMID- 9258714
TI  - One-stage immediate reconstruction of partial auricular amputation by dog bite.
AB  - A case of one-stage immediate reconstruction of partial auricular amputation
      secondary to dog bite is presented. Primary reconstruction was performed using
      the cartilage of the avulsed portion of the ear nourished by means of a pedicled
      temporofascial flap and split-thickness skin graft. The perioperative
      antimicrobial protocol is also detailed.

PMID- 9258715
TI  - Patient satisfaction with implant-supported mandibular overdentures. A comparison
      of three treatment strategies with ITI-dental implants.
AB  - In a randomized, controlled clinical trial, 110 edentulous patients with atrophic
      mandibles were treated with International Team for Oral Implantology-dental
      implants using three different treatment strategies: a mandibular overdenture
      supported by two implants with ball attachments, two implants with an
      interconnecting bar, or four interconnected implants. The patients' opinions and
      their social functioning were evaluated by means of a questionnaire directly
      before and 16 months after treatment. Before treatment most patients had
      complaints about the retention of their mandibular denture. Sixteen months after
      treatment almost all patients were generally satisfied with their dentures. Since
      no significant difference was found between the three treatment strategies, it
      was concluded that simple implant treatment such as an overdenture retained by
      two ball attachments is sufficient.

PMID- 9258716
TI  - Computed tomographic study of bone availability for facial prosthesis-bearing
      endosteal implants.
AB  - In a computed tomographic study, 56 patients with facial defects were examined to
      assess the availability of bone for extraoral Branemark implants (3 or 4 mm long,
      3.75 mm diameter) to bear facial prostheses. Bone depths were determined in the
      auriculotemporal (2-8 mm), infraorbital (0-10 mm), lateroorbital (8-14 mm),
      supraorbital (1-14 mm) and medioorbital (1-6 mm) areas as well as at the base of
      the nasal skeleton (1-5 mm). The low values for the supraorbital and infraorbital
      areas were determined at the points closest to the frontal- and maxillary
      sinuses, respectively. Implantation in these areas would be permissible only
      under certain conditions. The very thin osseous structures of the nasal region
      also present problems for implants. In the auriculotemporal region, the bone
      width is always sufficient, but at the orbital margin it can vary from 3 to 8 mm.
      The three-year success rates for implant survival were found to be 100% and 85.8%
      respectively for auricular and orbital defects. No serious skin complications
      were seen. Six patients (10.7%) required secondary corrective surgery in a total
      of 13 implant areas.

PMID- 9258717
TI  - Internal fixation of severely displaced mandibular condylar neck fracture with
      the aid of ramus osteotomy. A revised technique.
AB  - A technique is described whereby the mandibular condyle can be located, replaced
      and fixed in case of a severely displaced fracture with exarticulation of the
      condylar head.

PMID- 9258718
TI  - The pterygoid hamulus as a pain-inducing factor. A report of a case and a
      radiographic study.
AB  - A case is reported of a patient suffering from untraceable pain in the palate.
      The hyperplastic pterygoid hamulus appeared to be the cause of his discomfort. A
      computed tomography study on 20 adult patients revealed a wide variation in the
      anatomy of this region, but a fairly consistent pattern in the left-right
      relationship in the same patient.

PMID- 9258719
TI  - Preoperative imaging in a case of molar retention.
AB  - The use of high resolution spiral computed tomography with additional 2-D
      reconstruction is demonstrated for a patient with a deeply impacted first
      mandibular molar. The precise anatomical localization enabled us to remove the
      tooth without damaging the inferior alveolar nerve.

PMID- 9258720
TI  - Down-regulated expression of CD44 variant 6 in oral squamous cell carcinomas and
      its relationship to regional lymph node metastasis.
AB  - The expression of the adhesion molecule CD44 variant 6 (CD44v6) was studied
      immunohistochemically on 38 oral squamous cell carcinomas (SCCs) and 10 biopsies
      of healthy oral mucosa. The relationship between the expression of CD44v6 and
      regional lymph node metastasis was also investigated. The expression of CD44v6
      was apparently down-regulated in oral SCC, but not in normal oral mucosa.
      Carcinomas expressing lower levels of CD44v6 exhibited more frequent regional
      lymph node metastasis. The expression of CD44v6 showed no statistically
      significant relationship to the degree of differentiation, but tended to be down
      regulated in poorly differentiated carcinoma. No significant relation was found
      between the expression of CD44v6 in primary and metastatic lesions.

PMID- 9258721
TI  - Fine needle aspiration of salivary gland tumors.
AB  - The usefulness of fine needle aspiration (FNA) as a preoperative diagnostic
      procedure was studied in 43 patients with salivary gland tumors. Nine of the
      tumors were malignant and 34 benign. The diagnostic sensitivity of FNA was 88.9%
      (8/9), the specificity 94.1% (32/34) and the accuracy 93.0% (40/43). These
      results indicate that FNA is a highly sensitive and specific screening procedure.

PMID- 9258722
TI  - The use of ulnar microvascular free flap as an emergency solution after a
      complication during radial forearm free-flap raising. A case report.
AB  - While raising a standard radial forearm free flap, the ulnar artery was
      inadvertently cut. Therefore, the flap was raised, pedicled on the ulnar artery
      and vein. The case is discussed in the light of alternative solutions. Sommaire.
      Durant le prelevement d'un lambeau radial libre classique, l'artere cubitale a
      ete accidentellement sectionnee. Le lambeau a donc ete preleve, pedicule sur les
      vaisseaux cubitaux. Les solutions alternatives possibles devant cette
      complication et les raisons de notre choix sont discutees.

PMID- 9258723
TI  - Heterotopic salivary gland adenocarcinoma in the cervical region.
AB  - A case of heterotopic salivary gland adenocarcinoma (HSGA) in the right cervical
      region is presented. The carcinoma cells were positive for alpha-amylase,
      carcinoembryonic antigen, epithelial membrane antigen, cytokeratin as well as for
      expression of human salivary alpha-amylase messenger ribonucleic acid. The
      possibility of HSGA should be considered when an adenocarcinoma producing human
      salivary alpha-amylase is diagnosed away from sites where major and minor
      salivary glands normally are found.

PMID- 9258724
TI  - Sebaceous carcinoma of buccal mucosa. Report of a case.
AB  - A case of sebaceous carcinoma arising in the buccal mucosa is described.

PMID- 9258725
TI  - Solitary plasmocytoma of the mandible--a combined approach for treatment and
      reconstruction.
AB  - A 44-year-old man presented with a solitary plasmocytoma in the left mandible.
      After neoadjuvant radiation therapy and chemotherapy, a bone marrow biopsy was
      taken for cryopreservation. In simulation surgery, tumour resection and primary
      reconstruction were planned on an individual stereolithographic 3-D skull model.
      Radical tumour resection and primary reconstruction using a microvascular iliac
      crest bone graft was performed. In case of extensive osteolysis and/or mandibular
      asymmetry due to tumourous bone enlargement, preoperative model planning has
      proved to be a useful tool for primary reconstruction. In the three-year follow
      up, the patient showed no recurrence of disease.

PMID- 9258726
TI  - Median lip fissures and their management.
AB  - Median lip fissures are an uncommon condition and usually give rise to pain and
      episodes of bleeding. We report three cases of median lip fissures which were
      treated by surgical excision.

PMID- 9258727
TI  - Glomus tumor in the upper lip. A case report.
AB  - A glomus tumor arising in the upper lip of a 54-year-old Japanese man is
      presented.

PMID- 9258728
TI  - The epithelialization process in the healing temporalis myofascial flap in oral
      reconstruction.
AB  - The aim of this study was to investigate prospectively the epithelialization
      process in the healing temporalis myofascial flap (TMF). Eight cats underwent
      maxillectomy and immediate reconstruction with TMF. They were killed at the
      determined time and the reconstructed maxillae were processed for examination by
      light microscopy and scanning electron microscopy. Results revealed that
      epithelialization of the healing TMF was initiated by hyperplastic changes
      followed by active migration of epithelial cells deriving from the wound margins.
      The partial maxillectomy wound was completely covered by a smooth oral mucosa at
      postoperative week 24. The mucosa had histological and ultrastructural features
      different from normal palatal mucosa.

PMID- 9258730
TI  - Magnetic resonance pulmonary angiography and direct imaging of embolus for the
      detection of pulmonary emboli.
AB  - RATIONALE AND OBJECTIVES: The authors developed a two-dimensional breathhold
      magnetic resonance (MR) technique for the direct imaging of pulmonary emboli.
      METHODS: In vitro MR imaging was performed to demonstrate the potential
      generation of clot-blood contrast by in vivo pulmonary embolism (PE). A two
      dimensional magnetization prepared gradient-echo (turbo-FLASH) breathhold
      technique was designed to directly image intravascular emboli by the selective
      nulling of the blood signal. A turbo-FLASH pulmonary angiographic breathhold
      sequence was used to provide spatial localization of detected emboli. Thirteen
      patients with suspected PE were studied; 6 patients underwent conventional
      pulmonary angiography (CPA) and the remaining 7 had diagnoses based on findings
      from other studies. RESULTS: In vitro study of blood clot demonstrated an initial
      rise and then fall in T1 sufficient to generate clot-blood contrast after eight
      days of clot formation. All patients with CPA or alternative study evidence of PE
      were diagnosed as positive with direct embolus imaging MR. There were no false
      positive diagnoses. Three additional emboli were detected using the MR technique
      compared with CPA. The MR pulmonary angiographic sequence provided a useful road
      map for localization of intravascular emboli but was less sensitive for PE
      detection than the embolus imaging technique. CONCLUSIONS: The direct imaging of
      PE is feasible using a simple two-dimensional breathhold technique.

PMID- 9258729
TI  - Reintegration of mobilized titanium implants. An experimental study in rabbit
      tibia.
AB  - The possibility of re-establishing a rigid bone-implant fixation, i.e.
      osseointegration, after mechanical loosening of titanium implants, was evaluated
      in the rabbit tibia. Implants were inserted to engage either one (10 mm long, n =
      24) or two (16 mm long, n = 24) cortical layers and were allowed to heal for six
      weeks. A re-entry was then made and 12 test implants in each group subjected to a
      reverse torque procedure until the integration failed. The remaining nonrotated
      24 implants were left as controls. Thereafter all implants were allowed to heal
      for an additional period of six weeks. At the end of the 12 weeks, the degree of
      integration was assessed by measuring the removal torque for six test and six
      control implants in each group of implant lengths. Histomorphometric measurements
      were also performed on ground sections of the remaining test and control
      implants. A statistically significant higher removal torque was observed for the
      monocortical test implants than for the corresponding control implants. No
      differences were seen for the bicortical implants of either kind, however, no
      morphological differences could be revealed either, when comparing monocortical
      and bicortical test and control implants. These results indicate that
      osseointegrated implants that have been mobilized due to a traumatic disruption
      of the bone-implant interface, may reintegrate if allowed to heal for an
      additional period of time.

PMID- 9258731
TI  - Evaluation of metastases and reactive lymph nodes in Doppler sonography using an
      ultrasound contrast enhancer.
AB  - RATIONALE AND OBJECTIVES: The authors conducted a prospective study in D
      galactose signal-enhanced Doppler sonography of lymph nodes to investigate new
      aspects in differentiating malignant from reactive lymph nodes of patients with
      suspected malignancy of the neck. METHODS: Twenty-one patients with suspected
      squamous epithelial cell carcinoma metastases of the neck were examined by
      Doppler sonography before and after administration of an ultrasound signal
      enhancing agent, consisting of D-galactose microbubbles. Qualitative
      sonomorphology, peak flow rates, and pulsatility and resistive indices were
      assessed. RESULTS: Compared with conventional Doppler, enhanced Doppler
      sonography gave detailed additional information about vascularization of
      metastases or reactive lymph nodes. Signal-enhanced Doppler of metastases showed
      a relatively characteristic pattern of vascularity, therefore facilitating
      differential diagnoses and allowing better discrimination from surrounding
      tissue, demonstrated by the infiltration of neighboring vessels in the neck.
      Concerning reactive lymph nodes, vascularization could be stated and measured in
      many cases only after signal enhancement. Evaluating peak velocities and
      pulsatility and resistive indices could not differentiate significantly malignant
      from reactive lymph nodes. CONCLUSIONS: Administration of a D-galactose-based
      signal-enhancer helps to differentiate malignant from reactive lymph nodes of the
      neck. It is superior to conventional Doppler by improving evaluation of the
      vascularity and could be of use for staging procedures.

PMID- 9258732
TI  - Experimental evaluation of the vascular effects and transport of an iodinated
      macromolecular contrast medium.
AB  - RATIONALE AND OBJECTIVES: For assessment of the tissue blood pool and overall
      vascularity, macromolecular contrast media have significant advantages over low
      molecular weight contrast agents. The authors evaluated the vascular effect and
      transport of a new macromolecular contrast media (MMCM), an iodinated dextran
      polymer of 32 kDa. METHODS: The new MMCM was obtained from dextran activated by
      carboxy methylation, followed by linkage with triiodinated aminophtalamid
      conjugates. To detect whether the tracer induces vascular leakage, MMCM (350 mg
      I/kg) was administered intravenously in 10 mice, or applied on the cremaster
      muscle of 26 mice previously injected with carbon particles; after 30 or 45
      minutes, the cremaster was fixed and examined by optical microscopy. For
      investigation of the vascular transport 3, 5, and 15 minutes after MMCM
      administration, various tissue fragments were processed and examined by electron
      microscopy. RESULTS: In all vascular examined, MMCM does not induce plasma
      extravasation and the probe was detected mostly within the vascular lumen. At the
      ultrastructural level, a small fraction of MMCM was found in endothelial
      plasmalemmal vesicles (endosome-like structures) and, in time, transcytosed to
      the subendothelial space. No intercellular junctions were permeated by MMCM.
      CONCLUSIONS: The MMCM induces no vascular leakage and it is retained mainly in
      the plasma. Transport of MMCM is restricted to endothelial vesicles, which may
      explain, in part, its prolonged vascular space retention.

PMID- 9258733
TI  - The value of immediate cytologic evaluation for needle aspiration lung biopsy.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the role of immediate cytologic
      evaluation (ICE) with fine-needle aspiration biopsy (FNAB) for lung lesions at
      highest risk for pneumothorax. METHODS: A prospective randomized study was
      conducted of 80 patients with lung lesions surrounded by aerated parenchyma
      undergoing FNAB with and without ICE (47 and 33 patients, respectively). An
      analysis of needle passes, procedure time, complications, specimen adequacy,
      diagnostic yield, and accuracy of procedure was made. RESULTS: There was an
      increased number of needle passes with ICE (> or = three passes: 23% [11
      biopsies] versus 3% [1 biopsy]; P = 0.01). Fluoroscopic procedures took longer
      with ICE (median time: 15 versus 9 minutes; P = 0.002) with no difference in
      complication rates. Specimen adequacy was similar (74% and 64%) and the procedure
      was diagnostic in 79% (37 biopsies) with ICE and in 70% (33 biopsies) without
      ICE. There were no significant differences in the sensitivity, specificity, or
      accuracy of the biopsy. CONCLUSIONS: Immediate cytologic evaluation improved
      results marginally with increased procedure time and needle passes. Immediate
      cytologic evaluation may be most useful for lesions at lowest risk of
      complications to assure that a second procedure is not required.

PMID- 9258735
TI  - Generation and observation of radio frequency thermal lesion ablation for
      interventional magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: Recently, there has been increased interest in
      interventional magnetic resonance (MR) imaging and minimally invasive cancer
      therapy via radio frequency (RF) thermal ablation. In this work, we examined RF
      thermal lesion generation in phantoms and ex vivo bovine liver and correlated
      them with MR images under a variety of conditions, which begins our assessment of
      the role of MR imaging in this new method for cancer treatment. METHODS: Radio
      frequency lesions were created in gel phantoms and ex vivo bovine liver, using
      stationary (bovine liver) and variable speed (gel) moving electrodes to create
      lesions with shapes mimicking tumors. Ex vivo bovine liver lesions were made with
      the tissue held at room temperature (n = 4) and in a 37 degrees C saline bath (n
      = 3) using a 16-gauge electrode (tip temperature: 70 degrees C, 80 degrees C, and
      90 degrees C; ablation time: 1-13 minutes). Electrical impedance and RF power
      were plotted during ablation. After ablation, RF-induced lesions were imaged with
      a 0.2-tesla (T) MR system using a variety of pulse sequences. RESULTS: Complex
      shaped lesions were created successfully in phantoms. Averaged maximum ex vivo
      lesion volume made at 90 degrees C ablation experiments holding the tissue
      temperature at 37 degrees C and at room temperature were 1.58 +/- 0.35 cm3 and
      1.0 +/- 0.26 cm3 respectively (confidence interval: 90%). The aspect ratios and
      RF power of the lesions decreased as ablations proceeded. Impedance dropped
      during the first 2 minutes of the ablation. Ex vivo lesions appeared as regions
      of low-signal amplitude in T2-weighted MR images. CONCLUSIONS: Phantom ablation
      experience may be useful and applicable in thermotherapy planning. Lesions made
      in ex vivo bovine liver held at 37 degrees C via a saline bath are larger than
      those created at room temperature. Lesions shapes are ablation time dependent
      until thermal equilibrium is reached. Impedance reduction and lesion formation
      are related; 0.2-T MR systems can image RF energy-induced thermal lesions.

PMID- 9258734
TI  - Technetium 99m tetrofosmin parathyroid imaging. Results with double-phase study
      and SPECT in primary and secondary hyperparathyroidism.
AB  - RATIONALE AND OBJECTIVES: The aim of our study was to evaluate the sensitivity,
      specificity, and positive predictive value (PPV) of technetium 99m (99mTc)
      tetrofosmin double-phase scintigraphy and single-photon emission computer
      tomography (SPECT) in preoperative localization of parathyroid adenoma in case of
      primary and secondary hyperparathyroidism (HPT). METHODS: Sixty-eight consecutive
      patients biochemically or sonographically suspected of parathyroid adenoma were
      included in our study. Apart from biochemical analysis of serum calcium,
      phosphate, and intact parathyroid hormone, double-phase scintigraphy was
      performed in each patient 5 and 45 minutes after injection of 370 MBq 99mTc
      tetrofosmin, followed by SPECT imaging. In consciousness of the scintigraphic
      results, ultrasound of the neck was performed as well to exclude false-positive
      results due to thyroid adenomas. RESULTS: Depending on the results of the
      biochemical analysis in combination with the results of the scintigraphic and
      ultrasound examination, the patients were classified retrospectively into three
      groups: group A with primary HPT (n = 35), group B with secondary HPT (n = 13),
      and group C without any biochemical suspicion of primary or secondary HPT (n =
      20). In group A, double-phase study localized 25 of 36 (69.2%) parathyroid
      adenomas (one double adenoma) as against 34 of 36 (94.4%) with SPECT. Nine
      adenomas could be visualized only by SPECT. The reason for nonvisualization on
      planar scans was suspected to be an ectopic location in 2 cases (retrotracheal
      dislocation, retrovascular dislocation), a maximal diameter less than 15 mm (9-13
      mm) in 6 cases, and oxyphilic-cell-poor cellularity in 1 case. Four false
      positive retention (3 thyroid adenomas and 1 papillary thyroid carcinoma) were
      observed. SPECT showed a sensitivity of 94.4%, a specificity of 85%, and a PPV of
      91.9% in biochemically suspected primary HPT. In group B, planar scintigraphy
      demonstrated 12 hyperplastic glands in 5 of 13 patients, and SPECT demonstrated
      20 hyperplastic parathyroid glands in 8 out of 13 patients, which corresponds to
      a sensitivity of 38% and 61.5%, respectively. CONCLUSIONS: Technetium 99m
      tetrofosmin seems to be a promising alternative tracer with similar capabilities
      to 99mTc sestamibi in localization of parathyroid adenoma. SPECT showed clear
      advantages in terms of sensitivity over planar scintigraphy and should be used at
      least in cases with poor or no uptake in double-phase study. In endemic goiter
      areas, ultrasound of the neck should be performed to exclude false positive
      retention in thyroid adenomas. Technetium 99m tetrofosmin, like 99mTc sestamibi,
      is not ideal for localization of hyperplastic glands in secondary
      hyperparathyroidism because of low sensitivity.

PMID- 9258736
TI  - Three-dimensional computerized reconstruction. Illustration of incremental
      articular cartilage thinning.
AB  - RATIONALE AND OBJECTIVES: The authors have addressed the ability of magnetic
      resonance (MR) imaging to resolve incremental thinning of articular cartilage by
      assessment of three-dimensional (3-D) and two-dimensional (2-D) representations.
      METHODS: Using a porcine knee model, sequential cartilage shavings were
      characterized using a 3-D fat suppressed spoiled gradient-echo (SPGR) MR imaging
      protocol that provided good contrast between high-signal articular cartilage and
      lower signal surrounding tissues. Lesion dimensional measurements were made on
      both MR images and 3-D computerized reconstructions. Volumes of cartilage removed
      were approximately 0.06 mL. RESULTS: Incremental articular cartilage thinning
      typically was apparent on 3-D reconstructed images. Three-dimensional articular
      cartilage reconstructions were effective in depicting location and orientation of
      shaved cartilage regions. Average percent error associated with length and with
      measurements based on 2-D MR images was approximately 19% for observer 1 and 33%
      for observer 2 when compared with direct measurements of the shaved cartilage.
      Average percent error of thickness measurements based on 2-D MR was approximately
      21% for observer 1 and 37% for observer 2. Overall average errors associated with
      length, width, and thickness measurements were approximately 25%. CONCLUSIONS:
      Incremental thinning of articular cartilage can be tracked qualitatively and
      quantitatively using 3-D computerized reconstructions and 2-D MR images. Errors
      associated with the quantitative measurements can be attributed to limitations of
      measurement methods and intrinsic limitation of MR resolution.

PMID- 9258737
TI  - Cerebral metabolic alterations in human immunodeficiency virus-related
      encephalopathy detected by proton magnetic resonance spectroscopy. Comparison
      between sequences using short and long echo times.
AB  - RATIONALE AND OBJECTIVES: The aim of this study is to evaluate comparatively the
      metabolic information afforded by proton magnetic resonance (MR) spectroscopy
      with stimulated-echo acquisition mode (STEAM) (echo time [TE], 20 mseconds) and
      point-resolved spectroscopy sequence (PRESS) (TE, 135 mseconds) spectra in HIV
      related encephalopathy. METHODS: Sixty-three human immunodeficiency virus (HIV)
      patients and 8 controls were examined by single-voxel proton MR spectroscopy at
      1.5 tesla, using both PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds)
      sequences performed during the same MR examination, in the same volume of
      interest. Cerebral atrophy was quantitated using bicaudate ratio (BCR) and
      bifrontal ratio (BFR). RESULTS: With the STEAM (TE, 20 mseconds) spectra, mean N
      acetylaspartate (NAA)/choline (Cho) and NAA/creatine and phosphocreatine (Cr-PCr)
      ratios are reduced in acquired immunodeficiency syndrome (AIDS) dementia complex
      (ADC) patients but not in neuroasymptomatics. The proportion of inositol signal
      is increased, that of NAA decreased in ADC patients. NAA/Cho and NAA/ Cr-PCr mean
      values measured with PRESS (TE, 135 mseconds) spectra are significantly reduced
      in ADC and neuroasymptomatic patients. Bifrontal ratio only correlates with
      NAA/Cr-PCr and NAA/Cho measured on the PRESS spectrum. PRESS (TE, 135 mseconds)
      spectra allow a definition of different metabolic patterns in HIV-related
      encephalopathy. At last, no correlation has been found between the NAA raw
      signals measured on the PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds)
      spectra obtained in the same MR examination. CONCLUSIONS: STEAM (TE, 20 mseconds)
      spectra provide more metabolic information-namely an evaluation of glial-neuronal
      status-than PRESS (TE, 135 mseconds) spectra, which afford a metabolic
      classification of the HIV-related encephalopathy. Because both sequences afford a
      similar diagnostic gain, MR spectroscopy examination probably requires spectrum
      acquisition with both sequences.

PMID- 9258739
TI  - [(New antimicrobial agent series L): cefcapene pivoxil].

PMID- 9258738
TI  - Fluoroscopic-guided in vivo gastric mapping for assessment of gastric carcinoma.
AB  - RATIONALE AND OBJECTIVES: The authors seek to determine if a new method of
      combining fluoroscopy and nasogastric biopsy can demonstrate the existence and
      boundary limits of a known gastric carcinoma or its premalignant conditions. The
      study is performed in hopes of avoiding unnecessary surgery or limiting
      resection. METHODS: Two cases are presented to illustrate the technique. The
      first had a known gastric carcinoma; the other had adenomatous change in the
      antrum. After topical anesthesia was applied, a nasogastric tube with a coaxial
      biopsy forceps was inserted. Multiple biopsies were taken in a designed
      geographic pattern and sent to pathology. The patient with known carcinoma
      received a total gastrectomy. The specimen was sectioned in the same regions as
      the biopsies to validate mapping technique. RESULTS: Pathology results for
      sectioned stomach were nearly identical to the biopsies showing the technique can
      accurately map the stomach. No adenomatous change in the antrum or other sections
      of the stomach was observed in the second case. This resulted in the patient
      being spared gastric resection. CONCLUSIONS: Fluoroscopic-guided gastric mapping
      can aid in determining the boundaries of a known carcinoma or premalignant
      conditions. Additional cases and follow-up are necessary.

PMID- 9258740
TI  - [Trends in community-acquired infections and their therapy: focused on the role
      of cefcapene pivoxil. A discussion].

PMID- 9258742
TI  - Criteria for evaluation of clinical efficacy of antimicrobial agents on urinary
      tract infection.

PMID- 9258741
TI  - Bactericidal effect of ecabet sodium on clarithromycin- and metronidazole
      resistant clinical isolates of Helicobacter pylori.
AB  - Ecabet sodium showed a bactericidal effect on Helicobacter pylori NCTC 11637
      which is susceptible to antimicrobial agents (Antimicrob. Agents Chemother, 39:
      1295-1299, 1995). In the present study, we investigated the bactericidal effect
      of ecabet sodium on clarithromycin- and metronidazole-resistant strains of
      clinical isolates of H. pylori under acidic conditions. In a buffer supplemented
      with urea at pH 3.0, ecabet sodium decreased the number of viable cells in both
      isolates. In the morphological study, ecabet sodium changed the isolates from the
      bacilliform to the horseshoe-shaped form and denatured the cytoplasm. Ecabet
      sodium also showed the bactericidal effect on both isolates in buffers at pH 4.0
      and 5.0, and the bactericidal effect was dependent on pH, i.e., the lower the pH,
      the greater the effect. These results suggest that the susceptibility of H.
      pylori to antimicrobial agents does not affect the bactericidal effect of ecabet
      sodium on H. pylori.

PMID- 9258743
TI  - Bisphosphonate effects and the bone remodeling transient.
AB  - Published randomized clinical trial data for alendronate, given at a dose of 10
      mg/day, were fitted by a computer algorithm to the currently accepted model of
      the bone remodeling process. The purpose was to determine how much of the
      reported improvement in lumbar spine bone density could be attributed to the
      inevitable remodeling transient and how much might represent positive bone
      balance. Very good fits to the clinical data were easily obtained, indicating the
      general validity of current syntheses of bone remodeling biology. The best fit
      was provided by simulations produced by combinations of 36-38% suppression of
      remodeling activation and positive remodeling balance ranging from 1.1 to 1.4%
      per year. Whole body bone biomarker changes would have suggested both a slightly
      greater degree of suppression and a higher baseline level of remodeling than
      could be provided by any of the simulations if they were to fit the clinical
      data. Either regional skeletal heterogeneity or lack of a one-to-one quantitative
      relationship between remodeling changes and biomarker changes may explain the
      discrepancies between the two approaches.

PMID- 9258744
TI  - Exploiting and bypassing the bone remodeling cycle to optimize the treatment of
      osteoporosis.

PMID- 9258745
TI  - CD44 antibodies inhibit osteoclast formation.
AB  - Osteoclast differentiation is a complex process requiring multiple factors and
      sequential regulation. We have determined that CD44, a cell surface glycoprotein
      that is known to function as an adhesion receptor, is involved in this process.
      By immunocytochemistry, we show that CD44 is expressed in mouse osteoclasts that
      develop in primary cultures of bone marrow cells treated with 1 alpha, 25
      dihydroxyvitamin D3. Monoclonal antibodies to CD44 inhibit osteoclast formation
      in bone marrow cultures in a dose- and time-dependent manner. In contrast, CD44
      Fab monomer antibodies have no effect on osteoclast development, suggesting that
      the inhibition of differentiation by the whole antibodies is facilitated by cross
      linking of CD44 molecules. Cocultures of spleen cells and ST2 bone marrow stromal
      cells indicate that hematopoietic cells mediate the CD44 antibody inhibitory
      effect. CD44 antibodies do not inhibit osteoclast resorption of calcified matrix,
      indicating that CD44 is not absolutely required for resorption activity. These
      observations demonstrate that CD44 may play a role in osteoclast formation and
      suggest mechanisms by which CD44 antibody effects are mediated.

PMID- 9258746
TI  - Down-regulation of gap junctional intercellular communication between
      osteoblastic MC3T3-E1 cells by basic fibroblast growth factor and a phorbol ester
      (12-O-tetradecanoylphorbol-13-acetate).
AB  - To address the relation between osteoblast growth and cell-to-cell communication,
      we examined the effects of basic fibroblast growth factor (bFGF) and 12-O
      tetradecanoylphorbol-13-acetate (TPA), both potent stimulators of osteoblastic
      proliferation, on gap junctional intercellular communication between osteoblastic
      MC3T3-E1 cells. The level of intercellular communication was estimated by a
      photobleaching method. TPA inhibited the degree of intercellular communication in
      two different time-dependent manners. The early (< 1 h) inhibition by TPA was
      consistent with an increase in the phosphorylation of connexin 43 (Cx43). The
      later inhibition was caused by reduction in the total amount of Cx43 on the
      plasma membrane, due to the decrease in the level of Cx43 transcripts. These
      qualitative and quantitative modulations by TPA were inhibited by a selective
      inhibitor of protein kinase C, GF109203X. bFGF also attenuated the gap junctional
      intercellular communication. However, short exposure (< 5 h) to bFGF did not
      affect the communication. The fact that the growth factor immediately stimulated
      the phosphorylation of Cx43 indicates that the phosphorylation site(s) affected
      by bFGF was not involved in the inhibition of communication. The decrease in the
      intercellular communication level was detected by the longer exposure (> 8 h) to
      bFGF and paralleled the decline in the Cx-mRNA level. This inhibitory effect of
      bFGF was abolished by the addition of a tyrosine kinase inhibitor, herbimycin A.
      Thus, gap junctional intercellular communication between osteoblasts was down
      regulated by osteoblastic mitogens through different mechanisms of the modulation
      of Cx43.

PMID- 9258747
TI  - Cellular hypertrophy and calcification of embryonal carcinoma-derived
      chondrogenic cell line ATDC5 in vitro.
AB  - During the process of endochondral bone formation, proliferating chondrocytes
      give rise to hypertrophic cells, which then deposit a mineralized matrix to form
      calcified cartilage prior to replacement by bone. Previously, we reported that a
      clonal cell line, ATDC5, undergoes efficient chondrogenic differentiation through
      a cellular condensation stage. Here we report that the differentiated ATDC5 cells
      became hypertrophic at the center of cartilage nodules, when the cells ceased to
      grow. Formation of hypertrophic chondrocytes took place in association with type
      X collagen gene expression and a dramatic elevation of alkaline phosphate
      (ALPase) activity. After 5 weeks of culture, mineralization of the culture could
      be discerned as Alizarin red-positive spots, which spread throughout the nodules
      even in the absence of beta-glycerophosphate. Electron microscopy and electron
      probe microanalysis revealed that calcification was first initiated at matrix
      vesicles in the territorial matrix and that it advanced progressively along the
      collagen fibers in a manner similar to that which occurs in vivo. The infrared
      spectrum of the mineralized nodules indicated two absorption doublets around 1030
      cm-1 and 600 cm-1, which are characteristic of apatitic mineral. Calcifying
      cultures of ATDC5 cells retained responsiveness to parathyroid hormone (PTH): PTH
      markedly inhibited elevation of ALPase activity and calcification in the culture
      in a dose-dependent manner. Thus, we demonstrated that ATDC5 cells keep track of
      the multistep differentiation process encompassing the stages from mesenchymal
      condensation to calcification in vitro. ATDC5 cells provide an excellent model to
      study the molecular mechanism underlying regulation of cartilage differentiation
      during endochondral bone formation.

PMID- 9258748
TI  - Integrin expression and function on human osteoblast-like cells.
AB  - The integrin family of cell adhesion molecules are a series of cell surface
      glycoproteins that recognize a range of cell surface and extracellular matrix
      (ECM)-associated ligands. To date, the precise role of individual integrin
      molecules in bone cell-ECM interactions remains unclear. Cell binding assays were
      performed to examine the ability of normal human bone cells (NHBCs) to adhere to
      different ECM proteins in vitro. NHBCs displayed preferential adhesion to
      fibronectin over collagen types I, IV, and vitronectin and showed low affinity
      binding to laminin and collagen type V. No binding was observed to collagen type
      III. The integrin heterodimers alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1,
      alpha 5 beta 1, alpha v beta 3, and alpha v beta 5 were found to be
      constitutively expressed on the cell surface of NHBCs by flow cytometric
      analysis. The integrins alpha 4 beta 1 and alpha 6 beta 1 were not expressed by
      NHBCs. Subsequent binding studies showed that NHBC adhesion to collagen and
      laminin was mediated by multiple integrins where cell attachment was almost
      completely inhibited in the presence of a combination of function-blocking
      monoclonal antibodies (Mabs) to alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1,
      and beta 1. In contrast, the adhesion of NHBCs to fibronectin was only partially
      inhibited (50%) in the presence of blocking Mabs to alpha 3 beta 1, alpha 5 beta
      1, and beta 1. The attachment of NHBCs to collagen, laminin, fibronectin, and
      vitronectin was also found to be unaffected in the presence of a function
      blocking Mab to alpha v beta 3. The results of this study indicate that beta 1
      integrins appear to be the predominant adhesion receptor subfamily utilized by
      human osteoblast-like cells to adhere to collagen and laminin and in part to
      fibronectin.

PMID- 9258749
TI  - Differential effects of nonsteroidal anti-inflammatory drugs on constitutive and
      inducible prostaglandin G/H synthase in cultured bone cells.
AB  - The production of prostaglandins by osteoblasts is an important mechanisms for
      the regulation of bone turnover. Bone cells contain both inducible and
      constitutive prostaglandin G/H synthase (PGHS-2 and PGHS-1) and these are
      differentially regulated. Nonsteroidal anti-inflammatory drugs (NSAIDs), which
      selectively inhibit one of these enzymes, would be useful in assessing their
      relative roles in bone metabolism. By Northern analysis, only PGHS-2 is expressed
      by the immortalized rat osteoblastic cell line, Py1a, while only PGHS-1 is
      expressed by the rat osteosarcoma cell line, ROS 17/2.8. We tested the relative
      inhibitory potency (IC50) of seven different NSAIDs on these two cell lines. A
      recently described selective inhibitor of PGHS-2, NS-398, was approximately 30
      times more potent in inhibiting PGHS-2 than PGHS-1, and diclofenac was
      approximately 10 times more potent. Both had IC50's of approximately 3 nM for
      PGHS-2 in Py1a cells. Indomethacin, flurbiprofen, naproxen, and piroxicam were
      relatively nonselective with IC50's ranging from 30 nM to 1 microM, while 6
      methoxy-2 naphthyl acetic acid, the active metabolite of nabumetone, was
      inhibitory only at concentrations greater than 1 microM. These results indicate
      that the presently available NSAIDs are unlikely to distinguish completely
      between effects mediated by PGHS-2 or PGHS-1. However, the cell systems employed
      could provide a model for the analysis of new compounds with greater selective
      activity.

PMID- 9258750
TI  - Linkage studies of a Missouri kindred with autosomal dominant
      spondyloepimetaphyseal dysplasia (SEMD) indicate genetic heterogeneity.
AB  - A four-generation kindred (14 affected and 10 unaffected members) from Missouri,
      U.S.A. in which spondyloepimetaphyseal dysplasia (SEMD) had been inherited as an
      autosomal dominant disorder was investigated for linkage to 13 candidate loci:
      COL2AI, COL9AI, COL9A2, COL9A3, COL10A1, COL11A1, COL11A2, PSACH, FGFR3, decorin,
      CRTL1, COMP, and PTHRP. Mutations of COL2A1, COL9A2, COL10, and FGFR3 have been
      reported previously in the Strudwick type of SEMD, multiple epiphyseal dysplasia
      type 2 (EDM2), the Schmid type of metaphyseal dysplasia, and in achondroplasia,
      respectively, and the pseudoachondroplasia (PSACH) locus has been mapped to
      chromosome 19p12. In addition, mutations in COL9 and COL11A are associated with
      murine forms of degenerative joint disease and chondroplasia, respectively. The
      family proved informative for 12 of the 13 loci and was uninformative at the
      decorin locus. Linkage between this form of SEMD, designated the Missouri
      variant, SEMDMO, and the 12 informative candidate loci was excluded (LOD scores <
      -2.00 at theta = 0.005 to 0.15), thereby indicating further genetic heterogeneity
      in these inherited disorders of bone and cartilage development.

PMID- 9258751
TI  - Characterization of native and recombinant bone sialoprotein: delineation of the
      mineral-binding and cell adhesion domains and structural analysis of the RGD
      domain.
AB  - Bone sialoprotein is a small, sulfated, and phosphorylated integrin-binding
      glycoprotein apparently found only in tissues that eventually mineralize.
      Nondenatured bone sialoprotein (BSP) purified from rat osteosarcoma cell line
      (UMR 106-01 BSP) culture media is shown to have a hydroxyapatite Kd approximately
      2.6 x 10(-9) M, perhaps the strongest affinity for this mineral of any of the
      matrix proteins. Both native BSP and a 47 kD fragment of UMR-BSP (Fragment 1
      approximately 133A- approximately 265Y) are more potent inhibitors of seeded
      hydroxyapatite crystal growth than recombinant human BSP fragments lacking post
      translational modifications. The recombinant proteins, however, do show
      reproducible inhibitory activity, suggesting that at least some of the strong
      mineral-binding properties are encoded directly within the protein sequence
      itself. BSP facilitates the adhesion of several cell types through its integrin
      binding (RGD) tripeptide sequence. Nuclear magnetic resonance (NMR) analysis of a
      15N-enriched 59 amino acid recombinant domain containing the RGD tripeptide shows
      that the structure of this isolated domain is highly flexible with or without 5
      mM calcium. Previous work has also shown that an endogenous fragment of UMR-BSP
      (Fragment 1) supports cell adhesion in the absence of the RGD sequence. In this
      report, non-RGD cell adhesion sites are localized within conserved amino- and
      carboxy-terminal tyrosine-rich domains of recombinant human BSP. Given the
      proximity of the latter non-RGD cell adhesion site to the RGD tripeptide, a model
      of BSP-receptor interactions is presented.

PMID- 9258752
TI  - Down-regulation of protein kinase C by parathyroid hormone and mezerein
      differentially modulates cAMP production and phosphate transport in opossum
      kidney cells.
AB  - We examined the effects of prolonged exposure to parathyroid hormone (PTH) and
      the protein kinase C (PKC) activator mezerein (MEZ) on cyclic adenosine
      monophosphate (cAMP) production, PKC activity, and Na(+)-dependent phosphate
      (Na/Pi) transport in an opossum kidney cell line (OK/E). A 5 minute exposure to
      PTH stimulated, while a 6 h incubation reduced, cAMP production, Na/Pi transport
      was maximally inhibited under desensitizing conditions and was not affected by
      reintroduction of the hormone. MEZ pretreatment (6 h) enhanced PTH-, cholera
      toxin (CTX)-, and forskolin (FSK)-stimulated cAMP production, suggesting enhanced
      Gs alpha coupling and increased adenylyl cyclase activity. However, PKA- and PKC
      dependent regulation of Na/Pi were blocked in MEZ-treated cells. The PTH-induced
      decrease in cAMP production was associated with a reduction in membrane
      associated PKC activity while MEZ-induced increases in cAMP production were
      accompanied by decreases in membrane and cytosolic PKC activity. Enhanced cAMP
      production was not accompanied by significant changes in PTH/PTH related peptide
      (PTHrP) receptor affinity or number, nor was the loss of Na/Pi transport
      regulation associated with changes in PKA activity. The results indicate that
      down-regulation of PKC by PTH or MEZ differentially modulates cAMP production and
      regulation of Na/Pi transport. The distinct effects of PTH and MEZ on PKC
      activity suggest that agonist-specific activation and/or down-regulation of PKC
      isozyme(s) may be involved in the observed changes in cAMP production and Na/Pi
      transport.

PMID- 9258753
TI  - Cortical remodeling following suppression of endogenous estrogen with analogs of
      gonadotrophin releasing hormone.
AB  - The effects of estrogen suppression on osteonal remodeling in young women was
      investigated using transiliac biopsies (eight paired biopsies + four single pre;
      three single post biopsies) taken before and after treatment for endometriosis (6
      months) with analogs of gonadotrophin releasing hormone (GnRH). Estrogen
      withdrawal increased the proportion of Haversian canals with an eroded surface
      (106%, p = 0.047), a double label (238%, p = 0.004), osteoid (71%, p = 0.002),
      and alkaline phosphatase (ALP) 116%, p = 0.043) but not those showing tartrate
      resistant acid phosphatase (TRAP) activity (p = 0.25) or a single label (p =
      0.30). Estrogen withdrawal increased TRAP activity in individual osteoclasts in
      canals with diameters greater than 50 microns (p = 0.0089) and also the number of
      osteons with diameters over 250 microns (p = 0.049). ALP activity in individual
      osteoblasts was increased but not significantly following treatment (p = 0.051).
      Wall thickness was significantly correlated with osteon diameter (p < 0.001). In
      a separate group of patients (four pairs + one post biopsy) on concurrent
      treatment with tibolone, there was no significant increase in the osteon density,
      cortical porosity, median canal diameter, or the markers of bone formation and
      resorption. Enzyme activities and numbers of active canals were also not
      increased with the concurrent treatment, but there was still an increase in the
      osteon diameter. As previously shown for cancellous bone, estrogen withdrawal
      increased cortical bone turnover. We have now shown that resorption depth within
      Haversian systems was also increased with treatment. The enhanced TRAP activity
      in individual osteoclasts supports the concept that osteoclasts are more active
      following estrogen withdrawal in agreement with theoretical arguments advanced
      previously. Understanding the cellular and biochemical mechanisms responsible for
      increased depth of osteoclast resorption when estrogen is withdrawn may allow the
      development of new strategies for preventing postmenopausal bone loss.

PMID- 9258754
TI  - The effect of vitamin D supplementation on the bone mineral density of the
      femoral neck is associated with vitamin D receptor genotype.
AB  - Recent studies suggest that variations of the vitamin D receptor (VDR) gene are
      related to bone mineral density (BMD). In this study, we examined the effect of
      vitamin D3 supplementation on BMD at the femoral neck in relation to VDR
      genotype. We analyzed 81 women, age 70 years and over, who participated in a
      placebo-controlled clinical trial on the effect of vitamin D3 supplementation
      (400 IU daily for at least 2 years) on BMD and fracture incidence. VDR genotype
      was based on the presence (b) or absence (B) of the BsmI restriction site. Mean
      BMD of the right and left femoral neck was measured at baseline and after 1 and 2
      years. Dietary calcium, body mass index, and years since menopause were assessed
      at baseline while biochemical markers were measured at baseline and after 1 year.
      There was no difference among the BB, Bb, and bb genotype for baseline
      measurements of BMD at the femoral neck (mean and SD, g/cm2: 0.70 (0.10), 0.71
      (0.12), and 0.69 (0.10), respectively), nor for any of the biochemical indices.
      The mean increase of BMD in the vitamin D group relative to the placebo group,
      expressed as percentage of baseline BMD, was significantly higher (p = 0.03) in
      the BB (delta BMD: 4.4%, p = 0.04) and Bb genotype (delta BMD: 4.2%, p = 0.007)
      compared with the bb genotype (delta BMD: -0.3%, p = 0.61). No significant
      changes were found for any of the other measured parameters. The VDR genotype
      dependent effect of vitamin D supplementation in these elderly subjects suggest a
      functional involvement of VDR gene variants in determining BMD.

PMID- 9258755
TI  - Cyclization by a specific lactam increases the ability of human parathyroid
      hormone (hPTH)-(1-31)NH2 to stimulate bone growth in ovariectomized rats.
AB  - Human parathyroid hormone (hPTH)-(1-31)NH2 (Ostabolin), which only stimulates
      adenylyl cyclase (AC) instead of AC and phospholipase-C as do hPTH(1-84) and
      hPTH(1-34), strongly stimulates femoral cortical and trabecular bone growth in
      ovariectomized (OVX) rats. Two side-chain lactams have been introduced in the
      hydrophilic face of the receptor-binding region of the fragment's Ser17-Val31
      amphiphilic alpha-helix in an attempt to develop improved analogs for the
      treatment of osteoporosis. Replacing the polar Lys27 with an apolar Leu on the
      hydrophobic face of this alpha-helix and stabilizing the helix with a lactam
      between Glu22 and Lys26 produced a fragment, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1
      31)NH2, which had six times the AC-stimulating ability of hPTH(1-31)NH2 in ROS
      17/2 rat osteosarcoma cells, but the other helix-stabilizing lactam derivative
      [Leu27]-cyclo(Lys26-Arg30)-hPTH(1-31)NH2 did not have a greater AC-stimulating
      ability than hPTH(1-31)NH2, to stimulate AC in ROS 17/2 rat osteosarcoma cells.
      As expected from AC stimulation being responsible for PTH's anabolic action,
      [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2 was, depending on the experimental
      design, a 1.4 to 2 times better stimulator of trabecular bone growth in the OVX
      rat model than either hPTH(1-31)NH2 or [Leu27]-cyclo(Lys26-Arg30)-hPTH(1-31)NH2.
      Thus, there is now a more potently anabolic derivative of hPTH(1-31)NH2, [Leu27]
      cyclo(Glu22-Lys26)-hPTH(1-31)NH2, which might ultimately prove to be one of the
      more effective therapeutics for osteoporosis.

PMID- 9258756
TI  - Effects of exercise involving predominantly either joint-reaction or ground
      reaction forces on bone mineral density in older women.
AB  - This study compared the effects of two exercise training programs, 11 months in
      duration, on bone mineral density (BMD) in older, sedentary women. Thirty-nine
      women, aged 60-74 years, were assigned to the following groups: (a) a group that
      performed exercises that introduced stress to the skeleton through ground
      reaction forces (GRF) (i.e., walking, jogging, stairs); (b) a group that
      performed exercises that introduced stress to the skeleton through joint-reaction
      forces (JRF) (i.e., weight lifting, rowing); or (c) a no-exercise control group.
      BMD of the whole body, lumbar spine, proximal femur, and distal forearm was
      assessed five times at approximately 3-month intervals. The GRF and JRF exercise
      programs resulted in significant and similar increases in BMD of the whole body
      (2.0 +/- 0.8% and 1.6 +/- 0.4%, respectively), lumbar spine (1.8 +/- 0.7% and 1.5
      +/- 0.5%, respectively), and Ward's triangle region of the proximal femur (6.1 +/
      1.5% and 5.1 +/- 2.1%, respectively). There was a significant in BMD of the
      femoral neck only in response to the GRF exercise program (GRF, 3.5 +/- 0.8%;
      JRF, -0.2 +/- 0.7%). There were no significant changes in BMD in control
      subjects. Among all exercisers, there was a significant inverse (r = -0.52, p <
      0.01) relationship between increases in whole body BMD and reductions in fat
      mass, suggesting a dose response effect of exercise on bone mass. Although
      femoral neck BMD was responsive only to the GRF exercise program, some
      adaptations (i.e., increase in lean body mass and strength) that were specific to
      the JRF exercise program may be important in preventing osteoporotic fractures by
      reducing the risk for falls. It remains to be determined whether all of these
      benefits can be gained through a training program that combines the different
      types of exercises employed in this study.

PMID- 9258757
TI  - Determinants of peak bone mass in Chinese women aged 21-40 years. III. Physical
      activity and bone mineral density.
AB  - Previous studies on the relation between moderate physical activity and bone mass
      have observed conflicting results. Many of these studies have not dissociated the
      role of physical activity by age groups and in relation to the period of peak
      bone mass formation. Our cross-sectional analysis of the baseline data of a
      longitudinal study of 273 women aged 21-40 attempted to evaluate the role of
      moderate physical activity on bone mass around the period of peak bone mass
      attainment. The analyses were carried out separately for the two age groups--21
      30 and 31-40--and had also taken into account the effects of age, dietary calcium
      intake, and lean body mass on bone mineral density (BMD). The total metabolic
      equivalent values (MET) of leisure time physical activity was based on the MET
      values for each activity and the reported time spent on each activity in the past
      year. The results indicated that among the younger group of women, high level of
      leisure time physical activity was associated with higher bone mass at both the
      spine and the hip. Additive effects of physical activity and dietary calcium
      intake on the spine and the hip BMD were observed. Together with age and lean
      body mass, physical activity and dietary calcium intake accounted for 19% of the
      variances of bone mineral at the spine and 9-11% at the hip. Among women aged 31
      40, presumably after the peak bone mass formation, lean body mass as well as fat
      mass have independent strong association with BMD. Physical activity was not
      associated with bone mass in this age group.

PMID- 9258758
TI  - Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)
      2, and IGFBP-3 in osteoporotic patients with and without spinal fractures.
AB  - The present study was performed to investigate the role of insulin-like growth
      factor I (IGF-I), IGF-binding protein-2 (IGFBP-2), and IGFBP-3 in age-dependent
      bone loss in postmenopausal Japanese women. One hundred and sixty-five Japanese
      women aged 43-88 years (mean age, 62) were enrolled in the cross-sectional study.
      Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and
      midradius by dual-energy X-ray absorptiometry or single-photon absorptiometry.
      Serum levels of IGF-I, IGFBP-2, and IGFBP-3 were measured by radioimmunoassay.
      BMD at all sites as well as serum levels of IGF-I and IGFBP-3 declined with age,
      while the serum IGFBP-2 level increased with age. Serum IGFBP-3 and -2 levels
      were positively and negatively correlated with the serum IGF-I level,
      respectively. Serum IGF-I and IGFBP-3 levels showed positive correlationship with
      BMD at any site, particularly at the midradius, while the serum IGFBP-2 level
      showed negative correlation with BMD. Multiple regression analyses showed age
      independent positive correlation between the serum IGF-I level and BMD at all
      sites as well as age-independent positive correlation between the serum IGFBP-3
      level and midradius BMD. The relationship between susceptibility to osteoporotic
      spinal fracture and serum IGF-I, IGFBP-3, or -2 levels was examined by decade to
      exclude the influence of aging. Serum levels of IGF-I and IGFBP-3 were
      significantly lower in subjects with spinal fractures than those without
      fractures at any decade. No significant difference of serum IGFBP-2 level was
      observed between subjects with and without fractures. The present findings
      suggest that IGF-I and IGFBP-3 are important to maintaining bone mass
      quantitatively as well as qualitatively, and that the determination of serum IGF
      I and IGFBP-3 levels could be clinically useful to predict the severity of
      osteoporosis, particularly the risk of bone fracture associated with
      osteoporosis.

PMID- 9258759
TI  - Quantitative ultrasound techniques for the assessment of osteoporosis: expert
      agreement on current status. The International Quantitative Ultrasound Consensus
      Group.
AB  - Quantitative ultrasound (QUS) methods have been introduced in recent years for
      the assessment of skeletal status in osteoporosis. The performance of QUS
      techniques has been evaluated in a large number of studies. Reviewing existing
      knowledge, an international expert panel formulated the following consensus
      regarding the current status of this technology. To date, evidence supports the
      use of QUS techniques for the assessment of fracture risk in elderly women. This
      has been best established for water-based calcaneal QUS systems. Future studies
      should include the predictive validity of other QUS systems. Additional clinical
      applications of QUS, specifically the assessment of rates of change for
      monitoring disease progression or response to treatment, require further
      investigation. Its low cost and portability make QUS an attractive technology for
      assessing risk of fractures in larger populations than may be suitable or
      feasible for bone densitometry. Additional investigations that assess innovative
      QUS techniques in well defined research settings are important to determine and
      utilize the full potential of this technology for the benefit of early detection
      and monitoring of osteoporosis.

PMID- 9258760
TI  - Effects of a new positioner on the precision of hip bone mineral density
      measurements.
AB  - In an attempt to reduce patient positioning errors, the authors tested the use of
      a new hip-specific positioning tool, OsteoDyne's Hip Positioner System (HPS). The
      HPS is an "A" frame splint designed to abduct both legs approximately 15 degrees
      to hold them in full extension at the hips and knees and to lock the feet in a
      neutral position. Seventy volunteer women aged 35-82 years were randomly assigned
      in two age-matched groups (mean age 56 years). Each group underwent two
      consecutive femur dual X-ray absorptiometry (DXA) scans with intermediate
      repositioning using the HPS system and two others utilizing the standard hip
      positioner provided with Hologic and Lunar scanners. One technician performed all
      scans using a Hologic QDR 1000-Plus and Lunar DPX-Plus densitometer. One hundred
      and fifty volunteer women aged 50-84 years (mean age, 64 years) were recruited in
      a multicenter study for the assessment of precision. Each subject underwent three
      consecutive femur DXA scans with intermediate repositioning using the HPS system.
      The coefficient of variation (CV) was significantly improved at the femoral neck
      by the use of the HPS with 0.7 versus 1.2 with the Hologic densitometer but only
      moderately altered at other sites. Similar results were found with the Lunar
      densitometer with improvement of precision at the femoral neck, 0.8 versus 1.8
      with a similar trend but no significant difference at the other regions. No
      statistical difference was noted between the femoral neck BMD measured with the
      HPS system and with the standard positioners in either group. The mean precision
      of data obtained on the QDR 1000+ was 0.8% (range 0.1-1.4) for the femoral neck
      BMD, 1.1% (range 0.1-3.0) for the trochanter BMD, 2.3% (range 0.2-5.2) for Ward's
      triangle BMD, and 0.8% (range 0.1-1.9) for the total femur BMD. The mean
      precision of data obtained on the QDR 2000 was 0.7% (range 0.1-2), 1% (range 0.1
      4.9), 2.6% (range 0.3-5.7), and 0.7% (range 0.1-1.8), respectively. In
      conclusion, data obtained with the new OsteoDyne's HPS seem capable of reducing
      patient positioning errors for the hip measurement. Its use is likely to improve
      confidence in hip bone mineral density measurements.

PMID- 9258761
TI  - Mechanical stimulation of tissue repair in the hydraulic bone chamber.
AB  - A hydraulically activated bone chamber model was utilized to investigate cellular
      and microstructural mechanisms of mechanical adaptation during bone repair. Woven
      trabecular bone and fibrotic granulation tissue filled the initially empty
      chambers by 8 weeks postimplantation into canine tibial and femoral metaphyses.
      Without mechanical stimulation, active bone remodeling to lamellar trabecular
      bone and reconstitution of marrow elements were observed between 8 and 24 weeks.
      In subsequent loading studies, the hydraulic mechanism was activated on one
      randomly chosen side of 10 dogs following 8 weeks of undisturbed bone repair. The
      loading treatment applied an intermittent compressive force (18 N, 1.0 Hz, 1800
      cycles/day) for durations of a few days up to 12 weeks. Stereological analysis of
      three-dimensional microcomputed tomography images revealed an increase in
      trabecular plate thickness and connectivity associated with the loaded repair
      tissue microstructure relative to unloaded contralateral controls. These
      microstructural alterations corresponded to an over 600% increase in the apparent
      modulus of the loaded bone tissue. A significant increase in the percentage of
      trabecular surfaces lined by osteoblasts immunopositive for type I procollagen
      after a few days of loading provided further evidence for mechanical stimulation
      of bone matrix synthesis. The local principal tissue strains associated with
      these adaptive changes were estimated to range from approximately -2000 to +3000
      mustrain using digital image-based finite element methods. This study
      demonstrates the sensitivity of bone tissue and cells to a controlled in vivo
      mechanical stimulus and identifies microstructural mechanisms of mechanical
      adaptation during bone repair. The hydraulic bone chamber is introduced as an
      efficient experimental model to study the effects of mechanical and biological
      factors on bone repair and regeneration.

PMID- 9258763
TI  - Long-term aminobisphosphonate treatment of fibrous dysplasia: spectacular
      increase in bone density.

PMID- 9258762
TI  - Precision and discriminatory ability of calcaneal bone assessment technologies.
AB  - To determine if measuring skeletal status at the calcaneus is a potentially
      valuable technique for diagnosing osteoporosis, we examined five calcaneal
      assessment techniques in 53 young normal women and 108 postmenopausal women with
      osteoporosis and compared these measurements to dual-energy X-ray absorptiometry
      (DEXA) at the calcaneus, hip, and spine. The five instruments, including single
      energy X-ray absorptiometry (SEXA) and four quantitative ultrasound (QUS)
      instruments, were evaluated for precision, ability to discriminate osteoporotic
      from young normal subjects, and correlation to the other instruments. The
      coefficient of variation (%CV) for instrument, positioning, interobserver, and
      short-term precision of the five calcaneal instruments ranged from 1.34-7.76%,
      1.63-7.00%, 1.84-9.44%, and 1.99-7.04%, respectively. The %CVs for positioning,
      interobserver, and short-term precision were similar for calcaneal DEXA,
      calcaneal SEXA, and stiffness (as measured by Achilles). The %CVs for instruments
      precision were similar between calcaneal DEXA and SEXA. The ability of the five
      calcaneal instruments to discriminate osteoporotic from young normal subjects was
      similar based on the analysis of area under the receiver operating characteristic
      curves (range 0.88-0.93) and equivalent to DEXA of the calcaneus and hip (0.88
      0.93). The correlations between the measurements of five calcaneal instruments
      were strong (0.80 < or = r < or = 0.91, p < 0.001). These data suggest that
      although the precision is variable, the calcaneal QUS and SEXA instruments can
      discriminate between osteoporotic patients and young normal controls and appear
      to be a useful technique for assessment of osteoporosis.

PMID- 9258764
TI  - Standardization of femur BMD.

PMID- 9258765
TI  - CD4+ CD7- T cells: a separate subpopulation of memory T cells?
AB  - The CD7 molecule is apparently involved in T cell activation but is absent in a
      substantial subpopulation of human T cells under physiological and certain
      pathological conditions. The majority of CD7- T cells expresses TCR alpha/beta
      and is of CD4+ helper and CD45R0+CD45RA- memory phenotype. After birth,
      percentages and absolute numbers of circulating CD7- T cells increase
      significantly during aging. A number of molecules thought to be involved in organ
      specific T cell homing are preferentially expressed within the subset of CD4+CD7-
      T cells. Specific absence of CD7 antigen expression on T cells is observed in a
      variety of pathologic conditions such as cutaneous T cell lymphoma, HIV
      infection, rheumatoid arthritis, and kidney transplantation. Current in vitro
      results suggest that specific downregulation of CD7 antigen expression in T cells
      reflects a separate and stable differentiation state occurring late in the immune
      response. Expansion of CD7- T cells in vivo has been found in certain diseases
      associated with chronically repeated T cell stimulation. The potential
      pathophysiological significance of this T cell subset in certain human diseases
      is discussed.

PMID- 9258766
TI  - Genetic dissection of lupus nephritis in murine models of SLE.

PMID- 9258767
TI  - The serum factor from patients with ulcerative colitis that induces T cell
      proliferation in the mouse thymus is interleukin-7.
AB  - The disturbance of immune regulatory T cells is related to the pathogenesis of
      ulcerative colitis. Here we demonstrated and characterized the serum factor from
      ulcerative colitis patients that induced proliferation of intrathymic T cells.
      The factor isolated from the patient sera by a combination of gel filtration and
      anion-exchange chromatography induced proliferation of CD4+CD8- intrathymic T
      cells in the organ-cultured embryonic mouse thymus. Purification and amino acid
      sequence analysis of the serum factor demonstrated that the N-terminal 12
      sequence was homologous to that of interleukin-7. SDS-PAGE and Western blot
      confirmed that purified serum factor was interleukin-7. Enzyme immunoassay
      demonstrated that the serum interleukin-7 concentration was significantly
      increased in the patients. PCR and Southern blot hybridization demonstrated that
      interleukin-7 mRNA expression was increased in the thymus tissues from patients
      but decreased in the colonic mucosa. Since interleukin-7 is a crucial cytokine
      for proliferation and differentiation of T cells in the thymus, the present study
      indicates that interleukin-7 may contribute to the disturbance of immune
      regulatory T cells in ulcerative colitis.

PMID- 9258768
TI  - Correlation between interferon production and clinical disease activity in
      patients with multiple sclerosis.
AB  - We determined the interferon (IFN) serum levels and in vitro activated IFN
      production in eight patients with relapsing/ remitting multiple sclerosis (MS),
      using a whole-blood test system and the mitogen concanavalin A and the viral
      antigen Newcastle disease virus for induction of the IFN production. During the
      overall study period of 12 months we observed, in relation to clinical disease
      progression, a biphasic increase in the individual IFN alpha and IFN gamma
      production. While mitogen-induced IFN gamma synthesis showed a significant
      augmentation prior to the onset of a new relapse (P < 0.05), virus-induced IFN
      alpha production showed a temporal delayed increase which was related to clinical
      remission (P < 0.01). The observed fluctuations in the individual production of
      both IFN subtypes were not reflected in the sera of the patients. Although the
      reason for the temporal different imbalance in the production of both IFN
      subtypes remains unknown, the observed association between increased IFN alpha
      production and clinical remission emphasizes a possible role for type 1 IFNs in
      the resolution of the MS relapse.

PMID- 9258769
TI  - The growth arresting effect of human immunoglobulin for intravenous use is
      mediated by antibodies recognizing membrane glycolipids.
AB  - Intravenous human IgG (IVIg) given to patients with autoimmune disorders can
      result in significant clinical improvement in some patients. The mechanism(s) by
      which IVIg induces these improvements is(are) not known. We have previously shown
      that IVIg inhibited the proliferation of peripheral blood lymphocytes in
      allogeneic mixed lymphocyte reactions and of autonomously growing human and mouse
      cell lines. In an effort to identify the antigen(s) to which the human IgG binds,
      the human B cell line JY, whose proliferation was inhibited by IVIg, was
      incubated with IVIg, washed extensively with PBS, and lysed. Human IgG from these
      lysates was purified by protein A-Sepharose (IVIgJY). IVIgJY binds to and
      inhibits the proliferation of JY cells and of peripheral blood lymphocytes
      stimulated in a MLR at a 1000- to 10,000-fold lower concentration compared to
      IVIg. IVIgJY was analyzed on a 5-15% gradient SDS/PAGE and only immunoglobulin
      heavy- and light-chain (run under reducing conditions) proteins were detected.
      Immunoprecipitation experiments from JY cell lysates with IVIgJY indicated that
      this IgG did not bind to a protein epitope. Thin-layer immunoblot experiments
      showed that the IVIgJY binds to glycolipids expressed by JY cells and
      lymphocytes. Furthermore, evidence is presented indicating that antiglycolipid
      antibodies are involved in IVIg-induced growth inhibition.

PMID- 9258770
TI  - Specificity and function of "natural" antibodies in immunodeficient subjects:
      clues to B cell lineage and development.
AB  - The origin of natural antibodies has long been a subject of controversy.
      Polyreactive natural antibodies recognize multiple ligands and are thought to
      arise from B1 B cells. Natural antibodies against carbohydrate antigens such as
      Gal alpha 1-3Gal or against blood groups A and B are thought to be "elicited" by
      gut bacteria, but their origin is uncertain. To explore the origin of naturally
      occurring anticarbohydrate antibodies, the specificity and function of the
      xenoreactive antibodies and isohemagglutinins were investigated in
      immunodeficient subjects. Subjects with defects in T cell-dependent antibody
      synthesis had normal levels of xenoreactive natural antibodies, most of which,
      like xenoreactive antibodies from normal individuals, were specific for Gal alpha
      1-3Gal. On the other hand, some subjects with hyper-IgM syndrome who were able to
      synthesize abundant quantities of xenoreactive antibodies and polyreactive
      antibodies were devoid of anti-Gal alpha 1-3Gal antibodies. These results suggest
      that the lineages of B cells giving rise to anti-Gal alpha 1-3Gal antibodies and
      isohemagglutinins are distinct from B1 B cells or at least exist at a more
      "advanced" stage of development than those B1 B cells that give rise to
      polyreactive antibodies. The findings also suggest that B cells which synthesize
      anti-Gal alpha 1-3Gal antibodies and isohemagglutinins may be distinct from B2 B
      cells or exist at a more "primitive" stage of development than B2 B cells that
      synthesize elicited antibodies in normal individuals.

PMID- 9258772
TI  - Primary immunodeficiency syndrome in Spain: first report of the National Registry
      in Children and Adults.
AB  - The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized
      in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID)
      were registered in patients diagnosed between January 1980 and December 1995. PID
      diagnosis was made according to the World Health Organization criteria. The most
      frequent disorders were IgA deficiency (n = 394) and common variable
      immunodeficiency (n = 213), followed by severe combined immunodeficiency (n =
      61), C1 inhibitor deficiency (n = 52), X-linked agammaglobulinemia (n = 49), IgG
      subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A
      comparative study between REDIP and data recently obtained from the European
      registry (ESID Report, 1995) revealed important differences between phagocytic
      disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and
      6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell
      and combined deficiencies concurred with those reported in the European registry,
      69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the
      geographical distribution of cases submitted may indicate underdiagnosis of PID
      in some country areas; surprisingly, the interval between the onset of clinical
      symptoms and diagnosis was significant, even in immunodeficiency diseases, such
      as IgA deficiency, which are easy to diagnose.

PMID- 9258771
TI  - Oligoclonal expansion of CD45RO+ T lymphocytes in Omenn syndrome.
AB  - Omenn syndrome comprises a rare form of combined immunodeficiency with TH2-type
      features of eosinophilia and elevated IgE. Previous studies have led to reports
      of restricted heterogeneity in the T lymphocyte repertoire, and in vitro cloned T
      lymphocytes have been shown to produce IL-4 and IL-5. We hypothesized that (1) T
      cell receptor beta V(D)J DNA sequence analysis would confirm and further define
      the putative restricted heterogeneity, and (2) increased production of IL-4 and
      IL-5 should be found in nonstimulated T lymphocytes, if the molecular
      pathogenesis of Omenn syndrome is an uncontrolled TH2 state. We report the
      results of molecular analyses of T lymphocytes from an untreated 3-month-old
      patient. Oligoclonal T cell receptor beta variable gene usage was found. Sequence
      analysis revealed sets of identical V(D)J sequences, each in-frame, with
      apparently normal N-diversification and no obvious antigen combining site motif.
      From fresh, nonstimulated lymphocytes, proinflammatory TH1 cytokines could be
      detected, but TH2 cytokines could not, so that a simple TH1/TH2 paradigm cannot
      explain the eosinophilia and elevated IgE in Omenn syndrome. Our studies fully
      document for the first time at the molecular level that clonally expanded
      populations of T lymphocytes are present in Omenn syndrome.

PMID- 9258774
TI  - Reluctance of paramedics and emergency medical technicians to perform mouth-to
      mouth resuscitation.
AB  - Recently, a reluctance of lay and medical personnel to perform mouth-to-mouth
      resuscitation (MMR) in hospital and community settings has been documented, with
      45% of respondents declining to perform MMR on a stranger. In the present study,
      we examined whether the perceived risk and fear of contracting infectious
      diseases diminishes the willingness of paramedics and emergency medical
      technicians (EMTs) to perform MMR. Seventy-seven EMTs and 27 paramedics responded
      to a questionnaire, administered by one of two physicians, containing mock
      cardiac arrest scenarios that were designed to assess willingness to perform MMR
      as a citizen responder. Faced with a situation in which an adult stranger
      required MMR, 57% of the participating EMTs and all of the paramedics stated that
      they would refuse to perform MMR. None of the paramedics and only 32.5% of the
      EMTs stated that they would perform MMR on a man in a gay neighborhood. In
      addition, 23% of the EMTs and 37% of the paramedics indicated that they would
      refuse to perform MMR on a child. White respondents were more willing than
      nonwhite respondents to perform MMR. Twenty-nine percent of the prehospital-care
      providers had been in situations requiring MMR in the community, and 40% either
      had walked away or did only external compression. Of those participating
      paramedics and EMTs who had performed MMR in emergency situations, only 45%
      indicated that they would do so again. The respondents indicated that they would
      not be willing to administer MMR because of the fear of contracting infectious
      agents, especially the human immunodeficiency virus. Despite the proven
      effectiveness of MMR in saving lives, paramedics and EMTs are highly reluctant to
      perform MMR as citizen responders. Their perceived risks of contracting
      infectious agents during MMR are high, despite the low actual risks. We recommend
      that instruction in cardiopulmonary resuscitation for providers of pre-hospital
      care, the medical community, and the general public should emphasize the benefits
      of providing MMR, the actual low risks of contracting infectious diseases during
      administration of MMR, and the use of widely available and effective barrier
      masks to minimize any risks due to administration of MMR.

PMID- 9258775
TI  - Abnormal serum biochemistries in association with arterial gas embolism.
AB  - Although diving-associated arterial gas emboli have been thought to embolize the
      cerebral circulation preferentially, more recent evidence suggests that gas
      bubbles disseminate widely and may cause dysfunction in multiple organ systems.
      We performed a retrospective survey of the records of patients presenting with
      diving-associated gas embolism over a 10-yr period to determine the maximal
      levels of serum transaminases and lactate dehydrogenase after a diving accident.
      Twenty-nine subjects with arterial gas embolism were identified whose dive
      profiles suggested that decompression sickness was unlikely. Maximal transaminase
      levels (aspartate amino transaminase = 442 +/- 187 IU/L; alanine amino
      transaminase = 315 +/- 205 IU/L) and lactate dehydrogenase level (800 +/- 227
      IU/L) were significantly greater in the gas embolism patients than those levels
      measured in a group of normal individuals undergoing training dives of similar
      depth and duration. These preliminary studies suggest that arterial gas embolism
      frequently produces significant abnormalities in serum enzyme activity in sport
      divers whose dives would not be expected to produce decompression sickness.
      Arterialized gas bubbles may circulate widely, causing injury outside of the
      cerebral circulation.

PMID- 9258776
TI  - Helium-oxygen therapy in the emergency department.
AB  - Helium is an inert gas with unique physical properties that allow it to be used
      for various respiratory emergencies. Because of its low specific gravity and low
      viscosity, the passage of helium through the respiratory tract is smoother, more
      laminar, and less turbulent than either air or oxygen. These properties have
      prompted the use of helium and oxygen in patients with airway obstructions due to
      tumor, foreign body, edema, or bronchoconstriction. Helium-oxygen has been used
      to facilitate bronchoscopy through small diameter endotracheal tubes and to
      increase the effectiveness of high-frequency jet ventilation. Helium has been
      successful in the treatment of spinal cord decompression sickness seen in divers.
      Helium-oxygen mixtures are commercially available and may be useful in the
      emergency department to treat patients with airway obstruction. This article
      reviews literature concerning the use of helium-oxygen gas mixtures in the
      emergency department. Additional research conducted in the future may further
      define the use of this unique gas mixture in the emergency department.

PMID- 9258777
TI  - A case of Morgagni hernia presenting as pneumonia.
AB  - Morgagni-type diaphragmatic hernias are rare. The overwhelming majority are
      discovered in children who usually present with pneumonia or sepsis. We report an
      unusual case of a 57-yr-old woman with a Morgagni hernia presenting with
      pulmonary symptoms. Complicating the clinical picture, the pneumonia delayed the
      definitive diagnosis until a lateral chest X-ray study revealed loops of bowel in
      the right lower lung fields. It is important to entertain abdominal etiologies in
      the differential diagnosis of a thoracic density.

PMID- 9258773
TI  - Brazilian report on primary immunodeficiencies in children: 166 cases studied
      over a follow-up time of 15 years.
AB  - One hundred sixty-six cases of primary immunodeficiency diseases (PID) (95 males,
      71 females), diagnosed according to WHO criteria, have been registered at the
      Children's Hospital, University of Sao Paulo, Brazil. The following frequencies
      were found: predominantly humoral defects, 60.8% (n = 101); T cell defects, 4.9%
      (n = 8); combined ID, 9.6% (n = 16); phagocyte disorders, 18.7% (n = 31); and
      complement deficiencies, 6% (n = 10). IgA deficiency was the most frequent
      disorder (n = 60), followed by transient hypogammaglobulinemia (n = 14), chronic
      granulomatous disease (n = 14), and X-linked agammaglobulinemia (n = 9). In
      comparison to other (national) reports, we observed higher relative frequencies
      of phagocyte and complement deficiencies. Recurrent infections were the cause of
      death in 12.7%. Allergic symptoms were observed in 41%, mainly in IgA-deficient,
      hypogammaglobulinemic, or hyper-IgE patients, and autoimmune disorders in 5%,
      predominantly in IgA and complement deficiencies. Five patients suffered from BCG
      dissemination; two of them died. This is the first Brazilian report on PID over
      an observation time of 15 years.

PMID- 9258779
TI  - Spinal epidural hematoma progressing to Brown-Sequard syndrome: report of a case.
AB  - A 51-yr-old woman was transferred to the emergency department with nonspecific
      interscapular pain and a progressive right-sided hemiparesis. Physical
      examination and laboratory examination revealed moderate right-sided hemiparesis,
      with no other focal neurologic deficits. A computed axial tomography scan of the
      brain was negative. Emergency arteriography revealed bilateral highgrade
      fibromuscular dysplasia involving the origins of the left and right common
      carotid arteries. The patient was admitted with the presumptive diagnosis of
      embolic cerebrovascular accident. Subsequently, the patient developed a left
      sided sensory deficit, and magnetic resonance imaging of the cervical spine
      revealed a C5-T2 epidural hemorrhage. The patient underwent emergent surgical
      evacuation of the clot and recovered without incident. Spinal epidural hematomas
      are rare and typically present as cord compressions with or without pain rather
      than as unilateral hemiplegia.

PMID- 9258778
TI  - Unusual presentation of cervicothoracic actinomycosis complicated by pericardial
      effusion: a case report.
AB  - Actinomycosis is a chronic-suppurative disease characterized by abscesses and
      draining sinus tracts, with fibrosis and granulation involving the face and neck
      and thoracic or pelvic-abdominal regions. Dermatological findings in patients at
      high risk are the key to the correct diagnosis. Actinomycosis is frequently
      undiagnosed or misdiagnosed until the correct diagnosis is made after surgical
      resection. Alcoholic, homeless, and disadvantaged individuals and patients with
      other factors predisposing to infection including poor dentition, alcoholism,
      seizures, and trauma are common in the emergency department; thus, emergency
      physicians should be aware of the different presentations and complications of
      this disease. The treatment of choice is a high dose of penicillin in conjunction
      with surgical debridement. The prognosis is excellent with correct diagnosis and
      therapy.

PMID- 9258780
TI  - Mediastinal teratoma presenting as massive hemoptysis in an adult.
AB  - Massive hemoptysis is a rare but potentially life-threatening presentation in the
      emergency department (ED). We describe a case of massive hemoptysis caused by a
      mediastinal teratoma in an otherwise healthy young man. The teratoma had invaded
      into a bronchus and was resected successfully. The literature regarding massive
      hemoptysis due to mediastinal teratoma is reviewed. A differential diagnosis for
      massive hemoptysis is presented. The initial management of these patients in the
      ED and the diagnostic options are discussed.

PMID- 9258781
TI  - Massive hemoptysis in a child due to pulmonary arteriovenous malformation.
AB  - Hemoptysis due to pulmonary arteriovenous malformation (PAVM) is rare in
      pediatric patients, but it must be included in the differential diagnosis of
      hemoptysis after other etiologies are excluded. We present a case of an 11-yr-old
      girl who presented with massive hemoptysis due to a PAVM.

PMID- 9258782
TI  - Cocaine-induced wide complex dysrhythmia.
AB  - Cocaine is a local anesthetic with the potential to induce dysrhythmia due to
      direct myocardial sodium channel antagonism similar to class I antidysrhythmic
      drugs. The hallmark of myocardial sodium channel poisoning is wide complex
      dysrhythmia, and the current accepted treatment is intravenous bicarbonate. Wide
      complex dysrhythmio due to cocaine in the absence of myocardial infarction is
      rare, and optimum management is undefined. We report three cases of acute cocaine
      intoxicating during which patients developed wide complex dysrhythmia consistent
      with sodium channel poisoning. In one case, wide complex tachycardia resolved
      without direct treatment. In the other cases, wide complex dysrhythmia resolved
      following intravenous bicarbonate therapy directed at reversing sodium channel
      blockade.

PMID- 9258783
TI  - Current concepts in electrical defibrillation.
AB  - The electrical defibrillator has been proven to be a life-saving device in the
      treatment of cardiac arrest due to ventricular tachycardia or ventricular
      fibrillation. An understanding of the physiology and technology behind this
      device is useful for providers of emergency care. In this article, we review the
      current concepts in electrical defibrillation and briefly discuss the
      developmental history. The physiology and the technical considerations will make
      up the bulk of the discussion. The latest developments in electrical
      defibrillation also will be reviewed.

PMID- 9258784
TI  - Radiologic findings in acute urinary tract obstruction.
AB  - Acute urinary tract obstruction, a common disease in daily practice, often
      requires performance of emergency intravenous urography (IVU). However, the
      spectrum of urographic abnormalities seen with acute obstruction has not been
      thoroughly addressed. The purpose of this study was to explore the IVU findings
      in patients with acute urinary tract obstruction. Records of 380 patients who
      underwent IVU in our hospital during a 6-mo period were reviewed for IVU evidence
      of acute urinary tract obstruction. Of the 380 patients, 53 (14%; 39 men, 14
      women; average age = 43 yr) had acute urinary tract obstruction. All obstructions
      except one were located in the lower one-third of the ureter. The causes of acute
      urinary obstruction included ureteral stones in 34 (64%), ureteral edema or
      lucent stones in 16 (30%), neoplasms in 2 (4%), and inflammatory disease in 1
      (2%). Abnormal radiologic findings were hydroureter in 46, nephropyelographic
      delay in 36, hydronephrosis in 35, interureteric ridge edema in 11, persistent
      dense nephrogram in 6, urine extravasation in 5, vicarious excretion in 1,
      striation in 1, and stricture in 1. Radiographic results were normal in one
      patient. The most common clinical indications of acute ureteral obstruction are
      flank pain and hematuria, and calculi are the major cause. In one-third of
      patients, radiopaque calculi are not detectable with IVU during acute urinary
      tract obstruction. A careful and thorough evaluation of the IVU should be
      performed in patients with clinical indications of acute urinary obstruction.

PMID- 9258785
TI  - Industrial high-voltage electrical burn of the skull, a preventable injury.
AB  - Deep burns of the scalp and skull are often caused by high-voltage electrical
      injuries. Patients with such injuries should be referred to regional burn centers
      that are prepared to excise necrotic burn tissue and cover the devitalized bone
      with a well-vascularized flap. Strategies for prevention of these electrical
      burns are discussed.

PMID- 9258787
TI  - Midazolam: a review of therapeutic uses and toxicity.
AB  - Midazolam is a familiar agent commonly used in the emergency department to
      provide sedation prior to procedures such as laceration repair and reduction of
      dislocations. Midazolam is also effective in the treatment of generalized
      seizures, status epilepticus, and behavioral emergencies, particularly when
      intravenous access is not available. Midazolam is often employed as an induction
      agent for rapid sequence endotracheal intubation. Midazolam has a rapid onset of
      action following intravenous, intramuscular, oral, nasal, and rectal
      administration. Only 50% of an orally administered dose reaches the systemic
      circulation due to extensive first-pass metabolism. Midazolam is metabolized by
      the cytochrome P450 enzyme system to several metabolites including an active
      metabolite, alpha-hydroxymidazolam. Cytochrome P450 inhibitors such as cimetidine
      can profoundly reduce the metabolism of midazolam. Midazolam has a half-life of
      approximately 1 h, but this half-life may be prolonged in patients with renal or
      hepatic dysfunction. Midazolam has been associated with respiratory depression
      and cardiac arrest when used in combination with an opioid, particularly in the
      elderly, although all ages are at risk for respiratory depression. Midazolam is
      relatively free of side effects when used alone and offers several advantages
      over traditional pharmacological agents such as chloral hydrate and the
      combination of meperidine, chlorpromazine, and promethazine. Hiccups, cough,
      nausea, and vomiting are the most commonly reported adverse effects. Many of the
      adverse effects associated with midazolam can be reversed rapidly by the
      administration of flumazenil, a competitive benzodiazepine receptor antagonist.
      Midazolam is a safe and effective agent for providing sedation in the emergency
      department.

PMID- 9258786
TI  - Technical considerations in knot construction. Part I. Continuous percutaneous
      and dermal suture closure.
AB  - The purpose of this investigation was to determine the security of the square
      knot tied with one looped end and one free end versus the security of the square
      knot tied with two free ends. Size 4/0 and size 6/0 monofilament nylon,
      polypropylene, and Biosyn sutures were selected for this evaluation. The
      mechanical performance of these sutures was judged according to knot breakage
      force and number of throws required to attain security. Knots with one looped end
      and one free end require more throws to ensure knot security than do knots
      constructed from two single suture strands of comparable sizes and types of
      sutures.

PMID- 9258788
TI  - Sudden deterioration in an elderly trauma patient.

PMID- 9258789
TI  - Subtle electrical alternans in a large pericardial effusion with tamponade.

PMID- 9258790
TI  - Anonymous demise: mortality in the homeless.

PMID- 9258791
TI  - Emergency medicine administrative managers for the 21st century.

PMID- 9258792
TI  - Neurobiology of timing of symptom onset of common medical emergencies.

PMID- 9258793
TI  - Postexposure rabies prophylaxis.

PMID- 9258794
TI  - Patient noncompliance with rabies immunoprophylaxis.

PMID- 9258796
TI  - Procedural skills in medicine: linking theory to practice.
AB  - Emergency departments offer a unique educational setting where housestaff can be
      exposed to and learn a variety of procedural skills. However, procedural skills
      are often overlooked as an assumed activity without a formal educational context.
      The clinical educator's understanding of the educational principals of teaching
      and learning procedural skills is minimal. This review offers further insight.
      The "psychomotor domain," which represents a hierarchy of learning motor skills,
      and relevant motor learning theory extracted from the educational psychology
      literature are reviewed. These theoretical considerations can be adapted to and
      provide useful information relevant to procedural medicine. Issues of curriculum
      content, methods of teaching and learning, and issues of competence relevant to
      the creation of a procedural skill program are reviewed and discussed.

PMID- 9258795
TI  - Career planning and development for emergency medicine faculty.
AB  - In this article, we propose a methodology to be used by emergency medicine
      faculty members who are interested in career planning and faculty development on
      an individual basis. The basic competencies needed by faculty and methods of
      setting goals are described. Educational courses, workshops, seminars, and self
      study strategies that can be used to provide the basic competencies and meet
      defined goals are described, including the advantages and disadvantages of each
      method, the time commitment, and needed resources. The advantage of this
      methodology is the ability to customize a program to meet individual needs and
      fit into the constraints of available time and monetary resources.

PMID- 9258797
TI  - Medicaid managed care and the emergency department: the first one hundred days.
AB  - Spurred by concerns over increasing costs and variable quality, public and
      private third-party payors are moving their subscribers into managed care plans.
      A central feature of many of these plans is coordination of patient care through
      a primary care provider (PCP). In exchange for easy access to the PCP, patients
      are expected to limit their use of emergency services for episodic, primary, and
      urgent care problems. The State of Connecticut has begun a transition from a fee
      for-service Medicaid plan into a managed care product. Because many Medicaid
      patients had freely used emergency services under the fee-for-service
      arrangement, urban teaching hospital emergency departments rapidly became a focus
      of efforts to control cost and change care-seeking behavior. The Hartford
      Hospital Emergency Department (ED) began screening, education, and referral of
      managed Medicaid patients in the fall of 1995 and recorded experiences with
      patients, administrators, and health care providers involved in the
      implementation of the managed care program. The first 3 mo following plan
      implementation were chaotic and frustrating for all parties, with many
      difficulties due to an unprepared infrastructure. Changes in ED operations and
      maturation of the payor and health care provider network eventually resulted in a
      reasonably smooth system accompanied by reductions in ED visit volumes of at
      least 15%. Continual evolution of role and goals will be necessary if EDs are to
      maintain an active presence in a health care system dominated by managed care
      plans.

PMID- 9258798
TI  - Does reduced length of stay decrease the number of emergency department patients
      who leave without seeing a physician?
AB  - Previous studies have suggested that most emergency department (ED) patients who
      leave without being seen by a physician (LWBS) are nonurgent. Our institution
      developed a fast-track process to reduce length of stay (LOS) for these patients.
      The present study was conducted to determine the effect of reducing LOS on the
      number of ED patients who leave without seeing a physician and the acuity of this
      subset of ED patients. We retrospectively audited, at a tertiary care teaching
      hospital, the number of LWBS patients and their triage status over two 1-mo
      periods. These sampling periods corresponded to immediately before and after
      implementation of five solutions developed by a continuous quality improvement
      (CQI) process to facilitate patient flow through the triage and fast-track areas
      of our ED. Before the CQI process was begun, 2.4% of patients (110/4553) left
      without being seen in a 1-mo study period. Of these, 82 were nonurgent and 28
      were urgent. After implementation of the CQI process, 1.1% of patients (51/4514)
      left without being seen. Of these, 35 were nonurgent and 16 were urgent. There
      was a significant decrease in the LWBS proportion after the CQI process was
      implemented. We conclude that (1) reducing LOS is associated with a decrease in
      the number of ED patients who leave without seeing a physician and (2) many
      patients who leave without being seen are classified as urgent at presentation.

PMID- 9258799
TI  - An Internet primer, Part II: Tools of the Internet.
AB  - This article reviews several of the key tools and protocols that physicians use
      to access information on the internet. They include the World Wide Web,
      electronic mail, newsgroups, Gopher, and file transfer protocol. A general
      description of these tools, and some tips and nuances in their application, are
      discussed. This article is the second in a three-part series, "An Internet
      Primer."

PMID- 9258800
TI  - Hey Bubba, what's the disease du jour?

PMID- 9258801
TI  - The Canadian health care crisis and how to survive it: can cost effectiveness
      save Canadian doctors?

PMID- 9258802
TI  - Developmental patterns of serum 3 alpha-androstanediol glucuronide.
AB  - 3 alpha-androstanediol glucuronide (3 alpha diolG) is a marker of peripheral
      tissue androgen metabolism. There are no previous data regarding complete
      paediatric reference ranges for 3 alpha diolG. In order to obtain reference
      values for 3 alpha diolG we have measured serum levels of 3 alpha diolG in 283
      healthy children and adolescents, 146 boys and 137 girls, age 1 month to 20 years
      and 28 adults. A non-extraction, solid phase radioimmunoassay employing a
      polyclonal antiserum that is specific for 3 alpha diolG was used to measure serum
      3 alpha diolG levels (intra assay variation 5.1-10.1%, inter assay variation 2.7
      9.0%). There was a strong sex and age dependence (r = 0.8; p < 0.0001) of 3 alpha
      diolG levels throughout childhood and adolescence with males showing
      significantly higher levels of the androgen than females (p < 0.05). 3 alpha
      diolG serum levels (nmol/l +/- SD) correlated significantly with pubertal stage
      (p < 0.01). Interestingly, in 35 children with CAH serum 3 alpha diolG levels
      correlated well with clinical and metabolic status, i.e. 17OHP serum levels. In
      summary, we have established percentile curves for 3 alpha diolG levels in
      healthy children and adolescents. We hypothesize that on the basis of our
      reference values the single measurement of serum 3 alpha diolG could serve as a
      means to determine androgen status in children with disorders of puberty and
      sexual development.

PMID- 9258803
TI  - The statistical analysis of neonatal TSH results from congenital hypothyroidism
      screening programs provides a useful tool for the characterization of moderate
      iodine deficiency regions.
AB  - TSH data from the congenital hypothyroidism screening program were analyzed in a
      mild to moderate iodine deficiency region. Neonatal TSH levels were measured at
      day 4-5 of life in 22,384 infants (99% coverage; 51.1% males, 48.9% females). The
      cut off TSH value for recall was established at 20 microUl/ml whole blood. TSH
      values > 20 microUl/ml were excluded from further analysis of the data. The
      frequency distribution analysis showed that the median neonatal TSH level was 2
      microUl/ml and the mode (28% of newborns) corresponded to neonatal TSH values < 1
      microUl/ml. TSH levels above 5 microUl/ml were observed in 14.4% children and the
      97% cut off was 11 microUl/ml. When examined in relation to the areas of newborn
      origin, the individual 97% cut off values varied from 8 to 14 microUl/ml.
      Accordingly, the frequency of TSH levels above the 97% cut off value calculated
      for the entire newborn series (> 11 microUl/ml) ranged from 2.1% to 4.6%. A
      significant correlation was found between the frequency of neonatal TSH levels >
      11 microUl/ml and both goiter prevalence (r2 = 0.88; p = 0.0019) and median
      urinary iodine excretion (r2 = 0.86; p = 0.0077) observed in those areas for
      which epidemiological data were available (n = 7). The results indicate that
      neonatal TSH data from the congenital hypothyroidism screening programs can be
      used for monitoring mild to moderate iodine deficiency regions.

PMID- 9258804
TI  - Hexarelin is a stronger GH-releasing peptide than GHRH in normal cycling women
      but not in anorexia nervosa.
AB  - Anorexia nervosa (AN) is a chronic disease in which an enhanced GH response to
      GHRH, a paradoxic increase after TRH and LHRH, and low IGF1 levels may be present
      according to the patient's clinical state. It is well known that the GH
      hypersecretory state commonly found in the "acute phase" of AN is restored with
      weight gain. The new synthetic hexapeptide, Hexarelin (HEX), which is chemically
      similar to GH-releasing peptide 6, has recently been shown to possess a stronger
      GH-releasing activity than GHRH in humans and to share a synergistic effect with
      GHRH when administered intravenously. Indeed, HEX shows a slight cortisol and PRL
      releasing activity. The aim of the study was to evaluate the effect of i.v.
      administration of old (GHRH) and new (HEX) GH-releasing peptides on GH, PRL and
      cortisol secretion in 9 AN patients in the "recovery phase" of the disease, after
      partial but significant weight gain. For controls we studied 7 normal cycling
      women. No significant difference in GH secretion after GHRH was found between AN
      and controls. GHRH was not able to release cortisol or PRL either in AN or
      controls. HEX produced a significantly (p < 0.05) higher GH peak in controls than
      in AN, while GH AUC was slightly but not significantly higher. Indeed, only in
      controls, HEX was a stronger GH-releasing peptide than GHRH. These findings could
      be explained by the fact that, in AN, GH secretion is already stimulated both by
      reduced IGF1 levels and by increased GHRH/somatostatin ratio. As reported in the
      literature, the action of HEX action is only slightly influenced by variations in
      somatostatin tone. It therefore appears likely that the absolute or relative GHRH
      increase present in AN could partially mimic the unknown hypothalamic factor
      necessary for HEX action on the hypophisis and that, following a structural
      modification of pituitary HEX receptors, GHRH would become able to bind to HEX
      receptors on somatotropic cells. Consequently, the pituitary cells would already
      be over-activated and so unable to respond maximally to HEX stimulation. Indeed,
      in AN, GHRH might play a role of negative modulation in the control of HEX
      action. Finally, in our study HEX was able to produce a persistent PRL release in
      controls but not in AN, thus suggesting that its action could be partially
      dependent on the estrogen milieu, while it stimulated cortisol secretion only
      transiently in the patients studied.

PMID- 9258805
TI  - Cafeteria diet-induced obese rats have an increased somatostatin protein content
      and gene expression in the periventricular nucleus.
AB  - In human obesity, spontaneous and GRF stimulated growth hormone secretion have
      been shown to be blunted. We used cafeteria diet fed obese rats as a model to
      study the central mechanisms involved in growth hormone secretion changes which
      are observed in obesity. We analysed somatostatin messenger RNA and protein
      levels in the hypothalamic periventricular nucleus of the rats by non radioactive
      in situ hybridization and immunocytochemistry respectively. The optical density
      of somatostatin mRNA, measured by a computerized image system, was significantly
      higher in cafeteria diet fed rats (1014 +/- 87 vs 444 +/- 45; p < 0.05). The
      integrated optical density of somatostatin protein was also significantly higher
      in cafeteria rats compared to the control rats (222 +/- 36 vs 114 +/- 24; p <
      0.05). In conclusion, cafeteria diet induced obese rats have a higher
      somatostatin biosynthesis in the periventricular nucleus. Further studies are
      needed to establish the possible link of this increased somatostatin gene
      expression with the decreased GH production.

PMID- 9258807
TI  - Influences of obesity and weight loss on thyroid hormones. A 3-3.5-year follow-up
      study on obese subjects with surgical bilio-pancreatic by-pass.
AB  - The effects of changing body size, energy intake and substrate oxidation on serum
      T4, FT4, T3, FT3 and TSH were investigated in ten morbidly obese subjects (4
      men/6 women; age: 37 +/- 6 years; BMI: 53.8 +/- 6.5 kg/m2; mean +/- SD) who had
      undergone a surgical bilio-pancreatic by-pass in order to reduce their body
      weight. The starting value of serum FT3 was inversely related to the BMI (r = 
      0.63; p < 0.05). After 1-3 months, all the subjects were losing weight and their
      intake of carbohydrates was almost negligible; at this time a significant
      reduction of T3 (-14.6%; p < 0.0001), T4 (-19.5%; p < 0.0001), and FT3 (-10.5%; p
      < 0.001) was observed. Nine to 16 months after surgery, all the subjects were
      still losing weight, although there was no carbohydrate restriction; T3, T4, and
      FT3 were lower than prior to surgery but were beginning to increase. Finally,
      after 36-42 months the body weight of all the patients had been stable for at
      least the previous six months (final BMI: 32.9 +/- 4.1) and their body
      composition, as assessed by bio-impedance, was almost normal; only the
      concentrations of FT3 proved to be significantly lower than the basal value (
      11.2%; p < 0.03). The change in FT3 proved to be independently influenced by the
      degree of fat malabsorption but not by changes in any of the physical
      characteristics considered. All values were always in the normal range; FT4 and
      TSH did not change significantly during the whole period of study. The final
      concentrations of TSH proved to be independently related to the postabsorptive
      protein oxidation (g/24h) (TSH = 2.37-0.018* protein oxidation). These results
      would suggest that nutritional factors have some influence on the blood levels of
      thyroid hormones, especially of FT3, while the removal of obesity does not seem
      to have any independent effect in the long-run.

PMID- 9258806
TI  - Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular
      hyperplasia.
AB  - ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is a rare cause
      of Cushing's syndrome in which adrenal glands become very enlarged, occupied and
      distorted by multiple cortical nodules. We report on such two patients, a 44-year
      old man and a 40-year-old woman. Physical examination revealed in both cases a
      classic cushingoid habit. Laboratory studies showed overt hypercortisolism with
      high urinary free cortisol excretion and elevated serum cortisol with loss of the
      circadian rhythm. Serum cortisol levels were not modified after high dose
      dexamethasone. ACTH levels were undetectable both in baseline conditions and
      following CRH or metyrapone. In both cases, abdominal CT demonstrated bilaterally
      enlarged adrenal glands which were distorted by multiple bumps. 131I
      Norcholesterol scintiscan showed bilateral uptake of the radionuclide. Pituitary
      region was normal at neuroradiologic imaging. Bilateral adrenalectomy was
      performed in both cases. In patient I, adrenal glands weighted 77 and 90 g,
      respectively, while in patient II they were of 90 and 55 g, respectively. At
      histological examination, the adrenal cortex was occupied by multiple nodular
      lesions composed mostly of clear cells. In the internodular regions, no evidence
      of cortical architecture was observed. At the immunohistochemical evaluation,
      both cases displayed KI-67 staining comparable with that of ACTH-dependent
      diffuse hyperplasia. Postoperative course was uneventful and signs of Cushing's
      syndrome resolved in about three months. At the last follow up, the patients are
      going well on glucocorticoid and mineralocorticoid supplementation. Plasma ACTH
      levels are 65 and 107 pg/ml, respectively.

PMID- 9258808
TI  - Pulmonary lymphangioleiomyoma in a patient with multiple endocrine neoplasia type
      I.
AB  - The multiple endocrine neoplasia (M.E.N.) syndromes consist of a group of
      proliferative disorders that selectively target specific sets of endocrine and
      soft tissue cells. Here we report a case of lymphangioleiomyoma of the lung in a
      patient with multiple endocrine neoplasia Type I (M.E.N. I). This is the first
      time such an association has been reported. In our opinion it could possibly be
      ascribed to the genetic predisposition to proliferative disorders of patients
      with M.E.N. syndromes.

PMID- 9258809
TI  - A homozygous nonsense mutation of the human growth hormone receptor gene in a
      Sardinian boy with Laron-type dwarfism.
AB  - Laron-type dwarfism (LTD) is an autosomal recessive disorder due to mutations in
      the GH receptor (GHR) gene. We report the case of a Sardinian boy affected by LTD
      in which we found by direct genomic sequencing a nonsense mutation in the fourth
      exon of the GHR gene (R43X) that determines a premature termination in the
      protein translation process. As the result of the absence of the extracellular
      portion of the GHR this patient had undetectable GH binding protein. This
      molecular defect is identical to that observed in other patients with LTD of
      mediterranean origin.

PMID- 9258810
TI  - Prolactin decrease and shift to a normal-like isoform profile during treatment
      with quinagolide in a patient affected by an invasive prolactinoma.
AB  - Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated
      phosphorylated, deamidated and sulphated forms. The profiles of the forms, as
      determined by isoelectrofocusing (IEF), differ in physiological and pathological
      conditions. The case of a 72-year-old woman affected by an invasive prolactinoma
      is described. The patient had undergone surgical treatment followed by
      radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10
      mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l
      as determined by IRMA, after dilution). We therefore treated the patient with
      quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600
      micrograms/die on day 220. This treatment progressively lowered PRL to 23.2
      micrograms/l. In addition to a decrease in PRL levels, a progressive change in
      the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very
      acidic and during treatment they progressively shifted toward a more basic range.
      For purpose of comparison PRL profiles were also determined in 8 women with
      pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1
      170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels:
      3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17
      52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A
      had a single major peak at isoelectric point (pI) 6.5, while the group B and C
      profiles were more heterogeneous displaying multiple minor peaks, the majority of
      the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for
      group C). During treatment, the profiles of our subject at first resembled those
      of group A; subsequently, when the PRL levels had normalised, the profile
      resembled those noted in group B. Altered (immature?, more glycosilated?, less
      bioactive?) PRL molecules could be secreted by the tumour. These data show that
      quinagolide successfully reduced PRL levels, while inducing secretion of forms
      more similar to those found in women affected by pathological hyperprolactinaemia
      or in normal women.

PMID- 9258811
TI  - Appearance of Graves' disease after percutaneous ethanol injection for the
      treatment of hyperfunctioning thyroid adenoma.
AB  - In this report we describe an unusual patient with hyperfunctioning thyroid
      adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by
      typical Graves' disease. His history revealed the presence of a sister with
      Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the
      nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed
      by the development of severe hyperthyroidism. One month after a second p.e.i.
      cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the
      gland was observed. TSH-receptor and thyroglobulin autoantibodies were
      undetectable before p.e.i. therapy, appeared during the first cycle, and showed a
      further increase after the second p.e.i. therapy cycle. Though spontaneous switch
      to Graves' disease cannot be excluded in patients with toxic nodules, the massive
      release of thyroid materials from follicular cells, among these TSH-receptor
      antigenic components partially denatured by ethanol, may indeed trigger an
      autoimmune response to the TSH-receptor, thus accounting for this observation.
      Patients with possible autoimmune disposition, as selected by familiar history
      and/or laboratory markers should be carefully monitored during p.e.i. treatment.

PMID- 9258812
TI  - Genomic alterations in human glioma cell lines detected by restriction landmark
      genomic scanning.
AB  - Restriction landmark genomic scanning (RLGS) is a 2-dimensional gel analysis
      capable of detecting amplifications, deletions and rearrangements in genomic DNA.
      Using RLGS, we examined genomic DNA from each of 6 human-derived malignant glioma
      cell lines and from normal brain tissue samples. RLGS allows us to screen genomic
      DNAs as approximately 2,000 landmark sites in one procedure without any
      polymorphic markers. The resulting 2,000 spots in tumor samples were compared
      with those in normal brain. Six spots common to 5 of the 6 cell lines showed
      intensified signal, suggesting amplification of a tumor-specific DNA fragment. In
      addition, 25 spots common to 5 of the 6 lines showed a decrease in signal
      intensity, conversely indicating allelic loss of homozygous deletion. These
      results imply the existence of consistent genetic alterations in human glioma.

PMID- 9258813
TI  - Deletion of complex gangliosides of human glioma cells during mitotic cell
      division.
AB  - Glycolipid compositions of the human glioma cell line T98G were studied during
      each phase of the cell cycle to see if those cell surface molecules are concerned
      with cell proliferation. In vitro cultured non-synchronized T98G cells are
      composed of ceramidemonohexoside (CMH), ceramidedihexoside (CDH),
      ceramidetrihexoside (CTH) and neolactotetraosylceramide (nLc4Cer) as neutral
      glycolipids, and of sulfatide (CS), gangliosides GM3, GM2, GD1a and several other
      gangliosides as acidic ones. While total glycolipid content per cellular weight
      was shown to be increased during the M phase, deletion of complex gangliosides
      particularly b-series gangliosides was recognized (p < 0.05). The glycolipid
      profile in other phases was fairly consistent, and there was no glycolipid
      molecule specific to a certain phase of the cell cycle. Relative enhancement of
      simple gangliosides with a decrease of complex ones during mitotic division may
      imply the functional involvement of complex gangliosides in cell-cell or cell
      matrix attachment, which may have to be abandoned during the process of
      detachment from the matrix or cellular cleavage.

PMID- 9258814
TI  - A rat model of leptomeningeal human neoplastic xenografts.
AB  - Leptomeningeal (LM) cancer spread from either a primary brain tumor or a systemic
      cancer is rapidly fatal. Current therapies are ineffective and highly toxic to
      normal nervous system tissues. A xenograft model of LM neoplasia in nude rats
      using a diversity of tumor cell types was established in order to evaluate new
      treatment strategies and to study the pharmacokinetics and biological effects of
      treatments administered into the subarachnoid space. Consistent leptomeningeal
      engraftment and progressive tumor growth was seen after intrathecal injection of
      9 of 13 tumor cells lines, including 2 melanomas, 2 neuroblastomas, 2
      medulloblastomas, 2 gliomas, and 1 breast cancer. Clinical signs ranged from
      steady weight loss commencing from the day after tumor implantation to absence of
      any signs for three weeks until the sudden occurrence of major neurological
      deficits or death. Pathologic examination showed only leptomeningeal tumor growth
      with some cell lines and severe parenchymal invasion with others. CSF cytology
      consistently demonstrated tumor cells in animals with LM disease. Cranial
      magnetic resonance (MR) following intravenous (i.v.) administration of a contrast
      agent revealed enhancing lesions one week following melanoma tumor implantation.
      Reliable ventricular puncture was demonstrated by radiography following
      intraventricular (IVent) injection of an iodinated contrast material. IVent
      instillation of saline, albumin, or antibodies did not provoke clinical toxicity
      or an inflammatory response.

PMID- 9258815
TI  - In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA
      reductase inhibitor, on human glioma cells.
AB  - We analyzed the antiproliferative effect of simvastatin (SV), an inhibitor of 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on human glioma cell
      lines. Inhibition of cell growth with SV was observed in all cell lines tested.
      Different culture conditions altered this inhibition of growth: the lower the
      concentration of fetal bovine serum (FBS) in the medium, the higher the
      inhibitory effect of SV on glioma cells. On morphological examination, we found
      that most of the cells exposed to SV became rounded and the proportion of
      floating cells was increased in a time-dependent manner. Then we examined whether
      exogenously added mevalonic acid reversed the growth inhibitory effect of SV.
      Exogenous mevalonic acid suppressed the inhibitory effect of SV on glioma cells
      in a dose-dependent manner. SV also enhanced the expression of low-density
      lipoprotein (LDL) receptor on glioma cells. We also found that peroxidized LDL (p
      LDL) was cytotoxic to glioma cells and that SV had additive effects on pLDL
      induced cytotoxicity. In a mouse model, growth of glioma cells inoculated into
      nude mice was inhibited by intratumoral injection of both SV and peroxidized LDL.
      These results indicate that mevalonic acid or a metabolite in the cholesterol
      synthesis pathway is necessary for the growth of glioma cells and that
      simvastatin and/or peroxidized LDL should be examined further as potential
      therapeutic agents for gliomas.

PMID- 9258816
TI  - No prediction of recurrence of meningiomas by PCNA and Ki-67
      immunohistochemistry.
AB  - Immunohistochemistry for the expression of the proliferation markers
      proliferating cell nuclear antigen (PCNA) and Ki-67 was studied in 16 non
      recurring meningiomas, 11 meningiomas recurring as benign tumors, 6 recurring as
      atypical meningiomas and in 9 recurring as malignant meningiomas. Non recurring
      meningiomas were defined in this study as tumors without recurrence at least 8
      years after surgery. In addition 16 benign recurrences, 14 atypical- and 12
      malignant meningiomas were studied. In each group great variation of labeling
      indices (LI) = per cent of tumor cells labeled was observed, especially of PCNA
      LIs. The non recurring meningiomas displayed lower mean LI for PCNA and Ki-67
      than did the recurring meningiomas of all groups but the differences were not
      statistically significant. The same pattern was seen when totally resected tumors
      were studied alone. Benign-, atypical-, and malignant meningiomas had labeling
      indices that were related to the grade of malignancy. Only PCNA LIs of atypical-
      and malignant meningiomas were statistically significantly higher than PCNA LIs
      of non recurring meningiomas. The study indicates that PCNA and Ki-67 are of
      minor value as predictors of recurrence of benign meningiomas.

PMID- 9258818
TI  - Effect of neurological dysfunction on health-related quality of life in patients
      with high-grade glioma.
AB  - The purpose of the study was to assess health-related quality of life (HQL) in
      patients with high-grade malignant glioma of the brain. The EORTC core Quality of
      Life Questionnaire (QLQ-C30) and a Brain Cancer Module (BCM20) were administered
      at baseline and several weeks later (follow-up) to 105 patients with either
      recently-diagnosed (n = 41) or recurrent (n = 64) malignant glioma. In addition,
      the attending neurologists completed a standard neurological examination, a
      modified Barthel Activities of Daily Living Index (BADLI) and the Karnofsky
      Performance Scale (KPS). In a preliminary step, the QLQ-C30 was found to have
      acceptable reliability (internal consistency and test-retest reliability). Newly
      diagnosed patients and those with a KPS of 80-100 had significantly better
      physical, role and cognitive functioning and global quality of life with less
      fatigue, visual disorder, motor dysfunction, communication deficit, weakness of
      both legs and trouble controlling the bladder than did those with recurrent
      disease and those with a KPS of 50-70. Similarly, those capable of independent
      activities of daily living, as reported on the BADLI, had higher functioning
      scores and less fatigue than did those who were not independent. Patients with
      dysphasia, mental confusion or motor deficit on neurological examination reported
      significantly lower levels of physical, role, cognitive, emotional and social
      functioning and global quality of life than did patients not having these
      difficulties. They also had significantly more symptoms. In patients with
      deteriorating neurological status between baseline and follow-up, there was a
      marked decline in cognitive, physical, role, emotional and social functioning and
      global quality of life and an increase in fatigue. Thus, there are significant
      differences in HQL between patients with newly-diagnosed and recurrent brain
      cancer and between patients with differing KPS and BADLI scores. In addition, the
      HQL scores provide details not provided by the KPS and the BADLI. Deterioration
      in neurological function is accompanied by significant deterioration in a range
      of HQL domains and in global quality of life.

PMID- 9258817
TI  - Heterogeneity of chemosensitivity in six clonal cell lines derived from a
      spontaneous murine astrocytoma and its relationship to genotypic and phenotypic
      characteristics.
AB  - Heterogeneity in drug sensitivity must, in part, account for the relative lack of
      success with single agent chemotherapy for glioblastoma multiforme (GBM). In
      order to develop in vitro model systems to investigate this, clones derived from
      the VM spontaneous murine astrocytoma have been characterised with regard to drug
      sensitivity. Six clonal cell lines have been tested for sensitivity to a panel of
      cytotoxic drugs using an intermediate duration 35S-methionine uptake assay. These
      lines have previously been extensively characterised with regard to
      morphological, antigenic, kinetic, tumourigenic potential in syngeneic animals
      and chromosomal properties and display considerable heterogeneity. The present
      study indicates that heterogeneity extends to sensitivity to all classes of
      cytotoxic drugs. The greatest difference in sensitivity between the clones was
      seen in response to cell cycle-specific drugs like the Vinca alkaloids (14-fold
      and 20-fold for vincristine (VCR) and vindesine (VIND) respectively), while the
      nitrosoureas, CCNU and BCNU displayed a smaller fold difference in sensitivity
      (4.3 and 3.6-fold difference respectively). All the clones were considerably more
      resistant to the adriamycin (ADM), cis-platinum (C-PLAT) and the Vinca alkaloids
      than the parental cell line although the difference in sensitivity between the
      clones and parental cell line were less marked for the nitrosoureas and
      procarbazine (PCB). It has also been possible to examine the relationship between
      drug sensitivity and the phenotypic and genotypic properties of these clonal cell
      lines. There is a relationship between chromosome number and sensitivity of a
      wide variety of cytotoxic drugs including the nitrosoureas, Vinca alkaloids, PCB,
      C-PLAT, BLEO but not ADR or 5-FU. Clones with small numbers of chromosomes were
      more resistant than clones with gross polyploidy. Similarly, sensitivity to Vinca
      alkaloids and ADM, but not other classes of drugs, was greatest in cells with
      numerous cytoplasmic processes and which did not express large amounts of cell
      surface fibronectin. Preliminary experiments have been conducted on
      reconstituting clonal mixtures of cells with different sensitivity to Vinca
      alkaloids and results from these studies indicate that the drug resistance
      phenotype is dominant, with clonal mixtures of sensitive and resistant cell
      adopting the sensitivity of the more resistant partner. These cell lines should
      prove to be useful models for examining the cell biological basis of drug
      resistance in glioma and may lead to the identification and exploitation of novel
      cellular targets in new therapies for GBM.

PMID- 9258819
TI  - Central neurocytoma: a clinical study of response to chemotherapy.
AB  - We report a case of central neurocytoma treated, after an initial partial
      resection, by chemotherapy, comprising etoposide, ifosfamide and carboplatin. A
      response was obtained and further treatment was given with surgery and
      radiotherapy. There have been no previous reports of response to chemotherapy in
      this relatively rare tumour.

PMID- 9258820
TI  - Problems with delayed and impaired fracture healing remain a challenge to the
      orthopedic trauma surgeon.

PMID- 9258821
TI  - Early histologic and ultrastructural changes in microvessels of periosteal
      callus.
AB  - OBJECTIVE: To document early histological and ultrastructural changes in
      periosteal fracture callus blood vessels. DESIGN: Rabbit control and fractured
      ribs, after healing for three, six, and twelve hours and daily for seven days,
      were evaluated by light and electron microscopy. RESULTS: Control periosteal
      microvessels were formed mainly by endothelial cells and occasionally by
      pericytes. Only these cells displayed basal lamina within the periosteum. Three
      to twelve hours postfracture, periosteal microvessels were little changed. By two
      days postfracture, dramatic increases in size and population of microvessel cells
      resulted in a smaller lumen and thicker wall. Microvessel cells, while retaining
      their basal lamina, had transformed to mesenchymal cells. Transformed pericytes,
      as evidenced by their basal lamina, had extravasated. Three to four days
      postfracture, additional transformed pericytes had extravasated. Within the
      distal periosteal callus, a close spatial relationship among transformed
      microvessels, extravascular mesenchymal cells (some with basal lamina), and
      osteoblasts was present. Four to five days postfracture, within the proximal
      periosteal callus, a close spatial relationship among transformed microvessels
      (rapidly disappearing because of continued extravasation), extravascular
      mesenchymal cells (some with basal lamina), and chondroblasts (some with basal
      lamina) was present. CONCLUSIONS: New evidence showed that after fracture,
      periosteal microvessel endothelial cells and pericytes increased in population
      and transformed to mesenchymal cells. These changes, their subsequent
      extravasation as mesenchymal cells, and their development into chondroblasts were
      verified by basal lamina evidence. New evidence also suggested that continued
      extravasation of transformed microvessel cells rendered the fracture callus
      cartilage avascular.

PMID- 9258822
TI  - Optimal side plate fixation for unstable intertrochanteric hip fractures.
AB  - OBJECTIVES: To quantitatively determine the minimal screw number needed for
      stable side plate fixation to the femoral shaft in treating unstable
      intertrochanteric hip fractures. DESIGN: Laboratory/biomedics study. SETTING:
      Orthopaedic biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: The
      convenience sample was made up of one saw bone, one steel pipe, and ten human
      cadaveric femur specimens. Human specimens were selected by ruling out pathology
      and excess osteopenia. Ten specimens were tested to completion. INTERVENTION:
      Telescoping hip screw and hip screw side plate secured with various numbered
      combinations of side plate screws. MAIN OUTCOME MEASURES: Decreases in tension
      experienced by all previously inserted screws when an additional screw was
      applied were recorded and labeled as "protection." RESULTS: Protection offered by
      a third screw on all previous screws was 787.3 newtons in the steel pipemodel,
      71.2 newtons in the sawbone model, and 158.3 newtons in the human model (p <
      0.005). A fourth bone screw did not decrease tension in previous screws by more
      than 11 newtons. The protective effect of the fourth screw on screw #3 increased
      with decreasing screw application torque by a maximum of 21.8 newtons (p <
      0.005). CONCLUSION: This study suggests that three bone screws provide an optimal
      distribution of tensile forces. The insertional torque used to place screws, once
      screw-plate contact has been established, does not play a significant role in
      screw protection. Additional studies are needed to assess the role of cortical
      bone density, and cyclical loading and bending forces experienced by the side
      plate screws, before definite clinical recommendations can be made.

PMID- 9258824
TI  - Prophylactic vena cava filter insertion in selected high-risk orthopaedic trauma
      patients.
AB  - OBJECTIVES: (a) To determine the incidence and risk factors for the development
      of pulmonary embolism in orthopaedic trauma patients and (b) to determine whether
      prophylactic vena cava filters are efficacious against pulmonary edema in high
      risk patients. DESIGNS: Before and after trial on the incidence of pulmonary
      embolism in the orthopaedic trauma population before and after the introduction
      of prophylactic vena cava filters. SETTING: Tertiary care level I trauma center.
      PATIENTS: Thirty-five patients received prophylactic vena cava filters. These
      patients had a long bone and pelvic, multiple long bone fractures, or a complex
      (Kane's III or IV) pelvic fracture with at least one additional risk-factor at an
      age of > 55 years and an Injury Severity Score of > 16 or requiring prolonged (>
      6 weeks) immobilization. INTERVENTION: Thirty-five patients had vena cava filters
      placed (32 titanium Greenfield filters, Medi-tech/Boston Scientific, Watertown,
      MA; and three Bird's Nest filters, Cook Bloomington, IN). Most filters (n = 33)
      were placed percutaneously in radiology. MAIN OUTCOME MEASURES: (a) Morbidity
      related to filter insertion, (b) incidence of pulmonary embolism in orthopaedic
      trauma population compared with historical controls who did not receive filters,
      and (c) patency of filters. RESULTS AND CONCLUSIONS: Minimal morbidity was
      related to prophylactic vena cava filter insertion. There was a significant (p <
      0.04); (Fisher's exact) decrease in the incidence of pulmonary embolism in the
      orthopaedic trauma population as a whole after the use of prophylactic vena cava
      filters. Follow-up ultrasound showed a 1 and 2-year inferior vena cava patency
      rate of 93.6% +/- 6.2% by life table analysis. We conclude that selected use of
      prophylactic vena cava filters in orthopaedic trauma is safe and decreases the
      incidence of pulmonary embolism.

PMID- 9258825
TI  - Internal fixation in postpartum symphysis pubis rupture: report of three cases.
AB  - We present three patients with postpartum symphysis pubis rupture whose severe
      complaints persisted after conservative treatment. All three ruptures were
      stabilized with open reduction and internal fixation. There were no postoperative
      problems, and implants were removed after a mean period of six months. Patients
      were free of complaints after implant removal. In select cases, operative
      treatment of postpartum symphysiolysis may be indicated.

PMID- 9258823
TI  - Does blood transfusion increase the risk of infection after hip fracture?
AB  - OBJECTIVE: To determine whether allogeneic red blood cell transfusion is a
      predictor for developing an in-hospital postoperative urinary tract, respiratory,
      or wound infection. STUDY DESIGN: Prospective, consecutive. METHODS: Six hundred
      eighty-seven community-dwelling, ambulatory, geriatric hip fracture patients were
      prospectively followed; all patients had operative fracture treatment and
      received perioperative antibiotics. RESULTS: Sixty-eight patients had a culture
      positive infection before operative treatment. One hundred thirty-four of the
      remaining 619 patients (21.6%) developed a postoperative infection, primarily a
      urinary tract infection. The infection rate was 26.8% in transfused patients
      compared with 14.9% in nontransfused patients (p = 0.001). When stratifying by
      the type of infection, only the risk of urinary tract infection was statistically
      significant (p = 0.001). After controlling for the effect of patient age, sex,
      number of preinjury medical comorbidities, American Society of Anesthesiologists
      (ASA) rating of operative risk, fracture type, surgical delay, type of surgery,
      type of anesthesia, operative time, and blood loss, the relationship between
      allogeneic red blood cell transfusion and postoperative urinal tract infection
      remained statistically significant. CONCLUSIONS: Geriatric hip fracture patients
      who receive allogeneic red blood cell transfusions are at higher risk for
      developing a postoperative urinary tract infection than are those patients who
      are not transfused.

PMID- 9258826
TI  - Parturition-induced pelvic dislocation: a report of four cases.
AB  - OBJECTIVE: To describe our experience with four cases of severe pelvic
      dislocation associated with difficult parturition. DESIGN: Retrospective case
      series. PATIENTS: Four patients, each with rupture of the symphysis pubis and
      sacroiliac joints during labor. All injuries were associated with significant
      initial pain and disability. All developed persistent symptoms related to the
      sacroiliac disruption. INTERVENTIONS: The three patients who had presented
      acutely were freated with closed reduction and application of a pelvic binder.
      Two underwent closed reduction of their pelvic dislocation while anesthetized
      with a general anesthetic. One patient (N.A.), who presented late, had not been
      treated with a binder. RESULTS: All four patients had persistent posterior pelvic
      (sacroiliac) pain. In two patients a postpartum neuropathy persisted.
      CONCLUSIONS: Severe pelvic dislocations are rare during labor, with conservative
      treatment reported to be successful in most cases. The persistence of symptoms in
      our patients emphasizes the need for careful examination and follow-up of these
      rare injuries. Because the outcome in our patients was poor and results in the
      literature are equivocal, we suggest the consideration of an operative approach
      to treatment in patients with symphyseal diastasis of > 4.0 cm.

PMID- 9258827
TI  - Functional treatment of humeral shaft fractures: indications and results.
AB  - OBJECTIVE: To determine effectiveness of closed functional bracing for humeral
      shaft fractures. DESIGN: Retrospective. SETTING: University. PATIENTS: Eighty
      seven patients with humeral shaft fractures. INTERVENTION: All patients were
      treated with closed functional bracing. MAIN OUTCOMES MEASURED: Both subjective
      and objective criteria were measured. Objective criteria consisted of range of
      motion and radiographic measurements. Subjective data were recorded using the
      Hannover Shoulder Score. RESULTS: Eighty-six percent of the follow-up group
      showed no restrictions in the movement of their shoulder and elbow joints. On the
      basis of subjective criteria, 95% of the patients were content with the
      functional treatment, 65% claimed to be pain free in their daily activities and
      at work, and 35% felt pain only when doing vigorous activities or heavy physical
      work. Although malposition with an angulation greater than 10 degrees was
      observed in ten patients (12.6%), functional outcome was good or excellent in two
      thirds of the cases followed up. CONCLUSIONS: When the correct indications are
      present, functional treatment of humeral shaft fractures has proven to be an
      excellent method that is both reliable and cost effective.

PMID- 9258828
TI  - The necessity of acute bone grafting in diaphyseal forearm fractures: a
      retrospective review.
AB  - OBJECTIVE: To determine the union rate of forearm fractures where acute bone
      grafting was recommended but not performed. DESIGN: Retrospective review.
      SETTING: Regional level one trauma center. PATIENTS: The criteria for inclusion
      in the study were patients with closed growth plates and a diaphyseal fracture of
      the radius, ulna, or both (including Monteggia and Galeazzi fracture
      dislocations) that were treated with plate fixation. Patients were excluded from
      the study if they were lost to follow-up before radiographic documentation of
      bone union. The review identified 198 fractures that were eligible for inclusion.
      Fifteen fractures were excluded. INTERVENTION: The method of treatment of each
      fracture was open reduction and plate fixation with or without bone grafting.
      MAIN OUTCOME MEASUREMENT: Fracture union. RESULTS: The overall union rate in
      comminuted, nongrafted forearm fractures (open and closed) was 98% (99/101; 95%
      confidence interval: 93-100%). The union rate in closed, comminuted, nongrafted
      forearm fractures was 97% (74/76; 95% confidence interval; 91-100%). CONCLUSIONS:
      Open reduction and internal fixation of comminuted diaphyseal forearm fractures
      without bone grafting in this study produced union rates comparable to those
      reported for open reduction and internal fixation of comminuted forearm fractures
      with acute bone grafting. This study suggests that routine use of bone grafting
      in comminuted forearm fractures is not indicated.

PMID- 9258830
TI  - Stereo fluoroscopy-assisted distal interlocking of intramedullary nails.
AB  - A simulation study of distal interlocking of an intramedullary nail was performed
      using newly devised, portable stereo fluoroscopy. Two intramedullary nails in
      which ten holes were drilled perpendicular to the long axis and at various angles
      to the diameter were inserted into a femoral and a tibial bone model. Ten drill
      bits were drilled freehand into the holes in the nail with the aid of the stereo
      fluoroscope. All twenty drill bits were seated in the holes in the first attempt.
      This instrument provides a three-dimensional view in real time, which enables the
      surgeon to appreciate the three-dimensional relationship between the drill bit
      and the hole in the nail in the bone model. Distal interlocking of the
      intramedullary nail is facilitated with the aid of this stereo fluoroscope.

PMID- 9258829
TI  - Radiocarpal articular pressures during the reduction of distal radius fractures.
AB  - OBJECTIVES: To measure in vivo radiocarpal articular pressures during closed
      reduction and external fixation of distal radius fractures. DESIGN:
      Intraoperative measurements using a sterile pressure sensitive sensor specially
      constructed for this application. SETTING AND PATIENTS: Ten patients with a
      closed distal radius fracture stabilized by radiometacarpal external fixation.
      Radiocarpal pressures measured during transarticular distraction, wrist palmar
      flexion, wrist ulnar inclination, and fracture reduction. MAIN OUTCOME
      MEASUREMENTS AND RESULTS: Transarticular distraction resulted in a substantial
      decrease of the articular pressure, averaging -158.1 mmHg. Palmar flexion
      resulted in a mean pressure increase of 91.8 mmHg. The reduction of the fracture
      using a combination of distraction, palmar flexion and ulnar deviation resulted
      in either an increase or decrease of articular pressure, but always with a
      tendency toward progressive normalization of the pressure, with a mean slope of
      3.2 mmHg/min. CONCLUSIONS AND CLINICAL RELEVANCE: The phenomena leading to the
      reduction of distal radius fractures could be related in part to a decrease of
      the intraarticular pressure, which may be responsible for a suction effect on the
      intraarticular bone fragments.

PMID- 9258831
TI  - Patellar tendon and tibial tubercle reconstruction using quadriceps tendon with
      patellar bone plug autograft.
AB  - This report describes a technique for the reconstruction of a patellar tendon
      tibial tubercle deficiency. This technique uses an easy-to-harvest, low-morbidity
      graft (autogenous quadriceps tendon), while allowing aggressive rehabilitation as
      a result of the strength of the graft.

PMID- 9258832
TI  - Segmental avascularity of the humeral diaphysis after reamed intramedullary
      nailing.
AB  - Although the clinical experience with reamed intramedullary nailing has been
      successful for the treatment of femur and tibia fractures, similar success has
      not been duplicated when this technique has been applied in the humerus. Although
      the cortical vascular response to nailing of the humerus is presently assumed to
      be similar to that of the femur, the response of the humerus to reaming has not
      been documented in vivo. The following case depicts avascularity of the humeral
      diaphyseal cortex as a complication of reamed intramedullary nailing and
      illustrates the sensitivity of the humerus to this treatment.

PMID- 9258833
TI  - Carpometacarpal dislocation of the thumb associated with ipsilateral fracture of
      the distal radius.
AB  - An acute carpometacarpal (CMC) dislocation of the thumb is itself an extremely
      rare injury, but one associated with a fracture of the distal radius has never
      before been reported. In our case, the fracture of the distal radius was treated
      by closed reduction and immobilization with a plaster cast, whereas the
      dislocation of the CMC of the thumb was treated with closed reduction,
      percutaneous fixation with Kirschner wires, and immobilization with a plaster
      cast. At the patient's two-year follow-up examination, the distal radius fracture
      displayed successful functional and radiographic results, but a subluxation of
      the CMC joint was evident.

PMID- 9258835
TI  - Prolonged arterial spasm in an ear replantation without venous anastomosis.
AB  - Successful ear replantations are rare. The authors report a case in which 75
      percent of the ear survived with an arterial anastomosis only. An extended period
      of time must be allowed for relief of arterial spasm in replants with tiny vessel
      diameters.

PMID- 9258834
TI  - Microsurgical reconstruction of the Achilles tendon with a fascia lata flap.
AB  - A case of total reconstruction of the Achilles tendon is reported. A compound
      free musculocutaneous unit of fascia lata was used to supply the absent tendon
      and soft tissues, achieving excellent cosmetic and functional results. This
      technique is suggested as an alternative for combating infection, providing soft
      tissue cover, and bridging the gap in the tendon.

PMID- 9258836
TI  - A new animal model to investigate axonal sprouting after end-to-side
      neurorrhaphy.
AB  - End-to-side neurorrhaphy is a technique that may provide a solution for the
      problem of distal target reinnervation without injury to the original donor
      nerve. The technique drew extensive attention after Viterbo reported his
      experiments in 1992; however, to date, the animal models used to elucidate the
      process of lateral axon sprouting had the disadvantage of substantial injury to
      the donor nerve, raising questions about the origin of axons reinnervating the
      nerve graft. In this report, a new model in the rat is introduced, in which the
      donor nerve is not damaged and an additional target can be innervated via a nerve
      graft. The saphenous nerve represents the axonal conduit; the proximal end is
      coapted end-to-side to the sciatic nerve at the site of a perineurial window. The
      distal end is passed through the adductor muscles and coapted distally in an end
      to-end fashion with the obturator nerve. In one group, a partial neurectomy was
      performed at the site of coaptation, which led to a lower Sciatic Functional
      Index (SFI). In the second group, the creation of a perineurial window yielded a
      normal SFI after end-to-side neurorrhaphy. Compared to the partial neurectomy
      group, the perineurial window end-to-side neurorrhaphy resulted in significantly
      less axons in the graft. The new model has the following advantages: (a) minimal
      injury to the donor nerve; (b) provision of a single additional target (gracilis)
      whose functional recovery can be assessed morphologically and behaviorally; (c)
      an opportunity to understand lateral sprouting by providing a non-injury model in
      which axonal invasion of the graft can originate from nodal axonal outgrowth; and
      (d) establishment of a noninjury model that can have widespread clinical
      applications.

PMID- 9258837
TI  - Lymphatic regeneration following microvascular limb replantation: a qualitative
      and quantitative animal study.
AB  - Lymphatic regeneration following unilateral hindlimb autotransplantation was
      studied in 14 Lewis rats using Technetium-99 radiolabeled sulfur colloid (TC-99)
      lymphoscintigraphy and compared to the lymphatic pattern exhibited in four
      unoperated control rats. Control animals demonstrate a reproducible flow of lymph
      along the deep lymphatic system from the foot, draining into the ipsilateral
      inguinal nodes, and then up to the para-aortic nodes. Following replantation,
      lymphatic outflow from the replanted limb begins to occur within 3 to 6 days,
      reaching normal lymphatic clearance within 12 days. However, the pattern of
      lymphatic flow is ill-defined, relying on multiple small channels of the
      superficial lymphatic system. In contrast to controls, at 3 hr post TC-99
      injection, lymphatic drainage in replanted rats is via the inguinal and axillary
      nodal regions bilaterally. This abnormal pattern persisted in the replanted
      animals for the duration of this study, 160 days. It is evident that lymphatic
      regeneration in this animal model is associated with a rapid return to normal
      levels of lymphatic clearance via collateral channels within the subcutaneous
      tissue. The rapidity with which lymphatic drainage is restored, and its
      localization within the subcutaneous tissue, can explain why replanted tissues
      and microvascular free flaps seldom develop lymphedema. In addition, the rat
      hindlimb replantation model may prove useful for studies of the general
      mechanisms and specific factors responsible for lymphangiogenesis.

PMID- 9258838
TI  - The rabbit dorsal flank flap.
AB  - The rabbit dorsal flank flap is useful for microvascular and flap research.
      Twenty-four rabbits were studied to assess the constancy and caliber of the blood
      supply to this flap. The sizes of the main pedicle vessels were measured in live
      animals. Lead oxide arteriograms were performed to assess the vascular pattern
      and territories. The pattern of supply was regular in over 85 percent (21) of the
      animals-a twin angiosome system, each territory being supplied from opposite ends
      of the flap and meeting in the central portion with choke anastamoses. Both
      proximal and distal territories were constantly supplied by a single large
      perforating vessel, the thoracodorsal vessels supplying a median of 59 percent of
      the flap, and the deep circumflex iliac vessels 41 percent. In three animals, a
      body wall perforator added a third flap territory, supplying a variable area
      ranging from 7 to 18 percent. The sizes of the vessels in each vascular pedicle
      were suitable for microvascular anastamosis, with the thoracodorsal vessels
      constantly larger (median size artery: 0.9 mm; vein: 1.2 mm) than the deep
      circumflex iliac vessels (median size artery: 0.7 mm; vein: 1.0 mm).

PMID- 9258839
TI  - Preservation of denervated muscle by sensory protection in rats.
AB  - The goal of this study was to determine whether sensory motor nerve crossover
      could alter post-denervation atrophy of skeletal muscle. Sixty adult Lewis rats
      were divided into three groups: 1) unilateral transection of the tibial nerve
      alone; 2) unilateral transection of the tibial nerve with immediate repair; and
      3) unilateral tibial and sural nerve transections with repair of the proximal
      sural nerve (sensory) to the distal tibial nerve (motor). The unoperated hind
      legs acted as positive controls. At 1 and 2 months postoperatively, posterior
      compartment musculature was harvested, weighed, then fixed and stained for
      histologic analysis. One month postoperatively, mean muscle weight in Group 1
      animals (transection alone) was 23.0 +/- 2.6 percent of the control side; for
      Group 2 animals (motor-motor repair) was 40.9 +/- 42 percent; and for the sensory
      protected Group 3 animals (sensory-motor repair) was 26.7 +/- 2.8 percent of
      controls (n = 15 per group). Two months postoperatively, the mean weights were
      14.5 +/- 0.9 percent, 58.8 +/- 7.3 percent, and 21.1 +/- 3.1 percent of controls
      for Groups 1, 2, and 3, respectively (n = 5 per group). Differences between
      groups were statistically significant. Histologic analysis of Group 1 specimens
      revealed generalized atrophy of all muscle fibers. In Group 2, specimens showed
      evidence of reinnervation and less atrophy. Group 3 specimens demonstrated an
      atrophic pattern with islands of non-atrophic fibers scattered throughout.
      Sensory protection was thus shown to have significant effect on post-denervation
      atrophy in rat skeletal muscle.

PMID- 9258840
TI  - Blood flow and microcirculatory changes in an ischemia-reperfusion injury model:
      experimental study in the rabbit.
AB  - This is the first in a series of studies designed to investigate the simultaneous
      changes in blood flow and microcirculation in an island flap during ischemia, in
      an ischemia-reperfusion model in the rabbit. An island groin flap based on the
      inferior epigastric vessels was harvested in 17 rabbits. The flap was rendered
      ischemic for 4 (n = 4), 6 (n = 4), and 16 (n = 9) hr by applying a microvascular
      clamp to both the inferior epigastric artery and vein. The blood flow in the
      epigastric artery and the microcirculation of the flap were monitored for 1 hr
      before the ischemia and for 3 hr after the ischemia period, using a transonic
      Doppler and a laser Doppler, respectively. Both the blood flow and the
      microcirculation of the flap were found significantly increased immediately after
      the ischemia in the 4- and 6-hr ischemia groups, compared to the pre-ischemic
      values. In the same groups, blood flow and microcirculation remained elevated
      over pre-ischemic levels, indicating a hyperemic response. In the 16-hr ischemic
      group, blood flow and microcirculation values remained significantly lower than
      the pre-ischemic readings at all points in time, demonstrating ischemia
      reperfusion injury.

PMID- 9258841
TI  - Differences between contractions of fast and slow muscles after nerve grafting.
AB  - The nature of reinnervation of fast- and slow-twitch skeletal muscles, as
      assessed by contractile characteristics, was determined in a rat sciatic-nerve
      graft model. The isometric contractile function of the fast-twitch plantaris and
      slow-twitch soleus muscles from hindlimbs of adult male Lewis rats (225 to 250 g)
      was assessed at 16 weeks after sciatic-nerve grafting. A 3-cm interposition
      sciatic-nerve graft was performed in the following groups: fresh syngeneic (n =
      10), fresh allogeneic (n = 11), 3-week stored allogeneic (n = 9), and freeze
      thawed allogeneic (n = 9). A control group consisted of 8 normal unoperated rats.
      Contractile properties were assessed by stimulating the muscles indirectly via
      the sciatic nerve. At 16 weeks, soleus and plantaris muscle masses were 40 and 52
      percent of controls, while their respective absolute tetanic forces (N) were less
      than 65 and 45 percent of controls. Analysis of time-dependent contractile
      parameters showed that the soleus/plantaris ratios for time to peak tension (TTP)
      and maximum rate of force development (df/dt) were not significantly altered
      following grafting. However, the ratio for half relaxation time (1/2RT) was
      significantly reduced from 4.44 +/- 0.62 toward a value of 1 following grafting.
      In this study, the authors found that, when fast and slow muscles were
      reinnervated from a common nerve, maintenance of differences in rate of force
      development supported selective reinnervation, while loss of differences in time
      of force relaxation supported random reinnervation.

PMID- 9258842
TI  - Upper-limb-to-lower-limb nerve transfer.

PMID- 9258843
TI  - Effect of goal difficulty, goal specificity and duration of practice time
      intervals on muscular endurance performance.
AB  - The aims of this study were to explore the relationships between goal
      specificity, goal difficulty and performance, and to determine if setting
      unrealistic goals would produce decreases in performance. The subjects were high
      school students from 15 schools and an attempt was made to control for the
      effects of social comparison. The schools were randomly assigned to one of 15
      conditions representing five levels of goal conditions-namely, 'do' (no goals),
      'do your best', 'improve by 10%' (easy), 'improve by 20%' (difficult/ realistic)
      and 'improve by 40%' (improbable/unattainable)-and three levels of practice
      duration (4, 6 and 8 weeks). This design consisted of nesting goal difficulty
      within practice duration, which enabled an examination of the goal specificity
      and goal attainability/difficulty hypotheses proposed by Locke and Latham (1985).
      A 5 x 3 factorial ANCOVA was applied to the post-baseline sit-up gain scores. The
      results indicated that all specific groups performed better than all non-specific
      groups. In addition, across practice durations the difficult/realistic group
      exhibited the greatest increase in performance, followed by the easy group. The
      performance gains of the improbable/unattainable group were substantially less
      compared with the difficult/ realistic group after 4 and 6 weeks, but not after 8
      weeks of practice. These results are in line with both the goal specificity and
      goal difficulty hypotheses derived from the application of Locke's goal-setting
      theory to sport.

PMID- 9258844
TI  - Dynamic-system analysis of opponent relationships in collective actions in
      soccer.
AB  - The aim of this study was to examine the contribution of the systemic approach to
      the analysis of play in team sports. We first focus on the theory of dynamical
      systems and consider the interactions between the main variables of the different
      components of systems and subsystems in soccer. In team sports, these variables
      represent fluctuating conditions, which momentarily constrain the organization of
      action for the players. Thus changes in the momentary configuration of the game
      have to be examined in the light of previous configurations, the outline of the
      defensive strategy and the tactical choices involved. To study this problem, we
      analyse the antecedents of goals in soccer. A procedure is proposed which
      analyses transitions between configurations of play, thus allowing time to be
      taken into consideration when studying the evolution of a match. To illustrate
      the use and benefit of the analytic procedure, two goals are described in terms
      of dynamic configurations of play and opportunity of choices made by attackers.

PMID- 9258845
TI  - Reasons for not exercising and exercise intentions: a study of middle-aged
      sedentary adults.
AB  - The aims of this study were to assess why people do not participate in exercise
      and physical activity, and what might lead them to become active. More
      specifically, we focused on the hindrances to entering the phase of transition
      from a sedentary to a more active lifestyle by analysing the reasons 265 middle
      aged Belgian adults gave for their inactivity. Their justifications were examined
      in relation to the conditions which they say would be needed for them to become
      more involved in regular physical activity. Factor analysis revealed that the
      reasons for inactivity referred to the adults' self-concept, to cognitive cost
      benefit based processes and to negative emotions associated with exercise. The
      conditions reported to be necessary to begin exercising referred to a perceived
      decrease in health and to the appropriateness of the exercise offered.
      Discriminant analysis showed that 'never-exercisers' differed from 'ex
      exercisers', and that within the subgroup of 'ex-exercisers' the long-term drop
      outs differed from the recent drop-outs. Cluster analysis revealed three types of
      sedentary adults: the unconcerned, the opposed and the approachable.

PMID- 9258846
TI  - Instrumentation of an ergometer to monitor the reliability of rowing performance.
AB  - The aim of this study was to develop a portable data-acquisition system to
      measure the stroke-by-stroke power output and the force developed at the feet
      during simulated rowing, and to use the system to investigate the reliability of
      selected variables used to describe rowing performance. Using a Concept II rowing
      ergometer, the instantaneous power output was calculated as the product of the
      force at the handle, measured using a small transducer mounted near the handle,
      and the velocity of the handle, measured using an infra-red emitter-receiver to
      detect the passage of each vane of the flywheel. The cumulative force at the feet
      was measured using two force-plates, one mounted under each foot. The outputs
      from all transducers were sampled at 30 Hz using an 80386SX computer running
      Asyst data-acquisition software. Excellent linearity in all transducers was
      established and a calibration of the system revealed measurement errors of less
      than 3%. The reliability of the variables used to describe rowing performance was
      studied using a repeated 90 s maximal test on seven experienced oarsmen.
      Statistical analysis indicated that, of the 14 variables used, only two failed to
      meet the set criterion. In conclusion, it was found that a rower's performance
      during simulated rowing was very reliable and that the selected variables used in
      this study could be used to objectively describe performance on a rowing
      ergometer.

PMID- 9258847
TI  - Effects of the type of recovery training on the concentric strength of the knee
      extensors.
AB  - The aim of this study was to examine the effects of specific concentric and
      eccentric training on concentric muscular strength following an initial
      standardized period of excessive training that combined concentric and eccentric
      actions. For a period of 12 weeks, 37 young elite female basketball players
      performed standardized training, which included concentric and eccentric actions
      at 70% and 110% of one-repetition maximum (1-RM), respectively. They were then
      divided into three groups that followed 12 week programmes which included
      concentric (C-E/C, n = 13), eccentric (C-E/E, n = 13) or a combination of both
      concentric and eccentric (C-E/-E, n = 11) exercises. The standardized and
      specific training programmes consisted of 16 and 8 sets of eight repetitions
      respectively, performed four times a week. Eleven players who did not participate
      in either the standardized or specific training programmes served as controls (n
      = 11). Following the initial 12 weeks of standardized training, the concentric
      strength of the knee extensors was evaluated isokinetically and using leg-press
      and squat-jump tests. Significant (P < 0.05) reductions in isokinetic torque, and
      leg-press and squat-jump performance, were seen. The C-E/C group showed
      significant (P < 0.05) increases in isokinetic torque, and leg-press and squat
      jump performance, after 24 weeks of training when compared with pre-training
      values. Conversely, no significant differences were noted for the C-E/E and C-E/C
      E groups. These findings confirm the mode specificity principle, as only the
      concentric specific training programme improved the concentric strength of the
      knee extensors.

PMID- 9258848
TI  - Controlling locomotion during the acceleration phase in sprinting and long
      jumping.
AB  - The production of a stabilized locomotor pattern is crucial in sporting
      activities such as the run-up in long jumping, a task which is characterized by
      high spatio-temporal constraints. The aims of this study were as follows. First,
      we wished to investigate how athletes stabilize their stride patterns so as to
      strike the take-off board accurately. Previous studies have argued that during
      the initial accelerative phase of the run-up, athletes attempt to produce a
      stereotyped stride pattern. We investigated this initial phase in more detail by
      examining the kinematic parameters of long jumpers' strides and their spatial
      consequences. These data were then compared with the stride patterns observed in
      a sprinting task, which did not impose the same spatio-temporal constraints. Our
      second aim was to compare the stride patterns of skilled and unskilled jumpers.
      Kinematic stride parameters were measured in two ways. The temporal parameters
      (flight time, stance time) were recorded by a microcomputer attached to the
      athlete, whereas the spatial parameters (stride length) were measured directly
      from the footprints the subjects made on the track. The results confirmed those
      of previous studies, showing that long jumpers initiate locomotor adjustments in
      the last 3-4 strides before take-off, but a more detailed analysis revealed that
      long jumping is characterized by adjustments during the first few strides. These
      adjustments were not seen in the sprinting task, where systematic variations of
      accumulated error were observed. These stride adjustments differed from those
      seen in previous studies and thus permit a more comprehensive understanding of
      the control involved in the tasks studied. The patterns exhibited by the skilled
      and unskilled subjects were very similar overall, but differed in that variations
      in accumulated error were less marked for the skilled subjects, who tended to
      make early stride adjustments sooner than the unskilled subjects. These results
      are discussed in relation to the cognitive and ecological approaches to movement
      coordination.

PMID- 9258849
TI  - The ability of tests of muscular function to reflect training-induced changes in
      performance.
AB  - We examined the ability of isokinetic and isoinertial tests of muscular function
      to track training-induced changes in performance. Subjects completed the
      following tests before and after training: (1) two isoinertial tests using
      concentric and eccentric actions; (2) isokinetic knee extension at two
      velocities; and (3) a one-repetition maximum squat. Further, a 40 m sprint and 6
      s cycle test were conducted as measures of athletic performance. The subjects
      were split into a weights group, which performed heavy squats, and a control
      group. The results showed that training significantly enhanced sprint time by
      2.2%, and the improvement in cycle performance (9%) approached significance (P =
      0.09). However, apart from the squat, no measure of muscular function
      significantly changed because of training. Furthermore, there was no relationship
      between the training-induced changes in performance and the training-induced
      changes in the isokinetic and isoinertial tests. The results suggest that tests
      of muscular function cannot be used to monitor training-induced changes in
      performance. We considered this to be due to the large degree of variance
      unaccounted for in the relationship between the scores on tests of muscle
      function and performance. Therefore, the effectiveness of training should be
      based on changes in performance rather than changes in test scores of muscle
      function.

PMID- 9258850
TI  - Effect of the number of preceding muscle actions on subsequent peak power output.
AB  - Many sports events require participants to exert a maximal effort in the closing
      stages-that is, after prior fatiguing exercise. Peak and mean pedalling rate
      during 30 s of high-intensity cycle ergometer exercise was manipulated by
      altering the applied resistance or the initial exercise intensity so that the
      effect of three contrasting strategies on subsequent peak power output could be
      examined. Seven female students cycled for 30 s in one of three conditions: (1)
      all-out effort against an applied resistance of 7.5% of body weight (test 1); (2)
      at a constant pace of 55% of the peak pedal rate of test 1 against a resistance
      of 10.9 +/- 0.4% of body weight (test 2); (3) all-out effort against the greater
      resistance (test 3). A 6 s sprint against the lesser resistance was performed 3 s
      after each test. Total work was greater (P < 0.01) in test 3 than in test 1,
      while mean pedal rate was higher (P < 0.01) in test 1 (mean +/- S.E.: 10.0 +/-
      0.4 rad s-1) than in tests 2 and 3 (7.2 +/- 0.4 and 7.8 +/- 0.3 rad s-1
      respectively). The peak power output in the subsequent 6 s sprint was similar
      following tests 2 and 3 (516 +/- 37 and 534 +/- 41 W respectively), but was lower
      following test 1 (420 +/- 37 W) (P < 0.01, test 1 vs tests 2 and 3). These
      results indicate that the number of muscle actions during 30 s of fatiguing
      exercise may exert a considerable influence on one's ability to subsequently
      produce peak power output. In sports such as cycling where the same external
      velocity is attainable at different muscle action speeds, then appropriate gear
      selection during the race will impact on the rider's ability to sprint in the
      latter stages.

PMID- 9258851
TI  - Accumulated oxygen deficit and shuttle run performance in physically active men
      and women.
AB  - The aim of this study was to establish the validity of using shuttle run
      performance over 20 m to predict accumulated oxygen deficit. A new high-intensity
      shuttle run test (HIST) was devised, during which subjects ran to exhaustion at a
      speed equivalent to 120% of their performance attained during a progressive
      shuttle run test. The reliability of the new test was examined and found to be
      acceptable for 18 subjects who performed the test twice on separate days (r =
      0.84, P < 0.01, study I). The discriminating ability of the new test was examined
      by comparing the distance covered by eight sprint- and eight endurance-trained
      athletes at 120% of their respective progressive shuttle run performances (615 +/
      111 vs 273 +/- 84 m, P < 0.01, study II). The strongest predictor of accumulated
      oxygen deficit for 27 subjects was found to be the geometric mean of the
      performances on the new test and on the progressive shuttle run test (r = 0.74,
      study III). The regression equation for this relationship was then used to
      estimate the accumulated oxygen deficit for a second group of 16 subjects (study
      IV). The correlation between the estimated and measured accumulated oxygen
      deficits was significant (r = 0.79, P < 0.01). The results from studies III and
      IV were therefore combined with the data from six new subjects to give a
      regression equation for predictive purposes based on 49 subjects.

PMID- 9258852
TI  - Exercise-induced skeletal muscle damage and adaptation following repeated bouts
      of eccentric muscle contractions.
AB  - Repeated bouts of eccentric muscle contractions were used to examine indirect
      indices of exercise-induced muscle damage and adaptation in human skeletal
      muscle. Twenty-four subjects (18 females, 6 males) aged 20.0 +/- 1.4 years (mean
      +/- S.D.) performed an initial bout of either 10 (n = 7), 30 (n = 9) or 50 (n =
      8) maximum voluntary eccentric contractions of the knee extensors, followed by a
      second bout of 50 contractions 3 weeks later using the same leg. Muscle soreness
      was elevated after all bouts (P < 0.05, Wilcoxon test), although the initial bout
      reduced the soreness associated with the second bout. Force loss and a decline in
      the 20:100 Hz percutaneous electrical myostimulation force ratio were observed
      after all exercise bouts (P < 0.01). Serum creatine kinase activity was elevated
      following the initial bouts of 30 and 50 repetitions (P < 0.01), but there was no
      increase following 10 repetitions. No increase in serum creatine kinase activity
      was observed in any group following the second bout of contractions (P > 0.05).
      We conclude that skeletal muscle adaptation can be brought about by a single bout
      of relatively few eccentric muscle contractions. Increasing the number of
      eccentric muscle repetitions did not result in an increased prophylactic effect
      on skeletal muscle.

PMID- 9258853
TI  - Carbohydrate ingestion improves endurance performance during a 1 h simulated
      cycling time trial.
AB  - This study examined the effect of carbohydrate ingestion on metabolic and
      performance-related responses during and after a simulated 1 h cycling time
      trial. Eight trained male cyclists (VO2 peak = 66.5 ml kg-1 min-1) rode their own
      bicycles mounted on a windload simulator to imitate real riding conditions. At a
      self-selected maximal pace, the cyclists performed two 1 h rides (separated by 7
      days) and were fed either an 8% carbohydrate or placebo solution. The beverages
      were administered 25 min before (4.5 ml kg-1) and at the end (4.5 ml kg-1) of the
      ride. With carbohydrate feeding, plasma glucose tended (P = 0.21) to rise before
      the time trial. Compared with rest, the plasma glucose concentration decreased
      significantly (P < 0.05) at the end of both rides, with no statistically
      significant difference being observed between treatments. Thereafter, plasma
      glucose increased significantly (P < 0.05) at 15 and 30 min into recovery and was
      significantly higher at 30 min during the carbohydrate trial compared with the
      placebo trial. No significant changes in plasma free fatty acids were observed
      during the ride. However, a significant increase (P < 0.05) in free fatty acids
      was found at 15 and 30 min into recovery, with no difference between trials. Mean
      power output was significantly (P < 0.05) greater during the carbohydrate
      compared with the placebo trial (mean +/- S.E.: 277 +/- 3 and 269 +/- 3 W,
      respectively). The greater distance covered in the carbohydrate compared with the
      placebo trial (41.5 +/- 1.06 and 41.0 +/- 1.06 km, respectively; P < 0.05) was
      equivalent to a 44 s improvement. We conclude that pre-exercise carbohydrate
      ingestion significantly increases endurance performance in trained cyclists
      during a 1 h simulated time trial. Although the mechanism for this enhancement in
      performance with carbohydrate ingestion cannot be surmised from the present
      results, it could be related to a higher rate of carbohydrate oxidation, or to
      favourable effects of carbohydrate ingestion on the central component of fatigue.

PMID- 9258854
TI  - Integrating substance abuse treatment for the seriously mentally ill into
      inpatient psychiatric treatment.
AB  - This paper offers guidelines for the assessment and treatment of substance abuse
      problems in seriously mentally ill persons who are admitted into inpatient
      psychiatric treatment. This approach has been used successfully by the authors
      and may be most useful in settings where a specialized dual-diagnosis treatment
      program is not feasible. The first step consists of identifying potential
      substance abusers using several sources of information including the patient's
      record, a brief patient interview, and an interview with the patient's family and
      caseworker. Patients who have a confirmed or suspected substance abuse problem
      undergo a substance abuse assessment designed to evaluate consumption patterns,
      the negative consequences of substance use, and high-risk situations for alcohol
      and drug use. Patients are then presented with individualized feedback in a non
      coercive manner, which is intended to increase their motivation to change their
      substance-use behavior. Treatment consists of a structured coping skills group
      which covers nine specific topics. The topics covered in the group treatment
      include both general social skills and specific drug and alcohol coping skills
      intended to assist individuals in coping effectively with high-risk situations.
      The content of each group session is described along with guidelines for
      conducting coping skills group treatment with the seriously mentally ill.

PMID- 9258855
TI  - The Wheel Project. Women Helping to Empower and Enhance Lives.
AB  - The Women Helping to Empower and Enhance Lives (WHEEL) Project focused on female
      sexual partners of injection drug users (i.d.u.s). It was conducted in five
      sites, three within and two outside the continental United States. The study's
      two main intervention goals were to (a) reduce HIV-related sexual risk behaviors
      and (b) reduce HIV-related drug risk behaviors. The Project also featured needs
      assessment, planning, and staff training components. Baseline data were collected
      on 2,794 women, which made this the largest study of noninjecting female sexual
      partners of i.d.u.s in the United States. Six-month follow-up data were obtained
      on 1,953 women. The Wheel Project tested two interventions: an individual
      intervention and a group intervention. The study found significant reductions in
      drug use and risky sexual behaviors for the 6-month follow-up sample for both
      interventions. These changes were substantial and point to the viability of both
      interventions for this population of sexual partners of injection drug users.

PMID- 9258856
TI  - The course of depressive symptoms over time for women who completed drug
      treatment.
AB  - The purpose of the present study was to (a) describe the trend in depressive
      symptoms in a sample of postpartum women who used cocaine and who completed drug
      treatment; and (b) to examine possible correlates of those trends including
      treatment type and selected pretreatment characteristics. Self-reported levels of
      depressive symptoms improved from treatment entry to discharge and remained
      relatively stable through three postdischarge follow-up points. Baseline level of
      depression was the only pretreatment factor that was correlated with the trend in
      depressive symptoms. And length of time in treatment, previous drug treatment,
      and baseline severity of drug use were not.

PMID- 9258857
TI  - Ethnic differences in the treatment of dual mental and substance disorders. A
      preliminary analysis.
AB  - Differences between white and ethnic client psychosocial functioning, psychiatric
      and substance abuse symptomatology, and service utilization costs from a
      longitudinal clinical trial examining the relative cost effectiveness of three
      specialized interventions for dual disorders are compared within the study sample
      and to the existing literature. Ethnic clients comprised 30% of the treated
      sample, had lower psychosocial functioning scores (rated and self-reported), and
      received less supportive treatment services during the first 6 months of the
      intervention program; however, their overall outcomes were equivalent to those of
      white clients at 6 months. There were no functioning or symptom outcome
      differences across the three treatment groups, but the 12-step group had the
      highest intensive and supportive service costs over time, and also the greatest
      reductions in intensive service costs after 6 months. Clinical issues are
      described and the clinical implications for more effectively serving dually
      diagnosed ethnic clients are outlined.

PMID- 9258858
TI  - Rethinking patient placement: the human service matrix model for matching
      services to needs.
AB  - The improvements in both clinical and fiscal outcomes necessary for prosperity in
      the current healthcare environment require a rethinking of our conceptual
      approaches to patient assessment, treatment planning, and service delivery.
      Conventional practice rests in part on the Level of Care concept, which assigns
      intensities of both clinical services and treatment settings in a linked manner
      according to impairment severity. Although this approach has resulted in more
      efficient matching of resources to needs, it is overly restrictive, and does not
      speak directly to the need to match both healthcare and social services
      (including treatment setting) to human needs for treatment to be successful. The
      Human Service Matrix model presented in this article delinks clinical from social
      services and creates a conceptual framework for integrating social and healthcare
      services in the cure of patients with addictions. Our experience with this model
      suggests it has heuristic value in promoting cost and outcome effective
      treatment.

PMID- 9258859
TI  - Effects of gamma-hydroxybutyric acid (GHB) in opioid-dependent patients.
AB  - Gamma-hydroxybutyric acid (GHB) is a GABA metabolite used clinically for sleep
      induction. The abuse liability of GHB is controversial. As part of a study of the
      effect of GHB pretreatment on naloxone-precipitated opiate withdrawal, eight
      opioid-stabilized subjects received a balanced, randomized, double-blind sequence
      of oral placebo, GHB 15 mg/kg and 30 mg/kg. GHB had no consistent physiological
      effects. After GHB and prior to naloxone, subjects rated "sluggish," "spaced,"
      "carefree," and "good-mood" higher after GHB 30 mg/kg than after placebo.
      Subjects identified the 30 mg/kg dose as most similar to placebo (n = 3),
      benzodiazepine (n = 2), opiate (n = 2), and alcohol (n = 1).

PMID- 9258860
TI  - An inpatient profile of patients with a substance abuse diagnosis in Maryland.
AB  - We provide a descriptive analysis of patients with a substance abuse diagnosis in
      Maryland hospitals in 1991. The intent of the study was not to model
      relationships between substance abuse and other outcomes (e.g., length of stay),
      but was to obtain a better understanding of the population receiving inpatient
      care and to motivate future research. We found that the majority of patients with
      a substance abuse diagnosis were male, African-American, single, and between the
      ages of 15 and 44. Medicaid was overwhelmingly the primary payer for their care.
      These patients were diagnosed with chronic liver disease, pancreas diseases, HIV
      infection, a number of psychiatric disorders, and respiratory symptoms. We
      surprisingly found that the average length of stay was shorter for patients with
      a substance abuse diagnosis and that their average charges were only slightly
      higher than other patients. We also found that substance abuse patients enter the
      hospital through the emergency room and the majority leave the hospital against
      medical advice.

PMID- 9258861
TI  - Assessing substance abuse treatment provider training needs: screening skills.
AB  - Screening instruments for substance abuse can be expeditious and effective
      clinical tools. A training needs assessment conducted with a randomly selected
      sample of substance abuse treatment providers (n = 1684) in licensed facilities
      in New England identified the adequacy of training, interest in training,
      clinical skill, and training need in the use of 13 substance abuse screening
      instruments. The results revealed that New England substance abuse treatment
      providers are not skilled in the use of screening instruments and have a high
      level of training need in this area. Differences in screening skill were found
      among the New England states. In addition, women and those with less treatment
      experience have lower screening skill; similarly, women, those having less
      experience in the field, and social workers and nurses evidenced higher training
      need in screening. The discussion considers skill, adequacy of training, training
      interest, and training need. The conclusion suggests that one approach to the
      coexisting increased need for screening skills due to managed care requirements
      and the lack of interest in these skills is to study managed care marketplace
      demands to determine training priorities.

PMID- 9258862
TI  - Addressing women's concerns about weight gain due to smoking cessation.
AB  - Specific concerns about weight gain following smoking cessation inhibit attempts
      to quit smoking, especially in women. However, adjunct interventions to prevent
      weight gain after cessation have generally been successful only in attenuating,
      rather than preventing, weight gain. More aggressive weight control adjuncts may
      be necessary to prevent cessation-induced weight gain. On the other hand, weight
      control programs have not been found to improve long-term smoking abstinence and,
      in fact, may actually impede abstinence, necessitating a search for alternative
      approaches to addressing weight concerns. Since the typical amount of weight gain
      is essentially trivial from a health standpoint, particularly when compared with
      the health benefits of quitting smoking, the most appropriate clinical strategy
      may be to combat the weight concerns themselves rather than the weight gain. A
      second alternative approach is to focus all treatment efforts on smoking
      cessation alone, to avoid placing excessive burdens on participants resulting
      from attempting simultaneous changes in multiple health behaviors (i.e., smoking
      and those related to weight). The rationales for these three clinical approaches
      to addressing concerns about weight gain-more effective weight control, direct
      reduction in weight concerns by cognitive-behavioral treatment, and smoking
      cessation only-are presented, followed by descriptions of the adjunct treatments
      based on these approaches currently being evaluated in a clinical outcome study
      with women trying to quit smoking.

PMID- 9258863
TI  - A qualitative study of barriers to formal treatment among women who self-managed
      change in addictive behaviours.
AB  - Alcohol and drug abuse and dependence are common disorders in our society, and
      the vast majority of those who recover do so without formal treatment. Although
      this phenomenon appears to be more common among women than men there has been no
      gender-sensitive research. This qualitative study explored the barriers to formal
      treatment seeking among women who self-managed change in their alcohol and other
      drug dependence. The principal barriers identified included social stigma and
      labelling; lack of awareness of the range of treatment options, concerns about
      childcare, the perceived economic and time costs of residential treatment,
      concerns about the confrontational models used by some treatment services, and
      stereotypical views of clients of treatment services. A number of recommendations
      were made regarding program reach and content.

PMID- 9258864
TI  - Characteristics and treatment needs of sexually abused pregnant women in drug
      rehabilitation. The Massachusetts MOTHERS Project.
AB  - Four hundred forty-seven Medicaid-eligible pregnant chemically dependent women
      were interviewed during their stay in publicly funded detoxification centers in
      Massachusetts. One hundred eighty-four women (41%) reported sexual abuse during
      their lifetime. Sexually abused women differed significantly from women who had
      not been abused, on a variety of psychological, social, and medical problems
      indicators. Sexually abused women appear to constitute a specific subgroup of the
      larger population of substance abusing women, and have unique treatment needs.

PMID- 9258865
TI  - Training in substance abuse: still a stepchild in psychiatry residencies?

PMID- 9258866
TI  - Preliminary evidence for the evolution in complexity of heart rate dynamics
      during autonomic maturation in neonatal swine.
AB  - Previous studies suggest that the autonomic nervous system plays an important
      role in the generation of complex heart rate dynamics. Therefore, we hypothesized
      that the complexity (irregularity) of cardiac interbeat intervals would evolve
      with the maturation of autonomic innervation to the heart. Twelve healthy newborn
      piglets were implanted with ECG transmitters and studied at one or more different
      ages up to 33 days of age, the period during which pigs develop functional
      sympathetic innervation of the heart from the stellate ganglia. Three animals
      underwent right stellate ganglionectomy, two a left stellate ganglionectomy, two
      a right cardiac vagotomy and five a sham procedure. The statistic, approximate
      entropy (ApEn), was used to quantify the regularity of interbeat interval
      fluctuations. Sham-operated animals showed an increase in the standard deviation
      (SD) and irregularity (ApEn) of cardiac interval fluctuations with increasing
      age. Right stellate ganglionectomized piglets had lower interbeat interval ApEn
      values, but similar SD's by 26-27 days of age compared to sham-operated animals.
      Left stellate ganglionectomy, which affects cardiac inotropy rather than
      chronotropy, had no effect on cardiac interval irregularity, while vagotomy had
      an indeterminant effect. The increasing irregularity of interbeat interval
      dynamics during autonomic maturation and the apparent attenuation of heartbeat
      irregularity when right stellate ganglion innervation is interrupted, provides
      empirical support for the notion that complex heartbeat dynamics in the mature
      animal are the result of a network of autonomic neural pathways that enables an
      organism to adapt to stress.

PMID- 9258867
TI  - Simultaneous cardiac and renal sympathetic neural responses to activation of left
      ventricular sympathetic afferents.
AB  - In separate sets of experiments, we observed that activation of left ventricular
      sympathetic afferents by transmural myocardial ischemia (TMI) appeared to elicit
      greater reflex increases in efferent sympathetic nerve activity (SNA) to the
      heart than to the kidney. To assess this observation more rigorously, we
      simultaneously measured changes in cardiac and renal SNA elicited by TMI and by
      epicardial and intracoronary bradykinin (BK). Experiments were performed in 19
      chloralose-anesthetized dogs with sinoaortic denervation and vagotomy. TMI was
      created by a 2 min complete occlusion of the anterior descending coronary artery
      while a collateral flow limiting stenosis was present on the circumflex coronary
      artery. Epicardial BK was applied to small sponges (1 cm2) which were placed on
      the anterior wall of the left ventricle. Intracoronary BK was injected into a
      branch of the anterior descending artery. We observed that mean maximal reflex
      increases in SNA during TMI and intracoronary BK were significantly greater in
      cardiac than in renal nerves (TMI; 58 +/- 11% versus 36 +/- 9%, p = 0.01;
      intracoronary BK; 144 +/- 48% versus 77 +/- 26%, p = 0.05). Epicardial BK
      elicited reflex increases in cardiac and renal SNA which were not significantly
      different (167 +/- 44% versus 127 +/- 36%; p = 0.72). Our results indicate that
      activation of left ventricular sympathetic afferents by TMI and intracoronary BK
      elicits greater reflex increases in sympathetic outflow to the heart than to
      other end-organs such as the kidney. We speculate that these augmented excitatory
      responses are most likely related to engagement of cardio-cardiac spinal
      sympathetic reflexes during intense stimulation of sympathetic afferent endings.

PMID- 9258868
TI  - Postnatal development of the pulmonary neuroepithelial bodies in various animal
      species.
AB  - Various aspects of the postnatal development of intrapulmonary neuroepithelial
      bodies (NEB) were quantified in guinea-pigs, rabbits, cats, rats and hamsters.
      The highest densities of NEB were found at birth, especially in species with very
      immature neonates. Postnatally this density decreased, most probably by lung
      expansion and growth. The number of corpuscular cells per NEB generally did not
      change during postnatal development. Likewise, the volume density of their
      secretory dense cored vesicles remained unchanged. On the other hand, in most
      species and especially in those with very immature neonates, the number of
      intracorpuscular NEB nerve endings increased during postnatal development. At the
      same time, the number of afferent nerve endings increased at the expense of the
      efferent ones. We argue that NEB serve a dual function: endocrine and
      chemoreceptor. The endocrine function, dependent on the number of cells and their
      content of secretory vesicles, is already well developed at birth and does not
      mature further. The chemoreceptor function, dependent on the innervation, shows
      considerable maturation in the postnatal period.

PMID- 9258869
TI  - Postnatal ontogeny of glutamate receptors in the rat nucleus tractus solitarii
      and ventrolateral medulla.
AB  - The nucleus tractus solitarii and the ventrolateral medulla are two brainstem
      regions involved in regulation of autonomic functions. Glutamate (Glu) receptors
      localized within these two regions play a key role in neural control of
      swallowing and breathing and in blood pressure regulation. In the present study,
      postnatal changes in global [3H]Glu binding and in [3H]Glu binding to N-methyl-D
      aspartate (NMDA) receptors were analyzed in the nucleus tractus solitarii and the
      ventrolateral medulla using in vitro receptor autoradiography. Similar results
      were obtained in both regions. When expressed as density values (fmol/mg tissue),
      both global and NMDA-sensitive Glu binding increased by approximately 50-70%
      between birth and postnatal day 9 (P9) and then decreased until P30. When
      expressed as binding per nucleus (i.e., after correction for tissue growth),
      global Glu binding still increased between birth and P9 and decreased between P9
      and P30 whereas NMDA-sensitive binding increased until P9 and remained stable
      thereafter. Saturation studies showed a postnatal increase in Glu receptor number
      per nucleus, which occurred mainly between birth and P9, and a decrease in Glu
      receptor affinity between P9 and adulthood. These results indicate that dramatic
      changes in glutamatergic neurotransmission occur in the nucleus tractus solitarii
      and the ventrolateral medulla during the first month of postnatal life. They
      suggest that both neonates and young animals may not be fully mature as regard to
      central regulation of autonomic functions.

PMID- 9258870
TI  - Expression of neuropeptides and nitric oxide synthase in neurones innervating the
      inflamed rat urinary bladder.
AB  - Micturition reflexes become hyperexcitable with the development of a cystitis. In
      the present study the question is addressed, whether alterations in the
      expression of neuropeptides and nitric oxide synthase (NOS) in the neuronal
      pathways to the bladder may be involved in the hyperexcitability. Primary sensory
      neurones in the dorsal root ganglia (DRG) L1, L2, L6 and S1 as well as
      postganglionic efferent neurones in the major pelvic ganglia (MPG) that innervate
      the rat urinary bladder were labeled with retrogradely transported Fast Blue
      (FB). Immunocytochemical techniques were used to determine alterations in the
      expression of calcitonin gene-related peptide (CGRP), substance P (SP), galanin
      (GAL) and NOS in these neurones following mustard oil-induced inflammation of the
      urinary bladder. Instillation of 2.5% mustard oil into the bladder led to a
      massive leukocyte infiltration of the vesical tissues, partial damage of the
      mucosal layer and a marked hyperreflexia of the detrusor muscle. 48 h after
      induction of the cystitis the proportion of FB-labeled bladder afferent neurones
      that expressed CGRP and SP were significantly increased in both the rostral
      lumbar DRGs (L1, L2) and the lumbosacral DRGs (L6, S1) (CGRP, +15-38%; SP, +47
      158%) as compared to control animals. However, there was a differential effect of
      the inflammation on the expression of GAL and NOS in bladder afferents at the two
      segmental levels examined. Significant alterations in the number of FB-labeled
      afferents exhibiting GAL immunoreactivity were mainly restricted to the
      lumbosacral DRGs L6 (+169%) and S1 (+60%). On the contrary, the proportion of NOS
      immunoreactive bladder afferents significantly increased only in the rostral
      lumbar DRGs L1 (+144%) and L2 (+193%), while the level of NOS-expression was
      unaffected at the lumbosacral levels. Inflammation furthermore induced a
      significant increase (+275%) in the number of FB-labeled neurones in the MPGs
      that exhibited NOS immunoreactivity. These results indicate that an upregulation
      of CGRP-, SP-, GAL- and NOS-synthesis in sensory and efferent neurones is
      involved in the response to an acute cystitis. Because of the differences in the
      segmental pattern and degree of upregulation of these substances in bladder
      afferents that project to the rostral lumbar and lumbosacral spinal cord a
      different regulation of the sympathetic and parasympathetic efferent outflow to
      the urinary bladder is suggested. The involvement of CGRP, SP, GAL and NOS in the
      modulation of both excitatory and inhibitory mechanisms that control the cystitis
      induced detrusor hyperreflexia is discussed.

PMID- 9258871
TI  - Electrophysiological evidence of ipsilateral reno-renal reflexes in the cat.
AB  - To verify the existence of ipsilateral reno-renal reflexes we studied the effect
      of surgical denervation of one kidney on the ipsilateral efferent renal nerve
      activity (ERNA), in the absence of contralateral afferent renal nerve activity.
      Thus the ipsilateral renal denervation was performed 1 h later than the
      contralateral renal denervation. The experiments were done on 9 anesthetized
      cats. Arterial pressure, urine flow rate (UFR) of both kidneys and ERNA to the
      ipsilateral kidney were measured. All variables were monitored during a 3 min
      control period and for 13 min after either contralateral and ipsilateral renal
      denervations. ERNA significantly increased (+20 +/- 9%) and UFR concomitantly
      decreased (-11 +/- 10%) after the surgical denervation of the contralateral
      kidney which showed an increase (+91 +/- 19%) in UFR. The subsequent ipsilateral
      denervation caused a significant increase in UFR (+117 +/- 25%) and ERNA (79 +/-
      23%) of the same kidney, while on the opposite side UFR did not change. During
      the two procedures, arterial pressure did not change. Our data demonstrate the
      existence of ipsilateral reno-renal reflexes that exert a tonic inhibitory effect
      on ipsilateral ERNA.

PMID- 9258872
TI  - Morphological relations between haem oxygenases, NO-synthase and VIP in the
      canine and feline gastrointestinal tracts.
AB  - Carbon monoxide (CO), produced by haem oxygenase (HO), has been suggested as a
      messenger molecule in the central and peripheral nervous systems. In the present
      study, we have investigated the occurrence of the two isoforms of HO, HO-2 and HO
      1 in the canine and feline gastrointestinal tracts, including the small and large
      intestine and the gastrointestinal sphincters. An abundance of nerve cell bodies
      that contained immunoreactivity for HO-2 was found in the submucosal and
      myenteric plexuses. HO-2 immunoreactivity was frequently co-localized with nitric
      oxide synthase (NOS) or vasoactive intestinal peptide (VIP) immunoreactivities
      and was also observed in some nerve fibres, certain non-neuronal cells dispersed
      among smooth muscle bundles, and in vascular endothelium. The antiserum against
      HO-1 revealed immunoreactivity in nerve cell bodies in the enteric plexuses, in
      nerve fibres and in non neuronal cells in the smooth muscle layers. Some of the
      nerve structures were also NOS- or VIP-immunoreactive. These results demonstrate
      the presence of HO isoenzymes in nerves and other structures of the canine and
      feline gastrointestinal tracts and support the view that CO may have a role as a
      messenger molecule in the enteric nervous system.

PMID- 9258873
TI  - Cytochrome oxidase staining in the major pelvic ganglion of the male rat.
AB  - Cytochrome oxidase staining was used as a marker of metabolic activity in neural
      elements in the rat major pelvic ganglion. Many neurons in the ventral pole of
      the ganglion have little cytochrome oxidase activity, while neurons in other
      locations show gradations in staining intensity. Punctate staining around
      principal neurons may represent preganglionic terminals, since it was greatly
      reduced after denervation of the ganglion. Image analysis was used to compare
      neuronal size to staining intensity. There was a negative correlation between
      cell size and staining intensity; the largest neurons were only lightly stained
      for cytochrome oxidase, while the medium and the small neurons showed a full
      range of metabolic activity. To study metabolic activity of an identified
      neuronal population, the seminal vesicles were injected with a retrograde tracer.
      The largest seminal vesicles neurons (1500 to 3200 microns2) had low enzyme
      activity, whereas the majority of neurons to this organ were smaller with
      gradations in staining. These results are indicative of the metabolic activity of
      the autonomic innervation to various pelvic tissues. Cytochrome oxidase
      histochemistry should prove valuable in assessing the demands placed on autonomic
      ganglia in differing functional and dysfunctional states.

PMID- 9258874
TI  - Strengthening research in Departments of Obstetrics and Gynecology.

PMID- 9258875
TI  - Effects of hypoxemia on 11 beta-hydroxysteroid dehydrogenase types 1 and 2 gene
      expression in preterm fetal sheep.
AB  - OBJECTIVE: To examine the effect of sustained hypoxia on the expression of 11
      beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and 2 genes in preterm
      fetal sheep. METHODS: Fetal liver and kidney as well as placental tissues were
      collected at days 111-113 of gestation (term = 145 days) after 8 hours of
      sustained hypoxemia induced by lowering the maternal inspired oxygen (n = 7) or
      after 8 hours of normoxia to serve as controls (n = 5). Changes in the levels of
      11 beta-HSD1 and 11 beta-HSD2 mRNA were determined by Northern blot analysis
      using ovine 11 beta-HSD types 1 and 2 cDNAs as probes. Levels of 11 beta-HSD2
      activity were determined by a standard radiometric conversion assay. RESULTS: In
      hypoxic fetuses, there was a tendency for a decrease (P = .08) in levels of 11
      beta-HSD2 mRNA in the kidney. This decrease was correlated significantly with the
      degree of associated fetal acidemia (P < .01). However, there were no
      corresponding changes in the level of renal 11 beta-HSD2 enzyme activity,
      indicating that changes in 11 beta-HSD2 mRNA were unlikely carried through to 11
      beta-HSD2 protein. In contrast levels of 11 beta-HSD1 mRNA in the placenta and
      fetal liver were unchanged after sustained hypoxia. CONCLUSION: These results
      demonstrate that fetal hypoxemia-induced acidosis selectively down-regulates 11
      beta-HSD2 mRNA expression in the preterm fetal sheep kidney. This may provide a
      further mechanism whereby fetal acidosis alters developmental processes by
      regulating the bioavailability of glucocorticoids in specific fetal organs
      through altered local expression of 11 beta-HSD enzymes.

PMID- 9258876
TI  - A placebo-controlled, blinded comparison between betamethasone and dexamethasone
      to enhance lung maturation in the fetal mouse.
AB  - OBJECTIVE: To compare the effects of betamethasone and dexamethasone used to
      enhance lung maturity of the fetal mouse. METHODS: Adult CD-1 mice were
      administered a single dose of either a placebo or different strengths of
      betamethasone (0.01, 0.025, or 0.10 mg) or dexamethasone (0.025 or 0.10 mg) on
      day 14.0 (74%) of gestation. The eight gravid mice in each treatment cohort were
      killed on day 16.5 to assess fetal lung maturity (histologic changes and
      respiratory patterns) in a blinded manner. Another ten gravid mice in each
      treatment group were allowed to deliver spontaneously to assess perinatal
      outcomes. RESULTS: Compared with the effects from placebo exposure, the 0.10-mg
      doses of both betamethasone and dexamethasone demonstrated enhanced histologic
      maturational changes and improved neonatal respiratory efforts. Betamethasone was
      twofold to threefold more potent than dexamethasone. The fetal crown-rump lengths
      and the fetal body, lung, and heart weights were indistinguishable among the
      three treatment groups. Compared with the fetal liver weight in the placebo group
      (55.0 +/- 2.2 mg), the liver was less heavy after exposure to 0.10 mg of
      betamethasone (45.6 +/- 2.0 mg; P < .005), 0.025 mg of dexamethasone (47.6 +/-
      1.7 mg; P < .02), or 0.10 mg of dexamethasone (43.8 +/- 1.5 mg; P < .001). No
      significant differences were observed between the 0.10-mg treatments of either
      corticosteroid and placebo for the duration of gestation, litter size, survival
      rate, birth weights, or weight gains to postnatal day 26. CONCLUSION: A single
      subcutaneous dose of 0.10 mg of betamethasone was twofold to threefold more
      potent than dexamethasone in accelerating fetal lung maturity without impairing
      fetal survival or weight gain. The unexpected finding of a reduced fetal liver
      weight with either corticosteroid warrants clinical correlation.

PMID- 9258877
TI  - Antepartum and postpartum thrombomodulin levels in preeclamptic and normotensive
      pregnancies.
AB  - OBJECTIVE: To determine whether changes in plasma levels of thrombomodulin from
      antepartum to postpartum reflect the postpartum regression of preeclampsia.
      METHODS: Twenty-four preeclamptic women and 34 healthy, normotensive women with
      singleton pregnancies were studied in the third trimester. Plasma levels of
      thrombomodulin in the antepartum and postpartum periods were measured by a two
      site immunoenzymatic assay. Two-tailed Student t test and paired-comparison t
      test were used for statistical analyses. The results were expressed as mean +/-
      standard error. RESULTS: Antepartum plasma thrombomodulin levels in preeclampsia
      were significantly higher than postpartum levels (71.3 +/- 8.5 versus 55.5 +/-
      5.4 ng/mL; P = .006), which was not seen in the normotensive controls (49.9 +/-
      3.1 versus 44.2 +/- 3.8 ng/mL; P > .05). Antepartum plasma levels of
      thrombomodulin in preeclamptic women were significantly higher than those in the
      normotensive controls (P = .01). However, postpartum plasma levels of
      thrombomodulin in preeclamptic women were not significantly higher than those in
      the normotensive controls (P > .05). CONCLUSION: Significantly decreased
      postpartum plasma thrombomodulin levels in preeclamptic pregnancies strongly
      correspond to clinical postpartum regression of preeclampsia.

PMID- 9258878
TI  - Early neonatal nucleated erythrocyte counts in preterm deliveries: clinical and
      pathologic correlations.
AB  - OBJECTIVE: To determine the relation between the initial neonatal nucleated
      erythrocyte (nRBC) count and acute infection or ischemia in cases delivered
      before 32 weeks' gestation. METHODS: A set of 465 nonanomalous singleton live
      births delivered at 22-32 weeks' gestational age (GA) contained 386 cases with a
      complete blood count obtained by 3 hours of life, including 173 cases of
      premature rupture of the membranes (PROM) before labor, 143 cases of preterm
      labor with intact membranes (PTL), and 70 cases of preeclampsia. Maternal and
      neonatal charts were reviewed. Placental histopathology was scored in the
      following five categories: acute intrauterine inflammation, uteroplacental
      vascular lesions, intraplacental vaso-occlusive lesions, chronic inflammation,
      and coagulation-related lesions. The initial nRBC count (nRBCs/100 white blood
      cells [WBC] x WBC count/dL) was analyzed. RESULTS: In PROM and PTL (controlling
      for GA), the nRBC count was directly related to the maternal WBC count (PTLP =
      .018), maternal temperature within 24 hours of delivery (PROM P = .014), initial
      neonatal WBC count (PROM P < .0001; PTL P = .0004), total myeloid elements (PROM
      P = .005, PTL P = .009), total nonmyeloid elements (PROM P < .0004, PTL P <
      .0001), and total placental acute inflammatory score (PROM P = .04, PTL P = .02).
      In preeclampsia, cytotrophoblast proliferation (P = .02), villous edema (P =
      .008), "hemorrhagic endovasculitis" (P = .04), and histologic abruption (P =
      .0006) were directly related to the nRBC count. In well-grown, nonacidotic,
      nondepressed preterm infants, the nRBC count was independent of gestational age,
      with the 90th percentile at 5229 nRBC/dL. CONCLUSION: When preterm PROM and PTL
      are accompanied by acute ascending infection, nRBC release may be a fetal
      response to the inflamed environment. In preterm preeclampsia, nRBC elevation
      marks uteroplacental hypoperfusion.

PMID- 9258880
TI  - Response of the primate secretory endometrium to subchronic hypercortisolemia.
AB  - OBJECTIVE: To assess the impact of subchronic and moderate hypercortisolism on
      the secretory endometrium of the cynomolgus monkey. METHODS: Osmotic pumps
      containing hydrocortisone phosphate (HP) were implanted subcutaneously in each
      monkey on the first day of the menstrual cycle; each monkey also received pumps
      containing saline in another cycle. Blood was obtained three times per week and
      urine was collected daily for hormone analyses. Endometriectomy was performed 13
      +/- 1 days after the serum estradiol (E2) peak in each study cycle. RESULTS:
      Infusion of HP elevated serum cortisol levels by an average of 70%. Mean serum
      progesterone (P) levels were decreased by 50% during the secretory phase of HP
      treatment cycles by comparison with self-control cycles (P < .01); as a result,
      the mean endometrial glycogen concentration was reduced by 30% (P < .05) and the
      activity of 17 beta-hydroxysteroid dehydrogenase was decreased by 70% (P < .05).
      Serum E2 levels were not consistently elevated by HP treatment, but cytosolic
      estrogen receptor levels of the endometrium were decreased by 50% (P < .01),
      indicating increased estrogenic stimulation. Histologic development of the
      secretory endometrium was retarded, but the length of the secretory phase was not
      affected by the treatment. CONCLUSION: A moderate elevation of serum cortisol
      levels over one menstrual cycle consistently produced a reduction in serum P and
      a hypoprogestogenic-hyperestrogenic response of the secretory endometrium in the
      cynomolgus monkey.

PMID- 9258879
TI  - Rat ovarian insulin-like growth factor binding protein-4: a hormone-dependent
      granulosa cell-derived antigonadotropin.
AB  - OBJECTIVE: To assess the in vivo regulation of ovarian insulin-like growth factor
      binding protein-4 (IGFBP-4) mRNA expression by gonadotropins and estrogen.
      METHODS: Whole ovarian RNA, obtained from two models of follicular development,
      was extracted and analyzed by Northern blotting. Immature rats were treated with
      pregnant more serum gonadotropin (PMSG) followed 48 hours later with hCG, or
      alternatively were hypophysectomized and treated with FSH and/or
      diethylstilbestrol (DES). Localization of IGFBP-4 expression was assessed in the
      former study by in situ hybridization. Finally, the ability of human IGFBP-4 to
      antagonize FSH-stimulated progesterone accumulation was assessed in vitro.
      RESULTS: The ovarian content of IGFBP-4 transcripts increased threefold (P < .05)
      at 12 hours after PMSG but was near baseline at 24 and 48 hours. The abundance of
      IGFBP-4 mRNA increased (P < .05) again at 6 and 24 hours after hCG. The
      expression of IGFBP-4 was localized to granulosa cells of preantral (untreated)
      and small antral (12 hours after PMSG) follicles. No IGFBP-4 expression was noted
      in large (gonadotropin-primed) antral follicles. Hypophysectomy increased (P <
      .05) the ovarian content of IGFBP-4 mRNA by 1.5-fold, an effect further enhanced
      (1.8-fold; P < .05) by the provision of FSH and DES. In vitro studies revealed
      the ability of increasing concentrations (0.01-1 microgram/mL) of recombinant
      human IGFBP-4 to inhibit the FSH-supported accumulation of progesterone.
      CONCLUSION: Increased expression after administration of PMSG, hCG, and FSH/DES
      suggests that IGFBP-4 is a dynamic and hormonally responsive component of the
      ovarian cycle. The lack of expression in preovulatory follicles and its
      antigonadotropic actions in vitro imply that the attenuated expression of IGFBP-4
      may constitute a requirement for successful follicular maturation.

PMID- 9258881
TI  - Human endometrial transforming growth factor-alpha: a transmembrane, surface
      epithelial protein that transiently disappears during the midsecretory phase of
      the menstrual cycle.
AB  - OBJECTIVES: To characterize the forms of transforming growth factor-alpha (TGF
      alpha) in normal human endometrium, to evaluate the regional and temporal changes
      in TGF-alpha expression, and to correlate the pattern of TGF-alpha expression
      with physiologic events in the endometrium. METHODS: Immunohistochemistry and
      Western blot analyses were performed using two TGF-alpha antisera, one raised
      against the active extracellular N-terminus and the other recognizing the
      intracellular carboxy terminus of the protein. Immunohistochemistry was performed
      on hysterectomy specimens from premenopausal women with normal menstrual cycles.
      Soluble and membrane-bound endometrial proteins were isolated from fresh tissue
      for Western blot analysis. RESULTS: Antibodies recognizing the intracellular and
      extracellular domains of TGF-alpha exhibited identical immunohistochemical
      staining patterns. Transforming growth factor-alpha localized primarily to
      endometrial epithelial cells, and the most intense staining was in the luminal
      surface epithelium. In the surface epithelium, TGF-alpha staining was intense in
      the proliferative phase, decreased during the early secretory phase, was at its
      nadir in the midsecretory phase, and rebounded in the late secretory phase.
      Western blot analysis demonstrated two transmembrane forms. The 28-kD protein
      contained both intracellular and extracellular antigens, and the 18-kD protein
      contained only the intracellular antigen. CONCLUSION: Western blot data were
      consistent with the hypothesis that the extracellular segment of TGF-alpha is
      cleaved from the transmembrane precursor in vivo, as has been demonstrated in
      other tissues. Immunohistochemistry demonstrated that the TGF-alpha antigens are
      concentrated in the luminal surface epithelium and decline and disappear in the
      early to midsecretory phase. These findings suggest that the most active period
      of membrane-bound TGF-alpha cleavage corresponds with the interval during which
      preimplantation embryos are in the uterine cavity.

PMID- 9258882
TI  - Succinylcholine-induced "masseter spasm".

PMID- 9258883
TI  - Mivacurium in an obese patient with myotonic dystrophy--a case report.
AB  - Mivacurium is a short-acting non-deplolarizing neuromuscular blocking agent. Its
      use in an obese patient with myotonic dystrophy undergoing laparoscopic
      cholecystectomy is reported. Mivacurium was used as a bolus dose of 0.07 mg. kg
      1, followed by a continuous infusion at the rate of 0.003 mg. kg-1. min-1. Muscle
      relaxation, monitored by a train of four count, was adequate throughout the
      surgery. Spontaneous recovery of the neuromuscular function was obtained fifteen
      minutes after the end of mivacurium infusion. Neostigmine was not given.
      Postoperative mechanical ventilation and respiratory complications were avoided.

PMID- 9258884
TI  - Ipsilateral bronchial intubation in a neonate for expansion of post-operative
      unilateral atelectasis--case report.
AB  - Ipsilateral bronchial intubation was used for reexpansion of unilateral pulmonary
      atelectasis in a newborn, who developed postoperative right atelectasis following
      extrapleural repair of tracheoesophageal fistula.

PMID- 9258885
TI  - The anesthetic management of a patient with pemphigus vulgaris--a case report.
AB  - The anesthetic management of a patient with pemphigus vulgaris who required
      general anesthesia and endotracheal intubation for craniotomy operation is
      described. The anesthesia was assured with Diprivan. Vecuronium
      bromide/isoflurane/nitrous oxide in oxygen and fentanyl when necessary. No
      anesthetic and surgical complication occurred.

PMID- 9258886
TI  - The anterior approach to sympathetic ganglion block.

PMID- 9258887
TI  - Brain-stem auditory evoked potentials comparison between 1.3 and 1.5 MAC of
      isoflurane-nitrous oxide anesthesia.

PMID- 9258888
TI  - Preanesthetic wrapping of legs for prevention of spinal induced hypotension.
AB  - Forty-four male patients undergoing herniorrhaphy under spinal anesthesia were
      allocated to 2 groups. Group I had 15 ml/kg of lactated ringer intravenously as
      prehydartion for prevention of spinal induced hypotension. Group 11 had the
      trendelenbourg position to 30 degrees for 2 minutes and the legs wrapped with
      elastic Esmarch bandage prior to spinal anesthesia without fluid prehydration. In
      both groups, ephedrine was used to treat spinal induced hypotension. The later
      was defined as a decrease in the systolic arterial pressure less than 75% of the
      baseline value. The incidence of hypotension was greater in the fluid
      prehydration group (4 of 22) as well as the mean dose of ephedrine required to
      treat hypotension (7 +/- 10 mg) than the group with wrapping of the legs (1 of 22
      and 5 +/- 0 mg). It is concluded that trendelenbourg position and wrapping of the
      legs prior to the spinal block might prevent the sudden decrease in arterial
      blood pressure that occurs during spinal anesthesia.

PMID- 9258889
TI  - Specific hippocampal volume reductions in individuals at risk for Alzheimer's
      disease.
AB  - Our goal was to ascertain the involvement of the temporal lobe in the preclinical
      (not yet diagnosable) stages of dementia of the Alzheimer's type (DAT) by using
      MRI-derived volumes. We assessed anatomical subdivisions of the temporal lobe on
      three groups of carefully screened age- and education-matched elderly
      individuals: 27 normal elderly (NL), 22 individuals with minimal cognitive
      impairment (MCI), who did not fulfill DAT criteria but were regarded at high risk
      for future DAT, and 27 DAT individuals. We found hippocampal volume reductions of
      14% for the MCI and 22% for the DAT group compared to the NL group. Utilizing
      regression analyses and after accounting for gender head size-age, generalized
      atrophy (CSF), and other temporal lobe subvolumes, the hippocampal volume
      separated NL from MCI individuals, correctly classifying 74%. For NL and MCI
      groups combined the hippocampal volume was the only temporal lobe subvolume
      related to delayed recall memory performance. When contrasting MCI and DAT
      individuals, the fusiform gyrus volume uniquely improved the ability of the
      hippocampal volume to separate MCI from DAT individuals from 74 to 80%. Our cross
      sectional data suggest that, within the temporal lobe, specific hippocampal
      volume reductions separated the group at risk for DAT from the normal group. By
      the time impairments are sufficient to allow a diagnosis of DAT to be made, in
      addition to the medial temporal lobe volume reductions, the lateral temporal lobe
      is also showing volume reductions, most saliently involving the fusiform gyrus.

PMID- 9258890
TI  - beta-Amyloid (A beta) deposition in the brains of aged orangutans.
AB  - While aged monkeys of several species show cerebral amyloid deposition in senile
      plaques and blood vessels similar to that seen in human aging and Alzheimer's
      disease (AD), studies of great apes have been limited. Using histological and
      immunohistochemical methods, we examined the brains of four orangutans aged 10,
      28, 31, and 36 years. We encountered sparse beta-amyloid (A beta)-immunoreactive,
      silver-negative plaque-like structures in the brains of the three older apes. The
      36-year-old orangutan also evidenced small A beta-positive deposits in
      subcortical white matter and sparse vascular amyloid deposition, primarily in
      meningeal vessels. Neurofibrillary tangles were not detected on silver stains or
      on tau or ubiquitin immunohistochemistry. Many of the A beta-positive plaque-like
      deposits in the orangutans were apolipoprotein E-immunoreactive, as we have
      previously reported in aged rhesus monkeys and an aged chimpanzee. Also,
      paralleling our earlier findings in these nonhuman primates, A beta 40 in plaques
      was more prominent in the orangutan than is typically seen in human aging, AD,
      and Down syndrome. These intriguing species differences may provide clues to the
      mechanisms of amyloid deposition and the development of neuropathologic changes
      in AD.

PMID- 9258891
TI  - Activated Alzheimer disease platelets retain more beta amyloid precursor protein.
AB  - Upon activation, platelet alpha-granules' soluble contents are secreted and
      membrane-bound contents are translocated to the plasma membrane. Membrane-bound
      proteins include the beta-amyloid precursor protein (APP) from which the beta
      amyloid (A beta) deposits found surrounding the cerebrovasculature of patients
      with Alzheimer's Disease (AD) may originate. We show here that activated
      platelets from AD patients exhibit less APP processing, retain more of the
      protein on their surface, and secrete less as soluble fragments than do controls.
      Surface labeling demonstrated that there is little APP or CD62 on the surface of
      resting platelets. Upon activation, control platelets exhibited more of both
      proteins on their surface, while advanced AD patients exhibited similar amounts
      of CD62 as controls, but retained significantly more surface APP. AD platelets
      secreted similar amounts of most soluble alpha-granule contents as controls, but
      less APP fragments. Together these results suggest a processing defect that may
      account for greater deposition of A beta-containing products in the vasculature
      to which activated platelets adhere.

PMID- 9258893
TI  - Olfactory identification in elderly schizophrenia and Alzheimer's disease.
AB  - In the present study we assessed olfactory identification ability using the
      University of Pennsylvania Smell Identification Test (UPSIT) in 16 elderly
      patients with schizophrenia (ES), 20 patients with a diagnosis of probable
      Alzheimer's disease (AD), and 20 healthy elderly controls (EC). Both patient
      groups exhibited marked deficits in UPSIT performance relative to controls. ES
      and AD patients with similar levels of general cognitive impairment did not
      differ on the UPSIT, suggesting that the two disorders may share a common
      dysfunction in olfactory brain regions. While there have been recent reports of
      greater olfactory impairment in males, neither patient group exhibited
      significant gender differences on the UPSIT.

PMID- 9258892
TI  - Moderate and advanced Alzheimer's patients exhibit platelet activation
      differences.
AB  - We previously reported that platelets from advanced sporadic Alzheimer's disease
      (AD) patients exhibit two defects: first, an aberrant signal transduction
      presenting as a thrombin-induced hyperacidification, which is more severe for
      donors with the apolipoprotein E4 allele (apoE4), and second, an AD-specific
      Amyloid Precursor Protein (APP) processing defect that presents as retention of
      APP on the activated platelets' surface and in independent of the apo E allele.
      This retention of membrane APP correlates with decreased release of soluble APP.
      To determine at what stage in the disease progression these defects appear, we
      performed signal transduction and secretion studies on moderate AD patients.
      Thrombin-activated platelets from these patients do not exhibit either
      hyperacidification or APP retention; their APP processing and secretion are
      normal by Western blotting, suggesting that the two platelet defects appear in
      the advanced stages of AD.

PMID- 9258894
TI  - Automatic and effortful processing in aging and dementia: event-related brain
      potentials.
AB  - Automatic and effortful processes were investigated using event-related brain
      potentials (ERPs) recorded from moderately impaired subjects with probable
      Alzheimer's Disease (AD), normal elderly, and normal young controls. The effects
      of effortful attention on ERPs to loud noises and the effects of stimulus
      intrusiveness on effortfully elicited ERPs were studied. First, ERPs to task
      relevant and irrelevant startling noises were compared. Second, ERPs to startling
      noises and moderate tones were compared when both were targets. The effects of
      age (young vs. elderly controls) and effects of dementing disease (AD subjects
      vs. elderly controls) were also assessed. Effortful attention augmented noise
      elicited P300 amplitude in elderly subjects, but not in young. Intrusiveness
      augmented task-relevant P300 amplitude in young subjects, but not in elderly.
      Neither variable affected P300 amplitude in AD subjects. Thus, effects of age and
      disease depended on how P300 was elicited: when effortfully elicited, P300
      amplitude was affected by disease but not age; when automatically elicited, P300
      amplitude was affected by age but not disease. N1 effects differed from P300
      effects.

PMID- 9258896
TI  - Sex differences in the corpus callosum with aging.
AB  - The present study examined sex differences in the area and age-related atrophy of
      the corpus callosum (CC) of 76 healthy elderly subjects using magnetic resonance
      imaging. The cerebellum and pons served as noncortical control structures. CC
      area and its subregions were also related to cognitive performance. Women had a
      slightly larger posterior sector of the CC than men. Women but not men showed age
      related atrophy of the anterior and middle sectors of the CC but not the
      posterior sector. Cerebellum and pons size was similar in men and women, and
      neither showed age-related atrophy. CC area was related to visual memory in women
      but not men; no other significant cognitive to structure area relationships were
      found. These findings show that selective age related atrophy of the CC differs
      in men and women late in life.

PMID- 9258895
TI  - Distinct processing of endogenous and overexpressed recombinant presenilin 1.
AB  - The presenilin 1 (PS1) gene has been identified by positional cloning. More than
      30 mutations were detected in this gene which cosegregate with Alzheimer's
      disease (AD). Understanding their role in disease pathogenesis requires a
      characterization of the PS1 protein. We have generated a set of antibodies
      against the three major hydrophilic domains of the deduced amino acid sequence.
      Analyzing cultured cells and brain samples, we identified the endogenous PS1
      polypeptide as well as amino- and carboxy-terminal fragments. These metabolites
      were much more abundant than the full-length molecule, indicating substantial
      processing. Overexpression of human PS1 markedly increased the full-length
      polypeptide but hardly altered the amount of the metabolites. Instead, additional
      proteolytic fragments appeared suggesting a different metabolism of the excess
      PS1, which may impede studies in transfected cells. Our results indicate a tight
      regulation of the endogenous PS1 metabolites. PS1 and its fragments are shown to
      be integral membrane proteins of the endoplasmic reticulum. The mechanisms
      regulating the generation of the metabolites, their potential function, and role
      in AD remain to be studied.

PMID- 9258897
TI  - A stereological study on the nuclear volume of cerebellar granule cells in aging
      rats.
AB  - A morphometric study on age changes of rat cerebellar cortex (Crus I and Crus II)
      was carried out. The nuclear volume of the granule cells was estimated by means
      of two unbiased stereological methods: the nucleator, which enabled the
      estimation of the number-weighted mean volume (VN), and the point-sampled
      intercepts method, allowing the determination of the volume-weighted mean volume
      (VV). These parameters enabled the estimation of the coefficient of variation of
      nuclear volume in the number-weighted distribution [CV(VN)]. All parameters were
      determined in eight age groups (2, 6, 9, 12, 15, 18, 21, and 24 months--five
      animals per age) and the mean values of each age group were compared using one
      way ANOVA with post hoc comparisons, and regression analysis. It was demonstrated
      for the first time, using unbiased techniques, that the nucleus of granule cells
      of the cerebellar cortex showed a significant decrease in its mean volumes (VV)
      with age, especially from 21 months onwards. Although CV(VN) was not correlated
      with age, it was also demonstrated that these cells bear a considerable nuclear
      size pleomorphy that was maintained throughout the age spectrum.

PMID- 9258898
TI  - Chronic treatment of Syrian hamsters with low-dose selegiline increases life span
      in females but not males.
AB  - The only intervention conclusively shown to prolong life span in mammals is
      caloric restriction. Selegiline, a selective, irreversible inhibitor of monoamine
      oxidase B (MAO-B), is the first drug reported to reproducibly increase mean and
      maximum life span in animals, although this has only been demonstrated in male
      rats and mice. The effect on life span is commonly assumed to depend on MAO-B
      inhibition, but final experimental proof is missing. Therefore, we investigated
      the possible relationship between selegiline's effect on life span and MAO-B by
      monitoring survival data and MAO activity in Syrian hamsters of both sexes.
      Selegiline (0.05 mg/kg) significantly increased life span in female Syrian
      hamsters, but not in males. In contrast, MAO-B was inhibited equally in both
      sexes by about 40%, although females had a higher baseline MAO-B activity. No
      increase in MAO-B with age was observed. Female control hamsters had a shorter
      life span than male controls. Interestingly, this sex difference disappeared in
      the selegiline-treated animals. These findings suggest that the increase of life
      span by selegiline might be independent of MAO-B inhibition, but is possibly
      related to mechanisms determining sex differences of life span.

PMID- 9258899
TI  - Amelioration of age-related deficits in the stimulation of synapsin
      phosphorylation.
AB  - In a previous report we demonstrated that aged (24-26 month) rats have deficits
      in long-term potentiation, a form of synaptic enhancement that is dependent on
      protein phosphorylation (Moore et al., Hippocampus, 3:57-66; 1993). In the
      present study we demonstrate that aged rats have a deficit in the phosphorylation
      of the synaptic vesicle associated protein synapsin I. Specifically, aged animals
      exhibit defective phorbol ester-induced stimulation of synapsin phosphorylation
      at its calcium/calmodulin dependent protein kinase II sites. We also examined the
      effects of caloric restriction and antioxidant therapy on this age-related
      deficit. We found that either life-long caloric restriction or treatment with 16
      mg/kg N-tert-butyl-alpha-phenylnitrone (PBN) for 2 weeks can at least partially
      ameliorate the age-related deficit in the phorbol ester stimulation of synapsin
      phosphorylation.

PMID- 9258900
TI  - Motor function in young and aged hemiplegic rats: effects of a Ginkgo biloba
      extract.
AB  - We have previously shown beneficial effects of a Ginkgo biloba extract (EGb761
      IPSEN) in accelerating functional recovery from hemiplegia induced by unilateral
      motor cortex ablation. Here, we report the behavioral and histological effects of
      various dose regimes of EGb761. In young rats (3 months), 10 mg/kg/day for 7 days
      produced an improvement in motor performance, relative to untreated controls, on
      the last day of treatment. Applying a priming (P)-maintenance (M) dose regime (P
      7 = 7 days, M-21 = 21 days), a P-7 of 50 (all doses expressed in mg/kg/day) and a
      M-21 of 10 promoted recovery from the second day after surgery. However, in aged
      rats (26-28 months old) this treatment ameliorated motor performance only after
      the 10th day of treatment. A P-7 of 100 or 200 and a M-21 of 50 or 100 produced
      an acceleration of behavioral recovery in aged animals. Improvement was evident
      by the fifth day of treatment and was maintained after the treatment regimen.
      These two groups also demonstrated reduced glial fibrillary acid protein (GFAP)
      immunostaining and ex vacuo hydrocephalus. Thus, the confirmed efficacy of EGb in
      hemiplegic rats can be enhanced by an appropriate posology.

PMID- 9258901
TI  - Intracellular calcium buffering declines in aging adrenergic nerves.
AB  - Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves
      increased with advancing age in the Fischer-344 rat when function of
      norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were
      blocked. When calcium channels were bypassed with the ionophore, ionomycin (4
      microM), norepinephrine release from aged nerves (20 months) was still elevated
      as compared to 6-month-old nerves. Norepinephrine release stimulated by high K+
      was also higher in 20-month nerves. The intracellular calcium chelator, 1,2 bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetomethylester (BAPTA/AM), was used to
      determine whether age-related increases in norepinephrine release could be
      reversed with the addition of an artificial intracellular calcium buffer.
      Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both
      old and young tail arteries; however, the effect was significantly greater in
      older arteries. When mitochondrial calcium uptake was compromised using the
      uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused
      a further decrease in stimulation-evoked norepinephrine release in 20-month tail
      arteries with much less effect in 6-month-old nerves. These results suggest that
      intracellular calcium buffering is less efficient in older nerves.

PMID- 9258902
TI  - Nigrostriatal monoamine oxidase A and B in aging squirrel monkeys and C57BL/6
      mice.
AB  - In this study we assessed the two forms of monoamine oxidase (MAO) in the
      caudate, putamen, and substantia nigra of young (4-year-old), intermediate-aged
      (11-year-old), and aged (20-year-old) squirrel monkeys and in the striata of
      young (2-month-old) and older (10-month-old) C57Bl/6 mice. MAO A and B activities
      were determined by measuring the rate of oxidation of the specific substrates
      phenethylamine and serotonin. In squirrel monkey, the vast majority of MAO
      activity was MAO B with activity of this isoform 10 times greater than of MAO A,
      while in mice the activity of the two forms was approximately equivalent.
      Although mice demonstrated nearly twofold selective increases in striatal MAO B
      between 2 and 10 months of age, neither MAO B nor A showed statistically
      significant changes with age in squirrel monkeys. These results document the
      marked differences between nonhuman primates and rodents with respect to the
      relative activities and the effects of age on MAO A and B, and indicate that
      increased MAO is not an inevitable feature of aging.

PMID- 9258903
TI  - In vivo amino acid release from the striatum of aging rats: adenosine modulation.
AB  - The release of glutamate, aspartate, GABA, and taurine from the striatum of young
      (3 months), mature (12 months), and old (22 months), freely moving male rats was
      investigated by using a microdialysis fiber inserted transversally in the
      striatum. In old rats basal extracellular glutamate and aspartate levels were
      decreased vs. young rats (-38 and -49%, respectively). GABA and taurine levels
      were unmodified by age. In the presence of the adenosine receptor antagonist 8
      phenyltheophilline (8-pT) at the concentration of 50 microM, both K(+)-evoked
      releases of glutamate and aspartate were more than doubled in young, but not in
      mature and old rats. 8-pT at the concentration of 500 microM significantly
      decreased glutamate basal levels and K(+)-evoked aspartate release in old rats
      only. GABA and taurine releases were not affected by 8-pT at either dose. Our
      findings indicate a modified adenosine modulation on glutamate and aspartate
      release in aged rats, that could result from a change in the balance between A1
      and A2a adenosine receptor density or an alteration of A1 and A2a receptor
      effector coupling.

PMID- 9258904
TI  - The effect of aging on rat striatal D1 receptor mRNA-containing neurons.
AB  - In situ hybridization of a digoxigenin-labeled oligonucleotide probe combined
      with computer assisted image assessment was used to directly visualize D1
      dopamine receptor mRNA-containing neurons in rat striata, and quantify age
      related changes in the sizes and relative mRNA content of these neurons. It was
      found that 1) numbers of D1 mRNA-containing neurons appear to decrease in striata
      of aged rats; 2) relative amounts of D1 receptor mRNA in individual striatal
      neurons do not change during aging; and 3) neurons of all sizes appear to be
      lost, with the greatest absolute decrease in those larger than 150 microns2.
      These data confirm the age associated loss of D1 dopamine receptors reported for
      some other rat strains in that species, and further suggest that neuronal loss is
      responsible for the decrement. The latter finding contrasts with the aging
      associated loss of D2 dopamine receptors, which additionally involves decreased
      amounts of mRNA per cell.

PMID- 9258905
TI  - Histamine H2 blocking drugs and the risk for Alzheimer's disease: the Rotterdam
      Study.
AB  - We investigated the cross-sectional relation of the use of histamine H2 blocking
      drugs and the risk for AD in the population based Rotterdam Study. AD was
      clinically diagnosed according to DSM-IIIR and NINCDS-ADRDA criteria. Data on
      medication used in the past week were obtained by having subjects show vials of
      medications and were classified according to the Anatomical Therapeutic Chemical
      (ATC) index. There were 7276 subjects with complete data, including 208 with AD
      and 378 H2 users (ATC code A0BA). Compared to the total cohort of non-H2 users,
      the relative risk (estimated as the odds ratio) for AD among those taking H2
      blockers was 0.95 (95% confidence interval (CI) 0.52-1.75), after controlling for
      age, education, sex, history of stroke, and use of benzodiazepines and
      nonsteroidal antiinflammatory drugs. To address unmeasured confounding (by
      (contra) indication), we compared the risk of AD in H2 users with a subset of
      subjects using topical medications (ATC code D and S; n = 436). The adjusted OR
      in this comparison was 1.24 (95% CI 0.52-2.98). These results do not support the
      hypothesis that use of histamine H2 blocking drugs protect against AD.

PMID- 9258906
TI  - Free Ca2+ levels and expression of biochemical markers in Alzheimer's
      fibroblasts.

PMID- 9258907
TI  - Neural precursor cells: applications for the study and repair of the central
      nervous system.
AB  - A combination of gene transfer and intracerebral transplantation techniques has
      been used in studies of CNS development to provide the most compelling evidence
      to date that the broad diversity of cell types that exist in the CNS arises from
      single precursor cells. Although the factors that influence cellular
      differentiation in vivo remain to be clarified, work conducted in vitro with
      neural precursors has demonstrated that environmental signals (both soluble
      factors and substrate molecules) play a pivotal role in these decisions. In
      particular, FGF-2 appears to be one of the prominent influential factors involved
      in CNS development (see Temple & Qian, 1995). The generation of immortalized
      precursor populations that are capable of differentiating into multiple CNS cell
      types in vivo has significant implications for the treatment of neural
      dysfunction. Such cells may be manipulated toward a lineage that synthesizes
      factors of interest and used in grafting strategies to replace substances that
      are lost after injury or in neurodegenerative disease. Alternatively, precursor
      cells may be directed to a neuronal lineage and used to functionally repair
      damaged neural systems. Finally, genetic modification of precursor populations
      provides a method for introducing therapeutic gene products both into discrete
      regions of the brain and into widely dispersed areas of the CNS. In considering
      applications to human disease, it has been reported that nestin is expressed in
      human neuroepithelial cells (Tohyama et al., 1992), suggesting the existence of
      neural precursors. Recently, such precursors were in fact isolated by two
      separate groups (Kirschenbaum et al., 1994; Sabate et al., 1995) and shown to be
      amenable to gene transfer and to successfully survive transplantation into the
      brain of experimental animals (Sabate et al., 1995). Such findings encourage the
      possibility that precursor cells from the human CNS may be utilized in cell
      replacement or gene therapy strategies directed toward human neurodegenerative
      disorders. While immortalization techniques have been essential for generating
      large quantities of precursor cells for study and transplantation, the genetic
      modification of cells may alter vital cellular properties. Thus, the ability to
      induce the proliferation of nonimmortalized neural populations in vitro with the
      use of growth factors (see section on CNS precursor cells above) provides an
      important alternative approach for developing perpetual neural cell lines. Recent
      work with such growth factor-responsive precursor cells has suggested their
      therapeutic potential in the CNS, as evidenced by the finding that FGF-2
      responsive cells can successfully engraft and express transgenes in the adult
      brain (Gage et al., 1995; Sabate et al., 1995; Suhonen et al., 1996). Continuing
      studies with these cells will provide additional insight into the properties of
      primary CNS stem cells and increase the range of precursor populations that are
      useful for exploring the development, function, and plasticity of the CNS.

PMID- 9258908
TI  - Can blood-brain barrier play a role in the development of cerebral amyloidosis
      and Alzheimer's disease pathology.

PMID- 9258909
TI  - Permeability and residual plasma volume of human, Dutch variant, and rat amyloid
      beta-protein 1-40 at the blood-brain barrier.
AB  - The permeability of normal human, the human Dutch variant, and the rat A beta 1
      40 proteins at the blood-brain barrier (BBB) was determined in the normal adult
      rat by quantifying the permeability coefficient-surface area (PS) product for
      each protein after correction for the residual plasma volume (Vp) occupied by the
      protein in the blood vessels of different brain regions. The PS for normal and
      Dutch A beta ranged from 13 x 10(-6) to 22 x 10(-6) ml/g/s in different brain
      regions, which is 130 to 220 times greater than albumin. These high PS values
      compare to that of insulin, whose uptake is decidedly by a receptor-mediated
      transport process, and suggest a similar mechanism for A beta. Remarkably, the PS
      for rat A beta was 4 times higher and ranged from 54 x 10(-6) to 82 x 10(-6)
      ml/g/s for different brain regions, suggesting a distinctive species specificity.
      While the Vp values of human and rat A beta were comparable, the Dutch variant
      was 2 to 3 times higher, indicating adherence to the vessel walls in different
      brain regions, consistent with the heavy A beta deposition that has been
      described in intracerebral vessel walls with this variant. The high PS values
      observed for A beta at the BBB suggest that sources outside the nervous system
      could contribute, at least in part, to the cerebral A beta deposits seen in
      Alzheimer's disease. SDS-PAGE of 125I-labeled human A beta after 60 min of uptake
      revealed intact protein in plasma and in different brain regions. In addition,
      125I-labeled human A beta binding to a protein of 67,000 in both plasma and brain
      tissue regions was observed with SDS-PAGE. This protein was tentatively
      identified as albumin, and it was not detectable in the brain regions of animals
      that had undergone intracardiac perfusion; hence, a portion of A beta binds
      tightly to and is likely transported by albumin in plasma. The absence of this A
      beta-albumin complex in brain regions after perfusion and the low permeability of
      albumin at the BBB imply that A beta itself is efficiently transported at the BBB
      to account for the high PS values, although presentation of A beta to the
      capillary endothelial cell by albumin or other plasma proteins cannot be
      excluded.

PMID- 9258910
TI  - Cellular distribution of NMDA glutamate receptor subunit mRNAs in the human
      cerebellum.
AB  - We have used a quantitative in situ hybridization method with human
      ribonucleotide probes to examine the regional and cellular distribution of N
      methyl-D-aspartate receptor (NMDAR) subunit mRNAs in the human cerebellum.
      Purkinje cells showed very dense labeling for NMDAR1 mRNA, dense labeling for
      NMDAR2A mRNA, and moderate labeling for NMDAR2D mRNA, whereas labeling for
      NMDAR2C mRNA was low. Granule cells showed high hybridization signals for the
      NMDAR1 and NMDAR2C mRNAs and moderate signals for the NMDAR2A and NMDAR2D mRNAs.
      In addition intense labeling with the NMDAR2B probe was observed in medium-sized
      neurons with chromophilic cell bodies in the upper part of the granule cell
      layer, most likely representing Golgi cells. Neurons in the molecular layer,
      i.e., basket cells and stellate cells, showed moderate hybridization signals for
      NMDAR1 and NMDAR2D and low signal for NMDAR2C. Each type of cerebellar neuron
      analyzed displayed a distinct NMDAR2 subunit profile, suggesting that they are
      likely to have NMDA receptors with distinct properties.

PMID- 9258911
TI  - A neurotoxic and gliotrophic fragment of the prion protein increases plasma
      membrane microviscosity.
AB  - Prion-related encephalopathies are characterized by astrogliosis and nerve cell
      degeneration and loss. These lesions might be the consequence of an interaction
      between the abnormal isoform of the cellular prion protein that accumulates in
      nervous tissue and the plasma membranes. Previously we found that a synthetic
      peptide, homologous to residues 106-126 of the human prion protein, is
      fibrillogenic and toxic to neurons and trophic to astrocytes in vitro. This study
      dealt with the ability of the peptide to interact with membranes. Accordingly, we
      compared PrP 106-126 with different synthetic PrP peptides (PrP 89-106, PrP 127
      147, a peptide with a scrambled sequences of 106-126, and PrP 106-126 amidated at
      the C-terminus) as to the ability to increase the microviscosity of artificial
      and natural membranes. The first three had no effect on nerve and glial cells in
      vitro, whereas the amidated peptide caused neuronal death. Using a fluorescent
      probe that becomes incorporated into the hydrocarbon core of the lipid bilayer
      and records the lipid fluidity, we found PrP 106-126 able to increase
      significantly the membrane microviscosity of liposomes and of all cell lines
      investigated. This phenomenon was associated with the distribution of the peptide
      over the cell surface, but not with changes in the membrane lipid or protein
      content, or with membrane lipid phase transitions. Accordingly, we deduced that
      increased membrane microviscosity was unrelated to changes in the membrane native
      components and was the result of increased lipid density following PrP 106-126
      embedding into the lipid bilayer. No control peptides had comparable effects on
      the membrane microviscosity, except PrP 106-126 amidated at the C-terminus. Since
      the latter was as neurotoxic, but not as fibrillogenic, as PrP 106-126, we argued
      that the ability of PrP 106-126 to increase membrane microviscosity was unrelated
      to the propensity of the peptide to raise fibrils. Rather, it could be connected
      with the primary structure of PrP 106-126, characterized by two opposing regions,
      one hydrophilic and the other hydrophobic, that enabled the peptide to interact
      with the lipid bilayer. Based on these findings, we speculated that the glial and
      nerve cell involvement occurring in prion-related encephalopathies might be
      caused by the interaction with the plasma membrane of a PrP 106-126-like fragment
      or of the sequence spanning residues 106-126 of the abnormal isoform of the prion
      protein.

PMID- 9258912
TI  - Apolipoprotein E uptake and low-density lipoprotein receptor-related protein
      expression by the NTera2/D1 cell line: a cell culture model of relevance for late
      onset Alzheimer's disease.
AB  - Apolipoprotein E has been shown to be a risk factor for late-onset Alzheimer's
      disease, with the apolipoprotein epsilon 4 allele conferring the risk.
      Apolipoprotein E is found in neurofibrillary tangles and senile plaques, the
      pathological characteristics of Alzheimer's disease. To date there is no direct
      evidence that human neurons can take up exogenous apolipoprotein E, which is
      necessary if apolipoprotein E is involved in the formation of neurofibrillary
      tangles. To examine apolipoprotein E uptake we employed the human NTera2/D1 cell
      line, which can be induced by retinoic acid to differentiate into postmitotic
      NTera2-N neurons, which have the characteristics and morphology of human central
      nervous system neurons. We defined the cell line as genotype apolipoprotein
      epsilon 3/3 and demonstrated that the cells do not synthesize apolipoprotein E
      but can take up and internalize exogenous recombinant apolipoprotein E3. We also
      confirmed the expression of the low-density lipoprotein receptor-related protein,
      a known receptor for apolipoprotein E. The NTera2/D1 cell line therefore provides
      a useful human cell model for examining the effects of other apolipoprotein E
      isoforms with a view to defining intraneuronal interactions of apolipoprotein E.

PMID- 9258913
TI  - Gene expression of hypothalamic somatostatin and growth hormone-releasing hormone
      in dexamethasone-treated rats.
AB  - Supraphysiological doses of glucocorticoids inhibit growth hormone (GH) secretion
      in man and experimental animals. We investigated whether glucocorticoids inhibit
      GH secretion through changes in the gene expression of GH, hypothalamic
      somatostatin (SS) and GH-releasing hormone (GHRH), and whether such changes vary
      with the dose and duration of glucocorticoid excess. Male rats, 6 weeks of age,
      were treated with injections of either saline or different doses of dexamethasone
      (40, 200, 500 or 1,000 micrograms/kg/day) intraperitoneally for 3 or 8 days.
      Total RNA extracted from the anterior pituitary and hypothalamus was analyzed by
      Northern blot hybridization. SS mRNA level was also assessed in smaller
      hypothalamic fragments containing predominantly the periventricular and
      paraventricular nuclei, and by in situ hybridization. A biphasic effect on SS
      mRNA levels was observed such that a significant increase (p < 0.001) was
      demonstrated in the periventricular nucleus after 3 days of dexamethasone 1,000
      micrograms/kg/day, but a reduction in hypothalamic SS mRNA was seen after 8 days
      for all doses employed (p < 0.05 or p < 0.01). On the other hand, hypothalamic
      GHRH mRNA levels showed a reduction which appeared to increase with the dose and
      duration of treatment and became statistically significant after 8 days at doses
      > or = 200 micrograms/kg/day (p < 0.05). Pituitary GH mRNA levels were increased
      after 3 days at doses > or = 500 micrograms/kg/day (p < 0.05) but showed no
      significant change at all doses after 8 days. We conclude that glucocorticoid
      excess is associated with changes in the gene expression of GH, hypothalamic SS
      and GHRH, which vary with the dose and duration of glucocorticoid treatment.
      Glucocorticoids inhibit GH secretion in vivo through a reduction in hypothalamic
      GHRH gene expression and, in animals with shorter duration of glucocorticoid
      excess also through an increase in SS gene expression in the periventricular
      nucleus.

PMID- 9258914
TI  - Antiserum to growth hormone decreases sleep in the rat.
AB  - To determine whether an acute withdrawal of growth hormone (GH) alters sleep, the
      effects of antiserum to GH (GH-AS) on sleep were studied in the rat. Sleep-wake
      activity and cortical brain temperature (Tc) were recorded for 2 days after
      systemic injection of physiological saline. Then, one group of rats (n = 6)
      received GH-AS whereas another group of rats was injected with normal rabbit
      serum (n = 6). The injections were given 1 h before light onset, and the rats'
      behaviors were recorded for 23 h during the subsequent 12-hour light and 12-hour
      dark period. Sleep and Tc were not altered after normal rabbit serum. The
      durations of both rapid eye movement sleep (REMS) and non-REMS (NREMS), and the
      EEG slow-wave activity during NREMS were significantly suppressed during the
      light period following the injection of GH-AS. Tc tended to decrease for 3 h and
      a small rise was observed thereafter during the light period, but these changes
      were not statistically significant. The assay of GH in plasma samples obtained at
      30-min intervals for 5 h after injection of normal rabbit serum or GH-AS verified
      the decreases in plasma GH concentrations in response to GH-AS. It is suggested
      that GH may promote sleep possibly via some metabolic actions.

PMID- 9258915
TI  - Expression of insulin-like growth factor binding protein-2 during postnatal
      development of the rat neurointermediate pituitary.
AB  - The expression of insulin-like growth factor binding protein-2 (IGFBP-2) during
      postnatal development of the rat neurointermediate pituitary was characterized
      using immunocytochemistry and in situ hybridization. Glial cells in the neural
      lobe (NL) showed robust expression of IGFBP-2 throughout the postnatal period and
      continuing into adulthood. These were identified as pituicytes by the presence of
      S-100 protein; IGFBP-2 was not present in microglia in the NL. IGFBP-2
      immunoreactivity was more punctate in mature pituicytes, suggesting a possible
      association with the cell membrane. No expression of IGFBP-2 by brain astrocytes
      was observed at any age examined, even in regions such as the median eminence and
      subfornical organ that lack a blood-brain barrier. IGFBP-2 was also localized
      immunocytochemically in melanotropes and glial-like cells of the intermediate
      lobe (IL). Positive cells were most numerous in neonates and declined thereafter,
      with immunoreactivity undetectable by 65 days of age. IGFBP-2 mRNA was detected
      in the IL only at 1 day of age. These findings are consistent with a potential
      role for IGFBP-2 in modulating effects of the insulin-like growth factors during
      development of the neurointermediate lobe. The constitutive expression of high
      levels of IGFBP-2 by mature pituicytes also suggests that this protein could be
      secreted and/or influence a variety of processes in the mature NL, such as glial
      proliferation, axonal growth, or morphological plasticity of pituicytes.

PMID- 9258916
TI  - Convergence of substance P and estrogen receptor immunoreactivity in the midbrain
      central gray of female guinea pigs.
AB  - Substance P (SP) and estrogen receptor immunoreactivity overlap in the midbrain
      central gray (MCG) of female guinea pigs. Estrogen-receptor-containing cells are
      found throughout the rostrocaudal extent of the MCG. Moderately dense SP
      immunostaining is also found in this region. SP-immunoreactive punctate
      structures suggestive of boutons were found in close association with the
      processes of some estrogen-receptor-immunoreactive neurons. These associations
      were observed primarily in the lateral and ventrolateral MCG at the midcollicular
      and caudal levels. This findings suggests an anatomical substrate for
      interactions between SP and estradiol-sensitive neurons in the midbrain. Such
      interactions may underlie the effects of SP on female sexual behavior.

PMID- 9258917
TI  - Relaxin-induced expression of Fos in the forebrain of the late pregnant rat.
AB  - Relaxin, administered parenterally, has been shown to increase the release of
      oxytocin (OT) into the circulation and increase the firing rate of OTergic
      neurons. The objective of the present study was to determine if relaxin
      administration can result in the expression of a transcription factor, suggesting
      that it alters transcriptional activity within OTergic neurons at the level of
      the hypothalamus. Primigravid rats were ovariectomized and a jugular cannula was
      inserted on day 11 of gestation (g11). Pregnancy was maintained by implanting 17
      beta-estradiol and progesterone caplets subcutaneously at the time of
      ovariectomy. At gl9, rats were challenged with intravenous relaxin or isotonic
      saline and the brains were removed for study. Immunohistochemistry was performed
      on coronal brain sections, utilizing Fos as a marker of cellular activation. In
      the group receiving relaxin, Fos-like immunoreactivity (Fos-IR) was abundant only
      in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus as
      well as in the subfornical organ (SFO). In contrast, Fos-IR in the group given
      isotonic saline was lacking in these three brain regions. A double label study
      using antibodies against Fos and OT demonstrated that a majority of the Fos
      labeled cells in the hypothalamus were OTergic. Because Fos can act as a
      transcription factor, we interpret these data to indicate that transcription
      within OTergic cells is altered following relaxin administration, with abundant
      Fos-IR being limited to the SON and PVN of the hypothalamus and the SFO during
      late pregnancy in the rat.

PMID- 9258918
TI  - Effect of continuous intravenous injection of interleukin-6 and pretreatment with
      cyclooxygenase inhibitor on brain c-fos expression in the rat.
AB  - The aim of the present study was to assess potential brain sites of stimulation
      by peripheral interleukin (IL)-6 of the hypothalamo-pituitary-adrenal (HPA) axis
      in the rat, using c-fos protein as a marker of cellular activation. Involvement
      of prostaglandins in IL-6-induced ACTH secretion and c-fos expression was also
      investigated. IL-6 was infused continuously (40 ng/min) for 90 min to conscious
      male rats. Blood samples were taken before the infusion and at 30 and 90 min for
      measurement of plasma ACTH. Expression of c-fos in the brain was examined by
      immunohistochemistry. Administration of IL-6 significantly elevated plasma ACTH
      levels at 30 min (495 +/- 105 vs. 117 +/- 17 pg/ml in controls, p < 0.05).
      Elevated levels were still present at 90 min (596 +/- 139 vs. 113 +/- 20 pg/ml in
      controls, p < 0.05). Infusion of IL-6 (3.6 micrograms/rat) markedly triggered c
      fos expression in hypothalamic paraventricular (PVN) and supraoptic nuclei (SON),
      as well as in the central amygdaloid nucleus (CeA), the nucleus tractus
      solitarius and the locus coeruleus. Pretreatment with the cyclooxygenase
      inhibitor indomethacin (10 mg/kg, i.v.) suppressed the ACTH response induced by
      IL-6. The number of IL-6-induced immunoreactive cells in the PVN was
      significantly reduced by indomethacin pretreatment (p < 0.01), but the number of
      IL-6-induced c-fos-positive cells in the SON and CeA remained unchanged. These
      findings suggest that circulating IL-6 may exert central actions by acting
      directly or indirectly on brain neurons. In addition, the ability of IL-6 to
      activate the HPA axis may depend upon the release of prostaglandins, probably in
      the brain.

PMID- 9258919
TI  - Dose effects of recombinant human interleukin-6 on pituitary hormone secretion
      and energy expenditure.
AB  - Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major
      mediator of the effects of the immune system on several endocrine axes and
      intermediate metabolism. We performed dose-response studies of recombinant human
      IL-6 on pituitary hormone secretion in 15 healthy male volunteers, using 5
      single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0
      micrograms/kg body weight), each in 3 volunteers. We measured resting metabolic
      rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and
      vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All
      doses examined were tolerated well and produced no significant adverse effects.
      Dose-dependent RMR increases were observed in response to the 3.0- and 10.0
      microgram/kg doses of IL-6, beginning at 60 min and slowly peaking between 180
      and 240 min. Plasma adrenocorticotropic-hormone concentrations increased
      dramatically and dose-dependently in all the patients who received the 3.0- and
      10.0-microgram/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60
      min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels
      peaked dose-dependently between 90 and 150 min, but remained elevated throughout
      the sampling period. In contrast, the growth hormone (GH) dose-response was bell
      shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0
      micrograms/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response
      pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively
      decreased over the 240 min, while gonadotropins showed no clear-cut changes. In
      conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent
      increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting
      that hypothalamic corticotropin-releasing hormone may mediate both of these
      functions in humans. IL-6 also acutely stimulated GH and PRL secretion and
      suppressed TSH secretion. The dose of 3.0 micrograms/kg could be used safely in
      the study of patients with disturbances of the hypothalamic-pituitary unit or of
      thermogenesis.

PMID- 9258920
TI  - 2D time-of-flight MR angiography using concatenated saturation bands for
      determining direction of flow in the intracranial vessels.
AB  - We prospectively studied 15 patients to assess 2D time-of-flight (TOF) magnetic
      resonance angiography (MRA) with concatenated saturation bands for determining
      the direction of intracranial blood flow. This MRA sequence was compared to T2
      weighted spin-echo MRI, 3D-TOF MRA, and intra-arterial angiography (IAA) as
      regards demonstration of vessels and determination of the direction of flow in
      the circle of Willis and its branches. The 2D-TOF MRA sequence demonstrated flow
      in 98.5% vessel segments identified on IAA, 3D-TOF demonstrating 92% and spin
      echo images 77%. The direction of flow shown on the 2D-TOF sequence was correct
      in 94% when compared to conventional angiography, the remaining six segments not
      demonstrating flow. In ten patients, the flow abnormalities demonstrated by this
      MRA technique provided clinical information similar to that of conventional
      angiography in nine, but it was incomplete in three, and misleading in one. Slow
      retrograde flow in ophthalmic artery collaterals and differentiation of arteries
      and veins presented some problems. 2D-TOF MRA with concatenated saturation bands
      provides flow direction information using widely available, easily applicable TOF
      techniques, and can be a useful adjunct to MRI and MRA if information on flow
      direction is needed.

PMID- 9258921
TI  - Carotid MRA--what advantages do the turbo field-echo and 3D phase-contrast
      sequences offer?
AB  - Our purpose was to investigate some of the newer MR angiography (MRA) techniques
      for studying the carotid arteries. Forty-two arteries in seven asymptomatic,
      healthy volunteers were studied using five MRA sequences: two conventional time
      of-flight sequences, 2D time-of-flight (2DTOF) and 3D time-of-flight (3DTOF); 2D
      and 3D magnetisation-prepared, segmented time-of-flight sequences (2DTFE and
      3DTFE); and a 3D phase contrast angiography (3DPCA) sequence. A protocol that
      could be realistically employed in a routine clinical situation was chosen. 2DTOF
      had significantly (P < 0.05) better signal-to-noise ratio (SNR) and contrast-to
      noise ratio (CNR) than 2DTFE. 3DTOF demonstrated better SNR than 3DTFE but 3DTFE
      demonstrated better CNR than 3DTOF. 3DPCA provided maximal anatomical coverage.
      No one sequence provided optimal anatomical coverage, accurate demonstration of
      the carotid bulb and maximal SNR and CNR. The combination of 3DPCA and a 3D
      inflow sequence was best. 2DTOF sequences are useful when only one brief sequence
      is practicably feasible.

PMID- 9258922
TI  - Cortical laminar necrosis in brain infarcts: chronological changes on MRI.
AB  - We studied the MRI characteristics of cortical laminar necrosis in ischaemic
      stroke. We reviewed 13 patients with cortical laminar high signal on T1-weighted
      images to analyse the chronological changes in signal intensity and contrast
      enhancement. High-density cortical lesions began to appear on T1-weighted images
      about 2 weeks after the ictus. At 1-2 months they were prominent. They began to
      fade from 3 months but could be seen up to 11 months. These cortical lesions
      showed isointensity or high intensity on T2-weighted images and did not show low
      intensity at any stage. Contrast enhancement of the laminar lesions was prominent
      at 1-2 months and became less apparent from 3 months, but could be seen up to 8
      months.

PMID- 9258923
TI  - Filling defect sign in CT diagnosis of ruptured aneurysm.
AB  - We have encountered a ruptured aneurysm as a filling defect in cisternal blood on
      CT in patients with acute subarachnoid haemorrhage (SAH), as high-attenuation
      blood can act as a contrast medium. We term this finding the "filling defect
      sign". To evaluate the usefulness of the sign in the diagnosis of a ruptured
      aneurysm, we retrospectively analysed CT with 10-mm-thick slices obtained within
      2 days of onset of SAH in 100 consecutive patients. The sign was observed in 30
      of the 100 patients, and in 13 (68%) of 19 patients with a ruptured aneurysm more
      than 10 mm in diameter. The filling defect sign is useful in predicting the site
      of rupture.

PMID- 9258924
TI  - MR diffusion imaging of human intracranial tumours.
AB  - We used MRI for in vivo measurement of brain water self-diffusion in patients
      with intracranial tumours. The study included 28 patients (12 with high-grade and
      3 with low-grade gliomas, 7 with metastases, 5 with meningiomas and 1 with a
      cerebral abscess). Apparent diffusion coefficients (ADC) were calculated in a
      single axial slice through the tumours, the sequence was sensitive to diffusion
      along the cephalocaudal axis. Our main finding was that ADC in contrast-enhancing
      areas within cerebral metastases was statistically significantly higher than ADC
      in contrast-enhancing areas in high-grade gliomas (P < or = 0.05). Furthermore,
      the ADC in oedema surrounding metastases were statistically significantly higher
      the ADC in oedema around high-grade gliomas (P < or = 0.02). The ADC in patients
      with meningiomas did not differ significantly from those seen with high-grade
      gliomas or cerebral metastases. The highest ADC were found within cystic or
      necrotic tumour areas. In one patient with a cerebral abscess, suspected of
      having a high-grade glioma, the ADC was similar to that in high-grade gliomas.
      The finding of higher ADC in cerebral metastases than in high-grade gliomas may
      be helpful in trying to distinguish between these tumours preoperatively; it
      suggests increased free extracellular and/or intracellular water fraction in
      cerebral metastases. The method seems to hold potential for further noninvasive
      characterisation of intracranial tumours.

PMID- 9258925
TI  - Cranial aneurysmal bone cysts presenting with raised intracranial pressure:
      report of two cases.
AB  - Aneurysmal bone cysts in the skull vault are reported in two patients 7 and 9
      years old, who presented with vomiting and headaches caused by raised
      intracranial pressure. CT showed the cystic lesion in the diploe, with
      predominantly inward expansion. Fluid-fluid levels were seen on both CT and MRI;
      the latter also showed bleeding within the cyst. MR angiography showed
      compression of the superior sagittal sinus in the second case.

PMID- 9258926
TI  - Initial and follow-up MRI in a case of early diagnosed Reye's syndrome.
AB  - Early MRI in a case of clinically established Reye's syndrome confirmed CT
      findings of compressed ventricles and additionally demonstrated signal
      alterations in the thalamus, mesencephalon and pons. On follow-up MRI the pontine
      lesion had vanished by 1 week later, while the thalamic lesion persisted for more
      than 2 months. The patient, however, recovered without neurological sequelae.

PMID- 9258927
TI  - MRI of pituitary abscess: two cases and review of the literature.
AB  - Pituitary abscesses, rare lesions, may be divided into primary and secondary
      types. Primary pituitary abscesses occur within a previously healthy gland, while
      secondary abscesses arise within an existing lesion, such as an adenoma,
      craniopharyngioma, or Rathke's cleft cyst. Secondary abscesses share radiologic
      characteristics with the lesions from which they arise. There has been no review
      of the MRI characteristics of primary pituitary abscesses. We report two cases
      and review the literature. The typical primary pituitary abscess gives the same
      or slightly lower signal than brain on T1-weighted images, and could be mistaken
      for a solid mass or presumed to represent a pituitary adenoma. Contrast-enhanced
      images are useful, demonstrating absence of central enhancement, suggesting a
      fluid or necrotic center. In one of our cases, meningeal enhancement was obvious;
      this has not been reported previously and may be diagnostic, when associated with
      a rim-enhancing pituitary mass.

PMID- 9258928
TI  - Gadolinium enhancement of the cerebrospinal fluid in a patient with meningeal
      fibrosis and cryptococcal infection.
AB  - We describe the case of a 52-year-old man, with cryptococcal meningitis and
      meningeal fibrosis who had undergone ventricular shunting. Gd-DTPA-enhanced T1
      weighted MRI revealed diffuse meningeal enhancement. Remarkably, there was
      enhancement of the pia mater and posterior fossa subarachnoid space.

PMID- 9258930
TI  - Orbital hydatid cyst: CT and MRI.
AB  - Orbital hydatid cyst is rare. We present a case with CT and MRI, emphasizing the
      superiority of the latter.

PMID- 9258929
TI  - Sonography, CT, CT sialography, MRI and MRI sialography in investigation of the
      facial nerve and the differentiation between deep and superficial parotid
      lesions.
AB  - Our aim was to explore the possibility of delineation of the facial nerve within
      the parotid gland and to differentiate between superficial and deep parotid
      lesions in relationship to it, using ultrasound, CT, MRI, MRI sialography (MRIS)
      and CT sialography (CTS). We examined 47 patients with clinically suspected
      parotid tumours by US, 31 of them also by CT, MRI and CTS, and 13 by MRIS as
      well. Low-intensity curvilinear structures seen on T1-weighted MRI were
      delineated better after intraductal gadolinium injection and proved to represent
      parotid ducts on CTS. Using the main parotid duct as a landmark, we distinguished
      parotid lesions as deep or superficial to the facial nerve by T1-weighted MRI
      images in 69% and by MRIS in all cases. The facial nerve itself was
      indistinguishable from the parotid gland in all our imaging methods.

PMID- 9258931
TI  - Sarcoidosis presenting as an intra- or extra-axial cranial mass: report of two
      cases.
AB  - Sarcoidosis may also present as an extra- or intra-axial mass involving the
      central nervous system. These lesions are sometimes operated upon, because a
      neoplasm is suspected. We report two cases of unusual tumour-like extra- and
      intra-axial sarcoidosis. The extra-axial mass was just medial to the jugular
      foramen. Its morphology and signal characteristics differed from the more common
      lesions in this area. The intra-axial mass was in the temporal lobe, with only
      minor leptomeningeal involvement. Extra-axial sarcoidosis can be confused with a
      meningioma because these lesions can give relatively low signal on T2-weighted
      images. Intra-axial masses are presumed to represent a propagation and fusion of
      multiple leptomeningeal granulomas through the Virchow-Robin spaces in the brain;
      this pattern can be sought on contrast-enhanced T1-weighted images.

PMID- 9258932
TI  - Castleman's disease in the neck: MRI.
AB  - We describe a case of Castleman's disease in a 8-year-old-boy who presented with
      a slowly growing mass in the upper neck. MRI showed a well-defined homogeneous
      mass with nonspecific signal features. Unusual features were a kidney-bean shape
      and the deep location in the suprahyoid region, the mass originating in the left
      retropharyngeal space.

PMID- 9258933
TI  - Magnetization transfer in the investigation of patients with tuberous sclerosis.
AB  - We examined 21 patients aged 5 months to 19 years, on a 1.5 T magnet. T1-weighted
      spin-echo images, proton density and T2-weighted images with spin-echo and turbo
      spin-echo sequences, and contrast-enhanced magnetization transfer (MT) T1
      weighted images were obtained in all cases. MT T1-weighted images were performed
      before injection in 9 patients. Subependymal nodules were found in 14, and
      cortical and subcortical tubers in 20 of the 21 patients. MT T1-weighted images
      showed tubers and subependymal nodules as higher signal than normal gray matter
      and revealed more tubers than conventional sequences in 11 cases. High signal
      intensity lesions of the white matter were found in 19 patients but were seen
      only on MT images in 9 cases. When MT images both before and after injection were
      available, tubers and white matter lesions were more easily recognised on
      unenhanced MT images because of their higher contrast.

PMID- 9258934
TI  - Nasal dermoid cyst with a sinus tract extending to the frontal dura mater: MRI.

PMID- 9258935
TI  - How should we estimate carotid stenosis using magnetic resonance angiography?

PMID- 9258936
TI  - Isolation of HTLV-1 from an aggressive form of ATL in a Romanian patient not at
      risk of infection and with seronegative family members.
AB  - We present the clinical, virological and haematochemical data of a 22 year old
      patient from Romania with Adult T Cell Leukaemia (ATL). Viral isolation in
      peripheral mononuclear blood cells (PMBC), detection of DNA sequences of HTLV-1
      by Polymerase Chain Reaction (PCR) and of antibodies by Elisa and Western blot
      were performed. The patient does not belong to any risk group and additionally
      all members of her family are seronegative for HTLV-1, the aetiological agent of
      ATL. The role of viral infection remains open.

PMID- 9258937
TI  - SupT-1: a cell system suitable for an efficient propagation of both HHV-7 and HHV
      6 variants A and B.
AB  - HHV-7 growth on Sup-T1, an immature T-cell line, was studied using different HHV
      7 isolates obtained in our laboratory. Titration of viral yields showed that all
      the virus isolates propagate on this cell line more efficiently than in cord
      blood lymphocytes, the cells usually recommended for HHV-7 growth. The
      permissivity of Sup-T1 to HHV-6, whose ability to replicate in these cells was
      still unknown, was also investigated using two virus isolates representative of
      variants A and B respectively. Both isolates were able to propagate on Sup-T1 and
      viral titres were similar to those obtained in cord blood lymphocytes. As the
      efficient propagation of both HHV-7 and HHV-6 isolates in Sup-T1 cultures, these
      cells may replace more time consuming and expensive cord blood lymphocyte
      preparations for the propagation of both the viruses.

PMID- 9258938
TI  - Use of reverse-transcription polymerase chain reaction for detection of rubella
      virus RNA in cell cultures inoculated with clinical samples.
AB  - A recently developed reverse transcription-nested polymerase chain reaction (RT
      nPCR) method for rubella virus (RV) RNA detection was assessed in a series of
      African green monkey kidney (AGMK) cell cultures inoculated with clinical samples
      from patients with suspected RV infection. Results were compared with those of
      conventional virus isolation/identification. The assay included an internal
      control of amplification consisting of a synthetic RNA molecule mimicking the RV
      E1 target sequence. A semiquantitation of RV RNA was achieved by comparing the
      relative band intensity of internal control and RV E1 fragment. RT-nPCR was
      positive in 15/16 (94%) RV isolation-positive cultures and in 12/60 (20%) RV
      isolation-negative cultures. All 27 cell cultures positive by RT-nPCR had been
      inoculated with clinical samples taken from patients with ascertained RV
      infection or given RV vaccination and consisted of cells harvested 1-10 days
      after primary inoculation of clinical samples. No RV RNA was found in any of the
      cell cultures inoculated with 14 clinical samples from 6 patients in whom RV
      infection was excluded. When considering the time-course of RV infection, it was
      found that RV RNA could be detected as early as 4 days p.i. in 10/21 (48%), and
      by 7-10 days p.i. in 27/28 (96%) cell cultures, whereas by the same time RV was
      isolated in only 7/16 (44%) cell cultures. Semiquantitation showed that: i) viral
      RNA amount progressively increased with time; ii) cell cultures containing very
      low levels of viral RNA one week p.i. either required a few blind passages for
      virus recovery or remained negative for RV isolation. Finally, PCR inhibitors
      were found in 10/164 (6%) cell cultures examined. In conclusion, RT-nPCR proved
      to be very sensitive and very specific and greatly reduced RV detection time in
      inoculated cell cultures.

PMID- 9258939
TI  - Antigenic analysis of influenza viruses isolated in Thailand between 1991 and
      1994.
AB  - We studied the epidemiology of influenza viruses in Thailand by isolating them
      and comparing their antigenic features with those of Japanese isolates. Between
      1991 and 1994, 32 strains were isolated from 186 throat swab specimens. Twenty
      one of the 32 isolates were of type A, subtype H3N2, and 11 strains were type B.
      It was suggested that the isolates of type A, subtype H3N2, drifted antigenically
      from A/Beijing/352/89-like to A/Kitakyusyu/159/93-like variants used as reference
      strains for comparison. The type B isolates in 1991 were suspected to be
      antigenically different from those of B/Bangkok/163/90, Thailand, in HI tests.
      These 1991 isolates were similar to B/Mie/1/93, which was isolated in the latter
      half of the epidemic in Japan in winter 1992/1993.

PMID- 9258940
TI  - Adenovirus isolation from spleen lymphocytes of apparently healthy pigs.
AB  - A polyethylene glycol treatment was given to fuse KSEK6 cells, an established
      cell line derived from porcine embryo kidney, with the lymphocytes, separated
      from spleens of 35 apparently healthy slaughtered pigs. Eight cytopathic virus
      strains were isolated from the lymphocytes of these pigs. Two virus strains were
      isolated by inoculating the spleen tissue homogenates to KSEK6 monolayer
      cultures. All of viruses were identified as porcine adenoviruses according to
      their physicochemical, serological and immunological properties. One of these
      virus strains was serologically proved to be independent from six serotypes of
      porcine adenoviruses ever known. The electrophoretic property of viral DNA of
      this strain was indicated to be different from those of other reference porcine
      adenoviruses. This means the presence of a 7th serotype in porcine adenoviruses.

PMID- 9258941
TI  - Synergy and mechanism of interaction between pefloxacin and penicillin G against
      enterococci.
AB  - In vitro synergy between penicillin and pefloxacin against Enterococcus hirae and
      Enterococcus faecium strains with different penicillin susceptibility was
      studied. The combination was synergistic against penicillin-resistant strains. E.
      hirae R40 and E. faecium 28R, but not against the penicillin-susceptible ones (E.
      hirae ATCC 9790 and E. faecium 28S). Analysis of PBPs of cells, grown in the
      presence of pefloxacin, showed that PBP5 of penicillin-resistant strains, the PBP
      responsible for the resistance of enterococci to beta-lactam antibiotics, is
      consistently reduced while it is almost unaffected in the penicillin-susceptible
      strains even at the highest concentrations of pefloxacin. These results indicate
      that pefloxacin interferes with the mechanism of synthesis of PBPs and
      particularly of PBP5, a protein whose production has already been modified in
      resistant strains, in some way rectifying the previous alteration.

PMID- 9258942
TI  - The molecular epidemiology of trimethoprim-sulphamethoxazole- resistance of
      Shigella flexneri in the Trakya region of Turkey.
AB  - Trimethoprim-sulphamethoxazole (SXT) resistance increased among Shigella flexneri
      isolates in 1995 relative to previous years, in the Trakya region, the European
      part of Turkey. Since this region is the entrance to Turkey from northern
      countries, a heavy traffic of travellers passing through should have been
      importing or exporting the resistant isolates. We studied the genetic basis and
      epidemiology of this resistance and monitored the clonal changes which have taken
      place in the meanwhile. During the study period, a total of 70 Shigella spp. were
      isolated. Of these 58 were S. flexneri, 10 were S. sonnei and two were S. boydii.
      S. dysenteriae was not isolated. Of S. flexneri isolates 32 were SXT, ampicillin,
      chloramphenicol and tetracycline resistant (pattern I), while two isolates were
      found to be resistant only to SXT (Pattern II). Transconjugation experiments
      revealed that an approximately 80 Kbp self-transmissible plasmid carried the SXT
      resistance genes in both groups. However, EcoRI and HindIII restriction patterns
      of the plasmids from resistance pattern I and resistance pattern II were
      different. Ribotypes of three randomly selected isolates from pattern I were
      identical and were distinguishable from the ribotype of the isolate from pattern
      II. We concluded that at least two different clones with different plasmids and
      resistance patterns were spreading in our territory.

PMID- 9258943
TI  - Production of TNF alpha and interleukin 6 by differentiated U937 cells infected
      with Leishmania major.
AB  - Several cytokines play a crucial role in the defense of the host against protozoa
      belonging to the genus Leishmania. However, the role of tumor necrosis factor
      alpha (TNF alpha) and interleukin 6 (IL-6) in human leishmaniasis is still
      controversial. The aim of this work was to study, in an "in vitro" model, the
      interactions of human phagocytes with L. major. The U937 human monocytic cell
      line, differentiated with phorbol myristate acetate (PMA) or a combination of 1
      alpha,25 dihydroxyvitamin D3 (VD) and retinoic acid (RA), was used in all the
      experiments. The rate of infection, as well as the production of TNF alpha and IL
      6 by cells upon infection with promastigotes, were studied. It was found that,
      depending on the agent used for differentiation, U937 cells produced different
      patterns of cytokines. PMA differentiated cells produced significantly more TNF
      alpha, but less IL-6 than cells differentiated with VD-RA. No direct relationship
      was found between the ability of differentiated U937 cells to release TNF alpha
      or IL-6 and their leishmanicidal activity.

PMID- 9258944
TI  - The effect of different pectic growth substrates on beta-glucosidase in Fusarium
      oxysporum f. sp. radicis lycopersici: partial purification and characterization.
AB  - Fusarium oxysporum f. sp. radicis lycopersici produces beta-glucosidase
      activities when it grows on pectin and glucose. The pectins were better
      substrates than glucose. In the medium containing galacturonic acid or sucrose
      the activity was present in low levels and at the end of autolysis. A beta
      glucosidase from the pectin medium was purified by ion exchange chromatography
      followed by gel filtration. The enzyme was a unique band of protein in SDS-PAGE
      and isoelectric focussing. It had a molecular weight of 86,000 and a pI of 4.8.
      This beta-glucosidase was a glycoprotein.

PMID- 9258945
TI  - Antigenic profiles for the differentiation of Mobiluncus curtisii and Mobiluncus
      mulieris by immunoblotting technique.
AB  - The antigenic profile of 30 vaginal isolates of Mobiluncus strains (22 M.
      curtisii and 8 M. mulieris) was determined by immunoblotting technique using
      mouse immune ascitic fluids containing polyclonal antibodies against the type
      strains M. curtisii subsp. holmesii (ATCC 35242) and M. mulieris (ATCC 35243).
      Two antigenic profiles were identified within M. curtisii isolates, whereas a
      certain variability was observed among M. mulieris strains where at least three
      antigens were constantly recognized. The detection of antigenic profiles of
      Mobiluncus strains by immunoblotting technique provided a simple method to
      identify Mobiluncus isolates at the species level.

PMID- 9258946
TI  - Effect of treated sewage on the water quality and phytoplankton populations of
      Lake Manzala (Egypt) with emphasis on biological assessment of water quality.
AB  - The effect of treated sewage on the quality of water and phytoplankton
      populations of Lake Manzala was studied with emphasis on use of algae to monitor
      water pollution as part of a search for a biological assessment of water quality.
      Lake Manzala is situated at the northern part of the Nile-delta, Egypt. Disposal
      of treated sewage into Lake Manzala appeared to have differential effects on
      water quality and phytoplankton populations. Marked seasonal and local variations
      were observed for the physical and chemical characteristics of water. 157 species
      of algae were identified, 59 Chlorophyta, 37 Bacillariophyta, 30 Cyanophyta
      (Cyanobacteria), 28 Euglenophyta, one Pyrrhophyta and 2 Cryptophyta. Distribution
      and abundance of these algal divisions were found to differ at different sampling
      stations. Qualitative and quantitative growth of each algal division displayed
      great seasonal variations. The phytoplankton standing crop was mainly due to the
      contribution of Bacillariophyta whereas the species composition is dependent
      mainly on Chlorophyta. A great parallelism was noted between the quality of water
      samples based upon the chemical and physical investigations and their quality
      based upon the biological indices. Compound eutrophication index indicated that
      the nature of the investigated water ranged between eutrophic and hypereutrophic
      conditions. Diversity index values indicated that the water in the study area was
      of a moderate level of pollution. Saprobic index and saprobic quotient revealed
      the presence of beta- to alpha-mesosaprobic forms of algae.

PMID- 9258947
TI  - The use of radioimmune western blotting to evaluate indeterminate western
      blotting results in blood donor HIV serodiagnosis.
AB  - The serodiagnosis of HIV infection is sometimes puzzling due to questionable
      "indeterminate" results obtained by western blotting (wb), the confirmatory test
      used world-wide after a positive or borderline ELISA result. These situations
      cause anxiety in the person being tested and determine additional laboratory
      costs. We showed that radioimmune western blottting (riwb) an improved and
      sensitive modification of conventional wb, was able to resolve most
      "indeterminate" results in individuals who later fully seroconverted. We report
      in this paper the use of riwb in sera of 20 uninfected blood donors with an
      indeterminate wb continuing for at least 6 years, to verify the serological
      status in indeterminate not at risk individuals. Thirteen out of the 20 were
      indeterminate with conventional wb due to the presence of antibodies to p 24, two
      to p 17, two to p 55, two to p 51 and p 55 and one to p 24 and p 51 antibodies.
      The presence of all these bands was confirmed using riwb; moreover, in comparison
      with wb, the intensity of all bands was clearly enhanced. Despite the use of this
      highly sensitive method no new bands were found with riwb in indeterminate sera;
      negative results were obtained when sera borderline or positive with ELISA but
      negative with wb, were subjected to riwb.

PMID- 9258948
TI  - Use of hybridization assay and direct immuno assay for detection of Salmonella
      spp. in surface waters and a comparison with conventional culture procedure.
AB  - Hybridization assay and direct immunoassay for detecting Salmonella in
      contaminated surface waters have been compared with the conventional culture
      procedure. The 67 samples examined were taken from different rivers in the
      provinces of Catania and Ragusa. By culture method, Salmonella was isolated in 23
      samples (34%), while direct immunoassay revealed the presence of Salmonella in 58
      samples (87%) and the hybridization method identified Salmonella in 20 samples
      (30%). On the basis of the results obtained, the direct immunoassay method proved
      to be inaccurate for the high number of false positives revealed. The DNA probe
      test gave almost identical results to those obtained with the culture method,
      with notably shorter execution times than the latter. This test proved to be both
      sensitive and specific and could be used for the direct demonstration of
      Salmonella in surface waters where it is easier to find bacteria under stress
      from the environmental conditions, in waters where isolation is difficult, and in
      all those environmental control conditions which do not require isolation and the
      serological typing of the strains of Salmonella.

PMID- 9258949
TI  - Evaluation of post-exposure vaccination against rabies in cattle.
AB  - Post-exposure vaccination of bovines against rabies with three anti-rabies
      vaccines viz. BHK21 cell culture inactivated vaccine. "Raksharab", Vero cell
      culture vaccine and Semple's vaccine was studied with different schedules of
      vaccination. The mean RFFIT and ELISA titres of animals vaccinated with Raksharab
      and Vero cell culture vaccine reached a peak 95 days post-exposure (dpe). The
      animals vaccinated with Semple's vaccine showed maximum RFFIT and ELISA titres on
      40 dpe and the titres were lower than those induced by tissue culture rabies
      vaccines. All the calves vaccinated with Raksharab and Vero cell culture vaccine
      were protected. One out of six calves vaccinated with Semple's vaccine died of
      rabies on 16 dpe. All the control animals died of rabies between 14 and 22 dpe.
      Raksharab schedule of vaccination on days 0, 4, 7, 14, 28 and 90 dpe was
      effective when compared with other vaccines with similar and different schedules.
      Tissue culture rabies vaccine is superior to nervous tissue vaccine in eliciting
      satisfactory immune response required to protect animals exposed to virulent
      rabies virus.

PMID- 9258950
TI  - The teaching of pathology in undergraduate education programs in medicine in
      Europe.

PMID- 9258951
TI  - Heterogeneity of systemic extra-nodal Epstein-Barr virus-associated lympho
      histiocytic tumor--ten autopsy cases of human immunodeficiency virus-negative
      Japanese.
AB  - Epstein-Barr virus associated T-Cell lymphoma mimicking malignant histiocytosis
      (MH) has been previously reported. We selected 10 autopsy cases of extranodal
      lymphoma or histiocytic tumor, which showed an EBV presence in the tumor cells as
      well as a fulminant clinical course. The detailed clinicopathologic features were
      thus clarified. A retrospective study was performed on ten adult patients, eight
      males and two females, and almost all cases presented with a fulminant clinical
      course, revealing pancytopenia, liver dysfunction and disseminated intravascular
      coagulopathy. Immunophenotypic and genotypic studies along with in situ
      hybridization (ISH) were performed. The autopsy findings mainly showed extra
      nodal involvement in the liver (10 patients), spleen (9 patients), intestinal
      tract (5 patients), bone marrow (5 patients), nasal cavity, lungs, adrenal
      glands, kidneys (2 patients) and brain. Histologically atypical pleomorphic
      lymphoid cells were observed to infiltrate with reactive histiocytes, some of
      which showed hemophagocytosis. Based on the histological and clinical findings,
      diagnosis of malignant histiocytosis was made. ISH showed an EBV-presence in
      almost all the tumor cells. The immunophenotype and/or genotype studies
      demonstrated T-cell lymphoma (2 patients), Histiocytic tumors (2 patients), B
      cell lymphoma (1 patients), natural killer (NK) cell lymphoma (3 patients), and
      T/NK lymphoma (2 patients), in which T or NK could not be confirmed, due to a
      lack of fresh materials. Based on the above findings, the histological appearance
      of EBV-associated MH previously defined was shown to be common to extra-nodal
      malignant lymphomas having origin in various organs, although the cytological and
      genetic features were heterogenous.

PMID- 9258952
TI  - Angiogenesis in breast cancer is related to age but not to other prognostic
      parameters.
AB  - Angiogenesis is essential for tumour growth and metastasis. In spite of its
      relevant biological significance, recent studies have produced conflicting
      results regarding the capacity of microvessel quantifications in breast
      carcinomas to predict patients' outcome and the existence of metastasis. In order
      to provide further information in this issue, we evaluated tumour angiogenesis in
      a series of 45 primary breast carcinomas (mean age: 55.3 +/- 14.2) and examined
      their association with established or potentially useful prognostic parameters.
      Microvessels were highlighted by immunohistochemical staining for factor VIII
      related antigen and counted in the three most vascularized areas in a 200 x field
      (0.74 mm2) by four observers simultaneously. Results were analysed for the
      average vessel count of each case. The mean intratumoural microvessel count was
      57.7 +/- 24.4 (range: 24.3 to 127.7). We found a statistically significant
      association between angiogenesis and age. The microvessels count in patients
      younger than 50 years was 67.8 +/- 26.4, from 51 to 70 years, 52.0 +/- 22.8 and
      over 71 years, 46.1 +/- 14.2 (p = 0.03). Node positive patients had slightly
      higher microvessel counts (60.3 +/- 25.3) than node negative ones (54.4 +/-
      23.5); this difference was not significant (p = 0.42), even when we considered
      each age group per se. No association was found between angiogenesis and tumour
      size, histologic grade, estrogen receptor, MIB-1 index, ploidy and expression of
      p53 and c-erbB-2. Our results suggest that invasive breast carcinoma-induced
      angiogenesis is age-dependent.

PMID- 9258953
TI  - Silver-stained nucleolar organizer regions in adenocarcinoma of the cervix--a
      light and electron microscopic study.
AB  - An increase in the number of Ag-NORs has been described as a possible marker for
      histopathological cancer diagnosis. The ultrastructural correlation of the
      reaction, however, has never been elucidated. In tissue samples of the endocervix
      of the uterus, we compared the ultrastructural configuration of Ag-NORs with the
      number of Ag-NORs dots. Light microscopic studies showed that the number of Ag
      NORs in adenocarcinoma cells significantly increased, but the relation to the
      bromodeoxyuridine labeling index was not determined. By electron microscopy, Ag
      NORs were only observed in the nucleoli and the nuclear bodies of nuclei. Ag-NORs
      were localized on all components of the nucleolar structure, but the dense
      fibrillar component was the predominant site in several cases. The nuclear bodies
      were exclusively found in adenocarcinoma cells and were argyrophilic. A spotted
      distribution of Ag-NORs was often found in the nucleoli of adenocarcinoma cells
      that showed an increased Ag-NOR count. The number of Ag-NORs was attributed not
      only to the number of nucleoli and nuclear bodies in a nucleus but also to the
      speckled distribution of silver deposits in a nucleolus. These results imply that
      the Ag-NOR count is a more definitive indicator of a hyperactive state of the
      cells than the combined number of nucleoli and nuclear bodies in adenocarcinoma
      of the uterine cervix.

PMID- 9258955
TI  - Neutral and acid mucins and eosinophil and argyrophil crystalloids in carcinoma
      and atypical adenomatous hyperplasia of the prostate.
AB  - Neutral and acid mucins and eosinophil and argyrophil crystalloids were studied
      in the glandular intraluminal contents of 130 prostatic carcinomas (PCa) and 22
      atypical adenomatous hyperplasias (AAH). Specimens were studied in the usual
      extension for diagnostic purposes and considered positive when minimal amounts of
      mucin or any crystalloid were present. Some amount of altered secretion was seen
      in 110 PCa (84.6%) and in 17 AAH (77.3%); the similarity of the figures speaks
      for the close relationship of these lesions. The relative incidences in PCa/AAH
      were 61.5%/77.3% for neutral mucin, 80%/54.5% for acid mucin (p < 0.01),
      25.4%/50% for eosinophil crystalloids (p < 0.02), 44.6%/9.1% for argyrophil
      crystalloids (p < 0.01) and 57%/36% for a compound secretion. The incidence of
      eosinophil crystalloids was greater in AAH and inversely proportional to the
      Gleason grade in PCa. The incidence of acid mucins and argyrophil crystalloids
      was higher in PCa and directly proportional to the tumour grade in all but the
      poorly differentiated ones. It is therefore suggested that AAH positive for acid
      mucins or argyrophil crystalloids be classified in the high grade AAH group.

PMID- 9258954
TI  - Endometrial carcinomas--flow cytometric DNA content and S-phase values.
AB  - The purpose of the investigation was to determine the DNA content and S-phase
      value in a large material of fresh tumour tissue from endometrial carcinomas and
      to correlate these parameters to tumour type, grade of differentiation, depth of
      myometrial invasion and stage. The prospective study consisted of 290 unselected
      cases of endometrial carcinomas, FIGO stage I-IV where flow cytometry was
      performed on fresh tumour tissue blocks from hysterectomy specimens. 223 cases
      had more than 10% tumour tissue in tissue blocks taken adjacent to the blocks for
      flow cytometry. Non-diploidy was defined as 0.9 > or = DNA index > 1.10 and high
      S-phase value was defined as > 15%. Non-diploidy was found in 46% of the
      endometrioid adenocarcinoma and in 85% of the non-endometrioid carcinomas (clear
      cell adenocarcinoma, serous adenocarcinoma and malignant mixed mesodermal tumour)
      (p < 0.001). S-phase value was > 15% in 39% of the endometrioid adenocarcinoma
      and in 100% of the non-endometrioid carcinomas (p < 0.0001). In endometrioid
      adenocarcinoma there was a statistical significant relation between non-diploidy
      and grade of histological differentiation (p < 0.006), as well as with depth of
      myometrial invasion (p < 0.05). There was no relation between non-diploidy and
      the presence of squamous differentiation, whether benign or malignant or to FIGO
      stage. High S-phase values (> 15%) was related to the grade of differentiation (p
      < 0.002). No relation was demonstrated between S-phase > 15% and squamous
      differentiation, depth of myometrial invasion or FIGO stage. In conclusion, 50%
      of all the endometrial carcinomas were non-diploid and 43% had S-phase value >
      15%. Ploidy correlated with histologic tumour types, grade of differentiation and
      depth on myometrial invasion while S-phase values only correlated with histologic
      tumour types and grade of differentiation.

PMID- 9258956
TI  - Immunodetection of c-met-oncogene's protein product in renal cell neoplasia.
AB  - The proto-oncogene c-met encodes a transmembrane tyrosine kinase receptor for
      hepatocyte growth factor and is expressed in normal kidney tissue. This receptor
      may be involved in the carcinogenesis of various organs. The aim of this study
      was to investigate the relationship between c-met immunohistochemical expression
      and pathological tumor variables in human renal cell carcinomas (RCCs) and
      adenomas (RAs). Formalin fixed, paraffin embedded tissues from 35 RCCs, 16 RAs
      and 17 normal kidneys were immunostained (Strept. ABC/HRP) with a polyclonal
      antibody against c-met protein (Santa Cruz, Clone C-12). The statistical analysis
      was performed using the linear trend in proportions and Fisher's exact test. C
      met protein was detected in the cytoplasm and the plasma membranes of neoplastic
      cells in 19/35 RCCs (54%), 10/16 adenomas (63%) (p = 0.41) and in 17/17 controls
      in the epithelial cells of distal renal tubules and collecting ducts. C-met
      protein expression was not related with gender (p = 0.45), age (p = 0.18), tumor
      size (p = 0.99), cell type (p = 0.26), grade (p = 0.86) and stage (p = 0.33).
      Moreover, c-met immunopositive tumor cell percentage and intensity were increased
      in stage [RCCs, but these results were not statistically significant. Apart from
      glandular differentiation, c-met protein expression was not related to other
      histopathological features (i.e. to the type of cells or to any selective
      overexpression in tumor cells). C-met product may be involved in the malignant
      transformation of tubular epithelial cells as an early event in RCC
      carcinogenesis. C-met expression does not seem to have any prognostic
      significance for RCCs, as it was not associated with any pathological
      prognosticator.

PMID- 9258957
TI  - Intranuclear mitochondria in human myocardial cells.
AB  - Intranuclear mitochondria have occasionally been reported in various cells
      including cardiac myocytes, but the incidence and details including the specific
      mechanism(s) whereby mitochondria exist in the nuclear matrix are unknown. We
      studied the ultrastructure of a total of 91 consecutive endomyocardial biopsy
      specimens obtained from 50 patients with various cardiac diseases. Intranuclear
      mitochondria were found in three patients: two with hypertrophic cardiomyopathy
      and one with chronic myocarditis. Their myocytes were markedly hypertrophic and
      the shapes of the nuclei were bizarre. Specimens from these patients were further
      studied on serial sections, and some of the nuclei with mitochondria showed
      ruptured nuclear envelope. Intranuclear mitochondria were found in at least 6% of
      the patients with cardiac diseases (3% of the specimens examined), and a novel
      mechanism of the pathogenesis was documented: communication between the nuclear
      matrix and cytoplasm through the rupture in the nuclear envelope. The nuclear
      rupture might be simply due to a laboratory artifact. On the other hand, it might
      imply some pathophysiological significances in the degeneration of myocytes in
      cardiac diseases.

PMID- 9258958
TI  - Molecular identification of foreign inclusions in inflammatory tissue surrounding
      metal implants by Fourier transform laser microprobe mass spectrometry.
AB  - Fourier transform laser microprobe mass spectrometry (FT LMMS) is a novel
      technique for micro-analysis of solids with a lateral resolution in the 5 microns
      range. One of the major advantages of the technique is the capability to perform
      characterisation of the molecular composition of both organic and inorganic
      compounds. The information is directly deduced from the signals without the aid
      of reference spectra. FT LMMS was applied to the characterisation of black tissue
      fragments in a biopsy from a patient, in which a constrained condylar nodular
      knee system was implanted ten years ago. The tissue contained numerous foreign
      giant cells with a black non-birefringent pigment in their cytoplasm. FT LMMS
      analysis allowed us to detect directly by means of molecular signals, that the
      debris consisted primarily of titanium oxide and not metallic titanium, while the
      implant itself only contained titanium.

PMID- 9258959
TI  - True histiocytic lymphoma as a second neoplasm in a follicular centroblastic
      centrocytic lymphoma.
AB  - We report on a patient who developed a true histiocytic lymphoma, 16 years after
      initial diagnosis of a follicular low grade centroblastic-centrocytic lymphoma
      with several recurrences. We consider, out of gene rearrangement and
      immunohistochemical studies, that in this case, true histiocytic lymphoma is a
      second neoplasm in the evolutive course of the low grade lymphoma. The natural
      history of a low grade malignant lymphoma is to develop into a high grade large
      cell lymphoma and, if a second neoplasm appears, it is usually an epithelial
      tumor. This fact makes our report unique, as it would be, to our knowledge, the
      first case of true histiocytic lymphoma as the second neoplasm of another
      lymphoma.

PMID- 9258960
TI  - Neurophysiological assessment of brain function and maturation. II. A measure of
      brain dysmaturity in healthy preterm neonates.
AB  - Severe brain disorders can be expressed as markedly abnormal encephalopathic EEG
      patterns in neonates who are usually neurologically depressed, with abnormal
      levels of reactivity and tone. This symptomatic group is now a minority of
      medically ill neonates as a result of more vigorous fetal and neonatal
      resuscitative efforts. Most neonates alternatively express brain dysfunction as
      more pervasive alterations in EEG-sleep organization or maturation, usually in
      the absence or after resolution of abnormal clinical signs. One form of
      dysfunction is expressed as neurophysiologic dysmaturity. Brain dysmaturity may
      reflect altered rates of development in infants who sustained prenatal or
      postnatal stresses, as discussed in the first part of this review. We now
      summarize our findings of dysmature EEG-sleep development at conceptional term
      ages in an asymptomatic preterm cohort during a prolonged extrauterine period
      before discharge from the nursery. Dysmaturity of EEG-sleep function was
      expressed as delayed and/or accelerated physiologic behaviors, as compared with
      behaviors expected for the conceptional age. Dysmature brain function at
      conceptional term ages was also associated with poorer neurodevelopmental
      performances at 12 and 24 months of age. Neuronal pathways which subserve state
      specific neurophysiologic behaviors will functionally adapt to stress by either
      slowing or accelerating neurological maturation. Through ontogenetic brain
      adaptation, which continues during postnatal development, a balance is maintained
      between the needs of the present developmental stage and anticipated needs during
      subsequent stages of maturation. How medical complications and environmental
      influences interact to promote greater brain dysmaturity in the neonate is still
      unknown. EEG sleep study can serve as a useful neurophysiologic screening
      procedure for the child suspected of having a subclinical presentation of an
      emerging static encephalopathy; longitudinal studies will then document
      deviations from expected ontogeny in the vulnerable child who is later stressed
      by environmental and socioeconomic factors.

PMID- 9258961
TI  - Characteristic neuropathology of leukomalacia in extremely low birth weight
      infants.
AB  - Extremely low birth weight (ELBW) infants with periventricular leukomalacia (PVL)
      were examined by neuropathological and immunohistochemical methods. Thirteen ELBW
      infants of 85 infants with PVL, born at 23 to 27 weeks of gestation, showed a
      widespread type of distribution of PVL from the deep to intermediate white
      matter. Immunohistochemistry demonstrated glial fibrillary acidic protein (GFAP)
      positive astrocytes to be increased in the deep white matter, often spreading to
      the intermediate white matter, in all cases of PVL. Tumor necrosis factor-alpha
      (TNF-alpha)-positive cells were found in the deep to intermediate white matter in
      69% of PVL cases and appeared earlier, from 23 weeks of gestation, than in
      controls. beta-Amyloid precursor protein (beta APP)-positive axons were found
      around PVL in the deep to intermediate white matter in 85% of the cases. In age
      matched control ELBW infants, GFAP-, TNF-alpha-, or beta APP-positive cells were
      never found. Therefore, in ELBW infants, widespread axonal damage and glial
      activation with cytokine production occur in the progression in characteristic
      PVL lesions.

PMID- 9258962
TI  - Diet- and valproate-induced transient hyperammonemia: effect of L-carnitine.
AB  - Hyperammonemia is an adverse effect of valproate (VPA) treatment. In particular,
      transient hyperammonemia has been reported to occur in VPA-treated patients after
      protein-rich meals. This phenomenon may occur secondary to a VPA-mediated
      carnitine insufficiency. We sought to confirm that protein ingestion would result
      in transient hyperammonemia and to determine whether supplementation with L
      carnitine would prevent this effect. We studied the effect of consumption of a
      standardized protein-rich meal (45 g protein) before (phase I) and after (phase
      II) administration of L-carnitine 50 mg/kg/day for 7 days in 11 epileptic
      children (13.3 +/- 2.3 years of age) receiving VPA. Venous blood was obtained
      during fasting (baseline) and at 2 and 4 hours after the protein-rich meal for
      analysis of ammonia (NH3), and VPA concentrations. Mean VPA trough concentrations
      did not differ significantly at any time. After protein ingestion, 2-hour NH3
      concentration increased by 86% (P < .05) from baseline in phase I as compared
      with a 38% increase in phase II. In both phases I and II, 4-hour NH3
      concentrations decreased toward baseline values. We conclude that (1) modest
      protein ingestion can result in significant transient increases in NH3 in VPA
      treated children, (2) significant increases may occur in patients with normal
      fasting NH3 concentrations, (3) these increases can be significantly attenuated
      by L-carnitine supplementation, and (4) these changes do not appear to be related
      to changes in VPA concentration.

PMID- 9258963
TI  - Late improvements in mobility after acquired brain injuries in children.
AB  - The purpose of this investigation was to describe the late improvements in
      functional mobility in children who have sustained severe acquired anoxic or
      traumatic brain injuries. Ninety-eight children from a consecutive series of 199
      with acquired brain injuries met inclusion criteria. As expected, children with
      traumatic injuries had better mobility at time of discharge from rehabilitation
      than did children with anoxic injury. In addition, children with traumatic
      injuries improved more in mobility status during the first 2 years after injury
      than did children with anoxic injury. The children who continued to improve in
      mobility after discharge were unconscious for a shorter time. Children who became
      community ambulators during the first year after discharge had higher mobility
      ratings at discharge. Although children who eventually achieved more functional
      mobility were admitted to rehabilitation service sooner after injury,
      discriminant analysis revealed that the duration of unconsciousness, and
      therefore severity of injury, was more closely correlated with the final mobility
      status.

PMID- 9258964
TI  - Ocular abnormalities in Down syndrome: an analysis of 140 Chinese children.
AB  - One hundred forty Chinese children with Down syndrome (DS) treated in the Child
      Assessment Centre of the Duchess of Kent Children's Hospital in Hong Kong between
      1985 and 1996 underwent a detailed ophthalmologic evaluation, including test of
      visual acuity by behavioral testing or retinoscopy, determination of ocular
      motility, visual field examination, binocular examination for strabismus,
      determination of near point convergence and pupillary reflex, and/or slit lamp
      bimicroscopy and ophthalmoscopy to assess ocular health. Only 43 children (31%)
      had no ocular abnormalities. The overall incidence of ocular abnormalities was
      69%, and included refractive error (58%), strabismus (20%), nystagmus (11%),
      blepharitis/conjunctivitis (7%), lens opacities (4%), and glaucoma (0.7%). No
      child had Brushfield spots or keratoconus. The incidence of refractive errors
      increased with increasing age and nearly doubled at school age. As compared with
      white children with DS, the Chinese children with DS exhibited a higher incidence
      of refractive error and a similar incidence of lens opacities but a lower
      incidence of strabismus, nystagmus, blepharitis, Brushfield spots, and
      keratoconus. Regular visual surveillance, especially of visual acuity, in
      children with DS as they mature is important in preventing amblyopia.

PMID- 9258965
TI  - Haplotype analysis of congenital myotonic dystrophy patients from asymptomatic DM
      father.
AB  - We report a family with congenital myotonic dystrophy (CDM) transmitted from an
      asymptomatic DM father; we analyzed the haplotype of this family by using
      polymorphism within and by flanking the DM protein kinase locus. One patient with
      congenital DM was homozygous for all markers studied, except for the expanded CTG
      repeats. Two other patients with congenital DM were heterozygous. One patient
      with congenital DM who was homozygous had greater clinical severity and more
      expanded CTG repeats than other CDM patients who were heterozygous. The
      asymptomatic father had a DM protomutation.

PMID- 9258967
TI  - The Aircardi-Goutieres syndrome: variable clinical expression in two siblings.
AB  - We report 2 siblings with the Aicardi-Goutieres syndrome (encephalopathy, basal
      ganglia calcifications, and persistent cerebrospinal fluid pleiocytosis). The
      eldest sibling is severely retarded; his younger brother has only mild, slowly
      progressive neurological deficits. To our knowledge, such a striking difference
      in clinical expression has not been reported previously.

PMID- 9258966
TI  - Cranial computed tomography scans of premature babies predict their eventual
      learning disabilities.
AB  - It remains difficult to predict, early enough to intervene effectively, the risk
      of the development of learning disabilities among extremely low birth weight
      (ELBW) infants (birth weights less than 1,000 g). We prospectively studied the
      relationship between dilatations of lateral ventricles of the cranial computed
      tomography (CT) scan taken at the postconceptional age of 40 weeks and learning
      disabilities in their school age. Using a computer digitizer, we measured the
      areas of ventricles on cranial CT scans. The mean area of lateral ventricles of
      the learning disabilities-suspected group was significantly larger than that of
      the control group (392.9 and 277.4 mm2, respectively; P < .01). There were no
      significant differences between the two groups in gestation, birth weight,
      physical measurements, and developmental quotients at early school age. The
      dilatation of the lateral ventricles assessed by cranial CT at the corrected term
      may be one of the first predictors of learning disabilities recognizable at early
      school age.

PMID- 9258969
TI  - Electrophysiological brainstem dysfunction in a child with Leigh disease.
AB  - We evaluated brainstem dysfunction in a girl with Leigh disease.
      Neuroradiological and neurophysiological tests included brain magnetic resonance
      imaging, [123I]IMP single-photon emission computed tomography (SPECT), auditory
      brainstem responses (ABRs), short-latency somatosensory evoked potentials
      (SSEPs), electrically elicited blink reflexes (BRs) and all night polysomnography
      (PSG). The basal ganglia and midbrain contained areas of low accumulation on
      [123I]IMP SPECT images. Serial analysis of ABRs and SSEPs showed progressive
      disturbances of the brainstem wave components. The R2 components of the BRs were
      impaired. All night PSG revealed disturbances in both the tonic and phasic
      components of REM sleep. These findings suggested the multimodality tests in
      combination with neuroradiologic examinations are useful for assessing brainstem
      dysfunction in patients with Leigh disease.

PMID- 9258968
TI  - Familial Dandy-Walker malformation and leukodystrophy.
AB  - We report the first familial cases with two different types of posterior fossa
      cystic malformation and a leukodystrophic-like aspect on cerebral magnetic
      resonance imaging (MRI). The girl and her brother had severe encephalopathy,
      marked hypotonia, absent deep tendon reflexes, macrocrania, gigantism, and
      dysmorphic face and extremities. The girl had generalized seizures. The boy had
      unilateral cataract and bilateral optic atrophy. The parents were first cousins,
      suggesting autosomal recessive transmission. MRI showed Dandy-Walker variant in
      the girl, with cerebellar vermis hypoplasia and expansion of the cisterna magna,
      which communicated with the fourth ventricle. Her brother had mega cisterna magna
      communicating with the fourth ventricle and a normal cerebellum. The 2 children
      had abnormally high signal in the supratentorial white matter. Visual and
      auditory evoked potentials revealed prolonged latencies. Motor and sensory
      conduction velocities were normal. Muscle and nerve biopsies were normal.
      Metabolic exploration demonstrated no abnormality.

PMID- 9258970
TI  - Opsoclonus-myoclonus syndrome with abnormal single photon emission computed
      tomography imaging.
AB  - The single photon emission computed tomography (SPECT) findings in 2 patients
      with opsoclonus-myoclonus syndrome (OMS) who had similar symptoms in the acute
      stage of the disease are described. In 1 patient with encephalitis, SPECT showed
      increased blood flow in most of the cerebellum; the highest accumulation of the
      radiotracer was found in the cerebellar vermis and neighboring structures. These
      changes disappeared with clinical improvement. In the other patient with chronic
      OMS, SPECT demonstrated hypoperfusion in most of the cerebellum. Our results
      suggest that the cerebellum, particularly its middle portion, is involved in the
      generation of OMS. SPECt is a useful method that enables us to detect in vivo
      functional impairment in patients with OMS.

PMID- 9258971
TI  - Valproate-induced liver failure in one of two siblings with Alpers disease.
AB  - Alpers disease is a neurodegenerative disorder of childhood characterized by
      early developmental delay, intractable seizures, and death in childhood.
      Neuropathologic changes are most severe in the gray matter and consist of diffuse
      neuronal loss, spongiform changes, and astrocytosis. We report 2 siblings with
      Alpers disease who were discordant for exposure to valproate (VPA). Both had
      developmental delay, and a progressive seizure disorder beginning at 5 years of
      age. The proband died at age 8 years of complications of ongoing seizures,
      including epilepsia partialis continua, with only minimal liver abnormalities.
      Her younger brother was treated with VPA for new-onset seizures and developed
      fulminant liver failure 6 months later, which led to his death at 5 years of age.
      Neuropathologic abnormalities of both siblings were consistent with Alpers
      disease. These observations support classification of Alpers disease and Alpers
      disease with liver cirrhosis as a single disease. They also confirm previous
      reports indicating that VPA may accelerate fulminant liver failure in Alpers
      disease. We recommend that a diagnosis of Alpers disease be considered in
      children with unexplained early developmental delay, cerebellar signs, or partial
      seizures, especially epilepsia partialis continua. When Alpers disease is
      strongly suspected, use of VPA should be avoided.

PMID- 9258973
TI  - Cystic leukoencephalopathy in a megalencephalic child: clinical and magnetic
      resonance imaging/magnetic resonance spectroscopy findings.
AB  - A neurodegenerative disorder characterized by megalencephaly since early infancy
      and slowly progressive symptoms of cerebellar, pyramidal, and extrapyramidal
      dysfunction, pseudobulbar signs, and epilepsy was detected in an 8-year-old girl
      with severe neuromotor handicap but preservation of mental and sensory functions.
      Cranial computed tomography and magnetic resonance imaging revealed brain
      swelling as well as severe abnormalities of frontal, temporal, and parietal white
      matter, with an extended cystlike appearance isointense to cerebrospinal fluid.
      Localized proton magnetic resonance spectroscopy of affected cystic white matter
      showed a loss of all metabolites, in accordance with a complete disintegration of
      neuroaxonal and glial tissue. This case is likely a severe variant of a recently
      described megalencephalic leukoencephalopathy with swelling and discrepantly mild
      clinical course.

PMID- 9258972
TI  - Respiratory failure in nemaline myopathy.
AB  - Four patients with nemaline myopathy, 1 with the severe infantile form and 3 with
      the benign congenital (classical) form, exhibited significant respiratory
      problems. In the patient with the severe infantile form, respiratory failure
      paralleled the generalized muscle weakness, whereas the 3 patients with the
      benign infantile form suddenly developed respiratory failure while still
      ambulant. Polysomnographic studies performed on 2 patients revealed that apnea or
      irregular thoracic movements occurred only during rapid eye movement sleep, when
      hypercapnia was also demonstrated on serial transcutaneous partial O2 and partial
      CO2 monitoring. A discrepancy between motor ability and respiratory involvement
      probably is not uncommon in patients with the moderate congenital form of
      nemaline myopathy. Clinicians must always be alert to respiratory failure when
      monitoring patients with nemaline myopathy.

PMID- 9258974
TI  - Failure of absorption of baclofen after rectal administration.
AB  - We wished to determine the degree to which baclofen was absorbed from an aqueous
      vehicle after rectal administration. A comparison was made to absorption after
      oral administration. After oral administration, the baclofen half-life was 2.3 to
      3.4 hours and peak serum concentrations were achieved from 1 to 2.1 hours after
      administration. No measurable absorption was observed after rectal administration
      of the drug in any subject. Rectal administration of baclofen is not a clinically
      sound treatment option when oral administration of the drug is not possible. For
      patients receiving chronic baclofen therapy, other medications such as a
      benzodiazepine should be considered at times when oral administration of
      medication is not possible.

PMID- 9258975
TI  - Pemoline associated hepatic failure: a critical analysis of the literature.

PMID- 9258976
TI  - Longitudinal examination of ... a population ... with autistic disorder.

PMID- 9258977
TI  - Reminiscent meanderings through most of a mainly pharmacological life.

PMID- 9258978
TI  - Cardiovascular actions of chronic intracerebroventricular administration of
      metformin in normotensive rats.
AB  - Acute intracerebroventricular administration of the antihyperglycaemic agent
      metformin (0.25-1 mg) elicits sympathoinhibitory responses in spontaneously
      hypertensive rats. However, cardiovascular actions of chronic
      intracerebroventricular metformin administration are unknown. To define the dose
      response relationship during chronic intracerebroventricular metformin
      administration, mean arterial pressure, heart rate, and locomotor activity were
      measured continuously by radiotelemetry in 40 normotensive rats. After a 10 day
      control period, an intracerebroventricular cannula was implanted and connected to
      an osmotic minipump which delivered metformin in the following doses: 0 [saline].
      0.01, 0.1, 1, and 10 mg/day. LD50 was 1.5 mg/day. Metformin, 1 mg/day attenuated
      the nocturnal, physiological increase in mean arterial pressure (-7.3 +/- 1.6%
      versus before metformin), produced behavioural changes and tended to increase
      locomotor activity. Lower doses of intracerebroventricular metformin (0.1 and
      0.01 mg/day) did not affect mean arterial pressure, heart rate or locomotor
      activity. In conclusion, chronic intracerebroventricular administration of high
      dose metformin (1.0 mg/day) attenuates the nocturnal, physiological increase in
      mean arterial pressure. These findings are compatible with a toxic,
      sympathoinhibitory action of high doses of metformin intracerebroventricularly.

PMID- 9258979
TI  - Stretch-induced stimulation of lower airway nitric oxide formation in the guinea
      pig: inhibition by gadolinium chloride.
AB  - The effect of stretch on lower airway nitric oxide formation was studied in
      normoxic tracheostomized anaesthetized guinea-pigs. Increase of level of positive
      end-expiratory pressure caused increased lower airway nitric oxide formation, as
      measured by its presence in exhaled tracheal air. The L-type calcium channel
      blocker, verapamil, did not decrease lower airway nitric oxide formation. Neither
      the local anaesthetic xylocaine nor the ganglion blocker trimetaphan affected
      exhaled nitric oxide, excluding local and centrally-mediated neuronal reflexes.
      Intravenous administration of gadolinium chloride (GdCl3, 50 mg/kg) induced a
      rapid and pronounced decrease (75%) in the basal level of exhaled nitric oxide.
      GdCl3 completely abolished lower airway nitric oxide formation induced by
      ventilation with positive end-expiratory pressure (7 cm H2O). GdCl3 induced
      hypoxaemia, but there was no indication for the development of lung oedema. The
      results indicate that positive end-expiratory pressure stimulates lower airway
      nitric oxide formation in the guinea-pig. GdCl3 inhibits lower airway nitric
      oxide formation in the guinea-pig in vivo, perhaps by interference with stretch
      induced cellular calcium-influx.

PMID- 9258981
TI  - No effect of diclofenac on the pharmacokinetics of cloxacillin.
AB  - We studied the influence of diclofenac on the pharmacokinetics of cloxacillin in
      healthy volunteers, 60 years or older, as well as the possible effect of
      cloxacillin and diclofenac on urinary protein excretion. In a randomized, double
      blind, cross-over study 15 subjects were given 1 g cloxacillin, and placebo or 75
      mg diclofenac, as single intravenous doses. Plasma concentrations of cloxacillin
      were followed over 10.5 hr, and urine excretion of cloxacillin over 24 hr. The
      effect of the drugs on urinary excretion of protein indicators of glomerular
      (albumin, IgG) and tubular (protein HC) function was also studied. Total plasma
      clearance of cloxacillin was with placebo 219 +/- 51 (mean +/- S.D.), and with
      diclofenac 212 +/- 39 ml/min./1.73 m2 (ns); renal clearance was 97 +/- 21 and 96
      +/- 24 ml/min./1.73 m2, respectively (ns). The terminal t1/2 of cloxacillin was
      1.03 +/- 0.42 hr with placebo, and 1.12 +/- 0.37 with diclofenac (ns). The mean
      ratio of AUC0-infinity's (cloxacillin plus diclofenac/cloxacillin plus placebo)
      was 1.03 (90% CI: 0.99, 1.08). Urinary excretion of the proteins was low and was
      not increased by cloxacillin or diclofenac. In healthy volunteers, 60 years or
      older, diclofenac does not alter cloxacillin pharmacokinetics, and neither
      cloxacillin nor diclofenac in single intravenous doses cause renal dysfunction.

PMID- 9258982
TI  - Effect of time interval between food and drug ingestion on the absorption of
      oxybutynin from a controlled-release tablet.
AB  - The effect of time interval between food and drug ingestion on the
      bioavailability of oxybutynin was investigated in a randomized, three-phase cross
      over study in 31 healthy volunteers. The serum concentrations of oxybutynin and
      the metabolite, N-desethyloxybutynin were measured up to 48 hr after ingestion of
      a controlled-release 10 mg oxybutynin tablet either in fasting state, 2 hr after
      breakfast or 1 hr before. The Cmax of both oxybutynin (P < 0.0001) and N
      desethyloxybutynin (P < 0.0001) and the AUC0-1 of N-desethyloxybutynin (P < 0.05)
      were significantly larger when oxybutynin was ingested 2 hr after breakfast, than
      during the fasting, but the AUC0-1 of oxybutynin remained unchanged. Breakfast
      ingested 1 hr after oxybutynin did not affect the pharmacokinetic parameters of
      oxybutynin or N-desethyloxybutynin. The saliva secretion rate decreased slightly
      more (P < 0.05), when oxybutynin was administered 2 hr after breakfast than
      during fasting. The effect of food ingestion on the serum concentrations of
      oxybutynin and N-desethyloxybutynin is expected to have minor clinical
      significance only. However, ingestion of the controlled-release tablet 1 hr
      before meal increases the likelihood of obtaining constant drug levels with lower
      peak concentrations during the dosage interval, and thus ingestion of the
      controlled-release tablet 0.5-1 hr before food may well improve tolerability and
      compliance in patients who suffer from adverse reactions.

PMID- 9258980
TI  - Cholecystokinin-B/gastrin receptor blockade suppresses the activity of rat
      stomach ECL cells.
AB  - Gastrin controls the histamine- and chromogranin A-producing enterochromaffin
      like (ECL) cells, the predominant endocrine cell population in the acid-producing
      part of the rat stomach. They are responsible for most of the circulating
      pancreastatin, a chromogranin A-derived peptide. The present study examines the
      ability of two potent and highly selective cholecystokinin-B/gastrin receptor
      antagonists, RP73870 and YM022, to incapacitate the ECL cells. The two
      antagonists were given by continuous subcutaneous infusion to otherwise untreated
      rats and to hypergastrinaemic rats treated with gastrin-17 (continuous
      subcutaneous infusion) or omeprazole (orally) for 7 days. Several parameters
      reflecting ECL cell activity were measured: The oxyntic mucosal histidine
      decarboxylase activity, the histamine concentration, the histidine decarboxylase
      mRNA and chromogranin A mRNA concentrations, and the serum pancreastatin
      concentration. In addition, the serum gastrin concentration was measured. RP73870
      and YM022 greatly lowered the oxyntic mucosal histidine decarboxylase activity
      and the histidine decarboxylase mRNA and chromogranin A mRNA concentrations, and
      also reduced the oxyntic mucosal histamine concentration and the serum
      pancreastatin concentration. Moreover, they raised the serum gastrin
      concentration. With respect to blockade of histidine decarboxylase activity, 1.0
      mumol.kg-1.hr-1 was an almost maximally effective dose for both RP73870 and
      YM022. The corresponding ID50 values were 0.04 and 0.05 mumol.kg-1.hr-1. RP73870
      and YM022 inhibited the hypergastrinaemia-evoked rise in all ECL-cell parameters.
      The results suggest that sustained cholecystokinin-B/gastrin receptor blockade
      causes lasting deactivation of the ECL cells.

PMID- 9258983
TI  - Comparison and in vivo relevance of two different in vitro head space metabolic
      systems: liver S9 and liver slices.
AB  - In vitro systems of high biological organization, e.g. containing intact
      hepatocytes, have been considered as more reliable for metabolic studies and in
      vivo predictions of toxicokinetics than subcellular systems. For this reason, the
      kinetics and metabolism of low-molecular-weight volatile chemicals, i.e. head
      space elimination of substrate and formation of metabolites, were compared in
      liver S9 and in liver slices. Two substrates, toluene and n-hexane, were used as
      they represent differences in metabolic pathways and physical-chemical
      properties. The two systems responded similarly to diethyldithiocarbamate
      inhibition and acetone inhibition/induction of cytochrome P-450 mediated
      metabolism. In contrast to liver S9, liver slices did not respond adequately to
      phenobarbital induction raising the question of substrate availability for P-450
      enzymes in liver slices. Liver slices appeared to be superior to liver S9 when
      specific metabolic pathways involving phase II enzymes were investigated.
      However, liver S9 seemed to be at least as good as liver slices for estimation of
      total metabolic rate constants (Km, Vmax) as a basis for in vivo predictions. As
      the head space liver S9 system is faster and easier to operate than liver slices,
      it is a promising screening tool for the metabolism of volatile compounds and
      metabolic interactions.

PMID- 9258984
TI  - Increase of bone mass and mechanical strength in rats after treatment with a
      novel bisphosphonate, YM175, for two years.
AB  - We have evaluated the relationship between bone mass and mechanical properties of
      bone from male and female rats treated with YM175, a novel bisphosphonate, for
      104 weeks. YM175 [disodium (cycloheptylamino) methylenediphosphonate monohydrate]
      was given via the drinking water at a concentration of 0, 0.005, 0.015, 0.05, or
      0.15%. Since the mortality in the male 0.15% group exceeded the exclusion
      criteria (75%) at week 88, this-group was omitted from the study. Mean daily
      intake of YM175 was 2.2-22.1 mg/kg for males and 3.6-104 mg/kg for females. After
      the treatment, mechanical properties and ash weight of the humerus were
      determined. In males, 0.015 and 0.05% of YM175 (6.6-22.1 mg/kg) significantly
      increased failure load of the midshaft. In females, failure load and stiffness of
      the midshaft tended to be increased by YM175 (up to 104 mg/kg). Furthermore,
      ultimate compressive load at the humeral metaphysis treated with the highest dose
      of YM175 was 2- or 3.5-fold greater than that of untreated male or female
      control. Ash weight of the humerus was increased dose-dependently and was
      positively correlated with failure load of the midshaft. These findings indicate
      that treatment for 2 years with YM175 increased bone mass and mechanical strength
      without blocking bone mineralization.

PMID- 9258985
TI  - Accumulation of nicotine in human hair during long-term controlled exposure to a
      low concentration of nicotine vapour.
AB  - Hair from 5 subjects were exposed in dynamic exposure chambers to air nicotine
      vapour for 72 hr or 12 months at concentrations of 200 or 5 micrograms/m3,
      respectively. Nicotine in the chamber air and human hair was determined by GC/
      MS. A linear accumulation of nicotine in hair was found with time for all hairs
      during the long-term, low concentration exposure, with individual hair nicotine
      uptake rate constants ranging from 0.70 to 3.75 x 10(-3) m3/g x hr. The
      corresponding hair nicotine uptake rate constants during short-term, high
      concentration exposure, were significantly higher, ranging from 1.35 to 15.11 x
      10(-3) m3/g x hr, showing, however, a highly significant linear correlation with
      the individual long-term exposure rate constants, r2 = 0.9961. It is indicated
      that long-term hair nicotine uptake rate constants calculated from controlled
      exposure experiments with pure nicotine vapour are adequate for estimation of
      individual long-term hair accumulation of nicotine from environmental tobacco
      smoke even at variable and intermittent exposure. Although higher than the long
      term uptake rate constants, the short-term uptake rate constants seem well fitted
      for a differentiation between different types of hair in their ability to adsorb
      nicotine also during long-term exposures. The short-term uptake rate constants
      might also be useful parameters for establishing a reliable cut-off limit in the
      hair concentration of nicotine between smokers and non-smokers which otherwise
      seems to be overlapping.

PMID- 9258986
TI  - Prolonged treatment with the atypical antipsychotic agent remoxipride reduces
      extracellular glutamate levels in the striatum of freely moving rats.

PMID- 9258987
TI  - Cannabinoid-induced alterations in regional cerebral blood flow in the rat.
AB  - A specific receptor for cannabinoids has been characterized at the
      pharmacological, molecular, and neuroanatomical level. However, less is known of
      the functional localization in the brain for the behavioral and physiological
      actions of these drugs. We have examined the effects of delta 9
      tetrahydrocannabinol (THC) and its active metabolite 11-OH-THC on regional
      cerebral blood flow in the rat in order to determine functional CNS sites of
      action for the cannabinoids. Conscious rats were injected i.v. with one of four
      doses of THC (0.5, 1, 4, 16 mg/kg). 11-OH-THC (4 mg/kg), or vehicle 30 min prior
      to sacrifice. Regional cerebral blood flow was determined autoradiographically
      using the freely diffusible tracer method of Sakaruda et al. Changes in regional
      cerebral blood flow were observed in 16 of the 37 areas measured. Decreases in
      regional cerebral blood flow following THC were seen in such areas as the CA1
      region of the hippocampus, frontal and medial prefrontal cortex, the nucleus
      accumbens, and the claustrum. Thresholds for these effects ranged from 0.5 to 16
      mg/kg. Areas unaffected by THC include the medial septum, ventral tegmental area,
      caudate, temporal, parietal and occipital cortex, and cerebellum. These data
      indicate that THC and its active metabolite, 11-OH-THC, cause a heterogeneous
      alteration in the activity of specific CNS sites, many of which are involved in
      the characteristic behavioral actions of THC.

PMID- 9258988
TI  - Acute effects of LSD on rhesus monkey operant test battery performance.
AB  - The acute effects of LSD were assessed in rhesus macaques using behavior in
      several complex tasks designed to model aspects of time estimation, short-term
      memory and attention, motivation, learning, and color and position
      discrimination. The end points monitored included percent task completed,
      response rate, and accuracy. LSD (0.0003-0.03 mg/kg intravenously) significantly
      decreased percent task completed and accuracy in the time estimation task at
      doses < or = 0.003 mg/kg, but did not significantly affect response rate in this
      task at any dose tested. Accuracy in the short-term memory task was significantly
      decreased at the highest dose tested (0.03 mg/kg), but no other end points were
      affected in this task. Response rate was decreased in both the motivation and
      learning tasks at doses (0.01 and 0.003 mg/kg, respectively) lower than those
      affecting other end points. In the color and position discrimination task, only
      response rate was affected (0.01 and 0.03 mg/kg). These data demonstrate that in
      rhesus monkeys, performance of tasks believed to depend on aspects of time
      estimation and motivation are more sensitive to the acute disruptive effects of
      LSD than are tasks thought to model learning, short-term memory, and color and
      position discrimination.

PMID- 9258989
TI  - Safety of cotinine in humans: physiologic, subjective, and cognitive effects.
AB  - Preliminary data suggest that cotinine, the major metabolite of nicotine, may be
      behaviorally active. Studies involving the administration of cotinine at doses
      that produce high blood concentrations (in excess of those produced by cigarette
      smoking) may be of interest. This inpatient, 10-day human study examined the
      safety and the effects from several high doses of oral cotinine fumarate (40, 80,
      or 160 mg) or placebo in abstinent cigarette smokers. All subjects smoked
      cigarettes ad lib during the first 2 days of the study, then were required to be
      abstinent beginning on the third day. All subjects were given placebo on this day
      to wash out nicotine before the administration of cotinine. Subjects were
      subsequently randomly assigned in a double-blind manner to cotinine or placebo
      for the next 3 days to determine the safety profile of cotinine. All subjects
      were given placebo on the final 3 days to examine cotinine withdrawal symptoms.
      The results showed no significant physiologic, subjective, or performance effects
      across the various doses of cotinine and placebo. Furthermore, no cotinine
      withdrawal effects were observed. This study demonstrates that short-term
      administration of cotinine to humans at levels as high as 10 times that attained
      from cigarette smoking is safe with no observable acute or withdrawal effects
      from cotinine in this setting.

PMID- 9258990
TI  - Phenobarbital sensitivity in HAS and LAS rats before and after chronic
      administration of ethanol.
AB  - Rats selectively bred for high alcohol sensitivity (HAS) or low alcohol
      sensitivity (LAS) were tested for initial sensitivity to hypnotic doses of
      ethanol and a locomotor-altering dose of phenobarbital. Following 6 weeks of
      either a pair-fed control or 33% ethanol-derived calorie diet, animals were
      tested again for tolerance to ethanol and cross-tolerance to phenobarbital. HAS
      and LAS rats did not differ in baseline open field or Rotarod activity before
      chronic ethanol treatment. However, HAS rats were more sensitive to 50 mg/ kg
      phenobarbital relative to LAS rats. Both control- and ethanol-diet rats appeared
      to be less sensitive to phenobarbital after the 6-week treatment period. Chronic
      ethanol-exposed HAS and LAS rats demonstrated tolerance to ethanol and cross
      tolerance to phenobarbital, and in particular LAS rats were even more active in
      the open field following phenobarbital relative to controls. In summary,
      significant differences in response to phenobarbital were observed between HAS
      and LAS rats. These observations suggest that initial sensitivity and tolerance
      to ethanol are associated with differences in phenobarbital sensitivity and are
      influenced by similar genes.

PMID- 9258991
TI  - Reduced tolerance to certain pharmacological effects of ethanol after chronic
      administration in perinatally undernourished rats.
AB  - We have previously reported that recovered adult rats undernourished at perinatal
      age failed to develop tolerance to the anticonflict effect of ethanol after
      chronic ethanol administration (1 g/kg/day during 30 days) (4). To further study
      the extent of this finding, we examined the effect of a similar chronic ethanol
      treatment on the hypothermic and anticonvulsant effects of ethanol in perinatally
      deprived rats. Hypoalgesic activity was assessed in ethanol treated rats during
      15 days. After chronic ethanol treatment, a similar development of tolerance to
      the hypothermic effect of ethanol was observed in control and deprived rats.
      However, tolerance to the anticonvulsant and hypoalgesic effect of ethanol was
      significantly reduced in deprived as compared with control animals. Thus, early
      undernutrition differentially affects the development of tolerance elicited by
      chronic ethanol administration.

PMID- 9258992
TI  - Behavioral sensitization to cocaine in the absence of altered brain cocaine
      levels.
AB  - We conducted experiments investigating the role of altered cocaine distribution
      in behavioral sensitization. The first was designed to determine whether carry
      over from one injection to the next occurs after acute cocaine administration.
      Female, Sprague-Dawley rats were administered 5 mg/kg 3H-cocaine and 24 h later
      were challenged with either 5 mg/kg unlabeled cocaine or saline. Animals were
      sacrificed 15 min after drug administration. There was no difference between
      groups in cocaine levels in brain, liver, or plasma, thus indicating that carry
      over did not occur following acute cocaine administration. The second experiment
      was designed to determine whether bound cocaine could be released following acute
      or multiple dose cocaine administration. In the acute dose study, animals were
      administered either 20 mg/kg cocaine or saline, challenged 24 h later with 5
      mg/kg 3H-cocaine, and sacrificed 5 min after drug administration. Animals with
      previous cocaine experience exhibited a significant increase in the number of
      rearings. The groups did not differ in brain or plasma cocaine levels. In the
      multiple dose study, animals were injected daily for 4 days with 20 mg/kg cocaine
      or saline, challenged with 5 mg/kg 3H-cocaine on day 5, and sacrificed 10 min
      after drug administration. Animals with previous cocaine experience exhibited
      significantly greater locomotor activity and number of rearings. There was no
      difference between groups in cocaine levels in various brain regions, plasma, or
      liver. Brain cocaine content in various regions was significantly correlated,
      though heterogeneously distributed within the various regions. The highest
      cocaine levels were found in hippocampus, striatum, thalamus/hypothalamus, and
      cortex. These results provide further evidence that behavioral sensitization is
      not the result of cocaine redistribution following repeated administration.

PMID- 9258993
TI  - Effect of adenosine receptor agonists and antagonists on the expression of opiate
      withdrawal in rats.
AB  - The effects of the selective A1 adenosine receptor agonist N6
      cyclopentyladenosine (CPA) and the selective A2a agonist 2-[p-(2
      carboxethyl)phenylethyl-ethylamino]-5'-ethylcarboxamidoade nosine (CGS 21680)
      (each at 0.03, 0.1 and 0.3 mg/kg, SC) as well as the selective A1 adenosine
      receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), non-selective
      antagonists 3-isobutyl-1-methylxanthine (IBMX), aminophylline, 3,7-dimethyl-1
      propargyl-xanthine (DMPX) and 8(p-sulfophenyl)-theophylline (8-SPT) were
      investigated (each at 5, 10 and 30 mg/kg, SC) for their ability to alter the
      naloxone-precipitated opiate withdrawal syndrome in morphine-dependent rats.
      Effects of CPA and CGS 21680 on opiate withdrawal in the presence of
      aminophylline were also investigated. Both CPA and CGS 21680, caused a
      significant reduction in the incidence of body shakes, teeth chatter and paw
      shakes and decreased the amount of faecal matter produced. DPCPX, IBMX, DMPX, 8
      SPT and aminophylline significantly increased the incidence of jumps and
      decreased the amount of faecal matter produced. The incidence of body shakes was
      significantly increased by DMPX, 8-SPT and IBMX. Neither CPA nor CGS 21680 were
      able to reverse the significant increase in the incidence of jumps caused by
      aminophylline. These data suggest that there is a role for endogenous adenosine
      in the modulation of the opiate abstinence syndrome and both A1 and A2a adenosine
      receptors are involved in this phenomenon.

PMID- 9258994
TI  - A role for D2, but not D1, dopamine receptors in the response-reinstating effects
      of food reinforcement.
AB  - Although the reinforcing properties of food are reduced in the presence of
      dopamine antagonist drugs, controversy exists about the relative roles of D1 vs
      D2 receptor subtypes in the actions of these drugs. The current experiment
      compared the effects of raclopride (a selective D2 receptor antagonist) and SCH
      39166 (a selective D1 receptor antagonist) in the response-reinstating effects of
      food reinforcement. Hungry rats were trained to run a straight-alley for food
      reinforcement during single daily trials. The operant was then extinguished
      during consecutive daily non-reinforced trials. Subjects were then injected with
      one of four doses of raclopride (0.0, 1.0, 0.5, and 0.25 mg/kg, i.p.) or SCH
      39166 (0.0, 1.0, 0.5, and 0.1 mg/kg i.p.) 30 min prior to a single reinforced
      treatment trial. Twenty-four h later, a test trial was conducted in an unbaited
      runway. The single reinforced trial in the midst of extinction was observed to
      reinstate operant runway performance. Raclopride, but not SCH 39166, dose
      dependently attenuated this reinstatement. Motor control groups ruled out the
      possibility that these results were due to differential residual motor effects of
      the drugs. Results suggest that D2, but not D1, dopamine receptors, are involved
      in the response-reinstating properties of food reinforcement.

PMID- 9258995
TI  - Ketanserin effects on rat behavioral responses: modifications by the estrous
      cycle, ovariectomy and estradiol replacement.
AB  - The present investigation was designed to explore the influence of estrous cycle
      phase, ovariectomy, and estradiol replacement on the behavioral effects of the 5
      HT2 receptor antagonist, ketanserin. The parameters under investigation were
      ketanserin-influenced acquisition of conditioning avoidance responses (CARs), and
      the performance of some spontaneous motor behaviors. Ketanserin (KET 3 mg/kg)
      injected subcutaneously 30 min before testing improved active conditioned
      avoidance in intact female rats at estrus, and in ovariectomized (OVX) rats with
      estradiol replacement. Furthermore, KET impaired performance in female rats at
      diestrus and after ovariectomy. In male rats, which were included in this study
      in order to compare their behavioral responses with those exhibited by female
      rats, KET administration enhanced acquisition of CARs. These results provide
      behavioral evidence for the hypothesis that central serotonergic activity is a
      function of the hormonal status of the animal. An additional segment of the
      present study focussed on motoric behaviors. Spontaneous motor activity, number
      of rears, and time spent in grooming behavior were significantly increased by KET
      in all groups studied. In contrast, blockade of 5-HT2 receptors failed to induce
      significant changes in the number of head shakes. Relationships between ovarian
      hormones and the central serotonergic system are discussed.

PMID- 9258996
TI  - Effect of NMDA antagonists on rapid tolerance to ethanol under two different
      testing paradigms.
AB  - We have recently reported that pretreatment with NMDA receptor antagonists [(+)MK
      801 and ketamine] inhibited the development of rapid tolerance to ethanol
      hypothermia and motor-impairment on day 2 in animals receiving ethanol on day 1,
      compared to the control group pretreated with saline. In these studies rats were
      tested at 30, 60, 90 and 120 min after ethanol on both day 1 and 2. In the
      present report we compared the development of rapid tolerance under 2 different
      conditions: (1) in groups of rats that were tested on the tilt-plane at all test
      times (Testing or Intoxicated Practice group), (2) in groups of rats that were
      not tested on the tilt-plane but were handled at all test times on day 1 (dummy
      testing). Rats were pretreated with ethanol or saline on day 1 and tested with
      ethanol on day 2 in all the above studies. Both testing (intoxicated practice)
      and dummy testing of animals on day 1 after pretreatment with ethanol produced
      rapid tolerance to ethanol on day 2. However, (+)MK-801 or ketamine pretreatment,
      which blocked rapid tolerance in the intoxicated practice testing paradigm,
      failed to block rapid tolerance in the dummy testing paradigm. Similar results
      were obtained for rapid tolerance and for the effect of ketamine in the
      hypothermia experiment. These findings suggest that NMDA antagonists block rapid
      tolerance in the intoxicated testing paradigm but not in the dummy testing
      paradigm. However, whether the two types of rapid tolerance tested in the present
      experiments are indeed different or interrelated remains to be further
      investigated.

PMID- 9258998
TI  - The role of muscarinic cholinergic receptors in the discriminative stimulus
      properties of clozapine in rats.
AB  - The present study examined the role of muscarinic receptors in the discriminative
      stimulus properties of clozapine. One group of rats was trained to discriminate
      the atypical antipsychotic clozapine (CLZ, 5.0 mg/kg, i.p.) from vehicle in a two
      lever drug discrimination procedure, and a second group of rats was trained to
      discriminate the muscarinic cholinergic antagonist scopolamine (SCP, 0.125 mg/kg,
      i.p.) from saline. Complete cross-generalization was obtained for SCP in the CLZ
      trained rats and for CLZ in the SCP-trained rats. The M1 muscarinic antagonist
      trihexyphenidyl substituted completely for both CLZ and SCP; however, the M2
      antagonist BIBN 99 failed to substitute for either CLZ or SCP. In other
      substitution tests, the tricyclic antidepressant amitriptyline, the antihistamine
      promethazine, and cyproheptadine (5-hydroxytryptamine [5-HT]2A/5-HT2C, histamine,
      and muscarinic antagonist) substituted completely for CLZ and SCP. The
      tetracyclic antidepressant mianserin substituted completely in the CLZ-trained
      rats, but did not substitute for SCP. Compounds that produced partial
      substitution included the tricyclic antidepressant imipramine, the anxiolytic
      chlordiazepoxide, and the antipsychotic thioridazine. Other compounds tested only
      in the CLZ-trained rats that failed to produce reliable CLZ-appropriate
      responding included N-methyl-D-aspartic acid (NMDA, selective agonist for
      glutamate receptors), metergoline (5-HT2A/5-HT2C antagonist), propranolol (beta
      noradrenergic antagonist), and phentolamine (alpha noradrenergic antagonist). All
      of the compounds that produced CLZ-appropriate responding (except for mianserin)
      display high binding affinities for muscarinic cholinergic receptors. The results
      of the present study demonstrated that muscarinic receptors (especially M1) play
      an important role in the mediation of the discriminative stimulus properties of
      CLZ in rats, and provide additional support for the importance of CLZ's
      anticholinergic properties as part of it's unique profile as an atypical
      antipsychotic.

PMID- 9258997
TI  - Role of angiotensin in the dipsogenic effect of bradykinin in rats.
AB  - We have previously shown that peripheral administration of bradykinin (BK)
      induces water intake in rats acutely pretreated with captopril, a kininase II
      inhibitor. We now show that BK-induced drinking is also observed in rats treated
      chronically with dietary captopril, and that this is reversed by Hoe 140, a BK
      receptor antagonist. Both acute and chronic captopril in combination with BK
      caused a large increase in plasma renin activity. Fos-like immunoreactivity (Fos
      in used as a marker of cellular activation) was induced by BK + captopril in
      regions of the brain previously associated with action of angiotensin (Ang) II,
      including the circumventricular organs and the magnocellular hypothalamic nuclei.
      However, while water intake induced by peripheral administration of Ang I was
      potentiated by acute administration of captopril, it was suppressed by chronic
      captopril treatment. Fos-IR induced in brain by Ang I was not markedly affected
      by either acute or chronic treatment with captopril. The simultaneous occurrence
      of potentiated drinking to BK and inhibited drinking to Ang I following chronic
      treatment with captopril suggest that different mechanisms of action are
      involved. In order to further examine this possibility, rats were given lesions
      of the anterodorsal third ventricle region. Lesions that completely abolished the
      water intake following administration of Ang II only partly attenuated water
      intake induced by BK + captopril. Further, Fos-IR induced by BK + captopril was
      only partly (31%) reduced in the supraoptic and paraventricular nuclei of
      lesioned rats compared with sham operated controls. We suggest that at least two
      mechanisms, one Ang-related, underlie drinking after BK+captopril.

PMID- 9258999
TI  - Male/female differences in drug-induced emesis and motion sickness in Suncus
      murinus.
AB  - In order to elucidate possible male/female differences in emesis, the effects of
      various emetogenic drugs (cisplatin, copper sulfate, veratrine, nicotine,
      serotonin) and motion stimulus were compared between male and female Suncus
      murinus. Cisplatin (IP), nicotine (SC), veratrine (SC) and copper sulfate (PO)
      induced dose-dependent emesis in either sex, and there was no apparent difference
      in estimated ED50 values. However, male animals tended to be more susceptible to
      serotonin-induced emesis. The ID50 values for tropisetron, a 5-HT3 receptor
      antagonist, to block serotonin-induced emesis were also similar between male and
      female animals. However, tropisetron was less effective against cisplatin-induced
      emesis in females. Therefore, cisplatin may release more serotonin to induce
      emesis in females. Reciprocal shaking (horizontal oscillation 40 mm, frequency
      0.5 to 2.0 Hz, duration 5 min) induced more frequent emesis in male animals, and
      the latency to the first vomit was shorter in males than in females. These
      results suggest that there is substantial sex-dependent difference in the emetic
      responses and male animals are in general more susceptible. These results are
      discussed in the light of similar studies in man.

PMID- 9259000
TI  - Responses to propofol in relation to GABA functionality of discrete parts of the
      brain of rats.
AB  - Genetically-determined regional differences in the GABA-ergic make-up of the
      brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and
      apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic
      general anesthetic. This study compared the responses to propofol in APO-SUS and
      APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular
      contractions and oral movements, but a lower incidence of grooming, in APO-SUS
      rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the
      behavior marked by both full absence of purposeful movements and by complete loss
      of righting reflexes, after propofol did not differ between the two lines. APO
      SUS rats had less variation of the heart rates and greater variations of
      diastolic arterial pressures in response to electrical stimulation than the APO
      UNSUS rats, and these variations were reduced by increasing doses of propofol.
      Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol
      caused a biphasic change in intra-arterial pressures and had the greatest effect
      in APO-SUS rats. Differences in cerebral GABA transmission, especially in the
      striato-nigro-collicular pathway, did not give rise to differences in the effect
      of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these
      differences in GABA transmission were accompanied by line-specific differences in
      effect of propofol on certain behavioral and cardiovascular parameters.

PMID- 9259001
TI  - Assessment of the MDA and MDMA optical isomers in a stimulant-hallucinogen
      discrimination.
AB  - The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and
      3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants
      and hallucinogens in drug discrimination investigations. The stereoisomers of
      these compounds, in particular those of MDA, appear to produce differential
      effects. Previous studies have demonstrated that animals trained to discriminate
      amphetamine from vehicle generalize to the S(+)-isomers but not the R(-)-isomers
      of MDA and MDMA while animals trained to discriminate LSD from saline generalize
      to R(-)-MDA and neither isomer of MDMA. However, animals trained to discriminate
      mescaline from vehicle generalize to both stereoisomers of these
      phenylisopropylamine derivatives. The present study consisted of two experiments
      in which a three-choice drug discrimination procedure was employed to compare the
      stereoisomers of MDA and MDMA to both amphetamine and either mescaline
      (experiment one) or LSD (experiment two). Sixteen male Sprague-Dawley rats were
      trained to discriminate S(+)-amphetamine (1.0 mg/kg) and mescaline (12.5 mg/kg)
      and eight rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and LSD
      (0.08 mg/kg) from saline in three-choice, food reinforced drug discrimination
      procedures. Substitution tests were administered with the isomers of MDA and
      MDMA. In the second experiment, substitution tests were also administered with
      lower doses of each training compound and with the stimulant cocaine and the
      hallucinogen 2,5-dimethoxy-4-methylphenylisopropylamine (DOM). In both
      experiments, all of the isomers produced very few responses on the S(+)
      amphetamine lever. In the first experiment, R(-)-MDA and R(-)-MDMA produced
      nearly complete substitution for mescaline. The results of the second experiment
      revealed partial substitution for LSD with both isomers of MDMA and S(+)-MDA, and
      nearly complete substitution with R(-)MDA for LSD. The present findings do not
      support previous reports that S(+)-MDMA and S(+)-MDMA substitute for S(+)
      amphetamine. The three-lever drug discrimination procedure may provide a more
      sensitive behavioral assay in which to examine the discriminative stimulus
      effects of drugs with compound stimulus properties.

PMID- 9259004
TI  - Assessment of the role of oxytocin receptors in phenylpropanolamine-induced
      anorexia in rats.
AB  - The anorexic effects of phenylpropanolamine (PPA) have been attributed to
      activation by PPA of alpha 1-adrenoceptors within rat hypothalamic
      paraventricular nucleus (PVN). The PVN, however, is a nexus for a number of
      ascending and descending fibers systems that release transmitters and modulators
      known to inhibit appetite. The focus of the present study was to assess the
      possibility that oxytocin activity might play a role in the anorexic action of
      PPA. The present study therefore examined the effects of systemic administration
      of the oxytocin antagonist L-366,948 on PPA-induced anorexia. Adult male rats (n
      = 10 per group) were pretreated (i.p.) with either 0, 1, or 2 mg/kg L-366,948 15
      min prior to treatment injections (i.p.) of either 0, 5, 10 and 15 mg/kg PPA.
      Food and water intakes were recorded for a 30 min period (1600 h) starting 30 min
      after the treatment injection. Rats pretreated with vehicle and then treated with
      PPA exhibited a dose-dependent suppression of feeding with a maximal effect
      evident at 15 mg/kg PPA. Pretreatment with 1 or 2 mg/kg L-366,948 alone did not
      alter feeding nor did these doses alter the anorexia induced by PPA. These
      results suggest that direct or indirect oxytocin activity is not a factor in the
      anorexic action of PPA, a finding that further strengthens the notion that PPA
      inhibits food intake via activation of alpha 1-adrenoceptors.

PMID- 9259003
TI  - Ethanol preference, metabolism, blood pressure, and conditioned taste aversion in
      experimental cholestasis.
AB  - The effect of a ligation of the common bile duct (BDL) on the chronic free
      selection intake of ethanol was investigated. Rats were given a choice between
      water and a solution of either 6% (v/v) ethanol, 0.06% (w/v) sodium saccharin, or
      a mixture of both ethanol and saccharin. In different experiments, solutions were
      first presented either 3 weeks before surgery, about the time of surgery, or 2
      weeks after surgery. Reductions in ethanol or saccharin intake were observed in
      BDL rats whenever the solutions were first presented either 3 weeks before or
      shortly after the surgery. No differences attributable to BDL were seen when
      ethanol solutions were first presented 2 weeks after surgery. The contingent
      nature of the effect suggests that the reduction results from a conditioned taste
      aversion rather than from differences in ethanol metabolism, sensitivity, or
      neurohormones such as angiotensin. The findings urge caution in the monitoring of
      the dietary habits of patients with a rapidly developing biliary obstruction.

PMID- 9259002
TI  - Effect of third ventricle administration of L-694,247, a selective 5-HT1D
      receptor agonist, on water intake in rats.
AB  - L-694,247, a selective 5-HT1D receptor agonist, injected directly into the third
      ventricle (2.5, 5.0, and 10.0 micrograms/rat) of dehydrated rats induced a dose
      dependent partial blockade of water intake. Injected in this way, the compound
      abolishes drinking behavior induced by third ventricle administration of
      carbachol (2 micrograms/rat), angiotensin II (5 ng/rat), and isoproterenol (40
      micrograms/rat). In addition, intraventricular injections of L-694,247 did not
      modify water intake in normohydrated rats. The effects of L-694,247 are due to a
      specific interaction with 5-HT1D receptors, because its inhibitory effect on
      water intake in dehydrated rats is blocked by the previous administration of a 5
      HT1D antagonist, GR 127935 (5 micrograms/rat), directly into the third ventricle.
      It is concluded that central 5-HT1D receptor activation disrupts the functional
      integrity of central pathways related to drinking behavior.

PMID- 9259005
TI  - Antagonism of morphine-like discriminative effects by beta-funaltrexamine.
AB  - beta-Funaltrexamine (beta-FNA), an irreversible antagonist at the mu-opioid
      receptor, was administered intracisternally to rats discriminating between
      subcutaneous injections of saline and 3.0 mg/kg of morphine in order to reduce
      the size of the receptor reserve. beta-FNA alone (10 micrograms) occasioned
      substantial morphine-appropriate responding for at least 6 h but mainly saline
      appropriate responding 24 h after administration, the pretreatment interval for
      most experiments. beta-FNA (3.0-30 micrograms) dose-dependently shifted to the
      right stimulus-generalization curves for morphine and fentanyl; 10 micrograms
      also shifted to the right the curves for meperidine and buprenorphine. In all
      cases, antagonism was fully surmounted by higher doses of the agonist, even after
      inactivation of more than 75% of mu-opioid receptors. This antagonist effect of
      beta-FNA is smaller than that reported previously in tests of analgesia,
      suggesting that the receptor reserve for the discriminative effects of morphine
      like drugs is larger than the receptor reserve for their analgesic effects. beta
      FNA produced larger rightward displacements of the morphine and buprenorphine
      curves than of the fentanyl curve and inactivated a larger fraction of the
      receptors acted upon by those drugs compared to fentanyl. Results with meperidine
      were intermediate. This suggests that the receptor population mediating morphine
      like discriminative effects of fentanyl is not identical to the receptor
      population mediating these effects of morphine and buprenorphine.

PMID- 9259006
TI  - Precipitated morphine withdrawal induces a conditioned aversion in the preweaning
      rat.
AB  - Opiate abstinence in the adult of many species, including humans, alters
      autonomic function and motor behavior, and induces a negative affective state.
      The neurobehavioral bases of each consequence of opiate withdrawal differs.
      Little attention has been paid to the issue of drug withdrawal in infants,
      although it is a common consequence of the maternal use of illegal and legal
      drugs. Infant rats as young as 7 days of age that experience opiate withdrawal
      show an abstinence syndrome consisting of developmentally appropriate behaviors
      that differ from those of the adult rat, including fewer autonomic signs. Unlike
      the adult, there are no data in the infant on whether or not opiate withdrawal
      induces a negative affective state. We treated infant rats twice daily for seven
      days with either morphine or saline. Pups were injected with naltrexone or saline
      and exposed to a novel odor. After conditioning, pups were given the option of
      spending time with the conditioned odor or in a neutral environment. Fourteen day
      old pups, but not 7 day old animals, chronically treated for 7 days with morphine
      and conditioned with naltrexone, showed a significant avoidance of the
      conditioned odor. This suggests that a conditioned aversion had formed, a result
      similar to that shown for adult animals.

PMID- 9259007
TI  - Activating the posttraumatic cholinergic system for the treatment of cognitive
      impairment following traumatic brain injury.
AB  - Cognitive impairment after traumatic brain injury (TBI) is correlated with
      decreased cholinergic markers of neuronal viability. The purpose of this
      experiment was to test the hypothesis that pharmacological activation of the
      muscarinic cholinergic system during the recovery period after TBI will improve
      cognitive performance. LU 25-109-T is a partial muscarinic M1 agonist that also
      acts as an antagonist at presynaptic M2 autoreceptors (thus increasing ACh
      release). Injured rats were injected subcutaneously daily for 15 days with either
      0.0, 3.6, or 15 mumol/kg of LU 25-109-T beginning 24 h after a receiving a
      moderate (2.1 +/- 0.1 atm) level of central fluid percussion brain injury.
      Cognitive performance was assessed on days 11-15 postinjury in a Morris water
      maze (MWM). Injured rats treated with 15 mumol/kg, but not those treated with 3.6
      mumol/kg, showed a significant improvement (p < 0.01) in MWM performance as
      compared with injured vehicle-treated rats. This result supports the hypotheses
      that a decrease in posttraumatic cholinergic neurotransmission contributes to TBI
      induced cognitive deficits and that increasing cholinergic tone during the
      recovery period following TBI will improve cognitive performance.

PMID- 9259008
TI  - Reversal of scopolamine-induced deficits in navigational memory performance by
      the seed oil of Celastrus paniculatus.
AB  - Celastrus paniculatus (CP), a medicinal plant from India has been reputed to be
      useful as a pharmaceutical aid for learning and memory. We investigated the
      effects of the seed oil of CP on the 6 day performance of young adult rats in a
      navigational memory task-the Morris water maze. Chronic oral (gavage) daily
      treatment with CP. (50, 200, or 400 mg/kg) for 14 days completely reversed the
      scopolamine (0.5 mg/kg)-induced task performance deficit. On the other hand,
      acute treatment (single injection prior to scopolamine treatment) with CP (200
      mg/kg) did not significantly reverse the scopolamine-induced impairment in maze
      performance. Alone, CP produced a slight, but significant improvement in maze
      performance on the first day of testing. Acute treatment or chronic 14 day
      treatment with CP resulted in no significant alteration in normal locomotor
      activity in an open field. Moreover, CP did not alter the scopolamine-induced
      increases in locomotor activity. Chronic treatment with CP did not alter brain
      acetylcholinesterase levels and no signs of cholinergic overstimulation were ever
      noted during or after treatment. Thus, the seed oil of CP, when administered
      chronically, selectively reversed the impairment in spatial memory produced by
      acute central muscarinic receptor blockade, supporting the possibility that one
      or more constituents of the oil may offer cognitive enhancing properties. The
      neural mechanism underlying the reversal of scopolamine's mnemonic effects by CP
      is not yet known, but it is not related to an anticholinesterase-like action.

PMID- 9259009
TI  - Role of morphine glucuronide metabolites in morphine dependence in the rat.
AB  - Concentrations of morphine and its 3- and 6-glucuronide metabolites (M3G and M6G)
      in plasma, brain, and urine of rats exposed to morphine for either 24 or 48 h
      were measured using high-performance liquid chromatography. In another group of
      morphine-treated rats, the intensity of naloxone-precipitated withdrawal
      behaviours was monitored at 24 and 48 h. The behavioural effects of M3G in opiate
      naive and opiate-dependent rats were also investigated. Morphine was present in
      plasma, urine, and brain at 24 and 48 h, whereas M3G was detected in plasma and
      urine only. M6G was not present in detectable quantities in either plasma, urine,
      or brain. Although plasma concentrations of M3G were similar in both time groups,
      rats treated for 48 h had significantly larger quantities of M3G in their urine
      than did the other treatment groups. The incidence of withdrawal behaviour was
      significantly higher in animals exposed to morphine for 48 h than in those with
      only 24 h of exposure, M3G had no behavioural effects in the opiate-naive rats
      and did not precipitate an opiate-abstinence syndrome in morphine-dependent rats.
      From these results, it was concluded that although M3G is the major product
      formed by morphine breakdown in rats, it is unlikely that it is involved in the
      development of morphine dependence in this species.

PMID- 9259010
TI  - Sex differences in ibogaine antagonism of morphine-induced locomotor activity and
      in ibogaine brain levels and metabolism.
AB  - The present study demonstrates that the putative antiaddictive agent ibogaine
      produces more robust behavioral effects in female than in male rats and that
      these behavioral differences correlate with higher levels of ibogaine in the
      brain and plasma of female rats. There were no differences in basal locomotor
      activity between the sexes, and the response of rats to ibogaine differed between
      the sexes even in the absence of morphine. Five h after receiving ibogaine (40
      mg/kg, i.p.). antagonism of morphine-induced locomotor activity was evident in
      female but not in male rats. Either 19 h after administration of ibogaine (10-60
      mg/kg, i.p.), or one h after administration of noribogaine (5-40 mg/kg, i.p.), a
      suspected metabolite, antagonism of morphine was significantly greater in female
      than in male rats. Brain and plasma levels of ibogaine (1 h) and noribogaine (5
      h), measured by gas chromatography-mass spectrometry, were greater in females as
      compared with males receiving the same dose of ibogaine. Levels of both ibogaine
      and noribogaine were substantially lower at 19 h than at earlier times after
      ibogaine administration, contrary to a previous study in humans. For both sexes,
      subcutaneous administration of ibogaine (40 mg/kg, i.p., 19 h) produced greater
      antagonism of morphine-induced locomotor activity than did a comparable
      intraperitoneal injection, consistent with previous studies from this laboratory
      demonstrating that the former route of administration produces higher levels of
      ibogaine in the brain. These data show that there are sex differences in the
      effects of ibogaine and that this may be due to decreased bioavailability of
      ibogaine in males as compared to females.

PMID- 9259011
TI  - Risk assessment behaviour: evaluation of utility in the study of 5-HT-related
      drugs in the rat elevated plus-maze test.
AB  - The present study compared the effects of a wide range of 5-hydroxytryptamine (5
      HT)-modulating and potential anxiolytic agents in the rat elevated plus-maze
      using spatiotemporal (i.e., open arm time and entries) and ethologically derived
      measures (i.e., risk assessment activities and directed exploration). The drugs
      used were 5-HT1A receptor partial (buspirone and ipsapirone) and full (8-OH-DPAT
      and flesinoxan) agonists, mixed 5-HT2A/2C receptor antagonists (ritanserin,
      ketanserin, mianserin, and pirenperone), selective 5-HT3 receptor antagonists
      (ICS 205-930, MDL 72222, ondansetron, and (RS)-zacopride), and selective
      (fluoxetine, fluvoxamine, and zimelidine) and nonselective (imipramine) 5-HT
      reuptake inhibitors. Only buspirone and mianserin produced effects indicative of
      an anxiolytic-like action on the spatiotemporal measures. However, all 5-HT1A
      receptor ligands, as well as mianserin, ketanserin, ondansetron, and zacopride,
      decreased the number of aborted attempts at entry into open arms (risk
      assessment). In addition, buspirone, mianserin, and zacopride increased head
      dipping (directed exploration). Among the 5-HT reuptake inhibitors, zimelidine
      reduced head-dipping and total entries. The present findings demonstrate that
      risk assessment responses are sensitive to the action of 5-HT1A receptor ligands,
      but their modulation by drugs targetting 5-HT2A, 5-HT2C, and 5-HT3 receptors was
      not convincingly established.

PMID- 9259012
TI  - Conditioned grooming induced by the dopamine D1-like receptor agonist SKF 38393
      in rats.
AB  - Stimulation of dopamine D1-like receptors reliably increases grooming in rats and
      mice. The study examined whether the grooming response elicited by the
      prototypical D1-like agonist SKF 38393 (8 mg/kg s.c.) could be conditioned to the
      specific environment in which it occurred. Rats in one group (Paired) received
      SKF 38393 and rats in another group (Unpaired) received saline in observation
      boxes outside of their housing room; the rats were then scored for duration and
      frequency of grooming bouts over 25 min. The ordering of injections was reversed
      the next day in the rats, housing room. The procedure was repeated twice, with at
      least one intervening drug-free day, to give three conditioning trials. The D1
      like agonist significantly increased grooming on each of the three conditioning
      trials, without obvious tolerance or sensitization, and the effect tended to
      persist for the duration of each trial. On the test trial for conditioned
      grooming, mean grooming duration was significantly greater in the Paired than the
      Unpaired group, suggesting that SKF 38393-induced grooming had been conditioned
      to the test environment. This is the first time that drug-elicited grooming has
      been conditioned to environmental cues.

PMID- 9259013
TI  - 5-HT1A agonists induce central cholinergic antinociception.
AB  - The antinociceptive effects of the 5-HT1A agonists buspirone [3 mg/kg
      intraperitoneally (i.p.)], gepirone (3-6 mg/kg i.p.), and 8-OH-DPAT [3-5 mg/kg
      i.p.; 1-3 micrograms per mouse intracerebroventricularly (i.c.v.)] were examined
      in mice by using the hot-plate (thermal stimulus) and abdominal constriction
      (chemical stimulus) tests. Buspirone, gepirone, and 8-OH-DPAT produced
      significant antinociception, which was prevented by atropine (5 mg/kg i.p.), the
      ACh depletor hemicholinium-3 (1 microgram per mouse i.c.v.), and the 5-HT1A
      antagonist NAN 190 (0.5 microgram per mouse i.c.v.), but not by naloxone (1 mg/kg
      i.p.), the GABAB antagonist CGP 35348 (100 mg/kg i.p.), and pertussis toxin (0.25
      microgram per mouse i.c.v.). NAN 190 which totally antagonized buspirone,
      gepirone, and 8-OH-DPAT antinociception, did not modify the analgesic effect of
      morphine (5 mg/kg subcutaneously). In the antinociceptive dose range, none of the
      5HT1A agonists impaired mouse performance evaluated by rota-rod and hole board
      tests. On the basis of these data, it can be postulated that buspirone, gepirone,
      and 8-OH-DPAT exert an antinociceptive effect mediated by a central amplification
      of cholinergic transmission.

PMID- 9259014
TI  - Bidirectional effects of dopamine D2 receptor antagonists on responding for a
      conditioned reinforcer.
AB  - In general, the administration of dopamine (DA) antagonists has been shown to
      result in the attenuation of reward processes. Recently, however, it has been
      suggested that low doses of DA antagonists can enhance the incentive value of a
      primary reinforcer. The present study examined the effect of DA receptor
      antagonists on responding for a conditioned stimulus (CS) and compared their
      effects to that produced by d-amphetamine. For 12 days, food-deprived rats were
      trained to associate a CS with a food reward. In the test phase, the CS was
      presented following a response on one of two levers (CR), whereas responding on
      the other lever (NCR) had no consequence. Low doses of d-amphetamine (0.5 mg/kg),
      sulpiride (4 mg/kg), pimozide (0.025 mg/kg), and raclopride (0.05 mg/kg)
      selectively enhanced responding on CR. A low dose of haloperidol (0.01 mg/kg) led
      to a nonspecific increase in lever responding. Treatment with larger doses of
      these compounds as well as with the D1 antagonist SCH23390 attenuated responding
      on CR. Both CR and NCR responding were reduced following administration of higher
      doses of d-amphetamine. Results indicate that responding for a conditioned
      reinforcer is potentiated following administration of low doses of D2 receptor
      antagonists, suggesting that D2 receptor blockade can facilitate incentive
      motivation.

PMID- 9259016
TI  - No major differences in locomotor responses to dexamphetamine in high and low
      responders to novelty: a study in Wistar rats.
AB  - The aim of the study was to compare locomotor responses to acute and sub-chronic
      dexamphetamine in two distinct types of Wistar rats, namely the Nijmegen high
      responders to novelty (HR) and Nijmegen low responders to novelty (LR). HR and LR
      were chosen because they differ in neurochemical processes relevant to the
      control of the locomotor effects of dexamphetamine, such as the dopaminergic and
      adrenergic activity in the nucleus accumbens. In experiment 1, a dexamphetamine
      dose-response curve (0.0-2.0 mg/kg/i.p.) was established using standard activity
      boxes. The dose-response curve slightly, but significantly, differed between HR
      and LR: especially the increase elicited by 1.5 mg/kg dexamphetamine was
      significantly greater in HR than in LR. In experiment 2, locomotor effects of sub
      chronic administration of dexamphetamine (1.0 mg/kg/i.p.) were analyzed in HR and
      LR for 5 consecutive days. HR showed a higher locomotor response to
      dexamphetamine than LR; however, the two groups did not differ in their
      sensitization rate. It is concluded that there are neither major HR-LR
      differences in the locomotor response to acute administration of various doses of
      dexamphetamine nor HR-LR differences in the rate of sensitization of this
      locomotor response to sub-chronic administration of dexamphetamine. Type-specific
      differences in the mutual interaction between corticosteroids and dexamphetamine
      as well as the nature of the chosen dependent variable, namely locomotor
      activity, are hypothesized to underlie the results of the present study.

PMID- 9259015
TI  - Neuropharmacological effects of low and high doses of repeated oral
      dexfenfluramine in rats: a comparison with fluoxetine.
AB  - The neuropharmacological effects of repeated oral doses of dexfenfluramine (DF;
      1.25-10 mg/kg, twice daily for 21 days) were examined in rats and related to the
      drug brain levels. Results were compared with fluoxetine (FL) given at similar
      doses relative to its anorectic ED50. Both drugs dose-dependently slowed body
      weight gain and reduced brain serotonin (5-HT). However, at 1.25 mg/kg DF caused
      only a slight and transient decrease in cortical 5-HT. Comparable doses of FL
      (6.25-12.5 mg/kg) lowered 5-HT more than DF, besides slightly reducing striatal
      dopamine. At higher doses DF markedly reduced 5-HT in all regions, and to a
      lesser extent noradrenaline in hippocampus. There was a negative relationship
      between 5-HT and log total active drug levels and the indole was approximately
      halved at drug levels about 50 times lower with DF than FL. However, the ratio
      between drug levels causing marked 5-HT reductions and those considered anorectic
      was similar for DF and FL because brain levels at the anorectic ED50 were higher
      with FL than DF. Long-lasting reductions of 5-HT were also observed but recovery
      was only consistently slow beginning from 5 mg/ kg DF. Comparable doses of FL
      could not be used because its general toxicity leads to the death of rats after
      only 2-4 multiples of its anorectic ED50.

PMID- 9259017
TI  - Effect of apomorphine on the conflict-induced jumping stereotypy in bank voles.
AB  - In conventional laboratory cages, bank voles (Clethrionomys glareolus) develop a
      jumping up-and-down stereotypy already before the age of one month. Central DA
      systems are thought to be involved in the expression of these conflict-induced
      stereotypies (CIS). Stereotypies can also be elicited pharmacologically, most
      commonly by amphetamine and apomorphine. Hence, administration of apomorphine to
      jumping bank voles provides the opportunity to compare pharmacologically-induced
      stereotypies (PHIS) and CIS in that species. A pilot study showed that
      apomorphine induced stereotyped licking that is qualitatively different from the
      CIS elicited by captivity. The present study investigated whether apomorphine has
      an effect on CIS-levels. The lowest dose (0.625 mg/kg) did not elicit licking but
      neither influenced jumping levels. Higher doses (0.938 and 1.094 mg/kg) lead to
      the occurrence of licking but also suppressed CIS-levels. However, the
      discordance in time profiles of licking and jumping argues against a shift from
      jumping to licking due to further stimulation of already activated DA systems.
      Therefore, expression of jumping seems to depend on stimulation of other DA
      receptor subtypes or jumping may even be DA independent.

PMID- 9259018
TI  - Normalizing effects of nicotine and a novel nicotinic agonist on hippocampal
      auditory gating in two animal models.
AB  - Rapid habituation of the evoked response to repeated auditory stimuli is a
      physiological manifestation of sensory gating mechanisms that are disturbed in
      human psychoses. Similar deficits are found in two animal models: fimbria-fornix
      lesioned Sprague-Dawley rats and DBA/2 mice, an inbred strain with decreased
      numbers of hippocampal alpha 7 nicotinic receptors. In response to paired
      auditory stimuli, the hippocampal evoked response of outbred, unlesioned animals
      is larger to the first than to the second stimulus. Both fimbria-fornix lesioned
      rats and DBA/2 mice have decreased response to the first stimulus but no further
      suppression of response to the second stimulus. Parenteral administration of (S)
      3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT418), a newly developed
      nicotinic agonist, was found to normalize hippocampal auditory evoked responses
      in both models. The response to the first stimulus was increased, and the
      response to the second stimulus was suppressed relative to the first. The
      magnitude and time course of effect were similar to those observed with a 10-fold
      greater dose of nicotine. Both nicotine and ABT418 were ineffective when a second
      dose was administered 1 h later, suggesting that both compounds may desensitize
      the receptor mechanism.

PMID- 9259019
TI  - Regional densities of benzodiazepine sites in the CNS of alcohol-naive P and NP
      rats.
AB  - The regional densities of benzodiazepine (BDZ) recognition sites coupled to GABAA
      receptors were studied in ethanol-naive alcohol-preferring (P) and -nonpreferring
      (NP) lines of rats by using quantitative autoradiography to measure the amount of
      2 nM [3H]flunitrazepam (FNZ) binding in the absence and presence of 100 microM
      GABA. Lower values (p < 0.025) for [3H]FNZ binding (in the absence of GABA) were
      observed in the prefrontal cortex, layer 4 of the parietal cortex, and the
      nucleus accumbens shell of the P relative to the NP line. GABA significantly (p <
      0.025) stimulated [3H]FNZ binding in all 50 central nervous system regions
      examined in both the P and the NP rats. The largest percent increases (190-220%)
      were observed in the prefrontal, cingulate, frontal, and parietal cortices; shell
      and core nucleus accumbens; caudate putamen; dorsal lateral, intermediate
      lateral, ventral lateral, and medial septal nuclei; and lateral hypothalamus. In
      several layers of the frontal and parietal cortices, a 25-30% greater net or
      percent increase (p < 0.025) in GABA-enhanced [3H]FNZ binding was observed in the
      P rats compared with the NP rats. In contrast, lower net or percent increases (p
      < 0.025) in GABA-enhanced [3H]FNZ binding were found in the entorhinal cortex,
      the mediodorsal thalamus, and the dorsal CA3 area and middle dentate gyrus of the
      posterior hippocampus of the P line relative to the NP line. The present findings
      suggest that there are innate regional differences between P and NP rats in the
      densities and/or affinities of BDZ recognition sites and in the coupling between
      the GABAA and BDZ binding sites.

PMID- 9259020
TI  - Evidence for a depressive-like state induced by repeated saline injections in
      Fischer 344 rats.
AB  - We investigated the behavioral changes induced by mild stress in animals that may
      be relatively susceptible to a depressive-like state, the Fischer 344 rat strain.
      The mild stress of repeated handling and intraperitoneal (i.p.) injections with
      saline (2 ml/kg, twice a day for 14 days) elicited a moderate suppression of body
      weight gain, a decrease in open field activity, and a prolonged immobility during
      the tail suspension test in Fischer 344 rats compared with Sprague-Dawley rats.
      Chronic treatment of Fischer 344 rats with imipramine (10 mg/kg i.p., twice a day
      for 14 days) effectively suppressed open field activity and prolonged immobility.
      These results suggest that repeated saline injections may be a mild stressor in
      these rats. In the Fischer 344 strain, which may be vulnerable to the effects of
      mild stressors, repeated saline injections might induce a depressive-like state
      and could presumably represent an experimental model for depression.

PMID- 9259021
TI  - Effects of perospirone (SM-9018), a potential atypical neuroleptic, on dopamine
      D1 receptor-mediated vacuous chewing movement in rats: a role of 5-HT2 receptor
      blocking activity.
AB  - We compared the acute and subacute effects of perospirone (SM-9018), a novel
      neuroleptic with potent 5-HT2 and D2 blocking actions, and of haloperidol (HAL)
      on dopamine D1 receptor-mediated vacuous chewing movement (VCM) in rats. A
      selective D1 agonist, SKF 38393 (SKF), markedly increased the incidence of VCM,
      which was blocked by SCH 23390 (a D1 antagonist) but not by sulpiride (a D2
      antagonist). Perospirone and HAL inhibited the SKF-induced VCM in a dose
      dependent manner. The potency of the inhibitory actions of perospirone was
      considerably weaker (about 30 times) than that of HAL despite their similar
      affinities for D1 receptors. Subacute treatment with perospirone for 2 weeks
      failed to affect the behavioral sensitivity of rats to SKF. However, the HAL
      treatment markedly enhanced the incidence of the SKF-induced VCM. On the other
      hand, the selective 5-HT2 antagonists ritanserin and ketanserin significantly
      reduced the inhibitory actions of HAL and SCH 23390 on the SKF-induced VCM. In
      addition, combined treatment of ritanserin with HAL for 2 weeks abolished the
      enhancement of SKF-induced VCM by HAL treatment. These findings suggest that
      perospirone is weaker than HAL in altering the behavioral sensitivity of D1
      receptor-mediated VCM under repeated administration, which may be related to the
      5-HT2 blocking activity of perospirone.

PMID- 9259022
TI  - An ethopharmacological analysis of selective activation of 5-HT1A receptors: the
      mouse 5-HT1A syndrome.
AB  - The behavioral effects of 8-OH-DPAT [0.5-10 mg/kg intraperitoneally (i.p.)] and
      (+) S-20499 (1-20 mg/kg IP), a recently synthesized 5-HT1A receptor full agonist,
      were examined over a 2-h period in mice in a neutral cage and, during the peak
      period of effect, in a runway, 8-OH-DPAT (1 and 10 mg/kg) and (+) S-20499 (10 and
      20 mg/kg) blocked vertical activity (i.e., rearing and hanging on the wire mesh)
      during the period postinjection when levels of activity of the control mice were
      high. In this initial period (0-30 min), mice treated with 8-OH-DPAT, but not
      those treated with (+) S-20499, displayed flat back rather than curve back
      locomotion (0.5-10 mg/kg). However, after about 50 min., marked hyperactivity
      emerged for 8-OH-DPAT at 0.5 and 1 mg/kg and for (+) S-20499 at all doses,
      including increases in rearing, hanging, grooming, and for (+) S-20499, curve
      back locomotion. Both 8-OH-DPAT (10 mg/kg) and (+) S-20499 (> 20 mg/kg)
      significantly enhanced eating responses. Both drugs rapidly induced straub tail
      responses at all doses, and this effect remained significant until the end of the
      experiment at the highest doses. Subjects treated with 0.5 mg/kg of 8-OH-DPAT and
      10 mg/kg of (+) S-20499 displayed in the initial time period "ballistic-type"
      rapid forelimb movements targeted toward the side of the head. During peak drug
      effect periods, higher doses of both drugs produced significant increases in
      movement with a change of direction, including rotation around the hindlimbs,
      suggesting, as do the ballistic-type movements, particular involvement of the
      forelimbs. These findings provide evidence consonant with the view that selective
      activation of 5-HT1A receptors in mice produces distinct behavioral changes in
      part associated with the 5-HT syndrome. Moreover, these changes differ, in the
      specific movements induced and in the drug parameters and time course of changes,
      from those reported in the laboratory rat.

PMID- 9259023
TI  - Competitive NMDA and strychnine-insensitive glycine-site antagonists disrupt
      prepulse inhibition.
AB  - Prepulse inhibition (PPI) is thought to reflect the operation of a sensorimotor
      gating system in the brain. Sensorimotor gating abnormalities have been
      identified in schizophrenic patients, and various neural systems are involved in
      this function. To study the modulation of the sensorimotor gating system by the N
      methyl-D-aspartate (NMDA) receptor channel complex, the effects of noncompetitive
      and competitive NMDA antagonists on PPI were examined in rats. PPI was not
      disrupted by CGS 19755, a competitive NMDA antagonist, at 30 min after
      subcutaneous (s.c.) administration. However, CGS 19755 (40 mg/kg s.c.) decreased
      PPI at 120 min after administration with a marked decrease of startle amplitude.
      Late onset of the effect of CGS 19755 was also observed in the increase of
      spontaneous locomotor activity (SLA). On the other hand, phencyclidine, a
      noncompetitive NMDA antagonist, disrupted PPI at 30 min after administration and
      increased SLA from 20 min after administration. PPI was also disrupted by
      bilateral intracerebroventricular administration of 5,7-dichlorokyn urenate (10
      and 20 micrograms/side X 2), an antagonist at the strychnine-insensitive glycine
      receptor, which is an allosteric binding site in the NMDA receptor-channel
      complex. It is concluded that the NMDA receptor-channel complex plays an
      important role in regulation of PPI.

PMID- 9259024
TI  - Both nicotinic and muscarinic receptors in ventral tegmental area contribute to
      brain-stimulation reward.
AB  - Cholinergic neurons of the pedunculopontine tegmental nucleus (Ch5) and
      laterodorsal tegmental nucleus (Ch6) monosynaptically activate dopamine neurons
      of the substantia nigra and ventral tegmental area (VTA) via nicotinic and
      muscarinic receptors. The nicotinic receptors near the VTA have been proposed to
      be important for nicotine self-administration in rats and for tobacco smoking in
      humans. Nicotinic and muscarinic blockers were microinjected into the VTA of rats
      trained to lever-press for lateral hypothalamic stimulation via an ipsilateral
      electrode. The competitive nicotinic blocker dihydro-beta-erythroidine (DH beta
      E; 5-60 micrograms) shifted rate-frequency curves to the right by a mean of 6-27%
      in a dose-related manner; the noncompetitive nicotinic blocker mecamylamine (10
      300 micrograms) produced similar shifts of 7-21%. Atropine (30 micrograms)
      shifted the curves to the right by a mean of 82% in three of the sites tested
      with DH beta E. All blockers decreased maximum bar-pressing rates significantly
      in some sites when the shifts were large. Therefore, nicotinic receptors in the
      VTA make small contributions to the maintained rewarding effect of brain
      stimulation reward in rats, but muscarinic receptors in the VTA appear to be more
      important.

PMID- 9259025
TI  - Physiological and subjective effects of acute cocaine withdrawal (crash) in rats.
AB  - The physiological and subjective effects of high acute doses of cocaine and the
      subsequent homeostatic acute withdrawal syndrome were measured in rats.
      Radiotelemetry recordings of body temperature and activity were monitored in rats
      for 48 h after 32 mg/kg cocaine (COC) and saline (SAL) were administered by both
      intraperitoneal and subcutaneous (s.c.) routes. COC initially produced
      hypothermia and hyperactivity, followed by a prolonged hyperthermic and
      hypoactive rebound that seemed to peak around 12 h after injections. The s.c.
      route of administration produced the greatest rebound effect. Eight additional
      rats were monitored for EEG activity by telemetry for 48 h after SC
      administration of SAL or 32 mg/kg COC. COC produced an initial decrease in alpha
      and beta wavelength bands, with a trend toward increases in alpha and beta power
      demonstrated from the 10th through 14th h after injections. Using a three-choice
      haloperidol (HDL), saline, and COC drug discrimination task, we demonstrated a
      COC-like subjective state produced during the 10th through 12th h after a 32
      mg/kg s.c. COC injection with no HDL-like responding engendered during any tested
      period of the acute or rebound effects of COC. These data provide evidence for an
      acute COC withdrawal syndrome (crash) in rats occurring 10-14 h after a high-dose
      COC treatment.

PMID- 9259026
TI  - Current controversies in the application of meta-analysis (with special reference
      to oncological treatments). A commentary.

PMID- 9259027
TI  - Apoptosis: molecular mechanisms and implications for cancer chemotherapy.
AB  - Apoptosis, or programmed cell death, is an orderly and genetically controlled
      form of cell death. In a morphological sense, it differs from necrosis in that
      cellular shrinkage and chromatin condensation occurs, followed by fragmentation
      of nuclear components within membrane-bound vesicles which are cleared by
      phagocytosis without damage to adjacent tissue. The molecular pathway includes an
      initiating phase, which starts after signalling by external triggers, such as
      ligation to distinct receptors or by endogenous mechanisms related to aging or to
      exogenous irreversible cellular or nuclear damage. The initiation phase is
      followed by a decision phase. During this phase transduction occurs of the
      apoptotic signal to nuclear and cytoplasmatic target enzymes, which includes
      activation of endonucleases and enzymatic alterations of the cytoskeleton. There
      are numerous proteins and lipid-derived moieties which modulate the apoptotic
      mechanism in positive or negative direction. The execution phase is started when
      the cell has arrived at a stage of no return. The nuclear DNA is cleaved into
      multiples of 180-200 basepairs, the plasma membrane integrity and the
      mitochondria remain initially intact, the cell splits up into apoptotic bodies,
      small vesicles which enclose the nuclear and cellular remnants. Finally, the
      clearing phase is arrived, when the apoptotic bodies are phagocytosed by adjacent
      cells and macrophages. It is thought that the pharmacodynamics of anticancer
      drugs consists of two distinct steps. The first step includes the interaction
      with its cellular target; which is not lethal per se. The commitment of the cell
      to undergo apoptosis forms the second step. The efficacy of anticancer drugs is
      determined by the ability to selectively sensitize tumor cells to apoptosis,
      which depends to a large extent from the expression of various oncogenes, such as
      bcl-2, p53, bax, ras, c-myc and others, and from endogenous factors. It is a
      challenge in pharmacological research to explore apoptosis by modulating the
      extrinsic and intrinsic regulators in a positive or negative direction in order
      to improve the efficacy of anticancer treatment.

PMID- 9259028
TI  - Hyperhomocysteinaemia and associated disease.
AB  - An elevated plasma homocysteine level may result from various environmental and
      genetic factors. Herediatary causes of severe hyperhomo-cysteinaemia are very
      rare and usually lead to disease in childhood or adolescence. Common pathology
      consists of early atherosclerotic vascular changes, arterioocclusive
      complications and venous thrombosis. Mildly elevated genetically determined
      plasma homocysteine levels are observed in 5% of the general population. In the
      last two decades research has shown mild hyperhomocysteinaemia to be linked to an
      increased risk of premature atherosclerosis, pregnancies complicated by neural
      tube defects and early pregnancy loss, and venous thrombosis. Homozygosity for
      thermolabile MTHFR deficiency has been identified as one important genetic
      factor, which expression is modified by dietary folate intake. Although mild
      hyperhomocysteinaemia can easily be treated by vitamin supplementation the
      beneficial effects of such treatment remains to be shown.

PMID- 9259029
TI  - The treatment of staphylococcal infections with special reference to
      pharmacokinetic, pharmacodynamic and pharmacoeconomic considerations.
AB  - The choice of antibiotics for the treatment of staphylococcal infections depends
      to a high degree on the susceptibility patterns in the hospital in question.
      These may be highly variable and considerable differences between countries and
      hospitals exist. The insight into the pharmacodynamic aspects of antimicrobial
      agents has increased considerably in the last 5 years, resulting in new
      treatments, such as once daily administration of aminoglycosides and continuous
      infusion of betalactam antibiotics. The antibiotic policy in Dutch hospitals for
      the treatment of staphylococcal infections is discussed. In most Western
      countries with a relatively low incidence of MRSA, penicillin-derivatives, such
      as flucloxacillin (or cloxacillin, methicillin and nafcillin) will be the drug of
      choice, because of their good in-vitro activity, low toxicity, good clinical
      efficacy and relatively low cost. If the incidence of MRSA increases, drugs such
      as the glycopeptides will be of more importance. This will of course have a clear
      economic impact, as both vancomycin and teicoplanin are considerably more
      expensive than agents such as flucloxacillin and oral treatment is not possible.
      Pharmacoeconomic aspects also play a role. As a rule, intravenous antimicrobial
      agents are considerably more expensive than the oral formulations. Before oral
      administration can be recommended, a reliable oral absorption, also in seriously
      ill patients, must have been demonstrated. Other aspects that influence the cost
      of therapy are hospital stay and the possibility of outpatient treatment.

PMID- 9259030
TI  - Pharmacokinetic modelling of intravenous tobramycin in adolescent and adult
      patients with cystic fibrosis using the nonparametric expectation maximization
      (NPEM) algorithm.
AB  - The availability of personal computer programs for individualizing drug dosage
      regimens has stimulated the interest in modelling population pharmacokinetics.
      Data from 82 adolescent and adult patients with cystic fibrosis (CF) who were
      treated with intravenous tobramycin because of an exacerbation of their pulmonary
      infection were analysed with a non-parametric expectation maximization (NPEM)
      algorithm. This algorithm estimates the entire discrete joint probability density
      of the pharmacokinetic parameters. It also provides traditional parametric
      statistics such as the means, standard deviation, median, covariances and
      correlations among the various parameters. It also provides graphic-2- and 3
      dimensional representations of the marginal densities of the parameters
      investigated. Several models for intravenous tobramycin in adolescent and adult
      patients with CF were compared. Covariates were total body weight (for the volume
      of distribution) and creatinine clearance (for the total body clearance and
      elimination rate). Because of lack of data on patients with poor renal function,
      restricted models with non-renal clearance and the non-renal elimination rate
      constant fixed at literature values of 0.15 L/h and 0.01 h-1 were also included.
      In this population, intravenous tobramycin could be best described by median (+/
      dispersion factor) volume of distribution per unit of total body weight of 0.28
      +/- 0.05 L/kg, elimination rate constant of 0.25 +/- 0.10 h-1 and elimination
      rate constant per unit of creatinine clearance of 0.0008 +/- 0.0009 h
      1/(ml/min/1.73 m2). Analysis of populations of increasing size showed that using
      a restricted model with a non-renal elimination rate constant fixed at 0.01 h-1,
      a model based on a population of only 10 to 20 patients, contained parameter
      values similar to those of the entire population and, using the full model, a
      larger population (at least 40 patients) was needed.

PMID- 9259031
TI  - Current controversies in the application of meta-analysis (with special reference
      to oncological treatments)
AB  - Meta-analysis was proposed more than 20 years ago as an innovative technique for
      pooling the results of a series of clinical studies. This technique has a two
      fold purpose: i) to retrieve pertinent clinical information without introducing
      selection biases; ii) to combine these clinical data obtained from different
      sources into a single synthetic index that summarises all available information.
      This review highlights the current perspectives in the application of meta
      analysis and places particular emphasis on discussing the limitations of this
      technique that have been identified in recent years. Specific controversies in
      this area include: i) comparison between meta-analysis of the literature and meta
      analysis of individual patient data; ii) heterogeneity of the clinical material
      introduced in the meta-analytic pooling; and iii) survival meta-analysis as a
      method for pooling long-term outcome data. After debating these three
      controversial points, this review examines the newest uses of meta-analysis that
      have been proposed for the evaluation of cost-effectiveness data and tries to
      identify the meta-analytic applications that will probably be expanded in the
      near future as opposed to those that will instead be developed less and less.

PMID- 9259032
TI  - Drive theory revisited.
AB  - Fallacious energic formulations and phylogenetic oversimplifications have led
      drive theory into disfavor. However, the advantages of a drive concept based on
      evolutionary principles outweigh the disadvantages. A psychological drive concept
      best captures the innately endowed, self-enhancing motivational push compatible
      with evolutionary principles, while at the same time being consonant with the
      intrapsychic dynamics of psychoanalytic observation. Current evolutionary
      principles and their implications are discussed. Incorporating these principles
      as cogent theoretical postulates is a crucial part of maintaining a link to the
      natural sciences and thereby to our involvement in the great enterprise of
      elaborating a comprehensive psychology. To exclude these concepts is to promote a
      detachment from our involvement in the natural sciences and to lose a powerful
      heuristic guide for our theoretical endeavors.

PMID- 9259033
TI  - Integrating one-person and two-person psychologies: autochthony and alterity in
      counterpoint.
AB  - The classical psychoanalytic concept of the one-person treatment model and its
      assumptions concerning psychic reality are compared with the contemporary two
      person model, subsumed under the concept of "alterity" (otherness). The classical
      model of unconscious mental life is explored in terms of the principles of
      "autochthony" (signifying the fantasy that self and object are created entirely
      from and by the self) and "cosmogony" (an aspect of primary and secondary
      processes that accounts for the creation of a personal and an objective world
      view). Autochthony and cosmogony are subsumed under the category of
      "creationism." I discuss why I identify these three phenomena by these relatively
      unused terms.

PMID- 9259034
TI  - Deconstructing the myth of the neutral analyst: an alternative from
      intersubjective systems theory.
AB  - A critique is offered of four conceptions of neutrality that have been prominent
      in the psychoanalytic literature: neutrality as (1) abstinence, (2) anonymity,
      (3) equidistance, and (4) empathy. It is argued that once the psychoanalytic
      situation is recognized as an intersubjective system of reciprocal mutual
      influence, the concept of neutrality is revealed to be an illusion. Hence,
      interpretations are always suggestions, transference is always contaminated, and
      analysis are never objective. An alternative to neutrality is found in the
      investigatory stance of empathic-introspective inquiry. This mode of inquiry is
      sharply distinguished from the prescribing of self-expressive behavior on the
      part of analysis, and the distinction is illustrated with a clinical vignette.

PMID- 9259035
TI  - When the analyst is ill: dimensions of self-disclosure.
AB  - This article examines questions related to the "inescapable," the "inadvertent,"
      and the "deliberate" personal disclosures by an analyst. Technical and personal
      considerations that influence the analyst's decision to disclose, as well as the
      inherent responsibilities and potential clinical consequences involved in self
      disclosure, are explored, with particular attention to transference
      countertransference dynamics, therapeutic goals, and the negotiation of
      resistance. The author describes her clinical work during a period of prolonged
      illness, with case vignettes that illustrate how-self-disclosure may be regarded
      as both an occasional authentic requirement and a regular intrinsic component of
      clinical technique.

PMID- 9259036
TI  - The interactive paradigm and a psychoanalytic paradox.
AB  - This paper examines the new "interactive" theorizing in the context of a
      fundamental paradox of psychoanalytic practice which has shaped theories of
      technique beginning with Freud. The paradox resides in the extent to which the
      work of psychoanalysis depends upon undependable capacities of the patient. This
      tension creates pressures on psychoanalytic practitioners which are often
      reflected in the creation of new theory in an effort to find "ways out" of the
      paradox. I propose that many of the significant historical shifts in our theories
      of technique, including the current "paradigm shift" emphasizing interactive
      aspects of psychoanalysis, have been surprisingly kindred efforts at "solving"
      the problems of this paradox.

PMID- 9259037
TI  - Primary femininity, bisexuality, and the female ego ideal: a re-examination of
      female developmental theory.
AB  - While the concept of primary femininity advances our understanding of the girl's
      developmental experience, a number of contradictions and problematic assumptions
      are at the present time contained within this concept. I propose that we use the
      phrase "primary sense of femaleness" to refer to the girl's earliest sense of
      self deriving from the mental representation of her body. In addition, I argue
      that the concepts of a primary sense of femaleness and of a bisexual matrix are
      not mutually exclusive; an early sense of self located in a female body can co
      exist with the fantasy of potential unlimited by gender. Finally, I examine the
      role of the mother as ego ideal for the girl.

PMID- 9259038
TI  - National trends of research in psychology and psychiatry (1981-1995)

PMID- 9259039
TI  - Agoraphobia and panic disorder: 3.5 years after alprazolam and/or exposure
      treatment.
AB  - BACKGROUND: Long-term follow-ups after controlled studies of exposure therapy for
      agoraphobia/panic are few. Most of these studies found that improvement during
      treatment persists to the end of follow-up. METHODS: Out of 69 patients with
      panic disorder plus agoraphobia who had been in an 8-week controlled study of
      alprazolam and/or exposure, 31 were followed up at a mean of 3.5 years later (4
      years after trial entry). The 31 patients followed up included more cases who had
      relapsed at week 43 than did the group which did not attend the 3.5-year follow
      up. RESULTS: As a group, followed-up cases maintained their gains over the 3.5
      years, more so among ex-exposure than ex-relaxation cases. Ex-exposure patients
      did significantly better than relaxation patients on disability and survival
      time. Ex-alprazolam and ex-exposure patients did not differ significantly on any
      variable at the 3.5-year follow-up. No baseline variable predicted outcome at
      follow-up. CONCLUSIONS: Present results modestly confirm those of previous
      studies finding lasting improvement years after exposure, though some residual
      symptoms were the norm.

PMID- 9259040
TI  - Evidence for a sex-specific residual effect of cannabis on visuospatial memory.
AB  - BACKGROUND: In an exploratory study, we used a novel computerized battery of
      neuropsychological tests of attention to assess residual cognitive impairment in
      marijuana users. METHODS: We compared 25 college students who were heavy
      marijuana smokers (who had smoked a median of 29 days in the last 30 days) with
      30 students who were light smokers (who had smoked a median of 1 day in the last
      30 days). All subjects were tested after a supervised period of abstinence from
      marijuana and other drugs lasting at least 19 h. RESULTS: Differences between the
      overall groups of heavy and light smokers did not reach statistical significance
      on the four subtests of attention administered. However, upon examining data for
      the two sexes separately, marked and significant differences were found between
      heavy- and light-smoking women on the subtest examining visuospatial memory. On
      this test, subjects were required to examine a 6 x 6 'checkerboard' of squares in
      which certain squares were shaded. The shaded squares were then erased and the
      subject was required to indicate with the mouse which squares had formerly been
      shaded. Increasing numbers of shaded squares were presented at each trial. The
      heavy-smoking women remembered significantly fewer squares on this test, and they
      made significantly more errors than the light-smoking women. These differences
      persisted despite different methods of analysis and consideration for possible
      confounding variables. CONCLUSIONS: This observation suggests that it may be
      important to study the residual effects of marijuana on men and women separately
      particularly since women have been greatly underrepresented in previous studies
      in this area.

PMID- 9259041
TI  - Immune effects of relaxation during chemotherapy for ovarian cancer.
AB  - BACKGROUND: Psychological interventions, such as relaxation training, have been
      applied to strengthen resistance to disease. There is evidence that relaxation
      can modify immune parameters in healthy populations and in chemotherapy naive
      cancer patients. METHODS: In this study, 22 patients receiving chemotherapy for
      ovarian cancer were allocated to relaxation training with a clinical psychologist
      or to a control group. After 2 months' training, blood was sampled 2 days before
      chemotherapy in the patients' homes, and at the hospital prior to treatment.
      RESULTS: On average, the intervention group showed higher lymphocyte counts, and
      a tendency to higher white blood cell numbers as compared to the control group.
      No significant effects were found in proliferative responses to mitogen and
      natural killer cell activity after intervention. Relaxation training did not
      modify the magnitude of changes in immune variables between home samples and at
      the hospital in anticipation of treatment. CONCLUSIONS: The study suggests that
      relaxation training can positively affect immune parameters in cancer patients,
      even if training is performed during myelosuppressive therapy.

PMID- 9259042
TI  - Effects of job strain on helper-inducer (CD4+CD29+) and suppressor-inducer
      (CD4+CD45RA+) T cells in Japanese blue-collar workers.
AB  - BACKGROUND: The effects of job strain on helper-inducer (CD4+CD29+) T cells and
      suppressor-inducer (CD4+CD45RA+) T cells are not clear. METHODS: The subjects
      were 65 male blue-collar workers in a chemical plant in Japan. Perceived job
      stressors were assessed using the Japanese version of Job Content Questionnaire,
      i.e., job demands, job control, supervisor support and coworker support. Blood
      samples were taken from these subjects, and number and percentage of total
      lymphocytes were calculated for total T cells, helper (CD4+) T cells,
      suppressor/cytotoxic (CD8+) T cells, helper-inducer (CD4+CD29+) T cells and
      suppressor-inducer (CD4+CD45RA+) T cells using the double-staining fluorescence.
      RESULTS: Job control significantly and positively correlated with number and
      percentage of helper-inducer (CD4+CD29+) T cells, after controlling for age,
      number of cigarettes per day and blood lead concentration (Spearman's partial
      correlation, p < 0.05), while job demands, supervisor support or coworker support
      did not (p > 0.05). The job strain index, i.e., the ratio of job demands to job
      control, significantly and negatively correlated with the percentage of helper
      inducer (CD4+CD29+) T cells (p < 0.05). None of the job stress scales
      significantly correlated with number or percentage of suppressor-inducer
      (CD4+CD45RA+) T cells (p > 0.05). CONCLUSIONS: It is suggested that higher job
      strain or lower job control is associated with a decrease in helper-inducer
      (CD4+CD29+) T cells in Japanese blue-collar workers.

PMID- 9259043
TI  - Chronic caregiving stress alters peripheral blood immune parameters: the role of
      age and severity of stress.
AB  - BACKGROUND: To examine the impact of chronic psychological stress on the immune
      system, a series of cellular and humoral immunological parameters was compared in
      18 female caregivers of handicapped people and 18 age- and sexmatched controls.
      METHODS: The immunological parameters included assessment of T cell number (T
      cells, T helper, and T suppressor/cytotoxic) and function (delayed-type cutaneous
      hypersensitivity), antibody titers for latent herpesviruses (cytomegalovirus and
      herpes simplex virus 1 and 2), and markers of inflammation (complement C3 and C4
      factors and c-reactive protein). Serum immunoglobulins (IgG, IgM, IgA, IgE) and
      titers for the nonlatent virus roseola were used to control for nonspecific
      elevations in serum proteins. Results were associated with the age of the
      investigated subjects, the severity of stress (family burden) and the degree of
      disability of the handicapped people. RESULTS: Caregivers had a significantly
      lower percentage of T cells, a significantly higher percentage of T
      suppressor/cytotoxic cells and a significantly lower T helper:suppressor ratio.
      Subjects were also analyzed after division into two groups according to the
      median age (45 years). Compared to their matched controls, older caregivers (mean
      age = 50.3) also had lower numbers of T cells and T helper cells and higher
      antibody titers for cytomegalovirus. In addition, in the caregiver population
      severity of stress was significantly positively correlated with T
      suppressor/cytotoxic cells and negatively correlated with T helper:suppressor
      ratio. No other differneces in the immune parameters were found between
      caregivers and controls. CONCLUSIONS: The results indicate that psychological
      stress differentially affects various aspects of the immune system and confirm
      the relevant role of age and severity of stress in modulating these influences.

PMID- 9259044
TI  - Alexithymia, immunity and cervical intraepithelial neoplasia: replication.
AB  - BACKGROUND: In a previous study [Psychother Psychosom 1994;61:199-204] we
      investigated the relationship between alexithymia, carcinogenesis and immunity in
      a group of women who were unconscious sufferers from precancerous lesions of the
      cervix (CIN). The results of this study showed a high level of association
      between alexithymia and CIN and, an even more interesting fact, between
      alexithymia and reduced levels of immunity. METHODS: The aim of the present study
      is to check the results of the previous one by testing a larger group (43 women
      affected by cervical dysplasia and 67 healthy women) and by the use of a self
      administered test for detection of alexithymia, the well-validated Twenty-Item
      Toronto Alexithymia Scale (TAS-20). RESULTS: The results confirm that women
      suffering from CIN have higher average TAS-20 ratings (55) than normal women
      (47.32) and that the level of alexithymia detected in the group of women
      suffering from dysplasia (42.5%) is higher than that of normal women (12.85%).
      Moreover, the present study confirms that alexithymic women have lower rates of a
      number of lymphocyte subsets than non-alexithymic women. CONCLUSIONS: This study
      fully confirms the results of our previous work and those of a number of other
      studies: (1) personality might be one of the factors jointly responsible for the
      outbreak of cancer; (2) the immune system appears to play an important part as a
      mediator between personality and cancer.

PMID- 9259045
TI  - Eating disorders in Austrian men: an intracultural and crosscultural comparison
      study.
AB  - BACKGROUND: We compared 30 male university students with eating disorders and 30
      male comparison subjects without eating disorders recruited by advertisement at
      Innsbruck University, Austria. METHODS: Subjects were interviewed using
      instruments that we had previously used in a controlled study of college men with
      eating disorders in the United States. RESULTS: The Austrian men with eating
      disorders differed sharply from Austrian comparison subjects, but closely
      resembled their American counterparts, on prevalence of personal and familial
      psychopathology, adverse family experiences, and scores on rating scales for
      eating disorder. Interestingly, dissatisfaction with body image was consistently
      greater among American subjects regardless of eating disorder status.
      CONCLUSIONS: Our data suggest a weak association between eating disorders and
      homosexual or bisexual orientation in men and no consistent association between
      eating disorders and childhood sexual abuse.

PMID- 9259046
TI  - Two hearts beat as one [corrected].

PMID- 9259047
TI  - Mitogenic activation of the transferrin receptor gene promoter is modulated by
      inhibitors of tyrosine kinases and tyrosine phosphatases.
AB  - Transferrin receptor gene expression is coupled to cell proliferation of normal
      cells and is elevated in nearly all types of tumor cells. A mitogen-responsive
      region of the transferrin receptor gene promoter has been localized between -78
      and -34 relative to the major transcriptional start. The promoter can be
      activated in quiescent fibroblasts by treatment with either vanadate or
      phenylarsine oxide, both of which are inhibitors of tyrosine phosphatases and
      lead to elevated levels of intracellular tyrosine-phosphorylated proteins.
      Vanadate can act synergistically with other mitogens and, when added together
      with serum, leads to superactivation of the promoter. Genistein, an inhibitor of
      certain tyrosine kinases, actually enhances promoter activity in cells treated
      with either vanadate or phenylarsine oxide. On the other hand, geldanamycin,
      which also reduces the level of tyrosine-phosphorylated proteins and promoters
      the morphological reversion of many transformed cell types, is a potent inhibitor
      of transferrin receptor promoter activation by mitogens. The differential effects
      of these two tyrosine kinase inhibitors is most likely caused by the specificity
      of the enzymes that they target. These results indicate that a tyrosine
      phosphorylation event plays a critical role in the signaling events that lead to
      activation of the transferrin receptor gene promoter in mitogen-stimulated cells.
      This is of interest because activation of this promoter is a delayed response
      that occurs several hours after mitogen addition.

PMID- 9259048
TI  - Effects of hypertonic sucrose and potassium depletion on the binding properties
      of beta and alpha 1 adrenergic receptors measured on intact cells.
AB  - The effects of hypertonic sucrose and of intracellular potassium depletion on the
      intact-cell-binding properties of beta (beta AR) and alpha 1 (alpha 1AR)
      adrenergic receptors of DDT1 MF-2 hamster smooth muscle cells were investigated.
      These treatments are known to block clathrin assembly into coated pits, an early
      step in the pathway of receptor endocytosis. Conducting intact-cell-binding
      assays in the presence of 0.4 M sucrose markedly decreased the fraction of both
      beta ARs and alpha 1ARs converted during the assay to a form exhibiting low
      apparent affinity for agonists. Intracellular potassium depletion also decreased
      the fraction of both beta ARs and alpha 1ARs converted to this low-affinity form.
      In contrast the intact-cell-binding properties of antagonists were unaltered by
      these treatments. These results suggest a role for receptor internalization in
      conversion of both beta ARs and alpha 1ARs to their low-affinity forms. A model
      is proposed in which either an initial agonist-induced receptor sequestration
      within the plasma membrane or the subsequent endocytosis of receptors into
      intracellular vesicles allows conversion of these receptors to the form
      exhibiting low affinity for agonists in binding assays with intact cells.

PMID- 9259049
TI  - Identification of a glucocorticoid repressor domain in the rat beta 1-adrenergic
      receptor gene.
AB  - The expression of the gene encoding the rat beta 1-adrenergic receptor is
      suppressed by glucocorticoids (Kiely et al., 1994). Within the 3.2-kb 5'-flanking
      region of the promoter, two potential glucocorticoid response elements (GREs) at 
      950 and -2791 relative to the translational ATG were identified. Characterization
      of the glucocorticoid-responsive sequences in the 5'-flanking region of the beta
      1-adrenergic receptor gene was explored in rat C6 glioma cells and human HepG2
      hepatoma cells using transient expression of beta 1-adrenergic receptor
      luciferase fusion genes. The ability of glucocorticoids to suppress luciferase
      expression was not altered when the most 5'-localized GRE was deleted. Deleting
      the potential GRE at -950, in contrast, abolished glucocorticoid-induced
      suppression of the beta 1-adrenergic receptor-luciferase gene transcription. A 25
      bp element containing the GRE sequence between nucleotides -950 and -926 confers
      glucocorticoid-dependent inhibition of transcription to a neutral promoter. Gel
      mobility shift assays with the alpha-subunit of the human glucocorticoid receptor
      (hGR alpha) expressed in reticulocyte lysates demonstrated specific binding to
      the 25-bp sequence harboring the putative GRE. We report an inhibitory GRE in the
      promoter of the rat beta 1-adrenergic receptor gene that is conserved among the
      rat, human, and mouse genes.

PMID- 9259050
TI  - Pharmacological sequestration of a chimeric beta 3/beta 2 adrenergic receptor
      occurs without a corresponding amount of receptor internalization.
AB  - Many G-protein-coupled receptors undergo sequestration (rapid loss of cell
      surface receptor binding sites) following exposure to agonists. This process has
      been assayed traditionally by the use of membrane-impermeant radioligands to
      measure cell-surface binding sites before and after exposure of cells to
      agonists. Pharmacological sequestration of the beta 2 adrenergic receptor is
      associated with internalization of the receptor protein, although it is not known
      whether receptor internalization is the only mechanism by which ligand-binding
      sites can be sequestered from the cell surface. Here we show that a chimeric
      mutant adrenergic receptor, constructed by attaching the carboxyl-terminal
      cytoplasmic domain from the beta 2 receptor to the beta 3 receptor sequence,
      exhibits agonist-induced sequestration (measured by 3H-CGP-12177 binding to
      intact human embryonal kidney [HEK] 293 cells) that is in significant excess to
      the small amount of receptor internalization measured in the same cells by
      quantitative flow cytometry. Furthermore, sequestration of the chimeric mutant
      receptor is reversible at 13 degrees C, a condition that blocks internalization
      and recycling of adrenergic receptors and has no effect on the sequestration of
      beta 2 receptors. These data suggest the operation of two distinguishable
      mechanisms of receptor sequestration in the same cells: agonist-induced
      internalization and an alternative, biochemically distinguishable mechanism that
      occurs without a corresponding amount of internalization of the receptor protein.

PMID- 9259051
TI  - Alpha 1 adrenergic receptor activation of proto-oncogene expression in arterial
      smooth muscle: regulation by nitric oxide and vascular injury.
AB  - The role of the endothelium in modulating smooth muscle cell growth is unclear.
      alpha 1 adrenergic receptors activate proto-oncogene expression in smooth muscle.
      We have now found in rat aorta that carbachol, a muscarinic cholinergic agonist
      that promotes release of nitric oxide (NO), inhibits expression of c-fos and c
      jun mRNA induced by alpha 1 receptors. NO synthase inhibitors blocked the effects
      of carbachol on c-fos mRNA and a cGMP analog mimicked carbachol. After balloon
      injury in rat aorta using in situ hybridization, the catecholamine-induced
      increase in c-fos mRNA expression in the medial layer was inhibited by the alpha
      1 receptor antagonists, prazosin and chloroethylclonidine. In the neointima, this
      response was fully blocked by prazosin; however, chloroethylclonidine only
      partially inhibited it. These results suggest that NO, acting through a cGMP
      dependent mechanism, inhibits expression of the c-fos and c-jun genes in
      arteries, which may contribute to the growth-inhibiting effects of the
      endothelium. After endothelial damage, the activation of c-fos in neointima by
      adrenergic stimulation may involve a subtype of alpha 1 receptor different from
      that utilized in medial smooth muscle.

PMID- 9259052
TI  - Occupancy and composition of proteins bound to the AP-1 sites in the
      glucocorticoid receptor and c-jun promoters after glucocorticoid treatment and in
      different cell types.
AB  - The glucocorticoid receptor (GR) and c-jun promoters both contain activator
      protein-1 (AP-1) sites (GR AP-1 site and c-jun AP-1 site, respectively) that vary
      from the consensus AP-1 site. Electrophoretic mobility shift assays (EMSAs) were
      used to monitor GR AP-1 and c-jun AP-1 oligonucleotide binding by nuclear
      extracts from AtT-20 and L929 cells that were hormone- and vehicle-treated for 1,
      6, or 24 h. Both AtT-20 and L929 cell nuclear extracts bound the c-jun AP-1 site
      somewhat better than the GRAP-1 site and, in the majority of cases, extracts from
      hormone-treated cells shifted both GRAP-1 and c-jun AP-1 oligonucleotides more
      than nontreated nuclear extracts. Supershift assays, using Jun and Fos family
      member-specific antibodies, showed that protein complexes formed by AtT-20 cell
      nuclear extracts bound to the c-jun AP-1 site were comprised of Jun family
      members, JunD, JunB, and cJun. No Fos family members were present. However,
      protein complexes from AtT-20 nuclear extracts that bound the GR AP-1 site were
      supershifted by JunD, JunB, cJun, and Fra-2 specific antibodies. In L929 cell
      nuclear extracts, the c-jun AP-1 site is bound by JunD and cJun. No clear
      association of Fos family members with the c-jun AP-1 site could be demonstrated.
      The GR AP-1 site bound protein complexes composed of JunD, JunB, Fra-2, and Fra-1
      from L929 nuclear extracts. This demonstrates that the composition of the protein
      complexes that associate with the c-jun AP-1 site differs from those that bind
      the GR AP-1 site. These data also indicate that the protein complexes that bind
      the GR and c-jun AP-1 sites are cell-type-specific. Computer analysis also
      revealed five putative cyclic AMP response elements (CREs) in the GR promoter.
      Relative mobility shift and binding studies suggest that CRE binding protein
      (CREB), CREB modulator (CREM), or CREB/CREM may be associated with the c-jun AP-1
      and/or GR AP-1 sites, but the association at these sites occurs at a lower
      binding affinity than for a consensus CRE. Nuclear extracts from AtT-20 and L929
      cells were able to shift the CRE, and supershift analysis revealed that Jun
      family members are part of the protein complexes that bind the CRE. Pan Jun and
      pan Fos antibodies were able to supershift protein-CRE complexes formed using NIH
      3T3 nuclear extracts. These data raise the possibility that the promiscuous
      binding of CREB and/or CREM to the AP-1 site, and AP-1 transcription factors to
      one or more CREs, in the GR promoter may contribute to the regulation of GR gene
      expression.

PMID- 9259054
TI  - Course of neurological recovery and cerebral prognostic signs during cardio
      pulmonary resuscitation.
AB  - The recovery of cranial nerve reflexes was evaluated sequentially in time during
      the efforts at resuscitation in 111 victims of circulatory arrest of primary
      cardiovascular or pulmonary origin. Fifty-seven patients had some brain function
      when life support was initiated (Group I) while 54 had at first no such function
      (Group II). Recovery occurred in a fixed order, irrespective of the initial
      neurological status or subsequent outcome: spontaneous respiratory movements were
      either present or were the first function to return; thereafter followed
      pupillary light reflexes, coughing-swallowing, and ciliospinal reflexes, in that
      order. Orderly recovery was featured by a time-related return of reflexes and
      consciousness while abnormal courses were characterized by stagnation of the
      recovery process, lack of time-related return of and loss of function. Prognostic
      rules were similar for the two population groups. Reflex tests at 10-60 min of
      resuscitation differentiated patients who would regain consciousness from those
      remaining unconscious with sensitivities and specificities > or = 80. A positive
      pupillary response or coughing-swallowing at 10 min, or ciliospinal reflex at 20
      min predicted return of consciousness with positive predictive values of 0.85
      1.00 (prior odds 0.29) while negative tests at 20-30 min indicated failure of
      complete recovery with values of 0.94-100 (prior odds 0.89).

PMID- 9259053
TI  - Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of
      a human pilot study.
AB  - PRIMARY OBJECTIVE: To determine if adenosine receptor antagonism has any
      beneficial impact on victims of asystolic cardiac arrest and whether or not it
      warrants further clinical study as a treatment for cardiac asystole. MATERIALS
      AND METHODS: A 6-month prospective, randomized, double-blinded, placebo
      controlled trial, set in an urban emergency medical services system, in adults
      with nontraumatic asystolic out-of-hospital cardiac arrest. Patients in whom
      standard advanced cardiac life support pharmacotherapy failed were randomized to
      receive placebo or aminophylline, a nonspecific competitive adenosine receptor
      antagonist. Rhythms were recorded before and after intervention. RESULTS: Twenty
      two patients were appropriately entered into the trial. Eight patients served as
      controls and 14 patients received aminophylline. The groups were similar in all
      measured parameters except for initial rhythm. None of the patients in the
      placebo group responded to the intervention. Half of the patients in the
      treatment group had return of organized cardiac electrical activity. CONCLUSION:
      Our results suggest that adenosine receptor antagonism may have a role in the
      treatment of cardiac asystole. Further clinical studies to validate these
      findings and clarify the appropriate use of adenosine receptor antagonists in
      cardiac asystole may be justified.

PMID- 9259055
TI  - Predicting survival, in-hospital cardiac arrests: resuscitation survival
      variables and training effectiveness.
AB  - AIM: the purpose of this study was to determine the key factors influencing
      survival from cardiopulmonary resuscitation and to analyse the effectiveness of a
      resuscitation training programme. METHOD: a prospective analysis of all
      cardiopulmonary resuscitation attempts was performed over a period of 3 years.
      Included in the study were 808 in hospital cardiac arrests, on whom a full
      cardiopulmonary resuscitation attempt was performed. Immediate, 24 h and
      discharge survival rates were the main outcome measures. RESULTS: the immediate
      survival rate was 43.2%, then 30.2% at 24 h, and 21.9% by discharge. Multivariate
      analysis of all variables showed that the key factors influencing immediate
      survival were the 'duration of the arrest', the 'primary arrhythmia', 'basic life
      support within 3 min of an arrest', 'age less than 70 years', 'the primary mode
      of arrest-respiratory or cardiac' and 'difficulties with equipment and staff
      skills during a resuscitation'. Resuscitation training over the 3 year period was
      shown to have been effective, with improved survival rates on the wards and a
      reduced number of serious difficulties at arrests. CONCLUSION: data collection
      and analysis of cardiopulmonary resuscitation attempts are essential for the
      formulation of survival indicators, and the subsequent training of resuscitation
      teams.

PMID- 9259056
TI  - Skills of lay people in checking the carotid pulse.
AB  - American Heart Association as well as European Resuscitation Council require the
      carotid pulse check to determine pulselessness in an unconscious victim and to
      decide whether or not cardiopulmonary resuscitation (CPR) should be initiated.
      Recent studies on the ability of health professionals to check the carotid pulse
      have called this diagnostic tool in question and led to discussions. To
      contribute to this discussion we performed a study to evaluate skills of lay
      people in checking the carotid pulse. A group of 449 volunteers (most had
      participated in a first aid course) were asked to check the carotid pulse in a
      young healthy, non-obese person by counting aloud the detected pulse rate. Time
      intervals until correct detection of the carotid pulse were registered. Overall
      the volunteers needed an average of 9.46 s, ranging from 1 to 70 s. Only 47.4% of
      the volunteers were able to detect a pulse within 5 s, and 73.7% within 10 s. A
      level of 95% volunteers detecting the pulse correctly was reached only after 35
      s. Based on these findings we conclude that the intervals established for carotid
      pulse check may be too short and that perhaps the value of pulse check within in
      the scope of CPR needs to be reconsidered.

PMID- 9259057
TI  - The teaching of cardiopulmonary resuscitation in schools in Hampshire.
AB  - In order to maximise the number of potential providers of cardiopulmonary
      resuscitation (CPR) in the community, it has been suggested that a programme of
      basic life support (BLS) training should be included within the school
      curriculum. Using a questionnaire sent to 275 schools in south east Hampshire
      (representing 71,716 pupils), we discovered that BLS was taught at only 26% of
      schools which replied. The age at which teaching commenced ranged from 7-16 years
      (mode = 10 years). We estimated that almost 5000 children might currently be
      trained annually in these schools. Consequently, each year approximately 40% of
      children in south east Hampshire schools might be exposed to BLS training. On
      average, schools offering BLS tuition were larger, had more teaching staff and
      employed a higher proportion of staff who were themselves BLS providers. The
      majority of BLS teaching was undertaken by school staff (50.9% of schools) and
      members of the Red Cross, The St. John Ambulance Brigade or statutory ambulance
      service (30.9%). One school utilised members of the local fire brigade. Only one
      school offering BLS training to its pupils did not have a staff member trained in
      CPR.

PMID- 9259058
TI  - Fatal pulmonary edema after nitric acid inhalation.
AB  - We report a case of acute inhalation injury of nitric acid in a 56-year old white
      male. The patient presented conscious and dyspnoic at the emergency department
      after cleaning a copper chandelier with nitric acid. He had to be intubated 2 h
      after admission and mechanically ventilated because of fulminant respiratory
      insufficiency. As all sources of mechanical ventilation failed, extracorporeal
      membrane oxygenation had to be established 7 h after admission. With the
      additional use of surfactant and low dose inhalation therapy with nitric oxide
      (NO), the patient could be stabilised for 3 days and lung function improved
      temporarily. Despite all efforts the patient died at the fourth day from
      refactory respiratory failure. Pathologic examination revealed massive pulmonary
      edema without signs of inflammation. Thus, nitric acid inhalation induced
      pulmonary edema appears to be a most severe situation in which even most modern
      therapeutic interventions fail. As, in respect of recent literature and our case
      no promising therapy for nitric acid inhalation pulmonary edema is available, our
      efforts have to be directed towards prevention of nitric acid exposure.

PMID- 9259059
TI  - Variation in defibrillation modes after synchronized cardioversion: a potential
      hazard.
AB  - We conducted a survey of all defibrillators currently on the European market that
      offer synchronized cardioversion. The mode after cardioversion can be classed
      into one of four categories: (1) remain in synchronized mode; (2) defer to
      asynchronized mode; (3) 'intelligent'; and (4) configurable. The different modes
      and the lack of standardization present a potential hazard because they cause
      confusion among the user of the defibrillator. Uniformity should be obtained
      after broad agreement between clinicians and manufacturers of defibrillators.

PMID- 9259060
TI  - Asphyxiation versus ventricular fibrillation cardiac arrest in dogs. Differences
      in cerebral resuscitation effects--a preliminary study.
AB  - We explored the hypothesis that brain damage after cardiac arrest caused by
      ventricular fibrillation (VF) needs different therapies than that after
      asphyxiation, which has been studied less thoroughly. In 67 healthy mongrel dogs
      of both sexes cardiac arrest (at normothermia) by ventricular fibrillation (no
      blood flow lasting 10 min) or asphyxiation (no blood flow lasting 7 min) was
      reversed by normothermic external cardiopulmonary resuscitation, followed by
      intermittent positive-pressure ventilation for 20 h, and intensive care to 96 h.
      To ameliorate ischemic brain damage, the calcium entry blocker lidoflazine or a
      solution of free radical scavengers (mannitol and L-methionine in dextran 40)
      plus magnesium sulphate, was given intravenously immediately upon restoration of
      spontaneous circulation. Outcome was evaluated as functional deficit, brain
      creatine kinase (CK) leakage into the cerebrospinal fluid (CSF) and brain
      morphologic changes. Lidoflazine seemed to improve cerebral outcome after VF but
      not after asphyxiation. Free radical scavengers plus magnesium sulphate seemed to
      improve cerebral outcome after asphyxiation, but not after VF. After VF,
      scattered ischemic neuronal changes in multiple brain regions dominated, and
      total brain histopathologic damage scores correlated with final neurologic
      deficit scores at 96 h (r = 0.66) and with peak CK levels in CSF (r = 0.81).
      After asphyxiation, in addition to the same ischemic neuronal changes,
      microinfarcts occurred, and there was no correlation between total brain
      histopathologic damage scores and neurologic deficit scores or CK levels in CSF.
      CONCLUSIONS: Different mechanisms of cardiac arrest, which cause different
      morphologic patterns of brain damage, may need different cerebral resuscitation
      treatments.

PMID- 9259061
TI  - Magnesium sulfate solution dramatically improves immediate recovery of rats from
      hypoxia.
AB  - This study in rats investigated the effects of 0.5 mEq/1 kg body weight of
      magnesium sulfate solution upon hypoxic left cardiac ventricular pressure (Part
      1), optimal timing for injection of magnesium sulfate solution for successful
      resuscitation (Part 2) and survival benefits of magnesium sulfate after 8 or 12
      min of hypoxia (Part 3) in rats resuscitated by single bolus arterial reperfusion
      using 2 ml of arterial blood and 6-9 micrograms epinephrine. A total of 153
      pentobarbital anesthetized rats were subjected to 8 or 12 min 0.75% O2:99.25% N2
      hypoxia in order to induce cardiac arrest. In Part 1, 13 rats (six control and
      seven injected with magnesium sulfate solution) were subjected to 12 min hypoxia
      and cardiac left ventricular pressure (LVP) was measured. In Part 2, 47 rats were
      exposed to 12 min of hypoxia. Normal saline or magnesium sulfate solution was
      injected prior to hypoxia, at 2 or 4 min of hypoxia, to find the optimal timing
      of magnesium sulfate injection for successful resuscitation by arterial
      reperfusion. In Part 3, 90 rats were studied to determine 7-day survival. Two
      control groups were injected with saline during 8 min (29 rats) or 12 min (18
      rats) of hypoxia and two groups received magnesium sulfate solution during 8 min
      (14 rats) and 12 min (29 rats) of hypoxia. Magnesium sulfate fully reversed the
      hypoxic increase of LVP and improved survival after 12 min of hypoxia from
      approximately 15 (control) to 100% if given during the first 2.5 min of hypoxia.
      The main cause of the progressive resuscitation failure after 8 or 12 min control
      hypoxia was a progressive increase in acute cardiac failure. Although magnesium
      sulfate solution significantly improved immediate recovery after hypoxia (8 and
      12 min), mortality due to reperfusion injury (para or tetraplegia) was observed
      in 62% of rats surviving longer than 1 day after 8 min and 100% after 12 min
      hypoxia (in control rats-50 and 100%, respectively). The overall survival after
      hypoxia, with or without reperfusion injury, was relatively low: 28% in control
      groups after 8 min and 17% after 12 min. In the magnesium sulfate groups these
      numbers were only slightly higher, 36 and 21%, respectively. It is concluded that
      in conjunction with arterial reperfusion magnesium sulfate infusion is very
      effective in improving acute cardiac recovery after 8-12 min of hypoxia. The
      likely mechanism of magnesium sulfate action is decreased incidence of
      ventricular fibrillation (VF) and asystole, and possibly myocardial relaxation
      during and after hypoxia, a property which may qualify MgSO4 as an ischemic
      preconditioning agent. Poor long-term survival rates of rats exposed to hypoxia
      and resuscitated by intraarterial reperfusion do not support its use in
      resuscitation.

PMID- 9259062
TI  - Effects of the AT1-selective angiotensin II antagonist, telmisartan, on
      hemodynamics and ventricular function after cardiopulmonary resuscitation in
      pigs.
AB  - The purpose of this study was to investigate the effects of the angiotensin II
      (ANG II) antagonist, telmisartan, on hemodynamics, myocardial function and
      myocardial blood flow during the postresuscitation phase in a porcine model of
      CPR and to compare these to saline. After 4 min of ventricular fibrillation and 5
      min of closed-chest CPR, defibrillation was performed in 16 domestic pigs to
      restore spontaneous circulation (ROSC). Ten minutes after ROSC, animals were
      allocated to receive either the ANG II antagonist, telmisartan, at a dose of 1
      mg/kg (n = 8) or saline (n = 8). Hemodynamics, myocardial function and myocardial
      blood flow were measured prearrest and at 5, 30, 90 and 240 min after ROSC. Using
      a Swan-Ganz catheter with a fast responding-thermistor and a micromanometer
      tipped catheter, right ventricular end-diastolic and end-systolic volume, right
      ventricular ejection fraction, left ventricular contractility were 67 +/- 6 ml
      (mean +/- S.E.M.), 42 +/- 4 ml, 38 +/- 2%, 2036 +/- 77 mmHg/s in the telmisartan
      group and 82 +/- 2 ml (P < 0.05), 59 +/- 3 ml (P < 0.01), 28 +/- 2% (P < 0.01),
      1596 +/- 82 mmHg/s (P < 0.01) in the control group, at 240 min after ROSC. No
      significant differences in mean aortic and pulmonary artery pressure, cardiac
      index or myocardial blood flow between the two groups were found. We conclude
      that the ANG II antagonist telmisartan administered during the postresuscitation
      phase in pigs increases myocardial contractility without changing cardiac index,
      systemic vascular resistance, pulmonary vascular resistance, or myocardial
      perfusion.

PMID- 9259063
TI  - Anesthetic regimen effects on a pediatric porcine model of asphyxial arrest.
AB  - The effects of three anesthetic regimens on an established model of pediatric
      porcine hypoxic-hypercarbic arrest were examined. Twenty-four preadolescent
      miniature piglets were paralyzed, mechanically ventilated and anesthetized with
      one of three regimens: IM + IV pentobarbital (n = 8); IM + IV ketamine (n = 8);
      or IM ketamine+inhaled isoflurane (n = 8). Asphyxial cardiopulmonary arrest was
      induced and, after and 8 min cardiac arrest nonintervention interval, a
      standardized protocol of manual CPR with mechanical ventilation was performed.
      Outcome variables included incidence of ventricular fibrillation, time to cardiac
      arrest, endogenous plasma epinephrine levels and arteriovenous epinephrine
      gradients. IV Ketamine anesthesia produced the highest incidence of ventricular
      fibrillation (P < 0.01 vs. pentobarbital and isoflurane). Time to asphyxia
      induced cardiac arrest was greatest for the pentobarbital group (P < 0.05 vs.
      ketamine and isoflurane). During induction of asphyxial cardiac arrest (low
      cardiac flow), endogenous venous epinephrine accumulation was highest in the
      pentobarbital anesthetized group (P < 0.05). After 8 min of untreated cardiac
      arrest and 1 min of CPR (low flow), arterial epinephrine levels were highest in
      the ketamine group (P < 0.05). Endogenous epinephrine gradients were venous >
      arterial in all groups at the end of the 8 min cardiac arrest non-intervention
      interval (no flow). After 1 min of CPR, the gradients had either equalized or
      reversed to arterial > venous in all groups except for pentobarbital. As designed
      and expected, return of spontaneous circulation did not occur in any animal. We
      conclude that, in developing models of porcine asphyxial cardiopulmonary arrest
      and resuscitation to simulate pediatric human arrest, variations in anesthetic
      regimen produce significant differences in parameters that are important to
      consider: time to asphyxia induced cardiac arrest, fibrillation threshold, plasma
      epinephrine level and arteriovenous epinephrine gradient. Anesthetic effects need
      to be carefully considered and clearly explained to facilitate the interpretation
      of studies of interventions in cardiopulmonary arrest and resuscitation.

PMID- 9259064
TI  - Epinephrine pharmacokinetics and pharmacodynamics following endotracheal
      administration in dogs: the role of volume of diluent.
AB  - OBJECTIVE: to define the optimal volume of dilution for endotracheal(ET)
      administration of epinephrine (EPI). DESIGN: prospective, randomized, laboratory
      comparison of four different volumes of dilution of endotracheal epinephrine (1,
      2, 5, and 10 ml of normal saline). SETTING: large animal research facility of a
      university medical center. SUBJECTS AND INTERVENTIONS: epinephrine (0.02 mg/kg)
      diluted with four different volumes (1, 2, 5, and 10 ml) of normal saline was
      injected into the ET tube of five anesthetized dogs. Each dog served as its own
      control and received all four volumes in different sequences at least 1 week
      apart. Arterial blood samples for plasma epinephrine concentration and blood
      gases were collected before and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 10, 15, 20, 25,
      30 and 60 min after drug administration. Heart rate and arterial blood pressure
      were continuously monitored with a polygraph recorder. MEASUREMENTS AND MAIN
      RESULTS: higher volumes of diluent (5 and 10 ml) caused a significant decrease of
      PaO2, from 147 +/- 8 to 106 +/- 10 torr, compared with the lower volumes of
      diluent (1 and 2 ml), from 136 +/- 10 to 135 +/- 7 torr (P < 0.05). These effects
      persisted for over 30 min. Mean plasma epinephrine concentrations significantly
      increased within 15 s following administration for all the volumes of diluent.
      Mean plasma epinephrine concentrations, maximal epinephrine concentration (Cmax)
      and the coefficient of absorption (Ka) were higher in the 5 and 10 ml groups. The
      time interval to reach maximal concentration (Tmax) was shorter in the 5 and 10
      ml groups. Yet these results were not significantly different. Heart rate,
      systolic and diastolic blood pressures did not differ significantly between the
      groups throughout the study. CONCLUSIONS: Dilution of endotracheal epinephrine
      into a 5 ml volume with saline optimizes drug uptake and delivery without
      adversely affecting oxygenation and ventilation.

PMID- 9259065
TI  - Active compression-decompression resuscitation: the influence of different chest
      geometries on the force transmission.
AB  - Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) is
      performed using a plunger-like suction device applied onto the chest. Forces are
      partly transferred through the center of this device as well as through the
      peripheral ring of the plunger's lip seal. We analysed the load transmission
      distribution of the Ambu CardioPump; therefore a homemade mechanical model was
      used for simulating different chest geometries. We applied compression forces up
      to 750N on the device using a 'material testing machine', and we determined the
      load transferred through the central part of the device and the peripheral ring
      respectively. The results show that the deeper the sternum is inbeded in the
      chest the more force is distributed onto the peripheral ring of the plunger's
      vacuum cup. For a simulated flat chest, 70 N was transferred through the
      peripheral ring; at a simulated sternal depression of 20 mm, more than 300 N were
      transferred peripherally. This study points out that different chest geometries
      have to be considered when using CardioPump.

PMID- 9259066
TI  - Excess mortality associated with the use of a rapid infusion system at a level 1
      trauma center.

PMID- 9259067
TI  - Ventricular standstill and cardiac percussion.

PMID- 9259068
TI  - Paediatric chain of survival.

PMID- 9259069
TI  - Guidelines for the advanced management of the airway and ventilation during
      resuscitation. A statement by the airway and ventilation management working group
      of the European Resuscitation Council, 1996 (Resuscitation 1996;31:201-230)

PMID- 9259070
TI  - Collection of uniform cardiac arrest data by ambulance services in the UK.

PMID- 9259071
TI  - Molecular biology of the Chlamydia pneumoniae surface.
AB  - Chlamydia pneumoniaeis a fastidious microorganism with a characteristic biphasic
      lifecycle causing a variety of human respiratory tract infections. There is
      limited knowledge about the molecular biology of C. pneumoniae, and only a few
      genes have been sequenced. The structure of the chlamydial surface differs from
      that of Chlamydia trachomatis. In order to study the surface of C. pneumoniae we
      generated monoclonal antibodies (MAbs) against C. pneumoniae strain VR-1310 and
      selected 14 MAbs that reacted with the surface of C. pneumoniae. All MAbs reacted
      in immunoelectron microscopy with the surface of both whole C. pneumoniae VR-1310
      elementary bodies and with purified sarcosyl extracted outer membrane complexes.
      However, only 2 of the MAbs reacted in immunoblotting with C. pneumoniae proteins
      and only with antigen that had not been heat treated in SDS-sample buffer. This
      indicates the dominance of conformational epitopes at the C. pneumoniae surface.

PMID- 9259072
TI  - Comparison of nasopharyngeal and throat swabs for the detection of Chlamydia
      pneumoniae and Mycoplasma pneumoniae by polymerase chain reaction.
AB  - Nasopharyngeal and throat swabs taken from 66 patients presenting at the
      Department of Infectious Disease with symptoms of upper and lower respiratory
      tract infection were analysed by use of the polymerase chain reaction (PCR) for
      Chlamydia pneumoniae and Mycoplasma pneumoniae. A total of 18 patients (27%) were
      positive by PCR for C. pneumoniae. All 18 patients were positive from throat
      swabs, and three were also positive from nasopharyngeal specimens. The difference
      between the outcome of PCR using throat and nasopharyngeal swabs was
      statistically significant. A total of 7 patients (10.6%) were positive for M.
      pneumoniae and of these, 6 were positive from throat swabs and 2 were positive
      from nasopharyngeal swabs. This difference was not statistically significant,
      probably due to the low numbers of positive patient specimens.

PMID- 9259073
TI  - Assay of antibiotic susceptibility of Chlamydia pneumoniae.
AB  - It is well known that treatment of Chlamydia pneumoniae infections is difficult.
      High doses and prolonged treatment is often needed to achieve clinical cure
      despite good in vitro effect of the drugs used. We here discuss different
      methodological problems in the determination of MIC and MBC values of C.
      pneumoniae. The length of the preincubation time and the lack of fluctuation of
      the antibiotic concentrations may affect the outcome of the currently used assay.

PMID- 9259074
TI  - Animal models for Chlamydia pneumoniae infection.
AB  - There is accumulating evidence that persistent Chlamydia pneumoniae infections
      occur in vivo. Animal studies are necessary in order to evaluate the effects of
      different treatment regimens for eradication of such infections. A mouse model
      was found to be efficacious for the study of the effects of cortisone and
      antimicrobial agents on C. pneumoniae infection.

PMID- 9259075
TI  - Cell mediated immunity to Chlamydia pneumoniae.
AB  - The association of Chlamydia pneumoniae to several chronic diseases such as
      atherosclerosis has been suggested serologically and by direct demonstration of
      organisms in disease lesions. Cell mediated immunity is crucial in host defense
      against intracellular pathogens such as C. pneumoniae. C. pneumoniae is a
      relatively recently recognized pathogen and the cellular mechanisms in C.
      pneumoniae immunity have so far remained unstudied. The present review includes
      the data available on C. pneumoniae proteins and their role as T cell activating
      antigens and Th1/Th2 balance in C. pneumoniae immunity.

PMID- 9259076
TI  - Epidemic patterns and carriage of Chlamydia pneumoniae in Norway.
AB  - Chlamydia pneumoniae infection, in earlier days misdiagnosed as ornithosis, is
      very common in Norway. The disease develops slowly, a feature that may account
      for the very large number of subclinical cases, which may be seven fold more
      common than clinical cases. Subclinical cases produce an antibody response
      similar to that seen in overt clinical disease. Silent carriage of C. pneumoniae
      in healthy individuals may be frequent. Therapy based on positive cell culture or
      polymerase chain reaction (PCR) in the absence of pneumonic symptoms may be
      questionable. PCR has, however, given the slow development of disease, revealed
      itself as a handy epidemiological technique useful for the survey of healthy
      populations.

PMID- 9259077
TI  - Respiratory tract infection due to Chlamydia pneumoniae in military personnel.
AB  - The objective of this investigation was to determine whether Chlamydia pneumoniae
      was involved in an outbreak of respiratory disease among military recruits, 92
      patients (average age 20.1 years) were included in the study if they had a sore
      throat or cough for more than 1 week. In addition to sore throat and cough,
      fatigue, headache, dyspnoea and vertigo were the most frequent symptoms. The
      patients received standard treatment with 100 mg of doxycycline b.i.d. for 14
      days. In 38.8% of cases symptoms were alleviated after 1-2 weeks of treatment,
      and in 22.4% of cases after 2-3 weeks of treatment. Pretreatment throat washings
      and sera were sampled for Chlamydia. Sera were drawn for Chlamydia, Mycoplasma
      and adenovirus serology. Cell culture (Hep-2) and 3 different serological methods
      microimmunofluorescence (MIF), enzyme immunoassay with a recombinant
      glycoconjugate antigen (r-EIA) and immunoperoxidase assay (IPA)-were used. Cell
      culture was found to have too low a sensitivity to be of diagnostic value. Acute
      infection was demonstrated in 13% by MIF IgM and in an additional 21% by MIF IgG
      (titre rises). Enzyme immunoassay IgM was found in 17% and IPA IgM in 19% of
      individuals without MIF IgM antibodies. Microimmunofluorescence was found to be
      the most useful test for serodiagnosis. The combination of serological methods
      showed that 40 out of 52 (76.9%) had an acute infection with possible chlamydial
      aetiology. In conclusion, methodological improvements are necessary for the
      aetiological diagnosis of chlamydial respiratory infections.

PMID- 9259078
TI  - Respiratory Chlamydial infections in a Hong Kong teaching hospital and
      association with coronary heart disease.
AB  - The microimmunofluorescence antibody technique was used to determine the
      seroprevalence of antibodies to Chlamydia pneumoniae and Chlamydia psittaci from
      hospitalized patients in Hong Kong. Antibodies to C. pneumoniae were found in
      54.8% of 157 patients hospitalized with respiratory disease, in 71.1% of 83
      patients with cardiac disease and in 31.2% of 93 patients without either
      respiratory or cardiac disease. Antibodies to C. psittaci were found in 0.9% of
      the combined study groups. There was serological evidence of C. pneumoniae being
      the responsible agent in 24.8% of the severe respiratory cases. A significant
      correlation between antibody prevalence and coronary heart disease was identified
      during the study.

PMID- 9259079
TI  - Chlamydia pneumoniae and chronic lung diseases.
AB  - Chlamydia pneumoniae infection has been implicated in several chronic lung
      diseases by serology and direct antigen detection. Acute lower respiratory tract
      infection caused by C. pneumoniae seems often to precede attacks of asthma in
      both children and adults. Chlamydia pneumoniae is also involved in some
      exacerbations of chronic bronchitis and chronic obstructive lung disease but,
      more importantly, seems to be strongly associated with the latter irrespective of
      exacerbation status. Moreover, persistently elevated C. pneumoniae antibody
      titres have been observed in sarcoidosis and lung cancer.

PMID- 9259080
TI  - Reinfection with Chlamydia pneumoniae may induce isolated and systemic vasculitis
      in small and large vessels.
AB  - It is a common clinical experience that the onset of the so called non infectious
      vasculitides is often preceded by upper respiratory tract symptoms. A specific
      agent is only occasionally recovered. We report five cases in Sweden with
      manifestations of vasculitis from different organs. In three of the five patients
      the onset was preceded by upper respiratory tract symptoms. All patients had
      serologic findings indicating Chlamydia pneumoniae infection and all required
      corticosteroid treatment for symptomatic recovery. One was diagnosed as an
      aseptic meningitis. Another was diagnosed as a cerebral arteritis, probably a
      variant of a giant cell arteritis. A third patient had symptoms similar to a
      polymyalgia rheumatica engaging the thighs. Two patients had an acute myocardial
      infarction. One of them had Cogan's syndrome. The other also had pulmonary and
      hepatic engagement and an elevated level of anti basement membrane IgM
      antibodies, though not to the Goodpasture antigen. He had no renal involvement.
      The diagnosis of Chlamydia pneumoniae infection was based on the detection of
      species-specific IgA, IgG and IgM antibodies to Chlamydia pneumoniae using
      microimmunofluorescence technique, MIF. Four of the 5 cases exhibited a fourfold
      increase in antibody titers, and the fifth case was found to have high levels of
      IgG and IgA antibodies, suggesting recent infection. Investigations for other
      infectious agents were negative in all patients. The serologic findings in those
      patients are consistent with a pattern of reinfection with Chlamydia pneumoniae.
      We therefore suggest that reinfection with Chlamydia pneumoniae may induce
      isolated and systemic vasculitis in virtually any organ of the body.

PMID- 9259081
TI  - Interaction between infection and exercise with special reference to myocarditis
      and the increased frequency of sudden deaths among young Swedish orienteers 1979
      92.
AB  - Infection and fever evoke a cytokine-mediated host response resulting in negative
      nitrogen balance, muscle protein degradation, which includes the skeletal muscles
      as well as the heart muscle, and deteriorated muscle function. Physical training
      has an opposite effect. Moderate physical training also stimulates the immune
      system, whereas exhaustive and longlasting exercise is followed by a temporary
      immunodeficiency and an increased susceptibility to respiratory tract infections.
      Exercise in the acute phase of an infection may promote complications including
      myocarditis. Exercise in myocarditis is associated with increased organism
      associated as well as immune mediated tissue damage. An increased sudden death
      (SUD) rate among young Swedish male orienteers existed in 1979-92, suggesting (a)
      common underlying cause(s). Myocarditis was one of the most conspicuous
      histopathological features. Chlamydia pneumoniae, or a similar organism cross
      reacting in diagnostic tests, is hypothesized to be a factor causing this
      increased death rate. High frequency of intense exercise sessions, which was a
      common practice among the deceased, may have been immunosuppressive, promoting
      the development of severe myocardial disease.

PMID- 9259082
TI  - Chlamydia pneumoniae and myocarditis.
AB  - Sera from 20 male patients with a diagnosis suggestive of myocarditis,
      perimyocarditis or pericarditis were found significantly more often to have
      specific IgA antibodies to Chlamydia pneumoniae than sera from healthy blood
      donors of the same age and from the same time period. A less pronounced
      difference in IgG titres was found between patients and blood donors, and IgM
      antibodies were found only in one patient. A striking variation over time in the
      prevalence of specific antibodies to C. pneumoniae was seen in consecutive male
      blood donors over a 5-year observation period. The findings were discussed and it
      was concluded that C. pneumoniae may be associated with inflammatory heart
      disease.

PMID- 9259083
TI  - Chlamydia pneumoniae and atherosclerosis--an update.
AB  - The role of Chlamydia pneumoniae in atherosclerosis is at present controversial
      and neglected by researchers studying the pathogenesis of the disease. Numerous
      seroepidemiological studies have shown an association of C. pneumoniae infection
      with coronary heart disease and recent studies have indicated the ubiquitous
      presence of C. pneumoniae in the atherosclerotic lesions. The majority of
      cardiologists are, as yet, more apt to consider the finding of C. pneumoniae in
      atherosclerotic lesions as benign particles deposited from the circulation into
      preformed lesions rather than as a known pathogenic Gram-negative bacterium
      participating in or initiating an inflammatory process. The latter possibility
      would result in the oxidation of lipoproteins and the induction of cytokines and
      proteolytic enzyme production. These phenomena are typical for atherosclerosis.
      Chlamydia are amenable for treatment with antibiotics, and the therapeutic
      importance of the verification of bacterial involvement could be significant.

PMID- 9259085
TI  - Bladder cancer: natural history, tumor markers, and early detection strategies.
AB  - Transitional cell bladder carcinoma is characterized by a dichotomous,
      multichronotopic natural history. Low and moderate grade Ta lesions frequently
      recur, yet rarely invade, and carry an excellent prognosis with currently
      available treatments. High grade Ta lesions, tumors with lamina propria invasion
      (T1), and carcinoma in situ often progress to invasive disease, at which time
      overall prognosis is significantly decreased, despite various treatment
      alternatives. Although early detection of bladder tumors, prior to muscle
      invasion, should vastly improve our ability to save both bladders and lives,
      current methods of detection are neither sufficiently sensitive nor specific.
      Tumor marker analysis is an exciting new frontier in bladder cancer evaluation,
      and may have important applications to early detection strategies, in combination
      with simple hematuria testing and other selected noninvasive screening methods.

PMID- 9259084
TI  - Epidemiology and etiology of bladder cancer.
AB  - The incidence of bladder cancer continues to increase, with an estimated 53,000
      new cases diagnosed in the United States in 1996-90% of which are transitional
      cell carcinomas. The male-to-female ratio is 3:1. A number of etiological factors
      are associated with the development of bladder cancer, but in industrialized
      countries, cigarette smoking is the most important. Specific chemicals have also
      been identified as causing bladder cancer, as have a number of occupational
      exposures to less well-defined specific agents. Treatment with cytostatic drugs,
      especially cyclophosphamide, is associated with increased risk of bladder cancer,
      as is treatment with radiotherapy for uterine cancer. In developing countries,
      especially in the Middle East and parts of Africa, infections with members of the
      genus Schistosoma are responsible for a high incidence of bladder cancer-75% of
      which are squamous cell carcinomas. Arsenic has been indicated as a bladder
      carcinogen in Argentina, Chile, and Taiwan. The reason for the high incidence of
      urinary tract cancer in individuals suffering from Balkan nephropathy has yet to
      be determined. A careful history of patients with bladder cancer is an important
      and useful process in helping to identify causal factor and, in more than one
      half the cases, a known relationship is found. Bladder cancer is a potentially
      preventable disease, with a significant morbidity and mortality in many parts of
      the world.

PMID- 9259086
TI  - Pathology of transitional cell carcinoma of the bladder and its clinical
      implications.
AB  - Transitional cell carcinomas are divided into superficial and muscle-invasive
      tumors. Most of them are superficial tumors, and approximately 15-20% are muscle
      invasive carcinomas. Pathologists play a significant role in diagnosing bladder
      tumors and in reporting features important for determining prognosis. We will
      review the cytologic and histopathologic features that help determine prognosis,
      including depth of invasion, tumor grade, multicentricity, tumor size, and the
      presence of vascular/lymphatic invasion, blood group antigen expression,
      proliferative indices, and molecular markers. Brief mention will be made of
      specimen handling, interpretation, reporting, and histologic variants of
      transitional cell carcinoma.

PMID- 9259087
TI  - Genetic studies and molecular markers of bladder cancer.
AB  - Target genes implicated in cellular transformation and tumor progression have
      been divided into two categories: proto-oncogenes which, when activated, become
      dominant events characterized by the gain of function, and tumor suppressor genes
      which become recessive events characterized by the loss of function. Alterations
      in proto-oncogenes and tumor suppressor genes seem equally prevalent among human
      cancers. Multiple mutations appear to be required to conform the malignant
      phenotype. Proto-oncogenes are activated mainly by point mutations; however,
      amplification and translocation events are also common. Tumor suppressor genes
      are inactivated by an allelic loss followed by a point mutation of the remaining
      allele. The prototype suppressor genes are the retinoblastoma (RB) gene and the
      TP53 (also known as p53) genes. Recent studies have shown that inactivation of
      TP53 and RB occur in bladder tumors that have a more aggressive clinical outcome
      and poor prognosis. We will review the molecular abnormalities associated with
      both oncogenes and tumor suppressor genes in bladder tumors, and also discuss the
      potential clinical use of their detection. The implementation of objective
      predictive assays to identify these alterations in clinical material will enhance
      our ability to assess tumor biological activities and to design effective
      treatment regimes.

PMID- 9259088
TI  - Surgical management of superficial bladder cancer (stages Ta/T1/CIS).
AB  - Transurethral surgery is the primary treatment for patients with superficial
      bladder cancer. Either electrical or laser thermal destruction is used most often
      but there is no proven therapeutic benefit for one method over the other.
      Treatment failure is usually a consequence of new tumor occurrence rather than
      the failure to eradicate existing visible tumors. Adjuvant intravesical
      chemotherapy or immunotherapy improves results over surgery alone in most
      circumstances.

PMID- 9259089
TI  - Treatment of superficial bladder cancer with intravesical chemotherapy.
AB  - Proper care of patients with superficial bladder cancer requires the assessment
      of multiple factors, including an understanding of the natural history of this
      disease, accurate clinical staging, and the expected efficacy of each drug. The
      pharmacology of intravesical mytomycin C is discussed in detail, as many of this
      drug's pharmacological principles are applicable to all intravesical
      chemotherapeutic agents, including doxorubicin, thiotepa, bacillus Calmette
      Guerin, epirubicin, and ethoglucid. The bladder wall, bladder cavity, chemical
      properties of intravesical chemotherapeutic agents, and tumor considerations are
      discussed. Suggestions based on pharmacological studies are presented to optimize
      the efficacy of intravesical chemotherapy.

PMID- 9259090
TI  - Immunotherapy of bladder cancer.
AB  - Intravesical therapy has been used in the management of superficial transitional
      cell carcinoma (TCC) of the urinary bladder (i.e., Ta, Tl, and carcinoma in situ)
      with specific objectives which include treating existing/residual tumor,
      preventing recurrence of tumor, preventing disease progression, and prolonging
      survival. The initial clinical stage and grade remain the main determinant
      factors in survival irrespective of the treatment. Presently, bacillus Calmette
      Guerin (BCG) immunotherapy remains the most effective treatment and prophylaxis
      for TCC (Ta, Tl, CIS) and has positive outcomes on tumor recurrence rate, disease
      progression, and prolongation of survival. Prostatic urethral mucosal involvement
      with bladder cancer can be effectively treated with BCG intravesical
      immunotherapy-it has demonstrated a reduction in tumor recurrence rates, but has
      had no positive impact on disease progression or prolongation of survival.
      Interferons, keyhole-limpet hemocyanin (KLH), bropirimine, and PHOTOFRIN
      photodynamic therapy (PDT) are under investigation in the management of TCC and
      early results are encouraging. This comprehensive review highlights recent
      developments in intravesical therapy of bladder cancer and summarizes the
      mechanisms of action of BCG, and the important role of intravesical BCG
      immunotherapy and other immunotherapeutic agents in the therapy and prophylaxis
      of superficial TCC of the urinary bladder.

PMID- 9259091
TI  - Cystectomy and urinary diversion.
AB  - New insights into bladder cancer mechanisms have not yet produced clinical
      benefit. Without novel treatments, cystectomy remains the most effective local
      treatment, albeit the most aggressive. Uncertainty about the natural history of
      bladder cancer, the progression rate after other treatments, the risks of
      cystectomy and subsequent quality of life, foster debate about the indications
      for cystectomy. There are numerous urinary diversions and bladder substitutes.
      Differences in tumour extent, patient age, performance status, renal and mental
      function, and acceptance make different diversion techniques necessary.
      Urologists need not know every technique, but should know at least one technique
      of each class: an incontinent diversion (such as the ileal conduit),
      ureterosigmoidostomy, continent reservoir, and orthotopic bladder substitute. The
      common principles, advantages, and contraindications of these techniques are
      discussed.

PMID- 9259092
TI  - Treatment strategies using transurethral surgery, chemotherapy, and radiation
      therapy with selection that safely allows bladder conservation for invasive
      bladder cancer.
AB  - Combined modality therapy with the goal of effecting cure and achieving organ
      preservation has become the standard oncological approach in many malignancies.
      Although radical cystectomy has been considered the standard treatment for
      invasive carcinoma of the bladder, equivalent results have been achieved using
      combined modality treatment in selected patients, particularly those with T2 and
      T3a disease without obstructed ureters. Effective combined modality treatment
      consists of three treatment modalities: (1) transurethral resection of the
      bladder tumor (TURBT), followed by concurrent (2) chemotherapy, and (3)
      radiation. Following induction therapy, histologic response is evaluated by
      cystoscopy and biopsy. Clinical complete responders continue with concurrent
      chemotherapy and irradiation. Those patients not achieving a clinical complete
      response are advised to undergo cystectomy. Individually the local monotherapies
      of radiation, TURBT, or systemic chemotherapy each achieve a local control rate
      of 20% to 40%. When they are combined, complete response rates of 70-80% are
      achieved and 85% of these will remain free of invasive recurrence in the bladder.
      Bladder preservation trials using combined modality treatment approaches with
      selection for organ conservation by response to initial treatment report an
      overall 5-year survival rate of approximately 50%, and they have achieved a 40%
      to 45% 5-year survival rate with the bladder intact. Modern multi-modality
      bladder preservation approaches offer survival rates similar to radical
      cystectomy, for patients of similar clinical stage and age, and an improved
      quality of life by allowing a majority of patients to retain their own fully
      functional bladder. Bladder conservation therapy may be offered to selected
      patients with bladder cancer as one alternative to radical cystectomy, and its
      use should be by experienced multi-modality teams of urologic oncologists.

PMID- 9259094
TI  - Future therapies for the treatment of bladder neoplasms.
AB  - The last several decades have witnessed an exponential growth in the
      understanding of the biology of human neoplasms. As a consequence, a number of
      new strategies for the treatment of urologic cancers are currently under
      evaluation. We provide an overview of promising new treatment approaches as they
      apply to the management of transitional cell carcinoma of the urinary bladder.

PMID- 9259095
TI  - A radiologist's guide to the imaging in the diagnosis and treatment of
      developmental dysplasia of the hip. I. General considerations, physical
      examination as applied to real-time sonography and radiography.
AB  - Developmental dysplasia of the hip (DDH) has a broad spectrum of presentation
      with the minor findings resolving spontaneously and the most severe ones
      resulting in disability, if not diagnosed early in life. Diagnosis in the first
      few months of life allows conservative treatment with complete resolution in most
      cases. Suspicion of DDH is based on ethnic, family, and pregnancy history, and on
      physical examination of the newborn. Imaging assists in the diagnosis and follows
      the treatment. Different modalities have their own advantages and disadvantages.
      This article deals with the description of the disease, risk factors, statistics,
      the physical examination as applied to real-time sonography, and imaging (plain
      radiography, arthrography, computed tomography, and magnetic resonance imaging.

PMID- 9259096
TI  - Degenerative joint disease: cartilage or vascular disease?
AB  - The aetiology of degenerative joint disease is multifactorial, but one main cause
      is overloading (mechanical stress). While until recently it was well accepted
      that this represented primarily a disorder of cartilage with reactive subchondral
      changes, there is now some evidence that it might be primarily a subchondral
      problem with secondary changes in the articular cartilage. Early subchondral
      changes include redistribution of blood supply with marrow hypertension, oedema
      and probably micro-necrosis. These findings are very similar to those in
      avascular necrosis of bone and raise the question of a vascular aetiology. While
      these first reports need further proof, it seems clear that the articular
      cartilage and subchondral regions are one functional unit, in which the
      subchondral region is more stress sensitive. Recently described channels
      connecting these two regions strengthen this opinion. These new concepts are
      exciting and may make a major impact in the near future on the management of and
      research into degenerative joint disease.

PMID- 9259093
TI  - Systemic chemotherapy of transitional cell carcinoma of the urothelium.
AB  - Although the incidence of bladder cancer has increased in recent years, survival
      has also improved. Chemotherapy has made a substantial impact on this disease and
      now is used in patients with advanced or metastatic disease as well as in select
      patients with high-risk muscle invasive disease. While cisplatin remains the most
      active single antineoplastic agent, several other agents including methotrexate,
      vinblastine, and Adriamycin (doxorubicin) have important activity. More recently,
      paclitaxel and gemcitabine have shown promising activity in bladder cancer.
      Multidrug combination therapy has provided more frequent and durable responses
      than single agent therapy. Regimens containing cisplatin and methotrexate have
      been shown to be most effective in the treatment of advanced disease. Adjuvant
      chemotherapy regimes typically have included cisplatin or cisplatin and
      methotrexate combinations. However, studies have been limited and further
      prospective trials are required to determine the role of adjuvant chemotherapy.
      Multiple studies have investigated neoadjuvant chemotherapy with cisplatin and
      methotrexate combinations or anthracycline-based regimens, but study results are
      mixed. Further trials will be required to define the role of neoadjuvant
      chemotherapy in bladder cancer.

PMID- 9259097
TI  - Imaging of vascularized fibular grafts in large bone reconstruction in skeletally
      immature patients.
AB  - OBJECTIVE: To describe the imaging findings of vascularized fibular grafts (VFG)
      in large bone reconstruction in children and teenagers. DESIGN AND PATIENTS:
      Fifteen patients aged from 4 to 19 years underwent VFG for bone reconstruction
      for primary tumors involving bone in 13 cases and for chronic osteomyelitis in 2
      cases. Lesions were located in the femur (6 cases), the tibia (6 cases), the
      humerus, the distal fibula and the ilium. Radiographic follow-up was performed in
      all patients, radionuclide studies in 12 patients and MRI in 8. RESULTS: Plain
      films showed a lamellated periosteal reaction on the VFG within 3 weeks following
      the procedure in all cases. Fusion of VFG and host bone occurred during the first
      3 months. Radionuclide uptake of the VFG was seen in all cases but one. MRI
      showed cortical thickening and conservation of the high signal intensity of fatty
      marrow on T1-weighted sequences, and periosteal enhancement on dynamic post
      contrast studies in all but one of the patients. CONCLUSION: Radionuclide studies
      and MRI show the periosteal enhancement and assess the viability of the VFG
      satisfactorily. However, we feel that plain films may be sufficient to ascertain
      this viability.

PMID- 9259098
TI  - Tunnel placement in anterior cruciate ligament reconstruction: MRI analysis as an
      important factor in the radiological report.
AB  - OBJECTIVE: Correct placement of tunnels for anterior cruciate ligament (ACL)
      reconstruction is of prime importance for the clinical outcome of the patient. In
      this study, the possibility of using MRI to document tunnel placement and provide
      a more comprehensive report following ACL reconstruction was explored at no
      additional cost in patients scheduled for routine knee MRI DESIGN AND PATIENTS:
      One year after ACL reconstruction, 45 patients underwent clinical examination
      (IKCD score), radiographic examination, and MRI using a 1.5-T unit. RESULTS:
      Twenty patients with good tibial and femoral attachment results were found at
      clinical examination to have a stable knee joint with a full range of motion. In
      25 patients with suboptimal placements, examination showed either a stable knee
      with a decreased range of motion or instability with a normal range of motion.
      CONCLUSION: Patients' clinical outcome, and the radiographic and MRI findings,
      correlated closely with the quality of operative tunnel placement. A record of
      this finding is important for completeness of the radiological report.
      Furthermore the MRI findings can be used to improve the surgical quality of
      tunnel placement. Because tunnel placement can be shown adequately with
      radiography, however, MRI cannot be justified for this reason alone, so such
      assessment is advised only when MRI is needed to show all postoperative features.

PMID- 9259099
TI  - MRI gadolinium enhancement of bone marrow: age-related changes in normals and in
      diffuse neoplastic infiltration.
AB  - OBJECTIVE: To quantify gadolinium-related enhancement in the bone marrow of the
      spine in normals and in patients with homogeneous diffuse malignant bone marrow
      infiltration. DESIGN AND PATIENTS: The patients consisted of two groups: group 1
      comprised 94 healthy adults (18-86 years) without bone marrow disease and group 2
      comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration
      due to myeloma (n = 20) or breast carcinoma (n = 10). All patients received
      intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre-
      and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images
      (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the
      percentage SI increase was calculated. The results were confirmed by bone marrow
      biopsy (n = 20) and clinical parameters (n = 10). Dynamic contrast-enhanced
      studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/alpha: 68
      ms/6 ms 75 degrees) were performed in 10 controls with normal bone marrow.
      RESULTS AND CONCLUSION: Contrast material enhancement in healthy persons can vary
      greatly (range 3-59%, mean 21%, SD 11%). With increasing age there is a
      significant decrease in contrast enhancement (Pearson's correlation, P < 0.01).
      The percentage SI increase in patients with intermediate-grade (biopsy 20-50
      vol%) and high-grade (biopsy > 50 vol%) diffuse malignant bone marrow
      infiltration was significantly higher than in normals (mean 67%, SD 34%, P <
      0.001). Low-grade (biopsy < 20 vol%) diffuse malignant bone marrow infiltration
      can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application.
      In conclusion, contrast material enhancement in healthy persons can vary greatly
      and is dependent on age, while intermediate-grade and high-grade diffuse
      malignant bone marrow infiltration can be objectively assessed with SI
      measurements.

PMID- 9259100
TI  - Computed tomography of sternoclavicular joint lesions in spondylarthropathies.
AB  - To evaluate the computed tomography (CT) findings of inflammatory lesions of the
      sternoclavicular joints (SCJ) in spondylarthropathies. DESIGN AND PATIENTS: CT
      scans of the SCJs were obtained in 23 patients (group 1) with inflammatory SCJ
      lesions in spondylarthropathies. These scans were reviewed by four readers and
      compared with the CT scans of 23 matched controls (group 2). Each reader had to
      complete a 27-item grid. RESULTS AND CONCLUSION: In the 23 patients of group 1,
      the mean number of observed signs was 5.3 +/- 4.2 higher (P < 0.01) than in the
      group of 23 matched controls (2.4 +/- 1.6). Four signs were more frequently
      observed (P < 0.05) in group 1: surrounded subchondral clavicular erosions and
      cysts, surrounded subchondral sternal cysts and sternal bone sclerosis. A cyst
      and/or an erosion was associated with hyperostosis and/or bone sclerosis in 9 of
      23 patients in group 1. This association was not observed in group 2; the
      difference was significant (P < 0.001). A cyst and/or an erosive lesion was
      observed 18 times in group 1 versus 11 times in group 2; the difference was
      significant (P < 0.05). Conversely, signs of degenerative lesions (osteophytes,
      subchondral sclerosis, unevenness of joint surface) were no more frequently
      observed in controls than in group 1. This study emphasizes the diagnostic value
      of CT, in particular in the identification of inflammatory lesions, even when pre
      existing degenerative disease is present.

PMID- 9259102
TI  - Hemodialysis-related amyloidosis of the sternoclavicular joint.
AB  - Amyloid deposition is an important cause of morbidity in long-term hemodialysis
      patients, but it has rarely been reported in the sternoclavicular joint, where
      the clinical picture may be consistent with an infection. The imaging features of
      one case are discussed. Biopsy with specific staining for the beta-2
      microglobulin component of amyloid should be considered in the work up of a
      lesion of this joint in this clinical setting.

PMID- 9259101
TI  - Meniscal position on routine MR imaging of the knee.
AB  - OBJECTIVE: To determine the prevalence of meniscal protrusion (i.e. location of
      the outer edge of a meniscus beyond the tibial articular surface), and to
      determine its relationship with internal derangement, joint effusion, and
      degenerative arthropathy. DESIGN AND PATIENTS: Sagittal and coronal MR images of
      111 abnormal and 46 normal knees were evaluated for the presence of meniscal
      protrusion. We set 25% as the minimum amount of displacement considered abnormal
      because this was the smallest amount of displacement we could confidently
      discern. Presence of meniscal tear, anterior cruciate ligament (ACL) injury,
      joint effusion, or osteophytosis was also recorded. RESULTS AND CONCLUSION:
      Normal examinations demonstrated protrusion of the medial meniscus in 6.5% of
      sagittal images and 15% of coronal images, and of the lateral meniscus in 2% and
      13%, respectively. Fisher's exact test demonstrated a statistically significant
      difference between the normal and abnormal groups for the medial meniscus on both
      sagittal (P < 0.0001) and coronal (P = 0.01) images, but not for the lateral
      meniscus in either plane (P > 0.2). A protruding medial meniscus was associated
      with effusion and osteophytosis (P < 0.05) but not with meniscal or ACL tear (P >
      0.1). Posterior protrusion of the lateral meniscus was only associated with ACL
      injury (P < 0.0001); protruding anterior horns and bodies of lateral menisci were
      not associated with any of the four abnormalities. It is concluded that the
      medial meniscus may occasionally protrude more than 25% of its width, but
      protrusion is more often due to effusion and osteophytes. Protrusion of the
      posterior horn of the lateral meniscus is associated with ACL insufficiency,
      while protrusion of the body and anterior horn of the lateral meniscus is a
      normal variant.

PMID- 9259103
TI  - Sternal abscess due to Bartonella (Rochalimaea) henselae in a renal transplant
      patient.
AB  - Bartonella henselae, previously called Rochalimaea henselae, is the causative
      agent of cat scratch disease (CSD) in immunocompetent subjects and bacillary
      angiomatosis in immunocompromised ones. Bone lesions are common in bacillary
      angiomatosis, but not in CSD. We present the case of a patient with a renal
      transplant treated by immunosuppressive therapy who developed a sternal abscess
      with a histological pattern of CSD. The CT pattern was that of a lytic bone
      lesion with adjacent fluid collection. The diagnosis was made on the basis of a
      polymerase chain reaction amplification performed on bone material. Bartonella
      henselae is a newly described bacteria that causes CSD in a normal host and
      bacillary angiomatosis in immunocompromised patients. We report a case of an
      osteolytic lesions of the sternum with adjacent fluid collection related to CSD,
      which occurred in a patient with a renal transplant.

PMID- 9259104
TI  - Osteoblastic metastases from breast carcinoma with false-negative bone scan.
AB  - The authors report a case of metastatic breast carcinoma that on investigation
      was shown to have a negative bone scan in spite of multiple densely sclerotic
      metastases on radiography and CT and a positive bone biopsy. The literature is
      reviewed with regard to the subject of negative bone scans in this situation.

PMID- 9259105
TI  - Pubic osteolysis mimicking a malignant lesion: report a case with a fracture
      dislocation of the sacroiliac joint.
AB  - We report the case of a 67-year-old woman who presented to our institution with
      osteoblastic and osteolytic lesions of the pubis and fracture dislocation of the
      left sacroiliac joint. She had presented 7 months earlier to an outside
      institution with a left gluteal mass, which had been biopsied and had been
      believed to represent malignancy. A second biopsy at our institution showed no
      evidence of malignancy and was felt to represent fracture healing. A diagnosis of
      public osteolysis was made based on the radiographic and histologic findings. A
      follow-up radiograph 6 years after presentation revealed healing of the lesions,
      confirming its benignity.

PMID- 9259106
TI  - Angiomyoma of the lower extremity: MR findings.

PMID- 9259107
TI  - Tumor necrosis factor alpha is involved in the induction of plasminogen activator
      inhibitor-1 by endotoxin.
AB  - Treatment with endotoxin leads to a rise in plasminogen activator inhibitor-1
      (PAI-1) both in vivo and in vitro. Although a recent study insists that
      inhibition of tumor necrosis factor alpha (TNF alpha) does not reduce the
      induction of PAI-1 by endotoxin in rats, we imagine that TNF alpha is involved in
      the induction of PAI-1 by endotoxin, because endotoxin treatment induces TNF
      alpha and administration of TNF alpha induces PAI-1 both in vitro and in vivo. In
      order to confirm this hypothesis, we have measured plasma PAI activity and PAI-1
      mRNA in liver after endotoxin treatment with or without pretreatment by
      polyclonal rabbit antiserum against murine TNF alpha. Chronically cannulated
      Sprague-Dawley rats received intravenous injection of endotoxin (10
      micrograms/kg) 10 min after administration of anti-TNF alpha antibody (Antibody
      Group) or same volume of control rabbit serum (Control Group). PAI activity was
      measured by Coatest PAI, and PAI-1 mRNA was measured semi-quantitatively by high
      performance liquid chromatography after reverse transcription and polymerase
      chain reaction. Increases in PAI activity 4 h after endotoxin treatment were
      significantly smaller in the Antibody Group than in the Control Group, while
      increases in PAI-1 mRNA were significantly smaller at 2 h in the Antibody Group.
      These results suggest that TNF alpha is responsible, at least in part, for the
      induction of PAI-1 by endotoxin in vivo.

PMID- 9259108
TI  - Degradation of human factor XIII by lonomin V, a purified fraction of Lonomia
      achelous caterpillar venom.
AB  - Lonomia achelous caterpillar venom (LACV) causes a severe bleeding diathesis in
      humans. A constant finding in these cases is a profound depression of blood
      clotting Factor XIII (FXIII) activity. The molecular mechanisms by which LONOMIN
      V (a chromatographically purified fraction from LACV) alters the FXIII complex is
      the subject of the present study. Incubation of human purified FXIII with Lonomin
      V shows that both the zymogen and the activated forms of FXIII were
      proteolytically degraded, with the generation of peptidic fragments of low
      molecular weight. Both the A and B subunits of FXIII were degraded in a
      progressive, dose dependent manner. The B subunit was more resistant to the
      action of Lonomin V, requiring higher concentrations in order to achieve complete
      degradation. On the basis of these findings we postulate that the proteolysis of
      FXIII in vivo is one of the pathophysiological factors behind this bleeding
      syndrome.

PMID- 9259109
TI  - Platelet aggregation in patients bitten by the Brazilian snake Bothrops jararaca.
AB  - Patients bitten by the lancehead snake Bothrops jararaca usually develop systemic
      bleeding. Our aim was to evaluate platelet function in whole blood of 17 human
      patients bitten by this snake in Sao Paulo State, Brazil. Bleeding occurred in
      71% of these patients, and thrombocytopenia in 53% of them. On admission, most of
      the patients presented with hypoaggregation to 50 microM ADP and 1.2 mg/ml
      ristocetin, and only 35% of them to 5 micrograms/ml collagen. Abnormal plasma
      levels of fibrinogen and fibrin(ogen) degradation products (FDP/fdp) were also
      observed. Twenty-four hours of finishing serumtherapy, bleeding had already
      ceased, fibrinogen and FDP/fdp levels returned to hemostatic levels, and values
      for platelet aggregation returned to the reference range of controls, except for
      ADP that still remained decreased. These findings evidence that disturbances of
      platelet function are also an important factor for the development of bleeding in
      Bothrops envenomation, as well as other known hemostatic disturbances that occur
      concomitantly.

PMID- 9259110
TI  - In vitro studies on the effect of activated protein C on platelet activation and
      thrombin generation.
AB  - The effect of activated protein C (APC) on agonist-induced platelet activation
      and on thrombin generation after intrinsic (IA) and extrinsic (EA) activation of
      the coagulation system was studied by flow cytometry and by measuring levels of
      prothrombin fragment F1+2. In platelet activation studies blood drawn from
      healthy volunteers was anticoagulated with 10 micrograms/ml APC and incubated at
      37 degrees C either with saline, recombinant tissue factor (r-TF), arachidonic
      acid (AA), ADP or collagen. At definite times aliquots were taken and processed
      for flow studies. Platelet activation was measured using fluorescent monoclonal
      antibodies to platelet surface receptors GPIIIa (CD-61) and P-selectin (CD-62).
      Flow cytometric analysis showed platelet activation after all agonists used. APC
      did not influence AA-, ADP- and collagen-induced platelet activation but
      completely inhibited activation of platelets induced by r-TF. The effect of APC
      on r-TF-mediated platelet activation was concentration-dependent in the range of
      0.5 to 20 micrograms/ml showing an increase in CD-62 expression at lower
      concentrations. In citrated and APC-anticoagulated blood the generation of
      thrombin was studied after IA and EA. At 10 and 20 micrograms/ml APC effectively
      prevented blood clotting which rapidly occurred especially after EA. The amount
      of thrombin generated via the extrinsic pathway was reduced by APC whereas after
      IA F1+2 levels measured in the presence of APC were still strongly increased.
      These results indicate that small amounts of thrombin generated by r-TF are
      sufficient to activate platelets as well as blood coagulation. APC exerts strong
      concentration-dependent anticoagulant actions and effectively prevents activation
      of platelets.

PMID- 9259111
TI  - Expression of rat thrombin receptor and mutants in the baculovirus-infected
      insect cell system.
AB  - The rat thrombin receptor (TR-1) has been expressed in Sf9 cells. Two mutant
      receptors, one lacking a thrombin cleavage site (RTRM), and the other containing
      only the extracellular domain of the receptor (ECD), have been expressed.
      Antibodies to the thrombin receptor activating peptide (TRAP) and to the
      fibrinogen-binding exosite have been prepared. On Western blots these antibodies
      bound to TR-1 bands of 65-70 kDa and 44 kDa, similar bands for RTRM, and a
      doublet of about 10 and 12 kDa for ECD. The free cytosolic Ca++ concentration,
      measured by Fura-2, increased after thrombin or TRAP stimulation in the cells
      expressing TR-1. The RTRM cells did not respond to thrombin and had an attenuated
      response to TRAP. The ECD protein was found in the medium; it was not
      glycosylated. Both the mutants and the antibodies should be useful for studies of
      TR-1 structure and function.

PMID- 9259112
TI  - Effectiveness of low-dose ASA in prevention of secondary ischemic stroke, the ASA
      Study Group in Taiwan.
AB  - This randomized double-blind controlled study was carried out to investigate the
      effect of 100 mg acetylsalicylic acid (ASA) per day on the secondary prevention
      of ischemic stroke. Patients who suffered a first ischemic stroke from 13
      participating hospitals were enrolled. They were independent or only partially
      dependent in activities of daily living and all had received brain CT for
      diagnosis. Eligible patients were randomly allocated to the 100 mg ASA or the
      nicametate citrate (a vasodilator) groups, and trial medications were started
      within three to six weeks after the onset of stroke. The primary end point was
      cerebral reinfarction, and intracranial hemorrhage was classified as an adverse
      event. Four hundred and sixty-six patients participated in this study; and 222
      cases (136 males and 86 females) were allocated to the ASA group while 244 cases
      (150 males and 94 females) were assigned to the nicametate group. No significant
      difference in baseline characteristics between the two groups was observed.
      Cerebral reinfarction developed 6.3% (14/222) in the ASA group and 11.9% (29/244)
      in the nicametate group. According to the Cox's proportional hazards model, the
      estimated risk ratio (ASA group vs. nicametate group) was 0.538, with a 95%
      confidence interval of 0.284-1.019. The result was of borderline statistical
      significance. The risk for cerebral reinfarction was reduced by almost 50% among
      those who took 100 mg ASA versus those who took nicametate.

PMID- 9259113
TI  - Vascular dementia Italian sulodexide study (VA.D.I.S.S.). Clinical and biological
      results.
AB  - In order to evaluate the biological effects on some haemostasis factors of
      antithrombotic-hemorheological treatments on patients with vascular dementia, a
      multicenter, randomized, double-blind, double-dummy, study comparing sulodexide
      (Sdx, 50 mg bid orally for 6 months) and pentoxifylline (Ptx, 400 mg tid orally
      for six months) was carried out. Eighty-six patients, 46 in Sdx group, 40 in Ptx
      group, fulfilling the NINDS-AIREN criteria for probable vascular dementia were
      evaluated. Plasma fibrinogen levels showed a significant reduction in both
      groups, in patients with high basal levels (> or = 350 mg/dl), the reduction
      being earlier in Sdx group (2nd month of therapy) than in Ptx group (4th month of
      therapy). In Sdx group a significant reduction in factor VII-Ag (baseline 102.8
      U/dl; 6th month 90.1 U/dl) was also observed. Both drugs induced a slight
      reduction in activated factor VII levels as well. A parallel improvement of
      G.B.S. Rating Scale for dementia scores was observed in Sdx group. These results
      seem to indicate that sulodexide treatment can have positive effects in vascular
      dementia.

PMID- 9259115
TI  - Further investigations of lupus anticoagulant interference in a functional assay
      for tissue factor pathway inhibitor.

PMID- 9259114
TI  - Characterization of the gene encoding mouse platelet glycoprotien Ib beta.
AB  - Platelet glycoprotein (GP) Ib/IX/V complex is a major receptor for von Willebrand
      factor (vWF), which mediates platelet adhesion and aggregation under high shear
      stress conditions. It is composed of GPIb alpha, GPIb beta, GPIX, and GPV. All
      subunits for the human receptor have been cloned and characterized. However, the
      function of GPIb beta is still elusive. To obtain further information of GPIb
      beta, we have determined the genomic sequence of mouse GPIb beta (1466 bp). The
      deduced amino acid sequence (206aa) was 88% identical to the human GPIb beta
      protein. All cysteine residues, putative N-linked glycosylation site (Asn41), and
      putative phosphorylation site (Ser166) were conserved. The promoter region
      contained putative GATA and ets binding motif implicated in megakaryocytic
      expression. Mouse GPIb beta also contained a leucine-rich glycoprotein (LRG)
      sequence of 24 amino acids same as human GPIb beta.

PMID- 9259116
TI  - Cancer procoagulant activity studies using synthetic peptidyl substrates.

PMID- 9259117
TI  - Platelet response during prostaglandin E1-therapy in patients with non-insulin
      dependent diabetes mellitus.

PMID- 9259118
TI  - Molecular mechanism for APC resistance in the absence of Arg 506 mutation: factor
      V gene sequencing strategy.

PMID- 9259119
TI  - The structure of ethnic attitudes: the effects of target group, region, gender,
      and national identity.
AB  - The present study was an assessment of attitudes of 410 ethnically Dutch
      adolescents toward three ethnic minority groups living in the Netherlands.
      Stereotypes, symbolic beliefs, affective associations, and the evaluation of
      possible interactions were used to predict the global evaluation of ethnic
      outgroups and accounted for much of the variance in ethnic attitudes. The
      relative importance of the four predictors varied by target group and location.
      Gender differences were found in the structure of attitudes; symbolic beliefs
      played a greater role in the attitudes of boys, whereas emotions played a more
      central role in the attitudes of girls. The evaluation of Dutch identity was
      related to the favorability of ethnic attitudes and also to the underlying
      structure. Respondents with a positive national identity had less favorable
      ethnic attitudes, and emotions were more predictive of their attitudes, whereas
      symbolic beliefs were most predictive among respondents with a less positive
      national identity.

PMID- 9259120
TI  - The performance of hearing-impaired children on handedness and perceptual motor
      tasks.
AB  - The present study was designed to test for differences, if any, in children with
      impaired hearing compared with a control group of children with normal hearing (7
      11-year-olds) in handedness, drawing, categorization, facial recognition, and
      play. Results indicated age differences in the performance of all the tasks. The
      children with hearing loss had more left-hand responses than the normal children
      did. For drawings, those whose hearing was impaired used more space and color.
      Both groups performed similarly on tasks of categorization and facial
      recognition. For play, children with hearing loss were more clumsy and accident
      prone than children in the control group. The results suggest that children with
      impaired hearing differ from those with normal hearing in tasks that are
      influenced by language processes and motor ability.

PMID- 9259121
TI  - The structure of empathy during middle childhood and its relationship to
      prosocial behavior.
AB  - This study was an investigation of the structure and development of dispositional
      empathy during middle childhood and its relationship to altruism. A sample of 478
      students from 2nd, 4th, and 6th grades completed an altruism questionnaire and a
      social desirability scale, both created for this study, and the Interpersonal
      Reactivity Index (Davis, 1980), adapted for this study. Teachers also rated the
      students on prosocial behaviors, such as sharing. In addition, as an experimental
      part of the study, the children could make monetary donations and volunteer time
      to raise funds. Results of a confirmatory factor analysis on the Interpersonal
      Reactivity Index supported Davis's (1980) findings that empathy comprises four
      components: perspective taking, fantasy, empathic concern, and personal distress.
      Factor intercorrelations, however, were not the same as those reported by Davis.
      MANOVAs were used to examine gender and age effects on empathy. Girls were more
      empathic in general than boys, and older children showed more empathic concern
      than younger children. Only empathic concern and perspective taking were
      significant predictors of prosocial behavior.

PMID- 9259122
TI  - Anatomy and histochemistry of spread-wing posture in birds. 2. Gliding flight in
      the California gull, Larus californicus: a paradox of fast fibers and posture.
AB  - Gliding flight is a postural activity which requires the wings to be held in a
      horizontal position to support the weight of the body. Postural behaviors
      typically utilize isometric contractions in which no change in length takes
      place. Due to longer actin-myosin interactions, slow contracting muscle fibers
      represent an economical means for this type of contraction. In specialized
      soaring birds, such as vultures and pelicans, a deep layer of the pectoralis
      muscle, composed entirely of slow fibers, is believed to perform this function.
      Muscles involved in gliding posture were examined in California gulls (Larus
      californicus) and tested for the presence of slow fibers using myosin ATPase
      histochemistry and antibodies. Surprisingly small numbers of slow fibers were
      found in the M. extensor metacarpi radialis, M. coracobrachialis cranialis, and
      M. coracobrachialis caudalis, which function in wrist extension, wing
      protraction, and body support, respectively. The low number of slow fibers in
      these muscles and the absence of slow fibers in muscles associated with wing
      extension and primary body support suggest that gulls do not require slow fibers
      for their postural behaviors. Gulls also lack the deep belly to the pectoralis
      found in other gliding birds. Since bird muscle is highly oxidative, we
      hypothesize that fast muscle fibers may function to maintain wing position during
      gliding flight in California gulls.

PMID- 9259124
TI  - Maturation of tympanic membrane layers and collagen in the embryonic and post
      hatch chick (Gallus domesticus).
AB  - The surface area of the chick (Gallus domesticus) tympanic membrane (TM)
      increases by as much as 400% from hatching to 70 days of age (Cohen et al. [1992]
      J. Morphol. 212:187-193). The present study is concerned with the processes that
      contribute to this remarkable size increase. Middle-ear specimens were harvested
      in embryos aged between E10 and E18, and in post-hatch animals between days P1
      and P57. Specimens were embedded in paraffin, cut in serial sections, stained for
      collagen fibers, and examined with light microscopy. Four locations were examined
      in each specimen: the anterior and posterior perimeter of the TM, the TM, over
      the extra-stapedius, and the TM at the tip of the extra-columella. The thickness
      of the epithelial, respiratory, and lamina propria layers was measured at each
      location. The radial collagen fibers in the lamina propria were also counted at
      each location, and fiber density per square micrometer was determined at each
      age. Thickness of the epithelial and respiratory layers remains relatively
      constant throughout development in all areas of the TM, whereas the lamina
      propria at the extra-columella and extra-stapedius continues to thicken with
      increasing age. Collagen density also increases during development, and this is
      attributed to an increase in fiber number and a reduction in the space between
      fibers. The results suggest that collagen may be synthesized first in the central
      regions of the TM and then later in more peripheral areas of the TM.

PMID- 9259123
TI  - Axial orthogonal fiber reinforcement in the penis of the nine-banded armadillo
      (Dasypus novemcinctus).
AB  - Examination of histological sections from flaccid and artificially erected nine
      banded armadillo (Dasypus novemcinctus) penises confirms that the mammalian
      corpus cavernosum is the first known biological hydrostat reinforced by collagen
      fibers arranged at 0 degree and 90 degrees to its long axis. The morphology of
      this axial orthogonal fiber array affects the mechanical behavior of mammalian
      penises during erection and copulation. Specifically, the axial orthogonal array
      gives the erect penis a reproducible shape, maximum size and resistance to
      tensile, compressive, and bending forces. These features are more appropriate for
      the mechanical regime associated with copulation than those found in structures
      reinforced by crossed-helical fibers, although the axial orthogonal array also
      gives the corpus cavernosum a tendency to fail by kinking. Crimped collagen
      fibers in the flaccid array as well as three-dimensional folding of the wall in
      the flaccid corpus cavernosum allow the structure to expand during erection.

PMID- 9259125
TI  - Osteology and skeletal development of Discoglossus sardus (Anura:Discoglossidae).
AB  - Although frogs in the archaeobatrachian family Discoglossidae are reasonably well
      known, descriptions of their larval skeletons and osteogenesis are almost
      nonexistent. Skeletogenesis, chondrocranial development, and the adult skeleton
      of Discoglossus sardus are described on the basis of cleared and stained, dry,
      and radiographed specimens. In D. sardus, the first elements to ossify are the
      parasphenoid, frontoparietals, exoccipitals, neural arches, ischium, long bones,
      and dermal elements of the pectoral girdle (Gosner Stage 36). Major
      reconstruction of the chondrocranium begins at the onset of metamorphosis (Stage
      41), contemporaneous with the ossification of the premaxillae, maxillae, vomers,
      and septomaxillae. Several cranial (e.g, pterygoid, mentomeckelian, sphenethmoid)
      and postcranial (e.g., carpals, hyoid) elements do not commence ossification
      until metamorphosis (Stage 46). Discoglossids are characterized by the presence
      of a facial foramen in the lateral wall of the chondrocranium, a rod-like
      epipubis developing from two primordia, and the lack of a neopalatine bone. Adult
      male Discoglossus possess an enlarged, crested metacarpal II and a broad
      prepollical element. This detailed description serves as a model to compare the
      development of other discoglossid frogs and provides detailed descriptions of
      several enigmatic structures.

PMID- 9259126
TI  - Elastic structures in the vocalization apparatus of the Tungara frog Physalaemus
      pustulosus (Leptodactylidae).
AB  - Histological analysis of the vocal sac and body wall in the leptodactylid frog
      Physalaemus pustulosus suggests that both muscle and elastic fibers are important
      in call production. Abdominal musculature as well as abdominal bands of elastin
      (the lineae masculinae) provide the energy required for exhalation and sound
      production. Air flowing through the larynx inflates a highly extensible vocal sac
      lined with muscle and a network of elastic fibers. Inherent elasticity together
      with muscular activity of the vocal sac likely increase the speed and possibly
      decrease the energetic costs of lung reinflation following vocalization. The
      mechanics of call production in P. pustulosus thus involve not only laryngeal
      activation but also elastic transfer of air between the supralaryngeal vocal sac
      and abdominal respiratory structures.

PMID- 9259127
TI  - [Epidemiological evaluation of mycobacteria isolates in one city hospital:
      reports from the hospital microbiology laboratory].
AB  - The frequency of mycobacteria isolated from patient's specimens at Showa
      University Fujigaoka Hospital was investigated. By fitting a polynominal curve
      (degree = 3) of the annual frequency of culture-positive Mycobacterium
      tuberculosis (1977 through 1995), it was noted that the frequency had not changed
      since 1977. The patients in the 40s or older and 60s or older comprised 74 and
      38%, respectively. Of 104 patients diagnosed as tuberculosis (between 1993 and
      1995), 43 (41%) were compromised hosts with the following underlying diseases:
      kidney disease; diabetes mellitus; malignant tumor; respiratory disease; Behcet's
      disease; ophthalmosarcoidosis; multiple arthritis; Hashimoto's disease. This
      suggested that these compromised hosts are at high risk of onset and relapse of
      tuberculosis, and occasionally the doctor's or patient's delay was seen during
      the diagnostic process. By fitting a polynominal curve (degree = 3) of the annual
      frequency of culture-positive atypical mycobacteria (1977 through 1995), it was
      noted that the frequency had increased since 1981. The patients in the 40s or
      older and 60s or older comprised 88 and 60%, respectively. Between 1982 and 1994,
      we encountered 46 cases of atypical mycobacteriosis of the lung: 37 M. avium
      complex (MAX) diseases; 7 M. kansasii diseases; one M. chelonae disease; one
      unidentified disease involving Runyon Group II mycobacterium. Eight involved
      patients with bronchiectasia (5 cases), diabetes mellitus (2 cases), or leukaemia
      (one case). Haemophilus influenzae, Pseudomonas aeruginosa, and Moraxella
      catarrhalis at more than 10(7) CFU per ml of sputum were isolated from 6 patients
      diagnosed with MAC or M. kansasii lung diseases, suggesting the possibility of
      mixed infections. M. tuberculosis and atypical mycobacterium (15 cases), and two
      different atypical mycobacteria (16 cases) were isolated from the same or
      different specimens of the same patients at the same or different times. However,
      the pathogenicity of these mycobacteria remained unknown, because atypical
      mycobacteria are non-pathogenic in many cases. The above findings suggested that
      the environment fit for the mycobacteria growth in human body has gradually been
      formed associating with aging, lung-lesion, and decline of immune capacity.

PMID- 9259128
TI  - [A case of Mycobacterium intracellulare infection associated with sinobronchial
      syndrome].
AB  - The patient was 71-year-old male with a history of sinobronchial syndrome since 8
      years ago. He has been suffering from cough, sputum and upper abdominal
      discomfort since January 1994. He was diagnosed as an early gastric cancer by
      endoscopy, and his chest X-ray film showed an infiltrative shadow in the right
      upper lung field. A smear of the sputum specimen was positive for acid fast
      bacilli, which were later identified as Mycobacterium intracellulare. In this
      case, before the Mycobacterium intracellulare infection, it was confirmed that
      his mucociliary transport was severely impaired by using aerosol inhalation cine
      scintigraphy. This case suggests that an impairment of the local defence
      mechanisms may play an important role in the pathogenesis of Mycobacterium
      intracellulare infection.

PMID- 9259129
TI  - [Anti-Mycobacterium avium complex activities of KRM-1648, clarithromycin and
      levofloxacin in 7HSF medium at peak or average blood concentrations after their
      oral administration of clinical dosages].
AB  - We evaluated the anti-Mycobacterium avium complex (MAC) activities of KRM-1648
      (KRM), clarithromycin (CAM) and levofloxacin (LVFX) in 7HSF medium at
      concentrations in human blood after their oral administration of clinical
      dosages. MAC organisms were inoculated into tubes containing the medium with or
      without the addition of test drugs at either 1/10 Cmax, Cmax or C0-8h (average
      concentrations during the first 8 h) in the blood. KRM at Cmax or C0-8h showed
      strong bactericidal activity against MAC, CAM showed weak or moderate degree of
      bactericidal activity at Cmax and C0-8h, while LVFX added at Cmax or C0-8h showed
      only a weak bacteriostatic effect against M. avium, but did not show any effect
      against M. intracellulare.

PMID- 9259130
TI  - [Prediction of postoperative pulmonary hemodynamics for the second lobectomy
      after the contralateral lobectomy].
AB  - We presented 7 cases who were performed the second lobectomy for the second lung
      cancer after the first successful lobectomy on the contralateral lung (3 cases
      for right upper lobectomy + left lower lobectomy and 4 cases for right upper
      lobectomy + left lower lobectomy). In 6 patients, the predicted postoperative
      FEV1 estimated by multiplying the preoperative FEV1 by the fraction of perfusion
      to the contralateral lung was less than 800 ml/m2BSA, which is our first cut-off
      for identifying lung resection candidates. Unilateral pulmonary arterial
      occlusion test (UPAO) revealed that total pulmonary vascular resistance (TPVRI)
      in 3 of those 6 patients was lower than 700 dyne.sec.cm-5/m2BSA, our second cut
      off for lung resection. More precise postlobectomy pulmonary hemodynamics in
      another 3 of those 6 patients were then estimated by adapting selective pulmonary
      occlusion test (SPAO). Since TPVRI during SPAO was lower than the cut-off value,
      it was suggested that second lobectomy would be feasible with low incidence of
      post operative cardiopulmonary complication. There was no serious complications
      in all 7 cases during their postoperative course. We believe that more precise
      prediction of postoperative pulmonary hemodynamics by adapting UPAO and SPAO
      could be one of the tools to minimumize postoperative cardiopulmonary
      complications in those patients needed second lobectomy for the second lung
      cancer after the first successful lobectomy on the contralateral lung even though
      their impaired lung fung function.

PMID- 9259131
TI  - [Diversion of the inferior vena cava into the left atrium after repair of atrial
      septal defect with partial anomalous pulmonary venous drainage].
AB  - An 11-year-old female had operative repair of atrial septal defect associated
      with partial anomalous pulmonary venous drainage by direct suture at 6-year-old.
      Postoperatively, cyanosis and nodal bradycardia were noted by physical exercise.
      During 5 years thereafter, the symptoms were gradually aggravated accompanying.
      Cardiac catheterization revealed diversion of the inferior vena cava into the
      left atrium. Oxygen sampling showed right to left shunt of 22% at the atrial
      level. At reoperation, orifice of the inferior vena cava into the right atrium
      became narrow 5 mm in diameter. After enlargement of the orifice, the atrial
      septum was created with a Gore-Tex patch to redirect the inferior vena cava to
      the right atrium. Post operative course was uneventful with disappearance of the
      cyanosis. The patient is up and well now 9 years after reoperation.

PMID- 9259133
TI  - [New method for closure of median sternotomy: usefulness of barbed staple].
AB  - In this report, 15 cases using straight staple (group A) and 35 cases using
      barbed staple (group B) were compared for the purpose of investigating efficacy
      for median sternal closure. The staples were placed by a Stapilizer powered
      metaphyseal staple system following partial transsternal fixation with two wires.
      As a means of assessing the status of back out, which is a major cause of poor
      fixation, the back out rate (BOR) was measured on lateral sternal radiographies.
      The average BOR was found to be 33.8% in group A and 21.2% in group B (p <
      0.001). Barbed staples seemed to be more useful for sternal fixation than
      straight staples. This method of applying barbed staples had the advantages of
      speed, ease of insertion and noninvasion of the retrosternal region. It should be
      recommended in cases with severe adhesion of the retrosternal region after
      coronary operation.

PMID- 9259132
TI  - [Mediastinal lymph-node carcinoma with no apparent primary lesion].
AB  - To determine the clinical characteristics of cases of hilar or mediastinal lymph
      node cancer in which the primary lesion was not found; reports of 36 such cases
      were identified. The patients in those cases comprised 29 men and 7 women, whose
      average age was 58.4 years. The malignancies were found in hilar lymph nodes in
      15 patients, mediastinal lymph nodes in 16, and both hilar and mediastinal lymph
      nodes in 4; 14 were adenocarcinomas, 4 were squamous-cell carcinomas, and 4 were
      small-cell carcinomas. The average length of cancer-free survival after surgery
      was 28.9 months, and the maximum was 9 years. After the affected hilar and
      mediastinal lymph nodes had been resected the clinical appearance of these
      patients was the same as if the primary tumor had been removed. We therefore
      believe that many patients given a diagnosis of cancer with metastases to hilar
      or mediastinaly lymph nodes and in whom the primary tumor cannot be located in
      fact have primary cancer of the lymph nodes, and that this condition should be
      called "primary mediastinal lymph-node carcinoma".

PMID- 9259134
TI  - [Development of a blood cardioplegia delivery system for children].
AB  - We have developed a blood cardioplegia delivery system for children. Essential
      points of a delivery system in pediatric cardiac surgery are (1) a small amount
      of priming volume of a delivery system, and (2) slow, steady infusion of a
      cardioplegic solution. We changed a heat exchanger to a smaller one for reduction
      of priming volume, and changed a roller pump tube to a smaller one for slow,
      steady infusion. Thus, priming volume of a delivery system has reduced from 180
      to 100 ml, and we can infuse a cardioplegic solution at a steady rate less than
      10 ml/min. Our clinical experience with this system suggests that this blood
      cardioplegia delivery system is useful for pediatric cardiac surgery.

PMID- 9259136
TI  - [Transverse submammary skin incision for congenital cardiac surgery].
AB  - Submammary skin incision has been accepted as cosmetic approach for open heart
      surgery. During November 1990 to February 1995, 39 ASD patients under 15 years
      old were operated with either median or submammary skin incision in Okayama
      University Medical School. For these patients, retrospective study was carried
      out to determine whether submammary skin incision made surgical procedure complex
      and whether patients were satisfied with the scar by submammary skin incision.
      There were 14 submammary skin incision (Group S) and 25 median skin incision
      (Group M). There was no significant difference in patients profile between the
      two groups except for sex. Operative time, cardiopulmonary bypass time and aortic
      cross clamp time had no significant difference between the two groups.
      Postoperative ICU stay and hospital stay also did not differed between the two
      groups. Questionnaires for evaluation of the subjective operation scar was sent
      with 32 answers (82%). There was no significant difference on questionnaire
      findings. However for the patients without hypertrophic scar, more patients in
      Group S were significantly satisfied with their scars. Submammary skin incision
      was safe and easy. It could be alternative of median skin incision. If
      hypertrophic scar formation could be prevented, more patients would be satisfied
      with submammary skin incision than median skin incision.

PMID- 9259135
TI  - [The efficacy of HFJV (high frequency jet ventilation) for ARDS (adult
      respiratory distress syndrome) following total arch replacement].
AB  - A 40-year-old man was admitted to the hospital with shock due to acute aortic
      dissection (type A of Stanford classification). The emergent total arch
      replacement was performed with the retrograde cerebral perfusion uneventfully. At
      the 3rd day after the operation, bilateral infiltrates were recognized on the
      frontal chest radiograph. The oxygenation was gradually decreased to less than
      200 mmHg of PaO2/FiO2 in proportion with the growth of infiltrates and increase
      of LDH in blood. Steroid therapy was not effective. So then HFJV was introduced
      to improvement of hypoxygenation at the 16th day after the operation. HFJV made
      PaO2/FiO2 improve immediately to more than 300 mmHg and the inspiratrory pressure
      decrease to less than 30 mmHg. Bilateral infiltrates were diminished by HFJV. LDH
      in blood decreased apparently. HFJV had been used together during 15 days. The
      respirator was weaned at the 46th day after the operation. In this clinical
      course, the change of PaO2/FiO2 had the negative correlation with that of LDH in
      blood.

PMID- 9259138
TI  - [Heart and lung surgery '86-'96].
AB  - During a period between April 1, 1986 and December 31, 1996, a total of 3,190
      cardiothoracic operations were performed in our department. The overall mortality
      was 4.1%. The prerequisite for successful accomplishment of clinical research was
      discussed in detail.

PMID- 9259139
TI  - [A case report on prosthetic valve dysfunction of the Carpentier-Edwards
      pericardial bioprosthesis in the tricuspid position associated with remarkable
      hypoproteinemia].
AB  - A 66-year-old woman underwent a second tricuspid valve replacement because of a
      malfunction of the Carpentier-Edwards pericardial bioprosthesis (CEP) in the
      tricuspid position 3.5 years after her first mitral and tricuspid valve
      replacement. The major symptom was lower leg edema and a serum albumin level
      ranging between 1.5 g/dl and 2.0 g/dl. The remarkable hypoproteinemia might have
      resulted from impaired albumin synthesis due to liver dysfunction, hemodilution,
      protein losing gastroenteropathy, and changes in albumin distribution due to
      edema. Although the explanted CEP showed neither dehiscence nor calcification of
      the leaflet, fibrous pannus mainly on the ventricular side restricted the
      mobility of the corresponding leaflet. Patients receiving a CEP in the tricuspid
      position should receive careful follow-up.

PMID- 9259137
TI  - [A case report: successful treatment of acute type B aortic dissection with renal
      and leg ischemia].
AB  - A 56-year-old patient of acute type B aortic dissection with renal and leg
      ischemia successfully underwent emergency replacement of the descending thoracic
      aorta. Prior to this operation, we reperfused the ischemic legs in a controlled
      manner using a cardiopulmonary bypass circuit. This controlled limb reperfusion
      method could reduce reperfusion injury. Postoperatively, the patient also
      suffered from renovascular hypertension due to stenosis of the right renal
      artery. Renal stent angioplasty, performed 10 days after the operation,
      stabilized his blood pressure. Controlled limb reperfusion and renal stent
      angioplasty may be useful for managing branch complications associated with
      aortic dissection.

PMID- 9259140
TI  - [A case of coronary artery bypass grafting without cardiopulmonary bypass in a
      patient with left ventricular dysfunction].
AB  - A 54-year-old man who had severe deterioration of left ventricular function
      (cardiac index ; 1.6 l/min/m2, left ventricular ejection fraction ; 26%) due to
      two myocardial infarcts underwent bypass of the left anterior descending artery
      using the left internal thoracic artery under IABP assist without extracorporeal
      circuration or cardiac arrest. Two hours postoperatively, he was extubated.
      Subsequent clinical course was uneventful with a satisfactory outcome. These
      findings suggest that coronary artery bypass without extracorporeal circulation
      or cardiac arrest is a safe and effective procedure in patients with left
      ventricular dysfunction.

PMID- 9259142
TI  - [Emergent coronary artery bypass grafting in a patient with mirror-image
      dextrocardia].
AB  - A 49 year-old-man with known situs inversus totalis was admitted to our hospital
      with a history of angina pectoris of 4 months duration. Coronary arteriography
      revealed that the left main trunk had a 90% stenosis. After the arteriography,
      the patient's hemodynamics was deteriorated, and he required a support of
      intraaortic balloon pumping. He underwent emergent coronary artery bypass
      grafting with saphenous veins the following day, and recovered uneventfully.
      Technical problems in this patient from a surgical viewpoint were discussed. As
      far as we know, this is the first case of coronary bypass grafting on a patient
      with mirror-image dextrocardia and a stenosis of the left main trunk.

PMID- 9259141
TI  - [Severe acute cardiac failure caused by the combination of the aortic stenosis
      and sudden onset of the mitral chordae rupture].
AB  - The patient, who had an aortic stenosis, suddenly complicated with severe acute
      cardiac failure. The rupture of the mitral chordae tendineae was detected by the
      echocardiogram. Double replacements (aortic and mitral) were done immediately
      after the onset of chordae rupture. This condition, combination of aortic
      stenosis and sudden onset of chordae rupture, always results in severe heart
      failure which is explained by the combination of pressure and volume loading.
      Finally the emergent operation is believed to be an only solution for this
      situation.

PMID- 9259143
TI  - [Mitral valve prolapse associated with severe pulmonary hypertension: a case
      report].
AB  - Severe (110/50 mmHg) pulmonary hypertension (PH) secondary to mitral valve
      prolapse is rare. We reported herein severe PH secondary to mitral valve prolapse
      in a 65-year-old female. The patient underwent mitral valve replacement and
      tricuspid annuloplasty. The pulmonary artery pressure after the operation
      decreased to 69/20 mmHg. Prostagrandin E1 was effective for residual PH compared
      with nicardipine hydrochloride.

PMID- 9259144
TI  - [A case of mobile left atrial thrombus without mitral valve disease].
AB  - A 70-year-old woman who had a left atrial thrombus without mitral valve disease
      was reported. On admission her electrocardiogram showed atrial fibrillation, but
      there was no cardiac murmur. Transthoracic echocardiogram revealed a dilated left
      atrium and an intact mitral valve, but did not detect any thrombus.
      Transesophageal echocardiogram, however, demonstrated the thrombus attaching to
      the left atrial appendage. Removal of the thrombus and maze procedure were
      performed at the same time. Although a pacemaker (DDDR mode) was required
      postoperatively, she spends uneventful daily life at two years after the surgery.

PMID- 9259145
TI  - [Re-expansion pulmonary edema after emergency thoracotomy for spontaneous
      hemopneumothorax: a case report].
AB  - A 44-year-old man was admitted to out hospital complaining of chest pain and
      increasing dyspnea. Chest X-ray on admission revealed a collapsed lung and an air
      fluid line in the left hemothorax. Following blood transfusion because of 2,000
      ml hemorrhagic pleural fluid, emergent surgery was carried out. At operation, a
      bleeding artery originating from the apex of the thoracic cavity and a bulla on
      the upper lobe were noticed. After extubation of endotracheal tube, he offered
      severe dyspnea with hypoxia. The chest X-ray showed figure of pulmonary edema in
      the left lower lobe. Patient was managed by oxygen, steroid, and urinastatin. On
      the 3rd operative day, pulmonary edema was disappeared. It should be kept in the
      mind that the re-expansion pulmonary edema occurred in patients with spontaneous
      hemopneumothorax of less than 3 days of duration.

PMID- 9259146
TI  - [Malignant fibrous histiocytoma of the chest wall: a case report].
AB  - A 74-year-old man was admitted to our hospital with a cough. His chest X-ray
      film, chest CT scan and MRI showed a tumor of the chest wall. Histology of a
      percutaneous needle biopsy revealed malignant fibrous histiocytoma (MFH). The
      tumor enlarged rapidly, and the patient underwent resection including the 6th,
      7th and 8th ribs and partial resection of the right diaphragm and the right
      middle and lower lung lobes. Multiple pulmonary metastases were found 40 days
      after the operation, and the patient died of respiratory failure 4 months after
      surgery. Although MFH is one of the most common soft tissue sarcomas, lesions
      arising from the chest wall are uncommon. We stress the need for early diagnosis
      and aggressive surgical resection in the treatment of MFH arising from the chest
      wall.

PMID- 9259147
TI  - [A case of mediastinal cystic lymphangioma with bloody fluid].
AB  - A 53-year-old woman was admitted to our hospital for chest abnormal shadow. Chest
      CT showed a mediastinal cyst. Tumor resection was performed and the cyst turned
      out to be a cystic lymphangioma with bloody fluid. There were many lymphocytes in
      the fluid. She lives well without recurrence.

PMID- 9259148
TI  - [A case of the old injured vena cava superior found during the operation of lung
      cancer].
AB  - We operated a 78-year-old male with lung cancer and unstable angina pectoris.
      During the operation of right upper lobe, a mass, with size of 2 cm in diameter
      was detected on the right postero-lateral side of the superior vena cava, and was
      resected. Postoperative pathological examination suggested that the mass resulted
      from an injury made by a Swan-Ganz catheter used before operation. Thus, as
      insertion of a Swan-Ganz catheter through the right subclavian vein may involve
      risk, so we concluded that the right internal jugular vein or femoral vein may be
      preferable as a route of first choice for insertion.

PMID- 9259150
TI  - Moyamoya disease in Yugoslavia: angiographic study.
AB  - The angiographic findings in 31 Yugoslav moyamoya patients, 16 males and 15
      females, including four children, were studied by conventional or digital
      subtraction angiography. The angiographic findings were reviewed for
      stenoocclusive lesions, form of the main cerebral arteries, transdural
      anastomoses, and basal vascular networks. There were 27 patients with bilaterally
      symmetrical or asymmetrical lesions and four with unilateral lesions. In two of
      these latter four patients, follow-up studies showed progression of the disease
      to the opposite side. Of 58 sides investigated, stenoocclusive lesions were
      localized above the origin of the anterior choroidal artery in 33 internal
      carotid arteries. Occlusions of the anterior and middle cerebral arteries were
      noted more frequently than stenoses: 89 vs. 27. The majority of the nests of
      abnormally dilated vessels (73 of 102) were localized in the ethmoidal region and
      basal ganglia. Analysis of distribution of the transdural collateral pathways to
      the brain discovered predominant participation of the middle meningeal and
      occipital arteries (43 of 55). Moyamoya disease in Yugoslavia predominantly
      affects the adult population, males and females equally, with the slowly
      progressive course typical for adults, and is mainly confined to the carotid fork
      and rarely extends to the posterior circulation.

PMID- 9259149
TI  - Preoperative detection of the composition of atherosclerotic plaque in the
      carotid artery using ultrasonography and magnetic resonance imaging.
AB  - Preoperative identification of the components of atherosclerotic plaque was
      attempted using ultrasonography in five patients and magnetic resonance (MR)
      imaging in three patients before carotid endarterectomy. The correlation between
      surgical and histological findings, and preoperative ultrasonography and MR
      imaging was evaluated. Plaque consisting predominantly of calcification appeared
      as bright echo on ultrasonography and was tough. Plaque consisting predominantly
      of hemorrhage was echolucent, appeared as low intensity on T2-weighted MR images
      and was fragile. Such preoperative assessment of plaque composition using
      ultrasonography and MR imaging is useful for manipulation of atherosclerotic
      plaque during carotid endarterectomy.

PMID- 9259151
TI  - Short-latency somatosensory evoked potentials in patients with brain stem tumor:
      study of N20 and N18 potentials.
AB  - Short-latency somatosensory evoked potentials (SSEPs) elicited by median nerve
      stimulation were studied in 17 patients with brain stem tumor. A total of 35 SSEP
      records were obtained and classified into five groups: 13 in Group I, central
      conduction time (CCT) < 7.56 msec (within the normal limits); eight in Group II,
      CCT > or = 7.56 msec; nine in Group III, N20 potential was abolished; four in
      Group IV, N20 and N18 potentials were abolished; and one in Group V, N20, N18,
      and P14 potentials were abolished. These SSEP groups were correlated with the
      size and location of the brain stem tumor on magnetic resonance images. N20
      potentials were unchanged in latency in patients with small localized gadolinium
      (Gd)-enhanced lesions. In contrast, the N20 potentials were abolished in patients
      with tumors extending to the dorsal pons and the upper medulla oblongata. The
      extent of nonenhanced low-intensity lesion did not correlate with the changes of
      the N20 potentials. The degree of the impairment of the N20 potentials reflected
      the severity of the clinical symptoms. The N20 potential can evaluate brain stem
      dysfunction caused by brain stem tumor. The N18 potentials were abolished in four
      patients, in whom the tumor extension (one Gd-enhanced lesion, three low
      intensity lesions) involved not only the pons but also the medulla oblongata.
      Therefore, the N18 potentials are probably generated from the medulla oblongata.

PMID- 9259152
TI  - Acute subdural hematoma without subarachnoid hemorrhage due to ruptured
      intracranial aneurysm--case report.
AB  - A 54-year-old female presented with acute subdural hematoma secondary to rupture
      of an intracranial aneurysm. She was admitted with acute onset of severe
      headache, nausea, and vomiting. There was no past history of head trauma.
      Computed tomography demonstrated a left subdural hematoma with extension along
      the tentorium in the absence of subarachnoid or intraparenchymal hemorrhage.
      Angiography revealed an aneurysm of the internal carotid-posterior communicating
      artery which was oriented posterolaterally. Uneventful clipping was performed and
      the patient was discharged from hospital without neurological deficits. The
      possibility of aneurysmal subdural hematoma should be considered in the absence
      of trauma.

PMID- 9259153
TI  - Cerebellar infarction with hydrocephalus caused by spontaneous extracranial
      vertebral artery dissection--case report.
AB  - A 38-year-old male suffered sudden onset of rotational vertigo without headache.
      Consciousness disturbance developed on the 3rd day after the onset. Computed
      tomography showed cerebellar infarction with obstructive hydrocephalus. External
      ventricular drainage was performed. Angiography showed bilateral extracranial
      vertebral artery dissection. Antiplatelet therapy was given. Repeat angiography
      showed improvement of the dissection. His neurological deficits completely
      resolved. Vertebral artery dissections may cause both lateral medullary or
      cerebellar infarction and hydrocephalus due to the cerebellar infarction
      manifesting as various symptoms so careful evaluation and treatment are required.

PMID- 9259154
TI  - Childhood ischemic stroke caused by fibromuscular dysplasia of the intracranial
      artery--case report.
AB  - An 8-year-old girl presented with fibromuscular dysplasia of the intracranial
      vessels manifesting as ischemic stroke. Neuroimaging showed infarction of the
      right putamen and ipsilateral frontal white matter. Angiography revealed "string
      of beads" sign involving the terminal portion of the right internal carotid
      artery and the horizontal segment of the ipsilateral middle cerebral artery. She
      was treated conservatively. Magnetic resonance angiography at 2 months post ictus
      showed similar findings in the middle cerebral artery but improvement of the
      stenosis of the internal carotid artery. Her neurological deficits had almost
      resolved. Fibromuscular dysplasia should be part of the differential diagnosis of
      ischemia in children.

PMID- 9259155
TI  - Carcinomatous change in the cranial metastasis from a metastasizing mixed tumor
      of the salivary gland--case report.
AB  - A 57-year-old female who had had a mixed tumor of the submandibular gland for 30
      years presented with a cranial metastasis in the ipsilateral occipital region.
      Detailed histological examinations of the primary tumor failed to detect any
      carcinomatous component. In contrast, the metastasis contained a carcinomatous
      component. This histological discrepancy was confirmed by assessment of the
      expression of Ki-67 antigen in these tumor specimens and comparison with five
      typical benign mixed tumors. Cranial metastasis of a histologically benign mixed
      tumor is extremely rare, and a carcinomatous change in the metastatic tumor is
      apparently unique.

PMID- 9259156
TI  - Intracerebral Schwannoma--case report.
AB  - A 15-year-old girl presented with a rare intracerebral schwannoma manifesting as
      epileptic seizure. Computed tomography, magnetic resonance imaging, and cerebral
      angiography showed a right parietooccipital lobe tumor. The preoperative
      diagnosis was malignant glioma, but immunohistochemical and ultrastructural
      examinations showed the tumor was indistinguishable from peripheral schwannoma.
      Only 29 cases of schwannomas not related to the cranial nerve have been reported,
      mostly in children and young adults. The origin appears to be ectopic or
      perivascular elements in the brain. Such intracerebral schwannomas can be
      classified according to origins into intra-axial, periventricular, dural
      attachment, and other types.

PMID- 9259157
TI  - Pure amnesia caused by bilateral temporal lobe astrocytoma--case report.
AB  - A 32-year-old male presented with progressive pure amnesia caused by astrocytoma
      invading the bilateral medial temporal lobes. Methionine positron emission
      tomography demonstrated the extent of tumor invasion well. His memory impairment
      was partially improved by treatment for the astrocytoma. Lesion of the bilateral
      hippocampus causes memory impairment, but pure memory loss without other
      associated neurological sign or deterioration of consciousness is rare in a case
      of cerebral neoplasm.

PMID- 9259158
TI  - Adult respiratory distress syndrome in patients with malignant astrocytoma--three
      case reports.
AB  - Three patients treated for intracranial malignant astrocytomas developed adult
      respiratory distress syndrome (ARDS). All three patients had a Karnofaky
      performance status score of at least 80% and similar clinical characteristics.
      All demonstrated hypersensitivity to phenytoin. ARDS occurred in two patients
      during radiotherapy and in one with radiation-induced brain damage following
      initial radiochemotherapy. ARDS occurred shortly after tapering the long-term
      administration of betamethasone. The initial symptoms were dry cough, fever, and
      generalized toxic eruption. Serum lactic acid dehydrogenase (LDH) concentrations
      were increased up to 2500 IU/l. Several days later, the patients suddenly
      complained of dyspnea. All patients fulfilled the diagnostic criteria for ARDS.
      Two patients recovered, but a young woman died. Clinical symptoms such as fever
      of unknown origin, dry cough and skin eruptions, accompanied by abnormally
      increased serum LDH concentrations during or following the tapering of long-term
      administration of corticosteroids, are warning signs of ARDS in patients being
      treated for malignant gliomas.

PMID- 9259159
TI  - Forbidden knowledge and the cloning of a lamb.

PMID- 9259160
TI  - Pulmonary hypertension: newer concepts in diagnosis and management.
AB  - Pulmonary hypertension comprises a family of disorders occurring as a primary
      disease or as a complication of a large number of respiratory and cardiac
      diseases. Pulmonary hypertension is present when pulmonary artery pressure or
      mean pressure exceeds 30 mmHg or 20 mmHg, respectively. Underlying the
      hemodynamic changes that result in pulmonary hypertension, whether from hypoxia,
      acidosis, increased pulmonary blood flow, increased shear stress, or idiopathic
      causes, is a dysfunctional vascular endothelium. In this review, the role of the
      history and physical examination in the initial assessment is emphasized. Newer
      diagnostic modalities, such as subselective pulmonary angiography and ultrafast
      computed tomography scanning, are reviewed. Low-flow oxygen, anticoagulation, and
      calcium-channel blockade are presented as accepted therapeutic modalities.
      Inhaled nitric oxide and prostacyclin infusion are presented as newer therapies
      that may be useful given the limited availability of donor organs for hear-lung
      transplantation. Future therapeutic strategies are likely to develop from
      advances in vascular biology.

PMID- 9259161
TI  - What can we learn from exercise testing beyond the detection of myocardial
      ischemia?
AB  - Noninvasive cardiopulmonary exercise (CPX) testing has proven useful in the
      assessment of heart and lung disease, including cardiac and ventilatory reserves.
      CPX includes the monitoring of respiratory gas exchange, O2 uptake the CO2
      production, together with minute ventilation and its components--tidal volume and
      respiratory rate--together with surveillance of electrocardiography and blood
      pressure during supervised, incremental exercise. Exercise responses in anaerobic
      threshold and/or maximal O2 uptake are used to grade functional capacity
      objectively and to predict cardiac reserve (exercise cardiac output), which
      grades the severity of chronic cardiac or circulatory failure. CPX also serves to
      distinguish primary cardiac from ventilatory-based exertional dyspnea.

PMID- 9259162
TI  - Reverse remodeling in heart failure with intensification of vasodilator therapy.
AB  - BACKGROUND: Heart failure therapy with beta-receptor blockade has been shown to
      effect a partial reversal of left ventricular (LV) remodeling in heart failure.
      HYPOTHESIS: We tested the hypothesis that, in the absence of beta blockade,
      uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy
      over conventional dosages would improve symptoms as well as LV function in
      patients with severe heart failure. METHODS: For patients with nonischemic or
      ischemic cardiomyopathy, intensive high-dose angiotensin-converting enzyme
      inhibitor and nitrate therapy was uptitrated. Echocardiograms were obtained
      semiannually and evaluated in a blinded fashion. Of 99 patients in the study,
      aged 55 +/- 13 years, with heart failure for 5.2 +/- 3.1 years, 74 were men, 69
      were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril
      was 40 +/- 23 mg/day of isosorbide dinitrate it was 153 +/- 127 mg/day. RESULTS:
      Initial New York Heart Association classification improved from 2.8 +/- 0.9 to
      1.7 +/- 0.9 (p < 0.001) in 2.7 years of follow-up. Of the 99 patients, 72 further
      improved their ejection fraction. For the whole group, ejection fraction
      increased from 21 +/- 9% to 30 +/- 13% in 6 months (p < 0.001), with a reduction
      in LV end-diastolic size from 6.6 +/- 0.9 to 6.3 +/- 1.0 cm (p = 0.002), a
      decrease in the severity of mitral regurgitation from mild/moderate to only mild.
      Resting heart rate declined with no change over time in systemic systolic blood
      pressure. Final ejection fraction for nonischemic patients (n = 65) was 36 +/-
      16% versus 23 +/- 9% for the ischemic population. CONCLUSIONS: Uptitration of
      high-dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in
      severe heart failure, further improves both clinical status and LV systolic
      function, and is more effective in nonischemic than in ischemic cardiomyopathy.

PMID- 9259163
TI  - Dofetilide in patients with left ventricular dysfunction and either heart failure
      or acute myocardial infarction: rationale, design, and patient characteristics of
      the DIAMOND studies. Danish Investigations of Arrhythmia and Mortality ON
      Dofetilide.
AB  - BACKGROUND: Attempts to prolong life with antiarrhythmic drugs in patients at
      increased risk of sudden cardiac death have so far been disappointing or
      inconclusive. HYPOTHESIS: The Danish Investigations of Arrhythmia and Mortality
      ON Dofetilide (DIAMOND) encompass two survival studies testing the prophylactic
      use of the selective potassium-channel blocker, dofetilide, in patients at high
      risk of sudden death. METHODS: The first study includes patients admitted to
      hospital with congestive heart failure (CHF), the other includes patients with
      acute myocardial infarction (MI) within the previous 7 days. In both studies
      patients must have left ventricular systolic dysfunction (ejection fraction < or
      = 35%) determined by echocardiography. Each of the two studies are planned to
      enroll 1500 patients. Consecutive hospitalized patients with MI or CHF are
      screened in 37 Danish hospitals. Eligible patients are randomized to receive
      dofetilide or matching placebo. All patients are continuously monitored by
      telemetry for the first 3 days of the study to detect possible arrhythmic events
      and to ensure resuscitation in case of serious arrhythmias. Minimum duration of
      follow-up is 12 months. RESULTS: Between November 1993 and July 1996, a total of
      5812 consecutive patients with CHF and 8688 consecutive patients with MI was
      screened for entry. Of these, 1518 patients were included in the CHF study and
      1510 patients in the MI study. Overall 1-year mortality of randomized patients
      were 28 and 22%, respectively. CONCLUSION: DIAMOND will provide important data on
      the safety and efficacy of dofetilide in high-risk patients with left ventricular
      dysfunction and either CHF or MI, as well as evaluate tolerability in these
      populations.

PMID- 9259164
TI  - Safety and efficacy of angiography-guided stent placement in small native
      coronary arteries of < 3.0 mm in diameter.
AB  - BACKGROUND AND HYPOTHESIS: Increased operator experience, greater insight in
      stent deployment techniques, and improved poststent medication regimen have
      significantly reduced the risk of thrombotic stent closure following stent
      placement in large coronary arteries (> or = 3.0 mm in diameter). Whether equally
      favorable results are afforded by stent placement in small vessels (< 3.0 mm),
      however, remains unclear. Accordingly, the aim of this study was the specific
      examination of the risk of stent placement in small native coronary vessels,
      using stent deployment technique consisting of supplementary dilatations with
      larger balloons or high-pressure inflations, and aggressive aspirin-ticlopidine
      and short-term oral anticoagulation poststent therapy. METHODS: Forty-seven
      balloon-expandable stents (20 Gianturco-Roubin, 21 NIR, 6 Palmaz-Schatz) were
      successfully implanted without intravascular guidance in 45 native coronary
      arteries (mean reference diameter of 2.5 mm) in 44 consecutive patients (31 men,
      13 men), the majority of whom (87%) were stented for the treatment of failed or
      suboptimal balloon angioplasty outcome. RESULTS: Successful stent placement
      reduced the lesion diameter stenosis from 91 +/- 9% to 3 +/- 7% (p = 0.0001).
      There were no early stent thrombosis or major cardiovascular events prior to
      hospital discharge. During a 12-month follow-up period, most patients remained
      symptomatically improved and no myocardial infarction, stroke, or death was
      observed. Five-month angiographic reassessment revealed an in-stent restenosis
      rate of 41%, which was higher in vessels < or = 2.5 mm in size (47 vs. 33% for
      vessels > 2.5 mm, p = 0.2747). CONCLUSIONS: In selected patients with small
      native coronary vessels < 3.0 mm in diameter, angiography-guided optimal stent
      placement is associated with a low risk of stent thrombosis and bleeding
      complications. However, the in-stent restenosis rate is high with the stents used
      in this study.

PMID- 9259165
TI  - Atrial natriuretic peptide levels after different types of inferior wall
      myocardial infarction.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) is released from cardiac atrium
      secondary to increased atrial pressure. The plasma levels of ANP have been found
      to be related to short- and long-term prognosis after acute myocardial infarction
      (MI). The purpose of the present study was to investigate the plasma levels of
      ANP in three groups of patients with inferior wall acute MI classified according
      to ST-segment depression in the precordial leads. METHODS: The study population
      consisted of 18 patients with inferior wall acute MI classified into three types:
      Type 1 = no precordial ST-segment depression (7 patients), Type 2 = sum of ST
      segment depression in leads V1 to V3 equal to or more than the sum of ST-segment
      depression in leads V4 to V6 (4 patients), and Type 3 = maximal precordial ST
      segment depression in leads V4 to V6 (7 patients). RESULTS: Radioimmunoassay
      showed that plasma ANP levels were significantly higher in patients with Type 3
      acute inferior wall myocardial infarction compared with those with Types 1 and 2
      (313.1 +/- 233, 73.0 +/- 27.5), and 84 +/- 32.7 pg/ml, respectively, p = 0.018).
      CONCLUSIONS: Plasma ANP levels are higher in patients with Type 3 acute inferior
      wall MI compared with patients with Types 1 and 2. These findings, together with
      earlier ones, may contribute to our understanding of the pathophysiology of the
      presence of ST-segment depression in the precordial leads in inferior wall acute
      MI.

PMID- 9259166
TI  - Atrioventricular sequential pacing in cardiac amyloidosis: an acute Doppler
      echocardiographic and catheterization hemodynamic study.
AB  - BACKGROUND AND HYPOTHESIS: Congestive heart failure due to cardiac amyloidosis is
      often refractory to conventional medical management and is associated with a high
      mortality rate. Recently, dual-chamber pacemaker implantation has been proposed
      as a therapeutic option in the management of patients with certain forms of
      cardiomyopathy with persistent heart failure symptoms, despite optimal medical
      therapy. The present study evaluates the acute hemodynamic response to
      atrioventricular (AV) pacing in patients with cardiac amyloidosis who presented
      with refractory heart failure symptoms. METHODS: Three patients with medically
      refractory heart failure due to cardiac involvement of amyloidosis underwent a
      simultaneous cardiac catheterization/Doppler echocardiography study with acute AV
      sequential pacing at varying AV intervals. RESULTS: During pacing at various AV
      intervals, all patients showed an increased in their filling pressures and either
      no change or decline in their cardiac index. CONCLUSION: The current study
      demonstrates an absence of acute hemodynamic with AV sequential pacing in
      patients with amyloid heart disease and medically refractory heart failure
      symptoms.

PMID- 9259167
TI  - Contemporary issues in rate-adaptive pacing.
AB  - This review addresses a number of questions pertaining to contemporary rate
      adaptive pacemakers that include the role of dual sensor systems, sensor blending
      and cross-checking, automaticity, nonrate-related sensor functions, prevention of
      arrhythmias, and several other areas of clinical importance.

PMID- 9259168
TI  - Nonneoplastic diseases of aorta and pulmonary trunk--Part I.
AB  - This five-part review focuses on selected nonneoplastic diseases of the aorta and
      pulmonary trunk. Because many more diseases affect the aorta compared with the
      pulmonary trunk and right and left main pulmonary arteries, most of this review
      will be devoted to disorders of the aorta. Part I of this five-part review
      discusses general concepts of aorta anatomy and aortic dissection.

PMID- 9259169
TI  - Hyperglycemia-induced angina pectoris in a patient with diabetes mellitus.
AB  - A patient with diabetes mellitus and coronary artery disease presented with
      recurring episodes of worsening angina not associated with angiographic changes.
      Correlation with blood sugars demonstrated that angina would occur during
      episodes of hyperglycemia. During cardiac catheterization, coronary vascular
      responses including coronary flow reserve and responses to atrial pacing were
      measured with a Doppler flow wire before and following a glucose challenge.
      Coronary microvascular responses were impaired by hyperglycemia.

PMID- 9259170
TI  - Early presentation of dilated cardiomyopathy as a part of seroconversion illness
      in human immunodeficiency virus infection.
AB  - It has been debated whether dilated cardiomyopathy seen in patients with acquired
      immune deficiency syndrome is caused by the virus itself or by the combination of
      other factors such as presence of opportunistic pathogens and/or severe
      immunosuppression. This paper describes the first reported case of a patient with
      human immunodeficiency virus (HIV) infection presenting with dilated
      cardiomyopathy during his acute seroconversion illness. Presence of cardiac
      involvement at a very early stage of HIV infection with no evidence of
      opportunistic infections, or immunosuppression with high CD4 count indicates that
      HIV may itself be a cardiac pathogen. This case also illustrates the importance
      of testing for HIV infection as part of the assessment of any patient presenting
      with myocarditis or dilated cardiomyopathy.

PMID- 9259171
TI  - Joseph Skoda.

PMID- 9259172
TI  - Can estrogens prevent neurodegeneration?
AB  - Estrogen replacement therapy appears to have significant beneficial effects on
      cognition and mood in the elderly. In recent studies, its use has been associated
      with short term symptomatic cognitive improvement and with a decreased risk of
      (or a delay in) developing Alzheimer's disease (AD). Clinical reports are
      supported by substantial basic scientific evidence of the neuroprotective effects
      of estrogens. Their specific effects on dementia and cognitive impairment remain
      to be delineated. Ongoing randomised trials in AD will only provide information
      on the symptomatic effects of estrogen. Although basic research will progress,
      there is currently sufficient knowledge to promote active clinical research on
      the possible disease-modifying or neuroprotective effects of estrogens in the
      elderly.

PMID- 9259173
TI  - Pharmacological management of arrhythmias in the elderly.
AB  - The incidence of cardiac arrhythmia increases with advancing age, as does the
      prevalence of structural heart disease. Serious arrhythmias, such as sustained
      ventricular tachycardias, are uncommon in elderly patients, but nonsustained
      ventricular tachycardias and atrial fibrillation are relatively frequent. The
      first step in the treatment of supraventricular and ventricular arrhythmias is
      the identification of an underlying (cardiac) disease, which should be treated
      appropriately. Patients with supraventricular arrhythmias who do not have a
      severe underlying cardiac disease may be treated with antiarrhythmic drugs to
      prevent recurrences of the arrhythmia. In selected patients, radiofrequency
      catheter ablation may nowadays be the first-line therapeutic strategy. In elderly
      patients with underlying cardiac disease who are experiencing non-life
      threatening arrhythmias, antiarrhythmic drugs are generally discouraged because
      of the risk of proarrhythmic effects or other adverse events. In patients
      experiencing life-threatening ventricular arrhythmias, beta-blockers may be the
      first-line therapy. If these drugs are not effective, or cause adverse effects,
      class III or class IC antiarrhythmic drugs may be used as alternatives.
      Radiofrequency ablation is only moderately effective for haemodynamically stable
      ventricular tachycardias occurring post-myocardial infarction, but may be an
      option in drug-refractory patients.

PMID- 9259174
TI  - Depression and myocardial infarction. Implications for medical prognosis and
      options for treatment.
AB  - Depression and myocardial infarction (MI) are closely related. Various
      pathophysiological mechanisms could link depression to MI, and the different
      pharmacological and nonpharmacological treatment modalities that could be used
      have both advantages and disadvantages. Unlike tricyclic antidepressants, the
      selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) lack
      arrhythmogenic effects. In addition to their beneficial effects on depression,
      SSRIs have positive effects on psychological factors such as anxiety and mood
      disturbances that are not uncommon in patients who have had an MI. Therefore,
      these drugs should be preferentially considered for the treatment of depression
      in MI patients. Studies to further determine the impact of depression on the
      outcome of MI, and the place of different treatment modalities, are in progress.

PMID- 9259175
TI  - Antidepressant use in the elderly. Current status of nefazodone, venlafaxine and
      moclobemide.
AB  - Depression is a significant problem in the elderly. Because of aging-related
      pharmacokinetic and pharmacodynamic changes, it is not possible to automatically
      extrapolate findings on the efficacy or tolerability of antidepressants from
      younger to older populations. Venlafaxine inhibits both noradrenaline
      (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake. Analysis of
      data from phase II and III trials showed that venlafaxine was comparably
      effective in the young and in a subset of over 350 elderly patients. Venlafaxine
      dosage needs to be lowered in the elderly with renal impairment. As a weak
      cytochrome P450 (CYP) inhibitor, it is unlikely to have clinically significant
      drug interactions. Venlafaxine may be associated with some increase in supine
      diastolic blood pressure, especially at dosages above 150 mg/day. Nefazodone is a
      serotonin uptake inhibitor and serotonin 5-HT2A receptor antagonist. Pooled
      analysis of about 250 patients found nefazodone to be effective in elderly
      individuals with moderate or severe depressive symptoms, with or without
      melancholia, in both primary and recurrent episodes. Nefazodone clearance is
      reduced in patients with hepatic impairment, and plasma concentrations have been
      reported to be higher in the elderly. Nefazodone is an inhibitor of the CYP3A4
      family. There does not appear to be any increase in the frequency or severity of
      adverse effects in the elderly. Moclobemide is a selective inhibitor of monoamine
      oxidase type A. Studies in the elderly have found it to be well tolerated and
      meta-analysis has shown it to be comparably effective in young and elderly
      populations, and comparable to other antidepressants in terms of efficacy.
      Neither age nor renal impairment necessitate dosage adjustment, but hepatic
      impairment does necessitate dosage reduction. Dietary restrictions are not
      required. Overall, there is a relative paucity of data on the tolerability and
      efficacy of newer antidepressants in the elderly, especially those with
      concomitant medical disorders. Data that are available indicate that venlafaxine,
      nefazodone and moclobemide have comparable efficacy in older and younger
      patients.

PMID- 9259176
TI  - Current and future therapies for myasthenia gravis.
AB  - Myasthenia gravis (MG) is undoubtedly the most thoroughly understood of all human
      autoimmune diseases. The basic defect in the disease is a decrease in the number
      of available acetylcholine receptors (AChR) at neuromuscular junctions caused by
      an antibody-mediated autoimmune attack. Current treatments aimed at restoring the
      available AChR, depleting the autoantibodies or suppressing the immune system
      have been so effective that most patients can lead normal lives. However,
      prolonged drug treatment is required, and this carries a potential risk of drug
      toxicity and, in the case of immunosuppressants, systemic immunosuppression. The
      ideal treatment for MG would eliminate only the abnormal autoimmune response
      without interfering with the immune system. During the past 20 years, impressive
      advances have been made in our understanding of the immunology and molecular
      biology of MG. Accordingly, it should be possible to design rational and immune
      based therapies in the future. In this article, we briefly review the current
      treatment modalities for MG, and discuss the prospects for immunotherapy.

PMID- 9259179
TI  - Mechanical stress-cell function relationships in renal cells.

PMID- 9259178
TI  - Treatment of multiple myeloma in elderly patients. New developments.
AB  - The median of survival among patients with multiple myeloma (MM) is about 30
      months from the onset of treatment. Tumour burden and a range of other
      parameters, such as C-reactive protein levels, the plasma cell labelling index
      and beta2-microglobulin levels, can be used to assign patients to favourable and
      unfavourable prognostic groups. Conventional chemotherapy consists of melphalan
      and prednisone, and is as effective as moderately intensive cytotoxic drug
      regimens. Although second-line chemotherapy is initially effective, all patients
      eventually die. Maintenance therapy will interferon-alpha prolongs the plateau
      phase of the disease, but its effects on overall survival are minimal. One of the
      promising developments in the treatment of MM has been the introduction of high
      dosage chemotherapy, which can now be safely administered when stem cells are
      used for haematological recovery. Autologous bone marrow transplantation has been
      shown to produce a significant improvement in survival compared with conventional
      therapy. Several studies are under way that are examining the effects of multiple
      courses of high dosage chemotherapy together with peripheral stem cell support.
      Purging of autologous stem cell harvests will be performed in the near future to
      minimise contamination with myeloma cells. It is now feasible to use high dosage
      chemotherapy, with the support of granulocyte colony-stimulating factor
      stimulated whole blood, in selected elderly patients. Besides the promising
      development of intensive therapy, a number of other treatment strategies have
      emerged, including treatment with monoclonal antibodies against interleukin-6 and
      multidrug resistance-modulating agents. Better supportive care can be provided
      for some patients by using epoetin (recombinant human erythropoietin), and the
      sequelae of lytic bone lesions can be ameliorated through the use of
      bisphosphonates.

PMID- 9259180
TI  - H+, K(+)-ATPASE in the kidney: localization and function in the nephron.
AB  - In the past few years, many studies aimed at characterizing the localisation, the
      molecular nature, and the pharmacological and functional properties of renal H+,
      K(+)-ATPases. These studies included: (1) molecular cloning (by homology with
      other known P-type K(+)-ATPases) and expression of H+, K(+)-ATPase alpha-subunits
      from amphibian and mammalian epithelia; (2) kinetic and pharmacological
      characterization of K(+)-ATPase activities different from Na+, K(+)-ATPase in
      single segments of rat nephron, and (3) analysis of K+ and/or H+ transport in
      isolated collecting ducts from rat or rabbit kidney. The present paper summarizes
      these data with a special emphasis on those which demonstrate the existence along
      the mammalian nephron of several forms of H+, K(+)-ATPase displaying distinct
      biochemical, pharmacological and functional properties.

PMID- 9259181
TI  - Na+/H+ exchanger subtypes in the renal tubule: function and regulation in
      physiology and disease.
AB  - Four members of the Na+/H+ (NHE) exchange family are present in the renal tubule.
      NHE1, ubiquitously expressed, amiloride-sensitive and growth factor-activatable,
      is present in the basolateral membrane of most segments of the renal tubule. NHE2
      and NHE3 are present in the apical membrane of renal tubule segments, except the
      collecting duct. NHE4 is probably a basolateral isoform. NHEs are involved in
      multiple functions, cell pH and volume regulation, and transepithelial transport
      of NaCl, NaHCO3, and NH4+. The present review deals with the recent developments
      in the functions of NHEs, the effects of hormones, osmolality, acid base status,
      and potassium stores of Na+/H+ exchange at the cellular and molecular levels.
      Finally, the alterations of NHE activities in some renal disease processes are
      briefly discussed.

PMID- 9259177
TI  - Drugs for the treatment of impotence.
AB  - Penile erection is a complex neurovascular event that represents a balance
      between corporal smooth muscle relaxation and contraction. This balance is
      determined by the interaction between proerectile and antierectile
      neurotransmitters. It is believed that nitric oxide is the primary erectogenic
      neurotransmitter and that noradrenaline (norepinephrine) is the primary
      erectolytic neurotransmitter. There are a number of pharmacological approaches to
      the management of erectile dysfunction and manipulation of the neurotransmitter
      systems. These involve direct delivery of drugs into the erectile chambers
      (intracavernosal injection therapy), administration of medications into the
      urethra (transurethral delivery), application of medications to the skin
      (transdermal delivery) and it is hoped that oral agents will be available in the
      very near future. This article reviews the world literature on the medications
      that have been investigated to date and their delivery routes.

PMID- 9259182
TI  - Messenger RNA for enzymes of ornithine and polyamine metabolism are selectively
      underexpressed in kidney of 5/6 nephrectomized rats.
AB  - Altered nitrogen metabolism is a feature of chronic renal failure (CRF). The
      present study examined changes in renal expression of mRNA for enzymes involved
      in ornithine and polyamine metabolism, i.e. ornithine aminotransferase (OAT),
      ornithine decarboxylase (ODC), and S-adenosylmethionine synthetase (S-ADMase),
      during the early phase of renal insufficiency in rats after 5/6 nephrectomy (Nx).
      Involvement of androgens, the most potent stimulators of renal ODC, in these
      changes, was also evaluated inasmuch as testoseronemia is known to be
      significantly decreased in male uremic subjects. The abundance of mRNA was
      evaluated by quantitative Northern analysis of total RNA extracted from the
      remnant kidney of male or female Nx rats. The level mRNA for ODC was depressed by
      76, 83, and 79%, that for OAT by 60, 76 and 63%, and that for S-ADMase by 37, 58
      and 30%, at, respectively, 2, 7 and 35 days after Nx, in both male and female
      rats. ODC but not OAT enzyme activity was decreased. The expression of
      glyceraldehyde-3-phosphate dehydrogenase was only slightly lowered and that of c
      myc was unaltered. Renal polyamine content of the remnant kidney was unchanged.
      It is concluded that in CRF: (1) intrarenal ornithine metabolism and polyamine
      biosynthesis are greatly impaired; (2) decreased androgens are not involved in
      these changes; (3) increased ODC is not a prerequisite for kidney hypertrophy;
      (4) extrarenal polyamines accumulation into the remnant likely compensates for
      defective renal biosynthesis.

PMID- 9259183
TI  - Transforming growth factor-beta 1 regulates the expression of Pax-2, a
      developmental control gene, in renal tubule cells.
AB  - BACKGROUND/AIMS: The pattern-forming event of kidney tubulogenesis is initiated
      by the inductive transition of mesenchymal cells to epithelial phenotype; a
      transition that is critically dependent on the regulated expression of the
      developmental control gene, Pax-2. Because of a defined role in in vitro renal
      tubulogenesis, the effects of epidermal growth factor (EGF), transforming growth
      factor (TGF)-beta 1 and retinoic acid on Pax-2 gene expression in proximal tubule
      cells (PTC) were evaluated. METHODS: Rabbit PTC were isolated and grown in tissue
      culture. Under confluent quiescent conditions, the effect of various factors on
      Pax-2 gene expression was assessed by Northern blot analysis. To assess whether
      the effect of TGF-beta 1 to alter Pax-2 gene expression was due to
      transcriptional or posttranscriptional events, nuclear run-on assays were also
      undertaken. RESULTS: Under control, confluent growth conditions, PTC expressed
      high levels of Pax-2. A 24-hour exposure to EGF (10 nM), a potent mitogen of PTC,
      increased this level of expression. In contrast, Pax-2 gene expression was
      suppressed by treating PTC with retinoic acid (10 mM), a well-described
      differentiating factor, and with TGF-beta 1 (10 ng/ml), a recognized
      antiproliferative agent for these cells, which suggests that Pax-2 has a role in
      renal cell proliferation. The mechanism of the effect of TGF-beta 1 on Pax-2 mRNA
      levels was further detailed. TGF-beta 1 did not affect Pax-2 transcription rates,
      as assessed by nuclear run-on assays; however, in a dose-dependent manner, it
      diminished the stability of Pax-2 mRNA. At a concentration of 10 ng/ml, TGF-beta
      1 reduced Pax-2 mRNA stability from a control half-life of 120 min to a half-life
      of less than 60 min. CONCLUSION: This study demonstrates that various soluble
      inductive factors affect Pax-2 gene expression in renal tubule cells. Also, TGF
      beta 1 downregulates Pax-2 gene expression through a posttranscriptional process,
      an acknowledged mechanism for modulating important growth regulatory gene
      products.

PMID- 9259184
TI  - Decreased PMN accumulation and glomerular damage by clodronate liposome treatment
      in PMN-dependent anti-GBM nephritis in mice.
AB  - BACKGROUND: Intravenous administration of clodronate (dichloromethylene
      bisphosphate)-containing liposomes (clodro-L) has been reported to induce
      selective depletion of tissue macrophages (M phi) with little or no effect on
      polymorphonuclear granulocytes (PMN). Therefore, we used clodro-L treatment to
      study the role of M phi in a PMN-dependent model of anti-glomerular basement
      membrane (GBM) nephritis. METHODS: C57BL/6J mice received clodro-L i.v. at days 
      2 and -1 before i.v. injection of anti-GBM antibodies. The albuminuria of the
      first 24 h was measured by radial immunodiffusion in 18 hour urine samples and
      glomerular changes were studied histologically and immunohistologically. RESULTS:
      Treatment with clodro-L, in doses that adequately destroyed the Kupffer cells,
      failed to reduce glomerular M phi numbers, but markedly inhibited glomerular PMN
      accumulation. Compared to control mice, clodro-L-pretreated C57BL/6J mice showed
      considerable reduction of both albuminuria and glomerular damage at day 1 after
      injection of rabbit anti-GBM antibody. CONCLUSIONS: In this PMN-dependent model,
      the inhibitory effect of clodro-L treatment on the development of nephritis very
      likely due to the inhibition of glomerular PMN accumulation. Our results indicate
      the clodro-L treatment as a method of selective M phi depletion has its
      limitations, especially in models in which PMN are involved as effector cells.

PMID- 9259185
TI  - Three-dimensional organization and segmental ultrastructure of rat proximal
      tubules.
AB  - AIMS: To provide a 3-D description and basic morphometric data along the course
      of subcapsular proximal tubules. METHODS: Proximal convoluted (PCT) and straight
      (PST) tubules were analyzed in series of up to one thousand 4-micron sections of
      perfusion-fixed rat renal cortex. Nine proximal tubules were traced through the
      sections by computer-assisted 3-D reconstruction. Selected sections were
      reembedded and resectioned for ultrastructural morphometry. RESULTS: Subcapsular
      PCTs (n = 3) had a total length of 12.0 +/- 0.2 mm (SEM), formed tight clusters
      and contacted the renal surface from 5 to 10 times. In contrast, mid-cortical
      tubules (total PT length 11.6 +/- 0.1 mm) and in particular deep cortical tubules
      (total PT length 12.1 +/- 0.9 mm) extended laterally and intermingled
      considerably with neighboring tubules. Epithelial height gradually decreased from
      around 11 microns in the PCT to 7.5 microns in the end of the PST. Brush-border
      height was around 4 microns in the first PT segment (S1), 2.3 microns in the
      second segment (S2) and 4.5 microns in the end of the proximal tubule. Tubular
      wall volume, excluding microvilli, decreased from around 1,450 micron3/microns
      tubule length in early PCT to 825 micron3/microns in terminal PST. CONCLUSIONS:
      The results provide, at precisely defined nephron levels, quantitative
      ultrastructural data relevant to transport physiology.

PMID- 9259186
TI  - Production of monocyte chemoattractant protein-1 by cultured glomerular
      epithelial cells: inhibition by dexamethasone.
AB  - Glomerular epithelial cells (GECs) have been shown to be one class of target
      cells in immunological and nonimmunological glomerular injury of
      glomerulonephritis, some cases of which are accompanied by infiltration of
      glomeruli by monocytes/macrophages. In this study we tested whether GECs in
      culture produce monocyte chemoattractant protein-1 (MCP-1), a potential molecule
      responsible for monocyte recruitment in inflammation, and whether the production
      is inhibited by glucocorticoid. GECs were obtained from outgrowth of rat
      glomeruli. Levels of MCP-1 mRNA and protein were determined by Northern blot
      analysis and ELISA, respectively. Northern blot analysis revealed the expression
      of MCP-1 mRNA in cytokine-treated GECs. The expression of MCP-1 mRNA was
      inhibited by dexamethasone. Quantitative analysis by ELISA confirmed the
      production of MCP-1 protein by GECs and the inhibitory effect of dexamethasone.
      These results indicate that cytokine-treated GECs produce and secrete MCP-1 and
      that the MCP-1 production is inhibited by dexamethasone. We suggest that MCP-1
      produced by GECs may play a role in the recruitment of monocytes/macrophages in
      glomerulonephritis and that the therapeutic effect glucocorticoid on the disease
      might include the inhibition of the production of MCP-1.

PMID- 9259187
TI  - Reduced aminolevulinate dehydrase activity in rats with functional renal failure
      induced by cyclosporin A.
AB  - Patients with chronic failure evidence various abnormalities in heme metabolism,
      primarily erythrocyte aminolevulinate dehydrase hypoactivity and increased plasma
      and erythrocyte porphyrin levels. Such abnormalities have also been observed in
      animals with both acute and chronic experimental renal failure. The aim of this
      work was to study these parameters of porphyrin metabolism in an experimental
      model of functional renal failure. A group of 11 male Wistar rats received 13
      doses (25 mg/kg body weight/day) of cyclosporin A. Serum creatinine did not vary,
      but the blood urea nitrogen levels increased and a significant decrease in the
      creatinine clearance was observed. The drug also caused a marked decrease in the
      erythrocyte aminolevulinate dehydrase activity, a slight reduction of the
      hematocrit value, and increased levels of blood porphyrins. The plasma of treated
      rats showed capacity to inhibit aminolevulinate dehydrase activity when incubated
      in vitro with erythrocytes from control rats. Porphyrin metabolism remained
      unchanged in the liver. The daily diuresis was significantly decreased in the
      cyclosporin as compared to the control group; however, the porphyrinuria showed
      no changes. The derangements in the erythrocyte heme biosynthesis pathway
      observed in patients with chronic renal failure are reproducible in an
      experimental model of cyclosporin A-induced functional renal failure.

PMID- 9259188
TI  - Escherichia coli porin induces proinflammatory alterations in renal tubular
      cells.
AB  - BACKGROUND/AIMS: Several bacterial components may contribute to the development
      of renal injury during Gram-negative sepsis. In the present study, we evaluated
      the proinflammatory effect on cultured human proximal tubular epithelial cells
      (PTEC) of a 36-kD porin purified from escherichia coli METHODS: PTEC were
      stimulated with E. coli porin to evaluate 45Ca2+ influx, cytoskeleton changes,
      generation of reactive oxygen species (ROS) as detected by chemiluminescence and
      cytochrome c reduction. Production of TNF-alpha, IL-6 and IL-8 was evaluated at
      the mRNA and protein levels. RESULTS: Stimulation of PTEC with porin was followed
      by a rapid and sustained 45Ca2+ influx and by an altered distribution of actin
      fibers and of vinculin streaks. Porin was able to induce generation of ROS and
      production of proinflammatory cytokines from PTEC. TNF-alpha production peaked at
      6 h after exposure to porin and preceded that of IL-6 and IL-8. CONCLUSIONS: E.
      coli porin - at doses attainable in vivo - appears to stimulate PTEC to produce
      ROS and cytokines. Porin-induced PTEC activation may contribute to renal injury
      in the course of Gram-negative infection.

PMID- 9259190
TI  - Studies on the efficacy and prognostic significance of drug therapy of
      ventricular tachyarrhythmias.

PMID- 9259189
TI  - Early effects of streptozotocin-induced diabetes on insulin-like growth factor-I
      in the kidneys of growth hormone-transgenic and growth hormone-deficient dwarf
      mice.
AB  - BACKGROUND: The renal growth and hyperfiltration observed in humans and animals
      with early diabetes might be dependent on growth hormone (GH) and insulin-like
      growth factor (IGF)-I. The aim of this study was to investigate the early changes
      in kidney IGF-I in experimental diabetes in mice transgenic for bovine GH and in
      genetically GH-deficient Ames dwarf mice. METHODS: At 2, 4 and 8 days after a
      single intraperitoneal injection with streptozotocin, animals were weighted, bled
      and killed; plasma was analyzed for glucose and IGF-I. IGF-I levels were
      determined in tissue from snap-frozen kidney and liver. RESULTS: Body weight
      decreased significantly after the induction of diabetes. Kidney weight increased
      significantly in GH-transgenic, but not in normal or dwarf mice. Plasma IGF-I was
      significantly decreased at day 2 in GH-transgenic and normal mice, while liver
      IGF-I was increased at day 4 in all mice. Kidney IGF-I increased significantly in
      normal and GH-transgenic mice and was increased more than 3-fold at day 4 in GH
      transgenic mice. In dwarf mice, no kidney IGF-I was detectable. CONCLUSION: The
      diabetes-induced increase in renal IGF-I is dependent on the presence of GH. GH
      deficiency may protect diabetic animals from early changes in the kidney.

PMID- 9259191
TI  - Acute myocardial infarction without thrombolytic therapy: beneficial effects of
      magnesium sulfate.
AB  - Only one third of hospitalized patients with acute myocardial infarction (AMI)
      receive thrombolytic therapy despite its proven benefits on outcomes. Elderly
      patients, have a greater risk of death during myocardial infarction; however,
      thrombolytic therapy appears to be less used in these patients, as compared to
      the general AMI-patients. In order to evaluate the impact of magnesium
      supplementation in AMI-patients without thrombolytic therapy, 194 patients
      participated in a prospective, randomized and placebo-controlled study: 96
      patients received a 48-hour intravenous magnesium sulfate and 98 isotonic glucose
      as placebo. Magnesium infusion reduced the incidence of arrhythmias, congestive
      heart failure and in-hospital-mortality compared with placebo (27 vs. 40%, p =
      0.04; 18 vs. 23%, p = 0.27; 4 vs. 17%, p < 0.01, respectively); in the subgroup
      of elderly patients (> 70 years), the benefit was also obvious (42 vs. 50%; 18
      vs. 25%; 9 vs. 23%, p = 0.09, respectively). These data suggest that intravenous
      magnesium supplementation might be justified in order to reduce myocardial damage
      and mortality rate in subsets of high-risk patients such the elderly and/or
      patients not suitable for thrombolysis. Additional trials appear to be indicated
      to evaluate the potential benefit of magnesium in well defined specific subsets
      of AMT-patients.

PMID- 9259192
TI  - Molecular basis of HNPCC: mutations of MMR genes.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is inherited as a dominant
      disorder caused by germline defects in one of at least four mismatch repair (MMR)
      genes. Two of these genes, hMSH2 and hMLH1, account for the vast majority of the
      germline mutations in HNPCC kindreds, whereas hPMS1 and hPMS2 are mutated in only
      few families. MMR genes also are susceptible to somatic mutations in sporadic
      tumors. The mutational spectrum of the MMR genes shows no predominant type of
      mutation. Furthermore, the mutations are spread throughout the length of the
      genes, with no significant hot spots. Identification of MMR genes as the cause of
      HNPCC made presymptomatic diagnosis a reality. However, the presence of multiple
      genes and the heterogeneity of mutations present challenges to the development of
      diagnostic tests for this disease.

PMID- 9259193
TI  - Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia.
AB  - The ataxia-telangiectasia mutated (ATM) gene, which is mutated in the autosomal
      recessive disorder ataxia-telangiectasia (AT), was isolated in 1995 by positional
      cloning. Although in vitro cell fusion studies had suggested that AT was
      genetically heterogeneous, all AT patients studied to date have been found to
      harbor mutations in the ATM gene. More that 100 ATM mutations occurring in AT
      patients have been documented. The mutations are broadly distributed throughout
      the ATM gene. Except for patients from families with known consanguinity, most AT
      patients are compound heterozygotes. The majority (> 70%) of mutations are
      predicted to lead to protein truncation. A significant number of the reported
      mutations affect mRNA splicing with at least half of the coding exons (32/62)
      having been observed to undergo exon skipping. The large size of the ATM gene, 66
      exons spanning approximately 150 kb of genomic DNA, together with the diversity
      and broad distribution of mutations in AT patients greatly limits the utility of
      direct mutation screening as a diagnostic tool, or method of carrier
      identification, except where founder effect mutations are involved.

PMID- 9259195
TI  - Spectrum of LDL receptor gene mutations in heterozygous familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia by usual definition reflects mutations of the LDL
      receptor gene. Extensive molecular characterization of mutations ascertained
      mainly through homozygotes (the Dallas collection) has been presented by Hobbs et
      al. (Hum Mutat 1:445-446, 1992). This paper catalogues a spectrum of 134
      mutations (27 novel mutations in 45 patients, 24 previously described mutations
      in 89 patients) ascertained through heterozygotes from the analysis of 791
      patients with definite, probable, or possible FH, mainly from the UK, using high
      throughput modifications of the single-strand conformation polymorphism
      technique. From a composite database of LDL receptor gene mutations complied from
      these two sets and from the literature, deductions are made about ascertainment
      bias, mutation rates, and molecular heterogeneity. Calculations suggest that
      there may be a large number of rare amino acid variants in the general population
      not causing classic FH. Approaches to, and feasibility of, molecular diagnostics
      are considered.

PMID- 9259194
TI  - Rapid characterization of the variable length polythymidine tract in the cystic
      fibrosis (CFTR) gene: association of the 5T allele with selected CFTR mutations
      and its incidence in atypical sinopulmonary disease.
AB  - The CFTR intron 8 variable length polythymidine tract modulates the cystic
      fibrosis (CF) phenotype associated with the mutation R117H. To explore whether
      other mutations reside on multiple intron 8 backgrounds with discernible impacts
      on phenotype, we developed an allele-specific PCR assay to characterize this
      locus. Our approach types samples rapidly without the use or radioisotopes.
      Polythymidine alleles were identified for mutations either associated with a wide
      range of clinical phenotypes (R117H, R347P, G85E, D1152H, R334W, 2789 + 5 G > A,
      3849 + 10kb C > T), and/or located at hypermutable CpG loci (R117H, 3845 + 10kb C
      > T, R553X, R334W, S945L and R75Q). R117H was detected in cis with each of three
      alleles (5T, 7T, 9T) at the intron 8 locus. The novel R117H-9T association was
      detected in a 10-month African-American male with borderline-to-mildly elevated
      sweat chloride values (approximately 50-66 mEq/L). All other mutations studied
      were associated with 7T except 3849 + 10kb C > T, which was detected on both 7T
      and 9T backgrounds, but not 5T. Three individuals with a delta F508/3849 + 10kb C
      > T genotype were 9T,9T and had pancreatic sufficiency and normal sweat chloride
      values, whereas 15 others who carried 3849 + 10kb C > T on a 7T background had
      variable pancreatic function (sufficient, n = 12, insufficient, n = 3), and
      variable sweat chloride values (normal, n = 12, elevated, n = 3). Surprisingly,
      when not associated with known CFTR mutations, 5T was detected with elevated
      frequency among individuals with sinopulmonary disease of ill-defined etiology,
      but with some characteristics of variant CF. In summary, the 5T allele was not
      found in cis with CF-causing mutations besides R117H, but an elevated 5T allele
      frequency in variant CF patients suggests 5T may be associated with disease in
      some situations.

PMID- 9259196
TI  - Glycogenosis type II: a juvenile-specific mutation with an unusual splicing
      pattern and a shared mutation in African Americans.
AB  - The recessively inherited deficiency of acid alpha-glucosidase (GAA) called
      Glycogenosis Type II is expressed as three different phenotypes: infantile,
      juvenile, and adult. At the molecular level, infantile and adult forms of the
      disease have been extensively studied, but little is known regarding the genetic
      defects associated with the juvenile form. We describe a novel mutation that
      defines the intermediate juvenile phenotype in a compound heterozygous patient. A
      transversion of t to g in intron 6 at position -22 creates a cryptic acceptor
      site and results in unusual splicing abnormality: insertion of 21 nucleotides of
      the intronic sequence into mRNA and removal of exon 6 without disruption of the
      reading frame. The second mutation, Arg854Stop in exon 18, had been previously
      identified in another African-American patient (Hermans et al., 1993a). Family
      study indicates that a silent allele harboring the Arg854Stop mutation in our
      patient is inherited from the patient's father, who is also African-American,
      thus suggesting a common mutation in this population.

PMID- 9259197
TI  - Geographic distribution and regional origin of 272 cystic fibrosis mutations in
      European populations. The Biomed CF Mutation Analysis Consortium.
AB  - The geographic distribution of 272 cystic fibrosis (CF) mutations has been
      studied by assessing the origin of 27,177 CF chromosomes from 29 European
      countries and three countries from the North of Africa. The most common mutations
      are delta F308 (66.8%), G542X (2.6%), N1303K (1.6%), G551D (1.5%) and W1282X
      (1.0%). The delta F508 mutation has the highest frequency in Denmark (87.2%) and
      the lowest in Algeria (26.3%). Mutation G542X is common in the Mediterranean
      countries, with a mean frequency of 6.1%. N1303K is found in most of the western
      and Mediterranean countries and has the highest frequency in Tunisia (17.2%). The
      wide distribution of these mutations suggests an ancient origin. G551D is common
      in north-west and central Europe, but is uncommon in other parts of Europe.
      W1282X has the highest frequency in Israel (36.2%), being also common in most
      Mediterranean countries and north Africa. Seventeen mutation have frequencies
      between 0.1 and 0.9%, 1717-1G-->A (0.83%), R553X (0.75%), R1162X (0.51%), 621 +
      1G-->T (0.54%) and 2183AA-->G (0.36%), being the most common ones. Some mutations
      reach relatively high frequencies in some extended geographic regions, such as
      mutation 394delTT in northern Europe (1.1-28.8%), R117H in northwestern Europe
      (1.3-3.0%), R553X in central Europe (1.1-24.4%), 1717-1G-->A in Belgium and
      France (1.1-5.3%), and 2183AA-->G in Italy and Greece (3.2%). Other mutations are
      only common in small regions: T338I (Sardinia), 711 + 1G-->T (Tunisia), R1162X
      (Algeria and north of Italy), 1609delCA (east of Spain), 1811 + 1.6kbA-->G
      (southeastern Spain), R1066C (Portugal), S549R (Algeria), R334W (Crete), 621 + 1G
      ->T (Central Greece), 3849 + 10kbC-->T (Israel), 2789 + 5G-->A (south of Greece),
      451 + 1G--A (Israel), R347P (south of Bulgaria), 1677delTA (south of Bulgaria and
      Turkey), G85E (south of Greece), R347H (Turkey), 3905insT (Switzerland), 1078delT
      (Brittany), 1898 + 1G-->A (Wales), A455E (The Netherlands), delta I507
      (Brittany), 3659delC (Sweden) and R560T (northern Ireland). Most of these
      mutations must have an origin and diffusion in the specific European population
      subgroup. Overall 55 mutations are common in one or several countries or regions
      of Europe and 217 mutations are rare with relative frequencies of lower than 1%
      in any of these regions and countries. This information might facilitate mutation
      analysis of CF in the different regions of Europe.

PMID- 9259198
TI  - Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary
      thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a
      role for imprinting.
AB  - The multiple endocrine neoplasia type 2 (MEN2) syndromes and Hirschsprung's
      disease (HSCR) are inherited neurocristopathies characterized by medullary
      thyroid carcinoma (MTC), pheochromocytoma, parathyroid disease, and
      gastrointestinal neuromatosis. Mutations in the RET proto-oncogene are the
      underlying cause of the MEN2 syndromes and some cases of HSCR. In this report, we
      show that Cys 618 Arg mutation cosegregates with familial MTC and HSCR in two
      Moroccan Jewish families in which no involvement of pheochromocytoma or
      parathyroidism was observed. A single haplotype shared by chromosomes bearing the
      Cys 618 Arg mutation in both families strongly suggests a founder effect for this
      mutation. We have observed in our and in several other previously reported
      families, an excess of maternal over paternal mutated RET alleles in offsprings
      affected by HSCR. We suggest that parental imprinting may play a role in the
      ethiology of HSCR caused by mutations in the RET protooncogene.

PMID- 9259199
TI  - Familial ligand-defective apolipoprotein B-100: simultaneous detection of the
      ARG3500-->GLN and ARG3531-->CYS mutations in a French population.
AB  - Familial ligand-defective apolipoprotein B-100 (FDB) is an autosomal dominant
      disorder leading to plasma LDL cholesterol elevation and coronary artery disease
      (CAD). Two specific mutations in the APOB gene--R3500Q and R3531C--induce FDB. We
      report an original method to detect both mutations simultaneously, based upon PCR
      mediated, site-directed mutagenesis and double restriction of a unique PCR
      product. With this method we have investigated the prevalence of these mutations
      in 1,040 French patients. The R3500Q mutation was found in five probands.
      Genotypes were determined for 10 APOB polymorphic markers and were consistent
      with the common European ancestral haplotype previously reported. The only
      exception was one FDB proband who did not harbor the 48 repeat allele of the
      3'HVR. Additionally, the first two R3531C mutations were identified in French
      probands. Genotypes were consistent with a previously reported haplotype,
      suggesting that this is another mutation of European ancestry.

PMID- 9259200
TI  - Three novel mutations of the PKD1 gene in Italian families with autosomal
      dominant polycystic kidney disease.

PMID- 9259201
TI  - Identification of a new mutation of the myosin VII head region in Usher syndrome
      type 1.

PMID- 9259204
TI  - Acute respiratory failure, mechanical ventilation, and ECMO/ECCO2R: quo vadis?

PMID- 9259203
TI  - Novel mutations of the P gene in type II oculocutaneous albinism (OCA2).

PMID- 9259205
TI  - Dietary protein restriction for retardation of progression of chronic renal
      failure: yes or no?

PMID- 9259202
TI  - Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism
      (OCA1).

PMID- 9259207
TI  - Subclavian vein stenosis: a potentially serious complication in chronic
      hemodialysis patients with permanent cardiac pacemakers.
AB  - We report on two hemodialyzed patients in whom subclavian and brachiocephalic
      vein stenosis secondary to permanent cardiac pacemakers led to massive congestive
      edema of the same arm after arteriovenous fistula/grafts were created.
      Therapeutic solutions regarding hemodialysis access are discussed in these
      patients with permanent pacemakers requiring hemodialysis.

PMID- 9259206
TI  - Which amino-acids do serum and hemofiltrate of critically ill patients with acute
      renal failure contain?
AB  - The removal of amino acids during continuous renal replacement therapies induces
      clinical problems. Previous studies on animals have shown nephroprotective
      (glycine, alanine) or negative effects (lysine) on renal function in occurrence
      of acute renal failure. Disturbed metabolism in acute renal failure needs
      adequate parenteral nutrition. On the other hand, experience with continuous
      renal replacement therapies of metabolic crises in inborn errors of metabolism
      indicate a good control of disturbed amino acid metabolism. The aim of our study
      was to find amino acids, that might play an important role in the pathogenesis,
      prognosis and detection of acute renal failure and severe illness, so far only
      estimated by lactic acid. Thirty-three probes (serum and hemofiltrate) were taken
      from patients, suffering with acute renal failure caused by septic shock, severe
      pancreatitis and hepatorenal syndrome, one hour after the beginning of
      extracorporal circulation, the conditions of treatment were standardized. The
      material was deproteinized and studied by the amino acid analyzer LBK 4251 Apha
      Plus (Pharmacia, Stockholm, Sweden), while the lactic acid concentration was
      determined in a standard laboratory. Proline, glycine, alanine, methionine and
      histidine showed a close relationship to the lactic acid levels, but these amino
      acids were an essential part of parenteral nutrition. A statistical relationship
      was also established in (amino acids with amide groups) asparagine, glutamine,
      citrulline, cystathionine and phosphoethanolamine. The mean values of most of the
      amino acids were higher than normal, but standard deviations were increased. The
      presence of these amino acids in hemofiltrate and the good sieving coefficients
      could mean that the better prognosis of critically ill patients in continuous
      renal replacement therapies may also be due to continuous control of amino acid
      levels (especially with amide groups).

PMID- 9259208
TI  - Development of intracoronary local adhesive delivery technique.
AB  - Acute coronary occlusion may occur in weak coronary atherosclerotic lesions,
      including dissection, ulceration or thrombus. In some cases of occlusion "bail
      out" is performed by using recently developed New Devices. However, these have
      not yet completely solved the problem to this end, we designed a new method of
      coronary revascularization, the Intracoronary Local Adhesive Delivery Technique,
      utilizing antithrombotic and absorbable adhesive injected locally into the
      fragile and morbid arterial wall using a drug delivery PTCA catheter more
      flexible than the existing New Devices. This adhesive strengthened and hardened
      the lesions. In this study, we examined the efficacy of making an adhesive
      cylinder in arteries of similar size to the coronary, through acute animal
      experiments using the existing clinical adhesives and drug delivery PTCA
      catheters and 12 femoral arteries of adult goats. We were successful in forming
      firm tunnels along the inside of six arteries, infused with approximately 0.04 ml
      Cyanoacrylate. These tunnels were observed with intravascular ultrasound (IVUS)
      imaging and evaluated microscopically. These results suggest the feasibility of
      this method as a new approach for making synthetic resinous stents.

PMID- 9259209
TI  - Polyurethane heart valve durability: effects of leaflet thickness and material.
AB  - A flexible trileaflet polyurethane valve has been made by dip-moulding leaflets
      directly onto an injection-moulded frame. The durability of this value is, in
      part, determined by the thickness of its leaflets. Leaflet thickness is also a
      major determinant of hydrodynamic function. This study examines valves (n = 31)
      with leaflets made of a polyetherurethane (PEU, n = 22) or a
      polyetherurethaneurea (PEUE, n = 9), of varying thickness distributions. The
      valves were subjected to accelerated fatigue test at 37 degrees C and failure
      monitored. Leaflet thicknesses ranged from 60 to 200 microns. PEU leaflet
      thickness bore no relationship to durability, which was less than 400 million
      cycles. PEUE valves, in contrast, exceeded 800 million cycles. Durability in PEUE
      valves was directly related to leaflet thickness (r = 0.93, p < 0.001), with good
      durability achieved with median leaflet thicknesses of approximately 150 microns.
      Thus polyurethane valves can be made with good hydrodynamic properties and with
      sufficient durability to consider potential clinical use.

PMID- 9259210
TI  - Assessment of an epoxy-fixed pericardial patch with or without ionically bound
      heparin in a canine model.
AB  - In this study, an epoxy-fixed porcine pericardial patch with or without ionically
      bound heparin was evaluated in a canine model as an alternative to the
      glutaraldehyde-fixed biological patch for clinical applications. To evaluate the
      effectiveness of this epoxy-fixed patch, a composite membrane composed of: an
      epoxy-fixed porcine patch with ionically bound heparin; a glutaraldehyde-fixed
      porcine patch with ionically bound heparin; an ePTFE polymeric patch; a polyester
      polymeric patch; an epoxy-fixed porcine patch without ionically bound heparin;
      and a glutaraldehyde-fixed porcine patch without ionically bound heparin was
      made. This membrane was assessed orthopically in a canine model. The early
      results (1 approximately 4 weeks post implant) revealed that the biological
      patches with ionically bound heparin had the mildest tissue reactions
      (inflammatory reaction, fibrosis, and adhesion) among all the test samples.
      However, by 12 weeks postoperatively, all the test samples had mild to severe
      tissue reactions. The order of tissue reactions with increasing severity was: the
      biological patches with ionically bound heparin, the biological patches without
      ionically bound heparin, and the polymeric patches. The results suggest that
      heparin may be used to reduce adhesion. Additionally, the epoxy-fixed tissue
      caused a relatively lower degree of inflammatory reaction than the glutaraldehyde
      fixed tissue.

PMID- 9259212
TI  - A novel field generator for magnetic stimulation in cell culture experiments.
AB  - A novel field generator specially designed to examine the influence of low
      frequency magnetic fields on specific cell material was constructed and
      characterized. The exposure unit described in this paper consists of a controller
      unit and three sets of coils. The field generator permits a precious definition
      of the revelant signal parameters and allows the superposition of alternating
      current (AC) and direct current (DC) magnetic fields. Critical system parameters
      were monitored continuously. The three sets of coils, each arranged in the
      Helmholtz Configuration were characterized. After data processing and
      visualization the results showed a constant and homogeneous field within the
      experimental area. The special coil design also allows their use in an incubator.

PMID- 9259211
TI  - Virtual extracorporeal circulation process.
AB  - Virtual instruments for an extracorporeal circulation (ECC) process were
      developed to simulate the reactions of a patient to different artificial
      perfusion conditions. The computer simulation of the patient takes into account
      the hydraulic, volume, thermal and biochemical phenomena and their interaction
      with the devices involved in ECC (cannulae dimensions, oxygenator and filter
      types, pulsatile or continuous pump and thermal exchangers). On the basis of the
      patient's initialisation data (height, weight, Ht) and perfusion variables (pump
      flow rate, water temperature, gas flow rate and composition) imposed by the
      operator, the virtual ECC monitors simulated arterial and venous pressure
      tracings in real time, along with arterial and venous flow rate tracings, urine
      production tracing and temperature levels. Oxyhemoglobin arterial and venous
      blood saturation together with other related variables (pO2, pCO2, pH, HCO3 are
      also monitored. A drug model which allows the simulation of the effect of
      vasodilator and diuretic drugs is also implemented. Alarms are provided in order
      to check which variables (pressure, saturation, pH, urine flow) are out of the
      expected ranges during the ECC simulation. Consequently the possibility of
      modifying the control parameters of the virtual devices of the ECC in run-time
      mode offers an interaction mode between the operator and the virtual environment.

PMID- 9259213
TI  - State-and sex-specific prevalence of selected characteristics--behavioral risk
      factor surveillance system, 1994 and 1995.
AB  - PROBLEM/CONDITION: High-risk behaviors (e.g., cigarette smoking, excessive
      alcohol consumption, and physical inactivity) and lack of preventive health care
      (e.g., screening for cancer) are associated with chronic disease- and injury
      related morbidity and mortality. States use the Behavioral Risk Factor
      Surveillance System (BRFSS) to collect data about these modifiable health
      behaviors and to monitor trends and changes in the prevalence of behavioral risk
      factors in state populations. BRFSS data also are used to monitor progress toward
      the year 2000 national health objectives. REPORTING PERIOD: 1994 and 1995.
      DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the
      civilian, noninstitutionalized, adult (persons > or =18 years of age) population.
      In 1994, 49 states and the District of Columbia participated in the BRFSS; in
      1995, 50 states participated. RESULTS: As in previous years, there were state
      specific variations in the prevalences of high-risk behaviors, awareness of
      certain medical conditions, use of preventive health services, and health-care
      coverage. Selected findings for 1995 were that 22.4% of adults reported being
      current cigarette smokers (range: 13.2%-27.8%); the percentage of adults who
      reported driving after drinking too much alcohol ranged from 0.6% to 5.2%
      (median: 2.3%); and among adults aged > or =65 years, 36.8% (range: 11.4%-46.6%)
      reported ever having had a pneumococcal vaccination and 59.2% (range: 44.2%
      70.0%) reported having had an influenza vaccination within the past 1 year.
      INTERPRETATION: State-specific variations in prevalence may reflect differences
      in population composition, socioeconomic factors, state laws enacted to
      discourage high-risk behaviors, levels of effort to screen for certain diseases
      and physiological conditions, and other factors. ACTION TAKEN: States continue to
      use the BRFSS to monitor risk factors associated with chronic disease- and injury
      related morbidity and mortality and to develop public health programs and
      policies to address these problems. BRFSS data continue to be important in
      assessing progress toward national year 2000 and state health objectives.

PMID- 9259215
TI  - Pregnancy-related mortality surveillance--United States, 1987-1990.
AB  - PROBLEM/CONDITION: The Healthy People 2000: National Health Promotion and Disease
      Prevention Objectives specifies goals of no more than 3.3 maternal deaths per
      100,000 live births overall and no more than 5.0 maternal deaths per 100,000 live
      births among black women; as of 1990, these goals had not been met. In addition,
      race-specific differences between black women and white women persist in the risk
      for pregnancy-related death. REPORTING PERIOD COVERED: This report summarizes
      surveillance data for pregnancy-related deaths in the United States for 1987
      1990. DESCRIPTION OF SYSTEM: The National Pregnancy Mortality Surveillance System
      was initiated in 1988 by CDC in collaboration with the CDC/American College of
      Obstetricians and Gynecologists Maternal Mortality Study Group. Health
      departments in the 50 states, the District of Columbia, and New York City
      provided CDC with copies of death certificates and available linked outcome
      records (i.e., birth certificates or fetal death records) of all identified
      pregnancy-related deaths. RESULTS: During 1987-1990, 1,459 deaths were determined
      to be pregnancy-related. The overall pregnancy-related mortality ratio was 9.2
      deaths per 100,000 live births. The pregnancy-related mortality ratio for black
      women was consistently higher than for white women for every risk factor examined
      by race. The disparity between pregnancy-related mortality ratios for black women
      and white women increased from 3.4 times greater in 1987 to 4.1 times greater in
      1990. Older women, particularly women aged > or =35 years, were at increased risk
      for pregnancy-related death. The gestational age-adjusted risk for pregnancy
      related death was 7.7 times higher for women who received no prenatal care than
      for women who received "adequate" prenatal care. The distribution of the causes
      of death differed depending on the pregnancy outcome; for women who died
      following a live birth (i.e., 55% of the deaths), the leading causes of death
      were pregnancy-induced hypertension complications, pulmonary embolism, and
      hemorrhage. INTERPRETATION: Pregnancy-related mortality ratios for black women
      continued, as noted in previously published surveillance reports, to be three to
      four times higher than those for white women. The risk factors evaluated in this
      analysis confirmed the disparity in pregnancy-related mortality between white
      women and black women, but the reason(s) for this difference could not be
      determined from the available information. ACTIONS TAKEN: Continued surveillance
      and additional studies should be conducted to assess the magnitude of pregnancy
      related mortality, to identify those differences that contribute to the
      continuing race-specific disparity in pregnancy-related mortality, and to provide
      information that policy makers can use to develop effective strategies to prevent
      pregnancy-related mortality for all women.

PMID- 9259214
TI  - Hysterectomy surveillance--United States, 1980-1993.
AB  - PROBLEM/CONDITION: In the United States, approximately 600,000 hysterectomies are
      performed each year, and the procedure is the second most frequently performed
      major surgical procedure among reproductive-aged women. REPORTING PERIOD COVERED:
      1980-1993. DESCRIPTION OF SYSTEM: This surveillance system uses data obtained
      from CDC's National Hospital Discharge Survey (NHDS) to describe the epidemiology
      of hysterectomy. The NHDS is an annual probability sample of discharges from non
      Federal, short-stay hospitals in the United States. RESULTS: In the United States
      during 1980-1993, an estimated 8.6 million women aged > or =15 years had a
      hysterectomy. The overall rate of hysterectomy declined slightly from 1980 (7.1
      hysterectomies per 1,000 women) to 1987 (6.6 per 1,000 women). The redesign of
      the NHDS in 1988 resulted in a decrease in estimated rates (i.e., the average
      annual rate for 1988-1993 was 5.5 per 1,000 women). Rates differed by age, with
      women aged 40-44 years most likely to have this procedure. Overall annual rates
      of hysterectomy did not differ significantly by race. The diagnosis most often
      associated with hysterectomy was uterine leiomyoma; during 1988-1993, this
      diagnosis accounted for 62% of hysterectomies among black women, 29% among white
      women, and 45% among women of other races. During 1988-1993, the percentage of
      hysterectomies performed by the vaginal route increased significantly;
      furthermore, an increasingly higher percentage of vaginal hysterectomies were
      accompanied by bilateral oophorectomy. From 1991 through 1993, laparoscopy was
      associated more frequently with vaginal hysterectomy than in previous years.
      INTERPRETATION: The rate of hysterectomy decreased slightly during the first half
      of the 14-year surveillance period, then leveled off during the second half. The
      increase in simultaneous coding of laparoscopy and vaginal hysterectomy on
      hospital discharge forms probably reflected the growing use of laparoscopically
      assisted vaginal hysterectomy. ACTIONS TAKEN: Continued surveillance for
      hysterectomy will enable changes in clinical practice (e.g., the use of LAVH) to
      be identified, and information derived from the surveillance system may assist in
      directing biomedical assessment priorities (e.g., to determine the reasons for
      race-specific differences in the prevalence of uterine leiomyoma).

PMID- 9259216
TI  - Abortion surveillance--United States, 1993 and 1994.
AB  - CONDITION: From 1991 through 1994, the number of legal induced abortions reported
      to CDC declined each year by < or =5% from the number reported for the preceding
      year. REPORTING PERIOD COVERED: This report summarizes and reviews information
      reported to CDC regarding legal induced abortions obtained in the United States
      during 1993 and 1994. This analysis also includes recently reported abortion
      related deaths that occurred during 1991. DESCRIPTION OF SYSTEM: For each year
      since 1969, CDC has compiled abortion data received from 52 reporting areas: 50
      states, the District of Columbia, and New York City. RESULTS: In 1993, 1,330,414
      legal abortions were reported to CDC, representing a 2.1% decrease from the
      number reported for 1992; in 1994, 1,267,415 abortions were reported,
      representing a 4.7% decrease from the number for 1993. In 1993 and 1994, the
      abortion ratio was 334 and 321 legal induced abortions per 1,000 live births,
      respectively. In 1993, the abortion rate was 22 per 1,000 women aged 15-44 years;
      in 1994, this rate declined to 21 per 1,000 women. Women who were undergoing an
      abortion were more likely to be young, white, and unmarried; most were obtaining
      an abortion for the first time. More than half of all abortions (52%-54%) were
      performed at < or =8 weeks of gestation, and approximately 88% were before 13
      weeks. Approximately 15%-16% of abortions were performed at < or =6 weeks of
      gestation, 16% were performed at 7 weeks, and 22% at 8 weeks. Younger women
      (i.e., women aged < or =19 years) were more likely to obtain abortions later in
      pregnancy than were older women. In 1991, 12 women died as a result of induced
      abortion: 11 of these deaths were related to legal abortion and one to illegal
      abortion. During 1991, the case-fatality rate of legal induced abortion was 0.8
      abortion-related deaths per 100,000 legal induced abortions. INTERPRETATION:
      Since 1990, the number of abortions has declined each year. Since 1987, the
      abortion-to-live-birth ratio also has declined; in 1994, it was the lowest
      recorded since 1977. This decrease in the abortion ratio reflected the lower
      proportion of pregnant women who obtained an induced abortion. As in previous
      years, deaths related to legal induced abortions occurred rarely (i.e.,
      approximately one death per 100,000 legal induced abortions). ACTIONS TAKEN: The
      number and characteristics of women who obtain abortions in the United States
      should continue to be monitored so that trends in induced abortion can be
      assessed, efforts to prevent unintended pregnancy can be evaluated, and the
      preventable causes of morbidity and mortality associated with abortions can be
      identified and reduced.

PMID- 9259217
TI  - Suicide by jumping.
AB  - This review summarizes the published literature on suicide by jumping, in
      particular focusing on the social and psychological characteristics of people who
      have chosen this method of suicide, and the opportunities for prevention. Suicide
      by jumping accounts for 5% of suicides in England and Wales, and there are marked
      variations in the use of this method world-wide. A number of locations have
      gained notoriety as popular places from which to jump. Such sites include The
      Golden Gate Bridge and Niagara Falls in the USA, and Beachy Head and the Clifton
      Suspension Bridge in the UK. There is no consistent evidence that those who
      commit suicide by jumping differ sociodemographically or in their psychopathology
      from those who use other methods of suicide, although this method is more often
      used for in-patient suicides, possibly due to lack of access to other means.
      Survivors of suicidal jumps experience higher subsequent rates of suicide and
      mental ill health, but the majority do not go on to kill themselves, suggesting
      that preventive efforts may be worthwhile. This view is supported by other
      evidence that restricting access to the means of suicide may prevent some would
      be suicides. Such measures may also reduce the emotional trauma suffered by those
      who witness these acts. Health authorities and coroners should consider reviewing
      local patterns of suicide by jumping, and if necessary institute preventive
      measures.

PMID- 9259218
TI  - Ten-year time trends of psychopathology in Dutch children and adolescents: no
      evidence for strong trends.
AB  - The 10-year time trends in competencies and problem scores in children and
      adolescents were assessed. Children and adolescents randomly selected from the
      Dutch general population in 1983 were assessed with the Child Behavior Checklist
      and the Teacher's Report Form. Their problem scores and competence scores were
      compared with those obtained by the same method 10 years later. No significant
      differences were found between the 1983 and 1993 total problem scores obtained
      from parents or teachers. On the level of problem items and scales, a few
      differences indicating an increase in problems were found. However, the magnitude
      of these differences was very small. Our results did not provide evidence for a
      clear secular increase in malfunctioning of Dutch children and adolescents.

PMID- 9259219
TI  - Group therapy for somatization disorders in general practice: effectiveness of a
      short cognitive-behavioural treatment model.
AB  - The objective of this study was to evaluate the effect of a short cognitive
      behavioural group therapy programme for somatization disorder in primary care.
      The treatment model was focused on patient education and stress relaxation. A
      controlled and prospective study design was used with repeated assessments of the
      patients' perception of their psychosocial problems, psychological distress and
      medication usage. The results were analysed up to 6 months after treatment and
      showed the treated patients to be moderately but significantly improved with
      respect to physical illness and somatic preoccupation, hypochondriasis, and
      medication usage. In a control group of untreated patients no such improvements
      were observed. In summary, the short group treatment programme used in this study
      may be beneficial for patients with somatization disorders. With some
      modifications it might be useful to practitioners in primary care for the
      management of psychosomatic disorders.

PMID- 9259220
TI  - Hopelessness and first-episode psychosis: a longitudinal study.
AB  - Hopelessness has not been adequately studied in first-episode psychotic patients,
      although it is already present at the early stages, especially in schizophrenic
      patients. We have studied 96 neuroleptic-naive psychotic patients (49
      schizophrenic patients and 47 other non-affective psychotic patients) over a
      period of 12 months after their first admission. The total score on the
      Hopelessness Scale (HS) at first admission was higher in the schizophrenic
      patients, and correlated with younger age and with negative symptoms. High HS
      scores at baseline predicted poor short-term outcome in schizophrenic patients,
      as evidenced by worse global functioning at the 12-month follow-up. These
      correlations were not observed in the other psychoses group. Our results suggest
      that young, severely affected schizophrenic patients who experience hopelessness
      might be at higher risk of poor outcome.

PMID- 9259221
TI  - Prevalence, recognition and management of mental disorders in primary health care
      in Northern Jordan.
AB  - This study examined the prevalence of psychiatric disorders and assessed factors
      that are assumed to be related to recognition of this morbidity among clinical
      patients. A total of 794 patients aged 18 years or older participated in the
      study. Using an Arabic-translated version of the General Health Questionnaire
      (GHQ-28), the prevalence of psychiatric morbidity was found to be 61%. The
      highest prevalence rates of psychiatric disorders were found in the 40 years and
      older age group, in female subjects, in uneducated and highly educated groups, in
      unemployed individuals, and in patients who were perceived to have 'fair' or
      'poor' physical health. Multiple logistic regression analysis revealed that
      unemployment and perceived severity of physical illness were positively
      correlated with psychiatric disorders, but no significant correlation was found
      with sex, age or level of education. The physicians in the present study were
      able to detect morbidity in only 24% of the patients. Among patients with
      psychiatric disorders, recognition of this morbidity was significantly greater in
      women, in patients who had consulted with their family doctors, in patients
      previously known to their physicians, and in patients with mild physical illness
      than in their counterparts. The most common lines of psychiatric management used
      in this study were referral to psychiatrists (47%) and psychotropic medication
      (16%).

PMID- 9259222
TI  - Serotonergic function in mothers of opioid addicts: correlation with comorbid
      depression.
AB  - The serotonergic (5-HT) function of 36 mothers of heroin addicts, of whom 16
      subjects were without psychopathological features (group A) and 20 subjects had
      major depressive disorders (group B), as well as 10 age- and sex-matched healthy
      controls, was examined by L-D-fenfluramine stimulation of secretion of prolactin
      (PRL) and cortisol. The subjects' addict relatives were also tested for
      personality features and hormonal responses to L-D-fenfluramine. The PRL and
      cortisol responses to the stimulus were normal in mothers of group A, and blunted
      in mothers of group B. A high frequency (70%) of heroin addicts with comorbid
      depression was found among the sons of group B mothers. The sons of depressed
      mothers showed reduced PRL and cortisol responses to fenfluramine. A significant
      direct correlation has been demonstrated between the PRL areas under curves (AUC)
      of mothers and sons in response to the 5-HT agonist. Our data suggest that
      genetic 5-HT impairment is not involved in the pathogenesis of heroin addiction
      or codependence per se, and is probably linked to the presence of familial
      depression in comorbidity with the addictive disorder.

PMID- 9259223
TI  - Psychosocial intervention following suicide attempt: a systematic review of
      treatment interventions.
AB  - Repeated suicide attempts are a common problem. However, few randomized
      controlled studies on the treatment of suicide attempters have been described.
      Although some of these studies showed beneficial effects on measures of well
      being, none of them demonstrated lasting positive effects on repeated suicidal
      behaviour. In an attempt to analyse the results obtained, a systematic review of
      randomized controlled trials of interventions for suicide attempters is
      presented. The literature was gathered by means of a CD-ROM literature reference
      search (MEDLINE/PSYCLIT). Subsequently, information on study design and treatment
      efficacy was abstracted. Studies that were homogeneous with regard to therapeutic
      principles were reviewed accordingly, and pooled analyses were performed. Meta
      analyses accounted for inter-study variance (random-effects model) to estimate a
      common-effect measure (relative risk). Systematic review of the data showed
      considerable differences in both study design and therapeutic protocols. In view
      of these differences, a single pooled analysis of all studies appeared to be
      unfeasible. A pooled analysis of studies that focus on psychiatric management of
      poor compliance showed no significant effect on the repetition of suicide
      attempts. Similarly, studies of psychosocial crisis intervention, as well as
      studies of guaranteed in-patient shelter in cases of emergency, did not show a
      significant reduction in repeated suicide attempts. However, the pooled results
      of four studies on cognitive-behavioural therapies showed a significant
      preventive effect on repeated suicide attempts. At present, only the cognitive
      behavioural approach appears to have a beneficial effect on repeated suicide
      attempts. However, because of methodological variability, the results obtained
      may be too optimistic. Additional research is required to establish the merits of
      this type of intervention.

PMID- 9259225
TI  - The recollection of parental rearing styles in patients with panic disorder.
AB  - Studies of the mental image of parents assessed by means of the Parental Bonding
      Instrument (PBI) in patients with panic disorder (according to DSM-III-R) have
      shown conflicting results. We examined 45 patients with panic disorder with and
      without agoraphobia and 116 controls using the PBI. As a group, patients with
      panic disorder reported significantly less care and more protection from parents
      than the controls. This difference was shown by the patients who had panic
      disorder with major agoraphobia, while those with minor agoraphobia did not
      differ from the controls. The present study supports the findings that low levels
      of care and high levels of protection, rather than affectionate constraint, were
      the predominant mental image reported by patients with panic disorder, using the
      PBI.

PMID- 9259224
TI  - Psychopathological and SPECT findings in never-treated schizophrenia.
AB  - A total of 24 never-treated (i.e. drug-naive) actively psychotic schizophrenic
      patients, operationalized according to DSM-III-R, were examined in a pre-post
      treatment design using the Positive and Negative Syndrome Scale for Schizophrenia
      (PANSS) and 99mTc-HMPAO-single photon emission computed tomography (SPECT) to
      assess regional cerebral blood flow (rCBF). The control subjects were 20 patients
      free of neurological and psychiatric symptoms. Before treatment there was only a
      slight hypofrontality, and hypoperfusion was observed in the left temporal
      superior region. After treatment, hypofrontality was reduced to one region and
      temporal hypoperfusion disappeared. Formal thought disorders were accompanied by
      increased rCBF in the bilateral frontal interior and left temporal superior
      regions. Delusions were associated with hypoperfusion in the anterior cingulate
      cortex. Negative symptoms showed no linkage to hypofrontality, either before or
      after treatment. Factor analysis showed delusions and hallucinations loading on
      different dimensions. The disorganized dimension correlated positively with all
      regions of interest, whereas these were negatively correlated with reality
      distortion.

PMID- 9259226
TI  - Low body weight in male children and adolescents with schizoid personality
      disorder or Asperger's disorder.
AB  - This study explored the hypothesis that body weight is reduced in male children
      and adolescents with schizoid personality disorder or Asperger's disorder. The
      body weights of 33 consecutively admitted male subjects with one of these
      disorders were retrospectively assessed with percentiles for the body mass index
      (BMI). The mean percentile (+/- SD) for the BMI was 31.6 +/- 27.6 and differed
      significantly from the expected value of 50 (P<0.001). Ten subjects had a BMI of
      < or = 10th age percentile. Post hoc comparisons revealed that BMI percentiles
      were (a) reduced to a similar extent in patients with schizoid personality
      disorder and Asperger's disorder and (b) reduced to a greater extent in patients
      with abnormal eating behaviour. During childhood and adolescence both diagnoses
      are associated with an increased risk of being underweight. Population-based BMI
      percentiles are useful for detecting associations between specific
      psychopathological syndromes and body weight.

PMID- 9259228
TI  - Illumination perception in photophobic patients suffering from panic disorder
      with agoraphobia.
AB  - Ten (6.9%) of a sample of 144 patients with panic disorder and agoraphobia
      developed photophobic behaviour in the course of their anxiety disorder. Their
      illumination ratings were characterized before and after cognitive behaviour
      therapy and compared to 10 age- and sex-matched normal control subjects. The
      illumination of a sheet of printed paper by a continuously adjustable reading
      lamp was rated by the subjects as 'too dark', 'comfortable' or 'too bright'. The
      ratings for comfortable luminance were significantly lower in the photophobic
      patients than in the controls, and renormalized after cognitive behavioural
      therapy. No differences were observed in the ratings for 'too dark' and 'too
      bright'. Photophobia in a subsample of patients with panic disorder is a state
      dependent phenomenon that can be influenced by cognitive behavioural therapy. The
      role of neurotransmitters, conditioning processes and a concomitant neurasthenic
      syndrome requires further characterization.

PMID- 9259227
TI  - Suicides among physicians, engineers and teachers: the prevalence of reported
      depression, admissions to hospital and contributory causes of death.
AB  - The number of admissions to hospital, reported diagnoses, prevalence of reported
      depression and contributory causes of death among Finnish physicians, engineers
      and teachers who committed completed suicide between 1986 and 1993 were studied.
      The data for hospital admissions with diagnoses were obtained from the Finnish
      Hospital Discharge Register. Thin-layer chromatography was used to detect drugs
      in the liver, a dual-column gas chromatographic method was used for screening and
      quantification of drugs in the blood sample, and a head-space chromatographic
      method was used to measure blood alcohol levels. Physicians had more somatic
      diagnoses than the reference groups, and the prevalence of reported depression
      was higher among females than males. A minority of the depressed subjects had
      been admitted to hospital, although depression was observed to be the most
      prevalent contributory cause of death in all of the groups studied. The
      physicians used solid or liquid substances, especially barbiturates, as the main
      method of suicide. It is possible that depression in physicians, especially in
      male subjects, is undertreated in psychiatric hospitals.

PMID- 9259229
TI  - Parent, teacher and self-reports as predictors of signs of disturbance in
      adolescents: whose information carries the most weight?
AB  - We evaluated the ability of parents, teachers and self-reports to predict signs
      of maladjustment in 353 11- to 14-year-olds from the general population, over a 4
      year time interval. Odds ratios were computed in order to test the ability of
      problem scales to predict later mental health referral and measures of parents'
      and children's own perceptions of the existence of major problems. Each informant
      made its own unique and indispensable contribution to the prediction of signs of
      maladjustment. Although teachers are often perceived as less able to assess
      internalizing problems than mothers and the children themselves, the present
      study showed that teachers' evaluations of internalizing problems are highly
      relevant if we take their ability to predict the subject's own perceptions of
      having problems as the criterion.

PMID- 9259230
TI  - Successful use of a selective serotonin reuptake inhibitor in a patient with
      multiple chemical sensitivities.
AB  - A 53-year-old man with multiple chemical sensitivities (MCS) received the
      selective serotonin reuptake inhibitor (SSRI) citalopram for treatment of
      depression. The treatment was successful and, in parallel to the remission of the
      depressive symptoms, all MCS symptoms vanished. This suggests that a subgroup of
      MCS patients may have an atypical depression, that they should be psychiatrically
      evaluated, and that antidepressive pharmacological treatment may be considered in
      cases of MCS.

PMID- 9259231
TI  - Stretch-activated nonselective cation, Cl- and K+ channels in apical membrane of
      epithelial cells of Reissner's membrane.
AB  - Ion channels on the apical membrane of epithelial cells (the surface facing the
      endolymph) of acutely isolated Reissner's membrane from guinea-pig cochlea were
      investigated by using patch-clamp technique in cell-attached and inside-out
      configurations. Three types of ion channel were identified: namely, a stretch
      activated nonselective cation, a chloride and a potassium channel. When the
      pipette was filled with high-K+ endolymph-like solution, the most significant
      channel activity was nonselective cation channels (85/110, 77% patches). The
      current versus voltage relationship was linear with a unitary conductance of 22.1
      +/- 0.4 pS and reversal potential (Vr) of 2.3 +/- 0.8 mV (n = 18). The channel
      exhibited a lower conductance (14.0 +/- 0.6 pS, n = 8) to Ca2+. The open
      probability was low (NPo approximately 0.1) in cell-attached configuration under
      +60 mV pipette potential and increased when the membrane was stretched with
      negative pressure. The channel was blocked by 10 microM extracellular Gd3+. The
      two other types of channels were a small voltage-sensitive Cl- channel (6.0 +/-
      0.3 pS; 91/99, 92% patches) and a K+ channel (approximately 30 pS; 29/191, 15%
      patches). These channels might play roles in the regulation of cell volume, in
      balancing the hydrostatic pressure across Reissner's membrane and in maintaining
      the electrochemical composition of endolymph.

PMID- 9259232
TI  - Electrophysiology and pharmacology of outward potassium currents in semicircular
      canal hair cells of toadfish, Opsanus tau.
AB  - Outward currents from hair cells from the horizontal semicircular canal (HSCC) of
      the toadfish were investigated using whole cell patch clamp methods. Two classes
      of hair cells are found. One class (approx. 10% of cells) showed only a non
      inactivating current (IKCa) which was blocked by 2 mM TEA. A second class had
      both inactivating and non-inactivating currents. The former (IA) was blocked by 4
      AP (1 mM) and the latter (IKCa) by TEA (2-20 mM) . While the majority of the
      cells expressed both these outward currents, due to IA inactivation both currents
      are functionally present in the same cell only between -60 and -40 mV. At more
      depolarized membrane potentials, IA was inactivated, suggesting that a single
      hair cell may have two distinct signalling modes, one dominated by IA at more
      hyperpolarized membrane potentials and the other by IKCa at depolarized values
      where ICa is beginning to grow, increasing both amplitude and activation rate of
      IKCa. The switch between modes will be determined by the amplitude and frequency
      characteristics of the stimulus and possibly also by actions of efferent
      transmitters. In current clamp mode, 10% of the HSCC hair cells showed high Q and
      high frequency resonance, from 44 to 360 Hz at 12 degrees C. These cells
      expressed only one outward calcium dependent, non-inactivating, TEA sensitive
      current, characteristic of IKCa. A suggested role for high frequency resonance is
      as positive feedback to produce a high frequency updating of the stereociliary
      compliance to most faithfully transduce angular acceleration.

PMID- 9259233
TI  - Interactions between pulse separation and pulse polarity order in cochlear
      implants.
AB  - Interactions between pulse separation and pulse polarity order were examined
      using psychophysical studies of electrical detection thresholds in nonhuman
      primates. Subjects were trained using acoustic stimuli, then deafened in one ear
      and implanted with an electrode array for electrical stimulation of the cochlea.
      Threshold vs pulse separation functions for trains of biphasic electrical pulses
      were compared for constant and alternating leading phase polarity. When leading
      phase polarity was held constant, threshold vs pulse separation functions were
      nonmonotonic (U-shaped). Small polarity-dependent (cathodic vs anodic leading
      phase) differences in absolute thresholds were observed at long pulse
      separations, but function shape was independent of leading phase. When leading
      phase polarity alternated, there was a pronounced reduction in thresholds at
      short pulse separations (below about 1 ms), resulting in monotonically increasing
      threshold vs pulse separation functions. At long pulse separations, functions for
      alternating and constant polarity stimuli were similar. Polarity effects were
      most apparent for longer duration trains (20 pulses) at long pulse durations (1-2
      ms/phase). For stimuli consisting of only two biphasic pulses, alternating
      polarity effects depended on whether cathodic or anodic phases were adjacent. The
      neural mechanisms underlying these effects probably include refractory properties
      and/or residual potentials.

PMID- 9259234
TI  - Processing and analyzing the mouse temporal bone to identify gross, cellular and
      subcellular pathology.
AB  - A technique has been developed for preparing the mouse temporal bone for
      histopathological examination: first, as a whole mount to detect any gross
      malformations of the bony or membranous labyrinths; second, in dissected segments
      to localize damage in the different sensory organs and to quantify sensory- and
      supporting-cell losses; and finally, in semi-thick and thin sections to identify
      and characterize subcellular pathology. Examples are given of the successful
      application of this technique to mice with very different inner-ear problems,
      including those with an abnormally short cochlear spiral, a defective lateral
      semicircular canal, abnormal otoliths over the saccular macula, an increased
      susceptibility to noise damage and those which lack fibroblast growth factor
      receptor 3.

PMID- 9259235
TI  - Acute sensitivity to interaural time differences in the inferior colliculus of a
      bat that relies on passive sound localization.
AB  - Gleaning bats rely on passive hearing to detect and localize terrestrial prey,
      and display remarkable accuracy in their passive sound localization. This study
      examines binaural processing in the inferior colliculus (IC) of the pallid bat
      (Antrozous pallidus), a gleaner that attends to prey-generated noise transients
      to locate prey. The primary focus is to determine whether neurons in its lateral
      IC, a region that appears dedicated to passive localization, possess a level of
      sensitivity to interaural time difference (ITD) sensitivity sufficient to
      indicate the use of ITDs in sound localization. Such a sensitivity was suspected
      because the pallid bat is capable of very accurate passive sound localization at
      the lower end of its audible range, where interaural intensity differences (IIDs)
      are small and may not provide sufficient spatial information. Because the pallid
      bat's audible range is too high for neurons to phase-lock to carrier frequencies,
      neurons were tested with square-wave, amplitude-modulated tones and noise to
      determine their sensitivity to ITDs in the sound envelope. Their sensitivity to
      the bat's behaviorally relevant ITD range of +/- 70 micros, and their low average
      interaural time/ intensity trading ratios (18 micros/dB) suggest that the pallid
      bat IC may have the greatest ITD sensitivity reported in a high-frequency
      mammalian auditory system.

PMID- 9259236
TI  - Expression of cytochrome oxidase in hair cells of the teleost utricle.
AB  - Ultrastructural variation in some cytoplasmic organelles and synaptic structures
      is one characteristic distinguishing the types of hair cells in the teleost ear.
      In this study, we explored differences in mitochondria by analyzing mitochondrial
      reactivity for cytochrome oxidase (COX) in hair cells of the teleost utricle. The
      reactivity for COX within mitochondria in the subcuticular compartment directly
      beneath the cuticular plate differentiated among hair cells in utricles of three
      teleost species, Carassius auratus, Pantodon buchholzi, and Astronotus ocellatus.
      Mitochondria in the subcuticular region of hair cells in the striola reacted
      intensely. Within juxtastriola and extrastriolar hair cells near the striola,
      mitochondria reacted at a lowered intensity than in striolar hair cells.
      Subcuticular mitochondria of extrastriolar hair cells located distant from the
      striola reacted negligibly. The reactivity of mitochondria in other cytoplasmic
      compartments did not provide similar evidence for distinguishing among teleost
      hair cells. Mitochondria within intraepithelial branches of the eighth nerve
      terminals in the different utricular regions reacted to COX histochemistry
      commensurate with their respective presynaptic hair cells. Branches of sensory
      afferent neurons innervating striolar hair cells displayed a dense COX reaction.
      Sensory afferents innervating the extrastriolar hair cells did not display many
      mitochondria at synapses nor, when present, was the staining as dense. The
      presynaptic side of the hair cell-afferent nerve synapse usually, but not always,
      contained reactive mitochondria. The presynaptic side of the efferent nerve-hair
      cell synapse did not necessarily contain mitochondria. Mitochondria filling the
      cytoplasm in a type of juxtamacula cell revealed uniformly dense COX reactivity.

PMID- 9259237
TI  - Suppression of otoacoustic emission is unchanged after several minutes of
      contralateral acoustic stimulation.
AB  - The influence of variable durations of contralateral acoustic stimulation on the
      suppression of click-evoked otoacoustic emissions was investigated in order to
      determine whether olivocochlear efferent fibers are equally effective whatever
      the acoustical stimulation duration or if they show fatigue. The suppression
      effect was measured for contralateral stimulus durations ranging from 10 to 180 s
      prior to the onset of otoacoustic emission recording, and continuing throughout
      the recording time (60 s). No significant stimulus duration effect was found.

PMID- 9259238
TI  - Immunoglobulin deposition in thickened basement membranes of aging strial
      capillaries.
AB  - The presence of immunoglobulins in the thickened basement membrane (BM) of aging
      strial capillaries was investigated as a possible indicator of autoimmunity in
      the genesis of atypical BM. Cochleas from young and old Mongolian gerbils raised
      in quiet were examined by immunostaining at the light microscopic level for IgG
      and IgM and for the BM components laminin (La) and type IV collagen (IV-C).
      Another age-graded series of cochleas was stained for IgG at the ultrastructural
      level. No immunoreactive IgG was detected in specimens from animals less than 6
      months old. In contrast, 2 of 12 cochleas from 20- to 28-month-old gerbils and 11
      of 20 cochleas from gerbils 30 months or older showed positive staining for IgG
      in strial capillary BM. IgM was not detected at any age. At the electron
      microscope level, no immunoreactive IgG was detected in the stria of cochleas
      younger than 30 months. However, labeling demonstrative of IgG was observed in
      the thickened BM of some strial capillaries in all six cochleas from gerbils
      older than 33 months. Lysosome-like granules in endothelial cells and the
      superiormost marginal cells also stained for content of IgG as did fibrillar
      material in edematous regions in the intrastrial space. In addition to showing
      accumulation of IgG, the findings confirm our prior demonstration of increased La
      deposition in the thickened strial capillary BM of all cochleas from old gerbils.
      The BM alterations appear confined to strial capillaries in old gerbils, since
      morphological observations and immunostaining for La and IgG failed to detect
      changes in BMs at any other site in a wide survey of aged gerbil organs including
      vessels in other regions of the affected cochleas. The results point more towards
      the development of an age-dependent permeability to IgG selectively in strial
      capillaries than to autoimmunity as an explanation of the IgG in BM.

PMID- 9259239
TI  - Immunohistochemical localization of keratan sulfate in the chinchilla inner ear.
AB  - Keratan sulfate (KS) was immunolocalized in the chinchilla cochlea and vestibular
      system using indirect immunohistochemistry and a monoclonal antibody (clone 5-D
      4) directed against a proteoglycan core antigen. As a positive control, anti-KS
      Mab reactivity was found in the pericellular matrix and lacuna walls of temporal
      bone osteocytes. In the cochlea, anti-KS Mab reactivity was abundant in the basal
      cell layer of the stria vascularis and in the marginal band and Hensen's stripe
      of the tectorial membrane. Less anti-KS Mab reactivity was present in the cover
      net, Hardesty's membrane and the upper fibrous zone of the limbal layer of the
      tectorial membrane. In the vestibular system, anti-KS Mab reactivity was
      immunolocalized to a portion of the epithelium overlying the cupula of the crista
      ampullaris, in the apical surface of crista ampullaris epithelium, crista
      ampullaris stereocilia and in the otoconia. Elucidating the distribution of KS in
      the cochlea will improve our understanding of cochlear anatomy and is a first
      step toward understanding the etiology of hearing loss observed in diseases
      involving KS metabolism, namely, mucopolysaccharidosis type IV (Morquio's
      syndrome).

PMID- 9259240
TI  - Inhibition sensitive to interaural time difference in the barn owl's inferior
      colliculus.
AB  - In spontaneously active neurons in the external nucleus of the inferior
      colliculus of the barn owl, a stimulus-driven discharge was followed by a
      quiescent period lasting tens of milliseconds before the spontaneous activity
      resumed. The more favorable the interaural time difference, the longer the quiet
      period. The duration of the quiescent period also depended on stimulus frequency.
      Frequencies different from the neuron's best frequency induced shorter quiescent
      periods, although they could elicit similar rates of impulses. Also, the duration
      of the quiescent period was independent of interaural intensity difference. Thus,
      the quiet period is not due to an after-hyperpolarization but was an inhibitory
      effect that depended on the activity of other neurons. In some neurons, discharge
      continued after the stimulus without a quiescent period and gradually decayed
      over a period of 50-100 ms past the stimulus offset. The similarity between the
      quiescent period of the neurons mentioned above and the time course of the
      poststimulus discharge in these neurons suggests that these neurons serve as
      inhibitory interneurons.

PMID- 9259241
TI  - The structure of the statocyst of the freshwater snail Biomphalaria glabrata
      (Pulmonata, Basommatophora).
AB  - The structure of the statocyst of the freshwater snail Biomphalaria glabrata has
      been examined by light and electron microscopy. The two statocysts are located on
      the dorsal-lateral side of the left and right pedal ganglion. The statocysts are
      spherical, fluid-filled capsules with a diameter of approximately 60 microm for
      young and 110 microm for adult snails. The wall of the cyst is composed of large
      receptor cells and many smaller supporting cells. The receptor cells bear cilia
      which are evenly distributed on the apical surface. The cilia have the typical
      9+2 internal tubule configuration. Striate rootlets originate from the base of
      the basal body and run downward into the cytoplasm. Side-roots arise from one
      side of the basal body and a basal foot from the other. For each receptor cell,
      the basal foot always points to the periphery of the surface, indicating that the
      receptor cell is non-polarized. The receptor cells contain cytoplasmic organelles
      such as mitochondria, ribosomes, rough and smooth endoplasmic reticulum, compact
      Golgi bodies and multivesicular bodies. Supporting cells bearing microvilli are
      interposed between the receptor cells. The junction complex between the
      supporting cells and the receptor cells is composed of adherens and septate
      junctions, while between supporting cells only the adherens junctions are
      present. The static nerve arises from the lateral side of the cyst and contains
      axons in which parallel neurotubules and mitochondria are found. The axons arise
      directly from the base of the receptor cells without synapse. In the cyst lumen
      there are unattached statoconia. The statoconia have a plate-like or concentric
      membranous ring structure. Based on the morphology, the function of the statocyst
      in Biomphalaria is discussed.

PMID- 9259242
TI  - Development of the statocyst in the freshwater snail Biomphalaria glabrata
      (Pulmonata, Basommatophora).
AB  - The development of the statocyst of the freshwater snail Biomphalaria glabrata
      has been examined from embryo to adult. Special emphasis was put on the growth of
      the statoconia in the statocysts. In the statocysts of embryonic snails (90-120 h
      after oviposition) there is not a single statolith but an average of 40-50
      statoconia per statocyst. The number of statoconia increases to 385-400 when the
      snails reach a shell diameter of 4 mm and remains relatively constant thereafter,
      irrespective of shell size. Small statoconia are found in supporting cells, which
      suggests that the statoconia are produced within these cells. The average
      diameter of statoconia and the total mass of statoconia increase with increasing
      shell diameter. The average number of large statoconia (diameter > 7 microm) per
      statocyst continues to increase from 2 to 10 mm animals while the number of small
      ones (diameter < 4 microm) initially rises and then decreases after 4 mm. These
      results demonstrate continuous growth of the statoconia in the cyst lumen of
      Biomphalaria. The single statoconia vibrate in a regular pattern in vivo,
      indicating beating of the statocyst cilia. The statoconia sink under the
      influence of gravity to load and stimulate receptor cells which are at the
      bottom. The length of cilia and the size of statocyst gradually increase as the
      animal grows. However, the increase in the volume of the statocyst is relatively
      small compared with the increase in body weight during normal development.

PMID- 9259243
TI  - Immunoreactivity for taurine in the cochlea: its abundance in supporting cells.
AB  - Taurine is the second most abundant free amino acid in the brain where its
      osmoregulatory function is well established. Taurine-deprived kittens show
      retinal pathology leading to blindness. In the inner ear, taurine has been
      reported to be the most abundant free amino acid although its role in inner ear
      function is not known. Immunohistochemistry was employed here to investigate the
      localisation of taurine in normal cochleae of the guinea pig compared with two
      different conditions: experimentally induced endolymphatic hydrops and after oral
      administration of glycerol. In normal cochleae, by light microscopy, taurine-like
      immunoreaction was never observed in the sensory outer hair cells and appeared
      absent from the inner hair cells. In contrast taurine-like immunolabeling was
      found to be present in all supporting tissue with the striking exception of the
      tectorial membrane and the outer pillar cell which had no or little taurine
      immunoreactivity respectively. In early experimental endolymphatic hydrops, the
      distribution of taurine-like immunoreactivity appeared similar to that observed
      for normal cochleae. In long-term hydrops, degenerated outer hair cells were
      replaced by the swelling of the phalangeal process of the Deiters' cells which
      became highly immunoreactive to taurine. After glycerol administration, the
      tectorial membrane became more tightly bound to the apical surface of the sensory
      hair cells and distinctly immunoreactive to taurine. The localisation of taurine
      in the organ of Corti shown here is consistent with taurine being involved in the
      maintenance of osmotic equilibrium in the normal and perhaps also in the
      restructuration of the pathological organ of Corti.

PMID- 9259244
TI  - Consensus and the T-score fallacy.

PMID- 9259245
TI  - A multidimensional intervention strategy to reduce hip fracture risk in the
      elderly: isn't it time to act?

PMID- 9259246
TI  - Prevention and treatment of postmenopausal osteoporosis. National Consensus of
      the "Belgian Bone Club", November 1996.

PMID- 9259247
TI  - Site-dependent bone mineral density response to oral pamidronate and calcium in
      postmenopausal osteoporosis: a preliminary report.
AB  - Radiologically diagnosed postmenopausal osteoporotic patients with at least one
      nontraumatic vertebral flattening were treated for one year with either oral
      pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone
      (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck,
      trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine
      the number of responders at each site. As no densitometric inclusion criteria
      were stipulated, wide inter- and intra-individual variations in both regional
      basal BMD and response to therapy were found. However, the APD-treated group
      showed significant mean BMD increases in spine (+3.1%; p < 0.001) and femoral
      neck (+3.2%; p < 0.002) versus basal level, whereas the calcium only group failed
      to exhibit significant differences. The entire 60-strong population was then
      split into two groups, according to whether individual BMD content was greater or
      less than the mean basal value for each skeletal site evaluated. For either
      treatment, subpopulations with lower basal BMD tended to achieve greater bone
      gain, though statistically significant differences were only disclosed at
      trochanter (p < 0.004) with APD and at femoral neck (p < 0.002) in the calcium
      only group. Globally speaking, increases in BMD were observed in 60-80% of
      patients receiving either treatment - who were thus defined as responders - at
      each particular skeletal area assessed. However, when only skeletal areas with
      low basal BMD were considered, the number of responders reached 60-100%.
      Responsive sites varied among patients: out of 56 cases, 9 (24%) on APD and 6
      (32%) on calcium alone responded in all 4 areas evaluated, while a single case on
      the latter treatment failed to show BMD response at any site. Overall, the mean
      number of responsive sites was 2.7. Odds ratios were calculated considering
      treatment modality and high or low basal BMD as parameters, but no significant
      differences were found in the number of responders. It may be concluded that APD
      induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal
      osteoporosis, whereas calcium alone leads to non significant variations, both
      findings being in agreement with reported data. Therefore, evaluated APD doses
      enhance mineralization in responsive sites alone, but fail to increase the total
      number of responders. Interestingly, responsive sites seem to be those relitively
      spared by the course of the disease.

PMID- 9259248
TI  - The effect of a modified etidronate cyclical regimen on postmenopausal
      osteoporosis: a four-year study.
AB  - To develop an improved treatment schedule for osteoporosis, a study was
      undertaken in 100 postmenopausal women using a modified ADFR 90-day cyclical
      regimen with etidronate. After one year of treatment, the etidronate-treated
      group showed a significant increase in bone density of the spine, which continued
      over the following 2 years of treatment and remained stable during the fourth
      year. In contrast, in the non-etidronate group, bone density decreased
      significantly after four years. In addition, the fracture rate was significantly
      lower in the etidronate group than in the non-etidronate group. Side effects were
      minimal in both groups and no serious adverse reactions were reported. In
      conclusion, it appears that a cyclical regimen using 1,25-dihydroxyvitamin D3,
      etidronate and calcium increases bone mass and reduces fractures with no
      significant side effects, thus making a useful contribution in the treatment of
      postmenopausal osteoporosis.

PMID- 9259249
TI  - Reflex sympathetic dystrophy syndrome with microtrabecular fracture in a patient
      with osteogenesis imperfecta.
AB  - A case of reflex sympathetic dystrophy syndrome (RSDS) in a patient with
      osteogenesis imperfecta (OI) is reported. We discuss the association of OI,
      manifested by microfractures of the trabecular bone due to marked bone fragility,
      and the appearance of RSDS. Magnetic resonance imaging (MRI) was helpful in
      assessing the presence and extent of the trabecular fractures.

PMID- 9259250
TI  - Histological appearance of the intra-osseous vessels of the femoral head in
      aseptic osteonecrosis of the hip, with or without antiphospholipid antibodies.
AB  - It has been suggested that in some patients non-traumatic aseptic osteonecrosis
      of the hip (AOH) could be the result of the intra-osseous thrombosis.
      Antiphospholipid antibodies (APL) have been associated with venous and arterial
      occlusive events and the association between AOH and APL syndrome has been
      reported. OBJECTIVES: To compare bone vessels of the femoral head in patients
      operated on for AOH with or without APL. PATIENTS: Twenty patients (mean age 47
      yrs) with AOH were included: in eight patients APL (IgG-ELISA) were negative (< 8
      GPL units), in nine patients APL were doubtful (8-15 GPL units), and in three
      patients APL were positive (> 15 GPL units). METHODS: Bone vessels were examined:
      arteriosclerotic lesions, i.e. fibrosis or thickening of the media and rupture of
      the internal elastic lamina, thrombosis or vasculitis were sought in the femoral
      heads after total hip replacement or core decompression. RESULTS: Bone vessel
      lesions were the same in the three groups.

PMID- 9259251
TI  - Bone scintigraphy equipped with a pinhole collimator for diagnosis of avascular
      necrosis of the femoral head.
AB  - The objective was to compare the sensitivities for diagnosis of avascular
      necrosis of the femoral head of bone scintigraphy equipped with a pinhole
      collimator and with an high resolution parallel collimator. Bone scintigraphy
      equipped with a pinhole collimator and with an high resolution parallel
      collimator were performed in 16 patients with bilateral (n=7) or unilateral (n=9)
      avascular necrosis of the femoral head. Bone scintigraphy equipped with a pinhole
      collimator documented a photopenic defect in 78.3% of the necrotic hips, while
      bone scintigraphy equipped with an high resolution parallel collimator documented
      a defect in 47.8%. There was no false-positive diagnosis of avascular necrosis of
      the femoral head on either bone scintigraphy equipped with a pinhole or with an
      high resolution parallel collimator. In conclusion, bone scintigraphy equipped
      with a pinhole collimator has a greater sensitivity for diagnosis of avascular
      necrosis of the femoral head than bone scintigraphy equipped with an high
      resolution parallel collimator.

PMID- 9259252
TI  - Clinical setting of patients with systemic sclerosis by serum autoantibodies.
AB  - Associations of antinuclear (ANA) and anticardiolipin (aCL) antibodies with
      clinical manifestations were analyzed in patients with systemic sclerosis (SSc).
      We studied 105 SSc patients: 28 had limited cutaneous SSc (lcSSc) involving
      fingers; 36 had intermediate cutaneous SSc involving limbs and face; 33 had
      diffuse cutaneous SSc (dcSSc) involving the trunk; 8 had a sclerosis sine
      scleroderma. Clinical manifestations and instrumental and laboratory findings
      were considered to calculate a disease score. Serum anticentromere (ACA), anti
      topoisomerase I (anti-topo I) antibodies, and aCL (of IgG/IgA/IgM classes) were
      investigated by conventional methods. ACA positive patients (n=18), compared to
      ACA negative, showed higher prevalence of IcSSc (p < 0.001), lower prevalence of
      restrictive ventilatory defect (p=0.006), and lower disease score (p=0.008). Anti
      topo I positive patients (n= 70) showed lower prevalence of lcSSc (p =0.001)
      compared to anti-topo I negative. In aCL positive patients (n=27) widespread skin
      and visceral involvement occurred more frequently than in aCL negative. The
      association with myocardial ischemia or necrosis (p=0.010) was significant.
      Occurrence of ACA excluded the coexistence of anti-topo I (p < 0.001), and aCL
      (p=0.037). aCL positive patients showed higher disease score in comparison with
      ACA positive patients (p=0.003). In conclusion ACA recognize patients with a mild
      disease. aCL in contrast to ACA are better than anti-topo I in recognizing the
      most severe pictures of SSc.

PMID- 9259253
TI  - A longitudinal study of pulmonary function in Danish patients with systemic
      sclerosis.
AB  - OBJECTIVE: To determine the types, prevalence and development of respiratory
      abnormalities in patients with systemic sclerosis (SSc), and to correlate the
      results with clinical and serological findings. METHODS: 176 patients with SSc
      observed longitudinally were retrospectively included in the study. The change
      per year of vital capacity (VC), forced expiratory volume in one second/vital
      capacity (FEV1/VC), diffusing capacity (DLco) and diffusing constant (Kco) of
      carbon monoxide from the first till the latest pulmonary function test were
      correlated to clinical and serological findings, including anti-centromere, anti
      Scl-70, and antinucleolar antibodies. RESULTS: An isolated reduction of DLco was
      seen in 47% and a restrictive ventilatory pattern in 25% of the patients.
      Restrictive ventilatory pattern correlated to pulmonary fibrosis, dyspnoea, a low
      prevalence (13%) of anti-centromere antibodies and a high prevalence of anti-Scl
      70 antibodies (36%). Progression of DLco reduction was related to long disease
      duration, presence of anti-centromere antibodies and absence of treatment with
      penicillamine. CONCLUSION: Pulmonary involvement is common in patients with SSc.
      The occurrence of different serological abnormalities in patients with
      restrictive disease and in patients with progressive isolated reduction of DLco,
      suggests that the two types of pulmonary damage may have different pathogeneses
      rather than being different stages in the progression of pulmonary damage.

PMID- 9259254
TI  - Use of complementary therapies by individuals with 'arthritis'.
AB  - The popularity of complementary medicine is at an all-time high. Rheumatological
      patients are amongst its most frequent users. This survey was aimed at generating
      insight into this phenomenon. A self-selected convenience sample of 3384
      individuals with 'arthritis' was sent a purpose-designed questionnaire. 1020
      completed questionnaires were received (response rate = 30.1%). One third of
      respondents had received at least one treatment from a complementary
      practitioner. Orthodox therapies were generally perceived as more effective than
      complementary treatments. Therapeutic encounters with complementary practitioners
      were viewed as markedly more satisfying than those with GPs. Adverse effects
      reported in connection with orthodox treatments were more frequent and severe
      than those reported with complementary therapies. No firm conclusions can be
      drawn from these data. However, a hypothesis emerges that complementary medicine
      is well accepted by rheumatological patients and perceived to have certain
      advantages over mainstream medicine.

PMID- 9259255
TI  - Ultrasound transmission velocity of the proximal phalanxes of the non-dominant
      hand in the study of osteoporosis.
AB  - The aim of our study was to evaluate a quantitative ultrasound technique for
      measuring bone tissue at the proximal phalanxes of the non-dominant hand. We
      correlated the mean value of the amplitude-dependent speed of sound (AD-SoS)
      measured at the distal metaphysis of the last four proximal phalanxes with age,
      months since menopause and bone mineral density (BMD) of the lumbar spine in 264
      women. We further assessed the ability of the AD-SoS to discriminate between
      normal and osteoporotic subjects with documented vertebral fractures. We found a
      positive correlation between the AD-SoS and the lumbar spine BMD, whereas the AD
      SoS negatively correlated with age and months since menopause. The AD-SoS showed
      a higher correlation with age changes and months since menopause than BMD. The AD
      SoS was significantly higher in healthy females than in osteoporotic ones (p <
      0.001). Multiple logistic regression analysis showed for age-adjusted values that
      AD-SoS decrease is significantly associated to the presence of fracture. Our
      results suggest that AD-SoS is valuable in assessing age and menopause related
      bone loss and is useful for diagnosing osteoporosis.

PMID- 9259256
TI  - Transient osteoporosis of the hip with joint effusion detected by
      ultrasonography.
AB  - Three cases of transient osteoporosis of the hip and their ultrasonographic
      findings are presented. Transient osteoporosis of the hip is an uncommon
      condition with pain in the hip area and limping. The diagnosis is supported by
      local radiological osteoporosis and other imaging methods. Exclusion of more
      common entities is required. Effusion of the hip joint detected by
      ultrasonography is also related to this condition, which must be taken into
      account in patients with hip pain.

PMID- 9259257
TI  - Sjogren's syndrome associated with autoimmune hepatitis. A case report.
AB  - Liver involvement in patients with primary Sjogren's syndrome is rare, usually
      without clinical significance and histologically characterized by a feature like
      stage 1 primary biliary cirrhosis. We describe herein a case of acute and severe
      autoimmune hepatitis in a patient suffering from primary Sjogren's syndrome. The
      diagnosis of Sjogren's syndrome was performed in 1989. In June 1995 the patient
      presented severe weakness, jaundice and elevation of transaminases; moreover IgG
      raised to 5560 mg/dl and ANA titre increased to 1:20480. The patient denied
      alcohol and drug use and a viral hepatitis was excluded. Antimitochondrial
      antibodies, anti-smooth muscle antibodies and antibodies against liver kidney
      microsomes were negative. An abdomen ultrasound examination revealed
      hepatomegaly, with irregular echogenic structure and lymphoadenomegaly near the
      celiac tripod. Liver biopsy demonstrated a picture of autoimmune hepatitis. The
      patient was treated with prednisone 50 mg/day and azathioprine 50 mg/day, with
      improvement in clinical and liver function indices. At present, the patient is
      given only 10 mg/day of prednisone. The association of Sjogren's syndrome with
      autoimmune hepatitis is very rare: in the literature only one other similar case
      has been reported.

PMID- 9259258
TI  - Neuroarthropathy of the shoulder of unexpected origin.
AB  - The authors describe the case of a 65-year-old woman who developed a sudden and
      painless palsy of right shoulder one month after a benign fall. Radiographs
      showed severe articular destruction. Neurologic examination revealed only a mild
      sensory loss of the right upper extremity. A diagnosis of syringomyelia was
      evoked and confirmed by spinal MRI. An upper extremity neuroarthropathy is
      usually caused by syringomyelia and is sometimes the first and leading symptom of
      this disease. Sensory neuropathy explains the incidence of this often painless
      osteoarthropathy. Treatment with bisphosphonate is discussed.

PMID- 9259259
TI  - A case of cytophagic histiocytic panniculitis: successful treatment of recurrent
      attacks with steroid pulse therapy and oral cyclosporin A.
AB  - We report a 35-year-old man, who had been diagnosed with Weber-Christian disease,
      presented with acute onset of high fever, malaise, jaundice and
      hepatosplenomegaly with subcutaneous nodules. Laboratory tests showed elevated
      serum ferritin and liver enzymes, especially lactate dehydrogenase (LDH), with
      pancytopenia and coagulation abnormalities. Peripheral blood and bone marrow
      examinations showed erythro-, leuko- and thrombo-phagocytic histiocytes and
      macrophages. The patient developed the same clinical features seven years ago.
      Based on diagnosis of cytophagic histiocytic panniculitis, the patient was
      treated with steroid pulse therapy and oral cyclosporin A. The combination
      therapy caused a marked improvement in the clinical condition.

PMID- 9259260
TI  - Systemic lupus erythematosus and amyloidosis.
AB  - Amyloidosis in association with Systemic Lupus Erythematosus (SLE) has rarely
      been reported. We report a patient with "SLE" and Amyloidosis presenting with
      recurrent bloody diarrhea and review the relevant literature.

PMID- 9259261
TI  - Pseudodystrophy at the lower limb in children.
AB  - The authors describe a 12-year old girl with a painful syndrome at the distal
      side of the left leg, resulting in limping, incapacity and severe muscle atrophy.
      Full investigation - no inflammatory laboratory signs, diffuse osteoporosis at
      the left leg, decreased bone mineral content at the same place, marked
      hypofixation on bone and vascular scintigraphy - suggested pseudodystrophy (5),
      which is often induced by psychological factors. Successful treatment was
      obtained by physiotherapy, hydrotherapy, slight doses of NSAID and psychological
      assistance. With regard to recent literature, the authors believe that reflex
      sympathetic dystrophy (RSD) in children is often over-diagnosed, since there are
      no recognised criteria for diagnosing RSD. Besides the clinical picture, changes
      on radiography (focal osteoporosis) and on scintigraphy (disturbed vascular
      scintigraphy with increased pooling in the initial phase and hyperfixation on
      bone scintigraphy) are necessary. When these are not available, pseudodystrophy
      is a more correct diagnosis.

PMID- 9259262
TI  - Isolated thrombocytopenia associated with low dose methotrexate therapy.

PMID- 9259263
TI  - Establishment and characterization of a human B cell line producing IgG type
      antibodies to DNA.

PMID- 9259264
TI  - Characterization of neo-centromeres in marker chromosomes lacking detectable
      alpha-satellite DNA.
AB  - Recent studies have implicated alpha-satellite DNA as an integral part of the
      centromere, important for the normal segregation of human chromosomes. To explore
      the relationship between the normal functioning centromere and alpha-satellite
      DNA, we have studied eight accessory marker chromosomes in which fluorescence in
      situ hybridization could detect neither pancentromeric nor chromosome-specific
      alpha-satellite DNA. These accessory marker chromosomes were present in the
      majority of or all cells analyzed and appeared mitotically stable, thereby
      indicating the presence of a functional centromere. FISH analysis with both
      chromosome-specific libraries and single-copy YACs, together with microsatellite
      DNA studies, allowed unequivocal identification of both the origin and structure
      of these chromosomes. All but one of the marker chromosomes were linear mirror
      image duplications, and they were present along with either two additional normal
      chromosomes or with one normal and one deleted chromosome. Indirect
      immunofluorescence analysis revealed that the centromere protein CENP-B was not
      present on these markers; however, both CENP-C and CENP-E were present at a
      position defining a 'neo-centromere'. These studies provide insight into a newly
      defined class of marker chromosomes that lack detectable alpha-satellite DNA. At
      least for such marker chromosomes, alpha-satellite DNA at levels detectable by
      FISH appears unnecessary for chromosome segregation or for the association of
      CENP-C and CENP-E at a functional centromere.

PMID- 9259265
TI  - The survival motor neuron protein in spinal muscular atrophy.
AB  - The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously
      expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations
      in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an
      autosomal recessive disorder that results in loss of motor neurons. SMN is found
      in the cytoplasm and nucleus. The nuclear form is located in structures termed
      gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein
      is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of
      fibroblasts from SMA patients with various clinical severities of SMA showed a
      moderate reduction in the amount of SMN protein, particularly in type I (most
      severe) patients. Immunocytochemical analysis of SMA patient fibroblasts
      indicates a significant reduction in the number of gems in type I SMA patients
      and a correlation of the number of gems with clinical severity. This correlation
      to phenotype using primary fibroblasts may serve as a useful diagnostic tool in
      an easily accessible tissue. SMN is expressed at high levels in brain, kidney and
      liver, moderate levels in skeletal and cardiac muscle, and low levels in
      fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately
      reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels
      in spinal cord from normals and non-SMA disease controls, but was reduced 100
      fold in spinal cord from type I patients. The marked reduction of SMN in type I
      SMA spinal cords is consistent with the features of this motor neuron disease. We
      suggest that disruption of SMN(T) in type I patients results in loss of SMN from
      motor neurons, resulting in the degeneration of these neurons.

PMID- 9259266
TI  - Genomic and mutational analysis of the mitochondrial trifunctional protein beta
      subunit (HADHB) gene in patients with trifunctional protein deficiency.
AB  - Mitochondrial trifunctional protein (TP), an enzyme of beta-oxidation, is a
      multienzyme complex composed of four molecules of the alpha-subunit (HADHA)
      containing the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains
      and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA
      thiolase domain. An inborn error of this enzyme complex can cause sudden infant
      death syndrome, acute hepatic encephalopathy or liver failure, skeletal myopathy,
      or hypertrophic cardiomyopathy. TP deficiency is classified into two different
      biochemical phenotypes: one represents the existence of both subunits and the
      lack of only the 3-hydroxyacyl-CoA dehydrogenase activity and the other
      represents the absence of both subunits and the lack of all three TP activities,
      although their clinical features are similar. We have identified two Japanese
      patients with this disorder. Three enzyme activities of TP were undetectable in
      fibroblasts from these two patients. We detected two mutations in the HADHB gene
      from two Japanese patients, an exonic single T insertion which created a new
      cryptic 5' splice site and a G1331A transition (R411 K). Patient 1 was a compound
      heterozygote, while patient 2 was a homozygote of a G1331A transition.

PMID- 9259267
TI  - Characterization of unconventional MYO6, the human homologue of the gene
      responsible for deafness in Snell's waltzer mice.
AB  - Deafness is the most common form of sensory impairment in humans. Mutations in
      unconventional myosins have been found to cause deafness in humans and mice. The
      mouse recessive deafness mutation, Snell's waltzer, contains an intragenic
      deletion in an unconventional myosin, myosin VI (locus designation, Myo6). The
      requirement for Myo6 for proper hearing in mice makes this gene an excellent
      candidate for a human deafness disorder. Here we report the cloning and
      characterization of the human unconventional myosin VI (locus designation, MYO6)
      cDNA. The MYO6 gene maps to human chromosome 6q13. The isolation of the human
      gene makes it now possible to determine if mutations in MYO6 contribute to the
      pathogenesis of deafness in the human population.

PMID- 9259268
TI  - Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric
      nephrolithiasis (kidney stones) disorders.
AB  - Mutations of the renal-specific chloride channel (CLCN5) gene, which is located
      on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney
      stones) in the Northern European and Japanese populations. CLCN5 encodes a 746
      amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and
      heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded
      outwardly rectifying chloride currents that were markedly reduced or abolished by
      these mutations. In order to assess further the structural and functional
      relationships of this recently cloned chloride channel, additional CLCN5
      mutations have been identified in five unrelated families with this disorder.
      Three of these mutations were missense (G57V, G512R and E527D), one was a
      nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two
      of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and
      the G57V and E527D mutations were identified in families of Afro-American and
      Indian origin, respectively. The G57V and 30:H insertion mutations represent the
      first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop
      mutation, which has been observed previously in an unrelated family, suggests
      that this codon may be particularly prone to mutations. Heterologous expression
      of the mutations resulted in a marked reduction or abolition of the chloride
      currents, thereby establishing their functional importance. These results help to
      elucidate further the structure-function relationships of this renal chloride
      channel.

PMID- 9259269
TI  - Autism and multiple exostoses associated with an X;8 translocation occurring
      within the GRPR gene and 3' to the SDC2 gene.
AB  - An X;8 translocation was identified in a 27-year-old female patient manifesting
      multiple exostoses and autism accompanied by mental retardation and epilepsy.
      Through molecular analysis using yeast artificial chromosomes (YACs) and cosmid
      clones, the translocation breakpoint was isolated and confirmed to be reciprocal
      within a 5'-GGCA-3' sequence found on both X and 8 chromosomes without gain or
      loss of a single nucleotide. The translocation breakpoint on the X chromosome
      occurred in the first intron of the gastrin-releasing peptide receptor (GRPR)
      gene and that on chromosome 8 occurred approximately 30 kb distal to the 3' end
      of the Syndecan-2 gene (SDC2), also known as human heparan sulfate proteoglycan
      or fibroglycan. The GRPR gene was shown to escape X-inactivation. A dosage effect
      of the GRPR and a position effect of the SDC2 gene may, however, contribute the
      phenotype observed in this patient since the orientation of these genes with
      respect to the translocation was incompatible with the formation of a fusion
      gene. Investigation of mutations in these two genes in unrelated patients with
      either autism or multiple exostoses as well as linkage and association studies is
      needed to validate them as candidate genes.

PMID- 9259270
TI  - Behaviour of a population of partially duplicated mitochondrial DNA molecules in
      cell culture: segregation, maintenance and recombination dependent upon nuclear
      background.
AB  - We have studied the dynamics of mitochondrial DNA maintenance and segregation in
      human cells using serial cybrid transfer of partially duplicated mitochondrial
      DNA, from a mitochondrial myopathy patient, to two distinct recipient cell types.
      The results indicate two radically different outcomes dependent upon nuclear
      background. In one case (lung carcinoma) there is systematic loss of the partial
      duplication by an implied recombinational mechanism. In another nuclear
      background (osteosarcoma) the duplicated molecules can survive, having only a
      marginal effect on mitochondrial respiratory function. Moreover, in the
      osteosarcoma nuclear background further disturbances of mtDNA maintenance
      frequently follow from cybrid transfer. These are progressive, catastrophic loss
      of mtDNA and further rearrangement to generate partially triplicated molecules.
      The results imply differential expression of nuclear genes regulating mtDNA copy
      number, replication and recombination in different human cell types.

PMID- 9259271
TI  - The Friedreich ataxia GAA triplet repeat: premutation and normal alleles.
AB  - The most common mutation causing Friedreich ataxia (FRDA), an autosomal recessive
      neurodegenerative disease, is the hyperexpansion of a polymorphic GAA triplet
      repeat localized within an Alu sequence (GAA-Alu) in the first intron of the
      frataxin (X25) gene. GAA-Alu belongs to the AluSx subfamily and contains several
      polymorphisms in strong linkage disequilibrium either with a subgroup of normal
      alleles, or with hyperexpanded FRDA-associated alleles. GAA repeat sizes in 300
      normal chromosomes (97 from carriers and 203 from controls) were distributed in
      two separate groups: 83% of them contained between six and 10 triplets (small
      normal alleles), while the remaining 17% had more than 12 triplets, up to 36
      (large normal alleles). Sequence analysis showed that no normal, stable allele
      contained more than 27 uninterrupted GAA triplets. All longer normal alleles were
      interrupted by a hexanucleotide repeat (GAGGAA). An allele containing an
      uninterrupted run of 34 GAA triplets was stably transmitted in four instances,
      but in one case underwent hyperexpansion to 650 triplets. Overall, our results
      suggest that the FRDA-associated expanded GAA repeats originate from normal
      alleles by recurrent expansions of alleles at risk.

PMID- 9259272
TI  - Cloning, mRNA distribution and chromosomal localisation of the gene for glial
      cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor
      for central dopaminergic neurons, motor neurons and several other populations of
      neurons in the central and peripheral nervous system. GDNF and its receptor
      complex of c-RET tyrosine kinase and a glycosyl-phosphatidylinositol linked
      protein GDNFR-alpha are of great interest due to their potential use in the
      therapy of Parkinson's and motoneuron diseases. We have cloned the human and rat
      cDNA sequences of GDNFR-beta, a new gene encoding for a 464 amino acid long
      homologue of GDNFR-alpha, and assign the locus of this new gene to human
      chromosome 8p21-22 and mouse chromosome 14D3-E1. Similarly to GDNFR-alpha, GDNFR
      beta mediates GDNF-induced Ret autophosphorylation in transfected cells. By
      northern hybridisation we show that the transcript level of human GDNFR-beta mRNA
      is high in the adult brain, intestine and placenta and in fetal brain, lung and
      kidney. Studied by in situ hybridisation, GDNFR-beta mRNA shows in E17 rat embryo
      different distribution to that of GDNFR-alpha mRNA, especially, in adrenal gland,
      kidney and gut. In the developing nervous system, GDNFR-beta mRNA expression is
      restricted to certain neuronal populations, while GDNFR-alpha mRNA is widely
      expressed also in non-neuronal cells. The distinct tissue distribution of GDNFR
      beta mRNA and its ability to mediate GDNF signal in transfected cells suggest a
      role in signal transduction of GDNF and, possibly, related neurotrophic factors
      in vivo.

PMID- 9259274
TI  - Molecular features of the CAG repeats of spinocerebellar ataxia 6 (SCA6).
AB  - Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar
      degeneration caused by the expansion of the polymorphic CAG repeat in the human
      alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4 gene). We have
      analyzed 60 SCA6 individuals from 39 independent SCA6 Japanese families and found
      that the CAG repeat length is inversely correlated with the age of onset (n = 58,
      r = -0.51, P < 0.0001). SCA6 chromosomes contained 21-30 repeat units, whereas
      normal chromosomes displayed 6-17 repeats. There was no overlap between the
      normal and affected CAG repeat number. The anticipation of the disease was
      observed clinically in all eight parent-child pairs that we examined; the mean
      age of onset was significantly lower (P = 0.0042) in children than in parents.
      However, a parent-child analysis showed the increase in the expansion of CAG
      repeats only in one pair and no diminution in any affected cases. This result
      suggests that factors other than CAG repeats may produce the clinical
      anticipation. A homozygotic case could not demonstrate an unequivocal gene dosage
      effect on the age of onset.

PMID- 9259273
TI  - Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms
      in multiple ethnic groups.
AB  - Linkage disequilibrium (association) analysis was used to evaluate a candidate
      region near the CTLA4/CD28 genes using a multi-ethnic collection of families with
      one or more children affected by IDDM. In the data set unique to this study
      (Spanish, French, Mexican-American, Chinese and Korean), the
      transmission/disequilibrium test (TDT) revealed a highly significant deviation
      for transmission of alleles at the (AT)n microsatellite marker in the 3'
      untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P =
      0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of
      the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined
      data set (669 multiplex and 357 simplex families) from this study and a previous
      report on families from USA, Italy, UK, Spain and Sardinia. Significant
      heterogeneity was observed in these data sets. The British, Sardinian and Chinese
      data sets did not show any deviation for the A/G polymorphism, while the
      Caucasian-American data set showed a weak transmission deviation. Strong
      deviation for transmission was seen in the three Mediterranean-European
      populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American
      population (P = 0.002) and the Korean population (P = 0.03). These results
      suggest that a true IDDM susceptibility locus (designated IDDM12) is located near
      CTLA4.

PMID- 9259276
TI  - Generation of novel human MHC class II mutant B-cell lines by integrating YAC DNA
      into a cell line homozygously deleted for the MHC class II region.
AB  - The human B lymphoblastoid cell line (LCL) 721.174 sustains a large homozygous
      deletion in the major histocompatibility complex (MHC) class II region that
      results in an absence of DQ and DR molecules as well as a deficiency in the
      assembly and transport of class I molecules to the cell surface. The deleted
      genes include the transporters associated with antigen processing TAP1 and TAP2,
      DMA and DMB which are involved in editing class II bound peptides, and four genes
      whose roles in antigen processing are unclear; the low mass polypeptide genes
      LMP2 and LMP7, and DNA and DOB. To study this region we have integrated into
      721.174 two overlapping yeast artificial chromosome (YAC) clones which cover the
      interval LMP2-DRA inclusive. Three clones (11.2A1.1, 4D1D10.1 and 4D1D10.2),
      containing complete copies of the transfected YAC, produced varying levels of
      mRNA from the LMP, TAP, DQ and DR genes and corresponding levels of LMP and TAP
      protein. Class I cell surface expression was restored in 11.2A1.1 and 4D1D10.1,
      as was DR expression in both 4D1D10 transfectants. These studies demonstrate the
      feasibility of introducing large groups of functional genes back into human
      lymphoblastoid cells sustaining deletions, with full restoration of biological
      function. The procedure could be exploited in order to restore all but one gene
      covered by the deletion, effectively producing a single gene defect. This could
      be used to introduce copies of genes engineered to contain mutations and to study
      cis regulatory elements at some distance from the chosen loci.

PMID- 9259275
TI  - SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium
      channel gene.
AB  - Recently, moderate (CAG)>20 repeat expansions in the alpha1A-voltage-dependent
      calcium channel gene (CACNL1A4) have been identified in a previously unmapped
      type of SCA which has been named SCA6. We investigated the (CAG)n repeat length
      of the CACNL1A4 gene in 733 patients with sporadic ataxia and in 46 German
      families with dominantly inherited SCA which do not harbor the SCA1, SCA2, or
      MJD1/SCA3 mutation, respectively. The SCA6 (CAG)n expansion was identified in 32
      patients most frequently with late manifestation of the disease. The (CAG)n
      stretch of the affected allele varied between 22 and 28 trinucleotide units and
      is therefore the shortest trinucleotide repeat expansion causing spinocerebellar
      ataxia. The (CAG)n repeat length is inversely correlated with the age at onset.
      In 11 parental transmissions of the expanded allele no repeat instability has
      been observed. Repeat instability was also not found for the normal allele
      investigating 431 meioses in the CEPH families. Analyzing 248 apparently healthy
      octogenerians revealed one allele of 18 repeats which is the longest normal CAG
      repeat in the CACNL1A4 gene reported. The SCA6 mutation causes the disease in
      approximately 10% of autosomal dominant SCA in Germany. Most importantly, the
      trinucleotide expansion was observed in four ataxia patients without obvious
      family history of the disease which necessitates a search for the SCA6 (CAG)n
      expansion even in sporadic patients.

PMID- 9259277
TI  - Sequence comparison of human and yeast telomeres identifies structurally distinct
      subtelomeric domains.
AB  - We have sequenced and compared DNA from the ends of three human chromosomes: 4p,
      16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate
      (TTAGGG)n repeats into distal and proximal sub-domains with entirely different
      patterns of homology to other chromosome ends. The distal regions contain
      numerous, short (<2 kb) segments of interrupted homology to many other human
      telomeric regions. The proximal regions show much longer (approximately 10-40 kb)
      uninterrupted homology to a few chromosome ends. A comparison of all yeast
      subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG
      repeats into distal and proximal sub-domains with similarly different patterns of
      identity to other non-homologous chromosome ends. Sequence comparisons indicate
      that the distal and proximal sub-domains do not interact with each other and that
      they interact quite differently with the corresponding regions on other, non
      homologous, chromosomes. These findings suggest that the degenerate TTAGGG
      repeats identify a previously unrecognized, evolutionarily conserved boundary
      between remarkably different subtelomeric domains.

PMID- 9259278
TI  - Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and
      testis.
AB  - Lack of expression of the fragile X mental retardation protein (FMRP) results in
      mental retardation and macroorchidism, seen as the major pathological symptoms in
      fragile X patients. FMRP is a cytoplasmic RNA-binding protein which cosediments
      with the 60S ribosomal subunit. Recently, two proteins homologous to FMRP were
      discovered: FXR1 and FXR2. These novel proteins interact with FMRP and with each
      other and they are also associated with the 60S ribosomal subunit. Here, we
      studied the expression pattern of the three proteins in brain and testis by
      immunohistochemistry. In adult brain, FMR1, FXR1 and FXR2 proteins are
      coexpressed in the cytoplasm of specific differentiated neurons only. However, we
      observed a different expression pattern in fetal brain as well as in adult and
      fetal testis, suggesting independent functions for the three proteins in those
      tissues during embryonic development and adult life.

PMID- 9259279
TI  - XIST expression from the maternal X chromosome in human male preimplantation
      embryos at the blastocyst stage.
AB  - In the somatic cells of female mammals, either the maternally or paternally
      derived X chromosome (X(M) or X(P)) is randomly inactivated to achieve dosage
      compensation for X-linked genes. In early mouse development, however, selective
      inactivation of X(P) occurs first in extraembryonic lineages at the blastocyst
      stage around the time of implantation before later random inactivation in the
      embryonic ectoderm from which the fetus is derived. Xist, a gene mapping to the X
      inactivation centre (Xic), is exclusively expressed from the inactive X
      chromosome and is thought to be involved in the initiation of X-inactivation.
      Consistent with this, Xist is first expressed at the 4-to 8-cell stages, prior to
      functional inactivation at the blastocyst stage, exclusively from X(P) in female
      embryos. This also suggests that genomic imprinting may influence the earliest
      expression of Xist resulting in selective inactivation of X(P) and a candidate
      methylation site in the promoter region has recently been described. Here we
      report the expression of the human homologue, XIST, in human preimplantation
      embryos from the 5- to 10-cell stage onwards consistent with its role in the
      initiation of inactivation. In contrast to the mouse, however, transcripts were
      detected in both male and female embryos demonstrating XIST expression from the
      X(M) in male embryos (X(M)Y).

PMID- 9259280
TI  - Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy
      on chromosome 15q.
AB  - The epilepsies are a group of disorders characterised by recurrent seizures
      caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up
      to 60 million people are affected worldwide and genetic factors may contribute to
      the aetiology in up to 40% of patients. The most common human genetic epilepsies
      display a complex pattern of inheritance. These are categorised as idiopathic in
      the absence of detectable structural or metabolic abnormalities. Juvenile
      myoclonic epilepsy (JME) is a distinctive and common variety of familial
      idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a
      ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular
      genetic basis of these familial idiopathic epilepsies is entirely unknown, but a
      mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal
      nicotinic acetylcholine receptor (nAChR), was recently identified in a rare
      Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes
      for nAChR subunits were therefore tested for linkage to the JME trait in 34
      pedigrees. Significant evidence for linkage with heterogeneity was found to
      polymorphic loci encompassing the region in which the gene encoding the alpha7
      subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65;
      Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic
      susceptibility to JME in a majority of the families studied.

PMID- 9259281
TI  - Linkage analysis of candidate regions for coeliac disease genes.
AB  - A strong HLA association is seen in coeliac disease [specifically to the
      DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the
      increased risk seen in relatives of affected cases. One or more genes at HLA
      unlinked loci also predispose to coeliac disease and are probably stronger
      determinants of disease susceptibility than HLA. A recent study has proposed a
      number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27,
      5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the
      location of a non-HLA linked susceptibility gene. We have examined these regions
      in 28 coeliac disease families by linkage analysis. There was excess sharing of
      chromosome 6p markers, but no support for a predisposition locus telomeric to
      HLA. No significant evidence in favour of linkage to coeliac disease was obtained
      for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen.
      There was, however, excess sharing close to D15S642. The maximum non-parametric
      linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac
      disease to chromosome 15q26 is not strong, the well established association
      between coeliac disease and insulin dependent diabetes mellitus, together with
      the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide
      indirect support for this as a candidate locus conferring susceptibility to
      coeliac disease in some families.

PMID- 9259282
TI  - PHOG, a candidate gene for involvement in the short stature of Turner syndrome.
AB  - The abnormalities seen in Turner syndrome (monosomy X) presumably result from
      haploinsufficiency of certain genes on the X chromosome. Gene dosage
      considerations lead to the prediction that the culpable genes escape X
      inactivation and have functional homologs on the Y chromosome. Among the genes
      with these characteristics are those residing in the pseudoautosomal regions
      (PAR) of the sex chromosomes. A pseudoautosomal location for a dosage-sensitive
      locus involved in stature has been suggested based on the analyses of patients
      with deletions of a specific segment of the short arm PAR; hemizygosity for this
      putative locus probably also contributes to the short stature in Turner
      individuals. We have isolated a gene from the critical deleted region that
      encodes a novel homeodomain-containing transcription factor and is expressed at
      highest levels in osteogenic cells. We have named the gene PHOG, for
      pseudoautosomal homeobox-containing osteogenic gene. Its deletion in patients
      with short stature, the predicted altered dosage in 45,X individuals, along with
      the nature of the encoded protein and its expression pattern, make PHOG an
      attractive candidate for involvement in the short stature of Turner syndrome. We
      have also found that the mouse homolog of PHOG is autosomal, which may help to
      explain the lack of a growth abnormality in mice with monosomy X.

PMID- 9259283
TI  - Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel
      candidate regions (16q and 20p) by genome-wide scan.
AB  - In a 12.5 cM genome-wide scan for psoriasis susceptibility loci, recombination
      based tests revealed linkage to the HLA region (Zmax = 3.52), as well as
      suggestive linkage to two novel regions: chromosome 16q (60-83.1 cM from pter,
      Zmax = 2.50), and chromosome 20p (7.5-25 cM from pter, Zmax = 2.62). All three
      regions yielded P values < or = 0.01 by non-parametric analysis. Recombination
      based and allele sharing methods also confirmed a previous report of a dominant
      susceptibility locus on distal chromosome 17q (108.2 cM from pter, Zmax = 2.09,
      GENEHUNTER P = 0.0056). We could not confirm a previously reported locus on
      distal chromosome 4q; however, a broad region of unclear significance was
      identified proximal to this proposed locus (153.6-178.4 cM from pter, Zmax =
      1.01). Taken together with our recent results demonstrating linkage to HLA-B and 
      C, this genome-wide scan identifies a psoriasis susceptibility locus at HLA,
      confirms linkage to 17q, and recommends two novel genomic regions for further
      scrutiny. One of these regions (16q) overlaps with a recently-identified
      susceptibility locus for Crohn's disease. Psoriasis is much more common in
      patients with Crohn's disease than in controls, suggesting that an
      immunomodulatory locus capable of influencing both diseases may reside in this
      region.

PMID- 9259284
TI  - A high frequency African coding polymorphism in the N-terminal domain of ICAM-1
      predisposing to cerebral malaria in Kenya.
AB  - The malarial parasite Plasmodium falciparum has acted as a potent selective force
      on the human genome. The particular virulence of this organism is thought to be
      due to the adherence of parasitised red blood cells to small vessel endothelium
      through several receptors, including CD36, thrombospondin and intercellular
      adhesion molecule 1 (ICAM-1, CD54), and parasite isolates differ in their ability
      to bind to each. Immunohistochemical studies have implicated ICAM-1 as of
      potential importance in the pathogenesis of cerebral malaria, leading us to
      reason that if any single receptor were involved in the development of cerebral
      malaria, then in view of the high mortality of that complication, natural
      selection should have produced variants with reduced binding capacity. We
      therefore sequenced the N-terminal domain of ICAM-1 from a number of Africans and
      discovered a single mutation present at high frequency. Genotypes at this locus
      from samples from a case-control study indicated an association of the
      polymorphism with the severity of clinical malaria such that individuals
      homozygous for the mutation have increased susceptibility to cerebral malaria
      with a relative risk of two. These counterintuitive results have implications for
      the mechanism of malaria pathogenesis, resistance to other infectious agents and
      transplantation immunology.

PMID- 9259285
TI  - Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha
      subunit gene.
AB  - In a significant number of patients with biochemical evidence of a defect in the
      E1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex, it
      has not proved possible to identify a mutation in the gene coding regions. To
      assess the need for more extensive genetic analysis in these patients and to
      establish a test system in which to study the biochemical consequences of
      mutations in the E1alpha subunit gene (which is responsible for the great
      majority of defined cases of pyruvate dehydrogenase deficiency), we have
      developed a method to screen for E1alpha gene defects based on complementation of
      the enzyme deficiency in transformed fibroblast cell lines following transfection
      and expression of the normal cDNA. Using this system, cell lines from patients
      with a variety of different defined mutations in the E1alpha gene show
      restoration of enzyme activity. A number of patients have been identified in whom
      deficient enzyme activity is not restored by expression of the normal cDNA
      indicating that an alternative explanation for the enzyme defect must be sought.

PMID- 9259286
TI  - The TWIST gene, although not disrupted in Saethre-Chotzen patients with
      apparently balanced translocations of 7p21, is mutated in familial and sporadic
      cases.
AB  - The TWIST gene maps to 7p21 and mutations in the gene have been reported in the
      Saethre-Chotzen form of craniosynostosis. The position of the Saethre-Chotzen
      gene has previously been refined by FISH analysis of four patients carrying
      balanced translocations involving 7p21 which suggested that it was located
      between D7S488 and D7S503. We report here that the breakpoints in four
      translocation patients do not interrupt the coding sequence of the TWIST gene and
      thus most likely act through a positional effect. Twelve Saethre-Chotzen cases
      were found to have TWIST mutations. Four of these families had been used as part
      of the linkage study of the Saethre-Chotzen locus. The mutations detected
      included missense and nonsense mutations and three cases of a 21 bp duplication.
      Although phenotypically diagnosed as having Saethre-Chotzen syndrome, three
      families were found to have a pro250arg mutation of FGFR3.

PMID- 9259287
TI  - Human mini-chromosomes in mouse embryonal stem cells.
AB  - We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb in size
      into mouse embryonal stem cells. Although these human mini-chromosomes are stable
      in hamster and chicken cells, they re-arrange or segregate aberrantly in the
      embryonal stem cells and are rapidly lost in the absence of selection. However,
      one of the mini-chromosomes re-arranged, acquired mouse centromeric sequences and
      was then stably maintained for at least 60 population doublings in culture. This
      mini-chromosome, which is 4 Mb in size, is a candidate for a mouse germ line
      chromosome vector.

PMID- 9259289
TI  - Economic evaluation in medicine.

PMID- 9259288
TI  - Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease.
AB  - Cowden disease, also known as multiple hamartoma syndrome, is an autosomal
      dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene
      involved has been localized to chromosome 10q22-23. Recently, the tumour
      suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual
      specificity phosphatase, was cloned from that region and three mutations were
      detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene
      is indeed the gene for Cowden disease by a refined localization of the gene to
      the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene
      and, by mutation analysis in eight unrelated familial and 11 sporadic patients
      with Cowden disease. Eight different mutations were detected in various regions
      of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in
      the gene can be predicted to have a very deleterious effect on the putative
      protein. Five of the nine patients have a mutation in exon 5 coding for the
      putative active site and flanking amino acids. Evaluation of the clinical data of
      the patients in which a mutation could be detected gives no clear indications for
      a correlation between the genotype and phenotype. In 10 patients no mutation
      could be detected so far. In support of the linkage data, no evidence has emerged
      from the phenotype of these patients suggestive for genetic heterogeneity.

PMID- 9259291
TI  - The role of diet and behaviour in childhood.
AB  - This short review summarizes the most important research, particularly that from
      1985 to 1995, on the relationship between diet and behaviour. Relevant studies
      particularly those using double-blind placebo controlled food challenge
      methodology were selected, and are presented within a historical context. Summary
      tables of the early development of concepts and later pertinent studies are
      provided. The research has shown that diet definitely affects some children.
      Rather than becoming simpler the issue has become demonstrably more complex. The
      range of suspect food items has broadened, and some non-food items are relevant.
      Symptoms which may change include those seen in attention deficit disorder (ADD)
      and attention deficit hyperactivity disorder (ADHD), sleep problems and physical
      symptoms, with later research emphasizing particularly changes in mood. The
      reports also show the range of individual differences both in the food substances
      producing reactions and in the areas of change.

PMID- 9259290
TI  - Deficiency of substance P-immunoreactive nerve fibres in children with
      intractable constipation: a form of intestinal neuronal dysplasia.

PMID- 9259292
TI  - Recent advances in diagnosis of the childhood muscular dystrophies.
AB  - Recent advances in molecular genetics research have revolutionised our
      understanding of the childhood muscular dystrophies. The first breakthrough came
      in 1987 with the identification of the gene for dystrophin, the protein that is
      abnormal in X-linked Duchenne muscular dystrophy. Dystrophin is bound to a
      complex of proteins in the muscle membrane, and primary abnormalities of these
      proteins have now been identified as the cause of some autosomally inherited
      forms of muscular dystrophy. A group of transmembrane proteins known as alpha-
      (adhalin) beta-, gamma- and delta-sarcoglycan are deficient in autosomal
      recessive limb-girdle muscular dystrophy, and the extracellular matrix protein
      merosin (alpha2-laminin), is deficient in a subset of patients with congenital
      muscular dystrophy. Identification of primary deficiencies in these 'dystrophin
      associated proteins' will result in improved diagnostic accuracy, more accurate
      genetic counselling and, in some cases, the availability of prenatal diagnosis.

PMID- 9259293
TI  - Economic outcome for intensive care of infants of birthweight 500-999 g born in
      Victoria in the post surfactant era. The Victorian Infant Collaborative Study
      Group.
AB  - OBJECTIVE: To determine the incremental cost of improving the outcome for
      extremely low birthweight (ELBW, birthweight 500-999 g) infants born in Victoria
      after the introduction of exogenous surfactant (the post surfactant era).
      METHODOLOGY: This was a geographically determined cohort study of ELBW children
      in Victoria, Australia of consecutive livebirths born in three distinct eras: (i)
      1979-80 (n = 351); (ii) 1985-87 (n = 560); and (iii) 1991-92 (n = 429). Exogenous
      surfactant was first used in Victoria in March, 1991. The consumption of nursery
      resources per livebirth, and the survival and sensorineural disability rates at 2
      years of age for each era were investigated. Utilities were assigned as follows:
      0 for dead, 0.4 for severe disability, 0.6 for moderate disability, 0.8 for mild
      disability, and 1 for no disability. Utilities were multiplied for more than one
      disability. Dollar costs were assumed to be $1470 ($A 1992) per day of assisted
      ventilation, and one dose of exogenous surfactant was assumed to be equivalent to
      one third of a day of assisted ventilation. Cost-effectiveness (additional costs
      per additional survivor or life-year gained) and cost-utility (additional costs
      per additional quality-adjusted survivor or life-year gained) ratios were
      calculated for the pre-surfactant era (1985-87 vs 1979-80), and for the post
      surfactant era (1991-92 vs 1985-87). RESULTS: Considering only the costs incurred
      during the primary hospitalization, cost-effectiveness and cost-utility ratios
      were lower (i.e. economically better) in the post surfactant era than in the pre
      surfactant era (pre-surfactant vs post surfactant; $7040 vs $4040 per life year
      gained; $6700 vs $5360 per quality-adjusted life year gained). Both ratios fell
      with increasing birthweight. In contrast with the pre-surfactant era, cost
      utility ratios were less favourable than cost-effectiveness ratios in the post
      surfactant era. With costs for long-term care of severely disabled children
      added, both cost ratios were higher in the post surfactant era. CONCLUSION: The
      incremental cost during the primary hospitalization of improving the outcome for
      ELBW infants has fallen in the post surfactant era.

PMID- 9259294
TI  - Calcium intake in children with positive IgG RAST to cow's milk.
AB  - OBJECTIVE: This study was made to: (i) identify the prevalence of low calcium
      intakes in a paediatric population with loosely defined 'milk allergy'; and (ii)
      assess long-term (mean 21 months later) changes in calcium intake following a
      single nutrition counselling session with those patients initially found to have
      a low intake. METHODOLOGY: Calcium intake was assessed in a cross-sectional study
      of 58 patients ages 5-16 years (mean 9.9 years) with IgG radioallergosorbent test
      (RAST) class II or higher for cow's milk protein. Those 31 patients found to have
      a low calcium intake were prospectively re-evaluated 12-30 months later following
      a single nutrition counselling session. RESULTS: Calcium intake was < recommended
      dietary allowance (RDA) for 31 of 58 (53%) patients. The patient's perception of
      their intake was unreliable; 44% of those who rated their calcium intake fair or
      good did not meet their RDA. Taking a calcium supplement did not ensure adequate
      intake; 21% of those taking supplements still did not meet their RDA. Milk intake
      predicted calcium intake; 8% of those who did not drink milk vs 68% of those who
      did drink at least some milk met their RDA without supplementation. The 31
      patients with low intakes received counselling and were re-evaluated at an
      average follow-up of nearly 2 years. Calcium intake was increased a mean of 360
      mg/day and use of supplements increased from 10 to 52% of the group. Despite
      these positive changes, 48% still did not meet their RDA. CONCLUSION: Limited
      milk intake is likely to be associated with suboptimal calcium intake. Efforts
      should be made to educate the family about the importance of calcium and its non
      dairy sources. With many families repeated discussions of this issue may be
      necessary to influence calcium intake.

PMID- 9259295
TI  - Aetiology and classification of small for gestational age infants.
AB  - OBJECTIVE: To determine important aetiological factors in small gestational age
      (SGA) infants and the effectiveness of anthropometric indexes in identifying
      patterns of growth retardation. METHODOLOGY: Eighty-four SGA infants and 81
      controls were enrolled. Maternal biological, lifestyle and psychosocial factors
      were compared for the total group and the term Caucasian subset. Anthropometric
      indexes were also examined in relation to growth patterns. RESULTS: Decreased
      maternal size, poor weight gain, previous SGA infant and smoking were
      significantly associated with SGA status. Poor parental education and
      unemployment was increased in the study group. Mothers of SGA infants, especially
      the term Caucasian group, had a greater prevalence of hypertension and depressive
      and stress symptomatology. Ponderal index failed to identify discreet patterns of
      disproportionate/proportionate growth retardation. CONCLUSION: Biological,
      lifestyle and psychosocial differences remain important aetiological factors of
      intrauterine growth retardation. Identification of specific patterns of growth
      retardation by ponderal index remains controversial.

PMID- 9259296
TI  - Treatment characteristics of congenital heart disease and behaviour problems of
      patients and healthy siblings.
AB  - OBJECTIVE: To examine behaviour problems of children in families where one child
      was diagnosed with congenital heart disease (CHD), in relation to the intensity
      of treatment required for the CHD. METHODOLOGY: Treatment intensity was based on
      patients' hospitalizations, surgical operations, current treatment, frequency of
      check-ups and finality of surgical repair. Mothers of 29 patients and 43 healthy
      siblings (4-14 years old), and a sub-sample of fathers, reported on behaviour
      problems of their children and rated the frequency of considering patient's CHD
      while performing routine child care in nine areas of family life (accommodation
      of illness). RESULTS: High treatment intensity was associated with high
      accommodation of illness and elevated behaviour problems among patients. In
      contrast, siblings in families where treatment intensity was low, but
      accommodation of illness high were at most risk for behaviour problems.
      CONCLUSIONS: Treatment intensity has a markedly different impact on behaviour
      problems of patients and healthy siblings. It is important for parents and
      healthcare professionals to provide both patients and siblings with information
      about the patient's medical condition, regardless how much treatment that
      condition may need.

PMID- 9259297
TI  - Trends of infant mortality in Hong Kong (1956-90) and evaluation of preventable
      infant deaths.
AB  - OBJECTIVE: This study describes the time trends for infant mortality in Hong Kong
      and aims to develop statistical models that can be used to predict changes of
      infant mortality in places already having low levels of infant mortality.
      METHODOLOGY: Data on births and deaths of infants in Hong Kong during the years
      1956-90 were analysed annually as well as by aggregating the data into seven
      consecutive quinquennia. To assess the contribution of preventable infant deaths,
      causes for infant deaths were classified into two broad categories: (i)
      congenital anomalies; and (ii) preventable diseases. A simple linear regression
      model was used to analyse the time trend of the mortality rate of the preventable
      diseases (PIMR) over the seven quinquennia. RESULTS: During the period 1956-90,
      the infant mortality rate fell from 60.9 in 1956-5.9 per 1000 in 1990 and the
      neonatal mortality rate fell from 24.2-3.8 per 1000. There was no clear time
      trend observed for infant mortality of congenital anomalies. However, the time
      trend for PIMR (log scale) was very close to a straight line and simple linear
      regression modelling showed a R2 of 0.9970. CONCLUSION: As the infant mortality
      rate (IMR) falls to below 30 per 1000, the further rate of decrease becomes less
      predictable from the regression model of the IMR. By removing the portion of
      deaths attributable to congenital anomalies, the further decrease in infant
      mortality became more predictable down to very low levels of IMR.

PMID- 9259298
TI  - A review of open biopsy for mediastinal masses.
AB  - OBJECTIVE: To review the recent experience with biopsied mediastinal lesions in
      children and to assess the impact of recent advances in imaging and surgical
      techniques on diagnosis. METHODOLOGY: The clinical and radiological features of
      55 patients who had mediastinal biopsies at The Royal Alexandra Hospital For
      Children (RAHC) over 15 years were reviewed. RESULTS: Fifty-five patients
      presented to RAHC between 1978 and 1993 with lesions of the mediastinum requiring
      biopsy of that site. Thirty-one of the 55 (56%) lesions were malignant.
      Neurogenic tumours were the most common (40%). In order of frequency the
      following lesions were found: neuroblastoma (15), teratoma (eight), non-Hodgkin's
      lymphoma (NHL; eight), enteric cyst/duplication (five), ganglioneuroma (five),
      bronchogenic cyst (three), ganglioneuroblastoma (two), lymphangioma (two),
      abscess (two), Hodgkin's lymphoma (HL; two), oesophageal granuloma (one),
      Langerhan's cell histiocytosis (one), congenital fibromatosis (one). Eighty-two
      per cent of neurogenic tumours were located in the posterior mediastinum, while
      75% of teratomas and 100% lymphoid tumours were located anteriorly. Symptoms were
      generally unhelpful in establishing a specific diagnosis and in 27% of cases the
      lesions were discovered incidentally. Physical signs, such as thoracic inlet
      obstruction and neurological findings, were helpful clinically in localizing
      lesions within the mediastinum. Chest radiography enabled lesions to be
      subdivided within the mediastinum. This localization, in combination with the age
      at presentation, predicted the tissue diagnosis. Computerized tomography (CT) and
      magnetic resonance imaging (MRI) further defined the lesion and demonstrated
      involvement of adjacent structures. Histology, however, was essential to
      distinguish benign from malignant lesions. CONCLUSIONS: The clinical presentation
      of mediastinal masses is often non-specific or incidental. Despite recent
      advances in imaging technology and biopsy techniques, full histological
      examination is required to exclude malignancy.

PMID- 9259299
TI  - Sunburn and sun protection among young children.
AB  - OBJECTIVE: To examine the extent of sun exposure, sun protection and experience
      of sunburn among young New Zealand children on summer weekends. METHODS: In a
      telephone survey of 1243 respondents, those with children in the household were
      asked about sun exposure and protection for the youngest child in the family.
      Information was obtained for 285 children aged from infancy to 10 years. RESULTS:
      Over 90% of the children were reported to be outside on the preceding Saturday
      and/or Sunday; 7% of those outside experienced some degree of sunburn. The worst
      burning was on the face, head, neck or ears. On either day about half the
      children were wearing sunscreen and 60% were wearing a hat. Parental use of sun
      protection was the strongest predictor of sun protection among the children.
      CONCLUSIONS: While reports of sun protection among young children were
      encouraging, many children in the community are still at high risk of sunburn.
      Efforts to promote sun protection as a family responsibility may reduce the
      experience of burning among the young.

PMID- 9259300
TI  - The prevalence of hepatitis C in survivors of paediatric malignancy.
AB  - OBJECTIVE: To assess the prevalence of hepatitis C in 200 patients with
      paediatric malignancies, surviving in remission more than 5 years from diagnosis,
      who had received blood product transfusions before 1990 when routine screening of
      blood products for hepatitis C began. METHOD: The second and third generation
      Abbott Diagnostics ELISA was used to assess hepatitis C seropositivity.
      Seropositive patients and those with abnormal liver transaminases were assessed
      by hepatitis C virus RNA polymerase chain reaction (PCR). RESULTS: A low
      incidence (4%) of seropositivity for hepatitis C was found in survivors of
      paediatric malignancy who were transfused prior to routine screening of blood
      products in this cohort. CONCLUSIONS: All patients identified have evidence of
      hepatitis and may be at high risk of developing cirrhosis.

PMID- 9259301
TI  - Changes in serum lipids and lipoproteins in epileptic children treated with
      anticonvulsants.
AB  - OBJECTIVE: To assess the effect of long-term treatment of phenobarbital,
      carbamazepine and sodium valproate on serum lipids and lipoproteins in epileptic
      children. METHODOLOGY: One hundred and fourteen (55 male, 59 female) children and
      adolescents suffering from various types of epilepsy who received different
      antiepileptic drugs were studied. The patients were subdivided into three groups
      according to their therapy: (i) carbamazepine (35 patients); (ii) phenobarbital
      (34 patients); and (iii) sodium valproate (45 patients). One-hundred healthy sex-
      and age-matched children served as controls. Lipids and lipoprotein profile were
      evaluated before the beginning of the anticonvulsant therapy and after at least
      2.5 years. In the patients receiving phenobarbital, we re-evaluated 12 children
      (seven male, five female) at the end of therapy. RESULTS: The children receiving
      phenobarbital showed high levels of serum total cholesterol and low-density
      lipoprotein (LDL) cholesterol and low levels of triglycerides, while children
      treated with carbamazepine had high levels of total cholesterol, triglycerides,
      LDL and high-density lipoprotein (HDL) cholesterol. Children treated with
      valproate had low triglycerides and LDL cholesterol levels with high levels of
      HDL cholesterol. The patients treated with phenobarbital showed a normalization
      of all parameters after the end of therapy. CONCLUSIONS: Anticonvulsant drugs
      significantly modify serum lipids and lipoproteins in epileptic children. The
      changes due to phenobarbital seem to be transient.

PMID- 9259302
TI  - Acute renal failure in the newborn: incidence and outcome.
AB  - OBJECTIVE: To describe an experience from a developing country of newborn renal
      disease particularly those without advanced neonatal care. METHODOLOGY:
      Prospective evaluation from a referral hospital, North-East of Nigeria between 1
      July 1990 and 30 June 1994. Babies admitted for any morbidities who were
      diagnosed as being in acute renal failure (ARF) during the study period (non
      oliguric inclusive). Onset of ARF; day on which oliguria or anuria detected, or
      serum urea first exceeded 10 mmol/L. Urine output quantitated from carefully
      bagged urine and suprapubic bladder aspiration, and venous blood regularly
      obtained for serum electrolytes, urea and creatinine. Fractional excretion of
      sodium (FE(Na)) and renal failure index (RFI) were determined on some babies.
      RESULTS: Forty-three neonates (M:F; 3.3:1) with ARF, the majority (27) of whom
      were out-born, and 14, 26 and three were preterm, full-term and post term,
      respectively. Encountered incidence was 3.9/1000 live births with a high
      prevalence rate; 34.5/1000 admissions. A significantly greater incidence was seen
      in the latter half of study; 10.7 vs 53.7/1000, P < 0.05. Early ARF occurrence
      (aged; 0-5 days) in 33 (77%) of babies. The aetiology was comprised of perinatal
      asphyxia, sepsis, obstructive uropathy and miscellaneous in 53.4%, 32.6%, 9.3%
      and 4.7%, respectively. Twenty-two (51.2%) deaths occurred; however, the exact
      causes were indeterminable. Fractional excretion of sodium (FE(Na)) and renal
      failure index (RFI) were of < 1.75% and < or = 2.0, respectively, significantly
      differentiated sepsis (intrinsic) from perinatal asphyxial (pre-renal) ARF; P <
      0.01. No case of persistent renal failure occurred. CONCLUSION: Our FE(Na) value
      (although less than reported in previous literature from affluent societies)
      remained sensitive (along with RFI) in differentiating aetiological group of ARF.
      Our data and medical management outcome, despite absence of level-III care,
      support the need for good resuscitation, careful monitoring and constant re
      evaluation. The effect of salbutamol on hyperkalaemia is emphasized.

PMID- 9259303
TI  - Minimal haemolysis in blood co-infused with amino acid and dextrose solutions in
      vitro.
AB  - OBJECTIVE: To examine the haemolytic effects of amino acid and dextrose solutions
      on co-infused packed red blood cells. METHODOLOGY: An in vitro study of packed
      cells co-infused at various rates with dextrose 5%, 10%, 15% and intravenous
      amino acid solution (Vamin; Kabi-Pharmacia, Baxter Healthcare Pty Ltd) in
      dextrose 5%, 10% and 15%. The degree of haemolysis was measured as free
      oxyhaemoglobin by spectrophotometer. Co-infused 0.9% saline and water were used
      as 0% and 100% haemolysis controls. RESULTS: Only minimal haemolysis was observed
      with the solutions tested. The greatest observed amount of haemolysis was 0.14%.
      CONCLUSIONS: Co-infusion of packed red blood cells with dextrose and amino acid
      solutions at the concentrations and infusion rates commonly used in neonatal
      care, does not cause clinically important haemolysis.

PMID- 9259304
TI  - Persistent hypercholesterolaemia in frequently relapsing steroid-responsive
      nephrotic syndrome.
AB  - OBJECTIVE: To investigate long-term changes of serum cholesterol levels in
      children with frequently relapsing steroid-responsive nephrotic syndrome (NS).
      METHODOLOGY: Serum cholesterol values just before and during or immediately after
      'relapse' were reviewed and the incidence of hypercholesterolaemia (> or = 200
      mg/dL) was determined in eight patients (M:F, 6:2). RESULTS: The patients with
      frequently relapsing NS usually showed hypercholesterolaemia (mean incidence,
      81%) just before 'relapse' during clinical remission, as well as in relapse (mean
      incidence, 96%). A high incidence of steroid therapy was also found in each case
      (mean, 89%) just before relapse. CONCLUSIONS: Our results demonstrate that
      children with frequently relapsing NS have prolonged periods of
      hypercholesterolaemia, even during clinical remission. It is suggested that serum
      lipid profiles be monitored carefully in such patients.

PMID- 9259305
TI  - Subperiosteal orbital haematoma presenting as proptosis at birth.
AB  - We present a case report of a neonate with congenital subperiosteal orbital
      haematoma presenting with unilateral proptosis with review of current literature.
      The baby made an uneventful recovery following surgical drainage of the
      haematoma. This is the second report of orbital haematoma presenting at birth.
      Orbital haematoma should be considered in the newborn with unilateral proptosis.
      Early detection with computed tomography (CT) or magnetic resonance imaging (MRI)
      is required to determine the need for surgical drainage.

PMID- 9259306
TI  - Steroid 17alpha-hydroxylase deficiency: first Australian case report.
AB  - 17alpha-hydroxylase deficiency is a rare form of congenital adrenal hyperplasia
      (CAH) that affects both glucocorticoid and sex hormone biosynthesis. We report a
      case of an unambiguous female with testes and hypertension. She was found to have
      deficient 17alpha-hydroxylase activity. The diagnosis was not made easily, the
      condition being unexpected due to its rarity. The discriminating feature of this
      form of sex-reversal is the presence of hypertension due to the elevated serum
      deoxycorticosterone levels. A failure to detect this will inappropriately focus
      attention on other, more common causes of sex reversal such as androgen
      insensitivity and gonadal dysgenesis, and expose the patient to the long-term
      sequelae of uncontrolled arterial hypertension.

PMID- 9259307
TI  - Disseminated pyomyositis with high creatine phosphokinase levels.
AB  - Pyomyositis is a rare purulent infection of skeletal muscle caused predominantly
      by Staphylococcus aureus. We report a patient who presented with high fever,
      widespread muscle pain and high creatine phosphokinase levels. He also developed
      multiple muscle and lung abscesses associated with a S. aureus septicaemia.

PMID- 9259308
TI  - Proteus syndrome.
AB  - This female Asian (Malay) baby had clinical features of Proteus syndrome. She had
      a large right facial lipolymphangioma with hyperpigmentation of the overlying
      skin. There was a smaller lymphangioma over the left side of her neck with excess
      nuchal folds, macrodactyly and bilateral talipes equinovarus. Despite the
      extensive hemifacial swelling, there was no evidence of upper respiratory tract
      obstruction. Generalized seizures developed on the sixth day of life which were
      controlled with phenobarbital. The lymphangiomas were excised without recurrence.

PMID- 9259309
TI  - Penicillium marneffei infection in a non-HIV infected child.
AB  - We report a case of Penicillium marneffei infection in a previously healthy 3.5
      years-old Chinese boy and review the literature. The details of the case are
      described with emphasis on his immune function and treatment outcome. This boy
      had transient immunodeficiency involving phagocytic and NK cells due to P.
      marneffei infection which resolved after treatment with gamma interferon and
      amphotericin B. A prolonged course of fluconazole of 1 year was successful in
      preventing relapse. Gamma interferon, amphotericin B and a prolonged course of
      fluconazole may be useful in the treatment of life-threatening infection by P.
      marneffei.

PMID- 9259310
TI  - Recurrence of chickenpox in an acyclovir-treated patient.

PMID- 9259312
TI  - Mutations of the conserved DRS motif in the second intracellular loop of the
      gonadotropin-releasing hormone receptor affect expression, activation, and
      internalization.
AB  - The GnRH receptor is an unusual member of the G protein-coupled receptor (GPCR)
      superfamily with several unique features. One of these is a variant of the
      conserved DRY motif that is located at the junction of the third transmembrane
      domain and the second intracellular (2i) loop of most GPCRs. In the GnRH
      receptor, the Tyr residue of the conserved triplet is replaced by Ser, giving a
      DRS sequence. The aspartate and arginine residues of the triplet are highly
      conserved in almost all GPCRs. The functional importance of these residues was
      evaluated in wild type and mutant GnRH receptors expressed in COS-7 cells.
      Mutants in which Asp138 was replaced by Asn or Glu were poorly expressed, but
      showed significantly increased internalization and exhibited augmented inositol
      phosphate generation to maximal agonist stimulation compared with the wild type
      receptor. In contrast, receptors in which Arg139 was substituted with Gln, Ala,
      or Ser showed reduced internalization, and the GnRH-induced inositol phosphate
      response for the Arg139Gln mutant was significantly impaired in proportion to its
      low expression level. Replacing Ser140 with Ala affected neither internalization
      nor signal transduction. The role of the polar amino acids at the C terminus of
      the 2i loop was evaluated in two additional mutants (Ser151Ala, Ser153Ala, and
      Ser151Ala, Ser153Ala, Lys154Gln, Glu156Gln). Both of these mutants exhibited
      agonist-induced inositol phosphate responses similar to that of the wild type
      receptor, but showed increased receptor internalization. This mutational analysis
      indicates that the conserved Asp and Arg residues in the DRY/S triplet make
      important contributions to the structural integrity of the receptor and influence
      receptor expression, agonist-induced activation, and internalization.

PMID- 9259311
TI  - CDK2 is a target for retinoic acid-mediated growth inhibition in MCF-7 human
      breast cancer cells.
AB  - Retinoic acid (RA) inhibition of breast cancer cell growth is associated with an
      accumulation of cells in G1 phase of the cell cycle. We have investigated the
      effects of RA on the expression and activity of cell cycle-regulatory proteins in
      MCF-7 human breast cancer cells. Flow cytometry analysis of MCF-7 cells treated
      with RA revealed a decrease in the percentage of cells in S phase by 48 h, which
      was maximal by 72 h. Phosphorylation of the retinoblastoma protein (pRb) was
      partially reduced in RA-treated cells accompanied by a decrease in the level of
      retinoblastoma protein. Expression of the cyclin D1 transcript was reduced by 48
      h and cyclin-dependent kinase 2 (cdk2) mRNA levels declined within 8 h
      posttreatment followed by a decrease in cyclin D1 and cdk2 protein levels.
      Message and protein levels of cdk4 and cdc2 were not affected by RA. While cdk4
      activity was similar in control and RA-treated cells, cdk2 activity began to
      decrease within 48 h of exposure to RA and was profoundly reduced after 72 h.
      This reduced activity was associated with decreased phosphorylation of cdk2. The
      decrease in cdk2 activity occurred in the absence of RA-mediated increases in the
      levels of the cdk inhibitors p21 and p27. However, assays of cdk2 from pooled
      lysates from RA-treated and control cells showed that RA-treated cells contain a
      cdk2-inhibitory activity. Our results show that RA inhibits cell cycle
      progression of MCF-7 cells by inhibiting cdk2 mRNA and protein production and by
      decreasing cdk2 activity.

PMID- 9259313
TI  - Phosphorylation of cbl after stimulation of Nb2 cells with prolactin and its
      association with phosphatidylinositol 3-kinase.
AB  - Stimulation of Nb2 cells with PRL results in the rapid phosphorylation of a 120
      kDa protein identified as the adapter protein cbl on tyrosine residues. Maximal
      phosphorylation of cbl occurs at 20 min after PRL stimulation and declines
      thereafter. Stimulation with as little as 5 nM PRL resulted in the
      phosphorylation of cbl; increasing the concentration of PRL to 100 nM had only a
      minimal effect upon the phosphorylation of cbl. The cbl protein appears to be
      constitutively associated with grb2 and the p85 subunit of phosphatidylinositol 3
      kinase (PI 3-kinase). The constitutive association of cbl with the p85 subunit of
      PI 3-kinase was observed in Nb2 cells as well as in 32Dcl3 cells transfected with
      either the rat Nb2 (intermediate) form of the PRL receptor or the long form of
      the human PRL receptor. A glutathione S-transferase fusion protein encoding the
      SH3 domain of the p85 subunit of PI 3-kinase bound to cbl in lysates of both
      unstimulated and PRL-stimulated Nb2 cells; however, neither of the SH2 domains of
      p85 bound to cbl under the same conditions. PRL stimulation increased the cbl
      associated PI kinase activity. The majority of PI kinase activity appeared to be
      cbl-associated after PRL stimulation. These results suggest that cbl may function
      as an adapter protein in PRL-mediated signaling events and regulate activation of
      PI 3-kinase. Our model suggests that the p85 subunit of PI 3-kinase is
      constitutively associated with cbl through binding of the p85 SH3 domain to a
      proline-rich sequence in cbl. After the tyrosine phosphorylation of cbl, an SH2
      domain(s) of p85 binds to a specific phosphorylation site(s) in cbl, leading to
      the activation of PI 3-kinase.

PMID- 9259314
TI  - Human chorionic somatomammotropin enhancer function is mediated by cooperative
      binding of TEF-1 and CSEF-1 to multiple, low-affinity binding sites.
AB  - The human chorionic somatomammotropin gene enhancer (CSEn) is composed of
      multiple enhansons (Enh) that share sequence similarities with those of the
      simian virus, SV40 enhancer (SVEn). The sequence homology includes two GT-IIC
      like (Enh1 and Enh4) and three SphI/II-like enhansons (Enh2, Enh3, and Enh5). We
      previously showed that transcription enhancer factor 1 (TEF-1) and a 30-kDa
      placental-specific factor, chorionic somatomammotropin enhancer factor 1 (CSEF
      1), bind to Enh4, which plays an essential role in enhancer function. In this
      study, we demonstrate that TEF-1 and CSEF-1 bind specifically to all the other GT
      IIC- and SphI/II-like elements within CSEn with a broad range of binding
      affinities that vary between 0.005 and 0.15 that of Enh4. Each individual
      concatenated enhanson was able to stimulate hCS promoter activity in an
      orientation-independent manner in choriocarcinoma cells (BeWo) with an observed
      stimulation that was directly proportional to its relative binding affinity for
      TEF-1 and CSEF-1. These results indicate that CSEn function results from the
      cooperative interaction of TEF-1 and/or CSEF-1 binding to multiple, low-affinity
      GT-IIC- and SphI/II-like enhansons within the enhancer.

PMID- 9259315
TI  - The human chorionic somatomammotropin enhancers form a composite silencer in
      pituitary cells in vitro.
AB  - The human GH (GH) gene family includes the pituitary-specific hGH-1, placental
      specific chorionic somatomammotropin (hCS-5, hCS-2, and hCS-1), and hGH-2 genes.
      These duplicated, nearly identical genes are localized on approximately 50 kb of
      DNA on chromosome 17q23-q24. An enhancer (CSEn2), located downstream of the hCS-2
      gene, participates in mediating placental-specific hCS gene expression. In the
      preceding paper we demonstrated that CSEn2 activity derives from the cooperative
      binding of transcription factor-1, TEF-1, and a placental-specific factor CSEF-1
      to multiple enhansons, Enh1-Enh5, that are related to the SV40 GT-IIC and
      SphI/SphII enhansons. Here we demonstrate that two copies of CSEn2 or a single
      copy of CSEn2 linked to either of the other two enhancers in the hGH/hCS locus,
      CSEn1 and CSEn5, act cooperatively to enhance hCS promoter activity in
      choriocarcinoma (BeWo) cells, but silence the promoter in pituitary GC cells.
      Mutation of Enh4, an essential GT-IIC-like enhanson in the context of the intact
      enhancer, abolishes silencer activity, and multimerized GT-IIC enhansons mimic
      the intact CSEn enhancer/silencer activities in BeWo and GC cells, respectively.
      By antibody-mediated supershift, Western, and far Western analyses, we identified
      TEF-1 as the GT-IIC-binding factor in pituitary cells. The data suggest that TEF
      1 may be involved in pituitary-specific repression of placental GH/CS gene
      transcription through long-range interactions between the multiple CS enhancers
      present on the GH/CS gene locus.

PMID- 9259316
TI  - Synthetic glucocorticoids that dissociate transactivation and AP-1
      transrepression exhibit antiinflammatory activity in vivo.
AB  - Some of the most potent antiinflammatory and immunosuppressive agents are
      synthetic glucocorticoids. However, major side effects severely limit their
      therapeutic use. The development of improved glucocorticoid-based drugs will
      require the separation of beneficial from deleterious effects. One possibility
      toward this goal is to try to dissociate two main activities of glucocorticoids,
      i.e. transactivation and transrepression. Screening of a library of compounds
      using transactivation and AP-1 transrepression models in transiently transfected
      cells identified dissociated glucocorticoids, which exert strong AP-1 inhibition
      but little or no transactivation. Importantly, despite high ligand binding
      affinity, the prototypic dissociated compound, RU24858, acted as a weak agonist
      and did not efficiently antagonize dexamethasone-induced transcription in
      transfected cells. Similar results were obtained in hepatic HTC cells for the
      transactivation of the endogenous tyrosine amino transferase gene (TAT), which
      encodes one of the enzymes involved in the glucocorticoid-dependent stimulation
      of neoglucogenesis. To investigate whether dissociated glucocorticoids retained
      the antiinflammatory and immunosuppressive potential of classic glucocorticoids,
      several in vitro and in vivo models were used. Indeed, secretion of the
      proinflammatory lymphokine interleukin-1beta was severely inhibited by
      dissociated glucocorticoids in human monocytic THP 1 cells. Moreover, in two in
      vivo models, these compounds exerted an antiinflammatory and immunosuppressive
      activity as potent as that of the classic glucocorticoid prednisolone. These
      results may lead to an improvement of antiinflammatory and immunosuppressive
      therapies and provide a novel concept for drug discovery.

PMID- 9259318
TI  - Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors:
      evidence for selective sorting of receptor and ligand.
AB  - Angiotensin II (Ang II) binds to two different receptor subtypes, AT1 and AT2
      receptors. In many cases, receptor stimulation by Ang II is followed by a rapid
      desensitization of the intracellular signal transduction and a decrease in cell
      surface receptor number. The present study was designed to examine by
      immunofluorescence microscopy the cellular trafficking pathways of Ang II and its
      AT1a and AT2 receptors in human embryonal kidney 293 cells stably expressing
      these receptor subtypes. Fluorescently labeled Ang II and AT1a receptors were
      rapidly internalized into endosomes. AT2 receptors were localized in the plasma
      membrane and did not undergo endocytosis upon agonist stimulation. After removal
      of agonist, AT1a receptors recycled to the plasma membrane, whereas fluorescently
      labeled Ang II was targeted to the lysosomal pathway. Even though no further loss
      of surface receptor was measurable by ligand binding at steady state, fluorescein
      Ang II was continuously internalized, and cycling of receptor between endosomal
      vesicles and the plasma membrane was detected by antibody feeding. These
      experiments provide evidence for subtype-specific receptor sorting and
      internalization of Ang II and its AT1a receptor as a receptor-ligand complex, and
      they suggest that the sequestration of receptors into endosomes is in dynamic
      equilibrium with receptor cycling to the plasma membrane. Finally,
      internalization of AT1a receptors and Ang II persists after desensitization
      mechanisms have attenuated Ca2+ and inositol 1,4,5-trisphosphate signaling.

PMID- 9259317
TI  - A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and
      androgen-regulated expression of the endogenous prostate-specific antigen gene in
      humans.
AB  - Prostate-specific antigen (PSA) is a kallikrein-like serine protease, which is
      almost exclusively synthesized in the luminal epithelial cells of the human
      prostate. PSA expression is androgen regulated. Previously, we characterized in
      vitro the proximal promoter, and a strong enhancer region, approximately 4 kb
      upstream of the PSA gene. Both regions are needed for high, androgen-regulated
      activity of the PSA promoter in LNCaP cells. The goal of the present study is the
      in vivo characterization of the PSA promoter. Three transgenic mouse lines
      carrying the Escherichia coli LacZ gene, driven by the 632-bp proximal PSA
      promoter, and three lines with LacZ, driven by the 6-kb PSA promoter, were
      generated. Expression of the LacZ reporter gene was analyzed in a large series of
      tissues. Transgene expression could not be demonstrated in any of the transgenic
      animals carrying the proximal PSA promoter. All three lines carrying the 6-kb PSA
      promoter showed lateral prostate-specific beta-galactosidase activity. Transgene
      expression was undetectable until 8 weeks after birth. Upon castration, beta
      galactosidase activity rapidly declined. It could be restored by subsequent
      androgen administration. A search for mouse PSA-related kallikrein genes
      expressed in the prostate led to the identification of mGK22, which was
      previously demonstrated to be expressed in the submandibular salivary gland.
      Therefore, the 6-kb PSA-LacZ transgene followed the expression pattern of the PSA
      gene in humans, which is almost completely prostate-specific, rather than that of
      mGK22 in mice. In conclusion, the 6-kb promoter fragment appears to contain most,
      if not all, information for androgen regulation and prostate specificity of the
      PSA gene.

PMID- 9259319
TI  - Identification of transcripts initiated from an internal promoter in the c-erbA
      alpha locus that encode inhibitors of retinoic acid receptor-alpha and
      triiodothyronine receptor activities.
AB  - The thyroid hormone receptor-coding locus, c-erbA alpha, generates several mRNAs
      originating from a single primary transcript that undergoes alternative splicing.
      We have identified for the first time two new transcripts, called TRdelta alpha1
      and TRdelta alpha2 [mRNA for isoform alpha1 and alpha2 of the T3 receptor (TR),
      respectively], whose transcription is initiated from an internal promoter located
      within intron 7 of the c-erbA alpha gene. These two new transcripts exhibit
      tissue-specific patterns of expression in the mouse. These two patterns are in
      sharp contrast with the expression patterns of the full-length transcripts
      generated from the c-erbA alpha locus. TR alpha1 and TRdelta alpha2 mRNAs encode
      N-terminally truncated isoforms of T3R alpha1 and T3R alpha2, respectively. The
      protein product of TRdelta alpha1 antagonizes the transcriptional activation
      elicited by T3 and retinoic acid. This protein inhibits the ligand-induced
      activating functions of T3R alpha1 and 9-cis-retinoic acid receptor-alpha but
      does not affect the retinoic acid-dependent activating function of retinoic acid
      receptor-alpha. We predict that these truncated proteins may work as down
      regulators of transcriptional activity of nuclear hormone receptors in vivo.

PMID- 9259320
TI  - Identification and characterization of single strand DNA-binding protein that
      represses growth hormone receptor gene expression.
AB  - The GH receptor is essential for the actions of GH on growth and metabolism.
      Electromobility shift assay established that a 42-bp enhancer element in the
      promoter of the L1 transcript of the murine GH receptor bound nuclear proteins
      specific for the coding strand or the DNA duplex. Using methylation interference
      footprinting and electromobility shift assay with mutant oligonucleotides, the
      DNA-binding sites for the single-strand DNA-binding protein (SSBP) and the double
      strand DNA-binding protein (DSBP) were mapped and shown to be contiguous with
      partial overlap. Shift-Western analysis indicated that the SSBP was a component
      of the DSBP complex. A functional interaction between SSBP and DSBP was suggested
      by the effect of the exclusion of SSBP on equilibrium binding and dissociation
      rate ("off rate") of the DSBP-DNA complex. Experiments using the anionic
      detergent deoxycholate provided evidence for a direct protein-protein interaction
      between SSBP and DSBP. Using lectin-affinity chromatography, discordance between
      the pattern of O-glycosylation of SSBP and DSBP was demonstrated. Transient
      transfection experiments support the role of SSBP as a repressor of DSBP's
      activation of transcription of the GH receptor gene. Southwestern analysis
      indicated that a protein of molecular mass 23-kDa exhibited binding activity
      specific to the coding strand of the enhancer element. We conclude that single-
      and double-strand DNA-binding proteins conjointly regulate the expression of the
      murine GH receptor gene.

PMID- 9259321
TI  - Inhibition of gonadotropin-releasing hormone receptor signaling by expression of
      a splice variant of the human receptor.
AB  - GnRH binds to a specific G protein-coupled receptor in the pituitary to regulate
      synthesis and secretion of gonadotropins. Using RT-PCR and human pituitary
      poly(A)+ RNA as a template, the full-length GnRH receptor (wild type) and a
      second truncated cDNA characterized by a 128-bp deletion between nucleotide
      positions 522 and 651 were cloned. The deletion causes a frame shift in the open
      reading frame, thus generating new coding sequence for further 75 amino acids.
      The truncated cDNA arises from alternative splicing by accepting a cryptic
      splicing acceptor site in exon 2. Distinct translation products of approximately
      45-50 and 42 kDa were immunoprecipitated from COS-7 cells transfected with cDNA
      coding for wild type GnRH receptor and the truncated splice variant,
      respectively. Immunocytochemical and enzyme-linked immunosorbent assay studies
      revealed a membranous expression pattern for both receptor isoforms. Expression
      of the splice variant, however, occurred at a significantly lower cell surface
      receptor density. In terms of ligand binding and phospholipase C activation, the
      wild type receptor showed characteristics of a typical GnRH receptor, whereas the
      splice variant was incapable of ligand binding and signal transduction.
      Coexpression of wild type and truncated proteins in transiently or stably
      transfected cells, however, resulted in impaired signaling via the wild type
      receptor by reducing maximal agonist-induced inositol phosphate accumulation. The
      inhibitory effect depended on the amount of splice variant cDNA cotransfected and
      was specific for the GnRH receptor because signaling via other G(q/11)-coupled
      receptors, such as the thromboxane A2, M5 muscarinic, and V1 vasopressin
      receptors, was not affected. Immunological studies revealed that coexpression of
      the wild type receptor and the truncated splice variant resulted in impaired
      insertion of the wild type receptor into the plasma membrane. Thus, expression of
      truncated receptor proteins may highlight a novel principle of specific
      functional inhibition of G protein-coupled receptors.

PMID- 9259322
TI  - Human estrogen receptor (ER) gene promoter-P1: estradiol-independent activity and
      estradiol inducibility in ER+ and ER- cells.
AB  - Estrogen receptor (ER) is expressed at a low level in normal tissues such as
      breast and uterus but at a high level in breast and endometrial carcinomas. A
      proximal element (ERF-1) located between positions +133 and +204 relative to the
      promoter P1 major initiation site has been recently identified in ER+ cells and
      contributes to the differential promoter activity between ER+ and ER- cells. In
      this study, MCF7 and HeLa cells were transfected with chloramphenicol
      acetyltransferase constructs containing ER gene promoter P1 sequences. We show
      here that the sequences lying between nucleotides +13 to +212 are also essential
      for transcription at the ER gene promoter P1 in ER- cells, which do not express
      ERF-1. Interestingly, on gel shift experiments, a complex specific to ER- cells
      forms in the region spanning nucleotides +123 to +210. We also show that promoter
      P1 is responsive to estradiol in cells expressing endogenous (MCF7) or exogenous
      ER. We further demonstrate, using mutational analysis and gel retardation assays,
      that the three half-estrogen response elements located between nucleotides -420
      and -892 are responsible for the estradiol inducibility of promoter P1. Because
      estradiol has a mitogenic effect on both breast and endometrial epithelial cells,
      our data would give an insight into the role of estrogens in the occurrence of
      breast and endometrial carcinomas.

PMID- 9259323
TI  - Activities in Pit-1 determine whether receptor interacting protein 140 activates
      or inhibits Pit-1/nuclear receptor transcriptional synergy.
AB  - Pituitary-specific transcription of the evolutionarily related rat (r) GH and PRL
      genes involves synergistic interactions between Pit-1 and other promoter-binding
      factors including nuclear receptors. We show that Pit-1/thyroid hormone receptor
      (TR) and Pit-1/estrogen receptor (ER) synergistic activation of the rGH and rPRL
      promoters are globally similar. Both synergies depend upon the same activation
      functions in Pit-1 and also require activation function-2 conserved in TR and ER.
      The activation function-2 binding protein, RIP140, previously thought to be a
      nuclear receptor coactivator, strongly inhibits both Pit-1/TR and Pit-1/ER
      synergy. RIP140 inhibition is profoundly influenced, in a promoter-specific
      fashion, by a synergism-selective function in Pit-1: deletion of Pit-1 amino
      acids 72-100 switches RIP140 to an activator of Pit-1/ER and Pit-1/TR synergy at
      the rPRL promoter but not at the rGH promoter. Pit-1 amino acids 101-125 are
      required for RIP140 inhibition or activation again only at the rPRL promoter.
      Therefore, functions within one factor can determine the activity of a
      coactivator binding to its synergistic partner. This promoter context-specific
      synergistic interplay between transcription factors and coactivators is likely an
      essential determinant of cell-specific transcriptional regulation.

PMID- 9259324
TI  - Molecular cloning of TA16, a transcriptional repressor that may mediate
      glucocorticoid-induced growth arrest of leiomyosarcoma cells.
AB  - The DDT1 MF2 smooth muscle tumor cell line was derived from an estrogen/androgen
      induced leiomyosarcoma that arose in the ductus deferens of a Syrian hamster. The
      growth of this cell line is arrested at the G0/G1 phase of the cell cycle after
      treatment with glucocorticoids. To identify the putative gene(s) that are
      potentially involved in this hormone-induced cell growth arrest, we have used a
      differential screening technique to clone those genes whose expression is induced
      or up-regulated by glucocorticoids. A number of glucocorticoid response genes
      were thereby isolated from the leiomyosarcoma cells. One of these clones, termed
      TA16, was found to be markedly up-regulated by glucocorticoids in DDT1 MF2 cells,
      but only marginally changed in GR1 cells, a glucocorticoid-resistant variant that
      was selected from the wild type DDT1 MF2 cell. Isolation and sequencing of its
      intact cDNA indicated that the TA16 encodes a protein 485 amino acids long, and
      its sequence is closely homologous to a novel transcriptional repressor that
      presumably represses the transcription activity of some zinc finger
      transcriptional factors through a direct interaction. Transfection assays
      demonstrated that introduction of an antisense TA16 cDNA expression vector,
      controlled by an MMTV promoter, into the DDT1 MF2 cell significantly relieved the
      glucocorticoid-induced cell growth arrest. This finding suggests that TA16 might
      participate in the mediation of glucocorticoid-induced cell cycle arrest in
      leiomyosarcoma cells.

PMID- 9259325
TI  - Multiple prolactin (PRL) receptor cytoplasmic residues and Stat1 mediate PRL
      signaling to the interferon regulatory factor-1 promoter.
AB  - The Nb2 PRL receptor (PRL-R) is known to mediate PRL signaling to the interferon
      (IFN) regulatory factor-1 (IRF-1) gene via the family of signal transducers and
      activators of transcription or Stats. To analyze the components of the PRL
      R/Stat/IRF-1 signaling pathway, various PRL-R, Stat, and IRF-1-CAT reporter
      constructs were transiently cotransfected into COS cells. First, mutations in the
      IFNgamma-activated sequence (GAS), either multimerized or in the context of the
      1.7-kb IRF-1 promoter, failed to mediate a PRL response, showing that the IRF-1
      GAS is a target of PRL signaling. Next, pairwise alanine substitutions into
      conserved residues in the proline-rich motif or Box 1 region and two tyrosine
      mutations, Y308F and Y382F, in the PRL-R intracellular domain all impaired PRL
      signaling to multimerized GAS or to the 1.7-kb IRF-1 promoter. Furthermore, these
      PRL-R mutants mediated reduced Stat1 binding to the IRF-1 GAS. Transfection of
      Stat1 further enhanced PRL signaling to the IRF-1 promoter, suggesting that Stat1
      is a positive mediator of PRL action. These studies show that both membrane
      proximal and distal residues of the PRL-R are involved in signaling to the IRF-1
      gene. Further, Stat1 and the GAS element are important for PRL activation of the
      IRF-1 gene.

PMID- 9259326
TI  - Overexpression of unliganded steroid receptors activates endogenous heat shock
      factor.
AB  - The synthesis of a number of heat shock proteins is induced in response to
      various environmental stresses. The resultant induction of heat shock protein
      gene transcription is brought about by the activation of specific transcription
      factors termed heat shock factors (HSFs) that exist in a latent form in
      nonstressed cells. Multiple mechanisms are likely to contribute to negative
      regulation of HSF activity. One model, which remains controversial, proposes the
      existence of a negative feedback loop by which one of the products of HSF
      activation, the 70-kDa heat shock protein (hsp70), acts as one of its negative
      regulators. Accordingly, HSF activation would proceed upon sequestration of hsp70
      by substrates (i.e. unfolded proteins) that may accumulate to relatively high
      levels in stressed cells. To examine whether putative native substrates of hsp70
      (e.g. steroid receptors) could impact the regulation of HSF activity, we have
      examined whether steroid receptors could activate endogenous HSF. We have found
      that overexpression of androgen (AR), glucocorticoid (GR), mineralocorticoid, and
      progesterone receptors in transiently transfected COS-1 cells induced HSF
      activity. With the exception of AR, which was competent to activate HSF when
      either liganded or unliganded, all other steroid receptors tested only activated
      HSF when unliganded. This activity was mapped to the ligand-binding domain of rat
      GR, making it unlikely that HSF activation results from the induction of a novel
      gene product by unliganded receptors. As overexpression of hsp70 can eliminate
      HSF activation by AR, GR, and progesterone receptors, we favor the view that HSF
      activation can result from the sequestration, by steroid receptor ligand-binding
      domains, of a negative regulator of HSF, such as hsp70 or an hsp70-associated
      protein.

PMID- 9259327
TI  - Mechanistic aspects of estrogen receptor activation probed with constitutively
      active estrogen receptors: correlations with DNA and coregulator interactions and
      receptor conformational changes.
AB  - The estrogen receptor (ER) belongs to a large family of nuclear receptors, many
      of whose members function as ligand-dependent transcriptional activators. The
      mechanism by which the receptor is converted from an inactive into an activated
      state is not yet completely understood. To investigate the kind of changes in
      receptor conformation and interactions that are involved in this activation, we
      have used the wild type ER and a set of constitutively active ER point mutants
      that show from 20% to nearly 100% activity in the absence of estrogen. These
      mutants are of particular interest as they could mimic, in the absence of ligand,
      the activated state of the wild type receptor. We have analyzed several
      transcriptional steps that could be involved in the activation: the ability of
      these receptors 1) to interact with several coactivators (steroid receptor
      coactivator-1, SRC-1; transcription intermediary factor-1, TIF-1; and estrogen
      receptor-associated protein 140, ERAP 140) and with members of the preinitiation
      complex [TATA box-binding protein (TBP), transcription factor IIB (TFIIB)]; 2) to
      exhibit conformational changes revealed by proteolytic digest patterns similar to
      those observed for the wild type hormone-occupied ER; and 3) to bend estrogen
      response element-containing DNA, which is thought to be one of the important
      phenomena triggering transcriptional activation. Our results demonstrate that the
      interaction of these mutant receptors with coactivators is likely to be one of
      the features of the activated step, as the mutant receptors interacted with some
      coactivators in a ligand-independent manner in proportion to their extent of
      constitutive activity. However, the different degrees of ligand-independent
      interaction of the mutant ERs with the three coactivators suggest that SRC-1, TIF
      1, and ERAP 140 may play different roles in receptor activity. Limited
      proteolytic digest experiments reveal that the activated state of the receptor
      corresponds to a particular conformation of the receptor, which is fully observed
      with the mutant ER showing the highest activity in the absence of estrogen.
      Finally, it appears that in inactive or active states, the receptor exhibits
      distinctly different DNA-bending abilities. Addition of estradiol is able to
      modify the bending ability of only the wild type receptor, whereas estradiol has
      no influence on the constitutive receptors, which exhibited the same bending
      ability as that observed for the ligand-occupied wild type receptor. These data
      document that the ER undergoes major changes in its conformation and also in its
      functional properties when it is turned from an inactive into an active state and
      that mutational changes in the ER protein that result in constitutive, hormone
      independent activation mimic many of the changes in ER properties that are
      normally under hormone regulation.

PMID- 9259329
TI  - Pulmonary Artery Catheter Consensus Conference: consensus statement.

PMID- 9259328
TI  - DNA sequences and their binding proteins required for Sertoli cell-specific
      transcription of the rat androgen-binding protein gene.
AB  - The rat androgen-binding protein (ABP) gene is transcriptionally regulated from
      two promoters: the P1 promoter regulates expression of transcripts starting at
      exon 1, whereas P(A) regulates transcripts containing exon A. The P1 promoter
      directs cell-specific gene regulation of ABP secreted by Sertoli cells. In this
      study, the Sertoli cell-regulatory sequences of P1 were further examined using a
      luciferase reporter system with three cell lines, including a Sertoli cell line
      (MSC-1) that expresses the ABP gene. Deletion mapping experiments determined that
      the sequences required for full activity in MSC-1 cells were included within 619
      bp of the start site and identified several regions that demonstrated increased
      luciferase activity: the -583 bp to -564 bp, -503 bp to -484 bp, and -114 bp to 
      65 regions. The activities contributed by each region were much higher (up to 120
      fold) in MSC-1 cells than in MA10 Leydig or NIH3T3 fibroblast cells. Nuclear
      binding proteins and their binding sequences were identified using several
      molecular biology techniques. Complexes formed by nuclear proteins of MSC-1,
      MA10, and NIH3T3 cells, which bind specifically to the -114 to -65-bp region,
      were identified using gel retardation assays. Furthermore, the inverted repeat
      sequence in this region, 5'-AGGGTCAGTGTCCCT-3' was identified by
      deoxyribonuclease (DNase) I footprinting. The regulatory element contained within
      the -503 to -484-bp region was identified by scanning mutagenesis, but no protein
      was found that bound to this sequence by gel retardation or DNase I protection
      assays. This element is characterized by the core sequence, 5'-GGAGGC-3'. The
      third regulatory region (residues -583 to -564) bound a protein complex that
      retarded mobility of the free DNA probe in a gel shift assay. Using several
      techniques, the binding sequence was identified as 5'-TTCATAGTATCCATTAAAC-3'. In
      summary, these data have identified several transcriptional regulatory sequences
      and their binding proteins, which appear to play a role in the Sertoli cell
      specific expression of the ABP gene.

PMID- 9259330
TI  - Right heart catheterization: is it effective?
AB  - OBJECTIVES: To discuss the advantages of different methods of determining the
      effectiveness of healthcare interventions, to evaluate the basis for the
      assumption that right heart catheterization is effective, and to consider how
      right heart catheterization may fail to improve outcomes in some circumstances.
      DATA SOURCE: Published English language literature on right heart catheterization
      and patient outcomes. DISCUSSION: We recently reported an association between the
      use of right heart catheterization in the initial care of critically ill patients
      and increased risk of death. This finding is troubling and warrants future study.
      In this article I address the role of randomized controlled trials and
      observational studies in the evaluation of the effectiveness of healthcare
      interventions. I discuss the basis in the published literature for assuming that
      right heart catheterization improves outcomes. Finally I present a variety of
      problems with right heart catheterization which might allow this procedure, which
      logically should help patients, to fail to achieve a beneficial effect for some
      patients. CONCLUSION: We must do appropriate prospective studies to determine who
      benefits from right heart catheterization and who does not. We owe our patients
      nothing less.

PMID- 9259331
TI  - Physicians' attitudes toward and knowledge of the pulmonary artery catheter:
      Society of Critical Care Medicine membership survey.
AB  - OBJECTIVE: To survey physicians' attitudes toward the pulmonary artery catheter
      (PAC) and to assess physicians' knowledge of pulmonary artery catheterization.
      DESIGN: Mail survey/examination. PARTICIPANTS: Physician members of the Society
      of Critical Care Medicine in the United States. METHODS: A 51-question two-part
      survey was mailed to U.S. Society of Critical Care Medicine physician members by
      an independent research firm. The participants were instructed to answer the
      questions unassisted and to return the survey within one month. The first 20
      questions surveyed physicians' attitudes toward the PAC. The remaining 31
      multiple-choice questions tested the physicians' knowledge of the PAC and its
      use. The multiple-choice questions were obtained from a previous study which
      assessed physicians' knowledge of pulmonary artery catheterization. RESULTS: Five
      thousand surveys were mailed in October of 1996; 1095 surveys were returned in
      November of 1996, yielding a 22% return rate. The survey results were significant
      in that 95% of the respondents felt that a moratorium against PAC use was not
      warranted and that 75% of the respondents favored a prospective, randomized,
      controlled trial involving pulmonary artery catheterization. The mean test score
      for the multiple-choice questions was 25.6 (82.6%) with a standard deviation of
      +/- 3.46 and a range of 3 to 31 (10%-100%). The mean score was found to be
      significantly associated (p <0.001) with the following variables: specialty,
      practice pattern, number of PAC insertions performed per month, and whether or
      not the physician was trained and/or certified in critical care medicine. One
      third of respondents incorrectly identified the pulmonary artery occlusion
      pressure on a clear tracing and could not identify the major components of oxygen
      transport. CONCLUSION: The results of this mail survey/examination reflect the
      current attitudes and knowledge of the responding U.S. physician members of the
      Society of Critical Care Medicine regarding the PAC. The majority of the
      respondents are in favor of a prospective, randomized, controlled trial involving
      the PAC; 95% of the respondents feel that a moratorium on further use of the PAC
      is currently not warranted. Rather than a call for such a moratorium, a call for
      the development and maintenance of educational, credentialing, and continuous
      quality improvement policies involving the PAC is warranted and overdue.

PMID- 9259333
TI  - Pulmonary artery catheters and outcome in the perioperative period.
AB  - OBJECTIVE: To review the literature addressing use of the pulmonary artery
      catheter (PAC) in the perioperative patient. DATA SOURCE: All pertinent English
      language articles dealing with the use of pulmonary artery catheterization in
      perioperative patients were retrieved from 1977 through 1996. STUDY SELECTION:
      Articles were chosen if the perioperative use of pulmonary artery catheterization
      was studied or reviewed. DATA EXTRACTION: From the articles selected, information
      was obtained about changes in therapy and changes in outcome associated with PAC
      use in patients undergoing cardiac surgery, aortic surgery, peripheral vascular
      surgery, and neurosurgery. Information was also extracted about perioperative PAC
      use in geriatric patients and in patients with preeclampsia. DATA SYNTHESIS: Low
      risk patients undergoing cardiac surgery do not appear to benefit from PAC use.
      Studies looking at high-risk patients undergoing cardiac surgery are lacking,
      making accurate determination of patient benefit difficult. The PAC may be useful
      in the management of some patients undergoing aortic surgery, though recent
      studies have identified populations of patients that can be safely monitored by
      less invasive means. Use of the PAC may lead to fewer complications in high-risk
      patients undergoing peripheral vascular surgery. Until data are forthcoming, it
      is not possible to accurately assess the overall impact of PAC use on
      complications and mortality in patients undergoing neurosurgical procedures.
      However, use of the PAC to monitor and treat air embolism in this group of
      patients does not appear to be appropriate. Routine perioperative use of the PAC
      does not appear to be appropriate because of age alone. Available scientific data
      do not support use of the PAC in patients with uncomplicated preeclampsia;
      however, some experts feel that PAC use may be helpful in the management of
      selected patients with severe preeclampsia. CONCLUSION: There are no Grade A
      indications for PAC use in the perioperative period. Current available literature
      suffers from a lack of randomized controlled clinical trials. Multicentered
      randomized controlled trials are needed.

PMID- 9259332
TI  - Pulmonary artery catheters in cardiovascular disease.
AB  - OBJECTIVE: To review the literature addressing the use of the pulmonary artery
      catheter (PAC) in patients with cardiovascular disease. DATA SOURCE: All
      pertinent English language articles dealing with pulmonary artery catheterization
      in patients with cardiovascular disease were retrieved from 1976 through 1996.
      STUDY SELECTION: Articles were chosen for review if the use of pulmonary artery
      catheterization in patients with cardiovascular disease was studied or reviewed.
      DATA EXTRACTION: From the articles selected, information was obtained about
      changes in therapy and changes in outcome associated with PAC use in patients
      with cardiovascular disease. DATA SYNTHESIS: Whether enhanced understanding of
      patient hemodynamics translates into definable benefits for those patients has
      recently come into question. Although there are a number of conventional clinical
      indications for pulmonary artery catheterization, and several studies have shown
      that catheterization prompts changes in therapy in many patients, most data
      regarding outcomes are retrospective; prospective randomized trials are lacking.
      Nonetheless, we believe, based on the available evidence and the preponderance of
      expert opinion, that management with the PAC improves outcome in several patient
      populations. These populations include: a) patients with acute myocardial
      infarction either complicated by cardiogenic shock or progressive hypotension, or
      associated with mechanical complications; b) patients with congestive heart
      failure refractory to empiric therapy; c) patients with pulmonary hypertension;
      and d) patients with shock or hemodynamic instability. CONCLUSION: Pulmonary
      artery catheterization is often used to optimize patient management, although
      this may not be demonstrable in terms of prospective trials using mortality or
      other "hard" outcome measures. Nonetheless, more rapid diagnosis and achievement
      of therapeutic endpoints guided by PAC use can decrease morbidity and intensive
      care days.

PMID- 9259334
TI  - Do pulmonary artery catheters alter outcome in trauma patients?
AB  - OBJECTIVE: To review the literature addressing the use of the pulmonary artery
      catheter (PAC) in victims of blunt and penetrating trauma and examine the
      available evidence that supports or refutes the claim that PAC use alters outcome
      in this patient population. Furthermore, to determine what additional research
      should be done in this area. DATA SOURCE: All pertinent English language articles
      dealing with pulmonary artery catheterization in trauma patients were retrieved
      from 1979 through 1996. STUDY SELECTION: Clinical studies were considered if PACs
      were used to establish a cardiopulmonary diagnosis, optimize or achieve endpoints
      of oxygen transport and utilization indices, or guide and/or determine response
      to therapy. Emphasis was placed on prospective, randomized, controlled trials.
      However, descriptive case series and retrospectively-analyzed, uncontrolled
      reviews comprise the majority of available literature. DATA EXTRACTION: From
      these selective studies, information was obtained regarding patient demographics,
      therapeutic endpoints, and achieved outcome. DATA SYNTHESIS: Insufficient
      evidence exists to support a true survival benefit. However, recommendations for
      indications can be proposed where a reduction in morbidity or improvement in
      functional outcome is suggested. CONCLUSION: Hemodynamic data obtained from the
      PAC appear to be beneficial for the following indications: a) to ascertain the
      status of underlying cardiovascular performance and/or the need for improvement;
      b) to direct therapy when noninvasive monitoring may be inadequate, misleading,
      or the endpoints of resuscitation difficult to define; c) to assess response to
      resuscitation; d) to potentially decrease secondary injury when severe closed
      head or acute spinal cord injuries are components of multisystem trauma; e) to
      augment clinical decision-making when major trauma is complicated by severe adult
      respiratory distress syndrome, progressive oliguria/anuria, myocardial ischemia,
      congestive heart failure, or major thermal injury; and f) to establish futility
      of care.

PMID- 9259335
TI  - Pulmonary artery catheters in sepsis/septic shock.
AB  - OBJECTIVE: To review the literature addressing use of the pulmonary artery
      catheter (PAC) in patients with sepsis and septic shock. DATA SOURCE: All
      pertinent English language articles dealing with the use of pulmonary artery
      catheterization in patients with sepsis and septic shock were retrieved from 1984
      through 1996. STUDY SELECTION: Articles were chosen for review if the use of
      pulmonary artery catheterization in patients with sepsis/septic shock was studied
      or reviewed. DATA EXTRACTION: From the articles selected, information was
      obtained about changes in therapy and changes in outcome associated with PAC use
      in patients with sepsis/septic shock. DATA SYNTHESIS: Inadequate evidence exists
      to accurately determine if PAC use improves outcome in patients with
      sepsis/septic shock. Attempting to achieve supranormal hemodynamic variables in
      patients with septic shock is not warranted. CONCLUSION: Based largely upon
      expert opinion, PAC use may be appropriate in patients with septic shock
      unresponsive to early resuscitative measures. Maintenance of normal hemodynamics
      in this group of patients appears to be the appropriate goal. Research is needed
      to determine the proper role of the PAC in patients with sepsis/septic shock.

PMID- 9259336
TI  - Supranormal oxygen delivery in critical illness.
AB  - OBJECTIVE: To review the literature addressing use of the pulmonary artery
      catheter (PAC) to augment oxygen delivery to supranormal levels in critical
      illness. DATA SOURCE: All pertinent English language articles dealing with use of
      the PAC to augment oxygen delivery to supranormal levels in critical illness were
      retrieved from 1988 through 1996. STUDY SELECTION: Articles were chosen if
      material relevant to supranormal oxygen delivery in critically ill patients was
      studied or reviewed. DATA EXTRACTION: Methodology of the available studies was
      analyzed. From the articles selected, information was obtained regarding changes
      in outcome associated with prospective goal-oriented hemodynamic intervention
      using a PAC to augment systemic oxygen delivery to supranormal levels prior to
      high-risk surgery. Patient outcome information was also obtained regarding use of
      the PAC to augment oxygen delivery to supranormal values begun after the onset of
      the systemic inflammatory response syndrome (SIRS) following sepsis or trauma.
      DATA SYNTHESIS: Inadequate evidence exists to accurately determine if PAC use to
      augment systemic oxygen delivery improves outcome in either of these
      circumstances. CONCLUSION: Further research must be performed before a
      recommendation can be made about goal-oriented hemodynamic intervention utilizing
      the PAC to augment oxygen delivery to supranormal levels prior to high-risk
      surgery. PAC-guided hemodynamic intervention to augment oxygen delivery to
      supranormal values in patients with SIRS-related organ dysfunction from sepsis,
      trauma, or postoperative complications is not recommended at this time. Carefully
      designed, multicenter, randomized, controlled trials are needed to establish
      whether augmenting oxygen delivery improves organ-specific outcomes and survival
      under each of these circumstances.

PMID- 9259337
TI  - Right heart catheterization in acute respiratory failure.
AB  - OBJECTIVE: To review the literature addressing the use of the pulmonary artery
      catheter (PAC) in patients with respiratory failure. DATA SOURCE: All pertinent
      English language articles dealing with pulmonary artery catheterization in
      patients with respiratory failure were retrieved from 1983 through 1996. STUDY
      SELECTION: Articles were chosen for review if the use of pulmonary artery
      catheterization in patients with respiratory failure was studied or reviewed.
      DATA EXTRACTION: From the articles selected, information was obtained about
      changes in therapy and changes in outcome associated with PAC use in patients
      with respiratory failure. DATA SYNTHESIS: Evidence exists to suggest that use of
      the PAC in patients with respiratory failure often results in a change in
      diagnosis and therapy. Inadequate evidence exists to accurately determine benefit
      or harm from PAC use in patients with respiratory failure. CONCLUSION: The
      optimal role of the PAC as a diagnostic and monitoring device in different types
      of respiratory failure has not been clearly defined. Research is needed to
      determine the role of the PAC in very carefully defined groups of patients with
      respiratory failure.

PMID- 9259339
TI  - The new pulmonary artery catheters: continuous venous oximetry, right ventricular
      ejection fraction, and continuous cardiac output.
AB  - OBJECTIVE: To review the literature addressing the new pulmonary artery
      catheters: continuous venous oximetry, right ventricular ejection fraction, and
      continuous cardiac output. DATA SOURCE: All pertinent English language literature
      dealing with new pulmonary artery catheters were retrieved from 1981 through
      1996. STUDY SELECTION: Articles were chosen for review if the primary objective
      of the paper was study or review of technology related to new pulmonary artery
      catheters. DATA EXTRACTION: From the literature selected, information was
      obtained about continuous venous oximetry, right ventricular ejection fraction,
      and continuous cardiac output catheters. DATA SYNTHESIS: When pulmonary artery
      catheterization is used, continuous venous oximetry catheters may be considered
      for use when it is anticipated that therapy will be based upon oxygen transport
      end points. When pulmonary artery catheterization is used, right ventricular
      ejection fraction catheters may be considered for use when the anticipated
      therapy will be based upon evaluation of ventricular preload and when central
      venous pressure and/or pulmonary artery occlusion do not accurately reflect
      preload. When pulmonary artery catheterization is used, continuous cardiac output
      catheters may be considered for use in titration of interventions employed to
      alter stroke volume. CONCLUSION: Clinician misinterpretation and misapplication
      of the data appear to be the greatest impediment to using pulmonary artery
      catheterization to alter pathophysiologic processes and improve outcome in
      critically ill patients. Future research should first document effectiveness or
      lack of effectiveness of the "standard" pulmonary artery catheter (PAC). Pending
      these results, outcome and cost/benefit studies should be performed comparing
      "standard" with new PACs.

PMID- 9259338
TI  - Pulmonary artery catheterization in children.
AB  - OBJECTIVE: To review the literature addressing use of the pulmonary artery
      catheter (PAC) in pediatric patients. DATA SOURCE: All pertinent English language
      articles dealing with the use of pulmonary artery catheterization in pediatric
      patients were retrieved from 1979 through 1996. STUDY SELECTION: Articles were
      chosen for review if the use of pulmonary artery catheterization in pediatric
      patients was studied or reviewed. DATA EXTRACTION: From the articles selected,
      information was obtained about changes in diagnosis, therapy and outcome
      associated with PAC use in pediatric patients. DATA SYNTHESIS: The available
      literature suggests substantial value from the information made available by use
      of the PAC in a small group of critically ill infants and children. CONCLUSION:
      Until there is substantive evidence in children that outcome is negatively
      affected by their use, PACs should remain available. Experienced physicians
      should directly supervise PAC insertion and use.

PMID- 9259340
TI  - Complications associated with pulmonary artery catheterization.
AB  - OBJECTIVE: To review the literature addressing complications associated with
      pulmonary artery catheterization. DATA SOURCE: All pertinent English language
      articles dealing with complications associated with pulmonary artery
      catheterization were retrieved from 1979 through 1996. STUDY SELECTION: Articles
      were chosen for review if the primary objective of the paper was complications
      associated with pulmonary artery catheterization. DATA EXTRACTION: From the
      literature selected, information was obtained about frequency and types of
      complications associated with pulmonary artery catheterization. DATA SYNTHESIS:
      Complications are grouped into three categories: complications associated with
      insertion, complications associated with indwelling catheters, and complications
      that occur during or after removal of the catheter. CONCLUSION: With the
      introduction of any new technology, there are risks and potential complications.
      Pulmonary artery catheterization was introduced in 1970 and has not been without
      complications and controversy. Recent research findings have again led to the
      discussion of the efficacy and safety of pulmonary artery catheter (PAC) use.
      This article discusses complications associated with pulmonary artery
      catheterization and makes recommendations for future research and continued safe
      use of the PAC.

PMID- 9259341
TI  - Ethical issues of clinical trials for the pulmonary artery catheter.
AB  - OBJECTIVE: To review the literature addressing ethical issues related to clinical
      research and the pulmonary artery catheter (PAC). DATA SOURCE: All pertinent
      English language articles dealing with ethical issues related to clinical
      research and the PAC were retrieved from 1970 through 1996. STUDY SELECTION:
      Articles were chosen for review if ethical issues related to clinical research
      and the PAC were studied or reviewed. DATA EXTRACTION: From the articles
      selected, information was obtained about the ethics of clinical research related
      to the PAC. DATA SYNTHESIS: Many current procedures and treatments used on a
      daily basis have not been proven effective by clinical trials. Studies showing
      increased mortality with the use of PACs are worrisome. Many clinicians have
      strong preferences about the use of PACs for various indications and there have
      been difficulties performing clinical trials. Clinical equipoise occurs when
      competent physicians are content to have their patients receive any of the
      various treatments in a randomized trial because, based on available data, none
      has proven preferable. Clinical equipoise for pulmonary artery catheterization
      for various indications is unknown. If >70% of experts determine that pulmonary
      artery catheterization is indicated or contraindicated for specific indications,
      clinical equipoise does not exist and a trial could not ethically be performed
      for these indications. Indications and contraindications for pulmonary artery
      catheterization for these indications, however, should be determined. Clinical
      equipoise would be present if <70% of experts favor pulmonary artery
      catheterization for a specific indication and trials could be performed in
      patients with these disorders. CONCLUSION: Randomized clinical trails of
      pulmonary artery catheterization can ethically be conducted.

PMID- 9259342
TI  - Pulmonary artery catheterization: a narrative and systematic critique of
      randomized controlled trials and recommendations for the future.
AB  - OBJECTIVE: The purpose of this review is to evaluate the current literature
      regarding the efficacy of pulmonary artery catheterization, to assess the quality
      of existing randomized controlled trials and to make recommendations for future
      studies. DATA SOURCE: A Medline search was conducted of English language studies
      published between 1970 and 1996 using as search terms "Swan-Ganz
      catheterization," "pulmonary artery catheterization," and "right heart
      catheterization." STUDY SELECTION: Randomized controlled trials of pulmonary
      artery catheterization were selected for review. Sixteen randomized controlled
      trials were identified. DATA EXTRACTION: The quality of the randomized controlled
      trials was assessed and a formal meta-analysis was performed. DATA SYNTHESIS: The
      overall quality score was 40.15 +/- 6.32 out of a possible score of 100. Serious
      deficiencies were identified including a lack of a priori sample size
      calculations, unclear definitions of concomitant therapy, inability to blind
      physicians and patients, and lack of blinded outcome assessments. A random
      effects model found the relative risk ratio of .808 (95% confidence interval [CI]
      = .598, 1.091; p = .148). An analysis of potential covariates revealed patients
      from surgical series treated with pulmonary artery catheter (PAC)-guided therapy
      had a relative risk ratio of .578 (95% CI = .357, .937; p = .03) compared with
      control groups. Patients from medical or mixed unit series had a relative risk of
      1.043 (95% CI = .784, 1.387; p = NS). CONCLUSION: Existing randomized controlled
      trials on PAC-guided strategies reveal a modest risk reduction that does reach
      statistical significance. Risk reduction appears to be greatest in surgical
      series. Deficiencies of these trials have important implications for the proper
      design of future trials.

PMID- 9259343
TI  - The issue of a U.S. Food and Drug Administration moratorium on the use of the
      pulmonary artery catheter.
AB  - OBJECTIVE: To review the literature addressing the issue of a U.S. Food and Drug
      Administration (FDA) moratorium on use of the pulmonary artery catheter (PAC).
      DATA SOURCE: Pertinent English language articles dealing with medical devices
      including the PAC were retrieved from 1976 through 1996. STUDY SELECTION:
      Articles were chosen if issues related to medical devices were studied or
      reviewed. DATA EXTRACTION: From the articles selected, information about the 1976
      Medical Device Amendment and the PAC was obtained. DATA SYNTHESIS: In 1976, the
      Medical Device Amendment gave the FDA power over medical devices. The pulmonary
      artery catheter is considered a class II device and was on the market before
      passage of the 1976 Act. Class II devices require general and specific controls
      to reasonably assure safety and effectiveness. A reasonable assurance of safety
      occurs when the probable benefits to health from the use of the device outweigh
      any probable risks. If a monitor measures an established and well-understood
      variable and the intended use claim is limited to the measurement of that
      variable, then the effectiveness consists of determining device safety and
      performance defined as the measurement of agreement with a recognized reference
      method. Deaths and serious injuries secondary to pulmonary artery catheterization
      are extremely rare despite more than 25 years of use. Pulmonary artery catheter
      manufacturer's indications for use are measurements such as hemodynamic
      pressures, thermodilution cardiac output, continuous cardiac output, mixed venous
      oxygen saturation, and blood sampling; intended uses have not included claims of
      clinical benefit. Evidence exists that pulmonary artery catheterization provides
      agreement with established measurements including pressure and cardiac output.
      Evidence also exists that pulmonary artery catheter derived data are unobtainable
      clinically, that the derived data helps in therapy changes and may lead to more
      appropriate therapy. The evidence demonstrates an absence of unreasonable risk of
      injury from pulmonary artery catheterization and provision of important clinical
      results. Therefore, pulmonary artery catheterization meets FDA requirements for
      safety and effectiveness. CONCLUSION: An FDA moratorium on the use of the PAC is
      not indicated.

PMID- 9259344
TI  - Is nursing education adequate for pulmonary artery catheter utilization?
AB  - OBJECTIVE: To review the literature addressing the nursing education of pulmonary
      artery catheterization. DATA SOURCE: All pertinent English language articles
      dealing with nursing education and pulmonary artery catheterization were
      retrieved from 1983 through 1996. STUDY SELECTION: Clinical studies related to
      nursing education in this field were selected. Only two studies addressing
      nursing knowledge of pulmonary artery catheterization have been published to
      date. DATA EXTRACTION: Both studies suggest that an improvement in several areas
      of nursing knowledge is necessary. Unfortunately, these studies are limited in
      scope and depth. DATA SYNTHESIS: The adequacy of nursing education in hemodynamic
      monitoring, ranging from cognitive to technical issues, has not been addressed in
      a systematic fashion in the literature. CONCLUSION: Nurses need a standardized
      hemodynamic monitoring curriculum. At present, education of nurses is primarily
      institutionally based. While national guidelines exist for hemodynamic
      monitoring, no mechanisms are in place to verify the skills of individual nurses.
      Since physicians depend on the knowledge and skill of the bedside nurse to obtain
      accurate information, any study evaluating the impact of pulmonary artery
      catheterization should first control for nursing knowledge. Since this
      information is not currently known, the precise impact of pulmonary artery
      catheterization cannot be assessed at this time.

PMID- 9259345
TI  - Training requirements for pulmonary artery catheter utilization in adult
      patients.
AB  - OBJECTIVE: To review the literature addressing the issue of training requirements
      for pulmonary artery catheter (PAC) utilization in adult patients. DATA SOURCE:
      All pertinent English language articles dealing with training requirements for
      pulmonary artery catheterization were retrieved from 1984 through 1997. STUDY
      SELECTION: Articles were chosen if issues related to training and pulmonary
      artery catheterization were studied or reviewed. DATA EXTRACTION: From the
      articles selected, information about PAC training was obtained. DATA SYNTHESIS:
      The PAC is a commonly employed monitoring tool in the management of critically
      ill patients. Recent publications have strongly implied that PAC monitoring is
      associated with an increased morbidity and no notable clinical benefit. In
      response to these findings, the value of PAC monitoring has been questioned. The
      benefit assessment of any technology on clinical outcome presumes that the care
      provider possesses the skills and knowledge to optimally utilize the data
      obtained and simultaneously minimize the potential complications. Several recent
      articles have addressed physician and nurse knowledge as it pertains to PAC
      monitoring. The results of these studies are quite alarming. Marked deficiencies
      of knowledge were noted particularly in area of data interpretation and patient
      management. Extrapolating from their conclusions, it appears that any effort to
      proactively assess the value of PAC monitoring will be compromised until attempts
      are made to standardize and optimize the clinical skills of those involved in
      utilization of the technology. This article provides a proposed program for
      clinical education and raises the question regarding the necessity of
      demonstrated proficiency. CONCLUSION: Training, credentialing, and continued
      quality improvement related to PAC should be improved.

PMID- 9259346
TI  - The pulmonary artery catheter: economic aspects.
AB  - OBJECTIVE: To review the literature addressing economic issues related to use of
      the pulmonary artery catheter (PAC). DATA SOURCE: All pertinent English language
      articles related to economic analysis of the use of pulmonary artery
      catheterization were retrieved from 1977 through 1996. STUDY SELECTION: Articles
      were chosen for review if an economic analysis related to use of the PAC was
      studied or reviewed. DATA EXTRACTION: From the articles selected, information was
      obtained about economic aspects related to pulmonary artery catheterization. DATA
      SYNTHESIS: Inadequate evidence exists to accurately determine if PAC use is truly
      cost-effective. CONCLUSION: Widespread use of the PAC has significant economic
      ramifications. Data regarding cost-effectiveness of the PAC is extremely limited
      in terms of methodology and scope. Economic impact and cost-effectiveness are
      moot prior to establishing clinical efficacy.

PMID- 9259347
TI  - Expression of the conjugate export pump encoded by the mrp2 gene in the apical
      membrane of kidney proximal tubules.
AB  - A novel ATP-dependent export pump for amphiphilic anionic conjugates, which has
      been cloned recently from liver, was identified in rat kidney and localized to
      the apical membrane domain of proximal tubule epithelia. This 190-kD membrane
      glycoprotein (Mrp2) has been described previously as the hepatocyte canalicular
      isoform of the multidrug resistance protein and as the canalicular multispecific
      organic anion transporter. Mrp2 was identified in kidney by reverse transcription
      PCR followed by sequencing of the amplified 786-bp fragment and by
      immunoblotting, using an antibody specifically reacting with the carboxy terminus
      of rat Mrp2. Double immunofluorescence and confocal laser-scanning microscopy
      showed the presence of Mrp2 in the brush-border membrane domain of segments S1,
      S2, and S3 of proximal tubule epithelia. Mrp2 was not detectable in other
      segments of the nephron. The onset of Mrp2 expression during development occurred
      in a very early stage of nephron development. Mrp2 represents the first cloned
      ATP-dependent export pump for amphiphilic organic anions identified in kidney and
      localized to the apical membrane domain of proximal tubule epithelia. Mrp2 may
      contribute to cellular detoxification and to the secretion of endogenous and
      xenobiotic anionic substances, most of which are conjugates, from the blood into
      urine.

PMID- 9259348
TI  - Organic anion secretion in polycystic kidney disease.
AB  - This study examined whether organic anion secretion contributes to fluid
      accumulation in cysts in polycystic kidney disease. Clearance and micropuncture
      studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD
      cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats
      manifest a slowly progressive autosomal dominant polycystic kidney disease that
      closely resembles the human disorder. Left kidney GFR (polyfructosan clearance),
      in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats
      and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH)
      secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy
      rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no
      significant differences in GFR or the maximal rate of PAH secretion despite the
      presence of cystic disease. Using fluorescence microscopy, it was found that 27
      of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by
      the PAH system. Transmission electron micrographs of superficial cysts that had
      secreted sulfonefluorescein demonstrated the presence of both normal-appearing
      and poorly differentiated proximal tubule cells. Segments of superficial proximal
      convoluted tubules or cysts, isolated by upstream and downstream wax blocks,
      failed to accumulate fluid when PAH was infused intravenously. With the
      stationary microperfusion technique, PAH secretion by both normal and cystic
      nephrons was demonstrated. It is concluded that most proximal cystic epithelia
      retain the ability to secrete organic anions. Secretion of organic anions,
      however, does not appear to contribute in any substantial way to fluid
      accumulation in cysts in the rat kidney.

PMID- 9259349
TI  - Reflex influences on renal nerve activity characteristics in nephrosis and heart
      failure.
AB  - Cardiac baroreflex regulation of efferent renal sympathetic nerve activity
      (ERSNA) is abnormal in nephrotic syndrome (NS). The purpose of the present study
      was to examine the responses of amplitude and frequency of synchronized ERSNA
      discharge in anesthetized NS rats subjected to reflex maneuvers that alter the
      activity of and the interaction between aortic and cardiac baroreceptors. Steady
      state ERSNA was analyzed in three groups of anesthetized rats: control, NS, and
      congestive heart failure (CHF) (in the latter, the defect in cardiac baroreflex
      regulation of ERSNA is peripheral rather than central). In protocol A, analysis
      was performed during control, after bilateral aortic depressor nerve section,
      after bilateral cervical vagus nerve section, and during central vagus nerve
      stimulation (VAGSTIM). In protocol B, analysis was performed during control,
      after bilateral cervical vagus nerve section, after bilateral aortic depressor
      nerve section, and during central aortic depressor nerve stimulation. In protocol
      A, VAGSTIM decreased ERSNA and peak height (fewer active fibers), but not peak
      frequency, in control and CHF but not NS rats. In NS rats, this lack of effect of
      VAGSTIM was specific for ERSNA, because depressor and bradycardia responses to
      VAGSTIM were unaffected. In protocol B, central aortic depressor nerve
      stimulation decreased ERSNA and peak height, but not peak frequency, in control,
      CHF, and NS rats similarly. It is concluded that the defect in cardiac baroreflex
      function in NS is specific for ERSNA, is central rather than peripheral, and
      affects the number of active renal sympathetic nerve fibers rather than their
      firing frequency.

PMID- 9259350
TI  - Sex hormones and renal nitric oxide synthases.
AB  - The present study was undertaken to determine whether sex hormones influence
      nitric oxide synthase levels in the kidney. Five groups of rats were studied:
      males, castrated males, females, oophorectomized females, and oophorectomized
      females receiving estradiol replacement therapy. Endothelial nitric oxide
      synthase (eNOS) levels in the kidney were measured by Western blotting. eNOS
      levels were significantly greater in the renal medulla of female rats compared
      with male rats (3545 +/- 473 versus 2418 +/- 205 densitometry units (DU), P <
      0.05). Oophorectomy reduced renal medullary eNOS levels to that of intact male
      rats (2566 +/- 304 DU, P = NS). Estrogen replacement therapy significantly
      increased medullary eNOS levels in oophorectomized animals (3249 +/- 377 versus
      2302 +/- 213 DU, P < 0.05). Renal inducible nitric oxide synthase (iNOS) levels
      were measured after induction with lipopolysaccharide. iNOS levels were
      significantly greater in the renal medulla of female rats compared with male rats
      (677 +/- 253 versus 252 +/- 12 DU, P < 0.05). Oophorectomy reduced renal
      medullary iNOS levels to that of intact male rats (295 +/- 57 DU, P = NS). In
      contrast, estrogen replacement therapy significantly increased medullary iNOS
      levels in oophorectomized animals (682 +/- 356 versus 160 +/- 92 DU, P < 0.05).
      Steady-state levels of mRNA for iNOS were found to be higher in the inner medulla
      of female rats compared with male rats (1519 +/- 211 versus 899 +/- 105 DU, P <
      0.05). In contrast to these findings, sex hormones failed to influence nitric
      oxide production or iNOS levels in lipopolysaccharide-stimulated mesangial cells
      in culture. These results suggest that gender may influence renal medullary
      synthesis of nitric oxide.

PMID- 9259351
TI  - HDL causes mesangial cell mitogenesis through a tyrosine kinase-dependent
      receptor mechanism.
AB  - Hypercholesterolemia and mesangial cell proliferation have been proposed to play
      a role in the progression of glomerulosclerosis in diabetic nephropathy and other
      renal diseases. Although LDL is mitogenic for and cytotoxic to mesangial cells,
      the effect of HDL on these cells is unknown. HDL stimulates fibroblast
      mitogenesis and is the principal cholesterol-bearing lipoprotein in the rat, the
      experimental model for studying the effect of hyperlipidemia on renal disease.
      Insulin is mitogenic in several cell systems, and its levels are increased in
      serum in non-insulin-dependent diabetes mellitus. This study investigates whether
      HDL acts as a growth factor in mesangial cells and whether it functions in
      parallel with insulin. It was found that HDL at protein concentrations between 10
      and 500 microg/ml, both alone and in the presence of 100 nM insulin, increased
      DNA synthesis in mesangial cells (129 to 165% of control for HDL alone; 140 to
      235% for HDL plus insulin), whereas HDL at 1000 microg/ml and greater inhibited
      mesangial cell proliferation. Insulin alone at 100 nM stimulated [3H]thymidine
      incorporation in the same cell system (145% of control); the mitogenic effect of
      insulin was additive to that of HDL. Purified apo A-I had a similar effect, but
      at significantly lower concentrations. Specific binding of HDL to mesangial cells
      was demonstrated (B(max) [binding constant] of 5.19 +/- 0.70 x 10(-7) micromol of
      HDL bound/mg cell protein and K(b) of 2.83 +/- 0.22 nM). Tetranitromethane alters
      apo A-I, preventing binding to its cognate receptor. Tetranitromethane-modified
      HDL did not bind to mesangial cells and had no effect on [3H]thymidine
      incorporation. Addition of HDL to mesangial cells caused an immediate transient
      increase in free intracellular calcium in several representative mesangial cells,
      similar to the response seen with platelet-derived growth factor. The mitogenic
      effect of HDL was not altered after attenuation of cellular protein kinase C
      activity, but the stimulatory effect of HDL alone and in combination with insulin
      on DNA synthesis was completely eliminated after inhibition of cellular tyrosine
      kinases by 24-h pretreatment with 0.25 microM herbimycin A. Thus, HDL binds to a
      specific apo A-I-dependent receptor, promotes DNA synthesis, and initiates second
      messenger events by a tyrosine kinase-dependent and protein kinase C-independent
      mechanism.

PMID- 9259352
TI  - Antigen-antibody complexes enhance the production of complement component C3 by
      human mesangial cells.
AB  - Deposition of immune complexes (ICX), with or without complement, occurs in
      various forms of glomerulonephritis. It has been reported that upregulation of
      complement C3 mRNA expression is found in kidneys of patients with ICX
      glomerulonephritis. In vitro studies have indicated that mesangial cells (MC)
      synthesize C3. Furthermore, MC express Fc gammaRIII receptors. This study
      investigates whether ICX alter C3 and factor H production by MC. MC were cultured
      in medium alone or in medium with insoluble heat-aggregated rat IgG (AIgG) or
      with insoluble ICX. Basal production of C3 and factor H was 10 +/- 1 ng/10(6) and
      605 +/- 15 ng/10(6) cells, respectively. The presence of 400 microg/ml AIgG or
      ICX resulted in upregulation of C3 production to 999 +/- 15 ng/10(6) and 510 +/-
      1 ng/10(6) cells, respectively, whereas no significant change in factor H
      production was observed. The upregulation of C3 was inhibitable by cycloheximide,
      suggesting that de novo protein synthesis was required. By reverse transcription
      PCR and Northern blot analysis, it was demonstrated that C3 and interleukin-6
      mRNA expression was upregulated in MC after incubation with AIgG. No detectable
      change in factor H mRNA expression was seen. In conclusion, it is shown that
      incubation of MC with AIgG or ICX not only results in upregulated production of
      inflammatory mediators such as cytokines, but also leads to an upregulation of C3
      synthesis. Therefore, it is hypothesized that ICX deposited within the mesangium
      may enhance the local production of C3 via interaction with Fc receptors on MC.

PMID- 9259353
TI  - Platelet-activating factor stimulates gene expression and synthesis of matrix
      proteins in cultured rat and human mesangial cells: role of TGF-beta.
AB  - Platelet-activating factor (PAF) is a potent inflammatory mediator that
      participates in the pathogenesis of proteinuria and glomerular damage. However,
      the role of this lipid in glomerular sclerosis remains unknown. This study
      examines the effect of PAF on the regulation of extracellular matrix proteins by
      rat and human mesangial cells. PAF increased in a dose-dependent manner the gene
      expression of fibronectin and type IV collagen, but not type I collagen.
      Moreover, an increase in cell-associated and soluble fibronectin synthesis was
      also seen. These effects were abolished by BN52021 and WEB2086, two different PAF
      receptor antagonists. Because transforming growth factor (TGF)-beta has been
      considered a profibrogenic cytokine, this study also evaluated whether PAF
      effects might be mediated by the production of endogenous TGF-beta. PAF caused an
      increase in TGF-beta1 mRNA expression (by a protein kinase C-dependent pathway)
      and TGF-beta activity. Moreover, PAF-induced fibronectin synthesis was totally
      abolished when an anti-TGF-beta-neutralizing antibody was added to the culture
      medium, suggesting that PAF stimulates fibronectin synthesis, at least in part,
      through the induction of TGF-beta. Addition of cycloheximide, a protein synthesis
      inhibitor, upregulated PAF-induced fibronectin mRNA expression but downregulated
      PAF-induced TGF-beta1 gene expression, suggesting the existence of different
      regulatory transcriptional factors of the two proteins. These results suggest
      that PAF may be implicated in matrix accumulation during renal injury and
      therefore contribute to the pathogenesis of glomerulosclerosis.

PMID- 9259354
TI  - High glucose inhibits nitric oxide production in cultured rat mesangial cells.
AB  - Hyperglycemia directly contributes to the development of diabetic nephropathy. A
      high-serum glucose concentration alters intraglomerular hemodynamics and promotes
      deposition of extracellular matrix in the kidney. Nitric oxide (NO) is a short
      lived messenger molecule that participates in the regulation of renal blood flow,
      GFR, and mesangial matrix accumulation. Therefore, in this study it was tested
      whether high glucose directly modulates NO synthesis by rat mesangial cells in
      vitro by measuring the accumulation of nitrite, the stable metabolite of NO, in
      the incubation media. Raising the external glucose concentration to 33.3 mM for
      24 to 72 h reduced nitrite levels in cell supernatants in a time-dependent manner
      to a nadir of 14 +/- 3% of the amount in normal glucose media (5.6 mM) (P <
      0.01). The decline in NO synthesis in high glucose media was paralleled by
      decreased cyclic guanosine monophosphate generation; however, there was no
      alteration in rat mesangial cell expression of inducible NO synthase protein. The
      suppressive effect of high glucose on NO production by mesangial cells was not
      modified by inhibition of protein kinase C (H-7), the addition of antioxidants
      (vitamin E or superoxide dismutase), or a pan-specific anti-transforming growth
      factor-beta antibody. An elevated ambient glucose caused a time-dependent
      reduction in mesangial cell L-arginine content. Addition of L-arginine (10 to 20
      mM) to external media partially reversed the inhibitory effect of high glucose on
      mesangial cell NO production in a dose-dependent manner. The highest dose of L
      arginine (20 mM) increased mesangial cell L-arginine content to comparable levels
      in normal and high glucose media. These results indicate that high glucose causes
      depletion of L-arginine in mesangial cells and compromises NO synthesis.
      Limitation in the metabolic precursor and other, as yet unidentified, factors act
      to reduce NO production by mesangial cells in the presence of an elevated ambient
      glucose level, a change that may play a role in the development of diabetic
      glomerulosclerosis.

PMID- 9259355
TI  - Aggravation of polycystic kidney disease in Han:SPRD rats by buthionine
      sulfoximine.
AB  - The administration of ammonium chloride or of sodium or potassium bicarbonate has
      marked effects on the development of polycystic kidney disease (PKD) in Han:SPRD
      rats. Because of the possibility that these effects are mediated by changes in
      redox metabolism, the aim of this study was to determine whether depletion of
      glutathione, the most abundant and important cellular thiol and scavenger of
      reactive oxygen species, would affect the development of PKD in this animal
      model. +/+ and cy/+ Han:SPRD rats were treated with: (1) L-buthionine(S,R)
      sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, the
      rate-limiting enzyme for the synthesis of glutathione; (2) glutathione monoethyl
      ester (GME), a compound that is known to increase the intracellular levels of
      glutathione; or (3) BSO and GME. Treatment with these drugs was started at 3 wk
      of age, and the animals were killed at 6 or 8 wk of age. Renal levels of oxidized
      glutathione were significantly higher in cy/+ than in +/+ rats, whereas no
      significant differences in reduced glutathione were detected. The administration
      of BSO caused a marked reduction in the levels of glutathione. The administration
      of GME caused a significant increase in the levels of glutathione at 2 h, but not
      at 12 h, after the administration. The increase in the renal levels of
      glutathione 2 h after the administration of GME was less in the rats treated with
      BSO than in the rats not receiving this drug, indicating that in part the
      increase in glutathione level was due to de novo synthesis. BSO-induced
      glutathione depletion was accompanied by a marked aggravation of the renal cystic
      disease, as reflected by kidney weights, histological scores, and plasma urea
      concentrations. However, the administration of GME did not lessen the cystic
      disease and did not reverse the effects of BSO. The transient effect of GME
      administration and the simultaneous increases in the levels of cysteine and
      oxidized glutathione, in addition to reduced glutathione, may explain the lack of
      protection by GME. These data support the notion that changes in redox metabolism
      may affect the development of PKD.

PMID- 9259356
TI  - Left ventricular hypertrophy in autosomal dominant polycystic kidney disease.
AB  - Cardiovascular complications are the most common cause of morbidity and mortality
      in patients with autosomal dominant polycystic kidney disease (ADPKD). To
      understand this relationship, known cardiovascular risk factors were examined in
      ADPKD. Left ventricular hypertrophy (LVH) is a known, important risk factor for
      premature cardiovascular death in patients with essential hypertension.
      Hypertension is known to occur frequently and early in ADPKD patients. The
      frequency of LVH in ADPKD patients and its relation with hypertension and other
      risk factors, however, is not known. In this study, echocardiographic tests were
      performed in 116 consecutive adult ADPKD patients and 77 healthy control
      subjects. There was a significantly higher frequency of LVH in ADPKD men (46
      versus 20%, P < 0.05) and women (37 versus 12%, P < 0.005) compared with control
      subjects. LVH in ADPKD patients was associated with higher systolic and diastolic
      arterial BP. There also was an association between LVH, diminished renal
      function, and increased renal volume. When comparing ADPKD patients with and
      without LVH, the former were older, weighed more, had a higher prevalence of
      hypertension, and had a lower hematocrit value and more renal impairment. LVH was
      also present in 23% of normotensive ADPKD patients and 16% of healthy control
      subjects (P = NS), but did not correlate with BP. The role of BP as a
      contributing factor to LVH in ADPKD patients may be due in part to earlier onset
      and inadequate treatment.

PMID- 9259357
TI  - Intracranial arterial dolichoectasia in autosomal dominant polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder with
      a variety of cardiovascular manifestations. This study presents a group of
      patients with ADPKD who had intracranial arterial dolichoectasia. One hundred
      seventy-eight ADPKD patients were screened with magnetic resonance angiography,
      40 ADPKD patients had conventional angiography, and 98 ADPKD patients underwent a
      brain autopsy. For comparison, 360 patients without ADPKD who had magnetic
      resonance angiography and conventional angiography or brain autopsy were also
      studied. The prevalence of asymptomatic intracranial arterial dolichoectasia was
      2.2% (4 of 178), 2.5% (1 of 40), and 2.0% (2 of 98) in the three ADPKD groups,
      respectively. None of the patients without ADPKD had intracranial arterial
      dolichoectasia. In addition to the seven patients with asymptomatic disease, two
      ADPKD patients with vertebrobasilar dolichoectasia had posterior circulation
      ischemic symptoms. The mean age of the nine patients (five men and four women)
      was 56.6 yr (range, 41 to 67 yr). The posterior circulation was involved in five
      patients, the anterior circulation was involved in two patients, and both were
      involved in two patients. Arterial dissection was believed to have caused middle
      cerebral artery dolichoectasia in one patient, and intracranial arterial
      dissections were strongly suspected in two other patients. Six of the nine
      patients with intracranial arterial dolichoectasia had additional vascular
      manifestations of ADPKD. Some patients with ADPKD are at an increased risk of
      developing intracranial arterial dolichoectasia and dissections. Recognizing this
      association is important because (1) it may be a cause of stroke; (2) it may
      mimic a saccular aneurysm on radiographic studies; and (3) it suggests that the
      arteriopathy of ADPKD may be more generalized than previously believed.

PMID- 9259358
TI  - Impact of increasing dialysis volume on adequacy targets: a prospective study.
AB  - Failure to achieve target values for both urea (Kt/V) and creatinine clearance
      has been associated with increased morbidity and mortality in continuous
      ambulatory peritoneal dialysis patients. The conventional continuous ambulatory
      peritoneal dialysis regimen, which uses four 2-L exchanges per day, has resulted
      in up to 40% of such patients failing to achieve proposed targets for weekly Kt/V
      of 1.7 and weekly creatinine clearance (WCC) of 50 L. In a prospective study, the
      impact of increasing prescribed volumes by 0.5 L per exchange was evaluated on
      attaining urea and creatinine clearance targets over a 1-yr period. At 1 yr, 17
      patients remaining on the increased dialysis prescription were compared with 18
      patients remaining on an unchanged regimen. The mean increase in daily prescribed
      volume was 1.5 L (22%). This resulted in a significant increase in both
      peritoneal dialysis Kt/V (1.59 to 1.78 L = 12%) and peritoneal dialysis WCC (45.8
      to 50.1 L = 10%) by 1 yr. Because of loss of renal function, there was no
      significant increase in total clearance at 1 yr, but this loss of renal clearance
      was offset by the gain in peritoneal clearance. Residual renal function fell at a
      similar rate in both the increased dialysis and control groups. In the latter,
      although peritoneal clearance remained stable over the 1-yr period, loss of renal
      function resulted in reductions in both total Kt/V and WCC. In conclusion,
      exchange volume can be increased to compensate for loss of renal function over a
      1-yr period. Progressive loss of renal clearance resulted in only a modest gain
      in total solute clearance. It was the larger patients who tolerated the increase
      in exchange volumes. However, such patients (by virtue of their size) tended not
      to achieve target values for solute clearance, and the modest gain in peritoneal
      clearance was insufficient to increase the number of patients in this group
      achieving such targets for dialysis adequacy.

PMID- 9259360
TI  - Impaired delivery of hemodialysis prescriptions: an analysis of causes and an
      approach to evaluation.
AB  - Serial kinetic modeling is commonly used in hemodialysis to assess the adequacy
      of dialysis. A variety of problems lead to declining Kt/V in previously stable
      patients. These include noncompliance, vascular access recirculation, and
      dialyzer dysfunction. The purpose of this study was to find the relative
      frequencies of these problems in a group of patients undergoing routine
      hemodialysis. Simultaneous urea kinetic modeling and access recirculation were
      tested during 3 consecutive months. The baseline Kt/V was defined as the average
      of each patient's Kt/V values obtained during the previous 4 mo. A clinically
      important fall in Kt/V was defined as a decline of > or =0.2 if the baseline Kt/V
      was > or =1.2, or a decline of > or =0.1 if the baseline Kt/V was <1.2. Ninety
      three of 375 (25%) sessions met the criteria for a significant decline in urea
      kinetic modeling. The baseline Kt/V in this group was 1.33 +/- 0.20 (mean +/-
      SEM) and declined to 1.02 +/- 0.18 in the abnormal month (P < 0.05). In 42% of
      instances with a decline of Kt/V, reduced blood processing due to a lower blood
      flow or shorter time than prescribed was responsible. Recirculation of >12% was
      found in 25% of sessions with a decrease in Kt/V. These patients most often had
      access dysfunction or reversed needles. The remaining one-third of patients with
      decreases in Kt/V had no problem identified, and subsequent monthly kinetic
      modeling results returned to baseline. These results suggest that analysis of
      falling urea kinetic modeling results should include a careful review of the
      dialysis record for reductions in prescribed time or blood flow rates followed by
      vascular access testing. If these evaluations are unrevealing, urea kinetic
      modeling results usually return to baseline in the next month.

PMID- 9259359
TI  - Commonly prescribed salt intake in continuous ambulatory peritoneal dialysis
      patients is too restrictive: results of a double-blind crossover study.
AB  - Salt restriction in continuous ambulatory peritoneal dialysis (CAPD) patients is
      widely prescribed and thereby may reduce quality of life. It is presumed that
      this has a beneficial effect on BP and reduces the need for hypertonic dialysate.
      However, this has never been formally evaluated. A double-blind crossover study
      of placebo versus sodium chloride pills (60 mEq of sodium per day) is presented
      in 20 stable CAPD patients, 10 of whom were hypertensive. Dietary sodium was
      quantified throughout the study by 3-d dietary histories and remained unaltered
      throughout. There was a clinically unimportant but statistically significant rise
      in BP with added salt: 135/77 to 144/82 (P < 0.05). No rise in BP occurred in the
      hypertensive patients. Weights, use of hypertonic dialysate, and BP medications
      remained unaltered throughout the study. In conclusion, 200 mEq of sodium per
      day, i.e., a normal sodium intake, is easily tolerated in stable CAPD patients,
      and the recommended sodium intake commonly prescribed is too restrictive.

PMID- 9259361
TI  - Angiotensin-converting enzyme genotype and renal allograft survival.
AB  - Increased activity of the renin-angiotensin system has been implicated in
      decreased, long-term survival of renal allografts. Recent studies suggest that a
      deletion variant of the angiotensin-converting enzyme, associated with increased
      humoral and tissue activity of this enzyme, is a risk factor for the development
      of diabetic nephropathy and the progression of IgA nephropathy. To determine
      whether the deletion variant of the angiotensin-converting enzyme gene influences
      the long-term outcome in renal transplant recipients, the relationship between
      donor and recipient angiotensin-converting enzyme genotype and clinical outcome
      were examined over a follow-up period up to 30 mo in a cohort of 269 Caucasian
      patients undergoing kidney transplantation between 1988 and 1993. In a subsequent
      case control study, the frequencies of the angiotensin-converting enzyme genotype
      were compared in a group of Caucasian patients with a graft survival of less than
      3 yr (mean survival, 11 mo; n = 328) with the frequencies in patients with a
      graft survival of at least 3 yr (mean survival, 65 mo, n = 461). Neither in the
      cohort nor in the case control study was there a significant effect of recipient
      or donor angiotensin-converting enzyme genotype on transplant survival.
      Furthermore, the frequency of the angiotensin-converting enzyme deletion allele
      both in recipients and donors was similar to that reported in Caucasian controls.
      This study, therefore, does not support the hypothesis that the recipient or
      donor angiotensin-converting enzyme insertion/deletion polymorphism is an
      important determinant of transplant survival in Caucasian patients undergoing
      renal transplantation.

PMID- 9259362
TI  - Immunoglobulin A nephropathy: a clinical perspective.

PMID- 9259363
TI  - Familial hypothalamic diabetes insipidus in rats (Brattleboro strain). 1964.

PMID- 9259364
TI  - Risk of fatal cerebrovascular accident in patients on peritoneal dialysis versus
      hemodialysis.
AB  - Several reports have suggested that the incidence of hemorrhagic stroke may be
      greater on hemodialysis as compared with that among the general population and
      that patients with intracranial hemorrhage should be treated with peritoneal
      dialysis rather than hemodialysis. However, whether the risk of fatal stroke is
      greater on hemodialysis versus peritoneal dialysis has not been systematically
      examined. In this study, the case of a diabetic patient with extensive peripheral
      vascular disease who, after 7 years on hemodialysis, was changed to peritoneal
      dialysis and subsequently suffered two strokes over a 5-month period, is
      reported. Recent data from the United States Renal Data System, which allow a
      comparison of death rates from stroke in large numbers of hemodialysis versus
      peritoneal dialysis patients, are reviewed. These data suggest that the risk of
      death from stroke may actually be greater for patients on peritoneal dialysis
      versus hemodialysis in spite of their having a lesser prevalence of preexisting
      cerebrovascular disease. This risk was greatest for elderly diabetic black
      patients and women, who experienced a nearly twofold-greater odds favoring death
      from stroke on peritoneal dialysis versus hemodialysis. Selection of a dialysis
      modality for a patient beginning renal replacement therapy may require the
      consideration of such data, particularly in those patients with extensive
      preexisting vascular disease.

PMID- 9259365
TI  - Acute renal failure due to lymphomatous infiltration of the kidneys.
AB  - Acute renal failure (ARF) is an unusual manifestation of lymphomatous
      infiltration of the kidneys. In this article, a patient whose initial
      presentation of lymphoma was the sudden onset of painless hematuria and ARF is
      described. The absence of other causes of ARF, together with massively enlarged
      unobstructed kidneys on renal ultrasonography, strongly suggested an infiltrative
      process. Renal biopsy established the diagnosis of non-Hodgkin's lymphoma. Pulse
      steroid therapy was associated with rapid improvement of renal function and
      kidney size, but a moderate degree of tumor lysis syndrome ensued. Further
      recovery followed with chemotherapy. Whereas widespread infiltration of the
      kidneys is present in almost one third of patients with lymphoma at autopsy, this
      rarely causes clinical symptoms. Nevertheless, because it often responds to
      therapy, lymphomatous infiltration should be suspected in any patient presenting
      with unexplained ARF and enlarged kidneys, especially in the setting of
      widespread lymphoma.

PMID- 9259366
TI  - Fifty years of the Nuremberg Code: a time for retrospection and introspection.

PMID- 9259367
TI  - Lack of association between bipolar disorder and tyrosine hydroxylase: a meta
      analysis.
AB  - Tyrosine hydroxylase (TH) is a candidate gene extensively explored in several
      association studies of bipolar disorder (BD). However, because of conflicting
      results of independent studies and low statistical power of individual studies to
      detect small differences between cases and controls, reliable conclusions are
      difficult to formulate. A method to obtain more reliable conclusions about the
      involvement of the TH locus in the etiology of BD is meta-analysis. We undertook
      a meta-analysis of studies that investigated the association between BD and TH
      genetic markers. The studies were identified by means of computerized searches of
      several databases, and the scanning of review articles and the reference lists of
      the primary articles identified. More than 60 publications were reviewed, and 9
      relevant articles were included in this meta-analysis, with an overall sample of
      1,069 subjects (547 cases and 522 normal controls). The overall odds ratio (and
      confidence interval) based on combining the results of the studies was 1.02 (0.68
      1.54). Test of the null hypothesis that the mean log odds ratio equals zero (chi2
      = 0.11; 5 df; P > 0.05) indicated that there was no overall association between
      bipolar disorder and tyrosine hydroxylase.

PMID- 9259368
TI  - Schizophrenia in the genetic isolate of Finland.
AB  - We compared the features of schizophrenia in the homogeneous population of
      Finland (population about 5,000,000) and in an internal isolate in northeastern
      Finland inhabited in the 1680s by a small group of founders (current population
      about 18,000) in a register-based epidemiological study. We identified all cases
      with a diagnosis of schizophrenia in Finland born between 1940-1969 using three
      national computerized registers and found a total of 267 schizophrenia patients
      in the internal isolate and 29,124 in Finland. The lifetime prevalence was 2.21%
      in the internal isolate and 1.21% in Finland, respectively. The age-corrected
      lifetime risk was 3.2% in the internal isolate and 1.1% in the whole country. The
      risk of schizophrenia to siblings in the internal isolate was 6.4% (95%
      confidence interval 0.052, 0.078), 9.1% (95% CI 0.062, 0.130), and 6.8% (95% CI
      0.028, 0.135) given 1, 2, or 3 affected siblings, and for all Finland 4.2% (95%
      CI 0.036, 0.043), 6.4% (95% CI 0.058, 0.071), and 8.7% (95% CI 0.068, 0.107)
      given 1, 2, or 3, affected siblings, respectively. The mean number of children in
      schizophrenia families and thus the number of families having at least two
      affected individuals were clearly higher in the isolate (24.9% vs 9.2%). We did
      not find any other epidemiological features differing between these two regions.
      It seems that the family material collected from the internal isolate is a
      representative subsample from the entire country and hopefully it enables easier
      identification of at least some predisposing genes for schizophrenia due to its
      unique population structure.

PMID- 9259369
TI  - No evidence for a schizophrenia susceptibility gene in the vicinity of IL2RB on
      chromosome 22.
AB  - Pulver et al. [1994a] reported modest linkage evidence for a dominantly (D)
      inherited "schizophrenia gene" in the vicinity of IL2RB on chromosome 22q12, and
      Coon et al. [1994] adduced moderate evidence under a recessive (R) model. We
      report here a replication study to test the hypothesis that one of these two
      models (or a third, intermediate (I) model) adequately describes the co
      segregation of schizophrenia and chromosome 22q12 markers in an independent
      sample of 23 multiplex families. Altogether nine transmission models were
      evaluated. The models differed depending on whether the 15 family members with a
      diagnosis of schizophrenia spectrum disorders were considered unaffected (a
      "narrow" (N) definition), affected (a "wide" (W) definition), or declared
      "unknown" (U). The entire region between D22S268 and D22S307 is excluded (i.e.,
      lod <-2) for models RN, RW, RU, and IW. Lod scores for the remaining models are
      uniformly negative; albeit, equivocal with respect to the dominant hypothesis
      over a small region between D22S268 and IL2RB. Nonparametric analysis under both
      diagnostic criteria also failed to yield any evidence for a susceptibility locus
      in this region of chromosome 22.

PMID- 9259370
TI  - APOE is linked to Alzheimer's disease in a large pedigree.
AB  - Although previous association studies have demonstrated that the APOE4 allele is
      a risk factor for Alzheimer's disease (AD), its value for the prediction of AD in
      individuals is <100%. The limited predictive value of epsilon4 is also seen in
      multiply affected families where the epsilon4 allele is not tightly linked to AD.
      We analyzed a large pedigree multiply affected with AD by lod score linkage
      analysis at the known loci associated with AD. In this pedigree, the APOE/APOCI
      gene area was linked to the development of AD, while no linkage was detected to
      any of the other loci known to be associated with the disease. In this family,
      then, the inheritance of an epsilon4 allele is highly associated with the early
      development of the disease (mean age of onset, 62 years), and is a good predictor
      of disease. However, given the wealth of evidence for association, but not
      linkage, of APOE4 to AD, we believe this finding suggests that another factor (or
      factors) interact(s) with APOE to precipitate early disease, and produce positive
      linkage results. The nature of this factor presently remains unknown.

PMID- 9259371
TI  - No association or linkage between the 5-HT2a/T102C polymorphism and schizophrenia
      in Irish families.
AB  - Recent findings of an association between schizophrenia and a T102C polymorphism
      at the 5-HT2a receptor gene (particularly with genotype 1-2 and 2-2 and allele 2)
      prompted us to investigate this marker in familial Irish schizophrenic patients,
      their relatives, and ethnically matched unrelated controls; 247 probands and 249
      controls were included in this study. In contrast to some studies, we found no
      evidence of significant differences either in the frequency of the genotypes 1-2
      and 2-2 or allele 2 between the schizophrenic patients and the controls. A
      transmission disequilibrium test, run on the full set of 265 families yielded no
      evidence to support linkage disequilibrium. Linkage analysis with both parametric
      and non-parametric methods yielded strongly negative results. Our findings are
      consistent with other recent association studies which argue against the
      involvement of the 5-HT2a/T102C polymorphism in predisposition to schizophrenia.
      The positive findings reported to date might have occurred by chance or the
      apparent conflict may be due to genetic heterogeneity between samples.

PMID- 9259372
TI  - Population genetics of a functional variant of the dopamine beta-hydroxylase gene
      (DBH).
AB  - Dopamine beta-hydroxylase (E.C. 1.14.17.1; protein abbreviation: DbetaH)
      catalyzes conversion of dopamine to norepinephrine. Previous work identified two
      expressed alleles of the gene encoding DbetaH (locus symbol DBH), containing
      either G or T at nucleotide position 910, resulting in specification by codon 304
      of alanine (DBH*304A) or serine (DBH*304S), respectively. The current study
      employed denaturing gradient gel electrophoresis to identify these alleles, and
      after developing a PCR RFLP for rapid genotyping, estimated the frequencies of
      the alleles in African-Americans, European-Americans, and in several
      geographically dispersed populations (Mbuti, Danes, Adygei, Chinese, Japanese,
      Surui, Maya, and Nasioi). DBH*304A was the most common allele in all populations
      tested, with allele frequencies greater than 0.80 in each case. There was
      significant heterogeneity in allele frequency across population groups. The
      DBH*304S allele was most common in subjects of African descent, and least common
      in East Asians and individuals from indigenous populations of North and South
      America. The frequency of DBH*304S was significantly higher in African-Americans
      (0.16) than in European-Americans (0.06; P < 0.004). Of the four DBH*304S
      homozygotes observed, all were Europeans and three of the four were Danes. Based
      on empirical P-values generated by computer simulation, the observed proportions
      of DBH*304S homozygotes did not differ significantly from Hardy-Weinberg
      expectations in any of the populations after Bonferroni correction for multiple
      comparisons. The observation of significant heterogeneity in DBH*304S allele
      frequency across different population samples demonstrates the importance of
      controlling for population stratification in future studies testing for
      associations between DBH*304S and clinical phenotypes.

PMID- 9259373
TI  - Mapping of a disease locus for familial rapidly progressive frontotemporal
      dementia to chromosome 17q12-21.
AB  - Familial frontotemporal dementia (FTD) is a complex disorder with lack of
      distinctive histopathological markers found in other types of dementia. Most of
      the linkage reports from FTD families map the disease loci to chromosome 17q21
      22. However, FTD is genetically heterogeneous, as linkage also has been reported
      to chromosome 3. In the present study, we investigated the genetics of a Swedish
      family with an early-onset type of rapidly progressive FTD, associated with
      muscular rigidity and akinetic movements. Neuropathological features such as
      severe frontal lobe degeneration, spongy changes, and gliosis were present in
      affected family members. We here report probable linkage to chromosome 17q12-21
      with a maximum two-point lod score of 2.76 at theta = 0 for marker D17S806, and a
      peak multipoint lod score of 2.86 for the same marker. Linkage to chromosome 3
      was excluded, as two-point lod scores of -2.79, and -2.27 at theta = 0.01 for
      markers D3S1603 and D3S1552, respectively, were obtained. Sequencing of the
      translated exons of a strong candidate gene in the linked region of chromosome
      17, the tau gene, failed to identify any mutations segregating with the disease.

PMID- 9259374
TI  - Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers
      to alcoholism, substance abuse and schizophrenia in Southwestern American
      Indians.
AB  - Alcoholism is one of a group of common psychiatric diseases which are well
      defined clinically and strongly influenced genetically, but which are likely to
      be highly heterogeneous in causation, genetically and otherwise. Dopamine is a
      key neurotransmitter in drug-mediated reinforcement. Based on association studies
      with the Taq1A downstream marker, the D2 dopamine receptor has been proposed to
      be the "Reward Deficiency Syndrome Gene." Ser311Cys, a naturally occurring
      variant which largely inactivates transduction after D2 receptor activation, was
      abundant (0.16) in a Southwestern American Indian population we studied.
      Therefore, we were able to provide a critical test of the D2 hypothesis of
      vulnerability to alcoholism by evaluating Ser311Cys and also the intron-2 STR and
      Taq1A markers at this locus in a total of 459 subjects, including 373 sib pairs,
      from large families. The result is that neither alcoholism, substance use
      disorders nor schizophrenia show a relationship to Ser311Cys genotype, even when
      the 15 Cys311/Cys311 homozygous individuals are compared to others. Furthermore,
      sib pair analysis incorporating information across all three sib pair categories:
      concordant affected, discordant and concordant unaffected revealed no effect of
      DRD2 genotype or haplotype on alcoholism or substance use disorder.

PMID- 9259375
TI  - Analysis of 31 families with an apparently autosomal-dominant transmission of
      migraine with aura in the nuclear family.
AB  - We analyzed 31 families selected for an apparently autosomal-dominant mode of
      inheritance of migraine with aura (MA) in the nuclear family. The nuclear
      families were expanded with first- and second-degree relatives. All interviews
      were made by physicians experienced in headache diagnoses. The criteria of the
      International Headache Society were used. The population relative risk among
      children in nuclear families was similar to the estimated population relative
      risk of MA assuming an autosomal-dominant mode of inheritance. The population
      relative risk tended to decrease among first-degree relatives outside nuclear
      families and further among second-degree relatives. Both first- and second-degree
      relatives outside the nuclear families had a statistically significant lower risk
      of MA than expected. Thus, autosomal-dominant inheritance with or without reduced
      penetrance was unlikely. Autosomal-recessive inheritance was unlikely because of
      the unequal sex distribution. Other modes of inheritance were considered as well.
      Mitochondrial and X-linked inheritance were excluded because of paternal
      transmission. The female preponderance was too low to explain sex-influenced
      inheritance. We conclude that MA most likely has a multifactorial inheritance
      even in high-risk families with MA.

PMID- 9259376
TI  - Personality and language characteristics in parents from multiple-incidence
      autism families.
AB  - Several studies have suggested that the genetic liability for autism may be
      expressed in non-autistic relatives of autistic probands, in behavioral
      characteristics that are milder but qualitatively similar to the defining
      features of autism. We employ a variety of direct assessment approaches to
      examine both personality and language in parents ascertained through having two
      autistic children (multiple-incidence autism parents) and parents of Down
      syndrome probands. Multiple-incidence autism parents had higher rates of
      particular personality characteristics (rigidity, aloofness, hypersensitivity to
      criticism, and anxiousness), speech and pragmatic language deficits, and more
      limited friendships than parents in the comparison group. The implications of
      these findings for future genetic studies of autism are discussed.

PMID- 9259377
TI  - Dopamine D4 receptor variants in Chinese sporadic and familial schizophrenics.
AB  - Variation in the number of tandem repeats of a 48 base pair (bp) unit was found
      in the gene of the dopamine D4 receptor (DRD4). The number of repetitions of the
      48bp unit was shown to influence the binding of clozapine, which suggests that
      different alleles may function differently in vivo and affect the pathogenesis of
      schizophrenia. Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic
      probands who had at least one living sibling with a diagnosis of schizophrenia,
      35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic
      patients, and 43 healthy controls without a family history of psychosis. There
      was no significant difference in genotypic or allelic distributions among the
      four groups. Significant differences in the frequencies of two- and seven-repeats
      alleles between the Chinese and Caucasians controls were noted. The present study
      did not support that a particular allele or genotype of the 48bp-repeat of DRD4
      was associated with schizophrenia.

PMID- 9259378
TI  - Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor
      gene (GRIK1) polymorphism.
AB  - Juvenile absence epilepsy (JAE) is a common subtype of idiopathic generalized
      epilepsy (IGE). Hereditary factors play a major role in its etiology. The
      important function of glutamate receptors (GluRs) in excitatory
      neurotransmission, synaptic plasticity, and neurodevelopment suggests their
      involvement in epileptogenesis. A tetranucleotide repeat polymorphism in the non
      coding region of the kainate-selective GluR5 receptor gene (GRIK1) on chromosome
      21q22.1 provides the tool to investigate this candidate gene. The present
      association and linkage study tested the hypothesis that allelic variants of
      GRIK1 confer genetic susceptibility to the pathogenesis of JAE. Our family-based
      association analysis using the haplotype-based haplotype relative risk statistic
      revealed an association of JAE with the nine-repeat containing allele of the
      GRIK1 tetranucleotide polymorphism (chi2 = 8.31, df = 1, P = 0.004). Supportive
      evidence for linkage to a JAE related IGE spectrum (Zmax = 1.67 at GRIK1) under
      an autosomal dominant mode of inheritance and significant allele sharing (P <
      0.05) among the affected family members suggest that allelic variants of GRIK1
      contribute a major genetic determinant to the pathogenesis of JAE-related
      phenotypes.

PMID- 9259379
TI  - Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome:
      evidence for myelin basic protein haploinsufficiency.
AB  - Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate
      disturbed brain myelination in 18q- syndrome, a disorder characterized by mental
      retardation, dysmorphic features, and growth failure. T1-weighted and dual spin
      echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps
      were created for 20 patients and 12 controls. MRI demonstrated abnormal brain
      white matter in all patients. White matter T1 and T2 relaxation times were
      significantly prolonged in patients compared to controls at all ages studied,
      suggesting incomplete myelination. Chromosome analysis using fluorescence in situ
      hybridization techniques showed that all patients with abnormal MRI scans and
      prolonged white matter T1 and T2 relaxation times were missing one copy of the
      myelin basic protein (MBP) gene. The one patient with normal-appearing white
      matter and normal white matter T1 and T2 relaxation times possessed two copies of
      the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral
      myelination in 18q- is associated with haploinsufficiency of the gene for MBP.

PMID- 9259380
TI  - Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive
      compulsive disorder: differences by diagnosis and family history.
AB  - The distribution of obsessive compulsive symptoms was compared in 16 individuals
      with primary obsessive compulsive disorder (OCD) and 16 individuals with Gilles
      de la Tourette syndrome (GTS) and associated obsessive compulsive behaviors
      (OCB). The two groups showed significant differences in the distribution of OC
      symptomatology. Furthermore, those OCD probands who shared a similar symptom
      profile with GTS individuals all had a positive family history of OCD. All of the
      other OCD probands were isolated cases. Implications of this finding on the
      etiology and pathogenesis of the two disorders are discussed.

PMID- 9259381
TI  - High-activity catechol-O-methyltransferase allele is more prevalent in
      polysubstance abusers.
AB  - Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates
      to contribute to genetic components of interindividual differences in
      vulnerability to substance abuse. COMT plays a prominent role in dopaminergic
      circuits important for drug reward, and COMT alleles encode enzymes whose
      activities vary from three- to four-fold. We compared COMT allele frequencies in
      control research volunteers reporting insignificant lifetime use of addictive
      substances with those in volunteers reporting substantial polysubstance use.
      Homozygosity for the high-activity COMT allele was found in 18% of controls, 31%
      of volunteers with high lifetime substance use, and 39% meeting DSMIII-R
      substance abuse criteria [odds ratio (relative risks) 2.0 (control vs. use; 95%
      confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P <
      0.008)]. Individuals with the high-activity COMT variant may have greater genetic
      vulnerability to drug abuse.

PMID- 9259382
TI  - Brain-derived neurotrophic factor gene and schizophrenia in Japanese subjects.

PMID- 9259384
TI  - No evidence of partial trisomy 16p in an autistic calendar savant with Tourette
      syndrome.

PMID- 9259383
TI  - Possible association of a silent polymorphism in the neuronal nicotinic
      acetylcholine receptor subunit alpha4 with common idiopathic generalized
      epilepsies.
AB  - The alpha4 subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA4)
      has recently been identified as the first gene underlying an idiopathic partial
      epilepsy syndrome in human, autosomal-dominant nocturnal frontal lobe epilepsy
      (ADNFLE). CHRNA4 is located in the candidate region for benign familial neonatal
      convulsions and low-voltage EEG on chromosome 20q. In the present study, we
      examined the possible role of CHRNA4 in common subtypes of idiopathic generalized
      epilepsy (IGE), comprising childhood and juvenile absence epilepsy and juvenile
      myoclonic epilepsy (JME), by systematically screening the coding region of the
      gene for sequence variants. We present here a population-based association study
      testing the hypothesis that variants of the CHRNA4 gene confer genetic
      susceptibility to common subtypes of IGE. The missense mutation (Ser248Phe),
      associated with ADNFLE, and four silent polymorphisms in the CHRNA4 gene were
      genotyped in 103 IGE patients and 92 controls by polymerase chain reaction and
      subsequent restriction analysis. Without correction for multiple testing, the
      frequency of the T-allele of the silent CfoI bp595 polymorphism was increased in
      the entire group of IGE patients (f(T) = 0.085) compared to that in the controls
      (f(T) = 0.027). The allelic association was not restricted to any subgroup of IGE
      with either JME or idiopathic absence epilepsies. This result suggests that
      variation of the CHRNA4 gene, or so-far-undetected sequence variants near the
      CHRNA4 locus, confer susceptibility to the common IGE syndromes.

PMID- 9259385
TI  - Lack of association between the apolipoprotein E epsilon4 allele (APOE epsilon4)
      and chronic schizophrenia.

PMID- 9259386
TI  - Polymorphism of FXR1 showing lack of association with autism.

PMID- 9259387
TI  - Ernst Rudin and Nazi euthanasia: another stain on his career.

PMID- 9259389
TI  - Correspondence regarding German psychiatric genetics and Ernst Rudin.

PMID- 9259388
TI  - Ernst Rudin, a Nazi psychiatrist and geneticist.

PMID- 9259390
TI  - Incidence of childhood cancer in Cuba (1986-1990).
AB  - Cancer is an infrequent disease in childhood. However, it is responsible for
      13.06% of child deaths between 1 and 14 years in Cuba. The aim of our work was to
      describe the incidence of childhood cancer in the period 1986 to 1990 using data
      reported to the National Cancer Registry (NCR) of Cuba. All cancer cases between
      0 and 14 years of age reported to the NCR in the period 1986 to 1990, were
      included. The cases were classified histologically, by age and gender. Average
      age-specific and age-standardized rates were calculated; 1428 children were
      registered, an average of 286 each year, with a mean annual rate of 117.8 per
      million. The world-population standardized rate was 120.7 and the male-to-female
      ratio was 0.98. Leukaemias, lymphomas and malignant tumours of the central
      nervous system were the most common childhood neoplasm groups. The majority of
      leukaemias were acute lymphoblastic leukaemias (ALL), and the incidence peak
      extended until 6 years of age. The first peak of incidence of Hodgkin's disease
      is found in older age-groups. Burkitt's lymphoma showed a male-to-female ratio of
      0.44. Most of the hepatic tumours were carcinomas, and only one fourth were
      hepatoblastomas. In bone tumours, similar rates were observed for osteosarcomas
      and Ewing's sarcoma.

PMID- 9259391
TI  - Expression of matrix metalloproteinases and their inhibitors in human
      bronchopulmonary carcinomas: quantificative and morphological analyses.
AB  - The expression of various matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs) in 88 primary bronchopulmonary cancers and in 13 neighbouring
      pulmonary parenchyma samples was quantified by Northern-blot analysis, and
      morphologically examined by in situ hybridization and immunohistochemistry in
      order to evaluate the involvement of MMPs in the pathophysiology of these
      carcinomas and to look for potential markers of aggressivity of lung tumours.
      Northern-blot analysis showed that the predominantly expressed MMPs in
      bronchopulmonary cancers were gelatinase A (66%), its activator MT1-MMP (membrane
      type-1 matrix metalloproteinase) (56%) and stromelysin-3 (61%). MMP expression
      frequencies and mRNA levels increased progressively with malignant phenotype,
      lack of differentiation and TNM stage of the tumours, whereas TIMP expression
      decreased very early during tumour progression. Moreover, the principal MMPs were
      significantly co-expressed in primary tumours, suggesting their co-regulation.
      Morphological studies revealed the expression of MMPs and TIMPs essentially in
      stromal cells in close contact with tumour clusters. These results indicate that
      tumour progression in bronchopulmonary carcinomas implies a progressive
      disruption of the MMP/TIMP balance leading to an excess of several MMPs that act
      in concert in vivo. Furthermore, the fact that stromal cells are the principal
      source of MMPs emphasizes the close cooperation between host cells and cancer
      cells in tumour invasion.

PMID- 9259392
TI  - Tobacco smoking and gastric cancer: review and meta-analysis.
AB  - Although declining, gastric cancer (GC) is estimated to be second in frequency
      worldwide. Major causes appear to be environmental rather than genetic. A
      relationship has been suggested between tobacco smoking and GC. A number of
      epidemiological studies have been performed dealing with this question. All the
      cohort studies showed a significantly increased risk of GC of the order of 1.5
      2.5 for cigarette smokers. Evidence from case-control studies is less consistent.
      We have carried out a meta-analysis on the 40 studies providing a quantitative
      estimate of the association between GC risk and tobacco smoking. Results suggest
      a risk of stomach cancer among smokers of the order of 1.5-1.6 as compared to non
      smokers. The summary relative risk was higher in men (1.59) than in women (1.11).
      Several studies examined the dose-response relationship which existed in 4 cohort
      studies and 6 case-control studies. We estimated the number of GC cases
      attributable to tobacco smoking occurring worldwide: in total, over 80,000 cases
      of GC (11% of all estimated cases) may be attributed to tobacco smoking each
      year. This figure is larger than that estimated for other cancers for which
      association with tobacco smoking is clearly established, such as pancreatic and
      renal cancers.

PMID- 9259393
TI  - Identification of an exon 3 deletion splice variant androgen receptor mRNA in
      human breast cancer.
AB  - Androgens and androgen receptor (AR) are involved in many regulatory processes in
      the growth of female breast cells. Mutations in the AR gene and/or alterations of
      the AR protein sequence may be related to the development and progression of
      breast cancer. Using reverse transcription-polymerase chain reaction we have
      examined 31 female breast-cancer samples, 5 normal female breast tissues and 6
      breast-cancer cell lines for the presence of splice variants of AR mRNA and have
      identified an exon 3 deletion splice variant (delta3AR). The higher expression of
      the variant relative to the wild-type AR (WT AR) was found in 7 breast-cancer
      samples (delta3/WT > 15%) and relatively lower levels of the variant were
      observed in 3 breast-cancer cell lines (delta3/WT < 5%). However, in normal
      breast tissues, expression of the variant was undetectable by Southern blot
      analysis. In vitro translation of the delta3AR mRNA resulted in a variant AR
      protein of about 105 kDa, smaller than the WT AR by about 5 kDa. We thus report
      an exon deletion splice variant of AR mRNA in breast cancer. The variant protein
      is predicted to lack the second zinc finger within the DNA-binding domain and is
      expected to be unable or to have reduced ability to bind to androgen-response
      elements and to activate transcription. The relatively high expression of this AR
      variant in some breast-cancer tissues may indicate its role in regulating the
      growth of these cancers.

PMID- 9259395
TI  - Adipose fatty acids and cancers of the breast, prostate and colon: an ecological
      study. EURAMIC Study Group.
AB  - Animal and ecological studies suggest that linoleic acid intake is related to
      breast-cancer incidence. Analytical epidemiologic studies, however, do not
      support such findings. The primary objective of our ecological study was to
      investigate the association between breast-cancer incidence and linoleic acid
      status across European countries. In addition, other fatty acids and cancer sites
      were studied. Mean fatty acid composition of adipose tissue samples in 11 centres
      from 8 European countries and Israel served as indicators of exposure of the
      population. Figures on cancer incidence for the respective or comparable regions
      were obtained from published data. N-6 fatty acids in adipose tissue ranged from
      10.4 in Helsinki to 24.6 g/100 g fatty acids in Jerusalem. N-6 fatty acids were
      not associated significantly with breast, colon or prostate cancer. Cancers of
      the breast and colon were associated negatively with cis-mono-unsaturated fatty
      acids and positively with trans fatty acids. Despite a large range in intake, we
      found no evidence of a positive association between n-6 fatty acid status and
      breast cancer, but associations were observed between other fatty acids and
      cancer. Differences in linoleic acid intake cannot explain risk differences in
      breast-cancer incidence between affluent countries, while associations of other
      fatty acids with cancer rates may reflect cultural differences.

PMID- 9259394
TI  - mRNA expression of ligands of the epidermal-growth-factor-receptor in the uterus.
AB  - Six different ligands of the epidermal-growth-factor receptor (EGFR) have been
      identified in the past. In some cervical squamous-cell carcinomas, an increased
      amount of proteins binding to the EGFR has been reported. In order to identify
      the mRNA of EGFR ligands (EGFRL), which might be overexpressed in cervical and
      endometrial cancers, we performed semi-quantitative reverse
      transcription/polymerase chain reactions (RT-PCR) for all 6 EGFRL in RNA extracts
      of normal and malignant tissue samples of the human uterus. PCR products from RNA
      extracts of 83 patients were quantitated relative to the housekeeping gene and
      internal standard pyruvate dehydrogenase by analyzing the PCR kinetics of product
      synthesis. In extracts of normal cervix, the level of mRNA expression of the
      EGFRL was significantly higher than in endometrium. No significant difference was
      detected between normal cervix and cervical carcinomas. However, both in cervical
      and in endometrial cancers, mRNA expression was non-parametrically distributed
      and in some cervical cancers overexpression of transforming growth factor alpha
      (TGF-alpha), amphiregulin or EGF was observed. In endometrial cancers, mRNA
      levels of all EGFRL were higher than in normal endometrium. This increase was
      significant (p < 0.005) for TGF-alpha and amphiregulin. Thus, TGF-alpha mRNA is
      overexpressed in approximately 10% of cervical cancers and in the majority of
      endometrial cancers. Since TGF-alpha anti-sense therapy might represent a future
      strategy in such cancers, we also determined the absolute level of TGF-alpha mRNA
      expression by quantitative PCR using a cloned standard.

PMID- 9259396
TI  - Clonal HTLV-I-infected CD4+ T-lymphocytes and non-clonal non-HTLV-I-infected
      giant cells in incipient ATLL with Hodgkin-like histologic features.
AB  - Lymph nodes from the incipient or early neoplastic phase of adult T-cell
      leukemia/lymphoma (ATLL) histologically resemble Hodgkin's disease. Integrated
      proviral human T-lymphotrophic virus type I (HTLV-I) has been demonstrated in
      such lesions. We studied 18 patients with this disease, and about half of the
      cases developed typical ATLL within 2 or 3 years. In all cases, either mono- or
      oligoclonal cell populations with proviral HTLV-I DNA were detected by Southern
      blot analysis and/or inverse polymerase chain reaction (IPCR). In addition,
      either a mono- or oligoclonal rearrangement of T-cell receptor genes was
      demonstrated. Giant cells with Reed-Sternberg-like histological features revealed
      CD15 and CD30 positivity. The background infiltrating lymphocytes represented
      either no or only minimal nuclear abnormalities with a CD4+ T-cell phenotype. In
      less than half of all cases, Epstein-Barr virus (EBV) infected the giant cells. A
      mixed EBV-A and -B type was found in 3, and a multiple genotype of EBV lymphocyte
      determined membrane antigen (LYDMA) was found in 6 cases. These results could
      have been due to the immunodeficient status of the patients. A single-cell PCR of
      the giant cell, B cell, CD4+ or CD8+ T cells could be performed after cell
      sorting in 4 cases. HTLV-I infection was frequently found in the CD4+ T cells,
      but in neither the giant cells nor the B cells. The CD4+ T cells exhibited
      clonality. The giant cells showed various PCR products of IgH, and also expressed
      recombination activating genes (RAG). In summary, the giant cells were reactive
      cells, which resembled the immature B-lineage cells, while HTLV-I infected the
      CD4+ T cells, which demonstrated clonality. Based on these above findings, we
      consider CD4+ cells to play an important role in ATLL tumorigenesis.

PMID- 9259397
TI  - Loss of heterozygosity at the TP53 gene: independent occurrence from genetic
      instability events in node-negative breast cancer.
AB  - TP53 abnormalities have been reported as an early event in the process of
      cellular transformation of human breast cancers, and involved in mammary-tumor
      evolution, from in situ to invasive disease. In this study, node-negative (N-)
      tumors were examined for TP53 allelic loss in relation to different genetic
      instability events, including allelic loss at chromosome 17p13.3 and c-H-ras-1
      loci, as well as alteration of the c-myc and c-erbB-2/neu oncogenes. TP53 allelic
      loss was analyzed to determine whether such an abnormality was the more
      important, among other genetic events, in the N- tumors, whether it appeared
      independently of these genetic events, and whether accumulation of genetic events
      arises in this group of breast tumors. Clinicopathological parameters were also
      examined. Loss of heterozygosity (LOH) at the TP53 gene appears the most frequent
      alteration detected (26% vs. 13%, 8%, 9% and 3% for LOH at D17S30 and c-H-ras-1
      loci, and amplification of c-myc and c-erbB-2/neu respectively). There was no
      association between LOH at the TP53 locus and other genetic events. Among
      clinicopathological parameters, significant associations were observed only with
      estrogen-receptor-negative tumors (p = 0.05). Our results demonstrate that LOH at
      TP53 arises more frequently in the N- breast cancer, thus supporting earlier
      findings suggesting that TP53 abnormality has a role early in the pathogenesis of
      breast lesions. Moreover, the data indicate that accumulation of many genetic
      events occurs at a low level in N- breast tumors, and that TP53 abnormality
      occurs independently of these genetic events.

PMID- 9259398
TI  - Cytogenetic findings in metastases from colorectal cancer.
AB  - Eighteen tumor samples from 11 patients with metastatic colorectal cancer were
      cytogenetically analyzed after short-term culturing. Of the 13 metastases
      examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In
      5 of the 11 patients, matched samples from the primary tumor and lymph node
      metastases were analyzed. Cytogenetic similarities between the primary and
      secondary lesions were found in all 5 cases, indicating that many of the
      chromosomal aberrations presumably occurred before disease spreading took place.
      Compared with the primaries, the metastases appeared to exhibit decreased clonal
      heterogeneity but, concurrently, an increase in the karyotypic complexity of
      individual clones. Among the aberrations recurrently found in metastatic lesions
      were del(1)(p34), i(17)(q10), -18, -Y, -21, +7 and +20, all of which have been
      seen repeatedly in previous series of primary colorectal carcinomas, and
      del(10)(q22) and add(16)(p13), which so far have not been associated with primary
      tumors and which may play a particular pathogenetic role in the metastatic
      process.

PMID- 9259399
TI  - Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer.
AB  - Hormonal breast cancer therapies have traditionally been considered cytostatic,
      but recent pre-clinical data suggest that anti-oestrogens can induce apoptosis.
      The aim of this study was to assess whether tamoxifen (TAM) and ICI 182780 (ICI)
      could induce apoptosis in human breast cancer, and whether this was related to
      oestrogen receptor status. We measured apoptosis in primary breast cancer
      patients before and after pre-surgical treatment with 20 mg/day TAM (study 1) or
      6 or 18 mg/day ICI (study 2). In each study there was a randomised non-treatment
      (NT) control group. TAM significantly increased apoptotic index (AI) in ER+ but
      not in ER- tumours. There was a significant increase in AI following treatment
      with ICI. Insufficient pairs of samples were available to determine whether this
      change was confined to ER+ tumours, but in a cross-sectional analysis AI was
      significantly higher in excision biopsies for ICI-treated than NT patients for
      ER+ but not ER- tumours. Our results provide clinical evidence that apoptosis may
      be induced in ER+ primary breast cancer by both non-steroidal and steroidal anti
      oestrogens.

PMID- 9259400
TI  - Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an
      HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein.
AB  - There is good evidence for an association between Epstein-Barr virus (EBV) and
      Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is
      detectable in Reed-Sternberg (RS) cells and there is expression of the viral
      nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2
      has been demonstrated at the mRNA level, and it is presumed that the protein is
      expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope
      presented to cytotoxic T-cells which is restricted through the HLA class I
      antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive
      Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive
      individuals would be under-represented among Caucasians with EBV-associated HD.
      HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain
      reaction, for 276 individuals including 176 cases of HD. There was no significant
      difference between the frequency of HLA-A*02 positivity in HD cases and controls,
      and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14
      cases of EBV-associated HD were further subtyped using nested PCR; all except one
      case were found to be A*0201-positive. We therefore investigated whether there
      was any evidence for mutation of the epitope representing amino acids 426-434 of
      LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide
      sequence encoding this epitope was identical to the published sequence; in the
      remaining case there was a mutation which would not be expected to alter the
      conformation of the epitope. Overall, our data suggest that other mechanisms of
      immune escape must be operative in EBV-associated HD.

PMID- 9259401
TI  - Tumor-infiltrating dendritic cells are defective in their antigen-presenting
      function and inducible B7 expression in rats.
AB  - Tumors are tolerated by the immune system notwithstanding the expression of tumor
      associated antigens. PROb tumor cells, derived from a rat colon carcinoma, are
      rejected by tumor-immune hosts but give rise to progressive tumors in naive
      hosts. Paradoxically, these tumors are heavily infiltrated by dendritic cells
      that express MHC class II and ICAM-1. These tumor-infiltrating dendritic cells
      (TiDCs) could be expected to process and present to T cells the antigens released
      by the adjacent tumor cells. Indeed, we report here that TiDCs, compared with
      splenic dendritic cells, are poor stimulators of primary allogeneic T-cell
      proliferation and cytokine [interleukin-2 (IL-2) and interferon-gamma]
      production. Most of them (89-97%) do not express B7, an essential co-stimulatory
      signal for T cells, even after a culture period allowing B7 up-regulation on
      epidermal Langerhans cells. GM-CSF in association with tumor necrosis factor
      alpha or IL-4, or cell-associated CD40-ligand, all known to be potent stimulators
      of B7 expression on other dendritic cells, did not restore B7 expression by
      TiDCs. After a first exposure to TiDCs, allogeneic T-cell response to a second
      challenge to splenic dendritic cells was decreased. The failure of most dendritic
      cells infiltrating PROb tumors to express B7, even after stimulation, may
      contribute to their poor capacity to stimulate T cells and could play a role in
      the immune tolerance allowing tumor growth.

PMID- 9259402
TI  - Ectopic activation of lymphoid high mobility group-box transcription factor TCF-1
      and overexpression in colorectal cancer cells.
AB  - Physical interaction between the lymphoid high mobility group (HMG)-box
      architectural transcription factors TCF/LEF and beta-catenin is associated with
      translocation of the heteromeric complex to the nucleus and regulation of target
      gene expression. Since formation of molecular complexes among beta-catenin, E
      cadherin, p300apc and TCF/LEF depends on balanced expression of these
      constituents, we investigated the biosynthesis of TCF-1 in colorectal cancer.
      Here we report detailed analyses of activation and overexpression of lymphoid
      transcription factor TCF-1 in human colorectal cancer-derived cell lines.
      Northern blot analyses revealed considerable steady-state expression levels of
      TCF-1 mRNA of normal size. Genomic rearrangement of the 5' flanking region of the
      TCF-1 gene was excluded as a cause of ectopic expression. By contrast, CAT
      reporter constructs depending on a 515-bp T-cell-regulated TCF-1 genomic upstream
      region were significantly activated in epithelial tumor cells. RT-PCR analyses
      revealed a heterogeneic population of mRNA isoforms due to alternative splicing
      in the TCF-1 gene. On Western blots of colorectal cancer cells, the TCF-1
      specific monoclonal antibody 7H3 detected a similar heterogeneous spectrum of TCF
      1 specific polypeptide chains. Interestingly, overexpression of TCF-1-specific
      splice forms correlated with the metastatic behavior of the analyzed cells and
      with overproduction of lymphoid tyrosine protein kinase p56(lck). We conclude
      that ectopic expression of the HMG-box factor TCF-1 is associated with late
      events in tumor progression.

PMID- 9259403
TI  - Inhibition of tumorigenicity in lung adenocarcinoma cells by c-erbB-2 antisense
      expression.
AB  - The lung carcinoma cell line Calu3, which overexpresses the c-erbB-2 oncogene,
      was stably transfected with antisense (AS) cDNA constructs encompassing different
      regions of the c-erbB-2 gene. Transfected cells were analyzed for their
      tumorigenic properties in vitro and in nude mice. Two independent clones, AS F1
      (low erbB-2 expressor) and AS B12 (high erbB-2 expressor), as well as the
      polyclonal Calu3/AS 5', were selected for these analyses. In Calu3/AS 5'
      transfected cells and in the AS F1 clone, c-erbB-2 RNA and protein levels were
      lower than those detected in the parental cell line and the AS B12 clone.
      Anchorage-independent growth and tumor take were also significantly reduced.
      Furthermore, cells derived from primary tumors of Calu3/AS 5', AS F1 and AS B12
      lost the AS c-erbB-2 DNA insert but retained the gene for G418 resistance. Our
      results suggest that a correlation between c-erbB-2 overexpression and
      tumorigenicity may exist in the Calu3 lung carcinoma cell line.

PMID- 9259404
TI  - Pancreatic cancer in rats and hamsters does not induce IAPP-related
      hyperglycaemia.
AB  - Many patients with exocrine pancreatic cancer develop diabetes mellitus due to
      insulin resistance. This may relate to concurrent over-production of islet
      amyloid polypeptide (IAPP) by the pancreatic beta cells. We investigated the
      effects of pancreatic cancer on circulating IAPP and glucose homeostasis in
      azaserine-treated rats (developing acinar pancreatic tumours) and BOP-treated
      hamsters (developing ductular pancreatic tumours). Glucose, insulin and IAPP
      levels in plasma were neither affected in azaserine-only treated rats nor in
      animals with enhanced carcinogenesis after chronic caerulein treatment. Azaserine
      treated rats on a high-fat diet had decreased insulin levels and enhanced
      IAPP/insulin ratios in plasma, without hyperglycaemia. All BOP-treated hamsters
      showed pancreatic carcinogenesis at 6 months post-treatment. Supranormal plasma
      glucose levels in animals on a low-fat diet were the only change observed. After
      a second 6-month period, subnormal plasma glucose levels, at least 4-fold
      decreased plasma insulin and up to 2-fold decreased plasma IAPP levels were
      present in all hamsters. Remarkably, both in azaserine-treated rats on high-fat
      and in BOP-treated hamsters, decreased insulin levels and elevated IAPP/insulin
      ratios are not associated with hyperglycaemia. In contrast to humans with
      pancreatic cancer, IAPP over-production and hyperglycaemia do not develop in rats
      and hamsters with (pre-)neoplastic pancreatic lesions.

PMID- 9259405
TI  - Ectopic expression of platelet integrin alphaIIb beta3 in tumor cells from
      various species and histological origin.
AB  - The integrin alphaIIb beta3 is a membrane receptor which was considered to be
      expressed only in cells of megakaryocytic lineage. We have shown that alphaIIb
      beta3 is expressed in mouse melanoma B16a cells, and in human prostate
      adenocarcinoma cells. The purpose of this study was to determine whether the
      megakaryocytic product alphaIIb beta3 was functionally expressed in other non
      megakaryocyte lineage tumor cells. By using the reverse transcription polymerase
      chain reaction (RT-PCR), we have obtained data demonstrating that alphaIIb beta3
      is expressed in a variety of tumor cell lines (17) derived from different species
      (human, rat and mouse) and of different histological origins (skin, blood, lung,
      liver, kidney, cervix, colon, bladder, breast and prostate). Immunostaining of
      tumor cells with a monoclonal antibody (MAb) to alphaIIb beta3 demonstrates that
      alphaIIb beta3 protein is also expressed in tumor cells. A protein kinase C
      activator PMA stimulates adhesion of tumor cells to fibronectin and fibrinogen,
      and this stimulated adhesion is blocked by a function-blocking MAb directed to
      alphaIIb beta3. Our results indicate that the megakaryocytic gene product
      alphaIIb beta3 integrin is widely expressed among tumor cells of non
      megakaryocytic lineage, suggesting that ectopic expression of this integrin may
      play an important role in tumor progression.

PMID- 9259406
TI  - Molecular targeting of mitomycin C chemotherapy.
AB  - In 10 human cancer cell lines, the activity of mitomycin C (MMC) was found to be
      determined by an interplay between activation by DT-diaphorase (DTD) and
      inactivation by glutathione S-transferase (GST). NADPH/cytochrome P-450 reductase
      was not responsible for MMC activation and expression of MDRI (Mr 170,000 P
      glycoprotein), and MRP (multidrug resistance-associated protein) genes did not
      relate to MMC resistance. Gene expression analysis for NQO1 (DTD gene) and GSTpi
      predicted which enzyme activity predominated in a cell line, except K562 and
      K562/DOX. For tumors with DTD activity only, MMC given by itself was most active.
      In cell lines in which DTD action was predominant, tumor selectivity was achieved
      by enhancing DTD-mediated activation with m-iodobenzylguanidine and
      hyperglycemia, which reduced the intra-tumoral pH. KW2149, a novel MMC analogue
      activated by glutathione, was most active against tumors in which GSTpi
      predominated. These various enzyme-specific effects could be observed even in
      cell lines derived from tumors with multidrug resistance. Such MMC treatment
      based on cell enzymology may enhance significantly MMC efficacy, helping to
      overcome multidrug resistance.

PMID- 9259407
TI  - New nortriterpenoid isolated from anti-rheumatoid arthritic plant, Tripterygium
      wilfordii, modulates tumor growth and neovascularization.
AB  - Preparations of Tripterygium wilfordii, "Thunder God vine", have been used in
      China to treat rheumatoid arthritis. Rheumatoid arthritis, as well as solid
      tumors, is closely associated with neovascularization. Antiarthritic drugs
      therefore may modulate tumor growth as well as neovascularization. We found that
      a compound purified from T. wilfordii, the nortriterpenoid, demethylzeylasteral
      (TZ-93), inhibited the proliferation of vascular endothelial cells approximately
      30 times more effectively than it did for the proliferation of human tumor cells.
      In in vitro assays using bovine aortic endothelial cells, TZ-93 at non-toxic
      doses inhibited cell migration, expression of urokinase-type plasminogen
      activator (uPA) mRNA and uPA activity. Exogenous addition of uPA restored the
      inhibitory effect of TZ-93 on cell migration. In dorsal air-sac assays in BALB/c
      mice, the oral administration of 3 mg/kg/day TZ-93 for 5 days partially
      inhibited, and 30 mg/kg/day almost completely abrogated, the development of
      capillary networks induced by human hepatoblastoma cells. Similarly, 0.3
      mg/kg/day TZ-93 partially inhibited, and 3 or 30 mg/kg/day almost completely
      blocked, the growth of mouse B16-F10 melanoma cells in a tumor implantation
      assay. The highest dose of TZ-93 significantly reduced the growth of well
      vascularized tumors with volumes of more than 500 mm3. TZ-93 treatment of tumor
      bearing mice significantly decreased the density of microvessels in the tumors.
      We conclude that TZ-93 may be useful in treating highly vascularized and
      metastatic tumors as well as other angiogenic diseases.

PMID- 9259409
TI  - CEP-751 inhibits TRK receptor tyrosine kinase activity in vitro exhibits anti
      tumor activity.
AB  - The present report describes the in vitro and in vivo profile of CEP-751, a novel
      receptor tyrosine kinase inhibitor. CEP-751 at 100 nM inhibits the receptor
      tyrosine kinase activity of the neurotrophin receptors trkA, trkB and trkC. CEP
      751 has no effect on activity of receptors for EGF, IGF-I, insulin or on erbB2;
      inhibition of receptors for PDGF and bFGF was observed but occurred with lesser
      potency than inhibition of trk. CEP-751 exhibited anti-tumor efficacy against
      tumors derived from NIH3T3 cells transfected with trkA. Inhibition of trk
      phosphorylation could also be measured in these tumors, suggesting that anti
      tumor efficacy of CEP-751 is related to inhibition of trk receptor tyrosine
      kinase activity. CEP-751 was found to be without effect when administered to nude
      mice bearing SK-OV-3 tumors, which overexpress erbB2 receptors, providing further
      evidence that inhibition of tumor growth may be related to inhibition of trk
      receptor tyrosine kinase activity. Our data indicate that CEP-751 is a potent trk
      inhibitor which possesses anti-tumor activity.

PMID- 9259408
TI  - The paracrine role of tumour-derived mIL-4 on tumour-associated endothelium.
AB  - Interleukin-4 (IL-4) has been demonstrated to possess anti-tumourigenic
      properties in vivo which is initially attributed to the infiltration of
      eosinophils proposed to occur by IL-4 binding to its receptors on endothelial
      cells, thereby mediating eosinophil adhesion. We have investigated whether the
      binding of IL-4 to receptors on endothelial cells could elicit other biological
      responses which may also play a role in tumour inhibition, such as angiogenesis.
      We have demonstrated that mouse IL-4 (mIL-4) down-regulates the expression of one
      of the receptors for VEGF, VEGF-R2, on endothelial cells in vitro. By generating
      stable transfectants of C6 glioma cells that express mIL-4 under a tetracycline
      responsive promoter system, we were able to apply tight regulatory control of mIL
      4 expression in vivo. Subcutaneous implantation of mIL-4/C6 cell lines in nu/nu
      mice revealed that tumour growth is inhibited by mIL-4 expression. mIL-4
      expressing tumours were demonstrated to have a reduced level of vascularisation
      compared with controls, in addition to a high degree of eosinophil infiltration.
      Our results suggest that mIL-4 has bimodal biological roles in potentiating
      tumour inhibition in athymic mice: the suppression of angiogenesis and the
      augmentation of the host local immune response.

PMID- 9259410
TI  - DX-8951f, a water-soluble camptothecin analog, exhibits potent antitumor activity
      against a human lung cancer cell line and its SN-38-resistant variant.
AB  - We previously reported that DX-8951f, a novel water-soluble camptothecin analog,
      significantly inhibits the growth of various human and murine tumors in vitro and
      in vivo. The antitumor effects and topoisomerase I inhibitory activity of DX
      8951f are stronger than those of other current camptothecin analogs. In this
      study, we established an SN-38-resistant cell line, PC-6/SN2-5, from the human
      oat cell carcinoma PC-6 cell line by a stepwise selection system, investigated
      the mechanism of resistance of this cell line and then compared the antitumor
      activity of camptothecin analogs against the cell line. PC-6/SN2-5 cells were
      resistant to SN-38 (32-fold) and SK&F 104864 (topotecan; 14-fold), but barely
      resistant to CPT-11 (3-fold) and DX-8951f (2-fold). Topoisomerase I protein
      levels and topoisomerase I activities of parental cells were similar to those of
      resistant cells. Determination of the cellular drug concentration by either flow
      cytometric analysis or the high-performance liquid chromatography method
      confirmed that the cellular accumulation of SN-38 and topotecan was significantly
      reduced in PC-6/SN2-5 cells, whereas that of DX-8951f was only slightly reduced.
      Furthermore, DX-8951f stabilized the cleavable complex formations in intact PC
      6/SN2-5 cells as well as in parental cells, but SN-38 and topotecan did not in
      the resistant cells. Our data suggest that PC-6/SN2-5 cells may have acquired
      resistance to camptothecin analogs by a decrease in intracellular drug
      accumulation and that DX-8951f may have the potency to overcome such a type of
      resistance mechanism induced by camptothecin compounds.

PMID- 9259411
TI  - Leukemia inhibitory factor induces apoptosis and proliferation of human carcinoma
      cells through different oncogene pathways.
AB  - Leukemia inhibitory factor (LIF) affects the growth of carcinoma cells, and we
      thus analyzed its underlying mechanisms. Carcinoma cells constitutively express
      LIF mRNA, and 23 lines (92.0%) and all (100%) of 25 lines express LIF receptor
      mRNAs of LIFRbeta and gp130, respectively. Exogenous addition of LIF promoted
      significant cell proliferation in 4 lines (MCF-7, ZR-75-1, Hs-700T and Panc-1)
      and suppressed cell growth in 3 lines (AZ-521, GBK-1 and HT-29). LIF
      significantly induced an immediate early response of genes c-fos and junB 3 hr
      after stimulation, but not of c-jun during the process of proliferation of MCF-7
      and Hs-700T cells, with maximum levels at 30-60 min. The cell-cycle-related gene
      cyclin E was also induced in MCF-7 and Hs-700T cells, whereas cyclinA, cdk2, c
      myc, c-myb and p53 mRNAs were not induced. On the other hand, LIF inhibited
      growth and increased the rate of cell death of AZ-521 and GBK-1 cells. LIF
      increased the number of TUNEL-positive cells in AZ-521 cells and DNA
      fragmentation in AZ-521 and GBK-1 cells. LIF induced apoptosis related genes c
      myc and ICE during suppression of cell growth, but p53, p21, c-fos, cyclin A and
      cyclin E were not induced. Our results suggest that LIF is linked to cell
      proliferation and apoptosis in some human carcinoma cell lines. It is considered
      that this is related to differences in signal transduction and induction of
      oncogenes.

PMID- 9259412
TI  - WT1 contributes to leukemogenesis: expression patterns in 7,12
      dimethylbenz[a]anthracene (DMBA)-induced leukemia.
AB  - The Wilms'-tumor gene WT1 may have a different function from a tumor-suppressor
      gene in some leukemias. Using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      rat leukemia system, we examined whether WT1 expression was involved during
      leukemogenesis, since this model enabled us to analyze cells altered by DMBA at
      various stages of leukemogenesis. By the semi-quantitative reverse-transcriptase
      polymerase chain reaction (RT-PCR) method, WT1 expression was detected in 15
      (71%) of 21 DMBA-induced erythroblastic leukemias. Among 15 WT1-expressing
      leukemias, GATA-1, which is an erythroid-specific transcription factor and might
      regulate WT1 expression, was also expressed in 13 cases (p < 0.05). On the other
      hand, WT1 expression was not detected in any normal or early pre-leukemic rats
      and was detected in 1 of 8 rats in late pre-leukemic stages. These results showed
      that cells with a high expression level of WT1 tended to develop into leukemia
      and that WT1 contributed to leukemogenesis in the late stage, suggesting that the
      expression of WT1 plays an important role in cell proliferation and in
      maintaining the viability of some leukemia cells.

PMID- 9259413
TI  - Identification of a novel breast-cancer-anti-estrogen-resistance (BCAR2) locus by
      cell-fusion-mediated gene transfer in human breast-cancer cells.
AB  - Development of anti-estrogen resistance limits the benefit of endocrine therapy
      of breast cancer. The mechanistic basis for resistance to the anti-estrogen
      tamoxifen may involve (epi)genetic alterations within tumor cells. We have
      initiated a random search for genes allowing estrogen-dependent ZR-75-1 human
      breast-cancer cells to proliferate in the presence of tamoxifen. The strategy was
      based on insertion mutagenesis of ZR-75-1 cells using defective retrovirus and
      subsequent identification of common integration sites. As an alternative approach
      to identify integration loci involved in anti-estrogen resistance, we have
      applied cell fusion. Integration regions from lethally irradiated, tamoxifen
      resistant cells were transferred to hygromycin B-resistant ZR-75-1 cells. Somatic
      cell hybrids were established by selection for resistance to G418 (encoded by the
      integrated virus) and hygromycin B. Individual integration loci were thus
      separated among different cell hybrids and tested for their role in anti-estrogen
      resistance. Analysis of a panel of 29 somatic-cell hybrids revealed that
      tamoxifen resistance co-segregated with only 1 of the 2 integration loci present
      in the tamoxifen-resistant donor cell line. This locus was further identified as
      a common integration site in our panel of tamoxifen-resistant cell clones. Our
      results designate this integration site as the second breast-cancer-anti-estrogen
      resistance locus (BCAR2), which most likely contains a gene responsible for the
      anti-estrogen-resistant phenotype in close proximity to the integrated virus. Our
      data also imply that individual genes can alter the estrogen dependency of human
      breast-cancer cells in a dominant manner in vitro.

PMID- 9259414
TI  - Patient education: essential to good health care for patients with chronic
      arthritis.

PMID- 9259415
TI  - Self antigens and epitope spreading in systemic autoimmunity.

PMID- 9259416
TI  - Allelic markers close to prolactin are associated with HLA-DRB1 susceptibility
      alleles among women with rheumatoid arthritis and systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate linkage disequilibrium between HLA-DRB1 disease
      susceptibility alleles and microsatellite markers close to the prolactin gene,
      among women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)
      and normal controls. METHODS: DNA from 89 women with RA, 76 women with SLE, and
      94 controls was typed for HLA-DRB1 status and D6S422 and D6S285, 2 highly
      polymorphic microsatellite markers close to the prolactin gene. RA patients were
      stratified by DRB1*0401 status, and SLE patients were stratified by *0301 status.
      RESULTS: There was an excess frequency of D6S422*1 among SLE patients with
      DRB1*0301 (odds ratio [OR] 3.1). The frequency of this allele was also slightly
      in excess among RA patients with DRB1*0401 (OR 1.9). D6S285*5 was also in excess
      among female RA patients with DRB1*0401 (OR 3.5), and was slightly increased
      among female SLE patients with DRB1*0301. None of these alleles were found to be
      increased among *0401-positive or *0301-positive controls. CONCLUSION: These data
      indicate that there may be linkage disequilibrium between HLA-DRB1 alleles and
      microsatellite marker alleles close to the prolactin gene among women with RA and
      SLE. This suggests the possibility of extended haplotypes encoding for HLA-DRB1
      susceptibility and high prolactin production, which contribute to susceptibility
      to both RA and SLE.

PMID- 9259417
TI  - Association of rheumatoid arthritis with an amino acid allelic variation of the T
      cell receptor.
AB  - OBJECTIVE: To investigate allelic variations of T cell receptor residues for a
      contribution to rheumatoid arthritis (RA) susceptibility. METHODS: We conducted
      an RA case-control study involving 1,579 northwest Europeans: 766 patients with
      erosive and rheumatoid factor-positive disease and 813 control subjects.
      Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and
      TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms.
      The TCRAV8S1 association was confirmed by restriction fragment length
      polymorphism. RESULTS: In the systematic study (77 patients and 119 controls), an
      increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This
      finding was replicated in 2 further populations, one from France (212 patients
      and 254 controls) and the other from Britain (477 patients and 440 controls),
      with a similar odds ratio (OR), which allowed pooling of the data and
      confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P =
      0.008). CONCLUSION: These findings show evidence that TCRA is an RA
      susceptibility locus.

PMID- 9259418
TI  - Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium.
AB  - OBJECTIVE: To show the eventual presence and extent of production of matrix
      metalloproteinase 13 (MMP-13, or collagenase 3) in rheumatoid synovial tissue
      samples and extracts, and to assess the inhibition characteristics of recombinant
      MMP-13. METHODS: Immunohistochemical avidin-biotin-peroxidase complex
      staining/morphometry was used to analyze MMP-13-positive cells in situ. Neutral
      salt extraction of synovial tissue, electrophoresis of the extract in different
      buffer systems, and Western blotting were also used. The inhibitory properties of
      doxycycline, clodronate, pamidronate, and D-penicillamine for recombinant enzyme
      were determined with a soluble type II collagen assay. RESULTS: MMP-13 was
      detected in fibroblast- and macrophage-like mononuclear cells in the synovial
      lining and stroma and in vascular endothelial cells. The overall expression of
      MMP-13 in these cells in the synovial stroma was high in rheumatoid arthritis (86
      +/- 12%) compared with osteoarthritis (17 +/- 5%) patient samples (P = 0.0027).
      In a high-pH native electrophoresis gel, immunoreactivity to anti-MMP-1 and anti
      MMP-13 were clearly separated, with anti-MMP-13-immunoreactive material migrating
      faster than anti-MMP-1-immunoreactive material. Finally, in contrast to MMP-1 and
      MMP-8, MMP-13 was found to be relatively resistant to the inhibitory effects of
      doxycycline and clodronate in vitro. CONCLUSION: Due to its localization in
      synovial tissue, its substrate profile, increased expression, and relative
      resistance to known MMP inhibitors, MMP-13 is suggested to play a major role in
      the pathogenesis of tissue destruction in rheumatoid arthritis.

PMID- 9259419
TI  - Effects of pulse methylprednisolone on inflammatory mediators in peripheral
      blood, synovial fluid, and synovial membrane in rheumatoid arthritis.
AB  - OBJECTIVE: To establish whether the clinical efficacy of pulse methylprednisolone
      (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory
      cytokines within the peripheral blood, synovial membrane, or synovial fluid
      compartments. METHODS: Eighteen patients with active rheumatoid arthritis (RA)
      were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients,
      10 knees) were obtained before and at 4 and 24 hours after MP therapy.
      Interleukin-1beta (IL-1beta), IL-8, and tumor necrosis factor alpha (TNFalpha)
      were measured by enzyme-linked immunosorbent assay and biologic assays;
      prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10
      patients, arthroscopically directed synovial biopsies were obtained before and at
      24 hours after treatment, at disease relapse (4 patients), and after retreatment
      (1 patient). Membranes were stained by immunohistochemical techniques with
      monoclonal antibodies against TNFalpha, IL-8, IL-1beta, and the IL-1 receptor
      antagonist protein (IL-1Ra). RESULTS: MP therapy was associated with a rapid
      (within 24 hours) and substantial decrease in the expression of TNFalpha in the
      lining and sublining regions of the synovial membrane, as well as substantial
      decreases in the levels of TNFalpha in serum and synovial fluid. There was also
      reduced IL-8 expression in the synovial lining, as well as reduced synovial fluid
      IL-8 levels. No effect on synovial membrane IL-1beta and IL-1Ra or synovial fluid
      IL-1beta and PGE2 was found. CONCLUSION: MP therapy rapidly reduces IL-8 and
      TNFalpha levels in the synovial compartment, with cytokine changes in the serum
      and synovial fluid reflecting the changes in the synovial membrane. Alterations
      in TNFalpha expression in the synovial membrane correlated with clinical response
      to, and subsequent relapse after, MP therapy.

PMID- 9259420
TI  - The B cell repertoire of patients with rheumatoid arthritis. II. Increased
      frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat-shock
      protein 60 or human type II collagen in synovial fluid and tissue.
AB  - OBJECTIVE: A qualitative and quantitative analysis of the functional, antigen
      specific B cell receptor repertoire of patients with rheumatoid arthritis (RA) in
      synovial and peripheral compartments. METHODS: B cells were activated to grow and
      differentiate at high efficiency in vitro under limiting-dilution conditions.
      Isotype and specificity of the secreted Ig were tested by enzyme-linked
      immunosorbent assay. RESULTS: In contrast to peripheral B cells, most synovial B
      cells had already switched to IgG/IgA in vivo. The frequencies of B cells
      specifically recognizing foreign antigens were decreased within the synovial
      population, whereas the frequencies of B cells specific for type II collagen,
      mycobacterial heat-shock protein 60 (hsp60), or IgG Fc fragments were
      significantly increased, revealing a negative correlation in terms of
      frequencies. CONCLUSION: B cells specific for human type II collagen, hsp60, and
      IgG Fc fragments are produced and/or expanded locally within the affected joints
      of RA patients. Thus, the specific immune system is definitely involved in the
      local inflammatory and destructive processes.

PMID- 9259421
TI  - Development of in vitro model systems for destructive joint diseases: novel
      strategies for establishing inflammatory pannus.
AB  - OBJECTIVE: To establish a novel 3-dimensional (3-D) in vitro model for the
      investigation of destructive processes in rheumatoid arthritis (RA). METHODS: Two
      distinct culture systems were developed, consisting of RA synovial membrane and
      articular cartilage explants or interactive RA synovial cell/chondrocyte cultures
      embedded in 3-D fibrin matrices. The expression of proteolytic enzymes,
      chondrocyte matrix architecture, and matrix degradation parameters was analyzed
      by immunohistochemistry. RESULTS: Of 28 RA explant cultures, 16 displayed an
      invasion of synovial tissue into the cartilage explants, compared with 1 of 8
      osteoarthritis explants. The expression of collagenase and vascular cell adhesion
      molecule 1 could be demonstrated at the cartilage-pannus junction. Of 20
      interactive cell cultures, 18 revealed invasive behavior and remained vital for
      extended periods of time. CONCLUSION: The models presented allow us to study
      distinct aspects of destructive joint diseases under in vitro conditions that
      resemble human pathology. Moreover, our model is able to supplement animal
      experiments in basic research and drug testing.

PMID- 9259422
TI  - Dysregulation of interleukin-10 production in relatives of patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To evaluate interleukin-10 (IL-10) production in relatives of patients
      with systemic lupus erythematosus (SLE). METHODS: Production of IL-10 was
      evaluated in 13 families in which several members had SLE. The constitutive IL-10
      production in SLE patients (n = 16) was compared with that in healthy members of
      these multiplex families (n = 70), in 30 SLE patients who had no relatives with
      SLE, and in 46 healthy unrelated controls. RESULTS: The level of IL-10 production
      did not differ between SLE patients who were members and those who were not
      members of multiplex families (mean +/- SEM 4,384 +/- 908 pg/ml and 4,709 +/- 560
      pg/ml, respectively), but was higher in both groups than in healthy unrelated
      controls (515 +/- 88 pg/ml). The healthy members of the multiplex families
      constitutively produced large amounts of IL-10 (3,080 +/- 311 pg/ml; P < 0.001
      compared with healthy unrelated controls). This high IL-10 production was
      independent of age and sex, and was similar in first- and second-degree relatives
      of SLE patients. The IL-10 was produced both by monocytes and by a subpopulation
      of B lymphocytes in SLE patients and in their relatives. CONCLUSION: The
      dysregulation of IL-10 production previously identified in SLE patients is also
      present in healthy members of families with several cases of SLE, and it may
      contribute to the immunologic abnormalities affecting relatives of SLE patients.

PMID- 9259423
TI  - Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine
      with analogs in vitro and in vivo.
AB  - OBJECTIVE: T cells treated with DNA methylation inhibitors overexpress lymphocyte
      function-associated antigen 1 (LFA-1), which results in autoreactivity, and the
      autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by
      which some agents may cause drug-induced lupus. This study compared the effects
      of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to
      determine if the degree of LFA-1 overexpression and T cell autoreactivity
      correlated with the ability of the agents to induce autoimmunity. METHODS: Cloned
      murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd,
      Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1
      overexpression, autoreactivity, and the ability to induce autoimmunity in vivo.
      RESULTS: Pca and Hyd were more potent than their analogs or HU in all 3 assays.
      CONCLUSION: The results support a relationship between LFA-1 overexpression, T
      cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and
      Hyd, but not the analogs, may cause drug-induced lupus.

PMID- 9259424
TI  - Association of early osteoarthritis of the knee with a Taq I polymorphism of the
      vitamin D receptor gene.
AB  - OBJECTIVE: To determine whether a polymorphism of the vitamin D receptor (VDR)
      gene, already associated with osteoporosis, might also relate to the risk of
      osteoarthritis (OA). METHODS: A population cohort of 351 postmenopausal women
      (ages 45-64 years) was studied using anteroposterior radiographs of the knee,
      which were graded for OA according to the Kellgren and Lawrence classification
      system. The VDR genotype was determined by using polymerase chain reaction and by
      digestion with the restriction enzyme Taq I. RESULTS: The VDR allele "T" was
      associated with an increased risk of knee OA compared with the "t" allele, with
      an odds ratio of 2.82 (95% confidence interval 1.16-6.85; P = 0.02). A dominant
      pattern of risk was suggested. The frequency of the VDR genotype differed
      significantly between OA cases and controls (P = 0.03 by Fisher's exact test).
      CONCLUSION: A Taq I polymorphism of the VDR gene appears to be associated with an
      increased risk of knee OA. This is the first genetic locus that has been shown to
      influence the risk of early knee OA within the general population.

PMID- 9259425
TI  - Collagen crosslinks in fibromyalgia.
AB  - OBJECTIVE: To determine if abnormal collagen metabolism is a characteristic of
      fibromyalgia. METHODS: The diagnosis of fibromyalgia was made according to the
      American College of Rheumatology criteria. Skin biopsy samples were obtained from
      the trapezius region of 8 patients with fibromyalgia. Urine was collected under
      standardized conditions from 55 control subjects and 39 patients with
      fibromyalgia, and serum was obtained from 17 controls and 22 patients with
      fibromyalgia. Pyridinoline (Pyd), an indicator of connective tissue disease, and
      deoxypyridinoline (Dpyd), an indicator of bone degradation, both of which
      represent products of lysyl oxidase-mediated crosslinking in collagen, were
      analyzed by ion-paired and gradient high-performance liquid chromatography (HPLC)
      methods with fluorescence detection. Levels of hydroxyproline (Hyp), a collagen
      turnover marker, were also measured. The findings were related to creatinine
      levels, and the Pyd:Dpyd ratio was determined. RESULTS: Highly ordered cuffs of
      collagen were observed around the terminal nerve fibers by electron microscopic
      examination of biopsy tissue from all 8 patients with fibromyalgia, but were not
      observed in any of the control skin samples. The Pyd:Dpyd ratios in the urine and
      serum and the Hyp levels in the urine were significantly lower in patients with
      fibromyalgia than in healthy controls. CONCLUSION: Decreased levels of collagen
      crosslinking in fibromyalgia may contribute to remodeling of the extracellular
      matrix and collagen deposition around the nerve fibers, and may contribute to the
      lower pain threshold at the tender points. Analysis of altered collagen
      metabolism either by histologic examination on biopsy, or preferably, by HPLC
      analysis of collagen metabolites in urine or serum may aid in understanding more
      about the pathogenesis of fibromyalgia.

PMID- 9259426
TI  - Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine
      kinase receptor axl: potential role in autocrine signaling in cartilage.
AB  - OBJECTIVE: To determine if human articular chondrocytes express the axl tyrosine
      kinase receptor and its ligand Gas-6, a protein product of growth-arrest-specific
      gene 6, and to determine if Gas-6 and axl function in the regulation of
      chondrocyte growth and survival. METHODS: The presence of Gas-6 and axl was
      examined in situ in human articular cartilage by immunohistochemistry and in
      vitro in cell culture studies using primary human chondrocytes and immortalized
      human chondrocytes. The ability of recombinant Gas-6 to mediate adhesion of
      chondrocytes and to stimulate chondrocyte axl phosphorylation was determined.
      Studies of the role of Gas-6 and axl in cell proliferation and survival were also
      performed. RESULTS: Both Gas-6 and axl were detected in cartilage by
      immunohistochemical staining. Gas-6 and axl messenger RNA (mRNA) and protein were
      also detected in cultures of primary and immortalized human chondrocytes.
      Compared with cells cultured in medium containing 10% serum, Gas-6 mRNA levels
      were increased in immortalized chondrocytes cultured in serum-free medium, while
      axl expression decreased. Chondrocytes attached to Gas-6-coated plastic, and the
      attachment was blocked by a soluble Ig fusion protein containing the axl
      extracellular domain. Recombinant human Gas-6 and serum-free conditioned medium
      from primary and immortalized human chondrocyte cultures stimulated chondrocyte
      axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized
      chondrocytes were stimulated with recombinant Gas-6 or when they were made to
      overexpress axl by transfection. Addition of recombinant Gas-6 to serum-free
      medium resulted in increased survival of primary chondrocytes cultured at low
      density in agarose. CONCLUSION: These findings present evidence for an autocrine
      signaling pathway in cartilage involving Gas-6 and the axl tyrosine kinase
      adhesion receptor. Stimulation of axl by Gas-6 may play an important role in the
      control of chondrocyte growth and survival.

PMID- 9259428
TI  - Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis
      in a managed care setting: the importance of drug and surgery costs.
AB  - OBJECTIVE: To describe the frequency and costs of medical services for patients
      with osteoarthritis (OA) or rheumatoid arthritis (RA) in a managed care setting.
      METHODS: Individual utilization records of medical and pharmacy services for OA
      and RA patients were obtained from a group-model health maintenance organization
      (HMO). Estimates were made for costs of drugs and medical services for arthritis
      from July 1, 1993 to June 30, 1994 using Medicare reimbursement schedules and
      average wholesale drug prices. Calculated rates for each population were
      expressed as counts of events or as dollars per person-year. RESULTS: The average
      individual cost rate of arthritis-related care for 365 RA patients was $2,162 per
      year, and the total cost of RA care to the HMO was $703,053. Prescription
      medications accounted for 62% ($436,440) of the total cost of RA care, while
      ambulatory care accounted for 21% ($150,938), and hospital visits accounted for
      16% ($115,674). With regard to 10,101 OA patients, the average individual cost
      rate was $543 per year, and total cost to the HMO was $4,728,425. Hospital care
      accounted for 46% ($2,170,890) of the total cost of OA care, medications
      accounted for 32% ($1,509,637), and ambulatory care accounted for 22%
      ($1,047,898). CONCLUSION: RA care, in the setting of this study, was
      characterized by intensive treatment, especially frequent use of medications that
      were delivered to most patients. Although the cost of RA care per patient was
      high, cost to the managed care provider was relatively low, owing to the rarity
      of RA. OA care tended to be infrequent, and the largest component of cost was
      hospital care for a small proportion of patients (5%). Owing to the greater
      prevalence of OA, care of OA was nearly 7 times more costly to the managed care
      provider than was care of RA.

PMID- 9259427
TI  - Effects of self-care education on the health status of inner-city patients with
      osteoarthritis of the knee.
AB  - OBJECTIVE: To evaluate a concise program of self-care education delivered by an
      arthritis nurse specialist as an adjunct to primary care for inner-city patients
      with knee osteoarthritis (OA). METHODS: An attention-controlled clinical trial;
      211 inner-city patients with knee OA were assigned arbitrarily to education (E)
      or attention-control (AC) conditions. Group E received an individualized 30-60
      minute educational intervention that emphasized nonpharmacologic management of
      joint pain, preservation of function by problem-solving, and practice of
      principles of joint protection. Brief telephone contacts 1 week and 4 weeks later
      monitored and reinforced new self-care activities. Group AC viewed a 20-minute
      standardized public education presentation on arthritis and received followup
      telephone calls (only to encourage continued participation in the study).
      Outcomes included the Health Assessment Questionnaire (HAQ) Disability and
      Discomfort Scales, 10-cm visual analog scales measuring knee pain at rest and
      while walking, and the Quality of Well-Being (QWB) scale. Assessments were made
      at baseline and at 4-month intervals for 1 year. RESULTS: A total of 165 subjects
      (78%) completed all assessments. After control for baseline status, group E had
      significantly lower scores for disability and resting knee pain throughout the
      year of postintervention followup (P < 0.05 for both). Effects were somewhat
      discordant. By 12 months, functional benefits had begun to wane, while the effect
      on resting knee pain had grown. The overall effects of education on walking knee
      pain, overall joint pain (by HAQ), and general health status (by QWB) were not
      significant. CONCLUSION: Self-care education for inner-city patients with knee
      OA, delivered as an adjunct to primary care, was found to result in notable
      preservation of function and control of resting knee pain. The magnitude of the
      observed effects compares well with those of more labor-intensive and time
      consuming intervention models. However, more sustained preservation of function
      and consistent effects on pain may require prolonged, more proactive followup,
      either by the patient educator or by a trained clinical assistant dedicated to
      the task of supporting self-care by patients with knee OA.

PMID- 9259429
TI  - Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large
      multicenter outpatient practice.
AB  - OBJECTIVE: To define the true risk of hydroxychloroquine (HCQ) retinal toxicity
      by studying the largest single group yet evaluated. METHODS: Retrospective chart
      review of all patients in the Kaiser Permanente Medical Care Program, Southern
      California Region, who had HCQ prescriptions filled from 1991 through 1993 (1,556
      patients in 11 medical centers). Of 1,207 charts of patients who took HCQ and had
      documented ophthalmologic examinations, initial screening identified 21 charts
      (1.7%) that indicated possible HCQ toxicity. RESULTS: We identified 1 patient
      with definite toxicity (1 of 1,207; 0.08%) and 5 other patients with
      indeterminate but probable toxicity (5 of 1,207; 0.4%). The incidence of definite
      HCQ retinal toxicity in patients treated with HCQ at <6.5 mg/kg/day was 0.
      CONCLUSION: In HCQ-treated patients whose renal function is normal, routine
      ophthalmic screening is not indicated if the daily dosage is <6.5 mg/kg. In
      patients whose daily dosage is >6.5 mg/kg or who have taken HCQ continuously for
      > 10 years, annual screening may be appropriate.

PMID- 9259430
TI  - Autoantibodies to a nucleolar RNA helicase protein in patients with connective
      tissue diseases.
AB  - OBJECTIVE: An autoantibody to a nucleolar RNA helicase protein (Gu) was recently
      discovered in a patient with gastric antral vascular ectasia or watermelon
      stomach, a disorder that is increasingly being described in systemic sclerosis
      (SSc). The present study was undertaken to determine whether anti-Gu antibodies
      occur in connective tissue diseases (CTD) and, if so, to determine their
      frequencies and any clinical or immunogenetic associations. METHODS: Anti-Gu
      antibodies were determined by Western blotting of glutathione-purified
      glutathione S transferase-Gu fusion proteins against consecutive antinucleolar
      antibody-positive sera (HEp-2 cell substrate) collected over a 5-year period in a
      rheumatology antinuclear antibody (ANA) testing laboratory. RESULTS: Anti-Gu
      antibodies were found in 11 (10%) of 108 antinucleolar antibody-positive sera.
      The subjects with anti-Gu antibodies included 3 of 46 patients with SSc (7%), 3
      of 17 patients with systemic lupus erythematosus (18%), 4 of 9 patients with
      undifferentiated CTD (44%), and 1 healthy relative of an SSc patient. None of the
      anti-Gu-positive patients had any symptoms suggestive of watermelon stomach.
      Increased frequencies of both HLA-DQA1*0501 and DQB1*0301 were found, but only
      DQB1*0301 maintained statistical significance after correction. CONCLUSION: Anti
      Gu (nucleolar RNA helicase) antibodies occur in low frequencies in patients with
      CTDs who have antinucleolar antibodies by ANA testing, but they are not specific
      for SSc or the watermelon stomach lesion.

PMID- 9259432
TI  - Deposition of antibodies to the collagen-like region of C1q in renal glomeruli of
      patients with proliferative lupus glomerulonephritis.
AB  - OBJECTIVE: To determine if antibodies to the collagen-like region of C1q (C1q
      CLR) are present in the glomerular immune deposits of patients with systemic
      lupus erythematosus (SLE). METHODS: Kidney tissues were obtained at autopsy,
      glomeruli were isolated, and glomerular basement membrane fragments were
      prepared. Antibodies were extracted with low pH or with DNase. RESULTS: The
      concentrations of antibodies to C1q-CLR recovered from the glomeruli were > or
      =50-fold higher per unit of IgG than that found in the serum or in the serum and
      interstitial fluid entrained in glomeruli. Antibodies to C1q-CLR were recovered
      from glomeruli of 4 of 5 patients with proliferative glomerulonephritis at
      autopsy. CONCLUSION: This is the first demonstration that antibodies to C1q-CLR
      are deposited and concentrated in the renal glomeruli of patients with SLE. These
      antibodies, thus, have the potential of contributing to the pathogenesis of lupus
      glomerulonephritis.

PMID- 9259431
TI  - Analysis of human T cell and B cell responses against U small nuclear
      ribonucleoprotein 70-kd, B, and D polypeptides among patients with systemic lupus
      erythematosus and mixed connective tissue disease.
AB  - OBJECTIVE: To analyze T and B cell reactivity with U small nuclear RNP (snRNP) 70
      kd, B, and D polypeptides among patients with connective tissue disease (CTD) and
      to examine the functional characteristics of snRNP-reactive T cell clones.
      METHODS: We used an snRNP enzyme-linked immunosorbent assay and immunoblotting to
      characterize antibodies in patients' sera. We used human recombinant fusion
      proteins 70 kd, B, and D to stimulate and clone snRNP-reactive T cells from CTD
      patients. We analyzed the cell surface phenotype, antigenic specificity, and
      cytokine profiles of T cell clones. RESULTS: Patients showed T cell
      responsiveness to snRNP polypeptides that paralleled their autoantibody
      reactivities. A total of 256 clones were generated, and clones were identified
      which were specific for the 70-kd, B, or D polypeptides. Clones expressed a T
      helper cell phenotype, and were found to produce substantial quantities of both
      interleukin-4 (IL-4) and interferon-gamma, and lesser quantities of IL-2 and IL
      6. CONCLUSION: These results show that CTD patients have clonable circulating
      snRNP-reactive T cells that parallel the specificity of snRNP-reactive antibodies
      in their sera. The snRNP-reactive T cells exhibit a helper cell phenotype and
      produce cytokines which are important in B cell help and differentiation.

PMID- 9259433
TI  - Nitric oxide as S-nitrosoproteins in rheumatoid arthritis.
AB  - OBJECTIVE: Nitric oxide (NO) is a free radical involved in inflammation and
      immune reactions. The presence of NO is usually assessed by assaying its
      degradation products, nitrite and nitrate. NO binds to thiol-containing proteins
      to form S-nitrosoproteins (S-NP). The aim of this study was to investigate the
      presence of S-NP, together with nitrite and nitrate, in patients with rheumatoid
      arthritis (RA). METHODS: Forty patients with RA were studied and compared with 24
      patients with osteoarthritis (OA) and 21 control subjects. Fourteen patients were
      treated with 3 consecutive pulses of methylprednisolone for flares of RA. Nitrite
      was measured by the Griess reaction, and nitrate by a spectrophotometric assay
      using nitrate reductase. Spectrofluorometry coupled with the inner filter effect
      was used for the measurement of S-NP. RESULTS: S-NP was detected in all RA
      samples, both in serum and synovial fluid (SF). Serum and articular S-NP
      concentrations were correlated (P < 0.03). In RA, nitrite and S-NP levels were
      higher in SF than in serum; higher SF levels of the 3 compounds were observed in
      RA than in OA. S-NP levels in RA patients decreased significantly (P < 0.03)
      after pulse methylprednisolone treatment, in parallel with the clinical
      improvement. CONCLUSION: S-NP, a biologically active form of NO, was consistently
      present in RA, with higher concentrations within the arthritic joint. S-NP assays
      should be added to nitrite and nitrate assays for the evaluation of NO
      metabolism. S-NP could be a stable storage form of active NO in RA, and its
      measurement could be useful in evaluating pharmacologic interventions that
      modulate NO generation.

PMID- 9259434
TI  - Is knee joint proprioception worse in the arthritic knee versus the unaffected
      knee in unilateral knee osteoarthritis?
AB  - OBJECTIVE: Neuromuscular joint protection requires proprioceptive input and motor
      output. Impairment of proprioception in knee osteoarthritis (OA) may contribute
      to, and/or result from, the disease. If this impairment was exclusively a local
      result of OA, a between-knee difference would be expected in patients with
      unilateral OA (UOA). To explore causal directions, 2 hypotheses were tested: 1)
      proprioception is worse in UOA patients versus elderly controls; 2)
      proprioception is worse in the arthritic knee versus the unaffected knee in UOA
      patients. METHODS: Twenty-eight UOA patients (Kellgren-Lawrence grade > or =2 in
      1 knee and <2 in the other knee) and 29 elderly controls were enrolled. The
      unaffected knee of each UOA patient and both knees of the elderly controls were
      required to meet symptom, examination, and radiographic criteria. Proprioception
      (detection threshold of joint displacement after slow, passive, automated knee
      motion), body mass index, pain, functional status, range of motion, and laxity
      were measured. RESULTS: UOA patients had worse proprioception than did elderly
      controls, in either knee. A between-knee difference was not found in UOA
      patients. CONCLUSION: Impaired proprioception is not exclusively a local result
      of disease in knee OA. The relative importance of impaired proprioception in the
      development and progression of knee OA will require longitudinal study.

PMID- 9259435
TI  - New-onset juvenile dermatomyositis: comparisons with a healthy cohort and
      children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To determine, in a case-control study, if patients with new-onset
      juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset,
      exposure to certain environmental conditions, frequency of familial autoimmune
      diseases, or antibody titers, compared with 2 control groups. METHODS: A
      structured interview with the families of 80 children with juvenile DM, 40
      children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from
      the same geographic area as the children with juvenile DM, was conducted. All
      children's sera were tested for antibody to Toxoplasma gondii, herpes simplex
      virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children
      with juvenile DM had constitutional symptoms 3 months before the disease-onset
      date (P = 0.013 versus control children). Children with JRA had more relatives
      with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did
      children with juvenile DM or healthy children. Among children < or =7 years of
      age, elevated enteroviral titers were more frequent in those with juvenile DM
      (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a
      common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal.
      CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental
      factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased
      in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months
      before the disease-onset date, and young patients have elevated enteroviral
      titers, as do young geographic controls.

PMID- 9259436
TI  - Catastrophic antiphospholipid syndrome: response to repeated plasmapheresis over
      three years.
AB  - The catastrophic antiphospholipid syndrome (CAPS) is rare and usually fatal. In
      this report, we describe an unusual patient who, 31 years after experiencing an
      atypical preeclampsia-eclampsia presentation known today as the HELLP syndrome
      (hemolysis, elevated liver enzymes, and low platelets), developed CAPS, which
      seemed to complicate a diagnosis of primary antiphospholipid syndrome. She
      responded to repeated plasmapheresis over 3 years. Anticoagulants,
      corticosteroids, intravenous gamma globulin, and intravenous cyclophosphamide had
      all failed to halt the progression of CAPS, but repeated plasmapheresis not only
      halted the condition, but it led to the reversal of a leukoencephalopathy. The
      relationship between HELLP syndrome and CAPS is discussed, and possible
      pathogenetic mechanisms that explain the efficacy of repeated plasmapheresis in
      this setting are suggested. It is postulated that perhaps plasmapheresis, through
      removal of cytokines or other mediators, disrupts the interaction between
      phospholipid-protein complexes and endothelial cells. Repeated plasmapheresis
      should be considered in the most refractory cases of CAPS when more conventional
      treatment regimens have failed.

PMID- 9259437
TI  - Alternative splicing of the 5' region of cathepsin B pre-messenger RNA in
      rheumatoid synovial tissue.

PMID- 9259438
TI  - Cognitive function in systemic lupus erythematosus: results of a 5-year
      prospective study.

PMID- 9259439
TI  - Possible concomitant fibromyalgia in systemic lupus erythematosus patients with
      overt central nervous system disease but with cognitive deficits: comment on the
      article by Kozora et al.

PMID- 9259440
TI  - Clinical experience with systemic illness in women with silicone breast implants:
      comment on the editorial by Rose.

PMID- 9259441
TI  - Antifolate effect of methotrexate: comment on the article by Cronstein.

PMID- 9259442
TI  - Importance of guidelines on glucocorticoid-induced osteoporosis: comment on the
      American College of Rheumatology Recommendations for the prevention and treatment
      of glucocorticoid-induced osteoporosis.

PMID- 9259443
TI  - Management of glucocorticoid-induced osteoporosis--first, do no harm: comment on
      the American College of Rheumatology recommendations for the prevention and
      treatment of glucocorticoid-induced osteoporosis.

PMID- 9259444
TI  - Recommendations for exogenous estrogen to prevent glucocorticoid-induced
      osteoporosis in premenopausal women with oligo- or amenorrhea: comment on the
      American College of Rheumatology recommendations for the prevention and treatment
      of glucocorticoid-induced osteoporosis.

PMID- 9259445
TI  - Lack of efficacy of calcitonin in preventing glucocorticoid-induced bone loss:
      comment on the American College of Rheumatology recommendations for the
      prevention and treatment of glucocorticoid-induced osteoporosis.

PMID- 9259446
TI  - Which treatments are effective in preventing and treating glucocorticoid-induced
      bone loss: comment on the American College of Rheumatology recommendations for
      the prevention and treatment of glucocorticoid-induced osteoporosis.

PMID- 9259447
TI  - Measurement of bone density: comment on the American College of Rheumatology
      recommendations for the prevention and treatment of glucocorticoid-induced
      osteoporosis.

PMID- 9259448
TI  - Distal extremity swelling with pitting edema in polymyalgia rheumatica.

PMID- 9259449
TI  - Identification of necrotic cell death by the TUNEL assay in the hypoxic-ischemic
      neonatal rat brain.
AB  - The time course and localization of DNA fragmentation in a neonatal rat model of
      unilateral hypoxia-ischemia were assessed by means of the terminal transferase
      mediated biotin dUTP nick end labeling (TUNEL) assay. TUNEL-positive cells were
      detected in the hemisphere ipsilateral to the ligation immediately after the
      injury and increased to reach a maximum 1-3 days later, then decreasing until day
      10, in parallel with cell death identified by standard histological methods.
      Cells showing any of the different morphologies of chromatin condensation and
      fragmentation were labeled, particularly within the core of the ischemic lesion.
      These results, obtained in a paradigm of necrosis in the immature brain, add to
      previous evidence suggesting that some forms of non-apoptotic DNA fragmentation
      are labeled by the TUNEL assay.

PMID- 9259450
TI  - Effect of capsaicin on substance P and nerve growth factor in adjuvant arthritic
      rats.
AB  - We have investigated the effect of capsaicin pretreatment (50 mg kg(-1) s.c.) on
      substance P, preprotachykinin (PPT) mRNA, and nerve growth factor (NGF), plus its
      high-affinity receptor, trkA, in adult rats with adjuvant arthritis. Twenty one
      days after induction of adjuvant arthritis, sciatic nerve levels of substance P
      were significantly increased whilst there was a small but non-significant
      increase in gamma-PPT mRNA and substance P in L4/L5 dorsal root ganglia (DRG).
      NGF levels in sciatic nerve and foot skin as well as DRG trkA mRNA were unaltered
      after 21 days arthritis suggesting that NGF may not play a role in chronic
      inflammation. Capsaicin treatment of naive rats significantly reduced substance P
      in all tissues and NGF levels in the sciatic nerve. In contrast, gamma-PPT mRNA
      and trkA mRNA expression in DRG were significantly increased after capsaicin
      treatment. The nervous and skin tissues used in this study were harvested from
      the same rats in which we had previously shown that capsaicin pretreatment
      significantly attenuated the severity of arthritis (Cruwys, S.C., Garrett, N.E.
      and Kidd, B.L., Sensory denervation with capsaicin attenuates inflammation and
      nociception in arthritic rats, Neurosci. Lett., 193 (1995) 205-207). Arthritis in
      capsaicin-treated rats had no effect on substance P or NGF levels in any tissue
      when compared with capsaicin-treated control rats, suggesting that
      pharmacological impairment of the sensory nervous system can reduce the severity
      of inflammatory joint disease.

PMID- 9259451
TI  - Nerve growth factor inhibits the expression of nitric oxide synthase in neurones
      in dissociated cultures of rat dorsal root ganglia.
AB  - In dissociated cultures of DRG derived from 15-day-old rats the numbers of
      neurones expressing immunocytochemically detectable quantities of the neuronal
      isoform of nitric oxide synthase (nNOS) was determined and the effects of
      different culture media examined. The availability of NGF in the cultures was
      found to be a critical determinant of nNOS expression. In a serum-rich media
      (SRM) supplemented with NGF, 24% of the neurones expressed nNOS compared with 72%
      in the absence of added NGF and the presence of an antibody to NGF (t-test, P <
      0.0001). Cultures grown in a defined media (DM) developed poorly and many
      neurones died, these cultures also showed poor growth of other cell types.
      Immunostaining for NGF revealed that some of the non-neuronal cells produce NGF
      and that this would be predicted to contribute to the survival of the neurones.
      In cultures in which neurones were dying most of the surviving neurones expressed
      nNOS suggesting it may have a survival promoting function.

PMID- 9259452
TI  - Serotonin and acetylcholine are crucial to maintain hippocampal synapses and
      memory acquisition in rats.
AB  - Treatment with serotonin and acetylcholine depletors reduced the number of
      synapses in the rat hippocampus. Animals that received the drug treatment lost a
      substantial number of synapses and showed an apparent impairment in memory
      acquisition. Although the animals were behaviorally impaired following the
      treatment, spatial memory was nonetheless eventually attained despite the
      disappearance of long-term potentiation. These data suggest that synapses in the
      hippocampus that are normally maintained by serotonin and acetylcholine are
      crucial for normal acquisition of spatial memory. The number of synapses
      maintained by biogenic amines may be a basic mechanism for neurobehavioral
      plasticity.

PMID- 9259453
TI  - Mapping of cortical areas involved in color vision in non-human primates.
AB  - Positron emission tomography (PET) was used to measure changes in the regional
      cerebral blood flow (rCBF) of rhesus monkeys performing visual discrimination
      tasks. In comparison with both position and brightness discrimination tasks, the
      color discrimination task activated the posterior inferior temporal cortex and a
      ventromedial occipital region, which is located along the anterior one-third of
      the calcarine sulcus. In contrast, the position task activated the middle
      temporal area and intraparietal cortex as compared with the color task. These
      results confirm the segregation of visual pathways and delineate the visual areas
      involved in color vision. This approach might bridge the gap between invasive
      studies in animals and functional imaging studies in humans.

PMID- 9259454
TI  - Inhibition of glutamate reuptake potentiates endogenous nitric oxide-facilitated
      dopamine efflux in the rat striatum: an in vivo microdialysis study.
AB  - The current study investigated the effects of the nitric oxide synthase (NOS)
      substrate, N(G)-hydroxy-L-arginine (H-ARG) and the selective glutamate (GLU)
      reuptake inhibitor (2S)-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) on striatal
      dopamine (DA) and glutamate (GLU) efflux in vivo. Concentric microdialysis probes
      were stereotaxically implanted in the anterior-medial striatum of chloral hydrate
      anesthetized rats. Intra-striatal infusion of PDC (200 microM) elevated
      extracellular (EC) DA and GLU levels concurrently over a 10 fraction collecting
      period without affecting EC asparagine levels. Infusion of H-ARG (200 microM) for
      six 20-min fractions, also significantly elevated EC DA levels. In the presence
      of PDC (200 microM), co-perfusion of H-ARG (200 microM) resulted in supra
      additive increases in EC DA levels. The synergistic effect of PDC and H-ARG
      infusion on DA efflux was attenuated by co-infusion of the NOS inhibitor, 7
      nitroindazole (100-200 microM). These results suggest that while both endogenous
      NO and GLU regulate striatal DA efflux via facilitatory influences, enhanced
      glutamatergic tone on striatal NOS-containing neurons may potentiate NO-synthesis
      and subsequently NO-induced DA efflux.

PMID- 9259455
TI  - Apoptotic, injury-induced cell death in cultured mouse murine motor neurons.
AB  - In order to develop in vitro models of CNS injury, astrocytes have been
      mechanically injured in culture to study reactive astrocytosis. However, scratch
      injury models of pure neuronal cultures have not yet been exploited to study
      programmed cell death (PCD). For this study, we examined model motor neurons
      (NSC19 cells) in culture and found time-dependent cell death in proximity (within
      2.5 mm) to a physical scratch injury. Injury-induced cell death was apoptotic
      verified by positively-stained nuclei using both the in situ end-labeling (ISEL)
      procedure and Hoechst 33342. Unexpectedly, cells proximal to the injury site were
      not affected by the injury until 3 days later suggesting that adjacent motor
      neuron loss was dependent on a 'death signal' produced by direct injury to sister
      neurons. 'Executioners' in apoptosis include free radicals, cell cycle kinases
      and cysteine proteases (caspases). Extracellular serine proteases, such as
      thrombin and granzyme B, may activate such intracellular pathways and several
      inhibitors (serpins), such as CrmA, are effective in blocking apoptosis. Since
      protease nexin I (PNI), a serpin homologous with CrmA, prevents apoptosis of
      lumbar motor neurons and is increased after nerve injury, we examined mRNA by RT
      PCR for PNI expression. Of interest, although we were unable to find significant
      levels of PNI message in NSC19 cells, we did detect it in the parent
      neuroblastoma.

PMID- 9259456
TI  - Serotonergic inhibition of phrenic motoneuron activity: an in vitro study in
      neonatal rat.
AB  - In vitro experiments were conducted on neonatal rat brainstem-spinal cord
      preparations to test the hypothesis of an inhibitory modulation of phrenic
      activity by serotonin (5-HT) via non-5-HT2A receptors [Lindsay, A.D. and Feldman,
      J.L., Modulation of respiratory activity of neonatal rat phrenic motoneurones by
      serotonin, J. Physiol., 461 (1993) 213-233]. The changes induced by 5-HT and
      related agents on phrenic root discharges and membrane currents in identified
      phrenic motoneurons were analysed after blockade of spinal 5-HT2A receptors.
      Spinal application of 5-HT1B (but not 5-HT1A) receptor agonists depressed the
      phrenic activity and the effect was prevented by pretreatment with 5-HT1B (but
      not 5-HT1A, 5-HT2A and 5-HT3) receptor antagonists. Results from phrenic
      motoneuron whole cell recordings do not reject a presynaptic location of the 5-HT
      receptors responsible for this depression.

PMID- 9259457
TI  - Autoradiographic localization of [3H]nociceptin binding sites from telencephalic
      to mesencephalic regions of the mouse brain.
AB  - The binding sites of [3H]nociceptin (also named Orphanin FQ), the endogenous
      ligand of the ORL1 (opiate receptor like 1) receptor, were localized in the
      central nervous system of the mouse using an autoradiographic procedure. A high
      density of binding sites was seen in the cerebral cortex, paraventricular nucleus
      of the thalamus, amygdaloid complex, suprachiasmatic nucleus, medial thalamus and
      medial geniculate nucleus. Moderate binding was observed in the nucleus
      accumbens, lateral septum, lateral thalamus, hippocampus, periaqueductal grey
      matter and pons. Finally, low levels of binding were seen in the striatum,
      olfactory tubercle, hypothalamus and substantia nigra. Thus, it appears that the
      ORL1 receptor is particularly abundant in the cerebral cortex and limbic system
      of the mouse brain.

PMID- 9259458
TI  - Low levels of serum ionized magnesium are found in patients early after stroke
      which result in rapid elevation in cytosolic free calcium and spasm in cerebral
      vascular muscle cells.
AB  - Ninety-eight patients admitted to the emergency rooms of three urban hospitals
      with a diagnosis of either ischemic stroke or hemorrhagic stroke exhibited early
      and significant deficits in serum ionized Mg2+ (IMg2+), but not total Mg, as
      measured with a unique Mg2+-sensitive ion-selective electrode. Twenty-five
      percent of these stroke patients exhibited >65% reductions in the mean serum
      IMg2+ found in normal healthy human volunteers or patients admitted for minor
      bruises, cuts or deep lacerations. The stroke patients also demonstrated
      significant elevation in the serum ionized Ca2+ (ICa2+)/IMg2+ ratio, a sign of
      increased vascular tone and cerebrovasospasm. Exposure of primary cultured canine
      cerebral vascular smooth muscle cells to the low concentrations of IMg2+ found in
      the stroke patients, e.g. 0.30-0.48 mM, resulted in rapid and marked elevations
      in cytosolic free calcium ions ([Ca2+]i) as measured with the fluorescent probe,
      fura-2, and digital image analysis. Coincident with the rise in [Ca2+]i, many of
      the cerebral vascular cells went into spasm. Reintroduction of normal
      extracellular Mg2+ ion concentrations failed to either lower the [Ca2+]i overload
      or reverse the rounding-up of the cerebral vascular cells. These results suggest
      that changes in Mg2+ metabolism play important roles in stroke syndromes and in
      the etiology of cerebrovasospasm associated with cerebral hemorrhage.

PMID- 9259459
TI  - Increased expression of cyclin-dependent kinase 5 in induced apoptotic neuron
      death in rat substantia nigra.
AB  - We reported previously that striatal excitotoxic lesion with quinolinic acid of
      rat pups during the first 2 weeks of postnatal life results in loss of
      dopaminergic neurons of the substantia nigra (SN) due to induced apoptosis. Here
      we demonstrate by immunohistochemistry that, following such a lesion, high levels
      of cyclin-dependent kinase 5 (cdk5) protein are present exclusively in apoptotic
      cells over and above basal levels of diffuse axonal staining. Furthermore,
      localization of high levels of cdk5 is associated also with normal developmental
      programmed cell death in the SN and other regions of the central nervous system,
      including the cerebral cortex. These findings suggest a novel role for cdk5
      during neuron apoptosis and may provide insight into mechanisms of loss of
      dopaminergic neurons in Parkinson's disease.

PMID- 9259460
TI  - Effects of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial
      agonist, on recombinant human GABA(A) receptors.
AB  - gamma-Aminobutyric acidA (GABA(A)) gated chloride ion channels were expressed
      from human recombinant cDNA using the baculovirus/Sf-9 insect cell expression
      system. The electrophysiological effects in whole-cell currents of 5-(4
      piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, were
      investigated on GABA(A) receptor complexes of alpha1beta2gamma2S subunits as well
      as a slightly modified construct of alpha1(valine 121)beta2gamma2S subunits. Here
      we report that (1)4-PIOL induces an inward whole-cell current in a concentration
      dependent manner in both alpha1(val 121)beta2gamma2S and alpha1(ile
      121)beta2gamma2S receptor subunit combinations. (2) The 4-PIOL induced whole-cell
      currents were more pronounced in alpha1(val 121)beta2gamma2S than in alpha1(ile
      121)beta2gamma2S receptor subunit combinations. (3) 4-PIOL inhibited GABA-induced
      responses on alpha1(ile 121)beta2gamma2S and alpha1(val 121)beta2gamma2S receptor
      combinations with similar potency.

PMID- 9259461
TI  - Tau protein in the glial cytoplasmic inclusions of multiple system atrophy can be
      distinguished from abnormal tau in Alzheimer's disease.
AB  - The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple
      system atrophy (MSA). These inclusions are in oligodendrocytes, contain
      microtubular structures of 20-30 nm diameter, and can be labelled
      immunohistochemically with antibodies to ubiquitin, alphaB-crystallin, alpha- and
      beta-tubulin, and the microtubule-associated protein tau. GCIs have been compared
      with neuronal inclusions in other neurodegenerative disorders including the
      neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD), which also
      contain tau protein. In order to determine whether the tau protein of GCIs in MSA
      is similar to that observed in AD we used a panel of antibodies to
      phosphorylation-independent (SMI51, TP007, TP70), dephosphorylation-dependent
      (Tau.1), and phosphorylation-dependent antibodies to tau and neurofilaments (AT8,
      AT180, AT270, SMI31, SMI34, RT97, BF10, 8D8). Immunohistochemistry was performed
      on paraffin wax-embedded brain tissue of the cerebellum, brainstem, and frontal
      lobes (Brodmann areas 4/6) of ten clinically and neuropathologically well
      characterised cases of MSA, two cases of AD, and two normal controls. The NFTs of
      the AD cases were labelled with all the phosphorylation-dependent and
      phosphorylation-independent antibodies and with Tau.1 only after treatment with
      alkaline phosphatase. In contrast, GCIs were immunolabelled by the
      phosphorylation-independent antibodies and Tau.1, but not by the phosphorylation
      dependent antibodies. These data demonstrate that the tau in GCIs is different
      from the abnormally phosphorylated tau found in AD and is similar to normal adult
      tau. The mechanism causing the abnormal accumulation of tau in GCIs remains to be
      elucidated.

PMID- 9259462
TI  - Dexamethasone administered into organum vasculosum laminae terminalis of rabbits
      induced antipyresis via inhibiting nitric oxide pathway in situ.
AB  - Direct administration of lipopolysaccharide (LPS) into the organum vasculosum
      laminae terminalis (OVLT) increased the amount of nitric oxide (NO) release and
      inducible NO synthase expression. These increases paralleled the increase in deep
      body temperature in unanesthetized rabbits. Pretreatment with dexamethasone, a
      synthetic glucocorticoid, not only reduced the fever but also attenuated the NO
      release and the inducible NO synthase expression in the OVLT following an intra
      OVLT dose of LPS. The data suggest that steroids such as dexamethasone exert
      their antipyresis by inhibiting the NO pathway in the OVLT of rabbit brain.

PMID- 9259463
TI  - Projections from dorsal raphe nucleus to the periaqueductal grey matter: studies
      in slices of rat midbrain maintained in vitro.
AB  - In coronal slices of rat midbrain localised injections of FluoroGold or DiO into
      the dorsolateral periaqueductal grey matter (PAG) labelled cells retrogradely in
      the dorsal half of the dorsal raphe nucleus (DRN) and the ipsilateral
      ventrolateral PAG. Low intensity electrical stimulation in the dorsolateral PAG
      (22.9 +/- 1.9 microA) evoked antidromic responses in neurones recorded
      intracellularly in the dorsal subnucleus of the DRN. Antidromic responses could
      also be evoked in neurones in the ventral DRN and its wings but only at much
      higher currents (40.9 +/- 2.5 microA) which likely spread to activate axons in
      the ventrolateral PAG that originated from perikarya in the ventral DRN. The
      findings are discussed in relation to modulation of the excitability of the
      aversive system in the dorsolateral PAG by the DRN.

PMID- 9259464
TI  - Primary afferent-evoked synaptic plasticity in deep dorsal horn neurons from
      neonatal rat spinal cord in vitro.
AB  - Whole-cell patch clamp recordings of deep dorsal horn neurons were undertaken in
      'thick' transverse slices to demonstrate plasticity of primary afferent-evoked
      synaptic responses following conditioning stimulation. Synaptic plasticity was
      observed in neurons throughout the age range examined (postnatal days 3-6 and 9
      16) but only long-term depression (LTD) was evocable in older animals (P9-16).
      Both short- and long-latency synaptic responses could undergo long-term
      potentiation (LTP) and LTD suggesting that AMPA/kainate and NMDA receptor-evoked
      responses are modifiable.

PMID- 9259465
TI  - Glutamate affects the development of the thalamofugal visual projection of the
      chick.
AB  - Examination of the thalamofugal visual projections of the chick following
      treatment of the hyperstriatal regions with glutamate was undertaken to
      investigate whether structural change underlies slowed learning known to follow
      such treatment. On the second day after hatching from eggs exposed to light,
      chicks were injected bilaterally with 5 microl of 100 mM glutamate or
      physiological saline. On post-hatching day 8, retrograde fluorescence labelling
      of the thalamofugal projections with True Blue and FluoroGold led to the
      labelling of thalamic cells which project to the visual hyperstriatum. The number
      of contralateral and ipsilateral projections relative to each dye injection site
      was determined. Glutamate prevented the development of the structural asymmetry
      which is present in control chicks. The resultant symmetry of the thalamofugal
      projections in glutamate-treated chicks may cause deficits in visual
      discrimination.

PMID- 9259466
TI  - Efflux of glutamate into the perilymph of the cochlea following transient
      ischemia in the gerbil.
AB  - Using a microdialysis technique followed by an enzyme cycling analysis, we
      measured changes in the glutamate levels in the perilymph of gerbil cochleae
      before, during and after transient ischemic insult. The basal glutamate level in
      perilymph was 0.35 +/- 0.22 pmol/microl. An almost immediate and continuous rise
      in the level of glutamate occurred after the ischemic insult, which advanced even
      further after recirculation; the average concentration was higher than 40
      pmol/microl 55 min after recirculation. The compound action potentials (CAP)
      monitoring the auditory function totally disappeared after ischemic insult.
      However, CAP reappeared after recirculation; the threshold for acoustic
      stimulation was higher than that observed at the pre-ischemic state.

PMID- 9259467
TI  - Antiproliferative activity of KCl contributes to EGF-induced neurite outgrowth in
      PC12 cells.
AB  - Combinations of epidermal growth factor (EGF) and KCl stimulate differentiation
      in PC12 cells, independent of extracellular calcium [Mark et al., Stimulation of
      neurite outgrowth in PC12 cells by EGF and KCl depolarization: a Ca2+-independent
      phenomenon, J. Cell Biol., 130 (1995) 701-710]. Since EGF is a proliferative
      agent that normally does not stimulate differentiation of PC12 cells, we
      hypothesize that KCl plus EGF may cause differentiation because of the anti
      proliferative activity of KCl. Here we report that treatment of PC12 cells with
      KCl plus EGF resulted in a significant decrease in proliferation and DNA
      synthesis compared with cells treated with EGF alone. In addition, KCl
      significantly reduced the EGF-induced expression of cell cycle progression
      factors cdk2, cdk4, cyclin B1 and PCNA. These data suggest that the anti
      proliferative activity of KCl may convert EGF from a proliferative factor to a
      progression factor.

PMID- 9259468
TI  - Middle cerebral artery occlusion alters neurotransmitter activities in
      ipsilateral and contralateral rat brain regions: an ex vivo voltammetric study.
AB  - Differential pulse voltammetry with treated carbon fibre micro-electrodes has
      been successfully employed in in vivo analysis of neurotransmitter release and
      metabolism. This methodology has been now applied to ex vivo preparations (brain
      slices) in order to study diverse neurotransmitter activities in various brain
      regions ipsilateral and controlateral to a middle cerebral artery (MCA) occlusion
      performed in anaesthetised adult male rats. Data demonstrated that significant
      changes of voltammetric ascorbic acid levels related to the ischaemic state were
      monitored within the ipsilateral to MCA occlusion frontal cortex, striatum,
      nucleus accumbens and hippocampus which were the brain area studied. Furthermore,
      it appeared that voltammetric catecholaminergic and 5-hydroxy indolaminergic
      values measured within the nucleus accumbens controlateral to MCA occlusion
      differ significantly from the results monitored with the same technique in brain
      slices obtained from sham rats. In various studies, the brain regions
      contralateral to MCA occlusion are generally considered as control areas,
      however, the present data suggest that the nucleus accumbens contralateral to the
      MCA occlusion side is specifically affected by the ischaemic state.

PMID- 9259469
TI  - Adenosine depresses transmitter release but is not the basis for 'tetanic fade'
      at the neuromuscular junction of the rat.
AB  - It has been suggested that during repetitive neural stimulation adenosine
      accumulates at the neuromuscular junction and the resulting negative feedback
      action of adenosine is the major basis for tetanic fade (decline in action of
      adenosine during repetitive stimulation) This hypothesis was examined at the rat
      neuromuscular junction by examining the effects of blocking adenosine A1
      receptors. Intracellular recording techniques were used to monitor end-plate
      potentials and miniature end-plate potentials. The data suggest that while
      adenosine serves a role in depressing transmitter release, adenosine accumulation
      during brief periods of stimulation is minimal and adenosine is not the cause for
      tetanic fade.

PMID- 9259470
TI  - Nimodipine and nitrendipine inhibit N-type calcium channels in dibutyryl cAMP
      differentiated neuroblastoma x glioma hybrid (NG 108-15) cells.
AB  - The effects of nifedipine, niguldipine, nimodipine and nitrendipine on the high
      K+-induced intracellular Ca2+ ([Ca2+]i) transient in dibutyryl cAMP
      differentiated neuroblastoma x glioma hybrid NG 108-15 cells were studied by
      using the fluorescent Ca2+ indicator fura-2. It was observed that nifedipine at
      the concentration of 50 microM inhibited the high K+-induced [Ca2+]i transient by
      about 60%; niguldipine at the concentration of 10 microM caused a reduction of
      about 65% in the high K+-induced calcium signal and a further increase in the
      concentration up to 50 microM did not result in a significant further reduction
      in the high K+-induced calcium signal. However, on the other hand, nimodipine and
      nitrendipine at 50 microM inhibited almost completely the high K+-induced [Ca2+]i
      transient. Consequently, it was demonstrated in the present study that nimodipine
      and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be
      unique among the dihydropyridines examined in their effects on calcium channels
      in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells,
      whereas nifedipine and niguldipine appear to block mainly L-type calcium
      channels.

PMID- 9259471
TI  - Prolonged intestinal afferent nerve discharge in response to cholecystokinin-58
      compared to cholecystokinin-8 in rats.
AB  - Intestinal afferents are sensitive to cholecystokinin (CCK) octapeptide. However,
      CCK-58 may be a more biologically relevant molecule. Therefore, recordings from
      jejunal mesenteric afferent bundles were secured for extracellular multi-unit
      recording and the responses to CCK-8 and CCK-58 compared. CCK-8 and CCK-58 (i.v.)
      evoked a dose-dependent, devazepide sensitive, increase in afferent nerve
      discharge. Peak discharge frequency was higher for CCK-8 at all doses (P < 0.05).
      However, response duration was more prolonged for CCK-58 (P < 0.05) at 200
      pmol.kg(-1). This resulted in an overall increase in area under the curve of CCK
      58 compared to CCK-8 (P < 0.05). CCK-58 stimulates afferent discharge in a
      different pattern than CCK-8 and, therefore, may have differential biological
      effects.

PMID- 9259472
TI  - Selective M1 muscarinic receptor antagonists disrupt memory consolidation of
      inhibitory avoidance in rats.
AB  - The effect of three different M1 muscarinic antagonists, pirenzepine, biperiden,
      and trihexyphenidyl on memory consolidation was investigated. Rats were trained
      in a one-trial step-through inhibitory avoidance task and injected
      intraperitoneally immediately afterwards, either with pirenzepine, biperiden, or
      trihexyphenidyl (dose range from 0 to 16 mg/kg). The non-selective antimuscarinic
      compound scopolamine, was also administered for comparison. One day later, rats
      were tested for retention. Results show that biperiden, trihexyphenidyl and
      scopolamine produced a dose-dependent impairment of inhibitory avoidance
      consolidation, while pirenzepine had no effect. The amnestic state produced by
      biperiden and trihexyphenidyl was comparable to that observed after the
      administration of scopolamine. These results indicate that the selective blockade
      of the central M1 muscarinic receptors interfere with memory consolidation of
      inhibitory avoidance and suggest that this receptor subtype is critically
      involved in mnemonic functions.

PMID- 9259473
TI  - Destruction of neurokinin-1 receptor expressing cells in vitro and in vivo using
      substance P-saporin in rats.
AB  - Substance P (SP) acts on neurons through the neurokinin-1 (NK-1) receptor.
      Conjugation of SP to the ribosome inactivating protein, saporin (SAP), produces a
      cytotoxin selective for cells that express the NK-1 receptor. SP-SAP cytotoxicity
      was inhibited by pre-treating the toxin to reduce the disulfide bond connecting
      SP to SAP or by pre-incubation with anti-SP antiserum or by SP analog showing
      that SP-SAP acts through binding of the SP moiety to NK-1 receptors. Injection of
      SP-SAP into the striatum selectively destroyed NK-1 receptor expressing
      interneurons. These results show that SP-SAP will be useful for studying the
      function of NK-1 receptor expressing neurons.

PMID- 9259474
TI  - Cerebello-cerebral projections onto the ventral part of the frontal cortex of the
      macaque monkey.
AB  - The cerebellar projections to the ventral part of the frontal cortex were
      investigated in the Japanese monkey (Macaca fuscata). In anesthetized monkeys,
      stimulation of either the lateral or interposed cerebellar nucleus evoked marked
      surface-negative and depth-positive potentials in the face motor area (Mf) and
      the upper part of the ventral premotor area (PMv) on the contralateral side;
      responses were hardly recorded in the lower part of PMv including the areas
      related to the laryngeal movements. Stimulation of the medial cerebellar nucleus
      induced no significant responses in these areas. The results of the combined
      anterograde and retrograde tracing study indicated that the cerebellar nuclei
      projected to Mf and the upper part of PMv mainly through the nucleus ventralis
      posterior lateralis pars oralis and area X of the thalamus, respectively.

PMID- 9259475
TI  - [125I][Tyr14]Orphanin binding to rat brain: evidence for labelling the opioid
      receptor-like 1 (ORL1).
AB  - [125I][Tyr14]Orphanin binds to a number of saturable non-interacting binding
      sites in rat brain cortical membrane preparations, with a density of 510 fmol/mg
      protein and affinity 0.9 nM. This high affinity, saturable [125I][Tyr14]orphanin
      binding was not inhibited by leu-enkephalin and by other ligands for opiate and
      neurotransmitter receptors both in membrane preparations and brain sections. In
      rat brain sections, the highest density of binding was found in the outer and
      medial cortical layers, subiculum, hippocampus and nucleus accumbens;
      intermediate binding densities were found in the inner cortical layer, pontine
      nuclei, thalamus and hypothalamus. Very low specific binding was seen in the
      cerebellum and striatum, according to the described distribution of ORL1
      transcripts. These results suggest that [125I][Tyr14] orphanin binding in rat
      brain occurs to the described ORL1 receptor.

PMID- 9259476
TI  - The dominant role of exogenous or endogenous interleukin-1 beta on expression and
      activity of inducible nitric oxide synthase in rat microvascular brain
      endothelial cells.
AB  - In the brain large amounts of nitric oxide are produced in response to various
      pathological stimuli such as infectious agents, ischemia and trauma. Although it
      is known that endothelial cells can express the inducible isoform of nitric oxide
      synthase (iNOS) upon activation, the impact of different cytokines on iNOS
      expression in rat microvascular endothelial cells remains unclear. We now
      investigated iNOS mRNA expression and enzyme activity in primary cell cultures of
      rat microvascular brain endothelial cells after treatment with the
      proinflammatory cytokines interleukin-1beta (IL-1beta), Tumor necrosis factor
      alpha (TNF-alpha), and interferon-gamma (IFN-gamma) alone or in combination.
      Cells were characterized by immunocytochemistry staining for von-Willebrand
      factor and the rat brain endothelial antigen recognized by monoclonal antibody
      Ox2. iNOS-enzyme activity was determined by measurement of nitrite in the
      supernatants of cell culture using the Griess-reaction. In addition mRNA
      expression was analysed by RT-PCR with iNOS and IL-1beta specific primers. All
      cells in the endothelial cell culture were found to express the antigenic
      phenotype vWF+/Ox2+/Ox43-, thus identifying the cells as rat brain endothelial
      cells of microvascular origin. IL-1beta was the only cytokine that as a single
      stimulus induced iNOS mRNA expression and iNOS-enzyme activity in these
      endothelial cells. All combinations of two cytokines, including that of TNF-alpha
      and IFN-gamma--or the triple combination led to expression of iNOS-mRNA and
      active protein. Cell activation by the combination of TNF-alpha + IFN-gamma led
      to an early expression of IL-1beta by the endothelial cells suggesting iNOS
      induction as a consequence of endogenous IL-1beta production under this
      challenge. The experiments prove that rat brain microvascular endothelial cells
      express iNOS and produce large amounts of NO under inflammatory conditions.
      Furthermore, our results indicate a decisive role of IL-1beta in iNOS expression
      and NO generation.

PMID- 9259477
TI  - Serotonin as a regulator of hypothalamic-pituitary-interrenal activity in teleost
      fish.
AB  - Evidence for the presence of a serotonin1A (5-HT1A) receptor subtype in the
      salmonid fish brain has recently been presented. In the present study the potent
      5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) was
      tested for its effect on plasma cortisol concentrations in rainbow trout
      (Oncorhynchus mykiss). Blood was sampled and 8-OH-DPAT administered through a
      catheter in the dorsal aorta. Thirty minutes after the injection of 40 microg of
      8-OH-DPAT/kg, plasma cortisol levels had increased from 12 to 149 ng/ml,
      whereupon they fell, reaching baseline levels after 4 h. The effect of 1-40
      microg 8-OH-DPAT/kg on plasma cortisol concentrations was dose-dependent. The
      results lends further support to the hypothesis that the brain serotonergic
      system plays a key role in integrating autonomic, behavioral and neuroendocrine
      stress-responses in fish as well as mammals, suggesting that not only the
      structural and biochemical organization, but also the function of the
      serotonergic system has been conserved during vertebrate evolution.

PMID- 9259478
TI  - Plasma extravasation and neuropeptide release in human skin as measured by
      intradermal microdialysis.
AB  - Time course of plasma extravasation in neurogenic inflammation elicited by
      histamine iontophoresis and topical capsaicin application was measured in vivo by
      a modified intradermal microdialysis technique in humans. Single linear
      plasmapheresis fibers were inserted intracutaneously at the volar forearm and
      perfused with Ringer's solution (4 microl/min) with one microdialysis fiber
      located at the planned stimulation site and a second inside the axon reflex area.
      Protein concentration in the dialysate increased by 300% in the histamine wheal
      but no increase was found in the surrounding flare area. There was no protein
      extravasation in the skin treated with capsaicin nor in the surrounding flare
      region. Inside the histamine-induced flare reaction a significant increase of
      calcitonin gene related peptide (CGRP) was found, whereas the increase of
      substance P (SP) was not significant.

PMID- 9259479
TI  - Pre/postnatal dopamine D1 receptor stimulation induces a differential reduction
      of serotonin levels in hippocampus and superior colliculus of puber rats.
AB  - Previous data have shown that through dopamine D1 receptors serotonin and
      dopamine systems could be interdependent during development. In this study, we
      have analysed monoamine and metabolite levels in hippocampus, striatum and
      superior colliculus of puber male rats, which received 10 days of either prenatal
      or early postnatal D1 receptor stimulation with 0.03 mg/kg of the selective
      agonist SKF 38393. This substance induced a differential long-term and
      significant reduction in serotonin (5-HT) and/or 5-hydroxyindoleacetic acid (5
      HIAA) levels, but it was dependent on the developing brain region. Norepinephrine
      (NE) levels were also reduced in superior colliculus, but only after early
      postnatal treatments. These results suggest that an abnormal stimulation of
      dopamine D1 receptors during sensitive stages of ontogeny may alter the
      development of 5-HT fibers innervating hippocampus and superior colliculus.

PMID- 9259480
TI  - NADPH-diaphorase reactivity is reduced in the molecular layer but increased in
      the granular layer of primate cerebellum after prolonged anaesthesia.
AB  - To test if nitric oxide (NO) is involved in modulation of neuronal activity after
      global changes of brain function, nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) reactivity in the cerebellar cortex was compared in monkeys
      maintained under anaesthesia for 24-48 h with others only anaesthetised for
      perfusion. After prolonged anaesthesia, NADPH-d activity was reduced in the
      molecular layer, but increased in the granular layer, with the maintenance of a
      parasagittal patchy organisation of the highly reactive granule cells. Selective
      labelling of NADPH-d in the infraganglionic plexuses deep to a subset of Purkinje
      cell somata was lost in the anaesthetised animals. This differential alteration
      of NADPH-d reactivity suggests that NO may play a role in regulation of neuronal
      and synaptic activity during anaesthesia.

PMID- 9259481
TI  - Altered expression of NPY-Y1 receptors in kainic acid induced epilepsy in rats.
AB  - Kainic acid-induced limbic seizures cause lasting increases in neuropeptide Y
      (NPY) expression in hippocampal granule cells/mossy fibers. The expression of NPY
      Y1 receptors in these neurons were investigated, using in situ hybridization for
      Y1 mRNA and receptor autoradiography with the Y1-specific ligand
      [125I][Pro34]PYY. Six hours after kainic acid-induced seizures, Y1 receptor mRNA
      levels decreased by 80% in granule cells and concomitantly increased (by 75%) in
      CA2 pyramidal neurons. Subsequently, persistent decreases in Y1 mRNA were seen,
      both in the stratum granulosum and in CA2. Changes in mRNA concentrations were
      accompanied by a transient, although non-significant, increase in
      [125I][Pro34]PYY binding in the molecular layer of the dentate gyrus after 4-6 h
      which was succeeded by a lasting decrease in binding which indicates a persistent
      down-regulation of Y1 receptors in hippocampal areas in kainic acid-induced
      epilepsy.

PMID- 9259482
TI  - Motivation-dependent activity in the dorsolateral part of the prefrontal cortex
      in the monkey.
AB  - Field potentials were recorded on self-paced hand and mouth movements with
      implanted electrodes on the surface and at 2.0-3.0 mm depth in respective
      cortical areas in seven monkeys. Surface-negative (s-N), depth-positive (d-P)
      premovement slow potentials were recorded in the prefrontal cortex only when the
      movements were performed with an intense motivation for a reward. Such a
      motivation-dependent activity was mainly obtained in the rostral bank of the
      arcuate sulcus on both sides (except for the inferior limb of the arcuate sulcus
      in the left hemisphere). Three of the seven monkeys were also tasked with visuo
      initiated hand movements. As motivation for reward decreased, s-N, d-P potentials
      at a latency of about 80 ms after stimulus onset became gradually smaller in the
      rostral bank of the arcuate sulcus in the right hemisphere. These facts suggest
      that motivation-dependent activity is represented in the dorsolateral part of the
      prefrontal cortex in monkeys, and that the cortical part is involved in
      motivational functions as well as in cognitive functions.

PMID- 9259483
TI  - Interhemispheric modulation of sensory transmission in the primary somatosensory
      cortex of rats.
AB  - Single unit responses of the primary somatosensory (SI) cortical neurons to the
      stimulation of the forepaw single digit were monitored in anesthetized rats
      before and after subcutaneous injection of lidocaine to an ipsilateral homologous
      receptive field (IHRF). Quantitative determination of the temporal changes of
      afferent sensory transmission was done by analyzing poststimulus time histograms
      of unit responses. Temporary deafferentation to the IHRF induced immediate, but
      reversible suppression of afferent sensory transmission in the SI cortex and this
      suppression lasts up to 35 min post-deafferentation period (during 10-15 min, 
      21.81 +/- 5.9%, P < 0.01). This result suggests that temporary absence of
      afferent inflow from the digit to the SI cortex may exert interhemispheric
      modulation of afferent sensory transmission in the opposite somatosensory cortex
      of anesthetized rats.

PMID- 9259484
TI  - Estrogen differentially modulates nicotine-evoked dopamine release from the
      striatum of male and female rats.
AB  - In the present experiment we examined the effects of an in vitro infusion of
      nicotine (10 microM) upon dopamine release from superfused striatum of castrated
      male and female rats treated or not treated with estrogen. Estrogen exerted
      bidirectional effects on nicotine-evoked dopamine release as a function of the
      sex of the animal. Nicotine-evoked dopamine release was increased in estrogen
      treated females and decreased in estrogen treated males. Peak nicotine-evoked
      dopamine output from estrogen treated females was significantly greater than that
      of estrogen treated males. These results may be related to the gender differences
      in response to nicotine and smoking behavior.

PMID- 9259485
TI  - Peripheral development of cranial nerves in a cyclostome, Lampetra japonica:
      morphological distribution of nerve branches and the vertebrate body plan.
AB  - The development of peripheral nerves was studied in a Japanese marine lamprey,
      Lampetra japonica, in whole-mount and sectioned embryos from hatching until the
      earliest ammocoete. Nerve fibers were immunohistochemically stained with a
      monoclonal antibody against acetylated tubulin. Branchiomeric nerves first
      developed in a simple metamerical pattern, each associated with a single
      pharyngeal arch. Of those, the ophthalmicus profundus, maxillomandibular, and
      facial nerves later developed a highly modified branching pattern, whereas
      postotic nerves were less specialized and showed the stereotypical branching
      pattern of post-trematic nerves. The early distribution of melanocytes in myotome
      free space largely overlapped with the morphology of the cranial nerve and
      ganglion anlage, and resembled the cephalic crest cell distribution pattern in
      the early chick embryo. It was suggested that the cephalic crest cell
      distribution, which is also inhibited by myotomes in the lamprey, would be the
      common basis for branchiomeric nerve patterning. In later development of the
      lamprey embryo, myotomes 1 through 3, which had originated in the postotic
      region, grew rostrally into the preotic region, laterally covering all of the
      branchiomeric nerves. This results in a deep position of the cranial nerves,
      which is not observed in gnathostomes.

PMID- 9259486
TI  - Development of intrinsic connections in cat somatosensory cortex.
AB  - We explored the development of clustered connections in cat somatosensory cortex
      by using intracortical injections of biocytin and carbocyanine dye (DiI).
      Biocytin injections in adults revealed clusters of retrogradely labeled cells,
      affirming earlier reports of the patchy nature of corticocortical connectivity in
      the adult cat somatosensory cortex. On postnatal days (PNDs) 1 and 3, a diffuse
      distribution of axons and labeled cells were found after DiI injections. A
      dramatic rearrangement of connections had taken place by PND 6. Well-defined
      clusters of labeled cells surrounded the injection site. Intercluster zones were
      relatively free of labeled cells and contained few labeled axons. At later ages
      (PNDs 12 and 15), a clear patchy distribution of intrinsic connections was seen.
      We analyzed neuronal clustering by using spatial point process analysis, which
      corroborated our qualitative observations. The density of labeled neurons was
      significantly higher in clusters than in the intercluster zones on PND 6.
      Autocorrelations run on profile plots of optical density values, along paths
      parallel to the edge of the injection sites (reflecting axonal distributions),
      revealed significant periodicity (P < .05; center-to-center approximately 750 pm)
      by PND 6. These data demonstrate that corticocortical connections in cat
      somatosensory cortex develop from a diffuse network at birth, which transforms
      into a patchy network by the end of the 1st postnatal week. This is substantially
      earlier than the development of local circuits in the cat visual cortex and may
      reflect fundamental differences in the organization of the two cortices.

PMID- 9259487
TI  - Projections of the nucleus of the basal optic root in pigeons (Columba livia)
      revealed with biotinylated dextran amine.
AB  - The nucleus of the basal optic root (nBOR) of the accessory optic system is known
      to be involved in the analysis of the visual consequences of self-motion.
      Previous studies have shown that the nBOR in pigeons projects bilaterally to the
      vestibulocerebellum, the inferior olive, the interstitial nucleus of Cajal, and
      the oculomotor complex and projects unilaterally to the ipsilateral pretectal
      nucleus lentiformis mesencephali and the contralateral nBOR. By using the
      anterograde tracer biotinylated dextran amine, we confirmed these projections and
      found (previously unreported) projections to the nucleus Darkshewitsch, the
      nucleus ruber, the mesencephalic reticular formation, and the area ventralis of
      Tsai as well as ipsilateral projections to the central gray, the pontine nuclei,
      the cerebellar nuclei, the vestibular nuclei, the processus
      cerebellovestibularis, and the dorsolateral thalamus. In addition to previous
      studies, which showed a projection to the dorsomedial subdivision of the
      contralateral oculomotor complex, we found terminal labelling in the ventral and
      dorsolateral subdivisions. Individual fibers were reconstructed from serial
      sections, and collaterals to various nuclei were demonstrated. For example,
      collaterals of fibers projecting to the vestibulocerebellum terminated in the
      vestibular or cerebellar nuclei; collaterals of fibers to the inferior olive
      terminated in the pontine nuclei; many individual neurons projected to the
      interstitial nucleus of Cajal, the nucleus Darkshewitsch, and the central gray
      and also projected to the nucleus ruber and the mesencephalic reticular
      formation; collaterals of fibers to the contralateral nucleus of the basal optic
      root terminated in the mesencephalic reticular formation and/or the area
      ventralis of Tsai; neurons projecting to the nucleus lentiformis mesencephali
      also terminated in the dorsolateral thalamus. The consequences of these data for
      understanding the visual control of eye movements, neck movements, posture,
      locomotion, and visual perception are discussed.

PMID- 9259488
TI  - Amygdalo-hypothalamic projections in the lizard Podarcis hispanica: a combined
      anterograde and retrograde tracing study.
AB  - The cells of origin and terminal fields of the amygdalo-hypothalamic projections
      in the lizard Podarcis hispanica were determined by using the anterograde and
      retrograde transport of the tracers, biotinylated dextran amine and horseradish
      peroxidase. The resulting labeling indicated that there was a small projection to
      the preoptic hypothalamus, that arose from the vomeronasal amygdaloid nuclei
      (nucleus sphericus and nucleus of the accessory olfactory tract), and an
      important projection to the rest of the hypothalamus, that was formed by three
      components: medial, lateral, and ventral. The medial projection originated mainly
      in the dorsal amygdaloid division (posterior dorsal ventricular ridge and lateral
      amygdala) and also in the centromedial amygdaloid division (medial amygdala and
      bed nucleus of the stria terminalis). It coursed through the stria terminalis and
      reached mainly the retrochiasmatic area and the ventromedial hypothalamic
      nucleus. The lateral projection originated in the cortical amygdaloid division
      (ventral anterior and ventral posterior amygdala). It coursed via the lateral
      amygdalofugal tract and terminated in the lateral hypothalamic area and the
      lateral tuberomammillary area. The ventral projection originated in the
      centromedial amygdaloid division (in the striato-amygdaloid transition area),
      coursed through the ventral peduncle of the lateral forebrain bundle, and reached
      the lateral posterior hypothalamic nucleus, continuing caudally to the hindbrain.
      Such a pattern of the amygdalo-hypothalamic projections has not been described
      before, and its functional implications in the transfer of multisensory
      information to the hypothalamus are discussed. The possible homologies with the
      amygdalo-hypothalamic projections in mammals and other vertebrates are also
      considered.

PMID- 9259489
TI  - Central innervation of the rat ependyma and subcommissural organ with special
      reference to ascending serotoninergic projections from the raphe nuclei.
AB  - The subcommissural organ (SCO) and the cerebral ependyma receive serotoninergic
      innervation, but little is known about their origin in the raphe nuclei.
      Application of the retrograde tracer cholera toxin subunit B (ChB) in the third
      ventricle resulted in uptake in ependymal axons and backfilling of perikarya in
      the dorsomedian part of the dorsal raphe nucleus, immediately under the caudal
      aqueduct. By using dual staining with antisera against serotonin and ChB, a
      portion of the retrogradely labeled neurons was observed to co-store serotonin.
      Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected into different raphe
      nuclei to fill the neurons in the same areas where the retrogradely labeled
      neurons were found. PHA-L injection in the midline of the dorsal raphe nucleus
      gave rise to ascending axonal processes in the mesencephalic central gray, from
      where they entered the periventricular strata and the third ventricular ependyma.
      In the cerebral ependyma, large numbers of positive fibers were consistently
      found in the ventral part of the lateral ventricles and in the dorsal part of the
      third ventricle. A large number of PHA-L-immunoreactive fibers were observed in
      the hypendymal layer of the lateral part of the SCO. Terminal fibers near the
      ependymal cells were also observed. In all cases, the PHA-L injections labeled
      innervating fibers both within the ependyma and in the SCO, whereas injections
      into the median raphe nucleus or in other raphe nuclei (i.e., the raphe pallidus
      and the raphe pontis) labeled fibers neither in the SCO nor in the ependyma. This
      study shows that a specific group of predominantly serotoninergic neurons
      innervates both the ependyma and the SCO and is probably involved in
      cerebrospinal fluid regulation.

PMID- 9259490
TI  - Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the
      gonadotropin-releasing hormone system: combined tracing and light and electron
      microscopic immunocytochemical studies.
AB  - The timing and occurrence of the preovulatory luteinizing hormone (LH) surge in
      the female rodent are critically dependent on the integrity of the
      suprachiasmatic nucleus (SCN). Destruction of the SCN leads to a cessation of the
      ovarian cycle, whereas implantation of estrogen in ovariectomized rats results in
      daily LH surges. The anatomical substrate for these effects is not known.
      Previous studies involving lesions of the SCN have suggested the presence of a
      direct vasoactive intestinal polypeptide (VIP)-containing pathway to gonadotropin
      releasing hormone (GnRH) neurons. To further investigate the direct connection
      between the SCN and the GnRH system, we have used tract-tracing with the
      anterograde tracer Phaseolus vulgaris-leucoagglutinin (PhaL) in combination with
      an immunocytochemical staining for GnRH in light and electron microscopic
      studies. Small, unilateral PhaL deposits, especially when they were placed in the
      rostral ventrolateral portion of the SCN, revealed a bilateral projection to the
      preoptic area, where PhaL-immunoreactive fibers were regularly found in close
      apposition to GnRH neurons. Ultrastructural studies showed synaptic interaction
      of PhaL-containing fibers with GnRH-immunoreactive (IR) cell bodies, thus
      demonstrating a direct SCN-GnRH connection. Taken together, these data provide
      evidence for the existence of a monosynaptic pathway from the SCN to the GnRH
      system in the hypothalamus of the female rat. We suggest that this pathway may
      contain at least VIP as a putative transmitter and may play a role in the
      circadian regulation of the estrous cycle in the female rat.

PMID- 9259491
TI  - Diverse effects of Purkinje cell loss on deep cerebellar and vestibular nuclei
      neurons in Purkinje cell degeneration mutant mice: a possible compensatory
      mechanism.
AB  - The genetic defect in the Purkinje cell degeneration (PCD) mutant mouse
      completely disrupts the cerebellar corticonuclear connection through intrinsic
      action on the final integrating unit of the cerebellar cortex, the Purkinje cell
      (PC). The postsynaptic target neurons of the PC in the deep cerebellar nuclei
      (DCN) and the vestibular nuclei (VN) are denervated by this PC loss by more than
      two-thirds of their total y-aminobutyric acid (GABA)-ergic innervation. This
      massive disinhibition should be reflected in an increased and thus
      electrophysiologically detectable activity of the respective neurons. To address
      this question, we performed extracellular recordings of PCD mutant and
      corresponding wild-type VN neurons under sinusoidal vestibular stimulation. The
      response amplitudes (neuronal response to sinusoidal rotation) of VN neurons in
      PCD mutant mice showed a decrease rather than the expected increase. The same was
      true for the mean resting rate, whereas the phase relationships were unaffected
      for the most part. This finding is a clear indication of compensatory reactions
      in the VN that substitute quantitatively for the lost PC inhibition. The
      expression of the calcium-binding protein parvalbumin (Parv) is assumed to
      correlate with the physiological activity of neurons, and Parv is localized
      predominantly in inhibitory neurons. Because inhibitory inter- or projecting
      neurons are also largely denervated by the PC loss, Parv immunocytochemistry also
      was performed. In wild-type mice, only very few Parv-immunopositive (Parv+)
      somata were present in the VN, and none were present in the DCN. In PCD mutant
      mice, a substantial number of Parv+ neuronal somata were visible in the VN, and
      even more were visible in the DCN. This increase in Parv+ somata in PCD mutant
      mice is closely related temporally and spatially to the extent of denervation
      caused by the PCD. Parv+ neuronal somata are first visible in the dentate nucleus
      at postnatal day (P) 24 and appear in the other cerebellar and VN up to P29.
      Direct double labeling of Parv and GABA and of Parv and glycine reveals that the
      large majority of Parv + neurons colocalize GABA, glycine, or both inhibitory
      transmitters. These results show that neurons that are postsynaptic to cerebellar
      PC develop diverse physiological and biochemical reactions in the course of
      genetically determined PCD. These mechanisms are likely to contribute to the
      phenotypically mild motor disturbances observed in PCD mutant mice.

PMID- 9259492
TI  - Neurofilament and calcium-binding proteins in the human cingulate cortex.
AB  - Functional imaging studies of the human brain have suggested the involvement of
      the cingulate gyrus in a wide variety of affective, cognitive, motor, and sensory
      functions. These studies highlighted the need for detailed anatomic analyses to
      delineate its many cortical fields more clearly. In the present study,
      neurofilament protein, and the calcium-binding proteins parvalbumin, calbindin,
      and calretinin were used as neurochemical markers to study the differences among
      areas and subareas in the distributions of particular cell types or neuropil
      staining patterns. The most rostral parts of the anterior cingulate cortex were
      marked by a lower density of neurofilament protein-containing neurons, which were
      virtually restricted to layers V and VI. Immunoreactive layer III neurons, in
      contrast, were sparse in the anterior cingulate cortex, and reached maximal
      densities in the posterior cingulate cortex. These neurons were more prevalent in
      dorsal than in ventral portions of the gyrus. Parvalbumin-immunoreactive neurons
      generally had the same distribution. Calbindin- and calretinin-immunoreactive
      nonpyramidal neurons had a more uniform distribution along the gyrus. Calbindin
      immunoreactive pyramidal neurons were more abundant anteriorly than posteriorly,
      and a population of calretinin-immunoreactive pyramidal-like neurons in layer V
      was found largely in the most anterior and ventral portions of the gyrus.
      Neuropil labeling with parvalbumin and calbindin was most dense in layer III of
      the anterior cingulate cortex. In addition, parvalbumin-immunoreactive axonal
      cartridges were most dense in layer V of area 24a. Calretinin immunoreactivity
      showed less regional specificity, with the exception of areas 29 and 30. These
      chemoarchitectonic features may represent cellular reflections of functional
      specializations in distinct domains of the cingulate cortex.

PMID- 9259493
TI  - Ontogeny of electrophysiological properties and dendritic pattern in second-order
      chick vestibular neurons.
AB  - The pattern of development of several subpopulations of second-order vestibular
      neurons was investigated by using intracellular recordings from chicken brain
      slices to define the timing of morphological and electrophysiological changes
      occurring at 3 critical ages. Two embryonic stages, embryonic day 13 (E13) and
      E15-16, and also newborn chicks were selected according to previous anatomical
      findings showing the differentiation of primary vestibular afferents and their
      synapses within a distinctive brainstem vestibular nucleus, the tangential
      nucleus. The responses of these cells to depolarizing and hyperpolarizing current
      pulses and their postsynaptic responses to vestibular nerve stimulation were
      recorded, while simultaneously biocytin was injected for subsequent morphogenetic
      analysis. From this study, developmental schedules of membrane properties,
      synaptic responses, and dendritic differentiation were established for the 2 cell
      populations of the tangential nucleus and other neurons located in the
      surrounding vestibular nuclei. Compared with all other second-order vestibular
      neurons, the principal cells of the tangential nucleus exhibited a distinctive
      schedule. Mainly, this includes their pattern of firing on depolarization, the
      shape and duration of the vestibular-evoked excitatory postsynaptic potential,
      and the time of onset of dendritic outgrowth. In regard to these observations,
      E15-16 appears to be a turning point in principal cell ontogeny, whereas these
      features occur earlier in development for other second-order vestibular neurons.
      These findings, which indicate that the principal cells may have distinct
      membrane properties at specific ages, are discussed in light of their unique
      vestibular innervation and the possible consequences for vestibular signal
      processing.

PMID- 9259495
TI  - Radioactively labelled diethylene triamine penta acetate lung scan in
      Pneumocystis carinii pneumonia and asymptomatic HIV-positive patients.
AB  - The objective of this study is to establish normal ranges for the assessment of
      lung permeability, using 99mTc DTPA (diethylene triamine penta acetate) aerosol
      by measuring the half-time of transfer from the lung in asymptomatic HIV-positive
      patients. Also to audit the use of the test in the clinical management of
      outpatients with symptoms suggestive of Pneumocystis carinii pneumonia (PCP). A
      retrospective analysis of data from outpatients' notes for the audit of
      symptomatic patients, and prospective acquisition of 'normal' data for HIV
      positive asymptomatic patients who were non-smokers and smokers was performed.
      Over a period of 8 years, DTPA scans were performed on 400 asymptomatic HIV
      positive patients (121 non-smokers and 279 smokers) and 188 symptomatic HIV
      positive patients with symptoms suggestive of PCP. A biphasic curve of transfer
      of 99mTc DTPA with a half-time of less than 4 min, was considered diagnostic of
      PCP. The mean half-times (+/-SEM) for asymptomatic non-smokers was 61.4 +/- 3 min
      and for smokers was 21.9 +/- 0.8 min. In the symptomatic patients, 106 were
      treated for PCP and in 97 (91.5%) of these, the transfer was biphasic. Of the
      remaining 82 patients with respiratory pathology other than PCP, 71 (86.6%) had
      normal scans. The results show that smokers may have abnormal baseline scans 16/
      279 (5.7%) and therefore a baseline scan before symptoms should be recorded or a
      higher false positive rate can be expected. The test is however highly sensitive
      for the detection of PCP and allows the attending physician to initiate PCP
      treatment without delay.

PMID- 9259494
TI  - Diagnosis of chronic prostatitis: overview and update.
AB  - Symptoms and signs are unhelpful in the diagnosis of chronic prostatitis which in
      many cases continues to rest on comparison of white cells and organisms in urine
      samples collected before (VB2) and after (VB3) prostatic massage to express
      prostatic secretion (EPS), and particularly in the EPS itself, if this is
      obtained. A series of 195 patients is reviewed, 38 with chronic bacterial
      prostatitis (CBP), 66 with chronic non-bacterial prostatitis (CNBP), 55 with
      prostatodynia, and 31 with a history of recurrent urethritis without prostatitis.
      Demographic characteristics and history of recurrent urethritis were similar in
      all groups indicating that recurrent urethritis alone does not predispose to
      prostatitis. The upper limit of normal for the EPS while cell count was taken as
      1000/mm3 in line with other reports. With this, the upper limit of normal for the
      estimate of white cells by simple microscopy appeared to be about 5/high power
      field (hpf) rather than the figure of 10 often quoted; with the latter figure, a
      number of cases of CNBP would have been missed. All microscopy was undertaken
      with the same microscope using a x 40 objective. Culture results showed a
      predominance of enterococci, and cultural and cytological findings in EPS and VB3
      were comparable. On microscopy, clumping of white cells was associated with
      increased numbers-mentioned previously in the literature but not supported by
      data. Ejaculation just before examination was associated with reduced rather than
      the increased numbers of cells previously reported. Individual investigators
      should assess their own methods in determining upper limits of normal for cells.
      In a separate series of 8 patients with symptoms compatible with prostatitis,
      transrectal ultrasound scanning showed a prostatic cyst; aspiration was
      associated with relief of symptoms. It is concluded that transrectal ultrasound
      scanning (TRUS) should precede prostatic investigation by prostatic massage as
      this may save the prolonged treatment often necessary for prostatitis.

PMID- 9259496
TI  - A longitudinal study of the vaginal flora over a menstrual cycle.
AB  - Healthy female volunteers participated in an anonymous study to monitor vaginal
      flora by taking daily vaginal samples and making a smear for later Gram-staining,
      as well as recording information on genital symptoms, sexual activity,
      contraceptive and bathing practices. A modification of Spiegel's criteria was
      used to categorize the Gram-stained smears, an intermediate category between
      normal flora and bacterial vaginosis (BV) being recognized. Of the 22 volunteers
      who completed the study, one was excluded because of pregnancy. Of the remaining
      21 women, 10 (48%) had a normal flora throughout the study, 4 (19%) had an
      abnormal flora throughout and 7 (33%) had a basically normal flora which
      underwent a change to either an intermediate flora in 5 women or fully developed
      BV in 2 of them. In 5 (71%) of these women the change occurred within the first 9
      days of the cycle. Transient changes in the vaginal microbial flora occurred
      predominantly in the first part of the menstrual cycle which suggests that in
      some women hormonal changes could have a role in the pathogenesis of bacterial
      vaginosis.

PMID- 9259498
TI  - The associations between risk behaviour and reported history of sexually
      transmitted diseases, among young women: a population-based study.
AB  - The aim of this study was to determine the associations between risk behaviour
      and women's reported sexually transmitted diseases (STDs). All the women aged 19,
      21, 23 and 25, residing in a specified housing area, were invited to answer a
      questionnaire regarding their sexual behaviour, smoking and alcohol consumption
      and previous history of STD. Of the 611 women participating, one out of 4 women
      had a history of at least one STD. In an univariate analysis, self-reported STD
      was found to be related to age, having more than 4 lifetime sexual partners,
      having practised intercourse at first date, inconsistent use of condoms, alcohol
      consumption of more than 3 bottles of wine per month and smoking. These factors
      were, however, not independent of each other and when subjected to a multivariate
      logistic regression analysis 2 factors, i.e. the lifetime number of sexual
      partners (more than 4 partners vs one; OR 7.94, (3.41-18.50)) and coitus on first
      date (practised more than once vs never, OR 2.99 (1.55-5.78)) emerged as
      independently associated with a previous STD.

PMID- 9259497
TI  - Sexual networks in Uganda: mixing patterns between a trading town, its rural
      hinterland and a nearby fishing village.
AB  - The study was based in south-west Uganda where significant differences in HIV
      prevalence have been found between urban and rural areas. Longitudinal data
      collected in a diary format was used to determine the extent to which high-risk
      men and women living in a truck stop/trading town had sexual contact with people
      from surrounding rural areas and a nearby fishing village. Study participants
      were 143 men, 75 of whom were resident in the town, 40 in a fishing village and
      28 in rural areas, and 81 women, of whom 47 were resident in the town, 25 in the
      fishing village and 9 in a rural area. During 1687 man weeks the 143 men made
      3149 trips and had 5189 sexual contacts. Ninety-two per cent of these sexual
      contacts occurred in the man's current place of residence and 21% were with a new
      partner. The 81 women participated for 1280 women weeks during which they
      recorded 6378 sexual contacts. Women who lived in the fishing village and the
      rural area had around 90% of their contacts with local men while those who lived
      in the town fell into 3 categories: women who charged a relatively high price for
      commercial sex had only 11% of contacts with men living in the town, while those
      who charged a tenth of the price had 71% of contacts with town men. The small
      number of women who fell into an intermediate category, in terms of price, had
      sexual contact with a wide variety of men. These findings show that there is
      little scope for HIV infection to spread between different residential or
      occupational groups. This may help to explain how large differences in HIV
      seropositivity between neighbouring localities can be maintained for long
      periods, despite considerable social and economic mixing between groups and high
      levels of sexual partner change within groups.

PMID- 9259500
TI  - A pilot study to investigate the treatment of anogenital warts with Topical
      Lithium Succinate cream (8% lithium succinate, 0.05% zinc sulphate).
AB  - The incidence of anogenital warts (condyloma acuminatum) is rapidly increasing
      while there is still no totally satisfactory treatment available. In light of the
      emphasis of experimental approaches toward the prevention of viral replication
      and evidence of the antiviral action of lithium salts it was proposed to
      investigate the efficacy of Topical Lithium Succinate cream (LSC) in the
      treatment of anogenital warts. A total of 101 patients (42 women, 59 men) were
      randomized to receive either active or placebo treatment for a period of 4 weeks.
      Assessment of the number, location, size and area of coverage of the warts was
      made by the clinician at baseline, weeks 2, 4, 6 and 12. Compliance to the study
      protocol following cessation of treatment at week 4 was extremely poor. The high
      drop-out rate after this was felt to invalidate data collected after that point.
      It was therefore decided that the analysis should concentrate on the treatment
      period. Of 101 patients entering the trial 51 received active (30 male and 21
      female) and 50 received placebo (29 male, 21 female). The primary efficacy
      variable was percentage change from baseline in the overall coverage of lesions.
      Over all patients LSC treatment resulted in a reduction of 42% (P<0.02) in the
      overall coverage of lesions. Separate analyses for male and female patients
      showed that for males there was a highly significant reduction in the coverage of
      lesions of 65% (P<0.02). However for females the reduction of 11% was not
      significant. A possible explanation for this difference between the sexes is that
      as many of the lesions in the female patients were internal therefore this could
      lead to difficulty in both application of the cream, and subsequent lesion
      assessment.

PMID- 9259502
TI  - Two cases of oral-to-genital HIV-1 transmission.

PMID- 9259501
TI  - Phase II trial of 13-cis-retinoic acid for poor risk HIV-associated Kaposi's
      sarcoma.
AB  - Fifteen men with HIV-associated Kaposi's sarcoma (KS) and poor risk disease
      according to the TIS staging were enrolled in a phase II trial of oral 13-cis
      retinoic acid. The median CD4 cell count was 95 cells/microl (range 7-260) and 6
      had prior AIDS-defining opportunistic infections. One patient was withdrawn on
      account of cutaneous toxicity. Evaluation was by AIDS Clinical Trials Group
      (ACTG)1 defined assessment. One patient achieved a partial response and remains
      on treatment in partial remission. Thus the overall response rate is 7% (95%
      confidence interval 0-23%). A further 5 patients had stable disease (38%: 95%
      confidence interval 7-64%). The overall low activity, considerable toxicity and
      limited cosmetic benefit even in responding patients limits the value of this
      approach in KS. However, this treatment strategy may be more rewarding in early
      good risk KS.

PMID- 9259499
TI  - High HIV prevalence, low condom use and gender differences in sexual behaviour
      among patients with STD-related complaints at a Nairobi primary health care
      clinic.
AB  - Of 22,274 patients > or = 12 years old attending a Nairobi primary health care
      (PHC) clinic, 1076 (4.8%) had STD-related complaints, of whom 980 underwent
      assessment of risk factors for human immunodeficiency virus (HIV) infection and
      infrequent condom use. Gonorrhoea, chancroid, syphilis seroactivity,
      trichomoniasis, or objective signs of STD were found in 78%, and HIV
      seropositivity in 15% of men and 19% of women. Most women were married, living
      with a spouse; while most men were single, or married, but living separated from
      a spouse. Among married men, last sex was with a female sex worker (FSW) or
      casual partner for 60% not living with a spouse and 26% living with a spouse
      (P<0.005). Two or more partners during the past year were reported by 82% of men
      and 25% of women (P <0.001), and 55% of men and 11% of women reported the last
      partner was high risk. HIV seropositivity among both genders was associated with
      numbers of partners, and among women, with being widowed or divorced. Only 3%
      reported use of a condom with the last partner. Among men whose last sex was with
      a FSW, 74% said the reason for not using a condom was not having one. Thus,
      infrequent condom use, low condom availability, and gender differences in
      behaviour necessitate modifying development policies that separate families; and
      better coordination between family planning, PHC, and AIDS/STD programmes, with
      improved supply, social marketing and community-based distribution of condoms in
      high-risk settings for STD/HIV prevention.

PMID- 9259503
TI  - The occurrence of germ cell malignancies in two patients positive for HIV
      antibodies.

PMID- 9259504
TI  - Massive salivary gland swelling due to primary cytomegalovirus infection in an
      AIDS patient.

PMID- 9259506
TI  - Sources of information on genitourinary medicine clinics.

PMID- 9259505
TI  - Metastatic tufted angioma.

PMID- 9259507
TI  - Mycoplasma genitalium in male urethritis.

PMID- 9259508
TI  - Liver disease in HIV-infected patients: multifactorial or not?

PMID- 9259509
TI  - A spotted fever and melaena: acute HIV seroconversion.

PMID- 9259510
TI  - Microwave CO2 plasma-initiated vapour phase graft polymerization of acrylic acid
      onto polytetrafluoroethylene for immobilization of human thrombomodulin.
AB  - The functionalization of polytetrafluoroethylene (PTFE) for human thrombomodulin
      (hTM) binding has been achieved by CO2 plasma activation and subsequent vapour
      phase graft polymerization of acrylic acid (AA). The PTFE surfaces after CO2
      plasma treatment, AA grafting and hTM immobilization were characterized by
      attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, X
      ray photoelectron spectroscopy (XPS) and electron spin resonance (ESR)
      spectroscopy, as well as by zeta potential and wetting measurements to
      quantitatively control each step of modification. The activity of immobilized hTM
      was estimated by the protein C activation test.

PMID- 9259511
TI  - Long circulating biodegradable poly(phosphazene) nanoparticles surface modified
      with poly(phosphazene)-poly(ethylene oxide) copolymer.
AB  - The biodistribution of biodegradable poly(organo phosphazene) nanoparticles
      surface modified by adsorption of a novel poly(organo phosphazene)-poly(ethylene
      oxide) copolymer with a 5000 M(W) PEO chain (PF-PEO[5000]), following intravenous
      administration in rats and rabbits, is described. The data are compared to the
      biodistribution of poly(organo phosphazene) and poly(lactide-co-glycolide)
      nanoparticles coated with a tetrafunctional copolymer of poly(ethylene oxide)
      poly(propylene oxide) ethylenediamine, commercially available as Poloxamine 908.
      This copolymer has a PEO chain of the same size as the poly(organo phosphazene)
      PEO derivative used. The results in the rat model reveal that poly(organo
      phosphazene) nanoparticles with a Poloxamine 908 coating were mainly captured by
      the liver, although a retardation in clearance from the systemic circulation was
      seen. In contrast, the poly(organo phosphazene) nanoparticles coated with PF
      PEO(5000) showed a prolonged blood circulating profile, with only a small amount
      of the nanoparticles sequestered by the liver. This indicates the importance of
      the nature of both the anchoring group and the particle surface on the biological
      performances of the system. Study of the biodistribution of the PF-PEO(5000)
      coated poly(organo phosphazene) nanoparticles in the rabbit model also indicated
      a prolonged systemic circulation lifetime and reduced liver uptake, whereby a
      significant amount of the administered nanoparticles was targeted to the bone
      marrow.

PMID- 9259513
TI  - Immobilization of invertase in conducting polymer matrices.
AB  - This paper reports a novel approach in the electrode immobilization of an enzyme,
      invertase, by electrochemical polymerization of pyrrole in the presence of
      enzyme. The polypyrrole/invertase and polyamide/polypyrrole/invertase electrodes
      were constructed by the entrapment of enzyme in conducting matrices during
      electrochemical polymerization of pyrrole. This study involves the preparation
      and characterization of polypyrrole/invertase and polyamide/polypyrrole/invertase
      electrodes under conditions compatible with the enzyme. It demonstrates the
      effects of pH and temperature on the properties of enzyme electrode. Enzyme
      leakage tests were carried out during reuse number studies. The preparation of
      enzyme electrodes was done in two different electrolyte/solvent systems. The
      enzyme serves as a sucrose electrode and retains its activity for several months.

PMID- 9259512
TI  - Biodegradable polymeric microparticles for drug delivery and vaccine formulation:
      the surface attachment of hydrophilic species using the concept of poly(ethylene
      glycol) anchoring segments.
AB  - Poly(ethylene glycol)-dextran (PEG-DEX) conjugates have been used as a combined
      stabilizer and surface modifier to produce resorbable poly(DL-lactide-co
      glycolide) (PLG) microparticles by an emulsification/solvent evaporation
      technique. The use of PEG or dextran polymers alone was incapable of producing
      microparticles. Particle size measurements revealed smaller mean particle sizes
      (480 nm) and improved polydispersity when using a 1.2% PEG substituted conjugate
      relative to a 9% substituted material (680 nm). PLG microparticles modified by
      post-adsorbed PEG-DEX conjugates flocculated in 0.01 M salt solutions, whereas
      PLG microparticles prepared using PEG-DEX as a surfactant were stable in at least
      0.5 M NaCl solutions. Surface modification of PLG microparticles was confirmed by
      zeta potential measurements and surface analysis using X-ray photoelectron
      spectroscopy. The presence of surface exposed dextran was confirmed by an
      immunological detection method using a dextran-specific antiserum in an enzyme
      linked immunosorbent assay. The findings support a model in which the PEG
      component of the PEG-DEX conjugate provides an anchor to the microparticle
      surface while the dextran component extends from the particle surface to
      contribute a steric stabilization function. This approach offers opportunities
      for attaching hydrophilic species such as targeting moieties to biodegradable
      microparticles to improve the interaction of drug carriers and vaccines with
      specific tissue sites.

PMID- 9259514
TI  - Fungal mycelia as the source of chitin and polysaccharides and their applications
      as skin substitutes.
AB  - A wovenable skin substitute (Sacchachitin) made from the residue of the fruiting
      body of Ganoderma tsugae was developed in this study. Chemical analysis revealed
      that the treated residue was a copolymer of beta-1,3-glucan (ca 60%) and N
      acetylglucosamine (ca 40%) with a filamental structure of mycelia form, as
      demonstrated by both optical and scanning electron microscopy. The pulp-like
      white residue was then woven into thin, porous sheets 7.0 cm in diameter and 0.1
      0.2 mm in thickness by filtration and lyophilized for use as a skin substitute.
      The wound area produced by dissecting rat skin of full thickness was found to
      almost completely heal on the side covered with Sacchachitin, whereas the control
      side covered with cotton gauge was around 6.0 cm2 on the 28th day. Furthermore,
      the wound healing effects of the chitin sheet from crab shell (Beschitin) and
      Sacchachitin were not found to be significantly different.

PMID- 9259515
TI  - Human osteoblast response in vitro to platelet-derived growth factor and
      transforming growth factor-beta delivered from controlled-release polymer rods.
AB  - The purpose of this work was (1) to develop extrudable ethylene-vinyl acetate
      (EVA) copolymer delivery systems capable of sustained release of bioactive
      proteins and (2) to determine the effect of platelet-derived growth factor (PDGF
      BB) and/or transforming growth factor-beta2 (TGF-beta2) on human osteoblast
      proliferation and differentiation. Human osteoblasts were plated in vitro and
      proliferation and protein synthesis assayed at 48 and 96 h. EVA-PDGF rods
      releasing about 34 ng per ml PDGF per day produced a dramatic early increase in
      osteoblast proliferation and no effect on protein synthesis. EVA-TGF-beta2 rods
      releasing about 23 ng per ml per day increased protein synthesis but had no
      effect on proliferation. PDGF and TGF-beta2 together resulted in moderate
      increases in proliferation and a marked increase in protein synthesis.
      Morphologically, PDGF-treated cells became confluent as early as 48 h, while TGF
      beta2-treated cells formed into nodules. This work shows that (1) it is possible
      to deliver physiological levels of bioactive proteins from an extrudable EVA
      delivery system, and (2) bone cell response is dependent on the sequence and
      timing of delivery. Controlled-release delivery systems which mimic injury
      induced healing cascades may be useful in evaluating the role of various
      molecules in osseous repair.

PMID- 9259516
TI  - Apatite layer-coated titanium for use as bone bonding implants.
AB  - For development of thin bioactive coatings on metal implants, a dense and uniform
      apatite layer was coated onto titanium (Ti) implants in situ by using a new
      biomimetic method, which is composed of apatite nucleation and growth steps in
      simulated body fluid (SBF). Analysis of the coatings by thin film X-ray
      diffraction and scanning electron microscopy-energy dispersive X-ray
      microanalysis (SEM-EMPA) before implantation showed that its characteristics were
      very similar to those of natural bone. The coated and uncoated rectangular plates
      were bilaterally implanted into the tibial proximal metaphyses of rabbits. After
      6, 10 and 25 weeks post-implantation, the bone bonding and bone formation at the
      bone-implant interfaces were evaluated by a detachment test and undecalcified
      histological examination. Mechanical testing in tension showed that the failure
      load of apatite layer-coated Ti implants was significantly higher than that of
      uncoated control at each time period (all P < 0.001). Histologically, it was
      shown that bone was deposited directly onto the apatite coating without any
      intervening soft tissue, while in the paired controls, interpositional soft
      tissue was seen at the bone-implant interface. By SEM-EPMA, a uniform calcium-
      and phosphorus-rich layer was detected between the coated implants and bone, but
      not in uncoated controls at either earlier or later time periods. The results
      indicate that the apatite layer deposited on Ti in situ may significantly
      increase the bone bonding strength by providing a bioactive surface, which allows
      for an early bone apposition to the implant. In addition, the apatite layer
      coated Ti produced by the biomimetic process may fulfil the requirements of
      favourable thin coatings and strong adhesion at the metal-coating interface.

PMID- 9259518
TI  - Photochemical grafting of alpha-propylsulphate-poly(ethylene oxide) on
      polyurethane surfaces and enhanced antithrombogenic potential.
AB  - The aim of this study is the grafting of photoreactive alpha-propylsulphate
      poly(ethylene oxide) (PEO-SO3), one end of which is capped with an azidophenyl
      group, on polyurethane (PU) surfaces via a photochemical technique. The anti
      Factor Xa activity and the platelet adhesion characteristics of the modified PU
      surface were evaluated by a chromogenic assay method and by a flow-controlled
      chamber method, respectively. X-ray photoelectron spectroscopy analysis showed
      that PEO-SO3 was covalently grafted on the PU surface. The grafted surface showed
      anti-Factor Xa activity in the presence of antithrombin III, and significantly
      reduced platelet adhesion characteristics as compared with those of the
      unmodified PU surface. These results suggest that the grafting of PEO-SO3
      improves the antithrombogenicity of PU surfaces.

PMID- 9259517
TI  - Histological and histochemical analyses of acid and alkaline phosphatases around
      hydroxyapatite-coated implants: a time course study in rabbit.
AB  - One of the concerns pertaining to hydroxyapatite (HA)-coated dental implants is
      their possible dissolution over time, with ultimate loss of the implant. HA
      coated dental implants were inserted medially into rabbit femoral articular knee
      joints. The implants were retrieved after 1 week, 1 month, 3 months and 6 months.
      At 1 week, many alkaline phosphatase (ALP)-positive osteoblasts were observed
      near the implant surface. No signs of degradation of the coating were present. At
      1 month, only few ALP-positive osteoblasts were present in the marrow spaces at
      the interface with the coating. Many acid phosphatase (ACP)-positive cells were
      observed near the coating. In many marrow spaces the HA coating was reduced in
      thickness. At 3 months, a further reduction of the thickness of the coating, in
      the areas in contact with marrow spaces, was seen. Many ACP-positive cells were
      present in tight contact with the coating. Few ALP-positive osteoblasts were
      present. At 6 months, in many areas in contact with marrow spaces, the HA coating
      was completely resorbed. The histological and histochemical results seem to point
      to the existence of two types of ACP-positive cells: multinuclear, often in the
      process of phagocytosing HA particles, and mononuclear, with a morphology similar
      to osteoclasts.

PMID- 9259519
TI  - Nuclear medicine imaging in renovascular disease: the nephrologist's view.

PMID- 9259520
TI  - 74 MBq radioiodine 131I does not prevent uptake of therapeutic doses of 131I
      (i.e. it does not cause stunning) in differentiated thyroid cancer.
AB  - Altogether, 147 scintiscans, completed 48-72 h after 74 MBq 131I, were compared
      with scintiscans obtained on average 7.8 days after therapeutic doses of 131I.
      The therapeutic doses ranged from 1100 to just over 7400 MBq. The reasons for the
      investigation were to determine (1) if the diagnostic dose interfered with uptake
      of the therapeutic dose and (2) how often more lesions, or greater extent of
      disease, was seen on the images using the larger therapy dose. The post-treatment
      scan showed less uptake in one region in 2 of the 147 patients (1.4%). The post
      treatment scan showed more lesions in 12 patients (8%). In eight patients, the
      extent of disease, but not the stage of disease, was greater. In four patients,
      the stage of disease was increased, three due to lung uptake on the post
      treatment scan which was not seen on the diagnostic scan and one due to uptake in
      lymph nodes on the post-treatment scan which was not present on the diagnostic
      scan. 74 MBq 131I seldom interferes with subsequent therapy and seldom
      underestimates the extent of thyroid cancer. It would appear to be an appropriate
      dose for diagnostic scintigraphy.

PMID- 9259521
TI  - 201Tl scintigraphy does not allow visualization of the thyroid in euthyroid and
      hyperthyroid patients treated with amiodarone.
AB  - A retrospective study was performed to evaluate the usefulness of thallium
      scintigraphy for visualization of thyroid morphology and function. Moreover,
      applying absolute quantitation, we wished to confirm the qualitatively reduced
      99Tc(m) uptake reported by Wiersinga et al. in both euthyroid and hyperthyroid
      patients treated with amiodarone. Over a period of 2 years (1995-96), 10 patients
      (group A; 2 females, 8 males, mean age 68.6 years, range 61-74 years) receiving
      amiodarone treatment for cardiac arrhythmias for at least 4 months were referred
      for exploration of either hyperthyroidism (n = 4) or for exclusion of parathyroid
      adenoma (n = 6). During the same period, 17 patients (group B; 10 females, 7
      males, mean age 62 years, range 19-91 years) referred for Tc-Tl subtraction
      scintigraphy, and in whom follow-up revealed no thyroid or parathyroid pathology,
      were used as controls. In all patients, thyroid status was assessed by thyroid
      function tests. 201Tl and 99Tc(m) uptake was calculated as a percentage of the
      injected dose, taking account of net injected counts and background and isotope
      decay correction. Original images were scored using a 2-point scoring system (0 =
      poor, 1 = fair or good). Uptake of both 99Tc(m) and 201Tl was significantly
      reduced in group A (99Tc[m]: 0.16 +/- 0.21%; 201Tl: 0.30 +/- 0.21%; mean +/-
      S.D.) compared to group B (99Tc[m]: 1.58 +/- 1.07%; 201Tl: 0.72 +/- 0.37%) (P <
      0.005). The mean relative reduction in 99Tc(m) uptake was more pronounced (90%
      decrease) than that of 201Tl (58% decrease). In group A, the 99Tc(m) and 201Tl
      image quality was poor in 10 of 10 and 8 of 10 patients respectively. In group B,
      the 99Tc(m) and 201Tl image quality was poor in 3 of 17 and 4 of 17 patients
      respectively. The decreased uptake of 201Tl may reflect the inhibitory effect of
      iodides on adenyl cyclase and its stimulation by TSH. In conclusion, the data
      presented confirm the qualitatively reduced pertechnetate uptake reported by
      Wiersinga et al. Furthermore, 201Tl uptake by the thyroid in euthyroid or
      hyperthyroid patients treated with amiodarone is also reduced. Although
      quantitatively less pronounced, it does not allow proper visualization of the
      thyroid.

PMID- 9259522
TI  - Accuracy of a registration procedure for brain SPET and MRI: phantom and
      simulation studies.
AB  - Phantom experiments and simulations were performed to evaluate the significance
      of different error sources in a clinical registration procedure for brain SPET
      and MRI based on external markers. The results from the phantom experiments were
      used to adjust the error model for simulations. In the phantom experiments, 13-14
      external markers were attached to the surface of a three-dimensional brain
      phantom for computing registration. Three internal test markers were used to
      estimate the accuracy of registration. The phantom was imaged with two different
      SPET and MRI devices. The mean root-mean-squared (RMS) residual of the locations
      of the test markers after registration using different combinations of four
      external markers varied from 3.5 +/- 1.0 to 5.2 +/- 1.3 mm depending on the
      imaging equipment and parameters used. The accuracy improved with an increasing
      number of external markers, from 3.2 +/- 0.5 to 4.9 +/- 0.5 mm for 6 markers and
      from 3.1 +/- 0.1 to 4.7 +/- 0.1 mm for 13 markers. In simulations, the external
      markers had an error comparable to the corresponding error in the phantom
      experiments. The error in the test markers was varied independently of that of
      the external markers. When the locating error of the test markers was removed,
      about 2 mm of the residuals of the test markers were found to come from this
      source. When an error comparable to the resolution of the original images (7-10
      mm for SPET, 2 mm for MRI) was included in the test markers, the largest mean RMS
      residual after registration was smaller than the resolution error (8.8 +/- 1.1
      mm). This was due to the accuracy of localization of the external markers and the
      fact that the direction of the error was random for each marker. The size of the
      registration error of an image volume was site-dependent, being minimal near the
      centre of mass of the external markers. When comparing the error with the spatial
      resolution of SPET, it was concluded that the accuracy of registration is not the
      limiting factor in region-of-interest analysis of registered images, provided
      that the design and attachment of the marker system are appropriate.

PMID- 9259523
TI  - Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative
      SPET study with 99Tc(m)-ECD.
AB  - Rett syndrome is a progressive neurological paediatric disorder associated with
      severe mental deficiency, which affects only girls. The aim of this study was to
      determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl
      cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can
      explain the clinical manifestation and progression of the disease. Qualitative
      and quantitative global and regional brain blood flow was evaluated in 12 girls
      with Rett syndrome and compared with an aged-matched reference group of children.
      In comparison with the reference group, SPET revealed a considerable global
      reduction in cerebral perfusion in the groups of girls with Rett syndrome. A
      large statistical difference was noted, which was more evident when comparing the
      control group with girls with stage IV Rett syndrome than girls with stage III
      Rett syndrome. The reduction in cerebral perfusion reflects functional
      disturbance in the brain of children with Rett syndrome. These data confirm that
      99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with
      Rett syndrome that may be associated with brain atrophy, even when magnetic
      resonance imaging appears normal.

PMID- 9259524
TI  - Usefulness of residual fractions of L,L-ethylcysteinate dimer (Neurolite) for the
      preparation of 99Tc(m)-L,L-ethylcysteinate dimer.
AB  - According to the reconstitution instructions for the Neurolite labelling kit, the
      contents of vial A (containing the ligand) is dissolved in 3 ml of saline and 1
      ml of the solution is added to vial B (containing 1 ml of phosphate buffer) to
      which 2 ml of 99Tc(m) generator eluate had previously been added. This implies
      that 2 out of 3 ml of the ligand solution is not used. We have investigated the
      radiochemical purity of 99Tc(m)-ECD reconstituted from fractions of the residual
      solution after storage in a freezer. Fractions of 0.25 ml or 0.5 ml were
      reconstituted with 1.11 GBq or 3.7 GBq 99Tc(m)-pertechnetate, respectively, after
      storage at -20 degrees C for periods ranging from 1 day to 4 weeks. In each test
      situation, except when 0.25 ml fractions were labelled with 3.7 GBq 99Tc(m),
      99Tc(m)-ECD was obtained with a radiochemical purity > 95% up to 6 h after
      reconstitution, as determined using two-strip TLC and reverse-phase HPLC. The
      results demonstrate that residual portions of Neurolite kits can be efficiently
      labelled after fractionation and storage in a freezer.

PMID- 9259525
TI  - Evaluation of 99Tc(m)-ECD as a white blood cell labelling agent.
AB  - 99Tc(m)-ECD is a new agent for perfusion brain imaging. Its brain retention is
      attributed to the enzymatic conversion of lipophilic 99Tc(m)-ECD to polar
      monoacid and diacid derivatives. Based on its proposed mechanism of retention in
      the brain, labelling of white blood cells (WBC) with 99Tc(m)-ECD has been studied
      at our laboratory. A labelling efficiency of 42% was achieved by incubating WBC
      with 99Tc(m)-ECD in phosphate buffered saline medium for 30 min. There was a
      washout of 50% of the radioactivity from the cells in 1 h, which might contribute
      to increased background in potential human studies. However, rapid urinary
      elimination of the radioactivity is expected to deal with this problem due to the
      rapid in vivo conversion of the parent compound to polar metabolites. 99Tc(m)-ECD
      appears to be a promising agent for labelling WBC. Furthermore, already prepared
      multidose 99Tc(m)-ECD may be used for either brain perfusion imaging or WBC
      labelling.

PMID- 9259526
TI  - 99Tc(m)-polyclonal IgG scintigraphy in the detection of infected hip and knee
      prostheses.
AB  - We investigated the usefulness of 99Tc(m)-polyclonal human IgG (99Tc[m]-HIG)
      scintigraphy in the diagnosis of infected hip and knee prostheses. Twenty-nine
      scintigraphic studies were performed in 27 patients (17 females, 10 males) with a
      suspected prosthetic infection. As some patients had bilateral prostheses, a
      total of 35 prostheses were evaluated. There were 25 hip replacements and 10 knee
      prostheses. The images were analysed both visually and quantitatively. The
      scintigraphic results were compared with the culture results of surgical
      specimens and also with clinical follow-up after 3 months. Increased uptake was
      observed in 22 prostheses, of which 12 were true-positive and 10 were false
      positive results. Staphylococci were the agents most commonly isolated. In all
      false-positive patients, aseptic inflammation was diagnosed. Based on
      quantitative analysis, no statistically significant difference was found between
      the true-positive and false-positive cases. For the prostheses as a whole, the
      sensitivity, specificity, positive predictive value and negative predictive value
      were 100%, 41%, 54% and 100% respectively. For the hip prostheses alone, these
      values were 100%, 53%, 57% and 100% respectively. Taking its high sensitivity and
      predictive value into consideration, 99Tc(m)-HIG scintigraphy can be used as a
      screening test to help eliminate prosthetic infection.

PMID- 9259527
TI  - HIDA kinetics in children.
AB  - Quantitative analyses were performed on paediatric HIDA scans (EHIDA and DISIDA)
      to measure the flow rates of HIDA into and out of the liver. Analysis of the
      tracer outflow rate indicated that HIDA appeared to leave the liver even when
      there was complete biliary obstruction, implying 'leakage' from hepatocytes back
      into the blood. This potentially explains why a 'hepatogram' does not provide
      useful information about hepatic obstruction, whereas a renogram does yield
      useful information about renal outflow obstruction. In a small group of patients
      with no evidence of either hepatocellular disease or obstruction, the HIDA inflow
      rate into the liver was 0.003072 s(-1), which is similar to published colloid
      uptake rates in normal livers. This implies that although the two
      radiopharmaceuticals are taken up by different mechanisms, both mechanisms have a
      very similar extraction fraction. Patients with cirrhosis had a considerably
      reduced HIDA uptake rate (0.001072 s[-1]), and once again this was similar to
      colloid uptake from the blood in cirrhosis. Patients investigated for neonatal
      jaundice all showed reduced HIDA inflow, and this reduction was greatest (mean
      0.000477 s[-1]) in those neonates whose jaundice was due to hepatocellular
      impairment. In biliary atresia, the HIDA rate was reduced to approximately
      0.001040 s(-1), which was still considerably higher than the rate from patients
      with neonatal jaundice due to sufficient hepatocellular impairment to cause
      complete cholestasis.

PMID- 9259528
TI  - Renal 99Tc(m)-DMSA SPET and planar imaging: are they really the same?
AB  - Previous studies have suggested that more defects are detected on SPET than on
      planar DMSA images. The aim of this study was to evaluate differences between
      planar and SPET imaging. Sixty-four kidneys from pyelonephritic patients were
      studied using both techniques. An automated algorithm for reorientation and
      centring of the SPET images was used to minimize inter-observer variability.
      Reduced uptake and contour defects showed different localization on planar and
      SPET imaging. Coincidence of defects on both types of image was low. We also
      noted a dependence on defect frequency content for detectability. Image contrast
      played a noticeable role in the detection of defects. Differences in contrast
      between SPET and planar images may be responsible for the variable success in the
      detection of defects. Contour defects are seen more frequently on tomographic
      slices, whereas reduced uptake defects are seen more frequently on planar images.
      A difference is also noted between the cortical and calyceal zones for
      differently contrasted lesions. SPET and planar DMSA images can potentially
      provide a different diagnosis of renal lesions.

PMID- 9259529
TI  - Renal imaging with 99Tc(m)-dextran.
AB  - Significant uptake and retention of 99Tc(m)-dextran (molecular weight: 81,000) in
      renal parenchyma was discovered during evaluation of its intravascular use. Renal
      SPET images confirmed this. This study was designed to evaluate 99Tc(m)-dextran
      as a renal cortex imaging agent. Stability of parenchymal retention was shown by
      insignificant outflow at 24 h and by frusemide intervention. Evaluation of the
      renal parameters of intravenous 99Tc(m)-dextran (n = 71 normal kidneys) and its
      comparison with 99Tc(m)-DTPA n = 10) and 99Tc(m)-DMSA(III) (n = 23) was
      undertaken. The early glomerular extraction phase of the renograms of 99Tc(m)
      DTPA and 99Tc(m)-dextran appeared identical; parenchymal uptake of 99Tc(m)
      dextran continued to increase and reached a near-plateau by 40-60 min. The mean
      cortex-to-background and cortex-to-liver ratios at 2 h with 99Tc(m)-dextran and
      99Tc(m)-DMSA(III) were 14.9 and 9.2, and 16.0 and 8.9, respectively. The target
      to-nontarget ratios were similar despite different absolute renal uptake values
      (12 vs 20% at 2 h) because of faster background clearance of 99Tc(m)-dextran. The
      mechanism of parenchymal retention of 99Tc(m)-dextran appears to be trapping at
      the endothelial-epithelial interphase of the glomerulus. Our initial experience
      suggests 99Tc(m)-dextran is a viable renal parenchyma imaging agent.

PMID- 9259531
TI  - Are MIBI/tetrofosmin heart studies a potential radiation hazard to technologists?
AB  - The number of nuclear medicine studies is increasing and they are becoming more
      complex and time-consuming. In particular, this is true of myocardial perfusion
      investigations. We use a one-day protocol for these studies, utilizing 99Tc(m)
      MIBI or 99Tc(m)-tetrofosmin with tomographic rest images (250 MBq) acquired in
      the morning and exercise images (750 MBq) approximately 4 h later after
      pharmacological stress. Imaging technologists are concerned about continual
      exposure to 1000 MBq 99Tc(m) per study. Radiation doses were measured during rest
      (1.0 microSv, n = 18), exercise (2.5 microSv, n = 18) and stress administration
      (2.0 microSv, n = 16), giving a total dose of 5.5 microSv per combined cardiac
      study. We have previously shown that the average dose per radionuclide study
      (excluding myocardial perfusion studies) is 1.5 microSv. Although 5.5 microSv is
      higher, a technologist is highly unlikely to exceed current dose limits. New EC
      legislation, however, is expected to reduce these limits, which may lead to more
      classified workers. Pregnant technologists should avoid, if possible, combined
      cardiac studies, especially if performing other nuclear medicine duties.

PMID- 9259530
TI  - Effect of an additional atropine injection during dobutamine infusion for
      myocardial SPET.
AB  - The aim of this study was to examine the value of an additional atropine
      injection in patients who do not achieve an adequate heart rate during dobutamine
      infusion for myocardial perfusion SPET (single photon emission tomography).
      Patients undergoing dobutamine myocardial SPET who failed to achieve > or = 85%
      of their age-predicted maximal heart rate at the end of dobutamine infusion (D
      protocol) had a second dobutamine myocardial SPET study on a separate day with
      the addition of an atropine injection during the dobutamine infusion (D + A
      protocol). Twenty-nine patients were studied. 201Tl was used in 27 patients and
      99Tc(m)-MIBI in two patients. All patients underwent coronary angiography and
      significant coronary artery disease was found in 19 of 29 patients. The mean
      heart rate obtained at the peak of dobutamine infusion in the D + A protocol was
      significantly higher than that in the D protocol (153.8 +/- 13.8 vs 117.5 +/-
      15.3 beats min[-1]). The D + A protocol resulted in a higher diagnostic
      sensitivity for the detection of stenosed coronaries compared with the D protocol
      (87 vs 80%, P > 0.05) without changing the specificity (89% for both protocols).
      On the other hand, the frequency of side-effects and ECG changes during the D + A
      protocol was higher than that with the D protocol (32 vs 47). In conclusion, the
      addition of an atropine injection during dobutamine infusion resulted in a higher
      diagnostic sensitivity for identifying stenosed coronaries compared to dobutamine
      alone.

PMID- 9259532
TI  - Reduction of extremity dose in the radiopharmacy.
AB  - With the future introduction of legislation originating from ICRP60 in mind, the
      operating procedures for the radiopharmacy were reviewed, with the intention of
      reducing extremity radiation dose. The radiopharmacist's index fingertip dose was
      measured using TLDs. The radiopharmacist received a mean dose of 0.7 mSv per 10
      GBq of administered activity for the right (non-dominant hand) index finger and
      0.2 mSv per 10 GBq for the left (dominant hand) index finger. These doses were
      comparable with other publications. The radiopharmacist received the largest part
      of the radiation dose during the preparation of 99Tc(m)-MDP. During this
      preparation, the saline was withdrawn into a syringe already containing 99Tc(m)
      eluate, which results in a dose to the fingers. The technique was changed so that
      the saline and 99Tc(m)-eluate were withdrawn and injected separately into a MDP
      kit. This reduced the right finger radiation dose to 0.4 mSv per 10 GBq, while
      the left finger radiation dose remained at 0.2 mSv per 10 GBq. This shows that
      radiation doses can be effectively reduced using simple changes in procedure.

PMID- 9259533
TI  - Radiation dose estimates of 186Re-hydroxyethylidene diphosphonate for palliation
      of metastatic osseous lesions: an animal model study.
AB  - A common complication in patients with breast or prostate cancer is bone
      metastases causing pain. New radionuclide therapy methods have recently been
      proposed for palliation, including 186Re-hydroxyethylidene diphosphonate (186Re
      HEDP). This paper reports on the local development of 186Re-HEDP and the
      biodistribution studied in animals for eventual use in patients. Adult dose was
      computed assuming a 70 kg standard man. The 186Re was labelled to HEDP using
      standard techniques. The biodistribution in five Chacma baboons (Papio ursinus)
      was studied. Doses ranging from 39.4 to 44.9 MBq kg(-1) (mean 43.6 +/- 2.8 MBq
      kg[-1]) were administered, corresponding to an adult human dose of 2960 MBq (80
      mCi). Whole-body images of the animals were obtained with a dual-headed
      scintillation camera on an hourly basis for 6 h post-injection and then daily for
      3 days. The bone, soft tissue, kidneys and urinary bladder were considered source
      organs and data from these organs were used in a compartmental model to obtain
      the mean residence times of the radionuclide in the different source organs.
      Radiation dose estimates for 186Re-HEDP were subsequently obtained with the
      MIRDOSE 3 program. The estimated absorbed radiation doses to some of the organs
      (expressed in mGy MBq[-l]) were as follows: bone surface 1.69; kidneys 0.09;
      liver 0.04; ovaries 0.04; red marrow 0.75; total body 0.12; urinary bladder wall
      0.43. 186Re-HEDP yielded an effective dose of 0.17 mSv MBq(-1). The radiation
      dose delivered to the bone marrow in this study did not cause any detrimental
      effect to the baboons, indicating that locally produced 186Re-HEDP is suitable
      for clinical use.

PMID- 9259534
TI  - To report or not?

PMID- 9259535
TI  - Isolation and labelling of white blood cells.

PMID- 9259537
TI  - Protein secretion: puzzling receptors.
AB  - All known sorting receptors for soluble cargo in the secretory pathway are
      transmembrane proteins. For sorting to the regulated pathway, however, a
      subpopulation of secretory proteins, associated with the membrane but not
      membrane-spanning, appears to link cargo and membrane in storage granule
      biogenesis.

PMID- 9259536
TI  - Antigen presentation: mixing oil and water.
AB  - Studies of the cellular immunology and protein structure of human and mouse CD1
      proteins reveal these to be a family of antigen-presenting molecules that allow T
      cells to recognize lipid and glycolipid antigens of microbial pathogens.

PMID- 9259538
TI  - Cell-cell signalling: frog frizbees.
AB  - The recent discovery that Frizzled proteins are receptor for Wnts has been
      quickly followed by the identification of a secreted protein, Frzb, that is
      related to Frizzled, expressed by the Spemann organizer in frog embryos and can
      bind to and antagonize Wnt developmental signalling molecules.

PMID- 9259539
TI  - Mammalian evolution: an early record bristling with evidence.
AB  - Some shocking revelations in the fossil record--including fossilized hair as well
      as teeth and skeletons--both illuminate and complicate views evolution of ancient
      mammals that lived during, and just after, the age of the dinosaurs.

PMID- 9259540
TI  - Evolution: setting the mutation rate.
AB  - A recent study of X-chromosome and autosome genes in mammals suggests that
      selective trade-offs are important in the long-term evolution of mutation rates;
      but recent studies with bacteria show that high mutation rates can nonetheless
      evolve in the short term in clonal populations.

PMID- 9259541
TI  - Circadian rhythms: PASsing time.
AB  - Links are being discovered between the circadian clock mechanisms in different
      species. The Neurospora Frequency protein has a rhythm of abundance and
      phosphorylation similar to that of the Drosophila Period protein, and Neurospora
      and mouse clock components, like Period, have 'PAS' domains.

PMID- 9259542
TI  - Retinal processing: visionary transgenics.
AB  - Two recent reports in which transgene techniques were used to label specific cell
      classes in the mouse retina have opened the way to new methods of studying
      retinal signal processing.

PMID- 9259543
TI  - Synaptic plasticity: neighborhood influences.
AB  - Recent studies indicate that, when the strengths of specific synapses are
      modified by activity, changes in strengths also occur at neighboring synapses;
      this neighborhood influence has important implications for how synaptic
      modifications implement learning and memory.

PMID- 9259544
TI  - Signalling enzymes: bursting with potential.
AB  - A newly identified form of phosphoinositide 3-kinase is regulated by G beta gamma
      subunits and is particularly abundant in phagocytic leukocytes. It is likely to
      be intimately involved in the process by which inflammatory signals regulate
      phagocyte activation and is a potential target for new anti-inflammatory drugs.

PMID- 9259545
TI  - DNA repair: RAD alert.
AB  - Mammalian homologues of two important yeast genes involved in DNA double-strand
      break repair and recombination, RAD51 and RAD54, have been isolated. Knock-out
      mutations of the genes in mice reveal both reassuring similarities to, and
      surprising differences from, the analogous mutant phenotypes in yeast.

PMID- 9259546
TI  - Prebiotic evolution: selecting for homochirality before RNA.
AB  - Recent results show that the self-assembly of long homochiral oligomers of a
      nucleotide analogue can be achieved by ligation of short oligomers of chirally
      mixed composition. Do these results show how the RNA world might have arisen?

PMID- 9259547
TI  - RNA processing: pocket guides to ribosomal RNA.
AB  - The functional role of a recently identified class of small nucleolar (sno) RNAs
      has been elucidated: the 'box H/ACA' snoRNAs act as guide RNAs, specifying the
      position of evolutionarily conserved pseudouridines in ribosomal (r)RNA via an
      rRNA-snoRNA base-pairing interaction that forms a 'pseudouridine pocket'.

PMID- 9259548
TI  - Growth control: action mouse.
AB  - A recently described knockout mouse has abnormally large muscles. The phenotype
      suggests that the ablated product, growth differentiation factor 8 or
      'myostatin', may be one of the long sought inhibitors that control the growth of
      individual tissues and organs.

PMID- 9259549
TI  - Transcriptional control: calling in histone deacetylase.
AB  - Mad proteins are transcriptional repressors that antagonize transcriptional
      activation and transformation by Myc oncoprotein; recent findings suggest that
      they repress transcription by recruiting histone deacetylases to target sites on
      DNA.

PMID- 9259550
TI  - Calcium release and influx colocalize to the endoplasmic reticulum.
AB  - Intracellular Ca2+ is released from intracellular stores in the endoplasmic
      reticulum (ER) in response to the second messenger inositol (1,4,5) trisphosphate
      (InsP3) [1,2]. Then, a poorly understood cellular mechanism, termed capacitative
      Ca2+ entry, is activated [3,4]; this permits Ca2+ to enter cells through Ca(2+)
      selective Ca(2+)-release-activated ion channels [5,6] as well as through less
      selective store-operated channels [7]. The level of stored Ca2+ is sensed by
      Ca(2+)-permeant channels in the plasma membrane, but the identity of these
      channels, and the link between them and Ca2+ stores, remain unknown. It has been
      argued that either a diffusible second messenger (Ca2+ influx factor; CIF) [8] or
      a physical link [9,10] connects the ER Ca(2+)-release channel and store-operated
      channels; strong evidence for either mechanism is lacking, however [7,10].
      Petersen and Berridge [11] showed that activation of the lysophosphatidic acid
      receptor in a restricted region of the oocyte membrane results in stimulation of
      Ca2+ influx only in that region, and concluded that a diffusible messenger was
      unlikely. To investigate the relationship between ER stores and Ca2+ influx, we
      used centrifugation to redistribute into specific layers the organelles inside
      intact Xenopus laevis oocytes, and used laser scanning confocal microscopy with
      the two-photon technique to 'uncage' InsP3 while recording intracellular Ca2+
      concentration. Ca2+ release was localized to the stratified ER layer and Ca2+
      entry to regions of the membrane directly adjacent to this layer. We conclude
      that Ca2+ depletion and entry colocalize to the ER and that the mechanism linking
      Ca2+ stores to Ca2+ entry is similarly locally constrained.

PMID- 9259551
TI  - Inhibition of receptor-mediated endocytosis by the amphiphysin SH3 domain.
AB  - BACKGROUND: Receptor-mediated endocytosis appears to require the GTP-binding
      protein dynamin, but the process by which dynamin is recruited to clathrin-coated
      pits remains unclear. Dynamin contains several proline-rich clusters that bind to
      Src homology 3 (SH3) domains, which are short modules found in many signalling
      proteins and which mediate protein-protein interactions. Amphiphysin, a protein
      that is highly expressed in the brain, interacts with dynamin in vitro, as do
      Grb2 and many other SH3 domain-containing proteins. In this study, we examined
      the role of amphiphysin in receptor-mediated endocytosis in vivo. RESULTS: To
      address the importance of the amphiphysin SH3 domain in dynamin recruitment, we
      used a transferrin and epidermal growth factor (EGF) uptake assay in COS-7
      fibroblasts. Amphiphysin is present in these cells at a low level and indeed in
      other peripheral tissues. Confocal immunofluorescence revealed that cells
      transfected with the amphiphysin SH3 domain showed a potent blockade in receptor
      mediated endocytosis. To test whether the cellular target of amphiphysin is
      dynamin, COS-7 cells were contransfected with both dynamin and the amphiphysin
      SH3 domain; here, transferrin uptake was efficiently rescued. Importantly, the
      SH3 domains of Grb2, phospholipase C gamma and spectrin all failed to exert any
      effect on endocytosis. The mechanism of amphiphysin action in recruiting dynamin
      was additionally tested in vitro: amphiphysin could associate with both dynamin
      and alpha-adaptin simultaneously, further supporting a role for amphiphysin in
      endocytosis. CONCLUSIONS: Our results suggest that the SH3 domain of amphiphysin
      recruits dynamin to coated pits in vivo, probably via plasma membrane adaptor
      complexes. We propose that amphiphysin is not only required for synaptic-vesicle
      endocytosis, but might also be a key player in dynamin recruitment in all cells
      undergoing receptor-mediated endocytosis.

PMID- 9259552
TI  - Mammalian homologues of C. elegans PAR-1 are asymmetrically localized in
      epithelial cells and may influence their polarity.
AB  - The establishment of polarity in the embryo is fundamental for the correct
      development of an organism [1]. The first cleavage of the Caenorhabditis elegans
      embryo is asymmetric with certain cytoplasmic components being distributed
      unequally between the daughter cells [2-4]. Using a genetic screen, Kemphues and
      co-workers have identified six par genes (partition-defective) [5,6], which are
      involved in the process of asymmetric division. One of these genes encodes a
      highly conserved protein, PAR-1, which is a serine/threonine kinase that
      localizes asymmetrically to the posterior part of the zygote and to those
      blastocysts that give rise to the germ line [7-9]. We reasoned that the mammalian
      homologue of PAR-1 (mPAR-1) might be involved in the process of polarization of
      epithelial cells, which consist of apical and basolateral membrane domains. We
      found that mPAR-1 was expressed in a wide variety of epithelial tissues and cell
      lines and was associated with the cellular cortex. In polarized epithelial cells,
      mPAR-1 was asymmetrically localized to the lateral domain. A fusion protein
      lacking the kinase domain had the same localization as the full-length protein
      but its prolonged expression acted in a dominant-negative fashion: lateral
      adhesion of the transfected cells to neighbouring cells was diminished, resulting
      in the former cells being 'squeezed out' from the monolayer. Moreover, the
      polarity of these cells was disturbed resulting in mislocalization of E-cadherin.
      Thus, in the C. elegans embryo and in epithelial cells, polarity appears to be
      governed by similar mechanisms.

PMID- 9259553
TI  - UNIFOLIATA regulates leaf and flower morphogenesis in pea.
AB  - BACKGROUND: The vegetative phenotype of the pea mutant unifoliata (uni) is a
      simplification of the wild-type compound leaf to a single leaflet. Mutant uni
      plants are also self-sterile and the flowers resemble known floral meristem and
      organ identity mutants. In Antirrhinum and Arabidopsis, mutations in the floral
      meristem identity gene FLORICAULA/LEAFY (FLO/LFY) affect flower development
      alone, whereas the tobacco FLO/LFY homologue, NFL, is expressed in vegetative
      tissues, suggesting that NFL specifies determinacy in the progenitor cells for
      both flowers and leaves. In this paper, we characterised the pea homologue of
      FLO/LFY. RESULTS: The pea cDNA homologue of FLO/LFY, PEAFLO, mapped to the uni
      locus in recombinant-inbred mapping populations and markers based on PEAFLO
      cosegregated with uni in segregating sibling populations. The characterisation of
      two spontaneous uni mutant alleles, one containing a deletion and the other a
      point mutation in the PEAFLO coding sequences, predicted that PEAFLO corresponds
      to UNI and that the mutant vegetative phenotype was conferred by the defective
      PEAFLO gene. CONCLUSIONS: The uni mutant demonstrates that there are shared
      regulatory processes in the morphogenesis of leaves and flowers and that floral
      meristem identity genes have an extended role in plant development. Pleiotropic
      regulatory genes such as UNI support the hypothesis that leaves and flowers
      derive from a common ancestral sporophyll-like structure. The regulation of
      indeterminancy during leaf and flower morphogenesis by UNI may reflect a
      primitive function for the gene in the pre-angiosperm era.

PMID- 9259554
TI  - Virulence and hyphal formation of Candida albicans require the Ste20p-like
      protein kinase CaCla4p.
AB  - BACKGROUND: The pathogenic fungus Candida albicans is capable of a morphological
      transition from a unicellular budding yeast to a filamentous form. Extensive
      filamentous growth leads to the formation of mycelia displaying hyphae with
      branches and lateral buds. Hyphae have been observed to adhere to and invade host
      tissues more readily than the yeast form, suggesting that filamentous growth may
      contribute to the virulence of this major human pathogen. A molecular and genetic
      understanding of the potential role of morphological switching in the
      pathogenicity of C. albicans would be of significant benefit in view of the
      increasing incidence of candidiasis. RESULTS: The CaCLA4 gene of C. albicans was
      cloned by functional complementation of the growth defect of cells of the budding
      yeast Saccharomyces cerevisiae deleted for the STE20 gene and the CLA4 gene.
      CaCLA4 encodes a member of the Ste20p family of serine/threonine protein kinases
      and is characterized by a pleckstrin homology domain and a Cdc42p-binding domain
      in its amino-terminal non-catalytic region. Deletion of both alleles of CaCLA4 in
      C. albicans caused defects in hyphal formation in vitro, in both synthetic liquid
      and solid media, and in vivo in a mouse model for systemic candidiasis. The gene
      deletions reduced colonization of the kidneys in infected mice and suppressed C.
      albicans virulence in the mouse model. CONCLUSIONS: Our results demonstrate that
      the function of the CaCla4p protein kinase is essential for virulence and
      morphological switching of C. albicans in a mouse model. Thus, hyphal formation
      of C. albicans mediated by CaCla4p may contribute to the pathogenicity of this
      dimorphic fungus, suggesting that regulators of morphological switching may be
      useful targets for antifungal drugs.

PMID- 9259555
TI  - The prohibitin family of mitochondrial proteins regulate replicative lifespan.
AB  - Cellular senescence is determined by multiple factors, including the genetic
      regulation of metabolism and responses to endogenous and exogenous stresses [1
      4]. Recent studies implicate a limited number of gene products in elongating
      lifespan in yeast and Caenorhabditis elegans [2-4]; these include the C, elegans
      gene cik-1, a central regulator of metabolism [5], and yeast RAS2, which controls
      the response to ultraviolet irradiation and other stresses [3]. Another gene
      postulated to effect senescence is PHB1, the yeast homologue of prohibitin [3], a
      rodent gene initially identified as a potential regulator of growth arrest and
      tumour suppressor [6-8]. Highly conserved prohibitin homologues have been
      identified in mammals [9], Drosophila [10], C. elegans [9], plants [11] and
      yeast. A second mammalian gene, encoding BAP37, a protein with sequence
      similarity to prohibitin, is thought to be involved in lymphocyte function [9].
      Here, we show that the nuclear-encoded mammalian prohibitin and BAP37 proteins
      are present in mitochondria, are co-expressed, and interact physically with each
      other. Deletion of the Saccharomyces cerevisiae homologues, PHB1 and PHB2,
      results in a decreased replicative lifespan and a defect in mitochondrial
      membrane potential. Our observations highlight the relationship between the
      metabolic efficiency of cells and the ageing process, and provide evidence for
      its evolutionary conservation.

PMID- 9259556
TI  - Evolution of the entire arthropod Hox gene set predated the origin and radiation
      of the onychophoran/arthropod clade.
AB  - BACKGROUND: Dramatic changes in body size and pattern occurred during the
      radiation of many taxa in the Cambrian, and these changes are best documented for
      the arthropods. The sudden appearance of such diverse body plans raises the
      fundamental question of when the genes and the developmental control systems that
      regulate these designs evolved. As Hox genes regulate arthropod body patterns,
      the evolution of these genes may have played a role in the origin and
      diversification of the arthropod body plan from a homonomous ancestor. To trace
      the origin of arthropod Hox genes, we examined their distribution in a myriapod
      and in the Onychophora, a sister group to the arthropods. RESULTS: Despite the
      limited segmental diversity within myriapods and Onychophora, all insect Hox
      genes are present in both taxa, including the trunk Hox genes Ultrabithorax and
      abdominal-A as well as an ortholog of the fushi tarazu gene. Comparative analysis
      of Hox gene deployment revealed that the anterior boundary of expression of trunk
      Hox genes has shifted dramatically along the anteroposterior axis between
      Onychophora and different arthropod classes. Furthermore, we found that
      repression of expression of the Hox target gene Distal-less is unique to the
      insect lineage. CONCLUSIONS: A complete arthropod Hox gene family existed in the
      ancestor of the onychophoran/arthropod clade. No new Hox genes were therefore
      required to catalyze the arthropod radiation; instead, arthropod body-plan
      diversity arose through changes in the regulation of Hox genes and their
      downstream targets.

PMID- 9259557
TI  - The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate
      targeted migration of branchial neural crest cells.
AB  - BACKGROUND: During vertebrate head development, neural crest cells migrate from
      hindbrain segments to specific branchial arches, where they differentiate into
      distinct patterns of skeletal structures. The rostrocaudal identity of branchial
      neural crest cells appears to be specified prior to migration, so it is important
      that they are targeted to the correct destination. In Xenopus embryos, branchial
      neural crest cells segregate into four streams that are adjacent during early
      stages of migration. It is not known what restricts the intermingling of these
      migrating cell populations and targets them to specific branchial arches. Here,
      we investigated the role of Eph receptors and ephrins-mediators of cell-contact
      dependent interactions that have been implicated in neuronal pathfinding-in this
      targeted migration. RESULTS: Xenopus EphA4 and EphB1 are expressed in migrating
      neural crest cells and mesoderm of the third arch, and third plus fourth arches,
      respectively. The ephrin-B2 ligand, which interacts with these receptors, is
      expressed in the adjacent second arch neural crest and mesoderm. Using truncated
      receptors, we show that the inhibition of EphA4/EphB1 function leads to abnormal
      migration of third arch neural crest cells into second and fourth arch
      territories. Furthermore, ectopic activation of these receptors by overexpression
      of ephrin-B2 leads to scattering of third arch neural crest cells into adjacent
      regions. Similar disruptions occur when the expression of ephrin-B2 or truncated
      receptors is targeted to the neural crest. CONCLUSIONS: These data indicate that
      the complementary expression of EphA4/EphB1 receptors and ephrin-B2 is involved
      in restricting the intermingling of third and second arch neural crest and in
      targeting third arch neural crest to the correct destination. Together with
      previous work showing that Eph receptors and ligands mediate neuronal growth cone
      repulsion, our findings suggest that similar mechanisms are used for neural crest
      and axon pathfinding.

PMID- 9259558
TI  - MARCKS regulates membrane ruffling and cell spreading.
AB  - The dynamic rearrangement of the actin cytoskeleton is fundamental to most
      biological processes including embryogenesis, morphogenesis, cell movement, wound
      healing and metastasis [1]. Membrane ruffling and reversible cell-substratum
      interactions underlie actin-driven cell movement. Protein kinase C (PKC)
      stimulates membrane ruffling and adhesion [2], but the mechanism by which this
      occurs is unknown. Myristoylated alaninerich C kinase substrate (MARCKS) is a PKC
      substrate that cycles on and off membranes by a mechanism termed the myristoyl
      electrostatic switch [3-6]. While at the membrane, MARCKS binds to and sequesters
      acidic phospholipids including phosphatidyl-inositol-4,5-bisphosphate (PIP2) [7].
      MARCKS also binds and cross-links filamentous actin, an activity which is
      regulated by PKC-dependent phosphorylation and calcium-calmodulin [3]. In this
      report, we demonstrate that expression, in fibroblasts, of MARCKS containing a
      mutation which abrogates the myristoyl-electrostatic switch prevents cell
      spreading. The MARCKS mutant arrests the cell during an early stage of spreading,
      characterized by profuse membrane blebbing, and prevents the formation of
      membrane ruffles and lamellae usually found at the leading edge of spreading
      cells. This defect in the regulation of the actin cytoskeleton is accompanied by
      a decrease in cell-substratum adhesion. Our results provide direct evidence that
      MARCKS and PKC regulate actin-dependent membrane ruffling and cell adhesion,
      perhaps via a PIP2-dependent mechanism.

PMID- 9259559
TI  - A new human gene complex encoding the killer cell inhibitory receptors and
      related monocyte/macrophage receptors.

PMID- 9259560
TI  - Interactions of Eph-related receptors and ligands confer rostrocaudal pattern to
      trunk neural crest migration.
AB  - BACKGROUND: In the trunk of avian embryos, neural crest migration through the
      somites is segmental, with neural crest cells entering the rostral half of each
      somitic sclerotome but avoiding the caudal half. Little is known about the
      molecular nature of the cues-intrinsic to the somites-that are responsible for
      this segmental migration of neural crest cells. RESULTS: We demonstrate that Eph
      related receptor tyrosine kinases and their ligands are essential for the
      segmental migration of avian trunk neural crest cells through the somites. EphB3
      localizes to the rostral half-sclerotome, including the neural crest, and the
      ligand ephrin-B1 has a complementary pattern of expression in the caudal half
      sclerotome. To test the functional significance of this striking asymmetry,
      soluble ligand ephrin-B1 was added to interfere with receptor function in either
      whole trunk explants or neural crest cells cultured on alternating stripes of
      ephrin-B1 versus fibronection. Neural crest cells in vitro avoided migrating on
      lanes of immobilized ephrin-B1; the addition of soluble ephrin-B1 blocked this
      inhibition. Similarly, in whole trunk explants, the metameric pattern of neural
      crest migration was disrupted by addition of soluble ephrin-B1, allowing entry of
      neural crest cells into caudal portions of the sclerotome. CONCLUSIONS: Both in
      vivo and in vitro, the addition of soluble ephrin-B1 results in a loss of the
      metameric migratory pattern and a disorganization of neural crest cell movement.
      These results demonstrate that Eph-family receptor tyrosine kinases and their
      transmembrane ligands are involved in interactions between neural crest and
      sclerotomal cells, mediating an inhibitory activity necessary to constrain neural
      precursors to specific territories in the developing nervous system.

PMID- 9259562
TI  - The seven deadly curs'd sins ellipsis Ire.

PMID- 9259561
TI  - Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase
      IV.
AB  - BACKGROUND: Mammalian cells deficient in the XRCC4 DNA repair protein are
      impaired in DNA double-strand break repair and are consequently hypersensitive to
      ionising radiation. These cells are also defective in site-specific V(D)J
      recombination, a process that generates the diversity of antigen receptor genes
      in the developing immune system. These features are shared by cells lacking
      components of the DNA-dependent protein kinase (DNA-PK). Although the XRCC4 gene
      has been cloned, the function(s) of XRCC4 in DNA end-joining has remained
      elusive. RESULTS: We found that XRCC4 is a nuclear phosphoprotein and was an
      effective substrate in vitro for DNA-PK. Human XRCC4 associated extremely tightly
      with another protein(s) even in the presence of 1 M NaCl. Co-immunoprecipitation
      and adenylylation assays demonstrated that this associated factor was the
      recently identified human DNA ligase IV. Consistent with this, XRCC4 and DNA
      ligase IV copurified exclusively and virtually quantitatively over a variety of
      chromatographic steps. Protein mapping studies revealed that XRCC4 interacted
      with ligase IV via the unique carboxy-terminal ligase IV extension that comprises
      two tandem BRCT (BRCA1 carboxyl terminus) homology motifs, which are also found
      in other DNA repair-associated factors and in the breast cancer susceptibility
      protein BRCA1. CONCLUSIONS: Our findings provide a function for the carboxy
      terminal region of ligase IV and suggest that BRCT domains of other proteins may
      mediate contacts between DNA repair components. In addition, our data implicate
      mammalian ligase IV in V(D)J recombination and the repair of radiation-induced
      DNA damage, and provide a model for the potentiation of these processes by XRCC4.

PMID- 9259563
TI  - JZ Young 1907 - 1997.

PMID- 9259564
TI  - A chiming biological clock?

PMID- 9259565
TI  - Journal journalism.

PMID- 9259566
TI  - First steps into the signalling maze.

PMID- 9259568
TI  - Science with a punch.

PMID- 9259567
TI  - The job search.

PMID- 9259569
TI  - The sum of the parts.

PMID- 9259570
TI  - Widespread eukaryotic sequences, highly similar to bacterial DNA polymerase I,
      looking for functions.

PMID- 9259571
TI  - Barth syndrome may be due to an acyltransferase deficiency.

PMID- 9259572
TI  - Ecology of Helicobacter pylori in the human stomach.

PMID- 9259573
TI  - Simultaneous expression of Borrelia OspA and OspC and IgM response in
      cerebrospinal fluid in early neurologic Lyme disease.
AB  - Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi
      (Bb). Neurological involvement is common in all stages. In vivo expression of Bb
      antigens (Ags) and the immune response to them has not been well investigated in
      the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and
      concomitant downregulation of OspA before tick inoculation of the spirochete has
      been reported in skin and blood in animals. CSF OspA Ag in early disease suggests
      otherwise in CSF. Early Ag expression and IgM response in human CSF was
      investigated here. Paired CSF and serum was collected from 16 early,
      predominantly erythema migrans Lyme disease patients with neurologic problems, 13
      late Lyme disease patients, and 19 other neurologic disease (OND) controls.
      Samples were examined for IgM reactivity to recombinant Bb-specific Osps using
      ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic
      involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n
      = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16
      (75%) of these early Lyme disease patients with neurologic involvement had CSF
      and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and
      none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF,
      OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme
      disease patients with neurologic involvement. This biologic finding may also
      provide a discriminating marker for CNS infection in Lyme disease.

PMID- 9259574
TI  - Adenovector-mediated gene transfer of active transforming growth factor-beta1
      induces prolonged severe fibrosis in rat lung.
AB  - Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of
      fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and
      studies demonstrating increased expression of total TGF-beta1 in fibrotic tissues
      from a variety of organs. The precise role in vivo of this cytokine in both its
      latent and active forms, however, remains unclear. Using replication-deficient
      adenovirus vectors to transfer the cDNA of porcine TGF-beta1 to rat lung, we have
      been able to study the effect of TGF-beta1 protein in the respiratory tract
      directly. We have demonstrated that transient overexpression of active, but not
      latent, TGF-beta1 resulted in prolonged and severe interstitial and pleural
      fibrosis characterized by extensive deposition of the extracellular matrix (ECM)
      proteins collagen, fibronectin, and elastin, and by emergence of cells with the
      myofibroblast phenotype. These results illustrate the role of TGF-beta1 and the
      importance of its activation in the pulmonary fibrotic process, and suggest that
      targeting active TGF-beta1 and steps involved in TGF-beta1 activation are likely
      to be valuable antifibrogenic therapeutic strategies. This new and versatile
      model of pulmonary fibrosis can be used to study such therapies.

PMID- 9259576
TI  - Extraglomerular origin of the mesangial cell after injury. A new role of the
      juxtaglomerular apparatus.
AB  - We investigated the origin of the glomerular mesangial cell, a smooth muscle-like
      cell that provides structural support in the glomerulus. Injection of anti-Thy 1
      antibody that binds the Thy 1 antigen on rat mesangial cells eliminated (> 95%)
      the mesangial population at 20-28 h, while Thy 1-positive cells in the
      juxtaglomerular apparatus (JGA) were sequestered from the circulation and
      survived. Single pulse labeling with [3H]thymidine at 36 h labeled Thy 1-positive
      cells in the JGA and hilus. Serial biopsies demonstrated the progressive
      migration (5-15 micron/d) and proliferation of these mesangial reserve cells
      until the entire glomerulus was repopulated. The regenerating mesangial
      population expressed contractile and migratory proteins preferentially at the
      leading edge of the migratory front. Single as well as multiple pulse labeling
      with [3H]thymidine confirmed that the entire mesangial cell repopulation
      originated from only a few mesangial reserve cells. These reserve cells resided
      in the extraglomerular mesangium in the JGA and were not renin-secreting cells,
      macrophages, smooth muscle cells, or endothelial cells. These studies document
      mesangial cell migration in the anti-Thy 1 model of mesangial proliferative
      glomerulonephritis and provide evidence for a new role for the juxtaglomerular
      apparatus in the maintenance of the mesangial cell population.

PMID- 9259575
TI  - Intact insulin stimulation of skeletal muscle blood flow, its heterogeneity and
      redistribution, but not of glucose uptake in non-insulin-dependent diabetes
      mellitus.
AB  - We tested the hypothesis that defects in insulin stimulation of skeletal muscle
      blood flow, flow dispersion, and coupling between flow and glucose uptake
      contribute to insulin resistance of glucose uptake in non-insulin-dependent
      diabetes mellitus (NIDDM). We used positron emission tomography combined with
      [15O]H2O and [18F]-2-deoxy--glucose and a Bayesian iterative reconstruction
      algorithm to quantitate mean muscle blood flow, flow heterogeneity, and their
      relationship to glucose uptake under normoglycemic hyperinsulinemic conditions in
      10 men with NIDDM (HbA1c 8.1+/-0.5%, age 43+/-2 yr, BMI 27.3+/-0.7 kg/m2) and in
      7 matched normal men. In patients with NIDDM, rates of whole body (35+/-3 vs.
      44+/-3 micromol/kg body weight.min, P < 0.05) and femoral muscle (71+/-6 vs. 96+/
      7 micromol/kg muscle.min, P < 0.02) glucose uptake were significantly decreased.
      Insulin increased mean muscle blood flow similarly in both groups, from 1.9+/-0.3
      to 2.8+/-0.4 ml/100 g muscle.min in the patients with NIDDM, P < 0.01, and from
      2.3+/-0.3 to 3.0+/-0.3 ml/100 g muscle.min in the normal subjects, P < 0.02.
      Pixel-by-pixel analysis of flow images revealed marked spatial heterogeneity of
      blood flow. In both groups, insulin increased absolute but not relative
      dispersion of flow, and insulin-stimulated but not basal blood flow colocalized
      with glucose uptake. These data provide the first evidence for physiological flow
      heterogeneity in human skeletal muscle, and demonstrate that insulin increases
      absolute but not relative dispersion of flow. Furthermore, insulin redirects flow
      to areas where it stimulates glucose uptake. In patients with NIDDM, these novel
      actions of insulin are intact, implying that muscle insulin resistance can be
      attributed to impaired cellular glucose uptake.

PMID- 9259577
TI  - A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.
AB  - The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly
      expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1,
      the gene has been inactivated in embryonic stem cells by homologous
      recombination. The homozygous mutant mice were viable. These mice developed
      megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the
      ganglia revealed that the enteric neurons hyperinnervated in the narrow segment
      of megacolon. Some of these neuronal cells degenerated and neuronal cell death
      occurred in later stages. We propose that Ncx/Hox11L.1 is required for
      maintenance of proper functions of the enteric nervous system. These mutant mice
      can be used to elucidate a novel pathogenesis for human neuronal intestinal
      dysplasia.

PMID- 9259578
TI  - Somatic deletion of the imprinted 11p15 region in sporadic persistent
      hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous
      hyperplasia and endorses partial pancreatectomy.
AB  - Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or
      nesidioblastosis is a heterogeneous disorder characterized by profound
      hypoglycemia due to inappropriate hypersecretion of insulin. An important
      diagnostic goal is to distinguish patients with a focal hyperplasia of islet
      cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets
      (DiPHHI) because management strategies differ significantly. 16 infants with
      sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were
      investigated. Selective pancreatic venous sampling coupled with peroperative
      surgical examination and analysis of extemporaneous frozen sections allowed us to
      identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases
      of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles
      of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the
      pancreas but not in normal pancreatic cells. This somatic event is consistent
      with a proliferative monoclonal lesion. It involves disruption of the balance
      between monoallelic expression of several maternally and paternally expressed
      genes. Thus, we provide the first molecular explanation of the heterogeneity of
      sporadic forms of PHHI such that it is possible to perform only partial
      pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic
      diabetes in patients with focal adenomatous hyperplasia.

PMID- 9259579
TI  - Contribution of androgens to the gender difference in leptin production in obese
      children and adolescents.
AB  - Recent studies demonstrated significantly higher serum leptin concentrations in
      females as compared with males, even after correction for differences in body fat
      mass. The aim of our study was to measure serum leptin concentrations in a large
      group of obese children and adolescents to determine the possible role of sex
      steroid hormones on both leptin serum concentrations and production in human
      adipocytes. Obese girls were found to have significantly higher leptin
      concentrations than boys at the same degree of adiposity (25.2+/-14.1 vs. 17.2+/
      12.6 ng/ml, P < 0.001). In a multiple regression analysis with age and body mass
      index (percent body fat) as fixed variables, it turned out that testosterone had
      a potent negative effect on serum leptin in boys, but not in girls. In vitro
      experiments using newly developed human adipocytes in primary culture showed that
      both testosterone and its biologically active metabolite dihydrotestosterone are
      able to reduce leptin secretion into the culture medium by up to 62%. Using a
      semiquantitative reverse transcriptase-PCR method, testosterone was found to
      suppress leptin mRNA to a similar extent. These results suggest that, apart from
      differences in body fat mass, the higher androgen concentrations in obese boys
      are responsible for the lower leptin serum concentrations compared with obese
      girls.

PMID- 9259580
TI  - Association of angiotensinogen gene T235 variant with progression of immunoglobin
      A nephropathy in Caucasian patients.
AB  - Genetic variability in the renin-angiotensin system may modify renal responses to
      injury and disease progression. We examined whether the M235T polymorphism of the
      angiotensinogen (AGT) gene, the insertion/deletion polymorphism of the
      angiotensin-converting enzyme (ACE) gene, and the A1166--> C polymorphism of the
      angiotensin II type 1 receptor gene may be associated with disease progression in
      168 Caucasian patients with IgA nephropathy. All patients had serial measurements
      of their creatinine clearance, proteinuria, and blood pressure (mean+/-SD) with a
      follow-up of 6.1+/-4.7 yr. The genotype frequencies for each gene were consistent
      with Hardy-Weinberg equilibrium, and were similar to those of 100 Caucasian
      control subjects. We examined two primary outcomes: (a) the rate of deterioration
      of Ccr, and (b) the maximal level of proteinuria. We found that patients with the
      AGT MT (n = 79) and TT (n = 29) genotypes had a faster rate of deterioration of
      Ccr than those with the MM (n = 60) genotype (i.e., median values, -6.6 and -6.2
      vs. -3. 0 ml/min/yr, respectively; P = 0.01 by Kruskal-Wallis test). Similarly,
      patients with AGT MT and TT genotypes had higher maximal values of proteinuria
      than those with the MM genotype (i.e., median values, 2.5 and 3.5 vs. 2.0 g/d,
      respectively; P < 0.02 by Kruskal-Wallis test). Neither the ACE
      insertion/deletion nor angiotensin II type I A1166--> C gene polymorphism was
      associated with disease progression or proteinuria in univariate analysis.
      Multivariant analysis, however, detected an interaction between the AGT and ACE
      gene polymorphisms with the presence of ACE/DD polymorphism adversely affecting
      disease progression only in patients with the AGT/MM genotype (P = 0.008).
      Neither of these gene polymorphisms was associated with systemic hypertension.
      Our results suggest that polymorphisms at the AGT and ACE gene loci are important
      markers for predicting progression to chronic renal failure in Caucasian patients
      with IgA nephropathy.

PMID- 9259582
TI  - Interferon gamma and interleukin 4 stimulate prolonged expression of inducible
      nitric oxide synthase in human airway epithelium through synthesis of soluble
      mediators.
AB  - Human respiratory epithelium expresses inducible nitric oxide synthase (iNOS)
      continuously in vivo, however mechanisms responsible for maintenance of
      expression are not known. We show that IFNgamma is sufficient for induction of
      iNOS in primary human airway epithelial cells (HAEC) in vitro, and IL-4
      potentiates IFNgamma-induced iNOS expression in HAEC through stabilization of
      iNOS mRNA. IFNgamma/IL-4- induced iNOS expression in HAEC was delayed in onset
      and prolonged with expression up to 1 wk. Removal of overlying culture media
      resulted in loss of expression, while transfer of conditioned media induced iNOS
      mRNA in other HAEC. IFNgamma and IL-4 stimulation activated STAT1 and STAT6 in
      HAEC, but conditioned media transfer to HAEC produced even higher levels of STAT1
      activation than achieved by direct addition of cytokines. Although cytokine
      induction of iNOS was dependent on new protein synthesis, conditioned media
      induction of iNOS in HAEC was not. Further, removal of overlying culture media
      from cells at different times after cytokine stimulation demonstrated that
      mediator synthesis and/or secretion important for induction and maintenance of
      iNOS occurs early after cytokine stimulation. In conclusion, a combination of
      IFNgamma/ IL-4, which occurs naturally in the lung epithelial lining fluid, leads
      to maintenance of iNOS expression in human airway epithelium through production
      of soluble mediators and stabilization of mRNA.

PMID- 9259581
TI  - Significant reduction of the antiatherogenic effect of estrogen by long-term
      inhibition of nitric oxide synthesis in cholesterol-clamped rabbits.
AB  - The purpose of this study was to investigate whether endothelium-derived nitric
      oxide (NO) is involved in the plasma lipid-independent antiatherogenic effect of
      estrogen and levormeloxifene, a partial estrogen receptor agonist. 85 rabbits
      were ovariectomized and balloon-injured in the middle thoracic aorta. The rabbits
      were fed a cholesterol-enriched diet supplemented with 17beta-estradiol,
      levormeloxifene, or placebo, either alone, or together with 160 microg/ml NG
      nitro- -arginine methyl ester (-NAME), an NO synthase inhibitor, in their
      drinking water for 12 wk. Plasma cholesterol was maintained at 25-30 mmol/liter
      by individualized cholesterol feeding. In the undamaged aorta, the extent of
      atherosclerosis in the estrogen group was only one-third that in the placebo
      group. Simultaneous administration of -NAME, however, significantly reduced the
      antiatherogenic effect of estrogen (P < 0.01). There was no significant
      difference between the placebo group given -NAME and the group treated with
      placebo alone. At the previously endothelium-denuded site, estrogen had no effect
      on atherosclerosis development, whereas -NAME combined with estrogen
      significantly increased atherogenesis (P < 0.05). The effects of levormeloxifene
      were almost similar to those of estrogen. Active vascular concentrations of -NAME
      were demonstrated in an additional study, in which maximal aortic/coronary
      endothelium-dependent relaxation was significantly inhibited in rabbits given 
      NAME. Thus, in this study a considerable part of the plasma lipid-independent
      antiatherogenic effect of estrogen was mediated through its effect on endothelial
      NO in cholesterol-fed rabbits. The results for levormeloxifene suggest a common
      mechanism of action for estrogen and partial estrogen receptor agonists on
      atherogenesis.

PMID- 9259583
TI  - Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin
      collagen is not accelerated in diabetes. Evidence against a generalized increase
      in oxidative stress in diabetes.
AB  - The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine
      increase in skin collagen with age and at an accelerated rate in diabetes. Their
      age-adjusted concentrations in skin collagen are correlated with the severity of
      diabetic complications. To determine the relative roles of increased glycation
      and/or oxidation in the accelerated formation of glycoxidation products in
      diabetes, we measured levels of amino acid oxidation products, distinct from
      glycoxidative modifications of amino acids, as independent indicators of
      oxidative stress and damage to collagen in aging and diabetes. We show that ortho
      tyrosine and methionine sulfoxide are formed in concert with Nepsilon
      (carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro,
      and that they also increase with age in human skin collagen. The age-adjusted
      levels of these oxidized amino acids in collagen was the same in diabetic and
      nondiabetic subjects, arguing that diabetes per se does not cause an increase in
      oxidative stress or damage to extracellular matrix proteins. These results
      provide evidence for an age-dependent increase in oxidative damage to collagen
      and support previous conclusions that the increase in glycoxidation products in
      skin collagen in diabetes can be explained by the increase in glycemia alone,
      without invoking a generalized, diabetes-dependent increase in oxidative stress.

PMID- 9259584
TI  - Depletion of reactive advanced glycation endproducts from diabetic uremic sera
      using a lysozyme-linked matrix.
AB  - Diabetic uremic sera contain excessive amounts of reactive advanced glycation
      endproducts (AGEs), which accelerate the vasculopathy of diabetes and end-stage
      renal disease. To capture in vivo-derived toxic AGEs, high affinity AGE-binding
      protein lysozyme (LZ) was linked to a Sepharose 4B matrix. Initial studies showed
      that > 80% of 125I-AGE-BSA was retained by the LZ matrix, compared with < 10%
      retained by a control matrix. More than 60% of AGE-lysine was captured by the LZ
      matrix, and the LZ-bound fraction retained immunoreactivity and cross-linking
      activity, but had little intrinsic fluorescence (370/440 nm). After passage
      through the LZ matrix, AGE levels in diabetic sera (0.37+/-0.04 U/mg) were
      significantly reduced to a level (0.09+/-0.01 U/mg; n = 10; P < 0. 0001)
      comparable with the level of normal human serum, whereas total protein absorption
      was < 3%. The AGE-enriched serum fraction exhibited cross-linking activity, which
      was completely prevented by aminoguanidine. Among numerous LZ-bound proteins in
      diabetic uremic sera, three major proteins "susceptible" to AGE modification were
      identified: the immunoglobulin G light chain, apolipoprotein J (clusterin/SP
      40,40), and the complement 3b beta chain. These findings indicate that the LZ
      linked AGE affinity column may serve as an efficient method for the depletion of
      toxic AGEs from sera, including specific AGE-modified proteins that may be linked
      to altered immunity, lipoprotein metabolism, and accelerated vasculopathy in
      renal failure patients with or without diabetes.

PMID- 9259585
TI  - Characterization of T cell repertoire in patients with graft-versus-leukemia
      after donor lymphocyte infusion.
AB  - The clinical efficacy of donor lymphocyte infusions (DLI) in patients with
      relapsed chronic myelocytic leukemia after allogeneic bone marrow transplantation
      has been demonstrated in several recent studies. Although it is presumed that
      allogeneic T cells mediate this graft-versus-leukemia (GVL) effect, the influence
      of DLI on the T cell compartment of recipients has not been determined. To
      characterize the immunologic effects of DLI and to identify T cell changes
      selectively associated with the GVL response, we analyzed the T cell receptor
      (TCR) repertoire in four patients with relapsed chronic myelocytic leukemia who
      achieved a complete remission after infusion of CD4+ lymphocytes from HLA
      identical sibling donors. Only one of the four patients developed clinically
      significant graft-versus-host disease (GVHD) after infusion of donor lymphocytes.
      TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies
      in serial samples obtained over a 1-yr period before and after DLI. Results were
      compared to 10 normal donors. Before DLI, all four patients were found to have
      abnormal TCR Vbeta repertoire in peripheral T cells, associated with a large
      number of clonal and oligoclonal patterns. Abnormal TCR patterns persisted for at
      least 3 mo after DLI, but thereafter gradually began to normalize. By 1 yr after
      DLI, all patients demonstrated almost complete normalization of Vbeta repertoire
      with polyclonal representation within almost all Vbeta gene subfamilies. We also
      examined changes in the TCR Vbeta repertoire associated with the disappearance of
      Ph+ cells. In each patient, we were able to identify the expansion of at least 1
      Vbeta gene subfamily that coincided with the time of the cytogenetic response. In
      one patient who was studied in greater detail, CDR3 size analysis of serial
      samples after DLI indicated that these changes were associated with the
      appearance of clonal T cells. This finding was confirmed through CDR3 sequence
      analysis and use of CDR3 clone-specific oligonucleotide probes. A putative GVL
      clone identified by this technique was not detectable in either donor or patient
      T cells before DLI, but persisted in peripheral T cells for approximately 1 yr.
      These experiments therefore provide evidence for the clonal expansion of
      allogeneic T cells that may be selective mediators of antileukemia activity
      without also mediating graft-versus-host disease.

PMID- 9259586
TI  - Subendothelial retention of lipoprotein (a). Evidence that reduced heparan
      sulfate promotes lipoprotein binding to subendothelial matrix.
AB  - Vessel wall subendothelial extracellular matrix, a dense mesh formed of
      collagens, fibronectin, laminin, and proteoglycans, has important roles in lipid
      and lipoprotein retention and cell adhesion. In atherosclerosis, vessel wall
      heparan sulfate proteoglycans (HSPG) are decreased and we therefore tested
      whether selective loss of HSPG affects lipoprotein retention. A matrix
      synthesized by aortic endothelial cells and a commercially available matrix
      (Matrigel; , Rutherford, NJ) were used. Treatment of matrix with
      heparinase/heparitinase (1 U/ml each) increased LDL binding by approximately 1.5
      fold. Binding of lipoprotein (a) [Lp(a)] to both subendothelial matrix and
      Matrigel(R) increased 2-10-fold when the HSPG were removed by heparinase
      treatment. Incubation of endothelial cells with oxidized LDL (OxLDL) or
      lysolecithin resulted in decreased matrix proteoglycans and increased Lp(a)
      retention by matrix. The effect of OxLDL or lysolecithin on endothelial PG was
      abolished in the presence of HDL. The decrease in matrix HSPG was associated with
      production of a heparanase-like activity by OxLDL-stimulated endothelial cells.
      To test whether removal of HSPG exposes fibronectin, a candidate Lp(a) binding
      protein in the matrix, antifibronectin antibodies were used. The increased Lp(a)
      binding after HSPG removal was inhibited 60% by antifibronectin antibodies.
      Similarly, the increased Lp(a) binding to matrix from OxLDL-treated endothelial
      cells was inhibited by antifibronectin antibodies. We hypothesize that
      atherogenic lipoproteins stimulate endothelial cell production of heparanase.
      This enzyme reduces HSPG which in turn promotes Lp(a) retention.

PMID- 9259588
TI  - Replacing the first epidermal growth factor-like domain of factor IX with that of
      factor VII enhances activity in vitro and in canine hemophilia B.
AB  - Using the techniques of molecular biology, we made a chimeric Factor IX by
      replacing the first epidermal growth factor-like domain with that of Factor VII.
      The resulting recombinant chimeric molecule, Factor IXVIIEGF1, had at least a
      twofold increase in functional activity in the one-stage clotting assay when
      compared to recombinant wild-type Factor IX. The increased activity was not due
      to contamination with activated Factor IX, nor was it due to an increased rate of
      activation by Factor VIIa-tissue factor or by Factor XIa. Rather, the increased
      activity was due to a higher affinity of Factor IXVIIEGF1 for Factor VIIIa with a
      Kd for Factor VIIIa about one order of magnitude lower than that of recombinant
      wild-type Factor IXa. In addition, results from animal studies show that this
      chimeric Factor IX, when infused into a dog with hemophilia B, exhibits a greater
      than threefold increase in clotting activity, and has a biological half-life
      equivalent to recombinant wild-type Factor IX.

PMID- 9259587
TI  - The mitogen-activated protein kinase pathway can mediate growth inhibition and
      proliferation in smooth muscle cells. Dependence on the availability of
      downstream targets.
AB  - Activation of the classical mitogen-activated protein kinase (MAPK) pathway leads
      to proliferation of many cell types. Accordingly, an inhibitor of MAPK kinase, PD
      098059, inhibits PDGF-induced proliferation of human arterial smooth muscle cells
      (SMCs) that do not secrete growth-inhibitory PGs such as PGE2. In striking
      contrast, in SMCs that express the inducible form of cyclooxygenase (COX-2),
      activation of MAPK serves as a negative regulator of proliferation. In these
      cells, PDGF-induced MAPK activation leads to cytosolic phospholipase A2
      activation, PGE2 release, and subsequent activation of the cAMP-dependent protein
      kinase (PKA), which acts as a strong inhibitor of SMC proliferation. Inhibition
      of either MAPK kinase signaling or of COX-2 in these cells releases them from the
      influence of the growth-inhibitory PGs and results in the subsequent cell cycle
      traverse and proliferation. Thus, the MAPK pathway mediates either proliferation
      or growth inhibition in human arterial SMCs depending on the availability of
      specific downstream enzyme targets.

PMID- 9259589
TI  - Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1
      infection.
AB  - A large number of evidences indicate that progression of HIV disease is driven by
      an increase in viral burden. It is still unclear, however, to what extent this is
      contributed by the dysregulation of the molecular mechanisms governing virus gene
      expression at the transcriptional or posttranscriptional levels. To address this
      issue, several quantitative virologic parameters (including provirus
      transcriptional activity and splicing pattern) were analyzed in individuals with
      nonprogressive HIV infection and compared with those of a matched group of
      progressor patients. Exact quantification was achieved by a competitive PCR
      procedure using a multicompetitor template. Nonprogressors were characterized by
      striking differences in the levels of viremia, provirus copy number, and overall
      levels of all viral mRNA classes in peripheral blood mononuclear cells.
      Additionally, the transcriptional activity of the proviral DNA in these patients
      was mainly engaged in the production of multiprocessed transcripts, with a
      pattern resembling the early phases of the experimental infection. Taken
      together, these results show that both viral load and provirus transcription
      pattern are remarkably different in infected individuals nonprogressing toward
      overt disease, and further support the notion that disease progression is
      accompanied by a change in the kinetics of HIV gene expression.

PMID- 9259590
TI  - Perforin/granzyme-dependent and independent mechanisms are both important for the
      development of graft-versus-host disease after murine bone marrow
      transplantation.
AB  - Graft-versus-host disease (GvHD) is the major limiting toxicity of allogeneic
      bone marrow transplantation. T cells are important mediators of GvHD, but the
      molecular mechanisms that they use to induce GvHD are controversial. Three
      effector pathways have been described for cytotoxic T lymphocytes: one requires
      perforin and granzymes, the second Fas (APO-1; CD95) and its ligand. Thirdly,
      secreted molecules (e.g., TNF-alpha, gamma-IFN) can also mediate cytotoxicity.
      Together, these mechanisms appear to account for virtually all cytotoxicity
      induced by activated CTL in standard in vitro lytic assays. Using transplants
      across histocompatibility barriers, we were able to analyze the contributions of
      these effector molecules to cell-mediated cytotoxicity in vivo in a GvHD model.
      We found that Fas ligand is an important independent mediator of class II
      restricted acute murine GvHD, while perforin/granzyme-dependent mechanisms have
      only a minor role in that compartment. In contrast, perforin/ granzyme-dependent
      mechanisms are required for class I-restricted acute murine GvHD, while Fas
      ligand is not. The perforin/granzyme pathway may therefore represent a novel
      target for anti-GvHD drug design. In support of this approach, we provide
      additional data suggesting that specific perforin/granzyme inhibitors should not
      adversely affect hematopoietic recovery after transplantation.

PMID- 9259591
TI  - Soluble factor(s) produced by adult bone marrow stroma inhibit in vitro
      proliferation and differentiation of fetal liver BFU-E by inducing apoptosis.
AB  - Hematopoiesis occurs in different organs during fetal development. Several
      studies suggest that the growth of hematopoietic progenitors at one stage of
      ontogenic maturation may not be supported by a microenvironment from a different
      ontogenic stage. To determine if human fetal liver (FL) clonogenic progenitors
      can develop in an adult bone marrow (ABM) microenvironment, we compared growth of
      BFU-E and CFU-GM from 7-14-wk-old FL, 11-20-wk-old fetal bone marrow (FBM),
      umbilical cord blood (UCB), or ABM in clonogenic medium with or without ABM
      stroma. In contrast to BFU-E from FBM, UCB, or ABM, soluble factor(s) produced by
      ABM stroma severely suppressed growth of 98% of FL BFU-E by inducing apoptosis of
      cells beyond early erythroblast stage. The nature of the soluble factor remains
      unknown, although we have evidence that it is heat labile with molecular mass <
      10 kD. Antibody neutralization studies indicate that TGF-beta1, IL-1, TNF-alpha,
      macrophage inflammatory protein (MIP)-1alpha, or IFN-gamma are not responsible.
      The observation that FL progenitors may not be capable of differentiating when
      transferred to an ABM microenvironment may have important implications for FL
      transplantation into postnatal recipients. Further, this demonstrates that
      ontogenic stage-specific interactions between hematopoietic progenitors and their
      microenvironment are important for the normal development of hematopoiesis.

PMID- 9259592
TI  - Do beta-chemokines have clinical relevance in HIV infection?
AB  - The role of beta-chemokines in HIV infection was evaluated. The kinetics of
      regulated upon activation of normal T cell expressed and secreted, macrophage
      inflammatory protein-1alpha, and macrophage inflammatory protein 1beta production
      by stimulated T lymphocytes did not differ substantially between HIV-infected
      (asymptomatic and with AIDS) and uninfected subjects. Maximal production of these
      beta-chemokines by activated peripheral blood cells was higher in the infected
      individuals than in uninfected individuals, but no significant difference was
      observed between healthy infected subjects and AIDS patients. Evaluation of the
      effect of HIV replication on beta-chemokine production indicated that acute
      infection of CD4+ T cells with non-syncytia-inducing (NSI) viruses generally
      increased beta-chemokine production two to eightfold, whereas with SI strains, it
      led to decreased production. The sensitivity of an individual's virus to beta
      chemokine-mediated inhibition correlated with the NSI virus phenotype and a
      healthy clinical state. 50% of the AIDS patients, however, had NSI viruses that
      were sensitive to beta-chemokines. Finally, anti-beta-chemokine-neutralizing
      antibodies caused a more rapid release of HIV by CD4+ T cells naturally infected
      by NSI, but not SI, viruses indicating that endogenously produced chemokines can
      affect HIV production in culture. These findings suggest that beta-chemokines may
      affect HIV replication when an NSI virus is involved, but provide little evidence
      that they substantially influence HIV infection and pathogenesis.

PMID- 9259595
TI  - Doctors' fees.

PMID- 9259593
TI  - Regulation of glucose homeostasis in humans with denervated livers.
AB  - The liver plays a major role in regulating glucose metabolism, and since its
      function is influenced by sympathetic/ parasympathetic innervation, we used liver
      graft as a model of denervation to study the role of CNS in modulating hepatic
      glucose metabolism in humans. 22 liver transplant subjects were randomly studied
      by means of the hyperglycemic/ hyperinsulinemic (study 1),
      hyperglycemic/isoinsulinemic (study 2), euglycemic/hyperinsulinemic (study 3) as
      well as insulin-induced hypoglycemic (study 4) clamp, combined with bolus
      continuous infusion of [3-3H]glucose and indirect calorimetry to determine the
      effect of different glycemic/insulinemic levels on endogenous glucose production
      and on peripheral glucose uptake. In addition, postabsorptive glucose homeostasis
      was cross-sectionally related to the transplant age (range = 40 d-35 mo) in 4
      subgroups of patients 2, 6, 15, and 28 mo after transplantation. 22 subjects with
      chronic uveitis (CU) undergoing a similar immunosuppressive therapy and 35 normal
      healthy subjects served as controls. The results showed that successful
      transplantation was associated with fasting glucose concentration and endogenous
      glucose production in the lower physiological range within a few weeks after
      transplantation, and this pattern was maintained throughout the 28-mo follow-up
      period. Fasting glucose (4. 55+/-0.06 vs. 4.75+/-0.06 mM; P = 0.038) and
      endogenous glucose production (11.3+/-0.4 vs. 12.9+/-0.5 micromol/[kg.min]; P =
      0.029) were lower when compared to CU and normal patients. At different
      combinations of glycemic/insulinemic levels, liver transplant (LTx) patients
      showed a comparable inhibition of endogenous glucose production. In contrast, in
      hypoglycemia, after a temporary fall endogenous glucose production rose to values
      comparable to those of the basal condition in CU and normal subjects (83+/-5 and
      92+/-5% of basal), but it did not in LTx subjects (66+/-7%; P < 0.05 vs. CU and
      normal subjects). Fasting insulin and C-peptide levels were increased up to 6 mo
      after transplantation, indicating insulin resistance partially induced by
      prednisone. In addition, greater C-peptide but similar insulin levels during the
      hyperglycemic clamp (study 1) suggested an increased hepatic insulin clearance in
      LTx as compared to normal subjects. Fasting glucagon concentration was higher 6
      mo after transplantation and thereafter. During euglycemia/hyperinsulinemia
      (study 3), the insulin-induced glucagon suppression detectable in CU and normal
      subjects was lacking in LTx subjects; furthermore, the counterregulatory response
      during hypoglycemia was blunted. In summary, liver transplant subjects have
      normal postabsorptive glucose metabolism, and glucose and insulin challenge
      elicit normal response at both hepatic and peripheral sites. Nevertheless, (a)
      minimal alteration of endogenous glucose production, (b) increased concentration
      of insulin and glucagon, and (c) defective counterregulation during hypoglycemia
      may reflect an alteration of the liver-CNS-islet circuit which is due to
      denervation of the transplanted graft.

PMID- 9259596
TI  - Rising costs and the new GP--quo vadis?

PMID- 9259594
TI  - Nitric oxide decreases stability of mRNAs encoding soluble guanylate cyclase
      subunits in rat pulmonary artery smooth muscle cells.
AB  - Nitric oxide stimulates soluble guanylate cyclase (sGC) to convert GTP to the
      intracellular second messenger cGMP. In rat pulmonary artery smooth muscle cells,
      sGC is an obligate heterodimer composed of alpha1 and beta1 subunits. We
      investigated the effect of NO donor compounds on sGC subunit gene expression in
      rat pulmonary artery smooth muscle cells. Sodium nitroprusside and S-nitroso
      glutathione decreased sGC subunit mRNA and protein levels, as well as sGC enzyme
      activity. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an sGC inhibitor, blocked
      the effect of sodium nitroprusside on sGC subunit gene expression, whereas 8
      bromo cGMP decreased subunit mRNA levels, demonstrating that NO-mediated decrease
      in sGC subunit mRNA levels is cGMP-dependent. sGC subunit mRNA levels decreased
      more rapidly in rat pulmonary artery smooth muscle cells exposed to NO than in
      cells exposed to actinomycin D, suggesting that NO decreases sGC subunit mRNA
      stability. Actinomycin D and cycloheximide blocked the ability of NO to decrease
      sGC subunit mRNA levels. These results demonstrate that NO decreases sGC subunit
      mRNA stability via a transcription- and translation-dependent mechanism.

PMID- 9259597
TI  - Complications in the recovery room.

PMID- 9259598
TI  - 1996 survey of housing estate practice costs and GP fees in Singapore.

PMID- 9259599
TI  - Anaesthetic complications in the recovery room.
AB  - INTRODUCTION: The immediate post-operative period in the recovery room is a known
      period of high risk for anaesthetic complications to occur. AIMS: We wanted to
      know the incidence and nature of our recovery room patients in the main-theatre
      complex of Hospital Kuala Lumpur. METHOD: A prospective study was conducted over
      a two-month period on all patients receiving either regional and/or general
      anaesthesia by an anaesthetic doctor admitted to this recovery room.
      Complications were documented according to predefined criteria. RESULTS: Out of a
      total of 1,995 patients, 50(2.5%) had some form of anaesthetic complication.
      Fifteen patients had more than one complication. The most common was pain (23
      patients) followed closely by nausea and vomiting (21 patients). There were 32
      patients with CNS problems (including the 23 with pain), 21 with GIT, 10 with
      CVS, 2 with respiratory and 3 with other problems. CONCLUSION: Our recovery room
      complication rate is acceptably low. Knowing the type and frequency of problems
      (in this case, mainly pain and nausea and vomiting) can further improve the
      figure. The role of anaesthesiologists has expanded as they are not only expected
      to ascertain the safety but also the comfort of patients post-operatively.

PMID- 9259600
TI  - A 3-year review of meconium aspiration syndrome.
AB  - AIM OF STUDY: To review the incidence, morbidity and mortality of Meconium
      Aspiration Syndrome (MAS). To identify possible predictors of MAS in newborns
      with thick meconium-stained amniotic fluid (MSAF) at delivery. METHODOLOGY: Case
      records of babies with MSAF delivered in Singapore General Hospital from 1.1.1991
      to 31.12.1993 were studied retrospectively. RESULTS: In the study period, 1,893
      babies (15% of live births) had MSAF and 174 babies (1.4% live births) developed
      MAS. The incidences of MAS in newborns with light, moderate and thick MSAF were
      0.3%, 5.8% and 61% respectively. Complications associated with MAS were metabolic
      acidosis (52%), air leak syndrome (2%), persistent pulmonary hypertension (2%)
      and hypoxic ischaemic encephalopathy (0.5%). The mortality rate of babies with
      MAS was 2%. Newborns with thick MSAF were more likely to develop MAS if they were
      males, small-for- gestational-age, had fetal distress and meconium was sucked
      from the trachea at birth. CONCLUSION: Vigilant perinatal monitoring of high risk
      babies with MSAF and proper resuscitation at birth would help reduce the
      incidence of MAS and its associated complications.

PMID- 9259602
TI  - Alcoholism--treating the disease.

PMID- 9259601
TI  - A two-year experience of an acute pain service in Singapore.
AB  - The first anaesthesia-based acute pain service in Singapore is described. The
      benefits, risks and resource implications of such a service during its first two
      years are reviewed. One thousand two hundred and sixty-eight (1,268) post
      operative patients were treated with either patient-controlled analgesia (310
      patients) or epidural opioid analgesia (958 patients). Retrospective analysis of
      the data revealed good patient satisfaction with a low incidence of potentially
      life threatening side-effects: more than 79% of patients reported satisfaction
      with pain control while only 0.2% of patients receiving epidural opioid analgesia
      experienced clinically significant respiratory depression. There were no reports
      of respiratory depression in the patient-controlled analgesia group. The authors
      conclude that the provision of an acute pain service in the local context was
      safe and resulted in excellent post-operative patient satisfaction.

PMID- 9259604
TI  - Bilateral lower limb oedema due to a distended urinary bladder.
AB  - A 91-year-old Chinese man developed bilateral lower limb oedema due to venous
      obstruction resulting from a distended urinary bladder. After the bladder was
      decompressed by urethral catheterisation, the bilateral lower limb oedema
      promptly subsided. Although a distended urinary bladder is a rare cause of
      bilateral lower limb oedema, it can be easily recognised by palpation of the
      lower abdomen and the relief of symptoms by urethral catheterisation is most
      rewarding.

PMID- 9259603
TI  - Cloverleaf skull--when should one operate?
AB  - Cloverleaf skull or kleeblattschadel usually occurs as a result of premature
      closure of the cranial sutures, with accompanying hydrocephalus, proptosis,
      cranial base and midface hypoplasia. The incidence of this abnormality is rare,
      with less than 130 reported cases in the literature, and is associated with
      various congenital syndromes. Conventional surgical management advocates shunting
      prior to definitive craniotomy and bone remodeling. We report an unusual case of
      Pfeiffer syndrome with associated cloverleaf skull deformity, in which early
      surgery was vital for decompression of raised intracranial pressure and shunt
      independence for the first six months. A secondary craniofacial procedure was
      performed at nine months of age to improve cosmesis. In such cases, good outcome
      can be achieved if aggressive surgery is combined with good paediatric
      anaesthesia and intensive care.

PMID- 9259605
TI  - An unusual case of sorethroat: nasopharyngeal melioidosis.
AB  - A 14-year-old Chinese female presented with severe sorethroat and swinging fever
      for two weeks despite one course of oral amoxycillin followed by one course of
      Unasyn (combination of sultamicillin, sulbactam and ampicillin). Throat swab grew
      Pseudomonas pseudomallel. Serology for its antibodies was very strongly positive
      (> 1:512). In this part of the world the IHA titre of 1:16 or greater is
      significant. She was successfully treated with intravenous ceftazidime. The
      swinging fever settled within two days. The nasopharyngeal and oropharyngeal
      lesions cleared after a week of therapy. A further two weeks of Ceftazidime were
      given to ensure a complete resolution of the infection. Oral tetracycline was
      given for maintenance therapy. Melioidosis involving various organs have been
      reported particularly pulmonary melioidosis. Nasopharyngeal melioidosis has not
      been reported, as far as we know. This is the first reported case.

PMID- 9259606
TI  - Clinics in diagnostic imaging (25). Aggressive vertebral haemangioma.
AB  - A 30-year-old female presented with a three month history of back pain.
      Radiographs and computed tomography indicated an aggressive haemangioma of T12
      which was confirmed on red cell scintigraphy. The varying imaging appearances of
      non-aggressive and aggressive vertebral haemangiomas are described, emphasizing
      the ability of aggressive haemangiomas to mimic metastases on magnetic resonance
      imaging. The therapeutic role of embolisation as an adjunct ro surgery is
      stressed.

PMID- 9259607
TI  - Electrocardiographic case: a non-ischaemic cause of ST-segment elevation.

PMID- 9259608
TI  - Investigations of pneumocystosis among humans and rodents in Lithuania.
AB  - Pneumocystosis (Pneumocystis carinii pneumonia) is a parasitic disease which in
      Lithuania used to be diagnosed only with the use of pathohistological methods.
      The aim of our study was to determine prevalence of P. carinii antibodies among
      children and women, using immunochemical method (ELISA) and to find out which
      groups of patients have higher antibody titres. We also addressed the question of
      infection with P. carinii among rodents. After investigating 9 species of rodents
      it was found that mostly infected is brown rat (Rattus norvegicus)--42.9% of them
      were found infected. The least infected was bank vole (Clethrionomys glareolus)-
      5.9%. The brown rat lives on hatch of domestic birds, rabbits or drinks eggs,
      while rodents in nature live on insects, molluscs, amphibians etc. European water
      voles (Arvicola terrestris) and field voles (Microtus arvalis) are vegetable
      feeders. Our data shows that those species of rodents were not infected with
      pneumocysts.

PMID- 9259609
TI  - Tapeworms morphological changeability in the chain of Hymenolepis diminuta WMS
      "strain" generations.
AB  - The investigations covered 54 subsequent generations of Hymenolepis diminuta WMS
      "strain" obtained through the administration of 6 cysticercoids of tapeworm to
      Wistar strain rats and WAG alb. rats. The number of tapeworms at 2.5 months after
      the infection of rats ranged from 3 to 6, on the average 5.2. Taking into
      consideration the most important type 1p2a (one testis on the poral side and two
      testes on the aporal side), 0p3a, 1p3a and 2p1a proglottids a significant
      differences was found in the distribution of the numerousity of type 1p3a
      proglottids (P < 0.05). This indicates a possibility of an unguided change of the
      number of proglottids of this type in a period covering 54 subsequent H. diminuta
      generations bred in laboratory conditions.

PMID- 9259610
TI  - Survival of larvae of Nippostrongylus brasiliensis (nematoda) in solutions of
      toxic substances.
AB  - The aim of this study was to determine the action of zinc, copper, lead and
      cadmium compounds upon N. brasiliensis invasive nematode larvae. The tested
      larvae were kept in ZnCl2, CuCl2, Pb(NO3)2 and CdCl2 solutions. The
      concentrations of toxic substances applied for the study corresponded with level
      of environmental pollution. All toxins reduced life-space of larvae. In control
      group they survived about 69 days. In solutions of the Zn, contaminated with 10,
      50, 100 and 200 ppm of toxic substance, they survived 42, 16, 14 days and 72
      hours. In solution of Cu, contaminated with 5, 10, 50 and 200 ppm of toxin, life-
      space was reduced to 51, 21, 7 days and 54 hours, respectively. Lead reduced live
      -space of larvae to 26 days already at the low concentration of 10 ppm and in all
      higher concentrations (20, 50 and 200 ppm) their survival changed insignificantly
      (to 22 days). In solution of Cd, contaminated with 0.1 and 0.3 ppm larvae died
      after 39 and 17 days, respectively, while at higher concentrations of this toxin
      (3 and 10 ppm) larvae survived only 54 and 30 hours, respectively.

PMID- 9259611
TI  - The distribution of nitric oxide synthase in human corpus cavernosum on various
      impotent patients.
AB  - Recent evidence implicates NO (Nitric oxide) as the principal mediator in an
      erection. To investigate the role of NO in the human erectile function, we
      studied the distribution pattern of nitroxergic fibers in the corpus cavernosum
      specimens obtained from 38 men using nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) histochemistry. Diffusely scattered delicate nerve fibers
      showing blue color reaction after NADPH-d histochemical staining were observed in
      normal control specimens from potent men. The neurogenic impotence group showed a
      statistically-significant decrease in the number of positive fibers compared to
      the normal control group. The number of positive fibers in the non-neurogenic
      impotence group was decreased compared to the normal control group but was
      statistically insignificant. With nitric oxide synthase (NOS) immunohistochemical
      stain, immunoreactive nerve bundles were easily seen in normal control specimens
      from potent men. NOS immunoreactive nerve bundles were contained within the
      corpus cavernosa which stained with NADPH-d reaction. Our results suggest that
      nitric oxide, a potent smooth muscle relaxing neurotransmitter in the autonomic
      nervous system, plays a physiologic role in erectile function and NADPH-d enzyme
      histochemical staining on the biopsied corpus cavernosum may be used as an
      important diagnostic method in the evaluation of neurogenic impotence.

PMID- 9259612
TI  - Heparin attenuated neutrophil infiltration but did not affect renal injury
      induced by ischemia reperfusion.
AB  - Although heparin is better known as an anticoagulant, it also has several anti
      inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis
      and oxygen free radical production. In addition, heparin is also known to act as
      an oxygen radical scavenger. Our hypothesis was that heparin would attenuate
      renal ischemia reperfusion injury. In this study, we investigated whether heparin
      had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were
      prepared for the chronic study with venous, arterial and urinary catheters
      inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed
      on renal arteries. After a 5-day recovery period, the sheep were randomized to
      either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal
      artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9%
      NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent
      volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal
      ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum
      creatinine (Scr), and creatinine clearance (CrCl) were determined at various
      intervals during both the ischemic and reperfusion periods. Kidney tissue samples
      were obtained at autopsy for histologic examination. As a result, there were
      significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/-
      0.79, P < 0.05) between the control and heparin treatment groups, but not in the
      degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin
      significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within
      the interstitium, but it did not affect the degree of renal damage as measured by
      urinary chemistries or renal tubular damage as assessed by histopathologic
      evaluation.

PMID- 9259613
TI  - Renal ischemia-reperfusion injury does not induce pulmonary dysfunction in sheep.
AB  - It has already been shown that pulmonary injury is induced after intestinal or
      hind limb ischemia-reperfusion injury. The purpose of this study was to determine
      the effect of renal ischemia-reperfusion injury on the pulmonary system. We
      compared the pulmonary effects of 60 and 90 minutes ischemia followed by 24 hour
      reperfusion in sheep kidneys. Standard hemodynamic measurements, arterial and
      mixed venous blood gas analysis, urine output, creatinine clearance, and blood
      urea nitrogen concentration were measured at baseline, during ischemia and
      reperfusion periods. After 24 hours of reperfusion, animals were sacrificed and
      underwent autopsy with collection of samples for wet/dry lung-weight ratio, lung
      tissue conjugated dienes, and renal histology. As expected, renal ischemia
      resulted in an increased serum creatinine and blood urea nitrogen concentrations,
      decreased creatinine clearance, and histological evidence of renal damage. There
      was no evidence of pulmonary hypertension or hypoxemia during renal ischemia
      reperfusion. There was also no significant difference in the wet/dry lung-weight
      ratios or lung tissue conjugated denies between the two ischemic groups (60 and
      90 minutes) and nonischemic control group. These results suggest that renal
      ischemia-reperfusion injury was not associated with a significant degree of
      pulmonary dysfunction.

PMID- 9259614
TI  - Anterior clinoid process and optic strut in Koreans.
AB  - The anterior clinoid process and the optic strut are often removed during
      operation on the anterior part of the cavernous sinus. Therefore it is important
      for neurosurgeons to verify their dimensions and variations. The purpose of this
      study was to investigate the dimension and the variation of the anterior clinoid
      process and to describe the locational variation of the optic strut. Seventy
      three skulls of Korean adults were used. The average length, basal width and
      thickness of the anterior clinoid process were 9.18 +/- 1.55, 9.63 +/- 1.49 and
      5.32 +/- 1.07 mm, respectively. The average thickness of the optic strut was 2.9
      +/- 1.15 mm and it was commonly attached to anterior two-fifths of the anterior
      clinoid process. The complete caroticoclinoid canal was observed in 4.1%, however
      it was incomplete in 11.6%. The incidence of a caroticoclinoid canal in Koreans
      was relatively low compared with other races.

PMID- 9259615
TI  - Telomerase activity: a potential marker of bladder transitional cell carcinoma in
      bladder washes.
AB  - The enzyme telomerase maintains a constant telomere length in immortalized cells,
      allowing unlimited cell proliferation. Almost all cancer cells express telomerase
      activity. However, little data is available regarding the role of telomerase
      activity in the detection of bladder cancer with a bladder wash specimen. We
      detected telomerase activity in a bladder wash specimen of bladder cancer and
      normal tissues, and compared them with final pathologic diagnosis. Twenty-three
      patients with transitional cell carcinoma (TCC) of the bladder were enrolled in
      our study. A bladder wash specimen was obtained before transurethral resection of
      the bladder (TURB) and normal and cancer tissues from the same patients during
      TURB. Telomerase activity was analyzed in each specimen a using telomeric repeat
      amplification protocol (TRAP) assay based on polymerase chain reaction (PCR)
      technique. Cytologic diagnosis was performed using Papanicolaou's stain with
      cytocentrifuged cytology preparation. We observed telomerase activity in 95.7%
      (22/23) of bath cancer tissues and bladder wash specimens; only one case did not
      express telomerase activity. Telomerase activity was undetected in all normal
      tissues except one, which was obtained from a patient with carcinoma in situ. A
      total of 69.6% (16/23) of wash specimens were positive in cytopathologic
      diagnosis. The accuracy of cytopathologic diagnosis in pathologic grade 2 or 3
      was relatively high (83.3%, 15/18). However, in five cases of grade 1 TCC only
      20% (1/5) of cytologic diagnosis was positive whereas the telomerase activity of
      wash specimens was detected in 80% (4/5). Our data demonstrates that not only the
      majority of human bladder cancer tissues, but also the bladder wash specimens
      obtained from patients with TCC, expressed telomerase activity. It indicates that
      telomerase activity may be a reliable marker in detecting bladder cancer
      especially in cases with a low grade that bladder wash cytology can miss.

PMID- 9259616
TI  - The effect of anti-hypertensive drugs on DNA synthesis and proliferation of
      cultured rat aortic smooth muscle cells.
AB  - The aim of this study was to elucidate the effects of anti-hypertensive drugs,
      nifedipine, furosemide, hydrochlorothiazide, captopril, and atenolol on DNA
      synthesis and proliferation of cultured rat aortic smooth muscle cells induced by
      fetal calf serum. Aortic smooth muscle cells from Sprague-Dawley rats were
      isolated, cultured, and seeded in multi-well plates. When confluent, cells were
      cultured in a conditioned medium without fetal calf serum. After 72 hours, cells
      were cultured in the medium retaining 10% fetal calf serum with or without anti
      hypertensive drugs by increasing the concentration between 10(-8) and 10(-4) M.
      DNA synthesis was assessed by [3H]-thymidine uptake and proliferation by cell
      numbers using a hemocytometer. Nifedipine at a concentration of 10(-5) M and 5 x
      10(-5) M inhibited serum-induced DNA synthesis significantly by 50.8% and 86.6%,
      respectively (p < 0.05). The results of cell numbers paralleled those of 3H
      thymidine incorporation. Serum-induced DNA synthesis was also reduced by 32.6% at
      the highest dose of furosemide (10(-4) M), but there was no statistical
      significance. Hydrochlorothiazide, captopril, and atenolol did not show anti
      proliferative effect throughout any of the doses. In conclusion, among the
      various anti-hypertensive drugs, nifedipine seems to be most beneficial in view
      of its direct inhibitory effect on DNA synthesis and proliferation of smooth
      muscle cells, as well as for its anti-hypertensive effect.

PMID- 9259617
TI  - The effect of aflatoxin B1 on the expression of early response genes and
      transforming growth factor-alpha in CCl4 induced rat liver injury.
AB  - Aflatoxin B1 (AFB1), a fungal toxin produced by Aspergillus flavus, is known to
      be a possible hepatocarcinogen. But the molecular biologic changes which may
      occur following exposure to AFB1 are not known and thus the carcinogenesis is not
      yet understood. This study was performed to examine the expressions of c-myc, c
      fos and TGF-alpha genes and to investigate the possible role of those molecular
      biologic changes in hepatic regeneration and in the development of hepatocellular
      carcinoma (HCC). Sprague-Dawley rats were divided into 3 groups: Carbon
      tetrachloride (CCl4) only was administered to group I, AFB1 only was administered
      to group II and a combination of AFB1 and CCl4 was administered to group III. The
      animals were sacrificed at 0.5, 1, 2, 6, 12, 24, 48, and 72 hours after
      treatment. In addition to the examination of the hematoxylin-eosin stained
      sections, hepatic regeneration and apoptosis were analyzed quantitatively by
      bromodeoxyuridine (BrdU)-anti-BrdU immunohistochemistry and TUNEL assay utilizing
      apoptosis kit, respectively. The hepatic expressions of c-myc, c-fos and
      transforming growth factor-alpha (TGF-alpha) were examined by
      immunohistochemistry and studied by Western blot. The number of BrdU labelled
      cells and the degree of necrosis/apoptosis were comparable among the different
      groups. Livers of the group II rats showed nearly normal histology without
      regeneration and necrosis/apoptosis. In groups I and III, the number of BrdU-
      labelled cells showed an increase at 48 hours after treatment, and the increment
      was significantly higher in group I than in group III. Most BrdU-labelled cells
      were mature hepatocytes in group I, whereas in group III they appeared to be less
      mature. In group I, apoptosis showed an increase at around 24 hours, but appeared
      in group III as early as 12 hours after treatment and persisted through 48 hours.
      The expression of c-myc and c-fos were also different between the experimental
      groups. The expression intensity of c-myc in group I was highest at 1 hour and
      decreased thereafter. In groups II and III, the expressions were much more
      intense than in group I, except at 1 hour, and the increased intensity persisted
      throughout the experiment. Group II in particular showed a peak intensity at 30
      minutes and at 6 hours after treatment. In group I, c-fos was strongly expressed
      only at 24 hours, but in group III, there was progressively increased expression
      with peak intensity at 24 hours. TGF-alpha was expressed in similar intensities
      in all groups throughout the experiment. These results suggest that AFB1 may
      evoke an intense and protracted expression of c-myc, provocating the CCl4-induced
      necrosis of hepatocytes, and a prolonged expression of c-fos, including
      persistent signals for regeneration which in turn may activate the replication of
      immature cells. These findings will aid further investigation of molecular
      biologic and histologic characteristics of the hepatotoxic and hepatocarcinogenic
      mechanism of AFB1 in rats. And these results in rats, together with clinico
      epidemiologic and molecular biologic investigations in humans and other animals,
      suggest that AFB1 may supply hepatocarcinogenic background in early exposure time
      in AFB1-contaminated areas of China and Korea.

PMID- 9259618
TI  - Seroreactivities of proteinases of Candida albicans, C. tropicalis, and C.
      parapsilosis in sera from various Candida species-infected mice.
AB  - From the culture filtrates of C. albicans, C. tropicalis and C. parapsilosis,
      proteinases were purified using a series of chromatographic steps consisting of
      DEAE-Sepharose, Sephacryl S-200 and size-exclusion HPLC which removed
      contaminating mannoproteins and extraneous proteins. Anti-Candida proteinase
      antibodies in sera from mice infected with various Candida species were detected
      using ELISA for serodiagnosis of candidiasis. Three proteinases were blotted by
      homologous and heterologous anti-proteinase antisera on Western blot analysis.
      All sera from six Candida species-infected mice were reactive with proteinases of
      C. albicans, C. tropicalis, and C. parapsilosis, although C. glabrata, C.
      guilliermondii, and C. krusei did not secrete proteinase. The seroreactivities of
      proteinase with sera from mice infected with homologous C. albicans and C.
      tropicalis were higher than those with sera from heterologous Candida species
      infected mice. These results suggest that three proteinases have at least one
      common epitope, but its application for diagnosis of candidiasis should be
      considered with limits of specificity.

PMID- 9259619
TI  - Myxoma: life-threatening benign nonepithelial tumor of the larynx.
AB  - Myxoma is a rare nonepithelial neoplasm of the larynx frequently misdiagnosed as
      a large vocal polyp due to its slow-growing nature. Myxoma is a benign but often
      infiltrating neoplasm of uncertain mesenchymal cell origin, characterized by
      irregular round, spindle or stellate cells within a matrix containing abundant
      mucoid material, scant vascularity and a variable meshwork of reticulum and
      collagen. We report one case of myxoma with life-threatening dyspnea requiring
      tracheotomy.

PMID- 9259620
TI  - Bilateral coronary arteriovenous fistula coexistent with atrial septal defect and
      pulmonary stenosis.
AB  - A coronary arteriovenous fistula consists of a communication between a coronary
      artery and a cardiac chamber, a great artery or the vena cava. It is the most
      common anomaly that can affect coronary perfusion. Bilateral involvement of
      coronary fistula, however, constitutes an uncommon subgroup of coronary
      arteriovenous fistulas. We report a case which shows a rare occurrence of
      bilateral coronary arteriovenous fistula coexistent with atrial septal defect and
      pulmonic stenosis.

PMID- 9259621
TI  - Processing of English inflectional morphology.
AB  - The present paper explores the representation of inflectional morphology in the
      English lexicon. There has been a long-standing debate about how these
      inflectional relationships might be involved during on-line processing. Inflected
      forms may be derived from an uninflected base form by rule application; by
      contrast, both regular and irregular inflection may be treated in the same way,
      with morphological patterns emerging from mappings between base and inflected
      forms. The present series of experiments investigated these issues using a
      lexical decision task. The first experiment showed that response latencies to
      nouns were significantly shorter than those to verbs. A possible explanation for
      these results can be found in differences in inflectional structure between
      English nouns and verbs. Namely, the relative frequency of uninflected compared
      with inflected forms is greater for nouns than for verbs. Two additional
      experiments compared noun stimuli with different inflectional structures. In all
      cases, differences in response latencies were predicted by the frequency of the
      surface form, whether uninflected or inflected. The pattern of results lends
      support for a unitary associative system for processing regular inflection of
      nouns in English and argues against the view that regular inflected plurals are
      derived by rule from a single, uninflected lexical entry.

PMID- 9259622
TI  - The role of verb tense and verb aspect in the foregrounding of information during
      reading.
AB  - In three experiments, we explored the role of verb tense and verb aspect in
      subjects' construction of mental models while reading. In the first and second
      experiments, subjects read paragraphs in which verb tense was manipulated to
      assign current and past attributes (job descriptions) to a main character. The
      results showed that on-line accessibility was faster for current attributes. The
      results of the third experiment showed that verb aspect manipulations regarding
      character actions affect the speed at which the characters are available for
      recognition.

PMID- 9259623
TI  - Masked orthographic priming in bilingual word recognition.
AB  - Two lexical decision experiments tested the influence of briefly presented
      orthographically related primes on target word recognition in bilinguals. The
      prime stimuli were high-frequency words either from the same language as that of
      the target or from the other language known by the bilingual subjects. When the
      prime and target were from the same language, orthographically related primes
      systematically inhibited target word recognition, whereas orthographically
      dissimilar primes did not. When the prime and target were words from different
      languages, the amount of inhibition increased as a function of subjects' level of
      proficiency in the prime word's language, with highly proficient bilinguals
      showing practically equivalent amounts of within and across language inhibitory
      priming. These results strongly suggest that a printed string of letters can
      simultaneously activate lexical representations in both of the bilingual's
      languages (insofar as these share the same alphabet), even when subjects are
      performing a monolingual task.

PMID- 9259624
TI  - The syllable's role in word naming.
AB  - In a series of experiments, the masked priming paradigm with very brief prime
      exposures was used to investigate the role of the syllable in the production of
      English. Experiment 1 (word naming task) showed a syllable priming effect for
      English words with clear initial syllable boundaries (such as BALCONY), but no
      effect with ambisyllabic words targets (such as BALANCE, where the /l/belongs to
      both the first and the second syllables). Experiment 2 failed to show such
      syllable priming effects in the lexical decision task. Experiment 3 demonstrated
      that for words with clear initial syllable boundaries, naming latencies were
      faster only when primes formed the first syllable of the target, in comparison
      with a neutral condition. Experiment 4 showed that the two possible initial
      syllables of ambisyllabic words facilitated word naming to the same extent, in
      comparison with the neutral condition. Finally, Experiment 5 demonstrated that
      the syllable priming effect obtained for CV words with clear initial syllable
      boundaries (such as DIVORCE) was not due to increased phonological and/or
      orthographic overlap. These results, showing that the syllable constitutes a unit
      of speech production in English, are discussed in relation to the model of
      phonological and phonetic encoding proposed by Levelt and Wheeldon (1994).

PMID- 9259625
TI  - The phonological loop model of working memory: an ERP study of irrelevant speech
      and phonological similarity effects.
AB  - The phonological loop model for retention of auditory verbal material in working
      memory, developed by Baddeley, assumes that irrelevant speech and phonological
      similarity influence only one and the same element of the system--that is, the
      phonological short-term store. We tested this idea by recording event-related
      potentials (ERPs) to auditorily presented letters that were phonologically
      similar or dissimilar and were to be memorized in the presence of more or less
      disturbing irrelevant speech. Irrelevant speech and phonological similarity
      caused ERP effects with clearly different scalp topographies, indicating that
      these factors influence different brain systems and hence probably different
      cognitive elements. Moreover, ERPs indicated that the phonological similarity
      effect might involve processes at the level of phonological analysis. Our data
      also support recent suggestions that the irrelevant speech effect is not based on
      the phonological similarity between relevant and irrelevant material, but on the
      phonological variability within the irrelevant stream.

PMID- 9259627
TI  - The effect of line configuration on perceived numerosity of dotted lines.
AB  - Estimates the number of objects in a line are made in many different situations.
      This paper demonstrates that besides the actual number of dots, aspects of line
      configuration affect the perceived numerosity of dotted lines. Experiment 1
      provides evidence that the highly studied "clutter effect" in distance perception
      research replicates to the numerosity domain so that lines made up of more
      segments are perceived to contain more dots. Experiments 2-5 provide nomological
      validity for the recently proposed "direct distance" effect in distance
      perceptions by showing that numerosity perceptions are higher the greater the
      euclidean length between the line end points and by manipulating euclidean length
      in three orthogonal ways: the relative length of segments (Experiment 2), the
      angle between segments (Experiment 3), and the general direction of segments
      (Experiment 4). Experiment 5 conceptually replicates the results of Experiments 2
      4 utilizing stimuli-based versus memory-based judgments and a discrimination
      task. Experiments 6 and 7 extend the research on spatial perception by
      demonstrating that the use of euclidean length as a source of information is
      inversely related to line width, with width varied through clutter (Experiment 6)
      and total line length (Experiment 7). Overall, the results demonstrate that the
      robustness of the euclidean length effect is contingent on the salience of
      alternative spatial heuristics--specifically, euclidean width. Theoretical
      implications are discussed.

PMID- 9259626
TI  - The representation of nonstructural information in visual memory: evidence from
      image combination.
AB  - Two experiments investigated the differential representation of the figure and
      ground of a picture in visual short-term and long-term memory. It is known
      (Hitch, Brandimonte, & Walker, 1995) that subjects find it more difficult to
      combine mental images of two separately presented pictures in order to identify a
      novel form when the two pictures are incongruent in color (i.e., when a black-on
      white line drawing has to be combined with a white-on-black drawing). In the
      present experiments, the figures were depicted in solid form to allow color
      congruity to be varied independently for figure and ground. Results showed a
      clear impairment in image combination when the to-be-combined figures were
      incongruent in color (black-on-gray and white-on-gray) but not when their grounds
      were incongruently colored (gray-on-black and gray-on-white). In this way, image
      combination was seen to be supported by a representation of the object depicted
      in the picture rather than by a literal representation of the picture itself
      (i.e., a pictorial code). In line with previous findings, the same representation
      was seen to support image combination based on short-term memory (Experiment 1)
      and long-term memory (Experiment 2), provided that in the latter case verbal
      recoding was precluded. When verbal recoding was allowed, image combination based
      on long-term memory was insensitive to color congruity, implying the involvement
      of a more abstract structural representation.

PMID- 9259628
TI  - The nature of memory processes underlying recognition judgments in the process
      dissociation procedure.
AB  - The hypothesis is tested that the memory processes involved in recognition
      judgments in the process dissociation procedure are the same as those involved in
      standard source-monitoring tasks. It is shown how source-monitoring response
      categories can be mapped onto process dissociation response categories. On the
      basis of this abbreviation, an experiment was conducted in which it was possible
      to compare, using a multinomial modeling approach, the parameters representing
      memory processes in the process dissociation procedure with those involved in
      source monitoring. For the two different encoding conditions realized, the
      results are compatible with the hypothesis that the same processes are involved
      in source monitoring and in recognition judgments in the process dissociation
      procedure. Implications for the interpretation of the model's parameters are
      discussed.

PMID- 9259629
TI  - Recognition of music in long-term memory: are melodic and temporal patterns equal
      partners?
AB  - The notion that the melody (i.e., pitch structure) of familiar music is more
      recognizable than its accompanying rhythm (i.e., temporal structure) was examined
      with the same set of nameable musical excerpts in three experiments. In
      Experiment 1, the excerpts were modified so as to keep either their original
      pitch variations, whereas durations were set to isochrony (melodic condition) or
      their original temporal pattern while played on a single constant pitch (rhythmic
      condition). The subjects, who were selected without regard to musical training,
      were found to name more tunes and to rate their feeling of knowing the musical
      excerpts far higher in the melodic condition than in the rhythmic condition.
      These results were replicated in Experiment 2, wherein the melodic and rhythmic
      patterns of the musical excerpts were interchanged to create chimeric mismatched
      tunes. The difference in saliency of the melodic pattern and the rhythmic pattern
      also emerged with a music-title-verification task in Experiment 3, hence
      discarding response selection as the main source of the discrepancy. The lesser
      effectiveness of rhythmic structure appears to be related to its lesser encoding
      distinctiveness relative to melodic structure. In general, rhythm was found to be
      a poor cue for the musical representations that are stored in long-term memory.
      Nevertheless, in all three experiments, the most effective cue for music
      identification involved the proper combination of pitches and durations.
      Therefore, the optimal code of access to long-term memory for music resides in a
      combination of rhythm and melody, of which the latter would be the most
      informative.

PMID- 9259630
TI  - Response-to-stimulus interval does not affect implicit motor sequence learning,
      but does affect performance.
AB  - Nissen and Bullemer (1987) reported that implicit motor sequence learning was
      disrupted by the addition of a secondary task. They suggested that this effect
      was due to attentional load that the secondary task adds. Recently it has been
      suggested that the attentional load is not critical, but rather that the
      secondary task affects timing, either by lengthening or by making inconsistent
      the response-to-stimulus interval (RSI)--that is, the delay between when a
      subject makes a response and when the next stimulus appears. In six experiments
      we manipulated the RSI and found no support for these two hypotheses. An
      inconsistent RSI did not adversely affect implicit motor sequence learning. A
      long RSI did not affect learning, although under some conditions subjects did not
      express learning if the RSI was long. These results are interpreted as reflecting
      the effects of attention.

PMID- 9259631
TI  - Standardized stimuli and procedures for investigating the retrieval of lexical
      and conceptual knowledge for actions.
AB  - We have developed a set of naming and recognition tests for evaluating the
      retrieval of lexical and conceptual knowledge for actions. As a first step,
      normative information about 280 items was collected for the following variables:
      (1) the naming responses elicited by each item, (2) the degree to which the image
      of each item agreed with a target name, (3) the familiarity to each depicted
      action, and (4) the visual complexity of each item. This information was used to
      develop administration and scoring procedures for a standardized test of action
      naming. The effectiveness and reliability of these procedures were evaluated in a
      second experiment. In a third experiment, five tests were developed to probe the
      retrieval of conceptual knowledge: (1) independently of the production of a
      naming response, (2) in response to pictorial and nonpictorial stimuli, (3) in
      terms of the attributes associated with specific actions, and (4) in terms of
      similarities and differences between various actions.

PMID- 9259632
TI  - The coincidence effect in similarity and choice.
AB  - Medin, Goldstone, and Markman (1995) recently described a series of parallel
      effects in similarity and choice. They suggested that similarity and choice are
      related in a nontrivial way such that choice may entail a similarity judgment to
      an explicit or constructed ideal. In this paper, the correspondences between
      similarity and choice were investigated with respect to a phenomenon in
      similarity known as the coincidence effect. In coincidence (pronounced "coincide
      ence"), two items that match on one dimension but have a large difference on
      another dimension receive a higher similarity rating than do two items that have
      only modest differences on both dimensions. We conducted five experiments in
      order to examine commonalities between similarity and choice processes with
      respect to coincidence. Four types of tasks were given: similarity ratings,
      desirability ratings, forced choice similarities (which of two items is most
      similar to a target), and forced choice preferences (which of two items one would
      prefer, given a target). We found a main effect for ratings as opposed to forced
      choices, with ratings showing greater coincidence effects than did choices.
      Similarity measures tended to produce more coincidence than did preference
      measures. The overall pattern of results suggests the presence of dimensional
      weighting processes sensitive to task characteristics and operating somewhat
      differently for similarity and decision making.

PMID- 9259633
TI  - Lightness, equivalent backgrounds, and anchoring.
AB  - Observers compared two center/surround configurations haploscopically. One
      configuration consisted of a standard surface surrounded by two, three, or four
      surfaces, each with a different luminance. The other configuration consisted of a
      comparison surface surrounded by a single annulus that varied in luminance.
      Center surfaces always had the same luminance but only appeared to have the same
      lightness with certain annuli (equivalent backgrounds). For most displays, the
      luminance needed to obtain an equivalent background was close to the highest
      luminance in the standards surround configuration. Models based on the space
      average luminance or the space-average contrast of the standard surround
      configuration yielded poorer fits. Implications for computational models of
      lightness and for candidate solutions to the anchoring problem are discussed.

PMID- 9259634
TI  - Binaural additivity of loudness in children and adults.
AB  - Thirty-six different binaural noises were formed by crossing six right-ear
      intensities of a broadband noise with the same six intensities in the left ear in
      a 6 X 6 factorial design. Children (6-7 years of age) and adults were presented
      with 2 of these 36 binaural noises on a trial and asked to indicate which noise
      was louder. In Experiment 1, the left- and right-ear noises were in phase and
      differed only in intensity. In Experiment 2, the left- and right-ear noises were
      in opposite phase. For both the children and adults in Experiments 1 and 2, the
      paired comparison judgments of binaural loudness were shown to satisfy the
      testable axioms of conjoint measurement (transitivity and double cancellation),
      permitting the determination of interval scales of loudness for the left ear,
      right ear, and the sum of the two ears. Power functions provided a good
      description of the relation between loudness and sound pressure for the left and
      right ears of both children and adults. For both adults and children, an
      examination of the pattern of differences in judgments between Experiments 1 and
      2 indicated that, when the noises were in phase, the contribution of the right
      ear to fused loudness was greater than when the noises were presented in
      counterphase.

PMID- 9259635
TI  - Agonistic sensory effects of airborne chemicals in mixtures: odor, nasal
      pungency, and eye irritation.
AB  - Thresholds responses of odor, nasal pungency (irritation), and eye irritation
      were measured for single chemicals (1-propanol, 1-hexanol, ethyl acetate, heptyl
      acetate, 2-pentanone, 2-heptanone, toluene, ethyl benzene, and propyl benzene)
      and mixtures of them (two three-component mixtures, two six-component mixtures,
      and one nine-component mixture). Nasal pungency was measured in subjects lacking
      a functional sense of smell (i.e., anosmics) to avoid interference from
      olfaction. Various degrees of stimulus agonism (additive effects) were observed
      for each of the three sensory channels when testing mixtures. As the number of
      components and the lipophilicity of such components in the mixtures decreased, so
      did the degree of agonism. Synergistic stimulus agonism characterized the eye
      irritation response for the most complex (the nine-component) and the most
      lipophilic (one of the six-component) mixtures. Physicochemical properties play a
      large role in the determination of sensitivity to airborne chemicals,
      particularly to their ability to evoke irritation. While this has revealed itself
      previously with respect to single chemicals, it seems to have relevance to
      mixtures as well.

PMID- 9259636
TI  - The encoding of rate and talker information during phonetic perception.
AB  - The acoustic structure of the speech signal is extremely variable due to a
      variety of contextual factors, including talker characteristics and speaking
      rate. To account for the listener's ability to adjust to this variability, speech
      researchers have posited the existence of talker and rate normalization
      processes. The current study examined how the perceptual system encoded
      information about talker and speaking rate during phonetic perception.
      Experiments 1-3 examined this question, using a speeded classification paradigm
      developed by Garner (1974). The results of these experiments indicated that
      decisions about phonemic identity were affected by both talker and rate
      information: irrelevant variation in either dimension interfered with phonemic
      classification. While rate classification was also affected by phoneme variation,
      talker classification was not. Experiment 4 examined the impact of talker and
      rate variation on the voicing boundary under different blocking conditions. The
      results indicated that talker characteristics influenced the voicing boundary
      when talker variation occurred within a block of trials only under certain
      conditions. Rate variation, however, influenced the voicing boundary regardless
      of whether or not there was rate variation within a block of trials. The findings
      from these experiments indicate that phoneme and the rate information are encoded
      in an integral manner during speech perception, while talker characteristics are
      encoded separately.

PMID- 9259637
TI  - The organization of multidimensional selection on the basis of color and shape:
      an event-related brain potential study.
AB  - In this paper, we examine whether color and shape, tied to a single object in
      space, (1) are identified and selected in series or in parallel, (2) are
      identified and selected in a dependent, self-terminating manner or in an
      independent and exhaustive manner, and (3) are conjoined by a feature integration
      process before or only after an initial stage of separate attribute analyses has
      finished. We measured response time and the selection negativity (SN) derived
      from event-related brain potentials when participants responded to a unique
      conjunction of color and shape in a go/no-go target detection task. The
      discriminability of the color and the shape of the conjunction was manipulated in
      three conditions. When color and shape were easy to discriminate, the SNs to
      color and shape started at the same time. When one attribute was less
      discriminable the SN to that attribute started later, but not the SN to the
      complementary attribute. This suggests that color and shape are identified and
      selected in parallel. In all three discriminability conditions, the SNs to color
      and shape were initially independent but later interacted. This suggests that
      color and shape are initially selected independently and exhaustively, after
      which their conjunction is analyzed. The SN to local shape features started later
      than that to the conjunction of color and global shape features, which suggests
      that feature integration can start before the analyses of the separate attributes
      have finished.

PMID- 9259638
TI  - Is visual attention automatically attracted to one's own name?
AB  - Subjects were presented with briefly exposed visual displays of words that were
      common first names with a length of four to six letters. In the main experiment,
      each display consisted of four words: two names shown in red and two shown in
      white. The subject's task was to report the red names (targets), but ignore the
      white ones (distractors). On some trials the subject's own name appeared as a
      display item (target or distractor). Presentation of the subject's name as a
      distractor caused no more interference with report of targets than did
      presentation of other names as distractors. Apparently, visual attention was not
      automatically attracted by the subject's own name.

PMID- 9259639
TI  - Range of acceptable stimulus intensities: an estimator of dynamic range for
      intensive perceptual continua.
AB  - The dynamic range (DR) of a sensory system is the span (usually given in log
      units) from the lowest to highest intensities over which a continuously graded
      response is evoked, and may be a distinctive feature of each such system.
      Teghtsoonian (1971) proposed that, although DR varies widely over sensory
      systems, its subjective size (SDR) is invariant. Assuming the psychophysical
      power law, the exponent for any continuum is given by the ratio of subjective
      span to DR, both quantities expressed logarithmically. Thus, exponents are
      inversely related to the DR and many be interpreted as indexes of it. Because DR
      can be difficult or even dangerous to measure directly, we sought to define a
      smaller range representing some fixed proportion of DR that could be used in its
      place to test the hypothesis of an invariant subjective range. Observations
      manipulated the intensities of five target continua to produce the broadest range
      they found acceptable and reasonably comfortable, a range of acceptable stimulus
      intensities (RASIN). Combined with an assumed constant SDR (derived from previous
      research), RASINs accurately predicted exponents obtained by magnitude production
      from the same observers on the five continua, as well as exponents reported in
      the literature.

PMID- 9259641
TI  - Offset transients modulate attentional capture by sudden onsets.
AB  - Recent research with visual search tasks has suggested that stimuli which appear
      as sudden onsets (new objects) have attentional priority over stimuli that are
      created by removing segments of premasks (non-onset stimuli). Attentional capture
      by sudden onsets occurs despite the fact that the appearance of these new objects
      predicts neither the identity nor the location of the target in the visual search
      task. In three experiments, we examined the extent to which attentional capture
      by sudden onsets could be modulated by offset transients used to create non-onset
      objects. To that end, we systematically manipulated the ratio of non-onset to
      onset stimuli in the display (display ratio) as well as the ratio offset to onset
      segments between the stimulus types (stimulus ratio). Increases in either the
      stimulus ratio or the display ratio resulted in increases in the visual search
      for the onset targets. These results suggest that the ability of sudden onsets
      (new objects) to capture attention is influenced by stimulus-driven factors, such
      as environmental change. Interestingly, the results also indicated that goal
      directed or purposeful search for sudden-onset (new object) targets was
      relatively uninfluenced by the amount of change in the visual display. Therefore,
      it would appear that environment change has differential effects on goal-directed
      and stimulus-driven search. These results are discussed in terms of their
      implications for our understanding of attentional capture.

PMID- 9259640
TI  - Intrinsic fO differences in spoken and sung vowels and their perception by
      listeners.
AB  - We explore how listeners perceive distinct pieces of phonetic information that
      were conveyed in parallel by the fundamental frequency (fO) contour of spoken and
      sung vowels. In a first experiment, we measured differences in fO of /i/ and /a/
      vowels spoken and sung by unselected undergraduate participants. Differences in
      "intrinsic fO" (with fO of /i/ higher than of /a/) were present in spoken and
      sung vowels; however, differences in sung words were smaller than those in spoken
      vowels. Four experiments tested a hypothesis that listeners would not hear the
      intrinsic fO differences as differences in pitch on the vowel, because they
      provide information, instead, for production of a closed or open vowel. The
      experiments provide clear evidence of "parsing" of intrinsic fO from the fO that
      contributes to perceived vowel pitch. However, only some conditions led to an
      estimate of the magnitude of parsing that closely matched the magnitude of
      produced intrinsic fO differences.

PMID- 9259643
TI  - Effects of perceptual context on transsaccadic visual matching.
AB  - Transsaccadic visual matching refers to the phenomenon in which presaccadic
      signals at the location of the sacccade goal influence the visibility of
      postsaccadic test signals presented at the fovea (Juttner & Rohler, 1993). The
      present study uses variations of the perceptual context, provided by the
      structure of the presaccadic stimulus display, to investigate the influence of
      spatial information, decision factors, and visual attention on this form of
      transsaccadic information processing. The experiments yielded the following
      results: First, analysis of the data in terms of signal detection theory revealed
      that transsaccadic visual matching manifests in a shift of decision criterion
      (beta) rather than in a change of sensory sensitivity (d'). The criterion shift
      leads to a suppression of postsaccadic stimulus information that is incompatible
      with presaccadic processed information. Second, the matching effect strongly
      depends on the structure of the presaccadic display, which suggests that
      mechanisms of visual attention provide the spatial binding of pre- and
      postsaccadic stimulus information. Third, transsaccadic matching is
      phenomenologically tied to the execution of the saccade and effective during a
      postsaccadic period extending up to 160 msec after termination of the eye
      movement. These findings indicate a form of context-sensitive evaluation process
      that could subsidize the maintenance of visual stability.

PMID- 9259642
TI  - Facial inversion effects: parts and whole relationship.
AB  - "Facial inversion effects" refers to the findings that recognition of inverted
      faces is less accurate than recognition of upright faces. We now report inversion
      effects for isolated facial features: forehead, eyes, nose, mouth, and chin. This
      shows that configurational information extracted from a whole face (i.e., from
      spatial relationships among the facial features) is not necessary for obtaining
      the inversion effects. Other factors, such as "upright-orientation," mental
      rotation, and feature saliency, account for the inversion effects both in a whole
      face and in its isolated features. We propose a simple formula that
      satisfactorily predicts the recognition of a whole face and the inversion effects
      for that face on the basis of its individual features.

PMID- 9259644
TI  - A signal detection theory analysis of gap detection in the rat.
AB  - An innocuous sensory event (a prestimulus) briefly preceding a startle-eliciting
      stimulus (SES) reduces the amplitude of the elicited reflex. This study used
      signal detection theory (SDT) techniques to quantify the effects of gaps (pauses
      in otherwise continuous noise) on the rat's acoustic startle reflex. Sixteen rats
      were given four identical test sessions consisting of the randomized presentation
      of 150 trials of the SES alone and 150 trials of a gap-and-SES combination. Gap
      duration (1, 2, 4, and 8 msec) varied between sessions. Data analyses based on
      amplitude, difference scores, percentage scores, and SDT techniques identified
      similar patterns. The three longest gaps, but not the shortest, were reliably
      detected, and differences among these three were identified with percentage and
      SDT analyses. Analyses of amplitude changes over test sessions yielded different
      patterns for each measure. The results demonstrate that an SDT analysis is a
      sensitive index of prestimulus effects.

PMID- 9259645
TI  - Measures of perceived linear size, sagittal motion, and visual angle from optical
      expansions and contractions.
AB  - Using monocular observation, open-loop measurements were obtained of the
      perceptions of linear size, angular size, and sagittal motion associated with the
      terminal (largest or smallest) stimuli of repetitive optical expansions and
      contractions using 1-D or 2-D displays produced on a video monitor at a constant
      distance from the observer. The perceptions from these dynamic conditions were
      compared with those from static conditions in which the stimuli were of the same
      physical size and at the same physical distance as the terminal dynamic stimuli,
      but that were not part of the optical expansions or contractions. One result, as
      expected, was that the measures of perceived linear and angular size differed,
      but also, unexpectedly, some substantial errors were associated with the measures
      of perceived angular size. Another result was that the amount of size constancy
      was considerably less than was expected from the obtained amount of perceived
      motion in depth. Consistent with the latter result, it was found that the size
      distance invariance hypothesis (SDIH), using the physical visual angles of the
      terminal stimuli, predicted only about half of the perceived motion in depth
      obtained with the dynamic changes. Using the obtained measures of perceived
      visual angles in the SDIH increased rather than decreased the error in predicting
      the amount of motion in depth as perceived. An additional experiment suggests
      that at least some of the error in the measurement of the perceived visual angle
      is a consequence of error in the perceived origin of the visual angles. The
      absence of the expected relation between size constancy and perceived motion in
      depth in the dynamic conditions is hypothesized to be due to cognitive processes
      associated with off-sized perceptions of the stimuli.

PMID- 9259646
TI  - Can we treat coronary artery disease with antibiotics?

PMID- 9259647
TI  - Reversibility of rise in Russian mortality rates.

PMID- 9259648
TI  - Screening babies for vesicoureteric reflux.

PMID- 9259649
TI  - BCG vaccination and atopy--unfinished business?

PMID- 9259650
TI  - Endothelin antagonists in renal disease.

PMID- 9259651
TI  - Huge variation in Russian mortality rates 1984-94: artefact, alcohol, or what?
AB  - BACKGROUND: According to published data, between 1984 and 1994 mortality rates in
      Russia initially underwent a rapid decline followed by an even steeper increase.
      In 1994, male life expectancy at birth was 57.6 years, having fallen by 6.2 years
      since 1990. There has been concern that such striking fluctuations in mortality
      are an artefact, although, among other factors, alcohol consumption has been
      implicated. METHODS: We analysed the age-specific and cause-specific patterns of
      mortality decrease and increase by use of data from a newly reconstructed
      mortality series for Russia so that we could examine the plausibility of various
      explanations for the mortality trends. FINDINGS: All major causes of death, with
      the exception of neoplasms, showed declines in mortality between 1984 and 1987
      and increases between 1987 and 1994. In relative terms, these tended to be
      largest for the age-group 40-50 years; surprisingly, they were of the same
      magnitude among women and men. The largest declines and subsequent increases in
      proportional terms were observed for alcohol-related deaths and accidents and
      violence. However, pronounced effects were also seen for deaths from infections,
      circulatory disease, and respiratory disease. No substantial variations were seen
      for neoplasms. INTERPRETATION: The stability of mortality from neoplasms in
      contrast to other causes over the period 1984-94 largely precludes the
      possibility that the changes in life expectancy are mainly an artefact,
      particularly one due to underestimation of the population. Although factors such
      as nutrition and health services may be involved, the evidence is that
      substantial changes in alcohol consumption over the period could plausibly
      explain the main features of the mortality fluctuations observed. These results
      provide a major challenge to public health in Russia and to our understanding of
      the determinants of alcohol consumption and its role in explaining mortality
      patterns within and between many other countries.

PMID- 9259652
TI  - Randomised double-blind trial of fixed low-dose warfarin with aspirin after
      myocardial infarction. Coumadin Aspirin Reinfarction Study (CARS) Investigators.
AB  - BACKGROUND: Antiplatelet therapy with aspirin and systematic anticoagulation with
      warfarin reduce cardiovascular morbidity and mortality after myocardial
      infarction when given alone. In the Coumadin Aspirin Reinfarction Study (CARS),
      we aimed to find out whether a combination of low-dose warfarin and low-dose
      aspirin would give superior results to standard aspirin monotherapy without
      excessive bleeding risk. METHODS: We used a randomised double-blind study design.
      At 293 sites, we randomly assigned 8803 patients who had had myocardial
      infarction, treatment with 160 mg aspirin, 3 mg warfarin with 80 mg aspirin, or 1
      mg warfarin with 80 mg aspirin. Patients took a single tablet daily, and attended
      for prothrombin time (PT) measurements at weeks 1, 2, 3, 4, 6, and 12, and then
      every 3 months. Patients were followed up for a maximum of 33 months (median 14
      months). FINDINGS: The primary event was first occurrence of reinfarction, non
      fatal ischaemic stroke, or cardiovascular death. 1-year life-table estimates for
      the primary event were 8.6% (95% CI 7.6-9.6) for 160 mg aspirin, 8.4% (7.4-9.4)
      for 3 mg warfarin with 80 mg aspirin, and 8.8% (7.6-10) for 1 mg warfarin with 80
      mg aspirin. Primary comparisons were done with all follow-up data. The relative
      risk of the primary event for the 160 mg aspirin group compared with the 3 mg
      warfarin with 80 mg aspirin group was 0.95 (0.81-1.12, p = 0.57). For spontaneous
      major haemorrhage (not procedure related), 1-year life-table estimates were 0.74%
      (0.43-1.1) in the 160 mg aspirin group and 1.4% (0.94-1.8) in the 3 mg warfarin
      with 80 mg aspirin group (p = 0.014 log rank on follow-up). For the 3382 patients
      assigned 3 mg warfarin with 80 mg aspirin, the INR results were: at week 1 (n =
      2985) median 1.51 (IQR 1.23-2.13); at week 4 (n = 2701) 1.27 (1.13-1.64); at
      month 6 (n = 2145) 1.19 (1.08-1.44). INTERPRETATION: Low, fixed-dose warfarin (1
      mg or 3 mg) combined with low-dose aspirin (80 mg) in patients who have had
      myocardial infarction does not provide clinical benefit beyond that achievable
      with 160 mg aspirin monotherapy.

PMID- 9259653
TI  - Screening of newborn babies for familial ureteric reflux.
AB  - BACKGROUND: Vesicoureteric reflux (VUR) is not usually diagnosed until it is
      complicated by urinary infection. Prevention probably requires diagnosis in a
      newborn baby before urinary infection occurs because the peak incidence for
      infection is in early infancy. VUR is a familial disorder. We sought to find out
      whether an at-risk group of newborn babies could be identified on the basis of
      the parents' family history. METHODS: Over a 3-year period, pregnant women
      attending the antenatal clinics of three hospitals in the northeast of England
      were screened for evidence of urinary-tract disease in themselves or their
      families with a view to eliciting a history of VUR. When a woman, her partner, or
      a member of either family had a definite (by cystography records) or probable
      positive history, we recruited the mother to our study. Renal ultrasonography and
      cystography were done on the newborn babies soon after delivery, and a
      dimercaptosuccinic acid (DMSA) radioisotope scan at 3 months was done on those
      with VUR. FINDINGS: The estimated number of deliveries during the study period
      was 34,555; 20,891 women were screened; and 211 were recruited and delivered. The
      index cases were identified from a wide range of family relationships, though
      over half consisted of mothers and siblings, 19 babies had more than one index
      case and in 21 families there was one index for more than one baby or a link
      between families. Cystography was carried out on 186 newborn babies; 38 (20.4%)
      had VUR. The proportion of newborn babies with VUR among linked index families
      was 31%. Mothers and siblings amounted to 71% of the index cases for newborn
      babies with VUR. The difference between confirmed and assumed index cases in VUR
      prediction was not significant. The female/male sex ratio among index cases was
      more than 4, but among newborn babies with VUR it was 1.5. Renal ultrasound
      showed no correlation with VUR, and all DMSA scans but one were normal. No
      newborn baby developed complications resulting from cystography. INTERPRETATION:
      The screening of pregnant women for familial VUR is worthwhile because the
      frequency of VUR among the newborn babies of those with such a history is
      significantly higher than in the general population (frequency of VUR 1-2%),
      particularly if the family history involves more than one member, or more than
      one generation.

PMID- 9259654
TI  - Early BCG vaccination and development of atopy.
AB  - BACKGROUND: The increase in atopic diseases may be partly explicable by a decline
      of certain infectious diseases, or changes in childhood vaccination programmes,
      or both. We investigated whether BCG vaccination against tuberculosis influences
      the development of atopy. METHODS: We did a retrospective cohort study of 216
      children with atopic heredity, born in Stockholm between 1989 and 1992, who
      received BCG vaccination when they were younger than 6 months, and 358 age
      matched controls who had not been vaccinated. Both groups attended Sachs'
      Children's Hospital, Stockholm, Sweden, during 1995-96 for assessment of atopic
      history and clinical signs of atopic disease. All children also underwent skin
      prick testing (SPT) and serum was analysed for allergen-specific IgE antibodies.
      Serum from parents was also analysed for IgE antibodies. FINDINGS: 77 (36%)
      children in the BCG group and 145 (41%) in the control group had a positive
      history or clinical signs of atopic disease. In the vaccinated group, 26 (12%)
      children had one or more positive SPT, and 61 (31%) had circulating allergen
      specific IgE antibodies, whereas in the control group, the numbers were 35 (10%)
      and 84 (27%) respectively. Atopy was confirmed by serology in parents of almost
      two-thirds of the children in each group. Other risk factors for atopic disease
      were evenly distributed between the two groups. INTERPRETATION: Early BCG
      vaccination in children with atopic heredity does not seem to affect the
      development of atopic disease before school age.

PMID- 9259656
TI  - A 32-year-old man with recurrent cholangitis.

PMID- 9259655
TI  - Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot
      Study. ROXIS Study Group.
AB  - BACKGROUND: There is serological evidence for an association between Chlamydia
      pneumoniae and coronary heart disease. We investigated the hypothesis that an
      antichlamydial macrolide antibiotic, roxithromycin, can prevent or reduce
      recurrent major ischaemic events in patients with unstable angina. METHODS: The
      effect of roxithromycin was assessed in a double-blind, randomised, prospective,
      multicentre, parallel-group, placebo-controlled pilot study of 202 patients with
      unstable angina or non-Q-wave myocardial infarction. Patients were randomly
      assigned either roxithromycin 150 mg orally twice a day (n = 102) or placebo
      orally twice a day (n = 100). The treatment was for 30 days. Patients were
      followed up for 6 months. We report the primary clinical endpoints (cardiac
      ischaemic death, myocardial infarction, and severe recurrent ischaemia), assessed
      at day 31, in 202 patients on an intention-to-treat basis. FINDINGS: A
      statistically significant reduction in the primary composite triple endpoint
      rates was observed in the roxithromycin group: p = 0.032. The rate of severe
      recurrent ischaemia, myocardial infarction, and ischaemic death was 5.4%, 2.2%,
      and 2.2% in the placebo group and 1.1%, 0%, and 0%, in the roxithromycin group,
      respectively. No major drug-related adverse effects were observed.
      INTERPRETATION: Antichlamydial antibiotics may be useful in therapeutic
      intervention in addition to standard medication in patients with coronary-artery
      disease. Large-scale trials are needed to confirm these preliminary observations.

PMID- 9259657
TI  - Evidence for circulating bufenolide in a volume-expanded patient.

PMID- 9259658
TI  - Radioiodine for non-toxic diffuse goitre.

PMID- 9259659
TI  - Skin blood flow after transdermal S-nitrosothio-acetylglucose.

PMID- 9259660
TI  - Genetic basis of bad behaviour in adolescents.

PMID- 9259661
TI  - Association between 5-HT2A gene promoter polymorphism and anorexia nervosa.

PMID- 9259662
TI  - Routine blood-gas analysis and gastric tonometry: a reappraisal.

PMID- 9259663
TI  - Nephrogenic diabetes insipidus in a patient taking cidofovir.

PMID- 9259664
TI  - Incidence of acanthamoeba keratitis associated with contact lens wear.

PMID- 9259666
TI  - Cypriot sentenced for infecting woman with HIV-1.

PMID- 9259667
TI  - Obesity.

PMID- 9259668
TI  - Role of imager in developing world.
AB  - Medical imaging in the developing world is done by radiologists trained in the
      west or in the western manner. Yet they have to practise the specialty with
      equipment that is unreliable, poorly maintained, and difficult to repair.
      Developing countries face economic hardship, and the scarcity of radiologists and
      of imaging equipment is likely to continue. If used as the first, and very often
      the only, imaging technique, ultrasound has great advantages in such settings.
      Medical schools in the developing world and WHO should support training
      programmes in clinical ultrasound, a skill that could be offered to all doctors,
      not just radiologists.

PMID- 9259669
TI  - Chronic infections and coronary heart disease: is there a link?
AB  - A large number of studies have reported on associations of human coronary heart
      disease (CHD) and certain persistent bacterial and viral infections. We review
      the epidemiological and clinical evidence on CHD and Helicobacter pylori,
      Chlamydia pneumoniae, and cytomegalovirus (CMV), as well as possible mechanisms.
      The association between CHD and H pylori may be accounted for by residual
      confounding from risk factors. Although the association between C pneumoniae and
      CHD is stronger, the sequence of infection and disease is uncertain. As regards
      CMV, a limited number of patients with classic atherosclerotic coronary artery
      disease have been studied. Further studies are needed to resolve these
      uncertainties.

PMID- 9259670
TI  - One hundred years of aspirin.

PMID- 9259671
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259672
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259673
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259674
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259675
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259676
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259677
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259678
TI  - Interpretation of IST and CAST stroke trials. International Stroke Trial. Chinese
      Acute Stroke Trial.

PMID- 9259679
TI  - The CAPTURE trial.

PMID- 9259680
TI  - Accurate red-cell folate analysis.

PMID- 9259681
TI  - Streptokinase for empyema.

PMID- 9259682
TI  - Physiology of gastric-acid secretion.

PMID- 9259683
TI  - Physiology of gastric acid secretion.

PMID- 9259684
TI  - Reduction of trachoma in absence of a disease-control programme.

PMID- 9259685
TI  - Diagnosis of gastric carcinoma in Japan and western countries.

PMID- 9259686
TI  - Diagnosis of gastric carcinoma in Japan and western countries.

PMID- 9259687
TI  - WHO rejects Taiwan as observer.

PMID- 9259688
TI  - Cervical cancer decreasing, but not everywhere.

PMID- 9259689
TI  - No bad legacy: disposable syringes fail the test.

PMID- 9259690
TI  - Egyptian mummies.

PMID- 9259691
TI  - The USRDS and its products. United States Renal Data System.

PMID- 9259692
TI  - Incidence and prevalence of ESRD. USRDS. United States Renal Data System.
AB  - The number of patients starting ESRD therapy continues to increase, although this
      report shows evidence that the incidence rates are growing at a slower pace than
      they did in earlier years. The number of patients undergoing ESRD therapy also
      continues to increase, but the rate of increase is down to 7% from 9% to 10%.
      There is some uncertainty in these estimates in part because the reporting of non
      Medicare patients has changed.

PMID- 9259693
TI  - Treatment modalities for ESRD patients. USRDS. United State Renal Data System.

PMID- 9259694
TI  - The USRDS Dialysis Morbidity and Mortality Study: Wave 2. United States Renal
      Data System.

PMID- 9259695
TI  - Patient mortality and survival. USRDS. United State Renal Data System.

PMID- 9259696
TI  - Causes of death. USRDS. United States Renal Data System.

PMID- 9259697
TI  - Renal transplantation: access and outcomes. USRDS. United States Renal Data
      System.

PMID- 9259698
TI  - Pediatric end-stage renal disease. USRDS. United States Renal Data System.

PMID- 9259699
TI  - Hospitalization. USRDS. United States Renal Data System.

PMID- 9259700
TI  - The economic cost of ESRD, vascular access procedures, and Medicare spending for
      alternative modalities of treatment. USRDS. United States Renal Data System.

PMID- 9259701
TI  - Annual facility survey of providers of ESRD therapy. USRDS. United States Renal
      Data System.

PMID- 9259702
TI  - International comparisons of ESRD therapy. USRDS. United States Renal Data
      System.

PMID- 9259703
TI  - Analytical methods. USRDS. United States Renal Data System.

PMID- 9259704
TI  - Clinical research on weight loss must also have practical application.

PMID- 9259705
TI  - The role of clinical dietitians as perceived by dietitians and physicians.
AB  - OBJECTIVE: The purpose of this study was to examine dietitians' and physicians'
      perceptions regarding the role of clinical dietitians. SUBJECTS AND DESIGN: Four
      hundred ten physicians and clinical dietitians were randomly identified from the
      American Board of Medical Specialties Directory of Board Certified Medical
      Specialists and from Michigan district dietetic association directories. A survey
      containing demographic, situational, and role and responsibility questions was
      administered. STATISTICAL ANALYSES PERFORMED: Cronbach's alpha coefficient was
      computed to determine the internal consistency of the measurement instrument. A
      series of two-tailed t tests was performed to determine between-group differences
      on the perception questions. Analysis of covariance was completed to control for
      potential confounds. chi 2 Tests were performed to determine the relationship
      among a change of diet order question and participants' occupation, area of
      specialty, and practice setting. RESULTS: Of the surveys mailed, 73% were
      returned and 58% overall were usable. The internal consistency of the measure was
      .72. Most dietitians' and physicians' responses to the role and responsibility
      questions differed significantly, with particularly large differences noted for 6
      of 10 questions; however, "total score" differences were not significant.
      Significant associations were found for the level of specialization and type of
      occupation on the change of diet order question. APPLICATION/CONCLUSIONS: Routine
      contact, communication, and interaction between physicians and dietitians are
      vital if physicians are to know dietitians' responsibilities and competencies and
      collaborate with them when providing medical nutrition therapy to patients.
      Future studies that differentiate areas of responsibility of clinical dietitians
      and inquire into dietitians' and physicians' interactions during their education
      or training may provide further insights into this topic.

PMID- 9259706
TI  - Assessment of physicians' ability to prescribe parenteral nutrition support in a
      community teaching hospital.
AB  - OBJECTIVE: To assess the knowledge and skill base of the physicians in our
      hospital in prescribing parenteral nutrition support. DESIGN: Physicians
      completed parenteral nutrition orders for three mock patients. A range of
      clinically appropriate responses was established before the survey by the
      hospital Nutrition Support Team. Each case was scored according to set criteria,
      and the three case scores were averaged to yield a total score of 0 to 100.
      SUBJECTS/SETTING: Forty-eight attending, resident, and student physicians in the
      departments of family practice, internal medicine, and general surgery in a
      community teaching hospital. STATISTICAL ANALYSIS: Student's t test was used to
      compare interval data between two groups, and analysis of variance was used to
      compare interval data among three or more groups. If Bartlett's test for
      homogeneity of variance showed differences between the groups, the Kruskal-Wallis
      one-way analysis of variance was used. If analysis of variance revealed a
      significant difference, the data were reanalyzed using three different multiple
      comparison procedures (Tukey, Scheffe, and Bonferroni) to decrease the
      possibility of a type I error. RESULTS: The mean total score was 48.6 +/- 20.8.
      Total score differed according to the number of nutrition lectures attended
      during residency. Total score tended to differ by specialty and number of
      patients treated with parenteral nutrition; however, these differences did not
      reach statistical significance. APPLICATIONS/CONCLUSIONS: This tool can be
      adapted and used by other hospitals, medical schools, and residency programs to
      assess physicians' knowledge base, design educational programs, and improve the
      parenteral nutrition ordering process.

PMID- 9259707
TI  - Incorporating fat-modified foods into a food frequency questionnaire improves
      classification of fat intake.
AB  - OBJECTIVE: To determine the extent to which incorporating fat-modified foods into
      a food frequency questionnaire influences the agreement of energy and nutrient
      estimates with estimates obtained from food records. DESIGN: Subjects completed
      four 2-day food records at 3-month intervals. At the end of the recording period,
      a food frequency questionnaire was administered to assess usual daily intake
      during the preceding year. SUBJECTS/SETTING: One hundred and three subjects
      selected from a population-based sample of adults participating in the Beaver Dam
      Eye Study. STATISTICAL ANALYSES PERFORMED: Subjects were categorized into three
      groups on the basis of their frequency of consumption of fat-modified foods. For
      each group, correlations were calculated between food record estimates and
      estimates obtained from the original food frequency questionnaire, the original
      with a low-fat option, and the fat-modified questionnaire. RESULTS: For persons
      categorized as high consumers of fat-modified foods, incorporating questions
      regarding the consumption of these products resulted in higher correlations with
      food record estimates (original vs fat-modified version) for percentage of energy
      from total fat (.32 vs .47), saturated fat (.20 vs .41), oleic acid (.32 vs .50),
      and linoleic acid (.40 vs .46). High consumers differed in several
      characteristics that could be associated with disease risk (eg, higher ratios of
      serum total cholesterol to high-density lipoprotein cholesterol). CONCLUSIONS:
      Failure to account for the consumption of fat-modified foods in epidemiologic
      studies may result in misclassification of fat exposures. Because patterns of
      misclassification could be different for those at risk for disease, results of
      epidemiologic studies could be biased if these foods are excluded. Thus,
      incorporating fat-modified foods into food frequency questionnaires will improve
      the ability of researchers to correctly classify fat exposures and to evaluate
      potentially important relationships between fat intake and disease risk.

PMID- 9259708
TI  - Fetal growth is associated positively with maternal intake of riboflavin and
      negatively with maternal intake of linoleic acid.
AB  - OBJECTIVE: To examine whether dietary factors in pregnancy are related to fetal
      growth. DESIGN: Prospective longitudinal study during pregnancy; midway through
      gestation a dietary history was obtained. SUBJECTS/SETTING: Subjects (n = 372)
      were participants in a study on maternal essential fatty acid status during
      pregnancy who did not have hypertension or any metabolic, cardiovascular,
      neurological, or renal disorder. Only pregnant white women with the intention to
      give birth in one of the three hospitals involved in the study were included. All
      three hospitals were located in the southern part of the Netherlands. STATISTICAL
      ANALYSES PERFORMED: The relation between maternal nutrition and fetal growth was
      evaluated using multiple regression analyses. RESULTS: Maternal intake of n-3
      fatty acids plus arachidonic acid and of riboflavin were associated positively
      with fetal growth. A negative relation was observed between linoleic acid intake
      and fetal growth. APPLICATIONS/CONCLUSIONS: Our data suggest that the maternal
      diet during pregnancy is associated with fetal growth. Although this relationship
      ought to be more closely investigated, our results imply that much more attention
      should be paid to an adequate maternal diet during pregnancy, especially with
      respect to riboflavin and fatty acid intake.

PMID- 9259709
TI  - Ability of the Higgins Nutrition Intervention Program to improve adolescent
      pregnancy outcome.
AB  - OBJECTIVES: To determine the extent to which birth weight can be increased and
      the risk for adverse pregnancy outcome decreased when pregnant adolescents
      participated in the Higgins Nutrition Intervention Program; and to describe the
      dietary components of the program, including their variation as a function of
      diagnosed risk for adverse pregnancy outcome. DESIGN: Retrospective cohort study
      involving review of medical charts. SUBJECTS/SETTING: Developed as an adjunct to
      routine prenatal care, the Higgins Nutrition Intervention Program consists of an
      assessment of each pregnant adolescent's risk profile for adverse pregnancy
      outcomes and an individualized nutritional rehabilitation program based on that
      profile. The intervention group for this evaluation consisted of 1,203 pregnant
      adolescents who participated in the Higgins program at the Montreal Diet
      Dispensary between 1981 and 1991. The nonintervention group consisted of a
      randomly selected group of 1,203 pregnant adolescents known not to have
      participated in the program. OUTCOMES MEASURED: Birth weight; rates of low birth
      weight, very low birth weight, preterm delivery, fetal growth retardation,
      perinatal morbidity and mortality; and maternal morbidity. STATISTICAL ANALYSIS:
      Means and proportions were used to describe risk profiles and pregnancy outcomes
      in the two groups. Analysis of covariance and logistic regression were used to
      compare pregnancy outcomes while controlling for the effect of key confounding
      variables. RESULTS: Results from multivariable analyses showed that infants in
      the intervention group weighed an average of 55 g more (P < .05) than infants in
      the nonintervention group; their low-birth-weight rate was 39% lower (P < .001)
      and their very-low-birth-weight rate was 56% lower (P < .01). Individually
      determined dietary prescriptions for the adolescents in the intervention group
      recommended increases in daily consumption averaging approximately 900 kcal
      energy and 52 g protein. The lowest daily increases (approximately 150 kcal
      energy and 2 g protein) were recommended to the group with no diagnosed risks;
      the greatest increases (approximately 1,300 kcal energy and 76 g protein) were
      recommended to the group with multiple risk conditions. Although none of the
      risk/intervention groups achieved their prescribed increases during intervention,
      increases in actual intake generally followed the pattern of the prescribed
      increases; that is, the greater the prescribed increase, the greater the actual
      increase. CONCLUSIONS: These results suggest that the Higgins Nutrition
      Intervention Program, in which nutrition intervention is individualized as a
      function of diagnosed risk, significantly improves the outcome of adolescent
      pregnancy.

PMID- 9259710
TI  - Tray service generates more food waste in dining areas of a continuing-care
      retirement community.
AB  - OBJECTIVE: To determine if the type of service system affects the amount of
      service food waste (SFW) generated in dining areas of a continuing-care
      retirement community. RESEARCH DESIGN: A waste stream analysis was conducted for
      7 days to determine quantity of SFW generated in three service systems: health
      care tray service, health care dining room with wait-staff service, and
      ambulatory dining room with family-style service. Weight and volume were
      determined. SETTING: Health care tray service and wait-staff service were
      provided to 70 residents in a health care unit. Family-style service was provided
      as an optional service for 130 residents in independent-living units. An average
      of 229 meals were served per day. STATISTICAL ANALYSIS PERFORMED: Analysis of
      variance and a multiple comparison method were used to compare mean weight and
      volume of SFW on a per meal, per day, and per week basis. RESULTS: During the 7
      day period, 482.8 lb, or 83 gal, of SFW was disposed of Health care tray service
      generated more SFW by weight for all three meals than either family-style service
      or wait-staff service, and it generated the greatest total volume of service
      waste. Residents eating in the dining room with family-style service disposed of
      significantly less SFW by weight at lunch and dinner than those receiving the
      other two service styles. APPLICATIONS: Changing the style of service can affect
      not only quantity of solid waste generated and associated disposal costs but also
      food and supply costs, meal acceptability, and quantity of natural resources
      required. The systems approach should be used to assess the feasibility of
      changing service system so that all costs are considered.

PMID- 9259711
TI  - Nutrition and health for older persons in rural America: a managed care model.
AB  - Health care services and resources for older persons living in rural areas may be
      highly variable, and integrated service-delivery models are often lacking. This
      article presents a managed-care model of nutrition risk screening and
      intervention for older persons in rural areas. Nutrition risk screening was
      implemented by the Geisinger Health Care System, Danville, Pa, to target all
      eligible enrollees in a regional Medicare risk program. A single remote clinic
      site participating in the managed health care system was chosen for further study
      of a linked screening and case-management effort for undernourished persons.
      Screening and intervention at the clinic site selected for this study were guided
      by centralized expertise and resources. Individualized evaluation and
      intervention plans were developed with the aid of a dietitian and implemented by
      the clinic case manager. Of the 417 subjects who completed screening at the
      remote site, 68 met the risk criteria for undernutrition and were selected for
      case management. Many of the targeted persons received interventions that
      included evaluations by a physician or physician extender (eg, physician
      assistant, nurse practitioner) at the clinic and consultations with nutrition,
      mental health, or social services professionals. Twenty-six of the subjects who
      took part in the intervention completed a follow-up screening 6 months later. Ten
      of those persons no longer exhibited risk criteria. This demonstrates the
      feasibility of a linked screening and case management program for nutrition risk
      in the managed-care setting.

PMID- 9259712
TI  - Integrating Hazard Analysis and Critical Control Point (HACCP) and sanitation for
      verifiable food safety.
AB  - Reliable, verifiable food safety requires the application of technologically
      correct methods in a systematic way. This requires making a distinction between
      sanitation and Hazard Analysis and Critical Control Point (HACCP) and integrating
      these two systems into one food safety system. Although sanitation and HACCP
      share the same goal of producing safe food products, the focus of sanitation is
      on the environment surrounding the food to prevent contamination, whereas the
      focus of HACCP is on controlling hazards intrinsic to food materials. Together
      they provide the organizational base for applying the correct methods and
      procedures to ensure and verify that food served is safe for foodservice clients.
      These approaches also provide records that demonstrate that food safety measures
      have been planned and completed as planned. One way to demonstrate a responsible
      approach to food safety is to understand the differences between sanitation and
      HACCP and to build approaches to food safety that use both of these systems. The
      resulting integrated system has a better chance of controlling all the hazards
      than either system by itself.

PMID- 9259713
TI  - Development of a pediatric residency program for registered dietitians.

PMID- 9259714
TI  - Withdrawal rates for infants and children participating in WIC in Maryland.

PMID- 9259715
TI  - Continuous positive airway pressure treatment results in weight less in obese and
      overweight patients with obstructive sleep apnea.

PMID- 9259716
TI  - Managed care--government style.

PMID- 9259717
TI  - A jaundiced look at the management of hepatitis?

PMID- 9259718
TI  - The ethics of physician-assisted suicide and euthanasia.

PMID- 9259719
TI  - Influenza--the forgotten vaccination.

PMID- 9259720
TI  - Rationing secondary and tertiary health care--a time for political clarity.

PMID- 9259721
TI  - Is there a crisis in academic medicine in South Africa?

PMID- 9259722
TI  - Growth monitoring--is it a task worth doing in South Africa?
AB  - Childhood undernutrition is a serious public health problem in South Africa.
      Growth monitoring (GM) is a central tool in attempts to prevent and detect
      undernutrition. Despite its widespread adoption by international and national
      agencies, there has been very little evidence which shows that it has made an
      impact in reducing undernutrition. An important problem has been the conceptual
      confusion as to the exact role of GM. This article reviews the international
      evidence for the effectiveness of GM when used in various roles and proposes some
      of the factors necessary for GM to be successful in South Africa.

PMID- 9259723
TI  - Clinical characteristics of childhood asthmatics in Johannesburg.
AB  - OBJECTIVES: To describe the clinical features of Caucasian childhood asthmatics
      in Johannesburg in order to compare these with a similar population of black
      asthmatic children resident in Soweto. DESIGN: In a prospective study, a history
      was obtained by means of an investigator-administered questionnaire. MAIN OUTCOME
      MEASURES: Presenting asthma symptoms, precipitants of symptoms, concomitant
      diagnoses, individual and family background of allergy and 'delay to diagnosis'
      of asthma (age at symptom onset subtracted from age at diagnosis) from history
      and allergen sensitivity as assessed by skin-prick tests (SPTs). RESULTS: Of the
      468 (297 boys) asthmatics studied, 456 (97.4%) presented with cough, 362 (77.3%)
      with wheeze, 286 (61.1%) with a tight chest and 277 (59.2%) with breathlessness.
      Cough as sole symptom occurred in 102 (21.8%) while only 8 (1.7%) wheezed and did
      not cough. Commonest symptom triggers were upper respiratory tract infections and
      activity/exercise. An individual atopic background was common-allergic rhinitis
      in 413 (88.2%)-as was a family history of atopy, present in 390 (83.3%).
      Prolonged symptomatic periods occurred in most patients before asthma was
      diagnosed (among children diagnosed after the age of 4 years, 50% had been
      symptomatic for more than 3 years). 'Delay to diagnosis' was not influenced by
      presenting symptoms or by previous hospitalisation for asthma. Other respiratory
      diagnoses of bronchitis and pneumonia were common, possibly because of
      misdiagnosis. Commonest allergens on SPT were corn pollen, Bermuda and 5-grass
      mix, and standardised mites. Aside from wheat, food allergy was uncommon.
      CONCLUSIONS: Cough was the commonest presenting symptom despite its still being
      regarded as a less classic symptom of asthma that may account for misdiagnosis
      and a high frequency of other respiratory diagnoses. Associated allergy,
      especially allergic rhinitis, occurred frequently. Many aspects of presentation
      in whites were similar to those in Soweto children, although the latter had a
      more frequent concomitant diagnosis of tuberculosis, and recognised dust and cold
      weather as more frequent triggers. Differences might be influenced by the care
      giving situation.

PMID- 9259724
TI  - Halothane hepatitis in a South African population--frequency and the influence of
      gender and ethnicity.
AB  - AIM: To review post-anaesthetic hepatitis in a South African population, given
      that halothane use is restricted in other countries because of the high mortality
      and morbidity of its associated type II (idiosyncratic) hepatitis, even though it
      is still widely used in South Africa. STUDY DESIGN: Descriptive, retrospective
      analysis. PATIENTS AND METHODS: Hepatitis cases that occurred after inhalational
      anaesthetic use were identified by means of a computer search of Groote Schuur
      Hospital records, 1980-1994. Cases of hepatitis caused by circulatory failure and
      viral hepatitis were excluded. RESULTS: Twenty-six episodes occurred in 22
      patients (mean age 49.05 years, range 32-65 years), of whom 15 were women. This
      gave an estimated incidence of 3.53/100,000 anaesthetics (95% confidence interval
      2.06-5.0/100,000). All had pyrexia (mean 38.7 +/- 0.72 degrees C), malaise,
      anorexia or nausea and vomiting, with onset a mean of 4.27 +/- 3.5 days after
      exposure. Jaundice occurred in 86%, rash in 13.6%; 17 patients (77%) were obese.
      Alanine and aspartate aminotransferase levels were raised 47.49 +/- 61.8 and 55.9
      +/- 54.5 times the upper limit of normal. Seven patients died and 1 underwent
      liver transplantation. Hepatitis occurred after the first exposure in only 2
      patients (9%). Men and women had a similar risk, but the estimated relative risk
      for whites v. black or coloured patients was 3.33 (95% confidence interval 1.45
      7.23; P = 0.003) controlling for gender. Awareness of the condition was
      suboptimal, and in 3 patients re-exposure to halothane occurred after an initial
      episode of typical halothane hepatitis. CONCLUSION: Halothane hepatitis remains a
      major cause of morbidity and mortality in South Africa. It is more common in
      whites, but there was no gender-related excess risk.

PMID- 9259725
TI  - Incidence and frequency rates of childhood cancer in Namibia.
AB  - OBJECTIVE: To estimate the extent of paediatric malignancy in an African country
      and to compare these findings with paediatric cancer rates in other countries.
      DESIGN: A retrospective descriptive study which calculated incidence and
      frequency rates from the data obtained from a 6-year survey of childhood cancer
      in Namibia. SETTING: Children from the general community who were referred by
      primary care physicians or clinics and diagnosed in peripheral district hospitals
      or a tertiary care institution. PATIENTS: A total of 163 children less than 15
      years of age diagnosed with any malignant neoplasm, intracranial tumour or
      histiocytosis between 1983 and 1988. INTERVENTION: None. MAIN OUTCOME MEASURES:
      The minimum overall incidence of childhood cancer recorded in Namibia was lower
      than the rates usually reported by economically privileged countries. The rates
      of certain malignancies corresponded to the rates recorded in other African
      countries. RESULTS: The overall incidence of childhood cancer was 55.5 per
      million. Tumours of the central nervous system occurred most commonly (18%),
      followed by renal tumours (14%), leukaemia (12%) and lymphoma (11.5%). The 5.8
      per million incidence rate of retinoblastoma was similar to the rates recorded in
      other African countries but higher than in the UK or the USA. The incidence rates
      per million children for renal tumours, malignant bone tumours and soft-tissue
      sarcomas were 7.4, 4.8 and 5.2, respectively, which correspond with the rates in
      Western Europe and the USA. The incidence rate of CNS tumours was only 9.3 per
      million. Both leukaemia (6.5 per million) and lymphoma (6.3 per million) had
      rates far lower than those recorded in central Africa or developed Western
      countries. CONCLUSION: The incidence pattern of childhood cancer in Namibia
      demonstrates features of both the patterns described as typical for Africa and
      those described for industrialised countries.

PMID- 9259727
TI  - Lone ventricular cardiomyopathy, 1993-1996.
AB  - OBJECTIVE: To identify subjects with univentricular idiopathic structural and/or
      functional myocardial disorders (as defined) and to describe the characteristic
      features. DESIGN: Over a period of 4 years, 1993-1996, all adult subjects were
      obtained consecutively from a centralised referral cardiological service. The
      subjects had to fulfil a set of formulated diagnostic criteria for each isolated
      type of univentricular disease-symptomatic or asymptomatic. The subjects were
      diagnosed on the basis of clinical features, supported by electrocardiographic,
      radiological and echocardiographic evidence of lone ventricular disease, with a
      further definition of abnormalities based on appropriately selected standard left
      and right heart assessments, inter alia: (i) cardiac catheterisation, including
      coronary arteriography and pulmonary angiography; (ii) radio-isotope studies
      mibiscan; (iii) ventilation perfusion scan; and (iv) laboratory tests to identify
      likely cause(s) of diffuse myocardial damage as well as to recognise nonspecific
      effects of tissue damage and organ dysfunction. SETTING: A referral cardiological
      service of a tertiary academic hospital, which provides a consultative service
      for inpatients and ambulatory cases. All subjects were studied on admission to
      hospital. PARTICIPANTS: A set of criteria was formulated for each category of
      lone ventricular myopathy. A total of 30 patients were thus identified and
      included in the study-men and women ranging in age from 18 years to 84 years,
      with an average of 48 years. All were investigated after admission to hospital by
      means of a detailed set of investigations that rigorously excluded overt or
      occult causes of diffuse myocardial damage and any severe myocardial dysfunction
      secondary to haemodynamic conditions. Seven patients with significant coronary
      artery disease were excluded. Any subject with pulmonary or systemic hypertension
      was also excluded. MAIN OUTCOME MEASURES: Total number of patients, number of
      patients in each subgroup were analysed by age, sex, clinical features, and by
      special investigation. The mode of presentation and electrocardiographic features
      were analysed separately. RESULTS: Twenty-two left ventricular and 8 right
      ventricular cases of lone ventricular cardiomyopathy were diagnosed. All but 1
      patient with right ventricular disease were symptomatic and 5 subjects with left
      ventricular myopathy were incidentally discovered. There were 17 men and 13 women
      in the series. Of the 8 patients with right ventricular disease, 6 were women,
      while of the 22 patients with left ventricular cardiomyopathy, 15 were men.
      CONCLUSION: The study supports the previously described existence of lone
      ventricular idiopathic cardiomyopathy. Further studies are, however, indicated in
      order to define its prevalence and nature more accurately, as well as to describe
      any relationship with univentricular cardiomyopathies, and define the
      characteristics of each category and the possible evolutionary patterns. Right
      ventricular cardiomyopathy is a new entity which may pose difficult diagnostic
      challenges, while left ventricular disease is generally accepted as a stage in
      the clinical spectrum of classic idiopathic dilated cardiomyopathy.

PMID- 9259726
TI  - Illicit intravenous drug use in Johannesburg--medical complications and
      prevalence of HIV infection.
AB  - OBJECTIVE: To describe the magnitude of the problem of abuse by self-injection of
      dipianone HCl/cyclizine HCl (Wellconal) and to document the associated morbidity,
      mortality and prevalence of HIV infection. DESIGN: We conducted a retrospective
      analysis of 121 admissions of 86 patients who were current intravenous Wellconal
      abusers and presented to Johannesburg and J G Strijdom Hospitals over an 18-month
      period. Case records were analysed in respect of age, sex, median hospital stay,
      complications, HIV antibody status and eventual outcome. MAIN OUTCOME MEASURES:
      Age, sex, median hospital stay, complications, HIV antibody status and eventual
      outcome. RESULTS: Complications of Wellconal abuse occurred in young adults
      (median age 24 years) with an approximately equal gender distribution. Opiate
      overdose was the most frequent presenting diagnosis (32%), followed by right
      sided endocarditis (20%) and deep-vein thrombosis (12%). A wide variety of
      complications accounted for the remaining 36%. A 2% HIV antibody positivity rate
      was found, which is substantially lower than that encountered in intravenous drug
      abusers in other parts of the world. Seventy-eight per cent of patients completed
      therapy successfully, but 19% left hospital prematurely against medical advice.
      There was a mortality rate of 3%. CONCLUSIONS: While the prevalence of Wellconal
      abuse in the broader South African community is unknown, our study draws
      attention to the extent of the problem in Johannesburg.

PMID- 9259728
TI  - Neuro-acanthocytosis--a rare cause of chorea.
AB  - Neuro-acanthocytosis is a rare neurological disorder characterised by stereotyped
      chorea, especially of the mouth, areflexia and acanthocytes seen in the
      peripheral blood. No cases have been described in the literature from South
      Africa. We report here a case of neuro-acanthocytosis seen in a black woman who
      presented to Johannesburg Hospital.

PMID- 9259729
TI  - Hilton's Rest and Pain, Guy's Hospital personalities and Guy's South African
      rugby connection.
AB  - Guy's Hospital occupies a unique position in medical history. John Hilton (1805
      1879), as anatomist, physiologist, morbid anatomist and surgeon in his classic
      Rest and Pain, published in 1863 (reissued in 1950), formulated principles for
      the diagnostic significance of pain and the value of rest in healing. An array of
      personalities graced Guy's Medical School in that era. The triumvirate of Richard
      Bright (1789-1858). Thomas Addison (1793-1860) and Thomas Hodgkin (1798-1866)
      contemporaneously discovered the diseases that bear their names. Sir Astley
      Cooper, a leading surgeon of his day (1768-1841), performed the first amputation
      of the hip joint before the era of anaesthesia. John Keats (1795-1821) qualified
      as a surgeon at Guy's but, realising his unsuitability of temperament, became a
      leading English poet. This change of direction caused him anguish and suffering,
      mainly because of the rejection of his poetry; tuberculosis led to his death in
      Rome, where he is buried. Guy's Medical School also allowed South Africans to
      enter as rugby players before the 1920s, when they were required to qualify
      overseas.

PMID- 9259730
TI  - Patients who can't afford to pay--time for a code of ethics.

PMID- 9259731
TI  - Trace elements and osteoporosis.

PMID- 9259732
TI  - HIV infection is not associated with an increased rate of drug-resistant
      tuberculosis.

PMID- 9259733
TI  - Our peripheral hospitals--crisis or opportunity?

PMID- 9259734
TI  - Our peripheral hospitals--crisis or opportunity?

PMID- 9259735
TI  - DOTS--are we over-optimistic?

PMID- 9259736
TI  - Effective asthma control--time for physician and pharmacist to join forces.

PMID- 9259737
TI  - Migrancy and HIV/STDs in South Africa--a rural perspective.

PMID- 9259738
TI  - Abortion objectors--rights and responsibilities.

PMID- 9259739
TI  - Diagnostic disagreement with malaria diagnosis in Mpumalanga.

PMID- 9259740
TI  - Impact of antimicrobial resistance and antibiotic choice on the outcome of
      pneumococcal meningitis.

PMID- 9259741
TI  - Lamotrigine and serious skin reactions.

PMID- 9259742
TI  - Private immunisation--the agony is worse than the injection.

PMID- 9259743
TI  - A 'traditional' traditional healer: Philip Kubukeli. Interview by Jonathan
      Spencer Jones.

PMID- 9259744
TI  - The end of the long-term decline in stroke mortality in the United States?

PMID- 9259745
TI  - A systems approach to immediate evaluation and management of hyperacute stroke.
      Experience at eight centers and implications for community practice and patient
      care. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA
      Stroke Study Group.
AB  - BACKGROUND AND PURPOSE: With the approval by the Food and Drug Administration of
      recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke within
      180 minutes of symptom onset, patients and prehospital and hospital systems will
      now have to treat stroke as a medical emergency. It is thus critical to develop
      efficient hospital-based methods for hyperacute stroke patient evaluation and
      intervention at both community-based and tertiary care academic centers. METHODS:
      We describe how the eight centers in the National Institute of Neurological
      Disorders and Stroke rt-PA Stroke Trial developed systems for enrolling patients
      within 3 hours of symptom onset. The actual methodology and practical sequence of
      events are detailed. Deming principles of system organization were applied, and
      each center developed a flowchart of acute stroke patient screening, assessment,
      and treatment. We divided the process into the following: clinical center
      background and preparation, screening, stroke team response, data needed before
      treatment, CT of the head, pharmacy, patient treatment, and monitored care.
      Critical features, both unique to a given center and shared by several centers
      (common at four or more centers), were summarized. RESULTS: Phase I of the trial
      included several months of preparation with review of every detail involved in
      the process of acute stroke care at each site. All centers worked closely with
      emergency medical services. Community stroke awareness and education programs
      were developed. A stroke team was initiated and worked closely with the emergency
      department physicians and nurses. Rapid and efficient communication systems and
      protocols were established to reduce time to complete each task. Standardized
      stroke examinations and protocols for blood pressure management and intracranial
      hemorrhage detection as well as nursing flowcharts were used. CONCLUSIONS:
      Hyperacute stroke treatment can be initiated, often within 55 minutes of patient
      arrival at the hospital, in both community and academic settings when all aspects
      of stroke care processes are identified, streamlined, and built into the day-to
      day operations of the prehospital and hospital healthcare delivery system.

PMID- 9259746
TI  - Assessing quality of life after stroke. The value and limitations of proxy
      ratings.
AB  - BACKGROUND AND PURPOSE: Because many stroke survivors have cognitive and
      communication disorders, self-reported information on a patient's quality of life
      (QL) cannot always be obtained. Proxy ratings may be used to prevent exclusion of
      this highly relevant subgroup of patients from QL studies. The purpose of this
      study was to evaluate both the value and possible limitations of such proxy
      ratings. METHODS: The patient sample was composed of 437 patients who had
      suffered a stroke 6 months earlier. QL was assessed by means of the Sickness
      Impact Profile (SIP). For 108 patients who were not communicative because of
      cognitive or linguistic deficits, proxy ratings on the SIP were provided by the
      patients' significant others. For 228 of the 329 communicative patients, both
      self-reported and proxy SIP ratings were obtained. RESULTS: When mean SIP scores
      for patients with both self-reported and proxy-derived data available were
      compared, the proxy mean scores were generally in close agreement with those of
      the patients. However, systematic differences were noted for several SIP scales,
      with proxies rating patients as having more QL impairments than the patients
      themselves. Intraclass correlations were moderate to high for most SIP subscales
      (average intraclass correlation coefficient [ICC] = .63), the physical (ICC =
      .85) and psychosocial dimensions (ICC = .61), and the total SIP score (ICC =
      .77). The proxy SIP scores were sensitive to differences in patients' functional
      health, which supports the validity of these ratings. For all patients combined,
      more QL impairments were found for patients with supratentorial cortical or
      subcortical infarctions and hemorrhages than for patients with lacunar
      infarctions and infratentorial strokes. Although proxy respondents were more
      frequently needed for patients with the first two types of stroke, we found no
      evidence of biased results as a consequence of an unbalanced use of proxy
      respondents across the different types of stroke. CONCLUSIONS: These results
      suggest that the benefits of using proxy ratings for noncommunicative patients
      outweigh their limitations. The findings stress the need for inclusion of this
      important subgroup of patients in QL studies. Their significant others are able
      to provide useful information on these patients' QL.

PMID- 9259747
TI  - Effects of intensity of rehabilitation after stroke. A research synthesis.
AB  - BACKGROUND AND PURPOSE: A research synthesis was performed to (1) critically
      review controlled studies evaluating effects of different intensities of stroke
      rehabilitation in terms of disabilities and impairments and (2) quantify patterns
      by calculating summary effect sizes. The influences of organizational setting of
      rehabilitation management, blind recording, and amount of rehabilitation on the
      summary effect sizes were calculated. METHODS: A Medline literature search was
      performed for a critical review of the literature. The internal and external
      validity of the studies was evaluated. In addition, a meta-analysis was performed
      by applying the fixed (Hedges's g) effects model. RESULTS: The effects of
      different intensities of rehabilitation were studied in nine controlled studies
      involving 1051 patients. Analysis of the methodological quality revealed scores
      varying from 14% to 47% of the maximum feasible score. Meta-analysis demonstrated
      a statistically significant summary effect size for activities of daily living
      (0.28 +/- 0.12). Lower summary effect sizes (0.19 +/- 0.17) were found for
      studies in which experimental and control groups were treated in the same setting
      compared with studies in which the two groups of patients were treated in
      different settings (0.40 +/- 0.19). Variables defined on a neuromuscular level
      (0.37 +/- 0.24) showed larger summary effect sizes than variables defined on a
      functional level (0.10 +/- 0.21). Weighting individual effect sizes for the
      difference in amount of rehabilitation between experimental and control groups
      resulted in larger summary effect sizes for activities of daily living and
      functional outcome parameters for studies that were not confounded by
      organizational setting. CONCLUSIONS: A small but statistically significant
      intensity-effect relationship in the rehabilitation of stroke patients was found.
      Insufficient contrast in the amount of rehabilitation between experimental and
      control conditions, organizational setting of rehabilitation management, lack of
      blinding procedures, and heterogeneity of patient characteristics were major
      confounding factors.

PMID- 9259748
TI  - Platelet activation and lipid peroxidation in patients with acute ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Both platelet activation and lipid peroxidation are
      potential sources of vasoactive eicosanoids that can be produced via the
      cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed
      peroxidation of arachidonic acid, ie, isoprostanes. We investigated the
      biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion
      of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62
      consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute
      ischemic stroke. METHODS: At least two consecutive 6-hour urine samples were
      obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids
      were measured by previously described radioimmunoassays. RESULTS: Repeated
      periods of enhanced thromboxane biosynthesis were found in 52% of patients.
      Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to
      967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors
      (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to
      2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi
      PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24
      to 570) pmol/mmol creatinine (P > .05). The correlation between the two
      metabolites was moderate in both untreated patients (r = .41, P < .001) and
      patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple
      regression analysis, increased thromboxane production was independently
      associated with severity of stroke on admission, atrial fibrillation, and
      treatment with cyclooxygenase-inhibiting drugs. CONCLUSIONS: We conclude that
      during the first few days after an acute ischemic stroke (1) platelet activation
      occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation
      is not associated with concurrent changes in isoprostane biosynthesis; (3)
      platelet activation is independently associated with stroke severity and atrial
      fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet
      cyclooxygenase activity.

PMID- 9259749
TI  - Cerebrovascular and cardiovascular measurements during neurally mediated syncope
      induced by head-up tilt.
AB  - BACKGROUND AND PURPOSE: This study examines changes in systemic hemodynamics and
      in cerebral blood velocity that occur during neurally mediated syncope (NMS) to
      determine whether cerebral autoregulation is intact or impaired in patients with
      recurrent NMS. METHODS: Beat-to-beat recordings of heart rate, blood pressure
      (volume clamp photoplethysmography), stroke volume (impedance cardiography), and
      right middle cerebral artery blood velocity (transcranial Doppler sonography)
      were performed at rest and during 80 degrees head-up tilt. Twelve patients with
      NMS and 10 healthy control subjects were studied. RESULTS: Baseline values and
      the initial response to head-up tilt of control subjects and patients with NMS
      were similar. The mean latency to onset of syncope was 11.8 +/- 11.1 minutes. At
      syncope, heart rate, systolic and diastolic blood pressure, and diastolic
      cerebral blood velocity decreased significantly, whereas systolic cerebral blood
      velocity did not change. Calculated cerebrovascular resistance was significantly
      reduced from 1.85 +/- 0.60 to 1.32 +/- 0.27 mm Hg/cm per second, whereas the
      pulsatility index increased from 0.92 +/- 0.16 to 1.52 +/- 0.21. We never
      observed a change in cerebral blood velocity before the rapid decline in blood
      pressure, nor did we observe any significant change in respiratory pattern.
      CONCLUSIONS: The decrease in cerebrovascular resistance during NMS indicates that
      the integrity of cerebrovascular autoregulation is maintained even when syncope
      is imminent. The selective loss of diastolic flow during syncope and the increase
      in pulsatility index are likely caused by collapse of downstream vessels as
      diastolic blood pressure decreases below the critical closing pressure of
      cerebral vessels.

PMID- 9259750
TI  - Cerebrovascular reactivity in comatose patients resuscitated from a cardiac
      arrest.
AB  - BACKGROUND AND PURPOSE: Cerebral blood flow after cardiac arrest is reduced
      during the delayed hypoperfusion phase, while cerebral metabolic rate of oxygen
      returns to baseline values. Hypocapnia can induce cerebral ischemia in
      neurosurgical patients who already have reduced cerebral blood flow. The purpose
      of the present study was to determine whether comatose patients resuscitated from
      a cardiac arrest have a normal cerebrovascular reactivity to changes in PaCO2 and
      whether hypocapnia causes cerebral ischemia. METHODS: We measured mean flow
      velocity (MFV) and pulsatility index (PI) in the middle cerebral artery, jugular
      bulb oxygen saturation (SjbO2), and arterial-jugular lactate difference (AJLD)
      during normo-, hypo-, and hyperventilation in 10 comatose patients resuscitated
      from a cardiac arrest. The first measurements were made within 6 hours after
      cardiac arrest and repeated 6, 12, and 24 hours later. RESULTS: During
      hypoventilation we observed a significant decrease in PI and an increase in MFV
      and SjbO2. During hyperventilation PI and MFV did not change, but SjbO2 showed a
      significant decrease. This was accompanied by an increase in AJLD, suggesting
      cerebral ischemia. In four patients the SjbO2 decreased below the ischemic
      threshold of 55%. CONCLUSIONS: The cerebrovascular reactivity to changes in
      arterial carbon dioxide tension is preserved in comatose patients resuscitated
      from a cardiac arrest. Hyperventilation may induce cerebral ischemia in the
      postresuscitation period.

PMID- 9259751
TI  - Mitral valve strands and the risk of ischemic stroke in elderly patients. The
      French Study of Aortic Plaques in Stroke (FAPS) Investigators.
AB  - BACKGROUND AND PURPOSE: Strands are thin and filamentous attachments on the
      cardiac valves shown by transesophageal echocardiography. Their nature and their
      potential for embolization are largely unknown. The objective was to estimate the
      risk of brain infarction in patients with mitral valve strands. METHODS: Using
      transesophageal echocardiography, we compared the frequency of strands on native
      mitral valves in 284 consecutive patients admitted with brain infarction and 276
      control patients, all older than 60 years. In a second part, case subjects were
      followed up over a 2- to 4-year period, and the risk of recurrence of brain
      infarction was estimated in patients with and without strands. RESULTS: In the
      case-control study, mitral valve strands were found in 22.5% of the case patients
      and in 12.1% of the control subjects. In case subjects, mitral valve strands were
      more frequent in those with mitral valve dystrophy (52.4% versus 37.4%; P = .03).
      Strands were not associated with mitral valve prolapse, annular calcifications,
      or left atrial spontaneous echocardiographic contrast. After adjustment for age,
      sex, and mitral valve dystrophy, the odds ratio for ischemic stroke among
      patients with mitral strands was 2.2 (95% confidence interval, 1.4 to 3.6; P =
      .005). The frequency of strands was not different in patients with a known cause
      of brain infarction (24.4%) from that in patients with no other apparent cause
      (20.9%). During 646 per 100 person-years of follow-up, the incidence of recurrent
      brain infarction was 6.0 person-years in patients with strands and 4.2 in those
      without. In the Cox analysis, including potential confounders and poststroke
      treatment, mitral valve strands did not appear as independent predictors of
      recurrent brain infarction (relative risk, 1.3; 95% confidence interval, 0.5 to
      3.0; P = .54). CONCLUSIONS: The present study shows an independent association
      between mitral valve strands and the risk of brain infarction. However, the lack
      of an increased relative risk of recurrence raises doubts about the potential
      causal relation with brain infarction in patients aged 60 years or older.

PMID- 9259753
TI  - Seizures in acute stroke: predictors and prognostic significance. The Copenhagen
      Stroke Study.
AB  - BACKGROUND: Despite the common occurrence of seizures during the early phase of
      stroke (ES), the effect of ES on prognosis is not known. We determined the
      relationships between ES and stroke outcome and identified predictors of ES.
      METHODS: In this community-based study, we prospectively and consecutively
      studied 1197 patients with acute stroke. We determined the number and type of
      seizures, initial stroke severity, infarct size, mortality, and outcome in
      survivors. Stroke severity was measured on admission, weekly, and at discharge
      using the Scandinavian Stroke Scale (SSS). Multiple logistic and linear
      regression outcome analyses included relevant confounders and potential
      predictors, including age, gender, stroke severity on admission, atrial
      fibrillation, ischemic heart disease, diabetes, blood glucose level on admission,
      claudication, and hypertension. RESULTS: Fifty patients (4.2%) had seizures
      within 14 days of the stroke. In the multivariate analyses, only initial stroke
      severity was related to ES; stroke type and lesion localization were not related.
      For each 10-point increase in stroke severity (SSS score), the relative risk of
      ES increased by a factor of 1.65 (95% confidence interval, 1.4 to 1.9) (P <
      .0001). ES did not influence the risk of death during hospital stay (P = .56). In
      survivors, ES was related to a better outcome, equivalent to an increased SSS
      score of 5.7 points (SE [b] = 1.8; P = .002). CONCLUSIONS: The decisive factor of
      ES was initial stroke severity. ES per se was not related to mortality.
      Surprisingly, in survivors, ES predicted a better outcome. We explain this
      finding by a relatively larger ischemic penumbra in patients who have an ES after
      a stroke.

PMID- 9259752
TI  - Stroke prevalence in Taiwan. Findings from the 1994 National Health Interview
      Survey.
AB  - BACKGROUND AND PURPOSE: Stroke has been the second leading cause of death for all
      ages in Taiwan since 1983. However, despite the severity of the threat, stroke
      prevalence in Taiwan has not yet been addressed in a nationwide survey. In this
      study, the stroke prevalence in Taiwan was investigated using data from the 1994
      National Health Interview Survey. METHODS: This nationwide survey sought to
      obtain a nationally representative sample of households in Taiwan by using three
      stage stratified random sampling with a probability proportional to size. In the
      first stage, 58 townships were selected, from the 359 townships in Taiwan,
      according to their administrative structure and level of socioeconomic
      development. In the second stage, 149 basic administrative regions (tsun or li)
      were selected from the selected 58 townships. Finally, 3814 households were
      selected from the 149 selected tsuns or lis. Field interviews were carried out
      between October 1994 and December 1994. Follow-up interviews with families of
      stroke patients were made 2 years later. RESULTS: Of the selected households
      3119, or 81.8%, responded. A total of 11925 persons were interviewed, and 71 of
      them were stroke patients, with a crude point prevalence rate of 5.95 per 1000.
      The stroke prevalence increased steadily with age, from 0.51 per 1000 in persons
      aged 35 to 44 years to 113.6 per 1000 in persons aged 85 years or over. There was
      a weak association with higher stroke prevalence for persons living in eastern
      Taiwan or those of lower educational level. The overall male/female prevalence
      ratio was 1.17. The results of follow-up interviews showed a cumulative mortality
      rate of 25.4% within the 2-year period and an ischemic/hemorrhagic stroke ratio
      of 1.33 in 35 patients whose stroke type could be validated. CONCLUSIONS: Age was
      the most important factor correlating to stroke prevalence. On the basis of this
      result, planning policies and programs for stroke prevention in Taiwan should
      give a higher priority to (1) aggressive primary prevention for aged people who
      are apparently at higher risk of stroke and (2) early reduction of stroke risk
      factors in younger aged people whose immediate risk of stroke is lower but would
      increase significantly with age.

PMID- 9259754
TI  - Predictive factors of early seizures after acute cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Seizures within the first 48 hours of a first stroke or
      transient ischemic attack (TIA) are an independent prognostic factor for in
      hospital mortality. The aim of this study was to determine predictive factors of
      early seizures in first-ever stroke patients. METHODS: Data of 1220 first-ever
      stroke patients admitted consecutively to an acute stroke unit of a 450-bed
      teaching hospital between January 1986 and December 1993 were collected from a
      stroke registry. Demographic, anamnestic, clinical, neurological, and
      neuroimaging variables in the seizure and nonseizure group were compared using
      the t test and the chi 2 test. The independent predictive value of each variable
      on the development of early seizures was assessed with a logistic regression
      analysis. RESULTS: Early epileptic seizures were diagnosed in 29 patients (2.4%).
      Seizures were significantly more frequent in patients with hemorrhagic stroke
      (4.3%) than in those with ischemic stroke (2%). Patients with seizures were
      significantly younger and significantly more likely to have acute confusional
      state, cortical involvement, large stroke, and involvement of the parietal,
      frontal, occipital, and temporal lobes than patients without seizures. The in
      hospital mortality rate was 37.9% in the seizure group and 14.4% in the
      nonseizure group (P < .0005). After multivariate analysis, only cortical
      involvement (odds ratio of 6.01) and acute agitated confusional state (odds ratio
      of 4.44) were independent clinical factors for developing epileptic seizures.
      CONCLUSIONS: Cortical involvement in the neuroimaging studies and agitated acute
      confusional state at the onset of stroke were independent predictive factors of
      early seizures in first-ever stroke patients. The efficacy of anticonvulsant
      drugs in the prophylactic control of seizures should be assessed in prospective,
      randomized, double-blind clinical trials conducted in the subgroup of patients
      with the highest risk of developing epileptic seizures.

PMID- 9259755
TI  - MRA flow quantification in patients with a symptomatic internal carotid artery
      occlusion. The Dutch EC-IC Bypass Study Group.
AB  - BACKGROUND AND PURPOSE: Flow measurements in the collateral arteries of patients
      with internal carotid artery (ICA) occlusions may be important to estimate the
      risk of future stroke. Quantitative flow measurements in cerebropetal vessels can
      be reliably assessed by means of magnetic resonance angiography (MRA). METHODS:
      Fifty-four patients with transient or minor ischemic neurological deficits and an
      angiographically proven ICA occlusion and 16 control subjects underwent two
      dimensional phase-contrast MRA quantitative flow measurements through the common
      carotid arteries, basilar artery, ICAs, and middle cerebral arteries (MCA).
      RESULTS: Patients with a unilateral ICA occlusion and a 0% to 69% stenosis of the
      contralateral ICA had increased flow in the contralateral ICA (P < .005) and in
      the basilar artery (P < .005) compared with control subjects. Even patients with
      a 70% to 99% stenosis contralateral to the ICA occlusion had increased flow in
      the ICA (P < .05) as well as increased flow in the basilar artery (P < .001).
      Total cerebropetal flow was not significantly different between these patients
      and control subjects. Patients with bilateral ICA occlusions had an increased
      flow in the basilar artery (P < .001), while the total cerebropetal flow was less
      than in control subjects (P < .001). In all patients, flow was decreased in the
      ipsilateral MCA (P < .001) and in the contralateral MCA (P < .05). CONCLUSIONS:
      The contralateral ICA is the main supplying artery in patients with an ICA
      occlusion. Total cerebropetal flow decreases only when both ICAs are occluded. In
      patients with symptomatic ICA occlusions, an open contralateral ICA is probably
      important to retain the cerebral blood flow within normal limits.

PMID- 9259756
TI  - Comparison of transcranial color-coded sonography and magnetic resonance
      angiography in acute stroke.
AB  - BACKGROUND AND PURPOSE: We sought to compare the ability of transcranial color
      coded Doppler sonography (TCCS) and magnetic resonance angiography (MRA) to
      identify circulatory changes that occur after acute stroke. METHODS: Forty-four
      patients with a clinical diagnosis of acute stroke were studied with both TCCS
      and MRA within 24 hours of stroke onset. The appearances of all vessels
      identified on MRA were divided into three categories: normal, attenuated, and
      absent vessels. The basal cerebral arteries were identified with the use of TCCS,
      and their velocities were measured with pulsed-wave Doppler. The side-to-side
      asymmetry was calculated and expressed as an asymmetry index. RESULTS: Five
      patients could not be studied with TCCS because of lack of a suitable acoustic
      window. An additional 4 patients were too restless to tolerate MRA scanning.
      Three patients had intracerebral hemorrhages, 2 patients had intracerebral
      gliomas, and the remaining 30 patients had cerebral infarctions. In the group of
      patients with acute cerebral infarction, TCCS identified 10 patients with normal
      asymmetry indices, 1 patient with an increased asymmetry index, 9 patients with
      decreased asymmetry indices, and 10 patients with occlusion of the symptomatic
      middle cerebral artery (MCA). MRA identified 8 normal angiograms, 6 patients had
      attenuated MCA branch vessels, 4 patients had MCA branch occlusions, 2 angiograms
      demonstrated MCA main stem attenuation, and 10 angiograms showed MCA occlusion.
      CONCLUSIONS: TCCS and MRA are both noninvasive techniques that can be used to
      study the acute stroke patient. They both yield information regarding the
      pathophysiology of acute stroke and may be useful techniques in deciding on
      therapeutic interventions. The findings agree closely with each other, and these
      techniques may be useful in the long-term follow-up of stroke patients.

PMID- 9259757
TI  - Venous microembolic signals detected in patients with cerebral sinus thrombosis.
AB  - BACKGROUND AND PURPOSE: We sought to assess the usefulness of the Doppler
      technique in the monitoring of microembolic signals in the main venous outflow
      pathways in superior sagittal sinus thrombosis. METHODS: Transcranial Doppler
      ultrasound was performed with a range-gated 2-MHz transducer in 6 patients with
      superior sagittal sinus thrombosis, in 5 subjects with platelet
      hyperaggregability, and in 20 healthy volunteers. Emboli monitoring was performed
      mainly in one distal internal jugular vein for 10 to 15 minutes. RESULTS: Three
      of the six patients (50%) with superior sagittal sinus thrombosis had
      microemboli. None of the patients with platelet hyperaggregation or healthy
      volunteers revealed microemboli. CONCLUSIONS: Microemboli can be found in
      superior sagittal sinus thrombosis by Doppler ultrasound. Their prognostic
      significance remains to be determined.

PMID- 9259758
TI  - Harmonic imaging of the vertebrobasilar system.
AB  - BACKGROUND AND PURPOSE: Gas bubbles of ultrasound contrast agents resonate at
      frequencies used for diagnostic ultrasound and produce harmonics or multiples of
      the transmitted frequency. Processing of the second harmonic frequency results in
      a reduction of the signal-to-noise ratio and the signal-to-tissue artifacts. This
      study is the first to evaluate second harmonic imaging in the cerebral
      circulation. METHODS: We used a duplex system (HP SONOS 2500) in connection with
      a 1.8/3.6-MHz (second harmonic) and a 2.5-MHz (conventional) sector transducer.
      Levovist (6.5 mL; 400 mg/mL) was injected intravenously for second harmonic and
      conventional color duplex imaging in 13 healthy volunteers (age range, 23 to 34
      [median, 29] years). RESULTS: When second harmonic imaging was compared with
      conventional color duplex imaging, more cerebellar arteries were detected (35
      versus 31), the duration of blooming artifact was significantly reduced (7.9
      versus 29.9 seconds; P = .03), and the duration of diagnostically useful signal
      enhancement was increased (248.5 versus 117.4 seconds; P = .0003), but the
      maximal investigation depth was reduced (8.4 versus 9.3 cm; P = .001). When
      conventional and second harmonic duplex were compared, there was a significant (P
      < .04) difference in the systolic blood flow velocity in the vertebral and
      basilar arteries. CONCLUSIONS: Second harmonic color duplex imaging in the
      vertebrobasilar system increases the time of diagnostic useful signal enhancement
      and produces a better spatial resolution compared with conventional color duplex
      imaging.

PMID- 9259759
TI  - Variable agreement between visual rating scales for white matter hyperintensities
      on MRI. Comparison of 13 rating scales in a poststroke cohort.
AB  - BACKGROUND AND PURPOSE: Previous reports on the frequency, extent, and clinical
      correlates of white matter hyperintensities (WMHIs) have been contradictory. The
      purpose of this study was to test whether part of this variation could be
      explained by the different properties of the visual WMHI rating scales used.
      METHODS: The periventricular (PVHIs) and deep white matter (DWMHIs)
      hyperintensities of 395 poststroke patients were systematically analyzed and
      transformed to correspond to 13 different rating scales. The scales were compared
      with the use of Goodman-Kruskal measures of association. The relative
      frequencies, means, and medians of PVHI and DWMHI grades as well as Spearman rank
      correlations between WMHI grade and hypertension were calculated. RESULTS: At
      best more than 80% of the patients received an equivalent WMHI grade by different
      scales, but at worst the corresponding values were only 0.4% for PVHI and 18% for
      DWMHI. At best different scales categorized patients similarly in regard to WMHI
      grade, but at worst the corresponding values were 8% for PVHI and 57% for DWMHI
      ratings. The distribution of WMHI grades also varied, and when the effect of age
      on WMHI was assessed, some of the scales had a ceiling effect and some had a
      floor effect. Only 1 of the 7 PVHI, 5 of the 9 DWMHI, and 1 of the 3 combined
      rating scales showed a significant correlation with arterial hypertension, a
      putative risk factor for WMHIs. CONCLUSIONS: Some of the inconsistencies in
      previous studies of WMHIs are due to differences in visual rating scales. Our
      findings may warrant international debate regarding harmonization of WMHI
      ratings.

PMID- 9259760
TI  - Effects of the allosteric modification of hemoglobin on brain oxygen and infarct
      size in a feline model of stroke.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia and stroke are leading causes of
      morbidity and mortality. An approach to protecting the brain during ischemia is
      to try to increase the delivery of oxygen via the residual blood flow through and
      around ischemic tissue. To test this hypothesis, we used a novel oxygen delivery
      agent, RSR-13 (2-[4-[[(3,5-dimethylanilino)-carbonyl]-methyl]phenoxy]-2-methylpr
      opionic acid). Intravenous administration of RSR-13 increases oxygen delivery
      through allosteric modification of the hemoglobin molecule, resulting in a shift
      in the hemoglobin/oxygen dissociation curve in favour of oxygen delivery.
      METHODS: We studied RSR-13 in a feline model of permanent middle cerebral artery
      occlusion to assess its effects on cerebral oxygenation and infarct size. A
      randomized, blinded study of RSR-13 (n = 6) versus 0.45% saline (n = 12) was
      conducted, after an RSR-13 dose-escalation study (n = 4). Drug was administered
      as a preocclusion bolus followed by a continuous infusion for the duration of the
      experiment (5 hours). Brain oxygen was measured continuously with the use of a
      Clark oxygen electrode. Infarct size was measured at 5 hours after occlusion with
      computer-assisted volumetric analysis. RESULTS: The drug treatment group had
      consistently higher mean brain oxygen tension than controls (33 +/- 5 and 27 +/-
      6 mm Hg, respectively) and significantly smaller infarcts (21 +/- 9% versus 33 +/
      9%, respectively, P < .008). We observed an inverse relationship between the
      dose response of RSR-13 (the shift in the hemoglobin/oxygen dissociation curve)
      and infarct size. CONCLUSIONS: These results are evidence that allosteric
      hemoglobin modification is protective to the brain after acute focal ischemia,
      providing a new opportunity for neuroprotection and raising the possibility of
      enhancing the protective effect of thrombolysis and ion channel blockade.

PMID- 9259761
TI  - Three-dimensional analysis of vasospastic major cerebral arteries in rats with
      the corrosion cast technique.
AB  - BACKGROUND AND PURPOSE: Although mice, rats, and other small animals are commonly
      used for molecular biology research, their use in the evaluation of cerebral
      vasospasm after subarachnoid hemorrhage is somewhat problematic because of the
      correspondingly small size of their cerebral vessels. We have already reported
      that the corrosion cast technique was useful for evaluating newly formed cerebral
      vessels in neural grafts in these small animals. In the present study we applied
      the corrosion cast technique to the evaluation of hemolysate-induced cerebral
      vasospasm in rats and performed three-dimensional analysis for comparison. The
      casting was done 10 minutes after the hemolysate injection, so that only acute
      "vasospasm" was assessed. METHODS: After withdrawal of 0.1 mL cerebrospinal
      fluid, 0.2 mL hemolysate (n = 9) or saline (n = 10) was injected into the
      cisterna magna of male Sprague-Dawley rats weighing between 300 and 350 g. Ten
      minutes later, perfusion of a semipolymerized casting medium was performed at an
      injection pressure of 100 to 120 mm Hg. The brains were immersed and corroded in
      10% NaOH solution. After these procedures, the basilar artery as well as
      peripheral vessels was analyzed morphologically with scanning electron
      microscopy. Conventional histological analysis with the use of paraffin-embedded
      section with hematoxylin-eosin staining was also performed, and the results were
      compared with those for the corrosion cast methods. RESULTS: In the saline
      injected group, SEM showed that the inner surface of the basilar artery was
      smooth and the form of the endothelial cell was printed on the surface of the
      cast. In the hemolysate-injected group, the basilar artery showed an apparent
      vasospasm over its entire length, and corrugation was observed on the inner
      surface of the basilar artery in a three-dimensional fashion. Higher
      magnification revealed that the nuclei of the endothelial cells were distorted.
      Local narrowing of the basilar artery and vasospasm in the arteries of the
      anterior circulation and in peripheral arteries were also observed. Measurement
      of the inner diameter of the basilar artery showed 37.8% contraction in the
      hemolysate-injected group compared with the saline-injected group by the
      corrosion cast method. This degree of vasospasm was similar to that observed by
      the conventional histological method. CONCLUSIONS: In this report we show that
      detailed three-dimensional observation in the rat can be performed qualitatively
      and quantitatively with the corrosion cast technique. We conclude that this
      method derives an accurate measurement of the diameter of rat major cerebral
      arteries and is more reliable for analyzing vasospasm in rats than angiography
      and other conventional procedures.

PMID- 9259762
TI  - Geographic variation in stroke mortality in blacks and whites in the United
      States.
AB  - BACKGROUND AND PURPOSE: We sought to determine whether the "Stroke Belt" has
      continued to shift and to assess variation in geographic patterns by age, sex,
      and race. METHODS: Mortality data for Health Service Areas for 1988 to 1992 were
      used for analyses of geographic mortality patterns for stroke by race, sex, and
      age (50, 70, and 90 years). RESULTS: In 1988 to 1992, considerable geographic
      variation in stroke mortality was demonstrated for each sex/race group. In black
      and white women and men, previously described high mortality in the southeastern
      United States persisted. Mortality rates were generally higher in the South than
      in the North and in the East than in the West. Compared with data from 1962 to
      1988, there was a continuation of the previously described westward shift of high
      rate areas to the Mississippi River valley, a trend more marked at age 50 years
      than at 70 or 90 years. Although rates in the Pacific region were low overall, a
      surprising area of high rates was seen in southern California among women at all
      three ages examined. CONCLUSIONS: In whites, rapid declines in stroke mortality
      in the Southeast have left West South Central states with relatively high
      mortality rates; this trend may continue as younger cohorts age. However, rates
      in the Southeast also remain high, especially for blacks.

PMID- 9259763
TI  - An analysis of perioperative surgical mortality and morbidity in the asymptomatic
      carotid atherosclerosis study.

PMID- 9259764
TI  - Caution with praziquantel in neurocysticercosis.

PMID- 9259765
TI  - Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes.
AB  - Chronic treatment of mice with morphine affects the proliferation,
      differentiation, and function of immune cells. In the present study, we
      investigated the mechanism by which morphine inhibits phytohemagglutinin
      (PHA)/interleukin-1 (IL-1)-induced thymocyte proliferation. When compared to
      control cultures, morphine-treated thymocytes showed decreased steady-state
      levels of bioactive IL-2 and IL-2 mRNA. The reduced IL-2 concentration and
      reduced transcript levels correlated well with a decreased rate of synthesis of
      IL-2 mRNA as determined by nuclear runoff assays. Subsequent studies showed that
      morphine treatment affected transcriptional control elements of the IL-2 promoter
      by inhibiting the synthesis of a specific trans-activating nuclear factor, c-Fos.
      c-Fos mRNA levels measured by semiquantitative RT-PCR were significantly
      decreased in thymocytes following treatment with morphine and activation with PHA
      and IL-1. Under identical conditions, c-Jun mRNA levels were not altered.
      Electrophoretic mobility shift studies with the AP-1 consensus oligonucleotide
      showed significantly decreased levels of AP-1-protein complex formation in
      nuclear extracts prepared from morphine-treated cells. These studies demonstrate
      for the first time that opioid alkaloids such as morphine can impair mitogen
      lymphokine-activated thymocyte proliferation by interfering with transcriptional
      activation of the IL-2 gene.

PMID- 9259766
TI  - Increased class Ib antigen display on TAP-2 mutant cells by a mitochondrial
      function inhibitor.
AB  - Class I histocompatibility antigen display is defective in the RMA-S mutant cell
      line due to a mutation in the Tap-2 gene, which encodes a peptide transporter.
      Incubation of RMA-S cells with oligomycin, an inhibitor of mitochondrial ATPase,
      strongly increased lysis by cytotoxic T lymphocytes (CTL) specific for the class
      Ib antigen H2-M3, and lysis by Qa-1b-specific CTL was restored. Oligomycin did
      not affect normal class I display on RMA cells. Treatment of RMA-S cells with
      other inhibitors of mitochondrial function failed to increase lysis by anti-H2-M3
      or Qa-1b CTL. Lysis by allogenic CTL specific for H-2b antigens was either not
      enhanced or only weakly increased, depending upon the H-2 haplotype of the
      alloreactive effector cells used.

PMID- 9259767
TI  - Similar ligand densities required for restimulation and effector function of
      cytotoxic T cells.
AB  - This study compared ligand densities on antigen-presenting cells (APCs) needed
      for in vitro restimulation of in vivo primed T cells and for in vitro assessed T
      cell effector function. Spleen cells of lymphocytic choriomeningitis virus (LCMV)
      primed mice were restimulated in vitro with graded amounts of virus-derived
      peptides using macrophages or a cloned dendritic cell line as APCs. To test for
      effector function of these cytotoxic T cells, the same APCs pulsed with graded
      amounts of the peptides were used as target cells in an in vitro 51Cr release
      assay. The same peptide concentration that rendered an APC restimulatory for
      primed cytotoxic T lymphocytes (CTLs) also rendered it susceptible for lysis by
      the same CTLs. In addition, the same peptide concentrations that made macrophages
      susceptible for CTL-mediated lysis induced proliferative responses in vitro of in
      vivo primed memory CTLs. Thus, restimulation of in vivo primed T cells--measured
      by either proliferation or cytotoxic effector function--or sensibilization of
      target cells for lysis requires similar ligand densities on APCs and is
      therefore, contrary to expectations, governed by similar overall avidity
      thresholds. These results have implications for CTL memory.

PMID- 9259768
TI  - Activation of NK1.1+ T cells in vitro and their possible role in age-associated
      changes in inducible IL-4 production.
AB  - Interleukin (IL)-12 or IL-4 produced early in an immune response directs the
      differentiation of naive antigen-activated CD4+ T cells down a Th1 or Th2
      pathway. The NK1.1+ subset of T cells promptly produces IL-4 following activation
      in vivo. We demonstrate here that NK1.1+ T cells can be directly induced to
      produce IL-4 in vitro when activated under serum-free culture conditions.
      Platelet-derived growth factor in cell culture medium was inhibitory to the
      production of IL-4 by NK1.1+ T cells in vitro. Lymphocytes obtained from
      secondary lymphoid organs of aged mice produced greater quantities of IL-4
      following stimulation than lymphocytes from mature adult animals. Aged mice
      expressed elevated percentages of NK1.1+ T cells in their secondary lymphoid
      organs and peripheral blood. While this cell type was responsible for the total
      early IL-4 produced by lymphocytes from mature adult mice, both NK1.1+ and memory
      phenotype (CD44high, CD45RBlow, NK1.1-) T cells from aged donors produced IL-4
      following polyclonal T cell activation.

PMID- 9259770
TI  - Cyclic AMP analogue as a triggering signal for the induction of nitric oxide
      synthesis in murine peritoneal macrophages.
AB  - To understand the role of cAMP during macrophage activation, we investigated the
      effects of various cAMP analogues in the induction of nitric oxide (NO) synthesis
      in murine peritoneal macrophages. Intracellular cAMP modulators such as N6,O2'
      dibutyryl cyclic AMP (DB-cAMP), 8-bromo-cAMP, or 8-chloro-cAMP had no effect on
      NO synthesis by themselves, whereas cAMP analogues in combination with interferon
      gamma (IFN-gamma) had a marked cooperative induction of NO synthesis in a dose
      dependent manner. This increase in NO synthesis was reflected as an increased
      amount of inducible NO synthase mRNA, as determined by Northern blotting. To find
      the point in the signaling pathways of macrophage activation at which cAMP is
      involved, we carried out several of the following experiments. Although DB-cAMP
      showed synergistic action with rIFN-gamma to induce NO synthesis when the cells
      were treated with DB-cAMP after or with simultaneous treatment with rIFN-gamma,
      there is no synergistic induction of NO synthesis when the cells were treated
      with DB-cAMP 6 hr before treatment with rIFN-gamma. In addition, when phorbol 12
      myristate 13-acetate (PMA), which is known to provide a triggering signal in the
      induction of NO synthesis in murine macrophages, was added to the cells 6 hr
      after the treatment with DB-cAMP, PMA showed no synergistic cooperation with DB
      cAMP. On the other hand, DB-cAMP alone induced the release of NO to the
      incubation medium from bacillus Calmette-Guerin-infected peritoneal macrophages
      just as lipopolysaccharide (LPS) did. However, DB-cAMP, unlike LPS, decreased the
      secretion of tumor necrosis factor-alpha from IFN-gamma-treated macrophages.
      Based on the results obtained in this study, we suggest that cAMP analogue could
      give a "triggering" signal which might be different from one given by LPS in the
      production of NO by primed macrophages.

PMID- 9259771
TI  - CD27/CD70 interaction contributes to the activation and the function of human
      autoreactive CD27+ regulatory T cells.
AB  - CD27, a tumor necrosis factor receptor family member, is a constimulatory
      molecule for T and B cell activation. We demonstrate here that CD27 signaling is
      critical for T cell activation in the autologous mixed lymphocyte reaction (aMLR)
      and for aMLR-induced generation of regulatory T cells that suppress pokeweed
      mitogen-driven immunoglobulin G synthesis by B cells. Moreover, CD27, expressed
      on CD45RA+ CD4+ T cells, is directly involved in the suppressor function of aMLR
      activated CD4+ T cells, probably by interfering with the interaction between
      CD70, the CD27 ligand, expressed on CD45RO+ CD4+ helper T cells, and CD27,
      expressed on B cells. CD8+ T cells, which are required in this system to obtain
      suppression, on the other hand, do not need CD27 engagement to exert their
      suppressor function.

PMID- 9259769
TI  - Phenotypic and immunohistological analyses of the human adult thymus: evidence
      for an active thymus during adult life.
AB  - We analyzed cellular content of thymic samples from 26 human healthy donors,
      ranging from 1 week postnatal to 49 years old. Our results showed that there was
      an overall decrease in cellular density, beginning early during life, but with
      two peaks of cellular density, at 9 months and 10 years of age. Histological and
      immunohistological analyses showed that variations in cellular density were
      correlated with the morphological changes observed during thymic involution,
      namely the enlargement of interlobular trabeculae and the development of
      adipocytic tissue. However, the adult thymus still contained thymocytes, up to 49
      years. Phenotypic analysis showed no significant variations according to the age
      of donors in the distribution of the main thymocyte subsets, both precursors and
      more mature cells. These results suggest that the human thymus remains active
      during adult life.

PMID- 9259772
TI  - Acquired resistance to experimental autoimmune encephalomyelitis is independent
      of V beta usage.
AB  - In Lewis rats, activated encephalitogenic T-helper cells elicit a single bout of
      experimental autoimmune encephalomyelitis (EAE). Recovery from EAE is marked by
      reduced susceptibility to disease reinduction. The purpose of this study was to
      determine whether a dominant expression of V beta gene segments by
      encephalitogenic T cells was required for development of recovery-associated
      resistance. Several polyclonal and monoclonal T cell lines were derived from
      Lewis rats sensitized with R72-86, a synthetic peptide representing the 72- to 86
      amino-acid sequence of rat myelin basic protein (RMBP). The results revealed
      broad heterogeneity among encephalitogenic T cells specific for R72-86 in regard
      to V beta expression and CDR3 sequence. Encephalitogenic clones exclusively
      bearing either V beta 4 or V beta 10 TCR or polyclonal T cells bearing
      heterogeneous TCR transferred EAE to recipient rats and elicited resistance to
      EAE as revealed by subsequent challenge with guinea pig (GP)MBP in complete
      Freund's adjuvant (CFA). Nonpathogenic V beta 3+ and V beta 8.6+ clones specific
      for the 68-86 and 55-66 regions of MBP, respectively, did not elicit effective
      protection from EAE. These data indicate that induction of postrecovery
      resistance to EAE does not depend upon a particular V beta usage.

PMID- 9259773
TI  - IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor
      bearing mice and enhances adoptive immunotherapy: the potential role of NK cell
      subpopulations.
AB  - The daily administration of IL-15 to cyclophosphamide (CY)-injected mice bearing
      the 76-9 rhabdomyosarcoma was shown to prolong the period of remission induced by
      CY. In addition, IL-15 was shown to enhance the efficacy of adoptive
      immunotherapy. Cytotoxicity assays using spleens from normal and tumor-bearing
      mice indicated that IL-15 enhanced NK cell activity but there was no evidence for
      class I-restricted cytolytic T cell activity. To determine whether IL-15 was
      likely to induce different cytotoxic effectors at the tumor site compared with
      the spleen, tumors were removed after CY injection and cell suspensions were
      incubated with IL-15 in parallel with isolated spleen cells. Both populations
      were seen to expand to yield predominantly cells coexpressing NK1.1 and B220
      antigens. However, tumor-associated NK cells were shown to differ from expanded
      spleen NK cells in terms of the proportions of LGL-1+ cells and cells expressing
      early and late NK cell differentiation antigens. Both expanded populations
      expressed high NK cell cytotoxic activity but only the spleen cells expressed
      lymphocyte-activated killer cell activity. It was apparent that the expanded
      tumor-associated NK cells expressed low-level class I-restricted lytic activity.
      The potential of activated NK cells in the circulation to exert anti-tumor
      effects was shown by the adoptive transfer of expanded NK cells to tumor-bearing
      mice after CY injection when significant prolongation of life was seen in all
      cases. The data indicate that IL-15 may serve as a useful anti-cancer adjuvant by
      activating initially the NK cell arm of the immune network.

PMID- 9259774
TI  - High concentrations of antigenic ligand activate and do not tolerize naive CD4 T
      cells in the absence of CD28/B7 costimulation.
AB  - We evaluated whether signals transmitted through the T cell receptor (TCR) can
      activate naive CD4 T cells expressing a transgenic TCR specific for a defined
      peptide/MHC ligand in the absence of CD28/B7 costimulation. Our results showed
      that CD28/B7 costimulation was required at low, but not at high, concentrations
      of antigenic ligand. This was the case whether the CD28/B7 costimulatory pathway
      was blocked by CTLA-4 Ig fusion protein or by the chemical fixation of antigen
      presenting cells. Naive CD4 cells stimulated with high concentrations of antigen
      and without CD28 costimulation produced low but detectable amounts of IL-2 and
      interferon-gamma. Furthermore, naive CD4 T cells activated for a 7-day period by
      either low or high concentrations of antigen with or without CD28 costimulation
      were functionally similar, indicating that signals transmitted through the TCR
      were not intrinsically tolerogenic for CD4 T cells.

PMID- 9259775
TI  - Immunotherapeutic potential of tumor antigen-pulsed and unpulsed dendritic cells
      generated from murine bone marrow.
AB  - Dendritic cells (DC) are highly efficient antigen-presenting cells able to
      capture, process, and present antigens to naive and primed T-cells. In this
      study, we have investigated the ability of DC, derived from murine bone marrow
      and pulsed with tumor cell extracts, to induce regression of preexisting tumors.
      In an experimental model of B16 melanoma in B6 mice, a significant reduction in
      metastatic nodules in the lungs was observed in tumor-bearing animals treated
      with either DC alone or DC pulsed with tumor extracts. Kinetic studies
      demonstrate that the efficacy of these tumor vaccines is inversely related to
      tumor burden. In this model, tumor-specific cytotoxic T-cells (CTL) could also be
      induced in vitro from spleen cells derived from tumor-bearing animals treated
      with DC pulsed with tumor extracts. Untreated mice had no CTL. Furthermore, DC
      alone elicited tumor-specific CTL responses in tumor-bearing mice, but not in
      naive mice. Immune cell depletion experiments show that the therapeutic effects
      of DC are primarily mediated by CD8+ T-cells, while CD4+ T-cells and NK cells are
      involved in DC-mediated antitumor immunity to a limited extent. These results
      illustrate the potential use of DC and DC pulsed with tumor extracts as potent
      therapeutic reagents for cancer and provide a rationale for using DC in vivo to
      eliminate disseminated tumors or residual tumor deposits following surgery.

PMID- 9259776
TI  - Influence of local environment on incorporation of ceramic for lumbar fusion.
      Comparison of laminar and intertransverse sites in a canine model.
AB  - OBJECTIVES: To evaluate bone growth into macroporous ceramic in a canine model in
      terms of the effect at the lumbar spine site (lamina versus transverse process
      site) and the depth of the area within the ceramic block (peripheral or central
      areas). SUMMARY OF BACKGROUND DATA: Previous comparative studies have assessed
      that the efficacy of bone graft substitutes for spine fusion depends on their
      physicochemical properties and on the mechanical environment, but rarely on the
      grafting site at the lumbar spine level. METHODS: Posterior and lateral
      arthrodesis using pedicular instrumentation was performed at L2, L3, and L4 with
      a parallelepipedic ceramic block in an experimental group of dogs. A second group
      of dogs was fused with only autogenous bone graft to compare the fusion stiffness
      obtained with this material with the stiffness obtained with ceramic. Dogs were
      studied for 9 months. A biomechanical test and histomorphometric analysis were
      conducted. RESULTS: With the biomechanical test, no significant differences were
      found between ceramic and autogenous bone. The percentage of newly formed bone
      was higher (P < 0.0001) at the lamina (26.52 +/- 6.45%) than at the transverse
      process site (17.33 +/- 2.54%). For both locations, the highest amount of newly
      formed bone was observed in the area of close contact between ceramic and bone,
      and the lowest was observed in central areas (24.6 +/- 5.9% for the laminar site,
      14.79 +/- 1.75% for the transverse process site). CONCLUSION: This animal study,
      which replicated the human procedure in posterolateral lumbar fusion, showed a
      significant difference of ceramic incorporation between laminar and
      intertransverse sites. This histomorphometric analysis also confirmed the
      relationship between bone in-growth and ceramic thickness and ceramic contact
      area with bone.

PMID- 9259777
TI  - Transforaminal and posterior decompressions of the lumbar spine. A comparative
      study of stability and intervertebral foramen area.
AB  - STUDY DESIGN: Ten fresh, cadaveric, two-vertebrae, functional spinal units were
      used to study the pathoanatomy, intervertebral foraminal area, and flexibility
      changes after posterior and transforaminal decompression. OBJECTIVES: To
      determine the feasibility of an endoscopic transforaminal approach as an
      alternative to conventional approaches, to establish the adequacy of
      transforaminal decompression without destabilizing the spine, and to study the
      structural changes in the spine after decompressions. SUMMARY OF THE BACKGROUND
      DATA: Posterior decompression entails major dissection and excision of bone and
      ligaments to access the spinal canal. Posterior decompression may be complicated
      by acute or chronic spinal instability, and the adequacy of lateral decompression
      is highly subjective. METHODS: The functional spinal units were mounted in quick
      setting epoxy blocks. Pre- and postoperative computed tomography scans were taken
      to study changes in the foraminal area. Pre- and postoperative flexibility and
      anatomic studies were performed to compare the results. RESULTS: A 45.5% increase
      in the intervertebral foraminal area was possible, there was no flexibility
      change, and minimal anatomic damage to the spine was noted after transforaminal
      decompression. A 34.2% increase in the intervertebral foraminal area and a
      significant increase in extension and axial rotation flexibility were noted after
      the posterior decompression. CONCLUSION: Transforaminal decompression produced a
      significantly larger increase in the intervertebral foraminal area than posterior
      decompression, without increasing the range of motion or neutral zone in any
      direction. Because there was no violation of the anatomic integrity of the spine
      in the transforaminal approach, the risk of surgically induced instability was
      minimized. Endoscopic transforaminal decompression is a feasible alternative to
      current approaches.

PMID- 9259778
TI  - Restoration of pedicle screw fixation with an in situ setting calcium phosphate
      cement.
AB  - STUDY DESIGN: Pedicle screws were pulled out of human cadaveric vertebrae before
      and after augmentation with polymethylmethacrylate or in situ-setting calcium
      phosphate cement. The fixation strength of screws augmented with calcium
      phosphate cement was compared with that of screws augmented with
      polymethylmethacrylate. OBJECTIVES: To determine whether a new in situ-setting
      calcium phosphate cement might be suitable for augmenting the fixation of pedicle
      screws. The principle objective was to compare the pull-out resistance of screws
      augmented with calcium phosphate cement with the pull-out behavior of screws
      augmented with polymethylmethacrylate. Polymethylmethacrylate augmentation was
      chosen as the standard because of its current clinical use. Five types of screws
      were tested to determine whether screw design had an effect on the efficacy of
      augmentation. SUMMARY OF BACKGROUND DATA: Although many factors affect the pull
      out resistance of pedicle screws, a key determinant of their performance is the
      strength of their attachment to the spine. In elderly, osteopenic patients, the
      screw-bone interface is especially at risk for stripping during insertion or pull
      out after surgery. In these patients, polymethylmethacrylate has been used to
      augment pedicle screw fixation, although its use is not without risk. In situ
      setting calcium phosphate cements may provide an alternative to
      polymethylmethacrylate in this application. Like polymethylmethacrylate, calcium
      phosphate cements can be injected into the prepared screw hole. They have the
      added advantage of being resorbed and replaced during healing and normal bone
      remodeling. METHODS: Thirty human lower lumbar vertebrae (L3-L5) were implanted
      bilaterally with one of five types of pedicle screws (n = 6 for each screw type).
      The screws were pulled out 3.0 mm at 0.25 mm/sec with a servohydraulic materials
      testing machine. The 3.0-mm pull-out distance, which was slightly longer than one
      thread pitch, was designed to strip the screw-bone interface but to leave the
      pedicle otherwise intact. After the initial testing, the screws in each vertebrae
      were removed, and the screw tracks were filled with 2.0 cc of
      polymethylmethacrylate (one side) or calcium phosphate cement (contralateral
      side). After augmentation, the screws were reinserted, and the cements were
      allowed to harden for 24 hours. Postaugmentation testing followed the protocols
      for preaugmentation testing, and the pull-out resistance of screws augmented with
      calcium phosphate cement was compared with the pull-out resistance of screws
      augmented with polymethylmethacrylate. RESULTS: Mechanically, calcium phosphate
      cement compared favorably with polymethylmethacrylate for augmenting pedicle
      screws. Both restored the strength of the screw-bone interface: across all screw
      types, the average increase in pull-out strength was 147% with
      polymethylmethacrylate augmentation and 102% with calcium phosphate cement. There
      were no significant differences because of screw type with either type of
      augmentation. CONCLUSIONS: The in situ-setting calcium phosphate cement
      investigated in this study compared favorably with polymethylmethacrylate in a
      single-cycle, pull-out test of augmented pedicle screws in senile trabecular
      bone. With further evaluation, this cement may offer an alternative to
      polymethylmethacrylate for the enhancement of pedicle screw fixation clinically.

PMID- 9259779
TI  - Radiographic classification of Os odontoideum and its clinical significance.
AB  - STUDY DESIGN: This study analyzed the relationship between the configuration of
      the atlantoaxial joint and the clinical characteristics of patients with os
      odontoideum. OBJECTIVES: To compare three types of atlantoaxial configurations of
      os odontoideum from the viewpoint of clinical characteristics. METHODS: Twelve
      patients were classified into the following three types according to their
      atlantoaxial configuration on an anteroposterior radiogram: round (n = 6), cone
      (n = 4), and blunt-tooth (n = 2). Clinical features in each group were compared
      in terms of mean age, gender distribution, severity and type of myelopathy, and
      degenerative findings of the atlantoaxial joint. RESULTS: The patients in the
      round type group were predominantly women and had more severe myelopathy than
      that of patients in the other groups. According to Crandall's classification of
      myelopathy, all patients showed the transverse lesion syndrome in the cone and
      blunt-tooth types. Four of six patients with the round type of atlantoaxial
      configuration had the Brown-Sequard syndrome. With the round type, it appeared
      that the lateral mass of the axis tended to dislocate laterally, and this lateral
      instability associated with anteroposterior instability was believed to induced
      the Brown-Sequard syndrome. CONCLUSIONS: Myelopathy in patients in the round type
      group was the most severe compared with that of patients in the other three
      groups. This classification is considered useful for estimating clinical findings
      in os odontoideum.

PMID- 9259780
TI  - The effect of post-injury spinal position on canal occlusion in a cervical spine
      burst fracture model.
AB  - STUDY DESIGN: The canal space of burst-fractured, human cervical spine specimens
      was monitored to determine the extent to which spinal position affected post
      injury occlusion. OBJECTIVE: To test the null hypothesis that there is no
      difference in spinal canal occlusion as a function of spinal positioning for a
      burst-fractured cervical spine model. SUMMARY OF BACKGROUND DATA: Although
      previous studies have documented the effect of spinal positioning on canal
      geometry in intact cadaver spines, to the authors' knowledge, none has examined
      this relationship specifically in a burst fracture model. METHODS: Eight human
      cervical spine specimens (levels C1 to T3) were fractured by axial impact, and
      the resulting burst injuries were documented using post-injury radiographs and
      computed tomography scans. Canal occlusion was measured using a custom transducer
      in which water was circulated through a section of flexible tygon tubing that was
      passed through the spinal canal. Any impingement on the tubing produced a rise in
      fluid pressure that was monitored with a pressure transducer. Each spine was
      positioned in flexion, extension, lateral (and off-axis) bending, axial rotation,
      traction, and compression, while canal occlusion and angular position were
      monitored. Occlusion values for each position were compared with measurements
      taken with the spine in neutral position. RESULTS: Compared with neutral
      position, compression, extension, and extension combined with lateral bending
      significantly increased canal occlusion, whereas flexion decreased the extent of
      occlusion. In extension, the observed mechanism of occlusion was ligamentum
      flavum bulge caused by ligament laxity resulting from reduced vertebral body
      height. CONCLUSIONS: Increased compression of the spinal cord after injury may
      lead to more extensive neurologic loss. This study demonstrated that placing a
      burst-fractured cervical spine into either extension or compression significantly
      increased canal occlusion as compared with occlusion in a neutral position.

PMID- 9259781
TI  - Osteopenia in adolescent idiopathic scoliosis. A primary problem or secondary to
      the spinal deformity?
AB  - STUDY DESIGN: A cross-sectional study to assess the lumbar spinal and proximal
      femoral bone mineral density in girls aged 12, 13, or 14 years with adolescent
      idiopathic scoliosis and to compare them with bone mineral densities of an age
      matched control group. OBJECTIVES: To determine whether there is an association
      of osteopenia with idiopathic scoliosis, to compare bone mineral density in
      patients with scoliosis in different age groups with healthy controls, and to
      correlate bone mineral density with scoliotic parameters, including the pattern
      and magnitude of the curve. SUMMARY OF BACKGROUND DATA: Routine radiographs allow
      very limited assessment of osteopenia. Therefore, only a few studies have
      compared osteopenia in patients with scoliosis with that in healthy individuals.
      New techniques allow a more reliable quantification of the bone mineral state in
      adolescent idiopathic scoliosis. Available series in the literature either had a
      small sample population with inadequate controls or examined a large age range.
      METHODS: Using a dual energy x-ray absorptiometer, bone mineral density was
      measured in the predominant trabecular bone area, i.e., the lumbar spine (L2-L4)
      and bilateral proximal femur, in 81 girls aged 12, 13, or 14 years old with
      idiopathic scoliosis of various degrees of severity. Results were compared with
      those of 220 age-matched healthy control girls. RESULTS: In all three age groups,
      scoliotic patients had significantly lower bone mineral density in all measured
      regions than that in the control individuals (student's t test). Sixty-eight
      percent of the scoliotic individuals had a significantly reduced bone mineral
      density. Differences in bone mineral density between bilateral hips (paired t
      test) were not statistically significant either in scoliotic patients or in
      healthy control individuals. No differences in body weight, body height, or
      menarche status were found between the scoliotic and control individuals.
      Correlation studies showed that, in scoliotic patients, the values of bone
      mineral density did not correlate with the curve degree or curve pattern.
      CONCLUSIONS: There is a persistently lower bone mineral density in patients
      between 12 years and 14 years of age with idiopathic scoliosis. The decreased
      bone mineral density occurred in patients with idiopathic scoliosis before the
      age of 12 years, with no further progression from the age 12 to age 14, and did
      not correlate with the scoliosis degree or pattern. These findings suggest that
      the osteopenia in idiopathic scoliosis may be related to the primary etiology of
      the disease rather than secondary to the asymmetrical mechanical forces
      associated with the back deformities.

PMID- 9259782
TI  - Iliosacral screw fixation for pelvic obliquity in neuromuscular scoliosis. A long
      term follow-up study.
AB  - STUDY DESIGN: This was a retrospective review of a consecutive series of patients
      with neuromuscular spinal deformity who underwent posterior fusion and pelvic
      fixation using a long construct and an iliosacral screw. OBJECTIVES: To evaluate
      the risks and benefits of iliosacral screw fixation. SUMMARY OF BACKGROUND DATA:
      Neuromuscular scoliosis with pelvic obliquity poses one of the most challenging
      instrumentation problems, mainly because of the poor bone quality frequently
      found within the sacrum. Complications include failure of instrumentation, loss
      of sacral fixation, loss of lumbar lordosis, and a high rate of nonunion.
      METHODS: One hundred fifty-four patients with neuromuscular scoliosis and pelvic
      obliquity underwent posterior arthrodesis with pelvic fixation using an
      iliosacral screw. Anteroposterior scoliosis Cobb angle, frontal pelvic obliquity,
      and sacral inclination angle were measured before surgery, immediately after
      surgery, and at the 5-year and 3-month follow-up examination. Influence of
      etiology, severity of deformity, and associated anterior release at the scoliotic
      curve above also were assessed. RESULTS: Correction of scoliosis Cobb angle
      ranged from 53% to 70%, and loss of correction ranged from 3% to 14% at the last
      follow-up examination. Correction of pelvic obliquity ranged from 60% to 84%, and
      loss of correction was mild. Sacral inclination angle approached normal values in
      all patients, except for those with myelomeningocele who had preoperative pelvic
      retroversion. Loss of correction ranged from 0.3 degree to 5.4 degrees at the
      last follow-up examination. Complications and loss of correction mostly were
      encountered in patients with myelomeningocele and spinal muscular atrophy.
      CONCLUSIONS: Iliosacral screw fixation in neuromuscular scoliosis is technically
      standardized and easy and offers mechanically efficient and stable fixation.

PMID- 9259783
TI  - Calcification of lumbar ligamentum flavum and facet joints capsule.
AB  - STUDY DESIGN: The incidence of calcification in ligamentum flavum and posterior
      capsule demonstrated by computed tomography was reviewed in a series of 147
      patients in whom 419 lumbar levels were studied. OBJECTIVES: To find a
      relationship between mechanical lumbar pathology and the calcification of the
      ligamentum flavum and posterior capsule. SUMMARY OF BACKGROUND DATA:
      Calcification of the ligamentum flavum and posterior capsule has been found in
      diffuse idiopathic skeletal hyperostosis and in metabolic disorders. Although
      this fact is considered a manifestation of degenerative disease of the spine, it
      barely has been studied, and many questions remain unresolved. METHODS:
      Calcifications were classified according to location as follows: 1) ligamentum
      flavum: upper attachment, lateral or capsular extension, caudal attachment,
      interlaminar portion or 2) posterior capsule. RESULTS: The following statistical
      associations were found: 1) degenerative facet joint disease with posterior
      capsule and lateral or capsular extension calcifications, 2) lumbarized vertebra
      with lateral or capsular extension and upper attachment calcifications, and 3)
      isthmic spondylolisthesis with lateral or capsular extension calcification.

PMID- 9259784
TI  - Groin pain associated with lower lumbar disc herniation.
AB  - STUDY DESIGN: Retrospective clinical and magnetic resonance imaging study of
      patients with groin pain associated with lower lumbar disc herniation.
      OBJECTIVES: To demonstrate the clinical features and magnetic resonance imaging
      findings of these patients. SUMMARY OF BACKGROUND DATA: Patients with lumbar disc
      herniation sometimes report groin pain. Little mention has been made, however,
      regarding the clinical features of groin pain stemmed from lower lumbar disc
      herniation until now, with only Murphey referring to groin pain in disc disease.
      METHODS: A total of 512 patients were diagnosed with singular lower lumbar disc
      herniation (L4-L5 and L5-S1) at Kakegawa City General Hospital between July 1990
      and December 1993. Of these patients, 21 (4.1%) reported groin pain. The
      characteristic clinical features and magnetic resonance imaging findings of the
      21 patients were investigated and compared with the features and findings of
      patients with no groin pain. RESULTS: Patients with groin pain had a higher mean
      age and lower rate of low back pain, and L4-L5 discs were more likely to be
      involved than L5-S1 discs. In their magnetic resonance images, herniation tended
      to be more central than in patients with no groin pain. CONCLUSIONS: Elderly
      patients with L4-L5 protruding herniation of the anulus fibrosus were most likely
      to experience groin pain. The sinuvertebral nerve that innervates the posterior
      anulus fibrosus, the posterior longitudinal ligament, and the dura was indicated
      as the afferent nerve of groin pain.

PMID- 9259785
TI  - Spondylodiscitis. Clinical and magnetic resonance diagnosis.
AB  - STUDY DESIGN: This study reviews 65 patients with spondylodiscitis, both
      spontaneous and postoperative and of different etiology, studied by magnetic
      resonance imaging. OBJECTIVES: To define the magnetic resonance imaging
      characteristics of infections of the spine in acute and chronic stages and to
      evaluate the role of magnetic resonance imaging in defining their etiology.
      BACKGROUND DATA: Early diagnosis of spondylodiscitis is often difficult because
      of the long latent period. Radiographs of the spine, bone scan, and computed
      tomography scan provide insufficient data. METHODS: Among 65 patients with
      spondylodiscitis studied by magnetic resonance imaging, 24 were examined in the
      acute stage (clinical evolution between 7 days and 20 days), and 41 were examined
      in the chronic stage (3-6 weeks). The etiologic agent was staphylococcus in eight
      cases, Brucella in 13, Mycobacterium tuberculosis in 29, Salmonella in four, and
      unknown in 11. RESULTS: In cases observed in the acute stage, the disc and the
      vertebral bodies were hypointense in T1 and hyperintense in T2; this relatively
      constant finding was not correlated with the etiologic agent. In the chronic
      stage, cases caused by Brucella or of unknown etiology showed long T1 and T2
      relaxation times, with precocious contrast enhancement of the disc; in cases of
      tubercular etiology there was slight shortening of T1, with inhomogeneous
      enhancement of the involved vertebral bodies and late disc enhancement.
      CONCLUSIONS: Magnetic resonance imaging is the investigation method of choice in
      diagnosing spondylodiscitis, especially in very early stages of the disorder,
      when other investigations still yield negative results. In chronic stages,
      magnetic resonance imaging also allows tubercular spondylodiscitis to be
      distinguished from cases of different etiology.

PMID- 9259786
TI  - The epidemiology of low back pain in the rest of the world. A review of surveys
      in low- and middle-income countries.
AB  - STUDY DESIGN: A criteria-based review of the literature. SUMMARY OF BACKGROUND
      DATA: The literature on the epidemiology of low back pain is accumulating, but
      for the most part studies are restricted to high-income countries, which comprise
      less than 15% of the world's population. Little is known about the epidemiology
      of low back pain in the rest of the world. OBJECTIVES: To address the imbalance
      in the literature and to review the relatively few studies on the epidemiology of
      low back pain in low- and middle-income countries. Rates from these studies are
      contrasted with rates from selected high-income countries. In reviewing the
      literature, a hypothesis is tested: low back pain rates are higher in low-income
      countries than in high-income countries, not only because hard physical labor is
      more prevalent in low-income countries, but also because, unlike high-income
      countries, hard physical labor for older workers in low-income countries often is
      unavoidable. METHODS: Among other sources, articles for the review come from a
      search of the MEDLINE bibliographic database, with "back pain" and individual low
      and middle-income countries entered as key words. To avoid recall biases,
      findings specifically on point prevalence are reviewed. RESULTS: Within the
      categories of low-income and high-income countries, low back pain rates vary
      twofold or more. In comparisons between these categories of countries, rates on
      the whole are higher among the general populations of selected high-income
      countries than among rural low-income populations; specifically, rates are 2-4
      times higher among Swedish, German, and Belgium general populations than among
      Nigerian, southern Chinese, Indonesian, and Filipino farmers. Within low income
      countries, rates are higher among urban populations than among rural populations
      and still higher among workers in particular worksites, referred to as "enclosed
      workshops." CONCLUSIONS: The disparity in low back pain rates within categories
      of countries, high-income and low-income, calls attention to the high proportion
      of studies on the epidemiology of low back pain that are methodologically
      questionable. Recommendations are offered to improve the methodologic quality of
      this type of study. Conclusions may be drawn from comparisons between studies,
      although, in the absence of set methodologic standards, they are tentative. The
      considerably lower rates among populations of low-income farmers compared with
      rates of the affluent populations of selected northern European countries
      indicate that, contrary to the hypothesis proposed here, hard physical labor
      itself is not necessarily related to low back pain. The higher rates in urban low
      income populations as compared with rates in rural low-income populations and the
      sharply higher rates among workers in enclosed workshops of low-income countries
      suggest a disturbing trend: low back pain prevalence may be on the rise among
      vast numbers of workers as urbanization and rapid industrialization proceed.

PMID- 9259787
TI  - Sagittal back motion of college football athletes and nonathletes.
AB  - STUDY DESIGN: The study was designed as an ex post facto study using volunteers.
      OBJECTIVES: To compare sagittal back motion of male college athletes with that of
      nonathletes and to compare data from both groups with normative data. SUMMARY OF
      BACKGROUND DATA: Few studies have evaluated athletic demands on the spine. Much
      of the information on athletic demands comes from electromyographic studies,
      flexibility comparisons, and lift task studies. Although these studies provide a
      basis for back testing and evaluation, they do not present direct evidence of
      athletic low back performance. METHODS: Fifteen male college football athletes
      and 15 male college nonathletes volunteered for testing using the IsoStation B
      200 BSCAN 2.0 protocol (Isotechnologies, Inc., Hillsborough, NC). Measures were
      recorded for range of motion, isometric flexion and extension, and moderate and
      high dynamic flexion and extension. Data were analyzed using multivariate
      analysis of variance. RESULTS: The results of Hotelling's multivariate test were
      significant. Univariate follow-up analysis showed that athletes had significantly
      better isometric flexion, isometric extension, moderate dynamic flexion, high
      dynamic flexion, and high dynamic extension. Athletic data were compared with the
      BSCAN population data at the 50th and 80th percentile. Athletes were
      significantly better (P < 0.007) for all variables at the 50th percentile and for
      all dynamic variables at the 80th percentile. CONCLUSIONS: Within the limitations
      of the study, college football athletes had better sagittal back motion strength
      and speed as tested with the B-200 than nonathletes. Population data for the B
      200 were representative for nonathletes but nonrepresentative for football
      players.

PMID- 9259788
TI  - A study of functional spinal motion in women after instrumentation and fusion for
      deformity or trauma.
AB  - STUDY DESIGN: Photographs were used to measure the residual spine motion in 71
      women who had undergone spine fusion and instrumentation for spinal deformity or
      trauma. OBJECTIVES: To accurately define the ability of the patient to flex,
      extend, and bend to the right and left, thus providing the surgeon some accurate
      information rather than speculation regarding spinal motion. METHODS: The 71
      patients had undergone spine fusion with instrumentation for scoliosis, kyphosis,
      or spine trauma. The average age of the patient at surgery was 22 years, ranging
      from 11 years to 62 years. The average time since surgery was 6 years, ranging
      from 1 year to 32 years. Each patient had six views photographed: flexion,
      extension, right and left side bending from the front, and right and left side
      bending from the back. Each photograph was measured independently by two research
      assistants. A total of 852 photographs were analyzed. RESULTS: The average degree
      of right side bending was 22 degrees, that of left side bending was 23 degrees,
      that of flexion was 111 degrees, and that of extension was 30 degrees. For the 59
      patients who underwent fusion of seven levels or more and who were fused down to
      T12, L1, L2, L3, or L4, there was no correlation of the range of motion with the
      lowermost level of fusion, except in patients with fusion to L4 who had
      significantly less motion. Flexion was primarily a function of hamstring
      tightness and was best in those who exercised regularly (aerobics, gymnastics,
      ballet), regardless of the number of levels fused or the lowermost level of
      fusion. CONCLUSION: Typical spine fusions for deformity produce a moderate loss
      of functional motion, except in patients who undergo fusion to L4 who lose much
      more. The technique of analysis was found to be highly accurate and reproducible.

PMID- 9259789
TI  - Posterior surgical approach to the lumbar spine and its effect on the multifidus
      muscle.
AB  - STUDY DESIGN: This study investigated the changes in the lumbar muscles after
      posterior fusion of the lumbar spine and the potential correlation between
      muscular changes and the persistence of low back pain. OBJECTIVES: To evaluate
      prospectively the effect of the posterior approach to the spine on the lumbar
      erector spinae. SUMMARY OF BACKGROUND DATA: The posterior approach to the spine
      leads to considerable alteration of the erector spinae muscles. An eventual
      correlation between these changes and persisting pain or other clinical symptoms
      has not been investigated previously. METHODS: Seventy-five patients undergoing
      spondylosyndesis for different indications (43 patients) or a second operation
      for the removal of internal fixation (32 patients) were allotted to the study. In
      each patient, four biopsy specimens from the lumbar multifidus muscle were
      harvested; in 14 patients, biopsies were taken at both operations. Size and
      distribution of the fiber types (I, IIA, IIB, IIC) were determined, and pain
      scoring (visual analogue scale) and the presence of neurologic deficits were
      recorded. RESULTS: At the time of the first operation, 88% of the patients showed
      pathologic changes (altered internal structure, atrophy, type grouping) in one or
      more biopsies. Statistical analysis showed a correlation between both age and
      pain and type II (A + B) atrophy. After surgery, the patients showed
      significantly more biopsies with denervation signs than before surgery. No
      correlation could be made, however, between the intensity of pain before or after
      surgery and the relative number of biopsies with signs of denervation.
      CONCLUSIONS: Posterior surgery causes muscular alterations; however, no
      correlation with pain or other clinical symptoms could be established. Therefore,
      in the case of unsatisfactory results after surgery of the lumbar spine, reasons
      other than muscle damage caused by use of the posterior approach must be
      considered.

PMID- 9259790
TI  - A system for surgical staging and management of spine tumors. A clinical outcome
      study of giant cell tumors of the spine.
AB  - STUDY DESIGN: This study developed and independently applied a spine tumor
      classification system, referred to as the Weinstein-Boriani-Biagini system, in a
      retrospective analysis of a series of patients with spinal giant cell tumors from
      three institutions. OBJECTIVE: To evaluate factors of potential prognostic
      significance for recurrence of spinal giant cell tumors. SUMMARY OF BACKGROUND
      DATA: No prior reviews of patients treated with modern surgical techniques are
      available. METHODS: Charts and radiographs for 36 cases of spinal giant cell
      tumors were reviewed by an independent investigator. All patients had had recent
      clinical follow-up examinations. All patients were classified according to the
      Enneking system. A subgroup of 24 patients for whom preoperative computed
      tomography scans were available were classified using the Weinstein-Boriani
      Biagini staging system. Outcome measures included pain, neurologic status, and
      tumor recurrence. RESULTS: Recurrence rates were substantially higher among
      patients treated with attempted surgical excision before referral to a tertiary
      care center (83% vs. 18%). There was a higher recurrence rate for tumors that
      involved the vertebral body and posterior elements in comparison with lesions
      residing in only anterior elements (24% vs. 0%). Tumors that had extra-osseous
      extension into the canal and into the paraspinous musculature had a higher
      recurrence rate than tumors either confined to the osseous compartment or with
      extension either into the spinal canal or externally into paraspinous planes, but
      not both (21% vs. 10%). CONCLUSIONS: These results indicate that the Weinstein
      Boriani-Biagini system may prove useful in developing treatment algorithms and in
      assessing outcome for these rare and difficult lesions. At least in the case of
      giant cell tumors, the musculoskeletal tumor staging system as developed by
      Enneking for long bones suggests the ideal surgical margin and may provide
      information relevant to tumor recurrence rates. Additional aspects of tumor
      extent and location, however, may berelevant to primary tumor recurrence rates
      when the selesions occur in the spine.

PMID- 9259791
TI  - Super-acute aseptic spondylitis as the first manifestation of round calcifying
      nucleopathy in a 77-year-old man. A case report.
AB  - STUDY DESIGN: This is a report of an unusual case of very late onset,
      symptomatic, round calcifying nucleopathy. OBJECTIVE: To describe this unusual
      case of calcifying nucleopathy in a 77-year-old man who had no previous back
      problems, but had a history of diffuse skeletal hyperostosis. SUMMARY OF
      BACKGROUND DATA: The resorption of calcifying nucleopathy associated with
      reactional spondylitis is a classic occurrence in children but is rare in adults.
      METHODS AND RESULTS: Spondylitis was diagnosed on the basis of pain, a transient
      Babinski's sign, and systemic inflammation. Radiographs, a bone scan, and
      magnetic resonance imaging revealed a large calcified nucleopathy of the T12-L1
      disc associated with spondylitis of T12. The calcification disappeared within 3
      weeks, and recovery was clinically and biologically complete after treatment
      consisting of only rest and analgesics. CONCLUSION: A diagnosis of resorption of
      a round calcifying nucleopathy is not to be excluded in the elderly patient. This
      event can mimic an infectious spondylitis clinically and biologically.

PMID- 9259792
TI  - Hypertrophic spinal pachymeningitis. A case report.
AB  - STUDY DESIGN: This is a case report and review of the literature. OBJECTIVE: To
      describe the clinical findings and the surgical treatment of a 28-year-old man
      with hypertrophic spinal pachymeningitis in the thoracic and lumbar region
      managed by expansive laminoplasty. SUMMARY OF BACKGROUND DATA: Hypertrophic
      spinal pachymeningitis is extremely rare. No description of findings present
      after expansive laminoplasty for hypertrophic spinal pachymeningitis has been
      reported. METHODS: The clinical findings, course, and surgical treatment of a 28
      year-old man with a hypertrophic spinal pachymeningitis are presented. The
      patient required expansive laminoplasty. The follow-up period after the surgical
      procedure was 4.2 years. RESULTS: An unusual etiology of spinal cord compression
      by thickened dura mater was found with a contrast ring- or crescent-shaped
      enhancement on gadopentetate magnetic resonance imaging. Spasticity disappeared
      after the patient underwent expansive laminoplasty. CONCLUSION: This is the first
      report of a patient with hypertrophic spinal pachymeningitis treated with
      expansive laminoplasty. Spinal canal decompression and autogenous bone grafting
      are accepted treatments in the young patient. Careful observation of the patient
      to watch for local progression is necessary.

PMID- 9259793
TI  - Tuberculosis of the spine. Controversies and a new challenge.
AB  - Tuberculosis is a deadly disease affecting many people in the world. The
      prevalence of spinal tuberculosis is likely to rise as the numbers of those
      infected with human immunodeficiency virus rises. This presentation summarizes
      present knowledge of spinal tuberculosis and its management. It describes and
      updates material the author has previously published on this subject. The
      scientific basis for the clinical management of spinal tuberculosis has been well
      established by the British Medical Research Council group and Hong Kong surgeons.
      It is believed, however, that well-controlled basic and clinical studies are
      required if the incidence of the three unwanted complications of spinal
      tuberculosis is to be reduced further. Antituberculosis agents are the mainstay
      of management, with chemotherapy for 12 months preferred to shorter courses. The
      standard is a combination of isoniazid, rifampin, and pyrazinamide, with or
      without ethambutol. Anterior surgery consisting of radical focal debridement
      without fusion does not prevent vertebral collapse. The major advantage of
      anterior arthrodesis is the decreased tendency for progression of the deformity.
      Patients who present late with deformity are candidates for anterior debridement
      and stabilization with corrective instrumentation. Posterior stabilization with
      instrumentation has been found to help arrest the disease and to bring about
      early fusion. Posterior instrumented stabilization to prevent kyphosis in early
      spinal tuberculosis is indicated, however, only when anterior and posterior
      elements of the spine are involved, particularly in children. With early
      detection, institution of chemotherapy, and improved surgical techniques,
      patients with kyphosis rarely are seen today, particularly in urban centers that
      have an effective medical system. For these same reasons, patients with spinal
      tuberculosis who present with paraplegia and no deformity usually respond well to
      treatment. It is concluded that spinal tuberculosis without unsightly kyphosis
      and neurologic symptoms is a medical, rather than a surgical, condition. Surgery
      should be reserved for those patients who have advanced tuberculosis with
      unacceptable complications such as paraplegia and/or deformity.

PMID- 9259795
TI  - Social Security Bulletin. Annual statistical supplement, 1996.

PMID- 9259794
TI  - The epidemiology of low back pain in the rest of the world.

PMID- 9259796
TI  - Training horses--art or science?

PMID- 9259797
TI  - Exercise and the cardiovascular system.

PMID- 9259798
TI  - Biomechanics and the physiological costs of equine locomotion: a need for more
      research.

PMID- 9259799
TI  - The physiological basis of training the skeleton. The Sir Frederick Smith
      Memorial Lecture.
AB  - The skeleton consists of a series of elements with a variety of functions. In
      locations such as the skull, where shape or protection are of prime importance,
      the bone's architecture is achieved during growth under predominant genetic
      control. In locations such as the limbs, where the ability to withstand
      repetitive loading is important, only the general form of the bone will be
      achieved as a result of growth alone, the remaining characteristics resulting
      from an adaptive response to functional load bearing. In the horse, this
      functional load-bearing will be provided by the animal's natural activity pattern
      in box or paddock supplemented by the specific activities of the training
      regimen. It is the adaptive response to the total activity pattern that
      influences bone modelling and remodelling and so determines the bone's
      architecture. The objective of the training regimen is to ensure that this
      response achieves an appropriate match between bone architecture and the loads it
      is required to withstand during both training and athletic performance. We
      propose that for the match between architecture and load-bearing to be
      established, and maintained, subsequently, bone cells must be able to 'assess'
      directly or indirectly the functional strains produced within the bone tissue.
      Because these strains are used as feedback they are both the objective of
      functionally adaptive modelling and remodelling, and the stimulus for its
      control. The mechanisms whereby bone cells control skeletal modelling and
      remodelling to produce a functionally competent skeleton are unknown although
      some of the factors and sequence of events involved are presented here. The
      extent to which variation in training regimen affects bone architecture has not
      been studied systematically in any species.

PMID- 9259800
TI  - A comparative study of interval and conventional training in thoroughbred
      racehorses.
AB  - Eight horses with previous racing experience were used in a comparative study of
      training methods for Thoroughbred racehorses. They were randomly assigned to two
      groups of four horses each. One group was trained using an interval training
      method (IT) and the other using conventional training (CT) methods. Peak heart
      rates, heart rate recovery curves, peak plasma lactate levels, plasma lactate
      clearance rates and run times were used to evaluate differences in the training
      methods. Peak heart rates, heart rate recovery curves, and run times were not
      significantly different between the groups. However, higher lactate production
      and increased plasma lactate clearance by the IT group demonstrated an increased
      anaerobic capacity.

PMID- 9259801
TI  - Methodology and repeatability of a standardised treadmill exercise test for
      clinical evaluation of fitness in horses.
AB  - This paper describes the methodology necessary to perform a clinical exercise
      test and the expected variability in an individual horse's exercise test
      measurements based on comparing the results of two repetitions of the test with
      six horses. The exercise test measurements were obtained with an open flow
      respiratory gas analysis system, fast time response lactate analyser and an on
      board heart rate monitor during an incremental inclined treadmill exercise test.
      With the exception of peak venous lactate concentration (LACpeak), the results
      indicate that the mean variability in peak oxygen consumption (VO2peak) peak
      carbon dioxide production (VCO2peak), peak respiratory exchange ratio (Rpeak),
      peak heart rate (HRpeak), peak packed cell volume (PCVpeak), peak total plasma
      protein (TPPpeak) and the maximum number of steps completed during the exercise
      test (STEPmax) was less than 5 per cent. Variation in the regression analysis of
      VO2, VCO2 and HR versus velocity was also less than 5 per cent. Slightly higher
      variation was recorded for LAC and R. Mean variation in the regression analysis
      of PCV and TPP versus velocity was more than 16 per cent. Mean variation for all
      of the post exercise test measurements was less than 10 per cent at 1, 5 and 15
      mins post exercise. Therefore, the results obtained during a single exercise test
      are a reliable assessment of a horse's metabolic capability.

PMID- 9259802
TI  - Application of a standardised treadmill exercise test for clinical evaluation of
      fitness in 10 thoroughbred racehorses.
AB  - Clinical exercise stress testing is an important diagnostic tool for evaluating
      exercise intolerance and degree of fitness in human athletes. The purpose of this
      paper was to describe the methodology necessary to perform a clinical exercise
      test and report the results of performance evaluations on 10 Thoroughbred
      racehorses using this test. The test utilised an open flow gas analysis system
      for ease of use with untrained horses and a fast time response lactate analyser
      for rapid data analysis. Exercise test measurements used to evaluate fitness
      included peak oxygen consumption (mean VO2peak = 161.9 +/- 12.9 ml/kg/min), peak
      heart rate (mean HRpeak = 232 +/- 10 b/m), peak venous blood lactate
      concentration (mean LAC peak = 15.2 +/- 5.8 mmol/l), peak packed cell volume
      (mean PCV peak = 0.64 +/- 0.3 l/l) and the maximum number of steps completed
      (mean STEPmax = 8.7 +/- 0.5 steps). The relationship between these exercise test
      measurements with velocity and time post exercise was also evaluated. Change in
      serum creatine kinase levels resulting from exercise test were minimal (mean
      delta SCK = 72 +/- 53 u/l).

PMID- 9259803
TI  - Investigation of the vertical hoof force distribution in the equine forelimb with
      an instrumented horseboot.
AB  - A greater knowledge of the biomechanics is necessary in equine orthopaedics,
      therapeutics, farriery and for the selection of athletic horses. The purpose of
      this study was to determine the normal distribution of the vertical component of
      the hoof force using a measuring boot. The measurements were carried out using 20
      sound horses walking and trotting on a straight hard track. A force measuring
      horseshoe, attached to the foot with a boot, provided continuous recording of
      vertical forces at four locations on the hoof. For each measuring location, a
      computer program produced curves and calculated gait and force parameters. The
      position of the resultant force moved cranially during the stance phase. The
      vertical component was not distributed uniformly over the whole hoof surface.
      Thus the mechanical loading was greater in the caudal area than in the cranial
      area, especially after the foot impact on the ground. It was concluded that the
      heels and the quarters seemed to take a prominent part in dampening concussion
      and supporting bodyweight. More investigations are necessary to establish the
      relationships between the two functions and the frequent pathology of the caudal
      region of the foot.

PMID- 9259804
TI  - Kinetics of VO2 and VCO2 in the horse and comparison of five methods for
      determination of maximum oxygen uptake.
AB  - To determine whether maximum oxygen uptake (VO2max) in the horse in influenced by
      type of exercise test, five different protocols were evaluated in eight untrained
      Thoroughbreds exercised on a treadmill. With all protocols, horses were given a 5
      min warm-up on a 10 per cent treadmill slope. Three protocols were at a 10 per
      cent slope and included: 1) increasing the running speed by 1 to 2 m/sec every 60
      secs from 4 m/sec to a maximum of 12 m/sec; 2) running at 12 m/sec until fatigue;
      and 3) running for 3 to 4 mins at speeds ranging from 6 to 12 m/sec with rest
      pauses between exercise bouts. The fourth protocol employed a 24 per cent slope
      where animals exercised for 5 mins at 2 m/sec followed by 3 mins at 5 m/sec, and
      2 mins at 6 m/sec. The fifth test involved running at 11 m/sec while the slope of
      the surface was increased every 2 mins until the horses could not maintain the
      pace. A plateau in VO2 occurred in all protocols except when exercise was
      performed on a 24 per cent slope. Slow speed exercise at a steep grade (24 per
      cent) produced the highest VO2 (P < 0.05) even though there was no plateau in the
      VO2. A steady state for VO2 and VCO2 existed 90 secs after the onset of exercise
      with all protocols which involved 2 mins or more at each speed. The VO2 and VCO2
      values at all speeds of the rapid incremental exercise test were not different to
      those found at steady state in the third exercise protocol.

PMID- 9259805
TI  - The relationship between peak expiratory sound intensity and peak expiratory flow
      rate in the thoroughbred horse during exercise.
AB  - Peak expiratory sound intensity (dB SPL), obtained by means of a
      radiostethoscope, and peak expiratory flow rate, obtained using a mask
      incorporating a thermistor flow sensor, were measured in six Thoroughbreds over a
      range of stride rates from 100 to 140 strides per min. The results show linear
      relationships between peak dB SPL and stride rate, peak expiratory flow rate and
      stride rate and also between peak expiratory flow rate and peak dB SPL. Peak
      expiratory dB SPL can therefore indicate peak expiratory flow rate.

PMID- 9259806
TI  - Pulmonary artery, aortic and oesophageal pressure changes during high intensity
      treadmill exercise in the horse: a possible relation to exercise-induced
      pulmonary haemorrhage.
AB  - This study investigated changes in packed cell volume (PCV), pulmonary artery and
      aortic pressures, and the interaction between oesophageal pressure and pulmonary
      artery and aortic pressures during strenuous exercise in the horse. It was
      hypothesised that oesophageal pressure changes summate with pulmonary artery and
      aortic pressures during exercise and contribute to exercise-induced pulmonary
      haemorrhage (EIPH). Acute treadmill exercise (10 m/sec, 3 degrees incline)
      produced increases in heart rate (HR) from 50 to 202 beats/min; mean pulmonary
      artery pressure (PAP) from 28 to 80 mmHg; mean aortic pressure (AP) from 108 to
      157 mmHg; and PCV from 0.35 to 0.52 litres/litre. EIPH was observed in three of
      seven horses after treadmill exercise, but no differences in the above variables
      were observed between the two groups of horses. Electronic subtraction of the
      oesophageal pressure signal from PAP and AP signals indicated peak transmural
      pressures of approximately 150 mmHg pulmonary and 175 mmHg aortic pressure. The
      elevated PAP associated with exercise appeared related more to increased HR and
      less to PCV (blood viscosity) or AP (bronchial). Both pulmonary artery and aortic
      peak transmural vascular pressures were substantially influenced by oesophageal
      pressure changes; peak and mean pulmonary artery and aortic pressures were
      significantly higher than resting pressures, and may conceivably contribute to
      EIPH.

PMID- 9259807
TI  - Accuracy of formulae for calculating left ventricular volumes of the equine
      heart.
AB  - Echocardiography may be an accurate method of measuring left ventricular (LV)
      volumes and mass of the horse's heart. If so, studies of the heart size and
      hypertrophy would be possible. This study evaluated geometric models of the
      external and internal LV shapes, to determine which could be applied to
      echocardiographic measurements. We preserved 30 horses' hearts and measured their
      dimensions and cross sectional areas. These measurements were entered into seven
      formulae representing different geometric models of the ventricle and its
      chamber. We derived a correction factor to estimate the long axis as a fixed
      proportion of the external diameter, so that volumes could be determined from an
      M-mode or a cross sectional echocardiogram. Statistical analysis of the
      regressions of known volumes against calculated volumes measured by water
      displacement, demonstrated that the ellipsoid formula using cross sectional areas
      was very accurate in representing the external shape of the left ventricle (slope
      = 1.01 r2 = 96.3) and its chamber (slope = 0.83, r2 = 94.3). Myocardial volume,
      measured by subtracting internal (chamber) volume from external volume, was also
      calculated accurately (slope = 1.01, r2 = 96.5). The ellipsoid formula using
      directly measured diameter was only slightly less accurate. LV mass could be
      calculated by applying the specific gravity of equine myocardium, 1.05, to the
      myocardial volume. Formulae recommended for evaluating are, with M-mode
      echocardiography: [equation: see text] and with 2D echocardiography [equation:
      see text] where De is the external diameter, Di is the internal diameter, Ae the
      external area and Ai the internal area.

PMID- 9259808
TI  - Effects of treadmill elevation on heart rate, blood lactate concentration and
      packed cell volume during graded submaximal exercise in ponies.
AB  - Six ponies performed a standardised exercise test on a motorised treadmill at
      each of three randomly assigned treadmill elevations (1, 4, or 7 degrees). The
      exercise test consisted of four, 4 min increments of increasing treadmill speed
      from 1.0 to 3.4 m/sec. Heart rate, blood lactate concentration, and packed cell
      volume (PCV) were determined, during the last min of each exercise level, and at
      4 and 12 mins post exercise. Regardless of treadmill elevation, no differences
      were observed in pre-exercise heart rate (49 +/- 2) beats/min), lactate (1.2 +/-
      0.1 mM), and PCV (0.32 +/- 0.01 litres. During exercise, heart rate and PCV were
      highly correlated to treadmill speed and elevation. Peak exercise heart rates
      (determined at 3.4 m/sec) were 159 +/- 10, 182 +/- 5, and 216 +/- 6 beats/min at
      1, 4, and 7 degrees, respectively, while peak PCVs were 0.37 +/- 0.01, 0.40 +/-
      0.01 and 0.42 +/- 0.02 lit/litre at 1, 4, and 7 degrees, respectively. Blood
      lactate did not change significantly from pre-exercise levels during the exercise
      test at a treadmill elevation equal to 1 degree, but increased markedly at 4 and
      7 degrees. Peak lactates were 1.9 +/- 0.7, 5.3 +/- 1.0, and 18.1 +/- 1.5 mM at 1,
      4, and 7 degrees, respectively. There was a highly significant correlation
      between heart rate and lactate at all treadmill speeds and elevations. Therefore,
      during graded, submaximal exercise increasing treadmill elevation up to 7 degrees
      results in increases in heart rate, blood lactate concentration and PCV
      comparable to those seen with increasing treadmill speed alone.

PMID- 9259809
TI  - Cardiorespiratory drift during exercise in the horse.
AB  - The purpose of the present study was to measure the time-course and degree of
      cardiovascular and respiratory 'drift' during constant submaximal exercise in the
      horse. One Thoroughbred and four Morgan mares were instrumented for simultaneous
      measurement of respiratory and blood gases which also enabled cardiac output (Q)
      to be calculated. Data were collected at rest, and at 10, 20 and 30 mins during a
      constant workload which elicited an initial exercising heart rate (HR) of 150
      beats/min, and an approximate 15-fold increase in oxygen consumption (VO2).
      Significant cardiac and respiratory drift during exercise were observed over time
      so that ventilation increased from 750 +/- 58 to 910 +/- 49 litres/min (21 per
      cent increase) from the 10 to 30 min time-point (P < 0.05) and HR went from 154
      +/- 4 to 173 +/- 9 beats/min (mean +/- se) over the same time period (P < 0.05).
      Q also rose from 142 +/- 5 to 177 +/- 17 litres/min (P < 0.05) during the same
      interval while stroke volume (SV) was maintained. Rectal temperature (TR) and
      mixed venous lactate (LA) also showed significant increases during exercise while
      PaO2 and PaCO2 remained constant. The results indicate a significant degree of
      cardiac and respiratory drift in the horse in response to strenuous submaximal
      exercise. At the constant exercise work rate chosen, a levelling off, or
      plateauing of the selected parameters of interest was not observed. Therefore if
      a true exercising 'steady-state' was achieved, it must have occurred very early
      in the exercise bout.

PMID- 9259810
TI  - Some factors influencing plasma AST/CK activities in thoroughbred racehorses.
AB  - Sixty-six Thoroughbred horses in training (2 or 3 years of age) were studied
      during one flat racing season, to investigate the relationship between age, sex,
      time of year, dietary electrolyte imbalances and plasma aspartate
      aminotransferase/creatine kinase (AST/CK) activities. Management and training
      variations were minimised. Between February to October, monthly 24 h post
      exercise samples were collected and analysed for AST and CK activities. Sex
      and/or age were shown to have a significant effect on the occurrence of high CK
      (> 100 iu/litre) and AST (> 300 iu/litre) activities. Fillies were more likely to
      have elevated CK and AST than colts. Two-year-olds tended to have higher AST
      activities than three-year-olds. Time of year had no significant effect on the
      number of animals with high or low activities. Fourteen animals had consistently
      raised plasma AST activities (median > 300 iu/litre). Eight of these raced and
      seven won at least one race. The average daily intake of calcium, sodium,
      phosphorus and potassium was determined at each sampling time. In eight of the
      horses, the fractional electrolyte excretion (FE) of phosphate (PO4) and sodium
      (Na) was determined monthly. FE values were also determined in three horses which
      had suffered repeated attacks of the equine rhabdomyolysis syndrome. The FE, PO4
      and Na values reflected dietary intake of calcium, phosphorus and sodium
      respectively. It was not possible to determine any effect of training or a
      predisposition to equine rhabdomyolysis. No obvious differences were found
      between the resting thyroxine values of three animals with consistently low AST
      activities, six of those with consistently raised AST and three animals which had
      suffered repeated attacks of rhabdomyolysis.

PMID- 9259811
TI  - Alterations in plasma volume, plasma constituents, renin activity and aldosterone
      induced by maximal exercise in the horse.
AB  - Plasma volume (PV) decreased by 13 per cent following the completion of 1,000 m
      of maximal exercise in the horse. This study demonstrated that the critical
      reduction in PV following maximal exercise occurred within 10 mins of completion
      of exercise, as previously reported in man. Total plasma protein (TPP) increased
      by 23 per cent at 2 and 5 mins, and by 21 per cent at 10 mins post exercise.
      Therefore, it does not appear to be an accurate measurement to assess the degree
      of PV contraction in the horse. Protein was apparently added to the intravascular
      space either during or following exercise. The changes in osmolality correlated
      strongly with those in sodium, which is the primary determinant of alterations in
      plasma tonicity. The increase in osmolality (12 per cent) was similar to the
      reduction in PV (13 per cent) concluding that a transient hypotonic fluid loss
      had occurred. The increase in plasma renin activity (PRA) following maximal
      exercise was followed by an increase in aldosterone (ALD) concentration in both
      magnitude and time course. Alterations in PV should be considered when
      interpreting electrolyte and serum enzyme activity data collected following
      maximal exercise.

PMID- 9259812
TI  - Effect of show jumping on heart rate, blood lactate and other plasma biochemical
      values.
AB  - This study investigated some physiological responses to exercise performed by a
      horse during show jumping. The effects of jumping on heart rate (HR), blood
      lactate (LA) and some other blood values were studied in nine normal horses
      participating at the Belgian Junior Championship. Venous blood was sampled before
      and immediately after the show jumping and was analysed for packed cell volume,
      LA, blood glucose (GLU), total plasma protein, bicarbonate, sodium, potassium
      (K+), chloride, calcium and activities of plasma lactate dehydrogenase, creatine
      phosphokinase (CK) aspartate amino transferase and gamma glutamyl transferase
      (GGT). A heart rate recorder placed under the saddle allowed the continuous
      recording of HR from the warm-up until 2 mins after the event. The completion of
      the jumping induced significant changes in all values, except in K, GLU and GGT.
      Resting values of LA and HR were 0.53 +/- 0.05 mmol/litre and 43.9 +/- 1.9
      beats/min respectively. Post exercise LA reached a mean value of 9.04 +/- 0.9
      mmol/litre, and, during the jumping, HR rose to a peak of 191.4 +/- 3.8
      beats/min. The results of this study demonstrate that, although the speed and
      duration of such an exercise are low, show jumping represents a severe exertion
      which requires the use of anaerobic metabolism. This implies that the training
      schedule of jumpers must include power training in order to improve their
      anaerobic capacity.

PMID- 9259813
TI  - Bicarbonate loading in the thoroughbred: dose, method of administration and acid
      base changes.
AB  - Two studies were undertaken in an attempt to investigate the optimal dose, route
      and time course required to 'bicarbonate load' the Thoroughbred. During the first
      study a test solution of sodium bicarbonate (NaHCO3) and a control solution of
      water were administered via a nasogastric tube to six horses. Blood acid-base
      status was determined immediately prior to and for 24 h following intubation.
      During the second study a standardised feed was given to four horses, with and
      without NaHCO3 supplementation. This was followed by a further trial involving
      the addition of glucose and NaHCO3 to a standardised feed. During Study 1, plasma
      pH peaked 8 h after NaHCO3 intubation (7.433 +/- 0.020) and levels were still
      elevated above control values 12 h post intubation. Although there was a trend
      for blood PCO2 to be elevated above control values at all times after NaHCO3
      administration, values were only significantly different at 4 and 5 h post
      intubation. The patterns of change in plasma HCO3- and blood base-excess after
      NaHCO3 administration were similar. Values peaked between 3 and 6 h post
      intubation and were still above control values 12 h post intubation. In Study 2
      attempts to alter acid-base status by presenting NaHCO3 mixed with feed were
      unsuccessful because horses failed to consume the total mix, despite attempts to
      mask the unpalatable nature of the feed by adding glucose. The results suggest
      that future studies investigating the influence of NaHCO3 on exercise performance
      and metabolism should possibly involve administration of NaHCO3 in a greater
      quantity than is administered conventionally (0.3 g/kg). More meaningful results
      may be obtained if NaHCO3 is administered as a solution, via a nasogastric tube,
      at least 3 h prior to exercise.

PMID- 9259814
TI  - The effect of an acute hoof wall angulation on the stride kinematics of trotting
      horses.
AB  - High speed cinematography was used to describe the stride kinematics in a group
      of six, sound horses subjected to two farriery treatments, designated 'normal'
      and 'acute' hoof angulation. Normal was defined as having the dorsal hoof wall
      aligned with the pastern axis, whereas the acute hoof angulation was
      approximately 10 degrees lower than the normal angle for the individual horse.
      The acute angle was achieved by allowing the toes to grow relatively longer than
      the heels. The results of a multivariate analysis of variance showed significant
      differences between the two farriery treatments in the mode of hoof impact with
      the ground and the duration of breakover. The acute angulation was associated
      with fewer heel-first impacts and a greater number of toe-first impacts than the
      normal angulation (P < 0.01). Breakover time was prolonged with the acute
      angulation (P < 0.01). There were no significant differences between the two
      farriery treatments in stride length, duration of the suspension phase of the
      stride or duration of the stance phases of the fore or hind limbs (P > 0.05). The
      fight arc of the toe was similar for the normal and acute hoof angles, reaching
      its highest point shortly after lift off, after which the toe followed a low
      fight path. There was an elevation of the toe in preparation for heel-first or
      flat-foot impact, but when impact was toe-first the trace approached the ground
      smoothly at a more acute angle.

PMID- 9259815
TI  - The effect of an acute angulation of the hind hooves on diagonal synchrony of
      trotting horses.
AB  - High speed cinematography was used to measure the timing and distance
      characteristics of the trot in five sound horses. Two farriery treatments were
      compared: (1) normal, in which the dorsal hoof wall was aligned with the pastern
      axis in all four feet and (2) acute hind hoof angulation, in which the hind toes
      were allowed to grow relatively longer than the heels, so that the angulation was
      approximately 10 degrees lower than the normal hind hoof angle for the individual
      animal. Comparison between the two treatments showed that the acute hind hoof
      angulation was associated with significant increases in hind limb breakover time
      (P = 0.001), overreach distance (P = 0.001) and overreach duration (P = 0.017),
      whereas stride length, forelimb breakover and diagonal distance did not change (P
      > 0.05). In the majority of horses, limb movements at the start and end of the
      diagonal stance phase were slightly asynchronous, so that when the hooves were
      trimmed normally the hind limb more often preceded the diagonal forelimb at
      impact and lift off. The prolongation of hind limb breakover due to the acute
      hind hoof angulation was associated with a tendency for the hind limb to lift off
      later than the forelimb. The difference in lift off sequence between the two
      farriery treatments was highly significant (P = 0.001). During the swing phase
      the normal coordination was restored and there was no significant difference in
      the impact sequence with the normal and acute hind hoof angulations (P > 0.05).

PMID- 9259816
TI  - The role of the reciprocal apparatus in the hind limb of the horse investigated
      by a modified CODA-3 opto-electronic kinematic analysis system.
AB  - The function of the reciprocal apparatus in the hind limb of the horse was
      studied by kinematic gait analysis. For recording purposes a modified opto
      electronic CODA-3 kinematic analysis system was used. The raw kinematic data were
      corrected for skin displacement artifacts by use of recently developed correction
      models. It was concluded that contradictory findings about the coupling of tarsal
      and stifle joints by the reciprocal apparatus, when comparing in vitro and in
      vivo studies, can be fully attributed to artifacts due to the movement of the
      skin markers over the underlying bony structures, occurring in the in vivo
      experiments.

PMID- 9259818
TI  - Quantification of skin displacement in the proximal parts of the limbs of the
      walking horse.
AB  - Displacement of skin over the underlying skeletal structures in the proximal
      parts of the limbs was investigated in four walking Dutch Warmblood horses.
      Movement of the skin was visualised with self adhesive spot labels whereas that
      of the skeletal parts was visualised indirectly by means of a plastic strip
      connected to a transcutaneous Steinmann pin, driven into the bone of interest.
      Consistent results for all four horses were found. Individual and mean total
      displacements ranged from 1 to 4 cm (distal scapula) to 13 to 17 cm (caudal part
      of the greater trochanter of the femur). Displacements of this magnitude are of
      considerable importance to the interpretation of results of modern gait analysis
      techniques.

PMID- 9259817
TI  - A quantitative analysis of skin displacement in the trotting horse.
AB  - Skin displacement was investigated at 16 sites in the front and hind limbs of
      four Dutch Warmblood horses at the trot. For visualisation of the bone under the
      skin, a measuring device mounted on a Steinmann pin driven into the bone under
      investigation, was employed. Mean displacements ranged from 8 mm (X-displacements
      proximal and distal metacarpus) to 142 mm (Y-displacement caudal part of greater
      trochanter). When compared with previously determined skin displacement patterns
      at walk, mean displacements at trot were of the same magnitude whereas the shape
      of the time-displacement curve was different. The latter may be attributed to
      differences in relative duration of stance and swing phases between the walk and
      the trot.

PMID- 9259819
TI  - Transfusion in crisis: HIV in the developing world.

PMID- 9259820
TI  - Oliver Memorial Lecture 1989. The evolution and future of haemophilia therapy.
AB  - Lane (1840) first noted the beneficial effect of blood transfusion in controlling
      haemophilic bleeding following ophthalmic surgery. The appreciation that
      haemophilia is due to a plasma defect, at first thought to be prothrombin,
      coincided with the discovery of blood groups. This led in due course to the
      discovery of citrate anti-coagulant and the ability to store blood. The
      beneficial effect of citrated plasma in haemophilia led to the exploitation of
      stored blood, fresh frozen plasma, and the subsequent development of
      cryoprecipitate and factor concentrates. All this would not have been possible,
      however, without the selfless contribution of blood donors and the development of
      an organized blood transfusion service. In the United Kingdom, P. L. Oliver
      pioneered the development of blood donor panels, the London Blood Transfusion
      Service and the British Red Cross Society Blood Transfusion Service leading
      directly to the National Blood Transfusion Service; recognized as the World's
      senior service. The development of haemophilia therapy owes much, therefore, to
      Oliver's energetic and pioneering work and it is entirely appropriate that the
      first Oliver Memorial Lecture be directed to the evolution and future of
      haemophilia therapy. It is indeed an honour to be invited to deliver this Oliver
      Memorial Lecture at the combined meeting of the British Blood Transfusion Society
      and the British Society for Haematology here in Wembley.

PMID- 9259821
TI  - Infective, chronic carriers of hepatitis C virus among blood donors with no
      history of clinical hepatitis.
AB  - We investigated the infectivity of three hepatitis C virus antibody (anti-HCV)
      positive blood donors with either hepatitis B core antibodies (anti-HBc) (Nos 1
      and 2) or raised alanine aminotransferase (ALT) (No. 3). The 57 recipients of
      blood products from these donors during the period 1971-1990 were identified and
      the living 23 were tested for anti-HCV. Among these, 11 out of 14 (78%)
      recipients from Nos 1 and 2, and 1 out of 9 (11%) recipients from No. 3 were anti
      HCV positive. The former donors had high titres of anti-C100-3 and high rating
      scores in the HCV recombinant immunoblot assay (RIBA). They were evidently
      infective, chronic carriers of HCV but had no clinical signs or medical history
      of hepatitis. The latter donor had low titres of anti-C100-3 and a low RIBA
      rating score. She had clinical signs of chronic hepatitis and persistently
      elevated ALT, but only one of her recipients was anti-HCV positive.

PMID- 9259822
TI  - Hypotensive effects of stroma-free haemoglobin solutions attributable to adenine
      nucleotides.
AB  - Aqueous solutions of stroma-free human haemoglobin are being evaluated as
      potential oxygen-carrying resuscitation fluids. There are indications, however,
      that such solutions may produce toxic side-effects in vivo. Stroma-free
      haemoglobin solution produced a 50% fall in mean arterial pressure when infused
      into a small animal model despite containing very low levels of non-haem protein
      and phospholipid contaminants. This effect was not produced by haemoglobin
      solutions after extensive dialysis. Red cell-derived adenine nucleotides were
      found to be present in concentrations high enough to cause such a response (80-85
      micrograms/ml). We have developed a chromatographic assay capable of predicting
      hypotension in our animal model and consider that the complete absence of adenine
      nucleotides must be confirmed in all studies concerning the possible toxic side
      effects of stroma-free haemoglobin solutions.

PMID- 9259823
TI  - A clinical trial of red-cell concentrate prepared from blood collected in half
      strength citrate anticoagulant.
AB  - Earlier studies have indicated that plasma from blood donations drawn into half
      strength citrate anticoagulant (0.5 CPD-A2) may give improved yields of factor
      VIII:C after fractionation. It has also been shown previously that cellular
      components from blood donations drawn into 0.5 CPD-A2 have satisfactory in-vitro
      and in-vivo properties. The present study examines the clinical use of red cell
      concentrate (RCC) from 0.5 CPD-A2 blood donations. Forty-nine patients who were
      undergoing elective orthopaedic surgery and who required blood transfusion
      received 0.5 CPD-A2 RCC. A transfused control group of 107 patients received
      standard CPD-A1 RCC for their transfusion requirements. Patients in the two
      transfused groups had similar haemoglobin responses to transfusion. All patients
      experienced a moderate pyrexia following the operation. Both study groups showed
      similar responses to serum lactate dehydrogenase levels in the 2 weeks following
      surgery, and in postoperative peripheral blood platelet counts. Serious
      postoperative complications arose in both groups. In the 0.5 CPD-A2 group two
      patients had pulmonary emboli (one fatal) and one patient had a non-fatal
      myocardial infarction. Three patients had pulmonary emboli in the CPD-A1
      transfused group. These incidences of major adverse events were within the
      expected range of these complications in patients who were undergoing major joint
      replacement surgery and did not differ significantly between the study groups.
      This study indicates that red cell concentrate prepared in half-strength citrate
      anticoagulant is comparable to that prepared in CPD-A1 for patients undergoing
      orthopaedic surgery.

PMID- 9259824
TI  - Improved in-vitro quality of platelet concentrates stored in a dextrose-free
      synthetic medium.
AB  - The licensed balanced salt solution Plasma-Lyte, buffered with a clinical
      solution of sodium bicarbonate, was evaluated as a suspending fluid for platelet
      concentrates. Platelets suspended in this medium showed better pH maintenance
      over 5 days of storage compared to platelets stored in plasma (7.0 vs 6.45, P <
      0.001). This was reflected in improvements in in-vitro indicators of platelet
      viability-hypotonic shock response (79 vs 48%, P < 0.05), aggregation to paired
      agonists (86 vs 62%, P < 0.05); and platelet size distribution (104 vs 119%, P <
      0.001). Dissolved bicarbonate measurement showed less depletion of bicarbonate in
      the synthetic medium compared to plasma, which suggests a lower rate of lactate
      formation. A synthetic medium containing dextrose showed inferior platelet
      storage characteristics when compared to the plasma-lyte/bicarbonate medium in a
      paired study (Day 5, pH 6.53 vs 6.9, P < 0.05). The results suggest that
      utilization of substrates other than dextrose allows platelets to metabolize
      without the accumulation of lactate that leads to pH drops during storage in
      plasma, and continue to support the feasibility of storing platelets in a non
      plasma environment.

PMID- 9259825
TI  - SAT, a 'new' low frequency blood group antigen, which may be associated with two
      different MNS variants.
AB  - A new private blood group antigen, SAT, was identified in an NFLD-Japanese woman
      as a result of testing 10,480 blood donors with a serum containing anti-NFLD and
      anti-SAT. Three other sera were subsequently also shown to contain anti-SAT. The
      donor's family showed that SAT is inherited as a dominant character and may be
      associated with a weak M antigen. Serological and immunochemical analysis
      revealed no other aberrations in the MNS system. Study of a second SAT+Japanese
      blood donor and his family suggested that SAT is associated with an unusual MNS
      variant resulting from a hybrid glycophorin comprising the N-terminus of
      glycophorin A and the C-terminus of glycophorin B. The propositus appears to be
      homozygous for the gene that produces the putative hybrid, which differs from
      previously described glycophorin (A-B) hybrids by expressing no S, s or U
      antigen. SAT antigen, therefore, may be associated with two different MNS
      variants in the only two families in which it has been identified.

PMID- 9259826
TI  - Comparison between the erythrocyte and urinary Sda antigen distribution in a
      large number of individuals from Emilia-Romagna, a region of northern Italy.
AB  - In this study we found that the frequencies of Sda antigen on erythrocytes and
      urine of a large number of individuals from Emilia-Romagna (a region of northern
      Italy) are 0.89 and 0.93, respectively. The hypothesis that the infection by
      pyelonephritogenic Escherichia coli strains with specific adhesins for the alpha
      2,3sialyl-galactosyl structure might operate as selective agents for the high
      frequency of Sda antigen in distal renal cells is discussed.

PMID- 9259827
TI  - Presence of T-antigen on the vascular endothelium.
AB  - Bacterial neuraminidase plays an important role in the pathogenesis of some
      haemolytic anaemias. It divides neuraminic acid from the red cell surface to
      expose a hidden antigen (Thomsen-Friedenreich antigen, T). A physiologically
      circulating antibody can then react with the uncovered T and cause a rapid
      haemolysis. This study demonstrates the presence of T on human vascular
      endothelium. Similar to red cells it is exposed by the action of bacterial
      neuraminidase. The subsequent reaction with the physiological antibody could be
      involved in the pathogenesis of vascular damage observed in severe cases of
      bacterial septicaemia.

PMID- 9259828
TI  - The immune response to the HPA-1a antigen: association with HLA-DRw52a.
AB  - Antibodies to the HPA-1a antigen can elicit a condition in the new-born known as
      neonatal alloimmune thrombocytopenia (NAITP). Retrospective and prospective
      studies have shown that there is a strong correlation between the presence of HLA
      DR3, HLA-DRw52 in the mother and the antibody response to HPA-1a. HLA Class II
      molecules play an important role in the initiation of the immune response and it
      has been postulated that HPA-1a antibody production could be determined by the
      presence of a specific HLA Class II molecule at the surface of the antigen
      presenting cell. Thirty-one HPA-1a negative women with HPA-1a antibodies
      (responders) and nine HPA-1a negative women without HPA-1a antibodies (non
      responders) were recruited. They were studied using serological HLA Class I and
      Class II typing and RFLP analysis with a DR beta probe. We found that all
      responders had the HLA-DRw52a sub-specificity confirming recently published data.
      Moreover, two of the nine non-responders were also found to be HLA-DRw52a. These
      results suggest that the HLA-DRw52a molecule is necessary for HPA-1a antibody
      responsiveness but not sufficient. The results also indicate that in HPA-1a
      negative women the absence of HLA-DRw52a is associated with a very low risk of
      being antibody producers and hence, is associated with a very low risk for NAITP
      in their new-borns.

PMID- 9259829
TI  - Alloimmune neonatal neutropenia in Australian aboriginals: an unrecognized
      disorder?
AB  - Alloimmune neonatal neutropenia (ANN) is reported for the first time in two
      Australian aboriginals. Both infants displayed the typical clinical features of
      ANN with profound neutropenia which persisted for 7 weeks and only minor
      infectious episodes. However, management strategies differed for the two infants
      because in one case (complicated by uncertain paternity) serological confirmation
      of ANN was not obtained until after recovery of the infant's neutrophil count.
      The maternal antibodies could not be assigned to known neutrophil antigen
      specificities and a new antigen may be involved. The antibodies were reactive
      with > 99% of neutrophils in a Caucasian population. Aboriginals comprise 1% of
      the total population of Australia and 1-2% of the obstetric population at our
      institution. Thus, ANN may be an unrecognized disorder in this ethnic group and a
      possible cause of neonatal infection and mortality.

PMID- 9259830
TI  - Quantitation and the Rh blood group system.

PMID- 9259831
TI  - The abundance and organization of polypeptides associated with antigens of the Rh
      blood group system.
AB  - Twelve murine monoclonal antibodies, which react with human red cells of common
      Rh phenotype but give weak or negative reactions with Rh null erythrocytes, were
      used in quantitative binding assays and competitive binding assays to investigate
      the abundance and organization of polypeptides involved in the expression of
      antigens of the Rh blood group system. Antibodies of the R6A-type (R6A, BRIC-69,
      BRIC-207) and the 2D10-type (MB-2D10, LA18.18, LA23.40) recognize related
      structures and 100,000-200,000 molecules of each antibody bind maximally to
      erythrocytes of common Rh phenotype. Antibodies of the BRIC-125 type (BRICs 32,
      122, 125, 126, 168, 211) recognize structures that are unrelated to those
      recognized by R6A-type and 2D10-type antibodies and between 10,000 and 50,000
      antibody molecules bind maximally to erythrocytes of the common Rh phenotype. The
      binding of antibodies of the R6A-type and the 2D10-type, but not of antibodies of
      the BRIC-125-type could be partially inhibited by human anti-D antibodies
      (polyclonal and monoclonal) and a murine anti-e-like antibody. These results are
      consistent with evidence (Moore & Green 1987; Avent et al., 1988b) that the Rh
      blood group antigens are associated with a complex that comprises two groups of
      related polypeptides of M(r) 30,000 and M(r) 35,000-100,000, respectively, and
      suggest that there are 1-2 x 10(5) copies of this complex per erythrocyte. The
      polypeptide recognized by antibodies of the BRIC-125 type is likely to be
      associated with this complex.

PMID- 9259832
TI  - Semi-quantitative assay of D antigen site density by flow cytometric analysis.
AB  - This study describes the comparative measurement of D antigen site density using
      a fluorescent indirect antiglobulin test (FIAT) read by flow cytometry. The test
      results confirmed the continuum of D antigen strength from weakest D through to
      R2R2 and also allowed the majority of weak D samples to be adequately
      distinguished from D-negative samples.

PMID- 9259833
TI  - Human monoclonal antibodies to human blood group antigens Kidd Jka and Jkb.
AB  - Three IgM human monoclonal antibodies to Jkb, and one IgM human monoclonal
      antibody to Jka were produced from the lymphocytes of two immunized donors. Two
      of the anti-Jkb monoclonal antibodies (MS-7 and MS-9) are of the IgM (kappa)
      isotype and one (MS-8) is an IgM(lambda). The anti-Jka monoclonal antibody (MS
      15) is of the IgM(kappa) isotype. They are all specific for their respective
      antigens, and give positive agglutinations in saline by the immediate spin
      technique, even against Jk(a+b+) cells. The heterohybridomas have been shown to
      be suitable for bulk culture and produce levels of antibody that reach 18
      micrograms/ml in the spent culture supernatant. They offer considerable
      advantages over currently available reagents in terms of stability, simplicity
      and speed of use, and will provide a reliable and unlimited supply of what are at
      the moment rare and unsatisfactory antibodies.

PMID- 9259834
TI  - Mechanism of cryoprecipitation of anti-blood group B murine monoclonal
      antibodies.
AB  - In our experience, some examples of mouse monoclonal antibodies of anti-B blood
      group specificity develop a precipitate when stored at 4 degrees C. This poses
      problems during the preparation of blood grouping reagents containing anti-B, and
      in the storage and use of such reagents. Here we show that this problem can be
      circumvented by alteration of the glycan moiety of the secreted immunoglobulin,
      either by glycosidase treatment of the partially purified immunoglobulin, or by
      the addition of glycan processing inhibitors to the hybridoma cell cultures.
      These findings have importance for the manufacture of monoclonal antibodies, and
      highlight a possible new role for carbohydrate in immunoglobulin interaction and
      immune complex formation.

PMID- 9259835
TI  - Post-transfusion hepatitis after open-heart surgery in Finland--a prospective
      study.
AB  - A countrywide prospective study on open-heart surgery patients was performed
      between 1987 and 1989 to determine the prevalence and nature of post-transfusion
      hepatitis in Finland. Altogether 685 coronary by-pass operation patients, who
      received on average 12.3 units of blood products, were postoperatively followed
      for 6 months. Ten blood samples were drawn from each patient. Hepatitis was
      diagnosed when the alanine aminotransferase values exceeded the upper normal
      value 2.5 times in one sample and twice in another, and non-viral causes could
      reasonably be excluded. Eleven hepatitis cases (1.6%) were recorded with a mean
      incubation period of 8.4 weeks; all represented the non-A, non-B type. The
      majority had mild symptoms or were asymptomatic but two became icteric. Six
      patients (55%) had abnormal alanine aminotransferase values for at least 6
      months, which indicates possible chronicity. These 685 open-heart surgery
      patients received a total of 8,436 units of blood products; thus the rate of
      NANBH cases per 1000 units was as low as 1.3. This is less than recently reported
      in six other prospective studies.

PMID- 9259836
TI  - Post-transfusion hepatitis C in Finland.
AB  - Six of 11 (55%) non-A, non-B hepatitis (NANBH) patients seroconverted to
      hepatitis C virus antibody (anti-HCV) positivity 8-16 weeks after transfusions in
      a prospective post-transfusion hepatitis study on 685 open-heart surgery patients
      in Finland. Five of them had a seropositive donor, and two of the five non
      converted NANBH patients had received an anti-HCV positive unit. Among 36 studied
      donors who were positive in the anti-HCV ELISA, reactivity of both the antigen
      bands in a recombinant immunoblot assay (RIBA) for anti-HCV was significantly
      associated with NANBH (P < 0.00005) in the recipient. In addition, infective anti
      HCV positive donors had raised ALT values more often than seropositive donors
      which caused no seroconversion or infection in the recipients (P = 0.0001).

PMID- 9259837
TI  - Follow-up study on 24 patients with nomifensine-induced immune haemolytic
      anaemia.
AB  - There is as yet only scarce information regarding the natural history and long
      term clinical sequelae of patients who survive the acute complications of severe
      drug-related immune haemolysis, the effect of the mode of drug administration for
      sensitization and possible alterations of serological characteristics of drug
      dependent antibodies during the postsensitization period. We therefore followed
      24 patients with nomifensine-induced haemolytic anaemia for up to 6 years after
      the haemolytic attack. All patients had suffered from a severe haemolytic
      episode. None of the patients showed any abnormal findings upon reinvestigation
      (complete history and physical examination; extended biochemical and
      haematological laboratory status), particularly with respect to renal function.
      Drug-dependent antibodies remained detectable in 19 of 21 sera, while drug
      independent autoantibodies, demonstrable in six patients during the acute phase
      of haemolysis, could no longer be detected. With regard to the mode of drug
      administration, the majority of patients (15 out of 24) had developed the
      haemolysis at the beginning (immediately after a single dose) or during a second
      course of drug therapy (n = 8 and 7, respectively). The immune response did not
      appear to be dose- or time-dependent. This study confirms the benign long-term
      prognosis of patients who survive life-threatening complications in drug-induced
      immune haemolytic anaemia. In addition, it indicates that drug-dependent
      antibodies may remain detectable over long periods of time, and that irregular
      drug administration might be associated with a higher risk of drug sensitization.

PMID- 9259838
TI  - A pilot study of antithrombin replacement in intensive care management: the
      effects on mortality, coagulation and renal function.
AB  - A prospective, randomized, controlled trial to examine the effects of
      antithrombin supplementation on mortality, coagulation and renal function has
      been carried out on 132 intensive care patients. Antithrombin activity was
      measured in all patients on admission to the intensive care unit (ICU). Patients
      with an antithrombin activity of less than 70% were randomized to either receive
      antithrombin replacement or to act as controls. Antithrombin activity was
      maintained above 70% in the treated patients throughout their stay on ICU. Ninety
      three patients had an antithrombin activity of less than 70% and 35 received
      replacement therapy. Patients with antithrombin activity below 70% remained on
      the ICU significantly longer and had a significantly higher mortality rate than
      patients with antithrombin activity above 70%. Antithrombin supplementation
      neither reduced mortality nor shortened the intensive care stay. Fifty patients
      with reduced antithrombin activity remained on the ICU for at least 4 days, 25
      received antithrombin and 25 acted as controls; coagulation parameters and renal
      function have been monitored in these patients. Fibrinogen concentration and
      platelet count were unaffected by antithrombin replacement. Antithrombin
      supplementation did not appear to reduce the incidence of impaired renal function
      in sepsis, trauma and postoperative patients. The creatinine clearance fell below
      20 ml/min in eight patients in the no-treatment arm while by comparison only
      three patients in the treatment arm developed impaired renal function. Our study
      does not demonstrate a clear role for the use of antithrombin supplementation in
      intensive care, however the finding that antithrombin reduced renal impairment is
      encouraging and a larger study to confirm this finding is at present underway.

PMID- 9259839
TI  - Overestimation of fetomaternal haemorrhage by the acid-elution technique in
      mothers with beta-thalassaemia minor.
AB  - In Rh-negative women, it is important to quantify the magnitude of an Rh-positive
      fetomaternal haemorrhage (FMH) so that sufficient Rh immune globulin (RhIg) can
      be administered early in the post-partum period to prevent alloimmunization. The
      standard post-partum dose of RhIg varies from 100 micrograms in the UK to 300
      micrograms in North America. It is therefore important to identify all Rh
      negative women who have had an FMH greater than 10 ml in the UK or greater than
      30 ml in North America because an FMH greater than these amounts will affect the
      dose of RhIg that is administered. As acid-elution techniques can overestimate
      the magnitude of an FMH in the presence of an elevated maternal haemoglobin F
      level, we performed a prospective study to determine how often this occurred. Of
      1,894 consecutive Rh-negative mothers who delivered Rh-positive infants, whose
      blood was screened for an FMH greater than 10 ml of fetal blood using an acid
      elution procedure, 11 were found to have an FMH over 10 ml. In five of these 11
      women, the volume of FMH was less than 10 ml using an alternative technique
      (rosette test) to assess the FMH size. Six of these women were found to have beta
      thalassaemia minor on the basis of a low MCV, and high haemoglobin A2 and/or high
      haemoglobin F levels. In five of these the FMH was significantly overestimated by
      the acid-elution technique compared to the rosette technique. Therefore, in the
      presence of a maternal condition, which may result in an elevated haemoglobin F
      level, an FMH estimated to be over 10 ml in the UK or 30 ml in North America
      using an acid-elution procedure, should be confirmed by an alternative technique,
      which does not involve the estimation, directly or indirectly, of haemoglobin F.

PMID- 9259840
TI  - Three decades of reference serology.
AB  - I have tried to show that blood group serology developed rapidly out of necessity
      and demonstrated a high degree of polymorphism on red cells that was unmatched at
      that time in man. With new knowledge, these observations have proved to be
      accurate and informative and correlate well with subsequent biochemical and
      molecular studies on the antigenic structures, in spite of the fact that they
      were achieved by relatively simple technology. Serology still has the capacity to
      focus on points of interest and even to solve problems, albeit in conjunction
      with other modern and more sophisticated techniques. It provides a good
      discipline for any scientist to make unbiased and objective studies.

PMID- 9259841
TI  - The pH, conductivity and osmolality of low ionic strength solutions used within
      the U.K. for the antiglobulin test.
AB  - Low ionic strength solutions (LISS) for use in the antiglobulin test were
      obtained from 356 U.K. laboratories. Of the 324 laboratories using LISS to
      suspend the test red cells and who returned details of their LISS technique, 15
      used unequal proportions of red cell suspension and serum despite the LISS being
      formulated for use with equal proportions. Of the 22 laboratories mixing LISS
      with serum and red cells suspended in a normal ionic strength medium, four used a
      LISS preparation formulated for a LISS-suspension technique and three used a
      commercially available LISS-addition preparation using proportions of red cells,
      serum and LISS not recommended by the manufacturer. The mean (standard deviation)
      pH, conductivity and osmolality of the 334 LISS preparations for LISS-suspension
      was 6.9 (0.2), 4.1 (0.4) mS/cm and 298 (15) mmole/kg, respectively. It is
      suggested that attention should be paid to the osmolality and, particularly,
      conductivity during the preparation of LISS because values were observed that
      were clearly outside the acceptable range cited in the Guidelines for the Blood
      Transfusion Services in the United Kingdom, i.e. pH 6.7 +/- 0.2, conductivity 3.7
      +/- 0.3 mS/cm and osmolality 295 +/- 5 mmole/kg.

PMID- 9259842
TI  - Evaluation of the ID-gel test for antibody screening and identification.
AB  - A gel technique for the detection of red blood cell (rbc) antigen-antibody
      reactions was evaluated for use in antenatal antibody screening and
      identification procedures. The evaluation was undertaken on 3,900 random
      antenatal samples. Results obtained in the gel test system were compared with
      those obtained from parallel testing using conventional serological methods. The
      ID gel system detected 148 (3.7%) red cell antibodies, compared with 95 (2.4%)
      using traditional techniques. The number of non-specific antibodies and false
      positive screens were reduced using the gel test system. Antibody titres
      performed using the gel system were more sensitive than with our tube IAT method.
      The gel system was easy to use and gave reliable, reproducible results. Antibody
      detection rates were enhanced compared with our existing routine techniques.

PMID- 9259843
TI  - Evaluation of a solid phase red cell adherence technique for platelet antibody
      screening.
AB  - Solid-phase red-cell adherence (SPRCA) techniques in platelet serology are used
      mainly for crossmatching. A SPRCA method for general diagnostic application was
      evaluated in parallel with the platelet suspension immunofluorescence test
      (PIFT). Of 149 patient sera sent for investigation of thrombocytopaenia, 76 were
      negative and 59 positive when studied by both methods, eight positive by PIFT
      only and six positive by SPRCA only. The reactivity observed for 24 sera
      containing HLA antibodies tested with chloroquine-treated and untreated platelets
      was similar for both methods. All of 14 sera containing quinine-associated
      antibodies reacted strongly to both techniques in the presence of added quinine.
      In comparison, however, whereas all sera were nonreactive to SPRCA in the absence
      of added quinine, and with PIFT, seven of the sera reacted weakly. Titration
      studies with three examples of anti-PlA1 and five sera containing HLA antibodies
      generally showed a one doubling dilution lower titre with the SPRCA procedure.
      End-point interpretation, however, was more readily achieved with the SPRCA
      method. The SPRCA technique displays similar sensitivity and specificity to the
      PIFT and is recommended for use by routine hospital laboratories to screen
      platelet antibodies.

PMID- 9259844
TI  - The MiIII phenotype among Chinese donors in Hong Kong: immunochemical and
      serological studies.
AB  - The incidence of the MiIII phenotype among Chinese blood donors in Hong Kong was
      found to be 6.28%. Eleven individuals apparently homozygous for the MiIII gene
      were detected by immunoblotting with monoclonal antibodies R1.3 and R18. R1.3
      detects an identical epitope on both glycophorins A and B and R18 detects a
      different epitope on glycophorin A. Immunoblotting with R1.3 showed an absence of
      bands corresponding to normal glycophorin B. Immunoblotting with R18 showed an
      absence of a 58 K band, which corresponds to a heterodimer of normal glycophorin
      B complexing with the MiIII component, found in MiIII heterozygotes. In two
      families with apparent MiIII homozygous individuals, both parents of the
      propositi had the MiIII phenotype which implies normal autosomal inheritance of
      the MiIII gene. In another family, only one parent had the MiIII phenotype and
      the presence of an Su gene is postulated to explain the immunochemical and
      serological findings.

PMID- 9259845
TI  - Presence of glycosyltransferase inhibitors in the sera of patients with long-term
      surviving ABO incompatible (A2 to O) kidney grafts.
AB  - In the sera of blood group O recipients with long-term surviving blood group A2
      kidney grafts, inhibitors of A-glycosyltransferase (alpha-3-N-acetyl-D
      galactosaminyl transferase) have been identified in four out of six patients. The
      inhibitors seem to be of IgG antibody nature and do not appear until at least 1
      year after transplantation. The inhibitors are also active against B-transferase
      (alpha-3-D-galactosyl transferase) as well as against A-glycosyltransferase of
      pig origin. The importance of these A-glycosyltransferase inhibitors is not
      clear. They may have a modifying effect on the antigenic expression of the graft.
      The immunogenicity of soluble glycosyltransferases is well known and the
      development of antibodies against them might prevent their enzymatic activity.

PMID- 9259846
TI  - The treatment of autoimmune thrombocytopaenic purpura with anti-D immunoglobulin:
      similar platelet responses in homozygous and heterozygous Rh(D) positive
      patients.
AB  - Twenty-one patients with autoimmune thrombocytopaenic purpura (AITP) were treated
      with anti-D immunoglobulin. There was no significant difference with low and high
      dose anti-D treatment in the platelet count response between homozygous and
      heterozygous Rh(D) positive patients. The heterogeneous responses seen in Rh(D)
      positive AITP patients treated with anti-D immunoglobulin cannot therefore be
      explained by differences in Rh(D) phenotypes.

PMID- 9259847
TI  - Platelet apheresis for extreme thrombocytosis in an 11-year-old girl with CML.
AB  - This report describes the dramatic reduction in the platelet count and ablation
      of symptoms by consecutive platelet apheresis in a young girl with CML who
      presented with an extremely high platelet count of 10,320 x 10(9)/l. Extreme
      thrombocytosis, although quite rare, can be symptomatic and life-threatening in
      paediatric patients and should be considered an emergency. The mechanical removal
      of platelets by apheresis is effective therapy and should begin as soon as
      possible.

PMID- 9259848
TI  - Antibody to hepatitis C virus in blood donors found positive for other agents. I.
      Treponemal infection.
AB  - Stored serum samples from 169 blood donors found positive for TPHA were tested
      for antibodies to hepatitis C virus (anti-HCV) and to hepatitis B core (anti
      HBc), as evidence of previous HBV infection, a condition known to be sexually
      transmissible. Only three donors were positive with a 'first generation' anti-HCV
      and all three failed to confirm with a recombinant immunoblot assay (RIBA). In
      contrast, 33 (19.5%) of the TPHA-positive donors were positive for anti-HBc. The
      results suggest that sexual transmission is not a major factor in the spread of
      HCV.

PMID- 9259849
TI  - Antibody to hepatitis C virus in blood donors found positive for other agents.
      II. Anti-HIV-1.
AB  - Stored serum samples from 24 blood donors confirmed positive for anti-HIV-1 were
      tested for antibody to hepatitis C virus (HCV). Those repeatedly reactive using
      the anti-HCV ELISA screening test were retested by the HCV recombinant immunoblot
      (RIBA). Risk-factors for the contraction of HIV infection that had been elicited
      at formal counselling sessions were evaluated in relation to HCV/HIV modes of
      infection. The only two donors confirmed to be anti-HCV positive both admitted to
      intravenous drug use.

PMID- 9259850
TI  - Promoting blood donation: a study of the social profile, attitudes, motivation
      and experience of donors.
AB  - This study investigated how to improve the recruitment of blood donors, their
      retention as active donors and their response to call-up. A total sample of 9,000
      non-donors, lapsed donors and current donors was examined in three programmes to
      determine the sex, age and social profile of donors; the attitudes of the
      population to blood donation; the motivating forces prompting people to give
      blood; the de-motivating forces preventing them; the image of the blood donor in
      society and the image of the National Blood Transfusion Service (NBTS). The
      profile of blood donors, with small variations, reflects that of the population.
      The experience of blood donation is widespread with 27% of the population either
      current or lapsed donors. The image of both blood donors and the NBTS was found
      to be very positive. The main force motivating donors is an awareness of patient
      need complemented by awareness that the need may one-day be personal. NBTS
      strategy will concentrate on reinforcing the need for blood donors and enhancing
      the experience of donors at blood donor sessions.

PMID- 9259851
TI  - The effect of intravenous immunoglobulin on placental transfer of a platelet
      specific antibody: anti-P1A1.
AB  - The isolated perfused lobule of human placenta was used as an in-vitro model to
      study the effect of intravenous immunoglobulin (IVGG) on the placental transfer
      of a human platelet-specific antibody (anti-P1A1). Normal human IgG was shown to
      transfer from the maternal to the fetal circulation of the placental model after
      a lag period of 2-3 h. IVGG also transferred across the placenta but only after a
      longer lag period (3-4 h) than normal human IgG at the same concentration, which
      suggests that IVGG may contain a factor that inhibits the transfer of its own
      component IgG. The sensitive Western immunoblotting technique was used to
      demonstrate progressive transfer of anti-P1A1 antibody to the fetal circulation
      after a 2-3 h lag period. When IVGG and anti-P1A1 antibody were added
      simultaneously to the maternal circulation, the transfer of platelet-specific
      antibody was strongly inhibited by IVGG. The inhibitory effect of IVGG on anti
      P1A1 antibody transfer was consistent for three different batches of the same
      IVGG product (Sandoglobulin). These studies provide the first scientific data to
      support the use of IVGG to inhibit antiplatelet antibody transfer as part of the
      antenatal management of neonatal alloimmune thrombocytopenia.

PMID- 9259852
TI  - Transfusion-induced immunosuppression and red cell clearance.
AB  - While blood transfusion is increasingly implicated in the aetiology of tumour
      recurrence, the mechanism of this effect is unclear. Cancer-bearing patients are
      known to have factors in their sera which depress the function of normal
      lymphocytes. It is possible that blood transfusion accentuates this natural
      suppression. An animal model was therefore developed to study the effect of blood
      transfusion on humoral immunosuppressive activity and its possible relationship
      to red cell clearance. WAG rats given a transfusion of chromium-labelled
      allogeneic but blood-group compatible DA rat blood, developed significantly
      increased (P < 0.001) levels of lymphocyte suppressive factors in plasma (maximum
      at 7 days) which coincided with accelerated red cell clearance (t1/2 = 7 days). A
      transfusion of syngeneic WAG blood caused only a small transient increase in
      plasma suppression and red cells were cleared at a normal rate (t1/2 = 13 days)
      consistent with previous studies. However, when syngeneic WAG red cells were
      lysed and the red cell membranes infused there was a rapid increase in plasma
      suppression (P < 0.001), similar to but less prolonged than that achieved with
      allogeneic blood. The immunosuppressive effect of blood transfusion may result
      from accelerated clearance of allogeneic or damaged syngeneic red blood cells.

PMID- 9259853
TI  - Quantification of IgG on erythrocytes of patients and normals by a radio-ligand
      binding assay.
AB  - A monoclonal IgG anti-human IgG, 1B12, was used in a radio-ligand-binding assay
      to quantify IgG on erythrocytes of patients and normals. The assay detected a
      range of 10-700 IgG molecules. Good correlation was achieved between the number
      of molecules and the strength of agglutination in antiglobulin tests performed in
      capillary tubes. The assay was capable of detecting subagglutinating immune bound
      IgG on erythrocytes from patients with systemic lupus erythematosus (SLE).

PMID- 9259854
TI  - Erythroblast- and erythrocyte-bound antibodies in alpha and beta thalassaemia
      syndromes.
AB  - Thirty-five Thai patients with various alpha-thalassaemia (alpha-thal 1/alpha
      thal 2, alpha-thal 1/HbCS, HbCS/HbCS) and beta-thalassaemia (beta-thal/HbE,
      severe and mild form, HbE/HbE) syndromes were examined for the presence of
      immunoglobulins and C3d on o-tolidine positive erythroblasts in the bone marrow,
      and for the amounts of IgG of some specificities bound to circulating
      erythrocytes. In mild, but not in severe beta-thal/HbE and in alpha-thalassaemia,
      the percentages of Ig-positive erythroblasts were significantly higher than in
      controls and correlated well with the percentage of IgG-positive erythroblasts.
      By contrast, the percentages of IgM and C3d positive erythroblasts were low and
      similar in thalassaemic and control marrows. A substantial proportion of
      thalassaemic patients showed more erythrocyte-bound IgG than controls, but
      statistically significant elevations were seen only in severe beta-thal/HbE.
      Within a particular syndrome erythrocyte-bound IgG was more abundant in
      splenectomized than non-splenectomized subjects. It showed specificity for
      spectrin in some beta-thalassaemic patients and for band 3 protein in several
      individuals with alpha- or beta-thalassaemia. The results suggest that IgG
      antibodies play a role in the haemolysis of thalassaemia and that they are likely
      to be involved in the ineffective erythropoiesis in at least some of the
      syndromes studied.

PMID- 9259855
TI  - A murine monoclonal anti-N, BIRMA-N, suitable for blood grouping in an automated
      system.
AB  - BIRMA-N, a murine monoclonal anti-N antibody of the IgG1 subclass, was assessed
      for suitability as a blood grouping reagent on the Olympus PK7100 automated blood
      grouping machine. At a selected dilution and over the pH range 5.0-8.0, the
      antibody performed accurately in this system as confirmed by parallel manual
      testing of donor blood samples with human anti-N and commercial monoclonal anti-N
      reagents. These findings show BIRMA-N to be extremely suitable for N typing blood
      samples in an automated system providing a convenient, objective and cost
      effective method for large scale typing of the blood donor population.

PMID- 9259856
TI  - A family showing inheritance of the Anton blood group antigen AnWj and
      independence of AnWj from Lutheran.
AB  - A 43-year-old Arab woman was found to be negative for the high incidence AnWj
      antigen and her serum contained anti-AnWj. Two of her seven siblings were also
      AnWj-negative, which provides evidence for the first time that the AnWj-negative
      phenotype may be an inherited character. Blood groups of the family, in which the
      parents of the proposita are consanguineous, show that AnWj is not part of the
      ABO, Rh, MNSs, Kell, Duffy, Kidd, Xg and, notably, Lutheran blood group systems
      and neither is it X or Y linked.

PMID- 9259857
TI  - Superfecundation identified by HLA, protein, and VNTR DNA polymorphisms.
AB  - Parentage analysis has revealed a high probability that a man accused of
      paternity is the biological father of a male child. The child in this study,
      however, was the twin of a female child who could not have been fathered by the
      accused man. The mother of the children subsequently accused a second, unrelated
      man, who was excluded from paternity of the boy, but was very probably the
      biological father of the girl.

PMID- 9259858
TI  - The preservative-exchange method using a sextuple-bag system for a 10-week
      storage period of red blood cells.
AB  - Prolonged storage of red blood cells in a liquid state was achieved by replacing
      the preservative using a sextuple-bag system. The bag system consists of one
      primary bag containing citrate-phosphate-dextrose (CPD) solution, three satellite
      bags containing saline-adenine-glucose-phosphate-maltose (SAGP-maltose) solution,
      and two empty satellite bags to remove plasma and buffy coat. Preservative can be
      exchanged three times in this closed system. The system is able to supply
      nutrients, such as glucose, and to remove harmful metabolites, such as lactic
      acid, by exchanging the preservative during storage. As a result, red cells
      stored by this method showed much higher levels of total adenylate and
      morphological score after the second preservative exchange, when compared with
      red cells stored by the conventional method (P < 0.01). Judging from these two in
      vitro parameters, red cells may tolerate storage for at least 10 weeks in a
      liquid state. This method might be useful for 'predeposit autologous
      transfusion', as it is more convenient and more cost effective than the freeze
      preservation method.

PMID- 9259859
TI  - Lipolytic enzyme and phospholipid level changes in intraoperative salvaged blood.
AB  - Autotransfusion is becoming increasingly popular, mainly because it eliminates
      the risk of disease transmission. One of the techniques available is intra
      operative blood salvage and retransfusion with or without washing of the
      collected blood. The blood collected during this process is subjected to a
      variety of chemical and physical insults which can alter the normal composition
      of the plasma by activating plasma and cellular homeostatic mechanisms. In this
      study, we measured the plasma levels of total phospholipids, lysolecithin and non
      esterified fatty acids, and the lipolytic enzymes phospholipase A2 (PLA2) and
      lipase in the salvaged blood before and after washing. In the unwashed salvaged
      blood the mean levels of PLA2, non-esterified fatty acids and lysophospholipids
      increased by 144, 96 and 149%, respectively, while those of total phospholipids
      and lipase did not change to any extent. All these substances were reduced to
      well below the patients circulating plasma levels by washing the collected blood.
      The changes indicate that the lipid profile of salvaged blood is significantly
      altered and that potentially dangerous substances such as PLA2 and its
      metabolites, lysolecithin and non-esterified fatty acids, are present in
      increased amounts. Washing the blood is recommended prior to reinfusion.

PMID- 9259860
TI  - Is there a wastage of resources due to non-specificity of anti-HIV ELISAs?
AB  - A library of anti-HIV ELISA 'grey-area' and repeatably reactive samples sent for
      confirmatory testing, were retested using a second technique, the modified
      (Fujirebio Gelatin Particle) agglutination test (MAT). On testing 224 grey-area
      reactive samples, only four were found to be reactive with this second test. On
      retesting a further 259 ELISA repeatably reactive samples, of which only 33 were
      confirmed to be anti-HIV-1, only 45 were reactive by MAT; these included the 33
      confirmed as positive samples, thereby reducing the false-positive from 226 to
      12. The introduction of this second technique supported our decision to cease the
      referral of grey-area samples. It also demonstrated the high prevalence of non
      specificity of repeatable reactivity associated with some of the most specific
      ELISA kits currently available.

PMID- 9259861
TI  - British Association of Dermatologist annual meeting. Harrogate, United Kingdom, 1
      5 July 1997. Abstracts.

PMID- 9259862
TI  - 12th International Interdisciplinary Conference on Hypertension in Blacks.
      London, England, July 20-23, 1997. Abstracts.

PMID- 9259863
TI  - 20th Annual meeting of the Japan Neuroscience Society. Sendai, Japan, July 16-18,
      1997. Abstracts.

PMID- 9259864
TI  - EUROTOX '97. Diversification in Toxicology: man and environment. Aarhus, Denmark,
      June 25-28, 1997. Abstracts.

PMID- 9259866
TI  - [Joint annual meeting of the Swiss medical societies. Abstracts].

PMID- 9259865
TI  - 21st congress of the Scandinavian Association of Urology. Copenhagen, Denmark,
      June 4-7, 1997. Abstracts.

PMID- 9259867
TI  - [Angiotensin II antagonist for heart insufficiency].

PMID- 9259868
TI  - [Annual International Meeting of Cardiology. Paris, France, 29-30 May 1997.
      Abstracts].

PMID- 9259869
TI  - Spinal anesthesia: some considerations.

PMID- 9259871
TI  - Intravenous infusions of nifedipine: an alternative for the prevention of
      hypertension in eye surgery under local anesthesia.
AB  - In order to control critical rises of blood pressure during the peri-operative
      period in elderly hypertensive patients, the effectiveness of a continuous
      intravenous infusion of nifedipine was studied. In a double blind study, patients
      (n = 60) who underwent eye surgery under local anesthesia were divided randomly
      into three groups. Patients who were found to have 200 > SBP > 160 and 120 > DBP
      > 90 mmHg as the previous day of surgery, as well as patients who did not receive
      any anti-hypertensive treatment regimen during the last week before surgery, were
      selected. Five min before performing local anesthesia, a continuous infusion of
      nifedipine at two different rates of 0.65 mg/h and 1.25 mg/h, was administered in
      groups A and B respectively, whereas group C received a placebo. SBP, DBP and HR
      were recorded every 5 min. for an hour. Statistically significant differences
      among the profiles of the three groups were found. The control group had a higher
      SBP/DBP. None of the groups, showed significant changes in HR. In conclusion, the
      intravenous infusion of nifedipine in a dose 1.25 mg/h, seems to control the
      hypertensive phases of blood pressure, without dropping to any unduly low level,
      risking undesirable side effects in elderly hypertensive patients during
      perioperative period.

PMID- 9259870
TI  - Intravenous regional anesthesia. Evaluation of 4 different additives to
      prilocaine.
AB  - Intravenous regional anesthesia (IVRA) is an effective method of producing
      anesthesia of the extremities. Disadvantages are the rapid loss of anesthesia
      after the deflation of the tourniquet and the rapid development of postoperative
      pain. This study compared the effect of four different additives to prilocaine
      with saline on the development of a complete sensory block, on the return of
      sensory function after deflation of the tourniquet and on the development of
      postoperative pain after IVRA for minor orthopedic surgery of the arm. Seventy
      five patients, ASA class 1 or 2, were randomly divided into 5 groups. All
      patients received 30 ml. of prilocaine 1%, together with 5 ml. of additive. In
      group 1, the additive was saline, in group 2 bupivacaine 0.25%, in group 3
      clonidine 150 micrograms in saline, in group 4 sufentanil 25 micrograms in saline
      and in group 5 tenoxicam 20 mg. The development of a complete sensory block
      proved significantly faster in the patients receiving sufentanil (4.8 min.) as
      compared to plain prilocaine (7.5 min.). The return of the sensory function was
      comparable for all groups. Postoperative pain scores were significantly better in
      the clonidine and tenoxicam groups.

PMID- 9259872
TI  - Effect of low dose fentanyl-droperidol administration on respiratory drive,
      respiratory pattern and gas exchange in ASA 1 spontaneously breathing patients.
AB  - The aim of this study was to investigate the short term effects of low doses of
      fentanyl and droperidol on central respiratory drive, gas exchanges, respiratory
      pattern and inspiratory impedance of the respiratory system in a group of ASA 1
      patients. Fourteen ASA 1 patients scheduled for minor surgery or endoscopic
      procedures were enrolled in the study, thirty minutes before the intervention.
      During spontaneous breathing of air we evaluated, by recording airflow, airway
      opening pressure and volume, the following variables: Respiratory Rate (RR),
      Tidal Volume (TV), Total respiratory cycle, Inspiratory and Expiratory Time (Ti,
      Te), mean inspiratory flow, P0.1, pH, PaO2 and PaCO2. After obtaining basal
      measurements, droperidol and fentanyl were injected and the above mentioned
      variables evaluated at 5 min (T1), 10 min (T2), 15 min (T3) intervals. Arterial
      blood was age, sampled at T3 for blood gas evaluation. The administration of
      droperidol (0.1 mg/kg) and fentanyl (0.002 mg/kg) significantly reduced P0.1 and
      Tidal Volume comparing basal with T1 and, T2 values. The other variables did not
      significantly modify. Two patients showed transient respiratory rhythm
      abnormalities in the first 180 sec following the administration of
      droperidol+fentanyl. Our results suggest that, in ASA 1 patients,
      droperidol+fentanyl preoperative administration, has no significant effects on
      respiratory pattern, respiratory impedance and gas exchanges: however also at low
      doses, the association of droperidol+fentanyl can reduce the respiratory center
      activity, expressed as P0.1, with a consequent reduction in Tidal Volume.

PMID- 9259873
TI  - Accidental overdosing with intraspinal morphine caused by misprogrammation of a
      Synchromed pump: a report of two cases.
AB  - Spinally administered opioids must be a last step in the therapeutical arsenal of
      chronic benigne pain. It is an invasive technique not free from adverse effects.
      Two chronic pain patients received an implantable Synchromed pump for treatment
      with spinal opiates after a trial period of resp. 3.5 and 5.5 months. Due to a
      misprogrammation (both on the same day) they received very high doses of spinal
      opiates. This caused relatively few side effects, which did not seem to require
      immediate treatment. A short time development of tolerance to life threatening
      side-effects has been proven by this accidental administration of high-dose
      intraspinal opiates. It is critical that care providers are knowledgeable and
      well-trained about implantable infusion systems. Programmation and refills must
      always be performed with care.

PMID- 9259874
TI  - Anesthetic management of a patient combining myotonic dystrophy and obesity.
AB  - We describe the anesthetic management of an obese myotonic patient who underwent
      bilio-pancreatic diversion for severe obesity. A female, 35 years old (weight 137
      kg, height 160 cm, excess body weight 120%) suffered from myotonic dystrophy and
      obesity, complicated by a mild heart failure and restrictive disease. Induction
      of anesthesia and tracheal intubation were performed after propofol (1 mg/kg).
      Anesthesia was maintained with isoflurane and fentanyl muscular blockade by
      vecuronium bromide. Perioperatively extensive hemodynamic monitoring has been
      performed. The patient was discharged successfully the 12th day postoperatively.
      One year later she had lost 50 kgs of body weight; oxygen blood tension and
      pulmonary function tests were greatly improved.

PMID- 9259875
TI  - Towards a new chronology of ether anesthesia in Europe.

PMID- 9259876
TI  - Structural and architectural changes during arterial development and the role of
      hemodynamics.
AB  - Hemodynamics is a major determinant in the anatomical and mural architectural
      development of the arterial tree. Arterial intimal proliferation commences in
      utero at specific anatomical sites often appearing eccentric in transverse
      section and precedes more diffuse concentric thickening. Regarded as an inherent
      structural component of the wall or an adaptive mural response to increasing
      hemodynamic stresses concomitant with growth, its occurrence in utero and in
      lower animals, though generally supportive of this view, ignores qualitative
      changes. Further doubt derives from the retrogressive destructive nature of
      structural changes in the arterial wall in the young, individual differences and
      their continued progression after birth and maturation. It is postulated that
      concomitantly with arterial development the associated degenerative changes are
      attributable to hemodynamically induced bioengineering fatigue caused by
      longitudinal stretching and circumferential distensile effects of the pulse waves
      and by lesser vibrations generated by flow at sites of predilection for
      compensatory intimal thickening. This intimal proliferation is the compensatory
      reparative response to loss of tensile strength of mural constituents and of the
      vessel wall as a whole.

PMID- 9259877
TI  - The different responses of the female mouse thymus to estrogen after treatment of
      neonatal, prepubertal, and adult animals.
AB  - Contrary to the common description of estrogen-induced thymus atrophy we have
      observed a thymus enlargement after treatment of neonatal female mice with
      estrogen. We now describe an age-dependent difference in the estrogen response
      (enlargement, atrophy) as well as mechanisms relevant to the response. Groups of
      female NMRI mice were treated with estrogen (diethylstilbestrol, DES) at
      different 5-day periods in prepubertal (day 1-5, day 6-10, day 30-34) or
      postpubertal life (days 48-52). All the treatment groups showed a reduced thymus
      weight 4 days after the last treatment but later responses differed. Neonatal DES
      treatment resulted in an ovary-independent thymus enlargement 8 weeks after the
      treatment when the cortical part was relatively larger than in controls;
      treatment on days 30-34 was followed by a rebound type of regeneration; the acute
      weight reduction after treatment on days 48-52 was normalized 16 days later.
      Neonatal DES treatment transiently depressed the number of thymic S phase cells 4
      days after the treatment while apoptosis was similar in controls and DES females.
      The estrogen receptor pattern was not affected by DES. The number of white blood
      cells was temporarily depressed while the bone marrow cellularity was still
      reduced in 8-week-old females. Neonatal treatment with an LH-releasing hormone
      antagonist reduced thymus weight at 8 weeks but had no effect on the DES-induced
      enlargement. The delayed-type hypersensitivity response developed differently in
      controls and DES females. The thymus enlargement after neonatal estrogen
      treatment could be the result of an increased immigration of precursor cells into
      the thymus and/or a defect maturation/emigration mechanism. Further studies on
      different cell subsets are necessary to explain the mechanism behind the thymus
      enlargement.

PMID- 9259878
TI  - Ultrastructure of the rat periodontal ligament as observed with quick-freeze,
      deep-etch and replica methods: arrangement of collagen and related structures.
AB  - The ultrastructure of the periodontal ligament of rat molars was examined with
      the quick-freeze, deep-etch replica methods. It was mainly composed of elongated
      fibroblast-like cells and 40- to 50-nm-wide collagen fibrils that are arranged
      parallel to one another to form fibers approximately 1 micron in width. Collagen
      fibrils are composed of 10-nm-wide substructures that may run helically against
      the long axis of the fibril. Numerous rod-like structures ('rods') approximately
      10 nm in width are present around the collagen fibrils. Individual or groups of
      rods span spaces between neighboring collagen fibrils to interconnect them. The
      surfaces of the fibroblast-like cells are also connected to the nearest collagen
      fibrils through the rods. In place, strands with a thickness similar to that of
      the rods were seen self-assembled into irregular meshwork structures. The
      treatment of the tissue with 10% sodium hydroxide for up to 5 days removed most
      of these rods and strands, thus exposing a three-dimensional arrangement of
      collagen fibrils that is often not fully visualized in untreated tissues. With
      histochemical staining of thinly sectioned tissues using Alcian blue, these rods
      and strands were positively stained, and thus they were demonstrated to be
      composed of proteoglycans. The ultrastructural arrangement of the periodontal
      ligament, observed in this study as a delicate interaction of collagen and
      proteoglycan components, is likely to play a significant role in the transmission
      of occlusal forces applied to the tissue and in the dissipation of mechanical
      shock.

PMID- 9259879
TI  - Influence of spaceflight on succinate dehydrogenase activity and soma size of rat
      ventral horn neurons.
AB  - Succinate dehydrogenase (SDH) activities and soma cross-sectional areas (CSA) of
      neurons in the dorsolateral region of the ventral horn at the L5 segmental level
      of the spinal cord in the rat were determined after 14 days of spaceflight and
      after 9 days of recovery on earth. The results were compared to those in age
      matched ground-based control rats. Spinal cords were quick-frozen, and the SDH
      activity and CSA of a sample of neurons with a visible nucleus were determined
      using a digitizer and a computer-assisted image analysis system. An inverse
      relationship between CSA and SDH activity of neurons was observed in all groups
      of rats. No change in mean CSA or mean SDH activity or in the size distribution
      of neurons was observed following spaceflight or recovery. However, there was a
      selective decrease in the SDH activity of neurons with soma CSA between 500 and
      800 microns2 in the flight rats, and this effect persisted for at least 9 days
      following return to 1 g. It remains to be determined whether the selected
      population of motoneurons or the specific motor pools affected by spaceflight may
      be restricted to specific muscles.

PMID- 9259880
TI  - Scanning electron microscopy of the human zonule of the lens (Zonula ciliaris).
AB  - In the present study eight human eyeballs were specifically prepared for scanning
      electron-microscopic observation of the zonule. The zonule consisted of two main
      layers of radial fibres, an anterior and a posterior one, that inserted on the
      anterior and the posterior lens capsules, respectively. Some fibres inserted on
      the equator of the lens. Posterior zonular fibres originated at the pars plana,
      entered the dorsal part of the ciliary valleys and then changed their direction
      towards the posterior face of the lens. Posterior fibres inserted on the
      posterior capsule of the lens by branched endings 1 mm behind the equator of the
      lens. Anterior zonular fibres originated mainly at the pars plana and
      occasionally at the ciliary valleys. After running completely through the ciliary
      valleys in close contact with the lateral walls of the ciliary processes, they
      changed their direction at the anterior endings of the pars plicata and reached
      the anterior lens capsule. Anterior zonular insertions were achieved by webbed
      endings that diffused into the anterior capsule 2 mm in front of the lens
      equator. The extraordinary distension capacity of the zonular fibres was
      demonstrated by pulling the anterior lens capsule after hydrodissection. As a
      consequence, the anterior fibres were stretched up to four times their original
      length without breaking or disinserting.

PMID- 9259881
TI  - Structure, strain and function of the transverse acetabular ligament.
AB  - To assess the morphology and function of the transverse acetabular ligament
      (TAL), its internal structure and insertion sites were analyzed, and its strain
      was determined during hip joint loading. Fifteen specimens were embedded in
      methyl methacrylate and cut into 500-micron sections parallel to the inlet of the
      acetabulum. Polarized light microscopy and contact radiography revealed important
      differences between the ventral and dorsal attachment of the TAL. Ventrally, the
      fibers insert close to the labrum, at a rather extensive site consisting of
      fibrous cartilage. Dorsally, the ligament arises from a wide attachment at the
      bony region of the posterior horn, where it is continuous with the periosteum and
      the joint capsule. In a second part of the study, six specimens (four fixed, two
      fresh) were investigated, using a testing machine to simulate hip joint loading.
      The strains of the TAL and of two sites of the acetabular labrum were measured
      with strain gauges. Loads of 10-2,800 N were applied and the degree of rotation
      of the femoral head was varied. At 400% body weight, the TAL encountered tensile
      strains of up to 3.7%, but the labrum only of up to 0.5%. The contact areas of
      the hip joints were determined with a polyether casting material. At 50% body
      weight they were found to lie in the anterior and posterior aspects of the lunate
      surface. These results indicate that, due to a natural incongruity, the
      acetabular notch is widened during loading and the TAL submitted to tension.

PMID- 9259882
TI  - Hair distribution on the phalanges of the hand among Kanuris and Baburs/Buras of
      north-eastern Nigeria.
AB  - One thousand four hundred and seven Kanuri and Babur/Bura subjects of north
      eastern Nigeria were selected randomly in order to determine the frequency and
      distribution patterns of midphalangeal hair of their hands. Of these, 25.2%
      possessed hair on the middle phalanges (approximately 26% of males and 24% of
      females). Therefore, the sex difference was not statistically significant (p <
      0.2704). There was, however, a significant effect of age (p < 0.05), by which the
      incidence increased to a peak in the 10- to 15-year age group and, thereafter,
      decreased gradually to a maximum age of 35 years. The frequency order of
      occurrence of midphalangeal hair was 4 > 3 > 5 > 2. Eight patterns of hair
      distribution were found, but no subject had exclusive presence of hair on the
      middle phalanx of the index finger. The 3, 4, 5 finger combination was the most
      frequent. Hair on the proximal phalanx was absent in 8% of males and 7.6% of
      females. There was an ulnar rather than a radial shift in the distribution of
      midphalangeal hair, a phenomenon which might have been due to a shift in the
      morphogenetic gradient during development.

PMID- 9259883
TI  - The cricothyroid space: topography and clinical implications.
AB  - The inferior border of the thyroid cartilage and the superior rim of the cricoid
      arch are connected by the cricothyroid membrane and partly covered by the
      cricothyroid muscles ventrally. This region has been termed the cricothyroid
      space (CS) and is important with regard to surgical procedures, the spread of
      laryngeal cancer and traumatic lesions of the larynx. The precise topographic
      relations of the CS were investigated in plastinated serial sections of 21 normal
      adult human specimens. The CS consists of a caudal and a cranial portion, which
      are different with regard to their cartilaginous framework and their relationship
      to intralaryngeal structures. The caudal portion is bordered by the cricoid
      cartilage and reveals a complete separation of extra- and intralaryngeal regions
      by the cricothyroid membrane. It provides an easy access to the subglottic
      airways. The cranial portion of the CS is mainly bordered by the thyroid
      cartilage. It is characterized by a gap lateral to the median cricothyroid
      ligament. This allows a connection of extra- and intralaryngeal adipose tissue.
      There, extralaryngeal extension of laryngeal cancer preferentially occurs.
      Traumatic subglottic ruptures of the larynx involve both the caudal and cranial
      portions of the CS, which often results in extensive scar tissue formation.

PMID- 9259884
TI  - The importance of operational factors for the interpretation of indicators in the
      Hansen's disease endemic in Brazil.
AB  - In Brazil, an increase has been recorded in recent years in the magnitude of
      detection coefficients for new cases of Hansen's disease, which is frequently
      interpreted as evidence of the endemic's expansion. The objective of this work is
      the determine the role of operational factors for interpreting the trend
      displayed by the morbidity coefficients for Hansen's disease from 1982 to 1995 in
      the country. We observed a strong correlation between the adjusted detection
      coefficients and the number of technicians trained (r = 0.80), a decrease in the
      proportion of new cases with disabilities at the time of diagnosis (r = 0.86),
      and a downward trend in tuberculoid forms (r = -0.70). Patient time on the active
      register is correlated negatively with MDT-WHO coverage (r = -0.95) and the
      percentage of patients discharged from treatment due to cure (r = -0.91). These
      results suggest that the increase in the potential for detection of new cases of
      Hansen's disease resulting from new strategies adopted by the program, i.e.,
      mainly extensive training of health personnel, could be a coherent explanation
      for the increase in detection coefficients for new cases observed in Brazil in
      the last ten years.

PMID- 9259885
TI  - Rifampicin and isoniazid in the treatment of leprous nerve abscesses.
AB  - Thirty nine cases of borderline tuberculoid leprosy having nerve abscesses (15
      with sinuses) were treated with daily dose of rifampicin and isoniazid for six
      months along with standard multidrug therapy. The patients were followed up for
      three to five years. No recurrence of abscess or sinus was observed. Observations
      indicate that medical approach is required at times to supplement surgical
      intervention for management of these cases.

PMID- 9259886
TI  - Prevalence of HIV1 in leprosy patients in Rio de Janeiro, Brazil.
AB  - The purpose of this study was to learn if HIV1 infection was associated with
      leprosy in Rio de Janeiro, Brazil by comparing the prevalence rates of 1.016
      leprosy patients tested on a voluntary basis and 78.482 blood donors. A cross
      sectional survey of anti-HIV1 antibodies was conducted in Rio de Janeiro, from
      1990 to 1992 for this purpose. HIV1 prevalence found among leprosy patients was
      (3 cases) 2.9 per 1000, and among blood donors was (282 cases) 3.8 per 1000. Such
      difference was not significant (OR = 0.79; p = 0.69). Since HIV1 cases were only
      found among male leprosy patients, further analysis excluded females. Male
      leprosy patients showed a slightly higher prevalence of HIV1 than blood donors
      before and after age adjustment. However, this result was not statistically
      significant (adjusted odds ratio = 1.38, 95% CI 0.35-4.5; p = 0.83). These data
      do not provide evidence that leprosy and HIV1 infection are associated in the
      State of Rio de Janeiro. This is consistent with similar investigations conducted
      elsewhere.

PMID- 9259887
TI  - Changes in size of the functional cyst on ultrasonography during early pregnancy.
AB  - To clearly define the clinical behaviors of the functional cyst by
      ultrasonography and distinguish this cyst from other sonolucent ovarian cysts in
      pregnancy, changes in functional cyst size during early pregnancy were
      retrospectively evaluated with the cyst diameters derived from ultrasonic records
      of 58 pregnant patients with functional cysts. Of the 58 cases, 7 cases of
      functional cysts over 6 cm in diameter and 5 cases after 15 weeks were observed.
      Percent changes in cyst size per weeks of gestation were calculated from
      diameters of all cases. These percent changes were averaged respectively in four
      chronologic groups (5-7, 7-9, 9-12, and 12-15 weeks of gestation). As a result,
      although the mean percent change in cyst size showed a tendency to increase from
      5 to 7 weeks (+0.9% per week), it turned negative after 7 weeks, and the
      decreasing tendency grew as gestation advanced (7-9 weeks: -8.3% per weeks; 9-12
      weeks: -11.7% per weeks; 12-15 weeks: -15.2% per week). Therefore, the result
      showed that the maximum cyst size is reached at about 7 weeks with gradual
      diminution thereafter and the sonolucent ovarian cyst may be followed as a
      functional cyst, even if it is large or persists after 14 weeks.

PMID- 9259888
TI  - Is maternal thyrotropin releasing hormone administration safe in the pregnant
      woman with preeclampsia?
AB  - Maternal intravenous administration of thyrotropin releasing hormone (TRH) is
      associated with rapid elevations of blood pressure potentially causative of
      cerebrovascular accidents. We report a case in which peak blood pressure of
      220/120 mm Hg was attained from a baseline of 132/80 mm Hg following TRH
      administration in a preeclamptic patient.

PMID- 9259889
TI  - Time quantified detection of fetal movements using a new fetal movement
      algorithm.
AB  - Primarily, the objective is to develop an automated ultrasound fetal movement
      detection system that will better characterize fetal movements. Secondarily, the
      objective is to develop an improved method of quantifying the performance of
      fetal movement detectors. We recorded 20-minute segments of fetal movement on 101
      patients using a UAMS-developed fetal movement detection algorithm (Russell
      algorithm) and compared this to a Hewlett-Packard (HP) M-1350-A. Movements were
      recorded on a second-per-second basis by an expert examiner reviewing videotaped
      real-time ultrasound images. Videotape (86,592 seconds) was scored and compared
      with the electronic movement-detection systems. The Russell algorithm detected
      95.53% of the discrete movements greater than 5 seconds, while the HP system (M
      1350-A) detected only 86.08% of the discrete movements (p = 0.012). Both devices
      were less efficient at detecting the short discrete movements, obtaining
      sensitivities of 57.39 and 35.22, respectively. Neither system fully identifies
      fetal movement based on the second-per-second system. Improved methods of
      quantifying performance indicated that the Russell algorithm performed better
      than the HP on these patients.

PMID- 9259890
TI  - Color Doppler aided prenatal diagnosis of a type 1 cystic sacrococcygeal teratoma
      simulating a meningomyelocele.
AB  - Type 1 cystic sacrococcygeal teratomas, usually associated with good outcome
      following neonatal resection, must be differentiated at the time of prenatal
      diagnosis from sonographically similar meningomyeloceles, which carry a grave
      prognosis. We present an unusual case in which color Doppler imaging assisted
      correct midtrimester prenatal diagnosis of a large type 1 cystic sacrococcygeal
      teratoma closely simulating a meningomyelocele.

PMID- 9259891
TI  - Preeclampsia and preterm birth subtypes in Nova Scotia, 1986 to 1992.
AB  - The goal of this study was to evaluate the influence of preeclampsia on preterm
      delivery, examining whether the association varied among preterm birth subtypes
      defined by gestational age and precipitating events. A population-based,
      longitudinal study of the association between mild and severe preeclampsia and
      preterm birth subtypes was conducted among 59,851 women (resulting in a total of
      78,086 pregnancies) delivering singleton live births in the province of Nova
      Scotia, Canada between 1986 and 1992, utilizing the Nova Scotia Atlee perinatal
      database. Very preterm (< 33 weeks' gestation) and moderately preterm (33-36
      weeks' gestation) births were further classified as occurring due to (1) membrane
      rupture, (2) medical intervention, and (3) spontaneous onset of labor (before
      membrane rupture). Mild and severe preeclampsia occurred in 8.7 and 1.7% of
      pregnancies, respectively, after exclusions of multiple births. After adjustment
      for confounders by multivariable logistic regression based on the generalized
      estimating equations, severe preeclampsia was strongly associated with the risk
      of very preterm birth (RR = 80.8, 95% CI: 54.2-120.6), and moderately preterm
      birth (RR = 41.8, 95% CI: 34.0-51.4) due to medical intervention. A less
      dramatically elevated risk of very preterm (RR = 2.1, 95% CI: 1.1-4.0) and
      moderately preterm (RR = 2.2, 95% CI: 1.7-2.9) birth due to medical intervention
      was apparent among pregnancies complicated by mild preeclampsia. Very preterm
      births due to membrane rupture were too rare to examine, but moderately preterm
      births due to membrane rupture were not associated with preeclampsia.
      Preeclampsia was associated with an increase in the risk of moderately preterm
      births due to spontaneous labor (RR = 1.9, 95% CI: 1.3-2.8), but not very preterm
      births (RR = 1.0, 95% CI: 0.7-1.2). Substantial variability was observed in the
      association between preeclampsia and preterm birth in relation to the subtypes
      defined by gestational age and pathway, with strong associations between
      hypertension and medically induced preterm births. The results indicate a need to
      separate preterm births into subcategories to properly evaluate the association
      between preeclampsia and preterm births and interventions to reduce the adverse
      effects of preeclampsia.

PMID- 9259892
TI  - Experience with treatment of three pairs of conjoined twins.
AB  - Three pairs of female conjoined twins--a xiphoomphalopagus, a pygopagus, and a
      thoracopagus--were encountered during the past 10 years. Surgical separation was
      successful in the xiphopagus, and both twins survived. Separation was also
      successful in the pygopagus, but only one of the twins survived; the twin that
      died had sustained cerebral hemorrhage before the operation. Both of the twins in
      the thoracopagus died before surgery could be performed, due to sepsis and heart
      failure, 44 days after birth. Separation surgery of conjoined twins is often
      successful with a high survival rate of both twins unless vital organs such as
      the brain or the heart are fused. However, unlike other operations, separation
      surgery entails ethical considerations pertaining to matters such as the
      distribution of organs in addition to surgical considerations. Furthermore,
      separation of conjoined twins is certain to cause various degrees of anatomical
      as well as functional disorders associated with the surgical procedure, and
      provision for the postoperative care for these disorders is indispensable.

PMID- 9259893
TI  - First report of distal obstructive uropathy and prune-belly syndrome in an infant
      with amniotic band syndrome.
AB  - We describe the first report of distal obstructive uropathy and prune-belly
      syndrome in an infant with amniotic band syndrome. Prenatal ultrasonographic
      examination in the third trimester revealed intermittent oligohydramnios,
      bilateral hydronephrosis, and megacystis. Postnatally, the infant was found to
      have a scalp defect, a skin pedicle, pseudosyndactyly and constriction rings on
      the hands, marked distention of the abdomen, a fibrous band attached to the
      proximal urethra causing urethral stricture, a swollen penile shaft, bilateral
      talipes equinovarus, and syndactyly of the feet. Multiple fibrous amniotic bands
      could be identified in the placenta. Our case shows that fetal distal obstructive
      uropathy can be associated with the congenital constriction band syndrome.

PMID- 9259894
TI  - Increased incidence of fetal growth restriction in association with breech
      presentation in preterm deliveries < 32 weeks.
AB  - Breech presentation and fetal growth restriction (FGR) are each related
      independently with preterm delivery. This study was designed to assess the
      possible relationship between breech presentation and FGR in deliveries at < 32
      weeks' gestation. From an established database of 465 consecutive deliveries at <
      32 weeks of nonhypertensive, nondiabetic patients with singleton nonanomalous
      fetuses, those in whom birth weight, body length, fetal presentation (vertex or
      breech), and amniotic fluid volume (AFV) had been assessed were studied. Fetal
      growth restriction (defined as symmetric if both birth weight and body length
      were < 10th percentile and asymmetric if only the birth weight was < 10th
      percentile) was studied in relation to maternal age, parity, tobacco use, fetal
      presentation, AFV, membrane status, and gestational age at delivery. Statistical
      analyses included contingency tables and analysis of variance, with p < 0.05
      considered significant. Two hundred ninety-eight patients met the inclusion
      criteria. In these patients 85 (28.5%) fetuses were breech and 213 (71.5%)
      cephalic. A total of 56 (19%) fetuses were growth restricted. Of these, 31
      (10.4%) were symmetrically and 25 (8.3%) asymmetrically growth restricted. The
      incidence of symmetric growth restriction in the breech-presenting fetuses was
      16% (n = 14) versus 8% (n = 17) in the cephalic-presenting fetuses, and of
      asymmetric growth restriction 12% (n = 10) versus 7% (n = 15), (overall p =
      0.03). Fetal growth restriction was not associated with significant differences
      in maternal age, parity, smoking, AFV, membrane status, or gestational age at
      delivery (each p > 0.10). In preterm deliveries at < 32 weeks' gestation, breech
      presentation is associated with an increased incidence of intrauterine growth
      restriction, independent of clinical confounders.

PMID- 9259895
TI  - Remote umbilical arterial blood pH analysis: accuracy, utility, and limitations.
AB  - It is not always possible or feasible to perform routine umbilical artery blood
      sampling at birth. This study was undertaken to assess the accuracy of selective
      remote umbilical arterial blood analysis to retrospectively predict the original
      birth pH of any newborn. Umbilical arterial blood samples were obtained in two
      preheparinized syringes immediately following 1007 deliveries. One sample was
      analyzed within 60 minutes of delivery. The other was placed on ice and later
      analyzed at variable time intervals up to 180 hours postpartum. The results of
      each remote analysis were adjusted using a previously published regression
      equation to accurately identify which newborns had pH values < 7.00, < or = 7.10,
      or < 7.20 at birth. Among the 1007 newborns, there were 14 (1.3%), 44 (4.3%), and
      187 (18.5%) who had pH values < 7.00, < or = 7.10, and < 7.20, respectively, at
      birth. Remote umbilical arterial samples analyzed within 72 hours of delivery
      correctly identified newborns with an original pH < 7.00, < or = 7.10, or < 7.20
      with: (1) a sensitivity of 100, 82, and 84%, respectively; (2) positive
      predictive values of 100, 93, and 66%, respectively; and (3) a test efficiency of
      100, 99, and 89%, respectively. Up to 72 hours after delivery, remote umbilical
      arterial blood pH analysis can be reliably used to accurately identify the
      newborn that was acidotic at birth.

PMID- 9259896
TI  - Effects of theophylline on renal function in premature infants.
AB  - Xanthines are frequently being used in the management of premature babies.
      Studies in adult subjects have demonstrated a diuretic effect of aminophylline
      due to the inhibition of solute reabsorption in various segments of the nephron.
      We evaluated the effects of aminophylline on the developing kidney. Nineteen
      premature infants, with a mean +/- SD gestational age of 31.1 +/- 2.8 weeks and
      mean birth weight of 1481 +/- 454 g were studied at mean age of 4.5 +/- 4.0 days
      before and after a 20-minute loading infusion of 6 mg/kg aminophylline, followed
      by maintenance therapy at a dose of 2 mg/kg every 12 hours. A marked diuresis
      occurred immediately after the loading dose, the ratio of urinary output to water
      intake increased from 0.58 +/- 0.36 to 1.19 +/- 0.65. Concomitantly, the
      fractional excretion of sodium increased from 2.7 +/- 2.6% to 5.7 +/- 4.4% and
      that of potassium rose from 21 +/- 19% to 31 +/- 21%. Urinary calcium and uric
      acid excretion were also enhanced: calcium to creatinine ratio rose from 0.31 +/-
      0.29 to 0.60 +/- 0.54 and uric acid to creatinine ratio increased from 2.5 +/-
      1.5 to 3.8 +/- 2.0. Tubular reabsorption of phosphorus (TRP) was not affected.
      Most of the effects were no longer evident after 24 hours, despite continuing
      aminophylline maintenance therapy. In premature infants the aminophylline loading
      dose, but not maintenance therapy, affected renal functions. Because heart rate,
      blood pressure, and creatinine clearance did not change, it appears that
      aminophylline acts directly on tubular reabsorptive functions.

PMID- 9259897
TI  - Massive hemoptysis in pregnancy treated with bronchial artery embolization.
AB  - Massive hemoptysis is a life-threatening situation that rarely complicates
      pregnancy. Presented is a case of massive hemoptysis during pregnancy, which was
      successfully diagnosed and treated with bronchial artery angiogram and
      embolization. A 26-year-old multigravida at 19 weeks' gestational age with a
      history of intravenous substance abuse and infective endocarditis presented with
      hemoptysis. Extensive workup, including bronchoscopy, echocardiography, and
      magnetic resonance pulmonary angiography were negative. The patient left the
      hospital against medical advice to return 4 weeks later with massive hemoptysis.
      Bronchial arteriography revealed multiple areas of potential bleeding in the
      right and left lower lobes. Bilateral bronchial artery embolization was
      performed. The patient carried the pregnancy to term with no further episodes of
      hemoptysis. Hemoptysis during pregnancy requires a thorough workup and prompt
      treatment if the etiology is diagnosed. When faced with massive hemoptysis, the
      obstetrician should strongly consider bronchial artery angiography and
      embolization.

PMID- 9259898
TI  - Bartter's syndrome in pregnancy: a case report and review.
AB  - Bartter's syndrome is a rare autosomal recessive disorder characterized by
      hypokalemia, hyperaldosteronism, sodium wasting, normal blood pressure,
      hypochloremic alkalosis, and hyperplasia of the juxtaglomerular apparatus. We
      present a 21-year-old African-American nulliparous patient who was referred to
      our clinic at 9 weeks' gestation with a history of Bartter's syndrome. Her
      antenatal course was complicated by muscle cramps, which required increasing
      potassium supplementation. She developed hypomagnesemia in the third trimester of
      pregnancy, which necessitated magnesium therapy. She delivered an unaffected
      infant at term. Bartter's syndrome, although extremely rare in pregnancy,
      requires prompt recognition and careful management, as it may have significant
      maternal and neonatal implications.

PMID- 9259899
TI  - Fetal echocardiographic screening of diabetic pregnancies for congenital heart
      disease.
AB  - This study sought to assess pregnant diabetic women for the presence of fetal
      cardiac anomalies and to determine whether better diabetic control was associated
      with a reduced risk to the fetus. Between 1988 and 1995, pregnant type I and II
      diabetic women routinely underwent fetal echocardiography. Hemoglobin A1c values
      were used as an indicator of maternal diabetic control and any relation between
      congenital heart disease in the fetus and maternal hemoglobin A1c levels was
      sought. Cardiac defects were identified in 7 of 328 pregnancies assessed, for an
      incidence of congenital heart disease of 2.1% (95% confidence interval: 0.6
      3.6%). A review of the postnatal cardiac database did not reveal any undetected
      major malformations. The mean hemoglobin A1c level was 7.6% +/- 2.0% obtained at
      a mean gestational age of 12 +/- 7 weeks. Hemoglobin A1c levels of mothers
      carrying a fetus with congenital heart disease did not significantly differ from
      those with a normal fetus: 8.1% +/- 3.4% versus 7.6% +/- 1.9% (p = 0.48). Mothers
      with an affected fetus demonstrated a wide range of HbA1c levels (4.1 to 13.7%).
      Thus, the incidence of significant fetal cardiac abnormalities is low and not
      significantly related to maternal diabetic control.

PMID- 9259900
TI  - Unusual misplacement sites of percutaneous central venous lines in the very low
      birth weight neonate.
AB  - Percutaneously placed central venous lines have become an intricate part of the
      medical management of the very low birth weight infant. It is critically
      important that health care providers involved with the placement of these
      catheters be familiar with the possible subtle sites for catheter misplacement.
      We present two case reports of inadvertent ascending lumbar vein catheterization
      with a percutaneously placed Silastic catheter where the saphenous vein was used
      for venous access. The literature is reviewed with regard to the history of use,
      indications, placement, and associated complications of these catheters.

PMID- 9259901
TI  - Early prenatal diagnosis of hydrocephalus.
AB  - The aim of the present study was to assess the accuracy of various measurements
      of the lateral ventricles (LVs) for the early prenatal diagnosis of evolving
      congenital hydrocephalus. A prospective study was conducted among 61 normal
      pregnancies, and 20 pregnancies complicated by neural axis malformations, between
      19 and 24 weeks' gestation. The following ultrasound measurements were obtained:
      atrial width (AW); atrial-width/cerebro-atrial distance (CAD); left ventricular
      width/hemispheric distance, and cerebro-frontal horn/hemispheric width (HW)
      distance. Atrial width or AW/CAD had the highest diagnostic accuracy of 97.1%
      between 19-21 weeks; and 100% between 22-24 weeks. The other two parameters had
      improved accuracy as gestational age increased. However, between 19-21 weeks the
      other parameters were below 90% in their diagnostic accuracy. These data
      demonstrate that the simple measurement of the AW, used either singly or as a
      ratio with the CAD is effective for the early prenatal diagnosis of evolving
      hydrocephalus.

PMID- 9259902
TI  - Morbidity in the preterm infant with mature lung indices.
AB  - This study was designed to evaluate neonatal morbidity and mortality following
      preterm delivery in the setting of mature amniotic fluid pulmonary studies. We
      performed a retrospective analysis of all pregnancies resulting in preterm
      deliveries (< 37 weeks) from 1/1/88 to 5/31/92 in which there was a "mature"
      phospholipid profile, defined as positive phosphatidylglycerol (PG) or
      lecithin/sphyngomyelin (L/S) ratio > or = 2 determined within 1 week of delivery.
      Excluded were multiple gestations, diabetic pregnancies, and fetal or neonatal
      abnormalities involving the cardiovascular, renal, or pulmonary tract. Main
      outcome measures were incidence of significant neonatal morbidity, including
      respiratory distress requiring respiratory support, sepsis, patent ductus
      arteriosus, grade 3-4 intraventricular hemorrhage, necrotizing enterocolitis,
      retinopathy of prematurity, meningitis, and pneumonia. A total of 153 patients
      fulfilled the inclusion criteria. Mean (SD) gestational age at delivery and birth
      weight were 33.8 (2.1) weeks and 2298 (561) g, respectively. There were no
      neonatal deaths, but significant morbidity was present in 20% (31/153) of cases.
      The most common major neonatal complications were respiratory distress (12%) and
      suspected or documented sepsis (16%). Univariate analysis showed that frequency
      of major neonatal morbidity was related to gestational age at delivery (p <
      0.001), birth weight (p < 0.001), Apgar score at 5 minutes < 7 (p = 0.008) and
      method of lung maturity assessment (complications were ore frequent when lung
      maturity was defined by L/S > or = 2 than by PG positivity) (p = 0.02).
      Multivariate analysis demonstrated a significant association between the presence
      of a neonatal complication and method of lung maturity assessment after
      adjustment for gestational age at delivery (p = 0.04). The incidence of major
      neonatal complications among preterm infants is high even in the presence of
      mature fetal lung studies; this incidence is related primarily to the gestational
      age at birth, and secondarily to the method of lung maturity testing
      (complications are less common in the presence of PG positivity than of L/S > or
      = 2).

PMID- 9259903
TI  - A case of neonatal choriocarcinoma.
AB  - Choriocarcinoma occurring in a placenta and metastasizing to the fetus is quite
      rare. We describe here a case of such infantile choriocarcinoma, initially
      appeared as refractory anemia and rapidly metastasized to the liver, lungs, and
      brain. The placenta looked normal and was not submitted to histological
      examinations. Neither noninvasive nor invasive diagnostic methods
      (ultrasonography, computed tomography, magnetic resonance image, scintigraphy,
      and hepatic arteriography) gave any diagnostic information on the tumor. Liver
      biopsy was considered too risky due to a possible bleeding. Correct diagnosis was
      established only after the postmortem examination. Two months after the infant's
      death, we were informed that the mother was found having hepatic and pulmonary
      tumors. The importance of the maternal history and measurement of urinary human
      chorionic gonadotropin is emphasized for a rapid and correct diagnosis of
      infantile choriocarcinoma.

PMID- 9259904
TI  - Increased intrapartum antibiotic administration associated with epidural
      analgesia in labor.
AB  - To determine whether women who receive continuous epidural analgesia for labor
      and delivery are more likely to receive antibiotic therapy compared to those
      parturients who do not use epidural analgesia, a chart review was performed for
      300 women 100 in each group using narcotics alone epidural alone, or parenteral
      narcotics followed by epidural analgesia. While only 2% of women with narcotics
      alone developed an intrapartum temperature > or = 37.8 degrees C, 16% and 24% of
      women with epidural use alone or in addition to narcotics did so, respectively.
      Antibiotic administration was increased among women utilizing epidural analgesia,
      exclusively or following parenteral narcotics. No parturient with culture or
      pathological evidence of chorioamnionitis had maternal temperature elevation as
      an isolated finding. A probable causal relationship between maternal temperature
      elevation and epidural use in labor is supported. Rather than treating all women
      with temperature elevations and epidurals for presumed chorioamnionitis, it is
      reasonable to target treatment to those with fetal tachycardia, meconium stained
      fluid, or abnormal amniotic fluid studies.

PMID- 9259906
TI  - Perinatal myocardial infarction in a newborn with a structurally normal heart.
AB  - Myocardial infarction in a newborn infant in the absence of congenital heart
      disease and anomalous coronary artery anatomy is extremely rare. We report a case
      of a newborn with a structurally normal heart who presented shortly after birth
      with congestive heart failure and cardiovascular collapse suggestive of a
      hypoplastic left ventricle or critical aortic stenosis. This newborn had a
      massive myocardial infarction caused by thromboembolic occlusion of the left main
      coronary artery. Clinical, laboratory, and autopsy data suggest the event
      occurred in utero.

PMID- 9259905
TI  - A placebo-controlled randomized trial of the terbutaline pump for prevention of
      preterm delivery.
AB  - To determine the efficacy of the terbutaline pump for the prevention of preterm
      delivery, patients in preterm labor defined by progressive cervical change
      underwent intravenous magnesium sulfate tocolysis (with or without oral
      indomethacin, as necessary), and once labor was arrested, were randomized to one
      of three treatment arms: terbutaline by pump, saline by pump (blinded), or oral
      terbutaline. If recurrent preterm labor occurred despite maximization of therapy,
      the treatment arm was determined and therapy was changed; saline pump and oral
      terbutaline were switched to terbutaline pump, terbutaline pump was switched to
      oral terbutaline. Patients who continued to labor were readmitted for aggressive
      intravenous therapy. Women randomized to the terbutaline pump (n = 15), saline
      pump (n = 12), and oral terbutaline (n = 15) groups were similar in terms of
      gravidity, parity, days of tocolysis before study entry, gestational age at
      entry, and cervical dilatation at entry. The mean gestational age at delivery was
      the same in all three groups (35 weeks), as were neonatal outcomes. Terbutaline
      by pump, saline by pump, and oral terbutaline appear equivalent for the
      prevention of preterm delivery. The terbutaline pump should remain experimental.

PMID- 9259907
TI  - Ehlers-Danlos syndrome type II in pregnancy.
AB  - Ehlers-Danlos syndrome type II is a rare connective tissue disorder with unknown
      pregnancy-related maternal and fetal morbidity. The course and outcome of
      pregnancy in a primigravid woman with Ehlers-Danlos syndrome type II is
      described. At 17 weeks' gestation a prophylactic Shirodkar cerclage was performed
      without complications. From the 29th week on, decreased blood flow of the
      umbilical artery was measured, and fetal growth retardation was evident from 34
      weeks' gestation on. Pregnancy ended at 41 weeks by spontaneous vaginal delivery
      of a healthy 2900-g female infant. Previous reports of 16 women with Ehlers
      Danlos syndrome type II, who had a total of 24 pregnancies, are reviewed.

PMID- 9259908
TI  - A pilot study identifying type V collagenolytic activity in human amniotic fluid.
AB  - Amniorrhexis complicates pregnancies if it occurs in a preterm pregnancy or
      remote from the onset of labor in a term pregnancy. There are different collagen
      types (I-V) that create the extracellular matrix of the amnion. Collagenases
      specific to these collagen types, with the exception of type V collagen, are
      found in human amniotic fluid, fibroblasts, polymorphonuclear leukocytes and
      bacteria. Type V collagen is a major component of the amniotic basement membrane
      and is responsible for maintaining a barrier to bacteria and to the loss of
      amniotic fluid. We sought to find evidence of type V collagenolytic activity in
      human amniotic fluid obtained from pregnancies in different clinical states.

PMID- 9259909
TI  - Fatal hepatic veno-occlusive disease in a newborn infant.
AB  - We describe a newborn infant with veno-occlusive disease (VOD) of the liver.
      Prior to discharge from the hospital, the newborn, who had been treated for
      suspected neonatal infection, suddenly developed sepsis-like symptoms. The size
      of the liver as well as serum activity of hepatic enzymes increased
      progressively. Initial Doppler-flow studies demonstrated an absent flow in the
      vena portae, a finding that was compatible with vena portae thrombosis or
      occlusion of other hepatic veins. A therapy with recombinant tissue plasminogen
      activator (rt-PA) was initiated; due to extensive bleedings from various sides,
      the fibrinolytic therapy had to be withdrawn 12 hours later, when Doppler-flow
      examination revealed a reverse flow in hepatofugal direction. Despite supportive
      therapy, the general condition of the patient deteriorated continuously, finally
      resulting in liver and renal failure. Our patient died 19 days after birth. The
      autopsy demonstrated obliterative lesions of the centrilobular and sublobular
      hepatic veins, the classical signs of VOD of the liver. Despite extensive
      diagnostics and examinations, the etiology of VOD could not been elucidated in
      this newborn.

PMID- 9259910
TI  - Trichosporon beigelii, a new neonatal pathogen.
AB  - Trichosporon beigelii is an uncommon cause of sepsis in low-birth-weight infants.
      We present two cases of neonatal trichosporonosis and two cases of neonatal
      trichosporon colonization to familiarize neonatologists with this entity and to
      discuss management considerations. A 23-week-gestation male developed clinical
      evidence of sepsis on day 10 and was found to have "yeast" growing in a blood
      culture on day 12. Despite receiving amphotericin B, he expired within 2 days, at
      which time the organism was identified as T. beigelii. A 23-week gestation female
      developed fungal septicemia in the second week of life, while being treated for
      persistent bacterial sepsis. Candida albicans grew from blood culture, while T.
      beigelii grew from suprapubic urine, tracheal aspirate, and umbilical catheter
      tip cultures. She died 2 days later despite therapy with amphotericin B, at which
      time the fungal isolates were correctly identified. Two other infants were found
      to have colonization of central vascular catheters, without evidence of invasive
      disease. Trichosporon infections in neonates have been almost uniformly fatal.
      Most strains of T. beigelii are relatively resistant to amphotericin B and may be
      confused with Candida sp. on initial culture examinations. Therefore, delays in
      appropriate treatment may occur. We discuss treatment options, including
      alternative antifungal drugs, as well as possibilities for combination therapy.

PMID- 9259911
TI  - Pregnancy outcome following first trimester exposure to antihistamines: meta
      analysis.
AB  - To determine the relative risk for major malformations associated with
      antihistamine (H1 blockers) exposure in the first trimester of pregnancy, a
      literature search of all studies examining the association between antihistamines
      and major malformations for the period 1960 to 1991 was conducted, followed by
      meta-analysis. Odds ratio was calculated using the Mantel-Haenszel method. Twenty
      four controlled studies met the inclusion criteria with more than 200,000
      participating women. The summary odds ratio of major malformations associated
      with antihistamines taken during the first trimester was 0.76 (95% CI: 0.60
      0.94). This analysis indicates that H1 blockers used mainly for morning sickness
      during the first trimester do not increase the teratogenic risk in humans and
      may, in fact, be associated with a protective effect. More study is needed to
      verify the possibility that by preventing vomiting, antihistamines may ensure
      better metabolic conditions to the fetus and thus may reduce some birth defects.
      Alternatively, it is possible that pregnancies characterized by vomiting are
      associated with better outcome due to other reasons, such as hormonal status or
      placental function. Women suffering from morning sickness which is not controlled
      by nonpharmacological methods can safely use antihistamines.

PMID- 9259912
TI  - Residual amniotic fluid volume in preterm rupture of membranes: association with
      fetal presentation and incidence of clinical and histologic evidence of
      infection.
AB  - The objective of this study was assess whether residual amniotic fluid volume
      (AFV) following premature rupture of the membranes (PROM) is associated with
      fetal presentation, or the prevalence of either clinical or histologic infection
      in patients delivering below 32 weeks' gestation. From an established database of
      465 deliveries below 32 weeks' gestation, patients with singleton, nonanomalous
      fetuses with AFV assessment within 24 hours of delivery were studied (n = 146).
      Fetal presentation was confirmed by ultrasound identifying 46 breech and 100
      vertex-presenting fetuses. Premature rupture of the membranes was diagnosed by
      sterile speculum examination. Clinical chorioamnionitis was diagnosed by
      previously published criteria. Histopathology examination of the extraplacental
      amnion and the umbilical cord were performed by a single pathologist blinded to
      clinical data. Outcome variables evaluated: rupture-to-delivery interval,
      gestational age at delivery, neonatal morbidity parameters (1- and 5-min Apgar
      scores < 5 and 7, respectively; incidence of respiratory distress syndrome;
      bronchopulmonary dysplasia; retinopathy of prematurity; neonatal sepsis;
      intraventricular hemorrhage; days of ventilation; and hospitalization), and
      placental histologic parameters of maternal and/or fetal acute inflammation.
      Statistical analysis included contingency tables and analysis of variance with p
      < .05 considered significant, after corrections for multiple comparisons when
      appropriate. Residual AF volume following PROM was significantly lower in breech
      compared with vertex presentation (AFV = 0 in 20 vs. 34; AFV = 1 in 19 vs. 27;
      AFV = 2 in 7 vs. 39, respectively, p = .014). No significant difference was noted
      in the rupture-to-delivery interval, gestational age at delivery, neonatal
      morbidity parameters, or histologic evidence of maternal and/or fetal acute
      inflammation (50% vs. 42%, p > .2) between gestations with breech or vertex
      presentations. The incidence of clinical chorioamnionitis was significantly lower
      in breech compared with vertex presentation (40% vs. 60%, p < .05). We conclude
      that following PROM below 32 weeks' gestation, in breech-presenting fetuses, the
      residual AFV and incidence of clinical chorioamnionitis are significantly
      decreased compared with vertex-presenting fetuses.

PMID- 9259913
TI  - Influence of gestational age on the time from spontaneous rupture of the
      chorioamniotic membranes to the onset of labor.
AB  - Our goal was to assess the influence of gestational age on the timing of labor
      onset following spontaneous rupture of the chorioamniotic membranes. The 24,831
      patients in the Nova Scotia Atlee perinatal database from 1986 to 1992 whose
      membranes ruptured prior to labor onset and had live births were analyzed using
      life-table analysis methods. The probability of labor onset at specified
      intervals following rupture was markedly lower when rupture occurred earlier in
      gestation. Pregnancies of < 33 weeks' gestation were less than half as likely as
      term pregnancies to proceed to labor within 24 hours and pregnancies of 33-36
      weeks' gestation were 50-75% as likely as term pregnancies to progress within
      that period. These data provide clear evidence that the earlier in gestation the
      rupture occurs, the less likely labor onset is within specified time periods.
      This pattern supports the contention that preterm rupture of membranes is
      etiologically distinct from preterm labor.

PMID- 9259914
TI  - Pregnancies in a patient with congenital absence of prothrombin activity: case
      report.
AB  - Congenital hypoprothrombinemias are very rare, inherited disorders in which
      factor II (prothrombin) levels and/or activity are extremely low or absent. We
      report eight pregnancies in a patient with this disorder. Obstetric complications
      attributed to the coagulation disturbance included first-trimester bleeding in
      each pregnancy, miscarriage in four of the pregnancies, spontaneous maternal
      subarachnoid hemorrhage in one, and postpartum hemorrhage in one of four term
      pregnancies despite administration of clotting factor concentrate. The management
      of pregnancy in congenital hypoprothrombinemia, and issues of coagulation factor
      replacement, are discussed.

PMID- 9259915
TI  - Doppler velocimetry and nonstress test for predicting outcome of pregnancies with
      decreased fetal movements.
AB  - Because fetal motor activity reflects the fetal condition in utero, maternal
      counting of fetal movements has been suggested as a useful method for monitoring
      fetal well-being, based on empirical evidence that a decrease in or absence of
      fetal movements often presages fetal death. The aim of this study was to compare
      the predictive capacity of umbilical artery (UA) Doppler velocimetry with that of
      nonstress test (NST) cardiotocography in 599 women with low-risk pregnancies,
      reporting decreased fetal movements. In 19 cases the fetus was dead on maternal
      admission. Umbilical artery Doppler velocimetry and NST were performed in the
      remaining 580. In 541 the NST and UA velocimetry findings were reassuring, and
      the women were discharged. There was one perinatal death in this group, due to
      extreme prematurity and placental abruption 1 week later. Thirty-nine women who
      gave birth on the day of admission or next day were especially given closer
      attention. Umbilical artery velocimetry was abnormal in only one fetus. In 6
      cases, the NST trace on admission indicated fetal distress, and emergency
      cesarean section was performed, resulting in 3 infant deaths and 3 infants with
      sequelae. The umbilical cord pH was normal in 3, suggesting an earlier temporary
      intrauterine hypoxic event. Overall perinatal mortality was thus 23 (3.8%).
      Decreased fetal movement perception by mothers should therefore be taken
      seriously, even though an irreversible insult to the fetus might already have
      occurred.

PMID- 9259916
TI  - Clinical impact of peritoneal equilibration testing in treatment of congenital
      lactic acidosis by acute peritoneal dialysis.
AB  - Although peritoneal equilibration testing (PET) is increasingly used in chronic
      peritoneal dialysis, there is little knowledge about the clinical impact of PET
      in the acute setting. We report about more than threefold increases in lactate
      removal by adjusting the dialysis prescription according to the results of PET in
      an infant with severe congenital lactic acidosis.

PMID- 9259917
TI  - Theophylline concentration following equal doses of intravenous aminophylline and
      oral theophylline in preterm infants.
AB  - Steady-state serum theophylline concentrations following equal doses of
      intravenous aminophylline and oral theophylline were compared in 30 preterm
      infants with gestational age of 29.2 +/- 2.9 weeks. The result showed no
      significant statistical difference between the mean serum concentration of
      theophylline (8.2 +/- 2.2 micrograms/mL vs. 8.4 +/- 1.9 micrograms/mL; p =
      0.483). This indicates that a dose reduction of 20%, which is currently
      recommended, is not required when changing from intravenous aminophylline to oral
      theophylline. We conclude that in preterm infants, equal doses of intravenous
      aminophylline and oral theophylline maintain the same serum theophylline
      concentration.

PMID- 9259918
TI  - Amniotic fluid U. urealyticum colonization: significance for maternal peripartal
      infections at term.
AB  - The aim of this study was to examine the relationship between maternal peripartal
      infectious morbidity and amniotic fluid colonization by U. urealyticum. Amniotic
      fluid specimens for bacterial and mycoplasmal cultures were obtained by
      aspiration at nonelective cesarean section from 98 pregnant women. Amniotic fluid
      cultures revealed micro-organisms in 70 (71%) parturients and U. urealyticum was
      the most frequently isolated species, detected in the specimens from 38 (39%)
      women. In the total study population, the prevalence of clinically defined
      infectious morbidity was 26%, including 8 (8%) patients with chorioamnionitis, 11
      (11%) with endometritis, 5 (5%) with urinary tract infection, and 4 (4%) with
      wound infection. A significant association between the amniotic fluid U.
      urealyticum colonization and increased maternal peripartal infectious morbidity
      was observed (p < 0.0027; relative risk 4.1; 95% confidence limits 1.6 to 10.7).
      Amniotic fluids positive for U. urealyticum were significantly more often
      positive for other potentially pathogenic bacteria (p < 0.0024) and particularly
      for Bacteroides spp. (p < 0.0074). Our results support the existence of an
      association between amniotic fluid U. urealyticum invasion and maternal
      infectious morbidity. However, U. urealyticum was not usually isolated alone from
      amniotic fluids but combined with other pathogenic bacteria, the severity of
      infections were not enhanced when U. urealyticum was present and parturients with
      diagnosed infections managed well without specific antibiotic against U.
      urealyticum. Hence, it appears that the significance of U. urealyticum in
      maternal infections in this study population was mainly based on its interactions
      with other bacteria.

PMID- 9259919
TI  - Prostaglandin E2 for cervical ripening: a multicenter study of patients with
      prior cesarean delivery.
AB  - To evaluate the maternal and fetal outcomes of a large cohort of women treated
      with prostaglandin E2 (PGE2) gel for cervical ripening prior to trial of labor
      after previous cesarean delivery. Beginning in 1990 all pregnant patients with
      previous cesarean delivery presenting for prenatal care at 10 California
      hospitals were prospectively studied. We analyzed multiple parameters to compare
      outcomes of cases in which PGE2 gel was used to outcomes in a control group in
      which PGE2 was not used. Data were examined by X2 testing. During the study
      period 5022 patients underwent trial of labor after prior cesarean delivery. Of
      these 5022 patients, 453 (9%) were treated with PGE2 gel. There was no
      significant difference in the incidence of uterine rupture between the PGE2 group
      and the control group. Indicators of maternal and perinatal morbidity were not
      significantly higher in the prostaglandin treated group. The use of PGE2 gel for
      cervical ripening appears to be relatively safe in patients with prior cesarean
      delivery.

PMID- 9259920
TI  - Perinatal management of enteric duplication cysts of the tongue.
AB  - Intra-oral enteric duplication cysts are rare. We recently treated two infants
      with prenatally diagnosed large sublingual enteric duplication cysts. Antenatal
      aspiration of the cyst was attempted in one infant without success. Because of
      the potential for airway obstruction and respiratory distress at delivery,
      preparation for an immediate tracheostomy was made in case oral intubation was
      impossible. Fortunately, aspiration of the cyst provided adequate access to the
      oropharynx for intubation in both infants. The placental cord was not divided
      until the airway was secured to minimize the potential for anoxic injury.
      Complete excision of the cyst was subsequently done in one patient. The other
      infant had an initial marsupialization and laser ablation of the cyst mucosa but
      the cyst recurred. Cyst excision at 9 months of age resolved the problem.
      Pathological examination revealed columnar-lined mucosa consistent with enteric
      duplication cysts. An enteric duplication cyst may present as a large sublingual
      mass with potential for airway obstruction in the newborn infant. Antenatal
      diagnosis allows for the proper preparation of personnel and equipment in the
      management of these neonates during delivery. If the airway is compromised,
      aspiration of the cyst can be done to improve the access to the oropharynx for
      intubation. Preparation for emergent tracheostomy should be done before delivery
      in case oral intubation is not possible. Subsequent complete cyst excision is the
      treatment of choice.

PMID- 9259921
TI  - Developmental sequence of human fetal body movements in the second half of
      pregnancy.
AB  - To describe fetal body movements precisely and to clarify their developmental
      sequence in the second half of pregnancy, fetal body movements were observed in
      31 normal fetuses between 20 and 41 weeks of pregnancy by using multiple
      ultrasonic machines. All movements of the whole trunk were able to be classified
      into six fundamental movements: flexion, stretch, rolling, startle, stepping, and
      writhing. Startle was always observed as a single movement, but others were more
      frequently observed as a part of combination rather than as a single movements.
      The incidence of flexion and stretch peaked at 28-31 weeks, whereas the incidence
      of startle and stepping lowered at the period. The incidence of rolling and upper
      half trunk movements increased at 40-41 weeks. Limb movements were frequent and
      did not exhibit characteristic change in the incidence. In conclusion, we
      classified fetal body movements into several fundamental movements instead of
      using the expression of "general movements" by focusing principally on movements
      of the trunk. In particular, some of the fundamental movements seem to appear in
      characteristic ways as related to gestational age. In view of that fetal
      behaviors are closely related to the neural activity, the present findings may
      contribute to an understanding of the developmental process of the central
      nervous system.

PMID- 9259922
TI  - Antenatal steroids and intraventricular hemorrhage after premature rupture of
      membranes at 24-28 weeks' gestation.
AB  - To determine whether antenatal corticosteroid administration after midtrimester
      premature rupture of membranes (PROM) reduces the incidence or severity of
      neonatal intraventricular hemorrhage, we identified a cohort of infants delivered
      between 24 to 28 weeks gestation (n = 75) by mothers with PROM. Information was
      obtained from a computerized database (n = 3716) of all newborns admitted to the
      neonatal intensive care unit at a single medical center from 1991 to 1996. We
      reviewed records of each mother-infant pair to determine antenatal corticosteroid
      administration, presence, and severity of neonatal intraventricular hemorrhage,
      and frequency of infectious complications. Using a logistic regression model,
      antenatal corticosteroid administration was associated with a significantly
      reduced risk of severe (grade 3-4) intraventricular hemorrhage (0.1 odds ratio,
      0.006-0.57, 95% confidence interval), but not a reduced incidence of
      intraventricular hemorrhage (grade 1-4, 0.4 odds ratio, 0.12-1.05, 95% confidence
      interval).

PMID- 9259923
TI  - The effect of a resident night team on cesarean delivery.
AB  - We tested the hypothesis that the implementation of a resident night team would
      change the rate of, the indications for, and the time of day of cesarean
      delivery. A retrospective chart review was performed on patients who underwent
      cesarean birth during two time periods. Charts of 1722 patients who had a
      cesarean delivery between January 1, 1990 through June 30, 1991 (control group)
      and January 1, 1992 through June 30, 1993 (study group after implementation of a
      resident night team) were abstracted. All patients were cared for only by
      resident physicians and all patients delivered during a workweek defined as
      Sunday 1700 through Friday 0700. Each workday was divided into three shifts (0001
      0700; 0701-1700; and 1701-2400) for analysis. After implementation of the night
      team, the cesarean rate increased (p < 0.002), the proportion of planned repeat
      cesarean deliveries decreased, the proportion of cesareans for malpresentation
      decreased (p < 0.005), and the proportion of cesareans for arrest of labor
      increased (p < 0.0001). These changes were not associated with a change in the
      temporal distribution for any indication among the three shifts. The
      implementation of a resident night team did not change the time of day
      distribution of cesarean delivery for any of six indications.

PMID- 9259925
TI  - Transient alteration in fetal biophysical profile immediately following
      fetomaternal hemorrhage sustained during motor vehicle accident.
AB  - Transient altered fetal behavior manifested by decreased fetal biophysical score
      at 37 weeks' gestation following maternal injuries sustained in a motor vehicle
      accident, represented an immediate fetal response to fetomaternal hemorrhage
      occurring during the accident. Although cesarean delivery had initially been
      considered due to fetal distress (fetal biophysical score of 4 of 10), the fetal
      biophysical score improved within 2 hr, permitting spontaneous vaginal delivery
      of a nonasphyxiated fetus, 24 hr after the traumatic event. To our knowledge this
      is the first report of a transient abnormal fetal biophysical profile in
      association with a large fetomaternal hemorrhage.

PMID- 9259924
TI  - The Rubenesque pregnancy: a progression towards higher blood pressure correlates
      with a measure of endogenous and exogenous insulin levels.
AB  - Women with gestational diabetes tend to progress to noninsulin-dependent diabetes
      (NIDDM) with a high cumulative incidence relative to the general population.
      These women have also been shown to be insulin resistant and may represent a
      variant of the insulin resistance syndrome or Syndrome X. Our previous studies
      indicated that administered insulin was associated with an increase in blood
      pressure in women with gestational diabetes, raising the question that insulin
      levels per se contribute to blood pressure in these women. We developed a means
      by which the insulin levels of a given pregnant individual might be estimated
      called the Fraction of Circulating Insulin Level Relative to Normal (FOCILRN = C
      PEPTIDE/2.0 + TOTAL DAILY INSULIN DOSE/CALCULATED DAILY INSULIN REQUIREMENT BASED
      ON WEIGHT AND GESTATIONAL WEEK). The formula was applied to 15 nonhypertensive
      pregnant women of comparable obese phenotype (Rubenesque) with varying degrees of
      glucose tolerance (4 normal, 5 gestational diabetes treated with diet alone, 4
      gestational diabetes treated with insulin, and 2 noninsulin-dependent diabetes).
      Blood pressure was quantified at the beginning of the study (gestational weeks 24
      34) and again 4-8 weeks later using a 24-hr monitor. Correlation analysis was
      used to test for a relationship between the FOCILRN and blood pressure. The
      increase in mean arterial pressure was found to be continuous and linear with
      increasing insulin exposure as quantified by FOCILRN. The correlation was
      significant for all subjects (r = 0.961, p < 0.001) and remained significant even
      with removal of patients with NIDDM (r = 0.857, p < 0.001). The nighttime heart
      rate, systolic and diastolic blood pressures were found to be significantly
      correlated with FOCILRN (r = 0.651, p < 0.01, r = 0.724, p < 0.001, and r =
      0.831, p < 0.001, respectively). The difference between the maximum and minimum
      diastolic blood pressure values between 12:00 AM and 6:00 AM between sessions 1
      and 2 significantly differed among the groups with women on insulin having the
      highest FOCILRN having the least variation in blood pressure. In nonhypertensive
      women of obese phenotype (Rubenesque), increasing insulin exposure is associated
      with increasing mean arterial blood pressure and less variability of nocturnal
      blood pressure. These data provide support for the hypothesis that insulin may
      mediate blood pressure response in genetically vulnerable individuals. The
      identification of the Rubenesque phenotype during gestation may be a clinically
      useful marker for individuals at risk for Syndrome X.

PMID- 9259926
TI  - Sonographic imaging of the fetal face and the establishment of normative
      dimensions for chin length and upper lip width.
AB  - Sonographic imaging of the fetal face is important because a number of
      chromosomal aberrations are associated with facial malformations. Prenatal
      diagnosis of abnormalities of the fetal chin and lips have been based on
      subjective assessment. The purpose of the current study was to establish
      normative dimensions for the objective assessment of the fetal face. A cross
      sectional study was performed in 200 normal healthy singleton pregnancies between
      16 and 38 weeks' gestation. Inclusion criteria included performance of a first or
      early second-trimester scan to confirm gestational age (GA). Exclusion criteria
      included birth weight < 10th or > 90th percentile for GA, and medical
      complications of pregnancy. Ultrasound measurements were made in the mid-sagittal
      plane and included chin length (CL) and upper lip width (ULW). A first-degree
      linear growth function was observed throughout pregnancy between GA and ULW (r =
      0.87) and CL (r = 0.91). All measured data are expressed as mean +/- 2 SD. In
      conclusion, these results provide normative dimensions throughout gestation for
      the fetal upper lip and chin. These data are expected to serve as a basis for the
      objective assessment of the fetal face in high-risk conditions.

PMID- 9259927
TI  - Prolonged apnea in the preterm infant is not a random event.
AB  - We tested the hypothesis that in preterm infants, prolonged apneas (apneas > or =
      20 sec) are not random events but are preceded by frequent and progressively
      longer respiratory pauses associated with changes in ventilatory variables. We
      studied 36 preterm infants with apnea [birth weight 1190 +/- 60 g (mean +/- SEM),
      study weight 1300 +/- 60 g, gestational age 28 +/- 1 weeks, and postnatal age 23
      +/- 2 days]. A nosepiece with a flow-through system was used to measure
      ventilation and alveolar gases. Throughout the monitoring period for each infant
      we established 10-min moving "window of observation" followed by a 1-min interval
      examined for the detection of a prolonged apnea. Within the 10-min window, three
      variables were defined: the number of apneic episodes, the maximum length of a
      single apneic episode, and the total duration of apneic time. During the
      following minute (eleventh) the presence or absence of a prolonged apnea was
      determined. Chi-square test for a linear-trend in the rate of prolonged apnea and
      multiple logistic regression analysis showed that the relative risk of a
      prolonged apnea increases significantly from preceding periods without apnea to
      preceding periods containing the potential predictors of prolonged apnea. The
      strongest predictor was total duration of apneic time in the previous 10 min.
      When the 1 min before prolonged apnea was compared with the 1 min of similar
      sleep state not having prolonged apnea, minute ventilation decreased, primarily
      due to a decrease in respiratory frequency. Oxygen saturation decreased and
      alveolar PCO2 did not change. These findings suggest that prolonged apnea is not
      a random event but is preceded by a disturbance of the respiratory control system
      characterized by (1) frequent apneas of progressive duration, (2) decrease in
      respiratory minute volume and frequency, and (3) decreased O2 saturation.

PMID- 9259928
TI  - Corticosteroid binding globulin, total serum cortisol, and stress in extremely
      low-birth-weight infants.
AB  - Our objective was to determine if low levels of corticosteroid binding globulin
      (CBG) might explain the low serum total cortisol levels found in some extremely
      low-birth-weight (ELBW) infants. In a prospective study, serum total cortisol and
      CBG were measured in single blood samples from 31 ELBW infants, with a
      gestational age less than 28 weeks, in the first 8 days of life. Severity of
      illness was assessed using the Score for Neonatal Acute Physiology Perinatal
      Extension (SNAP-PE). The mean serum total cortisol (mean +/- 1 SD) was 9.2 +/-
      9.8 mcg/mL and the mean CBG level was 1.4 +/- 0.31 mg/dL. There was no
      significant correlation between serum total cortisol and CBG levels (r = -0.18),
      severity of illness as measured by the SNAP-PE (r = +0.12), or birth weight (r = 
      0.12). Five of 31 infants, having a mean SNAP-PE score of 41, had serum total
      cortisol levels < or = 3.0 mcg/dL. Estimated mean serum free cortisol
      concentrations in these five infants (0.76 mcg/dL) were comparable to estimated
      free cortisol levels diagnostic of adrenal insufficiency in sick adult patients.
      Our findings indicate that CBG levels are lower in ELBW infants than in term
      infants, but low CBG levels do not explain the low serum total cortisol levels
      found in some very sick infants. Low cortisol levels in small premature infants
      may be adequate to support growth if the infant is well, but may result in a
      syndrome of adrenal insufficiency in those with severe illnesses.

PMID- 9259929
TI  - Isolated ductal closure in utero diagnosed by fetal echocardiography.
AB  - In utero isolated ductal closure is uncommon and can lead to fetal hydrops and
      death if not recognized. Five fetuses were diagnosed prenatally by
      echocardiography. The reasons for referral were hydrops (2), cardiomegaly (1),
      polyhydramnios and choroid plexus cyst (1), and polyhydramnios and teratoma of
      the neck (1). Gestational age was median 32, range 18-41 weeks. Two mothers
      received indomethacin for polyhydramnios, with the echocardiogram performed 5 and
      3 days after the last dose. Three had a negative history of drug ingestion. Fetal
      echocardiograms showed absent flow in the ductus arteriosus, dilated right
      ventricle with decreased function, and mild or moderate tricuspid and pulmonary
      insufficiency in all. The left ventricle was hypercontractile, with significantly
      increased left ventricular stroke output when compared to the right. Four fetuses
      were delivered by cesarean section and had an uneventful course. One fetus died
      shortly after birth due to airway obstruction from a large teratoma. Autopsy
      showed ductal constriction. Postnatal echocardiograms showed absent ductal flow
      and dilated right ventricle. On follow-up, survivors remained asymptomatic with
      cardiac size returning to normal. Premature closure of the ductus arteriosus
      should be considered in hydrops of unknown etiology, right ventricular
      dysfunction, and following indomethacin therapy. Urgent delivery results in an
      excellent prognosis.

PMID- 9259930
TI  - Cerebral palsy in infants with asymmetric growth restriction.
AB  - The relationship between low ponderal index and cerebral palsy was evaluated.
      National Collaborative Perinatal Project and University of California Child
      Health and Development Study data were analyzed. Associations between low
      ponderal index (ponderal index < 5% for gestational age) were evaluated in the
      combined population, in term and preterm infants, and in non-SGA infants (with
      birth weights > 5% for gestational age and gender). Data from 55,571 infants,
      including 232 cases of cerebral palsy, were evaluated. Low ponderal index was
      significantly associated with CP in the delivery population (Relative risk 2.2)
      and in non-SGA infants (RR 1.9). Low ponderal index was a significant independent
      correlate of cerebral palsy (RR 1.9) in non-SGA infants after using logistic
      regression to correct for effects of prematurity and gender. Low ponderal index
      is associated with increased risk of CP, even in non-SGA infants. Assessment of
      the neonatal ponderal index provides an additional method of documenting prior
      abnormal fetal growth and development.

PMID- 9259931
TI  - Prolonged fetal bradycardia secondary to maternal hypothermia in response to
      urosepsis.
AB  - Fetal bradycardia is a well-known response to maternal hypothermia, as induced at
      open-heart surgery, but heretofore has not been reported in conjunction with
      hypothermia from urosepsis. A 24-year-old Vietnamese woman admitted at 33 weeks
      estimated gestational age with pyelonephritis secondary to Escherichia coli
      developed several episodes of maternal hypothermia to 35-36 degrees C. During
      each episode of maternal hypothermia, the baseline fetal heart rate fell to 90
      100 bpm, but with retained reactivity. During each episode, maternal vital signs
      were otherwise stable and oxygen saturation was normal as measured by pulse
      oximetry. Interpretation of fetal bradycardia during episodes of maternal
      urosepsis is complex. If seen in conjunction with maternal hypothermia, and in
      the presence of normal maternal cardiac and respiratory function, bradycardia is
      unlikely to represent fetal distress.

PMID- 9259932
TI  - The Santa Barbara County Health Care Services program: birth weight change
      concomitant with screening for and treatment of glucose-intolerance of pregnancy:
      a potential cost-effective intervention?
AB  - Macrosomic infants still suffer birth trauma in excess of the general population;
      thus, while debated, the medical and legal sequelae of macrosomia appear to be
      costly. The clinical role of maternal hyperglycemia below the threshold for the
      diagnosis of gestational diabetes (GDM) in the etiology of macrosomia remains an
      area of controversy. Based on the hypothesis that increasing glucose levels
      result in an increasing prevalence of macrosomia, we designed a study to observe
      the impact on birth weight and on cost of a treatment program for glucose
      intolerant pregnant women in The Santa Barbara County Health Care Services
      (SBCHCS). In 1985, 18% of 4364 births (85% Mexican-American in origin) in the
      SBCHCS were > 90th percentile birth weight. In 1986, we began a program to treat
      all glucose-intolerant pregnant women who had a positive glucose challenge test
      (GCT > 140 mg/dL after a 50-g oral glucose load), even if they had a negative
      glucose tolerance test. All glucose-tolerant pregnant women were placed on a 40%
      carbohydrate, 1800 kcal diet and taught to monitor their blood glucose. Insulin
      was begun if the fasting blood glucose was > 90 mg/dL and/or the 1-hour post meal
      was > 120 mg/dL. After introduction of the screening/ treatment program, the
      prevalence of macrosomia in 1992 was 7% and the cesarean section rate had dropped
      from 30 to 20%. The cost to SBCHC to educate and treat the additional glucose
      intolerant women was $233,650. Assuming that there would have been an additional
      398 macrosomic infants with some requiring cesarean delivery and intensive care,
      total potential savings could be estimated at $833,870 per year. Thus, treatment
      of glucose-intolerant pregnant women was associated with a decrease in macrosomia
      and may be cost-effective.

PMID- 9259933
TI  - The effect of vibroacoustic stimulation on fetal heart rate parameters utilizing
      computer analysis.
AB  - We examined the effect of vibroacoustic stimulation on periodic and nonperiodic
      fetal heart rate (FHR) parameters in fetuses not meeting Dawes-Redman criteria
      utilizing computerized analysis. Antepartum FHR analysis was performed using the
      Oxford Sonicaid System 8000 package (Oxford Sonicaid Ltd., Chichester, UK).
      Patients not meeting Dawes-Redman criteria for reactivity after 20 min of
      monitoring were recruited for the study. A 3-sec vibroacoustic stimulation (VAS)
      to the maternal abdomen was then performed over the fetal head. Each patient was
      again monitored using the System 8000. FHR parameters were compared before and
      after fetal VAS using the paired Student's t-test. Twenty patients met the study
      criteria. The average gestational age at testing was 36 weeks. Following fetal
      VAS, significant increases were observed in the number of fetal movements, number
      of accelerations, baseline FHR, overall variation, and short-term variation. No
      significant changes occurred in the number of decelerations. Dawes-Redman
      criteria were met in 16 patients after fetal VAS. In fetuses not initially
      meeting Dawes-Redman criteria, VAS is associated with increased long-term
      periodic changes in FHR, but not with changes in the number of fetal heart rate
      decelerations. Furthermore, by computerized analysis, VAS is also associated with
      increased overall and short-term FHR variability.

PMID- 9259934
TI  - The efficacy of prophylactic erythromycin in preventing vertical transmission of
      Ureaplasma urealyticum.
AB  - To determine if prophylactic erythromycin alters the vertical transmission rate
      of Ureaplasma urealyticum. Randomized prospective study of 51 singleton
      pregnancies between 22 and 35 weeks' gestation with preterm premature rupture of
      membranes or preterm labor. Patients received oral erythromycin for 7 days in
      addition to routine prophylactic intravenous ampicillin or ampicillin alone.
      Lower genital colonization with U. urealyticum was 33 of 51 (65%). Vertical
      transmission of U. urealyticum was 25% (3 of 12) in the erythromycin group and 4
      of 17 (24%) for the controls. The average interval from randomization to delivery
      was 303.5 hr in the erythromycin group and 70.9 hr for controls (p = 0.04).
      Although not statistically significant, histologic chorioamnionitis in patients
      colonized with Ureaplasma was lower in the erythromycin group (3 of 12, 25%)
      compared to the controls (10 of 17, 59%). Prophylactic erythromycin does not
      decrease vertical transmission of Ureaplasma. It may decrease the incidence of
      histologic chorioamnionitis and increase the latency period.

PMID- 9259935
TI  - Interpretation of the TDx-FLM fluorescence polarization assay in pregnancies
      complicated by diabetes mellitus.
AB  - The objective of this paper is to determine the applicability of the Abbott TDx
      FLM fluorescence polarization assay in pregnancies complicated by diabetes
      mellitus. Retrospective review of records of women with pregnancies complicated
      by diabetes who underwent amniocentesis for fetal lung maturity using the Abbott
      TDx-FLM assay within 3 days of delivery was considered. Maternal diabetic
      control, neonatal birth weight, Apgar scores, umbilical cord gases, admissions to
      Neonatal Intensive Care Unit (NICU), development of respiratory distress syndrome
      (RDS) were evaluated. One hundred twenty-one patients with diabetes mellitus were
      identified. Thirteen (10.7%) had an FLM < or = 70 mg/g and 108 patients had > or
      = 70 mg/g. All obstetrical and diabetic variables were similar. RDS was not
      observed in neonates who had an FLM of > or = 70 mg/g. One neonate had RDS (FLM =
      7.2 mg/g). The TDx-FLM > or = 70 mg/g may be interpreted as mature when obtained
      from transabdominal amniocentesis.

PMID- 9259936
TI  - Cesarean deliveries at a university hospital: analysis of rates and indications.
AB  - The objective of this paper is to evaluate the influence of patient risk status
      on the incidence of and indications for cesarean delivery. All live births > or =
      23 weeks at the University of Vermont in 1995 (n = 2395) were retrospectively
      analyzed for delivery route, indication for cesarean, gestational age, parity,
      and practice group (to reflect risk status). The total cesarean rate was 14.4%
      (344 of 2395), and the primary rate was 11.4% (244 of 2144). Abnormal
      presentation was the most common indication (25.6%, 88 of 344). The "corrected"
      cesarean rate (maternal-fetal medicine and transported patients excluded) was
      12.4% (273 of 2194), and the "corrected" primary rate was 9.6% (190 of 1975).
      Furthermore, when all deliveries were analyzed, regardless of risk status but
      limited to gestational age > or = 36 weeks, the rates did not change (12.6%, 280
      of 2214; primary 9.2%, 183 of 1994). Arrest of dilation was the most common
      indication in both "corrected" subgroups (23.4 and 24.6%, respectively). Cesarean
      rates at tertiary care hospitals should be compared with rates at community
      hospitals only after correcting for dissimilar patient groups or gestational age.

PMID- 9259937
TI  - Increase in ambient temperature may explain decrease in amniotic fluid index.
AB  - In the third trimester, the amniotic fluid index (AFI) may be affected by
      maternal fluid status. As the ambient temperature increases, there is an increase
      in insensible fluid loss and the potential for dehydration. We hypothesize that
      as temperature increases there would be a concomitant decrease in AFI. From June
      11 to August 16, 1993, during a period of unusual high heat, 42 women with
      singleton pregnancies between 27 and 40 weeks' gestation undergoing serial
      antenatal testing had AFI determinations recorded at least weekly. The daily high
      ambient temperature in our urban area was subsequently obtained. A 2-, 3-, and 4
      day mean temperature prior to the test date was compared to AFI using a Spearman
      rank Correlation. The daily high temperature ranged from 71 to 104 degrees F and
      AFI values ranged from 1.7 to 24.7 cm during the study period. There was a
      significant correlation between the 2-, 3-, and 4-day mean temperature and AFI,
      with the 4-day mean being the most significant (r = 0.31, p < 0.001).
      Fluctuations in ambient temperature are inversely correlated to changes in AFI.
      This relationship should be taken into account when interpreting the AFI as a
      measure of fetal well-being.

PMID- 9259938
TI  - Early treatment of gestational diabetes reduces the rate of fetal macrosomia.
AB  - This study tested the hypothesis that to reduce the rate of macrosomic infants in
      gestational diabetes cases, good glycemic control should be initiated before 34
      completed gestational weeks. The study population included 84 women with
      gestational diabetes, ascertained by universal screening of all women attending
      the antenatal clinic of the Hadassah Medical Center, over a 2-year period. The 60
      women (71%), who initiated treatment before 34 completed weeks, composed the
      "early" group. The 24 women (29%), who initiated treatment after the 34th week,
      composed the "late" group. All patients were managed by an intensified protocol,
      including stringent glycemic control. In the "early" and "late" groups, mean
      gestational age at the beginning of treatment was 30.0 +/- 3.8 and 36.2 +/- 1.2
      weeks, and duration of treatment was 9.6 +/- 4.1 and 3.7 +/- 1.8 weeks,
      respectively. Maternal characteristics were similar in the two groups. The rate
      of macrosomic and large-for-gestational-age infants were 5 and 11%, respectively,
      in the early group as compared to 25 and 29% in the "late" group (p < 0.05). No
      significant differences were found between the two groups in the mode of delivery
      or Apgar scores. We conclude that to reduce the rate of macrosomic infants in
      gestational diabetes cases, good glycemic control should be initiated before 34
      completed gestational weeks.

PMID- 9259939
TI  - Antenatally detectable markers for the diagnosis of autosomally trisomic fetuses
      in at-risk pregnancies.
AB  - Our aim was to investigate the contribution of certain antenatally detectable
      markers leading to the diagnosis of trisomic fetuses we observed over a period of
      6 years. In our study, we specifically analyzed the role played by advanced
      maternal age and sonographically discovered abnormalities in the detection of
      autosomal trisomies. All together, 27 fetuses had this disorder, representing
      28.7% (27 of 94) of all cytogenetic aberrations detected at our center over the
      same period. Down syndrome (12 cases) and Edward syndrome (11 cases) were the
      most common trisomies, while 4 cases of Patau syndrome were also diagnosed. The
      most common indication leading to diagnosis was abnormal ultrasound finding
      (48.2%), followed by advanced maternal age (44.4%). However, 63% of the trisomic
      fetuses belonged to mothers aged 35 years and above. Down syndrome fetuses
      (41.7%) had prenatally detected sonographic anomalies, 63.6% for Edward syndrome,
      and all fetuses with Patau syndrome (4 of 4) showed abnormal sonographic signs.
      Trisomy 21 presented with the following features: hydramnios, complex
      malformations, pyelectasis, and duodenal atresia. Trisomy 18 fetuses showed
      hydramnios, intrauterine growth retardation, microcephaly, spina bifida, and
      nonimmune hydrops fetalis. Signs observed in fetuses with trisomy 13 were:
      hydrocephalus, intrauterine growth retardation, oligoanhydramnios, complex
      malformations, severe fetal bradycardia and hydronephrosis.

PMID- 9259940
TI  - The rate of severe preeclampsia is increased in triplet as compared to twin
      gestations.
AB  - The objective of this study was to determine if the rate of preeclampsia is
      increased in triplet as compared to twin gestations. Fifty-three triplet
      pregnancies between 1986 and 1993 at The New York Hospital-Cornell Medical Center
      were reviewed. These were matched for maternal age, parity, and race to twin
      gestations (N = 53) from the same population. Severe preeclampsia was defined by
      standard criteria. Student's t-test, Fisher exact test, and Chi-square were used
      for statistical analysis. The rate of severe preeclampsia was increased
      significantly in the triplet group 12 of 53 (22.6%) as compared with the twin
      group 3 of 53 (5.7%) (OR = 4.9, 95% CI 1.2-23.5, p = 0.02). The rate of overall
      preeclampsia was not significantly different in the triplet 18 of 53 (33.96%) or
      twin 12 of 53 (22.6%) groups. In this retrospective, case-controlled study, the
      rate of severe pre-eclampsia was significantly increased in triplet gestations as
      compared to twins although the overall rate of preeclampsia was not. This
      information may be useful in counseling patients with high order multifetal
      gestations.

PMID- 9259941
TI  - Thermal equipment usage patterns in neonatal intensive care units: interunit
      variability and intraunit consistency.
AB  - We conducted a survey and audit of thermal equipment use in very low-birth-weight
      infants in five Ohio neonatal intensive care units (NICUs) to document regional
      practice. The survey indicated a variety of thermal care styles. Two NICUs
      preferred to admit infants to incubators, the other three favoring radiant
      warmers. These three NICUs moved infants from radiant warmers into incubators at
      significantly different mean ages. The audit demonstrated inconsistent use of
      plastic covers, warming mattresses, and added humidity under radiant warmers, and
      discrepancies between survey responses and actual use within NICUs. Inter-NICU
      variability of thermal equipment use may complicate fluid management.

PMID- 9259942
TI  - Massive fetomaternal hemorrhage.
AB  - This report describes a full-term newborn with massive fetomaternal hemorrhage.
      Fetal movements were decreased 48 hr prior to delivery. On the day of delivery,
      they were absent. The nonstress test was abnormal with low biophysical profile
      and decreased beat-to-beat variability. The infant presented with extreme pallor,
      hypotonia, hepatosplenomegaly, and ascites. The initial hemoglobin was 2.2 g/dL,
      the Kleihauer-Betke stain was 27.6% (highest level ever reported). Right temporal
      and cerebellar hemorrhages were present. Sequelae include severe developmental
      delay and asymmetric double hemiplegia.

PMID- 9259943
TI  - Perinatal features of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS
      complex) associated with large meningomyeloceles and severe limb defects.
AB  - Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS complex), a
      combination of omphalocele, exstrophy of the bladder, an imperforate anus and
      spinal defects, arises from a single localized defect in the early development of
      the mesoderm that will later contribute to infraumbilical mesenchyme, cloacal
      septum, and caudal vertebrae. In this report, we document the perinatal features
      of two cases of OEIS complex associated with meningomyeloceles and severe lower
      limb defects, and discuss the prenatal diagnosis, inheritance, and differential
      diagnosis of this association of malformations. Although long-term survival can
      be achieved by successful corrective surgery, the associated structural defects
      such as large meningomyelocele and severe limb aplasia or hypoplasia, as seen in
      our patient, can influence the patient's quality of life. We would like to
      emphasize that an accurate prenatal diagnosis of OEIS complex and associated
      malformations is important for the detailed counseling of the family as well as
      appropriate perinatal management by the obstetricians, pediatric surgeons,
      urologists, neurosurgeons, and neonatologists.

PMID- 9259944
TI  - Subchorial hematoma: a probable cause of reversible nonimmune hydrops fetalis.
AB  - Nonimmune hydrops fetails diagnosed at 21 weeks' gestation with profound ascites,
      hydrothorax, and pericardial effusion receded gradually with regression of a
      subchorial placental lucencies immediately below the umbilical cord insertion.
      Careful inspection of the delivered placenta revealed that there was a yellowish
      lesion of fibrin deposits below the cord insertion site, which resulted from the
      absorption of hematoma. A subchorial placental hematoma, which detected as a
      subchorial placental lucencies by ultrasonography, can be a cause of reversible
      nonimmune hydrops fetalis.

PMID- 9259945
TI  - Preterm premature rupture of the membranes associated with recent cocaine use.
AB  - The objective of this study was to determine the rate of recent cocaine use among
      a metropolitan population of predominantly Hispanic and African-American women
      with preterm premature rupture of the membranes (PROM) and to ascertain the
      impact of cocaine on the latency period between rupture of membranes and
      delivery. Urine toxicology screens were prospectively obtained on 147 women with
      preterm PROM. The urine screen did not influence management decisions. All women
      were expectantly managed without tocolytics until 37 weeks' gestation unless they
      developed clinical chorioamnionitis, or nonreassuring fetal heart rate tracing or
      biophysical profile. Demographic information, hours from rupture of membranes to
      delivery, gestational age, and birth weight at delivery were compared using
      Fisher's exact, Mann-Whitney U, and randomization tests where appropriate. The
      rate of positive urine drug screens for cocaine was 8.2%. Women in the cocaine
      positive group were of higher parity (3, [0-7]vs. 1, [0-6], p = 0.001) and tended
      to be older (27, [23-42]vs. 25, [14-40]). There was a higher rate of recent
      cocaine use among African-American women (20.4%) as compared to non-African
      Americans (1.2%, p = 0.0001). Cocaine-positive women presented at an earlier
      gestational age (32 weeks', [24-34]vs. 33 weeks', [23-36], p = 0.02) and had a
      significantly longer membrane rupture to delivery interval than women with a
      negative urine drug screen (174 hr, [6-475]vs. 33 hours [1-833], p = 0.01). There
      was no significant difference in the reason for delivery between the two groups
      of patients. Recent cocaine use among women with preterm PROM is common in only
      some segments of an urban population. Women with recent cocaine use present with
      ruptured membranes at an earlier gestational age and may actually have a longer
      latency period than women who do not use cocaine.

PMID- 9259946
TI  - Emphysematous chorioamnionitis diagnosed by ultrasonography.
AB  - Preterm labor, cervical cerclage (especially when performed as an emergency
      procedure), and diabetes mellitus are all associated with an increased risk of
      chorioamnionitis. It might be expected that the combination of all 3 could lead
      to especially severe infection. We report such a case. A woman with a history of
      two spontaneous midtrimester abortions had had cervical cerclage performed at 13
      weeks. She was referred at 24 weeks' gestation with preterm labor, and the cervix
      was found to be dilated. An emergency repeat cerclage was performed. The
      following day, ultrasonography revealed the presence of intra-amniotic gas.
      Infection was confirmed by the presence of a purulent cervical discharge, a
      neutrophilia with a left shift, and an elevated C-reactive protein level. The
      cervical stitch was removed and labor induced. The infant was liveborn, but
      succumbed to the complications of prematurity and sepsis. E. coli was isolated.
      In her subsequent pregnancy, severe gestational diabetes was diagnosed and
      following pregnancy, permanent diabetes mellitus was confirmed. The combination
      of infection, diabetes, and intact membranes may lead to a particularly severe
      form of chorioamnionitis, with the production of gas within the amniotic cavity.
      Infection should be excluded before emergency cervical cerclage, especially in
      the woman with diabetes mellitus.

PMID- 9259947
TI  - Pregnancy in chronic progressive external ophthalmoplegia: a case report.
AB  - The mitochondrial diseases are uncommon multisystem disorders characterized by
      the presence of functionally and/or structurally abnormal mitochondria. As there
      have been few reports of the obstetrical care of affected patients, we wish to
      document two pregnancies in a woman with a Chronic Progressive External
      Ophthalmoplegia (Kearns-Sayre-like syndrome). Both pregnancies were complicated
      by preterm labor and hypertension.

PMID- 9259949
TI  - Effect of magnesium sulfate on the development of cystic periventricular
      leukomalacia in preterm infants.
AB  - To determine if magnesium sulfate has an effect on the development of cystic
      periventricular leukomalacia in preterm infants, this retrospective case control
      study was conducted. There were 23,382 infants born at three teaching hospitals
      in the metropolitan New York area from January 1992 to December 1994. Four
      hundred ninety-two infants met our entrance criteria. Criteria included a birth
      weight < 1750 g, survival to at least 7 days of life and at least one cranial
      ultrasound after 7 days of life. Infants exposed to magnesium sulfate in utero
      were less likely to develop periventricular leukomalacia. Two of 18 (11%) infants
      with periventricular leukomalacia were exposed to magnesium sulfate in-utero
      compared to 14 of 36 controls (39%) (p = 0.035) (OR = 0.196, 95% CI = 0.039
      0.988). Pre-eclampsia as an independent factor was not associated with a reduced
      risk (p = 0.251) (OR = 0.294, 95% CI = 0.033-2.65). Preterm infants exposed to
      antenatal magnesium sulfate were found to have a reduced risk of developing
      cystic periventricular leukomalacia.

PMID- 9259948
TI  - A discriminant function for preeclampsia: case-control study of minor
      hemoglobins, red cell enzymes, and clinical laboratory values.
AB  - A case-control study was performed in eight pairs of women to determine whether
      preeclamptic women developed abnormalities in minor hemoglobins, glycolytic
      enzymes, or other blood components that might provide insight into the
      pathophysiology of preeclampsia, or that in combination might be used as a marker
      for the condition. These variables and standard clinical tests were analyzed as
      discriminators between preeclamptic and control women. The subjects were matched
      for age, ethnicity, parity, and gestational age. Blood samples were taken at the
      time of diagnosis of preeclampsia and at comparable gestational ages for matched
      normal controls. Variables differing significantly between groups included
      increases in uric acid (UA), low-density lipoproteins (LDL), phosphoglycerate
      kinase (PGK), and mean platelet volume (MPV), and decreases in glyceraldehyde
      phosphate dehydrogenase (G3PD) in preeclamptic women compared to normal controls.
      Discriminant analysis revealed the following function to separate the groups:
      0.7764 (UA) + 0.8086 (PGK) -0.7032 (G3PD) + 0.1399 (LDL) -0.2386 (MPV). A
      discriminant score of > or = 275 indicated a > or = 90% probability of
      preeclampsia. The results are consistent with perturbations in red cell
      glycolysis in preeclampsia. Further prospective studies are warranted to test the
      efficacy of this discriminant function in predicting preeclampsia.

PMID- 9259950
TI  - A new protocol for the treatment of hand deformities in recessive dystrophic
      epidermolysis bullosa (13 cases).
AB  - The recessive form of dystrophic epidermolysis bullosa creates severe hand
      deformities with disabling functional limitations in the main daily activities.
      Typically, the thumb is contracted in adduction, the first web space is
      obliterated, the palm and digits are contracted in flexion and interdigital
      spaces are lost (pseudo-syndactyly). In this paper, we present our experience
      with a protocol based on the association of various internationally developed
      techniques: brachial plexus anesthesia with ketamine sedation, dynamic splinting
      and coverage of the wounds with allogenic keratinocytes sheets. The overall
      results obtained in the first 13 patients showed a good tolerance of the
      procedure, no anesthesiologic complication and marked improvement of the hand
      deformities. The long-term follow-up revealed a recurrence before 2 years in 2
      hands, between 2 and 4 years in 7 hands and after 4 years in 6 hands. The
      conclusion is that an aggressive surgical attitude, along with an adequate intra
      and post-operative rehabilitation, ensures a good restoration of hand function
      and a satisfying delay of inevitable recurrence.

PMID- 9259951
TI  - The radial Chinese flap at the expense of the palmar radiocarpal arch. A case
      report.
AB  - The retrograde flow Chinese flap has been shown to be a useful cover for
      extensive losses of palm tissue. We report a case in which vascularization was
      based on the palmar radiocarpal arch, with angiographic verification, in view of
      the post-injury absence of palmar arches. Considering the results obtained, the
      technical modifications introduced with respect to earlier studies are described
      (flap pivoting 2 cm from the Lister tubercle), and the palmar anastomotic network
      of the carpal bones is proposed as a new end effective vascular axis in the
      preparation of retrograde flow antebrachial axial flaps with an intact volar
      radiocarpal region.

PMID- 9259952
TI  - Prevalence of neural tube defects in northeastern France, 1979-1994. Impact of
      prenatal diagnosis.
AB  - The objective of this study was to determine in total prevalence of neural tube
      defects (NTD) in northeastern France during 1979-1994 inclusive, the impact of
      prenatal diagnosis on birth prevalence. All births and termination of pregnancy
      affected by NTD were ascertained from multiple sources thank to our registry of
      congenital anomalies. In our region maternal serum alpha-fetoprotein screening is
      not available whereas routine ultrasonographic screening of congenital anomalies
      is performed in all pregnant women. Total prevalence of NTD during 1979-1994 was
      10.73 per 10,000 with no upward or downward trend. The total prevalence of NTD in
      our region remained stable. However birth prevalence fell significantly. The fall
      was 100 per cent for anencephaly and 60 per cent for spina bifida. This birth
      prevalence was unchanged for encephalocele. This decrease for anencephaly and
      spina bifida was obtained by routine ultrasonographic examination only and
      termination of pregnancy. Comparison with similar studies in other countries
      demonstrated that screening by maternal serum alpha-fetoprotein is needed in our
      region.

PMID- 9259953
TI  - Intriguing association between disease associated unstable trinucleotide repeat
      and CpG island.
AB  - Expansion of (C+G)-rich trinucleotide repeats has been shown to be associated
      with several autosomal or X-linked genetic diseases and/or fragile sites. By
      analysing the sequences available in the databases, we found, in a significant
      proportion of triplet associated genes or fragile sites (11/12), a CpG island
      close to the trinucleotide repeat. This association led us to assume that
      flanking regions and chromatin structure near the triplets might play a role in
      repeat instability.

PMID- 9259954
TI  - Familial aggregation of malignant melanoma/dysplastic naevi and tumours of the
      nervous system: an original syndrome of tumour proneness.
AB  - A five-generation family is here reported in which several members developed
      malignant melanoma, dysplastic naevi, astrocytoma in all grades, benign or
      malignant schwannoma, neurofibroma, or meningioma in a single instance.
      Significant cosegregation of skin and nervous tumours, preclusion of allelism to
      type 1 neurofibromatosis and phenotypic departure from known syndromes of
      hereditary proneness to cancer make one suggest an original familial
      predisposition to both malignant melanoma and central/peripheral nervous tumours.

PMID- 9259955
TI  - Chromosome aberrations after radiotherapy in patients treated for non Hodgkin's
      lymphoma.
AB  - Chromosome aberrations were evaluated in the lymphocytes of 30 patients who had
      undergone radiotherapy several years before for non-Hodgkin's lymphoma. Twelve
      had received 20 Gy over the entire abdomen (group I), 12 wholebody irradiation at
      1.5 Gy (group II) and 6 wholebody irradiation at 15 Gy (group III). Unirradiated
      patients seen for cytogenetic analysis during the same period served as controls.
      Overall results for the irradiated population were 13/27 (48%) evaluable patients
      with chromosome aberrations and 50/710 (7%) abnormal cells for a total of 73
      aberrations (unstable: 35, stable: 38). The frequency of aberrations was
      statistically higher in group I (12% of cells) than in groups II (3.5%, p <
      0.0001) and III (2.5%, p < 0.0002). Differences in irradiation dose and volume
      may account for the variations between groups.

PMID- 9259956
TI  - Combined use of cytogenetic analysis and FISH for the identification of two
      antenatal de novo markers as Robertsonian translocations involving the p arms.
AB  - In two prenatal cases, de novo nonmosaic bisatellited marker chromosomes were
      studied with the combined use of fluorescence in situ hybridization (FISH) with
      chromosome specific probes and cytogenetic heteromorphisms. The FISH studies
      showed that one of the small accessory chromosome could be a heterozygous 14/15
      or 15/22 translocation involving the p arms of these chromosomes, the other
      showed only one hybridization spot with the classical satellite probe of
      chromosome 15. The analysis of heteromorphisms of the parental acrocentric
      chromosomes demonstrated that the two markers were Robertsonian translocations
      involving in the first case the p arms of the maternal 15 and 22 chromosomes and
      in the second case the p arms of the maternal 14 and 15 chromosomes.

PMID- 9259957
TI  - Mosaic trisomy 14 with hepatic involvement.
AB  - Mosaic trisomy 14 in liveborns is rare and may be accompanied by uniparental
      disomy in the euploid cell line. We report the case of a 6 month old male with
      growth failure, microcephaly, macroglossia, developmental delay, hypotonia,
      congenital heart disease, neonatal hepatitis, cryptorchidism, talipes
      equinovarus, limb length asymmetry, bilateral overriding of 1st by 2nd toe, and
      extended abnormal pigmentation in a linear-whorl distribution. The proband's
      karyotype in peripheral lymphocytes and skin fibroblasts was mos47,XY,+14/46,XY.
      Parental blood chromosomes were normal. Molecular analysis excluded uniparental
      disomy in the euploid cell line of the proband.

PMID- 9259958
TI  - Multiple (up to seven) different accessory small marker chromosomes: prenatal
      diagnosis and follow-up.
AB  - We report on the prenatal discovery of 3 up to 7 accessory small marker
      chromosomes per cell with postnatal confirmation in various tissues. By FISH it
      could be shown that every marker had a different origin.

PMID- 9259959
TI  - The human oocyte. Genetic aspects.
AB  - Since the beginning of in vitro fertilization (IVF), basic research has
      enlightened the field of human reproduction, especially in genetics. Indeed, the
      contribution of chromosomal anomalies to oocyte disorders and impaired
      developmental capacities of the embryos is now well known. Among oocytes that
      failed to fertilize after in vitro insemination, 26.5% were found to be abnormal
      comprising 13.3% hypohaploidy, 8.1% hyperhaploidy, 1.6% structural anomalies and
      3.5% diploidy. The total incidence of abnormalities seems to be correlated to the
      female status, and was found to be higher in oocytes from women with tubal or
      unexplained infertility than in those from women whose husband was infertile as a
      sole cause of couple infertility. Although few oocytes recovered during a natural
      cycle were studied, gonadotropins widely used to stimulate follicle growth and
      ovulation do not increase the risk of anomalies. The effect of maternal age on
      fetal aneuploidy, well documented at birth, has not yet be found unambiguously to
      be a consequence of an increased rate of aneuploid oocytes. Intra- and
      extrafollicular influences (perifollicular microvasculature, oxygenation, the
      presence of residues from cigarette smoke) are able to disturb maturation leading
      to immaturity and aneuploidy. To conclude, oocyte meiosis is very sensitive to
      endogenous or exogenous factors, which could lead to chromosomally abnormal
      oocytes and as a consequence, to abnormal zygotes.

PMID- 9259960
TI  - Congenital eye malformations in 212,479 consecutive births.
AB  - Congenital eye malformations were studied in a small geographical area in 212,479
      consecutive births. For each of the 145 new cases studied during the period 1979
      to 1994, more than 50 factors were compared in probands and in controls. The
      prevalence rate of congenital eye malformations was 6.8 per 10,000 for
      microphthalmia 1.7, anophthalmia 0.23, cataract 2.7 and coloboma 1.4
      respectively. Sex ratio was 0.82. Prenatal diagnosis was performed in 18 cases
      and 7 cases were induced abortions. The more common types of associated
      malformations in the 81 affected cases (53.8%) with at least one anomaly other
      than an eye malformation were clubfeet, microcephaly, hydrocephaly, cleft
      lip/palate and facial dysmorphia. At birth infants with eye malformations and
      other malformations were smaller, weighted less and their head circumference was
      lower than in controls. Placental weight was also lower than in controls.
      Pregnancies with eye malformations were more often complicated by threatened
      abortion, oligoamnios and polyhydramnios. Mothers of children with congenital eye
      malformations took more often drugs during pregnancy than mothers of controls.
      Fathers of children with congenital eye malformations were more often exposed to
      occupational hazards than fathers of controls. There was a significant
      association between eye malformations and consanguinity of parents. The
      recurrence risk for first degree relatives of probands was 8.9%. First degree
      relatives of probands had more than three times the prevalence of non-eye
      malformations than controls. These results are of relevance to genetic
      counseling.

PMID- 9259961
TI  - Has technology had an impact on survival in patients with recurrent colorectal
      cancer?

PMID- 9259962
TI  - Radioimmunoguided surgery benefits for recurrent colorectal cancer.
AB  - BACKGROUND: Despite new adjuvant therapy, 50% of patients with colon cancer will
      have recurrent disease. This study investigated the use of a radiolabeled
      monoclonal antibody in locating occult tumor during surgery for recurrent
      colorectal cancer. METHODS: Twenty-two patients with recurrent colorectal cancer
      underwent surgery using the radioimmunoguided surgery (RIGS) system. All patients
      were subjected to abdominal and chest computed tomography (CT). Before surgery,
      patients were injected with the CC49 monoclonal antibody (MoAb), anti-TAG
      antibody labeled with 125I. Ten patients with elevated carcinoembryonic antigen
      (CEA) levels and no CT findings had a scintigraphy scan with an anti-CEA MoAb
      labeled with 99Tc. Human antimouse antibody levels of these patients were within
      normal limits. Surgical exploration including liver ultrasound examination was
      followed by survey with a gamma-detecting probe (GDP). RESULTS: There was MoAb
      tumor localization in 100% of the patients. CT found nine tumor sites,
      traditional surgical exploration 30, and the GDP 51, with 44 confirmed by
      pathology (hematoxylin and eosin). The RIGS system found occult tumor in 10
      patients (45.4%) and resulted in major changes in surgical procedure in 11
      patients. In the 10 patients who had scintigraphy scans, 10 tumor sites were
      identified, whereas RIGS found an additional eight sites. CONCLUSION: RIGS
      technology offers a substantial benefit for patients undergoing surgery for
      recurrent colorectal cancer and a better chance of finding recurrent tumor
      intraoperatively in patients who have elevated CEA levels with no other CT
      findings.

PMID- 9259964
TI  - Carcinoma of the male breast: analysis of prognosis compared with matched female
      patients.
AB  - BACKGROUND: Considerable debate exists concerning the prognosis of breast cancer
      in male patients compared with that in female patients. Some studies have
      observed worse prognosis for men; others suggested the higher mortality rates
      were primarily due to delayed diagnosis. METHODS: Survival time from diagnosis
      with invasive disease to death resulting from breast cancer of 58 men treated
      between 1973 and 1989 was compared with survival of 174 women treated between
      1976 and 1978 who were matched by stage of disease and age at diagnosis. All
      patients were treated by mastectomy and axillary dissection. RESULTS: Tumors were
      < or = 2 cm in 70% of cases and 55% were free of axillary metastases. The
      histology of the tumors differed significantly by gender (p < 0.05).
      Significantly more men had estrogen receptor-positive tumors (87%) than did women
      (55%, p < 0.001). Survival at 10 years was similar for male and female patients.
      Multivariate analysis controlling for tumor size, number of positive axillary
      lymph nodes, age at diagnosis, histology, and receptor status indicated no
      significant difference in survival of male compared with female patients.
      CONCLUSIONS: These data conflict with the conventional wisdom that breast cancer
      in men carries a worse prognosis than the disease in women. Although histology of
      the tumor and receptor status differed by gender, these factors did not have an
      impact on survival in these paired patients. Our data indicate that breast
      carcinoma in males is not biologically more aggressive than in females.

PMID- 9259963
TI  - Feasibility of postmastectomy radiation therapy after TRAM flap breast
      reconstruction.
AB  - BACKGROUND: Postoperative radiotherapy (PORT) has been shown to decrease
      locoregional failure rates in high-risk breast cancer patients following modified
      radical mastectomy. However, there had not been a study evaluating the effect of
      PORT in patients after transverse rectus abdominis myocutaneous (TRAM) flap
      breast reconstruction. Therefore, we evaluated flap viability, cosmetic results,
      and locoregional recurrence in patients who underwent TRAM flap reconstruction
      and PORT. METHODS: The charts of patients who had undergone modified radical
      mastectomy with TRAM flap reconstruction and PORT at our institution were
      reviewed. Patients were examined in the clinic and interviewed by telephone to
      evaluate their perceptions of the cosmetic result. RESULTS: PORT was delivered to
      19 patients with TRAM flaps (3 pedicled and 16 free flaps) between 1988 and 1994.
      There were no TRAM flap losses as a result of either surgical or radiotherapy
      complications. Two patients developed fat necrosis, one with a pedicled and one
      with a free TRAM flap. Patients with pedicled TRAM flaps noted more volume loss
      in the breast after radiation therapy. Eighty-four percent of patients felt their
      overall cosmetic result was excellent or good; only one patient reported a poor
      cosmetic result. Local control was achieved in three of the four patients who
      received PORT for local recurrence. There was only one local recurrence among the
      14 patients who received PORT because they were at high risk of local recurrence.
      CONCLUSIONS: These results suggest that PORT can be given safely to high-risk
      patients following TRAM flap breast reconstruction with excellent cosmetic
      results and good locoregional control.

PMID- 9259965
TI  - Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine)
      carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with a
      propensity for local recurrence, regional and distant metastases. There are no
      well-defined prognostic factors that predict behavior of this tumor, nor are
      treatment guidelines well established. METHODS: Staging of patients with a new
      diagnosis of MCC was attempted using selective lymphadenectomy concurrent with
      primary excision. Preoperative and intraoperative mapping, excision, and thorough
      histologic evaluation of the first lymph node draining the tumor primary site
      [sentinel node] was performed. Patients with tumor metastasis in the sentinel
      node underwent complete resection of the remainder of the lymph node basin.
      RESULTS: Twelve patients underwent removal of 22 sentinel nodes. Two patients
      demonstrated metastatic disease in their sentinel lymph nodes, and complete
      dissection of the involved nodal basin revealed additional positive nodes. The
      node-negative patients received no further surgical therapy, with no evidence of
      recurrent local or regional disease at a maximum of 26 months follow-up (median
      10.5 months). CONCLUSIONS: While the data are preliminary and initial follow-up
      is limited, early results suggest that sentinel lymph node mapping and excision
      may be a useful adjunct in the treatment of MCC. This technique may identify a
      population of patients who would benefit from further surgical lymph node
      excision.

PMID- 9259966
TI  - Computed tomography in staging of patients with melanoma metastatic to the
      regional nodes.
AB  - BACKGROUND: This study addresses the yield and clinical impact of computed
      tomography (CT) imaging in otherwise asymptomatic patients with stage III
      melanoma metastatic to the regional nodes. METHODS: The database from the
      University of Michigan Mutlidisciplinary Melanoma Clinic was reviewed and
      identified 127 asymptomatic patients with stage III melanoma (regional nodal
      disease) who received CT scans of the head, chest, abdomen, and/or pelvis. Scans
      were confirmed as true positive, false positive, and normal. RESULTS: Four
      hundred twenty-six head and body CT scans were performed at the time of
      presentation of stage III disease. Twenty patients had a true-positive CT scan
      revealing unsuspected metastases. Fifteen patients had abnormal CT scans
      subsequently shown to be a benign process or second malignancy. The incidence of
      true-positive CT scans was not different between the groups of patients who had
      clinically apparent versus occult nodal disease. There was a significantly higher
      incidence of abdominal and pelvic metastatic sites identified by CT scan in
      patients with inguinal nodal disease compared with axillary or head and neck node
      positive patients. CONCLUSIONS: The yield of detection of unsuspected metastases
      by CT scans in asymptomatic patients with stage III melanoma was not
      insignificant. Because patients with resected stage III disease are recommended
      to have adjuvant interferon-alpha for 1 year, CT staging plays an important role
      in identifying appropriate candidates for treatment. The toxicity of interferon
      alpha therapy is not insignificant. The value of routine CT in asymptomatic
      patients with nodal metastasis deserves further prospective study.

PMID- 9259967
TI  - Surgical management of thyroid cancer invading the airway.
AB  - BACKGROUND: Locally advanced thyroid cancer invading the tracheal cartilage
      represents a difficult treatment dilemma during thyroidectomy. METHODS: A
      retrospective chart review was performed to determine the results of
      laryngotracheal resection or tracheal cartilage shave with adjuvant radiotherapy
      in patients with locally advanced thyroid cancer invading the upper airway.
      RESULTS: Of 597 patients undergoing thyroidectomy for thyroid cancer, 40 were
      found to have laryngotracheal invasion. Thirty-five patients with superficial
      invasion underwent cartilage shave procedures with adjuvant radiotherapy; five
      with full-thickness invasion underwent radical resection, including tracheal
      sleeve resection (n = 3) or total laryngectomy (n = 2). Histologic subtypes
      included papillary (n = 32), follicular (n = 2), Hurthle cell (n = 1), medullary
      (n = 3), and anaplastic (n = 2). Of the cartilage shave group, 25 are currently
      alive with no evidence of disease at a mean follow-up of 81 months (range 1-290).
      Six developed isolated local/regional recurrence and were managed with total
      laryngectomy (n = 1), tracheal resection (n = 1), cervical lymphadenectomy (n =
      1), or repeat radiotherapy (n = 3). All six patients remain free of disease at a
      mean follow-up of 5 years. Of those who underwent initial laryngotracheal
      resection, four remain free of disease at a mean follow-up of 5 years. The rates
      of 10-year disease-free survival and overall survival for all patients were 47.9%
      (95% confidence interval [CI] 24.8, 71.0) and 83.9% (95% CI 70.3, 97.5),
      respectively. CONCLUSIONS: These data suggest that adequate management of thyroid
      cancer with laryngotracheal invasion can be achieved with a more conservative
      surgical approach and adjuvant radiotherapy, reserving more radical resections
      for extensive primary lesions or locally recurrent disease.

PMID- 9259968
TI  - Pleural lavage cytology immediately after thoracotomy and before closure of the
      thoracic cavity for lung cancer without pleural effusion and dissemination:
      clinicopathologic and prognostic analysis.
AB  - BACKGROUND: The significance of intraoperative pleural lavage cytology (PLC) in
      lung cancer patients without malignant effusion remains undetermined in terms of
      staging, prognosis, and local management. METHODS: PLC was performed both after
      thoractomy and before closure of the thoracic cavity in 325 patients with lung
      cancer without malignant pleurisy. RESULTS: According to the PLC results
      (positive [+] or negative [-] after thoracotomy/before closure), the patients
      were classified as follows: group A (-/-), 262 patients; group B (+/-), 19; group
      C (-/+), 22; and group D (+/+), 22. In comparison with group A, group C showed
      more advanced stage with aggressive nodal involvement, and group D showed more
      advanced lung cancer related to pleural and nodal involvement, whereas group B
      showed characteristics similar to those of group A. The rate of pleural
      recurrence in group D was the highest (26%). In particular, pleural recurrence
      was seen in the patients with a relatively large number of adenocarcinoma cells
      in PLC after thoractomy. The patients in groups C and D, especially those with
      adenocarcinoma, showed poorer prognosis, but in a multivariate analysis, PLC
      status was not an independent prognostic factor. CONCLUSIONS: PLC status after
      thoractomy provides useful information in the detection of high-risk subgroup for
      pleural recurrence. Although PLC status is closely associated with survival, its
      prognostic value is not independent.

PMID- 9259969
TI  - Absence of p16 gene (CDKN2) deletions in microdissected primary breast carcinoma
      specimens.
AB  - BACKGROUND: The p16 gene (CDKN2), a tumor suppressor gene located on chromosome
      9p21, has been demonstrated to be mutated or deleted with high frequency in a
      variety of tumor cell lines, including breast. While previous studies have not
      demonstrated CDKN2 mutations in primary breast carcinomas, it is possible that
      gene deletion in neoplastic DNA was marked by the presence of contaminating
      normal stromal DNA in breast carcinoma specimens. METHODS: We investigated the
      incidence of homozygous deletion of CDKN2 by analyzing 20 microdissected pure
      populations of primary breast carcinoma cells. Using polymerase chain reaction
      (PCR) techniques, the entire coding region and intervening introns of CDKN2 were
      amplified. The PCR products were resolved by agarose gel electrophoresis and
      single-strand conformation polymorphism (SSCP) analysis. RESULTS: We detected no
      deletions or mutations of the p16 gene. CONCLUSIONS: CDKN2 is not deleted with
      high frequency in primary breast carcinomas, and the p16 gene does not play a
      role in breast carcinogenesis via this mechanism.

PMID- 9259970
TI  - Nephrectomy during operative management of retroperitoneal sarcoma.
AB  - BACKGROUND: Complete resection of a retroperitoneal sarcoma often requires
      removal of adjacent organs. In this study we evaluated the role of nephrectomy
      during operation for retroperitoneal sarcoma. METHODS: Between July 1982 and July
      1995, 75 of the 371 (20%) patients who underwent resection of retroperitoneal
      sarcoma at MSKCC underwent concommitant nephrectomy. Data concerning the reasons
      for nephrectomy, degree of sarcomatous renal involvement, and survival were
      retrospectively analyzed. RESULTS: Fifty-four patients (72%) underwent
      nephrectomy during the initial resection, and 21 (28%) during a resection of a
      recurrent or persistent tumor. The most common reason for nephrectomy was total
      encasement by sarcoma (n = 40; 53%), followed by dense adherence of the tumor to
      the kidney (n = 21; 28%), and the direct invasion of the kidney by tumor (n = 2;
      3%). Pathology demonstrated an absence of kidney invasion in the majority of
      cases (55 of 75; 73%). Renal capsular invasion was present in 11 of 75 (15%),
      renal parenchymal invasion in 7 of 75 (9%), and renal vein invasion in 2 of 75
      (3%) of cases. There were no significant differences in survival based on degree
      of sarcoma involvement of the kidney, tumor grade, or whether the resection was
      for primary or recurrent disease. The 53 patients who underwent a complete gross
      resection of all tumor had a significantly improved long-term survival compared
      to the 20 patients who did not (50% versus 20% DFS at 5 years, respectively; p <
      0.001). CONCLUSIONS: Decisions for concomitant nephrectomy during resection of
      retroperitoneal sarcoma should be based on whether this maneuver will provide a
      complete resection of all gross tumor, in which case the long-term disease-free
      survival of 50% is comparable to the reported 5-year survival of all patients
      with retroperitoneal sarcoma who are completely resected.

PMID- 9259972
TI  - Expansion of CD3+CD56+ lymphocytes correlates with induction of cytotoxicity by
      interleukin-2 gene transfer in human breast tumor cultures.
AB  - BACKGROUND: Mice immunized with murine mammary carcinoma cells genetically
      engineered to secrete interleukin-2 (IL-2) are rendered resistant to subsequent
      challenge with unmodified tumor cells, and in the case of mice bearing
      established tumors, the rate of development of pulmonary metastases is reduced.
      Despite these encouraging animal results, little is known about the induction of
      antitumor immunity by IL-2 gene transfer in human breast cancer. METHODS:
      Adenovirally mediated IL-2 gene transfer was performed in 12 tumor fragment
      cultures established from seven primary breast cancers. Autologous tumor
      infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs)
      were cocultured with transduced tumor fragments, and changes in phenotype and
      cytotoxicity were measured. RESULTS: IL-2 was never detectable in the
      untransduced cultures, but it peaked at 5.0-1,324.8 ng/ml in the transduced
      cultures. Lymphocyte counts declined in all untransduced cultures, but they
      increased two- to sevenfold in four transduced cultures. CD4:CD8 ratios decreased
      from a mean of 2.11 at baseline to 1.27 after stimulation in coculture (p =
      0.03). Expansion of lymphocytes expressing the natural killer cell phenotype (CD3
      CD56+) occurred in only one culture, but the CD3+CD56+ population increased in
      four of six cultures. Lymphocytes from four of 10 cocultures generated
      significant cytotoxicity against allogeneic breast cancer cells. Induction of
      cytotoxicity correlated with expansion of the CD3+CD56+ phenotype (R2 = 0.805, p
      = 0.02). CONCLUSIONS: IL-2 gene expression by human breast cancer causes
      expansion of CD3+CD56+ cytotoxic-lymphocytes. This phenotype is consistent with
      that of a non-major histocompatibility complex (MHC)-restricted cytokine induced
      killer cell population previously described.

PMID- 9259974
TI  - Isotopic biogeochemistry as a marker of Neandertal diet.
AB  - Natural abundances in 13C and 15N of bone collagen are linked to those of the
      diet. This isotopic signal can thus be linked to the dietary parameters of a
      given individual, such as the plants at the beginning of his food web and his
      position in the trophic web. In order to use this approach to study the diet of
      ancient humans, it is crucial to be sure that the original isotopic abundances of
      fossil collagen are preserved. This is done by controlling the biochemical purity
      of the organic matter extracted from fossil bones, and by checking that the
      isotopic differences observed in modern environments between herbivorous and
      carnivorous species are indeed measured in the fossil samples. Upper Pleistocene
      sites with a good isotopic preservation of collagen have been recognized in
      temperate and arctic environments. The isotopic signatures measured in such sites
      highlight particularities of the "mammoth steppe" fauna, and improve our
      knowledge of the diet of Neandertals.

PMID- 9259971
TI  - Core needle biopsy for diagnosis of extremity soft tissue sarcoma.
AB  - BACKGROUND: Classic teaching has advocated the use of open biopsy to diagnose and
      grade extremity soft-tissue sarcoma. Reported advantages of core needle biopsy
      include the minimal morbidity, cost, and time. The perceived disadvantage has
      been diagnostic inaccuracy. The objective of this study was to compare the
      diagnostic accuracy of core needle biopsy to incisional or frozen section biopsy
      for primary extremity masses suspicious for soft-tissue sarcoma. METHODS:
      Patients presenting with extremity masses were identified from our prospective
      soft-tissue sarcoma database (malignant) and from the clinical information center
      (benign) between January 1, 1990, and December 31, 1995. Biopsy and subsequent
      resection data were collected from the pathologic records. RESULTS: During this
      time, 164 primary extremity soft-tissue masses were evaluated before any biopsy.
      As the initial diagnostic approach, there were 60 core needle, 44 incisional, 36
      frozen section, and 26 excisional biopsies. Two patients underwent two biopsy
      procedures. Ninety-three percent of the specimens obtained at core needle biopsy
      were adequate to make a diagnosis. Of the adequate core needle biopsy specimens,
      95%, 88% and 75% correlated with the final resection diagnosis for malignancy,
      grade, and histologic subtype, respectively. Of the frozen section biopsy
      specimens, 94% were adequate, and accurate diagnostic results of malignancy were
      obtained with 88%. However, only 62% and 47% were correct for grade and
      histologic subtype, respectively, which was significantly different than the
      results obtained with incisional biopsy. The false-negative and false-positive
      rates for core needle biopsy were 5% and 0% for malignancy. Two core needle
      biopsy specimens graded low were found to be high, and one core needle biopsy
      specimen graded high was subsequently found to be low on final resection.
      CONCLUSIONS: When read by an experienced pathologist, the results of core needle
      biopsy provide accurate diagnostic information for malignancy and grade. Adequate
      core needle biopsy obviates the need for open biopsy and can be used for rational
      treatment planning. In the absence of adequate tissue, open biopsy is required.

PMID- 9259973
TI  - Mortality, major amputation rates, and leukopenia after isolated limb perfusion
      with phenylalanine mustard for the treatment of melanoma.
AB  - BACKGROUND: Isolated limb perfusion (ILP) is a treatment for cutaneous melanoma
      performed by several centers worldwide. The final data analysis of the World
      Health Organization and European Organization for Research and Treatment of
      Cancer in the use of ILP as adjuvant treatment for cutaneous melanoma is pending.
      ILP is effective to treat recurrent cutaneous melanoma. We determined the
      published rates of morbidity and mortality of ILP and put that component of the
      procedure into contemporary perspective. METHODS: A MEDLINE search was conducted
      of the English-language literature from 1980 to 1995 for all publications
      reporting perfusion with phenylalanine mustard alone or combined with other
      agents. Patients treated by staged perfusion or fractional doses of chemotherapy
      were excluded. All published series were analyzed for the rate of mortality,
      number of major amputations, and presence of leukopenia. RESULTS: The 30-day
      mortality rate for > 2,000 patients was 0.6%. Death often resulted from
      cardiopulmonary complications or overwhelming sepsis from leukopenia. Leukopenia
      occurred in 0.7% of patients reviewed, caused by leakage of chemotherapeutic
      agents into the systemic circulation. Major amputations occurred in 0.8% of
      patients, and most were of the lower extremity. CONCLUSIONS: The definition of
      efficacy of ILP in the treatment of extremity melanomas remains to be clearly
      defined. However, based on this review of worldwide publications, the risk of
      death, amputation, and leukopenia is low.

PMID- 9259975
TI  - Molecular preservation and isotopy of Mesolithic human finds from the Ofnet cave
      (Bavaria, Germany).
AB  - Favourable burial conditions and self-limiting decomposition processes led to an
      extraordinarily well molecular preservation of the Mesolithic human skull finds
      from the Ofnet cave (district Nordlingen, Bavaria). Beyond the extraction of bone
      collagen, a selection of serum proteins from bone was identified immunologically.
      Stable carbon and nitrogen isotope ratios from collagen gave clues to dietary
      behaviour including nursing practices. Diverging results after the application of
      biochemical protocols (for protein cleaning) and biophysical methods (for stable
      isotope analysis) are of particular interest: while the first approach failed to
      quantitatively eliminate anorganic contaminations, the second left some organic,
      exogenous residues in the samples. Thus, methods for protein extraction must vary
      according to problem solution and ultimate aim of the study. Taking this into
      account, application of invasive methods is also encouraged to rare and valuable
      skeletal finds.

PMID- 9259976
TI  - Science and medicine at the millennium.

PMID- 9259977
TI  - Structure-function relationships of the PEA3 group of Ets-related transcription
      factors.
AB  - The PEA3 group of transcription factors belongs to the Ets family and is composed
      of PEA3, ERM, and ER81, which are more than 95% identical within the DNA-binding
      domain--the ETS domain--and which demonstrate 50% aa identity overall. We present
      here a review of the current knowledge of these transcription factors, which
      possess functional domains responsible for DNA-binding, DNA-binding inhibition,
      and transactivation. Recent data suggest that these factors are targets for
      signaling cascades, such as the Ras-dependent ones, and thus may contribute first
      to the nuclear response to cell stimulation and second to Ras-induced cell
      transformation. The expression of the PEA3 group members in numerous developing
      murine organs, and, especially, in epithelial-mesenchymal interaction events,
      suggests a key role in murine organogenesis. Moreover, their expression in
      certain breast cancer cells suggests a possible involvement of these genes in the
      appearance, progression, and invasion of malignant cells.

PMID- 9259978
TI  - New physiological importance of two classic residual products: carbon monoxide
      and bilirubin.
AB  - Heme oxygenase the rate-limiting step in the degradation of heme to bilirubin,
      generates carbon monoxide. This gaseous molecule plays important roles in
      neuronal signaling and modulation of vascular tone. Additionally, carbon monoxide
      is involved in some pathological conditions (e.g., ischemia, endotoxic shock,
      excitotoxicity) as a protective or toxic factor. Bilirubin, another heme
      metabolite, exhibits intriguing biological activities as an antioxidant, an
      antimutagen, and an anti-complement agent. Vital functions and the dual nature
      displayed by these two heme metabolites are discussed.

PMID- 9259979
TI  - An evaluation of the use of dried blood spots from newborn screening for
      monitoring the prevalence of cocaine use among childbearing women.
AB  - A collaborative March of Dimes study was designed to examine the utility of dried
      blood spot (DBS) materials routinely collected from newborns as a source for
      monitoring cocaine exposure and to assess the prevalence of cocaine use among
      childbearing women in Georgia. We used a modified urinary radioimmunoassay (RIA)
      to anonymously detect the cocaine metabolite benzoylecgonine (BE) in DBSs.
      Extensive efforts were undertaken to assure absolute nonlinkage of BE data to any
      individual. The positive results found by RIA were confirmed by a mass
      spectrometry (MS) method specifically developed to detect BE in DBSs. BE was
      measured in 23,141 DBSs collected during 2 months of routine newborn screening in
      Georgia. A good correlation was observed for RIA results versus MS results (r2 =
      0.97). The estimated minimal statewide BE prevalence was 4.8 per 1000
      childbearing women. We demonstrated that immunoassay testing for cocaine without
      confirmatory testing can yield falsely elevated prevalence rates. When proper
      confirmatory testing is done, DBSs are a valuable source for population-based
      monitoring of substance abuse among childbearing women.

PMID- 9259980
TI  - Increased inducible nitric oxide synthase in skeletal muscle biopsies from
      patients with chronic heart failure.
AB  - In addition to left ventricular pump failure and low cardiac output, structural
      and metabolic alterations of skeletal muscle are thought to contribute to
      exercise intolerance seen in patients with CHF. Studies using cardiac myocytes
      have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS)
      as a potential agent associated with the genesis of dilated cardiomyopathy. The
      present study was designed to locate iNOS in the working skeletal muscle of
      patients with congestive heart failure. Specific antibodies were used to detect
      iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of
      37 patients with left ventricular pump failure and 8 normal controls. The
      expression was restricted to skeletal muscle myocytes and was increased five- to
      ninefold in patients with chronic heart failure. There was no statistically
      significant difference in iNOS expression between patients with dilated
      cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally
      increased expression of iNOS and the experimental evidence that NO attenuates the
      contractile performance of the skeletal muscle suggest that the expression of
      iNOS may be responsible for the exercise intolerance seen in patients with
      chronic heart failure.

PMID- 9259981
TI  - Abnormal metabolism of mannose in families with carbohydrate-deficient
      glycoprotein syndrome type 1.
AB  - Patients with carbohydrate-deficient glycoprotein syndrome (CDGS) Type 1
      underglycosylate many glycoproteins by failing to add entire N-linked
      carbohydrate chains to them. The primary defect in these patients has been
      reported as a > 90% deficiency in phosphomannomutase activity (PMM), the enzyme
      that converts mannose-6-phosphate to mannose-1-phosphate. This lesion reduces
      both the amount and the size of the lipid-linked oligosaccharide precursor. We
      have now analyzed the activity of PMM and the level of glycosylation in cultured
      fibroblasts as well as the level of blood mannose in seven CDGS Type 1 patients
      and their parents. All of these patients were approximately 95% deficient in PMM
      activity and their parents had an average of 51% of control PMM activity.
      Furthermore, parental fibroblasts showed reduced glycosylation and a higher
      proportion of truncated N-linked chains compared to those made by control
      fibroblasts. Addition of 0.25 mM mannose to the culture medium corrected both the
      underglycosylation and size of the oligosaccharide chains in CDGS Type 1 patients
      and their parents. Finally, serum from CDGS patients had considerably reduced
      mannose levels (5-40 microM) compared to normal controls (40-80 microM) and some
      parents were below normal (16-103 microM). These results suggest that the reduced
      blood mannose level is a consequence of the PMM deficiency. This is the first
      inherited disorder in human metabolism that shows a decrease in available
      mannose. Increasing blood mannose levels might correct some protein
      underglycosylation in these patients.

PMID- 9259983
TI  - Acidic FGF regulation of hyperproliferation of fibroblasts in human autosomal
      dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cystic
      tubule enlargement and expansion of the interstitium associated with fibrosis.
      Our previous studies have analyzed the increased proliferation of cystic
      epithelial cells and this study examines the basis of increased proliferation of
      interstitial fibroblasts associated with ADPKD disease progression. ADPKD
      fibroblasts show phenotypic alterations in vitro, have acquired the capacity to
      grow in soft agar, and show an increased mitogenic response to a variety of
      growth factors particularly acidic FGF (aFGF). ELISA, Western immunoblot
      analysis, and immunocytochemistry showed increased aFGF content in ADPKD tissues
      and fibroblasts in culture, and aFGF was secreted into the extracellular matrix
      and conditioned medium, respectively. No alterations in aFGF receptor number were
      found, but Scatchard analysis of 125I-aFGF binding suggested an increased
      affinity of binding to the low affinity receptor, and covalent cross-linking
      analysis suggested the presence of novel putative receptors (120 kDa) in ADPKD
      fibroblasts. Signaling abnormalities were found, since aFGF incubation resulted
      in the tyrosine phosphorylation of additional substrates, more rapidly and for a
      more sustained duration in ADPKD fibroblasts than in normal fibroblasts. These
      findings suggest an important role for acidic FGF in the hyperproliferation of
      interstitial fibroblasts associated with disease progression in human ADPKD.

PMID- 9259984
TI  - Transcription of the amylin gene in newborn dogs.
AB  - To understand the role of amylin, the novel pancreatic hormone, in fuel
      metabolism of neonatal mammals, the transcription of the amylin gene in newborn
      dogs was studied under different conditions, such as fasting, hyperinsulinemia,
      and hyper IGF-1. Our results showed (1) The amylin mRNA level decreased during a
      24-h fasting period after birth, 59.1 +/- 4.5% at 4 h, 80.1 +/- 7.9% at 10 h, and
      44.5 +/- 3.0% at 24 h, compared to 0-h-fasted controls, respectively. In this
      period, the decreased mRNA level of the amylin gene and the increased mRNA levels
      of the gluconeogenic genes showed an inverse ratio relationship. (2) Euglycemic
      hyperinsulinemic clamp did not alter the amylin mRNA level, 39.6 +/- 1.2%
      (hyperinsulinemia) vs 41.4 +/- 3.1% (controls), in newborn dogs, but lowered the
      amylin mRNA by 35.3%, 64.7 +/- 12.5% vs 100.0 +/- 12.0%, in adult dogs. (3)
      Euglycemic hyper-IGF-1 clamp had no effect on the amylin mRNA levels of either
      newborn or adult dogs, 52.4 +/- 9.1% (hyper IGF-1) vs 47.9 +/- 4.3% (controls) in
      newborns and 95.2 +/- 12.6% (hyper IGF-1) vs 100.0 +/- 14.0% (controls) in
      adults. The data from the present study showed that amylin may be involved in
      carbohydrate homeostasis, but may not be able to stimulate gluconeogenesis in
      newborn dogs during a 24-h fasting period after birth. Whether amylin action may
      be another mechanism for neonatal hyperglycemia by inducing insulin resistance in
      peripheral tissues needs further investigation.

PMID- 9259982
TI  - Isolation and nucleotide sequence of canine glucose-6-phosphatase mRNA:
      identification of mutation in puppies with glycogen storage disease type Ia.
AB  - Two Maltese puppies with massive hepatomegaly and failure to thrive had isolated
      deficient glucose-6-phosphatase (G-6-Pase) activity in liver and kidney and
      pathological findings compatible with GSD-Ia. To identify the mutation, we cloned
      G-6-Pase canine cDNA by RT-PCR with primers from the murine G-6-Pase gene
      sequence. The canine G-6-Pase cDNA is 2346 bp, with a 5' untranslated region of
      87 bp, a coding region of 1071 bp, and a 3' untranslated region of 1185 bp. The
      difference between the canine and human sequences is in the 3' untranslated
      region. A greater than 90% amino acid sequence homology was seen with canine,
      human, murine, and rat G-6-Pase. G-6-Pase cDNA from affected and control puppies
      revealed complete homology except at nt position 450, which showed a guanine to
      cytosine (G to C) transversion resulting in substitution of a methionine by
      isoleucine at codon 121 (M121I) in all five clones studied. The loss of an NcoI
      restriction site on genomic DNA amplified with primers flanking the mutation
      allowed us to prove that affected puppies were homozygous for the mutation and
      parents were heterozygous carriers. The mutant G-6-Pase cDNA had 15 times less
      enzyme activity than wild-type cDNA following transient transfection. Northern
      blot analysis of puppies with GSD-Ia revealed increased G-6-Pase mRNA, compared
      to normal controls. Increased G-6-Pase mRNA was also seen in normal fasted
      puppies compared to littermates in the fed state, suggesting that the increased G
      6-Pase mRNA is a physiologic response to fasting. This is the first report of a
      molecularly confirmed naturally occurring animal model of GSD-Ia. The
      establishment of a breeding colony of this dog strain will facilitate studies on
      the role of G-6-Pase gene in glucose homeostasis, in pathophysiology of disease,
      and development of novel therapeutic approaches such as gene therapy.

PMID- 9259985
TI  - Biochemical features of a patient with Zellweger-like syndrome with normal PTS-1
      and PTS-2 peroxisomal protein import systems: a new peroxisomal disease.
AB  - The peroxisomal disorders represent a group of inherited metabolic disorders that
      derive from defects of peroxisomal biogenesis and/or from dysfunction of single
      or multiple peroxisomal enzymes. We described earlier an 8 1/2 year-old with a
      history of progressive developmental delay, micronodular cirrhosis, and elevated
      very long chain fatty acids in plasma and skin fibroblasts. These findings were
      felt to be compatible with both neonatal adrenoleukodystrophy (nALD) and
      Zellweger syndrome (ZS). This patient is now 21 years old and his clinical
      course, inconsistent with either nALD or ZS, led us to examine his peroxisomal
      status in light of a possible new peroxisomal disease. The normal levels of bile
      acid precursors found in this patient suggest that peroxisomal beta-oxidation is
      functional. The activities of dihydroxyacetone phosphate acyltransferase and
      oxidation of lignoceric acid and phytanic acid were 14, 17, and 15% of the
      control, respectively. This partial activity for oxidation and the normal levels
      of bile acid precursors suggests that this patient has peroxisomes containing
      beta-oxidation enzymes. Western blot analysis of subcellular organelles showed
      that beta-oxidation enzyme proteins are present at normal levels in catalase
      negative peroxisomes of density equivalent to normal peroxisomes. The presence of
      acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in catalase-negative peroxisomes
      suggests that both peroxisomal targeting signal-1 (PTS-1), and peroxisomal
      targeting signal-2 (PTS-2)-mediated protein transport processes into peroxisomes
      are normal in this patient. These findings of catalase-negative peroxisomes of
      normal density and normal PTS-1 and PTS-2 import machinery with partial
      peroxisomal functions clearly demonstrate that this patient differs from those
      with known disorders of peroxisomal biogenesis.

PMID- 9259986
TI  - Comparative analysis of apo(a) gene alleles: distribution of pentanucleotide
      repeats in position -1373 and C/T transition in position +93 among patients with
      myocardial infarction and a control group in St. Petersburg, Russia.
AB  - To evaluate whether polymorphisms in the 5' region of the apolipoprotein(a) gene
      alter the risk for myocardial infarction, 289 Russian male patients with
      myocardial infarction (MI) and 284 subjects in a control group were investigated
      regarding the distribution of pentanucleotide repeats (PNRs) at position -1373
      and a C/T transition at position +93. For detection of the C/T (+93) allele, we
      developed a rapid, nonisotopic method by mismatch PCR-mediated site-directed
      mutagenesis and restriction enzyme digestion. We observed significant differences
      in prevailing alleles with over eight (TTTTA) repeats among MI patients,
      including those with MI younger than 55 years of age. We observed the prevalence
      of the T (+93) allele in children without a family history of CHD compared to
      young MI patients. These findings support the notion that PNR alleles with over
      eight (TTTTA) repeats may play a pathogenic role, and the T (+93) allele may have
      a protective effect for the inherited predisposition to heart disease.

PMID- 9259987
TI  - Isolation and partial characterisation of insulin-mimetic inositol phosphoglycans
      from human liver.
AB  - Extracts of human liver were found to contain activities which copurified and
      coeluted with the two major subtypes of mediators (type A and type P) isolated
      from insulin-stimulated rat liver. The putative type A mediator from human liver
      inhibited cAMP-dependent protein kinase from bovine heart, decreased
      phosphoenolypyruvate carboxykinase mRNA levels in rat hepatoma cells, and
      stimulated lipogenesis in rat adipocytes. The putative type P mediator stimulated
      bovine heart pyruvate dehydrogenase phosphatase. Both fractions were able to
      stimulate proliferation of EGFR T17 fibroblasts and the type A was able to
      support growth in organotypic cultures of chicken embryo cochleovestibular
      ganglia. Both activities were resistant to Pronase treatment and the presence of
      carbohydrates, phosphate, and free-amino groups were confirmed in the two
      fractions. These properties are consistent with the structure/ function
      characteristics of the type A and P inositolphosphoglycans (IPG) previously
      characterized from rat liver. Further, the ability of the human-derived mediators
      to interact with rat adipocytes and bovine-derived metabolic enzymes suggests
      similarity in structure between the mediators purified from different species.
      Galactose oxidase-susceptible membrane-associated glycosylphosphatidylinositols
      (GPI) have been proposed to be the precursors of IPG. GPI was purified from human
      liver membranes followed by treatment with galactose oxidase and reduction with
      NaB3H4. Serial t.l.c. revealed three radiolabeled bands which comigrated with the
      putative GPI precursors found in rat liver. These galactose-oxidase-reactive
      lipidic compounds, however, were only partially susceptible to hydrolysis with
      phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis and
      were resistant to glycosylphosphatidylinositol-specific phospholipase C from
      Trypanosoma brucei. These data indicate that IPG molecules with insulin-like
      biological activities are present in human liver.

PMID- 9259988
TI  - Asymmetrical labeling of D-glucose generated from [3(-13)C]pyruvate in rat
      hepatocytes.
AB  - The generation of 13C-labeled D-glucose isotopomers by rat hepatocytes incubated
      for 30 or 120 min in the presence of 10 mM [3-(13)C]pyruvate was assessed by 13C
      NMR. The amount of C1-labeled D-glucose exceeded that of C2-labeled hexose, which
      was itself higher than that of C3-labeled D-glucose. A comparable hierarchy was
      observed in the C6-C5-C4 moiety of the hexose. The latter moiety of D-glucose was
      more efficiently labeled, however, than the C3-C2-C1 moiety. This finding is
      similar to that both previously reported and again observed in the present study
      when hepatocytes were exposed to [2(-13)C]pyruvate. These converging observations
      thus support the concept of enzyme-to-enzyme channeling of D-glyceraldehyde 3
      phosphate between glyceraldehyde-3-phosphate dehydrogenase and phospho
      fructoaldolase.

PMID- 9259989
TI  - Preliminary investigation of the use of dried-blood spots for the assessment of
      in utero exposure to environmental pollutants.
AB  - We determined the concentration of dichlorodiphenyldichloroethylene (p,p'-DDE) in
      dried-blood spot specimens from 2-day-old infants from rural Texas who had never
      been breast fed. Anonymous, residual whole blood spots on filter paper,
      previously used for routine newborn screening procedures, were soaked in a
      phosphate buffer, extracted with an organic solvent, and eluted through silica
      gel. The concentrated eluates were analyzed by capillary gas chromatography with
      electron capture detection (ECD). The blood collected from 10 newborns was
      analyzed and found to contain DDE concentrations ranging from 0.13 to 1.87
      pg/microliter with a mean of 0.72 pg/microliter. One of the 10 newborns had a
      whole blood DDE concentration of 1.87 pg/microliter, which was greater than the
      concentration of 1.34 pg/microliter in a freshly drawn sample from an adult donor
      whose blood serum was shown to contain DDE. With improvement in detection limits,
      this approach has the potential to displace the analyses of mothers' blood (as a
      surrogate indicator of infants' exposures) and cord blood as standard procedures
      for determining the newborns' body burden of environmental pollutants.

PMID- 9259990
TI  - Endogenous and exogenous antioxidants and the generation of antigenic epitopes in
      oxidatively-modified LDL.

PMID- 9259991
TI  - Whole plasma oxidation assay as a measure of lipoprotein oxidizability.
AB  - Lipoprotein oxidation induced in vitro in whole plasma is expected to be a more
      relevant model of the lipoprotein oxidation in the arterial wall than the in
      vitro oxidation of single isolated lipoproteins, e.g., low density lipoprotein
      (LDL). However, it is unclear, whether the oxidizability of whole plasma may
      serve as an adequate measure of the oxidizability of plasma lipoproteins. We
      measured the oxidizability of whole plasma diluted 150-fold as an absorbance
      increase at 234 nm known to reflect the level of conjugated dienes in the
      samples. Plasma oxidation was induced by Cu(II), 2,2'-azobis-(2-amidinopropane)
      hydrochloride (AAPH), lipoxygenase or myeloperoxidase+H2O2. Oxidizability of
      human plasma measured in the presence of Cu(II) was found to correlate with the
      oxidizability of LDL measured in the common Cu(II)-based LDL oxidation assay. The
      plasma oxidizability also correlated positively with plasma oxidizable fatty acid
      and negatively with plasma antioxidant content. Supplementation of human plasma
      with different antioxidants (albumin, urate, ascorbate, bilirubin, alpha
      tocopherol and ubiquinol-10) in vitro decreased its oxidizability.
      Supplementation of Watanabe heritable hyperlipidaemic rabbits with different
      antioxidants (vitamin E, ubiquinone-10, probucol, carvedilol) in vivo lowered the
      oxidizability of rabbit plasma in comparison with rabbits fed standard diet. When
      plasma from hyperlipidaemic patients with or without coronary heart disease and
      from age-matched healthy controls was studied, the plasma oxidizability was found
      to be highest in the patients with coronary heart disease and lowest in the
      controls. Taken together, these data indicate that the plasma oxidation assay (i)
      provides information similar to that obtained using the common LDL oxidation
      assay, (ii) upgrades the latter, taking into account the effect of hydrophilic
      antioxidants on lipoprotein oxidation and characterizing the oxidizability of all
      plasma lipoproteins, and (iii) offers important practical advantages, such as
      fast and simple sample processing, low amount of plasma required and avoidance of
      artefactual oxidation during lipoprotein isolation. We propose the measurement of
      plasma oxidizability at 234 nm as an adequate practical index of the
      oxidizability of plasma lipoproteins.

PMID- 9259992
TI  - The role of oxidative stress in the long-term glycation of LDL.
AB  - Advanced glycation is a major pathway for the posttranslational modification of
      plasma and tissue proteins. The initiating reaction is the nonenzymatic addition
      of sugars such as glucose to the primary amino groups of proteins, i.e., mainly
      to lysine residues. These "early" Schiff base and Amadori products then undergo a
      series of inter- and intramolecular rearrangements to produce the "late" products
      termed advanced glycation end products (AGEs). Incubation of LDL with glucose or
      glucose-6-phosphate produces AGE moieties on both the lipid and apolipoprotein B
      components. In addition, we tried to generate AGE-LDL by reaction with AGE
      peptides (< 10 kD) obtained by enzymatic digestion of long-term glycated
      fibronectin as a model for connective tissue AGE-peptides. AGE-formation can be
      assessed by monitoring of fluorescence (370/440 nm) which is easily
      differentiated from the much lower autofluorescence of oxidized low density
      lipoproteins (oxLDL). Alternatively, AGE formation was detected by an AGE
      specific ELISA using antibodies elicited in rabbits against bovine AGE-RNAse. In
      the present study we investigated the influence of oxidative stress on the long
      term glycation of LDL and the modulation of LDL-oxidation by AGE-modification. We
      observed (a) that the rate of AGE formation is reduced by BHT/EDTA both on LDL
      and serum albumin (glycation vs. glycoxidation), (b) long-term glycated LDL is
      more readily oxidized than unglycated LDL, (c) oxLDL is more prone to AGE
      modification, (d) AGE-modification of LDL strongly alters its epitope spectrum
      and (e) that aminoguanidine at higher concentrations (1-10 mM) inhibits copper
      catalyzed LDL oxidation in the way of a classical antioxidant.

PMID- 9259993
TI  - Quantitative determination of oLAb titers in various animal species.
AB  - It is generally accepted, that lipid peroxidation plays a pathogenic role in
      atherosclerosis. Furthermore, recent studies indicate that antibodies directed
      against oxidative modifications of Low Density Lipoprotein (oLAb) contribute to
      atherosclerotic processes and may have some function in other disorders. These
      antibodies have been determined predominantly in humans, because assays for oLAb
      measurement use species specific anti IgG conjugates. From such assay designs it
      is not possible to get directly comparable data from various animal species. Main
      advantages of comparable data between animal species are that results of animal
      experiments can be interpreted using human calibrators and that results of
      immunisations and production of monoclonal antibodies are directly comparable not
      only within, but also between animal species. The aim of this study was to find a
      modification for ELISAs for oLAb determination, which allows to measure sera of
      various animal species simultaneously. Microtitration plates were coated with
      oxidised LDL and blocked with bovine serum albumine. Human and animal sera were
      then pipetted into the plate in logarithmic serial dilutions and incubated for 2
      h at 37 degrees C. After washing, a protein A horse-radish peroxidase conjugate
      (Biomakor, Israel) was added to each well in a dilution of 1:20,000. The
      incubation conditions had to be optimized to achieve reliable results. After
      another washing step, the assay was developed with TMB. Absorptions were read at
      450 nm in a microplate photometer. Following the manufacturers incubation
      instructions, which recommended a duration of 1 h at room temperature, the system
      did not work optimally. No binding of protein A to IgG molecules bound to
      oxidised LDL could be observed, if the system was incubated at 37 degrees C. In
      our hands, best results were achieved for several animal species, if the
      conjugate was incubated for two hours at 2-4 degrees C in a refrigerator. Under
      these conditions, assay sensitivity was the same as in the standard method, which
      uses anti-species IgG conjugates. The protein A modification of oLAb allows
      direct reading of animal oLAb titres from human calibrators. With this method,
      results of animal experiments can be interpreted on the basis of the situation in
      humans. Preliminary results obtained show that immunisation experiments with
      oxidised LDL give serum titres in animals, which are in the same order of
      magnitude as human sera with high oLAb concentrations. The results of this study,
      in accordance with findings of other authors, give further indications that
      atherosclerotic processes are influenced by the specific immune system.

PMID- 9259994
TI  - Interactions between macrophages and oxidized low density lipoprotein in the
      presence of type I collagen.
AB  - In order to investigate the influence of collagen on the interactions between
      macrophages and oxidatively modified low density lipoprotein (ox-LDL), type I
      collagen was isolated from rat tail tendon and prepared as a gel. The binding of
      125I-ox-LDL, 125I-malondialdehyde (MDA)-LDL and 125I-acetyl-LDL to collagen was
      higher but the binding of 125I-4-hydroxynonenal (HNE)-LDL was lower than that of
      native 125I-LDL. When mouse peritoneal macrophages were cultivated on this
      collagen gel, most of the modified LDL was bound to the collagen gel rather than
      taken up by macrophages. The amount of modified 125I-LDL degraded by the
      macrophages decreased in the presence of the collagen gel. In the absence of gel
      a similar degree of reduction in degradation of modified 125I-LDL by macrophages
      was obtained when the cells were treated with cytochalasin D, an inhibitor of non
      specific phagocytosis. However, the treatment of the macrophages cultivated on
      the collagen gel with cytochalasin D did not influence the degradation of 125I-ox
      LDL and 125I-HNE-LDL. These results suggest that the uptake of ox-LDL by
      macrophages grown on collagen gel is primarily mediated via the scavenger
      receptors pathway, whereas in the absence of collagen also other mechanisms of
      uptake are operating.

PMID- 9259995
TI  - Lack of correlation between degree of human plasma low density lipoprotein
      oxidation and its atherogenic potential.
AB  - We have recently found that adducts of lipids, particularly cholesterol, with
      apolipoprotein B (apoB) are stable markers of human plasma low density
      lipoprotein (LDL) oxidation [7]. In this study we attempt to assess the
      relationship between the degree of plasma LDL oxidation, evaluated by the content
      of apoB-bound cholesterol and the ability of LDL to induce cholesterol
      accumulation in cultured human aortic intima smooth muscle cells, i.e., LDL
      atherogenic potential. LDL samples of 32 out of 39 healthy subjects did not
      increase cholesterol content in cells cultured from grossly normal intima of
      human aorta. Most of LDL preparations isolated from coronary atherosclerosis
      patients with (34 out of 43) or without (35 out of 45) hypercholesterolemia
      stimulated intracellular cholesterol accumulation by 32-302%. The ability of
      human LDL to induce cholesterol accumulation in aortic smooth muscle cells did
      not correlate with the degree of in vivo LDL oxidation (r = 0.10, n = 127). These
      results suggest that atherogenicity of LDL circulating in human plasma does not
      depend on the degree of lipid peroxidation in LDL particles.

PMID- 9259996
TI  - Pathways for oxidation of low density lipoprotein by myeloperoxidase: tyrosyl
      radical, reactive aldehydes, hypochlorous acid and molecular chlorine.
AB  - Many lines of evidence implicate oxidation of low density lipoprotein (LDL) in
      the pathogenesis of atherosclerosis, a chronic inflammatory disease. The
      physiologically relevant mechanisms have not been identified, but phagocytic
      white cells may play an important role because macrophage-rich lesions
      characterize the disorder. Recent studies have shown that myeloperoxidase, a heme
      enzyme secreted only by phagocytes, is present in human atherosclerotic tissue.
      The enzyme is a potent catalyst of LDL oxidation in vitro, it co-localizes with
      macrophages in lesions, and it generates products that are detectable in
      atherosclerotic plaque. These findings suggest that myeloperoxidase may promote
      LDL oxidation in the artery wall. This article reviews the enzyme's ability to
      generate a range of oxidants, including tyrosyl radical, reactive aldehydes,
      hypochlorous acid and molecular chlorine. These products have the potential to
      damage host molecules as well as microbes, suggesting a mechanism that may
      contribute to atherosclerotic vascular disease.

PMID- 9259997
TI  - Effects of plasma lipoproteins on the production of superoxide anion by human
      polymorphonuclear leukocytes in vitro.
AB  - Polymorphonuclear leukocytes (PMN) generate highly reactive oxygen derived free
      radicals that may cause lipoprotein lipid oxidation and so contribute to the
      pathogenesis of atherosclerosis. On the other hand it has been shown that
      lipoproteins can alter cell functions in vitro. We therefore studied the effects
      of atherogenic lipoproteins, VLDL and LDL, on the production of superoxide anion
      by human PMN in the presence or absence of formyl-methionyl-leucyl-phenylalanine
      (fMLP). VLDL and LDL stimulate PMN superoxide production and potentialize PMN
      stimulation by fMLP. The lipid moiety of the lipoproteins might be mainly
      involved in these effects. The binding of radio-labelled fMLP to its specific
      membrane receptor was significantly enhanced in the presence of VLDL and only
      slightly in the presence of LDL. The study of the signal transduction suggests
      that modulation of phospholipase D and A2 activities could be involved in the
      modification by LDL of PMN response to fMLP.

PMID- 9259998
TI  - Breakdown of oxidized proteins as a part of secondary antioxidant defenses in
      mammalian cells.
AB  - The degradation of oxidized proteins is an essential part of antioxidant defenses
      against free radical attack. Selective degradation of oxidatively damaged
      proteins allows proteolytic systems to function directly in the removal of
      useless cellular debris and therefore prevent the accumulation of potentially
      toxic fragments or large aggregates of cross-linked proteins. The degradation of
      oxidized proteins in dividing mammalian cells after hydrogen peroxide treatment
      has been demonstrated. Cells are able to increase proteolysis rates after
      treatment with moderate levels of oxidants. The role of proteasome in the removal
      of oxidized proteins has been demonstrated by treatment of cells with an anti
      sense oligodesoxynucleotide to the proteasome C2 subunit gene. This treatment
      decreases the proteasome content of the cells and prevents increased proteolysis
      rates after hydrogen peroxide treatment. Thus proteasome clearly plays a role in
      the removal of oxidized proteins. As part of antioxidant defenses the proteasome
      provides a second line of defense against the numerous radicals and oxidants
      which contact cells during their lifetime. The degradation of oxidatively damaged
      proteins enables-cells to recover from a moderate oxidant attack.

PMID- 9259999
TI  - Biogenic 4-hydroxy-2-nonenal activates transcription factor AP-1 but not NF-kappa
      B in cells of the macrophage lineage.
AB  - A large spectrum of pro-oxidant agents, including molecules with lipoperoxidative
      effect, can modulate gene expression through modification of the DNA binding
      activity of the transcription factors activator protein 1 (AP-1) and nuclear
      factor kappa B (NF-kappa B). In this study the effect on these redox-sensitive
      factors by 4-hydroxy-2-nonenal (HNE), a major aldehydic product of lipid
      peroxidation, was examined in two cell lines of the macrophage type. Incubation
      in the presence of microM concentrations of the aldehyde led to a rapid increase
      of AP-1 binding with a transient maximum 30 min from HNE addition to the culture
      medium in both cell lines. On the contrary, HNE did not stimulate nuclear
      translocation of NF-kappa B. The diverging effect of HNE on the two transcription
      factors is likely related to the demonstrated differential activation pathway of
      AP-1 and NF-kappa B in macrophages. The HNE-induced activation of AP-1 suggests
      the aldehyde's involvement in the regulatory mechanisms of cell proliferation and
      differentiation.

PMID- 9260001
TI  - The influence of oxidized lipoproteins, oxidation products and antioxidants on
      the release of nitric oxide from the endothelium and the response of platelets to
      nitric oxide.

PMID- 9260000
TI  - The mechanism of the hypochlorite-induced lipid peroxidation.
AB  - The article reviews data related to the role of exogenic hypochlorite (HOCl/OCl-)
      and hypochlorite produced by myeloperoxidase catalysis in initiation of lipid
      peroxidation (LPO) in phospholipid membranes and human blood lipoproteins (LP).
      It has been shown that HOCl/OCl- promotes free radical lipid oxidation in
      liposomes and LP that is followed by the formation of LPO products;
      hydroperoxides, conjugated dienes, TBARS, and fluorescent products. Water soluble
      reactive substances (.O2-, H2O2, Fe2+) which can be present in the reaction
      mixture as a dopant are not the source of free radicals and do not participate in
      HOCl/OCl(-)-induced LPO at the initiation step. The main reaction of HOCl/OCl-
      with unsaturated lipid is probably the generation of chlorohydrins. However, this
      reaction is not accompanied by generation of free radicals and LPO. HOCl/OCl-
      reacts efficiently with TBARS of aldehydic nature. It is likely that the reaction
      proceeds without the participation of free radicals. Among the compounds of a
      peroxide nature (hydro-, dialkyl-, diacyl-, alkyl-acyl-peroxide groups and
      epoxides) only hydroperoxides react with HOCl/OCl-. This reaction is accompanied
      by the production of free radicals (but not singlet oxygen), probably alkoxyl
      radicals, which may play a role in the initiation of HOCl/OCl(-)-induced LPO.

PMID- 9260002
TI  - Dynamics of oxidation of LDL and its inhibition by antioxidants.

PMID- 9260003
TI  - The effect of chronic treatment with NO donors during intimal thickening and
      fatty streak formation.
AB  - Intimal thickening in arteries is considered as a site of predilection for
      atherosclerosis. We investigated whether oral application of the nitric oxide
      (NO) donors SPM-5185 (N-nitratopivaloyl-S-(N'-acetylalanyl)-cysteine ethylester,
      10 mg/kg body weight/b.i.d.) and molsidomine (pro-drug of 3-morpholino
      sydnonimine (SIN-1), 10 mg/kg body weight/day) can retard intimal thickening and
      changes in vascular reactivity induced by a silicone collar positioned around the
      carotid artery of rabbits. Intimal thickening was significantly inhibited by SPM
      5185 (cross-sectional area 18 +/- 6 vs. 44 +/- 10 x 10(-3) mm2; P < 0.05), but
      not by molsidomine (28 +/- 6 vs. 35 +/- 9 x 10(-3) mm2), which is a donor of both
      NO and superoxide anions. In organ chamber studies collaring was associated with
      a decreased sensitivity to acetylcholine (ACh). SPM-5185 evoked a tendency
      towards normalization of the pD2 of ACh in collared arteries. We also
      investigated whether chronic nitric oxide (NO) treatment affected vascular
      reactivity and fatty streak development in the rabbit aorta. During 16 weeks
      rabbits received 150 g/day of a standard diet, or diets with 0.3% cholesterol,
      with 0.02% molsidomine (10 mg/kg body weight/day) or with the combination. The NO
      donor enhanced the area of fatty streaks, without affecting hypercholesterolemia.
      Moreover, it desensitized the smooth muscle cells of the rabbit aorta to
      vasodilators acting via the cytoplasmic guanylate cyclase and suppressed the
      capacity of the endothelial cells to release NO in response to muscarinic
      receptor stimulation. This suggested that chronic exposure to large quantities of
      NO caused a negative feedback, with selective decreases of both the endothelial
      capacity to generate NO and the responsiveness to vasodilators operating via
      cyclic GMP. In conclusion, we demonstrated that exogenous NO can decrease intimal
      hyperplasia in vivo. However, prolonged in vivo treatment with a donor of NO
      enhanced atherosclerosis in hypercholesterolemic rabbits.

PMID- 9260004
TI  - Use and misuse of syringes in anaesthesia.

PMID- 9260005
TI  - EMLA patch for intravenous cannulation in adult surgical outpatients.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of a single
      unit-dose package of the EMLA Patch for dermal analgesia during intravenous
      cannulation in adult, outpatients and in preventing vaso-vagal side effects.
      METHODS: After giving consent, 51 ASA I-III adult outpatients participated in a
      randomized, double-blind, placebo-controlled, parallel-group trial to receive
      either an EMLA or placebo patch applied to the intravenous cannula site for 60 to
      90 min. Following cannula insertion, patients and investigators rated the pain
      using a 100 mm VAS ruler. The incidence and severity of vaso-vagal responses,
      local skin reactions, and willingness to pay for the patch were also evaluated.
      RESULTS: The median VAS pain score by patient assessment in the EMLA patch group
      was lower (8 mm; range: 0-92) than in the placebo group (25 mm; range: 0-98, P <
      0.05). The median VAS pain score by investigator assessment was also lower in the
      EMLA patch group (15 mm; range 1-79) than in the placebo group (23 mm; range 3
      81, P < 0.05). There was a notable difference in the number of vaso-vagal
      reactions (17 placebo vs 4 EMLA, P < 0.05). Eighty-eight percent of patients who
      received the EMLA patch would be willing to pay for the patch in the future
      compared with 69% of the placebo patch patients. CONCLUSION: This study showed
      that the EMLA patch, applied for 60-90 min before venous cannulation reduced the
      pain of venepuncture and vaso-vagal side effects in adult outpatients.

PMID- 9260006
TI  - Peri-operative multimodal pain therapy for caesarean section: analgesia and
      fitness for discharge.
AB  - PURPOSE: To compare, the efficacy of a multi-modal analgesic regimen and single
      drug therapy with iv PCA morphine alter Caesarean delivery with spinal
      anaesthesia. METHODS: Forty ASA 1-2 parturients presenting for elective Caesarean
      section were randomized to receive multimodal pain treatment with intrathecal
      morphine, incisional bupivacaine and ibuprofen+acetaminophen po until hospital
      discharge (Group 1) or conventional therapy with iv PCA morphine weaned to
      acetaminophen+codeine po (Group 2). Both groups received spinal anaesthesia with
      1.7 ml hyperbaric bupivacaine 0.75%. Visual analog pain scores at rest (RVAPS)
      and with movement (DVAPS) were recorded q 2 hr during the first 24 hr, then q 4
      hr until discharge. Time to first walking, eating solid food, flatus, bowel
      movement, voiding and hospital discharge were recorded. RESULTS: Pain scores were
      lower in Group 1 patients during the first 24 hr after spinal injection RVAPS 0.6
      +/- 0.1 in Group 1 vs 2.1 +/- 0.1 in Group 2 (mean +/- SEM), DVAPS 1.9 +/- 0.1 in
      Group 1 vs 4.1 +/- 0.1 in Group 2 (P < 0.0001). Times to first flatus, 36.1 hr +/
      2.9 vs 20.5 +/- 1.8 (P < 0.05) and to first bowel movement, 74.8 hr +/- 5.6 vs
      57.4 +/- 4.7 (P < 0.0001) were longer in Group 2 patients. There was no
      difference between groups in time to eating solid food, walking or hospital
      discharge. CONCLUSION: Multi-modal pain therapy resulted in improved early post
      operative analgesia during the first 24 hr after Caesarean delivery. Patients
      receiving iv PCA morphine followed by acetaminophen+codeine po were more likely
      to develop decreased bowel mobility. All patients, with one exception, achieved
      discharge criteria (eating solid food, absence of nausea, normal lochia, dry
      incision and DVAPS < 4) at 48 hr after spinal injection.

PMID- 9260007
TI  - Comparison of tramadol and tramadol/droperidol mixture for patient-controlled
      analgesia.
AB  - PURPOSE: To compare the analgesic efficacy and side effects of tramadol vs
      tramadol and droperidol for post-operative patient-controlled analgesia (PCA).
      METHODS: Randomised, double-blind study. Thirty-four patients undergoing elective
      colorectal or head and neck surgery were allocated to Group 1 (n = 18, PCA bolus
      10 mg tramadol) or Group 2 (n = 16, PCA bolus 10 mg tramadol + 0.1 mg
      droperidol). Anaesthesia was induced with fentanyl and thiopentone and maintained
      with O2, N2O plus enflurane or isoflurane with iv morphine at doses decided by
      the attending anaesthetists. Muscle relaxation was achieved with atracurium or
      vecuronium. Patients were observed four-hourly for pain using an 11-point verbal
      rating scale (VRS). Nausea and vomiting, and sedation were assessed using four
      point scales post-operatively. Vital signs, request for rescue anti-emetic and
      analgesic, and overall satisfaction were recorded. RESULTS: The mean nausea
      scores were lower in Group 2 (1.00 +/- 1.33 vs 0.06 +/- 0.25 at 0-8 hr, 1.22 +/-
      1.93 vs 0.06 +/- 0.25 at 8-16 hr, P < 0.01; 0.81 +/- 1.68 vs 0 at 32-40 hr, P <
      0.05; Group 1 vs Group 2). The vomiting scores were also lower (0.50 +/- 1.04 vs
      0 at 0-8 hr, 0.67 +/- 1.50 vs 0, at 8-16 hr, P < 0.05; Group 1 vs Group 2). Seven
      (39%) patients in Group 1, but none in Group 2 requested rescue anti-emetic (P <
      0.01). There were no differences in VRS, sedation score, overall satisfaction or
      vital signs. CONCLUSION: Tramadol and droperidol combination is superior to
      tramadol alone for post-operative PCA. It provides a similar quality of analgesia
      with less nausea and vomiting and without an increase in sedation.

PMID- 9260008
TI  - Direction of injection does not affect the spread of spinal bupivacaine in
      parturients.
AB  - PURPOSE: One of the factors that can affect the distribution of local anaesthetic
      solutions in the subarachnoid space is the direction of the spinal needle through
      which injections are made. This study investigated the effect of the direction of
      the aperture of the Whitacre needle on the spread of hyperbaric bupivacaine in
      parturients undergoing elective caesarean section. METHODS: Forty healthy term
      parturients scheduled for caesarean delivery under spinal anaesthesia with 12 mg
      hyperbaric bupivacaine + 0.2 mg morphine were randomly assigned to one of two
      groups: needle orifice cephalad (I) or caudad (II). Spinal blocks were
      administered in the sitting position with patients being positioned supine
      immediately after. A blinded observer assessed the dermatome level of analgesia
      to ice every minute for the first 10 minutes, every three minutes for the
      following 35 min, then every 15 min until the sensory level regressed to T10.
      RESULTS: There was no difference between the groups regarding the maximal number
      of segments blocked cephalad to T11 (11.4 +/- 3.4: group I and 12.0 +/- 3.4:
      group II), time to highest cephalad spread of sensory block (22 +/- 10: group I
      and 19 +/- 10 min: group II), or time to regression to T10 (164 +/- 26: group I
      and 153 +/- 24 min: group II). The maximum decrease in blood pressure (33.9 +/-
      9.6: group I and 36.8 +/- 11.8 mmHg: group II) and dosage of ephedrine
      administered (14.7 +/- 10.7: group I and 16.2 +/- 11.0 mg: group II) did not
      differ. CONCLUSION: The direction of the aperture of the Whitacre needle does not
      influence the spread of hyperbaric bupivacaine in the term parturient.

PMID- 9260009
TI  - Prevention of PONV with granisetron, droperidol and metoclopramide in female
      patients with history of motion sickness.
AB  - PURPOSE: Motion sickness is one of the patient-related factors associated with
      postoperative nausea and vomiting (PONV). This study was undertaken to assess the
      efficacy of granisetron, droperidol and metoclopramide for preventing PONV in
      female patients with a history of motion sickness undergoing major gynaecological
      surgery. METHODS: In a prospective, randomized, placebo-controlled, double-blind
      study, 120 patients received either 1.25 mg droperidol, 10 mg metoclopramide, 40
      micrograms.kg-1 granisetron or placebo (saline) iv immediately before induction
      of anaesthesia. A standardized anaesthetic technique and postoperative analgesia
      were used in all patients. During the first 24 hr after anaesthesia, the
      incidence of PONV and adverse events were recorded by nursing-staff. RESULTS: The
      treatment groups were similar for patient demographics, types of surgery,
      anaesthetics administered and opioid given. The incidence of PONV was 70%, 50%,
      57% and 23% in the placebo, droperidol, metoclopramide and granisetron groups,
      respectively (P < 0.05; overall chi 2 test). No difference in the incidence of
      adverse events was observed in either group. CONCLUSION: Granisetron is a better
      prophylactic antiemetic than droperidol or metoclopramide in female patients with
      a history of motion sickness undergoing major gynaecological surgery.

PMID- 9260010
TI  - Low incidence of the oculocardiac reflex and postoperative nausea and vomiting in
      adults undergoing strabismus surgery.
AB  - PURPOSE: To investigate the incidence of the oculocardiac reflex (OCR), and of
      postoperative nausea and vomiting (PONV) in adults undergoing strabismus surgery.
      METHODS: Adults (18-86 yr) undergoing inpatient strabismus surgery received 10
      micrograms.kg-1 atropine and 10 micrograms.kg-1 altentanil iv and were randomly
      allocated to: (A) 5 mg.kg-1 thiopentone iv, isoflurane/N2O maintenance; (B) 3
      mg.kg-1 propofol iv, propofol/N2O maintenance (10-14 mg.kg-1.hr-1); 3 mg.kg-1
      propofol iv, propofol/air/O2 maintenance (10-14 mg.kg-1.hr-1). Analyses were with
      the number-needed-to-treat/harm. RESULTS: In 97 adults the absolute risk of OCR
      (13-20%) and PONV (21-31% after 24 hr) was low, with no differences between
      groups. Number-needed-to-treat to prevent PONV with propofol with or without N2O
      compared with thiopentone-isoflurane was 7 to 11. Number-needed-to-harm for one
      OCR with propofol compared with thiopentone-isoflurane was 17. CONCLUSION: Adults
      undergoing strabismus surgery with prophylactic atropine had a low risk of OCR
      and PONV, independent of the anaesthetic technique used.

PMID- 9260012
TI  - Postoperative elevation of creatine kinase (CK-MB): does it contribute to
      diagnosis of myocardial infarction?
AB  - PURPOSE: This retrospective study sought to determine the benefit of measurement
      of changes in plasma creatine kinase-myocardial band (CK-MB) levels in elective
      postoperative high risk surgical patients beyond that obtained from the surface
      12 lead ECG. METHODS: The charts of 111 patients admitted to the surgical
      intensive care unit (SICU) of a tertiary level university teaching hospital were
      reviewed. They were screened using predetermined definitions of myocardial
      infarction (MI) (as reflected by changes in the 12 lead surface ECG (Minnesota
      code) or elevations in CK-MB) for complications such as pulmonary oedema,
      congestive heart failure, arrhythmias, or cardiogenic shock. Four groups were
      identified based on changes in the ECG indicative of MI (Present-ECG+ or Absent
      ECG-) and elevations of CK-MB (Present-CKMB+ or Absent-CKMB-) and compared for
      the incidence of complications. RESULTS: No patient with ECG- findings had a
      complication. Fifteen patients with ECG+ findings were identified and all had
      complications. Fourteen of these patients had CKMB+ results. In contrast, 29
      patients with CKMB+ results alone (i.e., ECG-) had no complications. CONCLUSION:
      Clinically important (i.e., requiring therapeutic intervention) postoperative
      myocardial infarction was detected by ECG changes. The benefit of determining
      changes in CK-MB was minimal from a therapeutic perspective.

PMID- 9260011
TI  - Neostigmine requirements for reversal of neuromuscular blockade following an
      infusion of mivacurium.
AB  - PURPOSE: To study the efficacy of neostigmine compared with placebo for the
      antagonism of neuromuscular blockade at the end of a mivacurium infusion, and to
      determine its optimal dose. METHODS: One hundred adult patients undergoing an
      elective surgical procedure received a standardized anaesthetic with 20-30
      micrograms.kg-1 alfentanil, a propofol infusion and nitrous oxide. Muscle
      relaxation was maintained at 90-95% T1 depression with 0.2 mg.kg-1 mivacurium
      followed by an infusion. Neuromuscular blockade was measured with an integrated
      evoked electromyogram in response to train-of-four (TOF) stimuli at the ulnar
      nerve every 20 sec. Patients were randomized into four groups. At the end of
      surgery, the mivacurium infusion was stopped and patients received, immediately,
      in a double-blind manner, neostigmine (10, 20, or 40 micrograms.kg-1) or placebo
      according to a random number table. The T1 and TOF ratio were recorded until
      adequate recovery of neuromuscular function (TOF ratio > 0.70). During the
      reversal period, non-invasive blood pressure and heart rate were recorded every
      minute. The incidence of postoperative nausea and vomiting (PONV) was recorded in
      the recovery room. RESULTS: Data from 94 patients who completed the protocol were
      analysed. Compared with placebo, neostigmine 10 micrograms.kg-1 did not reduce
      the time to TOF > 0.70 (17.0 +/- 5.1 vs 14.6 +/- 4.2 min respectively). However
      the time was decreased with neostigmine 20 micrograms.kg-1 and 40 micrograms.kg-1
      (P < 0.001), but with no difference between these last two groups (11.4 +/- 3.0
      and 11.4 +/- 3.5 min respectively). Changes in systolic blood pressure and heart
      rate were not different between the four groups. Very few PONV events were
      observed in all groups (global incidence 7.4%). CONCLUSION: Recovery of
      neuromuscular blockade following a mivacurium infusion is accelerated by
      neostigmine. A dose of neostigmine 20 micrograms.kg-1 appears optimal with no
      further reduction in recovery time obtained from a larger dose.

PMID- 9260013
TI  - The role of the vasculature in regulating venous return and cardiac output:
      historical and graphical approach.
AB  - PURPOSE: To review the physiology of cardiac output regulation by the peripheral
      vasculature. This will enable the clinician to understand and manage the complex
      circulatory changes in various forms of shock, and in other common altered
      circulatory states encountered in anaesthetic practice. SOURCE: Articles were
      obtained from a Medline review (1966 to present; search terms: shock, venous
      return, cardiac output) and a hand search (Index Medicus). Other sources include
      review articles, personal files, and textbooks. PRINCIPAL FINDINGS: At steady
      state, cardiac output is equal to venous return (VR). Venous return depends on
      mean systemic pressure (PMS), which is the pressure in the peripheral vasculature
      driving blood flow to the heart, right atrial pressure (PRA), and the resistance
      to venous return (RV). When considering VR, PRA is the downstream pressure to VR,
      and not simply an indirect measure of the volume status. The pressure gradient
      for VR is, therefore, PMS-PRA, and in a system obeying Ohm's Law, [formula: see
      text] Shock and other altered circulatory states cause changes in both VR and
      cardiac function. The circulation can be conveniently described by a venous
      return and a cardiac output curve. By drawing these curves for each clinical
      situation, a clear understanding of the altered circulatory state is obtained,
      and treatment options can be clearly defined. CONCLUSION: The peripheral
      circulation controls cardiac output in many clinical conditions. Manipulation of
      the peripheral circulation is as important to the successful treatment of shock
      and other altered circulatory states, as is the manipulation of cardiac output.

PMID- 9260014
TI  - Extreme arterial blood pressure differentials in a patient with Takayasu's
      arteritis.
AB  - PURPOSE: To describe the extreme arterial blood pressure differentials in a
      patient with Takayasu's arteritis and its implications for the preservation of
      cerebral perfusion during anaesthesia. CLINICAL FEATURES: A 26-yr-old woman with
      Type III Takayasu's arteritis presented with a tentative diagnosis of mesenteric
      ischaemia. Determination of systolic arterial blood pressure assisted by oximetry
      revealed pressures of 114 mmHg in the left and 90 mmHg in the right arm while
      direct arterial line pressure monitoring of the left posterior tibial artery
      showed a pressure of 322/113 mmHg. Following induction of anaesthesia with
      thiopentone and succinylcholine and maintenance with N2O, isoflurane and
      fentanyl, posterior tibial arterial pressures were maintained (low of 213/96
      mmHg) to maintain cerebral blood flow despite surgical requests to lower blood
      pressure. Epidural local anaesthesia was not considered for intra- or
      postoperative management due to the regional differences in blood pressure and
      the effect that sympatholysis may have had on cerebral perfusion. CONCLUSION: In
      patients with Takayasu's arteritis, extreme arterial blood pressure differentials
      may exist which may affect regional blood flow, and monitoring of both upper and
      lower extremity arterial blood pressure should be considered.

PMID- 9260015
TI  - Anterior cervical myelopathy in the early postoperative period.
AB  - PURPOSE: The onset of anterior cervical myelopathy in the early postoperative
      period is an unusual complication after cardiac surgery without extracorporeal
      circulation in which haemodynamic stability was maintained. We report a patient
      who developed anterior cervical myelopathy after cardiac surgery. CLINICAL
      FEATURES: A 53-yr-old man with no serious associated medical problems underwent
      cardiac surgery without extracorporeal circulation to repair a ruptured left
      ventricle. Haemodynamic stability was maintained throughout the procedure but the
      patient developed flaccid paraparesis and dissociated sensory loss, three hours
      later. Early recognition of the clinical picture and prompt initiation of steroid
      treatment facilitated a successful outcome. The definitive diagnosis was based on
      magnetic resonance findings days after surgery. CONCLUSION: The onset or
      aggravation of neurological symptoms in the postoperative period may be avoided
      by thorough search for medullary pathology in the patient's background and by
      using particular care when performing manoeuvres during the perioperative period,
      not only to ensure haemodynamic stability, thus preserving medullary perfusion,
      but also to avoid mechanical compression of a spinal segment.

PMID- 9260016
TI  - Light-guided retrograde intubation.
AB  - PURPOSE: Transillumination of the soft tissues using a lightwand (Trachlight) can
      guide the endotracheal tube (ETT) into the glottis to facilitate the retrograde
      intubation. This study evaluated the effectiveness and safety of this intubating
      technique for patients with cervical spine instability. METHODS: After obtaining
      institutional approval and informed consent, 27 patients were studied. Light
      guided retrograde intubation was performed either awake, or under general
      anaesthesia. Following cricothyroid membrane puncture using a # 18 i.v. catheter,
      an epidural catheter was advanced cephalad into the oropharynx. While pulling the
      epidural catheter taut, the ETT, with the Trachlight in place, was advanced into
      the glottis. When the tip of the ETT entered the glottis, a bright glow was seen
      in the anterior neck. The number of attempts, failures, complications, the times
      required to puncture the cricothyroid membrane, insert the epidural catheter, and
      insert the ETT into the trachea were recorded. RESULTS: In all patients, the
      tracheas were successfully intubated. The mean (+/-sd) time to perform
      cricothyroid puncture, insert the epidural catheter, and place the ETT into the
      trachea were 66.1 +/- 56.2, 74.0 +/- 25.2, and 72.8 +/- 42.5 sec respectively.
      The average total-time for this light-guided retrograde intubating technique was
      205.8 +/- 78.3 sec. Apart from minor bleeding at the cricothyroid membrane
      puncture site, there were no major complications. CONCLUSION: In a small number
      of patients, we have shown that light-guided retrograde intubation is effective
      and sale for patients with cervical spine instability. This simple and
      inexpensive technique may prove to be a valuable adjunct in the management of
      difficult airways.

PMID- 9260017
TI  - Magnesium deficiency increases ketamine sensitivity in rats.
AB  - PURPOSE: Inhibition of the NMDA receptor likely contributes to ketamine's
      neurodepressive properties. Magnesium also inhibits the NMDA receptor by binding
      to a site associated with the ketamine-binding domain. Electrophysiological
      studies suggest that magnesium prevents ketamine from binding to the NMDA
      receptor and thereby prevents ketamine inhibition. We undertook an in vivo study
      to determine if magnesium deficiency was associated with an increased sensitivity
      to ketamine. METHODS: Weanling rats were maintained on a Mg(2+)-deficient or
      control diet for 14 days. In Study I, rats were anaesthetized then sacrificed and
      the Mg2+ concentrations in the brain and plasma were measured. In a second
      prospective study, experimental animals were rendered hypomagnesaemic and the
      potency of 125 mg.kg-1 ip ketamine was evaluated. Animals were then were fed a
      Mg(2+)-containing diet and ketamine sensitivity was re-examined 14 days later.
      RESULTS: The Mg(2+)-deficient diets rendered the rats hypomagnesaemic as
      indicated by the brain and plasma concentration of Mg2+. In Study 2, the time to
      loss of righting reflex was shorter; 1.9 +/- 0.3 min (n = 12) and 2.6 +/- 0.2 min
      (n = 16, P < 0.05), whereas the latency to toe pinch was prolonged: 25.0 +/- 5.8
      min (n = 12) vs 3.1 +/- 2.1 min (n = 16, P < 0.05) in the Mg(2+)-deficient
      compared with age-matched control animals, respectively. The hypomagnesaemic
      animals had a higher death rate following ketamine injection. The increased
      sensitivity to ketamine was no longer apparent when the animals were re-tested
      following replenishment of Mg2+. CONCLUSION: Hypomagnesaemia is associated with
      an increased sensitivity to ketamine.

PMID- 9260018
TI  - Residual neuromuscular blockade after cardiac surgery: pancuronium vs rocuronium.
AB  - PURPOSE: To determine the incidence of residual neuromuscular blockade after
      cardiac surgery in patients receiving either rocuronium or pancuronium for muscle
      relaxation. METHODS: In a prospective, controlled, double-blind study, 20
      patients undergoing coronary artery bypass were randomized to receive either
      rocuronium (n = 10) or pancuronium (n = 10) during surgery. Anaesthesia was
      induced with sufentanil, benzodiazepine and propofol or ketamine, and maintained
      with air/O2/sufentanil/isoflurane. Neuromuscular blockade was induced with 0.1
      ml.kg-1 from blinded syringes containing recuronium (6 mg.ml-1) (Group R) or
      pancuronium (1 mg.ml-1) (Group P). Relaxants were administered according to
      clinical criteria and reversal agents were not given. After surgery,
      neuromuscular transmission was assessed by train-of-four stimulation of the ulnar
      nerve/adductor pollicis EMG (Datex Relaxograph). Mean values from three trains of
      stimuli were recorded and repeated 30 min later if TOF ratio was < 0.7. Time to
      extubation was recorded. RESULTS: On arrival in the ICU, nine of 10 patients in
      group R but only three of 10 patients in group P demonstrated four visible
      responses (P < 0.05). Mean TOF ratio in group P, 0.03 +/- 0.05, was less than in
      group R, 0.68 +/- 0.34 (P < 0.001). All patients in group P and 4 of 10 patients
      in group R had TOF ratio < 0.7 (P = 0.01). Time to extubation in group P (median
      18, range 6-48 hr) was not statistically different from that in group R (14, 5-44
      hr). CONCLUSION: Residual neuromuscular block, TOF ratio < 0.7, is common after
      cardiac surgery but the incidence is less when pancuronium is replaced by
      rocuronium.

PMID- 9260019
TI  - An emergency pocket drug case of the 1940s.
AB  - PURPOSE: A description is given of an emergency box dating from about 1940. Its
      compact and portable nature, and certain of its contents, while throwing light on
      the working conditions of the times, raised a question as to its purpose and
      provenance. PRINCIPLE FEATURES: The main contents-the box and its contents are
      described, and the possible use of its constituents is considered. The drugs fall
      into five main groups: anaesthetic premedicants, medullary stimulants,
      vasoconstrictors, cardiac stimulants and drugs acting on the uterus. It is
      suggested that their primary purpose was for emergency obstetric use. CONCLUSION:
      It is concluded that the most probable purpose was for use by the obstetric
      'Flying squad.' A brief account of the constitution of such a squad, and its
      method of working, is given.

PMID- 9260020
TI  - Intubating conditions and correct application of cricoid pressure during rapid
      sequence induction: who should hold the mask?

PMID- 9260021
TI  - Pharmacological properties of the denervated heart.

PMID- 9260022
TI  - Bolus size and PCA morphine requirements.

PMID- 9260033
TI  - Clinical pharmacokinetics and pharmacodynamics of selegiline. An update.
AB  - Selegiline is a selective inhibitor of monoamine oxidase-B (MAO-B) at a dose of
      10 mg/day and is given to patients with Parkinson's disease as an adjunct to
      levodopa therapy. By inhibiting MAO-B, selegiline increases the dopamine levels
      in the substantia nigra. Selegiline also blocks dopamine re-uptake from the
      synaptic cleft, thus increasing the dopamine concentrations in the brain. At a
      dose of 10 mg/day, selegiline is devoid of 'cheese effect'. The pharmacokinetics
      of selegiline are highly variable. Following an oral dose of selegiline 10 mg, it
      is rapidly absorbed and metabolised to desmethylselegiline, levoamphetamine and
      levomethamphetamine. The mean peak plasma concentration (Cmax) is approximately 2
      micrograms/L and the time to reach the peak is under an hour. The absolute
      bioavailability of selegiline is approximately 10%. It has an apparent volume of
      distribution of 1854 L. The oral clearance of selegiline (59 L/min) is many fold
      higher than the liver blood flow (1.5 L/min), indicating that extrahepatic
      processes are involved in the elimination of selegiline. The elimination half
      life of selegiline is about 1.5 hours. Following multiple administration of
      selegiline 10 mg/day, the accumulation of both the parent compound and its
      metabolites have been reported. At least a 4-fold increase in the half-lives of
      selegiline and desmethylselegiline has been reported. There is at least a 3-fold
      increase in the Cmax and area under the concentration-time curve of selegiline
      with food. One of the metabolites of selegiline, desmethylselegiline, is believed
      to posses some MAO-B inhibitory property, though to a lesser extent than that of
      selegiline. Within 2 to 4 hours of an oral dose of selegiline 10 mg, 86% of the
      platelet MAO-B activity was inhibited and it took almost 2 weeks for platelet MAO
      B activity to return to the baseline values. Transdermal administration of
      selegiline resulted in an increase in the plasma concentrations of selegiline and
      a decrease in the formation of its metabolites, indicating that the extensive
      first-pass effect is avoided when selegiline is given transdermally.

PMID- 9260036
TI  - An evaluation of the integration of pharmacokinetic and pharmacodynamic
      principles in clinical drug development. Experience within Hoffmann La Roche.
AB  - The integration of pharmacokinetic and pharmacodynamic principles into drug
      development has been proposed as a way of making it more rational and efficient.
      The use of these principles in drug development to make scientific and strategic
      decisions is defined as the 'pharmacokinetic-pharmacodynamic guided approach to
      drug development'. The objectives of this survey were: (i) to assess the extent
      the pharmacokinetic-pharmacodynamic guided approach to drug development has been
      used in a large multinational pharmaceutical company: (ii) to evaluate the impact
      of pharmacokinetic and/or pharmacodynamic results on clinical drug development;
      and (iii) to identify factors which prevented the full application of the
      pharmacokinetic-pharmacodynamic guided approach. This was done by looking at 18
      projects in the current development portfolio at Hoffman La Roche and evaluating
      the use of this approach by interviewing the responsible clinical pharmacologist
      using a standardised questionnaire. (i) Benefits from using the pharmacokinetic
      pharmacodynamic guided approach were reported in every project, independent of
      development phase and therapeutic area. This approach was more extensively used
      in the recent projects. The selection of dosages in clinical studies was found to
      be the most important application of pharmacokinetic-pharmacodynamic results in
      terms of an impact on drug development. (ii) Time savings, up to several months,
      could be quantified in 8 projects during the entry-into-man studies and in 6
      projects during the phase II or III studies. In 4 projects, 1 clinical study was
      avoided. (iii) The most important scientific factor preventing the full
      application of the approach was the lack of knowledge on the predictive value of
      the pharmacodynamic or surrogate marker for effect (6 projects). The results of
      the survey have shown that the use of the pharmacokinetic-pharmacodynamic guided
      approach has contributed to making clinical drug development more rational and
      more efficient. Opportunities to apply the pharmacokinetic-pharmacodynamic
      approach should be identified in each project and a project specific strategy for
      the pharmacokinetic-pharmacodynamic guided approach should be defined during
      phase 0 of drug development.

PMID- 9260032
TI  - Pharmacokinetic interactions between alcohol and other drugs.
AB  - The frequent use of alcohol (ethanol) together with prescription drugs gives any
      described pharmacokinetic interaction significant clinical implications. The
      issue is both the effect of alcohol on the pharmacokinetics of various drugs and
      also the effect of those drugs on the pharmacokinetics of alcohol. This review
      discusses these pharmacokinetic interactions but also briefly describes some
      other effects of alcohol that are clinically relevant to drug prescribing. The
      use of several different study designs may be required before we can confidently
      state the presence or absence of any alcohol-drug interaction. Short term
      administration of alcohol in volunteers is the most common study design but
      studies of social drinking and prolonged moderate alcohol intake can be important
      in some situations. Community-based studies may illustrate the clinical relevance
      of any interaction. Alcohol can affect the pharmacokinetics of drugs by altering
      gastric emptying or liver metabolism (by inducing cytochrome P450 2E1). Drugs may
      affect the pharmacokinetics of alcohol by altering gastric emptying and
      inhibiting gastric alcohol dehydrogenase. The role of gastric alcohol
      dehydrogenase in the first-pass metabolism of alcohol is reviewed in this article
      and the arguments for and against any potential interaction between alcohol and
      H2 receptor antagonists are also discussed. The inhibition of the metabolism of
      acetaldehyde may cause disulfiram-like reactions. Pharmacodynamic interactions
      between alcohol and prescription drugs are common, particularly the additive
      sedative effects with benzodiazepines and also with some of the antihistamine
      drugs; other interactions may occur with tricyclic antidepressants. Alcohol
      intake may be a contributing factor to the disease state which is being treated
      and may complicate treatment because of various pathophysiological effects (e.g.
      impairment of gluconeogenesis and the risk of hypoglycaemia with oral
      hypoglycaemic agents). The combination of nonsteroidal anti-inflammatory drugs
      and alcohol intake increases the risk of gastrointestinal haemorrhage.

PMID- 9260037
TI  - Smoking and attention: a review and reformulation of the stimulus-filter
      hypothesis.
AB  - An accumulation of evidence suggests that smoking may be reinforcing, in part,
      due to nicotine's capacity to enhance attentional processing. Correspondingly,
      the stimulus-filter model of nicotine reinforcement asserts that nicotine
      facilitates cognitive performance by acting as a stimulus-barrier, thereby
      screening irrelevant and annoying stimuli from the smoker's awareness. A review
      of the available data suggests that while nicotine does appear to reliably
      enhance sustained, divided, and focused attention, the stimulus-filter model
      falls short of adequately explaining the findings. An alternative, attention,
      allocation model of nicotine reinforcement is reviewed, the tenets of which
      suggest that nicotine differentially augments attentional processing via its
      propensity to: (a) induce attentional narrowing, and (b) increase perceptual
      processing capacity. The motivational implications of the model, including
      smokers' use of nicotine to dampen stress, are discussed.

PMID- 9260034
TI  - Drug interactions with grapefruit juice.
AB  - Some drugs demonstrate a significantly greater (up to 3-fold) mean oral
      bioavailability on coadministration with grapefruit juice. With some calcium
      antagonists, the benzodiazepines midazolam and triazolam and the antihistamine
      terfenadine, changes in bioavailability are accompanied by altered drug action.
      Study design factors possibly contribute to the magnitude of changes in drug
      bioavailability; they include the source of the citrus, its intake schedule, drug
      formulations and individual metabolising capacity. The components of citrus juice
      that are responsible for clinical drug interactions have yet to be fully
      determined. Based on the flavonoid naringin's unique distribution in the plant
      kingdom, abundance in grapefruit and ability to inhibit metabolic enzymes,
      naringin is likely to be one of the grapefruit components influencing drug
      metabolism. Other components present in citrus fruit, such as furanocoumarins,
      may be more potent inhibitors than flavonoids and are under investigation.
      Conclusions drawn from clinical drug interaction studies should be considered
      specific to the citrus fruit products evaluated because of the variation in their
      natural product content. The predominant mechanism for enhanced bioavailability
      is presumably the inhibition of oxidative drug metabolism in the small intestine.
      The consistent findings across studies of diverse cytochrome P450 (CYP) 3A
      substrates support the mechanistic hypothesis that 1 or more grapefruit juice
      components inhibit CYP3A enzymes in the gastrointestinal tract. The evaluation of
      the need to avoid the concomitant intake of grapefruit products with drugs is
      best done on an individual drug basis rather than collectively by drug class.
      Based on the narrow therapeutic range of cyclosporin and research experience in
      organ transplant recipients, its interaction with grapefruit juice is likely to
      be clinically significant.

PMID- 9260035
TI  - Bioequivalence of chiral drugs. Stereospecific versus non-stereospecific methods.
AB  - Guidelines for bioequivalence of non-racemic pharmaceuticals are abundant in the
      literature. However, few guidelines exist for the bioequivalence of racemic drugs
      which consist of 2 or more stereoisomers. The aim of this article is to address
      the question of whether the bioequivalence of racemic drugs should be based on
      the measurement of the individual enantiomers or that of the total drug. Several
      pharmacokinetic-pharmacodynamic cases are examined to test the validity of
      extrapolating the bioequivalence of racemic drugs to that of their individual
      enantiomers after administration of the racemate; simulation and experimental
      data are presented to support these cases. It is shown that for drugs which
      exhibit non-linear pharmacokinetics, the results of bioequivalence studies based
      on the total drug may differ from those based on the individual enantiomers.
      Similar discrepancies can be shown for a racemic drug with linear
      pharmacokinetics whose enantiomers substantially differ from each other in their
      pharmacokinetic parameters. Therefore, it is suggested that stereospecific assays
      be used for these drugs. Additionally, it is recommended that for racemic drugs
      which undergo chiral inversion, and for most products with modified release
      characteristics, the bioequivalence be assessed using stereospecific assays.
      Conversely, for racemic drugs with linear pharmacokinetics and minimal to modest
      stereoselectivity in their kinetic parameters, and for those with non
      stereoselective pharmacodynamics, the use of stereospecific analytical methods
      are not warranted. Finally, the limited, controversial literature in favour of or
      against the use of stereospecific assays in bioequivalence of chiral drugs are
      reviewed and a preliminary guideline is proposed.

PMID- 9260038
TI  - Cognitive distortions in sex offenders: an integrative review.
AB  - Clinicians and researchers have noted that maladaptive beliefs and distorted
      thinking play an important role in facilitating or justifying sexual offenses.
      There have been a number of attempts to describe the nature of these beliefs and
      to develop ways of measuring them, but in the absence of any integrating theory.
      We suggest that an understanding of the cognitive processes underlying the
      initiation, maintenance, and justification of sexual offending is a vital
      prerequisite to the development of successful treatment programs. In this paper,
      we use a social cognition framework to review the literature on the role of
      cognition in sexual offending. Pertinent research in the sexual offending domain,
      specifically cognitive products, information processing, cognitive change, and
      the impact of affective and motivational factors on cognitive processes, is
      described and related to the social cognitive approach. Implications for future
      research and clinical practice are discussed in light of the major issues and
      problems highlighted in our review.

PMID- 9260039
TI  - Traumatic intrusive imagery as an emotional memory phenomenon: a review of
      research and explanatory information processing theories.
AB  - Intrusive imagery is both a common response to trauma and a hallmark of
      Posttraumatic Stress Disorder. However, its features and underlying mechanisms
      have not been reviewed systematically. This paper delineates the characteristics
      of intrusions and critically reviews the literature, conceptualizing intrusive
      imagery as an emotional memory phenomenon. This approach integrates otherwise
      separate research arenas in emotion and memory, psychobiology, pharmacology, and
      physiology, which converge to suggest that intrusive imagery is driven primarily
      by affective arousal and sympathetic nervous system reactivity. These basic and
      applied research findings are addressed directly by three information processing
      theories, which are reviewed and critiqued for their heuristic value in
      accounting for intrusions. Directions for research, treatment, and assessment are
      presented.

PMID- 9260041
TI  - Trichotillomania: a comprehensive behavioral model.
AB  - As our knowledge of chronic hair pulling as neither rare nor benign has
      increased, so has the need for a comprehensive framework to guide our
      conceptualization of this disorder for both research and clinical work. Such a
      model is presented which incorporates (a) the varied antecedents that both cue
      the impulse to pull and facilitate pulling, (b) the wide array of behaviors
      involved in the actual pulling, and (c) the full range of consequences of
      pulling. The cyclical nature of pulling episodes is highlighted.

PMID- 9260040
TI  - Psychotherapy for female sexual dysfunction: a review.
AB  - The increasing recognition of the significant incidence of female sexual
      dysfunction as well as the increasing acceptance of sex therapy as the preferred
      option for addressing problems in sexual functioning give rise to questions as to
      effectiveness of psychotherapy for female sexual dysfunction. This article
      presents a review of empirical studies of the treatment of female sexual
      dysfunction that meet minimal methodological criteria. Because of the variety and
      seriousness of methodological problems in the studies reviewed, guidelines for
      sample selection and description, research design, assessment and classification,
      and data analysis are provided. In addition, the 21 studies reviewed are examined
      for information they give about the treatment of female sexual dysfunction.

PMID- 9260042
TI  - Regulation of salivary-gland-specific gene expression.
AB  - The results from in vivo transgenic and in vitro transfection studies designed to
      identify cis-element(s) and transfactor(s) governing the salivary proline-rich
      proteins (PRPs), amylase, and parotid secretory protein (PSP) gene expression are
      utilized as a paradigm to discuss the regulation of salivary-specific gene
      expression. Particular attention is given to the molecular mechanism(s)
      underlying the salivary PRP R15 gene regulation. In rodents, the PRPs are
      selectively expressed in the acinar cells of salivary glands, and are inducible
      by the beta-agonist isoproterenol and by dietary tannins. The results from a
      series of experiments using chimeric reporter constructs containing different
      lengths of the R15 distal enhancer region, their mutations, and various
      expressing constructs are analyzed and discussed. These data suggest that the
      inducible nuclear orphan receptor NGFI-B may participate in the regulation of
      salivary acinar-cell-specific and inducible expression of the rat R15 gene via
      three distinct distal NGFI-B sites. Taken together, a model for the induction of
      R15 gene expression by Ipr is proposed. However, the exact molecular basis of
      this NGFI-B-mediated transactivation of cAMP-regulated R15 expression remains to
      be established.

PMID- 9260043
TI  - Is fibroblast heterogeneity relevant to the health, diseases, and treatments of
      periodontal tissues?
AB  - There are wide variations of gene expression and strikingly different responses
      to extracellular signals among different fibroblast populations. This has
      prompted a large number of in vitro studies which suggest that fibroblasts are
      not homogeneous but instead comprise multiple subpopulations with extensive site
      to-site and intra-site variations. Conceivably, either fibroblasts are not all
      created equal, or, alternatively, discrete subpopulations may emerge in
      development, inflammatory lesions, or wound healing. While the heterogeneous
      nature of cultured fibroblasts has been known for some time, are these variations
      relevant to our understanding of the biology of oral tissues, their involvement
      in disease, and their response to therapy? Since fibroblasts are the predominant
      cell type in soft connective tissue matrices, the regulation of their
      proliferative, synthetic, and degradative behavior is likely to be important in
      tissue physiology and pathology. In this review, we use the current literature to
      assess whether fibroblast subpopulations really make a difference in the health
      and disease of periodontal tissues. We address the following questions: (1) Is
      fibroblast heterogeneity a real in vivo phenomenon? (2) How can we advance our
      knowledge of phenotypic variations and the regulation of fibroblast
      differentiation? (3) Could a knowledge of fibroblast heterogeneity have an impact
      on the development of new approaches to pathogenesis and the treatment of
      periodontal tissues?

PMID- 9260045
TI  - Epidemiology of temporomandibular disorders: implications for the investigation
      of etiologic factors.
AB  - Epidemiology is the study of the distribution, determinants, and natural history
      of disease in populations. Epidemiology has several uses in addition to its
      traditional role of documenting the public health significance of a condition.
      Notably, epidemiologic methods and data can be used to identify and verify causes
      of disease. This article reviews the epidemiologic data on pain in the
      temporomandibular region, and on signs and symptoms associated with specific
      subtypes of temporomandibular disorders, with the aim of identifying possible
      etiologic factors for these conditions that deserve further study. Despite
      methodologic and population differences, several consistencies are apparent in
      the epidemiologic literature. Pain in the temporomandibular region appears to be
      relatively common, occurring in approximately 10% of the population over age 18;
      it is primarily a condition of young and middle-aged adults, rather than of
      children or the elderly, and is approximately twice as common in women as in men.
      This prevalence pattern suggests that etiologic investigations should be directed
      at biologic and psychosocial factors that are more common in women than in men,
      and diminish in older age groups. Most signs and symptoms associated with
      particular temporomandibular disorders (e.g., joint sounds, pain in the joint)
      also appear to be more prevalent in women than in men, although age patterns for
      these signs and symptoms are not as clear as for temporomandibular pain. The
      available data highlight the need for further research on etiologic factors
      associated with temporomandibular pain and with specific diagnostic subtypes of
      temporomandibular disorders.

PMID- 9260044
TI  - Short-chain carboxylic-acid-stimulated, PMN-mediated gingival inflammation.
AB  - This communication reviews the effects of short-chain carboxylic acids on human
      cells of importance to the periodontium. The central hypothesis is that these
      acids can alter both cell function and gene expression, and thus contribute to
      the initiation and prolongation of gingival inflammation. Short-chain carboxylic
      acids [CH3-(CH2)x-COOH, x < 3] are metabolic intermediates with a broad range of
      apparently paradoxical biological effects. For example, lactic acid (CH3-CHOH
      COOH), a 3-carbon alpha-hydroxy-substituted acid, is widely recognized for its
      cariogenicity. Lactic acid, however, also occurs in tropical fruits, and is the
      active ingredient in a variety of anti-wrinkle creams developed by
      dermatologists. In marked contrast, the unsubstituted 3-carbon propionic acid
      (CH3-CH2-COOH) is used as a food preservative and is the active principle for one
      class of non-steroidal anti-inflammatory agents. Interestingly, the addition of
      one carbon to propionic acid dramatically changes the biological effects. The
      unsubstituted 4-carbon butyric acid (CH3-CH2-CH2-COOH) is used by hematologists
      as a de-differentiating agent for the treatment of sickle cell anemia, but by
      oncologists as a differentiating agent for cancer chemotherapy. Finally, acting
      either individually or in concert, these acids can increase vascular dilation.
      Clearly, these acids, while metabolically derived, have a number of very
      divergent activities which are cell-type-specific (Fig. 1). It may be telling
      that periodontal bacteria produce these acids in millimolar concentrations, and
      that these bacteria can be characterized by their acid production profiles. It is
      no less interesting that these acids occur in the gingival crevices of human
      subjects with severe periodontal disease at millimolar levels which are > 10-fold
      higher than those found in mildly diseased subjects, and are undetectable in
      healthy subjects. Further, when applied directly to healthy human gingiva, short
      chain carboxylic acids stimulate a gingival inflammatory response and
      inflammatory cytokine release. At the cellular level, these acids inhibit
      proliferation of gingival epithelial and endothelial cells, and inhibit leukocyte
      apoptosis and function, but can stimulate leukocyte cytokine release. At the
      molecular level, these acids can stimulate neutrophil gene transcription,
      translation, and protein expression. Thus, the likelihood is high that these
      acids, in addition to their cariogenic activity, can promote and prolong gingival
      inflammation. Our challenge will be to identify the cell or cells of the
      periodontium which respond to short-chain carboxylic acids, to delineate their
      responses and the molecular mechanism(s) of these effects, and to categorize the
      aspects of the inflammatory components which damage and those which protect the
      host. With this information, it may be possible to begin to rationally identify
      and test pharmaceutical agents which diminish the harmful aspects, while
      enhancing the beneficial components, of the inflammatory response.

PMID- 9260046
TI  - Current concepts on adhesion to dentin.
AB  - This review examines fundamental concepts in bonding to dentin. Emphasis is
      placed on the structure and permeability characteristics of dentin and how they
      may influence its interaction with adhesive resin. Several new techniques to
      examine the interfaces between resin and dentin are reviewed along with some of
      their limitations. The advantages and disadvantages of acid etchants/conditioners
      vs. self-etching conditioners/primers are discussed. The problems of matching the
      surface tension of resin-bonding systems to the surface energy of the substrate
      are reviewed in terms of wetting the various components of dentin. The problems
      associated with matching the permeability of intertubular dentin to the
      diffusibility of bonding reagents are explored. Speculation is advanced on how to
      ensure polymerization and wetting of dentinal collagen. Theoretical problems
      associated with dentin bonding and with bond testing are reviewed to encourage
      future research in this rapidly developing area.

PMID- 9260047
TI  - Periodontal probing.
AB  - For decades, probing clinical pocket depth and attachment level have been
      recognized as the dentist's most important tools in diagnosing periodontal health
      and disease. They are physical methods to measure the distance from the bottom of
      a pocket to a reference line, usually the gingival margin or the cemento-enamel
      junction. Probing accuracy and precision are affected by factors like the design
      of the probe, probing force, probe position, pocket depth, or tissue
      inflammation. Recently, several new electronic periodontal probes have been
      developed. They feature high instrument precision, allowing for measurements to
      the nearest tenth of a millimeter. They control for probing force and permit data
      to be collected and stored electronically. The purpose of this review paper is to
      summarize various aspects of periodontal probing. First, the history of
      periodontal probes will be briefly recollected, and interesting and significant
      inventions of the past and the present emphasized. Then, the importance of the
      periodontal tissues relative to probe tip penetration will be reviewed, and the
      probing performance will be discussed. The paper will conclude with notes on
      selected statistical issues.

PMID- 9260048
TI  - Hematologic malignancies.

PMID- 9260049
TI  - Epidemiology of childhood leukemia.
AB  - Leukemia is the most common malignancy among children under the age of 15. It has
      recently been shown that the incidence rate of acute lymphoblastic leukemia, the
      predominant type of childhood leukemia in the United States and many European
      countries, is increasing among young children. Several recent etiologic studies
      focusing on the investigation of leukemia risk among young children have
      suggested that maternal exposures during pregnancy, such as low-dose radiation
      from the Chernobyl accident, parental alcohol consumption, and dietary habits,
      may be related to the risk of leukemia in infants. Paternal preconception smoking
      has also been reported to be associated with an increased risk of childhood
      leukemia, particularly among young children. Other etiologic hypotheses
      investigated recently include the association of childhood leukemia with
      infection and with birth weight. This paper briefly surveys the progress of
      epidemiologic research on childhood leukemia in 1996.

PMID- 9260050
TI  - Recent advances in the biology and treatment of childhood acute lymphoblastic
      leukemia.
AB  - The molecular analysis of genetic alterations in acute lymphoblastic leukemia has
      led to the development of molecular diagnostic techniques that have improved the
      biologic characterization of newly diagnosed patients. Modern treatment protocols
      rely on this information to tailor the intensity of therapy to the risk of
      relapse. For example, the TEL-AML1 fusion, the most common genetic abnormality in
      childhood acute lymphoblastic leukemia, was recently shown to be an independent,
      favorable prognostic factor, suggesting that patients with this abnormality are
      best treated with conventional antimetabolite-based therapy. Extremely high-risk
      patients, such as those with MLL gene rearrangements, are now considered
      candidates for alternative treatments, such as allogeneic bone marrow
      transplantation in first remission. Efforts are currently being made to reduce
      the long-term sequelae of therapy and to use molecular techniques to monitor
      minimal residual disease.

PMID- 9260051
TI  - Advances in the detection of minimal residual disease.
AB  - The study of minimal residual disease (MRD) is an attempt to detect and define
      the significance of leukemia invisible to normal morphologic examination. In many
      circumstances the clinical significance of MRD detection is unclear, because the
      technical ability to detect and quantify it has outpaced studies demonstrating
      its clinical significance. The detection of minimal residual disease most
      consistently has been associated with relapse in acute lymphoblastic leukemia,
      t(15;17) acute myeloid leukemia, and chronic myeloid leukemia post-transplant,
      especially after T-cell depletion. But, in many types of leukemia, including
      acute myeloid leukemia and acute lymphoblastic leukemia, MRD can be detected in
      long-term remission patients without subsequent relapse. The study of MRD is
      evolving from detecting residual disease and predicting relapse to the study of
      the mechanisms that explain how minimum residual disease can coexist in a "cured"
      patient.

PMID- 9260052
TI  - Supportive care in hematologic malignancies, including hematopoietic growth
      factors, transfusions, and infectious complications.
AB  - This review focuses on some of the recent developments in the field of supportive
      care in hematologic malignancies. The increasingly important role of
      hematopoietic growth factors in modern treatment modalities for hematologic
      disorders is clear. Newer developments in transfusional therapy and in the
      management of infectious complications are also discussed.

PMID- 9260053
TI  - Recent advances in the treatment of acute leukemia.
AB  - This review briefly summarizes literature considered noteworthy in the field of
      adult acute leukemia published during 1996. Does intensity remains a
      controversial issue in both acute myelogenous and lymphoblastic leukemia. The
      most convincing data showing efficacy of high dose fractionated chemotherapy was
      presented in patients with Burkitt's lymphoma/leukemia; the remainder of clinical
      studies failed to show a definitive advantage to high-dose therapy. Numerous
      studies addressed the role of the multidrug resistant phenotype and, at least in
      adult disease, demonstrated that the presence of this particular phenotype was a
      poor prognostic indicator. In the pediatric population, the significance of
      multidrug resistance expression appeared less clear. Discrepancies between
      protein expression and function were also evaluated in clinical samples and
      outcomes reported in large clinical series. Among the most interesting scientific
      investigations were those focused on the molecular mechanisms involved in the
      specific translocations t(15;17) and t(8;21) in acute myelogenous leukemia and
      t(12;21) in acute lymphoblastic leukemia. The genes PML and AML1, and ETO were
      examined in normal hematopoietic progenitors and their fusions proteins, PML/RAR
      alpha and AML1/ETO, measured in patients in clinical remission, and important
      data were presented concerning these proteins and measurement of minimal residual
      disease. Provocative data were also presented suggesting that retinoic acid may
      induce synthesis of a protein that selectively degrades PML/RAR alpha, and that
      interferons may regulate PML/RAR alpha expression.

PMID- 9260054
TI  - Myelodysplasia and myeloproliferative disorders.
AB  - Myelodysplasia and the myeloproliferative disorders are clonal hematopoietic stem
      cell disorders with heterogeneous clinical presentations and prognoses. This
      review highlights some of the recent progress that has been made in these
      disorders. Specifically, a number of studies have enhanced our understanding of
      the pathogenesis of these disorders, and potentially useful animal models for
      primary myelofibrosis have been developed. New, clinically useful prognostic
      scoring systems have been devised for myelodysplasia and for primary
      myelofibrosis. New chemotherapeutic approaches and nonmyelosuppressive
      alternative therapies for myelodysplasia have been studied. Data on the use of
      interferon for polycythemia vera and the potential leukemogenesis of hydroxyurea
      have recently become available. Finally, continued progress has been made in the
      use of allogeneic (related and unrelated donor) and autologous stem cell
      transplantation for myelodysplasia.

PMID- 9260055
TI  - Chronic lymphocytic leukemia.
AB  - Much progress has been made over the past year in our understanding of the
      cytogenesis, biology, and therapy of chronic lymphocytic leukemia (CLL). Further
      definition of common cytogenetic abnormalities in CLL make it appear that the
      identification of a new tumor suppressor gene is close at hand. Recent studies
      have also defined relationships between genetic abnormalities and leukemia cell
      phenotype and drug resistance that may assist in assessing prognosis or assigning
      therapy. We have achieved a better understanding of the surface antigens that
      help govern the pattern of tissue infiltration of leukemia cells in vivo. Studies
      of the immune pathophysiology of CLL are providing clues to potential mechanisms
      leading to the autoimmunity and immunodeficiency associated with this disease.
      The efficacy of purine analogues in CLL has been verified in multicenter clinical
      trials. Finally, new therapies incorporating bone marrow transplantation, and
      possibly gene therapy, are being considered more frequently for the therapy of
      patients with this disease.

PMID- 9260056
TI  - Chronic myeloid leukemia.
AB  - The molecular origin of the BCR-ABL chimeric gene is now reasonably well defined;
      a new breakpoint cluster region in the BCR gene, designated mu-bcr, has recently
      been identified. p210BCR-ABL binds with or phosphorylates a wide variety of
      intracellular proteins but the mechanism by which it exerts its oncogenic
      potential is not yet known. Treatment decisions for younger patients are often
      complex. Interferon alfa prolongs life in comparison with conventional cytotoxic
      drugs but the optimal starting dosage, the definition of response, and the
      management of interferon alfa responders remain controversial. Allografting is
      the treatment of choice for younger patients with HLA-identical siblings but its
      precise role for patients lacking such donors is still unclear. The transfusion
      of donor lymphoid cells is very effective in reinducing molecular remission in
      patients who relapse after allografting; the mechanism for this graft-versus
      leukemia effect remains speculative. Autografting with Philadelphia-negative
      progenitor cells appears promising. A working algorithm for the management of
      patients not entered into prospective clinical studies is proposed; such an
      algorithm will need to be updated at frequent intervals.

PMID- 9260057
TI  - Recent advances in the treatment of Hodgkin's disease.
AB  - Most patients who present with Hodgkin's disease today can be cured of their
      disease. Current treatments strive to maintain a high level of efficacy while
      reducing side effects that limit the quality and length of survival.
      Sophisticated molecular techniques continue to aid our understanding of the
      etiology and pathogenesis of this disease. However, the heterogeneity and paucity
      of "malignant" cells in Hodgkin's disease continue to limit our ability to
      articulate a coherent and encompassing model.

PMID- 9260058
TI  - Advances in the treatment of multiple myeloma.
AB  - Conventional chemotherapy for multiple myeloma results in low complete response
      rates, and disease progression usually occurs within a couple of years. High-dose
      chemotherapy with autotransplantation, which has been shown to result in
      encouraging complete remission rates over several years in phase II studies, was
      recently shown in a randomized study to be superior to conventional therapy.
      Eventual tumor recurrence is a problem after autografting, and the development of
      novel maintenance chemotherapy or immunotherapy strategies is necessary to
      eliminate minimal residual disease. Although allogeneic transplantation cures a
      small proportion of patients, high transplant-related mortality and relapse rates
      hamper survival. Development of novel conditioning regimens and means to harness
      the graft-versus-myeloma effect without the associated morbidity of graft-versus
      host disease are necessary to improve success rates. Supportive therapy, mainly
      bisphosphonates to delay progression of bone disease and improve bone density and
      erythropoietin to improve hemoglobin levels, also plays an important role in the
      overall management. This article reviews therapeutic advances in multiple myeloma
      from the 1996 literature.

PMID- 9260059
TI  - Hematologic malignancies.

PMID- 9260060
TI  - Insulin-like growth factors in poultry.
AB  - A large amount of research, primarily in mammals, has defined to a great extent
      the pleiotropic effects of the IGF system on growth, development, and
      intermediary metabolism. Similar elucidations in poultry were hindered to some
      extent by the absence of native peptides (IGF-I and IGF-II) until their
      purification, followed by the production of recombinant chicken IGFs. In many
      ways IGF physiology in birds is similar to that in other species, including but
      not limited to the fact that IGF-I synthesis is both GH- and GH-independent, and
      that autocrine-paracrine IGF action is evident. However, it is clear that several
      unique differences in IGF physiology exist between birds and mammals. For
      example, more IGF is present in the free form in chickens, and the biological
      responses to the IGFs is different in several metabolic pathways in birds
      compared to mammals. To date, no unique IGF-II receptor has been identified in
      birds. Despite an increasing understanding of the IGFs in aves, several important
      questions remain to be answered. What is the role of IGF-II in embryo development
      and posthatch growth? Does an IGF-II receptor entity exist in nonmammalian
      species? How does nutrition affect IGF-I and IGF-II gene expression, and can this
      information be used to enhance poultry production? What is the biochemical
      composition of the IGFBPs, and what are their roles in birds? Can the genetic
      variation present in poultry be used to positively modify IGF gene expression and
      physiology? How do the IGFs regulate intermediary metabolism? What is the role of
      the IGFs in the etiology of several disease states associated with rapid growth
      in poultry, including tibial dyschondroplasia, obesity, ascites, and spiking
      mortality syndrome? Answers to these questions are relevant to our understanding
      of the basic mechanisms of IGF physiology as well as possibly assisting in the
      amelioration of problems found in modern poultry production.

PMID- 9260061
TI  - Serum concentrations of insulin-like growth factors and placental lactogen during
      gestation in cattle. I. Fetal profiles.
AB  - Sixty crossbred beef heifers pregnant with fetuses of either high (H; n = 30) or
      low (L; n = 30) genetic potential for growth were used to establish fetal serum
      profiles of insulin-like growth factor (IGF)-I, IGF-II, and placental lactogen
      (PL), and to examine relationships between serum hormone concentrations and fetal
      growth parameters. Three H and three L fetuses were collected by caesarean
      section at 21-d intervals from Day 85 through Day 274 of gestation. Arterial,
      venous, and mixed umbilical blood samples were collected during surgery. Fetal
      body weight, crown-rump length, hip height, and heart girth were measured. Serum
      concentrations of IGF-I and IGF-II increased (P < 0.0001) with advancing
      gestational age, whereas serum PL declined (P < 0.0001) linearly (P < 0.01)
      throughout gestation. Serum concentrations were greater in the umbilical vein
      compared with the umbilical artery for IGF-II (P < 0.0001) and PL (P < 0.05), but
      not IGF-I. Fetal IGF-I, IGF-II, and PL serum concentrations were not correlated
      with serum concentrations of the respective maternal hormones. Fetal serum IGF-I
      concentrations were correlated to fetal body weight (r = 0.66), growth rate (r =
      0.72), crown-rump length (r = 0.20), hip height (r = 0.17), and heart girth (r =
      0.20). Correlations between fetal serum IGF-II concentrations and the same
      parameters were 0.60, 0.62, 0.39, 0.34, and 0.37, respectively. Fetal serum PL
      concentrations were negatively correlated to body weight (r = -0.40) and growth
      rate (r = -0.40) and not correlated with any fetal linear measure. Fetal genotype
      (L vs. H) differences were detected for IGF-I (P < 0.05) and PL (P = 0.09)
      concentrations. Fetal sex effects were not observed for any hormone. Maternal
      sire breed, hip height, and body condition score did not influence fetal serum
      hormone concentrations.

PMID- 9260062
TI  - Somatotroph function in the neonatal pig.
AB  - The objective of this study was to evaluate developmental changes in somatotroph
      function and related gene expression in neonatal pigs. Male piglets were
      sacrificed at 1, 7, 14, 21, 28, 35, and 42 d of age (8/age group) for the
      collection of tissue and blood. Serum concentrations of GH were determined.
      Quantitations of mRNA were performed for pituitary Pit-1, GH, and GHRH receptor.
      Cultures of pituitary cells from each pig were stimulated with 0, 0.1, 1, or 10
      nM GHRH; 2 mM 8-Br-cAMP; or 100 nM phorbol myristate acetate. Elevated serum
      concentrations of GH were observed at 1 d of age, followed by a pronounced
      decrease to basal levels thereafter (P < 0.0001). A mild transient increase in
      circulating GH occurred at Day 28. In vitro GH secretion was significantly
      stimulated by secretagogue treatments (P < 0.0001). Age-related declines in in
      vitro GH secretion were observed regardless of if the cells were stimulated by
      GHRH or by secretagogues that bypass the GHRH receptor (P < 0.001). Similarly,
      cellular GH content varied with age (P = 0.01). Levels of pituitary GH mRNA (P =
      0.01) and GHRH receptor mRNA (P = 0.0002) decreased with age. The quantity of
      GHRH receptor mRNA was correlated with GH mRNA levels (r = 0.55, P = 0.02), serum
      GH concentrations (r = 0.55, P = 0.02), and in vitro GH secretion (r = 0.66, P =
      0.001). Pituitary Pit-1 mRNA levels at 7 and 14 d of age were significantly
      elevated relative to all other sampling times (P = 0.0002). Levels of Pit-1 and
      GH mRNAs were significantly correlated (r = 0.64, P = 0.003). These results
      demonstrate a strong developmental regulation of somatotrophic function and
      related gene expression during the early neonatal period of the pig. Age-related
      decreases in secretory function may be mediated by concurrent mechanisms relating
      to the expression of the GHRH receptor and of GH.

PMID- 9260063
TI  - Paradoxical increases of circulating nonesterified fatty acids in somatotropin
      treated cattle undergoing mild disturbances.
AB  - Effects of various doses of bovine somatotropin (bST) on plasma concentrations of
      nonesterified fatty acids (NEFA) were studied in a 14-d Latin square with six
      Holstein heifers. Animals were given daily injections of excipient or bST at
      12:00 p.m. and fed twice daily at 7:00 a.m. and 7:00 p.m. On Day 14, plasma NEFA
      remained low through the day except around the 7:00 p.m. feeding when they were
      substantially elevated. The elevation was significantly greater in bST-treated
      animals and corresponded to the excitement of the animals in anticipation of the
      evening feeding. To further investigate this phenomenon, a second experiment was
      conducted in which nine growing Holstein steers were fed hourly and received
      either daily intramuscular (i.m.) injection of excipient or bST (120 mg/kg BW)
      for 15 d in a crossover design. Daily profiles of NEFA were obtained under
      undisturbed conditions or concurrently with intensive handling. Although no
      elevations could be detected in any case in control animals, bST caused a
      substantial rise in NEFA concentration only when animals were subjected to
      intensive handling. This suggested that NEFA peaks noted in bST-treated heifers
      in the first experiment resulted from increased ability of adipose tissue to
      respond to adrenergic stimulation associated with the anticipation of feeding.
      Consistent with this hypothesis, plasma NEFA concentrations in bST-treated steers
      were increased to a greater extent during a challenge involving i.v. injection of
      epinephrine. This amplification of adipose tissue response by bST must be
      considered when conducting intensive studies. Even the minimal excitement
      associated with blood sampling can confound the results regarding lipid
      mobilization, and this may have contributed to the notion that ST is a lipolytic
      hormone.

PMID- 9260064
TI  - Inhibin is involved in the suppression of FSH secretion in the growth phase of
      the dominant follicle during the early luteal phase in cows.
AB  - This study was carried out to examine the involvement of inhibin in the
      regulation of FSH secretion during the growth phase of the dominant follicle in
      the early luteal phase of cows. Six cows were given a single i.v. bolus injection
      of 100 ml inhibin antiserum raised against bovine 32-kDa inhibin in a castrated
      male goat, and five animals received the same amount of castrated male goat serum
      (control serum) on Day 5 of the estrous cycle (Day 0 = estrus). All animals in
      each group experienced a wave of follicular development after ovulation, and the
      dominant follicle was over 8.5 mm in diameter on Day 5. The corpus luteum was
      identified for each group on Day 5. Plasma concentrations of estradiol and
      progesterone gradually increased after ovulation and reached around 3.7 pg/ml and
      3.0 ng/ml on Day 5, respectively, suggesting that the dominant follicle and
      corpus luteum were functional. Administration of inhibin antiserum produced a
      clear increase (P < 0.001) in plasma FSH within 8 hr compared with that in
      control animals. Plasma levels of luteizing hormone showed a moderate increase
      during 40 hr after the injection of antiserum (P = 0.08). A large number of
      antral follicles (4 mm in diameter) developed after the hypersecretion of FSH,
      coupled with the rise in plasma estradiol levels. These results clearly
      demonstrated that inhibin neutralization during the early luteal phase produces
      hypersecretion of FSH with a coincident stimulation of follicular development,
      indicating that inhibin is an important factor for the negative regulation of FSH
      secretion during the early luteal phase when secretion of estradiol and
      progesterone are normally high.

PMID- 9260065
TI  - Punishment alters the discriminative stimulus effects of midazolam.
AB  - Experiment 1 examined the effects of punishment on the discriminative stimulus
      (DS) effects of midazolam (M) and pentobarbital (P) in 3 pigeons. Sessions began
      with a fixed-interval (FI) 3-min schedule of food reinforcement. After 40 min,
      either saline (S) or 0.56 mg/kg of M was injected. A drug-discrimination (DD)
      component began 10 min later. Pecking the left key produced grain after S
      injections, whereas pecking the right key produced grain after M. Dose-response
      curves for M and P were obtained under these conditions and also when every 30th
      peck during the FI was punished by shock. The introduction of punishment
      increased sensitivity to the DS effects of M and P. Experiment 2 examined whether
      a punishment history increases sensitivity to the DS effects of M. After DD
      training and testing, pecking was punished for 10 sessions. This history shifted
      the M dose-response curve to the left for 3 of 4 pigeons. These results emphasize
      the contribution of behavioral variables to the DS effects of drugs.
      Environmental variables appear to play a prominent role in guiding sensitivity to
      the subjective effects of drugs.

PMID- 9260066
TI  - Benzodiazepine-GABA modulation of concurrent ethanol and sucrose reinforcement in
      the rat.
AB  - These experiments examined the role of the benzodiazepine (BZ)-GABA receptor
      complex in modulating ethanol consumption in rats. Lever presses were reinforced
      with concurrently available, isocaloric solutions: 10% ethanol-10% sucrose and
      24% sucrose. Both reinforcers were available on independent, variable-interval 5
      s schedules of reinforcement. In baseline sessions, rats earned approximately 110
      sucrose reinforcers and 131 ethanol-sucrose reinforcers, equivalent to about 2 g
      ethanol per kilogram of body weight. Before experimental sessions, rats received
      injections of Ro 15-4513, Ro 15-1788, and Ro 15-4513 in combination with Ro 15
      4513, chlordiazepoxide, picrotoxin, baclofen, and muscimol. Responding for the
      ethanol solution was significantly and selectively reduced by the BZ inverse
      agonist Ro 15-4513, and this effect was blocked by administration of the BZ
      antagonist Ro 15-1788. Conversely, responding for the ethanol solution increased
      following a low dose of the BZ agonist chlordiazepoxide. A low dose of baclofen
      significantly decreased responding for sucrose and increased consumption of
      ethanol. Picrotoxin and muscimol selectively reduced responding for the ethanol
      solution. These results are discussed in terms of the relationship between the BZ
      GABA receptor complex and ethanol consumption.

PMID- 9260067
TI  - (R)-methanandamide, but not anandamide, substitutes for delta 9-THC in a drug
      discrimination procedure.
AB  - Fourteen male rats were trained to discriminate between injections of 2 mg/kg
      delta-9-tetrahydrocannabinol (delta 9-THC) and vehicle in a 2-lever operant drug
      discrimination paradigm. Following training, substitution tests using a
      cumulative dosing procedure revealed that anandamide (0.5-16 mg/kg ip), the
      putative endogenous camabinoid receptor ligand, failed to generalize to the
      discriminative stimulus properties of the training dose of delta 9-THC. However,
      dose-dependent generalization to the delta 9-THC cue was observed following
      administration of both CP-55,940 (0.05-0.8 mg/kg ip), a synthetic cannabinoid,
      and (R)-methanandamide (0.5-8 mg/kg ip), a metabolically stable analog of
      anandamide. Collectively, these results demonstrate a cannabinoid-specific in
      vivo effect of an anandamide compound and suggest that the naturally occurring
      form of anandamide may be metabolized too rapidly to produce a cannabimimetic
      intercceptive state when administered peripherally.

PMID- 9260068
TI  - Ethanol and pentobarbital: comparison of behavioral and subjective effects in
      sedative drug abusers.
AB  - The behavioral and subjective effects of acute oral doses of placebo, ethanol
      (0.5, 1.0, and 2.0 g/kg), and pentobarbital (150, 300, 600, and 750 mg/70 kg)
      were compared in 8 male volunteers with histories of sedative drug abuse using a
      double-blind, double-dummy, cross-over design. Ethanol and pentobarbital produced
      similar dose-related decrements in psychomotor and cognitive performance and
      exhibited a similar profile of effects on staff- and participant-rated measures.
      There was some evidence indicating that, at the highest dose, pentobarbital was
      perceived by participants as being more sedating than ethanol and that
      pentobarbital has a greater abuse liability than ethanol. In conjunction with the
      results of previous human laboratory studies comparing the effects of different
      types of sedative-hypnotic drugs, these results support a mostly barbiturate-like
      rather than benzodiazepine-like profile of effects for ethanol.

PMID- 9260069
TI  - The expanding indications for clozapine.
AB  - Clozapine is increasingly being used for clinical indications in addition to
      treatment-resistant schizophrenia; this article reviews the relevant literature.
      The first section reassesses the risks associated with clozapine treatment,
      particularly agranulocytosis. The next section discusses its use for
      schizophrenia in patients who are treatment resistant, not treatment resistant,
      and intolerant of traditional drug treatments. Subsequent sections address its
      use in mood disorders, neurologic conditions, comorbid substance abuse,
      aggressive behavior, and childhood schizophrenia. Each includes the initial
      rationale for the use of clozapine in the disorder, a critical evaluation of the
      relevant literature, and theories as to why clozapine's unique pharmacodynamic
      profile may be efficacious for the specific condition. This body of literature
      suggests clozapine may be an effective treatment for a wide range of disorders.

PMID- 9260070
TI  - Effects of abused drugs on psychomotor performance.
AB  - Some abused drugs have been reported to alter performance on naturalistic tasks
      such as driving and also on laboratory tasks. The performance effects of several
      drug classes were examined using a repeated measures design. Eight volunteers
      were administered 2 doses of ethanol, marijuana, amphetamine, hydromorphone,
      pentobarbital, or placebo on separate days. The larger dose of each increased
      subjective drug strength; however, only ethanol and pentobarbital impaired
      performance on circular lights, digit symbol substitution, and serial math tasks.
      Both ethanol and pentobarbital impaired performance on card-sorting tasks;
      impairment was evident at lower doses as the cognitive load increased. Results
      illustrate differences among drugs in producing performance impairment at doses
      that cause subjective effects. Increasing cognitive requirements uncovered
      performance impairment at lower doses.

PMID- 9260071
TI  - Forget "drinking to forget": enhanced consolidation of emotionally charged memory
      by alcohol.
AB  - Social drinkers (42 men, 18-34 years old) participated in a study of the effects
      of alcohol consumption on incidental memory for emotionally salient verbal
      stimuli. Participants rated depressing, elating, and neutral statements while
      sober. Fifteen minutes later they consumed alcohol or active placebo (1.0 or 0.1
      ml/kg) in an environment with minimal retrograde interference. In surprise memory
      testing 24 hr later, when participants were again sober, the alcohol group had
      increased recall across statement type. The alcohol group also had better
      recognition of depressing and elating statements, but recognition of neutral
      statements did not differ between groups. Findings suggest alcohol produced a
      nonspecific enhancement of incidental memory and that alcohol's motivational
      properties were not implicated.

PMID- 9260072
TI  - Resistance to cognitive impairment under alcohol: the role of environmental
      consequences.
AB  - This study showed that cognitive impairment under alcohol is affected by
      environmental factors. Forty male social drinkers were randomly assigned to 4
      groups. Participants practiced a task that measured their rate of information
      processing. Three groups then performed the task under a moderate dose of alcohol
      (0.62 g/kg) and received either an immediate, informative monetary consequence
      (MI); a delayed, uninformative monetary consequence (M); or no consequence (N)
      for maintaining their unimpaired processing rate. A control group (C) performed
      the task without alcohol or any consequence for performance. The processing rates
      of Groups M and N were slower (i.e., impaired) under alcohol than those of Group
      C. In contrast, Group MI displayed no significant reduction in processing rate
      under alcohol (i.e., no impairment). Resistance to the impairing effects of
      alcohol on information processing is enhanced by a rewarding consequence that
      conveys information about the adequacy of performance under the drug.

PMID- 9260073
TI  - Impulsive and self-control choices in opioid-dependent patients and non-drug
      using control participants: drug and monetary rewards.
AB  - Delay discounting was investigated in opioid-dependent and non-drug-using control
      participants. The latter participants were matched to the former on age, gender,
      education, and IQ. Participants in both groups chose between hypothetical
      monetary rewards available either immediately or after a delay. Delayed rewards
      were $1,000, and the immediate-reward amount was adjusted until choices reflected
      indifference. This procedure was repeated at each of 7 delays (1 week to 25
      years). Opioid-dependent participants were given a second series of choices
      between immediate and delayed heroin, using the same procedures (i.e., the amount
      of delayed heroin was that which could be purchased with $1,000). Opioid
      dependent participants discounted delayed monetary rewards significantly more
      than did non-drug-using participants. Furthermore opioid-dependent participants
      discounted delayed heroin significantly more than delayed money.

PMID- 9260074
TI  - Cocaine use can increase cigarette smoking: evidence from laboratory and
      naturalistic settings.
AB  - Two studies examined the effects of cocaine use on cigarette smoking. Study 1 was
      conducted with 10 healthy volunteers under controlled laboratory conditions.
      Participants received double-blind doses of intranasal cocaine HCl (100 mg) or
      placebo in separate sessions, with each being followed by a 3-hr period of
      monitored cigarette smoking. Latency to the first cigarette and the mean interval
      between cigarettes was significantly shorter and the total number of cigarettes
      smoked was greater after cocaine than placebo administration. Study 2 was
      conducted by using urine specimens from 9 ambulatory cocaine-dependent patients.
      Urine cotinine (nicotine metabolite) levels on days when urinalysis testing
      indicated recent cocaine use were compared with levels on days when urinalysis
      testing indicated no recent use. Cotinine levels were significantly higher on
      cocaine-positive days, indicating that cocaine use was associated with greater
      cigarette smoking. Overall results provide evidence that acute cocaine
      administration can increase cigarette smoking.

PMID- 9260075
TI  - Detection of neuropsychological impairment among substance-abusing patients:
      accuracy of the neurobehavioral cognitive status examination.
AB  - The accuracy of the Neurobehavioral Cognitive Status Examination (NCSE) in
      detecting the presence of cognitive impairment among substance-abusing patients
      was examined. The NCSE and the Neuropsychological Screening Battery (NSB), which
      has been shown in previous studies to discriminate reliably between cognitively
      impaired and intact substance-abusing patients, were administered to 51
      detoxified patients. Using participants' performances on the NSB as the criterion
      measure, 22 (43%) were found to be cognitively impaired. The NCSE identified only
      8 of these 22 patients (36%) as being impaired; additionally, 4 of the 29
      patients found to be cognitively intact by the NSB (14%) were classified as
      impaired by the NCSE. Thus, the false-negative rate of the NCSE is too high to
      recommend its use with substance-abusing patients.

PMID- 9260076
TI  - Influence of acute smoking exposure on the subsequent reinforcing value of
      smoking.
AB  - The reinforcing value of smoking (i.e., the degree to which a smoker will work to
      obtain smoking) after varying the magnitude of prior smoke exposure in smokers
      not trying to quit was examined. Eight men and 8 women participated in 5 sessions
      involving manipulation of prior exposure to smoking: 0, 2, 6, or 12 puffs after
      overnight smoking abstinence or ad-lib smoking before the session. After
      exposure, participants engaged in a computer task involving concurrent schedules
      of reinforcement for smoke puffs (16% all trials) versus money (4-64%). Only the
      greatest amount of prior exposure (ad lib) produced a significant reduction in
      subsequent responding for smoke puffs. No exposure condition significantly
      increased responding above that for 0 puffs, indicating no priming effect. By
      contrast, self-report measures of desire to smoke and amount of money
      participants would pay for a cigarette declined sharply with greater prior
      exposure. These measures were correlated only weakly with smoke-reinforced
      responding on the behavioral task, suggesting that subjective versus behavioral
      measures assess different dimensions of smoking's reward value.

PMID- 9260077
TI  - Caffeine self-administration in humans: 1. Efficacy of cola vehicle.
AB  - Eight exclusive cola drinkers in Experiment 1 (mean caffeine intake = 157 +/- 74
      mg/day) and 16 drinkers of both cola and coffee in Experiment 2 (mean caffeine
      intake = 579 +/- 201 mg/day) underwent 6 independent, double-blind weekly trials.
      Each trial began with a randomized cross-over sampling period of 1 day of access
      to noncaffeinated cola and 1 day of access to caffeinated (33 mg/8 oz) cola.
      During the subsequent 1- or 2-day test period, participants had unlimited
      concurrent access to the 2 colas. Reliable caffeine self-administration occurred
      in 2 of 8 participants in Experiment 1 and in 4 of 16 participants in Experiment
      2. Self-reported drowsiness, fatigue, and headache were higher when participants
      received only placebo colas in Experiment 2, but not Experiment 1. Caffeine self
      administration via cola occurs both among people whose primary source of caffeine
      is cola and among those whose primary source of caffeine is coffee.

PMID- 9260078
TI  - Caffeine self-administration in humans: 2. A within-subjects comparison of coffee
      and cola vehicles.
AB  - The reinforcing effects of caffeine ingested in coffee versus cola were studied.
      Eleven participants who drank both coffee and cola (3-10 cups of coffee and 1-6
      cans of cola daily; M = 632 mg caffeine/day) were tested in 4 conditions: cola at
      33 mg/serving (the usual dose), coffee at 33 mg/serving, cola at 100 mg/serving,
      and coffee at 100 mg/serving (the usual dose). Each condition consisted of 6
      double-blind weekly trials. In each trial, participants sampled caffeinated and
      noncaffeinated beverages and then had concurrent access to the 2 beverages.
      Relative use of these beverages was used to assess caffeine reinforcement. Across
      the 4 conditions (24 weeks), reliable caffeine reinforcement occurred in 5
      participants (45%). Caffeine reinforcement did not differ as a function of
      vehicle or serving dose, and no vehicle-dose interactions were found. With both
      cola and coffee at the commonly used doses, self-reported motivation to work was
      greater and drowsiness and laziness smaller with caffeinated than noncaffeinated
      beverages. Results indicate that, among users of both coffee and cola, caffeine
      self-administration and subjective effects occur with both vehicles.

PMID- 9260079
TI  - Alcohol use disorders and neuropsychological functioning in first-year
      undergraduates.
AB  - The relation between alcohol use disorders and neuropsychological functioning was
      examined in 489 first-year undergraduates, approximately half of whom had a
      history of alcoholism in their biological fathers. Factor analyses of 17
      neuropsychological tests and subtests produced the following 5 factors that were
      the basis of subsequent analyses: Language/Verbal Memory, Visuospatial Ability,
      Motor Speed, Booklet Category Performance, and Attention. Participants with
      alcohol use disorders showed deficits in visuospatial ability. Those who had
      alcohol dependence showed deficits in both visuospatial ability and motor speed
      relative to participants who abused alcohol. The differences in
      neuropsychological functioning remained even after several potential confounding
      variables were controlled statistically. Results suggest that alcohol use
      disorders in first-year college students are associated with deficits in
      neuropsychological measures that are not attributable to several potential third
      variable explanations.

PMID- 9260080
TI  - Building community capacity to promote social and public health: challenges for
      universities.

PMID- 9260081
TI  - Culturally specific health care model for ensuring health care use by rural,
      ethnically diverse families affected by HIV/AIDS.
AB  - This article describes the culturally specific health care model (CSHCM). The
      CSHCM can guide health social workers in assessing and intervening with rural,
      ethnically diverse families. Such families require specialized and regular health
      care but generally face many barriers in obtaining that care. The model relies on
      a culturally specific description of the target community, a culturally sensitive
      approach to assessment and intervention, the use of key indigenous providers, and
      interdisciplinary collaboration among providers. The author describes the use of
      the CSHCM as an emergency intervention with eight hard-to-reach families with
      HIV/AIDS in a rural region with an unusually high prevalence of HIV/AIDS.

PMID- 9260082
TI  - Connecting group members through telephone and computer groups.
AB  - Telephone conference calls and computer-assisted groups are innovative means of
      offering health and mental health services. This article reviews the practice
      literature on the use of technology-based groups and presents the results of a
      survey of group practitioners that focused on their experiences with telephone
      and computer groups, their knowledge and comfort levels with these groups, and
      their perspectives on the benefits and problems of using technology in group
      practice. Benefits of using this technology included increased accessibility,
      convenience, and anonymity; problems were decreased cues, technological issues,
      and group process difficulties. Implications of using telephone and computer
      technology for group practice, particularly in health settings, are discussed.

PMID- 9260083
TI  - Mothers' satisfaction with medical care: perceptions of racism, family stress,
      and medical outcomes in children with diabetes.
AB  - Patient satisfaction is an important indicator of medical outcomes. This study
      used an ecological framework to identify sociodemographic, family, and community
      predictors of mothers' satisfaction with their children's medical care and to
      determine the extent to which satisfaction is associated with medical outcomes
      such as adherence to treatment and health status of children with diabetes.
      Although individual demographics have little influence on satisfaction, family
      and community stressors are significant predictors of mothers' satisfaction with
      medical care. Mothers who reported greater perceptions of racism and family
      stress were significantly less satisfied with their children's medical care than
      those from less stressful environments. Mothers' satisfaction with medical care
      was significantly associated with adherence but was not significantly related to
      the children's health status.

PMID- 9260084
TI  - Resilience in adult children of alcoholics: a nonpathological approach to social
      work practice.
AB  - Imperative for social work practice is the need to examine practice frameworks
      that may inadvertently label variations in cultural expression, ways of
      navigating stress and threat of harm or social oppression, or periods of
      reassembly in negative or pathological terms. This article reviews research that
      explored another way of viewing adult children of alcoholics (ACOAs), because of
      the epistemology of pathology that grounds research and practice in the area of
      alcoholism. Using the Differential Resiliency Model (DRM) developed by the
      author, the study examined qualitative data to obtain a nonpathological approach
      to understanding the resilience of ACOAs. The DRM can help practitioners provide
      more timely and appropriate support and services that complement the survival and
      growth needs of individuals and families. A case example illustrates the use of
      the model.

PMID- 9260085
TI  - Educating students for a changing health care environment: an examination of
      health care practice course content.
AB  - Social work educators are confronting new challenges in preparing students for
      health care practice. Given the changing environment in which health care social
      workers practice and the changing nature of practice itself, it is surprising
      that there have been no surveys of health care curricula since the 1980s. This
      study, which is based on an analysis of the outlines for graduate-level health
      care practice courses from 53 accredited schools, attempts to determine what
      students are taught to prepare them for this altered practice environment.
      Content reflective of current practice issues was infrequently included in course
      outlines. Implications for social work education and practice are discussed.

PMID- 9260086
TI  - Universal health care coverage in the United States: barriers, prospects, and
      implications.
AB  - Universal health care coverage has long been a concern for social workers. This
      article examines barriers to and prospects for universal coverage in the United
      States. The article identifies major obstacles to universal coverage, addresses
      current problems with the U.S. health care system, discusses the debate over
      Medicare and Medicaid, and considers possible routes to universal coverage. The
      article also discusses implications for NASW and other supporters of a single
      payer system.

PMID- 9260088
TI  - New concepts in interstitial cystitis.

PMID- 9260087
TI  - America's most cruel xenophobia.

PMID- 9260089
TI  - Change in urethral pressure during voluntary pelvic floor muscle contraction and
      vaginal electrical stimulation.
AB  - The purpose of the study was to compare the effect of voluntary pelvic floor
      muscle (FFM) contraction and vaginal electrical stimulation on urethral pressure.
      Twelve women with genuine stress incontinence, mean age 49.4 years (range 33-66)
      participated in the study. The urethral and bladder pressures were recorded
      simultaneously through a double-lumen 8 Ch catheter. The patients first performed
      three voluntary PFM contractions. Then two electrical stimulators, Conmax and
      Medicon MS 105, 50 Hz, were used in random order. A visual analog scale was used
      to measure pain and discomfort. Pain was reported to mean 6.8, SEM 0.64 (range
      0.7-9.9) and mean 6.1, SEM 0.81 (range 0-9.1) with Conmax and Medicon MS 105,
      respectively. The mean paired difference in favor of voluntary contraction with
      Conmax was -8.0, SD 6.7, P = 0.0067, and with Medicon MS 105 it was -12.2, SD
      5.9, P = 0.0022. The results demonstrated that voluntary PFM contraction
      increased urethral pressure significantly more than did vaginal electrical
      stimulation.

PMID- 9260090
TI  - Bacteriuria in pregnancy: a comparison of Bangladeshi and Caucasian women.
AB  - During a 5-year period all urine culture results from pregnant Caucasian and
      Bangladeshi women booked for confinement at the Royal London Hospital, London,
      UK, were reviewed to determine race-specific rates of bacteriuria. The results
      showed that the overall prevalence of bacteriuria in the Caucasian group was 6.3%
      compared to 2.0% for the Bangladeshi women. Caucasian women were found to be at
      significantly greater risk across all pregnancy outcome and history categories,
      with the greatest risk observed in grand multiparous women (RR: 4.7, 95% CI: 2.8
      8.3). Pregnancies that resulted in preterm delivery showed a strong association
      of bacteriuria in Caucasian women which was not seen in the Bangladeshi women
      (RR: 4.4, 95% CI: 2.0-8.7). The data suggest that Caucasian women have a
      significantly higher prevalence of bacteriuria in pregnancy than their
      Bangladeshi neighbors. Differences in hygiene practices and clothing may explain
      the observed differences in the bacteriuria rates.

PMID- 9260091
TI  - Visual assessment of urethrovesical junction mobility.
AB  - The aim of the study was to compare visual assessment of anterior vaginal wall
      descent with the Q-tip test in evaluating urethrovesical junction mobility. One
      hundred and eleven patients with prolapse and/or urinary incontinence were
      examined in the supine lithotomy position with an empty bladder. Maximum
      straining Q-tip tests and maximum descent of the anterior vaginal wall were
      measured. Using each centimeter of descent as a cutoff value, the sensitivities,
      specificities and positive and negative predictive values were compared to those
      of the Q-tip test. As the cut-off points were moved distally, specificity
      increased at the expense of sensitivity. There was no single cut-off point that
      provided adequate sensitivity and specificity to be clinically useful to replace
      the Q-tip test. It was concluded that visual assessment of anterior vaginal wall
      descent does not provide diagnostic accuracy and acceptable sensitivity and
      specificity to determine urethrovesical junction mobility. Other methods should
      be employed to assess support.

PMID- 9260092
TI  - Collagen injections for genuine stress urinary incontinence: patient selection
      and durability.
AB  - The questions of patient selection parameters and durability of response in the
      use of collagen injections for genuine stress incontinence are addressed. A total
      of 181 women with a mean age of 64 years (range 26-94) underwent collagen
      injections for urethral incompetence. Treatment outcome was determined by a
      change in individual incontinence grades before and after injection. Of the 181
      women 42 (23%) are cured, 94 (52%) are improved and 45 (25%) failed. Follow-up in
      the successful patients, either cured or improved, was a mean of 21 months (range
      4-69) after their last collagen injection. No difference in outcome was seen in
      relation to patient age or pretreatment grade of incontinence. Of the 30 patients
      with bladder instability, 18 (60%) had a favorable outcome. No significant
      difference in outcome was seen in patients with or without hypermobility (P =
      0.2889). Patients with type III incontinence required the largest amount of
      collagen for a successful outcome. The persistence of continence in 78 patients
      who were cured for at least 2 months were plotted on a Kaplan-Meier survival
      curve. The probability of remaining dry without additional collagen was 72% at 1
      year, 57% at 2 years and 45% at 3 years. It was concluded that, collagen
      injection into the urethra is a safe and well-tolerated procedure. Pretreatment
      bladder instability may be an adverse factor. Patients with or without
      hypermobility had equal benefit. Long-term durability was seen. If deterioration
      occurred repeat collagen injections restored success. The current literature is
      reviewed and the use of collagen relative to other treatments is discussed.

PMID- 9260093
TI  - Rectus fascia colpopexy in posthysterectomy vaginal prolapse: analysis of 18
      cases.
AB  - Posthysterectomy prolapse of the vaginal vault is a complicated and uncommon
      occurrence in gynecology. The treatment is surgical and may be either vaginal or
      abdominal. The great variety of techniques described indicates that there is
      disagreement about the ideal route or technique to be used. The authors present
      their experience in surgical correction using colpopexy with rectus abdominal
      muscle fascia.

PMID- 9260094
TI  - Fistula surgery: past, present and future directions.

PMID- 9260095
TI  - Bladder replacement in women: a new experience.
AB  - Bladder replacement in women in a new experience. In this article the authors
      reviewed in a critical way the patho-physiological principles involved in the
      previous male bladder replacement techniques and the results achieved both
      leading to the recent experience of bladder replacement in women. The authors
      present the recent acquirements about pelvic surgical anatomy and postcystectomy
      oncological radicality in female, and the more common surgical techniques for
      building a neobladder in women with the results achieved up to now. They also
      examined the problems arising from this exciting but precocious experience which
      will surely involve the urological community in the future.

PMID- 9260096
TI  - Infectious peritonitis complicating suprapubic catheter removal.
AB  - Peritonitis following suprapubic catheter placement may result from inadvertent
      placement of the drain through the large and small bowel and bladder base. The
      author describes a case of infectious peritonitis which developed after
      suprapubic catheter removal. The patient, underwent suprapubic catheter placement
      after Burch Colposuspension for genuine stress incontinence. The catheter was
      removed with a full bladder after an uneventful postoperative course, but the
      patient subsequently developed acute infectious peritonitis due to extravasated
      urine from the cystostomy site. It was concluded that suprapubic catheters should
      be removed after the bladder is emptied, to prevent this complication. This may
      be most important in patients who void without residual prior to
      epithelialization of the cystostomy site.

PMID- 9260097
TI  - The anterior vaginal wall as an organ for the transmission of active forces to
      the urethra and the clitoris.
AB  - Attention is drawn to the fact that the anterior vaginal wall is not a simple
      mucous membrane but an active organ, with a hammock-like effect on the urethra.
      It also functions during intercourse to transmit the effect of penile
      introduction into the vagina to the clitoris, by stretching the two ligaments
      that insert around its base.

PMID- 9260098
TI  - Glutaraldehyde-containing dentin bonding agents are mutagens in mammalian cells
      in vitro.
AB  - The mutagenic potential of glutaraldehyde-containing dentin bonding agents was
      shown in previous studies using a bacterial gene mutation assay, the Ames test.
      However, current strategies of genotoxicity testing and regulatory requirements
      for the biological evaluation of medical devices recommend a battery of tests
      that indicate induced mutations in prokaryotic and eukaryotic cells. Accordingly,
      the mutagenicity of three glutaraldehyde-containing bonding agents (Syntac
      adhesive, Prisma Universal Bond 3 adhesive, and Gluma 3) was investigated using a
      quantitative mammalian cell gene mutation assay (V79/HPRT test) in the present
      investigation. The materials were extracted in dimethyl sulfoxide (0.1 g/2 mL)
      for 24 h and original extracts were then serially diluted in cell culture medium
      before exposure to V79 cells. Cytotoxic and mutagenic effects were observed with
      identical concentrations of extracts of the different test materials. There was a
      moderate decrease of the number of surviving cells immediately after the end of
      exposure. Mutagenicity at the hprt locus in V79 cells was found with all
      materials tested, and the increases in the absolute numbers of mutants were dose
      dependent. The mutant frequencies were about 15- (Syntac adhesive and Gluma 3) to
      20-fold (Prisma UB3 adhesive) higher than solvent control values. Since other
      substances than glutaraldehyde may be responsible for the mutagenic effects in
      mammalian cells in this study, work is currently in progress to identify the
      individual mutagenic compounds of dentin adhesives and related composite
      materials.

PMID- 9260099
TI  - CD62, thromboxane B2, and beta-thromboglobulin: a comparison between different
      markers of platelet activation after contact with biomaterials.
AB  - The authors examined the modifications of some markers of platelet activation
      after contact with biomaterials. Glycoprotein GMP-140 (CD62) was evaluated by
      flow cytometry; beta-thromboglobulin (beta-TG) and thromboxane B2 (TXB2) were
      determined by radioimmunoassay. Polyethylene terephthalate (PET) induced a
      remarkable platelet adhesion and a significant increase in beta-TG and TXB2, with
      no increase in CD62 on the nonadherent platelets. Pyrolytic carbon-coated PET
      (PC) did not induce platelet adhesion after 15 min of contact, but a significant
      increase in CD62 was detected. After 30 min a significant increase in platelet
      adhesion as well as the release of beta-TG and TXB2 were noted. The increase was
      lower than that observed for uncoated PET, and after 30 min of contact with PC
      the increase no longer was observed.

PMID- 9260100
TI  - Development of tricalcium phosphate/amylopectin paste combined with recombinant
      human transforming growth factor beta 1 as a bone defect filler.
AB  - Tricalcium phosphate (TCP) was combined with amylopectin to form a deliverable
      carrier paste for recombinant human transforming growth factor beta 1 (rhTGF-beta
      1) intended for bone repair applications. Approximately 80% of rhTGF-beta 1 was
      released from the carrier within 24 h following in vitro incubation in serum.
      Full biological activity was maintained, suggesting the growth factor was stable
      in this formulation before and after in vitro release. In vivo efficacy also was
      assessed, in comparison to a sham control group and a placebo-treated group,
      using a rabbit unilateral segmental defect model (1 cm). Radiographs of defect
      sites taken at scheduled intervals and the mechanical testing of treated limbs at
      56 days demonstrated a higher incidence of radiographic bone union, in concert
      with a stronger torque strength, in the rhTGF-beta 1-treated group compared to
      the placebo group. The short duration of the study and the fact that the model
      used was not a critical defect may account for the lack of superiority of the
      rhTGF-beta 1-treated group over the healing of the sham control. The in vivo
      pharmacokinetics of the growth factor evaluated in the same rabbit model
      suggested that rhTGF-beta 1 persisted intact at the defect site for more than 21
      days. Gamma imaging and radioactivity recovery at defects administered to [131I]-
      and [125I]-labeled rhTGF-beta 1, respectively, estimated the half-life of rhTGF
      beta 1 eliminated from the applied site to be 4-6 days. The present report
      substantiates the potential of rhTGF-beta 1 and its carrier for treatment of bone
      defects.

PMID- 9260101
TI  - Effects of magnesium on the formation of calcium-deficient hydroxyapatite from
      CaHPO4.2H2O and Ca4(PO4)2O.
AB  - Calcium-deficient hydroxyapatite (HA) with a Ca/P molar ratio of 1.50 was
      synthesized in various concentrations (0.01-75 mM) of MgCl2 at 37.4 degrees C by
      reaction between particulate CaHPO4.2H2O and Ca4(PO4)2O. The effects of magnesium
      on the kinetics of HA formation were determined using isothermal calorimetry. All
      reactions completely consumed the precursor phases as indicated by X-ray
      diffraction analysis and a constant enthalpy of reaction (240 kJ/mol). Magnesium
      concentrations below 1 mM had no effect on the kinetics of HA formation.
      Magnesium concentrations between 1 and 2.5 mM affected the reaction path but did
      not affect the time required for complete reaction. Higher concentrations
      extended the times of complete reaction due to magnesium adsorption on the
      precursor phase(s) and HA nuclei, and stabilization of a noncrystalline calcium
      phosphate (NCP). HA formation in the presence of magnesium resulted in separation
      of the following two events: initial formation of HA nuclei and NCP, and
      consumption of CaHPO4.2H2O. This was indicated by the appearance of an additional
      calorimetric peak. Variations in calcium, magnesium, and phosphate concentrations
      and pH with time were determined. Increasing the magnesium concentration resulted
      in elevated calcium concentrations. After an initial decrease in magnesium owing
      to its adsorption onto HA nuclei and precursor(s), a period of slow reaction at
      constant magnesium concentration was observed. Both the magnesium concentration
      in solution and the proportions of precursors present decreased prior to any
      evidence of a crystalline product phase. This is attributed to the formation of
      NCP capable of incorporating magnesium. This noncrystalline phase persisted for
      more than 1 year for reactions in magnesium concentrations about 2.5 mM. Its
      conversion to HA resulted in the release of magnesium to the solution.

PMID- 9260102
TI  - Osseointegration in cortical sheep bone of calcium phosphate implants evaluated
      by PIXE method and histology.
AB  - Osseointegration of porous calcium phosphate ceramics evolves in several stages
      once implanted. Histologic analysis has often been used to evaluate the mechanism
      of integration of this material. Histologic parameters can be completed by
      physical analysis to obtain a semiquantitative evaluation of the osseointegration
      process. The histologic observation of hydroxyapatite (HA)-ceramic-containing
      bone sections was associated with proton-induced X-ray emission (PIXE) analysis
      and the results obtained by both methods were compared. Porous HA-ceramic
      cylinders were implanted in cortical bone of sheep femurs for periods ranging
      from 2 to 36 weeks. Thick sections of the implant containing bone were made at
      the end of the implantation period. A scanning line with two proton impacts 0.5
      mm apart was plotted from the edges of cortical bone across the implanted ceramic
      and the X-rays produced were determined. Calcium, phosphorus, zinc, strontium,
      and iron contents were measured. Following PIXE analysis, the sections were
      surface-stained and observed under a light microscope to define the
      osseointegration index. Two regions of the curves were identified for each
      element characterizing either the bone tissue or the ceramic. Zinc and strontium
      present in the bone tissue but absent from the ceramics appeared after the 8th
      and the 12th implantation weeks, respectively. Iron present in the implant
      decreased with time, and calcium and phosphorus contents tended to be the same at
      the end of the implantation period in both curve regions. Histologic observation
      showed that immature bone invaded the pores of the outer layer of the ceramic as
      early as 2 weeks after implantation. Ceramics were totally osseointegrated 20
      weeks after implantation. Osseointegration was apparently still evolving as
      judged by the PIXE method when histologic integration was considered complete.

PMID- 9260104
TI  - Evaluation of cellular proliferation on collagenous membranes.
AB  - Collagenous membranes are used in guided tissue regeneration designed to repair
      damage done to the periodontium by disease. The cells primarily responsible for
      the process are desmodontal fibroblasts. We have studied the behavior and
      proliferation of fibroblasts grown on collagenous membrane. Fibroblasts grown on
      plastic served as control. Cellular proliferation was evaluated using a
      colorimetric test for cytotoxicity and by flow cytometry. Scanning electron
      microscopy was used to observe cellular morphology. Results showed a reduction in
      cell number, together with a modification in cell cycle, but good preservation of
      cellular morphology for cultures grown on collagenous membrane. These results
      support the in vivo use of collagenous membrane in guided tissue regeneration.

PMID- 9260103
TI  - Adhesion of bacteria to stainless steel and silver-coated orthopedic external
      fixation pins.
AB  - Bacterial adhesion to silver-coated orthopedic external fixation pins was
      compared with stainless steel controls in an in vitro study. Using five bacterial
      isolates from wound infections, the silver coating was found to reduce adhesion
      for Escherichia coli, Pseudomonas aeruginosa, and two strains of Staphylococcus
      aureus while the converse applied for Staphylococcus haemolyticus. When placed in
      human serum, both surfaces were conditioned to a similar extent with serum
      proteins; this conditioning lead to further reductions in bacterial adhesion,
      ultimately approaching similar levels for both stainless steel and silver-coated
      samples.

PMID- 9260105
TI  - Long-term evaluation of degradation and foreign-body reaction of subcutaneously
      implanted poly(DL-lactide-epsilon-caprolactone).
AB  - The aim of this study was to evaluate the degradation and foreign-body reaction
      of poly(DL-lactide-epsilon-caprolactone) (PLA85CL50) bars. This specific
      biomaterial is used for the construction of nerve guides, which can be used in
      the reconstruction of short nerve gaps. Subcutaneously implanted PLA85CL50 bars
      were harvested after implantation periods ranging from 3 to 12 months and
      evaluated for the rate of degradation and the degree of foreign-body reaction. It
      was observed that this copolymer degraded completely within 12 months and that no
      lactide or epsilon-caprolactone crystals were formed. Furthermore, we conclude
      that the foreign-body reaction of PLA85CL50 is very mild. These properties make
      the amorphous copolymer of DL-lactide and epsilon-caprolactone (50:50) suitable
      for the construction of nerve guides.

PMID- 9260106
TI  - Culture materials affect ex vivo expansion of hematopoietic progenitor cells.
AB  - Ex vivo expansion of hematopoietic cells is important for applications such as
      cancer treatment, gene therapy, and transfusion medicine. While cell culture
      systems are widely used to evaluate the biocompatibility of materials for
      implantation, the ability of materials to support proliferation of primary human
      cells in cultures for reinfusion into patients has not been addressed. We
      screened a variety of commercially available polymer (15 types), metal (four
      types), and glass substrates for their ability to support expansion of
      hematopoietic cells when cultured under conditions that would be encountered in a
      clinical setting. Cultures of peripheral blood (PB) CD34+ cells and mononuclear
      cells (MNC) were evaluated for expansion of total cells and colony-forming unit
      granulocyte monocyte (CFU-GM; progenitors committed to the granulocyte and/or
      monocyte lineage). Human hematopoietic cultures in serum-free medium were found
      to be extremely sensitive to the substrate material. The only materials tested
      that supported expansion at or near the levels of polystyrene were tissue culture
      polystyrene, Teflon perfluoroalkoxy, Teflon fluorinated ethylene propylene,
      cellulose acetate, titanium, new polycarbonate, and new polymethylpentene. MNC
      were less sensitive to the substrate materials than the primitive CD34+
      progenitors, although similar trends were seen for expansion of the two cell
      populations on the substrates tested. CFU-GM expansion was more sensitive to
      substrate materials than was total cell expansion. The detrimental effects of a
      number of the materials on hematopoietic cultures appear to be caused by protein
      adsorption and/or leaching of toxins. Factors such as cleaning, sterilization,
      and reuse significantly affected the performance of some materials as culture
      substrates. We also used PB CD34+ cell cultures to examine the biocompatibility
      of gas-permeable cell culture and blood storage bags and several types of tubing
      commonly used with biomedical equipment. While many of the culture bag materials
      gave satisfactory results, all of the tubing materials severely inhibited total
      cell and CFU-GM expansion. Taken together, our results show that many materials
      approved for blood contact or considered biocompatible are not suitable for use
      with hematopoietic cells cultured in serum-free medium. As hematopoietic cultures
      are scaled up for a variety of clinical applications, it will be essential to
      carefully examine the biocompatibility of all materials involved.

PMID- 9260107
TI  - Effect of in vivo and in vitro degradation on molecular and mechanical properties
      of various low-molecular-weight polylactides.
AB  - The in vivo and in vitro degradation of low-molecular-weight poly(L-lactide),
      poly(L/D-lactide), and poly (L/DL-lactide) rods was investigated. The low
      molecular-weight fast-degrading materials were used to accelerate the degradation
      process and make the test conditions more critical. In the in vivo study the rods
      were implanted in the soft tissue of sheep and explanted at 1, 3, 6, and 12
      months. In the in vitro experiments the samples were subjected to aging at 37
      degrees C in the phosphate buffer using two different modes. In the so-called
      pseudodynamic mode the aging buffer was regularly replaced if the pH dropped more
      than 0.5. In the static mode the buffer was not changed over the whole testing
      period of 52 weeks. The mechanical, molecular, and crystalline properties of the
      rods were measured and their appearance in the course of aging was evaluated
      using scanning electron microscopy. It was found that the changes in the
      mechanical properties of poly(L-lactide), poly(L/D-lactide), and poly(L/DL
      lactide) samples subjected to in vitro degradation tests in both the static and
      pseudodynamic modes are in good approximation with data obtained from the in vivo
      study. The pH of the buffer solution had no evident effect on the mechanical
      properties or the rate of degradation as estimated from the drop in molecular
      weight of the aged samples. The replacement of the aging buffer to maintain a
      constant pH at 7.4 does not seem to be critical for the degradation of the
      polylactides. In vitro degradation tests can be used as a relevant procedure for
      predicting the in vivo functionality of implants from the polylactides used if
      the criteria for assessing such a functionality are the changes in mechanical
      properties and molecular weight.

PMID- 9260108
TI  - Biocompatibility of alumina ceramic and polyethylene as materials for pivot
      bearings of a centrifugal blood pump.
AB  - The double pivot bearings in the Gyro C1E3 centrifugal blood pump incorporate a
      high-purity alumina (Al2O3) ceramic and an ultra-high-molecular-weight
      polyethylene (UHMWPE). This centrifugal pump has been developed as a completely
      sealless pump for long-term usage. The combination of Al2O3 and UHMWPE are the
      materials of choice for the acetabular bearing in artificial joints, which have
      proven to be clinically reliable for over 10 years. Previous studies have
      examined the biocompatibility of Al2O3 and UHMWPE as bulky implant materials. The
      present study investigated this material as a blood-contacting material using a
      standard assessment in vitro and in vivo analysis. The examined items were
      systemic toxicity, sensitization (guinea pig maximization test), cytotoxicity
      (elution test), mutagenicity (Ames test), direct contact hemolysis, and
      thrombogenicity. The studies were performed according to the United States
      Pharmacopoeia and published previous studies. The samples of both Al2O3 and
      UHMWPE demonstrated no differences from the negative controls in all tests. These
      findings indicate that both Al2O3 and UHMWPE are biocompatible materials for
      double-pivot bearings in the centrifugal blood pump.

PMID- 9260109
TI  - Mechanism of adsorption of human albumin to titanium in vitro.
AB  - Our previous studies have shown that human albumin is one of the main salivary
      proteins that adsorb to titanium (Ti). The goal of the present study was to
      investigate the role of electrostatic interactions in the adsorption of human
      albumin to Ti-oxide (TiO2) in vitro. The binding profile of human albumin to Ti
      was analyzed according to an adsorption isotherm. Purified human serum albumin
      (HSA) was suspended with native, calcium-, magnesium-, or potassium-treated
      commercially pure Ti powders, at pH 3.0 and 7.0. The amount of unadsorbed protein
      in the supernatant fluid was measured. The maximum amount of adsorbed albumin was
      0.13 mg/1.0 g Ti. The albumin-Ti association constant was 2.77 mL/mg.
      Pretreatment of Ti with calcium, or magnesium alone, or combined with increasing
      pH values (3.0-7.0) resulted in augmented adsorption of HSA to Ti. No increase in
      adsorption was observed following pretreatment of Ti with potassium. These
      results point to the involvement of electrostatic interactions in the adsorption
      of HSA to TiO2.

PMID- 9260110
TI  - Non-decay type fast-setting calcium phosphate cement: hydroxyapatite putty
      containing an increased amount of sodium alginate.
AB  - A hydroxyapatite [(HAP) Ca10(PO4)6(OH)2] putty that behaves like a putty or self
      curing resin was made by increasing the amount of sodium alginate in non-decay
      type fast-setting calcium phosphate cement (nd-FSCPC). nd-FSCPC became viscous as
      the sodium alginate concentration was increased. The best handling properties
      were obtained when nd-FSCPC contained 8% sodium alginate in its liquid phase.
      When a 2-kg glass plate was placed on the paste, HAP putty spread to form an area
      three times that of FSCPC paste. Thus, HAP putty is expected to be easier to use
      than FSCPC in the filling of bone defects. HAP putty did not decay; in fact, it
      set within approximately 20 min when immersed in distilled water immediately
      after mixing. The wet diametral tensile strength value of HAP putty was
      approximately 12 MPa after 24 h, the same as that for nd-FSCPC containing 0.5%
      sodium alginate in its liquid phase, or FSCPC that is free from sodium alginate.
      The elements constituting set HAP putty were examined using powder X-ray
      diffraction and found to be predominantly apatitic minerals after 24 h. Since the
      handling properties of a putty or self-curing resin-like cement are very useful
      in certain surgical procedures, HAP putty made by increasing the sodium alginate
      concentration in nd-FSCPC is potentially a valuable new biomaterial for use in
      plastic and reconstructive surgery, as well as oral and maxillofacial surgery.

PMID- 9260111
TI  - Tumor necrosis factor-alpha and interleukin-6 release from white blood cells
      induced by different graft materials in vitro are affected by pentoxifylline and
      iloprost.
AB  - Inflammatory mediators such as cytokines produced by white blood cells (WBCs) at
      the site of implantation are important for the biocompatibility of vascular
      grafts. The aim of the present study was to demonstrate the tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) release from WBCs incubated with
      expanded polytetrafluoroethylene (ePTFE) or woven Dacron grafts. In a second
      series the effects of pentoxifylline (PTX) and iloprost (ILO), both known to
      inhibit white blood cell function, on this release were determined. Woven Dacron
      grafts induced significantly higher release of both TNF-alpha and IL-6 compared
      to ePTFE. TNF-alpha was detectable first after 2 h, whereas IL-6 was seen after 4
      h. Maximum values were reached at 6 and 12 h, respectively. The addition of an
      endotoxin gave more pronounced patterns of cytokine release not influenced by
      time. Preincubation with both PTX and ILO at final concentrations of 100 and 10
      micrograms/mL, respectively, reduced significantly the TNF-alpha release without
      differences between the two graft materials, whereas the effect on the IL-6
      release varied and was graft material-dependent. In conclusion, graft material
      dependent induction of TNF-alpha and IL-6 from WBCs was demonstrated. PTX and ILO
      influenced the cytokine release. It might be suggested that graft material
      induced cytokine production could contribute to intimal hyperplasia in vivo. The
      present findings encourage further studies regarding graft material-induced WBC
      alterations and the role of pharmacologic agents influencing this function.

PMID- 9260112
TI  - Biodegradation of a poly(ester)urea-urethane by cholesterol esterase: isolation
      and identification of principal biodegradation products.
AB  - Synthesized poly(ester)urea-urethanes with 14C-labeled toluene diisocyanate or
      14C-labeled chain extender ethylene diamine were incubated with cholesterol
      esterase in a phosphate buffer solution at 37 degrees C. A number of
      biodegradation products, generated at the level of 2.8 micrograms/cm2 of polymer
      surface area, were isolated from this simulated physiologic system. Individual
      products were obtained by separation with reversed-phase high-performance liquid
      chromatography. The two different radiolabels were used to assist in the
      identification of degradation products from hard- and soft-segment domains.
      Approximately 20 degradation products were isolated; however, toluene diamine
      (TDA) was not detected from the chromatographic separation. Two principal
      products were identified by tandem mass spectrometry. Both products are TDA
      derivatives (secondary aromatic diamine) substituted with end units of the
      polyester segment at N and N' positions of TDA. The absence of free TDA suggests
      that there could be a stabilization of urethane and urea linkages within the
      toluene diisocyanate (TDI) segments of the polyurethanes. For TDI-synthesized
      polymers, this finding raises awareness to the potential biological importance of
      degradation products other than TDA, particularly to their interaction with
      surrounding cells.